PMID- 17268683 TI - Effects of molecular conformation on inner-shell ionization energies. AB - Experimental evidence for an effect of molecular conformation on inner-shell ionization energies has been observed for the first time. Examples are seen in the carbon 1s spectra of butyronitrile, 1-fluoropropane, and propanal, and other similar molecules. At room temperature these exist in two different conformations, with different distances and, hence, different Coulombic interactions between the negatively charged electronegative group and the methyl carbon. The experimental results are in accord with theoretical predictions with respect to both ionization energies and populations of the different conformers. PMID- 17268684 TI - Electronic properties of Ag nanoparticle arrays. A Kelvin probe and high resolution XPS study. AB - The electronic properties of citrate stabilised Ag nanoparticles with sizes ranging from 4 to 35 nm were investigated by the Kelvin probe method and high resolution XPS. Two and three dimensional assemblies of the particles were prepared by electrostatic adsorption from aqueous solution onto poly-l-lysine modified surfaces. The work function of the Ag particles increased from 5.29 +/- 0.05 to 5.53 +/- 0.05 eV as the particle size decreased. These values are approximately 0.8 eV higher than for clean polycrystalline Ag surfaces. The origin of these remarkable high work functions cannot be explained in terms of either citrate induced changes in the surface dipole or image forces in the confined metallic domains. High resolution XPS spectra of the Ag 3d(5/2) core level were characterised by broad bands and a 0.4 eV shift towards lower binding energies for the smallest particles. Comparisons with reported studies on extended Ag surfaces indicate that as-grown particles exhibit partially oxidised surfaces. The behaviour of the work function further suggests that the strength of the Ag-O bonding increases with decreasing particle sizes. These findings are highly relevant to the interpretation of the catalytic properties of Ag nanoparticles. PMID- 17268685 TI - Bond-formation versus electron transfer: C-C-coupling reactions of hydrocarbon dications with benzene. AB - The bimolecular reactions of several hydrocarbon dications C(m)H(n)(2+) (m = 6 10, n = 4-9) with neutral benzene are investigated by tandem mass spectrometry using a multipole instrument. Not surprisingly, the major reaction of C(m)H(n)(2+) with benzene corresponds to electron transfer from the neutral arene to the dication resulting in the pair of monocationic products C(m)H(n)(+) + C(6)H(6)(+). In addition, also dissociative electron transfer takes place, whereas proton transfer from the C(m)H(n)(2+) dication to neutral benzene is almost negligible. Interestingly, the excess energy liberated upon electron transfer from the neutral arene to the C(m)H(n)(2+) dication is not equally partitioned in the monocationic products in that the cations arising from the dicationic precursor have a higher internal energy content than the monocations formed from the neutral reaction partner. In addition to the reactions leading to monocationic product ions, bond-forming reactions with maintenance of the two fold charge are observed, which lead to a condensation of the C(m)H(n)(2+) dications with neutral benzene under formation of intermediate C(m+6)H(n+6)(2+) species and then undergo subsequent losses of molecular hydrogen or neutral acetylene. This reaction complements a recently proposed dicationic route for the formation of polycyclic aromatic hydrocarbons under extreme conditions such as they exist in interstellar environments. PMID- 17268686 TI - Slab model studies of water adsorption and decomposition on clean and X- (X = C, N and O) contaminated Pd(111) surfaces. AB - To explore the effect of surface contaminants on water chemistry at metallic surfaces, adsorption and decomposition of water monomers on clean and X/Pd(111)(X = C, N and O) surfaces are investigated based on density functional theory calculations. It is revealed that H(2)O binds to Pd(111) surface primarily through the mixing of its 1b(1) with the Pd 4d(z(2)) state. A charge accumulation between the oxygen atom of water and the bound Pd atom is calculated, which is found to be relevant to the H(2)O-Pd interaction. Water adsorption results in a reduction of surface work function and the polarization of the X 2p states. The O H bond scission of H(2)O on the clean Pd(111) is an energy unfavorable process. In the case of X-assisted O-H bond breaking on X/Pd(111) surfaces, however, the reaction barrier tends to be lower than that on the clean surface and decreases from C/Pd(111) to O/Pd(111). In particular, water decomposition is found to become feasible on O/Pd(111), in agreement with the experimental observations. The calculated barrier is demonstrated to be correlated linearly with the density of X 2p states at the Fermi level. A thorough energy analysis demonstrates that the following geometrical and electronic factors favor the barrier reduction on X/Pd(111) with respect to water decomposition on clean Pd(111): (i) the less deformed structure of water in TS; (ii) the decreased bonding competition between the fragments OH and H. The remarkable decrease of the barrier on O/Pd(111) is revealed to be due to the largest stabilization of the split H atom and the least deformation of water in the TS. PMID- 17268687 TI - Efficiencies of state and velocity-changing collisions of superthermal CN A(2)Pi with He, Ar, N(2) and O(2). AB - Polarized laser photolysis of ICN is combined with saturated optical pumping to prepare state-selected CN Alpha(2)Pi (nu' = 4, J = 0.5, F(2), f) with a well defined anisotropic superthermal speed distribution. The collisional evolution of the prepared state is observed by Doppler-resolved Frequency Modulated (FM) spectroscopy via stimulated emission on the CN Alpha(2)Pi-Chi(2)Sigma(+) (4,2) band. The phenomenological rate constants for removal of the prepared state in collisions with He, Ar, N(2) and O(2) are reported. The observed collision cross sections are consistent with attractive forces contributing significantly for all the colliders with the exception of He. The collisional evolution of the prepared velocity distribution demonstrates that no significant back-transfer into the prepared level occurs, and that any elastic scattering is strongly in the forward hemisphere. PMID- 17268688 TI - Stabilisation energy of C(6)H(6)...C(6)X(6) (X = F, Cl, Br, I, CN) complexes: complete basis set limit calculations at MP2 and CCSD(T) levels. AB - Stabilisation energies of stacked structures of C(6)H(6)...C(6)X(6) (X = F, Cl, Br, CN) complexes were determined at the CCSD(T) complete basis set (CBS) limit level. These energies were constructed from MP2/CBS stabilisation energies and a CCSD(T) correction term determined with a medium basis set (6-31G**). The former energies were extrapolated using the two-point formula of Helgaker et al. from aug-cc-pVDZ and aug-cc-pVTZ Hartree-Fock energies and MP2 correlation energies. The CCSD(T) correction term is systematically repulsive. The final CCSD(T)/CBS stabilisation energies are large, considerably larger than previously calculated and increase in the series as follows: hexafluorobenzene (6.3 kcal mol(-1)), hexachlorobenzene (8.8 kcal mol(-1)), hexabromobenzene (8.1 kcal mol(-1)) and hexacyanobenzene (11.0 kcal mol(-1)). MP2/SDD** relativistic calculations performed for all complexes mentioned and also for benzene[dot dot dot]hexaiodobenzene have clearly shown that due to relativistic effects the stabilisation energy of the hexaiodobenzene complex is lower than that of hexabromobenzene complex. The decomposition of the total interaction energy to physically defined energy components was made by using the symmetry adapted perturbation treatment (SAPT). The main stabilisation contribution for all complexes investigated is due to London dispersion energy, with the induction term being smaller. Electrostatic and induction terms which are attractive are compensated by their exchange counterparts. The stacked motif in the complexes studied is very stable and might thus be valuable as a supramolecular synthon. PMID- 17268689 TI - Redistribution of emitting state population in conjugated polymers probed by single-molecule fluorescence polarization spectroscopy. AB - Fluctuations in the fluorescence polarization degree and direction are reported for the first time for single conjugated polymer molecules embedded in a polystyrene matrix at room temperature. The polymer molecule, a polythiophene derivative, clearly emits as a multi-chromophore ensemble showing that the energy does not funnel to any specific low-energy trap. The fluorescence instead originates from thermally populated exciton states with different relative orientations of the transition dipole moments. The fluctuations in the fluorescence polarization are explained in terms of changes in the relative contributions of the different exciton states to the signal due to conformational fluctuations of the molecule or selective exciton quenching by triplet states. PMID- 17268690 TI - Role of descending venography and endovenous embolization in treatment of females with lower extremity varicose veins, vulvar and posterior thigh varices. AB - OBJECTIVE: To evaluate the prevalence of refluxing pelvic veins among female patients with lower extremity varicose veins and the role of embolization treatment in these cases. METHODS: Of 158 female patients suffering from primary varicose veins of the lower extremities presented to the Venous Disease Clinic at Dhahran Health Center between January 2002 and December 2004, 25 patients (15.8%) were noted to have vulvar or postero-medial thigh varices or both. Those were referred for trans-jugular descending pelvic venography with or without subsequent embolization of the contributing refluxing veins. RESULTS: Venous reflux contributing to the vulvoperineal or posterior thigh varices was detected in 23 patients (92%) on catheter venography. Left ovarian venous reflux was responsible for 60% of all cases. Embolization, using multiple coils, was successful in 18 patients with positive reflux (78.3%). One patient had primary vulvar venous malformation that required additional percutaneous sclerotherapy using dehydrated ethanol. Four patients had femoro-saphenous reflux contributing to the varices and required subsequent surgical ligation excision. All treated cases showed significant improvement of their symptoms without any procedure related complications. CONCLUSION: In patients with vulvar or postero-medial thigh varicose veins, radiological study of ovarian and hypogastric venous reflux should be considered. Trans-jugular descending venography and embolization is a feasible, effective and safe diagnostic and therapeutic modality. PMID- 17268691 TI - Antibacterial activity of Elaeagnus umbellata (Thunb.) a medicinal plant from Pakistan. AB - OBJECTIVE: To evaluate the biological activity of Elaeagnus umbellata extracts on standard microorganism strains as well as multi-drug resistant bacteria isolated from hospitals. METHODS: We carried out this study at the Plant Pathology Laboratory of the University College of Agriculture, Rawalakot Pakistan during the period between September-November 2004. Flowers, leaves, and berries of the plant were extracted in different solvents and tested for their antibacterial activity by disc diffusion method on selected organisms like methicillin resistant Staphylococcus aureus (S. aureus), multi-drug resistant Pseudomonas aeruginosa (P. aeruginosa), and enterohemorrhagic Escherichia coli (E. coli). RESULTS: The ether extract of flower was found to be highly effective against E. coli, P. aeruginosa, S. aureus, and Bacillus subtilis (B. subtilis). The alcohol extract of these leaves also demonstrated strong activity against gram positive and negative bacteria. The aqueous extract from the berry strongly inhibited the growth of E. coli and S. aureus whereas, it exhibited a very small zone of inhibition against B. subtilis. Multi-drug resistant P. aeruginosa was found completely resistant to aqueous extract. The acetone extract of the berry showed good activity against P. aeruginosa. CONCLUSION: The present study reports the antibacterial activity of Elaeagnus umbellata. Most of the extracts displayed broad-spectrum activity, since gram positive bacteria including S. aureus, B. subtilis and gram-negative bacteria including E. coli and P. aeruginosa were inhibited. These preliminary findings may provide the basis for traditional use of this plant in the treatment of infectious diseases. PMID- 17268692 TI - Computed tomography and ultrasonography in the diagnosis of equivocal acute appendicitis. A meta-analysis. AB - Acute appendicitis is the most common acute surgical condition of the abdomen. Computed tomography (CT) and Ultrasonography (US) can reduce the rate of complications and unnecessary appendectomies, in addition, they can establish an alternative diagnosis. We carried out a systematic review to evaluate the evidence relating radiological imaging (US and CT scan) and early detection of acute appendicitis in patients presenting with equivocal findings, and to provide recommendations to use radiological imaging (US and CT scan) in diagnosing acute appendicitis as part of the initial clinical assessment of the patients presenting with equivocal findings to reduce complications and unnecessary appendectomies. We used the MEDLINE to search for articles published from 1966 to December 2005 that related to radiological imaging of acute appendicitis; additional articles were identified from the bibliographies of review articles. Selection criteria were used to limit the analysis to prospective studies with more than 100 patients involved in each study as a study group. Forty-five studies fulfilling our inclusion and exclusion criteria were extracted, and 13,046 patients were included. Although the CT scan was more sensitive than US in diagnosing patients with equivocal appendicitis (93.4% [95% CI 92.1-94.6] versus 83.7% [95% CI 82.3-85.0]), either diagnostic study should be used as part of the initial assessment of the patients presenting with equivocal findings. PMID- 17268693 TI - Effect of basic fibroblast growth factor on cardiomyocyte differentiation from mouse embryonic stem cells. AB - OBJECTIVE: To investigate the effect of basic fibroblast growth factor (bFGF) on the differentiation of embryonic stem cells (ESCs) into early cardiomyocytes. METHODS: Embryoid bodies (EBs) were produced from mouse ESC line (Royan B1) in hanging drops and cultured for 5 days as suspension. During the first 2 days of suspension, the EBs of the experimental group were treated with 10 ng/ml of bFGF and subsequently plated onto gelatin-coated tissue culture dishes (day 7). The differentiated cells were evaluated pharmacologically, by immunocytochemistry, and so forth. The study was carried out in the Department of Stem Cells, Royan Institute, Tehran, Iran in 2005. RESULTS: The beating frequency in the bFGF treated EBs was less than that in the control group. In addition, the beating in the EBs of the experimental group, treated with isoprenaline and phenylephrine, was only more than 7+3 days in comparison to the control group. The response of the EBs to carbachol was more in the bFGF group than 7+14 days. In all the stages of development, the beating cells in the EBs of both groups expressed beta actinin, myosin light chain isoform 2V, cardiac alpha-myosin heavy chain (alpha MHC), and cardiac beta-myosin heavy chain (beta-MHC). Nonetheless, during 7+3 days, the last 2 genes were more advanced in the bFGF group. The atrial natriuretic factor was also expressed at a late stage in both groups. CONCLUSION: Basic fibroblast growth factor can only promote the early maturation of ESC derived cardiomyocytes in terms of chronotropic characteristics and expression of cardiac alpha-MHC and beta-MHC. PMID- 17268694 TI - Cytogenetic studies in amenorrhea. AB - OBJECTIVE: To study the frequency of the chromosomal abnormality (CA), referred for karyotyping, and counseling in individuals with primary amenorrhea (PA) and secondary amenorrhea (SA). METHODS: We report on a retrospective survey of 865 women with amenorrhea (620-PA and 245-SA) at the Division of Human Genetics, Department of Anatomy, St. John's Medical College, Bangalore, India from 1973 to 2005. RESULTS: The frequency of the CA in amenorrhea was 23.35%, while PA was 26.13%, and SA was 16.33%. Numerical CA was prevalent in 45.54% of the total; 43.83% in PA, and 52.5% in SA. In numerical chromosomal abnormality, the observed karyotypes were: 45,X; 47,XXX; X mosaicism (45,X/46,XX; 45,XX/46,XX/47,XXX; 45,X/47,XXX; 46,XX/47,XXX); Y mosaicism (45,X/46,XY; 45,X/47,XYY); and others: 46,XX/47,XX+10; 46,XX/46,XY; 46,XX/47,XXY. In addition, is the presence of 46,XY female condition in 63 cases (31.19%), out of which 34.57% were detected to be associated with primary, and 17.5% with SA. Included in the structural chromosomal anomaly were: 46,X,i(Xq); reciprocal translocation [46,XX,t(9;14)]; Robertsonian translocation (13;14); X; autosomal translocations (X;12 and X;14); deletion/duplication/ fragment/isochromosome/marker/ring formation associated either with the long or the short arms of X chromosome; 46,XX,9q-; 46,XX/46,XX,3p(break); in a pure free status or mostly in mosaic status. CONCLUSION: The present study has emphasized that karyotyping is one of the fundamental investigations in the evaluation of amenorrhea. It has highlighted CA, one of the genetic etiology as the causal factor in amenorrhea. PMID- 17268695 TI - Angiotensin converting enzyme inhibitors impair recombinant human erythropoietin induced erythropoiesis in patients with chronic renal failure. AB - OBJECTIVE: To investigate the effects of angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) and other anti-hypertensive agents on recombinant human erythropoietin (rHuEPO) in chronic renal failure (CRF) patients. METHODS: The present study was conducted at the Nephrology Department, Khan Research Laboratories Hospital and Quaid-i-Azam University, Islamabad, Pakistan during March 2004 to February 2005. One hundred patients, 55 males and 45 females (age range 13-78 years) were divided into 2 groups. Group-I patients received rHuEPO and ACE inhibitors/ARBs while Group-II patients received rHuEPO with other antihypertensives such as calcium channel blockers or beta adrenergic receptor blockers. Monthly increment in hematocrit (HCT%) was monitored in both groups for 4 continuous months. One-way ANOVA on Dunn's, univariate and multivariate analyses were carried out to determine any significant improvement in erythropoiesis between the 2 treatment groups. RESULTS: Monthly increase in HCT% was significantly greater in the group that was treated with rHuEPO and antihypertensives other than ACE inhibitors/ARBs compared with that treated with ACE inhibitors/ARBs, an effect observed even at a higher dose of rHuEPO, and the patients were iron replete. CONCLUSION: The present data from our population confirms that ACE inhibitors/ARBs interfere with rHuEPO therapy for treatment of anemia in CRF. The ACE inhibitors/ARBs inhibit erythropoiesis induced by rHuEPO in CRF patients, therefore, simultaneous use of ACE inhibitors/ARBs and rHuEPO should be carried out with caution. PMID- 17268696 TI - Amelioration of aluminium-induced liver damage by vitamin E. AB - OBJECTIVE: To investigate the effects of aluminium sulphate on the microscopic morphology of the liver and on vitamin E amelioration of aluminium-induced liver damage. METHODS: Rats were injected intraperitoneally with aluminium sulphate alone or aluminium sulphate together with vitamin E, with saline injected rats used as the control group. The study took place in Pamukkale University Faculty of Medicine in 2005. RESULTS: The rats exposed to aluminium showed morphological changes in addition to previously reported biochemical changes in the liver. The anti-oxidant vitamin E significantly diminished the liver damage seen due to aluminium. CONCLUSION: There is an apparent protective effect of vitamin E on parenteral aluminium exposure. PMID- 17268697 TI - Can saline be an alternative to aesthetic surgery in extended breast quadrantectomy? AB - OBJECTIVE: To explore other simpler options sparing the patients the morbidity and cost in extended breast quadrantectomy. METHODS: This prospective study was undertaken at King Fahd Hospital of the University, Al-Khobar, Eastern Province of Saudi Arabia between 1999-2005. Factors considered for patients undergoing breast-conserving surgery were based on age, tumor size, pathological characteristics, and patient's preference. Frozen section was adopted in all procedures to insure negative margins. After extended quadrantectomy, 200-400 cc was injected into the cavity to retain breast contour. Magnetic resonance imaging was used for postoperative assessment. RESULTS: Twenty-four patients were included, aged 28-43 years and tumor size 3-5 cms. All margins were negative on frozen section. The contour of the breast was restored with saline, MRI was employed for follow up at the immediate post operative period and at 4-6 months, it demonstrated restored breast contour and the saline filled cavity replaced by lipo-fibrous tissue. Follow up after 4-24 months showed that all patients noticed some degree of asymmetry, yet were satisfied with the result, none required or requested additional surgery. CONCLUSION: In large tissue excisions injecting saline into cavities temporarily prevents the caving in of the redundant skin, which has the tendency to permanently adhere to the fascia thereby preventing gross deformities. It has proven effective, contour storing and scored high satisfaction among patients. It certainly does not replace cosmetic breast surgery, however, it should be considered in centers were onco-plastic surgery is not readily available. PMID- 17268698 TI - Creation of permanent hemodialysis vascular access in patients with failed arteriovenous fistula. AB - OBJECTIVE: To compare the patency rate and complications of arteriovenous fistula (AVF) with synthetic graft in patients with previous history of failed AVF. METHODS: This study was carried out at Sina Hospital, Tehran, Iran from April 2002 to July 2003. Patients who had been referred to our center with previous failed attempt for creation of AVF were collected. We again tried to create an AVF in some of these patients according to physical examination and clinical judgment of the vascular surgeon. A synthetic graft was inserted for the remainder of the patients. All patients were followed up for 3 months. RESULTS: Elbow fistula placement was possible in 43% of patients including half of patients with diabetes and half of those more than 65 years old. Failure occurred in 33% of grafts versus 19% of fistulas. The complications were venous hypertension in one case and infection in 2 cases, all from the graft group. CONCLUSION: Our results show lower failure, mortality, and complication in AVFs than the synthetic graft, similar to previous reports. However, there were some limitations such as small sample of patients and short duration of follow up in our study. We suggest that AVF is an option even in patients who had previous multiple procedures with the advantage of being cost-effective, and with fewer complications. However, we cannot conclude any superiority for one method, as it is not a properly designed comparative trial. PMID- 17268699 TI - Detection of micrometastatic tumor cells in head and neck squamous cell carcinoma. A possible predictor of recurrences? AB - OBJECTIVE: To evaluate the presence of micrometastatic tumor cells in the peripheral blood samples of the patients with head and neck squamous cell carcinoma (HNSCC) and to determine whether the presence of micrometastatic cells had any biological relevance in terms of local recurrences or metastasis during a follow-up period of 3 years. METHODS: We included 21 consecutive patients with untreated primary HNSCC admitted to the Ear Nose and Throat Department of Akdeniz University Medical School, Antalya, Turkey between February and October 2002. Squamous carcinoma cells in peripheral blood samples of these patients prior to surgery were detected via a magnetic cell separation technique using anti epithelial cell adhesion molecule antibody, and thereafter evaluated by light microscopy with hematoxylin and eosin staining. RESULTS: Seven out of 21 patients showed squamous carcinoma cells in peripheral blood samples. Patients with stage III and IV tumors were nearly 5 times more likely to show micrometastatic cells compared with those with stage I and II tumors (6/12 versus 1/9). During the follow-up, 2 patients out of 7 with micrometastasis had recurrences. None in the micrometastasis negative group relapsed. CONCLUSION: We suggest that HNSCC patients with detectable tumor cells in peripheral blood represent a subset of patients who should be followed up more closely for possible recurrences. PMID- 17268700 TI - Enhanced susceptibility of low-density lipoprotein to oxidation in wet type age related macular degeneration in male patients. AB - OBJECTIVE: To determine the susceptibility of low-density lipoprotein (LDL) to oxidation in the plasma of male patients with wet type age related macular degeneration (AMD) and in a similar control group, in order to evaluate the LDL oxidative status as risk factor of AMD. METHODS: We conducted this study in the Retina Service, Department of Ophthalmology, Nikookari Eye Hospital-Drug of Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran during the period between October 2004 and December 2005. Sixty male patients with AMD (mean age 67 +/- 16 years) with BMI 4.1 +/- 1.3 were selected as the patient group. The control group consisted of 60 males, apparently healthy, and without ophthalmologic signs and family history of AMD. Low-density lipoprotein was isolated by gradient ultracentrifugation and susceptibility of LDL to in vitro copper-mediated oxidation was assayed by measuring conjugated dienes production (lag phase duration) at 234 nm. Lipid and lipoproteins were determined by standard methods. RESULTS: Comparing with control, significant reduction in the duration of lag phase (p<0.004) and a significant increase in LDL-C concentrations (p=0.006), were noticed. No significant change in cholesterol (p>0.3), triglyceride (p>0.1) and high density lipoprotein cholesterol (p>0.1) levels were found between control and patient groups. A significant negative correlation between Lag phase and LDL-C levels (p=0.004, r=-0.364) was found in the patient group. CONCLUSION: The increased LDL concentration and enhanced susceptibility of LDL to oxidation may play a roll in the wet type AMD process. PMID- 17268701 TI - Treatment of Graves' hyperthyroidism--prognostic factors for outcome. AB - OBJECTIVE: To determine whether clinical and biochemical features of Graves' disease at presentation predict response to medical and radioiodine treatment. METHODS: We carried out a retrospective 10-year study of 194 consecutive Saudi subjects with Graves' disease who were treated with antithyroid drugs, radioiodine therapy, or both, between January 1995 and December 2004 at King Khalid University Hospital, Riyadh, Saudi Arabia. RESULTS: At diagnosis, the mean age was 32 +/- 0.9 years. Only 26% of patients had successful outcome after a course of antithyroid medication. None of the clinical or biochemical factors were associated with a favorable outcome of antithyroid treatment. One dose of radioiodine [13-15 mCi (481-555 MBq)] cured hyperthyroidism in 83% of patients. Presence of ophthalmopathy at presentation was shown to be a significant contributing factor to failure to respond to a single dose of radioiodine (odds ratio, 6.4; 95% CI, 1.51-24.4; p<0.01). Failure of radioiodine treatment was also associated with higher serum free T3 concentration at presentation (p=0.003). CONCLUSION: In patients with Graves' hyperthyroidism, radioiodine treatment is associated with higher success rate than antithyroid drugs. A dose of 13-15 mCi (481-555 MBq) seems to be practical and effective, and should be considered as first line therapy. Patients with high free T3 concentration and, those with ophthalmopathy at presentation were more likely to fail radioiodine treatment. A higher dose of radioiodine may be advisable in such patients. PMID- 17268702 TI - Bacterial isolates from fatal cases of bloodstream infections at a university hospital in Central, Saudi Arabia. AB - OBJECTIVE: To describe the microbiology, underlying medical conditions and risk factors contributing to bloodstream infection (BSI) and mortality at a University Hospital in Riyadh, Kingdom of Saudi Arabia. METHODS: We conducted this study at King Khalid University Hospital, Riyadh, Saudi Arabia, wherein clinical data from patients who died with BSI were collected. All isolates from these patients, from 1 January to 31 December 2004, were identified and antimicrobial susceptibilities were determined. RESULTS: Of the total 778 patients with BSI, 82 (10.5%) died. Among which 34 (41.5%) were elderly. Half of the patients were from the intensive care units (ICUs). Cardiovascular diseases were the most common diagnosis in 14 (17.1%) patient, followed by malignancy 13 (15.9%), and respiratory diseases 12 (14.6%). Eleven (13.4%) had chronic liver diseases, 6 (7.3%) with renal diseases, sepsis in 5 (6.1%), 4 (4.8%) were post- surgical cases, 3 (3.7%) cases had systemic lupus erythematosus (SLE) and 3 premature infants. The majority of BSI episodes were monobacterial, 71(86.5%). Over 90% of the isolates were hospital acquired. Coagulase negative Staphylococci (CoNS) were the most common organisms representing 25 (30.5%) of all organisms isolated, while Gram positive as a whole represented 50 (61%). Thirty one (38%) were Gram negative bacteria among which Pseudomonas species 6 (7.3%) and Escherichia coli (E. coli) 5 (6%) were the most common. Two (2.4%) of isolates were Candida glabrata. CONCLUSION: Mortality in our patients with BSI was attributed to old age and underlying medical conditions. The risk factors for nosocomial BSI were ICU admission, intravascular catheterization and respiratory tract infections. PMID- 17268703 TI - Trends in emergency department utilization in a hospital in the Eastern region of Saudi Arabia. AB - OBJECTIVE: To examine the changes in emergency department (ED) utilization over a 3-year period and identify the factors that affect utilization. METHODS: We performed an analysis of administrative ED records at King Abdul-Aziz Hospital from the years 2003 to 2005 for all patients to assess the demographic characteristics, periodicity of ED use, and acuity level. RESULTS: During the study period, the number of ED visits increased approximately 30%. Patients demographic characteristics, periodicity, and acuity were comparable for ED visits across each study year. Fall (between September and November) was the busiest season (30%), and the greatest volume was between 3 and 11 pm (57.5% of all visits). We found that 52% had 1 visit, 18% had 2 visits, 12% had 3 visits, and 8% had 4 or more visits. The Canadian Triage and Acuity Scale (CTAS) IV and V visits comprised 59.5% of the ED visits. The patients' admission has increased from 7.2-9%, while the ED length of stay increased from 72 minutes to 78 minutes during the study period. CONCLUSION: Emergency department utilization increased during the study period, with almost no change in the proportions for triage category. The numbers of patients requiring hospital admission increased, as the length of their stay. Nearly 60% of emergency visits are for CTAS IV and V care. There were significant patients with multiple visits to ED. We recommend the strengthening of the primary health care in our institution and a designated "Fast Track" in ED for the expeditious management of low acuity patients. PMID- 17268704 TI - Child abuse and neglect in the Arab Peninsula. AB - OBJECTIVE: To provide an overview of the problem and patterns of child abuse and neglect in the 7 countries of the Arab Peninsula, and to highlight some of the difficulties and shortcomings. METHODS: This study was conducted by reviewing medical literature, published between January 1987 and May 2005. In addition, reports were obtained from regional meetings and professional organizations. Each study or report was reviewed, assessed, and summarized. RESULTS: Three studies from Kuwait identified 27 children; 22 with physical abuse, 3 with sexual abuse, and 2 with Munchausen's syndrome by proxy (MSP), and 3 deaths. Eleven case reports from Saudi Arabia identified 40 abused children; 24 with physical abuse, 6 with sexual abuse, 4 with MSP, and 6 with neglect. Fatal outcome was documented in 5 children. In Oman, 5 cases of MSP were reported. A total of 150 hospital based cases were reported from Bahrain; 50 with physical abuse, 87 with sexual abuse, and 10 with both forms of abuse. In Yemen, population based surveys revealed a wide spread use of corporal punishments and cruelty to children at homes, schools, and juvenile centers, which ranged from 51-81%. CONCLUSION: Children in the Arab Peninsula are subjected to all forms of child abuse and neglect. Child abuse is ignored or may even be tolerated and accepted as a form of discipline, abused children continue to suffer and most abusers go free, unpunished and untreated. Confronting these realities is a necessary step in the long and hard road to break silence, respond to and prevent child abuse and neglect in the Arab Peninsula. PMID- 17268705 TI - Prevalence and severity of anemia in pediatric hemodialysis patients. AB - OBJECTIVE: To determine the prevalence and severity of anemia, and to identify independent predictors for anemia in children on hemodialysis. METHODS: We conducted this cross sectional study on 25 children aged 7-20 years receiving hemodialysis from September 2005 to January 2006 in Isfahan University of Medical Sciences, Isfahan, Iran. RESULTS: A total of 22 (82%) patients had hemoglobin (Hb) level of <11 g/dL (anemia) and 12 (48%) patients had Hb values <8 g/dL (severe anemia). The mean age was 15.5 +/- 3.7 years. Mean time on hemodialysis was 20.44 +/- 15.25 months. Anemia was more common and severe among children who were on dialysis <6 months. There was an inverse relation between severity of anemia and duration of hemodialysis (r=-0.465, p=0.019). Nearly all patients were treated with recombinant human erythropoietin (rHuEPO). Children with severe anemia received a slightly higher dose of erythropoietin (r=0.202 p=0.09). There was a correlation between serum albumin and Hb level (r=0.511, p=0.01). Intact parathyroid hormone (iPTH) levels were >200 pg/mL in 16 patients (66%) and >400 pg/mL in 9 patients (37.5%). There was a reverse correlation between iPTH level >200 pg/mL and Hb level (r=-0.505, p=0.046). CONCLUSION: The prevalence of anemia in our study appears to be higher than that reported in the other studies in spite of extensive use of rHuEPO and iron supplementation. We found this to be especially true for patients who were on dialysis <6 months and with low albumin and severe hyperparathyroidism. PMID- 17268706 TI - Passive or active smoking, which is more relevant to breast cancer. AB - OBJECTIVE: To examine the risk of breast cancer associated with passive and active smoking and to explore risk heterogeneity among studies. METHODS: We conducted this study in Iran during the year 2006. Fifteen published studies on smoking and breast cancer met the defined criteria. Pooled odds ratio (OR) estimates for female breast cancer were calculated. The active and passive smokers were compared with women categorized as never regularly exposed to tobacco smoke. RESULTS: The pooled risk estimate for breast cancer associated with passive smoking among non-smokers was 1.38 (95% confidence interval [CI]; 1.16-1.65). The pooled OR for active smokers was 1.25 (95% CI; 1.11-1.41). Also, the combined OR for passive and active smokers related to breast cancer was 1.30 (95% CI; 1.17-1.45). CONCLUSION: Based on the results of the pooled analysis, it can be concluded both passive and active smoking equally increase the risk of female breast cancer. PMID- 17268707 TI - Fatal congenital cytomegalovirus infection following recurrent maternal infection after a 7-year interval. AB - It is generally accepted that the risk for fetal infection is greatest with maternal primary cytomegalovirus CMV infection and much less likely with recurrent infection. Here, we report a fatal case of congenital CMV infection following recurrent maternal infection after a 7-year interval. A 3-month-old female baby presented with fever, jaundice, vomiting and stopping breast-feeding. Physical examination revealed mild respiratory distress, hepatosplenomegaly, microcephaly and growth retardation. Laboratory examination included bilirubin concentrations Total: 7.17 mg/dl; conjugated 6.67 mg/dl, aspartate transaminase 141 IU, and alanine transaminase 499 IU. Enzyme-linked immunosorbent assay test results revealed + CMV IgM and + CMV IgG. She died on the 10th day of admission with the diagnosis of CMV hepatitis, pneumonia, and multi-organ failure. Nuclear and cytoplasmic inclusions were demonstrated in the lung, liver and brain on postmortem biopsy. This case highlights that the outcome of babies born to mothers with recurrent maternal CMV infection may be more severe and fatal than previously thought. PMID- 17268708 TI - Usefulness of molecular techniques to identify ongoing tuberculosis transmission in Saudi Arabia. AB - This study represents the first time that molecular tracing techniques have been used to identify patterns of tuberculosis TB infection in Saudi Arabia. The 2 strains were isolated from a socio-economically advantage family who share a number of common facilities including a car and a driver. There are several factors that may play vital roles in on-going transmission of TB in Saudi Arabia including a high number of expatriates, the Hajj pilgrimage, and the social habits of Saudi citizens. Our sibling case series is believed to be a frequent pattern of disease transmission in this country. Control measures such as health education, active case finding, and prompt and supervised medical treatment are needed. More studies using molecular techniques are recommended to find the incidence of cross infection in Saudi Arabia. In addition, molecular techniques have to be established in all reference laboratories to help the detection of ongoing active transmission, molecular epidemiology and detect sources of infection. PMID- 17268709 TI - Infarction of spleen in typhoid fever. AB - Ultrasonography and computed tomography scan with hypo echoic areas diagnosed a splenic infarction in a Salmonella typhi infected 30-year-old man with painful hypochondrium and epigastrium. An antibiotic recipe of ceftriaxone and amikacin resulted in recovery. Imaging techniques contribute remarkably to a rapid diagnosis and rational management of the extra intestinal lesions attributable to the Salmonella typhi/paratyphi group of organisms. PMID- 17268710 TI - An unusual presentation of postpartum ovarian vein thrombosis. AB - Ovarian vein thrombosis is a rare but potentially serious complication following childbirth. The majority of patients present during the first week postpartum, with fever and right lower quadrant abdominal pain. We report an unusual case of postpartum ovarian vein thrombosis who presented with fever, low backache, and painful thighs. A high index of suspicion is crucial to diagnose and treat this condition in order to avoid serious consequences. PMID- 17268711 TI - Mesenteric panniculitis. Imaging of a rare cause of chronic abdominal pain. AB - We report a case of mesenteric panniculitis. This rare and poorly-known disease is characterized by a nonspecific inflammatory process involving the adipose tissue of the mesentery. This case illustrates its computerized tomographic and magnetic resonance imaging features and the value of imaging in differentiating it from other mesenteric diseases and thus, avoiding unnecessary surgery. PMID- 17268712 TI - Currarino triad associated with malrotation of the colon. AB - Currarino triad is a rare congenital condition characterized by a sacral bony defect, presacral mass, and anorectal malformations. We describe an unusual case of complete Currarino triad in a 22-year-old female with sacral bony defect, anal stenosis, recto-vaginal fistula, and dual pathology meningocele and teratoma in the pre sacral mass associated with malrotation of the colon. This combination has not been reported previously. The clinical presentation, surgical management and review of literature are discussed. PMID- 17268713 TI - Neurogenic stunned myocardium following hemorrhagic cerebral contusion. AB - Neurogenic stunned myocardium NSM is a well-known complication of subarachnoidal hemorrhage, but has been reported rarely in association with other central nervous system disorders. A case of NSM is described in a patient with hemorrhagic brain contusion associated with cerebral edema. An 18-year-old man was admitted with severe cranial trauma following a car roll-over. Six days after admission, he developed findings suggestive for NSM. The troponin T and creatine kinase-MB level were elevated and echocardiogram showed apical and inferoposterior hypokinesis and diffuse left ventricular akinesis with severely reduced ejection fraction 18%. Invasive measurements confirmed low cardiac output. His cardiac function resolved completely within 6 days after decompressive craniotomy. This case supports the presumed unifying role of the increased intracranial pressure, probably triggering a vigorous sympathetic outflow hyperactivity leading to NSM. PMID- 17268714 TI - Late pulmonary metastasis of renal cell carcinoma after nephrectomy. PMID- 17268715 TI - The effect of melatonin on ductus epididymis. Unilateral testicular torsion in rats. PMID- 17268716 TI - Free radical and antioxidant enzyme levels at exposure of volatile organic compounds in workers. PMID- 17268717 TI - Synchronous occurrence of Philadelphia chromosome-positive chronic myelogenous leukemia and breast cancer. PMID- 17268718 TI - Prevalence of risk factors of coronary heart disease among diabetic patients in Medina city. PMID- 17268719 TI - Light and scanning electron microscopic investigation of the changes in hair with Dyskeratosis congenita. PMID- 17268720 TI - Fundamental rights of infants are guaranteed in Islam--breastfeeding is mandatory. PMID- 17268721 TI - Protozoa infection and its associated factors among urban babies 6 to 24 months age, in Semnan, Iran. PMID- 17268722 TI - An unique and unusual lucent shadow seen on a plain x-ray abdomen anteroposterior view in erect position. PMID- 17268723 TI - Primary hyperparathyroidism due to parathyroid adenoma. PMID- 17268724 TI - Etiology of community-acquired pneumonia in hospitalized patients in Jordan. PMID- 17268725 TI - Compliance with maintenance treatment of asthma (ADERE study). AB - OBJECTIVE: To determine the rate of compliance with preventive treatment of moderate and severe persistent asthma. METHODS: Physicians at various medical centers across the country were invited to nominate patients for participation in the study. Inclusion criteria were being over the age of 12 and presenting moderate or severe persistent asthma. Participating patients received salmeterol/fluticasone 50/250 microg by dry powder inhaler for 90 days and were instructed to return the empty packages at the end of the study as a means of determining the total quantity used. In order to evaluate compliance, a member of the research team contacted each patient via telephone at the study outset and again at the end of the 90-day study period. Asthma patients were considered compliant with the treatment if they used at least 85% of the prescribed dose. The following variables were studied: gender, age, race, marital status, years of schooling, smoking habits, other atopic conditions, comorbidities, asthma severity, use of other medication and number of hospital admissions for asthma. RESULTS: A total of 131 patients from fifteen states were included. The overall rate of compliance was found to be 51.9%. There was a significant difference in compliance in relation to asthma severity: compliance was greater among patients with severe persistent asthma than among those with moderate persistent asthma (p = 0.02). There were no statistically significant differences among any of the other variables. CONCLUSION: The overall rate of compliance with maintenance treatment of asthma was low. PMID- 17268726 TI - Seasonal variations in emergency room visits for asthma attacks in Gama, Brazil. AB - OBJECTIVE: To quantify the number of asthma attacks treated in the emergency room of a public hospital and to study seasonal fluctuations, taking into consideration the local climate, which is characterized by having only two seasons: a rainy/humid season and a dry season. METHODS: A retrospective survey was conducted in a community general hospital. A total of 37,642 emergency room consultations related to asthma, bronchitis, pneumonia, upper-airway infection or other respiratory complaints were registered during a two year period. The data from each patient chart were collected for later analysis. RESULTS: Among the respiratory conditions treated, asthma (24.4%) was the second most common diagnosis. Most of the asthma consultations (56.6%) involved children below the age of fifteen. Regression analysis revealed a seasonal variation in the number of asthma consultations, which was significantly higher in March (p = 0.0109), the low points being in August (p = 0.0485) and September (p = 0.0169). The correlation between climate and asthma was most significant in relation to changes in humidity, although the effect was delayed by one month (p = 0.0026) or two months (p = 0.0002). CONCLUSION: Visits to the emergency room for the treatment of asthma attacks were more frequent during the rainy season, increasing at one to two months after the annual increase in humidity and decreasing in the dry season. This positive correlation raises the possibility of a causal relationship with proliferation of house dust mites and molds. PMID- 17268727 TI - Post-pneumonectomy thoracic drainage: to drain or not to drain? A retrospective study. AB - OBJECTIVE: To evaluate the need for post-pneumonectomy thoracic drainage. METHODS: This was a retrospective study of 46 patients having undergone pneumonectomy in the Thoracic Surgery Department of the Londrina University Hospital between January of 1998 and December of 2004. Patients were divided into two groups: those having been submitted to drainage and those not having been. The diseases involved were lung cancer, bronchiectasis and tuberculosis. RESULTS: Drainage was used in 21 patients, whereas no drainage was used in 25. The most common postoperative complication was subcutaneous emphysema (12 cases). Hospital stays were of shorter duration among patients who were not submitted to drainage than among those who were (mean, 6.5 days vs. 10.2 days). No serious postoperative complications were observed in the group of patients not submitted to drainage. CONCLUSION: The findings that evolutions were more favorable and hospital stays were shorter for the patients not submitted to drainage call into question the need for routine post-pneumonectomy drainage. PMID- 17268728 TI - The relative frequency of hypomagnesemia in outpatients with chronic airflow limitation treated at a referral center in the north of the state of Parana, Brazil. AB - OBJECTIVE: To determine the relative frequency of hypomagnesemia among patients with chronic airflow limitation treated as outpatients at a referral center in the northern part of the state of Parana between 2000 and 2001, as well as to determine whether hypomagnesemia correlates with hypoxia, with other electrolyte disturbances and with the severity of airflow limitation. METHODS: This was a descriptive study of the relative frequency of hypomagnesemia in 72 patients with chronic airflow limitation. All of the patients were submitted to blood tests to determine serum levels of magnesium and other electrolytes, as well as to staging of the underlying disease. RESULTS: The prevalence of hypomagnesemia was 27.8%. The mean age was 65 +/- 9.9 years, and there was a predominance of males. The mean forced expiratory volume in one second was 1.31 +/- 0.52 L. Most of the patients (68.1%) were found to be in the advanced stages of the disease. Hypomagnesemia was not found to correlate with other electrolyte disturbances, hypoxemia or disease stage. CONCLUSION: The high frequency of patients in the advanced stages is likely attributable to the fact that the outpatient facility is a referral center for the region. Further studies should be conducted in order to determine the probable causes of this high prevalence of hypomagnesemia. PMID- 17268729 TI - Potential consequences for stable chronic obstructive pulmonary disease patients who do not get the recommended minimum daily amount of physical activity. AB - OBJECTIVE: The present study attempted to determine whether patients with chronic obstructive pulmonary disease (COPD) get the minimum daily amount of physical activity recommended in the guidelines established by the American College of Sports Medicine (ACSM), as well as to characterize the consequences of noncompliance with those guidelines. METHODS: This study involved 23 patients (median age: 61--range, 59-69 years; FEV1: 39% of predicted--range, 34-53%; BMI: 24 kg/m(2)--range, 21-27 kg/m(2)). The following parameters were evaluated: daily physical activity (DynaPort activity monitor); pulmonary function; muscle force; exercise tolerance; quality of life; functional status; and various indices of disease severity (GOLD, BODE and MRC). RESULTS: Based on compliance with the guidelines (minimum of 30 minutes of walking per day), 12 patients were considered "physically active", and 11 were considered "physically inactive". No significant differences were observed between the two groups in terms of age, gender, BMI, muscle force, ventilatory reserve, hyperinflation or quality of life. The inactive group presented more impaired pulmonary function and lower exercise tolerance, as well as lower MRC and BODE scores (p < 0.05). In their daily life, patients in the inactive group also walked for less time and more slowly than did those in the active group (p < 0.05). The MRC and BODE indices were superior to the GOLD index in predicting compliance with the guidelines, both presenting a specificity of 0.83, compared with 0.50 for the GOLD index. The BODE index score increased significantly with each day of inactivity. CONCLUSION: A large number of COPD patients do not walk more than 30 minutes per day and are therefore not getting the minimum daily amount of physical activity recommended by the ACSM. Inactivity correlates with a higher mortality rate. The MRC and BODE indices proved superior to the GOLD index in predicting whether patients are physically inactive in their daily lives. PMID- 17268730 TI - Profile of research published in the annals of the Brazilian Pulmonology and Phthisiology Conferences held over the last twenty years. AB - OBJECTIVE: To increase the knowledge base regarding pulmonology research in Brazil. METHODS: A retrospective, observational study of the abstracts published in the Annals of the Brazilian Pulmonology and Phthisiology Conferences held from 1986 to 2004, quantifying the institutions of origin by geographic distribution and type, as well as categorizing the abstracts by study design and topic. RESULTS: A total of 6467 abstracts were published. The institutions of origin were located, variously, in the Southeast (3870 abstracts), South (1309), Northeast (783), Central-West (267) and North (84). There were 94 abstracts originating from foreign institutions, especially from institutions in Portugal (56.3%) and the United States (13.8%). Most of the studies (5825) were conducted in public Brazilian institutions. There were 4234 clinical studies, 1994 case reports and 239 original research articles. A marked, progressive increase was observed in the number of clinical studies and case reports during the period evaluated. Overall, the most common themes were tuberculosis and other infections diseases (25.2%), following by oncology (11.6%), interstitial lung diseases (8.8%) and thoracic surgery (8.5%). Nevertheless, the number of abstracts on each topic varied widely from year to year. CONCLUSION: Public Brazilian institutions are the principal sources of pulmonology research in Brazil. Such research activity is concentrated in the southeastern part of the country. Case reports account for one-third of this activity. Although there was great variability in the subjects addressed, diseases that are highly prevalent in Brazil, such as tuberculosis and other infections diseases, were the most common topics. PMID- 17268731 TI - Analysis of pulmonary mechanics in an experimental model of sepsis. AB - OBJECTIVE: To determine whether pulmonary mechanics are altered in mice with sepsis. METHODS: A total of 40 Balb/c mice were divided into two groups: survival (n = 21) and pulmonary mechanics (n = 19). The survival group was divided into three subgroups: control (n = 7), sublethal (n = 7) and lethal (n = 7). The pulmonary mechanics group was also divided into three subgroups: control (n = 5), sublethal (n = 7) and lethal (n = 7). Sepsis was induced through cecal ligation and puncture, the latter varying in degree (sublethal or lethal). At eight hours after the intervention, pulmonary mechanics were measured through end-inflation occlusion. In the pulmonary mechanics group, the following variables were studied: total pressure, resistance, viscoelasticity, dynamic compliance and static compliance. The data obtained were analyzed using one-way ANOVA. RESULTS: The data for the survival group indicate the efficacy of the model employed. There were no statistically significant differences among the pulmonary mechanics subgroups in terms of dynamic compliance, static compliance, total pressure, resistance or viscoelasticity. CONCLUSION: At eight hours after cecal ligation and puncture, there were no changes in the lung parenchyma, nor were any alterations observed in the viscous and viscoelastic components of the lung. PMID- 17268732 TI - Morphological aspects as prognostic factors in malignant mesothelioma: a study of 58 cases. AB - OBJECTIVE: Various markers have shown promise as diagnostic markers and prognostic predictors in malignant mesothelioma (MM). METHODS: Through morphometric and immunological studies of markers in stromal components (calretinin, CEA, Leu-M1 and thrombomodulin) and nuclear components (p53 and Ki 67), we evaluated post-diagnosis survival in 58 patients with MM. RESULTS: The histologic pattern of the MM was typical in 50 cases and atypical in 8. Through immunohistochemistry, we confirmed 40 cases of mesothelioma and 11 cases of adenocarcinoma, although we were unable to classify 7 of the 8 cases presenting atypical histologic patterns. Cox multivariate analysis revealed that the risk factor for death was higher (476.2) among patients of advanced age, presenting the biphasic subtype and testing positive for components expressed at the nuclear level. CONCLUSION: The most useful immunohistochemical markers were was calretinin (for mesothelioma) and CEA (for adenocarcinoma). Immunohistochemical quantification of thrombomodulin facilitated the diagnosis of mesothelioma in patients testing positive for both calretinin and CEA. The most useful prognostic information was that provided by the routine histopathological analysis of the tumor type. It is of note that the combination of a mean age of 55 years and 30.5% immunohistochemical markers in nuclear components created a natural dividing point between patients in which survival was shorter than expected and those in which it was longer than expected. Therefore, histopathological analysis offers a powerful weapon with great potential to inform decisions regarding the use of adjuvant chemotherapy after surgical excision of a mesothelioma. PMID- 17268733 TI - Sleep disordered breathing concomitant with fibromyalgia syndrome. AB - OBJECTIVE: To identify fibromyalgia syndrome in patients with sleep disordered breathing. METHOD: We studied 50 patients seeking treatment at a sleep disorder clinic for snoring, apnea and excessive daytime sleepiness. Sleep disordered breathing was diagnosed through the use of polysomnography. To diagnose fibromyalgia syndrome, patients were evaluated in accordance with the criteria established by the American College of Rheumatology. RESULTS: Of the 50 patients, 32 were male. The mean (+/- standard deviation) age of the group was 50 +/- 12 years. The mean body mass index was 29.7 +/- 5.6 kg/m(2). The mean apnea-hypopnea index was 36 +/- 29 attacks of apnea or hypopnea per hour of sleep. Of the 18 women and 32 men evaluated, 9 and 2, respectively, met the American College of Rheumatology criteria for fibromyalgia syndrome. CONCLUSION: Considering the fact that the prevalence of fibromyalgia syndrome in the general population is 0.5% for men and 3.4% for women, the more than ten-fold higher proportion of fibromyalgia cases seen in this sample supports the hypothesis that there is an association between sleep disordered breathing and fibromyalgia syndrome. PMID- 17268734 TI - Prevalence of ventilator-associated pneumonia in a university hospital and prognosis for the patients affected. AB - OBJECTIVE: To determine the prevalence of ventilator-associated pneumonia in an intensive care unit, as well as to identify related factors and characterize patient evolution. METHODS: This study evaluated 278 patients on mechanical ventilation for more than 24 hours in a university hospital. RESULTS: Ventilator associated pneumonia developed in 38.1% of the patients, translating to 35.7 cases/1000 ventilator-days: 45.3% were caused by gram-negative agents (Pseudomonas aeruginosa accounting for 22%); and multidrug resistant organisms were identified in 43.4%. In the ventilator-associated pneumonia group, time on mechanical ventilation, time to mechanical ventilation weaning, hospital stays and intensive care unit stays were all longer (p < 0.001). In addition, atelectasis, acute respiratory distress syndrome, pneumothorax, sinusitis, tracheobronchitis and infection with multidrug resistant organisms were more common in the ventilator-associated pneumonia group (p < 0.05). Mortality rates in the intensive care unit were comparable to those observed in the hospital infirmary. Associations between ventilator-associated pneumonia and various factors are expressed as odds ratios and 95% confidence intervals: acute sinusitis (38.8; 3.4-441); > 10 days on mechanical ventilation (7.7; 4.1-14.2); immunosuppression (4.3; 1.3-14.3); acute respiratory distress syndrome (3.5; 1.4 9.0); atelectasis (3.0; 1.2-7.3); cardiac arrest (0.18; 0.05-0.66); and upper gastrointestinal tract bleeding (0.07; 0.009-0.62). The variables found to be associated with in-hospital death were as follows: chronic renal failure (26.1; 1.9-350.7); previous intensive care unit admission (15.6; 1.6-152.0); simplified acute physiologic score II > 50 (11.9; 3.4-42.0); and age > 55 years (4.4; 1.6 12.3). CONCLUSION: Ventilator-associated pneumonia increased the time on mechanical ventilation and the number of complications, as well as the length of intensive care unit and hospital stays, but did not affect mortality rates. PMID- 17268735 TI - Pleurodesis: technique and indications. AB - Recurrent pleural effusion, which is commonly seen in clinical practice, compromises patient quality of life, especially in patients with advanced malignant disease. The therapeutic approach to the pleural space involves a wide range of techniques, including aggressive procedures such as pleurectomy. Among such techniques, pleurodesis is the most frequently used. Pleurodesis can be induced through the insertion of pleural catheters, as well as through major surgical procedures (such as thoracotomy). There are various recommended sclerosing agents, including talc (which is the most widely used), silver nitrate and, recently, proliferative cytokines. This article summarizes the principal approaches to the treatment of recurrent pleural effusion, pleurodesis in particular, addressing the indications for, as well as the advantages and disadvantages of, their application in daily pulmonology practice. PMID- 17268736 TI - Rhinitis, sinusitis and asthma: hard to dissociate? AB - The objective of this study was to review the literature and to discuss epidemiological and physiopathological aspects and therapeutical implications of an unified approach to allergic rhinosinusitis and asthma. The bibliographic survey was based on the information provided by the following databases: Medline, MD Consult, Highwire, Medscape, LILACS and through direct search over thirty years, using the terms allergic rhinitis and asthma. Fifty-five original articles were selected in the no systematically review addressing the issue of clinical association between allergic rhinusinusitis and asthma. It is noteworthy that in the late years, with the use of specific topical medications for the lower airways or else, to the upper airways, the therapeutical approach has been distinct. However, numerous epidemiological surveys, immunopatological and clinical studies demonstrate the inter-relationship between asthma and allergic rhinossinusitis, characterized by: i) allergic rhinitis is associated to asthma and constitute an independent risk factor for its occurrence; ii) the immunopathological characteristics of allergic rhinitis and asthma are similar; iii) allergic rhinitis and asthma are manifestations of a systemic disease; iv) control of rhinitis favors asthma control. taking into consideration the close inter-relationship between allergic rhinitis and asthma, the approach to diagnosis, treatment and prophylaxis of these illnesses should be integrated. Therapeutical options that allow for the simultaneous control of asthma and allergic rhinitis offer advantages related both to costs and tolerability. PMID- 17268737 TI - Asthma and Churg-Strauss syndrome. AB - We report the case of a 25-year-old woman with Churg-Strauss syndrome, the symptoms of which had first appeared soon after she began taking oral contraceptive at the age of sixteen. The clinical profile evolved rapidly to severe persistent asthma, nasal polyposis, perennial obstructive rhinitis, eosinophilia (peripheral/tissue) and mononeuritis. Churg-Strauss syndrome is the type of disease that demands early detection, accurate diagnosis, aggressive treatment and periodic monitoring. It should be considered in the differential diagnosis of moderate and severe persistent asthma. The case reported calls attention to possibility that there is a hormonal component and that the disease can present early onset. PMID- 17268738 TI - Intrathoracic goiter and invasive thymoma: rare concomitant presentation. AB - We present a rare situation in which two mediastinal tumors of different topology and histology were found during the resection of an extensive mediastinal tumor in an asymptomatic patient. Different histologies within the same mass have been reported, although, to our knowledge, there have been no reports of different tumors at distinct locations. Thymomas and intrathoracic goiters account for a large proportion of the tumors found in the mediastinum. When feasible, surgical resection plays a fundamental role in effecting a cure. In order to identify concomitant lesions and perform a complete resection, detailed surgical exploration is required. PMID- 17268739 TI - An outbreak of histoplasmosis in the city of Blumenau, Santa Catarina. AB - Acute pulmonary histoplasmosis is rarely diagnosed and is often confused with tuberculosis. Most knowledge of the disease has been derived from descriptions of epidemics in which a number of individuals were exposed to the same source of infection. Isolation of Histoplasma capsulatum var. capsulatum from soil samples is conclusive evidence of an epidemic focus. This is the first report of an outbreak of histoplasmosis, in which two cases were reported and the fungus was isolated at the focus of the epidemic, in the state of Santa Catarina. Further epidemiological studies are needed in order to determine the prevalence of the infection statewide. PMID- 17268740 TI - Asthma management in a public referral center in Porto Alegre in comparison with the guidelines established in the III Brazilian Consensus on Asthma Management. AB - OBJECTIVE: To determine whether the guidelines put forth in the III Brazilian Consensus on Asthma Management are being applied in a population of asthma patients treated at a public hospital that is a referral center for asthma in the city of Porto Alegre, Brazil. METHODS: All adult asthma patients who began their treatment between 1999 and 2002 were evaluated. The treatment given was classified as consistent or inconsistent with the Consensus guidelines. The clinical features of asthma and the frequency of treatment provided by a specialist were compared between the two groups (those receiving guideline consistent treatment and those receiving guideline-inconsistent treatment). RESULTS: The charts of 357 patients were evaluated. The study sample consisted of 106 males (29.9%) and 251 females (70.3%). The mean age was 41 years, and 33 (9.2%) of the patients were smokers. The treatment was considered inconsistent with the Consensus guidelines in 246 cases (70%). Of those 246, 174 (71%) had presented persistent asthma and were not treated with an inhaled corticosteroid. Normal forced expiratory volume in one second, being from 12 to 18 years of age, and having intermittent asthma were more frequently observed among the patients receiving guideline-consistent treatment (p < 0.01). No correlations were found between guideline-inconsistent treatment and being treated by a pulmonologist, severity of persistent asthma or number of emergency room visits. CONCLUSION: Most of the asthma patients treated at the public referral center in Porto Alegre did not receive treatment that was consistent with the Consensus guidelines. Undertreatment with inhaled corticosteroids was the principal source of that inconsistency. PMID- 17268741 TI - Risk factors for multiple hospital admissions among children and adolescents with asthma. AB - OBJECTIVE: To determine the influence that hospital admission of suckling infants with asthma has on their risk for future admissions for the same cause. METHODS: A retrospective study was conducted, in which the charts of 202 patients, all less than fifteen years of age, were evaluated. All of the patients had been treated as outpatients in a pediatric pulmonology clinic and had been admitted to the hospital on one or more occasions. A multivariate analysis was conducted in order to evaluate the risk factors associated with multiple hospitalizations. RESULTS: Virtually all of the patients evaluated were hospitalized a second time within 18 months of the first hospitalization. Among the patients first hospitalized at = 12 months of age, the second admission occurred sooner than did that recorded for those first hospitalized at > 12 months of age (p = 0.001). The risk factors found to be associated with multiple hospital admissions were as follows: age at first admission = 12 months (odds ratio: 2.55; 95% confidence interval: 1.18-5.48); age at first admission between 13 and 24 months (odds ratio: 3.54; 95% confidence interval: 1.31-9.63); and severity of asthma symptoms (odds ratio: 3.86; 95% confidence interval: 2.02-7.40). CONCLUSION: After the first hospitalization, children with asthma should be closely monitored, since the risk of subsequent admissions is elevated in the first months following discharge, especially among those of less than two years of age. Health care facilities should be organized to confront this problem appropriately and should dispense prophylactic medication more freely. PMID- 17268742 TI - Pulmonary auscultation terminology employed in Brazilian medical journals between January of 1980 and December of 2003. AB - OBJECTIVE: To evaluate the appropriateness of the use of auscultation terminology in Brazilian respiratory disease-related medical journals published between January of 1980 and December of 2003. METHODS: A descriptive study was conducted, evaluating three medical journals: the Jornal de Pneumologia (Journal of Pulmonology), Jornal de Pediatria (Journal of Pediatrics) and Revista Brasileira de Medicina (Brazilian Journal of Medicine). Original articles and case reports about respiratory diseases were selected, and auscultation terminology was extracted from these articles. The appropriateness of terms used to describe adventitious sounds was assessed. RESULTS: We found that the inappropriate use of terms was more frequent when intermittent sounds were described than when continuous sounds were described (87.7% versus 44.0%; p = 0.0000). No significant difference was observed between the inappropriate use of terms by pulmonologists and that observed for other specialists (56.5% versus 62.0%; p = 0.26). In addition, there were no significant differences among the various regions of the country or between the periods prior to and after the dissemination of international nomenclature. CONCLUSION: Inappropriate use of pulmonary auscultation terms describing adventitious sounds remains common and widespread in Brazilian medical publications. PMID- 17268743 TI - Rhodococcus equi infection in acquired immunodeficiency syndrome. Computed tomography aspects. AB - OBJECTIVE: To present the computed tomography aspects of Rhodococcus equi pneumonia in seven patients with acquired immunodeficiency syndrome. METHODS: A retrospective study of the computed tomography scans of seven patients with acquired immunodeficiency syndrome and Rhodococcus equi infection. RESULTS: The most common findings were consolidation (n = 7), consolidation with cavitation (n = 6), ground glass opacities (n = 6), peribronchial nodules (n = 4) and centrilobular nodules presenting a "tree-in-bud" pattern (n = 3). CONCLUSION: The most common finding in patients with Rhodococcus equi pulmonary infection and acquired immunodeficiency syndrome was consolidation with cavitation. PMID- 17268744 TI - Outpatient smoking cessation program in the state of Ceara, Brazil: patient profiles and factors associated with treatment success. AB - OBJECTIVE: To evaluate patient profiles and factors associated with successful treatment. METHODS: A retrospective study of patients enrolled in the smoking cessation program at the Hospital de Messejana, located in the state of Ceara, Brazil, from October of 2002 to April of 2005. The treatment was evaluated based on patient profile, type of medication prescribed and time on that medication. RESULTS: Of the 320 patients enrolled, 65.5% were women. The mean age at the outset of treatment was 48 years, and the mean duration of the smoking habit was 33 years. More than 90% of the patients had started smoking before the age of 20. Of the 258 individuals who had enrolled in the program at least one year prior, 50.8% had achieved treatment success; 17.8% had relapsed, and 31.4% had not quit smoking. On average, partial success was achieved in the fifth week of the treatment, and relapse occurred predominantly in the fourth month. Approximately 60% of the patients were treated with medication. CONCLUSION: Quitting smoking was significantly associated with the use of medication, regardless of the profile of the smoker evaluated. In the second year of the program, quitting smoking was more strongly associated with the use of bupropion and nicotine replacement, resulting in a higher success rate and a trend toward a reduction in the relapse rate. PMID- 17268745 TI - Impact of open lung biopsy on refractory acute respiratory failure. AB - OBJECTIVE: To determine the impact that open lung biopsy findings have on decisions regarding changes in the treatment strategies employed for critically ill patients presenting diffuse pulmonary infiltrates and suffering from refractory acute respiratory failure, as well as on their clinical improvement. METHODS: This study involved 12 mechanically ventilated patients with acute respiratory failure who were subjected to open lung biopsy (by thoracotomy) after not presenting a clinical response to standard treatment. RESULTS: The single most common cause of the acute respiratory failure was viral infection, which was identified in 5 patients (40%). The pre-operative evaluation of the cause of respiratory failure was modified in 11 patients (91.6%), and a specific diagnosis was made in 100% of the cases. Regardless of changes in treatment regimen, the mortality rate was 50%. Six patients (50%) survived to be discharged from the hospital. All of the discharged patients survived for at least one year after the open lung biopsy, for an overall one-year survival rate of 50% among the 12 patients studied. For the patients who died in the hospital, the time of survival after open lung biopsy was 14 + 10.8 days. CONCLUSION: We conclude that open lung biopsy is a useful tool in the management of acute respiratory failure when there is no clinical improvement after standard treatment, since it can lead to a specific diagnosis that requires distinct treatment, which probably lowers the mortality rate among such patients. PMID- 17268746 TI - Co-infection with Mycobacterium tuberculosis and human immunodeficiency virus: an epidemiological analysis in the city of Taubate, Brazil. AB - OBJECTIVE: To discuss the main aspects of co-infection with Mycobacterium tuberculosis and human immunodeficiency virus in the city of Taubate (located in the state of Sao Paulo, Brazil) in 2001 and 2002. METHODS: This study presents epidemiological data on tuberculosis cases occurring in Taubate in 2001 and 2002. RESULTS: Of the 250 cases of tuberculosis analyzed, 70 (28%) presented human immunodeficiency virus seropositivity, 95 (38%) presented human immunodeficiency virus seronegativity, and 85 (34%) were patients who had not been submitted to serological testing. In the first group (tuberculosis and human immunodeficiency virus seropositivity), males from 30 to 40 years of age predominated, the most common clinical presentation of tuberculosis was pulmonary (65.71%), and the cure rate was 59.38%. In the group of tuberculosis patients presenting human immunodeficiency virus seronegativity, males from 30 to 40 years of age also predominated, the most common clinical presentation of tuberculosis was also pulmonary (70.55%), and the cure rate was 81.63%. CONCLUSION: We conclude that the human immunodeficiency virus plays an important role in the epidemiology of tuberculosis. Therefore, serological testing for human immunodeficiency virus should be carried out when a diagnosis of tuberculosis is made. PMID- 17268747 TI - Multidrug-resistant Mycobacterium tuberculosis at a referral center for infectious diseases in the state of Minas Gerais, Brazil: sensitivity profile and related risk factors. AB - OBJECTIVE: To assess the determining factors for Mycobacterium tuberculosis multidrug resistance at a referral center for infectious diseases in the state of Minas Gerais, Brazil. METHODS: A retrospective case-control study was conducted using data collected from September of 2000 to January of 2004. During this period, 473 cultures presenting growth of M. tuberculosis, corresponding to 313 patients, were submitted to susceptibility tests at the Central Laboratory of Minas Gerais. Cases presenting resistance to at least rifampin and isoniazid were classified as cases of multidrug resistance and were selected for study. These cases were paired to control group cases of drug-susceptible tuberculosis at a ratio of 1:3. Clinical and demographic data were analyzed using univariate and multivariate analyses. RESULTS: During the study period, 12 (3.83%) cases of multidrug-resistant tuberculosis were identified. In the univariate analysis, multidrug-resistant tuberculosis was found to be more common among male patients, as well as among those testing positive in the sputum smear microscopy, those with cavitations larger than 4 cm in diameter and those having been previously treated for tuberculosis (p = 0.10 for all). After the multivariate analysis, only previous treatment for tuberculosis remained statistically significant (p = 0.0374), with an odds ratio of 14.36 (1.96-176.46). CONCLUSION: In the present study, previous treatment for tuberculosis was found to be an independent risk factor for multidrug-resistant tuberculosis. PMID- 17268748 TI - Tuberculin testing of individuals infected with the human immunodeficiency virus: relationship with peripheral T-cell counts and active tuberculosis. AB - OBJECTIVE: To evaluate tuberculin test results and relate them to the presence or absence of active tuberculosis, as well as to CD4+ and CD8+ T-lymphocyte counts. METHOD: The charts of 802 patients with acquired immunodeficiency syndrome treated between August of 1985 and March of 2003 were reviewed. Of the 185 patients submitted to tuberculin tests (23.1%), 107 (57.8%) were male, and 78 (42.2%) were female. Patients were divided into two study groups: tuberculin test reactors (n = 28); and tuberculin test non-reactors (n = 157). Among the reactors, the mean age was 30.60 years, with a standard deviation of 6.62 years, compared with 34.45 years, with a standard deviation of 10.32 years, among the non-reactors. RESULTS: Most of the individuals tested presented only a mild response to the tuberculin test. We found that, at the time of the test, the percentage of individuals with active tuberculosis was greater in the reactor group than in the non-reactor group. During the test period, 10 reactor group patients and 11 non-reactor group patients presented some clinical form of active tuberculosis. In addition, CD4+ T-lymphocyte counts were lower than 200 cells/mm(3) in 6 reactor group patients and in 8 non-reactor group patients. CONCLUSION: Indurations greater than 5 mm were unrelated to higher absolute CD4+ T-cell counts. PMID- 17268749 TI - Tuberculosis as a disease defining acquired immunodeficiency syndrome: ten years of surveillance in Rio de Janeiro, Brazil. AB - OBJECTIVE: To analyze the frequency of tuberculosis and of the other principal opportunistic infections defining acquired immunodeficiency syndrome at the time such cases were reported in the city of Rio de Janeiro, Brazil. METHODS: Analysis of the data compiled in the Rio de Janeiro Municipal Program for the Surveillance of Sexually Transmitted Diseases and Acquired Immunodeficiency Syndrome database from 1993 to 2002. RESULTS: The expanded definition of a case of acquired immunodeficiency syndrome, implemented in 1998, resulted in a substantial increase in the number of reported cases of acquired immunodeficiency syndrome, especially of those defined by immunologic criteria. Among the cases of acquired immunodeficiency syndrome defined only by disease, esophageal candidiasis, in its various forms, remained the most common opportunistic infection present at the time the cases of acquired immunodeficiency syndrome were reported. Although Pneumocystis carinii pneumonia was the second leading opportunistic infection in most of the years evaluated, it was surpassed by tuberculosis in 2001. CONCLUSION: Despite the decreased numbers of cases of acquired immunodeficiency syndrome defined by disease, tuberculosis remains a significant acquired immunodeficiency syndrome-defining event, currently more common than P. carinii pneumonia and toxoplasmosis. This is probably due to the high rate of tuberculosis prevalence in the city. PMID- 17268750 TI - An update on the use of antifungal agents. AB - We summarize here data regarding the spectrum of action, the pharmacological aspects, the toxicological aspects and the clinical efficacy of liposomal amphotericin B, amphotericin B in colloidal dispersion, amphotericin B lipid complex, voriconazole and caspofungin. We discuss the use of these more recently introduced antifungal agents in terms of their safety, efficiency and cost. We also offer suggestions for the clinical use of these drugs in pulmonary and systemic infections, with an emphasis on the lower toxicity of the lipid formulations of amphotericin B in comparison with conventional medications. In addition, we explore the possibility of using voriconazole as the primary treatment for invasive infections such as aspergillosis, as well as those caused by Scedosporium spp. and Fusarium spp., together with that of using caspofungin to treat disseminated candidiasis and invasive aspergillosis. PMID- 17268751 TI - Nutrition therapy for chronic obstructive pulmonary disease and related nutritional complications. AB - Chronic obstructive pulmonary disease is characterized by progressive and partially reversible airway obstruction. The innumerable complications that occur during the progression of the disease can affect the nutritional state of patients suffering from this illness. The objective of this study was to present a brief review of the literature regarding the nutrition therapy used in the treatment of chronic obstructive pulmonary disease. To that end, we performed a bibliographic search for related articles published within the last 18 years and indexed for the Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS, Latin American and Caribbean Health Sciences Literature) and Medline databases. Malnutrition is associated with a poor prognosis for patients with chronic obstructive pulmonary disease, since it predisposes such patients to infections, as well as reducing respiratory muscle force, exercise tolerance and quality of life. Despite the fact that such malnutrition is extremely common in chronic obstructive pulmonary disease patients, it should be recognized as an independent risk factor, since it can be modified through appropriate and efficacious diet therapy and monitoring. For patients with chronic obstructive pulmonary disease, nutrition therapy is initiated after the evaluation of the nutritional state of the patient, which identifies nutritional risk, thereby allowing the proper level of treatment to be established. In this evaluation, anthropometric and biochemical markers, as well as indicators of dietary consumption and body composition, should be used. The prescribed diet should contain appropriate proportions of macronutrients, micronutrients and immunonutrients in order to regain or maintain the proper nutritional state and to avoid complications. The physical characteristics of the diet should be tailored to the individual needs and tolerances of each patient. In the treatment of patients with chronic obstructive pulmonary disease, individualized nutrition therapy is extremely important and has been shown to be fundamental to improving quality of life. PMID- 17268752 TI - Allergic bronchopulmonary aspergillosis presenting a glove-finger shadow in radiographic images. AB - Allergic bronchopulmonary aspergillosis is a lung disease occurring in patients with asthma or cystic fibrosis, triggered by a hypersensitivity reaction to the presence of Aspergillus fumigatus in the airways. We report herein the case of a patient presenting a clinical profile suggestive of asthma and meeting the clinical, laboratory testing and radiological criteria for a diagnosis of allergic bronchopulmonary aspergillosis. The importance of such findings is that early diagnosis can reduce the risk of respiratory exacerbations and fibrosis. PMID- 17268753 TI - Isolated pulmonary cryptococcosis in an immunocompetent patient. AB - In this study, we report a case of pulmonary cryptococcosis in a patient presenting respiratory symptoms and a lung mass on the chest X-ray. The patient had no concomitant diseases, was seronegative for human immunodeficiency virus and was not receiving immunosuppressive therapy of any kind. The diagnosis was confirmed through transbronchial biopsy and bronchoalveolar lavage. The patient was treated as an outpatient with fluconazole (300 mg/day for six months), evolving to clinical improvement and partial regression of the lung mass, as seen on a second chest X-ray. The current case illustrates an unusual presentation of pulmonary cryptococcosis and raises questions regarding the therapeutic approaches proposed in the literature. PMID- 17268754 TI - Idiopathic bilateral diaphragmatic paresis. AB - We report the case of a patient with severe dyspnea upon reclining. Lung disease, neuromuscular disorders and heart disease were ruled out. However, during the course of the investigation, bilateral diaphragmatic paresis was discovered. A key sign leading to the diagnosis was evidence of paradoxical respiration in the dorsal decubitus position. When the patient was moved from the orthostatic position to the dorsal decubitus position, oxygenation and forced vital capacity worsened. The orthostatic fluoroscopy was normal. Maximal inspiratory pressure was severely reduced. The responses to transcutaneous electric stimulation of the diaphragm were normal. However, electric stimulation of the phrenic nerve produced no response, leading to the diagnosis of bilateral diaphragmatic paresis. PMID- 17268755 TI - [Lymphocytoma cutis benigna. Case report of a 9 year old boy]. AB - Infectious conditions of the infantile genitals are a diagnostic challenge. One of the rare differential diagnoses is lymphocytoma cutis benigna. We report a case of borrelial lymphocytoma of the glans penis in a 9 year old boy. Based on this case, the clinical, diagnostic and therapeutic aspects of this rare form of dermatoborreliosis are discussed. PMID- 17268756 TI - [Quality of kidney procurement in Germany. Ten years experience and 486 renal allografts in a single centre]. AB - BACKGROUND: Organ damage during organ procurement is believed to be an increasing problem among transplant centres. However, only very few published data are available. The purpose of our study was to examine the quality of kidney procurement in Germany. METHODS: We retrospectively analyzed all allograft renal transplants performed at our centre from 1996 to 2005. All kidneys were retrieved in Germany and allocated by Eurotransplant. RESULTS: From a total of 486 cadaveric kidneys, 103 (21.2%) were not correctly retrieved. Nevertheless, none of the organs had to be rejected. In 18 (3.7%), a technically insufficient organ retrieval was associated with a considerable extension of the surgical procedure or complications. CONCLUSIONS: Technically insufficient kidney procurement rarely results in clinical consequences. However, surgeons performing organ retrieval should be better trained. Whether adequate technical proficiency is achieved with ten supervised cases, as requested by the German Medical Association, remains to be determined. In our opinion, a further interdisciplinary course that trains surgeons in more refined techniques of organ procurement is desirable. PMID- 17268757 TI - [Malignant mesothelioma of the tunica vaginalis testis]. AB - Malignant epithelioid mesothelioma of the tunica vaginalis of the testis is very rare. It is often diagnosed accidentally by histologic examination of the hydrocelectomy wall preparation. The aggressiveness and poor prognosis of this tumor require radical surgery as the primary therapy. We describe the case of a 45 year old patient, in whom an epithelioid mesothelioma was incidentally detected after hydrocelectomy. PMID- 17268758 TI - Production of poly(3-hydroxybutyric-co-3-hydroxyvaleric acid) having a high hydroxyvalerate content with valeric acid feeding. AB - The capability of different organic acids to produce a derivative of PHB [poly(3 hydroxybutyric-co-3-hydroxyvaleric acid), P(3HB-co-3HV)] was examined in shake flask cultivations. Propionic and valeric acids demonstrated the potential to produce P(3HB-co-3HV) under nitrogen limiting conditions at 30 degrees C. The addition time and the initial concentration of valeric acid needed for a high cellular HV content were identified by extensive experimentation. Fed-batch cultivation in 7-l bioreactor with valeric acid feeding resulted in the production of PHA containing 54% HV units. PMID- 17268759 TI - Finite-difference schemes for reaction-diffusion equations modeling predator-prey interactions in MATLAB. AB - We present two finite-difference algorithms for studying the dynamics of spatially extended predator-prey interactions with the Holling type II functional response and logistic growth of the prey. The algorithms are stable and convergent provided the time step is below a (non-restrictive) critical value. This is advantageous as it is well-known that the dynamics of approximations of differential equations (DEs) can differ significantly from that of the underlying DEs themselves. This is particularly important for the spatially extended systems that are studied in this paper as they display a wide spectrum of ecologically relevant behavior, including chaos. Furthermore, there are implementational advantages of the methods. For example, due to the structure of the resulting linear systems, standard direct, and iterative solvers are guaranteed to converge. We also present the results of numerical experiments in one and two space dimensions and illustrate the simplicity of the numerical methods with short programs MATLAB: . Users can download, edit, and run the codes from http://www.uoguelph.ca/~mgarvie/, to investigate the key dynamical properties of spatially extended predator-prey interactions. PMID- 17268760 TI - Assessing morale in community mental health professionals: a pooled analysis of data from four European countries. AB - BACKGROUND: While there is a need to assess morale in community mental health professionals, it still remains to be determined how to obtain and interpret data in a sound and meaningful way. The aims of the present study were to assess the extent to which levels of morale are sensitive to differences between professional groups and health care systems, and identify factors influencing morale across groups and settings. METHODS: A literature search of electronic databases was undertaken to identify studies measuring morale in different groups of community mental health professionals. Data was subjected to a pooled analysis. Differences between groups and sites were tested using factorial ANOVA and respective effect sizes were estimated based on Cohen's [1] work. RESULTS: Data of four studies and a total of 723 professionals (from Austria, Germany, Italy and United Kingdom) were combined in a pooled analysis. Significant differences of morale levels were found between professional groups and study sites, and differences between professional groups varied significantly by study site. Effect sizes estimated for differences between particular groups of different health care systems ranged from small to large. Age was found to be a factor independently associated with morale. CONCLUSIONS: Staff in community mental health care show substantial differences in morale levels depending on the professional group and context. These differences can often be identified even if in sample sizes of only 30 participants per group. Levels of morale need to be established specifically for different professional groups and context, and age should be controlled as an influential factor. The findings show a discriminant validity of assessment instruments for staff morale in community mental health care, and underline the rationale for such assessments in research and routine care. PMID- 17268761 TI - Risk factors for suicide in the immediate post-discharge period. AB - BACKGROUND: Suicide risk is highest in the first few months following psychiatric in-patient care. Most data on post-discharge suicides have come from Western countries. Many studies collected cases of suicide over a long post-discharge period and did not focus on this high-risk period. This study aims to describe the characteristics and examine the risk factors of suicides occurring in the immediate post-discharge period in Hong Kong. METHODS: A case-control study based on discharged patients from all psychiatric hospitals/units in Hong Kong in 1997 1999. Suicides occurring within 60 days of discharge from psychiatric hospitals (N = 97) were ascertained by record linkage with Coroner's court data. Controls were matched for age, gender, diagnoses, discharge hospitals, and dates of discharge. Possible risk factors were extracted from in- and out-patient records, and were identified by conditional logistic regression. RESULTS: The commonest diagnosis and suicide method were schizophrenia and falling from a height, respectively. There were no significant case-control differences in the drug treatment received. Risk factors for suicides were: previous deliberate self-harm (OR = 2.3, 95% CI = 1.07-5.05), admission for deliberate self-harm (OR = 3.2, 95% CI = 1.3-7.8), compulsory admission (OR = 3.1, 95% CI = 1.1-8.7), living alone (OR = 5.8, 95% CI = 1.4-23), work stresses (OR = 5.4, 95% CI = 1.5-18) and being out of contact (OR = 7.9, 95% CI = 1.87-33). The overall number of risk factors had greater screening efficacy for suicide than any single factor. CONCLUSIONS: Vulnerable (previous suicidality) and uncooperative (compulsory admission and out of contact) patients who live alone and are exposed to work stresses are prone to immediate post-discharge suicide. Thorough treatment of the circumstances leading to the index admissions, management of work stresses, improved engagement in follow-up care and systematic assessment of suicide risk are indicated. PMID- 17268762 TI - Ceremonies of the whole: does social participation moderate the mood consequences of neuroticism? AB - BACKGROUND: The aim of this research was to test whether social participation is associated with improvements in mood and well-being, and in particular to test whether social participation might moderate the chronic distress associated with high levels of neuroticism (N). METHOD: A rural Australian sample of 394 adults (54.3% female) completed questionnaires and participated in follow-up interviews. Social participation was indexed by community group membership, and operationalised for analysis in two forms: extent (number of group memberships) and presence (zero vs. one or more memberships). Mood was measured as Positive Affect (PA) and Negative Affect (NA) as rated on the Positive and Negative Affect Schedule and well-being was measured with Diener's Satisfaction with Life (SWL) questionnaire. Items from Goldberg's International Personality Item Pool were used to measure N. RESULTS: The extent of social participation was significantly associated with all three mood/well-being variables in bivariate analyses, and remained as a significant net predictor of PA and NA (beta = 0.11, P < 0.05, beta = -0.13, P < 0.05) when modeled with age, gender and income. In parallel, categorical social participation was found to be significantly associated with PA, NA and SWL in bivariate analyses and in multivariate analyses controlling for age, gender and income (beta = 0.11, P < 0.05, beta = -0.15, P < 0.01 and beta = 0.11, P < 0.05, respectively). The interaction term N*Social interaction was significantly correlated with NA in bivariate analyses involving both continuous (r = -0.14, P < 0.01) and categorical (r = -0.13, P < 0.01) measures of social participation, and in its continuous form remained a significant net predictor of NA after controlling for the main effects of N and Social participation (beta = 0.09, P < 0.05). CONCLUSIONS: The present findings extend upon existing evidence that social participation tends to be positively associated with mental health by demonstrating the predicted effect across a comprehensive set of mood/well-being variables. Preliminary evidence was also obtained that social participation may serve as a moderator of the chronic distress associated with N. It is concluded that further research seeking to confirm the causal direction of the identified pathways is warranted. PMID- 17268763 TI - Does the level of expressed emotion (LEE) questionnaire have the same factor structure for adolescents as it has for adults? AB - BACKGROUND: The level of expressed emotion (LEE) is a four-factor questionnaire that measures expressed emotion (EE) as perceived by the recipient. These factors are: perceived lack of emotional support, perceived intrusiveness, perceived irritation, and perceive criticism. The four factors of the LEE has previously been found to be related to psychological disorders and has good psychometric properties for adults. However, it has not previously been studied in adolescent populations. METHODS: A total of 311 adolescents participated in this study. Using structural equation modeling, confirmatory factor analyses were conducted to examine if the LEE also had the same four-factor structure for adolescents as it does for adults. RESULTS: The confirmatory factor analyses demonstrated that the LEE's four-factor structure also applied to adolescents. The internal consistency of the scales were good and all the inter-correlations between the scales were significant. Additionally, the factors were significantly correlated to adolescent depressive and anxiety symptom score dimensions. CONCLUSION: These findings seem to indicate that the LEE may be a good instrument in the measurement of adolescents perceived EE. PMID- 17268764 TI - Laser applications in oral surgery and implant dentistry. AB - Lasers have been used for many years in oral surgery and implant dentistry. In some indications, laser treatment has become state of the art as compared to conventional techniques. This article is a comprehensive review of new laser applications in oral surgery and implant dentistry. One of the most interesting developments over the last years was the introduction of the 9.6-microm CO(2) laser. It has been shown in the recent literature that the use of this new device can preserve tissue with almost no adverse effects at the light microscopic level. In contrast, modifications of approved CO(2) laser therapies of premalignant lesions resulted in higher recurrence rates than the conventional defocused laser technique. However, several studies indicate that other wavelengths such as Nd-YAG (lambda = 1,064 nm) or diode lasers (lambda = 810 nm) may be also of value in this field. In many other indications, the use of lasers is still experimental. Intraoperatively used photodynamic therapy or peri-implant care of ailing implants with the CO(2) laser seems to be more of value than conventional methods. However, further studies are required to assess standard protocols. Over the past years, research identified some new indications for laser treatment in oral surgery and implant dentistry. Moreover, well-known laser applications were defined as state of the art. Nevertheless, further studies are required for laser treatment in oral surgery and implant dentistry. PMID- 17268765 TI - Mathematical modeling of selective photothermolysis to aid the treatment of vascular malformations and hemangioma with pulsed dye laser. AB - Pulsed dye lasers (PDL) are the standard of care in the treatment of cutaneous vascular disorders such as the port-wine strains or hemangiomas of infancy. Nonetheless, there is still uncertainty regarding the specific laser parameters that are likely to yield optimal clinical outcomes. Using mathematical modeling, we explain and associate clinical outcomes with laser wavelength, radiant exposure, and pulse time and shape. The model's prediction that a continuous PDL pulse of 0.45 ms with a radiant exposure of 6 J/cm(2) is equivalent to delivering a 1.5-ms pulse consisting of three pulses with a radiant exposure of 12 J/cm(2) is in agreement with clinical studies. The model also suggests that for vascular malformations involving vessel diameters in the range of 150-500 microm, one should use a PDL at a wavelength of 595 nm with a radiant exposure of at least 12 J/cm(2) and pulse time of 1.5 ms, delivered in three pulses. Whereas it is calculated that malformations with vessels smaller than 50 microm will not respond to PDL in any clinical setting, an excellent response to PDL treatment at either a 585- or 595-nm wavelength can be expected for malformations with vessel diameters of 50-150 microm. Epidermal cooling is highly recommended for all settings to minimize pain and the risk of side effects. Finally, the model is used to generate a reference table that suggests specific PDL parameters for the treatment of various malformations and hemangiomas. The table cannot replace a clinician's experience with respect to which and how parameters should be changed, but provides a defined window of parameters that should be tried to improve clinical response. PMID- 17268766 TI - Assessment of TVT efficacy in the management of patients with genuine stress incontinence with the use of epidural vs intravenous anesthesia. AB - Our aim was to validate the use of intravenous anesthesia as an alternative to epidural anesthesia for the placement of tension-free vaginal tape (TVT) in patients with urodynamic stress incontinence. Eighty-six patients participated in this prospective study. Forty-five patients were operated with intravenous anesthesia and 41 patients with epidural anesthesia. All patients had a full history taken and a complete gynecological examination performed at initial visit. Preoperative and postoperative urodynamic investigations included filling and voiding cystometry, urethral profilometry, uroflow, and cough stress test. Genuine stress incontinence diagnosis was based on the findings of urodynamic investigations. Patients with prolapse more than first degree or detrusor instability were excluded from the study. The objective success rate for patients operated with intravenous anesthesia was 86.6%, whereas for patients operated with epidural anesthesia was 88% at 12 months of follow-up. We had no cases of postoperative bleeding or hematoma development. Postoperative urinary tract infection developed in three cases (3 of 74). Application of TVT procedure with intravenous anesthesia provides comparable results with the use of epidural anesthesia and could be a very good alternative. PMID- 17268768 TI - Extreme arsenic resistance by the acidophilic archaeon 'Ferroplasma acidarmanus' Fer1. AB - 'Ferroplasma acidarmanus' Fer1 is an arsenic-hypertolerant acidophilic archaeon isolated from the Iron Mountain mine, California; a site characterized by heavy metals contamination. The presence of up to 10 g arsenate per litre [As(V); 133 mM] did not significantly reduce growth yields, whereas between 5 and 10 g arsenite per litre [As(III); 67-133 mM] significantly reduced the yield. Previous bioinformatic analysis indicates that 'F. acidarmanus' Fer1 has only two predicted genes involved in arsenic resistance and lacks a recognizable gene for an arsenate reductase. Biochemical analysis suggests that 'F. acidarmanus' Fer1 does not reduce arsenate indicating that 'F. acidarmanus' Fer1 has an alternative resistance mechanism to arsenate other than reduction to arsenite and efflux. Primer extension analysis of the putative ars transcriptional regulator (arsR) and efflux pump (arsB) demonstrated that these genes are co-transcribed, and expressed in response to arsenite, but not arsenate. Two-dimensional polyacrylamide gel electrophoresis analysis of 'F. acidarmanus' Fer1 cells exposed to arsenite revealed enhanced expression of proteins associated with protein refolding, including the thermosome Group II HSP60 family chaperonin and HSP70 DnaK type heat shock proteins. This report represents the first molecular and proteomic study of arsenic resistance in an acidophilic archaeon. PMID- 17268769 TI - On the relations between affordance and representation of the agent's effector. AB - The present study aimed to determine whether the representation of object affordances requires specification of the effector potentially interacting with the object: specifically, in this study, vision of the interacting hand. In Experiment 1 we used an apparatus by which a fruit to be reached and grasped was identified by word reading, whereas another (interfering) fruit was visually perceived at the same location as the target. The apparatus allowed visual presentation of the agent's interacting hand or prevented it. When visually presented, the hand was perceived as still at the start position even when it moved to grasp the fruit. An interference effect on the grasp congruent with the distractor size was observed only when the hand was visible. In Experiment 2, interference was observed also when a hand different from the agent's own was visually presented. In both Experiments 1 and 2 the visible fruit interfered with the arm's reach, but the effect was independent of its size and less dependent on the visually-presented hand. A control experiment (Experiment 3) enabled comparison of the interference of visual stimuli on targets identified by word reading (Experiments 1 and 2) with that of objects identified by word reading on visually-presented targets (Experiment 3). The interference induced by visual stimuli was stronger than the interference induced by objects identified by words (i.e. affordances evoked by visual stimuli were stronger than affordances evoked by semantics). Taken together, the results of the present study suggest that the specification of the agent's effector is necessary for the elicitation of affordances. However, the elicitation of these affordances was observed for interactions between object and hand (grasp), rather than for interactions between object and arm (reach). Finally, our data confirm the influence of semantics on the control of arm movements, though less strong than that due to visual input. PMID- 17268770 TI - Insights into male germ cell apoptosis due to depletion of gonadotropins caused by GnRH antagonists. AB - The role of pituitary gonadotropins in the regulation of spermatogenesis has been unequivocally demonstrated, although, the precise mechanism of this regulation is not clearly understood. Previous studies have shown that specific immunoneutralization of LH/testosterone caused apoptotic cell death of meiotic and post-meiotic germ cells while that of FSH resulted in similar death of meiotic cells. In the present study, the death process of germ cells has been characterized by depleting both FSH and testosterone by administering two different potent GnRH antagonists, Cetrorelix and Acyline to both rats and mice. Pro-survival factors like Bcl-2 and Bcl-x/l were unaltered in germ cells due to GnRH antagonist treatment, although a significant increase in several pro apoptotic markers including Fas and Bax were evident at both protein and RNA levels. This culminated in cytochrome C release from mitochondria and eventually increase in the activity of caspase-8 and caspase-3. These data suggest that both extrinsic and intrinsic apoptotic death pathways are operative in the germ cells death following decrease in FSH and testosterone levels. Multiple injections of GnRH antagonist resulted in complete disappearance of germ cells except the spermatogonial cells and discontinuation of the treatment resulted in full recovery of spermatogenesis. In conclusion our present data suggest that the principal role of FSH and testosterone is to maintain spermatogenic homeostasis by inhibiting death signals for the germ cells. PMID- 17268771 TI - Delayed mitochondrial dysfunction in apoptotic hair cells in chinchilla cochleae following exposure to impulse noise. AB - Apoptotic death of hair cells (HCs) in the cochlea has been found following exposure to intense noise. The current study was designed to examine the mitochondrial energetic function of HCs during the course of noise-induced apoptosis. Two aspects of the mitochondrial energetic function, succinate dehydrogenase (SDH) activity and mitochondrial membrane potential (MMP), were examined in HCs of chinchilla cochleae following exposure to a series of 75 pairs of impulse noises at 155 dB pSPL. The results showed that nuclear condensation and uptake of propidium iodide or trypan blue appeared at 10 min after the noise exposure, indicating a rapid progression of HC apoptosis. However, SDH activity was preserved at this time point. As the time elapsed (1 hr or 24 hrs) after the noise exposure, all newly-generated apoptotic HCs showed strong SDH activity, indicating the preservation of SDH activity during the course of apoptosis. Examination of MMP with rhodamine 123 staining revealed that MMP was sustained in the apoptotic HCs having mild nuclear condensation, even after the occurrence of cell membrane leakage. MMP was reduced with further progression of nuclear condensation. These results suggest the presence of a delayed mitochondrial dysfunction in apoptotic HCs following exposure to intense noise. PMID- 17268772 TI - Neuronal imaging using SPECT. AB - BACKGROUND: 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is one of only a few methods available for objective evaluation of cardiac sympathetic function at a clinical level. Disorders in cardiac sympathetic function play an important role in various heart diseases, and MIBG provides an abundance of useful information for evaluation of disease severity, prognosis, and therapeutic effects; this information is of particular value in patients with heart failure, ischemic heart diseases, or arrhythmic disorders. On the other hand, the quantitative indices for MIBG differ between institutions, and evidence has not been sufficiently well established for MIBG, compared with myocardial perfusion imaging, in ischemic heart diseases. REVIEW: In view of these difficulties, this review provides fundamental information regarding MIBG, its usefulness for various diseases and future difficulties. PMID- 17268774 TI - Sample preparation of sewage sludge and soil samples for the determination of polycyclic aromatic hydrocarbons based on one-pot microwave-assisted saponification and extraction. AB - A microwave-assisted sample preparation (MASP) procedure was developed for the analysis of polycyclic aromatic hydrocarbons (PAHs) in sewage sludge and soil samples. The procedure involved the simultaneous microwave-assisted extraction of PAHs with n-hexane and the hydrolysis of samples with methanolic potassium hydroxide. Because of the complex nature of the samples, the extracts were submitted to further cleaning with silica and Florisil solid-phase extraction cartridges connected in series. Naphthalene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[e]pyrene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, benzo[g,h,i]perylene, and indeno[1,2,3-cd]pyrene, were considered in the study. Quantification limits obtained for all of these compounds (between 0.4 and 14.8 microg kg(-1) dry mass) were well below of the limits recommended in the USA and EU. Overall recovery values ranged from 60 to 100%, with most losses being due to evaporation in the solvent exchange stages of the procedure, although excellent extraction recoveries were obtained. Validation of the accuracy was carried out with BCR-088 (sewage sludge) and BCR-524 (contaminated industrial soil) reference materials. PMID- 17268775 TI - Preparation and characterization by surface-enhanced infrared absorption spectroscopy of silver nanoparticles formed on germanium substrates by electroless displacement. AB - In this paper, the feasibility of applying electroless displacement to prepare silver nanoparticles (AgNPs) on the surface of germanium (Ge) substrate is demonstrated, and the performances of surfaces prepared in this manner for surface-enhanced infrared absorption (SEIRA) spectroscopy are reported. The process used to produce suitable AgNPs for SEIRA by electroless deposition is simple and effective, requiring only pretreatment of the germanium surface with hot air, immersion of the substrate in a dilute solution of silver nitrate, and washing of the resulting plate. To quantify the behavior of AgNPs on a Ge substrate and to optimize the conditions for the preparation of AgNPs on Ge substrates, a monolayer of p-nitrothiophenol (PNTP) was bonded to the surface of the AgNPs by immersion of the plate in a dilute solution of PNTP and measurement of the transmission spectrum. The factors that influenced the formation of AgNPs, and hence the SEIRA signals, included the concentration of AgNO3, the reaction time and the temperature. Results indicated that stronger absorption bands in the SEIRA spectrum of a monolayer of PNTP were obtained if the reaction rate for the displacement of silver ions by Ge was slow. This condition was achieved by keeping the concentration of AgNO3 and the reaction temperature low. Under the optimal conditions found in this work, an enhancement factor of approximately 100 was achieved for commonly used probe molecules in SEIRA measurements. PMID- 17268773 TI - Clinical radionuclide therapy dosimetry: the quest for the "Holy Gray". AB - INTRODUCTION: Radionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy. REVIEW: This review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose-response relationship. To prove that dosimetry based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce. DEVELOPMENTS: In each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally. PMID- 17268777 TI - Development of a 100 nmol mol(-1) propane-in-air SRM for automobile-exhaust testing for new low-emission requirements. AB - New US federal low-level automobile emission requirements, for example zero-level emission vehicle (ZLEV), for hydrocarbons and other species, have resulted in the need by manufacturers for new certified reference materials. The new emission requirement for hydrocarbons requires the use, by automobile manufacturing testing facilities, of a 100 nmol mol(-1) propane in air gas standard. Emission measurement instruments are required, by federal law, to be calibrated with National Institute of Standards and Technology (NIST) traceable reference materials. Because a NIST standard reference material (SRM) containing 100 nmol mol(-1) propane was not available, the US Environmental Protection Agency (EPA) and the Automobile Industry/Government Emissions Research Consortium (AIGER) requested that NIST develop such an SRM. A cylinder lot of 30 gas mixtures containing 100 nmol mol(-1) propane in air was prepared in 6-L aluminium gas cylinders by a specialty gas company and delivered to the Gas Metrology Group at NIST. Another mixture, contained in a 30-L aluminium cylinder and included in the lot, was used as a lot standard (LS). Using gas chromatography with flame ionization detection all 30 samples were compared to the LS to obtain the average of six peak-area ratios to the LS for each sample with standard deviations of <0.31%. The average sample-to-LS ratio determinations resulted in a range of 0.9828 to 0.9888, a spread of 0.0060, which corresponds to a relative standard deviation of 0.15% of the average for all 30 samples. NIST developed its first set of five propane in air primary gravimetric standards covering a concentration range 91 to 103 nmol mol(-1) with relative uncertainties of 0.15%. This new suite of propane gravimetric standards was used to analyze and assign a concentration value to the SRM LS. On the basis of these data each SRM sample was individually certified, furnishing the desired relative expanded uncertainty of +/-0.5%. Because automobile companies use total hydrocarbons to make their measurements, it was also vital to assign a methane concentration to the SRM samples. Some of the SRM samples were analyzed and found to contain 1.2 nmol mol(-1) methane. Twenty-five of the samples were certified and released as SRM 2765. PMID- 17268776 TI - Biomolecular profiling of metastatic prostate cancer cells in bone marrow tissue using FTIR microspectroscopy: a pilot study. AB - Prostate cancer (CaP) cells preferentially metastasise to the bone marrow, a microenvironment that plays a substantial role in the sustenance and progression of the CaP tumour. Here we use a combination of FTIR microspectroscopy and histological stains to increase molecular specificity and probe the biochemistry of metastatic CaP cells in bone marrow tissue derived from a limited source of paraffin-embedded biopsies of different patients. This provides distinction between the following dominant metabolic processes driving the proliferation of the metastatic cells in each of these biopsies: glycerophospholipid synthesis from triacylglyceride, available from surrounding adipocytes, in specimen 1, through significantly high (p < or = 0.05) carbohydrate (8.23 +/- 1.44 cm(-1)), phosphate (6.13 +/- 1.5 cm(-1)) and lipid hydrocarbon (24.14 +/- 5.9 cm(-1)) signals compared with the organ-confined CaP control (OC CaP), together with vacuolation of cell cytoplasm; glycolipid synthesis in specimen 2, through significantly high (p < or = 0.05) carbohydrate (5.51 +/- 0.04 cm(-1)) and high lipid hydrocarbon (17.91 +/- 2.3 cm(-1)) compared with OC CaP, together with positive diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells; glycolysis in specimen 3, though significantly high (p < or = 0.05) carbohydrate (8.86 +/- 1.78 cm(-1)) and significantly lower (p < or = 0.05) lipid hydrocarbon (11.67 +/- 0.4 cm(-1)) than OC CaP, together with negative diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells. Detailed understanding of the biochemistry underpinning the proliferation of tumour cells at metastatic sites may help towards refining chemotherapeutic treatment. PMID- 17268778 TI - Interpretation of fluorescence decay kinetics in 3-methylbenzimidazolyl(5' 5')guanosine dinucleotides: exponential dependence on the number of phosphates in the polyphosphate bridge. AB - The number of phosphate groups in the 5',5'-polyphosphate bridge of mRNA-cap dinucleotide analogues affects kinetics of long-range electron transfer (ET) responsible for 3-methylbenzimidazole (m(3)B) fluorescence quenching in model dinucleotides. For instance, 3-methylbenzimidazolyl(5'-5')guanosine dinucleotides (m(3)Bp( n )G, n = 2, 3, 4) having m(3)B donor, 5'-5' polyphosphate bridge, and guanine (G) acceptor, exhibit exponential dependence of the ET rate on the number of phosphates, i.e. donor-acceptor distance. Involvement of the 5'-5' polyphosphate bridge in the ET is strongly indicated by lack of m(3)B-G stacking effect on the exponential factor, which is the same at 20 degrees C, where m(3)B G intramolecular stacking dominates, as that at 75 degrees C where stacking unstacking equilibrium is shifted in favour of the unstacked structure. PMID- 17268780 TI - CT demonstration of omovertebral bone. PMID- 17268779 TI - Accuracy of radiographer reporting of paediatric brain CT. AB - BACKGROUND: Radiographer reporting has been studied for plain films and for ultrasonography, but not in paediatric brain CT in the emergency setting. OBJECTIVE: To study the accuracy of radiographer reporting in paediatric brain CT. MATERIALS AND METHODS: We prospectively collected 100 paediatric brain CT examinations. Films were read from hard copies using a prescribed tick sheet. Radiographers with 12 years' and 3 years' experience, respectively, were blinded to the history and were not trained in diagnostic film interpretation. The radiographers' results were compared with those of a consultant radiologist. Three categories were defined: abnormal scans, significant abnormalities and insignificant abnormalities. RESULTS: Both radiographers had an accuracy of 89.5% in reading a scan correctly as abnormal, and radiographer 1 had a sensitivity of 87.8% and radiographer 2 a sensitivity of 96%. Radiographer 1 had an accuracy in detecting a significant abnormality of 75% and radiographer 2 an accuracy of 48.6%, and the sensitivities for this category were 61.6% and 52.9%, respectively. Results for detecting the insignificant abnormalities were poorer. CONCLUSIONS: Selected radiographers could play an effective screening role, but lacking the sensitivity required for detecting significant abnormality, they could not be the final diagnostician. We recommend that the study be repeated after both radiographers have received formal training in interpretation of paediatric brain CT. PMID- 17268781 TI - Optimized EPI for fMRI studies of the orbitofrontal cortex: compensation of susceptibility-induced gradients in the readout direction. AB - OBJECT: Most functional magnetic resonance imaging (fMRI) studies record the blood oxygen level-dependent (BOLD) signal using gradient-echo echo-planar imaging (GE EPI). EPI can suffer from substantial BOLD sensitivity loss caused by magnetic field inhomogeneities. Here, BOLD sensitivity losses due to susceptibility- induced gradients in the readout (RO) direction are characterized and a compensation approach is developed. MATERIALS AND METHODS: Based on a theory describing the dropout mechanism, an EPI sequence was optimized for maximal BOLD sensitivity in the orbitofrontal cortex (OFC) using a specific combination of an increased spatial resolution in the RO direction and a reduced echo time. Using measured BOLD sensitivity maps and a breath hold experiment, the model and compensation approach were tested. RESULTS: Using typical fMRI EPI parameters, susceptibility-induced gradients in the RO direction caused dropouts in the OFC and the inferior temporal lobe. Optimizing the echo time and spatial resolution effectively reduced the dropout as predicted by the theory. CONCLUSION: The model-based compensation approach effectively reduces BOLD sensitivity losses due to susceptibility-induced gradients in the RO direction. It retains the high temporal resolution of single-shot EPI and can be readily combined with methods for the compensation of susceptibility-induced field gradients in the phase-encoding and through-plane direction. PMID- 17268782 TI - An iron-based T1 contrast agent made of iron-phosphate complexes: in vitro and in vivo studies. AB - A new iron-based T1 contrast agent consisting of a complex of iron ions coordinated to phosphate and amine ligands (Fe(phos) in short) has been characterized by spectroscopic and magnetic measurements. NMR relaxation studies showed r1 values to be dependent on the phosphate salt concentration, K2HPO4, present in the medium. r1 reaches a maximum value of 2.5 mM(-1) s(-1) for measurements carried out at 7 T and 298 K. 31P MRS, Mossbauer spectroscopy and magnetic measurements of Fe(phos) solutions suggest paramagnetic Fe3+ ions present in the studied iron-phosphate complex. In vitro and in vivo toxicity experiments with C6 cells and CD1 mice, respectively, demonstrated lack of toxicity for Fe(phos) at the highest dose tested in the MRI experiments (12 mM iron for C6 cells and 0.32 mmol iron/kg for mice). Finally, T1 weighted images of brain tumours in mice have shown positive contrast enhancement of Fe(phos) for tumour afflicted regions in the brain. PMID- 17268783 TI - Cloning of srfA operon from Bacillus subtilis C9 and its expression in E. coli. AB - The srfA operon is required for the nonribosomal biosynthesis of the cyclic lipopeptide, surfactin. The srfA operon is composed of the four genes, srfAA, srfAB, srfAC, and srfAD, encoding the surfactin synthetase subunits, plus the sfp gene that encodes phosphopantetheinyl transferase. In the present study, 32 kb of the srfA operon was amplified from Bacillus subtilis C9 using a long and accurate PCR (LA-PCR), and ligated into a pIndigoBAC536 vector. The ligated plasmid was then transformed into Escherichia coli DH10B. The transformant ET2 showed positive signals to all the probes for each open reading frame (ORF) region of the srfA operon in southern hybridization, and a reduced surface tension in a culture broth. Even though the surface-active compound extracted from the E. coli transformant exhibited a different R(f) value of 0.52 from B. subtilis C9 or authentic surfactin (R(f) = 0.63) in a thin layer chromatography (TLC) analysis, the transformant exhibited a much higher surface-tension-reducing activity than the wild-type strain E. coli DH10B. Thus, it would appear that an intermediate metabolite of surfactin was expressed in the E. coli transformant harboring the srfA operon. PMID- 17268784 TI - Natural history and experimental evolution of the genetic code. AB - The standard genetic code is a set of rules that relates the 20 canonical amino acids in proteins to groups of three bases in the mRNA. It evolved from a more primitive form and the attempts to reconstruct its natural history are based on its present-day features. Genetic code engineering as a new research field was developed independently in a few laboratories during the last 15 years. The main intention is to re-program protein synthesis by expanding the coding capacities of the genetic code via re-assignment of specific codons to un-natural amino acids. This article focuses on the question as to which extent hypothetical scenarios that led to codon re-assignments during the evolution of the genetic code are relevant for its further evolution in the laboratory. Current attempts to engineer the genetic code are reviewed with reference to theoretical works on its natural history. Integration of the theoretical considerations into experimental concepts will bring us closer to designer cells with target engineered genetic codes that should open not only tremendous possibilities for the biotechnology of the twenty-first century but will also provide a basis for the design of novel life forms. PMID- 17268785 TI - DNA-fingerprinting (AFLP and RFLP) for genotypic identification in species of the Pleurotus eryngii complex. AB - Wild populations of edible species are important source of genetic variability for cultivated lines that can undergo a drastic loss of diversity resulting from man's selection. The development of tools aimed at the clear-cut and safe identification and assessment of genetic variability of the wild and cultivated strains is thus a fundamental goal of molecular genetic research. In this study, we used two polymerase chain reaction (PCR)-based fingerprinting methods amplified fragment length polymorphism (AFLP) and restriction fragment length polymorphism (RFLP) of laccase and manganese peroxidase genes-to assess genetic differences among strains and independently evolving lineages belonging to the Pleurotus eryngii complex. Both laccase RFLP and AFLP have been proved to distinguish unambiguously the three taxa studied: Pleurotus ferulae, P. eryngii, and P. eryngii var. nebrodensis. AFLP also showed enough sensitivity to detect polymorphisms among the strains, proving to be an efficient DNA fingerprinting tool in studies of strain assignment. The divergent RFLP laccase and manganese peroxidase patterns are also discussed in relation to the role played by these genes in the interaction between these fungi and their host plants. PMID- 17268786 TI - [Complex dietary measures and pharmacotherapy for metabolic syndrome]. AB - Metabolic syndrome is characterized by a group of risk factors (obesity, glucose metabolism disorders, dyslipidemia and hypertension) which appear to be caused by obesity related mechanisms of cellular metabolism and the systemic energy balance. A fibre poor diet rich in fat combined with lack of physical activity are important causative factors. A suitable change in diet combined with regular physical exercise and a moderate weight loss of about 5% leads to a massive reduction in the consequential disease diabetes type 2 by 60% in pre-diabetics and reduces the risk factors for metabolic syndrome. Pharmacological therapies using metformin or acarbose were about half as effective in reducing new cases of diabetes, while thiazolidinedione also led to a 60% reduction in new diabetes cases in pre-diabetics in spite of a weight increase. A sensible and realizable change in lifestyle provides a highly efficient therapy of metabolic syndrome, in addition to effective pharmacological options. PMID- 17268787 TI - [Urgent indications for spinal surgery in patients with rheumatoid inflammation]. AB - The urgency of spinal procedures for rheumatoid inflammatory disease is presented in three typical spinal involvements. Characteristic connections between rheumatoid arthritis and the cervical spine, spinal fractures in ankylosing spondylitis and the occurrence of bacterial spondylodiscitis as a side effect of immunosuppression are discussed. PMID- 17268788 TI - [Associated diseases and differential diagnostic considerations in childhood atopic eczema]. AB - Atopic eczema (AE) is a chronic inflammatory skin disease which affects 10 to 20% of children and 1 to 3% of adults. AE is usually diagnosed based on standard criteria such as those of Hanifin and Rajka, whereby the age-related variation must be considered. There are numerous other diseases which go along with AE or show a very similar clinical picture and represent important differential diagnostic considerations including parasitic diseases, immunodeficiency, nutritional diseases, certain neoplastic disorders and various corneal abnormalities. Additionally, it is important to consider diseases which can occur in association with AE, such as keratosis pilaris, alopecia areata or sweat disturbances. PMID- 17268789 TI - [Neurologic and neuromuscular functional disorders of the pharynx and esophagus]. AB - Neurologic swallowing disorders are an increasing diagnostic problem in our overaged population. Undiagnosed chronic aspiration pneumonia is the cause of death in 20-40% of all inhabitants of nursing homes. In neurologic diseases of the pharynx, the physiologic interaction of pharyngeal contraction, closure of the pharynx, and esophageal motility are frequently disturbed. This may be due to cortical, bulbar, or cerebellar brain damage of ischemic or traumatic origin. Furthermore diseases or peripheral nerves, muscles, and synapses cause disturbances. The most life-threatening complication of these disturbances is tracheal aspiration, which requires an iso-osmolar contrast medium for imaging studies that cause no or minimal pulmonary problems. Utilizing fast dynamic documentation we can analyze the swallowing act in 35 images within the passage time of 0.7 s. This requires digital frame sequences from 15-50 images/s, which can be provided by DSI or videofluoroscopy. Neurologic and neuromuscular patterns are demonstrated with and without tracheal aspiration. The differentiation of aspiration in a so-called pre-, intra-, and postdeglutitive form is possible. We distinguish four grades of severity of aspiration, which is also of great clinical impact for the differential rehabilitation therapy. The efficiency of the rehabilitation protocol can be assessed by the dynamic swallowing studies. PMID- 17268790 TI - [Gender differences in self-descriptions of child psychopathology in attention deficit hyperactivity disorder]. AB - Diagnosing attention deficit hyperactivity disorder (ADHD) in adults requires retrospective assessment of ADHD symptoms in childhood. The Wender Utah Rating Scale (WURS) and its German validated version (WURS-k) may offer a helpful tool to acertain relevant childhood problems associated with ADHD. Up to now validating data of the WURS-k were limited to male population. In a population of 69 female adult ADHD patients and 97 controls, ROC analysis indicated a sensitivity of 93% and specificity of 92% at a cut-off of 30 points in the WURS k. This cut-off value is equivalent to those of males. Symptom report varies significantly by gender and females describe more internalizing problems while males report more externalizing behaviour. Regarding different subtypes according to DSM-IV males and females did not differ in the items of the WURS-k. PMID- 17268792 TI - Increase in CD30 ligand/CD153 and TNF-alpha expressing mast cells in basal cell carcinoma. AB - Mast cells are a significant source of tumor necrosis factor (TNF) superfamily members, such as TNF-alpha, CD30 ligand/CD153 (CD30L) and CD40L/CD154. Furthermore, the expression of some of these proteins in mast cells has been associated with tumorigenesis, and mast cells have been found to be increased in number in the basal cell carcinoma (BCC) lesion. In this study, we have examined the expression of TNF-alpha, CD30L and CD40L immunoreactivity in mast cells in the healthy-looking skin and lesional skin of ten patients with superficial spreading BCC. Also, the counterparts of these molecules, TNF receptor (TNFR) I and II as well as CD30 and CD40, were analysed immunohistochemically. We found that numbers of mast cells and Kit-positive cells were significantly increased in the dermal BCC lesion. The percentage of CD30L-positive mast cells and the number of CD30-positive cells were significantly increased in the upper dermis of the BCC lesion as well. In addition, the numbers of TNF-alpha-positive mast cells and cells with TNFRI and TNFRII were markedly increased in the upper lesional dermis. In contrast, no mast cells positive for CD40L could be detected, even though the lesional dermis contained increased numbers of CD40 positive cells. The BCC epithelium was positive for TNFRI, TNFRII and CD40, but not for CD30, though the larger basal buds appeared to be less intensely stained for TNFRI and CD40. In conclusion, mast cells positive for CD30L and TNF-alpha, but not CD40L, are increased in number in the lesional dermis in BCC. These data suggest plausible pathways whereby mast cells can be activated and to interact with other cells and thereby contribute to the tumorigenesis in BCC. PMID- 17268791 TI - [Plasma exchange as a therapeutic option in neurological disorders]. AB - Plasma exchange is a therapeutic procedure commonly used in various neurological disorders. Here we review its current role as a treatment option in diseases of the central and peripheral nervous system. PMID- 17268793 TI - Dendritic cells loaded with polyomavirus VP1/VP2Her2 virus-like particles efficiently prevent outgrowth of a Her2/neu expressing tumor. AB - One immunization with murine polyomavirus (MPyV) VP1 virus-like particles containing a fusion protein between MPyV VP2 and the extra cellular and transmembrane domain of Her2 (Her2(1-683)PyVLPs) efficiently protects BALB/c mice from outgrowth of the Her2 expressing tumor D2F2/E2. To possibly enhance the anti Her2 immune response and abrogate the induced anti-VLP antibody response, immunization with murine dendritic cells (DCs) loaded with Her2(1-683)PyVLPs was performed. Mice were immunized once or more with 5 or 50 microg Her2(1-683)PyVLPs alone or loaded on DCs, and challenged 14 days after the last immunization with a lethal dose of Her2-positive D2F2/E2 cells. Mice were protected from tumor outgrowth, when immunized only once with 5 or 50 mug Her2(1-683)PyVLPs loaded on DCs, or 50 mug of Her2(1-683)PyVLPs alone, whereas immunization once or more with 5 mug of Her2(1-683)PyVLPs alone only protected half of the mice. Immunization with recombinant Her2 protein alone, or loaded on DCs, did not induce tumor immunity. Using both immunization strategies, Her2-specific T cell immunity was demonstrated, while Her2-specific antibodies were not detected. Loading VLPs on DCs reduced anti-VLP antibodies sixfold, but did not influence the efficiency of subsequent immunizations. Notably, DC maturation by Her2(1-683)PyVLPs in vitro was not demonstrated although the IL-12 production was significantly increased. In conclusion, loading of VLPs on DCs can enhance specific VLP immunization considerably. PMID- 17268794 TI - [Cardiopulmonary resuscitation after heroin intoxication and hypothermia]. AB - We present the case of a 21-year-old female drug addict with severe accidental hypothermia (core body temperature 27.5 degrees C) and cardiorespiratory arrest. After successful cardiopulmonary resuscitation the patient was actively internally rewarmed without the use of extracorporal circulation. Although at the first clinical presentation the patient appeared to be dead, an excellent neurological outcome was achieved. This case report reviews the epidemiology, pathophysiology, prognostic markers and the therapeutic approaches of severe hypothermia. PMID- 17268795 TI - Is there a safe plateau pressure in ARDS? The right heart only knows. AB - OBJECTIVE: Airway pressure limitation is now a largely accepted strategy in adult respiratory distress syndrome (ARDS) patients; however, some debate persists about the exact level of plateau pressure which can be safely used. The objective of the present study was to examine if the echocardiographic evaluation of right ventricular function performed in ARDS may help to answer to this question. DESIGN AND PATIENTS: For more than 20 years, we have regularly monitored right ventricular function by echocardiography in ARDS patients, during two different periods, a first (1980-1992) where airway pressure was not limited, and a second (1993-2006) where airway pressure was limited. By pooling our data, we can observe the effect of a large range of plateau pressure upon mortality rate and incidence of acute cor pulmonale. RESULTS: In this whole group of 352 ARDS patients, mortality rate and incidence of cor pulmonale were 80 and 56%, respectively, when plateau pressure was > 35 cmH(2)O; 42 and 32%, respectively, when plateau pressure was between 27 and 35 cmH(2)O; and 30 and 13%, respectively, when plateau pressure was < 27 cmH(2)O. Moreover, a clear interaction between plateau pressure and cor pulmonale was evidenced: whereas the odd ratio of dying for an increase in plateau pressure from 18-26 to 27-35 cm H(2)O in patients without cor pulmonale was 1.05 (p = 0.635), it was 3.32 in patients with cor pulmonale (p < 0.034). CONCLUSION: We hypothesize that monitoring of right ventricular function by echocardiography at bedside might help to control the safety of plateau pressure used in ARDS. PMID- 17268796 TI - Prevalence and incidence rate of diabetes mellitus in a Swedish community during 30 years of follow-up. AB - AIMS/HYPOTHESIS: Increasing diabetes prevalence has been reported in most European countries in the last 20 years. In this study we report on the development of prevalence and incidence of diabetes from 1972 to 2001 in Laxa, a rural community in central Sweden. MATERIALS AND METHODS: A diabetes register was established at the primary healthcare centre (PHCC) in Laxa, beginning in 1972 and based on data from clinical records at the PHCC, nearby hospitals and private practitioners in the area. In addition, case-finding procedures involving 85% of the residents aged 35 to 79 years old was performed from 1983 onwards. RESULTS: During the study period a total of 776 new diabetes cases was found, 36 type 1 diabetes mellitus and 740 type 2 diabetes mellitus. The age-standardised incidence rates for type 1 diabetes mellitus and type 2 diabetes mellitus were 0.15 and 3.03 cases per 1,000 population, respectively. No increase in incidence over time was detected for either forms of diabetes. Age-standardised prevalence for women and men increased from 28.3 and 25.9, respectively, per 1,000 in 1972 to 45 and 46.3 per 1,000 in 1988 (p < 0.0001), thereafter falling to a mean of 43.5 per 1,000 for women, while men had a mean of 44.9 per 1,000 for the rest of the study period. CONCLUSIONS/INTERPRETATION: The prevalence of diabetes mellitus in Laxa is high, but has not increased during the last 13 years. The incidence rate was relatively stable over the whole 30-year period. PMID- 17268797 TI - Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. AB - AIMS/HYPOTHESIS: Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. METHODS: Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid induced apoptosis. RESULTS: We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. CONCLUSIONS/INTERPRETATION: Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure. PMID- 17268798 TI - Experimental investigation on the choice of the tungsten/rhodium anode/filter combination for an amorphous selenium-based digital mammography system. AB - The signal difference-to-noise ratio (SDNR) between aluminium sheets and a homogeneous background was measured for various radiation qualities and breast thicknesses to determine the optimal radiation quality when using a Novation DR mammography system. Breast simulating phantoms, with a thickness from 2 cm to 7 cm, and aluminium sheet, with a thickness of 0.2 mm, were used. Three different combinations of anode/filter material and a wide range of tube voltages were employed for each phantom thickness. Each radiation quality was studied using three different dose levels. The tungsten (W) anode and rhodium (Rh) filter combination achieved the specified SDNR at the lowest mean glandular dose for all the phantom thicknesses and X-ray tube voltages. The difference between the doses for different anode/filter combinations increased with the phantom thickness. For a 5-cm phantom, with a peak tube voltage of 27 kV and a SDNR of 5, the mean glandular dose associated with the use of W/Rh was reduced by 49% when compared to the molybdenum/molybdenum (Mo/Mo) anode/filter combination and by 33% when compared to Mo/Rh. Based on these measurements, the use of the W/Rh anode/filter can be recommended. It remains important, however, to select the appropriate dose level. PMID- 17268799 TI - Imaging the cranial nerves: part II: primary and secondary neoplastic conditions and neurovascular conflicts. AB - There have been unprecedented improvements in cross-sectional imaging in the last decades. The emergence of volumetric CT, higher field MR scanners and higher resolution MR sequences is largely responsible for the increasing diagnostic yield of imaging in patients presenting with cranial nerve deficits. The introduction of parallel MR imaging in combination with small surface coils allows the depiction of submillimetric nerves and nerve branches, and volumetric CT and MR imaging is able to provide high quality multiplanar and curved reconstructions that can follow the often complex course of cranial nerves. Seeking the cause of a cranial nerve deficit is a common indication for imaging, and it is not uncommon that radiologists are the first specialists to see a patient with a cranial neuropathy. To increase the diagnostic yield of imaging, high-resolution studies with smaller fields of view are required. To keep imaging studies within a reasonable time frame, it is mandatory to tailor the study according to neuro-topographic testing. This review article focuses on the contribution of current imaging techniques in the depiction of primary and secondary neoplastic conditions affecting the cranial nerves as well as on neurovascular conflicts, an increasingly recognized cause of cranial neuralgias. PMID- 17268800 TI - Non-cardiac findings on coronary computed tomography and magnetic resonance imaging. AB - Both multislice computed tomography (CT) and magnetic resonance imaging (MRI) are emerging as methods to detect coronary artery stenoses and assess cardiac function and morphology. Non-cardiac structures are also amenable to assessment by these non-invasive tests. We investigated the rate of significant and insignificant non-cardiac findings using CT and MRI. A total of 108 consecutive patients suspected of having coronary artery disease and without contraindications to CT and MRI were included in this study. Significant non cardiac findings were defined as findings that required additional clinical or radiological follow-up. CT and MR images were read independently in a blinded fashion. CT yielded five significant non-cardiac findings in five patients (5%). These included a pulmonary embolism, large pleural effusions, sarcoid, a large hiatal hernia, and a pulmonary nodule (>1.0 cm). Two of these significant non cardiac findings were also seen on MRI (pleural effusions and sarcoid, 2%). Insignificant non-cardiac findings were more frequent than significant findings on both CT (n = 11, 10%) and MRI (n = 7, 6%). Incidental non-cardiac findings on CT and MRI of the coronary arteries are common, which is why images should be analyzed by radiologists to ensure that important findings are not missed and unnecessary follow-up examinations are avoided. PMID- 17268801 TI - Late-phase MSCT in the different stages of myocardial infarction: animal experiments. AB - The purpose of this study was to intraindividually evaluate myocardial late enhancement on multislice spiral computed tomography (MSCT) for the assessment of the different stages of myocardial infarction (MI) in comparison with magnetic resonance (MR) imaging. Reperfused MI was successfully induced in seven pigs. Delayed enhancement MR imaging and late-phase MSCT were performed on day 0 as well as 7, 28 and 90 days after the procedure. The pigs were sacrificed, and 2,3,5-triphenyltetrazolin-chloride (TTC) staining was acquired. MI size was compared between the different imaging techniques and over time applying Bland Altman plots and multivariate analysis with repeated measures. On day 0 the mean MI size was 23.7 +/- 11.8% of the left ventricular area on MSCT and 24.5 +/- 10.6% on MR imaging. On day 90 infarct sizes decreased significantly to 16.9 +/- 8.4% and 18.9 +/- 8.0%, respectively (P = 0.0019). On TTC staining the size of MI was 16.8 +/- 8.2%. Bland-Altman plots showed a good agreement between MSCT and MR imaging with mean deviations ranging from -3.4% to -1.9%. No significant difference between MSCT and MR imaging was found. Myocardial late enhancement on MSCT correlates well with delayed enhancement MR imaging during the different stages of MI and allows for reliable assessment of reperfused MI during acute, subacute and chronic stages. PMID- 17268802 TI - Evaluation of the influence of acquisition and reconstruction parameters for 16 row multidetector CT on coronary calcium scoring using a stationary and dynamic cardiac phantom. AB - A calcium-scoring phantom with hydroxyapatite-filled cylindrical holes (0.5 to 4 mm) was used. High-resolution scans were performed for an accuracy baseline. The phantom was mounted to a moving heart phantom. Non-moving data with the implementation of an ECG-signal were acquired for different pitches (0.2/0.3), heart rates (60/80/95 bpm) and collimations (16 x 0.75/16 x 1.5 mm). Images were reconstructed with a cone-beam multi-cycle algorithm at a standard thickness/increment of 3 mm/1.5 mm and the thinnest possible thickness (0.8/0.4 and 2/1). Subsequently, ECG-gated moving calcium-scoring phantom data were acquired. The calcium volume and Agatston score were measured. The temporal resolution and reconstruction cycles were calculated. High-resolution scans determine the calcium volume with a high accuracy (mean overestimation, 0.8%). In the non-moving measurements, the volume underestimation ranged from about 6% (16 x 0.75 mm; 0.8/0.4 mm) to nearly 25% (16 x 1.5 mm; 3/1.5 mm). Moving scans showed increased measurement errors depending on the reconstructed RR interval, collimation, pitch, heart rate and gantry rotation time. Also, a correlation with the temporal resolution could be found. The reliability of calcium-scoring results can be improved with the use of a narrower collimation, a lower pitch and the reconstruction of thinner images, resulting in higher patient doses. The choice of the correct cardiac phase within the RR interval is essential to minimize measurement errors. PMID- 17268803 TI - Enhanced tolerance to oxidative stress in transgenic tobacco plants expressing three antioxidant enzymes in chloroplasts. AB - The effect of simultaneous expression of genes encoding three antioxidant enzymes, copper zinc superoxide dismutase (CuZnSOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), and dehydroascorbate (DHA) reductase (DHAR, EC 1.8.5.1), in the chloroplasts of tobacco plants was investigated under oxidative stress conditions. In previous studies, transgenic tobacco plants expressing both CuZnSOD and APX in chloroplast (CA plants), or DHAR in chloroplast showed enhanced tolerance to oxidative stresses, such as paraquat and salt. In this study, in order to develop transgenic plants that were more resistant to oxidative stress, we introduced the gene encoding DHAR into CA transgenic plants. Mature leaves of transgenic plants expressing all three antioxidant genes (CAD plants) had approximately 1.6-2.1 times higher DHAR activity, and higher ratios of reduced ascorbate (AsA) to DHA, and oxidized glutathione (GSSG) to reduced glutathione (GSH) compared to CA plants. CAD plants were more resistant to paraquat-induced stress, exhibiting only 18.1% reduction in membrane damage relative to CA plants. In addition, seedlings of CAD plants had enhanced tolerance to NaCI (100 mM) compared to CA plants. These results indicate that the simultaneous expression of multiple antioxidant enzymes, such as CuZnSOD, APX, and DHAR, in chloroplasts is more effective than single or double expression for developing transgenic plants with enhanced tolerance to multiple environmental stresses. PMID- 17268804 TI - Modeling initial contact dynamics during ambulation with dynamic simulation. AB - Ankle-foot orthoses are frequently used interventions to correct pathological gait. Their effects on the kinematics and kinetics of the proximal joints are of great interest when prescribing ankle-foot orthoses to specific patient groups. Mathematical Dynamic Model (MADYMO) is developed to simulate motor vehicle crash situations and analyze tissue injuries of the occupants based multibody dynamic theories. Joint kinetics output from an inverse model were perturbed and input to the forward model to examine the effects of changes in the internal sagittal ankle moment on knee and hip kinematics following heel strike. Increasing the internal ankle moment (augmentation, equivalent to gastroc-soleus contraction) produced less pronounced changes in kinematic results at the hip, knee and ankle than decreasing the moment (attenuation, equivalent to gastroc-soleus relaxation). Altering the internal ankle moment produced two distinctly different kinematic curve morphologies at the hip. Decreased internal ankle moments increased hip flexion, peaking at roughly 8% of the gait cycle. Increasing internal ankle moments decreased hip flexion to a lesser degree, and approached normal at the same point in the gait cycle. Increasing the internal ankle moment produced relatively small, well-behaved extension-biased kinematic results at the knee. Decreasing the internal ankle moment produced more substantial changes in knee kinematics towards flexion that increased with perturbation magnitude. Curve morphologies were similar to those at the hip. Immediately following heel strike, kinematic results at the ankle showed movement in the direction of the internal moment perturbation. Increased internal moments resulted in kinematic patterns that rapidly approach normal after initial differences. When the internal ankle moment was decreased, differences from normal were much greater and did not rapidly decrease. This study shows that MADYMO can be successfully applied to accomplish forward dynamic simulations, given kinetic inputs. Future applications include predicting muscle forces and decomposing external kinetics. PMID- 17268805 TI - Thermally induced and developmentally regulated expression of a small heat shock protein in Trichinella spiralis. AB - A cDNA encoding a small heat shock protein of Trichinella spiralis, Ts-sHsp, was cloned and expressed and is herein characterized. This cDNA encoded a predicted protein of 165 amino acids, which had a high sequence identity in alpha crystallin domain with various small heat shock proteins of other organisms. A Western blot analysis indicated that anti-Ts-sHsp recombinant antibody recognized the protein of adults and larvae migrating at about 19 kDa. An in situ localization study showed the protein to be abundantly present in the body wall muscle cells, hypodermis, stichocytes, and esophagus of muscle larvae. The Ts sHsp recombinant protein possessed chaperone activity to suppress the thermally induced aggregation of citrate synthase. This sHsp was expressed at various developmental stages of T. spiralis, but at different levels. A high level was observed in mature muscle larvae (infective larvae), which was much higher than the levels seen in adults, newborn larvae, or immature muscle larvae. The expression of the sHsp gene was thermal inducible, thus responding to both cold (0 degrees C) and heat shock (43 degrees C) stress; however, at different patterns. The expression of Ts-sHsp increased gradually from 3 to 72 h after cold stress, while the expression was elevated to its highest after 3 h heat stress and then decreased. These results suggest that this small heat shock protein likely plays a role in the tolerance to both chemical and physical stresses, thereby enhancing the survival ability of Trichinella muscle larvae. PMID- 17268806 TI - Epidemiology of hookworm (Uncinaria spp.) infection in New Zealand (Hooker's) sea lion (Phocarctos hookeri) pups on Enderby Island, Auckland Islands (New Zealand) during the breeding seasons from 1999/2000 to 2004/2005. AB - This is the first investigation of the epidemiology of hookworm (Uncinaria spp.) infection in New Zealand sea lions (NZSLs; Phocarctos hookeri) on Enderby Island, Auckland Islands. The examination of faeces for hookworm eggs in various age categories of sea lions revealed that only pups up to at least 3 months of age harboured adult hookworms in their intestines. Gross necropsy of more than 400 pups from 1999/2000 to 2004/2005 showed that the prevalence of hookworm infection varied significantly between years and was higher from mid-January to the end of February when the majority of pups were between 3 and 9 weeks old. The average burden of adult parasites per pup was not influenced by the host's sex and body condition or by year. This study also provided evidence for transmission occurring by the transmammary route in NZSLs. PMID- 17268807 TI - Comparison of a novel semi-nested polymerase chain reaction (PCR) with a uniplex PCR for the detection of Acanthamoeba genome in corneal scrapings. AB - A semi-nested polymerase chain reaction (snPCR) was developed to improve the sensitivity of detection of Acanthamoeba sp. genome from corneal scrapings of Acanthamoeba keratitis patients. The snPCR was developed using a laboratory designed inner forward primer targeting the 450-bp product of the 18s rRNA-gene based PCR. The snPCR was optimized using 11 Acanthamoeba sp. culture isolates and further applied onto 35 corneal scrapings from keratitis patients. The sensitivity and specificity of the snPCR was compared against conventional methods (smear and/or culture-gold standard) and the uniplex PCR described by Schroeder et al. Eleven out of the 35 corneal scrapings were positive by the gold standard and snPCR, whereas only 3 of these 11 were positive by the uniplex PCR. The clinical sensitivity and specificity of the snPCR was 100% when compared with the gold standard. DNA sequencing was performed on first round amplicons of four culture isolates and one specimen, and all of them were identified as genus Acanthamoeba when compared with the GenBank database sequences. Application of snPCR on the 11 culture isolates yielded amplicons ranging 120-160 bp in size, indicating sequence variation among the different culture isolates. The clinical sensitivity of snPCR was higher than the conventional methods and the uniplex PCR reported earlier. PMID- 17268809 TI - Study of time-course changes in annual recurrence rates for breast cancer: data analysis of 2,209 patients for 10 years post-surgery. AB - Annual recurrence rates (ARR) are used to assess changes in the risk of breast cancer recurrence following surgery. In this retrospective study, ARR were calculated from the clinical records of 2,209 breast cancer patients who had undergone surgery. The time-course changes of ARR associated with prognostic/predictive factors were calculated. Overall, ARR decreased for 5 years following surgery and then remained almost constant. In hormone receptor (HR) negative patients, ARR peaked after 2 years and peaked again at 6-7 years. In HR positive patients, ARR peaked at 2 years. ARR increased in relation to the number of lymph-node metastases for 5 years, and peaked after 2 years in the absence and presence of venous invasion. The log-rank test demonstrated significant differences in recurrence between HR-negative and HR-positive cancer up to 5 years post-surgery. The presence of venous invasion had a significant effect on recurrence in the first 5 years, and the presence of lymph-node metastasis had a significant effect on recurrence up to and after 5 years. In conclusion, prognostic/predictive factors affected breast cancer recurrence in the first 5 years but had a lesser effect on recurrence more than 5 years post-surgery. PMID- 17268810 TI - The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells. AB - Cell migration is essential in many diverse processes ranging from embryonic development to wound healing and immune response. Cancer cells have recently been shown to utilize chemoattraction mechanisms mediated by chemokines and their respective receptors, e.g., the CXCL12/CXCR4 pathway normally found in leukocytes. Here we show that Slit2, a secreted protein signaling through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, acts as a potent chemoattractant for breast cancer cells. Comparing cell lines specifically metastasizing to either brain or bone, we found significant differences in their responses to CXCL12 and Slit2 treatments, suggesting a role for Slit/Robo signaling in brain metastasis. PMID- 17268811 TI - Quantitative exploration of possible reasons for the recent improvement in breast cancer survival. AB - OBJECTIVE: Breast cancer mortality has been declining in many countries including Canada because of improvements in survival. This study attempts to explain observed trends in breast cancer survival with special attention given to the role of improvements in early detection and treatment. METHODS: This study is based on 4,312 women diagnosed with primary invasive breast carcinoma treated in a Canadian breast center between 1976 and 2000 and followed to the end of 2001. Observed and relative survival rates were calculated. Multivariate relative survival regression models were used to assess trends in breast cancer survival over the study period. RESULTS: The proportion of women with small tumors (< or = 10 mm) was higher in late 1990s, while that of women with regional involvement was lower compared to earlier periods. Adjuvant chemotherapy or endocrine therapy use increased steadily from 6.6% to 84.0% during the study period. Five-year relative survival rates ranged between 82.1% and 83.7% between 1976 and 1990, and increased thereafter to reach 87.6% in 1991-95, and 92.1% in 1996-2000. During the first five years after diagnosis, women diagnosed in 1991-95 and 1996-2000 experienced a reduction in breast cancer mortality of 28% (Relative Risk (RR)= 0.72; 95% CI: 0.59-0.89) and 49% (RR = 0.51; 95% CI: 0.39-0.68) respectively compared to women diagnosed in 1976-90. Improvement in breast cancer survival in 1990's could not be explained by characteristics of women, biology of the tumor, advancements in early detection and type of initial treatments. CONCLUSION: A substantial increase in breast cancer survival was observed in the 1990s but the reasons for this improvement remain elusive. Better knowledge of these reasons could help not only to further reduce the burden related to breast cancer but also the burden related to other major cancer sites. PMID- 17268812 TI - Alcohol metabolism, alcohol intake, and breast cancer risk: a sister-set analysis using the Breast Cancer Family Registry. AB - Moderate alcohol intake has been consistently associated with a modest (30-50%) increase in breast cancer risk, but it remains unclear if certain individuals have higher susceptibility to the harmful effects of alcohol intake. Individuals differ in their ability to metabolize alcohol through genetic differences in alcohol dehydrogenase (ADH), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Using data from the Breast Cancer Family Registry (n = 811 sister sets), we examined whether sisters with breast cancer differ with respect to alcohol consumption and alcohol metabolism (measured by polymorphisms in ADH1B and ADH1C) compared to their sisters without breast cancer. Neither alcohol drinking nor alcohol metabolizing ADH1B and ADH1C genotypes were associated with breast cancer risk. However, only 19% and 42% of sisters were discordant by ADH1B and ADH1C, respectively, and even fewer were discordant by both genotype and alcohol intake, making it difficult to detect differences if they existed. PMID- 17268813 TI - Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women. AB - Life-long exposure to estrogen is an established risk factor for breast cancer development. The underlying mechanism has been suggested to be the binding of estrogen-to-estrogen receptors in mammary tissue, which in turn promotes the proliferation and differentiation of breast tissue. Polymorphisms and haplotypes in estrogen receptor alpha (ESR1) have been reportedly associated with breast cancer risk; however, the results are not fully consistent. In this study, we investigated breast cancer risk associated with genotypes and haplotypes resulting from four ESR1 single nucleotide polymorphisms (SNPs), rs746432, rs2234693, rs9340799, and rs1801132. Genotyping has been performed on 393 breast cancer cases and 790 randomly selected controls in 1,183 Caucasian women over age 65 from the Study of Osteoporotic Fractures (SOF). We observed an allelic protective effect for SNP rs9340799 with an estimated odds ratio (OR) of 0.82 (95% CI = 0.68-1.00; P = 0.04) after adjustment for age, BMI and hip BMD. A protective effect of this SNP has been reported before in several different studies. We did not replicate the previously reported C-C-A-G haplotype association to breast cancer-the C-C-A-G haplotype from these SNPs was rare in this study (estimated frequency below 0.001% in cases and controls). No other statistically significant associations were observed between ESR1 haplotypes from the same four SNPs and the risk of breast cancer in older Caucasian women. PMID- 17268814 TI - Genetic variation in the major mitotic checkpoint genes does not affect familial breast cancer risk. AB - Aneuploidy, an aberrant number of chromosomes, is a very common characteristic of many types of cancers, including tumors of the breast. There is increasing evidence that defects in the spindle assembly checkpoint, which controls correct chromosome segregation between two daughter cells, might contribute to tumorigenesis. In the present study we examined the effect of promoter and coding single nucleotide polymorphisms (SNPs) in six major spindle checkpoint genes (BUB1B, BUB3, CENPE, MAD2L1, MAD2L2, TTK) on familial breast cancer (BC) risk. A case-control study was carried out with a total of nine SNPs using 441 German, familial BC cases and 552 controls matched by age, ethnicity and geographical region. Neither the individual SNPs in the studied genes nor the haplotypes in the BUB1B, CENPE and TTK genes caused any significant effect on the risk of BC. We used the multifactor-dimensionality reduction method in order to identify gene gene interactions among the six mitotic checkpoint genes, but no association was detected. Therefore, our results indicate that the investigated SNPs in the mitotic checkpoint genes do not affect the risk of familial BC. PMID- 17268815 TI - A novel steroidal selective steroid sulfatase inhibitor KW-2581 inhibits sulfated estrogen dependent growth of breast cancer cells in vitro and in animal models. AB - We screened a series of 17beta-(N-alkylcarbamoyl)-estra-1,3,5(10)trine-3-O sulfamate derivatives, and describe here a potent and selective steroid sulfatase (STS) inhibitor with antitumor effects in breast cancer models in vitro and in vivo. In biochemical assays using crude enzymes isolated from recombinant Chinese hamster ovary cells expressing human arylsulfatses (ARSs), one of the best compounds, KW-2581, inhibited STS activity with an IC(50) of 4.0 nM, while > 1000 fold higher concentrations were required to inhibit the other ARSs. The failure to stimulate the growth of MCF-7 human breast cancer cells as well as in uteri in ovariectomized rats indicated the lack of estrogenicity of this compound. In MCF 7 cells transfected with the STS gene, termed MCS-2 cells, KW-2581 inhibited the growth of cells stimulated by estrone sulfate (E1S) but also 5-androstene-3beta, 17beta-diol 3-sulfate (ADIOLS) and dehydroepiandrostenedione 3-sulfate. We found that oral administration of KW-2581 inhibited both E1S- and ADIOLS-stimulated growth of MCS-2 cells in a mouse hollow fiber model. In a nitrosomethylurea induced rat mammary tumor model, KW-2581 induced regression of E1S-stimulated tumor growth as effectively as tamoxifen or another STS inhibitor, 667 Coumate. Dose-response studies in the same rat model demonstrated that more than 90% inhibition of STS activity in tumors was necessary to induce tumor shrinkage. STS activity in tumors has well correlated with that in leukocytes, suggesting that STS activity in leukocytes could be used as an easily detectable pharmacodynamic marker. These findings demonstrate that KW-2581 is a candidate for development as a therapeutic agent for the treatment of hormone receptors-positive breast cancer. PMID- 17268816 TI - A novel dual-target steroid sulfatase inhibitor and antiestrogen: SR 16157, a promising agent for the therapy of breast cancer. AB - Endocrine therapy is the ideal treatment choice for estrogen receptor alpha (ERalpha)-positive breast cancer patients. Principal used therapies target either the ERalpha e.g. by selective ERalpha modulators (SERMs) such as tamoxifen or target estrogen biosynthesis with aromatase inhibitors. Steroid sulfatase (STS) plays a crucial role in formation of compounds with estrogenic properties, converting inactive sulfate-conjugated steroids to active non-conjugated forms. Steroid sulfates are considered as a reservoir for active steroids due to their prolonged half-life and increased concentration in plasma. STS is present in several tissues including the breast, and the STS the mRNA level and enzyme activity is significantly increased in ERalpha-positive breast tumors. Inhibition of STS is therefore a new approach for decreasing estrogenic steroids that stimulate breast cancer. The novel dual-acting compound SR 16157 is designed as a sulfamate-containing STS inhibitor that releases a tissue-selective SERM SR 16137. Use of a dual-target STS inhibitor and SERM represents a new strategy in the treatment of hormone-dependent breast cancer. In this study, we tested the potential of SR 16157 and SR 16137 on STS activity, cell growth and ERalpha function in MCF-7 breast cancer cells. We confirmed that the dual-target compound SR 16157 exerts STS inhibition and antiestrogenic effects. SR 16157 was a highly effective growth inhibitor, being 10 times more potent than the antiestrogens SR 16137 and tamoxifen. Relative to tamoxifen, SR 16137 displays profoundly improved ERalpha binding affinity and antiestrogenic effects on expression of estrogen regulated genes. Thus, the dual-target SR 16157 is possibly a promising new treatment alternative, superior to tamoxifen. PMID- 17268817 TI - Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/"triple-negative" breast cancer cell lines growing in vitro. AB - Dasatinib is an orally active small molecule kinase inhibitor of both the src and abl proteins. To evaluate the potential role of dasatinib in breast cancer we used 39 human breast cancer cell lines that have been molecular profiled using Agilent Microarrays. They represent both luminal and basal breast cancer subtypes based on the relative gene expression of cytokeratin (CK) 8/CK18 and CK5/CK17, respectively, and those that have undergone an epithelial-to-mesenchymal transition (post-EMT) based on their expression of vimentin and the loss of CKs. When treated with 1 mICROM dasatinib in vitro 8 of them were highly sensitive (>60% growth inhibition), 10 of them were moderately sensitive (40-59% growth inhibition), and 21 were resistant to dasatinib. A highly significant relationship between breast cancer subtype and sensitivity to dasatinib was observed (chi2 = 9.66 and P = 0.008). Specifically, basal-type and post-EMT breast cancer cell lines were most sensitive to growth inhibition by dasatinib. In an attempt to identify potential predictive markers of dasatinib response other than breast cancer subtype we analyzed the baseline gene expression profiles for differentially expressed genes. We identified a set of three biologically relevant genes whose elevated expression is associated with dasatinib inhibition including moesin, caveolin-1, and yes-associated protein-1 with a sensitivity and specificity of 88 and 86%, respectively. Importantly, these data provide scientific rationale for the clinical development of dasatinib in the treatment of women with "triple-negative" breast cancer, a subtype that is categorized as being aggressive and lacking effective treatments (i.e. hormonal manipulation or trastuzumab). PMID- 17268818 TI - Clinical and pathological correlations in male breast cancer: intratumoral aromatase expression via tissue microarray. AB - BACKGROUND: Male breast cancer (MBC) commonly expresses hormone receptors and there is anecdotal evidence of disease responsivity to aromatase inhibitors in the metastatic setting. Our objectives were to: (i) assess clinical-pathologic characteristics in a consecutive cohort of MBC (ii) evaluate intratumoral aromatase (ITA) expression via tissue microarray (TMA) and (iii) assess the prognostic impact of ITA METHODS: A retrospective review was conducted to identify all cases of MBC seen at the Nova Scotia Cancer Center between 1985 and 2005. Specimens were reviewed for standard pathologic characteristics and tumor blocks were incorporated into three TMA's (four 1 mm cores per tumor). Immunohistochemistry (IHC) for ER, PR, Her2-neu and ITA was performed blinded to clinical outcomes. ITA staining intensity was compared to control, benign hepatic tissue and if greater than or equal to liver was scored positive and if less than liver was scored negative. The log-rank test was used for survival comparisons and Kaplan-Meyer curves were used to estimate 3- and 5-year progression-free and overall survival probabilities. RESULTS: Fifty-four cases were identified with a median age of 64 (31-85 years). Median tumor size was 2.6 cm (0.3-8.0 cm) and 22(41%) had nodal metastases. Forty-five cases had tissue available for IHC. Of these, 40 (89%) were ER and 33 (73%) were PR positive. Her2-neu was overexpressed in four cases (10%) and 12 (27%) were positive for ITA expression. ITA positive tumors were less likely to be grade 3, have lymphovascular invasion or nodal metastases and were more likely to be of favorable histology compared to ITA negative tumors. In univariate analysis strong (versus weak) ITA expression was associated with improved 5 year overall (92% vs. 49%, P = 0.038) but not progression-free (82% vs. 76% P = 0.44) survival rates. CONCLUSIONS: Tumors with strong ITA expression may have a less aggressive phenotype compared to those with negative/weak ITA expression. Further investigation of ITA as a relevant prognostic factor as well as a potential therapeutic target in MBC is warranted. PMID- 17268819 TI - Serial 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to monitor treatment of bone-dominant metastatic breast cancer predicts time to progression (TTP). AB - BACKGROUND: The response of bone-dominant (BD) breast cancer to therapy is difficult to assess by conventional imaging. Our preliminary studies have shown that quantitative serial 2-[(18)F] fluoro-2-deoxy-D: -glucose positron emission tomography (FDG PET) correlates with therapeutic response of BD breast cancer, but the relationship to long-term outcome measures is unknown. Our goal was to evaluate the prognostic power of serial FDG PET in BD breast cancer patients undergoing treatment. METHODS: We reviewed medical records of 405 consecutive breast cancer patients referred for FDG PET. Of these, 28 demonstrated metastatic BD breast cancer, were undergoing treatment, had at least 2 serial PET scans, and had abnormal FDG uptake on the first scan. Standardized uptake value (SUV) for the most conspicuous bone lesion at the initial scan, absolute change in SUV over an interval of 1-17 months, and percent change in SUV were considered as predictors of time-to-progression (TTP) and time to skeletal-related event (t SRE). RESULTS: Using proportional hazards regression, smaller percentage decreases in SUV (or increases in SUV) were associated with a shorter TTP (P < 0.006). A patient with no change in SUV was twice as likely to progress compared to a patient with a 42% median decrease in SUV. A higher SUV on the initial FDG PET predicted a shorter t-SRE (hazard ratio = 1.30, P < 0.02). CONCLUSIONS: Changes in serial FDG PET may predict TTP in BD metastatic breast cancer patients. However, larger prospective trials are needed to validate changes in FDG PET as a surrogate endpoint for treatment response. PMID- 17268820 TI - Hepatic copper-transporting ATPase ATP7B: function and inactivation at the molecular and cellular level. AB - Copper-transporting ATPase ATP7B (Wilson disease protein) is a member of the P type ATPase family with characteristic domain structure and distinct ATP-binding site. ATP7B plays a central role in the regulation of copper homeostasis in the liver by delivering copper to the secretory pathway and mediating export of excess copper into the bile. The dual function of ATP7B in hepatocytes is coupled with copper-dependent intracellular relocalization of the transporter. The final destination of ATP7B in hepatocytes during the copper-induced trafficking process is still under debate. We show the results of immunocytochemistry experiments in polarized HepG2 cells that support the model in which elevated copper induces trafficking of ATP7B to sub-apical vesicles, and transiently to the canalicular membrane. In Atp7b-/- mice, an animal model of Wilson disease, both copper delivery to the trans-Golgi network and copper export into the bile are disrupted despite large accumulation of copper in the cytosol. We review the biochemical and physiological changes associated with Atp7b inactivation in mouse liver and discuss the pleiotropic consequences of the common Wilson disease mutation, His1069Gln. PMID- 17268821 TI - Heme acquisition by hemophores. AB - Bacterial hemophores are secreted to the extracellular medium, where they scavenge heme from various hemoproteins due to their higher affinity for this compound, and return it to their specific outer membrane receptor. HasR, the outer membrane receptor of the HasA hemophore, assumes multiple functions which require various energy levels. Binding of heme and, of heme-free or heme-loaded hemophores is energy-independent. Heme transfer from the holo-hemophore to the outer membrane receptor is also energy-independent. In contrast, heme transport and hemophore release require basal or high levels of TonB and proton motive force, respectively. In addition, HasR is a component of a signaling cascade, regulating expression of the has operon via specific sigma and anti-sigma factors encoded by genes clustered at the has operon. The signal is the heme landing on HasR in the presence of the hemophore in its apo form. The has system is the only system thus far characterized in which the anti-sigma factor is submitted to the same signaling cascade as the target operon. Specific autoregulation of the has system, combined with negative regulation by the Fur protein, permits bacterial adaptation to the available iron source. In the presence of a heme-loaded hemophore, inactive anti-sigma factor is accumulated and can be activated as soon as the heme source dries up. Hence, the has system, instead of being submitted to amplification like other systems regulated by sigma anti-sigma factors, functions by pulses triggered by heme availability. PMID- 17268822 TI - An isorhamnetin rhamnoglycoside serves as a costimulant for sugars and amino acids in feeding responses of adult western corn rootworms (Diabrotica virgifera virgifera) to corn (Zea mays) pollen. AB - Adult beetles of Diabrotica virgifera virgifera LeConte (western corn rootworm) feed on pollen of Zea mays L. (corn) and other plant species. To identify D. virgifera feeding stimulants, beetle responses to mixtures of known and novel phagostimulants, presented at their naturally occurring concentrations in maize pollen, were compared to individual component responses applying the amount occurring in 0.2 mg of pollen per cellulose feeding disk. On a molar basis, three major sugars (fructose, glucose, and sucrose) were more prevalent in corn pollen buffer extract (CPE) than free amino acids. Western corn rootworm feeding was stimulated by the three sugars (28% disk consumption) and, to an even greater extent, by a mixture of 21 free amino acids (41% disk consumption). However, the combination of three sugars and 21 amino acids elicited a level of D. virgifera feeding (41% disk consumption) similar to that of the 21 amino acids alone. A novel maize pollen phagostimulant was purified from CPE by using solid-phase extraction followed by RP-HPLC. Based on its mass fragment pattern, two UV maxima (254 and 359 nm), and previous isolation from maize pollen, this phagostimulant is tentatively identified as isorhamnetin 3-O-neohesperidoside. This compound interacted additively with the mixture of three sugars and 21 amino acids, to produce 77% of the phagostimulation level of CPE. Therefore, a possible stimulatory mechanism for D. virgifera feeding on corn pollen has been elucidated. PMID- 17268823 TI - Characterization and comparison of major urinary proteins from the house mouse, Mus musculus domesticus, and the aboriginal mouse, Mus macedonicus. AB - Urine from the house mouse, Mus musculus domesticus, contains a high concentration of major urinary proteins (MUPs), which convey olfactory information between conspecifics. In wild populations, each individual expresses a different pattern of around 8 to 14 electrophoretically separable MUP isoforms. To examine whether other Mus species express MUPs and exhibit a similar level of individual heterogeneity, we characterized urinary proteins in urine samples from an aboriginal species, Mus macedonicus, captured from different sites in Turkey. Anion exchange chromatography and electrospray ionization mass spectrometry demonstrated that M. macedonicus urine contained a single major peak of mass 18,742 Da, and in contrast to M. m. domesticus, all individuals were the same. The M. macedonicus masses were not predicted from any known MUP gene sequence. Endoproteinase Lys-C (Lys-C) digestion of the purified M. macedonicus urinary protein followed by matrix assisted laser desorption time of flight (MALDI-TOF) mass spectrometry demonstrated that it shared considerable, but not complete, sequence homogeneity with M. m. domesticus MUPs. Three M. macedonicus Lys-C peptides differed in mass from their M. m. domesticus counterparts. These three peptides were further characterized by tandem mass spectrometry. The complete sequences of two were determined, and in conjunction with methyl esterification, the amino acid composition of the third was inferred, and the sequence narrowed down to three permutations. The complete M. macedonicus sequence contained a maximum of seven amino acid substitutions, discernible by tandem mass spectrometry, relative to a reference M. m. domesticus sequence. Six of these were on the surface of the molecule. Molecular modeling of the M. macedonicus sequence demonstrated that the amino acid substitutions had little effect on the tertiary structure. The differences in the level of heterogeneity between the two species are discussed in relation to their environment and behavior. In addition, the differences in protein structure allow speculation into molecular mechanisms of MUP function. PMID- 17268824 TI - Assessment and implications of intraspecific and phenological variability in monoterpenes of Scots pine (Pinus sylvestris) foliage. AB - Scots pine populations contain individuals with widely differing amounts and composition of monoterpenes and exist as one of two chemotypes: with or without delta3-carene. We investigated the significance for ecological studies of two types of variation in monoterpenes: (1) the inherent variability in the concentration of monoterpenes or their relative amounts in needles of seedlings, saplings, and mature trees; and (2) phenological variation in developing needles. The relative composition of needle monoterpenes in 5-year-old saplings changed during the needle development period until the final composition was reached upon needle maturity. Changes in composition depended on chemotype. Needles of the "no delta3-carene" chemotype had higher absolute concentrations of alpha-pinene, beta pinene, camphene, and total monoterpenes than "delta3-carene" chemotype. For the "delta3-carene" chemotype, the relative concentration of delta3-carene during the needle growing season and immediately after emergence of seedlings was higher compared to that reached at needle maturity. Repeated removal of single needles (at weekly intervals during growth) from 5-year-old saplings did not influence the composition of monoterpenes. Within a natural Scots pine dominated woodland, 18% of mature Scots pines (N=574) belonged to the "no-delta3-carene" chemotype. Chemotypic variation within populations means that the statistical power with which differences in monoterpene concentrations can be detected is lower when sampling from the whole population compared to sampling within chemotypes. Reduction of this background variation and accounting for chiral variation if present, would significantly aid efficiency, interpretation, and understanding of processes in chemical and ecological research. One method for achieving this is the screening of plants for chemotypes before the establishment of experiments or field sampling regimes. We present a summary of suitable analytical methods for needle tissue that facilitates this prior screening. PMID- 17268825 TI - Temperature as a modifier of plant-herbivore interaction. AB - Temperature directly affects the growth, survival, and development rates of poikilothermic insect herbivores; it may also have an important indirect impact, via the activities of plant defensive enzymes. The effects of wounding birch leaves and temperature on the growth and development rates of a Lepidopteran moth, Epirrita autumnata, were studied. We also examined the activities of a mountain birch (Betula pubescesns spp. czerepanovii) defensive enzymes, specifically the polyphenoloxidases (PPOs), in relation to temperature and wounding. The optimal temperature for early instars in terms of survival and developmental rates was between +15 and 20 degrees C. Wounding treatment had different effects on birch PPO activity depending on the temperature: at +12 degrees C, wounding decreased the activity, suggesting induced amelioration at that temperature, whereas at +25 degrees C, wounding increased the activity, suggesting induced resistance. However, larval growth was retarded slightly, but significantly, on the leaves of wounded twigs at both temperatures. Both PPO activity and larval growth rates were affected within 12 h, indicating the existence of a transcription- and translation-independent defense system in birch leaves. We suggest that underlying the increase in PPO activity and the decrease in larval growth rate may be H2O2, which has been shown to accumulate in response to wounding. Our results also provide a possible biological mechanism for the hypothesis that low temperatures promote the success of E. autumnata and other Lepidopteran larvae via decreased defensive enzyme activities of host plants at lower temperatures. PMID- 17268826 TI - The impact of state laws protecting abortion clinics and reproductive rights on crimes against abortion providers: deterrence, backlash, or neither? AB - Since Roe v. Wade, most states have passed laws either restricting or further protecting reproductive rights. During a wave of anti-abortion violence in the early 1990s, several states also enacted legislation protecting abortion clinics, staff, and patients. One hypothesis drawn from the theoretical literature predicts that these laws provide a deterrent effect and thus fewer anti-abortion crimes in states that protect clinics and reproductive rights. An alternative hypothesis drawn from the literature expects a backlash effect from radical members of the movement and thus more crimes in states with protective legislation. We tested these competing hypotheses by taking advantage of unique data sets that gauge the strength of laws protecting clinics and reproductive rights and that provide self-report victimization data from clinics. Employing logistic regression and controlling for several potential covariates, we found null effects and thus no support for either hypothesis. The null findings were consistent across a number of different types of victimization. Our discussion contextualizes these results in terms of previous research on crimes against abortion providers, discusses alternative explanations for the null findings, and considers the implications for future policy development and research. PMID- 17268827 TI - Transgression wrongfulness outweighs its harmfulness as a determinant of sentence severity. AB - When students suggest sentences for criminal offenders, do they rely more heavily on the harmfulness or on the wrongfulness of the offender's conduct? In Study 1, 116 Princeton University undergraduates rated the harmfulness and wrongfulness of, and suggested appropriate sentences for, a series of crimes. As expected, participants emphasized wrongfulness when choosing an appropriate criminal punishment. In Study 2, 33 Princeton undergraduates made similar ratings for violations of the University Honor Code, and rated their contempt for fabricated amendments to the Code that required sentencers to focus either only on harmfulness or only on wrongfulness. Again, sentences more closely reflected wrongfulness ratings, and participants were more contemptuous of the harmfulness based proposal. We also consider the theoretical and practical implications of these findings for sentencing laws and policy. PMID- 17268828 TI - Endometrioma of the large bowel. PMID- 17268829 TI - Ulcerative jejunoileitis: a complication of celiac sprue simulating Crohn's disease diagnosed with capsule endoscopy (PillCam). PMID- 17268830 TI - Growth rate of locally recurrent hepatocellular carcinoma after transcatheter arterial chemoembolization: comparing the growth rate of locally recurrent tumor with that of primary hepatocellular carcinoma. AB - We compared the growth rate of locally recurrent hepatocellular carcinoma (HCC) with that of primary HCC. After the first treatment by transcatheter arterial chemoembolization (TACE), 60 locally recurrent HCC nodules were reviewed. The tumor volume doubling time (DT) of locally recurrent HCC was significantly shorter than that of primary HCC. The 95% lower threshold value was 17.7 days. The 6-, 12-, and 36-month recurrence-free rates of the tumors having DTs more than 70 days after the second TACE (77.7%, 53.8%, and 40.4%) were significantly higher than those of the tumors having DTs less than 70 days (26.7%, 26.7%, and 17.8%). Locally recurrent HCCs cannot double in diameter in less than 53 days. In the case that an equivocal lesion smaller than the section collimation depicted during a contrast-enhanced computed tomography (CECT) screening cannot be ruled out as local recurrence, the next CECT screening should be performed 2 months later. PMID- 17268831 TI - Diagnosis of malignant hemangioendothelioma of the small intestine with capsule endoscopy. PMID- 17268832 TI - Intestinal alkaline phosphatase secretion in oil-fed rats. AB - Oil feeding is known to increase the secretion of intestinal alkaline phosphatase (IAP) into serum and this phenomenon is shown to be mediated by surfactant-like particles. These lipoprotein particles are secreted by enterocytes and are rich in phosphatidyl choline and IAP. The exact mechanisms underlying this phenomenon are not known. We studied the effect of feeding different oils varying in fatty acid composition, i.e., coconut oil, corn oil, and cod liver oil, on the secretion of IAP into serum. Also, the effect of actinomycin D treatment on this phenomenon was evaluated. Male albino rats were fed 2 ml of various oils. Alkaline phosphatase activity was measured in serum, luminal washings, and other intestinal fractions. Cod liver oil was found to maximally enhance the soluble and membrane-bound IAP as well as secretion of IAP into lumen and serum. Administration of actinomycin D significantly reduced the enzyme activity in serum and various intestinal fractions in both control and cod liver oil-fed rats. These results were further substantiated by 5-bromo-4-chloroindolyl phosphate staining of IAP in acrylamide gels and by western blotting. The effect of cod liver oil feeding was specific for IAP, as there was no change in the activity of another brush border enzyme, sucrase, under these conditions. These findings suggest that fatty acid composition of the oil determines the amount of IAP secretion and there is coordination between IAP synthesis and its secretion for transport into serum in response to oil feeding. PMID- 17268833 TI - Hepatocellular carcinoma (HCC) with portal vein invasion, masquerading as pancreatic mass, diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). PMID- 17268834 TI - Large cell lymphoma presenting as a flare of colitis in a patient with common variable immune deficiency. PMID- 17268835 TI - Patterns of small intestinal motor activity during intraluminal infusion of elementary diets in dogs. AB - During continuous intraintestinal infusion of elementary diets, periodic fluctuation of the frequency of contractions has been observed. This study sought to characterize the temporospatial organization of this pattern and the influence of cholinergic input. Studies were performed on unanesthetized dogs with a duodenal cannula. Motor activity was recorded by means of infused catheters and external transducers. Nutrients were infused continuously at the duodenum and jejunal levels. Studies were repeated after administration of atropine. Six to 14 periodic variations of frequency of contractions during 10 basal infusion experiments were observed in random order. During duodenal infusion, atropine significantly increased the number of these events, associated with a synchronous pattern. Frequency and amplitude of contractions during jejunal infusion were significantly lower compared to duodenal infusion. Cyclic pattern elicited by nutrient infusion is related to a cholinergic mechanism; changes depend on the level of infusion. PMID- 17268836 TI - Adult intussusception due to enteric neoplasms. PMID- 17268837 TI - Rectal GIST presenting as a submucosal calculus. AB - This case report presents an incidental finding of a rectal GIST (gastrointestinal stromal tumor) presenting as a submucosal calculus, not previously reported. A 53-year-old man without a significant medical history presented with abdominal pain in the left lower quadrant, and with constipation. Upon rectal examination, a hard submucosal swelling was palpated 4 cm from the anus, at 3 o'clock, in the left rectum wall. X-ray photos, computerized tomography (CT)-scan and a magnetic resonance imaging (MRI) scan clearly showed a calculus. Excision revealed a turnip-like lesion, 3.1 x 2.3 x 1.8 cm. Analysis showed it was a rectal GIST, a rare mesenchymal tumor of the gastrointestinal tract, which expressed CD117 (or c-kit, a marker of kit-receptor tyrosine kinase) and CD34. Calcification is not a usual clinicopathological feature of GISTs [1 3], and although a number of rectal GISTs have been reported [4-9], we have found no cases so far of rectal GIST presenting as a submucosal calculus. In general, GISTs are rare mesenchymal tumors of the gastrointestinal tract (nerve tissue, smooth muscle). Histology and immunohistochemistry discriminate gastrointestinal stromal tumors from leiomyomas and neurinomas. The most important location is the stomach; the rectal location is rare. Usually, the classic signs of malignancy such as cellular invasion and metastasis are missing. A set of histologic criteria stratifies GIST for risk of malignant behavior such as mitotic activity and tumor size, cellular pleomorphism, developmental stage of the cell and quantity of cytoplasma [7,13]. Tumors with a high mitotic activity and size above 5 cm are considered malignant. Recent pharmacological advances such as tyrosine kinase inhibitors have determined c-kit (i.e., CD117) as the most important marker, amongst others. C-kit positive tumors respond extremely well to chemotherapy with Imatinib (Glivec, Gleevec) [10-12]. PMID- 17268838 TI - The multiple faces of glucagon-like peptide-1--obesity, appetite, and stress: what is next? A review. AB - By itself, glucagon-like peptide-1(GLP-1) appears to be an excellent drug for appetite control and the treatment of obesity. Unfortunately, few enzymes, such as IV dipeptidyl peptidase and renal excretin, degrade and render GLP-1 inactive within minutes. A receptor agonist, exendin-4, with a longer biological half-life than GLP-1, has been tried. Subcutaneous injection of exendin-4 or continuous IV injection of GLP-1 warrants further research and investigation. PMID- 17268839 TI - Chironomids: suitable test organisms for risk assessment investigations on the potential endocrine disrupting properties of pesticides. AB - Selecting an appropriate invertebrate assay has been a primary goal of national and international testing programs for endocrine disrupting chemicals. The available information on the endocrine system, its hormones and their modes of action in controlling physiological processes in invertebrates is limited and the selection of appropriate test species still presents a challenge. This paper outlines the development of a higher-tier full life cycle (FLC) test for pesticides with the non-biting midge Chironomus riparius (Insecta, Diptera, Chironomidae). As an insect, C. riparius represents the species' richest and ecologically one of the most important groups of invertebrates. In addition, the endocrine system of insects is one of the best studied among the invertebrates. Acute and chronic tests with Chironomus spp. are commonly used for testing and risk assessment of agrochemicals. A chironomid FLC test protocol has been developed and its suitability investigated in an inter-laboratory comparison. The protocol used is based on existing OECD and US-EPA test methods. To verify the suitability of the test to generate endpoints that encompass adverse effects on the arthropod endocrine system, a juvenile hormone analog was selected as positive control substance. Results have demonstrated that the proposed chironomid FLC can be performed in separate laboratories and that the selected arthropod juvenile hormone mimic causes effects. However, the observed toxicity is not proof of an endocrine disruptive mechanism and could equally be evoked by other compounds. Contrary to a screening assay, which aims at revealing a substance's mode-of-action, the FLC test generates robust, population-relevant endpoints that can be used in the risk assessment of agrochemicals. Since the initial results presented in this paper are encouraging we propose to complete the validation of this assay under OECD with high priority. PMID- 17268840 TI - Rotational relaxation of linear pi-systems with flexible side chains in solution. AB - The classical hydrodynamic theory for Brownian rotational motion is applied to model compounds of conjugated polymers with alkoxy side chains of variable length. Theory predicts two rotational relaxation times for these types of molecules with the dipole transition moment parallel to the longest axis whereas experiments reveal only one. The rotational relaxation times and their relative amplitudes were calculated for a wide span of axial ratios of a general ellipsoid. In this way, the range in the axial ratios is obtained such that there is a chance to detect both rates experimentally. Rotational relaxation times of five particular molecules were measured in liquid n-butane. Theoretical calculations using ellipsoid parameters obtained from molecular dynamics calculations compare well with experimental results. Calculation of the rotational relaxation times from the autocorrelation function of the transition dipole moment vector requires significantly greater computational effort. PMID- 17268841 TI - Comparison of LTR enhancer elements in sheep beta retroviruses: insights into the basis for tissue-specific expression. AB - Jaagsiekte sheep retrovirus (JSRV), enzootic nasal tumor virus (ENTV), and endogenous sheep retroviruses (ESRVs) are highly related sheep betaretroviruses that display different expression profiles in vivo. JSRV and ENTV are expressed in lungs and nasal adenocarcinomas, respectively, while ESRVs are primarily expressed in the reproductive tract of ewes. Evidence suggests that the cell tropism of JSRV, ENTV, and ESRVs is due to the transcriptional specificity of the LTRs. We have previously found several enhancer elements in the JSRV LTR that are important for lung-specific expression, including binding sites for the lung specific transcription factor HNF-3beta, as well as binding sites for the ubiquitously expressed transcription factors C/EBP and NF-I. In this study, we have aligned the U3 regions of JSRV, ENTV, and several ESRVs in order to compare the transcriptional enhancer elements of JSRV that are conserved or absent in ESRV and ENTV. All three JSRV U3 sequences examined contain two conserved HNF-3 binding sites, while the ENTV and ESRV U3 regions are not predicted to bind this transcription factor. In addition, the C/EBP binding site is interrupted in the ESRV LTRs, but conserved in the ENTV LTRs. Some enhancer elements are conserved between JSRV and ENTV, but a reporter vector carrying the ENTV-1 LTR showed less activity than a JSRV LTR-driven reporter vector in a lung epithelial cell line. These studies support the importance of LTR enhancer elements in the respective tissue specificities of these exogenous and endogenous betaretroviruses. PMID- 17268842 TI - Effects of typical and atypical antipsychotic drugs on rat brain muscarinic receptors. AB - Quantitative in vitro autoradiography was used to examine changes in muscarinic M1/M4 and M2/M4 receptors (targeted with [3H]pirenzepine and [3H]AF-DX384 respectively), in rats treated with the typical (haloperidol) and atypical (clozapine and olanzapine) antipsychotic medications for a period of 36 days. Rats were sacrificed at either 2 h or 48 h after the last drug administration to examine immediate effects as well as the effects at 48 h after drug withdrawal. Haloperidol significantly increased [3H]pirenzepine binding in the dentate gyrus (37%) and in the CA1 region of the hippocampus (34%) in animals sacrificed 2 h after the last drug administration compared to controls. Similarly, clozapine significantly increased [3H]pirenzepine binding in dentate gyrus (29%) in rats sacrificed 2 h after the last drug administration compared to controls. Haloperidol decreased [3H]AF-DX384 binding in the basolateral nucleus of the amygdala (20%) in the rats sacrificed 48 h after the last drug administration compared to controls. These findings suggest that muscarinic receptors and limbic brain regions such as hippocampus and amygdala might represent common targets that mediate beneficial clinical effects of antipsychotic drugs. PMID- 17268843 TI - Fulminant hepatic failure in rats induces oxidative stress differentially in cerebral cortex, cerebellum and pons medulla. AB - Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat braincerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex. PMID- 17268844 TI - Perturbed synaptosomal calcium homeostasis and behavioral deficits following carbofuran exposure: neuroprotection by N-acetylcysteine. AB - The protective effects of N-acetylcysteine (NAC) on carbofuran-induced alterations in calcium homeostasis and neurobehavioral functions were investigated in rats. Rats were exposed to carbofuran at a dose of 1 mg/kg body weight, orally for a period of 28 days. A significant decrease in Ca2+ATPase activity was observed following carbofuran exposure with a concomitant increase in K+ -induced (45)Ca2+ uptake through voltage operated calcium channels. This was accompanied with a marked accumulation of intracellular free calcium in synaptosomes. The increase in intracellular calcium levels were associated with an increased lipid peroxidation and decreased glutathione content in carbofuran exposed animals. NAC administration (200 mg/kg body weight, orally) to the carbofuran exposed animals had a beneficial effect on carbofuran-induced alterations in calcium homeostasis and resulted in repletion in glutathione levels and resulted in lowering the extent of lipid peroxidation. Marked impairment in the motor functions were seen following carbofuran exposure, which were evident by the significant decrease in the locomotor activity and reduction in the retention time of the rats on rotating rods. Cognitive deficits were also seen as indicated by the significant decrease in active and passive avoidance response. NAC treatment, on the other hand, protected the animals against carbofuran-induced neurobehavioral deficits. The results support the hypothesis that carbofuran exerts its toxic effects by disrupting calcium homeostasis, which may have serious consequences on neuronal functioning, and clearly show the potential beneficial effects of N-acetylcysteine on carbofuran induced alterations in synaptosomal calcium homeostasis. PMID- 17268845 TI - Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. AB - Venlafaxine is an approved antidepressant that is an inhibitor of both serotonin and norepinephrine transporters. Medical treatment with oral venlafaxine can be beneficial to depression due to reducing free radical production in the brain and medulla of depression-induced rats because oxidative stress may a play role in some depression. We investigated the effect of venlafaxine administration and experimental depression on lipid peroxidation and antioxidant levels in cortex brain, medulla and erythrocytes of rats. Thirty male wistar rats were used and were randomly divided into three groups. Venlafaxine (20 mg/kg) was orally supplemented to depression-induced rats constituting the first group for four week. Second group was depression-induced group although third group was used as control. Depressions in the first and second groups were induced on day zero of the study by chronic mild stress. Brain, medulla and erythrocytes samples were taken from all animals on day 28. Depression resulted in significant decrease in the glutathione peroxidase (GSH-Px) activity and vitamin C concentrations of cortex brain, glutathione (GSH) value of medulla although their levels were increased by venlafaxine administration to the animals of depression group. The lipid peroxidation levels in the three tissues and nitric oxide value in cortex brain elevated although their levels were decreased by venlafaxine administration. There were no significant changes in cortex brain vitamin A, erythrocytes vitamin C, GSH-Px and GSH, medulla vitamin A, GSH and GSH-Px values. In conclusion, cortex brain within the three tissues was most affected by oxidative stress although there was the beneficial effect of venlafaxine in the brain of depression-induced rats on investigated antioxidant defenses in the rat model. The treatment of depression by venlafaxine may also play a role in preventing oxidative stress. PMID- 17268846 TI - Pyrroloquinoline quinone is a potent neuroprotective nutrient against 6 hydroxydopamine-induced neurotoxicity. AB - Pyrroloquinoline quinone (PQQ), which is an essential nutrient, has been shown to act as an antioxidant. Reactive oxygen species (ROS) are thought to be responsible for neurotoxicity caused by the neurotoxin 6-hydroxydopamine (6 OHDA). In this study, we investigated the ability of PQQ to protect against 6 OHDA-induced neurotoxicity using human neuroblastoma SH-SY5Y. When SH-SY5Y cells were exposed to 6-OHDA in the presence of PQQ, PQQ prevented 6-OHDA-induced cell death and DNA fragmentation. Flow cytometry analysis using the ROS-sensitive fluorescence probe, dihydroethidium, revealed that PQQ reduced elevation of 6 OHDA-induced intracellular ROS. In contrast to PQQ, antioxidant vitamins, ascorbic acid and alpha-tocopherol, had no protective effect. Moreover, we showed that PQQ effectively scavenged superoxide, compared to the antioxidant vitamins. Therefore, our results suggest the protective effect of PQQ on 6-OHDA-induced neurotoxicity is involved, at least in part, in its function as a scavenger of ROS, especially superoxide. PMID- 17268847 TI - Nicotine inhibits bFGF-induced neurite outgrowth through suppression of NO synthesis in H19-7 cells. AB - NO (Nitric oxide) has been known as a biological signaling molecule that can function as a beneficial agent in physiologically essential functions such as differentiation or neurotransmission. In this study, we elucidated how nicotine inhibits neuronal differentiation induced by the basic fibroblast growth factor (bFGF) in hippocampal cell line, H19-7 cells, because nicotine is one of the key neuroregulatory components. Treatment of H19-7 cells with bFGF increased NO production through upregulated iNOS/ nNOS expression, and also increased expressions of neuronal markers such as brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and Neuro-D. Pretreatment of the cells with nicotine decreased iNOS promoter activity as well as iNOS/nNOS expression induced by bFGF, resulting in decreased NO production. Nicotine also suppressed expressions of BDNF, NT3 and Neuro-D, resulting in decreased bFGF-induced neurite outgrowth. These results indicate that nicotine inhibits bFGF-induced neuronal differentiation in H19-7 cells through inhibition of NO formation by suppressing iNOS/nNOS expressions. PMID- 17268848 TI - Ventral tegmental transcriptome response to intermittent nicotine treatment and withdrawal in BALB/cJ, C57BL/6ByJ, and quasi-congenic RQI mice. AB - The aim of this study was to identify neurochemical pathways and candidate genes involved in adaptation to nicotine treatment and withdrawal. Locomotor sensitization was assessed in a nicotine challenge test after exposure to intermittent nicotine treatment and withdrawal. About 24 h after the challenge test the ventral tegmentum of the mesencephaion was dissected and processed using oligonucleotide microarrays with 22,690 probe sets (Affymetrix 430A 2.0). Quasi congenic RQI, and donor BALB/cJ mice developed significant locomotor sensitization, while sensitization was not significant in the background partner, C57BL/6By. Comparing saline treated controls of C57BL/6ByJ and BALB/cJ by a rigorous statistical microarray analysis method we identified 238 differentially expressed transcripts. Quasi-congenic strains B6.Cb4i5-alpha4/Vad and B6.Ib5i7 beta25A/Vad significantly differed from the background strain in 11 and 11 transcripts, respectively. Identification of several cis- and trans-regulated genes indicates that further work with quasi-congenic strains can quickly lead to mapping of Quantitative Trait Loci for nicotine susceptibility because donor chromosome regions have been mapped in quasi-congenic strains. Nicotine treatment significantly altered the abundance of 41, 29, 54, and 14 ventral tegmental transcripts in strains C57BL/6ByJ, BALB/cJ, B6.Cb4i5-alpha4/Vad, and B6.Ib5i7 beta25A/Vad, respectively. Although transcript sets overlapped to some extent, each strain showed a distinct profile of nicotine sensitive genes, indicating genetic effects on nicotine-induced gene expression. Nicotine-responsive genes were related to processes including regulation of signal transduction, intracellular protein transport, proteasomal ubiquitin-dependent protein catabolism, and neuropeptide signaling pathway. Our results suggest that while there are common regulatory mechanisms across inbred strains, even relatively small differences in genetic constitution can significantly affect transcriptome response to nicotine. PMID- 17268849 TI - Down-regulation of platelet-activating factor receptor gene expression during focal reversible cerebral ischemia in rats. AB - Platelet-activating factor (PAF) is an endogenous potent phospholipid mediator in stroke and related to the post-ischemic brain damage. The aim of this study was to investigate the regulation and mechanisms of PAF receptor gene expression in the perifocal regions of cerebral infarction after middle cerebral artery occlusion/reperfusion. Sixty mature Wistar rats were randomly divided into 12 groups: sham-operated control group, simple ischemia 90 min group, 6, 12, 18 h, 1 day (1 d), 2, 3, 4, 5, 6, 7 d reperfusion groups. After the right middle cerebral artery occluded, the rats were suffered from ischemia for 90 min, and then reperfusion was allowed for different time courses. Reverse transcription polymerase chain reaction (RT-PCR) and radioimmunoassay were applied to evaluate the PAF receptor messenger RNA (mRNA) expression and PAF levels in the perifocal regions of cerebral infarction respectively. RT-PCR analysis revealed that PAF receptor mRNA was 0.95 +/- 0.15 in control group. However, following ischemia reperfusion, the levels of PAF receptor mRNA progressively decreased until 2 d of reperfusion (0.54 +/- 0.10), then returned to control group's levels gradually. Compared with the control group's (582 +/- 72 pg/g wet weight), the PAF concentrations of simple ischemic and 6, 12, 18 h, 1, 2 d reperfusion group were significantly higher than that of any other groups. These results indicate that PAF receptor gene expression may be subject to down-regulation in the perifocal regions of cerebral infarction after cerebral ischemia-reperfusion and relative to the increase of endogenous PAF concentrations. PMID- 17268850 TI - Salsolinol, an endogenous neurotoxin, activates JNK and NF-kappaB signaling pathways in human neuroblastoma cells. AB - Salsolinol, an endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson's disease (PD). In the present study, we have investigated the effects of salsolinol on the activation of two different signaling pathways that involve c-Jun N-terminal kinase (JNK), and nuclear factor-kappaB, (NF-kappaB) in human dopaminergic neuroblastoma SH-SY5Y cells. Salsolinol treatment caused upregulation in the levels of c-Jun and phosphorylated c-Jun. It also caused degradation of IkappaBalpha and translocated the active NF-kappaB into the nucleus. The binding activity of NF-kappaB to DNA was enhanced by salsolinol in a concentration dependent manner. Furthermore, salsolinol decreased the levels of the anti-apoptotic protein Bcl-2, and increased pro-apoptotic protein Bax, while enhancing the release of cytochrome-c from mitochondria. Mitochondrial complex-I activity was significantly decreased and reactive oxygen species (ROS) were increased in salsolinol treated cells. These results partly suggest that salsolinol-induced JNK and NF-kappaB signaling pathways may be involved in induction of apoptosis in human dopaminergic neurons, as seen in Parkinson's disease. PMID- 17268851 TI - Tyrosine nitration is a novel post-translational modification occurring on the neural intermediate filament protein peripherin. AB - The biological implication of protein tyrosine nitration in signaling pathways triggered by nitric oxide is recently emerging. Here we report for the first time that nitrotyrosination occurs in the neural intermediate filament protein peripherin. In neuron-like PC12 cells, nitrated peripherin is associated with the cytoskeleton fraction, its level increases during the progression of NGF-induced differentiation and the nitrated protein remains closely associated with stable microtubules. Tyr 17 and Tyr 376 were identified by MALDI-TOF analyses as two specific residues endogenously nitrated. Finally, peripherin nitration is not restricted to PC12 cells but it is also present in vivo in rat brain. PMID- 17268852 TI - Cerebellar granule neurons are more vulnerable to transient transport-mediated glutamate release than to glutamate uptake blockade. correlation with excitatory amino acids levels. AB - The extracellular concentration of glutamate is highly regulated due to its excitotoxic nature. Failure of glutamate uptake or reversed activation of its transporters contributes to neurodegeneration related to some pathological conditions. We have compared the neurotoxicity of the substrate glutamate uptake inhibitor, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), which promotes glutamate release by hetero-exchange, with that of DL-threo-beta-benzyloxyaspartate (DL TBOA), a non-substrate inhibitor, in cerebellar granule cell cultures. PDC substantially increases the extracellular concentration of glutamate during 30 min exposure and causes neuronal death at high concentrations, while DL-TBOA neurotoxicity is only observed after long-term exposure (8-24 h). During mitochondrial inhibition by 3-nitropropionic acid (3-NP), PDC-induced neuronal death is facilitated, but not that of DL-TBOA. In cultures containing a higher population of astrocytes DL-TBOA-induced increase in glutamate levels is more pronounced, but neuronal death is only triggered in the presence of 3-NP. Results suggest that cerebellar granule neurons are more vulnerable to acute transport mediated glutamate release than to uptake blockade, which correlates with the extracellular excitatory amino acids levels. PMID- 17268853 TI - Age-related changes in tau expression in transgenic mouse model of amyotrophic lateral sclerosis. AB - The work is a continuation of studies on tau expression and alternative splicing in the central nervous system of transgenic mice harboring human SOD1 with G93A amyotrophic lateral sclerosis (ALS)-associated mutation. Since age is an important risk factor for ALS, we expanded the studies into younger animals (age 5 and 25 days). We also included cerebellum, a structure not studied in the context of neurodegeneration in ALS. We found decreased total tau-mRNA expression in hippocampus but not in cortex and spinal cord of young transgenics, and a lack of exon 10 in 5-day-old mice. In cerebellum, the total tau-mRNA expression was increased in transgenic animals during the whole period of life, however at the symptomatic stage of ALS (age 120 days) the level of protein was decreased. It can be concluded that the SOD1 G93A mutation causes early alterations of tau expression in cns, which are not exclusively restricted to the upper and lower motor neuron. PMID- 17268854 TI - Differential effects of undernourishment and nutritional rehabilitation on serum leptin levels in male and female rats. AB - Leptin, a peptide hormone, is secreted by adipose tissue and is crucial to the regulation of feeding behaviour. The present study has shown that both male and female rats which have been undernourished since day six of gestation, show significantly decreased serum leptin levels on postnatal day 12; but when undernourishment continues into adulthood, only males continue to show decreased leptin levels. If nutritional rehabilitation is implemented early enough in males, serum leptin levels recover and nearly reach levels found in control adult males. Undernutrition also has a long term effect on body weight in both sexes, but nutritional rehabilitation leads to some degree of body weight recovery varying with sex and the age at which rehabilitation was implemented. Undernutrition seems to affect different developmental processes in males than in females, with males being more vulnerable than females in so far as long-term effects on serum leptin levels. PMID- 17268855 TI - Mechanism of activation of caspase-9 and caspase-3 during hypoxia in the cerebral cortex of newborn piglets: the role of nuclear Ca2+ -influx. AB - In previous studies, we have shown that cerebral hypoxia results in increased activity of caspase-9, the initiator caspase, and caspase-3, the executioner of programmed cell death. We have also shown that cerebral hypoxia results in high affinity Ca2+-ATPase-dependent increase in nuclear Ca2+ -influx in the cerebral cortex of newborn piglets. The present study tests the hypothesis that inhibiting nuclear Ca2+ -influx by pretreatment with clonidine, an inhibitor of high affinity Ca2+ -ATPase, will prevent the hypoxia-induced increase in caspase-9 and caspase-3 activity in the cerebral cortex of newborn piglets. Thirteen newborn piglets were divided into three groups, normoxic (Nx, n=4), hypoxic (Hx, n=4), and hypoxic treated with clonidine (100 mg/kg) (Hx-Cl, n=5). Anesthetized, ventilated animals were exposed to an FiO2 of 0.21 (Nx) or 0.07 (Hx) for 60 min. Cerebral tissue hypoxia was documented biochemically by determining levels of ATP and phosphocreatine (PCr). Caspase-9 and -3 activity were determined spectrofluoro-metrically using specific fluorogenic synthetic substrates. ATP (micromoles/g brain) was 4.6 +/- 0.3 in Nx, 1.7 +/- 0.4 in Hx (P < 0.05 vs. Nx), and 1.5 +/- 0.2 in Hx-Cl (P < 0.05 vs. Nx). PCr (micromoles/g brain) was 3.6 +/- 0.4 in Nx, 1.1 +/- 0.3 in Hx (P < 0.05 vs. Nx), and 1.0 +/- 0.2 in Hx-Cl (P < 0.05 vs. Nx). Caspase-9 activity (nmoles/mg protein/h) was 0.548 +/- 0.0642 in Nx and increased to 0.808 +/- 0.080 (P < 0.05 vs. Nx and Hx-Cl) in the Hx and 0.562 +/- 0.050 in the Hx-Cl group (p = NS vs. Nx). Caspase-3 activity (nmoles/mg protein/h) was 22.0 +/- 1.3 in Nx and 32 +/- 6.3 in Hx (P < 0.05 vs. Nx) and 18.8 +/- 3.2 in the Hx-Cl group (P < 0.05 vs. Hx). The data demonstrate that clonidine administration prior to hypoxia prevents the hypoxia-induced increase in the activity of caspase-9 and caspase-3. We conclude that the high afinity Ca2+ ATPase-dependent increased nuclear Ca2+ during hypoxia results in increased caspase-9 and caspase-3 activity. PMID- 17268856 TI - Long-lasting changes of albino rats behavior and brain bioamines content after immunization against cholecystokinin-3 and -4. AB - Active immunization against cholecystokinin fragments 31-33 (CCK-3) and 30-33 (CCK-4) results in long-lasting changes of albino rats' behavior. CCK-3 and CCK-4 covalently linked to antigen-carrier evokes the suppression of the anxiety, decreases some signs of depression-like behavior and changes the level of bioamines and their catabolites in striatum at least for two months after immunization. These data can provide a perspective approach to the problem of long term correction of behavior. PMID- 17268857 TI - Effects of maintenance electroshock on the oxidative damage parameters in the rat brain. AB - Although several advances have occurred over the past 20 years concerning refining the use and administration of electroconvulsive therapy to minimize side effects of this treatment, little progress has been made in understanding the mechanisms underlying its therapeutic or adverse effects. This work was performed in order to determine the level of oxidative damage at different times after the maintenance electroconvulsive shock (ECS). Male Wistar rats (250-300 g) received a protocol mimicking therapeutic of maintenance or simulated ECS (Sham) and were subsequently sacrificed immediately after, 48 h and 7 days after the last maintenance electroconvulsive shock. We measured oxidative damage parameters (thiobarbituric acid reactive species for lipid peroxidation and protein carbonyls for protein damage, respectively) in hippocampus, cortex, cerebellum and striatum. We demonstrated no alteration in the lipid peroxidation and protein damage in the four structures studied immediately after, 48 h and 7 days after a last maintenance electroconvulsive shock. Our findings, for the first time, demonstrated that after ECS maintenance we did protocol minimal oxidative damage in the brain regions, predominating absence of damage on the findings. PMID- 17268858 TI - Predictors of practitioner self-reported use of evidence-based practices: practitioner training, clinical setting, and attitudes toward research. AB - In light of the recent movement toward evidence-based practice (EBP) in mental health services, practitioner adoption of EBPs in clinical settings has emerged as an important area for study. This paper reports on the results of a national online survey of mental health practitioners in an attempt to identify correlates of self-reported EBP use in practice. The survey consisted of 214 mental health practitioners from 15 states drawn from a diverse set of clinical settings and representing a variety of theoretical orientations. The results indicated that practitioner training (i.e., taking a class in EBPs), the perceived openness of the clinical setting toward EBPs, and the practitioner's attitudes toward treatment research were significant predictors of self-reported EBP use. The relationship between clinical setting and EBP use was partially mediated by attitudes toward treatment research. Negative attitudes toward treatment research partially mediated the relationship between practitioner training and self reported EBP use. The findings are presented within the context of efforts to increase EBP use in clinical settings and implications for clinical training, treatment research, and EBP dissemination efforts are discussed. PMID- 17268859 TI - Conjugation of oligosaccharides by reductive amination to amine modified chondroitin oligomer and gamma-cyclodextrin. AB - Carbohydrates present on cell surfaces participate in numerous biological recognition phenomena including cell-cell interactions, cancer metastasis and pathogen invasion. Therefore, synthetic carbohydrates have a potential to act as pharmaceutical substances for treatment of various pathological phenomena by inhibiting specifically the interaction between cell surface carbohydrates and their protein receptors (lectins). However, the inherently low affinity of carbohydrate-protein interactions has often been an obstacle for successful generation of carbohydrate based pharmaceuticals. Multivalent glycoconjugates, i.e. structures carrying several copies of the active carbohydrate sequence in a carrier molecule, have been constructed to overcome this problem. Here we present two novel types of multivalent carbohydrate conjugates based on chondroitin oligomer and cyclodextrin carriers. These carriers were modified to express primary amino groups, and oligosaccharides were then bound to carrier molecules by reductive amination. Multivalent conjugates were produced using the human milk type oligosaccharides LNDFH I (Lewis-b hexasaccharide), LNnT, and GlcNAcbeta1 3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc. PMID- 17268861 TI - Study on poly(vinyl alcohol)/carboxymethyl-chitosan blend film as local drug delivery system. AB - The distinguishable films composed of poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMCS) were prepared by blending/casting method, and loaded with ornidazole (OD) as local drug delivery system. In vitro test, the blend films showed pH-responsive swelling behavior and moderate drug release action, and also exhibited a little antimicrobial activity against E. coli and S. aureus strains. Those characteristics of CMCS/PVA blend films were essentially governed by the weight ratio of CMCS and PVA. Increasing the content of PVA in blend film would decrease swelling and decelerated the drug release. However, increasing the content of CMCS would enhance the antimicrobial activity. The biocompatibility and bioactivity of the blend film were also evaluated using rabbit blood and Wister rats. This blend drug system was of no hemolysis, no toxicity to rat periodontia and no cytotoxicity to the rat muscle. After subcutaneously implanting the blend drug films in Wister rat, the systems kept a good retention at the application site and maintained high drug concentration in long time (5 days) which was longer than the period of drug released in vitro (160 min). PMID- 17268860 TI - Glycotargeting to improve cellular delivery efficiency of nucleic acids. AB - Nucleic acids bearing glycans of various structures have been under vigorous investigation in the past decade. The carbohydrate moieties of such complexes can serve as recognition sites for carbohydrate-binding proteins-lectins-and initiate receptor-mediated endocytosis. Therefore, carbohydrates can enhance cell targeting and internalization of nucleic acids that are associated with them and thus improve the bioavailability of nucleic acids as therapeutic agents. This review summarizes nucleic acid glycosylation in nature and approaches for the preparation of both non-covalently associated and covalently-linked carbohydrate nucleic acid complexes. PMID- 17268862 TI - Repair of experimental Achilles tenotomy with porcine renal capsule material in a rat model. AB - Porcine small intestinal submucosa (SIS) is a collagenous acellular matrix which has found substantial utility as a tissue growth scaffold. In the present study, the utility of porcine renal capsule matrix (RCM) was compared to SIS in a rat Achilles tenotomy repair model. Groups of rats underwent surgical tenotomy followed by either no repair, repair with a SIS graft, or repair with a RCM graft. The weight-bearing ability of the manipulated limb was evaluated for 10 days following surgery using a subjective scale. Tenotomy sites sampled 28 days after surgery were numerically graded for degree of histologic change. There were no statistically significant differences between groups with respect to return to weight-bearing ability (p >or= 0.05) or degree of histologic change (p >or= 0.001); however, a non-significant trend suggested that rats treated with SIS or RCM experienced a faster return to limb function than untreated rats, and RCM treated rats had slightly higher scores for degree of histologic change, suggesting a more rapid repair of the tenotomy site than in SIS-treated or untreated rats. The harvested tenotomy sites in all treatment groups were characterized by marked fibroplasia and presence of macrophages. Remnants of SIS surrounded by macrophages and multi-nucleated giant cells were still present in some rats, however remnants of RCM were not observed, suggesting more rapid incorporation of RCM. The results show that RCM is equivalent to SIS as a material for repair of Achilles tendon injury and merits further study in other tendon injury models. PMID- 17268863 TI - The influence of microstructure on thermal response of glass ionomers. AB - This study was designed to determine the dimensional changes caused by thermal stimuli of glass ionomers with different glass/matrix ratios. Four cylindrical specimens were made for each of four powder/liquid ratios (3:1, 2.5:1, 2:1 and 1.5:1) for a conventional luting glass ionomer, two high viscosity restorative glass ionomers and a restorative resin-modified glass ionomer. The thermal characteristics were determined using a thermal mechanical analyzer (TMA) by heating the samples from 25 degrees C to 70 degrees C at 10 degrees C per minute. All glass ionomers and the resin-modified glass ionomer lost water on heating. The results of the thermal response of these materials were explained in terms of the opposing effects of thermal expansion and desiccation on heating. The contraction on heating of glass ionomer and related materials was found to relate to the glass/matrix ratio but not directly proportional to it. Materials with lower P/L ratios contracted the most when heated to 70 degrees C. The water loss from conventional and resin-modified glass ionomer with different glass/matrix ratios compensated for their thermal expansion and led to a minimal dimensional change when heated up to 50 degrees C. This outcome may be interpreted as an example of smart behaviour of these materials. PMID- 17268864 TI - Scanning electron microscopy and energy-dispersive X-ray analysis of self-etching adhesive systems to ground and unground enamel. AB - The morphological analysis of the ground and unground enamel was treated with three different self-etching adhesive systems. Ultrastructural features were observed by using the field emission scanning electron microscope (FESEM) in combination with Energy Dispersive X-Ray Spectroscopy (EDS) analysis. Thirty extracted human molars were used for this study. Teeth were divided into two groups. In the first group unground enamel was etched with either Clearfil SE Bond (Kuraray-Japan), G Bond (GC-Japan) or Tri S Bond (Kuraray-Japan) according to the manufactures instructions. In the second group ground enamel was treated as above. In addition 24 ungrounded and grounded enamel specimens were etched and bonded with the three self-etching adhesives and restored with composite resin (Clearfil ST-Kuraray). Then they were cross-sectioned and interfacial analysis was done with the combination of EDS analysis. Etching patterns of the enamel varied according to the self-etching adhesive. Clearfil SE Bond produced micro irregular etching pattern creating crater like area in ground enamel while other two produced mild etching pattern. All three adhesives produced incomplete etching on unground enamel. Interfacial studies showed demineralization for the bonding agent penetration and the formation of hybrid layer. The self-etching adhesives produced different specific SEM morphologies on unground and ground enamel. PMID- 17268865 TI - Preparation of bioactive flexible poly(tetramethylene oxide) (PTMO)-CaO-Ta2O5 hybrids. AB - Poly(tetramethylene oxide) (PTMO)-CaO-Ta2O5 hybrids were prepared by hydrolysis and polycondensation of triethoxysilane-functionalized PTMO (Si-PTMO), tantalum ethoxide (Ta(OEt)5) and CaCl2. In the system CaO-free PTMO-Ta2O5, Si PTMO/Ta(OEt)5 weight ratios were 30/70, 40/60 and 50/50 (hybrids PT30Ca0, PT40Ca0 and PT50Ca0, respectively). In the system PTMO-CaO-Ta2O5, the Si-PTMO/Ta(OEt)5 weight ratio was 40/60 and CaCl2/Ta(OEt)5 mole ratios were 0.05, 0.10 and 0.15 (hybrids PT40Ca5, PT40Ca10 and PT40Ca15, respectively). Crack-free transparent monolithic hybrids were obtained for all the examined compositions except for PT30Ca0. Even CaO-free hybrids PT40Ca0 and PT50Ca0 formed apatite on their surfaces in a simulated body fluid (SBF) within 14 days. Hybrid PT40Ca0 showed higher mechanical strength, which was increased by soaking in SBF, and larger strain to failure than human cancellous bone. The CaO-containing hybrids showed higher apatite-forming ability than the CaO-free hybrids, and its apatite-forming ability increased with increasing CaO content. Hybrids PT40Ca10 and PT40Ca15 formed apatite within 3 days. The mechanical strength of PT40Ca15 was, however, lower than PT40Ca0 and was decreased by soaking in SBF. Thus obtained flexible bioactive CaO-free PTMO-Ta2O5 hybrids are expected to be useful as bone substitutes. PMID- 17268866 TI - Characterization of adsorbed silane on fillers used in dental composite restoratives and its effect on composite properties. AB - The purpose was to study the effect of silane treatment of fillers on viscosity, flexural strength, and hydrolytic degradation of experimental dental composite resins fabricated with these fillers. The fillers consisted of a mixture of barium glass and amorphous silica. The resin was mainly based on ethoxylated bisphenol A dimethacrylate and polycarbonate dimethacrylate. The adsorption of silane on the filler surface was characterized by FTIR. There was significant correlation between the adsorbed silane on filler surface and the silane concentration in silane/methanol solution used for filler treatment. The silane concentration varied from 0.75 to 14% by weight. An increase in silane concentration led to a decrease in viscosities of the corresponding composite resins. The flexural strengths of composites with silanated fillers were greater than that of composites with unsilanated fillers: however, no significant difference was found between the flexural strengths of various silanated groups. The resistance to hydrolytic degradation of different composites increased when the fillers were treated with silane and was the highest at 1.1% silane. PMID- 17268867 TI - Staphylococcus aureus adhesion to standard micro-rough and electropolished implant materials. AB - Implant-associated infections can cause serious complications including osteomyelitis and soft tissue damage, and are a great problem due to the emergence of antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In some cases, antibiotic-loaded beads which release the antibiotic locally have been used, however such systems may lead to the development of antibiotic-resistant bacteria, as seen with gentamicin-loaded beads. Hence modifying the actual metal implant surface to inhibit or reduce initial bacterial adhesion may be an alternative option. This study describes the visualisation and quantification of S. aureus adhering to standard micro-rough 'commercially pure' titanium (TS) and Ti-6Al-7Nb (NS) surfaces, electropolished titanium (TE) and Ti-6Al-7Nb (NE) surfaces, and standard electropolished stainless steel (SS). Qualitative and quantitative results of S. aureus on the different surfaces correlated with each other, and showed significantly more live bacteria on NS than on the other surfaces, whilst there was no significant difference between the amount of bacteria on TS, TE, NE and SS surfaces. The results showed a significant decrease in the amount of bacteria adhering to the NE compared to standard NS surfaces. Such an observation suggests that the NS surface encouraged S. aureus adhesion, and could lead to higher infection rates in vivo. Hence electropolishing Ti-6Al-7Nb surfaces could be advantageous in osteosynthesis areas in minimising bacterial adhesion and lowering the rate of infection. PMID- 17268868 TI - Effect of gelatin on the drug release behaviors for the organic hybrid gels based on N-isopropylacrylamide and gelatin. AB - A series of organic hybrid gels were prepared based on poly(N isopropylacrylamide), poly(NIPAAm), and gelatin. The hybrid gels were crosslinked through a two-step process with genipin or glutaraldehyde. The swelling behavior and physical properties of the gels were investigated in the previous report. In this study, we loaded sulfanilamide, caffeine, vitamin B12, phenol red, and neutral red in the hybrid gels. The effects of gelatin on the drug release profile were demonstrated. The ionicity of hybrid gels strongly influenced the release of phenol red (anionic) and neutral red (cationic). However, the releases of sulfanilamide, caffeine and vitamin B12 were not influenced by the ionicity of hybrid gel. The drug released from the gels crosslinked with genipin was significantly smaller than that released from the gels crosslinked with glutaraldehyde. PMID- 17268869 TI - Impact of similarity in chemical composition of light-polymerized resin composites on post-gel strains and interface integrity. AB - The post-gel strains of two light-polymerized resin composites having similar chemical composition, Filtek P60 and Filtek Z250, was assessed by strain-gauge analysis at the ex vivo level. The restoratives were tested in cavity factor 5 during light-polymerization and water-soaking for 24 h. Strain-gauge signals were digitalized by a data acquisition system and were displayed in a computer by corresponding software at a sample rate of 20 Hz. The strain data were used to compare post-gel strains, polymerization velocity, and total volumetric change of both materials. Evaluation of microleakage and scanning electron microscopy was also undertaken to elucidate effects of post-gel strains at the tooth-restorative interface. Microstrains of Filtek Z250 were lower than those of Filtek P60 and the differences between post-gel strains at several different time intervals were significant (P < 0.009). There was a correlation between polymerization velocity and total volumetric change. Microleakage evaluation and scanning electron microscopy did not reveal any signs of debonding at the interface for both materials. We conclude that the similarity in chemical composition of light polymerized resin composites is not a determinant for post-gel strains. The tooth restorative interface can withstand high post-gel strains arising from polymerization of resin composites. PMID- 17268870 TI - Novel hydroxyapatite (HA) dual-scaffold with ultra-high porosity, high surface area, and compressive strength. AB - A novel scaffold designed for tissue engineering applications, which we refer to as a "dual-scaffold" because its structure consists of two interlaced three dimensional (3-D) hydroxyapatite (HA) networks, was fabricated using a combination of the rapid prototyping (RP) method and dip-coating process. To accomplish this, a graphite network acting as a template was prepared using the RP method and then uniformly dip-coated with HA slurry. The resultant sample was then heat-treated at 1250 degrees C for 3 h in air to remove the graphite network and consolidate the HA networks. An additional 3-D channel was formed by removing the graphite network, while preserving the pre-existing channel. The unique structure of the dual-scaffold endows it with unprecedented features, such as ultra-high porosity (>85%), a high surface area and high compressive strength, as well as a tightly controlled pore structure. In addition, an excellent cellular response was observed to the fabricated HA dual-scaffold. PMID- 17268871 TI - Preferential interactions of calcium ions in poly(2-hydroxyethyl methacrylate) hydrogels. AB - An investigation of the preferential interaction of calcium ions with oxygen atoms in poly(2-hydroxyethyl methacrylate) (PHEMA)-based hydrogels has been carried out. The formation of polymer-Ca complexes was achieved by exposing powdered or fully hydrated samples with 5 mM, 0.1-0.5 M, or saturated CaCl2 solutions for certain periods of time. The characteristics of the polymer-Ca complexes were deduced from the effect of the solute on the equilibrium water content, and from NMR, atomic absorption and infrared spectroscopies. The absence of significant changes in the NMR chemical shift and infrared vibrational wavenumbers for the various functional groups confirmed that polymer complexation with Ca2+ ions involves only weak interactions, possibly electrostatic or ion dipole interactions. Among the three types of oxygen atoms in PHEMA, hydroxyl oxygen atoms seem to be the most sensitive to the presence of Ca2+ ions. Complexation at the ester oxygen atoms was also evidenced by a new band in the infrared spectra at 1,550 cm(-1). On the other hand, there were no indications that the hydrophobic domains in the backbone and the methyl groups at the side chain of PHEMA interact significantly with Ca2+ ions. PMID- 17268873 TI - The influence of discharge power and heat treatment on calcium phosphate coatings prepared by RF magnetron sputtering deposition. AB - Ca-P coatings with different Ca/P ratio and composition were successfully prepared by RF magnetron sputtering deposition. The Ca/P ratio, phase composition, structure and morphological properties were characterized by XRD, FTIR, EDS and SEM analyses. All the as-sputtered coatings were amorphous and after IR-irradiation the coatings altered into a crystalline phase. The obtained coatings had a Ca/P ratio that varied from 0.55 to 2.10 and different phase compositions or mixtures of apatite, beta-pyrophosphate and beta tricalciumphosphate structures were formed. Evidently, the phase compositions of the sputtered coatings are determined not only by the discharge power ratio of the hydroxylapatite and calcium pyrophosphate targets but also by the annealing temperature. PMID- 17268872 TI - In vitro models of periodontal cells: a comparative study of long-term gingival, periodontal ligament and alveolar bone cell cultures in the presence of beta glycerophosphate and dexamethasone. AB - Human gingival (HG), periodontal ligament (HPL) and alveolar bone (HAB) cells (first subculture) were cultured (10(4) cells/cm2) for 35 days in alpha-Minimal Essential Medium supplemented with 10% fetal bovine serum in the presence of (i) ascorbic acid (AA, 50 microg/mL), (ii) AA + beta-glycerophosphate (betaGP, 10 mM) and (iii) AA + betaGP + dexamethasone (Dex, 10 nM). Cultures were assessed for cell attachment and spreading, cell proliferation, alkaline phosphatase (ALP) and acid phosphatase (ACP) activities and matrix mineralization. HG cell cultures presented a high proliferation rate, a low ability to synthesize ALP and ACP and the formation of a non-mineralized extracellular matrix, regardless the experimental situation. HPL cell cultures were very sensitive to the culture conditions and showed a high proliferation rate, synthesis of moderate levels of ALP and ACP and a modest matrix mineralization in the presence of AA + betaGP + Dex. HAB cell cultures presented a growth rate lower than that of HG and HPL cells, a high ALP activity and comparatively low levels of ACP, and the ready formation of a heavy mineralized matrix in the presence of betaGP. In the three periodontal cell cultures, Dex enhanced cell proliferation and expression of osteoblastic markers. Results showed that betaGP and Dex allowed the modulation of the cell proliferation/differentiation behavior within the proposed physiological and regenerative capabilities of these periodontal cells. PMID- 17268874 TI - Ectopic bone formation in cell-seeded poly(ethylene oxide)/poly(butylene terephthalate) copolymer scaffolds of varying porosity. AB - Scaffolds from poly(ethylene oxide) and poly(butylene terephthalate), PEOT/PBT, with a PEO molecular weight of 1,000 and a PEOT content of 70 weight% (1000PEOT70PBT30) were prepared by leaching salt particles (425-500 microm). Scaffolds of 73.5, 80.6 and 85.0% porosity were treated with a CO(2) gas plasma and seeded with rat bone marrow stromal cells (BMSCs). After in vitro culture for 7 days (d) in an osteogenic medium the scaffolds were subcutaneously implanted for 4 weeks in nude mice. Poly(D, L-lactide) (PDLLA) and biphasic calcium phosphate (BCP) scaffolds were included as references. After 4 weeks (wks) all scaffolds showed ectopic formation of bone and bone marrow. For the scaffolds of different porosities, no significant differences were observed in the relative amounts of bone (7-9%) and bone marrow (6-11%) formed, even though micro computed tomography (mu-CT) data showed considerable differences in accessible pore volume and surface area. 1000PEOT70PBT30 scaffolds with a porosity of 85% could not maintain their original shape in vivo. Surprisingly, 1000PEOT70PBT30 scaffolds with a porosity of 73.5% showed cartilage formation. This cartilage formation is most likely due to poorly accessible pores in the scaffolds, as was observed in histological sections. mu-CT data showed a considerably smaller accessible pore volume (as a fraction of the total volume) than in 1000PEOT70PBT30 scaffolds of 80.6 and 85.0% porosity. BMSC seeded PDLLA (83.5% porosity) and BCP scaffolds (29% porosity) always showed considerably more bone and bone marrow formation (bone marrow formation is approximately 40%) and less fibrous tissue ingrowth than the 1000PEOT70PBT30 scaffolds. The scaffold material itself can be of great influence. In more hydrophobic and rigid scaffolds like the PDLLA or BCP scaffolds, the accessibility of the pore structure is more likely to be preserved under the prevailing physiological conditions than in the case of hydrophilic 1000PEOT70PBT30 scaffolds. Scaffolds prepared from other PEOT/PBT polymer compositions, might prove to be more suited. PMID- 17268875 TI - PDMS content affects in vitro hemocompatibility of synthetic vascular grafts. AB - An unsolved problem when employing small-diameter vascular grafts for aorto coronary by-pass and peripheral reconstruction is the early thrombotic occlusion. The PEtU-PDMS is a new elastomeric material, composed of poly(ether)urethane and polydimethylsiloxane, synthesized to realize grafts with improved hemocompatibility characteristics. In order to investigate the effect of PDMS content on hemocompatibility, three different percentages of PDMS containing grafts (10, 25 and 40) were evaluated. Grafts realized with Estane 5714-F1 and silicone medical grade tubes were used as references. The hemocompatibility was investigated by an in vitro circuit in which human anticoagulated blood was circulated into grafts by a peristaltic pump modified to obtain a passive flow. For each experiment, 40 cm length graft was closed into a circular loop and put in rotation for 2 h at 37 degrees C. At the end of the experiments different parameters regarding platelet adhesion and activation were evaluated: circulating platelets count, beta-thromboglobulin release, platelet CD62P expression and amount of monocyte-platelet conjugates. PEtU-PDMS grafts with 25 and 40% of PDMS induced the lowest platelet adhesion, plasma level of beta-TG and amount of monocyte-platelet conjugates. No significative variations were observed in CD62P expression. In conclusion, PDMS content significatively affects blood-graft surface interaction, in fact higher PDMS percentage containing grafts showed the best in vitro hemocompatibility. PMID- 17268876 TI - Mechanical failure of a Thompson's hemiarthoplasty stem 28 years post implantation: an investigation with electron microscopy. AB - Tauhe authors would like to report a mechanical failure of a Thompson's prosthesis, 28 years post-implantation. A detailed examination of the specimen revealed no defects in the prosthesis and a dominating 'brittle component' fracture of the stem. In this context the detailed fractographic study by scanning electron microscopy (SEM) revealed no detrimental manufactural defects that may have produced microcracks and consequently risked initiating the fracture propagation. In contrast, the fracture was mainly a fatigue one with a mixed mode of microscopic trans- and intergranular crack propagation. To the best of our knowledge, such a mechanism of implant failure in a cementless stem has never before reached 28 years neither in a Thompson's nor any other type of prosthesis, and in the already reported case, it exceeded 30 years [N. Wolson and J. P. Waadell, Can. J. Surg. 38(6) (1995) 542], however the stem's ultrastructure has never been investigated under electron microscopy, which arguably can provide a useful assessment of a fatigue fracture. Tauhe authors introduce the question of revising our standards when evaluating the newly designed and expensive implants and propose re-focusing on surgical technique, rather than purely on implant properties. PMID- 17268877 TI - The relationship between vigorous physical activity and juvenile delinquency: a mediating role for self-esteem? AB - Many policy-related reviews of the potential social value of sport and physical activity list the prevention of juvenile delinquency. We examined the relationships among vigorous physical activity, self-esteem, and delinquent behavior among adolescents in a large cross-sectional survey of Ontario adolescents. Data are based on questionnaires from 3,796 students (range 11-20 years) derived from the 2005 Ontario Student Drug Use Survey. Negative binominal regression methods were used to estimate both additive and interactive models predicting delinquent behavior. Vigorous physical activity was positively associated with delinquent behavior; however, this pattern of association was observed only among male adolescents. There was no evidence of a mediating role for self-esteem. Our findings suggest that physical activity is not the solution for reducing juvenile delinquency. PMID- 17268878 TI - Pessimism and physical functioning in older women: influence of self-efficacy. AB - The purpose of the present study was to examine the nature of the relationships among dispositional optimism/pessimism, self-efficacy, and physical function in a cross-sectional sample of older women (N = 249, M age = 69 years). Initial bivariate analyses indicated that both pessimism and self-efficacy, but not optimism, were significantly correlated with objectively measured physical function. Subsequent analyses using covariance modeling with the full-information maximum likelihood estimator indicated that pessimism was no longer correlated with function when controlling for self-efficacy. That is, consistent with a social cognitive perspective, controlling for self-efficacy attenuated the relationship between pessimism and function. Our findings provide support for using a social cognitive perspective to understanding dispositional and modifiable influences on declines in function associated with aging. PMID- 17268879 TI - Urea transformation of wetland microbial communities. AB - Transformation of urea to ammonium is an important link in the nitrogen cycle in soil and water. Although microbial nitrogen transformations, such as nitrification and denitrification, are well studied in freshwater sediment and epiphytic biofilm in shallow waters, information about urea transformation in these environments is scarce. In this study, urea transformation of sedimentary, planktonic, and epiphytic microbial communities was quantified and urea transformation of epiphytic biofilms associated with three different common wetland macrophyte species is compared. The microbial communities were collected from a constructed wetland in October 2002 and urea transformation was quantified in the laboratory at in situ temperature (12 degrees C) with the use of the 14C urea tracer method, which measures the release of 14CO2 as a direct result of urease activity. It was found that the urea transformation was 100 times higher in sediment (12-22 mmol urea-N m(-2) day(-1)) compared with the epiphytic activity on the surfaces of the submerged plant Elodea canadensis (0.1-0.2 mmol urea-N m(-2) day(-1)). The epiphytic activity of leaves of Typha latifolia was lower (0.001-0.03 mmol urea-N m(-2) day(-1)), while urea transformation was negligible in the water column and on the submerged leaves of the emergent plant Phragmites australis. However, because this wetland was dominated by dense beds of the submerged macrophyte E. canadensis, this plant provided a large surface area for epiphytic microbial activity-in the range of 23-33 m2 of plant surfaces per square meter of wetland. Thus, in the wetland system scale at the existing plant distribution and density, the submerged plant community had the potential to transform 2-7 mmol urea-N m(-2) day(-1) and was in the same magnitude as the urea transformation in the sediment. PMID- 17268880 TI - Development and structure of eukaryotic biofilms in an extreme acidic environment, rio tinto (SW, Spain). AB - An in situ colonization assay was performed to study the early stages of biofilm formation in Rio Tinto (SW, Spain), an extremely acidic environment (pH ca. 2). Eukaryotic assemblages were monitored at monthly intervals for 1 year. Diversity, colonization rates, and seasonal variations were analyzed. Structural features of naturally grown biofilms were explored by light and scanning electron microscopy in backscattered electron mode. A total of 14 taxa were recognized as constituents of the eukaryotic assemblages. The eukaryotic communities were dissimilar at the different sampling sites. The lowest diversity was found at the most extreme locations, in terms of pH and heavy metal concentrations. The biofilms were mainly formed by species from the genera Dunaliella and Cyanidium. Two genera of filamentous algae, Zygnemopsis and Klebsormidium, were principally responsible for the variability in the cell number throughout the year. These species appear in June to decrease almost completely between October and November. In contrast, the number of heterotrophic flagellates and ciliates remained constant throughout the year. The microcolonization sequence showed an initial accumulation of amorphous particles composed of bacteria and inorganic grains of minerals. By the end of the second month, the organic matrix was also populated by fungi, bacteria, and a few eukaryotic heterotrophs such as amoebae and small flagellates. Diatoms only showed significant colonization in regions where mycelial matrices were first established. Flagellated green algae such as Dunaliella or Chlamydomonas as well as Euglena were also present at the very beginning of the biofilm development, although in low numbers (<100 cells cm( 2)). After the flagellated cells, sessile species of algae such Chlorella or Cyanidium appeared. Filamentous algae were the last species to colonize the biofilms. Most of the naturally grown biofilms were found to be structures composed of different species organized in different layers separated, probably by extracellular polymeric substances, although more analysis should be done in this regard. The possible implications of the biofilm structure in the adaptation to this extreme habitat are discussed. PMID- 17268882 TI - Reoperative sentinel lymph node biopsy: a new frontier in the management of ipsilateral breast tumor recurrence. AB - BACKGROUND: Breast conservation therapy (BCT) with sentinel lymph node (SLN) biopsy is a well-established standard of care for primary operable breast cancer; 5-10% of BCT patients will develop local recurrence (LR). The question then arises: How best to manage the axilla in the setting of LR after previous BCT and SLN biopsy or axillary dissection (ALND)? METHODS: Between 9/96 and 12/04, 117 reoperative SLN were performed for LR after BCT and either SLN biopsy or ALND more than 6 months previously. Because of wide variation in the number of nodes removed at the initial procedure, validation by backup ALND was not feasible in all cases. RESULTS: Reoperative SLN was successful in 64/117 (55%) patients. SLNs were identified by isotope and dye in 28/64 (44%); isotope only in 29/64 (45%); dye only in 4/64 (6%); 3/64 (5%) unknown. Positive reoperative SLN were found in 10/64 (16%) successful cases. Among 54/64 (84%) patients with negative reoperative SLNs, 23 (43%) had additional non-SLN removed concurrently: these were negative in 21/23 cases (91%). In 2/23 (9%), reoperative SLN were falsely negative: one with a positive intramammary node, and the other with a positive non-SLN palpated at surgery. Success of reoperative SLN was inversely related to number of nodes removed previously, and was more likely to be successful after a previous SLN biopsy than a previous ALND (74% vs. 38%, P = 0.0002). Non-axillary drainage was identified by lymphoscintigraphy significantly more often in reoperative SLN than in primary SLN biopsy (30% vs. 6%, P < 0.0001). There were no local or axillary recurrences at a mean follow up of 2.2 years; 6 patients developed systemic recurrence. CONCLUSIONS: Reoperative SLN biopsy is feasible in the setting of LR after previous BCT/axillary surgery and deserves further study in this increasingly common clinical scenario. The added benefit of lymphoscintigraphy in identifying sites of non-axillary drainage may be greater in the setting of reoperative SLN than for the initial SLN procedure. PMID- 17268883 TI - The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC): a postal survey of UK families. AB - Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder associated with a wide range of physical features and very high rates of numerous neurocognitive manifestations. However, there is great variability of expression of these features and understanding of the mechanisms underlying this variability is still limited. Mental retardation (MR) and male gender are known to be associated with increased risks of psychopathologies in the general population, but no study has examined these subgroups in TSC as possible contributors to the variable expression observed. It has also remained unclear whether familial sporadic differences may contribute to variable expression. In this postal survey, UK families reported the frequency and range of physical and behavioural abnormalities in 265 children and adolescents with TSC. Analysis revealed no gender or familial-sporadic differences. Children with MR were significantly more likely to have an autism spectrum disorder, attention deficit-related symptoms and speech and language difficulties. They were more likely to have a history of epilepsy, facial angiofibromata and shagreen patches and tended to have a greater number of physical features of the disorder. However, about one third of the children without MR had features suggestive of a developmental disorder. Anxiety symptoms, depressed mood and aggressive outbursts occurred at equally high rates in those with and without MR. These findings show that TSC can place any child or adolescent at significantly increased risk of a range of neurodevelopmental disabilities. These difficulties, often not recognised, require significant clinical and research attention. PMID- 17268884 TI - Hemihypomimia, a rare persistent sign in Parkinson's disease: follow up of 11 patients. AB - BACKGROUND: Typical hypomimia develops in almost all Parkinson's disease (PD) patients. We observed the presence of hemihypomimia (HH) in some of our PD patients. OBJECTIVE: To discern the presence of hemihypomimia, to compare clinical features of these patients with the patients without HH and then to evaluate HH prospectively. METHODS: Among 353 patients with PD followed-up between September 2003 and December 2004, 204 patients in stage 2 of Hoehn-Yahr were evaluated and hemihypomimia was observed in 13 PD patients (6.4%). Two groups were compared with respect to the age of onset of the first PD symptom, duration of PD and the body side affected predominantly. In addition, persistence of HH was prospectively evaluated in 11 of 13 patients with HH up to two-year follow up period. RESULTS: Hemihypomimia was interestingly on the right side of the face in all patients. Of these 13 HH patients, all but one had predominantly right-sided PD symptomatology. In the comparison of HH patients with the remaining group (n=191), patients with HH had significantly earlier onset of PD symptoms (mean: 53.9 vs 58.5 years), and shorter PD duration (mean: 4.0 vs 6.2 years) (p<0.01). Up to two-year-follow up, hemihypomimia, which was not changed by several triggered emotional facial expressions, clinically persisted. CONCLUSION: Our observations suggest that hemihypomimia is a rare phenomenon in PD, especially in PD patients having early-onset and shorter PD duration which may persist for several years in concordance with typical asymmetrical involvement of the limbs. HH developed in the right side, prominently on the lower part of the face. Understanding the underlying mechanism(s) about how hemihypomimia appears, and why it dominantly affects the right side of the face deserves further assessment. PMID- 17268885 TI - Myocardial protection evoked by hyperoxic exposure involves signaling through nitric oxide and mitogen activated protein kinases. AB - BACKGROUND: Hyperoxic exposure in vivo (> 95% oxygen) attenuates ischemia reperfusion injury, but the signaling mechanisms of this cardioprotection are not fully determined. We studied a possible role of nitric oxide (NO) and mitogen activated protein kinases (MAPK) in hyperoxic protection. METHODS: Mice (n = 7-9 in each group) were kept in normoxic or hyperoxic environments for 15 min prior to harvesting the heart and Langendorff perfusion with global ischemia (45 min) and reperfusion (60 min). Endpoints were cardiac function and infarct size. Additional hearts were collected to evaluate MAPK phosphorylation (immunoblot). The nitric oxide synthase inhibitor L-NAME, the ERK1/2 inhibitor PD98059 and the p38 MAPK inhibitor FR167653 were injected intraperitoneally before hyperoxia or normoxia. RESULTS: Hyperoxia improved postischemic functional recovery and reduced infarct size (p < 0.05). Hyperoxic exposure caused cardiac phosphorylation of the MAPK family members p38 and ERK1/2, but not JNK. L-NAME, PD98059 and FR167653 all reduced the protection afforded by hyperoxic exposure, but did not influence performance or infarction in hearts of normoxic mice. The hyperoxia-induced phosphorylation of ERK1/2 and p38 was reduced by L-NAME and both MAPK inhibitors. CONCLUSION: Nitric oxide triggers hyperoxic protection, and ERK1/2 and p38 MAPK are involved in signaling of protection against ischemia reperfusion injury. PMID- 17268886 TI - Preoperative unstable angina causes venous adaptation to surgical graft injury. AB - Ischemic preconditioning may provide a systemic organ protection, evident as the phenomenon known as remote preconditioning. Unstable angina may be a clinical analogue to ischemic preconditioning. Vein graft harvesting induces inflammation of the graft wall. We hypothesized that preoperative unstable angina preconditions vein grafts and reduces the inflammatory response to graft harvesting. Consecutive patients with stable or unstable angina undergoing open heart surgery (n = 12 in each group) were studied. Saphenous vein biopsies were collected at the start of graft harvesting, and when the last proximal anastomosis to the aorta was finished (average 112 minutes later). Gene expression of inflammatory mediators (tumor necrosis factor alpha, interleukin 1beta (IL-1beta), E-selectin (CD62E), intercellular leukocyte adhesion molecule 1, inducible nitric oxide synthase, endothelin-1) increased after surgical handling (semiquantitative RT-PCR). In vein grafts from unstable patients the increase was attenuated for Il-1beta (p < 0.004) and CD62E (p < 0.001). In stable patients the protein expression of IkappaBalpha and heat shock protein72 was reduced by surgical handling (p < 0.04), but was not influenced in unstable patients (immunoblotting). In vitro relaxation to acetylcholine was enhanced, and contractions to phenylephrine and endothelin-1 were attenuated in veins rings from unstable patients (p < 0.003). In conclusion, surgical handling of vein grafts induces inflammation of the vessel wall. This response was reduced in grafts from patients with unstable angina, indicating a possible systemic preconditioning-like effect of acute coronary syndromes. PMID- 17268887 TI - The effects of cilazapril and valsartan on the mRNA and protein expressions of atrial calpains and atrial structural remodeling in atrial fibrillation dogs. AB - Owing to relative inefficacy and side effects of currently available antiarrhythmic drugs, current interest has shifted to treatments that target atrial fibrillation (AF) substrate. It has been suggested that calpain-induced atrial structural remodelling is under the control of renin-angiotensin system during AF. The purpose of this study is to investigate the effects of cilazapril and valsartan on the mRNA and protein expression of atrial calpains and atrial structural remodelling in AF dogs induced by chronic rapid atrial pacing. Twenty seven dogs were randomly divided into sham-operated group (n = 6), control group (n = 7), cilazapril group (n = 7) and valsartan group (n = 7). One thin silicon plaque containing 4 pairs of electrodes was sutured to each atrium. A pacemaker was implanted in a subcutaneous pocket and attached to a screw-in epicardial lead in the right atrial appendage. The dogs in control group, cilazapril group and valsartan group were paced at 400 beats per minutes for 6 weeks. The dogs in cilazapril and valsartan groups received cilazapril (1mg x kg(-1)x d(-1)) or valsartan (30mg x kg(-1) x d(-1)) 1 week before rapid atrial pacing until pacing stop respectively. Transthoracic and transoesophageal echocardiographic examinations were performed in order to detect the changes of left atrium volume and contractile function. The inducibility and duration of AF were measured in all the groups. The expressions of atrial calpain I and calpain II mRNA were semi quantified by reverse transcription-polymerase chain reaction. The protein levels of calpain I and calpain II in atrial myocardium were measured by Western-blot method. Pathohistological and ultrastructural changes in atrial tissue were tested by light and electron microscopy. Compared with the sham-operated control group, dramatic smaller left atrium and left atrial appendage volumes and significant higher atrial contractile function were observed in the cilazapril and valsartan groups. After 6-week atrial tachy-pacing, the mRNA and protein expressions of calpain I increased dramatically in the control group than that in the sham group, tissue calpain protein expression in all groups significantly correlated with the myolysis (r = 0.89, P < 0.01). Cilazapril and valsartan could significantly inhibit the gene and protein expressions of calpain I. No differences were found in the expression of calpain II mRNA and protein between the groups. Compared with atrial myocytes obtained from sham dogs, atrial myocytes from the control group dogs showed a reduced number of sarcomeres, a significant higher myolytic area of atria (24.3% vs. 3.1%, P < 0.01), increased vacuolization and dissolution. Cilazapril and valsartan could effectively prevent the pathohistological and ultrastructural changes induced by chronic rapid atrial pacing, dramatically decrease the area of myolysis (P < 0.05) and significantly reduce the inducibility and duration of AF. The expression of calpain I mRNA and protein increased remarkably in AF dogs. Cilazapril and valsartan can inhibit calpain I up-regulation, suppress atrial structural remodeling, and prevent the induction and promotion of AF in chronic rapid atrial pacing dogs. PMID- 17268888 TI - The hypoxia-inducible factor HIF-1 promotes intramyocardial expression of VEGF in infants with congenital cardiac defects. AB - OBJECTIVES: The response to hypoxia is primarily mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1) which leads to the induction of a variety of adaptive gene products including vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). This study was designed to test the hypothesis that HIF-1 and its target genes would be upregulated in the ventricular myocardium of infants with cyanotic congenital cardiac defects. METHODS: 14 infants with cyanotic (n = 7) or acyanotic cardiac defects (n = 7) were investigated. Samples from the right ventricular myocardium taken immediately after aortic clamping were studied for protein expression and DNA binding activity. RESULTS: Protein levels of HIF-1alpha were significantly elevated in patients with cyanotic compared to acyanotic congenital heart disease and inversely correlated with the degree of hypoxemia. This response was accompanied by significantly enhanced HIF-1 DNA binding activity. Furthermore, protein levels of VEGF and eNOS were significantly higher in the myocardium of cyanotic than of acyanotic infants. To test the potential involvement of upstream regulatory pathways, activation of MAP kinases was determined. Intramyocardial levels of phosphorylated p38 MAP kinase, but not of ERK1/2 were significantly higher in infants with cyanotic compared to those with acyanotic congenital heart disease and inversely correlated to hypoxemia. CONCLUSIONS: These findings show that chronic hypoxemia is associated with the induction and stabilization of the transcription factor HIF-1 as well as its target genes VEGF and eNOS in the myocardium of infants with cyanotic cardiac defects. Thus, stabilization of HIF-1 and induction of the adaptive hypoxia response could particularly participate in myocardial remodeling in children with congenital cardiac defects and chronic hypoxemia. PMID- 17268889 TI - Identification of genes associated with flesh morphogenesis during grapevine fruit development. AB - Fruit morphogenesis is a process unique to the angiosperms, and yet little is known about its developmental control. Following fertilization, fruits typically undergo a dramatic enlargement that is accompanied by differentiation of numerous distinct cell types. To identify genes putatively involved in the early development of grapevine fruit, we used the fleshless berry mutant (Vitis vinifera L. cv Ugni Blanc) that has dramatically reduced fruit size due to a lack of pericarp development. Using oligo-specific arrays, 53 and 50 genes were identified as being down- and up-regulated, respectively, in the mutant. In parallel, Suppression Subtractive Hybridization performed between the mutant and the wild type (WT) allowed the identification of new transcripts differentially expressed during the first stages of mutant and WT pericarp development. From this data, the picture emerged that the mutation promotes the expression of several genes related to ripening and/or to stress and impairs the expression of several regulatory genes. Among those, five genes encoding proteins previously reported to be associated with, or involved in, developmental processes in other species (a specific tissue protein 2, ATHB13, a BURP domain protein, PISTILLATA, and YABBY2), were identified and investigated further using real-time PCR and in situ hybridization. Expression in the pericarp was confirmed, specific spatial and/or temporal patterns were detected and differences were observed between the WT and the mutant during fruit development. Expression of these genes appeared to be affected during young fruit development in the mutant, suggesting that they may play a role in grape berry morphogenesis. PMID- 17268890 TI - Growth characteristics of Saccharomyces cerevisiae S288C in changing environmental conditions: auxo-accelerostat study. AB - The effect of individual environmental conditions (pH, pO(2), temperature, salinity, concentration of ethanol, propanol, tryptone and yeast extract) on the specific growth rate as well as ethanol and glycerol production rate of Saccharomyces cerevisiae S288C was mapped during the fermentative growth in aerobic auxo-accelerostat cultures. The obtained steady-state values of the glycerol to ethanol formation ratio (0.1 mol mol(-1)) corresponding to those predicted from the stoichiometric model of fermentative yeast growth showed that the complete repression of respiration was obtained in auxostat culture and that the model is suitable for calculation of Y(ATP) and Q(ATP) values for the aerobic fermentative growth. Smooth decrease in the culture pH and dissolved oxygen concentration (pO2) down to the critical values of 2.3 and 0.8%, respectively, resulted in decrease in growth yield (Y(ATP)) and specific growth rate, however the specific ATP production rate (Q(ATP)) stayed almost constant. Increase in the concentration of biomass (>0.8 g dwt l(-1)), propanol (>2 g l(-1)) or NaCl (>15 g l(-1)) lead at first to the decrease in the specific growth rate and Q(ATP), while Y(ATP) was affected only at higher concentrations. The observed decrease in Q(ATP) was caused by indirect rather than direct inhibition of glycolysis. The increase in tryptone concentration resulted in an increase in the specific growth rate from 0.44 to 0.62 h(-1) and Y(ATP) from 12.5 to 18.5 mol ATP g dwt(-1). This study demonstrates that the auxo-accelerostat method, besides being an efficient tool for obtaining the culture characteristics, provides also decent conditions for the experiments elucidating the control mechanisms of cell growth. PMID- 17268891 TI - RAPD typing of Aspergillus chevalieri, Aspergillus nidulans, Aspergillus tetrazonus (quadrilineatus) and their teleomorphs using 5'-d[AACGCGCAAC]-3' and 5'-d[CCCGTCAGCA]-3' primers. AB - Sexuality in fungi has long been a matter of concerns and debates that always necessitated extensive analysis of the relationship between organisms assumed to represent different developmental forms of the same organism. Moreover, mating virulence correlation and the growing worry of opportunistic fungal infections in immunocompromised states associated with AIDS, cancer chemotherapy and organ transplantation protocols have been critically addressed nowadays. In view of that, we genetically characterized Aspergillus chevalieri, Aspergillus nidulans, Aspergillus tetrazonus (quadrilineatus) and their teleomorphs with RAPD analysis using 5'-d[AACGCGCAAC]-3' and 5'-d[CCCGTCAGCA]-3' primers. The reported similarities between the sexual and the asexual forms of the tested species, using Dice coefficient, ranged between 40% and 70% which holds pretty much with the current systematics of the genus. The study presents a rapid consistent method for identification of A. chevalieri, A. nidulans, A. tetrazonus (quadrilineatus) and their teleomorphs based on the banding pattern of RAPD generated fragments that can be reliably used ahead of further applications on these species. PMID- 17268892 TI - Purple urine bag syndrome: a rare clinical entity in patients with long term indwelling catheters. AB - An elderly gentleman, on urinary drainage catheter for 3 months developed a purple discoloration of the urinary bag with the urine inside remaining clear. He was found to have a urinary tract infection with a strain of E. coli manifesting as a rare clinical entity reported in literature as the "Purple urine bag syndrome". PMID- 17268893 TI - Nephrobronchial fistula - a case report. AB - We report the case of a 58-year-old woman with a hydronephrotic left kidney who presented with a 4-month history of anorexia, weight loss and intermittent left loin pain associated with cloudy urine. Her urine grew lactose fermenting coliforms, and was treated with antibiotics. A computerized axial tomography scan (CT scan) was equivocal and she underwent retrograde ureteric stenting, which drained a pyonephrosis. She went on to develop a chest infection due to a lung abscess. A CT scan revealed a left perinephric collection extending across the diaphragm into the lower lobe of the left lung. She responded to antibiotics and awaits a nephrectomy. PMID- 17268894 TI - The efficacy of duloxetine in the treatment of premature ejaculation. AB - AIM: Though premature ejaculation (PE) has been overshadowed by current attention given to erectile dysfunction, it is the most widespread form of male sexual dysfunction. Delayed or inhibited ejaculation, a known side effect of selective serotonin reuptake inhibitors (SSRIs), has made SSRIs potentially useful in the treatment of this disorder. In the present study, we examined the efficacy of duloxetine, an SSRI, in the treatment of PE. METHOD: The study included 20 married patients diagnosed with PE. The patients were randomly assigned to two groups, duloxetine (group I) and placebo (group II), each consisting of 10 patients. The effects on the ejaculatory function were estimated by the intravaginal ejaculation latency time. All patients were evaluated by using clinical global impression-improvement Scale (CGI-I). RESULTS: The increase in the intravaginal ejaculation latency time in the duloxetine group was statistically significant than that of placebo group. Of group I patients, four (40%) were considered as "very much improved" and four (40%) "much improved" by CGI-I and only one of group II patients (10%) showed "much improved". CONCLUSION: Duloxetine appears to be superior to placebo in the pharmacological treatment of PE when administered on a chronic basis. PMID- 17268895 TI - An unusual case of Von Hipple Lindau (VHL) syndrome with bilateral multicentric renal cell carcinoma with synchronous solitary urinary bladder metastasis. AB - In VHL syndrome, renal cell carcinoma is distinctive for its early age of onset, for its bilateral and multifocal involvement. Synchronous solitary urinary bladder metastasis from renal cell carcinoma is extremely rare. We report an unusual case of VHL with bilateral multicentric renal cell carcinoma and synchronous solitary urinary bladder metastasis. To the best of our knowledge this is the first case reported in literature with this combination. PMID- 17268896 TI - Trans-rectal ultrasound guided biopsy of the prostate: nationwide diversity in practice and training in the United Kingdom. AB - INTRODUCTION: TRUS-guided needle biopsy of the prostate is the standard technique in the diagnosis of prostate cancer. However the practice is highly variable across the United Kingdom. We survey the standard approaches to TRUS biopsy of prostate, highlighting the nationwide diversity of practice and training. METHODS: One hundred and eighty questionnaires were sent out to specialist registrars, investigating the number of prostate biopsy cores taken, the use of prophylactic antibiotics, rectal preparation and local analgesia in TRUS biopsy of the prostate. One hundred and fourteen trainees (63%) returned the questionnaires. Twenty-three percent reported sextant biopsy as standard, 36% taking eight-core and 26% taking 10 or more cores. There is no standard regime for antibiotic prophylaxis. Eighteen percent also reported rectal preparation as routine. Thirty-eight percent of the patients receive local anaesthesia prior to the biopsy. Overall, 42% of the TRUS biopsies are carried out by urologists, 29% by radiologists and 21% by both. Six percents have nurse practitioners' involvement. Fifty-six percent of trainees are involve in the TRUS biopsy, 68% do not think they received enough training to carry out the procedure. CONCLUSIONS: TRUS-guided needle biopsy of the prostate is the standard technique in the diagnosis of prostate cancer. Our survey highlights nationwide diversity in practice in the UK with respect of the number of cores taken, antibiotic prophylaxis and local anaesthesia utilisation. This raised the issue of standardising the practice. More urologists are also actively taking part in this procedure, making the structured training increasingly important. PMID- 17268897 TI - Prediction of success of extracorporeal shock wave lithotripsy in the treatment of ureteric stones. AB - OBJECTIVES: To define the factors that affect the success rate of extracorporeal shock wave lithotripsy (ESWL) for the treatment of ureteric stones. PATIENTS AND METHODS: Between January 2000 and December 2003, 468 patients with ureteric stones underwent in situ ESWL using Storz SL 20 lithotriptor. The results of treatment were evaluated after 3 months of follow-up. Treatment success was defined as complete clearance of the stones. Characteristics of the patients, condition of the urinary tract and stone features were correlated to the success rate to define the significant predictors of success. RESULTS: At 3-month follow up, the overall success rate was 394/468 (84.2%). Repeat treatment was required in 239 patients (51.1%). Post-ESWL auxiliary procedures were necessary in 58 patients (12.4%). Post-ESWL complications were observed in 11 patients (2.4%). Only three factors had a significant impact on the stone-free rate, namely stone site, stone width and the presence of a ureteral stent. The stone-free rate was highest for stones located in the lumbar ureter (159/183; 86.9%) and lowest for those in iliac ureter (28/40; 70%) (P < 0.05). Stones with a transverse diameter <8 mm were associated with a stone-free rate of 89.9% (248/276), compared to 66.7% (128/192) for those with a transverse diameter of >8 mm (P < 0.01). Non stented patients had a stone-free rate of 89.2% (313/348), compared to 75.2% (85/113) for stented patients (P < 0.01). CONCLUSIONS: The site and transverse diameter of the stone and the presence of a ureteral stent are the only significant predictors of success of ESWL therapy for ureteric stones. PMID- 17268898 TI - Traumatic renal hydatid cyst rupture: report of a case. AB - In this case report we present a 30-year-old male patient, who had renal hydatid cyst rupture due to blunt abdominal trauma. The case is presented and the relevant literature is reviewed and discussed. Despite its rarity, traumatic renal hydatid cyst rupture should be kept in mind in the differential diagnosis of a blunt abdominal trauma in the endemic area. PMID- 17268899 TI - Isolated renal hydatic cyst; from an unusual course to diagnosis. AB - An isolated renal cyst hydatic in a 65 year old man with unusual symptomatology, course and complications were presented. PMID- 17268900 TI - Adult bilateral non-obstructing orthotopic ureteroceles with multiple calculi: endoscopic management with review of literature. AB - We describe and report two cases of bilateral symptomatic ureterocele with calculi in two young adult women. They were successfully managed endoscopically by a transverse meatotomy and stone extraction done bilaterally in a single operative session. The 6th month postoperative voiding cystourethrogram showed no reflux. The literature regarding the incidence, occurrence, diagnosis and management of this uncommon condition in adults has been reviewed and discussed. PMID- 17268901 TI - The effect of ABO-Rh blood group determinants on urinary tract infections. AB - BACKGROUND: Blood group antigens are a group of carbohydrate determinants found on erythrocytes, phagocytes, lymphocytes and certain epithelial tissues including urothelium. There are several publications that defines enhanced bacterial adhesions due to genetic markers such as blood group types. METHODS: The ABO-Rh blood group distribution of patients with UTI and Escherichia coli(+) urine culture were compared with ABO-Rh blood group distribution of our country. RESULTS: The distribution of blood groups was as follows; 36.6% A Rh+, 4.9% A Rh , 12.2% B Rh+, 2.4% B Rh-, 31.7% O Rh+, 2.4% O Rh-, 4.9% AB Rh+, respectively; and none with AB Rh- blood group. There was a significant correlation between our study group and ABO-Rh phenotypes distribution of Turkish population. CONCLUSIONS: The concordance of UTI with blood group ARh+ may be due to the most seen of ARh+ phenotype in the investigated population. We suggest that before defining the relationships on genetical markers, it would be more reliable to correlate them with their local distributions in the population. PMID- 17268902 TI - Effects of specific inhibition of cyclooxygenease-2 on kidney in bilateral adrenalectomized rats. AB - In the kidney, prostaglandins represent important physiological modulators of renal hemodynamics and salt and water homeostasis. In this experimental study of bilaterally adrenalectomized (ADX) rats, we aimed to investigate whether the administration of selective (celecoxib) inhibitor of COX-2 would alter the morphological and functional changes in rat kidney tissue. Twenty-one male Sprague-Dawley rats weighing 225-250 g were used. The animals were divided into three groups. Group 1 rats (Sham-control, n = 7) did not receive any treatment. In group 2 rats (ADX/Untreated, n = 7), bilateral ADX was performed via a single dorsal incision. In group 3 (ADX/COX-2) rats, the same operation was performed as described for group 2 and then the COX-2 inhibitor celecoxib was administered by gavage for a period of 7 days. On the 7th day of the study, renal function was assessed by measurements of blood urea nitrogen (BUN) and serum creatinine levels. Biopsies were obtained from the remaining left kidneys before killing the rats. There was no significant difference in the BUN and creatinine values between the groups. In ADX/Untreated group, capillary congestion in glomerule, inflammation, hemorrhage and congestion in intertubular area, and cytoplasmic vacuolation in renal tubules was observed. Mild damage was observed in the ADX/COX-2 group. The number of macrophages was significantly decreased in ADX/COX 2 group when compared to ADX/Untreated group (P < 0.0001). Our study indicates that celecoxib may be an important factor affecting renal morphological changes after the bilaterally ADX. PMID- 17268903 TI - Modification of retropubic adenomectomy: improved hemostasis and outcome. AB - INTRODUCTION: Our modification is based on the employment of the ligation of both the deep dorsal penile vein (DDPV) and the lateral vesicoprostatic pedicles before enucleation of adenoma in retropubic adenomectomy, for treatment of bladder outflow obstruction due to large benign prostate hyperplasia (BPH). PATIENTS AND METHODS: From January 2004 till May 2005, 18 patients suffering from large BPH obstruction (mean value of adenoma 145.4 cm(3)) were operated with this modification. RESULTS: The mean hematocrit values preoperatively and 12 h postoperatively were 40 and 36.6%, respectively. Accordingly no patient required transfusion. Postoperative bladder complaints (pain, discomfort) were not mentioned. In 3/18 (16.7%) of the patients transient stress incontinence was observed after catheter removal and totally subsided in all of them at the 1 month follow up. DISCUSSION: This modification eliminates any possible source of bleeding and therefore converts an operation which is traditionally associated with blood loss to a totally bloodless procedure. Furthermore, the ligation of DDPV in association to retropubic adenomectomy may be proved helpful in a proportion of patients with impotence. CONCLUSION: In experienced hands, the employment of both DDPV ligation and transfixion of lateral vesicoprostatic pedicles may significantly optimise the postoperative results of retropubic adenomectomy. PMID- 17268904 TI - Unexpected, severe central nerve system toxicity of ofloxacine: report of two cases. AB - Central nerve system toxicity of fluoroquinolones is well known but nearly always benign. Old age, concomittant central nerve system disease, drug interactions and/ or partial or total loss of renal function are the major risk factors. Although, in literature there is very limited number of severe central nerve system toxicity cases related to fluoroqinolones, prompt realization is vital as the only therapy is discontinuation of the drug. In this article, two cases of acute central nerve system toxicity of ofloxacin with an unexpected severity are described. PMID- 17268905 TI - Multicystic dysplastic kidney and caliceal diverticulum in a child a coincidence or an association? PMID- 17268906 TI - Adult Wilms' tumor: a case report and review of literature. AB - We report the case of a 43-year-old woman with adult Wilms' tumor. Imaging studies confirmed the presence of a 25 x 20 x 12 cm mass in the left kidney. A radical transabdominal nephrectomy was performed. Histological diagnosis was adult Wilms' tumor. Postoperative chemotherapy was offered to the patient who remains disease-free 67 months postoperatively. There are a few reported cases of this entity and till today the best treatment options and the prognosis remain unclear. PMID- 17268907 TI - Condylomata acuminata of external urethral meatus causing infravesical obstruction. AB - Condyloma acuminata is one of the most common virally transmitted diseases. The most common sites for condyloma in males are the balanopreputial sulcus, frenulum and the glans' mucosa. Condylomata in the urethra is rarely seen occur and most often situated in the distal part of the urethra. A 24-year-male admitted to our clinic with complaint of papillary lesion at the urethral meatus and urinary retention. Physical examination revealed that multiple papillary lesions along the anterior urethra until 1 cm distance from the urethral meatus. Under the clinical diagnosis of condyloma acuminata, he was treated conservatively with radical local excision of the lesion and condyloma acuminatum was verified by histopathological examination. Four months after surgery, there has been no local or remote recurrence. PMID- 17268908 TI - The role of stenting in relieving loin pain following ureteroscopic stone therapy for persisting renal colic with hydronephrosis. AB - OBJECTIVE: To prospectively define the role of the double J-stent placement following ureteroscopic stone therapy in providing a pain-free postoperative period for patients with persisting loin pain and documented hydronphrosis. MATERIAL AND METHODS: The study cohort consisted of 27 patients (mean age: 38.59 years; range: 22-60 years) who had undergone ureteroscopic intervention due to ureteral stone. All of the patients reported loin pain which did not respond to medical therapy associated with various degrees of hydronephrosis documented by ultrasound and/or an excretory urogram. The patients were randomized to either a stented (18 patients) or stentless (nine patients) group following semirigid ureteroscopy (7.5/12 Fr) for the treatment of ureteral calculi (pneumatic lithotripsy). The mean diameter of the stones was 7.7 mm (range: 3-13 mm). Intra operative balloon ureter orifice dilatation was routinely performed. All patients were evaluated between 0 and 6 days postoperative for loin pain and lower urinary tract symptoms. RESULTS: Nine patients had loin pain in the first few days following the operation and were in need of intramuscular and/or intravenous analgesics. Of these, four were stented patients (4/18; 22.2%) and five were stentless patients (5/9; 55.5%). Lower urinary tract symptoms were not clinically significant and did not affect the quality of life in terms of loin pain, with the exception of one patient in whom the stent had dropped into the bladder. CONCLUSION: We believe that stenting in patients with documented hydronephrosis manifesting in persisting renal colic is recommended. As ureteroscopic therapy may aggregate the edema of ureter mucosa, double J-stent placement may play an important role in offering patients a postoperative period free of loin discomfort. However, further prospective trials should be designed to evaluate the criteria for stentless ureterorenoscopy. PMID- 17268909 TI - Malignant pheochromocytoma with IVC thrombus. AB - A 61-year-old man presented with feeling of bloating, remarkable sweating, and body weight loss. We diagnosed right pheochromocytoma with inferior vena cava (IVC) thrombus by some plasma and urine catecholamine and their metabolites data and imaging findings. The patient underwent right adrenalectomy and IVC thrombectomy without use of cardiopulmonary bypass. Pathological finding showed potentially malignant pheochromocytoma. After operation, his subjective symptom disappeared, and abnormal plasma and urine catecholamine and their metabolites data fell to normal range. It is very important to get preoperative information of the exact location of tumor thrombus for the safe surgical management of pheochromocytoma with IVC thrombus. Magnetic resonance imaging (MRI) and ultrasound imaging more useful for diagnosis of the exact location of IVC thrombus. PMID- 17268910 TI - Asymptomatic spontaneous migration of double pigtail ureteral stent outside the ureter. AB - We report a case of asymptomatic spontaneous migration outside the ureter of a double pigtail ureteral stent. This previously undescribed complication confirms the need for regular follow-up of patients with indwelling stents. PMID- 17268911 TI - Nephrogenic adenoma of the ureter: case report. AB - Nephrogenic adenoma is a rare metaplastic benign lesion of urothelium in response to genitourinary tract procedures, chronic infection, trauma, urinary calculi and immunosuppressive therapy after renal transplantation. It has been reported to occur throughout the urinary tract especially, in the urinary bladder. We report a case of nephrogenic adenoma arising from the lower end of the right ureter with clinical and radiological features suspicious of carcinoma. PMID- 17268912 TI - Case report: good prognosis in leiomyosarcoma of the kidney. AB - Sarcomas represent 1-2% of all malignant renal tumors in adults, with an incidence that increases with advancing age. Renal sarcoma is less common, but more lethal than sarcoma of any other genitourinary site. The common signs and symptoms associated with renal sarcoma in adults include palpable mass, abdominal or flank pain and hematuria similar to those seen with large, rapidly growing renal cell carcinomas. Usually, radical nephrectomy remains the treatment of choice for these tumors, which exhibits an aggressive biological behavior and an unfavorable prognosis. We describe an unusual case of renal leiomyosarcoma that underwent nephron sparing surgery, in a 55-year-old white woman, who had a renal mass for 3 years. The size of the renal mass did not change during this period and no distant metastasis occurred. The patient is still alive without any symptoms of relapse. PMID- 17268913 TI - Case report: subcutaneous metastasis from small cell carcinoma of the prostate. AB - Pure primary small cell carcinoma of the prostate (SCCP) is an extremely rare entity. Natural history of this tumor is similar to that of the bronchogenic small cell carcinoma. Several theories of histogenesis have been proposed. Most widely accepted view is that SCCP arises from pluripotent stem cells of the prostate, which have the ability to differentiate into either epithelial or neuroendocrine type carcinomas. SCCP has an aggressive course, and a majority of patients have distant metastasis at presentation. Since it is a rare entity, no standard treatment regimen has been established. A case of primary pure SCCP with multiple subcutaneous metastases is presented. PMID- 17268914 TI - Contrast induced obstructive anuria in uretero-pelvic junction obstruction secondary to a crossing vessel in a solitary kidney. AB - Acute renal dysfunction due to iodinated contrast is usually associated with non oliguric renal failure. We report an unusual occurrence of complete obstructive anuria in a case of uretero-pelvic junction obstruction secondary to an occlusive crossing vessel precipitated by an intravenous urogram. PMID- 17268916 TI - Assessment of lactate dehydrogenase, alkaline phosphatase and aspartate aminotransferase activities in cow's milk as an indicator of subclinical mastitis. AB - This study examined the activities of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) in the milk of lactating Holstein cows in association with subclinical mastitis (SCM). A total of 94 milk samples were collected from 58 lactating dairy cows representing stages of lactation from the second to the tenth week after calving. Those which were classified as positive by California mastitis test (CMT) were deemed to have subclinical mastitis. All the milk samples were skimmed by centrifugation at 10 000g at 0 degrees C and were used for enzyme activities estimations. The mean activities of LDH and ALP were higher in the milk from udders with SCM than in the milk from healthy udders (p < 0.05). There were no significant differences in AST values. The maximum agreement rates between the CMT results and LDH and ALP values were seen at thresholds of > 180 IU/L and > 40 IU/L respectively (kappa values 0.65 and 0.79, respectively). However, the sensitivity of the tests for identifying SCM at these thresholds was higher for ALP (96.4%) than for LDH (68.5%). In this study, LDH and ALP tests were standardized for cow's milk and results showed that only the ALP test was reliable in the early diagnosis of subclinical mastitis. PMID- 17268917 TI - Pesticide residues in rain water from Hisar, India. AB - Presence of pesticide residues was studied in rain water during 2002 employing multi residue analysis method by gas liquid chromatography equipped with ECD and NPD detectors and capillary columns. The presence of pesticide residues in surface aquatic system triggered the investigation of the presence of pesticides in rain water. A total of 13 pesticides were detected in rain water samples. Among the different groups of pesticides, organochlorines were present in the range of 0.041-7.060 ppb with maximum concentration of p,p'-DDT up to 7.060 microg l(-1). Synthetic pyrethroids were present ranging from 0.100 to 1.000 microg l(-1) and organophosphates in the range of 0.050-4.000 microg l(-1) showing maximum contamination with cypermethrin (1.000 microg l(-1)) and monocrotophos (4.000 microg l(-1)) of the respective groups. Almost 80% samples showed the residues above MRL of 0.5 ppb fixed for multi residues and on the basis of single pesticide, 16-50% samples contained residues above the MRL value of 0.1 ppb. PMID- 17268918 TI - Distribution and sources of polycyclic aromatic hydrocarbons in Wuhan section of the Yangtze River, China. AB - Polycyclic aromatic hydrocarbons (PAHs) are important organic contaminants with great significance for China, where coal burning is the main source of energy. In this study, concentrations, distribution between different phases, possible sources and eco-toxicological effect of PAHs of the Yangtze River were assessed. PAHs in water, suspended particulate matters (SPM) and sediment samples at seven main river sites, 23 tributary and lake sites of the Yangtze River at the Wuhan section were analyzed. The total concentrations of PAHs in the studied area ranged from 0.242 to 6.235 microg/l in waters and from 31 to 4,812 microg/kg in sediment. The average concentration of PAHs in SPM was 4,677 microg/kg, higher than that in sediment. Benzo(a)pyrene was detected only at two stations, but the concentrations were above drinking water standard. The PAHs level of the Yangtze River was similar to that of some other rivers in China but higher than some rivers in foreign countries. There existed a positive relationship between PAHs concentrations and the TOC contents in sediment. The ratio of specific PAHs indicated that PAHs mainly came from combustion process, such as coal and wood burning. PAHs may cause potential toxic effect but will not cause acute biological effects in sedimentary environment of the Wuhan section of the Yangtze River. PMID- 17268919 TI - Sources of PM(10) and PM (2.5) in Cairo's ambient air. AB - A source attribution study was performed to assess the contributions of specific pollutant source types to the observed particulate matter (PM) levels in the greater Cairo Area using the chemical mass balance (CMB) receptor model. Three intensive ambient monitoring studies were carried out during the period of February 21-March 3, 1999, October 27-November 27, 1999, and June 8-June 26, 2002. PM(10), PM(2.5), and polycyclic aromatic hydrocarbons (PAHs) were measured on a 24-h basis at six sampling stations during each of the intensive periods. The six intensive measurement sites represented background levels, mobile source impacts, industrial impacts, and residential exposure. Major contributors to PM(10) included geological material, mobile source emissions, and open burning. PM(2.5) tended to be dominated by mobile source emissions, open burning, and secondary species. This paper presents the results of the PM(10) and PM(2.5), source contribution estimates. PMID- 17268923 TI - A comparison between two moss species used as transplants for airborne trace element biomonitoring in NE Italy. AB - Transplants of the mosses Hypnum cupressiforme and Pseudoscleropodium purum used as active biomonitors of airborne trace elements were compared in a survey carried out at Trieste (NE Italy). Twelve elements were considered: Al, As, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Ti, V, Zn. Water-washed materials of H. cupressiforme and P. purum, collected in a remote area to prepare transplants, showed comparable content of all elements, excluding Pb. Transplants of P. purum showed a significantly higher accumulation of Al, Fe, Pb and Ti; higher levels of Cu and V were accumulated in H. cupressiforme. Losses of some elements occurred in some samples of both species; the most consistent losses regarded Cr and Mn. Accumulation data of Al, As, Cd, Hg, Zn found in the two transplanted sets were not correlated. Differences in element uptake in the two mosses are likely to depend mainly on morphology, and probably on the different forms of emission and deposition types of the elements. The two mosses showed an overall accordance in discriminating sites highly and scarcely affected by trace element depositions, although they accumulated some elements, in particular Hg and Zn, in different ways. P. purum proved to be a better accumulator than H. cupressiforme, showing similar or higher accumulation and lower loss of almost all elements, especially those related to particulate, dry depositions; H. cupressiforme could be effective in detecting large-scale patterns, related to wet depositions. These results indicate that these mosses cannot be used interchangeably for monitoring particular elements, and are able to provide complementary information on different, local and long-range deposition patterns. PMID- 17268920 TI - Effective long-term ecological monitoring using spatially and temporally nested sampling. AB - Effective environmental management requires documentation of ecosystem status and changes to that status. Without long-term data, short-term natural variability can mask chronic and/or cumulative impacts, often until critical levels are reached. However, a trade-off generally occurs between sampling in space and time. This study analyses a spatially and temporally nested long-term (12 years) monitoring programme conducted on benthic macrofauna in a large harbour. Sampling was carried out at six sites for 5.5 years, after which only two sites were sampled for the next 5 years. After this period, all six sites were sampled for another 2 years. While ecology is frequently thought of being highly variable, this design was able to detect trends, and cycles, in abundance, with only around 10% of species at each site exhibiting unpredictable temporal variability. Sites exhibiting similar trends in the abundance of a species over the 12.5-year period were generally spatially contiguous, and the spatial scale of change could be assessed. Continuous sampling at two sites identified whether changes in unsampled sites were related to long-term cycles. Moreover, this sampling provided a long-term background of temporal fluctuations against which to assess the ecological significance of observed changes. PMID- 17268924 TI - Monitoring of aerial pollutants emitted from Swine houses in Korea. AB - This on-site survey study was performed to determine the concentrations and emissions of aerial contaminants in the different types of swine houses in Korea and then to present beneficial information available for Korean pig producers to manage optimal air quality in swine house. The swine houses investigated in this research were selected based on three criteria; manure removal system, ventilation mode and growth stage of swine. Mean concentrations of aerial pollutants in swine houses were 8 ppm for ammonia, 300 ppb for hydrogen sulfide, 2 mg m(-3) for total dust, 0.6 mg m(-3) for respirable dust, 4 log(cfu m(-3)) for total airborne bacteria and 3 log(cfu m(-3)) for total airborne fungi, respectively. Mean emissions based on pig (liveweight; 75 kg) and area (m(2)) were 250 and 340 mg h(-1) for ammonia, 40 and 50 mg h(-1) for hydrogen sulfide, 40 and 50 mg h(-1) for total dust, 10 and 15 mg h(-1) for respirable dust, 1.0 and 1.3 log(cfu) h(-1) for total airborne bacteria and 0.7 and 1.0 log(cfu) h(-1) for total airborne fungi, respectively. In general concentrations and emissions of gases were relatively higher in the swine houses managed with deep-pit manure system with slats and mechanical ventilation mode than the different swine housing types whereas those of particulates and bioaerosol were highest in the naturally ventilated swine houses with deep-litter bed system. PMID- 17268925 TI - Monitoring and assessment of persistent organochlorine residues in sediments from the Daliaohe River watershed, northeast of China. AB - Surface sediment samples from 12 sites of the three selected rivers in Daliaohe River watershed (Hunhe River, Taizihe River and Daliaohe River) were analyzed with the objective of establishing sources and hazard of the organochlorinae pesticides (OCPs) and polychlorinated biphenyl (PCBs) in surface sediments. The total concentrations of OCPs varied from 3.06 to 23.24 ng g(-1). SigmaHCH (alpha HCH, beta-HCH, delta-HCH, gamma-HCH), SigmaDDT (p, p'-DDE, p, p'-DDD, o, p'-DDT, p, p'-DDT) and SigmaCyclodiene (Heptachlor, Aldrin, Heptachlor epoxide, Dieldrin, Endrin) ranged from 1.86 to 21.48, 0.5 to 2.81 and 0.56 to 1.53 ng g(-1), respectively. Results of OCPs also illustrate that the most dominant pollutants among the OCPs was SigmaHCH, and gamma-HCH was the most dominant isomer in HCH, which was evidence of recent input of lindane. It possibly came from the runoff of polluted soils and long-scale transportation. Total PCB concentrations ranged between 1.88 and 16.88 ng g(-1). The peak concentrations of PCBs were found in sediments from station T5 and D3, which are in the vicinity of industrial areas and ferry, respectively. These data show a moderate level of OCPs and PCBs contaminations compared to that in other countries. PMID- 17268926 TI - The SF36 Version 2: critical analyses of population weights, scoring algorithms and population norms. AB - BACKGROUND: The SF36 Version 2 (SF36V2) is a revision of the SF36 Version 1, and is a widely used health status measure. It is important that guidelines for interpreting scores are available. METHOD: A population sample of Australians (n = 3015) weighted to achieve representativeness was administered the SF36V2. Comparisons between published US weights and sample derived weights were made, and Australian population norms computed and presented. MAJOR FINDINGS: Significant differences were observed on 7/8 scales and on the mental health summary scale. Possible causes of these findings may include different sampling and data collection procedures, demographic characteristics, differences in data collection time (1998 vs. 2004), differences in health status or differences in cultural perception of the meaning of health. Australian population norms by age cohort, gender and health status are reported by T-score as recommended by the instrument developers. Additionally, the proportions of cases within T-score deciles are presented and show there are important data distribution issues. PRINCIPAL CONCLUSIONS: The procedures reported here may be used by other researchers where local effects are suspected. The population norms presented may be of interest. There are statistical artefacts associated with T-scores that have implications for how SF36V2 data are analysed and interpreted. PMID- 17268927 TI - Documenting the rationale and psychometric characteristics of patient reported outcomes for labeling and promotional claims: the PRO Evidence Dossier. AB - The Food and Drug Administration (FDA) and European Medicines Agency (EMEA) are willing to consider including information on patient reported outcomes (PROs) in product labeling and advertising. Pharmaceutical industry researchers must provide sufficient evidence supporting PRO benefit before an approval may be granted. This report describes the purpose and content of a PRO Evidence Dossier, which consists of important information supporting PRO claims. The dossier should be completed by pharmaceutical industry or other researchers to document the planning of the PRO assessment strategy, psychometric evidence, desired target labeling statements, and the clinical trial evidence of PRO benefits. The systematic reporting and documentation of information on the rationale for including PROs, rationale for the selection of specific PRO instruments, evidence on the psychometric qualities of the PRO measures, and guidelines for interpreting PRO findings will facilitate achieving a PRO labeling or promotional claim. Combining all the relevant information into a single document will facilitate the review and evaluation process for clinical and regulatory reviewers. The PRO Evidence Dossier may also be helpful to industry and academic researchers in identifying further information that will need to be developed to support the clinical development program and the PRO endpoints. PMID- 17268928 TI - Twelve years' experience with the Patient Generated Index (PGI) of quality of life: a graded structured review. AB - The Patient Generated Index (PGI) is an individualised quality of life (QoL) measure that has been in use since 1994. Various adaptations have been made to suit a variety of client groups. The PGI's psychometric properties have been studied but their review is necessary to inform instrument choice. This article provides a structured review, using grading criteria adapted from those developed to aid outcome measure selection for use with older people. These criteria grade quality of evidence and strength of findings for psychometric validity, providing a useful model for future reviews. All published articles providing data addressing validity, reliability and/or responsiveness were included in the review. Eighteen relevant articles were identified and analysed using the grading criteria. Variable results and quality of investigation were seen. Generally the measure was found to be adequately reliable for group comparisons. The PGI appeared valid but evidence for responsiveness was unclear. Those versions of the measure using fewer points in their Likert scales may have higher reliability. Cognitions involved in QoL judgements remain little understood and investigations of psychometric properties may be enhanced by examination of appraisal processes. PMID- 17268929 TI - Health-related quality of life in HIV-1-infected patients on HAART: a five-years longitudinal analysis accounting for dropout in the APROCO-COPILOTE cohort (ANRS CO-8). AB - BACKGROUND: The long-term efficacy of Highly Active Antiretroviral Therapies (HAART) has enlightened the crucial role of health-related quality of life (HRQL) among HIV-infected patients. However, any analysis of such extensive longitudinal data necessitates a suitable handling of dropout which may correlate with patients' health status. METHODS: We analysed the HRQL evolution over 5 years for 1,000 patients initiating a protease inhibitor (PI)-containing therapy, using MOS SF-36 physical (PCS) and mental (MCS) scores. In parallel with a classical separate random effects model, we used a joint parameter-dependent selection model to account for non-ignorable dropout. RESULTS: HRQL evolved according to a two-phase pattern, characterized by an initial improvement during the year following HAART initiation and a relative stabilization thereafter. Immunodepression and self-reported side effects were found to be negative predictors of both PCS and MCS scores. Hepatitis C virus coinfection and AIDS clinical stage were found to affect physical HRQL. Results were not significantly altered when accounting for dropout. CONCLUSION: Such results, obtained on a large sample of HIV-infected patients with extensive follow-up, underline the need for a regular monitoring of patients' immunological status and for a better management of their experience with hepatitis C and HAART. PMID- 17268930 TI - Psychological acceptance and quality of life in the elderly. AB - Many changes occur as people enter old age (e.g., declining productivity), and these changes may at times decrease quality of life. Do some people maintain high subjective quality of life despite these changes? This study investigated the influence of psychological acceptance (PA) on quality of life in a sample of 187 elderly from a home nursing service, a retirement village and various community groups. Average age was 78 years old with a range from 65 to 96. We administered a measure of psychological acceptance and The Comprehensive Quality of Life Scale (COMQol). As hypothesised, people higher in PA also had higher quality of life in the areas of health, safety, community participation and emotional well-being. In addition, individuals high in PA had less adverse psychological reactions to decreasing productivity. Interventions that increase PA may lead to improved quality of life and resilience amongst the elderly. PMID- 17268931 TI - What drives older women's perceptions of health-related quality of life? AB - BACKGROUND: Age-related differences in the way ratings of health related quality of life (HRQL) are produced are poorly understood, especially for older women. OBJECTIVE: To examine age differences in critical dimensions of HRQL among older women using structural equation modelling. We hypothesized that physical, mental and social health domains would exert weaker total effects on HRQL among older middle-aged versus much older women. METHODS: A model of HRQL was developed and confirmatory factor analysis (CFA) was used to test the structure of the model across two samples of community-dwelling women aged 55 years and older. The relationships between the constructs and the relative magnitude of direct and indirect effects on HRQL were evaluated in a series of path models, with women younger and older than age 70 tested separately. RESULTS: The CFA model of HRQL showed excellent fit in both the national and verification samples (RMSEA 0.04 and 0.02 respectively). In the path model, the total effects of physical, mental and social health on general perceptions of HRQL were greater and more significant in middle-aged versus older women (beta coefficients 0.810, 0.277, 0.266, all P < 0.05 versus, 0.700, 0.189, and 0.057, P < 0.05 for physical and mental health only respectively). CONCLUSION: This HRQL model suggests different opportunities for intervention among older women to improve the outcomes along the path to HRQL. PMID- 17268932 TI - Are persons with physical disabilities who participate in society healthier and happier? Structural equation modelling of objective participation and subjective well-being. AB - In many countries, governments pursue a policy of offering persons with disabilities greater opportunities for participation in society, based on the assumption that this will also improve their subjective well-being. Currently, however, it is not known whether this assumption is valid. In this study we relate the objective participation and the subjective well-being aspects of both disabled and non-disabled persons to an array of social and health-related determinants. Linear structural equation modelling of data of a sample selection of the Dutch population is analysed. The sample size is 5,826, including 642 respondents with physical disabilities. In terms of objective participation, the persons with disabilities are at a greater disadvantage as regards labour participation than is the case for social and cultural participation. When it comes to subjective well-being, we find that the persons with disabilities are more likely to lag behind in perceived physical health than in mental health and happiness. In a multivariate model relating objective participation to subjective health and happiness, correlations are much weaker than expected. It is striking to find that participation, perceived health and happiness are much less closely related than is often assumed. Their determinants differ widely in nature and strength. The empirical model leads to rejection of the hypothesis that higher participation by the persons with disabilities is associated with higher subjective well-being. PMID- 17268933 TI - The role of coping strategies in quality of life of adolescents with asthma. AB - This study aimed to determine which coping strategies are associated with better quality of life (QOL) in adolescents with asthma. Furthermore, because coping can mediate the effects of health stressors on QOL, this study also examined the indirect effect of asthma severity on QOL via coping. Between January and May 2003, 553 Dutch adolescents with asthma (aged 12-16 years) completed questionnaires assessing coping strategies, symptom severity, overall QOL and positive QOL domain (positive effects of asthma domain). The relations between symptom severity, coping strategies and QOL were tested with structural equation modelling (SEM). Symptom severity affected overall and positive QOL, both directly and indirectly via coping. The coping strategies restricted lifestyle and worrying about asthma were associated with poorer overall QOL. The use of the coping strategies restricted lifestyle, positive reappraisal, and information seeking was related to increased scores on the positive QOL domain, whereas hiding asthma was related to lower scores on the positive QOL domain. The findings of this study suggest that coping mediates the effect of symptoms of asthma on QOL among adolescents with asthma. Several suggestions for interventions to improve asthma-specific QOL are discussed. PMID- 17268934 TI - The Affectometer 2: a measure of positive mental health in UK populations. AB - OBJECTIVE: To validate Affectometer 2 for use in the UK, derive population norms and assess its potential for monitoring positive mental health. METHODS: 722 adults aged 16-74 living in Scotland completed Affectometer 2 and the General Health Questionnaire (GHQ) and provided data on socio-economic factors known to be associated with mental health status. Principal component analysis was used to explore the underlying structure of Affectometer 2. Internal reliability was tested using Cronbach's alpha. Construct validity was tested by comparing associations between Affectometer 2 scores and socio-economic factors with expected performance from other surveys and with the GHQ. RESULTS: 89% of participants completed Affectometer 2 suggesting a high level of public acceptability. Both total scale and subscales showed a high level of internal consistency (0.944). Correlations between Affectometer 2 score and key socio economic variables were consistent with the findings of other population mental health surveys. Correlation with the GHQ was moderate (0.60). Affectometer 2 did not show a ceiling effect in this general population sample. Principal component analysis provided some evidence consistent with a single underlying construct, although this needs further testing. CONCLUSIONS: Affectometer 2 met accepted criteria for validity and reliability in this representative UK population and demonstrated potential for use in monitoring positive mental health. The results provide support for the development of a shortened version of the scale which would be advantageous for population surveys. PMID- 17268935 TI - Burden of restless legs syndrome on health-related quality of life. AB - OBJECTIVE: To quantify the total and unique burden of Restless Legs Syndrome (RLS) on patient-reported health-related quality of life (HRQoL). METHODS: The disease burden that RLS places on HRQoL was estimated by comparing Short-Form (SF 36) scores between individuals with RLS and several patient and general populations in the US. Regression methods were applied to estimate SF-36 normative values from the general population sample and statistically adjust them to match age, gender and disease comorbidity characteristics of the RLS sample. Significance tests were then used to compare the means across samples. RESULTS: All SF-36 measures were significantly below adjusted US general population norms. Five of the eight scales (physical functioning, role physical, bodily pain, general health, vitality) were below US norms by 0.8 or more standard deviations (SD), while the remaining three (social functioning, role emotional, mental health) were 0.5 SD below norm. The burden of RLS was greater on physical than on mental/emotional HRQoL (physical and mental summary scores were 1.08 and 0.40 SD below norm, respectively), and greater than that observed for type-2 diabetes. CONCLUSION: After controlling for the impact of age, gender, and disease comorbidity, RLS was associated with unique burden on both physical and mental aspects of HRQoL. PMID- 17268936 TI - Pharmacovigilance and pharmacoepidemiology of drugs in a Mexican pediatric hospital. A proposed guide. AB - We describe the procedures of pharmacovigilance (PV) and pharmacoepidemiology (PE) of drugs in a pediatric hospital. These activities contribute to the detection and registration of adverse drug reactions and to determine the patterns of drug prescription among children attended at the hospital. The PV activities show that there is a relation between an increase in incidence of adverse drug reactions and the prescription of a larger number of drugs. The PE activities reveal that antibiotics are the most frequently prescribed drugs and next are drugs used for gastrointestinal diseases. Since PV and PE activities were initiated at our hospital, they have contributed to a more adequate use of drugs in children. As a conclusion of these activities, it could be that if the PE of a hospital is known, drug consumption can be optimally planned. PV and PE demonstrate that, if polytherapy is not necessary, it must be avoided. Finally, the present guide can be adopted to initiate PV and PE at a hospital. PMID- 17268938 TI - Pharmacy interns on the ward--a pilot study. AB - OBJECTIVE: To assess the feasibility and impact of the activities of pharmacy interns on German hospital wards as well as the acceptance of their activities by medical and pharmaceutical staff. METHOD: The project was carried out for 36 months in six hospitals on different wards. Seventeen interns spent three months first in the pharmacy followed by another three months in the wards. Information about their tasks on different wards was obtained through reporting by interns on a standardized data collection form. Questionnaires regarding acceptance and impact of pharmacy interns were answered by medical and pharmaceutical staff. RESULTS: After having adjusted to their tasks, the interns investigated and developed solutions for structural and process-related slacks in the handling of medicines in the wards. They focused on drug information, on the detection and prevention of medication and documentation errors and storage of medicines in the wards. One hundred and forty six questionnaires regarding acceptance, impact and possible tasks of the interns were answered. Ninety percent of the surveyed medical staff considered the work of the interns as useful and 89% were in favour of permanent interns in the wards. The acceptance by pharmaceutical staff was slightly lower. CONCLUSION: This pilot study represents a landmark for the implementation of clinical pharmacy in daily practice especially on medical wards in Germany. Working in wards offers interns a possibility to extend their knowledge and skills. The project demonstrates that pharmacy interns can play an important role in drug safety in hospital wards. The acceptance by physicians and nurses is high. The majority of them requested the continuation of the project. PMID- 17268937 TI - The influence of the Pharmaceutical Benefits Scheme (PBS) on inappropriate prescribing in Australian nursing homes. AB - OBJECTIVES: To determine the prevalence of inappropriate prescribing, defined by applying modified Beers' criteria, and to examine the influence of the Pharmaceutical Benefits Scheme (PBS), Australia's national scheme for subsidising medicines, on inappropriate prescribing. METHODS: Cross-sectional survey of nursing home records, including 7-days data from medication charts. SETTING: Fiveteen randomly selected nursing homes (998 residents) in Southeast Queensland and Northern New South Wales, Australia. MAIN OUTCOME MEASURES: The prevalence of inappropriate prescribing as defined by modified Beers' criteria and its correlation with PBS restrictions. RESULTS: 18.5% of residents were ordered one or more inappropriate medications, and 1.5% of residents were ordered two or more. The level of PBS restriction and the percentage of residents ordered a medication were highly correlated (p = -0.87, P < 0.001). Medications in Beers' criteria that were not listed (subsidised) on the PBS were not ordered for any resident. PBS medicines with subsidies restricted to certain populations or indications were ordered for 0% to 0.1% of residents. Dextropropoxyphene, diazepam, amitriptyline and methyldopa were the only medications in Beers' criteria prescribed to more than 0.5% of residents. Dextropropoxyphene was only subsidised for war veterans, with a caution warning of its potential to cause drug dependence, while diazepam, amitriptyline and methyldopa were listed on the PBS without any subsidy restrictions. CONCLUSION: Increases in the level of PBS restriction were associated with decreases in the prevalence of inappropriate prescribing, The targeting of drug subsidies to reduce inappropriate prescribing warrants further investigation. PMID- 17268939 TI - The role of the pharmacist-voices from nine African countries. AB - OBJECTIVE: To explore views on pharmacy practice in Africa as perceived by pharmacists from several African countries. METHOD AND SETTING: Data was collected using pre-tested semi-structured interview guides. A total of 15 pharmacists from nine African countries were interviewed. The analysis used a phenomenographic approach where categorisation with regard to differences in expressed perceptions of the pharmacist's role was made. MAIN OUTCOME: Perceptions on pharmacy practice in Africa as expressed by pharmacists from nine African countries. RESULTS: Four qualitatively different ways of perceiving the pharmacist's role were identified and sorted into subcategories under the two main categories A and B as follows A. Pharmaceutical information provider with the sub-categories: A1. The satisfied dispenser, and A2. The dissatisfied dispenser; and B. Health care provider, with the sub-categories: B1. The health care team member, and B2. The lifesaver. In category A, the pharmacist is described foremost as a provider of pharmaceuticals and information with a distinction being made with regard to whether the interviewees expressed dissatisfaction with their situation or not. In category B, the pharmacist was described as a provider of health care and two different approaches to this were found. CONCLUSION: The study describes different ways of perceiving the role of the pharmacist in nine African countries. It offers an insight into the situation of the African pharmacist that can be used as a starting point for further discussion and research on the development of pharmacy practice and for the creation and implementation of national Good Pharmacy Practice (GPP) guidelines. PMID- 17268940 TI - Assessing a pharmacist-run anaemia educational programme for patients with chronic renal insufficiency. AB - OBJECTIVE: Assessment of a pharmacist-run anaemia educational programme for patients with chronic renal insufficiency. SETTING: Nephrology Department, Grenoble Hospital, France. METHOD: A 12-week prospective study, using a before after intervention design. Included in the study were predialysis outpatients with a haemoglobin level < 10 g/dl, de novo EPO prescription; judged qualified by the nephrologist for self-injections; accepting self-injections. The intervention was a single one-hour individual session between the pharmacist and the patient to target (1) medical and therapeutic information; (2) information on the device, a pen used with a cartridge of beta epoietin; (3) training with the pen; and (4) self-injection of the first dose by the patient, in front of the pharmacist. Main outcome measures were knowledge (7-item questionnaire); handling skills (observation) and Quality of Life (1 Likert scale on apprehension towards self injections and 3 Linear Analog Scales on energy, daily activities, and general well-being); compliance (self-report on self-administered injections) and haemoglobin level. RESULTS: Ten patients were followed for 3 months after intervention. The evolution of the knowledge was positive but not statistically significant after the programme (80% of good answers before; 93% 3 months later). Concerning the patients' skills, difficulties with the pen were important at inclusion, (1) to reset the pen into zero position (2.8 tries/patient +/- 1.8); (2) to insert a new cartridge (1.9 +/- 1.1); and (3) to take air out of the cartridge (2.3 +/- 1.2). After the session, results were satisfactory, since 3 months later, all patients were still on self-injections. QoL improved significantly over the study period respectively on energy, daily activities, and general well-being. The mean level of compliance remained above 90% at 3 months for 8 out of 10 patients. Patients reached the haemoglobin target value of 11 g/dl during the second month of treatment. CONCLUSION: A tailored educational programme conducted by a pharmacist is beneficial for anaemia patients with chronic renal insufficiency. The programme seems to result in a high level of compliance, leading to an optimal haemoglobin level within two months. PMID- 17268941 TI - Refill non-adherence to repeat prescriptions leads to treatment gaps or to high extra costs. AB - OBJECTIVE: To determine the nature and extent of undersupply and the economic consequences of oversupply of medication among non-adherent patients. METHODS: This study used copies of repeat prescriptions (= multiple dispensations), collected during 1 week in 2002 at 16 Swedish community pharmacies. For patients with a refill adherence below 80%, treatment gaps were defined as the number of days they had no drug available. The cost of drug oversupply (i.e., refill adherence > 120%) was calculated from the prices of the drug packages dispensed. RESULTS: The number of collected repeat prescriptions was 3,636. The median of treatment gaps among patients with a refill adherence below 80% was 53 days per 90-100 days treatment period and the corresponding median for oversupply was 40 days. The cost of oversupply for exempt patients (i.e., patients who have paid 1,800 SEK (Euro 196; US$ 243) per year for medicines) was 32,000 SEK (Euro 3,500; US$ 4,300) higher than for non-exempt patients. An extrapolation to all Sweden indicates that exemption from charges leads to an additional oversupply of about 142 million SEK (Euro 15 million; US$ 19 million) per year above that of non exempt patients. CONCLUSION: Both undersupply and oversupply of prescribed medicines are common in Sweden. Patients with a refill adherence below 80% seem to have less than half of the prescribed treatment available. Oversupply or drug stockpiling occurs more frequently among exempt than among non-exempt patients, and this oversupply leads to high unnecessary costs. PMID- 17268942 TI - Consumer behaviour in the waiting area. AB - OBJECTIVE OF THE STUDY: To determine consumer behaviour in the pharmacy waiting area. METHOD: The applied methods for data-collection were direct observations. Three Dutch community pharmacies were selected for the study. The topics in the observation list were based on available services at each waiting area (brochures, books, illuminated new trailer, children's play area, etc.). Per patient each activity was registered, and at each pharmacy the behaviour was studied for 2 weeks. RESULTS: Most patients only waited during the waiting time at the studied pharmacies. Few consumers obtained written information during their wait. CONCLUSION: The waiting area may have latent possibilities to expand the information function of the pharmacy and combine this with other activities that distract the consumer from the wait. Transdisciplinary research, combining knowledge from pharmacy practice research with consumer research, has been a useful approach to add information on queueing behaviour of consumers. PMID- 17268943 TI - The effects of introducing a clinical pharmacist on orthopaedic wards in Denmark. AB - OBJECTIVE: To assess the effects and cost effects of introducing clinical pharmacists on hospital wards. METHODS: Comparative prospective study on four orthopaedic surgical wards in two hospitals. The primary effect variables were 10 target areas widely considered to be indicators of good prescription practice. Prescriptions not following good practice in these intervention areas were defined as "sub-optimal prescriptions," and then discussed between a physician and a clinical pharmacist. The primary parameter was the difference in the number of days with a sub-optimal prescription (Mann-Whitney test). RESULTS: On an average 20% of all the patients had a sub-optimal prescription. Of these, 70% were changed by the physician after intervention by the clinical pharmacist. There was a statistically significant difference in the duration of days in treatment with a sub-optimal prescription. Where sub-optimal prescriptions were changed, 43% resulted in cost reductions. The reductions achieved could cover 47% of the costs of clinical pharmacy service. CONCLUSION: Clinical pharmacy services offered to four orthopaedic surgical wards resulted in reduction of sub-optimal prescriptions. Every time the pharmacist screened seven patients one sub-optimal prescription was found and adjusted. The reduction in medicine costs due to adjusted sub-optimal prescriptions could not cover the whole cost of clinical pharmacy service. PMID- 17268944 TI - Tibial geometry is associated with failure load ex vivo: a MRI, pQCT and DXA study. AB - We studied the relations between bone geometry and density and the mechanical properties of human cadaveric tibiae. Bone geometry, assessed by MRI and pQCT, and bone density, assessed by DXA, were significantly associated with bone's mechanical properties. However, cortical density assessed by pQCT was not associated with mechanical properties. INTRODUCTION: The primary objective of this study was to determine the contribution of cross-sectional geometry (by MRI and pQCT) and density (by pQCT and DXA) to mechanical properties of the human cadaveric tibia. METHODS: We assessed 20 human cadaveric tibiae. Bone cross sectional geometry variables (total area, cortical area, and section modulus) were measured with MRI and pQCT. Cortical density and areal BMD were measured with pQCT and DXA, respectively. The specimens were tested to failure in a four point bending apparatus. Coefficients of determination between imaging variables of interest and mechanical properties were determined. RESULTS: Cross-sectional geometry measurements from MRI and pQCT were strongly correlated with bone mechanical properties (r(2) range from 0.55 to 0.85). Bone cross-sectional geometry measured by MRI explained a proportion of variance in mechanical properties similar to that explained by pQCT bone cross-sectional geometry measurements and DXA measurements. CONCLUSIONS: We found that there was a close association between geometry and mechanical properties regardless of the imaging modality (MRI or pQCT) used. PMID- 17268945 TI - Projected prevalence of US adults with self-reported doctor-diagnosed arthritis, 2005 to 2050. AB - Using population-based survey data from the 2003 Behavioral Risk Factor Surveillance Survey (BRFSS), we estimated the population prevalence of self reported, doctor-diagnosed arthritis in the US from 2005 to 2050. Projected arthritis-prevalence data were estimated in 5-year increments along sex- and age specific categories by multiplying the 2003 BRFSS arthritis prevalence data by the sex-stratified US Census projections. During this 45-year period, we estimate that the total number of US adults aged 20 years or older with arthritis will increase from 60 million to 96 million, a 1.6-fold increase. The increase is projected to be greater in those aged 65 years or older (a 2.3-fold increase) than for those aged 20 to 65 (a 1.3-fold increase). Given increases in the prevalence of known arthritis risk factors (e.g., obesity, Hispanic origin) our projections might underestimate the prevalence of arthritis in the coming years. PMID- 17268946 TI - Compliance with a fetal movement chart by high-risk obstetric patients in a Peruvian hospital. AB - We sought to determine the degree of compliance with a novel fetal movement chart (FMC) by high-risk patients versus the standard so-called count-to-10 method. This prospective trial included 1400 high-risk patients. Women with singleton gestations were randomly assigned to use either the count-to-10 chart or a FMC proposed by the Latin American Center for Perinatology (CLAP). Advantages and disadvantages were identified by patients. Compliance with regimens was measured and compared between the two groups. Demographic characteristics were similar. Compliance in the CLAP group (448 of 700) was lower than in the count-to-10 group (638 of 700; 64 versus 91%; P < 0.0001). The main advantage of the count-to-10 chart was lack of interference with daily activities. No intrauterine demises occurred in either group. High-risk patients were more compliant with the standard count-to-10 charting method than with the novel FMC. The count-to-10 method is an easy and inexpensive tool for fetal monitoring and should continue to be used in obstetric practice. PMID- 17268948 TI - [Skin and occupation]. PMID- 17268950 TI - [Palliative medicine content in German-language medical textbooks]. AB - BACKGROUND: There is a need for improved end-of-life care, especially in the light of demographic changes with an increased incidence of cancer. Although medical textbooks are central to the training of medical students and also serve as a reference for more experienced clinicians, only few data exist on the extent to which medical textbooks address end-of-life care. We analysed the quantity and quality of information on end-of-life care given in German textbooks on different medical disciplines. MATERIAL AND METHODS: 26 top-selling German medical textbooks were analysed for the presentation of end-of-life care in chapters that address the 13 most common causes of death worldwide RESULTS: In the 159 chapters analysed for information on traditional topics, like risk factors or early diagnosis (group A), such information was provided in 52% compared with only 9% on end-of-life topics, such as symptom management or manner of death (group B) (p=0.0001). There was no statistically significant difference between the different medical specialities (p=0.22). Line-by-line analysis showed that the phrase death or related terms was mentioned in only 57 of 159 chapters dealing with the most common causes of death worldwide. CONCLUSION: The top-selling German textbooks that were analysed generally offer little helpful information on end-of-life care of patients. PMID- 17268951 TI - [Misleading information on smoking in German medical textbooks]. AB - BACKGROUND AND OBJECTIVE: Smoking is a major risk factor for coronary heart disease and lung cancer. While nicotine causes addiction, heart and lung diseases are caused by other substances contained in tobacco smoke. This study assessed whether these facts are adequately portrayed in German medical textbooks. METHODS: The sections on cardiovascular and lung cancer risk factors in 28 German textbooks of internal medicine, available in two bookstores as well as the library of Gottingen University (Germany), were scanned for the words "smoking" and "nicotine" as risk factors for coronary artery disease and lung cancer. RESULTS: In 12 of the 25 textbooks covering cardiovascular disease, smoking was mentioned as a risk factor for coronary artery disease; another 12 textbooks listed nicotine or nicotine addiction. In one textbook both terms were used. While smoking was referred to in all 21 textbooks that also discussed risk factors for lung cancer, nicotine was not mentioned in this context. CONCLUSION: Many German textbooks of internal medicine contain misleading terms for the health effects of smoking, which may influence the thoughts and possibly also the behaviour of their readers. The use of the words "smoking" and "nicotine" as synonymous within the context of cardiovascular risk factors, suggesting a causal relationship between nicotine and coronary heart disease, is incorrect and should be removed from the specialist medical literature. PMID- 17268952 TI - [A rare cause of dysphagia and bolus obstruction in adults]. AB - HISTORY: An otherwise healthy 20-year-old man was admitted to our hospital with obstruction of the oesophagus by a bolus after eating a chicken meal. These symptoms continued over the past 12 years and required multiple interventions at different hospitals. There was no history of any other previous illness and both the physical examination and routine laboratory tests were unremarkable. INVESTIGATIONS: Esophagogastroduodenoscopy (EGD) revealed segmental circular trachea-like constrictions of the esophagus and two stenoses at 35 cm and 40 cm. Histopathology of several biopsies favored the diagnosis of eosinophilic esophagitis. TREATMENT AND FURTHER COURSE: After initial balloon dilatation and dilatation with a Savary bougie the patient was put on systemic steroids and montelukast (a leukotriene receptor antagonist). The symptoms subsequently disappeared. CONCLUSION: Eosinophilic esophagitis, a unique form of esophageal inflammatory disease, consists of dense eosinophilic infiltration of the epithelium and is associated with various macroscopic findings, such as the rare but striking circular trachea-like constrictions, nodules, plaques and other forms of constriction of the esophagus. Several lines of evidence favor an allergic cause. The leading symptom is recurrent dysphagia after solid foods, sometimes accompanied by heart-burn. Medical treatment consists of topical or systemic administration of steroids and/or montelukast. A history of chronic dysphagia after eating solid food, combined with endoscopic findings atypical for reflux disease is highly suspicious of eosinophilic esophagitis in the differential diagnosis of gastroesophageal reflux disease in adults. PMID- 17268953 TI - [Double opening of the renal arteries and transplantation renal vein stenosis]. PMID- 17268954 TI - [Lactose intolerance: new aspects of an old problem]. PMID- 17268955 TI - [Cardiac resynchronization and atrial fibrillation: possibilities and limitations]. PMID- 17268956 TI - [Drinking water in hospitals: water coolers vs. drinking water systems vs. mineral water in bottles]. PMID- 17268957 TI - Further eudesmane derivatives from verbesina species. AB - The aerial parts of VERBESINA PERSICIFOLIA DC afforded a new eudesmane derivative in addition to known compounds. The roots of V. SUBCORDATA gave also new eudesmane cinnamates in addition to several known ones as well as a 5alpha hydroxybicyclogermacra-1 (10) E, 4 (15)-diene. A reinvestigation of V. VIRGINICA L. gave two new ( Z)-configurated coumarates. Furthermore the structures of some sesquiterpenes are revised. The structures were elucidated by highfield NMR spectroscopy and a few chemical reactions. PMID- 17268958 TI - Cardiac Glycosides from the Leaves of Digitalis cariensis. AB - From the leaves of DIGITALIS CARIENSIS in addition to the known glycosides, three new cardenolides, a major and two minor ones, have been isolated and their structures established as gluco-gitoxigenine-glucomethyloside (gitoxigenine-3- O beta- D-glucosyl-beta- D-glucomethyloside), gitoxigenine-3- O-beta- D-glucosyl beta- D-glucomethylosyl-beta- D-bisdigitoxoside, and gitoxigenine-3- O-beta- D glucosyl-beta- D-glucomethylosyl-beta- D-digitoxide, respectively, by chemical evidence and FAB-MS. Except for the unstable glucolanadoxine, the known major components isolated from the leaves are glucogitoroside, glucoevatromonoside, digitalinum verum, gluco-digitoxigenine-glucomethyloside, glucodigifucoside, and glucogitofucoside. A total of 23 cardenolides present in the leaves in trace amounts were also identified. PMID- 17268959 TI - Isolation and Structure of Neriumol and Nerifol from the Leaves of Nerium odorum. AB - From the fresh, undried, uncrushed leaves of NERIUM ODORUM, two hydroxy acid methyl esters, neriumol and nerifol, have been isolated and their structures established as methyl (7 S,16)-dihydroxyhexadeca-8 Z-enoate and methyl (8,16) dihydroxyhexadecanoate, through chemical and spectroscopic methods. PMID- 17268961 TI - A New Stereoidal Saponin from Polygonatum officinale. AB - Methanol extract of defatted rhizomes of POLYGONATUM OFFICINALE All. yielded a mixture of steroidal saponins. The structures of polyfuroside and odospiroside have been elucidated. PMID- 17268960 TI - New Pseudoguaianolides from Ambrosia maritima. AB - The investigation of the aerial parts of two collections of AMBROSIA MARITIMA afforded in addition to known pseudoguaianolides nine new ones including two nor sesquiterpene lactones and two dimeric lactones. The structures were elucidated by highfield (1)H-NMR spectroscopy. PMID- 17268962 TI - Physalindicanols, New Biogenetic Precursors of C28-Steroidal Lactones from Physalis minima var. indica. AB - The structures of two isomeric C (28)-sterols isolated from PHYSALIS MINIMA Linn. var. INDICA were elucidated as ergosta-5,25-dien-3beta,24zeta,-diol and ergosta 5,24(28)-dien-3beta,25-diol on the basis of detailed spectral analysis. The isolated sterols are regarded as precursors in the elaboration of complex C (28) steroidal lactones, native in this plant and related species. PMID- 17268963 TI - Indole Alkaloids from Trachelospermum jasminoides. AB - The leaves and stems of T. JASMINOIDES have been found to contain indole alkaloids. Five indole alkaloids, coronaridine, voacangine, apparicine, conoflorine, and 19-epi-voacangarine have been isolated. The (13)C-NMR spectra of apparicine and 19-epi-voacangarine are also reported. PMID- 17268964 TI - HPLC of Glycoalkaloids from Solanum sodomaeum. AB - Glycoalkaloids were extracted from plant material of SOLANUM SODOMAEUM L. High performance liquid chromatographic studies indicated that several glycoalkaloids were present. The sugar moiety of the glycoalkaloids consisted of a mixture of glucose, rhamnose, and galactose. Mass spectral analyses showed that all the glycoalkaloids contained solasodine. Solasonine and solamargine were identified and were present at similar concentrations, representing 67% of the total extracted glycoalkaloids. The extraction yield of the glycoalkaloids from plant material, expressed as g glycoalkaloid/100 g wet weight, was highest for ripe fruit (0.83 +/- 0.11), followed by unripe fruit (0.45 +/- 0.08), leaves (0.14 +/- 0.01), and stems (< 0.04) with progressively decreasing yields. Over a twofold difference in glycoalkaloid yield was observed when ripe fruit of two different districts was extracted. PMID- 17268965 TI - Triterpenoid Glycosides from the Roots of Patrinia scabiosaefolia. AB - Four saponins were isolated from the roots of PATRINIA SCABIOSAEFOLIA (Valerianaceae) and identified as 3- O-alpha- L-arabinopyranosylhederagenin 28- O beta- D-glucopyranosyl(1-->6)-beta- D-glucopyranoside ( 2) and its 2'-acetate ( 1) and 3- O-beta- D-glucopyranosyl(1-->3)-alpha- L-rhamnopyranosyl(1-->2)-alpha- L-arabinopyranosyloleanolic acid ( 3) and its 28- O-beta D-glucopyranosyl(1-->6) beta- D-glucopyranoside ( 4). PMID- 17268966 TI - Volatile Constituents of Artemisia vestita Oil1. AB - The essential oil of ARTEMISIA VESTITA (Compositae) was investigated by GLC, NMR, and mass spectrometry. Main constituents are alpha-, beta-, gamma-himachalene, caryophyllene, germacrene D, himachalol, allohimachalol, alpha-, gamma-atlantone, 1,8-cineole, yomogi alcohol, artemisia, and santolina alcohol and their acetates, and the thujones and thujanols. The characteristic oder of the oil is determined by the freshly smelling, 1, 8-cineole and thujone, and by the woody and sweet note of himachalol and atlantone. PMID- 17268967 TI - Acridone Alkaloids and Other Constituents of the Leaves of Atalantia ceylanica. AB - The leaves of ATALANTIA CEYLANICA have yielded four compounds including a novel benzaldehyde derivative, 2,4,5-trimethoxybenzaldehyde ( 1), and two acridone alkaloids: 1,5-dihydroxy-3-methoxy-10-methyl-9(10 H)-acridinone ( 2) and 11 hydroxynoracronycine ( 3), 2 is a new alkaloid and constitutes one half of the dimeric alkaloid atalanine, whilst 3 is one half of ataline. In addition, the leaves were found to contain the pyranoflavone carpachromene ( 4). PMID- 17268968 TI - N-Benzoyl-16-acetylcycloxobuxidine: A New Alkaloid from the Leaves of Buxus papilosa. AB - A new alkaloid, N-benzoyl-16-acetylcycloxobuxidine, has been isolated from the leaves of BUXUS PAPILOSA, to which structure 1 has been assigned. PMID- 17268969 TI - cis- and trans-Neocnidilide; 1H- and 13C-NMR Data of Some Phthalides. AB - The (1)H- and (13)C-NMR spectra of several naturally occurring phthalides are reported; among others, the new natural compound 3,3alpha- CIS-neocnidilide isolated from APIUM GRAVEOLENS L. (and also found to be present in ANETHUM GRAVEOLENS L.). For some compounds, data are compared with previously published data. PMID- 17268970 TI - A method for the quantitative determination of anthraquinones and alkaloids in cell and tissue cultures of cinchona sp. AB - A procedure is described for the extraction of both anthraquinones and alkaloids from tissue culture material of CINCHONA species. Using this extraction method, it is possible to quantitatively determine the two groups of secondary metabolites produced in CINCHONA tissue cultures. PMID- 17268971 TI - Biotransformation of a [14CH3]-2-Methylaminobenzophenone by Plant Cell Cultures. AB - 2-[ (14)C]-Methylamino-2',4'-dimethoxy-6'-hydroxybenzophenone ( 4) was synthesized and administered to RUTA GRAVEOLENS cell suspension cultures. Compound 4 was not incorporated into acridone alkaloids but glucosylated giving 7. This reaction takes place also in cell suspension cultures of ADHATODA VASICA and PEGANUM HARMALA. PMID- 17268972 TI - Clonal propagation of chemically uniform fennel plants through somatic embryoids. AB - Somatic embryoids obtained from cell suspension cultures of fennel in Linsmaier Skoog medium containing 2,4-D and kinetin readily developed into plantlets when plated on a hormone-free agar medium. These plants were transplanted to the field to be tested for the uniformity of the chemically as well as the morphologically important characteristics of fruits. The results of field trials conducted for two years have confirmed that the clonal plants derived from somatic embryoids are remarkably uniform in all the characteristics examined in comparison with the control plants propagated through seeds. It is suggested, therefore, that the quality control of fennel fruits used for spice or medicine could be achieved by means of clonal propagation through somatic embryoids. PMID- 17268973 TI - Changes in the Essential Oil Components during the Development of Fennel Plants from Somatic Embryoids. AB - Quantitative and qualitative changes of essential oils during the development of clonal plants of fennel propagated through somatic embryogenesis were investigated. Although no essential oil could be detected either in cultured cells or in somatic embryoids, monoter-penes such as alpha-phellandrene and alpha pinene were found in radical leaves of regenerated plantlets cultured on a hormone-free agar medium. The regenerated plants cultivated in the field for about one month accumulated phenylpropanoids such as estragole, anethole, and fenchone in addition to the two monoterpenes described above in radical leaves. Rich accumulations of phenylpropanoids and monoterpenes were observed in the fruits; especially the contents of estragole and anethole were much higher than in radical leaves. PMID- 17268974 TI - Further Sesquiterpene Lactones from Eupatorium altissimum. AB - A reinvestigation of the aerial parts of EUPATORIUM ALTISSIMUM afforded, in addition to several, previously isolated sesquiterpene lactones, five new ones. The structures of these were elucidated by highfield (1)H-NMR spectroscopy. PMID- 17268975 TI - Triterpenoid Saponins from Caltha palustris. AB - Three triterpenoid saponins, hederagenin-3- O-alpha- L-arabinopyranoside, oleanolic acid-3- O-alpha- L-rhamnopyranosyl-(1-->2)-alpha- L-arabinopyranoside and hederagenin-3- O-alpha- L-rhamnopyranosyl-(1-->2)-alpha- L-arabinopyranoside, have been isolated from CALTHA PALUSTRIS (Ranunculaceae). The structures were determined by spectroscopic analysis of the acetates. PMID- 17268976 TI - Further Constituent from the Seeds of Melia azedarach. AB - A new limonoid glycoside has been isolated from the seeds of MELIA AZEDARACH L. and the structure established to be 6,11-diacetoxy-7-oxo-14beta, 15beta epoxymeliacin(1,5-diene-3- O-beta- D-glucopyranoside) by spectral correlations and chemical evidences. PMID- 17268977 TI - 4'-P-Coumaroyl Iridoid Glucosides from Gentiana pedicellata. AB - From flowers and leaves of GENTIANA PEDICELLATA (Gentianaceae), two new iridoids, 4'- P-coumaroyl loganic acid and 4'- P-coumaroyl loganin, have been isolated along with the known iridoid, loganic acid. This is the first report of iridoid glucosides with the 4'-oxygen of the glucose moiety esterified. PMID- 17268978 TI - Amplectol: A Novel Acetylenic Thiophene Derivative from Blumea amplectens var. arenaria. AB - The aerial parts of BLUMEA AMPLECTENS var. ARENARIA afforded taraxasteryl acetate, dihydrosterculic acid, the sesquiterpene ferutinin, and the acetylenic thiophene diol, 3,4-dihydroxy-8-[5'-methylthiophen-2'-yl]-1, 5-octadien-7-yne, named as amplectol. Thestructures were elucidated by spectroscopic methods. A biogenetic pathway for the formation of amplectol in the plant is also suggested. PMID- 17268979 TI - Germacra-1,10Z,4E-dien-12,8alpha-olides from Mikania micrantha. AB - The aerial parts of MIKANIA MICRANTHA from a collection in Paraguay gave, in addition to mikanolide, deoxymikanolide, and miscandenin, five new germacranolides all derived from 14,15-dihydroxygermacra-1(10) E,4 Z-dien 12,8alpha-olide. PMID- 17268980 TI - Two New Anthraquinones from the Seeds of Peganum harmala. AB - Two new anthraquinones have been isolated from the seeds of PEGANUM HARMALA Linn and the structures established as 3,6-dihydroxy-8-methoxy-2-methylanthraquinone (peganone; 1) and 8-hydroxy-7-methoxy-2-methylanthraquinone (peganone; 2) by spectral correlations and chemical evidences. PMID- 17268981 TI - Essential Oil from Origanum dictamnus. AB - The essential oil of ORIGANUM DICTAMNUS L. was obtained by steam distillation with a yield of 0.8% of dry material. The oil was investigated after fractionation on a silica gel column and separation of phenols, by combination of GLC-mass spectrometry. In the analysis, 30 components were found accounting for 98.28% of the oil, the predominating compounds being carvacrol; gamma-terpinene, P-cymene, caryophyllene, borneol, terpin-1-en-4-ol, and carvacrol methyl ether. PMID- 17268982 TI - 2-Amino-5-(N-ethylcarboxamido)-pentanoic Acid from Green Tea Leaves. AB - 2-Amino-5-( N-ethylcarboxamido)-pentanoic acid has been isolated from green tea leaves ( THEA SINESIS). It has been identified from its extensive spectroscopic data. Acid hydrolysis of the compound gave ethylamine and 2-aminoadipic acid. PMID- 17268983 TI - The Essential Oil of Erythroxylum coca. PMID- 17268984 TI - Constituents of essential oils from origanum species growing wild in Turkey. PMID- 17268985 TI - Phytolaccagenic Acid and Phytolaccagenin from Anisomeria coriacea. PMID- 17268986 TI - Indicumenone, A New Bisabolane Ketodiol from Chrysanthemum indicum. PMID- 17268987 TI - Alkaloids of Genista burdurensis. PMID- 17268988 TI - (-)-1-Norvincorine, a New Alkaloid from Vinca minor. PMID- 17268989 TI - Senburiside II, a New Iridoid Glucoside from Swertia japonica. AB - The structure of senbburiside II, a new iridoid glucoside isolated from SWERTIA JAPONICA, was elucidated to be 7-epi-(di- M-hyd-roxybenzoyl)-loganic acid. PMID- 17268990 TI - Eupatoriopicrin 19-O-Linolenoate and Other Constituents from Eupatorium cannabium. AB - The investigation of the roots and aerial parts of EUPATORIUM CANNABIUM afforded, in addition to the sesquiterpene lactones eupatolide, eupatoriopicrin, and eucannabinolide isolated previously, eight further lactones, three of which are new. Furthermore, in addition to known compounds, a new clerodane derivative and two further tremetone derivatives as well as 10-acetoxyneryl acetate were isolated. PMID- 17268991 TI - Cardenolides from Ornithogalum boucheanum. AB - From leaves and bulbs of ORNITHOGALUM BOUCHEANUM (Kunth) Aschers. et Graebn. (Liliaceae), cardenolides were isolated by a combination of column and droplet counter-current chromatography. Their structure elucidation was performed mainly by means of (1)H-NMR, (13)C-NMR, EI-MS, and LD-MS studies as well as by acid and/or enzymatic hydrolysis of the glycosides followed by identification of genins and sugar moieties (TLC, GC). Eight cardenolides were identified as sarmentogenin-3- O-6'-deoxy-beta- D-allosido-beta- D-xylosido-alpha-L-rhamnoside, sarmentogenin-3- O-6'-deoxy-beta- D-allosido-beta- D-xylosido-beta- D-apioside, 15beta, 16alpha-dihydroxyuzarigenin-3- O-beta- D-digitoxosido-beta- D-xylosido alpha- L-rhamnoside, sarmentogenin-3- O-beta- D-digitoxosido-beta- D-xylosido beta- D-apioside, syriogenin-3- O-beta- D-digitoxosido-beta- D-xylosido-alpha- L rhamnoside, sarmentogenin-3- O-alpha- L-rhamnosido-beta- D-apioside, uzarigenin-3 O-beta- D-digitoxosido-beta- D-xylosido-alpha- L-rhamnoside, and digitoxigenin-3 O-6'-deoxy-beta- D-allosido-beta- D-xyloside. This is the first report of the occurrence of 15beta, 16alpha-dihydroxyuzarigenin. The presence of three genins - syriogenin, uzarigenin, and digitoxigenin - in the genus ORNITHOGALUM is described for the first time. For cardenolides, not only the combination of three different monosaccharides in one glycoside is unusual, but, especially, the occurrence of apiose, which was not known for cardiac glycosides until now. PMID- 17268992 TI - HPLC Analysis of the Flavonoid Glycosides from Betulae folium. AB - The main flavonoid glycosides from BETULAE folium are separated with a RP-HPLC method. The mobile phase for the separation of the seven most important compounds (rutin, hyperin, quercetin-3-arabinofuranoside, quercetin-3-arabinopyranoside, quercetin-3-rhamnoside, quercetin-3-glucuronide, and myricetin-3-galactoside) was optimized with the "PRISMA" model, which is a multisolvent optimization system. The isocratic separations were finished within 30 minutes and the peak purity was controlled with diode-array detection. The method can be applied for quantitative determination, as was demonstrated for different samples of B. PENDULA and B. PUBESCENS. PMID- 17268993 TI - Investigation of the Alkaloid Pattern of Datura innoxia Plants by Capillary Gas Liquid-Chromatography-Mass Spectrometry. AB - The alkaloid composition of DATURA INNOXIA plants was analysed by quartz capillary GLC and GLC-MS. Significant differences were found in the alkaloid pattern of the respective plant organs even between different aerial parts. More than 30 alkaloids could be identified. Besides previously known substances, a further 18 tropine ester alkaloids as well as hygrine and tyramine were identified. Seventeen of these alkaloids have not been formerly found in the genus DATURA. Additionally, two hitherto unknown hygrine derivatives, presumably isomeric N-methylpyrrolidinyl-hygrines, were characterized. PMID- 17268994 TI - Chemical ionization mass spectrometry of valepotriates using isobutane as reactant gas. AB - A series of known valepotriates isolated from some VALERIANA species and their transformation products have been studied by CIMS (isobutane). The compounds have been characterized by molecular and protonated molecular ions and some typical fragments. Some information about the location of the acyloxy substituents, especially as regards monoene valepotriates, has been obtained. PMID- 17268995 TI - Effects of Age and Growth Regulators on Growth and Alkaloid Production in Cinchona ledgeriana Leaf-Shoot Organ Cultures. AB - CINCHONA LEDGERIANA Moens et Trimen leaf-shoot organ cultures established and maintained on Murashige and Skoog's medium containing benzyladenine (BA 5 mg/l) were used to study the effects of age and growth regulators on alkaloid production. The total and individual alkaloid content of the leaf-shoot organ cultures increased with age and resembled closely that of the 1-year-old plant which favored quinine production. The 32-week-old tissue cultures contained the same amount of alkaloid as that of the 1-year-old plant (350 mg%). Quinine production was favored by the presence of benzyladenine (5 mg/l), gibberellic acid (5 mg/l) and/or shoots. Quinidine production was high in the presence of indole-3-acetic acid (5 mg/l), the absence of benzyladenine, and/or the presence of roots. High concentrations of abscisic acid and mefluidide inhibited growth and alkaloid production. PMID- 17268996 TI - Chemical and Morphometrical Comparison Between two Peppermint Notomorphs. AB - Flowers and leaves were collected for the comparison of the trichome morphometrical data and the oil chemical data between two peppermint notomorphs ( PALLESCENS and RUBESCENS Camus). The counting of the glandular trichomes was undertaken by means of scanning electron microscope (SEM) and the averages were analyzed for variation (F-ratio). The two plants showed differences in density and number of trichomes, superior values being obtained by the M. RUBESCENS notomorph. The leaves showed a positive correlation between the number of trichomes and the oil yielded. The oil, analyzed using GC-MS coupling, showed high percentages of menthol (53.76) in the leaves and of menthol (36.65), menthone (19.71) and menthofuran (17.70) in the M. RUBESCENS flowers. The M. PALLESCENS notomorph showed high percentages of menthyl acetate (28.86) and moderate percentages of menthol (25.75) in the leaves, while in the flowers menthofuran with 21.10% gave the highest value. PMID- 17268997 TI - Biflavonoids in Hypericum perforatum1; Part 1. Isolation of I3, II8-Biapigenin. AB - From the Soxhlet extract of HYPERICUM PERFORATUM, biflavonoids have been isolated by column chromatography on Sephadex LH 20 and preparative TLC. The structure of the main compound was elucidated by UV-, (1)H- and (13)C-NMR spectroscopy and MS as I3,II8-Biapigenin. PMID- 17268998 TI - Constituents of Evolvolus arbuscula ssp. canus. AB - From the aerial parts of EVOLVOLUS ARBUSCULA ssp. CANUS (Convolvulaceae) the nor sesquiterpenoids, 15-norpanasinsan-5beta-ol-8-one, 15-nor-panasinsan-5,8-dione, and caryophyllenoxide, have been isolated together with some aliphatic compounds and sterols. PMID- 17268999 TI - Glucosides from Abies webbiana. AB - The leaves of A. WEBBIANA yielded methyl betuloside and betuloside. The former has been isolated for the first time from a natural source and the latter is reported from the PINACEAE family for the first time. PMID- 17269000 TI - A new epoxyflavanone from tephrosia hamiltonii1. AB - A phytochemical study of the whole plant of TEPHROSIA HAMILTONII afforded a new flavonoid, characterised as 5, 7-dimethoxy-8-(2, 3-epoxy-3-methylbutyl) flavanone, along with other known compounds. PMID- 17269001 TI - A New Prenylated Flavanone from Erythrina suberosa Roots. AB - The roots of ERYTHRINA SUBEROSA were found to contain a new prenylated flavanone by combined physico-chemical studies. PMID- 17269002 TI - Constituents of the Stems of Arbutus unedo. AB - The dried stems of ARBUTUS UNEDO have been investigated for secondary metabolites. In addition to the previously reported lupeol, ursolic acid, monotropein, unedoside, and stilbericoside, the iridoids geniposide ( 2) and monotropein methyl ester ( 1) have been isolated for the first time from this source. Betulinic acid ( 4) has also been isolated for the first time from this plant. PMID- 17269003 TI - Biotransformations of Quercetin and Apigenin by a Cell Suspension Culture of Cannabis sativa. AB - A cell suspension culture of CANNABIS SATIVA without endogenous flavonoids is able to convert quercetin to quercetin 3- O-glucoside, quercetin 3- O diglucoside, isorhamnetin 3- O-glucoside, and isorhamnetin 3- O-diglucoside. Apigenin is transformed to apigenin 7- O-glucoside and 7- O-glucuronide and to vitexin. PMID- 17269004 TI - Oxygen-Containing Terpene Derivatives from Calendula officinalis. PMID- 17269005 TI - Major Constituents of the Essential Oil of Cleistopholis patens root. PMID- 17269006 TI - Chemical Investigation of Hydrocotyle sibthorpioides. PMID- 17269007 TI - Constituents of the Trunk Resin of Eperua leucantha. PMID- 17269008 TI - Preisocalamenediol, A Constituent of Schinus molle. PMID- 17269009 TI - Volatile Constituents of Ptychopetalum olacoides Root Oil. PMID- 17269010 TI - Isolation of N2-Methyl-1, 2, 3, 4-tetrahydro-beta-carboline from Papaver pavoninum. PMID- 17269011 TI - Antiviral activity of (+)-odorinol1. AB - A phytochemical investigation of AGLAIA ROXBURGHIANA var. Beddomei (Meliaceae) resulted in the isolation of the active principle and its characterisation as (+) odorinol exhibiting strong antiviral activity against Ranikhet disease virus (RVD) in chick embryo. PMID- 17269012 TI - Studies on the Alkaloids of Rhazya stricta. AB - A new strychnos-type alkaloid, bharhingine ( 1), has been isolated from the leaves of RHAZYA STRICTA. Its structure has been assigned on the basis of spectral studies including 2D-NMR measurements. The structure and stereochemistry of another Aspidosperma-type alkaloid, strictanol ( 2) has been investigated by extensive NMR studies including hetero-COSY experiments and NOE difference measurements. Isolation of another strychnos-type alkaloid, vincanicine ( 3), not previously reported from this plant, is also described. PMID- 17269013 TI - Alkaloids of Lycoris guangxiensis1. AB - A new alkaloid, N-allylnorgalanthamine ( 1), was isolated from the bulbs of LYCORIS GUANGXIENSIS Y. Hsu et Q. J. Fan (Amaryllidaceae). Additionally, seven known alkaloids, lycorine, narwedine, galanthamine, lycoramine, crinine, norgalanthamine, and pseudolycorine were also obtained. The structure of 1 was established through the interpretation of spectral data. PMID- 17269014 TI - Further Chromone Alkaloids from Schumanniophyton magnificum. AB - Six further alkaloids have been isolated from the water-soluble fraction of the ethanolic extract of SCHUMANNIOPHYTON MAGNIFICUM Harms. Two of these are the known compounds trigonelline and rohitukine but the other four compounds are novel. Two of these, named schumagnine and N-methylschumagnine, consist of the chromone noreugenin linked to piperidine-related moieties whilst the other two are quaternary amines, the N-methyl analogues of schumanniophytine and isoschumanniophytine. The structures of these compounds have been deduced from their spectral characteristics and by chemical interconversions. PMID- 17269015 TI - Revision of Structures of some Schumanniophyton Alkaloids. AB - The structures of isoschumanniophytine and N-methylschumannificine have been revised on the basis of NOE experiments and their reaction with Gibb's reagent. Revised structures are also proposed for schumannificine, anhydroschumannificine and N-methylanhydroschumannificine. PMID- 17269016 TI - Conversion of artemisinin (qinghaosu) to iso-artemisitene and to 9-epi artemisinin1. AB - The antimalarial agent artemisinin has been converted to two new compounds, ISO artemisitene and 9- EPI-artemisinin. PMID- 17269017 TI - Terpenoids from Elsholtzia Species; II1. Constituents of Essential Oil from a New Chemotype of Elsholtzia cristata. AB - Capillary GC, GC-MS, (1)H-, and (13)C-NMR spectroscopy revealed that the essential oil of ELSHOLTZIA CRISTATA Willd. growing in the Kumaun region contains 88% dehydroelsholtzia ketone along with some minor acylfuran derivatives. This species with respect to its oil composition is unlike that which grows in Japan and Kashmir, and contains elsholtzia ketone as the main constituent. PMID- 17269018 TI - Isolation and 13C-NMR Studies on Three New Furanoditerpenyl Glucosides from Jateorrhiza columba. AB - Three new furanoditerpenyl glucosides, columbinyl glucoside, jateorinyl glucoside, and isojateorinyl glucoside were isolated from JATEORRHIZA COLUMBA roots. Their (13)C-NMR chemical shifts were assigned. PMID- 17269019 TI - Polygoacetophenoside, A New Acetophenone Glucoside from Polygonum multiflorum1. AB - Polygoacetophenoside ( 3), a new acetophenone glucoside, was isolated from POLYGONUM MULTIFLORUM (Polygonaceae), together with quercetin 3- O-galactoside ( 1) and arabinoside ( 2). The structure of the new glucoside was deduced to be 2,3,4,6-tetrahy-droxyacetophenone 3- O-beta- D-glucoside ( 3) by its chemical and spectral data. PMID- 17269020 TI - A New Biflavanone from the Bark of Garcinia kola1. AB - The new I-3', II-3, 3', II-4', I-5, II-5, I-7, II-7-octahydroxy-I-4'-methoxy-I-3, II-8-biflavanone together with known biflavanones GB-1 and GB-2 were isolated from the bark of GARCINIA KOLA. PMID- 17269021 TI - Effect of Sterol Inhibitors on the Incorporation of 14C-Isopentenyl Pyrophosphate into Artemisinin by a Cell-Free System from Artemisia annua Tissue Cultures and Plants. AB - A cell-free system from ARTEMISIA ANNUA L. shoot cultures and plants (shoots and roots) which is capable of incorporating (14)C-isopentenyl pyrophosphate ( (14)C IPP) into artemisinin has been developed. The sterol inhibitors miconazole, AMO 1618, CCC, and MER 29 increased both the incorporation of (14)C-IPP into artemisinin by cell-free extracts and the production of artemisinin in shoot cultures of ARTEMISIA ANNUA. PMID- 17269022 TI - A study on tansy chemotypes. AB - According to Scheu (5), a "pure chemical race" is defined using one oil component, which can be unequivocally considered as the main component. However, another way of defining a chemotype is to observe the whole peak distribution of the chromatogram (6). For example, following crossings between camphor and thujone chemotypes, the thujone types are divided into two different thujone types, thujone A and B (3,4). In this study, 80 per cent of the progeny of the artificial crosses of tansy ( TANACETUM VULGARE L.) appeared to belong to so called "well-defined chemotypes", in which the concentration of the main component varied between 41-99 per cent. The "well-defined chemotypes" were distributed among eight main groups: sabinene, thujone, umbellulone, camphor, bornyl acetate, alpha-pinene, 1,8-cineole, and germacrene-D. The sesquiterpene germacrene-D was identified for the first time in the present study in the essential oil of tansy. Most of these "well-defined chemotypes" were again divided into subgroups A and B. In addition to the "well-defined chemotypes", a number of "mixed chemotypes" were also detected in the crossings. Those chemotypes accounted for 20 per cent of the whole crossing material. PMID- 17269023 TI - A New Alkaloid Ajmalimine from the Roots of Rauwolfia serpentina. AB - A new indole alkaloid ajmalimine has been isolated from the roots of RAUWOLFIA SERPENTINA collected in Thailand. Its structure, 21-(trimethoxybenzoyl)-ajmaline, was established by spectroscopic and chemical means. PMID- 17269024 TI - Indole Alkaloids from Quassia amara. AB - Three beta-carboline alkaloids have been isolated for the first time from the wood of QUASSIA AMARA L. (Simarubaceae) and their structures were determined to be 1-vinyl-4,8-dimethoxy-beta-carboline ( 1), 1-methoxycarbonyl-beta-carboline ( 2), and 3-methylcantin-2,6-dione ( 3) by spectral and chemical means. PMID- 17269025 TI - Occurrence of Psilocybin and Baeocystin in Fruit Bodies of Pluteus salicinus. AB - Using HPLC and TLC, psilocybin and baeocystin but not psilocin were found in extracts of dried fruit bodies of PLUTEUS SALICINUS. Caps contain more psilocybin than stems. The amount of psilocybin varies and was as high as 1.57% in the caps. Urea was also detected. This substance is virtually exclusively localized in the caps. Baeocystin and tryptophan were also found only in the caps. There was a correlation between the content of psilocybin and that of urea. PMID- 17269026 TI - Steroid Alkaloids and Yamogenin from Solanum spirale1. AB - Tomatidenol, 15alpha-hydroxytomatidenol, and yamogenin were isolated from the leaves, and etioline from the roots of SOLANUM SPIRALE. PMID- 17269027 TI - A Further Contribution to the Sesquiterpenoid Constituents of Cymbopogon proximus. AB - Elemol and beta-eudesmol have been isolated from the unsaponifiable fraction of the fatty matter of CYMBOPOGON PROXIMUS. Their structure and configuration were determined by spectroscopic methods. PMID- 17269028 TI - Iridoids in the Flora of Italy; Part 111. Kickxioside, A New Iridoid Glucoside from Kickxia spuria. AB - A new iridoid glucoside, 2, named kickxioside, was isolated from KICKXIA SPURIA. On the basis of spectral data, the structure of antirrhinoside esterified at position 6 by a menthiafolic acid was assigned to 2. The structure was also confirmed by alkaline hydrolysis of 2, which afforded antirrhinoside and menthiafolic acid. PMID- 17269029 TI - New Phthalides from Gentiana pedicellata. AB - Two new phthalides were isolated from the leaves of GENTIANA PEDICELLATA Wall. They were identified as pedicellosine (deglucosylpedicelloside) and 6''- O glucosyl-pedicelloside by their spectral data and chromatographic behaviour. PMID- 17269030 TI - A New Limonoid, Amoorinin, from the Stem Bark of Amoora rohituka. AB - Evidence is presented for the structure of a new limonoid, amoorinin, from the stem bark of AMOORA ROHITUKA on the basis of spectral and chemical evidences. PMID- 17269031 TI - Polysulfanes in the volatile oils of ferula species. AB - A study on the volatile oils of oleogum resin of FERULA SINKIANGENSIS and F. FUKANENSIS by use of GC-MS (CI/EI) showed the presence of twenty-six polysulfanes (disulfanes, trisulfanes, thio-disulfanes, and di-disulfanes). The main component was SEC-butyl- CIS-1-propenyl disulfane in F. SINKIANGENSIS, and SEC-butyl- TRANS 1-propenyl disulfane in F. FUKANENSIS. As minor components, seven new polysulfanes were detected in the oils for the first time. PMID- 17269032 TI - Pinitol from the Leaves of Gliricidia sepium. PMID- 17269033 TI - Loliolide (Calendin) from Calendula officinalis. PMID- 17269034 TI - Isolation of Piceoside from Arctostaphylos uva-ursi. PMID- 17269035 TI - Cryopreservation of plant cell cultures1. AB - The main topics of this brief overview of the cryopreservation of plant cell cultures are (a) the principles behind Cryopreservation procedures as a basis from which the appropriate method for various different cultures can be developed, and (b) the question of how far the characteristics of cell strains are preserved during the freeze-thaw cycle. Of all the species successfully cryopreserved to date, only seven have been investigated with regard to their biochemical capacities. In all these cases the cultures have been shown to retain their growth patterns and biochemical traits. Furthermore, results are available which indicate that this is also valid for long-term storage. Some details are presented on the accumulation of natural products and the biotransformation of cardenolides in frozen-thawed cell cultures. On the other hand, before it is possible to recommend universally applicable cryopreservation protocols, we must better understand the cellular events which determine the freeze-tolerance of plant cell cultures. PMID- 17269036 TI - Nardonoxide, a New Nardosinane-Type Sesquiterpene Ether from Nardostachys chinensis. AB - A new sesquiterpene ether, nardonoxide ( 1), with the nardosinane skeleton, was isolated from the underground parts of NARDOSTACHYS CHINENSIS Batalin (Valerianaceae), growing in the province Sichuan (China). The structure of 1 was elucidated by spectroscopic methods, including 2D-NMR-spectroscopy. PMID- 17269037 TI - New dihydroflavonols from enceliopsis and geraea. AB - Phytochemical analysis of leaves from ENCELIOPSIS NUDICAULIS, E. NUDICAULIS var. CORRUGATA, and GERAEA CANESCENS afforded numerous methylated flavonoids present as resin constituents as well as benzofurans and related compounds extracted from roots. Five new dihydroflavonols present on the leaf surfaces were identified based on their spectral data and on those of the corresponding flavonols obtained by oxidation with NaHSO (3). PMID- 17269038 TI - Two New Saponins from Phytolacca americana. AB - Two new monodesmosidic saponins (Phytolaccosides F and D (2)) have been isolated from the roots of PHYTOLACCA AMERICANA and identified as 3- O-[alpha- L rhamnopyranosyl(1-->2)-beta- D-glucopyranosyl (1-->2)-beta- D xylopyranosyl]phytolaccagenic acid and 3- O-[beta- D-glucopyranosyl(1-->2)-beta- D-xylopyranosyl]phytolaccagenic acid, respectively. PMID- 17269039 TI - New Sesquiterpenes from Ferula jaeschkeana. AB - Phytochemical studies of the FERULA JAESCHKEANA rhizomes resulted in the isolation of two new carotane sesquiterpenes; feruone and the 5alpha-( P hydroxybenzyl)ester of ferutriol. PMID- 17269040 TI - Barbaloin in aloe species. AB - Barbaloin levels in the exudates from the leaves of 68 species of ALOE in the Kew collection have been determined by light absorption at 375 nm following separation by HPLC. The exudates from most species contained between 10-20% although a few concentrations of around 30% were found. The level in the leaf was usually around 1% of thedry weight in plants grown in glasshouses at Kew although some species were found to contain up to 5%. The highest concentrations of barbaloin were found in exudates from young mature leaves just below the apex and the level decreased in older leaves towards the base of the plant. Species in the natural groupings of the genus, Section ANGUIALOE and Group 4, all had appreciable concentrations of barbaloin in the leaf exudates. Species containing barbaloinwere distributed throughout the large heterogeneous Sections EUALOE and PACHYDENDRON with no apparent taxonomic significance. PMID- 17269041 TI - Variation in the Tropane Alkaloid Content of Hyoscyamus muticus Plants and Cell Culture Clones. AB - Systematic studies were carried out on two different strains (Gatersleben and Cairo) of HYOSCYAMUS MUTICUS L. (Solananaceae) in order to analyse the variation in the contents of the two main tropa-alkaloids in individual plants and protoplast-derived cell culture clones. The hyoscyamine content was determined by radioimmunoassay, the scopolamine content by radio- and enzymeimmunoassay and the total tropane alkaloid content by quinuclidinyl benzilate assay. The development stage of the plant is important for alkaloid production. Clear maximal foliar scopolamine and hyoscyamine contents were reached at the onset of flowering and during the full blooming stage, respectively. In the roots the changes in the production of these alkaloids were not considerable. Hyoscyamine is a major alkaloid in the plants as well as in the cell culture clones. In a few exceptions the scopolamine content was greater than that of hyoscyamine, but this phenomenon was not inherited by the cultured clones derived from these plants. High and low tropane alkaloid production was inherited by the selfed F (1), generation plants. Great variability in these alkaloids was observed among individual plants or clones in the same plant or clone population. There was a significant difference between the Cairo strain and the Gatersleben strain as regards their ability to produce tropane alkaloids. Haploid plants of both strains contained more hyoscyamine and scopolamine than the diploid ones. Hyoscyamine and scopolamine were the main alkaloids in the clones and in the plants. Via QNB-assay an interesting clone was found which contains remarkable amounts of unknown tropane group alkaloids. PMID- 17269042 TI - Biotransformation of Tryptamine to Serotonin by Cell Suspension Cultures of Peganum harmala. AB - Cell suspension cultures of P. HARMALA, unable to form serotonin DE-NOVO, hydroxylated fed tryptamine to serotonin independently of the growth cycle up to 20 mg per g dry mass per day. The best biotransformation yield of 80% was obtained with a high cell density (30 g fresh mass/100 ml) and a 5 mM tryptamine concentration in the transformation medium. Under these conditions the cells accumulated serotonin up to 7.5% per unit dry mass, and a maximum yield of 800 mg serotonin/l was achieved. Other indoleethylamines such as alpha-methyltryptamine, N-methyltryptamine, and 6-fluorotryptamine were also transformed to the corresponding 5-hydroxyl compounds, while N,N-dimethyltryptamine, 7 methyltryptamine, tyramine, and phenylethylamine were not hydroxylated. PMID- 17269043 TI - Cryopreservation of Digitalis lanata Shoot Tips. AB - A method for the preservation in liquid nitrogen of shoot tips (meristems) of D. LANATA is described. It includes the following steps: (a) hardening of shoots by cultivation at 4 degrees C for 8 weeks, (b) treatment of the explanted shoot tips with cryoprotectors, e.g., 2 mol DMSO l (-1) for 2 h, (c) either ultrarapid cooling (ca. 4000 K min (-1)) of the shoot tips by submerging in liquid nitrogen or slow cooling (ca. 0.5 K min (-1)) of the shoot tips to -40 degrees C using a suitable freezer, (d) storage of the shoot tips at -196 degrees C in liquid nitrogen, (e) ultrarapid rewarming of the ultrarapidly cooled shoot tips by placing them directly into nutrient medium or rapid rewarming of the ampoules containing the slowly cooled shoot tips with water at 40 degrees C, and (f) recultivation of the shoot tips at the surface of a solidified nutrient medium containing 2.5 micromol BA 1 (-1). About 70% of the shoot tips survived this procedure and about 30% of the shoot tips regenerated shoots. PMID- 17269044 TI - Time-Course Studies in Indole Alkaloid Accumulation and Changes in Tryptophan Decarboxylase and Strictosidine Synthase Activities: A Comparison in Three Strains of Catharanthus roseus Cells. AB - Three different strains of CATHARANTHUS ROSEUS cells were compared during one subculture with regard to tryptophan, tryptamine, ajmalicine, serpentine contents and tryptophane decarboxylase (TDC) (4) and Strictosidine synthase activities. The strains differed greatly in their accumulation of tryptamine and alkaloid. The TDC of all three strains showed the highest activity during the growth phase and declined sharply at the end of this phase. On the contrary, strictosidine synthase activity was the lowest during the growth phase and increased distinctly at the same time when the alkaloids were accumulating. By comparing the three strains with each other, no correlation was observed between the values of enzymatic activities and the contents of accumulated alkaloids. PMID- 17269045 TI - Quinoline Alkaloid Production by Transformed Cultures of Cinchona ledgeriana. AB - A culture of CINCHONA LEDGERIANA, transformed with AGROBACTERLUM TUMEFACIENS A6 capable of growing and producing quinoline alkaloids in medium free of exogenous phytohormones has been obtained. Unlike the untransformed culture of this species, addition of ZR in combination with either IAA or IBA to medium did not affect alkaloid production. Growing the transformed culture in the dark, however, produced a marked enhancement of alkaloid accumulation, up to 50 times that of cultures grown in the light. This dark-dependent accumulation was not confined to any particular time in the growth cycle, although the extent of the stimulatory effect increased the longer cultures were kept in darkness. Blue light was detrimental to alkaloid accumulation but in red or green light the level of accumulation was equivalent to that in the dark. Alternating cultures for several 28-day periods between light and dark conditions resulted in alternate periods of low and higfralkaloid productivity, indicating this was not an adaption effect. These findings correlate to previously reported differences in key enzymes from the biosynthetic pathway. Increasing the phosphate or nitrate concentration above that of Gamborg B5, increasing sucrose above 2% (w/v), replacing sucrose with glucose or adding tryptophan or casamino acids to the medium resuited in lower alkaloid yields by dark-grown cultures of the transformed line. PMID- 17269046 TI - Ajmalicine, Serpentine, and Catharanthine Accumulation in Catharanthus roseus Bioreactor Cultures. AB - A 141, stirred-tank bioreactor was used to investigate the effect of 7% glucose solutions on CATHARANTHUS ROSEUS suspension cultures. Measurement of oxygen uptake rate indicated that alkaloid accumulation occurred primarily during a 20 day transition period between growth-oriented metabolism and maintenance-oriented metabolism. Exposure of the cells to light during this period stimulated catharanthine accumulation and triggered a switch from ajmalicine accumulation to serpentine accumulation. In addition, it suppressed the secretion of both ajmalicine and serpentine; without light nearly 80% of the ajmalicine and serpentine was found in the medium, whereas with light less than 20% was secreted. Alkaloid accumulation was found to be adversely affected by increasing the volume of inoculum culture transferred to a given volume of fresh glucose solution, apparently due to the entry of 2,4-D with the inoculum. PMID- 17269047 TI - The Essential Oil of Perilla ocimoides: A Rich Source of Rosefuran. AB - The essential oil of a strain of PERILLA OCIMOIDES from Bangladesh, cultivated at Lucknow, after GC-MS investigations afforded rosefuran ( 1) as the major constituent (58%) along with 17 others including beta-caryophyllene, perilla ketone ( 2), perillene, alpha-cedrene, germacrene-D, and isobis-abolene. PMID- 17269048 TI - Seasonal Variation of Essential Oil Yield and Composition of Thymus hyemalis. AB - The aerial parts of THYMUS HYEMALIS Lange were collected throughout its complete vegetative cycle (April 1981 to March 1982) from the same locality. The yield and composition of essential oil have been determined in eleven samples with special reference to the content of 1,8-cineole, camphor, thymol, and carvacrol. It was found that the yield and composition of the oil changed from month to month. On the basis of the results obtained, July might be proposed as the most suitable month for harvesting T. HYEMALIS, giving the maximum yield in essential oil, which is especially rich in terpenic hydrocarbons at this time. Maximum levels of 1,8-cineole in August, however, might warrent harvesting during this month as well. PMID- 17269049 TI - The essential oil of olibanum. AB - The essential oil of the oleogum resin "Olibanum" was prepared by direct steam distillation as well as by steam distillation of an N-hexane extract. Physical and chemical constants of the oil were determined. GC-MS was used for the analysis of the oil. Thirty-three components were identified in the steam distilled oil by their Kovats indices on stabilized OV-1 columns and by mass spectral data. The oil contains 62.1% esters, 15.4% alcohols, 9.9% monoterpene hydrocarbons, and 7.1% diterpenes. Certain minor constituents of the steam distilled oil failed to show up in the oil prepared by steam distillation of the N-hexane extract. Both oils exhibit antimicrobial activity, the activity of the steam distilled oil being higher than that of the oil prepared by steam distillation of the N-hexane extract. PMID- 17269050 TI - Radiatoside B and C, Two New Bisiridoid Glucosides from Argylia radiata1. AB - Two new bisiridoid glucosides, radiatoside B and C, together with the known compounds mussaenosidic acid and geniposidic acid, were isolated from the aerial parts of ARGYLIA RADIATA. The structures of the new compounds were established by spectroscopic methods. PMID- 17269051 TI - Elaboration of the ethylidene side chain in the synthesis of indole alkaloids: preparation of (+/-)-deplancheine and its analogues. AB - A new method of elaborating the ethylidene side chain in the synthesis of (+/-) deplancheine ( 1) and its analogues is described. PMID- 17269052 TI - 24zeta-Ethylcholesta-7,22-Dien-3beta-ol: A Possibly Antipyretic Constituent of Artemisia absinthium. PMID- 17269053 TI - Ixerin F from Crepis biennis. PMID- 17269054 TI - Coumarins from the Bark of Amyris lineata. PMID- 17269055 TI - Isorhoifolin, a Flavonoid Glycoside from Periploca nigrescens Leaves. PMID- 17269056 TI - Constituents from Stem Bark of Zanthoxylum pistacifolium. PMID- 17269057 TI - Aurantiamide Acetate in the Stem Bark of Murraya exotica. PMID- 17269058 TI - Chemical Study of Alkaloids from Corydalis bungeana. AB - From the herbs of CORYDALIS BUNGEANA, 16 alkaloids were isolated; 3 of them were identical with acetylcorynoline ( 2), corynoline ( 5), protopine ( 9), which had been obtained before from this plant. A further 11 known alkaloids: dihydrosanguinarine ( 1), acetylisocorynoline ( 3), 11-epicorynoline ( 4), corycavine ( 6), bicuculine ( 7), 12-hydroxycorynoline ( 8), scoulerine ( 12), cheilanthifoline ( 13), yuziphine ( 14), isoboldine ( 15), noryuziphine ( 16) were isolated for the first time from this plant. The tenth, named (+) bungeanine, is a new alkaloid. Its structure has been established to be N-nor 5,14-dehydroacetylcorynoline. The conformation of (+)-bungeanine in solution is also discussed. PMID- 17269059 TI - Composition of the Essential Oil of Ocimum gratissimum Grown in Rwanda1. AB - The essential oil of OCIMUM GRATISSIMUM, growing wild in Rwanda, was investigated by LSC, GLC, and GC-MS. The oil contained 35% thymol and 11% eugenol, which may indicate the occurrence of a new chemotype of the species. A large amount of hydrocarbons (42%) including 18% P-cymene was also found. The oil showed a relatively strong antimicrobial effect. The oil of O. GRATISSIMUM, cultivated in Rwanda from seeds collected in Cameroon, consisted of 47% thymol and only 0.3% eugenol. This sample contained 49% hydrocarbons, including 23% gamma-terpinene. Most of the constituents detected in the oil samples were not previously known to be present in the essential oil of O. GRATISSIMUM. PMID- 17269060 TI - Isolation and Structure of Neriucoumaric and Isoneriucoumaric Acids from the Leaves of Nerium oleander. AB - Two new coumaryloxy triterpenoids, neriucoumaric and isoneriucoumaric acids, have been isolated from fresh, undried and uncrushed leaves of NERIUM OLEANDER and their structures established as 3beta-hydroxy-2alpha-cis- P-coumaryloxy-urs-12-en 28-oic acid and 3beta-hydroxy-2alpha- TRANS- P-coumaryloxy-urs-12-en-28-oic acid respectively, through chemical and spectroscopic methods. PMID- 17269061 TI - New Secoiridoid Glucosides from Ligustrum japonicum. AB - Two new secoiridoid glucosides, oleonuezhenide and isonuezhenide, have been isolated along with known secoiridoid glucosides, from the fruits of LIGUSTRUM JAPONICUM. Their structures have been elucidated on the basis of chemical and spectral data. PMID- 17269062 TI - Flavonol Glycosides from Urtica dioica. AB - Beside sitosterol, sitosterolglucoside, and sopoletine, 7 flavonol glycosides have been isolated for the first time from flowers of URTICA DIOICA (male and female). Their structures were determined by chromatographic and spectroscopic methods (UV, FD-MS, (1)H-NMR, (13)C-NMR). PMID- 17269063 TI - Flavonoid Glycosides from Arnica montana and Arnica chamissonis. AB - Five flavonoid glycosides were identified from flowers of ARNICA MONTANA, four from A. CHAMISSONIS subsp. FOLIOSA var. INCANA. The structures were established on the basis of total acid hydrolysis and spectral data (UV, (1)H-NMR, (13)C-NMR, MS) as hispidulin 7- O-beta-glucoside, isorhamnetin 3- O-beta-glucoside, 3- O beta- D-glucopyranosides of spinacetin, 6-methoxykaempferol and patuletin and querectin 3- O-(6''- O-acetyl)-beta- D-glucopyranoside. The latter compound can serve as distinctive marker between these two ARNICA species. The (1)H-NMR spectra in CD (3)OD are discussed. PMID- 17269064 TI - Catalytic hydrogenation of penstemide: 10-deoxypenstemide, a new valeriana type ester iridoid. AB - Catalytic hydrogenation of the known ester iridoid penstemide over palladium charcoal catalyst provides a new valeriana-type iridoid, identified as 10 deoxypenstemide by spectroscopic methods ( (1)H- and (13)C-NMR). PMID- 17269065 TI - Further Polyenic and Polyynic Carboxamides and Sesamin from Achillea ptarmica. AB - The amides of various polyenic and polyynic carboxylic acids contained in the lipophilic extract from roots, leaves, and flowers of ACHILLEA PTARMICA were separated into several fractions by DCCC. Further separation was possible by subjecting these fractions to HPLC on silica gel (LiChrosorb) and CN-LiChrosorb. With this procedure, sesamin and 15 acid amides of unsaturated carboxylic acids were found. Structure elucidation of the compounds was carried out by means of UV , IR-, (1)H-NMR spectroscopy and MS. PMID- 17269066 TI - Constituents of Andromeda polifolia. AB - A reinvestigation of the aerial parts of ANDROMEDA POLIFOLIA afforded in addition to the known compounds gardenoside ( 1), guaijaverine ( 2) and avicularine ( 3), a new flavonol-dipentoside named polifolioside ( 4). the compounds were isolated employing DCCC and their structures were elucidated by spectroscopic methods. PMID- 17269067 TI - Investigation into the Presence of Pyrrolizidine Alkaloids in Eupatorium cannabinum by Means of Positive and Negative Ion Chemical Ionization GC-MS. AB - It is demonstrated that the combination of positive ion chemical ionization and negative ion chemical ionization GC-MS analyses of herb and root extracts of EUPATORIUM CANNABINUM L. offers a rapid, tentative structure elucidation of pyrrolizidine alkaloids (PAs). Compounds identified in aerial parts of E. CANNAHIMUM in this way are four echinatine isomers, like lycopsamine and intermedine, and a number of their beta-acetyl, beta-angelyl/tiglyl and beta (iso)valeryl esters. PAs without a substituent at C-7 were tentatively identified as supinine and amabiline. In addition to a number of these alkaloids, some beta (iso)butyryl, beta-angelyl/tiglyl, and beta-(iso)valeryl esters of supinine or amabiline were detected in subterranean parts of the plant. PAS with a saturated necine base like the three trachelanthamine isomers and some beta-anglyl/tiglyl esters could be detected in the root material only. A C-9 viridifloryl/trachelanthyl ester of a saturated amino-alcohol like turneforcidine and one of its beta-angelyl/tiglyl esters have also been found. The latter 2 compounds, the beta-(iso)butyryl, the beta-(iso)valeryl, and the beta angelyl/tiglyl esters of supinine or amabiline and the beta-(iso)valeryl ester of an echinatine isomer have not been described in nature before. PMID- 17269068 TI - The Structural Transformation of Gardenoside and Its Related Iridoid Compounds by Acid and beta-Glucosidase. AB - In the course of studies on the metabolism of iridoid compounds, three new compounds derived from 6alpha-hydroxygeniposide and 6beta-hydroxygeniposide, obtained from gardenoside by the hydrochloric acid treatment, were isolated after the hydrolysis with beta-glucosidase. The aglycone of 6beta-hydroxygeniposide was elucidated as 6beta-hydroxygenipin. On the other hand, the aglycones of 6alpha hydroxygeniposide were identified as the mixture of stereoisomers, 6alpha hydroxygenipin and 6alpha-hydroxy-1- EPI-genipin. PMID- 17269069 TI - Uptake of Lupanine by Alkaloid-Storing Epidermal Cells of Lupinus polyphyllus. AB - Epidermis of steins and petioles of LUPINUS POLYPHYLLUS accumulates quinolizidine alkaloids at a concentration of about 30 mM. Since lupanine is synthesized mainly in green mesophyll tissue and not in the epidermis, the alkaloids have to be transported into the epidermal cells. Uptake of [ (3)H]-lupanine into isolated epidermis was 3 to 20 times higher in epidermal cells as compared to the corresponding mesophyll cells. Uptake of lupanine is time dependent and proceeds against a concentration gradient. The uptake depends on temperature and can be characterized by an activation energy of 34 kJ/mol. The process shows multiphasic uptake kinetics and is reduced by SH-group inhibitors (NEM, PHMB) and inhibitors of the energy metabolism (cyanide, antimycine, DNP, CCCP). All these data provide first evidence that simple diffusion cannot be the mechanism for the uptake of lupanine into epidermal cells. The uptake is probably catalyzed by transport proteins. PMID- 17269070 TI - Stimulation of Indole Alkaloid Production in Cell Suspension Cultures of Catharanthus roseus by Abscisic Acid. AB - When added to suspension cultures of CATHARANTHUS ROSEUS, abscisic acid (ABA) stimulated intracellular accumulation of the indole alkaloids catharanthine and ajmalicine in both flask and 30 litre fermenter-scale systems. The response varied, and depended upon the cell line, the concentration and source of the ABA, and the growth phase at which the cells were treated. Precise timing of ABA addition to cells in a 301 fermenter resulted in a catharanthine yield of 85.25 mg/l after 10 days of cultivation. We propose that ABA may be useful for increasing the yield and reducing the production time for commercially useful secondary plant metabolites. PMID- 17269071 TI - Production of Hyoscyamine by 'Hairy Root' Cultures of Datura stramonium. AB - 'Hairy root' cultures of DATURA STRAMONIUM were established following infection of aseptic leaves with AGROBACTERIUM RHIZOGENES. Transformation was confirmed by Southern blotting using [ (32)P]-labelled fragments of the T-DNA as probes. The transformed cultures grew in the absence of added phytohormones and cell mass increased 55-fold during 28 days incubation. Hyoscyamine was a major component of the alkaloid fraction and accounted for at least 0.3% of the dry matter, comparable to pot-grown plants from which the cultures were initiated. Production of hyoscyamine followed growth during the first 15 days of incubation, but continued to increase during the early part of stationary phase. The alkaloid was retained almost entirely in the root tissue. The effects of medium composition and pH on growth and hyoscyamine production are reported. PMID- 17269072 TI - Alkaloid Production in Root and Shoot Cultures of Catharanthus roseus. AB - Root and shoot cultures were induced from seedlings of CATHARANTHUS ROSEUS. Root cultures and cell suspension cultures derived from the root cultures showed similar alkaloid spectra to the roots of intact plants. The alkaloid spectra of shoot cultures and the aerial parts of intact plants were similar to each other but different from those of root and suspension cultures. Illumination affected the alkaloid spectra of shoot cultures. Shoot cultures produced 3',4'anhydrovinblastine, an immediate precursor of vinblastine. PMID- 17269073 TI - Fructan Synthesis in Tissue Cultures of Symphytum officinale; L. Initiation, Differentiation, and Metabolic Activity. AB - Tissue cultures originating from different organs i.e. leaves, leaf-stalks, ovaries, anthers, and roots of SYMPHYTUM OFFICINALE were initiated under various growth conditions and subcultured several times to give the first callus generation. From all these calli, whole plants could be regenerated which again were used for the preparation of tissue cultures resulting in the formation of the second callus generation. The different calli and the regenerated plants were analyzed with respect to the fructan-synthesizing capacity. Only calli derived from the leaves of the original plant synthesized fructan whereas calli derived from ovaries, anthers, and roots, which are known to contain large amounts of fructan, were not capable of synthesizing fructan. The regenerated plants obtained from the first callus generation showed ability for fructan synthesis only if the originating callus synthesized fructan. The calli of the second generation, which were prepared from fructan-containing leaves and roots of regenerated plants, showed the capacity for fructan formation. The calli of the second generation obtained from leaves and roots of regenerated, fructan-free plants were not able to synthesize this specific reserve polysaccharide. From these data it can be concluded that the calli of the first generation prepared from roots, ovaries, and anthers have lost their ability for fructan synthesis. Calli initiated from leaves and leaf-stalks preserved the capacity for fructan formation even after many calli generations and regeneration to entire plants. Different phytohormones used in the tissue cultures had only a slight effect upon the fructan formation. An influence of light on fructan synthesis could not be detected. PMID- 17269074 TI - Accumulation and Biotransformation of Chromenes and Benzofurans in a Cell Suspension Culture of Ageratina adenophora. AB - A cell suspension culture of AGERATINA ADENOPHORA was shown to yield several novel chromene and benzofuran derivatives in minute amounts that were different to the compounds found in seedlings of the same species. The structure elucidation of the new compounds is described. When two of the seedling chromenes (demethoxyencecalin and demethylencecalin) were fed to the cell suspension culture, one biotransformation product each was obtained in high yields (80%) that originated from a hydroxylation at one of the geminal methyl groups of the chromene heterocycle. These products accumulated largely in the growth media even though the presence of cells was necessary for the biotransformations to occur. When the third seedling chromene (encecalin) was fed to the cell auspension culture, no significant biotransformation was noted but several of the benzofurans present as cell culture metabolites showed a significantly increased accumulation in the growth media of the treated cultures. This increased accumulation of benzofurans was found to be inducible also by adding yeast extract to the cell culture. The metabolism of chromenes and bezofurans in the cell suspension culture is discussed. PMID- 17269075 TI - The Acetylenes from Atractylodes macrocephala. AB - The investigation of ATRACTYLODES MACROCEPHALA afforded in addition to known compounds, esters of tetradeca-2,8,10-triene-4,6-diyne-1,12,14-triol. The structures were elucidated by spectroscopic methods and chemical evidence. PMID- 17269076 TI - Volatile Constituents of Montanoa tomentosa and Lippia graveolens. AB - The constituents of the volatile oils of MONTANOA TOMENTOSA and LIPPIA GRAVEOLENS, were investigated using capillary GC/MS. Borneol acetate, beta cubebene, and beta-caryophyllene were found to be the major constituents of the volatile oil of M. TOMENTOSA, while P-cymene, 1,8-cineol, thymol, and carvacrol were the major volatile components of L. GRAVEOLENS. The possible correlation between the high concentration of monoterpenes and the alleged antifertility effect of the title plants is discussed. PMID- 17269077 TI - N-Formylcyclomicrobuxeine - A New Alkaloid from the Leaves of Buxus papillosa. AB - Studies on the alkaloidal constituents of the leaves of BUXUS PAPILLOSA have resulted in the isolation of a new steroidal base, (+)- N-formylcyclomicrobuxeine ( 1). PMID- 17269078 TI - Quaternary Alkaloids of Thalictrum glandulosissimum. PMID- 17269079 TI - Extractives from Ebenaceae: Constituents of the Root and Stem Barks of Diospyros verrucosa. PMID- 17269080 TI - Alkaloids of Genista involucrata and Genista albida. PMID- 17269081 TI - Isolation of Arteannuic Acid from Artemisia annua. PMID- 17269082 TI - Alkaloids of Genista libanotica. PMID- 17269083 TI - Hydroxycinnamylglucoses from Spiraea thunbergii. PMID- 17269084 TI - Chemical Constituents of Centaurea pallescens. PMID- 17269085 TI - Lecithin from Mucuna pruriens. PMID- 17269087 TI - Major Volatile Components of Michelia montana. PMID- 17269086 TI - (+)-Piperitol from Paulownia tomentosa. PMID- 17269088 TI - Flavonoids and Others Constituents from Onopordon macracanthum. PMID- 17269089 TI - Aurantiamide from the Aerial Parts of Scutellaria rivularis. PMID- 17269090 TI - Flavonoids and Coumarins from Achillea schischkinii. PMID- 17269091 TI - Marine Natural Products; VI. A Halogenated Chamigrene Epoxide from the Red Alga Laurencia pinnatifida. PMID- 17269092 TI - Quinolizidine alkaloids: biochemistry, metabolism, and function in plants and cell suspension cultures. AB - Quinolizidine alkaloids constitute about 2% of the alkaloids that are known from plants. In this report, data on chromatography (TLC, cGLC), spectroscopy (MS, NMR), occurrence, biosynthesis (tracer studies, enzymatic experiments), accumulation, transport, degradation, biological activities (pharmacology, chemical ecology), and alkaloid formation in cell cultures are reviewed. PMID- 17269093 TI - Inhibition of mushroom-tyrosinase by aloe extract. AB - Inhibition by ALOE extracts of L-dopa oxidation by mushroom-tyrosinase was examined. 2''- O-Feruloylaloesin and aloesin at concentrations of 0.4 microM showed inhibition of 27 and 30%, respectively. Lineweaver-Burk plots of the concentration of L-dopa in the absence and presence of 2''- O-feruloylaloesin, 0.4 and 0.8 microM, showed that this compound inhibits mushroom-tyrosinase noncompetitively. The K (i) value obtained was 8.5 x 10 (-5) M. 2''- O Feruloylaloesin and aloesin contents were analyzed by a reversed-phase HPLC, and their seasonal variations were observed. PMID- 17269094 TI - Variation of the Amount of Alkaloids in Fruit Bodies of Inocybe aeruginascens. AB - INOCYBE AERUGINASCENS contains psilocybin, baeocystin, and aeruginascin with a still unknown structure in the caps and the stipes. The content of psilocybin and baeocystin has been investigated. The psilocybin and baeocystin content of mushrooms from the same location and with similar mass varied. No correlation has been found between the mass of the mushrooms and the content of psilocybin and baeocystin. There was an extensive correlation between the content of psilocybin and baeocystin. No relation between the location and the content of the indole derivatives seems to exist. PMID- 17269095 TI - A New Isoprenylated Flavone from Brosimopsis oblongifolia. AB - From the roots of BROSIMOPSIS OBLONGIFOLIA a new isoprenylated flavone, named 5' hydroxycudraflavone A ( 1), together with the known cudraflavone A ( 2) and cudraflavone B ( 3) were isolated. Cytotoxic and antimicrobial activity of the compounds were tested. PMID- 17269096 TI - Diterpenoid Alkaloids of Aconitum sungpanase. AB - A new diterpenoid alkaloid, sungpanconitine, was isolated from ACONITUM SUNGPANESE Hand.-Mazz. Its structure was determined on the basis of chemical and spectral evidence. Along with this new compound, four known diterpenoid alkaloids were isolated and identified. PMID- 17269097 TI - Purification of Secologanin from Lonicera tatarica Extracts Using RLCC. AB - Several solvent systems have been studied for the isolation of secologanin from LONICERA TATARICA extracts by means of RLCC. Solvent systems containing ethyl acetate or butanol as water-immiscible components proved to be most suited. PMID- 17269098 TI - The Structures of some Triterpene Saponines from Anagallis arvensis. AB - 5 new triterpene saponines, named anagalloside A, B, C, and desglucoanagalloside A and B, were isolated from the herb of ANAGALLIS ARVENSIS L. (Primulaceae). The structures of the saponines were elucidated by (1)H-, (13)C-NMR spectroscopy, FAB MS, and the methylating and combined methylating-ethylating analysis methods. PMID- 17269099 TI - Gansongon, a New Aristolane Ketone from Nardostachys chinesis Batalin and Structure Revision of an Aristolenol. AB - A new instable aristolane type sesquiterpene ketone, gansongone ( 1), was isolated from the fresh underground parts of NARDOSTACHYS CHINESIS Batalin (Valerianaceae), growing in the province Sichuan (China). The structure of 1 was elucidated by spectroscopic and chemical methods. The structure of the corresponding alcohol 2, which was also found in N. CHINENSIS and formerly regarded as 9-aristolene-1alpha-ol ( 5) has to be revised to l(10)-aristolene 9beta-ol ( 2) from results of 2D-NMR-spectroscopy and oxidation to 1. Besides 1 and 2, the following compounds have been identified in the ethanol extract of the fresh plant material of N. CHINENSIS: nardosinone, nardosinondiol, deoxonarchinol A, beta-sitosterol, oleanolic acid, ethyl beta- D-glucopyranoside. PMID- 17269100 TI - Allicin characterization and its determination by HPLC. AB - Allicin has been synthesized and was purified by liquid chromatography. HPLC chromatograms recorded at different wavelengths reveal pure allicin at similar retention times. The purity of the allicin peak could be confirmed by diode array detection. Pure synthetic allicin has been identified by infrared and mass spectrometry and its spectra were characterized. For the quantitative determination of allicin from different sources, an external standard method has been elaborated. PMID- 17269101 TI - Acridones from Vepris fitoravina and Vepris macrophylla. AB - Four acridones were isolated from the leaves of VEPRIS FITORAVINA and VEPRIS MACROPHYLLA (Rutaceae). Three of these alkaloids were identified as arborinine, evoxanthine, and 1,3-dimethoxy-10-methylacridan-9-one by comparison with authentic samples or by comparison of their properties with published data. The remaining alkaloid was identified on the basis of its spectral data as a new compound, 1-hydroxy-2,3,4-trimethoxyacridan-9-one. PMID- 17269102 TI - Flavonoids from Lycium halimifolium1. AB - Five flavonol glycosides and two genins have been isolated from the leaves of LYCIUM HALIMIFOLIUM Mill. (Solanaceae): quercetin 3- O-rutinoside-7- O-glucoside ( 1), kaempferol3- O-rutinoside-7- O-glucoside( 2), rutin ( 3), nicotiflorin ( 4), isoquercitrin ( 5), quercetin ( 6), and kaempferol ( 7). They were identified on the basis of acid and enzymatic hydrolysis and spectral data. PMID- 17269103 TI - On the Occurrence of Kaempferol-4'-O-beta-D-glucopyranoside in Filipendula ulmaria and Allium cepa. AB - In addition to the main flavonol glycoside spiraeoside in bulbs of ALLIUM CEPA L., kaempferol-4'-glucoside ( 1) has been found in smaller amounts. Traces of other flavonoids could be detected also. PMID- 17269104 TI - Isolation and Insecticidal Activity of (-)-Hardwickiic Acid from Croton aromaticus. PMID- 17269105 TI - Isolation of Epi-Deoxyarteannuin B from Artemisia annua. PMID- 17269106 TI - Further Triterpenes from the Stem Bark of Euphorbia tirucalli. PMID- 17269107 TI - Chondrillasterol from the Tubers of Momordica cochinchinensis. PMID- 17269108 TI - Terpenoids from Salvia potentillifolia. PMID- 17269109 TI - Sitosterol-beta-D-Galactoside from Murraya exotica. PMID- 17269111 TI - Columbianadin: A Novel Coumarin from Heracleum brunonis. PMID- 17269110 TI - Iridoids from gentianaceae plants growing in bulgaria. PMID- 17269112 TI - Essential Oil from Chiliadenus lopadusanus Growing Spontaneously in Lampedusa Island (Italy). PMID- 17269113 TI - An evolutionarily stable strategy model for the evolution of dimorphic development in the butterfly Maculinea rebeli, a social parasite of Myrmica ant colonies. AB - Caterpillars of the butterfly Maculinea rebeli develop as parasites inside ant colonies. In intensively studied French populations, about 25% of caterpillars mature within 1 year (fast-developing larvae [FDL]) and the others after 2 years (slow-developing larvae [SDL]); all available evidence indicates that this ratio is under the control of egg-laying females. We present an analytical model to predict the evolutionarily stable fraction of FDL (pESS). The model accounts for added winter mortality of SDL, general and kin competition among caterpillars, a competitive advantage of SDL over newly entering FDL (priority effect), and the avoidance of renewed infection of ant nests by butterflies in the coming season (segregation). We come to the following conclusions: (1) all factors listed above can promote the evolution of delayed development; (2) kin competition and segregation stabilize pESS near 0.5; and (3) a priority effect is the only mechanism potentially selecting for pESS < 0.5. However, given the empirical data, pESS is predicted to fall closer to 0.5 than to the 0.25 that has been observed. In this particular system, bet hedging cannot explain why more than 50% of larvae postpone growth. Presumably, other fitness benefits for SDL, for example, higher fertility or longevity, also contribute to the evolution of delayed development. The model presented here may be of general applicability for systems where maturing individuals compete in small subgroups. PMID- 17269114 TI - The role of behavioral dynamics in determining the patch distributions of interacting species. AB - The effect of the behavioral dynamics of movement on the population dynamics of interacting species in multipatch systems is studied. The behavioral dynamics of habitat choice used in a range of previous models are reviewed. There is very limited empirical evidence for distinguishing between these different models, but they differ in important ways, and many lack properties that would guarantee stability of an ideal free distribution in a single-species system. The importance of finding out more about movement dynamics in multispecies systems is shown by an analysis of the effect of movement rules on the dynamics of a particular two-species-two-patch model of competition, where the population dynamical equilibrium in the absence of movement is often not a behavioral equilibrium in the presence of adaptive movement. The population dynamics of this system are explored for several different movement rules and different parameter values, producing a variety of outcomes. Other systems of interacting species that may lack a dynamically stable distribution among patches are discussed, and it is argued that such systems are not rare. The sensitivity of community properties to individual movement behavior in this and earlier studies argues that there is a great need for empirical investigation to determine the applicability of different models of the behavioral dynamics of habitat selection. PMID- 17269116 TI - Two-focus fluorescence correlation spectroscopy: a new tool for accurate and absolute diffusion measurements. AB - We present a new method to measure absolute diffusion coefficients at nanomolar concentrations with high precision. Based on a modified fluorescence correlation spectroscopy (FCS)-setup, this method is improved by introducing an external ruler for measuring the diffusion time by generating two laterally shifted and overlapping laser foci at a fixed and known distance. Data fitting is facilitated by a new two-parameter model to describe the molecule detection function (MDF). We present a recorded MDF and show the excellent agreement with the fitting model. We measure the diffusion coefficient of the red fluorescent dye Atto655 under various conditions and compare these values with a value achieved by gradient pulsed field NMR (GPF NMR). From these measurements we conclude, that the new measurement scheme is robust against optical and photophysical artefacts which are inherent to standard FCS. With two-focus-FCS, the diffusion coefficient of 4.26 x 10(-6) cm2s(-1) for Atto655 in water at 25 degrees C compares well with the GPF NMR value of 4.28 x 10(-6) cm2s(-1). PMID- 17269117 TI - Kinetic isotope effects in complex reaction networks: formic acid electro oxidation. AB - The determination of kinetic isotope effects (KIEs) for different reaction pathways and steps in a complex reaction network, where KIEs may affect the overall reaction in various different ways including dominant and minority pathways or the buildup of a reaction-inhibiting adlayer, is demonstrated for formic acid electrooxidation on a Pt film electrode by quantitative electrochemical in situ IR spectroscopic measurements under controlled mass transport conditions. The ability to separate effects resulting from different contributions--which is not possible using purely electrochemical kinetic measurements--allows conclusions on the nature of the rate-limiting steps and their transition state in the individual reaction pathways. The potential independent values of approximately 1.9 for the KIE of formic acid dehydration (CO(ad) formation) in the indirect pathway and approximately 3 for the CO(ad) coverage-normalized KIE of formic acid oxidation to CO2 (direct pathway) indicate that 1) C-H bond breaking is rate-limiting in both reaction steps, 2) the transition states for these reactions are different, and 3) the configurations of the transition states involve rather strong bonds to the transferred D/H species, either in the initial or in the final state, for the direct pathway and--even more pronounced--for formic acid dehydration (CO(ad) formation). PMID- 17269118 TI - Alternating spin chains: controlled assembly from bimetallic building blocks and QMC simulation of spin correlation. AB - By using the compartmental dinucleating pyrazolate ligand HL, dinickel(II) complexes [LNi2(micro-N3)(acetone)2]X2 (1: X = CIO4; 2: X = BPh4) and tetranickel(II) complex [{LNi2(micro-N3)(MeOH)2](CI04)4 (3) have been prepared and structurally characterized. Complexes 1 and 2 differ in the torsion along the bridging micro-1,3-azide moiety, while the azido ligands in 3 adopt an unusual micro-1,1,3 bridging mode to connect the two subunits. All three complexes show overall antiferromagnetic coupling and an S = 0 ground state, but the torsion along the azide moiety is a determining factor for the coupling strength. Compounds 1 and 2 serve as preorganized building blocks for the controlled synthesis of alternating 1D polymeric structures 4-6 by replacement of their labile acetone ligands by additional azido ligands. Due to the modular synthetic approach, 4-6 can be described as Heisenberg antiferromagnetic systems with inherent bond alternation (HABA), whereby the organic ligand framework ensures that the individual nickel/azido chains are well isolated in the crystal lattice. Like their precursors, 4-6 are mainly distinguished by torsion along the micro 1,3-azido bridges, both within and between the bimetallic constituents. Magnetic measurements confirm an overall 5 = 0 ground state for 4-6, and coupling parameters have been deduced from quantum Monte Carlo simulations. The two J values for the alternating 1D chains can be clearly assigned on the basis of the magnetostructural correlations established for the bimetallic building blocks. The alternation ratio gamma = J2J1(-1) places the three new systems in the HABA regime for a singlet-dimer ground state. PMID- 17269119 TI - Development of parallel density functional program using distributed matrix to calculate all-electron canonical wavefunction of large molecules. AB - We developed a new parallel density-functional canonical molecular-orbital program for large molecules based on the resolution of the identity method. In this study, all huge matrices were decomposed and saved to the distributed local memory. The routines of the analytical molecular integrals and numerical integrals of the exchange-correlation terms were parallelized using the single program multiple data method. A conventional linear algebra matrix library, ScaLAPACK, was used for matrix operations, such as diagonalization, multiplication, and inversion. Anderson's mixing method was adopted to accelerate the self-consistent field (SCF) convergence. Using this program, we calculated the canonical wavefunctions of a 306-residue protein, insulin hexamer (26,790 orbitals), and a 133-residue protein, interleukin (11,909 orbitals) by the direct SCF method. In regard to insulin hexamer, the total parallelization efficiency of the first SCF iteration was estimated to be 82% using 64 Itanium 2 processors connected at 3.2 GB/s (SGI Altix3700), and the calculation successfully converged at the 17-th SCF iteration. By adopting the update method, the computational time of the first and the final SCF loops was 229 min and 156 min, respectively. The whole computational time including the calculation before the SCF loop was 2 days and 17 h. This study put the calculations of the canonical wavefunction of 30,000 orbitals to practical use. PMID- 17269120 TI - Computation of large systems with an economic basis set: structures and reactivity indices of nucleic acid base pairs from density functional theory. AB - We show here that an economic basis set can describe nucleic acid base pairs involving the hydrogen bond interactions in density functional calculations. The economic basis set in which the polarization function is added only to oxygen and nitrogen atoms of strong electronegativity can predict reliable geometric structures and dipole moment of nucleic acid base pairs, comparable to those obtained from the basis set of 6-31G* in B3LYP calculations. Combining single point calculations with the standard basis set on the geometric structures optimized by the economic basis set, the present approach has predicted accurate natural bond orbital charge, binding energy, electronegativity, hardness, softness, and electrophilicity index. The principle for basis selection presented in this study can be regarded as a general guideline in the computation of large biological systems with considerably high accuracy and low computational expense. PMID- 17269121 TI - Kinetic mechanism of the hydrogen abstraction reactions of the chlorine atoms with CH3CF2Cl and CH3CFCl2: a dual level direct dynamics study. AB - The mechanisms of the reactions: CH(3)CFCl(2) + Cl (R1) and CH(3)CF(2)Cl + Cl (R2) are studied over a wide temperature range (200-3000 K) using the dual-level direct dynamics method. The minimum energy path calculation is carried out at the MP2/6-311G(d,p) and B3LYP/6-311G(d,p) levels, and energetic information is further refined by the G3(MP2) theory. The H-abstraction from the out-of-plane for (R1) is the major reaction channel, while the in-plane H-abstraction is the predominant route of (R2). The canonical variational transition-state theory (CVT) with the small-curvature tunneling (SCT) correction method is used to calculate the rate constants. Using group-balanced isodesmic reactions and hydrogenation reactions as working chemical reactions, the standard enthalpies of formation for CH(3)CFCl(2), CH(3)CF(2)Cl, CH(2)CFCl(2), and CH(2)CF(2)Cl are evaluated at the CCSD(T)/6-311 + G(3df,2p)//MP2/6-311G(d,p) level of theory. The results indicate that the substitution of fluorine atom for the chlorine atom leads to a decrease in the C-H bond reactivity with a small increase in reaction enthalpies. Also, for all reaction pathways the variational effect is small and the SCT effect is only important in the lower temperature range on the rate constants. PMID- 17269122 TI - Tl(I)-the strongest structure-breaking metal ion in water? A quantum mechanical/molecular mechanical simulation study. AB - Structural and dynamical properties of the Tl(I) ion in dilute aqueous solution have been investigated by ab initio quantum mechanics in combination with molecular mechanics. The first shell plus a part of the second shell were treated by quantum mechanics at Hartree-Fock level, the rest of the system was described by an ab initio constructed potential. The radial distribution functions indicate two different bond lengths (2.79 and 3.16 A) in the first hydration shell, in good agreement with large-angle X-ray scattering and extended X-ray absorption fine structure spectroscopy results. The average first shell coordination number was found as 5.9, and several other structural parameters such as coordination number distributions, angular distribution functions, and tilt- and theta-angle distributions were evaluated. The ion-ligand vibration spectrum and reorientational times were obtained via velocity auto correlation functions. The Tl-O stretching force constant is very weak with 5.0 N m(-1). During the simulation, numerous water exchange processes took place between first and second hydration shell and between second shell and bulk. The mean ligand residence times for the first and second shell were determined as 1.3 and 1.5 ps, respectively, indicating Tl(I) to be a typical "structure-breaker". The calculated hydration energy of -84 +/- 16 kcal mol(-1) agrees well with the experimental value of -81 kcal mol(-1). All data obtained for structure and dynamics of hydrated Tl(I) characterize this ion as a very special case among all monovalent metal ions, being the most potent "structure-breaker", but at the same time forming a distinct second hydration shell and thus having a far-reaching influence on the solvent structure. PMID- 17269123 TI - Effect of different treatments of long-range interactions and sampling conditions in molecular dynamic simulations of rhodopsin embedded in a dipalmitoyl phosphatidylcholine bilayer. AB - The present study analyzes the effect of the simulation conditions on the results of molecular dynamics simulations of G-protein coupled receptors (GPCRs) performed with an explicit lipid bilayer. Accordingly, the present work reports the analysis of different simulations of bovine rhodopsin embedded in a dipalmitoyl phosphatidylcholine (DPPC) lipid bilayer using two different sampling conditions and two different approaches for the treatment of long-range electrostatic interactions. Specifically, sampling was carried out either by using the statistical ensembles NVT or NPT (constant number of atoms, a pressure of 1 atm in all directions and fixed temperature), and the electrostatic interactions were treated either by using a twin-cutoff, or the particle mesh Ewald summation method (PME). The results of the present study suggest that the use of the NPT ensemble in combination with the PME method provide more realistic simulations. The use of NPT during the equilibration avoids the need of an a priori estimation of the box dimensions, giving the correct area per lipid. However, once the system is equilibrated, the simulations are irrespective of the sampling conditions used. The use of an electrostatic cutoff induces artifacts on both lipid thickness and the ion distribution, but has no direct effect on the protein and water molecules. PMID- 17269124 TI - New computational strategy to analyze the interactions of ERalpha and ERbeta with different ERE sequences. AB - The importance of computational methods for the simulation and analysis of biological systems has increased during the last years. In particular, methods to predict binding energies are developing not only with the aim of ranking the affinities between two or more complexes, but also to quantify the contribution of different types of interaction. In this work, we present the application of HINT, a non Newtonian force field, to rank the affinities of complexes formed by estrogen receptors (ER) alpha and beta and different estrogen responsive elements (ERE) near the estrogen-regulated genes. We used the crystallographic coordinates of the DNA binding domain of ERalpha complexed to a consensus ERE as a starting point to simulate several complexes in which some nucleotides in the ERE sequence were mutated. Moreover, we used homology modeling methods to create the structure of the complexes between the DNA binding domain of ERbeta (for which no experimental structures are currently available) and the same ERE sequences. Our results show that HINT is able to rank the affinities of ERalpha and ERbeta for different ERE sequences, and to correctly identify the positions on the DNA sequence that are most important for binding affinity. Moreover, the HINT output gives us the opportunity to identify and quantify the role played by each single atom of amino acids and nucleotides in the binding event, as well as to predict the effect on the binding affinity for other nucleotide mutations. PMID- 17269125 TI - Computational chemistry approach to protein kinase recognition using 3D stochastic van der Waals spectral moments. AB - Three-dimensional (3D) protein structures now frequently lack functional annotations because of the increase in the rate at which chemical structures are solved with respect to experimental knowledge of biological activity. As a result, predicting structure-function relationships for proteins is an active research field in computational chemistry and has implications in medicinal chemistry, biochemistry and proteomics. In previous studies stochastic spectral moments were used to predict protein stability or function (Gonzalez-Diaz, H. et al. Bioorg Med Chem 2005, 13, 323; Biopolymers 2005, 77, 296). Nevertheless, these moments take into consideration only electrostatic interactions and ignore other important factors such as van der Waals interactions. The present study introduces a new class of 3D structure molecular descriptors for folded proteins named the stochastic van der Waals spectral moments ((o)beta(k)). Among many possible applications, recognition of kinases was selected due to the fact that previous computational chemistry studies in this area have not been reported, despite the widespread distribution of kinases. The best linear model found was Kact = -9.44 degrees beta(0)(c) +10.94 degrees beta(5)(c) -2.40 degrees beta(0)(i) + 2.45 degrees beta(5)(m) + 0.73, where core (c), inner (i) and middle (m) refer to specific spatial protein regions. The model with a high Matthew's regression coefficient (0.79) correctly classified 206 out of 230 proteins (89.6%) including both training and predicting series. An area under the ROC curve of 0.94 differentiates our model from a random classifier. A subsequent principal components analysis of 152 heterogeneous proteins demonstrated that beta(k) codifies information different to other descriptors used in protein computational chemistry studies. Finally, the model recognizes 110 out of 125 kinases (88.0%) in a virtual screening experiment and this can be considered as an additional validation study (these proteins were not used in training or predicting series). PMID- 17269126 TI - Electron correlation: the many-body problem at the heart of chemistry. AB - The physical interactions among electrons and nuclei, responsible for the chemistry of atoms and molecules, is well described by quantum mechanics and chemistry is therefore fully described by the solutions of the Schrodinger equation. In all but the simplest systems we must be content with approximate solutions, the principal difficulty being the treatment of the correlation between the motions of the many electrons, arising from their mutual repulsion. This article aims to provide a clear understanding of the physical concept of electron correlation and the modern methods used for its approximation. Using helium as a simple case study and beginning with an uncorrelated orbital picture of electronic motion, we first introduce Fermi correlation, arising from the symmetry requirements of the exact wave function, and then consider the Coulomb correlation arising from the mutual Coulomb repulsion between the electrons. Finally, we briefly discuss the general treatment of electron correlation in modern electronic-structure theory, focussing on the Hartree-Fock and coupled cluster methods and addressing static and dynamical Coulomb correlation. PMID- 17269127 TI - Semilobar holoprosencephaly prenatal diagnosis: an unexpected complex rearrangement in a de novo apparently balanced reciprocal translocation on karyotype. AB - We report a semilobar holoprosencephaly (HPE) in a post-intracytoplasmic-sperm injection pregnancy. It was suggested by ultrasonography (US), documented on karyotype, identified with magnetic resonance imaging (MRI), established after birth and confirmed on post-mortem autopsy. An amniocentesis revealed a de novo apparently balanced reciprocal translocation 46,XY, t(7;8) (q31.3;q12). Fluorescence in situ hybridization (FISH) identified a deletion in the region of the Sonic Hedgehog gene (SHH) on der(8); nevertheless, the subtelomeric regions for chromosomes 7 and 8 were present. The parents decided to continue the pregnancy; a boy was born and survived for 3 days. The brain autopsy confirmed the semilobar HPE previously noted on US and MRI. Further, band-specific FISH revealed, in addition to SHH deletion, the presence of an inversion in the 7q translocated material on der(8). The parents' karyotypes were normal. An unexpected complex rearrangement was present in a de novo apparently balanced reciprocal translocation in a semilobar HPE. PMID- 17269128 TI - Maternal serum free-beta-chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10-13(+6) weeks in relation to co-variables in pregnant Saudi women. AB - OBJECTIVE: To establish normative values and distribution parameters of first trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. METHODS: A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. RESULTS: All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free beta-hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). CONCLUSIONS: The normative values and distribution parameters for fetal NT, maternal serum free beta-hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined. PMID- 17269129 TI - Ubiquitous and uniform in vivo fluorescence in ROSA26-EGFP BAC transgenic mice. AB - Transplantation studies and cell lineage analyses require the ability to explicitly distinguish morphologically identical cells that have an identifiable marker indicating their origin in vivo. Several reporter mouse strains have been generated for such studies, but pancellular detection of the marker in all tissues has not been achieved. In this report, we describe the generation of transgenic mice that express enhanced green fluorescent protein (EGFP) under control of a 187 kb bacterial artificial chromosome (BAC) containing the murine ROSA26 locus, and show several advantages over existing EGFP reporter lines. It is demonstrated that EGFP is ubiquitously and reproducibly expressed from the murine BAC transgene in all organs and tissues analyzed, including the hematolymphoid compartment. Using this new reporter strain in hematopoietic cell transplantation studies, it is demonstrated that leukocytes in recipients maintain uniform transgene expression and are easily distinguished by flow cytometric analysis of live cells. The results suggest that the ROSA26 BAC is an efficient strategy for expressing complex transgene cassettes in vivo. PMID- 17269130 TI - Complex genomic rearrangement in CCS-LacZ transgenic mice. AB - The cardiac conduction system (CCS)-lacZ insertional mouse mutant strain genetically labels the developing and mature CCS. This pattern of expression is presumed to reflect the site of transgene integration rather than regulatory elements within the transgene proper. We sought to characterize the genomic structure of the integration locus and identify nearby gene(s) that might potentially confer the observed CCS-specific transcription. We found rearrangement of chromosome 7 between regions D1 and E1 with altered transcription of multiple genes in the D1 region. Several lines of evidence suggested that regulatory elements from at least one gene, Slco3A1, influenced CCS-restricted reporter gene expression. In embryonic hearts, Slco3A1 was expressed in a spatial pattern similar to the CCS-lacZ transgene and was similarly neuregulin-responsive. At later stages, however, expression patterns of the transgene and Slco3A1 diverged, suggesting that the Slco3A1 locus may be necessary, but not sufficient to confer CCS-specific transgene expression in the CCS-lacZ line. PMID- 17269132 TI - Recombinant preparation and characterization of interactions for a calmodulin binding chromogranin A peptide and calmodulin. AB - Chromogranin-derived peptides have important and varied biological activities. They affect a wide spectrum of targets such as fungal membranes, blood vessels, myocardial cells, and pancreatic cells. Despite the biological significance and the diverse activities, the molecular mechanisms of the interactions between the peptides and the target proteins have not been well understood. Here, we studied the interaction between a chromogranin A-derived peptide (CGA40-65) and its target protein, calmodulin, with NMR spectroscopy. Calmodulin was easily prepared with standard recombinant technology, but CGA40-65 posed challenges requiring multistep procedures. The recombinantly produced peptide retained the calmodulin binding property of the full-length CGA, as shown by the HSQC binding experiment. By applying resonance assignments, we identified the residues in calmodulin involved in the CGA40-65 binding. We also found that the peak changes are close to those exhibited by the peptides having the wrap-around binding mechanism. Further analysis revealed that the CGA40-65-induced changes are more similar to those by CaMKIp peptide than those by smMLCKp peptide among the wrap-around binding peptides, suggesting that CGA40-65 can be categorized as a CaMKIp-like peptide. Our report is the first residue-resolution mechanistic study involving chromogranin peptides and their target proteins. Our approaches should be applicable to interaction studies involving other chromogranin-derived peptides and their cellular target proteins. PMID- 17269131 TI - Severe hypokinesis caused by paraneoplastic anti-Ma2 encephalitis associated with bilateral intratubular germ-cell neoplasm of the testes. AB - We report a 40-year-old man with severe hypokinesis as paraneoplastic manifestation of a microscopic "carcinoma in situ" of the testis. The young age of the patient, along with progressive neurologic deterioration, detection of anti-Ma2 antibodies, and ultrasound findings of bilateral microcalcifications, led to bilateral orchiectomy, revealing the tumor in both testes. After orchiectomy, neurological symptoms stabilized, but the patient eventually died of systemic complications caused by his severe neurological deficits. Anti-Ma2 paraneoplastic encephalitis should be considered in patients with severe hypokinesis, and intensive investigation and aggressive approach to treatment is encouraged to prevent progression of the neurological deficits. PMID- 17269133 TI - The [Tc(N)(PNP)]2+ metal fragment labeled cholecystokinin-8 (CCK8) peptide for CCK-2 receptors imaging: in vitro and in vivo studies. AB - The radiolabeling of the natural octapeptide CCK8, derivatized with a cysteine residue (Cys-Gly-CCK8), by using the metal fragment [99mTc(N)(PNP3)]2+ (PNP3 = N,N-bis(dimethoxypropylphosphinoethyl)methoxyethylamine) is reported. The [99mTc(N)(NS-Cys-Gly-CCK8)(PNP3)]+ complex was obtained according to two methods (one-step or two-step procedure) that gave the desired compound in high yield. The complex is stable in aqueous solution and in phosphate buffer. In vitro challenge experiments with an excess of cysteine and glutathione indicate that no transchelation reactions occur, confirming the high thermodynamic stability and kinetic inertness of this compound. Stability studies carried out in human and mouse serum, as well as in mouse liver homogenates, show that the radiolabeled compound remains intact for prolonged incubation at 37 degrees C. Binding properties give Kd (19.0 +/- 4.6 nmol/l) and Bmax (approximately 10(6) sites/cell) values in A431 cells overexpressing the CCK2-R. In vivo evaluation of the compound shows rapid and specific targeting to CCK2-R, a fourfold higher accumulation compared to nonreceptor expressing tumors. PMID- 17269134 TI - Biaxial mechanical evaluation of cholecyst-derived extracellular matrix: a weakly anisotropic potential tissue engineered biomaterial. AB - A new acellular, natural, biodegradable matrix has been discovered in the cholecyst-derived extracellular matrix (CEM). This matrix is rich in collagen and contains several other macromolecules useful in tissue remodeling. In this study, the principal material axes, collagen fiber orientations, and biaxial mechanical properties in a physiological loading regime were characterized. Fiber direction was determined by polarized light microscopy, and the principal axes and degree of anisotropy were determined mechanically. Macroscopic equibiaxial strain tests were then conducted on preconditioned specimens. While 13% of the area of CEM contains collagen fibers oriented between 50 degrees and 60 degrees from the neck fundus axis, the principal material axis was oriented 63 degrees +/- 13.7 degrees , with an aspect ratio of 0.11 +/- 0.06, indicating a weak anisotropy in that direction. Under biaxial loading, CEM exhibited a large toe region followed by an exponential rise in stress in both principal and perpendicular axis directions, similar to other materials currently under research. There was no significant difference between the biaxial stress-strain profile and the burst stress-strain profile. The results demonstrate that CEM is weakly anisotropic and it has the ability to support large strains across a physiological loading regime. PMID- 17269135 TI - Structure and strength at the bonding interface of a titanium-segmented polyurethane composite through 3-(trimethoxysilyl) propyl methacrylate for artificial organs. AB - The objective of this study was to investigate the structure and strength at the bonding interface of a titanium (Ti)-segmented polyurethane (SPU) composite through (3-trimethoxysilyl) propyl methacrylate (gamma-MPS) for artificial organs. The effects of the thickness of the gamma-MPS layer on the shear bonding strength between Ti and SPU were investigated. Ti disks were immersed in various concentrations of gamma-MPS solutions for several immersion times. The depth profiles of elements and the thickness of the gamma-MPS layer were determined by glow discharge optical emission spectroscopy and ellipsometry, respectively. The bonding stress at the Ti/gamma-MPS/SPU interface was evaluated with a shear bonding test. Furthermore, the fractured surface of a Ti-SPU composite was observed by optical microscopy and characterized using X-ray photoelectron spectroscopy. Consequently, the thickness of the gamma-MPS layer was controlled by the concentration of the gamma-MPS solution and immersion time. The shear bonding stress at the interface increased with the increase of the thickness of the gamma-MPS layer. Therefore, the control of the thickness of the gamma-MPS layer is significant to increase the shear bonding stress at the Ti/gamma-MPS/SPU interface. These results are significant to create composites for artificial organs consisting of other metals and polymers. PMID- 17269136 TI - Effects of oncostatin M on secretion of vascular endothelial growth factor and reconstruction of liver-like structure by fetal liver cells in monolayer and three-dimensional cultures. AB - Vascular endothelial growth factor (VEGF) is crucial for the development and regeneration of the liver. However, there have been no reports about VEGF secretion by cultured fetal liver cells (FLCs). In the present study, the effects of oncostatin M (OSM), which strongly stimulates the growth and albumin secretion of FLCs, on VEGF secretion and morphological changes of long-term cultured FLCs were investigated under three-dimensional (3-D) and monolayer conditions. The cultured FLCs proliferated well and showed stable secretion of VEGF for up to 1 month under both monolayer and 3-D culture conditions. The addition of OSM to cultured cells strongly enhanced VEGF secretion. Compared with 3-D cultures, VEGF secretion per cell was higher in monolayer cultures. After 1 month in culture, the FLCs in 3-D cultures formed large aggregates like liver tissue, and FLCs also formed colonies and duct-like structures after several months of culture even under monolayer conditions. In conclusion, OSM stimulated the secretion of VEGF by cultured FLCs, which seemed to contribute to the development of a liver-like structure. PMID- 17269137 TI - In vivo experiments with tracheostoma tissue connector prototypes. AB - In cancer patients who have undergone total surgical removal of the larynx, ideally voice rehabilitation should be performed using a shunt valve (placed in a fistula of the tracheo-esophageal wall) and a tracheostoma valve (TSV) to enable hands-free tracheo-esophageal speech. A tracheostoma is created by suturing the trachea into the lower anterior part of the neck, and a TSV is a device that can be placed at the stoma. Unfortunately, many patients are unable to use a TSV, mainly due to fixation difficulties. To improve the fixation of the TSV, tracheostoma tissue connector (TS-TC) prototypes have been designed. Prototype 1 consisted of a titanium ring, inner diameter 30 mm, with a circular polypropylene mesh glued to it with silicone adhesive. Four holes had been drilled into the ring for the insertion of sub- and percutaneous screws. Prototype 2 consisted of a silicone rubber ring, inner diameter 30 mm, combined with polypropylene mesh and four titanium inserts that functioned as a base plate for the insertion of sub- and percutaneous screws. In adult female goats a tracheostoma was created and the prototypes were implanted. After 6 weeks of subcutaneous implantation, percutaneous screws were inserted. After twelve weeks, the experiment was terminated and the implants with the surrounding tissues were processed and examined histologically. The clinical appearance during weeks 7-12 varied from very poor to relatively good. Histologically, the implants showed a uniform inflammatory response. We found that all the tissue surrounding the screws showed signs of epithelial down growth. It was concluded that the two-stage implantation procedure of our prototype TS-TCs in this animal model was unsuccessful. Additional research efforts are necessary to improve tissue immobilization and to devise reliable fixation systems for TSVs. PMID- 17269138 TI - Submicron poly(L-lactic acid) pillars affect fibroblast adhesion and proliferation. AB - Controlling cell adhesion and proliferation on synthetic polymers is key to tissue engineering scaffold development. It is accepted that surface topography influences cell response but the mechanisms behind this remain unclear. In this work, cell response is assessed to topographies larger than focal complexes (FXs) but smaller than focal adhesions (FAs). Poly(L-lactic acid) was patterned with 400- and 700-nm pillars via replication molding. Human fibroblast adhesion and proliferation were assessed. The development of focal contacts and actin microfilaments were evaluated via immunofluorescence. Cell interactions with surface topography were observed via scanning electron microscopy. Initial fibroblast adhesion (<1 day) increased with texture as 400 nm > 700 nm > smooth, but proliferation (>1 day) decreased with texture. Increased FX formation was observed on textured surfaces. However, FAs were narrower on textured surfaces compared with smooth materials and confined to interpillar regions. SEM showed that fibroblasts deformed the 400-nm pillars. It is hypothesized that surface texture mediated FX formation and increased cell adhesion, possibly via increased material surface area. Texture geometry limited maturation of FXs to FAs, decreasing proliferation. We conclude that surface texture can alter cell adhesion and proliferation and propose geometric constraint as a mechanism for this process. PMID- 17269139 TI - Discrete crosslinked fibrin microthread scaffolds for tissue regeneration. AB - In this study, we report on the development of discrete fibrin microthreads as well as novel scaffolds composed of arrays of fibrin threads. These scaffolds exhibit mechanical properties that are significantly greater than fibrin gels and cellular responses suggesting that the materials are conducive to the development of organized, aligned tissues. Fibrin microthreads were produced by coextruding solutions of 70 mg/mL fibrinogen and 6 U/mL thrombin through small diameter polyethylene tubing. Uncrosslinked fibrin microthreads averaged 55-65 microm in hydrated diameter and achieved ultimate tensile strengths approaching 4.5 MPa. The strengths and stiffnesses of the microthreads were approximately twofold greater when the materials were treated with exposure to ultraviolet (UV) light. Although UV crosslinking attenuated fibroblast proliferation, uncrosslinked fibrin microthreads supported fibroblast attachment, proliferation, and alignment, suggesting that they represent a viable biomaterial for the aligned regeneration of tissues. Because of the physiologic roles of fibrin matrices in the early phase of wound healing, we anticipate that these fibrin-based microthreads will direct the spatially and temporally complex processes of cell mediated tissue ingrowth and regeneration. PMID- 17269140 TI - Alginate/polyethylene glycol blend fibers and their properties for drug controlled release. AB - Fibers of alginate and polyethylene glycol (PEG), with salicylic acid (SA) as model drug incorporated in different concentrations, were obtained by spinning their solution through a viscose-type spinneret into a coagulating bath containing aqueous CaCl(2) and ethanol. Chemical, morphological, and mechanical properties characterization were carried out, as well as the studies of the factors that influence the drug releasing from alginate/PEG fibers. These factors included the component ratio of alginate and PEG, the loaded amount of SA, the pH, and the ionic strength of the release solution and others. The best values of the tensile strength at 13.41 cN/tex and breaking elongation at 23.13% of blend fibers were obtained when the PEG content was 5 wt %; the water swelling ratio (WSR) of blend fibers increased as the composition of PEG was raised. The results of controlled release tests showed that the amount of SA released increased with an increase in the proportion of PEG present in the fiber. Moreover, the release rate of drug decreased as the amount of drug loaded in the fiber increased, but the cumulative release amount is increasing. The alginate/PEG fibers were also sensitive to pH and ionic strength. For pH 7.4 the drug release was faster compared to pH 1.0, being simultaneously accelerated by a higher ionic strength. All the results indicated that the alginate/PEG fiber was potentially useful in drug delivery systems. PMID- 17269141 TI - Development of a local vasodilator delivery system using fibrin glue to prevent arterial graft from spasm. AB - The clinical benefits of coronary artery bypass graft operations can be compromised by postoperative vasospasm. Traditionally, local papaverine (PPV) has been employed during the procedure to prevent and counteract vasospasm. But the relatively short action period limited its application. Fibrin glue (FG) might be a potential carrier of PPV for counteracting vasospasm in a longer action period than PPV solution. After FG incorporated with PPV (PPV-FG) was locally administrated in axillary and femoral arteries of dogs, PPV concentrations in artery vessels surrounding the administration sites were compared with the concentrations at the same sites in dogs given PPV solution. The properties of PPV's release in vitro and maintenance in vessel as well as the influence on the mean peripheral blood pressure and drug concentration in peripheral vein after the introduction PPV-FG on the surface of artery in dogs were evaluated. FG was considered to provide a sustained release of PPV and could maintain a high PPV concentration in artery vessel around the administration site. The results suggested that FG was an effective substrate for reserving PPV in the administrated site in a defined period. PMID- 17269142 TI - Influence of TiO2 and Ag2O addition on tricalcium phosphate ceramics. AB - Degradation of implanted ceramics allows for bone in-growth and eventual replacement with natural tissue. Calcium phosphate-based materials have gained the most significant attention because of their excellent biocompatibility and compositional similarities to natural bone. Adding various dopants to these ceramics significantly influences critical properties. In this study, tricalcium phosphate (TCP) compacts were fabricated via uniaxial compression with four compositions: (i) pure TCP, (ii) TCP with 1.0 wt % TiO(2), (iii) TCP with 0.5 wt % Ag(2)O, and (iv) ternary of TCP and 1.0 wt % TiO(2), and 0.5 wt % Ag(2)O. These compacts were sintered at 1250 degrees C for 4 h to obtain dense ceramic structures. Phase analyses were carried out using an X-ray diffractometer. The presence of TiO(2) in TCP improved densification and increased compression strength from 70 (+/-25) to 145 (+/-40) MPa. The ternary composition had the highest density and compression strength of 180 (+/-15) MPa. Human osteoblast cell growth behavior was studied using an osteoprecursor cell line (OPC 1) to assure that the biocompatibility of these ceramics was not altered due to the dopants. For long-term biodegradation studies, density, weight change, surface microstructure, and uniaxial compression strength were measured as a function of time in a simulated body fluid (SBF). Weight gain in SBF correlated strongly with precipitation viewed in the inter-connected pores of the samples. After 3 months in SBF, a 35% drop in compression strength was noticed for pure TCP, but for doped compositions, no strength loss was noticed. PMID- 17269143 TI - Enhanced bone bonding of hydroxyapatite-coated titanium implants by electrical polarization. AB - Hydroxyapatite (HAp) coatings are applied to orthopedic and dental implants made of titanium (Ti) and its alloys in order to increase their bioactivities and to offset the mechanical weakness of HAp. We examined the in vivo effects of electrical polarization on the bone bonding of HAp-coated Ti. Polarized samples with a negatively or positively charged HAp-coated surface (N- or P-surface, respectively) were randomly implanted in the femora and tibiae of canines. As controls, nonpolarized HAp-coated Ti substrates with 0-surfaces were implanted. Direct bonding between the newly formed bone and HAp-coated Ti was observed with the O-, N-, and P-surfaces. The results of a pullout test were consistent with the amount of newly formed bone bonded directly to the surface of HAp-coated Ti. Electrically polarized HAp-coated Ti substrates, especially those with N surfaces, exposed to recipient bone enhance bone bonding and could enable earlier weight-bearing loads after operations. PMID- 17269144 TI - Pre-culture period of mesenchymal stem cells in osteogenic media influences their in vivo bone forming potential. AB - The objective of this study was to investigate if the in vitro pre-culture period in osteogenic media of rat mesenchymal stem cells (MSCs), influences their ability to regenerate bone when implanted in a critical size cranial defect. MSCs were harvested from the bone marrow of 6-8 weeks old male Fisher rats and expanded in vitro in osteogenic media for different time periods (4, 10, and 16 days) in tissue culture plates (TCP), seeded on sintered titanium fiber meshes without the extracellular matrix (ECM) generated in vitro, and implanted in the rat cranium after 12 h. Thirty two adult Fisher rats received the implants, divided in four groups. Three groups were implanted with cells cultured for 4, 10, or 16 days in osteogenic media and at that time their alkaline phosphatase activity and mineral deposition denoted that they were at different stages of their osteoblastic maturation (undifferentiated MSC, committed, and mature Osteoblasts, respectively). MSCs cultured without osteogenic media for 6 days were used as controls. The constructs were retrieved 4 weeks later and processed for histomorphometric analysis. Implants seeded with cells that have been cultured with osteogenic media for only 4 days revealed the highest bone formation. The lowest bone formation was obtained with the implants seeded with MSCs cultured for 16 days in the presence of osteogenic media. The results of this study suggested that the in vitro pre-culture period of MSCs is a critical factor for their ability to regenerate bone when implanted to an orthotopic site. PMID- 17269145 TI - Folate coupled poly(ethyleneglycol) conjugates of anionic poly(amidoamine) dendrimer for inflammatory tissue specific drug delivery. AB - Folate receptor is overexpressed on the activated (but not quiescent) macrophages in both animal models and human patients with naturally occurring rheumatoid arthritis. The aim of this study was to prepare folate targeted poly(ethylene glycol) (PEG) conjugates of anionic dendrimer (G3.5 PAMAM) as targeted drug delivery systems to inflammation and to investigate its biodistribution pattern in arthritic rats. Folate-PEG-PAMAM conjugates, with different degrees of substitution were synthesized by a two-step reaction through a carbodiimide mediated coupling reaction and loaded with indomethacin. Folate-PEG conjugation increased the drug loading efficiency by 10- to 20-fold and the in vitro release profile indicated controlled release of drug. The plasma pharmacokinetic parameters indicated an increased AUC, circulatory half-life and mean residence time for the folate-PEG conjugates. The tissue distribution studies revealed significantly lesser uptake by stomach for the folate-PEG conjugates, thereby limiting gastric-related side effect. The time-averaged relative drug exposure (r(e)) of the drug in paw for the folate-PEG conjugates ranged from 1.81 to 2.37. The overall drug targeting efficiency (T(e)) was highest for folate-PEG conjugate (3.44) when compared to native dendrimer (1.72). The folate-PEG-PAMAM conjugates are the ideal choice for targeted delivery of antiarthritic drugs to inflammation with reduced side-effects and higher targeting efficiency. PMID- 17269146 TI - Expression of core binding factor 1 and osteoblastic markers in C2C12 cells induced by calcium phosphate ceramics in vitro. AB - The in vivo osteoinductive capacity of porous calcium phosphate ceramics (Ca/P ceramics) with special structure and phase composition had been found for almost decades. The mechanism of the osteoinductivity of porous calcium phosphate is studied by C2C12 cells culture in this paper. C2C12 cells were cocultured with four kinds of porous Ca/P ceramics for 2 and 5 days, without adding other growth factors. The four kinds of Ca/P ceramics were pure HA sintered at 1250 degrees C and HA/TCP with a ratio of 60/40 sintered at 1100, 1200, and 1250 degrees C respectively. RT-PCR analysis found that the Ca/P ceramics induced the expression of Cbfa1, collagen type I, bone sialoprotein, and osteocalcin in C2C12 cells, while they did not induce mRNA expression of Indian hedgehog (IHH) that regulate chondrocyte differentiation. Our results showed that Ca/P ceramics alone were sufficient to induce C2C12 cells differentiation. The induction of bone-related markers expression by Ca/P ceramics in osteoprogenitor cells suggested that the osteogenesis induced by the ceramics was intramembranous and the osteoinductivity was their intrinsic property. PMID- 17269147 TI - Micromechanical bending of single collagen fibrils using atomic force microscopy. AB - A new micromechanical technique was developed to study the mechanical properties of single collagen fibrils. Single collagen fibrils, the basic components of the collagen fiber, have a characteristic highly organized structure. Fibrils were isolated from collagenous materials and their mechanical properties were studied with atomic force microscopy (AFM). In this study, we determined the Young's modulus of single collagen fibrils at ambient conditions from bending tests after depositing the fibrils on a poly(dimethyl siloxane) (PDMS) substrate containing micro-channels. Force-indentation relationships of freely suspended collagen fibrils were determined by loading them with a tip-less cantilever. From the deflection-piezo displacement curve, force-indentation curves could be deduced. With the assumption that the behavior of collagen fibrils can be described by the linear elastic theory of isotropic materials and that the fibrils are freely supported at the rims, a Young's modulus of 5.4 +/- 1.2 GPa was determined. After cross-linking with glutaraldehyde, the Young's modulus of a single fibril increases to 14.7 +/- 2.7 GPa. When it is assumed that the fibril would be fixed at the ends of the channel the Young's moduli of native and cross-linked collagen fibrils are calculated to be 1.4 +/- 0.3 GPa and 3.8 +/- 0.8 GPa, respectively. The minimum and maximum values determined for native and glutaraldehyde cross linked collagen fibrils represent the boundaries of the Young's modulus. PMID- 17269148 TI - Early gene expression analyzed by cDNA microarray and real-time PCR in osteoblasts cultured with chitosan monomer. AB - Chitosan has a variety of biological activities. Although it has been reported that chitosan promotes osteogenesis in bone lesions, little is known about how it modulates the hard tissue forming cells at the gene level. This study focused on gene expressions in osteoblasts cultured with a super-low concentration of chitosan monomer. cDNA probes were synthesized from isolated RNA and labeled with fluorescent dye. They were hybridized with Human 3.8 II cDNA microarray, and the fluorescent signal was analyzed. cDNA microarray analysis revealed that 10 genes concerning to various signaling-related molecules were expressed at > or =2.0 fold higher signal ratio levels in the experimental group when compared with the control group after 3 days. Real-time PCR analysis showed that chitosan monomer induced an increase in the expression of four signal transduction genes, mitogen activated protein kinase (MAPK)K3, MAPKKK11, Rac1 and Shc1, together with the alkaline phosphatase gene. These results suggest that a super-low concentration of chitosan monomer could modulate the activity of osteoblastic cells through mRNA levels and that chitosan monomer directly affects signal transduction inside cells. PMID- 17269149 TI - A physical vapor deposition method for controlled evaluation of biological response to biomaterial chemistry and topography. AB - The purpose of this study was to characterize a technique to effectively mask surface chemistry without modifying surface topography. A thin layer of titanium was deposited by physical vapor deposition (PVD) onto different biomaterial surfaces. Commercially pure titanium disks were equally divided into three groups. Disks were either polished to a mirror finish, grit blasted with alumina particles, or grit blasted and subsequently plasma sprayed with a commercial grade of hydroxyapatite (HA). A subgroup of each of these treatment types was further treated by masking the entire disk surface with a thin layer of commercially pure titanium deposited by PVD. A comparison of surface topography and chemical composition was carried out between disks within each treatment group. Canine marrow cells were seeded on all disk surfaces to determine the stability of the PVD Ti mask under culture conditions. The PVD process did not significantly alter the surface topography of any samples. The thin titanium layer completely masked the underlying chemistry of the plasma sprayed HA surface and the chemistry of the plasma vapor deposited titanium layer did not differ from that of the commercially pure titanium disks. Aliquots obtained from the media during culture did not indicate any significant differences in Ti concentration amongst the Ti and Ti-masked surfaces. The PVD application of a Ti layer on HA coatings formed a stable, durable, and homogenous layer that effectively masked the underlying surface chemistry without altering the surface topography. PMID- 17269150 TI - Centres of excellence: the Thoraxcenter. PMID- 17269151 TI - Viewpoint: Cardiology as a career for women. PMID- 17269152 TI - The promise of synthetic biology. AB - DNA synthesis has become one of the technological bases of a new concept in biology: synthetic biology. The vision of synthetic biology is a systematic, hierarchical design of artificial, biology-inspired systems using robust, standardized, and well-characterized building blocks. The design concept and examples from four fields of application (genetic circuits, protein design, platform technologies, and pathway engineering) are discussed, which demonstrate the usefulness and the promises of synthetic biology. The vision of synthetic biology is to develop complex systems by simplified solutions using available material and knowledge. Synthetic biology also opens a door toward new biomaterials that do not occur in nature. PMID- 17269153 TI - In vivo engineering of proteins with nitrogen-containing tryptophan analogs. AB - Recently, it has become possible to reprogram the protein synthesis machinery such that numerous noncanonical amino acids can be translated into target sequences yielding tailor-made proteins. The canonical amino acid tryptophan (Trp) encoded by a single nucleotide triplet (UGG) is a particularly interesting target for protein engineering and design. Trp-residues can be substituted with a variety of analogs and surrogates generated biosynthetically or by organic chemistry. Among them, nitrogen-containing tryptophan analogs occupy a central position, as they have distinct chemical properties in comparison with aliphatic amines and imines. They resemble purine bases of DNA and share their capacity for pH-sensitive intramolecular charge transfer. These special properties of the analogs can be directly transmitted into related protein structures via in vivo ribosome-mediated translation. Proteins expressed in this way are further endowed with unique properties like new spectral, altered redox and titration features or might serve as useful biomaterials. We present and discuss current works and future developments in protein engineering with nitrogen-containing tryptophan analogs and related compounds as well as their relevance for academic and applicative research. PMID- 17269154 TI - The mitochondrial compartment. AB - Mitochondria are vital organelles that perform a variety of fundamental functions ranging from the synthesis of ATP through to being intimately involved in programmed cell death. Comprised of at least six compartments: outer membrane, inner boundary membrane, intermembrane space, cristal membranes, intracristal space, and matrix, mitochondria have a complex, dynamic internal structure. This internal dynamism is reflected in the pleomorphy and motility of mitochondria. Mitochondria contain their own DNA (mtDNA), encoding a small number of vital genes, but this role as a genetic vault is not compatible with the role of mitochondria in bioenergetics since electron transport results in the generation of reactive oxygen species (ROS) that induce lesions in the mtDNA. It is hypothesized that ROS shape the morphological organization of the higher plant cell mitochondrial population into a discontinuous whole, and that ROS are a selective pressure affecting the organization of the mitochondrial genome. This review describes how inter- and intra-mitochondrial compartmentalization underpins the biology of this complex organelle. PMID- 17269155 TI - Erratum to "Safety of zonisamide therapy: prospective follow-up survey.". AB - Zonisamide safety was evaluated based on a postmarketing surveillance study of patients treated for 1-3 years. Nine hundred twenty-eight children and 584 adult (ages 1 month to 79 years), including 372 newly-diagnosed patients, received zonisamide for partial and generalized epilepsies. Of the intractable patients, 1088 received zonisamide in combination with other antiepileptic drugs (AED), and 52 successfully transitioned to zonisamide monotherapy. A total of 1089 adverse events occurred in 476 (31.5%) of 1512 patients. Incidence of adverse effects was significantly lower among patients receiving zonisamide monotherapy than in those receiving polytherapy: 21% (18.9% of children, 29.4% of adults) versus 35.6% (30.4% of children, 41.7% of adults), respectively. The total incidence of adverse effects was lower for children (26.2%) than for adults (39.9%). Most common adverse events included mental/psychiatric symptoms (19.4%), gastrointestinal symptoms (8.7%), and neurological symptoms (6.5%). Effects that seemed unique to zonisamide were impairment of mental function, motivation or volition, and hipohidrosis. Urinary calculi were detected in only two patients (0.13%). Teratogenicity was evaluated in six patients. Two patients on zonisamide monotherapy and three on polytherapy delivered normal children. One of four patients on polytherapy conceived a fetus with a skull defect with cerebral and cerebellar dysgenesis, namely anencephaly. PMID- 17269156 TI - Five years on...and four challenges for the pharmaceutical industry. PMID- 17269157 TI - Pharma faces major challenges after a year of failures and heated battles. PMID- 17269158 TI - A call to arms. PMID- 17269159 TI - The antibacterial drugs market. PMID- 17269160 TI - Vorinostat. PMID- 17269161 TI - A new top-down proteomics workflow. PMID- 17269163 TI - Test standards for proteomics: multiple choices. PMID- 17269162 TI - Quantitating peptide-protein interactions. PMID- 17269164 TI - Mass thickness determination and microanalysis of thin films in the TEM- revisited. AB - Calibrating on a series of thicknesses of a single element we arrive at a simple method of mass thickness determination for amorphous and polycrystalline films in the transmission electron microscopy (TEM). The conditions to be fulfilled are: acceleration voltage 200 kV or higher and measuring the integrated transmitted electron intensity in a wide range of angles that contains also the Bragg reflections. Under these conditions the electron scattering depends on Z2 as predicted by the Rutherford approximation. There is no need to carry out a calibration for atomic number dependence. For multicomponent films of unknown composition the combination of electron and X-ray intensity measurement results in absolute (non-normalized) concentrations and the value of local mass thickness. Examples of quantitative analysis are presented and an extension to single crystal films is discussed. PMID- 17269165 TI - New technologies against food pathogens. PMID- 17269166 TI - [Tungiasis (Tunga penetrans)]. PMID- 17269167 TI - Embryonic-like stem cells from umbilical cord blood and potential for neural modeling. AB - Stem cells offer the distinct prospect of changing the face of human medicine. However, although they have potential to form different tissues, are still in the early stages of development as therapeutic interventions. The three most used stem cell sources are umbilical cord blood, bone marrow and human embryos. Whilst, cord blood is now used to treat over 70 disorders, at the time of writing this manuscript, not a single disease has been overcome or ameliorated using human embryonic stem cells. Advancing stem cell medicine requires ethically sound and scientifically robust models to develop tomorrow's medicines. Media attention, however, distracts from this reality; it is important to remember that stem cells are a new visitor to the medical world and require more research. Here we describe the utility of human cord blood to develop neural models that are necessary to take stem cells to the next level--into human therapies. PMID- 17269168 TI - Thinking gender with sexuality in 1790s feminist thought. PMID- 17269169 TI - Creating a veil of silence? Politeness and marital violence in the English household. PMID- 17269170 TI - "Matrimonial ceremonies displayed": popular ethnography and enlightened imperialism. PMID- 17269171 TI - Matrix of modernity? The Colin Matthew memorial lecture. PMID- 17269172 TI - Topographies of politeness. PMID- 17269173 TI - Abstracts of the Annual Symposium of Transcatheter Cardiovascular Therapeutics, October 22-27, 2006, Washington, DC, USA. PMID- 17269174 TI - Orthopaedic proceedings, 2003-2006. PMID- 17269175 TI - Threatened wombs: aspects of ancient uterine magic. PMID- 17269176 TI - Effect of ramipril on the incidence of diabetes. PMID- 17269177 TI - Abstracts of the Annual Meeting of the American College of Allergy, Asthma and Immunology and the 12th International Food Allergy Symposium, November 9-15, 2006, Philadelphia, Pennsylvania, USA. PMID- 17269178 TI - Prevention of meningococcal disease. PMID- 17269179 TI - Chest 2006, October 21-26, 2006, Salt Lake City, Utah, USA. Abstracts. PMID- 17269180 TI - Abstracts of the 22nd IUSTI-Europe Conference on Sexually Transmitted Infections, 19-21 October 2006, Versailles, France. PMID- 17269181 TI - Case 32-2006: a girl with fever after a visit to Africa. PMID- 17269182 TI - Abstracts of the 6th International Symposium on Mass Spectrometry in the Health and Life Sciences: Molecular and Cellular Proteomics, August 21-25, 2005, San Francisco, California, USA. PMID- 17269183 TI - Epithelial anion transport in health and disease: the role of the SLC26 transport family. Proceedings of a symposium, March 1-3, 2005. London, United Kingdom. PMID- 17269184 TI - Abstracts of the Swiss Society for Anaesthesiology and Reanimation, Interlaken, Switzerland, November 2-4, 2006. PMID- 17269185 TI - [De pulsibus ad tirones: Galen and new physicians: the pulse as a means of diagnosis and prognosis]. PMID- 17269186 TI - [Patient information. Hereditary hemochromatosis]. PMID- 17269187 TI - Denosumab in postmenopausal women with low bone mineral density. PMID- 17269189 TI - [Some aspects of Rhazes' ethics and their origins in the works of Galen]. PMID- 17269188 TI - The diagnostic "gold standard" in oncology: increasing importance and increasing concerns. PMID- 17269190 TI - [Some aspects of Rhaze's ethics and their origins in the works of Galen]. PMID- 17269191 TI - [The professionalization of the Greek physician and the Hippocratic Oath]. PMID- 17269192 TI - [Traces of an ancient Latin canon of Hippocrates and Galen]. PMID- 17269193 TI - [Hepatitis B vaccine]. PMID- 17269194 TI - [Traces of an ancient Latin canon of Hippocrates and Galen]. PMID- 17269195 TI - Early dental appliances in the Eastern Mediterranean. PMID- 17269196 TI - [The problem of knowledge in Galen's De optima doctrina]. PMID- 17269197 TI - New light on the patria of Arnald of Villanova. PMID- 17269198 TI - [Eating and drinking by the Greeks and Romans]. PMID- 17269199 TI - Western medical thought from antiquity to the Middle Ages. PMID- 17269200 TI - Kyathos at Aristophanes, Pax, 538-542; Lysistrata, 443-444 and [Aristotle] Problems, 890b7-38. PMID- 17269201 TI - Two 'sets' of Roman surgical tools from the Holy Land. PMID- 17269202 TI - Medico-philosophical controversies in Nathan b. Jo'el Falaquera Sefer Zori ha Guf. PMID- 17269203 TI - Baladhur (marking-nut): a popular medieval drug for strengthening memory. PMID- 17269204 TI - Ibn al-Jazzar on medicine for the poor and destitute. PMID- 17269205 TI - The Spine Files: Spine in the Arts. Hermes of Praxiteles--preservation of motion and realism. PMID- 17269206 TI - Faces of Spine Care: From the Clinic and Imaging Suite. Klippel-Feil syndrome and associated abnormalities: the necessity for a multidisciplinary approach in patient management. PMID- 17269207 TI - On editing and translating Medieval Hebrew medical manuscripts. PMID- 17269208 TI - Lentiviral vectors for gene therapy of heart disease. AB - Technological advances in genetic engineering developed over the past few years have been applied to the research and treatment of cardiovascular diseases. In many animal models, gene therapy has been shown to be an effective treatment schema. Some of these gene therapy treatments are now being applied in clinical trials. Also, as the science of gene therapy has progressed, alternative vector systems such as lentiviruses have been developed and implemented. Here we focus on the emerging role of lentiviral vectors in the treatment of cardiovascular disease. PMID- 17269209 TI - Pathogenesis of acute myocardial infarction in young male adults with or without obesity. AB - OBJECTIVES: Obesity may be linked with coronary atherosclerosis in young males. This study investigated the etiology of acute myocardial infarction (AMI) in young Japanese male patients with or without obesity. METHODS AND RESULTS: This retrospective study included 2,230 AMI patients enrolled in the AMI-Kyoto Multi Center Risk Study between January 2000 and December 2005. Clinical background, risk factors, angiographic findings, acute results of primary percutaneous coronary intervention (PCI), and in-hospital outcome were evaluated in 33 young male patients < 40 years old. The study group was divided into the obese group [body mass index (BMI) > or =25, n=21] and non-obese group (BMI < 25, n=12). Four of the 12 non-obese patients had underlying disease (Kawasaki disease 2, Buerger's disease 1, drug abuse 1). The non-obese group had a higher prevalence of underlying disease than the obese group. The non-obese group had a higher incidence of left anterior descending coronary artery as culprit lesion and higher Thrombolysis in Myocardial Infarction (TIMI) grade flow in the infarct related artery before primary PCI. The acquisition rates of TIMI 3 flow after primary PCI and in-hospital outcome did not differ between the two groups. CONCLUSIONS: Non-obese young AMI male patients have a higher frequency of underlying disease. Most young male AMI patients were obese, suggesting that obesity may be important in the pathogenesis of AMI in young male adults. PMID- 17269210 TI - Effect of renal transplantation on the cardiac function of patients with hemodialysis. AB - OBJECTIVES: This study investigated whether renal transplantation could improve cardiac function in patients who had undergone hemodialysis. METHODS: Cardiac function and coronary risk factors were compared between the renal transplantation group (RT group: n=34) and the maintenance hemodialysis group (HD group: n=40). The dialysis period was also evaluated. RESULTS: Anemia and electrolyte disorders significantly improved in the RT group compared to the HD group. However, both groups required therapy for coronary risk factors. Cardiac function in the RT group was better than in the HD group. CONCLUSIONS: Disorders of cardiac function caused by chronic renal failure or the introduction of hemodialysis tended to improve after renal transplantation. Moreover, disorders of cardiac function seemed to improve more rapidly in patients in the RT group who had undergone hemodialysis for shorter periods prior to renal transplantation. PMID- 17269211 TI - [Association between occurrence of acute myocardial infarction and meteorological factors]. AB - OBJECTIVES: The association between the occurrence of acute myocardial infarction and meteorological factors was examined in five cities of the Chugoku area in Japan. METHODS: This study used the emergency admission data for acute myocardial infarction in Yamaguchi, Matsue, Tottori, Okayama (from April 2000 to March 2005), and Hiroshima (from January 1993 to December 2002). Daily meteorological data was obtained from The Japan Meteorological Agency. The Poisson regression model was used to examine the association between acute myocardial infarction and daily average temperature and pressure. RESULTS: In Hiroshima, Okayama, Yamaguchi and Matsue City, daily average events of acute myocardial infarction were 30%, 30%, 33% and 40% higher in winter than those in summer (p < 0.05). Daily average events increased as atmospheric temperature decreased. In Hiroshima, Okayama and Yamaguchi City, daily average events in the low temperature group (T < 10 degrees C) were significantly higher than those in the high temperature group (T > or =20 degrees C) (p < 0.05). In Hiroshima City, a significant interaction was found between temperature and pressure. Daily events in the low temperature and low pressure group (1.38/day) was significant and 37% larger than in the high temperature and moderate pressure group (0.94/day; risk ratio = 1.37, 95% confidence interval 1.01-1.86, p < 0.05). Days with low temperature and low pressure were characterized by rain and/or snow. CONCLUSIONS: The occurrence of acute myocardial infarction was associated with low temperatures, especially daily average temperature lower than 10 degrees C. The risk was high on days with low temperature and low pressure in Hiroshima City. PMID- 17269212 TI - [Shock during spasm provocation tests with acetylcholine: four case reports]. AB - Four patients suffered shock during the spasm provocation test with acetylcholine. An 84-year-old man with acute coronary syndrome was treated with stent implantation in the mid left anterior descending artery. Before discharge, acetylcholine test demonstrated coronary spasm in both the proximal left anterior descending artery and proximal left circumflex artery. A 61-year-old woman was admitted to the hospital because of recurrent rest and effort chest pain. Coronary arteriography showed no significant stenosis but shock was observed by intracoronary injection of acetylcholine due to diffuse severe coronary vasospasm in the proximal left anterior descending artery and left circumflex artery. Shock occurred in 4 of 1110 (0.36%) consecutive acetylcholine tests. Coronary spasm was gradually relieved and recovered from shock by the intraarterial administration of small amounts of norepinephrine and isosorbide dinitrate. Although the acetylcholine spasm provocation test is safe and reliable, care is required even during a selective procedure. PMID- 17269213 TI - [Postgastrectomy beriberi exaggerated by diuretic use: a case report]. AB - A 66-year-old male was referred to our hospital because of severe pitting edema in the lower extremities in April 2003. He had undergone a partial gastrectomy for gastric cancer 17 years before and radiotherapy for oropharyngeal cancer 1 year before. He had suffered from the edema for 4 years. Loop diuretics prescribed by his family doctor were effective for relieving the edema at first, but the edema was not resolved. He was hospitalized with evidence of hypothyroidism from blood analysis. Administration of levothyroxin partially relieved the edema, but loop diuretics were continued because the edema was not completely diminished. He was admitted to our hospital again in October 2003, because of unsteady gait and worsened edema. Neurological examination revealed the stocking-and-glove pattern of sensory disturbance and distal muscle weakness in the lower extremities. Plasma vitamin B1 (thiamine)concentration was low, and the diagnosis was beriberi. After vitamin B, supplementation was initiated, the patient's edema completely disappeared in a few days, and his gait disturbance gradually subsided. Diuretics lead to increased urinary vitamin B1 excretion, so we should be watchful for thiamine deficiency in patients treated with diuretics who underwent gastrectomy and potentially have latent vitamin B1 deficiency. PMID- 17269214 TI - Adenosine stress thallium-201 myocardial scintigraphy. PMID- 17269215 TI - Malaria in Colombia: retrospective glance during the past 40 years. AB - OBJECTIVE: Describe and analyze the structural configuration of malaria in Colombia since 1960 to 2004 where the phenomena of persistence, resurgence and resistance as well as the main determinants associated to these phenomena. METHODS: A comparative study of the history of malaria and its trend was conducted in Colombia since 1960-2004. Secondary and primary information about the frequency and spatial distribution of malaria was collected. The sub period were identified according to institutional transformation and malaria control strategies as well as the socioeconomic and sociopolitical conjuncture factors in the country. RESULTS: The structural and situational analyses of malaria in Colombia shown a steadily increase in morbidity from an average API 2,19 x 1 000 in 1960-74 to 8,92 by 1994-2004. Since the middle 70's there has been a considerable reduction of mortality. The malaria case relation P. vivax vs. P. falciparum is 3 to 5, respectively. The Annual Positive Sample Rate increased during the same study periods from 3.96% to 29.93%. Unfortunately the Annual Blood Examination Rate-ABER decreased by fewer than 5%, instead of increase to minimum required for detection of malaria. CONCLUSIONS: During the National Eradication Malaria Service the malaria decreased steadily by the first five years, unfortunately the disease present resurgence, persistence after the reduction of financial and technical support from international health agencies in the middle seventies. Nowadays, around 85% of the territory, mainly rural areas are endemic for malaria. In spite of the transformation of the health system and different strategies implemented against malaria, it continues being one of the priorities in the public health services of Colombia. PMID- 17269216 TI - [Knowledge, opinions and experience from applying health participation policy in Colombia]. AB - OBJECTIVE: Analysing knowledge and opinions regarding policies related to social participation in health and how user, community leader and health personnel participation mechanisms are used in Colombia. METHODS: An exploratory and descriptive study was carried out between 1999 and 2001 in the towns of Tulua and Palmira in Colombia using a combination of research methods. A sample of 1,497 health care users were formally surveyed, a focus-group-based qualitative study was made of 210 users and 40 community leaders and 36 semi-structured individual interviews were conducted with health personnel. SPSS was used for a descriptive analysis of survey data and Ethnograph for narrative content analysis of qualitative data. RESULTS: The user survey results revealed a lack of knowledge regarding norms and mechanisms for social participation in health, as well as limited use. Limited knowledge and scepticism regarding its effectiveness was also reflected in the users, leaders and health personnel qualitative study results. Public sector personnel, however, displayed better knowledge and referred to greater implementation of participation mechanisms. Lack of both resources and a culture of participation were amongst the difficulties faced in implementing it. CONCLUSIONS: The results indicated scarce knowledge and little use of social participation in health mechanisms (market-based ones predominating). Much greater investment in information and training the population and health system personnel is required as a first step towards promoting real social participation for social control of the health system. PMID- 17269217 TI - [Evaluating the "it's better if we talk" (Mejor Hablemos) communication strategy for promoting pacific co-existence in Cali, Colombia, between 1996-2000]. AB - OBJECTIVE: Evaluating the "It's better if we talk" communication strategy for preventing violence and promoting pacific coexistence in Cali, Colombia. MATERIALS AND METHODS: The strategy was developed through two intervention components in Cali between August 1996 and September 1998: the population (using the mass media) and the community (using Commune 13 and 20's local media). Post intervention measurement was made in 2000 to determine the strategy's impact and compared to PAHO's 1996 ACTIVA base-line study carried out in eight Latin American cities (including Cali) and Spain. 3 types of analysis were used: descriptive-comparative between the periods and bivariate and multivariate analysis using attitudes and abilities as dependent variables. RESULTS: Abilities improved at population level, although they did not change in the communes taking part. Favourable changes occurred in attitudes in community areas, though remaining equal at population level. The mechanisms for solving conflicts displayed an improvement, suggesting increased tolerance from 1996 to 2000 in older men from Commune 20 and the rest of Cali. DISCUSSION: "It's better if we talk" had little impact on the community areas taking part; nevertheless, the universal intervention had a positive impact on the rest of Cali. Interdisciplinary, ongoing multi-sector promotion and prevention must be embarked on for approaching the multifactor problem of violence in Latin-American countries involving individuals and their family, community and institutional governmental contexts. PMID- 17269218 TI - [Cervical cytology in Soacha, Colombia: social representation, barriers and motivation]. AB - OBJECTIVE: A social representation of the Pap smear is given in this article, as are the barriers against it and the motivation for practising it, aimed at adjusting preventative health services in a particular Colombian town. METHODS: A phenomenological, qualitative study was carried out, using focal groups and workshops for validating the results. A theoretical sample was designed to find differences according to age, heatlh system affiliation and dwelling place within the municipality in question. Atlas ti software was used for giving the analysis a narrative interpretation. RESULTS: The Pap smear is associated with infection and pre-cancer and cancer prevention. Cultural barriers, misinformation being spread by peers, a lack of social networks and the particularly poor quality of Colombian public health services were identified. DISCUSSION: Attempts to make the Pap smear as objective as possible were found to be satisfactory, even though no logical relationship was found between knowledge of the Pap smear and its practice. Older women have the social representation of risk implicit in an acute infection model. Lack of opportunity for a having a Pap smear appointment and delays in presenting the corresponding report have a negative impact on cancer control. PMID- 17269219 TI - [Displaced people's healthcare use in Bucaramanga, Colombia]. AB - OBJECTIVE: Analysing the factors and barriers associated with the population displaced by armed conflict using medical services in Bucaramanga, Colombia. MATERIAL AND METHODS: Data from the "Diagnosing the health of both displaced and non-displaced populations in Bucaramanga and its metropolitan area" study, designed and executed by the Industrial University of Santander and financed by the Pan-American Health Organisation, analysed medical service use in individuals aged over 15 years. This agreed with Andersen and Newman's model and evaluated the effect of associated factors by means of multiple logistical regression. RESULTS: One out of each five people who became ill during the fifteen days prior to the survey had used the medical services. This percentage was smaller than that found in the Colombian population as a whole. The type of social security regime (contributory health insurance), previous service use and being from the region were associated with greater service use. Displaced people having subsidised health insurance did not present differences in service use compared to those who had no access to such insurance. The distance from dwelling to institution was another barrier against using health services (RM = 0.64; IC 0.42 0.97). CONCLUSIONS: There was differential medical service use amongst the displaced population, determined by their health insurance coverage and economic position. PMID- 17269220 TI - [Dental caries amongst mentally retarded people and those suffering from Down's syndrome]. AB - OBJECTIVE: A descriptive investigation was conducted for determining the prevalence of dental caries amongst mentally retarded (MR) people and those suffering from Down's syndrome (DS). METHODS: A special school located in Moran county in the State of Lara was visited. The inclusion criteria involved dental examination of 60 students and their parents/or the person responsible for them being interviewed. RESULTS: Participants' mean age was 14.5 +/- 8.17; 48.3% were from a blue collar level. Regarding oral health, 53.0% had dental caries, 51.7% being in the molars. Moderately MR people had the highest proportion of dental caries (75%). About 53% of the females and 46.2% of males, 644% and 31.9% of RM and DS participants had caries. 28.3% needed non-urgent dental treatment and 45% were using public dental health services. CONCLUSIONS: People suffering from MR and DS have precarious oral health; it is thus recommended that health programmes be created which are specifically directed towards these people. PMID- 17269221 TI - [Choice of and preference for home child-birth in Callao, Peru]. AB - OBJECTIVE: Identifying the personal factors and prenatal attention associated with choosing the home for giving birth. MATERIAL AND METHODS: The study included 52 cases (fertile women whose last childbirth had been at home) and 208 controls (fertile women residing in the same geographical area). The study was carried out in the Pachacutec micro-network. Analysis was both bivariate and multivariate. RESULTS: The cases' average age was 28 (6,5 SD) and 26 for controls (6,1 SD). Bivariate analysis demonstrated a significant association for different factors but these they were not confirmed when multivariate analysis was applied. The risk factors were the home as foreseen place for childbirth w = 34.8 (p = 0.0); OR = 31.7 (CI = 10.1; 99.8) and prenatal attention supplier w = 7.0 (p = 0.0); OR = 0.1 (CI = 0.0; 0.5). CONCLUSIONS: The home as foreseen place for childbirth and prenatal attention supplier were the factors which were highly associated with home childbirth. PMID- 17269222 TI - [Clinical practice in looking after breastfeeding women and the new-born in some hospitals in Bogota, Colombia]. AB - OBJECTIVE: Evaluating the frequency of 17 practices being used in managing the main causes of maternal and perinatal morbidity and mortality in some hospitals in Bogota between August 2004 and March 2005. METHODS: A cross-sectional study was carried out. The data related to 3,108 women who gave birth at gestational age greater than 24 weeks. RESULTS: The following percentages were obtained for each variable evaluated: having a perinatal record card (79.4%), taking iron and folic acid supplement (87.3%), syphilis screening (69.5%), bacteriuria screening (69.7%), constant accompaniment during giving birth (42.0%), not taking enemas (99.4%), not shaving the perinea (93.0%), selective episiotomy in first-time mothers (56.5%), adopting a squatting or seated position when giving birth (7.9%), active management of birth in gestation greater than 41 weeks (14.7%), active management of birth (73.5%), administering prophylactic antibiotics during a caesarean birth (61.2%), treating severe pre-eclampsia (76.5%) and eclampsia (20.0%) with magnesium sulphate, administering corticoids for inducing foetal maturation in mothers having a high risk of predetermined birth (51.6%), exclusive maternal lactation, having no restrictions (99.1%) and joint mother newborn accommodation (91.2%). CONCLUSIONS: Effective methodologies are required for guaranteeing adherence to maternal and perinatal attention regulations and guidelines and those administrative and management decisions facilitating compliance with them. PMID- 17269223 TI - [Self-care agency ability in people suffering from high blood pressure hospitalised in Bogota, Colombia]. AB - OBJECTIVE: Describing how hospitalised people who have been diagnosed as having high blood pressure carry out self-care activities. METHODOLOGY: A descriptive design, having a quantitative approach, was used for evaluating the self-care agency ability of 90 people who had been hospitalised in Bogota diagnosed as suffering from high blood pressure. Evers and Isenberg's SAA (self-care agency appreciation) scale was used. RESULTS: The results showed that 53% of people hospitalised suffering from high blood pressure had deficient SAA. Regarding the SAA instrument's items obtaining the highest scores, it was found that the participants were able to maximise attention and vigilance, had motivation or self-care-orientated goals, reasoned within a self-care reference framework, had self-care abilities (cognitive, perception, communication and interpersonal) and integrated self-care operations with other aspects of life. CONCLUSION: Caring for hypertense people is a challenge for health-care personnel and the whole community. Nursing care should focus on helping individuals to look after themselves, engage in self-care action for conserving their health and lives, recover from illness and confront its consequences. PMID- 17269224 TI - [Use and determinants of Pap smear in a rural Colombian municipality 1998-1999]. AB - OBJECTIVES: Determining the prevalence of Pap smear use and identifying the factors associated with Pap test performance. METHODS: A cross-sectional study was carried out on volunteer women recruited from a local programme for detecting cervical cancer in Mogotes, Colombia. Prevalence ratios (PR) were calculated. Papanicolau smear use was the outcome being measured. Information about demographic characteristics, clinical factors, history of cancer in the family, lifestyle factors and using birth control methods was collected. RESULTS: Pap smear use prevalence was 67.3%. Age group, using birth control methods (PR: 1.4; 95% CI: 1.2-1.7) and living in rural settings (PR: 0.9; 95% CI: 0.8-1.0) were the factors associated with Pap test performance. CONCLUSIONS: This data suggests that living in rural settings is associated with decreased opportunities for performing Pap tests. PMID- 17269225 TI - Use of n-fold cross-validation to evaluate three methods to calculate heavy truck annual average daily traffic and vehicle miles traveled. AB - Reliable estimates of heavy-truck volumes in the United States are important in a number of transportation applications including pavement design and management, traffic safety, and traffic operations. Additionally, because heavy vehicles emit pollutants at much higher rates than passenger vehicles, reliable volume estimates are critical to computing accurate inventories of on-road emissions. Accurate baseline inventories are also necessary to forecast future scenarios. The research presented in this paper evaluated three different methods commonly used by transportation agencies to estimate annual average daily traffic (AADT), which is used to determine vehicle miles traveled (VMT). Traffic data from continuous count stations provided by the Iowa Department of Transportation were used to estimate AADT for single-unit and multiunit trucks for rural freeways and rural primary highways using the three methods. The first method developed general expansion factors, which apply to all vehicles. AADT, representing all vehicles, was estimated for short-term counts and was multiplied by statewide average truck volumes for the corresponding roadway type to obtain AADT for each truck category. The second method also developed general expansion factors and AADT estimates. Truck AADT for the second method was calculated by multiplying the general AADT by truck volumes from the short-term counts. The third method developed expansion factors specific to each truck group. AADT estimates for each truck group were estimated from short-term counts using corresponding expansion factors. Accuracy of the three methods was determined by comparing actual AADT from count station data to estimates from the three methods. Accuracy of the three methods was compared using n-fold cross-validation. Mean squared error of prediction was used to estimate the difference between estimated and actual AADT. Prediction error was lowest for the method that developed separate expansion factors for trucks. Implications for emissions estimation using the different methods are also discussed. PMID- 17269226 TI - Laboratory and field evaluation of crystallized DOW 704 oil on the performance of the Well Impactor Ninety-Six fFine particulate matter fractionator. AB - Subsequent to the 1997 promulgation of the Federal Reference Method (FRM) for monitoring fine particulate matter (PM2.5) in ambient air, U.S. Environmental Protection Agency (EPA) received reports that the DOW 704 diffusion oil used in the method's Well Impactor Ninety-Six (WINS) fractionator would occasionally crystallize during field use, particularly under wintertime conditions. Although the frequency of occurrence on a nationwide basis was low, uncertainties existed as to whether crystallization of the DOW 704 oil may adversely affect a sampling event's data quality. In response to these concerns, EPA and the State of Connecticut Department of Environmental Protection jointly conducted a series of specialized tests to determine whether crystallized oil adversely affected the performance of the WINS fractionator. In the laboratory, an experimental setup used dry ice to artificially induce crystallization of the diffusion oil under controlled conditions. Using primary polystyrene latex calibration aerosols, standard size-selective performance tests of the WINS fractionator showed that neither the position nor the shape of the WINS particle size fractionation curve was substantially influenced by the crystallization of the DOW 704 oil. No large particle bounce from the crystallized impaction surface was observed. During wintertime field tests, crystallization of the DOW 704 oil did not adversely affect measured PM2.5 concentrations. Regression of measurements with crystallized DOW 704 versus liquid dioctyl sebacate (DOS) oil produced slope, intercept, and R2 values of 0.98, 0.1, and 0.997 microg/m3, respectively. Additional field tests validated the use of DOS as an effective impaction substrate. As a result of these laboratory and field tests, DOS oil has been approved by EPA as a substitute for DOW 704 oil. Since the field deployment of DOS oil in 2001, users of this alternative oil have not reported any operational problems associated with its use in the PM2.5 FRM. Limited field evaluation of the BGI very sharp cut cyclone indicates that it provides a viable alternative to the WINS fractionator. PMID- 17269227 TI - Field demonstration of visible opacity photographic systems. AB - The Digital Opacity Compliance System (DOCS) is an innovative method that uses digital imaging technology to quantify visible opacity of stationary sources. DOCS, which has been demonstrated at pilot and full scale as a technically defensible and economically attractive alternative to U.S. Environmental Protection Agency (EPA) Reference Method 9 (Method 9), uses commercial-off-the shelf (COTS) digital cameras in combination with a user-friendly computer software package to determine opacity. To date, all DOCS field testing has been conducted using two models of digital cameras, notably, Kodak Models DC265 and DC290, both of which are no longer commercially available. To ensure that field validated digital cameras will be available to future DOCS users, a suite of new digital cameras was evaluated with the opacity determination software including the following: (1) Sony Model Cybershot Model DSC-WI, (2) Nikon Model Coolpix 5200, (3) Fuji Finepix Model E500, and (4) Kodak Model DX6490. Within the opacity range of regulatory interest, that is, 0-40%, the Sony Cybershot Model DSC-WI and Nikon Coolpix Model 5200 digital cameras were found to generate plume photographs of which the DOCS opacity analysis yielded results that were statistically equivalent to the previously field-validated Kodak Model DC290. In contrast, the Fuji Finepix Model E500 generated plume photographs of which the DOCS opacity analysis were, on average, 2.2% less than those generated by the Kodak Model DC290 photographs, a difference that was determined to be statistically significant. Over the same opacity range, photographs taken by the Kodak Model DX6490 yielded DOCS opacity readings that were found to be statistically equivalent to a Method 9-certified transmissometer. Based on the results from the current digital camera validation testing approach, EPA has developed a new camera-based visible opacity measurement method titled "Determination of Visible Emission Opacity from Stationary Sources Using Computer-Based Photographic Analysis Systems." The proposed method is expected to be promulgated after closure of the public comment period. PMID- 17269228 TI - Biodegradation of organic matters from mixed unshredded municipal solid waste through air convection before landfilling. AB - Landfilling is a dominant municipal solid waste (MSW) disposal method in most developing countries. In China, approximately 85% of the generated MSW is being disposed of in the landfills. The amount of MSW is growing rapidly with the rate of approximately 8-10% annually, which contains a high quantity of moisture and organic matters. The problems of leachate treatment and landfill gas (LFG) emissions are increasing gradually. Reducing the hazard before emplacement, pretreatment of MSW before landfilling has become very important for the conventional landfill. In this study, aerobic pretreatment of mixed MSW was used, and much attention has been given to the natural convection of air in the mixed and unshredded MSW for bioconversion of organic matter (OM). This study is an attempt to investigate aerobic pretreatment suitability for the mixed and unshredded MSW at Beijing. A pilot-scale aerobic pretreatment simulator (APS) was developed at Beishen Shu Landfill in Beijing. To work out the biodegradation of the OM in the APS, fresh and pretreated MSW samples were collected and analyzed for OM, moisture content, temperature, chemical oxygen demand, total organic carbon, carbon, nitrogen, hydrogen, lignocelluloses, and biochemical methane potential at various stages of the pretreatment. Furthermore, results of the fresh and pretreated MSW are compared. Significant reduction in the observed parameters of the pretreated waste samples is observed. This work demonstrates that pretreatment is significantly effective in reducing the landfill emissions that is leachate and LFG. PMID- 17269229 TI - Effects of CH4 and CO on the reduction of nitric oxide to nitrogen in a discharge reactor. AB - Additives are often added to enhance the efficiency of NO removal. This study uses a radio frequency (rf) discharge to consider the effect of added CH4 and CO to simulated NO/N2/O2/H2O mixtures on the elevation of NO conversion and the reduction of NO into N2. The enhancement levels of NO conversion when using various additives were found to be in this order: +CH4 > +CO > no additive. NO conversion reached 99.3%, 86.2%, and 77.6% when adding CH4, CO, and without additive, respectively, at inlet additive/NO molar ratio (R) = 5 and at 120 W. Moreover, the fraction of total N atoms converted from NO into N2 (FN2) was very high, reaching 99.4% and 99.5% when adding CH4 and CO, respectively, at R = 1 and at 120 W. The better operating conditions are using CH4 as the additive at R > or = 1 and a power of > 60 W to reach a higher NO conversion with a higher FN2. However, it should be noted that this rf plasma approach is not practical at this stage because of its relative low pressure. PMID- 17269230 TI - Gas chromatographic analysis of organic marker compounds in fine particulate matter using solid-phase microextraction. AB - A gas chromatographic method that uses solid-phase microextraction for analysis of organic marker compounds in fine particulate matter (PM2.5) is reported. The target marker compounds were selected for specificity toward emission from wood smoke, diesel or gasoline combustion, or meat cooking. Temperature-programmed volatilization analysis was used to characterize the thermal stabilities and volatile properties of the compounds of interest. The compounds were thermally evaporated from a quartz filter, sorbed to a solid phase microextraction (SPME) fiber, and thermally desorbed at 280 degrees C in a gas chromatograph injection port connected via a DB 1701 capillary separating column. Various experimental parameters (fiber type, time, and temperature of sorption) were optimized. It was found that high extraction yield could be achieved using a polyacrylate fiber for polar substances, such as levoglucosan, and a 7-microm polydimethylsiloxane (PDMS)-coated fiber for nonpolar compounds, such as hopanes and polyaromatic hydrocarbon. A compromise was made by selecting a carboxen/PDMS fiber, which can simultaneously extract all of the analytes of interest with moderate-to-high efficiency at 180 degrees C within a 30-min accumulation period. The optimized method was applied to the determination of levoglucosan in pine wood combustion emissions. The simplicity, rapidity, and selectivity of sample collection with a polymer-coated SPME coupled to capillary gas chromatography (GC) made this method potentially useful for atmospheric chemistry studies. PMID- 17269231 TI - A comparison between sludge ash and fly ash on the improvement in soft soil. AB - In this study, the strength of soft cohesive subgrade soil was improved by applying sewage sludge ash as a soil stabilizer. Test results obtained were compared with earlier tests conducted on soil samples treated with fly ash. Five different proportions of sludge ash and fly ash were mixed with soft cohesive soil, and tests such as pH value, compaction, California bearing ratio, unconfined compressive strength (UCS), and triaxial compression were performed to understand soil strength improvement because of the addition of both ashes. Results indicate that pH values increase with extending curing age for soil with sludge ash added. The UCS of sludge ash/soil were 1.4-2 times better than untreated soil. However, compressive strength of sludge ash/soil was 20-30 kPa less than fly ash/soil. The bearing capacities for both fly ash/soil and sludge ash/soil were five to six times and four times, respectively, higher than the original capacity. Moreover, the cohesive parameter of shear strength rose with increased amounts of either ash added. Friction angle, however, decreased with increased amounts of either ash. Consequently, results show that sewage sludge ash can potentially replace fly ash in the improvement of the soft cohesive soil. PMID- 17269232 TI - Dilution-based emissions sampling from stationary sources: Part 1--Compact sampler methodology and performance. AB - This paper presents the design and performance of a compact dilution sampler (CDS) for characterizing fine particle emissions from stationary sources. The sampler is described, along with the methodology adopted for its use. Dilution sampling has a number of advantages, including source emissions that are measured under conditions simulating stack gas entry and mixing in the ambient atmosphere. This is particularly important for characterizing the semivolatile species in effluents as a part of particulate emissions. The CDS characteristics and performance are given, along with sampling methodology. The CDS was compared with a reference dilution sampler. The results indicate that the two designs are comparable for tests on gas-fired units and a diesel electrical generator. The performance data indicate that lower detection limits can be achieved relative to current regulatory methods for particulate emissions. Test data for the fine particulate matter (PM2.5) emissions are provided for comparison with U.S. Environment Protection Agency (EPA) Conditional Test Method 040 for filterable particulate matter (FPM) and the EPA Method 202 for condensable particulate matter. This comparison showed important differences between methods, depending on whether a comparison is done between in situ FPM determinations or the sum of such values with condensable PM from liquid filled impingers chilled in an ice bath. These differences are interpretable in the light of semivolatile material present in the stack effluent and, in some cases, differences in detection and quantification limits. Determination of emissions from combustors using liquid fuels can be readily achieved using 1-hr sampling with the CDS. Emissions from gasfired combustors are very low, requiring careful attention to sample volumes. Sampling volumes corresponding with 6-hr operation were used for the combined mass and broad chemical speciation. Particular attention to dilution sampler operation with clean dilution air also is essential for gas-fired sources. PMID- 17269233 TI - Dilution-based emissions sampling from stationary sources: Part 2--Gas-fired combustors compared with other fuel-fired systems. AB - With the recent focus on fine particle matter (PM2.5), new, self-consistent data are needed to characterize emissions from combustion sources. Such data are necessary for health assessment and air quality modeling. To address this need, emissions data for gas-fired combustors are presented here, using dilution sampling as the reference. The dilution method allows for collection of emitted particles under conditions simulating cooling and dilution during entry from the stack into the air. The sampling and analysis of the collected particles in the presence of precursor gases, SO2 nitrogen oxide, volatile organic compound, and NH3 is discussed; the results include data from eight gas fired units, including a dual-fuel institutional boiler and a diesel engine powered electricity generator. These data are compared with results in the literature for heavy-duty diesel vehicles and stationary sources using coal or wood as fuels. The results show that the gas-fired combustors have very low PM2.5 mass emission rates in the range of approximately 10(-4) lb/million Btu (MMBTU) compared with the diesel backup generator with particle filter, with approximately 5 x 10(-3) lb/MMBTU. Even higher mass emission rates are found in coal-fired systems, with rates of approximately 0.07 lb/MMBTU for a bag-filter-controlled pilot unit burning eastern bituminous coal. The characterization of PM2.5 chemical composition from the gas-fired units indicates that much of the measured primary particle mass in PM2.5 samples is organic or elemental carbon and, to a much less extent, sulfate. Metal emissions are quite low compared with the diesel engines and the coal- or wood-fueled combustors. The metals found in the gas-fired combustor particles are low in concentration, similar in concentration to ambient particles. The interpretation of the particulate carbon emissions is complicated by the fact that an approximately equal amount of particulate carbon (mainly organic carbon) is found on the particle collector and a backup filter. It is likely that measurement artifacts, mostly adsorption of volatile organic compounds on quartz filters, are positively biasing "true" particulate carbon emission results. PMID- 17269234 TI - Characteristics of photocatalytic oxidation of toluene, benzene, and their mixture. AB - The investigation of the photocatalytic oxidation (PCO) of multicomponent volatile organic compounds (VOCs) is very important to the application of PCO technology, because there is seldom a single VOC component in indoor air. In this paper, the characteristics of binary indoor VOCs, toluene and benzene, were experimentally studied using a mass transfer based method that we developed. The concentration ranges for toluene and benzene were 4.48-27.4 mg/m3 and 1.82-4.08 mg/m3, respectively. We found the following: (1) the PCO of each individual contaminant studied obeys the unimolecular form of the Langmuir-Hinshelwood (L-H) rate form; (2) the PCO of the binary contaminants follow the competitive adsorption L-H rate form; (3) the reaction-coefficient for PCO of individual contaminants differs from that in the competitive adsorption L-H rate form; and (4) the component impact factor of A to B, put forward in this paper, is a useful parameter describing the influence of A on the reaction coefficient of B, and it was found that the impact factor of toluene (a chemically active component) on benzene (a chemically stable component) is high, and the impact factor of benzene on toluene is low. PMID- 17269235 TI - Energy use and emissions from marine vessels: a total fuel life cycle approach. AB - Regional and global air pollution from marine transportation is a growing concern. In discerning the sources of such pollution, researchers have become interested in tracking where along the total fuel life cycle these emissions occur. In addition, new efforts to introduce alternative fuels in marine vessels have raised questions about the energy use and environmental impacts of such fuels. To address these issues, this paper presents the Total Energy and Emissions Analysis for Marine Systems (TEAMS) model. TEAMS can be used to analyze total fuel life cycle emissions and energy use from marine vessels. TEAMS captures "well-to-hull" emissions, that is, emissions along the entire fuel pathway, including extraction, processing, distribution, and use in vessels. TEAMS conducts analyses for six fuel pathways: (1) petroleum to residual oil, (2) petroleum to conventional diesel, (3) petroleum to low-sulfur diesel, (4) natural gas to compressed natural gas, (5) natural gas to Fischer-Tropsch diesel, and (6) soybeans to biodiesel. TEAMS calculates total fuel-cycle emissions of three greenhouse gases (carbon dioxide, nitrous oxide, and methane) and five criteria pollutants (volatile organic compounds, carbon monoxide, nitrogen oxides, particulate matter with aerodynamic diameters of 10 microm or less, and sulfur oxides). TEAMS also calculates total energy consumption, fossil fuel consumption, and petroleum consumption associated with each of its six fuel cycles. TEAMS can be used to study emissions from a variety of user-defined vessels. This paper presents TEAMS and provides example modeling results for three case studies using alternative fuels: a passenger ferry, a tanker vessel, and a container ship. PMID- 17269236 TI - Theoretical study of the impact of particulate matter gravitational settling on ambient coarse particulate matter monitoring for agricultural emissions. AB - The particle size distributions (PSDs) of particulate matter (PM) in the downwind plume from simulated sources of a cotton gin were analyzed to determine the impact of PM settling on PM monitoring. The PSD of PM in a plume varies as a function of gravitational settling. Gravitational settling has a greater impact on the downwind PSD from sources with PSDs having larger mass median diameters (MMDs). The change in PSD is a function of the source PSD of emitted PM, wind speed, and downwind distance. Both MMD and geometric standard deviation (GSD) in the downwind plume decrease with an increase in downwind distance and source MMD. The larger the source MMD, the greater the change in the downwind MMD and GSD. Also, the greater the distance from the source to the sampler, the greater the change in the downwind MMD and GSD. Variations of the PSD in the downwind plume significantly impact PM10 sampling errors associated with the U.S. Environmental Protection Agency (EPA) PM10 samplers. For the emission sources with MMD > 10 microm, the PM10 oversampling rate increases with an increase in downwind distance caused by the decrease of GSD of the PSD in the downwind plume. Gravitational settling of particles does not help reduce the oversampling problems associated with the EPA PM10 sampler. Furthermore, oversampling rates decrease with an increase of the wind speed. PMID- 17269237 TI - Centration during hyperopic LASIK using the coaxial light reflex. PMID- 17269238 TI - Reproducibility of flap thickness. PMID- 17269239 TI - Visual outcome and aberration measurement in patients with aborted LASIK flaps. PMID- 17269240 TI - Visian Collamer phakic intraocular lens in high myopic Asian eyes. AB - PURPOSE: To evaluate the safety and efficacy of the Implantable Collamer Lens (Visian), a phakic intraocular lens (PIOL), in the correction of high myopia in Asian eyes. METHODS: This prospective study comprised 61 eyes in 40 Chinese patients with mean preoperative manifest spherical equivalent refraction of 14.54 +/- 3.61 diopters (D) (range: -7.00 to -24.75 D) who underwent Visian PIOL implantation from May 2002 to December 2004. The anatomical differences between Asian and Caucasian eyes were compared. RESULTS: Mean follow-up was 13.67 +/- 8.51 months (range: 1 to 32 months). Predictability of the manifest spherical equivalent refraction to within +/- 1.00 D was achieved in 88% of eyes and +/- 0.50 D in 72.5% of eyes. The mean postoperative manifest spherical equivalent refraction was -0.10 +/- 0.74 D, with 97% of eyes maintaining or gaining > or = 1 lines of best spectacle-corrected visual acuity (BSCVA). Two eyes lost 1 line of BSCVA. Retinal detachment developed in 1 eye 15 months after initial surgery. Because of the statistical differences in anterior chamber depth and white-to white distance between Caucasian and Chinese eyes, the Visian PIOL size was more accurate if the calculation was modified so that 0.5 mm was added to the white-to white measurement if the anterior chamber depth was < or = 3.0 mm and 1.0 mm to the white-to-white measurement if the anterior chamber depth was >3.0 mm. Initial incorrect sizing using the original nomogram led to the only cataract in our series. CONCLUSIONS: The implantation of the Visian PIOL for correcting moderate to high myopia in Asian eyes shows similar safety and efficacy to the FDA clinical trial of Caucasian eyes. Proper sizing of the Visian PIOL is important and differs slightly in Asian eyes. PMID- 17269241 TI - Wavefront-guided LASIK for myopia using the LADAR CustomCornea and the VISX CustomVue. AB - PURPOSE: To evaluate the objective and subjective visual outcomes and refractive results of wavefront-guided LASIK with LADAR CustomCornea and VISX CustomVue. METHODS: This prospective randomized single-institution multisurgeon study comprised 100 eyes of 58 patients (50 eyes on each laser platform). Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), and manifest refraction were measured postoperatively at 1 day, 1 week, 1 month, and 3 months. Contrast sensitivity, higher order aberrations measurement, and a subjective vision questionnaire were performed preoperatively and at 3 months. RESULTS: Preoperatively, the CustomCornea group had a mean manifest sphere of 3.58 +/- 1.61 diopters (D) (range: -0.50 to -7.25 D), cylinder of +0.64 +/- 0.45 D (range: 0 to +1.75 D), and manifest refractive spherical equivalent (MRSE) of 3.26 +/- 1.56 D. The CustomVue group had a manifest sphere of -4.00 +/- 1.69 D (range: -1.50 to -7.50 D), cylinder of +0.60 +/- 0.52 D (range: 0 to +2.00 D), and MRSE of -3.70 +/- 1.64 D. At 3 months, 94% of CustomCornea eyes and 84% of CustomVue eyes had UCVA > or = 20/20 (P = .20). Twenty-four percent of CustomVue eyes and 22% of CustomCornea eyes gained 1 line of BSCVA. In both groups, 96% of eyes were within 0.50 D of emmetropia. Mean CustomCornea glare contrast sensitivity improved (P = .04) whereas more eyes improved than worsened in both groups. Spherical aberration and total higher order aberrations increased, and trefoil decreased in both groups. A decrease in coma was noted in 70% of CustomCornea eyes. CONCLUSIONS: Wavefront-guided LASIK with both platforms is safe, effective, and delivers excellent visual results. CustomCornea improves contrast sensitivity under glare conditions. PMID- 17269242 TI - Optical analysis of presbyLASIK treatment by a light propagation algorithm. AB - PURPOSE: To evaluate the changes in the optical quality of corneas of hyperopic patients operated using central multifocal presbyLASIK treatment through the study of light patterns around the retinal plane. METHODS: This study included eight hyperopic eyes that underwent central presbyLASIK surgery with Presby-one software using an H. Eye Tech Technovision excimer laser platform. Mean patient age was 57 years. Mean preoperative spherical equivalent refraction was 1.28 +/- 0.87 diopters (D). Mean distance decimal visual acuity with correction was 1.02 +/- 0.13 and without correction was 0.37 +/- 0.15. The optical quality was characterized by the Strehl ratio, the spot size on the retina, and objective decimal visual acuity calculated based on measured corneal topography using Fresnel propagation algorithm based on a realistic eye model. RESULTS: The postoperative spherical equivalent refraction was -0.55 +/- 0.48 D. The distance decimal visual acuity with correction was 0.94 and without correction was 0.70. The pseudoaccommodation range was 1.60 +/- 0.40 D. A good Pearson correlation coefficient was obtained (r2 = 0.86) for the linear fit between the real and calculated decimal visual acuity for the eight eyes. The Strehl ratio value on the retinal plane increased after the surgery by a mean factor of 4.7. CONCLUSIONS: With a complete characterization of the eye and a complete propagation algorithm (that takes into account all refractive surfaces in the eye at the same time), it is possible to evaluate the optical quality in eyes of patients who have undergone central presbyLASlK treatment. PMID- 17269243 TI - LASIK flap characteristics using the Moria M2 microkeratome with the 90-microm single use head. AB - PURPOSE: To evaluate the accuracy and consistency of corneal flap thickness, horizontal diameter, and hinge size with the Moria M2 90-microm single use head. METHODS: Fifty-two myopic patients (104 eyes), mean age 32.6 years, underwent bilateral LASIK with a superior hinged flap using the Moria M2 microkeratome (90 microm single use head). Prospective evaluation included flap thickness (subtraction method), diameter, hinge size, interface particles, intraoperative complications, and visual recovery. RESULTS: The mean preoperative spherical equivalent refraction was -5.72 +/- 2.59 diopters (D) (range: -2.88 to -10.75 D) and -5.84 +/- 2.73 D (range: -3.13 to -9.38 D) for right and left eyes, respectively. The mean preoperative central corneal thickness was 548 +/- 24 microm and 547 +/- 25 microm for right and left eyes, respectively. The mean preoperative steepest K was 44.12 +/- 1.28 D and 44.41 +/- 1.27 D for right and left eyes, respectively. Corneal diameter (white-to-white) was 12 +/- 0.4 mm and 11.9 +/- 0.4 mm for right and left eyes, respectively. The mean postoperative flap thickness was 109 +/- 18 microm (range: 67 to 152 microm) and 103 +/- 15 microm (range: 65 to 151 microm) for right and left eyes, respectively. The mean postoperative flap diameter was 9.4 +/- 0.3 mm (expected mean according to the nomogram given by the company was 9.5 mm). The mean postoperative hinge chord was 4.4 +/- 0.4 mm (expected mean 4.2 mm). No interface particles were detected on slit-lamp examination. CONCLUSIONS: The Moria M2 90-microm single use head is safe with reasonable predictability for LASIK flap creation. PMID- 17269244 TI - Phototherapeutic keratectomy for epithelial irregular astigmatism: an emphasis on map-dot-fingerprint degeneration. AB - PURPOSE: To study the changes in irregular astigmatism in patients with recurrent corneal erosion syndrome due to map-dot-fingerprint degeneration and to demonstrate that both symptomatic and asymptomatic map-dot-fingerprint degeneration/recurrent corneal erosion syndrome may be related to irregular astigmatism, which can effectively be corrected by phototherapeutic keratectomy (PTK) or standard spherical photorefractive keratectomy (PRK). METHODS: Eleven eyes with irregular astigmatism related to map-dot-fingerprint degeneration/recurrent corneal erosion syndrome with and without changes at the slit-lamp microscope were treated with PTK or spherical PRK, which was performed with a VISX S2 or S4 excimer laser. All eyes underwent videokeratography performed pre- and postoperatively using either the Tomey TMS-2N Topographic Modeling System or EyeSys Technologies Corneal Analysis System 2000. RESULTS: Mean pre- and postoperative best spectacle-corrected visual acuity (BSCVA) was 0.18 +/- 0.14 logMAR and 0.04 +/- 0.04 logMAR, respectively. This improvement in BSCVA was statistically significant. The mean gain in Snellen lines was 2.4 +/- 2.1. Preoperative corneal videokeratography showed irregular astigmatism with an elevation pattern that was corrected in all eyes despite the fact that no astigmatic photorefractive correction was performed. CONCLUSIONS: Following PTK, eyes with irregular astigmatism related to map-dot-fingerprint degeneration showed significant improvement in BSCVA and correction of irregular astigmatism as revealed by videokeratography. This study shows that irregular astigmatism can be exclusively of epithelial origin and in some eyes abnormal corneal epithelium may create optical aberrations. This possibility should be taken into account when, for example, wavefront-guided stromal photoablation procedures are being planned. PMID- 17269245 TI - Femtosecond laser keratome creation of partial thickness donor corneal buttons for lamellar keratoplasty. AB - PURPOSE: To evaluate the thickness and diameter accuracy of the IntraLase femtosecond laser in harvesting corneal discs for lamellar keratoplasty. The stromal bed quality of resected corneas was evaluated by scanning electron microscopy. METHODS: Two IntraLase units were used to create corneal discs at 225 , 300-, 400-, and 500-microm thickness settings and 7-, 8-, 8.5-, and 9-mm diameter settings (n = 28). Achieved thickness was measured using a digital caliper and achieved diameter was measured using imaging software. Samples were preserved and processed for scanning electron microscopy to observe stromal bed quality. RESULTS: On both units, the mean deviation from attempted thickness was 9.5 +/- 8.6 microm (range: +6 to -28 microm). All of the obtained corneal discs were circular (horizontal versus vertical diameters, P > .05). The raster pattern produced a smoother stromal bed compared to the spiral pattern. CONCLUSIONS: The IntraLase femtosecond laser keratome provides depth and diameter accuracy even at increased depth settings. Stromal bed was smooth with the raster pattern and can further be smoothed by excimer phototherapeutic keratectomy treatment. Femtosecond laser lamellar keratoplasty is a promising procedure and clinical data are needed to determine effectiveness. PMID- 17269247 TI - Corneal hysteresis, resistance factor, topography, and pachymetry after corneal lamellar flap. AB - PURPOSE: To measure prospectively the early changes in corneal hysteresis, topography, and pachymetry after the creation of a stromal flap cut without laser photoablation. METHODS: A 37-year-old man was referred for a bioptic procedure to correct for compound myopic astigmatism in the left eye. A 159-microm-thick 8x8.5 mm superior hinged flap was created with a mechanical microkeratome in the left cornea. Changes in the corneal hysteresis, corneal resistance factor, Goldmann correlated intraocular pressure (lOP), corneal compensated IOP, anterior and posterior topography, and optical and ultrasound pachymetry were monitored prospectively before and at 1 hour, 1 day, 5 days, and 25 days after flap creation. The right eye served as a control. RESULTS: In the left eye, corneal hysteresis and corneal resistance factor decreased immediately after the flap cut and remained lower than preoperatively at 1 hour, 1 day, 5 days, and 25 days. Corneal compensated IOP varied significantly less than Goldmann correlated IOP in both eyes. Central flattening of the horizontal meridians was observed on the difference topography maps. The values of the left eye posterior best fit sphere increased after the flap cut. Increased central corneal thickness occurred immediately after the flap cut and decreased over time without returning to its preoperative value. CONCLUSIONS: The creation of a stromal flap can modify the biomechanical properties of the cornea, including a reduction in corneal hysteresis. The topographic changes were consistent with previously reported cases of flap cut in normal corneas. PMID- 17269246 TI - Surface wave elastometry of the cornea in porcine and human donor eyes. AB - PURPOSE: To introduce a nondestructive technique for characterization of corneal stiffness, determine measurement precision, and investigate comparative stiffness values along central, radial, and circumferential vectors in porcine corneas. The effects of epithelial debridement, relaxing incisions, and crosslink-mediated stiffening on surface wave velocity are also studied. METHODS: A handheld prototype system was used to measure ultrasound surface wave propagation time between two fixed-distance transducers along a ten-position map. Repeatability was assessed with replicate measurements in 6 porcine corneas. In 12 porcine globes with controlled intraocular pressure (IOP), serial measurements were performed before and after epithelial removal, then after 250- and 750-microm deep relaxing incisions. In human globes with constant intravitreal pressure, central wave velocity and transcorneal IOP measurements were compared before and after collagen cross-linking. RESULTS: Measurement repeatability across all regions was between 2.2% and 8.1%. Epithelial removal resulted in increases in measured stiffness in 67% of eyes, but statistical power was insufficient to detect a systematic change. Wave velocity across a central incision decreased significantly after 250-microm keratotomy (P < .001), but did not undergo a significant further decrease with deeper keratotomy. Meridional stiffness changes consistent with coupling effects were detected after keratotomy. Surface wave velocity and transcorneal IOP measurements increased markedly after collagen cross-linking despite maintenance of a constant IOP. CONCLUSIONS: Handheld corneal elastometry provides a repeatable measure of regional stiffness changes after relaxing incisions and collagen cross-linking in in vitro experiments. Surface wave elastometry allows focal assessment of corneal biomechanical properties that are relevant in refractive surgery, ectatic disease, and glaucoma. PMID- 17269248 TI - How might corneal elasticity help us understand diabetes and intraocular pressure? AB - PURPOSE: To determine how changes in corneal elasticity/stiffness might influence intraocular pressure (IOP) readings in diabetic patients. METHODS: A systematic review of the literature was performed to understand the conflicting relationship between diabetes, elevated IOP, and glaucoma progression. RESULTS: Diabetic patients have been found to have statistically significant higher IOP readings in some population-based studies compared to non-diabetics. Insulin resistance states, hyperglycemia and glycosylated hemoglobin have been correlated with higher IOP (1 mmHg) measurements in diabetic patients. In the Ocular Hypertension Treatment Study (OHTS), a self reported history of diabetes was found to be protective against the progression of primary open-angle glaucoma. Small differences in IOP measurements in diabetic patients may be due to corneal stiffening, as demonstrated by the protective effect of glucose-mediated collagen cross-linking against the manifestation and keratometric progression of keratoconus. Different collagen cross-linking agents may induce different degrees of corneal stiffening, which can result in differences in measured IOP. CONCLUSIONS: Glucose-mediated corneal stiffening due to collagen cross-linking might be responsible for IOP overestimation in diabetic patients. Corneal stiffening might explain why diabetic eyes tend to have higher IOP readings in large population-based studies and why those with ocular hypertension have a reduced risk for glaucoma progression. PMID- 17269249 TI - Sectorial and annular quantitative area pachymetry with the Orbscan II. AB - PURPOSE: To present a new application of quantitative area pachymetry of the cornea. METHODS: Sectorial quantitative area pachymetry of small corneal zones located at the center and surrounding areas is possible by means of the statistical analysis device and tools menu of Orbscan II (Bausch and Lomb). RESULTS: Average pachymetry of 1 central zone and 12 small zones around the center may be shown in the pachymetry map by simply formatting the system. Average pachymetry, standard deviation, rate of thickness variation (slope), and volume of analyzed annular corneal zone can also be automatically shown in a data window. The examination results can be printed and kept on record. CONCLUSIONS: The method is simple and descriptive. This type of preoperative evaluation may guide the manual or laser preparation of channels for intracorneal segments and the corneal trephination for lamellar or penetrating keratoplasty. PMID- 17269250 TI - Reduced best spectacle-corrected visual acuity from inserting a thicker Intacs above and thinner Intacs below in keratoconus. AB - PURPOSE: To report a case of decreased best spectacle-corrected visual acuity (BSCVA) 2 months after Intacs implantation. METHODS: A 33-year-old woman with keratoconus and contact lens intolerance underwent Intacs surgery in the left eye at another institution. Two segments were used--a thinner one (0.25 mm) below the cone and a thicker one (0.35 mm) above the cone. RESULTS: Two months postoperatively, the patient presented to our practice with BSCVA reduced from 20/20 to 20/30. The superior Intacs segment was explanted, the inferior segment was exchanged for a thicker one (0.35 mm), and collagen cross-linking with riboflavin treatment was performed. This resulted in visual, topographic, and refractive improvement with BSCVA returning to 20/20. CONCLUSIONS: Single inferior segment Intacs may be more appropriate for paracentral and peripheral cones. Collagen cross-linking may help cause further flattening. Using asymmetrical segments, with the thicker segment above the cone, may increase distortions and result in loss of BSCVA. PMID- 17269251 TI - Corneal haze following PRK with mitomycin C as a retreatment versus prophylactic use in the contralateral eye. AB - PURPOSE: To report photorefractive keratectomy (PRK) treated with mitomycin C (MMC) for previous corneal haze in one eye and PRK with MMC to prevent corneal haze formation in the fellow eye. METHODS: A 40-year-old woman underwent PRK with MMC to treat previous corneal haze (secondary to previous PRK without MMC) for residual refractive error of +0.50 +0.25 x 165 in the left eye and PRK with MMC to prevent corneal haze in the right eye. RESULTS: Postoperative slit-lamp examination revealed no haze in the right eye, but continued mild haze in the left eye. CONCLUSIONS: Treatment with PRK and MMC for previous corneal haze is not as effective as primary PRK with MMC in preventing postoperative corneal haze formation. PMID- 17269252 TI - Corneal ectasia after hyperopic LASIK. AB - PURPOSE: To report two cases of corneal ectasia, which developed after hyperopic LASIK. METHODS: Preoperative pellucid marginal corneal degeneration was observed in patient 1. Patient 2 had no preoperative risk factors. RESULTS: Patient 1, a 47-year-old man, developed corneal ectasia in his right eye 6 months after unilateral hyperopic LASIK. Preoperative manifest refraction was +2.00 +1.50 x 178 in the right eye and +1.00 sphere in the left eye. Corneal thickness was 585 microm and 575 microm (right and left eye, respectively). Preoperative topography of the right eye demonstrated inferior steepening in the far periphery, suggestive of early pellucid marginal corneal degeneration. Patient 2, a 35-year old man, developed corneal ectasia in his right eye > 3 years after bilateral LASIK. Preoperative manifest refraction was +2.50 sphere and +3.25 sphere (right and left eye, respectively), and corneal thickness was 556 microm in both eyes. Preoperative topography was normal in both eyes with no evidence of asymmetry, steepening, or irregularity. CONCLUSIONS: Corneal ectasia can occur after hyperopic LASIK in patients with or without recognized preoperative risk factors. Although uncommon, patients with pellucid marginal corneal degeneration can have hyperopic refractions and are at high risk for developing corneal ectasia after LASIK. PMID- 17269253 TI - Removal of an intracorneal hydrogel implant for hyperopia after LASIK. AB - PURPOSE: To report a case of intracorneal hydrogel lens implantation for hyperopia after repeat LASIK surgery. METHODS: A 34-year-old man underwent intracorneal lens implantation following two LASIK procedures for correction of hyperopia. RESULTS: The decentered intracorneal lens was removed due to ocular pain and inflammation, epithelial ingrowth under the corneal flap, and high order aberrations. Pain and inflammation resolved, and corneal stability was regained > 6 months after removal of the lens. CONCLUSIONS: Intracorneal lenses may require explantation if previous laser ablative procedures fail to correct refractive errors. PMID- 17269254 TI - [Changes in oral mucosa of the partially edentulous who wear removable partial dentures ]. AB - PURPOSE: to confirm or infirm structural modification of oral mycosis at the summit after fifteen days of wearing removable resin partial dentures. METHODS: our study took place at the health center of Rufisque in Senegal from January to July 1998, involved fourteen patients divided into two groups according to sex: seven males and seven females who came for removable resin partial dentures. The macroscopic examination was conducted through to inspection and touching of mycosis at the level of toothless summit before the wearing of the denture. A biopsy was conducted on each patient before and after the wearing of the resin dentures. Tissue reaction was appreciated qualitatively through morphological analysis. RESULTS: Before the wearing of the removable resin partial dentures 92.9% of patients had epithelial hyperplasia; 7.1% epithelial hypoplasia and 85.7% keratosis at the level of the chorion the number of collagen fibbers (28.6% discrete, 50% moderate, 21.4% important), fibroblasts (35.7% discrete; 42.9% moderate ; 21.4% important), inflammatory cells (71.4% discrete; 28.6% moderate; 0% important) and for blood vessels (64% discrete; 35.70% moderate; 0% important) after fifteen days of wearing partial denture. After fifteen days of the wearing removable resin partial dentures: 85.7% of patients had epithelial hyperplasia; 14.3% normal epithelial and 100% de keratosis at the level of the chorion the number of collagen fibbers (14.3% discrete; 21.4% moderate; 64.3% important), fibroblasts (42.9% discrete; 42.90% moderate; 14.3% important), inflammatory cells (50% discrete, 35.7% moderate: 14.3% important), blood vessels (43% discrete; 28.6% moderate; 28.6% important). CONCLUSION: Biopsies of the summit are reliable contribution; they provide precise information on the quality of tissue supporting resin partial dentures. This tissues may seem healthy appearance (inspection and touching) but show sign of suffering at this anatomy pathological examination. PMID- 17269255 TI - [Evaluation of gingival condition in homozygous children and adolescents with sickle cell anemia in Senegal]. AB - Sickle cell anaemia is an inherited disorder of haemoglobin synthesis leading to haemolytic anaemia. It touches more than 50 million people in the world and 10% of the population in Senegal. Only the homozygous form is symptomatic and appears by painful crises of vaso-occlusive type. There is a lack of works carried out or published in Senegal about potential link between periodontal conditions and sickle-cell anaemia. The main objective of this study is to assess the gingival conditions in Senegalese children and adolescents homozygous sickle cell anaemic. Secondary, the gingival state is correlated with oral hygiene and rate of reticulocytes to determine their relationship. Fifty homozygous attending the Albert Royer Paediatric Hospital of Dakar and unscathed of other systemic pathologies, were examined. The patients are old between 3 and 16 years with an average age 9.4 years +/- 3.8. The gingival state is assessed by measurement of the gingival index (GI) and index of sulculary bleeding (SBI). Partial correlation is performed between the two indexes and average of reticulocytes. The gingival index mean is 1.7 +/- 0.6 and 66% of the patients present a severe inflammation, which is more frequent in the age bracket from 3 to 12 years. The SBI mean is 1 +/- 1.1 and 68% of the patients present gingival bleeding, which is moderate to severe in 18%, with a greater frequency in the age bracket from 13 to 16 years. Strong correlation is found between plaque index, GI and SBI. Damage of gingival state seems not to be linked to the high average of reticulocytes controlling for oral hygiene. Children and adolescent homozygous have an inflammatory periodontium associated to poor oral hygiene, which highlights their needs in periodontal treatments. Early tracking and preventive treatment of periodontal diseases during systematic oral visits must be required. PMID- 17269256 TI - Pattern and distribution of cervical dentine hypersensitivity in a Nigerian tertiary hospital. AB - The purpose of the study was to investigate the prevalence of Cervical Dentine Hypersensitivity in a Nigerian Tertiary Hospital and to highlight its pattern of distribution intraorally. Two hundred and twenty subjects, aged 18 to 60 years, attending the Restorative Clinic of the hospital were assessed for dentine hypersensitivity gingival recession and oral hygiene status over a 3 month period. Whereas the sensitivity occurred in 16.3% of the study population, it was seen most frequently in the 31 to 40 year age range (48.5%). Furthermore, the incidence was higher in women (66.7%) than in men (33.3%). Also, it occurred most often in subjects with good oral hygiene (63.6%) and in right handed (81.8%) subjects. It was commonest on the buccal surfaces of teeth (60.6%) canines (39.4%) and mandibular arch (63.6%). Within the limitations of the current study, cervical dentine hypersensitivity was fairly common and it also occurs mostly on the buccal surfaces of teeth, canines and in the mandibular arch. PMID- 17269257 TI - [Surgical and Orthodontic Treatment of Impacted Canines: A Clinical Report]. AB - Impaction of tooth can be defined as a failure of a tooth to emerge usually due to insufficient space or the presence of a supernumerary tooth blocking its path of eruption. Impaction of the canines deserves particular attention due to their importance regarding occlusal stability and aesthetic. A case of a young girl who presented with an impaction of both upper canines and the lower left canine is reported here. Good therapeutic results have been obtained after 18 month of treatment with a multidisciplinary team involving oral surgeons, periodontists and orthodontists. PMID- 17269258 TI - [Performance and Compatibility of Self Polymerizing Prime and Bond NT Adhesive and the Composite LuxaCore]. AB - AIM: To evaluate the performance of bond strength and the compatibility of Prime &Bond NT self etching adhesive resins without activator on dentin surface with dual composite resin LuxaCore, and verify the contribution of a coactivator. MATERIAL AND METHODS: twenty-four human teeth without decay, molars or pre-molar are used. The dental crowning is cut with diamond disc mounted on a hand piece; the roof surface is flattened and well humidified. Each tooth is embedded in cold self-etching resin (Plexil Excil). Samples are divided into two groups of 12. in the first group, self-etching Prime &Bond NT resin adhesive without activator is supplied on the flat mesial dentin roots, then dual cure composite resin LuxaCore) is bonded. The second group was subject to the same treatment but with addition of co-activator the Prime &Bond NT self-etching adhesive resin. Debonding was achieved with Universal testing machine and mean shear bond strengths were determined for each test group. The data were subjected to ANOVA (p < 0001). RESULT: Bond strength obtained with self-etching Prime &Bond NT without activator is 10.635 MPa. With addition of activator it is 15.185 MPa CONCLUSION: supplementing with an activator has significantly improved bonding strength. PMID- 17269259 TI - Occupational exposures and infection control among students in Nigerian dental schools. AB - OBJECTIVE: To assess the incidence of occupational exposures to body fluids and infection control practices among students in Nigerian dental schools. MATERIALS AND METHODS: A self-administered questionnaire survey of 112 students from three Nigerian dental schools. RESULTS: 57 (50.9%) of the students had experienced one or more occupational exposures in the previous six months. There was no statistically significant association between year group and reported number of exposures (p > 0,05). There was also no statistically significant association between sex and reported number of exposures (p > 0.05). 50.7% of the exposures were percutaneous injuries, 26.1% splatter of saliva and 23.2% splatter of aerosol. Percutaneous injuries were most frequently caused by scalers (42.9%) and needlesticks (37.1%) Most incidents occurred during scaling (37.7%),use of dental handpiece (21.7%) and cleaning of instruments (18.8%). 96.4% of the exposures were not reported. Only 36.6% of the students were immunized against Hepatitis B. None of those immunized had been post-screened for seroconversion. The routine use of gloves, masks and protective eyewear was reported by 87.5%, 65.5% and 17% of students respectively. CONCLUSIONS: This study indicates a high rate of exposure to body fluids and low compliance with infection control guidelines. There is a need for interventions to improve safe work practices, hepatitis B vaccination, HBV post-immunization serology and use of protective barriers. Also appropriate policies and procedures are needed for reporting and managing exposures. PMID- 17269260 TI - A new prescription for health care? PMID- 17269261 TI - Unhealthy lifestyle in college students could lead to diabetes risk. PMID- 17269262 TI - Improving revenue collections: a primer. Part 3: follow-up with payers. PMID- 17269264 TI - Your pension or IRA: still a 70%+ tax trap after all these years. PMID- 17269263 TI - Should we limit the ferritin upper threshold to 500 ng/ml in CKD patients? AB - The new National Kidney Foundation's Kidney Disease Outcome Quality Initiative clinical practice guidelines for anemia management in chronic kidney disease include several important modifications to the previous recommendations. These changes may have major implications in clinical practice and outcome of the chronic kidney disease patient population. Among the important guideline modifications are the elimination of the upper thresholds for hemoglobin (12 g/dL), transferrin saturation ratio (TSAT, v 50%) and ferritin (800 ng/ml). There are, however, additional recommendations pertaining to anemia management when hemoglobin is above 13 g/dL or serum ferritin above 500 ng/ml. The KDOQI anemia working group explains that the upper ferritin level of 500 ng/ml is not a stopping point for IV iron administration, but adds that decisions regarding IV iron administration should weigh erythropoietin responsiveness, hemoglobin and transferrin saturation level, and the patient's clinical status.The selected upper ferritin level of 500 ng/ml lacks adequate scientific evidence in the CKD population. Approximately half of all maintenance hemodialysis patients in the United States may have a serum ferritin above 500 ng/ml. Serum ferritin in 500 1,200 ng/ml range is not associated with increased death risk in hemodialysis patients if controlled for the confounding effect of malnutrition and inflammation. Given the lack of support from the literature, any attempt to contemplate an upper limit for serum ferritin would be arbitrary, and would not serve to improve the quality of treatment in the CKD population. PMID- 17269265 TI - Who is not ready? PMID- 17269266 TI - The concept of "being in recovery". PMID- 17269267 TI - Putative evidence of employment readiness. AB - Readiness in the work domain has been a controversial issue for the psychiatric rehabilitation community. Judgments of a lack of readiness have relegated many persons to lives of continued unemployment and service dependency. Conversely, proponents of the rapid placement strategy of supported employment have down played the importance of readiness. Yet, a careful review of the supported employment research suggests that readiness may indeed be an important factor in vocational outcomes. This paper presents evidence that the screening criteria employed in SE studies are often related to readiness factors and that these criteria are highly predictive of vocational outcomes. Acceptance of the importance of readiness for success in the vocational arena implies new service strategies and may serve to improve vocational outcomes in general. PMID- 17269268 TI - Assessing the underutilization of supported employment services. AB - Supported Employment Services (SES) are evidence-based practices that appear to be underutilized. This study evaluated the level of SES underutilization at both urban and suburban agencies that served people with psychiatric disabilities. Two hundred sixty-nine unemployed consumers indicated their intentions to accept a referral to SES in the next 6 months. The 54 practitioners who served these consumers indicated their intentions to refer these consumers to SES during that time period. The concordance rate between the consumers' and practitioners' intentions was 55%. Urban and suburban agencies did not differ in concordance rate. Forty-nine percent of the consumers intended to accept a referral but their practitioners intended to refer 21%. An underutilization rate of 28% was found for the combined agencies. The factors contributing to the consumers' and practitioners' intentions were also investigated. The low concordance rate between these consumers and practitioners may have been due to their different perspectives about the importance of the consumers' felt need to work. PMID- 17269269 TI - Evaluation of a combined supported computer education and employment training program for persons with psychiatric disabilities. AB - Meaningful work is described as one of the functional indicators of healing and growth beyond the disability and is seen as critical in recovering a personal sense of worth and value. We describe a supported education-supported employment program which focused on teaching computer, recovery and work skills. A program evaluation was implemented on four consecutive classes of this program. Four classes with a convenience sample of sixty-one students were involved in the evaluation over years. The program utilized a one group pretest, posttest design, with repeated measures over time. Following the 10-month classroom training phase, students entered a 2-month internship to give them computer office work experience. Students were interviewed quarterly using standardized assessments involving work and other subjective outcomes. Results suggest that overall the students experienced a positive change in work status and income and a decrease in mental health services utilization. In addition, non-vocational outcomes, specifically self-esteem and empowerment improved. The program represents a successful integration of supported education and supported employment program models. PMID- 17269270 TI - Integration of cognitive behavioral therapy into psychiatric rehabilitation day programming. AB - Cognitive Behavioral Therapy has substantial empirical support for the treatment of people with severe and persistent mental illnesses. Efforts to integrate this type of therapy into psychiatric rehabilitation practices are growing. This paper describes an innovative integration of Cognitive Behavioral Therapy into a psychiatric rehabilitation day program attended by people with severe and persistent mental illnesses and frequently co-occurring substance use disorders. The challenges of maintaining the cognitive model and other core features of Cognitive Behavioral Therapy in a heterogeneous, large, group-based program are discussed. PMID- 17269271 TI - Peer support for persons with co-occurring disorders and community tenure: a survival analysis. AB - Individuals with co-occurring mental health and substance abuse diagnoses experience high rehospitalization rates. Consumer-delivered services are recognized as an important intervention for this population, but no studies have examined the extent to which such services are associated with enhanced community tenure and prevention of rehospitalizations. This longitudinal, comparison group study examines the effect of participation in The Friends Connection, a peer support program for individuals with co-occurring disorders, on 3-year rehospitalization patterns. Results from a survival analysis suggest that program participants have longer community tenure (i.e., periods of living in the community without rehospitalization) than a comparison group. Chi-square tests also indicate that significantly more people in the comparison group (73%) are rehospitalized in a 3-year period versus those in the Friends Connection group (62%). These results suggest that Friends Connection may facilitate community tenure and prevent rehospitalizations for a group that is at high-risk for rehospitalizations. The findings lend additional support of the potential effectiveness of peer support programs as part of a service delivery system that facilitates recovery of individuals with co-occurring disorders. PMID- 17269272 TI - Outcomes in community-based residential treatment and rehabilitation for individuals with psychiatric disabilities: a retrospective study. AB - This study evaluated outcomes for participants of a community-based residential treatment and rehabilitation program. The study used repeated measures to retrospectively evaluate 25 individuals with severe psychiatric disabilities who completed a 1-year follow-up period after discharge from the program. Results indicated that following the program these individuals lived for significantly longer periods in the community in more independent settings and functioned at higher levels than in the 6 years prior to participation in the program. These positive outcomes suggest that residential treatment and rehabilitation may be an important consideration in the care of some individuals with severe psychiatric disabilities. PMID- 17269273 TI - Quality of life for persons living with schizophrenia: more than just symptoms. AB - Quality of life is an important outcome for persons living with schizophrenia and for the treatment of schizophrenia. However, studies of quality of life among persons living with schizophrenia have focused primarily on the symptoms experienced by the individual. This study sought to determine the influence of unmet need and social support on the quality of life of individuals with schizophrenia. Thirty-two persons living in the community with schizophrenia or schizoaffective disorder were assessed on quality of life, psychopathology, unmet need and social support. Hierarchical regression analyses indicated that unmet need and social support are important contributors to the quality of life of a person with schizophrenia, even after controlling for symptoms. Implications for schizophrenia treatment are discussed. PMID- 17269274 TI - Promoting consumer empowerment through entrepreneurship: a proposal. AB - In order to promote life control, this proposal suggests strategies to help people who use community mental health services to access small loans or "microcredit" for entrepreneurship in self-help groups. PMID- 17269275 TI - The importance of rehabilitation. PMID- 17269277 TI - The most common pediatric rashes. PMID- 17269278 TI - A 5-week-old boy with failure to thrive. PMID- 17269279 TI - A 2-month-old girl with feeding problems. PMID- 17269280 TI - Childhood viral exanthems. AB - Many viral infections exhibit cutaneous lesions. Recognition of the exanthems associated with these infections and the broader clinical scenarios in which they occur can lead to more rapid diagnosis and appropriate treatment for affected patients. PMID- 17269281 TI - Fever and rash in a child: when to worry? AB - The differential diagnosis of a fever and rash presenting in a pediatric patient is quite extensive. This article is not all-inclusive but is meant to aid in the diagnosis to differentiate serious, life-threatening eruptions from more benign common rashes. PMID- 17269282 TI - Nevi in children: a practical approach to evaluation. AB - Education is the cornerstone of melanoma prevention. Well-child examinations are an excellent opportunity to educate patients and parents about melanoma risk factors and prevention. The only modifiable risk factor for the development of melanoma and acquisition of nevi is level of sun exposure. Every patient who is evaluated for a melanocytic lesion should be educated about sun avoidance during midday, protective clothing including long-sleeved shirts, long pants, and hats with brims, and playing in shaded areas when outdoors. Proper application and appropriate uses of sunscreen should also be reviewed. PMID- 17269283 TI - Diagnosis and management of superficial cutaneous fungal infections in children. PMID- 17269284 TI - Avoiding formaldehyde allergic reactions in children. PMID- 17269285 TI - Toothpaste tech: what's the latest news in toothpaste? PMID- 17269286 TI - Prions: transmissible spongiform encephalopathies and dental transmission risk assessment. PMID- 17269287 TI - Putting the practice into evidence-based dentistry. AB - Whenever a new field emerges in health care, a period is experienced in which the field tries to define itself. This is the position evidence-based dental practice finds itself in at the moment. In this paper, it is argued that, for dentistry to enter into the brave new world of evidence-based practice, it will require some rethinking of the research enterprise in the profession. PMID- 17269288 TI - Management of the hypertensive dental patient. AB - Hypertension is a common malady and a harbinger of such diseases as heart attack and stroke. Because millions of Americans are not aware they are hypertensive or it is not adequately controlled, dentists can contribute significantly to national health by screening their patients. Dentists must also be cognizant of the implications high blood pressure has for dental practice. Specific treatment recommendations include limiting dental care in patients with severe hypertension, reducing stress, and periodically monitoring blood pressure. PMID- 17269289 TI - Calculating the maximum recommended dose of local anesthetic. AB - Since patients have a wide variance in body size, it is appropriate to base the maximum recommended dose of a local anesthetic on a milligram of drug per kilogram of body weight. Other variables (severe overweight or underweight and cardiovascular compromise) also influence the appropriate maximum recommended dose. By calculating the specific dose limit from the maximum recommended dose for each patient, the chances of a local anesthetic overdose can be significantly reduced. PMID- 17269290 TI - Laws of distraction. PMID- 17269291 TI - [Message from the Minister of Health and Societies of professional nurses]. PMID- 17269292 TI - [Travel phlebitis]. PMID- 17269293 TI - [Big plans for the nurses of Quebec]. PMID- 17269294 TI - [The point of therapy]. PMID- 17269295 TI - [Treatment and adverse effects]. PMID- 17269296 TI - [HIV and neurologic manifestations]. PMID- 17269297 TI - [Opportunistic infections]. PMID- 17269298 TI - [An effective means of prevention: efficiency of women's health]. PMID- 17269299 TI - [Arterial hypertension]. PMID- 17269300 TI - [Percutaneous implantable systems]. PMID- 17269301 TI - [Touch and the aged]. PMID- 17269302 TI - [New equipment and new technologies in the treatment of major burns]. PMID- 17269303 TI - [Introduction to blood transfusion]. PMID- 17269304 TI - [The art of nursing and importance of touch]. PMID- 17269305 TI - [Night of recruitment of nurses for the IGR]. PMID- 17269306 TI - [Kaletra, a new anti HIV agent]. PMID- 17269307 TI - [Therapeutic application of ionizing radiation]. PMID- 17269308 TI - [After 20 years in the care of patients and their families]. PMID- 17269309 TI - Encouraging developments concerning avian influenza. PMID- 17269310 TI - Health disparities and prevention: racial/ethnic barriers to flu vaccinations. AB - To address the widening disparity between Whites and non-Whites for influenza vaccination rates, this study employed the Health Belief Model to examine these rates in five racial ethnic groups (White, Latino, African American, Filipino American, and Japanese American) to identify modifiable determinants of vaccination by race/ethnicity. A 2004 telephone survey of parishioners of faith based congregations aged 50-75 years in Los Angeles and Honolulu assessed influenza vaccination rate, perceived susceptibility to influenza, perceived severity of illness, and the self-reported main barrier to influenza vaccination. Logistic regression models for each race/ethnic group predicting vaccination dependent upon perceived susceptibility to influenza, perceived severity of illness, and sociodemographic characteristics were estimated. Model parameters were used to generate standardized predictions of vaccination rates by race/ethnic group. In the multivariate models, Whites and African Americans who were very concerned about getting the flu were significantly more likely to be vaccinated (96% and 91%, respectively), compared with those who were not concerned (45% and 33%). However, vaccination rates among Latinos who were very concerned about getting the flu (54%), although significantly higher than Latinos who were not concerned (34%), were lower than for Whites and African Americans. Examination of the main barriers to vaccination revealed that Latinos were more likely to report access and cost barriers, while African Americans were more likely to raise issues of mistrust such as concern that the vaccine causes influenza. Distinct barriers to influenza vaccination exist among racial/ethnic groups. Vaccination programs may benefit from addressing these specific and unique concerns. PMID- 17269311 TI - Effect of maternal HIV infection on child survival in Ghana. AB - The purpose of this study was to measure the association between maternal HIV infection and infant mortality in Ghana. Using a censored synthetic cohort life table based on the birth history of 3639 childbirths during 1999-2003 obtained from the interviews of a nationally representative sample of 5691 women age 15-49 in 6251 households in the 2003 Ghana Demographic and Health Survey. The survey collected demographic, socioeconomic, and health data of the respondents as well as obtained voluntary counseling test for HIV infection from all eligible women. The effects of maternal HIV status and other factors on infant mortality were estimated using multivariate survival regression analysis and the results are presented as Hazard Ratios (HR) with 95% confident interval (95% CI). Children born to HIV infected mothers were three times as likely to die during infancy as those born to uninfected mothers (HR = 3.01; 95% CI: 1.64, 5.50). Controlling for other factors affecting infant mortality further sharpens this relationship (HR = 3.51; 95% CI: 1.87, 6.61). Not receiving antenatal care, low birth weight, and living in households that use high pollution cooking fuels were associated with a higher risk of infant mortality. Maternal HIV status is a strong predictor of infant mortality in Ghana, independent of several other factors. The results of this study suggest that HIV/AIDS epidemic has had great impact on child well being and child survival. This impact tends to increase as the HIV/AIDS epidemic matures and infection in adults increases. PMID- 17269312 TI - Health risk behaviors in a unique population-first ring suburban adolescents. AB - This study aims to call attention to First Ring suburban communities as a unique and unrecognized population and to characterize health risk behaviors of adolescents within these communities. A risk behavior profile of the First Ring suburbs surrounding a large Midwestern city is presented and compared to the frequency of these behaviors in a national sample. In 2002, a representative sample of 3428 high school students from First Ring suburban communities in an urban county completed the Youth Risk Behavior Survey. A 20-item risk score composed of "current" risk behaviors was compiled in order to compare the relative number of risk behaviors exhibited by the First Ring schools to a 2001 national sample. Prevalence of individual behaviors was also determined and compared to data collected nationally. Prevalence was further subdivided by gender, race, and grade in order to explore risk groups within First Ring suburbs. Despite the perception that the "urbanization" of First Ring suburbs is synonymous with "urban" problems and risk behaviors, First Ring students reported significantly fewer current risk behaviors than did students nationally. Significant differences in behavior were found between First Ring and national gender and racial groups. Some patterns of behavior within gender and racial groups differed from national patterns. The commonly held presumption that First Ring suburbs are riskier for students due to increased urbanization of these communities appears unfounded. The contribution of these destructive misperceptions to social migration away from urban centers and the need for local data collection are discussed. PMID- 17269313 TI - Psychosocial factors associated with use of multivitamins by women of childbearing age. AB - To determine the association between psychosocial factors and use of multivitamins among women (18-40 years; N=3438) who were enrolled in Kaiser Permanente Health Plan in southern California. A telephone survey elicited information about multivitamins and psychosocial and demographic characteristics. The outcome variables were any and regular use (> or =4 times per week) of multivitamins. Four psychosocial factors were: perceived need to take multivitamins and perceived benefits, barriers, and locus of control. Data were analyzed using exploratory factor analysis and multivariate analyses that adjusted for age, race or ethnicity, marital status, education, and discussion of multivitamin use with a health care provider. Fifty one percent of women reported using multivitamins; of this group, 79% were regular users. After adjusting for several covariates, factors positively associated with any use of multivitamins were perceived need (odds ratio [OR] = 1.22; 95% confidence interval [CI] = 1.15 1.29), perceived benefit (OR = 1.15; CI 1.08-1.22); and perceived barriers had a negative association with any use (OR = 0.64; CI 0.59-0.68). When regular users were compared to irregular users in a multivariate analysis, regular use was positively associated with perceived benefits (OR = 1.13; 95% CI: 1.02-1.25) and negatively associated with barriers (OR = 0.47; 95% CI: 0.41-0.53). Women who were not advised by their providers about multivitamins were less likely to use them (OR = 0.43; 95% CI: 0.36-0.52) or to be regular users (OR = 0.68; 95% CI: 0.50-0.91). Results suggest that certain psychosocial factors as well as advice from a health care provider help women to make decisions about multivitamin use. PMID- 17269314 TI - Cigarette smoking, binge drinking, physical activity, and diet in 138 Asian American and Pacific Islander community college students in Brooklyn, New York. AB - Assessment of cigarette smoking, alcohol consumption, physical activity, and diet in the Asian American and Pacific Islander (AAPI) community has been neglected. A questionnaire was used to investigate these health risk behaviors in 466 students at an urban community college and results for the 138 AAPI study participants were compared to the 328 non-Asians. Results for AAPI study participants showed that twenty percent (20.3%) were current cigarette smokers and 7.7% smoked eleven or more cigarettes per day. Ten percent (10.7%) reported binge drinking on one to two days per month and 17.3% reported binge drinking on three or more days per month. With regard to physical activity, 28.8% participated in stretching, 23.6% in strength and toning, 29.4% in moderate exercise, and 25.4% in vigorous exercise. Results indicated that on the day preceding the survey, only 11.9% consumed five or more servings of fruits and vegetables, 88.4% ate no more than two servings of high-fat foods, and 37.6% consumed tofu, soymilk, or other soy food. AAPI study participants were more likely to frequently binge drink (p < .05), less likely to participate in strength and toning exercises (p < .05), and more likely to consume soy foods daily (p < .01) than non-Asian study participants. Recommendations are presented for health promotion program planning. PMID- 17269315 TI - [Morphological-ecological characters and growth patterns of main tree species leaves in urban forest of Shenyang]. AB - The study with statistic and multivariate analyses showed that the main meteorological factors affecting the growth and development rhythms of main tree species leaves in urban forest of Shenyang were > or = 5 degrees C accumulated temperature, accumulated sunshine hours, and mean temperature in the middle ten days of each phenological period. The meteorological factors needed by the tree species varied with their phenological period. Necessary low temperature and CI were required in germination period, and suitable WI and HI were needed in the growth period. The major quantitative morphological characters of 10 tree species in Shenyang urban forest were displayed in their leaf morphology and size, which decreased in the sequence of Lespedeza cyrtobotrya > Syringa oblata > Sophora japonica > Populus alba > Cornus alba > Lonicera maackii > Ligustrum obtusifolium > Fraxinus mandshurica > Prunus padus > Phellodondron amurense. As for the leaf area, it was decreased in the order of S. oblata > P. alba > P. amurense > P. padus > F. mandshurica > C. alba > L. cyrtobotrya > L. maackii > S. japonica > L. obtusifolium. The relationships of leaf length with leaf width, perimeter and area accorded with the model of y = ax(k), and the growth trend belonged to allometic type. The k value between leaf length and width of all test tree species except P. alba was lower than 1, and that between leaf length and perimeter was > 1 for P. amuresne, approximately 1 for P. alba, and < 1 for other tree species. As for the k value between leaf length and area, it was > 1 for all the tree species, with that of P. alba being 2. 1028. The increasing rate of leaf area was about 2 times higher than that of leaf length. An optimum regression assessment model of the 10 tree species leaf area was built and tested. PMID- 17269316 TI - [Genetic diversity of Sabina vulgaris populations at different succession stages]. AB - By means of random amplified polymorphic DNA markers, a molecular ecological study was made with Sabina vulgaris populations at 4 succession stages in Maowusu sandy grassland, aimed to reveal the relationships between molecular variation and succession stages. A total of 17 random primers were selected for amplification, and 190 repetitive loci were produced, of which, 173 were polymorphic. The data were analyzed by POPGENE 3. 2 Version 1. 31. The results showed that the genetic diversity of S. vulgaris populations was high, and changed with succession stages. The percentage of polymorphic loci in each S. vulgaris population ranged from 64.21% to 74.63%, with the highest in early succession stage Artemisia ordosica + S. vulgaris on semi-fixed sand dunes, and the lowest in sub-climax stage S. vulgaris on fixed dunes. The genetic differentiation among the populations was small (G(st) = 0.1761), and 82.39% of it was within the populations. Cluster analysis demonstrated that the populations at similar succession stage clustered together, suggesting that the genetic differentiation was closely related to succession stage. The genetic diversity indicated by Nei index ranged in 0. 2163 -0. 2564, and the gene flow (N(m) *) was 2.7972, indicating that more gene exchange occurred within the populations, which prevented the genetic differentiation among the populations at different succession stages. PMID- 17269317 TI - [Quantitative determination of the depth of edge influence on soil moisture in pepper-forest boundary of Minjiang River upper reaches]. AB - A typical pepper-forest boundary was selected in the arid valley of Minjiang River upper reaches, and the moisture content in 0-15 cm soil layer was determined by time-domain reflectometry (TDR) during drought, after rain, and different seasons. Moving split-window techniques (MSWT) was employed to detect the depth of edge influence (DEI) on soil moisture and its dynamic variation with time. The results showed that the changes of squared Euclidean distance (SED) curve on the graph tended to become stable when the window width reached 8 - 12, and DEI could be detected. The seasonal variation of soil moisture could be divided into three periods, i.e., rising period (January to April), peak period (May to October), and lessen period (November to December). DEI was smaller during drought, and increased after rain. The DEI on soil moisture ranged from 6 m in pepper field to 2 m in forest during drought and from 12 m in pepper field to 2 m in forest after rain, but ranged from 10 m in pepper field to 2 m in forest field within a year. DEI was different in different seasons, and was dynamic. Under such condition of soil moisture, the forest restoration from pepper land and the seedling planting were not ecologically reasonable. Reducing human disturbance and revegetating with natural shrubs and meadows could be more effective for vegetation conservation in the arid valley of Minjiang River upper reaches. PMID- 17269318 TI - [Effects of drought stress on photosynthesis physiology of Populus pseudo simonii]. AB - In this paper, the effects of drought stress simulated by PEG on the photosynthesis of Populus pseudo-simonii were monitored by gas exchange and chlorophyll fluorescence techniques. The results showed that in the early phase of drought stress, net photosynthetic rate (P(n)), transpiration rate (T(r)), stomata conductance (g(s)) , and intercellular CO2 concentration (C(i)) decreased with increasing stress, and the decrease of P(n) was mainly related to the decreased g(s). In the late phase, C(i) increased gradually, while F(v)/F(m) and F(v)/F(o) decreased significantly. POD activity increased in the early phase, but decreased in the late phase. All of these indicated that in the early phase of drought stress, stomata closure was the main factor limiting P. pseudo-simonii photosynthesis, while in the late phase, the main limiting factor was non stomatal. A short period of drought stress induced the increase of protective enzyme activity, but a longer exposure to the stress resulted in the decrease of PS II efficiency and POD activity. PMID- 17269319 TI - [Effects of color films shading on Phellodendron amurense seedlings biomass and primary nitrogen-assimilation enzyme activities]. AB - In this paper, greenhouse Phellodendron amurense seedlings were shaded with red, yellow, blue, and green films for 100 days, and their biomass, chlorophyll and soluble protein contents, and nitrate reductase and glutamine synthetase activities were determined. Compared with exposure under sunlight, color films shading decreased the seedlings biomass significantly. Plant height and stem diameter had the similar trend with plant biomass. Root/ shoot ratio was less affected by red and yellow films shading, while root biomass was decreased significantly under blue and green films shading. Leaf chlorophyll content was increased significantly under the shading with blue, green and red films, especially with blue film. Red film shading increased the chlorophyll a/b ratio, while blue film shading was in adverse. Under color films shading, soluble protein content and nitrate reductase and glutamine synthetase activities were significantly higher than the control. PMID- 17269320 TI - [Influence of measurement position on calculating pear tree stem sap flow]. AB - By the method of heat pulse, this paper studied the influence of different measurement positions on calculating the stem sap flow velocity and quantity of pear trees. The results showed that at definite depths, the directional variation of the volume fraction of water and wood was lower than the seasonal change of wood physical parameters. The directional and seasonal variation of the volumetric water and wood was 0.01 - 0.03 and 0 - 0.02, and 0.02 - 0.09 and 0.02 0.08, respectively. The sap flow velocity at definite depth, which was calculated by different depths wood physical parameters measured at the same time, had no significant difference, but that calculated by the same depth wood parameters measured at different time was significantly different. The sap flow quantity measured at the inner two points and four points was underestimated 1.5 and 4.9 times of that measured at the outer corresponding measurement positions, relative to the estimation obtained from a multi-point measurement. The sap flow quantity measured by four-point at the position of 0 - 0.6 from the cambium could represent the water consumption of whole tree. PMID- 17269321 TI - [Effects of land use change on soil organic carbon and microbial biomass carbon in Miyaluo forest area]. AB - In last century, extensive areas of native vegetation in the Miyaluo forest area of Western Sichuan were converted into agricultural land and forestland. To assess the effects of land use change on soil organic carbon (SOC) and microbial biomass carbon (MBC), soil samples were taken from Abies faxoniana wildwood, Picea likiangensis var. balfouriana plantations established in 1960s and 1980s, and cropland, and their SOC and MBC contents were determined. The results showed that A. faxoniana wildwood had the highest SOC and MBC contents, followed by the P. likiangensis var balfouriana plantations established in 1960s and 1980s, and cropland. The SOC content was 83%, 53% and 52% lower, and the MBC content was 23%, 25% and 21% lower in cropland than in wildwood and in the plantations established in 1960s and 1980s, respectively. SOC and MBC contents decreased with increasing soil depth. There existed significant correlations of these two indices with soil total N, hydrolysable N and available P, indicating that both SOC and MBC could be used as the important indicators to measure the changes of soil quality. PMID- 17269322 TI - [Genetic diversity and clonal structure of Potamogeton malaianus populations]. AB - By using inter-simple sequence repeat (ISSR) makers, this paper studied the genetic diversity and clonal structure of two Potamogeton malaianus populations growing in different habitats of two lakes in the middle reaches of Yangtze River. With six primers selected, a total of 40 fragments, of which 30 (75.0%) were polymorphic, were obtained from 106 individuals. This species showed a high genetic diversity, with Nei's gene diversity of H = 0.2471 and Shannon' s information index of I = 0.3736. A low degree of population differentiation (G(st) = 0.0861) was found between the two populations, and a very high clonal diversity (D = 0.9917) was detected, according to the analysis based on the polymorphic loci. No common genotypes were found among the individuals from the two populations, showing a great clonal differentiation between them. The spatial distribution pattern of P. malaianus genets showed 'guerilla' architecture, and the clonal distance of the population in lake center (3.0 - 31.5 m) was significantly larger than that in lakeshore (2.4 - 6.7 m). PMID- 17269323 TI - [Diurnal change of photosynthetic characteristics of native Vetiveria zizanioides in western Guangdong]. AB - The determinations on the photosynthetic parameters of native Vetiveria zizanioides in Western Guangdong in autumn showed that the net photosynthetic rate (P(n)) of V. zizanioides had a diurnal change with two peaks, transpiration rate (T(r)) and stomatal conductance (G(s)) were similar with P(n), while intercellular CO2 concentration (C(i)) was in adverse. There was a significant positive correlation between P(n) and photosynthetic active radiation (PAR) (P < 0.01) , T(r) and PAR (P < 0.01), air temperature (T(a)) and relative humidity (RH) (P < 0.01), and G(s) and T(a) (P < 0.05). Same environmental factors had different effects on P(n), T(r) and G(s), and PAR had most intensive effect on the photosynthesis of V. zizanioides. Among the test photosynthetic parameters, T(r) was most sensitive to the environmental factors. PMID- 17269324 TI - [Estimation of sensible and latent heat fluxes of typical steppe in Inner Mongolia based on variational method]. AB - Based on the observation data and the export data of microclimatic gradient system during growing and non-growing seasons of Stipa krylovii grassland in Inner Mongolia, this paper investigated the accuracy of variational method (VT) on estimating the surface heat fluxes of grassland. The results showed that the changes of sensible and latent heat fluxes estimated by VT were consistent with those obtained by open-path eddy covariance method (EC), and the fluxes estimated by VT could better satisfy the surface energy balance equation. The sensible heat fluxes (H) from VT were mostly higher than the corrected fluxes from EC, and the values and their difference from these two methods all got the maximum at twelve o'clock in daytime, and were close in nighttime. The variations of latent heat fluxes from VT lagged behind those from EC. VT could solve the problems that the conventional Bowen ratio energy balance method (BREB) was computationally unstable and produced spurious large values when the Bowen ratio was in vicinity of -1. Compared with EC and BREB, VT was more of rationality and stability. PMID- 17269325 TI - [Dynamics of soil microbial biomass and dissolved organic carbon and nitrogen under flooded condition]. AB - With reddish yellow soil (RYS) and alluvial purple soil (APS), the two typical paddy soils in the Dongting Lake floodplain of China as test soils, an incubation test was conducted at 25 degrees C to study the dynamic changes of soil microbial biomass and dissolved organic carbon and nitrogen under flooded condition. Three treatments were installed, i.e., control (CK), ammonium sulfate (N), and rice straw powder plus ammonium sulfate (S-N). The results showed that during incubation, soil microbial biomass carbon (SMBC), soil microbial biomass nitrogen (SMBN), soil dissolved organic carbon (SDOC), and soil dissolved organic nitrogen (SDON) reached their maximum initially, decreased thereafter, and tended to be stable. After amending the substrates to the two soils, the averages of SMBC to soil total carbon, SMBN to soil total nitrogen, SDOC to soil total carbon, and SDON to soil total nitrogen were 2% - 3%, 2% - 3%, 1% or so, and 5% - 6%, respectively. In the two soils, the peak values of SMBC in treatment N and those of SMBN, SDOC and SDON in treatment S-N were the highest, while those of SMBC in treatments N and S-N had no significant difference. The peak values of SMBN, SDOC and SDON in RYS were significantly different between treatments N and S-N, while no significant difference was observed between the peak values of SMBN and SDOC in APS, because the fertility of RYS was lower than that of APS. In the first 7 days of incubation, SMBC/SMBN ratio was < 10, while after 14 days of incubation, this ratio was higher in treatment N than in treatment S-N at the same time in the same soil. The SDOC/SDON ratio in all treatments was the highest at the 3rd d, and the lowest at the 28th d of incubation. PMID- 17269326 TI - [Optimal chemical fertilizer application rate accorded with local economic and ecological benefits]. AB - This paper studied the exterior cost of applying chemical fertilizer on the farmland in Dongting Lake area, one of the main foodstuff production regions in China, aimed to search for an optimal chemical fertilizer application rate accorded with local economic and ecological benefits. The exterior cost was estimated by the method of economic and environmental evaluation, while the optimal application rate was calculated based on Exterior Diseconomy Theory and by using production function model, with both ecological and farmers' economic benefits considered. The results showed that in 2002, the exterior cost of inappropriately applying chemical fertilizer was about 1.35 x 10(8) yuan, equivalent to 0.3 yuan x kg(-1) fertilizer N. Under current situation of test area, the optimal application rate of chemical fertilizer should be 208.26 - 210.65 kg x hm(-2), and the corresponding foodstuff supply would be 5528 - 5539 kg x hm(-2). However, the actual fertilizer application rate in 2002 exceeded the optimal one. A suggestion was made to impose tax for the environmental pollution of over-using chemical fertilizer. PMID- 17269327 TI - [Effects of nitrogen fertilization on leaf photosynthesis and respiration of different drought-resistance winter wheat varieties]. AB - Under field condition, this paper measured the leaf gas exchange parameters and photosynthetic pigments content of different drought-resistance wheat varieties at all growth stages, with their responses to different nitrogen fertilization levels studied. The results showed that in treatment N180, the leaf G(s), P(n), and total photosynthetic pigments content of dry land varieties increased by 43.75%, 18.54% and 49.66% , while those of watered land varieties increased by 12.12% , 20.88% and 29.25%, respectively, compared with control. On the contrary, the respiration rate of dry land and watered land varieties decreased by 4.8% and 4.5%, respectively. Nitrogen supply accelerated the photosynthetic carbon assimilation, because the gas exchange capacity and photosynthetic pigments content increased while the respiration rate decreased with increasing nitrogen supply. The difference in photosynthetic capacity between different winter varieties was mainly dependent on non - stomatal factors. The dry land varieties had higher capacities of light energy absorption and photosynthetic carbon assimilation, because they had higher leaf photosynthetic pigments content but lower respiration rate. Compared with watered land varieties, dry land varieties had an 8.9% decrease of respiration rate and a 14.12% increase of P(n). At the same growth stage, the photosynthetic and respiration rates in the control varied consistently, while in treatments N180 and N360, the photosynthetic rate increased but the respiration rate decreased. Nitrogen fertilization promoted the absorbed light energy allocating to the process of photosynthetic carbon assimilation. It could be concluded that nitrogen supply was favorable to the improvement of winter wheat drought-resistance, because it could improve leaf gas exchange capacity, increase leaf photosynthetic pigments content, and optimize the allocation of absorbed light energy. PMID- 17269328 TI - [Allelopathic potential and physiological mechanism of Oryza sativa L. under phosphorus deficiency stress]. AB - In this paper, allelopathic rice PI312777 (PI) and non-allelopahtic rice Lemont (Le) were grown in the nutrient solution with two levels of phosphorus (P) supply, and their allelopathic effects on Echinochloa crus-galli L. were studied. The results showed that under phosphorous deficiency stress, the inhibitory effect of PI on E. crus-galli root growth had an obvious increase. After growing in the nutrient solution with low P supply (0.5 mg x L(-1)) for 5, 10 and 15 days, the inhibitory rate of PI on E. crus-galli root dry matter increased by 5.64%, 3.89% and 12.13%, respectively, while that of Le did not show the same trend, compared with normal P supply. With low P supply for 5, 10 and 15 days, PI allelopathic effect on the leaf POD activity of E. crus-galli increased by 20.19%, 15.47% and 6.68%, IAAoase activity increased by 18.08%, 17.71% and 12.50%, while NR activity increased by 13.89%, 18.60% and 2.10%, respectively, suggesting that under P deficiency, PI enhanced its allelopathic potential through two pathways, i.e., to increase the weed POD and IAAoase activities to slow down its growth rate, and to decrease the weed NR activity to affect its N uptake. PMID- 17269329 TI - [Effects of different mulches on rhizosphere temperature, growth, and physiological properties of fluecured tobacco]. AB - With greenhouse plastic film, rice straw plus greenhouse plastic film, soil mulching plastic film, rice straw, rice straw plus sun-shading net, and sun shading net as test mulches, this paper studied their effects on the rhizosphere temperature, growth, and physiological properties of flue-cured tobacco. The results showed that after mulching for 22 days, the accumulative rhizosphere temperature at the depth of 5 cm was the highest (424.75 degrees C) for greenhouse plastic film and the lowest (378.75 degrees C) for rice straw plus sun shading net, while that at the depth of 15 cm was the highest (396.75 degrees C) for greenhouse plastic film and the lowest (368.31 degrees C) for sun-shading net. With the increase of accumulative rhizosphere temperature, the dry weight of above- and underground parts, photosynthesis, and root vigor of flue-cured tobacco tended to increase, and at the 10th day after mulches removal, root biomass had the largest increment in the treatment of soil-mulching plastic film and the smallest increment in the treatment of rice straw plus sun-shading net. PMID- 17269330 TI - [Seasonal fluctuation of macrobenthos community in Jiuduansha intertidal wetland of Yangtze River Estuary]. AB - From November 2004 to October 2005, an investigation was made on the seasonal fluctuation of macrobenthos community in the Jiuduansha intertidal wetland of Yangtze River Estuary, with the correlations between this fluctuation and sediment factors studied. 864 samples were collected seasonally from 216 sites in 7 sampling transects. A total of 30 species were identified, mainly belonging to Mollusca, Annelida, Crustacea and insect. The dominant species were Stenothyra glabra, Assiminea violacea, Potamocorbula ustulata, Glaucomya chinensis, and Ilyrplax deschampsi. In spring, macrobenthos had the highest density and biomass and the richest diversity, but in summer, the density and biomass were the lowest, the diversity was on a lower level, and the distribution was uneven. There were no significant differences in the species number and biomass between autumn and winter, but the density was higher in winter than in autumn. In spring, summer and autumn, the species number, density, and biomass of macrobenthos had no significant correlations with sediment factors, but in winter, macrobenthos density had significant correlations with the humidity and organic matter content of sediment. PMID- 17269331 TI - [Behavioral patterns of wild-caught and captive-bred male musk deer]. AB - By the method of focal sampling and continuous recording, a comparative study was made on the behavioral patterns of 23 captive alpine musk deer (Moschus sifanicus) , among which, 17 deer were wild-caught (WC), and 6 deer were captive bred (CB). The results showed that owing to the same enclosure facilities and managing system, there was no essential difference in the behavioral modes between WC and CB, but WC exhibited more collision behavior than CB (P < 0.05) because of the differences in capture, lactation, and contact with other baby deer. Male deer showed lower bedding (P < 0.05), ingestion (P < 0.05) and ruminating (P < 0.05), but more moving (P < 0.05) at mating season, compared with those at non-mating season. Furthermore, male deer expressed more scent marking through intensive tail-rubbing and urination-defecation, and accordingly, the behaviors of scent collecting such as environment sniffing and anogenital exploring were expressed more stronger, though the differences were not significant (P > 0.05). PMID- 17269332 TI - [Community structure and its dynamics of predatory arthropod in jujube orchards intercropped with different herbage species]. AB - By using community structural characteristic indices and principal component analysis, this paper studied the community structure and its dynamics of predatory arthropod in the jujube orchards intercropped with Astrugalus complanatus, Trifolium repen, Lotus comiculotus, and Medicago sativa. The results showed that in all test jujube orchards, spider and predatory insects were the predominant components of the predatory arthropod community, and their relative abundances were 48.3% - 52.7% and 38.8% - 44.4% , respectively. There were significant differences (P < 0.05) in the mean density, diversity, and evenness of the most common predatory arthropod groups in the jujube orchards intercropped with different herbage species, with the sequence of intercropped with Lotus comiculotus > Medicago sativa > Astrugalus complanatu > Trifolium repens, but for dominant concentration index, the sequence was intercropped with Trifolium repens > Astrugalus complanatu > Medicago sativa > Lotus comiculotus. The average density of predatory spiders was significant higher (P < 0.05) than that of predatory insects in all test jujube orchards. The individuals of Coccinellidae, Pentatomidae, inoccllidae, Chrysopidae, Thomisidae, Araneidae and Phytoseiidae played the dominant role in the community. PMID- 17269333 TI - [Potential establishment areas of Solenopsis invicta in China: A prediction based on GIS]. AB - Based on geographic information system (GIS), the potential establishment areas of Solenopsis invicta Buren in China were predicted. The days above threshold temperature and the number of degree-days were used as main determining factors, while annual precipitation and altitude were used as limiting factors. By using the Kriging spatial interpolation function in GIS software, the potential establishment area was divided into four categories, i.e., most suitable, suitable, mildly suitable, and unsuitable. The most suitable area was in the greater part of Guangdong, central and southern Guangxi, small part of southern Yunnan, Hainan, Taiwan, Hong Kong, and Macao, suitable area was in southern Yunnan, northern Guangxi and Guangdong, southern Henan, western Anhui, greater part of Zhejiang, central and eastern Hubei, Chongqing, Hunan, Jiangxi, and Fujian, mildly suitable area was in the greater parts of Anhui and Henan, central and eastern Hebei and Shandong, Beijing, Tianjian, central and northern Jiangsu, northwestern Zhejiang and Hubei, southern Shanxi, eastern Sichuan, central and western Guizhou, and small part of central Yunnan, and unsuitable area was in the greater parts of northwest, northeast, and north China. PMID- 17269334 TI - [Aromatic constituents in fresh leaves of Lingtou Dancong tea under Basilepta melanopus Lefevre stress]. AB - The study showed that under different degrees of Basilepta melanopus Lefevre stress, the kinds of aromatic constituents in the fresh leaves of Lingtou Dancong tea plant increased evidently, being the most (36 kinds) under medium stress. With the increase of the stress, the contents of 9 aromatic constituents like 1,6 methylene annulene increased, whereas those of 8 constituents as linalool decreased. Light stress induced the appearance of 4 aromatic constituents like 2 methyl hexadecane, while medium stress induced that of 6 constituents as H1 docosanol. Different degrees of B. melanopus stress could induce the synthesis of 23 aromatic constituents like 1,6-methylene annulene, but inhibit the formation of 6 constituents as nonanal. PMID- 17269335 TI - [Genetic diversity of Melampsora larici-populina]. AB - By using ITS - nrDNA-RELP, ITS sequencing, and RAPD molecular marker, this paper studied the genetic diversity of 11 isolates in 5 races of Melampsora larici populina from different regions. The results indicated that the genetic differentiation of M. larici-populina was correlated to its geographical distribution, which could be grouped into northern and western geographic populations, and the latter could be grouped into high-mountain forest ecologic type (HMF) and western plain ecologic type (WPL). The genetic differentiation of the race was not always corresponded with the pathogenic one. T test manifested that the genetic diversity of the 5 races had no statistic difference in RAPD markers, and the diversity index of HMF was 0.5172, being slightly higher than that of WPL (0.5089). The ITS sequence of ribosome DNA was strictly conservative, and not suitable for the genetic diversity study of M. larici-populina intra species populations. PMID- 17269336 TI - [A highly effective extraction method for PCR analysis of soil microbial DNA]. AB - In this paper, soil microbial DNA was extracted by cetyltrimethyl ammonium bromide (CTAB) -lysosome-protease K-freezing thaw lysing, and precipitated and purified with PEG 8000. The results showed that this method was simple and effective for the PCR analysis of soil microbial DNA. To effectively remove humid acid, test soil was pre-washed by polyvinylpyrrolidone (PVP) buffer and added with CaCl2 and bovine serum albumin (BSA). The precipitation with PEG8000 could obtain high quality DNA, and the lysing with (CTAB) -lysosome-protease K-freezing thaw could get large fragment DNA. Using this method, the yield of soil microbial DNA under Heptacodium miconioides forest was 9.22 microg x g(-1), with A260/A080 being 1.65. The extracted DNA was proved to be successfully used for further PCR amplification and amplified ribosomal DNA restriction analysis (ARDRA). The optimal template DNA concentration in PCR amplification was 0.67 ng x microl(-1). The establishment of this simple, rapid and effective method made it possible to study the molecular ecology of soil microbes in a large scale. PMID- 17269337 TI - [Isolation, purification, and phosphate-solubilizing capability of phosphorous bacteria in West Lake sediment]. AB - By using solid culture media containing organic and inorganic phosphorus, six strains of phosphorous bacteria in West Lake sediment were isolated and purified, among which, two strains coded as OP1 and OP2 could decompose lecithin, and the other four coded as NOP1, NOP2, NOP3 and NOP4 could dissolve inorganic phosphate. OP1, OP2 and NOP3 had a stronger phosphate-solubilizing capability, followed by NOP4, while NOP1 and NOP2 lost this capability after isolation and purification. The water-soluble P concentration in the culture media inoculated with OP1 , OP2 and NOP3 increased 38.53, 64.53 and 54.06 fold, respectively, compared with the control. PMID- 17269338 TI - [Isolation and identification of a phenanthrene-degrading bacterial strain]. AB - Through selective enriched culture, a phenanthrene-degrading bacterial strain was isolated from the oil-contaminated soil in Shenfu irrigation area of Shenyang, Northeast China. The morphological and physiological-biochemical identification, 16S rDNA sequence analysis, and phylogenetic study showed that this strain was belonged to genus Acinetobacter and named as Acinetobacter sp. L2, and closest to Acinetobacter sp. DG880 [AY258108]. It could use phenanthrene as the sole carbon source. After 7 days culture, the degradation rate of phenanthrene was 96.3%. According to the activity of catechol 2,3-dioxygenase, the strain probably had phenanthrene-degrading genes. PMID- 17269339 TI - [Field inoculation effect of AM fungi on Tibet plateau Stipa bungeana grassland]. AB - A field experiment was conducted on the Tibet plateau Stipa bungeana grassland to investigate the effects of arbuscular mycorrhizal fungi (AMF) inoculation on S. bungeana growth and its phosphorus uptake, and on soil microbial communities under unsterilized condition. The results showed that AMF inoculation increased the AMF spore density, infection rate and infection intensity in rhizosphere soil significantly, but had less effect on arbuscule richness. The infection rate of AMF increased with its increasing spore density, and the plant dry weight and P uptake of S. bungeana increased significantly with AMF infection rate. Similar results were observed in S. bungeana root dry weight and its P content. AMF inoculation increased the acid and alkaline phosphatase activities and bacterial biomass in rhizosphere soil, but had less effect on fungal and actinomyces communities. The infection effect of AMF varied with inoculation treatments, being in the sequence of Glomus mosseae + G. intraradices + Scutellospora calospora > G. mosseae + G. aggregatum > Glomus sp. > G. mosseae > G. mosseae + G. etunicatum + G. intraradices + S. erythropa > G. geosporum. PMID- 17269340 TI - [Electrical conductivity as an indicator of hydrological characteristics in catchment scale]. AB - In this paper, the hydrological characteristics of Heishui River in Sichuan Province were studied, with electrical conductance (EC) as the main indicator. A total of 10 sites were selected on the branch and main streams, and the EC determinations were made at low-flow and level-flow periods. The results showed that EC value was significantly different among test sites, but had no significant difference between the two sampling times. The t-test on the EC values of different sites at two sampling times also showed the similar pattern, indicating that the index EC could be helpful for distinguishing hydrological period and indexing river characteristics, and the contribution of branch stream to its neighboring main stream could be estimated by the EC. Using EC as a characteristic index of hydrological temporal-spatial changes could provide a convenient way for the further studies of catchment hydrology. PMID- 17269341 TI - [Statistical self-similarity of channel networks in Zagunao River catchments]. AB - Self-similarity of channel networks is an important field in hydrologic scaling research, while the statistical self-similarity of channel networks is to study the similarity of the probabilistic distribution functions of network parameters at different scales. In this paper, the relationships between the entire network and the streams of the same Horton-Strahler order were derived in terms of the probabilistic distribution of network parameters, and empirical tests were performed by using the DEM data of Zagunao River catchments. The results of Kolmogorov-Smirnov Two-Sample test showed that the derived equations fitted the empirical data well, suggesting that the relationships between the entire network and the streams of the same Horton-Strahler order were of complicated cascade rather than "simple scaling". PMID- 17269342 TI - [Effects of human engineering activities on permafrost active layer and its environment in northern Qinghai-Tibetan plateau]. AB - With disturbed and undisturbed belts during the construction of Qinghai-Tibet highway as test objectives, this paper studied the effects of human engineering activities on the permafrost ecosystem in northern Qinghai-Tibetan plateau. The results showed that the thickness of permafrost active layer was smaller in disturbed than in undisturbed belt, and decreased with increasing altitude in undisturbed belt while no definite pattern was observed in disturbed belt. Different vegetation types had different effects on the thickness of permafrost active layer, being decreased in the order of steppe > shrub > meadow. In the two belts, altitude was the main factor affecting the vertical distribution of soil moisture, but vegetation type was also an important affecting factor if the altitude was similar. Due to the human engineering activities, soil temperature in summer was lower in disturbed than in undisturbed belt. PMID- 17269343 TI - [Remote sensing information model for desertification evaluation of Keerqin sandy land]. AB - By using remote sensing information model, this paper quantitatively retrieved the main factors for desertification evaluation of Keerqin sandy land, which included vegetation cover, biomass, and soil moisture content. The occupation ratio of bare sandy land was obtained by using linear mixed spectrum model. Every image pixel could be used to acquire the indices of all evaluation factors. Based on the current methods of desertification assessment, the quantitative remote sensing information model on the basis of the pixel was built, and the distribution map of desertification degree was plotted. The precision of the model calculated by selecting 60 in situ sample data reached 91.7%, suggesting that it was reliable and scientific to evaluate the desertification degree by using this model. PMID- 17269344 TI - [Integrative study of Guangdong ecological-economic system based on emergy analysis]. AB - Based on the theories and methodologies of emergy, a quantitative analysis on the development sustainability of Guangdong Province in 1990-2003 was made from the aspects of environment, society, and economy at system and subsystem levels. The results showed that Guangdong Province was of developed provinces in China, and highly depended on the input of feedback emergy. Though the pollution control was fruitful, the increasing environmental loading was still not relieved on the whole, and the development sustainability was relatively low. This Province was increasingly relied on international market, and actually, under the status to the bad in exporting primary products and importing high-tech products. To improve the development sustainability of this Province, more concerns should be paid on improving the added values of products, making full use of the natural and labor resources in its underdeveloped area, and further bringing the economic superiority of its developed area into play. PMID- 17269345 TI - [Dynamic changes of ecological footprint and ecological capacity in Fujian Province]. AB - The analysis on the dynamic changes of ecological footprint and ecological capacity in Fujian Province showed that in 1999-2003, the ecological footprint per capita in the Province increased from 1.428 hm2 to 1.658 hm2, while the ecological capacity per capita decreased from 0.683 hm2 to 0.607 hm2, with an increased ecological deficit year after year. The contradiction between the ecological footprint and ecological capacity pricked up gradually, and the ecological environment was at risk. There existed a severe imbalance in the supply and demand of ecological footprint per capita. The main body of the demands was grassland and fossil fuel, accouting for 55.74% - 63.43% of the total, while their supply only occupied 0.77% - 0.82% and next to nothing of the ecological capacity per capita, respectively. As a whole, the ecological footprint per ten thousand yuan GDP declined in the five years, indicating that the resources use efficiency in the Province was improved gradually. Based on the analysis of the present situation of the economic development and resources distribution in the Province, the strategies on reducing ecological deficit were put forward. PMID- 17269346 TI - [Air negative charge ion concentration and its relationships with meteorological factors in different ecological functional zones of Hefei City]. AB - Air negative charge ion concentration (ANCIC) has a close relationship with air quality. The observations on the ANCIC, sunlight intensity, air temperature, and air relative humidity in different ecological functional zones of Hefei City from 2003 to 2004 showed that the diurnal change pattern of ANCIC was of single peak in sightseeing and habitation zones, dual peak in industrial zone, and complicated in commercial zone. Different ecological functional zones had different appearance time of their daily ANCIC extremum. The diurnal fluctuation of ANCIC was in the order of commercial zone > industrial zone > habitation zone and sightseeing zone. The annual change pattern of ANCIC in these zones was similar, being the highest in summer and lowest in winter, and the mean annual ANCIC was 819, 340, 149 and 126 ions x cm(-3), respectively. The most important meteorological factor affecting the ANCIC in Hefei City was air relative humidity, followed by sunlight intensity and air temperature. There was an exponential relationship between ANCIC and air relative humidity. PMID- 17269347 TI - [Comprehensive evaluation of eco-tourism resources in Yichun forest region of Northeast China]. AB - By using analytical hierarchy process (AHP) and Delphi method, a total of 30 representative evaluation factors in the aspects of tourism resources quantity, environmental quantity, tourism conditions, and tourism functions were chosen to build up a comprehensive quantitative evaluation model to evaluate the eco tourism resources of Yichun forest region in Northeast China. The results showed that in Yichun forest region, the natural eco-tourism resources were superior to the humanity resources. On the regional distribution of favorable level eco tourism resources quantity, 4 sites were very prominent, i.e., north (Jiayin) center (Yichun) -east (Jinshantun) -south (Tieli). As for the distribution of eco tourism resources type, it was basically in the sequence of north (Jiayin, Tangwang River, Wuying) -center (Yichun, Shangganling) -east (Jinshantun, Meixi) south (Teli, Dailing). Based on the above analyses, Yichun forest region could be divided into four tourism areas, i.e., the south, the east, the central, and the north. Aimed at the special features of each area, the initial development directions were introduced. PMID- 17269348 TI - [Effects of soil moisture and temperature on N2O production rate of meadow grassland soil]. AB - With incubation test, this paper studied the effects of soil moisture and temperature on the N2O production rate of meadow grassland chernozem in Inner Mongolia. The results showed that soil moisture had a significant effect on the N2O production rate, with a non-linear relationship between them. Soil temperature had less effect than soil moisture. Their effects on the test soil N2O production rate at different growth stages could be described as a multi order polynomial relationship y = ax3 + bx2 + cx + d, where a, b, c and d were the constants. PMID- 17269349 TI - [Responses of Onobrychis viciaefolia Scop and soil nitrogen contents to elevated atmospheric CO2 concentration]. AB - The effects of elevated CO2 on terrestrial ecosystem processes are highly related to the N cycling in the ecosystem. In two closed chambers with different CO2 concentration (ambient CO2 355 - 370 micromol x mol(-1), and elevated CO2 700 micromol x mol(-1)), pot experiments were conducted to study the responses of Onobrychis viciaefolia Scop and soil nitrogen contents to elevated CO2. The results showed that compared with ambient CO2, elevated CO2 increased the plant dry biomass by 25.1% (P < 0.01), but decreased the plant N concentration by 25.3% (P < 0.001), resulting in little change of total plant N. After three months experiment, soil total N, NO3 (-) -N and NH4 (+) -N under both ambient and elevated CO2 conditions decreased, while soil microbial biomass N increased significantly. Soil NH4 (+) -N concentration had little difference under ambient and elevated CO2 conditions, but under elevated CO2 condition, soil NO3 (-) -N concentration decreased significantly, while microbial biomass N increased significantly. By the end of the experiment, the total N content of whole soil plant ecosystem had a slight increase, especially under elevated CO2 condition, which was probably due to the higher N-fixation capability of O. viciaefolia Scop under CO2 enrichment. PMID- 17269350 TI - [Effect of free-air CO2 enrichment (FACE) on leaf nitrate reductase activity of Oryza sativa L. cultivar Wuxianjing 14]. AB - With the target CO2 concentration of FACE plots being 200 micromol x mol(-1) above that in ambient air, this paper studied the effect of free-air CO2 enrichment (FACE) on leaf nitrate reductase activity (NRA) of Oryza sativa L. cultivar Wuxianjing 14. The results showed that FACE obviously increased the NRA of functional leaves at all growth stages, with an average increment of 50%, 20%, 60%, 80% and 30% at the stages of jointing, booting, heading, 10 after heading, and 20 days after heading, respectively, showing a pronounced effect at jointing, heading and 10 days after heading. Nitrogen application rate also had an obvious effect on the absolute value of NRA in functional leaves under FACE condition. The magnitude of NRA in three nitrogen treatments was in the order of normal nitrogen (NN) > low nitrogen (LN) > high nitrogen (HN) at jointing stage, HN > NN > LN at both booting and heading stages, and NN > HN > LN at both 10 days and 20 days after heading, respectively. The interactive effect of FACE and N supply on NAR varied with the growth stage of Wuxianjing 14, being very significant or significant at the stages of jointing and 20 and 10 days after heading, but not significant at booting and heading stages. PMID- 17269351 TI - [Toxic effects of 1,2,4-trichlorobenzene on rice seed germination and seedling growth]. AB - By the method of water culture, this paper studied the effects of 1,2,4 trichlorobenzene (1,2,4-TCB) on the seed germination and seedling growth of rice, with the chlorophyll, protein and proline contents and cytomembrane permeability of seedling leaf measured. The results showed the seed germination rate and vigor index were decreased with increasing concentration of 1,2,4-TCB, showing a definite dose-response relationship, and the seedling growth and root length were inhibited, showing definite time-response and dose-response relationships. The chlorophyll a, chlorophyll b, total chlorophyll, and protein contents in seedling leaf decreased with increasing concentration of 1,2,4-TCB, while the free proline content and cytomembrane permeability had a sharp increase when the concentration of 1,2,4-TCB was higher than 15 mg x L(-1). All of these suggested that the damage of rice seedling was a complicated process, which might be related to the structural and functional damage of cellular membrane, protein, and organelles. PMID- 17269352 TI - [Modeling of carbon cycling in terrestrial ecosystem: a review]. AB - Terrestrial carbon cycling is one of the important issues in global change research, while carbon cycling modeling has become a necessary method and tool in understanding this cycling. This paper reviewed the research progress in terrestrial carbon cycling, with the focus on the basic framework of simulation modeling, two essential models of carbon cycling, and the classes of terrestrial carbon cycling modeling, and analyzed the present situation of terrestrial carbon cycling modeling. It was pointed out that the future research direction could be based on the biophysical modeling of dynamic vegetation, and this modeling could be an important component in the earth system modeling. PMID- 17269353 TI - [Connotation of ecological integrity and its assessment methods: a review]. AB - Ecological integrity is the capability to support and maintain a balanced, integrative and adaptive biologic system, having the full range of elements and processes expected in the natural habitats of a region. Assessment of ecological integrity has great significance for preventing sensitive nature habitats from human disturbance. The theory of dissipative structures suggests that the stressors from human activities, as well as the biological, physical and chemical integrity and ecosystem function that reflect the ability of self-organizing, can well indicate the integrity of an ecosystem. This paper summarized the experiential indicators for assessing the integrity of aquatic and terrestrial ecosystems and the stressors from human disturbance, and discussed the methods for selecting priority indicators and comprehensive assessment in actual assessment programs. The prospects of further study were discussed, according to some issues existed in published researches. PMID- 17269354 TI - [Research advances in soil organic carbon and its fractions under different management patterns]. AB - Soil organic carbon can reflect soil quality and soil health, and is one of the hotspots in related researches at home and abroad. This paper reviewed the research results on the fractionation of soil organic carbon, with the focus on the dynamics of soil organic carbon and its fractions in their decomposition, accumulation, content, storage, and allocation proportion under different land use type and management pattern. Some related issues and further research directions were discussed. PMID- 17269355 TI - [Roles of organic acid metabolism in plant adaptation to nutrient deficiency and aluminum toxicity stress]. AB - Organic acids not only act as the intermediates in carbon metabolism, but also exert key roles in the plant adaptation to nutrient deficiency and metal stress and in the plant-microbe interactions at root-soil interface. From the viewpoint of plant nutrition, this paper reviewed the research progress on the formation and physiology of organic acids in plant, and their functions in nitrogen metabolism, phosphorus and iron uptake, aluminum tolerance, and soil ecology. New findings in the membrane transport of organic acids and the biotechnological manipulation of organic acids in transgenic model were also discussed. This novel perspectives of organic acid metabolism and its potential manipulation might present a possibility to understand the fundamental aspects of plant physiology, and lead to the new strategies to obtain crop varieties better adapted to environmental and metal stress. PMID- 17269356 TI - [Arbuscular mycorrhizal bioremediation and its mechanisms of organic pollutants contaminated soils]. AB - Arbuscular mycorrhiza (AM), the symbiont of arbuscular mycorrhizal fungi (AMF) and host plant root, has been proved to be able to improve soil structure and enhance the plant resistance to environmental stress. There are more than 170 kinds of AMF worldwide. Recently, the promoted degradation of organic pollutants in soils in the presence of AM was observed, and AM bioremediation (AMB) is becoming a promising and perspective remediation technique for organic pollutants contaminated soils. This paper reviewed the research progress on the AMB of soils contaminated by typical organic pollutants such as polycyclic aromatic hydrocarbons, PAEs, petroleum, and pesticides. The mechanisms of AMB mainly include the metabolism of organic pollutants by AM fungi, the degradation of these pollutants by the enzymes derived from AM exudation and by the enhanced root exudation and rhizospheric microbial activity in the presence of AM, and the removal of the pollutants by plant uptake and accumulation. As a new approach for the remediation of contaminated soils, some aspects involved in AMB, e.g., the screening of high efficient AM fungi, efficacy of co-existing AM fungi, soil ageing, and plant uptake of organic pollutants from soils in the presence of AM, still need to be further investigated. PMID- 17269357 TI - [Effects of elevated CO2 on soil hydrolase activities associated with Pinus koraiensis seedlings]. AB - In this study, Pinus koraiensis seedlings were grown under elevated CO2 (500 and 700 micromol x mol(-1)), and the hydrolase activities in 0 - 10 cm soil layer were determined. The results showed that compared with those under ambient condition, the activities of soil protease, urease, amylase and phosphatase under elevated CO2 increased significantly, while invertase activity decreased significantly. Different concentration of elevated CO2 had different effects on soil hydrolase activities. 500 micromol CO2 x mol(-1) had more significant effect on soil protease and phosphatase activities, while 700 micromol CO2 x mol(-1) had more significant effect on soil urease, amylase, and invertase activities. PMID- 17269358 TI - [Immobilization of introduced bacteria and degradation of pyrene and benzo(alpha) pyrene in soil by immobilized bacteria]. AB - In this study, introduced bacteria were applied in the bioremediation of pyrene and benzo (alpha) pyrene in organic pollutants-contaminated soils, aimed to test whether it was feasible to introduce bacteria to environmental engineering. Three introduced bacteria were immobilized separately or together to degrade the pyrene and benzo (alpha) pyrene in soil, taking dissociated bacteria as the control, and comparing with three indigenous bacteria. The results showed that immobilized introduced bacteria, either single or mixed, had higher degradation efficiency than dissociated bacteria. Compared with indigenous bacteria, some introduced bacteria had predominance to some degree. The introduced bacteria-mixture had better degradation efficiency after being immobilized. The degradation rate of pyrene and benzo(alpha) pyrene after treated with immobilized bacteria-( B61-B67) mixture for 96 hours was 43.49% and 38.55%, respectively. PMID- 17269359 TI - [Differences between guidelines on management of COPD]. PMID- 17269360 TI - [The frequency of allergy in lung cancer patients]. AB - Lung cancer is the most common malignancy in the world and frequency of allergic diseases increases especially in high-developed countries. In the literature there have been published articles about association between lung cancer and allergic diseases, which don't give a simple answer if there is any connection between them. The aim of this study was the assessment of frequency of allergy in patients with lung cancer. The study was based on medical records and questionnaire performed among patients hospitalized in Department of Pneumonology and Allergology Medical University of Warsaw and in Department of Thoracic Surgery Institute of Tuberculosis in Warsaw. The study included 113 patients (30 women and 83 men). Coexistence of allergy with primary lung cancer was observed in 7 cases which makes 6.2% (frequency of: asthma 1.8%, allergy to drugs 3.5%, allergy to animal's dander 0.9%). The result of this examination reveals that there is significant lower frequency of allergic diseases in patients with lung cancer in comparison with frequency of allergic diseases in adult population of Poland estimated at 15.8%. PMID- 17269361 TI - [The epidemiology of tuberculosis of the respiratory tract in the homeless in Poznan]. AB - The Department of Health and Social Care of the Municipal Council in Poznan initiated a programme of prophylaxis against tuberculosis in the homeless. The study involves those homeless people who are registered in Poznan-based homeless shelters and temporary residential sites. Chest x-ray was performed in 403 homeless and 57 persons of staff. Abnormal picture of the chest was found in 83 person, but only in 30 lesions were suspected of tuberculous etiology. 43 persons with abnormal chest x-ray and/or with clinical symptoms were exactly examinated in Chest Clinic (with microbiological examination of sputum or bronchoscopic material). AFB were found in 7 of them, in 1-granulomatosis with necrosis was found in lung specimen and in 2 clinical and radiological diagnosis of TB was estabilished. PMID- 17269362 TI - [Safety of venom immunotherapy in patients pretreated with antihistamines--a retrospective study]. AB - Immunotherapy is the only effective method of treatment of allergy to Hymenoptera venom. Pretreatment with antihistamines diminishes the incidence of adverse reactions (AR) such as large local and mild systemic reactions but it is suggested that it may mask a development of serious allergic reactions. The aim of the study was a retrospective evaluation of the incidence and nature of AR during venom immunotherapy in patients receiving pretreatment with antihistamines in the Department of Pneumonology and Allergy of the Medical University of Lodz. RESULTS: 50 patients started "ultra-rush" immunotherapy in our center, 8 were taken in our care after the initiation phase had been conducted elsewhere. During the dose increase phase 10 systemic adverse reactions were observed. 50% of them were only subjective and the rest mild objective reactions. During the maintenance phase 10 systemic reactions were noted, among them 2 cases of the anaphylactic shock. The incidence of systemic adverse reactions was 1 per 86 injections. Late as well as unusual reactions appeared twice. CONCLUSIONS: Venom immunotherapy combined with pretreatment with antihistamines is safe. A vast majority of systemic adverse reactions is of subjective and mild objective nature and appropriate treatment leads to containment of severe reactions. PMID- 17269363 TI - [Hyperuricaemia in females with obstructive sleep apnoea]. AB - The aim of our study was to assess serum uric acid (UA) in a large group of females with OSA before treatment (normal UA value is from 2.4 to 5.7 mg/dL). We studied 105 consecutive females (73,3% without estrogen activity), mean age 58.5+/-9.9 years, mean BMI = 33.3+/-8.2 kg/m(2) with OSA (mean AHI = 35.6+/-21.5, mean overnight SaO2=89+/-6.3%). We divided patients in two groups: 1st with hyperuricaemia - UA>5.7mg/dL (53pts, 50.5%) and 2nd with normouricaemia - UA < 5.7mg/dL (52pts, 49.5%). Concentartion of serum uric acid was similar in females with and without estrogen activity. Subjects with hyperuricaemia had significantly higher BMI (p<0,001), lower mean SaO2 (p<0,01) and spent more time in desaturation below 90% (p<0,01). This group had lower FVC, FEV1 i PaO2 (p < 0,001), higher PaCO2 (p <0,01) and morning glucose (p <0,001). Females with OSA and hyperuricaemia presented higher prevalence of systemic hypertension (p < 0,001), coronary artery disease (p < 0,05), diabetes (not significant) and COPD (p < 0,05). Multiple regression analysis revealed relation between serum uric acid, BMI and arterial hypertension. CONCLUSIONS: Hyperuricaemia is frequent in females with OSA. Increased UA levels were related especially to obesity and arterial hypertension. Lower: overnight SaO2, FVC, FEV1, PaO2 and higher glucose concentration and PaCO2 may play role in developing of hyperuricaemia. PMID- 17269364 TI - [Significance of virological diagnostics for the effective treatment of hospitalized patients infected with influenza virus]. AB - In the case of influenza disease there is no possible to make unquestionable diagnosis only on the basis of clinical picture. Therefore, virological laboratory diagnostics is important, especially in hospitalized patients and those who highly risk post-influenza complications and severe course of the disease. Virological diagnostic tests for influenza and positive result obtained in these tests allow to use effective antiviral-antiinfluenza drugs as new generation drugs: oseltamivir and zanamivir and also old generation drugs: amantadine and rimantadine. Since these antivirals are effective only in the case of influenza infection, diagnostic tests should be performed previously. Present methods allow to obtain the result of the test within less than 1 hour to 8 hours. This is of great importance, because the administration of the drug within 36 hours from the onset of symptoms is one of the factors conditioning the effectiveness of antiviral therapy. In the present paper there are described four cases of hospitalized patients in whom the infection with influenza virus was confirmed by immunofluorescence test and RT-PCR, and then the antiviral antiinfluenza drugs were immediately introduced. This antiviral therapy in a short time resulted in the improvement of patients' condition and allowed to discharge them from the hospital. Antiviral-antiinfluenza drugs together with virological diagnostics are the effective tool in the case of patients not vaccinated against influenza, who were infected with influenza virus and fell ill. PMID- 17269365 TI - [Analysis of the treatment (neoadjuvant chemotherapy and surgery) in IIb and IIIa stages of non-small cell lung cancer]. AB - THE AIMS: 1) comparison of NSCLC stages according to bronchoscopic and radiological findings with pathological outcome (mediastinoscopy), 2) efficacy of the neoadjuvant ChT by means of nodal involvement and primary tumour (downstaging), 3) influence of ChT on the surgical procedures' extension and its morbidity MATERIAL AND METHODS: 100 consecutive patients with resectable NSCLC in stages IIB (13 pts) or IIIA (57 pts), who were qualified to neoadjuvant ChT, participated in this study (77 men and 23 women, aged 42-73). Tumour and lymph nodes (mediastinal and hilar) were measured in CT scan. Mediastinoscopy was performed in 70 pts (70%). Majority of patients (87%) received two cycles of neoadjuvant ChT (cisplatin 80 mg/m(2) iv on day 1 and vinorelbine 25 mg/m(2) on day 1 and 5) administered every 21 days. After ChT 85 patients were qualified to surgery. THE RESULTS: The metastases in mediastinoscopy were excluded in 32 out of 45 patients (71%), whose lymph nodes were enlarged in CT scan (radiological false positive). Metastases were confirmed in 4 out of 25 patients (16%), whose lymph nodes were normal in CT scan (radiological false negative). After ChT the regression of the disease (PR+CR) was noted in 37% of patients. Pneumonectomy was performed in 23 (27%) pts, bilobectomy in 11 (13%) pts, lobectomy in 39 (46%) pts and "extended" (sleeve) lobectomy in 12 (14%) pts. Resected material was examined microscopically very exactly in patients, in whom mediastinoscopy was performed before treatment. Down-staging was confirmed in 6 out of 15 patients (40%). CONCLUSIONS: Neoadjuvant ChT was effective in 37% of patients and allowed us to perform less extensive surgery in these patients. 22 (64,7%) out of 34 patients who responded to ChT underwent lobectomy. Only 17 (36%) out of 51 patients who did not respond to ChT had lobectomy performed. Generally, 85 pts were operated with postroperative complications in 22.3% patients and 2.3% mortality rate. Pneumonol. Alergol. Pol. 2006, 74, 171:178 PMID- 17269366 TI - [Epidemiological situation concerning lung cancer in Wielkopolska in 1975-2002]. AB - Lung cancer is the main cause of cancer deaths around the world. At 12% of all cancer incidents, lung cancer is the most frequent single cause of death, of both males and females. In 2002 among male population in Poland, lung cancer was the second, following heart failure, cause of death, ranging at 8% of deaths in general. It was third cause of death among females ranging at 2.3% in general. Considering cancer deaths in 2002 in Wielkopolska, lung cancer was most frequent cause of death among males (30%) and second frequent among females (10.4%). The last 25 years the number of deaths decreased among younger generation of males (first in the age group 20-44, later in the middle age group) and this phenomenon has dominated the general picture of cancer among males. However the increase of mortality rates in the older age group might be still observed. The constant increase of mortality has been observed among females, especially in the middle age group (45-64). It should be highlighted that the level of mortality has been equalled in both genders in the youngest age group (20-44), which means suddenly growing risk among young population of women in Wielkopolska. PMID- 17269367 TI - [VEGF in the cancer anorexia-cachexia syndrome in patients with lung cancer]. AB - Cancer anorexia-cachexia syndrome( CACS) occurs in 30-80% of patients with cancer. CACS is connected with poor prognosis and higher risk of treatment complications. CACS belongs to the common cause of death in cancer patients. Main role in the development of this syndrome play cytokines like TNF, interleukin 1 and 6 and interferon alpha and gamma. The importance of a lot of other substances is still unknown. VEGF promotes new vessels development,enhance vascular permeability and plays a role in inflammatory reaction. The aim of this study was comparison of VEGF levels in patients with lung cancer with and without CACS and in control group. The serum levels of VEGF were measured by ELISA method. The VEGF was significatly higher in patients with lung cancer then in control group (p = 0.004). There were no correlations between VEGF and weight lost, histological type and stage of disease. This suggest that VEGF doesnt play a role in development of CACS. PMID- 17269368 TI - [Increased levels of RANTES in induced sputum of chronic asthma but not in seasonal grass pollen-induced rhinitis]. AB - BACKGROUND: [corrected] Allergic rhinitis is one of risk factors for development of allergic asthma. METHODS: 9 patients with asthma, 16 patients with seasonal allergic rhinitis (SAR) due to grass or rye pollen sensitization and 17 healthy control subjects were recruited to the study. SAR patients were identified by history, skinprick test, specific IgE and positive nasal allergen challenge. Every subject underwent the methacholine bronchial provocation test and sputum induction. Levels of RANTES were measured in supernatant of induced sputum. RESULTS: Increased percentage of eosinophils in induced sputum in asthma compared to control group (p=0.01) but not in SAR patients compared to healthy subjects (p=0.13) were found. Similarly, asthmatic patients (p=0.01) but not SAR patients had increased levels of RANTES in sputum compared to healthy subjects. CONCLUSION: Increased levels of RANTES in induced sputum of patients with chronic asthma but not in SAR patients indicate that RANTES is important in pathogenesis of chronic airway inflammation. PMID- 17269369 TI - [Invasive aspergillosis (IA) in patients treated in the Institute of Tuberculosis and Chest Diseases in the years 1993-2005--diagnostic problems]. AB - The aim of this study was to present the diagnostic problems in pts treated for invasive aspergillosis (IA) in the IIIrd Clinic of the Institute of Tuberculosis in the years 1993-2005. The material consisted of clinical documentation of 18 pts. 15 out of 18 pts (83,4%) died. In all those cases autopsy examination was done. In 13 pts IA was the main and in another 2 only the accessory cause of death. All pts were treated with corticosteroids and/or cytostatic drugs because of lung cancer (13 pts), haematologic disorders (1 pts), Wegener's granulomatosis (3 pts) and idiopathic pulmonary fibrosis (1 pts). In 13 out of 18 pts granulocytopenia was revealed (on an average from 0,008 x 10(9)/L to 0,95 x 10(9)/L) one month before death. In 13 pts IA was limited to the lungs, in 5 others there were also fungal lesions in brain, kidneys, liver, spleen, pleura, pericardium and heart. Pts with disseminated form of IA had significantly lower granulocyte count and were treated with higher doses of corticosteroids than others. Immunosupressive drugs and granulocytopenia can be regarded as predisposing factors. IA was diagnosed before death only in 5 out of 18 pts. This was mainly caused by the lack of the symptoms of infection (4 pts) and negative results of mycological (6 pts) and serological examination (8 pts). We should underline that mycological examination was only done in 11 pts and serological examination of blood for fungal antigen only in 6 pts. We conclude that mycological infection ought to be searched in all pts treated with high doses of corticosteroids and those with prolonged granulocytopenia, especially if they have the symptoms of infection which does not respond to antibiotic therapy. PMID- 17269370 TI - [Humoral immune response against mycobacterial antigens in patients with tuberculosis and mycobacterial infections other than tuberculosis]. AB - The aim of the study was to compare humoral immune response against various mycobacterial antigens in TB and MOTT vs healthy control group. 350 serum samples from TB patients, 20 samples from MOTT patients and 58 samples from healthy donors were examined. ELISA detecting IgG, IgA and IgM against antigens: 38 kDa and 16 kDa, 38kDa and lipoarabinomannan, and A-60 were used. Mean IgG level was higher in TB compared to healthy controls (p<0,001). Mean IgG level against 38kDa and 38 + 16 kDa mycobacterial antigens was higher in TB than in MOTT group. Mean level of the IgG, IgA and IgM antibodies against LAM was higher in MOTT compared to TB patients. In all subgroups person-to-person heterogeneity of antigen recognition was observed. Humoral immune response to recombinant mycobacterial antigens significantly differs in TB and MOTT patients. PMID- 17269371 TI - [Chylothorax in patients with diffuse pulmonary lymphangiomatosis]. AB - The occurence of chylothorax is uncommon and usually is caused by trauma or neoplastic process of the mediastinum. Primary lymphatic lesions of the lungs are extremly rare. One of them is lymphangiomatosis --diffuse lesions characterized primarily by an increased number of complex anastomosing lymphatic channels in which dilatation is secondary phenomenon. These lesions can involve lungs, mediastinum and pleura. The prognosis for the patients with this disease limited to the thorax is guarded and progressive although some patients have realtively indolent course. We present 2 patients : 18-years old boy and 17-years old girl. admitted to hospital because of chylothorax. The diagnostic did could not allow to discover disruption of thoracic duct, even during thoracoscopy. In material taken from the pleura and mediastinum during exploratory thoracotomy - diffuse pulmonary lymphangiomatosis was found. CT examination of the chest revealed osteolysis of the spine. The girl died after 6 weeks from the first symptoms and boy is observed for 18 months with symptoms of progressive restrictive lung disease. PMID- 17269372 TI - [Thrombocytopenia probably heparin-induced in women with tumor of the heart and pulmonary embolism]. AB - 43 years old women with tumor of the right ventricle was admitted to ICU due to pulmonary embolism and suspicion for heparin-induced thrombocytopenia. Thrombocytopenia was successfully treated with Arixtra and the patient was qualified for the cardio surgery intervention. Heparin is widely used in treatment and prophylaxis of venous thromboembolism and other diseases. One of the most important adverse effect of treatment with heparin is heparin-inducted thrombocytopenia (HIT), which is one of the most frequent drug-induced, immune mediated type of thrombocytopenia. If it is unrecognized is associated with significant morbidity and mortality. According to our knowledge this is first report of Arixtra usage in patient with suspicion of HIT in Poland. PMID- 17269374 TI - [Pulmonary complications in patient with ulcerative colitis, treated with 5 aminosalicylic preparations]. AB - Pulmonary complications in patients with ulcerative colitis treated with 5 aminosalicylic acid are infrequent adverse events. The authors present a 35-year old man, taking sulfasalazine and mesalazine in whom pulmonary abnormalities resembling tuberculosis were observed during several months of therapy. Withdrawal of mesalazine resulted in complete resolution of lung injury. Patient is doing well on maintenance treatment with immunosuppressants PMID- 17269373 TI - [Latent tetany masked by syndroms of bronchial asthma and depressive syndrome. Case report]. AB - Tetany, which occurs in young women, poses common diagnostic problem. Two types of tetany are distinguished: one which is characterized by hypocalcemia and which rarely occurs (in person after strumectomy in the course of post-operational hypoparathyroidism) and latent one, which occurs more often. In the literature there is a lack of precise data concerned witch most probably results from its underestimation. Clinical symptoms which appear in latent tetany (normocalcemic) are related to the intracellular magnesium deficiency and increased respiratory drive. A noncharacteristic clinical picture and the lack of a pathognomonic symptom, cause that despite of the fearly common occurrence, the latent tetany is rarely recognized. In this paper the case of a 53 year old women has been described. The women had the symptoms of gastroesophageal reflux of asthma and depressive syndrome, witch masked the symptoms of the latent tetany. PMID- 17269375 TI - [Bacteria of the genus Acinetobacter: clinical significance and therapy of infections]. PMID- 17269376 TI - [The induced sputum--methodology and clinical usefulness]. PMID- 17269377 TI - [The importance of eosinophil cationic protein in pathogenesis of allergic diseases]. PMID- 17269378 TI - [Using flow cytometry in laboratory diagnosis of allergic diseases]. PMID- 17269379 TI - [Upper airway resistance syndrome]. PMID- 17269380 TI - [Lung transplantation: the scope of donor selection]. PMID- 17269381 TI - [Diagnosis and treatment of primary peptic stricture of the esophagus]. AB - Results of treatment of 271 patients, suffering primary peptic stricture of the esophagus (PPSE), were analyzed. Application of antireflux operation on esophagogastic junction with forceful esophageal bougienage had permitted to achieve recovery in majority of them. Esophageal resection is indicated in PPSE, which do not submit instrumental dilatation and in presence of high-grade dysplasia, situated within the organ segments, affected by metaplasia. PMID- 17269382 TI - [Prognosis of disability after performance of operation for complicated gastroduodenal ulcer]. AB - Quality of life of a patient constitutes integrated index of the treatment efficacy. One of parts of the "quality of life" term is a restriction of vital activities - disability. It is for the first time, when the prognostication system was proposed for the risk estimation of disability occurrence in patients, operated on for complicated gastroduodenal ulcer, which was elaborated on background of the step by step discriminant analysis. Application of prognostication system, in particular, its simplified variant, permits to apply it widely for choosing of optimal operative treatment method, which prophylaxes the risk of disability occurrence. PMID- 17269384 TI - [The small intestine intubation in the acute diseases of the abdominal cavity organs]. AB - The prolonged small intestine intubation is one of the main methods of pathogenetic therapy of acute diseases of the gut, complicated by persistent and prolonged inhibition of its motor function. Securing the gut decompression, she promotes elimination of microcirculation disorders in it, as well as its morphological and functional restoration, permits to evacuate toxic content, provides enterosorption, dialysis and other treatment measures, stops the intraabdominal hypertension syndrome occurrence. Open small intestine intubation via appendico- or cecostomy aperture constitutes one of the methods of its performance. The variant of small intestine intubation performance proposed, using original conductor, makes the procedure more technically simple, permitting to escape complications. There was adduced the analysis of conduction of small intestine intubation in 51 patients. PMID- 17269383 TI - [Anemia in patients with resectable tumour of periampullar zone organs as a risk factor of postoperative complications occurrence and its complex correction]. AB - Results of treatment of 39 patients, to whom pancreatoduodenal resection was performed for periampullar zone tumour, were analyzed. Anemia, revealed before the operation, had constituted the factor, which trustworthily increased the postoperative complications occurrence risk. Therapeutic course, using recombinant erythropoietins, was conducted for correction of anemia in 7 patients. This had promoted the hemoglobin level raising, the risk of postoperative complications occurrence lowering, but did not influence the intraoperative blood loss severity and perioperative hemotransfusion volume. PMID- 17269385 TI - [The immune aspects in the treatment of purulent-destructive affection of small intestine]. AB - Some indices of immune system were analyzed in 105 patients, suffering different kinds of purulent-destructive affection of small intestine. There was established that in such pathology the organism multifunction disorders occur, including that of the immune system. In such situation the disorders severity depends directly on the disease duration. Formation of the organism autoimmune reaction constitutes the end point of the process. The authors suggest that all the patients, in whom the early operation performance is impossible and conservative therapy is ineffective, the correction of the immune system disorders is indicated. PMID- 17269386 TI - [Hepatic sequestration]. AB - Various variants of hepatic resection, in 47 (94%)--atypical one and in 3- anatomic, was performed in 50 patients for surgical diseases of the liver. Hepatic sequestration was noted in 19 patients in early postoperative period, 11 of them died. Ultrasonographic investigation owes leading significance in early diagnosis of hepatic sequestration and in estimation of endogenic intoxication severity. PMID- 17269387 TI - [Morphological peculiarities of an acute pancreatitis]. AB - Results of morphological investigation of material, obtained while operation performance for an acute necrotic pancreatitis and autopsy, were presented. Histological peculiarities and pancreatic restoration processes in an acute necrotic pancreatitis were determined. PMID- 17269388 TI - [Rehabilitation and the quality of life estimation in patients suffering postoperative abdominal hernia before and after performance of reconstructive operation]. AB - The modern approach to rehabilitation and the quality of life securing in patients suffering postoperative abdominal hernia was elucidation. Using the rehabilitation algorrhythm elaborated in 69 (88.5%) patients suffering extent and giant hernia, satisfactory result was achieved after reconstructive operation performance, which had guaranteed the sufficient quality of life level. Poor result was noted in 9 (11.5%) patients, of them in 4 (5.1%) the disease recurrence had occurred, 5 (6.4%) were directed to expert medico-social commission. In these patients the quality of life indices did not differ from their values, presenting before the operation. PMID- 17269389 TI - [Prophylaxis of thromboembolic complications in patients, operated on for alimentary-constitutional obesity]. AB - Results of laparoscopic and open bariatric opeartions, made in 2 3 patients for alimentary-constitutional obesity (ACO) were analyzed. Restrictive gastroshunting was applied in 19 patients, biliopancreatic shunting according to N. Scopinaro method--in 4, gastric banding using special gastric rings--in 220. Practically in all the patients the consistent leaning was achieved. The efficacy of nonfractionized heparin and low-molecular heparin (Fraxiparine) application for prophylaxis of thromboembolic complications (THEC) was studied up in operated patients. According to our data obtained, in the group, consisting of 118 patients, in whom heparin was applied for the THEC prophylaxis, the rate of specific complications occurrence was in 7 times higher than in group of 113 patients, in whom Fraxiparine was applied for the THEC prophylaxis. While performing reoperations in patients, to whom Fraxiparine was administered in primary operation conduction for prophylaxis, the lower rate of adhesions in abdominal cavity or its absence was noted, comparing with such in group of patients, to whom Fraxiparine during first operation was not administered. Our experience witnesses that application of Fraxiparine during performance of bariatric operative interventions constitutes obligatory condition of successful management of patients suffering ACO in postoperative period, secures essential lowering of the THEC occurrence risk and reduces the adhesions formation in abdominal cavity. PMID- 17269390 TI - [Correspondence of intraabdominal pressure programmed by CO2 insufflator to pressure measured in bladder and stomach during laparoscopic operation]. AB - There are presented the results of intraabdominal pressure measuring in 75 patients, to whom elective laparoscopic cholecystectomy was performed. Intraabdominal pressure was measured using direct and indirect methods in bladder and stomach. The results of measuring, using direct and indirect methods, are similar. PMID- 17269391 TI - [Antiemetic effect of osetron used during endovascular operations in patients with vascular pathology of brain]. AB - The data concerning Osetron application for prevention and elimination of emesis and vomiting in postoperative period in patients with an acute disorder of the brain blood circulation according to hemorrhagic, ischemic and mixed types were presented. PMID- 17269392 TI - [Diagnosis and surgical treatment of false aneurism of proximal anastomosis after performance of aorto-femoral reconstruction for Leriche syndrome]. AB - In the clinic there were examined and treated 7 patients, ageing 38-69 years, suffering false aneurism of proximal anastomosis, which occurred after performance of aorto-femoral reconstruction for Leriche syndrome. Besides clinical data, ultrasonographic investigation of aorta was of principal meaning in diagnosis. All the patients were operated on: 2--for an urgent indications because of the prosthesis suppuration and arrosive hemorrhage occurrence and 5- in elective order. The volume of operation have depended on the patient general state, the aneurism etiology, its size and interrelationship with neighboring organs. The aneurism resection with formation of anastomosis and the blood flow restoration have constituted the main kind of operation performed in elective patients. Six patients had recovered and 1 died. PMID- 17269393 TI - [Classification of arterial reocclusion of the femoro-popliteo-tibial segment for the choice of the reconstruction method]. AB - The literature data, concerning the issues of terminology and classification of occlusion and reocclusion of the femoro-popliteo-tibial segment arteries were analyzed. Basing on analysis of the results of clinico-instrumental investigations performed, classification of the femoro-popliteo-tibial segment arteries reocclusion was proposed, which it is expedient to apply while making choice of the rereconstruction method. PMID- 17269394 TI - [The method of lifting and fixation of superficial musculo-aponeurotical system in rejuvenation operations on the face]. AB - The method of neck-facial facelifting, consisting of restrited dissection of adiposo-cutaneous flap and fascial sheet of superficial musculo-aponeurotical system (SMAS), its suturing using multiple quilts in a closed loop fashion, lifting of the neck-facial tissues en bloc along vertical vector. The thread is conducted subperiosteal in zygomatic arch region, securing safe fixation of the SMAS flap, permits to achieve harmony and to make the rejuvenation effect more durable. PMID- 17269395 TI - [Estimation of possibilities of conventional and nontraditional methods of diagnosis of the thyroid gland diseases]. AB - There were analyzed 445 hospital history charts of patients, who were operated on for the thyroid gland pathology. The trustworthiness of complex of conventional and nontraditional methods of treatment was estimated. The plasma of 100 patients with diseases of thyroid gland was investigated, using laser correlation spectroscopy. In 228 patients the titer of autoantibodies to normal tissue of thyroid gland in the blood serum was determined. Application of laser correlation spectroscopy and determination of the autoantibodies titer to normal tissue of thyroid gland have permitted to obtain additional information, permitting to improve the quality of diagnosis and differential diagnosis of the thyroid gland diseases. These methods are recommended to be included in complex of the screening investigations. PMID- 17269396 TI - [Biocomposit--a new material for the bone restoration]. AB - The results of application in 15 patients of a new implantation material biocomposit for the bone defects substitution, which constituted the consequences of the giant-cell tumor extirpation, are adduced. In all the patients the restoration of the extremity function and supportive ability have been succeeded. PMID- 17269397 TI - [Surgical treatment of patients suffering esophageal cancer and stomach cancer spreading to the esophagus using abdominocervical access]. AB - Radical operative interventions using abdominocervical access were performed in 145 patients for esophageal and gastroesophageal cancer. Of them in 99 (68.3%) patients isoperistaltic esophagoplasty was performed: in 54 (54.5%)--using isoperistaltic tube, formatted from gastric big curvature, in 23 (23.2%)--portion of jejunum, in 18 (18.2%)--portion of colon and in 4 (4.1%)--ileocecal angle. Retrosternal way of transplant transposition toward the neck was choused in 86 (86.9%) patients, via the resected esophagus bed--in 10 (10.1%) and subcutaneous one, presternal--in 3 (3%). Postoperative mortality had constituted 10.3%. For locally advanced cancer, affecting thoracic esophagus or gastroesophageal one the performance of subtotal-total esophageal resection is indicated. Application of abdominocervical access owes essential advantages for the patient and surgeon, comparing with lateral thoracotomy, because it secures less traumatic, adequately wide and visually controlled approach to mediastinal structures in esophageal cancer, and is characterized by oncological loyalty and surgical utility. PMID- 17269398 TI - [Role of antisecretory therapy in prophylaxis and treatment of postoperative stress ulcers of the digestive tract in patients with malignant tumors using preparation omez]. AB - The prophylaxis and treatment methods of the gut stress ulcers and gastrointestinal bleeding in early postoperative period in patients suffering malignant tumors of abdominal cavity organs were presented. High efficacy of proton pump inhibitor Omez in the injection form was noted for prophylaxis of the gut stress ulcers and gastrointestinal bleeding in early postoperative period. There was shown, that Omez constitutes one of the main components of complex antisecretory therapy of the gut stress ulcers and gastrointestinal bleeding in persons, operated on for oncologic disease. PMID- 17269399 TI - [Diagnosis and treatment of esophageal leyomyoma]. AB - Radical operations for benign esophageal leyomyoma were performed in 50 patients in 1976-2006 in the clinic. Highly informative roentgenologic, endoscopic and ultrasonographic (including intraesophageal) methods were applied in the disease diagnosis, permitting to establish the diagnosis, as a rule, accurately before the operation. The diagnosis was verified definitely, basing on intraoperative revision data and the results of express-histologic investigation of the tumor excised. Extramucosal enucleation of benign leyomyoma with plastic closure of esophageal muscle defect or its suturing was done in 33 (66%) patients. Subtotal esophageal resection was performed in 11 (22%) patients, reconstructive operations--in 10 (20%), including in 5 (10%)--retrosternal esophagocolonoplasty, in 2 (4%)--intrathoracic esophagogastroplasty and in 1 (2%)--retrosternal esophagojejunoplasty. In 2 (4%) patients with small benign leyomyoma the esophageal wall portion resection was performed using suturing apparatus and in 1 (2%)--gastrostomy. Postoperative mortality had constituted 2%. Results of treatment were studied in 46 (92%) patients in 1-18 yrs, 4.8 at average. There were no recurrences. The result was estimated as good in 39 (78%) patients and fair--in 7 (14%). PMID- 17269400 TI - [Prognostic possibilities of immunogenetic markers application in adhesive disease of abdominal cavity]. AB - Modern knowledge concerning adhesive disease of abdominal cavity is imperfect, that's why it is necessary to discover new and effective methods of investigation of the disease to improve prophylactic and treatment measures. There was studied up the distribution of the HLA system antigens in adhesive disease, markers of predisposition to the disease occurrence were revealed. The HLA typing results in 52 patients of Georgian nationality, suffering adhesive disease of abdominal cavity, are presented. Trustworthy increase of frequency of the HLA antigens Al, B15, B21 revealing was noted in patients in comparison with such in control group. According to the relative risk criterion, maximal possibility of the adhesive illness occurrence was connected with HLA-B15 antigen. It may be concluded that in Georgian population antigen HLA-B15 constitutes a genetic marker of the adhesive illness occurrence. PMID- 17269401 TI - [Application of minilaparotomy approach in emergency surgery of an acute cholecystitis]. AB - Results of surgical treatment of 118 patients suffering an acute calculous cholecystitis, using vertical transrectal minilaparotomy approach in the right subcostal region, were analyzed. In 106 (89.8%) patients concomitant diseases were diagnosed, an 95 (89.6%) of them--the concurrent ones. The hospital stay had constituted 4-8 days. All the patients had recovered. PMID- 17269402 TI - [Intraoperative monitoring of the bile ducts using transillumination as the method of iatrogenic damage prophylaxis and choledocholithiasis diagnosis]. AB - The necessity of application of intraoperative transillumination while performing operations on hepatoduodenal zone was studied up, basing on analysis of treatment results of 35 patients. Application of the method made it possible to diagnose choledocholithiasis in 16 patients, to verify tubular-luminal structures of hepatoduodenal ligament and to escape their iatrogenic damage in infiltrative adhesional conditions--in 19. PMID- 17269403 TI - [Pathogenesis and treatment of hemocoagulation disorders in an acute necrotic pancreatitis]. AB - Results of investigation of content of activated protein C, Intercellular Adhesion Molecule -1 (ICAM-1) and interleukin (IL)--18 in the patients with an acute pancreatitis were presented. At the hospital attendance the concentration of IL-18, ICAM-1 increase and the activated protein C level lowering were noted. The strict immediate correlation connection between serum blood level of IL-18, ICAM-1 and hematocrit and the reverse one--between these mediators concentration and the activated protein C content--were noted during all period of observation. PMID- 17269404 TI - [Effect of preoperative care on intraabdominal and perfusion pressure in the abdominal cavity]. AB - Data of measurement of intraabdominal pressure (IAP) and perfusion pressure in abdominal cavity (PPAC) in patients, to whom abdominal wall plasty, using synthetic net, was performed, including 42--without preoperative preparation (1st group) and 51 (2nd group)--after performance of preoperative preparation, applying combined anesthesia with artificial ventilation of lungs. In the patients of second group IAP after the operation was lower and PPAC--higher, in comparison with these indices in the first group. PMID- 17269405 TI - [Organoprotectivity--criterion of adequacy of anesthesia in microsurgery]. AB - Intravenous narcosis was applied while performing surgical correction of consequences of traumatic damage of tissues using microsurgical technique. The targeted value of systolic arterial pressure, organoprotective delivery and organoprotective consumption of oxygen were used as criterions of the anesthesia adequacy. PMID- 17269406 TI - [The choice of operative method for the arterial occlusion in the femoro-popliteo tibial segment]. AB - The results of surgical treatment of 198 patients suffering atherosclerotic occlusion of the femoro-popliteo-tibial segment arteries were analyzed, of them endarterectomy from superficial femoral artery was performed in 75 (37.9%) patients, femoro-popliteal shunting using autovena--in 93 (47%), synthetic prosthesis--in 17 (8.6%), in 4 (2%)--distal anastomosis was formatted with "hanged" segment of popliteal artery, revascularization of the limb via the deep femoral artery system was done in 9 (4.5%) patients. Good immediate result was noted in 86.4% patients, in 2 years and more--in 68.6%. Comparative analysis of methods of the femoro-popliteo-tibial segment arteries reconstruction had trusted, that more stable indices of hemodynamics were achieved after performance of autovenous shunting with formation of distal anastomosis via proximally than the knee joint fissure localisation. PMID- 17269407 TI - [Extrapleural thoracoplasty as an alternative to pulmonectomy]. AB - Basing on the literature data, negative tendency for the modern tuberculosis course was substantiated. The main causes of conservative treatment failures for chronic and aged forms of tuberculosis were shown. The data concerning the surgical treatment character change for pulmonary tuberculosis, from resection toward thoracoplasty, were adduced. The authors consider extrapleural thoracoplasty as an alternative to pulmonectomy. PMID- 17269408 TI - [Efficacy of intraoperative apparatus autotransfusion of the blood in revisional endoprosthesis of the hip joint]. AB - Significant blood loss and the methods of its compensation constitute one of the main problems of revisional prosthesis of big joints. Application of a patient's blood constitutes the most available and secure way of the problem solution at the modern stage of surgery evolution. The apparatus autotransfusion of the blood owes prominent place in the system of the blood saving, solely as well as in combination with autodonoring and preoperative hemodilution. In the patients, to whom the revisional prosthesis of the hip joint was performed, using intraoperative apparatus autotransfusion of the blood and the donor's erythrocytes, the red blood indexes were investigated on the stages of operative intervention and postoperative period. Application of apparatuses, such as Cell Saver, constitutes optimal and secure method of the blood oxygentransporting function restoration in the revisional prosthesis of big joints operations. PMID- 17269409 TI - [Clinico-roentgenological semiotics of the chest damage in polytrauma]. AB - There are presented the main clinico-roentgenological signs of the chest damage in the injured persons, suffering polytrauma, according to the data from the specialized department of traumatic shock and polytrauma. PMID- 17269410 TI - [Changes of duodenal biochemical content in the early duodenal recurrent hemorrhage]. AB - The dynamics of the indices changes concerning the general protein, urea and glucose content was investigated in 32 mongrel dogs while modelling the hemorrhage from duodenum and its early recurrence. There was established that the urea content and somewhat the general protein content reflect most accurately the hazard of the early recurrent hemorrhage occurrence. PMID- 17269411 TI - [Actuality of the vagus nerve preservation during esophagectomy for esophageal cancer]. PMID- 17269412 TI - [Observation of successful treatment of the spleen artery aneurism]. PMID- 17269413 TI - [Application of cava-filter for prophylaxis of the pulmonary artery thromboembolism]. PMID- 17269414 TI - [Acute gangrenous-perforative appendicitis simulating incarcerated inguinal hernia]. PMID- 17269415 TI - [Clinical and economic analysis of the management of patients with duodenal ulcer]. PMID- 17269416 TI - [Morphological features and secretory gastric function in patients with chronic gastritis against the background of B12 deficiency anemia]. AB - As many as 45 patients with chronic atrophic gastritis against the background of B12 and iron-deficiency anemia were examined. Chronic atrophic gastritis combined with B12 deficiency anemia was found to damage in most cases the antral and fundic parts of the stomach simultaneously, while the gastric process combined with iron-deficiency anemia involved the antral part only in most cases. The disease is accompanied by a considerable reduction of acid, pepsinogen and biermerin formation, especially in cases of chronic atrophic gastritis associated with B12 deficiency anemia. PMID- 17269417 TI - [State of the mouth cavity in patients with inflammatory intestinal diseases]. AB - The article presents the results of the dental examination of 75 patients with ulcerative colitis and Crohn's disease with mild and medium-to-severe clinical course. Absolutely all of the patients had intensive dental caries and inflammatory diseases of the paradontium that exceeded the average statistical level for Moscow both in terms of incidence and severity. As many as 20-60% of patients suffering from inflammatory intestinal diseases also had such disorders of the mouth cavity mucous membrane as angular cheilitis, labial fissures, glossitis or aphthous stomatitis. The reduction of the alveolar bony tissue was usually found in cases of gingivitis and paradontosis. It was demonstrated that the treatment of this type of pathologies as well as preventive measures can essentially reduce the mouth cavity disease incidence for this group of patients and improve their life quality. PMID- 17269418 TI - [Incidence of the gene cagA and amount of microbial bodies of Helicobacter pylori in biopsy materials--what is the correlation?]. AB - The study objective was to determine the correlation between the incidence of cagA gene of Helicobacter pylori (H. pylori) and the quantity of microbial bodies of H. pylori in biopsy materials of the gastric mucous coat. As many as 85 patients with duodenal ulcer (DU), 52 patients with gastric ulcer (GU), 41 patients with atrophic gastritis (AG) and 53 patients with post-resection syndrome (PRS) were examined. Statistically significant results revealed weak correlation in patients with AG and PRS and medium correlation for patients with DU and GU. Therefore, the count of microbial bodies of H. pylori in biopsy materials as the method for predicting the presence of cagA gene in H. pylori can be used only in cases when the gastric secretion is decreased, i.e. for patients with AG and PRS. PMID- 17269420 TI - [Order of the Russian Ministry of Health no. 330 as of August 5, 2003: on measures to improve dietotherapy in therapeutic institutions in the Russian Federation. Critical analysis by a practicing dietician]. PMID- 17269419 TI - [Helicobacter pylori and symptoms of gastroesophageal reflux in adolescents: role of cagA-comprising strains]. AB - The objective of this study was to assess the prevalence of gastroesophageal reflux symptoms (GERS) in 403 adolescents at the age of 14-17 according to the Helicobacter pylori status in a two-year prospective school-based survey. Initially the H. pylori infection was revealed in 55.3%. GERS were reported by 16.1% of H. pylori negative subjects, 17.3% of H. pylori positive but CagA negative adolescents, and by 30.3% of those being CagA positive. Over 2 years, among 275 subjects without initial GERS, symptoms appeared in 43 (15.6%), being 10.8%, 18.8%, and 21.0% in three groups under the study, respectively. The H. pylori infection (especially with CagA positive strains) in older children results in GERS, which can be explained by antral gastritis with a subsequent increase of acid secretion. PMID- 17269421 TI - [Clinical and laboratory criteria for assessing the efficacy of Essliver Forte for patients with combined liver and gall bladder pathologies]. AB - As many as 60 patients with combined pathologies (chronic hepatitis (CH) and chronic non-calculous cholecystitis (CNCC)) were examined, and 20 healthy subjects were included in the control group. The efficacy of Essliver Forte for patients with chronic non-calculous cholecystitis combined with chronic hepatitises (both viral hepatitis and steatohepatitis) was assessed on the basis of clinical, biochemical and bacteriological criteria. Essliver Forte was found to improve the clinical and biochemical parameters of the functional liver condition, bile biochemical characteristics and intestinal microbiocenosis in patients with combined pathologies. The positive clinical effect is most evident for patients with chronic non-calculous cholecystitis and chronic steatohepatitis (both alcohol and non-alcohol). Essliver Forte can be recommended for treatment of patients with combined pathologies. PMID- 17269422 TI - [Prevalence, risk factors and significance of clinical manifestations of cholelithiasis among the population of Moscow]. PMID- 17269423 TI - [Effect of the concomitant pathologies of the hepatobiliary system on the ulcer course and substantiation of the use of Essliver Forte as a part of the complex therapy]. PMID- 17269424 TI - [Safety of proton pump inhibitors for long-term application]. PMID- 17269425 TI - [New paradigm of the GERB and long-term therapy with proton pump inhibitors]. PMID- 17269426 TI - [Methods for increasing the efficacy and safety of Helicobacter pylori eradication regimens]. PMID- 17269427 TI - [Pharmacoeconomic aspects of the use of proton pump inhibitors]. PMID- 17269428 TI - [Case of intestinal adenocarcinoma]. AB - The article describes the clinical picture and particular features of the diagnostics of the neoplastic process with uncommon localization--intestinal adenocarcinoma. The authors present their own observations. PMID- 17269429 TI - [Metabolism of porphyrins in patients with hepatic cirrhosis]. AB - The article analyses the results of the study of porphyrins metabolism in 53 patients with chronic hepatic diffuse diseases at the stage of hepatic cirrhosis (HC). HC of viral etiology was diagnosed in 16 patients, and HC of ethanol etiology--in 9 patients. As many as 11 patients were diagnosed with primary biliary cirrhosis (PBC), and 10 patients--with idiopathic hemochromatosis (IHC). As many as 3 patients with manifested late skin porphyria developed secondary hemochromatosis, and 4 patients have manifested late skin porphyria with HC. Nonspecific disorders of porphyrins metabolism were revealed in 14 patients suffering from viral HC, 7 patients with ethanol HC, 9 ones with PBC and 8 suffering from IHC. Altogether 38 patients (82.6%) of the entire group of examined patients had pathological abnormalities. Porphyrins metabolism disorders manifested various combinations of biochemical features. Increased values of all porphyrin fractions in urine and faces were the most common characteristics (15 patients) as well as secondary coproporphyrinuria (15 patients). Symptoms of the growth of porphyrins in faces was less frequent (8 patients). Porphyrins metabolism disorders were assessed as a negative factor as the accumulation of the excessive amount of porphyrins in hepatocytes results in a rapid progress of hepatocellular deficiency. The dynamic assessment of porphyrins metabolism values is considered to be an important prognostic criterion for HC. The tested reduction of the porphyrin level can be a sign of hepatic deficiency with a serious prognosis. PMID- 17269430 TI - [Complex use of ultrasound tomography in the algorithm of diagnostics for patients with acute destructive pancreatitis]. AB - The article describes the experience of puncture aspiration biopsy in 136 patients (110 males and 26 females at the age of 19-74) with suspected destructive pancreatitis in one-day inpatient conditions, followed by microscopic and microbiological tests. In order to increase the diagnostic accuracy when detecting necrotic zones, 49 patients were examined by ultrasonic tomography using the color Doppler mapping and the method of energetic Doppler with subsequent spot puncture. The results of microbiological and cytological tests of the smear materials taken by fine-needle aspiration under ultrasonic control enable the authors to use the most efficient antibacterial therapy as well as to support the strategy of surgical treatment of destructive pancreatitis in its various forms in the conditions when clinical differential diagnosis is complicated. These methods increase the efficacy of medical treatment for this category of patients. PMID- 17269431 TI - [Particular features of the clinical manifestation, course and treatment effects of stomach and duodenal ulcers depending on the functional activity of ribosomal genes]. AB - The article presents a study of the functional activity of ribosomal genes in 134 patients with gastric and duodenal ulcer and 48 healthy subjects. A statistically significant reduction of this parameter for patients with peptic ulcer vs. the general population was shown. The authors demonstrated the relation between specific features of the peptic ulcer clinical picture, its progress, results of treatment of these disease entities and functional activity of ribosomal genes. The relation between the functional activity of ribosomal genes, ulcer localization and progress of ulcer complications was demonstrated. The results achieved suggest that the protein synthesis system is involved in all stages of peptic ulcer pathogenesis and sanogenesis. PMID- 17269432 TI - [Matvey Yakovlevich Mudrov (On the 175th anniversary of the death date]. PMID- 17269433 TI - Nursing professional development certification. PMID- 17269434 TI - Depression in the elderly. PMID- 17269435 TI - Leadership skills beyond the bedside: professional development classes for the staff nurse. AB - Preparation for advanced leadership roles requires hospital-based staff nurses to develop skills beyond clinical expertise. Non-clinical activities such as poster and oral presentations, article publication, and professional portfolio development are ways to demonstrate these skills. This article cle discusses how an educational initiative was developed to provide instruction and mentoring for these areas of professional development. In addition, the relationship between this initiative and a clinical advancement ladder is discussed. PMID- 17269436 TI - Learning to think like a nurse: stories from new nurse graduates. AB - One aim of nursing education is to help students learn to be beginning practitioners, which includes making clinical judgments that ensure patient safety. Clinical judgments often determine how quickly nurses detect a life threatening complication, how soon patients leave the hospital, or how quickly patients learn to take care of themselves. However, current research shows that new graduates do not perform well when making clinical judgments, despite having graduated from accredited schools of nursing and passing the NCLEX examination. This descriptive, qualitative study examined the perceptions of recent nursing graduates about learning to make clinical judgments. Graduates with baccalaureate degrees in nursing were interviewed three times in 9 months to determine their perceptions of how they learned to think like nurses. The results of this study should be useful in identifying strategies to help new graduates make the transition from students to registered nurses. PMID- 17269437 TI - Creating value-added linkages through creative programming: a partnership for nursing education. AB - Academic and clinical institutions can effectively collaborate to deliver programs that enhance the educational level of the nursing staff. Creative programming, which offers flexibility and convenience, and a reasonable cost are key elements in the success of a program. Open communication and mutual recognition and respect of the talents, abilities, and values of all developers of the program are essential factors in effective collaborations leading to successful partnerships. Although clear expectations and clarity of functions are important once the partnership has developed, flexibility and a desire to "own" both the problems and the successes of a program are crucial to success. PMID- 17269438 TI - Barriers to screening for domestic violence in the emergency department. AB - The identification of victims of domestic violence is important to prevent further abuse and injury. The purposes of this pilot project were to identify potential barriers emergency department registered nurses encounter in screening patients for domestic violence and to assess nurses' educational backgrounds for continuing education and training needs. The most significant potential barriers to screening identified were a lack of education and instruction on how to ask questions about abuse, language barriers between nurses and patients, a personal or family history of abuse, and time issues. These findings may benefit other researchers who are trying to determine the continuing education needs of emergency department staffs. PMID- 17269439 TI - Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. AB - Stem cell transplants into spinal cord lesions may help to improve regeneration and spinal cord function. Clinical studies are necessary for transferring preclinical findings from animal experiments to humans. We investigated the transplantation of unmanipulated autologous bone marrow in patients with transversal spinal cord injury (SCI) with respect to safety, therapeutic time window, implantation strategy, method of administration, and functional improvement. We report data from 20 patients with complete SCI who received transplants 10 to 467 days postinjury. The follow-up examinations were done at 3, 6, and 12 months after implantation by two independent neurologists using standard neurological classification of SCI, including the ASIA protocol, the Frankel score, the recording of motor and somatosensory evoked potentials, and MRI evaluation of lesion size. We compared intra-arterial (via catheterization of a. vertebralis) versus intravenous administration of all mononuclear cells in groups of acute (10-30 days post-SCI, n=7) and chronic patients (2-17 months postinjury, n=13). Improvement in motor and/or sensory functions was observed within 3 months in 5 of 6 patients with intra-arterial application, in 5 of 7 acute, and in 1 of 13 chronic patients. Our case study shows that the implantation of autologous bone marrow cells appears to be safe, as there have been no complications following implantation to date (11 patients followed up for more than 2 years), but longer follow-ups are required to determine that implantation is definitively safe. Also, we cannot yet confirm that the observed beneficial effects were due to the cell therapy. However, the outcomes following transplantation in acute patients, and in one chronic patient who was in stable condition for several months prior to cell implantation, are promising. It is evident that transplantation within a therapeutic window of 3-4 weeks following injury will play an important role in any type of stem cell SCI treatment. Trials involving a larger population of patients and different cell types are needed before further conclusions can be drawn. PMID- 17269440 TI - Transplantation of bioreactor-produced neural stem cells into the rodent brain. AB - The development of new cell replacement strategies using neural stem cells (NSC) may provide an alternative and unlimited cell source for clinical neural transplantation in neurodegenerative diseases such as Parkinson's and Huntington's disease. The clinical application of neural transplantation using NSC will therefore depend upon the availability of clinical grade NSC that are generated in unlimited quantities in a standardized manner. In order to investigate the utility of NSC in clinical neural transplantation, undifferentiated murine NSC were first expanded for an extended period of time in suspension bioreactors containing a serum-free medium. Following expansion in suspension bioreactors, NSC were still able to differentiate in vitro into both astrocytes and neurons after exposure to brain-derived neurotrophic factor (BDNF), suggesting that bioreactor expansion does not alter cell lineage potentiality. Undifferentiated bioreactor-expanded NSC were then transplanted into the rodent striatum. Immunohistochemical examination revealed undifferentiated bioreactor-expanded NSC survived transplantation for up to 8 weeks and expressed the astrocytic immunohistochemical marker glial fibrillary acidic protein (GFAP), suggesting that the host striatal environment influences NSC cell fate upon transplantation. Moreover, no tumor formation was observed within the graft site, indicating that NSC expanded in suspension bioreactors for an extended period of time are a safe source of tissue for transplantation. Future studies should focus on predifferentiating NSC towards specific neuronal phenotypes prior to transplantation in order to restore behavioral function in rodent models of neurodegenerative disease. PMID- 17269441 TI - Murine brain progenitor cells have the ability to differentiate into functional neurons and integrate into the CNS. AB - Although neural stem and progenitor cells have been shown to differentiate into neurons, few studies have examined the physiological properties of the differentiated neurons derived from stem cells. Here we show that mouse brain progenitor cells (mBPCs) differentiated in culture by removal of mitogenic factors or addition of BDNF or GDNF express neuronal-specific proteins including MAP-2 and synaptobrevin II. However, these cells demonstrate small voltage-gated Na+ currents and are not able to generate action potentials. When the mBPCs are cocultured with developing rat hippocampal neurons, the stem cells differentiate into neurons expressing MAP-2, develop large voltage-gated Na+ currents, and are able to generate action potentials. To investigate the influence of a mature CNS environment on survival, differentiation, migration, and morphological integration, mBPCs were transplanted into the spinal cord of adult mice. Undifferentiated cells transplanted into the spinal cord exhibited limited migration and expressed NG2, but did not differentiate to express MAP-2. Predifferentiated cells migrated to both gray and white matter with about 23% cells developing MAP-2 immunoreactivity after 8 weeks. These results suggest that both the environment and state of differentiation may dictate migration and the differentiation pathway of stem cells after transplantation. PMID- 17269442 TI - Immunologic consequences of multiple, high-dose administration of allogeneic mesenchymal stem cells to baboons. AB - Mesenchymal stem cells (MSCs) express low immunogenicity and demonstrate immunomodulatory properties in vitro that may safely allow their transplantation into unrelated immunocompetent recipients without the use of pharmacologic immunosuppression. To test this hypothesis, three groups of baboons (three animals per group) were injected as follows: group 1 animals were injected with vehicle; group 2 animals were injected IV with DiI-labeled MSCs (5 x 106 MSCs/kg body weight) followed 6 weeks later by IM injections of DiO-labeled MSCs (5 x 10(6) MSCs/kg) from the same donor; and group 3 animals were treated similarly as group 2 except that MSCs were derived from two different donors. Muscle biopsies, performed 4 weeks after the second injection of MSCs, showed persistence of DiO labeled MSCs in 50% of the recipients. Blood was drawn at intervals for evaluation of basic immune parameters (Con A mitogen responsiveness, PBMC phenotyping, immunoglobulin levels), and to determine T-cell and alloantibody responses to donor alloantigens. Host T-cell responses to donor alloantigens were decreased in the majority of recipients without suppressing the overall T-cell response to Con A, or affecting basic parameters of the immune system. All recipient baboons produced alloantibodies that reacted with donor PBMCs. Two of six animals produced alloantibodies that reacted with MSCs. We conclude that multiple administrations of high doses of allogeneic MSCs affected alloreactive immune responses without compromising the overall immune system of recipient baboons. The induction of host T-cell hyporesponsiveness to donor alloantigens may facilitate MSC survival. PMID- 17269443 TI - Human bone marrow mesenchymal stem cells seeded on modified collagen improved dermal regeneration in vivo. AB - In the correction of functional and aesthetic impairments, loss of soft connective tissue creates the need for adequate implant material. The reconstruction of defects resulting from radical excisions, trauma, or hereditary diseases has seen the use of combined grafts and flaps. With the aim of minimizing donor site morbidity, new methods have been evaluated. Because of a low rate of vascularization, with artificial dermal templates the take has only been poor. As shown in previous studies, improved angiogenetic potency and epidermal formation has been obtained in modified, cell-seeded collagen matrices. We have now investigated the suitability of adult bone marrow mesenchymal stem cells (hMSC) for soft tissue engineering. In this study, hMSC were isolated and expanded. Cells (10(6)) were seeded onto EDC cross-linked collagen sponges and implanted in 30 immunodeficient mice. Collagen sponges without cells were used as controls. The grafts were evaluated after 2 and 6 weeks. After explantation, macroscopic appearance, weights, and histology (scaffold degradation, cellularity, and invasion depth of the seeded cells) were all assessed. After 2 and 6 weeks in vivo, new vessels were found macroscopically on all cell-seeded collagen grafts. The control grafts appeared to be degraded with a lower rate of vessel ingrowth. In the experimental group, weight gain was significant after 2 and 6 weeks in vivo compared to the same grafts after 72 h in vitro, while weight increased only slightly in the control group. Histologically, populated scaffolds showed a high density of vascularization under a capsule. The control sponges showed single capillaries and a thicker capsule. Compared to the controls, cellularity (cells/field) was greater in cell-containing collagen grafts after 2 and 6 weeks. The results obtained demonstrate that in vitro cultured human mesenchymal stem cells seeded on modified collagen sponges may be able to act as a replacement for soft tissue. PMID- 17269444 TI - Establishment of cocultures of osteoblasts, Schwann cells, and neurons towards a tissue-engineered approach for orofacial reconstruction. AB - In orofacial reconstruction not only the osseous structures themselves but also neighboring cranial nerves need to be regenerated. To replace autologous bone implants, biocompatible tissue-engineered scaffolds are under investigation at least for bone replacement but until now these studies have not focused on parallel reconstruction of injured cranial nerves. The present study contributes to the development of optimized tissue-engineered products that will enable regeneration of both bone and nervous tissue. For the first time, cocultures of primary osteoblasts (rat or human) and primary Schwann cells (rat or human) were established. The suitability of monocultures of osteoblasts and cocultures of osteoblasts plus Schwann cells as substrate for sensory neurons as well as motoneurons was tested here. The results suggest that whereas osteoblasts provide a good substrate for sensory neurons, motoneurons depend on the presence of Schwann cells for survival and neurite outgrowth. For prolonged availability of regeneration-promoting growth factors at the site of the graft, those proteins should be delivered by the transplanted cells themselves. To enable this, we established electroporation-based nonviral transfection of osteoblasts as well as Schwann cells. Our new cell culture system will enable investigations of the effect of graft-derived growth factors on osteoblasts and Schwann cells as well as on neurite outgrowth from cocultured neurons of the sensory and motor system. PMID- 17269445 TI - The use of the BD oxygen biosensor system to assess isolated human islets of langerhans: oxygen consumption as a potential measure of islet potency. AB - The measurement of cellular oxygen consumption rate (OCR) is a potential tool for the assessment of metabolic potency of isolated islets of Langerhans prior to clinical transplantation. We used a commercially available 96-well plate fluoroprobe, the BD Oxygen Biosensor System (OBS), to estimate OCR in 27 human islet preparations, and compared these results to those of concurrent mouse transplantations. OCR was estimated both from the dO2 at steady state and from the transient rate of change of dO2 during the initial culture period immediately after seeding ("dO2 slope"). To demonstrate the validity of the OBS-derived values, it was shown that they scaled linearly with islet equivalent number/DNA concentration and with each other. These measurements were obtained for each preparation of islets incubated in media supplemented with either low (2.2 mM) or high (22 mM) glucose. Concurrently, one to three athymic nude mice were transplanted with 2,000 IEQs under the kidney capsule. The OCR Index, defined as the ratio of the DNA-normalized "dO2 slope" in high glucose to that in low glucose, proved highly predictive of mouse transplant results. Of the 69 mice transplanted, those receiving islets where the OCR Index exceeded 1.27 were 90% likely to reverse within 3 days, whereas those receiving islets with an OCR Index below 1.27 took significantly longer, often failing to reverse at all over a 35 day time period. These results suggest that the OBS could be a useful tool for the pretransplant assessment of islet cell potency. PMID- 17269446 TI - Adenovirus-mediated expression of the anticoagulant hirudin in human islets: a tool to make the islets biocompatible to blood. AB - Human islets induce an injurious clotting reaction at the time of transplantation. A potential strategy to counteract this reaction would be to allow the islets to express hirudin, a protein with direct anticoagulative activity. Human islets were transduced with an adenoviral vector encoding hirudin, an empty corresponding vector, or left untreated. Islet culture supernatants were analyzed for hirudin using an ELISA, a chromogenic substrate assay based on the thrombin-binding properties of hirudin and in a whole blood viscosimetry assay. Immunohistochemical evaluation and determination of hirudin content revealed an abundant expression of hirudin after transduction. Hirudin content in transduced islets was in the range of the insulin content levels. A delay in human whole blood clotting time could be observed after addition of supernatants taken from islet cultures expressing hirudin. However, transduced islets showed an impaired glucose-stimulated insulin release, but could readily be retrieved 6 weeks after transplantation to athymic mice. A marked expression and secretion of hirudin with functional capacity can be induced in human islets using an adenoviral vector. The impairment in glucose-stimulated insulin release in hirudin-secreting islets, compared to controls, indicates that the additional protein synthesis affects the functional capacity of the islets. PMID- 17269447 TI - Survival of an islet allograft deficient in iNOS after implantation into diabetic NOD mice. AB - Proinflammatory cytokines play a major role in rejection of pancreatic islet allografts and in type 1 diabetes (T1D). In rodent islets, exposure to IL-1beta alone or combined with IFN-gamma induces expression of inducible nitric oxide synthase (iNOS). Inhibition of iNOS or a deletion of the iNOS gene has been shown to be protective in animal models of T1D. In the present study we tested the hypothesis that transplantation of pancreatic islets deficient in iNOS (iNOS-/-) would permit increased graft survival. Pancreatic islets isolated from wild-type (wt) mice and iNOS-/- mice were allogeneically transplanted beneath the kidney capsule of spontaneously diabetic NOD mice. When blood glucose increased above 12.0 mM after preceding normalization of hyperglycemia, animals were sacrificed. Histological examinations of grafts were performed and graft gene expression was analyzed by real-time PCR. Transplantations of the two types of islets could reverse hyperglycemia and the grafts functioned for on average 1 week posttransplantation. Morphological examination of both types of islet grafts showed immune cell infiltration around and within the grafts. Remaining endocrine cells could be observed in wt and iNOS-/- islet grafts. In the removed grafts iNOS-/- islet tissue contained higher mRNA levels of insulin, proinsulin convertases (PC-1 and PC-2), and IL-1beta compared to transplanted wt islets. The assessments of insulin, PC-1 and PC-2 mRNAs of the grafts suggest that the iNOS-/ islets may be more resistant to destruction in the transplantation model used; however, this was not sufficient to prolong the period of normoglycemia posttransplantation. PMID- 17269448 TI - The effects of immunosuppressive agents on the function of human hepatocytes in vitro. AB - Calcineurin inhibitors (tacrolimus) and steroids continue to be an important component of hepatocyte transplantation protocols, despite reports of hepatotoxicity and inhibitory effects of steroids on cell proliferation. The aim of the study was to investigate whether isolated human hepatocytes were more vulnerable to the toxicity of these agents and also to investigate their effects on hepatocyte VEGF secretion, a vascular permeability factor suggested to be involved in the cell engraftment process. Human hepatocytes were isolated from donor livers/segments rejected or unused for orthotopic liver transplantation using a collagenase perfusion technique. Hepatocytes were plated for cell function tests and to determine VEGF production. Tacrolimus (0-50 ng/ml) and methylprednisolone (0-500 ng/ml) were added to the culture media and cells incubated for 24 h. Cell metabolic activity was assessed using the MTT assay, cell number using the SRB assay, and cell attachment from hepatocyte total protein content and protein synthesis using [14C]leucine incorporation. VEGF in culture supernatants was measured by ELISA. Tacrolimus and methylprednisolone had no statistically significant inhibitory effects on metabolic activity or protein synthesis compared to controls at all concentrations of the agents tested when added after plating. There were also no significant effects on cell attachment when tacrolimus or methylprednisolone was added at the time of cell plating. There were no differences in the responses obtained when either fresh or cryopreserved hepatocytes were used. The amount of VEGF secreted by untreated hepatocytes was highly variable (0-1400 pg/10(6) cells/24 h). VEGF levels in the culture supernatant from hepatocytes isolated from < or = 20-year-old donors (687 +/- 59 pg/10(6) cells/24 h) was significantly greater than from older donors (61 +/- 7 pg/10(6) cells/24 h; p = 0.003). Tacrolimus and methylprednisolone did not significantly affect VEGF secretion by hepatocytes. Tacrolimus and methylprednisolone did not have detrimental effects on the metabolic function of human hepatocytes, cell attachment, or VEGF secretion after cell isolation. PMID- 17269449 TI - Microencapsulation of engineered cells to deliver sustained high circulating levels of interleukin-6 to study hepatocellular carcinoma progression. AB - Interlukin-6 (IL-6) is a pleitropic cytokine that plays a central role in normal and abnormal hepatic function and response. The aims of the current study were to determine the viability of using cell encapsulation technology to introduce a genetically modified xenogeneic (CHO) cell population to elevate circulating levels of rhIL-6 in a rat model and determine the effects of sustained high rhIL 6 levels on hepatocellular carcinoma (HCC) progression in vivo. An alginate matrix was combined with transfected CHO cells, selected for their ability to synthesize rhIL-6, and used to generate uniform alginate-cell beads. Once encapsulated transfected cells continued to undergo replication, formed colonies within the bead, and synthesized/released large quantities of rhIL-6 into culture medium in vitro. Intraperitoneal implantation of beads into rats resulted in significantly increased circulating and intrahepatic levels of rhIL-6 up to 4 days postimplantation. Prolonged implantation led to the escape of CHO cells from the bead, resulting in a host response and CHO cell death within the bead. Subsequently CHO-IL-6 encapsulated cells were implanted into rats previously inoculated intrahepatically with the H4IIE HCC cell line. These studies demonstrated the maintenance of high circulating/intrahepatic rhIL-6 levels in this model. Despite significantly increased rhIL-6, this technique did not significantly alter the rate of net tumor progression. However, Stat3 activity was significantly increased in both normal liver and HCC tissue resected from animals implanted with CHO-IL-6 cells. Collectively these data demonstrate the short-term viability of using cell encapsulation technology to generate high levels of active circulating and intrahepatic cytokines and raise the possibility of modifying specific signal transduction cascades identified to be important during tumor progression. PMID- 17269450 TI - Enhanced functional maturation of fetal porcine hepatocytes in three-dimensional poly-L-lactic acid scaffolds: a culture condition suitable for engineered liver tissues in large-scale animal studies. AB - To engineer liver tissues with a clinically significant size, in vivo evaluation of performance using large-scale animal studies are necessary before proceeding to human clinical trials. As pigs are the most suitable candidates, the development of culture conditions suitable for porcine hepatocyte progenitors is very important to engineer pig liver tissue equivalents. We therefore investigated the efficacy of poly-L-lactic acid (PLLA) three-dimensional (3D) scaffolds on the functional maturation of fetal porcine hepatocytes in the presence of various combinations of biofactors. Cells were isolated from pig fetuses obtained from a local slaughterhouse, and cultured for 15 days both in monolayer and PLLA scaffolds. Although 15 days of culture resulted in almost the same ratio of proliferation (about fivefold) in both monolayer and 3D PLLA culture, the PLLA culture with hepatocyte growth factor (HGF, 10 ng/ml) and sodium butylate (Sb, 1 mM) remarkably enhanced various liver-specific functions of fetal porcine hepatocytes. The final attained functions based on the numbers of immobilized cells on day 1 compared with those of day 1 monolayers; 191-fold increase in albumin secretion, 70.5-fold increase in cytochrome P450 IA1/2 capacity, 20.9-fold increase in ammonia removal, and 18.0-fold increase in urea synthesis were obtained. These functions were 2.0-3.3-fold higher than those obtained by the same period of monolayer culture. In addition, final attained unit cell-based functions on day 15 were almost comparable to the levels reported for cultures of adult porcine hepatocytes in both monolayer and 3D spheroid cultures. These results demonstrate that the use of a biodegradable polymer-based 3D culture with an appropriate combination of biofactors is a promising approach to maximize functional maturation of hepatocyte progenitors from large animals. In addition, the established culture conditions are worth using to engineer large liver tissue equivalents for pigs in large-animal-based preclinical studies. PMID- 17269451 TI - In vitro functionality of human fetal liver cells and clonal derivatives under proliferative conditions. AB - Mature human hepatocytes are not suitable for large-scale in vitro applications that rely on hepatocyte function, due to their limited availability and insufficient proliferation capacity in vitro. In contrast, human fetal liver cells (HFLC) can be easily expanded in vitro. In this study we evaluated the hepatic function of HFLCs under proliferative conditions, to determine whether HFLCs can replace mature hepatocytes for in vitro applications. HFLCs were isolated from fetal livers of 16 weeks gestation. Hepatic functions of HFLCs were determined in primary culture and after expansion in vitro. Clonal derivatives were selected and tested for hepatic functionality. Results were compared to primary mature human hepatocytes in vitro. No differences were observed between primary HFLCs and mature human hepatocytes in albumin production and mRNA levels of various liver-specific genes. Ureagenesis was 4.4-fold lower and ammonia elimination was absent in HFLCs. Expanding HFLCs decreased hepatic functions and increased cell stretching. In contrast, clonal derivatives had stable functionality and morphology and responded to differentiation stimuli. Although their hepatic functions were higher than in passaged HFLCs, functionality was at least 20 times lower compared to mature human hepatocytes. HFLCs cannot replace mature human hepatocytes in in vitro applications requiring extensive in vitro expansion, because this is associated with decreased hepatic functionality. Selecting functional subpopulations can, at least partly, prevent this. In addition, defining conditions that support hepatic differentiation is necessary to obtain HFLC cultures suitable for in vitro hepatic applications. PMID- 17269452 TI - Development, characterization, and use of a fetal skin cell bank for tissue engineering in wound healing. AB - Wound healing in fetal skin is characterized by the absence of scar tissue formation, which is not dependent on the intrauterine environment and amniotic fluid. Fetal cells have the capacity of extraordinary expansion and we describe herein the development of a fetal skin cell bank where from one organ donation (2 4 cm2) it is possible to produce several hundred million fetal skin constructs of 9 x 12 cm2. Fetal cells grow three to four times more rapidly than older skin cells cultured in the same manner and these banked fetal cells are very resistant against physical and oxidative stress when compared to adult skin cells under the same culture conditions. They are up to three times more resistant to UVA radiation and two times more resistant towards hydrogen peroxide treatment. This mechanism may be of major importance for fetal cells when they are delivered to hostile wound environments. For fetal cell delivery to patients, cells were associated with a collagen matrix to form a three-dimensional construct in order to analyze the capacity of these cells for treating various wounds. We have seen that fetal cells can modify the repair response of skin wounds by accelerating the repair process and reducing scarring in severe bums and wounds of various nature in children. Hundreds of thousands of patients could potentially be treated for acute and chronic wounds from one standardized and controlled cell bank. PMID- 17269453 TI - Induction of tolerance across fully mismatched barriers by a nonmyeloablative treatment excluding antibodies or irradiation use. AB - A mixed-chimerism approach is a major goal to circumvent sustained immunosuppression, but most of the proposed protocols need antibody treatment or host irradiation. Another promising experience involves busulfan combined with cyclophosphamide treatment. Additionally, recent publications demonstrated that, differing from busulfan, treosulfan administration does not present severe organ or hemato toxicities. Currently, Duchenne muscular dystrophy (DMD) patients are treated with chronic immunosuppression for muscle precursor cell transplantation (MT). We have developed a safe tolerance approach within this cellular allotransplantation therapy background. Thus, we have conditioned, prior to a donor BALB/c MT, the dystrophic mouse model C57Bl10J mdx/mdx, with our treatment based on a donor-specific transfusion, then a treosulfan treatment combined with single cyclophosphamide dose, and finally a donor bone marrow transplantation (TTCB). A first MT was performed in all mixed chimeric mice resulting from the TTCB treatment in the left tibialis anterior (TA) muscles. A second MT from the same donor strain was performed 100 days later in the right TA without any additional therapy. Results show that all treated mice developed permanent mixed chimerism. Long-lasting donor-positive fibers were present in both TAs of the mice, which received MT after the TTCB treatment. Only a basal level of infiltration was observed around donor fibers and mixed chimeric mice rejected third-party haplotype skin grafts. Thus, mixed chimerism development with this TTCB conditioning regimen promotes donor-specific stable tolerance, avoiding costimulatory blockade antibodies or irradiation use and side effects of sustained immunosuppressive treatments. This protocol could be eventually applied for MT to DMD patients or others tissue transplantations. PMID- 17269454 TI - Characterizing sediment acid volatile sulfide concentrations in European streams. AB - Sediment acid volatile sulfide (AVS) concentrations were measured in wadeable streams of a wide variety of ecoregions of western Europe (84 sites in 10 countries and nine ecoregions) to better understand spatial distribution and ecoregion relationships. Acid volatile sulfide has been shown to be a major factor controlling the bioavailability and toxicity of many common trace metals, such as Cd, Cu, Ni, Pb, and Zn. Sediment characteristics varied widely. The ratio of the sum of the simultaneously extracted metals (SEM) to AVS ranged from 0.03 to 486.59. The sigmaSEM-AVS ranged from -40.02 to 17.71 micromol/g. On a regional scale, sediment characteristics such as dominant parent soil material showed significant trends in AVS distribution and variation by ecoregion. Total Fe and Mn were correlated weakly with SEM concentrations. Three AVS model approaches (i.e., the SEM:AVS ratio, SEM-AVS difference, and carbon normalization) were compared at threshold exceedance levels of SEM/AVS > 9, SEM-AVS > 2, and SEM AVS/foc > 150 micromol/g organic carbon (OC). Only 4.76% of the sediments exceeded all three AVS thresholds; 22.6% of the sediments exceeded two models; and 13% of the sediments exceeded one model only. Using the SEM:AVS, SEM-AVS, and fraction of organic carbon models, and including site-specific data and regional soil characteristics, ecoregions 1 (Portugal), 3 (Italy), 4 (Switzerland), and 9 (Belgium/Germany) had the highest potential metals toxicity; ecoregions 13 and 8 (Belgium/France) showed the lowest potential toxicity. However, because AVS can vary widely spatially and temporally, these data should not be considered as representative of the sampled ecoregions. The general relationship between AVS levels and sediment characteristics provides some predictive capability for wadeable streams in the European ecoregions. PMID- 17269455 TI - Predicting World Health Organization toxic equivalency factor dioxin and dioxin like polychlorinated biphenyl levels in farmed Atlantic salmon (Salmo salar) based on known levels in feed. AB - Assimilation and elimination rate constant of dietary polychlorinated dibenzo-p dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DLPCBs) with a World Health Organization toxic equivalency factor (WHO-TEF) were estimated in market-size Atlantic salmon (Salmo salar) using fish that were previously fed vegetable oil-based (low in PCDD/Fs and DLPCBs) or fish oil-based (high in PCDD/Fs and PCBs) diets. At the start of the kinetic trial, half the fish that were fed fish oils were fed vegetable oil feeds and inverted (cross over design) for five months. The assimilation efficiencies of the PCDD/F congeners were more variable (3-89%) and, generally, were lower than those of the DLPCBs (70-80%). Among the PCDD/F congeners, the assimilation efficiency of the most toxic tetra- and pentachlorinated PCDD/Fs was greater than that of higher chlorinated PCDD/Fs. Elimination rates for DLPCBs were higher than those for PCDD/Fs. Lower-chlorinated PCDDs had a lower elimination rate than the higher chlorinated PCDDs, but no differences were observed among PCDF congeners or DLPCB congeners. Kinetic parameters were used to predict the level of WHO-TEF dioxins and DLPCBs in Atlantic salmon reared in a large-scale facility under commercial conditions. Predictions were based on preanalyzed levels of these organochlorines in feeds with three different replacement levels (0, 30, and 60%) of vegetable oil. A simple one-compartmental, first-order kinetic model was used to predict the level of sum WHO toxic equivalents for PCDD/Fs and DL-PCBs. The predicted values varied by 0 to 11% from the measured values in the commercially reared salmon. PMID- 17269456 TI - Predicting the toxicity of neat and weathered crude oil: toxic potential and the toxicity of saturated mixtures. AB - The toxicity of oils can be understood using the concept of toxic potential, or the toxicity of each individual component of the oil at the water solubility of that component. Using the target lipid model to describe the toxicity and the observed relationship of the solubility of oil components to log (Kow), it is demonstrated that components with lower log (Kow) have greater toxic potential than those with higher log (Kow). Weathering removes the lower-log (Kow) chemicals with greater toxic potential, leaving the higher-log (Kow) chemicals with lower toxic potential. The replacement of more toxically potent compounds with less toxically potent compounds lowers the toxicity of the aqueous phase in equilibrium with the oil. Observations confirm that weathering lowers the toxicity of oil. The idea that weathering increases toxicity is based on the erroneous use of the total petroleum hydrocarbons or the total polycyclic aromatic hydrocarbons (PAHs) concentration as if either were a single chemical that can be used to gauge the toxicity of a mixture, regardless of its makeup. The toxicity of the individual PAHs that comprise the mixture varies. Converting the concentrations to toxic units (TUs) normalizes the differences in toxicity. A concentration of one TU resulting from the PAHs in the mixture implies toxicity regardless of the specific PAHs that are present. However, it is impossible to judge whether 1 microg/L of total PAHs is toxic without knowing the PAHs in the mixture. The use of toxic potential and TUs eliminates this confusion, puts the chemicals on the same footing, and allows an intuitive understanding of the effects of weathering. PMID- 17269457 TI - Transplacental transfer of organochlorines in California sea lions (Zalophus californianus). AB - The transplacental transfer of organochlorines (OCs) in California sea lions (Zalophus californianus) was investigated by analyzing blubber samples from 20 female sea lions and their fetuses during the last trimester of pregnancy. A rapid, high-performance liquid chromatographic, photodiode-array method was used to measure blubber concentrations of polychlorinated biphenyls (PCBs), including dioxin-like congeners, as well as DDTs and hexachlorobenzene. Summed values of PCBs (sigmaPCBs), of DDTs (sigmaDDTs), and of PCB toxic equivalents (sigmaPCB TEQs) were calculated from these data. The ratios of mean blubber concentrations of fetal sigmaPCBs to maternal blubber concentrations of sigmaPCBs were 0.45 by wet weight and 0.97 by lipid weight, but these ratios varied widely among mother fetus pairs. Mean ratios of fetal sigmaDDTs to maternal sigmaDDTs were 0.53 by wet weight and 1.12 by lipid weight. Fetuses were classified into two age groups, based on date of recovery, to examine differences in OC transfer because of gestational age. Fetal to maternal ratios for individual PCB congeners, DDT compounds, and sigmaPCBs, sigmaDDTs, and sigmaPCB TEQs were lower among premature compared with late-term fetuses. These ratios increased for both groups as the logarithmic n-octanol/water partition coefficient (log Kow) for each compound decreased. Linear predictions for sigmaPCB and sigmaDDT concentrations in fetal blubber could be obtained using the sigmaPCB and sigmaDDT concentrations in maternal blubber, maternal and fetal blubber lipid content, maternal mass, and maternal age. Fetal TEQ was explained by maternal TEQ and maternal age. The ability to predict contaminant concentrations in fetal blubber from maternal parameters is important for developing risk assessment models for marine mammals. PMID- 17269458 TI - Biofilm and mercury availability as key factors for mercury accumulation in fish (Curimata cyprinoides) from a disturbed Amazonian freshwater system. AB - The Petit-Saut hydroelectric reservoir was filled in 1994 on the Sinnamary River in French Guiana (Amazonian basin). Flooding of the equatorial rain forest led to anoxia in most of the water column and enhanced mercury methylation in the reservoir hypolimnion. We selected the benthivorous/omnivorous fish species Curimata cyprinoides to investigate total mercury and methylmercury (MeHg) bioavailability and bioaccumulation capacities in the reservoir and downstream in the Sinnamary River. Mercury concentrations in the dorsal skeletal muscle were 10 fold higher in fish from the downstream zone. Stomach contents and stable nitrogen and carbon isotope ratios showed that biofilms and the associated invertebrate communities represented important food sources at the two sites. The delta 13C measurements indicated that biofilms in the flooded forest zone of the reservoir consist of endogenous primary producers; downstream, they are based on exogenous organic matter and microorganisms, mainly from the anoxic layers of the reservoir. Total mercury and MeHg concentrations in the biofilms and associated invertebrates were much higher at the downstream site compared to concentrations at the reservoir. Our results clearly show the importance of MeHg export from the anoxic layers of this tropical reservoir. We conclude that differences between biofilm composition and MeHg concentrations in the ingested food could explain the marked differences observed between mercury levels in fish. PMID- 17269459 TI - Evasion of added isotopic mercury from a northern temperate lake. AB - Isotopically enriched Hg (90% 202Hg) was added to a small lake in Ontario, Canada, at a rate equivalent to approximately threefold the annual direct atmospheric deposition rate that is typical of the northeastern United States. The Hg spike was thoroughly mixed into the epilimnion in nine separate events at two-week intervals throughout the summer growing season for three consecutive years. We measured concentrations of spike and ambient dissolved gaseous Hg (DGM) concentrations in surface water and the rate of volatilization of Hg from the lake on four separate, week-long sampling periods using floating dynamic flux chambers. The relationship between empirically measured rates of spike-Hg evasion were evaluated as functions of DGM concentration, wind velocity, and solar illumination. No individual environmental variable proved to be a strong predictor of the evasion flux. The DGM-normalized flux (expressed as the mass transfer coefficient, k) varied with wind velocity in a manner consistent with existing models of evasion of volatile solutes from natural waters but was higher than model estimates at low wind velocity. The empirical data were used to construct a description of evasion flux as a function of total dissolved Hg, wind, and solar illumination. That model was then applied to data for three summers for the experiment to generate estimates of Hg re-emission from the lake surface to the atmosphere. Based on ratios of spike Hg to ambient Hg in DGM and dissolved total Hg pools, ratios of DGM to total Hg in spike and ambient Hg pools, and flux estimates of spike and ambient Hg, we concluded that the added Hg spike was chemically indistinguishable from the ambient Hg in its behavior. Approximately 45% of Hg added to the lake over the summer was lost via volatilization. PMID- 17269460 TI - Marine sediment toxicity identification evaluation methods for the anionic metals arsenic and chromium. AB - Marine sediments accumulate a variety of contaminants and, in some cases, demonstrate toxicity because of this contamination. Toxicity identification evaluation (TIE) methods provide tools for identifying the toxic chemicals causing sediment toxicity. Currently, whole-sediment TIE methods are not available for anionic metals like arsenic and chromium. In the present paper, we describe two new anion-exchange resins used in the development of whole-sediment TIE methods for arsenic and chromium. Resins were shown to reduce whole-sediment toxicity and overlying water concentrations of the anionic metals. Sediment toxicity, expressed as the median lethal concentration, was reduced by a factor of two to a factor of nearly six between amended sediment treatments containing resin and those without resin. Aqueous concentrations of arsenic and chromium in the toxicity exposures decreased to less than the detection limits or to concentrations much lower than those measured in treatments without resin. Interference studies indicated that the anion-exchange resins had no significant effect on concentrations of the representative pesticide endosulfan and minimal effects on concentrations of ammonia. However, the anion-exchange resins did significantly reduce the concentrations of a selection of cationic metals (Cd, Cu, Ni, Pb, and Zn). These data demonstrate the utility of anion-exchange resins for determining the contribution of arsenic and chromium to whole-sediment toxicity. The present results also indicate the importance of using TIE methods in a formal TIE structure to ensure that results are not misinterpreted. These methods should be useful in the performance of marine whole-sediment TIEs. PMID- 17269461 TI - Aquatic toxicity of ethoxylated and propoxylated alcohols to daphnia magna. AB - Ethoxylated alcohols, which are used as nonionic surfactants, are known to act as general narcotics in acute aquatic toxicity; that is, they behave in the same way as nonsurfactant unreactive organic chemicals. The toxicity of such chemicals is well predicted by quantitative structure-activity relationships based solely on the logarithm of the octanol/water partition coefficient (log P), which can be calculated from structure. In the present study, we have shown, using experimental results, that a similar approach can be used to determine the toxicity of ethoxylate/propoxylate alcohols (i.e., containing propoxy [PO] and ethoxy [EO] units). Our calculations indicate that use of the Roberts position dependent branching factor in calculating the PO group contribution is more appropriate than the Leo and Hansch branch factor. The resulting log P value for a PO group is 0.01; that is, the overall contribution to the final log P value is close to zero. On this basis, it is predicted that nonionic surfactants containing both EO and PO groups should have the same molar toxicity as surfactants based on the same parent alcohol and with the same number of EO groups but with no PO groups. This prediction has been confirmed in Daphnia acute toxicity tests. Furthermore, both EO/PO and EO-only nonionics are found to fit the same linear relationship between log P and toxicity. PMID- 17269462 TI - Increased response to cadmium and Bacillus thuringiensis maize toxicity in the snail Helix aspersa infected by the nematode Phasmarhabditis hermaphrodita. AB - To determine the effect of nematode infection on the response of snails to selected toxins, we infected Helix aspersa with 0-, 0.25-, 1-, or 4-fold the recommended field dose of a commercial nematode application for agricultural use. In the first experiment, the snails also were exposed to cadmium via food and soil at concentrations of 0, 30, 60, 120, or 240 mg/kg in a full-factorial design. In the second experiment, snails were infected with nematodes and also fed either Bt (expressing Bacillus thuringiensis toxin) maize or non-Bt maize. The snails were weighed at the beginning and end (after four weeks) of the experiments, and mortality was checked daily. Neither exposure of snails to nematodes nor exposure of snails to cadmium or Bt toxin affected the survival rates of snails. The number of dead snails was highest for combinations of nematode treatments with cadmium concentrations of 120 and 240 mg/kg. In both experiments (Bt and cadmium), the growth rate decreased with increasing nematode dose. The Bt maize was not harmful to the snails in the absence of nematodes, but infected snails grew faster when fed non-Bt maize. The growth rate of snails exposed to cadmium decreased with exposure to increasing Cd concentrations and differed significantly between the no-nematode treatment and the treatments with nematode doses of one- and fourfold the recommended field dose. Snails treated with the highest dose of nematodes accumulated the highest cadmium concentrations. PMID- 17269463 TI - Atrazine is an immune disruptor in adult northern leopard frogs (Rana pipiens). AB - Atrazine, the most widely used herbicide in the United States, has been shown in several studies to be an endocrine disruptor in adult frogs. Results from this study indicate that atrazine also functions as an immune disruptor in frogs. Exposure to atrazine (21 ppb for 8 d) affects the innate immune response of adult Rana pipiens in similar ways to acid exposure (pH 5.5), as we have previously shown. Atrazine exposure suppressed the thioglycollate-stimulated recruitment of white blood cells to the peritoneal cavity to background (Ringer exposed) levels and also decreased the phagocytic activity of these cells. Unlike acid exposure, atrazine exposure did not cause mortality. Our results, from a dose-response study, indicate that atrazine acts as an immune disruptor at the same effective doses that it disrupts the endocrine system. PMID- 17269464 TI - Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans. AB - Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications, primarily in the treatment of clinical depression. They are among the pharmaceuticals most often prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds with an identical mechanism of action in mammals (inhibit reuptake of serotonin), and they have been found in different aqueous as well as biological samples collected in the environment. In the present study, we tested the toxicities of five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) as single substances and of citalopram, fluoxetine, and sertraline in binary mixtures in two standardized bioassays. Test organisms were the freshwater algae Pseudokirchneriella subcapitata and the freshwater crustacean Daphnia magna. In algae, test median effect concentrations (EC50s) ranged from 0.027 to 1.6 mg/L, and in daphnids, test EC50s ranged from 0.92 to 20 mg/L, with sertraline being one of the most toxic compounds. The test design and statistical analysis of results from mixture tests were based on isobole analysis. It was demonstrated that the mixture toxicity of the SSRIs in the two bioassays is predictable by the model of concentration addition. Therefore, in risk assessment based on chemical analysis of environmental samples, it is important to include the effect of all SSRIs that are present at low concentrations, and the model of concentration addition may be used to predict the combined effect of the mixture of SSRIs. PMID- 17269465 TI - Effects of the estrogen agonist 17beta-estradiol and antagonist tamoxifen in a partial life-cycle assay with zebrafish (Danio rerio). AB - A partial life-cycle assay (PLC) with zebrafish (Danio rerio) was conducted to identify endocrine-disrupting effects of 17beta-estradiol (E2) and tamoxifen (TMX) as reference for estrogen agonist and antagonist activity. Adult zebrafish were exposed for 21 d and offspring for another 42 d, allowing differentiation of gonads in control animals. The assessed end points included reproductive variables (egg production, fertilization, and hatching), gonad differentiation of juveniles, histopathology, and vitellogenin (VTG) expression. With E2, the most sensitive end points were feminization of offspring (at 0.1 nM) and increased VTG production in males (at 0.32 nM). At 1 nM, decreased F, survival, increased F, body length and weight, VTG-related edema and kidney lesions, and inhibited spermatogenesis were observed. Oocyte atresia occurred at even higher concentrations. Exposure to TMX resulted in specific effects at an intermediate test concentration (87 nM), including oocyte atresia with granulosa cell transformation and disturbed spermatogenesis (asynchrony within cysts). In F1, decreased hatching, survival, and body weight and length as well as decreased feminization were observed. Decreased vitellogenesis and egg production in females and clustering of Leydig cells in males occurred at higher concentrations. Toxicological profiles of estrogen agonists and antagonists are complex and specific; a valid and refined characterization of endocrine activity of field samples therefore can be obtained only by using a varied set of end points, including histology, as applied in the presented PLC. Evaluation of only a single end point can easily produce under- or overestimation of the actual hazard. PMID- 17269466 TI - Hepatic responses of gene expression in juvenile brown trout (Salmo trutta lacustris) exposed to three model contaminants applied singly and in combination. AB - Chemical pollution of the aquatic environment is almost always the result of multiple rather than single toxic compounds. The possibility of separating the effects of key risk chemicals from those of others, including theirjoint effects, is of clear theoretical interest and high technical importance. We addressed this goal using multiple gene expression profiling in the liver of juvenile brown trout (Salmo trutta lacustris) exposed to three model chemicals (cadmium, carbon tetrachloride [CCl4], and pyrene) administered singly, in binary and trinary combinations at low acutely sublethal concentrations, and in the partial dose response manner. Differentially expressed genes were grouped by correlation of profiles, and the dependence on dose was analyzed with multiple regression. Responses to cadmium and CCl4 were largely similar, and no sign of interaction was observed (i.e., in binary combinations, the effects were equal to those produced by the more potent compound, cadmium). Joint effects became apparent in the presence of pyrene, which caused markedly different alterations in gene expression. Using the results of 118 experiments conducted earlier for comparison, we found a group of 23 genes responding to chemical toxicity (cadmium, CCl4, pyrene, and resin acids) with significantly higher probability than that of responding to other stressors (handling or viral and bacterial infections). This group included genes implicated in the immune and stress responses that were markedly enriched in extracellular proteins. In conclusion, we demonstrated that chemical-characteristic genomic endpoints often remain when the chemical is present as part of a binary or a trinary mixture. Despite dissimilar chemistry and different cellular targets, the degree of responses to the combination of cadmium and CCl4 appeared to be less than additive. Chemical interactions or nonadditive effects manifested when a compound with a markedly different mode of action (pyrene) was included into the mixture. PMID- 17269467 TI - Expression pattern of metallothionein, MTF-1 nuclear translocation, and its dna binding activity in zebrafish (Danio rerio) induced by zinc and cadmium. AB - Metallothionein is a small (6-kDa), cysteine-rich protein expressed by a six-zinc finger protein called metal-responsive element-binding transcription factor-1 (MTF-1) in response to Zn and Cd. Our previous reports have shown the basal expression of metallothionein (mt) and MTF-I (mtf-1) genes in embryo and early larval stages of zebrafish (Danio rerio). In the present study, we investigated the mt expression in zebrafish early larvae induced by exposure to Cd and Zn (48, 72, 96, and 120 h postfertilization). Whole-mount in situ hybridization showed that Zn induced mt expression in the olfactory pit, cerebellum, ceratobranchials, liver, chloride cells, and neuromasts of the lateral line. Cadmium also induced mt expression in all the above regions except the cerebellum. Using fluorescence techniques, we have shown that Zn and Cd mediate cytoplasmic and nuclear translocation of MTF- 1-enhanced green fluorescent protein fusion protein in zebrafish liver cell line. The MTF-1 protein was produced recombinantly by inserting zebrafish mtf-1 cDNA (1.8 kb) into pET-20b(+) expression vector and expressing in Escherichia coli BL21 (DE3) pLysS host strain competent cell on induction with isopropyl-beta-D-thiogalactopyranoside. The protein was then purified by affinity chromatography on a nickel-nitrilotriacetic acid column. Electrophoretic mobility shift assay revealed binding of the recombinant MTF-1 in response to Zn and Cd at the putative metal-responsive elements (MREs) in the promoter region of the mt gene. Taken together, these results suggest that Zn and Cd are efficiently involved with mt expression induced in zebrafish embryos and with MTF-1 nuclear translocation and that this induction is achieved through the activation of MTF-1 binding at the MREs. PMID- 17269468 TI - Mercury bioaccumulation in green frog (Rana clamitans) and bullfrog (Rana catesbeiana) tadpoles from Acadia National Park, Maine, USA. AB - Mercury contamination in the northeastern United States, including Acadia National Park (ANP; ME, USA), is well documented and continues to be a public health issue of concern. Mercury contamination of wild amphibians has received little attention, however, despite reports of worldwide population declines. Here, we report total Hg and methyl Hg (MeHg) concentrations for water, sediment, and green frog (Rana clamitans) and bullfrog (Rana catesbeiana) tadpoles (age, approximately one year) from ANP. Total Hg concentrations (mean+/-standard error) in green frog and bullfrog tadpoles were 25.1+/-1.5 and 19.1+/-0.8 ng/g wet weight, respectively. Mean total Hg was highest for green frog tadpoles sampled from the Schooner Head site (ANP, Bar Harbor, ME, USA), a small, semipermanent beaver pond where Ranavirus was detected during the summer of 2003 sampling period. Methyl Hg comprised 7.6 to 40% of the total Hg in tadpole tissue (wet-wt basis), and mean total Hg levels in tadpoles were significantly different among pond sites (n = 9). Total Hg in pond water was a significant predictor of tadpole total Hg levels. Dissolved organic carbon was a significant predictor of both total Hg and MeHg in water, and total Hg in water also was strongly correlated with MeHg in water. Of the nine pond ecosystems sampled at ANP 44% had a methylation efficiency (water MeHg to total Hg ratio) of greater than 10%, and 33% had total Hg levels in sediment that were approximately equal to or greater than the established threshold level effect concentration for freshwater sediments (0.174 mg/kg dry wt). Our data indicate that wetland food webs in ANP likely are susceptible to high levels of total Hg bioaccumulation and that methylation dynamics appear to be influenced by local abiotic and biotic factors, including disturbances by beavers and in situ water chemistry patterns. These findings may be important to National Park Service resource managers, especially considering the class I airshed status of ANP and the strong potential for negative effects to aquatic ecosystem structure and function from Hg pollution. PMID- 17269469 TI - Reproductive toxicity of dietary copper to a saltwater cladoceran, Moina monogolica Daday. AB - In the present study, the chronic toxicity of dietary copper to Moina monogolica Daday was investigated. Microalgal growth inhibition tests were conducted for 96 h with the green algae Chlorella pyrenoidosa exposed to copper. The 96-h median effective concentration (95% confidence interval) was 509.12 (388.68-629.56) microg/L. Then, C. pyrenoidosa was exposed for 96 h to a control and to seven dissolved copper concentrations. Cellular copper concentration accumulated in a dose-dependent manner and was plotted against cell density. These algae were used as food in a 21-d bioassay with M. monogolica in seawater to which no dissolved copper was added. Brood size was not reduced in the first brood, but significant reductions at all algal-exposure copper concentrations (44.78-817.17 microg/L) were observed in all subsequent broods, with increasing magnitude in each brood. Neither longevity nor number of broods per female was significantly affected, even at the highest copper exposure, though both endpoints did show a consistent downward trend with increasing copper exposure. Total reproduction, brood size, and net reproductive rate were decreased significantly in all dietary copper exposures (algae exposed to 44.78-817.17 microg/L). In contrast, the intrinsic rate of natural increase was reduced significantly only with algae exposed to greater than 619.27 microg/L, most likely because of the heavy influence of early reproduction on this metric. Because cell density in algal cultures decreased with increasing copper concentrations, it is possible that changes in the nutritional content of the algal diet could have played a role in causing the observed changes in reproduction of M. monogolica. PMID- 17269470 TI - An integrated model describing the toxic responses of Daphnia magna to pulsed exposures of three metals. AB - Some toxicology research in which toxicant exposures are continual (pulsed) rather than continuous have been reported. A number of toxicity models have been developed for pulsed and continuous exposures. Most of these models were developed based on one- or two-compartment, first-order toxicokinetics and were calibrated with organic compounds. In the present study, the relationship between mortality (after 21 d) of Daphnia magna in response to pulsed and continuous exposures to Cu, Zn, and Se was used to develop a model that integrated the effects of single and multiple pulsed metal exposures based on first-order uptake and depuration kinetics. Mortality was a function of exposure concentration, duration, and recovery time between exposures. The model was successfully validated using an independent data set. It is applicable to risk assessment and, potentially, may be incorporated with other models (e.g., the biotic ligand model) to predict the toxicity of pulsed metal exposures under a range of environmental conditions. PMID- 17269471 TI - Response spectrum of fluoranthene and pentachlorobenzene for the fathead minnow (Pimephales promelas). AB - Internal body residue has been recognized as a potential dose metric for toxicological assessments. This relationship between body residue and biological effects, including both lethal and sublethal effects, is critically important for determining environmental quality in risk assessments. The present study identified the toxic equivalent body residues for fluoranthene (FLU) and pentachlorobenzene (PCBz) associated with mortality, reduced growth, and decreased hatchability in the fathead minnow. The toxic equivalent body residue was defined as the total of the parent compound and the organically extractable metabolites for FLU and of the parent compound only for PCBz, because no biotransformation was measurable. The lethal body residues corresponding to 50% mortality were 0.80 and 1.26 micromol/g wet weight for FLU and PCBz, respectively. As expected, residues associated with sublethal effects generally are 2- to 40-fold lower than the lethal residues for FLU and PCBz. Juvenile fish growth was the most sensitive endpoint examined for both compounds. The maximum allowable toxicant residues were 0.02 and 0.43 micromol/g wet weight for FLU and PCBz, respectively. The information collected from the present study will permit a greater understanding of residue-response relationships, which will be useful in risk assessments. PMID- 17269472 TI - Reproducibility of binary-mixture toxicity studies. AB - Binary-mixture studies often are conducted with the aim of elucidating the effect of one specific chemical on the biological action of another. The results can be interpreted in relation to reference models by the use of response-surface analyses and isobolograms. The amount of data needed for these analyses is, however, extensive, and the experiments therefore rarely are repeated. In the present study, we investigate the reproducibility of isobole shapes of binary mixture toxicity experiments in terms of deviation from the reference model of concentration addition (CA), dose-level dependence, and isobole asymmetry. We use data from four herbicide mixtures tested in three to five independent experiments on the aquatic test plant Lemna minor and the terrestrial plant Tripleurospermum inodorum. The results showed that the variation both within and among experiments was approximately half the size for the aquatic test system compared to the terrestrial system. As a consequence, a consistent deviation from CA could be obtained in three of four herbicide mixtures for L. minor, whereas this was only the case for one or two of the herbicide mixtures tested on T. inodorum. For one mixture on T. inodorum, both CA synergism and antagonism were detected. Dose dependent effects could not be repeated consistently, just as the asymmetry found in some isoboles could not. The study emphasizes the importance of repeating mixture toxicity experiments, especially for test systems with large variability, and using caution when drawing biological conclusions from the test results. PMID- 17269473 TI - Differential sensitivity to Bacillus thuringiensis var. israelensis and temephos in field mosquito populations of Ochlerotatus cataphylla (Diptera: Culicidae): toward resistance? AB - In the present study, four populations of the same field mosquito species, Ochlerotatus cataphylla, were sampled over the Rh6ne-Alpes region (France), and their respective sensitivity to the organophosphate temephos and the bacterio insecticide Bacillus thuringiensis var. israelensis (Bti) was measured. The results obtained in toxicological tests showed significant differences in the larval sensitivities of the four populations for both insecticides. These differences appeared to be related to the activity of the three main families of detoxifying enzymes: Cytochrome P450 monooxygenases, glutathione-S-transferases (GSTs), and esterases. All three enzyme families were significantly overexpressed in the less susceptible larval population, and after multiple regressions, GSTs and esterases came out as the most explicative variables of the larval sensitivity. Considering these results and the chemical history of the sites in terms of insecticide treatments, the hypothesis of cross-effects of insecticides leading to resistance acquisition to Bti in field organisms emerges. PMID- 17269474 TI - Establishing cause-effect relationships in hydrocarbon-contaminated sediments using a sublethal response of the benthic marine alga, Entomoneis cf punctulata. AB - A sublethal whole-sediment toxicity test that uses flow cytometry to measure inhibition of esterase activity in the marine microalga Entomoneis cf punctulata was applied to the assessment of hydrocarbon-contaminated sediments and toxicity identification and evaluation (TIE). Concentration-response relationships were developed, and a 20% effect concentration for total polycyclic aromatic hydrocarbons (PAHs) of 60 mg/kg normalized to 1% total organic carbon was calculated. Relationships between toxic effects and sediment organic carbon concentrations, organic carbon forms (e.g., black carbon), and sediment particle size indicated that further normalization of hydrocarbon concentrations to sediment particle size may improve concentration-response relationships. The algal toxicity test was applied as a rapid whole-sediment TIE procedure that involved the addition to sediment of powdered coconut charcoal (PCC), a hydrophobic, carbon-based material that strongly adsorbs PAHs and decreases the pore-water exposure pathway. Sediments with PCC concentrations of up to 15% (w/w) provided acceptable responses in control sediments. For six sediments with total PAH concentrations of 1,060, 4,060, 5,120, 9,150, 9,900, and 15,900 mg/kg, inhibition of E. cf punctulata esterase activity (% of control) was 75, 97, 94, 93, 100, and 97%, respectively. Following a 15% PCC amendment to these sediments, inhibition of esterase activity was 0, 1, 11, 69, 32, and 68%, respectively, indicating a decrease in toxicity in all sediments. Because the alga E. cf punctulata is exposed to toxicants via both pore water and overlying water, the reduction in toxicity achieved by 15% PCC additions can be related to the efficient removal of dissolved hydrocarbons released from sediment particles. The sediment-PCC manipulations coupled with algal whole-sediment toxicity tests provided an effective and rapid TIE method to determine whether hydrocarbon contaminants are responsible for toxicity in sediments. PMID- 17269475 TI - Bioaccumulation of the hepatotoxic microcystins in various organs of a freshwater snail from a subtropical Chinese lake, Taihu Lake, with dense toxic Microcystis blooms. AB - In this paper, we describe the seasonal dynamics of three common microcystins (MCs; MC-RR, MC-YR, and MC-LR) in the whole body, hepatopancreas, intestine, gonad, foot, remaining tissue, and offspring of a freshwater snail, Bellamya aeruginosa, from Gonghu Bay of Lake Taihu, China, where dense toxic Microcystis blooms occur in the warm seasons. Microcystins were determined by liquid chromatography electrospray ionization mass spectrum. Microcystin (MC-RR + MC-YR + MC-LR) content of the offspring and gonad showed high positive correlation, indicating that microcystins could transfer from adult females to their young with physiological connection. This study is the first to report the presence of microcystins in the offspring of the adult snail. The majority of the toxins were present in the intestine (53.6%) and hepatopancreas (29.9%), whereas other tissues contained only 16.5%. If intestines are excluded, up to 64.3% of the toxin burden was allocated in the hepatopancreas. The microcystin content in the intestine, hepatopancreas, and gonad were correlated with the biomass of Microcystis and intracellular and extracellular toxins. Of the analyzed foot samples, 18.2% were above the tolerable daily microcystin intake recommended by the World Health Organization (WHO) for human consumption. This result indicates that public health warnings regarding human ingestion of snails from Taihu Lake are warranted. In addition, further studies are needed to evaluate the occurrence by Microcystis in relation to spatial and temporal changes in water quality. PMID- 17269476 TI - Risk assessment of Magnacide H herbicide at Rio Colorado irrigation channels (Argentina). Tier 3: studies on native species. AB - We evaluated the potential environmental risk of the herbicide Magnacide (Baker Petrolite, TX, USA) using native species from Argentina, representing the ecosystem at the Irrigation Corporation (CORFO) channels at the Colorado River mouth, Buenos Aires, Argentina. Six species including fish, toads, snails, crustaceans, and insects were selected to perform studies on acute toxicity and repeated exposure effects. Magnacide H susceptibility ranking was Bufo arenarum (lethal concentration 50 [LC50] = 0.023 mg/L), Onchorhynchus mykiss (LC50 = 0.038 mg/L), Heleobia parchappii (LC50 = 0.21 mg/L), Hyalella curvispina (LC50 = 0.24 mg/L), Simulium spp. (LC50 = 0.60 mg/L), and Chironomus spp. (LC50 = 2.83 mg/L). The risk limit of 10th percentile (0.013 mg/L) determined by probit analysis on sensitivity distribution was similar to the one calculated from literature data. Risk assessment based on field application data suggested lethal exposures for more than 70 to 90% of the species up to 20 km downstream from the application point. Repeated exposures to Magnacide H of amphibian larvae at the lowest observed-effect concentration caused some effects during the first exposure, but without cumulative effects. Amphipods were insensitive to repeated exposures, showing no cumulative effects. Whether short-term exposures may result in long term sublethal effects on the organism's life history was not addressed by these laboratory tests. In conclusion, tier 3 studies indicate that Magnacide H application schedule is extremely toxic for most native species at CORFO-Rio Colorado channels, representing a high potential risk in the environment. The real environmental impact must be addressed by field studies at tier 4 giving more information on population effects and communities. PMID- 17269478 TI - HHMM celebrates 20 years, looks to the future. PMID- 17269477 TI - Environmental effect assessment of Magnacide H herbicide at Rio Colorado irrigation channels (Argentina). Tier 4: in situ survey on benthic invertebrates. AB - The objective of this study was to assess the effects of Magnacide H (Baker Petrolite, TX, USA) usage on the aquatic ecosystem at the Cooperativa de Riego y Fomento (CORFO)-Rio Colorado irrigation channels, analyzing the effects on benthic invertebrates. At recommended treatment concentrations, Magnacide H kills most of the aquatic organisms; however, its presence in the channels is transient. Magnacide H caused a significant reduction in the number of taxa (58%), abundance (57%), and community diversity (67%) in the benthic assemblage with respect to untreated channels during the application period in the first year of the study. The herbicide reduced the abundance of the most abundant taxa: oligochaetes, chironomids, ostracods, and the snails Biomphalaria peregrina and Heleobia parchappii. In contrast, the herbicide only reduced invertebrate diversity during the application period at the second year of study. Two months after the applications had ceased, the benthic community in treated channels recovered their biotic attributes, reaching values similar to controls. Recovery could have occurred from upstream unimpaired reaches supplying migrating invertebrates that recolonized affected areas. Since recovery occurred within a reasonable period of time, we conclude that the impact of Magnacide H at CORFO Rio Colorado channels is acceptable from a regulatory point of view in the present practice protocol. Nevertheless, a strict control on the application conditions must be ensured to minimize the risk on the ecological receptors. We emphasize the recommendation that water release outside the channels is prevented until the product has dissipated. PMID- 17269479 TI - Follow these six steps to become a benchmarking process expert. PMID- 17269480 TI - A protozoan pays off. PMID- 17269481 TI - Stem cells. PMID- 17269482 TI - Computational protein design promises to revolutionize protein engineering. AB - Natural evolution has produced an astounding array of proteins that perform the physical and chemical functions required for life on Earth. Although proteins can be reengineered to provide altered or novel functions, the utility of this approach is limited by the difficulty of identifying protein sequences that display the desired properties. Recently, advances in the field of computational protein design (CPD) have shown that molecular simulation can help to predict sequences with new and improved functions. In the past few years, CPD has been used to design protein variants with optimized specificity of binding to DNA, small molecules, peptides, and other proteins. Initial successes in enzyme design highlight CPD's unique ability to design function de novo. The use of CPD for the engineering of potential therapeutic agents has demonstrated its strength in real life applications. PMID- 17269483 TI - EGFR artifactual mutations associated with two DNA sequencers. PMID- 17269484 TI - Synthesis of genes with multiple identical domains. PMID- 17269485 TI - Optimizing annealing temperature overcomes bias in bisulfite PCR methylation analysis. PMID- 17269486 TI - Use of intein-mediated phosphoprotein arrays to study substrate specificity of protein phosphatases. AB - Synthetic peptides incorporating various chemical moieties, for example, phosphate groups, are convenient tools for investigating protein modification enzymes, such as protein phosphatases (PPs). However, short peptides are sometimes poor substrates, and their binding to commonly used matrices is unpredictable and variable. In general, protein substrates for PPs are superior for enzymatic assays, binding to various matrices, and Western blot analysis. The preparation and characterization of phosphoproteins, however can be difficult and technically demanding. In this study, the intein-mediated protein ligation (IPL) technique was used to readily generate phosphorylated protein substrates by ligating a synthetic phosphopeptide to an intein-generated carrier protein (CP) possessing a carboxyl-terminal thioester with a one-to-one stoichiometry. The ligated phosphoprotein (LPP) substrate was treated with a PP and subsequently subjected to array or Western blot analysis with a phospho-specific antibody. This approach is highly effective in producing arrays of protein substrates containing phosphorylated amino acid residues and has been applied for screening of PPs with specificity toward phosphorylated tyrosine, serine, or threonine residues, resulting in an approximately 240-fold increase in sensitivity in dot blot analysis compared with the use of synthetic peptides. The IPL technique overcomes the disadvantages of current methods and is a versatile system for the facile production of protein substrates containing well-defined structural motifs for the study of protein modification enzymes. PMID- 17269487 TI - CellProfiler: free, versatile software for automated biological image analysis. AB - Careful visual examination of biological samples is quite powerful, but many visual analysis tasks done in the laboratory are repetitive, tedious, and subjective. Here we describe the use of the open-source software, CellProfiler, to automatically identify and measure a variety of biological objects in images. The applications demonstrated here include yeast colony counting and classifying, cell microarray annotation, yeast patch assays, mouse tumor quantification, wound healing assays, and tissue topology measurement. The software automatically identifies objects in digital images, counts them, and records a full spectrum of measurements for each object, including location within the image, size, shape, color intensity, degree of correlation between colors, texture (smoothness), and number of neighbors. Small numbers of images can be processed automatically on a personal computer and hundreds of thousands can be analyzed using a computing cluster. This free, easy-to-use software enables biologists to comprehensively and quantitatively address many questions that previously would have required custom programming, thereby facilitating discovery in a variety of biological fields of study. PMID- 17269488 TI - SNP-based chromosomal copy number ascertainment following multiple displacement whole-genome amplification. AB - Whole genome amplification by multiple displacement amplification (MDA) offers investigators using precious genomic DNA samples a high fidelity method for amplifying nanogram quantities of DNA several thousandfold. This becomes especially important for the modemrn day genomics researcher who more and more commonly is applying today's genome scanning technologies to patient cohort samples collected years ago that are irrecoverable and invariably in short supply. We present evidence here that MDA-prepared genomic DNA includes artifacts of chromosomal copy number that resemble copy number polymorphisms (CNPs) upon analysis of the DNA on the Affymetrix 10K GeneChip. The study of CNPs in both health and disease is a rapidly growing area of research, however our current understanding of the relevance of CNPs is incomplete. Our data indicate that utilization of whole genome-amplified samples for analysis heavily reliant on accurate copy number retention could be confounded if the genomic DNA sample was subjected to MDA. We recommend that small amounts of patient cohort DNA stocks be set aside and not subjected to whole genome amplification in order to facilitate the unbiased determination of chromosomal copy numbers when desired. PMID- 17269489 TI - Directed assembly of DNA molecules via simultaneous ligation and digestion. AB - DNA ligation is a routine laboratory practice, yet the yield of the desired product is often very low due to competing off-pathway reactions. The sensitivity of subsequent manipulations (e.g., selection via bacterial transformation) often obviates the need for a high yield of correctly ligated products. However the ability to perform high-yield, preparative-scale DNA ligations would benefit a number of downstream applications ranging from standard molecular cloning to biophysics and DNA computing. We describe here a ligation technique that specifically converts off-pathway ligation products back into substrate. We term this second-chance strategy enzymatic ligation assisted by nucleases (ELAN) and demonstrate the ordered assembly of four DNA fragments via simultaneous ligation and digestion in the presence of eight restriction enzymes. Use of ELAN increased the yield of the desired product by more than 30-fold. PMID- 17269490 TI - Beta-lactamase: an ideal reporter system for monitoring gene expression in live eukaryotic cells. AB - To gain insightful information about the mechanisms through which genes are activated and repressed requires gene reporter systems that are sensitive, robust, and cost-effective. Although numerous reporter gene technologies are commercially available, none are as sophisticated and user-friendly as beta lactamase (BLA) when it comes to studying gene expression in live cells. This article presents an overview of the BLA technology and describes how it can be exploited for studying rare events such as homologous recombination in somatic cells and be used to deliver any DNA sequence of choice anywhere within the genome. PMID- 17269491 TI - Mary Glover Lecture 2006: the contributions of neuroscience nursing to the field of quality of life. AB - The scholarly literature related to quality of life (QoL) is reviewed. Specific contributions by neurosciences nursing related to quality of life for patients and family caregivers is presented in the areas of stroke, neuro-oncology, traumatic brain injury, multiple sclerosis, and epilepsy. QoL information is important, as it is used in decisions concerning treatment and interventions for patients and their family members who are living with neurological conditions and their consequences. PMID- 17269492 TI - Eyes wide open: the awake craniotomy for tumour resection: a review. AB - The awake craniotomy procedure has become the gold standard for tumour resection in eligible patients. In this paper, the awake craniotomy procedure is reviewed, including the advantages of the procedure over the standard craniotomy procedure. The role of the neuroscience nurse in awake craniotomies is highlighted. PMID- 17269494 TI - [Wish medicine--the physician caught in the middle between medical importance and responsibility fo r patients]. PMID- 17269493 TI - [On the 100th anniversary of "Journal of Quality Assurance in Continuing Education and Health"]. PMID- 17269495 TI - [The patient--sufferer, partner or customer?]. AB - Over the past two decades, physicians in the German healthcare system have been forced by economic and socio-political developments to accept a far-reaching dependence on non-medical interest groups. An increasing bureaucratic burden and decreasing incomes as the two most obvious signs of these changes have led to widespread unrest and dissatisfaction. Patients too have been assigned new roles. In addition to their traditional definition as "sufferers", they are now considered self-conscious customers and partners. The present paper discusses these changes focussing on the patient, thereby complementing earlier papers by the same author that have been published under the title "The Physician as a Stranger in Medicine- from driving to being driven". The perspective applied is that of a medical historian who regards the present as a product of the past. Medicine has always been asked to fulfil "demands". What is new is the nature of the "demands" that can be expected by customer-patients to be met by medicine. Furthermore, patients and not-yet-patients may constitute a pillar of future economic growth rather than a burden for a country's economy. Public health policy as well as the roles of physicians and patients are gradually adapting to these novel circumstances. PMID- 17269496 TI - [A patient's wishes--the most important law?]. AB - It is a controversial issue in medicine whether the patient's wellbeing or wishes should qualify as treatment criteria. Through the denial of "paternalism" self determination has become a somewhat lopsided focus of attention. But the principle of caring and doing good is a determinant of clinical action, which is also guided by a respect for autonomy. Even the "medicine of desire" cannot be controlled by the patient's wishes alone. In each case a balance must be sought between these fundamentally equal principles. In aesthetic medicine, for example, merciless frankness and toughness--as has been expressed by the judiciary--may be indicated without further clarification. PMID- 17269497 TI - [Aesthetic surgery]. AB - The WHO describes health as physical, mental and social well being. Ever since the establishment of plastic surgery aesthetic surgery has been an integral part of this medical specialty. It aims at reconstructing subjective well-being by employing plastic surgical procedures as described in the educational code and regulations for specialists of plastic surgery. This code confirms that plastic surgery comprises cosmetic procedures for the entire body that have to be applied in respect of psychological exploration and selection criteria. A wide variety of opinions resulting from very different motivations shows how difficult it is to differentiate aesthetic surgery as a therapeutic procedure from beauty surgery as a primarily economic service. Jurisdiction, guidelines for professional conduct and ethical codes have tried to solve this question. Regardless of the intention and ability of the health insurances, it has currently been established that the moral and legal evaluation of advertisements for medical procedures depends on their purpose: advertising with the intent of luring patients into cosmetic procedures that do not aim to reconstruct a subjective physical disorder does not comply with a medical indication. If, however, the initiative originates with the patient requesting the amelioration of a subjective disorder of his body, a medical indication can be assumed. PMID- 17269498 TI - [Aesthetic dermatology]. AB - In addition to treating neoplastic disease, inflammatory skin disorders and allergies Aesthetic Dermatology has grown to become an important issue in the field of dermatology. Aesthetic Dermatology puts medicine in a field of tension between medical necessities and patients' wishes. Aesthetic issues are most relevant to dermatology because skin is not only a functional organ like heart, liver and kidneys, but a medium also of visual and tactile communication. The desire for beauty and youth is thus often expressed by patients and customers seeking advice on the improvement of their appearance and looks. Aesthetic medicine means a great challenge to the dermatologist because request and reality must be brought together and ethic thoughts kept in mind. Modern medicine with its new approaches to molecular biology and biophysical technologies (e.g. laser technology) has opened up many new therapeutic possibilities for dermatologists that were largely unimaginable until recently. Aesthetic dermatology has enriched dermatology and will not become a burden if we succeed with integrating aesthetic issues into medical strategies in a sensitive, evidence-based and critical fashion. PMID- 17269499 TI - [Aesthetic plastic surgery from a medical association's point of view]. AB - Influenced by rapidly changing ideals of beauty, more and more people are turning to aesthetic surgery to meet current standards of beauty. In this situation physicians have to balance the patient's wishes by correctly interpreting his psychological condition and gaining his informed consent. In some situations, an operation can and must be denied. To improve transparency and quality the Medical Association North-Rhine (Arztekammer Nordrhein) established a public register of "aesthetic surgery" ("Plastisch-Operative Medizin"). Patients searching qualified aesthetic surgery can choose from a list of suitable specialists. Initial experience seems to confirm acceptance of this concept. PMID- 17269500 TI - [Aesthetic medicine and aspects related to liability, medical professional and social law]. AB - There are no special legal arrangements for the field of aesthetic medicine; rather, the general medico-legal regulations apply although they raise specific questions as far as aesthetic medicine is concerned. Legally, a contract exists between physician and patient which is also applicable to aesthetic medicine. This means that the physician owes the patient only the provision of a proper, non-defective service, but does not need to guarantee that it actually leads to the desired outcome. Before performing a medically non-indicated procedure the physician is obliged to provide the patient with particularly thorough information about this procedure. Various problems and issues are raised by the advertising limitations for medical professionals and the maintenance of the boundaries confining the special field of aesthetic medicine. Medically indicated procedures are suitable for statutory reimbursement if the patient suffers from "physical disfigurement" or somatic complaints that lead to considerable impairment and if there are no other, cheaper treatment options available. PMID- 17269501 TI - [A controversial definition of the limitations on reproductive medicine in Germany]. AB - In principle, all kinds of sterility therapy can be defined as "medicine of desire". Stimulation, insemination, in-vitro fertilisation and ICSI are established methods and paid for by statutory health insurers. Some types of sterility therapy, though, are forbidden in Germany and thus form part of a "medicine of desire". These methods are only practised in foreign countries: oocyte donation, pre-implantational genetic diagnosis, embryo selection, surrogate motherhood, therapeutic cloning and preparation of embryonic stem cells. Taking oocyte donation as an example, the question of whether it is reasonable to ban oocyte donation will be discussed from a medical, psychological and ethical perspective. From the point of view of medicine, oocyte donation has proved to be successful with birth rates of 25-40% per cycle. No serious objections emerged from the follow-up of children, couples and the relationship between parents and children.The pros and cons of a more liberal and open handling should be discussed from an ethical point of view. Medically, psychologically and ethically the ban of oocyte donation in Germany does not seem to be justified. PMID- 17269502 TI - [Custom-made medicine: preimplantation genetic diagnosis]. AB - Who wants Preimplantation Genetic Diagnosis (PGD), who rejects it? The implications resulting from biological facts and legal regulations are addressed here. It is discussed under which conditions the restrictions of the Embryo Protection Act (Embryonenschutzgesetz, EschG) should be relaxed in order to be able to perform assisted reproduction technologies in Germany under international quality standards and also PGD in cases of stringent medical-genetic conditions. PMID- 17269503 TI - [Problems of the "Rule of 3"]. AB - The author discusses problems of the "Rule of 3" (Dreierregel) meaning that only three pre-embryos are allowed to be produced within one fertilisation process. This rule is based on the Embryo Protection Act and restricts methods of reproductive medicine. These limits have provoked a debate among the legal community on the question whether certain methods still conform to the law or if the law has to be adapted. This article both outlines and criticizes the arguments put forward in the debate and contrasts them to a proposal made by the German Medical Association. PMID- 17269504 TI - [Illegal though nonpunishable termination of pregnancy]. AB - This article addresses the valid abortion law, i.e., the regulation of sections 218 to 219b of the German Penal Code (StGB), especially Sect. 218 part 1 StGB legalising abortion after compulsory consultation within a limited period of time after conception ("Fristenregelung") which provides immunity from prosecution but no justification. Initially, the article outlines the currently valid law with particular consideration of sect. 218 part 1 StGB. The text also deals with the political problems of this regulation in the field of tension between the conflicting interests of the unborn child and the pregnant woman and leads to the symposium's subject, i.e. "medicine of desire". The writer deals with (1) the history of this regulation, which has been controversial for decades, while particular consideration is given to the decision made by the Federal Constitutional Court on 28th May 1993 (as the origin of the current law), and (2) its predominantly critical reception. The Federal Constitutional Court approved of a rule that refrains from punishing abortion in the early stage of pregnancy and focuses on the pregnant woman's counselling in order to persuade her to carry to term. But it was not considered consistent with the constitution to provide this regulation with justifying grounds. PMID- 17269505 TI - [The pregnant woman's request for caesarean section from a medical point of view]. AB - The wish to be delivered by caesarean section for personal reasons without medical indication must be discussed from both the medical point of view and in view of the legal position of the mother and her child. Today the mortality/lethality risk in primarily indicated and performed caesarean sections is not substantially higher than with vaginal deliveries. What is important is the aspect of the "consequences of caesarean section on following pregnancies". Besides the risk of scar rupture, the drastic increase in the incidence of abnormal placental detachment (placenta accreta/increta/percreta) and placenta praevia in the following pregnancy is of importance. On the other hand, this risk must be weighed against the fetal risk from vaginal delivery in terms of intrauterine death and encephalopathy caused by intrapartum hypoxia as well as cerebral paralysis amounting to 1/500. Pelvic floor damage after vaginal delivery can probably be reduced but not necessarily avoided by primary caesarean section. PMID- 17269506 TI - [Patient-requested caesarean section--a legal perspective]. AB - Some women ask for a caesarean delivery for personal, not medical reasons. Physicians are not obliged to perform an intervention where the medical necessity is lacking. But similar to cosmetic surgery, this intervention is legitimate if there are no health-related contraindications on the part of the mother and if she is able to give her informed consent. The physician has the burden of proof that the patient has been provided with the necessary information on the possible outcomes and risks of the surgical procedure. It is unclear whether statutory health insurance has to pay the costs of this intervention. PMID- 17269507 TI - [Transsexualism from the point of view of sexual medicine]. AB - Transsexualism has been particularly burdened with problems posed by unconfirmed hypotheses about its nosology and epidemiology, even in its history; the application of the Gender Recognition Act (GRA) shows discrepancies and signs of disintegration. The transsexual patient Mr. HH, who was evaluated in Kiel and operated in 1964, had unperturbedly applied to the Federal Constitutional Court, when the Federal Supreme Court could not comply with his desire to be recognized as a female. But the Gender Recognition Act did not become effective until 1981. Because of both inherent and differential diagnostic uncertainties and vaguenesses the German-speaking Sexual Medicine associations in the German speaking countries developed standards for the treatment and evaluation of transsexual persons in 1997 . Due to the lack of objective parameters for transsexualism, the Real-Life Test is indispensable. Weak points in the written law facilitate misuse because of patient insistence resulting in misdiagnoses. PMID- 17269508 TI - [Gender reassignment surgery in transsexualism from a urological perspective]. AB - The surgical treatment of transsexual patients can barely be called satisfactory. Poor quality surgical operations cause the life of the patients so treated to become unhappy. Transsexual surgery should only be performed in centres where a sufficient amount of experience has been gathered, and--what is equally important -an understanding amounting to affinity exists with the problem of transsexualism. There is a great need for better treatment methods. The present situation is far from being optimal. PMID- 17269509 TI - [Gender correction surgery in transsexualism from a legal perspective]. AB - As understood by the German "Transsexuellengesetz" (Gender Recognition Act) transsexualism is to be recognized as a gender identity disorder if a long-term diagnostic-therapeutic process has shown that the transposition of gender roles is irreversible and if, besides psychotherapeutic monitoring, only hormonal and surgical procedures are suitable to relieve the patient's distress related to his gender identity. The German Gender Recognition Act does not contain provisions regarding the diagnosis or medical treatment of transsexualism. Commissioned by the German Sexuality Research Association, the Academy for Sexual Medicine and the Association for Sexology, a committee of experts developed standards for the medical treatment and evaluation of transsexuals. These standards provide a basis and orientational guide for both medical and legal issues. In terms of liability, doctors should carefully consider the recommendations on patient education provided in these guidelines. The costs for hormonal treatment and genital corrective surgery are reimbursed by the Statutory Health Insurances (SHI) if a medical expert confirms that transsexualism is a medical disorder. PMID- 17269510 TI - [Individual healthcare services in the ambulatory sector]. AB - Even in Germany where the majority of the population is insured under the Statutory Health Insurance system (SHI), there is an increasing need for taking more personal responsibility for healthcare services and more private participation in healthcare costs, which is due to continuously stagnating contributions to the German Statutory Health Insurances. "Medical services on individual demand" (IGeL) is the term used to denote a special choice of healthcare services that are available to SHI members, but not reimbursed by the SHI system. Despite the growing demand private healthcare services in the form of "medical services on individual demand" are not generally accepted, neither by all patients nor all physicians. Opponents criticise that "medical services on individual demand" are of less or no benefit to the patients. In 2006, the German Medical Assembly adopted a policy statement including ten basic principles that are intended to help doctors distinguish between useful and unnecessary private healthcare offers, and avoid conflicts with the professional code of conduct. PMID- 17269511 TI - [Extended medical services to the inpatient sector--"medical services on individual demand" in the hospital. General legal conditions, 10 basic rules, and practical examples]. AB - Today, extended medical services--previously known in the context of ambulant healthcare provision or plastic surgery only--are increasingly being offered by hospitals. Hospitals have started to offer these services with good reason: in times of budgetary restraints they want to exploit this emerging new market due to economic necessities and they try to meet rising demands from patients. It is not easy to draw the line between special (extended) medical services and general hospital services. These different categories need to be kept apart, though. Special contracts for these specific extended medical services have to be entered into by hospital and patient in any case where the hospital wants to charge him later on. Different preconditions are to be considered with patients insured by statutory health insurance companies and privately insured patients. The price of extended medical services must be carefully calculated and, in particular, has to be related to the price charged from patients insured via statutory health insurance. Attention should also be paid to other aspects such as taxes, liability law, and hospital subsidisation. The present article presents some basic rules for offering extra medical services in a hospital. PMID- 17269512 TI - [Individual health services without compensation claims from the private health insurances' perspective]. AB - Health insurance should provide medically indicated treatment for everyone. By experience, statutory systems are not able to guarantee these services. Private health insurance offers a wide range of options for securing lasting and solid basic coverage. It is possible to optimize and enlarge this service by providing additional features and reasonable supplements. PMID- 17269513 TI - [Individual medical services with no entitlement to reimbursement: general conditions relating to german social legislation and liability law]. AB - Physicians owe their patients the necessary duty of care in both examination and treatment. A physician who disregards this basic level of care acts negligently and may be held liable for damages. The same level of duty applies to contracting physicians (Sect. 76 para. 4 SGBV). The efficiency principle of Title Five of the German Social Code (SGB V), and in particular the jurisdiction of the Federal Social Court has already taken into account the strained financial situation of the Statutory Health Insurance Systems through increasing rationing elements: Panel patients' entitlement to benefits is limited by the procurement rights of the contracting physician so that actually the two-class medicine strictly denied by politicians has become reality long since. For the physician, a new legal obligation to inform his patient arises from the divergence between the civil and criminal part of the medical statutes on the one hand and the restrictive regulations for physicians practising under SGB V, creating considerable potential for conflict the extent of which will generally remain hidden from the medically ignorant patient. In its decision of December 6, 2005, the Federal Constitutional Court (BVerfG) has set limits to the increasingly restrictive jurisdiction of the Federal Social Court referring to the welfare state principle. The dictate of humanity of Section 70 SGB V must not be degraded to the rank of a mere political statement. PMID- 17269514 TI - Our vulnerable children: poor and overweight. PMID- 17269515 TI - Losing by a nose: diagnostic and therapeutic challenges of the trigeminal trophic syndrome. PMID- 17269516 TI - Sentinel surveillance for Streptococcus pneumoniae antibiotic nonsusceptibility. PMID- 17269517 TI - Pancreatitis after herbal supplement consumption. PMID- 17269518 TI - Chronic renal failure and diabetes mellitus: are they comparable risk factors of coronary artery disease? PMID- 17269519 TI - Correlation between high risk obesity groups and low socioeconomic status in school children. AB - OBJECTIVE: Obesity is a major health problem among children and adolescents which is potentially affected by socioeconomic status (SES). The high risk group (HRG) comprises those youths with a body mass index (BMI) between the 85th and 95th percentile (at risk for overweight) and > or = 95th percentile (overweight). We sought a potential link between the HRG and SES. METHODS: Public schools in Chesterfield County, Virginia measured BMI among students in kindergarten and third, seventh, and tenth grades. We assessed SES based on eligibility for the National School Lunch Program and the percentage of the school-age population living in poverty based on per capita income from the 2000 Census. RESULTS: From 28 to 38% of children and adolescents were in the high risk group. Low SES had robust and highly significant correlations with HRG status with r-values ranging from 0.565 to 0.842, P < 0.0001. CONCLUSIONS: Low SES appears to be an important factor in childhood and adolescent obesity. PMID- 17269521 TI - Is chronic kidney disease comparable to diabetes as a coronary artery disease risk factor? AB - BACKGROUND: Chronic kidney disease (CKD) is one of the known risk factors for coronary heart disease (CHD). Though electrocardiograms (ECGs) have limited accuracy in determining the true prevalence of CHD, we wondered whether CKD and diabetes mellitus (DM) controlled for hypertension (HTN), had similar prevalences of ECG abnormalities that could reflect underlying coronary heart disease. METHOD: Data were collected for 5,942 men and women aged 30 to 69 years in the Tehran Lipid and Glucose Study (TLGS), a crosssectional phase of a large epidemiologic study first initiated in 1999. ECG findings of all subjects were coded according to Minnesota ECG coding criteria. The Whitehall criteria for abnormal ECG findings that could represent ischemia were utilized. Creatinine clearance (Crcl) was estimated using the Cockroft-Gault equation and diabetes was defined according to the American Diabetic Association (ADA) criteria. Subjects with moderate CKD and without DM were compared with the patients with DM without CKD. HTN prevalence was similar. The analysis was performed for all Whitehall ECG ischemia abnormalities combined, and separately for pathologic Q waves. RESULTS: In spite of an overall similar prevalence of smoking, and a lower incidence of dyslipidemia and HTN, moderate CKD patients had a higher prevalence of Whitehall criteria abnormal ECG findings compared with the patients with DM. Over 19% of patients with CKD had abnormal ECG findings while 14.7% of diabetic patients had abnormal ECGs (P = 0.02). The prevalence of Q waves was 11.5% in patients with CKD and 10.8% in patients with DM. In an age-matched subgroup of patients with DM and no CKD, the prevalence of ECG abnormalities was 19.3%, similar to the patients with moderate CKD and no DM (19.7%) (P = 0.9). The prevalence of pathologic Q waves in an age-matched group was 11.45%, compared with 11.5%, respectively. CONCLUSION: Moderate CKD is a major risk factor for the development of the Whitehall ECG criteria which have been associated with ischemic heart disease. The importance of CKD as a risk factor for ECG abnormalities is comparable with DM. Patients with moderate CKD probably are candidates for aggressive CHD risk modification. PMID- 17269520 TI - Statewide sentinel surveillance for antibiotic nonsusceptibility among streptococcus pneumoniae isolates in South Carolina, 2003-2004. AB - BACKGROUND: In 2003, the South Carolina Department of Health and Environmental Control established the Carolina Antibiotic Resistance Surveillance System (CARSS), an active sentinel surveillance system for antibiotic-resistant Streptococcus pneumoniae. METHODS: CARSS includes twelve hospitals. Each hospital was assigned a weighted sample size. Minimum inhibitory concentrations were determined using the E-test method. RESULTS: A total of 452 isolates were collected. The prevalence of penicillin nonsusceptibility in the study was 44.9%. Penicillin intermediate resistance (PCN-I) was 33.2%, and penicillin high-level resistance (PCN-R) was 11.7%. One hundred six (23.5%) isolates were nonsusceptible to one antibiotic. One hundred twenty-four (27.4%) isolates were nonsusceptible to three or more antibiotics. CONCLUSIONS: CARSS confirmed the prevalences of antibiotic nonsusceptibility previously reported for South Carolina. However, CARSS suggests resistance is shifting from PCN-R to PCN-I in South Carolina. There is a high prevalence of multidrug nonsusceptibility in South Carolina. CARSS will continue to monitor these trends. PMID- 17269522 TI - Efficacy of lower dose capecitabine in patients with metastatic breast cancer and factors influencing therapeutic response and outcome. AB - OBJECTIVE: Capecitabine exerts considerable therapeutic efficacy in metastatic breast cancer (MBC) patients previously treated with anthracyclines and taxanes. MATERIALS AND METHODS: In this study, the efficacy and safety of lower dose capecitabine (2000 mg/m(2)/d) in patients with anthracycline- and taxane pretreated MBC were studied with a special emphasis on the potential predictors of time to tumor progression (TTP) and response to the capecitabine treatment. RESULTS: The overall response rate (ORR) was 17%. The median TTP was 5 months. Among various factors analyzed, univariate analysis showed that a performance status (PS) of 2 and the presence of visceral metastases were inversely correlated with TTP. Multivariate analysis showed that a poor PS score was associated with impaired TTP. CONCLUSIONS: Our study indicates that lower dose capecitabine has substantial antitumor activity and a favorable safety profile in the treatment of anthracycline- and taxane-pretreated MBC. Also, only performance score was demonstrated to be a significant parameter affecting TTP. PMID- 17269523 TI - Difficult conversations: anger in the clinician-patient/family relationship. AB - Anger is a "syndrome" of thoughts, feelings and physiologic reactions. Behavioral responses to anger are influenced by multiple contextual factors. Patients and family members may express anger in response to their own experiences of illness, the healthcare system, or the physician-patient/family relationship. Anger may evoke a variety of clinician responses that while understandable, inadvertently escalate patient and family anger. Clinicians who cultivate personal awareness, practice mindful self-monitoring during their interactions, explore the differential diagnosis of anger, demonstrate specific communication skills, set clear boundaries and seek personal support can overcome the challenges of these difficult conversations, and begin to restore trust in the physician-patient/ family relationship. PMID- 17269524 TI - Trigeminal trophic syndrome. AB - Ulceration of the nose may be inadvertently induced by the patient. Although trigeminal trophic syndrome is an uncommon cause of chronic ulcers, healthcare providers should consider the possibility of this disorder when encountering a patient with nasal ulcerations. Trigeminal trophic syndrome most commonly occurs in older women following therapy for trigeminal neuralgia. The ulcers usually involve the nasal ala and paranasal areas. The clinical vignette of a man with a self-induced nasal ulcer secondary to trigeminal trophic syndrome, which was initially suspected to be skin cancer, is presented. Since nasal ulcerations can be secondary to other conditions, a lesional biopsy should be performed to exclude other diagnoses when trigeminal trophic syndrome is entertained. In addition to trigeminal trophic syndrome, the differential diagnosis of conditions that can cause nasal ulcers include factitial disorders with self-induced ulcerations (such as dermatitis artifacta and neurotic excoriations), granulomatous conditions, infectious diseases, malignancy, and pyoderma gangrenosum. Treatment of trigeminal trophic syndrome requires prevention of digital manipulation of the lesion-either by occluding contact with the ulcer, initiating psychotropic medication, or both. Psychiatric and/or pharmacologic intervention should be considered to reduce or resolve further habitual self inflicted injury before surgical intervention. PMID- 17269525 TI - Chronic eosinophilic pneumonia: a review. AB - Chronic eosinophilic pneumonia (CEP) is a disease of unknown cause. The hallmark of CEP is eosinophil accumulation in the lungs. While the triggering factor is unknown, eosinophil accumulation in the lungs is now believed to be secondary to the actions of eosinophil-specific chemoattractants, including eotaxin and regulated upon activation, normal T-cell expressed and secreted (RANTES), and IL 5 released from Th2 lymphocytes in the lungs. There is a female preponderance in CEP, with a peak incidence in the 5th decade; the onset is insidious with weight loss, cough, and dyspnea. An atopic history is common, but asthma is not a prerequisite for the development of CEP. Airways obstruction may develop during the course of CEP, but may also result from CEP. The chest x-ray usually shows bilateral peripheral shadows, which may be migratory. Peripheral eosinophilia is usual. Standard treatment of CEP is with oral steroids, usually with dramatic resolution of symptoms and radiographic changes; however, relapses are common when the daily steroid dose is reduced below 15 mg. Current data suggest that when treatment is stopped, relapse is common in the majority of patients (>80%) followed for a sufficiently long period of time. Some recent reports suggest that treatment with inhaled steroids may be of some value in this condition. PMID- 17269526 TI - Noninfectious complications of peritoneal dialysis. AB - Peritoneal dialysis is an established form of renal replacement therapy. With its increasing popularity, we are now encountering a variety of complications. Noninfectious complications are usually less common as compared with infectious complications. In this review, we discuss some of the common noninfectious complications of peritoneal dialysis such as hernias, hydrothorax, hemoperitoneum, pancreatitis, ischemic colitis and necrotizing enterocolitis, pneumoperitoneum, GERD, subcapsular steatosis and hypokalemia. The awareness of these complications will help in early diagnosis and treatment. PMID- 17269527 TI - Pancreatitis in a woman taking an herbal supplement. AB - A healthy woman developed pancreatitis after starting a popular herbal supplement designed to boost female libido. Following cessation of the herbal supplement, her enzymes quickly normalized. The patient had no risk factors for pancreatitis and anatomic obstruction was later ruled out. The contents of the supplement and their history of side effects are reviewed. As several of the ingredients are estrogenic in nature, this may have contributed to the patient's reaction. Physicians should remember to take a careful history regarding the usage of supplements and alternative medicines. PMID- 17269528 TI - Dysphagia in a HIV patient: concern for the etiology? AB - Dysphagia in human immunodeficiency virus (HIV) patients is most commonly of infectious etiology; however, less common causes of esophageal injury, such as strictures and medication-induced injuries, should be considered in the differential process. We report a case of a 53-year-old man with a 6-year history of HIV on highly active antiretroviral therapy and minocycline, who presented to the emergency room with abrupt onset dysphagia to solids and liquids. He was found to have pill impaction requiring mechanical disimpaction related to an esophageal web and pseudodiverticulosis. In this case description we would like to highlight the importance of noninfectious causes of dysphagia in HIV patients. PMID- 17269529 TI - Malignant pleural mesothelioma with scalp, cerebellar, and finger metastases: a rare case. AB - Malignant pleural mesothelioma (MPM) is a rare and asbestosis-associated tumor. MPM commonly invades locally, mostly in the lung, heart, pericardium, chest wall, and vertebrae. Distant metastasis of MPM is very rare. Here we report a patient with MPM who presented with multiple unusual distant metastases. The patient's thorax tomography demonstrated right-sided, irregularly-thickened pleura with nodular masses and invasion of the chest wall into the subcutaneous area. The patient underwent biopsy for a subcutaneous mass in the right anterior chest wall. Pathologic examination revealed a malignant mesenchymal tumor. During follow-up, he suffered from a painful nodule on the scalp and nodules on the fingers, as well as weakness in his right arm. Cranial magnetic resonance imaging illustrated a 1 cm nodule in the left cerebellar hemisphere. Histopathologic examination of the biopsy from the nodule on the scalp revealed a typical mixed type of MPM, with calretinin, vimentin and creatine 5/6 positivity. Distant metastases can be seen in MPM and a biopsy of metastatic regions can yield the diagnosis. PMID- 17269530 TI - Prosthetic joint infection by Mycobacterium tuberculosis: an unusual case report with literature review. AB - Prosthetic joint infection with Mycobacterium tuberculosis usually involves the hips or knees and can result from either local reactivation, or less often from hematogenous spread. Predisposing conditions include rheumatoid arthritis, chronic steroid use and pulmonary diseases. The most common symptom at presentation is pain, and the most common physical finding is joint swelling and/or a draining sinus tract. The sedimentation rate is helpful when elevated but is nonspecific, and initial skin testing is only helpful when positive. The diagnosis depends on culture and histologic examination of tissue. Removal of the joint combined with oral antituberculous treatment is necessary when the infection is discovered greater than six weeks post joint replacement. Early diagnosis leads to decreased morbidity. Tuberculous infection of prosthetic joints is a rare disease and its diagnosis depends on a high degree of clinical suspicion. PMID- 17269531 TI - Mitochondrial encephalopathy, lactic acidosis and stroke-like syndrome (MELAS): a case report, presentation, and management. AB - Mitochondrial encephalopathy with lactic acidosis and stroke-like syndrome (MELAS) is a progressive neurodegenerative disorder frequently complicated by diabetes mellitus and sensory neuronal hearing loss. This syndrome tends to present initially with stroke-like symptoms. These strokes are nonvascular in nature and are linked to mitochondrial defect such as transient oxidative phosphorylation dysfunction, which in turn results in encephalopathy. The combination of lactic acidosis, multiple nonvascular strokes, encephalopathic psychosis, diabetes, and sensory neuronal hearing loss causes severe dysfunction leading to increased mental disabilities, physical disabilities, and eventually, death. PMID- 17269532 TI - Epinephrine-secreting pheochromocytoma in a normotensive woman with adrenal incidentaloma. AB - Pheochromocytomas are rare neuroendocrine tumors that produce, metabolize, and usually secrete catecholamines. Although hypertension is a common presenting feature of pheochromocytoma, the tumors occur (or are present) in only 0.1% of patients with hypertension. The variability of symptoms and rarity of occurrence render these tumors difficult to diagnose; many are discovered incidentally during radiological examination or at autopsy. A patient is presented with a pheochromocytoma that was discovered incidentally when she presented with abdominal pain and a normal blood pressure. PMID- 17269533 TI - Closure of a nonhealing gastrocutaneous fistula using an endoscopic clip. AB - Gastrocutaneous fistula after gastrostomy tube removal may persist for a prolonged period. We present a case of a 58-year-old woman with a GCF that had persisted for 5 months following the removal of an endoscopically-placed gastrostomy tube (PEG). Conservative therapy with anti-acid medications and administering motility agents was unsuccessful. For the closure of the GCF, the endoscopic metal clips were used to close the fistula. PMID- 17269534 TI - Sickle cell vasoocclusive crisis and acute chest syndrome at term pregnancy. AB - Women with sickle cell anemia are surviving longer and may desire pregnancy. Rare, life-threatening complications of sickle cell anemia, such as acute chest syndrome, may occur at the time of delivery. A 22-year-old woman with sickle cell (HbS/beta+ thalassemia) at 35 weeks of gestation presented with shortness of breath and generalized pain. She was diagnosed with vasoocclusive crisis and acute chest syndrome, managed with exchange transfusion and cesarean delivery, and discharged home with her newborn one week later. Prompt recognition of life threatening complications of sickle cell anemia in a pregnant woman and collaborative medical and obstetric management are essential to optimize maternal and fetal outcome. PMID- 17269535 TI - Evaluation of perinephric, retroperitoneal schwannomas: case report and review of the literature. AB - Schwannomas are tumors arising from the nerve sheath. Because of their infrequent occurrence, nonspecific symptoms, and lack of distinguishing radiologic features, schwannomas are most often diagnosed histologically after surgical excision. We report herein a case of a perinephric, retroperitoneal schwannoma which, after evaluation by computed tomography, magnetic resonance, and angiography, appeared to be a renal cell carcinoma arising from the left kidney. The diagnosis of benign retroperitoneal schwannoma was made by histologic examination and immunohistochemical staining of the excised mass. A practical algorithm for perinephric, retroperitoneal schwannomas is proposed. PMID- 17269536 TI - A case of clinical tetanus in a patient with protective antitetanus antibody level. PMID- 17269537 TI - Clinicians, chaplains and spiritual care. PMID- 17269538 TI - Pre-conceptional folic acid supplementation in uninsured pregnant Hispanic women. PMID- 17269539 TI - Acute myocardial infarction in a 14-year-old male with normal coronary arteries. PMID- 17269540 TI - Patient's page: weight loss and herbal supplements. PMID- 17269541 TI - The tools of a trade: to serve, not to supplant. PMID- 17269542 TI - Who is this patient? PMID- 17269543 TI - Perfecting ourselves: on Christian tradition and enhancement. PMID- 17269544 TI - Gene therapy: human germline genetic modifications--assessing the scientific, socioethical, and religious issues. PMID- 17269545 TI - Gene therapy: science fiction or reality? PMID- 17269546 TI - Sex selection: morality, harm, and the law. PMID- 17269547 TI - Against sex selection. PMID- 17269548 TI - The promise and threat of modern cybernetics. PMID- 17269549 TI - Eye on religion: considering the influence of Buddhist and Shinto thought on contemporary Japanese bioethics. AB - Religious traditions can play a significant role in the shaping of bioethical thought. In Japan, traditional Buddhist and Shinto thought continue to influence contemporary bioethical perspectives. To better define this relationship, this paper examines the correlation between Japanese bioethical perspectives and Buddhist and Shinto thought. An in-depth discussion explores how Buddhist and Shinto scholars have used fundamental concepts with each religious tradition to agree and disagree with the disclosure of an incurable disease to a patient, brain death, and brain-dead organ transplantation. PMID- 17269550 TI - Eye on religion--Shinto and the Japanese attitude toward healing. PMID- 17269551 TI - A case discussion. PMID- 17269552 TI - Selected annotated bibliography on genetic, reproductive and cybernetic technologies. PMID- 17269553 TI - Diacylglycerol acyltransferase: a key mediator of plant triacylglycerol synthesis. AB - Many plants deposit TAG in seeds and fruits as the major form of storage lipid. TAG production is of tremendous socioeconomic value in food, nutraceutical, and industrial applications, and thus numerous conventional and molecular genetic strategies have been explored in attempts to increase TAG content and modify the FA composition of plant seed oils. Much research has focused on the acyl-CoA dependent reaction catalyzed by diacylglycerol acyltransferase (DGAT), which is an integral endoplasmic reticulum protein and has also been shown to be present in oil bodies and plastids. DGAT enzymes exhibit diverse biochemical properties among different plant species, many of which are summarized here. In addition to catalyzing a critical step in TAG biosynthesis, there is evidence that DGAT has roles in lipid metabolism associated with germination and leaf senescence. TAG can also be formed in plants via two different acyl-CoA-independent pathways, catalyzed by phospholipid: diacylglycerol acyltransferase and diacylglycerol transacylase. The current understanding of the terminal step in TAG formation in plants and the development of molecular genetic approaches aimed at altering TAG yield and FA composition of TAG are discussed. PMID- 17269554 TI - Cyclic fluctuations of 3-hydroxy-3-methylglutaryl-CoA reductase in aortic smooth muscle cell cultures. AB - The cyclic fluctuations of HMG-CoA reductase activity and mRNA are reportedly related to feeding the cells in culture or to variations in food consumption by the animals over a 24-h cycle. In this work, we demonstrate cyclic increments in HMG-CoA reductase activity in smooth muscle cells (SMC) not associated with the culture feeding. Since reductase activity also shows a marked rise preceding the S phase, one of the major goals of the present work was to evaluate this dual role of reductase activity and mRNA fluctuations related to the cell cycle and to food intake in the SMC-C/SMC-Ch cultures derived from control-fed (SMC-C) and cholesterol-fed (SMC-Ch) chicks. The period and amplitude oscillations in HMG-CoA reductase activity varied depending on culture conditions: lipoprotein-deficient serum vs. FBS, young vs. senescent cells, or confluent vs. nonconfluent cultures. The HMG-CoA reductase mRNA concentration showed a marked rise after feeding not correlated to the fluctuation activity, suggesting posttranscriptional modulation. Reductase activity and mRNA were down-regulated in SMC-Ch. Since the nutritional culture conditions were the same in both cell lines, these findings indicate that consumption of a high-cholesterol diet by the animals prior to the establishment of the SMC cultures induced changes in the HMG-CoA reductase gene expression in-aortic SMC. PMID- 17269555 TI - Polyunsaturated fatty acids regulate cytokine and prostaglandin E2 production by respiratory cells in response to mast cell mediators. AB - A protective association between breastfeeding and the development of bronchial asthma has been demonstrated. However, a mechanism remains unclear. FA present in human milk but rare in infant formula have been associated with marked immunological modulation as well as some indications of protection from asthma development. We examined the effect of in vitro manipulation of membrane phospholipid on the production of cytokines and prostaglandin (PG)E2 by respiratory epithelial cells (A549) in response to stimulation by mast cell mediators of allergic disease [histamine, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4 and IL-5]. DHA and CLA significantly decreased the production of IL-8 in response to stimulation by TNF-alpha [2907 +/- 970 (DHA) and 6471 +/- 1203 (CLA) vs. 12,287 +/- 2309 (control) pg/mL; P < or = 0.05, mean +/- SEM], whereas both EPA and DHA reduced histamine-stimulated RANTES (regulation on activation, T cell-expressed and -secreted) production [2314 +/- 861 (EPA) and 877 +/- 326 (DHA) vs. 8526 +/- 1118 (control) pg/mL; P < or = 0.03]. PGE2 released in response to histamine was decreased by n-3 [1305 +/- 399 (alpha linolenic acid), 406 +/- 73 (EPA), and 265 +/- 32 (DHA) vs. 9324 +/- 3672 (control) pg/mL; P < or = 0.05] and increased by n-6 [18,843 +/- 4439 (arachidonic acid) vs. 9324 +/- 3672 (control) pg/mL; P = 0.02], with CLA producing a decrease of the same magnitude as DHA [553 +/- 126 (CLA) vs. 9324 +/- 3672 (control) pg/mL; P = 0.03]. This study demonstrates the potential for immunological manipulation of the respiratory epithelium by FA in situ during allergic responses and suggests that further investigation into FA intervention in infants via human milk or supplemented infant formula, to prevent the development of allergic disease, may be worthwhile. PMID- 17269556 TI - Enhanced incorporation of n-3 fatty acids from fish compared with fish oils. AB - This work was undertaken to study the impact of the source of n-3 FA on their incorporation in serum, on blood lipid composition, and on cellular activation. A clinical trial comprising 71 volunteers, divided into five groups, was performed. Three groups were given 400 g smoked salmon (n = 14), cooked salmon (n = 15), or cooked cod (n = 13) per week for 8 wk. A fourth group was given 15 mL/d of cod liver oil (CLO) (n = 15), and a fifth group served as control (n = 14) without supplementation. The serum content of EPA and DHA before and after intervention revealed a higher rise in EPA and DHA in the cooked salmon group (129% rise in EPA and 45% rise in DHA) as compared with CLO (106 and 25%, respectively) despite an intake of EPA and DHA in the CLO group of 3.0 g/d compared with 1.2 g/d in the cooked salmon group. No significant changes were observed in blood lipids, fibrinogen, fibrinolysis, or lipopolysaccharide (LPS)-induced tissue factor (TF) activity, tumor necrosis factor-alpha (TNFalpha), interleukin-8 (IL-8), leukotriene B4 (LTB4), and thromboxane B2 (TxB2) in whole blood. EPA and DHA were negatively correlated with LPS-induced TNFalpha, IL-8, LTB4, TxB2, and TF in whole blood. In conclusion, fish consumption is more effective in increasing serum EPA and DHA than supplementing the diet with fish oil. Since the n-3 FA are predominantly in TAG in fish as well as CLO, it is suggested that the larger uptake from fish than CLO is due to differences in physiochemical structure of the lipids. PMID- 17269557 TI - Dietary fish oil n-3 fatty acids increase regulatory cytokine production and exert anti-inflammatory effects in two murine models of inflammation. AB - The higher incidence of inflammatory diseases in Western countries might be related, in part, to a high consumption of saturated fatty acids and n-6 polyunsaturated fatty acids (PUFA) and an insufficient intake of n-3 fatty acids. The purpose of this study was to examine the effects of dietary n-3 fatty acids on innate and specific immune response and their anti-inflammatory action in models of contact and atopic dermatitis. Balb/C mice were fed for 3 wk either n-6 or n-3 PUFA-fortified diets. After inducing a contact or an atopic dermatitis, immunological parameters were analyzed to evaluate the anti-inflammatory potential of these n-3 PUFA. n-3 PUFA reduced innate and specific immune responses through inhibition of TH1 and TH2 responses, increase of immunomodulatory cytokines such as IL-10, and regulation of gene expression. The inhibition of both kinds of responses was confirmed by the anti-inflammatory effect observed in contact and atopic dermatitis. Reduction in weight, edema, thickness, leukocyte infiltration, and enhancement of antioxidant defenses in the inflamed ears of mice from both models along with the prevention of delayed-type hypersensitivity induced in atopic dermatitis proved n-3 PUFA efficacy. Our data suggest that dietary fish oil-derived n-3 fatty acids have immunomodulatory effects and could be useful in inflammatory disorders. PMID- 17269558 TI - Long-chain n-3 polyunsaturated fatty acid incorporation into human atrium following fish oil supplementation. AB - Recent studies have demonstrated that long-chain n-3 PUFA (LCn-3PUFA) are beneficial in reducing the risk of cardiac arrhythmias. This study was conducted to determine the extent of incorporation of LCn-3PUFA into human atrium following supplementation with a fish oil concentrate high in LCn-3PUFA. Volunteers preparing for coronary bypass surgery were randomized either to the treatment group (n = 8), receiving 6 g/d of fish oil concentrate (4.4 g of LCn-3PUFA), or the placebo group (n = 9), receiving 6 g/d of olive oil for a minimum period of 6 wk. Blood samples were collected prior to commencement of treatment, and preoperatively before bypass surgery. Atrial biopsies were obtained during surgery. The plasma and atrium samples were analyzed by GC following trans methylation to determine FA profile. Post-supplementation, the treatment group had significantly higher plasma levels of 20:5n-3, 22:5n-3, and 22:6n-3 than the placebo group. Analysis of the atrium total lipids revealed a significant increase in the proportion of 20:5n-3 following fish oil supplementation. There was no significant difference in the concentration of 22:5n-3 and 22:6n-3 in the atrium total lipids; however, an upward trend was observed in subjects receiving fish oil supplementation. In the phospholipid fraction of the atrium, both 20:5n 3 and 22:6n-3 increased, whereas 20:4n-6 levels decreased. This study demonstrates for the first time that short-term supplementation with fish oil concentrate results in significant incorporation of LCn-3PUFA with a concomitant depletion of the eicosanoid substrate (20:4n-6) in the human atrium. PMID- 17269559 TI - Chlorinated fatty acids in lipid class fractions from cardiac and skeletal muscle of Chinook salmon. AB - Analysis of chlorinated fatty acids (CFA) in tissues can be difficult because of their low concentrations. This task becomes even more difficult when samples are from organisms living in remote locations with very little exposure to environmental contamination. Therefore, enrichment of CFA is necessary prior to analysis. In this study, CFA were enriched from fractionated lipid classes of cardiac and skeletal muscle of Chinook salmon (Oncorhynchus tshawytscha) to determine CFA distribution among lipid classes and tissue types and to demonstrate the sensitivity of this method to detect CFA at trace concentrations. The lipids extracted from cardiac and skeletal muscle of O. tshawytscha were separated into fractions containing TAG, FFA, and phospholipids. After transesterification, the FAME derivatives from each lipid class were analyzed by GC with a halogen-selective detector (XSD) to determine the concentrations of dichlorostearic acid and dichloropalmitic acid. Other chlorinated compounds detected by GC-XSD were analyzed by GC-MS. CFA were observed in all lipid classes in both cardiac and skeletal muscle tissues. However, the highest concentrations of CFA were found in the phospholipids of both tissue types, about 1-2 mg/g lipid. It was also shown that dichloropalmitic acid concentrated in cardiac phospholipids whereas dichlorostearic acid was found primarily in the phospholipids of skeletal tissue. CFA concentrations in TAG and FFA fractions were below 150 mg/g lipid. This study demonstrates a small-scale approach to the study of CFA at trace concentrations and their distribution among lipid classes. PMID- 17269561 TI - Collins on current issues: diversity challenges in nursing care and management. PMID- 17269560 TI - Effects of flaxseed derivatives in experimental polycystic kidney disease vary with animal gender. AB - Flaxseed derivatives, including both oil and flax lignan, modify progression of renal injury in animal models, including Han:SPRD-cy polycystic kidney disease (PKD). Gender is a significant factor in the rates of progression of many forms of human renal disease, but the role of gender in the response to nutrition intervention in renal disease is unexplored. In this study, male and female Han:SPRD-cy rats or normal littermates were fed either corn oil (CO) or flax oil (FO) diets, with or without 20 mg/kg of the diet flax lignan secoisolaricinoresinol dyglycoside (SDG). Renal injury was assessed morphometrically and biochemically. Renal and hepatic PUFA composition was assessed by GC and renal PGE2 release by ELISA. FO preserved body weight in PKD males, with no effect in females. SDG reduced weight in both normal and PKD females. FO reduced proteinuria in both male and female PKD. FO reduced cystic change and renal inflammation in PKD males but reduced cystic change, fibrosis, renal inflammation, tissue lipid peroxides, and epithelial proliferation in PKD females. SDG reduced renal inflammation in all animals and lipid peroxides in PKD females. A strong interaction between SDG and FO was observed in renal FA composition of female kidneys only, suggesting increased conversion of C18 PUFA to C20 PUFA. FO reduced renal release of PGE2 in both genders. Gender influences the effects of flaxseed derivatives in Han:SPRD-cy rats. Gender-based responses to environmental factors, such as dietary lipid sources and micronutrients, may contribute to gender-based differences in disease progression rates. PMID- 17269563 TI - Increasing the diversity of nursing students for future improved national health outcomes and reduced health disparities: one nursing program's efforts to meet goals of the Sullivan Commission report. PMID- 17269564 TI - Cultural competence at the bedside. PMID- 17269565 TI - Hospital diversity initiative for new access students: NETS, A career ladder program. PMID- 17269566 TI - Study shows majority of nurses rely on evidence-based practice. PMID- 17269567 TI - Nurses can help recovering persons stay sober during the holiday season. PMID- 17269568 TI - Mixed generations in the workplace. PMID- 17269569 TI - Drug-resistant 'superbugs' require more aggressive measures. PMID- 17269570 TI - Finding the right balance for contract reviews. AB - Contracts are the crux of a materials manager's job. Vendors and hospitals alike use them to protect their interests. But contracts are only advantageous to hospitals when the materials manager understands contractual language and/or knows when to seek legal counsel. Regardless of whether your legal counsel is in house or outsourced, it is important to establish and maintain a solid working relationship. Otherwise, contracts can become mired in red tape or the language essential to success could be incorrect or insufficient. PMID- 17269571 TI - Technological methods used to prevent errors aren't infallible. AB - Though technology has helped significantly to improve medication safety, the fact remains that human interaction still plays a role. Overcoming human error takes vigilance and a commitment from everyone on a hospital's staff. Through the implementation and use of proper protocols for everything from infusion pumps to pharmacy computer systems, a safer environment can be created for patients. Another means of mitigating human error is to ensure that health care workers are properly trained on all new technological systems. PMID- 17269572 TI - Consignment trays and the hidden costs of sterilization. AB - Consignment implant trays are often an overlooked facet of the supply chain. If not handled properly, they can cost a hospital thousands of dollars in delivery charges as well as potentially decreasing the level of patient safety. It is critical that value analysis committees have input from central service and that time is taken to consider logistics before signing agreements, especially with regard to proper sterilization instructions and delivery method. If trays arrive too late, it is more likely that corners will be cut with the sterilization process. PMID- 17269573 TI - Linking materials to the revenue cycle. PMID- 17269574 TI - Involving staff in product evaluations is essential for successful operations. PMID- 17269575 TI - Flu season and the threat of a pandemic. PMID- 17269576 TI - Medicare Advantage contracting--be watchful now and ready for the future. PMID- 17269577 TI - Managing critical test results. PMID- 17269578 TI - Global health in today's medical education. PMID- 17269579 TI - Promoting safe drinking water. AB - Ensuring access to safe drinking water is a major public health concern. The outbreaks of disease from water-borne pathogens in communities like Walkerton and North Battleford alerted the federal government to the need for a standardized multi-barrier approach to managing public drinking water distribution systems. Although many provinces and territories have adopted such an approach, there are problems with water quality throughout Canada. Between 1997 and 2004, the authors conducted a community health needs and resources assessment study in Newfoundland and Labrador to assess health beliefs and practices, satisfaction with health and community services and concerns in relation to community health. The data collection methods used were a random household survey (N = 2,842), key informant interviews (N = 86) and focus group sessions (N = 22). The results indicated that the quality of drinking water was of serious concern. In this article, the authors discuss the study findings and the implications for nursing practice in relation to developing healthy public policy and population health initiatives. PMID- 17269580 TI - Promoting environmentally responsible health care. AB - Dioxins, polyvinyl chloride and di(2-ethylhexyl) phthalate are the three main toxins interfering with the goal to maintain a healthy environment, according to the international organization Health Care Without Harm (2004). Exposure to these chemicals has been linked to cancer, as well as reproductive, cardiac, hepatic and developmental disorders (Tickner, Schettler, Guidotti, McCally, and Rossi, 2001). Health-care clients are potentially exposed to these toxins every day: polyvinyl chloride equipment, such as i.v. bags and tubing, is widely used in hospitals, and medical incineration practices emit dioxins into the air (Chlorine Chemistry Council, 2006). Nurses are uniquely positioned to play an active role in environmentally responsible health care through education, advocacy and the implementation of measures to reduce medical wastage and exposure to these chemical toxins (Canadian Nurses Association, 2005). PMID- 17269581 TI - Tackling public health--at home and abroad--is a labour of love. Interview by Alicia Priest. PMID- 17269582 TI - Integrating mental health into urgent care in a community health centre. AB - Competent, convenient mental health assessment and psychosocial intervention are seldom delivered in the right place, at the right time and by the right person. One solution to this problem is to have mental health services integrated into urgent care in a community health centre. Unfortunately, although there is literature on urgent care centres, mental health centres and psychiatric emergency rooms, there is scant information about the integration of mental health services into an urgent care centre. PMID- 17269583 TI - Passion for nursing rekindled. PMID- 17269584 TI - Public health infrastructure needs investment. PMID- 17269585 TI - Is raloxifene ready to be used for prevention of breast cancer? PMID- 17269586 TI - Breast cancer risk in flight attendants: an update. AB - Although further research is required, epidemiological evidence indicates that breast cancer risk is increased by 40% among flight attendants. Female flight attendants and women who fly frequently should be informed of this potential increase in risk and be encouraged to participate in appropriate breast cancer screening programs. PMID- 17269587 TI - Human breast milk immunology: a review. AB - Breast feeding has been shown to enhance the development of the immune system of the newborn as well as provide protection against enteric and respiratory infections. It has been suggested that implementation of breast feeding programs has the potential to save hundreds of thousands of lives worldwide. Human milk is a bodily fluid which, apart from being an excellent nutritional source for the growing infant, also contains a variety of immune components such as antibodies, growth factors, cytokines, antimicrobial compounds, and specific immune cells. These help to support the immature immune system of the newborn baby, and protect it against infectious risks during the postnatal period while its own immune system matures. This article reviews some of the factors in human breast milk that give it these important properties. PMID- 17269588 TI - HER2 status in bilateral breast cancer. AB - BACKGROUND: The purpose of this study was to identify correlates of HER2 status for patients with bilateral breast cancer. METHODS: Data were collected prospectively in our institutional review board approved patient registry for all patients with asynchronous (ABBC) and synchronous (SBBC) bilateral infiltrating breast cancer whose HER2 assays were performed at our laboratory using FISH. Data were analyzed using the Wilcoxon rank sum and Chi-square test. RESULTS: Data were available for 98 tumors in 49 patients. Patients diagnosed with SBBC were more likely to be white (P = 0.023); to have bilateral HER2 non-amplified tumors (P = 0.022) and to be older at diagnosis (P = 0.025) compared to those with ABBC. Patients with one HER2 amplified tumor were likely to have at least one tumor be hormone receptor negative and to have ABBC. CONCLUSIONS: Only 16% of patients in this study had one tumor that was HER2 amplified; no patient had bilateral HER2 amplified tumors. PMID- 17269589 TI - Application of a locally placed anesthesia catheter for reduction of postoperative pain after mastectomy for breast cancer. AB - OBJECTIVE: Postoperative pain management is important, especially in cancer patients. We describe our experience with the application of a locally placed continuous local anesthetic-releasing catheter for wound pain reduction after mastectomy for breast cancer. MATERIALS AND METHODS: Retrospective evaluation of a continuous series of 41 patients at Fayette Medical Center, AL, USA, receiving an anesthetic-releasing catheter from January 2000 until June 2004. We used a pain management system with 270 ml volume of 0.25% Sensorcaine (bupivacaine and epinephrine) and a release rate through dual catheter ends of 2 ml/h each, lasting for approx. 67.5 h post op. RESULTS: 41 patients, age 67.0 (42-84) years, height 164.5 (152.4-177.8) cm, weight 71.1 (45.4-129.4) kg were treated after mastectomies (n=43; two bilateral) for breast cancer (n=30) and carcinoma in situ (CIS) (n= 11) with a local anesthetic wound catheter (n=43). The following procedures were performed: 31 modified radical mastectomies, 10 simple mastectomies and 2 simple mastectomies with sentinel lymph nodes. Intraoperative application of such a catheter system took less than 3 minutes. No intra- or postoperative complication or infection occurred within a follow up time of 30.3 months (0.2-52.4). CONCLUSION: Application of this temporary anesthesia catheter after mastectomy is easy and safe and reduces postoperative pain. PMID- 17269590 TI - Is it safe to preserve the nipple areola complex during skin-sparing mastectomy for breast cancer? AB - Skin-sparing mastectomy (SSM) with nipple areola complex (NAC) preservation appears to be oncologically safe, provided the tumor is not close to the nipple and a frozen section protocol for the retroareolar tissue is followed. PMID- 17269591 TI - The current management of gynecomastia: an update. AB - Gynecomastia is a common condition characterized by a benign proliferation of the glandular component of the male breast. It is thought to be due to an increase in the ratio of estrogen to androgen activity. The present article reviews the pathogenesis, clinical features, and contemporary treatment of gynecomastia. PMID- 17269592 TI - Renal-coloboma syndrome: a single nucleotide deletion in the PAX2 gene at Exon 8 is associated with a highly variable phenotype. AB - BACKGROUND: Renal-coloboma syndrome (RCS) is an autosomal dominant disorder characterized by renal abnormalities and optic nerve defects, caused by heterozygous mutations of the PAX2 gene. This gene encodes for the PAX2 developmental nuclear transcription factor, which is primarily expressed during embryogenesis in kidneys, eyes, ears and in the central nervous system. The aim of the present study was to characterize PAX2 mutations in a renal coloboma syndrome family with a highly variable phenotype. METHODS: DNA screening was performed by direct sequencing. RESULTS: Five subjects over three generations presented with renal hypodysplasia or horseshoe kidneys in association with bilateral optic nerve colobomas in four cases, one patient with early-onset renal failure had no detectable eye defects. All five subjects carried a novel PAX2 mutation consisting in a frameshift mutation located in Exon 8 (G91 I del), which causes premature termination of translation and loss of the PAX2 transactivation domain. CONCLUSION: This is the first report of a PAX2 mutation located in Exon 8. The variability of clinical symptoms may be explained by the limited disruption of the protein sequence at the transactivation domain. PMID- 17269593 TI - Favorable long-term outcome of nephrotic syndrome after allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: The development of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (HS-CT) is a rare complication with few long-term outcome data. PATIENTS: Clinical course and long-term outcome of three adult patients and one child with NS after HSCT (total number of transplants n = 533) are presented. RESULTS: The median age at onset of NS was 35 years (range 15 - 56), occurring at a median of 17 months (range 11 - 21) after HSCT. Discontinuation of cyclosporine A (CSA) prior to onset of NS was a consistent feature and occurred a median of 6 months (range 2 - 10 months) prior to the development of NS. The histopathological lesion was membranous nephropathy (n = 3) and membranoproliferative glomerulonephritis Type 1 (n = 1). History of acute or concomitant clinically apparent chronic graft versus host disease (GVHD) was present in all cases except the pediatric patient who had abundant DR-activated cytotoxic T cells without evidence of viral reactivation. Long-term immunosuppression for 11 - 36 months with steroids (n = 1), combined steroids and CSA (n = 2) or CSA alone in steroid-refractory NS (n = 1) resulted in sustained remission of the NS in all patients (12 months - 8 years off immunosuppression). CONCLUSION: NS after HSCT seems to be etiologically related to subclinical or overt chronic GVHD, which flares up after discontinuation of CSA. However, resumption of immunosuppression can reverse NS as well as GVHD and induce favorable sustained long-term remission. PMID- 17269594 TI - Prospective comparison of the effects of maxacalcitol and calcitriol in chronic hemodialysis patients with secondary hyperparathyroidism: a multicenter, randomized crossover study. AB - BACKGROUND: Maxacalcitol is a vitamin D analogue, which is administered intravenously for secondary hyperparathyroidism in dialysis patients as well as calcitriol. However, few dose-comparison clinical studies have been reported for these drugs. The present multicenter, randomized crossover study was conducted to determine the equivalence of maxacalcitol and calcitriol doses. METHODS: Subjects comprised 31 patients on chronic hemodialysis with secondary hyperparathyroidism who had not received maxacalcitol or calcitriol in the previous 3 months. Patients were randomly divided into two groups, and maxacalcitol or calcitriol was administered in a crossover design for 12 weeks each. Maxacalcitol and calcitriol doses were adjusted based on serum levels of calcium and intact parathyroid hormone. RESULTS: After the 12-week maxacalcitol/calcitriol administration, there were no significant differences in levels of calcium (maxacalcitol 2.40+/-0.22 mmol/1 (9.6+/-0.9 mg/dl), calcitriol 2.42 + 0.25 mmol/l (9.7+/-1.0 mg/dl), p = 0.71), phosphate (maxacalcitol 1.97 + 0.42 mmol/l (6.1+/ 1.3 mg/dl), calcitriol 2.00+/-0.48 mmol/l (6.2+/-1.5 mg/dl), p = 0.64), intact parathyroid hormone (maxacalcitol 267+/-169 pg/ml, calcitriol 343+/-195 pg/ml, p = 0.11) in serum or other bone-metabolic parameters such as serum alkaline phosphatase. The doses ofmaxacalcitol and calcitriol were 49.3+/-23.7 microg/month and 9.0+/-3.8 microg/month, respectively, and maxacalcitol : calcitriol dose ratio was 5.5: 1. No severe adverse reactions were seen for either maxacalcitol or calcitriol during the study period. CONCLUSIONS: Comparable therapeutic efficacy can be obtained in the treatment of secondary hyperparathyroidism using either maxacalcitol or calcitriol at a dose ratio of 5.5 : 1. PMID- 17269595 TI - Low-calcium dialysate improves mineral metabolism in hemodialysis patients. AB - BACKGROUND: The Kidney Disease Outcomes Quality Initiative (K/DOQI) Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease recommend 1.25 mmol/l Ca dialysate for both hemodialysis and peritoneal dialysis, while 1.5 mmol/l Ca dialysate has been used in our dialysis center. METHODS: Therefore, we switched the dialysate calcium concentration from 1.5 - 1.25 mmol/l and observed the effects on serum calcium (S-Ca), phosphorus (S-P), 1-84 parathyroid hormone (whole PTH, w-PTH), bone-specific alkaline phosphatase (BAP), and tartrate resistant acid phosphatase isoform 5b (TRACP-5b) for 6 months in 58 hemodialysis patients. Prescription of active vitamin D (VD) metabolites and Ca carbonate was increased in response to the changes in laboratory data. RESULTS: Decrease of S Ca was evident at 2 weeks and S-Ca remained low for 6 months. Transient elevation of S-P, which might be caused by stimulated bone resorption, was observed after the switch. In patients with low PTH (w-PTH less than 90 pg/ml before the switch), continuous increase of w-PTH, BAP, and TRACP-5b was observed. This appeared to be a favorable response because the risk ofadynamic bone disease was high in this group of patients. On the other hand, acute elevation of the 3 parameters was well-controlled in patients with moderate and high PTH (w-PTH from 90 - 180 pg/ml, w-PTH more than 180 pg/ml, respectively) by increased dosage of active VD. CONCLUSION: These results demonstrate that 1.25 mmol/l Ca dialysate improved mineral metabolism by lowering S-Ca and releasing oversuppression of PTH. Our data also suggest that appropriate use of active VD could prevent acute rise of PTH. PMID- 17269596 TI - Acute effects of hemodialysis on salivary flow rate and composition. AB - AIMS: To evaluate acute effects of hemodialysis (HD) on the salivary flow rate, pH and biochemical composition before, during and after completion of a dialysis session. MATERIAL AND METHODS: Unstimulated whole saliva (UWS) and chewing stimulated whole saliva (CH-SWS) were collected in 94 HD patients. Salivary flow rate, pH, concentrations of total protein, albumin, cystatin C, secretory immunoglobulin A (S-IgA) and of sodium, potassium and urea were measured. RESULTS: HD had an acute stimulating effect on the salivary flow rate (UWSbefore = 0.30+/-0.22 ml/min, UWSduring = 0.39+/-0.25 ml/min, p < 0.005). The mean pH of UWS showed a small but significant increase during HD mainly due to an increased watery secretion from the salivary glands. The salivary biochemical constituents changed markedly, but no significant difference in output was found. The electrolyte concentration did not change significantly during dialysis. The level of urea in CH-SWS declined to 40% (Ureabefore = 25.+/-6.4 mmol/l, Ureaduring = 15.3+/-4.5 mmol/1). CONCLUSIONS: This study shows that HD has significant acute effects on both salivary secretion rate and protein concentrations in saliva. We conclude that the observed changes in salivary concentrations and proteins are mainly due to an increased watery secretion from the salivary glands. PMID- 17269597 TI - Idiopathic nodular glomerulosclerosis: three Japanese cases and review of the literature. AB - Idiopathic nodular glomerulosclerosis (ING) is characterized as diffuse nodular glomerulosclerotic lesions, closely resembling Kimmelstiel-Wilson lesions without diabetic mellitus. We report here three Japanese cases of ING and discuss the previous reports. The patients were 75-, 48- and 84-year-old males with a history of long-term hypertension. Laboratory examination revealed moderate proteinuria and mild renal dysfunction. Diabetes mellitus was excluded by repeated clinical and laboratory investigations. Renal histology revealed nodular glomerulosclerosis, and both afferent and efferent arteriolosclerosis in all patients. In electron microscopy, the glomerular basement membrane was markedly thick in all patients. A low-protein diet and potent anti-hypertensive treatment using angiotensin-converting enzyme inhibitors were initiated in all patients and urinary protein excretion significantly reduced without the progression of renal dysfunction. We reviewed 42 previously reported cases and our three cases. The analysis revealed that common clinical features of ING are being male (82.2%) of relatively advanced age (mean age 61.3 years), with hypertension (82.2%), mild renal dysfunction (mean serum creatinine 2.9 mg/dl) and moderate urinary protein excretion (mean 4.05 g/day). Common histopathological findings of ING are nodular glomerulosclerosis (100%), arterio-arteriolosclerosis (91.2 and 89.7%) and glomerular basement membrane thickening (85.7%). In conclusion, ING is one of the phenotypes of arteriosclerotic renal disease without diabetes mellitus. Severe arterio-arteriolosclerosis may contribute to the progression to glomerular nodular formation in ING. The combination of renin-angiotensin system inhibition and a low protein diet can be beneficial for the reduction of urinary protein excretion. PMID- 17269598 TI - Rheumatoid arthritis-induced pseudotumoral AA amyloidosis of the bladder with vesico-peritoneal fistula. AB - Rheumatoid arthritis-induced AA amyloidosis of the bladder is rare, with fewer than 25 cases reported so far. This localization may be life-threatening with a mortality rate of about 60%, most often due to massive hematuria or multiorgan failure as a result of systemic amyloidosis. We report the case of a 72-year-old woman with a long history of rheumatoid arthritis who developed gross hematuria that induced severe anemia. Ultrasonography and tomodensitometry revealed a large mass localized in the upper part of the bladder. Cystoscopy showed a congestive inflammatory area with a large vesicoperitoneal fistula. Biopsies revealed amyloidosis, and immunohistochemical staining of the specimens defined the process as AA amyloidosis. The amyloid deposits were also found in the rectum, duodenum, uterus and kidneys. This case of rheumatoid arthritis-induced AA amyloidosis of the bladder is characterized by its pseudotumoral aspect and the existence ofa vesico-peritoneal fistula: only 2 cases have been reported so far. Treatment was symptomatic, and the patient died from cachexia. The pseudotumoral forms of AA amyloidosis, including amyloidosis of the bladder, deserve an early correct diagnosis. Otherwise, an incorrect diagnosis, especially cancer, may prompt inappropriate treatments. PMID- 17269599 TI - Renal complications in two patients with dentatorubral-pallidoluysian atrophy. AB - Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by various combinations of myoclonus epilepsy, ataxia, choreoathetosis and dementia. No specific therapy has been established and renal complication is rare. We report two cases of DRPLA with renal complications. Hematuria and proteinuria had gradually progressed for 2 and 13 years in these patients. Renal biopsy findings revealed focal glomerulosclerosis in one case and end-stage kidney disease in the other case. Angiotensin-converting enzyme inhibitor and angiotensin receptor II antagonist were administered to both patients, resulting in improved proteinuria and preserved renal function in one patient, while renal function continued to deteriorate in the other patient. Although renal complication is rare in patients with DRPLA, the presence of renal disease has to be suspected in patients with persistent proteinuria. PMID- 17269600 TI - Smoking, polyuria and impaired vision. AB - The pituitary gland can be involved in a variety of medical conditions, including metastatic tumors. Metastases to the pituitary gland, although absolutely rare, more commonly affect the posterior pituitary lobe and so frequently present with diabetes insipidus. We report on a 48-year-old male heavy smoker patient suffering from sudden onset of polyuria and persistent thirst. Laboratory results revealed central diabetes insipidus. Computed tomography (CT) scan of the brain showed a mass located in the sella turcica and in the suprasellar region. CT scan of the chest showed a mass in the right superior lobe with mediastinal lymphadenopathy, with bronchoscopy and biopsy features of pulmonary adenocarcinoma. The patient received radiotherapy on the pituitary gland and adjuvant chemotherapy, and as intrasellar and suprasellar mass decreased in size, urinary output was accordingly reduced. Therefore, is that in patients with risk factors for cancer and sudden onset of diabetes insipidus pituitary metastasis should be taken into account in differential diagnosis. PMID- 17269601 TI - Acute renal infarction in a patient with left atrial myxoma. AB - A 24-year-old male first attended our hospital with acute onset of right flank pain radiating to the right lower quadrant of the abdomen. A contrast-enhanced computer tomography (CT) scan showed renal infarction, and he was admitted immediately for treatment. On admission, the right lower abdominal pain diminished gradually. On the second day in hospital, a left atrial echogenic mass was detected which filled the left atrial cavity; it appeared to be a left atrial myxoma measuring 3.9+/-4.9 cm. The patient was immediately transferred and underwent emergency surgery. Histologic examination confirmed the diagnosis of myxoma. Post-operatively, he recovered well and was discharged from hospital without any further specific treatment. PMID- 17269602 TI - Heart and renal failure in renovascular hypertension caused by giant cell arteritis--case report. AB - We report a case of a male teenager with severe heart and acute renal failure as the dominant clinical manifestations of renovascular hypertension (RVH) caused by atypical giant cell arteritis (GCA). Unrecognized RVH and treatment of the consequent heart failure by angiotensin-converting enzyme inhibitors (ACEI) probably contributed to progression of renovascular disease to bilateral renal artery occlusion. Recurrent "flash" pulmonary edemas could not be prevented until surgical revascularization of the only functioning right kidney was achieved by an aortorenal bypass. Prompt post-operative normalization of heart function and arterial hypertension occurred despite the histopathological finding of the resected renal artery compatible with GCA and 4-year duration of significant renovascular disease. At the last check-up, the patient was asymptomatic, with normal arterial pressure on the prescribed treatment: carvedilol, hydrochlorothiazide, prednisolone 20 mg daily and aspirin. Subsequent follow-up is necessary to observe the evolution of GCA as an exceptionally rare cause of RVH. PMID- 17269603 TI - Lupus nephritis after hepatitis B vaccination: an uncommon complication. PMID- 17269605 TI - [Radiography in this journal]. PMID- 17269604 TI - Isoniazid induced acute bilateral cerebellar syndrome in chronic kidney disease. PMID- 17269606 TI - [Integration of health promotion in the field of nursing]. AB - Health promotion is one of many strategies deployed by nurses. Documents and field experience suggest a partial integration of such interventions. A detailed analysis of available literature shows that such an assertion might be premature for three reasons: 1) the integration of health promotion in nursing has been the subject of only a limited number of empirical studies, 2) definitions of health promotion developed through nursing are some of the most frequently quoted and 3) elements of contemporary discourse are often enclosed in these definitions. The discussion examines the gap between the discourse and the practice of health promotion. This analysis concludes to a pluralism of paradigms in nursing; a situation due to the width of the grounds covered by the discipline. Recommendations and stakes are addressed. PMID- 17269607 TI - [Concept of competence with regard to the evolution of work: definition and perspectives]. PMID- 17269608 TI - [Evaluation methods in the formation of nursing and professional competence]. PMID- 17269609 TI - [Patient competence]. PMID- 17269610 TI - ["Interactional competence (in nursing)]. PMID- 17269611 TI - [From caring practices to nursing sciences]. AB - Summary of the thesis: Nurse training was born in the 1870's spurred on by doctors from the Red Cross and in the state-owned hospitals of Paris. Leonie Chaptal played a fundamental role in the elaboration of the first curriculum, a curriculum based on the knowledge which is useful for the nurse to assist the doctor. However, school based in France from Florence Nightingale's trend emphasize the professional autonomy of the nurse. Nursing training and profession therefore evolve in an ambivalence which leads to develop either "caring techniques" close to medical techniques, or a financial autonomy claimed by the "appropriate role" and the nursing clinical approach. Today the nursing profession finds itself in the heart of reforms: transfer of competence, validation of the acquired knowledge from experience, reform of the curriculum with a possible connection with the university. Having defined the criteria of the science by taking example on the model of the sciences of education, the study of nursing research published in the ARSI from 1985 in 2005 shows that nursing research exits and gives a general idea of investigated subjects, often referred to human sciences; hence a first approach of reference sciences, on which nursing sciences can establish and develop, knowing that the title nursing sciences is only used in Quebec. PMID- 17269612 TI - [Are we realistic about nursing research in nursing schools?]. AB - Education in nursing research in nursing schools in Switzerland has been in existence for many years but has had little impact on professional practice. This kind of education does not meet the needs of the students and the profession. Education in nursing research must be adapted, must address epistemological questions and must be integrated into the entire training programme and not only be offered at the end of the education. It could be summarised in five dimensions: 1) professional teaching founded on research results; 2) the regular reading of research papers; 3) meetings with researchers; 4) teaching of research methodology adapted to the field; and 5) a dissertation adapted to the field and considering the conditions of students' research. PMID- 17269613 TI - [Nursing and resuscitation: a specialty?]. PMID- 17269614 TI - Sensitivity and specificity of prostate-specific antigen for prostate cancer detection with high rates of biopsy verification. AB - In this article we explain findings from the Prostate Cancer Prevention Trial (PCPT) concerning the operating characteristics of PSA for biopsy-detectable prostate cancer, with special emphasis on a subpopulation of men with PSA less than 4 ng/ml, what is often regarded as the "normal" level of PSA in healthy men. The PCPT enrolled 18,882 healthy men 55 years of age or older, with a PSA value less than 3 ng/mL and a normal digital rectal exam (DRE); 9,459 of these men were randomized to the placebo arm and 9,423 to the finasteride arm In this report we summarize the operating characteristics of PSA only for the placebo arm of the PCPT; operating characteristics of PSA on the finasteride arm are more complicated to assess since finasteride approximately halves the PSA value and will be reported only briefly. In our first analysis, we focused on a group of 2,950 men on the placebo arm who had had an end-of-study biopsy and a normal DRE and PSA < 4 ng/mL for all 7 years of the study. For prostate cancer, the standard PSA cut-off of 4 ng/mL has low sensitivity: with this cut-off only 20.5% of the prostate cancer cases test positive-nearly 80% of prostate cancer cases are missed. The specificity at this cut-off is high (93.6%) meaning only 6.2% of men who do not have prostate cancer falsely test positive. Lowering the PSA threshold for screening increases detection of aggressive cancer at an earlier stage, but has the unavoidable tradeoff of increased detection of the biologically irrelevant cancers. PMID- 17269615 TI - Adhesion molecules expression as a potential marker of prostate cancer aggressivity. A TMA study of radical prostatectomy specimens. AB - Adhesion molecule disorders may be important in different cell control pathways, and consequently in neoplastic cell disorders. This paper will consider only some of the aspects of intercellular relationship. The main anchoring molecule of these two structures is E-cadherin, which is bound to a molecule complex (catenins and vinculin) that connects it to the actin of the cytoplasmatic cytoskeleton. This adhesion molecule complex maintains cell adhesion but it is also involved in differentiation phenomena and may be pathways of action of different growth factors. When we study the expression of E-cadherin according to the Gleason pattern, we verify progressive loss of the adhesion molecule as the Gleason grade increases (abnormal in 35% of Gleason < 7 score versus 75% in cases of Gleason > 7 score). This correlation reinforces the idea of using the expression of adhesion molecules as a prognostic factor. Considering the great interrelation between the various cell-cycle regulating systems, it is probable that an approach to this interweaving through regulation and de-regulation of the adhesion molecule expression may turn out to be one of the most useful pathways in the future. PMID- 17269616 TI - HER-2 expression and gene amplification in high-grade PIN and prostate cancer. AB - The aim of the current study was to analyze HER-2 expression and gene amplification in prostate cancer and HGPIN incidentally detected in cystoprostatectomies. Eighty prostate cases were used. Group 1 (incidental): nineteen cystoprostatectomy specimens with prostate cancer and HGPIN and no residual urothelial carcinoma in the prostate. Group 2 (untreated): twenty-five radical prostatectomy specimens with prostate cancer Group 3 (hormonally treated): nineteen radical prostatectomy specimens with prostate cancer. All the patients were under total androgen ablation therapy for three months before surgery. Group 4 (hormone-independent): nine TURP specimens with locally recurrent androgen independent prostate cancer Group 5 (normal reference): eight cystoprostatectomy specimens without HGPIN and without prostate cancer, and no residual urothelial carcinoma. None of the patients belonging to Groups 1, 2, and 5 had received chemotherapy, hormone therapy, or radiation therapy before surgery. Weak to moderate HER-2 membrane immunoreactivity was observed in most of the basal cells but not in the secretory cells of normal prostatic ducts and acini both in the cystoprostatectomies and in the radicals of the untreated patients. High-grade PIN. HER-2 overexpression was present in the secretory cells in 26% of HGPIN cases in the CyP group, 40% in the untreated clinically detected cancer group, and 83% in the treated group. Prostate cancer HER-2 overexpression was seen in 16% of cases in the CyP group, 36% in the untreated group and 47.5% in the treated group. HER-2 overexpression was present in 78% of cases with androgen independent PCa. Association of HER-2 overexpression and gene amplification. When considering HGPIN the lowest proportion of cases with HER-2 overexpression and with nuclei with gene amplification was seen in the CyP specimens (7%), whereas the highest was in the treated material (28%). As far as the cancers were concerned, the proportions were slightly higher than in HGPIN, the lowest value being in the CyP specimens (9%) and the highest in the hormone independent PCa (62.5%). A statistically significant difference in the number of cases with both overexpression and amplification was only seen between CyP and hormone-independent cancers (p = 0.007). PMID- 17269617 TI - Pathological aspects of prostate cancer aggressive behavior. Personal experience in differentiating data. AB - PSA screening is a tremendous burden for the pathologist, who has to see so many biopsies, but it is not only an intellectual burden to make a right diagnosis, it is also a real logistic burden. The TNM stage of the cancer detected has also changed. It's become more and more organ-confined cancer. Small volume of cancer in the biopsy is frequently consistent with an organ-confined cancer, but not necessarily with a small cancer. Another problem is the nonsense of the TNM (2002) staging of prostate cancer. You can have a voluminous cancer in one lobe with a bad prognosis which is classified as pT2b. Two or more small cancer foci in both lobes with a small tumor volume and good prognosis correspond to pT2c. Such a staging does not make any sense, and should be changed in the future. One of the most frequent (up to 90%) lesions encountered in prostate biopsies are the atrophic areas. Inexperienced pathologists can easily mistake this lesion for cancer. These nuclei are really ugly looking, and if you use proliferation markers, they proliferate like cancer, or even more. The chromosomal marker most frequently associated with prostate cancer genesis and progression is the long arm of 8q24. PMID- 17269618 TI - Merging digital rectal exam, family history, age and prostate-specific antigen to create a decision-making tool. AB - In this paper, we report on risk factors for prostate cancer detection on biopsy as found in the Prostate Cancer Prevention Trial (PCPT), with special emphasis on the independent contribution of prostate-specific antigen (PSA) velocity to prostate cancer risk over that provided by PSA. For this study, we used a subset of PCPT placebo arm participants who had had at least one prostate biopsy and a digital rectal examination (DRE) and PSA measured within 1 year prior to biopsy. In order to evaluate PSA velocity, we also required an additional PSA measurement within 3 years prior to biopsy, yielding 5,519 PCPT placebo arm participants for inclusion in the analysis. The risk of prostate cancer rose from 11.1% for PSA values less than 1 ng/mL to 43.3% for PSA values greater than 6 ng/mL and the risk of high-grade disease rose from 1.0% to 22.0% across these two PSA intervals. It was in fact no longer statistically significant as soon as the single predictor PSA was added to the risk equation, whereas PSA remained statistically significant even when velocity was in the risk equation. Furthermore, in a head-to-head comparison of predictive strength as a single predictor in a model, assessed by maximized log likelihood, PSA was more predictive than PSA velocity. These findings occurred for every definition of velocity that was considered and hence we concluded that velocity did not add independent prognostic information to prostate cancer risk over that provided by PSA. Similarly, age, which is also a predictor of prostate cancer in the absence of other factors, did not add independent prognostic information to PSA, DRE, family history, and prior biopsy. PMID- 17269619 TI - The role of PSA in secondary screening of the same population. AB - This presentation addresses the value of PSA in populations of men that have already been screened, using PSA with an arbitrary cut-off point as a biopsy indication (data from the European Randomised Study of Screening for Prostate Cancer ERSPC, section Rotterdam). The positive predictive value of PSA, i.e., the percentage of men who have a positive biopsy at various PSA cut-off values, has been shown to be different in initial screens and secondary screens 4 years later by Raaijmakers et al. in 2003, using a PSA cut-off of 3 as a biopsy indication in first-round screening, The data refer to 1,850 men biopsied initially and 1,040 biopsied at repeat screening. The possible predictors of a positive biopsy in second-round screening were analysed using multivariate regression analysis. The most important positive predictors were 2-Log PSA, a positive rectal examination or transrectal ultrasonography, age, and a positive family history. The predictive value of PSA changes in pre-screened populations. PSA progression to an arbitrary cut-off of 3 or 4 ng/mL remained important and indicated a positive biopsy rate between 20 and 25% in second-round screening. PSAV is not a diagnostic marker in a screening setting. It may be a marker of cancer aggressiveness. For the time being, the use of arbitrary PSA cut-off values remains an important option for daily clinical practice. Common sense has to prevail until more valid information has become available for proper indications of biopsies in pre-screened populations. PMID- 17269620 TI - Screening of prostate cancer. Is it needed? Russian experience. AB - INTRODUCTION: The incidence rate of prostate cancer (PC) in Russia has increased from 9.3 to 16.5 per 100000 person-years making it the 4th commonest form of cancer in men. In spite of lack of evidence to justify the wide spread incorporation of PSA screening it continues to gain popularity. We present the results of the screening study, which was initiated at Blokhin Cancer Center in 1996. MATERIALS AND METHODS: 1129 healthy volunteers, 40-80 years old were recruited into the screening arm. Participants underwent 3 screening tests including total PSA measurement, digital rectal examination (DRE) and transrectal ultrasound (TRUS). 6-10 core biopsies were performed in patients with suspicious findings on DRE or TRUS and patients with PSA greater than 4 ng/ml. The control arm included 943 patients who were referred to our center between 1996 and 2001. RESULTS: Five yearly rounds of screening were performed with an overall cancer detection rate of 5.7% (64). 54 cancers were detected in the first round, 6 in the second, 3 in the third, 1 in the fourth and none in the fifth round. In patients with PSA between 4 and 10 ng/ml the sensitivity of total PSA was 92% with specificity 63%. The majority of patients with high grade PC (21 of 22) had PSA above 4 ng/ml. The sensitivity of DRE reached 54%, with a specificity 94% and PPV 24.7%. The sensitivity of TRUS was 65% with a specificity 92%, and PPV 22.4%. In the control arm prostate cancer was diagnosed in 489 (52%) of 943 patients with 79% having either locally advanced or metastatic disease. On the contrary, 80% of men in screening arm had clinically localized disease. 41% (22) of screened patients had high grade disease compared to 57% (538) in the control arm. Over 50% of screen detected patients were treated with radical prostatectomy or radiotherapy compared to only 25% in clinically diagnosed group. The overall 8 year survival of patients in the screening arm treated with definite therapy (radiotherapy or radical prostatectomy) was better than in patients treated conservatively, 66% versus 43% (p = 0.047). However, when adjusted to the stage the difference in survival was lost, 74% versus 56% (p = 0.2). CONCLUSION: Screening of PC enables detection of the disease at an earlier, localized stage. The increased detection of cases with organ-confined PC is hoped to result in a decreased number of cancer-specific deaths. PMID- 17269621 TI - PSA and the conservative treatment of early prostate cancer. AB - The large difference between the incidence of prostate cancer and mortality from this disease suggests that a large number of men do not require treatment. As a result of the epidemiologic trends observed, a growing number of urologists recognize that many men with newly diagnosed localized disease can be treated conservatively for many years without adverse consequences. We recently published a twenty-year update of the large cohort of men diagnosed with clinically localized prostate cancer in Connecticut. From this study we have learned that men with high-grade disease, specifically Gleason score 7-10 prostate cancers, have a significant risk of dying from their disease if left untreated. Men with low-grade disease (Gleason score 2-6 tumors) have a remarkably indolent course over a period of twenty years. Fewer than 20% of these men died from clinically localized prostate cancer when managed conservatively. Based on our analysis of over 1,800 men diagnosed with localized prostate cancer in Connecticut between 1990 and 1992, we found that during the past two decades there has been a significant shift in the use of the Gleason scoring system. Gleason score 2-5 tumors ten years ago are much more likely to be scored as Gleason 6 tumors in contemporary practice. Men with high-grade prostate cancers (Gleason scores 7-10) face a significant risk of disease progression and death if managed expectantly. Men with low grade prostate cancers (Gleason scores 6 or less) face a much more ambiguous outcome. Some researchers suggest tracking PSA doubling times as a way of separating those patients with indolent disease from those who are likely to experience progression. PMID- 17269622 TI - New answers from the Prostate Cancer Prevention Trial on the chemoprevention of prostate cancer. AB - In this paper, we report ongoing investigations concerning the increased number of high-grade (Gleason grade > or = 7) prostate cancer, despite a reduction in all prostate cancer, found on the finasteride arm of the Prostate Cancer Prevention Trial (PCPT). There was a statistically significant 24.8% reduction in prostate cancer found on biopsy on the finasteride arm compared to placebo, and the reduction was also observed in both groups of end-of-study and for-cause biopsies. However, when the prostate cancers were examined by Gleason score, there was an increased number of high-grade prostate cancers found on the finasteride arm than on the placebo arm. This observation was emphasized in the editorial to the first publication of PCPT results and has dampened enthusiasm for recommendation of finasteride for chemoprevention. So, what are the potential reasons for increased grade on the finasteride arm? The number of high-grade cancers that are detected following a PSA prompt is directly proportional to the sensitivity of PSA for high-grade disease times the actual but unknown number of high-grade disease cases. So the higher the sensitivity the more likely one is to detect more of the existing high-grade cases irrespective of the true number of cases, i.e., there is an ascertainment bias. We are currently performing a quantitative investigation of whether or not this ascertainment bias could explain the higher number of high-grade disease cases observed on the finasteride arm. PMID- 17269623 TI - Europa Uomo: The European Prostate Cancer Coalition. AB - The European Prostate Cancer Coalition is an independent, international, non profit association of patient led prostate cancer support groups. The coalition was legally established in June 2004 in Milan with support of the European School of Oncology and the Oncologic Centre Antwerp. Its membership represents now 18 European countries and interest is growing. The European survivors of prostate cancer, now about one million strong, have taken up their responsibility to get involved in the support the control of the disease and focus on prevention, optimal treatment and quality of life. PMID- 17269624 TI - PSA: an update. AB - We know there is no cut-off of PSA that can rule out prostate cancer, a little more than zero and you may be at risk, the problem is to know if you are at risk of dying from of this disease or not. So PSA is not so specific, and we know also that between 2 and 8 ng/ml there is no big difference, and that PSA is partly related to the transition zone. PSA is related to age and to the size of the transition zone, which is BPH, so you have to exclude this, and keep in mind the reference data that Joe Oesterling published in the JAMA in 1996 which is that PSA is age dependeant. I would say that for patients who are at high risk of dying of the disease, those who have a life expectancy of 10 or 15 years, that are under 60 and have high Gleason, if you consider treatment, then you have to treat them early if you want to cure them. But let's not overtreat patients who have no risk or limited risk of dying from prostate cancer, let's be more conservative. The difficulty is to define criteria. Age, of course, is the major criteria. High Gleason, i.e., a Gleason with pattern 4 or 5, and PSA velocity is very important. PMID- 17269625 TI - The undecimated wavelet decomposition and its reconstruction. AB - This paper describes the undecimated wavelet transform and its reconstruction. In the first part, we show the relation between two well known undecimated wavelet transforms, the standard undecimated wavelet transform and the isotropic undecimated wavelet transform. Then we present new filter banks specially designed for undecimated wavelet decompositions which have some useful properties such as being robust to ringing artifacts which appear generally in wavelet-based denoising methods. A range of examples illustrates the results. PMID- 17269626 TI - Accurate centerline detection and line width estimation of thick lines using the radon transform. AB - Centerline detection and line width estimation are important for many computer vision applications, e.g., road network extraction from high resolution remotely sensed imagery. Radon transform-based linear feature detection has many advantages over other approaches: for example, its robustness in noisy images. However, it usually fails to detect the centerline of a thick line due to the peak selection problem. In this paper, several key issues that affect the centerline detection using the radon transform are investigated. A mean filter is proposed to locate the true peak in the radon image and a profile analysis technique is used to further refine the line parameters. The theta-boundary problem of the radon transform is also discussed and the erroneous line parameters are corrected. Intensive experiments have shown that the proposed methodology is effective in finding the centerline and estimating the line width of thick lines. PMID- 17269627 TI - Flexible skew-symmetric shape model for shape representation, classification, and sampling. AB - Skewness of shape data often arises in applications (e.g., medical image analysis) and is usually overlooked in statistical shape models. In such cases, a Gaussian assumption is unrealistic and a formulation of a general shape model which accounts for skewness is in order. In this paper, we present a novel statistical method for shape modeling, which we refer to as the flexible skew symmetric shape model (FSSM). The model is sufficiently flexible to accommodate a departure from Gaussianity of the data and is fairly general to learn a "mean shape" (template), with a potential for classification and random generation of new realizations of a given shape. Robustness to skewness results from deriving the FSSM from an extended class of flexible skew-symmetric distributions. In addition, we demonstrate that the model allows us to extract principal curves in a point cloud. The idea is to view a shape as a realization of a spatial random process and to subsequently learn a shape distribution which captures the inherent variability of realizations, provided they remain, with high probability, within a certain neighborhood range around a mean. Specifically, given shape realizations, FSSM is formulated as a joint bimodal distribution of angle and distance from the centroid of an aggregate of random points. Mean shape is recovered from the modes of the distribution, while the maximum likelihood criterion is employed for classification. PMID- 17269628 TI - Example-based color transformation of image and video using basic color categories. AB - Color transformation is the most effective method to improve the mood of an image, because color has a large influence in forming the mood. However, conventional color transformation tools have a tradeoff between the quality of the resultant image and the amount of manual operation. To achieve a more detailed and natural result with less labor, we previously suggested a method that performs an example-based color stylization of images using perceptual color categories. In this paper, we extend this method to make the algorithm more robust and to stylize the colors of video frame sequences. We present a variety of results, arguing that these images and videos convey a different, but coherent mood. PMID- 17269629 TI - Morphological decomposition of 2-d binary shapes into modestly overlapped octagonal and disk components. AB - One problem with several leading morphological shape representation algorithms is the heavy overlapping among the representative disks of the same size. A shape component formed by grouping connected disk centers may use many heavily overlapping disks to represent a simple shape part. Sometimes, these representative disks form complicated structures. A generalized skeleton transform was recently introduced which allows a shape to be represented as a collection of modestly overlapped octagonal shape parts. However, the generalized skeleton transform needs to be applied many times. Furthermore, an octagonal component is not easily matched up with another octagonal component. In this paper, we describe a octagon-fitting algorithm which identifies a special maximal octagon for each image point in a given shape. This transform leads to the development of two new shape decomposition algorithms. These algorithms are more efficient to implement; the octagon-fitting algorithm only needs to be applied once. The components generated are better characterized mathematically. The disk components used in the second decomposition algorithm are more primitive than octagons and easily matched up with other disk components from another shape. The experiments show that the new decomposition algorithms produce as efficient representations as the old algorithm for both exact and approximate cases. A simple shape-matching algorithm using disk components is also demonstrated. PMID- 17269630 TI - Kernel regression for image processing and reconstruction. AB - In this paper, we make contact with the field of nonparametric statistics and present a development and generalization of tools and results for use in image processing and reconstruction. In particular, we adapt and expand kernel regression ideas for use in image denoising, upscaling, interpolation, fusion, and more. Furthermore, we establish key relationships with some popular existing methods and show how several of these algorithms, including the recently popularized bilateral filter, are special cases of the proposed framework. The resulting algorithms and analyses are amply illustrated with practical examples. PMID- 17269631 TI - Novel cooperative neural fusion algorithms for image restoration and image fusion. AB - To deal with the problem of restoring degraded images with non-Gaussian noise, this paper proposes a novel cooperative neural fusion regularization (CNFR) algorithm for image restoration. Compared with conventional regularization algorithms for image restoration, the proposed CNFR algorithm can relax need of the optimal regularization parameter to be estimated. Furthermore, to enhance the quality of restored images, this paper presents a cooperative neural fusion (CNF) algorithm for image fusion. Compared with existing signal-level image fusion algorithms, the proposed CNF algorithm can greatly reduce the loss of contrast information under blind Gaussian noise environments. The performance analysis shows that the proposed two neural fusion algorithms can converge globally to the robust and optimal image estimate. Simulation results confirm that in different noise environments, the proposed two neural fusion algorithms can obtain a better image estimate than several well known image restoration and image fusion methods. PMID- 17269632 TI - Multiresolution 3-D reconstruction from side-scan sonar images. AB - In this paper, a new method for the estimation of seabed elevation maps from side scan sonar images is presented. The side-scan image formation process is represented by a Lambertian diffuse model, which is then inverted by a multiresolution optimization procedure inspired by expectation-maximization to account for the characteristics of the imaged seafloor region. On convergence of the model, approximations for seabed reflectivity, side-scan beam pattern, and seabed altitude are obtained. The performance of the system is evaluated against a real structure of known dimensions. Reconstruction results for images acquired by different sonar sensors are presented. Applications to augmented reality for the simulation of targets in sonar imagery are also discussed. PMID- 17269633 TI - Optimal signature design for spread-spectrum steganography. AB - For any given host image or group of host images and any (block) transform domain of interest, we find the signature vector that when used for spread-spectrum (SS) message embedding maximizes the signal-to-interference-plus-noise ratio (SINR) at the output of the corresponding maximum-SINR linear filter. We establish that, under a (colored) Gaussian assumption on the transform domain host data, the same derived signature minimizes host distortion for any target message recovery error rate and maximizes the Shannon capacity of the covert steganographic link. Then, we derive jointly optimal signature and linear processor designs for SS embedding in linearly modified transform domain host data and demonstrate orders of magnitude improvement over current SS steganographic practices. Optimized multisignature/multimessage embedding in the same host data is studied as well. PMID- 17269634 TI - Matching pursuit-based region-of-interest image coding. AB - Matching pursuit (MP) is a multiresolution signal analysis method and can be used to render a selected region of an image with a specific quality. A novel, scalable, and progressive MP-based region-of-interest image-coding scheme is presented. The method is capable of providing a trade off between rate, distortion, and complexity. The method also provides an interactive way of information refinement for regions of an image with higher receiver's priority. By selecting a proper subset of the huge initial MP dictionary, using the method described in this paper, the complexity burden of MP analysis can be adapted to the computational power of the image encoder. PMID- 17269635 TI - Adaptive directional lifting-based wavelet transform for image coding. AB - We present a novel 2-D wavelet transform scheme of adaptive directional lifting (ADL) in image coding. Instead of alternately applying horizontal and vertical lifting, as in present practice, ADL performs lifting-based prediction in local windows in the direction of high pixel correlation. Hence, it adapts far better to the image orientation features in local windows. The ADL transform is achieved by existing 1-D wavelets and is seamlessly integrated into the global wavelet transform. The predicting and updating signals of ADL can be derived even at the fractional pixel precision level to achieve high directional resolution, while still maintaining perfect reconstruction. To enhance the ADL performance, a rate distortion optimized directional segmentation scheme is also proposed to form and code a hierarchical image partition adapting to local features. Experimental results show that the proposed ADL-based image coding technique outperforms JPEG 2000 in both PSNR and visual quality, with the improvement up to 2.0 dB on images with rich orientation features. PMID- 17269636 TI - Undersampled boundary pre-/postfilters for low bit-rate DCT-based block coders. AB - It has been well established that critically sampled boundary pre-/postfiltering operators can improve the coding efficiency and mitigate blocking artifacts in traditional discrete cosine transform-based block coders at low bit rates. In these systems, both the prefilter and the postfilter are square matrices. This paper proposes to use undersampled boundary pre- and postfiltering modules, where the pre-/postfilters are rectangular matrices. Specifically, the prefilter is a "fat" matrix, while the postfilter is a "tall" one. In this way, the size of the prefiltered image is smaller than that of the original input image, which leads to improved compression performance and reduced computational complexities at low bit rates. The design and VLSI-friendly implementation of the undersampled pre /postfilters are derived. Their relations to lapped transforms and filter banks are also presented. Two design examples are also included to demonstrate the validity of the theory. Furthermore, image coding results indicate that the proposed undersampled pre-/postfiltering systems yield excellent and stable performance in low bit-rate image coding. PMID- 17269637 TI - Robust coding over noisy overcomplete channels. AB - We address the problem of robust coding in which the signal information should be preserved in spite of intrinsic noise in the representation. We present a theoretical analysis for 1- and 2-D cases and characterize the optimal linear encoder and decoder in the mean-squared error sense. Our analysis allows for an arbitrary number of coding units, thus including both under- and over-complete representations, and provides insights into optimal coding strategies. In particular, we show how the form of the code adapts to the number of coding units and to different data and noise conditions in order to achieve robustness. We also present numerical solutions of robust coding for high-dimensional image data, demonstrating that these codes are substantially more robust than other linear image coding methods such as PCA, ICA, and wavelets. PMID- 17269638 TI - An exact algorithm for optimal MAE stack filter design. AB - We propose a new algorithm for optimal MAE stack filter design. It is based on three main ingredients. First, we show that the dual of the integer programming formulation of the filter design problem is a minimum cost network flow problem. Next, we present a decomposition principle that can be used to break this dual problem into smaller subproblems. Finally, we propose a specialization of the network Simplex algorithm based on column generation to solve these smaller subproblems. Using our method, we were able to efficiently solve instances of the filter problem with window size up to 25 pixels. To the best of our knowledge, this is the largest dimension for which this problem was ever solved exactly. PMID- 17269639 TI - The regularized iteratively reweighted MAD method for change detection in multi- and hyperspectral data. AB - This paper describes new extensions to the previously published multivariate alteration detection (MAD) method for change detection in bi-temporal, multi- and hypervariate data such as remote sensing imagery. Much like boosting methods often applied in data mining work, the iteratively reweighted (IR) MAD method in a series of iterations places increasing focus on "difficult" observations, here observations whose change status over time is uncertain. The MAD method is based on the established technique of canonical correlation analysis: for the multivariate data acquired at two points in time and covering the same geographical region, we calculate the canonical variates and subtract them from each other. These orthogonal differences contain maximum information on joint change in all variables (spectral bands). The change detected in this fashion is invariant to separate linear (affine) transformations in the originally measured variables at the two points in time, such as 1) changes in gain and offset in the measuring device used to acquire the data, 2) data normalization or calibration schemes that are linear (affine) in the gray values of the original variables, or 3) orthogonal or other affine transformations, such as principal component (PC) or maximum autocorrelation factor (MAF) transformations. The IR-MAD method first calculates ordinary canonical and original MAD variates. In the following iterations we apply different weights to the observations, large weights being assigned to observations that show little change, i.e., for which the sum of squared, standardized MAD variates is small, and small weights being assigned to observations for which the sum is large. Like the original MAD method, the iterative extension is invariant to linear (affine) transformations of the original variables. To stabilize solutions to the (IR-)MAD problem, some form of regularization may be needed. This is especially useful for work on hyperspectral data. This paper describes ordinary two-set canonical correlation analysis, the MAD transformation, the iterative extension, and three regularization schemes. A simple case with real Landsat Thematic Mapper (TM) data at one point in time and (partly) constructed data at the other point in time that demonstrates the superiority of the iterative scheme over the original MAD method is shown. Also, examples with SPOT High Resolution Visible data from an agricultural region in Kenya, and hyperspectral airborne HyMap data from a small rural area in southeastern Germany are given. The latter case demonstrates the need for regularization. PMID- 17269640 TI - A MAP approach for joint motion estimation, segmentation, and super resolution. AB - Super resolution image reconstruction allows the recovery of a high-resolution (HR) image from several low-resolution images that are noisy, blurred, and down sampled. In this paper, we present a joint formulation for a complex super resolution problem in which the scenes contain multiple independently moving objects. This formulation is built upon the maximum a posteriori (MAP) framework, which judiciously combines motion estimation, segmentation, and super resolution together. A cyclic coordinate descent optimization procedure is used to solve the MAP formulation, in which the motion fields, segmentation fields, and HR images are found in an alternate manner given the two others, respectively. Specifically, the gradient-based methods are employed to solve the HR image and motion fields, and an iterated conditional mode optimization method to obtain the segmentation fields. The proposed algorithm has been tested using a synthetic image sequence, the "Mobile and Calendar" sequence, and the original "Motorcycle and Car" sequence. The experiment results and error analyses verify the efficacy of this algorithm. PMID- 17269641 TI - Wiener filter-based error resilient time-domain lapped transform. AB - In this paper, the design of the error resilient time-domain lapped transform is formulated as a linear minimal mean-squared error problem. The optimal Wiener solution and several simplifications with different tradeoffs between complexity and performance are developed. We also prove the persymmetric structure of these Wiener filters. The existing mean reconstruction method is proven to be a special case of the proposed framework. Our method also includes as a special case the linear interpolation method used in DCT-based systems when there is no pre/postfiltering and when the quantization noise is ignored. The design criteria in our previous results are scrutinized and improved solutions are obtained. Various design examples and multiple description image coding experiments are reported to demonstrate the performance of the proposed method. PMID- 17269642 TI - Detection of gait characteristics for scene registration in video surveillance system. AB - This paper presents a robust walk-detection algorithm, based on our symmetry approach which can be used to extract gait characteristics from video-image sequences. To obtain a useful descriptor of a walking person, we temporally track the symmetries of a person's legs. Our method is suitable for use in indoor or outdoor surveillance scenes. Determining the leading leg of the walking subject is important, and the presented method can identify this from two successive walk steps (one walk cycle). We tested the accuracy of the presented walk-detection method in a possible application: Image registration methods are presented which are applicable to multicamera systems viewing human subjects in motion. PMID- 17269643 TI - Correction of simple contrast loss in color images. AB - This paper is concerned with the mitigation of simple contrast loss due to added lightness in an image. This added lightness has been referred to as "airlight" in the literature since it is often caused by optical scattering due to fog or mist. A statistical model for scene content is formulated that gives a way of detecting the presence of airlight in an arbitrary image. An algorithm is described for estimating the level of this airlight given the assumption that it is constant throughout the image. This algorithm is based on finding the minimum of a global cost function and is applicable to both monochrome and color images. The method is robust and insensitive to scaling. Once an estimate of airlight is achieved, then image correction is straightforward. The performance of the algorithm is explored using the Monte Carlo simulation with synthetic images under different statistical assumptions. Several examples of before and after color images are given. Results with real video data obtained in poor visibility conditions indicate frame-to-frame consistency of better than 1% of maximum level. PMID- 17269644 TI - Image denoising by averaging of piecewise constant simulations of image partitions. AB - This paper investigates the problem of image denoising when the image is corrupted by additive white Gaussian noise. We herein propose a spatial adaptive denoising method which is based on an averaging process performed on a set of Markov Chain Monte-Carlo simulations of region partition maps constrained to be spatially piecewise uniform (i.e., constant in grey level value sense) for each estimated constant-value regions. For the estimation of these region partition maps, we have adopted the unsupervised Markovian framework in which parameters are automatically estimated in the least square sense. This sequential averaging allows to obtain, under our image model, an approximation of the image to be recovered in the minimal mean square sense error. The experiments reported in this paper demonstrate that the discussed method performs competitively and sometimes better than the best existing state-of-the-art wavelet-based denoising methods in benchmark tests. PMID- 17269645 TI - Iterative regularization and nonlinear inverse scale space applied to wavelet based denoising. AB - In this paper, we generalize the iterative regularization method and the inverse scale space method, recently developed for total-variation (TV) based image restoration, to wavelet-based image restoration. This continues our earlier joint work with others where we applied these techniques to variational-based image restoration, obtaining significant improvement over the Rudin-Osher-Fatemi TV based restoration. Here, we apply these techniques to soft shrinkage and obtain the somewhat surprising result that a) the iterative procedure applied to soft shrinkage gives firm shrinkage and converges to hard shrinkage and b) that these procedures enhance the noise-removal capability both theoretically, in the sense of generalized Bregman distance, and for some examples, experimentally, in terms of the signal-to-noise ratio, leaving less signal in the residual. PMID- 17269646 TI - Video inpainting under constrained camera motion. AB - A framework for inpainting missing parts of a video sequence recorded with a moving or stationary camera is presented in this work. The region to be inpainted is general: it may be still or moving, in the background or in the foreground, it may occlude one object and be occluded by some other object. The algorithm consists of a simple preprocessing stage and two steps of video inpainting. In the preprocessing stage, we roughly segment each frame into foreground and background. We use this segmentation to build three image mosaics that help to produce time consistent results and also improve the performance of the algorithm by reducing the search space. In the first video inpainting step, we reconstruct moving objects in the foreground that are "occluded" by the region to be inpainted. To this end, we fill the gap as much as possible by copying information from the moving foreground in other frames, using a priority-based scheme. In the second step, we inpaint the remaining hole with the background. To accomplish this, we first align the frames and directly copy when possible. The remaining pixels are filled in by extending spatial texture synthesis techniques to the spatiotemporal domain. The proposed framework has several advantages over state-of-the-art algorithms that deal with similar types of data and constraints. It permits some camera motion, is simple to implement, fast, does not require statistical models of background nor foreground, works well in the presence of rich and cluttered backgrounds, and the results show that there is no visible blurring or motion artifacts. A number of real examples taken with a consumer hand-held camera are shown supporting these findings. PMID- 17269647 TI - A successive approximation technique for displaying gray shades in liquid crystal displays (LCDs). AB - A successive approximation technique that is based on the conventional line-by line-addressing is proposed. A large number of gray shades can be displayed without flicker by using low-cost liquid crystal display drivers that are designed to drive the pixels to either ON or OFF states in bilevel displays. PMID- 17269648 TI - Effective image retrieval based on hidden concept discovery in image database. AB - This paper addresses content-based image retrieval in general, and in particular, focuses on developing a hidden semantic concept discovery methodology to address effective semantics-intensive image retrieval. In our approach, each image in the database is segmented into regions associated with homogenous color, texture, and shape features. By exploiting regional statistical information in each image and employing a vector quantization method, a uniform and sparse region-based representation is achieved. With this representation, a probabilistic model based on statistical-hidden-class assumptions of the image database is obtained, to which the expectation-maximization technique is applied to analyze semantic concepts hidden in the database. An elaborated retrieval algorithm is designed to support the probabilistic model. The semantic similarity is measured through integrating the posterior probabilities of the transformed query image, as well as a constructed negative example, to the discovered semantic concepts. The proposed approach has a solid statistical foundation; the experimental evaluations on a database of 10000 general-purposed images demonstrate its promise and effectiveness. PMID- 17269649 TI - Three-dimensional volume and position recovering using a virtual reference box. AB - This paper proposes a procedure to determine the position and volumetric information of a 3-D object, based on two previously calibrated camera images. The positioning and volumetric information is achieved by inscribing the object in a virtual bounding box, created from known vertices and vanishing points. The images of a starting virtual box are adjusted to fit a region of interest around each projection of the solid object. The volumes and positions defined by the adjusted boxes are approximations for the dimensions and location of the solid. The work displays the application of such a technique in an automated manufacturing process. PMID- 17269650 TI - LDPC-based iterative joint source-channel decoding for JPEG2000. AB - A framework is proposed for iterative joint source-channel decoding of JPEG2000 codestreams. At the encoder, JPEG2000 is used to perform source coding with certain error-resilience (ER) modes, and LDPC codes are used to perform channel coding. During decoding, the source decoder uses the ER modes to identify corrupt sections of the codestream and provides this information to the channel decoder. Decoding is carried out jointly in an iterative fashion. Experimental results indicate that the proposed method requires fewer iterations and improves overall system performance. PMID- 17269651 TI - Accurate computation of Zernike moments in polar coordinates. AB - An algorithm for high-precision numerical computation of Zernike moments is presented. The algorithm, based on the introduced polar pixel tiling scheme, does not exhibit the geometric error and numerical integration error which are inherent in conventional methods based on Cartesian coordinates. This yields a dramatic improvement of the Zernike moments accuracy in terms of their reconstruction and invariance properties. The introduced image tiling requires an interpolation algorithm which turns out to be of the second order importance compared to the discretization error. Various comparisons are made between the accuracy of the proposed method and that of commonly used techniques. The results reveal the great advantage of our approach. PMID- 17269652 TI - Effect of polycyclic aromatic hydrocarbons on detection sensitivity of ultratrace nitroaromatic compounds. AB - Polycyclic aromatic hydrocarbons (PAHs) with different numbers of pi-electrons and geometric symmetry of pi-systems, including anthracene, phenanthrene, pyrene, triphenylene, perylene, benzo[ghi]perylene, and coronene, were chosen to modify glassy carbon electrodes (GCEs) by self-assembling. The self-assembled monolayer of PAHs was investigated by STM and was used in the electrochemical detection of nitroaromatic compounds (NACs). The results indicate that PAH-modified GCE shows higher sensitivity to NACs than an unmodified one. Among the seven different PAHs, coronene-modified GCE exhibits the highest sensitivity to 2,4,6 trinitrotoluene and 1,3,5-trinitrobenzene. PMID- 17269653 TI - Detection of chemical warfare-related species on complex aerosol particles deposited on surfaces using an ion trap-based aerosol mass spectrometer. AB - A new type of aerosol mass spectrometer was developed by minimal modification of an existing commercial ion trap to analyze the semivolatile components of aerosols in real time. An aerodynamic lens-based inlet system created a well collimated particle beam that impacted into the heated ionization volume of the commercial ion trap mass spectrometer. The semivolatile components of the aerosols were thermally vaporized and ionized by electron impact or chemical ionization in the source. The nascent ions were extracted and injected into the ion trap for mass analysis. The utility of this instrument was demonstrated by identifying semivolatile analytes in complex aerosols. This study is part of an ongoing effort to develop methods for identifying chemical species related to CW agent exposure. Our efforts focused on detection of CW-related species doped on omnipresent aerosols such as house dust particles vacuumed from various surfaces found in any office building. The doped aerosols were sampled directly into the inlet of our mass spectrometer from the vacuumed particle stream. The semivolatile analytes were deposited on house dust and identified by positive ion chemical ionization mass spectrometry up to 2.5 h after deposition. Our results suggest that the observed semivolatile species may have been chemisorbed on some of the particle surfaces in submonolayer concentrations and may remain hours after deposition. This research suggests that identification of trace CW agent related species should be feasible by this technique. PMID- 17269654 TI - Fluorescence lifetime standards for time and frequency domain fluorescence spectroscopy. AB - A series of fluorophores with single-exponential fluorescence decays in liquid solution at 20 degrees C were measured independently by nine laboratories using single-photon timing and multifrequency phase and modulation fluorometry instruments with lasers as excitation source. The dyes that can serve as fluorescence lifetime standards for time-domain and frequency-domain measurements are all commercially available, are photostable under the conditions of the measurements, and are soluble in solvents of spectroscopic quality (methanol, cyclohexane, water). These lifetime standards are anthracene, 9-cyanoanthracene, 9,10-diphenylanthracene, N-methylcarbazole, coumarin 153, erythrosin B, N-acetyl l-tryptophanamide, 1,4-bis(5-phenyloxazol-2-yl)benzene, 2,5-diphenyloxazole, rhodamine B, rubrene, N-(3-sulfopropyl)acridinium, and 1,4-diphenylbenzene. At 20 degrees C, the fluorescence lifetimes vary from 89 ps to 31.2 ns, depending on fluorescent dye and solvent, which is a useful range for modern pico- and nanosecond time-domain or mega- to gigahertz frequency-domain instrumentation. The decay times are independent of the excitation and emission wavelengths. Dependent on the structure of the dye and the solvent, the excitation wavelengths used range from 284 to 575 nm, the emission from 330 to 630 nm. These lifetime standards may be used to either calibrate or test the resolution of time- and frequency-domain instrumentation or as reference compounds to eliminate the color effect in photomultiplier tubes. Statistical analyses by means of two-sample charts indicate that there is no laboratory bias in the lifetime determinations. Moreover, statistical tests show that there is an excellent correlation between the lifetimes estimated by the time-domain and frequency-domain fluorometries. Comprehensive tables compiling the results for 20 (fluorescence lifetime standard/solvent) combinations are given. PMID- 17269655 TI - Reactive desorption electrospray ionization linear ion trap mass spectrometry of latest-generation counterfeit antimalarials via noncovalent complex formation. AB - Desorption electrospray ionization mass spectrometry (DESI MS) is rapidly becoming accepted as a powerful surface characterization tool for a wide variety of samples in the open air. Besides its well-established high-throughput capabilities, a unique feature of DESI is that chemical reactions between the charged spray microdroplets and surface molecules can be exploited to enhance ionization. Here, we present a rapid screening assay for artesunate antimalarials based on reactive DESI. Artesunate is a vital therapy for Plasmodium falciparum malaria, but artesunate tablets have been counterfeited on a very large scale in SE Asia, and more recently in Africa. For this reason, faster and more sensitive screening tests are urgently needed. The proposed DESI assay is based on the formation of stable noncovalent complexes between linear alkylamines dissolved in the DESI spray solution and artesunate molecules exposed on the tablet surface. We found that, depending on amine type and concentration, a sensitivity gain of up to 170x can be obtained, in comparison to reagent-less DESI. Hexylamine (Hex), dodecylamine (DDA), and octadecylamine (ODA) produced proton-bound noncovalent complexes with gas-phase stabilities, increasing in the order [M + Hex + H]+ < [M + DDA + H]+ < [M + ODA + H]+. Tandem MS experiments revealed that complex formation occurred by hydrogen bonding between the amine nitrogen and the ether like moieties within the artesunate lactone ring. After the reactive DESI assay was fully characterized, it was applied to a set of recently collected suspicious artesunate tablets purchased in shops and pharmacies in SE Asia. Not only did we find that these samples were counterfeits, but we also detected the presence of several wrong active ingredients. Of particular concern was the positive detection of artesunate traces in the surface of one of the samples, which we quantified with standard chromatographic techniques. PMID- 17269656 TI - Sequence-dependent nucleosome structure and stability variations detected by Forster resonance energy transfer. AB - Nucleosomes, the basic unit of eukaryotic chromosome structure, cover most of the DNA in eukaryotes, including regulatory sequences. Here, a recently developed Forster resonance energy transfer approach is used to compare structure and stability features of sea urchin 5S nucleosomes and nucleosomes reconstituted on two promoter sequences that are nucleosomal in vivo, containing the yeast GAL10 TATA or the major transcription response elements from the mouse mammary tumor virus promoter. All three sequences form mononucleosomes with similar gel mobilities and similar stabilities at moderate salt concentrations. However, the two promoter nucleosomes differ from 5S nucleosomes in (1) diffusion coefficient values, which suggest differences in nucleosome compaction, (2) intrinsic FRET efficiencies (in solution or in gels), and (3) the response of FRET efficiency to high (>or=600 mM) NaCl concentrations, subnanomolar nucleosome concentrations, and elevated temperatures (to 42 degrees C). These results indicate that nucleosome features can vary depending on the DNA sequence they contain and show that this fluorescence approach is sufficiently sensitive to detect such differences. Sequence-dependent variations in nucleosome structure or stability could facilitate specific nucleosome recognition, working together with other known genomic regulatory mechanisms. The variations in salt-, concentration-, and temperature-dependent responses all occur under conditions that have been shown previously to produce release of H2A-H2B dimers or terminal DNA from nucleosomes and could thus involve differences in those processes, as well as in other features. PMID- 17269657 TI - ATP-dependent transport of phosphatidylserine analogues in human erythrocytes. AB - The plasma membrane of most cells contains a number of lipid transporters that catalyze the ATP-dependent movement of phospholipids across the membrane and assist in the maintenance of lipid asymmetry. The most well-characterized of these transporters is the erythrocyte aminophospholipid flippase, which selectively transports phosphatidylserine (PS) from the outer to the inner monolayer. Previous work has demonstrated that PS and to a lesser extent phosphatidylethanolamine (PE) are substrates for the flippase and that other phospholipids move across the membrane only by passive flip-flop. The present study re-evaluates these results. The incorporation and transbilayer movement of a number of short-chain (dilauroyl) phospholipid analogues in human erythrocytes was measured by observing lipid-induced changes in cell morphology, and the effect of an ATPase inhibitor (vanadate) and a sulfyhdryl reagent (N ethylmaleimide) was determined. Incubation of cells with these lipids causes the rapid formation of echinocytes, because of the accumulation of the lipid in the outer monolayer. While dilauroylphosphatidylcholine-treated cells retained this shape, cells treated with sn-1,2-DLP-l-S, sn-1,2-DLP-d-S, or N-methyl-DLPS rapidly changed morphology to stomatocytes, which is consistent with the transport and accumulation of the lipid in the inner monolayer. A similar, although slower, stomatocytic shape change was induced by sn-2,3-DLP-l-S. Other lipids that were tested (dilauroylphosphatidylhydroxypropionate, dilauroylphosphatidylhomoserine, DLPS-methyl ester, or sn-2,3-DLP-d-S) reverted to discocytes only. In all cases, pretreatment with vanadate or N-ethylmaleimide inhibited the conversion of echinocytes to discocytes or stomatocytes. This is the first report of a protein- and energy-dependent pathway for the inwardly directed transbilayer movement of lipids other than PS and PE in the erythrocyte membrane and suggests that the flippase has broader specificity for substrates or that other lipid transporters are present. PMID- 17269658 TI - A new mutant of bovine seminal ribonuclease with a reversed swapping propensity. AB - Bovine seminal ribonuclease (BS-RNase) is made up of two identical subunits bridged through two disulfide bonds. In solution, it exists as a 2:1 equilibrium mixture between two forms, with (MxM) and without swapping (M=M) of the N terminal arms. The swapping endows BS-RNase with some special biological functions, including antitumor activity, since MxM retains a dimeric structure even under reducing conditions, thus evading the cytosolic ribonuclease inhibitor. To investigate the structural basis of domain swapping in BS-RNase, we have obtained several mutants by replacing selected residues with the corresponding ones of its monomeric counterpart, bovine pancreatic ribonuclease (RNase A). We have already shown that, in contrast with all other cases of swapped proteins, the swapping propensity of BS-RNase does not depend on the specific sequence of the 16-22 hinge loop, which connects the main body to the dislocating arm. In this paper we report the design, the expression, and the structural characterization of two mutants obtained by replacing Arg80 with Ser either in BS-RNase or in the mutant already containing the 16-22 hinge sequence of RNase A. NMR and circular dichroism data indicate that, in the monomeric form of the latter mutant, Ser80 acts as a switch for the conformation of the hinge region. Accordingly, in the dimeric form of the same mutant the MxM:M=M equilibrium ratio is inverted to 1:2. Overall, these data suggest that the presence of Arg80 triggers the swapping of N-terminal ends and plays a relevant role in the stability of the swapped form of BS-RNase. PMID- 17269659 TI - DNA bending versus DNA end joining activity of HMGB1 protein is modulated in vitro by acetylation. AB - The ability of HMGB1 protein to recognize bent DNA and to induce bending in linear duplex DNA defines HMGB1 as an architectural factor. It has already been demonstrated that the binding affinity of the protein for various bent DNA structures is enhanced upon in vivo acetylation at Lys2. Here we investigate how this modification of HMGB1 affects its ability to bend DNA. We report that the modified protein cannot bend short DNA fragments but, instead, stimulates joining of the same fragments via their ends. The same properties are exhibited in vivo by acetylated HMGB1 lacking its acidic tail. Further, in vitro acetylation of the truncated protein at Lys81 (possible upon tail removal only) restores the protein's bending ability, while the level of stimulation of DNA end joining is strongly reduced. We conclude, therefore, that the ability of HMGB1 to bend DNA or to stimulate end joining is modulated in vitro by acetylation. In an attempt to explain the properties of in vivo-acetylated HMGB1, its complexes with DNA have been analyzed by both protein-DNA cross-linking and atomic force microscopy. Unlike the parental protein, bound mainly within the internal sequences, acetylated HMGB1 binds preferentially to DNA ends. We propose that the loading of acetylated protein on DNA ends accounts for both the failure to bend DNA and the stimulation of DNA end joining. PMID- 17269660 TI - In silico mutation of cysteine residues in the ligand-binding domain of an N methyl-D-aspartate receptor. AB - The precise nature of redox modulation of N-methyl-d-aspartate (NMDA) receptors is still unclear, although it is thought to be related to the formation and breaking of disulfide bonds. Recent structural data demonstrated the way in which disulfide bonds in the ligand-binding core of the NR1 subunit are arranged. However, the structures were not able to reconcile existing experimental data that examined the effects of mutating these cysteine residues. We have used molecular dynamics (MD) simulations of a series of in silico mutations to try and address this in terms of the current structure of the NR1 ligand-binding domain. A double mutation that removes the disulfide bridge between C744 and C798 gives rise to greater interlobe mobility which was predicted from the crystal structure information but, unexpectedly, also appears to predispose the receptor toward greater flexibility in the hinge region. Removal of the disulfide bond between C454 and C420 did not show any appreciable difference from the "wild-type" simulation, suggesting that removal of this would not change receptor properties, which is in agreement with experimental findings. Furthermore, the position of the C454 side chain could be characterized into discrete rotamers, which may reflect the observation of alternative density in the crystal structure for this residue. Simulations in which two of the disulfide bonds are removed via mutations to alanine (C420A and C436A) resulted in a tendency of the protein to adopt a partially closed conformation. PMID- 17269661 TI - Probing the opening of the pancreatic lipase lid using site-directed spin labeling and EPR spectroscopy. AB - Access to the active site of human pancreatic lipase (HPL) is controlled by a surface loop (the lid) that undergoes a conformational change in the presence of amphiphiles and lipid substrate. The question of how and when the lid opens still remains to be elucidated, however. A paramagnetic probe was covalently bound to the lid via the D249C mutation, and electron paramagnetic resonance (EPR) spectroscopy was used to monitor the conformational change in solution. Two EPR spectral components, corresponding to distinct mobilities of the probe, were attributed to the closed and open conformations of the HPL lid, based on experiments performed with the E600 inhibitor. The open conformation of the lid was observed in solution at supramicellar bile salt concentrations. Colipase alone did not induce lid opening but increased the relative proportions of the open conformation in the presence of bile salts. The opening of the lid was found to be a reversible process. Using various colipase to lipase molar ratios, a correlation between the proportion of the open conformation and the catalytic activity of HPL was observed. PMID- 17269663 TI - Painting and printing living bacteria: engineering nanoporous biocatalytic coatings to preserve microbial viability and intensify reactivity. AB - Latex biocatalytic coatings containing approximately 50% by volume of microorganisms stabilize, concentrate and preserve cell viability on surfaces at ambient temperature. Coatings can be formed on a variety of surfaces, delaminated to generate stand-alone membranes or formulated as reactive inks for piezoelectric deposition of viable microbes. As the latex emulsion dries, cell preservation by partial desiccation occurs simultaneously with the formation of pores and adhesion to the substrate. The result is living cells permanently entrapped, surrounded by nanopores generated by partially coalesced polymer particles. Nanoporosity is essential for preserving microbial viability and coating reactivity. Cryo-SEM methods have been developed to visualize hydrated coating microstructure, confocal microscopy and dispersible coating methods have been developed to quantify the activity of the entrapped cells, and FTIR methods are being developed to determine the structure of vitrified biomolecules within and surrounding the cells in dry coatings. Coating microstructure, stability and reactivity are investigated using small patch or strip coatings where bacteria are concentrated 102- to 103-fold in 5-75 microm thick layers with pores formed by carbohydrate porogens. The carbohydrate porogens also function as osmoprotectants and are postulated to preserve microbial viability by formation of glasses inside the microbes during coat drying; however, the molecular mechanism of cell preservation by latex coatings is not known. Emerging applications include coatings for multistep oxidations, photoreactive coatings, stabilization of hyperthermophiles, environmental biosensors, microbial fuel cells, as reaction zones in microfluidic devices, or as very high intensity (>100 g.L-1 coating volume.h-1) industrial or environmental biocatalysts. We anticipate expanded use of nanoporous adhesive coatings for prokaryotic and eukaryotic cell preservation at ambient temperature and the design of highly reactive "living" paints and inks. PMID- 17269664 TI - Engineering the stem cell microenvironment. AB - Multipotent stem cells in the body facilitate tissue regeneration, growth, and wound healing throughout life. The microenvironment in which they reside provides signals that direct these progenitors to proliferate, differentiate, or remain dormant; these factors include soluble molecules, the extracellular matrix, neighboring cells, and physical stimuli. Recent advances in the culture of embryonic stem cells and adult progenitors necessitate an increased understanding of these phenomena. Here, we summarize the interactions between stem cells and their local environment, drawing on in vivo observations and tissue culture studies. In addition, we describe novel methods of characterizing the effects of various environmental factors and review new techniques that enable scientists and engineers to more effectively direct stem cell fate. PMID- 17269665 TI - Emerging technologies: systems biology. AB - The field of systems biology is based on the paradigm that the whole is greater than the sum of the parts. Through a combination of high-throughput experiments analyzing "-omic" scale phenomenon and the development of new computational techniques and algorithms, it is now feasible to study biological systems in a way that was previously not possible. During the 232nd National Meeting of the American Chemical Society, a session devoted to the emerging technology of Systems Biology was held. A number of talks on a wide variety of subjects covering cell signaling, network regulation and analysis, novel experimental procedures, synthetic biology, and metabolic flux analysis were presented. All of these approaches shared the common theme of using a systems biology approach to aid in the understanding of fundamental biology, with an eye toward applications for the benefit of society. PMID- 17269666 TI - Protein and cellular engineering with unnatural amino acids. AB - Proteins are the central functional constituents in all living organisms ranging from viruses, bacteria, yeast, and plants to mammals. All of these biopolymers that are formed by natural biosynthetic pathways are composed of a genetically determined sequence of the 20 so-called natural amino acids. The physical and chemical properties of proteins are a reflection of the side chains of each of the component amino acids. However, for some purposes it would be very desireable to have amino acids with side chains of various selected physical chemical properties, such as a keto group, a crosslinker, or a NMR probe group, incorporated into the protein. Although chemical and biochemical methods for modifying amino acid moieties in proteins have been achieved, recent successes in incorporating unnatural amino acids in vivo open entirely new avenues for determining protein functions in vivo and for the creation of unnatural proteins with novel functionalities. Several examples by employing the novel activity of unnatural amino acids have shown significant roles in both basic research and biotechnology. PMID- 17269667 TI - Nanoparticle-mediated drug delivery and gene therapy. AB - Biomedical application of nanotechnology is a rapidly developing area that raises new prospect in the improvement of diagnosis and treatment of human diseases. The ability to incorporate drugs or genes into a functionalized nanoparticle demonstrates a new era in pharmacotherapy for delivering drugs or genes selectively to tissues or cells. It is envisioned that the transfer of nanoengineering capability into disease therapy will provide constant and concentrated drug delivery to targeted tissues, minimizing systemic side effects and toxicity. We have in this article highlighted the recent state of the art in nanomedicine, focusing particularly on the achievement of nanotechnology in nanoscale drug and gene delivery in vitro and in vivo. In addition, a specific emphasis has been placed on the use of nanotechnology to improve controlled drug release and sustainable drug delivery in solid tumors and on new drug therapies for age-related neurodegenerative disorders. PMID- 17269668 TI - Alternatives to chromatographic separations. AB - Up to now, the productivity of mammalian cell culture has been perceived as limiting the productivity of the industrial manufacture of therapeutic monoclonal antibodies. Dramatic improvements in cell culture performance have changed this picture, and the throughput of antibody purification processes is gaining increasing attention. Although chromatographic separations currently are the centerpiece of antibody purification, mostly due to their high resolving power, it becomes more and more apparent that there may be limitations at the very large scale. This review will discuss a number of alternatives to chromatographic antibody purification, with a particular emphasis on the ability to increase throughput and overcome traditional drawbacks of column chromatography. Specifically, precipitation, membrane chromatography, high-resolution ultrafiltration, crystallization, and high-pressure refolding will be evaluated as potential large scale unit operations for industrial antibody production. PMID- 17269669 TI - Cell culture process development: advances in process engineering. AB - Representatives from the cell culture process development community met on September 11 and 12, 2006 at the ACS National Meeting in San Francisco to discuss "Cell Culture Process Development: Advances in Process Engineering". This oral session was held as part of the Division of Biochemical Technology (BIOT) program. The presentations addressed the very small scale (less than 1 mL) to the very large scale (20,000 L). The topics covered included development of high throughput cell culture screening systems, modeling and characterization of bioreactor environments from mixing and shear perspectives at both small and large scales, systematic approaches for improving scale-up and scale-down activities, development of disposable bioreactor technologies, and novel perfusion culture approaches. All told, this well-attended session resulted in a valuable exchange of technical information and demonstrated a high level of interest within the process development community. PMID- 17269670 TI - A window into biocatalysis and biotransformations. AB - Eight papers were presented in this year's symposium "Advances in Biocatalysis" at the 232nd ACS National Meeting, accentuating the most recent development in biocatalysis. Researchers from both industry and academia are addressing several fundamental problems in biocatalysis, including the limited number of commercially available enzymes that can be provided in bulk quantities, the limited enzyme stability and activity in nonaqueous environments, and the permeability issue and cell localization problems in whole-cell systems. A trend that can be discerned from these eight talks is the infusion of new tools and technologies in addressing various challenges facing biocatalysis. Nanotechnology, bioinformatics, cellular membrane engineering and metabolic engineering (for engineering whole-cell catalysts), and protein engineering (to improve enzymes and create novel enzymes) are becoming more routinely used in research laboratories and are providing satisfactory solutions to the problems in biocatalysis. Significant progress in various aspects of biocatalysis from discovery to industrial applications was highlighted in this symposium. PMID- 17269671 TI - Using statistical analysis for setting process validation acceptance criteria for biotech products. AB - This paper discusses the challenges of setting process validation acceptance criteria for biotech products for cases where using statistical tools is appropriate. Data are analyzed under three different scenarios that are frequently encountered in biotech applications. Scenario A represents the case when a small data set around center point conditions is available for setting acceptance criteria. Scenario B represents the case when a larger data set within normal operation conditions is available for setting acceptance criteria. Scenario C represents the case when a large characterization data set is available for setting acceptance criteria and it is possible to accurately model the impact of operation conditions on performance of the step. Statistical approaches including mean +/- 3SD, tolerance interval analysis, prediction profiler, and Monte Carlo simulation are applied to the different scenarios. Strengths and shortcomings of the different statistical tools are discussed, and the best approach for each scenario is recommended. It is shown that selection of the right statistical approach is a critical first step toward setting appropriate acceptance criteria. PMID- 17269672 TI - Application of multivariate analysis toward biotech processes: case study of a cell-culture unit operation. AB - This paper examines the feasibility of using multivariate data analysis (MVDA) for supporting some of the key activities that are required for successful manufacturing of biopharmaceutical products. These activities include scale-up, process comparability, process characterization, and fault diagnosis. Multivariate data analysis and modeling were performed using representative data from small-scale (2 L) and large-scale (2000 L) batches of a cell-culture process. Several input parameters (pCO2, pO2, glucose, pH, lactate, ammonium ions) and output parameters (purity, viable cell density, viability, osmolality) were evaluated in this analysis. Score plots, loadings plots, and VIP plots were utilized for assessing scale-up and comparability of the cell-culture process. Batch control charts were found to be useful for fault diagnosis during routine manufacturing. Finally, observations made from reviewing VIP plots were found to be in agreement with conclusions from process characterization studies demonstrating the effectiveness of MVDA as a tool for extracting process knowledge. PMID- 17269673 TI - Modeling of purification operations in biotechnology: enabling process development, optimization, and scale-up. AB - Process modeling involves the use of a set of mathematical equations to represent key physical phenomena involved in the process. An appropriately validated model can be used to predict process behavior with limited experimental data, identify critical ranges for process variables, and guide further process development. Although process modeling is extensively used in the chemical process industries, it has not been widely used in purification unit operations in biotechnology. Recent FDA guidelines encourage the use of process modeling during process development, along with multivariate statistical methods, detailed risk assessment, and other quantifiers of uncertainty. This paper will review recent advances in the modeling of key downstream unit operations: chromatography, filtration, and centrifugation. The focus will be on the application of modeling for industrial applications. Relevant papers presented at a session on this topic at the recent American Chemical Society National Meeting in San Francisco will also be reviewed. PMID- 17269674 TI - Substrate supply for effective biocatalysis. AB - Using biocatalysis for some chemical synthesis steps has unique advantages such as achieving higher product selectivity under ambient process conditions. However, a common limitation with such systems is the inhibition or toxicity posed by the starting substrate as well as limited aqueous solubility in many cases. In this review, we discuss the supply of substrate to bioconversions. The delivery of substrate via an auxiliary, which may be water-miscible, or a second phase such as a water-immiscible organic solvent, adsorbing resin, or a gas, is examined through recent examples in the field. Finally, guidelines for experimental planning and process considerations are suggested to facilitate the choice of substrate delivery method and accelerate process development. PMID- 17269675 TI - On the matching and proportional laws of cybernetic models. AB - The Matching and Proportional Laws are heuristic control policies that have found widespread use in cybernetic models of biological systems. Within this context, the laws serve as optimization surrogates for predicting the response of metabolic control circuits that modulate enzyme levels and activities. The key result of the current contribution is to demonstrate clearly the optimality properties of these laws and the assumptions that underlie their development. In doing so, we arrive at generalized versions of the Matching and Proportional Laws that are shown to collapse to the forms originally derived by Kompala et al. (Biotechnol. Bioeng. 1986, 28, 1044-1055) when certain simplifications are applied. As a further line of investigation, we show how Kompala et al.'s cybernetic laws compare with alternative control policies in their ability to describe diauxic growth behavior of microbial cultures. We find that Kompala et al.'s model describes the experimental observations more accurately than other limiting-case models that are either too aggressive or too passive in capturing the mixed-substrate growth rates and intermediate lag periods. Monte Carlo analysis of computational growth experiments in which strains obeying different regulatory policies directly compete for available nutrients reveals that the Matching and Proportional Law policy does not maximize the average growth rate of the culture. However, it allocates metabolic resources more frugally than other policies that outperform it and may be more realistic in reflecting the cell's true fitness-to-cost tradeoff as judged by its agreement with experimental growth data. PMID- 17269676 TI - Enzymatic hydrolysis of wheat arabinoxylan by a recombinant "minimal" enzyme cocktail containing beta-xylosidase and novel endo-1,4-beta-xylanase and alpha-l arabinofuranosidase activities. AB - This study describes the identification of the key enzyme activities required in a "minimal" enzyme cocktail able to catalyze hydrolysis of water-soluble and water-insoluble wheat arabinoxylan and whole vinasse, a fermentation effluent resulting from industrial ethanol manufacture from wheat. The optimal arabinose releasing and xylan-depolymerizing enzyme activities were identified from data obtained when selected, recombinant enzymes were systematically supplemented to the different arabinoxylan substrates in mixtures; this examination revealed three novel alpha-l-arabinofuranosidase activities: (i) one GH51 enzyme from Meripilus giganteus and (ii) one GH51 enzyme from Humicola insolens, both able to catalyze arabinose release from singly substituted xylose; and (iii) one GH43 enzyme from H. insolens able to catalyze the release of arabinose from doubly substituted xylose. Treatment of water-soluble and water-insoluble wheat arabinoxylan with an enzyme cocktail containing a 20%:20%:20%:40% mixture and a 25%:25%:25%:25% mixture, respectively, of the GH43 alpha-l-arabinofuranosidase from H. insolens (Abf II), the GH51 alpha-l-arabinofuranosidase from M. giganteus (Abf III), a GH10 endo-1,4-beta-xylanase from H. insolens (Xyl III), and a GH3 beta-xylosidase from Trichoderma reesei (beta-xyl) released 322 mg of arabinose and 512 mg of xylose per gram of water-soluble wheat arabinoxylan dry matter and 150 mg of arabinose and 266 mg of xylose per gram of water-insoluble wheat arabinoxylan dry matter after 24 h at pH 5, 50 degrees C. A 10%:40%:50% mixture of Abf II, Abf III, and beta-xyl released 56 mg of arabinose and 91 mg of xylose per gram of vinasse dry matter after 24 h at pH 5, 50 degrees C. The optimal dosages of the "minimal" enzyme cocktails were determined to be 0.4, 0.3, and 0.2 g enzyme protein per kilogram of substrate dry matter for the water-soluble wheat arabinoxylan, the water-insoluble wheat arabinoxylan, and the vinasse, respectively. These enzyme protein dosage levels were approximately 14, approximately 18, and approximately 27 times lower than the dosages used previously, when the same wheat arabinoxylan substrates were hydrolyzed with a combination of Ultraflo L and Celluclast 1.5 L, two commercially available enzyme preparations produced by H. insolens and T. reesei. PMID- 17269677 TI - Characterization of lipase in reversed micelles formulated with cibacron blue F 3GA modified span 85. AB - Sorbitan trioleate (Span 85) modified by Cibacron Blue F-3GA (CB) was prepared and used as an affinity surfactant to formulate a reversed micellar system for Candida rugosa lipase (CRL) solubilization. The system was characterized and evaluated by employing CRL-catalyzed hydrolysis of olive oil as a model reaction. The micellar hydrodynamic radius results reflected, to some extent, the redistribution of surfactant and water after enzyme addition, and the correlation between surfactant formulation, water content (W0), micellar size, and enzyme activity. An adequate modification density of CB was found to be important for the reversed micelles to retain enough hydration capacity and achieve high enzyme activity. Compared with the results in AOT-based reversed micelles, CRL in this micellar system exhibited a different activity behavior versus W0. The optimal pH and temperature of the encapsulated lipase remained unchanged, but the apparent activity was significantly higher than that of the native enzyme in bulk solution. Kinetic studies indicated that the encapsulated lipase in the reversed micelles of CB-formulated Span 85 followed the Michaelis-Menten equation. The Michaelis constant was found to decrease with increasing surfactant concentration, suggesting an increase of the enzyme affinity for the substrate. Stability of the lipase in the reversed micelles was negatively correlated to W0. PMID- 17269678 TI - Biomimetic catalysis for hemicellulose hydrolysis in corn stover. AB - Efficient and economical hydrolysis of plant cell wall polysaccharides into monomeric sugars is a significant technical hurdle in biomass processing for renewable fuels and chemicals. One possible approach to overcoming this hurdle is a biomimetic approach with dicarboxylic acid catalyst mimicking the catalytic core microenvironment in natural enzymes. This paper reports developments in the use of a dicarboxylic acid catalyst, maleic acid, for hemicellulose hydrolysis in corn stover. Hemicellulose hydrolysis and xylose degradation kinetics in the presence of maleic acid was compared to sulfuric acid. At optimized reaction conditions for each acid, maleic acid hydrolysis results in minimal xylose degradation, whereas sulfuric acid causes 3-10 times more xylose degradation. These results formed the basis for optimizing the hydrolysis of hemicellulose from corn stover using maleic acid. At 40 g/L dry corn stover solid-loading, both acid catalysts can achieve near-quantitative monomeric xylose yield. At higher solids loadings (150-200 g dry stover per liter), sulfuric acid catalyzed hydrolysis results in more than 30% degradation of the xylose, even under the previously reported optimal condition. However, as a result of minimized xylose degradation, optimized biomimetic hydrolysis of hemicellulose by maleic acid can reach approximately 95% monomeric xylose yields with trace amounts of furfural. Fermentation of the resulting unconditioned hydrolysate by recombinant S. cerevisiae results in 87% of theoretical ethanol yield. Enzyme digestibility experiments on the residual corn stover solids show that >90% yields of glucose can be produced in 160 h from the remaining cellulose with cellulases (15 FPU/g glucan). PMID- 17269679 TI - Hydrogen production by photoreactive nanoporous latex coatings of nongrowing Rhodopseudomonas palustris CGA009. AB - Nonuniform light distribution is a fundamental limitation to biological hydrogen production by phototrophic bacteria. Numerous light distribution designs and culture conditions have been developed to reduce self-shading and nonuniform reactivity within bioreactors. In this study, highly concentrated (2.0 x 108 CFU/muL formulation) nongrowing Rhodopseudomonas palustris CGA009 were immobilized in thin, nanoporous, latex coatings. The coatings were used to study hydrogen production in an argon atmosphere as a function of coating composition, thickness, and light intensity. These coatings can be generated aerobically or anaerobically and are more reactive than an equivalent number of suspended or settled cells. Rhodopseudomonas palustris latex coatings remained active after hydrated storage for greater than 3 months in the dark and over 1 year when stored at -80 degrees C. The initial hydrogen production rate of the microphotobioreactors containing 6.25 cm2, 58.4 mum thick Rps. palustris latex coatings illuminated by 34.1 PAR mumol photons m-2 s-1 was 6.3 mmol H2 m-2 h-1 and had a final yield of 0.55 mol H2 m-2 in 120 h. A dispersible latex blend has been developed for direct comparison of the specific activity of settled, suspended, and immobilized Rps. palustris. PMID- 17269680 TI - A novel porphyrin-based photocatalytic system for terpenoids production from (R) (+)-limonene. AB - A porphyrin-based photoexcited system has been revealed to be an efficient catalyst for d-limonene biotransformation under mild conditions and using molecular oxygen or/and H2O2 as oxidants. The influence of the oxidant, the wavelength of visible light, and the photoexcitation time on the catalytic system were studied for limonene oxidation with 5,10,15,20-tetraphenylporphyrin (H2TPP) as a catalyst. This porphyrin-catalyzed oxidation of limonene to three main products identified as carvone, an unknown product with a verbenone-like mass spectrum (1), and a (1S,4R)-p-mentha-2,8-diene 1-hydroperoxide (2). The highest conversion yield of these products was achieved at a very high molar ratio of H2TPP to limonene. The dependence of the biotransformation yield on the kind of solvent with different acceptor/donor electron properties was also investigated. Ethyl alcohol proved to be the best among the considered additives used for the reaction. Limonene photooxidation was not significantly dependent on wavelengths of visible light. It was concluded by UV-vis experiments that the reaction proceeds via a free-radical or/and molecular mechanism. Additional evidence for its radical nature was obtained from reactivity investigations. Maximal yield of carvone was obtained in the medium containing 90% of the substrate, within the period of 18 to 36 h of exposition to sunlight. PMID- 17269681 TI - Generation of reactive oxygen and antioxidant species by hydrodynamically stressed suspensions of Morinda citrifolia. AB - The generation of reactive oxygen species (ROS) by plant cell suspension cultures, in response to the imposition of both biotic and abiotic stress, is well-documented. This study investigated the generation of hydrogen peroxide by hydrodynamically stressed cultures of Morinda citrifolia, over a 5-h period post stress imposition. Suspensions were exposed to repeated passages through a syringe, under laminar flow conditions, corresponding to cumulative energy dissipation levels of approximately 3-6 J kg-1. Extracellular hydrogen peroxide was detected using a luminol-based chemiluminescence assay. The addition of exogenous hydrogen peroxide facilitated the detection of low levels of hydrogen peroxide in the presence of antioxidants. Immediately after shear exposure, there was evidence of significant antioxidative capacity in the sheared cell cultures, which potentially masked any oxidative burst (OB), but which decreased over the following 40 min. This antioxidative capacity was determined to derive from the shearing process. Trials in which ground cellular debris was added to control suspensions suggested that some of the antioxidative capacity observed in stressed suspensions was directly associated with debris generated by the shearing process. Using UV-vis spectrophotometry and HPLC, stress-related increases in the levels of phenolic compounds were detected in suspension filtrates. Under the stress conditions investigated, maximum hydrogen peroxide levels of 11.5 muM were observed, 5 h after shear exposure. This study emphasizes the importance of considering both oxidative and antioxidative capacities as part of a holistic approach to the determination of the OB in hydrodynamically stressed plant cell suspension cultures. PMID- 17269682 TI - Single-step purification of recombinant Thermus aquaticus DNA polymerase using DNA-aptamer immobilized novel affinity magnetic beads. AB - A DNA aptamer specific for Thermus aquaticus DNA polymerase (Taq-polymerase) was immobilized on magnetic beads, which were prepared in the presented study. The effect of various parameters including pH, temperaturem and aptamer concentration on the immobilization of 5'-thiol labeled DNA-aptamer onto glutaric dialdhyde activated magnetic beads was evaluated. The binding conditions of Taq-polymerase on the aptamer immobilized magnetic beads were studied using commercial Taq polymerase to characterize the surface complexation reaction. Efficiency of affinity magnetic beads in the purification of recombinant Taq-polymerase from crude extracts was also evaluated. For this case, the enzyme "recombinant Taq-DNA polymerase" was cloned and expressed using an Amersham E. coli GST-Gene Fusion Expression system. Crude extracts were in contact with affinity magnetic beads for 30 min and were collected by magnetic field application. The purity of the eluted Tag-polymerase from the affinity beads, as determined by HPLC, was 93% with a recovery of 89% in a one-step purification protocol. Apparently, the system was found highly effective as one step for the low-cost purification of Taq-polymerase in bacterial crude extract. PMID- 17269683 TI - Stabilities and conformational transitions of various proteases in the presence of an organic solvent. AB - The half-life of the activity of the PST-01 protease that was secreted by organic solvent-tolerant Pseudomonas aeruginosa PST-01 was very long in the presence of methanol as compared to that in the absence of methanol. The conformational transitions of the PST-01 protease, alpha-chymotrypsin, thermolysin, and subtilisin in the presence and absence of methanol were monitored by measuring the CD spectra. The conformational stabilities of the PST-01 protease and subtilisin in the presence of methanol were higher than those in the absence of methanol. This resulted in high stability of these proteases in the presence of methanol. Furthermore, it was suggested that the organic solvent stabilities of enzymes were closely related to the secondary structure by monitoring the conformational transitions of polyamino acids, which form the particular conformations, in the presence and absence of methanol. PMID- 17269684 TI - Target control of cell disruption to minimize the biomass electrostatic adhesion during anion-exchange expanded bed adsorption. AB - Expanded bed adsorption (EBA) is an integrative unit operation for the primary recovery of bioproducts from crude feedstock. Biomass electrostatic adhesion often leads to bad bed stability and low adsorption capacity. The results indicate that effective cell disruption is a potential approach to reduce the biomass adhesion during anion-exchange EBA. Two common cell disruption methods (sonication treatment and high-pressure disruption with a French press) were investigated in the present work. The mean size of cell debris reduced dramatically during the cell disruption process, and the absolute value of the zeta potential of cell debris also decreased significantly as the mean size reduced. The biomass transmission index (BTI) obtained through the biomass pulse response experiment was used to quantitatively evaluate the biomass-adsorbent interaction. Combining the influences of zeta potential of adsorbent (zetaA), zeta potential of biomass (zetaB), and biomass mean size (dB), the parameter of ( zetaA.zetaB.dB) was explored as a reasonable indicator of biomass adhesion in expanded beds. A good linear correlation was confirmed between BTI and ( zetaA.zetaB.dB) for all biomass and cell disruption conditions tested, which was independent of the cell disruption methods. A target parameter (-zetaA.zetaB.dB) of 120 mV2mum was derived for BTI above 0.9, which meant a very slight influence of biomass on the stability of the expanded bed. This criterion could be used as a rational control target for cell disruption processes in EBA applications. PMID- 17269685 TI - Dynamic metabolic modeling for a MAB bioprocess. AB - Production of monoclonal antibodies (MAb) for diagnostic or therapeutic applications has become an important task in the pharmaceutical industry. The efficiency of high-density reactor systems can be potentially increased by model based design and control strategies. Therefore, a reliable kinetic model for cell metabolism is required. A systematic procedure based on metabolic modeling is used to model nutrient uptake and key product formation in a MAb bioprocess during both the growth and post-growth phases. The approach combines the key advantages of stoichiometric and kinetic models into a complete metabolic network while integrating the regulation and control of cellular activity. This modeling procedure can be easily applied to any cell line during both the cell growth and post-growth phases. Quadratic programming (QP) has been identified as a suitable method to solve the underdetermined constrained problem related to model parameter identification. The approach is illustrated for the case of murine hybridoma cells cultivated in stirred spinners. PMID- 17269686 TI - Fabrication of artificial endothelialized tubes with predetermined three dimensional configuration from flexible cell-enclosing alginate fibers. AB - One possible strategy for creating three-dimensional (3D) tissue-engineered organs in vitro is to develop a vasculature for sufficient transport of oxygen and nutrients within these constructs. Here, we describe a novel technique to fabricate endothelialized tubes with predetermined 3D configuration, as a starting point for self-developing capillary-like networks in vitro. Calcium alginate hydrogel fibers of ca. 250 and 500 mum in diameter, enclosing bovine carotid artery vascular endothelial cells (BECs), were used as templates for endothelialized tubes. Fibers were prepared by extruding a 2% (w/v) sodium alginate solution containing BECs into a 100 mM calcium chloride solution flowing in the same direction. Fibers were embedded in type I collagen gels and enzymatically degraded by alginate lyase, resulting in channels with predetermined 3D configuration filled with a BEC suspension. Cells attached to and covered the surfaces of the channels. Exposing the cells to medium containing basic fibroblast growth factor resulted in their migration into the ambient collagen gel and self-assembly into capillary-like structures. These results demonstrate that using artificial endothelialized tubes with predetermined 3D configuration, as a starting point for a self-developing capillary-like network, could be potentially useful for constructing 3D tissue-engineered organs. PMID- 17269687 TI - A microcarrier-based cultivation system for expansion of primary mesenchymal stem cells. AB - Microcarrier cultures have been shown to allow extensive cell expansion of tissue engineering relevant cells, such as chondrocytes, while maintaining their phenotype. Our aim was to investigate the in vitro three-dimensional expansion of porcine bone-marrow-derived primary mesenchymal stem cells (MSC) using commercially available Cytodex type 1, type 2, and type 3 microcarriers. In comparison, the Cytodex type 1 microcarriers showed the best results for adherence with over 80% adherent cells after 3 h of incubation, analyzed by the Poisson distribution. Different start cell densities ranging from 1 to 3 x 106 cells per 100 cm2 had only a minor influence on adhesion. The proliferation was examined on Cytodex type 1 microcarriers over a cultivation time of 28 days, which could reveal cell growth and proof of cells recolonizing freshly added microcarriers. Scanning electron microscopy displayed appropriate cell morphology and confirmed cell proliferation. After enzymatic harvest from microcarriers, the osteogenic and chondrogenic differentiation of these cells was induced and shown by relevant histochemistry, such as von Kossa and Alcian blue staining. Totaling the results, we have shown that the three-dimensional expansion of MSC on microcarriers represents a beneficial alternative to the conventional two dimensional monolayer cultivation method. PMID- 17269688 TI - Modeling shear damage to suspended CHO cells during cross-flow filtration. AB - A mathematical model is presented for predicting the shear-induced decrease in live cells occurring over time during tangential flow filtration. The model uses a cell death rate constant (K) and considers the effects of flow rate, solution viability, and filtration system volumes and dimensions. Single pass and recycle capillary experiments with solutions of high (93%), medium (87%), and low (70%) viability were run, where the maximum laminar shear stress ranged from 10- 300 Pa, to validate the model and determine cell death rate constants. The K values for the suspended CHO cells used in this research ranged from 0.06 to 12.5 s-1. These K values increased with shear stress, as expected, and also as the solution viability decreased. PMID- 17269689 TI - High-level recombinant protein production in CHO cells using an adenoviral vector and the cumate gene-switch. AB - To facilitate and accelerate the production of eukaryotic proteins with correct post-translational modifications, we have developed a protein production system based on the transduction of Chinese hamster ovary (CHO) cells using adenovirus vectors (AdVs). We have engineered a CHO cell line (CHO-cTA) that stably expresses the transactivator (cTA) of our newly developed cumate gene-switch transcription system. This cell line is adapted to suspension culture and can grow in serum-free and protein-free medium. To increase the transduction level of AdVs, we have also generated a cell line (CHO-cTA-CAR) that expresses additional amounts of the coxackievirus and adenovirus receptor (CAR) on its surface. Recombinant protein production was tested using an AdV carrying the secreted alkaline phosphatase (SEAP) under the control of the CR5 promoter, which is strongly and specifically activated by binding to cTA. The SEAP expression was linked to the expression of the green fluorescent protein (GFP) through an internal ribosome entry site (IRES) to facilitate titration of the AdV. We monitored SEAP expression on a daily basis for 9 days after transduction of CHO cTA and CHO-cTA-CAR using different quantities of AdVs at 37 and 30 degrees C. Incubation at the latter temperature increased the production of SEAP at least 10 fold, and the presence of CAR increased the transduction level of the AdV. Maximum SEAP production (63 mg/L) was achieved at 6-7 days post-infection at 30 degrees C by transducing CHO-cTA-CAR with 500 infectious particles/cell. Because numerous AdVs can now be generated within a few weeks and large-scale production of AdVs is now a routine procedure, this system could be used to produce rapidly milligram quantities of a battery of recombinant proteins as well as for large scale protein production. PMID- 17269690 TI - Micropatterned biopolymer 3D scaffold for static and dynamic culture of human fibroblasts. AB - During in vivo tissue regeneration, cell behavior is highly influenced by the surrounding environment. Thus, the choice of scaffold material and its microstructure is one of the fundamental steps for a successful in vitro culture. An efficacious method for scaffold fabrication should prove its versatility and the possibility of controlling micro- and nanostructure. In this paper, hyaluronic acid 3D scaffolds were developed through lamination of micropatterned membranes, fabricated after optimization of a soft-lithography method. The scaffold presented here is characterized by a homogeneous hexagonal lattice with porosity of 69%, specific surface area of 287 cm-1, and permeability of 18.9 microm2. The control over the geometry was achieved with an accuracy of 20 mum. This technique allowed not only fabrication of planar 3D scaffolds but also production of thin wall tubular constructs. Mechanical tests, performed on dry tubular scaffolds, show high rupture tensile strength. This construct could be promising not only as engineered vascular grafts but also for regeneration of skin, urethra, and intestinal walls. The biocompatibility of a 3D planar scaffold was tested by seeding human fibroblasts. The cells were cultured in both static and dynamic conditions, in a perfusion bioreactor at different flow rates. Microscope analysis and MTT test showed cell proliferation and viability and a uniform cell distribution likely due to an appropriate lattice structure. PMID- 17269691 TI - Fractional factorial design for optimization of the SELDI protocol for human adipose tissue culture media. AB - The early factors inducing insulin resistance are not known. Therefore, we are interested in studying the secretome of the human visceral adipose tissue as a potential source of unknown peptides and proteins inducing insulin resistance. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry is a high-throughput proteomics technology to generate peptide and protein profiles (MS spectra). To obtain good quality and reproducible data from SELDI-TOF, many factors in the sample pretreatment and SELDI protocol should be optimized. To identify the optimal combination of factors resulting in the best and the most reproducible spectra, we designed an experiment where factors were varied systematically according to a fractional factorial design. In this study, seven protein chip preparation protocol factors were tested in 32 experiments. The main effects of these factors and their interactions contributing to the best quality spectra were identified by ANOVA. To assess the reproducibility, in a subsequent experiment the eight protocols generating the highest quality spectra were applied to samples in quadruplicates on different chips. This approach resulted in the development of an improved chip protocol, yielding higher quality peaks and more reproducible spectra. PMID- 17269692 TI - High-level production of a monoclonal antibody in murine myeloma cells by perfusion culture using a gravity settler. AB - A perfusion system is described for the production of a human monoclonal antibody in non-secreting murine myeloma (NS0) cells that was previously shown to be difficult to produce at high levels using fed-batch culture. The perfusion system was based on the use of a commercially available cell settler as the separation device to separate the cells from the culture. Separation efficiency of the cell settler was above 98%. Based on the growth and glucose consumption rates, fresh media was added to the culture and the turnover rate for the bioreactor was set at a maximum of 1.5 times the bioreactor volume per day. The perfusion process resulted in twice the maximum viable cell densities and up to three times the total protein production in a 53-day run period when compared to the fed-batch process. In addition, charge heterogeneity of the antibody as measured by ion exchange chromatography was lower for material purified from the perfusion runs compared to fed-batch. Perfusion mode of culture using a commercially available gravity settler is therefore a viable alternative to fed-batch mode for high level production of this monoclonal antibody in NS0 cells. PMID- 17269693 TI - Folate receptor targeted delivery of polyelectrolyte complex micelles prepared from ODN-PEG-folate conjugate and cationic lipids. AB - A polyelectrolyte complex micelle (PECM)-based delivery system for targeting folate (FOL) receptor overexpressing tumor cells is demonstrated using poly(ethylene glycol) (PEG)-conjugated oligonucleotide (ODN). The tumor targeting property was conferred to the PECM by tethering a folate moiety to the distal end of the PEG segment in an anti-sense green fluorescent protein (GFP) ODN-PEG conjugate. Nanoscale PECMs were spontaneously produced from ionic interactions between the ODN-PEG-FOL conjugate and a cationic lipid, lipofectamine (Lf). When treated with FOL receptor overexpressing cells (KB), the PCEMs caused a significant reduction in GFP expression in a dose-dependent manner. This effect was not observed in FOL receptor deficient cells (A549). The enhanced transfection of ODN-PEG-FOL/Lf PECMs to KB cells was caused by FOL receptor mediated endocytosis. The efficiency of target-specific gene suppression by ODN PEG-FOL/Lf PECMs was maintained even in the presence of 10% fetal bovine serum in the transfection medium. PMID- 17269694 TI - Effects of gel concentration, human fibronectin, and cation supplement on the tissue-engineered cartilage. AB - Cultivation of bovine knee chondrocytes (BKCs) in various cationic additives was studied using chitosan-gelatin scaffolds, whose surfaces were modified by human fibronectin (HFN). Here, the genipin-crosslinked scaffolds were fabricated by the freezing/lyophilization method with various concentrations of the precursory gels. The experimental results indicated that a lower freezing temperature led to higher moisture content, porosity, and specific surface area of a scaffold. The higher the precursor concentration, the larger the moisture content of a scaffold. A fast biodegradation of scaffold matrix was generated by a high porosity with BKCs. A higher concentration of HFN coated on scaffold surfaces yielded a faster rate of BKC attachment from the culture medium. The amounts of BKCs, glycosaminoglycans, and collagen over 28-day cultivation increased with the scaffold porosity, the coating concentration of HFN, the seeding density of BKCs, and the calcium concentration in medium. PMID- 17269695 TI - Insights into the conformational changes of several human lysozyme variants associated with hereditary systemic amyloidosis. AB - In this study, various ethanol- and temperature-induced molecular dynamics simulations were conducted to investigate the conformational changes of several human lysozyme variants (I56T, D67H, and T70N) associated with hereditary systemic amyloidosis. The results show that these variants are all more sensitive to conditions affecting the structural integrity of this protein. The structural analyses of these variants reveal a high population of more unstable beta-domain and distorted hydrophobic core compared to the wild-type human lysozyme, particularly for the two natural amyloidogenic variants D67H and I56T. For the D67H variant, the distance between the mass centers of residues 54 and 67 was found to elongate as a result of the destruction of the hydrogen-bonding network stabilizing the two long loops in the beta-domain. It further accelerates the unfolding of this variant, starting from the hydrophobic core between the alpha- and beta-domains. For the I56T variant, the introduction of a hydrophilic residue in the hydrophobic core directly destroys the native contacts in the alpha-beta interface, leading to fast unfolding. The present results are consistent with the previous hypothesis suggesting that the distortion of the hydrophobic core at the alpha-beta interface putatively results in the formation of the initial "seed" for amyloid fibrils. PMID- 17269696 TI - Perfusion culture of hybridoma cells for hyperproduction of IgG(2a) monoclonal antibody in a wave bioreactor-perfusion culture system. AB - A novel wave bioreactor-perfusion culture system was developed for highly efficient production of monoclonal antibody IgG2a (mAb) by hybridoma cells. The system consists of a wave bioreactor, a floating membrane cell-retention filter, and a weight-based perfusion controller. A polyethylene membrane filter with a pore size of 7 microm was floating on the surface of the culture broth for cell retention, eliminating the need for traditional pump around flow loops and external cell separators. A weight-based perfusion controller was designed to balance the medium renewal rate and the harvest rate during perfusion culture. BD Cell mAb Medium (BD Biosciences, CA) was identified to be the optimal basal medium for mAb production during batch culture. A control strategy for perfusion rate (volume of fresh medium/working volume of reactor/day, vvd) was identified as a key factor affecting cell growth and mAb accumulation during perfusion culture, and the optimal control strategy was increasing perfusion rate by 0.15 vvd per day. Average specific mAb production rate was linearly corrected with increasing perfusion rate within the range of investigation. The maximum viable cell density reached 22.3 x 105 and 200.5 x 105 cells/mL in the batch and perfusion culture, respectively, while the corresponding maximum mAb concentration reached 182.4 and 463.6 mg/L and the corresponding maximum total mAb amount was 182.4 and 1406.5 mg, respectively. Not only the yield of viable cell per liter of medium (32.9 x 105 cells/mL per liter medium) and the mAb yield per liter of medium (230.6 mg/L medium) but also the mAb volumetric productivity (33.1 mg/L.day) in perfusion culture were much higher than those (i.e., 22.3 x 105 cells/mL per liter medium, 182.4 mg/L medium, and 20.3 mg/L.day) in batch culture. Relatively fast cell growth and the perfusion culture approach warrant that high biomass and mAb productivity may be obtained in such a novel perfusion culture system (1 L working volume), which offers an alternative approach for producing gram quantity of proteins from industrial cell lines in a liter-size cell culture. The fundamental information obtained in this study may be useful for perfusion culture of hybridoma cells on a large scale. PMID- 17269698 TI - Engineering of PHB synthesis causes improved elastic properties of flax fibers. AB - Flax stem is a source of fiber used by the textile industry. Flax fibers are separated from other parts of stems in the process called retting and are probably the first plant fibers used by man for textile purposes (1). Nowadays flax cultivation is often limited because of its lower elastic property compared to cotton fibers. Thus the goal of this study was to increase the flax fiber quality using a transgenic approach. Expression of three bacterial genes coding for beta-ketothiolase (phb A), acetoacetyl-CoA reductase (phb B), and PHB synthase (phb C) resulted in poly-beta-hydroxybutyrate (PHB) accumulation in the plant stem. PHB is known as a biodegradable thermoplastic displaying chemical and physical properties similar to those of conventional plastics (i.e., polypropylene). The fibers isolated from transgenic flax plants cultivated in the field and synthesizing PHB were then studied for biomechanical properties. All measured parameters, strength, Young's modulus, and energy for failure of flax fibers, were significantly increased. Thus the substantial improvement in elastic properties of fibers from the transgenic line has been achieved. Since the acetyl CoA, substrate for PHB synthesis, is involved not only for energy production but also for synthesis of many cellular constituents, the goal of this study was also the analysis of those metabolites, which interfere with plant physiology and thus fiber quality. The analyzed plants showed that reduction in lignin, pectin, and hemicellulose levels resulted in increased retting efficiency. A significant increase in phenolic acids was also detected, and this was the reason for improved plant resistance to pathogen infection. However, a slight decrease in crop production was detected. PMID- 17269697 TI - Photolithographic patterning of C2C12 myotubes using vitronectin as growth substrate in serum-free medium. AB - The C2C12 cell line is frequently used as a model of skeletal muscle differentiation. In our serum-free defined culture system, differentiation of C2C12 cells into myotubes required surface-bound signals such as substrate adsorbed vitronectin or laminin. On the basis of this substrate requirement of myotube formation, we developed a photolithography-based method to pattern C2C12 myotubes, where myotubes formed exclusively on vitronectin surface patterns. We have determined that the optimal line width to form single myotubes is approximately 30 mum. To illustrate a possible application of this method, we patterned myotubes on the top of commercial substrate-embedded microelectrodes. In contrast to previous experiments where cell patterning was achieved by selective attachment of the cells to patterned surfaces in a medium that contained all of the factors necessary for differentiation, this study illustrates that surface patterning of a signaling molecule, which is essential for skeletal muscle differentiation in a defined system, can result in the formation of aligned myotubes on the patterns. This technique is being developed for applications in cell biology, tissue engineering, and robotics. PMID- 17269700 TI - Refolding and structural characteristic of TRAIL/Apo2L inclusion bodies from different specific growth rates of recombinant Escherichia coli. AB - TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) was produced mainly as inclusion bodies (IBs) by recombinant Escherichia coli with a temperature inducible expression system. The yield of TRAIL type 2 IBs at higher preinduction specific growth rate (mu = 0.15 h-1) was higher than that of TRAIL type 1 IBs at lower preinduction specific growth rate (mu = 0.05 h-1). With the same optimized refolding protocols, two types of IBs exhibited different refolding features. Refolded type 1 IBs had higher recovery of more than 80% compared with type 2 IBs (57-63%). By the measurements of fluorescence and CD spectroscopy, type 1 TRAIL IBs dissolved by urea appeared to be a closer secondary structure to the native TRAIL than type 2. Furthermore, with trypsin treatment, the striking decrease in stability of type 1 IBs against protease digestion cannot be attributed to their small size particles observed by scanning electron microscope and probably depend on different protein structure properties between the two IBs. Different properties of inclusion bodies were mainly influenced by different physiological states of the cells just prior to the induction. PMID- 17269701 TI - Electrochemical regeneration of NADH using conductive vanadia-silica xerogels. AB - Electrically conductive sol-gel matrices have been first introduced in order to enhance the efficiency of electrochemical NADH regeneration systems for biocatalysis. Vanadia-silica mixed gels as conductive sol-gels were synthesized using vanadium (V) oxytripropoxide (VOTP) and tetramethyl orthosilicate (TMOS) as precursors. Direct electrochemical reductions of NAD+ were carried out in the presence of vanadia-silica xerogels using unmodified platinum electrodes. Vanadia silica gels from higher ratios of VOTP to TMOS could effectively improve electrochemical generations of NADH from NAD+. Direct electrochemical regenerations of NADH were coupled to the synthesis of l-glutamate from alpha ketoglutarate catalyzed by glutamate dehydrogenases (GDH). In this case, vanadia silica gels were used as matrices for enzyme encapsulation, as opposed to serving as additives. When GDH were entrapped in "nonconductive" silica gels, synthesized using only TMOS, in the control experiment, the initial supply of NADH exhausted quickly and a final conversion of 30% was obtained. However, the use of conductive vanadia-silica gels with encapsulated GDH resulted in complete conversion of alpha-ketoglutarate to l-glutamate. A turnover number of a cofactor was also enhanced 3-fold by the application of conductive vanadia-silica gels. PMID- 17269699 TI - Self-assembled poly(butadiene)-b-poly(ethylene oxide) polymersomes as paclitaxel carriers. AB - In this work, self-assembled poly(butadiene)-b-poly(ethylene oxide) (PB-PEO) polymersomes (polymer vesicles) and worm micelles were evaluated as paclitaxel carriers. Paclitaxel was successfully incorporated into PB-PEO polymersomes and worm micelles. The loading capacity of paclitaxel inside PB-PEO colloids ranged from 6.7% to 13.7% w/w, depending on the morphology of copolymer colloids and the molecular weight of diblock copolymer. Paclitaxel loaded OB4 (PB219-PEO121) polymersome formulations were colloidally stable for 4 months at 4 degrees C and exhibited slow steady release of paclitaxel over a 5 week period at 37 degrees C. Evaluation of the in vitro cytotoxicity of paclitaxel-polymersome formulations showed that the ability of paclitaxel-loaded polymersomes to inhibit proliferation of MCF-7 human breast cancer cells was less compared to paclitaxel alone. By increasing the concentration of paclitaxel in polymersomes from 0.02 to 0.2 mug/mL, paclitaxel-polymersome formulations showed comparable activity in inhibiting the growth of MCF-7 cells. Taken together, these results demonstrate that paclitaxel-polymersomes have desirable restrained release profile and exhibit long-term stability. PMID- 17269702 TI - Analytical strategies in metabonomics. AB - To perform metabonomics investigations, it is necessary to generate comprehensive metabolite profiles for complex samples such as biofluids and tissue/tissue extracts. Analytical technologies that can be used to achieve this aim are constantly evolving, and new developments are changing the way in which such profiles' metabolite profiles can be generated. Here, the utility of various analytical techniques for global metabolite profiling, such as, e.g., 1H NMR, MS, HPLC-MS, and GC-MS, are explored and compared. PMID- 17269704 TI - Chemometrics in metabonomics. AB - We provide an overview of how the underlying philosophy of chemometrics is integrated throughout metabonomic studies. Four steps are demonstrated: (1) definition of the aim, (2) selection of objects, (3) sample preparation and characterization, and (4) evaluation of the collected data. This includes the tools applied for linear modeling, for example, Statistical Experimental Design (SED), Principal Component Analysis (PCA), Partial least-squares (PLS), Orthogonal-PLS (OPLS), and dynamic extensions thereof. This is illustrated by examples from the literature. PMID- 17269703 TI - From exogenous to endogenous: the inevitable imprint of mass spectrometry in metabolomics. AB - Mass spectrometry (MS) is an established technology in drug metabolite analysis and is now expanding into endogenous metabolite research. Its utility derives from its wide dynamic range, reproducible quantitative analysis, and the ability to analyze biofluids with extreme molecular complexity. The aims of developing mass spectrometry for metabolomics range from understanding basic biochemistry to biomarker discovery and the structural characterization of physiologically important metabolites. In this review, we will discuss the techniques involved in this exciting area and the current and future applications of this field. PMID- 17269705 TI - Analytical aspects of plant metabolite profiling platforms: current standings and future aims. AB - Over the past years, metabolic profiling has been established as a comprehensive systems biology tool. Mass spectrometry or NMR spectroscopy-based technology platforms combined with unsupervised or supervised multivariate statistical methodologies allow a deep insight into the complex metabolite patterns of plant derived samples. Within this review, we provide a thorough introduction to the analytical hard- and software requirements of metabolic profiling platforms. Methodological limitations are addressed, and the metabolic profiling workflow is exemplified by summarizing recent applications ranging from model systems to more applied topics. PMID- 17269706 TI - Tumour metabolomics in animal models of human cancer. AB - Multinuclear Nuclear Magnetic Resonance Spectroscopy (MRS) and mass spectrometry (MS) are the key analytical techniques used in an increasing manner to explore tumor metabolite profiles. Recent work has revealed that metabolite profiles in various tumor preparations (i.e., cultured cells, tissue specimens, and tumors in vivo) show strong correlations with tumor type, proliferation, metabolic activity, and cell death. These data are regarded as highly promising for tumor diagnosis as well as assessment of prognosis and treatment response in a clinical setting. In this pursuit, animal models of human cancer have played a central role. In this short account, we review the potentials of MRS and MS techniques for animal tumor metabolomic work, as well as highlight some interesting applications of these techniques for various animal tumor types. PMID- 17269707 TI - Proteomics approaches to study genetic and metabolic disorders. AB - Several proteomics approaches to study different aspects of genetic and metabolic diseases are presented. The choice of technique is strongly dependent on the biological question to be addressed and the availability and amount of sample. In general, there are three approaches that may be used to study genetic and metabolic diseases: protein profiling of complex biological samples, identification of affected proteins, or a functional proteomics approach to study protein interactions and function. PMID- 17269708 TI - Nutritional metabonomics: applications and perspectives. AB - Nowadays, nutrition focuses on improving health of individuals through diet. Current nutritional research aims at health promotion, disease prevention, and performance improvement. Modern analytical platforms allow the simultaneous measurement of multiple metabolites providing new insights in the understanding of the functionalities of cells and whole organisms. Metabonomics, "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modifications", provides a systems approach to understanding global metabolic regulations of organisms. This concept has arisen from various applications of NMR and MS spectroscopies to study the multicomponent metabolic composition of biological fluids, cells, and tissues. The generated metabolic profiles are processed by multivariate statistics to maximize the recovery of information to be correlated with well determined stimuli such as dietary intervention or with any phenotypic data or diet habits. Metabonomics is thus uniquely suited to assess metabolic responses to deficiencies or excesses of nutrients and bioactive components. Furthermore, metabonomics is used to characterize the metabolic phenotype of individuals integrating genetic polymorphism, metabolic interactions with commensal and symbiotic partners such as gut microflora, as well as environmental and behavioral factors including dietary preferences. This paper reports several experimental key aspects in nutritional metabonomics, reviews its applications employing targeted and holistic approach analysis for the study of the metabolic responses following dietary interventions. It also reports the assessment of intra- and inter-individual variability in animal and human populations. The potentialities of nutritional metabonomics for the discovery of new biomarkers and the characterization of metabolic phenotypes are discussed in a context of their possible utilizations for personalized nutrition to provide health maintenance at the individual level. PMID- 17269709 TI - Metabonomics in pharmaceutical discovery and development. AB - Metabonomics has emerged as a key technology in pharmaceutical discovery and development, evolving as the small molecule counterpart of transcriptomics and proteomics. In drug discovery laboratories, metabonomics aids in target identification, phenotyping, and the understanding of the biochemical basis of disease and toxicity. This review focuses on three areas where metabonomics is used in the industry: (1) analytical considerations, (2) chemometric and statistical concerns, and (3) biological aspects and applications. PMID- 17269710 TI - Environmental metabolomics: a SWOT analysis (strengths, weaknesses, opportunities, and threats). AB - Metabolomic approaches have the potential to make an exceptional contribution to understanding how chemicals and other environmental stressors can affect both human and environmental health. However, the application of metabolomics to environmental exposures, although getting underway, has not yet been extensively explored. This review will use a SWOT analysis model to discuss some of the strengths, weaknesses, opportunities, and threats that are apparent to an investigator venturing into this relatively new field. SWOT has been used extensively in business settings to uncover new outlooks and identify problems that would impede progress. The field of environmental metabolomics provides great opportunities for discovery, and this is recognized by a high level of interest in potential applications. However, understanding the biological consequence of environmental exposures can be confounded by inter- and intra individual differences. Metabolomic profiles can yield a plethora of data, the interpretation of which is complex and still being evaluated and researched. The development of the field will depend on the availability of technologies for data handling and that permit ready access metabolomic databases. Understanding the relevance of metabolomic endpoints to organism health vs adaptation vs variation is an important step in understanding what constitutes a substantive environmental threat. Metabolomic applications in reproductive research are discussed. Overall, the development of a comprehensive mechanistic-based interpretation of metabolomic changes offers the possibility of providing information that will significantly contribute to the protection of human health and the environment. PMID- 17269711 TI - Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. AB - Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) have a major impact on the health of individuals and populations. Accurate diagnosis of inflammatory bowel disease (IBD) at an early stage, and correct differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is important for optimum treatment and prognosis. We present here the first characterization of fecal extracts obtained from patients with CD and UC by employing a noninvasive metabonomics approach, which combines high resolution 1H NMR spectroscopy and multivariate pattern recognition techniques. The fecal extracts of both CD and UC patients were characterized by reduced levels of butyrate, acetate, methylamine, and trimethylamine in comparison with a control population, suggesting changes in the gut microbial community. Also, elevated quantities of amino acids were present in the feces from both disease groups, implying malabsorption caused by the inflammatory disease or an element of protein losing enteropathy. Metabolic differences in fecal profiles were more marked in the CD group in comparison with the control group, indicating that the inflammation caused by CD is more extensive in comparison with UC and involves the whole intestine. Furthermore, glycerol resonances were a dominant feature of fecal spectra from patients with CD but were present in much lower intensity in the control and UC groups. This work illustrates the potential of metabonomics to generate novel noninvasive diagnostics for gastrointestinal diseases and may further our understanding of disease mechanisms. PMID- 17269712 TI - Novel application of reversed-phase UPLC-oaTOF-MS for lipid analysis in complex biological mixtures: a new tool for lipidomics. AB - Ultra-Performance LC (UPLC) utilizing sub-2-mum porous stationary phase particles operating with high linear velocities at pressures >9000 psi was coupled with orthogonal acceleration time-of-flight (oaTOF) mass spectrometry and successfully employed for the rapid separation of lipids from complex matrices. The UPLC system produced information-rich chromatograms with typical measured peak widths of 3 s at peak base, generating peak capacities in excess of 200 in 10 min. Further UPLC coupled with MSE technology provided parent and fragment mass information of lipids in one chromatographic run, thus, providing an attractive alternative to current LC methods for targeted lipid analysis as well as lipidomic studies. PMID- 17269714 TI - Evaluation of endogenous plasma peptide extraction methods for mass spectrometric biomarker discovery. AB - Peptides have a role in the inflammatory response, tumor biology, and endocrine processes, presenting them as appealing biomarker candidates. However, peptide extraction efficacy for clinical profiling remains a pivotal technological challenge, as maximum coverage of the plasma peptidome is limited by a range of factors including the inherent complexity of human plasma and the lower concentration of peptides compared to abundant proteins. The aim of this study was to evaluate commonly employed peptide extraction methodologies in terms of total number of peptides detected and the mass range of peptides observed by MALDI. Despite showing coelution of proteins, solid-phase extraction (SPE) methods exhibited superior plasma peptide recovery than ultrafiltration, acetonitrile (ACN) precipitation, or size-exclusion chromatography methods under conditions employed in the study. Not surprisingly, in line with studies challenging the veracity of many peptide biomarker studies, the majority of identified peptides eluted from SPE methods corresponded to proteolytic truncations of the most abundant plasma proteins. The prefractionation of plasma with acetonitrile precipitation prior to SPE provided distinct ion signal profiles and is worthy of further study. In conclusion, this study favors the use of SPE in peptide extraction protocols for increased biomarker coverage and diversity from the plasma peptidome. PMID- 17269713 TI - Proteomic identification of biomarkers in the cerebrospinal fluid (CSF) of astrocytoma patients. AB - The monitoring of changes in the protein composition of the cerebrospinal fluid (CSF) can be used as a sensitive indicator of central nervous system (CNS) pathology, yet its systematic application to analysis of CNS neoplasia has been limited. There is a pressing need for both a better understanding of gliomagenesis and the development of reliable biomarkers of the disease. In this report, we used two proteomic techniques, two-dimensional gel electrophoresis (2 DE), and cleavable Isotope-Coded Affinity Tag (cICAT) to compare CSF proteomes to identify tumor- and grade-specific biomarkers in patients bearing brain tumors of differing histologies and grades. Retrospective analyses were performed on 60 samples derived from astrocytomas WHO grade II, III, and IV, schwannomas, metastastic brain tumors, inflammatory samples, and non-neoplastic controls. We identified 103 potential tumor-specific markers of which 20 were high-grade astrocytoma-specific. These investigations allowed us to identify a spectrum of signature proteins that could be used to distinguish CSF derived from control patients versus those with low- (AII) or high-grade (AIV) astrocytoma. These proteins may represent new diagnostic, prognostic, and disease follow-up markers when used alone or in combination. These candidate biomarkers may also have functional properties that play a critical role in the development and malignant progression of human astrocytomas, thus possibly representing novel therapeutic targets for this highly lethal disease. PMID- 17269715 TI - Halothane binding proteome in human brain cortex. AB - Inhaled anesthetics bind specifically to a wide variety of proteins in the brain. This set of proteins must include those that contribute to the physiological and behavioral phenotypes of anesthesia and the related side effects. To identify the anesthetic-binding targets and functional pathways associated with these targets in human brain, halothane photolabeling and two-dimensional (2D) gel electrophoresis were used. Both membrane and soluble proteins from human temporal cortex were prepared. More than 300 membrane and 400 soluble protein spots were detected on the stained blots, of which 23 membrane and 34 soluble proteins were labeled by halothane and identified by mass spectroscopy. Their functional classification reveals five groups, including carbohydrate metabolism, protein folding, oxidative phosphorylation, nucleoside triphosphatase, and dimer/kinase activity with different correlative stringency. When network analysis of the interaction between these protein molecules is used, the weighted interaction accentuates the cellular protein components important in cell growth and proliferation, cell cycle and cell death, and cell-cell signaling and interactions, although no pathway was specific. This study provides evidence for multiple anesthetic binding targets and suggests potential pathways involved in their actions. PMID- 17269716 TI - Proteomic analysis of tyrosine phosphorylations in vascular endothelial growth factor- and reactive oxygen species-mediated signaling pathway. AB - Vascular endothelial growth factor (VEGF) mediates angiogenic signaling by activating tyrosine kinase receptors. Endothelial cells treated with VEGF are known to increase reactive oxygen species (ROS) production and activate the MAPK pathway. To identify the target proteins of the VEGF receptor, we treated human umbilical vein endothelial cells (HUVECs) with VEGF or H2O2, and identified and semiquantified tyrosine-phosphorylated proteins, combining 2D-gel electrophoresis, Western analysis using antibody against phospho-tyrosine, and mass spectrometry. We detected 95 proteins that were differentially phosphorylated; some were specifically phosphorylated by VEGF but not by H2O2. 2D gel electrophoresis revealed that heterogeneous populations of the same protein responded differently to H2O2 and VEGF. Bioinformatic studies examining the nature of the differential phosphorylation in various subpopulations of proteins should provide new insights into VEGF- and H2O2-induced signaling pathways. PMID- 17269717 TI - Proteomic profiling of intact proteins using WAX-RPLC 2-D separations and FTICR mass spectrometry. AB - We investigated the combination of weak anion exchange (WAX) fractionation and on line reversed-phase liquid chromatography (RPLC) separation using a 12 T FTICR mass spectrometer for the detection of intact proteins from a Shewanella oneidensis MR-1 cell lysate. This work aimed at optimizing intact protein detection for profiling proteins at a level that incorporates their modification state. A total of 715 intact proteins were detected, and the combined results from the WAX fractions and the unfractionated cell lysate were aligned using LC MS features to facilitate protein abundance measurements. Protein identifications and post-translational modifications were assigned for approximately 10% of the detected proteins by comparing intact protein mass measurements to proteins identified in peptide MS/MS analysis of an aliquot of the same fraction. Intact proteins were also detected for S. oneidensis lysates obtained from cells grown on 13C-, 15N-depleted media under aerobic and sub-oxic conditions. The strategy can be readily applied for measuring differential protein abundances and provides a platform for high-throughput selection of biologically relevant targets for further characterization. PMID- 17269718 TI - Interaction simulation of hERG K+ channel with its specific BeKm-1 peptide: insights into the selectivity of molecular recognition. AB - Potassium channels show a huge variability in the affinity when recognizing enormous bioactive peptides, and the elucidation of their recognition mechanism remains a great challenge due to an undetermined peptide-channel complex structure. Here, we employed combined computation methods to study the specific binding of BeKm-1 peptide to the hERG potassium channel, which is an essential determinant of the long-QT syndrome. By the use of a segment-assembly homology modeling method, the closed-state hERG structure containing unusual longer S5P linker was successfully constructed. It has a "petunia" shape, while four "petals" of symmetrically distributed S5P segments always decentralize. Starting from the hERG and BeKm-1 structures, a considerably reasonable BeKm-1-hERG complex structure was then screened out and identified by protein-protein docking, molecular dynamics (MD) simulations, and calculation of relative binding free energies. The validity of this predicted complex was further assessed by computational alanine-scanning, with the results correlating reasonably well with experimental data. In the novel complex structure, four considerably flexible S5P linkers are far from the BeKm-1 peptide. The BeKm-1 mainly uses its helical region to associate the channel outer vestibule, except for the S5P linker region; however, structural analysis further implies this neutral pore region with wiggling S5P linker is highly beneficial to the binding of BeKm-1 with lower positive charges. The most critical Lys18 of BeKm-1 plugs its side chain into the channel selectivity filter, while the secondarily important Arg20 forms three hydrogen bonds with spatially neighboring residues in the hERG channel. Different from the classical peptide-K+ channel interaction mainly induced by electrostatic interaction, a synergetic effect of the electrostatic and van der Waals interactions was found to mediate the molecular recognition between BeKm-1 and the hERG channel. And this specific binding process is revealed to be a dynamic change of reduction of binding free energy and conformational rearrangement mainly in the interface of both BeKm-1 and the hERG channel. All these structural and energy features yield deep insights on the high selective binding mechanism of hERG-specific peptides, present a diversity of peptide-K+ channel interactions, and also provide important clues to further study structure function relationships of the hERG channel. PMID- 17269719 TI - An iTRAQ-based quantitative analysis to elaborate the proteomic response of Nostoc sp. PCC 7120 under N2 fixing conditions. AB - Nostoc sp. PCC 7120 is an oxygen-evolving photoautotrophic N2 fixing filamentous cyanobacterium. Upon nitrogen starvation, a range of processes are initiated, such as differentiation of the heterocysts, specific cells where N2 fixation takes place. We have characterized and quantified the proteome of the Nostoc sp. PCC 7120 wild-type strain grown under N2 fixing and non-N2 fixing conditions. To assess global proteome changes in response to environmental changes, measurements were made using the quantitative proteomics tool, iTRAQ, on a whole cell digest. From this approach, a total of 486 different proteins was accurately identified across 2 biological replicate experiments, where 226 identifications contained 2 or more distinct peptides. Results of metabolic regulation will be discussed to demonstrate that proteomics represents an important tool for the development of heterocystous cyanobacteria for future biological H2 production. PMID- 17269720 TI - A new fast method for nanoLC-MALDI-TOF/TOF-MS analysis using monolithic columns for peptide preconcentration and separation in proteomic studies. AB - A new fast method for identification and characterization of proteolytic digests of proteins by monolithic liquid chromatography coupled with mass spectrometry has been developed. The advantages of the monolithic columns are a high-pressure stability and low back pressure resulting in higher flow rates for capillary or nanosize columns simplifying the system handling. As was shown in several publications, such monolithic stationary phases are highly qualified for the analysis of peptides and proteins, but so far, only small volumes could be injected into the system, which might hamper the sample preparation leading to protein precipitation and partial loss of sample. To overcome the problem of small injection volumes, we established a system including a short monolithic trap column to allow preconcentration of the peptides. The injected sample is flushed at higher flow rates onto the trap column, bound to the stationary phase, and in this way concentrated in a few nanoliters before starting the separation. The expanded system was optimized and tested using different reference protein samples. Eluting peptides were detected by MALDI-TOF/TOF-MS and identified by database searching. The system is now a permanent part for proteome analysis in our lab, and as such, it was successfully applied for the detection of post translational modifications and the analysis of membrane proteins. One example for these analyses is also included in this paper. PMID- 17269721 TI - iTRAQ is a useful method to screen for membrane-bound proteins differentially expressed in human natural killer cell types. AB - We are interested in the biological as well as the molecular processes involved in natural killer (NK) cell development and function. Determining the proteomic complement could be a useful tool in predicting cellular function and fate. For the first time shown here, we have utilized iTRAQ, a new method that allows identification and quantification of proteins between multiple samples, to determine the expression of membrane-bound proteins in two previously characterized human NK cell populations. One population was derived from umbilical cord blood (UCB) stem cells (CD34+38-Lin-) and the other from expanded CD3-depleted adult peripheral blood. iTRAQ was employed for multiplex peptide labeling of proteins from fractionated membranes followed by two-dimensional high performance liquid chromatography (2D-HPLC), and tandem mass spectrometry was used to identify protein signatures. We were able to identify and quantify differences in expression levels of 400-800 proteins in a typical experiment. Ontology analysis showed the majority of the proteins to be involved in cell signaling, nucleic acid binding, or mitochondrial function. Nearly all proteins were associated with the plasma membrane, membrane-bound organelle (lysosome or mitochondria), or nucleus. We found several novel proteins highly expressed in UCB stem cell derived NK cells compared to adult NK cells including CD9, alpha-2 macroglobulin, brain abundant signaling protein (BASP1), and allograft inflammatory factor-1 (AIF-1). In addition, we were able to confirm several of our iTRAQ results by RT-PCR, Western blot, and fluorescence-activated cell sorting (FACS) analysis. This is the first demonstration and verification using iTRAQ to screen for membrane-bound protein differences in human NK cells and represents a powerful new tool in the field of proteomics. PMID- 17269722 TI - MyriMatch: highly accurate tandem mass spectral peptide identification by multivariate hypergeometric analysis. AB - Shotgun proteomics experiments are dependent upon database search engines to identify peptides from tandem mass spectra. Many of these algorithms score potential identifications by evaluating the number of fragment ions matched between each peptide sequence and an observed spectrum. These systems, however, generally do not distinguish between matching an intense peak and matching a minor peak. We have developed a statistical model to score peptide matches that is based upon the multivariate hypergeometric distribution. This scorer, part of the "MyriMatch" database search engine, places greater emphasis on matching intense peaks. The probability that the best match for each spectrum has occurred by random chance can be employed to separate correct matches from random ones. We evaluated this software on data sets from three different laboratories employing three different ion trap instruments. Employing a novel system for testing discrimination, we demonstrate that stratifying peaks into multiple intensity classes improves the discrimination of scoring. We compare MyriMatch results to those of Sequest and X!Tandem, revealing that it is capable of higher discrimination than either of these algorithms. When minimal peak filtering is employed, performance plummets for a scoring model that does not stratify matched peaks by intensity. On the other hand, we find that MyriMatch discrimination improves as more peaks are retained in each spectrum. MyriMatch also scales well to tandem mass spectra from high-resolution mass analyzers. These findings may indicate limitations for existing database search scorers that count matched peaks without differentiating them by intensity. This software and source code is available under Mozilla Public License at this URL: http://www.mc.vanderbilt.edu/msrc/bioinformatics/. PMID- 17269723 TI - Combination of abundant protein depletion and multi-lectin affinity chromatography (M-LAC) for plasma protein biomarker discovery. AB - We report on the development of a robust and relatively high-throughput method for in-depth proteomic analysis of human plasma suitable for biomarker discovery. The method consists of depletion of albumin and IgG and multi-lectin affinity chromatography (M-LAC), followed by nanoLC-MS/MS analysis of digested proteins and label-free comparative quantitation of proteins. The performance of the method is monitored by multiple quality control points to ensure reproducibility of the analysis. The method identifies proteins that are reported to be present in normal plasma at concentrations of 10-100 ng/mL and that may be of particular interest when studying a variety of disease conditions. Numerous tissue leakage proteins of potentially even lower concentrations are also identified. When the method was used in a study to identify potential biomarkers of psoriasis, the differential abundance of proteins present at low mug/mL level was quantitated and later verified by ELISA measurements. PMID- 17269725 TI - Two-dimensional fluorescence difference gel electrophoresis analysis of spermatogenesis in the rat. AB - The molecular mechanisms underlying normal and pathological spermatogenesis remain poorly understood. We compared protein concentrations in different germ cell types to identify those proteins specifically or preferentially expressed at each stage of rat spermatogenesis. Crude cytosolic protein extracts and reversed phase HPLC prefractionated cytosolic extracts from spermatogonia, pachytene spermatocytes, and early spermatids were subjected to two-dimensional difference gel electrophoresis (2-D DIGE). By comparing gels and carrying out statistical analyses, we were able to identify 1274 protein spots with relative abundances differing significantly between the three cell types. We found that 265 of these spots displaying highly differential expression (ratio > or = 2.5 between two cell types), identified by mass fingerprinting, corresponded to 123 nonredundant proteins. The proteins clustered into three clades, corresponding to mitotic, meiotic, and post-meiotic cell types. The differentially expressed proteins identified by 2-D DIGE were confirmed and validated by western blotting and immunohistochemistry, in the few cases in which antibodies were available. 2-D DIGE appears a relevant proteomics approach for studying rat germ cell differentiation, allowing the establishment of the precise expression profiles for a relatively large number of proteins during normal spermatogenesis. PMID- 17269726 TI - Identification of secreted proteins during skeletal muscle development. AB - The differentiation program of skeletal muscle cells is exquisitely sensitive to secreted proteins. We developed a strategy to maximize the discovery of secreted proteins, using mass spectrometry-based proteomics, from cultured muscle cells, C2C12, grown in a serum-free medium. This strategy led to the identification of 80 nonredundant proteins, of which 27 were secretory proteins that were identified with a minimum of two tryptic peptides. A number of the identified secretory proteins are involved in extracellular matrix remodeling, cellular proliferation, migration, and signaling. A putative network of proteins involving matrix metalloproteinase 2, SPARC, and cystatin C that all interact with TGFbeta signaling has been postulated to contribute toward a functional role in the myogenic differentiation program. PMID- 17269724 TI - Identification of cellular interaction partners of the influenza virus ribonucleoprotein complex and polymerase complex using proteomic-based approaches. AB - Cellular factors that associate with the influenza A viral ribonucleoprotein (vRNP) are presumed to play important roles in the viral life cycle. To date, interaction screens using individual vRNP components, such as the nucleoprotein or viral polymerase subunits, have revealed few cellular interaction partners. To improve this situation, we performed comprehensive, proteomics-based screens to identify cellular factors associated with the native vRNP and viral polymerase complexes. Reconstituted vRNPs were purified from human cells using Strep-tagged viral nucleoprotein (NP-Strep) as bait, and co-purified cellular factors were identified by mass spectrometry (MS). In parallel, reconstituted native influenza A polymerase complexes were isolated using tandem affinity purification (TAP) tagged polymerase subunits as bait, and co-purified cellular factors were again identified by MS. Using these techniques, we identified 41 proteins that co purified with NP-Strep-enriched vRNPs and four cellular proteins that co-purified with the viral polymerase complex. Two of the polymerase-associated factors, importin-beta3 and PARP-1, represent novel interaction partners. Most cellular proteins previously shown to interact with either viral NP and/or vRNP were also identified using our method, demonstrating its sensitivity. Co immunoprecipitation studies in virus-infected cells using selected novel interaction partners, including nucleophosmin (NPM), confirmed their association with vRNP. Immunofluorescence analysis further revealed that NPM is recruited to sites of viral transcription and replication in infected cells. Additionally, overexpression of NPM resulted in increased viral polymerase activity, indicating its role in viral RNA synthesis. In summary, the proteomics-based approaches used in this study represent powerful tools to identify novel vRNP-associated cellular factors for further characterization. PMID- 17269727 TI - Structural and functional analysis of hypothetical proteins in mouse hippocampus from two-dimensional gel electrophoresis. AB - Protein profiling in five individual mouse strains showed strain-specific expression of three hypothetical proteins (HPs). As functional and structural assignment of HPs were based on predictions and low identity to known structures, HPs were identified by MALDI-TOF/TOF, and their proposed tentative function was determined by enzyme assays. Three identified HPs were extracted from gels and renatured, and pyridoxal phosphate phosphatase, inorganic pyrophosphate phosphatase, and antioxidant activities were revealed, findings in agreement with functional predictions. PMID- 17269728 TI - Profiling the membrane proteome of Shewanella oneidensis MR-1 with new affinity labeling probes. AB - The membrane proteome plays a critical role in electron transport processes in Shewanella oneidensis MR-1, a bacterial organism that has great potential for bioremediation. Biotinylation of intact cells with subsequent affinity-enrichment has become a useful tool for characterization of the membrane proteome. As opposed to these commonly used, water-soluble commercial reagents, we here introduce a family of hydrophobic, cell-permeable affinity probes for extensive labeling and detection of membrane proteins. When applied to S. oneidensis cells, all three new chemical probes allowed identification of a substantial proportion of membrane proteins from total cell lysate without the use of specific membrane isolation method. From a total of 410 unique proteins identified, approximately 42% are cell envelope proteins that include outer membrane, periplasmic, and inner membrane proteins. This report demonstrates the first application of this intact cell biotinylation method to S. oneidensis and presents the results of many identified proteins that are involved in metal reduction processes. As a general labeling method, all chemical probes we introduced in this study can be extended to other organisms or cell types and will help expedite the characterization of membrane proteomes. PMID- 17269729 TI - Proteome analysis of serum from type 2 diabetics with nephropathy. AB - Diabetic nephropathy (DN) is a renal disease which develops as a consequence of diabetes mellitus. Microalbuminuria is the earliest clinical sign of DN. There are no specific diagnostic biomarkers for type 2 diabetics with nephropathy other than microalbuminuria and macroalbuminuria. However, microalbuminuria does not constitute a sole independent indicator for type 2 diabetics with nephropathy, and thus, another screening method, such as a biomarker assay, is required in order to diagnose it more correctly. Therefore, we have utilized two-dimensional electrophoresis (2-DE) to identify human serum protein markers for the more specific and accurate prediction of progressive nephropathy in type 2 diabetes patients, via comparisons of the serum proteome in three experimental groups: type 2 diabetes patients without microalbuminuria (DM, n = 30), with microalbuminuria (MA, n = 29), and with chronic renal failure (CRF, n = 31). As a result, proteins which were differentially expressed with statistical significance (p < 0.05) in MA and CRF groups as compared to those in DM group were selected and identified by ESI-Q-TOF MS/MS. Among these identified proteins, two proteins which might be useful as diagnostic biomarkers of type 2 diabetics with nephropathy were verified by Western blotting: extracellular glutathione peroxidase (eGPx) and apolipoprotein (ApoE) were found to exhibit a progressive reduction in MA and CRF groups. Notably, eGPx was further verified by ELISA using DM (n = 100) and MA (n = 96) patient samples. Collectively, our results show that the two proteins identified in this study may constitute potential biomarkers for the diagnosis of type 2 diabetics with nephropathy. PMID- 17269730 TI - Characterization of IQGAP1-containing complexes in NK-like cells: evidence for Rac 2 and RACK1 association during homotypic adhesion. AB - IQGAP1 is a scaffolding protein that binds to a diverse array of signaling and structural molecules that are often associated with cell polarization and adhesion. Through interaction with its target proteins, IQGAP1 participates in multiple cellular functions, including Ca2+-calmodulin signaling, definition of cytoskeletal architecture, regulation of Cdc42 and Rac1 dependent cytoskeletal changes, and control of E-cadherin mediated intercellular adhesion. These analysis have been largely restricted to cells of epithelial and fibroblast origin. The present studies were initiated to examine the role of IQGAP1 in cellular interactions involving the lymphoid cells. A mass spectrometric based analysis of IQGAP1 containing complexes isolated from the human NK-like cell line, YTS, identified several known and new potential IQGAP1 interaction partners including receptor of activated C kinase 1 (RACK1) and the small GTPase, Rac2. Immunofluorescence analysis of YTS cells indicated that a minor component of IQGAP1 was localized at the cell membrane with the remainder diffusely distributed through out the cytoplasm. However, at sites of cellular contact, there was a marked accumulation of IQGAP1. Staining for RACK1 and Rac2 revealed that both of these proteins accumulated these contact sites. Antibody-based studies suggested that a subset of RACK1 was associated in an IQGAP1-containing complex, which prevented recognition of RACK1 by monoclonal antibody. These results suggest that RACK1, Rac2, and IQGAP1 are components of complexes involved in NK cell homotypic adhesion. PMID- 17269731 TI - Identification of tumor antigens in human lung squamous carcinoma by serological proteome analysis. AB - Autoantibodies against tumor antigens are promising means for cancer diagnosis and prognosis. In this study, we applied a proteomic approach to identify proteins that commonly elicit humoral response in lung squamous carcinoma (LSC). Sera from 20 newly diagnosed patients with LSC and 20 matched healthy individuals were analyzed for antibody-based reactivity against LSC proteins separated by two dimensional electrophoresis. Autoantibodies against triosephosphate isomerase (Tim) and superoxide dismutase [Mn] (MnSOD) were detected in sera from over 20% patients with LSC but none from the normal controls. Furthermore, the occurrence of autoantibodies against Tim and MnSOD was evaluated by ELISA in an additional 40 LSC patients, 30 other types of cancer (OTC) patients, and 50 noncancer controls (NC). Results showed that frequency of autoantibody against Tim (27.5%) in LSC patients was significantly higher than that in OTC patients (6.7%, p = 0.027) and in NC (6%, p = 0.005). Likewise, frequency of autoantibody against MnSOD in LSC (20%) patients was significantly higher than that in NC (4%, p = 0.016), however, there was no significant difference when comparing to that in OTC patients (6.7%, p = 0.115). We also observed significantly increased expression and secretion of Tim and MnSOD in LSC, which possibly account for their autoantibody development. Our results indicate that autoantibody and antigen of Tim and MnSOD may be useful for screening and diagnosis of the lung squamous carcinoma. PMID- 17269733 TI - Identification of platinum-resistance associated proteins through proteomic analysis of human ovarian cancer cells and their platinum-resistant sublines. AB - Chemoresistance is a major therapeutic obstacle in cancer patients, and the mechanisms of drug resistance are not fully understood. In the present study, we established platinum-resistant human ovarian cancer cell lines and identified differentially expressed proteins related to platinum resistance. The total proteins of two sensitive (SKOV3 and A2780) and four resistant (SKOV3/CDDP, SKOV3/CBP, A2780/CDDP, and A2780/CBP) human ovarian cancer cell lines were isolated by two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were identified using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). In total, 57 differential protein spots were identified, and five proteins, including annexin A3, destrin, cofilin 1, Glutathione-S-transferase omega 1 (GSTO1-1), and cytosolic NADP+-dependent isocitrate dehydrogenase (IDHc), were found to be co instantaneous significance compared with their parental cells. The expression of the five proteins was validated by quantitative PCR and western blot, and the western blot results showed complete consistency with proteomic techniques. The five proteins are hopeful to become candidates for platinum resistance. These may be useful for further study of resistance mechanisms and screening of resistant biomarkers. PMID- 17269734 TI - Improvement of recovery and repeatability in liquid chromatography-mass spectrometry analysis of peptides. AB - Poor repeatability of peak areas is a problem frequently encountered in peptide analysis with nanoLiquid Chromatography coupled on-line with Mass Spectrometry (nanoLC-MS). As a result, quantitative analysis will be seriously hampered unless the observed variability can be corrected in some way. Currently, labeling techniques or addition of internal standards are often applied for this purpose. However, these procedures are elaborate and error-prone and may render complex samples even more complex. Moreover, whenever poor repeatability results from variable recovery, not just quantification, but also sensitivity is affected. We have studied the parameters influencing the repeatability of chromatographic peak areas for a model set of proteolytic peptides (i.e., a cytochrome c tryptic digest) in nanoLC-MS analysis. It is demonstrated that repeatability issues are mainly due to poor recovery of peptides from the sample vial. Problems are largely resolved by addition of an organic modifier to the sample vial to improve solubility of the peptides, but care needs to be taken not to lose peptides due to reduced affinity for reversed-phase materials. Good results are obtained when applying dimethylsulfoxide (DMSO) for this purpose. When applying DMSO, repeatability increases, and the limit of detection (LOD) decreases. For the most hydrophobic peptides, a gain in LOD of at least an order of magnitude is obtained. In an aqueous sample containing 0.1% formic acid (FA), it is possible to detect 100-200 fmol of peptide, whereas +/-10 fmol can be detected in a sample containing 5% FA and 25% DMSO (10 microL injections). PMID- 17269732 TI - Quantitative proteomic and microarray analysis of the archaeon Methanosarcina acetivorans grown with acetate versus methanol. AB - Methanosarcina acetivorans strain C2A is an acetate- and methanol-utilizing methane-producing organism for which the genome, the largest yet sequenced among the Archaea, reveals extensive physiological diversity. LC linear ion trap-FTICR mass spectrometry was employed to analyze acetate- vs methanol-grown cells metabolically labeled with 14N vs 15N, respectively, to obtain quantitative protein abundance ratios. DNA microarray analyses of acetate- vs methanol-grown cells was also performed to determine gene expression ratios. The combined approaches were highly complementary, extending the physiological understanding of growth and methanogenesis. Of the 1081 proteins detected, 255 were > or =3 fold differentially abundant. DNA microarray analysis revealed 410 genes that were > or =2.5-fold differentially expressed of 1972 genes with detected expression. The ratios of differentially abundant proteins were in good agreement with expression ratios of the encoding genes. Taken together, the results suggest several novel roles for electron transport components specific to acetate-grown cells, including two flavodoxins each specific for growth on acetate or methanol. Protein abundance ratios indicated that duplicate CO dehydrogenase/acetyl-CoA complexes function in the conversion of acetate to methane. Surprisingly, the protein abundance and gene expression ratios indicated a general stress response in acetate- vs methanol-grown cells that included enzymes specific for polyphosphate accumulation and oxidative stress. The microarray analysis identified transcripts of several genes encoding regulatory proteins with identity to the PhoU, MarR, GlnK, and TetR families commonly found in the Bacteria domain. An analysis of neighboring genes suggested roles in controlling phosphate metabolism (PhoU), ammonia assimilation (GlnK), and molybdopterin cofactor biosynthesis (TetR). Finally, the proteomic and microarray results suggested roles for two-component regulatory systems specific for each growth substrate. PMID- 17269735 TI - A synthetic protein approach toward accurate mass spectrometric quantification of component stoichiometry of multiprotein complexes. AB - Quantitative description of protein interactions is crucial to understand and model molecular systems regulating various cellular activities. Here, we developed a novel peptide-concatenated standard (PCS) strategy for accurate mass spectrometric quantification of component stoichiometry of multiprotein complexes. In this strategy, tryptic peptides suitable for quantification are selected with their natural flanking sequences from each component of multiprotein complex and concatenated into a single synthetic protein called PCS. The concatenation guarantees equimolarity among the peptides added to the sample to obviate the need for preparation of accurately known amounts of individual peptides. The flanking sequences would equalize the excision efficiency of each peptide between the PCS and the target protein to improve the accuracy of quantification. To validate this strategy, we quantified the budding yeast eIF2Bgamma, the gamma subunit of eukaryotic initiation factor 2B, using a PCS composed of tryptic peptides from eIF2Bgamma with their flanking sequences. An identical sample-to-standard signal ratio was obtained within 5% measured error for these peptides, including the one prone to incomplete digestion, thereby proving the principle of PCS strategy. We applied the strategy to reveal the stoichiometry of the eIF2B-eIF2 complex using a PCS covering the 5 eIF2B and 3 eIF2 components. While the complex contained equimolar amounts of the eIF2B subunits, the ratio of each eIF2 subunit to eIF2B was 30-40%. The PCS strategy would provide a versatile method to quantitatively analyze compositional alteration of multiprotein complexes or dynamics of protein-protein interactions in response to various stimuli. PMID- 17269736 TI - Comprehensive peptidome analysis of mouse livers by size exclusion chromatography prefractionation and nanoLC-MS/MS identification. AB - Peptidome analysis has received increasing attention in recent years. Cancer diagnosis by serum peptidome has also been reported by peptides' profiling for discovery of peptide biomarkers. Tissue, which may have a higher biomarker concentration than blood, has not been investigated extensively by means of peptidome analysis. Here, a method for the peptidome analysis of mouse liver was developed by the combination of size exclusion chromatography (SEC) prefractionation with nano-liquid chromatography-tamdem mass spectrometry (nanoLC MS/MS) analysis. The extracted peptides from mouse liver were separated according to their molecular weight using a size exclusion column. MALDI-TOF MS was used to characterize the molecular weight distribution of the peptides in fractions eluted from the SEC column. The low molecular weight (LMW) (MW < 3000 Da) peptides in the collected fractions were directly analyzed by LC-MS/MS which resulted in the identification of 1181 unique peptides (from 371 proteins). The high molecular weight (HMW) (MW > 3000 Da) peptides in the early two fractions from the SEC column were first digested with trypsin, and the resulted digests were then analyzed by LC-MS/MS, which led to the identification of 123 and 127 progenitor proteins of the HMW peptides in fractions 1 and 2, respectively. Analysis of the peptides' cleavage sites showed that the peptides are cleaved in regulation, which may reflect the protease activity and distribution in body, and also represent the biological state of the tissue and provide a fresh source for biomarker discovery. PMID- 17269737 TI - Proteome analysis of chloroplast mRNA processing and degradation. AB - Chloroplasts have a complex enzymatic machinery to adjust the relative half-life of their mRNAs to environmental signals. Soluble protein extracts from spinach (Spinacia oleracea L.) chloroplasts that correctly reproduce in vitro the differential mRNA stability observed in vivo were analyzed using shotgun proteomics to identify the proteins that are potentially involved in this process. The combination of a novel strategy for the database-independent detection of proteins from MS/MS data with standard database searches allowed us to identify 243 proteins with high confidence, which include several nucleases and RNA binding proteins but also proteins that have no reported function in chloroplast mRNA metabolism. Characterization of enzyme activities that adjust mRNA stability in response to illumination revealed that the dark-induced RNA degradation pathway involves enzymatic activities that differ from those that direct RNA processing and stabilization in the light. Dark-induced mRNA degradation comprises a MgCl2-independent and a MgCl2-dependent step, which releases nucleoside di- and monophosphates from the petD 3'-UTR precursor substrate. RNA degradation can be blocked with RNasin, a potent inhibitor of eukaryotic ribonucleases, suggesting that chloroplast mRNA degradation involves enzymes that are distinct from those found in prokaryotic-type RNA degradation. On the basis of the identified proteins and the in vitro characterization of the RNA degradation activities, we discuss scenarios and components that potentially determine plastid mRNA stability. PMID- 17269738 TI - Technical, experimental, and biological variations in isobaric tags for relative and absolute quantitation (iTRAQ). AB - We assess the reliability of isobaric-tags for relative and absolute quantitation (iTRAQ), based on different types of replicate analyses taking into account technical, experimental, and biological variations. In total, 10 iTRAQ experiments were analyzed across three domains of life involving Saccharomyces cerevisiae KAY446, Sulfolobus solfataricus P2, and Synechocystis sp. PCC 6803. The coverage of protein expression of iTRAQ analysis increases as the variation tolerance increases. In brief, a cutoff point at +/-50% variation (+/-0.50) would yield 88% coverage in quantification based on an analysis of biological replicates. Technical replicate analysis produces a higher coverage level of 95% at a lower cutoff point of +/-30% variation. Experimental or iTRAQ variations exhibit similar behavior as biological variations, which suggest that most of the measurable deviations come from biological variations. These findings underline the importance of replicate analysis as a validation tool and benchmarking technique in protein expression analysis. PMID- 17269740 TI - Dual-source mass spectrometer with MALDI-LIT-ESI configuration. AB - A novel linear ion trap (LIT) mass spectrometer with dual matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) ionization sources has been built in the MALDI-LIT-ESI configuration. The design features two independent ion source/ion optical channels connected to opposite ends of a single mass analyzer. The instrument consists of a commercial MALDI-LIT instrument modified by the addition of a home-built vacuum manifold, ion optical system, control electronics, and programming necessary to couple an atmospheric pressure interface to the commercial instrument. In addition to the added ESI functionality, the capabilities of the system also include simultaneous dual channel ion introduction and analysis and high-duty cycle electronic switching (<1 s) between ion channels. Analytical and ion chemical applications of the dual source system are explored. One analytical application is the enhanced protein sequence coverage achieved when using both ESI and MALDI to examine a tryptic digest of a six-protein mixture. The differences in the efficiency with which peptides in a mixture are ionized by the two methods give improved sequence coverage when both are applied. Other analytical applications include the use of the ions from one source as intensity or mass standards for the analyte ions from the other. An ion chemistry application involves the use of energy-resolved tandem mass spectrometry (MS/MS) to seek evidence for the generation of isomeric ions from a particular compound using the two ionization methods. A high level of agreement was achieved between the MS/MS spectra recorded under a variety of conditions after ESI and MALDI ionization; this provides evidence of the reproducibility and internal consistency of data from the dual source instrument. However, each of the peptides examined generated identical populations of structures in the two ionization methods under our conditions which are interpreted as involving slow cooling into the most stable minimum on the potential energy surface. PMID- 17269739 TI - Head-to-head comparison of serum fractionation techniques. AB - Multiple approaches for simplifying the serum proteome have been described. These techniques are generally developed across different laboratories, samples, mass spectrometry platforms, and analysis tools. Hence, comparing the available schemes is impossible from the existing literature because of confounding variables. We describe a head-to-head comparison of several serum fractionation schemes, including N-linked glycopeptide enrichment, cysteinyl-peptide enrichment, magnetic bead separation (C3, C8, and WCX), size fractionation, protein A/G depletion, and immunoaffinity column depletion of abundant serum proteins. Each technique was compared to results obtained from unfractionated human serum. The results show immunoaffinity subtraction is the most effective means for simplifying the serum proteome while maintaining reasonable sample throughput. The reported dataset is publicly available and provides a standard against which emergent technologies can be compared and evaluated for their contribution to serum-based biomarker discovery. PMID- 17269741 TI - Protein family classification with partial least squares. AB - The quality of protein function predictions relies on appropriate training of protein classification methods. Performance of these methods can be affected when only a limited number of protein samples are available, which is often the case in divergent protein families. Whereas profile hidden Markov models and PSI-BLAST presented significant performance decrease in such cases, alignment-free partial least-squares classifiers performed consistently better even when used to identify short fragmented sequences. PMID- 17269742 TI - Overexpression of biglycan in the heart of transgenic mice: an antibody microarray study. AB - Biglycan, a small leucine rich proteoglycan, is expressed in almost every tissue of the body, mainly in the extracellular matrix of connective tissues. Although there is an increasing amount of data on the biological role of biglycan protein, its function is still poorly understood. We aimed to gather more information about the biological function of biglycan protein in the cardiac tissues, and its role in signal transduction. Therefore, we generated transgenic mice overexpressing the human biglycan protein and analyzed the cardiac protein profile of transgenic offsprings using quantitative real-time (QRT)-PCR and proteomics. QRT-PCR results showed that most members of extracellular matrix were downregulated whereas cadherins, TGF-beta1, and TGF-beta2 were upregulated. Antibody microarrayer experiment revealed that pyk2, RAF-1, Mcl-1, syntrophin, calmodulin, isoforms of NOS protein family (eNOS, nNOS, and iNOS), and synaptotagmin proteins were unambiguously upregulated in the heart of biglycan transgenic mice. In this study we show that biglycan directly or indirectly activates proteins involved in cardiac remodeling (TGF-beta, pyk2), signal transduction (RAF-1, Mcl-1, syntrophin, calmodulin, nNOS p38MAPK and MAP kinases), cardioprotection (NOS family, TGF-beta) and Ca++ signaling (connexin, calmodulin, synaptotagmin). On the basis of the results presented here, we conclude that biglycan is a multifunctional extracellular protein that has a pivotal role in pathological remodeling of cardiac tissue and mediates cardioprotection. PMID- 17269743 TI - Latent periodicity of protein families, identified with the indel-aware algorithm. AB - Latent amino acid repeats seem to be widespread in genetic sequences and to reflect their structure, function, and evolution. We have recently identified latent periodicity in more than 150 protein families including protein kinases and various nucleotide-binding proteins. The latent repeats in these families were correlated to their structure and evolution. However, a majority of known protein families were not identified with our latent periodicity search algorithm. The main presumable reason for this was the inability of our techniques to identify periodicities interspersed with insertions and deletions. We designed the new latent periodicity search algorithm, which is capable of taking into account insertions and deletions. As a result, we identified many novel cases of latent periodicity peculiar to protein families. Possible origins of the periodic structure of these families are discussed. Summarizing, we presume that latent periodicity is present in a substantial portion of known protein families. The latent periodicity matrices and the results of Swiss-Prot scans are available from http://bioinf.narod.ru/del/. PMID- 17269744 TI - Proteomic investigation of glioblastoma cell lines treated with wild-type p53 and cytotoxic chemotherapy demonstrates an association between galectin-1 and p53 expression. AB - Global protein analysis of treated and untreated glioblastoma cell lines was performed. Proteomic analysis revealed the identity of proteins that were significantly modulated by the treatment with wild-type TP53 and the cytotoxic chemotherapy SN38. In particular, galectin-1 was found to be negatively regulated by transfection with TP53 and further down-regulated by SN38. Expression level changes were confirmed by Western blot. Subsequent analysis of several high-grade glioma cell lines demonstrated very high levels of galectin-1, regardless if the cell lines contained mutant or wild-type TP53. High expression of galectin-1 in a human orthotopic murine tumor model was also detected by immunohistochemistry and revealed a consistent pattern of preferential expression in peripheral or leading tumor edges. Further examination of galectin-1 expression through microarray analysis in tumor materials from patients confirmed galectin-1 as a valuable biomarker and possible therapeutic target. These results demonstrate the utility of using proteomic approaches to interrogate and identify potential useful targets for cancer therapy by evaluating specific tumor responses, either positive or negative, to various therapies. PMID- 17269745 TI - Circulating human monocytes in the acute coronary syndrome express a characteristic proteomic profile. AB - We examined the proteome of circulating monocytes of patients with acute coronary syndrome at different times in comparison to that of patients with stable coronary artery disease. On admission, the expression of 18 spot proteins was altered, 10 of which were totally absent. This pattern changed progressively, and at 6 months, there were no differences with the monocyte proteome of stable patients. PMID- 17269746 TI - Rapid enrichment of phosphopeptides from tryptic digests of proteins using iron oxide nanocomposites of magnetic particles coated with zirconia as the concentrating probes. AB - Iron oxide nanocomposites of magnetic particles coated with zirconia were used as affinity probes to selectively concentrate phosphopeptides from tryptic digests of alpha- and beta-caseins, milk, and egg white to exemplify the enrichment of phosphopeptides from complex samples. Phosphopeptides, in quantities sufficient for characterization by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS), were enriched by the affinity probes within only 30 s. The affinity probe-target species conjugates were separated from the sample solution simply by applying an external magnetic field. The detection limit for tryptic digest of beta-casein using this approach is approximately 45 fmol. Furthermore, we combined this enrichment method with a rapid enzymatic digestion method, that is, microwave-assisted enzymatic digestion using magnetic particles as the microwave absorbers, to speed up the tryptic digest reactions. Thus, we alternatively enriched phosphoproteins on the zirconia-coated particles followed by mixing with trypsin and heated the mixture in a microwave oven for 1 min. The particles remaining in the mixture were used as affinity probes to selectively enrich phosphopeptides from the tryptic digestion product by pipetting, followed by characterization using MALDI MS. Using the bifunctional zirconia-coated magnetic particles as both the affinity probes and the microwave absorbers could greatly reduce the time for the purification and characterization of phosphopeptides from complex samples. PMID- 17269747 TI - Automating MALDI sample plate loading. AB - We describe the design and implementation of a generic robotic solution to automate the loading of MALDI sample plates into a mass spectrometer. The soft- and hardware aspects are described together with the various safety issues that need to be addressed. The automation increases throughput by a factor of between 5- and 80-fold. PMID- 17269748 TI - The phosphorus source phytate changes the composition of the cell wall proteome in Bacillus subtilis. AB - Phytate is the most abundant phosphorus source in plants. Since Bacillus subtilis is a soil-dwelling bacterium, the focus of this study was to investigate whether it can use phytate as a phosphorus source. The extracellular proteome analysis revealed that phytate is an alternative phosphorus source to overcome the phosphate starvation response in B. subtilis. However, the phytase was not induced neither under phosphate starvation conditions nor by phytate addition. Surprisingly, the proteome analyses demonstrated a re-distribution of the major cell wall protease WprA from the cell wall to the extracellular medium in phytate supplemented medium. In contrast, several cell wall proteins such as autolysins and autolysin modifier proteins (e.g., LytB, -C, -D, -E, -F) are increased in the cell wall proteome in response to phytate which is not accompanied by increased transcription of the corresponding genes. These effects of phytate on the composition of the B. subtilis cell wall proteome do not depend on the acidic conditions, the increased sodium ion concentration, and the increased cell lysis. In addition, the previously predicted as cytoplasmic protein oxalate decarboxylase OxdC was identified as the most abundant cell wall protein which was induced at the transcriptional level due to the acidic conditions caused by phytate. PMID- 17269749 TI - A model for the recognition of protein kinases based on the entropy of 3D van der Waals interactions. AB - The study and prediction of kinase function (kinomics) is of major importance for proteome research due to the widespread distribution of kinases. However, the prediction of protein function based on the similarity between a functionally annotated 3D template and a query structure may fail, for instance, if a similar protein structure cannot be identified. Alternatively, function can be assigned using 3D-structural empirical parameters. In previous studies, we introduced parameters based on electrostatic entropy (Proteins 2004, 56, 715) and molecular vibration entropy (Bioinformatics 2003, 19, 2079) but ignored other important factors such as van der Waals (vdw) interactions. In the work described here, we define 3D-vdw entropies (degrees theta(k)) and use them for the first time to derive a classifier for protein kinases. The model classifies correctly 88.0% of proteins in training and more than 85.0% of proteins in validation studies. Principal components analysis of heterogeneous proteins demonstrated that degrees theta(k) codify information that is different to that described by other bulk or folding parameters. In additional validation experiments, the model recognized 129 out of 142 kinases (90.8%) and 592 out of 677 non-kinases (87.4%) not used above. This study provides a basis for further consideration of degrees theta(k) as parameters for the empirical search for structure-function relationships. PMID- 17269750 TI - Sonoreactor-based technology for fast high-throughput proteolytic digestion of proteins. AB - Fast (120 s) and high-throughput (more than six samples at once) in-gel trypsin digestion of proteins using sonoreactor technology has been achieved. Successful protein identification was done by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, MALDI-TOF-MS. Specific identification of the adenylylsulphate reductase alfa subunit from a complex protein mixture from Desulfovibrio desulfuricans ATCC 27774 was done as a proof of the methodology. The new sample treatment is of easy implementation, saves time and money, and can be adapted to online procedures and robotic platforms. PMID- 17269751 TI - Differentiation of Aeromonas isolated from drinking water distribution systems using matrix-assisted laser desorption/ionization-mass spectrometry. AB - The genus Aeromonas is one of several medically significant genera that have gained prominence due to their evolving taxonomy and controversial role in human diseases. In this study, matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) was used to analyze the whole cells of both reference strains and unknown Aeromonas isolates obtained from water distribution systems. A library of over 45 unique m/z signatures was created from 40 strains that are representative of the 17 recognized species of Aeromonas, as well as 3 reference strains from genus Vibrio and 2 reference strains from Plesiomonas shigelloides. The library was used to help speciate 52 isolates of Aeromonas. The environmental isolates were broken up into 2 blind studies. Group 1 contained isolates that had a recognizable phenotypic profile and group 2 contained isolates that had an atypical phenotypic profile. MALDI-MS analysis of the water isolates in group 1 matched the phenotypic identification in all cases. In group 2, the MALDI-MS based determination confirmed the identity of 18 of the 27 isolates. These results demonstrate that MALDI-MS analysis can rapidly and accurately classify species of the genus Aeromonas, making it a powerful tool especially suited for environmental monitoring and detection of microbial hazards in drinking water. PMID- 17269752 TI - Peak parking-moment analysis. A strategy for the study of the mass-transfer kinetics in the stationary phase. AB - The combination of peak parking and moment analysis is proved to be a powerful strategy for studying the molecular diffusivity of solute molecules in stationary phases and for determining the corresponding kinetic parameters. The physical meaning of the traditional kinetic parameter, gammasDs, the diffusion coefficient of solute molecules in stationary phases, is first clarified. A second kinetic parameter, DLs, is then derived from gammasDs, and the correspondence between DLs and the surface diffusion coefficient, Dsur, is discussed. Then, the results of peak parking experiments carried out with RPLC systems using aqueous methanol solutions and C18-silica columns are reported. The moments of pulse responses were measured and are analyzed. The values and some characteristics of DLs measured by the peak parking-moment analysis method are compared with those of Dsur determined using the pulse response-moment analysis method. The comparison of the numerical values of DLs and Dsur suggests that DLs is nearly equal to Dsur and that it exhibits the same dependence on the retention strength as does Dsur with regard to the mass-transfer kinetics and extrathermodynamics. This comparison allows us to conclude that DLs corresponds to Dsur. The advantages and disadvantages of the peak parking-moment analysis method were compared with those of the pulse response-moment analysis method. The combination of these two methods provides a comprehensive strategy for measuring the mass-transfer kinetics in the stationary phase. PMID- 17269753 TI - Elucidation of control mechanisms discovered during adaptive manipulation of [Ru(dpb)3](PF6)2 emission in the solution phase. AB - To design methodologies that will allow researchers to directly correlate the results of adaptive control experiments with physiochemical control pathways in arbitrary complex molecular systems it is imperative that prototype systems are developed and that exigent control pathways are understood. We have been interested in the results of adaptive control experiments in our laboratory involving the maximization of a ratio of two experimental observables: (1) the thermalized emission from the solution-phase coordination complex [Ru(dpb)3](PF6)2 and (2) the second harmonic signal (a purely intensity-dependent phenomenon) of the shaped laser fields. Using a rational pulse shaping strategy, we have made a measurement of the ratio spectrum (in essence the two-photon absorption cross section) for the molecule [Ru(dpb)3](PF6)2 in a room temperature solution of acetonitrile. This spectrum is highly varied across the accessible two-photon power spectrum of our broad-band laser pulses and demonstrates the existence of a control pathway wherein a shaped laser field can manipulate excited-state population (with respect to SHG) by conforming to the second-order spectral response of the molecule in solution. We show that our adaptive control algorithm is capable of taking advantage of these control pathways using simulated adaptive control experiments. Finally, we measure second-harmonic spectra of shaped laser fields discovered during an adaptive control experiment and show that these agree with simulation. These results suggest that our adaptive control experiment can be understood in the context of the elucidated spectral control pathway. PMID- 17269754 TI - A comparative investigation of Co2+ and Mn2+ incorporation into aluminophosphates by in situ XAS and DFT computation. AB - The incorporation processes of Mn2+ and Co2+ into the framework of aluminophosphate molecular sieve AlPO4-5, at the onset of crystallization, were investigated by in situ synchrotron X-ray absorption spectroscopy (XAS) and density functional theory (DFT) computation. The results indicated that the syntheses of MnAPO-5 and CoAPO-5 were different in the incorporation mechanism of metal ions. For the synthesis of CoAPO-5, Co2+ transferred from an octahedral into tetrahedral structure with crystal formation, while, for MnAPO-5, the Mn2+ transition to the tetrahedral structure was much more difficult and it occurred after the appearance of long-range ordered microporous structure. The DFT computations of model intermediates involved in the synthesis process suggested that much higher transformation energy of [Mn(OP(OH)3)4]2+ than that of [Co(OP(OH)3)4]2+ was responsible for the diversity of the incorporation behaviors. PMID- 17269755 TI - Time-resolved resonance Raman study of the reaction of the 2-fluorenylnitrenium ion with 2-fluorenylazide. AB - A time-resolved resonance Raman investigation of the reaction of the 2 fluorenylnitrenium ion with 2-fluorenylazide in a mixed aqueous solvent is presented. The reaction of the 2-fluorenylnitrenium ion with 2-fluorenylazide in the mixed aqueous solution generates two new species on the microsecond time scale. One of these species is identified as 2,2'-azobisfluorene, and the other species is tentatively assigned to a 1,4-bis-(2,2'-fluorenyl)-tetrazadiene cation intermediate. The structure and properties of these two species are briefly discussed. The reaction of the 2-fluorenylnitrenium ion with 2-fluorenylazide is also briefly compared to that of the 2-fluorenylnitrenium ion reactions with guanosine and water. PMID- 17269756 TI - Density functional studies on the thermal aryl migration in beta-dicarbonyl ylides and related compounds. AB - The potential energy surfaces for the unimolecular rearrangement reactions of beta-dicarbonyl ylides and beta-carbonylimidoyl ylides have been studied using the density functional method. All of the stationary points were determined at the B3LYP/LANL2DZdp level of theory. Four kinds of beta-dicarbonyl ylide species containing fluorine, chlorine, bromine, and iodine have been chosen in this work as model reactants. Also, five beta-carbonylimidoyl ylide molecules bearing nitrogen, phosphorus, arsenic, stibium, and bismuth have been used in the present study. In the latter reactions, two different reaction pathways have been proposed: (1) a 1,2-aryl shift to the pnicogen element and (2) A 1,2-aryl shift to the oxygen atom. That is, path 1 is reactant-->TS-1-->Pro-1 and path 2 is reactant-->TS-2-->Pro-2. Our theoretical findings strongly suggest that all intramolecular aryl migration reactions proceed via a one-step (concerted) reaction path. For the beta-dicarbonyl ylide species, the smaller the atomic number of the halogen atom, the lower the barrier height, the larger the reaction enthalpy, and, in turn, the easier it is to undergo the intramolecular aryl migration under thermal conditions. Alternatively, the heavier the pnicogen element in the beta-carbonylimidoyl ylides, the smaller the barrier height, and the larger the migration reaction enthalpy, even under thermal conditions. The results obtained allow a number of predictions to be made. PMID- 17269757 TI - Translational diffusion constants of the amino acids: measurement by NMR and their use in modeling the transport of peptides. AB - In this work, the translational self-diffusion constants, DT's, of 12 amino acids (Ala, Arg, Asn, Asp, Cys, Glu, His, Ile, Lys, Met, Phe, and Ser) are measured by field gradient NMR and extrapolated to infinite dilution. The experiments were carried out in D2O at 298 K at pD approximately =3.5 in 50 mM sodium phosphate buffer. Of these 12 amino acids, 6 are being reported for the first time (Asp, Cys, Glu, His, Lys, and Met) and the remaining 6 (Ala, Arg, Asn, Ile, Phe, and Ser) are compared with DT's from the literature. When corrected for differences in solvent viscosity and temperature, the discrepancy between DT's measured in the present work and those reported previously is always <8%, which is reasonable given the range of values reported previously by different groups. With the present work, DT's for all of the amino acids are now available. These diffusion constants are then used in modeling studies of the diffusion and free solution electrophoretic mobility, mu, of several model peptides. For this set of peptides, it is shown that modeling using revised input parameters results in improved agreement between model and experimental mobilities. PMID- 17269758 TI - Highly efficient ligands for dihydrofolate reductase from Cryptosporidium hominis and Toxoplasma gondii inspired by structural analysis. AB - The search for effective therapeutics for cryptosporidiosis and toxoplasmosis has led to the discovery of novel inhibitors of dihydrofolate reductase (DHFR) that possess high ligand efficiency: compounds with high potency and low molecular weight. Detailed analysis of the crystal structure of dihydrofolate reductase thymidylate synthase from Cryptosporidium hominis and a homology model of DHFR from Toxoplasma gondii inspired the synthesis of a new series of compounds with a propargyl-based linker between a substituted 2,4-diaminopyrimidine and a trimethoxyphenyl ring. An enantiomerically pure compound in this series exhibits IC50 values of 38 and 1 nM against C. hominis and T. gondii DHFR, respectively. Improvements of 368-fold or 5714-fold (C. hominis and T. gondii) relative to trimethoprim were generated by synthesizing just 14 new analogues and by adding only a total of 52 Da to the mass of the parent compound, creating an efficient ligand as an excellent candidate for further study. PMID- 17269759 TI - Optimization of novel acyl pyrrolidine inhibitors of hepatitis C virus RNA dependent RNA polymerase leading to a development candidate. AB - Optimization of a pyrrolidine-based template using structure-based design and physicochemical considerations has provided a development candidate 20b (3082) with submicromolar potency in the HCV replicon and good pharmacokinetic properties. PMID- 17269760 TI - Cobaloximes as functional models for hydrogenases. 2. Proton electroreduction catalyzed by difluoroborylbis(dimethylglyoximato)cobalt(II) complexes in organic media. AB - Cobaloximes are effective electrocatalysts for hydrogen evolution and thus functional models for hydrogenases. Among them, difluoroboryl-bridged complexes appear both to mediate proton electroreduction with low overpotentials and to be quite stable in acidic conditions. We report here a mechanistic study of [Co(dmgBF2)2L] (dmg2- = dimethylglyoximato dianion; L = CH3CN or N,N dimethylformamide) catalyzed proton electroreduction in organic solvents. Depending on the applied potential and the strength of the acid used, three different pathways for hydrogen production were identified and a unified mechanistic scheme involving cobalt(II) or cobalt(III) hydride species is proposed. As far as working potential and turnover frequency are concerned, [Co(dmgBF2)2(CH3CN)2], in the presence of p-cyanoanilinium cation in acetonitrile, is one of the best synthetic catalysts of the first-row transition metal series for hydrogen evolution. PMID- 17269761 TI - Photoinduced spin transition for Iron(II) compounds with liquid-crystal properties. AB - The iron(II) compounds [Fe(3Cn-L)2(NCS)2] (n = 6 (1), n = 8 (2), n = 10 (3), n = 12 (4), n = 14 (5), n = 16 (6), n = 18 (7), n = 20 (8), and n = 22 (9)) were synthesized and their physical properties characterized by polarizing optical microscopy, differential scanning calorimetry, and powder X-ray analysis, where 3Cn-L denotes bidentate Schiff-base ligands formed from the corresponding aniline derivatives and pyridine-2-carboxyaldehyde. The iron(II) compounds 4-8 exhibited crystal to liquid-crystal transitions at 318, 334, 345, 338, and 347 K, respectively. Variable-temperature magnetic susceptibility measurements revealed that the compounds 1-9 exhibit spin-crossover behavior between the high-spin and low-spin states and a photoinduced spin transition from a low-spin state to a metastable high-spin state. Therefore, the iron(II) compounds 4-8 can undergo spin-crossover and photoinduced spin transition as well as have liquid-crystal properties all in a single molecule. Compounds with multifunctions are important in the development of molecular switches and optical materials. PMID- 17269762 TI - Synthesis, structure, and redox properties of N-confused bis(porphyrinatonickel(II)) linked by o-xylene. AB - In a reaction of 5,10,15,20-tetraaryl-2-aza-21-carbaporphyrinato nickel(II) 2 with alpha,alpha'-dibromo-o-xylene, three different complexes containing a xylene moiety were obtained in the presence of a proton scavenger. The products were characterized by mass spectrometry, UV-vis, NMR, and, in the case of the dimeric complex 3, X-ray crystallographic analysis (space group P, a =16.455(3) A, b = 16.776(3) A, c = 18.400(4) A, alpha = 77.43(3) degrees , beta = 75.31(3) degrees , gamma = 66.20(3) degrees , V = 4457.1(19) A3, Z = 2). The monomeric species, diamagnetic 4 and paramagnetic 5, contain one and two bromoxylene residues, respectively, while in 3, the xylene bridge links two macrocyclic subunits, involving their internal carbons (C21) coordinated to diamagnetic nickel(II). Cyclovoltammetric measurements for o-xylene-linked bis(carbaporphyrinoid) 3 indicate cooperative effects resulting from an interaction between the subunits despite the isolation of their aromatic pi-bond systems. An EPR-controlled titration of 3 with bromine allows consecutive detection of the mono- and bis oxidized species (3Br, 3Br2). The spectral patterns and spin-Hamiltonian parameters indicate metal-centered oxidation in 3Br (gx = 2.358, gy = 2.150, gz = 2.062, A(Br)x = 15, A(Br)y = 35, A(Br)z = 129 G) and interaction of two electron spins of nickel(III) ions in 3Br2 (gx = 2.328, gy = 2.195, gz = 2.065, D = 0.0173 cm(-)1, E = -0.0018 cm(-1), A(Br)z = 63 G). A product of the chemical reduction of a protonated form of the dimer was also detected by means of EPR (g1 = 2.298, g2 = 2.218, g3 = 2.192), although no interaction between the nickel(I) centers can be observed for the reduced species. PMID- 17269763 TI - Chromium carbonyl nitrosyls: comparison with isoelectronic manganese carbonyl derivatives. AB - Density functional methods indicate that the global minimum for Cr2(NO)2(CO)8 is a staggered D4d structure in accord with experiment and analogous to the isoelectronic Mn2(CO)10. For the unsaturated Cr2(NO)2(CO)n derivatives the lowest energy structures are very different from the lowest energy structures for the isoelectronic Mn2(CO)n+2 derivatives. Thus the global minimum for Cr2(NO)2(CO)7 is an unbridged structure with a Cr(NO)(CO)4 fragment linked to a Cr(NO)(CO)3 fragment through a Cr=Cr double bond. For Cr2(NO)2(CO)6 the global minimum is a structure with two bridging CO groups, whereas the global minimum for Mn2(CO)8 is an unbridged structure. For Cr2(NO)2(CO)5 both NO groups are bridging NO groups with one of them having a short enough Cr-O distance to be considered a formal five-electron donor eta2-mu-NO group. Thus the isoelectronic substitution of NO for CO with a necessary adjustment in the central metal atom can lead to significant shifts in the relative energies of various structural types of metal carbonyl nitrosyls, particularly for unsaturated molecules. For the mononuclear Cr(NO)2(CO)3 the theoretical structure differs from that deduced from matrix isolation experiments. Moreover, the nu(CO) and nu(NO) vibrational frequencies predicted here for Cr(NO)2(CO)3 correspond more closely with the unassigned species labeled "Cr(NO)(CO)x" in the experiments rather than the species claimed to be Cr(NO)2(CO)3. PMID- 17269764 TI - Resolution of enantiomers in solution and determination of the chirality of extended metal atom chains. AB - The resolution of enantiomers of extended metal atom chains of the type Ni3[(C5H5N)2N]4Cl2 has been accomplished by chromatographic methods in solution, and the chirality was determined using vibrational circular dichroism, electronic circular dichroism, optical rotatory dispersion, and density functional theory calculations. PMID- 17269765 TI - Synthesis of a selenidostannate(IV), [Mn(tepa).Sn3Se7]n, demonstrating the transformation from achiral to chiral and dimeric to polymeric structure. AB - Although a number of chalcogenostannates have been obtained by using [M(amine)m]n+ as the structure director, these materials with chiral metal complex ions are usually achiral because they are a racemic mix of chiral complex cations. A chiral selenidostannate, [Mn(tepa).Sn3Se7]n (1; tepa = tetraethylenepentamine), containing incorporated [Mn(tepa)]2+ units, is reported herein. The unique structure is just like a grapevine appended with chiral grapes. In the same reaction, a centrosymmetric compound, [Mn(tepa)]2(mu2-Sn2Se6) (2), in which the Sn2Se64- anion acts as a bridge coordinating to [Mn(tepa)]2+ cations, has also been obtained. This is a reaction-time-related process in which compound 2 transformed gradually to 1 after prolonging the reaction time. This phenomenon demonstrates a transformation from achiral to chiral and dimeric to polymeric selenidostannate. PMID- 17269766 TI - Exploring the subtleties of drug-receptor interactions: the case of matrix metalloproteinases. AB - By solving high-resolution crystal structures of a large number (14 in this case) of adducts of matrix metalloproteinase 12 (MMP12) with strong, nanomolar, inhibitors all derived from a single ligand scaffold, it is shown that the energetics of the ligand-protein interactions can be accounted for directly from the structures to a level of detail that allows us to rationalize for the differential binding affinity between pairs of closely related ligands. In each case, variations in binding affinities can be traced back to slight improvements or worsening of specific interactions with the protein of one or more ligand atoms. Isothermal calorimetry measurements show that the binding of this class of MMP inhibitors is largely enthalpy driven, but a favorable entropic contribution is always present. The binding enthalpy of acetohydroxamic acid (AHA), the prototype zinc-binding group in MMP drug discovery, has been also accurately measured. In principle, this research permits the planning of either improved inhibitors, or inhibitors with improved selectivity for one or another MMP. The present analysis is applicable to any drug target for which structural information on adducts with a series of homologous ligands can be obtained, while structural information obtained from in silico docking is probably not accurate enough for this type of study. PMID- 17269769 TI - Collagen-related peptides: self-assembly of short, single strands into a functional biomaterial of micrometer scale. PMID- 17269767 TI - Sulfur K-edge X-ray absorption spectroscopy as a probe of ligand-metal bond covalency: metal vs ligand oxidation in copper and nickel dithiolene complexes. AB - A combination of Cu L-edge and S K-edge X-ray absorption data and density functional theory (DFT) calculations has been correlated with 33S electron paramagnetic resonance superhyperfine results to obtain the dipole integral (Is) for the S 1s-->3p transition for the dithiolene ligand maleonitriledithiolate (MNT) in (TBA)2[Cu(MNT)2] (TBA= tetra-n-butylammonium). The results have been combined with the Is of sulfide derived from XPS studies to experimentally obtain a relation between the S 1s-->4p transition energy (which reflects the charge on the S atom, QSmol) and the dipole integral over a large range of QSmol. The results show that, for high charges on S, Is can vary from the previously reported Is values, calculated using data over a limited range of QSmol. A combination of S K-edge and Cu K- and L-edge X-ray absorption data and DFT calculations has been used to investigate the one-electron oxidation of [Cu(MNT)2]2- and [Ni(MNT)2]2-. The conversion of [Cu(MNT)2]2- to [Cu(MNT)2]- results in a large change in the charge on the Cu atom in the molecule (QCumol) and is consistent with a metal-based oxidation. This is accompanied by extensive charge donation from the ligands to compensate the high charge on the Cu in [Cu(MNT)2]- based on the increased S K-edge and decreased Cu L-edge intensity, respectively. In contrast, the oxidation of [Ni(MNT)2]2- to [Ni(MNT)2]- results in a small change in QNimol, indicating a ligand-based oxidation consistent with oxidation of a molecular orbital, psiSOMO (singly occupied molecular orbital), with predominant ligand character. PMID- 17269768 TI - Interplay of structure and vibrational dynamics in six-coordinate heme nitrosyls. PMID- 17269770 TI - Reversible, erasable, and rewritable nanorecording on an H2 rotaxane thin film. PMID- 17269771 TI - Synthesis, structure, and magnetic properties of valence ambiguous dinuclear antiferromagnetically coupled cobalt and ferromagnetically coupled iron complexes containing the chloranilate(2-) and the significantly stronger coupling chloranilate(*3-) radical trianion. AB - Dinuclear [(TPyA)MII(CA2-)MII(TPyA)]2+ [TPyA=tris(2-pyridylmethyl)amine; CA2 =chloranilate dianion; M=Co (1(2+)), Fe (2(2+))] complexes have been prepared by the reaction of M(BF4)(2).6H2O, TPyA, H2CA, and triethylamine in MeOH solution. Their reduced forms [(TPyA)MII(CA*3-)MII(TPyA)]+ [M=Co(1+), Fe (2+)] have been synthesized by using cobaltocene, and oxidized forms of 1, [(TPyA)CoIII(CAn)CoIII(TPyA)]z+ [z=3, n=3- (1(3+)); z=4, n=2- (1(4+))], have been obtained by using FcBF4 and ThianBF4 (Fc=ferrocenium; Thian=thianthrinium), respectively. The dinuclear compound bridged chloranilates (CA2- or CA*3-) were isolated and characterized by X-ray crystallography, electrochemistry, magnetism, and EPR spectroscopy. Unlike the other redox products, valence ambiguous 13+ forms via a complex redox-induced valence electron rearrangement whereby the one electron oxidation of the [CoIICA2-CoII]2+ core forms [CoIIICA*3-CoIII]3+, not the expected simple 1-e- transfer mixed-valent [CoIICA2-CoIII]3+ core. The M ions in 1 and 2 have a distorted octahedral geometry by coordination with four nitrogens of a TPyA, two oxygens of a chloranilate. Due to the interdimer offset face-to-face pi-pi and/or herringbone interactions, all complexes show extended 1 D and/or 2-D supramolecular structures. The existence of CA*3- in 1(3+) is confirmed from both solid-state magnetic and solution EPR data. Co-based 1n+ exhibit antiferromagnetic interactions [1(2+): g=2.24, J/kB=-0.65 K (-0.45 cm-1); 1+: g=2.36, J/kB=-75 K (52 cm-1)], while Fe-based 2n+ exhibit ferromagnetic interactions [2(2+): g=2.08, J/kB=1.0 K (0.70 cm-1); 2+: g=2.03, J/kB=28 K (19 cm 1)] [H=-2JS1.S2 for 12+ and 2(2+); H=-2J(S1.S2+S2.S3) for 1+ and 2+]. Thus, due to direct spin exchange CA*3- is a much strong spin coupling linkage than the superexchange spin-coupling pathway provided by CA2-. PMID- 17269772 TI - Activation of oxygen by metallic gold in Au/TiO2 catalysts. PMID- 17269773 TI - Reversible switching of the sol-gel transition with ultrasound in rhodium(I) and iridium(I) coordination networks. AB - Reversible coordination networks were prepared by combining diphenylphosphinite telechelic polytetrahydrofuran (2) with [RhCl(COD)]2 or [IrCl(COD)]2 in chloroform. Both systems resulted in stable gels at concentrations above 50 and 30 g/L for the rhodium(I) and iridium(I) networks, respectively. The rheological properties of the two coordination networks (100 g/L) were determined with oscillatory shear experiments, which showed that the elastic moduli are constant over a wide frequency range, indicating gel-like behavior; the iridium(I) gel has an elastic modulus distinctly higher (2.8x10(3) Pa) than that of the rhodium(I) gel (1.0x10(3) Pa). Ultrasonication of the rhodium(I) gel caused liquefaction after 3 min; regelation occurred 1 min after sonication was stopped. The iridium(I) gel was also liquefied after 3 min of sonication, but regelation took 1.5 h at room temperature and more than 10 days at -20 degrees C. 31P NMR measurements on model complexes showed that the large differences in gelation times are in agreement with the ligand exchange kinetics of the rhodium(I) and iridium(I) complexes. We propose that sonication of the gels results in ligand exchange, which changes the network topology without changing the coordination chemistry. Upon sonication, the fraction of metal centers in active cross-links decreases and thereby reduces the gel fraction to zero. The system is not at equilibrium, and upon standing the gel fraction increases at a rate that is determined by the exchange kinetics of the metal complex. The observed effects offer opportunities to use ultrasound in the activation of dormant transition metal catalysts. PMID- 17269774 TI - Assignment of individual metal redox states in a metalloprotein by crystallographic refinement at multiple X-ray wavelengths. PMID- 17269775 TI - Sonochemical synthesis of nanosized hollow hematite. PMID- 17269776 TI - Probing hydrogen bonding and ion-carbonyl interactions by solid-state 17O NMR spectroscopy: G-ribbon and G-quartet. AB - We report solid-state 17O NMR determination of the 17O NMR tensors for the keto carbonyl oxygen (O6) of guanine in two 17O-enriched guanosine derivatives: [6 17O]guanosine (G1) and 2',3',5'-O-triacetyl-[6-17O]guanosine (G2). In G1.2H2O, guanosine molecules form hydrogen-bonded G-ribbons where the guanine bases are linked by O6...H-N2 and N7...H-N7 hydrogen bonds in a zigzag fashion. In addition, the keto carbonyl oxygen O6 is also weakly hydrogen-bonded to two water molecules of hydration. The experimental 17O NMR tensors determined for the two independent molecules in the asymmetric unit of G1.2H2O are: Molecule A, CQ=7.8+/ 0.1 MHz, etaQ=0.45+/-0.05, deltaiso=263+/-2, delta11=460+/-5, delta22=360+/-5, delta33=-30+/-5 ppm; Molecule B, CQ=7.7+/-0.1 MHz, etaQ=0.55+/-0.05, deltaiso=250+/-2, delta11=440+/-5, delta22=340+/-5, delta33=-30+/-5 ppm. In G1/K+ gel, guanosine molecules form extensively stacking G-quartets. In each G-quartet, four guanine bases are linked together by four pairs of O6...H-N1 and N7...H-N2 hydrogen bonds in a cyclic fashion. In addition, each O6 atom is simultaneously coordinated to two K+ ions. For G1/K+ gel, the experimental 17O NMR tensors are: CQ=7.2+/-0.1 MHz, etaQ=0.68+/-0.05, deltaiso=232+/-2, delta11=400+/-5, delta22=300+/-5, delta33=-20+/-5 ppm. In the presence of divalent cations such as Sr2+, Ba2+, and Pb2+, G2 molecules form discrete octamers containing two stacking G-quartets and a central metal ion, that is, (G2)4-M2+-(G2)4. In this case, each O6 atom of the G-quartet is coordinated to only one metal ion. For G2/M2+ octamers, the experimental 17O NMR parameters are: Sr2+, CQ=6.8+/-0.1 MHz, etaQ=1.00+/-0.05, deltaiso=232+/-2 ppm; Ba2+, CQ=7.0+/-0.1 MHz, etaQ=0.68+/-0.05, deltaiso=232+/-2 ppm; Pb2+, CQ=7.2+/-0.1 MHz, etaQ=1.00+/-0.05, deltaiso=232+/-2 ppm. We also perform extensive quantum chemical calculations for the 17O NMR tensors in both G-ribbons and G-quartets. Our results demonstrate that the 17O chemical shift tensor and quadrupole coupling tensor are very sensitive to the presence of hydrogen bonding and ion-carbonyl interactions. Furthermore, the effect from ion-carbonyl interactions is several times stronger than that from hydrogen-bonding interactions. Our results establish a basis for using solid state 17O NMR as a probe in the study of ion binding in G-quadruplex DNA and ion channel proteins. PMID- 17269777 TI - n-Butyllithium/N,N,N',N'-tetramethylethylenediamine-mediated ortholithiations of aryl oxazolines: substrate-dependent mechanisms. AB - n-Butyllithium/N,N,N',N'-tetramethylethylenediamine-mediated ortholithiations of aryloxazolines are described. Methyl substituents on the aryloxazoline and substituents at the meta position of the arenes (methoxy, oxazolinyl, and fluoro) influence the rates and the mechanisms. Monomer- and dimer-based reactions are implicated. Density functional calculations probe details of the mechanism and suggest the origins of cooperative effects in meta-substituted aryl oxazolines. PMID- 17269778 TI - Probing the reversibility of sidewall functionalization using carbon nanotube transistors. PMID- 17269780 TI - Asymmetric reductive coupling of dienes and aldehydes catalyzed by nickel complexes of spiro phosphoramidites: highly enantioselective synthesis of chiral bishomoallylic alcohols. PMID- 17269781 TI - Convenient synthesis of green diisoindolodithienylpyrromethene-dialkynyl borane dyes. AB - [structure: see text] Versatile dyes based on diisoindolodithienylpyrromethene substituted at the boron center by alkynylaryl chromophores have been developed that efficiently fluorescence in the near infrared. Fast intramolecular energy transfer from the appended alkynyl units to the central core provides Stokes shifts above 16,000 cm(-1). PMID- 17269782 TI - Unsymmetrical calix[4]arene bisporphyrin Pacman. AB - [structure: see text] The synthesis of a Pacman heterobisporphyrin associating an octaethyl porphyrinatozinc (ZnOEP) energy donor and a triaryl porphyrinatozinc (ZntPP) energy acceptor around a calix[4]arene spacer is described. Contrary to previous symmetrical architectures, correlations between the chromophores in the unsymmetrical calixarene bisporphyrin Pacman scaffold can now be observed in ROESY experiments. Independent of the excitation wavelength, only the luminescence of the ZntPP moiety was observed corresponding to quenching of the OEP moiety's emission. PMID- 17269784 TI - Competing supramolecular assembly of amphiphiles to form micelles or pseudorotaxanes. AB - [reaction: see text] Micelles of an amphiphile that encapsulate the added dye in water can be released, upon addition of alpha-CD, to form pseudorotaxane. The equilibrium between the micelles and the pseudorotaxanes and the absorption spectra of solution are controlled by temperature reversibly. PMID- 17269783 TI - Nickel-catalyzed synthesis of acrylamides from alpha-olefins and isocyanates. AB - [reaction: see text] The nickel(0)-catalyzed coupling of alpha-olefins and isocyanates proceeds in the presence of the N-heterocyclic carbene ligand IPr to provide alpha,beta-unsaturated amides. Carbon-carbon bond formation occurs preferentially at the 2-position of the olefin. The N-tert-butyl amide products can be converted to the corresponding primary amides under acidic conditions. PMID- 17269785 TI - Effect of ginsenosides on glucose uptake in human Caco-2 cells is mediated through altered Na+/glucose cotransporter 1 expression. AB - In this study, we measured the effect of ginsenosides on glucose uptake using the Caco-2 cell system. At submicromolar concentrations, these compounds exhibited marked effects on the rate of glucose transport across the differentiated Caco-2 cell monolayer. Compound K (CK), the main intestinal bacterial metabolite of the protopanaxadiol ginsenosides, significantly enhanced the steady-state glucose transport rate to about 50% of the control sample rate (from 1.54 +/- 0.09 to 2.25 +/- 0.15 nmol/min). Conversely, the protopanaxatriol ginsenoside Rg1 inhibited glucose transport to about 70% of the original rate (from 1.54 +/- 0.09 to 1.02 +/- 0.05 nmol/min). Consistent with the effect on glucose uptake rate, CK and Rg1 conferred a significant and paralleled alteration on both the protein and mRNA expression levels of the Na+/glucose cotransporter 1 (SGLT1) gene. Unlike SGLT1, there is no significant alteration on the protein or mRNA levels of GLUTs in CK- or Rg1-treated cells. Taken together, our results demonstrate that ginsenosides CK and Rg1 elicited potent enhancing and suppressing effects, respectively, on glucose uptake across human intestinal Caco-2 monolayer through modulation of SGLT1 expression. PMID- 17269786 TI - Synthesis and phytotoxicity of new ionic liquids incorporating chiral cations and/or chiral anions. AB - The aim of this work was to synthesize chiral ionic liquids as chiral solvents for organic synthesis and to evaluate the phyto(eco)toxicity of the new products and starting N-alkylimidazoles and their potential environmental influence on soil and plants. Chiral ionic liquids containing anions such as Cl-, Br-, TsO-, PF6(-), NO3(-), CF3SO3(-), and (+)- and (-)-C6H5CH(OH)C(O)O- were synthesized using (-)-(1R)-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-ethyl [(-)-(1R)-nopyl] halides (X = Cl, Br) and tosylate in 62-100% yields. The chloride 7 and the nitrate 13 ionic liquids possessed a toxicity dependent on the applied concentration. The lowest concentration causing a distinct reduction in plant germination/growth was 100 mg/kg. Spring barley better tolerated the ionic liquids (200 mg/kg) than common radish (100 mg/kg). The nitrate liquid did not exhibit an inhibiting effect on the germination ability of seeds. The starting N methylimidazole used in lower concentrations (1 and 10 mg/kg of soil dry weight) was not phytotoxic, in contrast to higher doses (>1000 mg/kg). PMID- 17269787 TI - Identification of new, odor-active thiocarbamates in cress extracts and structure activity studies on synthesized homologues. AB - New, odorant nitrogen- and sulfur-containing compounds are identified in cress extracts. Cress belongs to the botanical order Brassicales and produces glucosinolates, which are important precursors of nitrogen- and sulfur-containing compounds. Those compounds often present low perception thresholds and various olfactive notes and are thus of interest to the flavor and fragrance chemistry. When the study of organonitrogen and organosulfur compounds is undertaken, Brassicale extracts are one of the matrices of choice. Cress extracts were studied by analytical (GC-MS, GC-FPD) and chemical (fractionation) means to identify new interesting odorant compounds. Two compounds that have never been reported in cress extracts, containing both nitrogen and sulfur, were discovered: N-benzyl O-ethyl thiocarbamate and N-phenethyl O-ethyl thiocarbamate. These two molecules being of organoleptic interest, their homologues were synthesized and submitted to organoleptic tests (static and GC-sniffing). Their odors evolve from garlic and onion over green, mushroom- and cress-like to fresh, spearmint-like. This paper presents the origin, chemical synthesis, and organoleptic properties of a series of O-alkyl thiocarbamates. PMID- 17269788 TI - Structure determination and sensory analysis of bitter-tasting 4-vinylcatechol oligomers and their identification in roasted coffee by means of LC-MS/MS. AB - Aimed at elucidating intense bitter-tasting molecules in coffee, various bean ingredients were thermally treated in model experiments and evaluated for their potential to produce bitter compounds. As caffeic acid was found to generate intense bitterness reminiscent of the bitter taste of a strongly roasted espresso type coffee, the reaction products formed were screened for bitter compounds by means of taste dilution analysis, and the most bitter tastants were isolated and purified. LC-MS/MS as well as 1-D/2-D NMR experiments enabled the identification of 10 bitter compounds with rather low recognition threshold concentrations ranging between 23 and 178 micromol/L. These bitter compounds are the previously unreported 1,3-bis(3',4'-dihydroxyphenyl) butane, trans-1,3-bis(3',4' dihydroxyphenyl)-1-butene, and eight multiply hydroxylated phenylindanes, among which five derivatives are reported for the first time. In addition, the occurrence of each of these bitter compounds in a coffee brew was verified by means of LC-MS/MS (ESI-) operating in the multiple reaction monitoring (MRM) mode. The structures of these bitter compounds show strong evidence that they are generated by oligomerization of 4-vinylcatechol released from caffeic acid moieties upon roasting. PMID- 17269789 TI - Optimization of protein fusion partner length for maximizing in vitro translation of peptides. AB - Using protein fusion partners for in vitro translation may increase solubility, assist in purification, or allow detection of small proteins and peptides. Here we show that the molar yield of peptide in a batch reaction may be maximized by optimizing the length of the translated product, which is composed of the fusion partner plus the peptide. Using truncated versions of GFP as a series of fusion partners, the molar yield increased approximately 3-fold as the length of the translated product was reduced from 250 to 100 amino acids. When the translated product was shortened below roughly 100 amino acids, molar yield fell as a result of proteolysis. This trend was verified using two fusion partners with different amino acid sequences. Furthermore, protease inhibitors were used to confirm that proteases were responsible for limiting accumulation of peptides below the optimal length. PMID- 17269790 TI - Feasibility of pressurization to speed up enzymatic hydrolysis of biological materials for multielement determinations. AB - The feasibility of pressurized solvents (liquids at a high pressure and/or high temperature without the subcritical point being reached) has been newly investigated to accelerate enzymatic hydrolysis processes of mussel tissue for multielement determinations. The target elements (Al, As, Cd, Co, Cu, Fe, Hg, Li, Mn, Pb, Se, Sr, V, and Zn) were released from dried mussel tissue by action of two proteases (pepsin and pancreatin), and they have been evaluated by inductively coupled plasma optical emission spectrometry (ICP-OES). Variables inherent to the enzymatic activity (pH, ionic strength, temperature, and enzyme mass) and factors affecting pressurization (static time, pressure, and number of cycles) were simultaneously studied by applying a Plackett-Burman design (PBD) as the screening method. Results showed that pH, ionic strength, and temperature were the most statistically significant factors (confidence interval of 95%) under pressurized conditions for pepsin, while pH and ionic strength affected pancreatin activity. This means that metal extraction is mostly attributed to enzymatic activity. The static time (enzymatic hydrolysis time) was found statistically nonsignificant for most of the elements, meaning that the hydrolysis procedure can be finished within a 2-15 min range. For pepsin, optimized conditions (pH 1.0, temperature 40 degrees C, pressure 1500 psi, static time 2 min, and number of cycles 3) gave quantitative extractions for As, Cd, Co, Cu, Hg, Li, Mn, Pb, Se, Sr, V, and Zn. The pepsin mass was 0.05 g, and the solution was Milli-Q water at pH 1.0 (adjusted with hydrochloric acid). For pancreatin, quantitative recoveries were only reached for As, Cd, Cu, Li, Pb, and Sr at room temperature, at a pressure of 1500 psi, for a static time of 2 min and a number of cycles of 3. The extraction solution was a 0.3 M potassium dihydrogen phosphate/potassium hydrogen phosphate buffer at a pH of 7.5 working at room temperature. Around 0.5 g of diatomaceous earth was used as dispersing agent for hydrolyses with either enzyme. Analytical performances, such as limits of detection and quantification and repeatability of the overall procedure, have been established. Finally, accuracy of the methods was assessed by analyzing seafood certified reference materials (GBW-08571, DORM-2, DOLT-3, TORT-2), fatty tissues certified reference materials (BCR 185, NIST 1577b), and fibrous certified reference materials (BCR 62, GBW-08501). PMID- 17269791 TI - I-shaped microchannel array chip for parallel electrophoretic analyses. AB - We demonstrate electrophoresis in I-shaped microchannels with a new design and operation principle. Unlike the conventional T- or cross-shaped microchannels, the simple I-shaped design makes it straightforward to integrate parallel microchannels with electrodes onto a microchip. The operation of the I-shaped microchannels has been enabled by the autonomous solution filling technique, which exploits the high gas solubility in poly(dimethylsiloxane) (PDMS). We fabricated an I-shaped microchannel array (IMA) chip by integrating 12 independent microchannels and 2 electrodes onto a 3 cm x 2 cm area in a PDMS glass hybrid microchip. For autonomous regulation of stable sample plugs in all the microchannels, we discovered that O2 plasma treatment of the PDMS-made reservoirs is effective. On the IMA chip, size-dependent separation of double stranded (ds) DNA and sequence-specific separation of single-stranded DNA were achieved. Specifically, 10 fragments in a 100-1000-bp dsDNA ladder were separated using hydroxyethylcellulose as a sieving matrix within a separation length of 2 mm, and polymerase chain reaction products of the wild-type K-ras gene and its point mutant were separated using a probe DNA-poly(dimethylacrylamide) conjugate on the basis of affinity capillary electrophoresis. The IMA chip presented here opens up a new possibility of large-scale integration of microchannels for high throughput electrophoretic analyses. PMID- 17269792 TI - Microfluidic channel flow cell for simultaneous cryoelectrochemical electron spin resonance. AB - A novel microfluidic electrochemical channel flow cell has been constructed for in situ operation in a cylindrical TE011 resonant ESR cavity under variable temperature conditions. The cell has a U-tube configuration, consisting of an inlet and outlet channel which run parallel and contain evaporated gold film working, pseudo-reference, and counter electrodes. This geometry was employed to permit use in conjunction with variable temperature apparatus which does not allow a flow-through approach. The cell is characterized qualitatively and quantitatively using the one-electron reduction of p-bromonitrobenzene in acetonitrile at room temperature as a model system, and the ESR signal-flow rate response is validated by use of three-dimensional digital simulation of the concentration profile for a stable electrogenerated radical species under hydrodynamic conditions. The cell is then used to obtain ESR spectra for a number of radical species in acetonitrile at 233 K, including the radical anions of m- and p-iodonitrobenzene, o-bromonitrobenzene, and m-nitrobenzyl chloride, the latter three being unstable at room temperature. Spectra are also presented for the radical anion of 2-chloranthraquinone and the crystal violet radical, which display improved resolution at low temperatures. PMID- 17269793 TI - Integrated molecule-format bioluminescent probe for visualizing androgenicity of ligands based on the intramolecular association of androgen receptor with its recognition Peptide. AB - Ligand-induced conformational changes of nuclear hormone receptors (NRs) are an important start-up of various hormone signaling. However, little is known of the bioanalytical use of the hormone-induced conformational changes of NRs. Here, we describe a generally applicable bioluminescence assay with a genetically encoded bioluminescent indicator to determine androgenicity of ligands based on the intramolecular association of the ligand binding domain of androgen receptor (AR LBD) with the "FQNLF" motif in the N-terminal domain of AR (AR NTD). Firefly luciferase (FLuc) was dissected into N-terminal (1-415 AA) and C-terminal (416 550 AA) fragments. The AR LBD and FQNLF motif of AR NTD were sandwiched between the dissected fragments of FLuc to construct a single molecule-format bioluminescent probe. Androgens induce the association of AR LBD with the FQNLF motif in the NTD, and the subsequent complementation of N- and C-terminal fragments of FLuc partially restores the activities of FLuc. A 10-5 M solution of 5alpha-dihydroxytestosterone (DHT) induced a quick increase in the luminescence intensities from cervical carcinoma-derived HeLa cells carrying the genetic indicator, which reached a plateau in 9 min, whereas DHT withdrawal from the cells by a medium change decreased the luminescence with a slower time course, i.e., approximately 2 h until returning to the background luminescence. The present luminescent indicator was found to exhibit high agonist selectivity and reproducible recovery of the luminescence to a repeated androgen addition and withdrawal. This is the first contribution that cellular signaling steps can be imaged with bioluminescence using a single molecule-format bioluminescence probe (Simbi), in which all the components required for a signal sensing and visualization are integrated. Simbi is applicable to developing biotherapeutic agents effecting to the AR signaling, and for screening adverse chemicals that possibly influence the signal transduction of AR. PMID- 17269794 TI - Integrated portable polymerase chain reaction-capillary electrophoresis microsystem for rapid forensic short tandem repeat typing. AB - A portable forensic genetic analysis system consisting of a microfluidic device for amplification and separation of short tandem repeat (STR) fragments as well as an instrument for chip operation and four-color fluorescence detection has been developed. The microdevice performs polymerase chain reaction (PCR) in a 160 nL chamber and capillary electrophoresis (CE) in a 7-cm-long separation channel. The instrumental design integrates PCR thermal cycling, electrophoretic separation, pneumatic valve fluidic control, and four-color laser excited fluorescence detection. A quadruplex Y-chromosome STR typing system consisting of amelogenin and three Y STR loci (DYS390, DYS393, DYS439) was developed and used for validation studies. The multiplex amplification of these 4 loci with 35 PCR cycles followed by CE separation and 4-color fluorescence detection was completed in 1.5 h. All the amplicons can be detected with a limit of detection of 20 copies of male standard DNA in the reactor. Real-world forensic analyses of oral swab and human bone extracts from case evidence were also successfully performed. Mixture analysis demonstrated that a balanced profile can be obtained even at a male-to-female template ratio of 1:10. The successful development and operation of this portable PCR-CE system establishes the feasibility of rapid point-of analysis DNA typing of forensic casework, of mass disaster samples or of individuals at a security checkpoint. PMID- 17269795 TI - Membrane topology prediction by hydropathy profile alignment: membrane topology of the Na(+)-glutamate transporter GltS. AB - Structural classification of families of membrane proteins by bioinformatics techniques has become a critical aspect of membrane protein research. We have proposed hydropathy profile alignment to identify structural homology between families of membrane proteins. Here, we demonstrate experimentally that two families of secondary transporters, the ESS and 2HCT families, indeed share similar folds. Members of the two families show highly similar hydropathy profiles but cannot be shown to be homologous by sequence similarity. A structural model was predicted for the ESS family transporters based upon an existing model of the 2HCT family transporters. In the model, the transporters fold into two domains containing five transmembrane segments and a reentrant or pore-loop each. The two pore-loops enter the membrane embedded part of the proteins from opposite sides of the membrane. The model was verified by accessibility studies of cysteine residues in single-Cys mutants of the Na+ glutamate transporter GltS of Escherichia coli, a member of the ESS family. Cysteine residues positioned in predicted periplasmic loops were accessible from the periplasm by a bulky, membrane-impermeable thiol reagent, while cysteine residues in cytoplasmic loops were not. Furthermore, two cysteine residues in the predicted pore-loop entering the membrane from the cytoplasmic side were shown to be accessible for small, membrane-impermeable thiol reagents from the periplasm, as was demonstrated before for the Na+-citrate transporter CitS of Klebsiella pneumoniae, a member of the 2HCT family. The data strongly suggests that GltS of the ESS family and CitS of the 2HCT family share the same fold as was predicted by comparing the averaged hydropathy profiles of the two families. PMID- 17269796 TI - Scrambling of phospholipids activates red cell membrane cholesterol. AB - Cholesterol is predicted to associate more strongly with the outer than the inner leaflet of plasma membrane bilayers based on the relative in vitro affinities of their phospholipids. Complex formation with the high-affinity species (especially saturated sphingomyelins) is said to reduce the chemical activity (escape potential or fugacity) of the sterol. We therefore tested the hypothesis that scrambling the sidedness of plasma membrane phospholipids of intact cells will increase the chemical activity of outer surface cholesterol. Upon activating the plasma membrane scramblase in intact human red cells by introducing ionomycin to raise cytoplasmic Ca++, phosphatidylserine became exposed and, concomitantly, the chemical activity of exofacial cholesterol was increased. (This was gauged by its susceptibility to cholesterol oxidase and its rate of transfer to cyclodextrin.) Similar behavior was observed in human fibroblasts. Two other treatments known to activate cell surface cholesterol (namely, exposure to glutaraldehyde and to low ionic-strength buffer) also brought phosphatidylserine to the cell surface but by a Ca++-independent mechanism. Given that phospholipid scrambling is important in blood coagulation and apoptosis, the concomitant activation of cell surface cholesterol could contribute to these and other pathophysiological signaling processes. PMID- 17269797 TI - New insights into the oxidative electrochemistry of vitamin E. AB - A combination of electrochemical and spectroscopic experiments have proven that the alpha-, beta-, gamma-, and delta-forms (vitamers) of the tocopherols (vitamin E) undergo a series of chemically reversible proton- and electron-transfer steps in dry organic solvents, such as acetonitrile or dichloromethane, to form cationic compounds: the cation radical, the dication, and the phenoxonium cation. The cationic compounds are extremely unusual in their high persistence compared with what is presently known about the oxidative stability of other phenols, particularly the phenoxonium cation of alpha-tocopherol, which is stable for at least several hours in nonaqueous solvents and is formed quantitatively by oxidation of the starting material at an applied potential of approximately +0.5 V vs ferrocene0/+ or with 2 mol equiv of NO+. PMID- 17269798 TI - Synthesis and aggregation behavior of pluronic F87/poly(acrylic acid) block copolymer in the presence of doxorubicin. AB - Poly(acrylic acid) (PAA) was polymerized on both termini of Pluronic F87 copolymer using the atom transfer radical polymerization technique to produce a novel block copolymer, PAA-b-F87-b-PAA (F87PAA). The loading of a cationic anticancer drug, doxorubicin (DOX), to F87PAA at different pH values was investigated using isothermal titration calorimetry (ITC), laser light scattering techniques, and UV-vis spectroscopy. At pH of 4.3-7.1, the ITC profile exhibited a significant exothermic peak, which indicated that the drug loading is an enthalpically driven process. At a pH of 4.3, the enthalpy maximum was significantly reduced in the presence of 2 M urea, indicating the existence of hydrogen bonds between the DOX and F87PAA copolymer. At a pH of 7.1, the fraction of bound DOX was close to the stoichiometric proportion of 1:1 to the molar concentration of carboxyl groups in the copolymer, where the drug loading is governed by electrostatic and stacking interactions. The TEM image of the complex indicated the formation of large compound micelles induced by the binding of DOX to the PAA segments. PMID- 17269799 TI - Stable immobilization of an oligonucleotide probe on a gold substrate using tripodal thiol derivatives. AB - We proposed an interface molecule for immobilization of DNA probes on solid substrates of DNA chips. We have designed and synthesized tripodal thiol derivatives for stable immobilization of oligonucleotide probes on a gold surface. On the basis of the tetrahedral structure of tripod, the tripodal thiol derivatives were bonded upright to the gold substrate, which would control the orientation of oligonucleotide probes. When the gold substrate with oligonucleotide probes tethered using the thiol derivatives was exposed to deionized water at higher temperatures, the tripodal interface molecules were attached to the gold surface more stably than the single contact molecules. The DNA chip platform combined with the functional interface molecule is suitable for a reproducible, inexpensive, and high-throughput detection system for genetic analyses in clinical diagnostics. PMID- 17269800 TI - Dewetting of thin polystyrene films under confinement. AB - The dewetting behavior of thin polystyrene (PS) film has been investigated by placing an upper plate with a ca. 140 nm gap from the underlying substrate with the spin-coated thin polymer films. Three different kinds of dewetting behaviors of thin PS film have been observed after annealing according to the relative position of the PS film to the upper plate. Since the upper plate is smaller than the underlying substrate, a part of the polymer film is not covered by the plate. In this region (I), thin PS film dewetting occurs in a conventional manner, as previously reported. While in the region covered by the upper plate (III), the PS film exhibits unusual dewetted patterns. Meanwhile, in the area right under the edge of the plate (II) (i.e., the area between region I and region III), highly ordered arrays of PS droplets are formed. Formation mechanisms of different dewetted patterns are discussed in detail. This study may offer an effective way to improve the understanding of various dewetting behaviors and facilitate the ongoing exploration of utilizing dewetting as a patterning technique. PMID- 17269801 TI - Competitive surface adsorption of solvent molecules and compactness of agglomeration in calcium hydroxide nanoparticles. AB - Calcium hydroxide forms unstable reactive nanoparticles that are stabilized when they are dispersed in ethylene glycol or 2-propanol. The aggregation behavior of these particles was investigated by contrast-variation small-angle neutron scattering (SANS), combined with small-angle X-ray scattering (SAXS). Nanoparticles on the order of 100 nm were found to aggregate into mass-fractal superstructures in 2-propanol, while forming more compact agglomerated aggregates with surface fractal behavior in ethylene glycol. Commensurate specific surface areas evaluated at the Porod limit were more than an order of magnitude greater in 2-propanol (approximately 200 m2.g(-1)) than in ethylene glycol (approximately 7 m2.g(-1)). This profound microstructural evolution, observed in similar solvents, is shown to arise from competitive solvent adsorption. The composition of the first solvent layer on the particles is determined over the full range of mixed solvent compositions and is shown to follow a quantifiable thermodynamic equilibrium, determined via contrast-variation SANS, that favors ethylene glycol over 2-propanol in the surface layer by about 1.4 kJ.mol(-1) with respect to the bulk solvent composition. PMID- 17269802 TI - Contact line shape on ultrahydrophobic post surfaces. AB - In this work, we investigate the configuration of the contact line of a water drop lying on an ultrahydrophobic post surface using the numerical algorithm Surface Evolver. For the special situation of Cassie wetting, we propose a modified definition of the contact line as the line in space where the meniscus starts to curve upward out of the plane of the composite surface. In our simulations, it is found that the contact line is very strongly distorted, indicating a strong tendency of the drop to "ball up" in those areas where it is not in contact with the solid surface. The distortion of the contact line corresponds to a pronounced deformation of the liquid-air interface around the base of the drop. We discuss the consequences of this distortion for the definition and practical measurement of the contact angle on ultrahydrophobic surfaces. PMID- 17269803 TI - Plate, wire, mesh, microsphere, and microtube composed of sodium titanate nanotubes on a titanium metal template. AB - Sodium titanate nanotube/titanium metal composites were synthesized by hydrothermal treatment of titanium metals with various morphologies such as plate, wire, mesh, microsphere, and microtube at 160 degrees C in aqueous NaOH solution and by the subsequent fixation treatment by calcination at 300 degrees C. The surface of the composite was covered with sodium titanate nanotubes with a diameter of approximately 7 nm, and the core part of the composite was titanium metal phase. The raw titanium metal acts as a template or a morphology-directing agent of micrometer size or more to arrange the nanotubes as well as a titanium source for the formation of nanotubes. The concentration of titanium species increases in the reaction solution as the dissolution of titanium metal is accelerated by the reaction between titanium and OH-. Furthermore, with an increase in concentration of titanium species in the reaction solution, the titanium species are re-precipitated as sodium titanate nanotubes onto the titanium metal. Titanium metal with a large surface area and volume can form sodium titanate nanotubes on the surface of the titanium metal, though titanium metal with a small volume and surface area tends to dissolve with the hydrothermal treatment. Even in the synthesis using titanium metal with a small volume and surface area, sodium titanate nanotubes are formed and cover the surface of the titanium metal by adding another titanium metal as a source of titanium species in the reaction solution. PMID- 17269804 TI - Dynamic force spectroscopy of the specific interaction between the PDZ domain and its recognition peptides. AB - To characterize the molecular basis of specific interactions of PDZ proteins, dynamic force spectroscopy (DFS) for the PDZ protein Tax-interacting protein-1 (TIP-1) and its recognition peptide (PDZ-pep) derived from beta-catenin was performed using an atomic force microscope (AFM), together with measurement of thermodynamic and kinetic parameters using surface plasmon resonance (SPR). The unbinding force of this pair was measured under different conditions of AFM tip retraction velocity. The relationship between the unbinding force and the logarithmic force-loading rate, that is, the dynamic force spectrum, exhibited two different rate regimes, for each of which the forces increased linearly with the force-loading rate. On the basis of the theoretical treatment of the Bell Evans model, the positions of two different activation barriers in the reaction coordinate and dissociation rate constants in each barrier were evaluated from slopes and x-intercepts of the two linear regimes (first barrier: 0.04 nm and 1.10 x 10 s(-1); second barrier: 0.21 nm and 2.77 x 10(-2) s(-1), respectively). Although two-step unbinding kinetics between TIP-1 and PDZ-pep was suggested from the DFS analysis, SPR results showed single-step dissociation kinetics with a rate constant of 2.89 x 10(-1) s(-1). Different shapes of the free energy profile of the unbinding process were deduced from each result of DFS and SPR. The reason for such topographic differences in the energy landscape is discussed in relation to the differences in the pathways of forced unbinding and spontaneous dissociation. PMID- 17269806 TI - Carbon nanotube capsules self-assembled by w/o emulsion technique. AB - Carbon nanotube capsules (CNCs) with the diameter of 5-10 microm were fabricated from acid-modified multiwalled carbon nanotubes (CNTs) using water-in-oil (W/O) emulsion technique. The effects of the content of CNTs in water, the extent of acid treatment, and the length of CNTs used on the formation and morphology of CNCs were investigated. It was found that the amount of CNTs in water and the length of CNTs are the crucial factors for the formation of carbon nanotube capsules. PMID- 17269805 TI - Understanding the oxidative stability of gold monolayer-protected clusters in the presence of halide ions under ambient conditions. AB - We report on the oxidative stability of thiol-passivated Au monolayer-protected clusters (MPCs) made via a modified Brust-Schiffrin method. A sequential oxidation of the anchored thiol groups to disulfide and sulfonate groups and the oxidation of Au atoms to Au3+ species is observed upon exposure of Au MPCs to air in the presence of halide anions. In addition, the average nanoparticle size grows via aggregation of the MPCs, leading eventually to partial oxidation of the Au MPCs and precipitation of the remaining nanoparticles from solution or to complete oxidation of the gold atoms at high halide concentrations. These results show that Au MPCs are prone to oxidation in air in the presence of halide anions, and therefore, particles made using phase transfer reagents such as tetraoctylammonium bromide must be thoroughly removed to avoid particle size growth, oxidation, and precipitation of the Au MPCs. In addition, for biological applications involving Au MPCs, care must be taken to ensure that oxidation of MPCs in air is not problematic when working in media containing halide anions. PMID- 17269807 TI - Colloidal phase separation of concentrated PNIPAm solutions. AB - In the concentration range of 1-6 wt %, solutions of a thermosensitive polymer (poly-N-isopropylacrylamide (PNIPAm), Mw = 1.4 x 10(5) g.mol(-1)) are shown to phase separate in the form of dense stable colloids of nearly pure polymer. Diffuse wave spectroscopy and small-angle neutron scattering both provide consistent measurements of the colloidal size as a function of temperature. Results are in agreement with a Cahn regime of spinodal decomposition blocked at an early stage, prior to a growth that would lead to a macroscopic phase separation. [Early results of this work were presented at the 231st American Chemical Society National Meeting, Symposium on Amphiphilic Polymers, Atlanta, GA, 2006, March 26-30.]. PMID- 17269808 TI - UVO-tunable superhydrophobic to superhydrophilic wetting transition on biomimetic nanostructured surfaces. AB - A novel strategy for a tunable sigmoidal wetting transition from superhydrophobicity to superhydrophilicity on a continuous nanostructured hybrid film via gradient UV-ozone (UVO) exposure is presented. Along a single wetting gradient surface (40 mm), we could visualize the superhydrophobic (thetaH2O > 165 degrees and low contact angle hysteresis) transition (165 degrees > thetaH2O > 10 degrees ) and superhydrophilic (thetaH2O < 10 degrees within 1 s) regions simply through the optical images of water droplets on the surface. The film is prepared through layer-by-layer assembly of negatively charged silica nanoparticles (11 nm) and positively charged poly(allylamine hydrochloride) with an initial deposition in a fractal manner. The extraordinary wetting transition on chemically modified nanoparticle layered surfaces with submicrometer- to micrometer-scale pores represents a competition between the chemical wettability and hierarchical roughness of surfaces as often occurs in nature (e.g., lotus leaves, insect wings, etc). PMID- 17269809 TI - Preparation and characterization of self-assembled nanoparticles formed by poly(ethylene oxide)-block-poly(epsilon-caprolactone) copolymers with long poly(epsilon-caprolactone) blocks in aqueous solutions. AB - Aqueous solutions of self-assembled nanoparticles formed by biocompatible diblock copolymers of poly(epsilon-caprolactone)-block-poly(ethylene oxide) (PCL-PEO) with the same molar mass of the PEO block (5000 g mol-1) and three different molar masses of the PCL block (5000, 13 000, and 32 000 g mol-1) have been prepared by a fast mixing the copolymer solution in a mild selective solvent, tetrahydrofuran (THF)/water, with an excess of water, that is, by quenching the reversible micellization equilibrium, and a subsequent removal of THF by dialysis of the water-rich solution against water. The prepared nanoparticles have been characterized by static and dynamic light scattering and atomic force microscopy imaging. It was found that stable monodisperse nanoparticles are formed only if the initial mixed solvent contained 90 vol % THF. The results show that the prepared nanoparticles are spherical vesicles with relatively thick hydrophobic walls, that is, spherical core/shell nanoparticles with the hollow core filled with the solvent. PMID- 17269810 TI - Automated preparation method for colloidal crystal arrays of monodisperse and binary colloid mixtures by contact printing with a pintool plotter. AB - Photonic crystals and photonic band gap materials with periodic variation of the dielectric constant in the submicrometer range exhibit unique optical properties such as opalescence, optical stop bands, and photonic band gaps. As such, they represent attractive materials for the active elements in sensor arrays. Colloidal crystals, which are 3D gratings leading to Bragg diffraction, are one potential precursor of such optical materials. They have gained particular interest in many technological areas as a result of their specific properties and ease of fabrication. Although basic techniques for the preparation of regular patterns of colloidal crystals on structured substrates by self-assembly of mesoscopic particles are known, the efficient fabrication of colloidal crystal arrays by simple contact printing has not yet been reported. In this article, we present a spotting technique used to produce a microarray comprising up to 9600 single addressable sensor fields of colloidal crystal structures with dimensions down to 100 mum on a microfabricated substrate in different formats. Both monodisperse colloidal crystals and binary colloidal crystal systems were prepared by contact printing of polystyrene particles in aqueous suspension. The array morphology was characterized by optical light microscopy and scanning electron microscopy, which revealed regularly ordered crystalline structures for both systems. In the case of binary crystals, the influence of the concentration ratio of the large and small particles in the printing suspension on the obtained crystal structure was investigated. The optical properties of the colloidal crystal arrays were characterized by reflection spectroscopy. To examine the stop bands of the colloidal crystal arrays in a high-throughput fashion, an optical setup based on a CCD camera was realized that allowed the simultaneous readout of all of the reflection spectra of several thousand sensor fields per array in parallel. In agreement with Bragg's relation, the investigated arrays exhibited strong opalescence and stop bands in the expected wavelength range, confirming the successful formation of highly ordered colloidal crystals. Furthermore, a narrow distribution of wavelength-dependent stop bands across the sensor array was achieved, demonstrating the capability of producing highly reproducible crystal spots by the contact printing method with a pintool plotter. PMID- 17269811 TI - Covalent formation of nanoscale fullerene and dendrimer patterns. AB - Localized patterns of amine-terminated monolayers obtained via the surface modification of a monolayer with the biased probe of an atomic force microscope were used to covalently attach buckminsterfullerene or dendrimers to the surface, affording lines as narrow as 20 nm. PMID- 17269813 TI - Room-temperature imprinting poly(acrylic acid)/poly(allylamine hydrochloride) multilayer films by using polymer molds. AB - Layer-by-layer assembled polyelectrolyte multilayer films of poly(acrylic acid) (PAA)/poly(allylamine hydrochloride) (PAH) have been successfully patterned by room-temperature imprinting using a Norland Optical Adhesives (NOA 63) polymer mold. The proper amount of water in the PAA/PAH multilayer film can decrease the viscosity of the film and facilitate the imprinting. Many factors, such as imprinting pressure, length of imprinting time, and the structure and size of the patterns in the polymer mold, can produce an influence on the final imprinted pattern structures on multilayer films. A high imprinting pressure of 100 bar and elongated imprinting time of several hours is needed to achieve a patterned PAA/PAH multilayer film with a feature size of several tens of micrometers. With a twice imprinting, grid structures can be successfully produced when a NOA 63 mold having line structures is used. Room-temperature imprinting by using polymer NOA 63 mold provides a facile way to fabricate layered polymeric films with various kinds of pattern structures. PMID- 17269812 TI - Salt-induced micellization of a triblock copolymer in aqueous solution: a 1H nuclear magnetic resonance spectroscopy study. AB - An aqueous micellar solution of a PEO-PPO-PEO triblock copolymer, pluronic F88 (EO103PO39EO103), in the presence of salt (KCl) has been investigated by 1H NMR spectroscopy. The hydrogen-bonding structure in water is directly changed by the strong polarization effect of added salt, which indirectly weakens the interaction of polymer molecules with water. Both EO and PO blocks are dehydrated by the addition of salt in a similar way, whereas the solubility of the PO blocks may be affected in a more pronounced way, which results in the decrease of the critical micellization temperature (CMT). It is found that the addition of salt favors a more compact micellar core, where the water content is decreased and an effective PO-PO interaction is increased. Increasing the salt concentration would result in a decrease in the number of gauche conformers in the PPO chain, which may be the deeper reason for the decreasing solubility of PPO segments in aqueous salt solution. The temperature region over which the micellization occurs is broad, indicating that micelles and unimers coexist over an extended temperature range, whereas this transition region is significantly narrowed by the addition of salt. The addition of salt offers a good substitute way of changing the temperature to induce micellization. The critical micellization salt concentration (CMSC) is determined to be 1.0 mol l-1 for KCl in 2.5% aqueous pluronic F88 solution at 25 degrees C, and the transition region in which both free and associated copolymer molecules coexist is defined to range from 1 to 2 mol L-1. PMID- 17269815 TI - Nanoporous crystal 12CaO.7Al2O3: a playground for studies of ultraviolet optical absorption of negative ions. AB - A novel nanoporous material 12CaO.7Al2O3 (C12A7) offers a possibility of incorporating large concentrations (>1021 cm-3) of a wide range of extraframework anions inside its nanopores. We have investigated, both experimentally and theoretically, optical absorption associated with several types of such anions, including F-, OH-, O-, O2-, O2-, and O22-, and assigned their optical absorption bands. It is demonstrated that the chemical identity and concentration of extraframework anions can be controlled by an appropriate treatment of "as grown" C12A7. We also show that the position of the adsorption edge is, in turn, determined by the chemical identity of the extraframework species and can be varied in the range of approximately 4-6 eV. We suggest that C12A7 is a unique host material, which can be used as a playground for studying negatively charged species that are unstable in other environments. PMID- 17269814 TI - Solvation free energy of amino acids and side-chain analogues. AB - The solvation free energies of amino acids and their side-chain analogues in water and cyclohexane are calculated by using Monte Carlo simulation. The molecular interactions are described by the OPLS-AA force field for the amino acids and the TIP4P model for water, and the free energies are determined by using the Bennett acceptance method. Results for the side-chain analogues in cyclohexane and in water are used to evaluate the performance of the force field for the van der Waals and the electrostatic interactions, respectively. Comparison of the calculated hydration free energies for the amino acid analogues and the full amino acids allows assessment of the additivity of the side chain contributions on the number of hydrating water molecules. The hydration free energies of neutral amino acids can be reasonably approximated by adding the contributions of their side chains to that of the hydration of glycine. However, significant nonadditivity in the free energy is found for the zwitterionic form of amino acids with polar side chains. In serine and threonine, intramolecular hydrogen bonds are formed between the polar side chains and backbone groups, leading to weaker solvation than for glycine. In contrast, such nonadditivity is not observed in tyrosine, in which the hydroxyl group is farther separated from, and therefore cannot form an intramolecular hydrogen bond with, the backbone. For histidine we find that a water molecule can form a bridge when the intramolecular hydrogen bond between the polar group and the backbone is broken. PMID- 17269816 TI - Van der waals-like isotherms in a confined electrolyte by spherical and cylindrical nanopores. AB - Electrolytes confined by spherical, cylindrical, and slit-like charged nanopores are studied. Results for ionic distribution profiles, pressures of the confined fluid, and absorption isotherms are obtained through the hypernetted chain/mean spherical approximation (HNC/MSA) integral equations theory. In spherical and cylindrical geometries, an inward, non-monotonic behavior of the pressure is found as confinement increases, implying a negative compressibility. The pressure vs volume isotherms resemble liquid-vapor van der Waals-like phase transition diagrams. This effect is correlated with a charge separation inside a spherical pore previously reported (Phys. Rev. Lett., 79, 3656, 1997). Here, the mechanism of charge separation and negative compressibility are explored in detail. When compared with the slit-like pore pressure, important qualitative differences are found. PMID- 17269817 TI - Temporal modulation of a spatially periodic potential for kinetically governed oriented motion. AB - This theoretical paper introduces an experimental protocol derived from the concept of Brownian motors in order to selectively confer an oriented motion to given charged reactants. Instead of maintaining permanently the system in nonequilibrium conditions, we propose a simple experimental trick to restore periodically a transient out-of-equilibrium regime: the reactive medium is alternately submitted to a sawtooth potential and to a potential ramp. The model provides approximate analytical expressions for the operating conditions allowing us to design the extraction from a mixture of any desired reactant characterized by its rate constants. The orders of magnitude suggest a possible implementation in microsystems where the present approach could be used for separation and analysis. PMID- 17269818 TI - Ultrafast dynamics of room temperature ionic liquids after ultraviolet femtosecond excitation. AB - The photochemistry and relaxation dynamics of four room-temperature ionic liquids (RTILs) after ultraviolet (UV) photolysis were investigated by femtosecond pump probe absorption spectroscopy. A pulse duration-limited rise of the induced absorption in halide-containing RTILs at various probe wavelengths was attributed to the generation of solvated electrons. With continuous irradiation (static conditions), di- and trihalide ion formation became apparent especially below 1000 nm. The formation of trihalide ions was further confirmed by steady-state UV absorption spectroscopy. All RTILs showed a rich photochemistry after UV photolysis leading to the build-up of various long-lived intermediate products as evidenced from the observation that ionic liquids turn yellow upon continuous irradiation. On the other hand, exposing RTILs to the excitation pulse for a short time (rapid-scan method) significantly suppressed the formation of halides. The results suggest that the development of flow-cell systems for highly viscous ionic liquids is urgently needed to quantitatively investigate their ultrafast dynamics. PMID- 17269819 TI - Color-tunable, aggregation-induced emission of a butterfly-shaped molecule comprising a pyran skeleton and two cholesteryl wings. AB - A chiral pyran derivative containing two cholesteryl groups (1) is synthesized, and its optical properties are investigated. Whereas the isolated molecule of 1 is virtually nonluminescent in dilute solutions, it becomes highly emissive with a 2 orders of magnitude increase in fluorescence quantum yield upon aggregation in poor solvents or in solid state, showing a novel phenomenon of aggregation induced emission (AIE). The color and efficiency of the AIE of 1 can be tuned by varying the morphology of its aggregates: photoluminescence of its aggregates formed in a tetrahydrofuran/water mixture progressively red-shifts (green --> yellow --> red) with increasing water content of the mixture, with the crystalline aggregates emitting bluer lights in higher efficiencies than their amorphous counterparts. PMID- 17269820 TI - Synthesis of carbon encapsulated magnetic nanoparticles with giant coercivity by a spray pyrolysis approach. AB - Carbon encapsulated magnetic (metal) nanoparticles (CEMNPs) have wide applications in biomedicine and the magnetic recording industry. However, synthesis of such particles with a high coercive force and good ferromagnetism is still a great challenge. The present study reports a new method for the continuous production of CEMNPs of high purity. This involves the spray pyrolysis of a mixture of iron pentacarbonyl and ethanol at 500-900 degrees C. Results show that the Fe (or Fe3C) particles synthesized at 700 and 900 degrees C were well encapsulated by graphitic layers with rare byproducts such as carbon nanotubes, nanofibers, or bulk amorphous carbon. Those synthesized at 700 degrees C had a particle size of 30-50 nm, a giant coercive force of 867 Oe, and a good magnetic remanence of 33% at room temperature. The present approach based on spray pyrolysis is advantageous over previous ones in suitability for large-scale production, and the synthesized material has wide applications in many fields. PMID- 17269821 TI - Biological systems as nanoreactors: anomalous small-angle scattering study of the CdS nanoparticle formation in multilamellar vesicles. AB - The formation of cadmium sulfide (CdS) particles in the gaps between the layers of the multilamellar vesicles is described, introducing a new pathway in the preparation of nanometer-scale particles. The in situ structural characterization of both the CdS particles and the vesicles as a reaction medium was performed in the early and final states of the process by using anomalous small-angle X-ray scattering (ASAXS) and freeze-fracture methods. The ASAXS method provides the separation of the scattering of nanoparticles present in a small amount, whereby the monitoring of their formation and growth in the whole time range of manufacturing has become possible. PMID- 17269823 TI - Coumaroyl iridoids and a depside from cranberry (Vaccinium macrocarpon). AB - Cranberry (Vaccinium macrocarpon) juice has been used for urinary tract infections for approximately 50 years. Recent research suggests that this botanical blocks adherence of pathogenic E. coli to urinary tract cells, thus preventing infection. While current evidence indicates that proanthocyanidins are responsible for this activity, these compounds may not reach the urinary tract; thus further investigation is warranted. Fractionation of cranberry juice concentrate was guided by a recently published antiadherence assay, and the resulting fractions were phytochemically characterized. Two new coumaroyl iridoid glycosides, 10-p-trans- (1) and 10-p-cis-coumaroyl-1S-dihydromonotropein (2), and a depside, 2-O-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylmethylacetate (3), were isolated, and although these compounds did not have antiadherent activity in isolation, they might constitute a new group of marker compounds for this active fraction of cranberry. PMID- 17269822 TI - Multilayered films fabricated from an oligoarginine-conjugated protein promote efficient surface-mediated protein transduction. AB - The conjugation of cationic protein transduction domains to proteins results in an increase in the extent to which proteins are internalized by cells. This investigation sought to determine whether the conjugation of a protein transduction domain to a functional protein could be used to facilitate the incorporation of the protein into multilayered polyelectrolyte films and, subsequently, whether these films could be used to promote surface-mediated protein transduction. We demonstrate that it is possible to fabricate multilayered assemblies 80 nm thick using sodium polystyrene sulfonate (SPS) and bovine pancreatic ribonuclease (RNase A) conjugated to the cationic protein transduction domain nonaarginine (R(9)) using an entirely aqueous layer-by-layer process. We demonstrate further that the conjugation of R(9) to RNase A permits the assembly of multilayered films under conditions that do not allow for the incorporation of the unmodified protein. This result suggests that R(9) functions as a cationic anchor and serves to increase the strength of electrostatic interactions with SPS and facilitate layer-by-layer assembly. We also demonstrate that RNase A-R(9)/SPS films dissolve rapidly in physiologically relevant media and that macroscopic objects coated with these materials can be used to mediate high levels of protein transduction in mammalian cells. These results suggest the basis of general methods that could contribute to the design of materials that permit spatial and temporal control over the delivery of therapeutic proteins to cells and tissues. PMID- 17269824 TI - Lissoclibadins 4-7, polysulfur aromatic alkaloids from the Indonesian ascidian Lissoclinum cf. badium. AB - Four new polysulfur aromatic alkaloids, lissoclibadins 4 (1), 5 (2), 6 (3), and 7 (4), were isolated from the ascidian Lissoclinum cf. badium collected in Indonesia, together with seven known alkaloids, lissoclibadins 1 (5), 2 (6), and 3 (7), lissoclinotoxins E (8) and F (9), 3,4-dimethoxy-6-(2'-N,N dimethylaminoethyl)-5-(methylthio)benzotrithiane (10), and N,N-dimethyl-5 (methylthio)varacin (11). Compounds 1-11 were isolated from the ascidian collected in March (wet season), while 5-11 have been obtained previously from the organism collected in September (dry season) at the same site. The structures of the new compounds were assigned on the basis of their spectroscopic data. Lissoclibadins 4-7 (1-4) inhibited the colony formation of Chinese hamster V79 cells with EC50 values of 0.71, 0.06, 0.06, and 0.17 microM, respectively. Compounds 1-4 showed also weak antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Saccharomyces cerevisiae. PMID- 17269825 TI - Paecilodepsipeptide A, an antimalarial and antitumor Cyclohexadepsipeptide from the insect pathogenic fungus Paecilomyces cinnamomeus BCC 9616. AB - Paecilodepsipeptide A (1), a new cyclohexadepsipeptide possessing three d-amino acid residues, together with its linear analogues paecilodepsipeptides B (2) and C (3), was isolated from the insect pathogenic fungus Paecilomyces cinnamomeus BCC 9616. Structures of these compounds were elucidated primarily by NMR and mass spectroscopic analyses. The absolute configurations of the amino acid and hydroxy acid residues of 1 were addressed by HPLC analysis of its acid hydrolyzate using a chiral column and Marfey's method. Paecilodepsipeptide A (1) showed activity against the malarial parasite Plasmodium falciparum K1 with an IC50 value of 4.9 microM. This compound also showed cytotoxicity to two cancer cell lines, KB (IC50 5.9 microM) and BC (IC50 6.6 microM); however, it was inactive against noncancerous Vero cells up to 67 microM (50 microg/mL). PMID- 17269826 TI - Variable Markovnikov orientation and "cis effect" in ene reactions of nitrosocarbonyl intermediates. AB - Nitrosocarbonyl intermediates, generated at room temperature by the mild oxidation of nitrile oxides, undergo clean ene reactions with trisubstituted olefins. Allylic hydrogens on the more congested side of the alkene are exclusively abstracted (the "cis effect"), thus resembling singlet oxygen behavior. Nitrosocarbonyl benzene follows a Markovnikov orientation and abstracts preferentially the twix hydrogens over the lone ones. With the more sterically demanding nitrosocarbonyl mesitylene, the Markovnikov directing effect is relieved, and comparable twix and lone abstraction are observed. PMID- 17269827 TI - Construction of bicyclic ring systems via a transannular SmI2-mediated ketone olefin cyclization strategy. AB - The development of novel methods and strategies for the formation of polycyclic ring structures is of utmost importance in organic synthesis. The present study describes the investigation of a transannular cyclization strategy for constructing bicyclic ring systems. To test the viability of the approach, the SmI2-mediated ketone-olefin coupling reaction, a method previously developed in this laboratory, was examined. Investigation of the transannular cyclization of cyclooctene, cyclodecene, and cycloundecene derivatives revealed that the process proceeds with high yield and diastereoselectivity, and in the case of larger ring sized compounds, with excellent regioselectivity. The regioselectivity of the annulation process could be rationalized based on examining the low energy conformations of the keto alkene starting materials. These results demonstrate the efficiency and the potential of the transannular cyclization tactic for the creation of bicyclic ring systems. PMID- 17269828 TI - Sodium bicarbonate-catalyzed stereoselective isomerizations of electron-deficient propargylic alcohols to (Z)-enones. AB - Redox isomerization is a synthetically important process because it creates two new functional groups in the product, among which is the isomerization of propargylic alcohols to conjugated enones. Although E-enones have been prepared by this approach, Z-enones could not be accessed. We previously reported DABCO catalyzed E-selective isomerization of electron-deficient propargylic alcohols to enones and its mechanism. Based on this mechanism, we have now developed the first Z-selective redox isomerization of electron-deficient propargylic alcohol to enone using sodium bicarbonate as a catalyst. PMID- 17269829 TI - Synthesis and DNA cleavage activity of artificial receptor 1,4,7 triazacyclononane containing guanidinoethyl and hydroxyethyl side arms. AB - A novel phosphodiester receptor 1-(2-guanidinoethyl)-4-(2-hydroxyethyl)-1,4,7 triazacyclononane hydrochloride 1 was synthesized. DNA cleavage efficiency of 1 exhibits remarkable increases compared with its ZnII complex and corresponding nonguanidinium compound N-(2-hydroxyethyl)-1,4,7-triazacyclononane and parent 1,4,7-triazacyclononane. Kinetic data of DNA cleavage promoted by 1 fit to a Michaelis-Menten-type equation with kmax of 0.160 h-1 giving 107-fold rate acceleration over uncatalyzed DNA. The acceleration is driven by the spatial proximity of the nucleophilic hydroxyl group and the electrophilic activation for the phosphodiester by the guanidinium group. PMID- 17269830 TI - Pectenotoxin-2 synthetic studies. 3. Assessment of the capacity for stereocontrolled cyclization to form the entire C1-C26 subunit based upon the double bond geometry across C15-C16. AB - Second-generation synthetic routes to enantiopure sulfone 21 and aldehyde 24 are described. The union of these two intermediates by means of a Julia-Kocienski coupling gave rise to a series of E-configured building blocks that did not prove amenable to transannular cyclization. Alternatively, when the C15-C16 double bond was introduced with Z-geometry by Wittig olefination, spontaneous closure to generate a tetrahydrofuran culminated an ensuing direct dihydroxylation step. The structural assignment to 35, undergirded by detailed 1H and 13C NMR studies, is consistent with proper transannular bonding so as to deliver the entire C1-C26 fragment of PTX2. PMID- 17269831 TI - Observing catalysis through the agency of the participating electrons: surface chemistry-induced current changes in a tin oxide nanowire decorated with silver. AB - Conductometric measurements were performed on single tin oxide nanowires with and without Ag nanoparticle surface decoration, in flowing oxygen/ethylene mixtures of varying composition. Ag-decorated nanowires showed a significant ethylene effect, which we explain in terms of the modification of the Schottky junction formed between the Ag particles and the tin oxide, resulting from the surface chemical processes involving ethylene and oxygen occurring exclusively on the silver nanoparticles' surface. Assuming the observed temperature dependence of these ethylene-induced current decrements reflect changes in the steady-state concentration of ethylene, oxygen, and a surface intermediate that ultimately leads to ethylene oxide, one calculates the enthalpy for the production of the reaction intermediate to be approximately -4.6 kcal/mol, of the right order of magnitude as the calculated value reported in the literature for the formation of a putative ethylene oxametallacycle intermediate in the ethylene epoxidation reaction. Our results illustrate how fundamental catalytic processes occurring at metal nanoparticle surfaces can significantly influence the electronic properties of oxide nanowires used as metal particle supports. PMID- 17269832 TI - Cell-free co-synthesis of protein nanoassemblies: tubes, rings, and doughnuts. AB - We used a cell-free transcription/translation system to synthesize structural proteins of the T4 bacteriophage. We focused on two proteins that participate in the formation of the virus tail tube assembly. Synthesized separately, the proteins assembled into their in vivo forms, namely one polymerized into rigid hollow nanotubes approximately 20 nm thick and hundreds of nanometers long, the other assembled into 10 nm tube-capping hexameric rings. Co-synthesis of the two proteins, however, revealed a novel structure of a nanodoughnut with an outer diameter of approximately 50 nm and thickness of approximately 20 nm. Cell-free co-synthesis and assembly of T4 structural proteins can be extended in a combinatorial fashion. The addition of other structural genes offers control of native nanoassemblies and may reveal ones not observable by mixing purified components. PMID- 17269833 TI - Effects on resource utilization of adding salmeterol in combination or separately to inhaled corticosteroids. AB - BACKGROUND: The addition of a long-acting beta-agonist (LABA) to an inhaled corticosteroid (ICS) for patients with moderate or severe persistent asthma improves outcomes such as pulmonary function, reduces exacerbations requiring oral steroids, and reduces use of rescue beta-agonists. OBJECTIVE: To assess the key resource utilization outcomes of adding salmeterol, a LABA, to fluticasone, an ICS, either as a fixed-combination inhaler (fluticasone-salmeterol [FSA] or as a separate inhaler used concomitantly with the ICS beclomethasone (BSA). METHODS: This is a retrospective, observational database study that extracted data from electronic medical and prescription records in which the prescription written was identical to the prescription dispensed. The sample included asthmatic patients aged 12 to 55 years who received a medium dose of an ICS (240-480 mcg of beclomethasone, 264-660 mcg of fluticasone, 600-1,200 mcg of budesonide, or 1,000 2,000 mcg of triamcinolone acetonide) between July 2001 and December 2002 and had salmeterol added to the regimen (index date). From this population of patients, the analytical cohort was derived to include 1,213 patients who received FSA and a matched cohort of 1,213 patients who received BSA. The primary endpoint was an asthma-related event (ARE), which was defined as (1) an emergency department (ED) visit or (2) hospital admission with a primary asthma diagnosis code (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 493.xx). The secondary endpoints were the (1) use of short-acting beta-agonist (SABA) equivalents, (2) percentage of patients who received 1 or more oral steroid prescriptions, (3) patterns of ICS use, and (4) refill rates of salmeterol. All data were collected for 6 months before and 6 months after the index date, defined as the first prescription dispensed to the patient that included salmeterol as an ingredient. RESULTS: Outcomes were improved in both cohorts with no significant difference in the likelihood of an ARE, 60 patients (4.9%) for FSA and 90 patients (8.1%) for BSA (odds ratio [OR], 0.668; 95% confidence interval [CI], 0.443-1.008); P=0.055). FSA was associated with a reduction in AREs of 55% (10.9%-4.9%; P <0.001), and BSA with a reduction in AREs of 39% (13.3%-8.1%; P <0.001). FSA compared with BSA was associated with a greater reduction in SABA use (-0.66 canister equivalents over 6 months, P <0.001) and a lower likelihood of filling an oral steroid prescription, 35.8% of FSA patients compared with 38.0% of BSA patients (OR, 0.801; 95% CI, 0.662-0.970; P=0.023). For the 132 FSA patients (10.9%) and 162 BSA patients (13.4%) who had an ARE in the preperiod, those who received FSA in the postperiod had a 47% lower likelihood of a subsequent ARE, 17.4% of 132 patients compared with 27.8% of 162 BSA patients (OR, 0.527; 95% CI, 0.291-0.954; P=0.034). No ARE differences in subgroup analyses were noted for patients without an ARE in the preperiod or for patients using more than 6 canisters of SABA. More patients in the FSA group took daily doses of 400 mcg or more of ICS than those in the BSA group (32.0% compared with 10.0%, P <0.001). The average refill rate for salmeterol was 2.71 prescriptions (SD=1.42) over 6 months for FSA compared with 2.38 (SD=1.49) for BSA (P <0.001). CONCLUSION: Overall, the addition of salmeterol as a fixed combination with fluticasone or with beclomethasone as separate inhalers was associated with a reduction in the ARE rate. Patients who received FSA were more likely to be exposed to a higher dose of ICS compared with those who received BSA. Differences in resource utilization may be attributed to how these drugs are prescribed and taken by patients in a real-practice (naturalistic) setting rather than to any inherent difference between the drugs (i.e., higher ICS dose rather than greater efficacy). PMID- 17269834 TI - Adherence to clinical practice guidelines for 7 chronic conditions in long-term care patients who received pharmacist disease management services versus traditional drug regimen review. AB - BACKGROUND: Numerous studies have shown that adherence to published clinical practice guidelines (CPGs) reduces disease morbidity and mortality. However, few benchmarks exist that demonstrate the rate of adherence to CPGs in patients in long-term-care facilities (LTCFs). OBJECTIVE: To evaluate CPG adherence in patients in LTCFs who received consultation from pharmacists who emphasize disease state management (DSM) compared with patients in other LTCFs who received traditional drug regimen review (DRR). METHODS: A retrospective chart review was conducted in November 2005 for 107 patients who received DSM services in 2 LTCFs and 304 patients who received DRR services in 4 LTCFs for the service period ending September 30, 2005. Chart review was conducted on all patients included in the current census as of September 1, 2005; residents were excluded from the analysis if they were discharged or deceased between September 1, 2005, and the date of chart review. CPG adherence was evaluated for the following 7 conditions: diabetes, coronary artery disease (CAD), stroke, heart failure (HF), hypertension, hyperlipidemia, and osteoporosis. In addition, the 6 most recent pharmacist recommendations for each patient were classified according to disease state. RESULTS: Adherence to CPGs was significantly better (all P <0.05) in patients receiving DSM services for the following performance measures for 4 of the 7 disease states: (1) diabetes: antiplatelet or warfarin use or contraindication for use (hypersensitivity or history of serious bleeding event), 89.7% for DSM services versus 71.0% for DRR services, and glycosylated hemoglobin (HbA1c) 0.05). The mean number of pharmacist recommendations per patient per month was greater in DSM facilities (0.76) compared with DRR facilities (0.23, P <0.001). Pharmacists who provided DSM consultant services were more likely to make a recommendation to improve DSM (51.6%) than were pharmacists in the comparison facilities who provided traditional DRR services (31.7%, P <0.001). CONCLUSION: This self-evaluation of the provision of pharmacist consultant services that focus on disease management in addition to DRR found a higher rate of adherence to clinical practice guidelines for 4 of 7 common chronic disease states in long-term-care patients compared with patients who received only traditional DRR services. PMID- 17269835 TI - AMCP Format dossier requests: manufacturer response and formulary implications for one large health plan. AB - BACKGROUND: The Academy of Managed Care Pharmacy (AMCP) Format for Formulary Submissions, a template for health plans to use in developing formulary submission guidelines, has been widely adopted since its initial release in 2000. Many health plans request a dossier (a standardized set of clinical and economic evidence prepared by pharmaceutical manufacturers) to provide information for consideration during the formulary decision-making process. While dossier quality has reportedly improved over time, there is no recent research examining the response rate to dossier requests and the quality of dossiers received. OBJECTIVE: To perform an evaluation of pharmaceutical manufacturers. response to a request for a product dossier prepared using the AMCP Format, and to determine if dossier receipt was associated with a favorable formulary placement. METHODS: The pharmacy and therapeutics (P&T) committee of a mid-Atlantic health plan with approximately 3 million members reviewed 43 drug products from February 2004 through December 2005. A university-based clinical evaluation subcontractor requested dossiers in the AMCP Format by telephone and e-mail from the manufacturers. drug information center about 8 weeks before the committee meeting. A retrospective evaluation of the materials received from the manufacturers was performed. A logistic regression model was developed to determine if dossier receipt increased the likelihood of second-tier copayment formulary placement for new product reviews. RESULTS: Dossiers were requested for 43 products. We received dossiers for 25 products (58%), other drug information (e.g., journal reprints, product labeling) for 10 products (23%), a formulary kit for 4 products (9%), and no response for the remaining 4 products (9%). Of the 25 dossiers, 21 (84%) generally followed the AMCP Format. Unlocked interactive budget impact models were included in 5 dossiers (20%), and modeling reports (without an unlocked interactive model) were included in 12 dossiers (48%). Dossiers were more likely to be received when the time between U.S. Food and Drug Administration (FDA) approval and dossier request was >/- 4 months (65% vs. 27% when <4 months; P <0.05) and when requested from a large manufacturer (top 25 in sales) compared with smaller manufacturers (75% vs. 43%; P <0.05). Dossier receipt did not improve a product.s likelihood for preferred formulary placement; none of the new products for which dossiers were received were assigned to the second copayment tier compared with 33% of the new products with no supporting dossier. The logistic regression model failed to find any correlation between dossier receipt and preferred formulary placement. CONCLUSIONS: Manufacturers met the request for a dossier nearly three fifths of the time. The dossiers were of high quality and generally followed the AMCP Format; the models included in dossiers varied widely in their design and utility. The product manufacturer.s size and the time between FDA approval and dossier request influenced the likelihood of dossier receipt. Receipt of a dossier did not appear to influence the likelihood of a product attaining preferred formulary status. PMID- 17269836 TI - Descriptive analysis of the direct medical costs of multiple sclerosis in 2004 using administrative claims in a large nationwide database. AB - BACKGROUND: Multiple sclerosis (MS) is chronic and debilitating, afflicts patients in the prime of their lives, and requires costly, decades-long disease management. MS prevalence is increasing, and treatment with new drug therapies is expensive. OBJECTIVES: The objectives of this analysis were to (1) determine the average total and component direct medical costs incurred in the treatment of MS patients in 2004, and (2) compare MS treatment costs and cost factors in 2004 with 1995. METHODS: The data for this analysis were abstracted from the PharMetrics Integrated Patient-centric Database, which contains administrative claims data from more than 80 private and public health plans in the United States, representing more than 9.6 million unique patients in 2004. To be included in this analysis, each patient had to have at least 1 medical claim with a diagnosis of MS (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 340) in the date of service period from January 1, 2004, through December 31, 2004. Patients were segmented according to patient age and sex, comorbid conditions, payer type, and use of specific types of disease-modifying drugs (DMDs). Episode Treatment Group (ETG) software (ETG numbers 149 or 150) was used to aggregate medical claims related to MS since not all MS-related medical claims have the ICD-9-CM code 340. ETGs are commonly used to aggregate administrative claims data and to define discrete periods of care (episodes); this study used ETGs only to aggregate administrative claims. Statistical comparisons were subsequently performed using analysis of variance and chi-square analyses. The source of the data for the aggregate MS treatment costs in 1995 was the Medstat MarketScan database. RESULTS: In calendar year 2004, a total of 13,420 patients were identified with a medical or hospital claim with ICD-9-CM code 340, a prevalence of approximately 14.0 per 10,000. The final study population was reduced to 10,099 patents (75.3%) after applying the criterion of 12 full months of available claims data. The total average annual cost for the 10,099 MS patients in 2004 was $12,879 (standard deviation, $18,582), 64.8% of which was attributable to the cost of prescription drugs and 61.4% to the cost of DMDs in particular, 26.2% to outpatient care, 7.8% to inpatient care, and 1.1% to emergency room visits. There was no difference in total average annual medical costs for males compared with females, but costs did differ among age categories and by insurance type and payer. A total of 5,810 patients (57.5% of the study population) reported at least 1 pharmacy claim for a DMD, and these patients had average annual costs of $18,944 compared with $4,662 total annual costs for MS patients who did not receive DMDs. Pharmacy costs represented 75.3% of annual medical costs for the patients who reported at least 1 pharmacy claim for a DMD but only 7.4% for patients who did not receive DMDs. A comparison of 2004 costs with 1995 costs (adjusted for 2004 based on the Consumer Price Index; CPI-U [All Urban Consumers, All Items]; 1982-84=100) demonstrated that total annual MS-related treatment costs increased by 35%, from $9,515 in 1995 to $12,879 in 2004. There was some difference in total annual MS-related treatment costs in 2004 among the 4 DMD therapy groups.$16,928 for glatiramer, $17,987 for IFN beta-1a (intramuscular), $19,616 for IFN beta-1b, and $22,557 for IFN beta-1a (subcutaneous), P <0.001. CONCLUSION: Pharmacy costs accounted for 65% of total MS-related medical costs in 2004 and 75% of total costs for the subset of MS patients(58%) who received at least 1 DMD. PMID- 17269837 TI - Use of low-molecular-weight heparin during dental extractions in a medicaid population. AB - BACKGROUND: Evidence-based guidelines recommend against discontinuation of oral anticoagulation therapy during most dental procedures because severe bleeding complications are rare and there is an increased risk for thromboembolic events in patients for whom warfarin therapy is interrupted. Although interruption of oral anticoagulation and bridge therapy with low-molecular- weight heparin (LMWH) may be indicated for high-risk individuals undergoing certain procedures, the use of LMWH in tooth extractions is expensive and often unnecessary. OBJECTIVE: The purpose of this review was to identify and characterize procedural use of LMWH for dental extractions with respect to current consensus recommendations. METHODS: The Idaho Medicaid pharmacy and medical claims database was queried to identify patients with a tooth extraction procedure between February 1, 1998, and January 31, 2005. Patients on warfarin therapy for 2 months before tooth extraction were identified as were claims for LMWH within 30 days before the procedure or 5 days after. Patient profiles were reviewed to determine number of extractions, rate of LMWH use, indication for anticoagulation, and associated drug costs. RESULTS: Of 55,260 Medicaid patients who had a tooth extraction, 518 (0.9%) had received warfarin for at least 2 consecutive months before the tooth extraction procedure. Of these, 31 patients (6%) received LMWH therapy at the time of extraction for a total of 35 procedures. All procedures selected for review carried a low bleeding risk, with an average of 1.3 teeth extracted per procedure. The indications for anticoagulation included 16 procedures (45.7%) involving patients with a history of a thromboembolic event more than 90 days before the procedure, 10 procedures (28.5%) involving patients with a prosthetic valve, 4 procedures (11.4%) involving anticoagulated patients with atrial fibrillation, and 5 procedures (14.2%) involving patients with a history of thromboembolism fewer than 3 months before the procedure. LMWH costs for these 35 extractions totaled $22,294, or an average of $637 per procedure or $474 per extracted tooth. Enoxaparin was used in all but 1 of the procedures, with an average 5-day supply (average 8 enoxaparin units) dispensed per procedure. The costs associated with the required additional drug monitoring, e.g., INR monitoring, were not included in this analysis. CONCLUSION: Although the overall number of dental procedures in anticoagulated patients using LMWH was small in our review, this inappropriate use resulted in avoidable costs to this Medicaid program. PMID- 17269838 TI - Medicare Part D: selected issues for pharmacists and beneficiaries in 2007. AB - BACKGROUND: Upon signing the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) on December 8, 2003, President Bush set in motion the greatest change in the Medicare program since its inception in 1965. MMA was implemented on January 1, 2006, and established the Medicare prescription drug benefit, also known as Medicare Part D. Community and managed care pharmacists were essential to the success in 2006 of this new benefit program with 33 million beneficiaries. Pharmacists will continue to be an essential and integral part of the continued success of the Medicare prescription drug benefit in 2007, in part by being informed about the policies and regulations. OBJECTIVE: To review policy statements released by the Centers for Medicare & Medicaid Services (CMS) for the Medicare prescription drug benefit in 2006 and to compile an abridged version of the highlights from the policy statements that may affect pharmacists and their interaction with Medicare beneficiaries. METHODS: We reviewed all policy statements that were released publicly via the CMS Web site (www.cms.gov) policy guidance section between January 1, 2006, and September 30, 2006. We read through approximately 100 guidance statements and summarized approximately 50 that were determined to be relevant to beneficiaries and pharmacists in various practice settings. RESULTS: Policy statements that may impact beneficiaries of the Medicare prescription drug benefit in 2007 include the timeline for the annual coordinated election period, managed care open enrollment period, and distribution of annual notices of change to beneficiaries. Changes have also occurred in the standard benefit and cost sharing for low-income subsidy (LIS) or extra help that some beneficiaries are eligible to receive based on their current financial status. Discontinuation of coverage of erectile dysfunction drugs is a noteworthy coverage change. For all health care providers, the National Provider Identification (NPI) number will be used beginning May 23, 2007. Once the system using NPI numbers is required, no other provider identification number will be valid for billing Medicare and Medicaid. CONCLUSION: Important policy updates to the Medicare prescription drug benefit in 2007 include the subject areas of: (1) beneficiary enrollment, (2) transition medication fills, (3) standard benefit, (4) cost sharing, particularly for those who qualify for LIS, (5) enhancement of the Medicare Prescription Drug Plan Finder, (6) beneficiary complaints, (7) discontinuation of coverage for erectile dysfunction drugs, (8) vaccine coverage by the Medicare prescription drug benefit, (9) syringes in long-term care, (10) donation of unused medications by beneficiaries, (11) implementation of the NPI, and (12) preventive services covered by the Medicare program. PMID- 17269839 TI - Bridging the gap between pharmacoeconomics and the real-world practice of managed care pharmacy. PMID- 17269840 TI - Medication therapy management versus drug regimen review. PMID- 17269841 TI - Peeking inside the statistical black box: how to analyze quantitative information and get it right the first time. PMID- 17269842 TI - Administrative claims analysis of the relationship between warfarin use and risk of hemorrhage including drug-drug and drug-disease interactions. AB - BACKGROUND: Despite the risk of hemorrhage, warfarin is the most commonly used oral anticoagulant today, both as monotherapy and when taken in combination with selected drugs. Warfarin is used most commonly for irregular heartbeat, after a heart attack, and after joint or heart valve replacement surgery. OBJECTIVE: To evaluate the relative risk of hemorrhage in health plan members who received warfarin concomitant with a drug known to cause an interaction or after diagnosis of liver disease or heart failure (HF). METHODS: A cohort study sample was drawn from an administrative database comprising medical and pharmacy claims for 1.7 million health plan members. A health plan member was defined as anyone who was eligible for pharmacy and medical benefits at any time from October 1, 2003, to September 30, 2004. To be included in the study, a member must have received at least 1 pharmacy claim for warfarin during the study period and been younger than 100 years. Hemorrhage was defined as a diagnosed bleeding episode recorded on a medical claim within 7 calendar days of a fill date for a pharmacy claim (new or refill) for warfarin. The following variables were used to predict the outcome measures: type of drug-drug or drug-disease interaction, patient age and gender, number of unique prescribers during the year for all drugs, specialty of the first prescriber for warfarin, average dose of warfarin, and days of warfarin therapy. Because individuals were followed only during the calendar year under study, the authors have interpreted the days of therapy measured primarily as a control on exposure. The outcome measures are prevalence of drug and disease interactions among members receiving warfarin therapy and the per-patient-per year and per-member-per-month (PMPM) cost of medical treatment of hemorrhage associated with warfarin therapy including drug and disease interactions. Costs are defined as the total paid amount for a procedure or service after negotiated provider discounts and subtraction of patient copay and deductibles. Logistic regression was used to evaluate the relative risk of hemorrhage in users of warfarin monotherapy and of warfarin users with drug-drug and drug-disease interactions. The comparison group in the logistic regression comprised the members who were not diagnosed with either HF or liver disease and who received warfarin therapy but none of the drugs under study known to cause drug interactions. Therefore, the odds ratios [ORs] produced were estimates of the relative risk of hemorrhage when taking warfarin concomitant with selected drugs and diseases. RESULTS: Of the 17,895 patients who used warfarin during the study year, 2,634 (14.7%) were diagnosed with a hemorrhage event within 1 week after filling a prescription for warfarin. The factors associated with an increased risk of hemorrhage included female gender (OR 1.149; 95% confidence interval [CI], 1.053- 1.253), liver disease (OR 1.764; 95% CI, 1.360-2.288), and HF (OR 1.559; 95% CI, 1.373-1.770). Compared with the use of warfarin alone, the use of either cephalosporins (OR 1.157; 95% CI, 1.043-1.285) or metronidazole (OR 1.578; 95% CI, 1.321-1.886) was associated with increased risk of hemorrhage, whereas the risk of hemorrhage was not greater for concomitant use of warfarin with amiodarone, fibric acid derivatives, or nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors. There was no relationship between estimated average daily warfarin dose and prevalence of hemorrhage. Other variables associated with an increased risk of hemorrhage were increased patient age, female gender, 120 days or more of warfarin therapy during the year, 2 or more unique prescriber numbers, and the medical specialty of the first prescriber of warfarin. Over the population of 1.7 million members, the cost for all hemorrhage events within 7 days of a pharmacy claim for warfarin was 0.40 dollars PMPM. CONCLUSIONS: Only 2 of 5 combinations of warfarin with drugs in this study were found to be associated with a higher prevalence of hemorrhage compared with warfarin use alone. The absolute prevalence of hemorrhage in users of warfarin and metronidazole was 22.7% and 17.2% for warfarin and cephalosporins, respectively, versus 14.2% in users of warfarin alone. The prevalence of hemorrhage for concomitant use of warfarin and NSAIDs/COX-2 inhibitors, amiodarone, or fibric acid derivatives such as fenofibrate was not greater than for warfarin alone. Liver disease or HF in warfarin users was associated with a significant increase in the likelihood of hemorrhage. PMID- 17269843 TI - Physician conformity and patient adherence to ACE inhibitors and ARBs in patients with diabetes, with and without renal disease and hypertension, in a medicaid managed care organization. AB - BACKGROUND: The American Diabetes Association (ADA) recommends using angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients with diabetes and comorbid hypertension or renal disease. OBJECTIVE: To examine the use of ACE inhibitors and ARBs in members of a Medicaid managed care organization (MCO) with diabetes and a diagnosis of hypertension and/or kidney disease to determine to what extent (1) physicians are conforming to the recommended course of treatment according to ADA guidelines published in 2002 and still current and (2) patients are adhering to their prescribed therapy. METHODS: Patients with diabetes were identified using medical claims from a Medicaid MCO in Maryland of approximately 118,000 members continuously enrolled during the study period. To be included in the cohort, members had to have at least 1 medical claim containing a diagnosis of diabetes mellitus from April 1, 2001, through March 31, 2002, using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 250.xx. Additional medical claims during the same time period for hypertension, ICD-9- CM code 401.xx, and renal disease, ICD-9-CM codes for nephropathy (582.81 or 582.9), proteinuria (791.0), or diabetic nephropathy (250.40 or 250.42 for type 2 diabetes only), were used to categorize the cohort into 4 subgroups: diabetes and renal disease with hypertension, diabetes and renal disease without hypertension, diabetes and hypertension without renal disease, and diabetes without renal disease and without hypertension. Pharmacy claims for ACE inhibitors and ARBs were obtained from July 1, 2001, through June 30, 2002, and utilization was defined as the patient having at least 1 pharmacy claim for an ACE inhibitor or an ARB. Patient adherence with ACE inhibitor or ARB therapy was measured using medication possession ratio (MPR) and median gap between prescription refills. RESULTS: There were 1,698 patients, approximately 2.3% of the total continuously enrolled members, with 1 or more medical claims containing an ICD-9-CM code of 250.xx for diabetes mellitus. The average age was 48 13.2 years for the total sample, and nearly 70% of the patients were women (1,188 women and 510 men). Only 13% of the patients in the sample had medical claim evidence of any renal involvement, while 63% of the study patients had hypertension. A total of 915 patients (53.9%) had at least 1 pharmacy claim for an ACE inhibitor or an ARB, accounting for 7,934 unique pharmacy claims, an average of 8.7 pharmacy claims per patient. Patients with renal involvement and without hypertension (47%) were less likely to receive an ACE inhibitor or an ARB than patients with renal involvement and hypertension (85%) (P <0.001). Patients without renal involvement or hypertension (19%) were less likely to receive an ACE inhibitor or an ARB than patients with hypertension and no renal involvement (71%) (P <0.001). The MPR for all patients was 0.77 ( 0.26). MPR and median gap did not differ significantly by sex. However, we found a significant correlation between age and MPR (P <0.001). In this sample with an age range of 18 to 65 years, there was a positive relationship between patient age and adherence to ACE inhibitor or ARB therapy. CONCLUSIONS: Physicians. conformity is high when they prescribe an ACE inhibitor or ARB for patients with diabetes and hypertension but is lower than expected for patients with diabetes and renal disease but without hypertension. Older patients in this analysis of persons aged 18 to 65 years adhered more to their ACE inhibitor or ARB therapy. PMID- 17269844 TI - Liver and thyroid monitoring in ambulatory patients prescribed amiodarone in 10 HMOs. AB - BACKGROUND: Amiodarone can cause liver and thyroid toxicity, but little is known about compliance with laboratory tests to evaluate liver and thyroid function among ambulatory patients who are dispensed amiodarone. OBJECTIVES: The primary objective of this study was to identify the proportion of ambulatory patients who had liver aminotransferase and thyroid function tests during amiodarone therapy. Secondary objectives were to (1) describe factors associated with receipt of laboratory tests and (2) determine the accuracy of administrative data for assessing aminotransferase and thyroid function monitoring. METHODS: This retrospective cohort study was conducted at 10 health maintenance organizations (HMOs) for the dates of service from January 1, 1999, through June 30, 2001. Participants included 1,055 patients dispensed amiodarone for at least 180 days within this date range; these patients were not necessarily new starts on amiodarone. Administrative claims data were analyzed to assess the percentage of patients with completed alanine/aspartate aminotransferase and thyroid function tests. Depending on the HMO site, electronic or paper medical records were reviewed to evaluate the validity of administrative claims data. Logistic regression models were used to explore factors associated with receipt of laboratory tests. RESULTS: Both aminotransferase and thyroid function tests were completed in 53.3% of patients within a 210-day follow-up period that included the 180-day period of amiodarone dispensings plus 30 days. Thyroid function, with or without liver function (aminotransferase tests), was assessed in 61.9% of patients, and aminotransferase tests, with or without thyroid function, were assessed in 68.2% of patients. After adjusting for patient characteristics and site, the factor most strongly associated with having both types of laboratory tests evaluated was concomitant therapy with a statin (adjusted odds ratio (OR) 1.55; 95% confidence interval (CI), 1.05-2.29). Other factors associated with having both types of laboratory tests evaluated included the number of outpatient visits in the 6 months before the period of amiodarone dispensings (adjusted OR 1.06; 95% CI, 1.00- 1.13 for each additional 5 visits) and living in a neighborhood where a higher median percentage of people had a high school or higher education (adjusted OR 1.09; 95% CI, 1.00-1.18 for every 10% increase in educational level at the block level). There was no association between monitoring and patient illness severity as measured by the number of comorbid conditions. On the basis of an evaluation of a randomly selected subset of 104 patient records, the sensitivity and specificity of automated data were 94.2% and 85.7% for aminotransferase tests and 83.3% and 81.1% for thyroid function tests, respectively. CONCLUSIONS: Approximately half of ambulatory patients dispensed amiodarone received both recommended laboratory tests for liver and thyroid function. Improved rates of testing for liver aminotransferase and thyroid function are needed for patients who receive amiodarone. PMID- 17269845 TI - Relationship of the use and costs of physician office visits and prescription drugs to travel distance and increases in member cost share. AB - BACKGROUND: The prescription drug benefit is commonly designed and managed as a stand-alone health insurance product without consideration of how the design of other medical benefits may impact its use. OBJECTIVE: To determine the effects of member cost (copayment/coinsurance) increases on the relationship between the use of physician office visits and the type/tier of prescription medication purchased in a commercially insured population. METHODS: Our research model utilized managed care organization member costshare levels that were changed as part of the annual benefit renewal process to estimate the price.quantity.expenditure relationship between cost sharing and use of physician office visits/prescription drugs by benefit tier. The price.quantity. expenditure relationship was measured across a benefit copayment price change to determine the effect of a price increase on utilization/expenditures. We included the distance from the member.s residence to the physician.s office as a proxy for the time cost of an office visit. The study sample included 44,828 members who were fully insured for the full 12 months of 2002, continued coverage for the full 12 months of 2003, and whose benefit renewal occurred on January 1, 2003. We hypothesize that a relationship exists between office visit use and its expenditures and prescription drug use and its expenditures based on out-of-pocket cost. Hypotheses were tested using a least squares dummy variable regression model across claims records for years 2002 and 2003, containing consecutive yearly records for the same members. The unit of analysis was the member. Demand was estimated by benefit category and copayment tier to provide the study variables, price elasticity of demand, cross-price elasticity of demand, and distance elasticity. Expenditure is net health plan cost after subtraction of member cost share (including copayments, coinsurance, and deductibles). The expenditure categories in this study were pharmacy, medical office visits, and total health care costs. RESULTS: Members with greater travel distance to a primary care physician (PCP) or specialty care physician (SCP) office experienced higher PCP and SCP visit utilization (distance elasticity = 0.164 and 0.202, respectively; P <0.01). Greater travel distance to a PCP was also associated with higher tier-1 prescription use (0.048, P <0.01) as well as higher total plan-paid (0.032, P <0.05) and PCP expenditures (0.141, P <0.01). Greater travel distance to an SCP was associated with higher use of drugs in all 3 pharmacy copayment tiers (0.085, 0.075, and 0.073 for tier 1, tier 2, and tier 3, respectively; P <0.01 for each tier). The price effects of an increase in tier-1 copayments were fewer PCP office visits (-0.118, P <0.01) but more SCP office visits (0.177, P <0.01); SCP visits were also higher with increased tier-3 copayments (0.118, P <0.01). Tier-2 prescription drug use decreased with higher office visit copayments (-0.105, P <0.05). Increased tier-1 copayments were associated with lower expenditures for PCP office visits (-0.146, P <0.05) but higher expenditures for SCP office visits (0.149, P <0.05). While increases in tier-2 copayments were associated with lower PCP (and -0.322, P <0.01) and SCP (-0.453, P <0.01) expenditures, increases in tier-3 copayments were associated with higher PCP (0.495, P <0.01) and SCP (0.197, P <0.05) expenditures. CONCLUSIONS: A relationship exists between physician office visits and prescription drug use based on member cost share and time factors. Increases in office visit copayments were associated with decreased use of drugs in the tier-2 pharmacy benefit category. Increases in tier-2 pharmacy benefit copayment levels were associated with lower PCP/SCP expenditures, but increases in tier-3 pharmacy benefit copayment levels were associated with higher PCP/SCP expenditures. The distance to a physician.s office was directly proportional to the number of office visits. Separation of the management of pharmacy and medical benefits may have significant cost implications for consumers, employers, and health plans. Therefore, optimal management of medical and pharmacy benefits may require a coordinated strategy and tactics. PMID- 17269846 TI - Prevalence of drug-related problems and cost-savings opportunities in medicaid high utilizers identified by a pharmacist-run drug regimen review center. AB - BACKGROUND: Despite numerous reports of state Medicaid drug utilization review (DUR) programs, little data are available about the prevalence of drugrelated problems (DRPs) in Medicaid patients. A university-based, pharmacist-run DUR program for high utilizers was created as an alternative to imposition of a statutory limit of 7 medications per month in the Utah Medicaid program in 2002. The DUR program was designed to suggest ways that high-utilizing patients could decrease their total number of medications to 7 or fewer prior to imposition of the 7-medication limit at some time in the future. OBJECTIVE: To describe the experience in 1 Medicaid DUR program and to report the prevalence of DRPs and cost-saving opportunities (CSOs) among a population of Medicaid recipients who were high utilizers of prescription drugs. METHODS: DRPs were identified by 5 clinical pharmacists employed by the Drug Regimen Review Center (DRRC) in Salt Lake City. The purpose of the center was to provide drug therapy review services for a select number of Utah Medicaid recipients (200-300 per month) who exceeded a 7-medication limit during the calendar years 2003 and 2004. RESULTS: Out of 391,890 eligible Medicaid recipients, 242,411 (62%) received at least 1 medication, and 16,958 (4.3%) exceeded the 7-medication limit during the review period. Of those exceeding the limit, the DRRC reviewed a total of 3,706 (21.9%) patients, representing the highest utilizers by volume of medication. The prevalence of DRPs considered clinically important in the review cohort was 79.7% of patients, including therapeutic duplications in 54.6% of patients, dose form optimization in 29.7%, and inappropriate uncoordinated care in 25.3%. The average pharmacy cost per month for patients with at least 1 DRP was 1,081 dollars; by contrast, the average pharmacy cost per month for all other patients receiving at least 1 prescription was 91 dollars. CONCLUSIONS: Approximately 4% of Medicaid recipients exceeded the 7-medication monthly limit. Among the 22% highest utilizers in this group, 48% of nursing home residents and 87% of ambulatory recipients had at least 1 DRP, or an overall rate of 80% of high-use Medicaid recipients or as much as 3.2% of the Medicaid population. PMID- 17269847 TI - False-positive versus true-positive drug-drug interactions with warfarin. PMID- 17269848 TI - Rhythm versus safety in amiodarone therapy. PMID- 17269849 TI - What evidence supports guidelines for use of ACE inhibitors and ARBs in diabetes? PMID- 17269852 TI - Postmenopausal osteoporosis: etiology, current diagnostic strategies, and nonprescription interventions. AB - OBJECTIVE: To describe the etiology, diagnosis, and nonprescription interventions for the prevention and treatment of postmenopausal osteoporosis. BACKGROUND: Osteoporosis affects more than 20 million individuals in North America and is responsible for more than 1.5 million fractures in the United States. About 50% of white women in the United States will have an osteoporotic fracture during their lifetime. SUMMARY: Postmenopausal osteoporosis is the result of estrogen deficiency, which results in up-regulation of several cytokines and excessive bone resorption. Various bone mineral density (BMD) testing methods are available, but the World Health Organization based the diagnosis of postmenopausal osteoporosis on the presence of a BMD T-score that is 2.5 standard deviations or greater below the mean for young women as assessed by dual-energy X ray absorptiometry (DXA) at the hip, spine, and mid-radius. Ensuring adequate calcium and vitamin D intake is the cornerstone of any regimen aimed at preventing or treating postmenopausal osteoporosis. Other nonpharmacologic measures address modifiable risk factors for the disease and include exercise, smoking cessation, reducing consumption of caffeine and alcohol, and avoiding medications known to decrease bone mass. CONCLUSIONS: Postmenopausal osteoporosis is the result of estrogen deficiency and excessive bone resorption. Ensuring intake combined with lifestyle changes to address modifiable risk factors for the disease may help in the prevention and treatment of this condition. PMID- 17269850 TI - Prevalence of phosphodiesterase-5 inhibitor use in the VHA in 2004 and 2005 is twice that of a commercial health plan in 2001. PMID- 17269854 TI - Medication adherence: a challenge for patients with postmenopausal osteoporosis and other chronic illnesses. AB - OBJECTIVE: To define medication adherence and describe the limitations of various assessment methods, reasons for nonadherence to medications used to manage chronic illness, the impact of nonadherence to osteoporosis medications, and strategies for improving medication adherence. BACKGROUND: Medication nonadherence is a major public health problem that adversely affects patient outcomes and increases health care utilization and costs. Postmenopausal osteoporosis is a chronic disease, and adherence to drug therapy used to manage the disease is as much of a challenge as it is in other chronic diseases. SUMMARY: Medication adherence reflects both compliance and persistence. Direct assessment methods (e.g., observation, laboratory serum drug assays) are more accurate than indirect methods, but they are more costly and often impractical. Indirect methods include patient self-report and the use of prescription refill records, pill counts, and electronic monitoring devices. Medication adherence in patients with postmenopausal osteoporosis or other chronic illnesses is less than optimal. Adverse effects, financial constraints, mis-communication with the prescriber, and a perception that medications are unnecessary are among the possible reasons for medication nonadherence. Unintentional nonadherence is a passive process, often simply forgetting, and intentional nonadherence is an active process involving a deliberate choice, often based on adverse effects or a perceived lack of benefit. CONCLUSIONS: Nonadherence to osteoporosis medications can adversely affect patient outcomes and increase health care utilization and costs. An individualized approach to improving medication adherence based on patient preferences and readiness to change is needed. PMID- 17269853 TI - Prescription drug therapies for prevention and treatment of postmenopausal osteoporosis. AB - OBJECTIVE: To characterize the changes in bone mass with age in women and men, explain the physiology and pathophysiology of the bone remodeling process, identify the targets for prescription osteoporosis drugs in this process, and provide details about the uses, efficacy, safety, and economics of prescription drug therapies for osteoporosis prevention and treatment. BACKGROUND: Preventing accelerated bone loss and decreasing age-related decreases in bone density are the primary goals of prescription drug therapy for osteoporosis. Bisphosphonates are the drugs of choice for preventing and treating postmenopausal osteoporosis. Alternatives for patients who cannot take bisphosphonates include raloxifene and calcitonin salmon. SUMMARY: Menopause is accompanied by a rapid loss in bone mass that is followed by annual losses due to aging in women, which are similar to age related bone mass decreases in men. Most prescription drug therapies for osteoporosis prevention or treatment reduce bone resorption by inhibiting osteoclast activation and activity, with only one medication class able to increase bone formation by stimulating osteoblasts. Denosumab, an investigational monoclonal antibody that inhibits nuclear factor kB ligand, would be a new class of anti-resorptive medications. Bisphosphonates currently are the drugs of choice for preventing and treating osteoporosis, with 7- and 10-year safety data available for risedronate and alendronate, respectively. Weekly and monthly regimens of bisphosphonates improve patient acceptance. Recently, an injectable form of ibandronate received U.S. Food and Drug Administration approval for once every 3 months administration. Raloxifene and calcitonin salmon are alternatives for patients who cannot take bisphosphonates because of contraindications or adverse effects. Teriparatide, a recombinant parathyroid hormone fragment, not only increases bone mineral density but also increases bone connectivity. CONCLUSIONS: Osteoporosis medications are usually safe, especially if used correctly with proper patient education. Treating osteopenia has not been found to be cost effective in women. However, obtaining a dual-energy X-ray absorptiometry scan and treating osteoporosis has resulted in cost savings in senior women living in community and nursing home residences. Pharmacists have multiple opportunities for preventing and treating osteoporosis. PMID- 17269855 TI - Skill shortages in health: innovative solutions using vocational education and training. AB - INTRODUCTION: This article reports findings of a project funded by the Australian National Council for Vocational Education Research. The project explores solutions to current and projected skills shortages within the health and community services sector, from a vocational education and training perspective. Its purpose is to locate, analyse and disseminate information about innovative models of health training and service delivery that have been developed in response to skill shortages. METHODS: The article begins with a brief overview of Australian statistics and literature on the structure of the national health workforce and perceived skill shortages. The impact of location (state and rurality), demographics of the workforce, and other relevant factors, on health skill shortages is examined. Drawing on a synthesis of the Australian and international literature on innovative and effective models for addressing health skill shortages and nominations by key stakeholders within the health sector, over 70 models were identified. The models represent a mixture of innovative service delivery models and training solutions from Australia, as well as international examples that could be transposed to the Australian context. They include the skill ecosystem approach facilitated by the Australian National Training Authority Skill Ecosystem Project. Models were selected to represent diversity in terms of the nature of skill shortage addressed, barriers overcome in development of the model, healthcare specialisations, and different customer groups. RESULTS: Key barriers to the development of innovative solutions to skills shortages identified were: policy that is not sufficiently flexible to accommodate changing workplace needs; unwillingness to risk take in order to develop new models; delays in gaining endorsement/accreditation; current vocational education and training (VET) monitoring and reporting systems; issues related to working in partnership, including different cultures, ways of operating, priorities and timelines; workplace culture that is resistant to change; and organisational boundaries. For training-only models, additional barriers were: technology; low educational levels of trainees; lack of health professionals to provide training and/or supervision; and cost of training. Key enhancers for the development of models were identified as: commitment by all partners and co-location of partners; or effective communication channels. Key enhancers for model effectiveness were: first considering work tasks, competencies and job (re)design; high profile of the model within the community; community-based models; cultural fit; and evidence of direct link between skills development and employment, for example VET trained aged care workers upskilling for other health jobs. For training only models, additional enhancers were flexibility of partners in accommodating needs of trainees; low training costs; experienced clinical supervisors; and the provision of professional development to trainers. CONCLUSIONS: There needs to be a balance between short-term solutions to current skill shortages (training only), and medium to longer term solutions (job redesign, holistic approaches) that also address projected skills shortages. Models that focus on addressing skills shortages in aged care can provide a broad pathway to careers in health. Characteristics of models likely to be effective in addressing skill shortages are: responsibility for addressing skills shortage is shared between the health sector, education and training organisations and government, with employers taking a proactive role; the training component is complemented by a focus on retention of workers; models are either targeted at existing employees or identify a target group(s) who may not otherwise have considered a career in health. PMID- 17269856 TI - Human amniotic membrane as a delivery matrix for articular cartilage repair. AB - The purpose of this study is to evaluate the feasibility of human amniotic membrane (HAM) as a chondrocyte carrier by assessing cell proliferation and maintenance of phenotype in vitro and cartilage regeneration in vivo. Intact HAM was treated with 0.1% trypsin-ethylenediaminetetraacetic acid (EDTA) for 15 min and the epithelial cells removed to make a denuded HAM. Rabbit articular chondrocytes were then seeded on three different HAM substrates: the epithelial side of intact HAM (IHE), basement side of denuded HAM (DHB), and stromal side of denuded HAM (DHS). These cell-substrate specimens were cultured for up to 4 weeks, and cell proliferation rate and phenotypic stability were examined at weeks 1 and 4. While chondrocytes grew in monolayer fashion on the surface of IHE and DHB substrates, the cells seeded in DHS penetrated and spread into the whole thickness of the stromal layer. The proliferating activity of chondrocytes in DHB was continuously up-regulated. A similar proliferating activity was observed in DHS in the first week, which remained stable for up to 4 weeks. The expression of type II collagen gradually increased with time in the DHS group, while it gradually decreased in the DHB group or was not detected at all in the IHE group. These results suggested that denuded HAM was able to support chondrocyte proliferation and maintenance of phenotype in vitro, seemingly more favorable when DHS was used. Based on this data, the DHS with chondrocytes was used to cover rabbit osteochondral defect with the stromal side facing in. The defect area was successfully regenerated with hyaline cartilage in the Safranin-O stain and International Cartilage Repair Society (ICRS) scoring after 8 weeks of implantation. In conclusion, our findings suggest that denuded HAM could be one of the ideal cell carrier matrices for cartilage regeneration. PMID- 17269860 TI - Questions comparison of biopsy procedures in cats. PMID- 17269861 TI - The need for a food supply-exclusive college of veterinary medicine. PMID- 17269862 TI - What is your diagnosis? A bismuth subsalicylate tablet in the stomach. PMID- 17269863 TI - What is your diagnosis? A metallic foreign body in the dorsal aspect of the pharyngeal recess. PMID- 17269864 TI - Veterinary legal issues: 2006 in review. PMID- 17269865 TI - Evaluation of short-term limb function following unilateral carbon dioxide laser or scalpel onychectomy in cats. AB - OBJECTIVE: To evaluate short-term postoperative forelimb function after scalpel and laser onychectomy in cats. DESIGN: Randomized, prospective study. ANIMALS: 20 healthy adult cats. PROCEDURES: Cats were randomly assigned to the laser (n = 10) or scalpel (10) onychectomy group. Unilateral left forelimb onychectomy was performed. In the scalpel group, a tourniquet was used during surgery and a bandage was applied after surgery. Pressure platform gait analysis was performed prior to and 1, 2, 3, and 12 days after onychectomy. Peak vertical force (PVF), vertical impulse, and the ratio of the PVF of the left forelimb to the sum of the remaining limbs (PVF ratio) were used as outcome measures. RESULTS: The laser onychectomy group had significantly higher ground reaction forces on days 1 and 2 and significantly higher PVF ratio on day 12, compared with the scalpel group. Similarly, significant differences were found in change in ground reaction forces on days 1 and 2 and the PVF ratio on day 12, compared with day -1. No cats required rescue analgesia during the course of the study. One cat in the laser group had signs of depression and was reluctant to walk on day 2 after surgery, had physical examination findings consistent with cardiac insufficiency, and was euthanized. CONCLUSIONS AND CLINICAL RELEVANCE: Cats had improved limb function immediately after unilateral laser onychectomy, compared with onychectomy with a scalpel, tourniquet, and bandage. This improved limb function may result from decreased pain during the 48 hours following unilateral laser onychectomy. PMID- 17269866 TI - Effect of vaccination on parvovirus antigen testing in kittens. AB - OBJECTIVE: To determine the frequency and duration of feline panleukopenia virus (FPV) vaccine-induced interference with fecal parvovirus diagnostic testing in cats. DESIGN: Prospective controlled study. ANIMALS: Sixty-four 8- to 10-week-old specific-pathogen-free kittens. PROCEDURES: Kittens were inoculated once with 1 of 8 commercial multivalent vaccines containing modified-live virus (MLV) or inactivated FPV by the SC or intranasal routes. Feces were tested for parvovirus antigen immediately prior to vaccination, then daily for 14 days with 3 tests designed for detection of canine parvovirus. Serum anti-FPV antibody titers were determined by use of hemagglutination inhibition prior to vaccination and 14 days later. RESULTS: All fecal parvovirus test results were negative prior to vaccination. After vaccination, 1 kitten had positive test results with test 1, 4 kittens had positive results with test 2, and 13 kittens had positive results with test 3. Only 1 kitten had positive results with all 3 tests, and only 2 of those tests were subjectively considered to have strongly positive results. At 14 days after vaccination, 31% of kittens receiving inactivated vaccines had protective FPV titers, whereas 85% of kittens receiving MLV vaccines had protective titers. CONCLUSIONS AND CLINICAL RELEVANCE: Animal shelter veterinarians should select fecal tests for parvovirus detection that have high sensitivity for FPV and low frequency of vaccine-related test interference. Positive parvovirus test results should be interpreted in light of clinical signs, vaccination history, and results of confirmatory testing. Despite the possibility of test interference, the benefit provided by universal MLV FPV vaccination of cats in high-risk environments such as shelters outweighs the impact on diagnostic test accuracy. PMID- 17269867 TI - Evaluation of the reproducibility and accuracy of pH-determining devices used to measure urine pH in dogs. AB - OBJECTIVE: To evaluate the reproducibility and accuracy of 4 portable pH meters, a reagent strip, and pH paper for measuring urine pH in dogs. DESIGN: Prospective masked randomized study. SAMPLE POPULATION: 201 free-catch urine samples from 114 hospitalized dogs. PROCEDURES: Urine samples were divided into 2-mL aliquots. Measurements of urine pH were obtained by use of a laboratory benchtop pH meter, 4 portable pH meters, a urine reagent strip, and pH paper. The pH of each aliquot was measured within 4 hours of collection by an evaluator unaware of the aliquot's origin. To assess reproducibility, the coefficient of variation for each pH measurement device was calculated. To determine which device was most accurate, the degree of agreement among the different devices was assessed in comparison with the benchtop pH meter, which was considered the reference method. RESULTS: 3 of the 4 portable pH meters had nearly perfect agreement with the reference method. The reagent strip and pH paper had moderate to poor agreement with the reference method. CONCLUSIONS AND CLINICAL RELEVANCE: Urine pH measurements should be made by use of a portable or benchtop pH meter when accurate measurements are crucial for diagnosis or treatment. Reagent strips and pH papers are useful in obtaining pH approximations but are not recommended when accurate measurements of urine pH are required. PMID- 17269868 TI - Treatment of traumatic cervical myelopathy with surgery, prolonged positive pressure ventilation, and physical therapy in a dog. AB - CASE DESCRIPTION: A 9-year-old dog was evaluated for traumatic cervical myelopathy after a surgical attempt to realign and stabilize the C2 and C3 vertebrae. CLINICAL FINDINGS: The dog could not ventilate spontaneously and was tetraplegic; positive-pressure ventilation (PPV) was maintained. Myelography and computed tomography revealed spinal cord compression with subluxation of the C2 and C3 vertebrae and extrusion of the C2-3 intervertebral disk. TREATMENT AND OUTCOME: Surgically, the protruding disk material was removed and the vertebrae were realigned with screws and wire. For PPV, assist control ventilation in volume control mode and then in pressure control mode was used in the first 6 days; this was followed by synchronized intermittent mandatory ventilation until 33 days after the injury; then only continuous positive airway pressure was provided until the dog could breathe unassisted, 37 days after the injury. Physical therapy that included passive range of motion exercises, neuromuscular electrical stimulation, and functional weight-bearing positions was administered until the dog was discharged 46 days after injury; the dog was severely ataxic and tetraparetic but could walk. Therapy was continued at home, and 1 year later, the dog could run and had moderate ataxia and tetraparesis. CLINICAL RELEVANCE: Hypoventilation with tetraparesis in traumatic spinal cord injury can be successfully treated with PPV exceeding 30 days, surgery, and physical therapy. PMID- 17269869 TI - Subtotal penile amputation and preputial urethrostomy in a dog. AB - CASE DESCRIPTION: A 6-year-old castrated male Shih Tzu was evaluated because of intermittent bleeding during urination. CLINICAL FINDINGS: Necrosis of the cranial portion of the penile shaft extended distally from the preputial fornix. Penile necrosis secondary to strangulation from paraphimosis was diagnosed. TREATMENT AND OUTCOME: A midline preputiotomy incision was used to expose the penile shaft; amputation was performed caudal to the preputial fornix. The terminal portion of the urethra was anastomosed to the preputial mucosa, which allowed the dog to urinate through the preputial orifice. CLINICAL RELEVANCE: Unlike the more conventional urethrostomy procedures performed in dogs, preputial urethrostomy eliminates the potential for local skin irritation during urination. Preputial urethrostomy is also easier to perform in those dogs in which penile amputation is required adjacent to the preputial fornix. A release incision cranial to the prepuce can be used to facilitate caudal displacement of the preputial mucosa, which facilitates urethral anastomosis to this structure. A midline preputiotomy incision provided excellent exposure of the penile shaft for this surgical procedure. PMID- 17269870 TI - Ultrasound-assisted collection of cerebrospinal fluid from the lumbosacral space in equids. AB - OBJECTIVE: To describe ultrasonographic landmarks for use in collection of CSF from the lumbosacral region in equids. DESIGN: Prospective study. ANIMALS: 37 equids (27 with neurologic disease and 10 with nonneurologic disease). PROCEDURES: Standing equids (n = 17) were sedated with detomidine hydrochloride (0.006 to 0.01 mg/kg [0.003 to 0.005 mg/lb], IV) followed by butorphanol tartrate (0.01 mg/kg, IV) and restrained with a nose twitch for collection of CSF. The CSF was collected from 20 laterally recumbent equids (10 sedated and 10 immediately after euthanasia). Anatomic landmarks were identified ultrasonographically. Height at the dorsal point of the shoulders, body weight, depth of the spinal needle, number of attempts to collect CSF, and cytologic evaluation of CSF were recorded. RESULTS: Lumbosacral puncture cranial to the cranial border of the most superficial location of both tuber sacrale along the midline was consistently successful for CSF collection (35/37 equids). Two horses had anatomic abnormalities that precluded CSF collection. Mean number of attempts to collect CSF per animal was 1.1. Height and body weight were strongly correlated with needle depth for CSF collection. Pelvic and sacral displacement was observed in several laterally recumbent animals, which resulted in discrepancies of the midline between the cranial and caudal aspects of the vertebral column. In most equids, the spinal needle was aligned on the midline of the caudal aspect of the vertebral column. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonography was a useful aid for collection of CSF from the lumbosacral space and decreased the risk of repeated trauma and contamination in equids. PMID- 17269872 TI - Human-directed aggression in miniature pet pigs. AB - OBJECTIVES: To determine whether associations exist between human-directed aggression and sex, neutering status, age of weaning, the presence of other pet pigs, or the presence of environmental enrichment objects in miniature pet pigs. DESIGN: Internet survey. STUDY POPULATION: Responses from 222 owners of miniature pet pigs. PROCEDURES: Pet pig owners were requested to complete a 48-item multiple-choice and short-answer Internet survey for each pig that they presently owned. RESULTS: Among 222 surveys that met enrollment criteria, human-directed aggression that occurred on at least 1 occasion was reported in 64% (n = 142) and aggression that occurred once or more per month was reported in 31% (69). No significant differences were found in the prevalence of human-directed aggression among castrated males, sexually intact females, and spayed females. Ages of weaning and neutering and the presence of objects intended to serve as environmental enrichment were not associated with frequency of aggression. A significant inverse association was detected between presence of other pigs in the same household and human-directed aggression, such that 21% (20/95) of pigs that lived with at least 1 conspecific were aggressive on a frequent basis, compared with 39% (49/126) of pigs that lived with no conspecific. A similar inverse association was evident regarding aggression that occurred on at least 1 occasion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that human directed aggression is a common problem in miniature pet pigs. The presence of a conspecific can be expected to reduce the likelihood of human-directed aggression. PMID- 17269873 TI - Naive averaged, naive pooled, and population pharmacokinetics of orally administered marbofloxacin in juvenile harbor seals. AB - OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after oral administration in juvenile harbor seals (Phoca vitulina) at a dose of 5 mg/kg (2.3 mg/lb) and to compare pharmacokinetic variables after pharmacokinetic analysis by naive averaged, naive pooled, and nonlinear mixed-effects modeling. DESIGN: Original study. Animals-33 male and 22 female juvenile seals being treated for various conditions. PROCEDURES: Blood collection was limited to < or = 3 samples/seal. Plasma marbofloxacin concentrations were measured via high pressure liquid chromatography with UV detection. RESULTS: Mean +/- SE dose of marbofloxacin administered was 5.3 +/- 0.1 mg/kg (2.4 +/- 0.05 mg/lb). The terminal half-life, volume of distribution (per bioavailability), and clearance (per bioavailability) were approximately 5 hours, approximately 1.4 L/kg, and approximately 3 mL/min/kg, respectively (values varied slightly with the method of calculation). Maximum plasma concentration and area under the plasma-time concentration curve were approximately 3 microg/mL and 30 h x microg/mL, respectively. Naive averaged and naive pooled analysis appeared to yield a better fit to the population, but nonlinear mixed-effects modeling yielded a better fit for individual seals. CONCLUSIONS AND CLINICAL RELEVANCE: Values of pharmacokinetic variables were similar regardless of the analytic method used. Pharmacokinetic variability can be assessed with nonlinear mixed-effects modeling, but not with naive averaged or naive pooled analysis. Visual observation by experienced trainers revealed no adverse effects in treated seals. Plasma concentrations attained with a dosage of 5 mg/kg every 24 hours would be expected to be efficacious for treatment of infections caused by susceptible bacteria (excluding Pseudomonas aeruginosa). PMID- 17269875 TI - Evaluation of cardiovascular effects of total intravenous anesthesia with propofol or a combination of ketamine-medetomidine-propofol in horses. AB - OBJECTIVE: To evaluate the cardiovascular effects of total IV anesthesia with propofol (P-TIVA) or ketamine-medetomidine-propofol (KMP-TIVA) in horses. ANIMALS: 5 Thoroughbreds. PROCEDURES: Horses were anesthetized twice for 4 hours, once with P-TIVA and once with KMP-TIVA. Horses were medicated with medetomidine (0.005 mg/kg, IV) and anesthetized with ketamine (2.5 mg/kg, IV) and midazolam (0.04 mg/kg, IV). After receiving a loading dose of propofol (0.5 mg/kg, IV), anesthesia was maintained with a constant rate infusion of propofol (0.22 mg/kg/min) for P-TIVA or with a constant rate infusion of propofol (0.14 mg/kg/min), ketamine (1 mg/kg/h), and medetomidine (0.00125 mg/kg/h) for KMP TIVA. Ventilation was artificially controlled throughout anesthesia. Cardiovascular measurements were determined before medication and every 30 minutes during anesthesia, and recovery from anesthesia was scored. RESULTS: Cardiovascular function was maintained within acceptable limits during P-TIVA and KMP-TIVA. Heart rate ranged from 30 to 40 beats/min, and mean arterial blood pressure was > 90 mm Hg in all horses during anesthesia. Heart rate was lower in horses anesthetized with KMP-TIVA, compared with P-TIVA. Cardiac index decreased significantly, reaching minimum values (65% of baseline values) at 90 minutes during KMP-TIVA, whereas cardiac index was maintained between 80% and 90% of baseline values during P-TIVA. Stroke volume and systemic vascular resistance were similarly maintained during both methods of anesthesia. With P-TIVA, some spontaneous limb movements occurred, whereas with KMP-TIVA, no movements were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Cardiovascular measurements remained within acceptable values in artificially ventilated horses during P-TIVA or KMP-TIVA. Decreased cardiac output associated with KMP-TIVA was primarily the result of decreases in heart rate. PMID- 17269876 TI - Effects of continuous oral administration of phenylbutazone on biomarkers of cartilage and bone metabolism in horses. AB - OBJECTIVE: To evaluate the effects of continuous oral administration of phenylbutazone on serum and synovial fluid biomarkers of skeletal matrix metabolism in horses. ANIMALS: 11 adult female horses without clinical or radiographic evidence of joint disease. PROCEDURES: Horses were randomly assigned to control or treatment groups. Phenylbutazone was administered orally twice daily at a dose of 4.4 mg/kg for 3 days to the treatment group and subsequently at a dose of 2.2 mg/kg for 7 days. Serum and radiocarpal synovial fluid samples were obtained at baseline and thereafter at regular intervals for 4 weeks. Biomarkers of cartilage aggrecan synthesis (chondroitin sulfate 846) and type II collagen synthesis (procollagen type II C-propeptide) and degradation (collagen type II cleavage) were assayed. Biomarkers of bone synthesis (osteocalcin) and resorption (C-terminal telopeptide of type I collagen) were also measured. RESULTS: No significant differences were found between control and treatment groups or temporally for the biomarkers chondroitin sulfate 846, procollagen type II C-propeptide, collagen type II cleavage, and C-terminal telopeptide of type I collagen in serum or synovial fluid. A significant increase in osteocalcin concentration occurred in synovial fluid during treatment in the treated group. No treatment effect was detected for serum osteocalcin concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that continuous phenylbutazone administration at recommended doses altered some biomarkers in healthy equine joints after short periods of administration. Increased osteocalcin concentration may indicate an undetermined anabolic effect of phenylbutazone administration on periarticular bone or transient induction of osteogenesis in articular chondrocytes or a mesenchymal subpopulation of synoviocytes. PMID- 17269877 TI - Effect of exercise on serum concentration of cartilage oligomeric matrix protein in Thoroughbreds. AB - OBJECTIVE: To evaluate changes in serum cartilage oligomeric matrix protein (COMP) concentrations in response to exercise in horses. ANIMALS: 15 horses in experiment 1 and 27 horses in experiment 2. PROCEDURES: In experiment 1, 15 Thoroughbreds free of orthopedic disease underwent a standardized exercise protocol. Running velocity and heart rate (HR) were recorded, and blood samples were collected immediately before (baseline) and 1, 5, and 24 hours after a single episode of exercise. In experiment 2, 27 horses underwent 9 stages of a training program in which each stage consisted of 4 to 8 consecutive daily workouts followed by a rest day. Blood samples were collected immediately before the first and final daily workouts in each stage. Serum COMP concentrations were measured via inhibition ELISA with a monoclonal antibody (14G4) against equine COMP. RESULTS: In experiment 1, mean serum COMP concentration was significantly higher than baseline 1 and 5 hours after exercise and returned to baseline concentrations 24 hours after exercise. Mean serum baseline COMP concentration increased as the velocity of running at maximum HR and at an HR of 200 beats/min increased, being significantly higher during the third and fourth exercise tests than during the first. In experiment 2, mean baseline COMP concentration at the final workout of each stage was significantly higher than that at the first workout, beginning with stage 3. CONCLUSIONS AND CLINICAL RELEVANCE: Serum COMP concentrations changed significantly in response to exercise. Exercise may enhance movement of COMP into the circulation as well as change the basal turnover rate of COMP. PMID- 17269878 TI - Comparison of noninvasive cardiac output measured by use of partial carbon dioxide rebreathing or the lithium dilution method in anesthetized foals. AB - OBJECTIVE: To compare cardiac output (CO) measured by use of the partial carbon dioxide rebreathing method (NICO) or lithium dilution method (LiDCO) in anesthetized foals. SAMPLE POPULATION: Data reported in 2 other studies for 18 neonatal foals that weighed 32 to 61 kg. PROCEDURES: Foals were anesthetized and instrumented to measure direct blood pressure, heart rate, arterial blood gases, end-tidal isoflurane and carbon dioxide concentrations, and CO. Various COs were achieved by administration of dobutamine, norepinephrine, vasopressin, phenylephrine, and isoflurane to allow comparisons between LiDCO and NICO methods. Measurements were obtained in duplicate or triplicate. We allowed 2 minutes between measurements for LiDCO and 3 minutes for NICO after achieving a stable hemodynamic plane for at least 10 to 15 minutes at each CO. RESULTS: 217 comparisons were made. Correlation (r = 0.77) was good between the 2 methods for all determinations. Mean +/- SD measurements of cardiac index for all comparisons with the LiDCO and NICO methods were 138 +/- 62 mL/kg/min (range, 40 to 381 mL/kg/min) and 154 +/- 55 mL/kg/min (range, 54 to 358 mL/kg/min), respectively. Mean difference (bias) between LiDCO and NICO measurements was -17.3 mL/kg/min with a precision (1.96 x SD) of 114 mL/kg/min (range, -131.3 to 96.7). Mean of the differences of LiDCO and NICO measurements was 4.37 + (0.87 x NICO value). CONCLUSIONS AND CLINICAL RELEVANCE: The NICO method is a viable, noninvasive method for determination of CO in neonatal foals with normal respiratory function. It compares well with the more invasive LiDCO method. PMID- 17269879 TI - Cardiac evaluation of anesthetized Grevy's zebras (Equus grevyi). AB - OBJECTIVE: To determine ECG and echocardiographic measurements in healthy anesthetized Grevy's zebras (Equus grevyi). ANIMALS: 20 healthy zebras. PROCEDURES: Auscultation, base-apex ECG, and echocardiography were performed on anesthetized zebras. RESULTS: Low-grade systolic murmurs were detected in the left basilar region in 4 of 20 zebras. Evaluation of ECGs from 19 zebras revealed sinus rhythm with a predominantly negative QRS complex and a mean +/- SD heart rate of 67 +/- 10 beats/min. Echocardiograms of sufficient image quality were obtained for 16 zebras. Interventricular septal thickness in diastole, left ventricular chamber in diastole and systole, left atrial diameter, and left ventricular mass were significantly and moderately correlated with estimated body weight (r values ranged from 0.650 to 0.884). Detectable swirling of blood in the right and sometimes the left ventricles was detected in 9 of 16 zebras, whereas physiologic regurgitation of blood was detected for the aortic valve in 3 zebras, pulmonary valve in 2 zebras, mitral valve in 2 zebras, and tricuspid valve in 1 zebra. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study provide reference information for use in the cardiac evaluation of anesthetized Grevy's zebras. PMID- 17269880 TI - Transcutaneous ultrasonographic evaluation of gastric distension with fluid in horses. AB - OBJECTIVE: To develop a transcutaneous ultrasonography (TUS) method for measuring the location of the stomach during various levels of fluid distension and evaluate any correlation between gastric fluid distension and stomach position. ANIMALS: 6 adult horses. PROCEDURES: Known volumes of water were administered in 2 trials. In trial 1, the stomach was evaluated prior to and after the administration of 2, 4, and 6 L of water. In trial 2, the stomach was evaluated after administration of 6, 8, 10, and 12 L of water. The TUS was performed at the 7th through 16th left intercostal spaces (ICSs). For each volume of water, an image was captured at the most dorsal point in each ICS where the dorsolateral aspect of the stomach wall was viewed. The distance between this point and a horizontal line drawn on the skin at the level of the elbow joint was measured. The measurements at all ICSs were used to estimate the gastric wall height at ICS 12, which was subsequently evaluated for statistical association with volume administered. RESULTS: Significant correlation between the estimated height of the stomach wall at ICS 12 and the volume of fluid administered was detected. A regression equation to estimate gastric fluid volume when initial values for gastric wall height (cm) at ICS 12 and fluid volume (L) are known was developed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that use of TUS for gastric fluid volume estimation is a potentially useful technique. PMID- 17269882 TI - Immunohistochemical evaluation of cyclooxygenase expression in corneal squamous cell carcinoma in horses. AB - OBJECTIVE: To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the cornea, eyelid, and third eyelid of healthy horses and those affected with squamous cell carcinoma (SCC) by use of immunohistochemical techniques. ANIMALS: 15 horses with SCC involving ocular tissues and 5 unaffected control horses. PROCEDURES: SCC-affected tissues were obtained from the cornea (n = 5 horses), eyelid (5), and third eyelid (5). Site-matched control tissues were obtained from 5 horses unaffected with SCC. Tissue sections of affected and control cornea, eyelid, and third eyelid were stained immunohistochemically for COX-1 and COX-2 via standard techniques. Stain uptake was quantified by use of computer-assisted image analysis of digital photomicrographs. RESULTS: Immunoreactivity for both COX-1 and COX-2 was significantly greater in equine corneas with SCC than in control corneas. No significant differences in COX-1 or COX-2 immunoreactivity were detected in eyelid and third-eyelid SCC, compared with site-matched control tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Immunoreactivity for COX-1 and COX-2 is high in equine corneal SCC, possibly indicating that COX plays a role in oncogenesis or progression of this tumor type at this site. Pharmacologic inhibition of COX may represent a useful adjunctive treatment for corneal SCC in horses. PMID- 17269881 TI - Evaluation of a combination of sodium hypochlorite and polyhexamethylene biguanide as an egg wash for red-eared slider turtles (Trachemys scripta elegans) to suppress or eliminate Salmonella organisms on egg surfaces and in hatchlings. AB - OBJECTIVE: To evaluate a combination of 2 nonantibiotic microbicide compounds, sodium hypochlorite (NaOCl) and polyhexamethylene biguanide (PHMB), as a treatment to suppress or eliminate Salmonella spp from red-eared slider (RES) turtle (Trachemys scripta elegans) eggs and hatchlings. SAMPLE POPULATION: 2,738 eggs from 8 turtle farms in Louisiana. PROCEDURES: Eggs were randomly sorted into 3 or, when sufficient eggs were available, 4 treatment groups as follows: control, pressure-differential egg treatment with NaOCl and gentamicin, NaOCl and PHMB bath treatment, and pressure-differential egg treatment with NaOCl and PHMB. Bacterial cultures were performed from specimens of eggs and hatchlings and evaluated for Salmonella spp. RESULTS: RES turtle eggs treated with NaOCl and PHMB as a bath (odds ratio [OR], 0.2 [95% confidence interval (CI), 0.1 to 0.3]) or as a pressure-differential dip (OR, 0.01 [95% CI, 0.001 to 0.07]) or with gentamicin as a pressure-differential dip (OR, 0.1 [95% CI, 0.06 to 0.2]) were significantly less likely to have Salmonella-positive culture results than control-group eggs. CONCLUSIONS AND CLINICAL RELEVANCE: Concern over reptile associated salmonellosis in children in the United States is so great that federal regulations prohibit the sale of turtles that are < 10.2 cm in length. Currently, turtle farms treat eggs with gentamicin solution. Although this has reduced Salmonella shedding, it has also resulted in antimicrobial resistance. Results of our study indicate that a combination of NaOCl and PHMB may be used to suppress or eliminate Salmonella spp on RES turtle eggs and in hatchlings. PMID- 17269883 TI - Effects of porcine small intestinal submucosa on elution characteristics of gentamicin-impregnated plaster of Paris. AB - OBJECTIVE: To evaluate effects of small intestinal submucosa (SIS) on elution properties of plaster of Paris (POP). SAMPLE POPULATION: 27 POP cylinders, 27 POP spheres, and 9 polymethylmethacrylate (PMMA) spheres. PROCEDURES: Pellets were loaded with gentamicin (50 mg/g) and divided into 7 groups of 9 beads each: PMMA spheres; POP cylinders coated with 0, 4, or 8 layers of SIS; and POP spheres coated with 0, 4, or 8 layers of SIS. Gentamicin concentration was measured 6, 12, 18, 24, 32, 40, and 48 hours and 3, 4, 5, 7, 14, 21, 28, 35, and 42 days after wrapping. Porosity was evaluated via scanning electron microscopy. Curvature factor of elution curves, total amount of drug released (TDR), time required to reach 50% of total release (TDR(t50)), and number of days with concentrations > or = 1 microg/mL were compared among groups. RESULTS: SIS decreased the curvature factor and increased the TDR(t50) and TDR of POP spheres and cylinders. Curvature factor of the PMMA-release curve remained lower than that for any POP group, but all POP groups wrapped in SIS released more gentamicin than PMMA spheres. Gentamicin concentrations remained > or = 1 microg/mL in SIS-wrapped POP and PMMA groups throughout the study. Wrapping POP in SIS minimized the increase in porosity of pellets. CONCLUSIONS AND CLINICAL RELEVANCE: Wrapping POP with SIS slows the release and increases the amount of gentamicin leaching from spheres and cylinders. All groups wrapped in SIS maintained antimicrobial concentrations greater than the minimum inhibitory concentration of most pathogens. PMID- 17269884 TI - Evaluation of the repeatability of rhinomanometry and its use in assessing transnasal resistance and pressure in dogs. AB - OBJECTIVE: To evaluate a modified posterior rhinomanometric method for clinical application in dogs. ANIMALS: 15 healthy Beagles and 8 Bulldogs (4 healthy and 4 with respiratory problems). PROCEDURES: Rhinomanometry was performed 3 times within a 15-minute period in anesthetized dogs. Transnasal pressure (P(NA)) and nasal resistance (R(NA)) were determined by use of artificial airflow (adjusted for body weight) for inspiration (P(NAin) and R(NAin), respectively) and expiration (P(NAout) and R(NAout)). Procedures were repeated for the Beagles 7 days later. RESULTS: For the Beagles, mean +/- SD of P(NAin) for both days (0.162 +/- 0.042 kPa) was significantly lower than P(NAout) (0.183 +/- 0.053 kPa). Similarly, R(NAin) (1.47 +/- 0.41 kPa/[L/s]) was significantly lower than R(NAout) (1.64 +/- 0.46 kPa/[L/s]). Pairwise comparison of values for P(NA) and R(NA) for the 2 days revealed no significant difference. Repeatability of the method (estimated as within-day variation) for R(NA) was +/- 0.19 kPa/(L/s), whereas variation between the days was +/- 0.36 kPa/(L/s) for R(NAin) and +/- 0.44 kPa/(L/s) for R(NAout). The 4 clinically normal Bulldogs had R(NA) values ranging from 1.69 to 3.48 kPa/(L/s), whereas in the 4 Bulldogs with respiratory problems, R(NA) ranged from 9.83 to 20.27 kPa/(L/s). CONCLUSIONS AND CLINICAL RELEVANCE: R(NA) is inversely dependent on body size and nonlinearly associated with airflow. We propose that R(NA) in dogs should be determined for airflows standardized on the basis of body size. The P(NA) and R(NA) in Beagles can be measured with sufficient repeatability for clinical use and nasal obstructions are detectable. PMID- 17269885 TI - Influx of neutrophils and persistence of cytokine expression in airways of horses after performing exercise while breathing cold air. AB - OBJECTIVE: To determine effects of exercise performed while breathing cold air on expression of cytokines and influx of neutrophils in airways of horses. ANIMALS: 9 adult horses. PROCEDURES: In a crossover study, bronchoalveolar lavage fluid (BALF) was obtained 24 and 48 hours after each of 2 submaximal exercise sessions performed by horses while breathing warm (25 degrees C) or cold (-5 degrees C) air. Total and differential nucleated cell counts were determined for each BALF sample. Relative mRNA expression of cytokines in BALF cells was quantified by use of a reverse transcription-PCR assay. RESULTS: Horses had a modest but significant influx of neutrophils into the airways 24 hours after a single exercise session while breathing cold air. No other cell types were increased at 24 or 48 hours after exercising while breathing cold air. Continued increases in expression of cytokines interleukin (IL)-5 and-10 as well as proinflammatory cytokines IL-1, -6, and -8 were detected 24 hours after exercising while breathing cold air. Forty-eight hours after exercising while breathing cold air, expression of IL-10 was still higher than that for IL-10 after horses exercised while breathing warm air. Expression of tumor necrosis factor-alpha was significantly increased at 48 hours after exercising while breathing cold air. CONCLUSIONS AND CLINICAL RELEVANCE: Exposure of intrapulmonary airways to cold air alters immunologic responses of horses for at least 48 hours. The increased expression of cytokines that suppress cell-mediated immunity may predispose athletes to viral infections of the respiratory tract following exercise in cold weather. PMID- 17269887 TI - In vivo evaluation of alpha(2)-adrenoceptors in cats with idiopathic cystitis. AB - OBJECTIVE: To evaluate the in vivo response of alpha(2)-adrenoceptors to medetomidine administration in cats with feline idiopathic cystitis (FIC) during periods of stress and after environmental enrichment. ANIMALS: 13 cats with FIC and 12 healthy cats. Procedures-Cats were subjected to an acute-onset moderate stressor for 8 days. After stress, 20 microg of medetomidine/kg was administered IM on days 1, 3, and 8. Heart rate, blood pressure, pupil diameter, respiratory rate, and level of sedation were evaluated before and after administration of the drug. After day 8, cats were moved to an enriched environment, and tests were repeated on day 35. RESULTS: Heart rate decreased and pupil diameter increased significantly after medetomidine administration in healthy cats, compared with cats with FIC. Cats with FIC had significantly lower respiratory rates. No significant differences in blood pressure or sedation level were found. CONCLUSIONS AND CLINICAL RELEVANCE: Increased plasma catecholamine concentrations during the enrichment phase, which have been reported elsewhere, may have contributed to the differences in alpha(2)-adrenoceptor responses detected in cats with FIC. PMID- 17269886 TI - Ocular and systemic manifestations after oral administration of a high dose of enrofloxacin in cats. AB - OBJECTIVE: To characterize the effects of oral administration of a high dose of enrofloxacin to cats. ANIMALS: 24 (12 male and 12 female) young healthy cats. PROCEDURES: Cats were allocated on the basis of sex into 2 groups (4 males and 4 females/ group) from which 3 subgroups for 3 durations (3, 5, or 7 days) of enrofloxacin (50 mg/kg, PO, q 24 h) or control solution (1 mL of water, PO, q 24 h) administration that began on day -1 were created. Funduscopic examinations were performed daily. Electroretinography (ERG) was performed before and every 2 to 3 days after the start of oral administration. Four cats/study group were euthanized on days 3, 5, and 7, and eyes were collected for light and electron microscopic evaluations. RESULTS: Neurologic, funduscopic, and ERG abnormalities were evident only in cats administered enrofloxacin. Funduscopic changes (granular appearance or graying of the area centralis) were noticed on or before day 3 (after only 3 days of enrofloxacin administration), with subsequent similar changes along the visual streak. Vascular attenuation (between days 2 and 4) and generalized tapetal hyperreflectivity (between days 5 and 7) followed. Reduction in b-wave ERG amplitude preceded funduscopic changes. Morphologic changes in the photoreceptor layers correlated with duration of enrofloxacin administration, with generalized degenerative changes evident after 3 doses. CONCLUSIONS AND CLINICAL RELEVANCE: The study indicated that a high dose of enrofloxacin (50 mg/kg/d, PO) induced retinal and systemic changes. Enrofloxacin at 10 times the recommended dosage is acutely toxic to the outer retina of clinically normal cats. PMID- 17269888 TI - Evaluation of the ability of canarypox-vectored equine influenza virus vaccines to induce humoral immune responses against canine influenza viruses in dogs. AB - OBJECTIVE: To evaluate canarypox-vectored equine influenza virus (EIV) vaccines expressing hemagglutinins of A/equine/Kentucky/94 (vCP1529) and A2/equine/Ohio /03 (vCP2242) for induction of antibody responses against canine influenza virus (CIV) in dogs. ANIMALS: 35 dogs. PROCEDURES: Dogs were randomly allocated into 4 groups; group 1 (n = 8) and group 2 (9) were inoculated SC on days 0 and 28 with 1.0 mL (approx 10(5.7) TCID(50)) of vCP1529 and vCP2242, respectively. Dogs in group 3 (n = 9) were inoculated twice with 0.25 mL (approx 10(5.7) TCID(50)) of vCP2242 via the transdermal route. The 9 dogs of group 4 were control animals. All dogs were examined for adverse reactions. Sera, collected on days -1, 7, 13, 21, 28, 35, and 42, were tested by hemagglutination inhibition (HI) and virus neutralization (VN) assays for antibodies against CIV antigens A/Canine/FL/43/04 PR and A/Canine/NY/115809/05, respectively. RESULTS: Inoculations were tolerated well. The HI and VN antibodies were detected by 7 days after primary inoculation. Most dogs of groups 1 and 2 and all dogs of group 3 had detectable antibodies by 14 days after initial inoculation. The second inoculation induced an anamnestic response, yielding geometric mean HI titers of 139, 276, and 1,505 and VN titers of 335, 937, and 3,288 by day 42 (14 days after booster inoculation) in groups 1, 2, and 3, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Canarypox-vectored EIV vaccines induce biologically important antibodies and may substantially impact CIV transmission within a community and be of great value in protecting dogs against CIV-induced disease. PMID- 17269890 TI - Genetic polymorphisms of drug-metabolizing enzymes and the susceptibility to antituberculosis drug-induced liver injury. AB - Three first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury ranges from a mild to severe form, and the associated mortality cases are not rare. The major drug-metabolizing enzyme of isoniazid is N acetyltransferase. Other possible enzymes are CYP2E1 and glutathione S transferase. There is evidence that polymorphisms of the genes that encode these enzymes may influence the activity of the corresponding drug-metabolizing enzymes. Recent studies demonstrated that these genetic polymorphisms may be associated with the susceptibility to antituberculosis drug-induced liver injury. The proposed risk-associated genotypes are NAT2 slow acetylator (without wild type NAT2*4 allele), CYP2E1 *1A/*1A (homozygous wild type) and homozygous null GSTM1 genotype. Although the available data in the field are still limited and warrants further confirmation in different ethnic populations with larger sample sizes, it still cast some light on the application of these pharmacogenetic or pharmacogenomic approaches to prevent grave antituberculosis drug-induced liver injury in the near future. PMID- 17269889 TI - Efficacy of a canarypox-vectored recombinant vaccine expressing the hemagglutinin gene of equine influenza H3N8 virus in the protection of ponies from viral challenge. AB - OBJECTIVE: To determine onset and duration of immunity provided by a 2- or 3-dose series of a new canarypox-vectored recombinant vaccine for equine influenza virus (rCP-EIV vaccine) expressing the hemagglutinin genes of influenza H3N8 virus strains A/eq/Kentucky/94 and A/eq/Newmarket/2/93 in ponies. ANIMALS: Forty-nine 1 to 3-year-old male Welsh Mountain Ponies that were seronegative for equine influenza virus. PROCEDURES: Vaccinated and control ponies were challenged with aerosolized influenza virus A/eq/Sussex/89 (H3N8), representative of the Eurasian lineage of circulating influenza viruses. In trial 1, control ponies and ponies that received rCP-EIV vaccine were challenged 2 weeks after completion of the 2 dose primary vaccination program. In trial 2, ponies were challenged 5 months after 2 doses of rCP-EIV vaccine or 1 year after the first boosting dose of rCP EIV vaccine, administered 5 months after completion of the primary vaccination program. After challenge, ponies were observed daily for clinical signs of influenza and nasal swab specimens were taken to monitor virus excretion. RESULTS: The challenge reliably produced severe clinical signs consistent with influenza infection in the control ponies, and virus was shed for up to 7 days. The vaccination protocol provided clinical and virologic protection to vaccinates at 2 weeks and 5 months after completion of the primary vaccination program and at 12 months after the first booster. CONCLUSION AND CLINICAL RELEVANCE: The rCP EIV vaccine provided protection of ponies to viral challenge. Of particular importance was the protection at 5 months after the second dose, indicating that this vaccine closes an immunity gap between the second and third vaccination. PMID- 17269891 TI - Antipsychotic drugs and QTc prolongation: the potential role of CYP2D6 genetic polymorphism. AB - Although the most common, and usually serious, side effects of first-generation (or typical) antipsychotic drugs, such as Parkinsonism, dystonias and tardive dyskinesia, were known from early times, their cardiovascular safety was not properly in the focus of treatment management. The growing evidence of these drug related cardiac changes and the appearance of potentially fatal dysrhythmias have increased the interest on their safety profile. Thus, the introduction of the new second-generation (atypical) antipsychotic drugs put emphasis on the preregistration evaluation of the potential cardiac side effects and electrocardiogram predictors (QT interval lengthening). In spite of this, these drugs do not appear to be exempt from these potential risks. The present review summarizes up-to-date knowledge about the cardiac safety of antipsychotic drugs, and analyses the role of drug metabolic processes (CYP2D6 genetic polymorphism) in the complex pathophysiology of the phenomenon. In addition, some recommendations are formulated. PMID- 17269892 TI - The impact of CYP allelic variation on antidepressant metabolism: a review. AB - Psychiatric diseases that are treated with antidepressants are the leading causes of morbidity and mortality in humankind. Although antidepressants are generally well tolerated and widely available, they are not equally effective in all patients and only 35 - 45% of patients treated for depression with these drugs recover to premorbid levels of functioning. There is a need for an effective, individualized approach to antidepressant selection. One promising lead in the development of personalized medicine is the emerging field of pharmacogenomics, whereby pharmacologic agents are selected on the basis of the genotype of patients, with particular attention to drug targets and phase I- and phase II metabolizing enzymes. This review article focuses on phase I antidepressant metabolizing enzymes (e.g., relevant CYP enzymes). The authors first briefly review CYP nomenclature, the relevant members of the CYP superfamily and their alleles, the metabolic categories and CYP antidepressant substrates, inhibitors and inducers. The literature on the impact of CYP polymorphisms on antidepressant metabolism are also reviewed. PMID- 17269893 TI - Cellular proteolytic systems in P450 degradation: evolutionary conservation from Saccharomyces cerevisiae to mammalian liver. AB - Mammalian hepatic cytochromes P450 (P450s) are endoplasmic reticulum (ER) anchored haemoproteins with the bulk of their catalytic domains exposed to the cytosol and engaged in the metabolism of numerous xeno- and endobiotics. The native P450s exhibit widely ranging half-lifes and predominantly turn over via either autophagic-lysosomal degradation (ALD) or ubiquitin-dependent 26S proteasomal degradation (UPD). The basis for this heterogeneity and differential proteolytic targeting is unknown. On the other hand, structurally/functionally inactivated P450s are predominantly degraded via UPD in a process known as ER associated degradation (ERAD). ALD/UPD/ERAD pathways are evolutionarily highly conserved. The availability of Saccharomyces cerevisiae mutants with specific genetic defects/deletions in various ALD/UPD/ERAD-associated proteins and corresponding isogenic wild-type strains has enabled the molecular dissection of the degradation pathways for heterologously expressed mammalian P450s, leading to the identification of specific protein participants. These findings collectively attest to a highly versatile cellular system for the physiological disposal of native, senescent and/or inactivated, structurally damaged mammalian liver P450s. PMID- 17269894 TI - Time-dependent CYP inhibition. AB - Time-dependent inhibition (TDI) of CYP refers to a change in potency during an in vitro incubation or dosing period in vivo. Potential mechanisms include the formation of inhibitory metabolites and mechanism-based inhibition (MBI). In vitro experiments are configured to assess TDI and MBI is inferred, at least initially. MBI is more profound after multiple-dosing and the recovery period is independent of continued drug exposure. Advances in in vitro-in vivo extrapolations for competitive inhibition and the potential relationship between MBI and reactive metabolite-mediated toxicity, have redirected emphasis to CYP TDI. In contrast, with reversible inhibition, strategies for projecting the risks from TDI are less developed and the traditional I/K(i) model often yields a dramatic underprediction. This review explores the contribution of TDI to drug drug interactions and idiosyncratic drug toxicity. PMID- 17269895 TI - Clinical relevance of the small intestine as an organ of drug elimination: drug fruit juice interactions. AB - Most drugs are taken orally. For those intended to act systemically, a significant fraction of the dose can be eliminated during its first passage through a sequence of organs before entry into the general circulation. For some drugs, the degree of first-pass elimination can be large enough such that oral bioavailability is significantly reduced, with the consequent potential for a reduced clinical response. Of these first-pass eliminating organs, the small intestine and liver are the most commonly implicated, in part because they express the highest levels of drug-metabolizing enzymes. For several drugs whose major route of elimination occurs via CYP3A-mediated metabolism, the extent of first-pass metabolism in the small intestine can rival that in the liver. As such, alterations in enteric CYP3A activity alone can significantly influence oral bioavailability. The most extensively studied xenobiotic shown to inhibit only enteric CYP3A is grapefruit juice, the consequences of which can be clinically significant. Although much information has been gained regarding the grapefruit juice effect, progress in the relatively understudied area of drug diet interactions continues to be sluggish and reactive. In stark contrast, the potential for drug-drug interactions involving any new therapeutic agent must be evaluated, prospectively, before market introduction. To prospectively elucidate mechanisms underlying drug-diet interactions, a multidisciplinary, translational research approach is required, which capitalizes on the collective expertise of drug metabolism scientists and natural products chemists. Such an approach would allow proper between-study comparisons, and ultimately provide conclusive information as to whether specific dietary substances can be taken safely with certain medications. PMID- 17269897 TI - Intestinal UGTs as potential modifiers of pharmacokinetics and biological responses to drugs and xenobiotics. AB - Uridine 5'-diphosphate-glucuronosyltransferases (UGTs) are the biological catalysts of glucuronidation, a major pathway of conjugative metabolism of drugs and xenobiotics. In addition to the liver and kidney, UGTs are highly expressed in the gastrointestinal tract, where they have the potential to influence the pharmacokinetics and biological effects of ingested drugs and xenobiotics. This paper reviews the current evidence for the contributions of intestinal UGTs to presystemic 'first-pass' metabolism and drug bioavailability, the extent of enterohepatic cycling and the clearance of drugs from plasma, as well as their influence on biological responses to drugs, including drug toxicity. The prediction of the effects of intestinal glucuronidation on these processes depends on knowledge of the types and amounts of UGTs expressed in the small intestine and their specific glucuronidating activities. Whereas the types of UGTs expressed in human gastrointestinal tract are well characterized, further research is needed to understand the absolute amounts of UGTs in the small intestine and the causes of observed high-interindividual variability in the intestinal expression of UGTs. PMID- 17269896 TI - Transporter-mediated drug interactions: clinical implications and in vitro assessment. AB - Although they are less frequently compared with the reported cases of CYP mediated drug interactions, clinically significant transporter-mediated drug interactions, which are mainly based on efflux transporter or P-glycoprotein data, have been reported. Unlike the CYP-mediated drug interactions that can be readily defined by inhibition or induction of CYP enzymes, the evidence for the so-called transporter-mediated drug interactions is often less conclusive. The difficulty in defining transporter-mediated drug interactions is due mainly to the interplay between transporters and drug-metabolizing enzymes in drug disposition, and the lack of specific and potent inhibitors for each transporter and enzyme. An important lesson learned from animal studies is that transporter inhibition has a much greater impact on the tissue distribution of drugs than on the systemic exposure of drugs measured in plasma. The potential risk of transporter-mediated drug interactions might be underestimated if only plasma concentrations are monitored. PMID- 17269898 TI - Toxicological and clinical computational analysis and the US FDA/CDER. AB - In this article the author attempts to introduce those not familiar with computational toxicology to some of the terminology and basic principles of the field. The author then reports on the progress that the FDA, Center for Drug Evaluation and Research has made in compiling databases of toxicological and clinical data from which successful predictive toxicology models have been made, many of which are now commercially available through FDA software developer collaborators. This report is concluded with the author's personal speculations on the future of computational toxicology in general, and at US FDA in particular. PMID- 17269899 TI - In silico approaches to explore toxicity end points: issues and concerns for estimating human health effects. AB - The European Chemicals Bureau and the Organisation for Economic Cooperation and Development are currently compiling a sanctioned list of quantitative structure activity relationship (QSAR) risk assessment models and data sets to predict the physiological properties, environmental fate, ecological effects and human health effects of new and existing chemicals in commerce in the European Union. This action implements the technical requirements of the European Commission's Registration, Evaluation and Authorisation of Chemicals legislation. The goal is to identify a battery of QSARs that can furnish rapid, reliable and cost effective decision support information for regulatory decisions that can substitute for results from animal studies. This report discusses issues and concerns that need to be addressed when selecting QSARs to predict human health effect end points. PMID- 17269900 TI - A brief review of the pharmacologic and therapeutic aspects of memantine in Alzheimer's disease. AB - The past decade has seen an increase in therapeutic options for Alzheimer's disease (AD) that target neurotransmitters, such as acetylcholine, and research continues to target abnormal proteins in the AD brain. Recently, glutamate excitotoxicity has also become a target for AD treatment with the advent of memantine. Clinical trial data reviewed for memantine show good tolerability, low side-effect profiles and a positive therapeutic impact in moderate-to-severe AD, both as monotherapy and in conjunction with donepezil. However, additional data suggest variable benefits in the mild stages of AD. Furthermore, published reports support reduced dosing in patients with significant renal disease. However, the opportunity to target a second mechanism in the treatment of AD, thereby providing added symptomatic benefit, appears to be a useful consideration for clinicians who treat this devastating neurodegenerative disorder. PMID- 17269901 TI - Microfluidic large-scale integration: the evolution of design rules for biological automation. AB - Microfluidic large-scale integration (mLSI) refers to the development of microfluidic chips with thousands of integrated micromechanical valves and control components. This technology is utilized in many areas of biology and chemistry and is a candidate to replace today's conventional automation paradigm, which consists of fluid-handling robots. We review the basic development of mLSI and then discuss design principles of mLSI to assess the capabilities and limitations of the current state of the art and to facilitate the application of mLSI to areas of biology. Many design and practical issues, including economies of scale, parallelization strategies, multiplexing, and multistep biochemical processing, are discussed. Several microfluidic components used as building blocks to create effective, complex, and highly integrated microfluidic networks are also highlighted. PMID- 17269902 TI - Predicting physical activity among low-income Mexican American women: application of the theory of planned behavior. AB - OBJECTIVES: To utilize the theory of planned behavior (TPB) in explaining the prediction of physical activity intention and determine if present activity behavior attenuates theory construct relationships in a sample of low-income Mexican women. METHODS: Data were gathered on 201 subjects through a self-report survey instrument and analyzed through structural equation modeling. RESULTS: Present activity behavior attenuated theory construct influence on intention, and perceived behavioral control was the strongest predictor of intent to engage in physical activity. CONCLUSIONS: Interventions promoting voluntary physical activity for this population group should address factors perceived as barriers to participating in activity situations. PMID- 17269903 TI - The theory of reasoned action and intention to seek cancer information. AB - OBJECTIVES: To evaluate the applicability of the theory of reasoned action to explain men's intentions to seek prostate cancer information. METHODS: Three hundred randomly selected African American men participated in telephone interviews. Correlational and regression analyses were conducted to examine relationships among measures. RESULTS: All relationships were significant in regression analyses. Attitudes and subjective norm were significantly related to intentions. Indirect measures of beliefs derived from elicitation research were associated with direct measures of attitude and subjective norms. CONCLUSIONS: The data are sufficiently clear to support the applicability of the theory for this behavioral domain with African American men and suggest several important areas for future research. PMID- 17269904 TI - Psychosocial predictors of increases in fruit and vegetable consumption. AB - OBJECTIVES: To examine psychosocial predictors of changes in fruit and vegetable consumption. METHODS: Baseline psychosocial variables were used to explain differences in changes in consumption in 83 healthy women with children after they received free fruit and vegetables for one month. RESULTS: One-month changes in fruit consumption (mean 144; SE 16 g/day) were positively associated with perceived costs and perceived health benefits for the children, and negatively associated with perceived behavioral control. Changes in vegetable consumption (68 (11) g/day) were positively related with the intention to eat at least 200 g of vegetables and taste preferences of the children. CONCLUSIONS: Fruit and vegetable consumption may be encouraged by influencing the above variables. PMID- 17269905 TI - Exploring Latino men's HIV risk using community-based participatory research. AB - OBJECTIVES: To explore sociocultural determinants of HIV risk and identify potential intervention approaches among adult Latino men. METHODS: Using community-based participatory research for study design and implementation and data analysis, 7 focus groups were conducted with members of a soccer league in central North Carolina. RESULTS: Five themes emerged, including perceived barriers to accessing health care, the role of hegemonic masculinity in risk, and potentially effective intervention approaches to health promotion and disease prevention. CONCLUSIONS: Latino soccer leagues may provide an effective social network with which to partner to design, implement, and evaluate interventions to reduce sexual risk among Latino men, who have been inaccessible in conventional HIV/ STD prevention programs. PMID- 17269906 TI - Levels and correlates of exercise in a border mexican american population. AB - OBJECTIVE: To examine personal and environmental correlates of exercise among Mexican Americans living in the Texas-Mexico border region. METHODS: The study was based on data from a community health assessment conducted in 2 counties at the Texas-Mexico border region. A random-digit-dialed community survey was used in this cross-sectional study (n=933). RESULTS: A majority of border Mexican Americans (52%) did not exercise at all. Gender, age, and self-rated health were statistically significant correlates to exercise. CONCLUSIONS: Understanding personal and environmental factors that influence physical activity and exercise in this minority population is critical for the development of culturally sensitive health interventions. PMID- 17269907 TI - Denormalizing a historical problem: teen pregnancy, policy, and public health action. AB - OBJECTIVE: To explore the impact of teen-adult sexual relationships as a public health threat and the effectiveness of statutory rape laws in protecting adolescent children. METHODS: A comprehensive review of current literature surrounding child abuse, teen pregnancy, and statutory rape was conducted. RESULTS: Of one million teen girls who become pregnant each year, two-thirds may be the victims of statutory rape. Current laws appear to marginalize the severity of teen- adult sexual relationships, compromising the health and safety of adolescent children. CONCLUSIONS: Public health recommendations which include public policy change and enforcement, education, and community empowerment are offered. PMID- 17269908 TI - Who are health influencers? Characterizing a sample of tobacco cessation interveners. AB - OBJECTIVES: To describe characteristics of health influencers (HIs) prior to training in brief tobacco cessation interventions (BI). METHODS: HIs (n=910) in Arizona were recruited for a randomized controlled trial comparing training modalities. RESULTS: Typically middle-aged (M=43, SD=14), non-Hispanic white (68%), female (77%), non-tobacco users (93%), most identified personal (89%) rather than job-related (3%) motivators for becoming cessation interveners. Confidence about intervention ability was high (93%); knowledge scores, however, were low (M=55%, SD=13%). CONCLUSIONS: HIs exhibiting high motivation to intervene but lacking knowledge about BI strategies may be an untapped resource for tobacco cessation and a variety of other health promotion interventions. PMID- 17269909 TI - Validation of the WHI brief physical activity questionnaire among women diagnosed with breast cancer. AB - OBJECTIVE: To investigate the psychometric properties of the physical activity (PA) measure of the Women's Health Initiative (WHI). METHODS: Women diagnosed with breast cancer and enrolled in the Women's Healthy Eating and Living Study (average age 55 years) wore an accelerometer for 1 week and completed the 7-day Physical Activity Recall (PAR) and brief WHI measure. RESULTS: Both self-reports correlated 0.73 with the accelerometer and had 100% sensitivity for meeting the current PA guideline, but specificity was significantly higher for the PAR. CONCLUSIONS: The WHI measure had comparable validity, sensitivity, and measurement bias compared to the widely accepted PAR. PMID- 17269910 TI - Physical activity and function in older adults: theory of planned behavior. AB - OBJECTIVE: To assess the theory of planned behavior (TPB) and TPB with functional ability to explain intention and self-reported physical activity (PA) behavior of older adults. METHODS: A survey was mailed to 2056 retirees from a large Midwestern university. RESULTS: Structural equation modeling revealed that the TPB plus functional ability explained an additional 11% variance than the TPB alone in older adult PA and functional ability was the best predictor of PA (beta = .53, P<.05). CONCLUSIONS: Functional ability appears to be an important predictor of PA behavior and should be included when designing PA programs for older adults. PMID- 17269911 TI - Neighborhood deprivation and health risk behaviors in NHANES III. AB - OBJECTIVE: To examine whether neighborhood-level socioeconomic status is an independent risk factor for health risk behaviors. METHODS: Data from the Third National Health and Nutrition Examination Survey were linked with census tracts from the 1990 US Census. Outcome variables included biomarkers for smoking and high dietary fat intake, and self-reported excessive alcohol consumption and physical inactivity. RESULTS: Multivariate logistic regression showed an association between high levels of neighborhood deprivation and increased odds of health risk behaviors independent of sociodemographic factors, BMI, and comorbidities. CONCLUSION: Living in highly deprived neighborhoods is associated with risky health behaviors. PMID- 17269912 TI - Iontophoresis - an approach for controlled drug delivery: a review. AB - The recent approval of lidocaine hydrochloride and epinephrine combined iontophoretic patch (Lidosite Vysteris Inc.) for localized pain treatment by FDA has invigorated the gaining interest in iontophoretic drug delivery systems for the transdermal delivery of drugs. This technique of facilitated movement of ions across a membrane under the influence of an externally applied electric potential difference, is one of the most promising physical skin penetration enhancing method. The rationale behind using this technique is the capability of this method to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability, which is otherwise achieved only when parentral route of administration is used. Recently, good permeation of larger peptides like insulin has been achieved through this technique in combination with chemical enhancers. This review briefly describes the factors which affect iontophoretic drug delivery and summarizes the studies conducted recently using this technique in order to achieve higher systemic absorption of the drugs having low passive diffusion otherwise. The effect of permeation enhancers (chemical enhancers) on iontophoretic flux of drugs has also been described. Present review also provides an insight into reverse iontophoresis. Various parameters which affect the transdermal absorption of drugs through iontophoresis like drug concentration, polarity of drugs, pH of donor solution, presence of co-ions, ionic strength, electrode polarity etc. have also been reviewed in detail. PMID- 17269913 TI - PEGylated dendritic architecture for development of a prolonged drug delivery system for an antitubercular drug. AB - The present study was aimed at developing and exploring the use of PEGylated poly (propylene imine) dendritic architecture for the delivery of an anti-tuberculosis drug, rifampicin. For this study, PEGylated poly(propylene imine) dendritic architecture was synthesized and loaded with rifampicin. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release and hemolytic toxicity of both PEGylated and non-PEGylated systems were determined and compared. The PEGylation of the systems was found to have increased their drug-loading capacity, reduced their drug release rate and hemolytic toxicity. The systems were found suitable for prolonged delivery of rifampicin. PMID- 17269914 TI - Investigation of enhancement of solubility of norfloxacin beta-cyclodextrin in presence of acidic solubilizing additives. AB - The present study is aimed at improving the solubility of a poorly water-soluble drug, norfloxacin by incorporating solubilizing additives such as ascorbic acid and citric acid into the beta-cyclodextrin complexes. Norfloxacin, being amphoteric in nature, exhibits a higher solubility at pH below 4 and above 8. Addition of substances like ascorbic acid and citric acid in beta-cyclodextrin complexes reduces the pH of the immediate microenvironment of the drug below pH 4. In the present work, beta-cyclodextrin complexes of norfloxacin were prepared along with solubilizing additives such as citric acid and ascorbic acid in various proportion and the dissolution profile was performed in both HCl buffer, pH 1.2 and phosphate buffer, pH 7.4. The results have shown an enhanced dissolution rate in both media. DSC and IR spectral studies performed on the solid complexes have shown that there is no interaction of the drug with the additives and beta-cyclodextrin. Disc diffusion studies have shown larger diameters of zone of inhibition indicating a greater diffusivity of the drug into the agar medium. PMID- 17269915 TI - Development of mucoadhesive patches for buccal administration of carvedilol. AB - A buccal patch for systemic administration of carvedilol in the oral cavity has been developed using two different mucoadhesive polymers. The formulations were tested for in vitro drug permeation studies, buccal absorption test, in vitro release studies, moisture absorption studies and in vitro bioadhesion studies. The physicochemical interactions between carvedilol and polymers were investigated by Fourier transform infrared (FTIR) Spectroscopy. According to FTIR the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. XRD studies reveal that the drug is in crystalline state in the polymer matrix. The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared. Bioavailability studies in healthy pigs reveal that carvedilol has got good buccal absorption. The bioavailability of carvedilol from buccal patches has increased 2.29 folds when compared to that of oral solution. The formulation AC5 (HPMC E 15) shows 84.85 + 0.089% release and 38.69 + 6.61% permeated through porcine buccal membrane in 4 hr. The basic pharmacokinetic parameters like the C(max), T(max) and AUC(total) were calculated and showed statistically significant difference (P<0.05) when given by buccal route compared to that of oral solution. PMID- 17269916 TI - Stomach specific anti-helicobacter pylori therapy: preparation and evaluation of amoxicillin-loaded chitosan mucoadhesive microspheres. AB - The purpose of this research was to formulate and systematically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use of treating gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing chitosan as mucoadhesive polymer were prepared by simple emulsification phase separation technique using glutaraldehyde as a cross-linking agent. Results of preliminary trials indicate that volume of cross-linking agent, time for cross-linking, polymer-to-drug ratio, and speed of rotation affected characteristics of microspheres. Microspheres were discrete, spherical, free flowing and also showed high percentage drug entrapment efficiency. In vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to gastric mucous layer and could retain in gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, polymer-to-drug ratio (X(1)), and stirring speed (X(2)) on dependent variables i.e. percentage mucoadhesion, t(80), drug entrapment efficiency, particle size and swelling index. The best batch exhibited a high drug entrapment efficiency of 70 % and a swelling index of 1.39; percentage mucoadhesion after 1 h was 79 %. The drug release was also sustained for more than 12 h. The polymer-to-drug ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied using scanning electron microscopy. In vitro release test showed that amoxicillin released slightly faster in pH 1.0 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin mucoadhesive microspheres and powder, to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make contribution complete eradication of H. pylori. PMID- 17269917 TI - Formulation and evaluation of famotidine floating tablets. AB - The purpose of this investigation was to prepare a gastroretentive drug delivery system of famotidine. Floating tablets of famotidine were prepared employing two different grades of methocel K100 and methocel K15M by effervescent technique; these grades of methocel were evaluated for their gel forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy and dissolution studies. The effect of citric acid on drug release profile and floating properties was investigated. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 6-10 hours. Decrease in the citric acid level increased the floating lag time but tablets floated for longer duration. A combination of sodium bicarbonate (130mg) and citric acid (10mg) was found to achieve optimum in vitro buoyancy. The tablets with methocel K100 were found to float for longer duration as compared with formulations containing methocel K15M. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed. PMID- 17269918 TI - Hepatitis-B surface antigen (HBsAg) powder formulation: process and stability assessment. AB - The purpose of this study was to develop a hepatitis-B surface antigen (HBsAg) dry powder vaccine formulation suitable for epidermal powder immunization (EPI) via an efficient, scalable powder-formation process. Several HBsAg dry powder formulations were prepared using four different powder-formation methods: freeze drying/compress/grind/sieve (FD/C/G/S), spray-drying (SD), agarose beads, and spray freeze-drying (SFD). Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Physical, chemical and biochemical stability of HBsAg was determined by dynamic light scattering, an enzyme immune assay, and immunogenicity in a mouse or hairless guinea pig model. Out of the four powder-formation methods evaluated SFD outperformed other methods in the following considerations: good process efficiency, flexible scalability, and desirable particle characteristics for skin penetration. The stress posed by SFD appeared to be mild as HBsAg in the dry form retained its potency and immunogenicity. Notably, the mechanism of fast freezing by SFD actually promoted the preservation of HBsAg nanoparticle size, in good correlation with long-term biochemical stability. Among several formulations screened, the formulation containing 10 microg HBsAg in 1-mg powder with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability performance. In conclusion, HBsAg dry powder formulations suitable for EPI were successfully prepared using SFD. Further, a systematic formulation development strategy allowed the development and optimization of an HBsAg dry powder formulation, demonstrating excellent long-term physical, biochemical, and immunological stability. PMID- 17269919 TI - Development of nitrendipine transdermal patches: in vitro and ex vivo characterization. AB - OBJECTIVE: The aim of the investigation was to develop and evaluate matrix type transdermal drug delivery systems (TDDS) of nitrendipine (NTDP). EXPERIMENTAL: The matrix type TDDS of NTDP were prepared by solvent evaporation technique. Ten formulations (composed of Eudragit RL 100 and Hydroxypropyl methyl cellulose in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4 in formulations A1, A2, A3, A4, A5 and Eudragit RS 100 and Hydroxypropyl methyl cellulose in the same ratios in formulation B1, B2, B3, B4, B5 respectively) were prepared. All formulations carried 6 % v/w of carvone as penetration enhancer and 15% v/w of propylene glycol as plasticizer in dichloromethane and methanol as solvent system. The prepared TDDS were evaluated for in vitro release, ex vivo permeation, moisture absorption, moisture content and mechanical properties. The physicochemical interactions between nitrendipine and polymers were investigated by Fourier Transform Infrared (FTIR) Spectroscopy. RESULTS: The maximum drug release in 24 hrs for A series formulations was 89.29% (A4) and 86.17% for B series (B5), which are significantly (p < 0.01) different to the lowest values (57.58 for A1 and 50.64 for B1). Again formulations A4 (flux 23.51 microg/hr/cm(2)) and B5 (flux 22.98 microg/hr/cm(2)) showed maximum skin permeation in the respective series. The flux obtained with formulation A4 and B5 meets the required flux (19.10 microg/hr/cm(2)). The mechanical properties, tensile strength, elastic modulus (3.42 kg/mm(2) for A4 and 4.25 kg/mm(2) for B5) reveal that the formulations were found to be strong but not brittle. FTIR studies did not show any evidence of interaction between the drug and the polymers. CONCLUSION: Nitrendipine matrix type transdermal therapeutic systems could be prepared with the required flux having suitable mechanical properties. PMID- 17269920 TI - Artificial organs: a new option for treating osteoarthritis. AB - Osteoarthritis is usually regarded as a localized disease whose optimal treatment is a therapy applied directly to the affected joint. Unfortunately, current local therapies such as repeated intraarticular injections or constant infusions are associated with a higher risk of infection. One way to overcome this would be to transfer substances made locally by cells within the joint. However, attempts using direct vector transfers or intraarticular injections of ex vivo modified cells could not achieve a sustained protein secretion over several months. Another method of delivering biological factors (i.e.growth hormones) intraarticularly is to transplant an artificial organ, capable of supporting the regeneration of natural cartilage, directly into the affected joint The main difficulty of having to produce bioactive factors over a long period of time is overcome by implanting a chamber-like system filled with either genetically modified cells or a drug-releasing matrix. This drug delivery system would be located at a peripheral site of the joint and could release substances directly into the joint cavity which would be transported via the synovial fluid and/or diffused to the chondrocytes or synoviocytes. PMID- 17269921 TI - Effects of lipid composition and preparation conditions on physical-chemical properties, technological parameters and in vitro biological activity of gemcitabine-loaded liposomes. AB - The effects of lipid composition and preparation conditions on the physicochemical and technological properties of gemcitabine-loaded liposomes, as well as the in vitro anti-tumoral activity of various liposome formulations were investigated. Three liposome formulations were investigated: DPPC/Chol/Oleic acid (8:3:1 molar ratio, liposomes A), DPPC/Chol/DPPS (6:3:1 molar ratio, liposomes B) and DPPC/Chol/DSPE-MPEG (6:3:1 molar ratio, liposomes C). Multilamellar liposomes were prepared by using the TLE, FAT and DRV methods, while small unilamellar liposomes were obtained by extrusion through polycarbonate filters. Light scattering techniques were used to characterize liposome formulations. Loading capacity and release profiles of gemcitabine from various liposome formulations were also investigated. Caco-2 cells were used to evaluate in vitro the antitumoral activity of gemcitabine-loaded liposomes with respect to the free drug and also the intracellular drug uptake. Preparation methods and liposome lipid composition influenced both physicochemical parameters and drug delivery features. Liposomes with a size ranging from 200 nm to 7 microm were obtained. The gemcitabine entrapment was higher than that expected probably due to an interaction with the liposome lipid components. The following decreasing loading capacity order was observed: liposome B>liposome C>liposome A. Gemcitabine release from various liposome formulations is modulated by two different processes, i.e. desorption from and permeation through liposomal bilayers. MTT assay showed a greater cytotoxic effect of gemcitabine-loaded liposomes with respect to the free drug. The following decreasing anticancer activity order was observed between the various liposome formulations: liposome C>liposome A>liposome B. The increased anticancer activity is correlated to the ability of the colloidal carrier to increase the intracellular drug uptake. Due to the encouraging results and to the high liposome modularity various applications of potential therapeutic relevance can be envisaged for liposomes. PMID- 17269923 TI - Design of second generation HIV-1 integrase inhibitors. AB - The prospect of HIV-1 integrase (IN) as a therapeutically viable retroviral drug target is on the verge of realization. The observed preclinical and clinical performance of beta-diketo containing and naphthyridine carboxamide compounds provides direct proof for the clinical application of IN inhibition. These validated lead compounds are useful in the design and development of second generation IN inhibitors. The results from preclinical and clinical studies on the first generation IN inhibitors reiterate a demand for novel second generation inhibitors with improved pharmacokinetic and metabolic properties. Pharmacophore based drug design techniques facilitate the discovery of novel compounds on the basis of validated lead compounds specific for a drug target. In this article we have comprehensively reviewed the application of pharmacophore-based drug design methods in the field of IN inhibitor discovery. PMID- 17269924 TI - HIV entry inhibitors targeting gp41: from polypeptides to small-molecule compounds. AB - HIV envelope glycoprotein transmembrane subunit gp41 plays a critical role in the fusion between viral and target cell membranes. Upon gp120 binding to CD4 and a coreceptor (CCR5 or CXCR4), gp41 changes its conformation by forming N-helix trimer between N-heptad repeats (NHRs) and then six-helix bundle between the N trimer and the C-heptad repeats (CHRs). Peptides derived from the NHR and CHR of gp41 extracellular region have demonstrated potent inhibitory activity on the HIV mediated cell fusion. One of these peptides, T-20, became the first success of a new class of anti-HIV agents, named HIV entry inhibitors. However, a relatively long peptide such as T-20 suffers from several limitations including lack of oral bioavailability and high cost of production. Great efforts have been made to develop alternative peptides and proteins with improved anti-HIV-1 activity, increased bioavailability and reduced cost of production. The most promising approach is the development of small molecule HIV entry inhibitors targeting gp41. Any molecule that blocks the process of NHR homotrimerization and the six helix bundle formation by targeting the gp41 NHR, NHR trimer and CHR may inhibit HIV-mediated membrane fusion. The progress in development of those anti-HIV agents targeting gp41, from polypeptides to small-molecule compounds, is reviewed. PMID- 17269925 TI - Chemokines and defensins as HIV suppressive factors: an evolving story. AB - When attacked by HIV, the immune system counteracts infection with elicitation of HIV-specific antibodies and cytotoxic T lymphocytes. In most cases however, these defenses are unable to resolve HIV infection, which progresses, if left untreated, ravaging the immune system and leading to AIDS and, eventually, to death. Nonetheless, there are additional components of the immune system, from both the innate and the adaptive components, that are associated with improved clinical status and, in some cases, even with protection from infection. Two distinct families of such factors have been studied in depth: chemokines and beta defensins. CCR5 chemokines, which are involved in adaptive immunity, are molecules produced by lymphocytes, and thus are likely to play a role in controlling HIV systemically. beta-defensins are instead produced by epithelial cells, and thus are important in controlling infection at mucosal sites. Both of these families of molecules, therefore, are involved in crucial battlegrounds for fighting HIV infection. Here, we review the evidence that argues for their importance in AIDS pathogenesis and in preventive and therapeutic approaches to combat HIV infection. PMID- 17269926 TI - Carbohydrate microarrays as tools in HIV glycobiology. AB - Progress in carbohydrate microarray technology has positioned the glycochip among the expanding set of biophysical tools available to researchers. Synthetically derived glycochips unite established microarray techniques with the versatility and structural precision of synthetic carbohydrate chemistry. A comprehensive demonstration of carbohydrate microarrays is illustrated by the chip-based study of protein/carbohydrate and protein/glycoprotein interactions as they relate to HIV glycobiology. Composed of a series of high-mannose oligosaccharides, carbohydrate microarrays were prepared utilizing a covalent linking strategy to immobilize synthetically-defined glycans in a uniform orientation. In concert with a simple glycoprotein array, these microarrays were used to establish the individual and competitive binding profiles of five gp120 binding proteins--DC SIGN, CD4, 2G12 cyanovirin-N, and scytovirin--and established the carbohydrate structural requirements for these interactions. PMID- 17269927 TI - Defining carbohydrate antigens as HIV vaccine candidates. AB - The induction of high affinity antibodies capable of broad neutralization and protection against infection and/or disease is a major goal in the development of a vaccine for human immunodeficiency virus (HIV). Insights into the structure and function of the envelope (Env) protein of HIV-1 suggest that the virus is under strong selection pressure by the immune response leading to constant mutations in the Env protein including the N-glycosylation sites. Initially considered a shield against the immune system, the heavily glycosylated outer surface of the HIV Env protein has drawn attention lately as a legitimate target. The dense cluster of high mannose glycans and the great variety of complex glycans present epitopes that might impact on disease progression. Indeed a number of mannose binding proteins and at least one human anti-mannose antibody--2G12, are broadly neutralizing. Due to the low immunogenicity of carbohydrates, these targets on HIV are of limited value unless new powerful immunogens are found. One approach would be the molecular design of peptide carbohydrate mimotopes that can elicit neutralizing antibodies by recruiting optimal T cell help. Here we review existing data on carbohydrate interactions and HIV immunogenicity that serves as a basis for structural concepts and approaches used for vaccine design targeting HIV associated carbohydrate antigens. In particular, the value and the limitations of chemical (peptide libraries), structural and immunological information is illustrated. PMID- 17269928 TI - Novel approaches for identification of broadly cross-reactive HIV-1 neutralizing human monoclonal antibodies and improvement of their potency. AB - Human monoclonal antibodies (hmAbs) that neutralize HIV isolates from different clades at physiologically relevant concentrations (broadly cross-reactive neutralizing antibodies (bcnAbs)) are rare in infected individuals. Only small number of such antibodies have been identified and extensively characterized, but efforts to elicit them in vivo have not been successful. We have recently developed novel approaches, based on sequential (SAP) and competitive (CAP) antigen panning methodologies, and the use of antigens with increased exposure of conserved epitopes, for enhanced identification of bcnAbs to gp120-gp41. Some of the antibodies identified by using these approaches (X5, m6, m9) bind better to gp120-CD4 complexes than to gp120 alone (CD4i antibodies); they exhibit exceptional neutralizing activity and breadth of neutralization as scFvs and on average lower potency as Fabs and IgGs. Other antibodies that compete with CD4 for binding to gp120 (m14, m18) (CD4bs antibodies) are weaker neutralizers but also exhibit broad neutralizing activity although at relatively high concentrations. The anti-gp41 antibodies (m43, m44, m45, m47 and m48) appear to have broad cross-reactivity and bind to a new group of conserved conformational epitopes distinct from those of the bcnAbs 4E10, 2F5 and Z13. Recently, the crystal structures of X5, m14 and m18 have been solved and compared to those of 17b and b12; they all contain long H3s that play a major role in their mechanism of binding. The H3s of X5, m6 and m9, unlike the others known, appear to be very flexible which may be related to the mechanism of their exceptional neutralizing activity. The further characterization of the molecular interactions of the bcnAbs with gp120-gp41 will undoubtedly help in our understanding of the mechanisms of virus neutralization, and in the design of entry inhibitors and vaccines. PMID- 17269929 TI - Rational modifications of HIV-1 envelope glycoproteins for immunogen design. AB - An effective vaccine against the human immunodeficiency virus type 1 (HIV-1) will likely require the elicitation of broadly neutralizing antibodies as well as cellular responses. The HIV exterior envelope glycoprotein trimers, gp120, and the transmembrane glycoprotein, gp41, mediate entry and are the sole viral targets for neutralizing antibodies. However, as subunit immunogens the envelope glycoproteins do not efficiently elicit antibodies capable of neutralizing the extremely diverse array of viruses circulating in the human population. The preponderance of data suggest that inefficient generation of broadly neutralizing antibodies is due to naturally evolved mechanisms of immune evasion inherent in the unmodified HIV envelope glycoproteins. Because the established modes of anti viral vaccine development, live-attenuation and virus inactivation have not yet been successful for HIV, we and others have focused on subunit vaccine design. In this review, we describe current approaches of rational modification of the envelope glycoproteins based upon structure, antigenicity, biochemistry and biophysics to alter the properties of the envelope glycoproteins such that, as subunit immunogens, they now better elicit broadly neutralizing antibodies. The application of structure-assisted, rational subunit vaccine design may be a general paradigm for future efforts to develop vaccines against emerging human pathogens. PMID- 17269930 TI - Atenolol: differences in mode of action compared with other antihypertensives. An opportunity to identify features that influence outcome? AB - The beneficial effect of antihypertensive treatment on the risk of major vascular events is well established. Several trials comparing older and newer drugs in the treatment of primary hypertension suggested that it is the blood pressure achieved, rather than choice of the drug that determines most of the primary outcomes. Beta-blockers have been widely used to treat hypertension and are still recommended as first-line drugs in guidelines. However, recent meta-analyses of trials (either placebo-controlled or using drug comparisons) involving atenolol (a popular beta-blocker), have cast doubt on the suitability of atenolol as a first-line antihypertensive drug. We consider the mechanisms which might be responsible for the inferiority of atenolol in preventing vascular morbidity and mortality in patients with primary hypertension. This knowledge may help design drugs that are not only more effective in achieving blood pressure targets but that also markedly decrease vascular events. PMID- 17269931 TI - Pharmacogenetics and drug therapy in psychiatry--the role of the CYP2D6 polymorphism. AB - The importance of pharmacogenetics in medicine is growing with the identification of genetic variability by faster screening methods using automatic sequencers. A particularly interesting finding is that apart from environmental and psychological factors, drug response may be influenced by several biological factors as a result of genetic determinants leading to interindividual variability. Several mutations in genes coding for enzymes of the drug metabolizing system, as well as for neurotransmitter receptors or degrading enzymes and monoamine transport proteins, have been identified and investigated in psychiatry. But, despite the fact that some genetic polymorphisms of enzymes (mainly cytochrome P450 2D6) are well known, the application of pharmacogenetics as a therapeutic tool for improving patient care is rare. This review has three parts. In the first an overview is given of CYP450 characteristics and the genetic polymorphisms of interest to psychiatry. In the second the clinical implications of the CYP2D6 polymorphism are reviewed and in the third part other aspects on pharmacogenetic research in psychiatry are discussed. The aim of our review is to promote the application of pharmacogenetics in everyday clinical practice. PMID- 17269934 TI - It is all about resolution. Meeting report based upon presentations at the 10th International Global BioMillennium 2006 symposium on molecular cell biology (Tbilisi, Georgia). AB - The 2006 Global BioMillennium Conference took place in Tbilisi, Georgia, on 13-17 July 2006. The Conference was focused on key aspects of gene expression processes. Characteristic of state-of-the-art research in the life sciences, the invited lectures spanned approaches in cell biology, gene expression, and protein function. A particular aspect that is special to the BioMillenium series of conferences (this has been the 10th in this series) is the emphasis on new and emerging technologies; the various experts in the subfields that were covered presented what, in their view, should be critical to enabling future progress. PMID- 17269932 TI - TLXI, a novel type of xylanase inhibitor from wheat (Triticum aestivum) belonging to the thaumatin family. AB - Wheat (Triticum aestivum) contains a previously unknown type of xylanase (EC 3.2.1.8) inhibitor, which is described in the present paper for the first time. Based on its >60% similarity to TLPs (thaumatin-like proteins) and the fact that it contains the Prosite PS00316 thaumatin family signature, it is referred to as TLXI (thaumatin-like xylanase inhibitor). TLXI is a basic (pI> or =9.3 in isoelectric focusing) protein with a molecular mass of approx. 18-kDa (determined by SDS/PAGE) and it occurs in wheat with varying extents of glycosylation. The TLXI gene sequence encodes a 26-amino-acid signal sequence followed by a 151 amino-acid mature protein with a calculated molecular mass of 15.6-kDa and pI of 8.38. The mature TLXI protein was expressed successfully in Pichia pastoris, resulting in a 21-kDa (determined by SDS/PAGE) recombinant protein (rTLXI). Polyclonal antibodies raised against TLXI purified from wheat react with epitopes of rTLXI as well as with those of thaumatin, demonstrating high structural similarity between these three proteins. TLXI has a unique inhibition specificity. It is a non-competitive inhibitor of a number of glycoside hydrolase family 11 xylanases, but it is inactive towards glycoside hydrolase family 10 xylanases. Progress curves show that TLXI is a slow tight-binding inhibitor, with a K(i) of approx. 60-nM. Except for zeamatin, an alpha-amylase/trypsin inhibitor from maize (Zea mays), no other enzyme inhibitor is currently known among the TLPs. TLXI thus represents a novel type of inhibitor within this group of proteins. PMID- 17269933 TI - Degradation of lambda-carrageenan by Pseudoalteromonas carrageenovora lambda carrageenase: a new family of glycoside hydrolases unrelated to kappa- and iota carrageenases. AB - Carrageenans are sulfated galactans found in the cell walls of red seaweeds. They are classified according to the number and the position of sulfate ester groups. lambda-Carrageenan is the most sulfated carrageenan and carries at least three sulfates per disaccharide unit. The sole known depolymerizing enzyme of lambda carrageenan, the lambda-carrageenase from Pseudoalteromonas carrageenovora, has been purified, cloned and sequenced. Sequence analyses have revealed that the lambda-carrageenase, referred to as CglA, is the first member of a new family of GHs (glycoside hydrolases), which is unrelated to families GH16, that contains kappa-carrageenases, and GH82, that contains iota-carrageenases. This large enzyme (105 kDa) features a low-complexity region, suggesting the presence of a linker connecting at least two independent modules. The N-terminal region is predicted to fold as a beta-propeller. The main degradation products have been purified and characterized as neo-lambda-carratetraose [DP (degree of polymerization) 4] and neo-lambda-carrahexaose (DP6), indicating that CglA hydrolyses the beta-(1-->4) linkage of lambda-carrageenan. LC-MALLS (liquid chromatography-multi-angle laser light scattering) and (1)H-NMR monitoring of the enzymatic degradation of lambda-carrageenan indicate that CglA proceeds according to an endolytic mode of action and a mechanism of inversion of the anomeric configuration. Using 2-aminoacridone-labelled neo-lambda-carrabiose oligosaccharides, in the present study we demonstrate that the active site of CglA comprises at least 8 subsites (-4 to +4) and that a DP6 oligosaccharide binds in the subsites -4 to +2 and can be hydrolysed into DP4 and DP2. PMID- 17269935 TI - Probing the molecular determinants of aniline dioxygenase substrate specificity by saturation mutagenesis. AB - Aniline dioxygenase is a multicomponent Rieske nonheme-iron dioxygenase enzyme isolated from Acinetobacter sp. strain YAA. Saturation mutagenesis of the substrate-binding pocket residues, which were identified using a homology model of the alpha subunit of the terminal dioxygenase (AtdA3), was used to probe the molecular determinants of AtdA substrate specificity. The V205A mutation widened the substrate specificity of aniline dioxygenase to include 2-isopropylaniline, for which the wild-type enzyme has no activity. The V205A mutation also made 2 isopropylaniline a better substrate for the enzyme than 2,4-dimethylaniline, a native substrate of the wild-type enzyme. The I248L mutation improved the activity of aniline dioxygenase against aniline and 2,4-dimethylaniline approximately 1.7-fold and 2.1-fold, respectively. Thus, it is shown that the alpha subunit of the terminal dioxygenase indeed plays a part in the substrate specificity as well as the activity of aniline dioxygenase. Interestingly, the equivalent residues of V205 and I248 have not been previously reported to influence the substrate specificity of other Rieske dioxygenases. These results should facilitate future engineering of the enzyme for bioremediation and industrial applications. PMID- 17269936 TI - Polymorphisms in the CTLA-4 gene and inhibitor development in patients with severe hemophilia A. PMID- 17269938 TI - Deficiency of alpha2-antiplasmin does not affect murine adipose tissue development. PMID- 17269937 TI - Lentivirus-mediated platelet-derived factor VIII gene therapy in murine haemophilia A. AB - BACKGROUND: Previous studies from our laboratory have demonstrated that lineage targeted synthesis of factor VIII (FVIII) under the direction of the platelet specific integrin alphaIIb gene promoter (2bF8) can correct the murine haemophilia A phenotype even in the presence of high titer inhibitory antibodies in a transgenic mouse model. OBJECTIVE: In this study, we assessed the efficacy of using a genetic therapy approach to correct haemophilia A in FVIII-deficient (FVIII(null)) mice by transplantation of bone marrow (BM) transduced with a lentivirus (LV)-based gene transfer cassette encoding 2bF8. RESULTS: Functional FVIII activity (FVIII:C) was detected in platelet lysates from treated mice and the levels were similar to 2bF8 heterozygous transgenic mice. Mice transplanted with 2bF8 LV-transduced BM survived tail clipping and we did not detected inhibitory or non-inhibitory FVIII antibodies over the period of this study (11 months). Furthermore, BM transferred from the primary transplant recipients into FVIII(null) secondary recipients demonstrated sustained platelet-FVIII expression leading to correction of the haemophilia A phenotype showing that gene transfer occurred within long-term repopulating haematopoietic stem cells. CONCLUSIONS: These results demonstrate that ectopic expression of FVIII in platelets by lentivirus-mediated bone marrow transduction/transplantation may be a promising strategy for gene therapy of haemophilia A in humans. PMID- 17269939 TI - Molecular characterization and subcellular localization of Tyr478del: a pathogenic in-frame deletion in coagulation factor V. PMID- 17269940 TI - Efficacy and safety of recombinant factor VIIa in the treatment of bleeding episodes in patients with aplastic anemia. PMID- 17269941 TI - More on: the 'ART' behind the clot: solving the mystery. PMID- 17269943 TI - Lost and found horizons: the quest to create healthy learning climates. PMID- 17269944 TI - Assessment of a matched-pair instrument to examine doctor-patient communication skills in practising doctors. AB - OBJECTIVES: To develop and psychometrically assess the feasibility, reliability and validity of an assessment tool in which both doctor and patient perceptions of the communication that occurred in a single office visit are captured. METHODS: Two 19-item (5-point scale) questionnaires, with parallel content, were developed for doctor and patient completion following a visit. Both process and content were queried. Family doctors and specialists across Canada were recruited to provide data from 25 visits. We assessed feasibility by examining recruitment and percentages of people 'unable to assess' each item. Evidence for validity was examined through exploratory factor analysis, the correlations between doctor and patient data and linear regression. Reliability was assessed through internal consistency reliability and generalisability coefficient analyses. RESULTS: Data from 1845 doctor-patient dyads (91 doctors) showed similarly high ratings (> 4/5) for both doctors and patients, with few unable-to-assess items. There were low correlations between items and questionnaires. The principle components analysis indicated 2 factors, process and content, accounting for 52% and 7% of the doctor variance and 60% and 6% of the patient variance, respectively. The linear regression showed that only gender accounted for any of the variance in ratings. Cronbach's alphas for both doctor and patient questionnaires were > or = 0.96. The G analysis provided a G = 0.98 and 0.40 (standard errors of 0.003 and 0.02) for doctors and patients, respectively. CONCLUSIONS: The data suggest this is a feasible tool with which to assess communication skills and that there is evidence for its validity and reliability. PMID- 17269945 TI - Promoting lay participation in medical school curriculum development: lay and faculty perceptions. AB - INTRODUCTION: Although medical schools are encouraged to increase community involvement in medical student training, little information is available about how best to achieve this. While lay community members are not medical 'experts', as recipients of health care services they have vested interests in ensuring optimal health care for themselves and their families. This study explored and compared lay and faculty perceptions around lay participation in medical curriculum development at one medical school. METHODS: Thirty-two lay volunteers responded to a newspaper advertisement. Seventeen volunteers subsequently participated in 1 of 3 lay focus group discussions. Ten academic staff attended a separate faculty focus group. The 3 lay participants and 1 faculty focus group transcripts were analysed independently and then compared using an iterative process of theme identification and hypothesis testing. RESULTS: Contrasting perspectives of lay and faculty participants were evident in all aspects of the focus group discussions. For lay participants, some sharing of curriculum ownership by medical experts with the lay community was regarded as necessary to create environments that legitimised lay status and acknowledged the importance of lay perspectives. Faculty participants presumed ownership of curriculum development, giving rise to a paternalistic approach to controlling resources and an assumed responsibility (as experts) to define the parameters of lay participation. CONCLUSIONS: The results of this study have highlighted many of the challenges inherent in the process of lay participation in medical curriculum development. A model is proposed to facilitate and promote lay participation in medical curriculum development. PMID- 17269946 TI - Much variety and little evidence: a description of guidelines for doctor-patient communication. AB - AIM: To explore the quality of the content of communication skills training programmes, we analysed and assessed guidelines for doctor-patient communication used in communication programmes for general practitioner (GP) trainees. METHOD: Guidelines for doctor-patient communication were extracted from educational materials supplied by the 8 Dutch university centres for vocational training in general practice. Four themes guided the analysis of the guidelines: content, type of contact, format and structure and status. The quality of the guidelines was assessed with the Appraisal of Guidelines Research and Evaluation (AGREE) instrument, a validated measurement instrument for guideline quality. RESULTS: We identified 18 guidelines. Guideline content covered 64-100% of the GP qualification requirements. General consultations and specific situations were the subject of 9 guidelines each. Format and structure differed between guidelines. Guideline use seemed not to be obligatory. AGREE scores were low. CONCLUSIONS: Guidelines for doctor-patient communication are difficult to identify in materials of GP training courses. Guideline quality is low; guidelines are little evidence-based and little attention has been paid to applicability and involvement of users. GP qualification requirements are only partly covered. Guidelines differed substantially without clarity about the reasons behind different choices. Guideline status was low. RECOMMENDATIONS: When studying the factors that influence training effect, the quality of training content should be considered as well as teaching methods. Communication skills training programmes should be based on evidence-based guidelines that have been developed according to similar standards as for medical technical guidelines. PMID- 17269947 TI - Medical students' attitudes toward patient-centred care: a longitudinal survey. AB - PURPOSE: Patient-centredness should be at the heart of medical education. This longitudinal study aimed to assess possible attitude changes towards patient centredness in a medical students' cohort as they progressed through the clinical curriculum. It also investigated the possible impact of socio-demographic factors on students' attitudes. METHODS: The same student cohort was tested on 2 occasions: during their initial exposure to clinical curricula (year 4) and after 2 years, at the end of the clerkship (year 6). Students completed a questionnaire including demographics and the 18-item Patient-Practitioner Orientation Scale (PPOS). PPOS differentiates between patient-centred versus doctor-centred or disease-centred orientation, measuring attitudes along 2 dimensions: 'sharing' and 'caring'. RESULTS: A total of 483 fully completed questionnaires was returned (response rate 83%). The cohort's attitudes were significantly more doctor centred at the end of their studies compared to the beginning of their clinical curricula (P < 0.001). However, regarding the caring part of their relationship with patients, they maintained a satisfactory level of patient-centredness. Concerning sharing information, female students were significantly more patient centred at year 4, with their mean score decreasing at the end of their clerkship. Furthermore, among only female students, having a looser relationship with religion was associated with more patient-centred attitudes. CONCLUSIONS: Increased authoritarianism in graduating students' attitudes emphasises clearly the need for future research and redesigning communication curricula. Furthermore, the influence of gender and relationship with religion on attitudes towards the doctor-patient relationship should be explored further, in order to eliminate disparities in the provision of patient-centred medical care. PMID- 17269948 TI - Impact of a new curriculum on medical students' interpersonal and interviewing skills. AB - OBJECTIVES: In 1998 we reported on the rise and fall of medical student communication skills during the 4 years of medical school. Since then, the University of Connecticut School of Medicine has completed a major curriculum renewal project with an emphasis on early clinical work, lifelong learning and more ambulatory training. The goals of this study were to compare students' interviewing and interpersonal skills in standardised patient (SP) assessments in the old and new curricula and to assess the success of the new curriculum in preventing a decline in student skills in this domain. METHODS: The clinical skills of 202 students were measured longitudinally during encounters with SPs in each of their 4 years of medical school. Students in this study and the earlier study were evaluated using the Arizona Clinical Interviewing Rating (ACIR) Scale. RESULTS: Compared with students from the previous curriculum, students on the new curriculum in this study showed an improvement in ACIR scores. Year 1 mean ACIR scores (1 = poor to 5 = excellent) were, respectively, 3.6 for the old curriculum cohort and 4.0 for the new curriculum group. In Year 4 the mean score for the old curriculum cohort was 3.7 and that for the new curriculum group was 3.8. Students on the new curriculum still showed a decline in ACIR scores from Years 1 to 4, but it was not as severe a decline as it had been previously. CONCLUSIONS: Pre clinical medical students perform better on measures of interpersonal communication than their clinical counterparts. The students who participated in the new curriculum demonstrated an earlier acquisition of and a less steep decline in interviewing and interpersonal skills during the course of medical school. PMID- 17269949 TI - Teaching brief motivational interviewing to Year three medical students. AB - OBJECTIVES: In 2005, the authors developed and tested a curriculum to teach Year 3 Yale University medical students a behaviour change counselling approach called 'brief motivational interviewing' (BMI). Brief motivational interviewing is a patient-centred approach designed to promote changes in patient behaviour within the time constraints imposed by a busy medical practice. METHODS: Standardised patients/instructors delivered the curriculum within a single 2-hour training episode using a teaching acronym called 'CHANGE' to promote the students' learning. The authors used a pretest, post-test and 4-week follow-up design to assess students' BMI skills (as measured by the Helpful Response Questionnaire), knowledge and attitudes toward the approach. RESULTS: Students successfully increased their use of BMI-consistent behaviours, primarily by increasing the frequency and depth of their reflections and by reducing the frequency with which they incorporated communication roadblocks and closed questions into their responses (all P-values < or = 0.05). Students also showed increases in BMI knowledge, interest in the approach, confidence in their ability to use BMI, and commitment to incorporating BMI skills into their future medical practice (all P values < or = 0.05). CONCLUSIONS: The findings suggest that Year 3 medical students can learn basic BMI skills and knowledge and develop positive attitudes toward the approach within a relatively short period of time. The authors discuss the study's limitations and future directions for teaching students BMI. PMID- 17269950 TI - Surgical e-learning: validation of multimedia web-based lectures. AB - BACKGROUND: Distance learning has been advocated increasingly as a modern efficient method of teaching surgery. Efficiency of knowledge transfer and validity of web-based courses have not been subjected to rigorous study to date. METHODS: An entirely web-based surgical 5-week lecture course was designed. Fifty per cent of the lectures were prepared as HTML slides with voice-over while the other group was presented in the text-only form. Only written material presented was examined. The lectures were presented via an educational web module. The lecture series was balanced specifically to reduce the pre-existent knowledge bias. Web usage was estimated utilising surrogates, including the number of hits as well as log-on timing. Face validity was assessed by a standardised questionnaire. RESULTS: Eighty-eight students took part in the lecture series and subsequent examination and questionnaire. Median multiple choice questionnaire (MCQ) marks were significantly higher in the aural lecture-derived stems versus the non-aural (P = 0.012, Mann-Whitney U-test). There was widespread approval of web-based learning as an adjunct to conventional teaching. Usage rates were augmented significantly in the final week when compared to the previous 4 weeks (mean total hits weeks 1-4 +/- SEM: 100.9 +/- 9.7 and mean total hits week 5: 152.1 +/- 13.1; P < 0.001, Kruskal-Wallis). However, total hits did not correlate with overall examination results (r(2) = 0.16). The aural lectures demonstrated higher face validity than the non-aural for content and presentation (P < 0.05, Kruskal-Wallis). CONCLUSIONS: The addition of aural files to the novel web-based lecture series is face valid and results in significantly increased examination performance. PMID- 17269951 TI - Target-focused medical emergency team training using a human patient simulator: effects on behaviour and attitude. AB - CONTEXT: Full-scale simulation training is an accepted learning method for gaining behavioural skills in team-centred domains such as aviation, the nuclear power industry and, recently, medicine. In this study we evaluated the effects of a simulator team training method based on targets and known principles in cognitive psychology. METHODS: This method was developed and adapted for a medical emergency team. In particular, we created a trauma team course for novices, and allowed 15 students to practise team skills in 5 full-scale scenarios. Students' team behaviour was video-recorded and students' attitude towards safe teamwork was assessed using a questionnaire before and after team practice. RESULTS: Nine of 10 observed team skills improved significantly in response to practice, in parallel with a global rating of team skills. In contrast, no change in attitude toward safe teamwork was registered. CONCLUSION: The use of team skills in 5 scenarios in a full-scale patient simulator environment implementing a training method based on targets and known principles in cognitive psychology improved individual team skills but had no immediate effect on attitude toward safe patient care. PMID- 17269952 TI - How video cases should be used as authentic stimuli in problem-based medical education. AB - PURPOSE: To examine problem-based learning (PBL) students' views on the added value of video cases compared to text-based cases in the pre-clinical phase of undergraduate medical education and on the conditions for productive use of video in tutorial group discussions. METHOD: Participants were 2nd-year students who had completed a PBL programme featuring video cases. Three groups of 6-8 randomly selected students participated in focus-group interviews guided by a moderator using a 'questioning route'. The interviews were audiotaped, transcribed and analysed. The summary reports were approved by the students. RESULTS: According to the students, the video cases enabled them to create realistic mental pictures of disorders, provided integrated pictures of patients as people, which challenged them to elaborate the cases seriously and were more memorable than text-based cases. Cases that students perceived as fostering the productive use of video were neither too directive nor too complete, tailored to students' prior knowledge, short, varied in design and complementary to other materials. The cases should be viewed in a structured, purposeful manner, with cues, instructions and prompts to focus attention on essential issues. CONCLUSION: The video cases were generally perceived as a valuable stimulus for group discussions in PBL. However, productive use depended on specific conditions. Many of the advantages and conditions mentioned are supported by earlier non-empirical claims in the literature or can be explained by theory and empirical studies on symbol systems. Future observational studies should address the effects of specific attributes of video as a medium. PMID- 17269953 TI - Effectiveness of using blended learning strategies for teaching and learning human anatomy. AB - OBJECTIVES: This study aimed to implement innovative teaching methods--blended learning strategies--that include the use of new information technologies in the teaching of human anatomy and to analyse both the impact of these strategies on academic performance, and the degree of user satisfaction. METHODS: The study was carried out among students in Year 1 of the biology degree curriculum (human biology profile) at Pompeu Fabra University, Barcelona. Two groups of students were tested on knowledge of the anatomy of the locomotor system and results compared between groups. Blended learning strategies were employed in 1 group (BL group, n = 69); the other (TT group; n = 65) received traditional teaching aided by complementary material that could be accessed on the Internet. Both groups were evaluated using the same types of examination. RESULTS: The average marks presented statistically significant differences (BL 6.3 versus TT 5.0; P < 0.0001). The percentage pass rate for the subject in the first call was higher in the BL group (87.9% versus 71.4%; P = 0.02), reflecting a lower incidence of students who failed to sit the examination (BL 4.3% versus TT 13.8%; P = 0.05). There were no differences regarding overall satisfaction with the teaching received. CONCLUSIONS: Blended learning was more effective than traditional teaching for teaching human anatomy. PMID- 17269954 TI - Expert consensus on contamination in educational trials elicited by a Delphi exercise. AB - CONTEXT: Contamination occurs when participants in the control arm of a trial receive an intervention that was intended for the intervention arm. Contamination tends to bias estimates of effectiveness towards no effect, and to reduce a trial's power to detect significant differences in outcomes. This is often assumed to be a problem in trials of educational interventions because of the transferability of verbal and experiential approaches. Cluster randomisation and other trial designs and analyses commonly used to reduce contamination can themselves cause bias or reduce statistical power. METHODS: We conducted a Delphi exercise to elicit experts' opinions about factors more or less likely to lead to contamination, and to rank methods of avoiding contamination when planning trials of educational interventions. RESULTS: Trials in settings with social, geographical or professional overlaps of respondents were considered to be at highest risk of contamination. Interventions that were complex and aimed to change behaviour were thought less likely to contaminate trials than simple interventions or those aimed at increasing knowledge. DISCUSSION: Although the issue of contamination requires detailed consideration of the nature of the intervention and academic judgement, this study adds to the literature on factors affecting contamination in educational studies and its findings will assist researchers in deciding whether they need to choose a cluster randomised trial design. The classification of studies and their likelihood of contamination suggest that complex interventions, also known to have greatest impact on behavioural change, have advantages in minimising contamination. Further work is required to see whether the additional costs of clustered studies are offset by the greater costs of complex interventions, while the aim of the study remains central to any choice of trial design. PMID- 17269955 TI - Lessons learned from complementary and integrative medicine curriculum change in a medical school. AB - OBJECTIVES: This paper describes a pilot study that examined lessons learned from the introduction of complementary and alternative medicine (CAM) elements into a medical school curriculum. METHODS: A qualitative approach was selected as a first step in evaluating the phenomenological experience of introducing the CAM Educational Project in 2000-05. In 2005, semi-structured interviews were conducted with faculty staff and graduating students who had participated in all 4 years of the CAM Project. Qualitative content was analysed focusing on linguistic data and contextual meaning. RESULTS: The overall response to the integration of CAM curricular elements into the medical school curriculum was positive among all faculty and graduating medical students. Participant experiences were often dependent on the perceived rigour of alternative approaches to a presenting patient problem, along with the importance attributed to openness to patient perspectives as part of evidence-based practices. There was an appreciation of the importance of developing increased awareness and utilisation of CAM in medical practice, as well as a recognition of resistance by some medical school faculty to CAM approaches. CONCLUSIONS: This evaluation of a specific CAM educational project suggests potentially transferable findings to other medical schools. Integrating CAM into the medical school curriculum requires a dedicated team if it is to result in a significant change. This change requires that CAM practices are visible to both students and faculty, that there is a co-operative climate, accessible resources, and institutional support, and that CAM content is embedded into the existing curriculum. All these factors combined can lead to sustainable integration of CAM content issues into the medical school curriculum. PMID- 17269956 TI - Does teaching style matter? A randomised trial of group discussion versus lectures in orthopaedic undergraduate teaching. AB - OBJECTIVES: Educational theory suggests that lectures may not be the best way to impart knowledge to students. The aim of this study was to compare the use of didactic lectures with that of interactive discussion sessions in undergraduate teaching of orthopaedics and trauma. METHODS: A total of 77 medical students were assessed in 3 consecutive cohorts. The students were randomised into 2 groups. The first group received a series of 12 formal lectures. The second group covered the same topics in 12 group-discussion sessions with self-directed learning. RESULTS: The students in the interactive discussion group rated the presentation of their teaching more highly than those in the lecture group (P = 0.003). However, there was no difference in their rating of the content of the sessions. The students in the discussion group also performed better on their end-of placement written test (P = 0.025). CONCLUSIONS: We found that interactive teaching styles are more popular than didactic lectures in undergraduate orthopaedic and trauma teaching. We also found some evidence that knowledge retention is better following an interactive teaching style. PMID- 17269957 TI - Nephrin in medical education and other stories. PMID- 17269958 TI - Peer-led medical student tutorials using the cardiac simulator 'Harvey'. PMID- 17269959 TI - Bone healing at implants with a fluoride-modified surface: an experimental study in dogs. AB - OBJECTIVES: The aim of the present experiment was to study early stages of osseointegration to implants with a fluoride-modified surface. MATERIAL AND METHODS: Six mongrel dogs, about 1-year old, were used. All mandibular premolars and the first mandibular molars were extracted. Three months later, mucoperiosteal flaps were elevated in one side of the mandible and six sites were identified for implant placement. The control implants (MicroThread) had a TiOblast surface, while the test implants (OsseoSpeed) had a fluoride-modified TiOblast surface. Both types of implants had a similar geometry, a diameter of 3.5 mm and were 8 mm long. Following installation, cover screws were placed and the flaps were adjusted and sutured to cover all implants. Four weeks after the first implant surgery, the installation procedure was repeated in the opposite side of the mandible. Two weeks later, biopsies were obtained and prepared for histological analysis. The void that occurred between the cut bone wall of the recipient site and the macro-threads of the implant immediately following implant installation was used to study early bone formation. RESULTS: It was demonstrated that the amount of new bone that formed in the voids within the first 2 weeks of healing was larger at fluoride-modified implants (test) than at TiOblast (control) implants. It was further observed that the amount of bone-to-implant contact that had been established after 2 weeks in the macro-threaded portion of the implant was significantly larger at the test implants than at the controls. CONCLUSION: It is suggested that the fluoride-modified implant surface promotes osseointegration in the early phase of healing following implant installation. PMID- 17269961 TI - Alopecia areata. AB - Alopecia areata (AA) is a nonscarring, autoimmune, inflammatory, hair loss on the scalp, and/or body. Etiology and pathogenesis are still unknown. The most common site affected is the scalp. Histopathology is characterized by an increased number of the catagen and telogen follicles, the presence of inflammatory lymphocytic infiltrate in the peribulbar region ("swarm of bees"). Corticosteroids are the most popular drugs for the treatment of this disease. Etiologic and pathogenic mechanisms, as well as other current treatments available will be discussed in this article. PMID- 17269962 TI - Clinical manifestations and classification of Old World cutaneous leishmaniasis. PMID- 17269963 TI - Clinicopathologic challenge. Childhood granulomatous peri-orificial dermatitis with extra-facial lesions. PMID- 17269964 TI - Cross-reactivity of Anisakis simplex: possible role of Ani s 2 and Ani s 3. AB - BACKGROUND: Anisakis simplex is a fish parasite that can cause allergy in humans. The multiple cross-reactivities of this nematode make diagnostic tests for allergy unreliable, because of frequent false-positive results. To date, only four allergens of A. simplex have been characterized, but their role in cross reactivity is largely unknown. METHODS: We performed an amino acid sequence homology analysis, according to the Food and Agriculture Organization/World Health Organization (FAO/WHO) criteria, to identify allergens likely to be cross reactive with Ani s 2 (paramyosin) and Ani s 3 (tropomyosin) of A. simplex. Next, within segments shared by Ani s 2 or Ani s 3 and homologous proteins, we searched for the occurrence of binding motifs of human leukocyte antigen (HLA) alleles (DRB1*1502, DQB1*0601, or DRB1*0404) known to be genetic risk factors for the development of allergy to A. simplex. RESULTS: We identified a number of proteins belonging to various organisms, which are significantly similar to (and therefore are likely to cross-react with) Ani s 2 and Ani s 3. The presence of binding motifs of HLA DRB1*0404 in Ani s 2, Ani s 3, and homolog proteins also supports our hypothesis. CONCLUSIONS: Our results provide a possible molecular explanation of some cross-reactivities reported for A. simplex, and suggest additional ones. PMID- 17269965 TI - Plica polonica in association with pediculosis capitis and scabies - a case report. AB - Plica polonica is a rare disorder of hair in which groups of hair shafts become irreversibly entangled, forming a matted, malodorous and encrusted, sticky, moist mass. Various predisposing factors are known to cause this condition. We report one such case associated with pediculosis capitis and scabies. PMID- 17269966 TI - Cytochrome P450 polymorphisms in patients with Behcet's disease. AB - OBJECTIVES: Although the etiopathogenesis of Behcet's disease (BD) remains unknown, increased neutrophil functions such as chemotaxis, phagocytosis and excessive production of reactive oxygen species, including superoxide anion, may be responsible for the oxidative tissue damage observed in BD. Cytochrome P-450 are a multigene family of enzymes involved in the detoxification and occasional activation of a wide variety of chemicals. Our aim was to investigate CYP2C9 and CYP2C19 polymorphisms in patients with BD. METHODS: Sixty-two subjects with BD and 107 healthy control subjects were enrolled in the study. Polymorphisms of CYP2C9 and CYP2C19 were performed by real-time PCR with a LightCycler instrument. We researched associations between CYP polymorphisms and BD. RESULTS: The frequencies of wild-type and heterozygous CYP2C19*2 genotypes were 66.1% and 33.9% in the patients and 83.2% and 16.8% in the controls, respectively. There was a 2.53-fold increased risk of Behcet's disease in individuals with the CYP2C19*2 heterozygous genotype (OR = 2.53; 95% CI, 1.22-5.25) when compared with the control group. But the CYP2C9*2, CYP2C9*3 and CYP2C19*3 gene polymorphisms were not related to an increased risk of developing BD. CONCLUSIONS: We observed that patients with BD presented with a higher prevalence of the heterozygous CYP2C19*2 genotype. Hereditary deficiencies of this enzyme activity may lead to an imbalance between pro- and antioxidant systems, resulting in the formation of excessive reactive oxygen species. PMID- 17269967 TI - Caffeine consumption and methotrexate dosing requirement in psoriasis and psoriatic arthritis. AB - BACKGROUND: Recent animal and human studies have suggested that the therapeutic benefit of methotrexate in the treatment of rheumatoid arthritis may be substantially reduced in patients who are concomitantly consuming caffeine. Here, we aimed to investigate the effect of caffeine consumption on the methotrexate dosing requirements in patients with psoriasis and psoriatic arthritis. METHODS: One hundred and fifty patients with diagnoses of psoriasis or psoriatic arthritis were surveyed for their current weekly methotrexate dosage and their usual daily consumption of caffeine. RESULTS: Seventy-five of the patients given the survey responded; of these, 11 were eliminated because they did not report their methotrexate dosage or were no longer taking methotrexate. Of the remaining 64 patients, no correlation was found between the methotrexate dosage needed for disease maintenance and the amount of caffeine consumed. CONCLUSIONS: Our findings suggest that caffeine does not affect methotrexate dosage requirements in patients with psoriasis and psoriatic arthritis. These results do not rule out an effect of caffeine in other inflammatory diseases treated with methotrexate. PMID- 17269968 TI - Early-stage mycosis fungoides, parapsoriasis en plaque, and pregnancy. AB - BACKGROUND: Non-Hodgkin's lymphoma (NHL) coincident with pregnancy is rare, and the literature regarding mycosis fungoides (MF), the most common primary cutaneous NHL, and pregnancy is strikingly sparse. The effect of pregnancy on MF, or on parapsoriasis en plaque (PPP), and the effect of these diseases on pregnancy, are still unknown. OBJECTIVE: To study the effect of pregnancy on MF and PPP and the impact of these diseases on pregnancy. METHODS: The files of the MF and PPP patients seen during the past 12 years in our department were reviewed to search for patients who had been pregnant during the course of their disease. RESULTS: Nine women who met the study criteria were identified, seven with early stage MF and two with PPP. A total of 12 pregnancies was recorded: nine in patients with MF and three in patients with PPP. In none of the patients was there any indication that pregnancy changed the course of MF or PPP. Of the 12 pregnancies, 11 were normal; one was naturally aborted. Two of the patients were treated with topical steroids during pregnancy. One patient was treated with narrow-band ultraviolet-B combined with topical steroids. The rest preferred to avoid any therapy. CONCLUSIONS: Pregnancy appeared to have no impact on the course of early MF or PPP, and no adverse effect was noted on pregnancy. Further studies are needed to clarify the interplay between pregnancy and MF or PPP. PMID- 17269969 TI - 99mTc-MIBI imaging of cutaneous AIDS-associated Kaposi's sarcoma. AB - BACKGROUND: Kapoksi's sarcoma (KS) is a common neoplasm complicating acquired immunodeficiency syndrome (AIDS). Skin, mucus membranes, lymph nodes, gastrointestinal tract and lungs may be involved. Kaposi's sarcoma has been demonstrated by scintigraphy, and a (99m)Tc-hexakis-2-methoxy isobutyl isonitrile (MIBI) scan can demonstrate lymphoma and tumors of the brain, nasopharynx, thyroid, parathyroid, lung, breast and kidney. It may also be useful for detecting and delineating the extent of KS. The objective of this study was to determine the efficacy of (99m)Tc-MIBI scanning to demonstrate cutaneous AIDS associated KS, lymphedema and lymphadenopathy in the extremities. METHODS: Whole body (99m)Tc-MIBI scans were obtained on 40 patients with AIDS-associated KS. Abnormal uptake of (99m)Tc-MIBI in the skin, subcutaneous soft tissues and lymph nodes was compared with the clinical assessment. RESULTS: The (99m)Tc-MIBI uptake was noted in the cutaneous/subcutaneous KS of the extremities with a sensitivity of 73.53%, a specificity of 96.91% and an accuracy of 91.31%. Abnormal lymph nodes and lymphedema were detected in more patients on (99m)Tc-MIBI scans (33 and 18 patients) than clinical assessment (10 and 12 patients), respectively. Lymphedema of the lower extremity was found in four of 17 patients without any palpable or abnormal lymph node uptake of (99m)Tc-MIBI in the inguinal regions. Follow-up (99m)Tc-MIBI scans after treatment showed no uptake in the skin lesions and decreased uptake in the lymph nodes corresponding to complete clearing on clinical assessment. CONCLUSIONS: (99m)Tc-MIBI imaging provides additional information on the extent of lymph node involvement and more precise staging and therapeutic planning. It may be useful as a predictive test or follow up of response of cutaneous KS to treatment. PMID- 17269970 TI - Caspase-9 expression is increased in endothelial cells of active Behcet's disease patients. AB - BACKGROUND: Behcet's disease is a multisystem disease of unknown etiology. Caspase-9 is responsible for initiating the caspase activation cascade during apoptosis. The aim of this study was to examine caspase-9 expression in both endothelial and perivascular infiltrates of patients with active Behcet's disease. METHODS: Fifteen patients with active Behcet's disease, attending the First Dermatology Department, Ankara Numune Hospital, Ankara, Turkey between June 2003 and December 2005, were included in the study. Oral biopsy specimens from nine healthy volunteers were taken as the healthy control group, and skin biopsies from 18 psoriasis patients were used as the inflammatory control group. The specimens were examined with caspase-9 primary antibody. Statistical analyses were performed using SPSS 11.5. RESULTS: The mean caspase-9-positive endothelial cell counts were 7.17 +/- 2.45 in active Behcet's disease, 4.81 +/- 0.76 in healthy controls, and 4.35 +/- 1.34 in inflammatory controls. The difference between Behcet's disease and healthy controls was statistically significant, with increased endothelial staining in active Behcet's disease (P = 0.049). The difference between Behcet's disease and inflammatory controls was also statistically significant; the rate of staining was higher in Behcet's disease (P = 0.006). The mean caspase-9-positive dermal perivascular cell counts were 5.15 +/- 2.32 in Behcet's disease, 3.32 +/- 0.82 in healthy controls, and 5.54 +/- 4.95 in inflammatory controls. These values did not show any statistically significant difference (P = 0.407). CONCLUSION: Endothelial cells are one of the key cells in Behcet's disease, and our findings support the role of endothelial cells in the etiopathogenesis of Behcet's disease. PMID- 17269971 TI - Epidemiological data and molecular characterization (mtDNA) of Sporothrix schenckii in 13 cases from Mexico. AB - BACKGROUND: Sporotrichosis is an endemic mycosis in Mexico and Central America. OBJECTIVES: To present epidemiological data and characterize molecular subtypes of 13 strains of Sporothrix schenckii, and to correlate clinical and epidemiologic presentation with subtypes. METHODOLOGY: Thirteen Mexican cases of sporotrichosis were identified, and mitochondrial DNA (mtDNA) from clinical isolates of S. schenckii were analyzed using RFLP Hae III. Molecular types 2, 3, 14, 28, and 29 were observed. RESULTS: Clinical presentations and molecular types were consistent with established epidemiologic patterns for S. schenckii in this region. CONCLUSIONS: This investigation provides further evidence of the strong regional specificity of molecular types of this organism. PMID- 17269972 TI - Lobomycosis in Venezuela. AB - Lobomycosis is a chronic dermal infection that presents a wide spectrum of clinical- dermatological manifestations, mainly characterized by the development of keloid lesions as well as nodular, verrucoid and sometimes ulcerous forms. The etiological agent at an international level, according to the consensus nomenclature, has been called Loboa loboi, even though recently it has been accommodated as Lacazia loboi. The present review extensively covers the clinical epidemiological aspects as well as the most outstanding historical aspects, including the Venezuelan experience and the presentation of two new cases, which substantiate the Amazon basin as an endemic area for the disease. PMID- 17269973 TI - Eruptive dermatosis papulosa nigra as a possible sign of internal malignancy. AB - A 42-year-old black woman presented with dermatosis papulosa nigra lesions of 15 years' duration. Coincident with the diagnosis of symptomatic iron-deficiency anemia about 1 year ago, she reported an "explosion" in number and size of the lesions progressing from her face to her trunk and arms. Physical examination revealed numerous 1-5-mm, black, smooth, verrucous papules predominantly on the forehead, malar region of the face, neck, and upper trunk (Figs 1 and 2). The lesions on the back were situated in a "Christmas tree" pattern and included two 1-cm papules. She had multiple 1-mm papules on the upper arms. A biopsy confirmed the diagnosis of dermatosis papulosa nigra, showing parakeratosis, acanthosis, hyperpigmentation, thick interwoven tracts of epithelial cells, and horn cysts. Given the eruptive nature of her disease, the possibility of an underlying malignancy was entertained. Six weeks later, she went to the emergency room for severe weakness; a colonoscopy revealed an ascending colon adenocarcinoma with a negative metastatic work-up. PMID- 17269974 TI - Cervical cancer metastasis to the scalp presenting as alopecia neoplastica. AB - A 45-year-old Japanese woman was diagnosed in 1996 with squamous cell cancer of the cervix following an abnormal Papanicolaou smear and subsequent diagnostic conization. She underwent total abdominal hysterectomy with pelvic lymphadenectomy and was found to have poorly differentiated squamous cell carcinoma, International Federation of Gynecology and Obstetrics (FIGO) stage IB1. She remained asymptomatic until 2003 when she presented with obstructive uropathy with acute renal failure and hydronephrosis, suspected to be from the recurrence of cervical cancer. This was confirmed when computerized tomography (CT)-guided lymph node biopsy showed squamous cell carcinoma of the para-aortic lymph nodes histologically consistent with the cervical primary. In addition, there was evidence of lumbar spine metastasis by positron emission tomography (PET) and bone scans. She received several courses of chemotherapy with cisplatin and 5-fluorouracil (5FU), as well as radiation therapy. In July 2004, she was hospitalized for acute renal failure, nausea, vomiting, and anorexia. CT of the abdomen identified widespread metastases in the liver, pancreatic head, and lumbar spine. During this hospitalization, she complained of severe scalp tenderness and patchy hair loss first noticed 3 days prior to presentation. On examination of her scalp, two patches of alopecia were observed (Fig. 1). In the largest patch, there was a 5 x 2.5-cm, tender, erythematous plaque with atrophy. In the smaller patch, there was a 2 x 1.5-cm, erythematous, scaly plaque. A punch biopsy of the larger patch revealed atypical epithelial cells in nests with intravascular involvement and diminished numbers of focally miniaturized hair follicles (Fig. 2a). The scalp specimen was histologically identical with biopsy specimens of the cervical primary (Fig. 2b). There was also seborrheic dermatitis, with thick greasy scale, noted on the scalp, which resolved with fluocinolone solution. The patient decided against further treatment for her advanced cervical cancer but did accept hydromorphone for pain. She died 3 months after admission. PMID- 17269975 TI - Pili Canaliculi: clinical and microscopic investigation of the first Brazilian family. PMID- 17269976 TI - Scurvy in a 10-month-old boy. AB - We report a 10-month-old boy with inflammatory and necrotic gingival lesions, fever, irritability, and pseudoparalysis of the legs. Laboratory examinations revealed moderate anemia and skeletal X-rays showed osteopenia, scorbutic rosary at the costochondral junctions, and "corner sign" on the proximal metaphyses of the femora. The boy had been fed only with diluted cow's milk. He had never taken solid food, vitamin C, or iron complement. Seventy-two hours after starting oral vitamin C supplementation, there was significant improvement in the patient's gingival lesions and general health. The clinical presentation and laboratory and imaging findings, together with the dramatic response to ascorbic acid intake, allowed us to confirm the diagnosis of infantile scurvy. Scurvy, a dietary disease due to the deficient intake of vitamin C, is uncommon in the pediatric population. In an infant who has never received vitamin C, the combination of gingival lesions, pseudoparalysis, and irritability strongly suggests a diagnosis of scurvy. The clinical picture, together with the laboratory data, radiological studies, and therapeutic response to vitamin C administration, confirmed the diagnosis. PMID- 17269977 TI - An unusual presentation of human papillomavirus (HPV) infection in a black epidermodysplasia verruciformis (EV) patient. AB - A 25-year-old black man had a 20-year history of disseminated plaques on his body. Two years before consultation he noticed several tumors on the genitalia. Physical examination revealed generalized, coalescing, hypopigmented plaques with a very defined and keratotic border that resembled actinic porokeratosis. (Fig. 1). Multiple verrucous and moist tumors were observed on the scrotum (Fig. 2). His past medical history was unremarkable, and no family member had the disease. Histology of the body lesions revealed hyperkeratosis with a horny-layer, basket weave appearance, large and clear blue-gray keratinocytes with finely granular cytoplasm and vacuolized nuclei, and abundant keratohyaline granules located in the upper epidermal layer (Fig. 3). Scrotum biopsy showed hyperkeratosis, irregular acanthosis with papillomatosis, and koilocytic figures. The genital lesions were treated with monthly cryotherapy plus surgical excision with complete disappearance of the lesions. A decrease in ultraviolet exposure and daily sun-block were encouraged for epidermodysplasia verruciformis lesions. After genital wart clearance, follow-ups are being scheduled every 4 months, with no new lesions to date. PMID- 17269978 TI - Acro-osteolysis: a complication of Jadassohn-Lewandowsky syndrome. PMID- 17269979 TI - Vesicular pemphigoid with circulating autoantibodies against 230-kDa and 180-kDa proteins, and additional autoantibodies against 97-kDa and 45-kDa proteins. AB - The vesicular variant of bullous pemphigoid is a clinical entity in which the principal type of lesions are multiple small tense vesicles in a symmetric distribution, instead of the classical large, more randomly distributed large bullae. We describe a 62-year-old female who developed a vesicular variant of bullous pemphigoid, with intensely pruritic vesiculopapular eruptions and erythematous irregularly outlined patches confluent on the face, neck, trunk, extremities and oral mucosa. Direct immunofluorescence revealed a linear deposition of IgG and C3 at the basement membrane zone of the skin, and indirect immunofluorescence detected circulating IgG autoantibodies reacting with antigens located on the epidermal side of skin split with 1 M NaCl. Indirect immunogold electron microscopy revealed IgG deposition at the underneath membrane of the basal cells and in the lamina lucida. In addition to the 230-kDa and 180-kDa bullous pemphigoid antigen, immunoblot analysis also demonstrated the presence of IgG antibodies reactive with 97-kDa and 45-kDa protein. Treatment with systemic corticosteroid, minocycline and antihistamines plus topical steroid resulted in moderate improvement. A few vesicles, however, continued to appear intermittently during the past year of treatment. PMID- 17269980 TI - Need for physician monitoring of long-term safety with lasers and intense pulsed light. PMID- 17269981 TI - Botulinum toxin therapy for palmar hyperhidrosis: experience in an Iranian population. PMID- 17269982 TI - Efficacy of 10% silver nitrate solution in the treatment of common warts: a placebo-controlled, randomized, clinical trial. AB - BACKGROUND: Warts are a common skin lesion, especially in children and young adults, caused by human papillomaviruses. So far, there is no definitive therapy for warts and the treatment is modified regularly to obtain the best result with the least discomfort to the patient. The aim of this placebo-controlled clinical trial was to evaluate the clinical efficacy, tolerability, and safety of 10% silver nitrate solution for the treatment of common warts. METHODS: Sixty individuals attending pediatrics and dermatology clinics and health centers in Yasuj, south-west of Iran, were recruited. The patients were divided into two groups: 30 patients received 10% silver nitrate solution (case group) and 30 control patients received black ink (placebo group). Silver nitrate solution was used every other day for 3 weeks. After 3 weeks, the patients were evaluated for healing, and treatment was continued for another 3 weeks if the lesions were still present. RESULTS: Complete regression of lesions was achieved in 19 of the 30 (63.33%) case patients. No significant side-effect was noted in the treated patients apart from temporary brownish discoloration of the skin which resolved 1 week after treatment. CONCLUSION: This study demonstrated that 10% silver nitrate solution can be used effectively for the treatment of warts with no serious complications. PMID- 17269983 TI - Evaluation of oral methotrexate in the treatment of systemic sclerosis. AB - BACKGROUND: Treatment of scleroderma is difficult and currently no treatment can induce complete remission of the disease. OBJECTIVE: To evaluate weekly oral methotrexate in the treatment of Indian patients with systemic sclerosis. METHODS: Thirty-three patients with systemic sclerosis presenting to the department of dermatology (outpatients) who satisfied the inclusion criteria were enrolled into the study. All cases were admitted into the dermatology ward for detailed evaluation. A detailed history and physical examination, including assessment of disease severity by Rodnan skin scoring, was carried out. Baseline investigations included complete blood counts, blood glucose, serum electrolytes, renal function test, liver function tests, urine examination (albumin, sugar, microscopic examination, 24-h protein), ANA, chest X-ray, Barium swallow, pulmonary function test, electrocardiogram (ECG), HRCT of chest, and 4-mm punch skin biopsy from dorsum of the hand. All the patients were treated with oral methotrexate (15 mg/week) for 6 months, following standard guidelines. RESULTS: The patients included 29 (87.9%) females and four (12.1%) males with a mean age of 31.45 +/- 8.76 years. The mean duration of disease was 5.6 +/- 4.5 years (range 2 months to 15 years). All the patients had binding down of skin, 31 (93.9%) had Raynaud's phenomenon, 31 (93.9%) had pigmentary change, 21 (63.6%) had hand contractures, 17 (51.5%) had fingertip ulcers, 15 (45.5%) had dyspnoea, 14 (42.4%) had restricted mouth opening, 13 (39.4%) had telangiectasia, 11 (33.3%) had fingertip resorption, eight (24.2%) had joint complaints, six (18.2%) had dysphagia, and one (3.03%) had gangrene. On laboratory investigation ANA was positive in 29 (87.9%) patients, dsDNA was raised in only four (12.1%), baseline chest X-ray was abnormal in 18 (54.5%), HRCT was abnormal in 27 (81.8%), abnormal PFT in 32 (96.9%), abnormal ECG in five (15.2%), and barium swallow abnormality in 19 (57.5%) patients. Twenty-five patients completed the 6-month follow up. There was subjective improvement in binding down (80%), Raynaud's phenomenon (96%), fingertip ulceration (88.8%), hyperpigmentation (77.2%) and dyspnoea (45.5%). The objective parameters showed statistically significant improvement in mouth openingm, but improvement of skin score, lung function (chest radiograph, PFT, HRCT), and dysphagia was not significant at the 6-month follow up. In eight patients, treatment was continued for 1 year of methotrexate, which showed statistically significant improvement in skin score. CONCLUSION: It was concluded that methotrexate for 6 months only provides subjective improvement, and further studies after 1 year of treatment with methotrexate are recommended. PMID- 17269984 TI - Anisakis simplex and cross-reacting antigens. PMID- 17269987 TI - Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. AB - BACKGROUND: Saccharomyces boulardii is a non-pathogenic probiotic yeast considered useful against enteropathogens. AIM: To assess the effectiveness of S. boulardii in treating acute infectious diarrhoea in children. METHODS: The following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. RESULTS: Five randomized-controlled trials (619 participants) met the inclusion criteria. Combined data from four randomized-controlled trials showed that S. boulardii significantly reduced the duration of diarrhoea compared with control. The pooled weighted mean difference was -1.1 days (95% CI: -1.3 to -0.8) with a fixed model and remained significant in a random effect model. Saccharomyces boulardii significantly reduced the risk of diarrhoea on days 3, 6 and 7. Also the risk of diarrhoea lasting >7 days was significantly reduced in the S. boulardii group vs. control group (1 RCT, n = 88, RR 0.25, 95% CI: 0.08-0.83; NNT 5, 95% CI: 3-20). CONCLUSIONS: There exists a moderate clinical benefit of S. boulardii therapy in otherwise healthy infants and children with acute gastroenteritis, mainly a shorter duration of diarrhoea. However, these results should be interpreted with caution due to methodological limitations of the included studies. PMID- 17269988 TI - Is exocrine pancreatic insufficiency in adult coeliac disease a cause of persisting symptoms? AB - BACKGROUND: Patients with coeliac disease may have diarrhoea despite being on a gluten-free diet. AIM: To assess whether exocrine pancreatic insufficiency causes persisting symptoms compared with controls, we determined whether pancreatic enzyme supplementation provided symptomatic benefit in coeliac patients with chronic diarrhoea. METHODS: Patients (n = 259) were subdivided into four groups: (a) new coeliac disease (n = 57), (b) coeliac disease patients on a gluten-free diet without gastrointestinal symptoms (n = 86), (c) coeliac disease patients on a gluten-free diet with chronic diarrhoea (n = 66) and (d) patients with chronic diarrhoea without coeliac disease (n = 50). Stool frequency and weight, before and after treatment with pancreatic enzyme supplementation were recorded. RESULTS: The prevalence of a low faecal elastase-1 within the groups was: group (A) six of 57 (11%), group (B) five of 86 (6%), group (C) 20 of 66 (30%) and group (D) two of 50 (4%). Low faecal elastase-1 was more frequent in coeliac disease patients with chronic diarrhoea vs. other subgroups of coeliac disease (P < or = 0.0001) and controls (P < or = 0.0003). In 18 of 20 stool frequency reduced following pancreatic enzyme supplementation from four per day to one (P < or = 0.001). No weight increase (P = 0.3) was observed. CONCLUSIONS: Low faecal elastase is common in patients with coeliac disease and chronic diarrhoea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit. PMID- 17269989 TI - Coeliac disease and the risk of fractures - a general population-based cohort study. AB - BACKGROUND: Earlier studies have suggested that untreated coeliac disease may be associated with osteoporosis, but results are contradictory for the risk of long term fractures. AIM: To study the association between coeliac disease and fractures. METHODS: We used Cox regresson to examine the future risk of hip fracture and fracture of any type in more than 13 000 individuals with coeliac disease and 65 000 age- and sex-matched reference individuals in a general population-based cohort. RESULTS: During follow-up, 1365 first hip fractures and 4847 fractures of any type occurred. Coeliac disease was positively associated with subsequent hip fracture (hazard ratio = 2.1; 95% CI = 1.8-2.4) (in children: hazard ratio = 2.6; 95% CI = 1.1-6.2) and fractures of any type (hazard ratio = 1.4; 95% CI = 1.3-1.5) (in children: hazard ratio = 1.1; 95% CI = 1.0-1.2). The absolute excess risk of hip fractures in children with coeliac disease was 4/100 000 person-years. Incidence ratios for hip fracture in individuals with CD were around two both prior to diagnosis of coeliac disease and afterwards; this risk increase remained 20 years after diagnosis of coeliac disease. CONCLUSIONS: Individuals with coeliac disease, including children with coeliac disease, may be at increased risk of hip fracture and fracture of any type. Coeliac disease may be positively associated with long-term hip fracture risk. PMID- 17269990 TI - Gastro-oesophageal reflux disease in chronic laryngitis: prevalence and response to acid-suppressive therapy. AB - BACKGROUND: Gastro-oesophageal reflux is thought to cause chronic laryngitis through laryngopharyngeal reflux. Response of laryngitis to treatment with acid suppressive therapy supports this causal link. AIM: To determine the prevalence of gastro-oesophageal reflux disease in patients with chronic laryngitis and response to proton-pump inhibitor therapy. METHODS: Patients with chronic laryngitis were recruited. The frequency and severity of reflux and laryngeal symptoms were scored and laryngitis graded by laryngoscopy. All patients underwent esophagogastroduodenoscopy and 24-h ambulatory pH monitoring before receiving lansoprazole 30 mg b.d. for 8 weeks. RESULTS: The prevalence of gastro oesophageal reflux disease was 65.6% (21 of 32). Based on positive pH test, the prevalence was 25% (eight of 32). The change in laryngeal symptom score and laryngitis grade was significantly higher in GERD compared with non-GERD patients (P = 0.010 for both). The proportion of patients with marked/moderate improvement in laryngeal symptoms were significantly higher in patients with reflux (14 of 21, 67%) compared to those without reflux (two of 11, 18%; P = 0.026). CONCLUSIONS: The prevalence of gastro-oesophageal reflux disease amongst our patients with chronic laryngitis was high. The response to treatment with proton pump inhibitors in patients with reflux disease compared to those without underlined the critical role of acid reflux in a subset of patients with chronic laryngitis. PMID- 17269991 TI - The quantitative validation of non-endoscopic disease activity indices in ulcerative colitis. AB - BACKGROUND: Ulcerative colitis disease activity indices have not been formally validated. AIM: To analise quantitatively the psychometric and performance validity of two non-endoscopic indices for ulcerative colitis, the Simple Clinical Colitis Activity Index and the Seo Index. METHODS: In 66 patients with ulcerative colitis, the measurement of disease activity was repeated with the two non-endoscopic indices, St Mark's Index, and the Inflammatory Bowel Disease Questionnaire. Psychometric validity was evaluated by measuring the content, construct, criterion-convergent and criterion-predictive validity on a 0-1 scale. Performance validity was evaluated by measuring the reproducibility and responsiveness on a 0-1 scale. RESULTS: The Simple Clinical Colitis Activity Index had good to excellent psychometric and performance validity, while the Seo Index had moderate to excellent psychometric validity and moderate to good performance validity. The Simple Clinical Colitis Activity Index had weaknesses in content validity and in responsiveness. The Seo Index had weaknesses in content validity, construct validity and responsiveness. CONCLUSIONS: These two non-endoscopic indices for ulcerative colitis have good psychometric and performance validity, and are now the most rigorously validated disease activity indices for ulcerative colitis. The Simple Clinical Colitis Activity Index appears to have better overall validity. Quantitative evaluation identifies weaknesses in disease activity indices, and can lead to better disease activity indices for ulcerative colitis. PMID- 17269992 TI - Systematic review: oral bowel preparation for colonoscopy. AB - BACKGROUND: There are many published trials of colon cleansing regimens for colonoscopy but no clear consensus regarding relative performance. AIM: To identify high quality controlled trials comparing two or more bowel preparation regimens and to compare efficacy and tolerability. METHODS: A comprehensive systematic review was carried out to identify candidate studies. Quality appraisal was carried out on all identified studies. Results were meta-analysed where possible and qualitatively compared if not. RESULTS: Eighty-two studies qualified for analysis. Polyethylene glycol and sodium phosphate were the most frequently investigated preparations. There was no significant efficacy difference between the two, but sodium phosphate was better tolerated. Sodium picosulphate/magnesium citrate, a commonly prescribed preparation, was investigated in four studies, with no clear benefit over other regimens demonstrated. Safety was not recognized as a problem in the randomized controlled trials. Published case series demonstrate that sodium phosphate is associated with the highest risk of clinically significant electrolyte disturbances. CONCLUSION: Shortcomings in study design limit the value of many of the studies. Based on these results, no single bowel preparation emerges as consistently superior. New preparations are required that combine better efficacy and tolerability, in addition to rigorous new validated study designs, allowing unequivocal comparisons to be made. PMID- 17269993 TI - Meta-analysis: the efficacy of proton pump inhibitors for laryngeal symptoms attributed to gastro-oesophageal reflux disease. AB - BACKGROUND: Many investigators have proposed an association between gastro oesophageal reflux disease and laryngo-pharyngeal symptoms, suggesting that medical or surgical therapy for reflux may be useful. AIM: To perform a meta analysis assessing the effectiveness of medical or surgical therapy for reflux disease in adult patients with laryngeal or pharyngeal symptoms presumed to be due to gastro-oesophageal reflux disease. METHODS: Randomized controlled trials comparing medical or surgical treatments for gastro-oesophageal reflux disease against placebo were identified by searching MEDLINE (1966-September 2005), EMBASE (1974-September 2005), the CCRCT (until September 2005) and abstracts from gastroenterology and ENT meetings. The relative risks of reporting symptomatic improvement or resolution of symptoms was evaluated using a random-effects model. RESULTS: Five studies using high-dose proton pump inhibitor as intervention met the inclusion criteria and were included in the meta-analysis. No surgical studies met inclusion criteria. The pooled relative risk was 1.18 (95% confidence interval: 0.81-1.74). There was no heterogeneity between studies but evidence of significant publication bias. Sub-group analysis performed evaluating Jadad scores and symptom type, did not change the relative risk. CONCLUSIONS: Therapy with a high-dose proton pump inhibitor is no more effective than placebo in producing symptomatic improvement or resolution of laryngo-pharyngeal symptoms. Further studies are necessary to identify the characteristics of patients that may respond to proton pump inhibitor therapy. PMID- 17269994 TI - Meta-analysis: ondansetron for vomiting in acute gastroenteritis in children. AB - BACKGROUND: Vomiting is a common sympton in children with gastroenteritis, but its treatment remains controversial. AIM: To investigate potential beneficial effects of ondansetron, compared with placebo or no intervention, in treating vomiting during acute gastroenteritis in children. METHODS: The following electronic databases were searched through August 2006: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials (RCTs) were included. RESULTS: Four RCTs involving 490 patients with vomiting during acute gastroenteritis were included. Combined data from three RCTs (n = 466) showed that ondansetron compared with the control significantly increased the chance for vomiting cessation soon after drug administration [relative risk (RR): 1.3, 95% confidence interval (CI): 1.2-1.5, number needed to treat (NNT): 5, 95% CI: 4-8], but this effect was not observed at 24 h (three RCTs, n = 144, RR 1.2, 95% CI: 0.9-1.7). Ondansetron significantly reduced the risk of intravenous rehydration (two RCTs, n = 359, RR 0.4, 95% CI: 0.3-0.7, NNT 7, 95% CI: 5-14). Outcome measures not significantly different after ondansetron treatment were the need for hospitalization and return emergency department visits. CONCLUSIONS: Despite some clinical benefits, there is insufficient evidence to recommend the routine use of ondansetron for vomiting during acute gastroenteritis in children. PMID- 17269995 TI - GI Epidemiology: nutritional epidemiology. AB - BACKGROUND: Nutritional epidemiology is the assessment of diet and its relationship to disease aetiology in populations. The choice of dietary assessment method depends on the disease pathology. Events such as cancer that are chronic and complicated by exposure time require methods that capture consumption patterns of populations over a period of years. Although several methods of dietary assessment exist for collecting information on groups of individuals, their application to epidemiologic studies requires an understanding of the effect of variability in nutrient intake, sources of measurement error, and statistical issues unique to the study of nutritional epidemiology. AIM: This review provides an overview of commonly-used methods of dietary assessments in epidemiologic studies, and identifies their strengths and limitations and application to epidemiologic study designs. It concludes with a brief discussion of assumptions of nutrient databases and objectives of energy-adjustment and measurement error correction models. CONCLUSIONS: Nutritional epidemiology has contributed significantly to our understanding of the relationships between diet and disease. Ongoing investigations that further characterize important exposure periods (early life, in utero) and clarify associations within the context of genetic susceptibility will continue to elucidate our understanding of the pathophysiology of complex diseases, and support future recommendations for disease prevention. PMID- 17269996 TI - Efficacy and safety of short-term adalimumab treatment in patients with active Crohn's disease who lost response or showed intolerance to infliximab: a prospective, open-label, multicentre trial. AB - BACKGROUND: The use of tumour necrosis factor antagonists has changed the therapeutic approach to Crohn's disease. AIM: To determine response and remission rates associated with the 4-week induction phase of adalimumab treatment in patients with luminal and/or fistulizing Crohn's disease, who have lost response to or become intolerant of infliximab. METHODS: In this multicentre, prospective, open-label, observational, 52-week study, 50 adults received an induction dose of adalimumab (160 mg at baseline followed by 80 mg at week 2). RESULTS: Of the 36 patients with luminal Crohn's disease, 83% achieved clinical response [> or =70 point reduction in the Crohn's Disease Activity Index (CDAI) score] and 42% achieved clinical remission (CDAI score <150) at week 4. Of the 22 patients with fistulizing disease, five (23%) experienced fistula remission (complete closure of all fistulas that were draining at baseline), and nine (41%) experienced fistula improvement (> or =50% decrease in the number of fistulas that were draining at baseline) at week 4. Of the 19 adverse events, most [13 (68%)] were mild, and no serious or infectious adverse events occurred. CONCLUSIONS: Adalimumab may be an effective alternative in patients with luminal and/or fistulizing Crohn's disease who have lost response to or become intolerant of infliximab. PMID- 17269997 TI - Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term results. AB - BACKGROUND: Anti-tumour necrosis factor-alpha antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor-alpha suppressive properties. AIM: To investigate the long-term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease. METHODS: Twenty-eight patients with refractory moderate-severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5-2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission. RESULTS: Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28). CONCLUSIONS: Thalidomide seems to be effective in inducing long-term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose-dependent, thus allowing long-term remission before drug suspension. PMID- 17269998 TI - Combined type-1 plasminogen activator inhibitor and NOD2/CARD15 genotyping predicts complicated Crohn's disease behaviour. AB - BACKGROUND: NOD2/CARD15 gene variants have not been universally associated with stricturing behaviour in Crohn's disease. Other behaviour modifying genes could explain these results. AIM: To study the combined influence of NOD2/CARD15 variants and 4G/4G genotype of type-1 plasminogen activator inhibitor (PAI-1) gene on Crohn's disease behaviour. METHODS: One hundred and seventy Crohn's disease patients were studied prospectively, with a mean follow-up of 7+/- 6 years. Disease behaviour was registered by using two criteria: the Vienna classification and a non-hierarchical classification based on the behavioural Vienna categories. RESULTS: In the multivariate analysis for stricturing behaviour according to the Vienna categories, only absence of colonic disease (OR, 4.0; 95% CI: 1.49-11.1; P = 0.006) was an independent predictive factor. However, in the multivariate analysis for stricturing disease applying a non hierarchical criteria, ileal disease (OR, 4.19; 95% CI: 1.30-13.5; P = 0.01), and carrying both NOD2/CARD15 variants and the 4G/4G PAI-1 genotype (OR, 5.02; 95% CI: 1.44-17.48; P = 0.01) were independent predictive factors. In the multivariate analysis for penetrating behaviour, the 4G/4G PAI-1 (OR, 3.10; 95% CI: 1.54-6.23; P = 0.001) and male sex (OR, 2.44; 95% CI: 1.30-4.60; P = 0.005) were independent predictive factors irrespective of criteria applied. CONCLUSIONS: Combined PAI-1 and NOD2/CARD15 genotyping predict complicated Crohn's disease. Patients with these variants could benefit from early interventions. PMID- 17269999 TI - Determining the proximal extent of ulcerative colitis: white cell scan correlates well with histological assessment. AB - BACKGROUND: Assessing the extent of ulcerative colitis determines therapeutic strategies and provides prognostic information. Colonoscopy with mucosal biopsy is considered unsafe in patients with severe disease. AIM: To assess the correlation between proximal extent of ulcerative colitis as determined by Technitium-99-m hexamethylpropylene amine oxime labelled leucocyte scan (white cell scan) with that determined by histological assessment. METHODS: One hundred and thirty-five patients, with histologically-confirmed ulcerative colitis, who had a white cell scan and histological assessment of colonic inflammation within 6 months of each other, during the years 1991-2004, were included. Overall agreement, quadratic-weighted kappa (kappa) and polychoric correlations (rho) were calculated to estimate the inter-rater reliability. RESULTS: The correlation between white cell scan and histological extent was excellent (kappa = 0.7 rho = 0.8). Macroscopic appearance on colonoscopy did not correlate as well with histological extent (kappa = 0.62 and rho = 0.67). White cell scans correlated significantly better in patients with extensive disease (P = 0.02). Colonoscopy predicted disease extent more accurately in patients with limited colitis (P = 0.002). CONCLUSIONS: Proximal extent of ulcerative colitis determined by white cell scans correlates well with histological assessment especially in patients with more extensive disease. White cell scans offer a reasonable alternative to colonoscopy with mucosal biopsies in determining the proximal extent of colitis. PMID- 17270000 TI - The changing incidence of oesophageal and gastric adenocarcinoma by anatomic sub site. AB - BACKGROUND: The incidence rates of gastric and oesophageal adenocarcinoma are changing significantly, but little is known about specific sub-sites. AIM: To use a population-based approach to describe the trends in the site-specific incidence of oesophageal and gastric adenocarcinoma. METHODS: Using the Rochester Epidemiology Project, all cases of gastric and oesophageal adenocarcinoma among Olmsted County, Minnesota, residents first diagnosed between 1971 and 2000 were identified (n = 186). Complete in-patient and out-patient records were reviewed and site determined from pathological, surgical, endoscopic and radiological reports. RESULTS: Between the decades of 1971-1980 and 1991-2000, the incidence of oesophageal adenocarcinoma increased significantly from 0.4 to 2.5 per 100 000 person-years. The incidence of adenocarcinoma of the oesophagogastric junction also increased from a rate of 0.6 to 2.2 per 100 000 person-years. The incidence rate of cancer involving the gastric cardia was stable but the incidence of adenocarcinoma involving distal gastric sites declined. Combined oesophageal and oesophagogastric junction adenocarcinoma (4.7 per 1 000 000 person-years) was as common as gastric adenocarcinoma (3.4 per 100 000 person-years) in 1991-2000. CONCLUSIONS: The incidence rates of adenocarcinoma involving proximal gastric sub sites do not appear to be increasing in a manner similar to those involving oesophageal sub-sites. PMID- 17270001 TI - Chronic celecoxib users more often show regression of gastric intestinal metaplasia after Helicobacter pylori eradication. AB - BACKGROUND AND AIM: To test whether the chronic users of celecoxib, a selective cyclo-oxygenase-2 inhibitor, had less Helicobacter pylori-related intestinal metaplasia or if such users' intestinal metaplasia could be prone to disappear after H. pylori eradication. METHODS: The study enrolled 150 chronic celecoxib users and 216 non-users who underwent pan-endoscopy to detect H. pylori infection and its related intestinal metaplasia. One hundred and three H. pylori-infected patients with intestinal metaplasia (43 chronic celecoxib users and 60 non-users) received anti-H. pylori therapy and completed the 12-month follow-up to survey the regression of intestinal metaplasia by mean intestinal metaplasia score. RESULTS: There were no differences in the prevalence of H. pylori-related intestinal metaplasia between the chronic celecoxib users and controls (P > 0.05). On the 12th month of follow-up, chronic celecoxib users had a lower mean intestinal metaplasia score (1.2 vs. 1.8, P < 0.005) and a higher regression rate of intestinal metaplasia (42% vs. 20%, P = 0.027) than non-users. CONCLUSIONS: With H. pylori infection, chronic celecoxib users still showed limited effects to decrease intestinal metaplasia. Nevertheless, celecoxib should be promising to assist H. pylori eradication for the control of gastric intestinal metaplasia and cancer risk. PMID- 17270002 TI - Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single centre. AB - BACKGROUND: Tegaserod has been shown to be effective in chronic constipation in Western population. Aim We investigated if tegaserod is equally effective in Chinese population. MATERIALS AND METHODS: Two hundred and fifty patients were randomized to a double-blinded 8-week treatment of tegaserod 6 mg b.d. or placebo. Response during weeks 1-4 was defined as an increase in complete spontaneous bowel motion >/=1/week. Secondary efficacy included response during weeks 1-8, individual symptoms and scores, quality of life and global assessment of bowel habits and constipation. RESULTS: One hundred and nine patients from the treatment group and 107 from the placebo group completed the 8-week treatment. Responder rates was 47.7% vs. 29% for the treatment and placebo groups (P = 0.005). The sustained complete spontaneous bowel motion rate was 29.4% vs. 15.7% in the two groups (P = 0.016). The response rates were higher than that reported previously in the Caucasian studies. There was improvement in the scores for stool form scale, bothersomeness of constipation, abdominal distension/bloating and satisfaction of bowel habit (P < 0.05). The mental score was higher in the treatment group (46.8 +/- 9 vs. 43.6 +/- 10, P = 0.01). CONCLUSIONS: Tegaserod is effective in relieving chronic constipation in Chinese population. The efficacy observed may be higher than that in Western population. PMID- 17270003 TI - An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis. AB - BACKGROUND: Fatigue is a debilitating symptom which frequently impairs the quality of life of patients with primary biliary cirrhosis (PBC). Although the mechanisms underpinning fatigue in PBC remain unclear, there is an emerging consensus that CNS mechanisms play a key role. It has recently been shown that there is a strong association between abnormalities in sleep regulation, in particular excessive daytime somnolence, and fatigue severity in PBC. The CNS acting drug modafinil has an established role in the treatment of excessive daytime somnolence in non-liver disease states. AIM: To explore, in an open label study, the responses of PBC patients suffering from significant daytime somnolence and associated fatigue to modafinil therapy. METHODS: All patients in the series (n = 21) underwent daytime somnolence assessment using the Epworth Sleepiness Scale and PBC symptom assessment using the PBC-40, a multi-domain, disease specific, psychometrically robust quality of life measure. Modafinil was started at a dose of 100 mg/day and was titrated according to tolerability and response. Patients underwent repeat Epworth Sleepiness Scale and PBC-40 assessment after 2 months of treatment. RESULTS: Significant improvement was seen in Epworth Sleepiness Scale scores with modafinil therapy [15 +/- 3 vs. 8 +/- 6, P < 0.0005 (intention-to-treat analysis)]. An equally significant improvement in fatigue severity was also seen [PBC-40 fatigue domain score (46 +/- 6 vs. 34 +/- 12, P < 0.0001) (intention-to-treat analysis)]. CONCLUSIONS: Open label modafinil therapy was associated, where tolerated by patients, with improvement in excessive daytime somnolence and associated fatigue in PBC. Further study in placebo-controlled trials is warranted. PMID- 17270004 TI - The Short-Form Leeds Dyspepsia Questionnaire validation study. AB - BACKGROUND: Assessment of symptoms should be the primary outcome measure in dyspepsia clinical trials. This requires a reliable, valid and responsive questionnaire that measures the frequency and severity of dyspepsia. The Leeds Dyspepsia Questionnaire fulfils these characteristics, but is long and was not designed for self-completion, so a shorter questionnaire was developed (the Short Form Leeds Dyspepsia Questionnaire). AIM: To assess the acceptability, interpretability, internal consistency, reliability, validity and responsiveness of the Short-Form Leeds Dyspepsia Questionnaire in primary and secondary care. METHODS: Unselected primary and secondary care patients completed the Short-Form Leeds Dyspepsia Questionnaire. Test-retest reliability was assessed after 2 days. Validity was measured by comparison with general practitioners' diagnosis. Sensitivity analysis and logistic regression were employed to determine the most valid scoring system. Responsiveness was determined before and after treatment for endoscopically proven disease. RESULTS: The Short-Form Leeds Dyspepsia Questionnaire was administered to 388 primary care and 204 secondary care patients. The Pearson coefficient for test-retest reliability was 0.93. The Short Form Leeds Dyspepsia Questionnaire had a sensitivity of 77% and a specificity of 75%. A highly significant response to change was observed (P < 0.005). CONCLUSIONS: The Short-Form Leeds Dyspepsia Questionnaire is a reliable, valid and responsive self-completed outcome measure for quantifying the frequency and severity of dyspepsia symptoms, which is shorter and more convenient than the Leeds Dyspepsia Questionnaire. PMID- 17270005 TI - Consequences of frequent nocturnal gastro-oesophageal reflux disease among employed adults: symptom severity, quality of life and work productivity. AB - BACKGROUND: Effects of frequent nocturnal symptoms of gastro-oesophageal reflux disease (GERD-FNS) on health-related quality of life (HRQOL) and work productivity are not well documented. AIM: To assess symptom severity, production loss, and HRQOL among employed adults with and without GERD-FNS. METHODS: Using several validated outcome measures in a web survey design, GERD was pre-specified as GERD Symptom and Medication Questionnaire score >9, and > or =1 episode of heartburn or acid regurgitation during the preceding week. GERD-FNS patients were those reporting > or =2 symptom-nights during the previous week; their outcomes were compared with those of patients having minimal or no nocturnal symptoms (GERD-NNS) and vs. non-GERD controls. RESULTS: Data were collected from 1002 GERD patients (476 GERD-FNS, 526 GERD-NNS) and 513 controls. Severe symptoms were more common, sleep abnormalities were more frequent (P < 0.0001) and SF-36 scores lower (P < 0.05, all scores) among GERD-FNS patients vs. GERD-NNS patients. GERD related work loss was greater among those with GERD-FNS vs. GERD-NNS (P < 0.0001). Work loss and functional limitations were more pronounced when comparing GERD-FNS cases vs. non-GERD controls. CONCLUSION: Employed adults with frequent nocturnal GERD report more severe symptoms, and are associated with impaired sleep, HRQOL and work productivity compared with controls and patients with minimal or no nocturnal symptoms. PMID- 17270006 TI - Combined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24-h intragastric pH in healthy volunteers. AB - AIM: To compare antisecretory effects of rabeprazole and esomeprazole after single and repeat dosing in Helicobacter pylori-negative healthy volunteers. METHODS: Results were pooled from three smaller, open, crossover, randomized studies to obtain data from 80 subjects. The studies compared: (a) 5 days' dosing of 20 mg rabeprazole and esomeprazole (n = 24); (b) single doses of rabeprazole 20 mg and esomeprazole 40 mg (n = 27) and (c) 5 days' dosing of rabeprazole 10 mg and esomeprazole 20 mg (n = 29). Washout periods were > or =14 days. Intragastric pH was recorded continuously for 24 h on days 0, 1 and 5. RESULTS: Single doses of rabeprazole 20 mg maintained 24-h intragastric pH >4 for longer than esomeprazole 20 mg (45% vs. 32%; P < 0.001); rabeprazole 20 mg and esomeprazole 40 mg were equivalent in their effects. After 5 days' dosing, rabeprazole 20 mg maintained pH >4 for longer than esomeprazole 20 mg (62% vs. 56%; P = 0.046); the reverse was true for esomeprazole 20 mg vs. rabeprazole 10 mg (56% vs. 48%; P = 0.035). In general, intragastric pH AUC during 0-5 h after dosing was higher after esomeprazole than rabeprazole, whereas the reverse was true during the night. CONCLUSIONS: The order of effects on 24-h pH was: rabeprazole 10 mg < or = esomeprazole 20 mg < rabeprazole 20 mg = esomeprazole 40 mg. Esomeprazole acts faster, whereas rabeprazole's effect lasts longer. PMID- 17270007 TI - Pharmacodynamic effects of single doses of rabeprazole 20 mg and pantoprazole 40 mg in patients with GERD and nocturnal heartburn. AB - BACKGROUND: Rabeprazole and pantoprazole are both used for symptomatic treatment of gastro-oesophageal reflux disease (GERD). Speed and duration of acid suppression and intensity of effect after a single dose may be important pharmacodynamic properties in clinical use. AIM: To compare antisecretory effects of single doses of rabeprazole and pantoprazole in patients with GERD and a history of nocturnal heartburn. METHODS: An open-label, randomized, two-way crossover, clinical pharmacology study was conducted. Twenty-nine Helicobacter pylori-negative GERD patients (17 men, mean age 44 years), with a history of nocturnal heartburn (mean frequency 4.7 episodes/week), received a single dose of rabeprazole 20 mg or pantoprazole 40 mg, with a 14-day 'washout'. Intragastric pH was recorded continuously from 24 h before to 24 h after dosing. RESULTS: Mean area under the intragastric pH-time curve (AUC) was significantly higher after dosing with rabeprazole 20 mg than with pantoprazole 40 mg in all time intervals analysed, including night (P 3 and >4 was significantly greater after rabeprazole than pantoprazole in all time intervals (P 2 cm) (P = 0.027 and P = 0.031, respectively). Based on univariate analysis, patients with aberrant methylation of the Cyclin D2 promoter had a significantly worse chance of disease-free survival than those without methylation (P = 0.021). Our results suggest that aberrant promoter methylation of the Cyclin D2 gene is significantly associated with patient prognosis in epithelial ovarian cancer. PMID- 17270029 TI - Specific expression of hepatocyte nuclear factor-1beta in the ovarian clear cell adenocarcinoma and its application to cytological diagnosis. AB - Ascitic cytological diagnosis is critical, but ovarian adenocarcinoma cells and reactive mesothelial cells can be difficult to distinguish because they usually have atypical cell nuclei and increased nuclear/cytoplasmic ratios. Previous studies using DNA microarrays have demonstrated that hepatocyte nuclear factor 1beta (HNF-1beta) is expressed specifically in clear cell adenocarcinoma (CCC). Thus, in the present study, we investigated the usefulness of HNF-1beta as an immunocytochemical diagnostic marker of CCC in ascitic specimens. We first confirmed that HNF-1beta expression levels were significantly higher in CCC than in non-CCC (i.e. serous adenocarcinoma, mucinous adenocarcinoma and endometrioid adenocarcinoma) in 55 surgical specimens at both the mRNA (P < 0.05) and protein (P < 0.05) levels by real-time polymerase chain reaction and immunohistochemistry, respectively. Immunocytochemistry of 60 cytological specimens showed significant positivity in CCC cases whereas all non-CCC cells, except for three endometrioid adenocaricnoma cases, and mesothelial cells in the background stained negatively for anti-HNF-1beta antibody (P < 0.05). The sensitivity and specificity were calculated to be 0.955 and 0.921, respectively. Immmunostaining patterns of HNF-1beta on cytological specimens were similar to those observed on histopathological ovarian specimens from the same patients. Double immunohistochemical staining using anti-HNF-1beta antibody and HBME-1, a mesothelium-specific monoclonal antibody, confirmed that anti-HNF-1beta antibody distinguished CCC cells and mesothelial cells. In conclusion, our findings indicate the specific expression of HNF-1beta in ovarian CCC and possible clinical applications of HNF-1beta immunocytochemical staining for the differential cytopathological diagnosis of CCC from non-CCC, as well as from mesothelial cells using cytological specimens from ovarian carcinoma patients. PMID- 17270030 TI - Coffee consumption and the risk of endometrial cancer: Evidence from a case control study of female hormone-related cancers in Japan. AB - Coffee has become a popular beverage worldwide. Caffeine, a major ingredient of coffee, has been proposed to have a favorable affect on the modulation of circulating estrogen levels and therefore may be of importance in developments on hormone-related cancers. However, epidemiological evidence is limited and inconsistent. We examined the relationship between intake of coffee and hormone related cancer risk among Japanese women using data from the hospital-based epidemiological research program at Aichi Cancer Center (HERPACC). In total, 2122 breast, 229 endometrial and 166 ovarian cancer cases were included, and 12 425 women, confirmed as free of cancer, were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. A statistically significant inverse association between risk of endometrial cancer and coffee consumption was noted in Japanese women, with no clear association evident for breast and ovarian cancer risk. Compared to non-drinker, the OR of daily drinking of 1-2 cups and 3 or more cups per day for endometrial cancer were 0.64 (95% CI: 0.43-0.94) and 0.41 (95% CI: 0.19-0.87), respectively, and the linear trend was also statistically significant (P < 0.01). However, there was no statistically significant association between caffeine intake and endometrial cancer. In summary, the results of the present study suggest that coffee consumption reduces the risk of endometrial cancer in Japanese subjects. Given the scarcity of studies of coffee intake and endometrial cancer and other hormone-dependent cancer risk, additional investigations are warranted. PMID- 17270031 TI - Depletion of CD4+CD25+ regulatory T cells enhances interleukin-2-induced antitumor immunity in a mouse model of colon adenocarcinoma. AB - Interleukin 2 (IL)-2 induces antitumor immunity and clinical responses in melanoma and renal cell carcinoma. However, IL-2 also increases the number of CD4(+)CD25(+) regulatory T (Treg) cells that suppress antitumor immune responses. The aim of the present study was to elucidate the effect of depletion of Treg cells on IL-2-induced antitumor immunity. IL-2-transfected mouse colon adenocarcinoma (MC38/IL-2) cells were implanted subcutaneously or intrahepatically into male C57BL/6 mice, and tumor growth and the proportion of tumor-infiltrating lymphocytes with Treg-cell depletion in response to treatment with anti-CD25 monoclonal antibody (PC61) were determined. In mice treated with phosphate-buffered saline, 40-60% of MC38/IL-2 tumors were rejected. In contrast, all MC38/IL-2 tumors were rejected in mice treated with PC61. The number of tumor infiltrating CD8(+) T cells in mice treated with PC61 was approximately twice that in mice treated with PBS. The numbers of tumor-infiltrating CD4(+) and natural killer cells were also increased significantly. To test the antimetastatic effects of IL-2 treatment in combination with Treg-cell depletion, human recombinant IL-2 (rIL-2) and PC61 were administered to mice implanted with MC38/mock cells in the spleen, and hepatic metastasis was investigated. The average liver weight in mice treated with rIL-2 plus PC61 was 1.04 +/- 0.03 g, less than that in mice treated with rIL-2 (2.04 +/- 0.51 g) or PC61 alone (1.81 +/- 0.38 g). We conclude that IL-2-induced antitumor immunity is enhanced by Treg cell depletion and is due to expansion of the tumor-infiltrating cytotoxic CD8(+) T-cell population. PMID- 17270032 TI - 4-S-Cysteaminylphenol-loaded magnetite cationic liposomes for combination therapy of hyperthermia with chemotherapy against malignant melanoma. AB - Tyrosine analogs are good candidates for developing melanoma chemotherapies because melanogenesis is inherently toxic and expressed uniquely in melanocytic cells. The sulfur homolog of tyrosine, 4-S-cysteaminylphenol (4-S-CAP), was shown to be a substrate of melanoma tyrosinase and can cause selective cytotoxicity of melanocytes and melanoma cells. Previously, in order to improve the adsorption of magnetite nanoparticles to target cell surfaces, and generate heat in an alternating magnetic field (AMF) for cancer hyperthermia, we produced hyperthermia using magnetite cationic liposomes (MCL) that have a positive charge at the liposomal surface. In the present study, we constructed 4-S-CAP-loaded MCL (4-S-CAP/MCL), which act as a novel modality, combining melanoma-specific chemotherapy by 4-S-CAP with intracellular hyperthermia mediated by MCL. The 4-S CAP/MCL exerted 4-S-CAP-mediated anticancer effects on B16 melanoma cells in vitro and in vivo. Moreover, after intratumoral injection of 4-S-CAP/MCL in vivo, the melanoma nodules were heated to 45 degrees C under an AMF. Significantly higher therapeutic effects were observed in mice treated with the combination therapy mediated by 4-S-CAP/MCL plus AMF irradiation compared with mice treated with 4-S-CAP/MCL alone (without AMF) or mice treated with hyperthermia alone (MCL + AMF irradiation). These results suggest that this novel therapeutic tool is applicable to the treatment of malignant melanoma. PMID- 17270033 TI - Synergistic growth inhibition by acyclic retinoid and vitamin K2 in human hepatocellular carcinoma cells. AB - Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. However, effective chemopreventive and chemotherapeutic agents for this cancer have not yet been developed. In clinical trials acyclic retinoid (ACR) and vitamin K(2) (VK(2)) decreased the recurrence rate of HCC. In the present study we examined the possible combined effects of ACR or another retinoid 9-cis retinoic acid (9cRA) plus VK(2) in the HuH7 human HCC cell line. We found that the combination of 1.0 microM ACR or 1.0 microM 9cRA plus 10 microM VK(2) synergistically inhibited the growth of HuH7 cells without affecting the growth of Hc normal human hepatocytes. The combined treatment with ACR plus VK(2) also acted synergistically to induce apoptosis in HuH7 cells. Treatment with VK(2) alone inhibited phosphorylation of the retinoid X receptor (RXR)alpha protein, which is regarded as a critical factor for liver carcinogenesis, through inhibition of Ras activation and extracellular signal-regulated kinase phosphorylation. Moreover, the inhibition of RXRalpha phosphorylation by VK(2) was enhanced when the cells were cotreated with ACR. The combination of retinoids plus VK(2) markedly increased both the retinoic acid receptor responsive element and retinoid X receptor responsive element promoter activities in HuH7 cells. Our results suggest that retinoids (especially ACR) and VK(2) cooperatively inhibit activation of the Ras/MAPK signaling pathway, subsequently inhibiting the phosphorylation of RXRalpha and the growth of HCC cells. This combination might therefore be effective for the chemoprevention and chemotherapy of HCC. PMID- 17270034 TI - Genomic profiling of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32. AB - Genome-wide array-based comparative genomic hybridization analysis of malignant pleural mesotheliomas (MPM) was carried out to identify regions that display DNA copy number alterations. Seventeen primary tumors and nine cell lines derived from 22 individuals were studied, some of them originating from the same patients. Regions of genomic aberrations observed in >20% of individuals were 1q, 5p, 7p, 8q24 and 20p with gains, and 1p36.33, 1p36.1, 1p21.3, 3p21.3, 4q22, 4q34 qter, 6q25, 9p21.3, 10p, 13q33.2, 14q32.13, 18q and 22q with losses. Two regions at 1p32.1 and 11q22 showed a high copy gain. The 1p32.1 region contained a protooncogene, JUN, and we further demonstrated overexpression of JUN with real time polymerase chain reaction analysis. As MPM cell lines did not overexpress JUN, our findings suggested that induction of JUN expression was involved in the development of MPM cells in vivo, which also might result in gene amplification in a subset of MPM. Meanwhile, the most frequent alteration was the 9p21.3 deletion, which includes the p16(INK4a)/p14(ARF) locus. With polymerase chain reaction analysis, we determined the extent of the homozygous deletion regions of the p16(INK4a)/p14(ARF) locus in MPM cell lines, which indicated that the deletion regions varied among cell lines. Our results with array comparative genomic hybridization analysis provide new insights into the genetic background of MPM, and also give some clues to develop a new molecular target therapy for MPM. PMID- 17270038 TI - GEVALT: an integrated software tool for genotype analysis. AB - BACKGROUND: Genotype information generated by individual and international efforts carries the promise of revolutionizing disease studies and the association of phenotypes with alleles and haplotypes. Given the enormous amounts of public genotype data, tools for analyzing, interpreting and visualizing these data sets are of critical importance to researchers. In past works we have developed algorithms for genotypes phasing and tag SNP selection, which were shown to be quick and accurate. Both algorithms were available until now only as batch executables. RESULTS: Here we present GEVALT (GEnotype Visualization and ALgorithmic Tool), a software package designed to simplify and expedite the process of genotype analysis, by providing a common interface to several tasks relating to such analysis. GEVALT combines the strong visual abilities of Haploview with our quick and powerful algorithms for genotypes phasing (GERBIL), tag SNP selection (STAMPA) and permutation testing for evaluating significance of association. All of the above are provided in a visually appealing and interactive interface. CONCLUSION: GEVALT is an integrated viewer that uses state of the art phasing and tag SNP selection algorithms. By streamlining the application of GERBIL and STAMPA together with strong visualization for assessment of the results, GEVALT makes the algorithms accessible to the broad community of researchers in genetics. PMID- 17270037 TI - Classification of microarray data using gene networks. AB - BACKGROUND: Microarrays have become extremely useful for analysing genetic phenomena, but establishing a relation between microarray analysis results (typically a list of genes) and their biological significance is often difficult. Currently, the standard approach is to map a posteriori the results onto gene networks in order to elucidate the functions perturbed at the level of pathways. However, integrating a priori knowledge of the gene networks could help in the statistical analysis of gene expression data and in their biological interpretation. RESULTS: We propose a method to integrate a priori the knowledge of a gene network in the analysis of gene expression data. The approach is based on the spectral decomposition of gene expression profiles with respect to the eigenfunctions of the graph, resulting in an attenuation of the high-frequency components of the expression profiles with respect to the topology of the graph. We show how to derive unsupervised and supervised classification algorithms of expression profiles, resulting in classifiers with biological relevance. We illustrate the method with the analysis of a set of expression profiles from irradiated and non-irradiated yeast strains. CONCLUSION: Including a priori knowledge of a gene network for the analysis of gene expression data leads to good classification performance and improved interpretability of the results. PMID- 17270039 TI - High prevalence of respiratory symptoms among workers in the development section of a manually operated coal mine in a developing country: a cross sectional study. AB - BACKGROUND: Few studies of miners have been carried out in African countries; most are from South Africa, where the working conditions are assumed to be better than in the rest of Africa. Several studies have focused on respiratory disorders among miners, but development workers responsible for creating underground road ways have not been studied explicitly. This is the first study assessing the associations between exposure to dust and quartz and respiratory symptoms among coal mine workers in a manually operated coal mine in Tanzania, focusing on development workers, as they have the highest exposure to coal dust. METHODS: A cross-sectional study was carried out among 250 production workers from a coal mine. Interviews were performed using modified standardized questionnaires to elicit information on occupational history, demographics, smoking habits and acute and chronic respiratory symptoms. The relationships between current dust exposure as well as cumulative respirable dust and quartz and symptoms were studied by group comparisons as well as logistic regression. RESULTS: Workers from the development group had the highest dust exposure, with arithmetic mean of 10.3 mg/m3 for current respirable dust and 1.268 mg/m3 for quartz. Analogous exposure results for mine workers were 0.66 mg/m3 and 0.03 mg/m3, respectively; and for other development workers were 0.88 mg/m3 and 0.10 mg/m3, respectively. The workers from the development section had significantly higher prevalence of the acute symptoms of dry cough (45.7%), breathlessness (34.8%) and blocked nose (23.9%). In addition, development workers had significantly more chronic symptoms of breathlessness (17.0%) than the mine workers (6.4%) and the other production workers (2.4%). The highest decile of cumulative exposure to respirable dust was significantly associated with cough (OR = 2.91, 95% CI 1.06, 7.97) as were cumulative exposure to quartz and cough (OR = 2.87, CI 1.05, 7.88), compared with the reference consisting of the group of workers with the lowest quartile of the respective cumulative exposure. CONCLUSION: The development workers in a coal mine had more acute and chronic respiratory symptoms than the mine and the other production workers. In addition, there was an association between high cumulative coal dust and respiratory symptoms. PMID- 17270040 TI - Day care cataract surgery in Central and Southern Italy: a multicentric survey. AB - BACKGROUND: Cataract day surgery has rapidly gained worldwide acceptance, because the new surgical techniques and costs are generally lower than those involved in ordinary hospitalization. Cataract surgery serves as a proxy indicator of the trend towards day surgery hospitalization in Italy and, therefore, of regional variability in health-care delivery and cost. The aim of this study was to update the diffusion of cataract day surgery through various surgical ophthalmological centers in central and southern Italy during 2005. METHODS: A two-stage stratified cluster sampling method was used to draw a sample of Cataract Surgery Unit from Ophthalmic Units of central and southern Italy. A questionnaire was sent to 25 cataract surgery centers in nine health districts that represented the range of establishments (public, private, accredited or otherwise) in which cataract surgery is performed. Data were collected on numbers of procedures performed in 2005, hospital admission type, time from the onset of cataract day surgery, surgical procedure, and presence of other surgical centers. RESULTS: The response rate was 42% (10 surveys), resulting in at least one completed questionnaire for each of these 9 districts. There is a positive trend towards day surgery hospitalization in all surgical centers. The percentage of patients treated as outpatients during 2005 varied from 50-60% (Avellino, Naples, Campobasso), to 80-90% (Rome, Bari), up to 90-100% (Catania, Palermo, Siracusa and Trapani), with an increasing trend in all the centers studied. Few differences were found in surgical procedures, and these were statistically insignificant. CONCLUSION: Our results confirm a positive trend towards day surgery in place of hospital inpatient admission for cataract surgery. This trend is expected to close the existing regional gap in Italy. Increased efficiency is an overriding need for the National Health Service in order to improve the rationalization of resources. PMID- 17270041 TI - An informatic pipeline for the data capture and submission of quantitative proteomic data using iTRAQ. AB - BACKGROUND: Proteomics continues to play a critical role in post-genomic science as continued advances in mass spectrometry and analytical chemistry support the separation and identification of increasing numbers of peptides and proteins from their characteristic mass spectra. In order to facilitate the sharing of this data, various standard formats have been, and continue to be, developed. Still not fully mature however, these are not yet able to cope with the increasing number of quantitative proteomic technologies that are being developed. RESULTS: We propose an extension to the PRIDE and mzData XML schema to accommodate the concept of multiple samples per experiment, and in addition, capture the intensities of the iTRAQ reporter ions in the entry. A simple Java-client has been developed to capture and convert the raw data from common spectral file formats, which also uses a third-party open source tool for the generation of iTRAQ reported intensities from Mascot output, into a valid PRIDE XML entry. CONCLUSION: We describe an extension to the PRIDE and mzData schemas to enable the capture of quantitative data. Currently this is limited to iTRAQ data but is readily extensible for other quantitative proteomic technologies. Furthermore, a software tool has been developed which enables conversion from various mass spectrum file formats and corresponding Mascot peptide identifications to PRIDE formatted XML. The tool represents a simple approach to preparing quantitative and qualitative data for submission to repositories such as PRIDE, which is necessary to facilitate data deposition and sharing in public domain database. The software is freely available from http://www.mcisb.org/software/PrideWizard. PMID- 17270042 TI - Health sector reforms and human resources for health in Uganda and Bangladesh: mechanisms of effect. AB - BACKGROUND: Despite the expanding literature on how reforms may affect health workers and which reactions they may provoke, little research has been conducted on the mechanisms of effect through which health sector reforms either promote or discourage health worker performance. This paper seeks to trace these mechanisms and examines the contextual framework of reform objectives in Uganda and Bangladesh, and health workers' responses to the changes in their working environments by taking a 'realistic evaluation' approach. METHODS: The study findings were generated by triangulating both qualitative and quantitative methods of data collection and analysis among policy technocrats, health managers and groups of health providers. Quantitative surveys were conducted with over 700 individual health workers in both Bangladesh and Uganda and supplemented with qualitative data obtained from focus group discussions and key interviews with professional cadres, health managers and key institutions involved in the design, implementation and evaluation of the reforms of interest. RESULTS: The reforms in both countries affected the workforce through various mechanisms. In Bangladesh, the effects of the unification efforts resulted in a power struggle and general mistrust between the two former workforce tracts, family planning and health. However positive effects of the reforms were felt regarding the changes in payment schemes. Ugandan findings show how the workforce responded to a strong and rapidly implemented system of decentralisation where the power of new local authorities was influenced by resource constraints and nepotism in recruitment. On the other hand, closer ties to local authorities provided the opportunity to gain insight into the operational constraints originating from higher levels that health staff were dealing with. CONCLUSION: Findings from the study suggest that a) reform planners should use the proposed dynamic responses model to help design reform objectives that encourage positive responses among health workers b) the role of context has been underestimated and it is necessary to address broader systemic problems before initiating reform processes, c) reform programs need to incorporate active implementation research systems to learn the contextual dynamics and responses as well as have inbuilt program capacity for corrective measures d) health workers are key stakeholders in any reform process and should participate at all stages and e) some effects of reforms on the health workforce operate indirectly through levels of satisfaction voiced by communities utilising the services. PMID- 17270043 TI - New pandemics: HIV and AIDS, HCV and chronic hepatitis, influenza virus and flu. AB - New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Quebec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting. PMID- 17270044 TI - Knowledge, perceived stigma, and care-seeking experiences for sexually transmitted infections: a qualitative study from the perspective of public clinic attendees in Rio de Janeiro, Brazil. AB - BACKGROUND: An estimated 12 million sexually transmitted infections (STIs) are documented in Brazil per year. Given the scope of this public health challenge and the importance of prompt treatment and follow-up counseling to reduce future STI/HIV-related risk behavior, we sought to qualitatively explore STI clinic experiences among individuals diagnosed with STIs via public clinics in Rio de Janeiro, Brazil. The study focused on eliciting the perspective of clinic users with regard to those factors influencing their STI care-seeking decisions and the health education and counseling which they received during their clinic visit. METHODS: Thirty semi-structured interviews were conducted with heterosexual men and women and men who have sex with men presenting with STIs at two public clinics. Content analysis was conducted by coding transcripts of audio-taped interviews for key domains of interest and comparing and synthesizing code output across participants and sub-groups. Thematic narratives were then developed per each of the study sub-groups. RESULTS: Salient themes that emerged from participant narratives included the importance of low STI-related knowledge and high perceived stigma, both STI-related and other types of social stigma, on STI care-seeking delays. However, there are indications in the data that the level of STI-related knowledge and the amount and types of stigma experienced vary across the study sub-groups suggesting the need for further research on the significance and program relevance of these potential differences. Interview findings also suggest that such barriers to care seeking are not adequately addressed through ongoing health education and counseling efforts at public STI clinics and in turn critical opportunities for STI/HIV prevention are currently being missed. CONCLUSION: Information, communication and education regarding early recognition and prompt care-seeking for STIs should be developed, with consideration given to the possibility of tailoring messages tailored to specific sub-groups. To promote prompt treatment-seeking, interventions must also address both STI-specific and other forms of social stigma which may limit access to care. Efforts to further assess and respond to barriers related to the delivery of quality health education and counseling within the context of public STI clinics are also needed. PMID- 17270045 TI - Boolean networks using the chi-square test for inferring large-scale gene regulatory networks. AB - BACKGROUND: Boolean network (BN) modeling is a commonly used method for constructing gene regulatory networks from time series microarray data. However, its major drawback is that its computation time is very high or often impractical to construct large-scale gene networks. We propose a variable selection method that are not only reduces BN computation times significantly but also obtains optimal network constructions by using chi-square statistics for testing the independence in contingency tables. RESULTS: Both the computation time and accuracy of the network structures estimated by the proposed method are compared with those of the original BN methods on simulated and real yeast cell cycle microarray gene expression data sets. Our results reveal that the proposed chi square testing (CST)-based BN method significantly improves the computation time, while its ability to identify all the true network mechanisms was effectively the same as that of full-search BN methods. The proposed BN algorithm is approximately 70.8 and 7.6 times faster than the original BN algorithm when the error sizes of the Best-Fit Extension problem are 0 and 1, respectively. Further, the false positive error rate of the proposed CST-based BN algorithm tends to be less than that of the original BN. CONCLUSION: The CST-based BN method dramatically improves the computation time of the original BN algorithm. Therefore, it can efficiently infer large-scale gene regulatory network mechanisms. PMID- 17270046 TI - Cone rod dystrophies. AB - Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, and the visual prognosis is poor. Management aims at slowing down the degenerative process, treating the complications and helping patients to cope with the social and psychological impact of blindness. PMID- 17270047 TI - Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene. AB - BACKGROUND: Respiratory syncytial virus (RSV) causes severe bronchiolitis and is a risk factor for asthma. Since there is no commercially available vaccine against RSV, a short interfering RNA against the RSV-NS1gene (siNS1) was developed and its potential for decreasing RSV infection and infection-associated inflammation in rats was tested. METHODS: Plasmids encoding siNS1 or an unrelated siRNA were complexed with a chitosan nanoparticle delivery agent and administered intranasally. Control animals received a plasmid for a non-specific siRNA. After expression of the plasmid in lung cells for 24 hours, the rats were intranasally infected with RSV. RESULTS: Prophylaxis with siNS1 significantly reduced lung RSV titers and airway hyperreactivity to methacholine challenge compared to the control group. Lung sections from siNS1-treated rats showed a sizable reduction in goblet cell hyperplasia and in lung infiltration by inflammatory cells, both characteristics of asthma. Also, bronchoalveolar lavage samples from siNS1 treated animals had fewer eosinophils. Treatment of rats with siNS1 prior to RSV exposure was effective in reducing virus titers in the lung and in preventing the inflammation and airway hyperresponsiveness associated with the infection that has been linked to development of asthma. CONCLUSION: The use of siNS1 prophylaxis may be an effective method for preventing RSV bronchiolitis and potentially reducing the later development of asthma associated with severe respiratory infections. PMID- 17270048 TI - A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. AB - BACKGROUND: Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment. RESULTS: This screen identified no more than three transcripts; XIST, and two unique noncoding nuclear enriched abundant transcripts (NEAT) RNAs strikingly located less than 70 kb apart on human chromosome 11: NEAT1, a noncoding RNA from the locus encoding for TncRNA, and NEAT2 (also known as MALAT-1). While the two NEAT transcripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding RNAs. NEAT2 is extraordinarily well conserved for a noncoding RNA, more so than even XIST. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA FISH analyses suggest that these noncoding RNAs function in mRNA metabolism as they demonstrate an intimate association of these RNA species with SC35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts, NEAT1 localizes to the periphery of such domains, whereas the neighboring transcript, NEAT2, is part of the long-sought polyadenylated component of nuclear speckles. CONCLUSION: Our genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2. The function of these noncoding RNAs in mRNA metabolism is suggested by their high levels of conservation and their intimate association with SC35 splicing domains in multiple mammalian species. PMID- 17270049 TI - A community study of the effect of particulate matter on blood measures of inflammation and thrombosis in an elderly population. AB - BACKGROUND: The mechanism behind the triggering effect of fine particulate matter (PM) air pollution on cardiovascular events remains elusive. We postulated that elevated levels of PM would be associated with increased blood levels of inflammatory and thrombotic markers in elderly individuals. We also hypothesized that elevated PM would increase levels of cytokines in individuals with heart disease. METHODS: We measured these blood markers in 47 elderly individuals with (23) and without (16 COPD and 8 healthy) cardiovascular disease (CVD) on 2 or 3 mornings over a 5 or 10-day period between February 2000 and March 2002. Blood measures were paired with residence level outdoor PM measured by nephelometry. Analyses determined the within-individual effect of 24-hour averaged outdoor PM on blood measures. RESULTS: Analyses found no statistically significant effect of a same day 10 ug/m3 increase in fine PM on log transformed levels of CRP 1.21 fold-rise [95% CI: 0.86, 1.70], fibrinogen 1.02 fold-rise [95% CI: 0.98, 1.06], or D-dimer 1.02 fold-rise [95% CI: 0.88, 1.17] in individuals with CVD. One-day lagged analyses in the CVD subgroup found similar null results. These same models found no change in these blood markers at the same-day or 1-day lag in the group without CVD. In 21 individuals with CVD, a 10 mug/m3 increase in same-day PM was associated with a 1.3 fold-rise [95% CI: 1.1, 1.7] in the level of monocyte chemoattractant protein-1. CONCLUSION: We did not find consistent effects of low ambient levels of PM on blood measures of inflammation or thrombosis in elderly individuals. PMID- 17270050 TI - Liver transplant and hepatitis C in methadone maintenance therapy: a case report. AB - Methadone maintenance therapy for the treatment of opioid dependence continues to carry a social stigma. Until recently, patients on methadone were not considered for liver transplantation. We describe the first case of a patient on methadone who received a liver transplant for end stage liver disease and was successfully treated for recurrent hepatitis C. More than five years post transplant and three years post viral clearance, the patient continues to do well and is stable on low dose methadone. This case emphasizes the need to reconsider the non-evidence based policy adopted by transplant centers that require methadone maintenance therapy patients to stop methadone prior to consideration for transplant evaluation. PMID- 17270051 TI - Closing the access gap for health innovations: an open licensing proposal for universities. AB - BACKGROUND: This article centers around a proposal outlining how research universities could leverage their intellectual property to help close the access gap for health innovations in poor countries. A recent deal between Emory University, Gilead Sciences, and Royalty Pharma is used as an example to illustrate how 'equitable access licensing' could be put into practice. DISCUSSION: While the crisis of access to medicines in poor countries has multiple determinants, intellectual property protection leading to high prices is well-established as one critical element of the access gap. Given the current international political climate, systemic, government-driven reform of intellectual property protection seems unlikely in the near term. Therefore, we propose that public sector institutions, universities chief among them, adopt a modest intervention--an Equitable Access License (EAL)--that works within existing trade-law and drug-development paradigms in order to proactively circumvent both national and international obstacles to generic medicine production. Our proposal has three key features: (1) it is prospective in scope, (2) it facilitates unfettered generic competition in poor countries, and (3) it centers around universities and their role in the biomedical research enterprise. Two characteristics make universities ideal agents of the type of open licensing proposal described. First, universities, because they are upstream in the development pipeline, are likely to hold rights to the key components of a wide variety of end products. Second, universities acting collectively have a strong negotiating position with respect to other players in the biomedical research arena. Finally, counterarguments are anticipated and addressed and conclusions are drawn based on how application of the Equitable Access License would have changed the effects of the licensing deal between Emory and Gilead. PMID- 17270052 TI - Heritable clustering and pathway discovery in breast cancer integrating epigenetic and phenotypic data. AB - BACKGROUND: In order to recapitulate tumor progression pathways using epigenetic data, we developed novel clustering and pathway reconstruction algorithms, collectively referred to as heritable clustering. This approach generates a progression model of altered DNA methylation from tumor tissues diagnosed at different developmental stages. The samples act as surrogates for natural progression in breast cancer and allow the algorithm to uncover distinct epigenotypes that describe the molecular events underlying this process. Furthermore, our likelihood-based clustering algorithm has great flexibility, allowing for incomplete epigenotype or clinical phenotype data and also permitting dependencies among variables. RESULTS: Using this heritable clustering approach, we analyzed methylation data obtained from 86 primary breast cancers to recapitulate pathways of breast tumor progression. Detailed annotation and interpretation are provided to the optimal pathway recapitulated. The result confirms the previous observation that aggressive tumors tend to exhibit higher levels of promoter hypermethylation. CONCLUSION: Our results indicate that the proposed heritable clustering algorithms are a useful tool for stratifying both methylation and clinical variables of breast cancer. The application to the breast tumor data illustrates that this approach can select meaningful progression models which may aid the interpretation of pathways having biological and clinical significance. Furthermore, the framework allows for other types of biological data, such as microarray gene expression or array CGH data, to be integrated. PMID- 17270053 TI - Alcohol imagery on New Zealand television. AB - BACKGROUND: To examine the extent and nature of alcohol imagery on New Zealand (NZ) television, a content analysis of 98 hours of prime-time television programs and advertising was carried out over 7 consecutive days' viewing in June/July 2004. The main outcome measures were number of scenes in programs, trailers and advertisements depicting alcohol imagery; the extent of critical versus neutral and promotional imagery; and the mean number of scenes with alcohol per hour, and characteristics of scenes in which alcohol featured. RESULTS: There were 648 separate depictions of alcohol imagery across the week, with an average of one scene every nine minutes. Scenes depicting uncritical imagery outnumbered scenes showing possible adverse health consequences of drinking by 12 to 1. CONCLUSION: The evidence points to a large amount of alcohol imagery incidental to storylines in programming on NZ television. Alcohol is also used in many advertisements to market non-alcohol goods and services. More attention needs to be paid to the extent of alcohol imagery on television from the industry, the government and public health practitioners. Health education with young people could raise critical awareness of the way alcohol imagery is presented on television. PMID- 17270054 TI - Intron Evolution and Information processing in the DNA polymerase alpha gene in spirotrichous ciliates: a hypothesis for interconversion between DNA and RNA deletion. AB - BACKGROUND: The somatic DNA molecules of spirotrichous ciliates are present as linear chromosomes containing mostly single-gene coding sequences with short 5' and 3' flanking regions. Only a few conserved motifs have been found in the flanking DNA. Motifs that may play roles in promoting and/or regulating transcription have not been consistently detected. Moreover, comparing subtelomeric regions of 1,356 end-sequenced somatic chromosomes failed to identify more putatively conserved motifs. RESULTS: We sequenced and compared DNA and RNA versions of the DNA polymerase alpha (pol alpha) gene from nine diverged spirotrichous ciliates. We identified a G-C rich motif aaTACCGC(G/C/T) upstream from transcription start sites in all nine pol alpha orthologs. Furthermore, we consistently found likely polyadenylation signals, similar to the eukaryotic consensus AAUAAA, within 35 nt upstream of the polyadenylation sites. Numbers of introns differed among orthologs, suggesting independent gain or loss of some introns during the evolution of this gene. Finally, we discuss the occurrence of short direct repeats flanking some introns in the DNA pol alpha genes. These introns flanked by direct repeats resemble a class of DNA sequences called internal eliminated sequences (IES) that are deleted from ciliate chromosomes during development. CONCLUSION: Our results suggest that conserved motifs are present at both 5' and 3' untranscribed regions of the DNA pol alpha genes in nine spirotrichous ciliates. We also show that several independent gains and losses of introns in the DNA pol alpha genes have occurred in the spirotrichous ciliate lineage. Finally, our statistical results suggest that proven introns might also function in an IES removal pathway. This could strengthen a recent hypothesis that introns evolve into IESs, explaining the scarcity of introns in spirotrichs. Alternatively, the analysis suggests that ciliates might occasionally use intron splicing to correct, at the RNA level, failures in IES excision during developmental DNA elimination. PMID- 17270055 TI - Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence and absence of food. AB - BACKGROUND: The objective of this study was to compare the pharmacokinetic profile of a novel, once-daily, controlled-release formulation of hydromorphone (OROS hydromorphone) under fasting conditions with that immediately after a high fat breakfast in healthy volunteers. The effect of the opioid antagonist naltrexone on fasting hydromorphone pharmacokinetics also was evaluated. METHODS: In an open-label, three-way, crossover study, 30 healthy volunteers were randomized to receive a single dose of 16 mg OROS hydromorphone under fasting conditions, 16 mg OROS hydromorphone under fed conditions, or 16 mg OROS hydromorphone under fasting conditions with a naltrexone 50-mg block. Plasma samples taken pre-dose and at regular intervals up to 48 hours post-dose were assayed for hydromorphone concentrations. Analysis of variance was performed on log-transformed data; for mean ratios of 0.8 to 1.2 (20%), differences were considered minimal. Bioequivalence was reached if 90% confidence intervals (CI) of treatment mean ratios were between 80% and 125%. RESULTS: The mean geometric ratios of the fed and fasting treatment groups for maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-t; AUC0-infinity) were within 20%. Confidence intervals were within 80% to 125% for AUC0-t and AUC0 infinity but were slightly higher for Cmax (105.9% and 133.3%, respectively). With naltrexone block, the hydromorphone Cmax increased by 39% and the terminal half-life decreased by 4.5 hours. There was no significant change in Tmax, AUC0-t or AUC0-infinity. CONCLUSION: Standard bioavailability measures show minimal effect of food on the bioavailability of hydromorphone from OROS hydromorphone. Naltrexone co-administration results in a slight increase in the rate of absorption but not the extent of absorption. PMID- 17270056 TI - KSHV/HHV-8 and HIV infection in Kaposi's sarcoma development. AB - Kaposi's sarcoma (KS) is a highly and abnormally vascularized tumor-like lesion affecting the skin, lymphnodes and viscera, which develops from early inflammatory stages of patch/plaque to late, nodular tumors composed predominant of spindle cells (SC). These SC are infected with the Kaposi's sarcoma-associated herpesvirus or human herpesvirus-8 (KSHV/HHV-8). KS is promoted during HIV infection by various angiogenic and pro-inflammatory factors including HIV-Tat. The latency associated nuclear antigen type 1 (LANA-1) protein is well expressed in SC, highly immunogenic and considered important in the generation and maintenance of HHV-8 associated malignancies. Various studies favour an endothelial origin of the KS SC, expressing "mixed" lymphatic and vascular endothelial cell markers, possibly representing hybrid phenotypes of endothelial cells (EC). A significant number of SC during KS development are apparently not HHV8 infected, which heterogeneity in viral permissiveness may indicate that non infected SC may continuously be recruited in to the lesion from progenitor cells and locally triggered to develop permissiveness to HHV8 infection. In the present study various aspects of KS pathogenesis are discussed, focusing on the histopathological as well as cytogenetic and molecular genetic changes in KS. PMID- 17270057 TI - A common origin of complex life cycles in parasitic flatworms: evidence from the complete mitochondrial genome of Microcotyle sebastis (Monogenea: Platyhelminthes). AB - BACKGROUND: The parasitic Platyhelminthes (Neodermata) contains three parasitic groups of flatworms, each having a unique morphology, and life style: Monogenea (primarily ectoparasitic), Trematoda (endoparasitic flukes), and Cestoda (endoparasitic tapeworms). The evolutionary origin of complex life cyles (multiple obligate hosts, as found in Trematoda and Cestoda) and of endo-/ecto parasitism in these groups is still under debate and these questions can be resolved, only if the phylogenetic position of the Monogenea within the Neodermata clade is correctly estimated. RESULTS: To test the interrelationships of the major parasitic flatworm groups, we estimated the phylogeny of the Neodermata using complete available mitochondrial genome sequences and a newly characterized sequence of a polyopisthocotylean monogenean Microcotyle sebastis. Comparisons of inferred amino acid sequences and gene arrangement patterns with other published flatworm mtDNAs indicate Monogenea are sister group to a clade of Trematoda+Cestoda. CONCLUSION: Results confirm that vertebrates were the first host for stem group neodermatans and that the addition of a second, invertebrate, host was a single event occurring in the Trematoda+Cestoda lineage. In other words, the move from direct life cycles with one host to complex life cycles with multiple hosts was a single evolutionary event. In association with the evolution of life cycle patterns, our result supports the hypothesis that the most recent common ancestor of the Neodermata giving rise to the Monogenea adopted vertebrate ectoparasitism as its initial life cycle pattern and that the intermediate hosts of the Trematoda (molluscs) and Cestoda (crustaceans) were subsequently added into the endoparasitic life cycles of the Trematoda+Cestoda clade after the common ancestor of these branched off from the monogenean lineage. Complex life cycles, involving one or more intermediate hosts, arose through the addition of intermediate hosts and not the addition of a vertebrate definitive host. Additional evidence is required from monopisthocotylean monogeneans in order to confirm the monophyly of the group. PMID- 17270058 TI - Pharmacokinetic investigation of dose proportionality with a 24-hour controlled release formulation of hydromorphone. AB - BACKGROUND: The purpose of this study was investigate the dose proportionality of a novel, once-daily, controlled-release formulation of hydromorphone that utilizes the OROS Push-Pull osmotic pump technology. METHODS: In an open-label, four-way, crossover study, 32 healthy volunteers were randomized to receive a single dose of OROS hydromorphone 8, 16, 32, and 64 mg, with a 7-day washout period between treatments. Opioid antagonism was provided by three or four doses of naltrexone 50 mg, given at 12-hour intervals pre- and post-OROS hydromorphone dosing. Plasma samples for pharmacokinetic analysis were collected pre-dose and at regular intervals up to 48 hours post-dose (72 hours for the 64-mg dose), and were assayed for hydromorphone concentration to determine peak plasma concentration (Cmax), time at which peak plasma concentration was observed (Tmax), terminal half-life (t1/2), and area under the concentration-time curve for zero to time t (AUC0-t) and zero to infinity (AUC0-infinity). An analysis of variance (ANOVA) model on untransformed and dose-normalized data for AUC0-t, AUC0 infinity, and Cmax was used to establish dose linearity and proportionality. RESULTS: The study was completed by 31 of 32 subjects. Median Tmax (12.0-16.0 hours) and mean t1/2 (10.6-11.0 hours) were found to be independent of dose. Regression analyses of Cmax, AUC0-48, and AUC0-infinity by dose indicated that the relationship was linear (slope, P < or = 0.05) and that the intercept did not differ significantly from zero (P > 0.05). Similar analyses with dose-normalized parameters also indicated that the slope did not differ significantly from zero (P > 0.05). CONCLUSION: The pharmacokinetics of OROS hydromorphone are linear and dose proportional for the 8, 16, 32, and 64 mg doses. PMID- 17270059 TI - Substitution treatment for opioid addicts in Germany. AB - BACKGROUND: After a long and controversial debate methadone maintenance treatment (MMT) was first introduced in Germany in 1987. The number of patients in MMT- first low because of strict admission criteria--increased considerably since the 1990s up to some 65,000 at the end of 2006. In Germany each general practitioner (GP), who has completed an additional training in addiction medicine, is allowed to prescribe substitution drugs to opioid dependent patients. Currently 2,700 GPs prescribe substitution drugs. Psychosocial care should be made available to all MMT patients. RESULTS: The results of research studies and practical experiences clearly indicate that patients benefit substantially from MMT with improvements in physical and psychological health. MMT proves successful in attaining high retention rates (65% to 85% in the first years, up to 50% after more than seven years) and plays a major role in accessing and maintaining ongoing medical treatment for HIV and hepatitis. MMT is also seen as a vital factor in the process of social re-integration and it contributes to the reduction of drug related harms such as mortality and morbidity and to the prevention of infectious diseases. Some 10% of MMT patients become drug-free in the long run. Methadone is the most commonly prescribed substitution medication in Germany, although buprenorphine is attaining rising importance. Access to MMT in rural areas is very patchy and still constitutes a problem. There are only few employment opportunities for patients participating in MMT, although regular employment is considered unanimously as a positive factor of treatment success. Substitution treatment in German prisons is heterogeneous in access and treatment modalities. Access is very patchy and the number of inmates in treatment is limited. Nevertheless, substitution treatment plays a substantial part in the health care system provided to drug users in Germany. CONCLUSION: In Germany, a history of substitution treatment spanning 20 years has meanwhile accumulated a wealth of experience, e.g. in the development of research on health care services, guidelines and the implementation of quality assurance measures. Implementing substitution treatment with concomitant effects and treatment elements such as drug history-taking, dosage setting, co-use of other psychoactive substances (alcohol, benzodiazepines, cocaine), management of 'difficult patient populations', and integration into the social environment has been arranged successfully. Also psychosocial counseling programmes adjuvant to substitution treatment have been established and, in the framework of a pilot project on heroin-based treatment, standardised manuals were developed. Research on allocating opioid users to the 'right' form of therapy at the 'right' point in time is still a challenge, though the pilot project 'heroin-based treatment' brought experience with patients who do not benefit from methadone treatment. There is also expertise in the treatment of specific co-morbidity such as HIV/AIDS, hepatitis and psychiatric disorders. The promotion and involvement of self-help groups plays an important part in the process of successful substitution treatment. PMID- 17270060 TI - Classification tree analysis of second neoplasms in survivors of childhood cancer. AB - BACKGROUND: Reports on childhood cancer survivors estimated cumulative probability of developing secondary neoplasms vary from 3.3% to 25% at 25 years from diagnosis, and the risk of developing another cancer to several times greater than in the general population. METHODS: In our retrospective study, we have used the classification tree multivariate method on a group of 849 first cancer survivors, to identify childhood cancer patients with the greatest risk for development of secondary neoplasms. RESULTS: In observed group of patients, 34 develop secondary neoplasm after treatment of primary cancer. Analysis of parameters present at the treatment of first cancer, exposed two groups of patients at the special risk for secondary neoplasm. First are female patients treated for Hodgkin's disease at the age between 10 and 15 years, whose treatment included radiotherapy. Second group at special risk were male patients with acute lymphoblastic leukemia who were treated at the age between 4.6 and 6.6 years of age. CONCLUSION: The risk groups identified in our study are similar to the results of studies that used more conventional approaches. Usefulness of our approach in study of occurrence of second neoplasms should be confirmed in larger sample study, but user friendly presentation of results makes it attractive for further studies. PMID- 17270061 TI - Effects of acute and chronic cooling on cardiorespiratory depression in rodents. AB - The cardiovascular and ventilatory responses of the Wistar rat (a non-hibernator) and the Syrian hamster (a hibernator) to acute and chronic cold exposure were investigated. The acute lowering of core temperature (T(c) = 22 degrees C, hypothermia) compared with normothermia (T(c) = 37 degrees C) and hyperthermia (T(c) = 40 degrees C) was used to examine the underlying differences in the extent of cold adaptation. In euthermic rats, acutely induced hypothermia resulted in a pronounced reduction in heart rate (f(H) reduced by 55%; P < 0.01), a modest but significant elevation of mean arterial blood pressure (mABP increased by 16%; P < 0.05), and a marked reduction in respiratory frequency (f(R) reduced by 64%; P < 0.01). All parameters returned to baseline values on returning T(c) to 37 degrees C, with a modest overshoot on acute hyperthermia. These data are consistent with the depressive effect of low temperature on biological rate functions and increased vagal tone in the cold, while matching f(R) to a lowered metabolic rate (MO(2)). Cold acclimation had little effect on this pattern of response, suggesting that any adaptive increase in thermogenesis is limited. Euthermic hamsters also showed a significant reduction in f(H) on acute cooling (74%; P < 0.01). In contrast to rats, hamsters developed a significant decrease in mABP (52%; P < 0.01) and maintained a relatively high f(R) (4%; n.s.). These data suggest a resetting of the baroreflex and relative hyperventilation, consistent with an elevated MO(2) associated with enhanced nonshivering thermogenesis. Cold acclimation had little effect on thermal sensitivity, though the response curves were displaced to produce a relative hypertension and tachycardia at a given T(c). These data suggest a reduced cardiorespiratory coupling in the hibernator compared with the non-hibernator. PMID- 17270062 TI - Managing and analysing a large health-care system database for predicting in hospital mortality among acute myocardial infarction patients. AB - There is increasing interest in the identification of predictors of risk for in hospital mortality due to acute myocardial infarction (AMI). This study identified significant predictors of in-hospital mortality among AMI patients using a patient level clinical database. The study population consisted of 4167 cases admitted between October 1999 and April 2001 with a principal diagnosis of AMI to 36 hospitals in three US states. Of the 182 available variables in the clinical data set, 30 variables were used as candidate predictors, and 19 showed significant univariate association with AMI in-hospital mortality. By applying multiple logistic regression and stepwise selection, a final prediction model for AMI in-hospital mortality was developed. Variables included in the final model were age, arrived from cardiac rehabilitation centre, cardiopulmonary resuscitation (CPR) on arrival, Killip class, AMI with co-morbid conditions, AMI with complications, percutaneous transluminal coronary angioplasty (PTCA) performed, beta-blockers given, angiotensin-converting enzyme (ACE) inhibitors given, Plavix given. A 10-variable in-hospital mortality prediction model for AMI patients, which includes both risk factors and beneficial treatment procedures, was developed. chi(2) goodness of fit test suggested a good fit for the model. PMID- 17270063 TI - A case study into labour turnover within an NHS Trust. AB - This paper investigates turnover in a British NHS Trust, to find out why staff left and whether factors identified in the literature with regards to improving turnover were pertinent to the organization. The research also investigated staff groups with high turnover--staff with less than 12 months service, and the unqualified nursing staff group--to ascertain whether there were any reasons for leaving or areas of dissatisfaction particular to these groups. The outcomes of the research complied with much of the published research with some interesting differences. The main reasons for leaving were identified as moving house, promotion or career development and taking up education and training opportunities elsewhere. There was no evidence of 'level of pay', commonly given as a significant influence behind turnover, as a reason for leaving. It was also found that the retention strategies identified in the published research were mainly applicable to the research, with evidence to support the improvement of line management skills, training and development, career development, appraisal, communications and induction in order to reduce turnover. There was less evidence for introducing work-life balance policies, improving communications, pay and working relationships as retention strategies. Recommendations for future management of labour turnover within the NHS Trust and elsewhere are made, with observations about the validity of some existing models. The core contribution of this research is in adding to the body of knowledge about labour turnover issues. This is of value to those working in the UK health-care and wider public sector. Specific recommendations for future research are made. PMID- 17270064 TI - Improving the recruitment and return of nurses and allied health professionals: a quantitative study. AB - The United Kingdom National Health Service (NHS) is continuing to experience recruitment and retention problems of nursing and allied health profession staff. Consequently, the need to study and understand the key factors that encourage or dissuade people to work for the NHS remains a major research and policy issue. This study provides well-focused, independent research to explore how the NHS can be made more attractive for potential new recruits and possible returners. The views of potential recruits and returners interested in working for the NHS as either a qualified nurse, physiotherapist or radiographer were explored through a postal questionnaire survey which achieved a response rate of 23%. Analysis of the results indicate that the strongest predictor of intention to work for the NHS in one of the three professions was the attitude held by respondents. These attitudes in turn were most influenced by the extent to which people perceived that NHS work as a qualified nurse, physiotherapist or radiographer offered positive features, i.e. rewarding career, teamwork and a chance to help people and to get to know them. The views of family and friends regarding working for the NHS were also important as was the belief in one's ability to secure an NHS job. PMID- 17270065 TI - Reforming emergency care: Primary Care Trust power in action research. AB - OBJECTIVES: A Primary Care Trust (PCT) used its position as lead commissioner in a health economy to search for efficiency gains and to improve the patient journey through accident and emergency (A&E) services in a hard-pressed acute hospital. The project generated an action research approach. As a by-product, we developed a model of the hospital system based on a case study that can be replicated and used to set utilization targets at the micro-level of the hospital organization. This addresses a gap in the literature on hospital utilization that currently focuses on macro-population levels of analysis or simulation models that demand complex data. Primary and secondary care services, in contrast, require a pragmatic model of utilization supported by a few key, readily available data items. METHODS: Mixed quantitative and qualitative methods were adopted in an approach of collaborative enquiry among stakeholders of the health economy. We used the flexible planning tenet of action research that evolved into the subjective meaning tenet by which, to achieve authoritative findings, it was necessary to broaden the line of enquiry to address participants' perceptions. RESULTS: We have described the current patient flow and a redesigned pathway through A&E services together with targets and action required to reduce admissions, delayed discharges and diagnostic waits in the emergency hospital system. Primary care had a key role in changing the culture, communication and treatment within A&E services. CONCLUSION: (i) This study was rapid and sustained a high level of energy and purpose among stakeholders. Action research is an appropriate method to apply to transformational change in the modernization of health-care systems; (ii) Modelling of system dynamics is a critical dimension to the success of whole system change; (iii) Primary care commissioning power is an under-used, but influential, lever for change. At a point when the PCT commissioning structure is under threat, this project exemplifies primary care's ability to engineer change in acute hospital services. PMID- 17270066 TI - Modular organization and hospital performance. AB - The concept of modularization represents a modern form of organization, which contains the vertical disaggregation of the firm and the use of market mechanisms within hierarchies. The objective of this paper is to examine whether the use of modular structures has a positive effect on hospital performance. The empirical section makes use of multiple regression analyses and leads to the main result that modularization does not have a positive effect on hospital performance. However, the analysis also finds out positive efficiency effects of two central ideas of modularization, namely process orientation and internal market mechanisms. PMID- 17270067 TI - Rurality, remoteness and the change process: evidence from a study of maternity services in the north of Scotland. AB - There is a wealth of material on 'how to do' change plus empirical work revealing change process complexity. In health care, the relevance of context is highlighted, but studies of rural health-care change have focused on community impacts. There is little to inform health-care managers of how remoteness and rurality impact upon change processes. This study considered Scottish maternity units and aimed to identify issues in the change process associated with rurality and remoteness. Six units were purposively selected and 131 interviews were conducted with managers, staff and community members over 15 months. Analysis induced themes pertinent to remoteness and rurality. These included: perceived 'distance' between senior managers imposing change and the wider community of staff and residents; perceptions of community vulnerability; and tensions arising from working in small teams and living in small communities. The study provides useful insights for rural managers at a time of considerable service reconfiguration. PMID- 17270069 TI - Near infrared spectroscopy in the development of solid dosage forms. AB - The use of near infrared (NIR) spectroscopy has rapidly grown partly due to demands of process analytical applications in the pharmaceutical industry. Furthermore, newest regulatory guidelines have advanced the increase of the use of NIR technologies. The non-destructive and non-invasive nature of measurements makes NIR a powerful tool in characterization of pharmaceutical solids. These benefits among others often make NIR advantageous over traditional analytical methods. However, in addition to NIR, a wide variety of other tools are naturally also available for analysis in pharmaceutical development and manufacturing, and those can often be more suitable for a given application. The versatility and rapidness of NIR will ensure its contribution to increased process understanding, better process control and improved quality of drug products. This review concentrates on the use of NIR spectroscopy from a process research perspective and highlights recent applications in the field. PMID- 17270070 TI - Determination of amorphous content in the pharmaceutical process environment. AB - The amorphous state has different chemical and physical properties compared with a crystalline one. Amorphous regions in an otherwise crystalline material can affect the bioavailability and the processability. On the other hand, crystalline material can function as nuclei and decrease the stability of an amorphous system. The aim of this study was to determine amorphous content in a pharmaceutical process environment using near infrared (NIR) and Raman spectroscopic techniques together with multivariate modelling tools. Milling was used as a model system for process-induced amorphization of a crystalline starting material, alpha-lactose monohydrate. In addition, the crystallization of amorphous material was studied by storing amorphous material, either amorphous lactose or trehalose, at high relative humidity conditions. The results show that both of the spectroscopic techniques combined with multivariate methods could be applied for quantitation. Preprocessing, as well as the sampling area, was found to affect the performance of the models. Standard normal variate (SNV) transformation was the best preprocessing approach and increasing the sampling area was found to improve the models. The root mean square error of prediction (RMSEP) for quantitation of amorphous lactose using NIR spectroscopy was 2.7%, when a measuring setup with a larger sampling area was used. When the sampling area was smaller, the RMSEPs for lactose and trehalose were 4.3% and 4.2%, respectively. For Raman spectroscopy, the RMSEPs were 2.3% and 2.5% for lactose and trehalose, respectively. However, for the optimal performance of a multivariate model, all the physical forms present, as well as the process environment itself, have to be taken into consideration. PMID- 17270071 TI - Process analytical applications of Raman spectroscopy. AB - There is an increasing demand for new approaches to understand the chemical and physical phenomena that occur during pharmaceutical unit operations. Obtaining real-time information from processes opens new perspectives for safer and more efficient manufacture of pharmaceuticals. Raman spectroscopy provides a molecular level insight into processing, and therefore it is a future process analytical tool. In this review, different applications of Raman spectroscopy in the field of process analysis of pharmaceutical solid dosage forms are summarized. In addition, pitfalls associated with interfacing to the process environment and challenges within data management are discussed. PMID- 17270072 TI - Raman spectroscopy for quantitative analysis of pharmaceutical solids. AB - Raman spectroscopy is experiencing a surge in interest in solid-state pharmaceutical applications. It is rapid, non-destructive, no sample preparation is required and measurements can be made in aqueous environments. It can be used for not only qualitative, but also quantitative, analysis. In this paper, the use of Raman spectroscopy for quantitative analysis of pharmaceutical solids is reviewed. The technique has been used for chemical and physical form analysis. Physical form analysis has involved quantification of polymorphism, hydrates, the amorphous form and, recently, protein conformation. Initially, simple powder systems were quantified, although this has since extended to complex pharmaceutical formulations, including tablets, capsules, microspheres and suspensions. Formulations have also been analysed through packaging. The characteristics of the technique make it ideal for process monitoring and it has been used to quantify changes in-situ during processes such as wet granulation and batch crystallisation. The theoretical basis of quantitative Raman spectroscopy, common data analysis approaches, including multivariate analysis, and sources of error in quantitative analysis are also discussed. PMID- 17270073 TI - The influence of various excipients on the conversion kinetics of carbamazepine polymorphs in aqueous suspension. AB - The influence of various excipients on the conversion of carbamazepine polymorphs to the dihydrate in aqueous suspension has been investigated. Ten excipients having functional groups which were potentially able to form hydrogen bonds with carbamazepine (group 1: methylcellulose, hypromellose (hydroxypropyl methylcellulose), hydroxypropylcellulose (HPC), 2-hydroxyethylcellulose (HEC), carmellose sodium (sodium carboxymethylcellulose), cellobiose; group 2: povidone (polyvinylpyrrolidone), povidone-vinyl acetate copolymer (povidone/VA) and N methyl-2-pyrrolidone; group 3: macrogol (polyethylene glycol) and polyethylene oxide-polypropylene oxide copolymer (PEO/PPO)) were selected. Carbamazepine polymorphic forms III and I were dispersed separately into each aqueous excipient solution (0.1%, w/v) for 30 min at room temperature. The inhibition effect of each excipient was quantified using Raman spectroscopy combined with multivariate analyses. The solubility parameter of each excipient was calculated and used for categorizing excipients. Excipients in groups 1 and 2, which had both low solubility parameters (< 27.0 MPa(1/2)) and strong hydrogen bonding groups, inhibited the conversion completely. With increasing solubility parameter, the inhibition effect decreased for group 1 excipients, especially for carbamazepine form I, which had a higher specific surface area. Also, the excipients of group 3, lacking strong hydrogen bonding groups, showed poor inhibition although they had low solubility parameters (< 21.0 MPa(1/2)). This study indicated the importance of both hydrogen bonding interaction and a suitable hydrophobicity (expressed by the solubility parameter) in the inhibition of the conversion of carbamazepine to the dihydrate. PMID- 17270074 TI - Characterization of silicone elastomer vaginal rings containing HIV microbicide TMC120 by Raman spectroscopy. AB - Silicone elastomer vaginal rings are currently being pursued as a controlled release strategy for delivering microbicidal substances for the prevention of heterosexual transmission of HIV. Although it is well established that the distribution of drugs in delivery systems influences the release characteristics, in practice the distribution is often difficult to quantify in-situ. Therefore, the aim of this work was to determine whether Raman spectroscopy might provide a rapid, non-contact means of measuring the concentrations of the lead candidate HIV microbicide TMC120 in a silicone elastomer reservoir-type vaginal ring. Vaginal rings loaded with TMC120 were manufactured and sectioned before either Raman mapping an entire ring cross-section (100 microm resolution) or running line scans at appropriate time intervals up to 30 h after manufacture. The results demonstrated that detectable amounts of TMC120, above the silicone elastomer saturation concentration, could be detected up to 1 mm into the sheath, presumably as a consequence of permeation and subsequent reprecipitation. The extent of permeation was found to be similar in rings manufactured at 25 and 80 degrees C. PMID- 17270076 TI - Applications of solid-state NMR to pharmaceutical polymorphism and related matters. AB - Magic-angle spinning NMR is now making a significant contribution to our understanding of the structure of polymorphs and solvates of pharmaceutical significance. This personal review article discusses a range of applications, with particular emphasis on information about crystallography, for which NMR can address problems that cannot be readily solved by diffraction techniques (such as dynamic disorder and non-stoichiometric hydration). Unlike diffractograms, NMR spectra yield immediate chemical information. Moreover, heterogeneous samples can be investigated and amorphous content provides no significant barrier to studies. Furthermore, NMR can be an effective technique for quantitation (down to the level of ca. 1%). Additional strength is being derived from computation of chemical shifts in solids, using a code that takes account of the spatial repetition inherent in crystalline materials. PMID- 17270075 TI - Terahertz pulsed spectroscopy and imaging in the pharmaceutical setting--a review. AB - Terahertz pulsed spectroscopy (TPS) and terahertz pulsed imaging (TPI) are two novel techniques for the physical characterization of pharmaceutical drug materials and final solid dosage forms, utilizing spectral information in the far infrared region of the electromagnetic spectrum. This review focuses on the development and performance of pharmaceutical applications of terahertz technology compared with other tools for physical characterization. TPS can be used to characterize crystalline properties of drugs and excipients. Different polymorphic forms of a drug can be readily distinguished and quantified. Recent developments towards a better understanding of the fundamental theory behind spectroscopy in the far infrared have been discussed. Applications for TPI include the measurement of coating thickness and uniformity in coated pharmaceutical tablets, structural imaging and 3D chemical imaging of solid dosage forms. PMID- 17270077 TI - Characterization of the bulk properties of pharmaceutical solids using nonlinear optics--a review. AB - With the development of stable, compact and reliable pulsed laser sources the field of characterizing materials through their nonlinear optical response has bloomed. Second harmonic generation by non-centrosymmetric crystal structures has provided a new spectroscopic tool of potentially great utility in the pharmaceutical field. The nonlinear optical response of various materials provides a very sensitive technique for the characterization of pharmaceutically interesting bulk compounds and dispersions, and determining their concentrations. This work has potential application for in-line monitoring and quality control of pharmaceutical manufacturing. In this article we have presented an extensive review of the spectroscopic techniques that make use of the nonlinear optical response of solid media. Also, we have presented the results of our own work in this field. PMID- 17270078 TI - Time-of-flight secondary-ion mass spectrometry for the surface characterization of solid-state pharmaceuticals. AB - Time-of-flight secondary-ion mass spectrometry (ToF-SIMS) is a highly surface sensitive analytical method for surface chemical identification and surface chemical distribution analysis (mapping). Here we have explored the application of ToF-SIMS for the characterization of solid-state pharmaceuticals and highlight specific case studies concerning the distribution and stability of pharmaceutical actives within solid matrices (pellets and polymeric carriers) and the face specific properties of pharmaceutical crystals. PMID- 17270079 TI - A theoretical and spectroscopic study of gamma-crystalline and amorphous indometacin. AB - Amorphous materials are prevalent in the pharmaceutical setting. Whether they are a help or hindrance, their physico-chemical characteristics must be investigated. However, the amorphous form remains a challenge to characterise with many of its properties poorly understood. In this study, gamma-crystalline and amorphous indometacin are investigated using vibrational spectroscopy and quantum chemical calculations. The structure of the single indometacin molecule and the dimer in the gamma-form were optimised using density functional theory calculations. The optimised structures were similar to the conformations in the crystal form, suggesting that conformation of the molecules in the crystal may be close to the average molecular structure in less-ordered states. Infrared and Raman spectra were calculated from the optimised structures. Many modes in the calculated spectra could be matched with the experimental spectra of the gamma-crystalline and amorphous forms, and a description of the matched modes has been provided. By analysis of the theoretical vibrational modes it was confirmed that the amorphous form of indometacin produced by quench cooling the melt consists predominantly of dimers, similar in structure to in the gamma-crystalline form. In addition, differences in intermolecular bonding between the two forms were identified. Quantum mechanical calculations allow improved understanding of amorphous materials and their vibrational spectra. PMID- 17270080 TI - The use of quantum chemistry in pharmaceutical research as illustrated by case studies of indometacin and carbamazepine. AB - A number of case studies that illustrate how quantum chemistry may be used in studying pharmaceutical systems are reviewed. A brief introduction to quantum methods is provided and the use of these methods in understanding the structure and properties of indometacin and carbamazepine is discussed. The use of calculated structures and molecular electrostatic potentials in developing quantitative structure-activity relationships is discussed along with the use of computation chemistry to predict spectroscopic properties. PMID- 17270081 TI - 2-Ethylhexyl-2,4,5-trimethoxycinnamate and di-(2-ethylhexyl)-2,4,5 trimethoxybenzalmalonate as novel UVA filters. AB - A series of 2-ethylhexylmethoxy substituted cinnamates and benzalmalonates have been synthesized and characterized. 2-Ethylhexyl-2,4,5-trimethoxycinnamate (E8) and di-(2-ethylhexyl)-2,4,5trimethoxybenzalmalonate (B8) show UVA absorption with high molar absorption coefficients (12000-14 000 cm(-1) M(-1) at 350 nm). E8 undergoes trans to cis photoisomerization under UVA exposure causing the decrease in UV absorption efficiency. E8 is more photostable than butyl methoxy dibenzoylmethane (BMDBM). For example, 41.64 J cm(-2) UVA irradiation produces 20+/-2% and 25+/-2% loss in UV absorption for E8 and BMDBM, respectively. Similar irradiation produces no change in the UV absorption of B8. Both the oily liquid E8 and the yellow solid B8 can be dissolved in various organic solvents, ranging from methanol to hexane, various silicone fluids and 2-ethyl-hexyl-4 trimethoxycinnamate (EHMC, a widely used UVB filter). A liquid broadband filter comprising B8 and EHMC shows excellent photostability in both UVB and UVA regions. PMID- 17270082 TI - Gastroprotective and cytotoxic effect of semisynthetic ferruginol derivatives. AB - The gastroprotective abietane diterpene ferruginol has been shown to present high cytotoxicity. In order to obtain active compounds with less cytotoxicity, 18 semisynthetic ferruginol derivatives and totarol were assessed for their gastroprotective effects in the HCl/ethanol-induced gastric lesion model in mice, as well as for cytotoxicity in human gastric epithelial cells (AGS) and human lung fibroblasts (MRC-5). At 20 mg kg(-1), the greatest gastroprotective effects were provided by abieta-8,11,13-triene (1), abieta-8,11,13-trien-12-yl-2 chloropropanoate (8), abieta-8,11,13-trien-12-yl propenoate (9), 12-(2,3,4,6 tetra-O-acetyl-beta-D-glucopyranosyloxy)-abieta-8,11,13-triene (17) and 12-(beta D-galactopyranosyloxy)-abieta-8,11,13-triene (18), all of which were as active as the reference drug lansoprazole at 20 mg kg(-1), reducing gastric lesions by 69, 76, 67, 72 and 61%, respectively. No relation was observed between lipophilicity and the gastroprotective effect. Compounds that showed the greatest cytotoxicity towards AGS cells were ferruginol (2), the corresponding formate (5), acetate (6), propionate (7), 8, 9, 12-(beta-D-glucopyranosyloxy)-abieta-8,11,13-triene (16), 18 and totarol (20) (IC50 18-44 microM). Ferruginol and compounds 5-9, 16, 18 and 20 were the most toxic compounds against fibroblasts (IC50 19-56 microM), with a correlation to AGS cells. The derivative 19 was much more active against AGS cells than towards fibroblasts. The best activity/cytotoxicity ratio was found for compound 17, with a lesion index comparable with lansoprazole at 20 mg kg(-1) and cytotoxicity >1000 microM towards MRC-5 and AGS cells, respectively. In conclusion, some derivatives showed a better gastroprotective effect/cytotoxicity ratio than the parent compound ferruginol. A total of 13 new compounds are reported here for the first time. PMID- 17270083 TI - Ameliorating effects of essential oil from Acori graminei rhizoma on learning and memory in aged rats and mice. AB - Although there are normal cognitive changes that take place as a person becomes older, ageing in humans is generally associated with a deterioration of cognitive performance, in particular of learning and memory. There are a number of herbal medicines that are reported to improve brain function and intelligence. In the present study, the ameliorating effects of an essential oil extracted from Acori graminei rhizoma on learning and memory in aged, dysmnesia rats and mice were determined using the step-down passive avoidance test and Y maze. Oral administration of the essential oil (0.02, 0.04 and 0.08 g kg(-1)) to rats for 30 days and to mice for 15 days improved the latency and number of errors in aged, dysmnesia rats and mice. The cerebral neurotransmitters in aged rats given the essential oil (0.02, 0.04, 0.08 g kg(-1)) for 30 days were also investigated, and increased levels of norepinephrine, dopamine and serotonin, and decreased levels of acetylcholinesterase activity were found. The results suggest that the essential oil improves cognitive function in aged animals possibly by increasing norepinephrine, dopamine and serotonin relative levels, and by decreasing the activity of acetylcholinesterase in the cerebra. PMID- 17270085 TI - Parathyroid hormone, kidney disease, evidence and guidelines. PMID- 17270084 TI - Biocompatibility of polypyrrole particles: an in-vivo study in mice. AB - The objectives of this study were the chemical synthesis of polypyrrole particles, the investigation and estimation of the impact of polypyrrole particle concentration, and the evaluation of the effect of duration of treatment on immune-related haematological parameters and peritoneum cells in mice. The results showed that chemically prepared polypyrrole particles did not have any detectable cytotoxic effect on mouse peritoneum cells. Polypyrrole particles did not induce any allergic response, nor did they affect spleen, kidney or liver indexes. Moreover, no effect of polypyrrole particles on immune-related haematological parameters was observed. No inflammation was detected in the peritoneum of mice after a 6-week period of treatment with polypyrrole particles. In conclusion, chemically synthesized polypyrrole particles showed good biocompatibility in mice and are attractive candidates for biomedical applications in-vivo. PMID- 17270086 TI - Measurement of serum testosterone in women; what should we do? AB - All immunoassays for female serum testosterone give falsely high results in some samples. The effect is variable and cannot be predicted for any given sample. Inaccurate calibration or interference by cross-reacting substances is almost certainly the cause of the problem, but for many immunoassays, the exact nature of the interferent is not known. Some of the interference can be removed by employing an extraction step prior to immunoassay. The advent of fast simple and sensitive liquid chromatography tandem mass spectrometry methods offers an exciting alternative to immunoassay for serum testosterone measurement. It is recommended that all high serum testosterone concentrations in women are checked, before reporting, by a method which is accurate (i.e. minimal bias to isotope dilution gas chromatography mass spectrometry [ID-GCMS] method) and is not subject to interference. Action should also be taken by assay users, manufacturers, regulators and professional bodies to ensure accurate standardization and comparability of assays. PMID- 17270087 TI - Creatinine and glomerular filtration rate: evolution of an accommodation. AB - This brief review examines the history of the use of creatinine as a measure of renal function. While there are more accurate markers of glomerular filtration, creatinine was chosen for convenience. Since the relationship of creatinine to glomerular filtration depends upon a tenuous balance of counterbalancing factors, practitioners should be alert to situations that alter that balance. While the averaging of variations over time helps to avoid some of the problems with diurnal variations in the past, the present-day reliance upon equations based upon a solitary serum value is likely to amplify those problems in clinical situations when the effect of disease, medications, diet and time of day upon that balance are not considered. PMID- 17270088 TI - The sweat test for the diagnosis of cystic fibrosis--a personal experience of guideline production. AB - The need for evidence-based guidelines as to how to conduct the sweat test in the UK was highlighted in 2000 by the National External Quality Assessment Scheme Specialist Advisory Committee. A Guideline Group supported by several professional bodies was subsequently convened and formal evidence-based guidelines were produced and published in 2003. The process of undertaking guideline production is summarized here, together with the author's personal opinions about the experience and highlights of the shortcomings and lessons learnt from the project. In summary, production of evidence-based guidelines is a long process and is only worth the effort (both man hours and financial) if the recommendations are subsequently adopted into clinical practice and in turn improve patient care. The emphasis for the future should be to assess the impact and value of evidence-based guidelines and promote their introduction into local practice as part of care pathways. A growing number of guideline initiatives emphasizes the importance of and a need for an overarching coordinating structure to overcome problems of duplication and enable interested professionals from different disciplines to work on related initiatives. PMID- 17270089 TI - Guidelines for the performance of the sweat test for the diagnosis of cystic fibrosis. AB - A multidisciplinary group (representing various professional bodies and supported by the Cystic Fibrosis Trust) has developed evidence-based guidelines for the performance of the sweat test in the UK. The guidelines cover patient information, subject suitability, sweat collection, sweat analysis, quality, interpretation of results, and responsibility for testing and training. The guidelines were produced following a detailed literature search by the process described by the Royal College of Paediatrics and Child Health (RCPCH), using the Scottish Intercollegiate Guidelines Network 1 (SIGN 1) criteria to grade the evidence. Recommendations are graded A, B, or C, depending on the level of evidence. The grade B recommendations (there were no grade A recommendations) were subsequently appraised and endorsed as part of the RCPCH process, according to Appraisal of Guidelines for Research and Evaluation in Europe (AGREE). The recommendations are summarized in tabular form representing the final version incorporating the comments from the appraisal process. Both the appraisal comments and the full evidence base can be found on www.rcpch.ac.uk/publications/clinical_docs.html. The full guidelines can also be found on http://www.ukneqas.org.uk/guidelines.htm. PMID- 17270090 TI - The influence of a cooked-meat meal on estimated glomerular filtration rate. AB - BACKGROUND: Chronic kidney disease (CKD) is an important but under-recognized condition. Recent national guidelines have recommended that biochemistry laboratories report estimated GFR (eGFR) to improve diagnosis of CKD and facilitate disease staging and management. Previous reports have suggested that intake of large amounts of cooked meat can lead to a significant increase in serum creatinine concentration. METHODS: Participants (n = 32), consisting of 17 healthy volunteers and 15 outpatients, were recruited. Measurement of serum creatinine (kinetic Jaffe method, enzymatic, isotope-dilution mass spectrometry [IDMS]) and cystatin C, and calculation of eGFR were carried out before (i) and after a meal containing cooked meat (ii) and a meat-free meal (iii). RESULTS: Following intake of cooked meat, median serum creatinine concentration (kinetic Jaffe) increased from 80.5 micromol/L preprandially to 101.0 micromol/L 1-2 h postprandially (P<0.0001), and 99.0 micromol/L 3-4 h postprandially (P<0.0001). Median eGFR decreased from 84.0 mL/min/1.73 m2 preprandially to 59.5 mL/min/1.73 m2 1-2 h postprandially (P<0.0001), and 64.0 mL/min/1.73 m2 3-4 h postprandially (P<0.0001). Consumption of non-meat-containing meals had little impact on serum creatinine (kinetic Jaffe) and eGFR. Changes in serum creatinine were similar using all three methods, and cystatin C concentration was generally uninfluenced by food intake. CONCLUSIONS: Intake of cooked meat has a significant effect on serum creatinine concentration and eGFR. Misclassification of CKD is possible if measurements are made after meals containing cooked meat. Clinicians should ensure that CKD classification is based on samples taken in the appropriate conditions: either fasting or after avoidance of cooked meat on the day of sampling. National guidelines which overlook this factor should be revisited. PMID- 17270091 TI - Oxidative and nitrosative stress in acute ischaemic stroke. AB - BACKGROUND: Increased nitric oxide (NO) production may result in further brain damage via nitric oxide synthase uncoupling in patients with acute ischaemic stroke by increasing free radical formation and oxidative stress. In this connection, we measured nitrite and nitrate (NO metabolites), ischaemia-modified albumin (IMA) and thiobarbituric acid-reactive substances (TBARS) in patients with ischaemic stroke. METHODS: We studied 41 patients with ischaemic stroke (22 men and 19 women, aged 65+/-13 years) and 37 age- and sex-matched controls (22 men and 15 women, aged 65+/-8 years). Blood samples were drawn within the first 24 h from the onset of symptoms in the patient group. Fasting morning samples were used in the control group. Concentrations of nitrite and nitrate were determined by Griess reagent; concentrations of IMA were determined by the albumin cobalt-binding test; and concentrations of TBARS were determined colorimetrically by thiobarbituric acid. RESULTS: Nitrate, IMA and TBARS concentrations were significantly increased compared with controls (P<0.005, P<0.001, and P=0.01, respectively). CONCLUSIONS: Patients with acute ischaemic stroke exhibit abnormalities in a range of markers of increased nitrosative and oxidative stress. These abnormalities may contribute to greater brain damage in patients with acute ischaemic stress. PMID- 17270092 TI - Simultaneous determination of androstenedione and testosterone in human serum by liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: We aimed to develop a sensitive assay to quantitate serum concentrations of both androstenedione and testosterone within the female range simultaneously, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for use in the routine clinical laboratory and to compare this method with immunoassay. METHOD: Samples (200 microL) were prepared by liquid-liquid extraction using (1 mL) methyl-tert-butyl-ether. Deuterated androstenedione and testosterone were used as internal standards. RESULTS: The standard curve was linear to 50 nmol/L, the lower limit of quantitation was 0.25 nmol/L, and intra- and inter-assay coefficients of variation were < 10% for both androgens over the range 0.3-35 nmol/L. There was a poor relationship between the LC-MS/MS and the radioimmunoassay methods for androstenedione with the LC-MS/MS generally giving lower results. For testosterone, the LC-MS/MS and immunoassay methods compared well at all concentrations. However, when female samples only were examined, the agreement deteriorated. CONCLUSIONS: We have developed a sensitive and precise LC MS/MS method, which gives more accurate results for all androstenedione measurements and low testosterone concentrations than immunoassay. PMID- 17270093 TI - Autoantibodies against tumour suppressor protein p53 in pleural effusions of patients with tuberculosis pleurisy. AB - BACKGROUND: Autoantibodies against the p53 proteins (p53 Abs) can be detected in the serum, ascites, saliva and pleural effusions of various malignant patients. It is suggested that p53 Abs in pleural effusions might have some value for tumour diagnosis, prognosis or monitoring. The present study investigated the prevalence of p53 Abs in the pleural effusions of 90 patients with various diseases. METHODS: Patients with suspicious pleural effusions in chest film received thoracocentesis and their pleural effusions were collected. The presence of p53 Abs in effusion was detected by immunoblotting. Differences of p53 Abs with respect to the patient's age, gender, white blood cell count, lactate dehydrogenase, total proteins and adenosine deaminase scores were calculated by chi2-test. RESULTS: p53 Abs were detected in 14.4% (13/90) of our patients, with prevalences of 10.5% (6/57) and 21.2% (7/33) among patients with benign and malignant diseases, respectively. Notably, 16.1% (5/31) of patients with tuberculosis pleurisy were positive for p53 Abs. These five patients had no history of cancer and, so far, have had no manifestations related to tumorigenesis. CONCLUSIONS: As far as we know, this is the first report regarding the detection of p53 Abs in pleural effusions from patients with tuberculosis pleurisy. PMID- 17270095 TI - Elevated serum dipeptidyl peptidase IV activity in patients with chronic tonsillitis. AB - BACKGROUND: Palatine tonsils represent the first place of contact for a variety of antigenic substances present in air and food. Upon antigen stimulation, the interactions between T and B lymphocytes in the tonsil are known to depend on the expression of different co-stimulatory molecules, including proteolytic ectoenzymes. Dipeptidyl peptidase IV (DPP IV) and aminopeptidase N (APN), as T lymphocyte co-stimulatory molecules, participate in the regulation of the immune response during inflammation. METHODS: In this study, the serum and lymphocyte enzymatic activity of DPP IV and APN was investigated in 32 patients, 13 with recurrent tonsillitis (RT) and 19 with tonsillar hypertrophy (TH), before and one month after tonsillectomy. The enzymatic activity of DPP IV and APN in tonsillar lymphocytes and serum was determined kinetically at 37 degrees C using Gly-Pro-p nitroanilide (for DPP IV) and Ala-p-nitroanilide (for APN) as chromogenic substrates. RESULTS: Significantly higher serum DPP IV and APN activities (P<0.001) were found in TH patients compared with those with RT before tonsillectomy. DPP IV activity in TH patients was also elevated compared with the control of the same age (P<0.001), whereas the activity of APN was the same as the control group. The activity of both enzymes was the same as of controls after tonsillectomy. In addition, the results show that DPP IV and APN activities in serum decrease significantly with age. Tonsillar lymphocytes demonstrated a wide range of DPP IV and APN activities without significant differences between the investigated groups. CONCLUSION: An increased serum DPP IV activity was observed in TH patients compared with both RT patients and controls before tonsillectomy. After tonsillectomy, all activities were similar. The results suggest that serum DPP IV activity may have potential as a diagnostic marker for patients with TH. PMID- 17270094 TI - Steatosis and hepatic markers before and shortly after bariatric surgery. AB - BACKGROUND: We present new findings on liver steatosis detected in a group of 20 morbidly obese patients who were reassessed shortly after bariatric surgery (BS) by assaying hepatic markers in their serum. METHODS: We assayed aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyl transferase (gamma-GT), cholinesterase, cholesterol, total protein, and albumin, and measured the weight and the body mass index (BMI) of patients, before and one and three months after surgery. RESULTS: There were significant reductions in BMI following surgery and also falls in transaminases and gamma-GT activities three months after BS. No changes occurred in other parameters between periods, except that cholesterol was above reference values before BS and fell to normal levels three months after BS. CONCLUSIONS: We suggest that before undergoing surgery, the patients suffered from slight steatosis, while after BS the reduction in AST and gamma-GT indicated that this condition was corrected within three months. Moreover, these enzymes may be useful markers for excess fat in the liver. PMID- 17270096 TI - Laboratory testing for C1 inhibitor deficiency: a comparison of two approaches to C1 inhibitor function. AB - BACKGROUND: C1 inhibitor deficiency may be hereditary or acquired. It is characterized by absent or poorly functioning C1 inhibitor. The disorder is rare, with prevalence estimated at 1/50,000. The very low incidence of the condition makes the sensitivity and specificity of assays used particularly important. Two different methods are commercially available to measure C1 inhibitor function. There are few data comparing these assays. METHODS: Two assays of C1 inhibitor function (C1 inhibitor-C1s complex formation or inhibition of C1 esterase cleavage of artificial substrate [colorimetric]) were compared in 71 patients (28 hereditary angioedema, 2 acquired angioedema and 41 controls). RESULTS: Qualitatively, the two assays showed good correspondence (92%). Six of 71 results were discordant. Correlation in quantitative terms was moderate (R = 0.81). CONCLUSIONS: Both assays show high sensitivity for hereditary/acquired angioedema. The colorimetric assay is more prone to false-positive results. However, clinical interpretation is not adversely affected. PMID- 17270097 TI - Effect of albumin concentration on serum cortisol measured by the Bayer Advia Centaur assay. AB - INTRODUCTION: A poor comparison was seen between the Bayer Advia Centaur and the Roche Elecsys cortisol methods using samples sent to the laboratory for cortisol analysis. They were predominantly from patients attending the Endocrine outpatients clinic or patients in the intensive therapy unit. We investigated the effect of albumin concentration on the performance of both assays. METHODS: For the samples used in the patient comparison, the laboratory database was searched for any concomitant albumin concentrations (Beckman LX20 BCP method). A series of recovery experiments were performed combining samples with normal albumin and undetectable cortisol concentrations with samples with detectable cortisol but low albumin concentrations. RESULTS: Albumin concentration accounts for almost 50% of the variation in the difference between the two methods. The Bayer Advia Centaur method shows significant under-recovery at albumin concentrations lower than 24 g/L. CONCLUSION: This under-recovery will significantly affect the diagnosis of adrenal insufficiency in critically ill patients with low albumin concentrations. PMID- 17270098 TI - The angiotensin II type 2 receptor gene polymorphism and body mass index in healthy Japanese women. AB - BACKGROUND: Angiotensin II (AngII), through the AngII type 2 receptor (AT2-R), might exert some effect on adipocyte- and lipogenesis-related biology. The Adenine/Cytosine 3123 (A/C(3123)) polymorphism in the AT2-R gene is reportedly involved in some diseases, such as hypertension. METHODS: A total of 201 healthy Japanese women (mean age 43.2 years) were enrolled in the study to investigate the association among the AT2-R A/C(3123) polymorphism detected by polymerase chain reaction methods, body mass index (BMI) and other obesity-linked metabolic parameters (blood pressure, serum lipid/lipoprotein, plasma glucose). RESULTS: Homozygotes of the C-allele in the AT2-R A/C(3123) polymorphism were associated with small but significant increases in BMI levels. There were no differences between genotype-based groups in the obesity-linked metabolic parameters. CONCLUSION: These findings suggest that the AT2-R A/C(3123) polymorphism could be a polymorphic marker related to BMI in Japanese women. PMID- 17270099 TI - Evidence of cardiomyocyte necrosis in glycogen storage disease type II. AB - Adult-onset glycogen storage disease type II (GSD-II), unlike the infantile form, is not normally associated with coexisting cardiovascular pathologies. In infantile onset GSD-II, cardiomyopathy is a common feature, and mutations in the genes for cardiac troponin T and I are likely to be involved. This case report describes a 39-year-old man with no classical risk factors for premature cardiac disease who presented with central chest pain and shortness of breath. Serum aspartate transaminase (AST) had been consistently elevated for 15 years. Adult GSD-II had been diagnosed two years previously by muscle biopsy. On presentation, there was an elevated serum creatine kinase and AST. Electrocardiography and echocardiography were both normal, and an acute coronary syndrome was ruled out. Cardiac Troponin T (cTnT) was found to be positive at 0.1 microg/L using a Cardiac Reader, subsequently confirmed on an Elecsys 1010 (both from Roche Diagnostics, Lewes, UK). cTnT may therefore be a useful biomarker in examining subclinical cardiac involvement in GSD-II patients. PMID- 17270100 TI - Silent growth hormone secreting pituitary adenomas: IGF-1 is not sufficient to exclude growth hormone excess. AB - Circulating insulin-like growth factor-1 (IGF-1) is increasingly being used as a screening test and in ongoing monitoring of treated acromegaly. We here present three cases of women (two of whom were on the oestrogen containing contraceptive pill at the time of presentation) who had normal circulating IGF-1 and no overt clinical features of acromegaly at the time of their pituitary surgery. Postoperatively, all were confirmed to have growth hormone excess in keeping with the presence of active somatotroph pituitary adenomas. We suggest that for optimal patient management, formal evaluation of growth hormone status with oral glucose tolerance testing should ideally be performed on all individuals for whom pituitary surgery is planned. PMID- 17270101 TI - Reliability of 6-h troponin T remains unproven. PMID- 17270102 TI - Thyrotoxicosis with hypokalaemic paralysis and hyperlactataemia. PMID- 17270105 TI - A toddler with failure to thrive and impaired vision. PMID- 17270106 TI - HPV vaccine and its recommendations, 2007. AB - Quadrivalent human papillomavirus vaccine against the viral types most likely to cause cervical cancer (types 16 and 18) and genital warts (types 6 and 11) has been licensed in the United States. The vaccine is 95% to 100% efficacious against cervical intraepithelial neoplasia and adenocarcinoma in situ and 99% efficacious against genital warts caused by serotypes in the vaccine. Local pain injection site pain and swelling are the main adverse reactions. Routine vaccination of females at 11 to 12 years of age is recommended. Catch-up vaccination is recommended for females age 13 to 26 years who have not yet been vaccinated, and vaccination of girls 9 and 10 years of age is permitted at the discretion of the physician. PMID- 17270107 TI - Recent changes in influenza vaccination recommendations, 2007. AB - Influenza disease continues to cause thousands of deaths in the United States. Due to the burden of influenza hospitalizations among children, inactivated influenza vaccine is now routinely recommended for children age 6 to 59 months. Live attenuated influenza vaccine is available for healthy persons 5 to 49 years of age. Other recent developments include routine vaccination of pregnant women with inactivated vaccine and an emphasis on the vaccination of health care workers. PMID- 17270108 TI - Routine vaccines across the life span, 2007. AB - Routine vaccines are listed on the Recommended Childhood and Adolescent Immunization Schedule and the Recommended Adult Immunization Schedule published by the Centers for Disease Control and Prevention and reviewed and updated by the Advisory Committee on Immunization Practices. For these vaccines, we discuss the disease burden, rationale for vaccination, efficacy, adverse reactions, and recommendations. Some new vaccines are discussed here (Tdap and zoster), whereas others (rotavirus and human papillomavirus) are discussed elsewhere in the supplement. PMID- 17270109 TI - Vaccines for persons at high risk, 2007. AB - Morbidity and mortality due to vaccine-preventable diseases are high among persons with underlying medical conditions. Thus, inactivated influenza and pneumococcal polysaccharide vaccines are recommended for individuals with cardiac disease, diabetes mellitus, chronic obstructive pulmonary disease, immunosuppression, and other chronic illnesses. Inactivated influenza vaccine is recommended for pregnant women and for persons with asthma and neuromuscular disease. Palivizumab, a respiratory syncytial virus immunoglobulin preparation, is recommended for certain infants with prematurity and chronic lung disease. Health care workers are at high risk for acquiring and transmitting hepatitis B, pertussis, measles, varicella, and influenza; hence, vaccination against these diseases is recommended. A signed declination is recommended for health care workers who refuse influenza vaccination. PMID- 17270110 TI - Vaccine schedules and procedures, 2007. AB - This article reviews the 2007 recommended childhood and adolescent immunization schedules; the catch-up immunization schedules for children and adolescents; the 2006-2007 recommended adult immunization schedule; recommended and minimum ages and intervals between vaccine doses; contraindications for immunization; and general guidelines on immunization procedures. With the exception of some formulations of influenza vaccines, all recommended childhood vaccines are thimerosal-free. Since 2005, changes in vaccine schedules affect the following vaccinations: hepatitis A, rotavirus, human papillomavirus, varicella, meningococcal, adult tetanus and diphtheria toxoids and acellular pertussis, and influenza. Minimal intervals between vaccines and vaccine precautions, contraindications, administration, and storage are reviewed. Sources of up-to date vaccine information are presented. PMID- 17270111 TI - Rotavirus: disease and vaccine update, 2007. AB - Rotavirus infection is a ubiquitous illness, infecting the vast majority of children worldwide in the first 5 years of life. Rotavirus is one of the major causes of severe diarrhea in infants and young children throughout the developing and developed world. An estimated 500,000 deaths per year occur, with the burden of morbidity and mortality highest in the poorest nations. Two new oral, live, attenuated vaccines have recently shown efficacy and safety in clinical trials, and one of these, RotaTeq, was approved by the US Food and Drug Administration on February 3, 2006. RotaTeq is recommended for general use by the Centers for Disease Control and Prevention, American Academy of Family Practice, and American Academy of Pediatrics. PMID- 17270112 TI - Addressing immunization barriers, benefits, and risks. AB - Vaccines have been highly effective in eliminating or significantly decreasing the occurrence of many once-common diseases. Barriers to immunization are a significant factor in the rising incidence rates of some vaccine-preventable diseases. Cost, reduced accessibility to immunizations, increasingly complex childhood and adolescent/adult immunization schedules, and increasing focus on the potential adverse effects of vaccines all contribute to difficulty in meeting the 2010 immunization goals. Physicians must not only be knowledgeable about vaccines but they must incorporate systems in their offices to record, remind, and recall patients for vaccinations. They must also clearly communicate vaccine benefits and risks while understanding those factors that affect an individual's acceptance and perception of those benefits and risks. PMID- 17270114 TI - Targeted treatment strategies for menstrual migraine. PMID- 17270113 TI - Adjuvant analgesics for the treatment of neuropathic pain: evaluating efficacy and safety profiles. PMID- 17270115 TI - Use of opioids. PMID- 17270116 TI - Dysglycemia and fluoroquinolones: are you putting patients at risk? PMID- 17270117 TI - Neck mass: how would you treat? PMID- 17270118 TI - Itchy rash near the navel. PMID- 17270119 TI - Piercing among adolescents: body art as risk marker. PMID- 17270120 TI - Clinical inquiries. Do inhaled steroids increase the risk of osteoporosis? PMID- 17270121 TI - Clinical inquiries. What is the preferred treatment for a child with mild persistent asthma? PMID- 17270122 TI - Clinical inquiries. Do topical antibiotics improve wound healing? PMID- 17270123 TI - Clinical inquiries. Angiotensin blockade for diabetes: monitor microalbuminuria? PMID- 17270124 TI - Clinical inquiries. What evaluation is best for an isolated, enlarged cervical lymph node? PMID- 17270125 TI - Clinical inquiries. What is the best treatment for hypertension in African Americans? PMID- 17270128 TI - Establishment of the human coagulation factor VII concentrate European Pharmacopoeia biological reference preparation batch 1. AB - For the potency assay of human coagulation factor VII concentrate preparations according to the European Pharmacopoeia (Ph. Eur.) a reference preparation calibrated in International Units (IU) is needed. Currently, the 1st International Standard (97/592, potency: 6.3 IU/ampoule) but no Ph. Eur. reference preparation is available. A collaborative study was run to calibrate a candidate Ph. Eur. Biological Reference Preparation (BRP) for human coagulation factor VII concentrate against the 1st International Standard; the BRP is intended to be used as working standard. A candidate BRP batch 1 was produced from a plasma-derived human factor VII concentrate preparation available on the European market. It fulfilled the requirements of a BRP with regard to precision and homogeneity of fill, residual water content and stability. In addition, the content of activated factor VII was low. Sixteen laboratories from 9 countries participated in the collaborative study. The potency of the candidate BRP was determined using the participants' chromogenic assay based on the Ph. Eur. and their in-house clotting assay, if available. The statistical model used for analysis of the results from most laboratories was the maximum likelihood of the parallel line model following a logarithmic transformation of the responses. In the chromogenic assay, a potency estimate of 8.2 IU/vial (+/-3.7%) was obtained for the candidate BRP. Results from the clotting assay were lower and less homogenous (6.7 IU/vial+/-11.6%). The results from the collaborative study showed that the candidate BRP is suitable as a reference standard for the chromogenic assay according to the Ph. Eur. It was adopted by the Ph. Eur. Commission in March 2006 as official Ph. Eur. BRP for this purpose. PMID- 17270127 TI - Validation of a new ELISA method for in vitro potency assay of hepatitis B containing vaccines. AB - The discontinuation of the Auszyme kit used by vaccine manufacturers and national control laboratories to determine the Hepatitis B surface antigen (HBsAg) content of hepatitis B vaccines has led GlaxoSmithKline (GSK) to develop an alternative inhibition ELISA method. Validation of this ELISA was performed according to The International Conference of Harmonization and reproducibility was assessed in a feasibility study with four Official Medicines Control Laboratories (OMCLs). The dose response curve demonstrated linearity (R2>0.99) in the range of 60-360 ng/ml HBsAg. The repeatability (CV<7%), intermediate precision (CV<10%) and accuracy (91-113% recovery) were similar to the Auszyme method. The commercial antibodies used in the assay were shown to contain antibodies that bind to a protective epitope of HBsAg and the specificity of the method for HBsAg was demonstrated. There was a good concordance with the Auszyme method, although the ELISA yielded higher results (25.3 vs. 24.4 micro.g/ml for Engerix-B (n=64), 28.9 vs. 27.0 micro.g/ml for Twinrix (n= 69) and 25.5 vs. 21.6 micro.g/ml for Infanrix penta (n=62)). The method was successfully transferred to the four OMCLs. It has been demonstrated that the ELISA is suitable for its intended purpose with hepatitis B containing vaccines from GSK and thus could be used for these vaccines by national control laboratories and authorities. Further validation studies should focus on the use of this ELISA with vaccines from other manufacturers. PMID- 17270126 TI - Validation of in vitro potency assays for tetanus immunoglobulin. AB - The European Pharmacopoeia (Ph. Eur.) monograph Human tetanus immunoglobulin (0398) gives a clear outline of the in vivo assay to be performed to determine the potency of human tetanus immunoglobulins during their development. Furthermore, it states that an in vitro method shall be validated for the potency estimation. Since no further guidance is given on the in vitro assay, every control laboratory concerned is free to design and validate an in-house method. At the moment there is no agreed method available. The aim of this study was to validate and compare 2 alternative in vitro assays, i.e. an enzyme-linked immunoassay (EIA) and a toxoid inhibition assay (TIA). The potency of 2 tetanus immunoglobulin preparations (Product 1, Product 2) was estimated against the WHO International Standard for tetanus immunoglobulin, using the tetanus EIA and TIA. The coefficient of variation (CV) to characterise the assay precision was 3.2% (EIA) and 3.6% (TIA), and the corresponding CV for intra-assay variation was 4.7% (EIA) and 5.5% (TIA). Using a spiking procedure, the 2nd part of the experiment investigated recovery of a known anti-tetanus potency. The recovery of samples spiked with defined amounts of reference preparation ranged from 104 112% (EIA) and 114 125% (TIA) respectively, resulting in a mean bias of 2.2 IU/ml (95% confidence interval (CI): -1.1-5.4 IU/ml, EIA) and 5.8 IU/ml (95% CI: 1.4 10.2 IU/ml, TIA). Good agreement was observed between the in vivo and in vitro assay results: the relative potency results of the EIA and TIA as compared to those of the in vivo assay performed by the manufacturers of the 2 tetanus immunoglobulins were for the EIA in the range of 104+/-10% for Product 1 and 100+/-6% for Product 2, and for the TIA in the range of 107+/-6% for Product 1 and 100+/-7% for Product 2. Tetanus EIA and TIA are suitable quality control methods for polyclonal tetanus immunoglobulin, which can be standardised in a quality control laboratory using a quality assurance system. In a collaborative study it will now be evaluated whether the validated methods can be proposed as common in vitro batch potency assays for replacement of the in vivo mouse assay. PMID- 17270129 TI - Collaborative study for the establishment of replacement batches for somatropin CRS batch 1. AB - A project was run for the establishment of replacement batches of the European Pharmacopoeia (Ph. Eur.) Somatropin Chemical Reference Substance (CRS) batch 1. Twenty two laboratories from 16 countries took part in a collaborative study aimed at demonstrating the suitability of the candidate reference preparations to serve as working references in the tests for identification by peptide mapping and capillary electrophoresis (CE); related proteins, dimers and related substances of higher molecular mass; charged variants distribution; and/or for the assay of somatropin, as performed in accordance with the specifications of the current Ph. Eur. monographs 0950 Somatropin bulk solution, 0951 Somatropin and 0952 Somatropin for injection. Further to the completion of the study the Ph. Eur. Commission adopted one candidate in March 2006 as somatropin CRS batch 2 (with an assigned content of 1.69 mg somatropin monomer per vial) and the second one in June 2006 as somatropin/desamidosomatropin resolution mixture CRS batch 1 (prescribed use of the latter standard is restricted to the test for related proteins). PMID- 17270130 TI - Collaborative study to establish human immunoglobulin BRP batch 3 and human immunoglobulin (molecular size) BRP batch 1. AB - A study was carried out by the European Directorate for the Quality of Medicines (EDQM) as part of the joint Biological Standardisation Programme of the Council of Europe and the European Commission with the aim to establish replacement batches of the European Pharmacopoeia (Ph. Eur.) human immunoglobulin Biological Reference Preparation (BRP) batch 2. Twenty-eight laboratories participated in this study. The suitability of the candidate reference preparations to serve as working references in the tests for distribution of the molecular size, anticomplementary activity and Fc function, in accordance with the specifications of the Ph. Eur. monographs Human normal immunoglobulin for intravenous administration (0918), Human normal immunoglobulin (0338) and Anti-T lymphocyte immunoglobulin for human use, animal (1928) was demonstrated. The candidates were therefore established as human immunoglobulin BRP batch 3 and Human immunoglobulin (molecular size) BRP batch 1. The prescribed use of the latter BRP is limited to the test for distribution of molecular size. PMID- 17270132 TI - Establishment of European pharmacopoeia Mycoplasma reference strains. AB - European Pharmacopoeia (Ph. Eur.) general chapter 2.6.7. Mycoplasma requires for the culture test reference strains of mycoplasma field isolates with fewer than 15 passages for validation and run control and in the test for inhibitory substances. Low passage field isolates of 5 mycoplasma strains (Mycoplasma hyorhinis, Mycoplasma synoviae, Mycoplasma fermentans, Mycoplasma orale and Acholeplasma laidlawii) have been prepared for this purpose and a small scale collaborative study involving European laboratories was carried out to confirm the suitability of the material for the intended purpose. Strains were prepared as 1 ml samples in frozen format and are stored below -60 degrees C. Each laboratory determined a titre for the material on their in-house media. A secondary part of the study also compared the growth of prediluted samples on the different culture media. Results of the study confirm that the material is suitable for use as a biological reference preparation (BRP) and an estimated titre has been provided for each strain based on the results of the study. It was noted that differences in the culture media used in the different laboratories did not have a detrimental effect on titre estimation. The estimated titre is intended as a guide for users to validate the use of the reference material in house. The candidate BRPs were adopted by the European Pharmacopoeia Commission on June 28, 2006 and are available for use from EDQM. A revision to chapter 2.6.7, including reference to the use of nucleic acid amplification techniques (NAT) was also adopted in June 2006 and will appear in the European Pharmacopoeia version 5.8 in January 2007 and come into force the 1st of July 2007. While it was not part of the study a number of participants also performed in-house NAT assays on the study material. Preliminary findings from these studies are presented. PMID- 17270131 TI - International collaborative study to establish immunoglobulin (anti-D test) BRP batch 1. AB - An international collaborative study was organised to establish a European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) and United States (US) Food and Drug Administration (FDA) reference preparation for the test for anti-D (anti-Rho) antibodies in human normal immunoglobulin for intravenous administration (IGIV). A candidate positive control (IGIV+anti-D) and negative control IGIV were compared to corresponding World Health Organization (WHO) International Reference Reagents using a direct haemagglutination reference method. Sixteen (16) laboratories participated in the collaborative study. Further to completion of the study, the materials assayed in the study were granted the status of Ph. Eur. and US FDA reference preparations for controlling the levels of anti-D in IGIV. PMID- 17270133 TI - Collaborative study for the validation of serological methods for potency testing of diphtheria toxoid vaccine (part 2). AB - The study is a contribution to the EDQM's efforts to meet some of the expectations of the 3 Rs: Replacement, Reduction and Refinement of animal assays as proposed by Russell and Burch in 1959 and adopted by the European Union in 1986, and specifically to validate alternative assays to replace, for batch release purposes, the European Pharmacopoeia (Ph. Eur.) in vivo direct challenge procedures for the potency determination of diphtheria toxoid vaccines. The study results may be used in support of the replacement of the multi-dilution direct challenge procedures in different animal models by a single dilution serology test, where appropriate, and to use sera from the same animals for potency testing of several components in combined vaccines. With regard to the latter, the present study explores the possibility of testing both diphtheria and tetanus toxoid potencies using serum from the same animals. PMID- 17270134 TI - Where did that car come from?: Crossing the road when the traffic comes from an unfamiliar direction. AB - Using a virtual road crossing environment, the reported research investigated the road crossing behavior of 12 male pedestrians in familiar and unfamiliar environments. Environment familiarity was manipulated using traffic direction. Seven of the participants were from a country where traffic flows from right to left and five were from countries were traffic flows from left to right. Each participant was asked to cross the road when traffic was coming from both the familiar and the unfamiliar direction for them. Results showed that pedestrians had lower safety ration, or a lower margin of error, in crossing the road when traffic was flowing in an unfamiliar direction, suggesting that pedestrians might be at greater risk of accident in such environments. Implications of these findings are discussed. PMID- 17270135 TI - Do laboratory frontal crash test programs predict driver fatality risk? Evidence from within vehicle line variation in test ratings. AB - A number of studies have examined whether the National Highway Traffic Safety Administration's (NHTSA) frontal crash test results reliably indicate the risk of fatality or injury in serious crashes. The conclusions of these studies are mixed. Generally, studies that examine crashes in the circumstances as close as possible to those of the laboratory test find that crash test results do predict real-world risk, but studies of crashes outside those specific circumstances find either no support for the predictive validity of crash test results or limited support with important inconsistencies. We provide a new test of the predictive validity of the crash test results using information from multiple crash tests within vehicle lines, thus controlling for systematic differences in driver behavior across vehicle lines. Among drivers of passenger cars, we find large, statistically significant differences in fatality risk for vehicles with one- to four-star NHTSA ratings versus a five-star rating. We also examine the Insurance Institute for Highway Safety's frontal offset crash test, though our sample of vehicle lines tested twice or more is considerably smaller than for NHTSA ratings. Our results also support the predictive validity of the frontal offset crash test results for passenger cars, but not for trucks. PMID- 17270136 TI - Field use patterns and performance of child restraints secured by lower anchors and tethers for children (LATCH). AB - A revised attachment system for child restraint systems (CRS), Lower Anchors and Tethers for Children (LATCH), was introduced to address issues of misuse of attachment of the CRS to the vehicle. This study provides the first real-world experience of this new restraint system. Relevant cases were selected from the partners for child passenger safety (PCPS) child-specific crash surveillance system based in the United States. Vehicles qualifying for the PCPS study were those model year 1990 or newer involved in a crash with at least one passenger 200 ng/ml. Among cases of thyroid carcinoma with lymph node metastasis, Lens culinaris Agglutinin reactive thyroglobulin ratios were significantly lower than in patient with thyroid carcinoma without metastasis and those with benign tumor regardless of serum thyroglobulin concentration. CONCLUSION: Measurement of Lens culinaris Agglutinin reactive thyroglobulin ratio in serum may be useful for distinguishing between thyroid carcinoma and benign thyroid tumor. PMID- 17270169 TI - Executive summary. The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guideline: evidence-based practice for point-of-care testing. AB - BACKGROUND: Point-of-care testing (POCT) is clinical laboratory testing conducted close to the site of patient care. POCT has the potential to provide faster test results and therapeutic intervention with improved patient outcomes. However, when over-utilized or used inappropriately POCT results can be misleading and increase healthcare costs. METHODS: The National Academy of Clinical Biochemistry developed evidence-based Laboratory Medicine Practice Guidelines for POCT. RESULTS: These Laboratory Medicine Practice Guidelines systematically review the scientific literature relating POCT to clinical outcomes and offer recommendations to improve the clinical utility of POCT. CONCLUSIONS: These guidelines will be useful to clinicians considering the addition of POCT, to those that question current practices in POCT, and to clinicians seeking evidence based support for POCT in clinical management. These guidelines represent the most comprehensive systematic review of the POCT literature to date and will help define future research that is needed to add to our current POCT knowledge base. PMID- 17270170 TI - Prevention of aortic calcification by etidronate in the renal failure rat model. AB - Our recent clinical study indicated that etidronate may inhibit the progression of aortic calcification in hemodialysis patients. To determine whether etidronate inhibits aortic calcification in renal failure rats, renal failure was induced by subtotal nephrectomy, in which 5/6 of the kidneys were removed. Significant increases in serum creatinine levels were observed 2 weeks after the operation, at which point treatment with etidronate and calcitriol was initiated. Etidronate at 5 or 10 mg/kg significantly reduced the thoracic and abdominal aortic calcification induced by calcitriol. It also reduced the dysfunction in aortic contraction. The elevation of bone metabolism and reduction of bone mineral density observed in the nephrectomized rats were not affected by treatment with 5 mg/kg etidronate. No changes in serum Ca and the product of Ca and P levels were observed between the non etidronate-treated group and the 5 mg/kg etidronate treated group. Moreover, the reduction in the aortic expression of matrix Gla protein mRNA observed in nephrectomized rats was reversed by 5 mg/kg etidronate. These results show that etidronate at concentrations that do not affect the bone mineral density inhibits aortic calcification and recovers vascular dysfunction in renal failure rats. PMID- 17270171 TI - Effect of N-acetylcysteine on plasma adiponectin and renal adiponectin receptors in streptozotocin-induced diabetic rats. AB - This study investigated the effect of N-acetylcysteine on plasma adiponectin, renal adiponectin receptors, lipid metabolism and oxidative stress in streptozotocin-induced diabetic rats. Metabolic parameters, plasma adiponectin level, renal protein expression of adiponectin receptors were analyzed in controls and diabetic rats treated with or without N-acetylcysteine in drinking water for 8 weeks. Plasma lipid, creatinine and free 5-F(2t)-isoprostane levels, urine protein excretion rate, mesangial matrix expansion index, and protein expression of renal connective tissue growth factor (CTGF) were increased in diabetic rats. The decreased plasma adiponectin levels and renal protein expression of adiponectin receptor 1 were accompanied by the decreased renal phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) alpha (Thr172) and protein expression of phospho-acetyl coenzyme A carboxylase (ACC) (Ser79) which led to the increased renal triglyceride levels in diabetic rats. There was no difference in the protein expression of renal adiponectin receptor 2 between control and diabetic rats. N-acetylcysteine treatment attenuated the increased oxidative stress, plasma and renal lipids, urine protein excretion rate, mesangial matrix expansion index, and protein expression of renal CTGF, but did not affect plasma adiponectin levels, renal protein expression of adiponectin receptor 1, phosphorylation of AMPK-alpha (Thr172) and renal protein expression of phospho-ACC (Ser79) in diabetic rats. These results suggested that the decreased plasma adiponectin and renal adiponectin receptor 1 result in the increased renal triglyceride that stimulates renal CTGF expression leading to the renal hypertrophy and the deteriorated renal function in the diabetic rats. N acetylcysteine treatment attenuates the increased oxidative stress, but has no effect on the decreased plasma adiponectin and renal adiponectin receptor 1 in diabetic rats, indicating that oxidative stress may not contribute to the decreased plasma adiponectin and renal adiponectin receptor 1 protein expression in diabetic rats. PMID- 17270172 TI - Pancreatic small cells: analysis of quiescence, long-term maintenance and insulin expression in vitro. AB - We have previously identified a novel population of small cells in human and canine pancreas characterized by immature morphology, quiescence, and a glucose responsive insulin secretion. Based on their immature phenotype and predominant presence in small islets, we have hypothesized that small cells serve as islet progenitors. This hypothesis remains untested, however, due to persistent quiescence and scarcity of small cells in vitro. We have recently developed a culture medium that allowed for modest small cell proliferation. In this study we characterized the expression of genes potentially involved in small cell growth regulation by Q-RT-PCR. Our results suggest that quiescence of small cells correlates with up-regulation of Cdk inhibitors p27(Kip1), p16(INK4a) and p21(CIP1), PTEN, Hep27 and Foxo1a and with down-regulation of c-Myc and the receptors for EGF, FGF2 and HGF. The exit from quiescence correlates with activation of EGFR expression and down-regulation of p27(Kip1) and p16(INK4a). We also report here that small cells can be maintained in long-term non-adherent cultures preserving insulin and glucagon production for up to 208 days. Therefore, expansion of small cells in vitro may have a significant potential for the treatment of diabetes. This study is an important step in understanding the mechanisms involved in small cell growth regulation, which is required to fully evaluate their functional potential. PMID- 17270173 TI - Histochemical and immunohistochemical study on muscle fibers in human extraocular muscle spindles. AB - Human extraocular muscles are unique in several ways including their endowment with proprioceptive organs. Aim of this study was to establish a classification of intrafusal muscle fibers of human extraocular muscles based on their histochemical and immunohistochemical properties and to determine their relationship to extrafusal extraocular muscle fiber types in this respect. Using light microscopy, intrafusal muscle fibers were followed on consecutive cross sections and classified according to the localization of their myonuclei and to their enzyme- and myosin-immunohistochemical characteristics. Sixteen muscle spindles in human extraocular muscles counted as 'true' spindles revealed 27% nuclear chain fibers [40.1 microm+/-10.4; perimeter+/-SD] and 73% anomalous fibers [44.1 microm+/-12]. Seven 'false' muscle spindles showed only anomalous fibers [43.8 microm+/-11.1] and entirely lacked nuclear chain fibers. Six fiber types were distinguished according to their histochemical and myosin heavy chain immunohistochemical properties. Fiber type 1 [46.3 microm+/-13.3] was made up of fast-twitch myosin heavy chain isoform. Fiber type 2 [39.5 microm+/-10] additionally expressed a developmental myosin heavy chain isoform. Fiber type 3 [42.8 microm+/-10.4] consisted of pure slow-twitch positive muscle fibers. Slow twitch MHC and fast-twitch myosin heavy chain isoform were found in fiber type 4 [43.3 microm+/-9]. Fiber types 5 and 6 showed different myosin heavy chain patterns than fiber types 1-4. The vast majority of nuclear chain fibers displayed fiber type 2 features, but 12% of nuclear chain fibers were found to be of fiber type 1. Among anomalous fibers in true spindles the frequency of fiber type 1 was much higher than in false spindles. On the other hand, fiber type 4 was found more often in false than in true spindles. With regard to their histochemical and immunohistochemical properties intrafusal muscle fibers in human extraocular muscles differ both from intrafusal muscle fibers in other skeletal muscles and from extrafusal muscle fibers in extraocular eye muscles. These conspicuous differences to skeletal muscle spindles relate to their morphology and myosin heavy chain characteristics. In particular, the occurrence of anomalous fibers might reflect dynamic neuronal processes and might be necessary for modulating and adapting processes in advancing age, as well as maintaining proprioceptive input during the whole life. PMID- 17270174 TI - Neurotrophic activity of proNGF in vivo. AB - Ectopic expression of nerve growth factor (NGF) in transgenic mice results in the directional growth of sympathetic and/or sensory fibers. For instance, mice that over-express NGF under the control of the glial fibrillary acidic protein (GFAP) promoter exhibit robust axonal sprouting into the cerebellum, with no apparent loss of neurons in peripheral ganglia. Given the disagreement in the literature over whether pro-NGF exerts neurotrophic or apoptotic effects, we assessed the relative levels of proNGF and mature NGF in the cerebella of these transgenic mice. Blinded western blot analyses revealed that proNGF was the major species in both transgenic and wild type mice, with very low levels of mature NGF expression. While transgenic mice displayed significantly higher levels of cerebellar proNGF protein as compared to wild type mice, both strains possessed comparable levels of mature NGF. These data reveal that the ectopic expression of NGF in the cerebellum results in an increase in proNGF rather than mature NGF levels. Together with the robust axonal growth and lack of neuronal death in the ganglia in these animals, our results are clearly consistent with proNGF exhibiting neurotrophic activity in vivo. PMID- 17270175 TI - Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures. AB - The major finding of the present study concerns the marked decrease of respiratory chain complex I activity in the cerebral cortex of immature rats following seizures induced by bilateral intracerebroventricular infusion of dl homocysteic acid (600 nmol/side). This decrease was already evident during the acute phase of seizures (60-90 min after infusion) and persisted for at least 20 h after the seizures. It was selective for complex I since activities of complex II and IV and citrate synthase remained unaffected. Inhibition of complex I activity was not associated with changes in complex I content. Based on enhanced lipoperoxidation and decreased aconitase activity, it can be postulated that oxidative modification is most likely responsible for the observed inhibition. Mitochondrial respiration, as well as cortical ATP levels remained in the control range, apparently due to excess capacity of the complex I documented by energy thresholds. On the other hand, the enhanced production of reactive oxygen species by inhibited complex I was observed in mitochondria from HCA-treated animals. The decrease of complex I activity was substantially attenuated when animals were treated with substances providing an anticonvulsant effect and also with selected free radical scavengers. We can assume that inhibition of complex I may elicit enhanced formation of reactive oxygen species and contribute thus to neuronal injury demonstrated in this model. PMID- 17270177 TI - Trypanosoma cruzi: exploring the nuclear genome of zymodeme 3 stocks by chromosome size polymorphism. AB - Chagas disease is emerging in the Brazilian Amazon. We evaluated the position of eight zymodeme 3 isolates from Amazonian sylvatic vectors and one human case in relation to Trypanosoma cruzi I and II major groups and hybrid strains by chromosome size polymorphism. Nineteen isolates were analyzed by mapping nine coding sequences on chromosomal bands (0.6-3.3Mbp). Numerical analysis was based on the absolute chromosomal size difference index (aCSDI). A dendrogram was obtained applying the minimum evolution criterion and considering the aCSDI values to estimate the branch lengths. The isolates were distributed in four groups. Group A clustered hybrid isolates; Groups B and C, T. cruzi II and T. cruzi I isolates, respectively. Seven Z3 stocks were clustered in Group D, which showed low intra-group diversity and was the most divergent. The proportion of two different-sized homologous chromosomes was determined. Wild vectors harboring Z3 stocks constitute a potential reservoir of human infection in the Amazon. PMID- 17270176 TI - Impaired expression of postsynaptic density proteins in the hippocampal CA1 region of rats following perinatal hypoxia. AB - Perinatal hypoxia is an important cause of brain injury amongst the newborn, such injury often resulting in an increased risk of impaired performance as regards learning and memory in later life for the affected individual. The postsynaptic density 95 (PSD-95) protein is a cytoskeletal specialization involved in the anchoring of N-methyl-d-aspartate (NMDA) receptors in postsynaptic neurons and has been reported to serve several important functions (e.g., synaptogenesis, synaptic plasticity and learning and memory performance) for the mammalian brain. Herein we investigated the long-term effects of perinatal hypoxia upon the complex of PSD-95 with NMDAR subunits by means of downstream signalling cAMP response element binding protein (CREB) phosphorylation at the Serine-133 locus (CREB(Ser-133) phosphorylation) within the hippocampal CA1 area (an essential integration area for mammalian learning and memory) within test-rat brains, as well as the effects upon afflicted-individual long-term learning and memory performance. We also assessed the therapeutic efficacy of dopamine D1/D5 receptor (D1/D5R) activation for such study animals. Perinatal hypoxia on postnatal day ten (P10) led to impaired performance as regards long-term spatial learning and memory (as determined on P45) associated with decreases in the level of CREB(Ser 133) phosphorylation and decreases in the expression of the complex of PSD-95 with NMDAR subunits (NR1, NR2A, and NR2B). In addition, activation of the D1/D5R via A68930 (a selective, CNS-permeable agonist of D1/D5Rs) administration (2 mg/kg/day, P17-23 inclusively) markedly attenuated the hypoxia-induced deleterious effects, suggesting an effective therapeutic efficacy for A68930. Our results demonstrate the long-term effects of perinatal hypoxia upon the developing brain and provide additional insights into the relative vulnerability of postsynaptic density (PSD) proteins to such insult, as well as the impairment of downstream transcription signalling CREB(Ser-133) phosphorylation following perinatal hypoxia. More importantly, D1/D5R activation following perinatal hypoxia may be an alternative therapeutic strategy to that which is currently available and may offer significant clinical potential for hypoxia sufferers. PMID- 17270178 TI - RNA interference-mediated silencing of the bursicon gene induces defects in wing expansion of silkworm. AB - We studied the role of the bursicon gene in wing expansion. First, we investigated its expression at different developmental stages in the silkworm, Bombyx mori. Bursicon gene was expressed at low levels in larvae, high levels in pupae, and low levels again in adults. Then, we injected the double-stranded bursicon RNA into B. mori pupae to test RNA interference. The level of bursicon mRNA was reduced significantly in pupae, and a deficit in wing expansion was observed in adults. In addition, the differential display reverse transcription polymerase chain reaction (DD-RT-PCR) was used to reveal differences in the expression of transcripts in response to the inhibition of bursicon. In conclusion, bursicon plays a key role in the stereotyped behavioral program involved in wing expansion. PMID- 17270179 TI - Three-dimensional cell organization leads to almost immediate HRE activity as demonstrated by molecular imaging of MG-63 spheroids using two-photon excitation microscopy. AB - Hypoxia through HRE (hypoxia-responsive element) activity in MG-63 human osteosarcoma cells grown in monolayer and as very small, three-dimensional tumor spheroids was investigated using molecular imaging techniques. MG-63 cells were stably transfected with a vector constructed with multiple copies of the HRE sequence of the human vascular endothelial growth factor (VEGF) gene and with the enhanced green fluorescent protein (EGFP) coding sequence. During hypoxia when HIF-1alpha (hypoxia-inducible factor-1alpha) is stabilized, the binding of HIF-1 to the HRE sequences of the vector allows the transcription of EGFP and the appearance of fluorescence. Transfected monolayer cells were characterized by flow cytometric analysis in response to various hypoxic conditions and HIF-1alpha expression in these cells was assessed by Western blotting. Two-photon excitation (TPE) microscopy was then used to examine both MG-63-transfected monolayer cells and spheroids at 2 and 5 days of growth in normoxic conditions. Monolayer cells reveal almost no fluorescence, whereas even very small spheroids (<100 microm) after 2 days of growth contain regions of high fluorescence. For the first time in the literature, at least to our knowledge, it is demonstrated, using highly sensitive and non-perturbing molecular imaging techniques, that three-dimensional cell organization leads to almost immediate HRE activation. This activation of the HRE sequences, which control a wide variety of genes, suggests that monolayer cells and spheroids of the MG-63 cell line have different genes activated and thus diverse functional activities. PMID- 17270181 TI - A comparison of the outcomes between twin and reduced twin pregnancies produced through assisted reproduction. AB - OBJECTIVE: To compare the outcome of twin pregnancies, derived from IVF cycles, with and without fetal reduction. DESIGN: A retrospective cohort study. SETTING: The IVF Division of the Lee Women's Hospital, Taiwan. PATIENT(S): Seven hundred forty-two twin pregnancies, including 389 nonreduced pregnancies, 353 of which resulted from fetal reduction. INTERVENTION(S): Selective fetal reduction for high-order multiple pregnancies. MAIN OUTCOME MEASURE(S): The rates of extreme prematurity and prematurity (i.e., less than 28 and 36 weeks gestational age, respectively), frequency of birth weight discordance, mean birth weight of twins, neonatal mortality, and morbidity. RESULT(S): The fetal reduction group was associated with a higher incidence of extreme prematurity, prematurity, and lower birth weight than the nonreduced group, although the impact was relatively small. These findings were more pronounced among patients with a higher initial number of fetuses. The rates of discordant birth weights between the two groups were not significantly different. CONCLUSION(S): High-order multiple pregnancies after fetal reduction is still associated with a mild increased risk of premature delivery and low birth weight when compared to nonreduced twin pregnancies. These results provide an additional reason to limit the number of embryos transferred during IVF. PMID- 17270180 TI - Influence of hysterectomy on long-term fracture risk. AB - OBJECTIVE: To assess long-term fracture risk after hysterectomy, with or without oophorectomy. DESIGN: Population-based, cohort study. SETTING: Olmsted County, Minnesota. PATIENT(S): Women residing in Olmsted County (n = 9,258) who underwent hysterectomy in 1965-2002, compared to an equal number of age- and sex-matched community controls. INTERVENTION(S): Observational study of the effect of hysterectomy for various indications on subsequent fractures. MAIN OUTCOME MEASURE(S): Fractures of any type, and at osteoporotic sites (e.g., hip, spine, or wrist) alone, as assessed by electronic review of inpatient and outpatient diagnoses in the community. RESULT(S): Compared with controls, there was a significant increase (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.13 1.29) in overall fracture risk among the women with a hysterectomy, but osteoporotic fracture risk was not elevated (HR, 1.09; 95% CI, 0.98-1.22). Most hysterectomy indications were associated with fractures generally, although these were not often statistically significant. Only operations for a uterine prolapse were associated with osteoporotic fractures (HR, 1.33; 95% CI, 1.01-1.74). Oophorectomy was not an independent predictor of fracture risk (HR, 1.0; 95% CI, 0.98-1.15). CONCLUSION(S): Hysterectomy does not appear to pose much long-term risk for fractures, but the association of fractures with surgery for uterine prolapse deserves further attention. PMID- 17270182 TI - Midluteal phase Doppler assessment of uterine artery blood flow in nonpregnant women having a history of recurrent spontaneous abortions: correlation to different etiologies. AB - OBJECTIVE: To compare the impedance to uterine artery blood flow, during the midluteal phase, in women with recurrent spontaneous abortion (RSA) as compared to normal fertile controls. DESIGN: A prospective study involving women with a history of RSA and fertile controls. SETTING: University of Rome "Tor Vergata." PATIENT(S): Two hundred thirty women with RSA and 50 fertile controls referred for routine examination. INTERVENTION(S): Transvaginal Doppler examination of uterine arteries during the midluteal phase of untreated cycles. MAIN OUTCOME MEASURE(S): The mean pulsatility index (PI) of uterine arteries. RESULT(S): Uterine arteries PI values in RSA patients (2.42 +/- 0.79) were significantly higher with respect to those found in the control group (2.08 +/- 0.47). When patients were grouped according to the different RSA causes, the highest PI values were found among patients with uterine abnormalities (2.82 +/- 1.0), antiphospholipid antibodies syndrome (2.70 +/- 1.1), and unexplained RSA (2.60 +/ 0.7). These values were significantly higher with respect to that found in the control group. No differences were observed in PI values between fertile patients and those with RSA due to thyroid abnormalities (2.10 +/- 0.55), inherited thrombophilia (2.03 +/- 0.45), autoimmune pathology (2.34 +/- 1.18), and genetic anomalies (2.47 +/- 0.54). Similar results were observed when patients were grouped according to primary and secondary RSA. CONCLUSION(S): Increased resistance to uterine blood flow may be an important contributing factor to some causes of RSA and may represent an independent indication of the risk of pregnancy loss. PMID- 17270183 TI - Preliminary evidence of glycogen synthase kinase 3 beta as a genetic determinant of polycystic ovary syndrome. AB - In this study of 352 women with polycystic ovary syndrome (PCOS) and 289 control women, haplotypes spanning the gene for glycogen synthase kinase 3beta (GSK3B) were constructed on the basis of nine single-nucleotide polymorphisms in white and black subjects separately. In each racial group, we observed that a specific, although different, GSK3B haplotype was associated with increased frequency of PCOS, suggesting that GSK3beta contributes to the pathophysiology and inherited basis of PCOS. PMID- 17270184 TI - Protective effects of pituitary adenylate cyclase activating polypeptide in endothelial cells against oxidative stress-induced apoptosis. AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide that has various different functions in the nervous system and in non-neural tissues. Little is known about the effects of PACAP in endothelial cells. The aim of the present study was to investigate the effects of PACAP on endothelial cell survival and apoptotic signaling pathways under oxidative stress. Mouse hemangioendothelioma (EOMA) cells were exposed to 0.5mM H(2)O(2) which resulted in a marked reduction of cell viability and a parallel increase of apoptotic cells assessed by MTT test and flow cytometry. Co incubation with 20nM PACAP1-38 increased cell viability and reduced the percentage of apoptotic cells. Flow cytometry analysis showed that oxidative stress reduced the phosphorylation of the anti-apoptotic ERK and increased the phosphorylation of the pro-apoptotic JNK and p38 MAP kinases. PACAP1-38 treatment ameliorated these changes: levels of phospho-ERK were elevated and those of phospho-JNK and p38 were decreased. All these effects were abolished by simultaneous treatment with the PACAP antagonist PACAP6-38. In summary, our results show that PACAP effectively protects endothelial cells against the apoptosis-inducing effects of oxidative stress. PMID- 17270185 TI - Dose-response relationship of 15alpha-hydroxylated sex steroids to gonadotropin releasing hormones and pituitary extract in male sea lampreys (Petromyzon marinus). AB - The sea lamprey (Petromyzon marinus) is one of the earliest extant vertebrates for which the hypothalamic-pituitary-gonadal (HPG) axis has been shown to control and regulate reproduction in a similar fashion to gnathostome vertebrates. While the two forms of gonadotropin-releasing hormones in the sea lamprey (GnRH I and GnRH III) have been studied extensively, their in vivo effect on synthesis of 15alpha-hydroxytestosterone (15alpha-T) and 15alpha-hydroxyprogesterone (15alpha P) have only been partially characterized. In the present study, plasma concentrations of 15alpha-T and 15alpha-P were measured in prespermiating sea lampreys that were given a single injection of either GnRH I or GnRH III in doses ranging from 5 to 100 microg/kg, or of pituitary extract (as a source of gonadotropin). Plasma was sampled at 1-6h and 6-48 h post-injection, in separate experiments, in order to characterize the peak and duration of responses. 15alpha T plasma concentrations increased slightly in response to all three treatments, but not in a dose-dependent manner, and the timing of peak concentrations varied between doses. However, 15alpha-P plasma concentrations showed a greater range of response (between 1 and 100 ng/ml) and were clearly correlated with the injection dose. Plasma concentrations of 15alpha-P also responded to far lower doses of GnRH I and GnRH III than any other steroid previously investigated in lampreys. The plasma concentrations of 15alpha-P peaked at 6h after injection for all three treatments, and levels reached a mean of 53.1 ng/ml. In female lampreys that were injected twice with 50 microg/ml GnRH I or III, 15alpha-T concentrations did not exceed 0.5 ng/ml and 15alpha-P concentrations did not exceed 1 ng/ml. These results lend further support to the hypothesis that 15alpha-P plays an important role in the reproductive endocrinology of male lampreys. PMID- 17270186 TI - Arginine vasotocin promotes urea permeability through urea transporter expressed in the toad urinary bladder cells. AB - We previously isolated a cDNA of a urea transporter (Bufo UT) from the kidney of the marine toad, Bufo marinus, and demonstrated that the Bufo UT was specifically localized on the epithelial membrane of the early distal tubules in the kidney and urinary bladder. In the present study, the function of Bufo UT was investigated using a Xenopus oocytes expression system. Further, we examined the effects of arginine vasotocin (AVT) on urea transport in isolated cells from the toad urinary bladder. When expressed in Xenopus oocytes Bufo UT induced more than a 10-fold increase in [(14)C]urea uptake compared with water-injected control oocytes. Phloretin, a urea transport inhibitor, fully blocked the increase of urea uptake. In epithelial cells isolated from the toad urinary bladder, addition of AVT to the medium increased the urea uptake in a concentration-dependent manner (10(-12)-10(-8)M). To examine the relationship between the Bufo UT protein expression and an increase of urea transportability, we analyzed the time course of the Bufo UT expression levels and urea uptake in the cells treated with 10( 8)M AVT. Treatment of 10(-8)M AVT increased the urea uptake in the cells after 24 and 48h incubation, but not after 12h. According to the immunoblot analysis, UT protein expression was coincident with the results of urea uptake in the AVT treated cells. These results suggest that Bufo UT isolated from the kidney, functions as an AVT-mediated urea transporter in the urinary bladder of the toad. PMID- 17270187 TI - Interfragmentary compression forces of scaphoid screws in a sawbone cylinder model. AB - Various screws have been developed to stabilise fractures of the scaphoid. Commonly used are the Herbert, the HBS, the 3-mm AO and the Acutrak screws. Not long ago a new screw, the Twin Fix, was introduced. This is cannulated and similar in shape and appearance to the classical Herbert screw. In our test series we compared the maximum achievable compression forces of the Twin Fix screw with that of three other screws (AO, HBS and Acutrak screws). To avoid the variations of density, stiffness and rigidity in natural bone, a polyurethane sawbone-based test setup was used. The test series included 10 screws of each type. The compression force was measured using a special strain gauge. The mean compression force was significantly higher for the Twin Fix screw (8+/-1N) and the Acutrak screw (7.6+/-0.4/0.6N) in relation to the AO screw (6.8+/-1.0/1.4N) and HBS screw (2+/-1N). We found the Twin Fix and Acutrak screws to be promising in the treatment of scaphoid fractures. PMID- 17270189 TI - Tuberculous endometritis presenting as postmenopausal bleeding. PMID- 17270188 TI - Cesarean vs. vaginal birth for term breech presentation in 2 different study periods. AB - OBJECTIVE: To compare outcomes for fetuses at term in breech presentation during 2 periods when different delivery policies were in effect. METHODS: Outcomes of the 392 planned vaginal deliveries and 1160 elective cesarean sections (CSs) performed from January 1, 1988, through December 31, 2000, were compared with those of the 24 emergency vaginal deliveries, the 403 planned CSs, and 75 emergency CSs performed from January 1, 2001 through December 31, 2004 at Alexandra Hospital, Athens, Greece. RESULTS: A significant difference was found in rates of low 5-minute Apgar score, birth trauma, serious neonatal morbidity, and admission to the neonatal intensive care unit (0% vs. 1.02% [P=0.004], 1.02% vs. 0% [P=0.004], 3.06% vs. 0.43% [P<0.001], and 2.8% vs. 0.43% [P<0.001], respectively) between neonates born by planned vaginal delivery and those born by elective CS during the first period. Only a reduction in rates of admission to the neonatal intermediate care unit was found between the first and second periods. CONCLUSIONS: Planned CS was found to be safer than planned vaginal delivery for fetuses at term in breech presentation. However, the study did not demonstrate that the change in policy improved neonatal outcome. PMID- 17270190 TI - Outcomes of acutely ill older hospitalized patients following implementation of tailored models of care: a repeated measures (pre- and post-intervention) design. AB - BACKGROUND: There is a lack of research investigating models of nursing care for older hospitalised patients that address the nursing needs of this group. OBJECTIVES: The objective of this study is to evaluate the efficacy of models of care for acutely older patients tailored to two contexts: an aged care specific ward and a medical ward. DESIGN: This is a repeated measures design. Efficacy of the models was evaluated in terms of: patient and nurses' satisfaction with care provided; increased activities of daily living; reduced unplanned hospital readmissions; and medication knowledge. SETTINGS: An aged care specific ward and a medical ward in two Sydney teaching hospitals. PARTICIPANTS: There were two groups of patients aged 65 years or older who were admitted to hospital for an acute illness: those admitted prior to model implementation (n=232) and those admitted during model implementation (n=116). Patients with moderate or severe dementia were excluded. The two groups of nurses were the pre-model group (n=90) who were working on the medical and aged care wards for the study prior to model implementation, and the post-model group (n=22), who were the nurses working on the wards during model implementation. METHODS: Action research was used to develop the models of care in two wards: one for an aged care specific ward and another for a general medical ward where older patients were admitted. The models developed were based on empirical data gathered in an earlier phase of this study. RESULTS: The models were successful in both wards in terms of increasing satisfaction levels in patients and nurses (p<0.001), increasing functional independence as measured by activities of daily living (p<0.01), and increasing medication knowledge (p<0.001). CONCLUSIONS: Findings indicate that models of care developed by nurses using an evidence-based action research strategy can enhance both satisfaction and health outcomes in older patients. PMID- 17270191 TI - Kinematic analysis of the 100-m wheelchair race. AB - The purpose of this study was to compare the speed and selected stroke cycle characteristics during different phases of the 100-m wheelchair race for paraplegic athletes. Four male and two female wheelchair racers in T4 classification and one male and three female athletes in T3 classification served as the participants. Two S-VHS camcorders (60 fields/s) were panned horizontally to cover the first and second 50 m of the 100-m race, respectively. Average speed, stroke length and frequency, contact and recovery times during the first 10 m (initial acceleration phase, IAP), the maximum speed phase (MSP), and the last 10 m (final phase, FP) of the race were determined. For each parameter, an ANOVA with repeated measures was performed and Tukey post hoc tests were completed when appropriate (alpha=0.01). The 100-m times ranged from 16.10 to 22.18 s. Significant differences were found between IAP and MSP and between IAP and FP in stroke speed, stroke length, and push and recovery times, but not in stroke frequency. The relatively constant stroke frequency across different phases may suggest that wheelchair racers like to maintain the same stroking rhythm throughout a 100-m race. The distance and time needed to reach the maximum speed ranged from 43.9 m and 11.2 s to 82.2 m and 18.9 s, respectively. The significant correlation between 100-m time and maximum speed (p<0.001) signifies the importance of maximum speed in determining 100-m performance. PMID- 17270192 TI - Computational hip joint simulator for wear and heat generation. AB - This paper presents a computational simulator for the hip to compute the wear and heat generation on artificial joints. The friction produced on artificial hip joints originates wear rates that can lead to failure of the implant. Furthermore, the frictional heating can increase the wear. The developed computational model calculates the wear in the joint and the temperature in the surrounding zone, allowing the use of different combinations of joint materials, daily activities and different individuals. The pressure distribution on the joint bearing surfaces is obtained with the solution of a contact model. The heat generation by friction and the volumetric wear is computed from the pressure distribution and the sliding distance. The temperature is obtained from the solution of a transient heat conduction problem that includes the time-dependent heat generated by friction. The contact and heat conduction problems are solved numerically with the Finite Element Method. The developed computational model performs a full simulation of the acetabular bearing surface behaviour, which is useful for acetabular cup design and material selection. The results obtained by the present model agree with experimental and clinical data, as well as other numerical studies. PMID- 17270193 TI - Accuracy of circular contact area measurements with thin-film pressure sensors. AB - Contact area is often used to characterize the biomechanical properties of joints, especially in testing of injury and joint replacement. Several methods have been developed to measure contact area, including piezo-resistive thin-film arrays. The purpose of this study was to determine the accuracy with which one of these systems (Tekscan, Inc., South Boston, MA) could measure the contact area of flat-ended circular indenters of varying known sizes. Static loads ranging from 1000 to 7000 N were applied to four flat, circular indenters (1140, 2027, 3167, and 4560 mm(2)) and the contact areas were recorded with Tekscan 5076 sensor. Similar testing was carried out on a 4000 sensor. I-scan software (Tekscan Inc., South Boston, MA) was used to analyze the Tekscan-recorded area measurements. The Tekscan data were also post-processed to filter out sensel signal intensity values that were at least two standard deviations from the average sensel signal intensity values of the sensor matrix. Unprocessed Tekscan measurements with the 5076 sensor had area percent errors ranging from 5% to 27%. The filtering algorithm reduced most errors to less than 1%. Similar trends of improved accuracy with post-filtering were found with the 4000 sensor. While this method of thresholding out the sensels with the lowest signal intensity values may not work for all surfaces and indenter shapes, it provides a new approach to improve the accuracy of contact area measurements collected with the Tekscan system. PMID- 17270194 TI - Validation of net joint loads calculated by inverse dynamics in case of complex movements: application to balance recovery movements. AB - The joint forces and moments driving the motion of a human subject are classically computed by an inverse dynamic calculation. However, even if this process is theoretically simple, many sources of errors may lead to huge inaccuracies in the results. Moreover, a direct comparison with in vivo measured loads or with "gold standard" values from literature is only possible for very specific studies. Therefore, assessing the inaccuracy of inverse dynamic results is not a trivial problem and a simple method is still required. This paper presents a simple method to evaluate both: (1) the consistency of the results obtained by inverse dynamics; (2) the influence of possible modifications in the inverse dynamic hypotheses. This technique concerns recursive calculation performed on full kinematic chains, and consists in evaluating the loads obtained by two different recursive strategies. It has been applied to complex 3D whole body movements of balance recovery. A recursive Newton-Euler procedure was used to compute the net joint loads. Two models were used to represent the subject bodies, considering or not the upper body as a unique rigid segment. The inertial parameters of the body segments were estimated from two different sets of scaling equations [De Leva, P., 1996. Adjustments to Zatsiorsky-Suleyanov's segment inertia parameters. Journal of Biomechanics 29, 1223-1230; Dumas, R., Cheze, L., Verriest, J.-P., 2006b. Adjustments to McConville et al. and Young et al. Body Segment Inertial Parameters. Journal of Biomechanics, in press]. Using this comparison technique, it has been shown that, for the balance recovery motions investigated: (1) the use of the scaling equations proposed by Dumas et al., instead of those proposed by De Leva, improves the consistency of the results (average relative influence up to 30% for the transversal moment); (2) the arm motions dynamically influence the recovery motion in a non negligible way (average relative influence up to 15% and 30% for the longitudinal force and the transversal moment, respectively). PMID- 17270195 TI - Validation of chromatographic methods: evaluation of detection and quantification limits in the determination of impurities in omeprazole. AB - To guarantee that an analytical procedure gives reliable, exact and interpretable information about a sample, it must be validated. Two ambiguous parameters are detection limit and quantification limit. The determination of these limits is still of great concern and there are still a variety of procedures described in the current literature. The fundamental objective of the present work is to apply the different recommendations suggested by official guidelines for the quantitative determination of omeprazole and its impurities (omeprazole sulphone and 5-hydroxy-omeprazole) in capsules and tablets using high performance liquid chromatography with UV detection. The importance of calibration linearity in the context of the quantification limit is considered, since one of the approaches, the estimated concentrations of this limit, are deduced from the regression line. The values of the detection limit and the quantification limit obtained show that, in chromatographic analyses, the best method is that based on the use of the parameters obtained from the analytical curve, which are statistically reliable. It was shown that smaller values of the detection limit and the quantification limit were obtained by the visual approach and by the method using the signal-to-noise ratio. However, these values may reflect a subjective evaluation, prone to error and large variations. This was confirmed by showing that these methods result in values that fall outside the linear range of the method. PMID- 17270196 TI - Solid-phase extraction and liquid chromatography--mass spectrometry for the determination of free fatty acids in shellfish. AB - A novel analytical protocol for the determination of free fatty acids (FFAs; saturated, monounsaturated and polyunsaturated) in shellfish using electrospray ionisation and liquid chromatography-mass spectrometry (LC-MS) is described. Total lipids were extracted from four commercially important shellfish species using chloroform-methanol in a modification of the traditionally used Bligh and Dyer method. FFAs were recovered from lipidic shellfish extracts by solid-phase extraction (SPE) on an aminopropyl-silica column using a 98:2 v/v diethyl ether (DEE)-acetic acid solution. Ether extracts containing the FFAs were evaporated and reconstituted in 70:30 v/v methanol-chloroform before analysis by LC-MS. The limits of quantification (LOQs) of the method ranged from 60 to 560 microgg(-1) wet weight depending on the different FFAs determined with selected ion monitoring (SIM). Results demonstrate that LC-MS is well suited for identification and quantification of FFAs in shellfish and negates the use of sample derivatisation required in gas chromatographic analysis. PMID- 17270197 TI - Preparative isolation of four ginsenosides from Korean red ginseng (steam-treated Panax ginseng C. A. Meyer), by high-speed counter-current chromatography coupled with evaporative light scattering detection. AB - Ginseng (Panax ginseng C. A. Meyer) has been well known to have a variety of ginsenosides that show diverse biological activities. Especially, the components of ginsenosides are quite different depending on the processing method. Recently, there have been several reports showing that less polar ginsenosides from Korean red ginseng (steam-treated Panax ginseng) have potent biological activities such as radical scavenging, vasodilating and anti-tumor activities. In this study, we have isolated four known ginsenosides Rg3, Rk1, Rg5 and F4 from Korean red ginseng by high-speed counter-current chromatography (HSCCC) coupled with evaporative light scattering detection (ELSD). The enriched saponin fraction (350 mg) was separated by using methylene chloride-methanol-water-isopropanol (6:6:4:1, v/v) as the two-phase solvent system and yielded 28.6 mg of Rg5, 26.6 mg of Rk1, 32.2 mg of Rg3 and 8.1 mg of F4. The purity of these ginsenosides was assessed by HPLC-ELSD to be over 95%, and their structures were characterized by electrospray ionization mass spectrometry (ESI-MS), (1)H NMR and (13)C NMR. PMID- 17270198 TI - Structural control of peptide-coated gold nanoparticle assemblies by the conformational transition of surface peptides. AB - Gold nanoparticles having peptide chains on the surfaces have been prepared yb ring-opening polymerization of gamma-methyl L-glutamate N-carboxyanhydride with fixed amino groups on the nanoparticle surface as an initiator. The number of peptide chains on the surface was adjusted to ca. 2 molecules per gold nanoparticle by controlling the number of fixed amino groups on the surface. The peptide chains on the surface were partially saponified to obtain poly(gamma methyl L-glutamate-co-L-glutamic acid) with 28 mol% of glutamic acid residues. The number-average molecular weight of the peptide was 73,000. We described structural control of the peptide-coated gold nanoparticle assembly by conformational transition of the surface peptides. In deionized water, the peptide chains on the nanoparticle took a random coil conformation, and the individual nanoparticles existed in dispersed globular species. On the other hand, the peptide chains on the nanoparticle took an alpha-helical conformation in trifluoroethanol. Under this condition, the alpha-helical peptide chains on distinct gold nanoparticles connected the nanoparticles to form a fibril assembly owing to the dipole-dipole interaction between the surface peptide chains. The morphology of the peptide-coated gold nanoparticle assembly could be controlled by the conformational transition of surface peptides, which was attended by solution composition changes. PMID- 17270199 TI - Mesoporous silica spheres from colloids. AB - A novel method has been developed to synthesize mesoporous silica spheres using commercial silica colloids (SNOWTEX) as precursors and electrolytes (ammonium nitrate and sodium chloride) as destabilizers. Crosslinked polyacrylamide hydrogel was used as a temporary barrier to obtain dispersible spherical mesoporous silica particles. The influences of synthesis conditions including solution composition and calcination temperature on the formation of the mesoporous silica particles were systematically investigated. The structure and morphology of the mesoporous silica particles were characterized via scanning electron microscopy (SEM) and N2 sorption technique. Mesoporous silica particles with particle diameters ranging from 0.5 to 1.6 microm were produced whilst the BET surface area was in the range of 31-123 m2 g-1. Their pore size could be adjusted from 14.1 to 28.8 nm by increasing the starting particle diameter from 20-30 nm up to 70-100 nm. A simple and cost effective method is reported that should open up new opportunities for the synthesis of scalable host materials with controllable structures. PMID- 17270200 TI - Preparation and characterization of polyaniline/manganese dioxide composites and their catalytic activity. AB - This paper is devoted to the preparation of polyaniline/MnO2 (PANI/MnO2) composites via chemical oxidation of aniline in H2SO4 medium using beta-MnO2 as an oxidant. The parameters affecting the polymerization reaction are considered. These parameters are [aniline], amount of beta-MnO2, stirring time, and polymerization temperature. SEM, FT-IR, XRD, and TGA techniques are used to characterize the resulting composites. XRD measurements reveal the distortion of the crystal structure of beta-MnO2 after the polymerization reaction. Thus, the XRD pattern of PANI is predominating. The crystalline composites are obtained using higher molar ratio of [Ox]/[ANI] and at higher temperature. Increasing the amount of beta-MnO2 led to an increase in the acidic character of the obtained composites due to adsorption of excess H+ on the oxide surface. The thermal stability of the composites decreased with increasing both [aniline] and stirring time, while it increased with increasing amount of beta-MnO2. The applications of the composites in the oxidative degradation of Direct Red 81, Acid Blue 92, and Indigo Carmine dyes exhibited good catalytic activity in the presence of H2O2 as an oxidant. The reactions followed first-order kinetics and the rate constants were determined. The degradation reaction involved the catalytic action of the PANI counterpart of the composite toward H2O2 decomposition, which can lead to the generation of HO radicals as a highly efficient oxidant attacking the target dyes. The detailed kinetic studies and the mechanism of these catalytic reactions are under consideration in our group. PMID- 17270201 TI - Surface characterization and platelet compatibility evaluation of the binary mixed self-assembled monolayers. AB - This report describes a technique that used mixed self-assembled monolayer (SAM) as a model surface to evaluate the effect of steric hindrance on the SAM packing quality and its platelet compatibility. Two series of binary mixed SAMs were formed by mixing the bulky terminated alkanethiol (HS(CH2)10PO3H2) with a smaller terminated one (HS(CH2)9CH3 and HS(CH2)11OH) respectively. Surface characterization results showed the hydrophilicity on these two series of mixed SAMs changed with the solution mole fraction of PO3H2 terminated thiol, chi(PO3H2,soln), and reached to a nearly constant value as chi(PO3H2,soln) was 0.6 for PO3H2+CH3 SAM and 0.4 for PO3H2+OH SAM. This finding should be due to the gradual saturation of surface PO3H2 functionality on these mixed SAMs. The XPS analysis indicated the addition of the CH3 and OH terminated thiol could reduce the steric hindrance effect of PO3H2 functionality on monolayer formation and, henceforth, improve the SAM packing quality. In vitro platelet adhesion assay revealed the platelet compatibility on the PO3H2+OH SAMs was better than that on the PO3H2+CH3 and the pure PO3H2 ones. Moreover, the PO3H2+OH SAM with a low chi(PO3H2,soln) value exhibited the least platelet activating property of these two mixed SAM systems. These findings suggested that material's surface wettability and surface charge density should act collectively in affecting its platelet compatibility. PMID- 17270202 TI - Myelin vacuolation, optic neuropathy and retinal degeneration after closantel overdosage in sheep and in a goat. AB - Toxicity of closantel, a halogenated salicylanilide anthelmintic, is described in 11 sheep and a goat, humanely killed 4-70 days after accidental overdosage. Status spongiosis of the cerebrum and cerebellum was present, its severity decreasing with time after treatment. Ultrastructurally, vacuoles in the cerebral white matter were seen to be intramyelinic due to splitting of myelin lamellae at the intraperiod lines, indicating myelin oedema. In the optic nerves, Wallerian degeneration and eventual fibrosis and atrophy of the nerves followed myelin vacuolation. Lesions in the optic nerves were particularly advanced in the intracanalicular portion, indicating a compressive neuropathy within the optic canal. Acute retinal lesions consisted of papilloedema, necrosis of the outer retinal layers (especially the photoreceptor layer), and retinal separation in tapetal and non-tapetal areas. In more chronic cases, the outer nuclear layer was diffusely attenuated and generally reduced to a single row of cells. PMID- 17270203 TI - Changes in morphology and key cytokine gene expression after intradermal injection of louse (Bovicola ovis) antigen in sheep with naturally occurring atopic dermatitis. AB - Groups of louse-infested and louse-naive lambs (n=6 or 7) were used in two experiments to determine the sequential tissue response (macroscopical, microscopical and key cytokine mRNA) to intradermal injection of crude louse (Bovicola ovis) antigen over a period of 72 or 96 h. Histamine diphosphate and phosphate-buffered saline/glycerol (antigen vehicle control) solutions were also injected intradermally in each lamb for comparison. In both experiments, louse infested lambs showed immediate and late-phase responses (LPRs) to louse antigen that differed significantly from the responses in the louse-naive lambs. In experiment 1, biopsy samples taken at 7, 24, 48 and 96 h after injections showed more extensive dermal inflammation and leucocyte infiltration in response to louse antigen in louse-infested than in louse-naive lambs. Eosinophils were significantly more numerous in the dermis of louse-infested lambs after all treatments and increased substantially in these lambs after antigen injection. Additionally, the louse-infested lambs differed from the naive lambs in showing significantly higher mononuclear leucocyte and basophil infiltration and significantly lower neutrophil infiltration after antigen injection. In experiment 2, biopsy samples taken 4, 24, 48 and 72 h after injections showed trends in eosinophil infiltration of the dermis similar to those observed in experiment 1. Peak IL-4 mRNA expression was detected 4 h after antigen injection in the louse-infested lambs and remained significantly elevated at 24 h as compared with the results in the louse-naive lambs. No significant difference in IFN-gamma mRNA expression between the louse-infested and the louse-naive lambs was observed. These results indicated that louse-infested lambs show a cutaneous LPR analogous to that observed in atopic human beings and dogs. However, some differences were observed, including the longer duration of the LPR, the profuse eosinophil infiltration, and an absence of increased IFN-gamma mRNA expression. PMID- 17270204 TI - Primary and secondary heart tumours in dogs and cats. AB - Primary and secondary neoplasms of the canine and feline heart are uncommon. During a 2-year period, 83 dogs suffering from primary cardiac (n=11), extracardiac benign (n=6) or malignant (n=66) tumours and 30 cats with primary cardiac (n=1) or extracardiac (n=29) malignant tumours were examined. Echocardiography revealed four cases of primary cardiac neoplasms in dogs, but secondary heart tumours were not detected. After necropsy, tissue samples from the heart and tumours were examined histologically and immunohistochemically. In dogs, primary neoplasms included seven haemangiosarcomas, two chemodectomas, one rhabdomyosarcoma, and one neurofibrosarcoma. In 24 of 66 dogs examined, metastases of extracardiac neoplasms were found in the heart (15 carcinomas, six malignant lymphomas, three haemangiosarcomas). In cats, one case of primary haemangiosarcoma of the pericardium and five cases of secondary cardiac tumours (two malignant lymphomas, three carcinomas) occurred. Cardiac neoplasms in cats were not identified clinically but were detected by detailed gross sectioning of the heart (n=2) or histopathological examinations (n=3). This study showed an unexpectedly high number (36%) of dogs with cardiac metastases. PMID- 17270205 TI - Species-specificity of a panel of prion protein antibodies for the immunohistochemical study of animal and human prion diseases. AB - Monoclonal antibodies to the prion protein (PrP) have been of critical importance in the neuropathological characterization of PrP-related disease in men and animals. To determine the influence of species-specific amino-acid substitutions recognized by monoclonal antibodies, and to investigate the immunohistochemical reactivity of the latter, analyses were carried out on brain sections of cattle with bovine spongiform encephalopathy, sheep with scrapie, mice infected with scrapie, and human beings with Creutzfeldt-Jakob disease (CJD) or Gerstmann Straussler-Sheinker disease (GSS). Immunoreactivity varied between the antibodies, probably as the result of differences in the amino-acid sequence of the prion protein in the various species. Some monoclonal antibodies against mouse recombinant PrP gave strong signals with bovine, ovine and human PrP(Sc), in addition to murine PrP(Sc), even though the amino-acid sequences determined by the antibody epitope are not fully identical with the amino-acid sequences proper to the species. On the other hand, in certain regions of the PrP sequence, when the species-specificity of the antibodies is defined by one amino-acid substitution, the antibodies revealed no reactivity with other animal species. In the region corresponding to positions 134-159 of murine PrP, immunohistochemical reactivity or species-specificity recognized by the antibodies may be determined by one amino acid corresponding to position 144 of murine PrP. Not all epitopes recognized by a monoclonal antibody play an important role in antigen-antibody reactions in immunohistochemistry. The presence of the core epitope is therefore vital in understanding antibody binding ability. PMID- 17270206 TI - Clinicopathological relevance of tumour grading in canine osteosarcoma. AB - Tumour grading assesses biological aggressiveness and is of prognostic significance in many malignancies. The clinicopathological features of 140 primary canine osteosarcomas and their metastases were analysed, and the interrelations between them and an established grading system and its constituent parameters (mitotic index, necrosis, pleomorphism) were examined. Of these tumours, 35% were grade III (high-grade), 37% grade II and 28% grade I. Primary tumours that had metastasized were of significantly higher grade than non metastatic osteosarcomas. Osteosarcomas belonging to the osteoblastic minimally productive subtype, but not chondroblastic or telangiectatic subtypes, differed from fibroblastic osteosarcomas in being associated with a significantly higher number of high-grade cases. Dogs younger than 4 years of age had osteosarcomas with higher grade, score and mitotic index than did older animals. Appendicular differed from axial tumours in having a higher mitotic index; distal differed from proximal tumours in being of higher grade; cranial tumours differed from tumours in most other sites in being of lower grade and lower mitotic index. Rib osteosarcomas showed a particularly high degree of necrosis. The mitotic index varied widely between tumour locations. Pleomorphism did not have prognostic merit when examined separately, as most osteosarcomas were highly pleomorphic. PMID- 17270207 TI - A simple method for collecting measured whole blood with quantitative recovery of antibody activities for serological surveys. AB - Compliance and acceptance for the finger-prick method of blood collection is generally better than for venipuncture. A finger-prick method of blood collection with quantitative antibody recovery is even more important for seroepidemiological surveys. Finger-prick blood collected and dried onto filter paper has been used; but, unfortunately, this method has several disadvantages, including loss of antibody activity, possible contact contamination from blood spots on adjacent filter papers, and difficulties in extracting antibodies, justifying the search for other methods of collecting and transporting blood samples. We report on a simple method of collecting a measured amount of finger prick blood onto a sample pad, which is immediately transferred to storage/extraction buffer. The diluted blood sample is never dried, and because of the storage buffer, can be transported and stored without refrigeration. Furthermore, the diluted blood samples can then be tested directly without further preparation. We systematically compared several storage/extraction buffers and commercially available filter papers. We showed that antibody recovery was not significantly affected by the type of filter papers used but was significantly affected by the storage/extraction buffer used. The best such buffer is StabilZyme Select. PMID- 17270208 TI - Comparing injection, feeding and topical application methods for treatment of honeybees with octopamine. AB - Entomologists have used a range of techniques to treat insects with neuroactive compounds, but it is not always clear whether different treatment methods are equally effective in delivering a compound to a target organ. Here, we used five different techniques to treat honeybees with 3H-octopamine (3H-OA), and analysed the distribution of the 3H radiolabelled compound within different tissues and how it changed over time. All treatment methods, including injection of the median ocellus, resulted in 3H-OA detection in all parts of the honeybee. Injection through the median ocellus was the most effective method for delivering 3H-OA to the brain. Topical application of 3H-OA dissolved in dimethylformamide (dMF) to the thorax was as effective as thoracic injections of 3H-OA in delivering 3H-OA to the brain, but topical applications to the abdomen were less so. Most of the 3H-OA applied topically remained associated with the cuticle and the tissues of the body segment to which it had been applied. For all treatment methods, 3H-OA was rapidly lost from the brain and head capsule, and accumulated in the abdomen. Our findings demonstrate the value of thoracic topical treatment with compounds dissolved in dMF as an effective non-invasive method for short term, systemic pharmacological treatments. PMID- 17270209 TI - A dissection of the protein-protein interfaces in icosahedral virus capsids. AB - We selected 49 icosahedral virus capsids whose crystal structures are reported in the Protein Data Bank. They belong to the T=1, T=3, pseudo T=3 and other lattice types. We identified in them 779 unique interfaces between pairs of subunits, all repeated by icosahedral symmetry. We analyzed the geometric and physical chemical properties of these interfaces and compared with interfaces in protein-protein complexes and homodimeric proteins, and with crystal packing contacts. The capsids contain one to 16 subunits implicated in three to 66 unique interfaces. Each subunit loses 40-60% of its accessible surface in contacts with an average of 8.5 neighbors. Many of the interfaces are very large with a buried surface area (BSA) that can exceed 10,000 A(2), yet 39% are small with a BSA<800 A(2) comparable to crystal packing contacts. Pairwise capsid interfaces overlap, so that one-third of the residues are part of more than one interface. Those with a BSA>800 A(2) resemble homodimer interfaces in their chemical composition. Relative to the protein surface, they are non-polar, enriched in aliphatic residues and depleted of charged residues, but not of neutral polar residues. They contain one H-bond per about 200 A(2) BSA. Small capsid interfaces (BSA<800 A(2)) are only slightly more polar. They have a similar amino acid composition, but they bury fewer atoms and contain fewer H-bonds for their size. Geometric parameters that estimate the quality of the atomic packing suggest that the small capsid interfaces are loosely packed like crystal packing contacts, whereas the larger interfaces are close-packed as in protein-protein complexes and homodimers. We discuss implications of these findings on the mechanism of capsid assembly, assuming that the larger interfaces form first to yield stable oligomeric species (capsomeres), and that medium-size interfaces allow the stepwise addition of capsomeres to build larger intermediates. PMID- 17270211 TI - Crystal structure of the carboxyltransferase domain of the oxaloacetate decarboxylase Na+ pump from Vibrio cholerae. AB - Oxaloacetate decarboxylase is a membrane-bound multiprotein complex that couples oxaloacetate decarboxylation to sodium ion transport across the membrane. The initial reaction catalyzed by this enzyme machinery is the carboxyl transfer from oxaloacetate to the prosthetic biotin group. The crystal structure of the carboxyltransferase at 1.7 A resolution shows a dimer of alpha(8)beta(8) barrels with an active site metal ion, identified spectroscopically as Zn(2+), at the bottom of a deep cleft. The enzyme is completely inactivated by specific mutagenesis of Asp17, His207 and His209, which serve as ligands for the Zn(2+) metal ion, or by Lys178 near the active site, suggesting that Zn(2+) as well as Lys178 are essential for the catalysis. In the present structure this lysine residue is hydrogen-bonded to Cys148. A potential role of Lys178 as initial acceptor of the carboxyl group from oxaloacetate is discussed. PMID- 17270210 TI - Molecular and functional dissection of a putative RNA-binding region in yeast mitochondrial leucyl-tRNA synthetase. AB - Aminoacylation and editing by leucyl-tRNA synthetases (LeuRS) require migration of the tRNA acceptor stem end between the canonical aminoacylation core and a separate domain called CP1 that is responsible for amino acid editing. The LeuRS CP1 domain can also support group I intron RNA splicing in the yeast mitochondria, although splicing-sensitive sites have been identified on the main body. The RDW peptide, a highly conserved peptide within an RDW-containing motif, resides near one of the beta-strand linkers that connects the main body to the CP1 domain. We hypothesized that the RDW peptide was important for interactions of one or more of the LeuRS-RNA complexes. An assortment of X-ray crystallography structures suggests that the RDW peptide is dynamic and forms unique sets of interactions with the aminoacylation and editing complexes. Mutational analysis identified specific sites within the RDW peptide that failed to support protein synthesis activity in complementation experiments. In vitro enzymatic investigations of mutations at Trp445, Arg449, and Arg451 in yeast mitochondrial LeuRS suggested that these sites within the RDW peptide are critical to the aminoacylation complex, but impacted amino acid editing activity to a much less extent. We propose that these highly conserved sites primarily influence productive tRNA interactions in the aminoacylation complex. PMID- 17270212 TI - PWWP module of human hepatoma-derived growth factor forms a domain-swapped dimer with much higher affinity for heparin. AB - Hepatoma-derived growth factor (hHDGF)-related proteins (HRPs) comprise a new growth factor family sharing a highly conserved and ordered N-terminal PWWP module (residues 1-100, previously referred to as a HATH domain) and a variable disordered C-terminal domain. We have shown that the PWWP module is responsible for heparin binding and have solved its structure in solution. Here, we show that under physiological conditions, both the PWWP module and hHDGF can form dimers. Surface plasmon resonance (SPR) studies revealed that the PWWP dimer binds to heparin with affinity that is two orders of magnitude higher (K(d)=13 nM) than that of the monomeric PWWP module (K(d)=1.2 microM). The monomer-dimer equilibrium properties and NMR structural data together suggest that the PWWP dimer is formed through a domain-swapping mechanism. The domain-swapped PWWP dimer structures were calculated on the basis of the NMR data. The results show that the two PWWP protomers exchange their N-terminal hairpin to form a domain swapped dimer. The two monomers in a dimer are linked by the long flexible L2 loops, a feature supported by NMR relaxation data for the monomer and dimer. The enhanced heparin-binding affinity of the dimer can be rationalized in the framework of the dimer structure. PMID- 17270213 TI - Modeling the contribution of speeding and impaired driving to insurance claim counts and costs when contributing factors are unknown. AB - PROBLEM: There are no specific indicators for distinguishing insurance claims related to speeding and impaired driving in the information warehouse at the Insurance Corporation of British Columbia. Contributing factors are only recorded for that part of the claim data that is also reported by the police. Most published statistics on crashes that are related to alcohol or speeding are based on police-reported data, but this represents only a fraction of all incidents. METHOD: This paper proposes surrogate models to estimate the counts and the average costs associated with speeding and impaired driving to insurance claims when contributing factors are unknown. Using police-reported data, classification rules and logistic regression models are developed to form such estimates. One approach applies classification rules to categorize insurance claims into those related to speeding, impaired driving, and other factors. The counts and the costs of insurance claims for each of these strata and overall are then estimated. A second method models the probability that an insurance claim is related to speeding or impaired driving using logistic regression and uses this to estimate the overall counts and the average costs of the claims. The two methods are compared and evaluated using simulation studies. RESULTS: The logistic regression model was found to be superior to the classification model for predicting insurance claim counts by category, but less efficient at predicting average claim costs. IMPACT: Having estimates of counts and costs of insurance claims related to impaired driving or speeding for all reported crash events provides a more accurate basis for policy-makers to plan changes and benefits of road safety programs. PMID- 17270214 TI - Loss of claudin-1 expression correlates with malignancy of hepatocellular carcinoma. AB - BACKGROUND: The prognosis for the hepatocellular carcinoma (HCC) patient is affected by invasion and metastases. The attenuated expression of adherens junction protein epithelial-cadherin (E-cad) correlates with a more malignant potential in HCC. However, the potential of the claudin (CL) family of tight junctional proteins for HCC prognosis has remained unrecognized. MATERIALS AND METHODS: We immunohistochemically examined the expression of CL-1 and E-cad in resected specimens from 55 HCC cases. The percentage of CL-1- or E-cad-positive cells was counted in HCC cells and the surrounding hepatocytes and scored as 0 (0%), 1 (1-33%), 2 (34-66%), and 3 (67-100%). The expression of CL-1 or E-cad was considered "preserved" if the score in HCC was equal to or more than that in the surrounding hepatocytes, and "attenuated" if not so. RESULTS: In nontumorous tissue, CL-1 and E-cad were observed at the lateral surface of hepatocytes and biliary epithelial cells. In well-differentiated HCCs, the expression of CL-1 and E-cad was preserved in 12 of 14 cases. In poorly differentiated HCCs, E-cad expression was preserved in 9 of 18 cases, while CL-1 expression was preserved in only 4 cases (P<0.01 versus well-differentiated HCCs). HCCs with portal invasion showed significantly attenuated CL-1 expression than those without portal invasion (P<0.05). The survival rate after hepatectomy for HCC with attenuated CL 1 expression was significantly lower than that for HCC with preserved CL-1 expression. CONCLUSIONS: Attenuated expression of CL-1 closely correlates with the dedifferentiation and portal invasion of HCC. Down-regulated CL-1 expression may serve as a potential marker for a poor prognosis in HCC. PMID- 17270215 TI - TGFbeta1, TGFbeta2, and TGFbeta3 protein expression in gastric carcinomas: correlation with prognostics factors and patient survival. AB - BACKGROUND: This study evaluates the expression of transforming growth factors TGFbeta1, TGFbeta2 and TGFbeta3 in cases of gastric carcinoma and their possible correlation with classic prognostic markers and patient survival. MATERIALS AND METHODS: The study included 110 gastrectomy specimens obtained from equal number of patients with gastric cancer. According to the TNM classification, 7 tumors were identified as being stage I, 33 stage II, 52 stage III, and 18 stage IV, whereas 92 tumors were low-grade and 18 high-grade malignancies. On paraffin sections, the streptavidin-biotin technique using antibodies against TGFbeta1, TGFbeta2, and TGFbeta3 was applied. Morphological and immunohistochemical results were correlated with clinicopathologic parameters. RESULTS: TGFbeta1 was expressed in 78 out of 110 (71%) carcinomas, whereas TGFbeta2 and TGFbeta3 were detected in all tumors examined. Normal gastric mucosal epithelial cells expressed TGFbeta2 and TGFbeta3, but not TGFbeta1. Statistical analysis revealed higher expression of TGFbeta1 in low grade carcinomas (P = 0.009). TGFbeta2 presence was higher in advanced stage tumors (P = 0.008) and was correlated with worse prognosis (P < 0.05). TGFbeta1 expression was related to increased disease free survival (P < 0.05) while Cox analysis revealed that TGFbeta1 expression constituted an independent prognostic factor. CONCLUSIONS: Gastric carcinoma is related to differential expression of TGFbeta1, TGFbeta2, and TGFbeta3. TGFbeta1 may be implicated in the pathogenesis of the tumors, since it is expressed only in neoplastic tissue. TGFbeta1 is related with an increased disease-free and overall survival constituting an independent prognostic factor. In advanced stages, TGFbeta2 seems to be involved in tumor progression related to worse prognosis. PMID- 17270216 TI - Effects of gadolinium on regionally stunned myocardium: temporal considerations. AB - OBJECTIVES: The lanthanide cation, gadolinium (Gd(3+)), accelerates recovery of stunned myocardium when given prior to ischemia. This study sought to determine whether giving Gd(3+) during ischemia or during reperfusion also ameliorates stunning, as these temporal relationships could help determine the clinical utility of this novel agent. METHODS: Regional myocardial stunning was induced in anesthetized dogs by coronary occlusion for 15 min followed by reperfusion for 3 h. Gd(3+) (500 micromol) was given intravenously in three treatment groups: [1] preischemia; [2] during ischemia; [3] after reperfusion. No Gd(3+) was given to controls (Group 4). Measures of global and regional myocardial function were assessed serially. RESULTS: Treatment with Gd(3+) prior to ischemia (Group 1) had no effects on hemodynamics or regional contraction. Coronary occlusion resulted in diastolic lengthening and paradoxical systolic bulging equally in all groups. After 3 h of reperfusion, regional systolic shortening (%) in the stunned segment was greater in Groups 1 (10.9 +/- 3.4; P = 0.02) and 2 (6.6 +/- 1.3; P = 0.047) compared with controls (-0.6 +/- 0.03). Recovery of systolic function (% of baseline shortening) after 3 h of reperfusion was similarly improved in Groups 1 (56.1 +/- 16.8; P = 0.02) and 2 (43.3 +/- 8.1; P = 0.04) compared with controls ( 11.5 +/- 4.7). CONCLUSIONS: Gadolinium has no inherent inotropic effects but enhances recovery of stunned myocardium. This effect appears maximal if Gd(3+) is given prior to ischemia, indicating potential utility in elective cardiac surgical procedures or percutaneous coronary interventions. Gadolinium also enhances recovery if given during ischemia but prior to reperfusion, and may thus be useful in acute coronary syndromes as well. PMID- 17270218 TI - The effect of static and dynamic spatially structured disturbances on a locally dispersing population. AB - Previous models of locally dispersing populations have shown that in the presence of spatially structured fixed habitat heterogeneity, increasing local spatial autocorrelation in habitat generally has a beneficial effect on such populations, increasing equilibrium population density. It has also been shown that with large scale disturbance events which simultaneously affect contiguous blocks of sites, increasing spatial autocorrelation in the disturbances has a harmful effect, decreasing equilibrium population density. Here, spatial population models are developed which include both of these spatially structured exogenous influences, to determine how they interact with each other and with the endogenously generated spatial structure produced by the population dynamics. The models show that when habitat is fragmented and disturbance occurs at large spatial scales, the population cannot persist no matter how large its birth rate, an effect not seen in previous simpler models of this type. The behavior of the model is also explored when the local autocorrelation of habitat heterogeneity and disturbance events are equal, i.e. the two effects occur at the same spatial scale. When this scale parameter is very small, habitat fragmentation prevents the population from persisting because sites attempting to reproduce will drop most of their offspring on unsuitable sites; when the parameter is very large, large-scale disturbance events drive the population to extinction. Population levels reach their maximum at intermediate values of the scale parameter, and the critical values in the model show that the population will persist most easily at these intermediate scales of spatial influences. The models are investigated via spatially explicit stochastic simulations, traditional (infinite-dispersal) and improved (local-dispersal) mean-field approximations, and pair approximations. PMID- 17270217 TI - In-hospital onset ischemic stroke may be associated with atrial fibrillation and right-to-left shunt. AB - BACKGROUND AND PURPOSE: Ischemic stroke during hospitalization can occasionally be found, but the mechanisms and causes underlying stroke have not been investigated in detail. The present study aimed to identify differences in stroke etiology between in-hospital and out-of-hospital onset. METHODS: Subjects comprised 357 consecutive patients (221 men, 136 women) with ischemic stroke prospectively enrolled within 24 h of onset. Contrast saline transcranial Doppler ultrasonography (c-TCD) or transesophageal echocardiography (TEE) was performed in all participants to identify right-to-left shunts (RLS). Patients were divided into 2 groups: in-hospital onset (IHO group, n=49); and out-of-hospital onset (OHO group, n=308). Clinical characteristics were compared between groups. RESULTS: Mean age was 71.5+/-12.3 years. Mean National Institute of Health stroke scale score was 6.9+/-7.2. RLS, atrial fibrillation (AF) and malignancy were more frequent in the IHO group than in the OHO group (39% vs. 20%, p=0.006; 45% vs. 16%, p<0.001; 18% vs. 4%, p<0.001, respectively). AF and/or RLS was more frequent in the IHO group (61%) than in the OHO group (30%, p<0.001). CONCLUSION: Ischemic stroke with in-hospital onset may be associated with AF and RLS. PMID- 17270219 TI - Instabilities in multiserotype disease models with antibody-dependent enhancement. AB - This paper investigates the complex dynamics induced by antibody-dependent enhancement (ADE) in multiserotype disease models. ADE is the increase in viral growth rate in the presence of immunity due to a previous infection of a different serotype. The increased viral growth rate is thought to increase the infectivity of the secondary infectious class. In our models, ADE induces the onset of oscillations without external forcing. The oscillations in the infectious classes represent outbreaks of the disease. In this paper, we derive approximations of the ADE parameter needed to induce oscillations and analyze the associated bifurcations that separate the types of oscillations. We then investigate the stability of these dynamics by adding stochastic perturbations to the model. We also present a preliminary analysis of the effect of a single serotype vaccination in the model. PMID- 17270220 TI - Modeling regulation mechanisms in the immune system. AB - We develop a mathematical framework for modeling regulatory mechanisms in the immune system. The model describes dynamics of key components of the immune network within two compartments: lymph node and tissue. We demonstrate using numerical simulations that our system can eliminate virus-infected cells, which are characterized by a tendency to increase without control (in absence of an immune response), while tolerating normal cells, which are characterized by a tendency to approach a stable equilibrium population. We experiment with different combinations of T cell reactivities that lead to effective systems and conclude that slightly self-reactive T cells can exist within the immune system and are controlled by regulatory cells. We observe that CD8+ T cell dynamics has two phases. In the first phase, CD8+ cells remain sequestered within the lymph node during a period of proliferation. In the second phase, the CD8+ population emigrates to the tissue and destroys its target population. We also conclude that a self-tolerant system must have a mechanism of central tolerance to ensure that self-reactive T cells are not too self-reactive. Furthermore, the effectiveness of a system depends on a balance between the reactivities of the effector and regulatory T cell populations, where the effectors are slightly more reactive than the regulatory cells. PMID- 17270222 TI - Distinct patterns of olfactory impairment in Alzheimer's disease, semantic dementia, frontotemporal dementia, and corticobasal degeneration. AB - Performance on tests of odour discrimination, naming, and matching was compared in patients with four distinct forms of neurodegenerative disease: Alzheimer's disease (AD), semantic dementia (SD), frontotemporal dementia (FTD), and corticobasal degeneration (CBD). The SD patients were found to have a severe impairment of identification from olfaction despite having normal discrimination, consistent with the multimodal semantic impairment characteristic of this patient group. The AD patients' poor odour discrimination suggests that a perceptual impairment is the root of their poor odour identification. Mild impairments in odour identification observed in FTD and CBD are consistent with their generalised executive dysfunction. The findings illustrate that breakdown in olfaction can occur at a perceptual or semantic level, analogous to the distinction between apperceptive and associative forms of deficit in the visual and auditory modalities. The findings add further insights into the nature of the semantic deficit in SD by exploring a hitherto neglected modality and may have relevance in explaining the altered eating habits commonly associated with SD. PMID- 17270223 TI - Does intestinal absorption participate in the ponderostat? AB - Body weight regulation is known to achieve energy balance through several responses: appetite, satiety, thermogenesis, feeding behavior. Absorption efficiency might be, also, another response. In this paper, we hypothesized that the intestinal absorption efficiency of the rat might be lowered in response to a high energy content of the diet. Thirty-one rats were assigned to a specific diet (restricted, control, and cafeteria) during three weeks. Rats' body mass, BMI, and body fat were measured and absorption efficiency was calculated through the ratio of energy ingested/energy defecated. Intestinal histology was examined post mortem. Absorption efficiency was not lower in cafeteria groups but was higher than in control and restricted rats. No histological difference was seen after the various diets. Such results indicate that intestinal absorption is working at full efficiency whatever the diet, and is not a regulatory response contributing to the ponderostat. PMID- 17270221 TI - DNA content and chromatin texture of human breast epithelial cells transformed with 17-beta-estradiol and the estrogen antagonist ICI 182,780 as assessed by image analysis. AB - The immortalized human breast epithelial MCF-10F cell line, although estrogen receptor alpha negative, develops cell proliferating activities and invasiveness indicative of neoplastic transformation, after treatment with 17-beta-estradiol (E-2). These effects are similar to those produced by benzo[a]pyrene (BP). Since we have previously reported changes in the nuclear parameters accompanying BP induced tumorigenesis in MCF-10F cells, we have examined whether similar alterations occur in E-2-treated cells. We therefore studied DNA amounts and other nuclear parameters in Feulgen-stained MCF-10F cells after treatment with various concentrations of E-2, BP, the estrogen antagonist ICI 182,780, and E-2 in the presence of ICI 182,780. E-2 caused a certain loss of DNA and changes in the nuclear size and chromatin supraorganization of MCF-10F cells. Many of these changes were similar to those produced by BP and were indicative of neoplastic transformation. More intense chromatin remodelling was seen with 70 nM E-2. Since these changes were not abrogated totally or partially by ICI 182,780, the neoplastic transformation of MCF-10F cells stimulated by E-2 involved a process that was independent of estrogen alpha-receptors. The changes produced by ICI 182,780 alone were attributed to effects other than its well-known anti estrogenic activity. PMID- 17270224 TI - alpha-Glucosidase inhibitory pentacyclic triterpenes from the stem bark of Fagara tessmannii (Rutaceae). AB - In addition to fatty acids, a mixture of sterols (beta-sitosterol, stigmasterol, campesterol and stigmastanol), lupeol, arctigenin methylether, sesamin, vanillic acid (1), 2,6-dimethoxy-1,4-benzoquinone (2), betulinic acid and two pentacyclic triterpene acetates were isolated from Fagara tessmannii Engl. They were identified as 3beta-acetoxy-16beta-hydroxybetulinic acid (3a) and 3beta,16beta diacetoxybetulinic acid (3b), and their structures were established using 1 and 2D NMR spectra and by comparison with published data. Two derivatives of the compounds were prepared. Some isolated compounds were evaluated for their antifungal and antibacterial activities. Compounds 1 and 3a showed significant inhibition of alpha-glucosidase. PMID- 17270225 TI - Structure activity studies with xenobiotic substrates using carboxylesterases isolated from Arabidopsis thaliana. AB - Carboxylesterases (CXEs) catalyse the hydrolysis of xenobiotics and natural products radically altering their biological activities. Whereas the substrate selectivity of animal CXEs, such as porcine liver esterase (PLE) have been well studied, the respective enzymes in plants have yet to be defined and their activities determined. Using Arabidopsis thaliana (At) as a source, five representative members of the alpha/beta hydrolase AtCXE family of proteins have been cloned, expressed and the purified recombinant proteins assayed for esterase activity with xenobiotic substrates. Two members, AtCXE5 and AtCXE18 were found to be active carboxylesterases, though AtCXE5 proved to be highly unstable as a soluble protein. AtCXE18 and the previously characterised S-formylglutathione hydrolase from Arabidopsis (AtSFGH) were assayed against a series of esters based on methylumbelliferone in which the acyl moiety was varied with respect to size and conformation. The same series was used to assay crude esterase preparation from Arabidopsis plants and the results compared with those obtained with the commonly used PLE. With straight chain esters, AtCXE18 behaved like PLE, but the Arabidopsis hydrolases proved less tolerant of branched chain acyl components than the mammalian enzyme. While none of the enzyme preparations accurately reflected all the activities determined with crude Arabidopsis protein extracts, the plant enzymes proved more useful than PLE in predicting the hydrolysis of the more sterically constrained esters. PMID- 17270226 TI - Interpreting tests for iron deficiency among adults in a high HIV prevalence African setting: routine tests may lead to misdiagnosis. AB - We evaluated peripheral blood tests to diagnose iron deficiency on medical wards in Blantyre, Malawi, where infection and HIV are prevalent. We compared full blood count, ferritin and serum transferrin receptor (TfR) levels with an estimation of iron in bone marrow aspirates. Of consecutive adults admitted with severe anaemia (haemoglobin <7 g/dl), 81 had satisfactory bone marrow aspirates. The main outcome measures were the validity of each test (sensitivity, specificity, and positive and negative predictive values) and likelihood ratios (LR) for iron deficiency. Twenty patients (25%) were iron deficient and 64 (79%) were HIV-positive. Iron deficiency was more common in HIV-negative compared with HIV-positive patients (59% vs. 16%; P<0.001). In HIV-positive patients, the optimal ferritin cut-off was 150 microg/l (sensitivity 20%, specificity 93%, LR 2.7), but no test was accurate enough to be clinically useful. In HIV-negative patients, ferritin was the single most accurate test (cut-off <70 microg/l, 100% specificity, 90% sensitive, LR if positive infinity, LR if negative 10). TfR measurement did not improve the accuracy. Mean cell volume was not a good predictor of iron status except in HIV-negative patients (cut-off <85 fl, specificity 71%, sensitivity 90%). In populations with high levels of infection and HIV, an HIV test is necessary to interpret any tests of iron deficiency. In HIV-negative patients, ferritin is the best blood test for iron deficiency, using a higher cut-off than usual. For HIV-positive patients, it is difficult to diagnose iron deficiency without bone marrow aspirates. PMID- 17270227 TI - Human African trypanosomiasis: diagnosis, relapse and survival after severe melarsoprol-induced encephalopathy. AB - We describe a case of human African trypanosomiasis with a number of unusual features. The clinical presentation was subacute, but the infection was shown to be due to Trypanosoma brucei rhodesiense. The infection relapsed twice following treatment and the patient developed a melarsoprol-associated encephalopathy. Magnetic resonance imaging (MRI) findings were suggestive of microhaemorrhages, well described in autopsy studies of encephalopathy but never before shown on MRI. The patient survived severe encephalopathy with a locked-in syndrome. Our decision to provide ongoing life support may be useful to physicians treating similar cases in a setting where intensive care facilities are available. PMID- 17270228 TI - Amplification due to spatial clustering in an individual-based model of mosquito avian arbovirus transmission. AB - Theory and observations indicate that spatial clustering of birds and mosquitoes may be necessary for epizootic amplification of arboviruses with avian zoonoses. In this paper, I present an individual-based model of zoonotic arbovirus transmission among birds and mosquitoes. The results of initial ensemble model simulations indicate that the co-location of a vector mosquito oviposition site with an infected bird roost increases the local vector-to-host density and increases the likelihood of arbovirus amplification within the infected roost. Such amplification also increases the likelihood of secondary amplification at other roost sites, produces higher vector and host infection rates, increases the time to virus extinction within the model population, and increases the total number of birds infected. Additional oviposition locations within the model domain also increase the likelihood of secondary amplification. These findings support the idea that spatial clustering of mosquitoes and birds may facilitate arbovirus amplification. This model provides a basis for future exploration of specific zoonotic transmission cycles, including West Nile virus, and could be used to test the efficacy of various control strategies. PMID- 17270230 TI - Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells. AB - The transcription/replication activity of ribonucleoproteins derived from influenza A primary isolates of human (A/Paris/908/97) or avian origin (A/Mallard/Marquenterre/MZ237/83, A/Hong Kong/156/97) was compared upon reconstitution in mammalian or avian cells, using viral-like reporter RNAs synthesized under the control of the human and chicken RNA polymerase I promoters, respectively. In avian cells, transcription/replication activities were in the same range with all ribonucleoproteins tested. In human cells, ribonucleoproteins derived from A/Mallard/Marquenterre/MZ237/83 showed reduced transcription/replication activity and reduced NP binding to the PB1-PB2-PA complex (P) or to the isolated PB2 subunit, as compared to the ribonucleoproteins derived from A/Paris/908/97. Both defects were restored when PB2 residue Glu-627 was changed to a Lys. Ribonucleoproteins derived from the human A/Hong Kong/156/97 H5N1 isolate showed efficient NP-P interaction in human cells, and high levels of activity which were determined mostly by the PB2 and PA proteins. Our data suggest that PB2 might play a pivotal role in molecular interactions involving both the viral nucleoprotein and cellular proteins. PMID- 17270232 TI - Naphthoquinones as broad spectrum biocides for treatment of ship's ballast water: toxicity to phytoplankton and bacteria. AB - Current UN International Maritime Organization legislation mandates the phased introduction of ballast water treatment technologies capable of complying with rigorous standards related to removal of waterborne organisms. Doubts concerning mechanical treatments at very high ballasting rates have renewed interest in chemical treatment for very large vessels. High removal rates for biota require broad spectrum biocides that are safe to transport and handle and pose no corrosion problems for ships' structure. The current study focuses on the naphthoquinone group of compounds and extends a previously reported set of screening bioassays with an investigation of the toxicity of four naphthoquinones to select protists and prokaryotes, representative of typical ballast water organisms. Vegetative dinoflagellate cysts exposed to 2.0 mg/L of the naphthoquinones juglone, plumbagin, menadione and naphthazarin showed varying degrees of chloroplast destruction, with menadione demonstrating the most potency. Laboratory and mesocosm exposures of various phytoplankton genera to menadione showed toxicity at 1.0 mg/L. Juglone demonstrated the most bactericidal activity as judged by a Deltatox assay (Vibrio fischeri) and by acridine orange counts of natural bacterial populations. PMID- 17270231 TI - Isolation and characterization of mouse-human microcell hybrid cell clones permissive for infectious HIV particle release. AB - Mouse cells are non-permissive to human immunodeficiency virus type 1 (HIV) in that there is a pronounced post-integration block to viral replication. We have recently demonstrated that mouse-human somatic cell hybrids that contain human chromosome 2 increase both HIV Capsid (CA) production and infectious virus release. Here we report on the isolation of three mouse-human microcell hybrids (MCHs) that behave similarly, starting from a pool of 500 MCH clones. Release of virus was specific to HIV and cell revertants that no longer contained any human chromosome fragments did not release CA or infectious virus. Two of the three cell clones were identical as judged by PCR STS content and fluorescence in situ hybridization (FISH) and contained a single 2-12 human chromosome chimera. The third cell clone only contained human chromosome 12, as determined by PCR, FISH, and microarray analyses. There were no consistent differences in Gag protein and spliced/unspliced viral RNA levels between mouse cell lines. CMV promoter-driven, codon-optimized gag-pol had no effect on infectious HIV release from these mouse cells, despite allowing Gag targeting and increasing CA production. These permissive mouse-human MCHs and their corresponding non-permissive revertants may prove useful for mechanistic studies and also for identifying the responsible gene(s) or factor(s) involved in the production of HIV. PMID- 17270229 TI - p53 and the pathogenesis of skin cancer. AB - The p53 tumor suppressor gene and gene product are among the most diverse and complex molecules involved in cellular functions. Genetic alterations within the p53 gene have been shown to have a direct correlation with cancer development and have been shown to occur in nearly 50% of all cancers. p53 mutations are particularly common in skin cancers and UV irradiation has been shown to be a primary cause of specific 'signature' mutations that can result in oncogenic transformation. There are certain 'hot-spots' in the p53 gene where mutations are commonly found that result in a mutated dipyrimidine site. This review discusses the role of p53 from normal function and its dysfunction in pre-cancerous lesions and non-melanoma skin cancers. Additionally, special situations are explored, such as Li-Fraumeni syndrome in which there is an inherited p53 mutation, and the consequences of immune suppression on p53 mutations and the resulting increase in non-melanoma skin cancer in these patients. PMID- 17270233 TI - Towards measuring particle-associated fecal indicator bacteria in tropical streams. AB - A protocol to enumerate particle-associated microbial indicator bacteria (heterotrophic plate count [HPC], enterococci [ENT] and Clostridium perfringens [CP]) by membrane filtration in a tropical stream is proposed that relies on high speed homogenization and chemical treatment. Application of this protocol to stream samples suggest that ENT measurements are more biased by the presence of aggregates than HPC or CP. Whole sample treatment typically increased the colony forming units (CFU) count by 9-52%. Analysis of different settled fractions and examination of the number of indicators recoverable from particles retained on a 5 microm filter in relation to the number of particles containing target indicators both indicate that relatively more ENT form aggregates than HPC or CP. Although the bias is smallest for CP, this does not imply that CP is a better indicator as this depends on the unknown extent to which pathogens are themselves found associated with particles. PMID- 17270234 TI - Factors affecting formation of haloacetonitriles, haloketones, chloropicrin and cyanogen halides during chloramination. AB - Effects of contact time, monochloramine doses, monochloramine application modes, pH, temperature and bromide ion concentrations on formation of disinfection by products (DBPs), including haloacetonitriles, haloketones, chloropicrin, cyanogen halides and trihalomethanes, during chloramination were investigated using model solutions containing 5 mg/L (as DOC) Suwannee River natural organic matter (NOM). Chloramine speciation and some DBPs were measured using membrane introduction mass Spectrometer (MIMS). Longer reaction times led to continued formation over time for dichloroacetonitrile (DCAN), 1,1-dichloro-2-propanone (1,1-DCP) and chloroform. Cyanogen chloride (CNCl) formation occurred over time, but after reaching a peak concentration CNCl concentrations decreased over longer time periods. Linear relationships were observed between the formation of DCAN, 1,1 DCP, CNCl or chloroform and the dosage of monochloramine. Chloramination modes (addition of preformed monochloramine or variable sequential additions of free chlorine and ammonium salts) exhibited the largest impact on chloroform formation but displayed little effect on the formation of DCAN, 1,1-DCP and CNCl. Over the range in pH from 4 to 9 profound differences in DBP formation were observed; pH values between 5 and 6 resulted in the highest DBP concentrations. An increase in temperature enhanced the formation of chloroform but did not affect DCAN, 1,1-DCP and CNCl formation. Chloropicrin concentrations were always low (around detection limits) under all conditions. Increasing the concentrations of bromide ions enhanced the formation of bromine-substituted DBPs. PMID- 17270236 TI - Sonochemical substrate selectivity and reaction pathway of systematically substituted azo compounds. AB - The sonochemical degradation of the systematically substituted azo compound 2,7 dihydroxy-1-phenylazonaphthaline-3,6-disulfonic acid was investigated using a frequency of 850 kHz and an acoustic input power of 61 W. All derivatives were degraded completely within 6h by the ultrasonic treatment. Trifluoromethyl substituted azo compounds exhibited 2-3-fold higher degradation rates in comparison to the reference hydrogen substituted azo compound (k=0.54 h(-1)). In contrast to enzymatic processes (azoreductase or laccase), the ultrasonic treatment for these ortho-, meta-, and para-substituted azo compound showed 1.5 50-fold higher degradation rates. Additionally the ultrasound treatment was characterized by shorter reaction times. As a result of the detection and identification of specific intermediates using LC-MS a reaction pathway of the sonochemical degradation of the analysed azo compound is proposed indicating the formation of cyclohexadienone and naphthalene quinone derivatives. PMID- 17270237 TI - Establishment and validation of primary hepatocytes of the African sharptooth catfish (Clarias gariepinus). AB - In vitro systems such as primary cells and continuous cell lines are gaining momentum in ecotoxicological studies. Cytotoxicity tests with fish cells as well as tests using specific endpoints such as CYP1A induction are valuable in the toxicity assessment of environmental samples. The main objective of this study was to establish and validate the use of primary hepatocytes from the African sharptooth catfish (Clarias gariepinus) as an in vitro toxicity monitoring system. The successful isolation of primary hepatocytes from the sharptooth catfish was achieved using an in situ perfusion method. The primary hepatocytes responded to CYP1A induction, while a continuous Chinese hamster ovary (CHO-K1) cell line showed no activity when exposed to various concentrations of benzo[a]pyrene (B[a]P) (p<0.0001). Cytotoxicity, as measured by the methyl thiazol tetrazolium (MTT) assay, was not observed following a 72 h exposure of the primary hepatocytes and the CHO-K1 cell line to different B[a]P concentrations. However, the hepatocytes were damaged at higher B[a]P concentrations (>10(-6)M) as shown by transmission electron microscopy. This cytotoxicity effect was also confirmed by the trypan blue exclusion assay (TD(50) of 10(-6)M). Differences in the results between the MTT and trypan blue exclusion assays are probably due to mitochondria that are still metabolically active, causing the tetrazolium salt to be dehydrogenated. The internal architecture of normal primary hepatocytes included large quantities of rough endoplasmic reticulum (often in close proximity to the nucleus), mitochondria, aggregates and scattered glycogen, a few lipid droplets and spherical nuclei with distinct nucleoli. The primary catfish hepatocyte cell culture system, expressing CYP1A when exposed to B[a]P, could be used as a biomarker for aromatic hydrocarbon pollutants in aquatic ecosystems of southern and East Africa. PMID- 17270235 TI - Synthesis and antiviral activities of new acyclic and "double-headed" nucleoside analogues. AB - To develop an understanding of the structure-activity relationships for the inhibition of orthopoxviruses by nucleoside analogues, a variety of novel chemical entities were synthesized. These included a series of pyrimidine 5 hypermodified acyclic nucleoside analogues based upon recently discovered new leads, and some previously unknown "double-headed" or "abbreviated" nucleosides. None of the synthetic products possessed significant activity against two representative orthopoxviruses; namely, vaccinia virus and cowpox virus. They were also devoid of significant activity against a battery of other DNA and RNA viruses. So far as the results with the orthopoxviruses and herpes viruses, the results may point to the necessity for nucleoside analogues 5'-phosphorylation for antiviral efficacy. PMID- 17270238 TI - Assessment of toxicity of a glyphosate-based formulation using bacterial systems in lake water. AB - A new Aeromonas bioassay is described to assess the potential harmful effects of the glyphosate-based herbicide, Roundup, in the Albufera lake, a protected area near Valencia. Viability markers as membrane integrity, culturability and beta galactosidase production of Aeromonas caviae were studied to determine the influence of the herbicide in the bacterial cells. Data from the multifactor analysis of variance test showed no significant differences (P>0.05) between A. caviae counts of viability markers at the studied concentrations (0, 50 and 100 mg l-1 of glyphosate). The effects of Roundup on microbial biota present in the lake were assessed by measuring the number of indigenous mesophilic Aeromonas in presence of different amounts of the herbicide at 0, 50 and 100 mg l-1 of glyphosate. In samples containing 50 and 100 mg l-1 of glyphosate a significant (P<0.05) increase in Aeromonas spp. counts and accompanying flora was observed. The acute toxicity of Roundup and of Roundup diluted with Albufera lake water to Microtox luminescent bacterium (Vibrio fischeri) also was determined. The EC50 values obtained were 36.4 mg l-1 and 64.0 mgl-1 of glyphosate respectively. The acidity (pH 4.5) of the herbicide formulation was the responsible of the observed toxicity. PMID- 17270239 TI - TGFBR2 mutation is correlated with CpG island methylator phenotype in microsatellite instability-high colorectal cancer. AB - The transforming growth factor-beta receptor type 2 gene (TGFBR2) is mutated in most microsatellite instability-high (MSI-H) colorectal cancers. Promoter methylation of RUNX3 (runt-related transcription factor 3; encoding a transcription factor downstream of the TGF-beta pathway) is observed in colorectal cancer with CpG island methylator phenotype (CIMP), which is characterized by extensive promoter methylation and is associated with MSI-H and BRAF mutations. However, no study to date has examined interrelationship between TGFBR2 mutation, RUNX3 methylation, and CIMP in colorectal cancer. Using 144 MSI H colorectal cancers derived from 2 large prospective cohort studies, we analyzed a mononucleotide repeat of TGFBR2 and quantified DNA methylation (by MethyLight technology) in 8 CIMP-specific promoters (RUNX3, CACNA1G [calcium channel, voltage-dependent, T type alpha-1G subunit], CDKN2A [p16], CRABP1 [cellular retinoic acid binding protein 1], IGF2 [insulin-like growth factor 2], MLH1, NEUROG1 [neurogenin 1], and SOCS1 [suppressor of cytokine signaling 1]). Among the 144 MSI-H tumors, the presence of TGFBR2 mutation (overall 72% frequency) was correlated positively with CIMP-high (with >/=6/8 methylated promoters; P < .0001), RUNX3 methylation (P = .0004), BRAF mutation (P = .0006), and right colon (P = .05); inversely with KRAS mutation (P = .006); but not significantly with sex, tumor differentiation, and p53 status (assessed by immunohistochemistry). After stratification by sex, location, tumor differentiation, RUNX3 status, KRAS/BRAF status, or p53 status, CIMP-high was persistently correlated with TGFBR2 mutation. In contrast, RUNX3, KRAS, or BRAF status was no longer correlated with TGFBR2 mutation after stratification by CIMP status. In conclusion, TGFBR2 mutation is associated with CIMP-high and indirectly with RUNX3 methylation. Our findings emphasize the importance of analyzing global epigenomic status (for which CIMP status is a surrogate marker) when correlating a single epigenetic event (eg, RUNX3 methylation) with any other molecular or clinicopathologic variables. PMID- 17270240 TI - Feasibility and diagnostic agreement in teledermatopathology using a virtual slide system. AB - We investigated the feasibility and diagnostic agreement of a virtual slide system (VSS) in teledermatopathology. Forty-six biopsy specimens from inflammatory skin diseases were selected and scanned with a VSS at the Research Unit of Teledermatology, Medical University of Graz, Graz, Austria. Images were stored on a virtual slide server on which a specific Web application suited for telepathology (http://telederm.org/research/dermatopath/) runs. Twelve teleconsultants from 6 different countries reviewed the 46 cases, working directly on the Web application. Telediagnoses agreed with gold standard and conventional diagnosis with an average of 73% and 74%, respectively. Complete concordance among all teleconsultants with gold standard and conventional diagnosis was found in 20% of the cases. In 10 cases in which complete clinical data were missing, the average agreement of telediagnosis with gold standard diagnosis and conventional diagnosis decreased to 65% and 66%, respectively. Only 3 of 4 cases of inflammatory skin diseases were correctly diagnosed remotely with VSS. The system that we have used, despite its usability, is not completely feasible for teledermatopathology of inflammatory skin disease. Moreover, the performance seems to have been influenced by the availability of complete clinical data and by the intrinsic difficulty of the pathology of inflammatory skin diseases. PMID- 17270241 TI - Conventional renal cancer in a patient with fumarate hydratase mutation. AB - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome caused by mutations in the fumarate hydratase (FH) gene. HLRCC is characterized by uterine and cutaneous leiomyomas, renal cell cancer, and uterine leiomyosarcoma. Typically, renal cell cancers in HLRCC are unilateral and display a papillary type 2 or ductal histology. We describe here a 23-year-old patient carrying a novel FH mutation (N330S) with a bilateral renal cell center. Carcinoma of the right kidney showed papillary structure, but the left tumor was diagnosed as a conventional (clear cell) renal carcinoma, a type not previously described in HLRCC. The clear cell renal carcinoma also displayed loss of the normal FH allele and the FH immunostaining. Our finding extends the number of cases in which HLRCC can be suspected, and the FH immunohistochemistry may serve as a useful tool to screen for HLRCC in young individuals with clear cell renal carcinoma. PMID- 17270242 TI - Angioleiomyoma: a clinicopathologic and immunohistochemical reappraisal with special reference to the correlation with myopericytoma. AB - In spite of the histologic overlap, the relationship between angioleiomyoma and myopericytoma has not yet been fully evaluated. One hundred thirty lesions originally diagnosed as angioleiomyoma and 4 tumors identified as myopericytoma were reassessed both histologically and immunohistochemically. One hundred twenty two tumors were thus reclassified as angioleiomyoma (74 solid, 37 venous, and 11 cavernous types) and 12 as myopericytoma based on the predominant histologic pattern. In 1 patient, 1 myopericytoma and 1 venous-type angioleiomyoma were synchronously present. The perivascular concentric arrangement of cells, which is a salient feature of myopericytoma, was also focally recognized in 19 angioleiomyomas (12 venous, 4 solid, and 3 cavernous types). An angioleiomyoma like fascicular pattern of elongated myoid cells was partially present in 7 myopericytomas, 4 of which resembled the feature of the cavernous subtype and 3 the venous one. Immunohistochemically, most tumor cells of all cases of both angioleiomyomas and myopericytomas were diffusely positive for actins (alpha smooth muscle actin and HHF35) and calponin, and all cases, except for 1 myopericytoma, were also diffusely or focally positive for h-caldesmon. Desmin was diffusely positive in 75.7% of solid-type angioleiomyomas, 51.4% of venous type, and 18% of cavernous type, whereas most of the myopericytomas were negative for desmin, even though desmin-positive cells were only partially seen in 3 myopericytomas. The concentric structures of myoid cells in angioleiomyomas were, however, consistently negative for desmin. Our data further support the close kinship between angioleiomyoma and myopericytoma that has been recently suggested. PMID- 17270244 TI - Recommendations for the reporting of fallopian tube neoplasms. AB - Primary malignancies of the fallopian tube are extremely uncommon, in part due to (admittedly arbitrary) definitional criteria. By convention, epithelial tumors that involve the ovary or peritoneal surfaces are considered to have arisen either in the ovary or endometrium or, in absence of significant ovarian or endometrial involvement, in the peritoneum, irrespective of whether or not the fallopian tube mucosa is also involved. Evidence from the World Health Organization and more recently, from case-control studies of BRCA mutation carriers suggests the fallopian tube may have a more direct role in the development of at least some of these carcinomas. An alternative hypothesis for the origin of ovarian and peritoneal carcinoma has even been proposed, based on the concept of transport and implantation of malignant cells from the tube to the ovary and peritoneum. Malignancies in the fallopian tube can therefore be classified as (1) arising primarily in the fallopian tube, either from preexisting endometriosis (or more rarely, a mature teratoma) or directly from tubal mucosa with metastasis to adjacent tissues; (2) arising in the ovary, endometrium, or peritoneum with metastasis to the tubal serosa or mucosa; or (3) arising primarily in the fallopian tube as well as in the ovary, endometrium, or peritoneum (simultaneous primary tumors). Since there are currently no evidence based criteria for distinguishing primary tubal carcinoma from primary ovarian or primary endometrial carcinoma in patients with high stage disease, the Association of Directors of Anatomic and Surgical Pathology recommended strategies for assignment of site of origin are based on current standard practices. PMID- 17270243 TI - Simultaneous occurrence of peripheral T-cell lymphoma unspecified and B-cell small lymphocytic lymphoma. Report of 2 cases. AB - We report on 2 composite lymphomas occurring in elderly patients, morphologically characterized by the combination of peripheral T-cell lymphoma (PTCL) unspecified and B-cell small lymphocytic lymphoma. Immunohistochemistry provided objective confirmation of the coexistence of the 2 malignancies, as did molecular biology by revealing clonal T-cell receptor gamma and immunoglobulin heavy chain gene rearrangements. One of the patients had no history of indolent lymphoma either at the personal and family level, whereas the other showed a strong familial predisposition, his mother and sister having suffered from B-cell chronic lymphocytic leukemia. Epstein-Barr virus was detected in the PTCL component of 1 case, but was negative in the other. To the best of our knowledge, the simultaneous occurrence of PTCL unspecified and B-cell small lymphocytic lymphoma is an exceptional event; the possible pathogenetic correlations between the 2 neoplasms are discussed. PMID- 17270245 TI - RET oncogene amplification in thyroid cancer: correlations with radiation associated and high-grade malignancy. AB - A radiation etiology is well known in thyroid carcinogenesis. RET oncogene rearrangement is the most common oncogenic alteration in Chernobyl-related papillary thyroid cancer (PTC). To find the characteristic alteration associated with RET rearrangements in radiation-induced thyroid cancers, we analyzed the RET oncogene by fluorescence in situ hybridization. The fluorescence in situ hybridization technique has the possibility of detecting RET rearrangements at a single-cell level regardless of the specific fusion partner involved and directly reveals RET copy number on a per-cell basis. Our study demonstrated RET amplification in all 3 cases of radiation-associated thyroid cancers but not in sporadic well-differentiated PTC (n = 11). Furthermore, RET amplification was observed in all 6 cases of sporadic anaplastic thyroid cancers (ATCs). The frequency of RET amplification-positive cells was higher in ATC (7.2%-24.1%) than in PTC (1.5%-2.7%). The highest frequency of RET amplification-positive cells was observed among ATC cases with a strong p53 immunoreactivity. In conclusion, we found RET amplification, which is a rare oncogenic aberration, in thyroid cancer. This report is the first one to suggest the presence of RET amplification in PTC and ATC. RET amplification was correlated with radiation-associated, high-grade malignant potency, and p53 accumulation, suggesting genomic instability. RET amplification might be induced by a high level of genomic instability in connection with progression of thyroid carcinogenesis and, subsequently, be associated with radiation-induced and/or high-grade malignant cases. PMID- 17270246 TI - Recommendations for the reporting of surgically resected specimens of colorectal carcinoma. AB - The reporting of colorectal cancer is facilitated by the provision of a checklist giving the features required for good patient care. However, the practicalities of applying such a checklist may not be straightforward. Familiar examples include finding the prescribed number of lymph nodes, distinguishing mesenteric tumor deposits from replaced lymph nodes, and deciding if a cluster of malignant cells in a lymph node sinus counts as metastasis. Checklists have traditionally focused on prognostic factors and, particularly, tumor stage. It is becoming increasingly clear that additional factors, whether morphological or molecular, will be needed for future clinical management. It is also evident that prognosis is strongly influenced by the surgical technique used, most notably by the introduction of total mesorectal excision in the case of rectal cancer. Adjuvant therapy is playing an increasingly important role in the management of colorectal cancer, and it is inevitable that morphological and molecular markers will be used to predict responses to the expanding range of therapeutic modalities. Neoadjuvant or preoperative radiotherapy is being offered to patients with advanced rectal cancer and can greatly modify the pathologic findings in operative specimens. For all the preceding reasons, the work of diagnostic pathologists has become increasingly complex and demanding. The 6th edition of the TNM classification fails to meet many of the challenges posed by the realities of modern cancer management. In fact, by changing the rules for staging without strong justification and introducing diagnostic criteria that are unhelpful and lack a good evidence base, there is a real danger that the community of pathologists will fail to engage with reporting recommendations in a standardized manner and that the quality of reporting will decline. PMID- 17270247 TI - Age-related changes in mitochondrial function and antioxidative enzyme activity in fischer 344 rats. AB - We have previously reported the changes of mitochondrial function and/or antioxidative enzyme efficiency in a few organs of rats as a result of aging. However, there is a further need to reach a conclusion about their interactions in biological functions based on other evaluation tips like the usage of advanced methods and the exploring of crucial biochemical parameters. Therefore, we investigated the mitochondrial inner membrane functional integrity by the analysis of respiration control ratio and membrane potential in the liver and brain of young (8 months) and old (26 months) Fischer 344 rats. The disintegration of mitochondrial membrane integrity was determined higher in the liver of old rats than that of young rats. This was well correlated with the decrease of total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase activities in most of the organs, except for the increase of catalase activity in heart of old rats. Similarly, the protein expressions of these enzymes were down regulated in the liver and kidney of old rats. Taken together, we suggest that the mitochondrial malfunction in old rats is associated with the decrease of antioxidative enzyme efficiency. And the data are also discussed with changes in the results from inter-laboratories. PMID- 17270248 TI - Dietary exposure to copper in the European Union and its assessment for EU regulatory risk assessment. AB - EU legislation requires a multimedia exposure assessment for substances supplied within the EU. Dietary intake is the main source of exposure for the majority of the population hence an essential component of the human risk assessment. This paper describes the available data for dietary copper and its use in estimating daily intake including variability and determinants of exposure. Typical and reasonable worst-case estimates are derived for the general population from the available peer reviewed literature. Intakes from drinking water are found to exhibit more variability than those from food. Therefore, different exposure scenarios are derived to reflect the range of acute and chronic exposures that may occur. Estimates of typical copper intakes for the EU population are in the range 0.8-1.8 mg/day. Typical copper intakes of men are higher than those of women while the intake among the general adult population is higher than that of the elderly. Intakes of both men and women are generally close to the WHO normative requirements but may be somewhat lower in specific locations where background levels of copper are unusually low. Alcoholic beverages represent minor contribution daily copper intakes. Intakes for children are rather variable ranging broadly from 0.7 to 1.5 mg/day and are somewhat age and sex dependent. Greater uncertainty applies to the assessment of local exposure incorporating food produced on land directly impacted by contemporary copper industry emissions. Specifically, the extent to which soil is enriched in copper in these conditions is unclear. However, effective homeostatic control mechanisms in plants limit uptake and transfer to the human food chain. A best estimate of 0.25 mg/day in addition to regional exposure was derived. Drinking water is estimated to contribute only marginally to total copper intake in most cases. Higher intakes may occur in areas of poor water quality and/or corroded distribution systems. Such elevated exposures appear unusual but their frequency is unknown. PMID- 17270249 TI - Feeding the city: food consumption and flow of nitrogen, Paris, 1801-1914. AB - The flows of foodstuffs (and the nitrogen they contain) through the city of Paris in the 19th and early 20th century were evaluated. Between 1801 and 1914, the fivefold increase in the population of Paris, as well as the threefold increase in the number of horses used in urban transport, gave rise to increased needs for food and feed. The corresponding inputs of nitrogen increased from 6000 tN/year in 1817 to 25,000 tN/year from the rural hinterland to the city. The corresponding per capita inflows were relatively stable throughout the period and may be divided into four more or less equal parts (flour, meat, other human foodstuffs, forage), each representing about 6 gN per inhabitant per day. In total, the demand for foodstuffs was of the order of 24 gN per inhabitant per day, one quarter of which was for transport. The fate of this dietary nitrogen after consumption changed a lot with the techniques used for exploiting urban excreta of all kinds, particularly of nitrogen, which was in great demand until the development of synthetic fertilizers. Dietary nitrogen flow diagrams are established for the years 1817, 1869 and 1913, and reveal an increasing improvement of the agricultural reuse (from 20 to 40% of the inflowing N). PMID- 17270250 TI - Five year water and nitrogen balance for a constructed surface flow wetland treating agricultural drainage waters. AB - The performance of a constructed surface flow wetland in reducing diffuse N pollution coming from croplands is being investigated in an ongoing experiment, begun in 1998 in NE Italy. The 0.32 ha wetland is vegetated with Phragmites australis (Cav.) Trin. and Typha latifolia (L.). It receives drainage water from 6 ha of land managed for an experiment on drainage systems, where maize, sugarbeet, winter wheat and soybean are cultivated. During the period 1998-2002, the wetland received from 4698 to 8412 mm of water per year (on average, about 9 times the environmental rainfall); its water regimen was discontinuous and flooding occurred on a variable number of days per year (from 13 to 126). Nitric nitrogen was the most important form of element load. Its concentration in the inflow water over time was rather discontinuous, with median values ranging from 0.2 (in 2001) to 4.5 (in 2000) mg L(-1). Inflow nitric N concentrations were occasionally in the 5-15 mg L(-1) range. Concentrations reduced passing through the wetland, with a more evident effect in the last year. Over 5 years, the wetland received slightly more than 2000 kg ha(-1) of nitrogen, 87% in nitric form mostly from farmland drainage. The remaining 13% of N was applied as organic slurry directly onto the wetland, with 5 distributions during 1998 to assess wetland performance in treating occasional organic loads. Field drainage loads had a discontinuous time pattern and occurred mostly during autumn-winter, with the exception of the 2001-2002 season which was a very dry. The wetland discharged 206 kg ha(-1) of N, over the 5-year period, with an apparent removal efficiency of about 90%. The disappearance was mostly due to plant uptake (1110 kg ha(-1)) and soil accumulation (570 kg ha(-1)), with the contribution of denitrification being estimated at around 7%. PMID- 17270251 TI - Population level effects of intersexuality in the marine environment. AB - Whilst there have been many studies indicating links between anthropogenic contaminants and reproductive abnormalities in wildlife, very few studies have addressed the effects that might be occurring at the population level. In this study we aimed to assess the mid and long-term population effects of different levels of intersexuality in an amphipod species, Echinogammarus marinus. This aim was achieved by modelling the dynamics of a population of E. marinus with possible contaminant or parasite induced intersexuality over a ten-year period. The model considers five population groups: juveniles, males, immature females, adult normal females and adult intersex females. The costs associated with intersexuality in E. marinus were incorporated into the model using data from previous studies. The basic run of the model considers a population with 50% normal males and 50% normal females, which are prevalent in some field populations of E. marinus. Results of increasing proportions of intersex females were compared with the basic run and suggest that if intersex females occur at the expense of normal females, the population collapses after approximately 6 and 2.3 years when intersex females account for 5 and 10% of the population, respectively. Conversely, the population density increases exponentially if intersex females occur at the expense of males. However, if the number of intersex females reaches approximately (1/2) of the number of normal females, even if the percent of males in the population is as low as 27% (e.g. 27% males, 45% normal females, 28% intersex females), the population will be extinguished within 10 years. These results suggest a selective advantage in female-biased sex ratios in populations with significant levels of intersexuality, up to a certain threshold, where the increase in the total number of females seems to compensate the lower recruitment rates of intersex individuals, namely, intersex females. Furthermore, even in this scenario, if the recruitment rate of normal females is negatively affected, the population survivorship may be compromised. Modelling the effects of intersexuality in this manner should aid both environmental toxicologists and ecologists in predicting the population level effects of endocrine disrupting chemicals and/or parasites. PMID- 17270252 TI - Synthesizing bioaccumulation data from the German metals in mosses surveys and relating them to ecoregions. AB - The European Heavy Metals in Mosses Surveys measure and map environmental concentrations of metals at more than 7000 sites in Europe. In Germany, moss samples were taken at 592 sites in 1990, at 1026 sites in 1995, and at 1028 sites in 2000, where up to 40 metals were measured each time. This article is about how to calculate multi-metal indices from the site- and metal-specific monitoring data and how to link them with the natural regions (ecoregions) of Germany. The ecoregions were calculated with surface data on natural vegetation, elevation, soil texture and climate by means of Classification and Regression Trees (CART). The ecoregions were mapped by GIS and superimposed on a map of multi-metal bioaccumulation indices calculated by means of geostatistics and percentile statistics from the monitoring data. These indices integrate the concentrations of 8 metals measured in 1990, 1995, and 2000 or 12 metals from the 1995 and 2000 surveys, respectively, and the ecoregionalisation enables their geostatistical estimates to be grouped into 21 ecological land categories. This two-step aggregation revealed that, from 1990 to 2000, the multi-metal metal accumulation declined up to 80%, varying with the ecoregions. Based on the multi-metal accumulation index hot spots, the metal accumulation was mapped, ecoregionalised, and suggested for further ecotoxicological assessment. Thus, the approach helps to assess the metal bioaccumulation within ecoregions in a comprehensive and holistic manner over time, space, and metals. This data aggregation is of importance for the environmental reporting in Germany and within the framework of the international environmental information systems. Furthermore, ecoregions may help to plan and optimize monitoring networks. Because monitoring should measure and estimate not only the environmental concentrations of substances but also their impacts on ecoregions, the number of monitoring sites should be proportional to the areas covered by the ecoregions and located according to their spatial variation. PMID- 17270253 TI - Beyond low-level activity: on a "non-radioactive" gas mantle. AB - Gas mantles for camping gas lanterns sometimes contain thorium compounds. During the last years, the use of thorium-free gas mantles has become more and more popular due to the avoidance of a radioactive heavy metal. We investigated a gas mantle type that is declared to be "non-radioactive" and that can be bought in Austria at the moment. Methods used were Instrumental Neutron Activation Analysis (INAA), gamma-spectroscopy, and Liquid Scintillation Counting (LSC). We found massive thorium contents of up to 259 mg per gas mantle. Leaching experiments showed that only 0.4% of the Th but approximately 90% of the decay products of (232)Th can be leached under conditions simulating sucking and chewing with human saliva. In this paper, the investigation of these gas mantles including the consideration of the environmental hazard caused by disposed mantles and the health hazard for unsuspecting consumers is presented and legal consequences are discussed for this fraud. PMID- 17270254 TI - Lidar observations of the diurnal variations in the depth of urban mixing layer: a case study on the air quality deterioration in Taipei, Taiwan. AB - An aerosol light detection and ranging (LIDAR) system was used to measure the depth of the atmospheric mixing layer over Taipei, Taiwan in the spring of 2005. This paper presents the variations of the mixing height and the mixing ratios of air pollutants during an episode of air quality deterioration (March 7-10, 2005), when Taipei was under an anti-cyclonic outflow of a traveling high-pressure system. It was found that, during those days, the urban mixing height reached its daily maximum of 1.0-1.5 km around noon and declined to 0.3-0.5 km around 18:00 (LST). In terms of hourly averages, the mixing height increased with the ambient temperature linearly by a slope of 166 m/degrees C in daytime. The consistency between the changes in the mixing height and in the ambient temperature implied that the mixing layer dynamics were dominated by solar thermal forcing. As the cap of the mixing layer descended substantially in the afternoon, reduced dispersion in the shallow mixing layer caused the concentrations of primary air pollutants to increase sharply. Consequently, the pollutant concentration exhibited an anti-correlation with the mixing height. While attentions are usually focused on the pollution problems occurring in a morning inversion layer, the results of this study indicate that the air pollution and its health impacts could be even more severe as the mixing layer is getting shallow in the afternoon. PMID- 17270255 TI - Insight into the profibrinolytic activity of dermatan sulfate: effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators. AB - INTRODUCTION: Dermatan sulfate (DS) is well-known for its anticoagulant activity through binding to heparin cofactor II to enhance antithrombin action. It has also been suggested that DS has a profibrinolytic effect, although the exact molecular mechanism is as yet unknown. MATERIALS AND METHODS: An in vitro amidolytic method was used to study the effect of high and low molecular weight DS on the activation of Glu and Lys-plasminogen by tissue and urinary plasminogen activators (t-PA and u-PA). RESULTS: Both high and low molecular weight-DS exhibited a stimulating effect on the activation of plasminogen by PAs. Interestingly, high molecular weight-DS stimulated Glu and Lys-plasminogen activation by t-PA and u-PA in a way and to an extent similar to that in which fibrin(ogen) degradation products (PDF) increased the t-PA assay. Meanwhile low molecular weight-DS had a lower effect. No DS had any effect on plasmin or u-PA amidolytic activity. The facilitation of the conversion of Glu-plasminogen to plasmin in the presence of DS was confirmed by SDS-PAGE; high molecular weight-DS effect was greater than low molecular weight-DS in accordance with the chromogenic assays. Moreover, the combination of PDF and high and low molecular weight-DS, respectively, did not further stimulate t-PA activation of either Glu or Lys-plasminogen suggesting that both substances may compete for the same binding sites. CONCLUSIONS: Through in vitro assays we demonstrated that high and low molecular weight-DS enhance plasminogen activation by u-PA and t-PA, suggesting that the profibrinolytic activity of DS might be via potentiation of plasminogen conversion to plasmin. PMID- 17270257 TI - Locomotor activity to nicotine and Fos immunoreactivity in the paraventricular nucleus of the hypothalamus in adolescent socially-stressed rats. AB - We reported previously that social stressors in adolescence (SS: one-hour isolation and new cage partners daily for 16 days) increased locomotor activity to nicotine and to amphetamine in females, but not in males, when tested as adults. Here, we investigated whether effects of stressors in adolescence on locomotor responses to nicotine would be observed in both sexes if tested closer in time to the stressor exposure. We also tested whether social instability was necessary to alter nicotine's effects on locomotor activity by including a group that underwent daily isolation but was housed with the same partner (ISO). The locomotor-activating effects of nicotine were lower in SS rats compared to ISO and non-stressed control rats. In males, but not in females, there were effects of nicotine treatment and of stress condition on Fos immunoreactive (Fos-ir) cell counts in the paraventricular nucleus (PVN) of the hypothalamus: SS males had higher Fos-ir counts than did ISO and non-stressed control males, and higher Fos ir counts in the PVN were found in repeated-nicotine groups than in acute nicotine and saline groups. These results add to evidence that adolescents are uniquely vulnerable to stressors due to ongoing brain development, and also indicate that effects are sex- and stressor-specific. PMID- 17270256 TI - Sex differences in nicotine levels following repeated intravenous injection in rats are attenuated by gonadectomy. AB - Previous research demonstrates that repeated intravenous (i.v.) nicotine injection resulted in increased locomotor sensitization in female relative to male rats. In order to determine if increased nicotine levels are detected in females compared to males the present experiment examined the plasma nicotine levels of male, female, castrated (CAST), and ovariectomized (OVX) rats (n=7-11 rats/group) following repeated i.v. nicotine injection (50 microg/kg/injection). All rats received 14 i.v. nicotine injections, one/day. Approximately 1 min after the 14th nicotine injection, rats were rapidly decapitated and trunk blood was collected immediately. Gas chromatography revealed a sex difference in nicotine content: higher plasma nicotine levels were measured from female rats (>10 x increase) relative to males, and the sex difference was attenuated by gonadectomy. These data suggest that the sex difference in plasma nicotine levels is due to alteration in distribution or nicotine metabolism as a function of circulating gonadal hormones. These findings indicate that gonadal hormones may influence nicotine pharmacokinetics and therefore nicotine-induced sex differences in behavior. PMID- 17270258 TI - Environmental and immune stressors enhance alcohol-induced motor ataxia in rat. AB - Infection is now accepted as a stressor, consequently we sought to compare the short- and longer-term consequences of several environmental stressors versus an endotoxin challenge on alcohol-induced motor ataxia. The present set of studies examined the impact of intermittent electric shock (SHOCK), intermittent cold water swim (ICWS), or lipopolysaccharide (LPS) administration on the motor ataxic effects of an intraperitoneal (i.p.) injection of alcohol (ETOH). In Experiment 1 SHOCK, but not ICWS, enhanced the motor ataxic effects of ethanol at both 2 and 24 h post-stress. In Experiment 2 administration of LPS did not affect the motor ataxic effects of ETOH 4 h later, but enhanced the ataxic potency of ETOH 24 h later. The results indicate that certain environmental and immune stressors have the potential to alter the long-term behavioral reactivity to alcohol. These examples of stress-induced enhancement of the motor ataxic effects of ETOH may have important implications for the development of alcohol dependence. PMID- 17270259 TI - Advances in pediatric asthma 2006. AB - Because the outcomes experienced in adult asthma often result from pathophysiology that begins in early childhood, this year's summary focuses on recent advances in pediatric asthma. This past year, we have learned that early intervention with inhaled corticosteroids in childhood asthma reduces morbidity but does not alter the natural history of asthma. Theme issues over the last year focused attention on severe asthma and black box warnings. Both of these themes significantly affect the management of childhood asthma. Responsiveness to asthma treatment is heterogeneous even among patients with asthma of similar severity. This heterogeneity calls attention to the importance of assessing control and adjusting treatment accordingly. We are now moving toward an individualized approach to asthma therapy and searching for biomarkers and genetics as a resource to guide treatment. To improve asthma control, we must continue to obtain information on early asthma, severe asthma, asthma exacerbations, and methods to improve asthma control. Evaluation and management of severe asthma in children include verification of the diagnosis, assessment for coexisting illnesses, and identification of effective treatment strategies directed to adherence, medication delivery, and combination therapy. Application of biomarkers and genetics could be useful tools in individualizing our approach to the management of childhood asthma. PMID- 17270260 TI - Cat and dust mite allergen levels, specific IgG and IgG4, and respiratory symptoms in adults. AB - BACKGROUND: Exposure to allergen may induce a modified T(H)2 response characterized by high IgG(4) levels, absence of IgE sensitization, and a decreased risk of allergic respiratory symptoms. OBJECTIVE: To assess the association of IgG(4) level with allergic respiratory symptoms in a community based sample of adults. METHODS: Information on exposure to cats, respiratory symptoms, and mattress allergen levels was obtained from 2780 adults. Levels of cat and house dust mite (HDM) specific IgE, IgG, and IgG(4) were measured. The association of exposure to allergen with IgG(4) and of IgG(4) with symptoms was assessed. RESULTS: Geometric mean (GM) cat specific IgG and IgG(4) was higher in subjects who had a cat that was allowed in the bedroom than in subjects without a cat (adjusted ratio of GM IgG(4), 1.41; 95% CI, 1.25-1.57). Levels of HDM specific IgG and IgG(4) were similar in subjects with undetectable and high (>20.22 microg/g) mattress Der 1 levels (adjusted ratio of GM IgG(4), 1.02; 95% CI, 0.89-1.17). There was no evidence that high cat or HDM specific IgG(4) levels were associated with less IgE sensitization or with fewer symptoms. CONCLUSION: In this community-based sample of adults, high IgG(4) levels to cat or HDM were not associated with a lower risk of allergic respiratory symptoms. CLINICAL IMPLICATIONS: In adults, high cat allergen exposure does not protect against respiratory symptoms. PMID- 17270262 TI - Advances in adult asthma 2006: its risk factors, course, and management. AB - This Advances article updates our understanding of risk factors for asthma and its course and management. Studies relevant to clinical practice are discussed, with special attention to their clinical research methods. PMID- 17270263 TI - The neutrophil in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous collection of conditions characterized by irreversible expiratory airflow limitation. The disease involves a multifaceted progressive inflammatory process leading to the development of mucus hypersecretion, tissue destruction, and disruption to the normal repair and defense mechanisms. The result is increased resistance to airflow in small conducting airways, change in lung compliance, and the premature collapse of airways during expiration that leads to air trapping. Neutrophils are necessary in healthy lungs; they are an important component of innate immunity, protecting healthy individuals against infection. However, in COPD, they play a role in the destructive processes that characterize the disease. They can be responsible for significant damage when they accumulate at sites of inflammation and are harmful to healthy tissue. In recent years, increased understanding of the role of neutrophils has led to improved knowledge of the pathogenesis of COPD and allowed new avenues of treatment to be investigated. PMID- 17270264 TI - Contamination of probiotic preparations with milk allergens can cause anaphylaxis in children with cow's milk allergy. PMID- 17270265 TI - Sex steroid dynamics during embryogenesis and sexual differentiation in Eurasian perch, Perca fluviatilis. AB - It is widely accepted that sex steroid hormones play an important and a specific role during the process of sex differentiation in fish. In order to describe the role of the three main sex steroid hormones (testosterone--T, 17beta-estradiol- E2 and 11keto-testosterone--11KT) during embryogenesis and sex differentiation in Eurasian perch, Perca fluviatilis, eggs, larvae and juveniles originating from two mixed-sex and two all-female progenies were regularly sampled from fertilization to hatching (D0) and from hatching to day 70 post-hatching (D70). Just after spawning, a significant amount of sex steroids [T (1634.2pgg(-1)), E2 (554.4pgg(-1)) and 11KT (1513.2pgg(-1))] was measured in non-fertilised eggs suggesting a maternal transmission of these steroids. From D2 to D70 post hatching, E2 levels were significantly higher in mixed-sex progenies (median: 725.7pgg(-1)) than in all-female progenies (156.2pgg(-1)) and significantly increased after the onset of the histological differentiation of the gonad in both progenies (D35). Levels of 11KT were significantly higher in mixed-sex (median: 431.5pgg(-1)) than in all-female progenies (below the limit of assay detection) and significantly increased at D35 in all-female progenies (median value: 343.2pgg(-1)). Mean 11KT to E2 ratio was six-fold higher in mixed-sex progenies (1.35) than in all-female progenies (0.24). The data suggest that the 11-oxygenated androgen (11KT) plays a major role in the male differentiation process, and that sex differentiation in Eurasian perch is probably determined by the 11KT to E2 ratio. PMID- 17270266 TI - Comparison of methods to stimulate ovarian follicular growth in cynomolgus and African green monkeys for collection of mature oocytes. AB - The objective was to compare various gonadotropin-based methods to stimulate ovarian follicular growth in female cynomolgus (n=16) and African green monkeys (n=8) for collection of mature oocytes. On the 1st day of menstruation, the monkeys were treated with 3.75 mg leuprorelin acetate (a GnRH agonist). Starting 2-3 weeks later, ovarian follicular growth was stimulated as follows: (a) 25 IU/kg of human FSH (hFSH) in a glycerol solution given once daily for 9 d; (b) 200 IU of eCG given six times during a 9-d interval; (c) 75 IU/kg hFSH in a glycerol solution given three times (72 h intervals) during a 6-d interval. In addition, the monkeys were given 1200 or 4000 IU of hCG 36 h (Methods A and B) or 60 h (Method C) after the last gonadotropin treatment, and oocyte collection was attempted 36-38 h after hCG. Although there were no significant differences among methods in the number of oocytes collected, in cynomolgus monkeys, hFSH (Methods A and C) was better than eCG (Method B; 12 and 10 versus 7 mature oocytes, respectively), whereas in African green monkeys, eCG (Method B) was more effective than hFSH (Method A; 12 versus 7 mature oocytes). Furthermore, in cynomolgus monkeys, Method C was nearly as effective as Method A; using a glycerol solution as a solvent decreased the frequency of hFSH administration from nine to three times. In conclusion, in cynomolgus and African green monkeys, ovarian response depended on the species and on the individual, and in cynomolgus monkeys, hFSH in a glycerol solvent was effective. PMID- 17270267 TI - Fractographic ceramic failure analysis using the replica technique. AB - OBJECTIVES: To demonstrate the effectiveness of in vivo replicas of fractured ceramic surfaces for descriptive fractography as applied to the analysis of clinical failures. METHODS: The fracture surface topography of partially failed veneering ceramic of a Procera Alumina molar and an In-Ceram Zirconia premolar were examined utilizing gold-coated epoxy poured replicas viewed using scanning electron microscopy. The replicas were inspected for fractographic features such as hackle, wake hackle, twist hackle, compression curl and arrest lines for determination of the direction of crack propagation and location of the origin. RESULTS: For both veneering ceramics, replicas provided an excellent reproduction of the fractured surfaces. Fine details including all characteristic fracture features produced by the interaction of the advancing crack with the material's microstructure could be recognized. The observed features are indicators of the local direction of crack propagation and were used to trace the crack's progression back to its initial starting zone (the origin). Drawbacks of replicas such as artifacts (air bubbles) or imperfections resulting from inadequate epoxy pouring were noted but not critical for the overall analysis of the fractured surfaces. SIGNIFICANCE: The replica technique proved to be easy to use and allowed an excellent reproduction of failed ceramic surfaces. It should be applied before attempting to remove any failed part remaining in situ as the fracture surface may be damaged during this procedure. These two case studies are intended as an introduction for the clinical researcher in using qualitative (descriptive) fractography as a tool for understanding fracture processes in brittle restorative materials and, secondarily, to draw conclusions as to possible design inadequacies in failed restorations. PMID- 17270269 TI - Reduced expression of FLIP SHORT in bone marrow of low risk myelodysplastic syndrome. AB - Apoptosis is dysregulated in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukaemia (AML). FLIP (FLICE (FAS-associated death-domain-like IL-1 beta-converting enzyme)-inhibitory protein) has been described as an anti apoptotic protein. Here, we characterize the expression level of FLIP(LONG) and FLIP(SHORT) mRNA in bone marrow aspirates from 61 patients diagnosed with MDS or AML. FLIP(SHORT) mRNA expression was significantly lower in low risk MDS, compared to high risk MDS, according to FAB classification (RA/RARS versus RAEB/RAEBt, P=0.0127) and IPSS (low risk/intermediate-1 versus intermediate 2/high risk, P=0.0345). Furthermore, FLIP(SHORT) mRNA expression was significantly lower in low risk MDS, compared to MDS-AML/AML de novo (P=0.0006), according to FAB classification. FLIP(LONG) expression did not differ between these groups. Increased levels of FLIP(SHORT) in RAEB and AML may be related to apoptosis resistance in these diseases and to MDS progression. PMID- 17270271 TI - PTSD and stress sensitisation: a tale of brain and body Part 1: human studies. AB - Post-traumatic stress disorder (PTSD) is a chronic, debilitating psychiatric disorder that can follow exposure to extreme stressful experiences. It is characterised by hyperarousal and increased startle responses, re-experiencing of the traumatic event, withdrawal or avoidance behaviour and emotional numbing. The focus of this review is on aspects that have received less attention. PTSD develops only in a substantial minority of people exposed to traumatic stress, and possible individual traits that increase vulnerability are discussed. An overview is given of the wide variety of physiological disturbances that accompany PTSD and may contribute to disability, including neuroendocrine, cardiovascular, gastrointestinal and immune function and pain sensitivity. Brain imaging and pharmacological studies have generated some insight into the circuitry that may be involved in the generation of PTSD symptoms. Major limitations of human studies so far are the issue of causality and our lack of understanding of the underlying molecular substrates in the brain, which are easier to address in relevant animal models and will be discussed in a companion paper. PMID- 17270268 TI - Fluorescent resonance energy transfer: A tool for probing molecular cell biomaterial interactions in three dimensions. AB - The current paradigm in designing biomaterials is to optimize material chemical and physical parameters based on correlations between these parameters and downstream biological responses, whether in vitro or in vivo. Extensive developments in molecular design of biomaterials have facilitated identification of several biophysical and biochemical variables (e.g. adhesion peptide density, substrate elastic modulus) as being critical to cell response. However, these empirical observations do not indicate whether different parameters elicit cell responses by modulating redundant variables of the cell-material interface (e.g. number of cell-material bonds, cell-matrix mechanics). Recently, fluorescence resonance energy transfer (FRET) has been applied to quantitatively analyze parameters of the cell-material interface for both two- and three-dimensional adhesion substrates. Tools based on FRET have been utilized to quantify several parameters of the cell-material interface relevant to cell response, including molecular changes in matrix proteins induced by interactions both with surfaces and cells, the number of bonds between integrins and their adhesion ligands, and changes in the crosslink density of hydrogel synthetic extracellular matrix analogs. As such techniques allow both dynamic and 3-D analyses they will be useful to quantitatively relate downstream cellular responses (e.g. gene expression) to the composition of this interface. Such understanding will allow bioengineers to fully exploit the potential of biomaterials engineered on the molecular scale, by optimizing material chemical and physical properties to a measurable set of interfacial parameters known to elicit a predictable response in a specific cell population. This will facilitate the rational design of complex, multi-functional biomaterials used as model systems for studying diseases or for clinical applications. PMID- 17270272 TI - Levels of PCDD/PCDFs and PCBs in edible marine species and human intake: a literature review. AB - Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) are lipophilic organic compounds whose origin comes from many different sources. PCDD/Fs and PCBs are ubiquitous and persistent environmental pollutants with a well known potential toxicity, which were included at the 1998 UN-EC POP protocol. Although human exposure to PCDD/Fs and PCBs can occur by various routes, food is the primary source. A number of studies have shown that the major food sources of these organic pollutants are fat-containing animal products, including fish and other seafood. Because of the frequent health recommendations concerning fish consumption, to determine the contribution to the dietary intake of chemical contaminants such as PCDD/Fs and PCBs through fish and other seafood consumption is an issue of special interest. This paper reviews the state of the science regarding recent literature on PCDD/F and PCB levels in marine species and human intake through fish and seafood consumption. The concentrations of these pollutants depend basically on the environment in which the respective species are caught. It is concluded that some groups of population frequently consuming high quantities of certain species could be significantly increasing health risks due to PCDD/F and PCB exposure. PMID- 17270273 TI - Cytochrome P450-catalyzed pathways in human brain: metabolism meets pharmacology or old drugs with new mechanism of action? AB - The true importance of cytochrome P450 enzymes, not just in drug metabolism but also in pharmacology, is only beginning to be appreciated. Though originally discovered through their role in the biotransformation of xenobiotics, the P450 enzyme super family is ubiquitous in nature and necessarily evolved around endogenous pathways. The extent of tissue- and cell-specific expression of individual P450 isoforms has led many investigators to hypothesize localized roles in endogenous biochemical pathways for isoforms traditionally thought of as drug-metabolizing. In some cases, direct evidence from humanized transgenic animal models can confirm the degree to which such enzymes modulate endogenous pathways. However, overlapping P450 substrate specificities may mask genetic or biochemical deficiencies, such that many of these reactions appear nonessential. Nonetheless, the drug-induced alteration of local biochemical concentrations in extrahepatic tissues due to metabolism by and inhibition of P450 isoforms has tremendous potential for introducing unexpected pharmacological effects. Nowhere is this truer than in the CNS. On the other hand, if we can harness the power of in silico modeling to create highly specific inhibitors of identified brain isoforms, a novel avenue for drug design using P450 as drug targets may be at hand. This article highlights some notable examples in which the catalytic state of specific P450 isoforms involved in endogenous biochemical reaction pathways are influenced by pharmacological agents. The implications of inhibition of P450 catalzyed oxidation steps that are known or speculated to influence arachadonic acid, cholesterol, and catecholamine neurotransmitters pathways in human brain will be considered. PMID- 17270274 TI - Golgi, Cajal, and the fine structure of the nervous system. AB - Towards the middle of the 20th century, neuroanatomy was on the decline. It was revived by the development of two new methods. One was the Nauta-Gygax method, which selectively stained nerve fibers that had been caused to degenerate by experimental lesions. This allowed connections between various parts of the nervous system to be better determined. The second was electron microscopy, which allowed the structure of neurons and the synapses between them to be examined in detail, and eventually this led to a revival of the Golgi impregnation methods. This occurred in the 1970s because of the desire of electron microscopists to determine the origins of the neuronal profiles they encountered in electron micrographs of various parts of the central nervous system. Eventually this led to the development of Golgi/EM techniques, whereby individual impregnated neurons could first be characterized by light microscopy and then thin sectioned for detailed analyses. Examining the axon terminals of such impregnated neurons, especially those in the cerebral cortex, for the first time revealed details of intercellular connections and allowed neuronal circuits to be postulated. However, Golgi/EM had only a brief, but fruitful existence. It was soon superceded by intracellular filling techniques, which allowed the added dimension that the physiological properties of identified neurons could also be determined. PMID- 17270275 TI - Copper deficiency and neurological disorders in man and animals. AB - Copper metabolism in the brain is far from being completely understood and further studies are needed on the role of copper in the CNS, starting with careful measurements, metal and biological speciation of metabolites on the molecular level, and combining copper concentration in different brain areas with morphological as well as biochemical alteration after Cu-depletion/deficiency. So far a pathological role for copper has been clearly demonstrated in some human genetic diseases (e.g., Menkes' and Wilson's diseases), but other pathological features connected with metal depletion are under investigation in several laboratories. The metabolic interaction between copper and other metal ions in some neurological disorders is also discussed in this contribution. PMID- 17270276 TI - Tryptophan breakdown pathway in bipolar mania. AB - The upregulation of the initiating step of the kynurenine pathway was demonstrated in postmortem anterior cingulated cortex from individuals with schizophrenia and bipolar disorder. However, the tryptophan and kynurenine metabolism in bipolar mania patients especially in drug naive state has not been clearly explored. This study explored the plasma tryptophan and its competing amino acids, kynurenine, kynurenic acid and 3-hydroxyanthranillic acid and their association with psychopathological scores in 39 drug naive and drug-free bipolar manic patients in comparison with 80 healthy controls. When age and gender were controlled in multivariate analysis, bipolar manic patients have significantly lower tryptophan index than normal controls (f=9.779, p=0.004). The mean plasma tryptophan concentration and mean tryptophan index were reduced and mean tryptophan breakdown index was increased significantly after a 6-week treatment. The reduction in plasma tryptophan and reduction in tryptophan index showed significant negative correlation with reduction in YMRS score (r=-0.577, p=0.019 and r=-0.520, p=0.039 respectively). The reduction in YMRS also showed positive correlation with both plasma tryptophan concentration and tryptophan index both at the time of admission (r=0.464, p=0.019 and r=0.4, p=0.047 respectively) and discharged (r=0.529, p=0.035 and r=0.607, p=0.013 respectively). The reduction in BPRS score also showed positive correlation with tryptophan index at the time of discharge (r=0.406, p=0.044). These findings indicated the involvement of bi directional tryptophan metabolism and kynurenine pathway in pathophysiology and response to medication in bipolar mania. PMID- 17270277 TI - Origin, localization and binding abilities of boar DQH sperm surface protein tested by specific monoclonal antibodies. AB - Seminal plasma proteins bind the sperm surface at ejaculation and may modulate several aspects of sperm activity during reproduction. DQH sperm surface protein, present in boar seminal plasma, shows affinity to phoshorylcholine, acidic polysaccharides, oviductal epithelium and zona pellucida glycoproteins. Monoclonal antibodies (MAbs) against DQH protein were prepared and used for determination of the DQH protein origin in boar reproductive organs, its localization on boar spermatozoa, and for investigation of its binding abilities in the porcine oviduct and to the zona pellucida of the oocyte. The mRNA transcript of DQH protein was found in seminal vesicles and not in the testis, epididymis and prostate. Its translated products were immunodetected by MAbs in seminal vesicle extract and fluid, in seminal vesicle tissue sections and on the membrane-associated acrosomal part of ejaculated spermatozoa. These results confirm the ability of DQH protein to bind the sperm surface at ejaculation and to participate in formation of the sperm reservoir in the porcine oviduct. Moreover, monoclonal antibodies reduced binding of sperm to oocytes and proved the role of DQH protein in the sperm-zona pellucida primary binding. PMID- 17270278 TI - The five-factor gambling motivation model. AB - Pathological gambling is a serious social issue, but the underlying psychological motivations are poorly understood. This study developed a five-factor gambling motivation model. The five factors that motivate gambling (socialization, amusement, avoidance, excitement, and monetary motives) were derived from study data obtained from 240 college students. The structure of the five-factor model was confirmed by factor analysis of responses from 234 frequent gamblers. We then compared the "monetary motive version" of this model with the "parallel version" to determine which model more accurately describes how the five factors influence gambling. The monetary motive model holds that amusement, excitement, and avoidance motives influence gambling severity only through mediation of the monetary motive. The parallel model proposes that the five motives all independently influence gambling severity. We found that the avoidance and excitement motives did not have direct effects on gambling severity, but the monetary motive showed a direct positive influence. Thus the monetary motive model was more effective than the parallel model in explaining the influence of specific gambling motives on gambling severity. These findings may help in the improvement of therapy for pathological gambling. PMID- 17270279 TI - Self-efficacy and empowerment as outcomes of self-stigmatizing and coping in schizophrenia. AB - The concept of internalized stigma or self-stigma is central to the understanding of the psychological harm caused by stigma. In this study, we aim to demonstrate how the evaluative dimension of self-concept (self-efficacy and empowerment) mediates the psychological effects of self-stigmatizing and coping with stigma. As important examples of psychological effects, depression and quality of life were focussed on. In 172 outpatients with DSM-IV schizophrenia, measures of self stigma and devaluation, coping with stigma, self-efficacy, empowerment, quality of life and depression were assessed. It was hypothesized that withdrawal and secrecy as important coping strategies yielded to higher levels of anticipatory anxiety of future stigmatizing. Higher levels of perceived discrimination and devaluation were hypothesised to undermine self-efficacy and illness-related empowerment. Lowering of empowerment was supposed to enhance depression and reduce quality of life. This hypothesis was tested by Structural Equation Modeling as a method of data analysis. The results supported the hypothesized model; i.e., 46% of depression and 58% of quality of life reduction could be explained by eroded empowerment. Moreover, 51% of the empowerment reduction was explained by reduction in self-efficacy at a more general level by dysfunctional coping and higher levels of anticipated stigma. Taken together, our data suggest an avoidant coping style as a risk factor for anticipatory stigma, which erodes self-efficacy and empowerment. These data have implications for cognitive behavioral approaches, which should focus on anticipated stigma to improve recovery in schizophrenia. PMID- 17270280 TI - Platelet serotonin and serum cholesterol concentrations in suicidal and non suicidal male patients with a first episode of psychosis. AB - Suicidal behavior is a major health risk in psychiatric disorders, especially in schizophrenia, wherein up to 10% patients will commit suicide. However, the neurobiology of suicide is still unclear. Suicidality has been related to decreased central serotonergic (5-hydroxytryptamine, 5-HT) function and reduced cholesterol levels. Platelet 5-HT has been used as a peripheral marker of the central serotonergic synaptosomes. The aim of this study was to evaluate serum cholesterol and platelet 5-HT concentrations in suicidal and non-suicidal men in the first episode of psychosis and in healthy male controls. Venous blood samples were collected within 24 h of admission, and serum cholesterol and platelet 5-HT were determined enzymatically and fluorimetrically. Platelet 5-HT and serum cholesterol concentrations were significantly lower in suicidal than in non suicidal patients in the first episode of psychosis, and also lower than in healthy controls. Our results suggest that lower concentrations of serum cholesterol and platelet 5-HT in patients with a first episode of psychosis might be useful biological markers of suicidality. PMID- 17270281 TI - Cell-mediated immune responses differentiate infections with Brucella suis from Yersinia enterocolitica serotype O:9 in pigs. AB - Due to almost identical lipopolysaccharide (LPS) O-antigens, infections with Yersinia enterocolitica serotype O:9 (YeO:9) cause false positive serological reactions (FPSR) in tests for Brucella and thus cause problems in National Brucella surveillance programs. As LPS are strong inducers of antibody responses it was hypothesized that cell-mediated immune responses to non-LPS antigens of the two bacteria can be used to separate immune responses to these two biologically very different infections. Following subclinical experimental infections with Brucella suis biovar 2, high interferon-gamma (IFN-gamma) assay responses with a commercial Brucella melitensis antigen preparation (Brucellergene OCB) preceded the development of antibodies. High IFN-gamma responses in the seven B. suis inoculated pigs with serological evidence of infection were consistent throughout a 20-week post-inoculation observation period. In contrast, IFN-gamma responses in two B. suis inoculated pigs without bacteriological or serological evidence of infection were below a cut-point of 25pg/ml at all samplings. IFN-gamma responses in repeated samplings from 5 uninfected control pigs and 18 pigs experimentally infected with YeO:9 were all negative, except for solitary false positives in 3.7% of the samples from both the experimentally YeO:9 infected pigs and control pigs. Skin tests using the same commercial Brucella antigen confirmed the ability of cell-mediated immune responses to differentiate between the two infections. In addition, a field evaluation of the diagnostic use of cell-mediated immune responses by IFN-gamma assay and skin test to resolve serological suspicions of Brucella was conducted in an YeO:9 infected pig herd. Following a screening of 200 pigs 39 pigs were identified with false positive serological Brucellosis reactions. While 36 of the 39 FPSR pigs were also FPSR in a second test, none of the pigs were test positive in whole blood IFN-gamma assay or Brucellergene OCB skin test. In conclusion, use of IFN-gamma assay and skin test as measurements of cell-mediated immune responses to non-LPS Brucella antigens were specific and sensitive in discriminating subclinical experimental infections with B. suis from both natural and experimental infections with YeO:9. PMID- 17270282 TI - CpG DNA inhibits CD4+CD25+ Treg suppression through direct MyD88-dependent costimulation of effector CD4+ T cells. AB - Toll-like receptor (TLR) ligands are notable for their ability to induce APC maturation, which in turn facilitates optimal T cell mediated immune responses. Toll-like receptor ligands, such as CpG DNA, can also modulate immune responses by blocking the suppressive effects of CD4+CD25+ regulatory T cells (Tregs). Recently, we have demonstrated that CpG DNA, in addition to its actions on APCs and Tregs, can provide direct costimulatory signals to CD4+CD25- T cells. Here we show that this costimulatory effect is sufficient to abrogate suppression by Tregs. These data indicate a previously undefined role for TLR ligands in directly modulating CD4+ T cell responses. PMID- 17270283 TI - HDAC inhibitors TSA and sodium butyrate enhanced the human IL-5 expression by altering histone acetylation status at its promoter region. AB - The expression of IL-5 correlated tightly with the maturation and differentiation of eosinophils, and is considered as a cytokine responsible for allergic inflammation. We report here that inhibition of HDAC activity by Trichostatin A (TSA) and sodium butyrate (NaBu), the two specific HDAC inhibitors, resulted in the elevation of both endogenous and exogenous activity of IL-5 promoter. We demonstrated that both the mRNA expression and protein production of IL-5 were stimulated by TSA and NaBu treatments. ChIP assays showed that treatments of TSA and NaBu caused hyperacetylation of histones H3 and H4 on IL-5 promoter in Jurkat cells, which consequently promoted the exogenous luciferase activity driven by this promoter. Moreover, site-directed mutagenesis studies showed that the binding sites for transcription factors NFAT, GATA3 and YY1 on IL-5 promoter were critical for the effects of TSA and NaBu, suggesting that the transcriptional activation of IL-5 gene by these inhibitors was achieved by affecting HDAC function on IL-5 promoter via transcription factors. These data will contribute to elucidating the unique mechanism of IL-5 transcriptional control and to the therapy of allergic disorders related to IL-5. PMID- 17270284 TI - Comment on "Measuring health-related quality of life after pediatric cochlear implantation: A systematic review" by Lin and Niparko [Int. J. Pediatr. Otorhinolaryngol. 70 (2006) 1695-1706]. PMID- 17270285 TI - Effects of valproic acid on hearing in epileptic patients. AB - OBJECTIVE: Since some case reports about the ototoxicity of valproic acid have been published, probable adverse effects of valproic acid on hearing in the epileptic patients became a subject of interest. We wanted to investigate if ototoxicity occurs in pediatric epileptic patients using VPA for long terms. METHODS: Twenty-one epileptic patients who have been using valproic acid at least for 6 months as monotherapy and 21 age-sex matched controls were included in the study. Audiometric tests were performed to all patients between the frequencies of 125 and 16,000 Hz. The effects of dosage, duration of therapy and serum levels of the VPA, on the audiometric results were investigated and the audiometric results were compared between the groups. RESULTS: There was no difference in hearing thresholds of the groups between 125 and 16,000 Hz frequencies. Relation could not be established between the duration of VPA therapy, dosage of the drug, blood level of drug, age and sex of the patients and the auditory signs. CONCLUSIONS: Although we could not find any deleterious effect of VPA on hearing thresholds in our patient series, we think it is useful to perform audiometric tests at intervals while VPA is being used for long periods, considering the presented case reports about sensorineural hearing loss. PMID- 17270287 TI - Xenin reduces feed intake by activating the ventromedial hypothalamus and influences gastrointestinal transit rate in chicks. AB - This study was conducted to determine the effects of xenin on appetite related processes in chicks. Chicks were centrally and peripherally administered xenin, and feed and water intake were quantified. Chicks responded with a linear dose dependent decrease in feed intake to central xenin and had a quadratic type response to peripheral administration. Water intake was not affected by treatment. To determine if the lateral hypothalamus (LH) or ventromedial hypothalamus (VMH) was involved in this effect, chicks were both centrally and peripherally injected with xenin and an immunocytochemistry assay for c-Fos was conducted. Central and peripheral xenin caused increased activation of the VMH but had no effect on the LH. Finally, to determine if gastrointestinal transit rate was affected, chicks received central xenin and were gavaged with chicken feed slurry containing a visible marker. Chicks exhibited a quadratic dose dependent response to transit rate after central xenin. These results suggest that xenin affects feeding and gastrointestinal motility through hypothalamic interactions in chicks. PMID- 17270288 TI - Exploratory activity, motor coordination, and spatial learning in Mchr1 knockout mice. AB - Male mice with a null mutation of Mchr1, encoding melanin concentrating hormone receptor-1, were compared to wild-type on two background strains. Mchr1 knockout (KO) mice were more active than 129/SvEv and C57BL/6J wild-type strains in a photocell actimeter. In addition, Mchr1 KO mice on the C57BL/6J background were less anxious in the elevated plus-maze, while on the 129/SvEv background, the mutants were less emotionally reactive as estimated by fecal boli and handling related vocalization. There was no detrimental impact of the null mutation on motor coordination and spatial learning. Mchr1 KO mice had shorter latencies before reaching the escape platform, but only on the 129/SvEv background. Null mutants were lighter than C57BL/6J controls but heavier than 129/SvEv controls, attributable to interactions with strain-dependent genes. PMID- 17270289 TI - Characterization of a Trypanosoma cruzi acetyltransferase: cellular location, activity and structure. AB - Trypanosomatids are widespread parasites that cause three major tropical diseases. In trypanosomatids, as in most other organisms, acetylation is a common protein modification that is important in multiple, diverse processes. This paper describes a new member of the Trypanosoma cruzi acetyltransferase family. The gene is single copy and orthologs are also present in the other two sequenced trypanosomatids, Trypanosoma brucei and Leishmania major. This protein (TcAT-1) has the essential motifs present in members of the GCN5-related acetyltransferase (GNAT) family, as well as an additional motif also found in some enzymes from plant and animal species. The protein is evolutionarily more closely related to this group of enzymes than to histone acetyltransferases. The native protein has a cytosolic cellular location and is present in all three life-cycle stages of the parasite. The recombinant protein was shown to have autoacetylation enzymatic activity. PMID- 17270290 TI - Characterization and localization of Plasmodium falciparum homolog of prokaryotic ClpQ/HslV protease. AB - The beta subunits (beta1, beta2, and beta5) of 20S proteasome and HslV/ClpQ are ATP-dependent threonine proteases present in eukaryotes and prokaryotes, respectively that control levels of key regulatory proteins in the cell. The orthologue of prokaryotic HslV protease in Plasmodium falciparum (PfHslV) is a novel drug target candidate that has no homolog in the human host. In the present study, the PfHslV was expressed, localized and biochemically characterized. The recombinant PfHslV harbored threonine protease specific activity as well as chymotrypsin like and peptidyl glutamyl peptide hydrolase activities. All the three activities could be inhibited by respective specific inhibitors. The protein was localized in the cytosol of the parasite as a soluble protein by Western immunoblotting of parasite fractions and by immuno-fluorescence microscopy. Activity of the protease in the parasite was ascertained by following the degradation of GFP in a transgenic parasite line expressing fusion protein of GFP and Arc-repressor gene, a known target of HslV protease in the prokaryotes. A model structure of PfHslV was constructed based on the crystal structure of Escherichia coli HslV to assess the structural homology. Availability of the structure model of PfHslV may facilitate identification or designing of novel and specific drugs against PfHslV. The in vitro protease assays with recombinant PfHslV and the transgenic parasite line generated in the present study may be exploited in the screening of novel inhibitors to evaluate their anti-malarial activity. PMID- 17270291 TI - RCAN3, a novel calcineurin inhibitor that down-regulates NFAT-dependent cytokine gene expression. AB - The regulators of calcineurin (RCAN) proteins, previously known as calcipressins, have been considered to be a well conserved family from yeast to human based on the conservation of their FLISPP motif. Here, after performing a RCAN comparative genomic analysis we propose the existence of a novel functionally closely related RCAN subfamily restricted to vertebrates, the other RCAN proteins being considered only as distantly related members of the family. In addition, while three paralogous RCAN genes are found in vertebrates, there is only one in the other members of Eukarya. Moreover, besides the FLISPP motif, these paralogous genes have two others conserved motifs, the Cn-inhibitor RCAN (CIC) and the PxIxxT, which are restricted to vertebrates. In humans, RCAN1 and RCAN2 bind and inhibit Cn through their C-terminal region. Given the high amino acid identity in this region among human RCANs, authors in the field have hypothesized a role for RCAN3 in inhibiting Cn activity. Here, we demonstrate for the first time that human RCAN3, encoded by the RCAN3 (also known as DSCR1L2) gene, interacts physically and functionally with Cn. This interaction takes place only through the RCAN3 CIC motif. Overexpression of this sequence inhibits Cn activity towards the nuclear factor of activated T cells (NFAT) transcription factors and down regulates NFAT-dependent cytokine gene expression in activated human Jurkat T cells. PMID- 17270293 TI - Instability mechanisms in unstable angina according to baseline serum levels of C reactive protein: the role of thrombosis, fibrinolysis and atherosclerotic burden. AB - BACKGROUND: Mechanisms of instability in patients affected by unstable angina and who exhibit low levels of C-reactive protein (CRP) on admission are unclear. We compared levels of markers of thrombin generation [thrombin-antithrombin complexes (TAT), of fibrinolysis [plasmin-antiplasmin complexes (PAP)], and angiographic severity and extent of coronary atherosclerosis in patients with severe unstable angina and high or low systemic levels of CRP. METHODS: Forty consecutive patients (age 59.7+/-8.7, 76% males) admitted to our coronary care unit with severe unstable angina (Braunwald class IIIB) were included in the present study. We assayed TAT and PAP using commercially available ELISA assays and CRP with high sensitivity nephelometry. The evaluation of atherosclerotic disease severity and extent was performed. Patients were divided in two groups according to CRP levels: G1=CRP>3 mg/L and G2=CRP<3 mg/L. RESULTS: Number of diseased vessels and number of stenoses plus occlusion were similar between the two groups (1.8+/-0.9 in G1 vs 2.2+/-0.9 in G2, p=NS and 2.6+/-1.9 in G1 vs 2.7+/ 1.3 in G2, p=NS, respectively), as well as extent score and index (8.4+/-4.5 in G1 vs 9.2+/-3.1 in G2, p=NS and 0.6+/-0.3 in G1 vs 0.6+/-0.27 in G2, p=NS, respectively). Episodic activation of thrombin generation, as assessed by TAT was more frequent in G1 than in G2 (85% vs 47%, p=0.03). Episodic activation of the fibrinolysis was more frequent in G1 than in G2 (80% vs 40%, p=0.01). CONCLUSION: Patients with coronary instability and systemic evidence of inflammation exhibit more frequent activation of the thrombin/fibrinolysis system than patients with a similar clinical presentation but no evidence of systemic inflammation, whereas the coronary atherosclerotic burden is similar. The mechanisms of coronary instability in the absence of systemic evidence of inflammation need to be elucidated by future studies. PMID- 17270292 TI - TGFbeta1 regulation of vimentin gene expression during differentiation of the C2C12 skeletal myogenic cell line requires Smads, AP-1 and Sp1 family members. AB - Vimentin exhibits a complex pattern of developmental and tissue-specific expression regulated by such growth factors as TGFbeta1, PDGF, FGF, EGF and cytokines. Vimentin is expressed in the more migratory, mesenchymal cell and its expression is often down-regulated to make way for tissue-specific intermediate filaments proteins such as desmin in muscle. Here, we suggest a mechanism to explain how TGFbeta1 contributes to the up-regulation of vimentin expression while blocking myogenesis. TGFbeta1 binds to serine/threonine kinase receptors resulting in the phosphorylation of Smad2 and Smad3, followed by formation of a heteromeric complex with Smad4. The translocation of this complex to the nucleus modulates transcription of selected genes such as vimentin. However, the vimentin gene lacks a consensus TGFbeta1 response element. By transient transfection analysis of vimentin's various promoter elements fused to the CAT reporter gene, we have determined that tandem AP-1 sites surrounded by GC-boxes are required for TGFbeta1 induction. Mutations within this region eliminated the ability of Smad3 to induce reporter gene expression. DNA precipitation and ChIP assays suggest that c-Jun, c-Fos, Smad3 and Sp1/Sp3 interact over this region, but this interaction changes during myogenesis with TGFbeta1 induction. PMID- 17270295 TI - Nuclear factor-kappaB activity in peripheral blood mononuclear cells in cachectic and non-cachectic patients with chronic heart failure. AB - BACKGROUND: Inflammatory immune mechanisms are involved in the pathogenesis and progression of chronic heart failure (CHF), and also promote the development of generalised body wasting seen in this syndrome. We examined the activity of nuclear factor kappa-B (NF-kappaB), the major mediator of immune response, in peripheral blood mononuclear cells (PBMC) isolated from cachectic and non cachectic patients with CHF. METHODS: Using electromobility shift assay, NF kappaB activity was assessed in nuclear fractions of PBMC isolated from 43 patients with systolic CHF (88% men, age: 64 years [median], left ventricular ejection fraction [LVEF]: 30%, ischaemic CHF aetiology: 79%, NYHA class [I/II/III/IV]: 2/21/19/1, 10 patients with cardiac cachexia) and 12 healthy adult subjects. RESULTS: As compared to healthy controls, NF-kappaB activity in PBMC was increased in patients with CHF (P<0.05), in particular in those with severe CHF (NYHA class III-IV) (P<0.05). NF-kappaB activity in PBMC in CHF patients was not related either to age, sex, CHF aetiology, LVEF, or any clinical parameters reflecting disease severity (haemoglobin, LDL cholesterol, sodium and creatinine levels) (all P>0.1). Regardless of the severity of CHF expressed as NYHA class, patients with cardiac cachexia demonstrated significantly reduced NF-kappaB activity in PBMC as compared to both non-cachectic CHF patients (P<0.001) and healthy controls (P<0.05). CONCLUSION: The activity of NF-kappaB system in peripheral immune cells is augmented in patients with advanced CHF, whereas it is diminished in those with cardiac cachexia. The significance of derangements within NF-kappaB system in PBMC for immune phenomena seen in cachectic and non cachectic CHF patients remains further studies. PMID- 17270294 TI - Influence on aerobic fitness on aortic stiffness in apparently healthy Caucasian and African-American subjects. AB - BACKGROUND: Previous research suggests that arterial stiffness may be significantly higher in African-Americans compared to Caucasians. However, the influence of aerobic fitness on the putative difference in arterial stiffness between these groups has not been previously investigated. METHODS: Two hundred forty-eight subjects (215 Caucasian, 33 African-American) participated in this study. Within one week following enrollment, subjects underwent body mass index (BMI, kg/m2) assessment, cardiopulmonary exercise testing and measurement of aortic wave velocity (AWV, m/s) via magnetic resonance imaging. Initially, 33 Caucasian subjects were randomly age (+/-4 years) and sex-matched (10 male/23 female) to the African-American subjects. 25 Caucasian subjects were then randomly matched for age (+/-4 years), sex (7 male/18 female) and maximal oxygen consumption (VO2Max+/-7 mlO2 kg(-1) min(-1)) to the African-American subjects. Matching based upon VO2Max criteria was not possible for 8 African-American subjects. RESULTS: In the age and sex-matched analysis, Caucasian subjects demonstrated a significantly higher VO2Max (38.3+/-9.6 vs. 27.9+/-8.6 mlO2 kg(-1) min(-1), p<0.001) and lower BMI (24.5+/-3.2 vs. 29.3+/-6.2 kg/m2, p<0.001) and AWV (5.8+/-1.7 vs. 6.7+/-1.5 m/s, p=0.03). However, when subjects were matched for age, sex and VO2Max, the differences in both BMI (26.8+/-5.5 vs. 27.9+/-5.6 kg/m2, p=0.45) and AWV (6.1+/-1.8 vs. 6.5+/-1.6 m/s, p=0.77) were insignificant. CONCLUSIONS: The results of the present study suggest that previously reported differences in arterial stiffness between Caucasians and African-Americans are at least partially a consequence of a lower level of aerobic fitness in the latter group, a phenomenon that has also been previously demonstrated. PMID- 17270296 TI - Effects of perindopril on long-term clinical outcome of patients with coronary artery disease and preserved left ventricular function. AB - BACKGROUND: The EUROPA trial has demonstrated that an ACE inhibitor perindopril, was able to significantly decrease the risk of major cardiac events in patients with stable coronary heart disease without apparent heart failure. AIM: To assess the long-term clinical outcome of patients with stable coronary heart disease and preserved left ventricular function (left ventricular ejection fraction (LVEF> or =40%). METHODS: A retrospective evaluation of LVEF was performed in the EUROPA study population. Among the 12,218 patients of EUROPA, we identified 7096 (58%) patients who had LVEF measurement before randomization. The measurements were obtained mainly by echocardiography in 5214 cases (73%) or by angiography in 1470 cases (21%). Two groups of patients were studied: 6878 (97 %) patients with LVEF> or =40% (3429 received 8 mg of perindopril and 3449 received a placebo) and 218 patients (3%) with a LVEF<40% (111 received perindopril and 107 a placebo). RESULTS: The baseline characteristics of patients with documented LVEF were similar to the whole EUROPA population in terms of demographics, medical history, physical examination (heart rate, blood pressure), and medications at screening. The mean LVEF of this population was 57.0+/-10.4%. In patients (n=6878) with preserved LV function (LVEF> or =40%), there was a significant relative risk reduction of 16% of the primary endpoint (a composite of cardiovascular death, non-fatal myocardial infarction and resuscitated cardiac arrest) in the group treated with perindopril (8.3%) in comparison to the group treated with placebo (9.8%): Hazard ratio (HR)=0.84 [95% CI: 0.72-0.99] p=0.033). Similar results were obtained for the first secondary endpoint (total mortality, non-fatal myocardial infarction, hospital admission for unstable angina and cardiac arrest with successful resuscitation): HR=0.85 [95% CI: 0.76-0.96] p=0.008, for cardiovascular mortality and non-fatal MI: HR=0.84 [95% CI: 0.72-0.99] p=0.036. Similar benefits were observed in patients with an LVEF> or =40% and a history of previous myocardial infarction and in patients with an LVEF<40%. CONCLUSIONS: LVEF was documented in 58% of the EUROPA study population and only 3% had an impaired LV function, confirming that EUROPA patients did not have asymptomatic LV dysfunction. Results in patients with preserved LV function are consistent with those of the whole EUROPA study population and perindopril 8 mg is beneficial in the broad spectrum of patients with stable coronary artery disease without evidence of heart failure. PMID- 17270297 TI - Elevated high sensitivity CRP levels in patients with mitral stenosis and left atrial thrombus. AB - Stasis of blood in the left atrium (LA) due to mitral obstruction is the principal mechanism of LA thrombus formation in patients with mitral stenosis (MS). The purpose of this case-control study was to determine the additional contributions of abnormal homosysteine/folate/B12 levels, chronic inflammation and markers of a procoagulant state. We found that elevated hsCRP levels were associated with the presence of left atrial thrombus, independent of the influence of conventional parameters indicating the severity of MS and its consequences. PMID- 17270298 TI - Modeling the relationship between food animal health and human foodborne illness. AB - To achieve further reductions in foodborne illness levels in humans, effective pre-harvest interventions are needed. The health status of food animals that are destined to enter the human food supply chain may be an important, although often overlooked, factor in predicting the risk of human foodborne infections. The health status of food animals can potentially influence foodborne pathogen levels in three ways. First, diseased animals may shed higher levels of foodborne pathogens. Second, animals that require further handling in the processing plant to remove affected parts may lead to increased microbial contamination and cross contamination. Finally, certain animal illnesses may lead to a higher probability of mistakes in the processing plant, such as gastrointestinal ruptures, which would lead to increased microbial contamination and cross-contamination. Consequently, interventions that reduce the incidence of food animal illnesses might also help reduce bacterial contamination on meat, thereby reducing human illness. Some of these interventions, however, might also present a risk to human health. For example, the use of antibiotics in food animals can reduce rates of animal illness but can also select for antibiotic-resistant bacteria which can threaten human treatment options. In this study, we present a mathematical model to evaluate human health risks from foodborne pathogens associated with changes in animal illness. The model is designed so that potential human health risks and benefits from interventions such as the continued use of antibiotics in animal agriculture can be evaluated simultaneously. We applied the model to a hypothetical example of Campylobacter from chicken. In general, the model suggests that very minor perturbations in microbial loads on meat products could have relatively large impacts on human health, and consequently, small improvements in food animal health might result in significant reductions in human illness. PMID- 17270300 TI - Metabotropic glutamate receptor subtype-1 is essential for motor coordination in the adult cerebellum. AB - We previously demonstrated that metabotropic glutamate receptor-subtype 1 knockout [mGluR1 (-/-)] mice showed ataxic gait, deficient long-term depression and impaired synapse elimination and these phenotypes were rescued by introduction of an mGluR1 transgene with Purkinje cell-specific promoter (mGluR1 rescue mice). However, roles of mGluR1 in the adult brain remain elusive, mainly due to lack of conventional and reproducible method to block mGluR1 expression at a certain developmental stage. Here, we established a versatile mouse line, mGluR1 conditional knockout (cKO) mice using the tetracycline-controlled gene expression system to understand the roles of mGluR1 in the adult brain. The mGluR1 cKO mice express mGluR1 only in Purkinje cells and show normal motor coordination. Blockade of expression of mGluR1 in the adult mGluR1 cKO mice led to impaired motor coordination, suggesting that mGluR1 is essential for cerebellar function in mice not only during postnatal development but also in adulthood. PMID- 17270301 TI - Evaluation of direct plating methods to enumerate Alicyclobacillus in beverages. AB - Ten agar media were evaluated for their suitability to support spore germination and colony development by six strains of Alicyclobacillus acidoterrestris, three strains of Alicyclobacillus acidocaldarius, and one strain of Alicyclobacillus cycloheptanicus. The influence of plating method (pour versus spread), incubation temperature (43 degrees C and 50 degrees C), and incubation time (up to 10 days) on colony development were determined. K agar, Alicyclobacillus medium (ALI agar), and Bacillus acidoterrestris thermophilic (BAT) agar recovered the highest numbers of spores. Orange serum agar and Hiraishi glucose yeast extract agar were the least suitable. Overall, surface plating was superior to pour plating and, with the exception of one strain of A. acidocaldarius which grew better at 50 degrees C, incubation of K agar, ALI agar, and BAT agar plates at 43 degrees C or 50 degrees C resulted in recovery of equivalent numbers of spores. Essentially all viable spores were detected on media incubated for 3 days at 43 degrees C. The ability of one strain of each Alicyclobacillus species to grow in ten non carbonated commercially manufactured beverages at 30 degrees C and 43 degrees C was markedly affected by the composition of the beverages. Results show that surface plating samples on BAT agar, followed by incubating plates at 43 degrees C for 3 days provide the most suitable conditions to enumerate ten strains of three species of Alicyclobacillus most commonly responsible for spoilage of beverages. PMID- 17270302 TI - High level expression of a promising anti-idiotypic antibody fragment vaccine against HIV-1 in Pichia pastoris. AB - We have expressed the anti-idiotypic antibody 3H6 Fab directed against the HIV-1 broadly neutralising antibody 2F5 in methylotrophic yeast Pichia pastoris. The chimeric human/mouse Fab fragment was expressed under control of the inducible AOX1 promoter and secreted via the alpha mating factor leader of Saccharomyces cerevisiae. Bioreactor experiments showed the ability of the recombinant P. pastoris clone to secrete up to 260 mg/L Fab fragment in the culture supernatant during a five days cultivation time. Codon optimisation of the Fab expression cassette gave no further improvement of specific productivity when comparing 12 clones of each construct. The subsequent purification of Fab containing supernatants was done by anion exchange and size-exclusion chromatography with a recovery resulting in 70% of the recombinant protein. For verification of the suitability of the expression system we characterised the expressed protein with respect to both, its specificity and binding affinity and could not detect any significant difference between products from yeast derived and the hybridoma derived product. Finally we tested the implicit requirement of the carbohydrate moiety in the H2 loop of the original 3H6 antibody by introducing an asparagine to alanine replacement and, in a second experiment, inhibition of N-glycosylation by tunicamycin treatment. Biochemical analysis confirmed that the N-glycosylation does not contribute to the binding properties of 3H6. PMID- 17270303 TI - Topical iodine facilitates transdermal delivery of insulin. AB - Transdermal delivery of insulin is a non-invasive alternative to the subcutaneous injection of insulin in diabetic patients. It has been found that skin pretreatment with iodine followed by a dermal application of insulin results in reduced glucose and elevated hormone levels in the plasma. Topical iodine protects the dermally applied insulin presumably by inactivation of endogenous sulfhydryls such as glutathione and gamma glutamylcysteine which can reduce the disulfide bonds of the hormone. Thus, the effect of iodine is mediated by retaining the potency of the hormone during its penetration via the skin into the circulation. The proposed procedure might be applicable for additional disulfide containing peptides such as calcitonin, somatostatin, oxytocin/vasopressin and their analogs. PMID- 17270305 TI - Applications of carrier erythrocytes in delivery of biopharmaceuticals. AB - Carrier erythrocytes, resealed erythrocytes loaded by a drug or other therapeutic agents, have been exploited extensively in recent years for both temporally and spatially controlled delivery of a wide variety of drugs and other bioactive agents owing to their remarkable degree of biocompatibility, biodegradability and a series of other potential advantages. Biopharmaceuticals, therapeutically significant peptides and proteins, nucleic acid-based biologicals, antigens and vaccines, are among the recently focused pharmaceuticals for being delivered using carrier erythrocytes. In this article, the potential applications of erythrocytes in drug delivery have been reviewed with a particular stress on the studies and laboratory experiences on successful erythrocyte loading and characterization of the different classes of biopharmaceuticals. PMID- 17270304 TI - Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle. AB - Naked plasmid DNA (pDNA)-based gene therapy has low delivery efficiency, and consequently, low therapeutic effect. We present a biodegradable nonionic triblock copolymer, PEG(13)-PLGA(10)-PEG(13), to enhance gene delivery efficiency in skeletal muscle. Effects of PEG(13)-PLGA(10)-PEG(13) on physicochemical properties of pDNA were evaluated by atomic force microscopy (AFM) imaging, gel electrophoresis and zeta-potential analysis. AFM imaging suggested a slightly compacted structure of pDNA when it was mixed with the polymer, while zeta potential measurement indicated an increased surface potential of negatively charged pDNA. PEG(13)-PLGA(10)-PEG(13) showed a relatively lower toxicity compared to Pluronic P85 in a skeletal muscle cell line. The luciferase expression of pDNA delivered in 0.25% polymer solution was up to three orders of magnitude more than branched polyethylenimine (bPEI(25 k))/pDNA and three times more than that of naked pDNA five days after intramuscular administration. This in vivo gene delivery enhancement was also observed displaying a two-fold higher expression of human vascular endothelial growth factor (VEGF). Based on fluorescence labeled pDNA distribution, it is speculated that the greater diffusivity of PEG(13)-PLGA(10)-PEG(13)/pDNA compared to bPEI(25 k)/pDNA accounts for better transfection efficiency in vivo. To summarize, combining PEG(13) PLGA(10)-PEG(13) with pDNA possesses the potential to improve gene delivery efficiency in skeletal muscle. PMID- 17270306 TI - Enhancement of skin permeation of high molecular compounds by a combination of microneedle pretreatment and iontophoresis. AB - A combination of microneedle pretreatment and iontophoresis was evaluated for the potential to increase skin permeation of drugs. Two model compounds with low and high molecular D(2)O and fluorescein isothiocyanate (FITC)-dextrans (FD-4, FD-10, FD-40, FD-70 and FD-2000; average molecular weight of 3.8, 10.1, 39.0, 71.2 and 200.0 kDa), respectively, were used and the effect of microneedle pretreatment and iontophoresis on their in vitro permeability was evaluated using excised hairless rat skin with a 2-chamber diffusion cell. Convective solvent flow through the skin was measured using a set of calibrated capillaries attached to the diffusion cell. The following results were obtained: (1) convective solvent flow (electroosmosis) during iontophoresis through microneedle-pretreated skin, 2.62+/-0.32 microL/cm(2)/h, was almost the same as through intact skin, 2.71+/ 0.25 microL/cm(2)/h, and (2) the combination of microneedle pretreatment and subsequent iontophoresis significantly enhanced FD flux compared with microneedle pretreatment alone or iontophoresis alone, whereas no synergistic effect was found on the flux of D(2)O. These results suggest that the combination of iontophoresis with microneedle pretreatment may be a useful means to increase skin permeation of high molecular compounds. PMID- 17270307 TI - A novel approach using functional peptides for efficient intestinal absorption of insulin. AB - The aim of this study was to evaluate whether oligoarginine, a cell-penetrating peptide (CPP), can improve intestinal absorption of insulin in rats. Peptides composed of six (R(6)), eight (R(8)) and 10 (R(10)) residues of arginine were used as the CPP. No insulin absorption was observed following administration of insulin solution alone; however, insulin absorption increased dramatically after coadministration of the D-form of R(6) (D-R(6)) and the L-form of R(6) (L-R(6)) in a dose-dependent manner. The effects on insulin absorption were more pronounced for D-R(6) than for L-R(6). Among oligoarginines composed of six, eight, or 10 arginine residues, D-R(8) showed the strongest enhancing effects on insulin intestinal absorption. In contrast, intestinal absorption of other model hydrophilic macromolecules, interferon-beta and fluorescein isothiocyanate labeled dextran 4400, was not affected by coadministration with oligoarginine. Pretreatment by the effective dose of L-R(6) did not induce lactate dehydrogenase leakage or histological damage, suggesting that oligoarginine has no untoward effect on the intestinal mucosa. Our data demonstrate that coadministration of oligoarginine increases intestinal insulin absorption markedly without causing detectable damage in cellular integrity and that the covalent binding between insulin and oligoarginine is not necessary for this effect. We conclude that oligoarginines are likely to become powerful tools for overcoming the low permeability of insulin through the epithelial cell membrane, the major barrier to oral insulin delivery. PMID- 17270308 TI - Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium. AB - Vascular drug targeting may improve therapies, yet a thorough understanding of the factors that regulate effects of drugs directed to the endothelium is needed to translate this approach into the clinical domain. To define factors modulating the efficacy and effects of endothelial targeting, we used a model enzyme (glucose oxidase, GOX) coupled with monoclonal antibodies (anti-TM(34) or anti TM(201)) to distinct epitopes of thrombomodulin, a surface determinant enriched in the pulmonary endothelium. GOX delivery results in conversion of glucose and oxygen into H(2)O(2) leading to lung damage, a clear physiologic endpoint. Results of in vivo studies in mice showed that the efficiency of cargo delivery and its effect are influenced by a number of factors including: 1) The level of pulmonary uptake of the targeting antibody (anti-TM(201) was more efficient than anti-TM(34)); 2) The amount of an active drug delivered to the target; 3) The amount of target antigen on the endothelium (animals with suppressed TM levels showed less targeting); and, 4) The substrate availability for the enzyme cargo in the target tissue (hyperoxia augmented GOX-induced injury). Therefore, both activities of the conjugates and biological factors control targeting and effects of enzymatic cargo. Understanding the nature of such "modulating biological factors" will hopefully allow optimization and ultimately applications of drug targeting for "individualized" pharmacotherapy. PMID- 17270310 TI - Estimation of influence of gastric emptying on shape of glucose concentration time profile measured in oral glucose tolerance test. AB - AIMS: To develop a model for simulations of processes in the oral glucose tolerance test (OGTT), using tools of the theory of dynamic systems. METHODS: Frequent sampling OGTT was performed in 13 healthy subjects (6 males and 7 females). Subsequently, employing glucose and insulin concentration-time profiles of the subjects, the model was developed. RESULTS: In all subjects the model was able to simulate influences of the insulin plasma concentration and gastric emptying rate on glucose concentration and to determine time profiles of glucose fractions retained in stomach. CONCLUSIONS: The approach presented represents an opportunity for building models for data analyses in OGTT. PMID- 17270309 TI - Determination of the antioxidant status of plasma from type 2 diabetic patients. AB - An increase in oxidizing response above a certain threshold produces, in the absence of a concomitant rise in antioxidant/reducing response, oxidative stress that is associated with complications in diabetes. A simple technique involving reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye has been developed in order to determine quantitatively the antioxidant status of plasma. MTT (50microL; 5.0mg/mL in PBS) was incubated with plasma (100microL) in PBS for 30, 60 or 120min at 37 degrees C, the reaction terminated by addition of 1.0mL of 0.04M hydrochloric acid in isopropanol and the absorbance measured at 570nm. The modulation by plasma of the generation of reactive oxygen species (ROS) in 12,13-phorbol dibutyrate (PDB)-stimulated granulocytes was evaluated using a chemiluminescence luminol-dependent assay. Plasma from healthy subjects (n=15) showed significantly higher antioxidant status (p<0.05) over all time periods studied compared with plasma from diabetic patients (n=27). MTT was directly reduced by plasma although platelets were not involved. Moreover, the reduction of MTT by bovine serum albumin at levels equivalent to the concentration of human serum albumin in plasma was much lower. The antioxidant status of plasma, as evaluated by MTT dye reduction, may reflect an antioxidant response since ROS generation in PDB-stimulated granulocytes was rapidly down regulated by the presence of plasma (3.3-fold in diabetic patients and 5.8-fold in healthy subjects) confirming the lower antioxidant activity of plasma from diabetic patients. The results demonstrate that extracellular reduction of MTT by plasma may occur via enzymatic and non-enzymatic processes. PMID- 17270311 TI - Risk adjustment and risk selection in Europe: 6 years later. AB - In this paper we analyse the developments concerning risk adjustment and risk selection in Belgium, Germany, Israel, the Netherlands and Switzerland in the period 2000-2006. Since 2000 two major trends can be observed. On the one hand the risk adjustment systems have been improved, for example, by adding relevant health-based risk adjusters. On the other hand in all five countries there is evidence of increasing risk selection, which increasingly becomes a problem, in particular in Germany and Switzerland. Some potential explanations are given for these seemingly contradictory observations. Since the mid-1990s citizens in these countries can regularly switch sickness fund, which should stimulate the sickness funds to improve efficiency in health care production and to respond to consumers' preferences. When looking at managed care there are some weak signals of increasing managed care activities by individual sickness funds in all countries (except Belgium). However, with imperfect risk adjustment, such as in Israel and Switzerland, insurers will integrate their managed care activities with their selection activities, which may have adverse effects for society, even if all insurers are equally successful in selection. The conclusion is that good risk adjustment is an essential pre-condition for reaping the benefits of a competitive health insurance market. Without good risk adjustment the disadvantages of a competitive insurance market may outweigh its advantages. PMID- 17270312 TI - SINERGIA laparoscopic virtual reality simulator: didactic design and technical development. AB - VR laparoscopic simulators have demonstrated its validity in recent studies, and research should be directed towards a high training effectiveness and efficacy. In this direction, an insight into simulators' didactic design and technical development is provided, by describing the methodology followed in the building of the SINERGIA simulator. It departs from a clear analysis of training needs driven by a surgical training curriculum. Existing solutions and validation studies are an important reference for the definition of specifications, which are described with a suitable use of simulation technologies. Five new didactic exercises are proposed to train some of the basic laparoscopic skills. Simulator construction has required existing algorithms and the development of a particle based biomechanical model, called PARSYS, and a collision handling solution based in a multi-point strategy. The resulting VR laparoscopic simulator includes new exercises and enhanced simulation technologies, and is finding a very good acceptance among surgeons. PMID- 17270313 TI - Differences between small-cell lung cancer and non-small-cell lung cancer among tobacco smokers. AB - It is known that smoking increases the risk for all histological subtypes of lung cancer. To date, the factors that determine why some patients develop small-cell lung cancer (SCLC) while others develop non-small-cell lung cancer (NSCLC) remain unknown. We compared the characteristics of 774 smokers with SCLC and NSCLC diagnosed during the period January 1999 till December 2002. Multivariate logistic regression was used to estimate the odds ratio (OR) with 95% CI. Testing of linear trend across categories of pack-years was also conducted. Six hundred and sixty-five NSCLC were compared to 109 SCLC. Among SCLC, there were significantly more females (20.2% versus 12.8%), current-smokers (81.7% versus 71.9%) as well as smokers who had smoked more than 40 pack-years (75.6% versus 50.3%). Comparing SCLC with NSCLC among the men only, having smoked more than 40 pack-years was associated with a significantly elevated odds ratio (OR) of 3.71 of developing SCLC (95% CI, 1.05-13.1; p=0.041). There was a decreasing trend in OR with increasing smoking cessation period. When comparing SCLC with adenocarcinoma, the women had a higher OR of 2.37 of developing SCLC (95% CI, 1.05-5.31; p=0.037) compared to the men. Our findings suggest that cumulative smoking exposure in terms of pack-years smoked is an important determining factor for the preferred development of SCLC among smokers. PMID- 17270314 TI - Prevalence of stratified epithelium-specific antinuclear antibodies in 138 patients with lichen planus. AB - BACKGROUND: Antibodies to stratified epithelia characterize chronic ulcerative stomatitis, an entity that very closely resembles erosive lichen planus both clinically and histologically. These antibodies are directed against a 70-kd antigen. OBJECTIVE: Our aim was to verify whether antibodies to stratified epithelia are present in patients with common lichen planus. PATIENTS AND METHODS: One hundred thirty-eight patients with various forms of lichen planus were studied. Indirect immunofluorescence was performed on both monkey esophagus and HEp2-2000 cells. Immunoblotting was done with cultured keratinocytes used as the source antigen. RESULTS: Nineteen patients had antibodies to stratified epithelia (in 9 directed against an antigen of 70 kd). Forty-eight patients had circulating antibodies detected by indirect immunofluorescence on both monkey esophagus and HEp2-2000 cells (in 7 directed against an antigen of 70 kd). Indirect immunofluorescence was positive only on HEp2-2000 cells in 21 patients. Indirect immunofluorescence was negative in 50 patients on both HEp2-2000 cells and monkey esophagus. None of the last 71 patients had antibodies directed to an antigen of 70 kd. LIMITATIONS: This is a serological study; results from direct immunofluorescence studies would be interesting. CONCLUSION: Antibodies to stratified epithelia directed to an antigen of 70 kd are not exclusive to chronic ulcerative stomatitis, but are also present in some patients with lichen planus. PMID- 17270315 TI - A randomized bilateral vehicle-controlled study of eflornithine cream combined with laser treatment versus laser treatment alone for facial hirsutism in women. AB - BACKGROUND AND OBJECTIVE: Although there are a multitude of therapeutic modalities for removing unwanted facial hair in women, there is very little information on using the newer medical treatment approaches in combination. This study was designed to determine whether topical eflornithine can enhance the efficacy of laser hair removal. DESIGN: This was a randomized, double-blind, placebo-controlled, right-left comparison study of eflornithine cream combined with laser treatment versus laser alone for treating unwanted hair on the upper lip in women. All subjects underwent treatment to the entire upper lip with a long pulse alexandrite laser (10-40 ms pulse duration) at fluences of 7 to 40 J/cm(2). Laser treatments were performed every 4 weeks for up to 6 sessions. Each patient also applied either eflornithine or placebo cream twice daily to each side of the upper lip in a double-blinded manner. Subjects were evaluated for safety by recording adverse events and for efficacy via (1) investigator global scoring, (2) patient self assessment, and (3) hair count analysis. RESULTS: Both treatment modalities were well tolerated by the 31 evaluable patients. All 3 outcome measures showed significantly better results in favor of eflornithine plus laser versus laser treatment alone. At the end of the study, complete or almost complete hair removal was achieved in 29 of 31 (93.5%) of the eflornithine laser-treated sites versus 21 of 31 (67.9%) for the placebo cream-laser-treated sites (P = .021, McNemar test). Statistically significant differences in favor of eflornithine were likewise demonstrated at the final assessment through blinded patient grading (13/31 patients [41.9%] thought that the eflornithine was superior to placebo, P = .029, Poisson regression) and hair count analysis (P < .01, paired t test). LIMITATIONS: This is a single-center study that did not determine whether the differences noted above last beyond 6 months. CONCLUSIONS: On the basis of both investigator and patient assessments and hair count analysis, we have demonstrated that the addition of eflornithine to laser hair removal results in a more rapid and complete reduction of unwanted facial hair in women when the combination is used for up to 6 months. PMID- 17270316 TI - [Immunization of adults against varicella and herpes zoster]. AB - PURPOSE: Following the commercialisation in France of the varicella vaccine and the European marketing authorization for a vaccine against zoster, this article intends to review the epidemiology of varicella and herpes zoster, to expose the characteristics of the available vaccines, and to consider the advantages and caveats of the different immunisation strategies. CURRENT KNOWLEDGE AND KEY POINTS: In France, from 550.000 to 750.000 cases of varicella are reported each year, which result in more than 3.500 hospitalizations and about 20 deaths. Subjects>or=15 years old represent 8.3% of the total number of cases of varicella, 26% of varicella-related hospitalisations and 69% of all varicella related deaths. The susceptibility rate for the 15 years old is 10,3 and 79% of these non-immune subjects are expected to contract varicella. The vaccines currently marketed against varicella are safe, have a good immunogenicity and remain effective over the evaluated periods. Two vaccination strategies are considered: a generalized vaccination of the infants and children, or a vaccination targeted against high-risk populations and non-immune teenagers and adults. The incidence of herpes zoster is estimated in France at 235.000 new cases per year, from which 1% is hospitalized. A live attenuated vaccine using the same strain as the varicella vaccine, but at a much higher dose, proved its efficacy in terms of reducing shingles and postherpetic neuralgia incidences, of 51 and 67% respectively. This vaccine received a marketing authorisation in France, for adults>or=60 years old. FUTURE PROSPECTS: Uncertainties about the impact of vaccination on varicella and herpes zoster epidemiology have yet to be solved, such as the potential increase in herpes zoster incidence or in the absolute number of diagnosed varicella cases in older age groups, or the loss of vaccination-induced immunity with time. These questions demonstrate the need for an operational real-time surveillance network to monitor varicella and herpes zoster incidence in the setting of general population immunisation. PMID- 17270317 TI - Fish oil supplementation does not alter energy efficiency in healthy males. AB - BACKGROUND AND AIMS: Fish oil (FO) supplementation prevents the development of obesity and insulin resistance, and upregulate the expression of UCP3 in skeletal muscle in rodents. This may represent indirect evidence that FO promotes fat oxidation and/or alter energy efficiency. The aim of this study was to evaluate whether such effects can be observed in humans. The metabolic effects of FO were assessed during exercise in order to obtain a direct measurement of energy efficiency. METHODS: Eight healthy male volunteers were studied with and without supplementation with 7.2 g/day FO (including 1.1 g/day eicosopentaenoic acid and 0.7 g/day decosahexaenoic acid) during 14 days. Their VO(2 max) was measured on cycle ergometer. Thereafter, energy metabolism (substrate oxidation, energy expenditure and energy efficiency) was assessed during a 30 min cycling exercise at 50% VO(2 max) performed 2 h 30 after a standardized, high carbohydrate breakfast. RESULTS: VO(2 max) was 38.6+/-2.2 after FO and 38.4+/-2.0 (mL x kg(-1) x min(-1)) in control conditions (NS). Basal plasma glucose, insulin and NEFA concentrations, and energy metabolism were similar with FO and in controls. During exercise, the increases in plasma NEFA concentrations, energy expenditure, glucose and lipid oxidation, and the decreases in glycaemia and insulinemia were not altered by FO intake. Energy efficiency was 22.4+/-0.6% after FO vs 21.8+/ 0.7% in controls. In order to ascertain that the absence of effects of FO was not due to consumption of a carbohydrate meal immediately before exercise, 4 of the 8 subjects were re-studied in fasting conditions, FO also failed to alter energy efficiency in this subset of studies. CONCLUSION: FO supplementation did not significantly alter energy metabolism and energy efficiency during exercise in healthy humans. PMID- 17270318 TI - Evaluation of the National Notifiable Disease Surveillance System in Taiwan: an example of varicella reporting. AB - Despite the mandatory reporting by laws, the incompleteness of notifiable infectious disease reporting is well-documented in many countries for various diseases. The purpose of this study is to investigate the completeness of varicella reporting in Taiwan. Annual reports of National Notifiable Disease Surveillance System in Taiwan were compared to the annual outpatient claims of National Health Insurance (NHI) in the years of 2000, 2001, and 2002. Age and area-specific reporting rates of varicella were calculated by dividing the respective reported cases by the number of incidence cases. The reporting rate was the highest in aged 0 year in all years, followed by the 20-29- and 30-39 year groups. The reporting rate in each age group increased gradually during the study period. Other than Taipei City, the reporting rates in all regions were below 9% during this period. This study suggested that varicella reporting rate is very low in Taiwan. In addition, the reporting rates were inconsistent in 2000 2002, making the estimation of prevalence and vaccine efficacy using data from the National Notifiable Disease Surveillance System almost impossible. This study indicated that the physicians in Taiwan should improve their knowledge and attitude toward notifiable infectious diseases. PMID- 17270319 TI - Intranasal immunization with phosphorylcholine induces antigen specific mucosal and systemic immune responses in mice. AB - Phosphorylcholine (PC) is a structural component of a wide variety of pathogens including Streptococcus pneumoniae and Haemophilus influenzae, and anti-PC immune responses are known to protect mice against invasive bacterial diseases. The present study tested the capability of PC as an intranasal plurispecific vaccine against upper airway infections. BALB/c mice immunized with intranasal PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT) as a mucosal adjuvant showed increased PC-specific IgM in serum, IgA in nasal wash and saliva, and numbers of PC-specific nasal and splenic antibody producing cells. Enhanced production of IL 4 and IFN-gamma by CD4+ T cells indicated the participation of Th2- and Th1-type cells. Salivary IgA antibodies produced by intranasal immunization with PC-KLH plus CT reacted to most strains of S. pneumoniae and H. influenzae. Further we demonstrated that the clearance of S. pneumoniae and H. influenzae from the nasal tract was significantly enhanced by nasal immunization with PC-KLH and CT. Thus, intranasal vaccination to induce PC-specific immune responses might help to prevent upper airway infections caused by S. pneumoniae and H. influenzae. PMID- 17270322 TI - Protective immunity against Ixodes ricinus induced by a salivary serpin. AB - Iris is a specific elastase inhibitor expressed in the salivary glands of the hard tick Ixodes ricinus. It belongs to the superfamily of serpins and interferes with both haemostasis and the immune response of the host. In this study, we first show that Iris is expressed in nymphs but not in the female midgut nor in males. We also show that Iris is present in the saliva. To examine its potency as anti-tick vaccine candidate, we set up three models of I. ricinus infestation on immunized animals: nymphs on mice, and adults and nymphs on rabbits. We report the rise of neutralizing antibodies following immunization of rabbits and mice. This comes with a significant protective immunity against ticks in rabbits only, resulting in a 30% mortality rate and a diminution of weight gain in both nymphs and adults and a prolongation of blood feeding time in adults. This is the first report on an anti-tick vaccine trial on I. ricinus using a protein able to interact with both host immunity and haemostasis, as a vaccinating antigen. PMID- 17270320 TI - Comparison of the safety and immunogenicity of concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults. AB - The annual contact for influenza vaccination provides an opportunity to ensure that adults have received other recommended vaccines such as Tdap. Healthy 19-64 year-olds were randomized to receive concomitant administration of Tdap and influenza vaccines or influenza vaccine followed (in 4-6 weeks by) Tdap. 720 participants were enrolled. No clinically relevant between-group differences were observed in the rates or severities of erythema, swelling, or pain at the Tdap injection site. Injection-site pain was the most commonly reported adverse event (66.6% concomitant administration group versus 60.8% sequential administration group); most pain was graded as mild and resolved by day 3. Seroprotection and seroresponse rates for all influenza strains were comparable between the two groups. For diphtheria and tetanus, seroprotection rates and post-vaccination GMTs were non-inferior in the concomitant administration group compared to the sequential administration group. A trend for lower antibody responses to pertussis antigens PT, FHA, and FIM was observed after concomitant administration and, for PRN, this difference failed the non-inferiority criteria. While there is a small diminution in antibody response to tetanus and pertussis antigens, concomitant administration of Tdap and influenza vaccine was well tolerated and immunogenic and may offer practical advantages including convenience, compliance, and cost-savings. PMID- 17270323 TI - Systems integration: an effective and innovative response to emerging biological threats. AB - A rapid and effective development of vaccines and other prophylactics, as well as novel therapeutics, against emerging threats requires the development and implementation of novel strategies. One such strategy is the integrator approach. This approach utilizes an integrated development team comprising expertise in program management, scientific management, clinical research, preclinical/nonclinical development, manufacturing, testing, risk management, quality assurance, and regulatory strategy and compliance. Key to the success of this approach is the successful management of subcontracted work, as well as the seamless integration of multiple systems and data inputs into a coherent development plan. PMID- 17270324 TI - Plutonium concentration and 240Pu/239Pu atomic ratio in liver of squid collected in the coastal sea areas of Japan. AB - Plutonium isotopes, 239Pu and 240Pu, were measured in liver samples from Surume squid using a sector-field high resolution ICP-MS after radiochemical purification. Surume squid samples were obtained from nine landing ports in Japanese inshore during fishery season from September to December 2002. Concentrations of 239Pu and 240Pu ranged from 1.5 to 28 mBq kg(-1) and 1.1 to 24 mBq kg(-1), respectively. Plutonium (239,240Pu) concentrations in liver were several thousand times higher than levels found in seawater. The concentration factor (CF) compared to seawater for 239,240Pu and 13 other elements ranged from 10(0) to 10(7). The CF values for 239,240Pu, V and Th were 10(2)-10(4). Pu had an intermediate CF between conservative and scavenged elements. 240Pu/239Pu atomic ratios in the squid liver ranged from 0.177 to 0.237 which were slightly higher than 0.178+/-0.014 for global fallout. The variations of 240Pu/239Pu atomic ratios in ocean currents with different source functions are important for interpreting high 240Pu/239Pu atomic ratios in Surume squid liver. It seems likely that Pu with high 240Pu/239Pu atomic ratio is continuously transported through the solubilization and seawater transport from the North Equatorial Current to Kuroshio and its branch, Tsushima Current. By assuming that Pu found in Surume squid liver is a mixture of global fallout Pu (0.178) and close-in fallout Pu with high 240Pu/239Pu atomic ratio (0.30-0.36) around Bikini Atoll, Pu contribution from Bikini close-in fallout Pu accounts for close to 35% of the whole plutonium in Surume squid liver. These results highlight that Surume squid is a useful organism for evaluating environmental Pu levels of larger sea area and facilitate the development of models to understand oceanic transport of close in fallout Pu from Bikini Atoll. PMID- 17270325 TI - A report of two linked studies of knowledge and attitudes to prenatal screening and testing in adults of reproductive age in Japan and the UK. AB - BACKGROUND: prenatal screening for fetal abnormality is being offered routinely in many countries. The need for informed consent demands that the nature of screening is understood by prospective parents, but the opportunities for providing information early in pregnancy before decision-making may be limited. OBJECTIVE: to assess the knowledge about, and attitudes to, prenatal screening in adults of reproductive age in two countries. DESIGN: two groups of adults were surveyed using a specifically designed tool to assess knowledge about fetal abnormalities and potential screening tests, attitudes to screening and termination of pregnancy, and information required by parents before making decisions. SETTING AND PARTICIPANTS: 90 participants were surveyed in Japan, 72% of whom were pregnant or had a partner who was pregnant; 93 participants were surveyed in the UK, none of whom were pregnant. All respondents were aged between 18 and 45 years. MEASUREMENTS: demographic data were collected and analysed. Frequencies were calculated for each questionnaire response. A series of t-tests and chi(2) tests were used to assess differences between the two groups. Free text data were analysed using content analysis. FINDINGS: overall knowledge of prenatal tests and the conditions for which screening is offered was low in both groups. Significant differences exist between the perception of the conditions for which screening or testing can be offered and the types of conditions that can actually be detected prenatally. Most respondents in both countries would consider termination of pregnancy for fetal abnormality. The information most frequently cited by respondents as important when deciding about testing were the chances of damage to the health of fetus, mother, or both. KEY CONCLUSIONS: women and men of reproductive age in the groups studied are not well-prepared to make decisions about screening or testing in pregnancy. IMPLICATIONS FOR PRACTICE: improvements in preconceptual education on prenatal screening and testing may be required to ensure prospective parents can make informed decisions in early pregnancy. PMID- 17270326 TI - A state-wide review of hospital postnatal care in Victoria, Australia: the views and experiences of midwives. AB - OBJECTIVE: to describe midwives' views and experiences of the provision and organisation of hospital-based postnatal care. DESIGN: semi-structured interviews with key informants who provide hospital-based postnatal care. SETTING: public hospitals in Victoria, Australia. PARTICIPANTS: clinical midwives and midwifery managers (n=33). FINDINGS: midwives remain positive about working in hospital based postnatal care; however, their satisfaction is influenced by barriers to effective care beyond their control, which specifically limit the time available to spend with women. They described many constraints on their practice, including the length of hospital stay, inadequate midwife-to-woman ratios, the busyness of postnatal units, and the effect of visitors. Midwives viewed the aims of postnatal care to include education and support of women with breastfeeding and parenting skills, and helping in women's physical recovery after pregnancy and birth. Midwives' perceptions of the factors that influence women's satisfaction with postnatal care are consistent with what we know are women's views: continuity of care, individualised unrushed care, and flexibility in routine practices. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: midwives' views and experiences of hospital-based postnatal care are in accordance with women's views and experiences. They are less than satisfied with hospital-based postnatal care, and they perceive a need for individualised, unrushed, flexible care. With evidence from both providers and women about the unsatisfactory nature of the current provision and organisation of hospital-based postnatal care, new approaches to this episode of care need to be explored. PMID- 17270327 TI - The forgotten victims of the conflict in Iraq. PMID- 17270328 TI - Investigation into the affect of cementing techniques on load transfer in the resurfaced femoral head: a multi-femur finite element analysis. AB - BACKGROUND: Femoral head resurfacing is a popular procedure for younger active hip replacement patients. Two major cementing techniques are used in femoral component fixation; producing varying cement mantle thicknesses. Each technique has benefits, but it is not known if cement mantle thickness is detrimental to load transfer within the proximal femur. METHODS: This study uses computer tomography based finite element analysis to determine the effect of cement mantle thickness on strain in the resurfaced femoral head. A group of 16 femurs were investigated to take into account inter-patient variation; a factor often over looked in such studies. FINDINGS: Results showed strain in the proximal femoral head to decrease with increasing cement thickness, with a slight increase in strain in the posterior-superior neck. Cementing of the implant guide-pin produced marked reductions in strain in the head and neck except for the posterior-inferior neck; where it increased slightly. INTERPRETATION: The study concluded that a thicker cement mantle increases strain shielding within the superior resurfaced femoral head; although short to medium term clinical trials do not suggest these factors to be of much concern. The analysis also found strain to increase around the inferior head-neck junction with a thinner mantle. Cementing the guide pin resulted in increased strain shielding whilst simultaneously shifting peak loads distally along the femoral neck. This work found that modelling a group of femurs was a useful tool for better interpreting the loading in the resurfaced femur. PMID- 17270329 TI - Osteosynthesis of supracondylar humerus fractures in children: a biomechanical comparison of four techniques. AB - BACKGROUND: Crossed k-wire osteosynthesis is a widely used procedure for displaced supracondylar humerus fractures in children, but the rate of secondary displacements is up to 31%. Alternative techniques including casts, elastic stable intramedullary nailing, and the fixateur extern, have been used, but there are no biomechanical data comparing these methods. We developed a biomechanical model to compare four osteosynthesis techniques for stabilizing supracondylar humerus fractures in children. METHODS: An osteotomy to simulate a fracture was made in a total of 32 adult cadaver humeri. The pseudofractures were then stabilized by crossed k-wires, elastic nailing, a fixateur extern with either k wires, or Schanz screws. We measured the stiffness values in flexion and extension and torsion with static loading. The movements in cyclic loading were chosen to resemble the mechanism described in the development of a clinical cubitus varus. FINDINGS: No significant differences were found with static loading. With cyclic loading all methods showed an irreversible torsional deformation less than 20 degrees . Crossed k-wires and elastic nailing showed significantly lower reversible torsional deformation than the external fixateurs. INTERPRETATION: Our biomechanical data reveal that the crossed k-wires have the highest stiffness and lowest loss of reduction under cyclic loading. The external fixators proved to be good alternatives. PMID- 17270330 TI - Integrating theoretical, measurement, and intervention models of youth social competence. AB - Social competence is of great interest to developmental psychopathologists and is assessed frequently in both basic and applied research. A review of the literature reveals not only significant heterogeneity in definitions of this construct but an apparent disconnect between theoretical, measurement, and intervention models of competence in youth. This paper attempts to integrate these disparate enterprises by identifying four types of predictors theorists have associated with competence--child, behavior, situation, and judge--and critiquing common models in light of these dimensions. In general, assessment and intervention approaches appear less complex than theoretical conceptualizations of competence. When considering whether to incorporate additional predictors, notably situation- and judge-level factors, into these models, researchers must weigh parsimony versus the model misspecification that results from omitting important variables. Basic research that may assist in making these decisions is identified. PMID- 17270331 TI - Species-specific inhalable exposures in the nickel industry: a new approach for deriving inhalation occupational exposure limits. AB - The American Conference of Governmental Industrial Hygienists (ACGIH) and some regulatory authorities have revised their exposure limits for nickel and nickel compounds in workplaces based upon new sampling standards for inhalable nickel exposures. Others may be in the process of doing so. Safe standards for workplace exposures should utilize the most up-to-date health data on individual nickel species and should incorporate the principles of new sampling conventions that have been developed over the recent decades. The purpose of this paper is to review the basis for setting inhalable occupational exposure standards for the principal inorganic nickel species. It is hoped that this paper will (1) prompt companies in various nickel industry sectors to begin collecting the necessary inhalable aerosol measurements, speciation data, and particle-size information required to implement health-based sampling programs in the future, and (2) encourage regulators to derive species-specific, inhalable-based workplace standards for nickel and its inorganic compounds. PMID- 17270332 TI - 'Getting on with life': the experiences of older people using complementary health care. AB - Surprisingly few studies have explored the use of complementary medicine amongst older persons and existent research is typically restricted to those who can afford private treatment. The aim of the current qualitative study is to explore the experiences of older people using subsidised complementary health care. Semi structured interviews were conducted with 17 regular attendees of a single centre offering low cost complementary health care to the over-60's in London, UK. The sample was randomly drawn from the patient register and included patients from mixed social and ethnic backgrounds. Transcripts were analysed using interpretative phenomenological analysis (IPA). The core theme underlying participants' accounts related to the desire to 'get on with life' and maintain physical and social functioning within the constraints imposed by chronic conditions. Consequently, the physiological effects of treatment were highly valued, particularly reductions in pain and improved mobility. Psychological effects operated at a more subtle level, influencing perceptions of health and well-being. The empowering nature of treatment enabled participants to regain a sense of control over their health, which reduced anxiety and facilitated 'normal' functioning. The whole package care was perceived as an important source of support and reassurance in contrast to the impersonal experiences of orthodox medicine. Complementary health care was therefore perceived as an important adjunct to orthodox medicine, particularly in terms of its impact on everyday functioning and well-being. Implications for the quality of life of older people with complex health needs and limited access to private complementary health care are discussed. PMID- 17270334 TI - Is it possible to be dependent to Tianeptine, an antidepressant? A case report. AB - Tianeptine, an atypical tricyclic antidepressant, is one of the first chemical agents, like tricyclic antidepressants and selective serotonin re-uptake inhibitors (SSRIs), which are employed for the treatment of anxiety and depressive disorders. It is believed that tianeptine, unlike the SSRIs, is enhancing serotonin re-uptake the velocity of the cortical neurons in the lymbic system and hippocampal neurons. In literature, there are more examples of dependence cases of antidepressants, which have amphetaminergic effects, such as amineptine and tranylcipromine, than amitriptyline, fluoxetine and tianeptine. Contrary to the reports about using high dosages of tianeptine, case reports about misuse and dependence have revealed that the most common reason of dependence is the psychostimulant effect. In these cases, tolerance to tianeptine and the symptoms of depreviation in absence of the drug have been seen, and the history of dependence or abuse of any drug or alcohol, treatment for mood and/or personality disorders are mentioned as possible risks for the dependence to tianeptine. This report discusses the diagnosis and treatment of a tianeptine dependence case. The 34 year-old patient, who is in conflict with her own family members, does not have the history of dependence or abuse of any substances, except for smoking, had been using excessive doses of 750 mg/day of tianeptine for a year. PMID- 17270335 TI - Enamel - a "metallic-like" deformable biocomposite. AB - OBJECTIVES: The aim of this study is to compare the mechanical responses of enamel with dental-used metals and to show that enamel has mechanical properties similar to metals rather than ceramics. METHODS: Four dental-used metals: cast alloy, gold alloy, titanium and amalgam, were compared with enamel. Pure hydroxyapatite (HAP) was used as the ceramic analogue of enamel. A Berkovich and a spherical indenter were selected for nanoindentation tests. The stress-strain (H-a/R) curves and indentation creep behaviour were investigated and analyzed. RESULTS: Although the primary composition of enamel is hydroxyapatite, the indentation stress-strain curves and creep behaviour of enamel was totally different to HAP. Enamel had similar stress-strain response to that of cast alloy and gold alloy, all of which showed work-hardening effect. Titanium and amalgam had curves that showed lower stress at comparable strain than enamel and showed no work-hardening. Amalgam exhibited the greatest creep behaviour, followed by Titanium, enamel and gold alloy. Similar to HAP, the cast alloy had very limited creep response. Only enamel showed significant backcreep at minimum load. This may be a consequence of the memory behaviour of the minor protein component within enamel. CONCLUSIONS: The small remnant volume fraction of protein fragments have endowed enamel with metallic-like mechanical properties, which impart it with an ability to sustain repetitive cyclic contact loading over the life of the host. It may be better to choose metallic-like dental restorative materials to sustain the severe cyclic contact behaviour experienced and to protect the opposing teeth from excessive damages. PMID- 17270333 TI - A qualitative and quantitative review of cocaine-induced craving: the phenomenon of priming. AB - Drug-induced craving is thought to play an important role in relapse occasioned by a "slip", or an isolated use of a previously abused drug after a period of abstinence. Clinical experience suggests that acute exposure to cocaine elicits craving (hereafter referred to as "priming"); however, this has received surprisingly little attention in the clinical literature. AIMS: The intentions of this review are to provide a qualitative review of the literature as well as a more stringent quantitative review of the existence and presence of cocaine induced priming effects. METHODS: In order to determine whether priming effects occur following cocaine administration, we conducted qualitative and quantitative reviews of studies in which participants received cocaine under experimentally controlled conditions in the laboratory. RESULTS: The results of the qualitative review were equivocal, while the quantitative review revealed that cocaine administration was associated with a significant increase in craving for cocaine, and the effect size of this relationship was large. CONCLUSION: A review of the individual studies revealed marked variability, suggesting that priming effects did not occur consistently and that there may be factors that mediate or moderate the intensity of the priming effects induced by cocaine. The implications of these findings are discussed. PMID- 17270336 TI - Comparison of hands-off time during CPR with manual and semi-automatic defibrillation in a manikin model. AB - BACKGROUND: Rhythm analysis with current semi-automatic external defibrillators (AEDs) requires mandatory interruptions of chest compressions that may compromise the outcome after cardiopulmonary resuscitation (CPR). We hypothesised that interruptions would be shorter when the defibrillator was operated in manual mode by trained and certified ambulance personnel. MATERIALS AND METHODS: Sixteen pairs of ambulance personnel operated the defibrillator (Lifepak((R))12) in both semi-automatic (AED) and manual (MED) mode in a randomised, cross-over manikin CPR study, following the ERC 2000 Guidelines. RESULTS: Median time from last chest compression to shock delivery (with interquartile range) was 17s (13, 18) versus 11s (6, 15) (mean difference (95% CI) 6s (2, 10), p=0.004). Similarly, median time from shock delivery to resumed chest compressions was 25s (22, 26) versus 8s (7, 12) (median difference 13s, p=0.001) in the AED and MED groups, respectively. While sensitivity for identifying ventricular fibrillation (VF) in both modes and specificity in the AED mode were 100%, specificity was 89% in manual mode. Thus, some unwarranted shocks resulting in hands-off time (time without chest compressions) were given in manual mode. However, mean hands-off ratio (time without chest compressions divided by total resuscitation time) was still lower, 0.2s (0.1, 0.3) versus 0.3s (0.28, 0.32) in manual mode, mean difference 0.10s (0.05, 0.15), p=0.001. CONCLUSION: Paramedics performed CPR with less hands-off time before and after shocks on a manikin with manual compared to semi-automatic defibrillation following the 2000 Guidelines. However, 12% of the shocks given manually were inappropriate. PMID- 17270337 TI - Causes of obesity: looking beyond the hypothalamus. AB - The brain takes a primary position in the organism. We present the novel view that the brain gives priority to controlling its own adenosine triphosphate (ATP) concentration. It fulfils this tenet by orchestrating metabolism in the organism. The brain activates an energy-on-request system that directly couples cerebral supply with cerebral need. The request system is hierarchically organized among the cerebral hemispheres, the hypothalamus, and peripheral somatomotor, autonomic visceromotor, and the neuroendocrine-secretomotor neurons. The system initiates allocative behavior (i.e. allocation of energy from body to brain), ingestive behavior (intake of energy from the immediate environment), or exploratory behavior (foraging in the distant environment). Cerebral projections coordinate all three behavioral strategies in such a way that the brain's energy supply is guaranteed continuously. In an ongoing learning process, the brain's request system adapts to various environmental conditions and stressful challenges. Disruption of a cerebral energy-request pathway is critical to the development of obesity: if the brain fails to receive sufficient energy from the peripheral body, it compensates for the undersupply by increasing energy intake from the immediate environment, leaving the body with a surplus. Obesity develops in the long term. PMID- 17270338 TI - Intramural bladder leiomyoma appearing as a pelvic tumor: a case report. PMID- 17270339 TI - Assessing the US Clean Water Act 303(d) listing process for determining impairment of a waterbody. AB - This study evaluated the US Clean Water Act (CWA) Section 303(d) listing and delisting processes, based on historical and current federal and state guidelines, to determine whether there are regional differences in water quality assessment criteria used by various states to determine impairment of a waterbody for inclusion in the 303(d) list. A review of almost 50 total maximum daily load (TMDL) and delisting documents revealed that the basis for listing or delisting a waterbody varies considerably and that, in many cases, determination of impairment was based on insufficient water quality information. Historical USEPA guidance on the 303(d) listing and delisting processes has been generally broad, resulting in wide interpretation of the assessment criteria by various states. This has led to unclear or conflicting listing methodologies among states, leading to inconsistencies in impairment determination. Common problems include inconsistent data quality and quantity, differences in frequency of monitoring, variable interpretation of narrative water quality standards, and differences in specificity of implementation and monitoring plans, resulting in significant difference in the basis for listing and delisting waterbodies. In response, several states have taken the initiative to provide much more specific guidance for their internal agencies. Listing and delisting criteria are generally clearer at the state level, but the development of differing state guidance documents has resulted in diversity in the development of the 303(d) lists and in the process of delisting a waterbody. While state guidelines are better able to address local considerations, such as variations in climate, landuse, and water quality objectives, as well as social and economic preferences, the variation in listing criteria has led to inconsistencies across state boundaries in the levels of attainment of national water quality objectives. For stakeholders that participate in the 303(d) listing process within a particular state, these types of discrepancies may not have a significant impact. However, these inconsistencies can lead to confusion for some stakeholders who participate in the process in multiples states, and must deal with differing and sometimes conflicting requirements depending on the location of their facilities. PMID- 17270340 TI - Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study. AB - OBJECTIVE: To define the optimum tamoxifen dose for reducing bicalutamide (CASODEX) 150 mg monotherapy-induced breast events (ie, gynaecomastia or breast pain or both) without compromising disease control. METHODS: This was a double blind, parallel-group, multicentre trial in which 282 patients with prostate cancer were randomised to receive bicalutamide 150 mg/d plus either daily tamoxifen (1, 2.5, 5, 10, or 20mg) or placebo for 12 mo, followed by 12 mo of treatment with bicalutamide only. Primary end points were incidence of breast events and prostate-specific antigen (PSA) inhibition and were analysed at 6 mo (the primary analysis) and also at 12 and 24 mo. RESULTS: At 6 and 12 mo, tamoxifen decreased the incidence of breast events in a dose-dependent manner, with breast events observed in 86.2%, 60.0%, 55.3%, 23.5%, and 8.8% of patients receiving tamoxifen 1, 2.5, 5, 10, and 20 mg, respectively, compared with 96.7% of patients receiving placebo at 6 mo. At 24 mo (ie, after 12 mo of bicalutamide monotherapy), a high incidence of breast events was seen in all groups. There was no evidence of a negative effect on PSA inhibition at any assessment. Other nonbreast adverse effects were similar across groups, except for an increase in hot flushes with tamoxifen doses > or =5 mg. CONCLUSION: These findings suggest that prophylactic tamoxifen 20 mg/d is an effective dose for reduction of bicalutamide-induced breast events and does not appear to affect disease control based on PSA suppression. PMID- 17270341 TI - Editorial comment on: Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study. PMID- 17270343 TI - The adsorption of basic dye (Astrazon Blue FGRL) from aqueous solutions onto sepiolite, fly ash and apricot shell activated carbon: kinetic and equilibrium studies. AB - In this study, sepiolite, fly ash and apricot stone activated carbon (ASAC) were used as adsorbents for the investigation of the adsorption kinetics, isotherms and thermodynamic parameters of the basic dye (Astrazon Blue FGRL) from aqueous solutions at various concentrations (100-300 mg/L), adsorbent doses (3-12 g/L) and temperatures (303-323 K). The result showed that the adsorption capacity of the dye increased with increasing initial dye concentration, adsorbent dose and temperature. Three kinetic models, the pseudo-first-order, second-order, intraparticle diffusion, were used to predict the adsorption rate constants. The kinetics of adsorption of the basic dye followed pseudo-second-order kinetics. Equations were developed using the pseudo-second-order model which predicts the amount of the basic dye adsorbed at any contact time, initial dye concentration and adsorbent dose within the given range accurately. The adsorption equilibrium data obeyed Langmuir isotherm. The adsorption capacities (Q0) calculated from the Langmuir isotherm were 181.5 mg/g for ASAC, 155.5 mg/g for sepiolite and 128.2 mg/g for fly ash at 303 K. Thermodynamical parameters were also evaluated for the dye-adsorbent systems and revealed that the adsorption process was endothermic in nature. PMID- 17270342 TI - Effects of cannabinoid receptors on skeletal muscle oxidative pathways. AB - The endocannabinoids, a recently discovered endogenous, lipid derived, signaling system regulating energy metabolism, have effects on central and peripheral energy metabolism predominantly via the cannabinoid receptor type 1 (CB1). CB1 is expressed centrally in the hypothalamus and nucleus accumbens and peripherally in adipocytes and skeletal muscle. This study determined the effect of endocannabinoids on the expression of genes regulating energy metabolism in human skeletal muscle. Primary cultures of myotubes (lean and obese; n=3/group) were treated with the cannabinoid receptor agonist, anandamide (AEA) (0.2 and 5microM) and the CB1 specific antagonist AM251 (0.2 and 5microM) separately and in combination for 24h. The expression of mRNA for AMP-activated protein kinase (AMPK) alpha 1 (alpha1) and alpha 2 (alpha2), pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha) were determined using 'Real Time' RT-PCR. AMPKalpha1 mRNA increased in lean and obese myotubes in response to AM251 (P<0.05). AEA inhibited the effect of AM251 on AMPKalpha1 mRNA levels in myotubes from lean and obese subjects (P<0.05); the dose-response curve was shifted to the left in the obese. In response to AM251, irrespective of the presence of AEA, PDK4 expression was decreased in lean and obese myotubes (P<0.05). Taken together these data suggest that endocannabinoids regulate pathways affecting skeletal muscle oxidation, effects particularly evident in myotubes from obese individuals. PMID- 17270344 TI - Finite element modeling of contaminant transport in soils including the effect of chemical reactions. AB - The movement of chemicals through soils to the groundwater is a major cause of degradation of water resources. In many cases, serious human and stock health implications are associated with this form of pollution. Recent studies have shown that the current models and methods are not able to adequately describe the leaching of nutrients through soils, often underestimating the risk of groundwater contamination by surface-applied chemicals, and overestimating the concentration of resident solutes. Furthermore, the effect of chemical reactions on the fate and transport of contaminants is not included in many of the existing numerical models for contaminant transport. In this paper a numerical model is presented for simulation of the flow of water and air and contaminant transport through unsaturated soils with the main focus being on the effects of chemical reactions. The governing equations of miscible contaminant transport including advection, dispersion-diffusion and adsorption effects together with the effect of chemical reactions are presented. The mathematical framework and the numerical implementation of the model are described in detail. The model is validated by application to a number of test cases from the literature and is then applied to the simulation of a physical model test involving transport of contaminants in a block of soil with particular reference to the effects of chemical reactions. Comparison of the results of the numerical model with the experimental results shows that the model is capable of predicting the effects of chemical reactions with very high accuracy. The importance of consideration of the effects of chemical reactions is highlighted. PMID- 17270347 TI - Dynamics of Fasciola hepatica transmission in the Andean Patagonian valleys, Argentina. AB - We described the transmission dynamics of Fasciola hepatica at its southern distribution range. Studies of prevalence and egg output in cattle and population dynamics and infection in snails were performed in a farm in the Andean Patagonian valleys, Argentina, between December 1998 and February 2002. Snail surveys were conducted from spring to autumn. Infection was diagnosed coprologically in the whole herd at the beginning and end of the study, and in a cohort of heifers at the beginning and end of 2001. A twice-a-year anthelmintic treatment was implemented in 1999. The relationship of the variables mentioned above with temperature and rainfall was determined. Lymnaea viatrix showed a life span of about 15 months and an annual pattern of population dynamics. Specimens were frequently found in temporary environments and lagoons, and rarely in streams. Snail abundance and soil-water availability were directly related in temporary environments and inversely related in lagoons. Overall prevalence in L. viatrix was 0.67% (range: 0.9-14%) and infection was detected in summer and autumn. At the beginning of the study, calves were the least infected age group (15%). Prevalences and median egg counts in grazing animals were similar at the beginning (heifers: 81%, 3.3 epg; cows: 60%, 1.3 epg) and end of the study (heifers and cows: around 51%, 1 epg). Likewise, the prevalence in the cohort of heifers remained similar (around 40%) between surveys. Transmission to cattle was highly effective despite of the short activity period and the low infection rate of snails, and the regular anthelminthic treatment. There would be two seasonal transmission peaks, one in summer-autumn, when infected snails were present, and the other in early spring due to overwintering metacercariae. Some recommendations based on the climatic conditions of the region are provided to minimize snail infection and ultimately to reduce the incidence of fasciolosis in cattle. PMID- 17270346 TI - Effects of desensitized nicotinic receptors on rotational behavior in a 6 hydroxydopamine model of Parkinson's disease. AB - The purpose of this study was to investigate the effects of desensitized nicotinic acetylcholine receptors (nAChRs) on rotational behavior in the unilateral 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). When rats were treated with different doses of nicotine, nAChRs were observed in activated, subacute desensitized, acute desensitized, and chronic desensitized states. The rotational behavior of the hemiparkinsonian rats was determined when nAChRs were in the activated or different desensitized states. The results showed that hemiparkinsonian rats exhibited no significant changes in apomorphine induced rotation when brain nAChRs were in an activated state. However, hemiparkinsonian rats displayed a significant reduction in apomorphine-induced rotational behavior when brain nAChRs were in subacute, acute, or chronic desensitized states induced by repeated administration of nicotine. When nAChRs were blocked by the nAChR antagonist mecamylamine, the behavior of the hemiparkinsonian rats worsened. These results suggest that desensitized nAChRs can lead to behavioral improvement in the 6-OHDA rat model of PD. PMID- 17270345 TI - A nitric oxide donor reduces brain injury and enhances recovery of cerebral blood flow after hypoxia-ischemia in the newborn rat. AB - Nitric oxide (NO) released in response to hypoxia-ischemia (HI) in the newborn brain may mediate both protective and pathologic responses. We sought to determine whether pharmacologic increase of NO using an NO donor would reduce neurologic injury resulting from HI in the postnatal day 7 rat. We measured NO levels and CBF in the presence of either a NOS inhibitor, N-nitro-l-arginine methyl ester (L-NAME) or an NO donor (Z)-1-[N-(2-amino-ethyl)-N-(2-ammonio ethyl)amino]diazen-1-ium-1,2-diolate (DETANONOate). Both inhibition of NOS and administration of an NO donor reduced neuropathologic injury after 7-day recovery. NO levels decreased in both ischemic and contralateral hemispheres during HI. This response was prevented by treatment with DETANONOate. Despite the decrease in NO, CBF increased during ischemia in the contralateral hemisphere but decreased when combined with brief hypoxia. Treatment with L-NAME abolished these increases, which were not altered by DETANONOate. Reduction of cellular metabolism by mild hypothermia also reduced both NO and CBF. Following prolonged HI, CBF remained decreased in the ischemic hemisphere up to 24-h recovery. This decrease was prevented by treatment with DETANONOate. These data show that administration of an NO donor reduces neurologic injury following HI in the newborn rat. This mechanism of this protection, in part, is due to an increase in the rate of recovery of CBF compared to vehicle-treated animals. Augmentation of NO-dependent increases in CBF may serve to improve neurologic outcome after perinatal asphyxia. PMID- 17270349 TI - Biophysical characterization of MDR breast cancer cell lines reveals the cytoplasm is critical in determining drug sensitivity. AB - Dielectrophoresis (DEP) was used to examine a panel of MCF-7 cell lines comprising parental MCF-7 cells and MDR derivatives: MCF-7TaxR (paclitaxel resistant, P-glycoprotein (P-gp) positive), MCF-7DoxR (doxorubicin-resistant MRP2 positive) plus MCF-7MDR1 (MDR1 transfected, P-gp positive). MCF-7DoxR and MCF 7MDR1 were broadly cross-resistant to natural product anticancer agents, whereas MCF-7TaxR cells were not, contrary to P-gp expression. Whilst DEP revealed modest membrane changes in MDR sub-lines, we saw significant changes in their cytoplasmic conductivity: MCF-7TaxR1 cigarette in the previous 30 days; mean age 16.2; 61.2% white, 6.2% Black, 17.8% Hispanic, 5.0% Asian, 3.5% other; response rate 70%) from a convenience sample of 22 Texas schools. Confirmatory factor analyses supported evidence of factorial validity for the scales in this sample. Structural equation modeling analyses suggested youth smokers have low confidence in their ability to avoid smoking, believe smoking offers emotional or social benefits, and intend to continue smoking. The scales assess smoking-related self efficacy, beliefs, and intention in this sample. Prospective studies are needed before intervention development implications are suggested. PMID- 17270358 TI - Profile of dependence symptoms among extramedical opioid analgesic users. AB - Little is known about the extent of problems due to extramedical opioid analgesic use ('analgesic misuse') in the US general population. This study explores the distribution of the seven DSM-IV-defined past-year dependence symptoms in a total household sample of 7,810 past-year extramedical opioid analgesic users using the 2002-2003 National Survey on Drug Use and Health (NSDUH). We tested for differences in opioid analgesic dependence symptom profiles across four subgroups of opioid analgesic users, different levels of deviant behaviors, and presence/absence of serious mental health problems quantified by the Composite International Diagnostic Interview Short Form (CIDI-sf). Generalized Estimated Equations (GEE) models were used to analyze the data. The most common opioid analgesic dependence symptoms were 'tolerance' (17.0%) and 'salience' (13.3%). Opioid analgesic dependence symptom profiles were 'parallel' across the groups of past-year opioid analgesic users, across deviant behavior groups and across presence/absence of serious mental health problems. Extramedical use of opioid analgesics associated with prescription drug use, having high levels of deviant behaviors, and having serious mental health problems were more strongly associated with endorsement of opioid analgesics dependence symptoms. PMID- 17270359 TI - Secondhand smoke and nicotine exposure: a brief review. AB - Secondhand tobacco smoke exposure is linked to a number of adverse health outcomes. This paper reviews published studies examining nicotine levels related to exposure to secondhand tobacco smoke. Twenty-two field studies measuring biological levels of nicotine associated with secondhand tobacco smoke exposure were evaluated. Positive associations between self-reported and/or objective measures of secondhand tobacco smoke exposure and concentrations of nicotine and/or biomarkers of nicotine in the body were frequently reported. Two studies indicated that nicotine exposure from secondhand tobacco smoke can engender plasma nicotine concentrations that are equivalent to levels produced by tobacco smoking and that are associated with nicotine-induced changes in behavior. Future research should examine whether nicotine exposure from secondhand tobacco smoke has functional effects on neurobiological and behavioral processes associated with tobacco use. PMID- 17270360 TI - Factor analysis of the Alcohol and Drug Confrontation Scale (ADCS). AB - The Alcohol and Drug Confrontation Scale (ADCS) is a 72-item instrument that defines confrontation as an individual being told "bad things" might happen if they do not make changes to address alcohol or drug problems or maintain sobriety. Preliminary assessment of the ADCS using substance abusers entering SLH's revealed: (1) scale items were frequently endorsed; (2) confrontation was often experienced as accurate and helpful; and (3) confronters' statements were viewed supportive and accurate. This study reports the results of a factor analysis on a larger sample 179 participants using baseline and 6 month follow-up data. Results yielded a clear two factor solution: (1) Internal Support (alpha=0.80) and (2) External Intensity (alpha=0.63). The two factors accounted for 58% of the variance. The ADCS offers a fresh and broader view of confrontation that can be reliably measured. PMID- 17270361 TI - Prevention of high-dose-methotrexate neurotoxicity by adequate folinic acid rescue is possible even after central nervous system irradiation. AB - Neurotoxicity, especially associated with therapy for acute lymphatic leukemia, has been attributed by many to the use of methotrexate (MTX). After radiotherapy this has been reported even more frequently but no explanation has been suggested apart from "a complex interaction". The hypothesis presented here is as follows: (1) Inadequate folinic acid rescue alone accounts for MTX-induced neurotoxicity. (2) Adequate folinic acid after MTX can prevent neurotoxicity. (3) Higher doses of MTX require a disproportionately higher dose of folinic acid than MTX to prevent toxicity. Doubling the dose of MTX has required tripling and quadrupling the folinic acid dose to prevent neurotoxicity. Assuming that central nervous system radiotherapy increases the cerebrospinal fluid levels of MTX and folinic acid proportionally, the folinic acid level may now not be enough to prevent neurotoxicity. This neurotoxicity occurs when MTX is given after (but not before) radiotherapy, and can be prevented by appropriate doses of folinic acid. (4) There is no evidence that within the dose range currently being used, the administration of larger quantities of folinic acid to prevent neurotoxicity compromises prognosis. This hypothesis is supported by a large amount of published data. Critical reanalysis of studies that ostensibly contradict parts of the hypothesis showed that they, in fact, support it. PMID- 17270362 TI - Prognostic significance of vascular endothelial growth factor expression in clear cell renal cell carcinoma. AB - The purpose of this investigation was to analyze and correlate the immunohistochemical pattern of vascular endothelial growth factor (VEGF) expression with the average of microvessel density (MVD) and other clinicopathologic parameters in clear cell renal cell carcinoma (CCRCC) in order to determine its prognostic significance. Surgical specimens of 93 CCRCC were immunohistochemically analyzed for VEGF expression, MVD with anti-CD31, and Ki 67 proliferative index. VEGF expression was recorded as the percentage of positive tumor cells (<75% and >75%) and as diffuse or perimembranous VEGF expression according to cytoplasmic distribution. Sixty-three (68%) RCC had <75% and 30 had (32%) >75% of VEGF expression. A diffuse cytoplasmic pattern of VEGF expression was found in 61(66%) RCC and a perimembranous one in 32 (34%) RCC. Statistical analysis showed that tumors with >75% of VEGF expression were characterized by lower MVD value (p=0.034), higher nuclear grade (p=0.018), and higher Ki 67 proliferation index (p=0.023). Moreover, a higher nuclear grade of tumor cells was characterized by diffuse cytoplasmic VEGF distribution (p=0.005). This tumor model did not confirm the postulated simple relationship between VEGF overexpression and angiogenesis through high microvessel count. However, the study results indicated that overexpression of VEGF was a worse histologic prognostic parameter in CCRCC. PMID- 17270364 TI - Validating the significance of genomic properties of Chi sites from the distribution of all octamers in Escherichia coli. AB - Chi sites (5'-GCTGGTGG-3') are homologous recombinational hotspot octamer sequences, which attenuate the exonuclease activity of RecBCD in Escherichia coli. They are overrepresented in the genome (1008 occurrences), preferentially located within coding regions (98%), oriented in the direction of replication (75%), and occur most commonly on the mRNA-synonymous sense strand of the double helix (79%). Previous statistical studies of the genome sequence suggested that these genomic properties of Chi sites appear to be related to their role in recombinational repair and therefore to replication and transcription. In this study, we employ three mathematical models to predict the properties of Chi sites from single nucleotide and multi-nucleotide compositions, and validate them statistically using the distribution of all octamer sequences in the entire genome, or exclusively within ORFs. The model based on the overall distribution of all octamers provided better predictions than the single nucleotide composition model, and the ORF and sense strand preference of Chi sites were shown to be within the standard deviation of all octamers. In contrast, the orientation bias of the Chi sites in the direction of replication was significant, although the bias was not as pronounced as with the single nucleotide composition model, suggesting a selective pressure related to the role of RecBCD in replication. PMID- 17270363 TI - Splice variants and expression patterns of SHEP1, BCAR3 and NSP1, a gene family involved in integrin and receptor tyrosine kinase signaling. AB - SHEP1, BCAR3 and NSP1 are the three members of a family of cytoplasmic proteins involved in cell adhesion/migration and antiestrogen resistance. All three proteins contain an SH2 domain and an exchange factor-like domain that binds both Ras GTPases and the scaffolding protein Cas. SHEP1, BCAR3 and NSP1 mRNAs are widely expressed in tissues, and SHEP1 and BCAR3 have multiple splice variants that differ in their 5' untranslated regions and in some cases the beginning of their coding regions. Interestingly, our data suggest that SHEP1 is highly expressed in blood vessels in mouse breast cancer models. In contrast, BCAR3 and NSP1 are more highly expressed than SHEP1 in breast cancer cells. These expression patterns suggest differential roles for the three genes during breast cancer progression in either the vasculature or the tumor cells. PMID- 17270365 TI - Occurrence, species distribution, antimicrobial resistance and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of domestic animals. AB - beta-Lactams and macrolides are important antibiotics for treatment of staphylococcal infections in both humans and animals. The aim of the study was to investigate the occurrence, species distribution and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of dogs, horses, pigs, and cattle in Denmark. Nasal swabs were collected from a total of 400 animals, including 100 individuals of each species. Methicillin- and erythromycin resistant staphylococci were isolated on selective media, identified by 16S rDNA sequencing, and typed by pulsed field gel electrophoresis (PFGE). Methicillin resistant coagulase-negative staphylococci (MRCoNS) harbouring mecA were isolated from horses (50%) and dogs (13%), but not from food animals. The species identified were S. haemolyticus (n=21), S. vitulinus (n=19), S. sciuri (n=13), S. epidermidis (n=8), and S. warneri (n=2). mecA-mediated methicillin resistance in S. vitulinus was described for the first time. Methicillin-resistant S. aureus was not detected. PFGE analysis revealed the presence of specific MRCoNS clones in samples originating from the same veterinary hospital or equine farm. Erythromycin-resistant S. aureus (ERSA) was detected in 38% of pigs and all isolates harboured a constitutively expressed erm(C) gene. The vast majority (37/38) of pigs carrying ERSA originated from a farm characterized by frequent use of macrolides. Most ERSA isolates (28/38) displayed indistinguishable or closely related PFGE patterns, indicating clonal distribution within the farm. Based on the analysis of data on antimicrobial consumption, the occurrence of MRCoNS in companion animals and that of ERSA in pigs reflected national and local patterns of antimicrobial usage. PMID- 17270366 TI - Association of hepatitis E virus (HEV) and postweaning multisystemic wasting syndrome (PMWS) with lesions of hepatitis in pigs. AB - The aim of the study was to determine the presence of swine hepatitis E virus (HEV) RNA and antibodies in postweaning multisystemic wasting syndrome-affected (n=114) and non-affected (n=46) pigs and the possible association with hepatitis lesions. Forty-four pigs were RT-PCR positive (28.2%); 25 of them were PMWS cases, while 19 were non-PMWS pigs. In both groups, HEV RT-PCR results were associated with hepatitis (OR=5.61 for PMWS-affected pigs and OR=5.17 for non PMWS affected pigs; p=0.01). No interaction was detected in a logistic regression between PMWS occurrence and HEV infection for the development of hepatitis lesions. Seropositivity to HEV was more likely to occur in pigs with hepatitis (51.9%) compared to pigs without hepatitis (36.1%; p=0.03). Significant differences in optical densities were notices comparing the lesional stage of pigs (p=0.009). While pigs with slight or moderate hepatitis were seropositive, pigs with more severe lesions were seronegative to HEV. These results indicate that swine HEV infection can be a significant contributor to the development of moderate hepatitis in pigs regardless of the PMWS status. PMID- 17270367 TI - Production of superoxide anion and hydrogen peroxide by capacitating buffalo (Bubalus bubalis) spermatozoa. AB - In the present study attempts were made to detect and quantify the generation of superoxide anion (O(2)(*-)) and hydrogen peroxide (H(2)O(2)) by capacitating buffalo spermatozoa. Ejaculated buffalo spermatozoa were suspended in sp-TALP medium at 50x10(6)mL(-1) and incubated at 38.5 degrees C with 5% CO(2) in air in the absence or presence of heparin (a capacitation inducer) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) or diphenyleneiodonium (DPI, a flavoprotein inhibitor) for 6h. Production rate of O(2)(*-) and H(2)O(2) by spermatozoa at different hours of capacitation were measured by cytochrome c reduction and phenol red oxidation assays, respectively. Spermatozoa generated both O(2)(*-) and H(2)O(2) spontaneously and following stimulation with heparin and a significant increase of O(2)(*-) production was observed in the presence of NADPH. However, DPI inhibited this NADPH-induced O(2)(*-) production and suggested for existence of putative NADPH-oxidase that constitute a specific O(2)(*-) generating systems in buffalo spermatozoa. Results of our study indicated that buffalo spermatozoa generate O(2)(*-) and H(2)O(2) and production of these free radicals is induced during capacitation. PMID- 17270369 TI - Sire effect on the pregnancy outcome in beef cows synchronized with progesterone based Ovsynch and CO-Synch protocols. AB - The objective was to determine the sire effect on the pregnancy outcome in beef cows in which stage of estrus was synchronized with progesterone based fixed-time artificial insemination (AI) protocols. Three Angus sires with more than 300 breedings were evaluated for differences in pregnancy outcome from 1868 inseminations. Angus cross beef cows (N=1868) were synchronized with Ovsynch-CIDR or CO-Synch-CIDR protocols for fixed-time AI. Cows in both groups that showed estrus on day 9 before 1500 h were designated to Selectsynch-CIDR group and were inseminated according to AM-PM rule. Results indicated that Sire 2 had lower fixed-time AI pregnancy rate compared to Sire 3 (48.1% versus 58.7%; P=0.01). Significant sirexsynchronization program and sirexlocation interactions were observed for fixed-time AI (P<0.05). Sire 2 had a lesser fixed-time AI pregnancy in both Ovsynch-CIDR and CO-Synch-CIDR groups compared to Sire 3. In two of four locations, Sire 2 had a lesser fixed-time pregnancy rate compared to Sire 3. No sire differences were observed in AI pregnancy for cows in Selectsynch-CIDR group. In conclusion, evidence in this study suggest that there are differences in sire fertility when they were used in fixed-time AI protocols, possibly due to the sire differences in sperm capacitation process. Further studies are needed to investigate association of the sire differences in fixed-time AI protocols with sire differences in the sperm capacitation process. PMID- 17270368 TI - Luteotrophic effect, growth and survival of whole versus half embryos and, their relationship with plasma progesterone concentrations of recipient dairy heifers. AB - This prospective and randomised experiment was designed to compare the luteotrophic effect of whole versus half embryos and, to evaluate the relationship between the plasma progesterone (P4) profiles and the rates of early embryonic (from Days 7 to 25), late embryonic (Days 25-42) and foetal (Days 42 63) mortalities of whole and half embryo recipients. Within a single herd, 188 virgin, healthy, cyclic, reproductively sound, with adequate body condition score, Holstein dairy heifers were randomly allocated to receive one whole or one half embryo on Day 7 of the oestrous cycle (Day 0=estrus). In each embryo transfer (ET) group, half of the recipients were treated with a CIDR (controlled internal drug releasing device) between Days 7 and 19. Pregnancy was evaluated by ultrasound on Days 25, 42 and 63 and plasma P4 profiles were obtained until Day 63 of pregnancy. CIDR-treated and untreated heifers had similar pregnancy rates on Days 25, 42 and 63 and, embryo size on Day 42 was also similar in treated and untreated recipients. Therefore, CIDR treatment failed to promote growth and survival of half and whole embryos. Half embryos presented a significantly higher rate of early and late embryonic mortality than whole embryos. In contrast, foetal mortality was similar in whole and half embryos and, this was coincidental to a similar embryo size on Day 42. Therefore, half embryos exhibited a compensatory growth until Day 42, irrespective of CIDR treatment, after which they presented a similar survival rate to that of whole embryos. Half embryo derived pregnancies presented significantly lower plasma P4 concentrations on Day 25 than whole embryo-derived pregnancies, suggesting that this lower luteotrophic effect of half embryos could be related to their higher rate of late embryonic mortality. No significant relationship between the early luteal P4 concentrations and embryo survival was observed in whole and half embryo recipients. The first detectable luteotrophic effect of embryonic origin was observed on Day 14 and no detectable second luteotrophic effect was observed until Day 63 of pregnancy. Treatment with CIDR significantly increased plasma P4 concentrations during treatment but induced a significant decrease after removal of the device, suggesting that secretion of luteotropins was downregulated in the course of treatment. PMID- 17270370 TI - Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. AB - OBJECTIVES: Levonorgestrel (LNG), delivered locally into the uterine cavity has a profound effect on the endometrium. The aim of the study was to use a LNG intrauterine system to treat non-atypical and atypical endometrial hyperplasia in women and to evaluate the long-term cure (remission) rate. METHODS: Each of the 20 women in the study, of whom eight were diagnosed with atypical hyperplasia, received a LNG-IUS, releasing 20 microg LNG/day. The study is a non-comparative study with long-term follow-up (range 14-90 months). RESULTS: All women developed a normal endometrium, except one asymptomatic woman with atypical hyperplasia who still had focal residual non-atypical hyperplasia at 3 years follow-up in the presence of a thin (< 4 mm) endometrium. CONCLUSION: Continuous intrauterine delivery of LNG appears to be a promising alternative to hysterectomy for the treatment of endometrial hyperplasia and could enhance the success rate when compared with other routes of progestagen administration as well as intrauterine progesterone delivery. The significant reduction of the PR expression observed during treatment with the LNG-IUS appears to be a marker for the strong antiproliferative effect of the hormone at a cellular level resulting in an inhibition of estrogen bioactivity and endometrial suppression. PMID- 17270371 TI - Possible inhibitory mechanism of Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated Caco-2 cells. AB - Curcuma longa and C. zedoaria, belonging to genus Curcuma, have become prevalent as supplements in East Asia. Curcumin is the most well-studied bioactive component isolated from rhizomes of C. longa and other Curcuma species except C. zedoaria. In this study, we investigated the affects of C. longa, C. zedoaria from Japan and curcumin on CYP3A4. Caco-2 cells, in which CYP3A4 expression was induced by 1alpha,25-(OH)(2)-D(3), were used to mimic the metabolism of small intestine. Caco-2 cells were treated with methanol extracts from two Curcuma rhizomes (0.1mg/ml) or curcumin (30 microM) for 72 h. Both extracts significantly decreased the activity of CYP3A4 by about 85-98%. The 50% inhibitory concentrations of C. longa and C. zedoaria extracts were 0.019 and 0.014 mg/ml, respectively. They caused a 60-70% decrease in CYP3A4 protein. Otherwise, curcumin treatment caused a 30-40% decrease in CYP3A4 catalytic activity and a 38% decrease in CYP3A4 protein expression. Moreover, it was found that both Curcuma extracts and curcumin treatment had no influence on CYP3A4 mRNA expression. Our results suggested that administration of Curcuma drugs might inhibit the catalytic activity of intestinal CYP3A4. However, curcumin was not the major compound responsible for this inhibitory effect. PMID- 17270373 TI - Effect of fiber length of carbon nanotubes on the absorption of erythropoietin from rat small intestine. AB - Erythropoietin (EPO) loaded carbon nanotubes (CNTs) with surfactant as an absorption enhancer were prepared for the oral delivery of EPO using two types of CNTs, long and short fiber length CNTs, and the effect of CNT fiber length on the absorption efficiency of EPO was studied. After Labrasol, PEG-8 caprylic/capric glycerides, as absorption enhancer was adsorbed into long fiber CNTs of which mean fiber length was 20-80 microm, as a carrier, EPO and casein as protease inhibitor and Explotab (sodium starch glycolate) as a disintegrating agent, were mixed. The resulting solid preparation was administered into the rat jejunum and serum EPO levels were measured by ELISA. The dose of EPO, CNTs, casein and Explotab were 100 IU/kg, 5mg/kg, 25mg/kg and 2.5mg/kg, respectively. Serum EPO level reached to C(max), 69.0+/-3.9 mIU/ml, at 3.5+/-0.1h and AUC was 175.7+/ 13.8 mIU h/ml. These values were approximately half of that obtained with short fiber length CNTs of which C(max) was 143.1+/-15.2 mIU/ml and AUC was 256.3+/-9.7 mIU h/ml. When amphoteric surfactant, Lipomin LA, sodium beta-alkylaminopropionic acid, was used to accelerate the disaggregation of long fiber length CNTs, C(max) was 36.0+/-4.9 and AUC was 96.9+/-11.9, which showed less bioavailability (BA) of EPO. These results suggest that the short fiber length CNTs deliver more both EPO and absorption enhancer to the absorptive cells of the rat small intestine and the aggregation of CNTs is not the critical factor for the oral delivery of EPO. PMID- 17270374 TI - Simultaneous cancellation of air and bone conduction tones at two frequencies: extension of the famous experiment by von Bekesy. AB - Cancellation experiments between air conduction (AC) and bone conduction (BC) tones were conducted at two frequencies (0.7 and 1.1 kHz) and three levels (40, 50, and 60 dB HL) in three subjects. The tests were divided into three categories: (1) single tone cancellation, (2) simultaneous cancellation of two tones, and (3) cancellation of one tone while a disturbing tone was present. In total, each subject performed twelve cancellation tasks. The hypothesis is that the AC and BC sound transmission behaves as linear systems and they both excite the basilar membrane in the cochlea similarly. The cancellation results are presented as the deviations from this hypothesis; except for a few larger deviations, the intrasubject deviations were generally less than 0.5 dB and 5 degrees. The results from all three test categories indicate that the hypothesis of linear transmission systems and similarity of cochlear stimulation by AC and BC holds. However, due to the subjects' limited ability to conduct optimal cancellation and to imperfect methodology and equipment, the small deviations from perfectly linear cancellation that were observed do neither conclusively prove nor refute the possibility of small differences in the cochlear processing of AC and BC sound. Nonetheless, it is clear that if such differences in the processing of the two stimuli exist, they are small in magnitude. PMID- 17270372 TI - Role of copper gluconate/triethanolamine in irinotecan encapsulation inside the liposomes. AB - A novel method for encapsulating irinotecan into liposomes containing copper gluconate buffered to pH 7.0 with triethanolamine (TEA) has recently been developed. In the present study, the mechanism dictating drug encapsulation and retention inside those liposomes was investigated. Spectroscopic analyses revealed that irinotecan interacted with copper gluconate/TEA in solution. Fourier transformed infrared (FT-IR) spectroscopy indicated a strengthening of the hydrogen bonds involving the hydroxyl groups when solutions of irinotecan and copper gluconate/TEA are mixed at a 1:1 molar ratio. The intensity of the circular dichroism (CD) signal of copper gluconate/TEA increased in the presence of equimolar amounts of irinotecan. The addition of irinotecan to liposomes containing copper gluconate/TEA at 50 degrees C induced a shift of the absorption bands from 370 nm to 378 nm as well as a 60% quenching of the drug fluorescence at 440 nm suggesting the occurrence of irinotecan self association. Irinotecan encapsulation was found to be kinetically and stoichiometrically correlated with the release of TEA from the liposomes. The results suggested that the encapsulation of irinotecan was mediated by TEA in association with copper gluconate, leading to a final drug complex that is retained inside the liposomes. A neutral antiport exchange loading mechanism between irinotecan and TEA is proposed. PMID- 17270375 TI - The influence of externalization and spatial cues on the generation of auditory brainstem responses and middle latency responses. AB - The effect of externalization and spatial cues on the generation of auditory brainstem responses (ABRs) and middle latency responses (MLRs) was investigated in this study. Most previous evoked potential studies used click stimuli with variations of interaural time (ITDs) and interaural level differences (ILDs) which merely led to a lateralization of sound inside the subject's head. In contrast, in the present study potentials were elicited by a virtual acoustics stimulus paradigm with 'natural' spatial cues and compared to responses to a diotic, non-externalized reference stimulus. Spatial sound directions were situated on the horizontal plane (corresponding to variations in ITD, ILD, and spectral cues) or the midsagittal plane (variation of spectral cues only). An optimized chirp was used which had proven to be advantageous over the click since it compensates for basilar membrane dispersion. ABRs and MLRs were recorded from 32 scalp electrodes and both binaural potentials (B) and binaural difference potentials (BD, i.e., the difference between binaural and summed monaural responses) were investigated. The amplitudes of B and BD to spatial stimuli were not higher than those to the diotic reference. ABR amplitudes decreased and latencies increased with increasing laterality of the sound source. A rotating dipole source exhibited characteristic patterns in dependence on the stimulus laterality. For the MLR data, stimulus laterality was reflected in the latency of component N(a). In addition, dipole source analysis revealed a systematic magnitude increase for the dipole contralateral to the azimuthal position of the sound source. For the variation of elevation, the right dipole source showed a stronger activation for stimuli away from the horizontal plane. The results indicate that at the level of the brainstem and primary auditory cortex binaural interaction is mostly affected by interaural cues (ITD, ILD). Potentials evoked by stimuli with natural combinations of ITD, ILD, and spectral cues were not larger than those elicited by diotic chirps. PMID- 17270376 TI - US diagnosis of cervical recurrence in patients operated on thyroid cancer: sonographic features and clinical significance. AB - OBJECTIVE: To describe the sonographic features of cervical recurrence in patient with thyroid cancer and review clinical significance. MATERIALS AND METHODS: Twenty-two consecutive patients with 24 surgically confirmed recurrences undergoing preoperative ultrasonography (US) and US-guided fine needle aspiration biopsy (FNAB) were enrolled. Retrospective analysis was conducted on the sonographic features of recurrence including size, location, shape, echogenicity, multiplicity, laterality relative to initial primary tumor and presence of characteristic findings; cystic change and microcalcification. In addition, review was made on their clinical data including the time interval between the thyroidectomy and the recurrence, serum thyroglobulin (Tg), anti-thyroglobulin antibody (Tg Ab) and 131 iodine whole body scan (IWBS). RESULTS: Fifteen of 24 recurrences occurred in internal jugular lymphatic chain and 9 in the postoperative paratracheal region with mostly ipsilaterally to the initial tumor (19/24). Their mean size was 1.0 cm (range: 0.5-2.5 cm) with ovoid (n=18) or lobulated (n=6) shape. They appeared hyperechoic in nine (37.5%), hypoechoic in nine (37.5%), and mixed echoic due to cystic change in six (25.0%). Microcalcification was observed in eight (33.3%) and multiplicity in seven (29.2%). US-guided FNAB established the preoperative diagnosis of recurrence in all. The mean interval between the thyroidectomy and recurrence was 59 months (range: 15-162 months). Suspicion of recurrence was possible in 8 with Tg of 2 ng/ml or greater (8/24) during thyroxine (T4) therapy and 6 (6/8) after T4 withdrawal. All of the 8 recurrences were negative on 131 IWBS. In two patients with Tg less than 2 ng/ml after T4 withdrawal, elevated Tg Ab was observed. CONCLUSION: US and US-guided FNAB are valuable postoperative follow up modalities of thyroid cancer due to their convenience, early detection and precise localization. Therefore, it's essential to get familiar with sonographic findings of cervical recurrence. PMID- 17270377 TI - Post-surgical meningitis due to multiresistant Acinetobacter baumannii. Effective treatment with intravenous and/or intraventricular colistin and therapeutic dilemmas. AB - Post-surgical meningitis and/or ventriculitis caused by Gram-negative bacteria may be difficult to treat due to the emergence of multiresistant strains. Two patients with multiresistant Acinetobacter baumannii central nervous system infection, successfully treated with either intravenous and/or intraventricular colistin are presented. Unresolved issues such as dose and duration of intraventricular colistin are discussed. PMID- 17270378 TI - [Syphilis hepatitis and liver transplantation]. AB - We report a case of secondary syphilis hepatitis in a liver-transplant patient. This homosexual male patient presented, 15 years after orthotopic liver transplantation, with non-squamous papulomacular rash, mild cytolysis, and anicteric cholestasis. Laboratory tests showed syphilis seroconversion with a venereal diseases research laboratory (VDRL) titer of 1/256, a Treponema pallidum hemaglutination assay (TPHA) of 1/5120, and a positive IgM fluorescent Treponemal antibody absorbance (FTA-abs). A liver biopsy performed 13 months after the diagnosis showed low-grade hepatitis with a Metavir score of A1F1; it also showed non-specific portal moderate inflammation consisting primarily of neutrophils, with no evidence of cholestasis. He was given benzathine-penicillin at 2,400,000 IU with a transient increase in prednisolone doses. Cytolysis rapidly, and cholestasis progressively disappeared. IgM FTA-abs became negative, whereas VDRL and TPHA titers decreased slightly over time. PMID- 17270380 TI - Analysis of carvedilol in human plasma using hydrophilic interaction liquid chromatography with tandem mass spectrometry. AB - A rapid, sensitive and selective method for the determination of carvedilol in human plasma was developed using hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS). Carvedilol and cisapride (internal standard) were extracted from human plasma with methyl tert-butyl ether at basic pH and analyzed on an Atlantis HILIC Silica column with the mobile phase of acetonitrile-ammonium formate (50 mM, pH 4.5) (90:10, v/v). The analytes were detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r=0.9998) over the concentration range of 0.1-200 ng/ml. The lower limit of quantification for carvedilol was 0.1 ng/ml using 50 microl plasma sample. The coefficient of variation and relative error for intra- and inter-assay at four QC levels were 1.6-4.5% and -6.4 to 4.8%, respectively. The absolute and relative matrix effect for carvedilol and cisapride were practically absent. The extraction recoveries of carvedilol and cisapride were 81.6 and 85.2%, respectively. This method was successfully applied to the bioequivalence study of carvedilol in humans. PMID- 17270381 TI - [Anaesthetic management of oesophagectomy: advances and perspectives]. AB - Oesophagectomy is still characterized by a high postoperative mortality and respiratory morbidity. Nevertheless, epidemiological, medical and surgical advances have improved the management of this surgical procedure. The anaesthesiologist influence is present at each level, from the preoperative evaluation to the management of postoperative complications. The preoperative period is improved by the use of assessment scores, the better knowing of respiratory risk factors and of the neoadjuvant therapy adverse effects. The main objective of the operative period is to ensure a rapid weaning procedure and stability of the respiratory and haemodynamic functions, warranting the anastomotic healing. The interest of the association between respiratory rehabilitation and thoracic epidural analgesia is highlighted in the postoperative period. The management of postoperative complications, mainly represented by respiratory failure and anastomotic leakages, requires a multidisciplinary analysis. The potential interest of non-invasive ventilation and of the modulation of postoperative inflammatory response needs further investigation. PMID- 17270379 TI - Automated approach to couple solubility with final pH and crystallinity for pharmaceutical discovery compounds. AB - The design and validation of a novel high-throughput system for thermodynamic solubility determination requiring only 5 mg of sample is described. The system uses a sintered nickel filter assembly to recover excess solids from saturated solutions for rapid crystallinity assessment via powder X-ray diffraction (PXRD). Moreover, the system measures the pH of filtrates to provide a final pH value with the solubility measurement. The limit of detection for the UV-vis plate reader used on this system is approximately 0.001 mg/ml, while the practical upper limit is approximately 3 mg/mL. The solubility measurements of 60 proprietary Pfizer compounds were used to validate the nickel filter assembly against a more conventional polyvinylidenedifluoride (PVDF) filter. Additionally, a comparison was made between a subset of 10 compounds run on the automated system and a more traditional shake-flask method employing HPLC analysis. In both cases, a favorable comparison was obtained. PMID- 17270382 TI - Liposomes modify the subcellular distribution of sclareol uptake by HCT-116 cancer cell lines. AB - The uptake of free and liposome-incorporated sclareol and its effect on the growth of human cancer cell line HCT-116 was investigated. Recovery of free and liposomal sclareol in cytosol, nuclei and crude membranes was monitored over time. HCT-116 cells were incubated with 100 microM of free or liposomal sclareol up to 96 h. Intact cells were subjected to subcellular fractionation in order to obtain highly purified fractions of nuclei, cytosol, and crude membranes. Sclareol was extracted from intact cells and from the subcellular fractions using the Bligh-Dyer method and was measured by HPTLC/FID. The effect of sclareol on cell growth was found time dependent. Free sclareol exhibited high toxicity, while the liposomal sclareol showed reduced cytotoxicity but retained the ability to reduce the cell growth rate. The uptake of sclareol by the cells was faster and higher compared to that of its liposomal form. The concentration of sclareol in the three subcellular fractions showed that liposomal sclareol is incorporated in crude membranes and from there it is released in cytosol and nuclei in a time dependent manner, while free sclareol passes directly in the cytosol. These results suggest that liposomal sclareol retains its growth inhibiting activity while its cytotoxic action is diminished. These findings could be due to the sustained delivery of sclareol to the different subcellular sites. PMID- 17270383 TI - Influence of nutritional status on serum large N-truncated PTH, but not PTH(1-84) in hemodialysis patients. AB - BACKGROUND: Serum level of parathyroid hormone (PTH), measured by second generation intact PTH (I-PTH), is known to be associated with nutritional status in hemodialysis (HD) patients. We investigated whether PTH(7-84) and larger N truncated PTH or PTH(1-84) might be affected by nutritional status in HD patients. METHODS: Serum PTH was determined in 170 male HD patients by either a Bio-intact PTH (Bio-PTH) or I-PTH assay. Lean body mass in the trunk region was measured as a nutritional marker by dual X-ray absorptiometry. RESULTS: The serum PTH(7-84) level was theoretically obtained from the difference between serum I PTH and Bio-PTH because I-PTH assay cross-reacted with PTH(7-84) with the same degree as PTH(1-84), although N-truncated PTH fragment larger than PTH(7-84) might affect theoretical serum PTH(7-84) level, although slightly. Serum PTH(1 84) was directly obtained from the serum Bio-PTH value because of its exclusive reaction with PTH(1-84). Serum PTH(7-84) correlated significantly with nutritional markers such as body weight, albumin, protein catabolic rate (PCR), TACBUN, BUN, phosphate, and lean body mass in the trunk, whereas PTH(1-84) correlated only with phosphate. Multiple regression analysis revealed that PCR, body weight, and lean body mass in the trunk region are significant factors independently associated with PTH(7-84), but not with PTH(1-84). CONCLUSIONS: The results suggest that serum levels of PTH(7-84) and larger N-truncated PTH fragments, but not PTH(1-84), might be affected by the nutritional state in HD patients, which might explain the reported correlation of serum I-PTH levels with nutritional markers. PMID- 17270384 TI - [Do observational studies have a role in assessing treatment?]. AB - Case-control and cohort studies are the two principal types of observational studies. Case-control studies compare a group of patients with a given disease and a group of subjects without it (controls). An association between the risk factor tested (which may be a drug) and the disease is assessed by comparing the frequency of exposure to this risk factor in each group. In a cohort study, a large group of subjects initially free from the disease is followed over time. Exposure is assessed at the beginning of the study. The risk factor is associated with the disease if the incidence of the disease during follow-up is higher among exposed than non-exposed subjects. Associations observed in observational studies cannot be considered causal, in contrast to those in randomized controlled trials. Observational studies generate hypotheses that must be formally tested in randomized trials, even when all the elements supporting causality (dose-effect relation, biological plausibility, strength and independence of the association) are present. In trials, randomization, blinding and intention-to-treat analysis allow assessment of initial and secondary comparability between the two groups, so that any difference between the two groups can be attributed to the intervention or agent tested. PMID- 17270385 TI - [Two thirds of patients with gastroesophageal reflux have nocturnal symptoms: survey by 562 general practitioners of 36,663 patients]. AB - OBJECTIVE: Gastroesophageal reflux disease (GERD) affects about 10% of the French population, who have symptoms at least weekly. Nocturnal symptoms are associated with more severe disease. The aim of this study was to determine the prevalence of nocturnal reflux symptoms among patients seeing general practitioners and to assess their consequences on sleep quality. METHODS: For three consecutive days, 562 general practitioners identified among all the adult patients they saw those with GERD symptoms (heartburn or regurgitation) in the previous 3 months and characterized the symptoms. RESULTS: Prevalence of GERD among the 36663 consulting patients was 8.3%, and 64.6% of them (that is, 5.4% of the general population) reported nocturnal GERD. Patients with nocturnal symptoms did not differ from those with only diurnal symptoms except smokers had a significantly higher rate of nocturnal than diurnal symptoms (28 versus 23%, p=0.0053). GERD symptoms were related to nocturnal awakening in 58.6% of patients, were present in the early morning for 41.6% and in the evening at bedtime for 39.5%. Nocturnal awakening, difficulty in falling asleep and nightmares occurred significantly more frequently in patients with nocturnal symptoms (respectively 56 versus 24%; 41 versus 31%; 14 versus 9%). Likewise, atypical nondigestive symptoms occurred significantly more frequently in patients with nocturnal symptoms (74 versus 51%, p<0.0001). Quality of sleep was considered "poor or very poor" more frequently in patients with nocturnal symptoms (58 versus 34%, p<0.0001). CONCLUSION: Approximately 2/3 of GERD patients have nocturnal symptoms that appear to have a significant negative impact on sleep and well-being. These results show the need to evaluate specific therapeutic approaches to reduce sleep disturbances in these patients. PMID- 17270386 TI - [Evaluation of drug efficacy]. AB - The therapeutic value of drugs is currently assessed by the "commission de la transparence" (transparency committee), which since January 2005 has reported to the Haute autorite de sante (high health authority). After a drug is authorized for sale, this committee evaluates its therapeutic value, or more precisely, interest, taking into account other drugs already on the market to treat the same disease and the position of the drug expected in the overall therapeutic strategy of the concerned disease. The committee uses scientific methodology to determine the level of "expected medical service" and also evaluates the advantages that the new drug instead of this drug is expected to provide compared with other drugs for the same indication. The public health contribution of the drug is one of the criteria considered. A new methodology and clarification of its definition make it possible to assess this with precision. Quantification of these criteria results in a score for the drug that determines whether or not it will be reimbursed by the national health insurance fund. This score also helps the drug economics committee determine a price for the drug (improvement of the expected medical service). PMID- 17270387 TI - REMOVED: Inhibition of doxorubicin-induced clastogenic effect by Aegle marmelos (L.) correa in cultured V79 cells. AB - This article has been removed consistent with Elsevier Policy on Article Withdrawal. Please see http://www.elsevier.com/locate/withdrawalpolicy. The Publisher apologies for any inconvenience this may cause. PMID- 17270388 TI - Assessing anxiety with the Child Behavior Checklist and the Teacher Report Form. AB - We evaluated the utility of Anxiety scales for the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). The scales (CBCL-A; TRF-A) were examined using mothers and teachers of anxiety-disordered (AD; 157 mothers, 70 teachers) and non-anxiety-disordered (NAD; 100 mothers, 17 teachers) children. Separate samples of parents and teachers of AD (mothers=145, fathers=120, teachers=137) and NAD (mothers=35, fathers=29, teachers=27) children cross validated the original findings. CBCL-A and TRF-A scores significantly discriminated AD children from NAD children and correlated significantly with other measures of child anxiety. The CBCL-A and TRF-A were sensitive to treatment changes. Relative to the CBCL/TRF Anxious/Depressed syndromes and Internalizing dimensions, the CBCL-A and TRF-A improved prediction of anxiety status. Relative to Achenbach, Demenci, and Rescorla's [Achenbach, T. M., Demenci, L., & Rescorla, L. A. (2003). DSM-oriented and empirically based approaches to constructing scales from the same item pools. Journal of Clinical Child and Adolescent Psychology, 32, 328-340] CBCL Anxiety subscale, the CBCL-A predicted comparably. Findings are discussed in terms of the CBCL-A and TRF-A as clinical tools. PMID- 17270389 TI - Posttraumatic stress disorder symptoms in trauma-exposed college students: the role of trauma-related cognitions, gender, and negative affect. AB - Considerable evidence indicates a prominent role for trauma-related cognitions in the development and maintenance of posttraumatic stress disorder (PTSD) symptoms. The present study utilized regression analysis to examine the unique relationships between various trauma-related cognitions and PTSD symptoms after controlling for gender and measures of general affective distress in a large sample of trauma-exposed college students. In terms of trauma-related cognitions, only negative cognitions about the self were related to PTSD symptom severity. Gender and anxiety symptoms were also related to PTSD symptom severity. Theoretical implications of the results are discussed. PMID- 17270390 TI - Is juvenile psychopathy associated with low anxiety and fear in conduct disordered male offenders? AB - Although the traditional conceptualization of psychopathy suggests that this construct is negatively associated with anxiety the literature has produced mixed findings. The present study examined the relationship between self-report measures of anxiety/fear and psychopathy assessed using the Psychopathy Checklist: Youth Version in 110 adolescent male offenders with conduct disorder. In line with the literature in children, we found that measures of anxiety and fearfulness exhibited differential associations with different elements of psychopathy. Specifically, we found that trait anxiety was negatively correlated with the affective components of the psychopathy construct and that fearfulness was negatively correlated with the more antisocial components of the construct. The findings are discussed in the context of growing literature on psychopathy assessment in younger cohorts. PMID- 17270391 TI - Pathological worry, anxiety disorders and the impact of co-occurrence with depressive and other anxiety disorders. AB - The Penn State Worry Questionnaire (PSWQ) was administered to 123 outpatients with principal diagnoses of generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder with agoraphobia, and panic disorder without agoraphobia (PD) to examine the specificity of pathological worry for GAD. The mean PSWQ scores in patients with GAD and SAD were significantly higher than the mean PSWQ scores in patients with PD, while not differing significantly in the subgroups without any co-occurring depressive or anxiety disorders. Patients with any co-occurring depressive or anxiety disorder scored significantly higher on the PSWQ. In a logistic regression analysis, high PSWQ scores independently predicted only GAD and SAD diagnoses. The study suggests that pathological worry is specific not only for GAD, and indicates that a significant relationship exists between pathological worry, GAD and SAD, and that depressive and anxiety disorders co-occurrence increases levels of pathological worry in patients with anxiety disorders. PMID- 17270392 TI - Efficacy of interoceptive exposure therapy combined with trauma-related exposure therapy for posttraumatic stress disorder: a pilot study. AB - The aim of this case series was to examine efficacy of interoceptive exposure (IE) combined with trauma-related exposure therapy (TRE) for posttraumatic stress disorder (PTSD). Seven participants completed treatment consisting of four weekly sessions of IE followed by eight weekly sessions of TRE (four sessions of imaginal exposure and four sessions of in vivo exposure). Assessments were conducted at pretreatment, posttreatment, 1- and 3-month follow-up. Outcome measures included PTSD symptoms, anxiety sensitivity, posttraumatic cognitions, anxiety, and depression. Five of the seven participants showed pre- to posttreatment improvements on these measures, and two participants showed less symptom reduction. Results at the 1-month follow-up showed that treatment gains were generally maintained in five (of the seven) participants and four of these individuals no longer met PTSD diagnostic criteria. Four individuals completed the 3-month follow-up and their symptoms and diagnostic status remained unchanged. These preliminary findings are promising. The next step in this line of research is to conduct a randomized, controlled trial to further to examine the efficacy, tolerability, and mechanisms of using IE in the treatment of PTSD. PMID- 17270393 TI - Generalized anxiety disorder and entry into marriage or a marriage-like relationship. AB - Previous studies have suggested that individuals with generalized anxiety disorder report significantly higher levels of marital distress and are at a greater risk for divorce than those without generalized anxiety disorder. Studies also showed that relationship difficulties among those with generalized anxiety disorder predict poor treatment response and long-term outcome. In this study, the relation between a lifetime diagnosis of generalized anxiety disorder and marital history was examined with the data from the National Comorbidity Survey (NCS). Respondents were grouped into those who have no mental disorder, those who have only generalized anxiety disorder, and those who have generalized anxiety disorder and a lifetime history of at least one of the 16 DSM-III-R diagnoses assessed in the NCS. Generalized anxiety disorder was significantly associated with the likelihood of entry into a marriage-like relationship. The results support the continued investigation into the association between couple functioning and the onset, course, and treatment of generalized anxiety disorder, and suggest that couples intervention could be an untapped resource for generalized anxiety disorder treatment. PMID- 17270394 TI - A BAC-based physical map of the apple genome. AB - Genome-wide physical mapping is an essential step toward investigating the genetic basis of complex traits as well as pursuing genomics research of virtually all plant and animal species. We have constructed a physical map of the apple genome from a total of 74,281 BAC clones representing approximately 10.5x haploid genome equivalents. The physical map consists of 2702 contigs, and it is estimated to span approximately 927 Mb in physical length. The reliability of contig assembly was evaluated by several methods, including assembling contigs using variable stringencies, assembling contigs using fingerprints from individual libraries, checking consensus maps of contigs, and using DNA markers. Altogether, the results demonstrated that the contigs were properly assembled. The apple genome-wide BAC-based physical map represents the first draft genome sequence not only for any member of the large Rosaceae family, but also for all tree species. This map will play a critical role in advanced genomics research for apple and other tree species, including marker development in targeted chromosome regions, fine-mapping and isolation of genes/QTL, conducting comparative genomics analyses of plant chromosomes, and large-scale genomics sequencing. PMID- 17270395 TI - Mutation mechanisms that underlie turnover of a human telomere-adjacent segmental duplication containing an unstable minisatellite. AB - Subterminal regions, juxtaposed to telomeres on human chromosomes, contain a high density of segmental duplications, but relatively little is known about the evolutionary processes that underlie sequence turnover in these regions. We have characterized a segmental duplication adjacent to the Xp/Yp telomere, each copy containing a hypervariable array of the DXYS14 minisatellite. Both DXYS14 repeat arrays mutate at a high rate (0.3 and 0.2% per gamete) but linkage disequilibrium analysis across 27 SNPs and a direct crossover assay show that recombination during meiosis is suppressed. Therefore instability at DXYS14a and b is dominated by intra-allelic processes or possibly conversion limited to the repeat arrays. Furthermore some chromosomes (14%) carry only one copy of the duplicon, including one DXYS14 repeat array that is also highly mutable (1.2% per gamete). To explain these and other observations, we propose there is another low-rate mutation process that causes copy number change in part or all of the duplicon. PMID- 17270397 TI - Distraction osteogenesis versus bilateral sagittal split osteotomy for advancement of the retrognathic mandible: a review of the literature. AB - Bilateral sagittal split osteotomy (BSSO) and distraction osteogenesis (DO) are the most common techniques currently applied to surgically correct mandibular retrognathia. It is the responsibility of the maxillofacial surgeon to determine the optimal treatment option in each individual case. The aim of this study was to review the literature on BSSO and mandibular DO with emphasis on the influence of age and post-surgical growth, damage to the inferior alveolar nerve, and post surgical stability and relapse. Although randomized clinical trials are lacking, some support was found in the literature for DO having advantages over BSSO in the surgical treatment of low and normal mandibular plane angle patients needing greater advancement (>7 mm). In all other mandibular retrognathia patients the treatment outcomes of DO and BSSO seemed to be comparable. DO is accompanied by greater patient discomfort than BSSO during and shortly after treatment, but it is unclear whether this has any consequences in the long term. There is a need for randomized clinical trials comparing the two techniques in all types of mandibular retrognathia, in order to provide evidence-based guidelines for selecting which retrognathia cases are preferably treated by BSSO or DO, both from the surgeon's and the patient's perspective. PMID- 17270396 TI - Neuroanatomical specificity of sex differences in expression of aromatase mRNA in the quail brain. AB - In birds and mammals, aromatase activity in the preoptic-hypothalamic region (HPOA) is usually higher in males than in females. It is, however, not known whether the enzymatic sex difference reflects the differential activation of aromatase transcription or some other control mechanism. Although sex differences in aromatase activity are clearly documented in the HPOA of Japanese quail (Coturnix japonica), only minimal or even no differences at all were observed in the number of aromatase-immunoreactive (ARO-ir) cells in the medial preoptic nucleus (POM) and in the medial part of the bed nucleus striae terminalis (BSTM). We investigated by in situ hybridization the distribution and possible sex differences in aromatase mRNA expression in the brain of sexually active adult quail. The distribution of aromatase mRNA matched very closely the results of previous immunocytochemical studies with the densest signal being observed in the POM, BSTM and in the mediobasal hypothalamus (MBH). Additional weaker signals were detected in the rostral forebrain, arcopallium and mesencephalic regions. No sex difference in the optical density of the hybridization signal could be found in the POM and MBH but the area covered by mRNA was larger in males than in females, indicating a higher overall expression in males. In contrast, in the BSTM, similar areas were covered by the aromatase expression in both sexes but the density of the signal was higher in females than in males. The physiological control of aromatase is thus neuroanatomically specific and with regard to sex differences, these controls are at least partially different if one compares the level of transcription, translation and activity of the enzyme. These results also indirectly suggest that the sex difference in aromatase enzyme activity that is present in the quail HPOA largely results from differentiated controls of enzymatic activity rather than differences in enzyme concentration. PMID- 17270398 TI - Prospective assessment of levetiracetam pharmacokinetics during dose escalation in 4- to 12-year-old children with partial-onset seizures on concomitant carbamazepine or valproate. AB - PURPOSE: To assess the multiple-dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in children with partial-onset seizures and determine whether it is affected by adjunctive carbamazepine or valproate. To correlate levetiracetam concentrations in plasma and saliva and to assess its safety and clinical response. METHODS: Design was an open-label, multicenter study. Twenty one children (4-12 years old) with epilepsy taking carbamazepine (13) or valproate (8) received adjunctive levetiracetam. Levetiracetam was initiated at 20 mg/(kg day) and titrated at 2-week intervals to 40 and then 60 mg/(kg day). Twelve-hour pharmacokinetics were determined at the end of each 2-week period. Efficacy was estimated from the partial seizure frequency per week and Global Evaluation Scale. RESULTS: Levetiracetam was rapidly absorbed following oral dosing, with median t(max) of 0.5 h. Dose proportional increases were observed for C(max) and AUC((0-12)) over the dose range; t(1/2) was 4.9 h. Pharmacokinetics of levetiracetam and ucb L057 were not markedly different with concomitant carbamazepine or valproate; clearance was only 7-13% faster and AUC was decreased by only 15-24% in those on carbamazepine compared to valproate. Levetiracetam did not affect trough carbamazepine or valproate. Concentration in saliva and plasma were strongly correlated. Seizure frequency declined by 50% or more in 43% of subjects in the intent-to-treat population (n=21) and in 56% of those with seizures at baseline (n=16). Marked or moderate improvement occurred in 80% and 75% of patients based on Global Evaluation Scale ratings by investigators and parents/guardians, respectively. Levetiracetam was well tolerated. CONCLUSION: Levetiracetam exhibits simple pharmacokinetics in children, with rapid absorption and dose-proportional kinetics. Small but not clinically relevant differences were observed between subjects receiving carbamazepine and valproate, suggesting significant dose adjustment is usually not necessary. This substantiates prior assessments that levetiracetam clearance is higher in children than adults, necessitating a higher dose in children on a mg/kg basis, and suggests it is useful add-on therapy for children with partial onset seizures regardless of baseline therapy. PMID- 17270399 TI - Predictors of insight in psychotic inpatients. PMID- 17270400 TI - Epigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder. AB - In the cerebral prefrontal cortex (PFC), DNA-methyltransferase 1 (DNMT1), the enzyme that catalyzes the methylation of cytosine at carbon atoms in position 5 in CpG dinucleotides, is expressed selectively in GABAergic neurons and is upregulated in layers I and II of schizophrenia (SZ) and bipolar disorder patients with psychosis (BDP). To replicate these earlier findings and to verify whether overexpression of DNMT1 and the consequent epigenetic decrease of reelin and glutamic acid decarboxylase (GAD) 67 mRNA expression also occur in GABAergic medium spiny neurons of the caudate nucleus (CN) and putamen (PT) of SZ and BDP, we studied the entire McLean 66 Cohort (Harvard Brain Tissue Resource Center, McLean Hospital, Belmont, MA) including SZ and BDP, which were matched with nonpsychiatric subjects. The data demonstrate that in GABAergic medium spiny neurons of CN and PT, unlike in GABAergic neurons of layer I and II PFC, the increased expression of DNMT1 and the decrease of reelin and GAD67 occur in SZ but not in BDP. This suggests that different epigenetic mechanisms must exist in the pathogenesis underlying SZ and BDP and implies that these disorders might involve two separate entities that are characterized by a well-defined neuropathology. PMID- 17270401 TI - Recombinant human platelet-derived growth factor enhanced dermal wound healing by a pathway involving ERK and c-fos in diabetic rats. AB - BACKGROUND: Platelet-derived growth factor (PDGF) has been shown to promote dermal wound healing, however, the molecular mechanisms responsible for are not fully understood. OBJECTIVE: The present study was undertaken to investigate the possible signaling mechanisms by which PDGF improved healing of cutaneous wound in diabetic rats. METHODS: Four full-thickness skin wounds were created on the dorsum of Wistar diabetic rats. Animals were treated with or without recombinant human PDGF (rhPDGF) at 7.0 microg/cm(2) wound or vehicle daily 1 day after wounding. The animals were then killed after various intervals of wounding, and the wounded skin tissues were used for histological evaluation, analysis of the phosphorylation of extracellular signal-regulated kinases (ERK) and the expression of c-fos protein, as well as the labeling indices of proliferative cell nuclear antigen (PCNA). RESULTS: Topical application of rhPDGF significantly accelerated the rate of reepithelialization compared with vehicle-treated or untreated group at 7 days after wounding. At the histological level, the significant increases in the degree of reepithelialization, the thickness of granulation tissue and the density of capillary bud were observed in the wound sites in rhPDGF-treated group at 7 and 14 days after wounding. Moreover, treatment with rhPDGF increased PCNA labeling indices, c-fos protein expression and ERK phosphorylation in the wounded tissues at the indicated time after wounding. CONCLUSION: These results suggest that application of rhPDGF increases cell proliferation, and enhances dermal tissue repair in diabetic skin lesion of rats, which might be partly mediated by ERK activation and c-fos protein expression. PMID- 17270402 TI - Possible role of integrase gene polymerase chain reaction as an epidemiological marker: study of multidrug-resistant Acinetobacter baumannii isolated from nosocomial infections. AB - Eighty-six strains of Acinetobacter baumannii from India and Nepal were investigated for the presence of integrons in relation to multiple drug resistance by integrase gene polymerase chain reaction (PCR). Integrons were found to be present at a rate of 43.02% (37/86). Integrons were significantly correlated with multidrug resistance to several antibiotics. Class 1 integrons were detected in 81.1% of integron-positive strains, whilst 18.9% were found to be positive for class 2 integrons. The majority of class 2 integrons (71%) were encountered in strains isolated from post-operative wards of both countries. The highest integron carriage in isolates of A. baumannii (63.6%) was observed in 2005. Hence, it is likely that integrons play an important role in antibiotic resistance and possibly indicate epidemic behaviour of A. baumannii. Integrase gene PCR may be used as routine screening and identification for the surveillance of clinical isolates of A. baumannii with epidemic potential. PMID- 17270403 TI - Metabolic syndrome pathophysiology: the role of adipose tissue. AB - Several pathophysiological explanations for the metabolic syndrome have been proposed involving insulin resistance, chronic inflammation and ectopic fat accumulation following adipose tissue saturation. However, current concepts create several paradoxes, including limited cardiovascular risk reduction with intensive glucose control in diabetics, therapies that result in weight gain (PPAR agonists), and presence of some of the metabolic traits among some lipodystrophies. We propose the functional failure of an organ, in this case, the adipose tissue as a model to interpret its manifestations and to reconcile some of the apparent paradox. A cornerstone of this model is the failure of the adipose tissue to buffer postprandial lipids. In addition, homeostatic feedback loops guide physiological and pathological adipose tissue activities. Fat turnover is determined by a complex equilibrium in which insulin is a main factor but not the only one. Chronically inadequate energy balance may be a key factor, stressing the system. In this situation, an adipose tissue functional failure occurs resulting in changes in systemic energy delivery, impaired glucose consumption and activation of self-regulatory mechanisms that extend their influence to whole body homeostasis system. These include changes in adipokines secretion and vascular effects. The functional capacity of the adipose tissue varies among subjects explaining the incomplete overlapping among the metabolic syndrome and obesity. Variations at multiple gene loci will be partially responsible for these interindividual differences. Two of those candidate genes, the adiponectin (APM1) and the perilipin (PLIN) genes, are discussed in more detail. PMID- 17270404 TI - Probing the skin permeation of eicosapentaenoic acid and ketoprofen 2. Comparative depth profiling and metabolism of eicosapentaenoic acid. AB - Unexpected enhancement of the topical delivery of eicosapentaenoic acid (EPA) across porcine skin was observed previously when fish oil was co-formulated with ketoprofen. In the current work depth profile analysis was used to probe the epidermal conversion of EPA to its 15-hydroxy metabolite in the presence and absence of ketoprofen. Freshly excised full-thickness porcine skin in Franz diffusion cells was dosed (both infinite and finite) with simple formulations based on fish oil as source of EPA. After 24h the skin was subjected to tape stripping and depth profiles were constructed. Typical depth profiles were obtained, with an inverse relationship between depth and permeant concentration. 15-HEPE was generated in the skin when Hepes-modified Hanks' balanced salt solution was used, but none was detected when a cetrimide receptor phase was used, highlighting the importance of maintaining skin viability in such exercises. Ketoprofen had a direct influence on the metabolism of EPA and resulting in conversion to its 15-LOX metabolite 15-HEPE. However, this link appears to be only part of the solution of EPA enhancement however, as even in non-viable skin ketoprofen had an enhancing affect. PMID- 17270405 TI - Phase transformations of erythromycin A dihydrate during pelletisation and drying. AB - An at-line process analytical approach was applied to better understand process induced transformations of erythromycin dihydrate during pellet manufacture (extrusion-spheronisation and drying process). The pellets contained 50% (w/w) erythromycin dihydrate and 50% (w/w) microcrystalline cellulose, with purified water used as a granulating fluid. To characterise changes in solid-state properties during processing, near infrared (NIR) spectroscopy and X-ray powder diffraction (XRPD) were applied. Samples were taken after every processing step (blending, granulation, extrusion, and spheronisation) and at predetermined intervals during drying at 30 or 60 degrees C. During pelletisation and drying at 30 degrees C no changes occurred. Partial transformation to the dehydrated form was observed for the pellets dried at 60 degrees C by NIR and XRPD. The variable temperature XRPD measurements of the wet pellets (from 25 to 200 degrees C) also confirmed the change to erythromycin dehydrate at approximately 60 degrees C. PMID- 17270406 TI - Reversible effects of permeation enhancers on human skin. AB - This study outlines a systematic approach for investigating a desired characteristic of chemicals used to facilitate the permeation of drugs across the skin that is, the reversibility of the permeation enhancement effect. This implies that the vital skin barrier function is restored and not permanently impaired after the application of these enhancers. The reversible effects of two terpene enhancers, (R)-(-)-carvone and eucarvone, on excised human skin were evaluated by in vitro permeation and extraction studies on normal (untreated) and enhancer-pretreated epidermis, respectively. For the permeation studies on normal epidermis, the donor solutions were the model drug, haloperidol (HP, 3mg/ml), in propylene glycol (PG) with or without 5% (w/v) enhancer and for the extraction studies using epidermis pretreated with enhancer, a solution of HP (3mg/ml) in PG was used. The solubilities of the enhancers in 0.03% lactic acid (receptor solution) and of HP in PG (donor solution) were determined to demonstrate that the sink and saturated conditions were maintained in the respective compartments of the flow-through cells throughout the in vitro experiments. (R)-(-)-Carvone cleared out of the skin faster than eucarvone. This could be due to the 4-fold higher skin permeability of (R)-(-)-carvone compared to that of eucarvone. The amount of HP deposited in the epidermis was much lower in the eucarvone pretreated epidermis than that pretreated with (R)-(-)-carvone. The permeation profile of HP across the enhancer-pretreated skin was 4-fold greater than in the vehicle alone (control), but similar to that across untreated skin with enhancer present in the donor solution, indicating that permeation across the enhancer pretreated skin did not change. The enhancing effects of both terpenes on the skin were found to be reversible and the permeability of the skin was left intact after the passage of the drug in the vehicle with these enhancers. PMID- 17270408 TI - Optimisation of polyherbal gels for vaginal drug delivery by Box-Behnken statistical design. AB - The present research work aimed at development and optimisation of mucoadhesive polyherbal gels (MPG) for vaginal drug delivery. As the rheological and mucoadhesive properties of the gels correlate well to each other the prepared MPGs were optimised for maximum mucoadhesion using a relationship between the storage modulus (G') and Gel Index (GI), by employing a 3-factor, 3-level Box Behnken statistical design. Independent variables studied were the polymer concentration (X(1)), honey concentration (X(2)) and aerosil concentration (X(3)). Aerosil has been investigated for the first time to improve the consistency of gels. The dependent variables studied were the elastic modulus, G'(Y(1)), gel index (Y(2)), and maximum detachment force (Y(3)) with applied constraints of 5000.05) in inorganic soluble solids between the water extract of irradiated and unirradiated aniseeds. Sensory evaluation indicated that gamma irradiation improved sensory characteristics of aniseed water extract tested immediately after irradiation; however, after 12 months of storage, no significant differences (p>0.05) were found in color, taste or flavor between extract of irradiated and unirradiated seeds. PMID- 17270434 TI - Structure-activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5. AB - Necrostatin-5 (Nec-5) is a novel potent small-molecule inhibitor of necroptosis structurally distinct from previously described Necrostatin-1 (Nec-1), and therefore, represents a new direction for the inhibition of this cellular caspase independent necrotic cell death mechanism. Here, we describe a series of structural modifications of Nec-5 and the structure-activity relationship (SAR) of Nec-5 series in inhibiting necroptosis. PMID- 17270435 TI - Bis-styrylpyridine and bis-styrylbenzene derivatives as inhibitors for Abeta fibril formation. AB - New bis-styrylpyridine and bis-styrylbenzene derivatives were designed and synthesized. These 34 compounds were evaluated by Abeta fibril formation inhibitory assay using thioflavin T as a dye (named ThT assay). Most of them showed excellent inhibitory activities for Abeta fibril formation at IC50 of 0.1 2.7 microM which is comparable to curcumin (IC50 of 0.8 microM). Among them, nine compounds were screened for their cytotoxicities on HT-22 cell by MTT assay at 1, 10, and 50 microM. In particular, I-7 and II-2 exhibited the best combination of inhibitory activity and compound cytotoxicity. PMID- 17270436 TI - Chemoenzymatic synthesis and in vitro studies on the hydrolysis of antimicrobial monoglycosyl diglycerides by pancreatic lipase. AB - Monoglucosyl and monogalactosyl diglycerides (MGDGs) with medium-long length acyl chains, identified as active components in Euphorbiaceae, were synthesized. They were examined for antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. MGDGs with two octanoyl groups at both 1- and 2-positions showed the most potent activity. The stereoselectivity of pancreatic lipase was investigated in vitro where the preference for the 1 position in MGDGs is strictly related to the length of the acyl chains. PMID- 17270437 TI - New C-5 substituted pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. AB - Novel C-5 substituted pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket. PMID- 17270438 TI - Immunomodulatory effects of two sapogenins 1 and 2 isolated from Luffa cylindrica in Balb/C mice. AB - Two Triterpenoids (sapogenins 1 and 2) isolated from Luffa cylindrica were subjected to immunomodulatory activity in male Balb/c mice. Mice were treated with three doses of sapogenins 1 and 2 (10, 30 and 100 mg/kg) and levamisole (2.5 mg/kg) used as a standard reference drug for 15 days. Immune responses to T dependent antigen SRBCs were observed using parameters like HA, PFC, DTH, lymphocyte proliferation and phagocytosis. As regards these parameters, sapogenins 1 and 2 elicited a significant increase in the HA, PFC and DTH response at dose 10 mg/kg (P<0.01) and 100 mg/kg (P<0.001), respectively. Sapogenins 1 and 2 also showed significant dose-dependent decrease and increase in lymphocyte proliferation assay and phagocytic activity of macrophages. Overall, sapogenins 1 and 2 showed dose relative immunostimulatory effect on in vivo immune functions in mice. PMID- 17270439 TI - Novel hydroxamic acid-related phosphinates: inhibition of neutral aminopeptidase N (APN). AB - Here we describe the inhibitory activity toward neutral aminopeptidase of three new families of phosphinate inhibitors related in structure to hydroxamic acids. These compounds, even as racemic mixtures, are good inhibitors of APN and show strong structure activity relationship (SAR) depending on the substituents in P1 and P1' positions. PMID- 17270440 TI - Evaluation of nitroalkenes as nitric oxide donors. AB - Chemiluminescence experiments demonstrate that simple nitroalkenes release low levels of nitric oxide. UV and EPR measurements suggest but cannot confirm direct NO release from nitroalkenes. Given the biological activity of nitrated unsaturated fatty acids, these results suggest the possible metabolic conversion of nitroalkenes to NO. PMID- 17270441 TI - Lead optimization of 5,6-diarylpyridines as CB1 receptor inverse agonists. AB - Optimization of the biological activity for 5,6-diarylpyridines as CB1 receptor inverse agonists is described. Food intake and pharmacokinetic evaluation of 3f and 15c indicate that these compounds are effective orally active modulators of CB1. PMID- 17270442 TI - Glucosamine sulfate promotes osteoblastic differentiation of MG-63 cells via anti inflammatory effect. AB - Glucosamine sulfate (SGlc) has been known to be effective in controlling osteoarthritis (OA) symptoms in several clinical studies. However, the mechanisms of this positive effect of SGlc in human OA still remain elusive. Therefore, first, the effects of SGlc on the differentiation of osteoblast-like MG-63 cells were investigated. Our results demonstrate that SGlc can increase ALP activity, collagen synthesis, osteocalcin secretion, and mineralization in osteoblastic cells in vitro. Furthermore, it was observed that SGlc exhibited anti inflammatory effect on production of TNF-alpha, IL-1beta, and PGE(2) in macrophage, RAW264.7 cells. In conclusion, these results suggest that SGlc can promote cell differentiation in cultured MG-63 osteoblast cells via anti inflammatory effect. PMID- 17270443 TI - Studies on acyl pyrrolidine inhibitors of HCV RNA-dependent RNA polymerase to identify a molecule with replicon antiviral activity. AB - The SAR development is described for a series of N-acyl pyrrolidine inhibitors of the Hepatitis C virus RNA-dependent RNA polymerase, NS5B, from tractable Delta21 enzyme inhibitors to an example with antiviral activity in a cellular assay (HCV replicon). PMID- 17270444 TI - Bile acid-based receptors containing 2,6-bis(acylamino)pyridine for recognition of uracil derivatives. AB - Hydrogen-bonding interactions of steroid-based cyclic and acyclic receptors containing 2,6-bis(acylamino)pyridine with uracil derivatives were studied in CDCl(3). Acyclic receptors show better binding behaviour as compared to cholaphanes with uracil derivatives. PMID- 17270445 TI - Quality of breast imaging reports falls short of recommended standards. AB - Initial diagnosis and treatment of women with breast cancer is based on the imaging findings. Anecdotal experience suggests that the quality of breast imaging reports is variable; however, systematic evaluation of the content of reports has not been documented to date. We present an audit of the breast imaging reports of all new breast cancer cases referred to a multidisciplinary breast centre during 2004, based on 244 imaging reports from 253 cases. We focus on the quality of imaging reports from the perspective of completeness, concordance with standards, and provision of information considered relevant to clinical decision-making. The audit shows that many reports do not provide key information, and that there are substantial variations in the quality of reports between breast screening services (as part of a coordinated national programme) and community-based radiology services. About one-quarter of all reports do not provide an imaging diagnosis, and only half of all imaging reports are concordant with standards for structured reporting. The least reported variables were breast density category (reported in 24%), lesion depth (37%), lesion shape (55% for mammography, 39% for ultrasound), and location (59%). The most frequently provided information was mammography lesion type (99.6%), sonographic lesion size (90.4%), and recommendation for further investigation (89%). The vast majority of reports from screening services used structured reporting, and these were more likely to provide the information recommended in standards than were reports from community-based radiologists. This work indicates that the quality (content and completeness) of breast imaging reports, particularly community-based radiology reports, is not in line with standards. The clinical implications of these findings warrant further study. PMID- 17270446 TI - Kinematic characterization of functional reach to grasp in normal and in motor disabled children. AB - The upper limb kinematics were assessed during the execution of a functional task in healthy adults, children and in children with motor disabilities (i.e. hemiplegic cerebral palsy (HCP) and movement disorders (MD)). The quantitative assessment was performed considering the time durations, the amplitude of movements at different joints and the periodicity of the acceleration patterns. Compared to adults, healthy children showed increased motion amplitudes both at the head and at the trunk; this is suggestive of a reduced ability to stabilize the head during reaching. Furthermore, healthy children showed a reduced periodicity of the acceleration patterns which is interpreted as an indication of the on-going maturation process of the central nervous system. Subjects with HCP and MD showed increased movement duration; however this general finding does not account for specific differences. Indeed, children with HCP showed reduced range of motion (ROM) of the shoulder on the frontal plane which is counterbalanced by the introduction of compensatory movements of the trunk. Conversely, in children with MD, the ROM is well-preserved whereas the movements of the head are increased especially at higher speed. Finally, the periodicity of the end-effect is dramatically reduced both in HCP and MD. This suggests the existence of out-of phase corrective strokes that may indicate an increased variability of the motor control commands. The results of this study reinforce the evidence that kinematic analysis may add valuable information to understand the developmental process in healthy children and to differentiate distinct levels of impairment in children with neurological disorders. PMID- 17270447 TI - Perimetric homonymous visual field loss post-stroke. AB - Post-stroke homonymous visual field (PSHVF) loss has functional and driving implications for patients. Automated, as opposed to confrontational, assessment of PSHVF loss has the potential to provide a more reliable indicator for field loss and thus ability to drive. Sixty-one consecutive stroke admissions were assessed at 9 months post-stroke. Driving status and the patient's awareness of any visual field loss was ascertained. Patients underwent formal perimetric visual field testing using a Humphrey Visual Field Analyser II. A separate, blinded, confrontational assessment of visual fields was made using the National Institutes of Health Stroke Scale (NIHSS) technique. Homonymous field defects were found in 10 (16%) patients, with 50% of these being hemianopia and 50% quadrantanopia. Right-sided field loss was more common (70%). No patients with PSHVF loss were aware of their loss, and only two were detected using NIHSS assessment. One patient was thought to have PSHVF loss on NIHSS assessment but this was not confirmed on perimetry. Of those with significant PSHVF loss at 9 months, 30% were driving. The prevalence of PSHVF loss is relatively high and is underestimated by confrontational testing. Stroke patients are often unaware of their field loss, with up to 5% driving with significantly affected visual fields at 9 months. Perimetric testing may be useful in decision-making regarding driving eligibility post-stroke. PMID- 17270449 TI - Systematic interconnected web-like architecture growth of sprayed TiO2 films. AB - Systematic improvement in interconnected web-like architecture with thickness of TiO2 films synthesized by spray pyrolysis method is reported and characterized for the structural, optical, surface morphological, and wettability properties. Deposited TiO2 films were crystalline with [120] direction orientation, uniform and adherent to the glass substrate. Interestingly, with increase in film thickness, fuzzy and blurred web-like architecture becomes more clear and sharp with well-defined boundaries. The band gap energy was decreased with increase in film thickness. Change in surface architecture resulted into smaller surface wettability in thick film compared to thin one. PMID- 17270448 TI - Hydatid cysts of the internal acoustic canal and jugular foramen. AB - Brain involvement with hydatid disease occurs in 1-2% of all Echinococcus granulosus infections. Cerebral hydatid cysts are usually supratentorial, whereas infratentorial lesions are quite rare. Here we report a 19-year-old man with hydatid cysts in the right cerebellopontine cistern with the involvement of internal acoustic canal and jugular foramen. The patient presented with signs of increased intracranial pressure and multiple cranial nerve palsies. Surgery was performed in the semi-sitting position using a lateral suboccipital approach for a right-sided craniotomy. Magnetic resonance imaging clearly demonstrated cisternal, neural and vascular relationships which aided in intact surgical removal of the lesion using microsurgical techniques. Total removal without rupture should be the surgical goal in all hydatid cysts. PMID- 17270450 TI - Preparations of PAN-based adsorbers for separation of cesium and cobalt from radioactive wastes. AB - Ion-exchange adsorbers are widely used for radioisotope separation, as well as for the removal of hazardous fission products from aqueous waste prior to discharge to the environment. Inorganic exchangers are of particular interest because of their resistance to radiolytic damage and selectivity for specific fission products. Composite inorganic-organic adsorbers represent a group of inorganic ion exchangers modified by using binding organic material, polyacrylonitrile, for preparation of larger size particles with higher granular strength. At the same time, kinetics of ion exchange and sorption capacity of such composite adsorbers are not influenced by the binding polymer. The contents of active component in composite adsorber were varied over a very broad range of 5-95% of the dry weight of the composite adsorber, and tested for separation and concentration of various stimulated wastes. Three different inorganic sorbents, granular hexacyanoferrate-based ion exchanger, were developed for the removal of Cs and Co ions from waste solutions containing different complexing agents as detergents. Radiation and thermal stability studies show that these adsorbents can be used for medium-active waste treatment. PMID- 17270451 TI - Determination of weathering rate of the Morro do Ferro Th-REEs deposit, Brazil using U-isotope method. AB - The weathering rate was estimated by changes in (234)U/(238)U activity ratio (AR) and U content of rocks, borehole spoil and surface water samples at the Morro do Ferro Th-REEs deposit. The deposit is situated in the Pocos de Caldas alkaline massif, Brazil. The south stream basin investigated in this paper has not been significantly affected by anthropogenic inputs of pollutants as compared to the Corumbatai River basin in Sao Paulo State, where the method was previously applied. The weathering rate derived utilizing the U-isotopes modeling corresponded to 0.015 mm/yr (67,000 years to weather 1m of rock under the actual climatic conditions). The estimated rate is very reasonable in comparison with the range of 0.015-0.05 mm/yr of land surface lowering within the entire caldera. It is also compatible with a rate of 0.013 mm/yr determined for the Salgado River basin in a semi-arid region in Bahia State, Brazil. The value generated is reliable and increases the potential use of the method for other different areas in Brazil and elsewhere, because it may be used in regions with different climatic conditions and (un)polluted basins. PMID- 17270452 TI - Contribution of CYLN2 and GTF2IRD1 to neurological and cognitive symptoms in Williams Syndrome. AB - Williams Syndrome (WS, [MIM 194050]) is a disorder caused by a hemizygous deletion of 25-30 genes on chromosome 7q11.23. Several of these genes including those encoding cytoplasmic linker protein-115 (CYLN2) and general transcription factors (GTF2I and GTF2IRD1) are expressed in the brain and may contribute to the distinct neurological and cognitive deficits in WS patients. Recent studies of patients with partial deletions indicate that hemizygosity of GTF2I probably contributes to mental retardation in WS. Here we investigate whether CYLN2 and GTF2IRD1 contribute to the motoric and cognitive deficits in WS. Behavioral assessment of a new patient in which STX1A and LIMK1, but not CYLN2 and GTF2IRD1, are deleted showed that his cognitive and motor coordination functions were significantly better than in typical WS patients. Comparative analyses of gene specific CYLN2 and GTF2IRD1 knockout mice showed that a reduced size of the corpus callosum as well as deficits in motor coordination and hippocampal memory formation may be attributed to a deletion of CYLN2, while increased ventricle volume can be attributed to both CYLN2 and GTF2IRD1. We conclude that the motor and cognitive deficits in Williams Syndrome are caused by a variety of genes and that heterozygous deletion of CYLN2 is one of the major causes responsible for such dysfunctions. PMID- 17270453 TI - Nerve growth factor promotes survival of new neurons in the adult hippocampus. AB - Exogenously provided NGF enhances cognitive performance in impaired rodents and humans and is currently a promising compound for the treatment of dementia. To investigate whether NGF-dependent cognitive improvement may be due in part to increased hippocampal neurogenesis, adult and aged male rats were treated with NGF or vehicle intracerebroventricularly for 6 or 20 days followed by evaluation of cholinergic parameters and hippocampal neurogenesis. We show that NGF increases hippocampal cholinergic activity as rapidly as 3 days after initiation of treatment. NGF treatment for 6 days did not affect proliferation of progenitor cells in the dentate gyrus granule cell layer (GCL). However, continuous NGF infusion enhanced survival of new neurons in the GCL of young adult, but not aged rats. Taken together, these findings suggest that NGF, likely mediated through increased cholinergic tone, promotes neurogenesis in the adult hippocampus, which may relate to the nootropic action of NGF. PMID- 17270454 TI - Soluble adhesion molecules and angiotensin-converting enzyme in dementia. AB - We aimed to determine plasma and cerebrospinal fluid (CSF) levels of angiotensin converting enzyme (ACE) and the soluble forms of intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and platelet endothelial cell adhesion molecule-1 (sPECAM-1) as surrogate markers for endothelial cell activation in clinically diagnosed patients with Alzheimer's disease (AD, n=260), dementia with Lewy bodies (DLB, n=39) and non-demented controls (n=34). Plasma sICAM-1 and sPECAM-1 were higher and CSF sVCAM-1 were lower in AD and DLB patients than in controls (p<0.001). DLB patients had higher CSF sICAM-1, but lower CSF sVCAM-1 (p<0.001). No difference in ACE levels was found between the dementia groups and controls. In controls and AD patients CSF sICAM and sVCAM-1 strongly correlated with each other and with blood barrier permeability whereas in DLB group these correlations were weaker. The observed patterns in adhesion molecules may reflect distinctions in the pathophysiological basis of their generation in dementia patients. PMID- 17270455 TI - Rapamycin is a neuroprotective treatment for traumatic brain injury. AB - The mammalian target of rapamycin, commonly known as mTOR, is a serine/threonine kinase that regulates translation and cell division. mTOR integrates input from multiple upstream signals, including growth factors and nutrients to regulate protein synthesis. Inhibition of mTOR leads to cell cycle arrest, inhibition of cell proliferation, immunosuppression and induction of autophagy. Autophagy, a bulk degradation of sub-cellular constituents, is a process that keeps the balance between protein synthesis and protein degradation and is induced upon amino acids deprivation. Rapamycin, mTOR signaling inhibitor, mimics amino acid and, to some extent, growth factor deprivation. In the present study we examined the effect of rapamycin, on the outcome of mice after brain injury. Our results demonstrate that rapamycin injection 4 h following closed head injury significantly improved functional recovery as manifested by changes in the Neurological Severity Score, a neurobehavioral testing. To verify the activity of the injected rapamycin, we demonstrated that it inhibits p70S6K phosphorylation, reduces microglia/macrophages activation and increases the number of surviving neurons at the site of injury. We therefore suggest that rapamycin is neuroprotective following traumatic brain injury and as a drug used in the clinic for other indications, we propose that further studies on rapamycin should be conducted in order to consider it as a novel therapy for traumatic brain injury. PMID- 17270456 TI - Physiological and biochemical responses to acute ozone-induced oxidative stress in Medicago truncatula. AB - Oxidative signaling mediated by reactive oxygen species (ROS) is a central component of biotic and abiotic stresses in plants. Acute ozone (O(3)) fumigation is a useful non-invasive treatment for eliciting endogenous ROS in planta. In this study, 38 different accessions of the model legume, Medicago truncatula, from various geographical regions were fumigated with 300 nmol mol(-1) of O(3) for a period of six hours. Phenotypic symptoms were evaluated 24 and 48 h after the end of treatment. A majority of the accessions showed distinct visible damage. Eight accessions showing varying sensitivities to ozone were subjected to biochemical analysis to evaluate correlations between ozone damage and levels of ROS, antioxidants, and lipid peroxidation. Two-way analysis of variance indicated highly significant interactions between O(3) damage and levels of ROS, ascorbate, glutathione and lipid peroxidation. There were significant differences among the accessions for these traits before and after the end of O(3) fumigation, as indicated by equal variance Student's t-test. This study suggests that multiple physiological and biochemical mechanisms may govern O(3) tolerance or sensitivity. Surveying a large collection of germplasm led to identification of multiple resistant and sensitive lines for investigating molecular basis of O(3) phytotoxicity. The most resistant JE154 accession also showed enhanced tolerance to chronic O(3) and dehydration stress, suggesting germplasm with increased tolerance to acute O(3) can be a useful resource for improving resistance to multiple abiotic stressors. PMID- 17270457 TI - Reconstructive surgery in active mitral valve endocarditis: feasibility, safety and durability. AB - OBJECTIVE: To evaluate timing for surgery and management of complex valve lesions in patients with active mitral valve (MV) endocarditis. Results are based on 13 years of experience with MV repair in active endocarditis. METHOD: Between 1993 and 2005, 81 patients were operated for active MV endocarditis, of which 63 (or 78%) had MV repair. For all patients, the median time between diagnosis and surgery was 10 days. Diverse surgical techniques were applied to restore MV competence. In 59% of the patients, pericardial patches, tricuspid autograft or partial MV homografts were used as leaflet substitutes. In addition, prosthetic rings were employed in 44% of the patients. RESULTS: The overall operative mortality was 17.5%. However, considering only patients in preoperative NYHA class I or II, the operative mortality could be reduced to 4.8%. NYHA class > or =3, elevated age (above 70 years) and history of valvular were the three independent risks factors for early mortality in our multivariate analysis. The average follow-up time was 60+/-37 months. During this period, five late deaths occurred, two of which were cardiac-related. The overall 5- and 10-year survival rate was 73+/-12% and 69+/-13%, respectively. In hospital survivors, freedom from cardiac death after 5 and 10 years was 93+/-8%. Three early and five late MV reoperations occurred in seven patients, of them four could have MV re-repair. Only one endocarditis recurrence occurred after 4 months in a chronic haeamodialysed patient. Freedom from MV reoperation was 89+/-10% and 72+/-24% at 5 and 10 years, respectively. Ten-year freedom from MV replacement and from endocarditis recurrence were 95+/-5% and 98+/-1%, respectively. Annular abscesses and calcified or rheumatic MV disease were two independent risk factors associated with reoperation in our multivariate analysis. During the follow-up period, all patients were in NYHA class I or II; 89% of patients had mitral regurgitation grade < or =I, only 11% had grade II on transthoracic echocardiography. CONCLUSION: Using diverse and advanced techniques of MV repair, a reparability rate of 80% can be reached among patients with active endocarditis. We demonstrate that a high level of safety and excellent durability of MV repair can be obtained even for complex repairs. PMID- 17270458 TI - Neonatal repair of right interrupted aortic arch, aberrant left subclavian artery, ventricular septal defect and retroaortic innominate vein. AB - We report a rare case of neonatal biventricular repair of a right interrupted aortic arch (type B), with an aberrant left subclavian artery, ventricular septal defect and retroaortic innominate vein in a 4-week-old, 2.7 kg neonate with DiGeorge syndrome. The patient had an unremarkable postoperative recovery. We discuss the anatomy of this rare congenital anomaly, its surgical implications and issues surrounding the adequacy of the left ventricular outflow tract. PMID- 17270459 TI - Parallel changes in non-photochemical quenching properties, photosynthesis and D1 levels at sudden, prolonged irradiance exposures in Ulva fasciata Delile. AB - The photosynthetic response to a sudden and prolonged high irradiance exposure and following recovery at low irradiance were studied with the aim of investigating the ability to withstand and adapt to high irradiance without prior high light adaptation. When thalli of Ulva fasciata, accustomed to a low irradiance (80 micromol photons m(-2) s(-1)), were exposed to a high irradiance (1500 micromol photons m(-2) s(-1)), the D1 protein was rapidly degraded, reaching a steady-state level after 110 min. This was followed by a fast recovery when thalli were transferred to dim light. The overall ability of non photochemical quenching of chlorophyll fluorescence decreased and levelled off at a sudden and prolonged exposure to high irradiance and followed the same trend as the D1 level with a fast recovery in dim light. Ulva had intrinsic means to acclimate rapidly to high irradiance, when non-photochemical quenching did not operate properly, by maintaining a smaller fraction of high light tolerant PSII assemblages and by maintaining a high non-photochemical quenching capacity of chlorophyll fluorescence in relation to the variable fluorescence. The overall absorption of light (400-700 nm) remained high during the period of high irradiance exposure. When Ulva were deprived of nutrients in the form of PES media the ability of non-photochemical quenching decreased at photoinhibitory conditions. The possible causes for the responses at prolonged irradiance and the mechanisms for the decrease of non-photochemical quenching are discussed, with implications for field measurements. PMID- 17270460 TI - Macrophage inflammatory protein-1alpha: a link between innate immunity and familial Mediterranean fever? AB - The aim of this study is to investigate the relationship between chemokines and the inflammation in Familial Mediterranean Fever (FMF). Forty-nine patients with FMF (41 in remission and 8 in acute attack period) and 20 healthy controls were included in the study. Serum levels of macrophage inflammatory protein-1alpha (MIP-1alpha) were assessed in the patients and the controls, along with other parameters of disease activity, i.e., fibrinogen, C-reactive protein and erythrocyte sedimentation rate. Serum MIP-1alpha levels of the patients with FMF in acute attack period were significantly higher than the patients in remission and healthy controls (p=0.02 and p=0.038, respectively). MIP-1alpha levels were weakly correlated with CRP (r=0.32, p=0.032) levels. MIP-1alpha may have a role in the pathogenesis of FMF attacks. MIP-1alpha and other chemokines may constitute a link between the innate immune system and FMF. PMID- 17270461 TI - Effect of IL-1 on the hydrolysis of the tumor antigen epitope gp100(280-288) by fibroblast-expressed enzymes. AB - The role of proinflammatory cytokines in increasing the activity of specific proteases suggests the hypothesis that, by altering the expression of these mediators, adjuvants may modulate the effectiveness of peptides used as vaccines. The possible effect of IL-1 on fibroblast-expressed, peptidases was, thus, investigated by analyzing the degradation of a tumor antigen epitope (gp100(280 288), YLEPGPVTA) in the presence of cultured human fibroblasts. The data obtained indicate an increase of substrate hydrolysis after IL-1 treatment as compared with non-treated controls. Hydrolysis increase was accompanied by defined changes in the population of the by-products formed: specifically, the amount of peptidic by-products increased more than the amount of single amino acids, and the amount of the C-terminal by-products increased more than the amount of their N-terminal counterpart. These data appear to indicate that the positive effect of IL-1 on the activity of substrate-active enzymes is function of modified expression of a number of these enzymes by fibroblasts. From these data it can be inferred that the use of IL-1-inducing adjuvants, increasing the activity of peptidases expressed by bystander cells, may reduce the bio-availability of peptides used for immunization. PMID- 17270462 TI - Overexpression and purification of single zinc finger peptides of human zinc finger protein ZNF191. AB - ZNF191, a new human zinc finger protein, probably relates to some hereditary diseases and cancers. To obtain structural information of zinc finger domain a convenient method for obtaining milligram quantities of each zinc finger peptide of ZNF191 is necessary. Here, we report an Escherichia coli expression system for rapid and high-level expression of zinc finger 3 and zinc finger 4 of ZNF191. The gene of zinc finger 3 or zinc finger 4 was cloned into pET31b vector to allow expression of single zinc finger peptide as a ketosteroid isomerase (KSI) fusion protein. The KSI-single zinc finger fusion protein was overexpressed in the form of inclusion body, which can be purified by washing several times using buffer solutions, and then be cleaved directly by cyanogen bromide to release single zinc finger peptide. The more than 20mg/L yield of single zinc finger peptide was achieved with more than 95% purity by using YM ultrafiltration membranes. Circular dichroism spectra of these two single zinc finger peptides titrated with Zn(2+) ions demonstrate that they have different secondary structures. PMID- 17270463 TI - Membrane associated qualitative differences in cell ultrastructure of chemically and high pressure cryofixed plant cells. AB - Membrane contrast can sometimes be poor in biological samples after high pressure freezing (HPF) and freeze substitution (FS). The addition of water to the FS medium has been shown to improve membrane contrast in animal tissue and yeast. In the present study we tested the effects of 1% and 5% water added to the FS-medium (2% osmium with 0.2% uranyl acetate in anhydrous acetone) on the quality and visibility of membranes in high pressure frozen leaf samples of Cucurbita pepo L. plants and compared them to chemically fixed cells (3% glutaraldehyde post-fixed with 1% osmium tetroxide). The addition of water to the FS-medium drastically decreased the amounts of well preserved cells and did not significantly improve the quality nor visibility of membranes. In samples that were freeze substituted in FS-media containing 1% and 5% water the width of thylakoid membranes was found to be significantly increased of about 20% and the perinuclear space was up to 76% wider in comparison to what was found in samples which were freeze substituted without water. No differences were found in the thickness of membranes between chemically and cryofixed cells that were freeze substituted in the FS-medium without water. Nevertheless, in chemically fixed cells the intrathylakoidal space was about 120% wider than in cryofixed cells that were freeze substituted with or without water. The present results demonstrate that the addition of water to the FS-medium does not improve membrane contrast but changes the width of thylakoid membranes and the perinuclear space in the present plant material. The addition of water to the FS-medium is therefore not as essential for improved membrane contrast in the investigated plant samples as it was observed in cells of animal tissues and yeast cells. PMID- 17270464 TI - Template matching as a tool for annotation of tomograms of stained biological structures. AB - In recent years, electron tomography has improved our three-dimensional (3D) insight in the structural architecture of cells and organelles. For studies that involve the 3D imaging of stained sections, manual annotation of tomographic data has been an important method to help understand the overall 3D morphology of cellular compartments. Here, we postulate that template matching can provide a tool for more objective annotation and contouring of cellular structures. Also, this technique can extract information hitherto unharvested in tomographic studies. To evaluate the performance of template matching on tomograms of stained sections, we generated several templates representing a piece of microtubule or patches of membranes of different staining-thicknesses. These templates were matched to tomograms of stained electron microscopy sections. Both microtubules and ER-Golgi membranes could be detected using this method. By matching cuboids of different thicknesses, we were able to distinguish between coated and non coated endosomal membrane-domains. Finally, heterogeneity in staining-thickness of endosomes could be observed. Template matching can be a useful addition to existing annotation-methods, and provide additional insights in cellular architecture. PMID- 17270465 TI - Trunk muscle responses to suddenly applied loads: do individuals who develop discomfort during prolonged standing respond differently? AB - Individuals with low back pain or injury (LBP/LBI) have been shown to display altered muscle responses to trunk perturbations; however it is unclear whether these observations are a cause or a result of the LBP/LBI. In this study, a 6.78 kg load was suddenly applied to the hands to perturb the trunk prior to and following a 2-h standing period, during which trunk and hip electromyography (EMG) and centre of pressure (CoP) at the feet were recorded. Seven of the 13 participants developed substantial low back discomfort (LBDiscomfort) during the standing period. These individuals, both pre- and post-standing, showed a greater average number of responsive extensor muscles (3.8 compared to 3.1 in those who did not develop discomfort) and a greater occurrence of extensor muscle response (95-100% of trials) as compared to those who did not develop LBDiscomfort (73-86% of trials). Also, after discomfort developed, these individuals displayed an increased response in their abdominal muscles. This overall increase in trunk musculature activity could either be detrimental by potentially increasing spinal loading leading to LBDiscomfort, or beneficial in that this increased musculature responsiveness may reduce one's likelihood of developing a future LBI through a pathway of increased spine stability. In either case, these responses indicate motor control characteristics that can distinguish the likelihood of an individual developing LBDiscomfort during common tasks such as prolonged standing. PMID- 17270466 TI - Perceiving fear in dynamic body expressions. AB - Characteristic fear behaviour like putting the hands in front of the face and running for cover provides strong fear signals to observers who may not themselves be aware of any danger. Using event-related functional magnetic resonance imaging (fMRI) in humans, we investigated how such dynamic fear signals from the whole body are perceived. A factorial design allowed us to investigate brain activity induced by viewing bodies, bodily expressions of fear and the role of dynamic information in viewing them. Our critical findings are threefold. We find that viewing neutral and fearful body expressions enhances amygdala activity; moreover actions expressing fear activate the temporal pole and lateral orbital cortex more than neutral actions; and finally differences in activations between static and dynamic bodily expressions were larger for actions expressing fear in the STS and premotor cortex compared to neutral actions. PMID- 17270467 TI - A phylogeny of the Lampropeltis mexicana complex (Serpentes: Colubridae) based on mitochondrial DNA sequences suggests evidence for species-level polyphyly within Lampropeltis. AB - The systematic relationships of snakes in the Lampropeltis mexicana complex (L. mexicana, L. alterna, and L. ruthveni) are poorly known despite several taxonomic studies over the last 80 years. Mitochondrial DNA sequences were used to infer the phylogeny of the L. mexicana complex. At least one representative sample from the nine currently recognized species of Lampropeltis was sequenced. Our results suggest that a deep basal split resulted in the divergence of two groups of Lampropeltis, with one group occupying the upland areas of western United States and most of western and central Mexico, and the other northeastern Mexico and the lowland areas of the southern United States. Results also revealed that the L. mexicana complex and Lampropeltis triangulum are polyphyletic, with taxa from both groups nested together in deeply divergent northern and southern clades. These results are incongruent with previous hypotheses of phylogenetic relationships based on morphology, and suggest that morphological characters shared among the various tri-colored Lampropeltis (e.g., hemipenal structure and tri-colored pattern) may be difficult to interpret phylogenetically. PMID- 17270468 TI - Patterns of evolution of mitochondrial cytochrome c oxidase I and II DNA and implications for DNA barcoding. AB - DNA barcoding has focused increasing attention on the use of specific regions of mitochondrial cytochrome c oxidase I and II genes (COI-COII) to diagnose and delimit species. However, our understanding of patterns of molecular evolution within these genes is limited. Here we examine patterns of nucleotide divergence in COI-COII within species and between species pairs of Lepidoptera and Diptera using a sliding window analysis. We found that: (1) locations of maximum divergence within COI-COII were highly variable among taxa surveyed in this study; (2) there was major overlap in divergence within versus between species, including within individual COI-COII profiles; (3) graphical DNA saturation analysis showed variation in percent nucleotide transitions throughout COI-COII and only limited association with levels of DNA divergence. Ultimately, no single optimally informative 600 bp location was found within the 2.3 kb of COI-COII, and the DNA barcoding region was no better than other regions downstream in COI. Consequently, we recommend that researchers should maximize sequence length to increase the probability of sampling regions of high phylogenetic informativeness, and to minimize stochastic variation in estimating total divergence. PMID- 17270469 TI - Transient epileptic opercular syndrome. AB - Ictal transient opercular syndrome is rarely observed in benign epilepsy with centro-temporal spikes in children, and even more rarely in epilepsia partialis continua and symptomatic focal status epilepticus in adults. Here we report the ictal and interictal neuroimaging and electrophysiological findings in an adult female suffering from discontinuous focal status epilepticus presenting as a transient opercular syndrome. This patient was unusual insofar as the discharges were strictly unilateral, i.e., that even with extensive neuroimaging no structural abnormalities could be found. PMID- 17270470 TI - Association between KLOTHO gene and hand osteoarthritis in a female Caucasian population. AB - OBJECTIVE: Osteoarthritis (OA) is a common complex disease with strong heritable components. In this study, we investigated the association between four putatively functional genetic variants in KLOTHO gene, a strong ageing-related gene, and hand OA in a large female Caucasian population. METHODS: Subjects (n=1015, age range 33-74 years) were selected from the TwinsUK Registry. Radiographs of both hands were taken for each individual with standard posteroanterior view. The presence/absence of radiographic OA, osteophyte and joint space narrowing (JSN) was assessed using a standard atlas. Four putatively functional single nucleotide polymorphisms (SNPs) in KLOTHO gene were genotyped using allelic discrimination assay. Association was initially estimated using Pearson's chi(2) or Fisher's exact test at allelic and genotypic levels. The direction and magnitude of significant association were further investigated by robust logistic regression with age as a covariate. RESULTS: We found significant association between SNP G-395A and the presence/absence of radiographic hand OA and osteophyte, but not JSN. Allele G significantly increased the risk for radiographic hand OA and osteophytes with odds ratios (ORs) of 1.44 (P=0.008, 95% confidence interval (CI) 1.09-1.91) and 1.36 (P=0.006, 95% CI 1.09-1.70), respectively. From logistic regression modelling, genotype GG showed more than three-fold increased risk for both radiographic hand OA (OR=3.10, 95% CI 1.10 8.76) and osteophyte (OR=3.10, 95% CI 1.10-8.75) when compared to genotype AA. After adjustment for age, ORs for genotype GG further increased to 4.39 (P=0.006, 95% CI 1.51-12.74) for radiographic hand OA and to 4.47 (P=0.005, 95% CI 1.56 12.77) for osteophytes. CONCLUSIONS: Our results suggest that one variant in KLOTHO gene is associated with the susceptibility of hand OA and appears to act through osteophyte formation rather than cartilage damage. PMID- 17270471 TI - Both exposure to a novel context and associative learning induce an upregulation of AKAP150 protein in mouse hippocampus. AB - A-kinase anchoring protein 150 (AKAP150) is a multi-enzyme signaling complex that coordinates the action of PKA, PKC, and PP2B at neuronal membranes and synapses. We measured levels of AKAP150 protein in the hippocampus 6h after training mice in a contextual fear conditioning paradigm. In contextual fear conditioning mice learn to associate a context with a footshock presentation. Mice were divided in four experimental groups with different training protocols: naive, no footshock exposure, immediate footshock exposure, and footshock 3min after exposure to the context. We found that AKAP150 protein levels were increased upon exposing mice to the novel context independent of the training protocol. However, when the animals were habituated to the experimental context, only mice that learned to associate the context with the footshock showed an upregulation of AKAP150. We suggest that upregulated levels of AKAP150 contribute to processing the exposure to a novel context and associative learning. PMID- 17270472 TI - Superficial venous pathology in the Asian population of South West London--a prospective study. AB - OBJECTIVES: The Asian population of our hospital catchment area represents 6.2% of the total, which is 3.2% higher than the national average, compared to the Caucasian population which comprises 70.2% and is 21.9% lower than the national average. This study aimed to analyse the prevalence and presentation of superficial venous disease (SVD) in the Asian population of South West London. METHODS: A prospectively gathered database of all 481 patients referred by local general practitioners (GP) to the varicose veins nurse specialist over a 24 month period was analyzed. Information was collected on demographics, presenting features, clinical signs, and whether surgical referral was made. RESULTS: Asians presented significantly younger than Caucasians (p<0.0001; unpaired t-test). Caucasians had a significantly higher positive family history than Asians (p 6.0 x 10(11)). RESULT: More than 500 procedures were performed. Four hundred and seventy-nine procedures were included in this evaluation. 21 procedures were not included either because the procedures were not completed due to a donor reaction or lack of data. In 289 of 479 (60.3%) donors, double dose collection was achieved. The average leukocyte contamination was 0.31 x 10(6) in 22 randomly selected products. CONCLUSIONS: The cost of platelet apheresis can be reduced by directing donors with high pre-platelet counts to suitable double dose collection devices in blood centers. PMID- 17270498 TI - A new expertness index for assessment of secondary structure prediction engines. AB - Improvement of prediction accuracy of the protein secondary structure is essential for further developments of the whole field of protein research. In this paper, the expertness of protein secondary structure prediction engines has been studied in three levels and a new criterion has been introduced in the third level. This criterion could be considered as an extension of the previous ones based on amino acid index. Using this new criterion, the expertness of some high score secondary structure prediction engines has been reanalyzed and some hidden facts have been discovered. The results of this new assessment demonstrated that a noticeable harmony has been existed among each amino acid prediction behavior in all engines. This harmony has also been seen between single global propensity and prediction accuracy of amino acid types in each secondary structure class. Moreover, it is shown that Proline and Glycine amino acids have been predicted with less accuracy in alpha helices and beta strands. In addition, regardless of different approaches used in prediction engines, beta strands have been predicted with less accuracy. PMID- 17270497 TI - Hidden symmetries in the primary sequences of beta-barrel family. AB - In this paper, we analyze the symmetries of beta-barrel proteins at both structure and sequence levels by using a modified recurrent quantification analysis. It shows that the structures and sequences have the same two-fold symmetry, although the later diverged considerably. This result may be helpful to understand the mechanism of protein evolution. PMID- 17270499 TI - Predictors of naming decline after dominant temporal lobectomy: age at onset of epilepsy and age of word acquisition. AB - This study examined factors affecting object naming decline in patients who have undergone anterior temporal lobectomy (ATL) and the correlation between age of word acquisition and loss of specific object names postoperatively. The Boston Naming Test (BNT) was used to assess changes in object-naming performance in patients who underwent ATL. Correlation analyses were performed by group (dominant or nondominant ATL) on individual items from the BNT to determine if age of acquisition of object names had an effect on postoperative word loss. The influence of age at onset of seizures on naming decline was examined in the dominant ATL group. Only patients who had undergone dominant ATL experienced significant clinical and statistical declines after surgery. Among the patients who underwent dominant ATL, those with late age at onset of seizures declined significantly more than those with early-onset seizures. When individual object names were examined, age of acquisition of words predicted whether words were lost or gained after surgery. PMID- 17270500 TI - Expression of COX-1 and COX-2 in a clinical model of acute inflammation. AB - Cyclooxygenase (COX) plays an important role in the induction of pain and inflammation as well as the analgesic actions of NSAIDs and coxibs. This study evaluates the expression of the two isoforms COX-1 and COX-2 in a clinical model in which the surgical removal of impacted third molars is used to evaluate the analgesic activity of anti-inflammatory drugs. A 3-mm punch biopsy was performed on the oral mucosa overlying 1 impacted third molar immediately before extraction of 2 impacted lower third molars. After the second tooth was extracted, a second biopsy was performed adjacent to the surgical site either immediately after surgery or 30, 60, or 120 minutes after surgery. RNA was extracted from the biopsy specimens, and RT-PCR was performed to assess mRNA levels of COX-1, COX-2, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH). The RT-PCR products in the biopsy specimens were normalized to G3PDH and compared with baseline. COX-2 mRNA was progressively increased at 30, 60, and 120 minutes after surgery (P<.05); COX 1 mRNA was transiently decreased at 60 minutes during the postsurgical period (P<.05). The results demonstrate peripheral elevation of COX-2 after tissue injury, which may contribute to increased prostaglandin E(2) at the site of injury, pain onset, and the analgesic activity of both nonselective NSAIDs and selective COX-2 inhibitors. PERSPECTIVE: This clinical study uses a physiologically relevant model to determine the time course of expression of COX 1 and COX-2 in acute inflammation of the human oral mucosa. This study furthers our understanding of the contribution of the COX isoforms to acute pain. PMID- 17270501 TI - Proteomic analysis of the venom from the scorpion Tityus stigmurus: biochemical and physiological comparison with other Tityus species. AB - The venom from the Brazilian scorpion Tityus stigmurus was fractionated by high performance liquid chromatography (HPLC) and the corresponding components were used for molecular mass determination using electrospray ion trap mass spectrometry. One hundred distinct components were clearly assigned showing molecular masses from 216.5 to 44,800.0 Da. Fifteen new components were isolated and sequenced, four of them to completion: Tst-3 (similar to Na(+) channel specific scorpion toxins), Tst-17 (a K(+) channel blocking peptide similar to Tc1), Tst beta KTx (a peptide with identical sequence as that of TsTX-K beta toxin earlier described to exist in T. serrulatus venom) and finally a novel proline-rich peptide of unknown function. Among the eleven components partially sequenced were two enzymes: hyaluronidase and lysozyme. The first enzyme has a molecular mass of 44,800.0 Da. This enzyme showed high activity against the substrate hyaluronan in vitro. Amino acid sequence of the second enzyme showed that it is similar to other known lysozymes, with similar molecular mass and sequence to that of bona fide lysozymes reported in public protein data banks. Finally, this communication reports a correlation among HPLC retention times and molecular masses of folded scorpion toxins as well as a comparative structural and physiological analysis of components from the venom of several species of the genus Tityus. PMID- 17270502 TI - Outcome of follow-up colon examination among a population-based cohort of colorectal cancer patients. AB - BACKGROUND & AIMS: The benefit of colonoscopy in the follow-up of colorectal cancer survivors is uncertain, and findings of surveillance colonoscopy are not well-characterized. We sought to estimate survival among colorectal cancer patients according to receipt of a follow-up colon examination and to describe the findings of such exams. METHODS: We studied health maintenance organization enrollees with colorectal cancer who underwent surgical resection. Mortality was estimated by using survival analysis, and findings of colon examinations were determined by review of pathology reports. RESULTS: One thousand two patients were eligible for study; 5-year survival was higher (76.8%) for patients who had at least one follow-up exam than for patients who did not undergo follow-up (52.2%, P < .0001). In multivariate analysis, colon examination remained independently associated with improved survival (hazard ratio, 0.58; 95% confidence interval, 0.44-0.75). Twenty patients (3.1%) were diagnosed with a second colorectal cancer, including 9 cancers detected within 18 months of initial cancer diagnosis. Advanced neoplasia was more common (15.5%) among patients followed up between 36-60 months after diagnosis compared with patients followed up within 18 months (6.9%, P = .02). History of adenomas was associated with advanced neoplasia on follow-up (P = .002). Patients with advanced neoplasia on initial follow-up were at high risk for advanced neoplasia on subsequent examinations (13/16, 81%). CONCLUSIONS: After colorectal cancer resection, patients have a high risk of interval cancers, some of which represent missed lesions at initial diagnosis. Therefore, surveillance colonoscopy within 1 year of initial diagnosis is warranted. After adjusting for key variables, endoscopic surveillance is associated with improved survival. PMID- 17270503 TI - Analytical approaches to determine cytochrome P450 inhibitory potential of new chemical entities in drug discovery. AB - The use of a cassette incubation of probe substrates with human liver microsomes (HLM) - also known as the 'cocktail' approach - is becoming a widely accepted approach to determine the interaction of new chemical entities (NCEs) with cytochrome P450 enzymes (CYP450) in early drug discovery. This article describes two LC-MS/MS-based analytical methods used at the high-throughput (HT) stage and late discovery (LD) stage for analysis of 'cocktail' incubates to analyze the probe metabolites 1'-hydroxymidazolam (CYP3A4), 4'-hydroxydiclofenac (CYP2C9), dextrorphan (CYP2D6), 1'-hydroxytacrine (CYP1A2) and 4'-hydroxymephenytoin (CYP2C19). The analytical methods are advantageous over currently reported methods due to their sensitivity, shorter analyses times (<2 min/sample for the HT method and 4 min/sample for the LD method) and their ability to monitor a unique set of clinically relevant probe metabolites from a biological incubate containing low microsomal protein (0.1mg/mL). The analytical methods employ the same mobile phase, acetonitrile and 0.1% formic acid, under similar LC-MS/MS conditions. In the HT method, the chromatographic method consists of a short robust step-gradient where the probe metabolites are simultaneously and quickly eluted to enhance throughput. The probe metabolites are chromatographically resolved in the LD stage by utilizing a true linear gradient to obtain optimal peak separation. The IC50 data generated by both analytical methods using single incubations versus cocktail incubations for various test compounds are in good agreement (correlation coefficient (r2)>or=0.98). The scientist conducting the analysis is provided with a choice of method selection depending on the stage of the test compound and on whether throughput or minimizing interference from other co-eluting metabolites is the most important criterion. PMID- 17270504 TI - Analysis of alkylphenol and bisphenol A in eggs and milk by matrix solid phase dispersion extraction and liquid chromatography with tandem mass spectrometry. AB - A method based on matrix solid phase dispersion (MSPD) using C18 as dispersant, and a subsequent cleanup step with amino-propyl solid phase extraction cartridges and liquid chromatography electrospray ionization tandem mass spectrometry (LC ESI-MS/MS) has been developed for the simultaneous determination of nonylphenol (NP), octylphenol (OP) and bisphenol A (BPA) in eggs and milk. Recovery studies were performed at different fortification levels. Average recoveries by MSPD varied from 79% of BPA to 98% of NP and relative standard deviations were equal or lower than 15% for egg samples. The average recoveries in milk ranged from 86 to 84% for BPA, 90 to 99% for NP and 82 to 103% for OP and relative standard deviations were equal to or lower than 8%. The limits of detection (LODs) in eggs were 0.10, 0.10 and 0.25 microg/kg for BPA, NP and OP, respectively and LODs for milk were 0.10, 0.05 and 0.10 microg/kg for BPA, NP and OP, respectively. Investigation of the levels in commercial samples indicated that NP was ubiquitous in milk and eggs at levels ranging from 4.24 to 17.60 microg/kg, and the milk samples were more heavily contaminated by NP than were the egg samples. PMID- 17270505 TI - Simultaneous determination of irinotecan (CPT-11) and SN-38 in tissue culture media and cancer cells by high performance liquid chromatography: application to cellular metabolism and accumulation studies. AB - A simple and sensitive HPLC method was developed to simultaneously determine CPT 11 and its major metabolite SN-38 in culture media and cell lysates. Camptothecin (CPT) was used as internal standard (I.S.). Compounds were eluted with acetonitrile-50 mM disodium hydrogen phosphate buffer containing 10 mM sodium 1 heptane-sulfonate, with the pH adjusted to 3.0 using 85% (w/v) orthophosphoric acid (27/73, v/v) by a Hyperclon ODS (C18) column (200 mm x 4.6 mm i.d.), with detection at excitation and emission wavelengths of 380 and 540 nm, respectively. The average extraction efficiencies were 96.9-108.3% for CPT-11 in culture media and 94.3-107.2% for CPT-11 in cell lysates; and 87.7-106.8% for SN-38 in culture media and 90.1-105.6% for SN-38 in cell lysates. Within- and between-day precision and accuracy varied from 0.1 to 10.3%. The limit of quantitation (precision and accuracy <20%) was 5.0 and 2.0 ng/ml for CPT-11 and 1.0 and 0.5 ng/ml for SN-38 in culture media and cell lysates, respectively. This method was successfully applied to quantitate the cellular accumulation and metabolism of CPT-11 and SN-38 in H4-II-E, a rat hepatoma cell line. PMID- 17270507 TI - Expression of bcl-2 in ductular proliferation is related to periportal hepatic stellate cell activation and fibrosis progression in patients with autoimmune cholestasis. AB - AIM: To study bcl-2 expression in ductular proliferation cholangiocytes and hepatic stellate cell activation in liver biopsies from patients with autoimmune cholangitis and primary biliary cirrhosis. MATERIALS AND METHODS: Twenty-four primary biliary cirrhosis patients and 11 autoimmune cholangitis patients were included. Thirty-four females, average age: 52.5+/-12.6 years. We studied the presence of ductular proliferation, cholestasis, florid ductal lesion, granulomata, ductopenia and histologic stage. Patients were classified in primary biliary cirrhosis or autoimmune cholangitis according to antimitochondrial antibodies, antinuclear antibodies, smooth muscle antibody, antiGP210 and antiSP100 autoantibodies. We studied the presence of bcl-2 by monoclonal antibcl 2 antibody (clon 100, BioGenex). The presence of activated (specific antialpha actin antibodies) and independent lobular, periportal and portal hepatic stellate cell was assessed using a semiquantitative scale. RESULTS: Interlobular ducts bcl 2 was seen in 18 (51.4%) patients. Activated periportal hepatic stellate cell correlated with Ludwig's stage (r=0.43; n=35; p=0.01). Ten out of 15 (66.6%) patients with ductular proliferation showed positive interlobular ducts bcl-2 while bcl-2 was negative in 8 out of 20 (40%) patients without ductular proliferation; p<0.05. Bcl-2 positive patients in ductular proliferation showed a more advanced Ludwig's stage (2.33+/-0.77 versus 1.26+/-1.05; p<0.05) and a higher periportal hepatic stellate cell activation index (0.83+/-0.78 versus 0.23+/-0.43; p=0.009). No relationship was found among periportal hepatic stellate cell activation and the presence of florid ductal lesion, cholestasis, granulomata or biliary erosive necrosis. Hepatic stellate cell activation was similar in patients with either autoimmune cholangitis or primary biliary cirrhosis. CONCLUSIONS: Periportal hepatic stellate cell activation seems to play a main role in fibrosis progression in patients with autoimmune cholestasis. Bcl 2 expression in ductular proliferation may promote hepatic stellate cell activation and fibrosis. PMID- 17270508 TI - Effect of ternary phosphate-based glass compositions on osteoblast and osteoblast like proliferation, differentiation and death in vitro. AB - There is currently a need to expand the range of graft materials available to orthopaedic surgeons. This study investigated the effect of ternary phosphate based glass (PBG) compositions on the behaviour of osteoblast and osteoblast-like cells. PBGs of the formula (in mol.%) P(2)O(5)(50)-CaO(50-X)-Na(2)O(X), where X is either 2, 4, 6, 8 or 10, were produced and their influence on the proliferation, differentiation and death in vitro of adult human bone marrow stromal cells (hBMSCs) and human fetal osteoblast 1.19 (HFOB 1.19) cells were assessed. Tissue culture plastic (TCP) and hydroxyapatite (HA) were used as controls. Exposure to PBGs in culture inhibited cell adhesion and proliferation and increased cell death in both cell types studied. There was no significant difference in percentage cell death between the PBGs, which was significantly greater than the controls. However, compared with other PBGs, a greater number of cells were found on the 48mol.% CaO which may have been due to either increased adherence or proliferation, or both. This composition was capable of supporting osteogenic proliferation and early differentiation, and supports the notion that chemical modification of the glass could lead to a more biologically compatible substrate with the potential to support osteogenic grafting. Realisation of this potential should lead to the development of novel grafting strategies for the treatment of problematic bone defects. PMID- 17270509 TI - Efficacy and safety of hyaluronan treatment in combination therapy with home exercise for knee osteoarthritis pain. AB - OBJECTIVE: To assess the efficacy and safety of intra-articular injections of sodium hyaluronate combined with a home exercise program (HEP) in the management of pain associated with osteoarthritis (OA) of the knee. DESIGN: Single-blinded, parallel-design, 1-year clinical study with sequential enrollment. SETTING: University-based outpatient physiatric practice. PARTICIPANTS: Sixty patients (18 men, 42 women; age, > or =50 y) with moderate-to-severe pain associated with OA of the knee. INTERVENTIONS: (1) Five weekly intra-articular hyaluronate injections (5-HYL); (2) 3 weekly intra-articular hyaluronate injections (3-HYL); or (3) a combination of an HEP with 3 weekly intra-articular hyaluronate injections (3-HYL+HEP). MAIN OUTCOME MEASURES: The primary outcome measure was a 100-mm visual analog scale for pain after a 50-foot walk (15.24 m). Secondary measures included the Western Ontario and McMaster Universities Osteoarthritis Index subscales. RESULTS: The 3-HYL+HEP group had significantly faster onset of pain relief compared with the 3-HYL (P<.01) and 5-HYL groups (P=.01). All groups showed a mean symptomatic improvement from baseline (reduction in baseline pain at 3 mo was 59%, 49%, and 48% for the 3-HYL+HEP, 3-HYL, and 5-HYL groups, respectively) that was clinically and statistically significant. There were no between-group differences in the incidence or nature of adverse events. CONCLUSIONS: The combined use of hyaluronate injections with HEP should be considered for management of moderate-to-severe pain in patients with knee OA. PMID- 17270510 TI - Robotic-assisted rehabilitation of the upper limb after acute stroke. AB - OBJECTIVE: To investigate whether early therapy with a novel robotic device can reduce motor impairment and enhance functional recovery of poststroke patients with hemiparetic and hemiplegic upper limb. DESIGN: A single-blind randomized controlled trial, with an 8-month follow-up. SETTING: Neurologic department and rehabilitation hospital. PARTICIPANTS: Thirty-five patients with acute (< or =1 wk of onset), unilateral, ischemic embolic, or thrombotic stroke. INTERVENTIONS: Patients of both groups received the same dose and length per day of standard poststroke multidisciplinary rehabilitation. Patients were randomly assigned to 2 groups. The experimental group (n=17) received additional early sensorimotor robotic training, 4 hours a week for 5 weeks; the control group (n=18) was exposed to the robotic device, 30 minutes a week, twice a week, but the exercises were performed with the unimpaired upper limb. Training by robot consisted of peripheral manipulation of the shoulder and elbow of the impaired limb, correlated with visual stimuli. MAIN OUTCOME MEASURES: The Fugl-Meyer Assessment (FMA) of upper-extremity function (shoulder/elbow and coordination and wrist/hand subsections) to measure each trained limb segment; the Medical Research Council (MRC) score to measure the strength of muscle force during 3 actions: shoulder abduction (MRC deltoid), elbow flexion (MRC biceps), and wrist flexion (MRC wrist flexors); the FIM instrument and its motor component; and the Trunk Control Test (TCT) and Modified Ashworth Scale (MAS). RESULTS: Compared with the patients in the control group, the experimental group showed significant gains in motor impairment and functional recovery of the upper limb after robot therapy, as measured by the MRC deltoid (P< or =.05) and biceps (P<.05) scores, the FMA for the proximal upper arm (P<.05), the FIM instrument (P<.05), and the FIM motor score (P<.01); these gains were also sustained at the 3- and 8-month follow-up. The FMA and MRC wrist flexor test findings did not differ statistically either at the end of training or at the follow-up sessions. We found no significant differences in MAS and TCT in either group in any of the evaluations. No adverse effects occurred and the robotic approach was very well accepted. CONCLUSIONS: Patients who received robotic therapy in addition to conventional therapy showed greater reductions in motor impairment and improvements in functional abilities. Robotic therapy may therefore effectively complement standard rehabilitation from the start, by providing therapeutic support for patients with poststroke plegic and paretic upper limb. PMID- 17270511 TI - The effects of lingual exercise in stroke patients with dysphagia. AB - OBJECTIVE: To examine the effects of lingual exercise on swallowing recovery poststroke. DESIGN: Prospective cohort intervention study, with 4- and 8-week follow-ups. SETTING: Dysphagia clinic, tertiary care center. PARTICIPANTS: Ten stroke patients (n=6, acute: < or =3mo poststroke; n=4, chronic: >3mo poststroke), age 51 to 90 years (mean, 69.7y). INTERVENTION: Subjects performed an 8-week isometric lingual exercise program by compressing an air-filled bulb between the tongue and the hard palate. MAIN OUTCOME MEASURES: Isometric and swallowing lingual pressures, bolus flow parameters, diet, and a dysphagia specific quality of life questionnaire were collected at baseline, week 4, and week 8. Three of the 10 subjects underwent magnetic resonance imaging at each time interval to measure lingual volume. RESULTS: All subjects significantly increased isometric and swallowing pressures. Airway invasion was reduced for liquids. Two subjects increased lingual volume. CONCLUSIONS: The findings indicate that lingual exercise enables acute and chronic dysphagic stroke patients to increase lingual strength with associated improvements in swallowing pressures, airway protection, and lingual volume. PMID- 17270512 TI - The effect of electro-acupuncture on spasticity of the wrist joint in chronic stroke survivors. AB - OBJECTIVE: To quantitatively assess the change in spasticity of the impaired wrist joint in chronic stroke patients after electro-acupuncture treatment. DESIGN: Crossover design. SETTING: University medical center research laboratory. PARTICIPANTS: Seven chronic stroke subjects (age, 63.14+/-7.01y). INTERVENTION: Participants received two 6-week treatment regimens: combined electro-acupuncture and strengthening twice a week, and strengthening twice a week only. Muscle strength and spasticity of the wrist joint were quantified by using the Biodex multijoint System 3 Pro. Electro-acupuncture was given through a commercial electro-acupuncture device. MAIN OUTCOME MEASURES: Velocity sensitivity of averaged speed-dependent reflex torque (VASRT); segmented averaged speed dependent reflex torque (SASRT); Modified Ashworth Scale (MAS) scores; and integrated electromyographic activity of the affected wrist flexors during passive stretch of the affected wrist joint. RESULTS: VASRT was reduced significantly in the combined treatment group (P=.02) after the 6-week period, but not in the strengthening-only group (P=.23); however, no significant immediate effect of electro-acupuncture was observed (P>.05). MAS scores also showed a significant reduction (P<.01). SASRT did not differ significantly across different positions of the joint or across velocity; however, significant differences were present between the 2 treatment groups (P<.05) for each position and at all the velocities except at 20 degrees /s. Integrated electromyographic activity showed a trend for reduction after the combined treatment. CONCLUSIONS: A combination of electro-acupuncture and muscle strengthening exercise for 6 weeks significantly reduced spasticity. The effect of spasticity reduction was consistent across different joint positions and different velocities of passive stretch. PMID- 17270513 TI - A comparison of twice- versus once-weekly supervision during pulmonary rehabilitation in chronic obstructive pulmonary disease. AB - OBJECTIVE: To compare the effects of twice- versus once-weekly supervised pulmonary rehabilitation on exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, randomized, parallel-group study. SETTING: Hospital outpatient physiotherapy department. PARTICIPANTS: Patients with COPD. INTERVENTION: Group 1 (n=46) received 1 supervised exercise session a week and 2 unsupervised sessions; group 2 (n= 45) received 2 supervised exercise sessions a week and 1 unsupervised session for 6 weeks. Patients were assessed at baseline and at 6 weeks, 2 months, and 6 months. MAIN OUTCOME MEASURES: Incremental (ISWT) and endurance (ESWT) shuttle walk tests and Chronic Respiratory Disease Questionnaire (CRDQ). RESULTS: Sixty-six of 91 patients (group 1, n=34; group 2, n=32) completed the 6-week program. There was no significant difference in key outcome measures between the 2 groups (ISWT, 13.50m; 95% confidence interval [CI], -10.06 to 37.15m; ESWT, 72.64s; 95% CI, -96.01 to 241.29s; CRDQ total score, 2.54; 95% CI, -3.16 to 8.24). The results of the ESWTs suggest there may be an interaction between baseline exercise capacity and benefit of pulmonary rehabilitation, with more disabled patients achieving greater benefit if they are supervised twice weekly. Irrespective of group, allocation benefits after pulmonary rehabilitation had almost dissipated by 6 months. CONCLUSIONS: There was no difference in the effectiveness of twice- versus once-weekly supervised pulmonary rehabilitation. This study highlights the need for development of strategies that will maintain the improvement achieved by the initial pulmonary rehabilitation program. PMID- 17270514 TI - Executive function deficits in acute stroke. AB - OBJECTIVES: To establish the frequency of executive dysfunction during acute hospitalization for stroke and to examine the relationship of that dysfunction to stroke severity and premorbid characteristics. DESIGN: Inception cohort study. SETTING: Inpatient wards at a Veterans Affairs hospital. PARTICIPANTS: Consecutive sample of inpatients with radiologically or neurologically confirmed stroke. Final sample included 47 patients screened for aphasia and capable of neuropsychologic testing. Two nonstroke inpatient control samples (n=10 each) with either transient ischemic attack (TIA) or multiple stroke risk factors were administered the same research procedure and tests. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Composite cognitive impairment ratio (CIR), calculated from 8 scores indicative of executive function on 6 neuropsychologic tests by dividing number of tests completed into the number of scores falling below cutoff point, defined as 1.5 standard deviations below normative population mean. RESULTS: Stroke patients had a mean CIR of .61, compared with .48 for TIAs and .44 for stroke-risk-only. Analysis of variance revealed that CIRs of stroke risk-only patients but not TIAs were lower than those of the stroke patients (P=.02). Impairment frequencies were at least 50% for stroke patients on most test scores. The Symbol Digit Modalities Test (75% impairment) and a design fluency measure distinguished stroke from nonstroke patients. CIR was not related to stroke severity in the stroke patient sample, but was related to estimated premorbid intelligence. CONCLUSIONS: Executive function deficits are common in stroke patients. The data suggest that limitations in information processing due to these deficits may require environmental and procedural accommodations to increase rehabilitation benefit. PMID- 17270515 TI - Decreased energy cost and improved gait pattern using a new orthosis in persons with long-term stroke. AB - OBJECTIVE: To measure energy cost and gait analysis in persons with stroke with and without a newly developed orthosis. DESIGN: Immediate and long-term (3wk) intervention (before-after trial). SETTING: University medical center. PARTICIPANTS: Volunteer sample of 27 persons with long-term (range, 0.6-19y) hemiparetic stroke. INTERVENTION: Three-week familiarization to the new walking aid. MAIN OUTCOME MEASURES: Energy cost (per distance walked), preferred walking speed (PWS), and step length. Energy cost was examined in all subjects while walking on a treadmill at 3 different velocities (PWS, PWS+30%, PWS-30%) during 3 different situations (without orthosis, with orthosis, after 3-wk orthosis familiarization). Spatiotemporal aspects of the gait pattern were examined using a 6-m instrumented walkway system. RESULTS: Using the orthosis immediately decreased energy cost in persons with stroke during walking at the PWS (P<.001) and significantly increased walking speed (P<.005) and step length (P<.001). After 3 weeks of familiarization to the orthosis, energy cost at the PWS and at PWS+30% showed further improvement in energy cost (P<.05). CONCLUSIONS: The newly developed orthosis immediately decreases energy cost and improves walking speed and step length in persons with long-term stroke. After only 3 weeks of orthosis familiarization, energy cost shows additional improvement. PMID- 17270516 TI - The effect of cognitive dual tasks on balance during walking in physically fit elderly people. AB - OBJECTIVE: To evaluate the effect on balance of 3 different cognitive dual tasks performed while walking without and with standardization for gait velocity, and measured with both foot placements and trunk movements. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: Fifty-nine physically fit elderly people (mean age, 73.5y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Stride length and time variability measured with an electronic walkway, body sway measured with an angular velocity instrument, and gait velocity. RESULTS: Overall, dual tasks resulted in decreased gait velocity (1.46 to 1.23m/s, P<.001), increased stride length (1.4% to 2.6%), and time variability (1.3% to 2.3%) (P<.001), and had no significant effect on body sway. After standardization for gait velocity, the dual tasks were associated with increased body sway (111% to 216% of values during walking without dual task, P<.001) and increased stride length and time variability (41% to 223% increase, P<.001). CONCLUSIONS: In physically fit elderly people, cognitive dual tasks influence balance control during walking directly as well as indirectly through decreased gait velocity. Dual tasks increase stride variability with both mechanisms, but the increase in body sway is only visible after standardization for gait velocity. The decreased gait velocity can be a strategy with which to maintain balance during walking in more difficult circumstances. PMID- 17270517 TI - Changes in flexed posture, musculoskeletal impairments, and physical performance after group exercise in community-dwelling older women. AB - OBJECTIVE: To determine whether improvements in flexed posture, strength, range of motion (ROM), and physical performance would be observed after 12 weeks of group exercise in older women who because of age are prone to flexed posture and impaired physical function. DESIGN: Pretest-posttest of outcome measures. SETTING: Outpatient academic medical center. PARTICIPANTS: Twenty-one women with thoracic kyphosis of 50 degrees or greater. INTERVENTION: Multidimensional group exercise performed 2 times a week for 12 weeks. MAIN OUTCOME MEASURES: Primary dependent measures of flexed posture included kyphosis, forward head, and height. Other dependent measures included spinal extensor muscle strength; shoulder, hip, and knee ROM; balance; modified Physical Performance Test (PPT); jug test; and gait speed. RESULTS: Baseline kyphosis was 57 degrees +/-5.0 degrees , and age was 72.0+/-4.2 years. There were significant improvements in usual (-6 degrees +/ 3 degrees ) and best kyphosis (-5 degrees +/-3 degrees ) (P<.001), spinal extensor muscle strength (21%+/-13% of peak torque/body weight, P<.001), popliteal angle (right, 7 degrees +/-7 degrees ; left, 9 degrees +/-10 degrees ; P<.001), modified PPT (2+/-2 points, P<.001), and jug test (-1.4+/-1.3s, P<.001). Age and modified PPT at baseline correlated with change in kyphosis (r=0.5, P=.02; r=.42, P=.055, respectively). CONCLUSIONS: Multidimensional group exercise reduced measured kyphosis and improved strength, ROM, and physical performance. This study provides a promising exercise intervention that may improve posture and physical performance in older women with flexed posture. PMID- 17270518 TI - The difference between actual and prescribed weight bearing of total hip patients with a trochanteric osteotomy: long-term vertical force measurements inside and outside the hospital. AB - OBJECTIVE: To determine whether patients load the operated leg at a prescribed weight-bearing target load during postoperative recovery. DESIGN: A descriptive prospective study. SETTING: Orthopedic clinic and patients' homes. PARTICIPANTS: Fifty patients who had undergone total hip arthroplasty (THA) with trochanteric osteotomy. INTERVENTION: Patients were verbally instructed by a physical therapist to perform partial weight bearing at a 10% body weight (BW) target load (n=33) or at a 50% BW target load (n=17). MAIN OUTCOME MEASURES: Mean peak load (%BW) and percentage of patients and mean percentage of steps below, equal to, and above the target load. Weight bearing was measured when patients walked with (condition 1) and without (condition 2) a physical therapist in the hospital and walked at home (condition 3). RESULTS: The mean peak load was significantly higher than the target in the 10% BW group for all 3 conditions (condition 1, 19.2% BW; condition 2, 20.0% BW; condition 3, 26.8% BW). In the 50% BW group, the mean peak load was significantly lower than the target in conditions 1 (28.1% BW) and 2 (32.5% BW). No significant difference in weight bearing was found when walking with or without a physical therapist (change in 10% BW, -0.1% BW; change in 50% BW, -3.17% BW). At home, the mean peak load was significantly larger compared with walking without a physical therapist in the hospital (change in 10% BW, -7.0% BW; change in 50% BW, -11.5% BW). CONCLUSIONS: Partial weight bearing at a specific target load was not achieved by patients with a THA when given verbal instructions. Especially when using a low target load and when walking at home with no supervision of a physical therapist, patients loaded the operated leg higher and more frequently above the target load. Other training methods (eg, biofeedback) have to be evaluated to use as training tools for partial weight bearing at specific target loads. PMID- 17270519 TI - Evaluation of function, performance, and preference as transfemoral amputees transition from mechanical to microprocessor control of the prosthetic knee. AB - OBJECTIVE: To evaluate differences in function, performance, and preference between mechanical and microprocessor prosthetic knee control technologies. DESIGN: A-B-A-B reversal design. SETTING: Home, community, and laboratory environments. PARTICIPANTS: Twenty-one unilateral, transfemoral amputees. INTERVENTION: Mechanical control prosthetic knee versus microprocessor control prosthetic knee (Otto Bock C-Leg). MAIN OUTCOME MEASURES: Stair rating, hill rating and time, obstacle course time, divided attention task accuracy and time, Amputee Mobility Predictor score, step activity, Prosthesis Evaluation Questionnaire score, Medical Outcomes Study 36-Item Short-Form Health Survey score, self-reported frequency of stumbles and falls, and self-reported concentration required for ambulation. RESULTS: Stair descent score, hill descent time, and hill sound-side step length showed significant (P<.01) improvement with the C-Leg. Users reported a significant (P<.05) decrease in frequency of stumbles and falls, frustration with falling, and difficulty in multitasking while using the microprocessor knee. Subject satisfaction with the C-Leg was significantly (P<.001) greater than the mechanical control prosthesis. CONCLUSIONS: The study population showed improved performance when negotiating stairs and hills, reduced frequency of stumbling and falling, and a preference for the microprocessor control C-Leg as compared with the mechanical control prosthetic knee. PMID- 17270520 TI - Recovery of standing balance and health-related quality of life after mild or moderately severe stroke. AB - OBJECTIVE: To examine the physiologic and functional recovery of standing balance and health-related quality of life (HRQOL) in people after mild and moderate stroke. DESIGN: Inception cohort study with evaluations at 1 month and 3 months poststroke. SETTING: Laboratory. PARTICIPANTS: Twenty-nine volunteers who had sustained a stroke. Subjects were categorized into mild and moderate groups. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional balance was assessed (Clinical Outcome Variables Scale [COVS]) and physiologic measures (electromyography, postural sway) were taken when subjects stood quietly on a force platform and when they performed a rapid unilateral arm-raise perturbation. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was administered to evaluate HRQOL. RESULTS: Subjects in the mild group were approaching maximal scores on the COVS (87.7+/-4.1/91) at 3 months poststroke, yet had significant impairment in paretic muscle activation patterns when compared with healthy subjects. Subjects in the moderate group had increased paretic muscle activation over the 2 months, accompanied by significant increases of 10.7+/-5.9 points on the COVS. For both groups, there was significantly less postural sway on the paretic than the nonparetic leg and significant improvements in the SF-36 (physical component) over time. CONCLUSIONS: Subjects recovering from a stroke showed a significant improvement in physical HRQOL and functional and physiologic balance, yet the physiologic balance recovery was not complete even in the mild group. PMID- 17270521 TI - Nutrient supplementation post ambulation in persons with incomplete spinal cord injuries: a randomized, double-blinded, placebo-controlled case series. AB - OBJECTIVE: To examine effects of protein-carbohydrate intake on ambulation performance in persons with incomplete spinal cord injury (SCI). DESIGN: Double blinded treatment with washout and placebo crossover. SETTING: Academic medical center. PARTICIPANTS: Three subjects aged 34 to 43 years with incomplete SCI at C5-T4. INTERVENTIONS: Subjects walked to fatigue on 5 consecutive days. On fatigue, participants consumed 48g of vanilla-flavored whey and 1g/kg of body weight of carbohydrate (CH(2)O). Weekend rest followed, and the process was repeated. A 2-week washout was interposed and the process repeated using 48g of vanilla-flavored soy. MAIN OUTCOME MEASURES: Oxygen consumed (Vo(2); in L/min), carbon dioxide evolved (Vco(2)), respiratory exchange ratio (RER: Vco(2)/Vo(2)), time (in minutes), and distance walked (in meters) were recorded. Caloric expenditure was computed as Vo(2) by time by 21kJ/L (5kcal/L) of oxygen consumed. Data were averaged across the final 2 ambulation sessions for each testing condition. RESULTS: Despite slow ambulation velocities (range, .11-.34m/s), RERs near or above unity reflected reliance on CH(2)O fuel substrates. Average ambulation time to fatigue was 17.8% longer; distance walked 37.9% longer, and energy expenditure 12.2% greater with the whey and CH(2)O supplement than with the soy drink. CONCLUSIONS: Whey and CH(2)O ingestion after fatiguing ambulation enhanced ensuing ambulation by increasing ambulation distance, time, and caloric expenditure in persons with incomplete SCI. PMID- 17270522 TI - Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain injury. AB - OBJECTIVES: To investigate whether the basal plasma amino acid concentrations in patients with traumatic brain injury (TBI) have returned to levels found in healthy controls at about 17 months postinjury and to determine the effect of intake of a mixture of essential amino acids (EAA) on plasma amino acid concentrations in TBI versus healthy controls. DESIGN: Peripheral venous amino acid concentrations in subjects with TBI were compared with concentrations in healthy controls both at rest and for 1 hour after intake of 7g of EAA. SETTING: Postacute brain injury rehabilitation center. PARTICIPANTS: Six men with TBI (age +/- standard deviation, 27+/-6y; months postinjury, 17+/-4) and 6 healthy men (age, 43+/-7y). INTERVENTION: Intake of a drink consisting of 7g of EAA. MAIN OUTCOME MEASURES: Individual and total plasma amino acid concentrations. RESULTS: Total amino acid concentration was about 12% lower in TBI versus controls (P=.022). Valine was reduced by 33% in the TBI group versus controls (P=.003), whereas the other EAA did not differ between groups. After intake of the EAA drink, plasma non-EAA increased to a significantly higher level in controls versus TBI subjects (P=.017). CONCLUSIONS: Plasma total amino acid concentration is still reduced 17 months postinjury in patients with TBI versus healthy controls, mainly because of a lower valine level. This may be of importance for both brain and muscle metabolic functions, and warrant further study. Further, ingested EAA are apparently not as readily converted to non-EAA in TBI patients as in healthy controls, suggesting that in recovery from TBI, certain non-EAA may become provisionally essential. PMID- 17270523 TI - Muscle activation patterns in snapping triceps syndrome. AB - OBJECTIVE: To compare the muscle activation pattern in subjects with and without "snapping triceps syndrome" (dislocation of the medial head of the triceps and ulnar nerve over the medial epicondyle). DESIGN: Controlled study. SETTING: Biomechanics laboratory. PARTICIPANTS: Eight male subjects (9 elbows), with symptomatic snapping triceps and 9 male controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Activation pattern of the 3 triceps heads during active elbow extension at 0 degrees , 45 degrees , 70 degrees , 90 degrees , and 115 degrees of flexion, recorded by fine-wire electromyography. RESULTS: There were no significant differences between subjects and controls in the firing pattern of the triceps heads. The medial head fired first in 6 of 9 symptomatic elbows and in 7 of 9 controls at 90 degrees of flexion, and in 6 of 9 elbows of both subjects and controls at 115 degrees of flexion, positions where snapping typically occurs. There was no significant difference between the groups as to how often the medial head fired maximally. CONCLUSIONS: This study suggests the firing pattern of the triceps heads may not contribute to the pathogenesis of this syndrome. Rather, the authors believe the anatomic position of the medial head causes it to dislocate over the medial epicondyle, often resulting in ulnar neuritis. PMID- 17270524 TI - The effect of poststroke impairments on brachialis muscle architecture as measured by ultrasound. AB - OBJECTIVE: To evaluate the joint angle dependence of brachialis muscle architecture at rest and changes in brachialis muscle architecture during isometric voluntary contractions in people after stroke. DESIGN: The pennation angle and fascicle length of the brachialis muscle were measured in the affected and unaffected sides of people after stroke at 9 different elbow angles ranging from 10 degrees to 90 degrees at the rest condition. Measurements were also carried out at a fixed joint angle of 90 degrees while the subjects were performing isometric muscle contractions at 5 incremental levels of maximal voluntary contraction (MVC) from 20% to 100% of MVC. The data obtained from the affected and unaffected sides of the subjects were compared. SETTING: A research laboratory in a rehabilitation center. PARTICIPANTS: Seven hemiplegic adults after stroke with passive range of motion in the elbow from 10 degrees to 90 degrees and Modified Ashworth Scale score larger than 1 were recruited. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Ultrasonography was used to measure brachialis muscle pennation angle and fascicle length at the rest condition and during isometric contractions. RESULTS: The measured pennation angles and fascicle lengths were found to be joint-angle-dependent in both the affected and unaffected groups at the rest condition. Further comparisons found that the pennation angles of the affected brachialis muscle were significantly larger (P<.05) than the unaffected muscle in the most extended positions (<50 degrees ), whereas the affected fascicle lengths were significantly shorter (P<.05) than the unaffected muscle in most flexed positions (>20 degrees ). As the level of isometric voluntary contraction was increased incrementally from 20% to 100% of MVC, the results showed that pennation angle increased significantly (P<.05) while fascicle length decreased significantly (P<.01) in the unaffected muscle. However, the contraction level has a significant effect only on pennation angle (P<.05) but not on fascicle length in the affected side. In addition, the measured fascicle lengths in the unaffected group were significantly shorter than those in the affected group for isometric contractions above 40% MVC. CONCLUSIONS: Our findings suggest that the architectural parameters of the brachialis muscle in people after stroke are elbow-joint-angle-dependent at the rest condition. In the affected side, pennation angle changed the most when the muscle was in an extension position and fascicle length changed the most in a flexed position when compared with the unaffected side. Immobilization and contracture might cause a shortening of the fascicle and an increase in pennation angle in the affected side. Smaller pennation angle and fascicle length changes in the affected side during isometric contraction might be due to weakness in the muscle after the onset of stroke. PMID- 17270525 TI - Myofascial trigger points in early life. AB - OBJECTIVE: To determine whether latent myofascial trigger points (MTPs) can be identified in healthy infants and in healthy adult subjects. DESIGN: Blind comparison. SETTING: Ambulatory. PARTICIPANTS: A convenience sample of 60 healthy adults and 60 infants (age range, 0-12mo). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: An algometer was used to measure the pressure pain threshold (PPT) on 3 different sites, including a midpoint (assumed to be the MTP site) in the brachioradialis muscle. RESULTS: The mean PPT values at the MTP site were significantly lower than the other sites in the adult muscles. However, no significant differences in PPT values among these 3 sites were found in the infants. Taut bands were found in all the adult muscles but none in the infants. CONCLUSIONS: In the adult subjects, the midpoint of brachioradialis muscle was significantly more irritable than other sites and the midpoint was probably a latent MTP. However, in the infants younger than 1 year old, such a phenomenon could not be observed in this study. It is very likely that the latent MTPs might not exist in early life, but develop in later life. PMID- 17270526 TI - Postherpetic neuralgia involving the right C5 dermatome treated with a cervical transforaminal epidural steroid injection: a case report. AB - A 66-year-old woman presented with 2 weeks of debilitating right upper-limb pain with a vesicular rash over the right C5 dermatome secondary to herpes zoster. Her pain failed to improve with: oral narcotics, divalproex, gabapentin, pregabalin, and topical 2% lidocaine cream. Six weeks postonset, a right C5 transforaminal epidural steroid injection (TESI) under fluoroscopic guidance was performed. Prior to the injection, her numeric pain intensity was rated as 9 to 10/10, and 15 minutes after the injection, it was reduced to 3/10. At 2 weeks, her pain had maintained an intensity of 3/10 and over another 2 weeks had resolved. She remained pain-free 3 months later. In this case, the use of a cervical TESI provided dramatic results in the treatment of debilitating postherpetic neuralgia (PHN). Further investigation is needed to determine the efficacy of TESI in the early management of PHN. PMID- 17270527 TI - Second lumbrical muscle recordings improve localization in severe carpal tunnel syndrome. AB - OBJECTIVE: To determine how often the second lumbrical motor potential is present when the abductor pollicis brevis (APB) motor potential is absent in severe carpal tunnel syndrome (CTS). DESIGN: Prospective study of consecutive patients with severe CTS and an absent motor potential from the APB. SETTING: Single center public hospital-based electromyography lab. PARTICIPANTS: Patients with a clinical diagnosis of CTS who had an absent median sensory response and an absent median motor response to APB on routine nerve conduction testing. Twenty-two hands of 19 patients were examined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Presence and distal latency of motor potential to the second lumbrical. RESULTS: The second lumbrical potential was present in 17 hands (77%). The distal motor latency to the second lumbrical was prolonged in all (mean, 9.1ms; normative value, <4.1ms). CONCLUSIONS: Second lumbrical recordings improve localization in many patients with severe CTS when routine median sensory and motor conduction studies produce no potentials. PMID- 17270528 TI - Do angiotensin-converting enzyme (ACE) inhibitors enhance the effect of exercise rehabilitation in patients with hypertension and ACE DD and DI genotypes? AB - OBJECTIVE: To test whether pharmacologic angiotensin-converting enzyme (ACE) inhibition in carriers of the ACE DD or DI (D, deletion; I, insertion of 287 base pairs) genotypes can simulate the genetic advantage of the II genotype and thereby enhance the conditioning effects of aerobic exercise. DESIGN: Nonrandomized controlled trial. SETTING: Pulmonary institute. PARTICIPANTS: Twelve sedentary men with controlled hypertension (5 with DD genotype, 7 with DI genotype; age, 53+/-7y) treated by ACE inhibitors (study group) and 10 patients (8 men, 2 women; 2 with DD genotype, 8 with DI genotype; age, 54+/-10y) who were treated by other antihypertensive drugs (controls). INTERVENTION: Exercise training. MAIN OUTCOME MEASURES: Training effect was measured by maximal oxygen uptake (Vo(2)max) anaerobic threshold (Vo(2AT)), and the corresponding work rates (WR) (in watts)-WRmax and WR(AT)-before and after 10 weeks of training. RESULTS: Vo(2)max increased by a mean of 10% (200mL/min) and WRmax by 14% (25W) in each group (P<.001). Vo(2AT) and WR(AT) tended to increase more in the study group (Vo(2AT): 10% [186+/-35mL/min] vs 5% [100+/-1mL/min]; P<.006; WR(AT): 19% [19+/ 2W] vs 12% [11+/-3W]; P<.03; respectively). CONCLUSIONS: This study did not show an enhancement of exercise-related conditioning by pharmacologic ACE inhibition among hypertensive patients with ACE DD and DI genotypes, comparable to the advantage conferred by the II genotype. PMID- 17270529 TI - The FIM-SR (self-report) is not the FIM instrument. PMID- 17270531 TI - Pneumatic dilation in treatment of late-onset primary gastric outlet obstruction in childhood. AB - Late-onset primary gastric outlet obstruction in childhood is a rare condition. Only 8 cases of such were reported. Diagnosis should be considered while ruling out mechanical and structural lesions. Up to now, Heineke-Mikulicz pyloroplasty has been the standard treatment. However, we succeeded in treating this condition by using pneumatic dilation. There is no sign of recurrence for 1 year. We propose the etiology, diagnosis, and the relationship between late-onset primary gastric outlet obstruction and esophageal achalasia in childhood. PMID- 17270532 TI - Foreign-body aspiration during microlaryngoscopy: an unusual case of instrument failure. AB - Instrument failure leading to patient morbidity is a recognized surgical complication that has been reported most commonly in the orthopedic and obstetrical literature [Small NC. Complications in arthroscopy performed by experienced arthroscopists. Arthroscopy 1989;4:215-221; Price MV, Molloy S, Solan MC, Sutton A, Ricketts DM. The rate of instrument breakage during orthopaedic procedures. Int Orthop 2002;26(3):185-7; In Y, Bahk WJ, Park JB. Detachment of the tip of a motorized shaver within the knee joint: a complication of arthroscopic surgery. Arthroscopy 2003;19(6):E29-31; Ostrzenski A. An intraoperative method of localizing a missing piece of a broken laparoscopic instrument. Am J Obstet Gynecol 1997;176:726-7]. Instrument failure resulting in airway foreign bodies, to our knowledge, has been reported only once in the English medical literature [Roach JM, Ripple G, Dillard TA. Inadvertent loss of bronchoscopy instruments in the tracheobronchial tree. Chest 1992;101(2):568-9]. This case report describes the aspiration of a fractured portion of a microlaryngeal instrument caused by metal fatigue and corrosion. The authors recommend vigilant and routine inspection of microlaryngeal instruments for early detection of metal corrosion and fatigue. PMID- 17270533 TI - Hirschsprung's disease in an infant with colonic atresia and normal fixation of the distal colon. AB - The coexistence of colonic atresia and Hirschsprung's disease presents a diagnostic and therapeutic challenge. Colonic atresia is quickly recognized, and the majority of patients are diverted shortly after birth. The diagnosis of coincident Hirschsprung's disease usually is made after anastomotic failure after restoration of intestinal continuity. A recent compilation of these patients has suggested that Hirschsprung's disease may be predicted on the basis of nonfixation of the colon distal to the atresia. However, we recently cared for an infant with transverse colonic atresia and total colonic aganglionosis associated with normal orientation and fixation of the distal colon. PMID- 17270534 TI - Concomitant existence of total bowel aganglionosis and congenital central hypoventilation syndrome in a neonate with PHOX2B gene mutation. AB - Hirschsprung's disease (HSCR) is characterized by the absence of intramural ganglion cells in the distal gut, resulting in bowel obstruction shortly after birth. Congenital central hypoventilation syndrome (CCHS) results in hypoventilation, most pronounced during sleep, with relative insensitivity to hypercarbia and reduced insensitivity to hypoxia. Congenital central hypoventilation syndrome with HSCR is a rare condition with variable severity. Both CCHS and HSCR are uncommon and their co-occurrence may suggest a common etiology, probably involving a fault of neural crest development. Recent reports have identified the paired-like homeobox 2B (PHOX2B) gene as the major gene for CCHS and HSCR. We report here an identified PHOX2B gene in a newborn baby who had concurrence of CCHS and total colonic aganglionosis with proximal small bowel involvement. Management of this rare disorder is challenging not only because it presents in newborn stage but also because it has extensive HSCR. Considering the issue of medical futility, the therapeutic and ethical dilemma of this infant was discussed. PMID- 17270535 TI - Pediatric surgeons and gastroesophageal reflux. AB - BACKGROUND/AIMS: Better antacid medications and the introduction of laparoscopy destabilize the indications for fundoplication. This study aims at raising a discussion among pediatric surgeons on these indications, modalities, and the results of this operation. MATERIALS AND METHODS: A total of 252 refluxing children operated between 1992 and 2006 were divided into groups according to predominant symptoms (93 digestive, 47 respiratory, and 68 neurologic) or to comorbidities (27 esophageal atresia, 10 diaphragmatic hernia, 5 abdominal wall defects, and 2 caustic stricture), and the indications, complications, mortality, and long-term results were reviewed. Features of open (n = 135) and laparoscopic (n = 117) approaches were compared, and long-term integrity of the wrap was analyzed using the Kaplan-Meier method. RESULTS: Digestive, respiratory, and neurologic patients had more often laparoscopic plications, whereas all others rather had an open approach. The rate of complications was 22%, and they were more frequent in children operated by laparotomy (P < .05). Median follow up was 51.3 months (range, 6-160). Overall wrap integrity was maintained in 89% of the children, and the proportions for digestive, respiratory, and neurologic groups were 95%, 95%, and 87%, respectively. For esophageal atresia, congenital diaphragmatic hernia, abdominal wall defects, and caustic stricture, they were 72%, 77%, 100%, and 0%, respectively. The functional results were fully satisfactory in 83% of patients. There were 17 deaths (6.7%), but only 3 in the first postoperative month and only 1 related to the operation (0.4%). CONCLUSIONS: Fundoplication is a powerful method of reflux control. It is indicated after failure of medical treatment in gastroesophageal reflux disease and in symptomatic refluxers with some particular comorbidities. Surgery should be offered only after diagnosis has been firmly established, and the indications must remain identical for open and laparoscopic procedures. High technical standards and rigorous report of the results are required for keeping a relevant place of pediatric surgery in the treatment of this disease. PMID- 17270536 TI - Karl Storz Lecture. Skills training in pediatric minimal access surgery. AB - Learning the craft of surgery is central to every surgical program. Although effective, acquisition of skills, particularly that of minimal access surgery in the operating theater, is becoming increasingly difficult. Published data indicate that the early phase of the learning curve could be achieved outside the operating room. However, there is no consensus regarding the optimal training schemes and assessment tools. With an increase in the number of operations performed endoscopically and the number of surgeons performing them, the importance of well-defined and validated training programs cannot be overemphasized. PMID- 17270537 TI - Surgical complications in relation to functional outcomes after ileoanal anastomosis in pediatric patients with ulcerative colitis. AB - BACKGROUND: Significant surgical complications are common in patients with ulcerative colitis who undergo proctocolectomy. We assessed the effects of these complications on the functional outcomes of such patients. MATERIALS AND METHODS: The medical records of 47 consecutive patients who underwent ileoanal anastomosis (IAA; J-pouch IAA, n = 37; straight IAA [SIAA], n = 10) for ulcerative colitis between 1985 and 2004 at a median age of 13.7 years (range, 5.5-19.3 years) were reviewed. Anastomotic leakage and stenosis, fistula, intestinal obstruction (IO), wound complications, pouchitis/enterocolitis (no/once/recurrent), permanent ileostomy, and ultimate diagnosis of Crohn's disease were recorded and correlated with the functional outcome measures of stooling frequency (6 months, 2 years, present), present incidence of soiling, and continence score (range, 0-12). RESULTS: The median postoperative follow-up period was 10 years (range, 1-21 years). Twenty-six (55%) of the 47 patients had surgical complications (J-pouch IAA, 21/37 [57%]; SIAA, 5/10 [50%]; P = nonsignificant). These complications specifically included stenosis of IAA in 4 (9%) patients (SIAA 2), pelvic abscess/sepsis in 4 (9%) patients, late fistula in 4 (9%) patients (SIAA 1), early IO in 8 (23%) patients (SIAA 1), late IO in 14 (27%) patients (SIAA 3), J pouch prolapse in 1 patient, and wound complications in 7 (15%) patients (SIAA 1). Twenty-three (49%) patients had pouchitis, which recurred in 13 (28%). Ileoanal anastomosis stenosis, IO, J-pouch prolapse, wound complications, and pouchitis did not worsen functional outcomes. In 4 patients with pelvic sepsis, early stooling frequency and the continence score were lower than those in the rest of the patients (P < .05). Crohn's disease was ultimately diagnosed in 3 (6%) patients (SIAA 1), 2 of whom (SIAA 1) had permanent ileostomy formation. CONCLUSIONS: Significant surgical complications are common after IAA. Complications do not generally worsen functional outcomes, except in those patients with septic complications or the ultimate diagnosis of Crohn's disease. PMID- 17270538 TI - BAPS UK inflammatory bowel disease surgical practice survey. AB - AIMS: A recent survey of children with inflammatory bowel disease (IBD) identified wide regional variations of care within the UK. The present study was designed to analyse paediatric surgical provision for children with ulcerative colitis and Crohn's disease. METHODS: All UK paediatric surgical centres were contacted to identify surgeons with a subspecialist interest in IBD. A questionnaire was designed to probe specific areas including team working, caseload, and transitional care. Annual consultant caseload was requested for colonoscopy, J-pouch ileoanal anastomosis (IPAA) for ulcerative colitis, and strictureplasty (Crohn's disease). The questionnaire and the accompanying letter were approved by the BAPS Research and Clinical Effectiveness Committee. RESULTS: The response rate from individual centres was 86% (25/29). In 11% of centres, care was shared between 2 consultants. A transitional care clinic was provided by 77% of centres. The median experience with IPAA was 0.9 cases per year of consultant practice (range, 0-3.7), and 12.5% of surgeons had limited experience of revision pouch surgery. The majority have arrangements for joint operating with adult surgeons for IPAA. Forty percent of surgeons reported experience with strictureplasty. Surgical preference for recalcitrant left-side Crohn's colitis favoured segmental resection (60%), compared to subtotal/panproctocolectomy. CONCLUSIONS: Paediatric surgeons use a diversity of surgical management options in IBD. Experience with IPAA is limited for most surgeons. Whether children should undergo elective IPAA independent of experienced adult practitioners, who naturally assume responsibility after transition, requires careful debate. PMID- 17270540 TI - Information on the World Wide Web--how useful is it for parents? AB - AIM: An enormous amount of information about pediatric surgical conditions is available on the World Wide Web (www). Our aim was to ascertain how many parents accessed the www and how useful they found the exercise. METHOD: Over a 2-month period, all parents attending the surgical outpatient clinics were asked to complete a questionnaire regarding Internet use in seeking more information about their child's condition. Parents were able to tick more than one option to the questions. RESULTS: A total of 271 questionnaires were collected and analyzed. There were 53% of responders who had accessed the www. Of this group, 93% used a computer at home, with 60% using the Internet daily. The most popular search engine used was Google (75%). There were 90% who used their child's condition as keyword(s), with 21% using their child's symptoms. The most popular information sought is as follows: Ninety-four percent found the Internet useful. Of this group, 18% considered the information too technical, 18% too distressing, and 2% insufficiently specific. Of the group who did not find the Internet useful (6%), 50% found little or no information, 38% too much information, and 13% thought the details were too technical. Only 25% discussed their findings with their surgeons. Of those who did not, most found that the information was already covered by the surgeons or was irrelevant. CONCLUSION: The Internet is a useful educational tool in teaching parents about their child's condition. Parental use of the Internet is already widespread and may need to be specifically addressed during consultation. The best way to ensure that parents have access to quality and accurate information about their child's condition on the www, hence providing support, is to provide it ourselves. PMID- 17270539 TI - The effect of age on colocalization of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining in enteric neurons in an experimental model. AB - PURPOSE: Cholinergic and nitrergic neurons form 2 main subpopulations of the myenteric neurons, and they have been the targets of detailed morphological investigations in bowel motility disorders. However, little is known regarding the colocalization of neurotransmitters within the same enteric neurons. The aim of this study was to determine the histochemical colocalization of cholinergic and nitrergic neurons in the porcine distal large bowel myenteric plexus from fetal to adulthood. METHODS: Distal large bowel specimens were taken from 6 randomly selected age groups (3 animals in each group) from midway of gestation to adulthood. The myenteric plexus was exposed using whole-mount technique. After nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) staining, cells per ganglion were counted. Then the specimens were stained with acetylcholinesterase (AChE), and the cells that were stained with individual enzymes and with both enzymes were counted. RESULTS: Colocalization of AChE and NADPH-d was seen in all age groups, and it was highest during the mid part of gestation (30%) and decreased steadily thereafter into adulthood (8%). The individual number of NADPH-d- and AChE-positive neurons per ganglion remained constant till 4 weeks of age and significantly increased thereafter into adulthood. CONCLUSION: The use of double-labeling histochemical technique shows for the first time the colocalization of cholinergic and nitrergic activity in a large population of enteric neurons in the late fetal and newborn period. Age related loss of cholinergic and nitrergic colocalization in the myenteric plexus is most likely a maturational process. PMID- 17270541 TI - Social quality of life for adult patients with anorectal malformations. AB - BACKGROUND/PURPOSE: Pediatric surgeons who performed the initial surgery on anorectal malformations (ARM) lose contact with the patients as they become adults. In the present study, we examined 20- to 40-year-old adult patients with a history of surgery for ARM and analyzed them from the points of social quality of life. PATIENTS AND METHODS: Twenty-nine patients with ARM, aged 20 to 40, were surveyed by questionnaire or personal interview. Thirteen with high-type and 9 with intermediate-type anomalies underwent abdominoperineal rectoplasty, and 7 with low-type anomalies underwent perineoplasty between 1965 and 1985. Responses were analyzed from the perspectives of bowel, urinary, and sexual functions and social activity. RESULTS: One third of patients with high- or intermediate-type anomalies occasionally complained of fecal soiling. However, the other patients gained good bowel function and enjoyed occupational or student life without problems. Fecal soiling was the key factor disturbing occupational life, although the problem remained within a socially manageable level. All of the patients with ARM had normal urinary function. Three of the 18 male patients had sexual problems such as erectile or ejaculatory dysfunction because of associated genitourinary anomalies. Nine of the 11 female patients had regular menstruation and the other 2 had irregular menstrual periods. Five female patients were married and 4 of the 5 had children (1-5 children). Modes of delivery were normal vaginal delivery in 8 and cesarean section in 1. Only one of the 5 had a slight sacral anomaly. However, she had no apparent abnormality of bladder function and got through pregnancy and delivery without difficulty. CONCLUSION: One third of adult patients with high- or intermediate-type anomalies after abdominoperineal rectoplasty had some problems in bowel function. Fecal soiling was the key factor that disturbed their occupational life. Most of the patients had normal urinary and sexual functions if they did not have associated genitourinary anomalies and enjoyed social activities. PMID- 17270542 TI - Reoperations in anorectal malformations. AB - AIM OF STUDY: Significant advances have occurred in the management of anorectal malformations, yet many patients still have technical, frequently catastrophic, operative complications that are potentially avoidable. We chose to analyze our experience in patients who have previously undergone a repair which was unsuccessful and required a reoperation, to detect the technical problems that led to complications and to try to establish a set of recommendations to avoid them. METHODS: From a series of 1806 cases of anorectal malformations, 212 were reoperated on after a failed procedure done at another institution. The operative reports of the original procedure were analyzed, as well as our own operative findings, in an attempt to understand the causes of the complications. RESULTS: We found 303 indications for reoperation, with many patients reoperated on for more than 1 problem. Complications requiring reoperation included stricture or acquired atresia of the rectum (87 patients), mislocated rectum (76), recurrent, persistent, or acquired fistula from the rectum to a neighboring urogenital structure, or to the perineal skin (67), persistent urogenital sinus in cases of cloacas (23), rectal prolapse (21), stricture or acquired atresia of the vagina (16), stricture or acquired atresia of the urethra (8), and persistent cloaca (4). The analysis of the original operative report and/or our operative findings indicated that the most common causes of these complications were (a) insufficient rectal mobilization owing to a dissection performed in a wrong plane, or (b) in the presence of or inadequate colostomy located too distally, (c) a tense anastomosis owing to inadequate mobilization, (d) rectal devascularization caused by rectal wall damage, (e) an error in diagnosis because of lack of a distal colostogram, (f) incomplete separation of the rectum from the genitourinary tract, (g) failed attempts to repair a cloaca with a common channel longer than 3 cm, or those with a very high rectum. CONCLUSIONS: The complications we observed usually had a clear explanation. They can be considered preventable as adherence to specific principles in technique avoids them. Key technical maneuvers are discussed to prevent these complications. PMID- 17270543 TI - Familial medullary carcinoma prevention, risk evaluation, and RET in children of families with MEN2. AB - The ability to predict the risk of MEN2 and medullary thyroid carcinoma (MTC) by genetic RET proto-oncogene analysis has provided an essential tool in identifying patients in whom thyroid cancer can be prevented by prophylactic thyroidectomy but emphasizes the need for clear policy guidelines. Children of families with RET cysteine mutations (exons 10, 11, 13, and 16) may develop early metastatic tumours and require prophylactic thyroidectomy. The 918 mutation associated with MEN2B is associated with early aggressive behaviour and distant metastatic spread. This has led to active screening of affected families underlining the need for specific intervention strategies. AIM: To evaluate the risk to children of families with MEN2 and to assess the risk and determine the treatment. METHODS: Twenty-five patients from 10 families with MEN2 phenotypes were screened for RET mutations. Polymerase chain reaction amplification was performed on all 21 exons of the RET proto-oncogene, followed by heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis. Polymerase chain reaction products demonstrating variation in the HEX-SSCP gels were subjected to automated DNA sequencing analysis. RESULTS: Eleven significant RET mutations were detected in affected families. Eight index cases received initial thyroidectomy for established MTC (plus 2 advised). In the family members screened, 3 prophylactic thyroidectomies (2 with early MTC) were performed and a further 2 recommended. An exon 10 C620W missense mutation (the "Janus" gene) was detected in a patient with Hirschsprung's disease plus 1 family member. CONCLUSION: RET analysis of MEN has revolutionized the management of children of families with MEN2 and allowed surgical prediction and prophylaxis to take place. The presence of an exon 10 C620W mutation in association with Hirschsprung's disease was difficult to assess. We suggest possible guidelines for management of families with MTC and the role of genetic testing in their evaluation. PMID- 17270544 TI - Solitary liver cysts in children: not always so simple. AB - AIM: Liver cysts in children are uncommon. Many are simple and solitary and do not require intervention. However, this series demonstrates a broad range of potential pathologies, some of which are life-threatening. METHODS: All children referred to our unit during an 8-year period (1998-2005) and found to have a solitary liver cyst were prospectively recorded. Clinical, radiologic, and pathologic features were analyzed. Children with an isolated extrahepatic choledochal cyst and polycystic disease were excluded. RESULTS: Twenty-one children with a liver cyst were identified. Two had undergone unsuccessful surgical intervention before referral. There were 11 prenatally detected cysts. Median gestational age at detection was 22 weeks (19-35 weeks); only 1 was specifically characterized as a liver cyst prenatally. Six of these required surgery: 2 large simple cysts, 2 intrahepatic choledochal cysts, 1 giant complex biliary cyst causing respiratory distress, and 1 ciliated hepatic foregut cyst. Of the 5 cysts remaining under ultrasound surveillance, 4 decreased in size or resolved. In 10 children presenting between birth and 15.8 years, a liver cyst was diagnosed postnatally: 3 huge cystic mesenchymal hamartomas, 1 type V choledochal cyst, 1 hydatid cyst, and 5 simple cysts. Four of these required surgical resection. Simple cysts tended to be small and could be distinguished from other pathologies using a combination of imaging techniques (ultrasound, magnetic resonance imaging/magnetic resonance cholangiopancreatography [MRCP], radionuclide scan). Only 2 of 12 children with "simple" cysts required surgery for symptoms. However, a wide range of other cyst pathologies were found in 9 children, and although none was malignant, some were life-threatening and 7 required resection. CONCLUSIONS: Simple solitary nonparasitic liver cysts rarely cause symptoms or require surgery, but the pediatric surgeon should be aware of the wide range of other types of liver cyst in children to ensure appropriate treatment. PMID- 17270545 TI - Pediatric pancreatic trauma: predictors of nonoperative management failure and associated outcomes. AB - BACKGROUND: Nonoperative management (NOM) is an accepted treatment of pediatric solid organ injuries and is typically successful. Blunt pancreatic trauma tends to require operative intervention more frequently. We sought to identify predictors of failure of NOM and compare the outcome of operative management against NOM. METHODS: A retrospective analysis was performed from January 1993 to December 2002 of all children with blunt pancreatic injuries from the trauma registries of 7 designated level 1 pediatric trauma centers. Failure of NOM was defined as the need for intraabdominal operative intervention. Injuries were graded I to V, and ductal injury was defined as grades III to V. Parameters included mechanism of injury, injury severity score (ISS), organ grade, Glasgow Coma Scale score, and outcome. Data were analyzed by Fisher exact test and Mann Whitney U test, with mean values +/- SD and significance of P < .05. RESULTS: Pancreatic injuries were present in 173 (9.2%) of 1823 patients. Of these, 43 (26.0% [43/173]) required an operation. Valid morbidity data was obtained in 118 of 173 patients. ISS was significantly higher in all patients treated operatively. Patients with an injury of grade III to V failed NOM more frequently than all patients with pancreatic injury (P =.0169). Length of stay was longer, and the incidence of pseudocysts, drainage procedures, and pancreatitis was higher in NOM patients, although not significant. CONCLUSIONS: Patients with pancreatic injuries had a NOM failure rate of 26.0%. ISS and injury grades III to V were predictors of NOM failure. Patients with pancreatic ductal injury require more aggressive management. PMID- 17270546 TI - Disturbance of retinol transportation causes nitrofen-induced hypoplastic lung. AB - PURPOSE: Retinoids play a key role in lung development. Recent studies suggest that retinoid signalling pathway may be disrupted in the nitrofen model of congenital diaphragmatic hernia (CDH), but the exact mechanism is not clearly understood. We hypothesized that nitrofen interferes with cellular uptake of retinol during lung morphogenesis and therefore designed this study to examine total retinol levels in lung, liver, and serum, and the gene expression of main components of the retinoid pathway in the nitrofen model of CDH. METHODS: Pregnant rats were exposed to vehicle or 100 mg of nitrofen on day 9 of gestation. Term fetuses were divided in control and nitrofen with CDH and without CDH groups. Retinol levels in serum, lungs, and liver were measured using high performance liquid chromatography. Reverse transcriptase-polymerase chain reaction was performed to evaluate the relative amount of cellular retinol-biding protein I, retinal dehydrogenase 1a2 and 1a3 (Aldh1a2 and Aldh1a3), retinoic acid receptors alpha and beta (RARalpha, RARbeta), and retinoid X receptor alpha (RXRalpha) expression in the lung. RESULTS: Total retinol levels in the lungs were significantly lower in both nitrofen with CDH (1.78 +/- 0.37 microg/g) and nitrofen without CDH (1.61 +/- 0.24 microg/g) groups compared with controls (2.43 +/- 0.31 microg/g) (P < .001), whereas serum retinol levels were significantly higher in nitrofen with and without CDH groups (0.77 +/- 0.13 and 0.75 +/- 0.11 microg/g, respectively) compared with controls (0.58 +/- 0.12 microg/g) (P < .001). There was no significant difference in liver retinol levels between the 3 groups. Relative expression of cellular retinol-biding protein I, Aldh1a3, RARalpha, RARbeta, and RXRalpha were significantly up-regulated in the lungs of the nitrofen with CDH group (0.70 +/- 0.15, 3.94 +/- 0.91, 2.15 +/- 0.47, 3.49 +/ 1.00, 1.88 +/- 0.42, respectively) and the nitrofen without CDH group (0.61 +/- 0.14, 3.72 +/- 0.31, 1.66 +/- 0.20, 3.28 +/- 1.02, 1.38 +/- 0.24, respectively) compared with controls (0.43 +/- 0.11, 2.71 +/- 0.47, 0.79 +/- 0.42, 1.85 +/- 0.69, 0.57 +/- 0.22, respectively) (P < .05). CONCLUSION: Our data clearly show that lung retinol storage is decreased in the nitrofen model of CDH. The associated increase in gene expressions of most downstream components of the retinoid signalling pathway may be a feedback reaction to the deficiency of lung retinol. These results suggest that nitrofen acts by interfering with the cellular uptake of retinol during lung morphogenesis resulting in pulmonary hypoplasia in this model. PMID- 17270547 TI - The role of sympathetic innervation in the developing rat gubernaculum. AB - BACKGROUND: Testicular descent occurs in several steps, but the mechanism remains unknown. Recently, sympathetic nerves have been proposed to have a role. This study aimed to see if adrenergic agonists and antagonists affected the neonatal rat gubernacular cremaster sac in organ culture. METHODS: Cremaster sacs were collected from 2-day-old Sprague-Dawley male rats (n = 90) and placed in organ culture with/without (1) calcium chloride (0.45-1.8 mmol/L), (2) rat calcitonin gene-related peptide (CGRP) (714 nmol/L), (3) nifedipine (0.1-100 nmol/L), (4) isopreneline (10 micromol/L), and (5) guanethidine (10 micromol/L). Gubernacula were observed over 2 days for rhythmic peristalsis (>120 beats per minute for >1 minute). RESULTS: Addition of CGRP stimulated rhythmic contractility but only in the presence of calcium, with a dose-response to the level of calcium ions. Contractions induced by CGRP with calcium could be obliterated in a dose-response by nifedipine. Isoprenaline caused some increase in contractions with calcium but less than that seen with CGRP. No augmentation of effect was seen with CGRP and isopreneline together, and the level of contractility was the same with guanethidine. CONCLUSIONS: Calcitonin gene-related peptide is the main effector for contractility of the rat cremaster sac, as long as calcium ions are present. Adrenergic agonists and antagonists had limited effects. Contractility could be inhibited with nifedipine, consistent with CGRP acting via a calcium-dependent pathway. PMID- 17270548 TI - Ureteral reconstruction for retroperitoneal tumors in children. AB - PURPOSE: Removal of solid tumors of the pelvis and abdominal cavity may require resection of an involved ureteral segment. Ureteral stricture can also be a result of intense therapy. We present our experience with urinary reconstruction in this situation. METHODS: A retrospective review of pediatric oncology patients with solid abdominal/pelvic tumors who underwent a ureteral reconstructive procedure was done. Institutional review board wavier was obtained for the review. Patient data were collected on diagnosis, procedures performed, renal function, and follow-up. RESULTS: Thirteen patients were identified: 8 male and 5 female. The mean age at surgery was 10.1 years. The most common reason for surgery was en bloc tumor resection (n = 8) followed by ureteral strictures (n = 3). The Boari flap, Leadbetter-Politano reimplantation, and psoas hitch were the most common procedures preformed. Follow-up studies included measurements of serum urea nitrogen/creatinine levels as well as renal scans to assess functional status; 2 patients had elevated serum urea nitrogen/creatinine levels at follow up. The mean follow-up time was 18 months; 4 patients died-none was secondary to renal complications. There were no local tumor recurrences. CONCLUSIONS: Abdominal and pelvic tumors frequently involve the ureter, and their removal should not necessitate acceptance of poor surgical margins. Complete surgical resection of tumor including involved ureteral segments can prolong survival in patients with extensive abdominopelvic cancers. In another group of patients, ureteral strictures arise secondary to therapy and reconstruction may preserve renal function. PMID- 17270549 TI - The use of conjugated hyperbilirubinemia greater than 100 micromol/L as an indicator of irreversible liver disease in infants with short bowel syndrome. AB - BACKGROUND: The introduction of parenteral nutrition resulted in improved survival of neonates with short bowel syndrome. It is unclear why some may deteriorate to end-stage liver disease (ESLD). Knowledge of when to refer such children for evaluation for transplantation is crucial. A commonly used criterion is conjugated hyperbilirubinemia greater than 100 micromol/L (CB100). OBJECTIVES: The aim of this study is to evaluate if CB100 is a reliable marker for identifying which infants with short bowel syndrome will subsequently develop ESLD. METHODS: All neonates from our short bowel registry (1997-2003) were reviewed. Conjugated hyperbilirubinemia greater than 100 micromol/L was defined as a sustained CB100 for at least 2 weeks with no concurrent sepsis. The sensitivity, specificity, as well as positive and negative predictive values for predicting an outcome of ESLD were calculated. RESULTS: Seventy short gut infants were identified (25 males; mean gestational age of 32.5 +/- 4.9 weeks and weight of 1902 +/- 888 g). Twenty-three patients (33%) developed CB100. Seventeen patients (24%) developed ESLD. Conjugated hyperbilirubinemia greater than 100 micromol/L had a sensitivity of 94% and a specificity of 87% in determining which patients would advance to ESLD. The positive and negative predictive values were 70% and 98%, respectively. The median time from CB100 to ESLD was 60 days (range, 10-365 days). CONCLUSION: A positive predictive value of 70% ensures a safe level of over-triage to the transplant service for assessment; however, the short duration from CB100 to ESLD (60 days) implies a late detection of advanced liver disease, which raises concern about the use of this test in the clinical setting. PMID- 17270550 TI - Jejunal pedicle grafts for reconstruction of the esophagus in children. AB - OBJECTIVE: Reconstruction of the esophagus in children remains a challenge. Although jejunal grafts retain peristaltic activity, large series with long-term follow up are rare. We like to present our experience in a series of 24 children. METHODS: In the period 1988 through 2005, 24 children received an orthotopic jejunal pedicle graft reconstruction of the esophagus. Nineteen had esophageal atresia (18 had no distal fistula; all but 1 had a jejunal graft as a primary procedure), 3 had an extensive caustic stricture, and 2 had a peptic stricture. All strictures had been dilated many times, and peptic strictures had been treated with antireflux surgery as well. Median age at reconstruction was 76 days in the esophageal atresia group. The technique involves a right-sided thoracotomy with preparation of the esophageal ends or resection of the diseased esophagus. At laparotomy, a small pediculated jejunal graft is prepared and placed transhiatally in an orthotopic position in the right chest. RESULTS: All patients survived, and none of the grafts were lost. There were 5 intrathoracic leaks, 4 in the esophageal atresia group and 1 in peptic stricture group, requiring reoperation in 1. In the esophageal atresia group, there was 1 early distal stenosis requiring reoperation. In patients in which the distal esophagus was preserved (esophageal atresia and caustic stricture group), there were always signs of distal functional subobstruction, responding to dilatation in all but 1 patient. Gastroesophageal reflux was not a problem except for 1 patient with esophageal atresia, in whom the distal esophagus was resected because of ongoing distal obstruction with dilatation of the graft. Most patients eat and grow well, and respiratory problems were rare. CONCLUSION: Orthotopic jejunal pedicle graft reconstruction of the esophagus in children is a demanding operation with considerably morbidity but good long-term results. PMID- 17270551 TI - The cumulative incidence of significant gastrooesophageal reflux in patients with oesophageal atresia with a distal fistula--a systematic clinical, pH-metric, and endoscopic follow-up study. AB - BACKGROUND AND AIM: Gastrooesophageal reflux (GER) is common in patients with oesophageal atresia (OA). Complicated GER often manifests itself early after the primary repair (PR) and frequently requires antireflux surgery (ARS). How many patients will be later affected is unknown. We conducted an objective long-term follow-up for the cumulative incidence of OA-associated GER based on pH-metry and histology. MATERIALS AND METHODS: Sixty-one consecutive patients with their native oesophagus, who underwent PR for OA with a distal fistula from 1989 to 2004, were included. These children were grouped according to the Spitz classification with 77% as type I, 20% as type II, and 3% as type III. Significant heart disease, tracheomalacia, or gastric outlet obstruction occurred in 18.0 %, 9.8%, and 17.3% respectively, and a wide gap between esophageal segments occurred in 13.1%. Endoscopy and pH-metry at 1 year were followed up by endoscopy and selective pH-metry at 3, 5, and 10 years. Gastrooesophageal reflux was considered significant (sGER) when a patient underwent ARS, endoscopic biopsies disclosed at least moderate oesophagitis, or when total or preprandial reflux index were greater than 10% or 5%, respectively, with or without long (>5 minutes) reflux periods). Significant GER was considered resolved if, without need for ARS or medication, pH-metry or biopsies returned to normal and the patient was symptomless for at least 3 years. RESULTS: The incidence of sGER/(number of assessed patients) at 6 months, 1 year, 3 years, 5 years, and 10 years was 16.3% (61), 39.3% (61), 44.2% (52), 51.2 % (43), and 44.4% (27). Overall, 28/61 (45.9%) of patients had sGER, and 18/28 (64.3%) patients underwent ARS. In one patient, sGER resolved during the follow-up. CONCLUSION: The number of children with sGER associated with OA more than doubled from 6 months to 1 year after PR. Thereafter, there is a progressive increase in the incidence of sGER with age up to 5 years. Spontaneous resolution of sGER is rare. PMID- 17270552 TI - Abnormal separation of the respiratory primordium in the adriamycin mouse model of tracheoesophageal malformations. AB - BACKGROUND/PURPOSE: Organogenesis relies on temperospatially coordinated signaling systems. The adriamycin rat model provided insights into the dysmorphogenesis of tracheoesophageal malformations. An adriamycin mouse model (AMM) would facilitate the investigation of their molecular pathogenesis. To transfer the knowledge gained from the rat, we describe a histological account of the critical period of organogenesis of these malformations in the AMM. METHOD: CBA/Ca mice were accurately time-mated (n = 18). Dams received intraperitoneal injections of adriamycin (6 mg/kg) (n = 12) or saline control (n = 6) on days 7 and 8. Fetuses were harvested on days 9, 9.5, 10, 11, 12, and 13, resin embedded, and 1-mum sections of the developing foregut were examined. RESULTS: Day 11 control fetuses showed normal separation of the respiratory primordium, with apoptotic bodies at the point of separation. A more caudal point of separation of the distal foregut without apoptotic bodies was found in 4 of 10 AMM fetuses. Day 13 AMM fetuses had dorsal or ventral outpouchings of the foregut, indicating which malformation they would develop. Abnormal branching of the notochord was seen from day 9.5 in AMM fetuses. This was not always associated with abnormal tracheoesophageal development. CONCLUSION: This study confirms that the abnormal observations made in the rat model apply to the mouse. PMID- 17270553 TI - Haemostatic squeezing and purse-string sutures: optimising surgical techniques for early excision of critical infantile haemangiomas. AB - BACKGROUND/PURPOSE: Surgical excision of critical infantile haemangiomas (HMs) is usually delayed until intralesional blood flow spontaneously decreases, but fibrofatty tissue and exuberant skin invariably remain even after total involution. The aim of this study was to describe 2 surgical techniques used for early excision in 50 selected cases of HM defined critical in site or size. METHODS: Among a total of 952 patients affected by HM observed from 1999 to 2005, 50 children (5.2%) were submitted to early surgical removal of the tumour (age range, 6-24 months). In group 1, a technique of lenticular incision and linear closure was used in 34 patients using an original clamp for haemostasis during excision. In group 2, a modified round-block excision and purse-string closure technique was performed in 16 patients. RESULTS: Only 2 patients required transfusion to replace intraoperative blood losses. Infection, delayed wound healing, and cheloids occurred in 3 patients in group 2. Satisfactory cosmetic results have been observed in most cases in both groups at a follow-up ranging from 6 months to 6 years. CONCLUSIONS: The range of indications for early surgical removal of critical HM might be enlarged to achieve earlier the better cosmetic results. A few surgical tricks can minimize intraoperative bleeding and optimise the surgical scar. PMID- 17270554 TI - Treatment of lymphangioma in children: our experience of 128 cases. AB - PURPOSE: The aim of this study is to investigate the optimal treatment for lymphangioma in children by analyzing the effectiveness and complications of treatment modalities. METHODS: We reviewed 128 patients with lymphangioma treated at our institution between 1979 and 2005. Periods of treatment were divided arbitrarily into 2 groups: period I, from 1979 to 1988 (n = 53); and period II, from 1989 to 2005 (n = 75). According to radiological appearance, patients were grouped into 4 types: single cystic (SI; n = 23), macrocystic (MA; n = 11), microcystic (MI; n = 69), and cavernous (CA; n = 25). RESULTS: Sclerotherapy as primary treatment was performed in only 2 patients (3.8%) in period I using bleomycin but increased significantly in period II to 48 patients (64.0%) using OK-432 (P < .01). Nevertheless, primary surgical excision (69/78 patients, 88.5%) was significantly more successful than sclerotherapy (32/50, 64.0%) (P < .01). The following are the locations and types of lesions: head/neck (n = 69; SI, 11; MA, 5; MI, 42; CA, 11), trunk (n = 34; SI, 6; MA, 6; MI, 15; CA, 7), and extremities/other (n = 25; SI, 6; MI, 12; CA, 7). The effectiveness of sclerotherapy in SI, MA, MI, and CA types was 90.9%, 100%, 68.0%, and 10.0%, respectively. Seventeen patients (SI, 1; MI, 8; CA, 8) who received primary sclerotherapy required surgical excision with good outcome. Complications after primary surgical excision were more serious compared with sclerotherapy. CONCLUSION: Sclerotherapy with OK-432 was not as effective as reported in the literature. We recommend OK-432 injection therapy alone for SI and MA types and surgical excision after pretreatment with OK-432 for MI and CA types. PMID- 17270555 TI - Altered serum inhibin b levels in adolescents with varicocele. AB - BACKGROUND/PURPOSE: Different studies have evaluated testicular hormonal dysfunction in adolescent varicocele but with variable results. Recently, inhibin B has been proposed as a marker for spermatogenesis and Sertoli cell function. The aim of the present study was to study in a homogeneous cohort of adolescents inhibin B and other hormones to detect whether untreated varicocele may be associated with any modifications of these factors. METHODS: Sixteen adolescents (mean age, 14.5 +/- 1.0 years), at Tanner stages 4 to 5 with grade II or III left sided varicocele, underwent hormonal evaluation of inhibin B, basal testosterone, and both baseline and GnRH stimulated FSH and LH levels. Thirteen unaffected adolescents of age-matched and pubertal development were used as controls. RESULTS: Patients with varicocele showed a significant reduction in the testicular volume of the affected side (13.3 +/- 4.1 vs 15.8 +/- 4.8 mL; P = .002) and significant reduced levels of inhibin B compared with controls (271.9 +/- 70.2 vs 327.1 +/- 34.9 pg/mL; P = .042). Inhibin B levels were significantly correlated with testes volume (r = 0.62; P = .0097). Other hormonal parameters were similar in both varicocele and control groups. CONCLUSION: Inhibin B is reduced in adolescents with untreated varicocele, and it is positively correlated with testicular volume. This could be an early marker for Sertoli cell damage, with possible implications for spermatogenesis and could represent a new indication for varicocele repair. PMID- 17270556 TI - Does chemical sympathectomy alter the ontogeny of gubernacular migration in vivo? AB - BACKGROUND: Testicular descent occurs in several stages, but the exact mechanism remains obscure. Sympathetic nerves have been proposed to have a role by a possible action on developing cremaster muscle, following observations of sympathetic dysfunction in cremaster from boys with cryptorchidism. This study aimed to see if chemical sympathectomy affected testicular descent in rats. METHODS: Sprague-Dawley dams were injected with 6-hydroxydopamine (days 15-19; 75 microg/kg) or control vehicle alone, and male pups examined at 0 to 10, 20, 30, and 60 days of age. The length of the processus vaginalis was measured and sections taken for histology. RESULTS: No difference in processus vaginalis growth was found between experimental and control groups, both macro- and microscopically. Chemical sympathectomy was confirmed by loss of adrenergic fibres in the adrenal cortex of experimental, but not control, animals. CONCLUSIONS: These studies suggest that sympathetic innervation is not an important part of testicular descent in the rat but does not exclude a pathologic role in undescended testes or effects in humans only. PMID- 17270557 TI - Paraurethral cyst in female newborn: is surgery always advocated? AB - AIM OF THE STUDY: Paraurethral cysts in females are rare, particularly in the neonatal period. Only 49 cases have been previously reported in English literature. The choice of management for this lesion remains controversial. Surgical management has been advocated, but spontaneous regression has also been reported. The aim of the study was to clarify the natural course of paraurethral cysts in female neonates and discuss the proper choice of treatment. PATIENTS AND METHODS: Neonates who presented to our surgical unit with paraurethral cyst over a 5-year period (January 2000 through December 2005) were studied. The "nonoperative strategy" was indicated, and their clinical course and outcomes were examined. RESULTS: Five consecutive patients with paraurethral cysts in female neonates were treated. There have been 5192 female births during the same period, and the incidence of paraurethral cyst was 1 in 1038 female births. None was associated with other anomalies. Clinical examination revealed interlabial cystic mass, which is spherical and yellowish in color, with dilated blood vessel on the anterior surface. It obscured both urethral meatus and vaginal orifice. However, there was no apparent voiding difficulty. These paraurethral cysts spontaneously disappeared at follow-up 76 to 304 days after birth. CONCLUSION: Our data suggest that the number of reported case, being fewer than predicted, suggests that paraurethral cysts in female neonates are unrecognized. Paraurethral cysts are generally characterized by a completely asymptomatic lesion and have a high rate of spontaneously resolution. Thus, surgery (aspiration, marsupialization, or excision) should not be hurried, because natural resolution within a few months is the likely outcome. PMID- 17270558 TI - Large fetal congenital cystic adenomatoid malformations: growth trends and patient survival. AB - PURPOSE: The prognosis for fetuses with large congenital cystic adenomatoid malformations (CCAMs) remains uncertain. This study examined the natural history of large fetal CCAMs managed expectantly at a major referral center. METHODS: A 5 year retrospective review was conducted on fetuses diagnosed with a thoracic lesion (n = 59). Large CCAMs were identified on prenatal imaging and followed longitudinally. Perinatal outcomes were assessed. RESULTS: Twelve (20.3%) fetuses had large CCAMs in the absence of other congenital anomalies. Peak CCAM size occurred at 25.3 +/- 3.6 weeks' gestation. Serial magnetic resonance volumetry demonstrated a trend toward decreasing CCAM mass volume relative to thoracic cavity volume over time. Overall, 6 patients, including 3 with signs of early hydrops, showed a marked regression of their lesions relative to estimated fetal weight. Five fetuses required an emergent intervention postnatally, including extracorporeal membrane oxygenation support (n = 1), cyst aspiration (n = 1), and lung resection (n = 5). Overall survival was 75%, with severe hydrops before 30 weeks seen in all 3 deaths. CONCLUSION: Large fetal CCAMs tend to peak in size at 25 weeks' gestation and are characterized by in utero diminution relative to overall fetal growth. The prognosis for most fetuses with large CCAMs remains quite favorable under careful perinatal management. PMID- 17270559 TI - Antenatally suspected congenital cystic adenomatoid malformation of the lung: postnatal investigation and timing of surgery. AB - BACKGROUND: We have previously reported the outcome of a cohort of cases over a 10-year period with antenatally suspected congenital cystic adenomatoid malformation (CCAM) and have recommended elective surgery within the first year of life for persistent, asymptomatic cases because of the risk of long-term complications. The aims of this study were to document optimal postnatal investigation and timing of surgery. METHODS: Cases were identified using the Oxford Congenital Anomaly Register, theatre records, and histopathology reports. Nineteen cases from 2003 onwards were reviewed with respect to postnatal imaging with chest x-ray and computed tomography scan and timing of surgery. RESULTS: Chest x-ray was poor at detecting CCAM with only 61% sensitivity. Computed tomography scan was 100% sensitive with no false-positive diagnoses. Of the 19 cases since 2003, 13 cases were asymptomatic and had elective surgery. Eight had surgery at 6 months of age or older, and of these, 4 (50%) had evidence of chronic inflammation/infection on histology including 1 case with multiple abscesses found at surgery and 1 case with multiple adhesions. Five cases had surgery at less than 6 months of age and only 1 of these, aged 5.5 months, had evidence of infection present at histology. CONCLUSIONS: All cases of antenatally suspected CCAM should be followed up postnatally and investigated with computed tomography scan. Elective surgery in asymptomatic cases, at around 3 to 6 months of age, is recommended for persistent lesions because of the risk of long-term complications. PMID- 17270560 TI - Reduced expression of aquaporin 5 water channel in nitrofen-induced hypoplastic lung with congenital diaphragmatic hernia rat model. AB - PURPOSE: Pulmonary hypoplasia remains the principal cause of high morbidity and mortality in patients with congenital diaphragmatic hernia (CDH). The precise mechanisms causing lung hypoplasia remains unclear. Aquaporins (AQPs) are reported to constitute a family of water channels that facilitate membrane water permeability in various tissues of animals. Aquaporin 5 has been reported to be an important marker expressed in type I alveolar epithelial cells in late gestation and mediates water transport across the human airway epithelium. We hypothesized that AQP5 is reduced in hypoplastic lungs and therefore designed this study to determine AQP5 expression in normal and hypoplastic lungs. METHODS: Fetal rat lungs of control (n=23) and nitrofen-treated (n=37) dams were harvested on embryonic day (E) 15, E17, E19, and E21. The expression of the AQP5 was analyzed in each lung by real-time reverse transcriptase-polymerase chain reaction. Immunohistochemical studies were performed to evaluate the protein expression level of AQP5. RESULTS: Aquaporin 5 messenger RNA levels on E21 were significantly reduced in lungs from the nitrofen with CDH group (11.8 +/- 2.3) compared with normal controls (23.5 +/- 11.8) and nitrofen without CDH group (26.9 +/- 13.0) (P < .05). Aquaporin 5 immunohistochemistry demonstrated AQP5 strongly expressed at the apical membrane of type I alveolar epithelial cells in the normal and nitrofen without CDH groups. By contrast, the AQP5-positive cells were markedly reduced in hypoplastic lungs in the nitrofen with CDH group. CONCLUSION: Our results show that the expression of AQP5 is down-regulated in hypoplastic lungs with CDH. Down-regulation of AQP5 may result in abnormal pulmonary fluid metabolism in perinatal period and may be one of the mechanisms disturbing the pulmonary development in late stage in the CDH model. PMID- 17270561 TI - Ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation for fetal thoracic masses. AB - PURPOSE: We describe our experience with fetuses diagnosed with life-threatening chest masses who were delivered by ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation (EXIT-to-ECMO). METHODS: The first fetus presented with a cystic mediastinal mass and enlarging echogenic lungs. Bronchoscopic evaluation during ex utero intrapartum treatment (EXIT) revealed complete airway obstruction secondary to a carinal bronchogenic cyst. The second fetus presented with a massive left congenital cystic adenomatoid malformation. The EXIT procedure was performed because of significant mediastinal shift, severe compression of the normal lung parenchyma, and signs of fetal distress. RESULTS: In both cases, extracorporeal membrane oxygenation (ECMO) was initiated while on placental support. The fetuses were then delivered, and a definitive resection of their thoracic lesions was successfully performed. There were no major perioperative complications. Both children made expedient recoveries without significant cardiopulmonary sequelae. CONCLUSION: To our knowledge, this is the first report describing the successful use of EXIT-to-ECMO as a bridge to definitive resection of large chest masses diagnosed in utero. EXIT-to-ECMO is a novel and effective management strategy for stabilizing patients with profound respiratory compromise secondary to congenital thoracic lesions. PMID- 17270563 TI - Surgeons are failing to recognize children with HIV infection. AB - AIM OF THE STUDY: Despite much clinical experience, there are few published accounts of the surgical manifestations of HIV/AIDS in children and still fewer guidelines for the best or most appropriate treatment. Our primary objective was to document the incidence of HIV infection in children who presented with a surgical emergency to a major pediatric surgical unit in South Africa. If possible, we aimed to provide a description of the impact of the disease in a surgical pediatric population and to raise awareness of the mode of presentation of HIV to the pediatric surgeon in a developing nation, now that specific antiretroviral therapies are available. METHODS: This was a prospective observational study of consecutive surgical emergency admissions to the Division of Paediatric Surgery at the University of the Witwatersrand, Johannesburg, South Africa, between April 1 and May 31, 2005. Consent for inclusion in the study was sought in all cases. The clinical profile of children presenting during the study period was recorded. If relevant, permission was sought from the parent/guardian to undertake HIV status testing if this were not already known. MAIN RESULTS: Three hundred ninety-one children were admitted as emergency cases during the study period. Thirty-seven (9.5%) of 391 were excluded, because consent could not be obtained, leaving 354 children. Ages ranged between 1 day and 17 years, with a median age of 3 years. The diagnosis in most was trauma/burns (42%) and abdominal emergencies (27%). Infections occurred in 13% of these patients. Human immunodeficiency virus status was already known in 10 (3%) of 354 patients, and only 18 (5%) of 344 children were tested; of these, 10 (55%) were positive. As expected, the predominant surgical presentation of HIV positive children was sepsis. The prevalence of HIV/AIDS in those children not tested is unknown. CONCLUSION: It is likely that the incidence of HIV/AIDS infection is higher than the 4% identified in our study group. The surgical manifestations in these HIV positive children are dominated by sepsis, often severe in nature and with opportunistic pathogens. Despite increased knowledge about the disease and widening therapeutic opportunities, our results suggest that many children with HIV infection are not being recognized, despite entry into the healthcare system. Prompt recognition and surgical management of the complications of pediatric HIV infection can sometimes result in a good outcome. Further studies are therefore required to define the true incidence of HIV/AIDS infection in children presenting as a surgical emergency case. These patients may benefit from early antiretroviral therapy. Surgeons are well placed to identify children who are HIV positive and should do more to ensure HIV testing and enrollment into antiretroviral treatment programs. PMID- 17270562 TI - Down-regulation of Wnt signal pathway in nitrofen-induced hypoplastic lung. AB - PURPOSE: The pathogenesis of pulmonary hypoplasia associated with congenital diaphragmatic hernia is poorly understood. Recently, it has been reported that Wnt signaling pathway plays a critical role in branching lung morphogenesis. Mice lacking Wnt7b gene die soon after birth because of respiratory failure and display severe lung hypoplasia. Wnt2 gene is expressed in the distal airway during development. To test the hypothesis that Wnt-mediated signaling is altered in nitrofen-induced hypoplastic lungs, we examined the expression of Wnt genes and Wnt target gene, BMP4 in normal and nitrofen-treated lungs. MATERIALS AND METHODS: Fetal rat lungs of normal (n = 24) and nitrofen-treated (n = 24) dams were harvested on embryonic day (E)15, E17, E19, and E21. The expression of GATA6, the Wnt genes (Wnt7b, Wnt2), and BMP4 was analyzed in each lung by real time reverse transcription polymerase chain reaction. RESULTS: The gene expression of Wnt7b, Wnt2, and BMP4 on E15 was significantly reduced (P < .05) in lungs from nitrofen-treated animals compared with normal lungs. The expression level of GATA6, which has been reported to transactivate Wnt7b expression, was also significantly reduced (P < .05) in lungs from the nitrofen group. CONCLUSION: Our results provide evidence for the first time that the Wnt signaling pathway is down-regulated in nitrofen-induced hypoplastic lungs in the early stages of lung development. Decreased expression of GATA6 may account for the down-regulation of Wnt signal pathway. These data suggest that the down regulation of Wnt signaling pathway may disrupt branching lung morphogenesis, resulting in pulmonary hypoplasia in the nitrofen rat model of congenital diaphragmatic hernia. PMID- 17270565 TI - Evaluation of the portal vein after duodenoduodenostomy for congenital duodenal stenosis associated with the preduodenal superior mesenteric vein, situs inversus, polysplenia, and malrotation. AB - A male infant weighting 2970 g with total situs inversus, polysplenia, malrotation, duodenal stenosis, and complex cardiac anomalies, was admitted to our hospital. At 4 days of age, he underwent surgery that revealed a blood vessel passing over the duodenum from the mesenterium to the porta hepatis. A loose overbridging duodenoduodenostomy was performed to prevent compression of the vessel. The cardiac anomalies were corrected, and he could eat unrestricted diets. At the age of 1 year and 3 months, a 3-dimensional computed tomographic scan demonstrated that the vessel on the duodenum was the superior mesenteric vein (SMV), and it formed the portal vein with the splenic vein at the porta hepatis. Further, the scan revealed no compression of the SMV at the anastomosis. Doppler ultrasonography revealed a normal portal blood flow of 118.6 mL/min. This report describes the junction between the SMV and the splenic vein in a patient who had the SMV passing over the duodenum from the mesenterium. Correctly, patients previously diagnosed with a preduodenal portal vein could have a preduodenal SMV. The loose overbridging duodenoduodenostomy had advantages not only in passage of the anastomosis but also in maintenance of the portal blood flow for the congenital duodenal obstruction with the preduodenal SMV. PMID- 17270567 TI - 2 children with acute abdominal pain and diarrhea. PMID- 17270568 TI - Medical disorders affect health outcome and general functioning depending on comorbid major depression in the general population. AB - OBJECTIVE: The objective of this study was to compare health-related quality of life (HR-QoL), disability/work productivity, and health care utilization in a variety of medical disorders with and without comorbid major depressive disorder (MDD) in the general population. METHODS: Twelve-month MDD (Composite International Diagnostic Interview) diagnosis was determined among 4181 participants from a community sample. Medical diagnoses (respiratory, cardiovascular, allergic, endocrine/metabolic, gastrointestinal, and neurological diseases) were made after medical examination. HR-QoL was evaluated with the MOS SF-36. Outpatient doctor visits and disability/work productivity were assessed by self-report. RESULTS: Comorbid MDD was associated with a lower SF-36 mental summary score in all medical diagnoses and with a lower physical summary score in comorbid allergic and neurological disorders. The number of coexisting medical disorders was strongly related to lower physical and mental summary scores in cases without comorbid depression. The number of outpatient doctor visits increased by 42% when any of the medical disorders without comorbid MDD was present, and comorbid MDD was associated with a further 24-42% increase, depending on the medical disorder. Comorbid MDD was strongly associated with lower full-time working status (37.1% with MDD vs. 51.0% without MDD) and with a significant increase in disability days (45%) in the presence of any medical disorder. CONCLUSIONS: Findings have consequences for diagnostic and treatment procedures, as well as in relation to the importance of the number of medical disorders in future studies. PMID- 17270569 TI - Course and predictors of medically unexplained pain symptoms in the general population. AB - OBJECTIVE: The objective of this study was to explore the course and the predictors of clinically significant medically unexplained pain symptoms (MUS pain) within the 6 months preceding the interviews at baseline and on follow-up in the general population. METHODS: A Norwegian general population study of 605 persons interviewed with the Composite International Diagnostic Interview Somatoform Section was conducted in 1989/1990 (baseline), and 421 persons (69.6% response rate; 242 women and 179 men) were reinterviewed in 2000/2001 (follow up). Cases of recent MUS-pain compared with those at baseline were assessed on follow-up. Four blockwise logistic regression analyses were undertaken to find predictors (such as stressful life events, living alone, depression and anxiety, and physical morbidity) for recent MUS-pain in 2001. RESULTS: A small "stable" group of recent MUS-pain sufferers (8% of all reinterviewed and 33.6% of those with recent MUS-pain at baseline) was evident. In this group almost all were women. In addition to female gender being a significant (P<.05) marker of recent MUS-pain (which gives a twofold-higher risk compared with men), only depression- not the occurrence of prior recent MUS-pain--remained a significant (P<.05) predictor in the final model, increasing the likelihood of having recent MUS-pain by threefold. CONCLUSION: The prognosis of MUS-pain is relatively good, except for a small group (mainly women) that is prone to chronicity. Clinicians should examine for depression when confronted with MUS-pain patients and should be aware of the twofold-higher risk in women for persistent MUS-pain over a long time. PMID- 17270570 TI - Do illness perceptions predict health outcomes in primary care patients? A 2-year follow-up study. AB - OBJECTIVE: Little is known about whether illness perceptions affect health outcomes in primary care patients. The aim of this study was to examine if patients' illness perceptions were associated with their self-rated health in a 2 year follow-up period. METHODS: One thousand seven hundred eighty-five primary care patients presenting a new or recurrent health problem completed an adapted version of the illness perception questionnaire and the Medical Outcomes Study 36 Item Short-Form Health Survey (SF-36) at baseline and 3, 12, and 24 months' follow-up. Linear regressions were performed for (1) all patients, (2) patients without chronic disorders presenting physical disease, and (3) patients presenting medically unexplained symptoms (MUS). RESULTS: Negative illness perceptions were associated with poor physical and mental health at baseline. They most strongly predicted changes in health status at follow-up for the whole group of patients. Patients presenting with MUS had more negative illness perceptions and lower mental and physical components subscale of the SF-36 scores at all time points. CONCLUSIONS: Patients' perception of a new or recurrent health problem predicts self-reported physical and mental health up to 2 years after consulting the general practitioner and offers an obvious starting point for addressing nonbiomedical aspects of illness. PMID- 17270571 TI - Childhood adversities experienced by working-age migraine patients. AB - OBJECTIVE: The objective of this work was to study associations between childhood adversities and migraine. METHODS: This is a case-control study of individuals drawn from the Finnish Population Register comprising four age groups: 20-24, 30 34, 40-44, and 50-54 years. Altogether, 21,101 individuals responded to postal questionnaire (response rate=40%). The subjects were asked whether a doctor had told them that they have or have had migraine. They were then requested (through six questions) to think about their childhood adversities. One randomly selected age-matched and sex-matched control for comparison was selected for every patient (n=4046). RESULTS: Among migraine patients, 76.8% were women. Each of the six childhood adversities was more common among migraine patients than among controls. In conditional logistic regression analysis for matched-pairs data, long-lasting financial difficulties in the family, a family member having been seriously or chronically ill, serious conflicts in the family, and parents having divorced remained statistically significant after adjusting for education, state of health, and depression. Odds ratios varied between 1.22 and 1.29. CONCLUSION: Our findings suggest that social factors during childhood are associated with migraine. PMID- 17270572 TI - Exploring the role of sleep and coping in quality of life in fibromyalgia. AB - OBJECTIVE: The objective of this study was to explore the effect of sleep and coping on health-related quality of life in fibromyalgia syndrome (FMS). METHODS: Patients diagnosed with FMS (N=101) completed the Positive and Negative Affect Schedule, the Pittsburgh Sleep Quality Index, the COPE, and the Medical Outcomes Study--Short-Form Health Survey for the previous month. RESULTS: Poor sleep quality was reported by 99% of participants. Sleep quality was significantly predictive of pain, fatigue, and social functioning in patients with FMS. Active coping, planning, acceptance, and seeking instrumental and emotional social support were not predictive of health outcomes in FMS. However, the use of restraint coping was predictive of poorer physical functioning. CONCLUSION: Sleep quality has significant implications for health-related quality of life in FMS. The use of coping strategies contributed little to the models' ability to predict health outcomes in FMS. Interventions designed to improve sleep quality may help to improve health-related quality of life for patients with FMS. PMID- 17270573 TI - The characteristics of fatigue in an older primary care sample. AB - BACKGROUND: Primary care studies of younger adults have reported fatigue to be common and etiologically heterogeneous with both physical and psychological associations. This has led to considerable debate about whether fatigue may present independently of psychological disorder. Somatic symptoms in older people have been assumed to be almost entirely physical in origin. AIMS: To determine the characteristics of fatigue and its relationship with psychological disorder in older primary care attenders. METHOD: Ambulatory primary care patients aged 60 years and over completed self-report questionnaires and psychiatric interview at baseline and at 12 months. RESULTS: The overall prevalence of fatigue was 27.4% with most, but not all, cases being comorbid with psychological disorder. Psychological disorder (OR, 8.43; 95% CI, 2.98-23.88) was a greater predictor of fatigue than physical illness (OR, 4.74; 95% CI, 1.63-13.85). Neither a tendency for fatigue to evolve into psychological disorder, nor vice versa, was observed longitudinally (overall kappa, 0.68; P<.001). CONCLUSIONS: Fatigue is common in older primary care attenders and is not associated with physical illness alone. Despite the high rate of comorbidity with psychological disorder, independent and longitudinally stable forms of fatigue did present. The overall findings suggest that while fatigue does overlap with psychological phenomena, there may also be distinct forms of fatigue. PMID- 17270574 TI - Somatoform dissociation and somatosensory amplification are differentially associated with attention to the tactile modality following exposure to body related stimuli. AB - OBJECTIVE: Body-focused attention is regarded as an important maintaining factor for somatoform illness, although there is limited empirical evidence pertaining to this hypothesis. This study was conducted to assess whether individual differences in somatoform dissociation and somatosensory amplification were associated with biased attention towards the tactile modality, particularly following exposure to threatening body-related stimuli. METHODS: Forty-eight nonclinical participants completed the Somatoform Dissociation Questionnaire (SDQ 20; a proxy measure of somatoform symptomatology), the Somatosensory Amplification Scale (SSAS), and a modality bias task. The task consisted of a series of body-relevant or body-irrelevant (scene) picture stimuli, half of which were threatening and half were neutral, followed by target stimuli in either the visual or the tactile modality. Participants judged the location of each target stimulus, and performance data were used to calculate the degree to which participants were biased towards the tactile modality following each of the picture types. RESULTS: Participants in the high SDQ-20 group (defined by median split) showed a significant increase in tactile bias when responding to targets occurring 250 ms after the presentation of threatening body-relevant stimuli only. This effect was not observed for the low SDQ-20 group. Scores on the SSAS correlated negatively with tactile bias for both threatening and neutral body relevant stimuli at 250 ms. CONCLUSIONS: Individuals with a tendency to experience somatoform symptoms focus more on stimuli in the tactile modality immediately following exposure to threatening body-relevant information. In contrast, self-reported somatosensory amplification appears to be associated with attention away from the tactile modality rather than with increased tactile focus. PMID- 17270575 TI - Development of an emotional processing scale. AB - OBJECTIVE: The objective of this study was to report on the development and preliminary psychometric evaluation of an emotional processing scale, a 38-item self-report questionnaire designed to identify emotional processing styles and deficits. METHODS: An initial item pool derived from a conceptual model and clinical observations was piloted on clinical and community samples (n=150). The resulting 45-item scale was administered to patients with psychological problems, psychosomatic disorders, and physical disease, and to healthy individuals (n=460). Exploratory factor analysis was used to explore the underlying factor structure. RESULTS: Maximum likelihood factor analysis yielded an eight-factor solution relating to styles of emotional experience (Lack of Attunement, Discordant, and Externalized), mechanisms controlling the experience and expression of emotions (Suppression, Dissociation, Avoidance, and Uncontrolled), and signs of inadequate processing (Intrusion). Internal reliability was moderate to high for six of eight factors. Preliminary findings suggested satisfactory convergent validity. DISCUSSION: Overall, the psychometric properties of this scale appear promising. Work is in progress to refine the scale by incorporating additional items and by conducting further psychometric evaluations on new samples. PMID- 17270576 TI - Beliefs about sleep in disorders characterized by sleep and mood disturbance. AB - OBJECTIVES: Maladaptive sleep beliefs play an important role in primary insomnia, but their role in other disorders with concomitant sleep disruption has rarely been explored. Thus, this study investigated the link between insomnia and sleep beliefs in five groups (N=422): primary insomnia (PI), good sleepers (GS), fibromyalgia (FM), major depressive disorder (MDD), and Community Sleep Clinic patients with comorbid insomnia and mood disturbance (CSC). METHOD: Groups were compared on the Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16) scale. RESULTS: Unlike the GS group, the MDD, FM, and CSC groups had elevated DBAS-16 scores that were similar to, or more pathological than, those of primary insomnia sufferers. Only some of the differences were removed after controlling for depression. CONCLUSION: Like primary insomnia patients, other sleep-disturbed patient groups have problematic sleep beliefs. Depression was not sufficient to account for all elevations in beliefs. The presence of maladaptive sleep beliefs in these patients suggests that belief-targeted treatment might be helpful in alleviating sleep complaints. PMID- 17270577 TI - Effectiveness of a meditation-based stress management program as an adjunct to pharmacotherapy in patients with anxiety disorder. AB - OBJECTIVE: The objective of this study was to examine the effectiveness of a meditation-based stress management program in patients with anxiety disorder. METHODS: Patients with anxiety disorder were randomly assigned to an 8-week clinical trial of either a meditation-based stress management program or an anxiety disorder education program. The Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory, and the Symptom Checklist--90-Revised (SCL 90-R) were used to measure outcome at 0, 2, 4, and 8 weeks of the program. RESULTS: Compared to the education group, the meditation-based stress management group showed significant improvement in scores on all anxiety scales (HAM-A, P=.00; STAI state, P=.00; STAI trait, P=.00; anxiety subscale of SCL-90-R, P=.00) and in the SCL-90-R hostility subscale (P=.01). Findings on depression measures were inconsistent, with no significant improvement shown by subjects in the meditation-based stress management group compared to those in the education group. The meditation-based stress management group did not show significant improvement in somatization, obsessive-compulsive symptoms, and interpersonal sensitivity scores, or in the SCL-90-R phobic anxiety subscale compared to the education group. CONCLUSIONS: A meditation-based stress management program can be effective in relieving anxiety symptoms in patients with anxiety disorder. However, well-designed, randomized, and controlled trials are needed to scientifically prove the worth of this intervention prior to treatment. PMID- 17270578 TI - Cardiovascular responses across stressor phases: the match of gender and gender role identification with the gender relevance of the stressor. AB - OBJECTIVE: To test the hypothesis that cardiovascular responses across stressor phases (anticipation, stressor, recovery) are higher when gender or gender-role identification match with the gender relevance of the stressor than in case of a mismatch and gender irrelevance which are not supposed to differ. METHODS: In a double-blind design, 151 healthy women and men were assigned to the Cold Pressor Test with feminine, masculine, or gender-irrelevant introductions. RESULTS: The pattern of responding was vascular [high on systolic blood pressure (SBP), diastolic blood pressure (DBP), and total peripheral resistance (TPR), and relatively low on heart rate, stroke volume, and cardiac output] across stressor phases. SBP, DBP, and TPR responses supported the gender match hypothesis, although men showed higher TPR responses to irrelevance than to mismatch. DBP and TPR responses supported the gender-role identification match hypothesis. CONCLUSION: The match-mismatch-irrelevance paradigm contributes to the understanding of gender differences in stress responses and related health risks. PMID- 17270580 TI - The relationship between alexithymia and perinatal depressive symptomatology. AB - OBJECTIVE: The purpose of this study was to examine the relationship between alexithymia and perinatal depressive symptoms and the stability of the alexithymia construct in a sample of low-income, predominantly Latina women during pregnancy and the early postpartum period. METHODS: Seventy-seven pregnant women completed self-report questionnaires and were classified as "high risk" or "low risk" for developing a major depressive episode based on a history of depression and/or current high depressive symptom scores. Measures included the Toronto Alexithymia Scale, the Center for Epidemiological Studies Depression Scale, and the Maternal Mood Screener, and were completed during pregnancy and at postpartum month 2. RESULTS: Alexithymia was positively associated with depressive symptoms during pregnancy and early postpartum. Women at high risk for depression had significantly higher alexithymia levels than low-risk women during pregnancy but not during postpartum. Alexithymia and depressive symptoms were independently and strongly correlated across the ante- and postpartum periods. Hierarchical regression analyses indicate that alexithymia scores at postpartum were predicted by alexithymia scores during pregnancy, above and beyond the variance explained by the depressive symptom scores during pregnancy and postpartum. CONCLUSION: Alexithymia is positively correlated with depressive symptoms during the perinatal period and is a stable phenomenon. PMID- 17270579 TI - Interferon-alpha-induced depressive symptoms are related to changes in the cytokine network but not to cortisol. AB - OBJECTIVE: Proinflammatory cytokines have the potential to activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and HPA axis hyperactivity is also encountered in depression. Therefore, the induction of depressive symptoms by interferon-alpha (IFN-alpha) may be mediated by changes in the cytokine network and the HPA axis. METHODS: In 17 hepatitis C patients undergoing IFN alpha treatment, depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). In addition, serum cytokine concentrations were measured. Saliva was collected five times over the course of a day in order to assess daily average cortisol (DAC) and awakening response. Assessments were carried out at baseline and six later time points after starting treatment. RESULTS: During treatment, the increases in the MADRS were significantly and positively correlated with soluble interleukin (IL)-2 receptor, tumor necrosis factor alpha (TNF-alpha), and IL-6. There were no significant associations between the DAC or cortisol awakening response with the MADRS score. CONCLUSION: Results suggest a clear connection between IFN-alpha-induced depressive symptoms and cytokine concentrations, but not cortisol. PMID- 17270581 TI - Alexithymia and global psychosocial functioning: a study on patients with skin disease. AB - OBJECTIVE: The relationship between alexithymia and psychosocial functioning has been investigated in a few studies using indirect measures of adaptation. We aimed at directly evaluating the relationship between alexithymia and global psychosocial functioning, as measured by a standardised scale. METHODS: A large, consecutive sample of dermatological inpatients (N=545) completed the 20-item Toronto Alexithymia Scale and the Skindex-29 and were administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders and the Global Assessment of Functioning (GAF) scale. RESULTS: Multiple regression analysis was used to control for likely determinants of psychosocial functioning such as age, sex, education, burden of skin symptoms, and psychiatric morbidity. The GAF score was associated with psychiatric morbidity (beta=-.63, P<.001), alexithymia (in particular, the difficulty identifying feelings subscale) (beta=-.19, P<.001), and burden of skin symptoms (beta=-.07, P<.05). CONCLUSION: Given the well-known association between poor psychosocial functioning and several behavioural risk factors for health, our study may provide a further reason for clinicians to pay attention to alexithymic features among their patients. PMID- 17270582 TI - What happens in the course of body exposure? Emotional, cognitive, and physiological reactions to mirror confrontation in eating disorders. AB - OBJECTIVE: Though body exposure seems to enhance outcome in cognitive-behavioural therapy of anorexia and bulimia nervosa, the underlying mechanisms are still unknown. METHODS: Participants with eating disorders (ED; n = 21) and normal controls (NC; n = 28) were exposed to their own bodies in front of a mirror for 40 minutes under standardized conditions. Emotions, cognitions, and saliva cortisol were assessed every 10 minutes during body exposure. Heart rate and skin conductance were recorded continuously. RESULTS: ED showed higher negative emotional and cognitive responses to body exposure compared to NC, whereas no group differences were found for physiological reactions. In the course of body exposure, the extent of negative emotions and cognitions decreased significantly with medium effects for emotions and low effects for cognitions. Physiological parameters remained stable during the task. CONCLUSION: Body exposure is a promising technique to overcome negative body-related emotions, but additional cognitive techniques are necessary. PMID- 17270583 TI - Identifying the eating disorder symptomatic in China: the role of sociocultural factors and culturally defined appearance concerns. AB - OBJECTIVES: This study evaluated the extent to which eating disorder symptomatic Chinese adolescents and young adults could be differentiated from demographically similar peers on the basis of their sociocultural experiences and appearance perceptions. METHODS: Forty-two students who endorsed all criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition eating disorder diagnosis on the Eating Disorder Diagnostic Scale [Stice E, Telch CF, Rizvi SL. Development and validation of the Eating Disorder Diagnostic Scale: a brief self-report measure of anorexia, bulemia, and binge-eating disorder. Psychol Assess 2000;12:123-31] and 42 less symptomatic classmates completed measures of perceived social pressure, teasing, social comparison, negative affect, and concern with facial features. RESULTS: Symptomatic participants reported significantly more social pressure/teasing, appearance comparison, and concern with facial appearance than their less symptomatic peers, although groups did not differ in average levels of negative affect. In a jackknife discriminant classification analysis using these five predictors, 76.2% of the symptomatic group and 81.0% of the comparison group were correctly classified. Within the symptomatic group, 95% of respondents who reported either full or partial criteria for bulimia nervosa or binge-eating disorder were correctly identified compared to 59.10% of those who endorsed all criteria for eating disorders not otherwise specified related to anorexia nervosa. CONCLUSIONS: This is the first study to link appearance-related social pressure and social comparison as well as appearance concerns not directly reflecting body size or weight with increased eating disorder symptomatology among young people from the People's Republic of China. PMID- 17270584 TI - Controversies in consultation-liaison psychiatry. PMID- 17270586 TI - Pharmacotherapeutic uses of hormones. AB - This article reviews the use of hormones and related molecules in pharmacology. Examples of hormones in the treatment of specific diseases is presented, including those where normal physiologic levels of hormones are restored, and others where supraphysiologic levels are used to achieve a therapeutic effect. Examples of the abuse of hormones are also described. PMID- 17270587 TI - Hypovitaminosis D and morbid obesity. AB - There is scarce and flawed data regarding vitamin D status in morbidly obese patients. More often than not, vitamin D deficits have been linked with bariatric surgery, not considering that the deficit may well precede surgery. Moreover, several pathophysiologic mechanism might explain, in part, vitamin D deficits. Conversely, the association between vitamin D deficits and secondary hyperparathyroidism in morbidly obese patients has been reported before and after bariatric surgery. Taking into account the elevated prevalence of vitamin D deficits in morbidly obese patients, its associated comorbidity, and the efficacy and low cost of its treatment to restore normal serum values of 25-OH-vitamin D, it seems advisable to recommend routine monitoring of serum calcium, phosphorus, and 25-OH-vitamin D levels in morbidly obese patients and to implement calcium and vitamin D supplementation whenever necessary. PMID- 17270588 TI - A cascade of events -- obesity, metabolic syndrome, and type 2 diabetes mellitus in youth. AB - Increased rates of obesity among youth in the last several decades also have led to the emergence of several health problems. Insulin resistance and metabolic syndrome are direct outcomes of increasing obesity rates, which, in turn, lead to the emergence of type 2 diabetes mellitus in youth. Nurses are well positioned to intervene with individual youth and populations at risk to interrupt the cascade of events that lead from obesity to severe health problems. PMID- 17270589 TI - Diabetes update: injectable therapies for type 2 diabetes: practical applications for older adults with pancreatic failure. AB - The goal of therapy for older adults who have type 2 diabetes and pancreatic failure is to provide the best management program that meets his/her individual needs and lifestyle. The goals are to maintain blood sugar control, but more importantly, to prevent complications and to provide the patient with a better quality of life through a more natural metabolic state. Decisions about when to add insulin to the regimen, the goals of therapy, what types of insulin to use, and how to monitor response are based on the pathophysiologic mechanisms, which ensures overall treatment success. The information that patients gather and record will assist in decisions about therapy that maximize the benefits and eliminate the problems that patients often experience when therapies are modified without a careful plan. PMID- 17270590 TI - Isolated use of vibration perception thresholds and semmes-weinstein monofilament in diagnosing diabetic polyneuropathy: "the North Catalonia diabetes study". AB - Several systems are used for the diagnosis of diabeticpolyneuropathy (DPN). We analyzed the isolated use of vibration perception thresholds (VPTs) or monofilament (MF) for the diagnosis of DPN. A group of 400 patients who had type 2 diabetes was selected from the North Catalonia Study Group. A clinical neurologic evaluation was performed based on three categories of the San Antonio Consensus. Neurothesiometer and quantitative tuning fork explored VPT, and MF was assessed by Olmos and Michigan Diabetic Neuropathy Score (MDNS) criteria. The use of VPT and MF showed a high specificity and low sensitivity. MF, by MDNS criteria, was more sensitive and specific, and showed more accurate positive and negative predictive values. The predicted probability of DPN diagnosis was higher with a tuning fork evaluation. PMID- 17270591 TI - Diabetes and depression: a review of the literature. AB - Depression affects millions of people in the United States. Drugs used to treat depression can lead to weight gain, which could predispose a person to type 2 diabetes. Also, certain medications that may be used to treat depression with psychotic features can lead to metabolic syndrome and new-onset diabetes. Diabetes is another chronic health care condition that affects millions of people in the United States. Diabetes is the leading cause of nontraumatic amputations and a leading cause of blindness. Both conditions can result in a lower quality of life. Clinicians face challenges in treating either condition, but can face greater ones when the conditions occur together. This article reviews the literature concerning depression and diabetes. PMID- 17270592 TI - Primary hyperparathyroidism, insulin resistance, and cardiovascular disease: a review. AB - The presentation of primary hyperthyroidism (PHPT) has changed substantially in the last decade. Before the introduction of routine calcium measurement in most automated biochemistry serum analyzers, it usually was diagnosed after renal and bony lesions already were present. Nowadays, its presentation is practically asymptomatic. Nevertheless, the cardiovascular morbidity and mortality of mild to moderate forms of PHPT reportedly are increasing. Individuals who have mild to moderate forms of PHPT have an increased risk for enduring cardiovascular disease, arterial hypertension, left ventricular hypertrophy, myocardial and valvular calcifications, altered vascular reactivity, and cardiac conduction. Finally, they also reveal alterations in carbohydrate metabolism, insulin resistance, dyslipidemia, and body composition. PMID- 17270593 TI - Hypogonadal hypogonadism and osteoporosis in men. AB - In recent years, osteoporosis in men has become increasingly recognized as an important clinical and public health problem. Many similarities exist in various aspects of osteoporosis in men and women, but this article focuses on the sex difference, bone biology, epidemiology, and consequences of fractures. Although maintenance of bone integrity depends on the action of sex hormones in both sexes, menopause is a much more obvious indicator of estrogen deficiency than is the subtle decrease of testosterone in aging men. This often leads to delay and neglect of diagnosis. The need to identify and screen men at a particular risk for osteoporosis, as when hypogonadism is induced for treatment of prostate cancer, has become important. PMID- 17270594 TI - Pheochromocytoma: challenges in diagnosis and nursing care. AB - Pheochromocytomas are catecholamine-secreting tumors arising from chromaffin cells of the sympathoadrenal system, which includes the adrenal medulla and sympathetic ganglionic tissue. The effects of catecholamine excess cause potentially fatal symptomologies and end-organ damage if not diagnosed and treated. If diagnosed and removed surgically, most of these patients can be cures. Pheochromocytomas are rare and affect from two to eight per million people. There are 800 deaths in the United States annually as a result of complications. Of patients who have pheochromocytomas diagnosed at autopsy, 75% died suddenly from myocardial infarction or cerebral vascular catastrophe. Challenges in diagnosis, tumor location, and treatment are considerable. PMID- 17270595 TI - Diabetes and thyroid disease: nursing care to improve outcomes for patients living in poverty. AB - A primary goal of nurses providing care for persons who have diabetes mellitus or thyroid disease is improving their health outcomes. For persons who have diabetes and thyroid disease and live in poverty, improving the care process, and ultimately health outcomes, must include the nurse's understanding of poverty. The purpose of this article is to provide nurses with a basic understanding of the resource issues, "hidden rules," and characteristics that are associated with persons who live in poverty. Most importantly, some basic strategies to improve the health outcomes of patients who have diabetes or thyroid disease and live in poverty are provided. PMID- 17270596 TI - Rapid and reversible alterations in thyroid function tests in dehydrated patients. AB - Dehydration commonly leads to hypovolemia and hemoconcentration. Changes in thyroid hormone-binding proteins secondary to hemoconcentration profoundly affect total serum thyroid hormone concentrations. The authors sought to determine the acute effects of mild to moderate dehydration on thyroid hormone levels/thyroid function tests and its reversibility upon rehydration. Total thyroxine, total triiodothyronine, free thyroxine, and the free-thyroxine index decreased significantly after hydration, in parallel with the decrease in extra cellular fluid volume status markers. Triiodothyronine-resin uptake increased after hydration. Thyrotropin levels decreased by 8% after hydration. Hypovolemia leads to simultaneous alterations in extracellular fluid volume markers and thyroid hormone serum concentrations that reverse rapidly upon rehydration. This constitutes, by itself, a distinct and new clinical entity. PMID- 17270598 TI - Targeted molecular therapy for renal cell carcinoma. PMID- 17270599 TI - DNA methylation of GSTP1 as biomarker in diagnosis of prostate cancer. PMID- 17270600 TI - Outcome of buccal mucosal graft urethroplasty for long and repeated stricture repair. AB - OBJECTIVES: To evaluate the efficacy of one-stage buccal mucosal tubed graft in long and repeated urethroplasty. METHODS: Thirty-four patients with long and repeated strictures of the urethra underwent buccal mucosal urethroplasty from 2000 to 2003. For all patients, one-stage buccal mucosal tubed graft urethroplasty was performed by releasing and extracting the fibrous tissue around the stricture, harvesting buccal mucosa from the inner cheek, tubing the graft, and interposing it in the defect. The urethral catheter was removed 3 weeks postoperatively. Suprapubic drainage was in place until urethral patency was confirmed by antegrade cystourethrography. The patients were followed up with clinical history and symptom reporting, urinalysis and culture, periodic uroflowmetry, ultrasonography, and cystourethrography at 1, 3, and 6 months and yearly thereafter. The urinary flow rates before and after surgery, postvoid residual urine volumes, restricture rates, and incidence of incontinence, erectile dysfunction, fistula, and diverticulum were assessed. RESULTS: The procedure was technically successful in all patients. The mean operative time was 150 minutes. During 28 months (range 12 to 39) of follow-up, the success rate was 76.5%. Restricture occurred in 5 patients during the first year postoperatively. Urethrocutaneous fistula, erectile dysfunction, and diverticulum occurred in 2, 1, and 1 patient, respectively. The mean urinary flow rate and postvoid residual urine volume improved significantly. Patient satisfaction was good. CONCLUSIONS: Buccal mucosal grafts are tough, resilient, easy to harvest, and leave no scar. They appear to be an optimal substitute for anterior and posterior long urethral strictures in repeated urethroplasty. PMID- 17270603 TI - High-power holmium:yttrium-aluminum-garnet laser for percutaneous treatment of large renal stones. AB - OBJECTIVES: To assess the efficacy and safety of high-power holmium-yttrium aluminum-garnet (YAG) laser lithotripsy for percutaneous nephrolithotomy in patients with large renal stones. METHODS: We retrospectively reviewed the charts of 87 patients who underwent 91 percutaneous nephrolithotomy procedures at our hospital from April 2004 to June 2005, during which a holmium-YAG laser with a self-made fiber guider was used for lithotripsy. Of the 91 procedures, 51 were performed with the maximal power output set at 3.0 J in patients with a renal stone size of 3 cm or larger (group 1). The other 40 procedures were performed with the maximal power set at 2.0 J in patients with a renal stone size of less than 3 cm or with ureteral stones (group 2). RESULTS: The average stone size was 5.4 cm in group 1, and the stone-free rate was 61.4% after a single procedure. The average operation time was 108 minutes in group 1 and 93 minutes in group 2. The average postoperative hospital stay was 5.7 days in group 1 and 5.9 days in group 2. Two patients in group 1 and one in group 2 required blood transfusions after the procedure. Seven patients (13.7%) in group 1 and two (5.0%) in group 2 experienced a urinary tract infection after the procedure. No statistically significant difference in procedure time, postoperative hospital stay, blood transfusion rate, or postoperative urinary tract infection rate was found between the two groups. CONCLUSIONS: The results of our study have shown that using a high-power holmium-YAG laser is safe and effective in the treatment of large renal stones. PMID- 17270606 TI - Emergency ureteroscopic management of ureteral stones: why not? AB - OBJECTIVES: To describe a single-center experience in the emergency ureteroscopic management of ureteral stones. METHODS: We retrospectively considered the data from 144 patients (mean age 49.6 years, range 23 to 82) who had had obstructive ureteral stones and had undergone emergency ureteroscopy with stone retrieval. Intracorporeal pneumatic lithotripsy was performed when necessary. At the end of the procedure, a ureteral catheter was systematically left in place in 100 patients (69.4%) and removed within 24 hours. In the remaining 44 patients, a double-J stent was preferred and was removed within 30 days, depending on the clinical course. Stone-free status was defined as the complete absence of fragments at 1 month of follow-up. RESULTS: The calculi were more frequently localized in the distal ureter than in the proximal one (90.3% versus 9.7%, respectively). The overall mean stone diameter was 9.1 mm (range 5 to 20). The overall stone-free rate was 92.4%. A greater stone-free rate was obtained in those with stones less than 10 mm (95.8%) than in those with stones larger than 10 mm (89%, P = 0.002). Similarly, a significantly better outcome occurred for those with stones located in the distal ureter (94.6%) than for those with stones in the proximal one (71.4%, P = 0.004). The overall complication rate was 4.2%. The mean hospital stay was 2.5 days (range 1 to 7). CONCLUSIONS: In our experience, emergency ureteroscopy in cases of obstructive ureteral stones proved to be safe and effective. It has the main advantage of offering both immediate relief from pain and stone fragmentation. Additional extensive studies are warranted to corroborate these findings. PMID- 17270610 TI - Analysis of impact of body mass index on outcomes of laparoscopic renal surgery. AB - OBJECTIVES: As the prevalence of obesity increases in the United States, it has become more important to assess its impact on surgical outcomes. We evaluated the significance of obesity on laparoscopic radical nephrectomy (LRN) and laparoscopic partial nephrectomy (LPN). METHODS: This was a prospective database study evaluating patients who underwent either LRN or LPN from October 2002 to January 2006. Patients were divided into five groups as determined by the World Health Organization body mass index (BMI) classification: less than 25.0, 25.0 to 29.9, 30.0 to 34.9, 35.0 to 39.9, and 40.0 kg/m2 or more. Demographic (age, tumor size, American Society for Anesthesiologists score), operative (estimated blood loss, operative time, open conversion), and postoperative (complications, hospital stay, margin status) data were compared. RESULTS: Of 239 patients who had undergone LRN or LPN during the study period, 146 underwent LRN and 85 underwent LPN. Of the 239 patients, 42% were obese. No statistical significance was determined for estimated blood loss, operative time, hospital stay, number of open conversions, or complications. However, a trend toward increased operative time and intraoperative complications was determined using linear and logistic regression analyses. CONCLUSIONS: Laparoscopic renal surgery is safe in overweight and obese patients and may be the surgical management of choice in this subset of patients. However, obese patients should be warned that their degree of obesity may be associated with increased difficulty of surgery as reflected by a trend toward longer operative times and more intraoperative complications. PMID- 17270609 TI - Expression of survivin in renal cell carcinomas: association with pathologic features and clinical outcome. AB - OBJECTIVES: To investigate the expression of survivin in renal cell carcinoma and try to define its association with certain pathologic features and the clinical outcome. METHODS: The tissue samples from 85 consecutive renal cell carcinoma specimens were obtained from patients who had undergone radical or partial nephrectomy. The mean follow-up was 45 months (range 3 to 60). Immunohistochemical staining of the paraffin sections of the pathologic sample was performed using monoclonal antibody for survivin with the standard avidin biotin-peroxidase technique. The mean expression rate of survivin was assessed by inspection of at least five microscopic fields at 400x magnification. Expression of survivin was considered positive when more than 10% of the cancer cells in the microscopic fields demonstrated immunostaining. The degree of expression of survivin was compared with the clinicopathologic features. RESULTS: Survivin was expressed in 67 (79%) of 85 samples. Immunostaining for survivin was demonstrated in the cytoplasm of tumor cells and in vascular endothelial cells. A significant increase in survivin expression was associated with increased T stage (P = 0.044), increased tumor grade (P = 0.0013), and low recurrence-free survival (P = 0.046). Multivariate Cox regression analysis revealed that survivin expression is an independent prognostic parameter (P = 0.021) in renal cell carcinoma. CONCLUSIONS: The results of this study suggest that survivin-mediated inhibition of apoptosis is associated with progression and recurrence of renal cell carcinoma. Thus, survivin is a useful independent prognostic marker for this condition. PMID- 17270611 TI - Laparoscopic partial nephrectomy in obese patients. AB - OBJECTIVES: To report our experience with laparoscopic partial nephrectomy in obese (body mass index greater than 30 kg/m2) patients compared with a contemporary cohort of nonobese patients. METHODS: From August 1999 to December 2004, 140 obese (group 1) and 238 nonobese (group 2) patients underwent laparoscopic partial nephrectomy at our institution. We compared the demographics, operative data, and perioperative complications of these two groups. RESULTS: Group 1 had a significantly greater incidence of hypertension and diabetes. In groups 1 and 2, respectively, the mean estimated blood loss was 310 mL (range 50 to 1500) and 249 mL (range 50 to 2500), the mean operating time was 3.4 hours (range 2.5 to 6) and 3.4 hours (range 1.5 to 6), and the mean warm ischemia time was 31 minutes (range 15 to 51) and 32 minutes (range 12 to 60). Intraoperative complications occurred in 8 patients (5.7%) in group 1 and 20 (8%) in group 2 (P = 0.19), with a blood transfusion rate of 6% and 3%, respectively (P = 0.42). The postoperative complication rate was not significantly different between the two groups (13% versus 9%, P = 0.77). The mean hospital stay was 2.8 days (range 1 to 8) for group 1 and 3.5 days (range 1 to 32) for group 2. Retroperitoneal access was associated with a shorter operative time and hospital stay in both groups. CONCLUSIONS: Laparoscopic partial nephrectomy was performed safely in obese patients, with a perioperative complication rate similar to that of nonobese patients. The retroperitoneal approach was associated with a shorter operative time and hospital stay in the obese and nonobese patients. PMID- 17270612 TI - Complications of laparoscopic living donor nephrectomy and their management: the UCLA experience. AB - OBJECTIVES: Because of the shortage of cadaveric kidneys, laparoscopic living donor nephrectomy (LLDN) has become a more common option for transplant recipients. The complication rate has been reported at 6.4% to 16.5%. We present the initial University of California, Los Angeles experience with the complications and their management during LLDN. METHODS: From January 2000 to December 2005, a single surgeon performed 300 consecutive LLDNs at our institution. A committee of urologists, nephrologists, and support staff approved each donor before surgery. After LLDN was completed, the patients received 30 mg of ketorolac intravenously every 6 hours until discharge. We reviewed the intraoperative and postoperative complications and their management at our institution. RESULTS: Three patients required open conversion, for an overall conversion rate of 1%. Two of the three conversions were a result of a major vascular complication (0.6%). The first major vascular complication resulted from an endovascular stapler malfunction during transection of an accessory left renal artery. The second vascular complication was a Veress needle injury to the left common iliac artery. Three postoperative major complications (1%) occurred, including 1 case of rhabdomyolysis and 2 cases of chylous ascites. Also, 7 minor postoperative complications (2.3%) occurred. Our overall complication rate was 4%. No patients died, and the mean hospital stay was 1.1 days. CONCLUSIONS: Our results have shown that LLDN is a safe procedure associated with low morbidity and a quick recovery. Appropriate patient selection is essential to ensure the safety of this procedure. PMID- 17270613 TI - Oncologic outcome of hand-assisted laparoscopic radical nephrectomy. AB - OBJECTIVES: To evaluate and compare the oncologic outcome of hand-assisted retroperitoneoscopic radical nephrectomy (HALS) with that of open radical nephrectomy. METHODS: The clinical and follow-up data of 123 patients with localized renal cell carcinoma who underwent HALS were retrospectively compared with those of 70 patients who underwent open radical nephrectomy. RESULTS: No significant differences were found in operating time, complication rates, or transfusion rates between the HALS and open groups. The estimated blood loss was significantly less in the HALS group. The median follow-up period was 41.0 months for the HALS group, significantly shorter than that for the open group (74.5 months). The 3 and 5-year disease-free survival rate for the HALS and open groups was 94% and 92% and 93% and 91%, respectively. The 3 and 5-year cancer-specific survival rate for the HALS and open groups was 96% and 92% and 98% and 94%, respectively. No significant differences were found in the disease-free and cancer-specific survival rates between the two groups. In the HALS group, no significant differences were found in the disease-free survival rate between those undergoing surgery by less-experienced surgeons who had performed laparoscopic nephrectomy on 10 cases or less and those undergoing surgery by more experienced surgeons. CONCLUSIONS: The oncologic outcome of HALS did not differ much from that of the open approach. Also, the experience of the surgeon did not affect the oncologic outcome. However, extended follow-up is necessary to assess the true oncologic efficacy of HALS. PMID- 17270614 TI - Recovery of detrusor function after urethral botulinum A toxin injection in patients with idiopathic low detrusor contractility and voiding dysfunction. AB - OBJECTIVES: To investigate the effect of urethral botulinum A toxin (BoNT-A) injection on idiopathic low detrusor contractility and the correlation of this effect with baseline urodynamic parameters. METHODS: Twenty-seven patients with idiopathic low detrusor contractility received urethral injection of BoNT-A. Videourodynamic studies were performed at baseline and after treatment. Recovery of detrusor contractility was defined as an increase in detrusor pressure and maximal flow rate and reduced postvoid residual urine volume. The therapeutic results and changes in urodynamic parameters were compared between patients with and without recovery of detrusor contractility. RESULTS: The recovery of detrusor contractility after urethral BoNT-A injection occurred in 13 patients (48%). Patients with recovery of detrusor contractility had baseline data characterized by normal bladder sensation during bladder filling combined with a poor relaxation or hyperactive urethral sphincter activity. In contrast, patients without recovery of detrusor contractility had poor bladder sensation and a nonrelaxing urethral sphincter. Patients with baseline characteristics of low detrusor contractility combined with poorly relaxed or hyperactive urethral sphincter activity had better results than those with true detrusor underactivity. Of the 13 patients with recovery of detrusor contractility, 5 had a long-term therapeutic effect without the need of repeat urethral injection of BoNT-A for more than 1 year of follow-up. CONCLUSIONS: Patients with detrusor underactivity with normal bladder sensation combined with a poor relaxation or hyperactive urethral sphincter were significantly more likely to recover normal detrusor function. Neuromodulation of the hyperactive urethral sphincter by urethral BoNT-A is the likely mechanism for this therapeutic effect. PMID- 17270617 TI - Process for development of multicenter urodynamic studies. AB - OBJECTIVES: To describe our experiences with a continuous quality improvement process for the standardization of multicenter urodynamic studies (UDSs) in a multi-institutional network. Multicenter UDSs can have considerable variations in testing procedures, training, equipment, and reviewer biases. METHODS: A quality control process was developed that included protocol development, certification of urodynamic testers, central review to assess compliance with protocol and quality, protocol modifications, standardization of equipment and signal configuration, development of an electronic signal repository, and the development of UDS Interpretation Guidelines. RESULTS: We describe our experience and process in the development and implementation of a standardized UDS protocol in a multicenter surgical trial for stress urinary incontinence. The process included our protocol development, quality control measures, standardization processes, electronic signal repository, and the need for UDS Interpretation Guidelines. A urodynamic testing procedures protocol was implemented successfully by 20 urodynamic testers at nine continence treatment centers. The protocol provides explicit and detailed guidelines for equipment, calibration, patient position, specific annotations, lay language bladder sensation parameters, visual leak point pressure techniques, modifications for prolapse, and data recording. A UDS Interpretation Guidelines document provides specific suggestions for validity and plausibility determination, expected ranges of urodynamic variables, and reasonable agreement of measuring systems. Both documents are available to urodynamic investigators on the Urinary Incontinence Treatment Network website (http://www.uitn.net/resourcesforphysicians.htm). CONCLUSIONS: Multicenter UDSs require a continuous quality improvement process and the development of UDS testing procedures and interpretation guidelines. PMID- 17270619 TI - Botulinum toxin B is not an effective treatment of refractory overactive bladder. AB - OBJECTIVES: To determine the efficacy and safety of botulinum toxin-B (BTX-B) in two groups of patients with urodynamically proven idiopathic detrusor overactivity (IDO) or neurogenic DO (NDO) refractory to conservative treatment. METHODS: This was a nonrandomized, prospective study. We diluted 5000 U of BTX-B in 20 mL of normal saline and injected it at 20 sites around the bladder, avoiding the trigone. The data collected at recruitment and 10 and 26 weeks postoperatively included number of incontinent episodes, frequency, and nocturia, King's Health Questionnaire score, and the urodynamic parameters of volume at the first overactive contraction and maximal cystometric capacity. RESULTS: A total of 25 patients were recruited, 20 with IDO and 5 with NDO. Only 7 patients, all with IDO, reported symptomatic improvement at the 10-week assessment. The symptoms had returned in these 7 patients at a median of 136 days (range 106 to 151) after injection. Of the remaining 20 patients, 16 (13 with IDO and 3 with NDO) thought an initial improvement had occurred but it had worn off or was wearing off by the first assessment. Two patients (both with NDO) reported no improvement. CONCLUSIONS: BTX-B had a limited duration of action, with most of its symptomatically beneficial effects wearing off by 10 weeks in most of our patients. The short duration of action for BTX-B suggests it is unlikely to gain widespread use in the treatment of DO. PMID- 17270620 TI - Long-term functional outcomes of ileal and sigmoid orthotopic neobladder procedures. AB - OBJECTIVES: To retrospectively compare the long-term functional outcomes of ileal and sigmoid orthotopic bladder replacements after radical cystectomy. METHODS: From 1990 to 2004, 123 male patients underwent orthotopic neobladder reconstruction after cystectomy; 75 underwent ileal neobladder (IN) and 48 sigmoid neobladder (SN) procedures. The observation period was 12.3 to 151.6 months (median 61.1). The voiding function of each patient was evaluated at three different observation periods: time 1, less than 5 years; time 2, 5 to 10 years; and time 3, more than 10 years after surgery. RESULTS: Almost every SN patient could void without assistance throughout the observation period. In contrast, the rate of spontaneous voiders was significantly low for the IN patients. Daytime continence was significantly worse in the SN than in the IN patients at time 2 (P <0.01), and the difference in nighttime continence between the two groups was even larger during the first 10 years after surgery (P <0.01). The postvoid residual urinary volume at time 2 was significantly larger in the IN than in the SN patients (P <0.01). No significant change in neobladder capacity was observed for either procedure throughout the observation period. The mean serum creatinine level was stable for both groups throughout the follow-up period. CONCLUSIONS: The IN and SN procedures result in different outcomes. The rate of spontaneous voiders was better in the SN group than in the IN group. The IN tends to provide better continence than the SN. In choosing a neobladder procedure, a proper understanding of the prospects of voiding functions is required. PMID- 17270621 TI - Long-term follow-up of patients with Stage T1 high-grade transitional cell carcinoma managed by Bacille Calmette-Guerin immunotherapy. AB - OBJECTIVES: To report the long-term outcome of patients with Stage T1 high-grade transitional cell carcinoma of the bladder treated initially by transurethral resection and adjuvant intravesical bacille Calmette-Guerin. METHODS: From June 1984 to November 1995, 78 consecutive patients with Stage T1 high-grade bladder cancer underwent transurethral resection and adjuvant intravesical bacille Calmette-Guerin therapy. The results at the interim follow-up (median 56 months) were reported in 1998. The median duration of follow-up for the present study was 107 months (range 16 to 238). The endpoints were tumor recurrence (Stage Ta, T1, or Tis), tumor progression (to T2 or greater), and disease-specific survival. RESULTS: Of the 78 patients, 34 (44%) were alive for the present analysis and 44 (56%) had died, 12 (16%) of transitional cell carcinoma and 32 (72%) of other causes. Recurrence was documented in 27 patients (35%) at a median of 8.5 months (range 5 to 129) after treatment, and progression in 14 patients (18%) at a median of 31.4 months (range 5 to 88) after treatment. The 2, 5, and 10-year recurrence-free survival and progression-free survival rates were 76%, 72%, and 62% and 92%, 82%, and 80%, respectively. The corresponding disease-free survival rates were 99%, 90%, and 85%. Disease progression occurred in 10 (37%) of 27 patients with recurrence, of whom 9 died. Of the 14 patients with disease progression, 12 died of their disease. CONCLUSIONS: Bacille Calmette-Guerin is an effective conservative treatment for patients with Stage T1 high-grade bladder cancer. More than one half the recurrences appeared within the first year, but a small risk remains throughout the patient's life. Progression during follow-up appears to carry a high risk of cancer-specific death. PMID- 17270622 TI - Reliability of frozen section examination of external iliac, hypogastric, and obturator lymph nodes during radical cystectomy: a multicenter study. AB - OBJECTIVES: To evaluate the accuracy of frozen section examination (FSE) for detecting lymph node (LN) metastasis in patients with bladder cancer undergoing radical cystectomy and pelvic LN dissection. To our knowledge, the accuracy of FSE to identify LN metastases in patients with bladder cancer is still undetermined. METHODS: The clinical data of 360 patients who had undergone radical cystectomy with pelvic lymphadenectomy for bladder cancer in six urologic institutions were retrospectively analyzed. The nodal regions included were the external iliac, hypogastric, and obturator LNs. The FSE results of the right and left LN regions were compared with the final histopathologic results of the respective LN regions. RESULTS: The final pathologic examination revealed nodal metastases in 65 patients (18.1%). Of the 720 right and left LN regions in 360 patients, 88 (12.2%) were metastatic at the final pathologic examination. Although the FSE findings were negative, the final pathologic examination revealed LN metastases in 26 patients and in 29 pelvic LN regions. All LN regions with positive FSE findings were positive at the final pathologic examination. When we considered the 720 LN regions, the sensitivity, specificity, and positive and negative predictive values for FSE were 67%, 100%, 100%, and 95.6%, respectively. CONCLUSIONS: Until innovations in imaging methods improve nodal staging in patients with bladder cancer, performing FSE of the external iliac, hypogastric, and obturator LNs seems to be a reliable procedure for the evaluation of the LNs. The information obtained with FSE of the LNs can be used to determine intraoperatively the extent of LN dissection. PMID- 17270623 TI - Urodynamic evaluation of urethral competency in women with posterior vaginal support defects. AB - OBJECTIVES: To determine whether posterior vaginal wall support defects mask stress incontinence and the effects of these defects on common urodynamic tests used to evaluate urethral competency. METHODS: We performed a prospective analysis of urodynamic evaluation with and without posterior vaginal stabilization in 54 women with Stage 2 or greater posterior vaginal prolapse and 54 women with Stage 0 and 1 posterior vaginal prolapse. RESULTS: Posterior vaginal stabilization resulted in statistically significant reductions in the Valsalva leak point pressure, maximal urethral closure pressure, and pressure transmission ratios in the case group and inconsistent changes in the control group. Posterior vaginal stabilization unmasked stress incontinence in 12 (54%) of 22 case patients but none of the control patients. Previous incontinence surgery (odds ratio 57.4, 95% confidence interval 5.8 to 568, P = 0.001) was the strongest predictor for occult stress incontinence in patients with Stage 2 or greater rectocele. Also, notable, but less significant, associations were found between hysterectomy (odds ratio 6.7, 95% confidence interval 1.5 to 29, P = 0.01) and severity of rectocele (odds ratio 1.9, 95% confidence interval 1.1 to 3.3, P = 0.02) with occult incontinence. CONCLUSIONS: The results of our study have shown that stress incontinence can be masked in women with Stage 2 or greater posterior vaginal support defects. PMID- 17270624 TI - Five-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study. AB - OBJECTIVES: To compare the efficacy and safety of transurethral microwave thermotherapy (TUMT) with ProstaLund Feedback Treatment, using the CoreTherm device, with transurethral resection of the prostate (TURP) 5 years after treatment. METHODS: This prospective, randomized, multicenter study was conducted at 10 centers in the United States and Scandinavia. A total of 154 patients with benign prostatic hyperplasia were randomized to TUMT or TURP in a 2:1 ratio. Patients were followed up at 3, 6, 12, 24, 36, 48, and 60 months after treatment. The intermediate results at 12 and 36 months have been previously reported. The treatment outcome at 5 years was evaluated with the International Prostate Symptom Score (IPSS), quality of life question (QOL), peak urinary flow rate (Qmax), postvoid residual urine volume, and prostate volume. The CoreTherm device differs from other microwave devices in that the intraprostatic temperature is constantly measured during the procedure to guide the treatment. RESULTS: Of the 154 patients, 66% completed the 60 months of follow-up. Statistically significant improvements in the TUMT and TURP groups were observed for IPSS, QOL, and Qmax at 60 months. The average values for the TUMT group were an IPSS of 7.4, QOL score of 1.1, and Qmax of 11.4 mL/s. The values for the TURP group were IPSS of 6.0, QOL score of 1.1, and Qmax of 13.6 mL/s. No statistically significant differences were found in any of these variables between the two treatment groups. In the TUMT group, 10% needed additional treatment versus 4.3% in the TURP group. CONCLUSIONS: The clinical outcome 5 years after TUMT using the CoreTherm device was comparable to the results seen after TURP. The safety of TUMT using the CoreTherm device compared favorably with that of TURP. PMID- 17270627 TI - Cutoff value of urinary arginine vasopressin for nocturnal polyuria in elderly men. AB - OBJECTIVES: To determine the cutoff value of early-morning urinary arginine vasopressin (uAVP)/urinary creatinine (uCr) for patients with nocturnal polyuria (NP), and to investigate whether abnormal secretion of AVP at nighttime is a risk factor of NP in elderly men. METHODS: A total of 189 men older than 50 years of age with nocturia were enrolled. The frequency volume chart was recorded. The uAVP, urinary sodium, uCr, and osmolarity of a single urine sample voided at 6:00 am were measured in all cases. Two definitions of NP--nocturnal urine volume/24 hr production greater than 0.35 (NP index [NPI] definition) and a nocturnal urine volume of 0.9 mL/min x the sleeping duration or greater (NUV definition)--were used for analysis. RESULTS: uAVP/uCr was an independent predictor for NP according to the NPI and NUV definitions. The cutoff value of uAVP/uCr for NP was 23.4 pg/mL/Cr according to the NPI definition and 28.3 pg/mL/Cr according to the NUV definition. The sensitivity of the cutoff value according to the NPI and NUV definitions was 69% and 77%, respectively, and the specificity was 61% and 66%, respectively. In both NP definitions, 31% and 38% of the patients with a uAVP/uCr greater than the cutoff value showed NP. Significant differences in NUV and urine osmolarity, but not in uAVP/uCr and uNa/uCr, between the NP group and the non-NP group were found using both NP definitions. CONCLUSIONS: We demonstrated that age and uAVP/uCr were independent predictive factors for nocturia in patients with NP. The cutoff value of uAVP/uCr is a useful screening marker for NP in elderly men with nocturia. PMID- 17270628 TI - Prostate volume is strongest predictor of cancer diagnosis at transrectal ultrasound-guided prostate biopsy with prostate-specific antigen values between 2.0 and 9.0 ng/mL. AB - OBJECTIVES: Data have suggested benign prostatic hyperplasia, and not cancer, as the major reason for elevated prostate-specific antigen (PSA) values between 2.0 and 9.0 ng/mL. If this hypothesis were correct, within these ranges, a smaller prostate volume would be a stronger predictor of cancer than the PSA level itself (the relative contribution from cancer is greater in smaller glands). METHODS: We examined our institutional data set of transrectal ultrasound-guided procedures from 2000 to 2003. We studied patients who presented for their first prostate biopsy with a PSA level of 2.0 to 9.0 ng/mL. The indications for biopsy were elevated age-specific PSA level or abnormal digital rectal examination findings. Other covariates included patient age, abnormal transrectal ultrasound findings, transrectal ultrasound volume, and biopsy sampling scheme. Univariate analyses were used to assess the association between each variable and cancer diagnosis. Multivariate logistic regression modeling was then used to determine the adjusted risk factors for cancer at biopsy. RESULTS: On univariate analyses, all measured covariates were predictive of cancer. On multivariate modeling, the significant risk factors (in order of strength) for positive biopsy findings were smaller prostate volume (odds ratio [OR] 0.26, P <0.001), increasing age (OR 1.72, P <0.001), increasing PSA (OR 1.64, P <0.001), and the presence of hypoechoic lesions (OR 2.42, P <0.001). CONCLUSIONS: When the PSA level is in the 2.0 to 9.0 ng/mL range, a smaller prostate volume is the strongest predictor of cancer detection. These data support previous studies suggesting the amount of benign prostatic hyperplasia, and not cancer, as the major factor responsible for elevated PSA. PMID- 17270629 TI - Use of prostate-specific antigen velocity to follow up patients with isolated high-grade prostatic intraepithelial neoplasia on prostate biopsy. AB - OBJECTIVES: No consensus has been reached about the optimal follow-up for patients with an isolated finding of high-grade prostatic intraepithelial neoplasia (HG-PIN) on prostate biopsy. Early studies reported that approximately one half of men with HG-PIN were diagnosed with prostate cancer (CaP) within a few years. However, more recent studies, using extended biopsy protocols, have shown that HG-PIN may be less predictive of CaP on repeat biopsy in the short term. Thus, our objective was to identify the clinical factors that could help predict which men with isolated HG-PIN were at the greatest risk of subsequent CaP detection. METHODS: In 190 men from a CaP screening study with an initial biopsy finding of HG-PIN, we compared the prostate-specific antigen velocity (PSAV) between patients who were later diagnosed with CaP and those who were not. Multivariate models were constructed for the ability to predict CaP detection. RESULTS: The median PSAV was significantly greater in the men with HG-PIN who were subsequently diagnosed with CaP (P = 0.03). A PSAV threshold of 0.75 ng/mL/yr predicted which men with HG-PIN would ultimately be diagnosed with CaP (P = 0.007). On multivariate analysis, including PSAV, age, and initial PSA level, PSAV was the only significant predictor of subsequent CaP detection. CONCLUSIONS: Among the men with an isolated finding of HG-PIN on prostate needle biopsy, PSAV helps to identify those men who are subsequently diagnosed with CaP. Thus, we advocate the use of the PSAV to help guide the need for repeat biopsy in men with HG-PIN. PMID- 17270630 TI - Interleukin 6 is associated with cachexia in patients with prostate cancer. AB - OBJECTIVES: To evaluate the relationship between serum interleukin (IL)-6 and cachexia in patients with prostate cancer. METHODS: Serum levels of IL-6, total protein, albumin, total cholesterol, and hemoglobin concentration were determined in 164 blood samples from patients with prostate cancer. The body mass index and performance status were also determined. RESULTS: The serum total protein, albumin, and cholesterol levels, hemoglobin levels, and body mass index of the patients whose serum IL-6 level was 7 pg/mL or greater were significantly lower (P <0.05) than the corresponding values in patients with a serum IL-6 level of less than 7 pg/mL. The serum IL-6 level of patients with a serum albumin level of less than 3.5 g/dL, serum total protein level of less than 7.0 g/dL, serum total cholesterol level of less than 180 mg/dL, hemoglobin level of less than 11.0 g/dL, and body mass index of less than 21 kg/m2 were significantly greater (P <0.05) than the values in their respective counterparts. A significant correlation was found between the elevation of serum IL-6 and performance status (P <0.05). The mortality rate of patients with greater serum IL-6 levels was significantly greater than that of those with lower serum IL-6 levels in patients with untreated disease, patients in remission, and patients with relapse (all P <0.05). CONCLUSIONS: These findings suggest that IL-6 may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer (all P <0.05). PMID- 17270631 TI - Contemporary laparoscopic and open radical retropubic prostatectomy: pathologic outcomes and Kattan postoperative nomograms are equivalent. AB - OBJECTIVES: Although contemporary cohort comparisons are lacking, open surgeons have questioned the oncologic efficacy of laparoscopic radical prostatectomy (LRP) owing to the lack of haptic feedback. As such, we compared the pathologic outcomes and predicted the progression-free survival after open radical prostatectomy (ORP) and LRP in a single referral setting within a defined period, thereby isolating the effect of the surgical technique alone. METHODS: Data were collected on 169 ORPs and 111 LRPs performed at our institution from May 2003 to May 2005. The surgical pathologic outcomes were compared, and the Kattan postoperative nomogram was used to calculate the 5 and 7-year progression-free probabilities after ORP and LRP. RESULTS: On univariate analysis, no differences were found in age, Gleason sum, stage, margin status, extracapsular extension, and seminal vesicle invasion. The positive margin rate was 29% for LRP and 35% for ORP (P = 0.29), and no difference was found even after stratifying by pathologic stage. After controlling for Gleason sum, extracapsular extension, seminal vesicle invasion, nodal involvement, margin status, and preoperative prostate-specific antigen, no difference was found in detectable prostate specific antigen after ORP and LRP (P = 0.73). When the Kattan postoperative nomogram was used to compute the biochemical progression-free probabilities, no differences were found at 5 (P = 0.51) and 7 years (P = 0.50). CONCLUSIONS: In this contemporary series without the confounding effects of stage migration, regional practice variation, or the use of historical controls, the pathologic outcome after conventional LRP was similar to that after ORP. Biochemical progression-free survival was also similar using a validated multivariate predictive model. PMID- 17270632 TI - Fertility issues for men with newly diagnosed prostate cancer. AB - OBJECTIVES: With the increased use of prostate-specific antigen screening, younger men are being diagnosed with prostate cancer. A subset of these men is still interested in potentially having children after cancer treatment. To our knowledge, the topic of future fertility in patients with newly diagnosed prostate cancer has not previously been reported. METHODS: The charts of 8 patients with prostate cancer who were interested in future fertility before treatment were retrospectively reviewed. Preceding definitive treatment, the men underwent fertility counseling and were counseled to preserve semen before treatment. RESULTS: All 8 patients decided to have their semen stored using cryopreservation before their operation. After undergoing radical prostatectomy, one of the patients and his wife underwent successful intrauterine insemination and bore a child. CONCLUSIONS: A subset of men, regardless of age, diagnosed with prostate cancer will be interested in preserving their fertility for the future. Fertility options and potential counseling should be part of the routine pretreatment appointments in men undergoing treatment of prostate cancer. PMID- 17270633 TI - Artificial urinary sphincter placement in elderly men. AB - OBJECTIVES: To evaluate the outcomes of primary artificial urinary sphincter (AUS) placement for the treatment of postprostatectomy stress urinary incontinence in patients aged 75 years or older at surgery. METHODS: From September 1987 through June 2005, 33 men aged 75 years or older underwent AUS insertion for postprostatectomy stress urinary incontinence. Through retrospective chart review and personal/family interview, the patients' outcomes with regard to continence, complications, and the need to deactivate the AUS for medical or social reasons were determined. RESULTS: Four patients were lost to follow-up and were excluded from the analysis. The mean patient age was 77.6 years (range 75 to 83). The average follow-up was 5.0 years (range 1 to 11). After AUS insertion, the mean pad use improved from 6.7 (range 3 to 10) to 0.8 (range 0 to 2) per day. Overall, 16 (55%) of 29 men reported no complications. AUS revision was necessary in 4 men (14%), and sphincter removal in 4 (14%). Six men (21%) required deactivation of the implant because of poor overall health an average of 47 months after placement. The "success" rate improved to 72% (21 of 29 men) when cuff deactivation without revision or removal was not considered a complication. CONCLUSIONS: In our study, elderly men did well after AUS placement for postprostatectomy stress urinary incontinence. The procedure should not be withheld solely on the basis of the age of the patient. PMID- 17270634 TI - Prostate-specific antigen kinetics after brachytherapy or external beam radiotherapy and neoadjuvant hormonal therapy. AB - OBJECTIVES: To characterize the kinetics of prostate-specific antigen (PSA) after radiotherapy (RT) and neoadjuvant hormonal therapy (NHT) for localized prostate cancer. METHODS: The PSA kinetics of 75 consecutive patients who had undergone RT and NHT (median time 4 months) were followed up for a minimum of 24 months after treatment. RT included a permanent iodine-125 implant (n = 29), a temporary iridium-192 implant as a boost to external beam RT (n = 21), and sole external beam RT (n = 25). A median number of 11 PSA levels per patient were analyzed. RESULTS: After a first nadir (median level 0.1 ng/mL 3 months after RT), rising PSA levels were found in 83% of patients and progressively rising PSA levels until the end of follow-up or salvage hormonal therapy for 21% of patients. The PSA levels dropped again after one (23%), two (21%), or more (17%) consecutive increases up to a median level of 0.6 ng/mL (median time 16 months after RT), so that a nadir of 0.1 ng/mL was reached for a second time (median time 35 months after RT). A first nadir of less than 0.1 ng/mL, a PSA increase of less than 1 ng/mL, and a longer PSA doubling time (median time 10 months) were strongly predictive for long-term biochemical control. CONCLUSIONS: Temporarily rising PSA levels can be expected for most patients after primary RT and NHT following a first nadir. The increasing effects of testosterone owing to NHT withdrawal have a stronger effect than RT in the first months after treatment. PMID- 17270635 TI - Large-scale study of clinical impact of PSA velocity: long-term PSA kinetics as method of differentiating men with from those without prostate cancer. AB - OBJECTIVES: To assess the longitudinal prostate-specific antigen (PSA) changes in a screening population with or without prostate cancer during a 10-year period. METHODS: Serial PSA measurements performed during a 10-year period were evaluated in 4272 participants of a screening program who had no evidence of prostate malignancy and 528 men who eventually developed prostate cancer. RESULTS: Of the 4272 men with no evidence of prostate cancer, the mean total PSA level increased from 1.16 to 1.49 ng/mL during the 10 years, corresponding to a PSA velocity (PSAV) of 0.03 ng/mL/yr. Younger men had lower total PSA values throughout the 10 year period. Of the 528 patients with prostate cancer, the total PSA level increased from 2.19 at 10 years before diagnosis to 6.09 ng/mL at the time of positive biopsy findings, corresponding to a PSAV of 0.39 ng/mL/yr. The PSAV increased in the years before diagnosis (0.225 ng/mL/yr in the 8 to 10 years before diagnosis compared with 0.98 ng/mL/yr in the 2 years before diagnosis). The PSAV was greater in patients with Stage pT3-T4 cancer than in men with organ confined tumors (median 0.53 versus 0.32 ng/mL/yr; P <0.001). CONCLUSIONS: In men with prostate cancer, the PSAV was significantly greater than in those without prostate cancer and correlated with pathologic stage and Gleason score but not with prostate volume. In the patients with prostate cancer, the PSAV increased in the years before the diagnosis. In contrast, men without prostate cancer had only slight PSA changes over time. Hence, PSA kinetics may help identify men with potentially curable prostate cancer. PMID- 17270636 TI - Modified perianal/pericapsular anesthesia for transrectal biopsy of prostate in patients with anal rectal problems. AB - OBJECTIVES: To modify our technique of perianal anesthesia and use it in patients with painful conditions of the rectum and/or anus. METHODS: A total of 31 consecutive patients with anal-rectal problems underwent prostate needle biopsy. Of these, 17 were referred to our hospital after vain attempts to insert a transrectal ultrasound probe. Patients received a perianal-pericapsular injection of 1% lidocaine. Pain perception was separately assessed for probe insertion and biopsies using a visual pain analog score. RESULTS: Only in 1 patient were we unable to insert the transrectal ultrasound probe. The mean patient age was 65.28 +/- 5.35 years. We performed a mean of 12.25 biopsies per case. At probe insertion, the mean pain score was 2.2 +/- 0.83. During the biopsy punctures, the mean pain level was 2.53 +/- 1.054. We did not find any increase in the complication rate related to the anesthesia method. CONCLUSIONS: Modified perianal anesthesia can be used for transrectal ultrasound-guided biopsy of the prostate in patients with anal-rectal problems, because it provides significant pain relief. PMID- 17270637 TI - Weekly docetaxel and epirubicin in treatment of advanced hormone-refractory prostate cancer. AB - OBJECTIVES: To evaluate the efficacy and safety of a new regimen that combines weekly docetaxel and weekly epirubicin for the treatment of advanced hormone refractory prostate cancer. METHODS: Docetaxel 30 mg/m2 and epirubicin 30 mg/m2 were intravenously administered on a weekly basis, for a maximum of 24 cycles. The therapy was discontinued after the first 12 cycles in the patients who responded or had stable disease and was resumed as soon as any signs of progression were noted. RESULTS: Of the 38 evaluable patients, 26 achieved a confirmed greater than 50% decrease in prostate-specific antigen level (68.4%, 95% confidence interval [CI] 51.2% to 82.0%). The median response duration was 8.8 months (95% CI 6.2 to 11.8), and the median time to progression was 7.4 months (95% CI 5.6 to 9.6). Pain was rapidly reduced in 24 (72.7%, 95% CI 54.2 to 86.7) of the 33 patients who were symptomatic at baseline. Of the 38 patients, 21 resumed therapy after the planned interruption; of these, 3 had a prostate specific antigen response (14.2%) and 12 had stable disease (57.1%). The regimen was well tolerated. Grade 3 neutropenia occurred in 15.7% of the patients, grade 3 anemia in 13.1%, and grade 3 thrombocytopenia in 7.8%. CONCLUSIONS: The results of this study have suggested the feasibility and tolerability of the combination of weekly docetaxel and weekly epirubicin, which led to a rapid and long-lasting decrease in prostate-specific antigen levels and a palliative response in patients with advanced hormone-refractory prostate cancer. PMID- 17270638 TI - Critical assessment of ideal nodal yield at pelvic lymphadenectomy to accurately diagnose prostate cancer nodal metastasis in patients undergoing radical retropubic prostatectomy. AB - OBJECTIVES: To study the relation between the number of removed and examined lymph nodes at pelvic lymph node dissection and the rate of lymph node invasion (LNI). METHODS: A total of 858 patients aged 45 to 85 years were predominantly treated with extended pelvic lymph node dissection before radical retropubic prostatectomy. The pretreatment prostate-specific antigen level was 0.24 to 49.9 ng/mL (median 5.8). Most lesions were Stage T1c (55.2%) or T2 (40.7%), with a biopsy Gleason sum of 6 or less (62.2%) or 7 (25.1%). Receiver operating characteristic curve coordinates were used to determine the probability of finding LNI according to the number of removed and examined lymph nodes. Moreover, the association between the number of removed lymph nodes and LNI was tested in univariate and multivariate logistic regression models. RESULTS: From 2 to 40 nodes (mean 15, median 14) were removed and examined, and 88 patients (10.3%) had LNI. The LNI rate increased with the number of removed nodes (P <0.001): 2 to 10 nodes removed, 5.6% LNI rate; 10 to 14 nodes removed, 8.6% LNI rate; 15 to 19 removed, 10.2% LNI rate; and 20 to 40 removed, 17.6% LNI rate. On multivariate analysis, the number of examined nodes predicted for LNI (P <0.001), after accounting for prostate-specific antigen level, clinical stage, and biopsy Gleason sum. The receiver operating characteristic coordinate plot indicated that the removal of 28 nodes yielded a 90% ability to detect LNI. Conversely, the assessment of 10 or fewer nodes was associated with a virtually zero probability of finding LNI. CONCLUSIONS: We have provided a critical assessment of the concept that the nodal yield at pelvic lymph node dissection is closely associated with the rate of LNI. PMID- 17270639 TI - Testicular volume measurement: comparison of ultrasonography, orchidometry, and water displacement. AB - OBJECTIVES: To determine the accuracy of orchidometry and ultrasonography for measuring the testicular volume by comparing the resultant measurements with the actual testicular volume in humans. METHODS: The testicular volume of 40 testes from 20 patients with prostate cancer (mean age +/- SD 74.5 +/- 7.5 years) was measured using the Prader orchidometer and ultrasonography before therapeutic bilateral orchiectomy. The ultrasound measurements of testicular volume were calculated using three formulas: length (L) x width (W) x height (H) x 0.52, L x W2 x 0.52, and L x W x H x 0.71. The actual testicular volumes were determined by water displacement of the surgical specimen. RESULTS: The mean actual testicular volume of the 40 testes was 9.3 cm3 (range 2.5 to 23.0). A strong correlation was found between the testicular volume calculated by the three ultrasound formulas and the actual volume (r = 0.910 to 0.965, P <0.0001) and was stronger than the correlation with the Prader orchidometer (r = 0.818, P <0.0001). The smallest mean difference from the actual testicular volume was observed with the formula L x W x H x 0.71, which overestimated the actual volume by 0.80 cm3 (7.42%). The measurements using the Prader orchidometer correlated with the actual testicular volume and with the testicular volume calculated using the three ultrasound formulas (r = 0.801 to 0.816, P <0.0001). However, the orchidometer measurements had the largest mean difference from the actual testicular volume (6.68 cm3, 81.7%). CONCLUSIONS: The results of this study have shown that measuring the testicular volume by ultrasonography is more accurate than by the Prader orchidometer, and the formula L x W x H x 0.71 was the most accurate for calculating the testicular volume. PMID- 17270640 TI - Testicular volume measurements using Prader orchidometer versus ultrasonography in patients with infertility. AB - OBJECTIVES: To compare the accuracy of testicular volume measurements with the Prader orchidometer versus ultrasonography. METHODS: The volume of 938 testes in 469 men with infertility (mean age 35.8 years) was measured using a Prader orchidometer and by ultrasonography. The ultrasound testicular volumes were calculated using the formula length x width x height x 0.71. To compare any differences between the methods according to testicular size, the patients were divided into six groups according to the ultrasound-determined volume: less than 5, 5 to 10, 10 to 15, 15 to 20, 20 to 25, and 25 cm3 or more. RESULTS: The mean volume by orchidometry and ultrasonography was 18.7 and 13.7 cm3 for the right testis and 18.0 and 12.5 cm3 for the left, respectively, and was significantly overestimated by orchidometry (P <0.0001; by 5.1 cm3 on the right and 5.5 cm3 on the left). The largest differences between methods were observed for volumes of 10 to 15 cm3 on the right and 5 to 10 cm3 on the left. The difference between the methods decreased as the ultrasound-determined volume increased (r = 0.636 on the right; r = 0.598 on the left testis). Nonetheless, the Prader orchidometric measurements showed a strong correlation with the ultrasound measurements (r = 0.707 on the right; r = 0.746 on the left). CONCLUSIONS: The testicular volume estimated by Prader orchidometry correlated closely with the measurements by ultrasonography. However, the orchidometer overestimated the testicular volume, especially in small testes. PMID- 17270641 TI - Immediate improvement in penile hemodynamics after cessation of smoking: previous results. AB - OBJECTIVES: To assess the chronologic relationship between the cessation of smoking and the restoration of erectile function. Smoking is associated with an increased risk of erectile dysfunction. METHODS: Twenty active smokers (20 to 40 cigarettes/day) affected by erectile dysfunction (International Index of Erectile Function 5-item score less than 21) were enrolled in the study. The mean age was 40 years. All the patients underwent penile color Doppler ultrasonography during the basic and dynamic phases (10 microg prostaglandin E1). A second Doppler evaluation was performed 24 to 36 hours after cessation of smoking. The peak systolic velocity (PSV) and end-diastolic velocity (EDV) were recorded. The PSV and EDV cutoff value was 30 cm/s and 5 cm/s, respectively. RESULTS: Of the 20 patients, 10 (50%) had normal PSV values but only 5 (25%) had normal EDV values at the baseline Doppler evaluation. All the patients (100%) had normal PSV values at the second penile Doppler evaluation after smoking withdrawal, and 17 (85%) also had normal EDV values. The average PSV was 40.1 and 50.3 cm/s (P = 0.09) and the mean EDV was 6.8 and 2.4 cm/s (P <0.01) at the baseline penile Doppler examination and after smoking withdrawal, respectively. CONCLUSIONS: Within 24 to 36 hours of the cessation of cigarette smoking, the color Doppler parameters demonstrated a significant improvement in EDV and a trend toward an increase in PSV. Additional clinical evaluation is required to further characterize the expeditious improvement in erectile function after the cessation of smoking. PMID- 17270642 TI - Gross hematuria in children: a ten-year review. AB - OBJECTIVES: Gross hematuria in children is uncommon. We reviewed our experience characterizing its clinical presentation and diagnosis. METHODS: The charts of all patients who presented for the 10-year period of 1994 through 2003 were reviewed, and 342 patients were identified. Of these 342 patients, 272 were boys (80%) and 70 (20%) were girls. At presentation, 21 patients (6%) were younger than 3 years (17 were boys and 4 were girls); 199 (58%) were 3 to 12 years old (155 were boys and 44 were girls); and 122 (36%) were 13 to 20 years old (100 were boys and 22 were girls). RESULTS: Of the 272 male patients, 52 (19%) had benign urethrorrhagia; 48 (14%) had trauma; and 48 had a urinary tract infection (14%), and 10 of those also had urologic anomalies. Of the 342 patients, 45 (13%) had one or more congenital urologic anomalies. Of these 45 patients, 20 boys and 2 girls had vesicoureteral reflux, 10 boys had posterior urethral valves, 7 boys and 1 girl had ureteropelvic junction obstruction, 7 boys had proximal hypospadias, 2 boys and 1 girl had ureterovesical junction obstruction, 2 boys and 1 girl had ureterocele, and 1 boy had caliceal diverticulum. Also, 18 patients (5%) had stones; 3 had low-grade bladder transitional cell carcinoma; and 1 had a Wilms tumor. For 118 patients (34%; 95 boys and 23 girls), no etiology was found. CONCLUSIONS: Gross hematuria most often had a benign cause in children and adolescents. It was more common in boys for almost all etiologic categories and ages. The extent of the urologic evaluation should depend on the clinical setting. Voiding cystourethrography is useful in those with suspicious ultrasound findings, urinary tract infection, or voiding symptoms. Cystoscopy should be reserved for the minority in whom hematuria persists or those with ambiguous imaging study findings. PMID- 17270643 TI - Expanding use of ureteral access sheath for stones larger than access sheath's internal diameter. AB - The internal diameter of the ureteral access sheath limits the size of stones that can be removed during flexible ureteroscopy. We describe a technique that allows removal of larger stones, which are entrapped and removed en bloc with the access sheath. This new technique was shown to be efficient and safe. PMID- 17270644 TI - Technique for pure transverse colon continent cutaneous urinary diversion. AB - We describe a new method for constructing a pure transverse colon reservoir with two short segments of transverse colon fashioned as Monti tubes that are placed in a serous-lined extramural tunnel for construction of the efferent segment and for ureteral reimplantation, respectively. PMID- 17270645 TI - Technical modifications to laparoscopic Boari flap. AB - INTRODUCTION: To describe technical modifications to the laparoscopic Boari flap ureteroneocystostomy procedure. TECHNICAL CONSIDERATIONS: Removal of ureteral stents with conversion to percutaneous nephrostomy drainage before surgery allowed for optimization of tissue quality and visualization during operative repair. Adherence to specific dimensional ratios during flap excision consistently provided for adequate tissue for successful Boari flap construction. A mucosal modification to the Boari flap allowed for an increase in the circumference of the anastomosis and provided an additional means to fortify the suture line and promote healing. Raised mucosal flaps on the Boari flap facilitated construction of a nonrefluxing anastomosis. Finally, a 2-mm needlescopic port placed at the level of the anastomosis facilitated simplified intracorporeal double-J ureteral placement. CONCLUSIONS: Laparoscopic Boari flap ureteroneocystostomy is an effective treatment of distal ureteral stricture disease. The technical modifications describe in this report aim to contribute to increased success rates in patients who undergo this procedure. PMID- 17270646 TI - Complete penoscrotal transposition. PMID- 17270647 TI - "RuZhu": a bead-like penile implant. PMID- 17270648 TI - Peritonitis carcinomatosa in a patient with recurrent "superficial" bladder cancer treated with cystectomy and nephroureterectomy. AB - We report on a 45-year-old woman treated with cystectomy after failure of bacille Calmette-Guerin therapy for superficial transitional cell carcinoma. After 9 months, left-sided nephroureterectomy was performed for recurrence in the left ureter. The pathologic examination revealed carcinoma in situ and no tumor positive lymph nodes (pTisN0Mx). At 2.5 years later, she complained of abdominal distension and pain. She underwent bilateral removal of the ovaries, infracolic omentectomy, and liver biopsy because of suspicious lesions on the liver. Pathologic examination revealed extensive peritoneal spread of transitional cell carcinoma. The seeding potential of high-grade urothelial cancer is well known; however, we found no clear explanation for the peritoneal spread of tumor cells in this patient that occurred years after the surgical procedures. PMID- 17270649 TI - Urothelial carcinoma recurrence in ileal orthotopic neobladder: urethrectomy and creation of ileal conduit. AB - A patient who had previously undergone radical cystoprostatectomy and ileal neobladder with the Studer technique presented with a recurrence of urothelial carcinoma in the neobladder and urethra. Surgical treatment consisted of resection of the neobladder, urethrectomy, and creation of an ileal conduit using a separately isolated segment of ileum. Pathologic analysis revealed high-grade urothelial carcinoma implants to the Studer pouch and urethra, with spread to the mesenteric lymph nodes draining the pouch. Intraluminal tumor cell seeding appears to be an important mechanism of metachronous transitional cell carcinoma recurrence in the urethra and ileal mucosa of a neobladder. PMID- 17270650 TI - Primary extrarenal nephroblastomatosis. AB - We report an unusual case of primary extrarenal nephroblastomatosis present along the tunica albuginea of a testis found incidentally during routine inguinal orchiopexy. The worldwide published data and embryologic implications of extrarenal nephroblastomatosis and Wilms tumor are discussed. PMID- 17270651 TI - Synchronous advanced scrotal verrucous carcinoma with peripheral T-cell lymphoma. AB - Scrotal verrucous carcinoma is extremely rare. Classic cases have been suggested to be occupation related. We report on a 65-year-old male drifter, who had concomitant multiple condyloma acuminatum and advanced verrucous carcinoma of the right hemiscrotal skin with peripheral T-cell lymphoma and extensive lymphadenopathy. To our knowledge, it is the first case of synchronous verrucous carcinoma and peripheral T-cell lymphoma. The patient died of disseminated disease 2 months after undergoing wide excision of the tumor. A brief discussion of the diagnosis, treatment, and prognosis is presented. PMID- 17270652 TI - Humoral hypercalcemia of penile carcinoma. AB - Hypercalcemia is a common life-threatening complication associated with several genitourinary malignancies. Parathyroid-related peptide has been shown to cause hypercalcemia in several solid tumors but rarely in penile cancer. We report a case of advanced penile cancer with hypercalcemia and associated dysphagia. Treatment is clinically challenging and should be definitive as soon as the patient has been stabilized. Serum calcium measurement can be used for monitoring the outcome and follow-up in such patients. Dysphagia is a rare but potential symptom of hypercalcemia, but additional studies are needed to prove this association. PMID- 17270653 TI - Primary retroperitoneal teratoma presenting as an adrenal tumor in an adult. AB - Primary teratomas in the retroperitoneum are rare in adults. Most teratomas in this region are secondary to germ cell tumors of the testes or ovaries. We describe a case of mature cystic teratoma that was clinically suggestive of an adrenal myelolipoma. Resection was attempted using laparoscopy but was converted to open adrenalectomy to ensure complete resection. Because of the risk of malignancy, follow-up radiographic studies were performed to ensure the oncologic efficacy of resection. The patient has been free of recurrence for longer than 18 months. PMID- 17270654 TI - Subcutaneous metallic mercury injection for penile augmentation. AB - Mercury intoxication is rare. Most often it is associated with occupational exposure or suicide attempts. We present the case of a 72-year-old patient who received a subcutaneous injection of metallic mercury into his penis for the purpose of penile aesthetic augmentation. Total phallectomy and perineal urethrostomy was performed, followed by chelation therapy. To our knowledge, this is the first report of penile subcutaneous mercury injection for aesthetic augmentation. PMID- 17270655 TI - Antidepressant-associated changes in semen parameters. AB - We describe 2 cases of patients referred for evaluation of male infertility who had antidepressant medication-associated changes in sperm motility and/or concentration. The physical examination and endocrinologic study findings were unremarkable in each case. Analysis of the initial semen specimens revealed oligospermia, impaired motility, and abnormal morphology in each patient while they were taking serotonin reuptake inhibitors. Repeat semen analyses performed 1 to 2 months after discontinuation of the antidepressants demonstrated marked improvements in sperm concentration and motility. Additional assessment of the potential impact of antidepressant medications on male fertility is warranted. PMID- 17270656 TI - New unstable bladder model in hypercholesterolemia rats. AB - OBJECTIVES: To evaluate the voiding function of the new vasculogenic erectile dysfunction (ED) model in hypercholesterolemic rats. METHODS: We used 14 adult 12 week-old male Sprague-Dawley rats. The cholesterol group received a 1% cholesterol diet for 8 weeks. During the initial 2 weeks, they also drank water containing 3 mg/mL of NG-nitro-L-arginine methyl ester. After 8 weeks, we performed cystometrography, a detrusor strip contraction study, and pathologic examination of the detrusor to confirm voiding dysfunction. The results of the cholesterol and control groups were compared. RESULTS: Compared with the control group values, the mean serum cholesterol and body weight were significantly elevated in the cholesterol group. The cholesterol group had shorter voiding intervals (377.6 +/- 205.4 versus 121.8 +/- 79.6 seconds, P <0.01) and a smaller functional bladder volume (1.4 +/- 0.7 versus 0.7 +/- 0.3 mL, P <0.05) on cystometrography compared with the control group. In the detrusor strip study, the cholesterol group had greater tension in spontaneous activities and an increase (13.1% +/- 5.6% versus 28.4% +/- 16.2%, P <0.05) in the proportion of purinergic components. CONCLUSIONS: This vasculogenic ED rat model showed significantly frequent voiding on cystometrography. Considering the many epidemiologic and experimental data, in addition to the data from this model, ED and overactive bladder could share similar pathophysiologic features or be two symptoms of a systemic disorder. This rat model should be useful in evaluating the mechanism of ED and overactive bladder. PMID- 17270657 TI - Effect of obese and lean Zucker rat sera on human and rat prostate cancer cells: implications in obesity-related prostate tumor biology. AB - OBJECTIVES: Several reports have demonstrated the effects of obesity on prostate cancer. Also several reports have linked expression of vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (FGF-2) to prostate cancer aggressiveness. The objective of this study was to determine whether a difference exists between lean and obese Zucker rat sera on proliferation prostate cancer cell lines, as well as to examine the differences in FGF-2 and VEGF concentrations. METHODS: Ten-week-old female obese and lean Zucker rat sera were subjected to charcoal stripping and tested for the proliferation of human LNCaP and rat AT3B-1 prostate cancer cells. An acetonitrile extract of the charcoal used to strip the sera was also tested for mitogenicity. VEGF and FGF-2 concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: Both unstripped and charcoal-stripped obese rat sera had a greater mitogenic effect than did the lean sera on the LNCaP cell line. Charcoal stripping of both obese and lean sera reduced the mitogenic effect on the AT3B-1 cell line. The acetonitrile extract of the charcoal used to strip the sera was unable to recover this proliferative effect. The concentration of VEGF was greater in the obese serum than in the lean serum, and charcoal stripping reduced the concentrations of both FGF-2 and VEGF. CONCLUSIONS: The finding of greater VEGF in obese rat sera, as well as greater mitogenic responses on human prostate cancer cells in vitro, suggests this as one of the many possible mechanisms involved in obesity related prostate cancer biology. PMID- 17270658 TI - Evaluation of AIbZIP and Cdc47 as markers for human prostatic diseases. AB - OBJECTIVES: Benign prostatic hyperplasia and prostate cancer are important public health issues. However, histologic markers for these diseases are limited. METHODS: Immunocytochemistry was used to analyze the cellular localization of AIbZIP, Cdc47, androgen receptor and estrogen receptor-beta markers. AIbZIP is a protein recently found to be more abundant in prostate cancer than in benign prostatic tissue, and Cdc47 is a cell proliferation-associated protein. The localization and modulation of androgen receptor and estrogen receptor-beta through the carcinogenesis process have been examined in several studies but controversial results were obtained. These four proteins were evaluated as potential markers of prostatic diseases in 210 needle core biopsies, including normal prostate, benign prostatic hyperplasia, low-grade and high-grade prostatic intraepithelial neoplasia, and different Gleason grades of prostatic adenocarcinoma. RESULTS: Androgen receptor and estrogen receptor-beta do not discriminate between benign and malignant specimens, while AIbZIP was able to distinguish between them. Cdc47, in contrast, discriminated not only between malignant and benign prostatic tissue, but also between benign prostatic hyperplasia and normal prostatic tissue. CONCLUSIONS: Cdc47 appears to be a sensitive marker of prostatic diseases since its expression gradually increased in parallel with the severity of the lesion. AIbZIP discriminated between benign tissue and cancer. AIbZIP and Cdc47 thus appear to be useful markers with diagnostic and prognostic values. PMID- 17270659 TI - Extrapulmonary small cell carcinoma. PMID- 17270661 TI - Extrapulmonary small cell carcinoma of the bladder. AB - Among the many sites for primary small cell cancer is the genitourinary system. The majority of cases have been observed in the bladder and prostate. Small cell carcinoma accounts for less than 1% of all bladder tumors. Definitive predisposing factors are unknown; however, small cell carcinoma of the bladder has been associated with cigarette smoking, long-standing cystitis, bladder calculus, and augmented cystoplasty. Contrary to the early theory of derivation from Kulchitsky cells, it is now believed that small cell carcinoma of the bladder originates from the totipotent stem cells present in the submucosa of the bladder wall. A number of chromosomal aberrations have been reported in small cell cancer of the bladder. There are no specific clinical features that differentiate these patients from transitional cell carcinoma of the bladder; however, some patients may have associated paraneoplastic conditions. Diagnosis is established by cystoscopic-assisted biopsy. Like small cell carcinoma of the lung, small cell carcinoma of the bladder has a propensity for early metastases. There is no standard therapy for small cell carcinoma of the bladder and the prognosis is poor; however, patients treated with cisplatin-based chemotherapy regimens seem to have a better prognosis. PMID- 17270660 TI - Small cell carcinoma of the head and neck: a review. AB - Small cell carcinoma (SCC) has become recognized as a distinct, though relatively infrequent, clinical pathology that occurs in multiple sites throughout the head and neck. Excluding cases that are considered to arise from skin, SCC in the head and neck has been found to develop in nearly all structures associated with the upper aerodigestive tract. Among the head and neck sites, the frequency of SCC is greatest in the larynx, with salivary glands and the sinonasal region comprising the other principle areas of origin. Controversy exist as to whether SCC can develop as a distinct entity in the thyroid, with most tumors that previously would have been considered as SCC now found to be lymphomas or variant forms of other types of thyroid malignancy. While there seems to be some differences among tumors arising from the various subsites, in general all SCC that originate in the head and neck have a tendency for aggressive local invasion and a strong propensity for both regional and distant metastasis. Treatment may include surgical resection, radiotherapy, chemotherapy, or some combination of these modalities. Due to the infrequency of these tumors, it is very unlikely that any large, controlled study will ever be done. For this reason, recommendations for treatment of SCC arising in the head and neck are based primarily on retrospective data from various small case series and on comparative data for treatment of SCC of bronchogenic and other extrapulmonary origin. Although patients with truly limited local disease may enjoy some prolonged survival, most patients with this tumor do poorly despite all current attempts at treatment. PMID- 17270662 TI - Unusual and underappreciated: small cell carcinoma of the prostate. AB - In recent years, attention has focused on the prognostic importance of neuroendocrine differentiation in prostate cancer. Focal neuroendocrine differentiation in prostatic adenocarcinoma is a frequent finding. Though controversial, the prevalence of neuroendocrine cells has been correlated with higher-grade malignancy and poor prognosis. As with other small cell tumors, production of ectopic neuropeptides has been reported. The rarity of the disease has precluded prospective randomized trials. Therapeutic regimens have mainly been modeled after those for small cell lung carcinoma. Here we review the literature to identify potential diagnostic, therapeutic, and prognostic factors. Evident from this review is the necessity for further research in the biology of small cell carcinoma progression, in order to improve therapy. PMID- 17270663 TI - The pathology of extrapulmonary small cell carcinoma. AB - Extrapulmonary small cell carcinomas (EPSCCs) are uncommon malignant neoplasms with a reported incidence of 0.1% to 0.4% in the United States. Since their first description in 1930, they have been seen in nearly every organ system. Like their more common pulmonary counterparts, EPSCCs are thought to arise from a multipotential stem cell. However, there is recent molecular evidence that small cell elements may arise as a late-stage phenomenon in the genetic progression of more organ-typical carcinomas. The morphologic, immunohistochemical, and ultrastructural features are similar to those described in pulmonary small cell carcinomas (PSCCs). The differential diagnosis of EPSCC includes PSCC, other neuroendocrine tumors, small round blue cell tumors, metastatic melanoma, lymphoma, and poorly differentiated non-small cell carcinomas. Molecular alterations reported to occur in EPSCCs include abnormalities described in PSCC and changes found in carcinomas more typically encountered in the organ from which they arise. In this article we discuss the pathology of EPSCC with a review of theories of histogenesis, sites of occurrence, diagnostic features, differential diagnosis, molecular alterations, and clinical behavior. PMID- 17270664 TI - Small cell carcinoma of unknown primary. AB - Small cell carcinoma of unknown primary (SCUP) is an uncommon cancer that is usually diagnosed in the lymph nodes, liver, brain, or bone. Historically, this neoplasm has always been included with extrapulmonary small cell carcinomas (EPSCCs). The true incidence of SCUP is unknown but has been reported to comprise between 7% and 30% of EPSCCs. Although identification of small cell carcinoma can usually be made with histologic examination and immunohistochemical stains, differentiation between primary, metastatic, or other neuroendocrine tumors can be challenging. The prognosis of SCUP varies from a few months to several years depending on the location, extent of disease, and response to therapy. Combination chemotherapy with regimens similar to those used in small cell lung cancer (SCLC) form the backbone of therapy. However, multimodality therapy, including surgery and/or radiation therapy, in addition to chemotherapy may be used to treat localized disease. This review examines the biology, evaluation, and treatment of SCUP. PMID- 17270665 TI - Small cell carcinomas of the gastrointestinal tract: clinicopathological features and treatment approach. AB - Small cell undifferentiated carcinoma (SmCC) of the gastrointestinal tract (GIT) is a rare and highly aggressive malignancy. To date, fewer than 1,000 cases have been reported, with an estimated prevalence of 0.1% to 1% of all gastrointestinal (GI) tumors. Data on the disease are scarce due to its rarity and the fact that most authors have focused on one site within the GIT. In light of the limited data and its perceived similarity to SmCC of the lung, the disease has usually been treated as the latter. Nevertheless, recent clinicopathologic and molecular data imply several differences between the two entities, questioning the extent to which extrapolations from one to the other can be made. We review the available data on GI SmCC with emphasis on outlining its clinicopathologic features and the recommended treatment approach. PMID- 17270666 TI - Merkel cell carcinoma. AB - Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous cancer that predominately affects elderly Caucasians with fair skin and has a propensity for local recurrence and regional lymph node metastases. A variety of terms have been used to describe this tumor, including trabecular cell carcinoma, neuroendocrine or primary small cell carcinoma of the skin, and anaplastic cancer of the skin. Although the skin lesion is most commonly found on sun-exposed areas of the head and neck or extremities, it can occur on the trunk, genitalia, and perianal region. The median age is 69 years, but it may occur earlier and more frequently in immunosuppressed patients. Patients with MCC frequently present with a nonspecific erythematous or violaceous firm nodule or small plaque that may be surrounded by small satellite tumors. MCC usually arises in the dermis and extends into the subcutis. It may be difficult to accurately diagnose MCC by light microscopy alone and ancillary techniques, including electron microscopy and immunohistochemistry, may be necessary to make a definitive diagnosis. Management of MCC is dependent on stage of the disease and is hampered by its rarity and lack of randomized trials. Nonetheless, for localized disease most guidelines include wide local excision of the primary tumor either alone or with radiation therapy. Sentinel lymph node biopsy can be helpful in staging and prognosis, but its benefit in survival remains to be seen. Systemic chemotherapy, akin to regimens for small cell carcinoma of the lung, may be considered as an adjuvant following surgery or to treat locoregional or distant disease. The prognosis of MCC is variable. Some patients with localized disease have an indolent course and are well controlled with local excision alone. On the other hand, many tumors are aggressive and have a tendency for locoregional recurrence and distant metastases. Such patients have a grim prognosis with a median survival of 9 months. Successful outcomes are most often seen in patients with early diagnosis and complete excision. PMID- 17270667 TI - Small cell carcinoma of the female genital tract. AB - Small cell carcinoma (SCC) of the female genital tract is rare, constituting less than 2% of all gynecologic malignancies. It occurs most frequently in the cervix but can also occur in the endometrium, ovary, fallopian tube, vagina, and vulva. SCC of the genital tract is microscopically indistinguishable from that of the lung. Neuroendocrine differentiation is often manifested by a histologic growth pattern, argyrophilia, ultrastructural demonstration of secretory granules, and expression of neuroendocrine markers. Patients with SCC of the female genital tract may be asymptomatic but usually present with localized pain, vaginal bleeding, abdominal bloating or a mass, or symptoms of metastasis disease to the liver, bone, lung, or regional lymph nodes. Ectopic Cushing's syndrome has been reported in SCC of the vagina, and hypercalcemia and inappropriate secretion of antidiuretic hormone have been noted with SCC of the ovary. In general, these tumors have an aggressive clinical course with a propensity for extensive local invasion and distant metastases. Therapy has included surgery, radiation, and chemotherapy akin to those regimens used for SCC of the lung. Although there are no randomized clinical trials, it appears that multimodality therapy is associated with the best results and is the treatment of choice for most patients. Despite aggressive therapy, however, the prognosis for SCC of the female genital tract is poor, with only a minority of patients enjoying a prolonged survival. Indeed, the majority of patients have an early demise with extensive distant disease. We review the clinical features, evaluation, and management of SCC of the female genital tract based on a comprehensive review of the literature. PMID- 17270668 TI - Small cell carcinoma of the breast. AB - Small cell carcinoma of the breast (SCCB) is an uncommon neoplasm that accounts for less than 1% of primary breast cancers. Histologically, these tumors have striking similarities to small call carcinoma of the lung, usually with evidence of associated ductal carcinoma-in-situ (DCIS) with areas of ductal, lobular, or papillary differentiation. Immunoreactivity for neuroendocrine markers is documented in two thirds of cases, while 33% to 50% are positive for estrogen receptor (ER) or progesterone receptor (PR). Her2/neu expression has not been reported in SCCB. Treatment, which may include surgery, radiotherapy, and combination chemotherapy, is based on clinical stage and the presence of metastases. Prognosis is variable and is dependent on the initial stage of disease. PMID- 17270669 TI - Small cell cancer of the pleura, kidney, and thymus. AB - Small cell carcinoma is a distinct clinicopathologic entity that usually arises in the lung but also can originate in extrapulmonary sites, such as the pleura, thymus, and kidney. Small cell carcinoma of the kidney and renal pelvis is rare. Most patients present with large tumors and have evidence of extensive locoregional spread and distant metastases, despite a short duration of symptoms. Although nephrectomy has been used for treatment it does not appear to confer any significant benefit. Cisplatin-based chemotherapy has improved the median survival from 8 months to 20 months. Only isolated cases of small cell carcinoma of the pleura and thymus have been reported. Both tumors have a tendency for aggressive local invasion and distant metastases. Surgery, radiation, and chemotherapy have been used in the management of these tumors with variable results. PMID- 17270670 TI - What is it about pressure that really matters in glaucoma? PMID- 17270671 TI - Early glaucoma detection using the Humphrey Matrix Perimeter, GDx VCC, Stratus OCT, and retinal nerve fiber layer photography. AB - PURPOSE: To compare the effectiveness of Humphrey Matrix perimetry, GDx VCC, Stratus OCT, and retinal nerve fiber layer (RNFL) photography using the Heidelberg Retina Angiograph 1 (HRA1) for early glaucoma detection. DESIGN: Cross sectional comparative study. PARTICIPANTS: Seventy-two primary open-angle glaucoma patients with early-stage visual field defects and 48 healthy controls were included. METHODS: Measurements using Humphrey Matrix perimetry, GDx VCC, Stratus OCT, and RNFL photography using HRA1, as well as standard automated perimetry, were obtained. We constructed receiver operating characteristic (ROC) curves for all available parameters and calculated the area under the ROC curves (AUC) to seek the best discriminating parameter of each test. Subsequently, the ROC curves were calculated for the combinations of the best discriminating parameters of each test to seek the most effective combination for early glaucoma detection. MAIN OUTCOME MEASURE: The AUC for various parameters of Humphrey Matrix perimetry, GDx VCC, Stratus OCT, and RNFL photography using HRA1. RESULTS: The AUCs of Humphrey Matrix perimetry, GDx VCC, Stratus OCT, and RNFL photography using HRA1 with the best discriminating parameter were 0.990, 0.906, 0.794, and 0.751, respectively. The AUC of the following best combination was 0.972, more than 5 points depressed below the level of 5% on the pattern deviation plot from Humphrey Matrix perimetry, and the nerve fiber indicator was larger than 20 from GDx VCC. CONCLUSIONS: The AUC of the Humphrey Matrix perimetry was greater than that of the GDx VCC, Stratus OCT, and RNFL photography using HRA1. PMID- 17270672 TI - Subluxation of suture-fixated posterior chamber intraocular lenses a clinicopathologic study. AB - PURPOSE: To report the occurrence of subluxation of suture-fixated posterior chamber (PC) intraocular lenses (IOL) and elucidate the mechanisms involved. DESIGN: Prospective clinicopathologic study. PARTICIPANTS: A single 10-0 Prolene suture explanted from a patient who experienced subluxation of his PC-IOL, 11.5 years after placement. Furthermore, multiple 10-0 Prolene sutures and PC-IOLs used for iris fixation were studied as controls. METHODS: Scanning electron microscopy (SEM) was used to analyze the surface of the explanted suture. In addition, randomly selected 10-0 Prolene sutures cut with Vannas scissors and cut with the positioning holes of a randomly selected PC-IOL identical to that implanted in the patient's eye were examined as controls. Finally, the positioning holes of several randomly selected, iris-fixated PC-IOLs were studied using SEM with particular attention to surface quality and edge finish. MAIN OUTCOME MEASURES: Presence of any signs of suture degradation, the character of the cut edge of the suture, as well as the characteristics of the positioning holes of the PC-IOLs. RESULTS: Scanning electron microscopy of the explanted suture revealed sharply cut edges, without significant degradation of the suture, and no intact loop. Scanning electron microscopy of the control suture cut with a PC-IOL demonstrated a similarly cut edge. The positioning holes of the examined PC-IOLs had a sharp edge, and some also had an imperfect finish. CONCLUSION: We conclude that the surface properties of the positioning holes lead to cutting of the suture, and subsequent subluxation of the PC-IOL. PMID- 17270673 TI - Association between vision loss and higher medical care costs in Medicare beneficiaries costs are greater for those with progressive vision loss. AB - PURPOSE: To identify the cost to the Medicare program for patients with either stable or progressive vision loss and to estimate the impact on eye-related and non-eye related care. DESIGN: Retrospective cohort study. PARTICIPANTS: The study population was Medicare beneficiaries included in the standard 5% analytic sample and continuously enrolled from 1999 to 2003, excluding Medicare managed-care enrollees. METHODS: Vision loss was categorized as moderate loss, severe loss, and blindness, based on International Classification of Diseases 9, Clinical Modification codes. MAIN OUTCOME MEASURES: Average yearly cost of eye-related and non-eye related medical care during 1999 to 2003, in 2003 dollars. SECONDARY OUTCOMES: (1) depression, (2) injury, (3) skilled nursing facility (SNF) utilization, and (4) long-term care facility (LTC) admission. RESULTS: Compared with patients with normal vision, excess adjusted mean eye-related costs were 345 dollars, 407 dollars, and 237 dollars annually for those with moderate loss, severe loss, and blindness, respectively; annual excess non-eye related costs were 2193 dollars, 3301 dollars, and 4443 dollars, respectively. At each level of vision loss, those progressing from a presumably normal state at baseline incurred higher Medicare costs than those with that level of vision loss at baseline. Any degree of progressive vision loss was associated with an increased risk of depression, injury, SNF utilization, and LTC admission. Identifiable costs attributable to these complications explained 27% to 41% of the excess costs associated with vision loss. CONCLUSIONS: Medicare beneficiaries with coded diagnoses of vision loss incur significantly higher costs than those with normal vision, and approximately 90% of these costs are non-eye related medical costs. Extrapolating to the entire Medicare population, blindness and vision loss are associated with $2.14 billion in 2003 non-eye related medical costs. Preventing vision loss is not only a medical imperative but also an economic one. PMID- 17270674 TI - Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. AB - OBJECTIVE: An examination of clinically relevant subgroups of patients in the MARINA study of ranibizumab in treatment of minimally classic or occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) was done. Objectives were to determine the effectiveness of ranibizumab across subgroups, compare the effectiveness of ranibizumab with that of sham injection within subgroups, and evaluate the relationship between selected baseline characteristics and visual acuity (VA) outcomes. DESIGN: Retrospective subgroup analyses of 24-month data from the MARINA study. PARTICIPANTS AND CONTROLS: Seven hundred sixteen patients were randomly assigned to 0.3 mg ranibizumab (n = 238), 0.5 mg ranibizumab (n = 240), or sham treatment (n = 238). METHODS: Efficacy outcomes were compared across subgroups based on patients' gender, age, baseline VA score, baseline CNV lesion size, CNV lesion type, and duration of neovascular AMD using univariate analyses. Multivariate analyses were performed on the change from baseline to 24 months in VA score to assess further the correlation between baseline characteristics and VA outcome. MAIN OUTCOME MEASURES: Proportion of patients losing <15 letters from baseline, proportion gaining > or =15 letters from baseline, and mean VA score change from baseline. RESULTS: For each of the 3 VA end points, all subgroups of ranibizumab treated patients did better on average than the sham-treated patients. Increasing age, larger CNV lesion size at baseline, and a higher baseline VA score were all associated with greater loss of letters in the sham group or less gain of letters in the ranibizumab groups. However, the net benefit of ranibizumab versus sham treatment was greater in patients who scored higher than in those who scored lower in baseline VA. CONCLUSIONS: This subgroup analysis of 24-month data from the MARINA study indicates that ranibizumab treatment was associated with an average increase from baseline VA in all subgroups evaluated, and that ranibizumab treatment was superior to sham treatment across all subgroups. The most important predictors of VA outcomes were, in decreasing order of importance, baseline VA score, CNV lesion size, and age. PMID- 17270675 TI - Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. AB - PURPOSE: To describe the 15-year cumulative incidence of signs of early and late age-related macular degeneration (AMD). DESIGN: Population-based cohort study. PARTICIPANTS: We included 3917 persons, 43 to 86 years of age at the time of a baseline examination in 1988 through 1990 and with information collected in follow-up in 1993 through 1995, and/or 1998 through 2000, and/or 2003 through 2005. METHODS: Grading of stereoscopic fundus photographs using the Wisconsin Age Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Cumulative incidence of drusen type and size, pigmentary abnormalities, geographic atrophy, and exudative AMD accounting for competing risk of death. RESULTS: The 15-year cumulative incidence was 14.3% for early AMD (the presence of either soft indistinct drusen or the presence of pigmentary abnormalities together with any type of drusen) and 3.1% for late AMD (presence of exudative AMD or geographic atrophy). There was an increased incidence of AMD lesions with age (P<0.05). Individuals > or = 75 years of age at baseline had significantly (P<0.01) higher 15-year incidences of the following characteristics than people 43 to 54 years of age: larger drusen (125 mum in diameter, 24.1% vs 10.6%), soft indistinct drusen (18.7% vs 6.5%), retinal pigmentary abnormalities (20.2% vs 3.7%), exudative macular degeneration (4.4% vs 0.4%), and pure geographic atrophy (3.2% vs 0%). Controlling for age, compared with those with small numbers of only small hard drusen (1-2), those with large numbers of only hard drusen (> or =8) had an increased 15-year age-adjusted incidence of both soft indistinct drusen (16.3% vs 4.7%) and pigmentary abnormalities (10.6% vs 2.7%). Eyes with soft indistinct drusen or pigmentary abnormalities at baseline were more likely to develop late AMD at follow-up than eyes without these lesions (17.8% vs 1.2% and 12.9% vs 1.7%, respectively). CONCLUSIONS: We document the long-term incidence of signs of AMD and a continuum from small hard drusen to late AMD in older persons in the population. The 15-year cumulative incidence of late AMD in people > or = 75 years of age (8%) indicates a public health problem of significant proportions because the United States population this age is expected to increase by 54% between 2005 and 2025. PMID- 17270676 TI - The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. AB - PURPOSE: To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA. DESIGN: Prospective natural history study of GA resulting from age-related macular degeneration. PARTICIPANTS: Two hundred twelve eyes of 131 patients were included in the analysis. METHODS: Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined. MAIN OUTCOME MEASURE: Rate of enlargement of the atrophy. RESULTS: The median overall enlargement rate was 2.1 mm2/year (mean, 2.6 mm2/year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (alpha, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye. CONCLUSIONS: Treatment trials for GA with an outcome variable of change in enlargement rate are feasible. PMID- 17270677 TI - Cataract surgery is associated with a higher rate of photodynamic therapy for age related macular degeneration. AB - PURPOSE: To investigate the association between cataract surgery and the rate of photodynamic therapy (PDT) for age-related macular degeneration (AMD). DESIGN: Observational population-based retrospective case-control study. PARTICIPANTS: All members in a district of the largest health maintenance organization (HMO) in Israel > 50 years old on January 1, 2001, who did not terminate their membership through May 31, 2005 (139 894 members). METHODS: All PDT procedures for AMD performed in the study population between January 1, 2001 and May 31, 2005 (283 patients) and all cataract surgeries performed between January 1, 2001 and December 31, 2003 (5913 patients) were documented. We extracted clinical information from the chronic disease registry of the HMO as well as demographic and socioeconomic information. For each patient that underwent cataract surgery, 5 HMO members matched in age, gender, chronic diseases (systemic hypertension, diabetes, hyperlipemia, and ischemic heart disease), place of residence, country of birth and socioeconomic status, who did not undergo cataract surgery, were randomly chosen as controls (n = 29 565). MAIN OUTCOME MEASURES: The rate for undergoing PDT at different time periods after cataract surgery. RESULTS: Fifty (0.85%) cataract patients and 94 control cases (0.32%) underwent PDT after cataract surgery (P<0.0001, chi-square test). A significant rise in PDT rate was noticed in cataract patients compared to controls during the first 6 months after surgery (P = 0.004, chi-square test). Between 6 and 12 months postoperatively, the PDT rates were similar in both groups. However, a more significant rise in PDT rates occurred between 1 and 1.5 years after surgery (P<0.0001, chi-square test). The Kaplan-Meier PDT-free survival curve of cataract patients was significantly worse than that of the controls (P<0.0001, chi-square test; P = 33.7, log-rank test). The hazard ratio for cataract patients compared to controls to undergo PDT after surgery was 2.7 (confidence interval = 2.4-5.7). The most significant factors to reduce the time to PDT were advanced age followed by having had cataract surgery, place of birth, socioeconomic status, and hyperlipidemia (Cox proportional hazards survival regression). CONCLUSIONS: We identified an increased rate of PDT, presumably for subfoveal AMD, 1 to 1.5 years after cataract surgery. PMID- 17270678 TI - Depression and anxiety in visually impaired older people. AB - PURPOSE: To investigate the association between visual impairment and depression and anxiety in older people in Britain. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Thirteen thousand nine hundred people aged 75 years and older in 49 family practices in Britain. METHODS: Vision was measured in 13 900 people aged 75 years and older in 49 family practices taking part in a randomized trial of health screening that included depression (Geriatric Depression Scale [GDS-15]) and anxiety (General Health Questionnaire [GHQ-28]). Cause of visual impairment (binocular acuity less than 6/18) was assessed from medical records. Analysis was by logistic regression (odds ratio [OR] and 95% confidence interval [CI]), taking account of potential health and social confounders. MAIN OUTCOME MEASURES: Levels of depression and anxiety. RESULTS: Visually impaired people had a higher prevalence of depression compared with people with good vision. Of visually impaired older people, 13.5% were depressed (GDS-15 score of 6 or more) compared with 4.6% of people with good vision (age- and gender-adjusted OR, 2.69; 95% CI, 2.03-3.56). Controlling for potential confounding factors, particularly activities of daily living, markedly attenuated the association between visual impairment and depression (OR, 1.26; 95% CI, 0.94-1.70). There was little evidence for any association between visual impairment and anxiety. On the GHQ-28 scale, 9.3% of visually impaired people had 2 or more symptoms of anxiety compared with 7.4% of people with good vision. CONCLUSIONS: Although cause and effect cannot be established in a cross-sectional study, it is plausible that people with visual impairment are more likely to experience problems with functioning, which in turn leads to depression. PMID- 17270679 TI - Reduced incidence of intraoperative complications in a multicenter controlled clinical trial of triamcinolone in vitrectomy. AB - PURPOSE: To evaluate the benefits and potential complications of using triamcinolone acetonide (TA) in pars plana vitrectomy (PPV). DESIGN: Multicenter, prospective, controlled clinical trial. PARTICIPANTS: In total, 774 patients from 8 Japanese hospitals were enrolled, with 391 patients undergoing TA-assisted PPV and 383 control patients undergoing conventional PPV. INTERVENTION: Intraoperative use of TA to aid visualization of the vitreous. MAIN OUTCOME MEASURES: The incidence of intraoperative complications, including retinal breaks, was evaluated. Early postoperative complications, intraocular pressure (IOP), and adverse events occurring within 3 months of the operation were also monitored. RESULTS: The incidence of both retinal breaks and intraoperative retinal detachment was significantly lower in TA-assisted PPV than in conventional PPV. Retinal breaks were seen in 34 eyes (8.7%) undergoing TA assisted PPV compared with 54 eyes (14.1%) undergoing conventional PPV (odds ratio [OR], 0.603; 95% confidence interval [CI], 0.381-0.955; P = 0.031). Retinal detachment was seen in only 3 eyes (0.8%) in which TA was used compared with 14 eyes (3.7%) in which TA was not used (OR, 0.204; 95% CI, 0.057-0.727; P = 0.014). In total, 388 eyes in the TA-assisted PPV group (99.2%) and 374 eyes in the conventional PPV group (97.6%) were followed up for 3 months after the operation. Although the mean postoperative IOPs were comparable in both groups, antiglaucoma eye drops were used more frequently by patients in the TA-assisted group than by those in the conventional PPV group (OR, 1.673; 95% CI, 1.126-2.484; P = 0.011). No serious adverse events, such as endophthalmitis or retinal degeneration, were observed in either group. CONCLUSIONS: Intraoperative use of TA reduced the incidence of retinal breaks and retinal detachments in eyes undergoing PPV. There were no serious adverse events related to the intraoperative use of TA. Although antiglaucoma eye drops were required more frequently after TA-assisted PPV than after conventional PPV, IOP was well-controlled in both groups. PMID- 17270680 TI - Retinopathy of prematurity in assisted versus natural conception and singleton versus multiple births. AB - OBJECTIVES: To determine whether the incidence and severity of retinopathy of prematurity (ROP) differs between infants conceived naturally and those born after assisted conception, and to analyze the impact of singleton versus multiple gestation on ROP. DESIGN: Comparative case series. PARTICIPANTS: The study group consisted of 363 infants with a birth weight (BW) of < or =1500 g who were hospitalized in the neonatal unit of a single tertiary-care center between 1998 and 2000. METHODS: Data on gestational age (GA), BW, type of pregnancy (singleton/multiple), and type of conception (natural/assisted) were recorded, in addition to the ophthalmological results. Ophthalmological examinations were performed routinely at 4 weeks and repeated later, depending on the severity of the findings. MAIN OUTCOME MEASURES: Presence and stage of ROP were compared between infants conceived naturally and those conceived by assisted technology, and between singleton and multiple-birth infants. RESULTS: Mean GA at birth was 29.4 weeks (standard deviation, 2.5; range, 23-36). Two hundred four neonates (56.2%) were conceived naturally and 159 were conceived by assisted conception, either in vitro fertilization (IVF) alone (n = 119 [32.85%]) or IVF combined with drug treatment (n = 40 [11%]). Sixty-four infants in the natural conception group were the product of multiple pregnancies, as were 103 infants in the assisted conception group. Retinopathy of prematurity was noted in 159 of 363 infants (43.8%): 89 conceived naturally (71% singletons, 28% twins, and 17% triplets) and 70 born by assisted conception (70% singletons, 47% twins, and 33% triplets). There was no significant difference in either occurrence or severity of ROP between the natural conception and assisted conception groups. Singletons had a significantly higher rate of advanced ROP (stages II-III) (30.2%) than twins (23.1%), triplets, and quadruplets (10.6%) (P = 0.024). On multiple regression analysis, low GA and BW were the variables most significantly associated with ROP. CONCLUSIONS: In our sample, assisted conception per se did not appear to be a risk factor for ROP. Singleton babies with a birth weight of < or =1500 g were more prone to develop ROP stages II and III than twins or triplets. Gestational age and BW were the most significant factors associated with ROP. PMID- 17270681 TI - Intravitreal triamcinolone acetonide for the treatment of immune recovery uveitis macular edema. AB - PURPOSE: To evaluate the use of intravitreal triamcinolone (IVTA) for the treatment of macular edema secondary to immune recovery uveitis (IRU) in patients with AIDS. DESIGN: Prospective, consecutive, interventional case series. PARTICIPANTS: Eight eyes of 7 patients receiving 13 injections. METHODS: Prospective, consecutive, interventional case series of 13 injections involving 8 eyes in 7 patients who underwent an intravitreal injection of 20 mg decanted triamcinolone acetate for fluorescein angiographically proven IRU-related macular edema. MAIN OUTCOME MEASURES: The primary outcome measure was vision (using the Early Treatment Diabetic Retinopathy Study chart). Other outcome measures included fluorescein angiography and optical coherence tomography. RESULTS: Visual acuity improved at all time points and was statistically significant at the 1-month and 3-month follow-up examinations. The average visual improvement was 3 lines at 3 months. Retinal volume and thickness improvement were statistically significant at all time points. All patients had a minimum follow up of 9 months, and there were no cases of cytomegalovirus reactivation. CONCLUSIONS: Previous studies showed that treatment with sub-Tenon repository steroids for the treatment of macular edema of IRU was only marginally effective. However, the current study shows that IVTA can be an effective short-term treatment for macular edema secondary to IRU in patients with AIDS. Longer follow up is needed to assess the durability of the effect and to monitor for longer term complications and outcomes. PMID- 17270682 TI - Vitrectomy and release of presumed epipapillary vitreous traction for treatment of nonarteritic anterior ischemic optic neuropathy associated with partial posterior vitreous detachment. AB - OBJECTIVE: To study the results of vitrectomy and release of epipapillary vitreous adhesions for the treatment of nonarteritic anterior ischemic optic neuropathy (NAION) associated with partial posterior vitreous detachment (PVD). DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: A series of 16 patients with clinical picture of NAION and small discs associated with partial PVD, diagnosed clinically and confirmed by optical coherence tomography and B-scan ultrasonography. INTERVENTION: All patients underwent standard pars plana vitrectomy with meticulous removal of epipapillary vitreous adhesions within 1 month from the onset of visual symptoms. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), mean deviation of visual fields, and color vision testing. RESULTS: In 15 patients BCVA improved (93.7%), mean preoperative BCVA was 6/38 (0.82+/-0.53 logarithm of the minimum angle of resolution [logMAR]), which improved to 6/18 (0.49+/-0.37 logMAR) postoperatively at 3 months. Nine eyes (56%) had > or =3 lines of visual improvement. Visual fields improved in 4 patients and color vision improved in 1 patient. CONCLUSION: Vitreous traction from partial PVD may have a causative role in some cases of NAION associated with small discs. In these cases, vitrectomy and removal of epipapillary vitreous may result in improvement of visual acuity. PMID- 17270683 TI - Outcome of treated orbital cellulitis in a tertiary eye care center in the middle East. AB - PURPOSE: To describe risk factors predisposing patients to orbital cellulitis and potential complications in patients treated at a tertiary eye care referral center in the Middle East. DESIGN: Noncomparative, interventional, retrospective case series. PARTICIPANTS: Patients diagnosed with orbital cellulitis. METHODS: A 15-year clinical review of patients with a diagnosis of orbital cellulitis referred to King Khaled Eye Specialist Hospital, an accredited (Joint Council on Accreditation of Healthcare Organizations, Washington, DC) tertiary care center in Riyadh, Saudi Arabia, was performed. Only those patients who had clinical signs and symptoms or radiologic evidence suggestive of orbital cellulitis were included in the study. MAIN OUTCOME MEASURES: Patient demographics, factors predisposing to orbital cellulitis, and resulting complications. RESULTS: A total of 218 patients (136 male, 82 female) fulfilling the diagnostic criteria for orbital cellulitis were identified. The average age of these patients was 25.7 years (range, 1 month-85 years). On imaging studies, there was evidence of inflammatory or infective changes to orbital structures; orbital abscesses were identified in 116 patients (53%). Sinus disease was the most common predisposing cause in 86 patients (39.4%), followed by trauma in 43 patients (19.7%). All patients received systemic antibiotic treatment before the identification of any responsible organisms. Of the 116 patients with orbital abscess, 101 patients (87%) required drainage. The results of cultures in patients in whom an orbital abscess was drained were positive for 91 patients (90%). The most common microorganisms isolated from the drained abscesses were Staphylococci and Streptococci species. Blood cultures were positive in only 4 patients from whom blood was drawn for cultures. Visual acuity improved in 34 eyes (16.1%) and worsened in 13 eyes (6.2%), including 9 (4.3%) eyes that sustained complete loss of vision, which was attributed to the delay in correct diagnosis and timely intervention (average 28 days vs. 9 days in patients with no loss of vision; P<0.05). There were 9 cases of intracranial extension of orbital abscesses that required either extended treatment with systemic antibiotics alone or in combination with neurosurgical intervention. Most patients received oral antibiotics on discharge for varying periods. There were 6 cases (2.7%) of strabismus and 4 cases (1.8%) of ptosis that persisted after treatment and resolution of orbital cellulitis. CONCLUSIONS: Untreated sinusitis and prior history of orbital trauma were the 2 major causes of orbital cellulitis in patients referred to a tertiary care eye center in the Middle East. Although rare, severe visual loss still remains a serious complication of delayed detection and intervention in most cases of orbital cellulitis. PMID- 17270684 TI - Drug-induced ectropion: what is best practice? AB - PURPOSE: To review cases of possible drug-induced ectropion and recommend what we consider to be best practice. DESIGN: Retrospective observational case series. PARTICIPANTS: Thirteen consecutive outpatients. METHODS: Records of 13 outpatients on topical medication presenting with topical drug-induced ectropion were retrospectively analyzed. MAIN OUTCOME MEASURES: Eyelid position, topical agent causing the allergy, and medical and surgical management options. RESULTS: In all 13 patients, the ectropion resolved partially or completely after discontinuing the offending topical agent. Dorzolamide (53%) was the most common offending agent, followed by brimonidine (23%). One of the 13 patients underwent failed ectropion surgery correction before referral, but improved once the topical agent was discontinued. Two of the patients successfully underwent surgical correction for ectropion after discontinuing their topical therapy. Those patients who discontinued the topical therapy and had a short course of steroid therapy did not require surgical correction. CONCLUSIONS: This study demonstrates that sensitivity to topical agents can induce ectropion in more than 1 manner. Chronic exposure to the causative agent leads to cicatricial changes in the anterior lamella of the eyelid in susceptible individuals, and can manifest as contact dermatitis leading to tissue edema and mechanical ectropion. Early recognition of this condition and discontinuation of therapy is of paramount importance; it may lead to complete resolution. Topical steroids are a necessary adjunct in the management of drug-induced ectropion. Based on our experience, we propose a management algorithm for drug-induced ectropion. PMID- 17270685 TI - Experience with the polymer-coated hydroxyapatite implant after enucleation in 126 patients. AB - OBJECTIVE: To evaluate the new polymer-coated hydroxyapatite implant. DESIGN: Retrospective nonrandomized single-center case series. PARTICIPANTS: One hundred twenty-six patients managed with enucleation and placement of the polymer-coated hydroxyapatite implant at the Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University. METHODS: A retrospective analysis was performed on 126 patients managed with enucleation and placement of the polymer-coated hydroxyapatite implant. MAIN OUTCOME MEASURES: Ease of placement, functional ocular motility, tissue complications, and patient satisfaction. RESULTS: The preenucleation diagnoses included uveal melanoma (n = 76; 61%), retinoblastoma (n = 34; 27%), blind painful eye (n = 8; 6%), neovascular glaucoma from intraocular tumors or retinal detachment (n = 5; 4%), and others (n = 3; 2%). Previous ocular therapies for posterior segment conditions such as plaque radiotherapy, retinal detachment repair, and chemoreduction, thermotherapy, and cryotherapy had been performed in 22% of patients (n = 27). The implant size was 20 mm (n = 103; 82%), 18 mm (n = 22; 17%), and 16 mm (n = 1; 1%). Implant preparation and placement was uncomplicated in all patients, without adhesion to surrounding tissue. Four rectus muscles were attached to the implant in all patients. Socket motility was judged to be good (n = 118; 94%), fair (n = 6; 5%), and poor (n = 2; 2%). Complications included conjunctival thinning (n = 1; <1%), pyogenic granuloma (n = 1; <1%), conjunctival cyst (n = 3; 2%), implant infection (n = 1; <1%), and implant exposure (n = 3; 2%). There were no cases of implant extrusion or allergic reaction to the polymer. Patient satisfaction was reported as good (n = 123; 98%), fair (n = 2; 2%), and poor (n = 1; <1%). CONCLUSIONS: The polymer coated hydroxyapatite implant is smoothly placed into the orbit after enucleation without the need for additional tissue wrap. With proper placement, this implant provides satisfactory functional motility and shows favorable tissue tolerance with no clinical evidence of allergic reaction or extrusion. PMID- 17270686 TI - Discrepancies between intraocular lens implant power prediction formulas in pediatric patients. AB - PURPOSE: The SRK II, SRK/T, Holladay I, and Hoffer Q intraocular lens power prediction formulas have been claimed to be interchangeable in their predicted postoperative refractive outcome among pediatric patients. In this study, we evaluated this clinical perception. DESIGN: Mathematical analysis. METHODS: Analytical prediction of implant power using keratometry values up to 55 diopters and axial length values as short as 16 mm was performed for 2 different refractive goals using the optimized intraocular lens constants for the SRK II, SRK/T, Holladay I, Hoffer Q, and Haigis formulas. Comparison graphs for the predicted implant power of each formula were constructed and differences between predicted results of the formulas were plotted. MAIN OUTCOME MEASURE: Predicted implant power. RESULTS: Significant differences in intraocular lens power prediction were found among the Hoffer Q, Holladay I, and SRK II formulas in the pediatric range of axial length and keratometry values. The Holladay I and Haigis formulas were found to be similar in their intraocular lens power prediction. The SRK/T was comparable with the Holladay I and Haigis formulas, but still differed in the high keratometry values. CONCLUSIONS: This analysis demonstrates differences in the intraocular lens power prediction among commonly used formulas for axial length and keratometry values in the pediatric range. It is unclear under what circumstances each of these formulas may be preferred in the pediatric population. PMID- 17270687 TI - Open-angle glaucoma and cardiovascular mortality. PMID- 17270688 TI - Graves' orbitopathy. PMID- 17270689 TI - Timing of surgery for Graves' orbitopathy. PMID- 17270691 TI - Ocular surface reconstruction. PMID- 17270693 TI - Ectasia after photorefractive keratectomy. PMID- 17270694 TI - Acanthamoeba keratitis. PMID- 17270696 TI - Ectasia after photorefractive keratectomy. PMID- 17270697 TI - Secondary cataract prevention. PMID- 17270698 TI - Screening and diabetes mellitus. PMID- 17270701 TI - Intravitreal bevacizumab. PMID- 17270702 TI - Pneumatic retinopexy. PMID- 17270703 TI - Macular thickening in acute anterior uveitis. PMID- 17270704 TI - Complementary suppression of T cell activation by peritoneal macrophages and CTLA 4-Ig. AB - Peritoneal macrophages suppressed T lymphocyte activation by amino acid catabolism. CTLA-4-Ig complemented this form of suppression by blocking the costimulation of T cells. Inhibition of the amino acid catabolizing enzymes or blockade of the IFNgamma signaling essential for macrophage-mediated suppression did not impact CTLA-4-Ig efficacy. Except for phytohemagglutinin, T cell responses to superantigen, mitogen, and anti-CD3 were further reduced when CTLA-4 Ig was combined with peritoneal macrophages. The combination of these complimentary forms of immune regulation potently suppresses adaptive immunity. PMID- 17270706 TI - Immunobiological changes of in vivo glucocorticoid depleted male Swiss albino rats. AB - Whether endogenous deficiency of adrenal corticosteroid by unilateral adrenalectomy leads to any modulation of macrophage response is not clear and needs investigation in detail. We performed unilateral adrenalectomy on male Swiss albino rats. Fractions of splenic macrophages were isolated and their functional activities were determined. To test the effect of adrenal hormone insufficiency (after unilateral adrenalectomy) on the cell mediated and humoral immune response, sheep red blood cells were injected, then the delayed type hypersensitivity (DTH) response and the number of antibody secreting plasma cells were determined. Studies reported herein indicate that in vivo glucocorticoid (GC) insufficiency due to unilateral adrenalectomy decreases chemotactic migration, myeloperoxidase enzyme release, and lysozyme release from rat splenic macrophages that were also related to the induction of cell mediated and humoral immune responses. The maximum number of plaque was obtained from control cells isolated from spleen after 10 days from the control rats, whereas the number of plaque was decreased in spleens isolated 20 days after unilateral adrenalectomy. Our study also showed time dependent decrease in foot pad swelling in the unilaterally adrenalectomized rats where endogenous GC was reduced with respect to control indicating reduced DTH response in case of GC insufficiency. We found slower clearance of bacterial burden from the blood and spleen isolated from unilaterally adrenalectomized rats with respect to control. Thus on one hand partially GC insufficient animals show altered macrophage response and on the other hand it heightens the persistence (in vivo) of Staphylococus aureus. The study may be helpful in understanding that adrenal corticosteroid insufficiency due to adrenalectomy interferes with immune functions, which may also support the hypothesis that endogenous GC plays a role in regulating immune response. PMID- 17270705 TI - Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice. AB - Experimental autoimmune uveoretinitis (EAU) serves as a model of human endogeneous uveitis. In the present study we examined whether induction of heat shock protein (HSP) 70 by oral geranylgeranylacetone (GGA) administration had a therapeutic effect on murine EAU. When C57BL/6 mice that had received oral administration of GGA (500mg/kg) were immunized with interphotoreceptor retinoid binding protein (IRBP)-derived peptide plus adjuvants, the expression levels of HSP70 mRNA and protein were rapidly and transiently upregulated in eyes of the GGA-treated mice, compared with those from vehicle-pretreated and IRBP-immunized mice. The antigen-specific T cell proliferation was partially suppressed in these mice treated with GGA. The mean EAU scores of the GGA-treated mice on day 21 and 28 (2.4+/-0.2 and 2.1+/-0.2, respectively) were significantly lower than those in the controls (3.0+/-0.1 and 2.6+/-0.2, respectively p<0.01). The histopathological severity of the GGA-treated mice (average 0.33) was markedly milder than that in the controls (average 1.63, p<0.05) at day 21. The present findings demonstrate that the pharmacological induction of HSP70 may be applicable to the amelioration of ocular autoimmune diseases. PMID- 17270707 TI - The detection of ADAM8 protein on cells of the human immune system and the demonstration of its expression on peripheral blood B cells, dendritic cells and monocyte subsets. AB - A disintegrin and metalloprotease (ADAM) proteins have wide ranging functions, including proteolytic cleavage of cell surface molecules, cell fusion, cell adhesion and intracellular signalling. Recent evidence suggests the involvement of ADAM8 in allergic responses. For instance, ADAM8 is amongst a number of genes up-regulated in experimentally induced asthma in animals. In order to further define the involvement of ADAM8 in allergic responses, we sought in the first instance to examine its distribution on human peripheral blood B cells, resting and activated T cells, monocyte subsets and monocyte derived dendritic cells. Here we demonstrate for the first time ADAM8 protein expression on B cells and dendritic cells, and its higher expression on CD14(2+)CD16(-) monocytes compared to CD14(+)CD16(+) cells. Immature dendritic cells expressed low levels of ADAM8 when treated with a combination of GM-CSF and IL-4, but stimulation with LPS resulted in a higher level of expression, which was TLR-4 independent. Up regulation of ADAM8 expression on dendritic cells was also observed after stimulation with TNF-alpha, but not after stimulation with anti-CD40. The demonstration of ADAM8 expression on these cells provides an opportunity for addressing the potential role of inhaled protease allergens, such as Der p 1, in modulating ADAM8 functions, particularly with regards to innate immune responses by dendritic cells and IgE synthesis by B cells. PMID- 17270708 TI - Immuno-electron microscopic localisation of caveolin 1 in human placenta. AB - We have localised the placental endothelial marker caveolin-1 at the ultrastructural level using indirect immunogold labelling. The particulate label has been quantified to assess the distribution of the target protein within term placental chorionic villi. The mesodermal compartment of the tissue was more heavily labelled than the ectodermally derived trophoblast. Basal plate lining endothelium and villous endothelium had similar immunoreactivity with anti caveolin-1 antibody. A polarised distribution of the caveolin within chorionic villous capillary endothelial cells was observed. As evidenced by immuno reactivity, the protein was statistically significantly more concentrated in the region associated with the basal membrane than the apical membrane. The latter region contained in turn significantly more anti-caveolin-1 immunoreactivity than the central region. These differences are discussed in the light of possible transport and signalling platform roles for villous and basal plate endothelium. PMID- 17270709 TI - Stimulation of Vgamma9/Vdelta2 T-lymphocyte proliferation by the isoprenoid precursor, (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate. AB - (E)-1-Hydroxy-2-methyl-but-2-enyl 4-diphosphate, a recently discovered intermediate in the deoxyxylulose phosphate pathway of isoprenoid biosynthesis, has been shown to act as a potent immunomodulator. In cultures of human peripheral blood mononuclear cells from eight non-related donors, the compound stimulated the proliferation of Vgamma9/Vdelta2 T lymphocytes with a median EC(50) of 70 pM when 10 U/ml of IL-2 was used as costimulant. Isopentenyl diphosphate (IPP), dimethylallyl diphosphate (DMAPP) and some structural analogs of (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate also stimulated Vgamma9/Vdelta2 T-cell proliferation, albeit at much higher concentrations. The Vgamma9/Vdelta2 T-cell proliferation is highly dependent on the seeding density used in culture. All phosphoantigens tested elicited the proliferation of two T lymphocyte populations with different apparent ratios between the expression level of Vdelta2 and Vgamma9 chains. PMID- 17270710 TI - Insights into the immunogenetic basis of two ganglioside-associated idiotypic networks. AB - The heavy-chain variable regions (VH) from 14F7 MAb, an IgG1 antibody specific for GM3(NeuGc) ganglioside, and its anti-idiotype, the 4G9 MAb, were cloned and sequenced. Comparison with previously reported sequences showed that VH 14F7 belongs to the J558(VHI) gene family and that it is highly mutated. VH 4G9 belongs to the Q52(VHII) gene family. The HCDR3 14F7 sequence contains three basic residues that could be involved in the binding to 4G9 MAb, which bears acidic residues in its HCDR3. Studies performed in the syngeneic model showed that 14F7 MAb requires both coupling to KLH and the use of Freund's adjuvant to induce an effective anti-idiotypic IgG (Ab2) response. In contrast, P3 MAb, a germline gene-encoded Ab1 that also recognizes the GM3(NeuGc) ganglioside through a basic motif in its H-CDRs, has been reported to be immunogenic in syngeneic mice, even when injected in saline. In addition, when Leghorn chickens were immunized with 14F7 or P3 MAbs emulsified in Freund's adjuvant, only P3-immunized animals were able to develop antibodies that recognized NeuGc-containing gangliosides, antigens which are not present in the normal tissues of this animal species. This phenomenon could be due to the lack of idiotypic connectivity of 14F7MAb. PMID- 17270712 TI - Applications of lipopolysaccharide derived from Pantoea agglomerans (IP-PA1) for health care based on macrophage network theory. AB - Innate immunity is a universal prophylactic system which all multi-cellular animals possess. Macrophages are the cells that play the central role in the innate immune system. In 1991, we discovered a substance in a water extract of wheat flour that activated macrophages after oral or intradermal administration. The active substance was lipopolysaccharide (LPS), which is derived from the cell walls of Pantoea agglomerans, gram-negative bacteria that grows symbiotically with wheat. We named the substance IP-PA1 (immuno potentiator from P. agglomerans, former name: LPSp). The IP-PA1 is considered to be useful in various fields such as health food (to prevent and improve metabolic syndromes), skincare products (to maintain healthy skin, to improve atopic dermatitis, and to resist aging), and as active ingredients in feeds for stockbreeding and aquaculture (to act as a defense against infection). In this manuscript, we discuss the significance of activation of macrophages through oral or intradermal administration, the discovery of IP-PA1 as a macrophage-activating substance, the chemical structure of IP-PA1, the use of IP-PA1 to improve various disorders, the mechanism of action, and the possibility of application of IP-PA1 to various fields. PMID- 17270713 TI - Novel partial nitritation treatment for anaerobic digestion liquor of swine wastewater using swim-bed technology. AB - A swim-bed reactor using the biofringe acryl-fiber biomass carrier was used for partial nitritation treatment for anaerobic digestion liquor of swine wastewater. The sludge in the reactor demonstrated excellent settling properties, and the sludge volumetric index (SVI) was always about 50 ml g(-1). The mixed liquor suspended solids (MLSS) concentration was maintained above 10,000 mg l(-1) with a maximum of 16,800 mg l(-1). Satisfactory and stable partial nitritation was obtained at a nitrogen loading rate (NLR) of 1.9 kg-N m(-3) d(-1) without any operational control. Only a little nitrate was produced almost during the whole operational period and the nitrite to total oxidized nitrogen ratio (NO(2) N/(NO(2)-N+NO(3)-N)) was always above 95%. In addition, the influence of temperature on partial nitritation efficiencies was also investigated and non controlled efficiencies were maintained stably between 15 degrees C and 30 degrees C at an NLR of 1.9 kg-N m(-3) d(-1), but suddenly deteriorated when the temperature fell below 15 degrees C. Nitrite oxidizing bacteria were inhibited by free ammonia and free nitric acid, which prevented the conversion of nitrite to nitrate and the inhibition due to free nitric acid weaken with a decrease in temperature. It was apparent that these phenomena were crucial to the control of partial nitritation treatment. PMID- 17270714 TI - Molecular cloning, identification and characterization of 2-methyl-3 hydroxypyridine-5-carboxylic-acid-dioxygenase-coding gene from the nitrogen fixing symbiotic bacterium Mesorhizobium loti. AB - The gene (mlr6788) of a nitrogen-fixing symbiotic bacterium Mesorhizobium loti MAFF303099 has been identified as a gene coding for 2-methyl-3-hydroxypyridine-5 carboxylic acid dioxygenase (MHPCO), the seventh enzyme in degradation pathway I for pyridoxine, a free form of vitamin B(6). The gene was cloned and overexpressed in Escherichia coli cells co-transformed with chaperonin genes. The homogeneous recombinant enzyme showed similar enzymatic properties to the enzyme from Pseudomonas sp. MA-1. MHPCO was essential for the assimilation of pyridoxine in M. loti, but not for its growth in a nutrient-rich medium. From the infection experiment of a symbiotic plant Lotus japonicus with an M. loti mlr6788 gene disruptant, MHPCO was demonstrated to be dispensable for at least nodule formation on roots of seedlings in symbiosis. PMID- 17270715 TI - Design of carrier tRNAs and selection of four-base codons for efficient incorporation of various nonnatural amino acids into proteins in Spodoptera frugiperda 21 (Sf21) insect cell-free translation system. AB - Spodoptera frugiperda 21 (Sf21) insect cell-free protein synthesizing system was expanded to include nonnatural amino acids. Orthogonal tRNAs that work as carriers of nonnatural amino acids in the insect system were explored. Four-base codons for assigning the positions of nonnatural amino acids were also selected. Mutated streptavidin mRNAs that contained different four-base codons were prepared and added to the insect cell-free system in the presence of various tRNAs possessing the corresponding four-base anticodons. The tRNAs were chemically aminoacylated with various types of nonnatural amino acids to examine their incorporation efficiencies. Using p-nitrophenylalanine as the nonnatural amino acid and streptavidin as the target protein, tRNA sequences and the types of four-base codons were optimized to maximize the yield of the nonnatural mutant and to minimize production of full-length proteins that do not contain the nonnatural amino acid. Among the tRNA sequences taken from a variety of tRNAs of nonstandard structures, the tRNA derived from Methanosarcina acetivorans tRNA(Pyl) was the most efficient and orthogonal tRNA. Of the CGGN-type four-base codons, CGGA and CGGG were the most efficient ones for assigning the positions of nonnatural amino acids. p-Nitrophenylalanine and 2-naphthylalanine were efficiently incorporated as in the case of Escherichia coli and rabbit reticulocyte cell-free systems. Much less efficient incorporation was observed, however, for other nonnatural amino acids, indicating that the insect system is less tolerant to the structural diversity of amino acids than the E. coli cell free system. PMID- 17270717 TI - Extension of Einstein's viscosity equation to that for concentrated dispersions of solutes and particles. AB - A viscosity equation for concentrated solutions or suspensions is derived as an extension of Einstein's hydrodynamic viscosity theory for dilute dispersions of spherical particles. The derivation of the equation is based on the calculation of dissipation of mechanical energy into heat in the dispersion, subtracting the energy dissipation in the portion of solutes or particles. The viscosity equation derived thus was well fitted to the viscosity-concentration relationship of the concentrated aqueous solutions of glucose and sucrose. For the suspensions of bakers' yeast, the concentration dependency of viscosity was expressed well with some modification for the flow pattern around suspended particles. It is suggested that these viscosity equations can be widely applied to both diluted and concentrated dispersions of various solutes and particles. PMID- 17270716 TI - Transport of human immunoglobulin G and Fc-fusion proteins to chicken egg yolk. AB - We examined the transport of human immunoglobulin G (IgG) subclasses and fusion proteins with the Fc region of human IgG to the egg yolk, after the proteins were injected into a vein of hens. Human IgGs were efficiently transported and accumulated into the yolk, whereas the proteins were not detected in the egg white. Among human IgG subclasses, IgG2 was transported most efficiently. Fc fusion proteins injected were also transported into the yolk. A fusion protein with the Fc region derived from human IgG2 was more efficiently transported into the yolk than the counterpart fusion with the Fc region from human IgG1. This study shows that the recovery of recombinant antibodies and Fc-fusion proteins from the yolk is an effective method in transgenic chicken bioreactors. PMID- 17270718 TI - Fermentative production of (R)-(-)-3-hydroxybutyrate using 3-hydroxybutyrate dehydrogenase null mutant of Ralstonia eutropha and recombinant Escherichia coli. AB - Two systems, one using an (R)-(-)-3-hydroxybutyrate dehydrogenase (BDH) null mutant of Ralstonia eutropha and the other using a recombinant Escherichia coli strain containing a synthetic poly[(R)-(-)-3-hydroxybutyrate] (PHB) operon and an extracellular PHB depolymerase gene, were used for the fermentative production of (R)-(-)-3-hydroxybutyrate (3HB). The concentration of 3HB in the culture supernatant of the mutant R. eutropha system reached about 30 mM after 5 d under anaerobic conditions, although it was about 4-10 mM under aerobic conditions. On the other hand, the 3HB concentration in the culture supernatant of the recombinant E. coli system reached about 70 mM after 4 d, indicating that about 70% of the glucose added was converted to 3HB. PMID- 17270720 TI - Purification, characterization, and gene cloning of glycerol dehydrogenase from Hansenula ofunaensis, and its expression for production of optically active diol. AB - Optically active alcohol is an important building block as a versatile chiral synthon for the asymmetric synthesis of pharmaceuticals and agrochemicals. We purified and characterized glycerol dehydrogenase from Hansenula ofunaensis and prepared optically active 1,2-octanediol using a recombinant Escherichia coli harboring the glycerol dehydrogenase gene. The deduced amino acid sequence was investigated for identities with those of other alcohol dehydrogenases in the NCBI databank. The identification of the unknown product of a resting-cell reaction was performed by GC-MS. In the deduced amino acid sequence composed of 376 residues, the NAD(H) binding pattern and cysteine residues that correspond to the cysteine ligands at the zinc atom were conserved as they are in alcohol dehydrogenases from other origins. Glycerol dehydrogenase from Hansenula polymorpha DL-1 (Pichia angusta, DDBJ/EMBL/GenBank accession no. BAD32688) had the highest identity to our enzyme, showing 73% identity. Our glycerol dehydrogenase catalyzed the NAD(+)-dependent oxidation of long-chain secondary alcohols such as 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, and 1,2 octanediol. Activities toward 2,4-pentanediol and 2,5-hexanediol were hardly detected. From these results, it was confirmed that our enzyme requires two hydroxyl groups on adjacent carbon atoms for oxidation. 2,3-Pentanedione, 2,3 hexanedione, and 3,4-hexanedione were significantly reduced. The transformants oxidized only (R)-1,2-octanediol in 50 mM racemate (R:S=52:48), and produced (S) 1,2-octanediol (24 mM, <99.9% e.e.) after 24 h of incubation. The reaction product was suggested to be 1-hydroxy-2-octanone by GC-MS, which showed secondary hydroxyl groups oxidized. Glycerol dehydrogenase from H. ofunaensis could be useful for the production of long-chain optically active secondary alcohols. PMID- 17270719 TI - Microbial diversity of mesophilic methanogenic consortium that can degrade long chain fatty acids in chemostat cultivation. AB - We established a chemostat cultivation method for a mesophilic methanogenic consortium that could degrade long-chain fatty acids (LCFA) using a completely stirred tank reactor (CSTR) fed with synthetic wastewater containing oleic and palmitic acids as the carbon and energy sources. The critical dilution rate of the chemostat, in which most of the introduced LCFA were decomposed and mineralized, was 0.4 d(-1). The microbial community under steady-state condition at this dilution rate was analyzed by 16S rRNA gene sequencing. We detected the following major groups of methanogens within the archaeal community: the aceticlastic genera Methanosaeta and Methanosarcina and the hydrogenotrophic genus Methanospirillum. We also detected organisms that were closely related to fatty-acid oxidizing bacteria affiliated with the family Syntrophomonadaceae. However, bacteria belonging to the phyla Bacteroidetes and Spirochaetes, which are phylogenetically distant from known fatty-acid oxidizing bacteria, apparently predominated in the population, indicating that they play important roles in LCFA degradation within the chemostat. PMID- 17270722 TI - Supplementation effect of ectoine on thermostability of phytase. AB - In this study, we elucidated the supplementation effect of compatible solutes on the thermostability of phytase, designated as PHYA II, which was encoded by the phytase gene phyA I (GeneBank AY013315) from Aspergillus ficuum As3.324 and expressed in Pichia pastoris GS115. When PHYA II in acetate buffer was heated at 90 degrees C for 15 min, more than 80% of the residual activity was retained by adding the cyclic amino acid ectoine, a representative compatible solute. Furthermore, the presence of ectoine led to an increase in the relative hydrolytic rate of sodium phytate by 15.7% with heating at 80 degrees C for 15 min. Among the compatible solutes examined, ectoine was confirmed to be the most efficient thermoprotectant for PHYA II. PMID- 17270721 TI - Streptomyces-derived induction system for gene expression in cultured plant cells. AB - We have constructed an induction system for plant gene expression using an operator/repressor gene pair of Streptomyces virginiae. In this system, the repressor protein BarA dissociates from the operator sequence BARE in the presence of an inducer virginiae butanolide (VB), resulting in the induction of the transcription of the operator's downstream genes required for virginiamycin biosynthesis [Kinoshita et al., J. Bacteriol., 179, 6986-6993 ((1997))]. Two vectors were constructed: one was an effector plasmid, in which BarA was driven by plant promoters, and the other was a reporter plasmid, in which the BARE sequence was incorporated into the cauliflower mosaic virus 35S promoter to express the Escherichia coli beta-glucuronidase gene (GUS). An electroporation mediated gene expression assay with cultured tobacco cells showed that GUS expression from the reporter plasmid was repressed upon coexpression with the effector plasmid and that the repression was relieved by VB. The result of electroporation to insert the reporter plasmid with various numbers and positions of BAREs into tobacco cells that had been transformed with the effector plasmid showed that the GUS induction by derepression increases with the number of BAREs and with BAREs downstream rather than upstream of the TATA box. Double transformants with the effector and reporter plasmids showed 30-fold induction with VB. The induction appeared within 8 h after VB addition, maximum induction being observed with 1 microM VB. PMID- 17270723 TI - Expression of Aspergillus oryzae phytase gene in Aspergillus oryzae RIB40 niaD( ). AB - Aspergillus oryzae RIB40 niaD(-) was transformed using a plasmid constructed with the A. oryzae phytase gene and pNAN8142 vector. The culture broth of the transformant, which was grown in a medium containing starch as a carbon source and polyvinylpyrrolidone showed phytase activity of a maximum of 2.0 units ml(-1) at 37 degrees C, pH 5.5. PMID- 17270724 TI - Comparison of transcriptional responses to osmotic stresses induced by NaCl and sorbitol additions in Saccharomyces cerevisiae using DNA microarray. AB - Transcriptional responses of laboratory and brewing strains of Saccharomyces cerevisiae to osmotic stresses induced by adding either NaCl or sorbitol to their cultures were compared by clustering DNA microarray data. Our results suggest that the difference in the transcriptional responses of the two strains between NaCl and sorbitol additions is small when the dynamics of the total change in gene expression are similar. PMID- 17270725 TI - High-throughput genotyping of filamentous fungus Aspergillus oryzae based on colony direct polymerase chain reaction. AB - High-throughput genotyping of Aspergillus oryzae was achieved using an FTA card for the extraction of a genomic DNA template for polymerase chain reaction from a fungal colony growing on an agar plate. This method was then applied to detect other fungal species from agar slants and food materials. This method offers a convenient tool for the genotyping of filamentous fungi without using an organic solvent or specialized equipment. PMID- 17270727 TI - Reversal of misfolding: prion disease behavioral and physiological impairments recover following postnatal neuronal deletion of the PrP gene. AB - The prionoses are fatal neurodegenerative diseases caused by a pathogenic protein, PrP scrapie, that derives from misfolding of a normal form, PrP(c). These diseases progress through stages. A new study by Mallucci et al. in this issue of Neuron shows that prion disease may be reversed in mice by selective removal of the gene in neurons after early physiological, cognitive, and pathological features have developed. PMID- 17270726 TI - Single cell-based analysis of torenia petal pigments by a combination of ArF excimer laser micro sampling and nano-high performance liquid chromatography (HPLC)-mass spectrometry. AB - The molecular constituents of the petal pigments of the Torenia plant (Torenia hybrida) were analyzed on a single-cell basis by a combination of newly developed laser-microsampling and nano-flow liquid chromatography-electro spray ionization mass spectrometry (LC-ESIMS) techniques. Our method should provide a facile method for obtaining precise metabolic profiles of each cell in a single plant tissue. PMID- 17270728 TI - Picking up the pieces: the roles of functional remnants of calpain-mediated proteolysis. AB - Calpain-mediated cleavage of neuronal targets has long been associated with excitotoxicity and synaptic plasticity. In this issue of Neuron, two papers by Xu et al. and Abe and Takeichi explore the respective roles of mGluR1alpha cleavage in excitotoxicity and beta-catenin cleavage in transcriptional control. Together, these papers show the functional importance of fragments of calpain-mediated cleavage. PMID- 17270729 TI - Cortical songs revisited: a lesson in statistics. AB - Recordings from single neurons in the cortex have revealed precisely repeating patterns of synaptic events. These repeats are known as cortical "motifs" and have been suggested to reflect the precise replay of spatiotemporal firing sequences ("synfire" chains). In this issue of Neuron, Mokeichev et al. use compelling statistical analysis to show that, rather than being evidence of deterministic synfire chains, such cortical motifs are bound to appear by chance due to the natural dynamics of voltage fluctuations in neurons. PMID- 17270730 TI - Behavioral flexibility and the frontal lobe. AB - Brain areas in the frontal lobe have been implicated in behavioral flexibility and control. The study by Johnston et al. in this issue of Neuron provides novel insights into the roles of the prefrontal and anterior cingulate cortices in controlling behavior. PMID- 17270731 TI - Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice. AB - Currently, no treatment can prevent the cognitive and motor decline associated with widespread neurodegeneration in prion disease. However, we previously showed that targeting endogenous neuronal prion protein (PrP(C)) (the precursor of its disease-associated isoform, PrP(Sc)) in mice with early prion infection reversed spongiform change and prevented clinical symptoms and neuronal loss. We now show that cognitive and behavioral deficits and impaired neurophysiological function accompany early hippocampal spongiform pathology. Remarkably, these behavioral and synaptic impairments recover when neuronal PrP(C) is depleted, in parallel with reversal of spongiosis. Thus, early functional impairments precede neuronal loss in prion disease and can be rescued. Further, they occur before extensive PrP(Sc) deposits accumulate and recover rapidly after PrP(C) depletion, supporting the concept that they are caused by a transient neurotoxic species, distinct from aggregated PrP(Sc). These data suggest that early intervention in human prion disease may lead to recovery of cognitive and behavioral symptoms. PMID- 17270732 TI - Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. AB - Filamentous tau inclusions are hallmarks of Alzheimer's disease (AD) and related tauopathies, but earlier pathologies may herald disease onset. To investigate this, we studied wild-type and P301S mutant human tau transgenic (Tg) mice. Filamentous tau lesions developed in P301S Tg mice at 6 months of age, and progressively accumulated in association with striking neuron loss as well as hippocampal and entorhinal cortical atrophy by 9-12 months of age. Remarkably, hippocampal synapse loss and impaired synaptic function were detected in 3 month old P301S Tg mice before fibrillary tau tangles emerged. Prominent microglial activation also preceded tangle formation. Importantly, immunosuppression of young P301S Tg mice with FK506 attenuated tau pathology and increased lifespan, thereby linking neuroinflammation to early progression of tauopathies. Thus, hippocampal synaptic pathology and microgliosis may be the earliest manifestations of neurodegenerative tauopathies, and abrogation of tau-induced microglial activation could retard progression of these disorders. PMID- 17270733 TI - Mechanisms of odor receptor gene choice in Drosophila. AB - A remarkable problem in neurobiology is how olfactory receptor neurons (ORNs) select, from among a large odor receptor repertoire, which receptors to express. We use computational algorithms and mutational analysis to define positive and negative regulatory elements that are required for selection of odor receptor (Or) genes in the proper olfactory organ of Drosophila, and we identify an element that is essential for selection in one ORN class. Two odor receptors are coexpressed by virtue of the alternative splicing of a single gene, and we identify dicistronic mRNAs that each encode two receptors. Systematic analysis reveals no evidence for negative feedback regulation, but provides evidence that the choices made by neighboring ORNs of a sensillum are coordinated via the asymmetric segregation of regulatory factors from a common progenitor. We show that receptor gene choice in Drosophila also depends on a combinatorial code of transcription factors to generate the receptor-to-neuron map. PMID- 17270735 TI - NMDA-receptor activation induces calpain-mediated beta-catenin cleavages for triggering gene expression. AB - The canonical Wnt-beta-catenin signaling pathway is important for a variety of developmental phenomena as well as for carcinogenesis. Here, we show that, in hippocampal neurons, NMDA-receptor-dependent activation of calpain induced the cleavage of beta-catenin at the N terminus, generating stable, truncated forms. These beta-catenin fragments accumulated in the nucleus and induced Tcf/Lef dependent gene transcription. We identified Fosl1, one of the immediate-early genes, as a target of this signaling pathway. In addition, exploratory behavior by mice resulted in a similar cleavage of beta-catenin, as well as activation of the Tcf signaling pathway, in hippocampal neurons. Both beta-catenin cleavage and Tcf-dependent gene transcription were suppressed by calpain inhibitors. These findings reveal another pathway for beta-catenin-dependent signaling, in addition to the canonical Wnt-beta-catenin pathway, and suggest that this other pathway could play an important role in activity-dependent gene expression. PMID- 17270734 TI - Hair bundles are specialized for ATP delivery via creatine kinase. AB - When stimulated strongly, a hair cell's mechanically sensitive hair bundle may consume ATP too rapidly for replenishment by diffusion. To provide a broad view of the bundle's protein complement, including those proteins participating in energy metabolism, we used shotgun mass spectrometry methods to identify proteins of purified chicken vestibular bundles. In addition to cytoskeletal proteins, proteins involved in Ca(2+) regulation, and stress-response proteins, many of the most abundant bundle proteins that were identified by mass spectrometry were involved in ATP synthesis. After beta-actin, the cytosolic brain isoform of creatine kinase was the next most abundant bundle protein; at approximately 0.5 mM, creatine kinase is capable of maintaining high ATP levels despite 1 mM/s ATP consumption by the plasma-membrane Ca(2+)-ATPase. Consistent with this critical role in hair bundle function, the creatine kinase circuit is essential for high sensitivity hearing as demonstrated by hearing loss in creatine kinase knockout mice. PMID- 17270736 TI - Calpain-mediated mGluR1alpha truncation: a key step in excitotoxicity. AB - Excitotoxicity mediated by glutamate receptors plays crucial roles in ischemia and other neurodegenerative diseases. Whereas overactivation of ionotropic glutamate receptors is neurotoxic, the role of metabotropic glutamate receptors (mGluRs), and especially mGluR1, remains equivocal. Here we report that activation of NMDA receptors results in calpain-mediated truncation of the C terminal domain of mGluR1alpha at Ser(936). The truncated mGluR1alpha maintains its ability to increase cytosolic calcium while it no longer activates the neuroprotective PI(3)K-Akt signaling pathways. Full-length and truncated forms of mGluR1alpha play distinct roles in excitotoxic neuronal degeneration in cultured neurons. A fusion peptide derived from the calpain cleavage site of mGluR1alpha efficiently blocks NMDA-induced truncation of mGluR1alpha in primary neuronal cultures and exhibits neuroprotection against excitotoxicity both in vitro and in vivo. These findings shed light on the relationship between NMDA and mGluR1alpha and indicate the existence of a positive feedback regulation in excitotoxicity involving calpain and mGluR1alpha. PMID- 17270737 TI - Stochastic emergence of repeating cortical motifs in spontaneous membrane potential fluctuations in vivo. AB - It was recently discovered that subthreshold membrane potential fluctuations of cortical neurons can precisely repeat during spontaneous activity, seconds to minutes apart, both in brain slices and in anesthetized animals. These repeats, also called cortical motifs, were suggested to reflect a replay of sequential neuronal firing patterns. We searched for motifs in spontaneous activity, recorded from the rat barrel cortex and from the cat striate cortex of anesthetized animals, and found numerous repeating patterns of high similarity and repetition rates. To test their significance, various statistics were compared between physiological data and three different types of stochastic surrogate data that preserve dynamical characteristics of the recorded data. We found no evidence for the existence of deterministically generated cortical motifs. Rather, the stochastic properties of cortical motifs suggest that they appear by chance, as a result of the constraints imposed by the coarse dynamics of subthreshold ongoing activity. PMID- 17270738 TI - Timing in the absence of clocks: encoding time in neural network states. AB - Decisions based on the timing of sensory events are fundamental to sensory processing. However, the mechanisms by which the brain measures time over ranges of milliseconds to seconds remain unclear. The dominant model of temporal processing proposes that an oscillator emits events that are integrated to provide a linear metric of time. We examine an alternate model in which cortical networks are inherently able to tell time as a result of time-dependent changes in network state. Using computer simulations we show that within this framework, there is no linear metric of time, and that a given interval is encoded in the context of preceding events. Human psychophysical studies were used to examine the predictions of the model. Our results provide theoretical and experimental evidence that, for short intervals, there is no linear metric of time, and that time may be encoded in the high-dimensional state of local neural networks. PMID- 17270739 TI - Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. AB - Hallucinogens, including mescaline, psilocybin, and lysergic acid diethylamide (LSD), profoundly affect perception, cognition, and mood. All known drugs of this class are 5-HT(2A) receptor (2AR) agonists, yet closely related 2AR agonists such as lisuride lack comparable psychoactive properties. Why only certain 2AR agonists are hallucinogens and which neural circuits mediate their effects are poorly understood. By genetically expressing 2AR only in cortex, we show that 2AR regulated pathways on cortical neurons are sufficient to mediate the signaling pattern and behavioral response to hallucinogens. Hallucinogenic and nonhallucinogenic 2AR agonists both regulate signaling in the same 2AR-expressing cortical neurons. However, the signaling and behavioral responses to the hallucinogens are distinct. While lisuride and LSD both act at 2AR expressed by cortex neurons to regulate phospholipase C, LSD responses also involve pertussis toxin-sensitive heterotrimeric G(i/o) proteins and Src. These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens. PMID- 17270740 TI - Top-down control-signal dynamics in anterior cingulate and prefrontal cortex neurons following task switching. AB - The prefrontal cortex (PFC) and anterior cingulate cortex (ACC) have both been implicated in cognitive control, but their relative roles remain unclear. Here we recorded the activity of single neurons in both areas while monkeys performed a task that required them to switch between trials in which they had to look toward a flashed stimulus (prosaccades) and trials in which they had to look away from the stimulus (antisaccades). We found that ACC neurons had a higher level of task selectivity than PFC neurons during the preparatory period on trials immediately following a task switch. In ACC neurons, task selectivity was strongest after the task switch and declined throughout the task block, whereas task selectivity remained constant in the PFC. These results demonstrate that the ACC is recruited when cognitive demands increase and suggest a role for both areas in task maintenance and the implementation of top-down control. PMID- 17270741 TI - Autofluorescence lifetime measurement on oral carcinogenesis. AB - Normal and cancerous tissues have distinct autofluorescence lifetime because of their biophysical and biochemical differences. Protoporphyrin IX (PplX) is a useful fluorophore, which generally accumulates more in cancerous cells than in normal cells due to heme synthesis pathway, is often employed in photodynamic detection and therapy. Under 410nm excitation, the main emission peak of PplX is at 630nm. Autofluorescence lifetime at 630nm emission would be elongated if PplX gathered more in cells. In this study, we tried to find if there exist significant differences of autofluorescence lifetime at 630nm (under 410nm excitation) between normal and cancerous tissues for in vivo measurement. The result shows that normal tissues in general have shorter lifetime (about 2.8 approximately 3.5 ns) than that of abnormal tissues. The measured data suggest that lifetime would get longer in accordance with the degree of carcinogenesis. For cancer tissues, the average autofluorescence lifetime was extended to be about 10ns. Furthermore, the efficiency of treatment could also be defined refer to the time-series of lifetime decline. PMID- 17270742 TI - Continuous wave Doppler methods to dialysis access monitoring. AB - Dialysis access failure is the major cause of morbidity among patients undergoing hemodialysis. Reduced blood flow reveals access malfunction. This work discusses two methods based on directional continuous wave Doppler system to evaluate the access blood flow. By changing the dialysis blood pump flow rate, the variable flow Doppler method measures the access blood flow. Software was developed to make feasible its application during clinical routine. A second method proposes the spectral broadening index (SBI) to characterize the access performance. Preliminary results show that a SBI above 1.9 denotes poor blood flow (less than 600ml/min. Sensibility=80%. Specificity=83%). According to the National Kidney Foundation, patients whose access flow is inferior to 600 ml/min should be referred for fistulogram. The second method is easier to be applied in dialysis sessions. PMID- 17270743 TI - Water vapour partial pressure control in neonatal incubator using prevision by multiple models. AB - One of the phenomena that affect the water loss in newborn infants is the humidity. The evaporation is determined by the vapour partial pressure. As well as temperature control, the reduction of the vapour partial pressure oscillations has an important role in the establishment of thermal comfort for newborn infants in incubators. This work presents an algorithm based on multiple models to water vapour partial pressure control. The tests have been made in an acrylic prototype simulating a commercial incubator. The results shows that the implemented control algorithm presents oscillations minor to +/-0.08 kPa. PMID- 17270744 TI - Characteristic properties of implantable Ag/AgCl- and Pt-electrodes. AB - Traditional potential measurement from the surface of skin, e.g. ECG, has the shortcoming of motion artifact and possible power-line interference. Further problems in the measurement can occur from the time and place dependency of the measurement. All of these problems can be avoided by using an implantable measurement device. With an implantable device one can access many such quantities in man where there is no access with traditional measurement setups. This research paper deals with noise measurements of implantable electrodes in saline. Electrode characteristics are also investigated. More specific electrode electrolyte interface capacitance and resistance are determined from some of the electrodes studied. PMID- 17270745 TI - Development stress monitoring system based on personal digital assistant (PDA). AB - We have developed nonintrusive type stress monitoring system based on the PDA (Personal Digital Assistance). This system separated sensing part of the physiological signal and estimating part of the stress states. First, sensing part consists of four electrodes such as one PPG electrode, two EDA electrodes and one SKT electrode. Sensing part was able to measuring heart rate, skin temperature variation, and electrodermal activity, all of which can be acquired without discomfort from finger. Second, estimating part was developed and verified for physiological signal database that was obtained from multiple subjects by presenting stress stimuli that were elaborated to effectively induce stress. This system is a useful measure of human stress in portabel device as PDA and smart phone. PMID- 17270746 TI - Measuring bioimpedance in the human uterine cervix: towards early detection of preterm labor. AB - We have created a bioimpedance probe designed to detect subtle changes in human cervical tissue composition in vivo, and thereby detect the onset of cervical remodeling in a noninvasive manner sooner than existing clinical methods allow. Our cervical bioimpedance measurement device, which can be used during a routine pelvic examination, is composed of a contoured probe with disposable tip and, within the probe's handle, a bioimpedance sensor equipped with an integrated chip capable of generating sinusoidal voltage of varying frequencies. A constant force spring assures consistent measurements through a range of contact forces applied. An activation switch allows the operator to control the application of current. The sensor can be synchronized with a computer data storage and analysis system, which interfaces with the device. With the probe placed in contact with a collagen gels of varying concentration, the relationship between measured bioimpedance and collagen concentration is verified to be positive exponential (R/sup 2/=0.94) and repeatability in saline solution showed that measurements varied by less than +/-10% over 20 trials. Finally, a variety of user-applied forces showed that impedance values plateau when forces exceed 1N. PMID- 17270747 TI - An ECG electrode-mounted heart rate, respiratory rhythm, posture and behavior recording system. AB - R-R interval, respiration rhythm, posture and behavior recording system has been developed for monitoring a patient's cardiovascular regulatory system in daily life. The recording system consists of three ECG chest electrodes, a variable gain instrumentation amplifier, a dual axis accelerometer, a low power 8-bit single-chip microcomputer and a 1024 KB EEPROM. The complete system is mounted on the chest electrodes. R-R interval and respiration rhythm are calculated by the R waves detected from the ECG. Posture and behavior such as walking and running are detected from the body movements recorded by the accelerometer. The detected data are stored by the EEPROM and, after recording, are downloaded to a desktop computer for analysis. PMID- 17270748 TI - The electrically non-contacting ECG measurement on the toilet seat using the capacitively-coupled insulated electrodes. AB - The studies of ECG measurement on the toilet seat have been performed specifically for the ubiquitous health care. Instead of the mainly used dry electrodes having several problems such as the electrical safety or the environmental stability, we used the capacitively-coupled insulated electrodes, which were composed of the Cu plate and the PTFE film for the measurement. The biosignal sensed with the insulated electrodes was measured through the ultra high input impedance system including OPA111 having the common mode impedance of 10/sup 14/ Omega ft. As the result of measuring the signal, with the electrical ground on the neck or the hand, the R-peaks were detected very positively. However, without the electrical ground on the body, we could detect the heartbeat signal, a land of the motion artifacts by the variation of the blood vessel volume. It seems that this heartbeat signal can be also used as the important parameter like the R-peaks for the HRV (heart rate variability) analysis. In addition, it is thought that, without the directly electrical ground, the R-peak detection will be possible by the improvement of the SNR with the active common canceling system. PMID- 17270749 TI - Ambulatory instrumentation suitable for long-term monitoring of cattle health. AB - The benefits of real-time health diagnoses of cattle are potentially tremendous. Early detection of transmissible disease, whether from natural or terrorist events, could help to avoid huge financial losses in the agriculture industry while also improving meat quality. This work discusses physiological and behavioral parameters relevant to cattle state-of-health assessment. These parameters, along with a potentially harsh monitoring environment, drive a set of design considerations that must be addressed when building systems to acquire long-term, real-time measurements in the field. A prototype system is presented that supports the measurement of suitable physiologic parameters and begins to address the design constraints for continuous state-of-health determination in free-roaming cattle. PMID- 17270750 TI - The ECG measurement in the bathtub using the insulated electrodes. AB - The ECG recording in the bathtub was studied using insulated electrode. Prior studies of the ECG recording in the bathtub used conductive electrodes having some problems such as the possibility of the electric shock and sensitivity to contamination of the electrode surfaces. The insulated electrodes were made of copper plate coated with PET film. The electrodes were attached on bathtub at both sides of the chest. High-input-impedance amplifier was designed to amplify ECG signal sensed by insulated electrodes of high impedance. The recorded signals in this study were noisier than those recorded with conventional conductive electrodes. But the R peaks in the recorded signals were large enough to be auto detected. Further study will improve SNR by reducing of power line noise and common-mode noise. PMID- 17270751 TI - Variable frequency bioimpedance instrumentation. AB - The design of instrumentation used to measure the bioimpedance of skin or tissue is presented. An inexpensive, component level approach, appropriate for use by researchers rather that commercial applications, is emphasized. The design and implementation process is thoroughly explained and design tradeoffs are discussed with relation to various applications. A validation of the implementation in hardware is presented and an example application to skin impedance topography is considered. PMID- 17270752 TI - Effect of ultrasound exposure on surfactant microbubbles. AB - In this study, the effect of ultrasound exposure on number and scattering intensity from microbubbles in blood vessel model is noticed. Experimentally, microbubbles are produced using surfactant solution, and the measurement of number and scattering intensity of microbubbles are performed. Furthermore, theoretical calculation of scattering intensity from microbubbles in blood vessel model is performed to compare with experimental results. From the comparison of calculation and experiment, the effectiveness of constructed calculation model is confirmed. PMID- 17270753 TI - Human behavior and egocentric spatial perception contingent with gravity cue. AB - Gravity modifies us without our knowing it. Possible functional disabilities of eye, head and body movements were investigated under 1G and microgravity environments to evaluate the gravity cue for human behavior. The system for visual stability might be explained from the viewpoint of coordination between eye and head under microgravity. It is important to ascertain the significance of gravity in the maintenance of human visual stability. Coordination of eye position and head motion behavior by neck muscle discharge was examined in the mission SL-J, as well as a subjective evaluation of visual stability during spaceflight. There are a lot of discussion about human behavior contingent with gravity which has not been discussed ever. PMID- 17270754 TI - Effects of virtual body motion on visually-induced motion sickness. AB - To reduce possibilities of visually-induced motion sickness caused by animations, video games and movies, we need to develop an evaluation method of visually induced motion sickness. Our previous results have shown that virtual roll motion had the most effective for producing the sickness. In the present study, we focused on the effectivity of image types, such as random dots and ordinary scene, and also the effectivity of virtual rotation speed on the sickness. In the first experiment, we confirmed our former results that virtual roll motion produced the highest score relating motion sickness, regardless of image types. In the second experiment, virtual rotation speed of 30 to 60 deg/s gave the highest scores regardless of the rotation types, yawing, pitching and rolling. We concluded that moving images simulating nonreciprocating rolling has robust effects on the sickness. Moreover, we speculated that the effect of rotation speed is determined by inconsistency of visual and nonvisual information, but not by retinal image speed. PMID- 17270755 TI - Time-varying behavior of motion vectors in vection-induced images in relation to autonomic regulation. AB - Virtual reality (VR) is a promising technology in biomedical engineering, but at the same time enlarges another problem called cybersickness. Aiming at suppression of cybersicknes, we are investigating the influences of vection induced images on the autonomic regulation quantitatively. We used the motion vectors to quantify image scenes and measured electrocardiogram, blood pressure, and respiration for evaluating the autonomic regulation. Using the estimated motion vectors, we further synthesized random-dot pattern images to survey which component of the global motion vectors seriously affected the autonomic regulation. The results showed that the zoom component with a specific frequency band (0.1-3.0 Hz) would induce sickness. PMID- 17270756 TI - Quantitative evaluation of the effect of visually-induced motion sickness using causal coherence function between blood pressure and heart rate. AB - To evaluate the effect of visually-induced motion sickness on the human, blood pressure variability (BP) and heart rate variability (HR) of 51 normal subjects watching a 15min-long video image taken by a vibrating handy camera were analyzed. Not only coherence function (K/sup 2/) between BP and HR but also two causal coherence functions: K/sup 2//sub BP-->HR/ from BP to HR and K/sup 2//sub HR-->BP/ from HR to BP were introduced to divide causal linearity of the cardiovascular system regarded as a closed-loop system. K/sup 2/ represents total linearity of the system. K/sup 2//sub BP-->HR/ and K/sup 2//sub HR-->BP/ correspond to the baroreflex system and the mechanical hemodynamics, respectively. The results revealed that K/sup 2//sub BP-->HR/ at the Mayer wave band (around 0.1 Hz) of the subjects prone to motion sickness decreased gradually and was significantly lower than that of the subjects not prone to in later scenes. This result has never been obtained from conventional methods dealing with a cardiovascular system as an open-loop system. PMID- 17270757 TI - Assessment of emotional reaction induced by visual stimulation based on cross correlation between pulse wave transmission time and heart rate in the Mayer wave band. AB - Mayer wave (0.1Hz fluctuation) included in heart rate variability and blood pressure variability appears apparently in the resting state. On the other hand, it can be predicted that a strong emotional reaction may affect the relationship between these variabilities. This prediction suggests that the human emotional reaction can be quantified by the maximum correlation coefficient rho/sub max/ between heart rate and blood pressure whose frequency components are limited to the Mayer wave-band. However, the conventional method of obtaining rho/sub max/ needs a bulky and expensive device for measuring continuous blood pressure. In this study, a smaller and cheaper device for measuring pulse wave transmission time (PTT) has been developed. This work has shown that the PTT can give rho/sub max/ instead of blood pressure and that rho/sub max/ obtained by the PTT may significantly reflect the emotional reaction on the basis of an experiment using nine healthy subjects with nine self-produced devices in which pictures were presented to the subjects to induce their emotional reactions. PMID- 17270758 TI - Influence of attention and predictive visual cue on motion perception and sickness in immersive virtual environment. AB - Relieving motion sickness and enhancing self-motion perception are required for the public application of immersive visual display system. The effects of user attention and predictive visual cue have been experimentally evaluated in this study. A viewpoint moving visual stimulus was applied to eighteen healthy adults. The subjective evaluation presumably suggested that a predictive visual cue enhances self-motion perception and relieves motion sickness at a same time. PMID- 17270759 TI - Biomechanics of cranial dynamics during daily living activities. AB - Motion tracking capabilities of a head-mounted accelerometer apparatus were investigated in conjunction with three-dimensional motion analysis techniques during activities of daily living. In this report, measures between systems are compared for jogging, toe-touching, and start-from-rest tasks. Good fidelity was found for most measures between systems; some phase shifts and amplitude discrepancies were observed, and attributed to transducer orientation and system asynchrony. This preliminary work demonstrates the potential benefits of hybrid motion analysis systems. PMID- 17270760 TI - MEMS shear stress sensors for cardiovascular diagnostics. AB - Coronary artery disease is the leading cause of morbidity and mortality in the industrialized nations. Both biochemical and biomechanical stimuli modulate the pathogenesis of coronary artery diseases. Shear stress acting on the lumen of blood vessels intimately modulates the biological activities of vascular endothelial cells (ECs). We hereby develop microelectro mechanical system (MEMS) based sensors at the dimension comparable to a single EC to monitor realtime shear stress in fluidic channel. Our goal is to fabricate sensors for ex vivo or in vivo shear stress measurement at Reynolds number commonly encountered in human circulation. The MEMS sensors were designed based on the previously described heat transfer principles. The polysilicon was doped with phosphorous to render the sensing element a high resistivity at 2.5 KOmega. The development of backside wire bonding enabled the application for the vascular geometry. The small dimension (80x2 mum) and the gain amplitude at 71 KHz offered an entry point to measure shear stress with high spatial and temporal resolution. PMID- 17270761 TI - Analysis of surface plasmon resonance data using a partial least square regression method for glucose concentration estimation. AB - A wavelength-based surface plasmon resonance (SPR) technique has been used for the measurement of glucose concentration in aqueous solution. Adoption of partial least square (PLS) regression modeling on SPR data with the proposed simple data pretreatment method provides a much better model than using traditional minima hunting with curve-fitting method. PLS gives the prediction error of 27.63 mg/dL with using unscrambler PLS-toolbox while the traditional method gives an error of 72.15 mg/dL. PMID- 17270762 TI - The design and fabrication of two-dimension multi-electrodes array chip and system. AB - We reported a design and fabrication by using microelectro-mechanical-systems (MEMS) processes of a planar 64-channel multielectrode-array (MEA) chip for recording and/or stimulating cells or tissue slice. The 8 multichannels recording system was designed to verify the bioelectronic signal detected from the MEA chip. The active electrode area can be 20 mumx20 mum or 40 mumx40 mum and with 200 mum or 140 mum space between electrodes, and the metal circuit layout is protected by thin silicone dioxide. Then, the DC measurement to prove this MEA chip device can detect bio-electronic signal normally and immersing the MEA chip in the physiological saline buffer solution to verify that the performance in the AC condition. PMID- 17270763 TI - Pressure sensors for in vivo measurements on spinal growth plates. AB - A new transducer system has been developed for in vivo measurement of pressure on spinal growth plates. A model has been previously proposed for correcting spinal deformities with a staple-like implant, and this sensor will be used in vivo to quantify the pressure that alters growth in this new model of deformity and treatment. The pressure sensor die was 0.65 mm/sup 3/ and the overall packaged sensor size was 1.5 mmx4 mmx0.9 mm. The completed sensors were fully characterized by hydrostatic and compression tests, and performed linearly. The ruggedness and small package size will allow the sensor to be placed bilaterally in the annulus of porcine spinal intervertebral discs to record pressure for up to two weeks. PMID- 17270764 TI - Importance of skin resistance in the reverse iontophoresis-based noninvasive glucose monitoring system. AB - Utilization of the changes in skin resistance during reverse iontophoresis is proposed to detect severe perspiration as well as to correct the glucose estimation. Developed system consists of the amperometric biosensor unit, the electrode unit, a constant current driver circuit and a microcontroller-based control. Performance of the developed system was evaluated by the in-vitro skin model which was specially designed for reverse iontophoresis system. PMID- 17270765 TI - A new position measurement system for micro-measurements in orthopaedics. AB - This paper describes both a legacy position measurement system and a new position measurement system developed for use in making accurate position measurements on the order of 1 mum (micro-measurements) specifically related to the evaluation of orthopaedic implants during simulated use. Commercially available components including an off the shelf position sensor and off the shelf data acquisition hardware are integrated with a signal conditioner designed around off the shelf components, and custom written software in the new measurement system. This new system exhibits marked improvements in cost, accuracy, range and ruggedness over the legacy measurement system used for the same purpose, and has been adopted for the evaluation of orthopaedic implants. PMID- 17270766 TI - Validation of four major algorithms for estimating the instantaneous helical axis with miniature triaxial gyroscope. AB - This work presents an experimental validation study of four major algorithms for estimating the instantaneous helical axis parameters for rigid-body motion. The angular velocity vector was first estimated from landmarks trajectories by four methods and compared to the measured one by a miniature triaxial gyroscope. It was found that the four methods are equivalent, that the estimated angular velocity closely matches the measured one and increasing the number of markers have the effect of smoothing the helical parameters. PMID- 17270767 TI - Quantification of pre-parturition restlessness in crated sows using ultrasonic measurement. AB - This study presents the non-video, noninvasive, automatic, and on-site monitoring system employing ultrasonic transducers to detect the behavior in sows before, during and after parturition. An ultrasonic transmitting/receiving (T/R) circuit of 40kHz is mounted above a conventional parturition bed. The T/R units use ultrasonic time-of-flight (TOP) ranging technology to measure the height of the confined sows at 8 predetermined locations. It is suggested that the system could be applied to automatic prediction of sow parturition, with automatic notification of remote management personnel so human attendance at the birth could reduce rates of sow and piglet mortality. PMID- 17270768 TI - A sEMG-based method for assessing the design of computer mice. AB - Computer users who experience repetitive wrist movements and awkward hand positions are prone to developing upper extremity disorders. Manufacturers have designed various ergonomic mice in response to complaints of pain and discomfort related to computer mouse use. The objective of this work was to validate the use of surface electromyography (sEMG) in assessing the design of nonkeyboard input devices (computer mice). While holding the computer mouse in different grasp positions sEMG of the forearm and hand were recorded during a set of static tasks. The sEMG signal provided information regarding the level of muscle activity and the varied combinations of muscular effort needed to position the hand in a specified posture. A significant decrease in the level of sEMG activity was observed for the pronator muscles when subjects were tested using ergonomic computer mice. The sEMG-based method was validated to be sensitive to the impact of subtle differences in shape/design on the amplitude of the surface EMG data. We also proved a significant effect of hand size and grasp position on the level of muscle activity associated with different mice. PMID- 17270769 TI - Diamond-like carbon coating on micropipettes. AB - Based on glass micropipettes which are widely used in bioengineering and medicine, various microsensor probes could be produced by recent microfabrication techniques. Conductive surfaces of these sensor probes mostly need electrical insulating films coated on them, but it has been difficult to coat a high-quality and strong insulating film on a microacute probe such as a micropipette, especially on its tip. Therefore, we have employed diamond-like carbon (DLC) as an insulating film and developed a DLC coating method based on plasma chemical vapor deposition method. In the deposition apparatus, the cathode is the micropipette itself and the anode is a mesh cylinder with a central focus on the micropipette. In order to prevent the growing films from transformation due to high temperature at the tip, the voltage between the pair of electrodes is impressed intermittently. Raman spectrum and electrical resistivity measured here indicate that the deposited film is DLC and it can be worked well as an insulating film. The DLC coating method could be useful in microprobe fabrications. PMID- 17270770 TI - A new semiconductor lithotripsy sensor. AB - Calibration of lithotripters is important for proper therapeutic treatment of the patients suffering with the presence of the stones in the kidney. Hence, a new semiconductor lithotripsy sensor is developed here to study the optimum performance of the kidney stone disintegrators. The present lithotripsy sensor has four-arm Wheatstone bridge sensor chip having associated electronics of signal conditioning, and amplifier etc. on the chip itself, and is fabricated, by using conventional bipolar IC process, in combination with bulk micromachining process. The starting material used is 5 ohm-cm p-type (100) silicon. The chip size is 3 mm square and the size of anisotropically etched diaphragm is 1.0mmx1.5 mmx20 micron (thickness). The pressure sensitivity is found to be 10 V/mm Hg pressure, with nonlinearity of 0.20% full scale output and thermal stability less than +1.5% over a temperature range of -50 degrees C to 300 degrees C. The smart semiconductor lithotripsy sensor, due to better sensitivity and resolution, is found useful in monitoring of the acoustic intensity level and pressure amplitude (in MPa range) of the shock waves generated by the ESWL. The calibration of the lithotripters is discussed here in detail. PMID- 17270771 TI - Material identification using real and simulated thermal cues. AB - The objective of this study was to develop a thermal display for simulating the thermal cues associated with making contact with materials with different thermal properties. The thermal display was designed based on a semiinfinite body model. The performance of subjects using this display was compared to that with real materials in a material identification experiment. The results indicated that there was no significant difference in material identification when subjects were presented with real or simulated materials. The decreases in skin temperature were also comparable in the two experiments and were related to the contact coefficient of the material palpated, which is consistent with the semiinfinite body model. These findings suggest that thermal feedback in a haptic display can facilitate object recognition when visual cues are limited. PMID- 17270772 TI - Vibration absorbing brace for study of work-related upper extremity musculoskeletal disorders. AB - The use of hand-held power tools can result in absorption of significant vibration energy by the worker's hand and arm, and is a causal factor in the development of various muskuloskeletal disorders (MSD's) such as carpal tunnel syndrome (CTS) and hand-arm vibration syndrome (HAYS). A novel brace incorporating vibration damping materials is proposed that could reduce this energy absorption, resulting in lower incidence of vibration-related occupational MSD's. The National Occupational Research Agenda (NORA) has identified this type of injury as a priority research area. The proposed brace will have utility in the top three NORA-sponsored areas for research tools and approaches: clinical assessment of exposure to environmental vibration; practical use as improved personal protective gear; and evaluating the effects of reduced vibration exposure on MSD incidence. Clinical test results for prototype braces on human volunteers are reported: splints with piezoelectric material showed a median improvement of 12% in vibration damping as compared to otherwise identical nonpiezoelectric splints (median allowable error of +/- 1.5%). The use of these splints to further study how the hand-arm system absorbs vibration energy is also discussed. PMID- 17270773 TI - System design for a pediatric physical therapy strength testing glove. AB - The goal of this project is to develop a strength testing glove that will improve current methods of muscle strength measurement by enabling physical and occupational therapists to quantitatively assess patient progress. The project was realized through research, human testing, prototype construction, component testing, and analysis of data. This design will provide a cheaper, more flexible, more versatile, and more quantitative method of muscle strength measurement for medical professionals. This design could potentially change the current approach pediatric physical therapists take in testing and tracking patients muscle strength. PMID- 17270774 TI - Physiological investigation of automobile driver's activation index using simulated monotonous driving. AB - Monotonous automobile operation in our daily life may cause the lowering of what might be termed an activation state of the human body, resulting in an increased risk of an accident. We therefore propose to create a more suitable environment in-car so as to allow active operation of the vehicle, hopefully thus avoiding potentially dangerous situations during driving. In order to develop such an activation method as a final goal, we have firstly focused on the acquisition of physiological variables, including cardiovascular parameters, during presentation to the driver of a monotonous screen image, simulating autonomous travel of constant-speed on a motorway. Subsequently, we investigated the derivation of a driver's activation index. During the screen image presentation, a momentary electrical stimulation of about 1 second duration was involuntarily applied to a subject's shoulder to obtain a physiological response. We have successfully monitored various physiological variables during the image presentation, and results suggest that a peculiar pattern in the beat-by-beat change of blood pressure in response to the involuntary stimulus may be an appropriate, and feasible, index relevant to activation state. PMID- 17270775 TI - An unobtrusive in-home monitoring system for detection of key motor changes preceding cognitive decline. AB - The existing paradigm of ongoing or posttreatment monitoring of patients through periodic but infrequent office visits has many limitations. Relying on self report by the patient or their family is equally unreliable. We propose an alternative paradigm in which continuous, unobtrusive monitoring is used to observe changes in physical behavior over time. We highlight the use of this technique for monitoring motor activity that may be predictive of early cognitive changes in the elderly. Initial results using a system of low-cost wireless sensors are presented, together with a discussion of appropriate analyses and interpretation of such data. Using low-cost wireless sensor network coupled with algorithms to detect changes in relevant patterns of behavior, we are able to detect both acute and gradual changes that may indicate a need for medical intervention. PMID- 17270776 TI - Postural balance indicator and associated feedback compensation system. AB - Postural balance related disorders not only limit individual mobility but also often result in serious injuries or even death in particular in the elderly. Presented statistical data demonstrates the severity of this growing problem as the population at large is getting older. In addition, the disorders of the vesitibular system, often of idiopathic origin, and related abnormalities affect population across all age groups. Therefore, in order to provide an assessment of balance, awareness to patients, as well as continuous feedback to assist in maintaining equilibrium, a low cost unobtrusive system for postural balance management has been designed. The system is based on two designed and perpendicularly placed level sensors with optical detection, and a set of vibrators interfaced with the PIC based BS2 board by Parallax. The tilt identifiable vibrators provide a feedback. A programmable delay and curtailment of movement related superficial responses provides additional adaptability. The premise of this compact battery operated system is to assist patients in restoring mobility and gaining independence. PMID- 17270777 TI - Real-time blood cross-matching sensor for intelligent management of transfusion safety. AB - Blood transfusion errors are not uncommon. In some cases the error is fatal. This is primarily due to lack of an automated system at the point of application and over-reliance on bar-coding and paperwork to catch these critical errors. In emergency situations, human errors contribute to transfusion and transplantation of incompatible blood types and organs resulting in rejection and possible fatality. We present a sensing concept that will monitor blood compatibility between the patient and the transfusion bag before allowing the valve to open for transfusion to take place. This will eliminate all transfusion errors and provide 100% safe transfusions automatically. The operating principle of the sensor is based on the light scattering characteristics of dilute blood and the effect of agglutination on scattering. The device proposed is an optical system based on spectrophotometric methods. The device configuration, and results from several tests with combinations of known blood samples will be presented. PMID- 17270778 TI - Evaluation of endorectal and urethral cooling devices during MR-guided ultrasound thermal ablation in canine prostate. AB - High-temperature thermal therapy for the treatment of prostate cancer is currently being applied as a minimally-invasive alternative over traditional forms of treatment. Catheter-based interstitial and transurethral ultrasound applicators are being developed for controlled and selective thermal ablation of prostaric tissues with concurrent MR thermal imaging. As part of this treatment strategy we have devised a transurethral cooling catheter and a cooling jacket to be placed over the endorectal MR imaging coil to protect the urethral mucosa and rectal wall from thermal damage during treatment. The cooling efficiencies and protective abilities of these devices were evaluated in vivo within three canine prostate glands. Invasive and MR derived temperature measurements within the prostate and rectal wall indicate that the protective influence of the endorectal cooling extends 5-10 mm from the rectal wall into the dorsal prostate. The urethral cooling extends approximately 5 mm from the cooling balloon. The protective capabilities were further verified with subsequent histological analysis with TTC stained tissue sections and contrast enhanced T1-weighted MR images post treatment. Both of these cooling devices are compatible with the MR thermometry and can be used to protect the urethral mucosa and rectal wall during prostate thermal ablation with interstitial and transurethral ultrasound devices. PMID- 17270779 TI - Interstitial ultrasound applicators with dynamic angular control for thermal ablation of tumors under MR-guidance. AB - Thermal ablation has been investigated as a treatment for a variety of cancers. Heat treatments have not gained large-scale clinical acceptance due to inconsistencies in controlling heat deposition in vivo and the lack of precise temperature measurement. Interstitial ultrasound provide a good method of controlling the radial depth of a thermal lesion and the applicator designs evaluated in this study allow for dynamic angular control of the shape of the lesion. A trisectored internally water-cooled applicator (TriAD) and a rotating catheter water-cooled applicator (RIUS) angularly controlled thermal dose to a target area. Both devices were small in diameter (1.8 mm-2.4 mm), making them clinically feasible for minimally invasive treatment in device size-sensitive tissues. A biothermal model accounting for changes in acoustic attenuation and perfusion as a function of thermal dose was used to evaluate and predict applicator performance. The MR susceptibility artifact of the applicators was examined with MR temperature imaging (MRTI) sequences at 1.5 T and 0.5 T. Ex vivo experiments in turkey and beef muscle with realtime MRTI correlated well with results from the biothermal model. These results display the feasibility of thermally treating tumors with controllable interstitial ultrasound applicators under real-time MRTI and bracket the applicators' predicted performance in vivo. PMID- 17270780 TI - MRI-temperature mapping during ultrasound prostate ablation using fat for phase estimation. AB - Referenceless proton resonance frequency (PRF) shift thermometry provides a means to measure temperature changes during minimally invasive thermotherapy that is inherently robust to motion and tissue displacement. In this study, the method is expanded to allow background phase estimation from fatty tissue. A correction scheme for temperature map distortions caused by the ultrasound applicator is developed. The method is tested during thermal ablation of canine prostate using a directional transurethral ultrasound applicator. PMID- 17270781 TI - A device for radiofrequency assisted hepatic resection. AB - Hepatic resection is the current standard treatment for hepatic malignancies. During hepatic resection part of the liver containing the tumor is surgically removed. This type of surgery is associated with high blood loss of approximately 1 L. Blood loss is associated with increased complication rates, prolonged hospital stay and reduced patient survival, especially when transfusion is required. We present a device that allows coagulation of a plane of tissue 1 to 2 cm wide, including coagulation of large vessels. This enables reduction of blood loss to a minimum by performing surgery along the coagulated tissue plane. The device consists of a linear array of radiofrequency (RF) electrodes 1.5 cm apart. By application of RF current in bipolar mode between two adjacent electrodes, temperatures close to 100 degrees C are obtained in-between electrodes enabling coagulation of large vessels. Rapid switching of applied current between all adjacent electrode pairs enables rapid heating of a tissue slice. We present a prototype device including results from ex vivo and in vivo experiments. PMID- 17270782 TI - Investigation of medical thermal treatment using a hybrid bio-heat model. AB - Bio-heat transfer, - heat transfer affecting living organism under the influence of blood perfusion -, is given great and increasing attention in medicine today. One reason is the increasing use of thermal treatment methods in for example heart- and neuro-surgery. Analysis and modelling of the thermal aspects is frequently carried out at every stage of device and method development, as it exhibits unique possibilities to understand the complex interactions present. This work investigates the use of a hybrid bio-heat model/equation, which is subsequently used to analyse temperature measurement during thermal treatment of the prostate. PMID- 17270783 TI - Comparison between a detailed and a simplified finite element model of radio frequency lesioning in the brain. AB - A detailed and a simplified model of a lesioning electrode was made using the finite element method. 15 simulations of the lesioning procedure were performed for each model and the resulting lesion volumes were compared in order to investigate if the simplified model is adequate. The simplified model resulted in a very slight overestimation of the volume compared to the detailed model. It was thus concluded that the simplified model is adequate for simulations. PMID- 17270784 TI - Combination applicator for simultaneous heat and radiation. AB - We present the development of operator and patient friendly conformal applicators that can deliver moderate temperature hyperthermia simultaneously with radiation in superficial tissue overlying contoured anatomy. This applicator combines the uniform heating capabilities of large area conformal microwave array (CMA) flexible printed circuit board applicators with a patient interface (coupling bolus) that facilitates positioning of brachytherapy sources at a fixed distance (e.g. 1.5 cm) from the skin. A customized inverse treatment planning program (IPSA) was used to optimize spacing of a parallel array of source catheters and separation distance from skin, and to characterize the effects of bolus thickness and conformal array curvature on radiation dose uniformity. Performance of a 15 cmx15 cm combination applicator was evaluated in flat and contoured homogenous muscle tissue models. Results demonstrate effective heating and radiation distributions to 1-1.5 cm depth and out to the periphery of the array. This applicator should prove useful for treatment of diffuse chestwall disease located over contoured anatomy that is difficult to treat with external beam radiation. By applying heat and radiation simultaneously for maximum synergism of modalities, this device should expand the number of patients that can benefit from effective thermoradiotherapy for superficial disease. PMID- 17270785 TI - Optimization of a dual concentric conductor antenna for superficial hyperthermia applications. AB - Dual concentric conductor antennas (DCCs) have been proposed as effective radiators for microwave hyperthermia applications, due to simplicity of construction from flexible printed circuit board (PCB) material. With proper design, the power deposition (SAR) pattern is uniform across the DCC. The effect of a single antenna can be combined in conformal nonphased arrays to form a region of nearly flat temperature distribution over a large area down to 1-1.5 cm depth. In the past, DCC antenna performance was analyzed using in-house FDTD software. Recently available electromagnetic simulation software provides reduced simulation time, increased accuracy and a user friendly interface with the ability to sweep design parameters to achieve critical optimization goals. More detail on antenna loading conditions provides enhanced design accuracy by accounting for second order effects neglected in previous modeling. In particular, recent design efforts have focused on improving antenna efficiency and reducing losses and reflections in the feedline network. A second challenge involves measurement of antenna properties in conditions more similar to the treatment environment, since temperature and loading condition affect antenna radiation and thus design requirements. We present the challenges of both antenna design and characterization, along with preliminary results of recent design improvements. PMID- 17270786 TI - Design of spiral antennas for radiometric temperature measurement. AB - We are developing a microwave hyperthermia system for the treatment of chestwall recurrence of breast cancer. To improve power control of heating applicators, we intend to measure tumor temperature noninvasively during treatment, using radiometry. We are designing single-arm Archimedean spirals for use as receive antennas with a radiometer collecting thermal radiation from different tissue volumes at 1.9-2.3 and 3.7-4.2 GHz. We modeled the antennas numerically. First, we studied the antennas in terms of impedance matching to feedlines. Second, we investigated radiation mechanisms of the spirals radiating into lossy tissue. For small spacing between turns, the surface currents on the spiral were in phase on several neighboring windings, producing strong radiation from a circular, wavelength related region. At these locations, surface currents were also in phase on opposite sides of spiral, contributing to a more centrally peaked radiation pattern with deeper energy penetration than is obtained with a widely dispersed pattern. Finally, we studied the effect of distance from the spiral feedpoint to the radiating region on antenna efficiency. We found this distance should be minimized to reduce power loss from the less useful inner turns of the spirals. The optimization of these design parameters may produce significant improvement of antenna efficiency and improve depth-sensing capability of microwave radiometry. PMID- 17270787 TI - Coaxial-slot antenna for interstitial microwave thermal therapy and its application to clinical trial. AB - The authors have been studying thin coaxial-slot antennas for interstitial microwave thermal therapy. In this paper, firstly, the structure of the coaxial slot antenna is briefly reviewed. Secondly, the procedure for temperature calculation around the antennas and the calculation model based on the CT images of the patient are described. Thirdly, the blood flow rate of the tissue concerned during the treatment is estimated from the temperature transition during the treatment. Finally, the temperature distribution in and around the tumor is calculated based on the estimated blood flow rate and some conditions for the actual treatment. PMID- 17270788 TI - Increased acoustic and electromagnetic energy deposition in a layered tissue model. AB - By analyzing and optimizing acoustic and electromagnetic waves absorption in a simplified layered model of hyperthermic configuration, it is shown that the commonly used attenuation metrics are not always proper means for determining the generally optimal parameters of typical thermal therapy problem with finite extent target The conditions, parameters and bounds for optimal (maximal) incident power absorption for the layered model have been found analytically and explicitly and are presented in terms of basic wave propagation characteristics, thus, also providing the necessary data for optimal synthesis of absorbing tissues and materials. PMID- 17270789 TI - Cell-lab on a chip: a CMOS-based microsystem for culturing and monitoring cells. AB - We describe a MEMS-on-CMOS microsystem to encage, culture, and monitor cells. The system was designed to perform long-term measurements on arrays of single electrically active cells. A MEMS process flow was developed for the fabrication of closeable microvials to contain each cell, a custom bio-amplifier CMOS chip was designed, fabricated, and tested, and the fabrication of the MEMS structures on this chip was demonstrated. In addition, bovine aortic smooth muscle cells were plated on the surface, and over the course of a week they adhered, formed processes, and reproduced, verifying the compatibility of the materials used with the cell culture. PMID- 17270790 TI - Optical measurement of torsional spring modulus of a double-stranded DNA using half-coated nanoparticles. AB - A technique of detecting the rolling and spinning of half-coated nanoparticles using interference ring patterns of the fluorescence has been applied to the measurement of torsional spring modulus of a double-stranded DNA. Using the unique ability to measure nanoparticle rotations in multiple degrees of freedom, we were able to determine the spinning of a nanoparticle tethered on the DNA and thereby the twisting of the DNA in real time. The detailed knowledge of the spinning as well as rolling behaviors of half-coated nanoparticles provides information about torsional elastic properties of the DNA under investigation. PMID- 17270791 TI - Development of biocompatible parylene neurocages. AB - We present a refined method and design for building parylene neurocages for in vitro studies of live neural networks. Parylene neurocages are biocompatible and very robust, making them ideally suited for studying the synaptic connections between individual neurons to gain insight into learning and memory. The neurocage fabrication process is significantly less complex than earlier versions. Previous neurocage designs achieved limited neuronal outgrowth; however, the long-term cell survival rate was <25%. The incorporation of new materials and different anchoring techniques, in addition to some design modifications, as outlined here, have improved the long-term cell survival rate to >50%. PMID- 17270792 TI - Development of a multifunctional platform for extra- and intracellular ionic activities recording. AB - We present the development of a multifunctional platform equipped with an array of silicon nitride micropipettes with dimensions allowing the implementation of extra- and intracellular operations. Micropipettes with outer diameter that ranges from 6 mum down to 300 nm and with walls thicknesses of 500 down to 150 nm are presented. The generic technology developed to fabricate these micropipettes has a number of advantages, including the ability to be implemented as ion selective electrodes for (A) intracellular and (B) extracellular recordings and as (C) local drug microdispensers. PMID- 17270793 TI - Effects of scaling on the SNR and speed of biosensors. AB - This work presents a stochastic model for the observed signal of biosensors, a model that predicts the signal fluctuation of the system and the SNR associated with it using a Markov chain process. In the process, transition probabilities are derived from the target and probe binding kinetics in view of statistical motion and random walk events. Based on this model, we are able to estimate the settling time, power-spectral density (PSD), and signal to noise ratio (SNR) of general affinity-based biosensors. The effects of scaling from macroscopic to microscopic regimes are also studied, which indicate a fundamental tradeoff between settling time (speed) and signal fluctuation (noise). The model is also applied to analyze the behavior of a DNA hybridization electronic detector. PMID- 17270794 TI - Surface plasmon resonance biochips for tuberculosis bacillus detection. AB - Tuberculosis is one of notifiable infectious diseases which may cause serious epidemic problems. Traditional diagnostic techniques include acid-fast stain, bacteria culture, metabolic monitoring have some disadvantages such as low sensitivity, time consumption and less specificity. In this study we proposed a new diagnostic technique based on the protein chips concept which detected by SPR phenomena. It was found that the resonance angle approximately 51.86 degrees ) shifted slightly toward right with antibody concentration of 10X, 30X, 100X, and 300X dilution under optimal concentration of immobilized TB antigen W38 (MW 41.5 kDa, 50 mug/ml). While for the W06 (MW 14 kDa, 50 mug/ml), the resonance angle was around 50.13 degrees and shifted with the same trend as W38 did. PMID- 17270795 TI - Electrical detection of the contact between a microinjection pipette and cells. AB - This work presents the basic design and tests of a device designed for detecting the contact between a microinjection pipette and cell membrane. The device facilitates the automation of the microinjection procedure of living adherent cells. The measurement of the contact is based on measuring the resistance of the pipette. Breakage and clogging of the pipette can be detected with the same measurement. PMID- 17270796 TI - Hybrid polymer/thin film impedance system for label free monitoring of cells. AB - Impedance measurements (capacitive cytometry) have been used to perform label free analysis of cells. Two devices were constructed using a simple liquid photopolymerization technique known as muFluidicTectonics. This platform has made it possible to rapidly fabricate with great ease and without the use of traditional MEMS technology a cell impedance measurement system. Measurements were made using not only a single 1 kHz frequency but also a frequency sweep from 50 Hz to 20 kHz. Single frequency measurements on SP2 mouse cells showed show that there is a strong, linear relationship between the DNA content of individual cells and their dielectric (or capacitance) response to a 1 kHz field. Frequency sweeps were conducted on SF9 cells as means to perform diagnostic measurements of the device when different number of cells are present. PMID- 17270797 TI - Biochemical, biomolecular and cellular sensing in microfluidics using flow induced admittance spectra. AB - We present flow induced admittance spectra for electrolytes, cell culture media, different sizes of DNA solutions and neural cells using flow induced admittance spectra in a microfluidics device. The device comprises of a PDMS channel aligned with a pair of channel electrodes fabricated on glass. The peak of the flow induced admittance spectra and frequency at which the peak occurs are the key parameters used for the characterization of sensing. The response of this sensor is a function of the conductivity and dielectrivity of the effective solution. The flow induced admittances of the particles studied are corrected with their media. This sensing will be a primary component of an electrical based cytometer. PMID- 17270798 TI - Biological sensing with an on-chip resistive pulse analyzer. AB - Resistive pulse sensors (or Coulter counters) detect the conductance change caused by single fluid-borne particles transiting a pore. Their simplicity in design and use, along with their capability for single-molecule sensitivity, make them well-suited to the analysis of biological particles. Here, we use standard methods of micro- and nanolithography to construct resistive-pulse devices that combine microfluidics with electronic sensing. We use the devices to detect single latex colloids, single DNA molecules, and specific antibody/antigen binding. We discuss the advantages of our design, and prospects for future applications. PMID- 17270799 TI - High-throughput cell manipulation using ultrasound fields. AB - A method is presented for high-throughput cell manipulation that is capable of trapping and transporting biological cells in liquid using acoustic forces in an ultrasound field. The authors applied this technique for concentrating several cell types such as HeLa cells and human mesencymal stem cells. More than 90% of the cells were successfully concentrated into desired patterns. They also investigated cell viability in ultrasound fields and found little adverse effect. This work demonstrates that ultrasonic cell manipulation is suitable for being integrated into lab-on-a-chip systems for trapping and transporting large numbers of cells rapidly and is promising in cell fractioning. PMID- 17270800 TI - Droplet-based magnetically activated cell separation. AB - In this study, we developed a method that target cells in suspension can be separated by combining magnetic force and gravitation force. Since the newly developed method involves a separating process of a droplet containing nontarget cells in suspension by applying magnetic force to separate target cells, we called it droplet-based magnetic activated cell sorting (dMACS). To demonstrate the efficiency of the dMACS system, Ter119 (+) cells from mouse bone marrow cells were separated by both conventional MACS and our dMACS systems. Effects of three parameters on separation efficiency were examined in the dMACS system. As a result, both volume of droplet of cell suspension, and magnetic force did not affect the efficiency of cell separation markedly. However, the time for cell settlement in the droplet showed a critical role in the efficiency of cell separation according to increasing time. Therefore, we tried to verify that the saturation time affected increase of its efficiency and that flow rate injected to get rid of the negative cell resulted in the decrease of its efficiency. Using this dMACS system, we were able to pinpoint that the flow rate of cell suspension injected into a magnetic platform results in disturbance in the droplet, leading to turbulence in the cell suspension. PMID- 17270801 TI - MEMS-based flow cytometry: microfluidics-based cell identification system by fluorescent imaging. AB - This study utilizes MEMS technology to realize a novel low-cost microfluidics based biochip system for flow-type cell handling. Powered by vacuum pump, the microfluidic driving system enables cells to move in order one by one in the biochip by an effect of sheath flow prefocus. Then, cells are guided to a fluorescent inspection region where two detection tasks such as cell image identification and cell counting are conducted. Currently, the glass-based biochip has been manufactured and all the related devices have been well set up in our laboratory. With this proposed prototype system, typical results about cell separation of yeast cell and PC-3 cell are available and their separated images are also presented, respectively. PMID- 17270802 TI - Nanomanipulation and characterization of structural proteins. AB - A methodology is presented for simultaneous mechanical testing and atomic force microscopy imaging of single collagen fibrils under load. This method holds the promise for determining single-fibril modulus and strength in various experimental preparations. Examples of this utility include characterization of deformation and failure modes of naturally occurring and engineered structural proteins. Additional promise of this technique is robotic surgery at the submicron scale for repairing neuronal tracts and capillaries with structural proteins. A series of algorithms for tying knots at the nanoscale in single fibrils is also presented. PMID- 17270803 TI - Cytometry microchip using polymer-based saltbridge electrodes. AB - We developed a cytometry glass chip using polymer-based saltbridge electrodes. Saltbridge electrodes were placed at lateral sides of channel to increase the sensitivity and robustness of detection. The dimension of saltbridge electrodes which are exposed to channel was 50mum by 20mum (width, height). The saltbridge electrode was formed at a specific position in a predefined shape by photopolymerization technique. UV light sensitive monomer DMAC (dially dimethyl ammonium chloride) was used for polymerization. Polymer-based saltbridge electrode enabled the DC impedance analysis of the channel for cytometry. Moreover, the lateral positioning of saltbridge electrode is easily accomplished by photopolymerization technique. We validated the detection sensitivity of developed chip using 10mum fluorescent bead. PMID- 17270804 TI - Finite element modelling of a 3 dimensional dielectrophoretic flow separator device for optimal bioprocessing conditions. AB - Planar 2-dimensional dielectrophoresis electrode geometries are limited in only being capable of handling fluid volumes ranging from picolitres to hundreds of microliters per hour. A 3-dimensional electrode system has been developed capable of handling significantly larger volumes of fluid. Using finite element modeling the electric field distribution within various bore sizes was realized. From these simulations it is possible to optimize bioprocessing factors influencing the performance of a dielectrophoretic separator. Process calculations have shown that flow-rates of 25ml hr/sup -1/ or more can be attained for the separation of heterogeneous populations of bio-particles based on their dielectric properties. PMID- 17270805 TI - Novel micro gripping, probing, and sensing devices for single-cell surgery. AB - Several novel devices under development in our laboratories to ultimately realize a micro robotic system for single cell nanoscale probing, injection, imaging and surgery is described in this paper. Thus far, we have 1) developed MEMS polymer grippers that can be actuated under water with very large deflection and are capable of gripping 500mum embryonic cells in water with approximately 2 V input; 2) developed a probe-etching technique to controllably shape fiber probes into various tip geometries, i.e., fibers with initial diameter of 125 mum were sharpened into tips with angles ranging from <2.7-9.7 degrees and with nanoscale tip diameters of <1mum; 3) developed a novel PVDF force sensing system with resolution in the sub-muN range for applications in bio-manipulation, bio injection, and potentially single cell surgery. Details of these technologies are discussed in this paper. PMID- 17270806 TI - Flagellar motor based micro hybrid devices. AB - We are in the process of developing a series of micro hybrid devices based on tethered flagellar motors. Examples of the devices include a microfluidic pump and a micro AC dynamo. The microfluidic pump is realized through the tethering of a harmless strain of Escherichia coli cells to a MEMS based micro channel. Each E. coli cell is about 3 mum long and 1 mum in diameter, with several flagella that are driven at the base by molecular rotary motors. The operational principle of the micro pump is based on the viscous pumping effect where continuous rotation of the tethered cells forms a fluidic conveyor belt that 'drags' fluid from one end of the channel to the other. We used hydrodynamic loading to synchronize cell rotation in order to maximize the fluid pumping capability. The micro dynamo is realized through the integration of tethered flagellar motors with micro ferromagnetic beads and micro copper coils. The micro dynamo generates AC power by using the tethered cells to create a rotating magnetic field around the copper coils. Preliminary result indicates a high power density when compared to other biologically based micro power generators. PMID- 17270807 TI - RET nanobiosensors using affinity of an apo-enzyme toward its substrate. AB - Fluorescent biosensors can be highly specific and sensitive, and may be engineered as implantable devices for metabolic monitoring. Commonly-used systems for glucose monitoring based on resonance energy transfer (RET) and competitive binding involve Concanavalin A (Con A), which is known to be toxic, and has problems of aggregation and irreversible binding. This work presents an improved RET assay wherein Con A was replaced by apo-glucose oxidase (apo-GOx). Fluorescence measurements confirm that the apo-GOx/dextran complexes are highly sensitive to glucose, observed as an increase in the donor peak relative to acceptor with the stepwise addition of glucose solution. The assay showed strong signals and excellent repeatability, with a sensitivity of 9x10/sup -4/ (ratio units)/mM over the range of 0-90 mM glucose. If properly encapsulated, these sensors can potentially be used for in vivo sensing without the concern of toxicity associated with Con A. PMID- 17270808 TI - Shape recovering of live endothelial cell under atomic force microscopy imaging. AB - When live endothelial cells imaged using atomic force microscopy (AFM), distortion of the cell shape could be caused by the interaction between the probe and cell membrane, which depends on the force and the scanning speed used. In this study, a shape recovering method was developed. Two forces were considered in the method: the vertical and the lateral force of the tip exerted on the cell membrane during the scanning. The cell membrane was modeled as an elastic material. Results show that the recovering is necessary to reveal the original cell shape. The AFM tip effect should be taken into consideration in the live cell morphological study using AFM. PMID- 17270809 TI - Development of a MEMS microsystem to study the effect of mechanical tension on cerebral cortex neurogenesis. AB - A clamp-and-ratchet microstructure based on poly crystalline silicon (polysilicon) microelectromechanical systems (MEMS) technology has been designed to exert mechanical tension along radial glial processes between groups of neural stem cells to study the effect of tension on cerebral cortex neurogenesis. FEA analysis shows that the design should not fail under expected loading conditions. Preliminary studies show that embryonic brain tissue survives under tension for at least six days. Neurospheres have been successfully cultured on Poly(dimethylsiloxane) (PDMS) for eight days and exhibit radial extensions which appear to support neuronal migration. Stretching the PDMS using the clamp and ratchet will produce tension in these radial extensions which may modulate neuronal migration, a key process in cerebral cortex development. PMID- 17270810 TI - Biomolecule separation by steric hindrance using nanofluidic filters. AB - Micro/nanofluidics technologies can be used to solve toughest challenges in the biomolecule analysis. It is now possible to fabricate nanofluidic channels with the dimension of 30-500 nm, and these nanofluidic structures have been formerly used to separate large DNA molecules where molecular dimension is larger than the nanofluidic filter gap size. In this work, we demonstrate separation of biomolecules (DNA and proteins) that are smaller than the nanofluidic filter gap size. This is possible due to the steric hindrance effect of the biomolecules; the entropy of biomolecules has to be decreased for the molecules to enter the nanofluidic filter, which leads to the free energy barrier for the molecular transport. Double stranded DNA molecules as small as 100 bp approximately 34 nm extended length), as well as SDS-coated proteins have been separated in a nanofluidic channel that has the filter gap thickness between 60-120 nm. This result clearly shows the potential of using nanofluidic filters as a sieving medium for smaller biomolecules such as proteins. Compared with traditional random nanoporous materials such as gel or polymer monolith, nanofluidic channels can be made precisely to have a pre-determined 'pore' size and shape, which allows characterization and optimization of biomolecule separation process. PMID- 17270811 TI - Microfluidic system integration in sample preparation chip-sets - a summary. AB - An increasing complexity of microfluidic chips and systems used for biochemical assay applications calls for the development of new strategies towards their functionality integration in order to achieve optimum assay performance. Approaches to an integration of microfluidic chips into diagnostic fluidic systems are reviewed with the emphasis on the selection of assay application, integration scheme, interfacing, and fabrication platform. In particular, we discuss a system containing polymer microfluidic chip-sets capable of cell pre concentration from a complex sample matrix using immunomagnetic separations. PMID- 17270812 TI - Microfabricated templates for the electrodeposition of metallic barcodes for use in multiplexed bioassays. AB - Lithographically defined polyimide templates were prepared using microfabrication techniques. The templates consist of high aspect ratio pores that were formed by deep plasma etching. Different metals are electrodeposited into the pores, and then the template is removed to allow the metallic rods (particles) to be released into solution. The striping pattern of metals on the particles is used to optically identify the particles. Particles range in size from 0.6 mum in diameter by 7.7 mum in length to 4.2 mum by 27 mum in length. These particles have been evaluated in a multiplexed DNA hybridization assay. PMID- 17270813 TI - Control of concentration and volume gradients in microfluidic droplet arrays for protein crystallization screening. AB - A novel screening platform for the screening and optimization of protein crystallization is reported. Here we present two key experiments to generate protein crystallization phase diagrams. One is to precisely generate spatial gradient droplet arrays; the other is to trap and identify each droplet in place in order to carry out temporal and spatial analysis. The generated concentration and volume gradient ranges from 0% to 100% and from 155 to 310 pico liters, respectively. Furthermore, the active trapping of a droplet array in a microfluidic chip for hours to days to study the dynamic phase changes in protein crystallization is demonstrated. This microfluidic platform can be used for rapidly generating the solubility diagram for protein in various salt solutions. PMID- 17270814 TI - Separation of blood in microchannel bends. AB - Most clinical chemistry tests are performed on cell-free serum or plasma. Therefore micro assay devices for blood tests require integrated on-chip microfluidics for separation of plasma or serum from blood. This is achieved by a new blood separation technique based on a microchannel bend structure developed within the collaborative microtele-biochip muTBC) project co-funded by the German Ministry for education and research (BMBF). Different prototype polymer chips have been manufactured with an UV-LIGA process and hot embossing technology. The separation efficiency of these chips has been determined with samples of human whole blood as well as diluted blood samples. The results show different separation efficiencies up to 90% for blood cells and plasma depending on microchannel geometry as well as cell concentration. As compared to present microfluidic devices for the separation of blood cells like filters or filtration by diffusion the microchannel bend is an integrated on-chip blood separation method, which combines the advantages of rapid separation times and a simple geometry. PMID- 17270815 TI - High speed particles separation using ultrasound for microTAS and lab-on-a-chip application. AB - Engineers have long envisioned that a handheld portable blood diagnosis device would be able to give an accurate measurement of chemical content based on a very small sample in the shortest time possible. One of the immediate applications of such device is the point of care (POC) diagnosis system, whereby a single drop of human blood would determine his health status. However, a major technical challenge lies in the ability to separate different particles, which in the case of human blood, is to separate red and white blood cells and plasma in a quick, cheap, reliable device with low power consumption. In this paper, we present some preliminary results from our tests of ultrasound standing waves as a potential separation mechanism for blood cells. Also, we report on the study of the behavior of suspended particles of the size equivalent to a human cell under the influence of ultrasonic acoustic field, using micro particle image velocimetry (PIV) measurement technique. This provides the fundamental understanding and foundation of designing an integrated microchannel structure that can provide ultrasonic cell separation in the microscale regime. The study has shown promising results of successfully separating two different particles based on their sizes difference. PMID- 17270816 TI - An examination of the effect of an AC pulsed electric field on cell mortality in SWLA-2 hybridomas. AB - This work describes the initial experimental setup and results involving the percentage cell lysis in SWLA-2 murine hybridomas produced by AC electric field pulses of varying amplitudes and pulse widths. Cells were cultured and separate samples examined at 24 hours. The frequency, pulse width and peak-to-peak voltage were varied. AC electric fields producing at least 1 V across the cell membrane appear to be more effective in producing cell lysis than similar fields producing lower membrane voltages. Additionally, higher frequencies, in the 10 kHz range, appear to be more effective than lower frequencies at membrane voltages above 1 V in producing cell lysis. PMID- 17270817 TI - A magnetically driven PDMS peristaltic micropump. AB - We present a robust low-cost PDMS peristaltic micropump with magnetic drive. The fabrication process is based on the soft molding and bonding of three PDMS layers. A base layer incorporates the microchannel while a middle layer contains the actuation membrane. The top layer encapsulates three small permanent magnetic rods (Ni-plated-NdFeB) in three small chambers. A small DC motor (6 mm in diameter and 15 mm in length) with three permanent magnets stagger-mounted on its shaft is used to pull down and actuate the membrane-mounted magnets to generate a peristaltic waveform. A maximum pumping rate of about 24 muL/min at the speed of 1700 rpm with power consumption of 11 mW was demonstrated. A preliminary numerical analysis of the peristaltic pump was performed, which showed the characteristic membrane deflection and fluid flow of pumping. PMID- 17270818 TI - An examination of the effect of decaying exponential pulse electric fields on cell mortality in murine spleenocytes, hybridomas, and human natural killer cells. AB - This work describes the percentage cell lysis produced by exponentially decaying electric field pulses of varying amplitudes and time constants. Three different cell types were examined: murine spleenocytes, hybridomas, and human natural killer. Cells were cultured and separate samples examined at 24 hours and 48 hours. Two sets of experiments were performed for each cell type. At 0.3 kV, the spleenocytes exhibited a mortality of roughly 50% twenty-four hours after exposure to the pulse; while at forty-eight hours the spleenocyte cell count had reduced to roughly 25% viable cells. All other cell types showed mortality consistently in excess of 80% at field pulse strengths of about 0.3 V/m. PMID- 17270819 TI - Quantitative and qualitative analyses of DNA fragments based on electrical charge detection on a portable electrophoresis device. AB - A concept regarding DNA fragments electrophoretic analyses by directly detecting electrical charges is proposed. The arrival time and voltage of charged DNA fragments with different charge-to-mass ratio could be detected using the custom made micro electronic circuits. These time and voltage information imply the size and intensity information acquired from the conventional slab gel image by fluorescent labeling. A prototype of the portable electrophoresis device consists of a flow channel with the dimension of 35 mm (length) x 0.5 mm (width) x 0.2 mm (depth) on an acrylic substrate, and the detection circuit with amplification gain of 10,000 and analogous filter bandwidth between 0.1 Hz and 10 Hz has been developed. A simple experiment was carried out to demonstrate the feasibility of proposed idea. The volume of 2mul of the DNA ladder (1 Kb Plus DNA ladder, Invitrogen, U.S.A.) with the diluted concentration of 0.1mug/mul was loaded into the reservoir when applying the electrical field of 12.5 V/cm to both end of the flow channel, which was only filled with TBE solution. The preliminary results showed that the developed electrophoresis device can pick up the electrical signals of un-separated DNA fragments with total mass of 0.2 mug , and the magnitude is 0.6 V . Micro flow channels fabricated by an excimer-laser machine and low-noise amplifier with high gain, e.g. 100,000 are being processed. Moreover, HEC (hydroxyethylcellulose) solution will be utilized as the media in the micro channels for DNA fragments separation. PMID- 17270820 TI - A magnetically driven PDMS micropump with microball valves. AB - We present a novel robust PDMS membrane micropump with two one-way microball valves for biomedical applications. The actuating membrane is driven by magnetic force of two miniature permanent magnets. The micropump consists of two PDMS layers, one holding the microball valves and actuating chamber and the second holding the top magnet and covering the chamber and microvalves. A simple approach is used to fabricate a high performance microball valve using an embedded Teflon/sup trade mark/ microtube. A small DC motor (6mm in diameter and 15mm in length) with two permanent magnetic discs (NdFeB) mounted on its shaft is used to actuate the membrane-mounted magnet. This configuration yields a large pumping rate with very low power consumption. Maximum pumping rate of 260muL/min was achieved at the input power of 21mW, the highest pumping rate reported in the literature for micropumps at such power consumption. PMID- 17270821 TI - Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. AB - To overcome skin's barrier properties that block transdermal delivery of most drugs, we and others have microfabricated arrays of microscopic needles, primarily out of silicon or metal. This study addresses microneedles made of biocompatible and biodegradable polymers, which are expected to improve safety and manufacturability. To make biodegradable polymer microneedles with sharp tips, we adapted microelectromechanical masking and etching to produce beveled tip and chisel tip microneedles and developed a new fabrication method to produce tapered-cone microneedles using an in-situ lens-based lithographic approach. To replicate microfabricated master structures, PDMS micromolds were generated and a novel vacuum-based method was developed to fill the molds with polylactic acid, polyglycolic acid and their copolymers. Mechanical testing of the resulting needles measured the force at which needles broke during axial loading and found that this failure force increased with Young's modulus of the material and needle base diameter and decreased with needle length. Failure forces were generally much larger than the forces needed to insert microneedles into skin, indicating that biodegradable polymers can have satisfactory mechanical properties for microneedles. Finally, arrays of polymer microneedles were shown to increase permeability of human cadaver skin to a low-molecular weight tracer, calcein, and a macromolecular protein, bovine serum albumin, by up to three orders of magnitude. Altogether, these results indicate that biodegradable polymer microneedles can be fabricated with an appropriate geometry and sufficient strength to insert into skin, and thereby dramatically increase transdermal transport of molecules. PMID- 17270822 TI - Remotely adjustable check-valves with an electrochemical release mechanism for implantable biomedical microsystem. AB - We present two remotely adjustable check-valves with an electrochemical release mechanism for implantable biomedical microsystems. Using these valves, one can vary the opening pressure set-point and flow resistance over a period of time. In the first design, an array of remotely addressable valves with a SU-8 structural polymer layer deposited on the top of a gold sacrificial layer act as the micromachined check-valve. In an alternative design, the set point is changed by varying the length of a cantilever-beam. The adjustable cantilever-beam structure is fabricated by gold thermo-compression bond of a thin silicon wafer over a glass substrate. The evaporated gold forms anchors on the silicon and strips on the glass substrate. Adjustment of both microvalves is based on electrochemical dissolution of gold using a constant DC current obtained via a telemetry link. A current density of 35mA/cm/sup 2/ is used to activate the valves. Both gravity and syringe-pump driven flow are used to characterize the valve performance. The multistage fluidic performance (e.g. flow resistance and opening pressure) is clearly demonstrated. PMID- 17270823 TI - Real time 3D detection of nanoparticle liposomes extravasation using laser confocal microscopy. AB - Laser confocal microscopy was used to study the real time 3D transport of nanoparticles in tumor and normal tissues under normal hyperthermic conditions. Breast tumor was inoculated to the nude mouse dorsal skin flap window chamber. Rhodamine labeled liposome nanoparticles were injected into the mouse tail vein. The hyperthermic condition was imposed on the tumor through a thermal chamber. Real time 3D images of extravasation of liposome nanoparticles in normal and tumor tissues were reconstructed. Transport of the nanoparticles from the vasculature to the interstitial space was quantified by measuring both spatial and temporal fluorescence intensity variations. Results show that the liposome nanoparticles hardly extravasate into the interstitial of normal tissues under both normal and hyperthermic conditions. The extravasation of the nano-particles in tumor tissues was greatly enhanced by increasing the local temperature to 42 degrees C. The confocal images show that the extravasation of the nanoparticles in tumor is heterogeneous, and depends on the tumor angiogenesis. PMID- 17270824 TI - In vivo transfection microsystems. AB - Transfection is currently used to insert molecules into cells. In vivo transfection is mainly performed via viral or chemical transfection. However, electrical transfection is known to be a more efficient way to insert drugs into cells without side effects. In spite of this advantage, not too many devices allow to perform electrotransfection in vivo because of their invasiveness. Here we present a new microfluidic microdevice which is small enough to be inserted into deep region with a minimum of drawbacks. Therapeutic molecules, genes or drugs can be injected into targeted tissues. High voltage electric impulsions can be applied. This device offers the advantage to be a stand alone device with a 500 mum square section. This generic tool can be used for drug delivery, electrotransfection as well as electrostimulation. PMID- 17270825 TI - Implantable microchips for controlled drug delivery. AB - We report on the development of an implantable drug delivery system capable of delivering multiple individual doses. This product controls the release of potent therapeutic compounds that might otherwise require frequent injections. The system will provide stable, hermetic storage of therapeutic drugs, such as proteins and peptides, in solid, liquid, or gel form. Because discrete doses are stored individually, multiple-drug regimens of pulsatile or continuous release are possible. The microchip drug release technology has been evaluated in release studies in vitro and in vivo. Here we describe one such study. The method of drug release was successfully demonstrated and found to be reliable and repeatable. PMID- 17270826 TI - Cell adhesion testing using novel testbeds containing micropatterns of complex nanoengineered multilayer films. AB - Methods for producing biomaterial patterns with defined spatial distribution micro- and nano-scale features are important for studying the cellular-level interactions, including basic cell-to-material and cell-to-cell communications. This work reports on the fabrication of substrates to study cell adhesion to multicomponent micropatterns of multilayer films by coupling conventional photolithography and LbL techniques, known as the L-LbL technique. Toward this end, substrates with nanofilm micropatterns of two different bio-functionalities have been fabricated for sPLA/sub 2/ and PLL and were used for in vitro cell culture studies using neurons, which exhibited preferential and high efficiency and selective adhesion to sPLA/sub 2/ nanofilms. These results support the immediate use of multicomponent micropatterns as biological testbeds for basic studies of cells, and provide a basis for further expansions of the fabrication processes to produce scaffolds for precise definition of cell-to-material and cell-to-cell interactions, such that the resulting constructs mimic in vivo cell organization and behavior. PMID- 17270827 TI - Long-term micropatterned cell cultures in heterogeneous microfluidic environments. AB - Microfluidic poly(dimethylsiloxane) (PDMS) devices were constructed and used as long-term cell culture platforms for skeletal muscle cell differentiation and for dynamic application of chemical stimuli to the cells. The devices featured two orthogonal fluidic networks: one for long-term cell perfusion at minimal rates and the other one for short-term selective cell treatment and stimulation with biologically relevant molecules. The cells were micropatterned within the microfluidic channels using surface modification techniques, cultured under continuous flow, and allowed to fuse into polynucleated myotubes (a major milestone in muscle cell differentiation). By exposing cells to heterogeneous laminar flows, it was possible to confine a membrane receptor labeling assay to a region smaller than a cell. PMID- 17270828 TI - Real three-dimensional microfabrication for biodegradable polymers: demonstration of high-resolution and biocompatibility for implantable microdevices. AB - We have developed a novel three-dimensional (3D) microfabrication method for biodegradable polymers. Unlike conventional processes, our process satisfies high resolution and high-speed requirements. The system design allows us the processing of microlevel forms by stacking up melted polymers from the nozzle. We adopted a batch process to supply materials in order to eliminate the prior process that required toxic solvents. In addition, it is possible to handle almost all biodegradable thermoplastic resins by adopting this system. A single layer from the piled-up layers of extruded lines was observed to evaluate the resolution. The lateral and depth resolutions attained are 40 mum and 45 mum, respectively. Biodegradable polymers enable three-dimensional microstructures such as micropipes, microbends, and microcoil springs to be manufactured in less than 15 min. The biocompatibility of the newly fabricated structure was evaluated using a cell line (PC12). For this purpose, a small vessel, with a transparent base, was fabricated using PLA and cells were cultivated in it. The results were then compared with the results obtained using the standard method. Our system renders it possible to produce toxic-free, as well as transparent and leakage free devices. Our system is expected to have potential applications in optimum design and fabrication of implantable devices, especially in tissue engineering. PMID- 17270829 TI - Electrolytically generated oxygen microgradients for cell culture. AB - We present a microdevice capable of electrochemically generating user-defined oxygen gradients for use in cell and tissue culture. Electrolytic dissolved oxygen generation at multiple electrodes evolves 1D and 2D oxygen gradients across several millimeters with microscale precision and has the potential to test the effect of localized oxygen doses on a wide range of tissue and cell samples. The developed microgradients are stable for days, enabling experiments of physiologically relevant duration. We present the basic theory of operation and initial results. PMID- 17270830 TI - Robotic assessment of locomotor recovery in spinal contused rats. AB - The purpose of this study was to investigate the ability of a robotic device, "the rat stepper", to assess intrinsic locomotor recovery following spinal cord contusion injury in adult rats. The device consists of a motorized body weight support mechanism that precisely controls the load to the hindlimbs during stepping, and two small robotic arms that measure and manipulate hindlimb movement. Sixteen rats received a contusion injury to the mid thoracic spinal cord with different severity levels (mild, moderate, severe, and sham). The animals were then evaluated weekly using the rat stepper, beginning one week after injury and continuing for a period of twelve weeks, across a range of body weight support levels. The contused animals demonstrated recovery in a standard locomotor assessment score (the BBB score), with most of the recovery occurring by four weeks post injury. We analyzed fourteen robotic measures of stepping and found that the measures that were most sensitive to intrinsic recovery were step velocity and inter limb coordination. These measures were also significantly correlated with the BBB score. The number of steps taken during testing was not sensitive to intrinsic recovery, nor correlated to the BBB score. These results suggest that step quality, rather than quantity, best reflects recovery after contusion injury in adult, untrained rats. Thus, robotic motion capture of only a few steps can provide a sensitive, valid measure of locomotor recovery after contusion. PMID- 17270831 TI - Passive derivation of basic walker-assisted gait characteristics from measured forces and moments. AB - This work describes a method that passively assesses basic walker-assisted gait characteristic, including heel strikes, toe-off events, as well as stride time, double support and right & left single support phases using only force-moment measurements from the walker's handles. The passively derived gait characteristics were validated against motion capture gait analysis and showed good correlations. This research is part of an effort that aims to identify user intent, from measuring forces and moments exerted on the handles of the walker as well as from perceiving the environment, and to incorporate identified intent into a passive shared steering control system for the walker. The primary focus of the work leading to This work is to identify the double support phase, and to engage the steering control at the beginning of this phase to maximize the user's stability. However, the application of the method presented and the instrumented walker can be extended to longitudinal outside the lab Gait assessment. PMID- 17270832 TI - Gravity balancing rehabilitative robot for the human legs. AB - People with severe muscle weakness from neurological injury, such as hemiparesis from stroke, often have substantial limitations. The focus of rehabilitation after stroke is often on walking function, however, equipment available to facilitate walking function is severely limited. Most devices move patients through predetermined movements rather than allowing the patient to move under their control. This work presents the design of a gravity balancing rehabilitative robot to assist persons with both leg impairment to walk through elimination of the effects of gravity. The design of the machine is based on a hybrid method for gravity balancing, with two steps: (i) locate the center of mass of a machine using auxiliary parallelograms; (ii) select springs to connect from the center of mass such that the total potential energy of the system is invariant with configuration. The design of the machine considers all motions of the leg and the pelvis by assuming the center of mass of pelvis to be located on the line joining the two hip joints. Preliminary version of this machine, with limited features, is being fabricated. PMID- 17270833 TI - Virtual walkway system and prediction of gait mode transition for the control of the gait simulator. AB - A virtual walkway system is proposed in This work. This system consists of a new developed gait simulator and a HMD system to present virtual space to the user. The gait simulator is designed to permit the user to walk straight, change direction, go up and down stairs, etc. Main part of this gait simulator is two foot plates driven by three arms and actuators. Each foot plate follows the foot during swing phase and pulls it back during the stance phase while the user is walking straight However this gait simulator has one weak point, that is, this simulator cannot follow the change of gait mode sufficiently, like the start of walking or the end of walking. To solve this problem it is necessary to predict the change of gait mode to follow the transition perfectly. In this paper we chose the start and the end of straight walking and have tried to measure this transition of gait mode. To do this we paid attention on the anterior bending of the upper trunk. It is expected that the trunk bends forward before the start of walking and bends back before the stop of walking. In the experiment the distance between the upper trunk and the center of gravity (COG) was measured and it was proven that the measurement of this distance showed to be useful to know the transition of straight walking. This result was examined again on the gait simulator. Implanted control algorithm of gait simulator is as follows; two foot plates pull back the feet when the start of walking was predicted and stop when the stop of walking was predicted. Results show that the gait simulator was able to reproduce the start and the end of walking by this prediction algorithm. PMID- 17270834 TI - Safety concept for robotic gait trainers. AB - The work presents a newly developed safety concept for application of robotic walking simulators based on the principle of programmable footplates in gait rehabilitation. Unlike robotic hand devices or exoskeleton robots for gait training on treadmills, which can be built relatively lightweight and require only small drives which can hardly do harm to the patient, a programmable footplate walking simulator with permanent foot fixture essentially needs to have powerful drives in order to carry and move the full body weight of the patient. The developed safety concept comprises several redundant algorithms and devices in the real-time robot control software, electrical emergency stop circuitry and machine mechanics. The mechanical core is a machine design offering maximum passive security by covering all moving parts (i.e. robot drives and linkages) and a newly developed foot safety release binding, which is mounted on each footplate. The release binding allows a safe release from the footplate in all directions in any degree of freedom in the sagittal plane. It is combined with an ankle goniometer which is equipped with adjustable emergency stop limit switches, thus ensuring that the allowed ankle range-of-motion is not exceeded. PMID- 17270835 TI - Experimental demonstration of an actuated exercise machine. AB - Experimental results are obtained for a single degree of freedom prototype next generation exercise machine that aims to maximize the user's power output and ensure passivity with the user. In an effort to optimize the user's power expenditure, the desired velocity trajectory is developed that seeks the unknown user-dependent optimal velocity setpoint. A numerical extremum-seeking algorithm is utilized to seek the optimal velocity setpoint while ensuring the trajectory is sufficiently differentiable. To track the reference trajectory and to ensure passivity, a nonlinear controller is utilized. PMID- 17270836 TI - A pneumatic muscle hand therapy device. AB - Intensive repetitive therapy improves function and quality of life for stroke patients. Intense therapies to overcome upper extremity impairment are beneficial, however, they are expensive because, in part, they rely on individualized interaction between the patient and rehabilitation specialist. The development of a pneumatic muscle driven hand therapy device, the Mentortrade mark, reinforces the need for volitional activation of joint movement while concurrently offering knowledge of results about range of motion, muscle activity or resistance to movement. The device is well tolerated and has received favorable comments from stroke survivors, their caregivers, and therapists. PMID- 17270837 TI - Exoskeleton for forearm pronation and supination rehabilitation. AB - Loss of function after SCI, ABI or stroke has a marked affect on ones quality of life. Return of function has been a long-standing goal of physical and occupational therapy. Repeated motor practice has been identified as crucial for motor recovery. The development of a robotic device for neuromotor rehabilitation and upper extremity neuromuscular system recovery is described. The actuator mechanism allows free motion when possible, and provides programmable therapeutic levels of resistance. The sensor system allows characterization of the applied forces, and accurate measurement of the range of motion of the joint. The control system provides real time feedback of actuator commands based on sensor data, calibration routines, and operational modes. PMID- 17270838 TI - Utilization of biomechanical modeling in design of robotic arm for rehabilitation of stroke patients. AB - Stroke is one of the leading causes for long-term disability in the United States. Robot-aided rehabilitation has facilitated the functional recovery of chronic stroke victims. In this study, two models were developed to aid the design of a rehabilitation robot driven by pneumatic muscle (PM) actuators, which will be applied in the treatment of the upper-limb sensorimotor deficits of stroke patients. A biomechanical model of the musculoskeletal system with exoskeleton robot powered by PM was implemented to examine the initial parameters of PM based on the kinematics and dynamics of PM assisted arm-reaching and self feeding tasks. The outputs of the model provided guidelines for the optimal design of robot's structure. Additionally, the model can determine the necessary auxiliary force and the activation timing pattern of each PM during multi-joint coordinated movement for the robot's dynamic control. Inverse-dynamics biomechanical model generates the joint torques required to perform the movement. In addition to the musculoskeletal model, we propose a simple method to estimate the self-generated net muscle torques, therefore, to provide quantitative assessment of motor improvement of stroke patients during the therapy. PMID- 17270839 TI - Adaptive assistance for guided force training in chronic stroke. AB - This work describes a novel form of robotic therapy for the upper extremity in chronic stroke. Based on previous results, we hypothesized that a training task that encourages subjects to consciously guide endpoint forces generated by the hemiparetic arm will result in significant gains in functional ability of the arm, superior to more conventional methods of therapy. In addition, since stroke survivors present with varying degrees of arm movement ability, we developed an adaptive algorithm that tailors the amount of assistance provided in completing the guided force training task. The algorithm adapts a coefficient for velocity dependent assistance based on measured movement speed, on a trial-to-trial basis. The training algorithm has been implemented with a simple linear robotic device called the ARM Guide. One participant completed a two month training program with the adaptive algorithm, resulting in significant improvements in the performance of functional tasks. PMID- 17270840 TI - Spring over muscle (SOM) actuator for rehabilitation devices. AB - For people affected by stroke, frequent physical therapy has been shown to be an effective form of rehabilitation. To this goal, several home therapy devices have been developed. Many of these devices may benefit from the use of a bidirectional pneumatic muscle actuator. This work presents the concept and design of the double-acting, compliant, spring over muscle (SOM) actuator. The principle design uses a spring in parallel with a pneumatic muscle actuator. This concept is economical, and easily scalable. Additionally, a design proposal for an ankle rehabilitation device, which incorporates the SOM actuator, is discussed. PMID- 17270841 TI - Trajectory generation for robotic needle insertion in soft tissue. AB - Accurate needle insertion in soft, inhomogeneous tissue has been a major concern in several recent studies involving robot-assisted percutaneous therapies. In procedures that involve multiple needle insertions such as transrectal ultrasound guided prostate brachytherapy, it is important to reduce tissue deformation before puncture and during insertion. In order to reduce this deformation, we have studied the effect of different trajectories for a 2-DOF robot performing needle insertion in soft tissue. We have compared tissue deformation and infinitesimal force per tissue displacement for different trajectories. According to the results of our experiments, infinitesimal force per displacement is a useful parameter for online trajectory update. Our proposed position/force controller is shown to provide considerable improvement in performance with regard to tissue deformation before puncture. PMID- 17270842 TI - Static and dynamic accuracy of vitreoretinal surgeons. AB - Accuracy in manual manipulation in a simulated microsurgical environment has been studied. Three vitreoretinal microsurgeons completed a series of static and dynamic tasks. Results for overall rms position error, overall maximum position error, and estimated physiological tremor amplitude were calculated. The rms amplitude of the error vector in three dimensions averaged 166 mum in a stationary pointing task, and 2009-4506 mum in the dynamic tasks. The maximum error vector magnitude during the stationary task averaged 408 mum during the stationary tests, and 3531-6788 mum in the dynamic tasks. The rms amplitude of tremor during the stationary task averaged 76-101 mum in the three spatial coordinates, with an average vector magnitude of 156 mum rms. PMID- 17270843 TI - Active tremor compensation in microsurgery. AB - This work presents the development of an intelligent microsurgical instrument to perform real-time tremor compensation within a handheld tool. The intelligent instrument senses its own motion, distinguishes between voluntary and erroneous motion, and manipulates its tip to cancel the undesired component in real-time. The on-board sensing unit is made up of a magnetometer-aided all-accelerometer inertial measurement unit and sensor fusion is performed via a quaternion-based Kalman filtering. Tremor is modeled and filtered by an adaptive zero-phase notch filter. The intraocular shaft manipulator is a three DOF piezoelectric actuated mechanism driven by a feedforward controller with inverse rate-dependent hysteresis model. Laboratory experimental results of the system are presented. PMID- 17270844 TI - Robotic control in hand-assisted laparoscopic nephrectomy in humans - a pilot study. AB - Computer-assisted surgical devices, including laparoscopic surgical robotic arms, can be used in urologic surgery to minimize trauma. In this study, we explored the feasibility and applicability of using a robotic arm, AESOP (Computer Motion Inc, Goleta, CA), as a substitute for surgical assistants during hand-assisted laparoscopic nephrectomies in humans. Four patients (3 men and 1 woman, mean age 66 years) underwent robotic-assisted laparoscopic nephrectomy. The hand-assisted laparoscopic nephrectomy was completed successfully in all patients. The average operative time, estimated blood loss, and time to hospital discharge was 252.5 minutes, 0.57 ml, and 4.5 days, respectively. Postoperative satisfactory function was confirmed through laboratory tests, imaging exams and biochemical tests. No complications were reported for any of the patients. Parameters, such as the operative time, are expected to be further reduced when more experience with the use of the robot has been acquired. In conclusion, robotic-assisted laparoscopic nephrectomy is feasible and safe, and can be performed without complications. The potential long-term cost effectiveness of using robotic surgical assistants in laparoscopic surgery highlights the economic impact of this research and warrants further investigation. PMID- 17270845 TI - A haptic guidance tool for CT-directed percutaneous interventions. AB - We have developed a new navigation approach for computer-assisted interventional radiology. Our system combines a virtual reality display with high-fidelity haptic rendering to provide assistance and guidance of the medical gesture. Specifically, the system is designed to improve the accuracy of blind needle placement within tissues. The proposed technique actively helps the surgeon while keeping him in control of the procedure. We have recently developed an experimental setup for CT-guided biopsy. The setup features a high-precision haptic device connected to the biopsy needle, combined with a graphical interface. The haptic system guides the surgeon's hand to the target tissue based on CT data, whereas a real-time, graphical visualization of the tool trajectory provides navigation information. The setup requires rigid registration of the patient with respect to the haptic interface. Tests have been performed in the presence of radiologists to validate the proposed concept, and early results show that the system is easy to use and requires little training. We are planning to conduct clinical testing in the near future to quantitatively assess system performance. PMID- 17270846 TI - An Er:YAG laser bone cutting manipulator for precise rotational acetabular osteotomy. AB - Rotational acetabular osteotomy (RAO) has an important advantage in that surgical bony defects are reconstructed with a patients' own tissue. We propose a surgical robot for the RAO using Er:YAG laser irradiating mounted on iliac bone to operate RAO precisely and to reduce recovery and trauma. A water-cooling Er:YAG laser (30 J/cm/sup 2/, l=2.94 mum, 20 Hz, 200 msec) that used optical fiber was operated 4 8 irradiation-overlapping ratio. We kept the distance between the laser and the bone at 0.25 mm using force sensor and spring to maintain effective ablation. Swine scapulae were ablated and performance was evaluated. The manipulator was operated mounting on iliac bone to get a filed position whereby resulting in precise bone cutting. The precision of the manipulator was within 0.3 mm and the efficiency of laser bone ablations per unit time optimized to 0.21 mm/sup 3//secW at the overlapping ratio of the irradiation area was 0.8, meaning a given ablated area was irradiated five times. The troughs showed m charring at this condition and the temperature of the surface was raised to 41.3 degrees C and it lasted only 5 seconds. We are sure that this research will be applied to orthopedics in the near future. PMID- 17270847 TI - Determining deformation resistance in cutting soft tissue with nonuniform thickness. AB - Understanding soft tissue response during tool tissue interaction is important for developing a reality based haptic interaction model for surgical training and simulation. In this work, experiments were conducted to cut liver specimens with nonuniform thickness. Three cutting speeds ranging from 0.1 cm/sec-2.54 cm/sec were used. The cutting forces, cutting tool displacement, and tool/tissue imaging via stereo camera system were collected. The time varying depth-of-cut in the thickness-varying specimen was then determined using image analysis. The force displacement data revealed that the cutting process consisted of a sequence of repeating units each comprising of a localized deformation phase followed by localized crack extension phase in the tissue. Based on depth-of-cut normalized cutting force, the deformation resistance of the tissue during the localized deformation phases was determined. The deformation resistance was characterized via the local effective modulus (LEM) of the soft tissue. The effect of cutting speed on the deformation resistance of the soft tissue was determined. PMID- 17270848 TI - Soft-tissue material properties under large deformation: strain rate effect. AB - Biomechanical model of soft tissue derived from experimental measurements is critical for developing a reality-based model for minimally invasive surgical training and simulation. In our research, we have focused on developing a biomechanical model of the liver with the ultimate goal of using this model for local tool-tissue interaction tasks and providing feedback to the surgeon through a haptic display. We are interested in finding the local effective elastic modulus (LEM) of the liver tissue under different strain rates. We have developed a tissue indentation equipment for characterizing the biomechanical properties of the liver and compared the local effective elastic modulus (LEM) derived from experimental data with plane stress, plane strain, and axisymmetric element types in ABAQUS under varying strain rates. Our results show that the experimentally derived local effective modulus matches closely with the plane stress analysis in ABAQUS. PMID- 17270849 TI - Simulating complicated human birth for research and training. AB - We report on the design, testing and implementation of a novel birthing simulator developed specifically to research the delivery process and improve clinical training in uncommon but inevitable complicated human births. The simulator consists of a maternal model and an instrumented fetal model, used in conjunction with an existing force-sensing system and a data-acquisition system. The maternal model includes a bony, rotatable pelvis, flexible legs, and a uterine expulsive system. The fetal model, which can be delivered repeatedly through the maternal model, is instrumented with potentiometers to measure neck extension, rotation and flexion during delivery. Simulation of the brachial plexus within the model fetal neck allows measurement of stretch in those nerves at risk for injury during difficult deliveries. Wooden elements mimic the properties of neonatal bone and can break either spontaneously or purposely. Two methods for measuring clinician-applied force during simulated deliveries provide trainees with real time assessment of their own traction force and allow researchers to correlate fetal neck motion and nerve stretch parameters with clinician-applied traction. Preliminary testing indicates the system is biofidelic for the final stages of the birthing process, and can be used for training and research in obstetrics. PMID- 17270850 TI - Locomotion of a legged capsule in the gastrointestinal tract: theoretical study and preliminary technological results. AB - This work illustrates the analysis of locomotion in the gastrointestinal tract obtainable by a legged capsule for diagnostic and therapeutic purposes. A preliminary simulation of the legged locomotion onto slippery and deformable substrates has been performed and -simultaneously- mechanisms for on board actuation of the legs have been developed and tested. Moreover, an engineering translation of medical needs in endoscopy is presented, with some ad hoc solutions for improving diagnostic capabilities. PMID- 17270851 TI - Applied force during vitreoretinal microsurgery with handheld instruments. AB - Applied force was measured in vivo during vitreoretinal surgery in rabbits, in three types of task: membrane peeling, vessel puncture/cannulation, and vessel dissection. Quantitative results are presented and compared with similar measurements taken in vitro in a porcine retina, in which no scleral interaction is present. PMID- 17270852 TI - A study on implantable urination assist systems - development of a bladder compression system. AB - We propose an urination assist system implantable in a patient who has difficulty in urination caused by the neuropathic bladder in order to assist the urination. The proposed system assists the urination by directly pushing the bladder of the patient using shape memory alloys (SMA). Peltier elements are used to control the temperature in the system. The effectiveness of the proposed system is evaluated by experiment with a bladder model. PMID- 17270853 TI - The BlastNP: a novel, sensitive sequence similarity searching method using overlappingly translated sequences. AB - An alternative method to TblastX has been developed, known as blastNP. Nucleic acids in database and query sequences were translated into overlapping protein like sequences (overlappingly translated sequences or OTSs) before searching with blastP. Thus, each nucleic acid sequence is represented by a single "protein like" sequence (instead of three hypothetical proteins in different reading frames). The BlastNP method is defined as a BlastP that is performed on an overlappingly translated nucleic acid database using a similarly converted nucleic acid query. The specificity and sensitivity of blastNP and TblastX is quantitatively very similar, except that blastNP is more sensitive to detect short sequence similarities (less than 50 residues). However, a qualitative comparison of the observed similarities showed that only 56% was detected by both methods, but 22% was indicated only by blastNP and 22% only by TblastX. For example, a statistically significant similarity between prion protein (PrP) and transcriptions factors (TF) was only detected by blastNP. A signal amplification was seen when OTS sequences were used in similarity visualisation methods (like LALIGN) instead of nucleic acids. PMID- 17270854 TI - Order independent structural alignment of circularly permuted proteins. AB - Circular permutation connects the N and C termini of a protein and concurrently cleaves elsewhere in the chain, providing an important mechanism for generating novel protein fold and functions. However, their in genomes is unknown because current detection methods can miss many occurrences, mistaking random repeats as circular permutation. Here we develop a method for detecting circularly permuted proteins from structural comparison. Sequence order independent alignment of protein structures can be regarded as a special case of the maximum-weight independent set problem, which is known to be computationally hard. We develop an efficient approximation algorithm by repeatedly solving relaxations of an appropriate intermediate integer programming formulation, we show that the approximation ratio is much better than the theoretical worst case ratio of r=1/4. Circularly permuted proteins reported in literature can be identified rapidly with our method, while they escape the detection by publicly available servers for structural alignment. PMID- 17270855 TI - Corpus based learning of stochastic context-free grammar combined with hidden Markov models for tRNA modelling. AB - tRNA molecule has a well-known second structure in which it folds by pairing of far-off nucleotides. This paper shows a syntactic pattern recognition methodology for model tRNA second structure using stochastic context-free grammars. In order to learn models, structural regions (paired nucleotides) have been learned from categorized samples with full labelled tree with a Corpus based estimation algorithm. Nonstructural regions have been modelled by hidden Markov models and transformed to stochastic regular grammars to fusion together the structural regions. Test with positive samples and negative samples in comparison with Sakakibara achieved 1.81% in sequences error rate, 98.43% in precision and 100% in recall and 100% of SER in negative test. Corpus based algorithm is computational time efficient and required less training samples for converge to the correct model of the tRNA second structure. PMID- 17270856 TI - Globally optimal classification and pairing of human chromosomes. AB - We investigate globally optimal algorithms for automated classification and pairing of human chromosomes. Even in cases where the cell data are incomplete as often encountered in practice, we can still formulate the problem as a transportation problem, and hence find the globally optimal solution in polynomial time. In addition, we propose a technique of homologue pairing via maximum-weight graph matching. It obtains the globally optimal solution by forming all homologue pairs simultaneously under a maximum likelihood criterion, rather than finding one pair at a time as in existing heuristic algorithms. After the optimal homologue pairing, chromosome classification can also be done by maximum-weight graph matching. This new graph theoretical approach to chromosome pairing and classification is more robust than the transportation algorithm, because many attributes of a chromosome have less variations within a cell than between different cells. PMID- 17270857 TI - Finding the best ridge regression subset by genetic algorithms: applications to multilocus quantitative trait mapping. AB - Genetic algorithms (GAs) are increasingly used in large and complex optimization problems. Here we use GAs to optimize fitness functions related to ridge regression, which is a classical statistical procedure for dealing with a large number of features in a multivariable, linear regression setting. The algorithm avoids overfitting, gracefully handles collinearity, and leads to easily interpretable results. We use the method to model the relationship between a quantitative trait and genetic markers in a mouse cross involving 69 F2 mice. The approach will be useful in the context of many genomic data sets where the number of features far exceeds the number of observations and where features can be highly correlated. PMID- 17270858 TI - A software system for gene sequence database construction. AB - We propose a Web-based software system for sequence database construction. An example application of this system is to construct a ribosomal RNA gene (rDNA) sequence database to facilitate the study of microbial communities. A fast and accurate approximate string-matching algorithm is implemented to fetch rDNA sequences sandwiched by two given primers from GenBank. A homology search algorithm based on Basic-Local-Alignment-Search-Tool (BLAST) is then used to extract rDNA sequences that do not contain the primers. This two-step process leads to an rDNA sequence database for a specific taxonomic group. We consider the distance between two given primers, mismatches and degeneracy when performing string matching. In the homology search, a chaining algorithm is combined with BLAST to obtain global alignments based on local alignments. This system can be used in many biological applications. PMID- 17270859 TI - An interpolated Markov model polishes Gibbs sampling's ability in detecting regulatory elements. AB - Microarray techniques provide new methods to find coregulated genes based on their coexpression profiles. Under the assumption that coregulated genes share cis acting regulatory elements, it is important to investigate the upstream sequences controlling the transcription of these genes. A modified Gibbs sampling algorithm with background interpolated Markov model (IMM) has been developed to detect regulatory elements in the upstream regions of translation start site of coexpressed genes. Simulated data are used to test our algorithm successfully. Results show that the improved Gibbs sampling has better performance in extracting less-conserved elements than algorithms with single nucleotide independent model and fixed higher-order Markov models. Then, upstream sequences of two clusters of coexpressed genes from Saccharomyces cerevisiae under diauxic shift conditions are analyzed, several putative motifs that may be involved in the pathway are found. PMID- 17270860 TI - A three-layer multidatabase system for functional statistical analyses of microarray experiment results. AB - New high-throughput technologies available for the post-genomic era, such as the microarrays, produce lists of hundreds of genes candidate regulated, or with particular expression profiles, in the conditions under study. These lists need to be biologically interpreted to gain a better knowledge of the pathophysiological phenomena involved. To this aim, several biological annotations are available within heterogeneous and widely distributed databases. Although numerous tools have been developed for annotating lists of genes, most of them do not provide methods for evaluating the relevance of the annotations provided, or for estimating the functional bias introduced by the gene set on the array used to identify the considered gene list. To reach this goal, we developed GFINDer, Genome Function INtegrated Discover, a Web-accessible three-layer multidatabase system that automatically provides large-scale lists of user classified genes with functional profiles biologically characterizing the different gene classes in the list. GFINDer automatically retrieves annotations of several functional categories from different sources, identifies the categories enriched in each class of a user-classified gene list, and calculates statistical significance values for each category. It also enables to functionally classify genes according to user-selected criteria and to analyse the resulting classifications, aiding in better biologically interpreting microarray experiment results. PMID- 17270861 TI - EGOMiner: a comprehensive genomics and proteomics data analysis and biological function interpretation system. AB - EGOMiner, stands for enhanced gene ontology mining system, is a CORBA based tool developed for genomic and proteomic data analysis. One key function of EGOMiner is to provide biological data interpretation based on gene ontology with quantitative and statistical analysis and visualization by direct acyclic graph. Cross comparison of multiple experimental studies is supported. The other function is quality analysis of microarray chip images. The input is raw chip data and output is visualization of the data quality of the chip image. This is system significantly improves the GoMiner system that was designed and developed by the authors. PMID- 17270862 TI - A general probabilistic model of the PCR process. AB - This work describes a general probabilistic model for the PCR process; this model includes as a special case the Velikanov-Kapral model where all nucleotide reaction rates are the same. In this model the probability of binding of deoxynucleoside triphosphate (dNTP) molecules with template strands is derived from the microscopic chemical kinetics. A recursive solution for the probability distribution of binding of dNTPs is developed for a single cycle and is used to calculate expected yield for a multicycle PCR. The model is able to reproduce important features of the PCR amplification process quantitatively. This model also suggests that the amplification process itself is highly sensitive to initial concentrations and the reaction rates of addition to the template strand of each type of dNTP in the solution. PMID- 17270863 TI - A parallel implementation of the Smith-Waterman algorithm for massive sequences searching. AB - Efficient biological sequence searching is an important and challenging task in bioinformatics. Among those fundamental sequence analysis algorithms, the Smith Waterman algorithm that adopts the dynamic programming mechanism provides very high sensitivity. Unfortunately, the inefficiency in performance of this algorithm limits its applications in the real world. With the advances in the engineering technology, massive parallelism can be achieved using the FPGA-based techniques. A parallel implementation methodology of the Smith-Waterman algorithm is presented. This method provides magnificent speedup over the traditional sequential implementation, while maintain the same level of sensitivity. PMID- 17270864 TI - Identifying gene ontology concepts in natural-language text. AB - Gene-related discoveries are appearing in increasing volume in the scientific literature. The gene ontology (GO) provides standard ways of describing gene related information, but GO terms seldom appear in their exact form in natural language text. This paper describes a new tool, a biomedical text analyzer, for extracting GO terms and their variants from biomedical text. PMID- 17270865 TI - The search for the optimal ribosome 3' tail end in E. coli. AB - The 16s ribosomal tail end has been conjectured to play an important role in the regulation of protein production and of translation efficiency. Using E. coli K 12 as our model organism, we generate sequences of 13 base pairs as hypothetical ribosome tail ends. We analyzed the distributions of these random hypothetical ribosome tail ends and found the actual E. coli ribosome tail end to be significantly different from a randomly generated ribosome tail in the magnitude of the lock and synchronization signals, and the signal to noise ratio. We then designed and ran a genetic algorithm to optimize hypothetical ribosome tail ends simultaneously for these three signal criteria. We found that the actual E. coli ribosome tail end was among the best by these measures. PMID- 17270866 TI - Optimal nonlinear scoring function for global fitness landscape of protein design. AB - Protein design aims to identify sequences compatible with a given protein fold but incompatible to any alternative folds. To select the correct sequences and to guide the search process, a design scoring function is critically important. It is also important that a design scoring function can characterize the global fitness landscape of many proteins simultaneously. We describe how finding optimal design scoring functions can be understood from two geometric viewpoints, and propose a formulation using mixture of Gaussian kernel functions. We give results of distinguishing native sequences for a major portion of representative protein structures from a large number of alternative decoy sequences. We succeeded in deriving nonlinear scoring function that perfectly discriminate a set of 440 representative native proteins of known protein structures from 14 million sequence decoys. We show that no linear scoring function can have perfect discrimination. In an independent blind test using 194 unrelated proteins, our scoring function misclassifies only 13 native proteins. This compares favorably with 37 or 51 misclassifications when optimal linear functions reported in literature are used. PMID- 17270867 TI - Representability of genomic signals. AB - The paper presents a simple novel approach to data representability, based on the concept of relative data variation for a pixel. Typical cases of signals are analyzed from the representability point of view, with the focus on genomic signals. It is shown that the variation of genomic data along nucleotide sequences, specifically the cumulated and unwrapped phase of complex genomic signals, can be visualized adequately as simple lines for low and large scales, while for medium scales (up to several hundred samples per pixel) the approach used for statistical data representation must be used. PMID- 17270868 TI - Splice site detection using pruned maximum likelihood model. AB - In this paper we propose a novel method for splice site prediction using the maximum likelihood model. We performed maximum likelihood over the acceptor and donor datasets, and calculated sensitivity to measure the prediction performance. Then, by aggressive pruning of less informative nucleotide sites, while maintaining the high sensitivity of the method, we improved the model's performance in terms of the computational speed. In addition, after pruning fewer nucleotide sites need to be tagged, which in turn simplifies the development of an assay. The proposed method was tested on the human splice dataset. The results indicate that the proposed method was successful at splice site prediction with optimal sensitivity. PMID- 17270869 TI - Linear reduction methods for tag SNP selection. AB - It is widely hoped that constructing a complete human haplotype map will help to associate complex diseases with certain SNP's. Unfortunately, the number of SNP's is huge and it is very costly to sequence many individuals. Therefore, it is desirable to reduce the number of SNP's that should be sequenced to considerably small number of informative representatives, so called tag SNP's. In this paper, we propose a new linear algebra based method for selecting and using tag SNP's. Our method is purely combinatorial and can be combined with linkage disequilibrium (LD) and block based methods. We measure the quality of our tag SNP selection algorithm by comparing actual SNP's with SNP's linearly predicted from linearly chosen tag SNP's. We obtain an extremely good compression and prediction rates. For example, for long haplotypes (>25000 SNP's), knowing only 0.4% of all SNP's we predict the entire unknown haplotype with 2% accuracy while the prediction method is based on a 10% sample of the population. PMID- 17270870 TI - Building phylogenetic trees from binary oligonucleotide fingerprint vectors. AB - Oligonucleotide fingerprinting of ribosomal RNA genes (OFRG) is a method that permits the identification of microorganisms through ribosomal RNA gene (rDNA) analysis. OFRG sorts arrayed rDNA gene clones into clusters through a series of hybridization experiments, each using a single oligonucleotide probe. This series of hybridization experiments generates a "fingerprint" for each rDNA done. The fingerprints are binary vectors that specify whether the probes hybridized or did not hybridize to the clones. Identification of the microorganisms is accomplished by clustering fingerprints from unidentified clones with those from identified clones. The most accurate taxonomic classifications from rDNA analysis are often obtained through complete nucleotide sequence analysis. However, the direct information that we acquire from OFRG is the presence or absence of a specific substring of nucleotides in the unidentified rDNA sequence. This paper provides several ways to associate information to the set of fingerprints obtained by OFRG. PMID- 17270871 TI - Free energy periodicity in prokaryotic coding and its role in identification of +1 ribosomal frameshifting in the Escherichia Coli K-12 gene prfb. AB - This work reports on a novel signal processing method that can be applied to analysis of genetic sequences in prokaryotes to identify their translational characteristics. The methodology involves computation of a signal based on free energy score of the interaction between the 3' tail end of the 16S rRNA and the mRNA sequence of interest. We find that in the coding region of prokaryotes this signal is has a strong harmonic corresponding to every 3/sup rd/ base position. Noncoding regions appears not have such a signal. We discuss the methodology in detail and we demonstrate its ability to clearly recognize a) the coding region of a single prokaryotic gene, and b) special characteristics of the gene, such as frameshifts. We use E. Coli K-12 genes to illustrate the findings. PMID- 17270872 TI - Automatic segmentation of DNA bands in one dimensional gel images produced by hybridizing techniques. AB - Automatic segmentation of DNA bands in one dimensional DNA fingerprint gel images produced by hybridizing techniques could be challenging due to the noise and large intensity variation among the bands within each lane in the image. A new algorithm for automatic segmentation of DNA bands based on the variance (var), mean-variance-ratio (MVR) and equivalent width is presented. A number of pre processing steps should be applied on the image prior to the automatic segmentation. First a homomorphic filter is applied to enhance the image followed by an edge preserving noise filtering algorithm to remove the noise in the image. Then a background normalization operation is applied to the resulting image. After these preprocessing operations, each lane in the image is detected and presented by a one dimensional intensity profile. The new algorithm will be applied on the valleys in the resulting intensity profile for each lane to characterize the corresponding valley as noise or a DNA band. We have applied this algorithm on several DNA fingerprint gel images, and all the bands were successfully segmented, except the very weak (faint) bands which are very close to their background. These should be analyzed manually. PMID- 17270873 TI - Improvement of TRANSFAC matrices using multiple local alignment of transcription factor binding site sequences. AB - This paper describes a novel approach to constructing position-specific weight matrices (PWM) based on the transcription factor binding site (TFBS) data provide by the TRANSFAC database, and the comparison of the thus generated PWMs with the original TRANSFAC matrices. Multiple local sequence alignment was performed on the TFBSs of each transcription factor. Several different alignment programs were tested and their matrices were compared to the original TRANSFAC matrices. One of the alignment programs, GLAM, produced comparable matrices in terms of the average ranking of true positive sites across the whole test set of sequences. PMID- 17270874 TI - Codes in the codons: construction of a codon/amino acid periodic table and a study of the nature of specific nucleic acid-protein interactions. AB - The theory of "codon-amino acid coevolution" was first proposed by Woese in 1967. It suggests that there is a stereochemical matching - that is, affinity - between amino acids and certain of the base triplet sequences that code for those amino acids. We have constructed a common periodic table of codons and amino acids, where the nucleic acid table showed perfect axial symmetry for codons and the corresponding amino acid table also displayed periodicity regarding the biochemical properties (charge and hydrophobicity) of the 20 amino acids and the position of the stop signals. The table indicates that the middle (2/sup nd/) amino acid in the codon has a prominent role in determining some of the structural features of the amino acids. The possibility that physical contact between codons and amino acids might exist was tested on restriction enzymes. Many recognition site-like sequences were found in the coding sequences of these enzymes and as many as 73 examples of codon-amino acid co-location were observed in the 7 known 3D structures (December 2003) of endonuclease-nucleic acid complexes. These results indicate that the smallest possible units of specific nucleic acid-protein interaction are indeed the stereochemically compatible codons and amino acids. PMID- 17270875 TI - Accelerating phylogenetics computing on the desktop: experiments with executing UPGMA in programmable logic. AB - Having greater computational power on the desktop for processing taxa data sets has been a dream of biologists/statisticians involved in phylogenetics data analysis. Many existing algorithms have been highly optimized-one example being Felsenstein's PHYLIP code, written in C, for UPGMA and neighbor joining algorithms. However, the ability to process more than a few tens of taxa in a reasonable amount of time using conventional computers has not yielded a satisfactory speedup in data processing, making it difficult for phylogenetics practitioners to quickly explore data sets-such as might be done from a laptop computer. We discuss the application of custom computing techniques to phylogenetics. In particular, we apply this technology to speed up UPGMA algorithm execution by a factor of a hundred, against that of PHYLIP code running on the same PC. We report on these experiments and discuss how custom computing techniques can be used to not only accelerate phylogenetics algorithm performance on the desktop, but also on larger, high-performance computing engines, thus enabling the high-speed processing of data sets involving thousands of taxa. PMID- 17270876 TI - RNAMAT: an efficient method to detect classes of RNA molecules and their structural features. AB - There is a growing appreciation for the diverse and important roles RNA molecules play in cellular function. RNAMAT is an approach based on matrix representation of all potential base-pairing of a set of sequences to reveal common secondary structure features. When the RNA sequences come from one class, proper summation of these matrices exposes common structural features as demonstrated for tRNA and HACA-RNA. For C/D-RNA, a novel structural motif is suggested. Furthermore, it is demonstrated, in the case of tmRNA that the method can detect pseudo-knots which are structural motifs that are difficult to detect in other methods. When the sequences come from diverse sources, a specific clustering algorithm is suggested that is capable of detecting the common motifs. The algorithm is demonstrated in a case of a simulated example and in a real case derived from trypanosomes comparative RNomics study. PMID- 17270877 TI - Consequences of deterministic and stochastic modeling of a promoter. AB - For an engineered genetic oscillator, deterministic analysis indicates sustained oscillations and stochastic simulations show irregular or absent oscillations. Since the major difference is in the modeling of the promoters, we have performed a detailed analysis of a generic repressible promoter system. Deterministic, stochastic, thermodynamic, and hybrid models were developed for the promoter. The average behavior of the stochastic model converged to the thermodynamic model. The deterministic model is a special case of the thermodynamic model. The hybrid model could lock into the off state. Adding an unrelated background reaction allowed it to exit that state. Increasing the background rate allowed the hybrid model to converge to thermodynamic and stochastic model. Adding a background reaction to the stochastic oscillator simulation noticeably improved its performance. PMID- 17270878 TI - Synthetic gene oscillators by negative feedback networks. AB - We aim at developing a new methodology to model and design periodic oscillators of gene regulatory networks with multiple genes, proteins and time delays, by using multiple time-scale networks (MTN). Multiple time scale properties are exploited to simplify the model according to singular perturbation theory. We show that a MTN has no stable equilibria but stable periodic orbits. Finally, we design a biologically plausible gene oscillator by cI and Lac genes, to demonstrate our theoretical results. PMID- 17270879 TI - Cellular function prediction and biological pathway discovery in Arabidopsis thaliana using microarray data. AB - We have developed a new integrated probabilistic method for cellular function prediction by using microarray gene expression profiles, in conjunction with predicted protein-protein interactions and annotations of known proteins through an integrative statistical model. Our approach is based on a novel assessment for the relationship between correlation of two genes' expression profiles and their functional relationship in terms of the gene ontology (GO) hierarchy. We applied the method for function predictions of hypothetical genes in Arabidopsis. We have also extended our computational method using Dijkstra's algorithm to identify the components and topology of a pathway, and we applied it for predicting the signaling pathway of phosphatidic acid as a second messenger in Arabidopsis. PMID- 17270880 TI - Kernel based approach for protein fold prediction from sequence. AB - Due to the relatively large gap of knowledge between gene identification and gene function, the ability to construct a computational model describing gene function from sequence information has become an important area of research. In order to understand the biological role of a specific gene, we will require knowledge of the corresponding protein's structure and function. We present a support vector machines based method for determining a protein's fold from sequence information alone where this sequence has little similarity with sequences with known structures. We have focused on improvement in multiclass classification, parameter tuning, descriptor design, and feature selections. The current implementation showed better performance than previous similar approaches. PMID- 17270881 TI - Prediction of protein solvent profile using SVR. AB - We describe a support vector regression (SVR) approach to predict the accessible surface area (ASA) of a protein from its sequence. Our approach encodes each protein residue as a vector of amino acid propensities derived from a multiple alignment of the subject protein with homologous proteins. The vector consists of the log-likelihood ratios of each of the twenty amino acids in the residue's multiple alignment column. Using a reference set of proteins of known structure and, hence, known ASA, we trained an SVR model. Each training sample consists of the fifteen log-likelihood vectors in a window of width fifteen surrounding a residue, along with the "true" ASA value, computed from the known structure. To apply the model to proteins of unknown structure, only the subject protein sequence is required. Our method uses PSI-BLAST to simultaneously determine a set of (putative) homologs and compute the log-likelihood vectors needed to encode the subject protein. We show that this method provides substantially improved accuracy in predicting ASA when compared with an earlier method. PMID- 17270882 TI - Estimation of protein secondary structure from synchrotron radiation circular dichroism spectra. AB - A new approach to estimate the fraction of secondary structures fractions from synchrotron radiation circular dichroism (SRCD) spectra is presented. The protein SRCD spectra are first approximated using radial basis function networks (RBFN) and the resulting set is used to train a self-organising map (SOM). Thus the data are arranged in a two-dimensional map in such a way that most similar proteins are close to each other and vice versa. Estimation of the parallel and antiparallel beta sheets is discussed. The number of spectra in the training set is twenty four proteins and the protein under examination is also included in the set. Estimation results shows improvements compared with previous methods such as K2D and SOMCD. PMID- 17270883 TI - Modeling of the suprachiasmatic nucleus based on reduced molecular clock mechanisms. AB - One of the physiological substrates of circadian rhythms is known to be located in the suprachiasmatic nucleus (SCN), which unilaterally contains up to 10,000 or more pacemaker cells. Specific molecular clock mechanisms are working within each cell. Here, in order to prevent complexity explosion in understanding the dynamics of SCN, the molecular clock mechanisms are modeled in a reduced form preserving their dynamical characteristics. The reduced cellular models are coupled by diffusions of activating and suppressing agents so as to construct the whole SCN model. The resulting spatial patterns of entrainment are studied under varied diffusion constants. The simulation results suggest validity of reduction of the molecular dynamics as well as usefulness of the strategy employed to model the hierarchical biological system. PMID- 17270884 TI - Analysis of the transforming growth factor-beta/sub 1/ pathway and extracellular matrix formation as a hybrid system. AB - It is generally accepted that aging of the vascular system plays an important role in cardiovascular disease (CVD). Recent experimental findings have indicated the involvement of the cytokine transforming growth factor-beta/sub 1/ (TGF beta/sub 1/) in these vascular aging processes. This cytokine is, after binding to a cell receptor, associated with numerous cellular processes, including formation of the extracellular matrix (ECM, the biomolecular network that surrounds the cell). We implemented TGF-beta/sub 1/ signaling and its effect on ECM formation with piecewise-linear differential equations (PLDEs), which have several advantageous properties over traditional continuous modeling. Aging of the system was simulated as a reduction in cell sensitivity for TGF-beta/sub 1/. The model predicted a disturbed ECM balance during aging, which corresponds well to findings from the literature. The outcome of this hybrid approach was satisfactory and, therefore, we will continue modeling of various aging-related pathways with PLDEs in future research. PMID- 17270885 TI - Inference of genetic regulatory networks with recurrent neural network models. AB - Large-scale gene expression data coming from microarray experiments provide us a new means to reveal fundamental cellular processes, investigate functions of genes, and understand relations and interactions among them. To infer genetic regulatory networks from these data with effective computational tools has become increasingly important Several mathematical models, including Boolean networks, Bayesian networks, dynamic Bayesian networks, and linear additive regulation models, have been used to explore the behaviors of regulatory networks. In this paper, we investigate the inference of genetic regulatory networks from time series gene expression in the framework of recurrent neural network model. PMID- 17270886 TI - Parameter optimization technique using the response surface methodology. AB - We propose a parameter optimization technique using the response surface methodology (RSM) for the accurate biological cell simulation which calculates cell behavior by numerically integrating the differential equation and generates action potentials, intracellular Ca transient, contraction, and intracellular ATP consumption by using parameter values of major ion permeability and amplitude of Ko dependency. Since most of these parameters cannot be directly measured by experiment, these are searched for by applying an optimization technique, that is, by minimizing an objective function defined as a difference between a measured and a calculated waveform of action potentials in a cardiac myocyte. We employ the RSM as the optimization technique. In the RSM, a quadratic polynomial is used in general, and a mathematical technique is used to calculate the extreme points. Because our parameter space cannot be approximated by a single quadratic polynomial surface, we adopt a recursive subdivision technique and use the coefficient of multiple determination to representing a response surface in each subspace for a criteria of the subdivision. We confirmed the effectiveness of the proposed technique by searching for parameters which are determined in advance. PMID- 17270887 TI - Dynamic pathway modeling of sphingolipid metabolism. AB - We report our research results on computational metabolome study. The goal of this research is to extend the integrated experimental modeling methodologies in sphingolipid metabolism study to other complex biological process studies such as signal transduction or gene regulation. Another feature of This work is that the 3-D information representation enables the user orchestrate the simulated pathways in real time. PMID- 17270889 TI - Novel stepwise normalization method for two-channel cDNA microarrays. AB - Microarray experiments contain many sources of systematic errors. In order to extract biologically relevant information from microarray data, normalization needs to be applied to remove such variations. Although a number of normalization models have been proposed, it has not been well researched on how to select the most appropriate model with respect to the observed data. To tackle this problem, we propose A new stepwise within-slide normalization method, STEPNORM. It is a normalization framework that integrates various models of different complexities to sequentially detect and adjust systematic variations associated with spot intensities, print-tips, plates and two-dimensional spatial effects. We demonstrate the utility of STEPNORM on a set of well-studied cDNA microarray experiment. PMID- 17270888 TI - Automated characterization of gene expression patterns with an atlas of the mouse brain. AB - A spatio-temporal map of gene activity in the brain would be an important contribution to the understanding of brain development, disease, and function. Such a resource is now possible using high-throughput in situ hybridization, a method for transcriptome-wide acquisition of cellular resolution gene expression patterns in serial tissue sections. However, querying an enormous quantity of image data requires computational methods for describing and organizing gene expression patterns in a consistent manner. In addressing this, we have developed procedures for automated annotation of gene expression patterns in the postnatal mouse brain. PMID- 17270890 TI - An application of zero-suppressed binary decision diagrams to clustering analysis of DNA microarray data. AB - Clustering has been one of the most popular techniques to analyze gene expression data. The biclustering method is two-dimensional clustering of genes and experimental conditions to identify a group of genes that display a coherent behavior in some conditions. Although this method may provide additional insight overlooked by traditional clustering techniques, it is often computationally expensive to perform biclustering on practical gene expression data. In this work, we propose a novel biclustering technique that exploits the zero-suppressed binary decision diagrams (ZBDDs) to cope with such a computational challenge. The ZBDDs are a variant of the reduced ordered binary decision diagrams that have found a widespread use in optimization and verification of VLSI digital circuits. Our experimental results demonstrate that the ZBDDs can indeed extend the scalability of our biclustering algorithm substantially, thus enabling us to apply it to a wider spectrum of gene expression data. PMID- 17270891 TI - A new distance measurement for clustering time-course gene expression data. AB - The purpose of this paper is two-fold. First, a new distance measurement is proposed for temporal microarray gene expression data based on the angles of line segments in the curve of each individual gene expression profile. The hierarchical agglomerative clustering methods are used to incorporate this distance definition. Second, the assessment of the quality of clusterings obtained from the methods are provided by the use of the Davies-Bouldin validity index (DBI). We conclude that the DBI may not be an appropriate indicator for the quality assessment of clusters for time-course gene expression data. We provide an alternative DBI based on the normalized Pearson correlation for this purpose. PMID- 17270892 TI - A Bayesian approach to expression network component analysis. AB - A semiblind deconvolution method of analysis for gene expression data was proposed recently in a series of articles appeared in PNAS. We illustrate here how similar goals can be achieved in a Bayesian framework and how necessary information on the presence of binding sites can be obtained with Vocabulon, an algorithm based on a stochastic dictionary model. PMID- 17270893 TI - Network component analysis of Saccharamyces cerevisiae stress response. AB - A method, network component analysis, was developed for uncovering hidden regulatory signals from outputs of networked systems, when only partial knowledge of the underlying network topology is available. This method was successfully applied to microarray data of yeast Saccharamyces cerevisiae under various stress conditions. The activities of 96 transcription factors were determined, which differ significantly from their gene expression patterns. PMID- 17270894 TI - Discovering dynamic regulatory pathway by applying an auto regressive model to time series DNA microarray data. AB - In this paper we propose a novel method to extract dynamic regulatory pathways from time-series DNA microarray data. To this aim, first a specialized clustering technique is applied that utilizes the available heuristic information about the biological system to form the clusters. Then, an auto regressive (AR) model is applied to model the interactions among all genes and to predict the gene expressions for the next time steps. We tested the proposed method on the eukaryotic cell cycle data. The results indicate that the proposed method can successfully predict the dynamic pathway involved in this biological process. PMID- 17270895 TI - Genetic data acquirement, construction and analysis based on microarray technology. AB - Several novel microarray technology platforms to be applied to acquire both genetic and epigenetic data from biological systems have been developed. Genetic database and the related bioinformatics analytic tools are being constructed. Here, some on-going projects related to bioinformatics analysis based on the microarray technology, such as such as the high density microarray design, combinational analyses of the data based on microarrays for gene expressions, methylation of CG islands, trans-factor protein level and mutation detection, and the disease related SNPs in human genomes are presented. PMID- 17270896 TI - Association of beta-adrenoceptor single nucleotide polymorphisms with resting heart rate. AB - The association of beta-adrenoceptor (B-AR, including three subgroups: Beta1, Beta2 and Beta3) single nucleotide polymorphisms (SNP) with resting heart rate (RHR) were analyzed. RHR of 107 healthy subjects in the supine were detected by computerized system for 8 minutes. Genotyping SNPs of S/G49 and R/G389 of Beta1 AR and W/R64 of Beta3-AR in these subjects were by means of PCR-restriction fragment length polymorphism (PCR-RFLP) technique. Genotyping SNPs of R/G16 and Q/E27 of Beta1-adrenoceptor in these subjects were by means of allele specific primer-PCR (ASP-PCR) technique. It was found that there was no significant difference among RHRs corresponding above SNPs of B-AR, but the SNP of R/G389 of Beta1-AR, in which there was significant difference among RHRs (P<0.05). Either in the female individuals or in the male, those with Beta1-AR G/G389 genotype had the highest RHR. The females with R/R389 genotype had the lowest RHR, however, the males with R/G389 genotype had the lowest RHR. The RHR was not only associated with R/G389 polymorphism of Beta1-adrenoceptor gene significantly, but also was associated with gender in Chinese. PMID- 17270897 TI - Using multiagent system for gene expression classification. AB - Recent advances in microarray technology offer the ability to measure expression levels of thousands of genes simultaneously. Analysis of such data can help us identifying different clinical outcomes using only expressions of a few predictive genes. This paper presents an application of multiagent system to the analysis of gene expression data. Our goal is to find significant classification genes using simple classifiers that can be used by agents when exploring the gene expression database. We present our results on two well-known publicly available gene expression problems where we try to achieve the highest possible accuracy of classification using the smallest possible set of genes. PMID- 17270898 TI - A DNA-based pattern recognition technique for cancer detection. AB - The proper orthogonal decomposition (POD) technique (also known as the Karhunen Loeve transform) has been used as a model reduction tool for many applications in engineering and science. In principle, one begins with an ensemble of data, called snapshots, collected from an experiment or laboratory results. The POD technique is then used to produce a set of basis elements that can span the original snapshot collection using the fewest possible degrees of freedom. It is such capability that allows us to extract the representative characteristics of a cancer from a collection of DNA microarray samples known to be cancerous. The resulting few POD elements can be regarded as dominant cancerous patterns, which can be used to determine whether an arbitrary DNA microarray sample is cancerous. In our study, we consider two types of cancers, liver and bladder. DNA microarray data are downloaded from the Stanford Microarray Database. Our findings indicate that the POD method can successfully detect both cancer types, although our approach can be applied to other types of disease or cancer. PMID- 17270899 TI - Comparative study of microarray data for cancer research. AB - In comparison to traditional "single-gene" study method such as reverse transcriptase-polymerase chain reaction (RT-PCR), microarray technology can produce high-throughout gene expression data simultaneously. The advancement of this technology also presents a big challenge. In cancer research, the issue is how to identify the signature genes, or biomarkers associated with particular cancer to perform precise, objective and systematic cancer diagnosis and treatment. More specifically, the goal is how to accurately analyze and interpret the resulting large amount of gene expression data with relatively small patient sample size. As such, we have been developing a novel multischeme system that can derive optimal decision based on the best utilization of gene expression data features and clinical, and biological knowledge. In the paper, we are reporting the results of the first phase development of our novel system, to use unsupervised clustering methods to discover gene relationship and to use knowledge-based supervised classification to get highly accurate prediction in cancer diagnosis and prognosis study. This work sets up foundation for our next step drug target study. PMID- 17270900 TI - Protein secondary structure prediction with semi Markov HMMs. AB - Secondary structure prediction has been an essential task in determining the structure and function of the proteins. Prediction accuracy is improving every year towards the 88% estimated theoretical limit. There are two approaches for the secondary structure prediction. The first one, ab initio (single sequence) prediction does not use any homology information. The evolutionary information, if available, is used by the second approach to improve the prediction accuracy by a few percentages. In this paper, we address the problem of single sequence prediction by developing a semi Markov HMM, similar to the one proposed by Schmidler et al.. We introduce a better dependency model by considering the statistically significant amino acid correlation patterns at segment borders. Also, we propose an internal dependency model considering right to left dependencies without modifying the left to right HMM topology. In addition, we propose an iterative training method to better estimate the HMM parameters. Putting all these together, we obtained 1.5% improvement in three-state-per residue accuracy. PMID- 17270901 TI - Parallel protein secondary structure prediction based on neural networks. AB - Protein secondary structure prediction has a fundamental influence on today's bioinformatics research. In this work, binary and tertiary classifiers of protein secondary structure prediction are implemented on Denoeux belief neural network (DBNN) architecture. Hydrophobicity matrix, orthogonal matrix, BLOSUM62 and PSSM (position specific scoring matrix) are experimented separately as the encoding schemes for DBNN. The experimental results contribute to the design of new encoding schemes. New binary classifier for Helix versus not Helix ( approximately H) for DBNN produces prediction accuracy of 87% when PSSM is used for the input profile. The performance of DBNN binary classifier is comparable to other best prediction methods. The good test results for binary classifiers open a new approach for protein structure prediction with neural networks. Due to the time consuming task of training the neural networks, Pthread and OpenMP are employed to parallelize DBNN in the hyperthreading enabled Intel architecture. Speedup for 16 Pthreads is 4.9 and speedup for 16 OpenMP threads is 4 in the 4 processors shared memory architecture. Both speedup performance of OpenMP and Pthread is superior to that of other research. With the new parallel training algorithm, thousands of amino acids can be processed in reasonable amount of time. Our research also shows that hyperthreading technology for Intel architecture is efficient for parallel biological algorithms. PMID- 17270902 TI - A bipartite graph matching framework for finding correspondences between structural elements in two proteins. AB - A protein molecule consists one or more chains of amino acid sequences that fold into a complex three-dimensional structure. A protein's functions are often determined by its 3D structure, and so comparing the similarity of 3D structures between proteins is an important problem. To accomplish such comparison, one must align two proteins properly with rotation and translation in 3D space. Finding the correspondences between structural elements in the two proteins is the key step in many protein structure alignment algorithms. We introduce a new graph theoretic framework based on bipartite graph matching for finding sufficiently good correspondences. It is capable of providing both sequence-dependent and sequence-independent correspondences. It is a general framework for pair-wise matching of atoms, amino acids residues or secondary structure elements. PMID- 17270903 TI - Potential function of simplified protein models for discriminating native proteins from decoys: combining contact interaction and local sequence-dependent geometry. AB - An effective potential function is critical for protein structure prediction and folding simulation. For simplified models of proteins where coordinates of only Ca atoms need to be specified, an accurate potential function is important. Such a simplified model is essential for efficient search of conformational space. In this work, we present a formulation of potential function for simplified representations of protein structures. It is based on the combination of descriptors derived from residue-residue contact and sequence-dependent local geometry. The optimal weight coefficients for contact and local geometry is obtained through optimization by maximizing margins among native and decoy structures. The latter are generated by chain growth and by gapless threading. The performance of the potential function in blind test of discriminating native protein structures from decoys is evaluated using several benchmark decoy sets. This potential function have comparable or better performance than several residue-based potential functions that require in addition coordinates of side chain centers or coordinates of all side chain atoms. PMID- 17270904 TI - Computational prediction of binding hotspots. AB - We combine side-chain modeling, energy minimization and binding free energy calculation to predict point mutations with significant impacts on binding affinities (binding hotspots). Our method achieves high accuracy for two datasets (alanine-scanning mutations in ASEdb and 570 mutations on protease-inhibitor complexes). In particular, we can predict mutations that lead to improved binding with success. We discuss various factors that may contribute the prediction accuracy, including the amino acid to mutate to, and the position of the mutation. PMID- 17270905 TI - Linking molecular function and biological process terms in the ontology for gene expression data analysis. AB - The gene ontology (GO) contains three hierarchies that represent gene function based on categories of molecular function, biological process, and cellular component. However, additional knowledge about the mechanisms underlying gene function is buried in the GO term definitions and is not computationally accessible. We describe a process for adding new links to the GO between molecular function terms and the biological process terms that those molecular functions are involved in. These new links enable inference engines to reason about relationships between genes that have disparate molecular functions but participate in the same biological process. In particular, we demonstrate how these new links enable more effective automated analysis of gene expression data. PMID- 17270906 TI - Protein secondary structure prediction using neural network and simulated annealing algorithm. AB - Predicting the secondary structure of a protein (alpha-helix, beta-sheet, coil) is an important step towards elucidating its three dimensional structure, as well as its function. In this research we use a multilayer feed forward neural network for protein secondary structure prediction. The RS126 data set was used for training and testing the proposed neural network. We combined neural network and simulated annealing (SA) to further improve on the accuracy of protein secondary structure prediction. The results obtained show that by combining the neural network with SA technique improves the prediction accuracy in the range of 2-3%. PMID- 17270907 TI - PRISM: protein integration of sequence metrics. AB - PRISM is a comprehensive method for predicting protein sequence structure and function by providing a mechanism to combine information from numerous structure and function prediction tools into one comprehensive view. It uses an evidential reasoning calculus to combine information provided from multiple sources into a consensus solution. The output of PRISM is a comprehensive one stop shop report of all information about a given known or novel protein. PMID- 17270908 TI - Comparison of skin resistance between biological active points of left and right hands with various contact pressures. AB - Acupuncture has been a major part of primary healthcare in China for thousands of years. The acupuncture points or biological active points (BAP), also known as low-resistance spots or good electro-permeable points, have relative lower electric resistance than the surrounding tissues. There are many factors that can affect the measurement of the electric resistance of BAPs. We examined the relationship between the skin electric resistance at the BAPs of the left and the right hand with various contact pressures from 5 subjects. This preliminary study presented here shows there exists a bilateral symmetry of the skin resistance of the corresponding BAPs from the left and the right hands of all chosen subjects over a range of measuring pressure. PMID- 17270909 TI - Clustering protein-protein docking predictions. AB - We describe a clustering algorithm for improving protein-protein docking predictions. The algorithm was applied to two sets of predictions for 36 test cases, one set generated with a rigid-body docking algorithm ZDOCK, and the other set with ZDOCK followed by a refinement algorithm RDOCK, and consistent improvement was observed. PMID- 17270910 TI - Binding modes of two highly potent and nontoxic inhibitors of HIV-1 integrase. AB - The complex structures of Human Immunodeficiency Virus Type 1 (HIV-1) integrase binding two highly potent and nontoxic inhibitors, lithospermic acid (M/sub 5/22) and lithospermic acid B (M/sub 5/32), were obtained using docking calculations. Docking results provided detailed information of their binding modes. The binding sites of M/sub 5/22 and M/sub 5/32 were similar to the inhibitor 5-CITEP. The lowest docking energies for HIV-1 integrase binding M/sub 5/22 and M/sub 5/32 are in agreement with their corresponding lower IC/sub 50/ values. Our results on the chemical structure difference between M/sub 5/22 and M/sub 5/32 show that the carboxyl and hydroxyl groups on the side-chain of M/sub 5/32 are important chemical groups which could help to increase the effect against HIV-1 IN replication. PMID- 17270911 TI - A central partition of molecular conformational space. II. embedding 3D structures. AB - A combinatorial model of molecular conformational space that was previously developed, had the drawback that structures could not be properly embedded because it lacked explicit rotational symmetry. The problem can be circumvented by sorting the elementary 3D components of a molecular system into a finite set of classes that can be separately embedded. This also opens up the possibility of encoding the dynamical states into a graph structure. PMID- 17270912 TI - Knowledge-based algorithms for chemical structure and property analysis. AB - We have successfully developed 'rule-based' algorithms that efficiently perform sub- and exact-structure searching, as well as accurately describe the chemistry of small molecules. These algorithms use a simple and concise set of rules for information extraction from molecule files. This design is intended to reduce the computational time required for the process, while improving the accuracy in the tasks. The performances of these algorithms have been successfully validated with a wide range of small molecules. Our future goal is to combine these algorithms with our newly designed knowledge-based object database, such that their tasks can be automated with a high efficiency. PMID- 17270913 TI - Maximum a posteriori (MAP) estimator for polymerase chain reaction (PCR) processes. AB - A maximum a posteriori (MAP) estimator for polymerase chain reaction (PCR) assays is presented. The estimation relies on the replication efficiencies of the PCR assay and the observed end-point concentration of the PCR product at an arbitrary cycle. This derivation is carried out in view of the stochastic progression of the amplicons, and the assumption that the end-point concentrations for any particular initial value have a jointly Gaussian distribution. In addition, we provide an extension for the estimator which can be applied to various quantitative PCR assays. PMID- 17270914 TI - Domain specific languages for cellular interactions. AB - Bioinformatics is the application of computer science techniques to problems in biology, and this paper explores one such application with great potential: the modeling of life cycles of autonomous, intercommunicating cellular systems using domain-specific programming languages (DSLs). We illustrate this approach for the simple photo-synthetic bacterium R. Sphaeroides with a DSL called CellSys embedded in the programming language Haskell. PMID- 17270915 TI - Biodynamic modeling and simulation of multistage carcinogenesis. AB - We present a mathematical model of multistage carcinogenesis. The population genetic model is developed based on the reaction diffusion, logistic behavior, and Hollings Type II interactions between normal, benign, and premalignant mutant cells. Computer simulations are used to observe the behavior, stability, and traveling wave solution of the premalignant stage mutation as well as its survival under natural selection pressure. As a simple application of the model, the interaction between normal and tumor cells with one or two stages of mutation is analyzed. PMID- 17270916 TI - Computationally efficient cardiac bioelectricity models toward whole-heart simulation. AB - This work studies the characteristics of excitable cell mathematical models, with the goal of developing new insights and techniques in simulating the electrical behavior of the human heart. While very simple models of such behavior can be simulated at real-time or better speeds on powerful computing equipment, the use of realistic cell models or organ-magnitude cell networks make the simulations computationally infeasible. We present an examination of the FitzHugh-Nagumo model and its response to stimulus and, in order to move toward the goal of a full cardiac simulation, we present a method of optimizing single-cell calculations through local interpolation techniques. Additionally, we introduce a separate method of optimizing multicell simulations by tracking cellular activations. PMID- 17270917 TI - Bayesian networks of BI-RADStrade mark descriptors for breast lesion classification. AB - We investigated Bayesian network structure learning and probability estimation from mammographic feature data in order to classify breast lesions into different pathological categories. We compared the learned networks to naive Bayes classifiers, which are similar to the expert systems previously investigated for breast lesion classification. The learned network structures reflect the difference in the classification of biopsy outcome and the invasiveness of malignant lesions for breast masses and microcalcifications. The difference between masses and microcalcifications should be taken into consideration when interpreting systems for automatic pathological classification of breast lesions. The difference may also affect use of these systems for tasks such as estimating the sampling error of biopsy. PMID- 17270918 TI - The genetic profile of a tumor as a determinant of its response to radiotherapy: a computer simulation of two different radiotherapeutic schemes. AB - The aim of this paper is to present comparative results of a tumor response to radiotherapy model, concerning two different fractionation schemes and the insulin-like growth factor I receptor expression. A clinical case of glioblastoma multiforme is selected. The model parameters are appropriately adjusted according to the literature. The results of the simulation procedure are three dimensionally visualized and compared with clinical experience. PMID- 17270919 TI - Stochastic modeling and validation of growth saturation and radiotherapeutic response of multicellular tumor spheroids. AB - An advanced three-dimensional (3D) Monte Carlo simulation model of both the avascular development of multicellular tumor spheroids and their response to radiation therapy is presented. The model is based upon a number of fundamental biological principles such as the transition between the cell cycle phases, the diffusion of oxygen and nutrients and the cell survival probabilities following irradiation. Predicted histological structure and tumor growth rates evaluated for the case of EMT6/Ro spheroids have been shown to be in agreement with published experimental data. Furthermore, the underlying structure of the tumor spheroid as well as its response to irradiation satisfactorily agrees with laboratory experience. PMID- 17270920 TI - DNA sequence matching processor using FPGA and JAVA interface. AB - This study uses an FPGA to perform high-speed DNA sequence matching as an alternative to using general purpose computer CPUs. The FPGA is programmed using the Verilog HDL and interfaced using a graphical user interface programmed in JAVA. Design overviews and details for a small scale design are given as well as plans for larger scale expansion. Encouraging results of the small scale model currently in production are also provided. Results of a successful match and no match are shown. PMID- 17270921 TI - A software environment for simulators suitable for complex biological analysis. AB - In order to understand the function of biological elements and their interactions, computer analysis and simulation is an essential technique. For higher research efficiency, it is important to provide a system framework for constructing biological simulation systems that handle multiple phenomena. This paper proposes "DynaBioS", a comprehensive system framework for complex biological simulations. This framework consists of three main features, a component-based architecture, a customizable system operation, and an exchangeable model set. The system based on DynaBioS consists of a simulation core and system components. The system components are sub-simulators for individual functional factors and utility modules corresponding to specific information technologies. The simulation core manages and controls all components, in accordance with a simulation scenario and a simulation model. The DynaBioS makes it possible to implement different simulation systems by combining individual functional components, specific interactions and different simulation models. The versatility of DynaBioS is shown by two examples, a heart pumping simulator and a parameter optimization system for physiological models. PMID- 17270922 TI - Statistical assessment for mass-spec protein identification using peptide fingerprinting approach. AB - We derive and validate a novel statistical model for confidence assessment of protein identification results using peptide mass fingerprint data. We simulate the digestion of the proteins and compare each peptide mass with the input mass. We compute scores from this matching of peptide and compute the distribution of scores for all the proteins in the database. Based on the distribution, we can provide the expectation value for a protein match in the database. We conclude that, given the complexity and noise of the data, the best method for effective confidence matching is using one scoring scheme for matching and another scoring scheme for confidence assessment. PMID- 17270923 TI - Modeling protein tandem mass spectrometry data with an extended linear regression strategy. AB - Tandem mass spectrometry (MS/MS) has emerged as a cornerstone of proteomics owing in part to robust spectral interpretation algorithm. The intensity patterns presented in mass spectra are useful information for identification of peptides and proteins. However, widely used algorithms can not predicate the peak intensity patterns exactly. We have developed a systematic analytical approach based on a family of extended regression models, which permits routine, large scale protein expression profile modeling. By proving an important technical result that the regression coefficient vector is just the eigenvector corresponding to the least eigenvalue of a space transformed version of the original data, this extended regression problem can be reduced to a SVD decomposition problem, thus gain the robustness and efficiency. To evaluate the performance of our model, from 60,960 spectra, we chose 2,859 with high confidence, non redundant matches as training data, based on this specific problem, we derived some measurements of goodness of fit to show that our modeling method is reasonable. The issues of overfitting and underfitting are also discussed. This extended regression strategy therefore offers an effective and efficient framework for in-depth investigation of complex mammalian proteomes. PMID- 17270924 TI - Reducing the cost of protein identifications from mass spectrometry databases. AB - We present two techniques to improve the computational efficiency of protein discovery from mass spectrometry databases: noise filtering and hierarchical searching. Our approaches are orthogonal to existing algorithms and are based on the observation that typical mass spectrometry data contains a large amount of noise that can lead to wasteful computation. Our first improvement uses standard machine learning techniques with novel feature vectors derived from the mass spectra to identify and filter the noisy spectra. We demonstrate this approach results in computational gains of around 38% with less than 10% loss of peptides. Additionally we present a hierarchical searching scheme in which most samples are matched against a small database at low computational cost, leaving only a small number of samples to be searched against larger databases. Combining this scheme with the machine learning filters leads to a further performance improvement of 3%. PMID- 17270925 TI - Protein seer: a Web server for protein homology detection. AB - We present and evaluate a publicly available Web server which classifies protein sequences into SCOP 1.63 PDB95 structural superfamilies. The Website returns ranked lists of likely superfamilies and hence implicit structural predictions according to three computational techniques: BLAST, HMMER and a discriminative classifier SVM-BLOCKS. It is the first Website to provide predictions using SVM BLOCKS. In addition to the ranked lists, the Website displays alignment information and a Web services interface is also available for computationally intensive use. We conduct a large-scale evaluation which mimics the predictions returned by the Website. The study indicates that the site provides valid predictions and that SVM-BLOCKS approach can outperform BLAST and HMMER when sufficient examples are available to learn the SVM classifiers. PMID- 17270926 TI - Analysis and robot pipelined automation for SELDI-TOF mass spectrometry. AB - Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI or SELDI-TOF MS) with protein arrays has facilitated the discovery of disease-specific protein profiles in serum. As array technologies in bioinformatics and proteomics multiply the quantity of data being generated, more automated hardware and computational methods will become necessary in order to keep up. Robot automated sample preparation and analysis pipeline for proteomics (Raspap) in SELDI provides a solution from the lab bench to the desktop. In this approach, the entire processing of protein arrays is delegated to a robotics system and the bioinformatics automated pipeline (BAP) performs data mining after SELDI analysis. A key part of BAP is the creation of a journal-styled report in HTML (with text, embedded figures, and references) which can be automatically emailed back to the engineers/scientists for review. An object-oriented tree based structure allows for the derivation of conclusions about the data and comparison of multiple analyses within the generated report. Testing yielded improvement in the resulting assay coefficients of variation (CV) from 45.1% (when done manually) to 27.8% (P<0.001). A large biological dataset was also examined with the Raspap approach and consequent results are discussed. PMID- 17270927 TI - Modeling telehealth and telemedicine: a global geosociopolitical perspective. AB - Telehealth and telemedicine can encompass many applications including direct patient care, training, supervision, consultation, continuing education, and consumer health. The field uses an array of technology from the simplest telephony to advanced robotics. Therefore, it is important to work from a model in design or implementation. This rapidly changing and sometimes chaotic environment presents engineers with a unique opportunity to address the digital divide that is reflective of the geosociopolitical makeup of the world economy. The paper begins a developmental perspective of service delivery models currently used, likening the early years to a feudal system and the current time to a mosaic. After a brief look at the digital divide and the role of culture in technology, the paper concludes with application examples from projects around the world and suggests ways that model systems can be designed with various levels of technology. PMID- 17270928 TI - Improving heart failure care by using a telemedicine system. AB - Heart failure constitutes the most frequent and expensive hospital discharge diagnosis in the United States, costing annually over $10 billion. Optimal care requires an understanding of their illness, participating in clinical decisions, and frequent communication. Current surveillance is labor intensive and expensive. Follow-up is often inadequate, incomplete, and inconsistent. To address these problems, we developed an Internet-based telemedicine system, consisting of a secure server and database. Patients send or receive data to or from their care provider via the Internet. The system optimizes function and minimizes cost (all hardware is off the shelf and FDA approved). This paper describes our initial experience with this system. We are currently using this telemedicine system in a prospective, randomized clinical trial, comparing Class III or IV heart failure patients with standard care versus standard care plus telemedicine. PMID- 17270929 TI - A novel mobile telemedicine system for ambulance transport. Design and evaluation. AB - It is generally accepted that early and specialized pre-hospital patient treatment improves outcome in terms of mortality and morbidity, in emergency cases. The focus of this paper is to present the implementation and the evaluation of an ambulance located telemedicine system for pre-hospital patient treatment The primary emphasis is on the vital sign transmission from the accident site or the moving ambulance to the consultation site, using the GSM mobile telephony network. There, the experts evaluate the patient data, decides about the treatment protocol and provide directions to the ambulance's medical staff concerning on the patient handling until the arrival to the hospital. PMID- 17270930 TI - Using telehealth technology to improve the delivery of health services to people who are deaf. AB - The use of technology to access sign language interpreters from a remote location can have a significant impact on the timely access of such services for people who are deaf. The potential integration of such services is contingent on factors such as the availability of suitable equipment and the acceptance of the technological solution by people who are deaf, sign language interpreters and the health professionals. A system was assembled to address the needs of the users while maintaining focused on the requirement of the system being feasible such that it remains an option for small clinics and even medical offices. The technological solution was tested using simulated sessions involving people who are deaf, health professionals and sign language interpreters. The sessions simulated typical health conditions seen in hospital emergency rooms, medical clinics and doctor offices. Data collected from all participants indicate the technology proved to be acceptable in most simulated situations. PMID- 17270931 TI - Networking technology and health care in Eastern North Carolina. AB - Eastern North Carolina, roughly the northern half of the region east of Interstate 95, is a largely rural region that is in transition from a family farm related economy to small manufacturing and retirement communities. Poor education and the typical poverty-related diseases are endemic. It is served by one academic medical center, the Brody School of Medicine at East Carolina University, and a network of hospitals affiliated with the primary referral site, a 740-bed facility in Greenville. Broadband connectivity in the region is virtually absent outside the small urban centers; therefore, network-enhanced health care delivery is a challenge. ECU has maintained a successful and nationally recognized telemedicine center since 1994, averaging between 600 and 700 interactive consults per year, mostly between ECU physicians and institutional patients. Modernization of the center concept has begun with decentralization - placing videoconferencing equipment in our physicians' offices. With the development of a gigabit Ethernet network in the region new opportunities will soon be available to link off-campus physicians' offices to the medical center. Additional challenges await us in the arena of shared patient databases, home health monitoring, etc. Developments in these areas will be discussed. PMID- 17270932 TI - Establishing a rural telehealth project: the Wyoming network for telehealth. AB - The State of Wyoming, USA, is developing a series of demonstration projects on the use of telehealth technology to improve health care accessibility and quality in a frontier region. The Wyoming Network for Telehealth (WyNETTE) will focus on increasing the awareness and usage of technology for patient care, professional education, and informatics resources. The project objectives will include enhancing information access for practitioners and creating links between community health centers, public health offices, and state health officials. The need for this project was established through a number of community-oriented data collections, including a statewide survey of health care providers on the topic of using technology to improve delivery of health care survey in the state. The research showed a general lack of awareness of or experience with telehealth in the state. Nonetheless, there was considerable interest in developing partnerships to support a network of telehealth services. This paper will present the results of this data collection and how they are being used to guide the development of the WyNETTE project. PMID- 17270933 TI - Design of an interoperability framework in a regional healthcare system. AB - The integration of information systems represents one of the most urgent priorities of a regional healthcare authority in order to meet its clinical, organizational and managerial needs. Current practice shows that the most promising approach to achieve a regional healthcare information system (RHIS) is to use a health level 7 (HL7) message-based communication system implemented by an asynchronous common communication infrastructure between healthcare sites. The RHIS is a complete and integrated information system at a regional level that comprises all types of healthcare levels, that includes interoperability issues, that covers most of the needed components, and that is able to work efficiently in a secure wide area network to ensure data privacy and confidentiality. Another important feature of the proposed solution is that it creates an interoperability framework that can be replicated from one healthcare institution to another. In that sense, common interoperability messages can be used to interconnect heterogeneous information systems. In response to this strategy, more than 10 different consortiums have submitted proposals to the Greek government and the proposed interoperability' framework seems to be widely accepted as a solution to enhance information and communication technologies developments in the healthcare sector in Greece. PMID- 17270934 TI - Integration of monitoring devices in the e-Vital service. AB - The continuous treatment of chronic diseases such as heart diseases, pulmonary disease and diabetes, relies on the patient's self-monitoring. The rapid advance in the development of telemedicine systems and monitoring devices during last years gave several solutions in continuous patient telemonitoring. However, in most of the cases, these systems work with only one or a few types of medical devices and, thus, the variety of diseases they can monitor is rather limited. One of the main reasons for this is the fact that medical device manufacturers usually develop their own proprietary communication protocols and data format for each device. Most of the existing telemonitoring systems support communication with limited medical device types and depend on the manufacturer of them. We describe a modular and ambulatory telemedicine platform, the e-Vital platform, where different monitoring devices are being integrated in homecare and telemonitoring service chain, in order to increase patients' quality of life and their feeling of safety concerning their health. PMID- 17270935 TI - BioStream: a system architecture for real-time processing of physiological signals. AB - Continuous monitoring of physiological signals has the potential to greatly improve the quality of life of patients with chronic diseases. Recent advances in sensor technology make the capture of such signals possible. In this paper, we present BioStream, a real-time, and operator-based software solution for managing physiological sensor streams. It is built on top of a general-purpose stream processing software architecture. The system processes data using plug-in analysis components that can be easily composed into plans using a graphical programming environment. The architecture is scalable, allowing implementation on systems ranging from desktops to server farms. It guarantees real-time response and data persistence in a distributed environment. We apply this architecture to the problem of multipatient, real-time, physiological signal monitoring, analysis, indexing and visualization. PMID- 17270936 TI - Using handheld devices for real-time wireless teleconsultation. AB - Recent advances in the hardware of handheld devices, opened up the way for newer applications in the healthcare sector, and more specifically, in the teleconsultation field. Out of these devices, this paper focuses on the services that personal digital assistants and smartphones can provide to improve the speed, quality and ease of delivering a medical opinion from a distance and laying the ground for an all-wireless hospital. In that manner, PDAs were used to wirelessly support the viewing of digital imaging and communication in medicine (DICOM) images and to allow for mobile videoconferencing while within the hospital. Smartphones were also used to carry still images, multiframes and live video outside the hospital. Both of these applications aimed at increasing the mobility of the consultant while improving the healthcare service. PMID- 17270937 TI - Design of multimedia telemedicine system for inter-hospital consultation. AB - The telemedicine systems for the decision of patient transfer, and the direction of patient treatment through remote consultation are necessarily required for better patient care in emergency situation. In this paper, the prototype emergency telemedicine system has been designed and implemented. The unified integration of multimedia components, including full-quality video, vital sign signals, radiological images and video conferencing in a single computer, provides an efficient means to investigate the accurate status of emergency patient at the remote location. The software implementation of needed functionality without any externally attached hardware CODEC units enables the compact design with low cost, and ease of operation at the emergency room. Experimental tests at the local networks analyze the technical aspects of implemented systems, and optimize the parameters subjectively to run telemedicine systems with affordable error. Inter-hospital experiments demonstrate the possibility to be effectively used at emergency situation. PMID- 17270938 TI - TM-provider: a new communicatory model for telemedicine services support. AB - In this paper a new model for telemedicine service providers denoted as TM Provider is presented. The TM-Provider establishes two multilevel controllers for the fully administration of telemedicine sessions conduct. The communication between the controllers' levels is based on an advanced request-respond protocol that addresses the traffic of the messages and applies sophisticated security mechanisms for access and data protection issues. The proposed architecture and message-flow protocol synthesize a 'tool' for the designers and developers of telemedicine applications and provide them with an integrated architectural solution, independent of the various or advanced technologies and platforms that they intent to use. PMID- 17270939 TI - A front-end platform of the network-based intelligent home healthcare embedded system. AB - The aim of this article is to independently implement an indispensable front-end platform in a network-based intelligent home healthcare system. We propose to realize an ARM-cored structure embedded with muClinux system to integrate several kinds of medical measuring modules with our platform. Then we demonstrate the platform work cooperatively with all proposed and built -units. This most characteristic point of this platform lies in the implementation of the embedded expert system on the hardware basis. This kind of feature allows those aged and/or long-time patients to get medical diagnosis and advices at home, and, at the same time makes doctors work more effectively and pertinently. PMID- 17270940 TI - Modeling liver physiology: combining fractals, imaging and animation. AB - Physiological modeling of vascular and microvascular networks in several key human organ systems is critical for a deeper understanding of pharmacology and the effect of pharmacotherapies on disease. Like the lung and the kidney, the morphology of its vascular and microvascular system plays a major role in its functional capability. To understand liver function in absorption and metabolism of food and drugs, one must examine the morphology and physiology at both higher and lower level liver function. We have developed validated virtualized dynamic three dimensional (3D) models of liver secondary units and primary units by combining a number of different methods: three-dimensional rendering, fractals, and animation. We have simulated particle dynamics in the liver secondary unit. The resulting models are suitable for use in helping researchers easily visualize and gain intuition on results of in silico liver experiments. PMID- 17270941 TI - Virtual planning of multicatheter brachytherapy implants for accelerated partial breast irradiation. AB - Over the last decade, increasing numbers of breast cancer patients are being treated using interstitial radioactive implants (brachytherapy). Multiple catheters are placed in the breast using a free-hand or template-guided approach. The configuration of the catheters and their relation to the tumor target volume are crucial to effective treatment. Catheter insertion requires a high level of experience to produce an implant of excellent quality. Construction of optimal catheter configuration prior to the procedure (virtual planning) would reduce the dependence of implant quality on the skill of the physician. Currently available commercial planning systems do not allow for virtual planning. We have developed software which inputs the target anatomy for a prospective patient and matches it to a previously-delivered catheter configuration from an institutional implant library. The archived catheter arrangement is then customized to fit the new target volume. The user can actually explore the implications of variations in catheter number and spatial arrangement. This may significantly improve the quality of implants that would otherwise be designed strictly based on a physician's prior experience. In an academic environment, this new resource could lead to better, faster results in the treatment of breast cancer. PMID- 17270942 TI - Linking ontologies with three-dimensional models of anatomy to predict the effects of penetrating injuries. AB - Rapid diagnosis of penetrating injuries is essential to increased chance of survival. Geometric models representing anatomic structures could be useful, but such models generally contain only information about the relationships of points in space as well as display properties. We describe an approach to predicting the anatomic consequences of penetrating injury by creating a geometric model of anatomy that integrates biomechanical and anatomic knowledge. We created a geometric model of the heart from the Visible Human image data set. We linked this geometric model of anatomy with an ontology of descriptive anatomic knowledge. A hierarchy of abstract geometric objects was created that represents organs and organ parts. These geometric objects contain information about organ identity, composition, adjacency, and tissue biomechanical properties. This integrated model can support anatomic reasoning. Given a bullet trajectory and a parametric representation of a cone of tissue damage, we can use our model to predict the organs and organ parts that are injured. Our model is extensible, being able to incorporate future information, such as physiological implications of organ injuries. PMID- 17270943 TI - A novel navigation principle in computer-assisted surgery. AB - Novel methods of laser measurements and interventions in the framework of image guided surgery are presented. The first innovation concerns the basis of error propagation studies in registration chains from CT via OR navigator to the surgical laser tool holder. Here, we propose a holographic ground truth. The second innovation concerns a laser-based inherent sound-guidance principle for burr hole depth measurement. PMID- 17270944 TI - Content-based video coding for remote monitoring of neurosurgery. AB - Transmitting high-quality neurophysiology video via the Internet is a challenging problem in telemedicine. We propose a novel content-selective video data processing and compression method based on the Discrete Wavelet Transform (DWT). Our algorithm is adaptive to intraoperative monitoring video data and has a great scalability on real-time network bandwidth allocation. When compared with the general-purpose video compression methods, our method offers higher quality within the critical field of neurosurgery. PMID- 17270945 TI - Networked interaction therapy: relieving stress in memory-impaired people and their family members. AB - To relieve the stress in the lives of memory-impaired people and their family members, we propose the concept of Networked Interaction Therapy that connects them with community support group members via Internet by utilizing Internet communication, image understanding and sensory-interaction media technologies. To study their need and acceptance for our services, we made short video clips to illustrate our concept, and interviewed the care givers. Based on these studies, we also conducted the experiments with the low-fidelity mock-ups. PMID- 17270946 TI - Identification of Lenke spine deformity classification by simplified 3D spine model. AB - The 3D Bezier Curve is used to model the simplified 3D human spine for analyzing and classifying the scoliotic deformity. This 3D spine model is based on two orthogonal spinal radiographic images taken from coronal and sagittal planes. Superimposed on these two images, the 3D Bezier curves are fitted interactively onto the center of the spine from coronal and sagittal images. After the 3D Bezier Curve fitting, a series of simplified 3D vertebrae are implemented onto the 3D Bezier Curve proportional in size to its axis. The Lenke Classification system is applied to this 3D spine model. In order to identify the Lenke Classification for each individual spine model, the left side bending and right side bending images are added. Bending the 3D spine model interactively to the left and right determines the stiffness of the spinal deformity and whether the curves are structural. Thus the Lenke Classification could be determined. PMID- 17270947 TI - Personal recognition using head-top image for health-monitoring system in the home. AB - Automatic health-monitoring systems for the smart house are being developed for the elderly. An automatic health-monitoring system needs a way of personal recognition when two or more aged persons live together. We propose a personal recognition method based on the space spectrum of the head-top image. We examined 33 head-top images from eleven subjects and achieved a personal recognition rate of 86.4 percent. When one subject with thinning hair was excluded, the personal recognition rate was 90.0 percent in 30 head-top images from ten subjects. PMID- 17270948 TI - A home health monitoring system including intelligent reporting and alerts. AB - We describe the design and implementation of an intelligent reporting and alerts system that has been designed with a specific goal to address the needs of managing chronic and complex disease through the use of home telecare technology. Our approach has been to develop these tools using as far as possible, open standards. Clinical measurement data gathered using home telecare and stored in a relational database in XML format is extracted and converted into a Clinical Document Architecture (CDA) as defined by the Health Level 7 (HL7) organization. Data trends are presented to the clinician as simple graphs and summary statistics (means, standard deviations) over time for an individual patient. Clinicians may receive this data by display through a Web-interface or by email or faxed reports. A Ripple Down Rules (RDR) knowledge base supports more complex decision-making provided in the Alerts module. The RDR output is incorporated into the output reports as a textual statement, and/or a graphical highlighting of key parameters in the trends images and tables. Rule development and validation is part of ongoing research. PMID- 17270949 TI - An extensible framework for sharing clinical guidelines and services. AB - Accurate and descriptive information from clinical studies guides improvements in health care. Clinical guidelines established by authoritative medical organizations provide such information in a standard form for medical professionals' reference. Previous work on electronically sharing clinical guidelines focuses on the idea of building unified clinical terminologies and sharing resources through centralized data repositories. In this paper we propose a novel five-layer framework called the Extensible Clinical Guidelines and Services Sharing Architecture (ECGSSA). This framework provides for clinical guideline sharing among autonomous service providers over a distributed architecture. Requests for exchange of guidelines are disseminated through Web Services through a registry mechanism. Currently we have adopted the Guideline Interchange Format (GLIF) from InterMed as the representation format and use the Open Grid Services Architecture (OGSA) to attain virtual organization of shared guideline and service resources. This approach will allow more flexibility for medical professionals to exchange their practice guidelines in an effort to improve quality of health care. Also, it extends the possibility of solving clinic-related computational problems through collaborative sharing of analytical services. A sample scenario is presented to explain the application of ECGSSA in distributed task assignment and service matching in medical image processing. PMID- 17270950 TI - Application and evaluation of personal health information management system. AB - A web-based patient-centered personal health record (PHR), called the Personal Health Information Management System (PHIMS), has been developed and its usability has been evaluated in conjunction with a referral system, called the Facilitated Accurate Referral Management System (FARMS). To estimate the system requirements of PHIMS for wider clinical use, we have also studied PHIMS usage by analyzing server log files. A preliminary study showed 85% of survey respondents were satisfied with the usability and 94% were satisfied with the overall online referral process. The physicians were satisfied with the content of subjects' personal health information and found the information detailed enough to triage all requested referrals. PMID- 17270951 TI - Towards total knowledge management for healthcare: clinical and organizational considerations. AB - Knowledge Management (KM) has made a significant impact on the global healthcare sector. However, it is important to address the link between knowledge, information and engineering. Knowledge Engineering (KE) is often only a small part of a KM-based project, yet some KM practitioners favour wholly KE-biased Knowledge Management projects, disregarding a more necessary holistic stance. This paper analyses some current achievements in the KM field and provides a benchmark from which academics and practitioners can attempt to attain "Total Knowledge Management for Healthcare" (TKMh). PMID- 17270952 TI - An indexed atlas for content-based retrieval and analysis of mammograms. AB - We describe the development of an indexed atlas of digital mammograms to facilitate content-based retrieval and comparative analysis of mammograms for computer-aided diagnosis (CAD) of breast cancer. Specifically, the requirements and the design of the components of the indexed archival and retrieval system are examined. In order to facilitate search by categories, the mammograms in the atlas are indexed by case number, year of acquisition, category (normal, benign disease, and malignant disease that could be screen-detected or interval cancer), and the presence of signs of disease such as masses, calcifications, bilateral asymmetry, and architectural distortion. In the initial phase of the project, mammograms with masses have been indexed with objective diagnostic features related to their shape, edge definition, and texture. Interfaces to the atlas provide tools for selection and retrieval of cases by text-based or content-based indices. The system should assist radiologists and clinical specialists in CAD of breast cancer. PMID- 17270953 TI - The knowledge management landscape: implications for clinical knowledge management and practice. AB - The objective of this paper is to determine the future for Knowledge Management (KM) applications that focus on healthcare processes. This is achieved by tracing the evolution of KM by examining how different sectors have formulated industry specific KM applications, then discussing the key constraints that these sectors have faced whilst formulating industry specific KM applications. It then details how these constraints can impede the coming of age of KM applications for healthcare. The results of several case studies on the future of healthcare KM applications are presented. This paper thus attempts to contribute to the adoption of KM in healthcare by looking at how practitioners can overcome stumbling blocks in KM healthcare applications. PMID- 17270954 TI - Declarative algebra and continuous query language for biomedical stream processing in fetal monitoring system. AB - This paper presents the declarative algebra and continuous query language for fetal monitoring system MONAKO. Actually, architecture of this system is centralized. Recording, analyzing and visualization of data are carried out in the central unit. The new system will enable more efficient use of available resources and the construction of distributed structure. Presented example enables to define query based on data streams that makes the updated answers currently available. PMID- 17270955 TI - A database application to manage patients' data with a cochlear implant. AB - We have developed a database application software using Delphi 6 to manage patients' data with a cochlear implant. The software contains multiple functional modules used to record patients' medical and audiological evaluation, evaluation of hearing abilities, evaluation of speech and language status, evaluation of psychological status, rehabilitation and specific training, processor programming, follow-up and support, etc.. It also can generate various reports, convert patient's data to SPSS format for statistics purpose. The aim of the software is to help the decision-making for a cochlear implant, to develop a better pre-operative procedures that can predict how well a patient will perform with a cochlear implant, and also to reach a level by future research that will enable all implant patients to be "better-performing" patients. PMID- 17270956 TI - Transitional appearance-based motion tracking for real-time breast self examination supervision. AB - Despite much research and clinical trials, breast cancer still presents a serious threat of premature death to women. Early detection of the lumps in the breast is a key contributing factor to the successful treatment of this potentially fatal disease. Performing breast self-examination (BSE) in an accurate manner can assist a woman in detecting any abnormalities in her breasts, which may mark the onset of potential disease. This is also an essential tool used to enhance breast awareness. Using the hand, in a specific configuration, and palpating the entire breast in a certain movement pattern can optimise her feeling of the breast, In this paper we describe an intelligent automated algorithm for tracking the finger pads of a moving hand with the movement videos captured by a common web camera. The algorithm employs the principle of HCRA (hand configuration recognition algorithm) and its refinement through a simple but novel transitional appearance based model. A novel hand motion recognition algorithm (HMRA) is developed to recognise the motion pattern. Desirable tracking and recognition results have been achieved and the robustness of this algorithm is demonstrated in this paper. PMID- 17270957 TI - Support vector machine for determining dose of dialysis. AB - Calculation of dose of haemodialysis using blood-based modelling is subject to controversies as it is based on unrealistic assumptions. This paper proposes the use of dialysate-based modelling by SVMs to calculate the delivered dose of dialysis. The authors use the solute removal index (SRI), which is correlated to the amount of urea removed, for calculating the dose. The SVM model was trained to recognise the evolution of weight, blood urea nitrogen concentration and solute removal index with respect to time and then used to predict the solute removal index. When the estimated SRI values were compared to the actual SRI values determined by the standard method, the prediction errors were small. This paper is the first demonstration that SVM regression can predict delivered dose of haemodialysis with a clinically acceptable accuracy. The result is an effective technique that will offer the physician a better guide to the monitoring and prescription of haemodialysis therapy thereby reducing the mortality rate among patients. PMID- 17270958 TI - Computer aided interactive remote diagnosis using self-organizing maps. AB - A software tool has been developed to support the objective diagnosis of patients with Parkinson's Disease (PD). Patients completed hand exercises using a personal computer mouse and data has been gathered for further studies. We have analyzed different parameters and suggest using a particular parameter vector containing median and standard deviation values for tracking the daily changes in PD patients' status. Using the classification abilities of self-organizing feature maps (SOFM) we were able to provide support for the diagnostic process. PMID- 17270959 TI - Classification of lung data by sampling and support vector machine. AB - Developing a Computer-Assisted Detection (CAD) system for automatic detection of pulmonary nodules in thoracic CT is a highly challenging research area in the medical domain. It requires the application of state-of-the-art image processing and pattern recognition technologies. The object recognition and feature extraction phase of such a system generates a large number of data set. As there is normally a large quantity of non-nodule objects within this data set while the nodule objects are sparse, a Gaussian mixture model-based sampling method is used to reduce the non-nodule data and thus the classification complexity. The support vector machine, a classifier motivated from the statistical learning theory, is used in the pattern recognition stage of automatic pulmonary nodule detection. After the training process, only support vectors will be used in the classification process. As the support vector machine classifier gives the unique optimal solution, the experiment on the lung nodule data shows a fast and satisfactory classification rate. PMID- 17270960 TI - An input classification scheme for use in evidence-based dynamic recurrent neuro fuzzy prognosis. AB - This paper presents an input classification scheme used in an evidence-based dynamic recurrent neuro-fuzzy system for prognosis in rehabilitation. All external variables which may have an effect on the outcome of the rehabilitative process are classified into facts, contexts and interventions. Their effects on patients' physical and/or physiological states, which are estimated based on available evidence, are represented by fuzzy rules and/or non-linear models of physiologic processes. The outcomes of rehabilitation are defined as functions of those states. PMID- 17270961 TI - Predicting clinical outcomes for newborns using two artificial intelligence approaches. AB - Two different approaches, based on artificial neural networks (ANN) and fuzzy logic, were used to predict a number of outcomes of newborns: How they would be delivered, their 5 minute Apgar score, and neonatal mortality. The goal was to assess whether the methods would be comparable or whether they would perform differently for different outcomes. The results were comparable for Correct Classification Rate (CCR) and Specificity (true negative cases). Sensitivity (true positive cases) was slightly higher for the back-propagation feed-forward ANN than using the Fuzzy-Logic Classifier (FLC). Since this is one single database and a very large one, it is possible that the FLC would perform better than the ANN for very small databases, as shown by some of the co-authors in the past. The next step will be to test a small database with both methods to assess strengths and weaknesses with the intent to use both if needed with some medical data in the future. PMID- 17270962 TI - A new melanoma diagnosis active support system. AB - The aim of this paper is to present the operational performance of a new MDASS (Melanoma Diagnosis Active Support System) prototype able to distil optimal knowledge from acquired data to automatically capture and reliably discriminate and quantify the stage of disease evolution. Automated classification dermatoscopical parameters can be divided into two main classes: Size Descriptor (point size, local, and global) and Intrinsic Descriptor (morphological, geometrical, chromatic, others). Usually elementary geometric shape robust and effective characterization, invariant to environment and optical geometry transformations, on a rigorous mathematical level is a key and computational intensive problem. MDASS uses GEOGINE (GEOmetrical enGINE), a state-of-the-art OMG (Ontological Model Generator) based on n-D Tensor Moment Invariants for shape/texture effective description. MDASS main results show robust disease classification procedure with distillation of minimal reference grids for pathological cases and they ultimately achieve effective early diagnosis of melanocytic lesion. System results are validated by carefully designed experiments with certified clinical reference database. Overall system operational performance is presented. Finally, MDASS error analysis and computational complexity are addressed and discussed. PMID- 17270963 TI - Estimating the efficiency of medical diagnostic systems. AB - Lack of standardization in estimating the quality of diagnostic systems provides many possibilities in developing new methodologies. The paper deals with general method for determination of effectiveness of diagnostic systems in non-invasive diagnostics of thyroid. The result of presented methodology is a single number, which clearly depicts the quality of such a system with no need for further analysis. Together with the general design of such a system an overview of characteristics of a diagnostic system is described. PMID- 17270964 TI - Creating a text data-mining application for use in public health informatics. AB - Recent litigation and the Master Settlement Agreement of 1998 have made millions of tobacco industry internal documents available on the Internet (http://legacy.library.ucsf.edu). The Legacy interface, housed at the University of California, San Francisco, is based on a traditional information retrieval model in which documents are indexed and retrieved based on user-specified queries. One problem with the Legacy interface is information overload. In an attempt to ease this problem, we are developing a text-mining interface to enable exploratory analysis and discovery of information from collections of data. Users could uncover new patterns and concepts and thus text mining could result in searches that are targeted and specific, which would decrease information overload. In order to determine information needs, nine in-depth interviews with regular users of the Legacy interface were conducted. Results show that participants identified clustering as a useful tool in identifying and extracting key concepts and identified the need to recognize relationships between terms and concepts within the data. We encourage researchers who are developing text-mining interfaces to survey the users to learn what particular aspects of their research could be enhanced by text mining. PMID- 17270965 TI - SAGEDesktop: an environment for testing clinical practice guidelines. AB - Clinical practice guidelines have begun to appear in electronic form with the expectation that they will be used to provide automated clinical decision support. Systems capable of executing these clinical practice guidelines are emerging concurrently. A few research projects have developed guideline authoring tools that allow encoding electronic clinical practice guidelines. However, we are not aware of tools that allow testing of electronic clinical practice guidelines by their authors. We have developed a tool called SAGEDesktop for the testing of electronic clinical practice guidelines. SAGEDesktop does not require external infrastructure to carry out this testing. It includes: 1) an embedded guideline engine which can execute electronic clinical practice guidelines 2) functionality that emulates the capabilities of a clinical information system necessary for the execution of the guideline, and 3) terminology server functionality that encapsulates standard clinical terms. Coupled with an authoring tool, SAGEDesktop provides a complete development environment in which precise and robust electronic clinical practice guidelines can be encoded and tested. We describe the features of SAGEDesktop, narrate our vision of the tool's use, and discuss SAGEDesktop's strengths and weaknesses. PMID- 17270966 TI - Hand motion segmentation against skin colour background in breast awareness applications. AB - Skin colour modelling and classification play significant roles in face and hand detection, recognition and tracking. A hand is an essential tool used in breast self-examination, which needs to be detected and analysed during the process of breast palpation. However, the background of a woman's moving hand is her breast that has the same or similar colour as the hand. Additionally, colour images recorded by a web camera are strongly affected by the lighting or brightness conditions. Hence, it is a challenging task to segment and track the hand against the breast without utilising any artificial markers, such as coloured nail polish. In this paper, a two-dimensional Gaussian skin colour model is employed in a particular way to identify a breast but not a hand. First, an input image is transformed to YCbCr colour space, which is less sensitive to the lighting conditions and more tolerant of skin tone. The breast, thus detected by the Gaussian skin model, is used as the baseline or framework for the hand motion. Secondly, motion cues are used to segment the hand motion against the detected baseline. Desired segmentation results have been achieved and the robustness of this algorithm is demonstrated in this paper. PMID- 17270967 TI - Medical decision support system for diagnosis of soft tissue tumors based on distributed architecture. AB - This paper introduces a novel distributed decision support system to help radiologists in the diagnosis of soft tissue tumors (STT). Decision support systems are based on pattern recognition engines that discriminate between benign/malignant character and histological groups with a satisfactory estimated efficiency. This system is based on a distributed architecture with three specialized nodes: Radiologist Visual Interface, Information System and Decision Support Web-services. The visual interface is the radiologists and clinicians' point of access to local and remote STT registers, statistical analysis tools and distributed pattern recognition engines. A location-independent and multi platform system has been developed in order to connect hospitals and institutions to research useful tools in clinical and laboratory environments. The nodes maintenance and upgrade are automatically controlled by the architecture. This tool will be useful regarding the objective methodology to assist radiologist decision in a new case and will help the education of the new radiologists with no expertise in STT. PMID- 17270968 TI - Hereditary non-polyposis colorectal cancer risk assessment based on AI analysis of pedigree data. AB - Colorectal cancer (CRC) is one of the most common fatal cancers in developed countries and represents a significant public-health issue. About 3-5% of patients with CRC have hereditary non-polyposis colorectal cancer (HNPCC). Cancer morbidity and mortality can be reduced if early and intensive screening is pursued. But, despite advances in screening, population-wide genetic screening for HNPCC is not currently considered feasible due to its complexity and expense. If we can identify/assess the risk of a family having HNPCC, then only a fraction of the population will undergo intensive screening. This identification is currently performed by a genetic counsellor/physician who makes the decision based on some pre-defined criteria. The risk estimation by employing some mathematical methods, such as logistic regression, has also been reported. Our aim is to investigate the use of artificial intelligence techniques for genetic risk assessment. In this paper we summarize current knowledge on HNPCC and introduce the pedigree database used. Then we describe the system developed for HNPCC-risk assessment, which is based on analysing the pedigree data using self organizing maps. The experimental evaluation shows good classification results. PMID- 17270969 TI - Tracing medical images using multi-band watermarks. AB - The enforcement of Health Insurance Portability and Accountability Act (HIPAA) in April 2003 highlights the determination of federal government to protect the privacy of patients' records. However, we identify that there is a gap between current security solutions for the privacy protection of medical images and the HIPAA security guidelines: there is no measure to prevent and trace the authorized users who distribute medical images illegally. We evaluate the suitability of some most widely used watermarking techniques for tracing medical images, and demonstrate a need of developing new watermarking schemes that withstand standard medical image processing while maintaining high image quality for diagnostic purpose. We propose a multi-band watermarking scheme, that is robust to low pass filtering and high pass filtering, and yields high perceptual quality. We also present open research problems. PMID- 17270970 TI - Reversible watermarking for authentication of DICOM images. AB - We propose a watermarking scheme that can recover the original image from the watermarked one. The purpose is to verify the integrity and authenticity of DICOM images. We used 800x600x8 bits ultrasound (US) images in our experiment. SHA-256 of the whole image is embedded in the least significant bits of the RONI (Region of Non-Interest). If the image has not been altered, the watermark will be extracted and the original image will be recovered. SHA-256 of the recovered image will be compared with the extracted watermark for authentication. PMID- 17270971 TI - A multiple watermarking scheme applied to medical image management. AB - Digital watermarking is a recently emerged research area, which has the potential of providing alternative/complementary solutions for a number of issues relating to medical data management and distribution. The present paper aims to reveal the perspectives of digital watermarking in health information systems, and proposes a wavelet-based multiple watermarking scheme that addresses the issues of medical data protection, archiving, and retrieval, as well as of origin and data authentication. The scheme applies multiple watermarking in medical images, and embeds in them the physician's digital signature, patient's personal and examination data, keywords for image retrieval, and a reference watermark for the purpose of data integrity control. The experimental results demonstrate the efficiency and transparency of the watermarking scheme, which conforms to the strict limitations that apply to regions of diagnostic significance. PMID- 17270972 TI - Wavelet coding of volumetric medical images with high throughput and operability. AB - In this paper we propose a new 3D wavelet-based scalable lossless coding scheme for compression of volumetric medical images. Aiming to improve the productivity of radiologists and the cost-effectiveness of the system, we strive to achieve high decoder throughput, random access to coded data volume, progressive transmission, and high compression ratio in a balanced design approach. These desirable functionalities are realized by a modified 3D wavelet transform tailored to volumetric medical images. PMID- 17270973 TI - Efficient similarity retrieval for temporal shape sequences: a case study using cardiac MR images. AB - The spherical harmonics (SPHARM) approach has been used for the representation of shapes in many types of biomedical image data. We propose a SPHARM-based similarity comparison for shape sequences that allows fast similarity searches for dynamic objects and demonstrate it using 3D images of a beating heart. By using spherical harmonics to extract a small number of features that represent cardiac shape in each sequential state, we enable indexing and pruning of database entries with a multidimensional index tree (e.g. R*-tree) for fast retrieval. Our approach relies on obtaining selected landmarks to allow normalization within and between sequences. This framework is extensible to other application domains. PMID- 17270974 TI - libRASCH--a programming framework for transparent access to physiological signals. AB - For the analysis of physiological signals, such as ECG's, continuous blood pressure recordings etc., access to the raw signal data as well as to processed data is mandatory. Up to now, there is no computer program which allows access to raw and processed data independently from the file formats used. Thus, programs have to be adapted to each new file format. The aim of the programming library 'libRASCH', is to provide an interface which allows the access to physiological signals in a consistent way. libRASCH is written in C and runs under Linux and Windows. The source code of libRASCH is published under the GNU LGPL. A plugin mechanism for extension of the library was implemented. Support for some widely used data formats (e.g. European Data Format) is already available. To support a new file-format, only the corresponding plugin has to be written. Moreover all programs using this library, can handle the new format without further adjustments. For other programming languages than C (e.g. Perl, Python), interfaces are available. On the libRASCH website (http://www.librasch.org), the source code of libRASCH and further information's are available. PMID- 17270975 TI - Low-bandwidth telephony for urban and rural access to nursing services for survivors of stroke and their caregivers. AB - Trends related to rapidly aging populations nationally and internationally, combined with shortages in skilled health professionals and rising health care costs have necessitated efficient and cost-effective technologies for improved access to health care services. This paper discusses the use of low-bandwidth telephonic technology for providing nursing and counseling services to stroke caregivers in urban and rural areas and addresses factors that affect adoption and utilization of technologies for their intended use. Twenty-one subjects with recent stroke and their caregivers and five nurses were enrolled in the study. Seventy-two telehealth visits (i.e. tele-visits) were made to urban and rural locations using standard plain-old-telephone-service (POTS). Eighty-three percent of televists experienced first-time completion success at a bandwidth of 27.6+3 kbps. Over one-third (36%) of visits were unsolicited and initiated by caregivers using the protocol. Each tele-visit lasted approximately 20 minutes. Televisit sessions ranged from providing health care instruction for caregivers to stroke related education to caregiver counseling. Televists were widely accepted by stroke subjects and caregivers. Acceptance and utilization of telehealth services correlated with rapport between at-home users and nurses. PMID- 17270976 TI - A mobile-phone based telecare system for the elderly. AB - This study examined the use of telecommunications for home health care and described an alternative telemedicine framework. The framework aims to transmit small but sufficient amounts of data for daily monitoring of residential subjects' basic health status. We tested the remote monitoring of heart rate and respiration. The system was tested in real home-visit rehabilitation environments and was found to be useful both for the therapist and the patients in planning and evaluating daily rehabilitation training. PMID- 17270977 TI - Home health and home monitoring in rural and frontier counties: human factors in implementation. AB - An aging population, increases in chronic medical conditions, and the growth in healthcare expenditures have all combined to generate substantial interest in telehome care and home monitoring devices to address the health needs of our senior populations, especially in rural and frontier communities. Telehome care and home monitoring are attractive options to allow elderly rural residents to stay in their own homes and communities and receive necessary health care. The challenge in implementation is more on the human than the technological side of the equation. Human factors involve the primary provider, the home care agency personnel, the technical support available in rural areas, and the patient. Serious effort must go into making the patient comfortable, explaining the equipment, and building trust levels so that the monitoring equipment will be used. PMID- 17270978 TI - VTAMN--a smart clothe for ambulatory remote monitoring of physiological parameters and activity. AB - The prototype of a communicating underclothe for medical remote monitoring was realized. It delivers physiological information on the subject (Cardiac Frequency, Breathing Frequency, surface and mid-temperature) as well as the environment and activity parameters (ambient temperature, fall detection). It also enables the automatic data transfer on event, with the localization of the subject. PMID- 17270979 TI - Reconfigurable point-of-care systems designed with interoperability standards. AB - Interoperability standards, if properly applied to medical system design, have the potential to decrease the cost of point-of-care monitoring systems while better matching systems to patient needs. This paper presents a brief editorial overview of future monitoring environments, followed by a short listing of smart home and wearable-device efforts. This is followed by a summary of recent efforts in the Medical Component Design Laboratory at Kansas State University to address interoperability issues in point-of-care systems by incorporating the Bluetooth Host Controller Interface, the IEEE 1073 Medical Information Bus, and Health Level 7 (HL7) into a monitoring system that hosts wearable or nearby wireless devices. This wireless demonstration system includes a wearable electrocardiogram, wearable pulse oximeter, wearable data logger, weight scale, and LabVIEW base station. Data are exchanged between local and remote MySQL databases using the HL7 standard for medical information exchange. PMID- 17270980 TI - Status of mobile computing in health care: an evidence study. AB - Information technology (IT) has played an impacting role in helping healthcare professionals increasingly recognize the value of IT in clinical medicine, disease management, treatment strategies and other related areas. Of the numerous IT applications currently pursued, the use of telemedicine is a major force in addressing the healthcare delivery issues. As evidenced by a number of studies, telemedicine has come to play a significant mode of delivery and treatment, especially in the remote rural areas. Despite the growing interest, the R&D advances and the vast number of telemedicine applications currently ongoing, there still seem to be only a few quantitative studies characterizing the economic aspects of telemedicine and how cost-effective such solutions are. Of particular interest to the healthcare community is the effectiveness of the emerging mobile communications in telemedicine especially in home healthcare environment. In this paper we report on a profile of the current status of the use of mobile devices based on an extensive literature search of 213 articles. In particular we have focused our research on reports of the cost effectiveness of mobile telemedicine applications with respect to improved quality of care and medical error reduction. Preliminary results are reported in the paper, with an extended discussion to be provided in the final conference presentation, based on outcomes obtained from a more robust data analysis. PMID- 17270981 TI - A wearable device for a fully automated in-hospital staff and patient identification. AB - In the health care context, devices for automated staff / patient identification provide multiple benefits, including error reduction in drug administration, an easier and faster use of the Electronic Health Record, enhanced security and control features when accessing confidential data, etc. Current identification systems (e.g. smartcards, bar codes) are not completely seamless to users and require mechanical operations that sometimes are difficult to perform for impaired subjects. Emerging wireless RFID technologies are encouraging, but cannot still be introduced in health care environments due to their electromagnetic emissions and the need for large size antenna to operate at reasonable distances. The present work describes a prototype of wearable device for automated staff and patient identification which is small in size and complies with the in-hospital electromagnetic requirements. This prototype also implements an anti-counterfeit option. Its experimental application allowed the introduction of some security functions for confidential data management. PMID- 17270982 TI - A mobile teletrauma system for rural trauma care. AB - This paper introduces a cost-effective, portable teletrauma system that assists the health care centers in providing pre-hospital trauma care to rural population. Simultaneous transmission of a patient's video, medical images, and ECG signals, which is required throughout the prehospital procedure, is demonstrated over commercially available, low-bandwidth, wireless cellular data service using transmission technologies such as CDMA. Moreover, the physician can remotely control the information sent from the patient side. Such a technology will allow a trauma specialist to be virtually present at the remote location and participate in pre-hospital care, which improves the quality of trauma care and can potentially reduce mortality and morbidity. PMID- 17270983 TI - Design considerations and implementation of a cost-effective, portable remote monitoring unit using 3G wireless data networks. AB - This paper describes the design and implementation of a light-weight, autonomous, patient-centric, portable medical unit that allows for anytime/anywhere monitoring and can find use in many monitoring scenarios like home-care, hospital wards, emergency help and disaster relief. The proposed unit called "TelePatient" achieves portability by exploiting a PDA and allows mobility through the use of cellular technology, enabling complete ubiquity. The design is based on open standards and is cost-effective. We incorporate transcoding software to fit data to limited bandwidth, as well as conserve energy on the power constrained PDA. We validate our design over real network 3G CDMA conditions and also test its use over WLAN802.11b, which can together cover a number of Telemedicine scenarios. PMID- 17270984 TI - DI@L-log by design: an integrated tele-care communication infrastructure. AB - A spoken dialogue system for the acquisition of type 2 diabetes mellitus (T2DM) home monitored patient data known as DI@L-log is presented. The purpose of the system is to collect weight, blood sugar and blood pressure readings from a cohort of hypertensive T2DM patients on a weekly basis using their home telephone. The recent voice-data convergence affords an arguably improved means for doctors to track patient health states at a distance in order to provide health institutions with more frequent and accurate patient profiles. Our system architecture integrates VoiceXML and the standard PSTN, with a Pan-European open source for hosting Internet telephony applications. This paper reports on recent developments in the design of DI@L-log, which aims to serve as a communication intervention that disparages the traditional paper logbook used to document readings by the patient. PMID- 17270985 TI - The potential of a store and forward tele-behavioral platform for effective treatment and research of autism. AB - This paper describes the justification and the design principles of a behavioral medicine store & forward telemedicine platform to facilitate the capturing and communication of spontaneous patient behaviors for the improved evaluation, diagnosis and ongoing treatment of people with autism. This Tele-Behavioral Health platform will allow families and other caregivers to readily capture spontaneous patient behaviors for subsequent evaluation by appropriate medical specialists. A unique feature of the system is its capability to archive and index the data for access as well as comparison over time by clinicians and other researchers. Such a system may serve as a precursor to further advances in other health information technology applications leading to more effective treatment and a better understanding of this disability. PMID- 17270986 TI - A low-cost framework for individualized interactive telerehabilitation. AB - In this paper we examine the issues pertaining to development of a low-cost telerehabilitation framework for upper-limb dysfunction, that is suitable for deployment in patients' homes. We use the example of a Virtual Driving Environment (VDE) to present the overall architecture and discuss issues of: (i) quantitative data-acquisition using commercial-off-the-shelf gaming devices; (ii) model-based parametric data transmission/playback; and (iii) parametric biomechanical identification and data reduction; to support individualization within the telerehabilitation regimen. PMID- 17270987 TI - Wearable devices for emerging healthcare applications. AB - Today's quality of life is supported by medical capabilities that have not been available years ago. These capabilities are not limited to disease treatment only, indeed there has been a paradigm shift to disease prevention and monitoring. Especially continuous monitoring of patients or even of people who are only interested in their health has received increasing interest. Thus, the need and the potential to miniaturize lab-scale monitoring devices have inspired many research projects and start-up companies to create new or to miniaturize medical applications. Challenges in this area comprise low-power/power saving design to extend battery life and to reduce the size of the battery itself. This is followed by size/height/weight reductions to meet user expectations of being "wearable", biocompatibility of all outer housings, and the final assembly concept. Instead of using a sequential design approach, the complexity mandates to handle all aspects concurrently as early as possible in the design phase. Already during this design phase HDP (high-density packaging) technologies help to meet the size requirements without sacrificing too much flexibility and violating time/cost constraints. This paper will present two miniaturization design strategies, considerations and solutions for two novel medical applications in the health monitoring area. PMID- 17270988 TI - ACTIDOM--a microsystem based on MEMS for activity monitoring of the frail elderly in their daily life. AB - A "ambulatory activity recorder" was developed, with 3 accelerometers and 3 magnetometers, to detect and qualify the elementary activities of a person, such as walking and transfers. The signal processing is explained, along with the preliminary results obtained on young and older healthy subjects. This work open the way to continuous and automatic monitoring of the level of mobility. PMID- 17270989 TI - Realization of an e-health system to perceive emergency situations. AB - Emergency situations can occur anywhere and anytime in daily life. In the paper, we present an e-health system to perceive emergency situations of a patient. Using a wearable shirt (BioShirt) and a personal monitoring system (PBM), we obtain the body signals of a user. The monitoring system collects and transmits the vital signs to a personal digital assistant (PDA) via a BlueTooth communication module. To detect emergency from the received data, a simple detection algorithm is performed in the PDA. And the PDA forwards the data to an e-health central monitoring room (ECMR), if necessary. In the ECMR, several operators supervise the registered users based on incoming body signals from each user's device. If an automatic decision-making algorithm generates an emergency alarm, the operators try to contact the corresponding patient and recognize his status. Ultimately if they decide that the patient is an urgent situation, they give phone calls and messages to the emergency center and the patient's medical attendant immediately. PMID- 17270990 TI - A communication platform for diabetes surveillance. AB - Diabetes mellitus is a common and precarious chronic disease, which affects cellular metabolism and energy production. The condition is divided into types I and II; the most common form is type II diabetes, which is an adult-onset disease. Blood glucose testing is crucial to diabetes control, and it is effective in reducing the risk of complications and improving life quality. Unfortunately, both elderly patients and their caregivers find it difficult to monitor glucose levels long term. This study developed a communication platform for diabetes surveillance. The developed system prompts diabetics to measure their blood glucose regularly at home, and provides remote care persons with complete information about the patient's measurement. This aids in the improvement in diabetes control, thereby increasing the social activities and life quality of diabetics. PMID- 17270991 TI - A mobile phone-based safety support system for wandering elderly persons. AB - A new safety support system has been developed to detect and transmit notification of a wandering elderly person's location. The system employs a low transmitting power mobile phone (PHS) and a personal computer (PC). The PHS is carried with the elderly person as a pendant. The PHS location is identified within 100 m from the receiving antenna ID. Therefore, the system can detect whether the wandering elderly person is in or out of their home. When the wandering elderly person is away from home, the system automatically informs the caregiver via voice mode and sends the wandering elderly person's location map by e-mail. PMID- 17270992 TI - Design of a wearable device for ECG continuous monitoring using wireless technology. AB - This project focuses on the design and implementation of an intelligent wearable device for ECG continuous acquisition and transmission to some remote gateway using Bluetooth technology. The acquisition device has been designed for having very low power consumption and reduced size. The Analog Devices' ADuC831 Micro Converter for achieving the analog to digital conversion and the CSR's BlueCore2 chip for the Bluetooth transmission are the core of the device. The designed device is an important component of a complete prototype for remote ECG continuous monitoring of patients with diverse cardiac diseases. PMID- 17270993 TI - SCIENT--smart configurable infrastructure for next-generation telemonitoring. AB - The main contribution of this paper is the design and development of a middleware platform to build Next Generation Telemonitoring applications. The framework, called "SCIENT", is smart, providing adaptability to operating environments as a first class feature and is configurable, allowing it to be tailored to different medical applications. SCIENT aims to annul the repetitive work in designing Telemonitoring applications and provides a platform for rapid prototyping, considerably lowering costs. Extendibility, modularity, and evolvability are other important considerations of the design. We present a proof-of-concept implementation of SCIENT and build two applications using the framework to demonstrate the feasibility of our solution. PMID- 17270994 TI - Java-based browsing, visualization and processing of heterogeneous medical data from remote repositories. AB - The actual development of distributed information technologies and Java programming enables employing them also in the medical arena to support the retrieval, integration and evaluation of heterogeneous data and multimodal images in a web browser environment. With this aim, we used them to implement a client server architecture based on software agents. The client side is a Java applet running in a web browser and providing a friendly medical user interface to browse and visualize different patient and medical test data, integrating them properly. The server side manages secure connections and queries to heterogeneous remote databases and file systems containing patient personal and clinical data. Based on the Java Advanced Imaging API, processing and analysis tools were developed to support the evaluation of remotely retrieved bioimages through the quantification of their features in different regions of interest. The Java platform-independence allows the centralized management of the implemented prototype and its deployment to each site where an intranet or internet connection is available. Giving healthcare providers effective support for comprehensively browsing, visualizing and evaluating medical images and records located in different remote repositories, the developed prototype can represent an important aid in providing more efficient diagnoses and medical treatments. PMID- 17270995 TI - Design of a web-based health promotion system and its practical implementation for cycle ergometer exercise. AB - Health promotion is a very active topic in recent years. Most people want to exercise regularly, but there are various obstacles to keep staying motivated in their busy life today. In this paper, we propose a system design on a proven enterprise architecture that aims to support in constituting a comprehensive infrastructure for a wellness exercise environment. The design extends normal health promotion model to address cost-efficient and forward-looking for future health industry. Moreover, web-based technology has been widely adopted to implement a platform-nature solution in a heterogeneous computing environment based on the Internet. In particular, a Self-describing strategy for effectively developing and deploying exercise programs has been originally proposed and contrived. By applying the design to cycle ergometer exercise, we presented a practical exercise system realizing easy-to-use operation interfaces on a web browser. The web-based cycle ergometer exercise system was proved to be workable in our feasibility experiments. PMID- 17270996 TI - Towards a web services infrastructure for perinatal, obstetrical, and neonatal clinical decision support. AB - This paper presents the design of a unifying infrastructure for clinical decision support systems (CDSSs) and medical data relating to the perinatal life cycle. The diverse CDSSs designed for deployment within the perinatal life cycle to improve care, such as Artificial Neural Networks and Case-Based Reasoners, are integrated using the eXtended Markup Language (XML) and are subsequently offered as a secure web service. These web services are accessible from anywhere within the hospital information system and from remote authorized sites. The goal of such an infrastructure is to provide integrated CDSS processing in a complex distributed environment, in order to support real-time physician decision-making. This design provides a novel web services infrastructure implementation and offers a strong case study for deploying and evaluating the web services paradigm within a health care environment. PMID- 17270997 TI - HL7-compliant healthcare information system for home monitoring. AB - A secure, home-to-remote database communication hierarchy using Health Level Seven (HL7) has been developed. Measurements acquired from the patient via a wireless, wearable monitoring system are inserted into a local database using LabVIEW. Periodically, the HL7 client securely updates the remote database with information from the local database. HL7 communications are performed by Interfaceware's Chameleon software. Using Chameleon's flexible interface, doctors and researchers may access these patient data securely, confidentially, and remotely. PMID- 17270998 TI - "On-demand" access to a multi-purpose collection of best practice standards. AB - On-demand" information has been chosen by clinicians as one of their preferred modes of interaction with computers when in need of information about evidence based practices. However, most of the clinicians' information needs remain unmet, especially due to a lack of easy access to resources that are able to satisfy these needs in a timely manner. We present three scenarios indicating opportunities for a clinical information system to present interdisciplinary standards at the point-of-care. In each scenario, we highlight the importance of context of use and the opportunities offered by the clinical workflow for providing access to relevant "on-demand" information. We also present an XML model for structuring non-physician interdisciplinary standards, in an effort to fulfill the requirements exposed by the three scenarios. PMID- 17270999 TI - Integrating clinical trial data for decision making via web services. AB - Conducting clinical trials involves processing a large amount of data generated at different stages of the studies. Such data come from a variety of sources and numerous decisions are made based upon the data to ensure the quality and integrity of the study. The multiplicity of data source poses challenges in making decisions in a timely manner. We designed a solution, called Clinical Trial Console, using Web services, an open standard for programmatic interfaces over the internet based upon XML and other internet protocols, to provide an integrated view of clinical trial data that facilitates prompt decision making. PMID- 17271000 TI - The knowledge authoring tool: an XML-based knowledge acquisition environment. AB - As part of an enterprise effort to develop new clinical information systems at Intermountain Health Care, we are developing a Knowledge Authoring Tool that facilitates the development of medical knowledge. At present, users of the application can compose order sets and other clinical knowledge documents based upon XML schemas. The flexible nature of the application allows for the authoring of new types of documents once an XML schema and accompanying web form have been developed and stored in a shared repository. The need for a knowledge acquisition tool stems largely from the desire for medical practitioners to be able to write their own content for clinical use. We hypothesize that knowledge content for clinical use can be successfully implemented around XML-based document frameworks containing structured and coded knowledge. PMID- 17271001 TI - Application of HL7 in a collaborative healthcare information system. AB - This paper presents our application of Health Level Seven (HL7) standard in a collaborative healthcare information system (HIS). Originally, we have used HL7 message events to flow among HIS systems. Later on, we found that the message interface management become a nightmare for system engineers. Recently, we extract the spirit of HL7 standard to create an alterative HL7 usage over the web services, and reorganize our traditional programmer team into a software collaborative team (SCT) to manage the project schedules effectively. Gradually, this new methodology had already been accepted by most of our system engineers. Moreover, the application of this methodology at National Taiwan University Hospital (NTUH) has shown that it can decrease the HIS system development cost. PMID- 17271002 TI - Teleconsultations using content-based retrieval of parametric images. AB - The problem of medical teleconsultations with intelligent computer system rather than with a human expert is analyzed. System for content-based retrieval of images is described and presented as a use case of a passive teleconsultation. Selected features, crucial for retrieval quality, are introduced including: synthesis of parametric images, regions of interest detection and extraction, definition of content-based features, generation of descriptors, query algebra, system architecture and performance. Additionally, electronic business pattern is proposed to generalize teleconsultation services like content-based retrieval systems. PMID- 17271003 TI - A system for ubiquitous health monitoring in the bedroom via a Bluetooth network and wireless LAN. AB - Advances in information technology have enabled ubiquitous health monitoring at home, which is particularly useful for patients, who have to live alone. We have focused on the automatic and unobtrusive measurement of biomedical signals and activities of patients. We have constructed wireless communication networks in order to transfer data. The networks consist of Bluetooth and Wireless Local Area Network (WLAN). In this paper, we present the concept of a ubiquitous-Bedroom (u Bedroom) which is a part of a ubiquitous-House (u-House) and we present our systems for ubiquitous health monitoring. PMID- 17271004 TI - Multi-channel measurement of photo-plethysmography and evaluation for the optimal site of a thigh in a toilet. AB - It is hard to obtain the physiological signals from the thigh. In this study, we used multi-channel photo-plethysmography systems and monitored the signals to know the optimal sites. For the reliability, 8 subjects were participated in the study, and the estimations of probability about their obtained signals were done. With bluetooth technique, we made a remote monitoring don Finally, we chose the candidate sites for the optimal sites and our study will be continued to monitoring the noninvasive and nonconscious physiological signals with this information. PMID- 17271005 TI - Development of "MobileAudiometer" for screening using mobile phones. AB - As we age, the functions of our body and sensory organs deteriorate. Diagnosis of hearing problems tends to be delayed and people put off wearing hearing aids as they are not aware of the deterioration and get used to paying little attention to their hearing difficulty. Adaptation of sound is necessary because sound quality perceived with hearing aids differs from that of normal sound. Detection of hearing problems at an earlier stage is important. An audiometer that can screen persons with hearing loss easily at an early stage is necessary. In this paper, a prototype of the simple audiometer as the audiometer classified into type 4 for screening/monitoring purposes regulated in IEC standards, proposed in the previous research, is developed on the mobile phone by Java application program and ringing tones of mobile phones. The functions and performance of the prototype are verified along IEC standards. PMID- 17271006 TI - Experiences using WinCE PocketPCs as computation and data acquisition platforms for ambulatory telemonitoring. AB - Using a WinCE PocketPC as a central controller and computational platform to acquire and process medical data in an ambulatory telemonitoring environment seems to be a reasonable design decision. This paper summarizes the advantages and disadvantages of such a platform based upon recent experiences with wireless telemonitoring in large animals. PMID- 17271007 TI - Use of M3S for mobile/local controls over a remote/fixed environment. AB - The M3S (Multiple Master Multiple Slave) is an intelligent transmission system for the disabled. This integrated system combines technical aids for mobility, manipulation, environment control and communication. However, signals must be transmitted by a RF (Radio Frequency) module to overcome critical limitations of the CAN Bus (e.g. length). Appliances in different rooms are attached to different "remote" M3S Busses, while the user's "local" M3S Bus controls these remote links by manipulating all output devices on the remote end with input devices on the local end. Signals may also be transferred singly through remote M3S Busses, allowing the neighborhood remote Busses to interface between origin and destination. PMID- 17271008 TI - A novel communications network for the provision of medical care in disaster and emergency situations. AB - We have designed and developed a novel data communications network targeted at the provision of Emergency Medical Care in disaster situations over wide areas. The network nodes can transmit essential biosignals and in addition, support video and diagnostic quality sound (auscultation) broadcasting for teleconsultation purposes, by using a variety of wireless transports. The medical data acquisition stations are networked dynamically and on demand, with no requirement for an existing communications infrastructure at the disaster sites. The network design allows for limited transmitting station mobility and support for software-based Voice over IP during station roaming. Initial test results, following the hardware and software integration, indicate that the chosen network design meets specifications, and a full-scale field test, utilizing a large number of wireless stations operating under realistic conditions is to take place. PMID- 17271009 TI - Development of wireless blood glucose meter and diabetes self-management system. AB - Diabetes is a metabolic disorder that is characterized by high blood glucose and either insufficient or ineffective insulin. Blood glucose measurement is crucial to diabetes control, and it is effective in reducing the risk of complications and improving life quality. Unfortunately, both elderly patients and their caregivers find it difficult to monitor glucose levels long term. This study attempts to develop an intelligent maintenance system for home glucose measurement, wireless data transformation, and information analysis. The developed system prompts diabetics to measure their blood glucose regularly at home, and provides remote caregivers with complete patient information for diagnosis and tracking. This aids in the improvement in diabetes control, thereby increasing the social activities and life quality of diabetics. PMID- 17271010 TI - Mobile telemedicine system for home care and patient monitoring. AB - Home care services are growing up in the past years. Contemplating the patient/family pair, it represents a solution to the medical problems of the modern life. With the social trends, the senior population has been increasing in the last years. However, as living is more stressful than ever, there are more cases of chronic diseases. The difficulties of transport in the big cities and the scarcity of hospital streambeds turn the home care an attractive solution. However, its routines can be switched by telemedicine. This paper describes the implementation of a telemedicine system for patient monitoring using mobile telephony. The major aspect about this application is its generality, which allows the use of any patient monitor with a RS-232 interface. The system proved to be quick and reliable. Therefore, it represents an applicable solution to telehomecare. PMID- 17271011 TI - TeleHealth: operational issues to consider. AB - Recent developments in the telecommunications and the information technology fields hold the promise of improved access to and better utilization of an integrated health care related resources. In addition, to these developments, the deployment of interactive distant training programs offer an opportunity to decrease the knowledge gap between the leading academic medical centers where new medical expertise is continuously being discovered and remote health care practitioners who find themselves pressed to deliver quality care that meets the needs of their communities in a competitive environment of limited resources. PMID- 17271012 TI - The telemedicine and teleconsultation system application in clinical medicine. AB - Telemedicine and teleconsultation are the application and development of the telecommunication networks. Health experts can solve problems by using the electronic and communication technologies without distance limitation. In this study, we try to develop the telemedicine and teleconsultation system between local site and consulting expert site. Two applications of this system in clinical medicine are discussed. The system at each site has a workstation including a cable modem or ADSL connection, a monitor, a web camera, speakers, a microphone for communication, and NetMeeting application software. The first application in this study is to develop a school-based intervention program by using this system for high-risk school-age children in one of the earthquake struck areas. The preliminary result of this study is that the telemedicine and teleconsultation system is more effective than traditional consultation and supervision. Moreover, we can apply this system in training local volunteers, educators, and welfare workers. Meanwhile, we can save lots of cost and time since we don't need to travel between the local site and the expert site. In the end of this study, the second application of this system in SARS case treatment was also discussed. PMID- 17271013 TI - Transmission of digital electrocardiogram (ECG) via modem connection in southern Brazil. AB - A lack of cardiologists in remote areas can delay the diagnosis and the adequate management of cardiovascular emergencies. The digital tele-ECG system (DES) allows electronic data transmission to, and interpretation by, a remote cardiologist. An urban and a rural hospital in Sao Lourenco do Sul city and an outpatient unit in Turucu city employed the DES in Jan 2000, Jan 2001 and June 2003, respectively. DES includes a digital ECG machine, standard computers, a modem connection, telecommunication software and fixed or mobile phones. It allows data to be recorded, transmitted for immediate analysis and stored. A cardiologist performs the ECG analysis remotely, via either fixed or mobile phone, using the same telecommunication software. A total of 1950 digital tele ECGs have been made in the three locations. The time between data transmission and analysis with online DES is around 9 min in online transmissions. The low cost of this system makes it useful and appropriate for small cities of developing countries where cardiologists are not available for on-site consultation. DES has promoted a significant improvement in the acute management of patients with a consequent decrease in the morbidity and mortality rates from cardiovascular diseases. PMID- 17271014 TI - An image-based analysis for classifying multimodal brain images in the image guided medical diagnosis model. AB - Classifying images into meaningful categories according to its imaging modalities is beginning to play an increasingly important role in providing a foundation on which to build the next generation of the medical database management system. Since medical images often represent some form of diagnosis capabilities, the ability to follow-up and classify these images to support doctor's diagnosis, treatment, and prescription is becoming a pressing issue. This paper proposed to introduce a method for classifying input images in association to their diseases and diagnosis. We studied the connection between disease and its tumor image properties in three different image perspectives: binary image, intensity image and selected-pixel intensity image. Binary and intensity image slice profiling are based on texture and shape-based classification technique while selected pixel intensity image slice profiling is based on content-based classification technique. In this study, we looked at whether gender and age has played any role during input images slice profiling of both healthy and cancer patients. Experimental results reveal our algorithms suitability in classifying input images using the pixel-based approach for multimodal image datasets. PMID- 17271015 TI - An open strategy for implementing PACS and its primary application. AB - The strategy for implementing PACS in China is currently hospital-oriented, that causes difficulties of transferring patients among hospitals and sharing patients' images and other case information among doctors. To overcome such shortcomings, an open strategy, which is patient-oriented, was presented. In the open strategy, connections among all the hospitals could be established through Internet by image center, and patient-oriented mechanism also covers the courses of image archiving and other case information management, that would make the limited resources of experienced doctors sharable among all the patients effectively. Moreover, the security, authenticity and validity of patients' images and other case information could be guaranteed better than before. A primary application on probation of PACS implemented with such an open strategy, which was put into practice in China, was also presented. According to the results, the open strategy could extend the application area of PACS from large hospitals to small ones and expedite building of electrical hospitals in China. PMID- 17271016 TI - Engineering managed care automation via the treatment planning process: a bottom up approach. AB - This paper describes implementing technology used for developing a personalized treatment plan using a specific treatment planning process and methodology. This methodology involves defining categories of treatment, goals that a program can assist patients to achieve, client objectives that evidence movement towards achieving specific goals, and interventions that can be performed by the program to accomplish these objectives. Each goal is issued a start and end (review) date. At the review date, whether a patient accomplished the goal or not will be assessed by a clinician using acceptable testing methods. Staff intervene according to the objectives for which the intervention has been designated and chart against these objectives by comments and assigning a progress indicator. Using this methodology which includes these two disjoint measures, care facilities can utilize technology to employ a paperless system that will standardize the process for developing a person-centered plan, identify program and staff deficiencies, evaluate the effectiveness of changes made to the program with respect to staff and patients, and capture information necessary to produce detailed billing. Software that implements this method has successfully been employed at the Rose Hill Center for Psychiatric Treatment & Rehabilitation in less than six months. Facilities using this software can transfer patients between programs and keep a longitudinal patient record. Funding has been granted to use this software to study best practices in the treatment of schizophrenia and schizoaffective disorder. PMID- 17271017 TI - Remote expert system of support the prostate cancer diagnosis. AB - This paper presents the development of a remote expert system in urological area to support the prostate cancer diagnosis. The prostate cancer is one of the most common cancers among men and the second most frequent death cause by cancer in men. The combination of expert system with the benefits of remote computing allows that several doctors and client applications of urological area use the benefits of expert system of support the detection of prostate cancer. Once updated the expert system, it is automatically available for use. The rules of the expert system are applied to prostate cancer, and the diseases that puzzle the doctor in the cancer evaluation. The system was tested with real clinical cases for the evaluation of the results of the expert system in comparison with the result the last biopsy of these patients evaluated. The expert system presented good results, showing a great potential to support the physicians in the diagnosis of prostate cancer. PMID- 17271018 TI - DESSA: a new decision support system for neurosurgery. AB - DESSA is a new decision support system that addresses an open multidisciplinary group of medical care providers (users) working in the area of epilepsy. DESSA is the result of a close collaboration between engineers, medical doctors, and market analysts. Its architecture provides the user with an integrated electronic working domain handling diverse types of information and medical records. DESSA enables the user to make a decision based on the identification of critical interaction factors amongst predefined data categories through a correlations model on the integrated clinical picture of the patient in real time. The term integrated clinical picture refers to the ability of the system to record, describe, and classify in time the epileptic events on the basis of their type, frequency of occurrence, duration of symptoms, and correlate with respective pharmacological treatment and period of its application as well as respective specialized EEG and vEEG pictures. PMID- 17271019 TI - Towards ethical decision support and knowledge management in neonatal intensive care. AB - Recent studies in neonatal medicine, clinical nursing, and cognitive psychology have indicated the need to augment current decision-making practice in neonatal intensive care units with computerized, intelligent decision support systems. Rapid progress in artificial intelligence and knowledge management facilitates the design of collaborative ethical decision-support tools that allow clinicians to provide better support for parents facing inherently difficult choices, such as when to withdraw aggressive treatment. The appropriateness of using computers to support ethical decision-making is critically analyzed through research and literature review. In ethical dilemmas, multiple diverse participants need to communicate and function as a team to select the best treatment plan. In order to do this, physicians require reliable estimations of prognosis, while parents need a highly useable tool to help them assimilate complex medical issues and address their own value system. Our goal is to improve and structuralize the ethical decision-making that has become an inevitable part of modern neonatal care units. The paper contributes to clinical decision support by outlining the needs and basis for ethical decision support and justifying the proposed development efforts. PMID- 17271020 TI - Automatic 3D vascular tree construction of perforator flaps for plastic surgery planning. AB - Perforator flaps have been increasingly used in the past few years for trauma and reconstructive surgical cases. With the thinned flap design, greater survivability and a decrease in donor site morbidity have been reported. Knowledge of the 3D vascular tree will provide insight information about the dissection region, vascular territory, and fascia levels. In this paper, we will propose a computational framework for the automatic 3D vascular tree construction. The computational framework begins with an image segmentation algorithm, spedge-and-medge, which is an integration of Canny edge detector, edge linking, and split-and-merge to initially segment out the vessels from the background. To deal with the possible broken vessels, a vascular cross-sectional tree repairing and interpolation algorithm is then developed based on the 3D connectivity and root-converging properties of the tree branches. Furthermore, to extract the essential characteristics of the vascular structure, 3D thinning algorithms are used to build up the skeletons of the tree. At each stage of the framework, 3D rendering results are provided for the visualization of the computed results. The proposed method achieves good performance and has been used for the 3D vascular tree construction and surgical danger zone measurements on 39 harvested cadaver perforator flaps with the types of ALTP, GAP, and TAP. PMID- 17271021 TI - Damper design for improving S/N ratio of the seismocardiogram monitoring in the OpenMRI-guided operating theater. AB - The final goal of this study is to establish a method of measuring precisely the seismocardiogram (SCG) of a patient who lying in an open magnetic resonance imaging (openMRI) machine for myocardial ischemia monitoring during surgery. Vibration isolation from the gantry vibration during MRI scan is essential for clinical use. Authors previously reported the comparison between the SCG and the gantry vibration. A damper to decrease vibration below 30 Hz should be designed. In this paper, authors fabricated a damper model to check the feasibility of the damping effect, and compared with the patient bed mat. Experiment using a vibrator showed 1) the viscosity damping coefficient of the current damper was 2 kN s/m, 2) owing to the damper, peak ratio between input and output amplitude decreased from 2.5 to 1.2, and 3) natural frequency decreased from 12 Hz to 5 Hz. Damping below 30 Hz was successfully achieved. The maximum S/N ratio was calculated 6, improving from 1.8. Simulation showed that the maximum S/N would be 75 under the viscosity damping coefficient of 1 N s/m. PMID- 17271023 TI - Determining critical values of calculated parameters within a physiologic model. AB - To determine the critical value of calculated but not readily measurable variables of a physiologic model, we examine clinical studies of similar variables and establish the critical values. The calculated variables considered in this study are the partial pressure of oxygen in the myocardium and in the gray matter of the brain. Partial pressure target values of 29 mmHg for cerebral tissue and 23 mmHg for myocardial tissue were determined to be suitable for a critical threshold. We validated these with a physiologic model test by ensuring that these corresponded to a reasonable value of cardiac output, vital sign commonly used to evaluate patient well being. These values can be used for future analysis of physiologic monitors' alarm systems when using physiologic models. PMID- 17271022 TI - Using the full scale 3D solid anthropometric model in radiation oncology positioning and verification. AB - This paper describes the full size solid 3D Anthropometric Model using in the positioning and verification process for radiation treatment planning of the skull of cancer patients in radiotherapy. In order to obtain a full scale 3D, solid Anthropometric Model, data is first collected through computed tomography and optical scanning. Through surface reconstruction, a model is made of the patients skull, after which rapid prototyping and rapid tooling is applied to acquire a 1:1 solid model, thus, it can replace the patient for the tumor positioning and verification in radiotherapy. The 3D Anthropometric Model are not only provide a clear picture of the external appearance, but also allow insight into the internal structure of organic bodies, which is of great advantage in radiotherapy. During radiotherapy planning, 3D Anthropometric Model can be used to simulate all kinds of situations on the simulator and the linear accelerator, without the patient needing to be present, so that the medical physicist or dosimetrist will be able to design a precise treatment plan that is tailored to the patient. The 3D Anthropometric Model production system can effectively help us solve problems related to r adiotherapy positioning and verification, helping both radiotherapists and cancer patients. We expect that the application of 3D Anthropometric Model can reduce the time that needs to be spent on pretreatment procedures and enhance the quality of health care for cancer patients. PMID- 17271024 TI - Development of an implantable intrathecal drug infusion pump. AB - An intrathecal drug infusion system has been designed, manufactured and tested. The system is composed of a drug reservoir and a pump/controller assembly. The drug reservoir made of SUS316L is a negative pressure gas chamber enclosing a bellows type drug chamber. The pump/controller assembly includes a bacterial filter, a controller circuit board, a battery and a micropump, and is connected to a catheter for intrathecal infusion. The micropump implements a peristaltic pumping of the drug by a sequential motion of three pairs of cam and cam follower. In vitro performance tests were conducted with prototypes. PMID- 17271025 TI - The shape of electrical impedance spectroscopy (EIS) is altered in stroke patients. AB - The shape of the Power Spectral Density Function (PSD) of the Electrical Field Distribution exhibit abnormalities in the brain structure when comparing chronic stroke patients with healthy volunteers. We built a System that can deliver White Noise currents in the 0-25kHz band to any electrode pair. The System is also capable of measuring potentials with a high-dynamic range (24 Bits) from eight pairs of shielded electrodes placed on the subject's head and lying on an axial plane approximately 3 cm above inion. In the stroke patients, the asymmetry in the CSF distribution in the brain modifies the spatial components of the scalp potentials with respect to healthy volunteers. PMID- 17271026 TI - A wireless ECG smart sensor for broad application in life threatening event detection. AB - A single channel wireless, wearable ECG smart sensor has been developed for long term monitoring of patients at risk of life-threatening cardiac arrhythmias. The battery-operated sensor can be applied in virtually any orientation on the upper left quadrant of the chest, and monitors patient health continuously for up to three days. An embedded microcontroller calculates heart rate and monitors the ECG signal for life-threatening arrhythmias, which are transmitted wirelessly to a central server and relayed to a respondent device. Tests on human subjects demonstrated signal amplitude from the closely-spaced smart sensor electrodes to be one-half that of the best vector from traditional limb lead placement. Tests with motion and muscle artifact showed superior noise immunity by the smart sensor as compared to a state-of-the-art telemetry monitor. PMID- 17271027 TI - Mobile medical device connectivity: real world solutions. AB - Mobile medical devices, such as infusion pumps, provide an important therapeutic function. They are also valuable sources of information about treatment patterns at the point of care. However, these mobile devices have been independent islands of valuable information, unable to share the data they gather with other hospital information resources on a real time basis. Although data from these devices can provide significant improvements for medical safety and vital information needed for clinical best practice development, gathering that data poses significant challenges when interfacing with hospital information systems. Mobile medical devices move from place to place as independent actors, raising a series of security and identification issues when they need to be disconnected and reconnected using traditional tethered cable connections. The continuing lack of accepted communications protocol standards, in spite of the concentrated efforts of organizations like the IEEE and the Medical Information Bus (IEEE 1073) to establish them, has made integration into the hospital information system a complex and non-standard task. The rapid spread in availability and adoption of high-speed 802.11 wireless systems in hospitals offers a realistic connectivity solution for mobile medical devices. Inspite of this, the 802.11 standard is still evolving, and current security methods designed for user-based products like PDAs and laptop computers are not ideal for unmanned mobile medical devices because they assume the availability of a human operator to authenticate a wireless session. In the absence of accepted standards, manufacturers have created practical and innovative solutions to support the collection of clinical data from mobile medical devices and the integration of that data with hospital information systems. This paper will explore the potential benefits of integrating mobile medical devices into the hospital information system, and describe the challenges in developing connectivity for such system based on actual experience with the implementation of wired, wireless, and hybrid systems in active medical environments. PMID- 17271028 TI - End tidal carbon dioxide measurement using an electro acoustic sensor. AB - End tidal carbon dioxide measurement with an electro-acoustic sensor is demonstrated. The sensor consists of an acoustic resonator coupled to a low cost electro-acoustic element. By simultaneous measurements with a reference sensor, the new device was tested on subjects performing exercise, hypo- and hyperventilation whereby the CO2concentration ranged from 2.1 to 7.0 kPa. The output from the experimental device correlated well with the reference CO2readings with a correlation coefficient of 0.976. Response time for expiration less than 0.8 seconds was noted. The new device could be useful in situations where selectivity to other gases is not important. PMID- 17271029 TI - Estimation of beat-to-beat systolic blood pressure using pulse arrive time and pulse width derived from the photoplethysmogram. AB - Continuous arterial blood pressure monitoring is essential in monitoring patients during surgical operation or in intensive care units. In this study, we propose a new method to estimate beat-to-beat systolic blood pressure by combining the pulse arrive time and normalized pulse width measurement. The method was examined in nine patients who were in ICU. Results shows the new method has higher linearity (0.8218) and better precision (3.0775) than the methods using either pulse arrive time or pulse width only. PMID- 17271030 TI - Automated agitation management accounting for saturation dynamics. AB - Agitation-sedation cycling in critically ill is damaging to patient health and increases length of and cost. A physiologically representative model of the agitation-sedation system is used as a platform to evaluate feedback controllers offering improved agitation management. A heavy-derivative controller with upper and infusion rate bounds maintains minimum plasma concentrations through a low constant infusion, and minimizes outbursts of agitation through strong, timely boluses. controller provides improved agitation management using from 37 critically ill patients, given the saturation of effect at high concentration. Approval was obtained the Canterbury Ethics Board for this research. PMID- 17271031 TI - Adaptive bolus-based set-point regulation of hyperglycemia in critical care. AB - Critically ill patients are often hyperglycemic and extremely diverse in their dynamics. Consequently, fixed protocols and sliding scales can result in error and poor control. A two-compartment glucose-insulin system model that accounts for time-varying insulin sensitivity and endogenous glucose removal, along with two different saturation kinetics is developed and verified in proof-of-concept clinical trials for adaptive control of hyperglycemia. The adaptive control algorithm monitors the physiological status of a critically ill patient, allowing real-time tight glycemic regulation. The bolus-based insulin administration approach is shown to result in safe, targeted stepwise glycemic reduction for three critically ill patients. PMID- 17271032 TI - Construction of a conformal water bolus vest applicator for hyperthermia treatment of superficial skin cancer. AB - Large area chestwall recurrence of breast carcinoma can be treated with moderate temperature hyperthermia in combination with radiation or chemotherapy. For diffuse chestwall disease, hyperthermia is best delivered with a conformal microwave array (CMA) applicator using a temperature-controlled water bolus designed specifically to fit complex contours and maintain contact with the tissue surface to prevent air gaps which distort the microwave power deposition pattern. In order to maintain the desired temperature range of 41-45 degrees C during local hyperthermia treatments, it is necessary to have an effective fluid flow system to serve as a buffer and prevent overheating of skin, which can lead to small blisters or, in rare cases, deeper burns. The fluid flow dynamics of a vest shaped open water bag design is evaluated with thermometry during a step temperature change of circulating water. The data confirm the feasibility of uniform circulation and temperature control throughout complex bolus shapes. This water bolus design should improve temperature uniformity of current treatments for superficial tissue disease. PMID- 17271033 TI - A technology roadmap for rehabilitation engineering. AB - During September 2003, interviews took place to collect data to develop a technology roadmap for rehabilitation engineering. The emerging themes were used to create the roadmap. Criteria were developed to endorse the data prior to the representation process. Added value was by the collection and representation of supporting evidence. Roadmapping 'best practice will facilitate the capture of essential data, represented in a format that is accessible, delivered in an appropriate format, to the right person at the right time. PMID- 17271034 TI - Automatic characterization of events on SpO2 signal: comparison of two methods. AB - Two methods based on trend extraction have been designed to provide automatic analysis of physiological data recorded on adult patients hospitalized in intensive care unit. We focused our work on the characterization of events occurring on SpO2 signal, this signal being used to detect vital problems. Our aim was to recognize events related to technical or vital problems to assist medical staff in his decision process. Our results show that both methods are able to detect and distinguish between probe deconnection, transient hypoxia and desaturation events. PMID- 17271035 TI - Neural networks for predicting technological use in neonatal care. AB - Health care providers are increasingly concerned about the rising costs of the Neonate Intensive Care Units (NICU) and therefore a model that accurately predicts the technological use can be potentially beneficial for health care planning. This paper concerns the assessment of neural networks for predicting the use of GASOMETRY in a Brazilian NICU. Our results show that neural networks may not be superior to multiple linear regression models when no clear non-linear relationship exists. PMID- 17271036 TI - Application of spectral entropy to EEG and facial EMG frequency bands for the assessment of level of sedation in ICU. AB - The applicability and performance of spectral entropy as a measure of the depth of sedation was studied by comparison to the Richmond sedation and agitation scale (RASS). A biopotential signal was measured from the forehead of eight ICU patients. From this biopotential four different frequency bands were defined using trend fitting to the low and high frequency limits of the pooled power spectra, two frequency bands representing EEG and the other two representing fEMG. The spectral entropy from the EEG bands correlated very well with the sedation levels of RASS. From levels 0 to -5 the decrease was almost linear (r=0.51 and r=0.53). A similar comparison for the spectral entropy of the fEMG bands did not produce any clear correlation (r=0.07 for both fEMG bands), however there was still some clear interaction at some levels. It seems that the RASS is dependent upon both EEG and fEMG effects. That is; RASS is related to both cortical and sub-cortical components of sedation. PMID- 17271037 TI - Evaluating alternative service contracts for medical equipment. AB - Managing medical equipments is a formidable task that has to be pursued maximizing the benefits within a highly regulated and cost-constrained environment. Clinical engineers are uniquely equipped to determine which policies are the most efficacious and cost effective for a health care institution to ensure that medical devices meet appropriate standards of safety, quality and performance. Part of this support is a strategy for preventive and corrective maintenance. This paper describes an alternative scheme of OEM (Original Equipment Manufacturer) service contract for medical equipment that combines manufacturers' technical support and in-house maintenance. An efficient and efficacious organization can reduce the high cost of medical equipment maintenance while raising reliability and quality. Methodology and results are discussed. PMID- 17271038 TI - Targeting shock waves in human tissue for extracorporeal shock wave therapy. AB - Extracorporeal Shock Wave Therapy is a relatively new alternative method to surgery for the treatment of many bone and muscle disorders. Currently, targeting of shock waves in the human body is done using either ultrasound or x-ray imaging. Many studies have shown controversial treatment results with conclusions that criticize ultrasound targeting. Here it is shown that targeting of the shock waves inside the body is crucial to the result of a treatment. The two different coupling methods of the shock wave generator onto the patient's body are used with gelatin phantoms to give insight into the actual treatments. As a conclusion, x-ray imaging or inline ultrasound with direct coupling should be preferred. In addition, the path of the shock waves should be vertical to the bone surfaces in order to preserve a focal region in the treated area. PMID- 17271039 TI - Applications of the Petri net to simulate, test, and validate the performance and safety of complex, heterogeneous, multi-modality patient monitoring alarm systems. AB - This research is motivated by the rapid pace of medical device and information system integration. Although the ability to interconnect many medical devices and information systems may help improve patient care, there is no way to detect if incompatibilities between one or more devices might cause critical events such as patient alarms to go unnoticed or cause one or more of the devices to become stuck in a disabled state. Petri net tools allow automated testing of all possible states and transitions between devices and/or systems to detect potential failure modes in advance. This paper describes an early research project to use Petri nets to simulate and validate a multi-modality central patient monitoring system. A free Petri net tool, HPSim, is used to simulate two wireless patient monitoring networks: one with 44 heart monitors and a central monitoring system and a second version that includes an additional 44 wireless pulse oximeters. In the latter Petri net simulation, a potentially dangerous heart arrhythmia and pulse oximetry alarms were detected. PMID- 17271040 TI - Failure mode effect analysis applied to the use of infusion pumps. AB - Failure Mode Effect Analysis (FMEA) offers a prospective approach to reducing the risk associated with health care delivery. Beginning in February, 2002, an interdisciplinary team of fifteen individuals, including end-users, conducted an FMEA for the use of infusion pumps at UCSF Medical Center. The use of infusion pumps was identified as the area of highest risk, based on incident report data. The team identified sixteen potential failure modes, including their potential effects and causes, and assigned a risk priority number to each based on the potential severity, probability, and detectability of the failure. Notable failure modes included: incorrect programming; improper or inconsistent labeling of solution, tubing, and pump; potential use of malfunctioning or damaged pumps; and incorrect programming by nurses related to device design. The team then broke into smaller work groups and invited more end-users to perform root cause analyses and suggest recommended actions/outcome measures for each failure mode with a risk priority number of 32 or higher (on our scale of 1 to 64). Finally, the FMEA team assembled all of the data, prepared a final report, and assigned responsibility for key recommended actions. PMID- 17271041 TI - Improving health care systems following an incident investigation. AB - All health care is delivered to patients through an assemblage of minisystems. (A minisystem is the smallest system that can deliver a single clinical benefit.) It is the failure of these minisystems that reportedly results in between 44,000 and 98,000 iatrogenic deaths in the United States, annually. Device-related, accident investigations are intended to identify the latent defects within these minisystems and to recommend corrective actions that will prevent a recurrence. A generic, system's risk model has been developed for analyzing the performance of these minisystems. It provides the investigator with a mental model of the interacting components of the minisystem and provides a logical pathway toward the root causes of an adverse event. Of practical importance in using this model, is that operator error contributes to approximately 69% of the failures of health care minisystems and a fundamental understanding of human factors and human error is required. PMID- 17271042 TI - The square peg and the round hole: Murphy's Law and medical device connections. AB - Engineers have long been aware of Murphy's Law: If anything can go wrong, it will. When applied to medical device design, Murphy's Law indicates that if there is a way that a medical device can be set up incorrectly then someday, somewhere it will be set up incorrectly. In the clinical environment the result may be patient injury or death. Despite this received wisdom, clinical engineers continue to encounter examples of medical device design that invite users to do the wrong thing, with potentially harmful results. This paper focuses on electrical and other connectors incorporated into medical device designs. Examples of potential and actual misconnections, from the earliest days of clinical engineering to the present, are presented and discussed. PMID- 17271043 TI - Risk assessment - hospital view in selecting medical technology. AB - Appropriate deployment of technological innovation contributes to improvement in the quality of healthcare delivered, the containment of cost, and access to the healthcare system. Hospitals have been allocating a significant portion of their resources to procuring and managing capital assets; they are continuously faced with demands for new medical equipment and are asked to manage existing inventory for which they are not well prepared. To objectively direct their investment, hospitals are developing medical technology management programs that need pertinent information and planning methodology for integrating new equipment into existing operations as well as for mitigating patient safety issues and costs of ownership. Clinical engineers identify technological solutions based on the matching of new medical equipment with hospital's objectives. They review their institution's overall technological position, determine strengths and weaknesses, develop equipment-selection criteria, supervise installations, train users and monitor post procurement performance to assure meeting of goals. This program, together with consistent assessment methodology and evaluation analysis, will objectively guide the capital assets decision-making process. At Texas Children's Hospital we integrated engineering simulation, bench testing and clinical studies with financial information to assure the validity of risk avoidance practice and the promotion of medical equipment and supplies selection based on quantitative measurement process and product comparison practice. The clinical engineer's skills and expertise are needed to facilitate the adoption of an objective methodology for implementing the program, thus improving the match between the hospital's needs and budget projections, equipment performance and cost of ownership. The result of systematic planning and execution is a program that assures the safety and appropriateness of inventory level at the lowest life cycle costs at the best performance. PMID- 17271044 TI - A thirty-two year perspective on a clinical engineer's contributions to patient safety. AB - Clinical Engineers (CE's) and Clinical Engineering departments began appearing in hospitals a little over thirty years ago. The impetus for their creation was often based on a single patient safety issue. From those early days to now, the contributions of CE's to patient safety problems and issues has spanned many topics and operations. The experiences of one CE are presented and illustrated by several examples of patient safety issues and the CE department involvement in patient safety improvement through individual, department, and committee efforts. PMID- 17271045 TI - Cost management of medical equipment maintenance. AB - In the present study we combine Activity Based Costing (ABC) with a microprocess based custom-made management system used to control of the medical equipment maintenance service performed by a clinical engineering group in a public health institution in Brazil. Results show the cost of service orders calculated through the allocation of the expenditure per cost center to activities performed during the year 2003. As this model can estimate how the activities affect profitability, managers can use ABC information to interpret possible strategies needed to investigate the viability of cost minimization. PMID- 17271046 TI - Medical device security. AB - Medical device security represents a growing problem within the healthcare industry. An increasing number of medical devices and systems contain critical health related information for which integrity, availability, and confidentiality must be maintained. HIPAA's Security Rule requires that US healthcare providers have a security program addressing this problem in place by April 21, 2005. Through a collaborative effort, ACCE and ECRI have developed the first comprehensive guideline for implementing the security management and risk analysis process for medical technology. PMID- 17271047 TI - Electromagnetic interference to infusion pumps from GSM mobile phones. AB - Electromagnetic interference (EMI) to critical care medical devices has been reported by various groups. Previuos studies have demonstrated that infusion and syringe pumps are susceptible of false alarm buzzing and block, when exposed to various EMI sources. Whether these events may have clinical relevance is still debated. The risk of EMI depends on several factors such as phone emitted power, distance and carrier frequency. We investigated the EMI on infusion and siringe pumps from GSM phones at various distances and emitted powers. Malfunctions were observed in 4/7 infusion pumps and 1/4 syringe pumps exposed to mobiles at their maximum output, for distances as long as 30 cm. The maximum power not inducing any malfunction even at 0 cm distance was also determined. The selection of a proper maximum power class reduces significantly the risk of EMI. Such a function is already built in the GSM standard and thus represents one of the feasible solutions to the EMI problem in hospitals. PMID- 17271048 TI - Benchmarking clinical engineering program. AB - Professional labor shortage in healthcare delivery system and specifically the management of staffing effectiveness in clinical engineering field are recent developments where shortage of comparative information exist and almost no information on its impact on performance outcomes. We attempted over the past few years to define and measure optimal application of manpower to medical technology management in the hospital setting. PMID- 17271049 TI - Directed evolution of AAV mutants for enhanced gene delivery. AB - Gene therapy vehicles must be engineered to overcome numerous barriers that limit delivery efficiency. These barriers arise at every step of the delivery process, including the transit of the vector from injection to a cell surface, receptor binding and uptake, intracellular trafficking, and nuclear entry. The gene transfer properties of the highly promising adeno-associated viral (AAV) vector at each step are determined by its capsid structure. Previous capsid modifications that alter AAV tropism, as well as the existence of multiple AAV serotypes, suggest that the AAV capsid is reasonably plastic. We have taken advantage of this remarkable capsid plasticity to generate a large mutant AAV library (1e6) and select for mutant AAV virons that can overcome several barriers to infection. Specifically, we have selected AAV2 library for infectious particles with altered heparan sulfate (HS) affinity and for the ability to evade an AAV2 immune response. We have generated mutants with lower and higher affinity to heparin, which could prove valuable in controlling the therapeutic zone of an AAV vector in tissues where ECM HS hinders AAV2 diffusion. Furthermore, we have generated vector variants that have resistance to human serum that neutralizes wild type AAV2, yet retain AAV2 gene delivery efficiency. These vectors may enable high gene delivery efficiency even in patients with preexisting immunity, and the locations of point mutations on the capsid surface suggest new regions of functional importance to the virus. These AAV libraries therefore both provide useful variants for gene therapy application and offer a means to dissect AAV biology. PMID- 17271050 TI - Systemic virus dissemination during local gene delivery in solid tumors and its control with an alginate solution. AB - Intratumoral infusion, a routine method for local gene delivery in solid tumors, may cause a systemic dissemination of gene vectors. This is because tumor vessels are intrinsically leaky and intratumoral injection can also result in damage of tumor vessels. To this end, we investigated the extent of virus dissemination during and after local infusion of adenoviral vectors into a murine adenocarcinoma (4T1) transplanted in mice. Three different vectors were used in this study, they contained genes encoding either mouse interleukin-12 (IL-12), luciferase, or enhanced green fluorescence protein (EGFP). The virus distribution in the body was determined as the transgene expression in normal and tumor tissues. Our data demonstrated that a large fraction of injected viral vectors disseminated into liver tissues. To reduce the dissemination problem, we developed a novel method for viral vector delivery based on an alginate solution. We observed that this vehicle could significantly reduce virus dissemination without compromising the therapeutic efficacy of adenoviral vectors. Taken together, the data suggests that systemic virus dissemination is a serious problem in local gene therapy in tumors and that the dissemination can be significantly reduced by an alginate-based polymeric vehicle. PMID- 17271051 TI - Ultrasound enhancement of drug release across non ionic surfactant vesicle membranes. AB - Nonionic surfactant vesicles (niosomes) have potential applications in targeted drug delivery and imaging because of their ability to encapsulate therapeutic agents and their enhanced uptake by physiological membranes. Ultrasound may be used to mediate delivery non-invasively by altering the niosome membrane structure. Niosomes composed of polyoxyethylene sorbitan monostearate (Tween 61), cholesterol, and dicetyl phosphate were synthesized via a thin film hydration technique. A fluorescing dye, carboxyfluorescein (CF), was encapsulated and used as a drug model. The amount of dye in the niosomes, the concentration of the vesicles, and their mean particle size after each 5 minute incremental exposure to ultrasound were monitored. Dye concentration encapsulated by the niosomes in the samples decreased while the population and size distribution of the niosome remained largely unchanged. Our conclusion is that ultrasound enhances the rate of dye diffusion across the niosome membrane non-destructively. PMID- 17271052 TI - Sonoporation of cells for drug and gene delivery. AB - Recent studies demonstrate that ultrasound can be used to deliver compounds into viable cells for potential targeted drug delivery and non-viral gene transfection, revealing new, advantageous possibilities. The delivery is facilitated through sonoporation, the formation of temporary pores in the cell membrane induced by ultrasound. Our study focuses on the study of sonoporation mechanisms in order to achieve optimal delivery outcome such as high delivery efficiency and minimal cell death. Using voltage clamp techniques, we obtained real-time measurements of sonoporation of single Xenopus oocytes in the presence of Optison, an agent consisting of albumin-shelled C3F8 gas bubbles. Ultrasound increased the transmembrane current as a direct result of decreased membrane resistance due to pore formation. The ability to real time monitor sonoporation of cells provides a novel and necessary tool for us to study the dynamic sonoporation process and obtain optimal delivery parameters. We confirmed the delivery of compound into cells by using markers such as plasmid GFP. PMID- 17271053 TI - Applying models of targeted drug delivery to gene delivery. AB - Gene delivery requires targeted delivery systems. Exploratory simulations using models of targeted drug delivery helps one assess the worthiness of such systems, and helps quantify the expected therapeutic benefits of the systems. The drug targeting index (DTI), a ratio of availabilities, is a measure of pharmacokinetic benefit of the delivery device, based on a combination of a physiologically-based pharmacokinetic model and a single pharmacodynamic Emaxmodel. Pharmacodynamic outcomes are quantified by the degree of separation between the dose-response and dose-toxicity curves (SRT). Simulations are undertaken to investigate the potential linkage of DTI and SRT, a pharmacodynamic outcome. A significant positive linear relationship is found between the DTI and SRT. The relationship can be translated into a minimum pharmacokinetic requirement that can be used to guide making decisions regarding whether or not further pursue the development of a candidate gene-delivery device as a therapeutic agent. PMID- 17271054 TI - Quantitative description and model of molecule transport through skin. AB - The illustration of the electrical properties of skin and quantitative relations provides the theory and method for transdermal drug delivery by electroporation. The paper puts forward an electrical model of skin including conductance of appendageal, lipid, lipid-corneocyte matrix pathway and Nernst potential of charged drug molecule. Leakage experiments with Tinidazole as pattern mass were carried out with three groups, each of which contained 15 protocols. The result indicates that (1) we obtained that equivalent resistance R(T) of side-by-side permeation chambers and one R(A) of transdermal decreased along with initial voltage of pulse increased using logarithm trend line fitting, but the R(T) and R(A) were gained along with pulse voltage decreased during pulse duty; (2) Even if same pulse protocol, Tinidazole permeation fluxes were difference 0-4 orders from each other for SC of different position at same time. The transdermal potential is actual exist in the molecular to pass through skin. In is more significant that conductance Ga, Gl and Gc is described permeability of molecular through skin. And it shows that electrical model of skin to expatiate quantify relationship between electrical property and molecular flow is very effective. PMID- 17271055 TI - Investigations of needle-free jet injections. AB - Jet injection is a needle-free drug delivery method in which a high-speed stream of fluid impacts the skin and delivers drugs. Although a number of jet injectors are commercially available, especially for insulin delivery, they have a low market share compared to needles possibly due to occasional pain associated with jet injection. Jets employed by the traditional jet injectors penetrate deep into the dermal and sub-dermal regions where the nerve endings are abundantly located. To eliminate the pain associated with jet injections, we propose to utilize microjets that penetrate only into the superficial region of the skin. However, the choice of appropriate jet parameters for this purpose is challenging owing to the multiplicity of factors that determine the penetration depth. Here, we describe the dependence of jet injections into human skin on the power of the jet. Dermal delivery of liquid jets was quantified using two measurements, penetration of a radiolabeled solute, mannitol, into skin and the shape of jet dispersion in the skin which was visualized using sulforhodamine B. The dependence of the amount of liquid delivered in the skin and the geometric measurements of jet dispersion on nozzle diameter and jet velocity was captured by a single parameter, jet power. PMID- 17271056 TI - The development of novel flexible electrode arrays for the electrochemotherapy of solid tumour tissue. (Potential for endoscopic treatment of inaccessible cancers). AB - Therapeutic "electroporation" involves application of electric fields to target cells/tissues, thereby rendering their cell membranes transiently porous, thus making feasible the cellular uptake and efficacy of previously impermeant and ineffective therapeutic agents. The objectives of this research are a) the development of flexible electrode arrays for incorporation into microsystem endoscopic devices, and b) the assessment of their efficacy in delivering selected genetic and pharmaceutical anticancer therapies. Gold electrodes were fabricated on flexible polyimide substrates following predictive modeling and simulation of electric fields using FEMLAB software. Subsequent assessment of electroporation efficiency in-vitro involved 1) enumeration of viable tumour cells after delivery of electric pulses and exposure to low concentrations of bleomycin, otherwise known as electrochemotherapy 2) Efficacy of gene delivery by detection of emitted green fluorescence by cells after electroporation with the pEGFP plasmid and 3) In-vivo efficacy of electrochemotherapy in a variety of human solid tumour masses in nude mouse models (xenografts). The flexible electrode system was found to be successful for electrical delivery of plasmids and drugs in-vitro and in-vivo. We found in-vivo complete regression of prostate, colon, oesophageal, and renal cancers with reduced growth rates for fibrosarcoma and breast cell lines. These flexible electrodes are suitable for electrochemotherapy or gene therapy to solid tumours masses and may be fabricated for application to the treatment of some cancers in humans by transcutaneous or endoscopic delivery systems. PMID- 17271057 TI - Sequential finite element model of tissue electropermeabilisation. AB - Sequential model of liver tissue electropermeabilisation around two needle electrodes was designed by computing electric field (E) distribution by means of the finite element (FE) method. Sequential model consists of a sequence of static FE models which represent E distribution during tissue permeabilisation. In the model an S-shaped dependency between specific conductivity and E was assumed. Parameter estimation of S-shaped dependency was performed on a set of current measurements obtained by in vivo experiments. Another set of in vivo measurements was used for model validation. Model validation was carried out in three different ways by comparing experimental measurements and modelled results. The model validation showed good agreement between modelled and measured results. The model also provided means for better understanding processes that occur during permeabilisation. Based on the model, the permeabilised volume of tissue exposed to electrical treatment can be predicted. Therefore, the most important contribution of the model is its potential to be used as a tool for determining the electrode position and pulse amplitude needed for effective tissue permeabilisation. PMID- 17271058 TI - Using models of the passive cardiac conductivity and full heart anisotropic bidomain to study the epicardial potentials in ischemia. AB - In this paper we present a multi-scale approach for cardiac modeling. Based on the histology of cardiac tissue we created a geometrical model at a cellular scale to compute the effective conductivity of a piece of cardiac tissue. In turn, the conductivity values obtained from this cellular scale model were used in a whole heart model in which we simulated regional, subendocardial ischemia. Histological changes at a cellular level led to changes in the effective conductivity tensor of the tissue, which in turn resulted in changes in the epicardial potential patterns during the ST-interval. Two effects were studied using this multi-scale approach: (1) the influence of a dynamically growing ischemic region on the epicardial potentials, and (2) the influence of a dynamically changing conductivity in the ischemic zone due to changes in the underlying pathology. One specific finding was the presence of epicardial patterns consisting of a central elevation and two opposite depressions at the edges of the ischemic zone which rotated as the ischemia became more transmural. In addition, the epicardial potentials decreased in magnitude with the duration of the ischemia due to changes in the effective conductivity of the ischemic tissue predicted by the cellular level model. PMID- 17271059 TI - ECGSIM: an interactive tool for the study of the relation between the electric activity of the heart and the QRST waveforms at the body surface. AB - ECGSIM is an interactive computer program that solves the forward problem of electrocardiology. The user may set the depolarization and repolarization times at the heart surface, as well as the transmembrane potential amplitude. The program computes the resulting ECGs at the body surface. In this way, the effect of changes of the electric activity of the heart on the ECG can be studied. ECGSIM may be downloaded, free of charge, from the web. PMID- 17271060 TI - Forward modeling of ventricular electromechanical interactions: normal and failing hearts. AB - The goal of this study was to develop and validate a forward three-dimensional computational model of the dilated failing heart with left bundle branch block (LBBB) to investigate how BiV pacing can improve systolic mechanical performance and synchrony. Specialized finite element methods are used for simulating three dimensional electrical propagation and mechanics. PMID- 17271061 TI - Inverse electrocardiography in the framework of dynamic imaging problems. AB - We describe several current approaches which include temporal information into the inverse problem of electrocardiography. Some of these approaches operate directly on potential-based source models, and we show how three recent methods, introduced with rather distinct assumptions, can be placed in a common framework and compared. Others operate on parameterized models of the cardiac sources, and we discuss briefly how recent developments in curve evolution methods for inverse problems may allow more physiologically complex parametric models to be employed. PMID- 17271062 TI - The influence of volume conduction effects on the EEG/MEG reconstruction of the sources of the Early Left Anterior Negativity. AB - To achieve a deeper understanding of language processing in the human brain, scientists and clinicians use Electroencephalography (EEG) and Magnetoencephalography (MEG) inverse methods to reconstruct sources of Event Related Potentials. There exists a persistent uncertainty regarding the influence of volume conduction effects such as the anisotropy of tissue conductivity of the skull and the white matter layers on the inverse results. In this paper, we will study the sensitivity to anisotropy of the source reconstruction of the Early Left Anterior Negativity (ELAN) component in language processing. For EEG, the presence of tissue anisotropy substantially compromises the restoration ability of an L1-norm current density approach. The centers of activity are strongly shifted along the Sylvian fissure in the anterior direction. In contrast, MEG in combination with the L1 norm approach is able to reconstruct the main features of the ELAN source distribution even in the presence of anisotropic conductivity. PMID- 17271063 TI - Optical mapping system for recording action potential durations in adult mouse left and right atrium. AB - The increasing availability of murine models of the cardiovascular system has created a need for instrumentation and methods for assessing murine cardiovascular function. We have adapted an existing optical mapping system based on voltage-sensitive dyes to record from an isolated mouse atrial preparation. Initial results indicate that our approach is capable of recording action potentials from isolated mouse atria with sufficient signal quality to determine action potential duration (APD). Preliminary observations suggest that gradients in APD exist in the mouse atria and are similar to those observed in the atria of larger mammals. Future work with this technique will provide important information about mouse atrial electrophysiology and how it relates to that of larger mammals. PMID- 17271064 TI - High resolution optical mapping of cardiac action potentials in freely beating rabbit hearts. AB - Optical mapping of action potentials (APs) has become important tools for the cardiac electrophysiology. However, cardiac contraction unavoidably produces motion artifacts (MA) in optical signal. We developed a method to suppress motion artifacts without arresting the hearts. METHODS: Using a dual-wavelength optical mapping system, APs were recorded on the surface of an isolated rabbit heart. Transmembrane APs were simultaneously recorded using glass microelectrodes. We eliminated MA in a frontal plane by a motion tracking technique. Subsequently, a dual-wavelength ratiometric method was used to remove MA in a vertical direction to a frontal plane. RESULTS: MA were effectively removed from optical signals. Action potential duration measured from optical signals corresponded with those measured from microelectrodes (r2=0.9677). Our method enables us to map action potentials in freely beating hearts. PMID- 17271065 TI - Simulations of optical mapping during electroporation. AB - Experiments using optical mapping suggest that electroporation occurs in cardiac tissue when the transmembrane potential, Vm, is observed to be significantly less than +/- 400 mV. Our hypothesis, which we test by numerical simulation, is that Vm is greater than +/- 400 mV at the tissue surface, but optical mapping underestimates Vm because it averages over depth. Results indicate a significant underestimation of Vm. Experimental studies indicate a depolarization of the resting transmembrane potential, Vrest, after a strong shock. In a homogeneous model, electroporation only occurs near the tissue surface. Just as Vm during the stimulus is underestimated due to averaging, we hypothesize that the depolarization of Vrest is also underestimated. PMID- 17271066 TI - A study of the dynamics of cardiac ischemia using experimental and modeling approaches. AB - The dynamics of cardiac ischemia was investigated using experimental studies and computer simulations. An experimental model consisting of an isolated and perfused canine heart with full control over blood flow rate to a targeted coronary artery was used in the experimental study and a realistically shaped computer model of a canine heart, incorporating anisotropic conductivity and realistic fiber orientation, was used in the simulation study. The phenomena investigated were: (1) the influence of fiber rotation on the epicardial potentials during ischemia and (2) the effect of conductivity changes during a period of sustained ischemia. Comparison of preliminary experimental and computer simulation results suggest that as the ischemic region grows from the endocardium towards the epicardium, the epicardial potential patterns follow the rotating fiber orientation in the myocardium. Secondly, in the experimental studies it was observed that prolonged ischemia caused a subsequent reduction in the magnitude of epicardial potentials. Similar results were obtained from the computer model when the conductivity of the tissue in the ischemic region was reduced. PMID- 17271067 TI - Constructing a tissue-specific model of ventricular microstructure. AB - Simulations of cardiac electrical activity are generally computed in idealized or generic domains. We have developed a semi-automated technique for imaging an extended volume of cardiac ventricular tissue at a resolution of approximately 1 microm, and constructing from those images a geometric and structural model with 10 microm resolution suitable for solving the bidomain equations. This technique enables experimental modeling and computer simulation to be integrated by constructing a tissue-specific structural model in less than one week. We demonstrate the use of this procedure applied to a sample of rat ventricle. PMID- 17271068 TI - Conduction velocity in myocardium modulated by strain: measurement instrumentation and initial results. AB - Quantification of the relationship between strain and excitation velocity in cardiac muscle gives important insights into the significance and contribution of microstructure and several transmembrane proteins to cardiac electrophysiology. In this study we introduce a measurement and analysis system for quantification of the relationship in papillary muscle of small mammals, superfused and kept in a physiological environment. A novelty of the approach is the extensive automation and computerization of the measurement and analysis procedure. Initial results indicate that the conduction velocity is strain dependent in such a manner that several components contribute to establish this relationship. Further studies will help to quantify the relationship and importance of the components. PMID- 17271069 TI - ECG QRS complex detection using slope vector waveform (SVW) algorithm. AB - This paper presents an algorithm using Slope Vector Waveform (SVW) for ECG QRS complex detection and RR interval evaluation. The algorithm consists two parts of operations. They are variable stage differentiation and non-linear amplification. Variable stage differentiation is used to obtain the desired slope vectors for feature extraction, and the non-linear amplification is used to improve signal-to noise ratio Results show that, SVW provides excellent QRS detection even if the signals are contaminated with noises. The SVW algorithm is less computationally involved. This makes it ideal for a widely range of machine diagnosis applications, particularly, embedded real-time ECG monitoring. PMID- 17271070 TI - Comparing regularized B-spline neural network, multilayer perceptron and boosted CART on two problems of heart arrhythmia diagnosis. AB - Medical diagnosis has special requirements on reliability and interpretability of a learning scheme. Two problems in heart arrhythmia diagnosis are discussed in the paper 1) distinguish premature ventricular contraction beats from normal beats (Problem A); 2) distinguish premature ventricular contraction beats from premature atrial beats (Problem B). Analysis of the real clinical data shows that these two problems have different noise levels, which is suitable for addressing various requirements of medical domain. The performances and characteristics of three methods are compared: Regularized B-spline Neural Networks, Multilayer Perceptron and Boosted-CART using AdaBoost. Regularized B-spline Neural Network outperforms Multilayer Perceptron on the difficult Problem B, which suggests its potential in modeling complex system. Overall, Boosted-CART achieves best recognition rate with intermediate interpretability. PMID- 17271071 TI - Analysis of beat-to-beat variability of ventricular late potentials by a spectro temporal technique in patients with Chagas' disease. AB - The aim of this paper is to analyze the beat-to-beat variability of ventricular late potentials (LP) in high resolution ECG (HRECG) records of patients with Chagas' disease. In order to evaluate the LP activity, we propose a method which computes the bi-dimensional (2-D) cross-correlation between a template spectro temporal (STM) of LP and the STM of each individual beat of the HRECG record. As LP detection parameter, we used the maximum value of the 2-D cross-correlation multiplied by a noise correction factor. The method was applied in HRECG records of eight Chagasic patients with high myocardial damage Our results show that three patients have a low beat-to-beat variability of the detection parameter, reflecting the presence of reproducible and stable LP in their HRECG records. However, the other five patients show a high or moderate variability of the detection parameter, reflecting the possible existence of beat-to-beat variable LP. PMID- 17271072 TI - Monitoring fetal development with magnetocardiography. AB - Fetal heart rate variability (fHRV) is useful for noninvasive assessment of the status of the autonomic nervous system of the developing fetus. In this pilot study we acquired fetal magnetocardiograms (fMCG) in a magnetically shielded environment. Each recording was of 5-minute duration and was subsequently repeated in a high-frequency noise environment to examine the feasibility of conducting future recordings in clinical environments that lack facilities for magnetic shielding. The fMCG (n=17) were recorded at 9 spatial locations above the pregnant abdomen at 26 to 35 weeks gestational age (GA) by a second-order SQUID gradiometer. The signal-to-noise was adequate for reliable QRS detection even in the noisy environment, especially for GA >/= 30. The total spectral power of the RR-series, as well as band powers at low (0.05 to 0.25 Hz) and high (0.25 to 1.00 Hz) frequencies independently exhibited an increasing trend with GA. There was no evidence of bias in spectral power due to lack of shielding. These results provide experimental evidence supporting further studies in magnetically unshielded environments and may have an important implication for future clinical use of fMCG in the assessment of fHRV. PMID- 17271073 TI - Physiologic responses to acupuncture point stimulation: a pilot study to evaluate methods and instrumentation. AB - The physiological responses to needle stimulation of an acupuncture point and a nearby control point were compared in six healthy participants. The electrocardiogram (ECG), respiration, and electrodermal response (EDR) were measured along with the times of needle insertion, interim needle stimulation and needle removal. In addition to the aforementioned, any relevant events such as movement of the subject, unexpected noise, etc were annotated. PMID- 17271074 TI - Electrocardiographic characterization of embryonic zebrafish. AB - The zebrafish (Danio rerio) has emerged as one of the primary experimental models of developmental cardiovascular research. Recent progress in flow visualization techniques along with the existing genetic map of the species has made zebrafish amenable to a variety of experiments relating cardiac developmental structure and function. One essential tool in establishing the proper functioning of the heart is the electrocardiogram (ECG). This study presents a methodology whereby the ECGs of embryonic zebrafish could be used in assessing the electrophysiological consequences of genetically-, mechanically-, or pharmacokinetically-induced cardiac perturbations. Five day post-fertilization (dpf) embryos produced repeating bimodal ECGs with clearly distinguished atrial (P) and ventricular (R) depolarization waves. P-R intervals along with P-P intervals are cited. PMID- 17271075 TI - Interleukin-2 confers cardioprotection by inhibiting mitochondrial permeability transition pore. AB - In the present study, we determined whether interleukin-2 (IL-2) confers cardioprotection by inhibiting mitochondria permeability transition pore (MPTP) opening. In isolated rat hearts subject to 30 min ischemia and 120 min reperfusion (IR), IL-2 (50 U/ml) decreased the infarct size and LDH release, effects blocked by a selective kappa-opioid receptor antagonist, Nor-BNI (5 microM) or an opener of MPTP, atractyloside (Atr, 20 microM). In isolated ventricular myocytes subjected to anoxia and reoxygenation (AR), which reduced both the amplitude of the electrically induced [Ca2+]i transient and diastolic [Ca2+]i, IL-2 attenuated the AR-induced alterations and their effects were abolished by Atr. In addition, IL-2 attenuated the reduction in calcein fluorescence in myocytes subject to AR and reduced calcium-induced swelling in mitochondria of rat hearts subjected to IR, which were similar to effect of inhibitor of MPTP. The observations indicated that IL-2 confers cardioprotection by inhibiting the MPTP opening. PMID- 17271076 TI - Role of the mitochondrial permeability transition pore in TNF-alpha-induced recovery of ventricular contraction and reduction of infarct size in isolated rat hearts subjected to ischemia/reperfusion. AB - Pretreatment with tumor necrosis factor-alpha (TNF-alpha) is known to trigger cardioprotection. TNF-alpha can activate multiple downstream signaling cascades. However, it is not known whether the mitochondrial permeability transition pore (MitoPTP) is involved in TNF-alpha-induced cardioprotection. In the present study, we examined whether TNF-alpha inhibits MitoPTP opening. In isolated rat hearts subjected to 30 min regional ischemia and 120 min reperfusion, pretreatment with 10 U/ml TNF-alpha for 7 min followed by 10 min washout improved the recovery of left ventricular developed pressure (LVDP) and rate-pressure product (RPP = LVDP x heart rate) during reperfusion and reduced the infarct size. Administration of 20 micromol/L atractyloside, a MitoPTP opener, for 20 min (last 5 min of ischemia and first 15 min of reperfusion) and pretreatment with 1 mu inhibitor of the Ca2+-activated K+ mol/L paxilline, an channel, for 5 min before ischemia, attenuated the recovery of LVDP and RPP and the reduction of infarct size induced by TNF-alpha. The findings indicate that, in the isolated heart model, TNF-alpha protects myocardium against ischemia/reperfusion injury via inhibiting MitoPTP opening as well as by activating the Ca2+-activated K+ channel. PMID- 17271077 TI - The mitochondrial calcium uniporter participates in ischemia/reperfusion injury and in cardioprotection by ischemic preconditioning. AB - The objective of the present study was to determine whether the mitochondrial calcium uniporter plays a role in cardioprotection by ischemic preconditioning (IPC). Isolated rat hearts were subjected to 30 min regional ischemia by ligation of the left anterior descending artery followed by 120 min reperfusion. We found that both IPC and inhibition of the mitochondrial calcium uniporter during reperfusion improved recovery of left ventricular developed pressure, maximal rise velocity and end-diastolic pressure, and reduced infarct size and lactate dehydrogenase release. These protective effects were attenuated by activating the mitochondrial calcium uniporter. We conclude that the mitochondrial calcium uniporter is involved in the cardioprotection of ischemic preconditioning. PMID- 17271078 TI - Effects of interleukin-2 on the mechanical restitution and post-rest contraction in rat ventricular papillary muscle. AB - To determine whether application of interleukin-2 (IL-2) alters function of sarcoplasmic reticulum (SR), we measured mechanical restitution and post-rest potentiation (PRP) in isolated rat papillary muscles. Mechanical restitution curves were constructed by interpolating extrasystoles at different test intervals following a train of steady state beats. In control group, the maximal PRP was reached after 60-120s of rest and the maximal potentiation factor was 2.36 +/- 0.23. IL-2 at 200 U/ml decreased the steady-state force of contraction to 56.4 +/- 7.2% of pre-drug control. But the time constant of recovery of steady state force was not altered after IL-2. IL-2 decreased PRP at all intervals, shifted the potentiation curve parallel to lower values. But the potentiation was enhanced when compared with pre-rest control value in the presence of IL-2. In papillary muscle treated with IL-2, the onset of maximal PRP was delayed and the potentiation factor after 300s was 4.72 +/- 0.58 times that at the steady-state. Recirculation fraction of calcium calculated from the decay of PRP was 0.78 +/- 0.09 in control and 0.59 +/- 0.08 after IL-2 treatment. We conclude that IL-2 decreases the function of SR, which suggests that an impaired function of SR may contribute to the negative inotropic effect of IL-2. PMID- 17271079 TI - Negative inotropic effect of interleukin-2 in the isolated ventricular myocytes: role of NO/sGC pathway. AB - The present study is to investigate the effect and possible mechanism of interleukin-2 (IL-2) on the cell contractility in isolated rat cardiomyocytes. Ventricular myocytes were isolated from adult male Sprague-Dawley rats. Contractile responses were evaluated by use of the video tracking system. Contractile properties analyzed in cells electrically stimulated at 0.2Hz included peak velocity of cell shortening (+dL/dtmax), peak velocity of cell relengthening (-dL/dtmax), contraction amplitude (dL) and end-diastolic cell length. Calcium transients of ventricular myocytes were determined by the spectrofluorometric techniques. IL-2 (2.0, 10, 50, 200 and 1000 U/ml) exhibited a dose-dependent inhibition in +dL/dtmax, -dL/dtmax, dL and end-diastolic cell length. Pretreatment with the nitric oxide synthase inhibitor Nomega-nitro-L arginine methyl ester (L-NAME, 100 microM) and 1H [1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ, soluble guanylyl cyclase inhibitor) blocked IL-2-induced inhibition of the contractility. IL-2 at 200 U/ml decreased the amplitude of the [Ca2+]i transient. Pretreatment with the L-NAME or ODQ abolished IL-2-induced inhibition of amplitude of the calcium transient. We conclude that the depressant effect of IL-2 on the contraction and calcium transient of isolated ventricular myocytes is mediated by nitric oxide/soluble guanylyl cyclase pathway. PMID- 17271080 TI - Hemodynamic interventions and the pressure-diameter loop of the left ventricle and the proximal aorta in the conscious dog. AB - The dynamics of the left ventricle (LV) have been extensively investigated. However, most studies refer to steady state conditions. We addressed the beat-to beat variations resulting from hemodynamic interventions analyzed in the chronically instrumented dog. This approach permits serial studies in the same subject under physiological conditions. In particular we investigated the end systolic pressure-dimension relationship and characteristics of the proximal aorta. The findings obtained during basal conditions, exercise and pharmacologic intervention indicate that several universal regulatory mechanisms are involved, besides various phenomena that exhibit a substantial degree of variability. PMID- 17271081 TI - Cardiac parametric variations in post-ischemic myocardium. AB - Mechanisms governing post-ischemic ventricular function after episodes of acute myocardial ischemia are still unclear. We investigated this stunned myocardial function with a computer model in conjunction with animal experiments. A modified lumped cardiac muscle model was subjected to parametric changes similar to regionally recorded ventricular parameters. The model was perturbed by alterations in contractility and rates of activation and deactivation. Results show that the cardiac muscle model can mimic many of the physiological changes observed in a stunned myocardium. PMID- 17271082 TI - A Kalman filtering approach to estimation of maximum ventricle elastance. AB - In this paper a method for estimating maximum ventricular elastance through an extended Kalman filter is proposed, based on measurement of ventricular volume and aortic pressure. The Kalman filter is particularly well suited to this task, since it produces an optimal estimate (in the sense that the error is statistically minimized) given noise corrupted data. The EKF model is derived from an electrical-analog model of the left ventricle and systemic load. An observability study was a priori conducted on the model, restricted to the ejection phase, to validate the estimation procedure. The method has been evaluated with simulated data and produced good results (the estimate error was 7.14%). PMID- 17271083 TI - Computing work in the ischemic heart. AB - This study analyzes the effect of a poorly perfused (ischemic) region on active tension and strain at a point in a model of the cardiac ventricles. The cellular active mechanics and electrophysiology were calculated using a coupled electromechanical cell model. The deformation of the heart was calculated combining an anisotropic constitutive law with the active tension generated by the cell models. An ischemic cell model was developed by adapting the Noble 98 HMT cell model parameters. The ischemic model exhibits a raised resting potential, shortened action potential duration and reduced amplitude. Ischemic cells were introduced into the heart model in the anterior wall of the left ventricle. The model was solved with and in the absence of the ischemic region. The stress and strains at a point located in the ischemic region were calculated. The ischemic cell model produced negligible amounts of active tension and this reduced the work load of ischemic cells by several orders of magnitude. The ischemic region had a significant effect on pump function in both the left and right ventricles. PMID- 17271084 TI - Frequency-based analysis of diastolic function: detrimental phase-shift of the pressure-flow relation characterizes the 'delayed relaxation'; transmitral flow pattern. AB - Cardiologists assess the filling (diastolic) function (DF) of the heart by visually determining whether Doppler echocardiographic transmitral E-waves appear to have "normal", "delayed-relaxation" or "constrictive restrictive" patterns. To achieve a causal method of quantitative DF assessment we present a frequency based approach. In analogy to impedance of electrical circuits, we characterize DF by analysis of the left ventricular (LV) diastolic pressure (P) to transmitral flow (Q) relation during the Doppler E-wave in the frequency domain in terms of Z(omega) = P(omega) / Q(omega), characteristic and input impedance. This allows DF to be expressed in terms of a complex reflection coefficient R* =/R*/e(iphi). Twenty subjects had simultaneous pressure-flow data recorded during catheterization, were dichotomized according to deceleration time (DT) and had E waves subjected to model-based image processing (MBIP) to determine model parameter c, related to E-wave deceleration. Results show that phase angle phi is linearly related to c ; that both phi and c were significantly different (p < 0.05) between the short (n=12) and long (n=8) DT group. We conclude that the 'delayed relaxation'; pattern is associated with deviation of the phase angle phi from its optimal (pi) value that minimizes reflection and maximizes filling, resulting in modification of the optimal pressure - flow relation in early diastole. PMID- 17271085 TI - Evaluation of isovolumic relaxation phase in the process of ventricular remodeling following myocardial infarction. AB - The course of cardiac remodeling after an acute cardiac MI, might affect the orientation of the cardiac muscle fibers as well as their contraction behavior. This may result in alteration of the untwisting during isovolumic relaxation phase, which might have effects on rapid early filling phase. In the present article, the variation of the time constant of isovolumic pressure drop (tau) has been studied during the course of cardiac remodeling after different types of induced myocardial infarction (MI) in sheep. The results for each group show different patterns of change in tau. The normalized tau curve in all three groups of anteroapical, anterobasal and posterobasal MI group show a rise 30 minutes after infarction. Two weeks later, the pressure drop constants decline to a lower level than baseline and by eight weeks after infarction, the time constant reached around the baseline level. PMID- 17271086 TI - Model generation interface for simulation of left ventricular motion. AB - Recent advances in constructing accurate cell models have enabled new research areas for establishing accurate tissue and organ models. One important target of such research is heart. However, although the accurate myocardial cell model is becoming available, many elements such as cell orientation, mechanical tissue properties are still not known. On the other hand, computer simulation is becoming important tool for biological research. In such research, biological model is constructed and evaluated with variety of parameters. However, for the organ models such as heart model, it becomes very complicated and difficult to generate and evaluate variety of heart models with different combinations of element models and their parameters. In this paper, we propose an interface which generates complex left ventricular simulation model. We can generate left ventricular simulation models with 3D shape model, cell orientation model, cell electrophysiological model, coronary artery model and tissue mechanical property and model. Obtained simulation results show the effectiveness of the system. PMID- 17271087 TI - Intracardiac echocardiographic measurement of left ventricular volume. AB - We tested the utility of intracardiac echocardiography (ICE) in measuring left ventricular (LV) volume. In 4 normal dogs, a 10-F percutaneous sheath was placed inside the LV along its major axis. An ICE catheter (9 F, 9 MHz) was then inserted through the sheath into the LV. The ICE catheter was pulled back in 1-mm intervals starting from the apex, and 2-D tomographic images were continuously acquired. Subsequently, the ICE catheter was replaced in the LV by a conductance catheter to measure single-beat volume signals. Stroke volume was determined by thermodilution for validation. All measurements were made in each dog while pacing the atrium at two different cycle lengths (range=300-500 ms). The endocardium was segmented in the ICE images throughout the cardiac cycle, and LV volume was computed by integrating multiple segments (range=55-70 mm). We found that ICE accurately reconstructed LV 3-D anatomy. Stroke volume by ICE was in excellent agreement with thermodilution (error = 3.8+/-3.0%, r = 0.99, n = 8). Morphology of LV volume signals correlated well with instantaneous volume signals derived by conductance (r=0.93, n=8). In conclusion, ICE accurately reconstructs LV anatomy and volume throughout the cardiac cycle in the normal heart. This approach could facilitate interventional diagnostic and therapeutic procedures. PMID- 17271089 TI - Construction of the global lagrangian strain field in the myocardium using DENSE MRI data. AB - The main aim of this study is to generate global strain maps within the myocardial wall. Transmural strain calculations are performed using DENSE MRI data, acquired in a long-axis plane for canine subjects over the complete cardiac cycle. Continuum mechanics formulations were applied to all segments of the myocardium and later analyzed from anatomical and physiological perspectives. Characteristic parameters of the myocardial wall - namely global strain distributions - were quantified by means of numerical analyses of DENSE MR data. Our study demonstrated the initiation of myocardial strain as well as heterogeneous contraction patterns across the ventricle wall. There were measurable wall shear strains throughout the cardiac cycle, with the maximum strain within the long-axis plane concentrated in the septal wall at the start of systole and later becoming more pronounced in the lateral wall in the diastolic period. The methods described will lead to a better understanding of the complex myocardial contraction from these space- and time-resolved data on wall motion. PMID- 17271088 TI - Regional differences in systolic active stress profiles in the normal beating heart. Assessment using an ultrasound based mathematical model. AB - Active stress (sigmaA) developed by cardiac muscle has been measured in isolated muscle preparations, under physiological loading conditions, by subtracting the passive stress (sigmaP) from the total stress (sigmaT). We previously developed a mechanical model based on M-mode ultrasound imaging to calculate these stresses in beating hearts. However, this model was based on one-dimensional imaging information and could not estimate regional differences in sigmaA. In the current study this model was improved by including two-dimensional B-mode echocardiographic data. METHODS: In a porcine model a micro-manometer tipped catheter was used to measure left-ventricular pressure (LVP) and B-mode ultrasound images were recorded in a short-axis view. On the ultrasound image points in the mid-wall were selected and tracked to completely define the deformation of the myocardium. A kinematic model of the LV was then constructed from the displacement vectors of these points. sigmaT was calculated from the LVP. The material parameters for an exponential stress/strain relation were estimated during the diastolic E-wave when it was assumed that sigmaA = 0. These parameters were used to calculate sigmaP during systole and by subtracting this from sigmaT, sigmaA was calculated. RESULTS: The timing and shape of sigmaA profiles match those obtained from isolated muscle experiments. SigmaA was higher and peaked sooner in the posterior wall than in the anterior wall. CONCLUSION: Regional active stress estimation is possible in normal beating hearts. PMID- 17271090 TI - Evidence of time-varying myocardial contribution by in vivo magnitude and phase measurement in mice. AB - Cardiac volume can be estimated by a conductance catheter system. Both blood and myocardium are conductive, but only the blood conductance is desired. Therefore, the parallel myocardium contribution should be removed from the total measured conductance. Several methods have been developed to estimate the contribution from myocardium, and they only determine a single steady state value for the parallel contribution. Besides, myocardium was treated as purely resistive or mainly capacitive when estimating the myocardial contribution. We question these assumptions and propose that the myocardium is both resistive and capacitive, and its contribution changes during a single cardiac cycle. In vivo magnitude and phase experiments were performed in mice to confirm this hypothesis. PMID- 17271091 TI - Hemodynamic simulation of vascular prosthesis altering pulse wave propagation. AB - Potential clinical application of a computer model of the aorta was investigated to study the influence on pulse wave morphology of vascular prosthesis. Ascending aorta, aortic arch and abdominal aorta were replaced with synthetic graft materials and profiles. Geometric and compliance mismatch of the synthetic graft sections replacing part of the natural vessel resulted in alterations of the pulse waveform. These changes in pressure and flow waveforms were compared to investigate their effects on the vascular system for both the uniform and tapered vessel models. PMID- 17271092 TI - One important area gradient force has been omitted in the Moens and Korteweg's Equation. AB - Pulse wave velocity is mostly related to the young's modulus by the Moens and Korteweg's formula. In deriving this formula, the wall's effect on the blood was ignored at the first step and the pressure gradient was considered as the only driving force in the axial flow of the blood. The local area gradient was assumed to be zero. However, for a real arterial system with compliance, the area gradient is automatically accompanied with the pressure gradient and it will contribute an area gradient force. This force has been omitted so far without any justification because it will contribute a nonlinear term and also leads an obstacle for the analogy with the transmission line theory. We give a quantitative evaluation of the ratio of the area gradient force to the pressure gradient force and find that it is more than 50% in the main artery. This shows the inadequacy and the inaccuracy of the pulse wave velocity derived based on this axial flow equation. We propose that starting from the radial equation of motion might provide an alternate, feasible method to study hemodynamics by energy concern. PMID- 17271093 TI - Measurement of pulse wave velocity using magnetic resonance imaging. AB - Arterial stiffness has a strong relationship with cardiovascular disease. Pulse wave velocity (PWV) is increasingly used as a measure of arterial stiffness. The calculation of PWV requires accurate measurement of blood flow velocity and aortic length. Using magnetic resonance imaging (MRI), we are able to accurately acquire blood flow velocity and to virtually measure the aortic length inside the central aorta. Manual measurement of aorta length is inaccurate and subjective. In this study, we set out to develop a method which automatically locates the thoracic aorta and measures aortic length, allowing noninvasive measurement of PWV derived from the aortic flow. Our method is novel, efficient and robust. This offers a reliable and convenient tool for PWV measurement allowing detailed non invasive assessment of cardiovascular risk. PMID- 17271094 TI - Noninvasive ultrasonic measurement of arterial wall motion in mice. AB - To facilitate assessment of arterial function, we developed a noninvasive Doppler method for measuring vessel motion in genetically altered mice. A 20 MHz probe was held by an alligator clip and positioned over the carotid arteries of 16 mice including six 3 to 5-month old wild-type (WT), four 30-month old senescent (Old), two apolipoprotein-E (ApoE), and four alpha smooth muscle actin (alphaSMA) mice. Doppler signals were obtained simultaneously from both vessel walls and from blood flow using one or two probes. The displacement signals from the near and far walls were subtracted to generate a diameter signal from which the excursion and an augmentation index were calculated. The excursion ranged between 13 microm (in ApoE) and 95 microm (in alphaSMA). The augmentation index was lowest in the WT mice (0.06) and highest in the Old mice (0.29). This noninvasive method is able to identify and confirm characteristic changes in arterial properties associated with age, atherosclerosis, and the absence of vascular tone. PMID- 17271095 TI - A two-layer model of the static behaviour of blood vessel walls. AB - A model is presented that simulates the steady state two-layer nature of blood vessel walls. The model comprises an intimal-medial layer and an adventitial layer, both of which are modeled using previously validated separate models. By including both models, different types of blood vessel can be modeled within a common framework. The necessary relationships that link the two models are presented and simulations of the complete model shown. These illustrate how different types of vessel exhibit different non-linear behaviour. The models include both mechanical and biochemical aspects of the vessel wall behaviour, which will enable the model to be used to simulate more advanced behaviour such as local autoregulatory processes. PMID- 17271096 TI - Blood flow through axially symmetric sections of compliant vessels: new effective closed models. AB - Due to a tremendous complexity of the human cardiovascular system it remains unfeasible to numerically simulate larger sections of the circulatory system using the full three-dimensional (viscous, incompressible Navier-Stokes) equations for blood flow in compliant vessels. Several "effective" one dimensional models have been used to simplify the calculation in the axially symmetric sections. All of the one-dimensional models assume an ad hoc axial velocity profile to obtain a closed system of equations, and the Law of Laplace (the independent ring model) to model the vessel wall behavior. In this work we obtain an effective system of equations with the following two novel features: (1) the effective equations do not require an ad hoc closure assumption (the closure follows from the analysis of the original three-dimensional equations) and (2) the vessel wall is modeled as a nonlinearly elastic shell using the Koiter model or the nonlinear membrane model. The first novelty provides a higher order accurate solution to the original three-dimensional problem, and the second allows deformations of the vessel wall that are not necessarily small. PMID- 17271097 TI - Optimal lymphatic vessel structure. AB - Lymphatic vessels transport excess interstitial fluid from the low-pressure tissues to the higher pressure veins. The basic structural unit of lymphatic vessels is the lymphangion, a segment of the vessel separated by two unidirectional valves. Lymphangions cyclically contract like ventricles and can actively pump lymph. Lymphangions, as conduit vessels, also can act as arteries, and resist lymph flow. Functional parameters such as pressures, flow, and efficiency are determined by structural parameters like length, radius, and wall thickness. Since these structural parameters are unalterable experimentally, we developed a computational model to study the effect of a particular structural parameter, lymphangion length, to a particular functional variable, lymph flow. The model predicts that flow is a bimodal function of length, exhibiting an optimal length in the same order of magnitude as that observed experimentally. In essence, when the length to radius ratio is small, lymphangions act more like ventricles, where longer lengths yield greater chamber volume and thus lymph pumped. When the length to radius ratio is large, lymphangions act more like arteries, where longer lengths yield greater resistances to flow. This approach provides the means to explore how lymphatic vessel structure is optimized in a variety of conditions. PMID- 17271098 TI - Doppler ultrasound determination of the distribution of human cardiac output: effects of age and physical stresses. AB - Due to its high spatial, temporal, and dynamic resolution, noninvasive Doppler ultrasound can be used to determine the distribution of phasic cardiac output in humans. The effects of ageing and various common physical stresses on combined human major central and regional blood flows have not been reported. We tested the hypothesis that there are no significant age-related differences in steady state human central and regional hemodynamics during leg exercise, hypoxia, eating, and standing. We used noninvasive, image-guided Doppler flowmetry (approximately 7% linearity, approximately 11% accuracy) to measure absolute values and percent changes (%C) in phasic blood flows in the following major arteries: ascending aorta (CO, cardiac output), common carotid (CQ, brain), subclavian (SQ, arm), renal (RQ, kidney), superior mesenteric (MQ, gut), and common femoral (FQ, leg). Mean arm cuff blood pressure (BP), heart rate (HR), stroke volume (SV), and total peripheral resistance (PR) were also determined. We studied 16 young (Y, 24/3 years, 8 males) and 16 elderly (E, 73/2 years, 7 males) healthy, lean adults during separate experiments of: 50% submaximal leg exercise; 12% oxygen breathing; ~700 calorie meal; and 70 degrees upright tilt. Exercise results (X/SD) are given as Y(%C) then E(%C) where (+) represents p<0.05 vs resting, fasting control: HR: 78/8+,66/7+; BP: 6/5,8/6; SV: - 15/5+,21/4+; CO: 96/11+,87/9+; PR: -83/13+,- 76/10+; CQ: 16/8+,14/6+; SQ: -6/8,-12/8; MQ: -21/11+, 15/11; RQ: -14/8/-12/7; FQ: 919/88+,898/74 Importantly, there were no significant (p<0.05) age-related differences in the percentage changes in any of these hemodynamic variables. Similar results were found during hypoxia, eating, and standing. We conclude that although physical stresses significantly (p<0.05) affects various central and regional hemodynamics, there are no significant age related differences in these variables between healthy, successfully aged, 20 and 70 year old cohorts. These data suggest that given an appropriate genetic template and behavior free of significant trauma and disease states, cardiovascular control mechanisms and the distributions of cardiac output during common, daily, physical stresses are maintained with age through 70 years of life. PMID- 17271099 TI - Variations of the maximum blood flow velocity in the carotid, brachial and femoral arteries in a passive postural changes by a Doppler ultrasound method. AB - We have developed a blood flow velocimeter to measure maximum blood flow velocity (MBFV) in carotid, brachial and femoral arteries simultaneously by using a Doppler ultrasound technique. This measurement system is based on a continuous wave Doppler ultrasound method with two semicircular piezoelectric (PZT) transducers, one continuously transmitting ultrasound, and the other continuously receiving the echoes. This report is to investigate variations of MBFV in 3 arteries of 5 healthy normal male volunteers during passive postural changes in supine, 90 degrees head-down-tilt (HDT) and 90 degrees head-up-tilt (HUT) respectively. As a result of these measurements, we could confirm that MBFV in those arteries especially in brachial and femoral are increased by supine to HDT posture and are decreased by supine to HUT posture. But, it's just changed a little in carotid artery. An increasing and a decreasing in MBFV are expected to be an effect of venous pressure and a constant MBFV in carotid artery is caused a cerebral autoregulation. PMID- 17271100 TI - Cardiac output monitoring in intensive care patients by radial artery pressure waveform analysis. AB - We have developed a novel technique for monitoring cardiac output (CO) changes by mathematically analyzing a single peripheral arterial blood pressure (ABP) waveform. In contrast to all previous techniques, our technique analyzes the ABP waveform over time scales greater than a cardiac cycle in which complex wave reflections are attenuated. We have previously validated the technique in swine instrumented with aortic flow probes. We present here an initial evaluation of the technique in 16 patient records of the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) database, consisting of 122 simultaneous pairs of radial ABP waveforms and thermodilution CO. We report an overall error in the technique of 18.1% with respect to the error-prone clinical thermodilution measurements. This study promotes thorough future testing of the technique in humans. PMID- 17271101 TI - A comprehensive physiological model of circulation enables automatic piloting of hemodynamics in patients with acute heart failure. AB - A comprehensive physiological model of the whole circulation is mandatory to quantitatively diagnose pathophysiology and to guide an appropriate treatment. Such a model would enable automatic piloting of hemodynamics in patients with acute heart failure. By extending Guyton's model, so as to deal with heart failure predominantly affecting left heart and to quantify left atrial pressure, we constructed such a model consisting of a venous return (VR) surface and a cardiac output (CO) curve. VR surface, the integrated property of systemic and pulmonary vascular beds, relates VR and left and right atrial pressures (P(LA), P(RA)) linearly as VR = V/W - G(R)P(RA) - G(L)P(LA), given total blood volume (V). CO curve, the pumping ability of hearts, relates CO and either P(LA) or P(RA) approximately by logarithmic functions, respectively, as CO = S(L) [ln (P(LA)- B(L)) + C(L)] = S(R) [ln (P(RA) - B(R)) + C(R)]. The slopes (S(R) and S(L)) of CO curve mainly describes the pump performance. W, G(R), G(L), B(R), B(L), C(R) and C(L) are parameters. We validate the model with animal experiments. Parameters W, G's, B's and C's were relatively constant in 19 dogs. In other 8 dogs, with or without acute left heart failure, we determined V and S's from a single set of CO, P(RA), P(LA) and standard parameter values. We then predicted hemodynamics (CO, P(RA), P(LA)) for altered V from -8 to +8 ml/kg. We identified standard values of parameters as W (0.13 min), G(R) (19.6 ml/min/kg/mmHg), G(L) (3.5 ml/min/kg/mmHg). B(L) (2.1 mmHg), C(L) (1.9), B(R) (2.0 mmHg) and C(R) (0.80). Using these, we could accurately predict CO (y = 0.93x + 6.5, r2 = 0.96, Figure 2), P(RA) (y = 0.87x + 0.4, r2 = 0.91) and P(LA) (y = 0.90x + 0.48, r2 = 0.93). Our comprehensive physiological model of circulation is useful in accurately predicting hemodynamics from the measurement of a single set of CO, P(RA) and (P(LA) following blood volume changes. Therefore, this model enables continuous monitoring of blood volume and pump performance for automatic hemodynamic piloting. PMID- 17271102 TI - Effect of cellular elements on pressure-velocity relationship in mice. AB - The effect of cellular elements in the blood on peripheral vascular function in mice was evaluated using the pressure-velocity relationships in the iliac arteries of 5 wild type (WT) and 3 polycythemic (MH) mice. Pressure was obtained using a fluid filled catheter in the left iliac artery and blood velocity was measured in the right iliac artery using a 20 MHz pulsed Doppler probe. The proximal aorta was then occluded for one minute to allow flow velocity to decay to zero. The pressure-velocity relationship in the diastolic phase was determined before and after aortic occlusion. In both groups the pressure-velocity relationship was almost linear and the slopes were similar. However, the extrapolated zero-velocity intercept was significantly higher for the MH than WT mice before (55.4 +/- 4.0 vs. 36.2 +/- 4.1 mmHg, p<0.01) and after occlusion (50.7 +/- 5.5 vs. 23.8 +/- 3.1 mmHg, p<0.01). Hematocrits were 41%+/-3 in WT and 59%+/-3 in MH mice. These data show that cellular elements in the blood alter the pressure-velocity relationships in peripheral vessels of mice. PMID- 17271103 TI - Method for the measurement of the sensitivity of vascular beds to ischemia. AB - We identify a novel performance parameter of arterial beds and propose a convenient, non-invasive method for its measurement. The parameter relates the amount of reactive hyperemic flow that ensues after blood flow occlusion to the duration of occlusion and thus may be viewed as a measure of the sensitivity of the downstream vascular bed to the level of ischemia. The measurement is performed by inducing three successive progressively longer periods of ischemia in a limb using a pneumatic cuff. During the periods between occlusions, reactive hyperemic flow is measured at a finger using laser Doppler fluximetry (LDF). Total hyperemic response is calculated for each occlusion by averaging the LDF time series over the interocclusion interval. The vascular sensitivity parameter is calculated as the gradient of the line fit to the three mean response measurements. We evaluate the method in 18 subjects and find that orally administered nicotine significantly reduces the sensitivity to ischemia by 34%. PMID- 17271104 TI - Mechanics of the mitral valve: in vitro studies. AB - Improved knowledge of mitral valve (MV) mechanics is essential to understanding normal MV function and design; however, there is limited information about the mechanical properties of the MV during physiologic loading. These studies utilized different techniques to characterize the mechanical properties of the MV. Histological techniques were used to examine collagen, elastin, and cellular distribution on the chordae. Vessels were observed in both the longitudinal and circumferential directions. The presence of vessels characterize the chordae as complex living components that must work with the PM and MV leaflets to prevent MV prolapse and regurgitation. Force and strain distribution on the chordae and anterior leaflet were measured in a pathological papillary muscle (PM) positions. Tension distribution results showed that the intermediate chords on their respective leaflets. The slack PM position led to a delay in complete valve closure and more rapid leaflet loading in late systole. The chordae showed physiological strains, reaching maximum strain during valve closure. The in vitro studies demonstrated that chordal force distribution and valve function depend on the mechanical environment of the valve and the geometric relationships between its components. PMID- 17271105 TI - Development of markers of valve stiffness for prediction of hemodynamic progression of aortic stenosis. AB - Degenerative aortic valve stenosis is a progressive disease with an unpredictable rate of progression. Early changes in the degenerative process include thickening and stiffening of the leaflets, reflected in altered rates of opening and closing. Methods have been proposed to measure this in vivo and relate it to the rate of disease progression. In this in vitro study, we tested the hypothesis that changes in ambient hemodynamics that might contribute to the wear and tear process that mediates the degenerative process affect valve mechanics, and that this is reflected in the rates of valve opening and closing. Evidence supporting this hypothesis is presented and an alternative method to account for these effects is proposed. PMID- 17271106 TI - A structural constitutive model for the native pulmonary valve. AB - Replacement of the native pulmonary valve (PV) with tissue engineered valves requires a thorough understanding of the function of the PV. We undertook the following study to quantify the biaxial mechanical behavior of the porcine PV and develop a structural constitutive model. To our knowledge, this is the first such model for the PV. PMID- 17271107 TI - Fibrotic vs. myxomatous remodeling of mitral valves. AB - Heart valves respond to load patterns imposed during valve function by remodeling their microstructure and matrix components. When exposed to loading or geometry outside of its normal range, the valve will remodel. We performed mechanical testing and biochemical analysis of extracellular matrix to compare normal mitral valves with valves that had remodeled due to primary or secondary valve disease. One form of remodeling we found was a fibrotic change, characterized by disorganized collagen produced to withstand high tensile loads. This remodeling occurred in congestive heart failure, in which the mitral valves were significantly less extensible, stiffer, and less viscous than autopsy control valves. These material changes were accompanied by higher cell and collagen concentrations as well as less water. We found a different type of remodeling in myxomatous mitral valves, in which abnormally low tensile loading results in the accumulation of glycosaminoglycans (GAGs). Myxomatous valves were more extensible, less stiff and strong, and contained more water and the GAGs hyaluronan and chondroitin 6-sulfate than normal mitral valves. Thus, valves that experience higher tensile loads than normal exhibited fibrotic scarring and stiffening, while valves with reduced normal loading demonstrated a degenerative edematous change with high extensibility and low strength. PMID- 17271108 TI - Skewness angle of interfibrillar proteoglycan increases with applied load on chordae tendineae. AB - In highly aligned connective tissues, such as tendon, collagen fibrils are linked together by proteoglycans (PGs). We used transmission electron microscopy to observe the collagen fibril-proteoglycan interactions in porcine mitral valve chordae under loaded conditions. Comparison of fibril-proteoglycan configuration between stressed and load-free states showed that PGs mainly attached to collagen fibrils perpendicularly in the load-free situation, and became skewed when the chordae were loaded. The average skewness angle of PGs increased with the applied load. The observation of skewed proteoglycans demonstrated that interfibrillar slippage occurs in chordae, and that proteoglycans might play a role in the fibril-to-fibril interaction. PMID- 17271109 TI - Modelling chorded prosthetic mitral valves using the immersed boundary method. AB - The Immersed Boundary (IB) Method is an efficient method of modelling fluid structure interactions. However, it has two main limitations: ease of use and ability to model static loading. In this paper, the method is developed, so that it can efficiently and easily model any multileaflet elastic structure. The structure may include chordae, which attach to the leaflets and continue through the leaflet surfaces. In addition, an external surface pressure may be applied to the leaflets, thus enabling the deformations that arise under steady loads to be solved. This method is validated for a model of the native mitral valve under systolic loading and for a prosthetic aortic valve under static loading. It is then applied to a new chorded prosthetic mitral valve, housed in a cylindrical tube, subject to a physiological periodic fluid flow. Results are compared with those obtained by using the commercial package ANSYS as well as with experimental measurements. Qualitative agreements are obtained. There are some discrepancies due to the current IB method being unable to model bending and shear behaviour. In particular, the fibre structures of the new prosthetic valve model developed using the IB method may be prone to crimping. Further development of the IB method is necessary to include bending effects. This will improve the accuracy of both the dynamic and static analysis. PMID- 17271110 TI - Parameter estimation by descent and genetic algorithm methods of an in-vitro stenosis bypass model. AB - The development of improved hemodynamic impedance models can greatly aid the understanding of arterial disease progression and its remediation. This paper leverages the recent progress in advanced manufacturing techniques to engage in in-vitro experimentation with physiologically relevant geometries and flows that correspond to arterial stenosis. The measurements of pressures and flow obtained by these experiments were then used to estimate flow-to-pressure transfer functions, aimed at determining a lumped-parameter impedance model of the physical system, by applying conventional descent as well as recently developed Genetic Algorithm methods. The resulting transfer functions can now be utilized for further studies with regard to the hemodynamics relevant to arterial stenosis. PMID- 17271111 TI - Endothelium-independent vasorelaxant effect of lidocaine in rat aortic rings. AB - In the present study, lidocaine relaxed, in a concentration-dependent manner, the contractions induced by either phenylephrine or a high concentration of KCl (60 mM) in endothelium-intact rat aortic rings. Mechanical removal of endothelium did not significantly modify lidocaine-induced vasorelaxation. In endothelium-denuded aortic rings depolarized by 60 mM KCl, lidocaine inhibited Ca2+-induced contraction. Lidocaine also reduced the transient contraction elicited by phenylephrine in Ca2+-free medium. Pretreatment of endothelium-denuded aorta nonspecific K+ with tetraethylammonium, a channel blocker, had no effect on the relaxant effect of lidocaine. These results indicate that lidocaine induces an endothelium-independent relaxation in rat aortic rings. The main mechanisms may include suppression in Ca2+ through the voltage-sensitive Ca2+ influx intracellular Ca2+ channels and inhibition of release in the vascular smooth muscle cells. PMID- 17271112 TI - Endothelium-independent vasorelaxant effect of puerarin on rat thoracic aorta. AB - To investigate the vasorelaxant effect of puerarin, tension was recorded from rat thoracic aortic rings. Puerarin completely relaxed the contractions induced by phenylephrine (PE) in a concentration-dependent manner in endothelium-intact and endothelium-denuded rat aorta, while had no effect on those preconstricted by a high concentration of potassium chloride (60 mM). Also, puerarin had no effects on the transient contraction elicited by PE or caffeine in Ca2+- free medium. The relaxant effect of puerarin was significantly inhibited by pretreatment of endothelium-denuded aorta with potassium channel antagonists tetraethylammonium and 4-aminopyridine, but not glibenclamide. These results indicate that puerarin induces an endothelium-independent relaxation in rat aortic rings. The mechanisms may involve the reduction in Ca2+ influx through the non-voltage-sensitive calcium channels and the activation of the potassium channels (voltage-activated K+ channels and large conductance Ca2+ -activated K+ channels, but not ATP sensitive K+ channels). PMID- 17271113 TI - Hemodynamic and left ventricular pressure-volume responses to counterpulsation in mock circulation and acute large animal models. AB - Alternative therapies for treating heart failure patients are being explored to provide effective options for patients with progressive heart failure. Cardiac assist devices that promote myocardial recovery may be a potential solution. Ventricular assist devices (VAD) have demonstrated long-term efficacy and intraaortic balloon pumps (IABP) have shown short-term successes. In this paper, testing of a hybrid counterpulsation device (CPD) that couples the attributes of device longevity (VAD) with less invasive surgery (IABP) is presented. Hemodynamic and ventricular pressure-volume responses to a 40 ml CPD and 40 ml IABP were evaluated in vitro in an adult mock circulation and in vivo in a large animal heart failure model. The CPD is a flexing diaphragm ventricle with a controlled stroke volume up to 85 cc through a single, valveless cannula. In this study, the CPD was cannulated to the brachiocephalic artery to provide 40 ml of counterpulsation support. The CPD effectively provided diastolic augmentation increasing coronary flow and afterload reduction. These results were comparable to IABP. These preliminary studies suggest that CPD may be an effective therapy for treating patients with early stage heart failure. PMID- 17271115 TI - An architecture for rapid prototyping of control schemes for artificial ventricles. AB - This paper presents an experimental system aimed at rapid prototyping of feedback control schemes for ventricular assist devices, and artificial ventricles in general. The system comprises a classical mock circulatory system, an actuated bellow-based ventricle chamber, and a software architecture for control schemes implementation and experimental data acquisition, visualization and storing. Several experiments have been carried out, showing good performance of ventricular pressure tracking control schemes. PMID- 17271114 TI - Recent progress of moving-actuator type mechanical circulatory support systems: AnyHeart and T-PLS. AB - The mechanical circulatory support system using moving-actuator mechanisms were developed by Seoul National University and Korea University. AnyHeart is a fully implanted pulsatile bi-ventricular assist device, and T-PLS is a pulsatile flow versatile extracorporeal life support system. Through lots of in-vitro and in vivo experiments, the developed mechanical systems are faced to produce on commercial scale. This paper describes the recent progress of two mechanical circulatory support systems, AnyHeart and T-PLS. PMID- 17271116 TI - In vitro evaluation of control strategies for an artificial vasculature device. AB - Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. An artificial vasculature device (AVD) that may better facilitate myocardial recovery than VAD by controlling the afterload seen by the ejecting heart is being developed. The AVD concept is to enable any user-defined input impedance (IM) with resistance (R) and compliance (C) components. In this study, a pulse duplicator was used to test the efficacy of the AVD concept for two control strategies in an adult mock circulation: (1) R-C in series and (2) 2 element Windkessel (R-C in parallel) using instantaneous impedance position control (IIPC) to maintain a desired value or profile of R and C. In vitro experiments were performed and the resulting cardiovascular pressures, volumes, flows, and the afterload (R and C) seen by the LV during ejection for simulated cardiac failure were recorded and analyzed. Our results indicate that setting the AVD to lower IM reduced LV volume and pressure, restored LV stroke volume, and increased coronary flow. The IIPC control algorithms are better suited to maintain any instantaneous IM or an IM profile, but are susceptible to measurement noise. PMID- 17271117 TI - Dynamic response of the pulmonary circulation in continuous flow artificial heart systems. AB - Pulmonary circulation dynamics is important when considering bi-ventricular assist devices (BiVAD) or total artificial heart (TAH) systems and in investigating the mechanism of atrial collapse in order to design better control algorithms. In this study, we investigated pulmonary circulation dynamics in a continuous flow artificial heart system by performing acute tests on a mature goat. By varying the right pump speed, we were able to observe the dynamic response of the left atrial pressure (LAP) and simulate conditions that result in atrial suction. The results showed a time constant characteristic of a compliance lag in LAP response to changes in right pump output in the TAH configuration. These results may prove useful in the design of a new mock circulatory system that incorporates the dynamics of the pulmonary circulation, and in the improvement of existing control algorithms that prevent atrial wall collapse. PMID- 17271118 TI - A closed-loop model of the ovine cardiovascular system. AB - We develop a closed-loop model of the ovine cardiovascular system, with the long term goal of developing a platform for simulating the hemodynamic efficacy of cardiopulmonary assist devices implanted and tested in this animal. The modeling of the systemic circulation is distributed and divided into subsystem circulations. Nonlinear aspects of the systemic venous system are included, such as the pressure-volume relation (PVR) of the systemic veins. In addition, a lumped model of the neural system controlling blood pressure is incorporated. The complete model provides good approximations to measured data from healthy reclining sheep. Moreover, it can predict the hemodynamic changes that accompany pre-load variation upon standing, and the short-term neurally mediated cardiovascular responses that attend this imposed orthostatic stress. We conclude that the model can serve as a simulation platform for evaluating cardiovascular and pulmonary assist devices. PMID- 17271119 TI - Energetics and hemodynamic changes of normal and various right heart bypass (Fontan) circulations in lambs under varying respiration parameters. AB - The Fontan circulation or one of its many modifications is a common surgical procedure implemented in children with congenital heart defects to improve pulmonary circulation. Two modifications are the atriopulmonary connection (AP) and the modified total cavopulmonary connection (TCPC). Successful AP and TCPC operations performed in lambs show respiration has a major influence on systemic and pulmonary hemodynamics. Instantaneous pressure and flow waveforms are obtained before and after the procedure and energies are calculated. Hemodynamic changes in relevant vessels are also acquired. Time delays due to respiration will be calculated and transfer functions computed. The purpose of this study is to examine these waveforms and energy gains/losses under varying respiration parameters in order to aid in determining an optimal surgical protocol as well as assist in the development an accurate computer simulation model. PMID- 17271121 TI - Devices to improve coronary artery bypass grafting (CABG) surgery. AB - As off-pump coronary artery bypass grafting becomes the method of choice for cardio-thoracic surgeons, it has become apparent that the facilitation of coronary artery anastomosis on a beating heart needs to be addressed by improved instrumentation. We propose an intraluminal anastomosis device used in conjunction with a biologic-glue to eliminate suturing and serve as a scaffold for constructing stable anastomoses. The device will continue to serve as an eluting stent postoperatively. The simple technique of using the device and the adhesive will require 5 minutes or less for anastomosis. Moreover, we introduce a novel parallel port vacuum stabilizer foot equipped with a uniform lateral tension inducing turnbuckle mechanism to be used with off-pump stabilization systems. A proposed in vitro protocol details using saphenous vein segments and coronary arteries to test the patency of multiple end-to-side grafts. A pressure transducer will be attached to the graft to monitor flow characteristics. An in vivo protocol details construction of anastomoses during off-pump coronary artery bypass grafting in pigs using the anastomosis device, the turnbuckle vacuum foot, and the biologic-glue. Anastomosis patency will be evaluated intraoperatively and one month postoperatively. Furthermore, the graft site will be examined via flow measurement, angiography, and histological analysis. PMID- 17271120 TI - Flow patterns and wall shear stress distributions at atherosclerotic-prone sites in a human left coronary artery--an exploration using combined methods of CT and computational fluid dynamics. AB - Computed tomography (CT) slices are combined with computational fluid dynamics (CFD) to simulate the flow patterns in a human left coronary artery. The vascular model was reconstructed from CT slices scanned from a healthy volunteer in vivo. The spatial resolution of the slices is 0.6 x 0.6 x 0.625 mm so that geometrical details of the local wall surface of the vessel could be considered in the CFD modeling. This level of resolution is needed to investigate the wall shear stress (WSS) distribution, a factor generally recognized as a related to the atherogenesis. The WSS distributions on the main trunk and bifurcation of the left coronary artery of the model in one cardiac cycle are presented, and the results demonstrate that low and oscillating WSS is correlative with clinical observations of the atherosclerotic-prone sites in the left coronary artery. PMID- 17271122 TI - A system for on-line laser Doppler monitoring of ECG-traced myocardial perfusion. AB - Laser Doppler perfusion monitoring (LDPM) is an established method for microvascular measurements. When applied to the beating heart, however, movement artifact contributions will result in an overestimation of the perfusion. In order to overcome this problem, the perfusion signal may be processed in relation to intervals in the cardiac cycle with minimal tissue motion, e.g., in late systole and late diastole. The aim of this study was to develop an electrocardiogram (ECG) tracing algorithm for R, T and P wave detection and to use these peaks to process the perfusion in intervals with minimal motion. The algorithm, evaluated in three subjects, detected the peaks correctly to 99.9% under ideal conditions. Used on a heart patient in postoperative care this was reduced to 93.2%. However, since the overall goal is to monitor changes in the myocardial perfusion over hours or even days, it is not necessary to capture perfusion values in every single heartbeat. Time traces of perfusion captured in relation to the T and P waves showed a periodical behavior. In order to tune the processing and presentation of the perfusion signal, future studies will focus on long term monitoring of myocardial perfusion during heart surgery and in the postoperative care. PMID- 17271123 TI - Blood flow in stented coronary artery: numerical fluid dynamics analysis. AB - Recent generalization of stent implantation in interventional cardiology require full understanding of blood flow cartography. Interdepency between fluid stresses and in vivo cells covering lumen artery are regularly accused to be one of the instigator of neointimal proliferation (thickening of the inner layer of blood vessels) and mid-term restenosis. This study purpose to numericaly investigate the three dimensional flow in vicinity of an endoprothesis. We used a finite element method to simulate a steady flow of non-Newtonian fluid in a coronary artery using a rigid wall approximation. Results on the velocities, wall shear stress and wall shear stress gradients are presented. Theses simulations allow identification of stagnation site and low wall shear stress area that may be prone to clot formation and neointimal hyperplasia. Intra stent flow knowledge can potentially contribute to optimization of prothesis design and decreasing second intervention rate. PMID- 17271124 TI - Identification of brachial artery characteristic using a cuff for noninvasive detection of coronary artery disease. AB - How could a cuff cause a peripheral artery to enter its resonance mode? How could the arterial oscillations be used to evaluate the arteries and to diagnose coronary artery disease (CAD)? This paper answers. A conceptual model representing the role of cuff-artery connection to produce a step-like (sharpened) pressure stimulator is also introduced. The arterial dynamic response is recorded noninvasively in the form of arterio- oscillo-gram (AOG) via an accelerometer. Only, the big oscillatory parts of AOG are used to assess the arterial structure. Due to CAD correlation with peripheral arteriosclerosis, the CAD can also be diagnosed by analyzing AOG peaks. For every person of 51 samples including 22 CAD, 22 normal and 7 heart murmur (HM) patients, the mean of five largest peak durations is calculated. The more severity of CAD causes the less duration time. Hence, simply, by defining a threshold of 9.25 ms, two CAD and non CAD groups were classified with accuracies of 77% (17/22), and 82% (17/22 for normal, and 7/7 for HM), respectively. This simple noninvasive method mainly aims the vascular characteristics evaluation, thus it does not have the usual limitations of other CAD detection methods. PMID- 17271125 TI - A computational model of microcirculatory network structure and transient coronary microcirculation. AB - Detailed existing studies on microvessels are combined within a biophysically based modeling framework to construct a mathematical and computational model of the coronary microcirculation. Morphometric data of porcine coronary arteries, veins and capillaries are used to build a network structure of a capillary bed. The Poiseuille flow steady state equations are solved on the capillary model and coupled to a transient, finite difference flow model applied to the arteriole/venule networks. The coupling of the two schemes is achieved using a non-linear root-finding algorithm which seeks to satisfy the flow and pressure conditions at the interfacing vessels simultaneously. Convergence is achieved rapidly in a small-scale network. Empirical models of phase separation and Fahraeus-Lindqvist effect are incorporated to account for the non-Newtonian properties of blood in microvessels. Apparent blood viscosity is modeled as a function of vessel diameter and hematocrit (volume fraction taken up by red blood cells) and their solution is iterated at each time step of the finite difference scheme. The resulting algorithm is able to assess the transient flow occurring in a spatially-heterogeneous network while maintaining its computational efficiency and the biophysical basis. PMID- 17271126 TI - Analysis of normal swallowing sounds using nonlinear dynamic metric tools. AB - Several metric tools for quantative analysis of scalar time series have been developed using the theory of nonlinear dynamics. The goal of this work was to study the characteristics of swallowing sound using these metric tools. Takens method of delays was used to reconstruct multidimensional state space representation of the swallowing sounds of 6 healthy subjects (ages 13-30 years, 3 males) being fed thin and thick liquid textures. The optimum time delay for different subjects varied from 3 to 9 samples. False nearest neighbors method was used to obtain proper embedding dimension. The correlation dimension was calculated based on Grassberger-Procaccia algorithm. The results suggest that swallowing sound is well characterized by a small number of dimensions. The largest Lyapunov exponent was also estimated to evaluate the presence of chaos. As the largest Lyapunov exponent for some cases was negative, it may be concluded that swallowing sound is not necessarily a chaotic process. PMID- 17271127 TI - Automated classification of swallowing and breadth sounds. AB - The goal of this study was to develop an automated and objective method to separate swallowing sounds from breath sounds. Swallowing sound detection can be utilized as part of a system for swallowing mechanism assessment and diagnosis of swallowing dysfunction (dysphagia) by acoustical means. In this study, an algorithm based on multilayer feed forward neural networks is proposed for decomposition of tracheal sound into swallowing and respiratory segments. Among many features examined, root-mean-square of the signal, the average power of the signal over 150-450 Hz and waveform fractal dimension were selected features applied to the neural network as inputs. Findings from previous studies about temporal and durational patterns of swallowing and respiration were used in a smart algorithm for further identification of the swallow and breath segments. The proposed method was applied to 18 tracheal sound recordings of 7 healthy subjects (ages 13-30 years, 4 males). The results were validated manually by visual inspection using airflow measurement and spectrogram of the sounds and auditory means. The algorithm was able to detect 91.7% of swallows correctly. The average of missed swallows and average of false detection were 8.3% and 9.5%, respectively. With additional preprocessing and post processing, the proposed method may be used for automated extraction of swallowing sounds from breath sounds in healthy and dysphagic individuals. PMID- 17271128 TI - Swallowing sound characteristics in healthy and dysphagic individuals. AB - This paper proposes a non-invasive, acoustic-based method to differentiate between individuals with and without dysphagia or swallowing dysfunction. Swallowing sound signals, both normal and abnormal (i.e., at risk of some degree of dysphagia) were recorded with an accelerometer over the trachea. Segmentation based on waveform dimension trajectory (WDT, a distance-based technique) was developed to segment the non-stationary swallowing sound signals. Two characteristic sections emerged, Opening and Transmission, and 24 characteristic features were extracted and subsequently reduced via discriminant analysis. A discriminant algorithm was also employed for classification, with the system trained and tested using the leave-one-out approach. Overall, 350 signals were used from three bolus consistencies (semisolid, thick and thin liquids). A final screening algorithm correctly classified 13 of 15 control subjects and 11 of 11 subjects with some degree of dysphagia and/or neurological impairments. The proposed method has great potential to reduce the need for videofluoroscopic swallowing studies (the current gold standard method for swallowing assessment, which is invasive and non-portable) and the overall clinical assessment of swallowing sound signals. PMID- 17271129 TI - Adaptive modeling of sound transmission in the respiratory system. AB - In this study, adaptive filtering techniques have been used in an attempt to model the respiratory system. The respiratory system has been considered as a dynamic system for which input-output relationship is to be defined. Simultaneous measurement of the respiratory sounds over the trachea and posterior chest were made, with the signal from the trachea forming the input to a finite impulse response filter and the signal from the posterior chest forming the desired response of the filter. The chest cavity was stimulated with speech sounds. Least mean square algorithm was used to update filter coefficients. The learning curves of the filter are presented in the paper. It can be concluded that adaptive filtering is a promising way to characterize transmission characteristics of the respiratory system and further improvement may be obtained if anatomical information is integrated in the modeling process. PMID- 17271130 TI - A comparison of various respiratory system models based on parameter estimates from impulse oscillometry data. AB - Impulse oscillometry offers an advantage over spirometry when conducting pulmonary function tests. Not only does it require minimal patient cooperation, it provides useful data in a form amenable to engineering methods. In particular, the data can be used to obtain parameter estimates for electric circuit-based models of the respiratory system, which can in turn aid the detection and diagnosis of various diseases/pathologies. Of the six models analyzed during this study, the DuBois model and a newly proposed extended RIC model seem to provide the most robust parameter estimates for our entire data set of 106 subjects with various respiratory ailments such as asthma and chronic obstructive pulmonary disease. Such a diagnostic approach, relying on estimated parameter values, may require additional measures to ensure proper identification of diseases/pathologies but the preliminary results are promising. PMID- 17271131 TI - On applying continuous wavelet transform in wheeze analysis. AB - The identification of continuous abnormal lung sounds, like wheezes, in the total breathing cycle is of great importance in the diagnosis of obstructive airways pathologies. To this vein, the current work introduces an efficient method for the detection of wheezes, based on the time-scale representation of breath sound recordings. The employed Continuous Wavelet Transform is proven to be a valuable tool at this direction, when combined with scale-dependent thresholding. Analysis of lung sound recordings from 'wheezing' patients shows promising performance in the detection and extraction of wheezes from the background noise and reveals its potentiality for data-volume reduction in long-term wheezing screening, such as in sleep-laboratories. PMID- 17271132 TI - Analysis of wheezes in asthmatic patients during spontaneous respiration. AB - Respiratory sound analysis can offer important information related to pulmonary diseases. Wheezes have been reported as adventitious respiratory sounds in asthmatic or obstructive patients, during forced exhalation maneuvers. In this work, we propose a method for analysis of respiratory sounds in frequency domain, during spontaneous ventilation. Two databases were analyzed: signals acquired during spirometry (DBspir), composed by 23 subjects (N=15 asthmatics, N=8 control); and signals acquired during spontaneous ventilation for 120 seconds (DBsv), composed by 26 asthmatics. Using an autoregressive model (AR, order 16), it was calculated the Power Spectral Density (PSD) for each expiration and the peak frequency (fp) was estimated. Higher values of fp were found in asthmatic patients with severe obstruction in relation to light obstruction or control subjects. The effect of bronchodilator inhalation in asthmatic patients was studied in the database DBsv, analyzing contribution of wheezes in the bandwidth 600-2000 Hz (HFband)., Differences of number of respiratory cycles with wheezes (Dwheez index), before and after bronchodilator inhalation were evaluated. It was found a good correlation between Dwheez and FEV1% improvement (FEV1>%_imp), for FEV1%_imp > 10%. This method could predict the FEV1%_imp by means of estimation of Dwheez index during spontaneous ventilation. PMID- 17271133 TI - Heart sound cancellation based on multiscale products and linear prediction. AB - This paper presents a novel method for Heart Sound (HS) cancellation from Lung Sound (LS) records. The method uses the multiscale product of the wavelet coefficients of the original signal to detect HS segments. Once the HS segments are identified, the method removes them from the wavelet coefficients at every level and estimate the created gaps by either an autoregressive or moving average model. It is shown that if the segment to be predicted is stationary, a final record with no audible artifacts such as clicks can be reconstructed using this approach. The results were promising for HS removal from LS without hampering the main components of the LS. The results were confirmed both qualitatively by listening to the reconstructed signal and quantitatively by spectral analysis. PMID- 17271134 TI - Classification of lung sounds during bronchial provocation using waveform fractal dimensions. AB - Lung sounds (LS) of children after bronchoconstriction should differ from baseline LS in terms of amplitude and pattern characteristics. To test these hypotheses, time-domain and fractal based analyses have been applied to LS acquired from eight children ages 9-15 y pre- and post-methacholine challenge (MCh). Change in forced expiratory volume in 1 s after MCh ranged from -4% to 37%, with change proportional to severity of bronchoconstriction. Sounds were recorded over the posterior right lower lung lobe while subjects breathed normally for 60 s with flow measurement, and during 10 s of breath hold (BH). From root-mean-square (RMS) of LS and BH signals, signal-to-noise ratio (SNR) was determined. Two fractal dimension (FD) algorithms were applied, based on signal variance and morphology. Feature vectors for 1-nearest-neighbor classification contained FD and RMS values within flow plateau ranges. Results for LS within 75 600 Hz indicate that the combination of RMS-SNR and morphology-based FD values offers better classification of bronchoconstriction with LS, relative to using RMS-SNR with variance-based FDs and RMS-SNR alone. True positive classification was 90.3%, 63.5% and 58.3% respectively, and false positive classification was 23.4%, 24.9% and 26.1% respectively. Both RMS-SNR and FD values provide useful insight into LS changes post-bronchoconstriction. PMID- 17271135 TI - Classification of pulmonary diseases based on impulse oscillometric measurements of lung function using neural networks. AB - Central and peripheral airflow obstructions frequently occur in patients with chronic obstructive lung disease or asthma and may have different pathophysiological mechanisms of obstruction and require different therapeutic interventions. Impulse oscillometry (IOS) is a patient-friendly method for studying respiratory function in health and disease. The enormous variety of patterns and the high degree of variability in the measured lung function parameters has made the automated diagnosis of pulmonary diseases very desirable by pulmonary physiologists and clinicians. Computer aided diagnosis can serve as a second but quantitative opinion to diagnosis and screening. Presently, there are no robust algorithms to classify the IOS patterns into particular disease groups. In this work, an artificial neural network (ANN) was used to recognize and classify the disease of the central and peripheral airways. Using IOS measurements in 131 patients, a training set was created and used in a feedforward ANN that was trained by backpropagation algorithm to classify pulmonary diseases as either central or peripheral. After supervised training, the ANN was presented with the same data and produced a 98.47% correct classification rate. When a new set of unseen data was used, the classification accuracy was reduced to 61.47%. Having produced a promising classification rate in the first case, the accuracy of this classifier could be further improved. Inclusion of more training samples combined with fuzzy logic decision rules could facilitate the development of a software tool that assists pulmonary specialists with their diagnosis of lung function using the patient-friendly IOS system. PMID- 17271136 TI - Finding the lung sound-flow relationship in normal and asthmatic subjects. AB - To investigate the relationship between lung sound (LS) and flow, we studied LS signals from 5 healthy adults (group I), 10 healthy children (group II) and 7 asthmatic children (group III). The LS signals were recorded on right upper lung lobe at different flow rates varied from 0.4 to 3.0 L/s and the flow signals were measured at mouth. The LS and flow signals were parsed into segments of 1024 data points with 50% overlap between successive segments. The mean LS amplitude (mean AMP) and mean flow (flow) were calculated for each segment. The average power (Pave) of each segment was calculated from LS spectrum for different frequency bands between 20-600 Hz. Four different types of models, representing the relationship between mean AMP or Pave and flow, were investigated using different percentage of flow signal in each inspiratory phase. The model coefficients were derived from either linear regression analysis or polynomial curve fitting between the data and model variables. The correlation coefficients (r) between the experimental data and data estimated from the model coefficients were calculated for each subject in each model and averaged between the subjects. The results showed much stronger correlation between Pave and flow than mean AMP and flow for all groups. The best model to describe Pave relationship with flow was found to be power relationship in both healthy adults and children whereas a third-order polynomial curve best fitted the Pave and flow data in asthmatic group. The optimum frequency band to calculate Pave was found to be 150-450 Hz for healthy subjects and 300-600 Hz for asthmatic children. The diminution of heart sound (HS) from LS recordings showed no change in the selected model in all three groups. The results of this study suggest the difference in Pave- flow relationship in healthy and asthmatic subjects may be used as a diagnostic tool for asthma. PMID- 17271137 TI - Ambulatory recording of sleep apnea using peripheral arterial tonometry. AB - Sleep related breathing disorders are common. A reliable diagnosis with relatively simple and portable methods is still needed. One approach is to make use of autonomous nervous system changes which accompany disordered breathing during sleep. The peripheral arterial tonometry (PAT) determines the peripheral arterial vascular tone using a plethysmographic method on the finger. The peripheral arterial tone is modulated by sympathetic activity, by peripheral blood pressure, and by the peripheral resistance of the vessels. We investigate a new ambulatory recording device which uses PAT, oximetry and actigraphy in order to detect sleep apnea. For this purpose we performed a comparative study on 21 patients referred to our sleep laboratory due to suspected sleep apnea. Of these 17 valid recordings were compared. The Watch-PAT was used in parallel with cardiorespiratory polysomnography and the validity was determined. The new system is able to detect apneas and hypopneas with a high reliability (r=0.89). It is very sensitive to arousals (r=0.77). Since arousal are not specific to sleep apnea the specificity of the new system could not be finally clarified in this study. We conclude that the new system is very well suited to perform control studies in patients with sleep apnea which are under therapy and require regular follow-up investigations to maintain a high CPAP compliance. PMID- 17271138 TI - The use of esophageal manometry in the diagnosis of sleep-related breathing disorders. AB - Esophageal manometry is a technique used to detect abnormal sleep-related respiratory events. One method used to measure and score esophageal pressure during sleep is described. The contraindications for esophageal manometry, the methods for scoring esophageal pressure, the use of esophageal manometry as the "gold standard", and directions for future research are discussed. PMID- 17271139 TI - Central aortic pressure wave changes with sleep stage and disordered breathing in children estimated by application of an arterial transfer function to peripheral blood pressure. AB - We have developed an arterial transfer function using aortic and peripheral blood pressure waves measured simultaneously in healthy children undergoing diagnostic catheterization. We have applied this transfer function to peripheral blood pressure pulses measured during specific stages of sleep and at distinct points in the respiratory cycle in a different set of children with and without sleep disordered breathing to estimate the central aortic pressure wave shape. PMID- 17271140 TI - Non-invasive estimation of esophageal pressure based on intercostal EMG monitoring. AB - Recording of esophageal pressure waveform is an important clinical tool to identify patients with sleep-disordered breathing. Commonly, esophageal pressure probes are not tolerated by patients undergoing sleep monitoring. We therefore developed a technique to non-invasively estimate esophageal pressure based on recording of intercostal EMG monitoring. A three step approach to modification of the intercostal EMG signal was created to closely match results obtained from esophageal pressure recording. The algorithm was then tested on 10 subjects with sleep-disordered breathing undergoing full polysomnography with simultaneous monitoring of esophageal pressure and intercostal EMG. Analysis of correlations between esophageal pressure and intercostal EMG were computed by sleep stages. The overall correlation coefficient in all subjects combined was r=0.896, p<0.00001. The results indicate that this method can be used reliably in clinical sleep studies where esophageal pressure recordings cannot be performed. PMID- 17271141 TI - Noninvasive assessment of cardiovascular autonomic control in congenital central hypoventilation syndrome. AB - The goal of this study was to quantify autonomic system dysfunction, as manifested by cardiovascular and respiratory response abnormalities, in patients with congenital central hypoventilation syndrome (CCHS). During wakefulness, we continuously measured the ECG, arterial blood pressure (ABP), airflow, end-tidal CO2 partial pressure (PETCO2), and arterial oxygen saturation (SatO2) in each subject. These measurements were made during spontaneous breathing in supine, sitting and standing postures, and also when each subject tracked his/her prior spontaneous breathing pattern while supine. We also performed the cold face test, hyperoxic hypercapnic rebreathing and the isocapnic hypoxic rebreathing challenges. Using spectral analysis and modeling techniques, we sought to computationally delineate the physiological mechanisms that mediate these abnormalities, as well as to determine the extent to which these abnormalities are related to peripheral or central chemoreflex dysfunction. Our preliminary results support the notion that sympathetic tone is markedly elevated in CCHS, and that differences in autonomic control from normal controls can be delineated by observing the responses to different stressors. PMID- 17271142 TI - Long-term monitoring of sleep apnea at home in heart failure patients: preliminary results from the HHH study. AB - Sleep apnea is very common in patients with chronic heart failure (CHF) and has important implications in terms of morbidity, mortality and clinical management. Home respiratory telemonitoring might constitute a potential low-cost, widely applicable alternative to traditional polysomnography in the evaluation and long term monitoring of breathing disorders in these patients. In this paper we briefly describe the technological infrastructure and present preliminary results of the European Community multicountry trial HHH (Home or Hospital in Heart Failure), which is currently testing a novel system for home telemonitoring of cardiorespiratory signals in CHF patients. The recording and transmitting devices are suitable to be self-managed by the patient. We give a detailed report on the prevalence of nocturnal respiratory disorders at the beginning of the one-year follow-up and on their persistency over the following recordings (one per month). These preliminary findings clearly indicate that intermittent home telemonitoring of respiratory signals based on patient's self-management is feasible in CHF patients and the compliance is high. Reported statistics unambiguously confirm the high prevalence of nocturnal breathing disorders in these patients and clearly show that this phenomenon tends to persist over time. PMID- 17271143 TI - Women have a greater ventilatory responses to upper airway obstruction than men. AB - We examined whether gender specific differences exist in defending inspiratory tidal volumes in the face of upper airway obstruction. In normal weight- and aged matched men (n=9) and women (n=9), we induced upper airway obstruction with inspiratory flow limitation during NREM sleep by exposing individuals to sub atmospheric nasal pressure. The mean inspiratory airflow was used to define three distinct levels of upper airway obstruction, based on a mean inspiratory airflow of 175-225 ml/s, 125-175 ml/s and 75-125 ml/s. While duty cycle responses were similar between genders, women had a greater response in T(TOT) at all flow limited conditions. (p<0.05). However, the greater response in T(TOT) led to a more pronounced decline in tidal volume in women compared to men (p<0.05), particularly during the mild and moderate upper airway obstruction. Our data demonstrate that the respiratory rate determines the tidal volume during periods of upper airway obstruction and indicate that individuals with a higher respiratory rate are at risk to develop hypoventilation in face of upper airway obstruction. Because women have a more brisk response in the respiratory rate than men, this may explain the difference in the expression of sleep disordered breathing between genders. PMID- 17271144 TI - The use of R-wave morphology in the detection of sleep-disordered breathing using the electrocardiogram--a comparison between leads. AB - Power spectral analysis of time series derived from the R-wave morphology of the ECG was employed to identify a suitable lead configuration for the detection of sleep-disordered breathing (SDB) using the electrocardiogram (ECG). 16 subjects (46 +/- 9.2 yrs, 8 males), who did not report problems during sleep, and 13 subjects previously diagnosed with SDB (49 +/- 8.8 yrs, 7 males) underwent an overnight sleep study at an accredited sleep center. Power values derived from the spectra of the R-peaks envelope were tested for their sensitivity and specificity in discriminating between epochs containing normal breathing from epochs containing SDB. Of the three tested lead configurations using two parameters NB1 and NB2 derived from the power spectrum, lead I produced the best results with a sensitivity of 92.8% and a specificity of 88.0% for the case of parameter NB1 and a sensitivity of 85.7% and a specificity of 76.0% for the case of parameter NB2. PMID- 17271145 TI - Time domain analysis of R-wave attenuation envelope for sleep apnea detection. AB - Time domain analysis was carried out on the R-wave attenuation (RWA) envelope of the subjects with and without obstructive sleep apnea. The RWA envelope is derived from the morphology of the electrocardiogram (ECG) obtained during polysomnography data collection of the subjects. Nocturnal polysomnography was performed on 16 normal subjects and 14 obstructive sleep apnea (OSA) patients. The ECG from the polysomnography data was divided into fifteen minute epochs for analysis. The QRS detection was carried out by an algorithm using Hilbert transform. Standard deviation of each of the fifteen one minute epochs in fifteen minute epoch of the RWA envelope was calculated. Standard deviation of these fifteen parameters was observed to have considerably good sensitivity and specificity to sleep apnea. For the clips selected from normal subjects, the parameter produced a sensitivity of 78.57% and specificity of 70.33% for the training set and sensitivity of 87.5% and specificity of 80.95 for the testing set. For the clips selected from OSA subjects, the parameter produced a sensitivity of 72.46% and specificity of 73.53% for the training set and sensitivity of 82.86% and specificity of 66.67% for the testing set. PMID- 17271146 TI - Heart rate chaos in obstructive sleep apnea in children. AB - Obstructive sleep apnea syndrome (OSAS) in children is associated with a bradytachyarrhythmia during an obstructive event. Polysomnographic recordings were obtained from 15 children; 9 had OSAS (apnea/hypopnea index = 13.6 +/- 8.2/hr, mean +/- SD) and 6 normal controls. Heart rate variability was analyzed for the presence of chaotic dynamics. Using a 5-minute sliding window, chaos was detected using numerical titration technique. In both groups, REM had a higher chaotic intensity than NREM sleep (p < 0.05). Furthermore, chaos was significantly increased during periods with apneic events compared to stable breathing. These data indicate that sleep state and disordered breathing are important determinants of the autonomic control of heart rate chaos in children. PMID- 17271147 TI - Closed-loop minimal model analysis of the cardiovascular response to transient arousal from sleep in healthy humans. AB - In a previous work we reported discrepancies in the cardiovascular response to arousal from NREM sleep between OSAS patients and healthy controls. The long lasting cardiac sympathetic increase observed in normals was not present in the OSAS group, whereas the peripheral vasculature reaction was similar between the two groups. Analysis of REM arousal revealed that there was a similar temporary cardiac sympathetic impairment in the control group. In this work we have implemented a model-based time domain system identification method to assess the mechanisms involved in this reaction to arousal from both NREM and REM sleep in a group of healthy subjects. The use of time-varying techniques has enabled us to characterize the arousal reaction by analyzing the change in shape of the impulse responses of the system. The mechanisms regulating respiration and vascular effects on heart rate (respiratory sinus arrhythmia or RSA and arterial baroreflex or ABR, respectively) were the most affected by NREM arousal, likely as a result of the return of the wakefulness stimulus. The effect observed on the cardiac influence on the vasculature (circulatory dynamics, CID) was attributed to a change in the dominant mechanism prevailing in its dynamics. PMID- 17271148 TI - The effects of repetitive arousal from sleep on cardiovascular autonomic control. AB - A previous study found that the sympathoexcitatory cardiovascular effects of arousal are relatively long lasting. In this study, we examine (1) whether the cumulative effects of arousal can lead to significant changes in autonomic control and (2) how the frequency of arousals affect the magnitude of these effects. Ten healthy subjects were aroused from sleep every 30 seconds, 1 minute and 2 minutes of sleep for an hour. EEG, ABP, ECG and respiration were recorded, and the impulse responses of respiratory sinus arrhythmia (h(RSA)) and arterial baroreflex (h(RSA)) before and after 50 minutes of repetitive arousal were quantified by using a minimal closed loop cardiovascular model. We found that the low frequency baroreflex gain decreased after exposure to repetitive arousals of 2 minutes periodicity but remained unchanged in the control and other arousal conditions. PMID- 17271149 TI - Simulation of spontaneous cardiovascular variability using PNEUMA. AB - In a previous study, we introduced PNEUMA, a physiologically realistic comprehensive model incorporating the respiratory, cardiovascular and neural control systems, aimed at characterizing cardiorespiratory mechanisms during sleep disordered breathing. The goal of this study was to integrate the pulsatile heart and comprehensive pulmonary and systemic circulation components into the existing PNEUMA model for investigation of the cardiovascular regulation mechanisms leading to heart period fluctuations. All model parameters were given on the basis of actual physiological data from literature. The autoregressive spectral analysis was performed to evaluate model generated RR intervals: the results of spectral analysis of RR intervals suggest that our model correctly accounts for major key aspects of autonomic control that are known to contribute into RR variability. PMID- 17271150 TI - Effects of cardiovascular parameter changes on heart rate variability: analysis by a mathematical model of short-term cardiovascular regulation. AB - A mathematical model of short-term cardiovascular regulation is used to investigate how heart period power spectrum reflects alterations in cardiovascular parameters. The model includes the pulsating heart, the systemic and pulmonary circulation, the mechanical effects of respiration on hemodynamics, two groups of receptors (arterial baroreceptors and lung-stretch receptors), the sympathetic and vagal efferent branches, several distinct effectors, and a very low frequency vasomotor noise. All parameters in the model are assigned on the basis of the physiological literature. With basal parameter values, the simulated heart period (HP) power spectrum exhibits a high frequency (HF) peak, synchronous with respiration (0.2 Hz) and a smaller low frequency (LF) component around 0.1 Hz. Model results stress that the features of the HP spectrum are influenced by several factors, other than strength and integrity of autonomic nervous system. In particular, sensitivity analyses reveal that alterations in total peripheral resistance and in left ventricle contractility affect HP spectrum markedly, by causing a change in the working point of the autonomic control mechanisms. The model may be useful in the physiopathological interpretation of heart rate variability, to relate changes in HP spectrum with autonomic and/or cardiovascular perturbations. PMID- 17271151 TI - Study of the respiratory pattern variability in patients during weaning trials. AB - Mechanical ventilators are used to provide life support in patients with respiratory failure. One of the challenges in intensive care is the process of weaning from mechanical ventilation. We studied the differences in respiratory pattern variability between patients capable of maintaining spontaneous breathing during weaning trials and patients that fail to maintain spontaneous breathing. The respiratory pattern was characterized by the following time series: inspiratory time (T(I)), expiratory time (T(E)), breath duration (T(Tot)), tidal volume (V(T)), fractional inspiratory time (T(I)/T(Tot)), mean inspiratory flow (V(T)/T(I)), respiratory frequency (f), and rapid shallow breathing index (f/V(T)). The variational activity of breathing was partitioned into autoregressive, periodic and white noise fractions. Patients with unsuccessful trial presented a tendency to higher values of gross variability of V(T)/T(I) and f/V(T), and lower values of T(I). The autocorrelation coefficients tended to present higher values for T(I), T(I)/T(Tot) and V(T)/T(I). During both successful and unsuccessful T-tube test uncorrelated random behavior constituted > 75% of the variance of each time breath components and represented 50 to 70% in the breath component related to V(T). Correlated behavior represented 6 to 21% in time components and 28 to 50% in component related to V(T). PMID- 17271152 TI - Modeling and evaluation of respiratory and muscle pattern during hypercapnic stimulus. AB - Understanding the respiratory control system and the ventilatory pattern under hypercapnic stimulus is important to interpret the acute exacerbation of COPD and the condition of patients connected to mechanical ventilation. The purpose of this study is the analysis of respiratory and muscle parameters in order to obtain the most sensitive and characteristic of different levels of hypercapnic stimulus. Parameters defined and calculated from pressure signals show the highest variations with the increment of stimulus. Other ones like exhaled ventilation or ratios between respiratory parameters are more influenced by hypercapnia than tidal volume, respiratory frequency or even end tidal CO2. Muscle parameters from electromyographic signals of three respiratory muscles are calculated in time and frequency domain. In spite of greater variability between subjects, the most interesting muscles because of their activation with higher stimulus are in the following order: diaphragm, sternomastoid and genioglossus. Moreover, a model of respiratory control system is evaluated in order to predict and simulate appropriately this ventilatory stimulus. In spite of scattered real data, they are compared with simulation results obtained by the model and predicted by means of a specific respiratory optimization. PMID- 17271153 TI - Assessment of respiratory muscle effort studying diaphragm movement registered with surface sensors. Animal model (dogs). AB - The diaphragm movement (DM) signal during spontaneous ventilations is analyzed in this work. The DM signal is acquired by means two surface sensors (a piezoelectric contact sensor -PCS- and a piezoelectric accelerometer -ACP) applied on the costal wall. The main objective is to develop a new non invasive technique to assess respiratory muscle effort. Experiments were performed in an animal model: four pentobarbital-anesthetized and two awake mongrel dogs, carrying out spontaneous ventilations against an inspiratory load. DM signal has been decomposed in two components: a low frequency component (lower than 5 Hz) due to the overall lateral movement of the muscle (MOV component), and a high frequency component (higher than 5 Hz) due to the lateral vibration of active muscle fibers (VIB component). It has been seen that the PCS acquires only MOV components of MD signal, while ACP acquires both components. Positive high correlation coefficients have been found between amplitude parameters of VIB components of DM signal, acquired by means the ACP, and the respiratory muscle effort during ventilation, measured with inspiratory pressures. PMID- 17271154 TI - Detection of expiratory flow limitation during mechanical ventilation: a simulation study. AB - Expiratory flow limitation (EFL) is frequent in mechanically ventilated patients with obstructive pulmonary disease and its prompt detection is important to optimize respiratory assistance. The present study aims to compare by simulation two methods for the detection of flow limitation in intensive care unit: the negative expiratory pressure (NEP) method and the external resistance (DeltaR) method. To this purpose, a non linear dynamic morphometric model of breathing mechanics, derived from the Weibel symmetrical description of lungs, was used to simulate a normal and an obstructive respiratory condition during artificial ventilation. Both methods revealed the presence of EFL in the pathological case. The NEP method seems to promote the collapse of the upper and intermediate airways, so producing an overestimation of the pathology result. On the contrary, during the DeltaR maneuver the same airways increase their radius and, therefore, EFL appears underestimated. The DeltaR method appears less practical with respect to the NEP method, because of the procedure required to select the appropriate resistance degree. Moreover the flow limited portion of expiration estimated by the DeltaR technique sounds rather dependent on the choice of the external resistance level. PMID- 17271155 TI - Modeled velocity of airflow in the airways during various respiratory patterns. AB - Our modeling and simulation of the respiratory system with Weibel's morphometry shows that the average velocity of expiratory airflow is always greater than the average velocity of inspiratory airflow during tidal breathing when the intervals of inspiration and expiration are same. A nonlinear circuit model was developed comprised with the upper airway, the conducting airways (trachea approximately terminal bronchioles), and the lumped alveolar space. These compartments are established with known physiologic pulmonary characteristics that are represented by nonlinear resistors and capacitors. In this paper we set up the circuit model reflecting the geometric variation of airways during tidal breathing, and demonstrated computation results for the velocity of airflow along the airways based on 16 different respiratory patterns. The circuit model offers a convenient method that can be used to investigate the velocity of airflow and its interaction with mucus, as well as suggests a basic model for our future research on analyzing airway clearance techniques. PMID- 17271156 TI - Hybrid algorithm for automatic regulation of mechanical ventilation in premature infants based on expert rules and proportional differential control. AB - Mechanically ventilated premature infants present with fluctuations in ventilation that cannot be addressed by conventional mechanical ventilation with fixed positive pressure and constant frequency. A hybrid algorithm for automatic targeting of minute ventilation and tidal volume by individual or combined closed loop control of the ventilator frequency and peak inspiratory pressure was developed. The objective of this system is to minimize the mechanical support and adapt to changes in ventilatory need. Under the most challenging conditions, the combined controller is more efficient than individual control. PMID- 17271157 TI - Air-flow simulation in realistic models of the trachea. AB - In this article we present preliminary results from a new technique for flow simulation in realistic anatomical airways. The airways are extracted by means of Level-Sets methods that accurately model the complex and varying surfaces of anatomical objects. The surfaces obtained are defined at the sub-pixel level where they intersect the Cartesian grid of the image domain. It is therefore straightforward to construct embedded boundary representations of these objects on the same grid, for which recent work has enabled discretization of the Navier Stokes equations for incompressible fluids. While most classical techniques require construction of a structured mesh that approximates the surface in order to extrapolate a 3D finite-element griding of the whole volume, our method directly simulates the air-flow inside the extracted surface without losing any complicated details and without building additional grids. PMID- 17271158 TI - An efficient algorithm for R-R intervals series filtering. AB - Spectral analysis of heart rate variability (HRV) constitute a simple and non invasive way to study the autonomic nervous system (ANS) activity. On-line implementation of this technique would allow to follow the evolution of the ANS activity and to track transient events during medical procedures. However, continuous spectral analysis of HRV is not reliable enough due to the difficulty to obtain a noiseless ECG signal during a long period. Indeed, the consequential effects of each ECG signal perturbation on the R-R intervals gives an erroneous evaluation of HRV spectral analysis. In this article, we describe a real time filtering algorithm for R-R intervals series. This filter is able to detect each disturbed area and to replace the erroneous samples with the most probable ones. Therefore, this method allows detecting and replacing up to 90 % of R-R series erroneous samples while keeping the real recording time and without having any effect, beyond measure, on the frequency analysis result. PMID- 17271159 TI - A point process adaptive filter for time-variant analysis of heart rate variability. AB - Estimating time-variant heart variability indices from R-R interval beat series has been widely investigated by current research involving cardiovascular control. Most of the currently accepted approaches in time-variant heart rate analysis ignore the underlying discrete structure of human heart beats, and usually require minutes of data. We derive an adaptive point process Bayes' filter based on a statistical model which considers the stochastic structure of heart beat intervals as a point process. From the explicit inverse Gaussian probability density describing heart rate and heart rate variability we are able to extract and recursively update, at any time resolution, a set of indices related to the first and second moments of this probability density. We apply our algorithm in an analysis of human heart beat intervals from a tilt-table experiment. Our results describe real instantaneous estimates of heart rate variability and may have important implications for research studies of cardiovascular and autonomic regulation. Our algorithm is easy to implement for on-line analysis of heart rate variability in the intensive care unit, operating room or labor and delivery suits. PMID- 17271160 TI - Quantifying cardiac parasympathetic and sympathetic function based on a weighted principal component regression method. AB - A quantitative evaluation of autonomic cardiovascular control is important in understanding basic pathophysiological mechanisms or for patient monitoring, treatment design and follow-up. Noninvasive techniques for this purpose have been the focus of many research endeavors. We previously proposed a method to extract pure parasympathetic and pure sympathetic indices based on the impulse response between instantaneous lung volume and heart rate. Identification of this impulse response involves a dual-input, single-output system in which one input interacts with the output in closed-loop. To identify this relatively complicated system, we propose here a new system identification technique based on a weighted principal component regression method. Asymptotically, this technique implements model selection in the frequency domain. Therefore, in contrast to the conventional methods, it allows the data to play a significant role in determining candidate models. Moreover, the estimated model parameters reflect a trade-off between bias and variance to reach a relatively small mean squared prediction error. We employ experimental data to demonstrate that this technique is superior to a more traditional technique in terms of measuring cardiac autonomic indices. PMID- 17271161 TI - Heart rate and blood pressure variability in patients implanted with rate responsive pacemaker. AB - Rate-responsive pacemakers (PMs) aim at having pacing rates as similar to physiological cardiac rhythms as possible. The pacemaker INOS(2+)-CLS (Biotronik, Germany) implements a closed loop strategy (CLS) based on indirect measures of right ventricle contractility using intracardiac impedance signal. The contractility is, in turn, related to the autonomic nervous system control to the heart. Aim of this study was to evaluate the 24h beat-to-beat heart rate and blood pressure profiles in patients implanted with CLS rate adaptive PM. 24h ECG and arterial pressure waveform acquisition were performed by a digital Holter system by the Portapres equipment, respectively. A proper-designed algorithm was developed to classify PM pacing modalities. For each beat we estimated the heart rate (HR), and the systolic and diastolic pressure values (SP, DP). So far, 6 patients have been studied: 4 patients have been analyzed both with and without rate responsive modalities (DDD-R and DDD, respectively); 2 patients have been studied only with rate-responsive modality. Results obtained in 6 patients show that this rate adaptive PM accurately preserve the heart rate and blood pressure variability throughout the 24h. In particular, the rate adaptation of PM based on impedance measurements succeeds in maintaining the spontaneous HR, SP and DP on a beat-to-beat basis. PMID- 17271162 TI - Response of fetal heart rate to uterine contractions. AB - The heart rate variability of fetuses under stress from maternal uterine contractions conveys critical information to clinicians and also provides theoretical clues about heart rate regulatory mechanisms. According to the polyvagal theory, the deceleration of fetal heart rate under stress is caused by the withdrawal of vagal tone. Recovery is mediated by its reestablishment. An implication of this mechanism is that the respiratory sinus arrhythmia (RSA) is elevated after the deceleration and subsequent recovery. Findings from our clinical data on fetuses support this theory. The data also indicate that in the instance of a late deceleration the RSA may not be elevated after recovery. PMID- 17271163 TI - Complexity analysis of 24 hours heart rate variability time series. AB - We propose to study the heart rate variability (HRV) time series complexity by computing the Lempel Ziv complexity measure. LZ is sensitive to the rate of pattern recurrences in a time series. Analysis considers 24 h HRV time series of healthy subjects and patients with cardiovascular diseases. Analysis with simulated signals show the LZ measure can vary depending on the adopted coding process. The binary coding, proposed in this work, is sensitive to the different dynamical systems generating the time series, as the ternary coding is sensitive to the presence of stationary states, i.e. a consecutive repetition of the same RR interval value. LZ method reliably differentiates healthy vs. disease group. Further clinical investigations on the LZ complexity and on its relationship to the risk of sudden death, can supply new diagnostic indications. PMID- 17271164 TI - Characterization of the critical cycle length of a left atrial driver which causes right atrial fibrillatory conduction. AB - A stable rhythm of very short cycle length (CL) in the left atrium (LA) can cause fibrillatory conduction, particularly in the right atrium (RA). Fast Fourier transform (FFT) analysis reliably identifies LA to RA conduction path(s) during atrial fibrillation (AF). We tested the hypotheses that FFT analysis of atrial electrograms (AEGs) during AF simulation will reliably identify the critical LA driver CL that causes RA fibrillatory conduction (i.e., the critical conduction breakdown CL) and that a longer critical conduction breakdown CL is found in atria of abnormal (sterile pericarditis) compared to normal dogs. We paced from Bachmann's bundle and the posterior-inferior LA at rapid rates to mimic an LA driver. During pacing, 4 sec of FFT analysis of 203 bipolar AEGs was performed and showed: 1) a single dominant frequency peak at the pacing CL in both atria when the atria followed the pacing in a 1:1 manner; 2) multiple and broad frequency peaks on the RA and parts of the LA at the conduction breakdown CL; and 3) the conduction breakdown CL is longer in pericarditis than normal dogs. FFT analysis allowed reliable detection of the critical CL of an LA driver that induces RA fibrillatory conduction. PMID- 17271165 TI - Finite element computer modeling of transthoracic atrial defibrillation. AB - Placement of external electrodes can significantly affect the success rate of transthoracic atrial defibrillation, but studies have not led to agreement on optimal electrode placements. This study aims to (1) develop an anatomically realistic, finite element model of the human torso for external atrial defibrillation, (2) investigate model parameters of skeletal muscle conductivity and anisotropy and the presence of subcutaneous fat, and (3) investigate clinical defibrillation parameters of electrode size, shape, and location. The model predicts atrial defibrillation threshold (ADFT) energy by requiring a voltage gradient of 5 V/cm over at least 95% of atrial myocardium. The model compares favorably with a clinical study of 301 patients that reported an anterior posterior electrode position required approximately 20% less energy than an anterior-anterior position. Results indicate that a change in electrode size has a different effect for different electrode placements. This study finds that variation in electrode placement by only a few centimeters can change ADFTs by up to 51%. This is the first computer model of transthoracic atrial defibrillation to our knowledge. Our computer model is not limited to a few empirically selected electrode placements as in clinical studies and can test any location, size, and number of electrode placements. PMID- 17271166 TI - Defibrillation current density imaging: comparison of in-vivo and post-mortem measurements in a pig. AB - Current density imaging (CDI) is an MRI technique used to measure electrical current density vectors throughout a volume of tissue. Previous work used CDI to measure current pathways through the heart and chest of a post-mortem pig when current is applied using external flexible defibrillation electrodes with typical anterior-anterior positioning. In these post-mortem studies, current pathways were probably influenced by the anisotropic conductivity of the tissues. This work aims to compare post-mortem ( approximately 15 min. and approximately 1 hour after death) results with new in vivo CDI measurements. These measurements indicate that the macroscopic (i.e. across the whole body) current pathways remain similar before and after death, however, at a smaller scale (i.e. distances of a few cm) current pathways are different, particularly in the heart. This comparison demonstrates the influence on current pathways of rapidly changing electric properties of tissue following death. PMID- 17271167 TI - Programmable arbitrary waveform generator for internal defibrillation research. AB - A programmable arbitrary waveform generator for creation of experimental defibrillation shocks is described. The system is capable of delivering shocks for internal defibrillation via 10 channels at 1000 Volts and 30 Amps. A microcontroller driven system that can receive waveform commands from a laptop was designed to be able to deliver shocks to any combination of electrodes. Waveforms are controllable down to 100 microsecond intervals and each channel is capable of serving as anode or cathode. This system can be used to verify predictions for defibrillation waveform efficacy as predicted by modeling efforts or to test new experimental waveforms tuned to parameters from an individual subject. PMID- 17271168 TI - Small random fiber angle variations as a mechanism for far-field stimulation of cardiac tissue. AB - The mechanism by which an electric field stimulates cardiac tissue far from the stimulating electrode is not known. Current theories rely on the inherent heterogeneity of cardiac tissue as contributing to this phenomenon. This paper explores a possible mechanism for far-field stimulation in relation to fiber curvature. We incorporate a randomized fiber angle geometry into a two dimensional active cardiac tissue model with unequal anisotropy ratios already exhibiting smooth, curving fibers. We simulate cross-field stimulation to initiate reentry in the tissue model, and compare the electric field thresholds at different S1-S2 intervals for tissue with randomized fiber angles and tissue with a smooth fiber geometry. The tissue with random fiber angles has a significantly lower threshold for reentry at certain intervals on the strength interval curve. We conclude that a random fiber geometry may have an effect on the mechanism for far-field stimulation. PMID- 17271169 TI - Asymmetry in dynamics of action potential duration transition between steady states: a simulation study. AB - Ventricular fibrillation (VF) contributes importantly to sudden cardiac death, however, exact mechanisms of VF remain elusive. Action potential duration (APD) restitution is widely used to predict dynamics of VF. Restitution of APD is a multi-modal phenomenon, with contributions from previous diastolic intervals (DI), as well as from activation history. We investigated dynamics of change in APD with contributions from memory by using a feedback-based protocol. A Luo-Rudy ionic model of cardiac activation was used to simulate activation. We used four levels of DI, 150, 450, 700, and 1000 msec, to compose a DI sequence which included all possible switches among these DIs. By abruptly changing the DI after APD reached a steady state, we analyzed the transient dynamics of change in APD. As expected, our results showed that for sufficiently long activation, the steady state of APD was unique for each DI. Transient changes in APD showed an asymmetric pattern that was dependent on direction of change in DI, the absolute level of change and the operating level of APD. These results further support the notion that restitution of APD is a multi-modal phenomenon, and that multiple factors need to be considered in using restitution to predict activation dynamics. PMID- 17271170 TI - Passive propagation of the transmembrane potential into homogeneous cardiac tissue at the externally applied current. AB - Mathematical model of homogeneous cardiac tissue is used to show that externally applied current can create changes of transmembrane potential in long distances from stimulating electrodes. PMID- 17271171 TI - Characterization of anatomically compliant linear cardiac lesions created by the CARDIMA radiofrequency surgical ablation system. AB - This study investigated anatomical cardiac linear lesion characteristics created by the CARDIMA RF surgical ablation system. We developed an in vitro porcine cardiac model that simulates cardiac tissue during an on-pump open chest procedure. We used the INTELLITEMP energy management device to deliver RF energy to an 8 electrode, 8 thermocouple deflectable linear surgical probe, to form curvilinear and linear lesions on porcine myocardium. Ablations were at two target temperatures (70 degrees C and 80 degrees C) and durations (60 sec. and 90 sec.). The results show that this system is capable of forming clinically relevant deep and contiguous lesions of desired length. PMID- 17271173 TI - Characterizing cortical dynamics using a large-scale model of turtle visual cortex. AB - Visual stimuli evoke waves of electrical activity that propagate across the visual cortex of freshwater turtles. The experimental methods used to demonstrate these waves measure the activity of populations of pyramidal cells. However, turtle visual cortex contains pyramidal cells and at least three populations of inhibitory interneurons. This study uses a large-scale model to characterize the time course of activity of each of the major populations of neurons in turtle visual cortex. PMID- 17271172 TI - Analysis of relation between coronary perfusion pressure and the extracted parameters from a ventricular fibrillation ECG signal. AB - This work presents an alternative return of spontaneous circulation (ROSC) estimate using indirectly induced presumption that coronary perfusion pressure (CPP) correlates with the extracted parameter from the ventricular fibrillation (VF) ECG signal. In past studies, it is revealed that successful cardiopulmonary resuscitation (CPR) needs at least 30 approximately 40 mmHg CPP during the aortic diastolic period. In 360 segments derived from 18 test dogs with experimental cardiac arrest of cardiac cause, we analyzed the ability of 4 spectral features of VF before countershock to discriminate or not between segments that correspond to CPP. The median frequency (MF), peak frequency (PF), average segment amplitude (ASA) and maximum segment amplitude (MSA) were studied. After preprocessing the raw data acquired from the specific experimental setup and protocol, we verified CPP is a serious estimate of ROSC, and then we analyzed the extracted parameters corresponding to CPP by multiple regression. In the specific conditional frequency domain (MF: 9.42 approximately 12.42 Hz, PF: 8.71 approximately 13.08 Hz, ASA: > 0.19 mV), CPP is correlated to the extracted parameter with 0.71 +/- 0.05 coefficient of multiple determination (R(2)). The combination of MF, PF, and ASA achieved a 79.47 +/- 3% sensitivity and 41.67 +/- 4% specificity in testing. PMID- 17271175 TI - Developing a petascale neural simulation. AB - Simulations of large neural networks have the potential to contribute uniquely to the study of epilepsy, from the effects of extremely local changes in neuron environment and behavior, to the effects of large scale wiring anomalies. Currently, simulations with sufficient detail in the neuron model, however, are limited to cell counts that are far smaller than scales measured by typical probes. Furthermore, it is likely that future simulations will follow the path that large-scale simulations in other fields have and include hierarchically interacting components covering different scales and different biophysics. The resources needed for problem solving in this domain call for petascale computing- computing with supercomputers capable of 10(15) operations a second and holding datasets of 10(15) bytes in memory. We will lay out the structure of our simulation of epileptiform electrical activity in the neocortex, describe experiments and models of its scaling behavior in large cluster supercomputers, identify tight spots in this behavior, and project the performance onto a candidate next generation computing platform. PMID- 17271174 TI - Hybrid neural networks--combining abstract and realistic neural units. AB - There is a trade-off in neural network simulation between simulations that embody the details of neuronal biology and those that omit these details in favor of abstractions. The former approach appeals to physiologists and pharmacologists who can directly relate their experimental manipulations to parameter changes in the model. The latter approach appeals to physicists and mathematicians who seek analytic understanding of the behavior of large numbers of coupled simple units. This simplified approach is also valuable for practical reasons a highly simplified unit will run several orders of magnitude faster than a complex, biologically realistic unit. In order to have our cake and eat it, we have developed hybrid networks in the Neuron simulator package. These make use of Neuron's local variable timestep method to permit simplified integrate-and-fire units to move ahead quickly while realistic neurons in the same network are integrated slowly. PMID- 17271176 TI - Interaction between cellular voltage-sensitive conductance and network parameters in a model of neocortex can generate epileptiform bursting. AB - We examined the effects of both intrinsic neuronal membrane properties and network parameters on oscillatory activity in a model of neocortex. A scalable network model with six different cell types was built with the pGENESIS neural simulator. The neocortical network consisted of two types of pyramidal cells and four types of inhibitory interneurons. All cell types contained both fast sodium and delayed rectifier potassium channels for generation of action potentials. A subset of the pyramidal neurons contained an additional slow inactivating (persistent) sodium current (NaP). The neurons with the NaP current showed spontaneous bursting activity in the absence of external stimulation. The model also included a routine to calculate a simulated electroencephalogram (EEG) trace from the population activity. This revealed emergent network behavior which ranged from desynchronized activity to different types of seizure-like bursting patterns. At settings with weaker excitatory network effects, the propensity to generate seizure-like behavior increased. Strong excitatory network connectivity destroyed oscillatory behavior, whereas weak connectivity enhanced the relative importance of the spontaneously bursting cells. Our findings are in contradiction with the general opinion that strong excitatory synaptic and/or insufficient inhibition effects are associated with seizure initiation, but are in agreement with previously reported behavior in neocortex. PMID- 17271177 TI - A role for desynchronization of neuronal activity in triggering epileptic seizures in the brain. AB - Recent physiological evidence has suggested that initiation of partial epileptic seizures may be due to a desynchronization rather than hypersynchronization of neuronal communication at a seizure focus. This hypothesis was tested using a computational model of the hippocampal slice possessing a physiologically consistent network structure and behavior. When desynchronization was simulated using either increased inhibition or decreased synaptic connectivity, inhibition was decreased or normal synaptic connectivity was restored. Thus a decrease in neuronal synchronization may provide a trigger for seizure initiation in some types of epilepsies. PMID- 17271178 TI - Automatic spike sorting for neural decoding. AB - While various automated spike sorting techniques have been developed, their impact on neural decoding has not been investigated. In this paper we extend previous Gaussian mixture models and expectation maximization (EM) techniques for automatic spike sorting. We suggest that good initialization of EM is critical and can be achieved via spectral clustering. To account for noise we extend the mixture model to include a uniform outlier process. Automatically determining the number of neurons recorded per electrode is a challenging problem which we solve using a greedy optimization algorithm that selects models with different numbers of neurons according to their decoding accuracy. We focus on data recorded from motor cortex and evaluate performance with respect to the decoding of hand kinematics from firing rates. We found that spike trains obtained by our automated technique result in more accurate neural decoding than those obtained by human experts. PMID- 17271179 TI - Tracking modulation of neural encoding in the natural visual world. AB - Traditional approaches to characterizing the transformation from a visual stimulus to neural response assume that 1) the stimulus is stationary and uncorrelated, and 2) the functional properties of the encoding do not change over time. However, recent studies of sensory function under natural stimulus conditions have demonstrated important features of neural encoding that are in violation of these assumptions. Characterizing the stimulus/response mapping in a natural setting demands a more realistic model of sensory encoding in which stimuli of arbitrary complexity are adaptively filtered into a neural response. To identify the stimulus/response mapping in this context, a new analytic technique must be developed. In this paper, a point process extended recursive least-squares (ERLS) approach to receptive field (RF) estimation is detailed. Simulated and experimental neural responses are used to demonstrate the ability of the ERLS technique to estimate RFs from responses to complex natural stimuli and track adaptation of receptive field properties during a single trial. The ERLS technique lends tremendous flexibility to experimental design, facilitating the investigation of sensory function in the natural environment. PMID- 17271180 TI - Reconstruction of hand movement trajectories from a dynamic ensemble of spiking motor cortical neurons. AB - One of the many challenges in long-term decoding from chronically implanted electrodes involves tracking changes in the firing properties of the neural ensemble while simultaneously reconstructing the desired signal. We provide an approach to this problem based on adaptive point process filtering. In particular, we construct a lock-step adaptive filter built upon stochastic models for: a) the receptive field parameters of individual neurons within the ensemble, b) the biological signal to be reconstructed, and c) the instantaneous likelihood of firing in each neuron given the current state of a) and b). We assessed the ability of this filter to maintain a good representation of movement information in a dynamic ensemble of primary motor neurons tuned to hand kinematics. We simulated a recording scenario for this ensemble, where neurons were continuously becoming lost to the recording device while recordings from other, previously unobserved neurons became available. We found that this adaptive decoding algorithm was able to maintain accurate estimates of hand direction, even after the entire neural population had been replaced multiple times, but that the hand velocity signal tended to degrade over long periods. PMID- 17271181 TI - Principle component feature detector for motor cortical control. AB - Principle component analysis (PCA) was performed on recorded neuronal action potentials from neural ensembles in rat's motor cortex when the rat was involved in a closed-loop real-time brain machine interface (BCI). The implanted rat was placed in a conditioning chamber, but freely moving, to decide which one of the two paddles should be activated to shift the light to the center. It is found that the principle component feature vectors revealed the importance of individual neurons and their temporal dynamics in relation to the intention of activating either left or right paddle. In addition, the first principle component feature has much higher discriminative capability than others although it represents only a few percentage of the total variance. Using the first principle component with the Bayes classifier achieved 90% classification accuracy, which is comparable with the accuracy obtained by a more sophisticated high performance support vector classifiers. PMID- 17271182 TI - Motor adaptation as an optimal combination of computational strategies. AB - To efficiently and accurately manipulate objects, the nervous system must adjust motor commands based on experience. Four major adaptive strategies that could help achieve this goal are: internal model formation of the environmental dynamics, minimizing force, trajectory planning, and selectively stiffening the arm. We measured motor adaptation to a robotic force field with and without a large background force requirement. We then developed a computational model of motor adaptation that allowed the relative contribution of the four strategies to be estimated. Motor adaptation was best modeled as a blend of strategies, with internal model formation playing a greater role when forces were smaller and predictable; impedance control had a higher priority when forces were smaller and unpredictable; force minimization was more important when forces were larger; and trajectory planning was involved in both large and small background force conditions. These results are consistent with the viewpoint that the nervous system effectively seeks to minimize a cost-function containing force, stiffness, and position error terms. PMID- 17271183 TI - A neural network model of contours extraction based on orientation selectivity in the primary visual cortex: applications on real images. AB - The capacity of the primary visual cortex (Vl) to extract salient contours from real black-and-white images is studied using a neural network model of information processing in V1. The model includes the input from the lateral geniculate nucleus, arranged according to the preferred orientation through a Gabor function, a feedforward inhibition from inhibitory interneurons and lateral connections (both excitatory and inhibitory) from the other cortical cells (feedback mechanism). Intracortical excitation is arranged according to experimental data, in order to implement the Gestalt proximity and good continuation criteria. Intracortical inhibition realizes a competitive mechanism among neural groups, to eliminate noise. Simulation results, performed on black and-white images, demonstrate that the network can easily extract salient contours, by suppressing zones of constant luminance and isolated noise, with an acceptable settling time (30-40 ms). The role of intracortical synapses was also analyzed: too excessive extension of intracortical inhibition can suppress small contours, on the other side too reduced intracortical inhibition can cause the appearance of superimposed noise in the image. PMID- 17271184 TI - Accelerating motor adaptation by influencing neural computations. AB - When people learn to reach or step in a novel dynamic environment, they initially exhibit a large trajectory error, which they gradually reduce with practice. The error evolution is well modeled by a process in which the motor command on the next movement is adjusted in proportion to the previous movement's trajectory error. We hypothesized that we could accelerate motor adaptation by transiently increasing trajectory error. We tested this hypothesis by quantifying adaptation to a viscous force field applied during the swing phase of stepping in two conditions. In the first condition, we applied then removed the field for 75 steps each, for four iterations. Subjects adapted to each field exposure with a mean time constant of 3.4 steps. In the second condition, we repeated this experiment, but increased the strength of the field for only the first step in each field exposure. We predicted the field strength increase needed by solving a finite difference equation that described the error evolution. Adaptation was significantly faster when the field was transiently amplified (mean time constant = 2 trials). These results demonstrate that it is possible to increase the rate of adaptation to a novel dynamic environment based on knowledge of the computational mechanisms that underlie adaptation. PMID- 17271185 TI - Linear system analysis of ion channel modulation in rod photoreceptors under dim light conditions. AB - Rod photoreceptors perform the task of night vision. The dynamics of dim light response is mainly determined by non-inactivating potassium Kx channels in the inner segment, manifested by such a feature as high-pass filtering. The L-type Ca2+ channels function as the voltage dependent actuator governing synaptic transmission from rods to the second order cells. Modulation of these ion channels can affect physiological features of rods. We introduced here an analytical approach to construct a linear circuit model of the rod membrane to study the effects of modulation of ion channels on rod function. The effects of tetraethylammonium (TEA) and Zn2+ were analyzed in frequency domain. The obtained results were consistent with the computational and experimental studies, which showed that TEA attenuated the high-pass filtering whereas Zn2+ enhanced it. The role of Ca2+ channels in the dynamics of light response was also investigated to show that the activation gate exhibited a larger impact on the overall frequency response than the inactivation gate. Linearization of ion channels for small perturbations provides an attractive alternative method to quantitatively evaluate the physiological significance of the effects of the modulation of ion channels. The resultant linear system may help reveal important features of neurons which can hardly be obtained otherwise. PMID- 17271186 TI - The feasibility of a functional neuromuscular stimulation powered mechanical gait orthosis with coordinated joint locking. AB - The purpose of this study was to examine the feasibility of a hybrid orthosis for walking after spinal cord injury (SCI) that coordinates the locking and unlocking of knee and ankle joints of a reciprocating gait orthosis (RGO), while injecting propulsive forces and controlling unlocked joints with functional neuromuscular stimulation (FNS). The effectiveness of the hybrid system relative to gait stability and posture were determined in this simulation study. A three dimensional computer model of a hybrid orthosis system (HOS) combining FNS with a RGO incorporating feedback control of muscle activation and coordinated joint locking was developed in Working Model 3D. The simulated hybrid orthosis system achieved gait speeds, stride lengths, and cadences of 0.51 +/- 0.03 m/s, 0.85 +/- 0.04 m, and 72 +/- 4 steps/min respectively, exceeding the performance of other hybrid systems. Forward trunk tilt was found to be necessary during initial step from standing and pro-swing, but posture and stability were significantly improved over FNS-only systems. The results of the model shows that a HOS that coordinates knee and ankle joint locking with electrical stimulation to the paralyzed muscles holds significant advantages over brace- and FNS-only walking systems in terms of enhanced trunk stability and posture. PMID- 17271187 TI - Dynamic control of extracellular environment in in vitro neural recording systems. AB - A technique is presented for rapid fabrication of microfluidic channels on top of multichannel in vitro neural recording electrode arrays. The channels allow dynamic control of transient flow over localized areas of the array. Dorsal root ganglion neurons were integrated into the system. The device was used to demonstrate precise control of the extracellular microenvironment of individual cells on the array. Because the methods presented here are not specific to a particular cell type or neural recording system, the technique is amenable to a wide range of applications within the neuroscience field. PMID- 17271188 TI - Multichannel recording and stimulation of neuronal cultures grown on microstamped poly-D-lysine. AB - We report progress toward designable, reproducible, patterned in vitro neuronal cultures. Cell adhesive proteins were directly microcontact printed on microelectrode arrays (MEAs) used as substrates for hippocampal neurons grown in a defined culture medium. The patterned neuronal network circuits were maintained up to one month. The recorded activity was comparable to that of cultures grown on unpatterned uniform surfaces. Time-locked evoked responses were recorded across the networks. PMID- 17271189 TI - Development of an integrated microelectrode/microelectronic device for brain implantable neuroengineering applications. AB - An ultra-low power analog CMOS chip and a silicon based microelectrode array have been fully integrated to a microminiaturized "neuroport" for brain implantable neuroengineering applications. The CMOS IC included preamplifier and multiplexing circuitry, and a hybrid flip-chip bonding technique was developed to fabricate a functional , encapsulated microminiaturized neuroprobe device. As a proof-of concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, suggesting that the new neuroport can form a prime platform for the development of a microminiaturized neural interface to the brain in a single implantable unit. PMID- 17271190 TI - Flexible neural probes with micro-fluidic channels for stable interface with the nervous system. AB - A flexible neural probe with micro-fluidic channels has been developed. The probe is sufficiently flexible to enable minimally invasive recording. The fluidic channel integrated on the probe is capable of injecting chemicals into neural tissues. In addition, it permits a stable interface with the nervous system. We focus on issues concerning: 1) stable recording with electrodes placed in fluidic channels, 2) improved mechanical stiffness by filling channels with a solid that dissolves in neural tissues, and 3) the probe's application to a nerve regeneration electrode. PMID- 17271191 TI - Effect of bicuculline on the spontaneous and evoked activity of patterned embryonic hippocampal neurons cultured in vitro. AB - Characterization of the spontaneous and evoked activity of patterned biological neural networks and discovery of the underlying mechanisms is a major step towards designing functional networks for biosensor, biocomputing and neural prosthetic applications. Here we report on the addition of bicuculline methiodide, a GABA(A) antagonist, to a low density network of embryonic hippocampal neurons linearly patterned on top of planar microelectrode arrays. Our investigation of the differences in the spontaneous and evoked activities before and after drug addition revealed two distinct behavioral trends. One group of electrodes (Group II) showed a marked increase in spontaneous spike rate, burst rate, and burst duration whereas the other (Group I) was unaffected. Likewise, the reliability of evoked activity was observed to be significantly lower in the presence of bicuculline if the stimulating electrode belonged to Group I as compared with Group II. We discuss how these findings might suggest the existence of cells at various stages of maturity in our culture system. PMID- 17271192 TI - Wide-range, picoampere-sensitivity multichannel VLSI potentiostat for neurotransmitter sensing. AB - Neurotransmitter sensing is critical in studying nervous pathways and neurological disorders. A 16-channel current-measuring VLSI potentiostat with multiple ranges from picoamperes to microamperes is presented for electrochemical detection of electroactive neurotransmitters like dopamine, nitric oxide etc. The analog-to-digital converter design employs a current-mode, first-order single-bit delta-sigma modulator architecture with a two-stage, digitally reconfigurable oversampling ratio for ranging the conversion scale. An integrated prototype is fabricated in CMOS technology, and experimentally characterized. Real-time multi channel acquisition of dopamine concentration in vitro is performed with a microfabricated sensor array. PMID- 17271193 TI - Local field potential measurement with low-power analog integrated circuit. AB - Local field potentials (LFPs) in the brain are an important source of information for basic research and clinical (i.e., neuroprosthetic) applications. The energy contained in certain bands of LFPs in the 10-100 Hz range has been shown to correlate with specific arm movement parameters in nonhuman primates. In the near future, implantable devices will need to transmit neural information from hundreds of microelectrodes, and transcutaneous data transfer will become a significant bottleneck. Here we present a low-power, fully-integrated circuit that performs on-site data reduction by isolating LFPs and measuring their signal energy. The resulting analog VLSI circuit consumes 586 microm x 79 microm of silicon area and dissipates only 5 nanowatts of power. We show that the chip performs similarly to state-of-the-art signal processing algorithms. PMID- 17271194 TI - A bio-amplifier with pulse output. AB - A low-power fully integrated bioamplifier is presented that can amplify signals in the range from mHz to kHz while rejecting large DC offsets generated at the electrode-tissue interface. The novel aspect of this amplifier is that its analog output is represented by a series of pulses which provide a low-power, noise resistant means for coding and transmission. The original analog signal can be reconstructed from the resulting pulse train with 13 bit precision at a remote site where power consumption is not so crucial. The fabricated analog amplifier exhibits a gain of 39.5 dB from 0.3 Hz to 5.4 kHz. The power consumption of the whole system is less than 300 microW/channel from a 5-V supply. The fully integrated system was designed in the AMI 0.6 microm CMOS process and it consumes 0.088 mm(2) channel of chip area. PMID- 17271195 TI - Models of stimulation artifacts applied to integrated circuit design. AB - The goal of this research is to develop a monolithic stimulation and recording system capable of simultaneous, multichannel stimulation and recording. Monolithic systems are advantageous for large numbers of recording sites because they scale better than systems composed of discrete amplifiers. A major problem in recording systems is the stimulation artifact, a transient distortion present after stimulation. In order to improve recording systems, we analyze models of the stimulation artifact. Comparisons between model predictions and physical measurements verify the models. We show that the linear model, suitable for inclusion in circuit simulators, can assist in the design of an integrated recording system capable of artifact removal. The proposed design occupies 18,000 micron(2) and is suitable for monolithic integration. PMID- 17271196 TI - Validation of adaptive threshold spike detector for neural recording. AB - We compare the performance of algorithms for automatic spike detection in neural recording applications. Each algorithm sets a threshold based on an estimate of the background noise level. The adaptive spike detection algorithm is suitable for implementation in analog VLSI; results from a proof-of-concept chip using neural data are presented. We also present simulation results of algorithm performance on neural data and compare it to other methods of threshold level adjustment based on the root-mean-square (rms) voltage measured over a finite window. We show that the adaptive spike detection algorithm measures the background noise level accurately despite the presence of large-amplitude action potentials and multi-unit hash. Simulation results enable us to optimize the algorithm parameters, leading to an improved spike detector circuit that is currently being developed. PMID- 17271197 TI - Wireless multichannel biopotential recording using an integrated FM telemetry circuit. AB - This paper reports on the design, implementation, and testing of wireless multichannel recording microsystems featuring on-chip AC amplification, DC input stabilization, time-division-multiplexing, and wireless FM reconstruction of input biopotentials with frequency contents from 0.05-6 kHz with measured I/O correlation coefficients in the range of 70-94% per channel for spike train input amplitudes of 0.2-2 mV(p-p) while dissipating only 2.2 mW from 3 V. The 4.84 mm(2) IC is fabricated using AMI 1.5 microm 2P2M CMOS process, and is successfully interfaced with a micromachined silicon probe for simultaneous multichannel wireless in vitro recording of simulated neural spikes at 98 MHz with measured I/O correlation coefficients of >80%. PMID- 17271198 TI - Temporary pain relief using transcranial electrotherapy stimulation: results of a randomized, double-blind pilot study. AB - Results of a randomized, double-blind pilot study indicate that transcranial electrotherapy stimulation may be an effective treatment for the temporary reduction of pain in osteoarthritis patients. Presently, the predominant method for pain management is medication. One very different approach is the application of micro- to milliamp current applied to specific areas of the head, resulting in a release of endogenous opioids from pain management regions of the brain. For the pilot study, 64 subjects suffering from osteoarthritis of the knee and/or hip were enrolled. For two weeks prior, then during and after treatment, subject pain was self-assessed using the visual scale (VS). In addition, subjects were globally assessed by a physician. All subjects, device operators and physicians were blinded as to whether subjects were treated with an active or sham device. Data collected from the study indicate both a decrease in VS pain scores and a significant improvement (p = 0.05) in physician assessment in subjects treated with active devices compared to those treated with the sham device. PMID- 17271199 TI - Photovoltaic energy converter as a chipscale high efficiency power source for implanted active microelectronic devices. AB - We report the development of a microscale photovoltaic energy converter which has been designed and implemented to deliver power to CMOS-based microelectronic chips. The design targets the delivery of voltages on the order of 3V with power levels in excess of 10 mW. The geometry of the prototype device, which has been fabricated and tested, is specifically designed for coupling to an optical fiber, to facilitate remote power delivery in implantable component environment. PMID- 17271201 TI - Biofuel cells: a possible power source for implantable electronic devices. AB - Biofuel cells were designed to investigate electricity production from Escherichia coli and human white blood cells as a preliminary investigation into the possible future use of such fuel cells as power sources for implantable electronic devices. The biofuel cell's function is based on the coupling of glucose oxidation to the reduction of oxygen to water. It might, therefore, be possible to utilize the cellular processes involved in oxidative metabolism to generate electrical energy for numerous medical applications. In the bacteria experiment, we were able to generate small electrical currents, which gradually decreased over a (2) hour measurement period. In the human white blood cell experiment, our biofuel cell attained current outputs, which were smaller in magnitude than values recorded from the microbial biofuel cell. PMID- 17271200 TI - A test microchip for evaluation of hermetic packaging technology for biomedical prosthetic implants. AB - The development of a test chip that will be used to evaluate a hermetic and biocompatible package for the driving CMOS circuitry of a retinal prosthesis is described. The package design is estimated to be about 2 x 2 x 0.3 mm(3) and will be formed by conformal layers of parylene and a metal (e.g. titanium) as inner and outer protections, respectively. The test chip has been specifically designed for evaluation of the packaging technology. It consists of many blocks of analog and digital components as well as relative humidity and temperature sensors. The test chip has more probe points than a typical chip, allowing a more thorough evaluation of circuit behavior during the testing. This chip will first be coated in a layer of parylene C and soaked in heated isotonic saline for an extended period of time. Every block in the chip will then be tested for functionality using the surface probe points. The next step is to coat the surface of another test chip with parylene and a metal and repeat these soak tests. The results will then be analyzed and mean time-to-failure for the different samples will then be computed. Using the accelerated testing paradigm, these results will then be extrapolated to mean time-to-failure in the operating intraocular environment. Parylene test structures have already undergone an accelerated lifetime test and results have been analyzed. PMID- 17271202 TI - A multi-functional online measurement system for neuron-microelectrode interface study. AB - The goal of this paper is to develop a multifunctional measurement system for neuron-microelectrode interface study by LabVIEW. The system uses a commercial 60 channel microelectrode array (MEA) as an interface platform. These online functions of neuronal stimulation, extracellular potential recording, impedance monitoring, and data storage have been integrated into this system. Two offline analysis functions of wavelet de-noising and artifact removing are also included. The former two online functions are executed respectively by a NI-DAQ card and by a self-made analog frond-end amplifier, and Agilent 4284A LCR meter makes the impedance measurement. We have completed the basic functional verifications on a cultured MEA with PC-12. PMID- 17271203 TI - Bias voltages at microelectrodes change neural interface properties in vivo. AB - Rejuvenation of iridium microelectrode sites, which involves applying a 1.5 V bias for 4 s, has been shown to reduce site impedances of chronically implanted microelectrode arrays. This study applied complex impedance spectroscopy measurements to an equivalent circuit model of the electrode-tissue interface. Rejuvenation was found to cause a transient increase in electrode conductivity through an IrO2 layer and a decrease in the surrounding extracellular resistance by 85 +/- 1% (n=73, t-test p < 0.001) and a decrease in the immediate site resistance by 44 +/- 7% (n=73, t-test p<0.001). These findings may be useful as an intervention strategy to prolong the lifetime of chronic microelectrode implants for neuroprostheses. PMID- 17271204 TI - A novel system design for implantable stimulator application. AB - In this paper, we present a novel and implantable micro-stimulator design. Instead of generating the stimulating pulses by using the conventional computerized controller such as FPGA or MCU, the pulse width modulation (PWM) has been used to control the stimulation. The proposed system need not program the computerized controller, so it simplifies the circuit complexity and achieves the low-cost issue. The proposed micro-stimulator chip has a 5-bits programmable current selectivity and uses pulse width modulation skill to adjust the pulse width. Besides, the system has four different stimulation frequencies to be chosen and provides normal, random, and burst stimulation pulses for the practical situation. PMID- 17271205 TI - Optimization of an implantable volume conduction antenna. AB - As implantable devices become increasingly sophisticated, there is a strong need for developing a wireless data communication channel between these devices and external computers. This important problem has been studied and an antenna is being designed based on the volume conduction of biological tissues. Closed-form equation and finite element analyses were performed for the case of brain implantation using a spherical volume conduction model of the head. Finite element proofs of concept in 2D and 3D demonstrated the influence of epoxy and a volume conductor reflector on volume currents, exhibiting changes in the far field as controlled by the near field. A 3D finite element analysis showed an increased signal transduction of 35% as compared to the 3D analytical analysis, which was not able to simulate the epoxy. The optimum angle of inclination is shallower than what was intuitively thought, indicating that the antenna elements destructively interfere with the generated surface voltages, requiring the antenna elements to be rotated away from each other. PMID- 17271206 TI - Multielectrode impedance tuning: reducing noise and improving stimulation efficacy. AB - Multielectrode arrays (MEAs) have emerged as a leading technology for extracellular, electrophysiological investigations of neuronal networks. The study of biological neural networks is a difficult task that is further confounded by mismatches in electrode impedance. Electrode impedance plays an important role in shaping incoming signals, determining thermal noise, and influencing the efficacy of stimulation. Our approach to optimally reduce thermal noise and improving the reliability of stimulation is twofold minimize the impedance and match it across all electrodes. To this aim, we have fabricated a device that allows for the automated, impedance-controlled electroplating of micro-electrodes. This device is capable of rapidly (minutes) producing uniformly low impedances across all electrodes in an MEA. The need for uniformly low impedances is important for controlled studies of neuronal networks; this need will increase in the future as MEA technology scales from tens of electrodes to thousands. PMID- 17271207 TI - Utilizing remaining voluntary muscle synergies to control FES elbow extension after spinal cord injury. AB - Individuals with a C5/C6 spinal cord injury (SCI) have paralyzed elbow extensors, yet retain weak to strong voluntary control of elbow flexion and some shoulder movements. They lack elbow extension, which is critical during activities of daily living. This research focuses on development of a synergistic controller employing remaining voluntary elbow flexor and shoulder electromyography (EMG) to control elbow extension with functional electrical stimulation. We hypothesized that remaining voluntarily controlled upper extremity muscles could be used to train an artificial neural network (ANN) to control stimulation of the paralyzed triceps and provide functional benefits. Surface EMG was collected from SCI subjects while they produced isometric endpoint force vectors of varying magnitude and direction using triceps stimulation levels predicted by a biomechanical model. ANN'S were trained with the collected EMG and stimulation levels. The best set of muscles inputs was selected for each subject such that trained networks yielded low error, minimized the required number of EMG inputs, and effectively learned relationships between endpoint force and triceps stimulation. The synergistic controller increased the range of force vectors, provided discrete forces, and enabled an overhead reach task. PMID- 17271208 TI - An adaptive M-wave canceler for the EMG controlled functional electrical stimulator and its FPGA implementation. AB - Biopotential signals have been used as command and feedback signals in systems using electrical stimulation of motor nerves to restore the lost function. In order to use the voluntary electromyography (EMG) as a control signal for the functional electrical stimulation of the same muscle, it is necessary to suppress the M-wave evoked by the electrical stimulation. We present a Gram-Schmidt (GS) prediction error filter which effectively eliminates the M-wave from voluntary EMG. The GS filter has systolic array structure, so it offers advantages for the real-time processing on the field programmable gate array (FPGA). On basis of the data obtained from model for M-wave and voluntary EMG and from CNS injury patient, the proposed GS filter showed a very promising performance. PMID- 17271209 TI - Closed-loop neural control of cursor motion using a Kalman filter. AB - Recently, we proposed a Kalman filter method to model the probabilistic relationship between neural firing in motor cortex and hand kinematics. In this paper, we demonstrate on-line, closed-loop, neural control of cursor motion using the Kalman filter. In this task a monkey moves a cursor on a computer monitor using either a manipulandum or their neural activity recorded with a chronically implanted micro-electrode array. A number of advantages of the Kalman filter were explored during the on-line tasks and we found that the Kalman filter had superior performance to previously reported linear regression methods. While the results suggest the applicability of the Kalman filter for neural prosthesis applications, we observed the decoded cursor position was noisier under brain control as compared with manual control using the manipulandum. To smooth the cursor motion without decreasing accuracy we propose a method that smoothes the neural firing rates. This smoothing method is described and its validity is quantitatively evaluated with recorded data. PMID- 17271210 TI - A noninvasive functional electrical stimulation system with patient-driven loop for hand function restoration. AB - In this study, a noninvasive functional electrical stimulation (FES) system is proposed to restore hand functions. The control strategy of this system is based on the patient-driven control loop. The patient can use his sound extremity to control FES system to generate the electrical stimulation so that the paralyzed muscles will be excited. In addition, electromyographic (EMG) signals, which are recorded by the sensors in the electrical stimulator, can serve as the trigger for the initialization of the system and the adjustment of the electrical stimulation parameters. From the preliminary results, they show that the subjects can successfully control the proposed system. We hope that patients will benefit a lot from this kind of FES system with patient-driven control loop. PMID- 17271211 TI - Adaptive neural network controller for an upper extremity neuroprosthesis. AB - The long term goal of this project is to develop an adaptive neural network controller for an upper extremity neuroprosthesis targeted for people with C5/C6 spinal cord injury (SCI). The challenge is to determine how to simultaneously stimulate different paralyzed muscles based on the EMG activity of muscles under retained voluntary control. The controller extracts the movement intention from the recorded EMG signals and generates the appropriate stimulation levels to activate the paralyzed muscles. To test the feasibility of this controller, different arm movements were recorded from able bodied subjects. Using a musculoskeletal model of the arm, inverse simulations provided muscle activation patterns corresponding to these movements. The model was modified to reflect C5/C6 SCI and the optimization criteria were varied to reflect different nervous system motor control strategies. Activation patterns were then used to train a time-delayed neural network to predict paralyzed muscle activations from voluntary muscle activations. Forward simulations were performed to obtain predicted movements and use the kinematic errors to design an adaptive strategy to account for disturbances and changes in the system. PMID- 17271212 TI - Intraoperative testing of selectivity of spiral nerve cuff electrodes. AB - Nerve cuff electrodes were used intraoperatively to stimulate peripheral nerves to test electrode selectivity in the human upper extremity. Subjects were recruited from patients undergoing upper extremity nerve repair procedures. The nerves were stimulated through different contacts in the cuff and with varying parameters. Estimates of threshold and selectivity data were recorded. The stimulation thresholds found were an order of magnitude higher than prior animal studies using the spiral nerve cuff electrode. Preliminary selectivity was found on the ulnar nerve and the upper trunk of the brachial plexus of one subject. The biceps and pectoralis major were selectively activated by a single cuff placed proximally, on the upper trunk; the flexor carpi ulnaris and first dorsal interosseous were selectively activated by a single cuff placed on the ulnar nerve. PMID- 17271213 TI - "Safe" charge-injection waveforms for iridium oxide (AIROF) microelectrodes. AB - Use of anodic bias improves the charge-injection limits of activated iridium oxide (AIROF) microelectrodes. Asymmetric waveforms, in which the charge balancing anodic phase is delivered at a lower current density and longer pulse width, has been found to allow for higher values of anodic bias voltages, thus maximizing the AIROF charge-injection capacity. Limiting the voltage excursion of the AIROF below the value at which electrolysis of water occurs is essential to maintaining the long-term viability of implanted electrodes. However, maintaining the electrodes at an anodic bias state while keeping the electrode voltage within these electrochemically "safe" limits complicates the topology of the electronic driver circuitry. We present two possible driver topologies that use compliance voltage limitation in combination with cathodic current modification. PMID- 17271214 TI - Electrode array for reversing the recruitment order of peripheral nerve stimulation: a simulation study. AB - Electrical stimulation of peripheral nerve activates large-diameter fibers before small ones. Previous studies using computer simulations and animal experiments showed that selective activation of small fibers could be achieved using an array of four cathodes and five anodes to reshape the extracellular voltage along the nerve and that the technique was independent of stimulating pulse width. In this simulation study, electrode arrays of 5, 7, 9, and 11 contacts were tested using finite element model of ventral sacral root. Contact separation of the array was 0.75 mm. The 5-contact array activated small axons having internodal distance smaller than contact separation before larger axons (< 7.5 microm in this case). Arrays of 7, 9 and 11 contacts suppressed the excitability of axons having internodal distance close to the intercathodic distance ( approximately 15 microm in this case). The recruitment orders were identical for 50 micros and 200 micros pulse stimulations. Simulations suggested that electrode arrays of 5 and 7 contacts could be used to achieve selective activation of small axons independently of stimulating pulse width. Arrays of 5 and 7 contacts also decreased the recruitment curve slope to 43% and 72% of the tripolar electrode. PMID- 17271215 TI - A batch-manufacturable uniform current density metallic-shell hemispherical microelectrode. AB - In this paper, we report on the simulation results for a batch-manufacturable uniform current density metallic-shell hemispherical microelectrode. These electrodes can be used for safe stimulation of neurons or neuromuscular junctions in a variety of research and clinical (neural prostheses) settings. Maxwell 3D software package was used to simulate several microelectrode structures capable of providing a uniform current density profile. These included recessed planar, solid-metallic and metallic-shell hemispherical microelectrodes. Simulation results showed no significant difference between the solid metallic and metallic shell hemispherical electrodes with the latter being more compatible with the integrated circuit and MEMS microfabrication technologies. In addition, both hemispherical microelectrodes yield improved current density distribution and profile compared with the recessed planar electrode. PMID- 17271216 TI - Sputtered iridium oxide films (SIROFs) for low-impedance neural stimulation and recording electrodes. AB - Iridium oxide films formed by electrochemical activation of iridium metal (AIROF) or by electrochemical deposition (EIROF) are being evaluated as low-impedance charge-injection coatings for neural stimulation and recording. Iridium oxide may also be deposited by reactive sputtering from iridium metal in an oxidizing plasma. The characterization of sputtered iridium oxide films (SIROFs) as coatings for nerve electrodes is reported. SIROFs were characterized by cyclic voltammetry, electrochemical impedance spectroscopy, and potential transient measurements during charge-injection. The surface morphology of the SIROF transitions from smooth to highly nodular with increasing film thickness from 80 nm to 4600 nm. Charge-injection capacities exceed 0.75 mC/cm(2) with 0.75 ms current pulses in thicker films. The SIROF was deposited on both planar and non planar substrates and photolithographically patterned by lift-off. PMID- 17271217 TI - Finite element analysis of a microelectrode on a substrate. AB - Analytical solutions for the voltage field generated by a microelectrode are available for simple electrode and volume conductor geometries. However, the practical microelectrodes fabricated on a planar substrate deviate from those simple geometries substantially. It needs to be determined in which cases the analytical methods can be employed without introducing significant errors. We developed a finite element model (FEM) to study the potential field generated in a volume conductor by a circular disk electrode etched into a planar substrate. The results were compared to that of an analytical model provided by Wiley and Webster. The peak voltage at the contact surface varies as a function of the substrate width and it reaches 90% of the maximum at about twice the contact diameter. This suggests that an FEM is required for narrow substrate widths. The effect of the intercontact distance for the bipolar electrodes is also studied. PMID- 17271218 TI - Stimulus induced pH changes in retinal implants. AB - Electrical stimulation of neural tissue requires charge injection into the biological environment. This is achieved through both Faradaic and non-Faradaic reactions at the electrode/tissue interface. Some Faradaic reactions have the potential to dramatically alter pH levels, leading to tissue damage. The present study looked to investigate the effects of stimulus induced pH changes for a variety of stimulation parameters in a retinal implant. Electrodes were stimulated using monophasic and biphasic pulses at different intensities and in different mediums. Stimulus frequency and pulse width were maintained consistent for all tests. pH levels were recorded using a pH microelectrode and verified using a pH color indicator (phenol red). As expected, no significant pH change could be detected in buffered saline or balanced salt solution. However, stimulation parameters causing pH changes could be detected in unbuffered saline solution. While electrode stimulation using biphasic charge-balanced current pulses showed minimal pH change, stimulation using monophasic pulses showed significant pH shifts. The extent of pH change was related to duration of stimulation. The results from this study provide an insight to the electrochemical mechanisms at the interface of the electrolyte medium and retinal stimulation electrodes. PMID- 17271219 TI - Vision rehabilitation with the optic nerve visual prosthesis. AB - A blind volunteer with retinitis pigmentosa has been chronically implanted with an optic nerve visual prosthesis. The axons of retinal ganglion cells have been successfully activated by electrical stimuli to evoke many distinct phosphenes over a large portion of the visual field. No sensations other than visual have been elicited. Controlled electrical stimulation of the optic nerve proved able to convey visual information useful for the localization and discrimination of objects. PMID- 17271220 TI - Towards photosensor movement--adaptive image analysis in an electronic retinal prosthesis. AB - By way of extracellular, stimulating electrodes, electronic vision prosthesis aims to render discrete light spots--so-called phosphenes--in the visual field, thereby providing a phosphene image serving as a rudimentary remediation of profound blindness. It is proposed that a digital camera, or some other photosensitive array, captures frames, the frames be analyzed, and phosphenes be actuated accordingly. We present a numerical experiment wherein we observed the phosphene image in response to a set of stimuli for various image analysis schemes. We used the mutual-information function to quantify the efficacy of analysis schemes; the function penalizes a scheme for introducing redundancy to the phosphene image, while accounting for the probability of each stimulus. We demonstrate an effective scheme involving Laplacian of Gaussian (nabla(2)G) kernels geometrically transformed in accordance with phosphene layout. Further, we propose adapting the kernels comprising a scheme in accordance with photosensor movement. PMID- 17271221 TI - Intraocular impedance as a function of the position in the eye, electrode material and electrode size. AB - A critical element of a retinal prosthesis is the electrode assembly, which is placed on the retina. It is via this interface that the nerve cells are stimulated to produce the perception of light. The electrode impedance is an integral part in determining the design of the stimulating electrode and the attached circuit. The impedances involved are not only the tissue impedance but the electrode itself contributes to the impedance. Further on the electrode impedance depends not only the material of the electrode but also the size of the electrode. This paper discusses the results obtained by the intraocular impedance measurements with varying electrode size, electrode material and position of the electrode within the eye. PMID- 17271222 TI - Visual task performance in blind humans with retinal prosthetic implants. AB - A prototype electronic retinal prosthesis has been tested in three subjects. The system features an implanted retinal stimulator and an external system for image acquisition, processing, and telemetry. The subjects in general performed better than chance on psychophysical tests involving object detection, object counting, object discrimination, and direction of movement. PMID- 17271223 TI - An efficient multiplexing method for addressing large numbers of electrodes in a visual neuroprosthesis. AB - Recent clinical trials using modified cochlear implants employ a small number of electrodes to stimulate surviving retinal neurons in blind patients and indicate that spatially-mapped phosphenes may indeed be elicited through these means. The next obvious step forward in the path toward achieving a useful visual prosthesis for the blind will be to increase the quantity of stimulation sites such that shapes, characters and rudimentary images may be conveyed. An important objective that must be obtained in the pursuit of this task is the ability to configure and deliver the stimulation with sufficient speed so as to avoid delays that are perceived by the patient as flicker within the visual scene. As the quantity of electrodes within the prosthesis increases, so too does the complexity of achieving this objective. This paper describes a means through which large numbers of electrode sites may be efficiently addressed in a neurostimulation circuit so as to increase the rate at which said circuit may be configured for the delivery of stimulation. PMID- 17271224 TI - Development of an inductively coupled epiretinal vision prosthesis. AB - Electrical stimulation of the retina elicits visual perception in patients with retinitis pigmentosa. Using the potentials of microsystem technology, neural prostheses to restore vision become feasible that are completely implantable in the eye. In this paper, we describe the development of an inductively coupled epiretinal vision prosthesis. Microelectronic chips for data encoding and stimulation were assembled on flexible substrates with an integrated electrode array. The system was encapsulated with parylene C and silicone rubber. The receiver part was placed into an artificial intraocular lens. Microcables led to the stimulation array in the macula region. This prototype elicited spatio temporal patterns in the visual cortex after electrical stimulation of the retina in the cat. PMID- 17271225 TI - RF-powered BIONs for stimulation and sensing. AB - Virtually all bodily functions are controlled by electrical signals in nerves and muscles. Electrical stimulation can restore missing signals but this has been difficult to achieve practically because of limitations in the bioelectric interfaces. Wireless, injectable microdevices are versatile, robust and relatively inexpensive to implant in a variety of sites and applications. Several variants are now in clinical use or under development to perform stimulation and/or sensing functions and to operate autonomously or with continuous coordination and feedback control. PMID- 17271226 TI - Rehabilitation of the arm and hand following stroke--a clinical trial with BIONs. AB - This paper reports the clinical experiences and preliminary observations from implanted microstimulators used to reduce some impairments following a stroke. Ongoing research protocols to reduce shoulder subluxation and hand contractures using BION stimulation are described. Comparison of compliance and patient satisfaction between individuals exercising at home with surface stimulation and implanted stimulation are characterized. The effectiveness of the two home based stimulation programs are compared. PMID- 17271227 TI - BIONic WalkAide for correcting foot drop. AB - The goal of this study was to test the feasibility and efficacy of using microstimulators (BIONs) to correct foot drop, the first human application of BIONs in functional electrical stimulation (FES). A prototype BIONic foot drop stimulator was developed by modifying a WalkAide2 stimulator to control BION stimulation of the ankle dorsiflexor muscles. BION stimulation was compared with surface stimulation of the common peroneal nerve provided by a normal WalkAide2 foot drop stimulator. Compared to surface stimulation, we found that BION stimulation of the deep peroneal nerve produces a more balanced ankle flexion movement without everting the foot. A 3-D motion analysis was performed to measure the ankle and foot kinematics with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. The BIONic WalkAide elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the unaffected leg. The physiological cost index (PCI) was used to measure effort during walking. The PCI is high without stimulation (2.29 +/- 0.37; mean +/- S.D.) and greatly reduced with surface (1.29 +/- 0.10) and BION stimulation (1.46 +/- 0.24). Also, walking speed is increased from 9.4 +/- 0.4 m/min. without stimulation to 19.6 +/- 2.0 m/min. with surface and 17.8 +/- 0.7 m/min. with BION stimulation. We conclude that functional electrical stimulation with BIONs is a practical alternative to surface stimulation and provides more selective control of muscle activation. PMID- 17271228 TI - Rechargeable battery-powered bion microstimulators for neuromudulation. AB - The rechargeable battery-powered bion microstimulator is designed to bring neurostimulation to mainstream medicine and improve the quality of life of those suffering from neurological disorders. The bion, through direct electrical stimulation of excitable tissues, is intended to treat numerous disorders including urinary urge incontinence, fecal incontinence, chronic headaches, peripheral pain, angina and obstructive sleep apnea. The rechargeable bion microstimulator, manufactured by Advanced Bionics Corporation, is designed to be implanted using a minimally invasive approach that would appeal to clinicians of different specialties as well as patients suffering from a wide variety of debilitating conditions. The bion is currently in clinical trials for the treatment of urinary urge incontinence and headaches. Other clinical trials are expected to follow in the future. PMID- 17271229 TI - A multichannel monolithic wireless microstimulator. AB - A 64-site wireless current microstimulator chip (Interestim-2B) and a prototype implant based on this chip have been developed for neural prosthesis applications. Modular stand-alone architecture allows up to 32 such chips to be connected in parallel to drive 2048 sites. The only off-chip components are a receiver inductive-capacitive (LC) tank and microelectrode arrays such as silicon probes for intracortical stimulation. The implant receives inductive power and data at 2.5 Mb/sec from a frequency shift keyed carrier to generate up to 65,800 stimulus pulses/sec. Each chip contains 16 current drivers with 270 microA full scale current, 5-bit resolution, 100 MOmega output impedance, and a dynamic range that extends within 150 mV of the 5 V supply rail. The chip and implant (without probes) measure 4.6 x 4.6 x 0.5 and 19 x 14 x 6 (mm), respectively. PMID- 17271230 TI - Effect on prosthetic vision visual acuity by filtering schemes, filter cut-off frequency and phosphene matrix: a virtual reality simulation. AB - Visual acuity of prosthetic vision was examined under virtual reality simulation. Prosthetic vision was simulated by first filtering an image using circular mean filters or Gaussian smoothing filters of different cut-off frequencies. Pixel values at 100 fixed sites of the filtered image were taken, sampling either with a regular rectangular or hexagonal matrix. Each pixel value was transformed into a Gaussian intensity profile centered at the corresponding position at which the sample was taken to simulate the evoked visual effect of an electric stimulation. Visual acuity scores of three subjects, each completing two sets of results, were recorded across different filtering schemes, cut-off frequencies and sampling matrices. The best mean score recorded was 1.55 logMAR, with the worst being 1.70 logMAR. The difference was mostly attributed to filter cut-off frequency. Differences between filtering schemes were insignificant. Results also showed emerging trends demonstrating differences between rectangular and hexagonal sampling matrices. PMID- 17271231 TI - A perception-based processing strategy for cochlear implants and speech coding. AB - We propose a perception-based signal processing strategy to encode slowly-varying amplitude and frequency modulations within a frequency analysis band. We have simulated a four-band version of this processor and showed that vowel recognition is improved by adding frequency modulation, particularly in noise. This strategy can be used to efficiently encode fine structure in cochlear implants and to improve speech recognition in noise. Because the center frequency is removed in the analysis, this technique also has the potential to provide high-quality, low bit speech coding and synthesis. PMID- 17271232 TI - A new modified multi-electrode stimulation method for ECAP recording in cochlear implant. AB - Cochlear implant systems are based on stimulation of the auditory nerve fibers by electrical current with implanted electrodes. In the clinical tests, based on stimulation by electrical current and recording the evoked compound action potential (CCAP) same as neural response telemetry (NRT), electrical behavior and population distribution of the nerve fibers can be evaluated. Stimulation parameter in mimicking the normal hearing can be determined by the results of these tests. Condition of these tests is different from the actual stimulation for hearing, both in amplitude and time sequence of the stimulation current pulses. Therefore, there are some problems in the mapping the test results to stimulation parameters. At this paper, we have presented a new selective nonsimultaneous multi-electrode stimulation (NSMES) method based on applying the inhibitory pre-pulses by lateral electrodes that changes the initial conditions of the fibers to focus on the target fibers. The results of simulations show that this method will penalize undesired population distribution of the remained excitable fibers and it has been distinguished from the desired one. To estimate the electrical behavior of the fibers in normal use of the system for hearing, which has much more pulse rate than the test condition, we assumed a probabilistic function for recovery time of the fibers to map the test results to hearing condition parameters. Simulation results show that the stimulation electrode array parameters can be determined more accurately by the presented modification qualitatively and quantitatively. PMID- 17271233 TI - Detecting the onset of hyper-reflexive bladder contractions from pudendal nerve electrical activity. AB - Individuals with spinal cord injury or neurological disorders may develop involuntary bladder contraction at low volumes (bladder hyper-reflexia), which can lead to significant health problems. Current devices can eliminate nascent contractions through continuous stimulation, but do not have a means to detect the onset of bladder contraction to stimulate conditionally. The objective of this study is to determine the relationship between the electrical activity of the pudendal nerve (PNT) and hyper-reflexive bladder contraction, and to use the relationship to develop an algorithm to detect the onset of a bladder contraction. Bladder pressure and PNT ENG were recorded in six intact male cats. There were bursts of neuronal activity in the PNT during bladder contractions. An algorithm was developed to detect the onset of a bladder contraction using the PNT ENG activity. The algorithm calculated the onset of bladder contraction on average 2.8 seconds after the contraction started with an average increase in pressure of 14.0 cmH2O. There existed a phasic relationship between the bladder and the PNT ENG, which enabled the algorithm to detect the onset of a bladder contraction. The PNT ENG can be used as a trigger to deliver conditional inhibitory stimulation of the bladder. PMID- 17271234 TI - Ultrasonically-assisted intracortical microstimulation of the rat. AB - High frequency tone bursts of ultrasound are capable of increasing the sensitivity of rat motor cortex to electrical stimulation. In this study, 11.75 MHz ultrasound pre-stimuli were delivered to the forelimb motor region of the rat cortex followed by an electrical pulse train to assess changes in cortical activation. The temporal peak intensity of the ultrasound delivered to the brain ranged from 100 to 150 W/cm(2). Tone bursts of 10 to 50 ms in duration were delivered once per second over periods of 30 to 240 seconds. The intracortical microstimulation (ICMS) current needed for forepaw motor response decreased by as much as 40% when applying 50 ms ultrasound pulses. Brain excitability changes were seen with a thermal index (TI) as low as 2.0. Ultrasound application alone was not able to induce motor responses. PMID- 17271235 TI - Characteristics of stapedius muscle electromyograms elicited by cochlear implant stimulation in the rat. AB - The electrical stapedius reflex (ESR) threshold, detected by eardrum acoustic impedance change, is strongly correlated with cochlear implant recipients' behavioral comfort levels. However reports suggest acoustic impedance changes are not detectable in 30-40% of patients. The goals of this study were to develop an animal model and investigate the characteristics of the stapedius muscle electromyogram (SEMG) elicited by a cochlear implant, as an alternative measure of ESR activation. Bipolar tungsten micro wire electrodes recorded the SEMG signal from the stapedius muscle of 6 rats. The cochlea was implanted with a multichannel intracochlear electrode that delivered biphasic electrical pulses. Maximum SEMG potentials were 20-500 microV (mean: 174 microV) or 8-42 dB SNR (mean: 24 dB). The dynamic range of the responses that reached saturation were approximately 10 dB, with threshold inversely dependent on pulse-width and electrode separation. The electrical brainstem response (EABR) threshold was 5.6 dB lower than the ESR threshold on average, but the standard deviation was relatively high (2.4 dB), suggesting that these two signals could provide independent information for objective cochlear implant fitting. Post-operative SEMGs were recorded in several animals; including one animal for up to 63 days. The results suggest the overall feasibility of the approach for objective cochlear implant fitting. PMID- 17271236 TI - Microwave radiation has modulation frequency dependent stimulating effect on human EEG rhythms. AB - This study is focused on low-level modulated microwave field effects on human EEG theta, alpha and beta rhythms at different modulation frequencies. During the experiment 13 healthy volunteers were exposed to a microwave (450 MHz) with 7 Hz, 14 Hz and 21 Hz frequency on-off modulation. The field power density at the scalp was 0.16 mW/cm(2). The experimental protocol consisted of five cycles of the repetitive microwave stimulation at fixed modulation frequencies. Changes in the EEG rhythms energy became evident in the case of modulation frequencies higher than the EEG rhythms frequencies. The changes varied strongly from subject to subject. Microwave exposure caused statistically significant changes in the EEG theta rhythm energy and for occipital channels in the alpha rhythm energy. PMID- 17271237 TI - Neurite extension from rod bipolar cells in retinal cell and explant cultures. AB - One of the key requirements for the success of a subretinal prosthesis or photoreceptor transplant is the formation of an effective interface with the remaining neural retina. An optimal interface would be one where specific and highly efficient contacts were made with retinal neurons, presumably bipolar cells. Although the properties of neurite (particularly axonal) outgrowth have been extensively studied in retinal ganglion cells, comparatively little work has been done with other retinal neurons. The goal of the present research is to explore the survival and neurite outgrowth properties of a specific type of retinal cell, the rod bipolar cell (RBC), using in vitro culture preparations. RBCs are the most numerous of the several classes of bipolar cells in mammals, and would be a likely target of stimulation by any subretinal implant. We report here that RBCs in short term culture--as isolated cells or within retinal explants--extend their dendrites, and that these are often decorated with varicosities and smaller spine-like extensions. This response is similar to remodeling of RBCs observed in cat models of retinal detachment, and suggests it might be possible to manipulate RBCs with appropriate growth and guidance cues to form an optimal interface with subretinal devices or transplants. PMID- 17271238 TI - Encoding of self-paced, repetitive forelimb movements in rat primary motor cortex. AB - Multi-unit, intra-cortical recordings from the primary motor cortex have been shown to provide information about functional movement of the body, and thus, have been used as command signals for control of an external robotic arm in rat and monkey. However, study of the M1 responses has shown that movement encoding may be dependent on both the functional and behavioral context of the intended motion. The main objective of the present work was to determine if self-paced, repetitive forelimb movements are effectively encoded in multiple-unit recordings from the primary motor cortex (M1) in freely moving, non-constrained rats. Four rats were chronically implanted with 7-channel, 50 microm tungsten micro-wire arrays. Standard psychophysical techniques were first used to train the rats to depress a response paddle in return for a food reward. We computed peri-event time histograms and found both statistically significant excitatory (24/49) and inhibitory (9/49) pre-paddle activity up to 200 ms before a paddle hit. On average, responses from 161+/-37 individual paddle hits were necessary in order to detect statistically significant (> 95%), excitatory pre-paddle action. Thus, while it is possible to detect self-paced, forelimb movements in multi-unit recordings of M1, the high number of repetitions required would limit the efficacy of a real-time cortical neuroprosthesis. PMID- 17271240 TI - An artificial neural network approach to predicting arm movements from ECoG. AB - There are three specific aims. First, demonstrate the practicality of using an artificial neural network based approach to correlate these cortical signals with actual and imagined arm movements. Second, to identify areas of the cortical surface that provide the most useful command information. Third, quantify the information content and information transfer rate of the signals obtained from the subdural grids relative to a set of relevant arm movements. This work presents progress toward these aims. PMID- 17271239 TI - Power feasibility of implantable digital spike-sorting circuits for neural prosthetic systems. AB - A new class of neural prosthetic systems aims to assist disabled patients by translating cortical neural activity into control signals for prosthetic devices. Based on the success of proof-of-concept systems in the laboratory, there is now considerable interest in increasing system performance and creating implantable electronics for use in clinical systems. A critical question that impacts system performance and the overall architecture of these systems is whether it is possible to identify the neural source of each action potential (spike sorting) in real-time and with low power. Low power is essential both for power supply considerations and heat dissipation in the brain. In this paper we report that several state-of-the-art spike sorting algorithms implemented in modern CMOS VLSI processes are expected to be power realistic. PMID- 17271241 TI - A 96-channel neural stimulation system for driving AIROF microelectrodes. AB - We present the design and testing of a 96-channel stimulation system to drive activated iridium oxide (AIROF) microelectrodes within safe charge-injection limits. Our system improves upon the traditional capacitively coupled, symmetric charge-balanced biphasic stimulation waveform so as to maximize charge-injection capacity without endangering the microelectrodes. It can deliver computer controlled cathodic current pulse for to up to 96 AIROF microelectrodes and positively bias them during the inter-pulse interval. The stimulation system is comprised of (1) 12 custom-designed PCB boards each hosting an 8-channel ASIC chip, (2) a motherboard to communicate between these 12 boards and the PC, (3) the PC interface equipped with a DIO card and the corresponding software. We plan to use this system in animal experiments for intracortical neural stimulation of implanted electrodes within our visual prosthesis project. PMID- 17271242 TI - Characterization of ankle function during stair ambulation. AB - The aim of this study was to examine the ankle joint during level walking, stair ascent, and stair descent to determine models for use in the design of prosthetic and orthotic systems. Ten healthy subjects were asked to walk (1) across a level walkway, (2) up, and (3) down an instrumented stairway. Sagittal plane kinematic and kinetic data were analyzed to obtain ankle biomechanics during the stance phase of each task. Each stance phase was broken down into sub-phases based on the power trajectory. The ideal model was taken to be the simplest combination of mechanical elements (springs, dampers, and torque actuators) that could reproduce the patterns observed in ankle biomechanics. Besides, we studied the transitions from level walking to stair ascent and from stair descent to level walking and showed that mechanical elements can be used to model these transitions as well. These results are promising to the design of next generation ankle orthotic and prosthetic systems because they show that relatively simple mechanical elements can be utilized to mimic ankle biomechanics. PMID- 17271243 TI - Development of practical and effective hybrid exercise for use in weightless environment. AB - Bedrest and spaceflight are associated with profound losses of muscle bulk and strength which hinder patient's or astronaut's health and reintegration into daily life. We attempted to do two things in this small pilot study. First, we assessed the potential of hybrid electrical stimulation-volitional contraction exercise program to increase proximal lower extremity strength, muscle bulk, and bone mineral density (BMD). Second, we assessed the utility of unilateral lower limb suspension (ULLS) in producing losses in these quantities comparable to those that occur during bedrest and spaceflight. More specifically, this study made an initial evaluation of (1) ability of hybrid exercise program to preserve knee extensor and flexor maximum volitional contraction (MVC), cross-sectional area (CSA), and BMD in 4 healthy men between ages of 22 and 24, and (2) utility of ULLS in producing decrements in these parameters similar to those that occur in weightless environment in single 38 year-old male. Results show that CSA of rectus femoris and hamstrings increased about 5.3% and femoral BMD by 7%. MVC may have exhibited a more complex behavior with 3.0% at end of training, followed by 9.3% at follow-up. ULLS resulted in dramatic losses of strength (70%), CSA (4.8%), and BMD (8.2%). PMID- 17271244 TI - Two-point discrimination threshold as a function of frequency and polarity at fingertip by electrical stimulation. AB - The effect of frequencies and current polarity of electrical stimulation to fingertip was investigated toward realizing electrocutaneous display. We measured the two-point discrimination threshold of electrical stimulation with 1.0 mm diameter electrodes spaced by 2.0 mm. The waveform pattern with the smallest two point discrimination threshold was anode at frequencies from 200 to 400 Hz; most subjects could clearly discriminate the physical separation of 4 mm, some of them could discriminate 2 mm with optimized electrical stimulation. PMID- 17271245 TI - Progress in the development of a multifunctional hand prosthesis. AB - A new experimental hand prosthesis design is presented that differs from that of conventional prostheses. With the objective of addressing consumers' requirements, functionality was increased and cosmetic appearance became more natural. By integrating a hydraulic system with 8 small fluidic actuators at the digit joints, different important grasping patterns of everyday life can be performed. These are: power grasp, hook grasp, precision grasp, lateral pinch, and a posture to operate a keyboard with the extended index. As a result of multi articulation and the inherent compliancy of the actuators, objects can be grasped adaptively. Moreover, a vibrotactile feedback system makes the prosthesis controllable without visual attention. For a more natural appearance, the hand is covered by a cosmetic silicone rubber glove. The hands are designed for performing activities of everyday life, including office work. The new hand design can help closing the gap between purely cosmetic hands and functional hands. PMID- 17271246 TI - Modified Weiss's equation for strength-duration curve in magnetic stimulation. AB - There is increasing interest in the use of magnetic stimulation as a modality for clinical examination and therapy. It is desirable that the eddy current density produced by a change in the strength of a magnetic field should be greater than the excitability threshold of the muscles or nerves to be stimulated. The eddy current waveform differs from rectangular current waveform common in electrical applications. Little basic study has been done on the effects of magnetic stimulation on threshold values, chronaxies and other aspects of the eddy current waveforms. In this paper, the authors have attempted to measure the strength duration curve (S-D curve) of eddy currents on the sural muscle of the bullfrog and have proposed a new S-D curve formula for eddy currents in place of Weiss's equation for rectangular current waveforms. PMID- 17271247 TI - Artificial stimulation of the peripheral nerves to generate natural-like activity in the central nervous system. AB - In the present work we study how sensory inputs conveyed by nerve fibers in the form of spatiotemporal patterns generate different responses in the central nervous system (CNS) depending on the physical characteristics of the stimulus applied and then we reproduce similar responses by means of electrical stimulation of the nervous fibers. PMID- 17271248 TI - A laboratory testing and driving system for AIROF microelectrodes. AB - The charge-injection currents of AIROF (activated iridium oxide film) microelectrodes, which are subjected to charge-balanced biphasic pulsing or monophasic current pulsing, have to be limited such that the anodic and cathodic voltage excursions are kept within safe limits of operation. In earlier studies it has been shown that when using anodic bias asymmetry in the magnitude of the balanced biphasic waveform can be used to increase the charge injection capacity of AIROF electrodes. We present the design of a single-channel testing and driving system for laboratory testing and driving of AIROF microelectrodes within safe charge-injection limits. PMID- 17271249 TI - Activation patterns of the tongue muscles with selective stimulation of the hypoglossal nerve. AB - The upper airways were imaged in anesthetized beagles to investigate the effect of selective stimulation of the hypoglossal nerve (HG) with a multi-contact peripheral nerve electrode. A fiberscope lead (diam. 5 mm) was inserted through the proximal end of the tracheostomy and fixed at 1 cm behind the uvula to image the oro- and nasopharynx while the head was fixed at either 30 degrees or 60 degrees from the horizontal with the mouth open or closed. Images of the tongue were recorded with a camera in open mouth positions. These images show that stimulations delivered through the electrode contacts placed around the HG nerve trunk can generate several different activation patterns of the tongue muscles. Some of these patterns translate into a substantial increase in the pharyngeal opening size while some others decrease it. The activation patterns vary as a function of the head position and the lower jaw. These results suggest that selective stimulation of the HG nerve can be a useful technique to maximize the effects of HG nerve stimulation in removing the obstructions in sleep apnea patients. PMID- 17271250 TI - Implantable biaxial piezoresistive accelerometer for sensorimotor control. AB - This paper describes the design, fabrication and test results of a novel biaxial piezoresistive accelerometer and its incorporation into a miniature neuromuscular stimulator called a BION. Because of its highly symmetric twin mass structure, the X and Z axis acceleration can be measured at the same time and the cross axis sensitivity can be minimized by proper piezoresistor design. The X and Z axis sensitivities of the biaxial accelerometer are 0.10 mV/g/V and 1.40 mV/g/V, respectively, which are further increased to 0.65 mV/g/V and 2.40 mV/g/V, respectively, with extra silicon mass added to the proof mass. The cross-axis sensitivity is less than 3.3% among X, Y and Z-axis. An orientation tracking method for human segments by measuring every joint angle is also discussed in this paper. Joint angles can be obtained by processing the outputs of a pair of biaxial accelerometers (placed very close to the joint axis on the adjacent limb links), without having to integrate acceleration or velocity signals, thereby avoiding errors due to offsets and drift. PMID- 17271251 TI - Battery powered BION FES network. AB - The Alfred Mann Foundation is completing development of a coordinated network of BION microstimulator/sensor (hereinafter implant) that has broad stimulating, sensing and communication capabilities. The network consists of a master control unit (MCU) in communication with a group of BION implants. Each implant is powered by a custom lithium-ion rechargeable 10 mW-hr battery. The charging, discharging, safety, stimulating, sensing, and communication circuits are designed to be highly efficient to minimize energy use and maximize battery life and time between charges. The stimulator can be programmed to deliver pulses in any value in the following range: 5 microA to 20 mA in 3.3% constant current steps, 7 micros to 2000 micros in 7 micros pulse width steps, and 1 to 4000 Hz in frequency. The preamp voltage sensor covers the range 10 microV to 1.0 V with bandpass filtering and several forms of data analysis. The implant also contains sensors that can read out pressure, temperature, DC magnetic field, and distance (via a low frequency magnetic field) up to 20 cm between any two BION implants. The MCU contains a microprocessor, user interface, two-way communication system, and a rechargeable battery. The MCU can command and interrogate in excess of 800 BlON implants every 10 ms, i.e., 100 times a second. PMID- 17271252 TI - First subject evaluated with simulated BION treatment in genioglossus to prevent obstructive sleep apnea. AB - We are using percutaneous electrical stimulation to simulate BION activation of posterior genioglossus during sleep to prevent occurrences of obstructive sleep apnea (OSA). Patients with OSA due to tongue prolapse are recruited in this ongoing clinical study for an overnight session in a sleep laboratory. Bipolar hooked wires are inserted percutaneously into the tongue muscle, from under the chin at midline, and used for neuromuscular stimulation. Data are collected with polysomnography and analyzed to compare the efficacy of proposed treatment to conventional CPAP or the untreated state. Encouraging preliminary results from the first study participant are described. PMID- 17271253 TI - Sensing human arm posture with implantable sensors. AB - In order to achieve functionally useful movement, sensory information is required for control of neuromuscular activation. This paper describes implantable sensor modalities to replace normal proprioceptors in feedback control. They can be packaged into miniature, wireless neural stimulators called BIONs. Sensing techniques and strategies for analyzing and combining various sensor signals are presented. These sensors include a DC accelerometer and RF magnetic sensor. Several sensor system configurations are proposed to accommodate different clinical requirements and real-time measurement of the position and orientation of human arms. PMID- 17271254 TI - In vitro and in vivo testing of a wireless multichannel stimulating telemetry microsystem. AB - An inductively powered 64-site current microstimulating system, Interestim-2B, with a modular architecture and minimal number of off-chip components has been developed for neural prosthesis applications. Interestim-2B can generate any arbitrary current waveform and supports a variety of monopolar and bipolar stimulation protocols. A common analog line provides access to each site potential, and exhausts residual stimulus charges. In situ site impedance measurement capability helps indicate the defective sites in chronic stimulations. This paper also summarizes some of the in vitro and in vivo experimental results using a 16-site implant. PMID- 17271255 TI - Improving mechanical stiffness of coated benzocyclobutene (BCB) based neural implant. AB - We briefly report recent results of a simple alternate method to improve mechanical stiffness of BCB polymer neural implant for surgical insertion into brain tissue, which uses coatings dissolvable in bio-fluids. We have studied three different coating materials such as thermo-reversible gel Poloxamer 407, glucose (C6H12O6) and regular table sugar that were applied by dip coating onto the implant surface. The preliminary results of this study have shown that coating BCB probes with Poloxamer 407 polymer, a thermo-reversible gel, or table sugar significantly improves the buckling strength. However, the table sugar coating provides the greatest increase in stiffness, which is sufficient to penetrate both the preserved and live brain tissues without buckling. PMID- 17271256 TI - Development of communication supporting device controlled by eye movements and voluntary eye blink. AB - A communication interface controlled by eye movements and voluntary eye blink has been developed for disabled individuals who have motor paralysis and therefore cannot speak. Horizontal and vertical electro-oculograms were measured using two surface electrodes referring to an earlobe electrode. Four directional cursor movements and one selection were realized by logically combining the detected two channel signals. Virtual input experiments were conducted on a virtual screen keyboard. Its usability and accuracy were improved using our proposed method. PMID- 17271257 TI - Preliminary study of neurite outgrowth within polyimide microtubes. AB - The cone electrode first developed by P.R. Kennedy paved headway in the area of cortical prostheses. While effective, to date, no optimization of the materials, length, diameter or controlling neurotrophic effects have been extensively quantified for such systems. This paper describes an in-vitro model system for the study of neurite outgrowth using PC-12 cells and an array of polyimide microtubes. Our aim is to obtain preliminary design specifications for the eventual optimization of in-vivo neurotrophic electrodes. We performed preliminary characterization of the number and average lengths of PC-12 neurites that penetrated into the tubes mounted within a standard Petri dish. To describe system performance, we observed an increase in the average number of neurites that grew into the tubes over a period of days. We also observed an increase in the average length of the neurites (with a 95% confidence) between day 3 and day 4 of between 14.97 microm and 62.27 microm. In addition, we measured a length change (with a 95% confidence) between day 4 and day 6 of 93.51 microm and 145.45 microm. These results will soon be augmented by quantification of neurites using a photo lithographically patterned glass microgroove system. PMID- 17271258 TI - The recording properties of a multi-contact nerve electrode as predicted by a finite element model of the canine hypoglossal nerve. AB - Most functional electrical stimulation (FES) systems rely only on unidirectional (i.e., efferent) activation of the target organ to yield therapeutic outcomes. For applications involving multi-fasciculated nerves, however, artificial sensors have exhibited limited results. As such, the flat-interface-nerve-electrode (FINE) is presented as a means of obtaining an effective closed-loop control system. To investigate the ability of this electrode to achieve selective recordings at physiological signal-to-noise ratio (SNR), a finite element model (JFEM) of a beagle hypoglossal nerve with an implanted FINE was constructed. Action potentials (AP) were generated at various SNR levels and the performance of the electrode was assessed with a selectivity index (0 < or = SI < or = 1; ability of the electrode to distinguish two active sources). Computer simulations yielded a selective range (0.05 < or = SI < or = 0.76) that was (1) related to the inter-fiber distance and (2) used to predict the minimum inter-fiber distance (0.23 mm < or = d < or = 1.42 mm) required for selective recording. The results of this study suggest that the FINE can record neural activity from a multi fasciculated nerve and, more importantly, distinguish neural activity from pairs of fascicles at physiologic SNR. PMID- 17271259 TI - Area saving stimulator cells for multielectrode arrays featuring adaptive waveform generation and monitoring. AB - A new area saving stimulator cell is described, which is suitable for implantable microstimulators with large numbers of electrodes. The cell generates biphasic charge balanced voltage waveforms by continuous monitoring of the microelectrode voltage during the cathodic and anodic phases. The stimulator provides high voltage compliance and is intended for use with indium oxide micro electrodes with a limited electrochemical potential window. Thus, the new approach can improve electrode count, microelectrode reliability, stimulation efficiency, and power supply longevity. It saves chip area, since large w/l transistors or large capacitors are not required for a CMOS integration of the stimulator cell. The system can be easily extended for action potential recording. PMID- 17271260 TI - A sieve electrode as a potential autonomic neural interface for bionic medicine. AB - We examined the applicability of a sieve electrode to the autonomic nervous system as a potential neural interface for bionic medicine. We developed, using a Si-semiconductor process, a sieve electrode having a square diaphragm (1 mm in one side, 12 microm in thickness) with 30-81 penetrating square holes (50-100 microm in one side). In the first protocol, we implanted the sieve electrode to the vagal nerve in rats. One hundred and twenty days after the implantation, cuff electrodes were attached to the vagal nerve proximal and distal to the sieve electrode under halothane anesthesia. The evoked action potential was recorded from the sieve electrode by nerve stimulation via the cuff electrodes. The evoked action potential was also recorded from the cuff electrodes by nerve stimulation via the sieve electrode. In the second protocol, we implanted the sieve electrode to the renal sympathetic nerve in rabbits. Forty days after the implantation, the spontaneous action potential or sympathetic nerve activity was recorded under pentobarbital anesthesia. In conclusion, we were able to record the evoked and spontaneous action potentials using the sieve electrode. The sieve electrode will provide a useful neural interface for recording and stimulating the autonomic nervous system. PMID- 17271262 TI - Benzocyclobutene (BCB) based neural implants with microfluidic channel. AB - Benzocyclobutene (BCB) based intracortical neural implants for basic neuroscience research in animal models was fabricated, in which microfluidic channel was embedded to deliver chemical reagents. BCB presents several attractive features for chronic applications: flexibility, biocompatibility, desirable chemical and electrical properties, and can be easily manufactured using existing batch microfabrication technology; The fabricated implants have single shank with three recording sites (20 x 20 microm) and two reservoirs (inlet and outlet). The channel had large volume (40 microm width and 10 microm height), and hydrophobic surface to provide a high degree of chemical inertness. All the recording sites were positioned near the end of the shank in order to increase the probability of recording neural signals from a target volume of tissue. In vitro biocompatibility tests of fabricated implants revealed no adverse toxic effects on cultured cells. The implant with a 5 microm silicon backbone layer penetrated rat's pia without buckling, a major drawback of polymer alone. The averaged impedance value at 1 kHz was approximately 1.2 MOmega. Water flowing through the channel was observed. Depending on the amount of the driving pressure from the syringes, the delivery speed of the water was totally controlled. PMID- 17271261 TI - Flexible and extendible neural stimulation/recording device based on cooperative multi-chip CMOS LSI architecture. AB - An LSI-based cooperative multi-chip neural stimulation/recording device is proposed and fabricated. The proposed multi-chip device consists of small (600 microm x 600 microm in the present design) intelligent neural stimulation/recording chips (unit chip). The unit chip has a neural stimulation/recording electrode array and individual control circuit. It can work with other unit chips cooperatively. One can configure any number of the unit chips as the multi-chip neural stimulation/recording device. Compared to conventional single-chip architecture, the proposed multi-chip architecture has advantages in thinness, mechanical strength and flexibility, and extendibility. That makes the multi-chip neural stimulation/ recording device more suitable for in vivo applications than conventional single-chip devices. Packaging technology for cooperative multi-chip device is also discussed. We developed a thin, flexible packaging technique for the multi-chip neural stimulation/recording device and LSI-compatible Pt/Au stacked biocompatible bump electrode. PMID- 17271263 TI - A TinyOS-based wireless neural interface. AB - The overlay of a neural interface upon a TinyOS-based sensing and communication platform is described. The system amplifies, digitally encodes, and transmits two EEG channels of neural signals from an un-tethered subject to a remote gateway, which routes the signals to a client PC. This work demonstrates the viability of the TinyOS-based sensor technology as a foundation for chronic remote biological monitoring applications, and thus provides an opportunity to create a system that can leverage from the frequent networking and communications advancements being made by the global TinyOS-development community. PMID- 17271264 TI - Hybrid RF/IR transcutaneous telemetry for power and high-bandwidth data. AB - As neuroprosthetic control systems continue to advance and increase in channel density, there will be a constant need to deliver data at higher bandwidths in and out of the body. Currently, RF telemetry and inductive coupling are the most commonly used methods for transmitting power and electronic data between implants and external systems, and state of the art systems can deliver data rates up to hundreds of kilobits per second. However, it is difficult to operate implanted medical RF links at higher data rates due to electromagnetic compatibility (EMC) constraints. In this study, we investigate the potential for hybrid telemetry systems that use constant-frequency RF inductive links for power and transcutaneous infrared (IR) signals for data. We show that with commercially available infrared communication components, data rates of up to 40 Mbits per second can be transmitted out across 5 mm of skin with an internal device power dissipation under 100 mW. PMID- 17271265 TI - High-yield benzocyclobutene(BCB) based neural implants for simultaneous intra- and extracortical recording in rats. AB - A unique structure for chronically implantable cortical electrodes based on benzocyclobutene (BCB) biopolymer was designed to perform intracortical and extracortical neural recording simultaneously in basic neuroscience research using animal models. It was fabricated on silicon wafer using standard planar CMOS surface microfabrication technique. Dry-etchable BCB was used to insulate the electrode and provide flexibility for micro-motion compliance between brain tissue and skull. This electrode is also designed to ease the handling and implantation during the surgery and to integrate buffer circuits to improve the signal-to-noise ratio. The reliable fabrication process was developed to improve the electrode yield and performance. A 15 microm thick tungsten layer was sandwiched in the electrode tip to improve the stiffness for easy insertion during the surgery. The fabricated electrodes have two intra-cortical recording sites (20 x 20 microm) in the tip penetrating into the cortex and two epidural recording sites (80 x 80 microm) on each side wing, providing a 6 channel system. One via (40 x 40 microm) was also incorporated in the tip to balance the tip and provide the bio-seeding to improve the implants and neural tissue interaction. The acute surgical testing suggests that this electrode structure can penetrate the pia into the cortical tissue without damaging the electrode. PMID- 17271266 TI - Design methods for innovative hand prostheses. AB - This paper presents the design methods followed in order to overcome the limits of the current prosthetic hands. The prosthesis biomechatronic approach arises from the knowledge of the biological system, assumed validated by its natural evolution. Nevertheless, the state of the art of technology, actuators, sensors, electronics and software, forces some trade-off in the implementation of the prototypes. The current hand prototype constitutes the platform used to direct all efforts of the prosthesis designer to the final goal: the cybernetic hand directly connected to the nervous system. PMID- 17271267 TI - Impedance characterization of microarray recording electrodes in vitro. AB - The mechanisms underlying performance degradation of electrodes chronically implanted in the central nervous system (CNS) remain unclear. Several components of the normal brain wound healing response were evaluated to determine if their presence correlates with increased electrical impedance that may be a factor in loss of device performance. Microelectrode recording arrays were electrically characterized in vitro in the presence of saline, culture media with 10% fetal bovine serum (FBS), and various CNS cell types isolated from Sprague-Dawley rats and cultured in media with 10% FBS. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were performed using a three-electrode system. Potential cycling during CV caused an immediate decrease in electrical impedance, which increased with time toward the pre-cycling value, with the effect of cycling remaining significant for several days. The addition of serum caused a significant but not substantial increase in impedance. The inclusion of various cell types known to participate in the brain wound healing response caused a significant increase in impedance immediately after seeding on the order of 50%, and this value increased or remained constant for up to several weeks. It is unclear whether the magnitude of increased impedance is sufficient to account for loss of device performance. PMID- 17271268 TI - Varying the time delay of an action potential elicited with a neural-electronic stimulator. AB - There have been various theoretical and experimental studies presented in the literature that focus on interfacing neurons with discrete electronic devices such as transistors. It has also been demonstrated experimentally that neural electronic devices can be used to elicit action potentials in a target neuron in close proximity to the neural-electronic stimulator. The time delay between stimulus and the onset of the neural action potential can be varied by varying the pulse amplitude and width generated by the neural-electronic stimulator (transistor). PMID- 17271269 TI - Motor imagery classification by means of source analysis methods. AB - We report our investigation of classification of imagined left and right hand movements by applying source analysis methods. Independent component analysis (ICA) is used as a spatio-temporal filter, then equivalent dipole analysis and cortical current density imaging methods are applied to reconstruct equivalent sources, to aid classification of motor imagery tasks in a human subject. The classification was considered correct if the equivalent source was found over the motor cortex in the corresponding hemisphere. A classification rate of about 80% was achieved in the human subject studied using both the equivalent dipole analysis and the cortical current density imaging analysis. PMID- 17271270 TI - Classification of motor imagery EEG patterns and their topographic representation. AB - We have developed a single trial motor imagery (MI) classification strategy for the brain computer interface (BCI) applications by using time-frequency synthesis approach to accommodate the individual difference, and using the spatial patterns derived from EEG rhythmic components as the feature description. The EEGs are decomposed into a series of frequency bands, and the instantaneous power is represented by the envelop of oscillatory activity, which formed the spatial patterns for a given electrode montage at a time-frequency grid. Time-frequency weights determined by training process were used to synthesize the contributions at the time-frequency domains. The overall classification accuracies for three selected human subjects performing left or right hand movement imagery tasks, were about 87 percent in the ten-fold cross validation without rejecting trials. The loci of motor imagery activity were shown in the spatial topography of differential mode patterns over the sensorimotor area. The present method promises to provide a useful alternative as a general purpose classification procedure for motor imagery classification. PMID- 17271271 TI - Generalizing to new subjects in brain-computer interfacing. AB - This paper evaluates an algorithm based on support vector machines to analyze EEG data from the P300 speller brain-computer interface paradigm. We evaluated the performance of this technique on own experimental data from 8 subjects and achieved high transfer rates of up to 97.57 bits/min (mean 47.26 bits/min) within subjects. We then investigated how well the classifier generalizes when it is trained on data from a set of several subjects and then applied on data from a new subject to use this BCI in a pretrained fashion. Transfer rates up to 61.04 bits/min were achieved (mean 17.64 bits/min) for this situation indicating an encouraging generalization performance. PMID- 17271272 TI - Co-adaptive Kalman filtering in a naive rat cortical control task. AB - Control of prosthetic devices is possible via extra-cellular recordings from cortical neurons. Many of the current cortical control paradigms consist of analyzing the relationship between cortical activity and measured arm movements, and then using this known relationship to map cortical activity to similar prosthetic arm movements. However, measured arm movements are not feasible for amputees or patients with mobility limitations hindering their ability to perform such movements. Here we explore an alternative approach using a rat model in which subjects learn prosthesis control via an adaptive decoding filter that adjusts to the modulation patterns recorded from neurons in the motor cortex. Our methodology takes into account the ability of a subject to learn an effective response strategy in conjunction with online filter adaptation. A modified Kalman filter is demonstrated to "co-adapt" by training on past periods of significant modulation during expected prosthetic device movement. Feedback pertinent to completing the cortical task is given to aid the animal in adopting a response strategy maximizing reward. One subject was able to perform the task consistently above chance after 2 days (4 sessions) of training. PMID- 17271273 TI - Extracting features for a brain-computer interface by self-organising fuzzy neural network-based time series prediction. AB - This paper presents a novel feature extraction procedure (FEP) for extracting features from the electroencephalogram (EEG) recorded from subjects producing right and left motor imagery. Four self-organizing fuzzy neural networks (SOFNNs) are coalesced to perform one-step-ahead predictions for the EEG time series data. Features are derived from the mean squared error (MSE) in prediction or the mean squared of the predicted signals (MSY). Classification is performed using linear discriminant analysis (LDA). This novel FEP is tested on three subjects offline and classification accuracy (CA) rates approach 94% with information transfer (IT) rates >10 bits/min. Minimum subject specific data analysis is required and the approach shows good potential for online feature extraction and autonomous system adaptation. PMID- 17271274 TI - Brain computer interface: estimation of cortical activity from non invasive high resolution EEG recordings. AB - The aim of this paper is to analyze whether the use of the cortical activity estimated from non invasive EEG recordings could be useful to detect mental states related to the imagination of limb movements. Estimation of cortical activity was performed on high resolution EEG data related to the imagination of limb movements gathered in five normal healthy subjects by using realistic head models. Cortical activity was estimated in region of interest associated with the subject's Brodmann areas by using depth-weighted minimum norm solutions. Comparisons between surface recorded EEG and the estimated cortical activity were performed. The estimated cortical activity related to the mental imagery of limbs in the five subjects is located mainly over the contralateral primary motor area. The unbalance between brain activity estimated in contralateral and ipsilateral motor cortical areas relative to the finger movement imagination is greater than those obtained in the scalp EEG recordings. Results suggest that the use of the estimated cortical activity for the motor imagery of upper limbs could be potentially superior with respect to the use of surface EEG recordings. This is due to a greater statistically significant unbalance between the activity estimated in the contralateral and ipsilateral hemisphere with respect to those observed with surface EEG. These results are useful in the context of the development of a non invasive brain computer interface. PMID- 17271275 TI - 1(st) order class separability using EEG-based features for classification of wrist movements with direction selectivity. AB - 28 channel EEG data were recorded while a subject performed wrist movements in four directions. Four feature types were extracted for each channel following optimized filtering of the signals. The potential performance of each feature and channel for use in the classification of the EEG signals was analyzed by estimating the relative class overlap using a first order histogram approach. The best feature/channel configurations contained channels both that were close and far from motor areas. While the scope and depth of the study was very limited, the results do suggest more attention should be paid to non-motor areas when investigating movement related EEG. PMID- 17271276 TI - An extensible infrastructure for fully automated spike sorting during online experiments. AB - When recording extracellular neural activity, it is often necessary to distinguish action potentials arising from distinct cells near the electrode tip, a process commonly referred to as "spike sorting." In a number of experiments, notably those that involve direct neuroprosthetic control of an effector, this cell-by-cell classification of the incoming signal must be achieved in real time. Several commercial offerings are available for this task, but all of these require some manual supervision per electrode, making each scheme cumbersome with large electrode counts. We present a new infrastructure that leverages existing unsupervised algorithms to sort and subsequently implement the resulting signal classification rules for each electrode using a commercially available Cerebus neural signal processor. We demonstrate an implementation of this infrastructure to classify signals from a cortical electrode array, using a probabilistic clustering algorithm (described elsewhere). The data were collected from a rhesus monkey performing a delayed center-out reach task. We used both sorted and unsorted (thresholded) action potentials from an array implanted in pre-motor cortex to "predict" the reach target, a common decoding operation in neuroprosthetic research. The use of sorted spikes led to an improvement in decoding accuracy of between 3.6 and 6.4%. PMID- 17271277 TI - Effect of ocular artifact removal in brain computer interface accuracy. AB - We report the effect of removing ocular artifacts on the performance of a word processing application based on the event related potential P300. Various methods of removing artifacts have been reported. The efficiency of these algorithms are usually done by subjective visual comparisons. Noting that there is a direct correlation of artifact rectifying algorithms to the accuracy in a brain computer interface system's accuracy, we present this work as a means to compare different algorithms. PMID- 17271278 TI - Multi-stream HMM for EMG-based speech recognition. AB - A technique for improving the recognition accuracy of EMG-based speech recognition by applying existing speech recognition technologies is proposed. The authors have proposed an EMG-based speech recognition system that requires only mouth movements, voice need not be generated. A multi-stream HMM (hidden Markov model) and feature extraction technique are applied to EMG-based speech recognition. 3 channel facial EMG signals are collected from ten subjects when uttering 10 Japanese isolated digits. One channel corresponds to one stream. By examining various features, we found that the delta component of the static parameter leads to higher accuracy. Compared to equal stream weighting, the individual optimization of stream weights increased recognition accuracy by 4.0% which corresponds to a 12.8% reduction in error rate. This result shows that multistream HMM is effective for the classification of EMG. PMID- 17271279 TI - Reduced spatially correlated noise influence using subspace source localization method FINES. AB - We have developed a high resolution subspace approach for EEG source localization within a realistic geometry inhomogeneous head model. The present study aims to reduce the influence caused by spatially correlated noise from background activities using FINES. Computer simulations were conducted on the realistic geometry head volume conductor model and compared with the classic MUSIC algorithm. The FINES approach was also applied to source localization of motor potentials induced by the execution of finger movement in a human subject. The present results suggest that FINES is insensitive to spatially correlated noise, and has enhanced performance as compared with MUSIC. PMID- 17271280 TI - Background activity originating from same area as events in the EEG of paediatric patients with focal epilepsy. AB - The aim of this study was to investigate the presence of apparent non epileptiform activity arising in the same brain area as epileptiform activity in the EEG of paediatric patients with focal epilepsy. The EEG from eight patients was analyzed by an automated method which detects epochs with a single underlying source having a dipolar potential distribution. The EEG with the highlighted detections was then rated by an EEGer with respect to epileptiform activity. Although EEGer-marked events and computer detections often coincided, in five out of the eight patients a substantial number of other detections were found to arise from the same area as the marked events. The morphology of a high proportion of these other detections did not resemble typical epileptiform activity. PMID- 17271281 TI - EEG-MEG source characterization in post surgical epilepsy: the influence of large cerebrospinal fluid compartments. AB - A study on the effect of including a large post-surgical cavity filled with cerebrospinal fluid (CSF) in the modeling of EEG-MEG in epilepsy was performed. Real, simultaneous EEG-MEG data and volume conductor models constructed on the basis of 3DT1 MRI data of the same patient were used. Results show that for MEG and EEG source localization errors remain limited to 0.5 cm, but source strengths found are more consistent when CSF is included. Also the localization differences between EEG and MEG are smaller and the fit to MEG data is substantially better. PMID- 17271282 TI - Time-varying cortical connectivity by high resolution EEG and directed transfer function: simulations and application to finger tapping data. AB - The problem of the definition and evaluation of brain connectivity has become a central one in neuroscience during the latest years, as a way to understand the organization and interaction of cortical areas during the execution of cognitive or motor tasks. The method of the directed transfer function (DTF) is a frequency domain approach to this problem, based on a multivariate autoregressive modeling of time series and on the concept of Granger causality. So far, all the connectivity estimations performed on cerebral electromagnetic signals were computed between signals gathered from the electric or magnetic sensors. However, the spreading of the potential from the cortex to the sensors makes it difficult to infer the relation between the spatial patterns on the sensor space and those on the cortical sites. In this paper we propose the use of the DTF method on cortical signals estimated from high resolution EEG recordings, which exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. As main contributions of this work, we present the results of a wide simulation study, aiming to evaluate performances of DTF application on this kind of data, and a statistical analysis (via the ANOVA, analysis of variance) of the results obtained for different levels of signal to noise ratio and temporal length, as they have been systematically imposed on simulated signals. Finally, we provide an application to the estimation of cortical connectivity from high resolution EEG recordings related to finger tapping movements. PMID- 17271283 TI - Study on the spatial resolution of EEG--effect of electrode density and measurement noise. AB - The spatial resolution of electroencephalography (EEG) is studied by means of inverse cortical EEG solution. Special attention is paid to the effect of electrode density and the effect of measurement noise on the spatial resolution. A three-layer spherical head model is used as a volume conductor to obtain the source-field relationship of cortical potentials and scalp potential field. Effect of measurement noise is evaluated with truncated singular value decomposition (TSVD). Also simulations about different electrode systems' ability to separate cortical sources are performed. The results show that as the measurement noise increases the advantage of dense electrode systems decreases. Our results suggest that in clinical measurement environment it is always beneficial to use at least 64 measurement electrodes. In low-noise realistic measurement environment the use of even 256 measurement electrodes is beneficial. PMID- 17271284 TI - Non-linearities in the blood-oxygenation-level dependent (BOLD) response measured by functional magnetic resonance imaging (fMRI). AB - A central question in the analysis of functional magnetic resonance imaging (IMRI) data is whether the measured fMRI signal summates in a linear fashion over repeated inputs. Most fMRI studies collect images sensitive to blood-oxygenation level dependent (BOLD) contrast, which measures the local amount of deoxygenated hemoglobin (dHb). When neurons are active, more oxygenated hemoglobin is supplied than is needed for their metabolic demands, resulting in a decrease in dHb and an increase in MR signal. For analysis of fMRI data, researchers must therefore create experimental hypotheses of the measurable BOLD response based upon the predicted neuronal activity. An influential early model of the fMRI BOLD response assumes that BOLD activity is a linear transformation of neuronal input, representing the filtering effects of the vascular system. Recent studies have called this interpretation into question, due to observed differences in the pattern of linearity across brain regions that serve distinct functions. PMID- 17271285 TI - FMRI signal source analysis using diffusion-weighted spiral-in acquisition. AB - Despite the tremendous growth in functional magnetic resonance imaging (fMRI), susceptibility induced static field inhomogeneity at air/tissue interface have limited the study of ventral brain regions engaged in object recognition and other processes. Furthermore, the spatial extent of fMRI activations in this region may be obscured by contribution of large vessels distant from the precipitating neural events. In this report, a diffusion weighted spiral-in image acquisition was employed to recover fMRI signal in the ventral brain during object recognition with high temporal resolution, as well as to suppress large vessel contributions. The combined methodology of the ventral signal recovery and vascular signal reduction can thus be advantageous for fMRI investigations at the statically inhomogeneous areas. PMID- 17271286 TI - Analysis of brain white matter via fiber tract modeling. AB - White matter fiber bundles of the human brain form a spatial pattern defined by the anatomical and functional architecture. Tractography applied to the tensor field in diffusion tensor imaging (DTI) results in sets of streamlines which can be associated with major fiber tracts. Comparison of fiber tract properties across subjects needs comparison at corresponding anatomical locations. Moreover, clinical analysis studying fiber tract disruption and integrity requires analysis along tracts and within cross-sections, which is hard to accomplish by conventional region of interest and voxel-based analysis. We propose a new framework for MR DTI analysis that includes tractography, fiber clustering, alignment via local shape parametrization and diffusion analysis across and along tracts. Feasibility is shown with the uncinate fasciculus and the cortico-spinal tracts. The extended set of features including fiber tract geometry and diffusion properties might lead to an improved understanding of diffusion properties and its association to normal/abnormal brain development. PMID- 17271287 TI - Quantification of morphological changes in the spinal cord in chronic spinal cord injury using magnetic resonance imaging. AB - Following spinal cord injury (SCI), morphological changes in the spinal cord are observed at the clinically diagnosed level of injury, as well as at segmental levels above and below the injury site due to axonal degeneration. In order to quantify the extent of morphological changes, a three dimensional segmentation of the spinal cord was constructed using magnetic resonance images (MRI) of the cervical spinal cord. Six neurologically intact (NI) and five spinal cord injured (SCI) subjects were scanned using an axial, T2 weighted fluid-attenuated inversion recovery (FLAIR) sequence. The boundaries of the spinal cord volume were then identified using a three-dimensional, seeded region growing technique. The area of 4 slices approximating the C3 segment were measured and the mean area was calculated for each subject. In NI subjects the mean C3 cord area was 75.2 +/ 11 mm(2). In contrast, SC subjects had a mean C3 cord area of 60.4 +/- 7.3 mm(2). This 20% decrease in area for the SCI subjects, compared to the NI subjects, was statistically significant (t-test, p<0.05). These results show that the narrowing of the spinal cord after SCI is measurable using MRI. PMID- 17271288 TI - Analyses of rotational singularities in ferret visual cortex. AB - Activity maps of spatial orientation, obtained by intrinsic optical imaging of the mammalian visual cortex, show the formation of pinwheel-like structures that rotate either clockwise or counterclockwise around zero dimensional points called singularities. Any research that is oriented towards exploring the formation and physiological role of these singularities during an experiment requires an automated tool that can rapidly identify the location of these singularities. In this work we have developed such a tool that looks for the existence of singularities for a certain radius at every pixel location in the angle map. Using data from eleven ferrets, the number of singularities identified was a function of the search radius (0.03325, 0.04665, 0.05985, 0.07315, 0.08645, 0.09975, 0.11305, and 0.12635 mm) and level of image smoothing used. For a given smoothing value, the number of singularities decreased with increasing radius. But the rate of decrease was greater with less smoothing. The more the original image was smoothed, the fewer singularities were identified at a given radius. The trade off between search radius and image smoothing can be partially attributed to spatial sampling resolution. PMID- 17271289 TI - An EEG forward solution using second-order anisotropic FEM. AB - A 2(nd) order finite element method (FEM) algorithm has been developed to solve the anisotropic electroencephalogram (EEG) forward problem and has been evaluated by comparing with analytic solutions in a multispheres concentric head model. The present simulation study indicates that the 2(nd) order FEM provides substantially enhanced numerical accuracy and computational efficiency, as compared with the 1(st) order FEM for comparable numbers of tetrahedron elements. PMID- 17271290 TI - Spatio-temporal EEG dipole estimation by means of a hybrid genetic algorithm. AB - EEG source localization can be considered as a nonlinear optimization process. In the present study, a hybrid genetic algorithm (HGA) is introduced, which combines genetic and local search strategies to overcome the disadvantages of conventional genetic algorithm and local optimization methods. This HGA algorithm was used to localize two dipoles from scalp EEG, and yielded localization accuracy range of 0.95 cm-1.55 cm when the noise level is within 15%, which is better than the Simplex and GA algorithms in localizing multiple dipoles. PMID- 17271291 TI - On the measurement of conductivity distribution of the human head using magnetic resonance electrical impedance tomography. AB - We have applied the magnetic resonance electrical impedance imaging (MREIT) technique to image the three-dimensional (3D) conductivity distribution of the human head. Computer simulations were carried out on a tradition four-sphere head model to test the feasibility of imaging conductivity distribution of the human head. The present results show that the 3D head conductivity distribution could be well reconstructed using MREIT. PMID- 17271292 TI - Event-related brain potentials during visual sentence reading and picture recognition memory tasks. AB - It is uncertain if different brain areas in response to pre-semantic picture processing are functionally homogeneous. Using event-related potentials (ERPs), we aimed to explore the neural activities in different brain regions in relation to processing of sentence memory and picture identification. Healthy subjects were chosen to discriminate visual stimulus pairs, and the ERPs were recorded from the scalp. Two kinds of stimuli were provided for each subject in the present study. One was Chinese sentence reading, referred as task 1. Another one was watching a line-drawing picture to judge if the picture matched the meaning of the sentence before. When the line-drawing picture received by the subject was inconsistent with the meaning of the sentence before, it was called as task 2, otherwise, if incongruous, it was called as task 3. Our findings implicate that stimuli of sentence memory and picture identification may exert neural activities on different working memory areas in the brain of human. PMID- 17271293 TI - Study on effect and mechanism of magnetic fields simulating EEG rhythm upon memory. AB - Magnetic fields simulating EEG rhythm were used to stimulate Wistar rats to explore the effect of magnetic field on retrieval (recall) ability and its mechanism. The results indicated that most of the weak magnetic fields (>10 minutes) simulating the EEG rhythm of human brain impaired the retrieval of long term memory significantly (P<0.05), but weak magnetic field with special rhythm may even have the capability of facilitating memory performance. And the effects of TMS on memory can last for at least several hours (5h) after TMS. Compared with control group, the release of NE, DA and 5-HT in hippocampus of stimulated group increased (P<0.05); While the release of ACh decreased (P<0.05). Through electronic microscope, morphological changes of nerve synapses in hippocampus of rats were observed after weak magnetic stimulation. The percentage of alpha and beta rhythm in EEG power spectra changed in cats after induced by weak magnetic fields simulating the EEG rhythm. PMID- 17271295 TI - EEG source distribution localization using minimum-product and CRESO criteria for Tikhonov regularization. AB - Electroencephalographic (EEG) inverse problems are often ill-posed due to the high condition number of the transfer matrix. In the present work simulated cortical source distributions are reconstructed, using a formulation providing information about extended intracranial distributions, with separate current source and sink positions. To overcome the influence of noise on measured voltages, as expected in real laboratory recordings, the Tikhonov regularization technique (TRT) is used for solving the discrete inverse problem matrix equation. Two criteria are used and compared in providing an approximation to the optimal regularization parameter, the composite residual and smoothing operator (CRESO) criterion and the minimum-product (MP) criterion. For levels of Gaussian measurement noise equal to or greater than 10%, the CRESO criterion performed significantly better than MP criterion, provided that the application of both criteria was extended to include as approximations even boundary regularization parameter values. PMID- 17271294 TI - Examining the influence of the cerebral cortex in range of motion exercise using MEG. AB - In rehabilitating stroke patients, many therapists use range of motion exercise (ROM-ex) at early post onset. There are three general types of ROM-ex: passive, active, and active-assistive ROM-ex is used to prevent joint contracture in paralyzed limbs and to assist in recovery of the central nervous system (CNS). However, its effect on CNS recovery is unclear. Therefore, this study compared the influence of different tasks, including passive and active ROM-ex and imagined extension/flexion at the elbow, on the cerebral cortex. The subjects were six healthy volunteers. We used a magnetoencephalogram (MEG) to measure cerebral cortex activity. In the active ROM-ex task, we confirmed a dipole in the motor area in all subjects. It has been suggested that this dipole is activity of the motor-related field (MRF). By contrast, in the passive ROM-ex experiment, we did not confirm a dipole in the cortex. In addition, in the experiment with no joint motion, in which the subject only imagined moving the elbow joint from flexion to extension, it was possible to estimate a dipole in the motor area. Therefore, an imaginary task might be a possible method of activation when voluntary movement is impossible. PMID- 17271296 TI - Dynamic evaluation of [18F]-FDG uptake in the rat brain by microPET imaging. AB - This study aims to acquire the functional image of the rat brain, small animal positron emission tomography (microPET) with high resolution and sensitivity is adopted to assess the metabolic activity corresponding to the neuronal activity induced by the electrical stimulation of the rat tail using [18F] fluorodeoxyglucose (FDG) as the radiotracer. The microPET imaging technology can provide anatomical and functional information on neuronal activity used to analyze responses in pathway sequence relationships between the thalamus and the cerebral cortex. PMID- 17271297 TI - Spatiotemporal characteristics of MEG and EEG entrainment with photic stimulation in schizophrenia. AB - We examined the periodic synchronous characteristic response to photic stimulation in schizophrenia using electroencephalography (EEG) and magnetoencephalography (MEG). We tested whether neural synchronization deficits were present in subjects with schizophrenia using photic stimulation to evaluate the frequency entrainment in 18 normal subjects and 19 schizophrenia patients. A conventional vertical-type 160-channel MEG (PQ1160C, Yokogawa Electric Corporation) was used. Photic stimulation was at frequencies from 8 to 10.5 Hz at intervals of 0.5 Hz. There were ten stimuli at each frequency, and each lasted 10 seconds. The power spectrum at each site was based on the international 10/20 derivation. The power spectrum in schizophrenia patients was smaller than that in normal subjects at each site. A gender difference was observed in normal subjects, but not in schizophrenia patients. MEG, like EEG, is an effective method for research on neuropathy of the psyche. PMID- 17271298 TI - Studies on cognitive and dynamic brain responses to mono-stimulation in human. AB - Researchers have used primate animals to investigate brain functions at neuron level or even every different level and have achieved a lot progresses and results. However, none of them involved people in their entirety and few studied the dynamics of unfolding brain function as the whole under the life condition of people. Hence people still don't understand well how their cognitive process is completed. We isolated the relatively independent visual system from the complex human body and studied its linkage to cognition. Therefore, by linking stereopsis and cognition this paper studies the cognitive and dynamic response to external mono-stimuli using the electrophysiological method. Investigators directly took part in the entire experimental processes as volunteers. They were able to experience the details of complete cognitive response produced by external stimuli and sense the formation of stable cognition with robustness through personal understanding. The results showed that cognition is a dynamic process of multiple factors. In particular, a new N2 waveform of cognitive characteristics is found to respond to a single stimulus at the advance visual cortex and this N2 waveform is also verified by computing its nonlinear complexity. Differences between dynamic responses to red-blue stereogram pair (RBSGP) and black-white one luminance had response waveforms differed considerably. And the time delay of the peak-to-peak N2 wave in the cognitive dynamic response to the onset of red-blue contrast was greater than the time delay of corresponding N2 peak-to-peak in the response to black-white contrast. Furthermore, our result concurs with the latest advance by A. Anzai in the research of neuron cellular physiology. PMID- 17271299 TI - Imaging and manipulating living neurons with atomic force microscopy. AB - Atomic force microscopy (AFM) applications in medicine and biology promises to be significant. Resolutions of living biological materials provided by this technology in the native environment far surpass any modality currently available. The AFM can also be used to physically interact with the sample of interest, allowing for novel experimentation. This report discusses three dimensional architectures of living chick dorsal root ganglion and sympathetic ganglion somas and growth cones. Secondly, the AFM has been used to inflict damage to these neurons and subsequently image the cell's response to injury. In the Center for Paralysis Research, we intend to expand on these preliminary investigations toward a better understanding of neurotrauma and nerve repair. PMID- 17271300 TI - Hip joint center location by fitting conchoid shape to the acetabular rim region of MR images. AB - This paper proposes a hip joint center (HJC) location method based on the approximating of the acetabulum with a conchoid shape to acetabular rim in MR images. As the human hip joint is not a perfect sphere but it is close to a conchoid shape, the accurate location of the HJC cannot be computed as the center of a sphere. By approximating the acetabulum with a conchoid shape, it is possible to compensate a possible hip joint center location error due to the inaccuracy of 3D surface models for using functional method to calculate HJC location. For the hip joint surgery planning, it is necessary to assess patients' hip range of motions based on the HJC, thus the accurate HJC location is important. PMID- 17271301 TI - Sensorimotor learning and information processing by Bayesian internal models. AB - Fundamental to effective brain-machine interface and neuroprosthesis designs is an understanding of how sensory and motor information are encoded, integrated and adapted by the nervous system. Special session "Neural Information Processing by Bayesian and Internal Models" expounds two current theories of sensorimotor integration which posit that neural information may be encoded centrally as an "internal model" of the environment or as a stochastic state-space model that modulates the activity of spiking neurons. Underlying both theories is a possible role for Bayes' rule--as suggested by the recent findings that the brain may employ Bayesian internal models during certain types of sensorimotor learning in order to optimize task-specific performance and that the emergent activity of certain neural ensembles may be modeled as joint Bayesian point processes. These emerging concepts of neural signal processing have far-reaching implications in applications from rehabilitation engineering to artificial intelligence. PMID- 17271302 TI - A Bayesian decoding algorithm for analysis of information encoding in neural ensembles. AB - Developing optimal strategies for constructing and testing decoding algorithms is an important question in computational neuroscience, In this field, decoding algorithms are mathematical methods that model ensemble neural spiking activity as they dynamically represent a biological signal. We present a recursive decoding algorithm based on a Bayesian point process model of individual neuron spiking activity and a linear stochastic state-space model of the biological signal. We assess the accuracy of the algorithm by computing, along with the decoding error, the true coverage probability of the approximate 0.95 confidence regions for the individual signal estimates. We illustrate the new algorithm by analyzing the position and ensemble neural spiking activity of CA1 hippocampal neurons from a rat foraging in an open circular environment The median decoding error during 10 minutes of open foraging was 5.5 cm, and the true coverage probability for 0.95 confidence regions was 0.75 using 32 neurons. These findings improve significantly on our previous results and suggest an approach to reading dynamically information represented in ensemble neural spiking activity. PMID- 17271303 TI - The nervous system uses internal models to achieve sensory integration. AB - All linear accelerometers measure gravito-inertial force, which is the sum of gravitational force (tilt) and inertial force due to linear acceleration (translation). Neural strategies must exist to elicit tilt and translation responses from this ambiguous cue. To investigate these neural processes, we developed a model of human responses and simulated a number of motion paradigms used to investigate this tilt/translation ambiguity. In this model, the separation of GIF into neural estimates of gravity and linear acceleration is accomplished via an internal model made up of 3 principal components: 1) the influence of rotational cues (e.g., semicircular canals) on the neural representation of gravity, 2) the resolution of gravito-inertial force into neural representations of gravity and linear acceleration, and 3) the neural representation of the dynamics of the semicircular canals. By combining these simple hypotheses within the internal model framework, the model mimics human translation and tilt responses for preliminary data from one human subject. These modeled response characteristics are consistent with preliminary data and with the hypothesis that the nervous system uses internal models to estimate tilt and translation in the presence of ambiguous sensory cues. PMID- 17271304 TI - How are internal models of unstable tasks formed? AB - The results of recent studies suggest that humans can form internal models that they use in a feedforward manner to compensate for both stable and unstable dynamics. To examine how internal models are formed, we performed adaptation experiments in novel dynamics, and measured the endpoint force, trajectory and EMG during learning. Analysis of reflex feedback and change of feedforward commands between consecutive trials suggested a unified model of motor learning, which can coherently unify the learning processes observed in stable and unstable dynamics and reproduce available data on motor learning. To our knowledge, this algorithm, based on the concurrent minimization of (reflex) feedback and muscle activation, is also the first nonlinear adaptive controller able to stabilize unstable dynamics. PMID- 17271305 TI - Change of desired trajectory caused by training in a novel motor task. AB - When the human motor system adapts to novel dynamics of the arm during reaching, hand trajectories tends to converge toward a roughly straight line. This straight line is thought to be the desired trajectory of the system. Trial-to-trial changes in performance are well described by a first order state-space model: errors in a given trial affect performance on the subsequent trial as a function of the distance in state space between the two trials. This function describes the generalization patterns that govern adaptation. Whereas the desired trajectory and the generalization function have been quantified for short-term adaptation, little is known about their behavior with long-term training. We report that when subjects are trained to reach in novel force fields over multiple days, the state-space model suggests that the desired trajectory undergoes systematic changes. In a constant field, the desired trajectory becomes curved. The direction of change of the desired trajectory is affected by the training protocol, such that occasional unperturbed trials (catch trials) caused subject to increasingly under-compensate for the perturbations whereas a lack of such trials caused subjects to increasingly overcompensate for the perturbations. We suggest that the desired trajectory is not constant, but is a result of an optimization that considers the success rate. In this optimization process, subjects weigh more heavily the importance of certain trials: either those that are infrequent or those that cause large errors. PMID- 17271306 TI - Derivation of EEG information from rates of change in order parameter and free energy dissipation. AB - EEG patterns correlated with conditioned stimuli were sought in amplitude modulation of synchronous beta-gamma oscillations (12-80 Hz). EEG signals were recorded from high-density 8 x 8 (5.6 x 5.6 mm) arrays fixed on the surfaces of primary sensory areas in rabbits trained to discriminate visual, auditory, or tactile conditioned stimuli. EEG preprocessing was by (i) band pass filtering to extract the beta-gamma range (deleting theta-alpha); (H) low-pass spatial filtering (not high-pass Laplacians used for localization), (iii) spatial averaging (not time averaging used for evoked potentials); (iv) close spacing of electrodes for simultaneous recording in each area (not sampling single signals from several areas); (v) calculating variances among patterns in 64-space derived from the 8 x 8 arrays (not by fitting equivalent dipoles). These methodological differences were essential to reveal discontinuities in cortical activity: "state transitions". Each transition began with an abrupt phase re-setting, followed sequentially by resynchronization, stabilization of a spatial pattern of amplitude, and dramatic increase in global pattern amplitude. State transitions recurred at irregular intervals in the theta range. An estimate of perceptual information in the beta-gamma EEG disclosed 2 to 3 patterns with high information content in each trial that began with a state transition, lasted approximately 0.1 s, and recurred at theta rates. PMID- 17271307 TI - Walking through a virtual city by thought. AB - This paper gives a short overview of the feasibility of walking through a virtual city by using motor imagery. Therefore an electroencephalogram-based brain computer interface (BCI) is combined with virtual reality technology. A BCI transforms bioelectrical brain signals, modulated by mental activity (e.g. imagination of foot or right hand movements), into a control signal. This signal is used to walk forward / backward or to remain stationary inside a virtual city. Results of the first experimental sessions are presented. PMID- 17271308 TI - Lead selection for SSVEP-based brain-computer interface. AB - SSVEP-based brain-computer interface (BCI) has potential advantage of high information transfer rate. However, individual difference greatly affects its practical applications. This paper presents a method of lead selection to improve the applicability of SSVEP-based BCI system. Independent component analysis (ICA) is employed to decompose EEGs over visual cortex into SSVEP signal and background noise. Optimal bipolar lead is selected by comparing signal correlation and noise correlation between different channels. The system with one optimal bipolar lead has reached an average transfer rate about 42 bits/min for normal subjects. It has also been successfully applied to an environmental controller for the motion disabled. PMID- 17271309 TI - Improving speed and accuracy of brain-computer interfaces using readiness potential features. AB - To enhance human interaction with machines, research interest is growing to develop a 'brain-computer interface', which allows communication of a human with a machine only by use of brain signals. So far, the applicability of such an interface is strongly limited by low bit-transfer rates, slow response times and long training sessions for the subject. The Berlin Brain-Computer Interface (BBCI) project is guided by the idea to train a computer by advanced machine learning techniques both to improve classification performance and to reduce the need of subject training. In this paper we present two directions in which brain computer interfacing can be enhanced by exploiting the lateralized readiness potential: (1) for establishing a rapid response BCI system that can predict the laterality of upcoming finger movements before EMG onset even in time critical contexts, and (2) to improve information transfer rates in the common BCI approach relying on imagined limb movements. PMID- 17271310 TI - Improving neural prosthetic system performance by combining plan and peri movement activity. AB - While most neural prosthetic systems to date estimate arm movements based solely on the activity prior to reaching movements during a delay period (plan activity) or solely on the activity during reaching movements (peri-movement activity), we show that decode classification can be improved by 56% and 71% respectively by using both types of activity together. We recorded from the pre-motor cortex of a rhesus monkey performing a delayed-reach task to one of seven targets. We found that taking into account the time-varying structure in peri-movement activity further improved performance by 15%, while doing the same for plan activity did not improve performance. We also found low correlations in activity between pairs of simultaneously-recorded units and across time periods within a given trial condition. These results show that decode performance can be significantly improved by combining information from the plan and peri-movement periods, and that there is nearly no loss in performance when assuming independence between units and across tune periods within a given trial condition. PMID- 17271311 TI - An information theoretic approach for optimizing the analysis of multi-electrode multi-unit neuronal recordings. AB - This paper introduces an information theoretic approach for reducing the dimension of the observation space of multiunit neuronal responses recorded by high-density microelectrode arrays in the nervous system. The technique relies on selectively processing electrode channels that record neuronal responses to common information content without actually sorting the spikes. It exploits the statistical dependency of the data by maximizing the likelihood of observing covariance structures given a set of distance measures of the mutual information between the selected data channels. The strength of the proposed technique relies on the ability to measure mutual information of mixtures of neuronal responses to allow the selectivity to take place. Our preliminary results demonstrate that appropriate selection of data channels sharing common information prior to sorting the individual neuronal spike trains is feasible. Accordingly, substantial savings in computational costs and minimized user intervention are obtained compared to raw data transmission for off-line analysis. PMID- 17271312 TI - Model-based decoding of reaching movements for prosthetic systems. AB - Model-based decoding of neural activity for neuroprosthetic systems has been shown, in simulation, to provide significant gain over traditional linear filter approaches. We tested the model-based decoding approach with real neural and behavioral data and found a 18% reduction in trajectory reconstruction error compared with a linear filter. This corresponds to a 40% reduction in the number of neurons required for equivalent performance. The model-based approach further permits the combination of target-tuned plan activity with movement activity. The addition of plan activity reduced reconstruction error by 23% relative to the linear filter, corresponding to 55% reduction in the number of neurons required. Taken together, these results indicate that a decoding algorithm employing a prior model of reaching kinematics can substantially improve trajectory estimates, thereby improving prosthetic system performance. PMID- 17271313 TI - An automatic method to generate ensemble averages of movement-related potentials for individuals with spinal cord injuries. AB - Ensemble averaging of the electroencephalogram is known to be a good tool for characterizing various event related potentials. An important part of ensemble averaging is to know the time reference that the signals should be averaged. In able-bodied individuals the muscle activity or switch activation is used to time lock the averages. In people with spinal cord injuries who lack the ability to produce muscle activity, the expected time of the attempted movement based on an external cue can be used. This time is not accurate and can result in poor ensemble averages. A method that automatically detects the onset of the movement related potentials and use this knowledge to time-lock the averages is introduced. This method is based on the estimation of the probability density distribution of the feature vectors related to spontaneous EEG. To estimate the probability density function Parzen's method is used which is known to be as the most accurate method when large population of data is available. Preliminary experiments demonstrate the feasibility of the proposed method and show that the proposed method could generate ensemble averages closer to the averages with muscle activity knowledge than the method based on an external cue. PMID- 17271314 TI - Home monitoring of computer interactions for the early detection of dementia. AB - Standard cognitive assessments to detect dementia are administered infrequently and often long after symptoms are clear to even family members. With the advent of new drugs and therapies to delay the onset of dementia, it is important to both detect signs as early as possible and to provide monitoring of cognitive changes. This paper describes unobtrusive methods for monitoring user interactions with a computer that serve as a basis for algorithms to measure cognitive performance. We adapted a standard computer game currently enjoyed by elders at risk for dementia in order to monitor natural performance on a task that involved significant strategic planning throughout the game. This enabled us to collect cognitive performance data on individuals at frequent intervals. We monitored move-by-move appropriateness as distance to solution, and additionally modeled user thought processes using between-move data from the mouse device. We then used our resulting dynamic user model both to adapt the game difficulty and to detect meaningful individual cognitive trends. PMID- 17271315 TI - Approximate entropy of EEG as a measure of cerebral ischemic injury. AB - No doubt a noninvasive technique for detection of focal cerebral ischemic extent, before the focus is formed, is extremely valuable. A new approach to cerebral ischemic state analysis by approximate entropy is described in this paper. After a brief introduction to the concept, the approximate entropy, ApEn, were extracted from two different EEG time series, based on a novel cerebral ischemia experiment model of SD rat. Then the entropy values were analyzed, and the results showed that this measure of EEG complexity is sensitive to the extent of ischemic cerebral injury, ischemic and normal region can also be distinguished. PMID- 17271316 TI - Physiological noise in near-infrared spectroscopy: implications for optical brain computer interfacing. AB - Near-infrared spectroscopy is a non-invasive optical method used to detect functional activation of the cerebral cortex. Cognitive, visual, auditory and motor tasks are among the functions that have been investigated by this technique in the context of optical brain computer interfacing. In order to determine whether the optical response is due to a stimulus, it is essential to identify and reduce the effects of physiological noise. This paper characterizes noise typically present in optical responses and reports signal processing approaches used to overcome such noise. PMID- 17271317 TI - A new adaptive technique of estimation of steady state auditory evoked potentials. AB - A novel technique of fast estimation of steady state auditory evoked potentials (SSAEPs) for rapid assessment of the functionality of the human auditory nervous system is presented. The proposed SSAEP signal estimation is based on a new nonlinear adaptive signal processing method that has shown a great promise in the fast extraction of weak signals buried under large amounts of noise. Currently, the main technical impediment in the widespread clinical use of the SSAEP testing for hearing assessment is the excessively long measurement time needed for the estimation process due to the presence of large amounts of background noise. The studies in this paper show significant reduction in the measurement time achieved by the proposed technique. PMID- 17271318 TI - A dual-task approach to the evaluation of the myokinemetric signal as an alternative to EMG. AB - EMG is the signal widely used in neuromuscular control, biofeedback and measurement applications. Alternative physiological signals are available, but are used relatively infrequently. In the development of assistive devices, such as functional electrical stimulators, it is important to make the device as straightforward to use as possible. This is particularly relevant for patients with neurological and often associated cognitive impairments. Different physiological signals may require different degrees of attention to control, and advantage could be gained from selection of a signal that requires the least attention to control. However, relatively little work has been carried out on how to assess the demands of different physiological signals. This paper reports on the development of a novel experimental set up designed to address this problem and, in particular, to compare two different physiological signals, the EMG and the so-called MK signal. The paper presents the hardware design, including mechanical, electronic and software design, which involves data acquisition, parallel tasks and user-friendly interface. The system described could be adapted for evaluation of other physiological signals. PMID- 17271319 TI - A reduced complexity integer lifting wavelet-based module for real-time processing in implantable neural interface devices. AB - In high-density implantable microelectrode arrays, the sheer amount of data recorded poses a serious challenge to the bandwidth of the associated biotelemetry system. The power limitations and restricted chip area for an implantable module strongly imposes significant limitations on the computational complexity. In this work, we propose a new methodology for processing multichannel neural data most suitable for hardware implementation. Our work builds on previous work aimed at using the discrete wavelet transform (DWT) compact representation of the acquired neural data. We propose a novel design of the DWT computational block in a neural interface module and evaluate its performance in terms of speed, complexity and fidelity of the reconstructed signals. We show that most of the computations in this block can be performed with fixed-point representations and finite precision without significant loss in performance compared to the traditional floating-point computations in standard DSP chips. PMID- 17271320 TI - Using pitch accenting to improve Japanese text-to-speech understanding. AB - In order to develop an assistive technology that can increase computer accessibility for visually impaired people, we investigated the effect of pitch accenting on Japanese text-to-speech understanding. The effect was confirmed when a training procedure was introduced. Besides, we proposed an individual-adaptive pitching accenting method to explore the optimal pitch accents for individual users. The exploration process of one subject in a verification experiment was analyzed. PMID- 17271321 TI - Modified spike-triggered averaging to assess rat auditory cortex time-frequency receptive fields. AB - Receptive fields have been used as a tool to study the functional organization of the auditory system in several animals. In this study, they have been used to characterize the primary auditory cortex of rats, specifically to address the differences in auditory processing at different depths of the cortex. The depths chosen; 500, 800 and 1300 microm correspond to layers IV, V and VI of the cortex. This study aims at quantifying the differences in the receptive field in terms of changes in latency, differences in tuning curves, spectral bandwidth and the complexity of the receptive fields. The following preliminary trends were observed: the mean peak latency changes from 10 +/- 4 ms at a depth of 500 microm to 46 +/- 13.08 ms at a depth of 1300 microm. Mean spectral bandwidth changes from 6.4 +/- 0.95 kHz at 500 microm to 8.9 +/- 1.73 KHz at 800 microm to 8 +/- 2.53 KHz at 1300 microm. The mean temporal width changes with increasing depth from 13.6 +/- 1.15 ms at 500 microm to 9.4 +/- 1.88 ms at 1300 microm. Quantitative characterization of the receptive field can be used to generate mathematical models of the auditory neurons, which could aid the computation of stimulation levels for implantable cortical prosthetics. Preliminary data from our experiment on three animals has been presented here. PMID- 17271322 TI - An implementation of a simple neuron model in field programmable analog arrays. AB - A minimal neuron model, the Morris-Lecar model, is implemented on field programmable analog arrays (FPAAs). Our approach is to solve the differential equation describing the model in a similar way a computer solves the same problem: numerically integrate the differential equation by making arithmetic operations on voltage mode circuits of the FPAAs. The results demonstrate that biologically relevant dynamics can be observed from the electronic neuron despite limitations on the configurability of the FPAAs. Such models can be run accurately in real-time or many orders of magnitude faster than real-time. FPAAs are feasible candidates for implementation of neuron models using off-the-shelf software-reconfigurable analog circuit elements. PMID- 17271323 TI - Principal component analysis of temporal and spatial information for human gait recognition. AB - Principal component analysis was applied to human gait patterns to investigate the role and relative importance of temporal versus spatial features. Datasets consisted of various limb and body angles sampled over increasingly long time intervals. We find that spatial and temporal cues may be useful for different aspects of recognition. Temporal cues contain information that can distinguish the phase of the gait cycle; spatial cues are useful for distinguishing running from walking. PCA and related techniques may be useful for identifying features used by the visual system for recognizing biological motion. PMID- 17271324 TI - A biologically inspired model of binocular control on a free head. AB - A single layer, symmetrical bilateral controller with dual modalities has been developed for a robotic head, based on symmetries in brainstem circuits for the oculomotor control system (OCS). This robotic head controller is unique in the biological approach during its development, and its structural elegance afforded by the single layer organization. Extensions to this controller are based on connections between brainstem and cerebellar structures, and the OCS circuit. To make the robotic head better reflect biology: 1. velocity feedback is added to account for floccular projections to the brainstem OCS, and 2. integral feedback is added to represent findings of vector averaging mechanisms in superior colliculus. The resulting OCS controller has a structure better matched with what has been reported in brainstem premotor-circuit topology. The new bilateral OCS not only retains the structural and analytical simplicity of its precursor, but it now has an improved bandwidth for its pursuit mode, and can track faster objects with smaller errors, while requiring fewer saccades. PMID- 17271326 TI - A model of the respiratory central pattern generator. AB - We have developed a model of the mammalian respiratory central pattern generator (rCPG) to mimic the salient characteristics of its constituent medullary neurons. This model was designed as a network of Hodgkin-Huxley type medullary neurons under the hypothesis that synaptic and network effects predominate over ionic influences in determining the pattern of firing seen in individual neurons. After obtaining satisfactory mimicry of these patterns we validated the model to a different set of data in order to examine its robustness in the face of transient perturbations. PMID- 17271325 TI - Inferring direction of figure using a recurrent integrate-and-fire neural circuit. AB - Several theories of early visual perception hypothesize neural circuits that are responsible for assigning ownership of an object's occluding contour to a region which represents the "figure". Previously, we presented a Bayesian network model which integrates multiple cues and uses belief propagation to infer direction of figure (DOF) along an object's occluding contour. In this paper, we use a linear integrate-and-fire model to demonstrate how such inference mechanisms could be carried out in a biologically realistic neural circuit. The circuit, modeled after the network proposed by Rao, maps the membrane potentials of individual neurons to log probabilities and uses recurrent connections to represent transition probabilities. The network's "perception " of DOF is demonstrated for several examples, including perceptually ambiguous figures, with results qualitatively consistent with human perception. PMID- 17271327 TI - Model of the effect of extracellular fields on spike time coherence. AB - Accurate spike timing is emerging as an important concept in the encoding of sensory stimuli. Accurately timed spiking has been recorded in-vivo in the visual and auditory cortex, many layers removed from the primary sensory neurons. This temporal accuracy may be maintained despite noisy synaptic transmission by the simultaneous firing of multiple neurons. Here we show in simulations that a coherent polarization of a population of neurons through extracellular fields can further increase the coherence of the population's firing times. We discuss the potential relevance of such a common input as an external "clock" signal in a spatio-temporal code. PMID- 17271328 TI - A study for the hierarchical artificial neural network model for Giemsa-stained human chromosome classification. AB - A hierarchical multi-layer neural network with an error back-propagation training algorithm has been adopted for the automatic classification of Giemsa-stained human chromosomes. The first step classifies chromosomes data into 7 major groups based on their morphological features such as relative length, relative area, centromeric index, and 80 density profiles. The second step classifies each 7 major groups into 24 subgroups using each group classifier. The classification error decreased by using two steps of classification and the classification error was 5.9%. The result of this study shows that a hierarchical multi-layer neural network can be accepted as an automatic human chromosome classifier. PMID- 17271329 TI - Using neural network and principal component analysis to study vowel recognition with temporal envelope cues. AB - Previous studies in normal-hearing and cochlear-implant subjects have shown high levels of speech recognition with primarily temporal envelope cues. The present study used principal component analysis (PCA) to extract important features in temporal envelopes and then constructed a 3-layer feedforward artificial neural network to study their role in vowel recognition. Twelve vowels by 30 speakers in a /hVd/ context served as the test material. Temporal envelopes from 1 to 8 spectral bands were extracted and subjected to PCA with 15 principle components. Similar to previous perceptual data, the present study showed that 63% correct vowel recognition was achieved with only 4-band envelope cues. The principle components responsible for this high level of vowel recognition included phonemic transition cues and steady-state amplitude cues. The present result can be applied to the development of novel algorithms to improve performance for automatic speech recognition and auditory prosthetic devices. PMID- 17271330 TI - Characterizing neuronal firing patterns in the human brain. AB - A procedure to characterize firing patterns of neuron spikes from the human brain, in both temporal domain and the frequency domain, is presented. The combination of multitaper spectral estimation and the polynomial curve-fitting method is employed to transform the firing patterns to the frequency domain. To generate temporal shapes, eight local maxima are smoothly connected by cubic spline interpolation. We then used a rotated principal component analysis, which removes the orthogonality constraints of traditional PCA, to extract common firing patterns as templates from around 4100 neuron spike signals. Dynamic time warping was used to assign each neuron firings into the closest template without shift error. This technique can be utilized for finding firing similarities in neuroscience applications and in development of a query system. PMID- 17271331 TI - Long-term depression is reliably induced in rats at 30 days of age. AB - Previously we showed that long-term depression (LTD, a lasting diminishment in synaptic strength) can be reliably induced in the hippocampal dentate gyrus of both adult and 2-week old freely moving rats. Results from these studies indicated both age- and frequency-dependent alterations in the frequency response profile of the perforant path/dentate gyrus synapse. In the present study, we designed experiments to assess whether these frequency-response changes are sustained over the extent of time spanning the perinatal period and early adulthood. Dentate evoked field potentials were recorded and analyzed using the population spike amplitude (PSA) measure following sustained stimulation (900 pulses) of the lateral perforant pathway at various frequencies. Preliminary results suggest that LTD can reliably be induced in the 30-day old freely moving rat, and that such LTD is frequency dependent. These preliminary results, although representative of only 5 animals, appear to be consistent with our previously published findings of frequency and age effects on LTD transition to long-term potentiation (LTP) in the freely moving rat model. PMID- 17271332 TI - Information rate of neural spike trains in response to electric stimuli. AB - This article presents an analysis of the information rate of neural spike trains in an auditory nerve fiber (ANF) model stimulated extracellularly by colored Gaussian electric stimuli. In the analysis, stimulus current waveforms were generated by convolving alpha's functions with some alpha's parameters (the inverse of time constants) to white Gaussian processes, and were presented repeatedly to a stimulating electrode located 1 mm above the 26th node of Ranvier, in an ANF axon model having 50 nodes of Ranvier, each consisting of stochastic sodium and potassium channels. From spike firing times recorded at the 36th node of Ranvier, the inter spike intervals were generated and then "total" and "noise" entropies were estimated to obtain the mutual information and information rate of the spike trains. In the present article, it is shown that at a specific alpha parameter, the information rate was found to be maximized. It was implied that setting stimulus parameters to the specific values which maximize the information rate might contribute to efficiently encoding information in neural prostheses. PMID- 17271333 TI - Neuron selection and visual training for population vector based cortical control. AB - We have developed a method for training animals to control artificial devices from cortical signals. In this report we describe a series of experiments designed to parameterize a cortical control algorithm without an animal having to move its arm. Instead, a highly motivated animal observes as the computer drives a cursor move towards a set of targets once each in a center-out task. From the neuronal activity recorded in this visual following task, we compute preferred directions for the neurons. We find that the quality of fit in this early set of trials is highly predictive of each neuron's contribution to the overall cortical control. PMID- 17271334 TI - The use of artificial neural networks in the motor program. AB - Though it is commonly assumed that the brain creates "motor programs" which store the information essential to perform a motor skill, little direct evidence exists for such motor programs. Electromyography (EMG) provides a look into the motoneurons--level of a movement by measuring the electrical activity in relation to the muscle's involvement in the movement In this paper, artificial neural networks (ANNs) were applied to define the temporal patterns of EMG activity used by normal subjects in performing step-tracking tasks, and how such patterns change with practice. Our results demonstrate that ANNs could be trained to detect the input-output relationship between muscles' onset times and reaction times, and provided evidence to support the existence of a motor program. PMID- 17271335 TI - Model-based development of a user control algorithm for postural control via a FES-based standing neuroprosthesis. AB - The goal of this study was to devise an algorithm that would allow the user of a functional electrical stimulation (FES)-based neuroprosthesis to command desired transitions in body center of mass (COM) via smooth changes in lower extremity joint angles. Simulations were performed with a musculoskeletal model modified to reflect an individual with thoracic spinal cord injury, as well as the use of a 16 channel FES system. These simulations indicated useful subsets of 16 muscles, and a set of four polynomial surfaces were fit through the space relating COMx, COMy, and each of the four lower extremity joint angles studied. These polynomial surfaces provided a robust method for selecting a particular, smooth trajectory through this space. These results indicate that a 16-channel FES system should be capable of allowing users to shift postures over a significant fraction of the forward-backward range used by able-bodied individuals during typical activities. PMID- 17271336 TI - Hierarchical optimal control of redundant biomechanical systems. AB - Sensorimotor control occurs simultaneously on multiple levels. We present a general approach to designing feedback control hierarchies for redundant biomechanical systems, that approximate the (non-hierarchical) optimal control law but have much lower computational demands. The approach is applied to the task of reaching, using a detailed model of the human arm. Our hierarchy has two levels of feedback control. The high level is designed as an optimal feedback controller operating on a simplified virtual plant. The low level is responsible for transforming the dynamics of the true plant into the desired virtual dynamics. The new method may be useful not only for modelling the neural control of movement, but also for designing functional electric stimulation systems that have to achieve task goals by activating muscles in real time. PMID- 17271337 TI - Development of clinician-friendly software for musculoskeletal modeling and control. AB - Research and development in various fields dealing with human movement has been hampered by the lack of adequate software tools. We have formed a core development team to organize a collective effort by the research community to develop musculoskeletal modeling software that satisfies the requirements of both researchers and clinicians. We have identified initial requirements and have developed some of the basic components. We are developing common standards to facilitate sharing and reuse of musculoskeletal models and their component parts. Free distribution of the software and its source code will allow users to contribute to further development of the software as new models and data become available in the future. PMID- 17271338 TI - A Bayesian approach to biomechanical modeling to optimize over large parameter spaces while considering anatomical variability. AB - We present the Markov chain Monte Carlo (MCMC) approach in the context of a musculoskeletal model of the thumb. With special consideration for the complexities of biomechanical modeling, we present this approach as an alternative to standard parameter estimation techniques that produce a single, in some way optimal, set of parameter values. In contrast, MCMC methods are derived from a Bayesian philosophy, in which each "true" model parameter is actually a random variable with its own probability distribution. With MCMC we can (1) address challenges of model parameter estimation that are difficult for gradient based methods to meet, (2) estimate the inherent biomechanical capabilities of a specific "model topology" for large, variable parameter spaces (e.g. 50 dimensional for the assumed thumb model), and (3) determine the functional consequences of the unavoidable anatomical variability across subjects in a population. Using the MCMC approach with a Metropolis-Hastings sampling algorithm we explored a 50-D musculoskeletal parameter space and successfully achieved convergence. We found the relatively small subspace of the expansive 50-D space that, for a hinged serial linkage model of the thumb, predicts functional outcomes that best-fit the experimental data. PMID- 17271339 TI - Design of multiple degree-of-freedom sliding mode FES controller for concurrent stimulation of multiple mono and biarticulate muscles. AB - This article presents a theoretical design of an FES controller to be used for stimulation of multiple mono and biarticulate muscles to restore multiple degree of-freedom (DOF) motion in paralyzed individuals. The overall control strategy is based on multiple DOF musculo-skeletal model, nonlinear sliding mode control design, constrained optimization techniques to determine the needed muscle activations, and an additional inversion of the neuro-muscular stimulation relationship in order to obtain the needed controller output (electrical current amplitude/pulse-width). The combination of these methods leads to a controller that guarantees asymptotically stable tracking of reference position trajectories while assuring minimal (optimal) muscle activation and fatigue. PMID- 17271340 TI - A nonlinear tracking method of computing net joint torques for human movement. AB - Determining individual muscles forces from human performance has greatly depended on the quality of inverse dynamics solutions, as muscle force decomposition remains the only feasible approach for determining muscle forces non-invasively in human movement. However, legitimate questions about the accuracy of inverse dynamics arise, with resultant torques/forces failing to drive a forward model through the observations from which they were derived. While optimization of forward dynamics to match experimental data is considered more accurate, the simplicity and low computational costs of inverse methods are favored over the large computing requirements of optimization. In this paper, an evolution in the inverse methods for computing accurate and reliable torques is presented, whereby the relative speed of inverse dynamics is combined with the desired accuracy of forward dynamics. This method is based on developing a nonlinear tracker that determines the net muscle torques which accurately follow clinically observed kinematics and ground reaction forces. The results show that the method is robust and can produce accurate estimates of the joint torques during movement. The method outlined here is a necessary first step to solving the muscle force indeterminancy problem more efficiently. PMID- 17271341 TI - Analysis of the synergies underlying complex hand manipulation. AB - Coupling of actuators into motor synergies has been observed repeatedly, and is traditionally interpreted as a strategy for simplifying complex coordination problems. This view implies a small number of task-independent synergies. We have shown that optimal feedback control also gives rise to synergies in the absence of any simplification; the structure and number of such optimal synergies depends on the task. To compare these hypotheses, we recorded hand postures from a range of complex manipulation task. The structure of the synergies we extracted (via PCA) was task-dependent, and their number significantly exceeded previous observations in a simpler grasping task. Our results lend support to an optimal control explanation rather than a "simplicity" explanation. PMID- 17271342 TI - Internal models underlying fingertip force control during object manipulation in humans. AB - Since sensory information pertaining to an object's weight and weight distribution is not available until after an object has been grasped and lifted from its support surface, skillful manipulation requires predictive scaling of fingertip forces. The predictive control is based on internal models of the object formed during prior manipulatory experience. The present study investigates the extent to which such predictive control achieved with practice of one hand can be generalized to the contralateral hand. Subjects grasped and lifted an object instrumented with force transducers. The object's center of mass (CoM) was displaced 2 cm laterally from the object's center, requiring asymmetric partitioning of tangential force development to prevent tilting. They first performed five lifts using their right hand with the CoM located on a given side with a given weight. Then the subjects translated the object the left side of the body and performed one lift with the left hand. The procedure was repeated five times with the CoM located on each side of the object and with a total object weight of 400 g and 800 g. On the last pre-translation lift, the rate of tangential force development was appropriately higher in the digit opposing the CoM (p<0.05). In contrast, following translation to the left hand, the rate of tangential force development was nearly equal in each digit (p>0.05). Nevertheless the force rates were higher in both digits for lifts with the heavier (800 g) object (p<0.05). The results suggest there is a dichotomy between the generalizability of predictive control based on the object's weight and CoM. We propose that the control may be hierarchical in nature, with parameters that can be globalized representing higher level control and those that cannot (e.g., individuated digit control) representing a lower level control. PMID- 17271344 TI - Neuromuscular strategies for dynamic finger movements: a robotic approach. AB - Human hand control mechanisms are extremely complex and currently there is no solution to restore full function to a paralyzed hand. The optimal solution is to use either cortical signals or desired joint angles/torques to stimulate existing muscles. One of the limiting factors in achieving this goal is a poor understanding of the relationship between the input (i.e. neural signals to muscles) and the output (i.e. joint movements) in the system (i.e. hand). There are infinitely many sets of muscle forces that generate any given set of joint torques because of redundancy and the ability to co-contract antagonist muscles. In this paper, we describe a methodology to estimate and compare biological and robotic solutions for the muscle forces for a given set of dynamic joint movements. Our preliminary results indicate that the robotic solution obtained by finding the minimum forces resembles the biological solution. This methodology may allow us to identify the neuromuscular control strategies used during dynamic finger movements. PMID- 17271343 TI - Neuromuscular determinants of force coordination during multidigit grasping. AB - The biomechanical structure of the hand and its underlying neurophysiology contribute to the coordination of the kinematics and kinetics necessary for multidigit grasping. We recently examined the neural organization of inputs to different extrinsic finger flexors during multi-digit object hold and found moderate to strong motor unit short-term synchrony. This suggests a common neural input to the motoneurons innervating these different hand muscles/muscle compartments, which may in turn influence the coordination of grip forces. To further characterize this common input to the hand muscles during multidigit grasping, we used the frequency-based measure of coherence. Motor unit coherence provides information with regards to the oscillatory frequency of a common input, as well as the coupling of the discharges of a motor unit pair at both short and long latencies. Preliminary results indicate that a large proportion of trials are characterized by significant coherence in the 1-12 Hz frequency range, which is more pronounced in the within- than between-muscle/muscle compartment analysis. This indicates a differential organization of common oscillatory inputs to pairs of motoneurons innervating the same vs. different muscles/ muscle compartments. The functional role of the 1-12 Hz oscillatory modulation of motor unit behavior is currently being investigated. PMID- 17271345 TI - A computational environment to simulate complex tendinous topologies. AB - Static and dynamic manipulation of objects with the fingertips (precision pinch) is essential to the activities of daily living. Despite numerous efforts to study the hand and its pinch function, a comprehensive understanding of biomechanical function and neuromuscular control of the fingers eludes researchers. To make progress in understanding precision pinch we are creating biomechanical models to simulate finger function, neuromuscular control and rehabilitation. An important challenge in creating biomechanical models of the fingers is to simulate the tension distribution in the extensor mechanism--a defining biomechanical feature of the fingers consisting of a tendinous network that wraps over the dorsum of the phalanges. We have created a biomechanical modeling environment that can, among other things, predict tension distribution in the extensor mechanism. Our predictions show that the distribution of tension can be very sensitive to the assumed network topology--the number of elements and their connectivity. PMID- 17271346 TI - The effect of age on the grip force control in lateral grip. AB - In the paper we present the grip force tracking system for the evaluation of grip force control. We developed a grip measuring device which can be used for the computer assisted measurements of the grip force in real time. The device was used as an input to a force-tracking task where the subject applied the grip force according to the visual feedback from the computer screen. The performance of the task was evaluated by the tracking error between the target signal and the measured force. We assessed the grip force control in the groups of 10-year old children, 25- to 35-year old adults and 50- to 60-year old adults. The subjects performed a sinus tracking task which required periodic muscle activation to produce the desired output. The results of the average tracking errors show significant differences in grip force control among the three tested groups. The largest variability among subjects was observed in the group of children and older adults. No significant difference in force control was found between the dominant and non-dominant hand. The grip force tracking system presented is aimed to be used for the evaluation of grip force control in patients with different sensory-motor impairments. PMID- 17271347 TI - Biomechanical couplings between elbow and forearm movements. AB - Control of reaching task requires a strategy that takes into account biomechanical couplings in the musculoskeletal system. In a kinematic study, normal subjects were asked to reach to, grasp a cup, and bring it back. It was found that forearm rotation was coordinated in a particular manner with elbow motion in order to keep the cup in a leveled orientation. This coordination pattern may be due to the multi-axial actions of biceps muscles. A realistic model of human arm was used to examine the biomechanical constraints arising from musculature couplings in the coordination of elbow and forearm movements. Moment arm analysis indicated that biceps and brachioradialis have significant moment arms in forearm supination and pronation (S/P), which displays equilibrium point like neutral positions that vary with elbow angles. The dependency of S/P neutral positions with elbow angles in biceps is consistent with the coordination pattern observed between elbow and forearm movements during the reach and grasp in normal subjects. PMID- 17271348 TI - Disassociation between primary motor cortical activity and movement kinematics during adaptation to reach perturbations. AB - The relationship between movement kinematics and motor cortical activity was studied in monkeys performing a center-out reaching task during their adaptation to force perturbations applied to the wrist. The main feature of adaptive changes in movement kinematics was anticipatory deviation of hand paths in the direction opposite to that of the upcoming perturbation. We identified a group of neurons in the dorsal lateral portion of the primary motor cortex where a gradual buildup of spike activity immediately preceding the actual (in perturbation trials) or the "would-be" (in unperturbed/catch trials) perturbation onset was observed. These neurons were actively involved in the adaptation process, which was evident from the gradual increase in the amplitude of their movement-related modulation of spike activity from virtual zero and development of certain directional tuning pattern (DTP). However, the day-to-day dynamics of the kinematics adaptation was dramatically different from that of the neuronal activity. Hence, the adaptive modification of the motor cortical activity is more likely to reflect the development of the internal model of the perturbation dynamics, rather than motor instructions determining the adaptive behavior. PMID- 17271349 TI - The time course of functional coupling between human cortical motor areas during internally driven vs. externally cued movements. AB - The functional coupling between the primary motor cortex (M1) and the supplementary motor area (SMA) in the generation of internally paced versus externally cued rhythmic movements was explored using electroencephalography (EEG). This has important implications for the study of Parkinsonian patients who demonstrate decreased ability to perform internally paced rhythmic movement tasks. In particular, the temporal evolution of the coherence between M1 and SMA was studied using a recently developed time-frequency wavelet coherence algorithm. As this approach is not reliant upon pooling data from multiple trials to form a single estimate of the coherence for each subject, a subject by subject comparison is possible to determine subject specific frequencies of interest. It was found that at certain frequencies, the coupling between M1 and SMA was increased in the internally paced versus the externally triggered movement task. At only these specific frequencies did the peak of the coherence in the internal task precede that of the peak in the external task, which was time locked with the movement onset. This suggests a dual role of the M1-SMA coupling for both movement preparation and movement execution. PMID- 17271350 TI - Cortical contributions to the stretch reflex response in biceps brachii. AB - Long-latency components of the stretch reflex may aid in organizing multi-joint movements and posture. The aims of this study were to investigate if the M2 response in biceps brachii is mediated through a trans-cortical pathway. Ipsi lateral and contra-lateral transcranial magnetic stimulation, combined with a variety of ramp-and-hold perturbations in which the subject was instructed to either intervene or not resist were applied to biceps brachii. The biceps M2 response modulates with task and can be facilitated through contra-lateral TMS. This is consistent with the existence of a trans-cortical pathway. Attempts to inhibit this pathway, possibly affecting the long-latency stretch reflex have not yet produced consistent results. PMID- 17271351 TI - Muscle focus: a new biomechanical-based index on the selectivity of EMG activity and its application in quantifying the muscle coactivation patterns during isometric torque generation at the elbow and shoulder. AB - Electromyographic (EMG) recordings are widely used in the study of sensorimotor and neuromuscular systems, more specifically, in the measurement of the muscle activation patterns during isometric torque generation at the elbow and shoulder. In this paper, we introduce a new biomechanics based index of muscle focus. This new index quantifies the degree of selectivity in muscle activation during a shoulder/elbow motor task with a scalar. The muscle focus takes into account both muscle co-activation and muscle co-contraction (which is a special case of co activation caused by activation of agonist and antagonist muscles about a single joint). PMID- 17271352 TI - Abnormal intrinsic and reflex stiffness related to impaired voluntary movement. AB - We studied the relationship between mechanical abnormalities associated with spasticity and impairments in voluntary movements of the spastic joint in chronic, hemiparetic stroke subjects. System identification techniques were used to characterize the mechanical abnormalities of the elbow joint and to identify the contribution of intrinsic and reflex stiffness to these abnormalities. Repeated voluntary movements of the elbow from full flexion to extension at maximum speed were also conducted. These movements were quantified by measuring their kinematics parameters. The correlation coefficient was measured to determine the relationship between abnormal modulation of intrinsic and reflex stiffness as function of joint position with the kinematics parameters. We found that both intrinsic and reflex stiffness were significantly larger in stroke than control sides and were strongly position dependent, increasing with elbow extension. Abnormal modulation of intrinsic and reflex stiffness with position (slope) was correlated with an increase in duration of movement (DM), and a decrease in peak-velocity (Pv), peak-acceleration (Pa) and maximum voluntary contraction (MVC). Weakness, quantified as a decrease in MVC, was also correlated with the reduction in Pv, Pa and active range of motion (AROM). These findings demonstrate that abnormal modulation of both intrinsic and reflex stiffness with position are related to antagonist muscle weakness that may cause stroke patients to move slower and take longer to complete reaching tasks. PMID- 17271353 TI - Modulation of stretch reflex excitability during quiet human standing. AB - Stretch reflex excitability was measured during quiet standing by using a bilateral electro-hydraulic actuator to apply perturbations of angular position to the ankle. Subjects were instructed to stand quietly while pulse displacements were applied at random time intervals. Position, torque, gastrocnemius soleus EMG, tibialis anterior EMG, heel position, tibia angle, femur angle, and sacrum angle were measured. Activation level and reflex excitability varied substantially from trial to trial - reflex torque decreased as the background torque level increased; while reflex EMG increased when background torque increased. This behavior is consistent with previous findings in prone subjects. Reflex torque for a given activation level was found to vary with the initial torque derivative. Negative torque derivatives produced greater reflex excitation then their positive counterparts. These findings suggest that reflex excitability in quiet human standing is modulated to optimize balance. PMID- 17271354 TI - Time-varying parallel-cascade system identification of ankle stiffness from ensemble data. AB - Measurement of joint dynamic stiffness during time-varying conditions is crucial to understand the role of joint mechanics during movement. Stiffness can be separated into intrinsic and reflex components, and are modeled as linear dynamic and Hammerstein systems, respectively. Time-varying identification methods using ensemble data have been developed previously for both pathways and were tested separately on simulated data. In this study, these algorithms were integrated into the time-varying, parallel-cascade identification method. Ankle dynamics were modeled during a ramp input and simulated impulse response functions (IRFs) were generated. Gaussian white noise was low-pass filtered and was convolved with the simulated systems over 500 realizations. The ensemble data was used to evaluate the new identification technique. The mean variances accounted for (VAFs) between the true and identified IRFs for the intrinsic and reflex pathways were 99.9% and 97.7%, respectively, demonstrating the technique's strong ability to predict the system's dynamics. PMID- 17271355 TI - A distributed model of the saccadic system: simulations of trajectory variations produced by multiple competing visual stimuli. AB - When multiple competing visual stimuli are present, saccades show more trajectory variations than those produced by single-target stimuli. In particular, variable trajectories including curved and averaging saccades are observed when visual search is required to select and make a saccade to a target. In this paper, based on our behavioral observations and neural recordings in the superior colliculus (SC) in monkeys, we propose a new, distributed SC and cerebellum (CBM) model that accounts for the saccade trajectory variations produced by the presence of multiple visual stimuli. The long-range lateral inhibitory connections between SC units are replaced by local excitatory connections and short-range inhibition. The inhibition to the SC from the substantia nigra (SNr) is assumed to have distributed spatial tuning. The interactions between visually activated populations of SC units and the distributed SNr inhibition produce variable initial directions of saccadic trajectories and these directional variations are partially compensated by the CBM feedback system. PMID- 17271356 TI - Organization of the fibers in the dorsolateral funiculus of the cervical spinal cord in the cat. AB - To investigate the functional organization in the lateral corticospinal tract (LCST), the cervical white matter was stimulated with multiple penetrations in the mediolateral direction at the C5/C6 and C6/C7 segmental borders in cats. Silicon substrate microelectrodes (CNCT, University of Michigan) with a linear arrangement of activated iridium contacts were used. The stimulation current consisted of a short (10-20 ms) train of charge balanced biphasic pulses at 330 Hz. The evoked limb movements were observed and the activities from selected forelimb muscles were acquired into a computer. Only the data points with an activation threshold of less than 30 muA were considered in the analysis. The muscle contractions were usually in the form of short twitches. Sustained muscle forces were observed only rarely for certain movements such as elbow flexion and digit extension in the forelimb. There exits a region in the middle of the dorsolateral funiculus for both segments where the activation threshold was relatively high (>30 microA). A segregation of the fibers according to the muscles they innervate was not found in these segmental borders. A functional organization is being investigated with further analysis. PMID- 17271358 TI - Mechanical actions of individual muscles at the human elbow joint and their roles in protecting/unloading the ulnar collateral ligament. AB - Study of individual elbow muscles' mechanical actions is important in understanding the muscles' fundamental roles in performing various motor tasks. It also helps us gain insights into the compensatory mechanisms for elbow injuries like the ulnar collateral ligament (UCL) injury, which is a common sports-related injury. The mechanical actions of individual elbow muscles and their roles in loading/unloading the UCL were studied through in vivo experiments. PMID- 17271357 TI - Estimation of tibial and femoral 3D linear accelerations during gait. AB - Shock wave traveling through the skeletal are more and more considered in the development of articular disorders. A method to quantify those skeletal transients is to estimate body segment linear accelerations. However, linear accelerations magnitude is influenced by many factors such as location and fixation of sensors, walking velocity, walking level and also by wearing conditions. Hence, experimental results in literature can't be easily compared and normative data haven't been established yet. The present paper proposes a method to estimate three-dimensional (3D) tibial and femoral linear accelerations during treadmill walking. 15 able-bodied subjects were evaluated. 3D kinematics data recorded from an optoelectronic system (Optotrak 3010, Northern Digital, Canada) at knee joint level were derived to estimated 3D linear accelerations of the tibia and the femur at their respective coordinate system origins. PMID- 17271359 TI - Nonparametric identification of the elbow joint stiffness under compliant loads. AB - Several nonparametric system identification techniques have been used to estimate the dynamic joint stiffness of the human elbow. Most studies involved a very stiff environment, but some studies have also shown that stiffness is modified in response to environmental compliance. However, using the same identification technique used under very stiff conditions to do identification under compliant conditions leads to a biased estimate. This is due to the presence of feedback in the latter. In this paper, we use a nonparametric identification algorithm to demonstrate this problem. We then show how instrumental variables can be employed to obtain an unbiased estimate of the same. Both simulations as well as experimental data are used to this effect. PMID- 17271360 TI - Comparison of line length feature before and after brain electrical stimulation in epileptic patients. AB - This study aims to determine whether there are any statistically significant effects in the intracranial EEG signal due to brain electrical stimulation that can be quantified by comparing the line length value computed in windows positioned before and after stimulated abnormal events versus windows before and after non-stimulated abnormal events. The line length feature has been previously demonstrated to preserve waveform dimensionality changes as the ones estimated by Katz's fractal dimension and is a measure sensitive to variations in signal amplitude and frequency, equivalent in some ways to Teager's energy. Brief stimulation bursts of 200 Hz were delivered in response to some detections of abnormal electrographic activity. A total of 35 epileptic patients were analyzed including 15,938 electrographic events, of which 4,584 were electrically stimulated events. The ratio and difference of the post-stimulation versus the pre-stimulation line length values were computed as comparison measures. The average line length ratios in stimulated events versus those in non-stimulated events were lower in 23 out of 35 patients, suggesting that stimulation may have had an effect on electrographic activity. Statistical analysis based on a permutation test indicated the probability of finding this difference by random chance was 5.21%, further suggesting that the line length ratio differences are most likely due to the stimulation effects on the brain that manifest in the electrographic activity. PMID- 17271361 TI - Diffuse electrical injury: a study of sequelae as a function of gender. AB - Diffuse electrical injury (DEI) is a rarely occurring class of electrical injury that can arise even after a low voltage contact. It is characterized by broad symptomatology which is often disproportionate to the magnitude of the contact. The occurrence rate of 65 symptoms, categorized by gender, was studied. Data was derived from a Web-based interactive survey of individuals who suffered low voltage (<1000 volts) contacts and were more than six months post incident. Statistically significant differences (based on a Chi Squared test) among gender were noted for unexplained moodiness and short-term memory loss. For the majority of symptoms, no significant difference between the groups was revealed (P<0.05). Results suggest that although male and female DEI patients present with a similar symptom profile, DEI may present with certain differences in men compared to women. PMID- 17271362 TI - Enhanced spatio-temporal clustering in the detection of neonatal seizures using context-based rules. AB - This work describes the clustering stage of a three-stage automated neonatal seizure detection system. This stage clusters spatio-temporally the short candidate seizure segments detected in prior stages, and then applies a variety of context-based rules to eliminate false detections and determine the final detected seizures. The work discusses important considerations in the implementation of rules and presents preliminary results. PMID- 17271363 TI - Investigation of lapses of consciousness using a tracking task: preliminary results. AB - In many high-risk occupations, it is critical that a person remains alert at all times. There is much to be gained by being able to monitor a person on-line and detect lapses of consciousness (LoC) so that remedial action can be taken (e.g., a rest break) to ensure that safety is maintained. In this study, 15 normal subjects were observed on two sessions while they performed a continuous tracking task for a period of 1 hour. EEG, eye movements, tracking performance data and a video of the subject were recorded during the session. This work presents some preliminary results on the phenomenon of lapsing. Only 4 of the 15 subjects did not have a LoC at some stage. Seven subjects had LoCs more than 45 times and 4 more than 100 times during the 2 hours. The mean rate of lapsing over all subjects was 29.1 LoC/h. In contrast, lapses in performance were caused by both lapses of consciousness (30.1%) and attention (69.9%). There was no correlation found between age of subject and number of lapses of consciousness. PMID- 17271364 TI - A comparison of covert and overt attention as a control option in a steady-state visual evoked potential-based brain computer interface. AB - EEG data were recorded from occipital scalp regions of subjects who attended to an alternating checkerboard stimulus in one visual field while ignoring a similar stimulus of a different frequency in the opposite visual field. Classification of left/right spatial attention is attempted by extracting steady-state visual evoked potentials (SSVEPs) elicited by the stimuli to assess the potential use of such a spatial selective attention paradigm in a brain computer interface (BCI). Experimental setup and analysis procedure in a previous study in which eye movement is permitted are replicated in order to quantify differences in classification performance using overt and covert attention. Four variations of the basic paradigm, involving both feedback and addition of extra mental load, are studied for comparison. The average accuracy is found to be reduced by approximately 20% in the switch from overt to covert attention when no other specifications of the task are changed. PMID- 17271365 TI - High-frequency nerve conduction block. AB - High frequency alternating current waveforms have been shown to produce a rapidly reversible nerve block in animal models, but the parameters and mechanism of this block are not well understood. A frog sciatic nerve/gastrocnemius muscle preparation was used to examine the parameters for nerve conduction block in vivo. A complete and reversible nerve block was achieved in all preparations. The results indicate that a 100% block of motor activity can be accomplished with a variety of waveform parameters, including sinusoidal and rectangular waveforms at frequencies from 2 kHz to 20 kHz. The most efficient waveform for conduction block was a 3-5 kHz constant-current biphasic sinusoid. It was demonstrated that the block is not produced indirectly through fatigue. PMID- 17271366 TI - Electrode pressure application and measurement system during CMAP studies: preliminary results. AB - Parameters related to conduction velocity are more commonly assessed during CMAP studies excluding amplitude information. Our study suggests that the pressure on measurement electrodes could be responsible for variability in amplitude information during CMAP studies. A new device and method showed promise in CMAP amplitude reliability. PMID- 17271367 TI - Clinical evaluation of the tilt sensors feedback controlled FES for hemiplegia. AB - A feedback controlled functional electrical stimulation (FES) system is developed to provide the hemiplegic patients a real-time stimulation to their muscles to prevent the drop-foot and the quadriceps weakness from happening during gait training. The FES is controlled by tilt sensors (t.s.) and triggered by footswitches (f) with real-time feedback. As the FES receives the signals from these sensors, it adjusts and outputs an optimum set of stimulation parameters automatically. PMID- 17271368 TI - Dorsal column is not involved in the mechanism of the hypotensive effect by simulating acupuncture on rat hindlimb. AB - The present study investigated the role of the dorsal column (DC) in the mechanism of the hypotensive effect induced by simulating acupuncture on rat hindlimb. The femoral arterial pressure and electrocardiogram (ECG) of rats were recorded when the hypothalamic paraventricular nucleus (PVN) was electrically stimulated with or without DC lesion. Stimulation of the deep peroneal nerve (DPN) decreased the pressor response elicited by electrical stimulation of the PVN. Thirty minutes after micro-dissection of the right DC, the inhibitory effect of stimulating the right or left DPN on the pressor response induced by stimulation of the contralateral PVN was not altered. Of 6 rats tested, the inhibitory effect of stimulating the right or left DPN could still be observed five days after the right DC was destroyed. The pain responses of both hindlimbs of the rats with the right DC destroyed showed no obvious difference when compared with the sham control rats. These data suggest that the DC is not involved in the inhibitory effect of stimulating the DPN on the pressor response induced by the PVN activation. PMID- 17271369 TI - Validation of a computer-aided EMG decomposition method. AB - This paper presents an objective assessment of the accuracy of EMGLAB, a computer aided EMG decomposition program that we developed. EMG signals were recorded simultaneously using monopolar needle and fine-wire electrodes from nearby sites in the tibialis anterior muscle during moderate isometric contractions. The signals were decomposed independently by an experienced operator, yielding 3-12 (mean 8.7) motor-unit action potential (MUAP) trains per signal. Decomposition accuracy was estimated by crosschecking 83 pairs of trains from different signals that corresponded to the same motor units. The results show that EMGLAB was able to decompose large MUAPs (peak amplitudes greater than 2.5 times rms signal amplitude) with 98-100% accuracy, and smaller MUAPs with 80-100% accuracy. Many of the errors involved misalignment of small MUAPs within superimpositions and amounted to less than 5 ms. These results validate the accuracy of EMGLAB for decomposing EMG signals of moderate complexity. PMID- 17271370 TI - Melatonin reduced volume of cerebral infarct induced by photothrombosis in wild type mice, not in Cyclooxygenase-1 gene knockout mice. AB - Cyclooxygenase (COX) is crucial in inflammation and plays important role in cerebral ischemia. Antiinflammatory effects of melatonin have been verified in previous studies. In this study, cerebral blood flow (CBF) was monitored during operation, infarct volume (IFV) was determined with 5-triphenyltetrazolium chloride (TTC) staining and MR image, and neurological functions were evaluated with turn in an alley and fall pole test in both COX1-gene knockout and wide-type mice with or without melatonin administration 3 days after photothrombosis. CBF reduction, IFV and neurological deficits were not significantly different in COX 1 wild-type and COX-1 knockout mice. Melatonin (15 mg/kg) intraperitoneal injection decreased the CBF reduction, IFV and the latency to turn in an alley in COX-1 wide-type mice, whereas the neuroprotective effect of melatonin was attenuated in COX-1 knockout mice. We concluded that melatonin reduced susceptibility to photothrombotic stroke. COX-1 gene knockout does not alter the susceptibility to cerebral ischemia caused by photothrombosis. COX-1 plays an important role in the pathway of the protection of melatonin. PMID- 17271371 TI - PAM: passive marker-based analyzer to test patients with neural diseases. AB - Neurologists observed specific changes in the movement coordination of their patients - compared to healthy control subjects - a long time ago. In the early, preclinical phase the subtle changes cannot be detected by visual inspection. Similarly, variations in the performance of a patient resulting from minor changes in the stage of the disease remain undetected for the human observer. Evaluation of well-defined movement patterns aids the diagnosis even early diagnosis and assessment of the actual state of patients with neural diseases. Passive marker-based motion analysis is especially suitable for testing human movements. The markers are lightweight (1...10 grams), and no wires are needed between the markers and the analyzer. The markers and the analysis cause absolutely no discomfort to the persons. The performance of commercially available motion analyzers by far exceeds the requirements needed to record and evaluate the movement patterns of patients with neural diseases. As a consequence, these devices are too expensive for this purpose. A simple device has been developed that is affordable for routine clinical use. In harmony with the practice of neurologists, parameters have been defined that characterize both the speed and the regularity of movements. These parameters help in staging patients. PMID- 17271372 TI - Wearable conductive fiber sensor arrays for measuring multi-axis joint motion. AB - This paper describes a technique that uses conductive fibers as part of a wearable sensor for continuous monitoring of joint movements. Conductive fibers are incorporated into flexible fabrics that are comfortable and acceptable for long-term wear in everyday settings. Continuous monitoring of single or multi axis joint movement is therefore possible, even when not in the presence of a therapist. A brief overview of the sensor design is presented, including functional requirements and important design parameters. Misalignment errors that may be created every time the subject takes off and puts on the wearable sensor are accounted for by incorporating an array of fiber sensors around the joint and analyzing each sensor's sensitivity to joint movement during use. This eliminates any need for re-calibration after an initial calibration. PMID- 17271373 TI - Reconfigurable intelligent sensors for health monitoring: a case study of pulse oximeter sensor. AB - Design of low-cost, miniature, lightweight, ultra low-power, intelligent sensors capable of customization and seamless integration into a body area network for health monitoring applications presents one of the most challenging tasks for system designers. To answer this challenge we propose a reconfigurable intelligent sensor platform featuring a low-power microcontroller, a low-power programmable logic device, a communication interface, and a signal conditioning circuit. The proposed solution promises a cost-effective, flexible platform that allows easy customization, run-time reconfiguration, and energy-efficient computation and communication. The development of a common platform for multiple physical sensors and a repository of both software procedures and soft intellectual property cores for hardware acceleration will increase reuse and alleviate costs of transition to a new generation of sensors. As a case study, we present an implementation of a reconfigurable pulse oximeter sensor. PMID- 17271374 TI - Applications of vibrotactile display of body tilt for rehabilitation. AB - Body-mounted motion sensors have been shown to decrease subject sway when a tilt estimate is fed back to the user by means of an array of tactile vibrators which display estimated tilt magnitude and direction. Vestibulopathic subjects who are tested using computerized dynamic posturography show significantly reduced sway in both the sensory motor and the motor control portions of that test. This result suggests potential application as an assistive balance aid. Another potential application of vibrotactile tilt feedback is in rehabilitation. Two lines of research have yielded promising, albeit very preliminary, supporting results. The first of these is the response of subjects to a toes-up pitch maneuver. At critical pitch velocities, vestibulopathic subjects are unable to maintain stability during or after a perturbation without tilt feedback, but are able to stand when feedback is provided. The second line of research involves perturbations during locomotion. Vibrotactile tilt feedback again reduces subjects sway. Preliminary results of both of these on-going experiments indicate that this increase in performance may be retained. PMID- 17271375 TI - Data mining techniques to detect motor fluctuations in Parkinson's disease. AB - The purpose of this paper is to present preliminary evidence that data mining and artificial intelligence systems may allow one to recognize the presence and severity of motor fluctuations in patients with Parkinson's disease (PD). We hypothesize that movement disorders in late-stage PD present with identifiable and predictable features that can be derived from accelerometer (ACC) and surface electromyographic (EMG) signals recorded during the execution of a standardized set of motor assessment tasks. Although this paper focuses on a specific clinical application requiring advanced analysis techniques, the approach can be generalized to numerous applications in which data mining and other techniques can be used to analyze large data sets derived from wearable sensors. PMID- 17271377 TI - An interactive telemedicine system for remote speech-language pathology treatment. AB - There is significant potential for delivering speech-language pathology services using telemedicine methods. However, current telemedicine and videoconferencing equipment has limitations that constrain the speech-language therapeutic interventions that can be delivered remotely. This work aimed to develop a telemedicine system that would extend the capabilities of existing videoconferencing equipment and integrate an array of clinically relevant and validated therapeutic tools and techniques. Through a user-centered iterative design framework, an earlier prototype system was expanded and enhanced to enable greater interaction between a speech-language clinician and client during a telemedicine session. The final system utilizes H.323 Internet-based videoconferencing with integrated T.120 data sharing features and allows for a wide range of treatment material and therapeutic interventions to be delivered to a remote client. The protocol for a case-study evaluation designed to evaluate the system as a means for providing comprehensive speech-language treatment has been developed and testing is underway. Preliminary results indicate that the system is a viable alternative to face-to-face treatment for adult clients with neurological impairments. PMID- 17271376 TI - The influence of floor material on standing and walking by hemiplegic patients. AB - In this study, we evaluated the influence of floor materials on standing and walking in hemiplegic patients. To monitor body motion during standing and walking without any constraint, we used a measurement system that consisted of an accelerometer device, a telemeter system, and a personal computer. The posture angles in the antero-posterior and lateral directions were calculated from the low frequency component of the acceleration signal to evaluate body motion. Experiments were performed with six poststroke hemiplegic patients. We modified the time up and go test introduced by Podsiadle. The patients executed the task on three different floor materials: wooden flooring, linoleum, and carpet. The posture angle pattern on carpet differed from those on wooden flooring and linoleum. Therefore, the floor material influenced body motion. We suspect that this difference in movement corresponds to the hardness of the material. PMID- 17271378 TI - Progress toward universal interface technologies for telerehabilitation. AB - One of the overriding needs in the field of telerehabilitation is for user centered interfaces that provide individuals with differing abilities with access to effective remote communication. This paper provides a foundation for developing and evaluating interfaces that move towards the aim of universal accessibility, and reports on progress for four types of interfaces: multimedia conferencing technologies involving persons with different roles and disabilities participating in goal-directed tasks; physical devices for therapy and assessment; communication/control for computer-assisted teletherapy; and an intelligent telerehabilitation assistant that supports the dynamic rehabilitative process. PMID- 17271379 TI - Accelerometric activity identification for remote assessment of quality of movement. AB - This study examines acclerometric data collected during straight walking and stair climbing to assess a subject's mobility and activity level. Small, wearable accelerometers allow these motion analysis techniques to be used in a remote monitoring or telemedicine program. PMID- 17271380 TI - A remote assessment system with a vision robot and wearable sensors. AB - This paper describes an ongoing researched remote rehabilitation assessment system that has a 6-freedom double-eyes vision robot to catch vision information, and a group of wearable sensors to acquire biomechanical signals. A server computer is fixed on the robot, to provide services to the robot's controller and all the sensors. The robot is connected to Internet by wireless channel, and so do the sensors to the robot. Rehabilitation professionals can semi-automatically practise an assessment program via Internet. The preliminary results show that the smart device, including the robot and the sensors, can improve the quality of remote assessment, and reduce the complexity of operation at a distance. PMID- 17271381 TI - Monitoring functional arm movement for home-based therapy after stroke. AB - The goal of this project is to develop a means for individuals with stroke to practice arm movement therapy at home with remote monitoring. We previously developed a Web-based system for repetitive movement training (Java Therapy). This paper describes a new input device for the system that measures and assists in naturalistic arm movement, as well as software enhancements. The new input device is an instrumented, adult-sized version of Wilmington robotic exoskeleton (WREX), which is a five degrees-of-freedom orthosis that counterbalances the weight of the arm using elastic bands. To test the ability of the new device (Training-WREX or "T-WREX") to measure and assist in functional arm movements, we measured five chronic stroke subjects' movement ability while wearing the orthosis without gravity balance compared to wearing the orthosis with gravity balance. T-WREX's gravity balance function improved a clinical measure of arm movement (Fugl-Meyer Score), range of motion of reaching movements, and accuracy of drawing movements. Coupled with an enhanced version of Java Therapy, T-WREX will thus provide a means to assist functional arm movement training at home, either over the Web in real-time, or stand-alone with periodic communication with a remote site. PMID- 17271382 TI - A low cost method to measure finger flexion in individuals with reduced hand and finger range of motion. AB - The goal of this research is to evaluate a custom sensor glove that will be used to measure real-time finger flexion in individuals having a wide range of hand and finger function. A feasibility study of a low-cost prototype sensor glove has been performed in order to explore several specific requirements, including glove donning (ease of donning in individuals with moderate to severe restriction in hand motion), and glove comfort and durability (for up to 24 hours of continuous data collection). Results show that commercially available passive-resistive flex sensors contained in Lycra/Nylon sleeves can be used to collect real-time flexion data of each finger over extended periods of time. The individual sensor sleeves are securely attached to the back of each finger. This "sensor glove" demonstrates that data can be collected comfortably over an extended period of time while individuals perform daily activities away from the clinical site. Future work will investigate the repeatability of sensor glove measurements and the development of the wearable data recorder. PMID- 17271383 TI - Navigation system for visual impaired persons based on satellital location. AB - A system designed to assist visual impaired persons to travel in a city without external help using GPS navigation system has been developed. With the use of a BIuetooth hands-free, the user only has to give spoken commands to receive spoken directions to get to his/her destination. The directions received from the system will help him/her to walk parallel to the tangent of the walk-side and to walk through the most convenient route. This means that the route calculated to arrive to the destination point not only will be the shortest, but also the least risky one. The system can also be personalized by the user, entering his/her own waypoints. PMID- 17271384 TI - A portable audio-biofeedback system to improve postural control. AB - This paper introduces a portable audio-biofeedback (ABF) system that encodes the signals provided by a linear accelerometric sensor into a stereo sound. This sound is relayed to the subjects via headphones and can enhance the ability of subjects to perceive trunk accelerations. We tested this system on nine healthy subjects while they stood in three conditions listening to the ABF representation of their trunk accelerations. The ABF significantly improved the subjects' balance in all three conditions. The subjects reported that they were comfortable wearing and using the ABF device. Results suggest that devices such as this ABF system may be used for balance training and balance rehabilitation therapy. PMID- 17271385 TI - Evaluation of command sources for a high tetraplegia neural prosthesis. AB - One of the issues involved in the development of a neural prosthesis for high tetraplegia is that of an appropriate command interface between the user and prosthetic. With high levels of impairment come low levels of available voluntary actions suitable for issuing commands. Three potential command interfaces were investigated for their applicability to commanding endpoint position of a robot arm, as a proxy to a stimulated paralyzed arm. Head orientation as a command source was explored using both direct servo drive and gated ramp algorithms. EMG signals with a gated ramp algorithm from muscles in the face were also investigated as a potential command source. The information transfer rate (ITR) of all three command interfaces were evaluated using a 3D Fitts Law task. The resulting information transfer rate of the EMG interface was 0.55 Bits/sec, while both head orientation interfaces resulted in ITRs of 0.49 Bits/sec each. PMID- 17271386 TI - On the design of an exoskeleton for neurorehabilitation: design rules and preliminary prototype. AB - The neurorehabilitation robotics is a promising research field that allows improvements of the therapy effects. Some interesting systems for the neurorehabilitation of the upper limb are based on standard robotic arms and their applicability and effectiveness are based on the presence of patient's residual motor control synergy. On the other side, the exoskeletons overcome the single joint control allowing the full control of the arm kinematics. This paper presents the first results obtained at ARTS lab for the development of an exoskeleton for upper limb, starting from one of its building block that is a stand-alone active orthesis for functional assessment of the human wrist. We are addressing the design with a biomechatronic approach, based on an extensive analysis of the state-of-the-art. The design rules of sensorized wrist orthesis for functional assessment of the wrist and its first prototype are presented. PMID- 17271387 TI - Preliminary study on electrotactile sensitivity of the lips. AB - The sensitivity and discriminating ability of the lower lip have been evaluated In this preliminary study. Past psychophysical studies show that the lips are highly sensitive due to their large cortical mapping, leading one to envision a wearable lip-based tactile display that is easy to use and allows hands-free operation. As lips have never been utilized for tactile display applications, preliminary study on the sensitivity and discriminating ability of the lips is conducted on five human subjects. Three stimulator arrays of different sizes are utilized to present electrotactile patterns in experiments on measurement of sensory thresholds and rating of two-line separation. Experimental results show that the lips need very low intensities for effective electrotactile stimulation. As the stimulator diameter increases from 75 mum to 1.55 mm, the average stimulation intensity at the threshold level decreases from 11.6 V to 6.6 V for the lower lip, and the percentage of correct rating of spacing between two adjacent lines increases from 47.3% to 84.8%. The preliminary study will help to understand the electrotactile characteristics of the lips and to optimize the design of an electrotactile display with geometrical parameters suitable for lip stimulation. PMID- 17271388 TI - Assessment of muscle blood flow volume in elderly poststroke hemiplegic patients using near-infrared spectroscopy. AB - This study assessed the changes in blood flow volume in elderly hemiplegic patients before and after rehabilitation training. Total hemoglobin accumulation (blood flow volume) was measured using near-infrared spectroscopy (NIRS) in both the affected and unaffected gastrocnemius muscles before and after walking. In the gastrocnemius on the affected side, the blood flow volume was larger during the recovery period than during the rest period, and the blood flow volume did not decrease during the recovery period after the subjects walked a corridor. By contrast, the blood flow volume recovered faster on the unaffected side than on the affected side. After the subjects walked the stairs, the blood flow volume increased in the gastrocnemius muscles on both sides. These results suggested that the level of training involved in walking a corridor was too light for the unaffected side, although it was effective for the affected side. In our subjects, walking the stairs was effective rehabilitation training for both the unaffected and affected sides. Our results suggested that NIRS was an objective tool useful for planning rehabilitation training. PMID- 17271389 TI - Robotic gait training: toward more natural movements and optimal training algorithms. AB - This paper overviews our recent efforts to develop robotic devices to help people relearn how to walk after spinal cord injury. Our efforts are focused on two goals. The first is to develop robotic devices that allow natural gait movements and good force control. We have developed a five degrees-of-freedom robot (PAM) that accommodates natural pelvic movement during walking. PAM uses pneumatic actuators and a nonlinear control algorithm to achieve good force control. We have also developed a novel leg robot, ARTHuR, which makes use of a linear motor to precisely apply forces to the leg during stepping. Our second goal is to develop optimal training algorithms for robotic gait training. Toward this goal, we have developed a small-scale robotic device that allows us to test locomotor training techniques in rodent models. We have also developed an instrumentation system that allows us to measure how experienced therapists manually assist limb movement. Finally, we are developing computational models of motor rehabilitation. These models suggest that assisting in stepping only as needed with a force-controlled robotic device may be an effective method for improving locomotor recovery. PMID- 17271390 TI - Cooperative strategies for robot-aided gait neuro-rehabilitation. AB - Task-oriented repetitive movements can improve muscular strength and movement coordination in patients with impairments due to neurological or orthopedic lesions. The application of robotics and automation technology can serve to assist, enhance, evaluate, and document neurological and orthopedic rehabilitation of the lower and upper extremities. This review presentation will give an overview of patient-cooperative techniques to the robot-aided gait rehabilitation of paralyzed patients. Patient-cooperative means that the technical system considers the patient intention and efforts rather than imposing any predefined movement or inflexible strategy. It is hypothesized that cooperative approaches have the potential to improve the therapeutic outcome compared to classical rehabilitation strategies. Three new cooperative strategies are presented in this review. In all three strategies the patient's movement effort is detected and processed in three different ways. First, the data is used to offer the patient an increased freedom of movement by a certain amount of robot compliance. Second, the robot behavior is adapted to the patient movement efforts. In the third strategy the recorded movement data are displayed to the patient in order to improve the patient efforts by biofeedback principles. PMID- 17271391 TI - Upper and lower extremity robotic devices to promote motor recovery after stroke recent developments. AB - Successful motor rehabilitation of stroke, TBI and SCI subjects requires an intensive and task-specific therapy approach. Budget constrains limit a hand-to hand therapy approach, so that intelligent machines may offer a solution to further promote motor recovery and to better understand motor control. This new field of automated or robot-assisted motor rehabilitation has emerged since the nineties. The article presents clinically viable devices for the upper and lower extremity rehabilitation, which have been developed by our group. The Bi-Manu Track, enables the bilateral practice of a forearm and wrist movement, and is currently tested. For gait rehabilitation after stroke, the electromechanical gait trainer GT I has proven effective as compared to treadmill training with body weight support (BWS). The latest development is the HapticWalker, a robotic walking simulator for gait training, which allows the training of arbitrary daily life foot trajectories. The foot trajectories can be individually adjusted to each patient, in addition the machine will offer a sophisticated patient-machine interaction. A prototype of the machine has been designed and built succesfully and is being evaluated at present. Technical possibilities are one aspect, but multi-centre trials and the consideration of unsubstantiated fears among therapists of being replaced by the machines will decide on the successful implementation of this most promising field to the benefit of patients. PMID- 17271392 TI - Robotic-assessment of walking in individuals with gait disorders. AB - Walking deficits are a common bi-product of numerous neurological injuries, such as stroke and spinal cord injury. A number of new therapeutic interventions, such as body-weight supported locomotor training and robotic technologies aim to improve walking function and reduce co-morbidities. Currently, there is no way to determine what the optimal set of training parameters are for maximizing step performance. This paper presents a technique for estimating the walking performance of individuals with gait disorders using a robotic-orthosis. The device, called the Lokomat is coupled to the subject through instrumented leg cuffs, while the split-belt treadmill on which the subject walks is instrumented with piezo-electric force sensors allowing for the calculation of ground reaction forces and center of pressure. Using this data, a real-time inverse dynamics approach can be used to estimate the kinetics and kinematics of the subject, and when combined with electromyographic (EMG) data, the set of training conditions through which the subject generates the most appropriate EMG patterns and joint moments can be identified. The proposed technique will for the first time provide clinicians a way of determining the optimal gait training parameters for each individual, and also track their functional recovery throughout their neurorehabilitation program. It is postulated that training at the conditions that maximizes stepping performance will lead to higher gains in over-ground walking ability. PMID- 17271393 TI - Networked virtual environments and rehabilitation. AB - Virtual environments (VE) have been shown to be a powerful tool for various forms of rehabilitation. Currently, VE has been used in psychological training, motor recovery, visual relearning, and pain reduction during physical therapy. VE's use is also being explored in stroke rehabilitation coupled to robots, posture control in labyrinthine deficit patients, tele-rehabilitation and in other areas. Expanding VE's influence is its coupling with high-speed networking [tele immersion]. Current experimental networks have speeds approaching 100 Gb/sec. At these speeds the network bandwidth rivals that of the internal connections of a PC (i.e., bus speed). Accordingly, these new networks will permit various peripherals attached to computers on this network to be connected together and act as fast as if connected to a local PC. This innovation may soon allow the development of previously unheard of networked rehabilitation systems. This presentation will discuss various forms of VE that are currently available for rehabilitation. Furthermore, we will explain the characteristic of these new networks. Finally, we will examine how such networks might be used for extending the rehabilitation clinic to remote areas. PMID- 17271394 TI - Vestibular rehabilitation using a wide field of view virtual environment. AB - This paper presents a theoretical justification for using a wide field of view (FOV) virtual reality display system for use in vestibular rehabilitation. A wide FOV environment offers some unique features that may be beneficial to vestibular rehabilitation. Primarily, optic flow information extracted from the periphery may be critical for recalibrating the sensory processes used by people with vestibular disorders. If this hypothesis is correct, then wide FOV systems will have an advantage over narrow field of view input devices such as head mounted or desktop displays. Devices that we have incorporated into our system that are critical for monitoring improvement in this clinical population will also be described. PMID- 17271395 TI - Robotics and virtual reality: the development of a life-sized 3-D system for the rehabilitation of motor function. AB - We have been developing and combining state-of-art devices that allow humans to visualize and feel synthetic objects superimposed on the real world. This effort stems from the need of platform for extending experiments on motor control and learning to realistic human motor tasks and environments, not currently represented in the practice of research. This paper's goal is to outline our motivations, progress, and objectives. Because the system is a general tool, we also hope to motivate researchers in related fields to join in. The platform under development, an augmented reality system combined with a haptic-interface robot, will be a new tool for contributing to the scientific knowledge base in the area of human movement control and rehabilitation robotics. Because this is a prototype, the system will also guide new methods by probing the levels of quality necessary for future design cycles and related technology. Inevitably, it should also lead the way to commercialization of such systems. PMID- 17271396 TI - TheraDrive: a new stroke therapy concept for home-based, computer-assisted motivating rehabilitation. AB - Stroke results in functional arm impairments that persist even after rehabilitation training. The increasing numbers of persons at-risk in the population for stroke creates an increased need for therapy programs that can be effectively administered in both home and outpatient clinics. The aim of this work is to create a low-cost, commercially-viable, home-based rehabilitation system that can capitalize on computer-assisted motivating rehabilitation concepts of game therapy and skill training with functional training related to real activities to induce user-dependent CNS plasticity. The TheraDrive concept combines the motivational elements of relearning steering tasks with playing driving video games using commercial force-feedback steering wheels to create an upper arm stroke therapy environment that is usable at home or in the clinic. This paper presents the concept and reports on investigations to evaluate the main commercial building blocks for the prototype: the steering wheel and driving software. Evaluation results of three force-feedback steering wheels and the driving gaming software called SmartDriver are presented. Future evaluation trials with stroke subjects will be completed. PMID- 17271397 TI - Dual Stewart platform mobility simulator. AB - A robotic mobility simulator is being developed to allow training on various hapticly simulated surfaces while still being in the safe clinical environment. The simulator is integrated with a rich virtual environment displayed in front of the patient. The system uses two Stewart platform robots to render the walking surface geometry and condition. The hardware components of the platforms and the considerations behind their design are presented here. In addition, the nine state algorithm used for simulating the treadmill functioning is described along with the procedure used to transform the motion of the robots into walking in the virtual environment. PMID- 17271398 TI - Design and development of virtual reality based perceptual-motor rehabilitation scenarios. AB - Virtual reality technology may provide new options for conducting perceptual motor assessment within simulated 3D environments for persons with a wide range of disabilities. This paper outlines our work developing a series of game-like VR scenarios to assess and rehabilitate eye-hand coordination, range of motion and other relevant perceptual-motor activities. Our efforts have focused on building engaging game-based stereoscopic graphic scenarios that allow clients to participate in perceptual-motor rehabilitation by interacting with 3D stimuli within a full 360-degree space using a head mounted display or by way of a "face forward" format using 3D projection displays. Exploratory work using multiple video sensors to detect and track 3D body motion, identify body postures and quantify motor performance is also described. PMID- 17271399 TI - Outcomes of intervention programs using flatscreen virtual reality. AB - Virtual reality (VR) has the potential to offer experiences which are engaging and rewarding. In VR, the focus is shifted from the person's efforts in producing a movement or completing a task to that of interaction with the virtual environment. We have found that participants place value and meaning on and enjoy the activities programmed. Virtual reality interventions have been shown to improve cognitive function and concentration through an individual's interaction with a pleasant activity. Importantly, the enjoyment experienced while working with VR may increase the level of participation. In addition to generating realistic situations for testing, intervention and collection of data, the provision of immediate and positive feedback through VR has been shown to increase self esteem and empowerment. We will report outcomes from several intervention and feasibility trials using a flat screen virtual reality system with survivors of traumatic brain injury, community living older adults and children with spastic cerebral palsy. Gross motor movements were elicited through various game-like VR applications without the need for head-mounted displays or other peripherals. The impact of VR exercise participation ranged from improvements in clinical measures of functional balance and mobility, time on task, as well as participant and care provider perceptions of enjoyment, independence and confidence. Although still preliminary, our data suggest that simple applications of virtual reality have significant impacts on physical and psychosocial variables. Possibilities for and benefits of home and community based access to virtual reality based programs will be explored. PMID- 17271400 TI - Locomotor rehabilitation in a complex virtual environment. AB - Virtual reality (VR) technology offers a new and safe way to increase practice time and provide the varied environments and constraints needed to optimize locomotor training. Our specific objectives are (1) to create a virtual environment (VE) coupled with a self-paced treadmill for locomotor training; (2) to compare temporal and distance measurements of gait during treadmill walking while looking at different scenarios of VE; and (3) to develop a protocol optimized for the training of locomotor disorders after stroke. A motorized treadmill was mounted on a six-degree-of-freedom motion platform. VEs were created using commercial software (SoftImage) and projected on a large screen, while system control was administered through the CAREN software (Motek BV). The instantaneous treadmill speed and scene progression were servo-controlled. Preliminary results show that healthy subjects are able to have full control of their own walking speed both on the treadmill and within the virtual scene, while experiencing a strong sense of presence. A street crossing training protocol has been developed for locomotor training. It is expected that locomotor training with increasingly complex VEs will allow persons with stroke to increase progressively their locomotor capacity, as required and entrained by the VE. PMID- 17271401 TI - Postural research and rehabilitation in an immersive virtual environment. AB - We have united an immersive dynamic virtual environment with motion of a posture platform to record biomechanical and physiological responses to combined visual, vestibular, and proprioceptive inputs. A 6 degree-of-freedom force plate provides measurements of moments exerted on the base of support. Kinematic data from the head, trunk, and lower limb is collected using 3-D video motion analysis. The virtual image is projected via a stereo-capable projector mounted behind the back projection screen. This system allows us to explore complex behaviors necessary for rehabilitation. We are currently examining how a dynamic visual field affects posture and spatial orientation, and whether visual task demands interfere with our ability to react to a loss of balance in healthy adults and in adults with labyrinthine deficit. Our data suggest that when there is a confluence of meaningful inputs, none of the inputs are suppressed in healthy adults; the postural response is modulated by all existing sensory signals in a non-additive fashion. Labyrinthine deficient adults suppress visual inputs. Individual perception of the sensory structure also appears to be a significant component of the postural response in these protocols. We will discuss the implications of these results for the design of clinical interventions for balance disorders. PMID- 17271402 TI - Shaping synergistic pinching patterns with feedback distortion in a virtual rehabilitation environment. AB - Individuals with chronic disabilities often use compensatory coordination patterns learned during the recovery phase, even after their individual muscular control returns. Although these compensatory movements limit their ability to complete tasks, these individuals are not able to relearn the correct synergistic coordination patterns because doing so would temporarily compromise task performance. Following our previous work using feedback distortion in a virtual rehabilitation environment to increase the strength and range of motion of disabled individuals, we address the use of this same feedback distortion environment to alter movement coordination patterns. In this paper, we present the methodology and preliminary results showing that (1) able-bodied individuals could be trained to use a different coordination pattern to produce pinching movements, and (2) feedback distortion can alter movements for individual fingers separately during a coordinated movement. These results indicate that our distorted virtual environment may be a powerful rehabilitation tool to convert compensatory movements into movements that utilize all muscles in the normal synergistic patterns. PMID- 17271403 TI - Development of the visually impaired person guidance system using GPS. AB - Most of the visually impaired are able to walk independently, if they have the mental map of their walking area. However, in their unknown area, they cannot walk alone and they need a guide dog or help of others for walking. And not only a supporter of the visually impaired but a visually impaired person receives stress while walking. More over in Japan, there are about 300,000 visually impaired persons, and are about 900 guide dogs. These number of guide dogs are too few. Therefore, an auto navigation system for the visually impaired is required in Japan. Our objective is the development of the auto navigation system for the visually impaired. This navigation system obtains the position of an user (visually impaired user) by DGPS. From the digital map data base in our system and the position of an use are analyzed, and suitable route to the destination is calculated, and then our system guides the way to the destination to the user. In this paper, we'd like to report about our new navigation system for the visually impaired and report some experimental results of our system. From these results, we think our system will be a powerful for the visually impaired. PMID- 17271404 TI - Rehabilitative orthotics evaluation in children with diplegic cerebral palsy: kinematics and kinetics. AB - Ankle foot orthoses (AFOs) are prescribed for ambulatory children with spastic diplegia to improve biomechanical alignment and functional capability. The purpose of this study was to employ quantitative motion analysis of the lower extremity to investigate two rehabilitative orthotics. The effects of hinged ankle foot orthoses (HAFO) and dynamic ankle foot orthoses (DAFO) for joint ankle management in children with cerebral palsy were compared. Sixteen (16) independently ambulatory children with a diagnosis of spastic diplegic cerebral palsy (7.5 +/- 2.9 yrs.) were included in the study. The biomechanical effects of two AFO designs were compared to barefoot using a 3-D motion analysis system. Significant differences between braced and unbraced conditions were found in peak ankle dorsiflexion, and peak ankle plantarflexion, knee stance peak flexion, knee swing peak flexion, hip stance peak flexion, and peak ankle plantarflexion moment (p < 0.01). Differences between the HAFO and DAFO were not seen in the kinematic and kinetic metrics. Further development of dynamic testing is suggested in order to advance our understanding of orthotic intervention. The value of quantitative description of gait dynamics is clearly indicated for rehabilitative application. PMID- 17271405 TI - Simulation study of FES-assisted standing up with neural network control. AB - A neural network (NN) control system is designed for the functional electrical stimulation (FES) assisted standing up. A musculoskeletal model of nine muscles and three segments is constructed for the simulation study. Each muscle is controlled by the sub-network of the functional neural network. The sub-network is the radial basis function (RBF) NN. Minimal resource allocation (M-RAN) learning algorithm is used in the RBF NN design. This system aims to reduce the upper body effort and keep the body balance when the patient stands up. Promising simulation results provide the potential for feasible clinical application in the future. PMID- 17271406 TI - Optimized joystick controller. AB - The purpose of the study was to develop an optimized joystick control interface for electric powered wheelchairs and thus provide safe and effective control of electric powered wheelchairs to people with severe physical disabilities. The interface enables clinicians to tune joystick parameters for each individual subject through selecting templates, dead zones, and bias axes. In terms of hand tremor usually associated with people with traumatic brain injury, cerebral palsy, and multiple sclerosis, fuzzy logic rules were applied to suppress erratic hand movements and extract the intended motion from the joystick. Simulation results were presented to show the graphical tuning interface as well as the performance of the fuzzy logic controller. PMID- 17271407 TI - Biomechanics of femoral deformity in osteogenesis imperfecta (OI): a quantitative approach to rehabilitation. AB - Skeletal deformity is an important characteristic of osteogenesis imperfecta (OI). To study the influence of deformity in stress/strain distribution, a finite element analysis (TEA) of the femur during physiological loading was developed. The diaphysis was altered mathematically to reflect different clinical deformities of OI. Joint reaction and muscle forces were adapted from the literature to reproduce the loading environment at 10% gait cycle (loading response, LR). The goal of the study was to quantitatively describe the stress/strain distribution while comparing the extent of deformity. The results showed that deformity could deteriorate the stress/strain distribution. The study offers a quantitative means for rehabilitative intervention. PMID- 17271408 TI - Biofeedback in gait training with the robotic orthosis Lokomat. AB - Neurological diseases - such as spinal cord injury, stroke and traumatic brain injury - frequently result in gait impairment The recovery of the walking ability requires functional training (i.e. walking), as previous research in man and animal has shown. Because the patient usually has reduced voluntary muscle force early after the incident, his/her movements require external support by physical therapists or special robotic devices. The Lokomat is a robotic gait orthosis with electromechanical drives that supports walking on a treadmill with body weight support. Because the movements are performed according to a predefined trajectory, there is no visible cue to the amount the patient is contributing. However, the forces measured within the drives can deliver an estimation of this contribution. Based on these measurements, biofeedback on the patient's gait performance was added as a new feature. The visual display will allow the patient to get direct feedback on his/her efforts, and will allow the therapist to instruct the patient better. We report here that the biofeedback can correctly reflect the activity of a healthy subject, that patients can benefit from the use, and what the patients' opinion is. PMID- 17271409 TI - Real-time head movement system and embedded Linux implementation for the control of power wheelchairs. AB - Mobility has become very important for our quality of life. A loss of mobility due to an injury is usually accompanied by a loss of self-confidence. For many individuals, independent mobility is an important aspect of self-esteem. Head movement is a natural form of pointing and can be used to directly replace the joystick whilst still allowing for similar control. Through the use of embedded LINUX and artificial intelligence, a hands-free head movement wheelchair controller has been designed and implemented successfully. This system provides for severely disabled users an effective power wheelchair control method with improved posture, ease of use and attractiveness. PMID- 17271410 TI - Measurement of ankle spasticity in children with cerebral palsy using a manual spasticity evaluator. AB - Spastic hypertonia involving spasticity and/or contracture is a major source of disability in cerebral palsy and other neurological impairments like stroke. Several measures have been used to assess the reflex hyperexcitability and hypertonus associated with spasticity, including the Ashworth scale, tendon reflex scale, pendulum test, mechanical perturbations and passive joint ROM. These measures generally are either convenient to use in clinics but not quantitative or they are quantitative but difficult to use conveniently in clinics. We developed a manual spasticity evaluator (MSE) to evaluate the spasticity/contracture quantitatively and conveniently in a clinical setting. Using the MSE, we measured the ankle ROM at controlled low velocity, elastic stiffness, and Tardieu R/sub 1/ catch angle at different velocities. The results show decreased ROM and increased stiffness in spastic ankle, and the Tardieu R1 catch angle was approximately linearly related to the movement velocity. PMID- 17271411 TI - Development of the navigation system for visually impaired. AB - A white cane is a typical support instrument for the visually impaired. They use a white cane for the detection of obstacles while walking. So, the area where they have a mental map, they can walk using white cane without the help of others. However, they cannot walk independently in the unknown area, even if they use a white cane. Because, a white cane is a detecting device for obstacles and not a navigation device for their correct route. Now, we are developing the navigation system for the visually impaired which uses indoor space. In Japan, sometimes colored guide lines to the destination is used for a normal person. These lines are attached on the floor, we can reach the destination, if we walk along one of these line. In our system, a developed new white cane senses one colored guide line, and make notice to an user by vibration. This system recognizes the line of the color stuck on the floor by the optical sensor attached in the white cane. And in order to guide still more smoothly, infrared beacons (optical beacon), which can perform voice guidance, are also used. PMID- 17271412 TI - A generic input device for the multiple master multiple slave system. AB - The growing demand for input devices designed for the severely handicapped led to development of modular features for the open architecture multiple master multiple slave (M3S) system. With its central safety monitor, M3S allows individuals suffering from cerebral palsy, paraplegia, or multiple sclerosis, and other physically debilitating illnesses greater autonomy by allowing them to access a wide range of input devices tailored to a specific user, e.g., joysticks, keypads, head-control modules and speech recognizers. These input devices, which are equipped with basic configuration abilities, are operated with DSP cores and additional circuitries to maintain optimal control and high levels of safety, and may be modified or expanded with minimal adjustments. PMID- 17271413 TI - Diagnosis and rehabilitation of patients with hemispatial neglect using virtual reality technology. AB - Our objective is to develop and test a system for diagnosis and rehabilitation of patients with hemispatial neglect. The system consists of a 3D-haptic virtual world seen through stereo shutter-glasses. Patients interact by manipulating a haptic interface. The software adapts the virtual world accordingly to haptic interface and eye tracking feedback. Offline analysis is possible by reviewing recorded data. Observations made during experimentations with hemiplegics patients and future works with hemispatial neglect patients are discussed. PMID- 17271414 TI - Development of the walking support robot with the weight bearing mechanism supporting ischia--cushion for ischia and behavior of ischia during walking. AB - This report describes the cushion suitable for weight bearing mechanism supporting ischia and the behavior of ischia during walking. Hitachi Ltd. developed the power-assisted walking support device and the walk training machine with weight bearing mechanisms using a hip orthosis and a saddle. Because user's weight is centered on symphysis pubica, users feel sore and it is obstacle to smooth walking. Then, we propose a new weight bearing mechanism supporting ischia. Because an interface between human and robot is important, we experimented on the cushion for ischia that is the interface between human and the weight bearing mechanism supporting ischia. In the experiment, we measured seating pressure, the trajectory of the seating pressure's center, position of ischia, and force on the weight bearing arm when a user was walking while locating his hip on the cushion for ischia. The result shows that the seating cushion is suited for the interface, but it is also necessary to support separately each ischium's up down movement and rotating movement during walking. PMID- 17271415 TI - Quantification of reaching during stroke rehabilitation using unique upper extremity kinematic model. AB - Quantification of rehabilitation progress is necessary for accurately assessing clinical treatments. A three-dimensional (3D) biomechanical model of the upper extremity was developed for quantification of stroke rehabilitation. The model was designed to accurately track the 3D orientation of the trunk, shoulder, elbow and wrist. This study explains the application of the upper extremity model. Strict validation of the model confirmed the system's accuracy and resolution. The model was applied to eight hemiparetic stroke patients with spasticity, while completing a set of reaching tasks. The model successfully detected statistical differences in elbow range of motion and angular velocity between the nonparetic (unaffected) and paretic (affected) arms. Both simple and complex biomechanical indices for assessment were developed. This model may aid in the assessment and planning of stroke rehabilitation, and help to decrease recovery time. PMID- 17271416 TI - A mobile tool for accessibility and usability testing of medical instrumentation. AB - The Mobile Usability Lab (MU-Lab) is a tool developed by the Rehabilitation Engineering Research Center on Accessible Medical Instrumentation (RERC-AMI) to study the accessibility and usability of medical devices by people with diverse abilities. The system includes a suite of data collection hardware components and a custom software interface to help coordinate problem identification and planning as well as data collection and analysis for usability and accessibility research of medical devices. Hardware components include a laptop computer, data acquisition card, video cameras, quad video processor and wireless microphones. Software components include a customized Web-based usability suite, real-time data collection package and several video editing and data analysis tools. PMID- 17271417 TI - Analysis of impulse response on walking stability using accelerometers. AB - The walking stability becomes less stable under the influence of a problematic posture or back. This problem was analyzed on the basis of two new approaches. The first approach is a newly developed measurement system, consisting of two accelerometers for walking analysis. It was a small, wearable, micro PC-assisted portable system. However, it was difficult to analyze directly the characteristics of movement stability using the raw measurement data. The second approach was an analysis of impulse response using AR modeling. Once it was understood standing with correct posture, the fluctuation of subject's both sides of the hip while walking was improved more rhythmic in the female students. The analysis of impulse response, utilizing AR modeling, provided clear results for the evaluation of improvement to walking stability. PMID- 17271418 TI - The mechanomyogram as a channel of communication and control for the disabled. AB - This paper describes an original system to provide a communication and control tool for people who are disabled. The mechanomyogram (MMG) is used as a control signal to operate an alphabet board. The MMG is the mechanical signal observable at the surface of a muscle due to vibration of the motor units underneath. Contraction of the muscle increases the amplitude of the vibrations. The system described detects the MMG from either the biceps brachii or the sternocleidomastoid muscle using a dual-axis accelerometer. The signal is read into the computer and processed. A decision is made as to whether the muscle is contracted or relaxed based on the amplitude of the processed signal. If the computer decides that the muscle is contracted, a software switching action is performed. This switching action is used to control a software alphabet board which the disabled person can use to spell out messages. PMID- 17271420 TI - A virtual reality based exercise system for hand rehabilitation post-stroke: transfer to function. AB - We present preliminary results from a virtual reality (VR)-based system for hand rehabilitation that uses a CyberGlove and a Rutgers Master II-ND haptic glove. This system trains finger range of motion, finger flexion speed, independence of finger motion and finger strength. Eight chronic post-stroke subjects participated. In keeping with variability in both the lesion site and in initial upper extremity function, each subject showed improvement on a unique combination of movement parameters in VR training. These improvements transferred to gains on clinical tests, as well as to significant reductions in task completion times for the prehension of real objects. These results are indicative of the potential feasibility of this exercise system for rehabilitation in patients with hand dysfunction resulting from neurological impairment. PMID- 17271419 TI - Enhanced TheraJoy technology for use in upper-extremity stroke rehabilitation. AB - Due to rising costs of health care and decreasing length of conventional therapy, it has become imperative to develop affordable, motivating devices that can be used in the home for upper-extremity stroke rehabilitation. In the TheraJoy project, a commercial joystick has been modified to enlarge the range of arm movement used during therapeutic movement tasks, and to support the application of light passive and actuated forces. The enhanced version presented here allows for motion in both the horizontal and vertical planes, uses a dynamic linkage model to map joystick-hand position and force data, uses motivating gaming technology, and can be used in both therapy and in home settings. This study compares performance and benefits of motion in the horizontal to vertical plane, evaluates user performance during assessment and therapy tasks, and documents user opinions of potential uses of this technology for stroke rehabilitation. PMID- 17271421 TI - A text input system developed by using lips image recognition based LabVIEW for the seriously disabled. AB - In this paper, we present a text input system for the seriously disabled by using lips image recognition based on LabVIEW. This system can be divided into the software subsystem and the hardware subsystem. In the software subsystem, we adopted the technique of image processing to recognize the status of mouth-opened or mouth-closed depending the relative distance between the upper lip and the lower lip. In the hardware subsystem, parallel port built in PC is used to transmit the recognized result of mouth status to the Morse-code text input system. Integrating the software subsystem with the hardware subsystem, we implement a text input system by using lips image recognition programmed in LabVIEW language. We hope the system can help the seriously disabled to communicate with normal people more easily. PMID- 17271422 TI - Three-dimensional dynamical measurement of upper limb support during paraplegic walking. AB - Functional electrical stimulation (FES) has been employed in paraplegic rehabilitation to resume their walking ability. However, there is less quantitative assessment method of FES walking efficiency and rehabilitation progress. This paper presents a new dynamical measurement of upper limb support force during paraplegic walking, which can be used to calculate the 3-D handle reaction vector (HRV). HRV may provide an assessment of FES-assisted efficiency. With a series of tests, the measurement accuracy, nonlinearity, and crosstalk of the designed system are testified. The force measurement error is found below 1.01%, while nonlinearity and crosstalk are less than 2.90%, and 3.19%, respectively. This means that the implemented walker system is reliable for the measurement of HRV during FES-assisted walking. A clinical trial is performed with a paraplegic subject. With the monitoring of FES-assisted walking, the downward component of HRV is found to decrease, implying the decreasing force generated from lower limb. The decrease slope in downward load curve can indirectly indicate the FES efficiency change during walking. The experiment and clinical trial results show that a 3-D dynamical measurement system is successfully accomplished to indirectly assess FES efficiency of lower limbs using quantitated forces applied by the upper limbs of paraplegic patients. PMID- 17271423 TI - Sensory substitution system of two-channel electrotactile stimulation for transmitting verbal information. AB - We have aimed at developing a sensory substitution system for transmitting verbal information. In this work, we propose a basic two-channel electrotactile stimulation system and examine the usefulness of the system. The verbal information to be provided consists of two items: one is the object and another is the location (direction) of the object in the surrounding of the subject Three objects and three directions are utilized in this work. Each of the nine possibilities was transmitted to the subject as a skin stimulus consisting of two consecutive stimulation patterns; the first pattern represents the direction and the second the object. Stimulation pattern for each item was generated by two channel voltage-pulse trains, which elicited a movement impression on the subject's skin. The electrical stimulus was delivered on the dorsal carpal area of the left hand. High percentage of recognition (average: 92%, standard deviation: 4.2) was obtained. Recognition percentages were improved by giving the subject a prior explanation about each stimulation pattern and increasing the stimulus intensity up to 95 % of the pain threshold. PMID- 17271424 TI - Development of the assist system to operate a computer for the disabled using multichannel surface EMG. AB - The purpose of this study is development of the assist system to easily operate a computer for the disabled such as amputees. In order to operate a computer, we usually use a mouse, and our system assists a mouse operation. Our system requires electromyography (EMG) signals of the arm instead of the mouse operation by the hand, and those EMG signals are used to become a control source for the mouse operation. To acquire the EMG signal, using a multichannel electrode that has 96 channels is a key of this assist system. As for the old assist system using the EMG, most of them require the definition of the target muscle. In many cases, these systems used 2 or more electrodes. We have developed an assist system using 96 channels matrix-type surface multi channel electrode. The EMG signal is recognized by canonical discriminant analysis. From measured EMG data, we can discriminate 10 movements of the hand. So, our system will be a powerful one to support activities of the disabled. PMID- 17271425 TI - Development of automatic immediate fitting socket system for artificial leg socket modeling using fuzzy control. AB - Automatic immediate fitting socket (AIFS) system was developed to shorten the long length of time for making an artificial leg, by applying powder technology. AIFS is constructed of an outer shell, a particle containing bag, which the rigidity can be controlled by the application of negative air pressure and three airbags between the outer shell and the particle bag to adjust the shape by controlling the compression. A fuzzy controller was applied for the real-time automatic control of the shape based on the subjective evaluation of the amputee. The surface contact pressure was evaluated during AIFS walking as well as the walking with the conventional socket. The peak pressure at the tibia end was 30 kPa in AIFS walking while 90 kPa with conventional socket. The pressure distribution among medial condyle, fibula head and tibia end was more uniform with AIFS. The shape modeling performance was evaluated by measuring the circumferences of four amputees' stumps. The modeling error was 6%. The shape modeling including test walking was completed in 10 minutes in all four amputees and practical shapes were obtained. PMID- 17271426 TI - Development of a piezoelectric actuator for presentation of various tactile stimulation patterns to fingerpad skin. AB - In order to investigate tactile perception characteristics of the human fingerpad for the optimal design of a sensory substitution system, we have developed a small piezoelectric bimorph actuator that possesses flat frequency characteristics in the vibratory frequency of tactilely perceivable bandwidth. The parameters for the design of the bimorph were determined by using a mechanical simulation model of a piezoelectric bimorph and a fingerpad skin. To evaluate the performance of the bimorph, we measured frequency-displacement relationships when the skin of a fingerpad was vibrated by the piezoelectric bimorph. The experimental results showed that the frequency-displacement relationships were almost the same as the estimation obtained from the mechanical simulation model. PMID- 17271427 TI - Using microenvironment to engineer stem cell function. AB - Stem cells differentiate into different lineages depending on the local cues present in their microenvironment. While soluble cues have been studied in great depth, little is known about the role of insoluble cues such as cell adhesion and mechanical forces. We now show that human mesenchymal stem cells (MSCs) commit to different lineages depending on their physical microenvironment. Using microfabricated tools, we found that cell shape regulates MSCs commitment, and does so through a cytoskeletal tension-dependent pathway. We will discuss the novel tools that we are developing to study these mechanical signals, and how they have informed us about how cells probe and respond to their environment. PMID- 17271428 TI - Quantitative analysis of signaling mechanisms controlling adult neural progenitor cell proliferation. AB - Tools of systems engineering and signal dynamics were employed to develop a quantitative model of the intracellular signaling systems involved in adult neural stem cell proliferation, based on pathways elucidated in our experimental systems. Neural progenitors isolated from the adult rat hippocampus are dependent on the basic fibroblast growth factor (FGF-2) and extracellular matrix (ECM) proteins. However, the intracellular effects of these stimuli were previously undetermined. We employed chemical inhibitors of known signal transduction molecules to identify important players in the FGF-2/ECM signal cascade, such as the cyclic AMP responsive element binding protein (CREB), protein kinase B/Akt, and several related molecules. Genetic mutants of these proteins were used to confirm their role in adult neural progenitor proliferation. Proliferation was assayed using the incorporation of a thymidine analog to determine cell doubling rate under various stimuli. Such assays have also uncovered novel synergistic signaling between FGF-2 and ECM components. This research is, to our knowledge, the first to elucidate intracellular signaling pathways for adult neural stem cell proliferation. Upon determination of the pertinent intracellular signaling pathways, quantitative immunoblots were employed to examine the dynamics of these systems. These data, as well as enzyme kinetics information from the literature, are being used to parameterize a dynamic mathematical model of progenitor proliferation events induced by FGF-2. This computational model will be used to predict the biochemical and mechanical signaling inputs necessary to achieve a desired proliferative output from the cells, based on specific extracellular stimuli. It is our hope that this essential quantitative understanding will facilitate the use of adult neural stem cells in medical applications. PMID- 17271429 TI - Tissue engineering of muscle on micropatterned polymer films. AB - Tissue engineered skeletal muscle has potential physiologically relevant environments to study myogenesis and investigate the organization, differentiation and proliferation to be used for the therapy of muscular dysfunction. In order to engineer skeletal muscle that better resemble the structured architecture in vivo, we cultured myoblasts on topographically micropatterned elastic polymer films with 10-mum wide microgrooves. The organization and differentiation of myoblasts on nonpatterned and micropatterned PDMS films were characterized. In comparison to the myoblasts on nonpatterned PDMS films, myoblasts on micropatterned PDMS films aligned themselves along the direction of the microgrooves. The myoblasts on micropatterned films formed long and unbranched myotubes that had uniform diameter and aligned in the microgroove direction, suggesting that microgrooves promote end-to end fusion of myoblasts; in contrast, myotubes formed on nonpatterned surface were short and less uniform in diameter, and oriented in various directions. This study demonstrates a new approach to engineer muscular tissues on flexible substrate, and highlights the importance of topographical cues for creating more engineer skeletal muscle. PMID- 17271430 TI - The topographical guidance of neurons cultured on holographic photo-responsive polymer. AB - Neuronal cells to respond to submicron-scale groove structure. On the grooved structure of particular dimension, it has been reported that neuronal cells grew perpendicular to the groove direction. We used holographic photo-responsive polymer to form a submicron-scale surface relief grating structure. A sinusoidal groove pattern is built up by holographic interference of 488 nm Ar ion laser beams. The primary hippocampal neurons cultured on the surface of the polymer film grew extending their neurites in a perpendicular orientation to the groove direction. This suggests that laser holography can be used to control the neurites orientation and growth. The holographic grating and photo-responsive polymer will raise the possibility of controlling neural network formation between living cells by light. PMID- 17271431 TI - Kinetics of LFA-1 binding to ICAM-1 studied in a cell-free system. AB - Neutrophil capture on inflamed endothelium is controlled by dynamic regulation of the integrin CD11a/CD18 (LFA-1). Small molecules, antibodies, and certain divalent cations binding to specific epitopes on the integrin are able to stabilize either a closed (low affinity) or open (high affinity) state. To determine the relationship between LFA-1 conformation and affinity for ICAM-1 we assembled a cell-free system consisting of CD11a/CD18 heterodimer adhered to latex microspheres. The kinetics of dimeric ICAM-1 binding to the LFA-1 on the microspheres was measured via flow cytometry and a real time conformational shift into a lower affinity state was observed by addition of a small molecule inhibitor. PMID- 17271432 TI - Simulating leukocyte-venule interactions--a novel agent-oriented approach. AB - Leukocyte recruitment into sites of inflammation involves a complex cascade of molecular interactions between the leukocyte and the endothelial cells of the inflamed venule. This report proposes a novel agent-oriented approach for simulating leukocyte-venule interactions during inflammation. We focus on modeling and simulating the initial steps of rolling, activation, and firm adhesion of neutrophils on TNF-alpha-treated mouse cremaster muscle venules. PMID- 17271433 TI - Polarization-modulated second harmonic generation imaging: method for quantitative assessment of disorganization in anulus. AB - An experimental method for quantifying disorder within the anulus fibrosus is described based on polarization-modulated second harmonic generation imaging (PM SHG-I). This method is demonstrated by imaging the anular lamellar architecture of a mouse model of compressive loading. Results were consistent with those obtained in an earlier study where organization was quantified directed secants image analysis on photomicrographs. In this study the orientation within individual lamellia is quantified by average orientation of the collagen molecules within a defined volume of a single lamellar as measured by the PM-SHG I. Lamellar boundaries can be identified through the SHG intensity images, and confirmed through co-registration with photomicrographs of the same region. The orientation within the lamellar is quantified by the polarization angle of the maximum second harmonic intensity. PM-SHG-I offers several advantages as compared with the method of directed secants: first, it is nondestructive, allowing repeated measurements of the same tissue; second, images are captured on the order of seconds and capable of obtaining information up to a depth of 200-300 microns, thus allowing for real-time assessment of load damage; third, organization is measured at a much higher resolution, as it is based on disorder within the molecular arrays of a single lamella. PMID- 17271434 TI - Spectroscopic studies of mitochondrial NADH fluorescence signals in brain slices. AB - Dysfunction of mitochondria links a variety of central nervous system (CNS) disorders and other neurodegenerative diseases. The primary respiratory chain substrate reduced form nicotinamide adenine dinucleotide (NADH) is an important regulator of respiratory chain function in mitochondria and, because of its fluorescent properties, has been used to assess mitochondrial pathophysiology in cells and tissues. However, assessment of changes in tissue NADH has been limited to qualitative analysis primarily because hemoglobin (Hb) interferes with NADH fluorescence measurements by absorbing both excitation and emission light. This study presents a computer-assisted approach to estimate brain tissue NADH and Hb concentrations quantitatively at the same time. The method is based on a two dimensionally interpolated database model that is calibrated by fluorescence emission spectra with known-value standard chemical solutions. Quantitative concentrations for NADH and Hb can be determined by the corresponding known-value spectral data that have the minimum error to the sample spectrum obtained from an experiment. Repeatability and reliability tests are also presented in this report. Results demonstrate that this method can feasibly quantify the NADH content regardless of the Hb background in living hippocampal cells during hypoxia, suggesting that it has potential to be applied to in vivo experiments in the future. PMID- 17271435 TI - Study of the effects of 50 Hz homogeneous magnetic field on apoptosis and proliferation of SNU cells in vitro. AB - The biological effects of magnetic field on SNU (human low differentiated gastric adenocarcinoma cell line) cells are studied in this paper. SNU cells were randomly divided into control groups and four treatment groups, the treatment groups were respectively irradiated by 50 Hz ferromagnetic field (0.097 T) 5 min., 30 min., 60 min., and 120 min. We observed the effects on proliferation and apoptosis of SNU cells after the treatment of magnetic field by flow cytometric (FCM) DNA analysis and electron microscope observation. The apoptosis rate in treatment groups are 4.75% +/- 1.24%, 6.50% +/- 0.61%, 9.20% +/- 1.76% and 6.26% +/- 2.95% respectively and significantly higher than that in control group. In the irradiation time range from 5 min to 60 min, there is a significant time depended response correlation of apoptosis rate( r = 0.97, P < 0.01), but FCM results showed that the effects of 50 Hz homogeneous ferromagnetic field on the proliferation and distribution of cell cycle of SNU cells is not significant. We concluded that irradiation of 50 Hz homogeneous ferromagnetic field could promote apoptosis of SNU cells. PMID- 17271436 TI - Inactivation of atmospheric bacteria using lytic enzyme mixture. AB - The mass of air breathed by a human per day is equivalent to 10-times the mass of food consumed in that time. However, fundamental safety measures for atmospheric bacterial control have not yet been implemented. The purpose of our research is to develop a cell wall Iytic filter using a cell wall Iytic enzyme, which can inactivate the bacteria in air that cause infectious diseases by decomposing their cell envelope. In this study, the use of Iytic enzyme mixture was suggested, including glycosidase, protease and lipase. The performance of the Iytic enzyme mixture was evaluated using lysozyme, a typical Iytic enzyme, as a control. The substrate that we used was Micrococcus luteus, a gram-positive bacteria. The experimental results showed that the use of the Iytic enzyme mixture exhibited a Iytic rate per hour that was 13 - 39% greater than the control. Furthermore, although there are some different phases during bacterium multiplication, the Iytic rate per hour improved for all of the phases when the Iytic enzyme mixture was used. PMID- 17271437 TI - Challenges in capillary pressure microinjection. AB - Capillary pressure microinjection is a popular method for the delivery of samples into cells. Needs for automatic reliable microinjection systems are growing, but the current systems do not possess ideal characteristics and many researchers do not even recognize the limits of the current systems. In many cases for example, the experiments are influenced by so called influx or efflux. This paper discusses the limits and challenges related to the automatic microinjection of single adherent cells. The discussion focuses on the reasons for the variability of the injected volume and shows the complexity of the problem. Solutions are outlined and future steps sketched. Future developments in the field of microinjection are proposed. PMID- 17271438 TI - Development of a computational model for cellular pacemaking of gastrointestinal system. AB - Results from recent experiments undertaken on tissue from the gastrointestinal (GI) tract suggests that the interstitial cells of cajal (ICC) are the pacemaker cells responsible for slow wave propagation. The pace-making mechanism of ICC networks is strongly dependant on intracellular spatial dynamics of Ca/sup 2+/. A modeling framework has being developed to test the hypothesis of voltage dependant Ca channels being responsible for the pace-making mechanism of ICC. The model consists of a coupled system of ordinary differential equations. Regional calcium conservation equations were applied to intra-cellular pools within the ICC framework. Future work with the model will fit parameters from experimental data. This model will also be used to form the basis of a GI tract slow wave computational model. PMID- 17271439 TI - Lethal and inhibitory effects of steep pulsed electric field on tumor-bearing BALB/c mice. AB - Exposing cancer cell to steep pulsed electric field (SPEF) with appropriate dosage, the cell may die due to irreversible electrical breakdown (IREB). 48 BALB/c mice inoculated with U/sub 14/ cervical cancer cell were treated with SPEF to study the lethal and inhibitory effects of SPEF on them. They were randomly divided into test group (26) and control group (22), and then four experiments were carried out. Histological observation and ultrastructural observation showed that SPEF destroyed the integrality of tumor cell irreversibly with pyknosis, karyoclasis and karyolysis. Tumor volume measurement indicated that SPEF significantly slowed down the growth speed of tumor. In the experiment of survival time investigation, the average survival time of control group and test group was 33.03 days and no less than 52.05 days respectively, which confirmed that SPEF prolonged the survival time of tumor-bearing mice obviously. With further experimental study and mechanism analysis, this technique is quite possible to be an effective physiotherapy for tumor treatment. PMID- 17271440 TI - Vascular effect and immunity effect of steep pulse electric field on Walker 256 bearing Wistar mice. AB - The vascular effect and immunity effect of SPEF on Wistar mice were studied, and the possible treatment mechanisms and clinical trial methods of SPEF were discussed. We tested lymphocyte proliferation ratio and activity of NK cell, and the contents of IFN-alpha and IL-4 in the serum lymphocyte were inspected with ELISA method. Moreover, macrophage were collected, the content of TNF-alpha excreted by macrophage were inspected with ELISA method, too. Statistical analysis was performed using the SPSS10.0 software package and t-test. VEGF level in test group was significantly decreased, and VEGF expression was weakened evidently. SPEF strengthened activity of NK cell, enlarged quantities of TNF alpha from test group, accelerated exudation of TH1 cell factor and slowed exudation of TH2 cell factor. SPEF showed effective anti-tumor effect through restraining the formation of fresh vessels and baffling the birth and transfer of tumor cell. It could strengthen organism immunity function, and had visible effect on Walker-256 tumor. PMID- 17271441 TI - Long-term stability of plasma oxidized PDMS surfaces. AB - The hydrophilicity of untreated polydimethylsiloxane (PDMS) surfaces is problematic in applications where adhesion of proteins and cells is desirable. In this work, we investigated the effects of variables involved with plasma surface oxidation including time, power, monomer extraction, and storage conditions over 45 days. In order to maintain a hydrophilic surface for the longest time, the storage condition was the most influential factor above all other variables. Investigated changes in plasma treatment time, and power had less profound effects. Furthermore, only marginal differences in extracted and non-extracted PDMS were observed. PMID- 17271442 TI - Multiple volume injection technique for high-resolution DNA sample detection utilizing planar microfluidic chip. AB - This paper presents an experimental and numerical investigation into the use of high-resolution injection techniques to separate DNA fragments within electrophoresis microchips. The study addresses the principal material transport mechanisms such as electrokinetic migration, fluid flow, diffusion, variable volume injection methods, and gives detail analyses to the double-L injection technique, which employs electrokinetic manipulations to avoid sample leakage within the microchip. We also study the sample leakage effect during sample injection and separation. The standard DNA ladder and the phi/-174 DNA fragments are used to test the performance for this proposed method. Results show that this unique injection system in the current microfluidic chip presented within this paper is capable of simulating the functions of the cross, double-T form through appropriate manipulations of the electric field within its various channels. The proposed double-L injection method confirms its ability to reduce sample leakage effect during operation. The integrated microfluidic chip and double-L injection technique developed in this study has an exciting potential for use in high quality, high-throughput chemical analysis applications and in many other applications throughout the field of micro-total-analysis systems. PMID- 17271443 TI - Biomimetic scaffolds for tissue engineering. AB - A major goal of tissue engineering is to generate living cellular constructs with 3-D, tissue-like organization of cells and matrices. The generation of mechanical forces by the cellular cytoskeleton plays a critical role in the organization of matrix and of cellular colonies. The anchorage of the cytoskeleton to a substrate is essential for cellular tractional processes. We show that placing cells in scaffolds which contain a collagen-related synthetic peptide P-15 allows them to generate highly organized 3-D colonies and matrices. These observations suggest that P-15 may replicate cells' physiological collagen anchorage. PMID- 17271444 TI - Mechanical regulation of matrix reorganization and phenotype of smooth muscle cells and mesenchymal stem cells in 3D matrix. AB - In an effort to develop small-diameter tissue-engineered vascular grafts (< 6 mm), collagen and fibrin gels seeded with human aortic smooth muscle cells (HASMCs) were constructed in a three-dimensional tubular environment and subjected to mechanical stimulation to investigate changes in cellular response and matrix remodeling. After testing various collagen and fibrin concentrations, experiments indicated 2:1 mg/mL of collagen:fibrin constructs with embedded HASMCs contracted as well as the pure fibrin, at 54% their original length after 3 days, indicating enhanced cellular activity and matrix remodeling . Vascular constructs were cultured for three days before undergoing pulsatile 10% cyclic strain at 1 Hz for three days. RT-PCR showed that cyclic strain increased the gene expression of SMC markers alpha-actin and SM22, indicating that mechanical stimulation induces SMCs to a more contractile phenotype. Histology showed a more compacted collagen fiber structure for mechanically stimulated constructs compared to the looser collagen network in static constructs. The effects of 3D mechanical strain were also tested on mesenchymal stem cells (MSCs), which can be a possible source for SMCs. Cyclic strain increased alpha-actin and SM22 gene expression in MSCs, suggesting the differentiation of MSCs into a SMC phenotype. PMID- 17271445 TI - Synthetic peptides cytomodulin-1 (CM-1) and cytomodulin-2 (CM-2) promote collagen synthesis and wound healing in vitro. AB - Transforming growth factor-beta1 (TGF-beta1) is believed to be a key player in wound healing, promoting cell proliferation, migration, and matrix synthesis in a variety of cell types. We have designed two peptides, i.e., cytomodulin-1 (CM-1) and cytomodulin-2 (CM-2), to simulate the binding domain of TGF-beta1. In this study we examined the bioactivity of the two synthetic peptides CM-1 and CM-2 on human foreskin fibroblasts (HFF). Synthetic peptides CM-1 and CM-2 in culture media increased wound healing of fibroblasts in an injury model in vitro. In addition, CM-1 and CM-2 enhanced the gene expression of collagen I and increased the production of pro-collagen I peptide in HFF. These results suggest that CM-1 and CM-2 have potentially useful clinical applications in wound healing. PMID- 17271446 TI - The necessity of a theory of biology for tissue engineering: metabolism-repair systems. AB - Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering. PMID- 17271447 TI - Control of cell function with tunable hydrogel networks. AB - A critical problem limiting the field of tissue engineering is the lack of engineering design rules to guide the synthesis and fabrication of artificial extracellular matrices (ECMs) or scaffolds. To address this issue, we have created artificial ECMs that are environmentally responsive and tunable with respect to mechanical properties (e.g. G*), biological ligands, tissue adhesion, and protease degradation. Our current approach is to create modular hydrogel ECMs where different properties of the matrix can be manipulated independently, thus creating a system where parametric analysis of the effect of hydrogel properties on cell proliferation and differentiation is possible. For example, we have synthesized and characterized the physical properties of semi-interpenetrating polymer networks (sIPNs) consisting of linear polyacrylic acid (pAAc) chains within a thermo-responsive N-isopropylacrylamide-co-acrylic acid network [p(NIPAAm-co-AAc)]. Studies addressing the effect of RGD ligand type and density, in the context of matrices with various mechanical properties, have indicated that G*, RGD density, and protease cross-linkers are critical for rat calvarial osteoblast adhesion and proliferation. These peptide-modified P(NIPAAm-CO-AAc) hydrogels allow for easy control of the mechanical and chemical properties of the matrix, allowing parametric analysis of the effect of these properties on cell behavior in vitro and tissue development in vivo. PMID- 17271448 TI - Molecularly engineered hydrogels for implant biocompatibility. AB - The biocompatibility of biosmart polymer membranes synthesized from cross linkable (2-hydroxyethyl methacrylate) (HEMA) and tetraethylene glycol diacrylate and containing different mole-percent polyethylene glycol methacrylate (PEGMA) and methacryloyloxyethyl phosphorylcholine (MPC), a phosphorylcholine-containing co-monomer, was investigated. The cytotoxicity (cell viability and proliferation) and the adhesion of extra cellular matrix proteins to these hydrogel surfaces were separately tested. Cell proliferation assays were conducted by cultivating human skeletal muscle fibroblasts onto the surfaces of these polymeric membranes prepared by in-situ polymerization in chemically derivatized 8-well cell-culture plates. The compositions containing MPC and PEGMA concentrations greater than 1.0 and 0.05 mole% respectively demonstrated good protein adhesion and cell viability (>90%) of human muscle fibroblast cells. Morphological deviances and partial colonization of the hydrogel surface has been noticed and suggests good compatibility of hydrogels for cellular viability but restricted proliferation. It is well known that the adsorption of proteins onto biomaterial surfaces modulates the cellular interaction with these surfaces. The extent of adsorption of fluorescein labeled proteins (laminin, collagen, and fibronectin) onto these polymer membrane surfaces was evaluated by measuring the resultant fluorescence intensity using a confocal fluorescence scanner. PMID- 17271449 TI - Endothelial cell function on a poly(acrylamide-co-polyethylene acid) interpenetrating polymer network: cardiovascular applications. AB - Hydrogel coatings have been widely researched as a nonfouling surface modification of materials for cardiovascular applications. In this study, we examined cell-surface interactions between a poly(acrylamide-copolyethylene glycol/acrylic acid) interpenetrating network (IPN) hydrogel and aortic endothelial cells (ECs). The IPN was covalently attached to polystyrene to form a nanometer scale thick hydrogel, and the IPN layer was activated by conjugation of the cell adhesion peptide Arg-Gly-Asp (RGD). On IPN surfaces lacking the RGD peptide, EC did not adhere and spread even after long-term incubation. The IPN was able to support greater EC adhesion and spreading with increasing RGD surface concentrations. Upon adequate adhesion and spreading, ECs migrated and proliferated at high rates regardless of the RGD surface concentration. These results suggest that this IPN can be used to promote endothelialization of vascular implants made of polymeric and metal materials for cardiovascular applications. PMID- 17271450 TI - The attachment, proliferation, and wound healing of endothelial and smooth muscle cells on nitinol thin film in vitro. AB - Nitinol (TiNi) thin film is a potentially useful material for various clinical applications, e.g., vascular stents. In this study we examined the biological functions of bovine endothelial cell (BAEC) and bovine smooth muscle cells (BSMC) on 1-mum thick amorphous TiNi films. BAEC and BSMC both attached on TiNi film, and exhibited increased cell spreading in the presence of serum containing media. Both cell types had decreased cell proliferation on TiNi as compared to glass control; however, BAEC had significantly greater proliferation rate than BSMC on TiNi. In an in vitro wound model, BSMC migrated faster than BAEC, resulting in a quicker closure of the monolayer. These results provide important insights into the interactions of vascular cells and TiNi thin film, and will help us to optimize the surface properties of TiNi film for applications in the vascular system. PMID- 17271451 TI - A drug delivery system for the treatment of peripheral nervous system injuries. AB - Recent results in biomedical engineering and materials science and technology have brought about the development of novel bioactive materials by which the repair of peripheral nervous system injuries can be improved. The formation of scarring tissue, which represents a physical barrier to axon elongation, and the not oriented outgrowth of neurites are the two major obstacles for a complete recovery of physiological nerve function. This study mainly focuses on the analysis of biocompatible constructs for the controlled release of anti-scarring antibodies by means of fluorescence spectroscopy techniques. PMID- 17271452 TI - Mechanical properties of bone-implant interface: an in vitro model for the comparison of stability parameters affecting various stages during osseointegration for dental implant. AB - Radiographic examination and palpation have been two of most common the methods often used in clinical assessment for implant stability for years. However, radiographs are two-dimensional and difficult to standardize in dental clinical diagnosis. In current study, an in vitro model for dental implant during osseointegration was designed and tested. To attain optimal healing range prior to frequency measurement, removal torque measurements of the initial as well as plateau mechanical bounding force will be exam for various stiffness of the base materials. Resonance frequency measurements will then be taken at predetermined healing intervals on implants placed in experimental animal. Significance between mechanical stability and increase in resonance frequency will be observed in search of its correlation with the stability of the implant-tissue interface. PMID- 17271453 TI - Cyclic stretch increases VEGF expression in pulmonary arterial smooth muscle cells via TGF-1 and reactive oxygen species: a requirement for NAD(P)H oxidase. AB - We have previously shown that TGF-1 and VEGF expression are increased in the smooth muscle cell (SMC) layer of the pulmonary vessels of lambs with pulmonary hypertension secondary to increased pulmonary blood flow. Further we found that TGF-1 expression increased prior to VEGF. Due to the increased blood flow in these lambs the SMC in the pulmonary vessels are exposed to increased levels of cyclic stretch. Thus, using primary cultures of pulmonary arterial SMCs (PASMCs) isolated from 4 week-old lambs, we investigated the role of cyclic stretch in the apparent coordinated regulation of TGF-1 and VEGF. Our results demonstrated that cyclic stretch induced a significant increase in VEGF expression both at the mRNA and protein preceded by an increase in expression and secretion of TGF-1 and an increase in reactive oxygen species (ROS) generation. In addition, a neutralizing TGF-1 antibody abolished the cyclic stretch-dependent increase in ROS and VEGF expression. Further, we found that cyclic stretch activated an NAD(P)H oxidase in a TGF-1 dependent manner that when inhibited abolished the cyclic stretch dependent increase in VEGF expression. Our results indicate that cyclic stretch up-regulates VEGF expression via the TGF-1 dependent activation of NAD(P)H oxidase and increased generation of ROS. PMID- 17271454 TI - Sickle cell blood flow in the microcirculation. AB - The clinical symptomology, as well as the subclinical sequela, of sickle-cell (S C) disease, or anemia, is thought to be largely the consequence of abnormal events in the capillaries, resulting primarily from theological changes SC erythrocytes undergo when deoxygenated. A model of the flow of such RBCs in a single capillary was formulated taking into account the principal characteristics of the disease. This has been extended to a microcirculatory bed, generated in a pseudo-random manner. S-C disease is characterized by episodic painful and debilitating clinical events, called S-C "crisis". These studies, undertaken to evaluate possible causative mechanisms, suggest that the pressure available to drive the S-C RBCs through the microcirculation might be the control parameter. PMID- 17271455 TI - Mechanical property characterization of the zebrafish embryo chorion. AB - A microrobotic force sensing system is used to characterize the mechanical properties of the chorion of zebrafish embryos and quantitate the mechanical property differences of the chorion at different developmental stages. Quantitative relationships between applied forces and chorion structural deformations are established for various developmental stages. The measured penetration forces for puncturing chorion at the blastula stage are 1.3 times as large as those at the pre-hatching stage. Through the use of an analytical biomembrane elastic model, chorion elastic modulus values are determined. The modulus at the blastula stage is 1.66 times as large as that at the pre-hatching stage. The experimental results quantitatively describe "chorion softening," which is mostly due to the proteolytic activity at the pre-hatching stage. This study also reveals the effect of pronase treatment on zebrafish chorion, which produces an "artificial chorion softening" effect. This draws an analogy between pronase treatment and proteolytic activities at the pre-hatching stage. PMID- 17271456 TI - Modulation of ATP/ADP concentration at the endothelial surface by shear stress: effect of flow disturbance. AB - The adenine nucleotides ATP and ADP modulate the release of endothelial-derived relaxing factors and hence play an important role in flow-mediated arterial vasoregulation. Adenine nucleotide concentration at the endothelial cell (EC) surface within an artery is determined by a balance of convective-diffusive delivery of blood-borne nucleotides to the EC surface, hydrolysis of these nucleotides at the cell surface, and flow-induced ATP release from ECs. Previous numerical simulations in a parallel plate flow chamber had demonstrated that flow induced ATP release has a profound effect on nucleotide concentration under both steady and pulsatile flow conditions. In the present study, we have extended this analysis to probe the impact of disturbed flow downstream of a backward facing step on adenine nucleotide concentration at the EC surface. The results have demonstrated that over a wide range of applied wall shear stress, the ATP concentration at the EC surface drops abruptly within the disturbed flow zone due to increased nucleotide residence time within this region. The concentration is intricately sensitive to the kinetics of flow-induced ATP release, and this sensitivity is more pronounced at lower levels of wall shear stress. PMID- 17271457 TI - Dynamic deformation capability of a red blood cell under a cyclically reciprocating shear stress. AB - Red blood cells (RBCs) in the cardiovascular devices are exposed to varying degree of the shear stress from all the directions. However the RBCs' deformability or the deformation capability under such a shear stress is not well understood. In this study, we designed and built a system that can induce a cyclically reciprocating shear stress to a RBC suspension. The arm of the cyclically reciprocating shear stress device was attached to the upper piece of the parallel glass plates between which a suspension of human RBCs (1% hematocrit whole blood diluted in a 32 weight% dextran phosphate buffer solution) was contained. The cyclic reciprocating motion of the upper glass plate of 3.0 mm stroke length was produced using a slider-crank shaft mechanism that was linked to an eccentric cam-motor system. Each rotation of the motor produced a 3.0 mm stroke each in the forward and backward direction of the slider block. The clearance between the two glass plates was adjusted to 30 micrometer. The cyclic reciprocating glass plate apparatus was attached to a light microscope stage (IX71 Olympus with x40 objective lens) for illumination with a 350 watt metal halide light source. A high speed camera (MEMREMCAM fx-K3 Nac, 5000 frames per second with shutter kept open) was attached to the microscope to capture the deformation process of the RBCs under cyclic shear stress. The preliminary result indicated that the correlation between the amplitude of the maximum shear stress and the RBCs' deformability. This indicates a potential application of the cyclic reciprocating device to evaluate the temporal response of the RBCs deformability prior to its destruction. The future study will focus on the study of the relative velocity of the erythrocytes with respect to the velocity of the reciprocating plate. PMID- 17271458 TI - Preliminary look at why some vessels get atherosclerosis and others don't. AB - Atherosclerosis is a disease mainly of large, high pressure arteries and of valves, typically sparing veins and small, low pressure arteries. We investigate the resistances of the vena cava and the pulmonary artery to the flow of water and the infiltration of solutes into the vessel walls and compare them with similar processes in the aorta. The goal is to see if differences in macromolecular transport from the blood into the vessel wall amongst vessels can explain their different susceptibilities to atherosclerosis. PMID- 17271459 TI - Stress analysis of unilateral cleft palate using a three dimensional finite element model of pediatric subject-specific maxilla. AB - For children with cleft palate, oral function is impaired. The hypothesis is that the stress and strain distribution within the affected maxilla with a cleft during functional tasks such as biting and chewing is abnormal and can significantly affect bone development in the growing child. To test this hypothesis, a three-dimensional finite element model of a pediatric subject specific maxilla with and without unilateral cleft palate was established based upon pediatric subject-specific bony geometry. The stress and strain distribution of the maxillary alveolar region subjected to typical functional loads was analyzed. The preliminary results revealed that both Von Mises stress and maximum principle stress as well as principle strain distribution were unevenly distributed between the hemi-maxillae. PMID- 17271460 TI - Development of a three-dimensional finite element model of breast mechanics. AB - A typical breast cancer examination involves the comparison of image patterns in mammograms of craniocaudal (CC) and mediolateral oblique (MLO) views. Obtaining these mammograms requires the compression of the breast in two different directions. During compression, breast tissues undergo large deformations and hence the CC and MLO views do not show exactly the same region of the breast. Nonrigid body registration algorithms typically do not account for the mechanics of the deformation and are thus prone to alignment errors. Finite element model predictions of breast tissue deformation ensure that only physically plausible deformations are used in registration algorithms. A modeling framework has been developed to create anatomically accurate finite element models of the breast. A semi-automatic procedure has been formulated to generate patient specific finite element geometries of breast anatomy. Validation of model predictions has also been conducted on silicon gel samples subjected to gravity loading. PMID- 17271461 TI - The effect of hormone treatment on the plastic characteristic of osteoporotic vertebral trabecular bone. AB - Many researchers have investigated the elastic characteristic of trabecular bones by using the microfinite element (Micro-FE) models based on the microcomputed tomography (micro-CT). However, there were few micro-FE models to account for the plastic characteristic of trabecular bones. The present study analyzed the plastic characteristic as well as the elastic characteristic of the trabecular bone and evaluated the effect of specimen size on the plastic characteristic of vertebral trabecular bones. Previous researchers reported that a cubic specimen with side length 6.5 mm was suggested as a standard specimen for the experimental tests of trabecular bones. The present study examined whether the effects of the specimen size on the experimental tests may be also applied to the simulated compression test of trabecular bone specimens and investigated the effect of voxel resolution on the plastic characteristic of micro-FE models. The results illustrate that in the simulated compression test to analyze mechanical characteristics of vertebral trabecular bones, it is recommended to use a cubic specimen with side length 6.5 mm rather than a cubic specimen with side length 4 mm. It is also found that the hormone therapy is likely to be less effective than the amount reported by previous researcher for 2D models. PMID- 17271462 TI - FEM model for evaluating buttock tissue response under sitting load. AB - Development of a model for evaluating tissue compression during sitting has been hampered by limitation of implementing the anatomical and mechanical parameters of the various layers of tissue. This study proposes a new method to setup and validate a finite element model for buttock tissue to evaluate the tissue response under external sitting load. Multi-layer tissue deformation was measured with ultrasound imaging under simulated sitting load, applied and monitored through an indenter which integrates ultrasound probe and force/pressure sensors. Subject-specific FE model can then be setup and validated. Pilot test of this model revealed that the highest peak stress was found in the vicinity of the ischial tuberosity and the greatest deformation seen in the muscle layer. The authors conclude that this new method allows accurate multi-layer tissue deformation be obtained under close to real sitting load, therefore, provides a better way to evaluate tissue response to external sitting load for seated individuals in a true and subject-specific fashion, which may provide helpful information to improve the sitting comfort and prevent pressure ulcers in wheelchair bound individuals. PMID- 17271463 TI - Loading conditions and bone formation in the GH region of the shoulder. AB - The present study investigates how loading of the shoulder effect the formation of the trabeculae in the subarticular region of the gleno-humeral joint. Bone morphology was determined from scapular cadaveric specimens and finite element (FE) analysis was employed to analyse principal stress trajectories. Boundary conditions corresponded to five functional activities were considered. The results show deviations of the computed trajectories from actual trabecular lines obtained from the bone specimens ranged on average from 10% to 17%. Each activity produced different regional deviation corresponding to the specific loading condition. This study concludes that certain loading conditions are more significant in explaining the formation of the trabecular architecture. The results also suggest that due to the extra sensitivity of the front and the rear aspects of the "lateral region" to the loading conditions, these regions may be more indicative in reflecting shoulder injuries. PMID- 17271464 TI - Investigating stress-strain properties of in-vivo human skin using multiaxial loading experiments and finite element modeling. AB - A multiaxial testing rig has been designed to investigate mechanical properties of soft tissue membranes. This approach has the advantage over biaxial loading in that it can be used to investigate soft tissue membranes with complex structural architecture. A finite element model of tissue mechanics has been used to analyze the experimental data in order to evaluate the stress-strain relationship, and a forward solve algorithm developed to estimate material parameters values for a given constitutive law. The multiaxial testing rig and the finite element analysis have been used to evaluate the constitutive properties of in-vivo human skin. PMID- 17271466 TI - Motion analysis based on a multi-segment foot model in normal walking. AB - The foot, an exceedingly complicated system, is essential to move the body forward and to keep dynamic stability during gait. In most previous studies on gait analysis, the foot has been defined as a single rigid segment, which results in many problems to understand the foot motion in detail. The purpose of this study is to develop a multi-segment foot model that can help analyze biomechanics of the foot during gait. A 9-segment foot model with 8 major joints was developed in this study. In addition, it was applied to the 3D motion analysis to determine the kinematics and the kinetics of the foot in the normal walking. Understanding the detailed foot motions by the present multi-segment foot model would be very useful to diagnose patients with various foot diseases. PMID- 17271465 TI - Kinematic analysis of upper extremity joint motion in children using posterior walkers. AB - This study applies an upper extremity model to analyze motion in 25 children with cerebral palsy using posterior walkers. The study indicates that throughout a gait cycle, the shoulders and wrist are in extension and the elbows are flexed. It also reveals that the elbows are the most asymmetrical joint of the upper extremities during walker-assisted ambulation. PMID- 17271467 TI - Biomechanics of the double rocker sole shoe: gait kinematics and kinetics. AB - This paper reports the kinematic and kinetic changes in gait with bilateral double rocker sole shoe modifications. Three-dimensional motion analysis techniques were used to evaluate gait characteristics (temporal-spatial, kinematic, and kinetic measures) of forty (40) subjects while wearing baseline and double rocker sole shoes. Walking speed was unchanged by the double rocker modification. Sagittal plane motions showed significant change at the pelvis, hip, knee, and ankle. (p = 0.01). The toe-only rocker consistently resulted in increase in posterior pelvic tilt (p =0.01). Kinetic changes were observed at the hip in the sagittal and transverse planes, and at the knee and ankle in the sagittal planes. Changes in pelvic tilt and hip rotation were hypothesized to result from feelings of imbalance during ambulation with the double rocker sole shoe. PMID- 17271468 TI - Reducing whole-body vibration of vehicle drivers with a new sitting concept. AB - A new car seat design, which allows the back part of the seat (BPS) to lower down while a protruded cushion supports the lumbar spine, was quantitatively tested to determine its effectiveness in reducing whole-body vibration (WBV) in automobile drivers. Results on 12 drivers show that, by reducing contact between the seat and the ischial tuberosities (TTs), the new seating design reduced both contact pressure and amplitude of harmful vibrations transmitted through the body. Significant reduction of WBV, in terms of RMS and VDV, was found as large as 30% by this seating design (P < 0.05), especially at lumbar spine region. This reduction in WBV allows more sustained driving than permitted by conventional seating devices, by around 2 hours daily, before reaching harmful WBV levels. The new seating design also promotes improved posture by restoring normal spinal curvature. Such seating devices, implemented in cars, buses, large trucks, and other high-vibration vehicles, may effectively reduce the risk of musculoskeletal disorders among long term drivers. PMID- 17271469 TI - Solid modeling of human vocal tract using magnetic resonance imaging and acoustic pharyngometer. AB - This investigation uses a multi disciplinary approach to standardize a non invasive method for measuring human vocal tract morphology. A series of magnetic resonance imaging (MRI) scans are performed on the subject's vocal tract and a detailed three-dimensional model is created through image processing and computer modeling. The area and volume obtained from the solid model is compared with that obtained from the Eccovision acoustic pharyngometer. This establishes the accuracy of the solid model. The model is then used to develop other specific models through parametric modeling. This method is useful in creating solid models with limited geometrical information and helps researchers study the human vocal tract changes due to aging and degenerative diseases. PMID- 17271470 TI - Medical device excellence award winners. AB - Each year, a select number of medical devices are critically reviewed by a panel of experts composed of from clinical engineers, researchers, industry designers. The winners this year ranged from neonatal screening for hearing dysfunction to automated cervical cancer detection. All are innovative medical devices that represent the best of biomedical engineering ideas brought to practice and are being used to help improve the health of the general public. This session features some of this year's prestigious gold and silver medal winners. Come hear about their devices and the stories behind them. PMID- 17271471 TI - Vision correction with excimer lasers. AB - Excimer lasers were invented in 1975, and the first human eye treatment with VISX laser technology was in 1987. Since then many advances in LASIK surgery and related diagnostic and control techniques have led to improved vision correction with over 95% of patients corrected to 20/20 vision or better. This paper describes the development of excimer laser surgery and recent results, wavefront guided vision correction methods, and the equipment required to achieve these results. Specific requirements imposed on the 193 nm excimer laser, on the laser beam control, the electronic controls, and the controlling software have led to development of laser systems and diagnostic systems unique to LASIK surgery. These include development of a highly reliable laser system with tightly controlled energy output and precision beam shaping and positioning. This development and widely successful use in refractive surgery are reviewed in this paper. PMID- 17271472 TI - Bactericidal light. AB - Three methods of using intense light to destroy pathogens will be reviewed. 1. Ultraviolet destruction of viruses, bacteria, and the like. 2. Photodynamic therapy of photosensitized bacteria using exogenous photosensitizers. 3. Bacterial destruction in the near infrared of pigmented pathogens through selective photothermolysis: example of treatment for periodontitis. All three methods rely on the sensitivity to destruction by light of the pathogen being significantly lower than the sensitivity of the surrounding host tissues (favorable therapeutic ratio). Optical properties of host and pathogens will be discussed. PMID- 17271473 TI - Ophthalmic glucose monitoring using disposable contact lenses. AB - We have developed a range of disposable and colorless tear glucose sensing contact lenses, using off-the-shelf lenses embedded with new water soluble, highly fluorescent and glucose sensitive boronic acid containing fluorophores. The new lenses are readily able to track tear glucose levels and therefore blood glucose levels, which are ideally suited for potential use by diabetics. The fluorescence responses from the lenses can be monitored using simple excitation and emission detection devices. The novelty of our approach is two fold. Firstly, the notion of sensing extremely low glucose concentrations in tears, which track blood levels, by our contact lens approach, and secondly, the unique compatibility of our new glucose signaling probes with the internal mildly acidic contact lens environment. The new lenses are therefore ideal for the noninvasive and continuous monitoring of tear glucose, with a 15 minute response time, and a measured shelf life in excess of 3 months. In this invited article, we show that fluorescence based signaling using plastic disposable lenses, which have already been industrially optimized with regard to vision correction and oxygen / analyte permeability etc, may a notable alternative to invasive and random finger pricking, the most widely used glucose monitoring technology by diabetics. PMID- 17271474 TI - Center for Biophotonics Science and Technology (CBST). AB - The Center for Biophotonics Science and Technology (CBST) is the only center in the country funded by the National Science Foundation and devoted to the study of light and radiant energy in biology and medicine. Our consortium of 10 world class academic institutions and research laboratories is comprised of physical and life scientists, physicians and engineers - along with industry participants, educators and community leaders - working together to bring biophotonics to the forefront of mainstream science. The three main arms of CBST are (1) Science and Technology, (2) Education, and (3) Knowledge Transfer. The research sponsored by the center focuses on critical themes that are expected to have significant impact on current biomedical science and technology. Projects include the development of new methods in optical microscopy that work well beyond the diffraction limit; ultrafast, high-intensity X-ray lasers to resolve the structure of single biomolecules, and new devices and sensors for minimally - or noninvasive medical applications. CBST is developing a new curriculum, along with training materials, internships and research fellowships to introduce biophotonics to students and teachers at all educational levels. Finally, the knowledge transfer component of CBST is seeking to catalyze the rapid growth of biophotonics as a new technology sector by supplying intellectual capital and tools to stimulate the growth of new products and new companies. By coupling the center's biophotonics research projects with industry partners and sponsors, a unique R&D environment is created to expand the use of photons in the development of life sciences, bioengineering and health care. PMID- 17271475 TI - New methods for automated phenotyping of complex cellular behaviors. AB - Cellular shape change and movement are central to biologic processes that range from normal embryonic development to inflammatory diseases and cancer. Quantitative visual phenotyping of dynamic cellular behaviors creates unique challenges for image capture, analysis and storage. Despite substantial technological advances in molecular biology, biochemistry, genomics and proteomics, investigating cellular processes remains tremendously challenging and labor-intensive. We have developed algorithms and software implementations that allow for fully-automated analysis of experiments designed to investigate a range of cellular and organismal behaviors. By enabling cellular phenotyping, this automated approach creates a unique opportunity for investigators to perform large-scale experiments designed to determine gene function or to screen for small molecule modulators of important cellular behaviors. PMID- 17271476 TI - Commercialization of computer assisted detection: the path from science to product. AB - Computer Assisted Detection (CAD) is a rapidly growing field with applications in a growing number of diseases, modalities, and anatomies. Academic and industrial research groups worldwide are proposing and publishing new approaches, techniques, and paradigms at an ever-increasing rate: The results are encouraging and imply the potential for dramatic improvements in disease detection and tracking. To researchers, it often seems curious that commercialization of these advances lags far behind academic progress, but there are many obstacles to be overcome, from IP management to QSR (Quality Systems Regulations) compliance, from image data and truth collection to GCP (Good Clinical Practices), from bio statistics to proof of Safety & Effectiveness with regulatory agencies. This two hour session is designed to shed light on experiences in CAD commercialization of innovative CAD technologies into the marketplace. The goal is to share best practices, non-competitive ideas, and "mistakes not to be repeated" among the seminar participants and with researchers in industry and academia. All speakers are involved in bringing a variety of CAD applications to market. Panelists are: Susan Wood--R2 Peter Whitehead--Quantitative Imaging Michael Yeh--Deus Chris Wood -Confirma Fred Lachmann--Medipattern Alok Gupta--Siemens Patrick Hess--Imatx Wido Menhardt--Eastman Kodak. PMID- 17271477 TI - RF ablation of intestinal metaplasia (Barrett esophagus). AB - Esophageal intestinal metaplasia, otherwise known as Barrett's Esophagus, is a pre-cancerous condition that afflicts over 1 million Americans annually. Barrett's Esophagus is caused by chronic esophageal exposure to stomach acid which can occur in patients afflicted with Gastro Esophageal Reflux Disease (GERD). The lining of the esophagus undergoes a metaplastic change, from normal squamous cell epithelium to columnar cell epithelium. Over time, this condition can progress to dysplasia and ultimately to adenocarcinoma. Currently, there are no widely practiced therapies for Barrett's Esophagus. Patients diagnosed with this disease are routinely screened to ensure do not have cancer, yet. It has been shown that if the GERD is controlled (i.e. a normal esophageal pH is maintained) and the metaplastic lining of the esophagus is carefully removed, i.e. no damage to underlying tissues), the normal squamous epithelial cells will repopulate the esophagus. A system has been designed to couple radiofrequency (RF) energy to the epithelial lining of the esophagus to effectively ablate the metaplastic cells and allow normal squamous cell repopulation. The design principles of this system and the resulting effects are the subject of this presentation. PMID- 17271478 TI - BioMEMs. AB - This session is intended to provide insight into the development of BioMEMS in the academic and industrial settings and address the current challenges facing R&D. Each speaker will address the field of bioMEMS and collaborations between academia and industry from his point-of-view and provide examples of developmental successes and failures in his setting. The speakers will also submit potential solutions to the organizational problems they presently face and foresee in the future. As a panel, the speakers will exchange ideas with the attendees with the hope of collectively introducing solutions to the problems submitted during the talks and general guidelines for successful R&D of BioMEMS through productive collaboration among engineers and scientists of different disciplines and between academia and industry. Speakers: Professor Kensall D. Wise (Professor of EECS and Director of WIMS, U of Michigan), Dr. Michael A. Huff (Director of the MEMS Exchange), Colin Brenan (CTO, Biotrove). PMID- 17271480 TI - From concept to exit strategies--medical device innovation. AB - It's quite a rollercoaster ride when you are part of a medical device start-up team. There are often many partners and processes that are not often taught in school or in the training to do research . For example, how does one obtain financing, protect intellectual property, set up a business, work with contract designers and/or manufacturers? Bringing a medical device business into existence is challenging and generally, only one in 10 medical device start ups make it. This lively 2-hour session brings together panelists with many years of start-up experience to give the audience a perspective of the many facets and ways to successfully (and sometimes not so successfully) bring a product to market. This is a panel discussion on the "nuts and bolts" of medical device innovation, how to do it, what to watch out for, a sharing of experience and lessons learned. The panelists include: Amir Belson M. D.--Neoguide Systems Thomas Conn--consultant Tom Goff, Kerberos MD; Eric Goldfarb--Evalve Sorin Grunwald, Ph.D./MBA--BC Tech Nicole Walker--Onset Ventures D.J. Williams, PhD--Loughborough University. PMID- 17271481 TI - Business models and leadership styles in small medical device and bio-science businesses--examples in a region and their implications. AB - This paper reviews the leadership styles and business models found in small technologically based businesses operating in the healthcare sector within one of the UK regions, the East Midlands. The most frequently encountered business model strands were 1) mixed economies: that fund development with service income; cross sectoral product portfolios; and decoupled business portfolios led by a single entrepreneur and 2) scale sensitive "stay small" models including the avoidance of venture capital; "early exit"; and virtual business strands. There was found to be little correlation between leadership style and business model for the small number of businesses surveyed. The avoidance of venture capital is in direct contrast to adjacent regions. PMID- 17271482 TI - Design and execution of clinical studies for medical devices. AB - You have a great new medical device that had good results in your animal studies and now you want to test it in a clinical study on human subjects. What are the key steps in designing and executing human subject studies so you can use the data to support your regulatory submissions? Some aspects that will be covered in this discussion group are the steps generally required to set up and manage a study of a medical device that complies with the Good Clinical Practices (GCP). This discussion will focus primarily on the requirements for clinical studies that will be used to support evidence of safety and effectiveness to the FDA. PMID- 17271483 TI - Getting your medical device cleared for marketing in the U.S. AB - This discussion group will explore the different requirements for getting a medical device cleared for marketing in the United States. Specifically, the discussion leaders will give an overview of the 510(k) and PMA, registration, and listing processes. The discussion will also include what is required for foreign companies who wish to import medical devices. The discussion group leaders include Robert Munzner, a former branch chief for the Office of Device Evaluation at the FDA, and Grace Bartoo, a regulatory consultant with over 20 years in the imedical device industry. The format of this session is a discussion group, so please bring your questions and experiences to share. PMID- 17271484 TI - Meetings with the FDA. AB - For new and innovative medical devices, a company is most likely to have direct communications with the FDA at some course during the product lifecycle. Most often these are meetings relating to what type of information is required in the marketing application (510(k) or PMA) and discussions relating to approval of the device. This session will explore the different types of meetings, preparation methods, and what to expect when you are at FDA. The discussion group leaders include a former FDA ODE Branch Chief who will provide his perspective. The format of this session is a discussion group, so please bring your questions and experiences to share. PMID- 17271485 TI - Industry careers for the biomedical engineer. AB - This year's conference theme is "linkages for innovation in biomedicine." Biomedical engineers, especially those transitioning their career from academic study into medical device industry, will play a critical role in converting the fruits of scientific research into the reality of modern medical devices. This special session is organized to help biomedical engineers to achieve their career goals more effectively. Participants will have opportunities to hear from and interact with leading industrial experts on many issues. These may include but not limited to 1) career paths for biomedical engineers (industrial, academic, or federal; technical vs. managerial track; small start-up or large established companies); 2) unique design challenges and regulatory requirements in medical device development; 3) aspects of a successful biomedical engineering job candidate (such as resume, interview, follow-up). Suggestions for other topics are welcome and should be directed to xkong@ieee.org The distinguished panelists include: Xuan Kong, Ph.D., VP of Research, NEUROMetrix Inc, Waltham, MA Robert F. Munzner, Ph.D., Medical Device Consultant, Doctor Device, Herndon, VA Glen McLaughlin, Ph.D., VP of Engineering and CTO, Zonare Medical System Inc., Mountain View, CA Grace Bartoo, Ph.D., RAC, General Manager, Decus Biomedical LLC San Carlos, CA. PMID- 17271486 TI - Technology transfer. AB - A wealth of innovation comes from the academic community. In order to make this innovation useful to the public, the technology is typically transferred to the industry sector where the ideas are developed into a product that can be robust, safe and effective. The workshop leaders have great experience in transferring technology from their academic labs and managing intellectual property. Come hear about their experiences and recommendations. The format of this session is a discussion group, so please bring your questions and experiences to share. PMID- 17271487 TI - FDA rules for R&D also: root cause analysis and failure investigations. AB - This session discusses successful methodologies and regulatory documentation required for Research and Development scientists and engineers during development, animal and clinical testing and marketing of medical devices and drug device combinations. The session will be a guided roundtable in which the development lifecycle will be discussed in terms of common regulatory pitfalls. Group experiences will be shared during the session. Topics discussed will include: documentation required for various regulatory pathways, lab organization under GMPs for R&D vs. GMPs for QC, and FDA audit experiences in the R&D lab. PMID- 17271488 TI - Development of educational tools to demonstrate the effects of hyper and microgravity on different test bodies. AB - Educational and outreach programs in space sciences have been a major concern since the beginning of the Space Era. Education curricula in Brazil rarely consider topics related to manned and unmanned space flight. This lack in the Brazilian education system has motivated the development of educational tools, used to demonstrate the effects of hyper- and microgravity on test bodies, both gravitational environments commonly found in aerospace missions. This paper presents the conception and development of a lift and a centrifuge for microgravity and hypergravity research use, respectively. Experiments were recorded via a digital camera and the images acquired were processed for better visualization of the effects of simulated variation in the gravitational force on test bodies. A CD-ROM was then produced for academic purposes. The final goal of this study is to motivate the insertion of space science related topics in the Brazilian elementary and high schools curricula. PMID- 17271489 TI - Graphic-user-interface system for people with severely impaired vision in mathematics class. AB - Computer software is more and more developed based on graphic-user-interface system (GUI) in order to be user-friendly program. However, this development creates some difficulties for people with impaired vision to use the computers. The "Braille Box", an assistive device, has been developed by modifying Braille cells to form a tactile stimulator array which is compatible with the fingertip. This device allows people with impaired vision to access graphic information on computer screen by tactile perception. We applied the "Braille Box" in mathematics class focused on linear graph, with visually impaired children. The result shows that they can perform task as determining the slope, the intercept and the coordinates of the intersection of two lines. PMID- 17271490 TI - Experience with the first three years of an accelerated dual-degree program in biomedical engineering. AB - Our Department of Bioengineering has instituted a pilot program aimed at helping a select group of highly qualified students obtain both bachelor's and master's degrees in an accelerated timeframe - approximately four years from the beginning of their university studies. A key element of this program is the introduction of the students to research in their second year of studies via a directed and closely supervised cohort mechanism. These students also come to the university with substantial AP credit and spend two summers fulfilling some general education requirements of the university. Our first three years with the program have shown positive results, with most students on track in both academics and research. There have been some challenges, however, with regard to tight scheduling, leaves for religious missions, and continued student stipend funding. PMID- 17271491 TI - An overview of the integrated laboratory course of physiological sciences at Zhejiang University in China. AB - An integrated laboratory course of physiological sciences has been put into use at Zhejiang University School of Medicine since 1993. This course guides students in taking a scientific approach to understanding the contemporary issues in physiology, pathophysioiogy and pharmacology. Students learn to use a variety of basic experimental methods to laboratory work. More importantly, research oriented experiments are integrated in this course, offering students an opportunity to hone their skills in critical thinking and problem solving. Research presentation skills, both written and oral, are also emphasized. This integrated laboratory course is highly appreciated by students and medical educators. We recommend this innovative teaching format as a more integrated approach to medical education. PMID- 17271492 TI - Empowering biomedical engineering undergraduates to help teach design. AB - We report on our experience empowering upperclassmen and seniors to help teach design courses in biomedical engineering. Initiated in the fall of 1998, these courses are a projects-based set, where teams of students from freshmen level to senior level converge to solve practical problems in biomedical engineering. One goal in these courses is to teach the design process by providing experiences that mimic it. Student teams solve practical projects solicited from faculty, industry and the local community. To hone skills and have a metric for grading, written documentation, posters and oral presentations are required over the two semester sequence. By requiring a mock design and build exercise in the fall, students appreciate the manufacturing process, the difficulties unforeseen in the design stage and the importance of testing. A Web-based, searchable design repository captures reporting information from each project since its inception. This serves as a resource for future projects, in addition to traditional ones such as library, outside experts and lab facilities. Based on results to date, we conclude that characteristics about our design program help students experience design and learn aspects about teamwork and mentoring useful in their profession or graduate education. PMID- 17271493 TI - The universe of activity that is bioengineering research. AB - What is bioengineering? A concise and meaningful answer to this question is important for pedagogy. This paper demonstrates that research activity within 'bioengineering' resides in a multidimensional space. A specific study can be characterized by an area into which it falls, a problem that it attacks, a specific level of analysis, a species of focus, pertinent disciplines, relevant tools that are employed, and temporal features. Each represents a dimension of the universe and each dimension may be shown to be largely orthogonal to every other dimension. The universe thus defined is sparsely populated. Accordingly, bioengineering is a field of rich opportunity within which frontiers lie almost everywhere. PMID- 17271494 TI - IRiS: an interactive reality system for breast self-examination training. AB - This paper presents a novel interactive reality video playback approach developed for biomedical training purposes, and tested on a prototype breast self examination (BSE) multimedia training application. The system is developed in order to improve on existing video playback approaches as used in multimedia applications by providing control over not only time, as in conventional video playback, but also space. The benefits of interactive reality video playback are presented and the approach is compared with other similar approaches, such as QuickTime and iPIX. The design, development, final implementation, testing and evaluation plan of the IRiS system are presented. The paper also discusses future plans and the use of the system in other biomedical training scenarios. PMID- 17271495 TI - Building interactive simulations in a Web page design program. AB - A new Web software architecture, NumberLinX (NLX), has been integrated into a commercial Web design program to produce a drag-and-drop environment for building interactive simulations. NLX is a library of reusable objects written in Java, including input, output, calculation, and control objects. The NLX objects were added to the palette of available objects in the Web design program to be selected and dropped on a page. Inserting an object in a Web page is accomplished by adding a template block of HTML code to the page file. HTML parameters in the block must be set to user-supplied values, so the HTML code is generated dynamically, based on user entries in a popup form. Implementing the object inspector for each object permits the user to edit object attributes in a form window. Except for model definition, the combination of the NLX architecture and the Web design program permits construction of interactive simulation pages without writing or inspecting code. PMID- 17271496 TI - An interactive electrophysiology training resource for simulation-based teaching and learning. AB - An interactive electrophysiology training resource was developed for computational modeling of cellular bioelectric activity. Electrophysiology research projects were integrated into education and training by this resource called iCell which is also known as the interactive cell modeling tool (http://ssd1.bme.memphis.edu/icell). iCell is used as a simulation-based teaching and learning tool for electrophysiology. The site consists of JAVA models of various cardiac cells and neurons, and provides simulation data of their bioelectric activities at single cell level. Each JAVA-based model is menu-driven and presents options to change model parameters or conditions, run and view simulation results. iCell has been used as a teaching and learning tool for seven graduate courses at the Joint Biomedical Engineering Program of University of Memphis and University of Tennessee. Scientists from the fields of biosciences, engineering, life sciences and medicine in 17 different countries have also tested and utilized iCell as a simulation-based teaching, learning and collaboration environment. PMID- 17271497 TI - Medical imaging curriculum development: an interactive simulation system for different modalities. AB - This paper presents the result of our recent development for medical imaging education, an Internet-based interactive medical imaging simulation system. A series of popularly used medical imaging modalities, including X-rays, ultrasound, CT, MRI and PET, are explored through text, relevant graphics and simulations. In this development, we emphasize interactivity by using MATLAB and Shockwave simulations. To develop the online interactive medical imaging tutorial, MATLAB Web Server and Internet technologies such as Director MX, JavaScript and HTML are employed. PMID- 17271498 TI - Porting GENESIS to SIMULINK. AB - This paper describes the porting of the general simulation system (GENESIS) to Matrix Language Laboratory language (MatLab) SIMULINK, based in the cable theory to simulate the behavior of neurons. A graphic programming approach serves as ideal platform for teaching physiological modeling and neuroengineering courses. The ultimate goal of this project is to integrate all of the chemical, electrical, material, mechanical and neural interactions into a single model that can be viewed seamlessly from a molecular model to the large scale model. Integration of all interactions is not possible with GENESIS, but can be accomplished with SIMULINK. PMID- 17271499 TI - Bridging biomedical basics with practical applications in BME laboratory education. AB - A sophisticated biomedical engineering (BME) laboratory course was designed to integrate state-of-the-art technology with a hands on learning approach in a flexible, virtual-based, clinical application setting. The need for biomedical engineers in research and industry has increased rapidly in recent years. This requires that innovative methods for training BME students evolve to meet that need. BME students should be prepared with a skill set for approaching practical problems. BME education requires hands on learning with cutting edge technology to produce students ready to solve clinical problems in research and industry. Exposing students to a wide range of BME applications not only increases interest, but also better prepares them to solve real world problems. A wide range of BME laboratories have been designed to encompass both the basics of physiological signals and how to effectively utilize them in practical applications. These application interfaces are critical for students to understand how physiological signals may be manipulated to produce meaningful benefits for various medical disorders and rehabilitation needs. The laboratory course presented in this paper was implemented and evaluated at several universities. Utilizing the virtual environment for practical applications bridges the gap between fundamentals and real world designs. PMID- 17271500 TI - Upgrading the biomedical engineering undergraduate curriculum based on current trends in higher education. AB - This paper presents the reforming of the curriculum of the Department of Medical Instrumentation Technology at the Technological Educational Institution of Athens (TEI-A), as inspired by current trends in higher education. The reforming is taking place in the framework of the "Upgrading of Undergraduate Curricula of TEI A" project The project-funded upgrading focuses on a core of eight laboratory sectors, with particular emphasis placed on student-centered learning, taking advantage of computer-enhanced educational environment. The existing and proposed curricula are compared. The student workload in the proposed curriculum is reduced, while maintaining an extensive set of basic and applied knowledge related to biomedical engineering. The overall aim is to provide a curriculum that will help in developing multi-skilled individuals that can relate to the demands of this field within a dynamic social and economical environment. PMID- 17271501 TI - The importance of multidisciplinary teams in a large biomedical research program. AB - The formation of multidisciplinary teams is vital to modern biomedical research. These teams are important contributors to the advancement of scientific discovery as well as the translation of those discoveries into useful clinical practice. The issues involved in providing scientific and technical expertise in computational science and engineering to support a large biomedical research program are presented. The activities of the Division of Computational Bioscience (DCB) of the Center for Information Technology (CIT) at the National Institutes of Health (NIH) are highlighted. Professionals in this organization apply the concepts and technologies of computer science, engineering, physical science and mathematics to biomedical applications, making available this expertise to the NIH Intramural Research Program (IRP). The areas of application include imaging, informatics, instrumentation, telemedicine, structural biology and mathematical analysis. Examples where collaborative research and development teams containing DCB professionals have worked to produce significant results are presented. These examples are a chromosome microdissection instrument, a telemedicine system for radiation oncology, and a medical image archive. PMID- 17271502 TI - Maxi program at IEEE EMBS Student Club of Beijing University of Posts and Telecommunications. AB - This paper presents the recently launched Maxi Program at IEEE EMBS Student Club of Beijing University of Posts and Telecommunications. The program initiates a variety of seminar series covering biomedical expertise and professional communication skills, forms a cooperative partnership between students, university and industry through guest speakers events and industry tours, and sets in motion personal consultative services (PCS) to foster the individualized competence of students. This extended program could be an innovative model of self-development as an affiliated student chapter/club with IEEE EMBS. PMID- 17271503 TI - Biomedical engineering chapters and student societies: a UK and Republic of Ireland perspective. AB - Biomedical engineering is a thriving academic and industrial subject in the United Kingdom and Republic of Ireland (UKRI). We describe how the EMBS UKRI Chapter and EMB Student Society UKRI are trying to support this field. Geographical constraints and the smaller number of biomedical engineering undergraduate students mean that the Chapter and Student Society have been formed at a national level, rather than the conventional University-based clubs and societies typical in North America. The style of events is also slightly different, with a focus on conferences rather than short events lasting less than one day, offering increased value for delegates who have to travel significant distances to attend. The UKRI Chapter and Student Society are cooperating with related organizations in the UKRI, as well as drawing on various resources, to build on what has been achieved to date. PMID- 17271505 TI - A code of bioethics for promoting biomedical engineering. AB - The biomedical engineering profession is conceptually dynamic and its scope widens frequently to incorporate new disciplines and specialties. Engineers currently engage in a wider range of activities and BME stands as a clear example of strong multidisciplinary integration. We present a Code of Ethics which summarizes the broad scope of professional issues and responsibilities for biomedical engineers. Discussing the statements of such bioethical code has been instrumental in promoting the BME profession among high school and undergraduate students. PMID- 17271504 TI - Determination of the core undergraduate BME curriculum--the 1st step in a Delphi study. AB - The VaNTH Engineering Research Center for Bioengineering Education Technologies has completed the first round of a Delphi study to determine the key concepts that comprise the core curriculum of undergraduate programs in biomedical engineering. The study was conducted as a Web-based survey, consisting of eighty questions divided among nineteen topics, including eleven biomedical engineering domains, four biology domains, and mathematical and scientific prerequisites. Participants included representatives from academia, industry, and young alumni of undergraduate BME programs. Results from the survey will be available at: http://www.vanth.org/curriculum/. PMID- 17271506 TI - New continuing education programs for hospital and clinical engineering. AB - This paper describes the new continuing education efforts that are being made to offer degrees more in tune with the career path for clinical engineering or for engineers working at different hospitals. Following an analysis of the issues regarding the field of hospital engineering in Mexico, and the type pf professionals that provide this service, we have implemented a series of programs in order to provide a full spectrum of educational opportunities in biomedical engineering. Since the conventional research-oriented graduate program is doing well, and the number of faculty that is interested in clinical engineering is growing, we now offer professional development track for engineers working inside the hospital environment. PMID- 17271507 TI - Directions in biomedical research: the NIH Roadmap. AB - To develop a plan for making the National Institutes of Health (NIH) optimally effective in meeting its mission of improving human health and quality of life, a "NIH roadmap" was developed and is being implemented. The roadmap is a ten-year plan that is aimed at accelerating the pace of discoveries in the life sciences, rapidly translating discoveries into practice, and building an integrated system that is far more effective than current approaches. The presentation will cover specific focus areas associated with these objectives, related funding opportunities, and implications for the future of biomedical research. PMID- 17271508 TI - Biomedical imaging research opportunities at the NIH. AB - Biomedical imaging is a key aspect of clinical diagnosis and treatment of disease and research concerning disease genesis, progression, and therapy. The NIH offers research funding opportunities for imaging at the cellular/molecular levels and at the whole-body (diagnostic) levels. This presentation will discuss imaging programs and directions at the NIH and specific funding opportunities that encompass devices, informatics, and applications. PMID- 17271509 TI - Research opportunities in biomaterials and tissue engineering. AB - Materials applications in biology and medicine encompass a broad range of spatial scales and clinical needs. At the cellular/molecular scale, tissue engineering offers significant opportunities for basic and applied research related to reparative and regenerative medicine. At the macro-scale, there is a wide variety of research needs for materials used in devices, implants, and prosthetics. The presentation will cover research programs and funding opportunities at the NIH for micro- and macro-scale materials research. PMID- 17271510 TI - Science and engineering research opportunities at the National Science Foundation. AB - Research at the interface of the physical sciences and life sciences has produced remarkable advances and understanding in biology and medicine over the past fifty years. These bases for many of these healthcare and research advances have been discoveries in the quantitative sciences and engineering approaches to applying them. The National Science Foundation supports research and development in the physical sciences which underpins multi-disciplinary approaches to addressing problems in biology and medicine. This presentation will cover research opportunities offered by the NSF and collaborative programs with the NIH to transfer the resulting advances and technologies. PMID- 17271511 TI - Novel engineering approaches to obesity, overweight, and energy balance: public health needs and research opportunities. AB - The obesity epidemic is one of the most rapidly evolving public health problems of our day. At present, 2/3 of American adults and 1/6 of American children and adolescents are considered either overweight or obese. Public health concern about obesity is high and reflects documented increased risk of cardiovascular disease, type 2 diabetes, many forms of cancer, gallbladder disease, and osteoarthritis, and increased mortality from these ailments, especially among the most obese. Innovative engineering technologies are needed to address a large range of problems in energy balance, intake, and expenditure that are associated with the obesity epidemic. Excess adipose tissue, representing fat storage, ultimately derives from an imbalance between energy intake and energy expenditure. Novel sensors, devices, imaging technologies, nanotechnology, biomaterials, and other approaches need to be developed and evaluated through multidisciplinary collaborations between engineers, physical scientists, and scientists with expertise in obesity and nutrition. The goal is to encourage research to develop useful technologies and tools to facilitate research and eventually to support therapeutic advances and behavioral change. Furthermore, the possibility of re-engineering the "built environment" to encourage higher levels of physical activity has been suggested as another promising and important approach to which engineers can contribute (see http://www.obesityresearch.nih.gov). PMID- 17271512 TI - Novel engineering approaches to obesity, overweight, and energy balance: public health needs and research opportunities. AB - A major national health concern is the rapidly increasing incidence of obesity among people of all ages. Overweight conditions are associated with a wide variety of health problems, and costs associated with dealing with this issue are expected to be very high. Obesity offers opportunities for novel engineering approaches to deal with the diagnosis and treatment of the basic condition and related disorders. This presentation will cover health care needs and research opportunities related to obesity and overweight conditions. PMID- 17271513 TI - Electronic house calls: high-tech medicine at your doorstep. AB - The traditional healthcare system is characterized by hospital or clinic-based face-to-face contacts between the patient and care provides, which frequently occur at times and locations that are inconvenient or difficult for the patient. The healthcare delivery in the future needs to be provided in a distributed, patient-centered manner. The distributed diagnosis and home healthcare (D2H2) will benefit patients, particularly those with chronic disease, e.g., diabetes, arthritis, and high blood pressure, by improving the quality, convenience and efficiency of care, reducing the healthcare cost, and preventing medical errors, thus leading to increasing access to affordable and effective healthcare. There are many important components to make the D2H2 vision a reality: (1) physiological measurement and point-of-care diagnostic devices that can be used at the place where the patient is, e.g., home and nursing home, (2) a home-based controller, (3) communications and networking, (4) databases, Web servers and services, (5) biomedical informatics, (6) intelligent agents, and (7) system integration, reliability and security. We believe that the paradigm change from central, hospital-based to distributed, patient-centered, home-based healthcare delivery is inevitable. There are many opportunities for engineers and scientists to innovate and contribute to this 21st century healthcare system. PMID- 17271514 TI - Bioelectromagnetism--relative merits of electric and magnetic measurements in cardiac studies. AB - This lecture gives a general overview to the relationship of bioelectric and biomagnetic phenomena: The most important issue in bioelectromagnetism is: Are the biomagnetic measurements independent on bioelectric ones and do they bring new information from the source or are they only a different modality of the same phenomenon? This issue is discussed with application on cardiac studies. The three orthogonal dipolar magnetic leads (vector magnetocardiography) are equal in the sense of diagnostic performance to the three dipolar electric leads (vector electrocardiography). Therefore the VMCG has quite the same diagnostic performance as the VECG. We have shown with a patient material of 313 subjects that when combining these methods to vector electromagnetocardiography, VEMCG, the number of incorrectly diagnosed patients may be decreased to one half. This is a statistically significant improvement in the diagnostic performance. We have also proven that our explanation for the Helmholtz's theorem is correct: What are fully independent are the lead fields of electric and magnetic measurements, not the signals. The dipolar electric and magnetic signals are similarly independent from each other as the three orthogonal dipolar electric signals are. PMID- 17271515 TI - Microfabricated sensors for biomedical applications. AB - Biomedical sensors couple physiological variables in living and other biologic systems to electronic instrumentation for making measurements. Microfabrication technology such as used in the microelectronics industry has been applied in the fabrication of biomedical sensors. Thin- and thick-film processing is especially well-suited to fabricating physical and chemical sensors due to the special properties of these films and the relative low costs for their production compared to other microfabrication technologies. These technologies can yield reproducible, batch-fabricated, and relatively inexpensive sensors. Devices such as biopotential electrodes, chemical sensors, temperature sensors, and transducers for measuring force and displacement can be fabricated using these techniques, and their small size and relatively low cost makes them especially useful for biomedical applications. Examples of devices produced over the years by our group at Case Western Reserve University, Duke University, the University of North Carolina and the Memphis Joint Program in Biomedical Engineering include: thin-film infant biopotential electrodes, thin- and thick-film temperature sensors, ion-selective electrodes, and microcell bioanalytical sensors. The multidisciplinary, multi-university program has made it possible to study biomedical sensors from fundamental underlying principles through biomedical applications. PMID- 17271516 TI - Contrast mechanisms and acquisition methods in functional MRI. AB - Functional brain imaging using MRI (functional MRI or fMRI) has become a valuable tool for studying function/structure relationships in the human brain in both normal and clinical populations. This paper describes the physiological changes associated with brain activity, including changes in blood flow, volume, and oxygenation. The latter of these, known as blood oxygenation level dependent (BOLD) contrast, is the most common approach for functional MRI, but it is related to brain activity via a variety of complex mechanisms. Here we describe a physiological and fluid mechanical model that can explain the shape and behavior seen in the BOLD response and may allow for improved quantification of the measured response. We also describe basic acquisition methods used in BOLD fMRI and associated artifacts. Finally, we briefly introduce approaches to acquired alternate contrast mechanisms in fMRI. PMID- 17271517 TI - Diffusion tensor imaging: techniques and clinical applications. AB - Diffusion tensor imaging (DTI) is a fast evolving MRI technique that can be used to visualize the white-matter fiber tracts in vivo. Recent technological developments have resulted in a broad range of DTI clinical applications. This presentation briefly reviews the essential principles of DTI, discusses some recent technical developments, and describes several selected clinical applications. PMID- 17271518 TI - Experimental design and analysis in functional MRI. AB - As the experimental diversity of functional magnetic resonance imaging (fMRI) has grown since introduction of the technique in 1991, the appropriate application of statistical evaluation has become a significant research need. Advances in our understanding of both the dynamics of the underlying neurophysiology and the measurement process make fMRI a fertile ground for novel signal and image processing research. Recent analysis procedures seek to incorporate knowledge of the temporal and spatial characteristics of the blood oxygenation level dependent (BOLD) response measured by fMRI. Efforts that incorporate the nonstationary aspects of the BOLD response will become more important as future applications of fMRI are likely to be in conjunction with additional imaging modalities (e.g., fMRI combined with EEG) to acquire more complete physiologic data and permit greater refinement of our characterization of the central nervous system responses arising due to an applied stimulus. PMID- 17271519 TI - Arterial spin labeling for quantitative functional MRI. AB - BOLD effect imaging is very effective for detection and localization of brain activity, and is the dominant functional imaging technique in cognitive psychology. Despite its efficiency to detect and localize active site, the technique does not lend itself easily to quantifiable measurements. A growingly popular alternative is the use of arterial spin labeling (ASL) to obtain perfusion maps as the indicator of cerebral activation. In this paper, the principles and challenges of arterial spin labeling are discussed and the development of a new fast, two-coil pseudo-continuous labeling scheme is presented. The new scheme permits collection of a multi-slice subtraction pair in less than three seconds, depending on the subject's arterial transit times. The theoretical basis of the technique, as well as a model for quantification of perfusion from the ASL data, are presented. Experimental data from functional imaging experiments were collected to demonstrate the technique and its characteristics. PMID- 17271520 TI - Functional brain imaging with BOSS FMRI. AB - The standard method for FMRI, using the blood oxygenation level dependent (BOLD) effect, has significant limitations that result from the coupling of functional contrast to sources of image artifact. We have developed an alternative method for FMRI based on balanced-SSFP imaging. This method uses the balanced-SSFP phase profile to invert the signal in deoxygenated blood relative to oxygenated blood. The resulting blood oxygenation sensitive steady-state (BOSS) signal decouples functional contrast from imaging, enabling significantly better image quality than BOLD FMRI. BOSS FMRI is very SNR-efficient, achieves strong functional contrast and is relatively immune to susceptibility gradients. In this paper, we present results validating the ability to detect functional activity using BOSS FMRI. One of the potential advantages of BOSS FMRI is the ability to acquire high resolution data due to the SNR efficiency of balanced-SSFP. Preliminary high resolution results (1 x 1 x 2 mm/sup 3/) at 1.5 T are presented. PMID- 17271521 TI - Non-invasive assessment of tumor proliferation using triple quantum filtered 23/Na MRI: technical challenges and solutions. AB - We address the development of triple-quantum-filtered sodium MRI as a non invasive surrogate measure for cell proliferation in brain tumors. We demonstrate that through careful consideration of the theoretical description of the signal, triple-quantum-filtered sodium images of adequate signal-to-noise ratio (SNR) can be acquired in clinically acceptable imaging times. PMID- 17271522 TI - A nanotechnology-based analog of monoclonal antibodies for targeted delivery of diagnostic and therapeutic agents. AB - The goal of our research is in vivo molecular and cellular imaging. This includes but is not limited to the imaging of protein expression. Dendrimers are an extremely monodisperse polymer used in many types of targeted delivery. Dendrimer families currently used have only one type of surface functional group. Thus when adding both targeting and reporter molecules one gets an ensemble of dendrimer based agents with different avidities. This is analogous to the production of polyclonal antibodies which are a solution of different proteins that bind to the same target with different affinities, and avidities. Using tris-ester protected acids and alpha,omega-protected triamine building blocks we created a dendrimer family with two or more different types of surface functional groups and different protecting groups. This framework technology allows the independent and quantitative addition of targeting, reporter, and/or therapeutic molecules. This provides a solution of identical molecules all with the same avidity and affinity for the target, much like monoclonal antibodies. PMID- 17271523 TI - Efficiency of transfection and localization of superparamagnetic iron oxide particles in neural progenitor cells using two methods. AB - Stem cells represent a potentially revolutionary therapy for neurological pathologies but for which a thorough investigation of cell behavior in the living nervous system has yet to be performed. Contrast-enhanced cell tracking with magnetic resonance imaging can enable this investigation by introducing superparagmagnetic iron oxide (SPIO) particles within the cell membrane. Before magnetically labeled cells can be observed in vivo, it is essential to maximize SPIO transfer into the cell and to fully understand the localization of the contrast agent in mature neural cells. For practical applications, a quantitative evaluation of labeled cells before implantation will allow in vivo assertions. In this study, we present a comparison between two methods for magnetic transfection of neural progenitor cells: the hemmaglutinating virus of Japan envelope (HVJ-E) as a viral vector and a liposomal reagent. We show that HVJ-E is a more efficient vehicle of cell transfection using quantitative evaluation and that the iron content per cell can be predicted using a simple, automated image analysis of stained, labeled cells. Image analysis is also used in this study to show that the contrast agent is distributed in the axon after differentiation, an important aspect of understanding cell tracking in vivo. PMID- 17271524 TI - Toward imaging the dynamic interaction between actin and myosin using a wet-cell C-mode near-field optical microscope. AB - This paper describes the implementation of a wet-cell collection-mode near-field optical microscope that has been constructed with the long term goal of imaging the myosin conformational change as it interacts with actin. The bioassay used to prepare the samples involved lysing muscle fibers to exact and myosin molecules which were fixed to a mica slide. Next, actin filaments were exacted and deposited in the region of the myosin. The wet-cell allows the addition of water containing ATP and the necessary ions to activate the myosin biomolecules. The near-field optical microscope was shown to able to resolve features of the size of the actin and myosin biomolecules. PMID- 17271525 TI - Engineering lanthanide complexes with controlled water exchange rates for magnetic resonance imaging. AB - The control of the rate of water exchange in lanthanide complexes is critical to their future development as contrast agents in magnetic resonance imaging. In traditional T/sub 1/ shortening agents an optimal water residence lifetime (tau/sub M/) of around 25 ns is required if the highest relaxivities are to be achieved. In contrast the newer PARACEST agents require that water exchange is much slower with tau/sub M/ on the order of microseconds. It is now possible to rationally design complexes that exhibit water exchange rates that are ideal for their intended use. The selection of appropriate ligating groups allow a broad control mechanism. Anionic ligating groups such as carboxylates favour faster exchange whereas neutral ligands such as amides favour slower exchange. By altering the steric hindrance around the water coordination site water exchange rates can be fine tuned. The steric hindrance can be altered by controlling the coordination environment of the lanthanide ion and optimal water exchanges rates so achieved. PMID- 17271526 TI - Clinical study on using thermal texture maps in SARS diagnosis. AB - This paper helps define infrared (IR) imaging as a complementary tool to high speed computer tomography (CT) in the diagnosis of severe acute respiratory syndrome (SARS). We refer to the images captured from IR imaging as thermal texture maps (TTM). Although IR imaging has been criticized of generating high false alarm rate for the lack of quantitative measurement on the size, depth, and shape information of the tumor, we present a new methodology that reveals the depth information and the activity of tumor from processing the surface temperature. The derivation is obtained without solving the ill-posed inverse heat transfer problem. We evaluate the clinical value of TTM in SARS diagnosis and compare the performance with CT. The study took place at Beijing You An Hospital, Beijing, P. R. China. It was conducted on a group of 111 confirmed SARS patients between March 10, 2003 and June 18, 2003. Both CT and TTM are used on the same patient in diagnosis and monitoring. We conclude that TTM is able to depict the position, morphology, and progress of lesions with the same degree of success as CT. The combination of CT and TTM can improve the quality and accuracy of SARS diagnosis. PMID- 17271527 TI - The study about the temperature distribution of the sphere medium surface. AB - The medical examinations by the infrared ray are used to examine some illnesses, and they are not harmful to us. The body surface is considered as the plane in the examinations, but the parts of our bodies are the curved surfaces and the results are more exact when we consider the bodies as the curved surfaces. The sphere is the most simple curved surface so we studied the sphere medium interface, the heat radiation temperature distribution of the sphere medium based on the experiments and put forward the theory to explain the temperature distribution. We hope to give the supplement for the earlier research through our research. PMID- 17271528 TI - Fundamental theoretic research of thermal texture maps I--simulation and analysis of the relation between the depth of inner heat source and surface temperature distribution in isotropy tissue. AB - Thermal texture maps is a new technology that can locate the inner abnormal heat sources of human by thermography analysis, and a great deal of application examples in clinic to early detect breast cancer with it shows its effectiveness. But the current explanation for its principle is hard to comprehensive and did not illuminate clearly the relation between the inner heat source and surface temperature distribution. In this paper, the temperature fields caused by the point heat source in isotropy tissue are simulated in different conditions, including different heat source intensities, different heat transfer coefficients and different heat depths and so on. The variation of surface temperature with the heat source depth change is discussed especially. The analysis result of simulation data shows that there lies the special relation between the heat source depth and the surface temperature distribution. PMID- 17271529 TI - A circuit simulating method for heat transfer mechanism in human body. AB - It is a complicated process to produce the inner body heat and transfer the thermal energy to body surface. Based on the comparison between bio-heat transfer and current flow in circuit, this paper offers a method to analyze heat transfer mechanism using cold water to stimulate the body system to produce echo, and applying electrical components to build a circuit to simulate the process. This method considers the production of inner heat source, the influence of organism medium during inner thermal energy transfer to the body surface and the environment temperature. It is a primary attempt to evaluate the distribution of inner body temperature noninvasively by means of thermographs and provides a new way to analyze bio-heat transfer. PMID- 17271530 TI - Study of trilogy-imaging characteristics on TTM and its relationship with malignancies. AB - To study trilogy-imaging characteristics of thermal texture mapping (TTM) and its relationship with malignancies. TTM scanning was performed on 32 normal volunteers and 90 cancer patients who were included in this study. And the trilogy-imaging characteristics were observed. The percent of the characteristics of trilogy imaging on TTM is higher in cancer patients than normal control, P = 0.0000. In normal volunteers who have trilogy characteristics, the percent of the people with cancer family history was obviously higher than those without, P = 0.0003. Trilogy-imaging characteristics on TTM are correlated with the patients with malignancy or the normal people with cancer family history. Neuroendocrine immunology thesis might be the underlying mechanism of that phenomenon. PMID- 17271531 TI - Re-investigation of the mechanism of trilogy imaging characteristics on TTM in cancer patients. AB - According to neuro-endocrine-immune theory, we have done research and tried to find possible explanations of the relationship of trilogy imaging characteristics of thermal texture mapping (TTM) and patients with the malignancies, or the patients susceptible to malignancies. We performed another two experiments to study mechanism of trilogy imaging characteristics, however, the result was not as expected. We have to reconsider the relationship between 3 tumor platforms and hypothalamus-thyroid-pancreas. Is there any possible mechanism?. PMID- 17271532 TI - Evaluation of low-intensity laser external radiotherapy through thermal texture mapping (TTM) technology. AB - This paper aims to evaluate the curative effects of low-intensity laser external radiotherapy through thermal texture mapping (TTM) technology. The influences of 30 min nasal cavity irradiation of semiconductor laser (650 nm, 5 mW, continuous wave) on microcirculation were investigated through TTM. At the same time, with the aid of TTM, the influences of the irradiation on the whole body thermal balances and the functions of the liver and kidney were also studied. Altogether, 32 cases of microcirculation depression were investigated. After the 30 min nasal cavity irradiation, the total efficiency of microcirculation reached 100%. The effective ratio kept 96.9% 30 minutes later but the effect almost disappeared completely 150 minutes after the irradiation. No ill influence on the whole body thermal balance or metabolic functions of liver and kidney was found. Low intensity laser external radiotherapy was a promising therapy to improve microcirculation. TTM was the ideal evaluation technology promoting this therapy. PMID- 17271533 TI - Coherent backscattering spectroscopy: a new technique for tissue diagnosis. AB - Coherent backscattering (CBS) is a photon weak-localization phenomenon that gives rise to an enhanced backscattering of light by random media. This effect has been previously investigated using coherent light sources. Here we show that CBS can be observed using broadband low-coherence light. We demonstrate, for the first time to the best of our knowledge, that low-coherence detection substantially simplifies CBS measurements in biological tissue and enables depth-resolved spectroscopic analysis of CBS. CBS spectroscopy may find important applications in probing random media such as biological tissues where depth-selective measurements are crucial. PMID- 17271534 TI - Development of a fast scanning miniature probe and methods of dispersion management for high-resolution optical coherence tomography. AB - We present a design of a miniature fiber-optic probe capable of rapid lateral scanning. The miniature probe permits forward-looking optical coherence tomography (OCT) imaging of internal organs in real time. Fast lateral scanning also enables a new real-time image acquisition sequence, potentially permitting real-time focus tracking. To perform sensitive heterodyne detection, a sufficient Doppler frequency is achieved by using an electro-optic (EO) phase modulator. In this paper we describe an effective approach to compensate the dispersion induced by the EO crystal up to the third order. We show that an optimal axial resolution offered by the light source can be recovered through the dispersion management. Preliminary results of real-time OCT imaging of biological tissues with the lateral-priority scanning probe are presented. PMID- 17271535 TI - Molecular imaging of carcinogenesis with immuno-targeted nanoparticles. AB - Molecular characterization of cancer could have important clinical benefits such as earlier cancer detection based on molecular characterization, the ability to predict the risk of cancer progression, real time margin detection, the ability to rationally select molecular therapy and to monitor response to the therapy. We present a new class of molecular specific contrast agents for optical imaging of carcinogenesis in vivo - gold nanoparticles conjugated with monoclonal antibodies specific for cancer biomarkers. PMID- 17271536 TI - Visualizing early frog development with motion-sensitive 3-D optical coherence microscopy. AB - A motion-sensitive en-face-scanning 3-D optical coherence microscope (OCM) has been designed and constructed to study critical events in the early development of plants and animals. We describe the OCM instrument and present time-lapse movies of frog gastrulation, an early developmental event in which three distinct tissue layers are established that later give rise to all major organ systems. OCM images constructed with fringe-amplitude data show the mesendoderm migrating up along the blastocoel roof, thus forming the inner two tissue layers. Motion sigma data, measuring the random motion of scatterers, is used to construct complementary images that indicate the presence of Brownian motion in the yolk cells of the endoderm. This random motion provides additional intrinsic contrast that helps to distinguish different tissue types. Depth penetration at 850 nm is sufficient for studies of the outer ectoderm layer, but is not quite adequate for detailed study of the blastocoel floor, about 500 to 800 mum deep into the embryo. However, we measure the optical attenuation of these embryos to be about 35% less at 1310 nm. 2-D OCT images at 1310 nm are presented that promise sufficient depth penetration to test current models of cell movement near the blastocoel floor during gastrulation. PMID- 17271538 TI - Second harmonic optical coherence tomography. AB - Second harmonic optical coherence tomography, which uses coherence gating of second-order nonlinear optical response of biological tissues for imaging, is described and demonstrated. PMID- 17271537 TI - Pulse shaping strategies for nonlinear interferometric vibrational imaging optimized for biomolecular imaging. AB - Nonlinear interferometric vibrational imaging (NIVI) measures the temporal cross correlation of anti-Stokes radiation from coherent anti-Stokes Raman scattering (CARS) processes to achieve increased sensitivity, stray light rejection, and nonresonant background rejection. Because the intensity of CARS radiation is proportional to the square of the molecular density of a target resonance, it is critical to maximize the recoverable signal for a given illumination level. Especially if one desires to measure several resonances, there can be a sensitivity as well as a speed advantage to measuring them simultaneously rather than serially. We discuss the methods of sample excitation that NIVI allows and their potential sensitivity advantages, as well as present experimental results demonstrating Raman signal recovery using these pulse sequences. PMID- 17271539 TI - High-resolution ultrasound-aided biophotonic imaging. AB - Optical contrast is sensitive to functional parameters, including the oxygen saturation and total concentration of hemoglobin, in biological tissues. However, due to the overwhelming scattering encountered by light in tissues, traditional optical modalities cannot provide satisfactory spatial resolution beyond the ballistic (a few hundred microns) and quasiballistic (1-2 mm) regimes. Photoacoustic tomography is based on the high optical contrast yet utilizing the high ultrasonic resolution. Our work in this emerging area of research will be summarized in this invited talk. In this technology, a diffraction-based inverse source problem is solved in the image reconstruction, for which we developed the rigorous reconstruction theory. We implemented a prototype and accomplished noninvasive transdermal and transcranial functional imaging of small-animal brains in vivo. Change in the cerebral blood oxygenation of a rat, as a result of the alternation from hyperoxia to hypoxia, was imaged successfully. PMID- 17271540 TI - Multimodal integration of EEG and functional magnetic resonance recordings. AB - In this paper, advanced methods for the modeling of human cortical activity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are reviewed. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from magnetic resonance images, multidipole source model, and regularized linear inverse source estimates. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed fMRI. PMID- 17271541 TI - MR current density and conductivity imaging: the state of the art. AB - Current density imaging (CDI) is an imaging technique that measures electrical current density distributions in a volume of material or tissue, which can be imaged using magnetic resonance imaging (MRI). Measurements of current density are obtained by applying an external current to the material/tissue during an MRI acquisition. The magnetic fields produced by the applied current are mapped onto the phase image of the MRI acquisition. The phase images are processed to compute the current density distribution. Performing CDI requires an MRI system, additional hardware, a modified pulse sequence (PSD) and data processing software. Greig C. Scott, Michael L.G. Joy and R. Mark Henkelman developed CDI in 1988 at the University of Toronto (Canada). The CDI Research Group is presently based at the University of Toronto and is supervised by the author. This paper describes the CDI technique, its applications by this and other groups and recently proposed methods for electrical conductivity imaging based on the technique. PMID- 17271542 TI - Three-dimensional electrocardiographic imaging. AB - We review our recent work on the development and evaluation of three-dimensional electrocardiographic imaging technology (3DEIT). Cardiac electrophysiological properties, including activation time and transmembrane potentials, are estimated from body surface ECG signals with the aid of a realistic geometry heart model in which electrophysiological a priori information is incorporated. We have conducted computer simulation studies to demonstrate the feasibility of imaging activation sequence throughout the three-dimensional myocardium, and localizing sites of origin of activation and arrhythmias using our 3DEIT approach. We will also review the pilot experimental studies in evaluating the 3DEIT approach in a patient with pacemaker and experimental animals with intracardiac recordings. Our promising results to date suggest the feasibility of the 3DEIT technology that we are developing and that it merits further investigation. PMID- 17271543 TI - Simultaneus prediction of four kinematic variables for a brain-machine interface using a single recurrent neural network. AB - Implementation of brain-machine interface neural-to-motor mapping algorithms in low-power, portable digital signal processors (DSPs) requires efficient use of model resources especially when predicting signals that show interdependencies. We show here that a single recurrent neural network can simultaneously predict hand position and velocity from the same ensemble of cells using a minimalist topology. Analysis of the trained topology showed that the model learns to concurrently represent multiple kinematic parameters in a single state variable. We further assess the expressive power of the state variables for both large and small topologies. PMID- 17271544 TI - Neural interfacing. AB - The problem of interfacing microsystems to neurons or brain has led to exciting developments in the fields of micro/nanotechnologies and integrated circuitry and systems. Neurons have been patterned using micro/nanotechnologies to form structural and functional networks. Micro-electrodes and integrated circuitry have been developed for large scale, multichannel measurements from brain tissue. Driving force for this technology comes from research and clinical interest in the emerging fields of neural prosthesis, deep brain stimulations and brain machine interface. This review presents some examples of the work done in the field of neural patterning, tissue interfacing, electrodes, recording and system integration. PMID- 17271545 TI - Neural interfacing with the peripheral nervous system. AB - Although electrical stimulation has proven to be capable of restoring neuronal function in the damaged or injured nervous system, there are several limitations to this technique. The availability of electrodes capable of selective fascicle recruitment and physiological fiber diameter recruitment (from small to large) is crucial for the development of successful prostheses. Nerve cuff electrodes have several advantages over other methods since they can provide activation of multiple muscles groups from a single site. Current cuff electrodes are reshaping the nerve into round shapes and making it difficult to recruit selectively fibers in the center of the nerve. Yet two major problems have not yet found satisfactory solutions: 1) fascicle selectivity and fiber diameter selectivity. We present here a new design that reshapes the nerve into a flat configuration, the flat interface nerve electrode (FINE). This design can improve the ability of the electrode to selectively activate the various fascicles of the nerve. Experiments to measure this selectivity were carried out on the hypoglossal nerve and its three main branches. The ability to recruit various fascicles was estimated using a selectivity index (SI). The overall performance of the FINE, as defined by the selectivity index (SI), showed a high degree of selectivity at both the fascicular and muscular levels: 0.91 +/- 0.05 (n = 5) and 0.85 +/- 0.03 (n = 4), respectively. This flat interface design minimizes the maximum distance between each contact and the fibers. Computer simulation have shown that it is possible to reverse the recruitment order by using electrode arrays placed along the nerve. This model prediction was tested in the lateral gastrocnemius/soleus branch of the sciatic nerve in cats since these muscles are innervated by fibers with different diameters. A stimulus electrode was placed around LG nerve. Tendons of LG and soleus muscles were separated and attached to two independent force transducers. The recruitment curves generated by tripolar and array electrodes were compared. Tripolar stimulation recruited LG before soleus muscles as expected, whereas the electrode array fully activated soleus while activating only 50% of LG muscles. These results show that the electrode - array is capable of reversing the recruitment order by manipulating the extracellular voltage along the nerve. PMID- 17271546 TI - Functional near-infrared neuroimaging. AB - Functional near-infrared (fNIR) spectroscopy is a wearable neuroimaging device that enables the continuous, non-invasive, and portable monitoring of changes in blood oxygen and blood volume related to human brain function. Over the last three years, studies in the laboratory and under field conditions have established the positive correlation between a participant's performance and oxygenation responses as a function of task load. Our findings indicate that fNIR can effectively monitor attention and working memory in real-life situations. These experimental outcomes compare favorably with functional magnetic resonance imaging (fMRI) studies, and in particular, with the blood oxygenation level dependent (BOLD) signal. The capacity to monitor brain hemodynamics with a wearable device holds promise for the use of fNIR in the creation of a symbiotic relationship between the user and his/her everyday environment. Moreover, under operational conditions, the fNIR system is amenable to integration with other established physiological and neurobehavioral measures, including EEG, eye tracking, pupil reflex, heart rate variability, respiration and electrodermal activity. PMID- 17271547 TI - Patterning to influence in vitro neuronal interfaces. AB - Microlithographic techniques applied to control surface chemistry can be used to guide neurons to surface electrodes in in vitro culture. Here we report on the effectiveness of these techniques as measured by the likelihood of recording electrical signals and detecting propagation of network activity. PMID- 17271548 TI - Computation within cultured neural networks. AB - In this paper we present three related areas of research we are pursuing to study neural computation in vitro. Rat cortical neurons cultured on 60 channel multielectrode array (MEA) allow the researcher to measure from and stimulate sixty different sites across a small population of neurons grown in vitro. Using this system we can send stimulation patterns into the network and study how these living neural networks compute by measuring its outputs. Our first series of studies uses chaotic control techniques to study the dynamics and potentially control the behavior of cortical network. At the same time, we are beginning to apply a model of computation called the liquid state machine or LSM model developed by Wolfgang Maass to provide a firm mathematical framework from which to proceed with our investigations. Each of these components is integrated into a third area investigating the role of computation and feedback using a real-time sensory-motor feedback robotic flight system. PMID- 17271549 TI - Implantable neural probe systems for cortical neuroprostheses. AB - Advanced microfabrication processes, biomaterials, and systems technologies are enabling progressively more sophisticated devices to interface with the brain. In particular, microscale implantable neural probe systems have been developed to reliably stimulate and/or record populations of neurons for long periods of time. Our group has developed a silicon-based probe technology is effective for recording neural activity from neuronal populations for sustained time periods. In a recent study in rats, these probes consistently and reliably provided high quality spike recordings over extended periods of time. These probes are being used to investigate and develop cortical neuroprostheses and brain-machine interface systems. This neural probe technology is currently being extended to include polymer substrates, chemical interfaces for drug delivery, advanced coatings for improved biocompatibility, and integrated electronics for wireless communication to the outside world. PMID- 17271550 TI - Multisite microelectrode arrays for measurements of multiple neurochemicals. AB - Multisite microelectrode arrays designed for electrochemical measures of neurochemicals in CNS tissues are presented. The arrays have platinum recording sites insulated with polyimide on a ceramic substrate. Most designs include 4 recording sites, however arrays with 5 to 8 recording sites have been fabricated. Enzyme coatings have been developed to measure glutamate, choline, lactate, and glucose. Electroactive compounds such as dopamine, norepinephrine, and O/sub 2/ can also be measured. The multiple recording sites can be exploited for interferent or noise removal and measures of multiple compounds using a single microelectrode array. PMID- 17271551 TI - Recording advances for neural prosthetics. AB - An important challenge for neural prosthetics research is to record from populations of neurons over long periods of time, ideally for the lifetime of the patient. Two new advances toward this goal are described, the use of local field potentials (LFPs) and autonomously positioned recording electrodes. LFPs are the composite extracellular potential field from several hundreds of neurons around the electrode tip. LFP recordings can be maintained for longer periods of time than single cell recordings. We find that similar information can be decoded from LFP and spike recordings, with better performance for state decodes with LFPs and, depending on the area, equivalent or slightly less than equivalent performance for signaling the direction of planned movements. Movable electrodes in microdrives can be adjusted in the tissue to optimize recordings, but their movements must be automated to be a practical benefit to patients. We have developed automation algorithms and a meso-scale autonomous electrode testbed, and demonstrated that this system can autonomously isolate and maintain the recorded signal quality of single cells in the cortex of awake, behaving monkeys. These two advances show promise for developing very long term recording for neural prosthetic applications. PMID- 17271552 TI - System theory in industrial patient monitoring: an overview. AB - Patient monitoring refers to the continuous observation of repeating events of physiologic function to guide therapy or to monitor the effectiveness of interventions, and is used primarily in the intensive care unit and operating room. Commonly processed signals are the electrocardiogram, intraarterial blood pressure, arterial saturation of oxygen, and cardiac output. To this day, the majority of physiologic waveform processing in patient monitors is conducted using heuristic curve fitting. However in the early 1990s, a few enterprising engineers and physicians began using system theory to improve their core processing. Applications included improvement of signal-to-noise ratio, either due to low signal levels or motion artifact, and improvement in feature detection. The goal of this mini-symposium is to review the early work in this emerging field, which has led to technologic breakthroughs. In this overview talk, the process of system theory algorithm research and development is discussed. Research for industrial monitors involves substantial data collection, with some data used for algorithm training and the remainder used for validation. Once the algorithms are validated, they are translated into detailed specifications. Development then translates these specifications into DSP code. The DSP code is verified and validated per the Good Manufacturing Practices mandated by FDA. PMID- 17271553 TI - Continuous measurement of cardiac output using stochastic system identification techniques. AB - Indicator dilutions techniques offer the most reliable methods of determining clinical cardiac output because of the elastic nature of the cardiac vessels. A catheter-mounted beating filament affords a simple means of supplying "heat" indicator, but is power and temperature limited because of possible patient injury. A stochastic signal processing method using pseudorandom binary infusion of heat offers a process of enhancing the signal to noise sufficiently to facilitate a computation of cardiac output over a reasonable time period (5 min) with a clinically acceptable error. PMID- 17271554 TI - Adaptive filtering and alternative calculations revolutionizes pulse oximetry sensitivity and specificity during motion and low perfusion. AB - Pulse oximetry, utilizing spectrophotometric principles and normalized absorption of red and infrared light, provides vital information concerning patients' arterial oxygen saturation, pulse rate and perfusion level. Conventional pulse oximeters, incorporating conventional filters, are hampered by artifact interference from motion, electrical and ambient light and other conditions producing weak signals. Masimo introduced mathematically and physiologically based designs along with adaptive filtering and what it calls DST (Discrete Saturation Transform) as a solution to monitoring patients even during times of severe and unpredictable noise interference. This combined with 4 other alternative calculations, revolutionized pulse oximetry performance. This new technology is called Signal Extraction Pulse Oximetry or Masimo SET pulse oximetry. Sensitivity and specificity of signal extraction technology, was first tested extensively in the lab on volunteers under conditions designed to simulate varying physiology, including controlled desaturations, combined with severe patient motion, and low perfusion conditions. Conventional pulse oximeters demonstrated very low sensitivity and specificity while pulse oximeters with SET showed sensitivity and specificity of over 95% under the same conditions. Clinical testing was then performed on an extensive variety of patients in the hospital environment demonstrating similar performance, validating the significant advance resulting from the use of SET. False alarms due to motion artifact and low perfusion have been reduced from up to 90% to less than 5%. PMID- 17271555 TI - Proposed framework to measure the ROI of mobile tele-health solutions in the management of chronic diseases. AB - Significant changes in the distribution of healthcare costs (away from critical care and towards chronic diseases) pose major challenges to existing healthcare systems. Caring for a patient with a chronic disease lasts as long as a person is alive, and medical expenses accumulate unrelentingly. Therefore, new approaches to disease management of chronic diseases are urgently needed, especially in terms of increasing the (currently low) rate of adherence to the patient's prescribed treatment plan. A proposal is advanced to use mobile tele-health systems to enhance the effectiveness of disease management programs. A framework to measure the ROI (return on investment) of these systems is also proposed. PMID- 17271556 TI - Advances in robotic tele-echography services--the OTELO system. AB - This paper presents some of the recent advances in mobile robotic tele-echography systems. It discussed the feasibility of a reliable remote ultrasound examination using such robotic systems in wireless environments. That is to say, to make use emerging wireless communications to provide a medical expert or consultant the ability to examine a remote patient. A critical issue of such systems is the accurate interactivity between both remote sides. The paper presents a robotic teleoperated OTELO (mobile tele-echography using an ultra-light robot) system for such purposes. The paper presents an overview of the system and some of preliminary tests and the use of wireless communication in this e-health application. PMID- 17271557 TI - Delivering low-bandwidth telemedicine services over hybrid networks in developing countries. AB - The results of medical specialist consultations sampled from several rural clinics located throughout India indicate that remote expert opinions can improve the speed and accuracy of diagnosis. Central to this presentation is a description of how real-time and store & forward telemedicine services can be provided to rural populations over hybrid networks made up of ISDN, POTS, VSAT, cellular, and Cable Internet connections. A model for meeting the specialized medical needs of developing countries will be highlighted. Descriptions, examples, and benefits of how Browser-based client-server architectures are being used in over 20 locations in India and Mexico for triaging real-time vital signs, DICOM images, audio & video, and clinical text information will be highlighted. PMID- 17271558 TI - Cable-free wearable sensor system using a DC powerline body network in a conductive fabric vest. AB - A wearable DC powerline communication (PLC) network for health monitoring and rehabilitation is proposed. The network infrastructure is based on a novel use of conductive fabrics as the electrical transmission medium. Whereas other wearable networks rely on bulky sensors and cables, we combine PLC technology and intelligent sensor design to create a noninvasive, comfortable, flexible, and washable monitoring network. Additionally, the design allows us to incorporate multiple nodes in a single network. The network consists of three components; sensor nodes that are composed of a sensor, microprocessor, and local amplifier, a 'central' node that provides power to and processes information from the various sensor nodes in the network, and a two conductive sheets as the medium for power and data transmission. Using this medium, we can collect and record biological data from multiple sensor nodes to monitor the user's state. We will begin by reviewing a novel DC PLC network. Next, we will discuss the design of the conductive fabric vest and its salient features. Finally, we will present results of our initial experimental results and the future plans for this work. PMID- 17271559 TI - Development of reusable and expandable communication for wearable medical sensor network. AB - To meet the various communication requirements of the wearable medical sensor network, the reusable and expandable wireless communications platform has been developed. The connection between the central monitoring unit and the sensors around the body is implemented using the Bluetooth technology. And the data can be uploaded and downloaded to an external Internet server by the CDMA modem or Bluetooth LAN access point (LAP). The system used PDA as a central monitoring unit which records and displays the data received. PMID- 17271560 TI - Wearable medical devices for tele-home healthcare. AB - The world's ageing population and prevalence of chronic diseases have lead to high demand for tele-home healthcare, in which vital-signs monitoring is essential. An overview of state-of-art wearable technologies for remote patient monitoring is presented, followed by case studies on a cuffless blood pressure meter, ring-type heart rate monitor, and Bluetoothtrade mark-based ECG monitor. Aim of our project is to develop a tele-home healthcare system which utilizes wearable devices, wireless communication technologies, and multisensor data fusion methods. As an important part of this system, a cuffless BP meter has been developed and tested on 30 subjects in a total of 71 trials over a period of five months. Preliminary results show a mean error (ME) of 1.82 mmHg and standard deviation of error (SDE) of 7.62 mmHg in systolic pressure; while ME and SDE in diastolic pressure are 0.45 mmHg and 5.27 mmHg, respectively. PMID- 17271561 TI - Extracting breathing rate information from a wearable reflectance pulse oximeter sensor. AB - The integration of multiple vital physiological measurements could help combat medics and field commanders to better predict a soldier's health condition and enhance their ability to perform remote triage procedures. In this paper we demonstrate the feasibility of extracting accurate breathing rate information from a photoplethysmographic signal that was recorded by a reflectance pulse oximeter sensor mounted on the forehead and subsequently processed by a simple time domain filtering and frequency domain Fourier analysis. PMID- 17271562 TI - Digital microfluidics for bioassays and drug delivery. AB - This presentation will focus on the development of microscale and nanoscale platform technologies for the interrogation and manipulation of biological and physiological activities. One platform we are developing can generate micro and nanoscale droplets/particles/vesicles by controlling amphiphilic interfaces in microfluidic devices. I utilize self-assembly forces in nature to design nanoscale structures that interface biological components with physical transducers that interrogate their activities or allow external manipulation. Through the design of microfluidic channel networks, droplet arrays present a novel method for controlling biochemistry and self-assembly at picoliter to femtoliter volumes, approaching the level of cellular activities. Nanoscale features can be designed into these vesicles that mimic biological functions such as molecular recognition, protein synthesis, and molecular transport. Based on the materials delivered, droplets can then form polymer nanoparticles (e.g. photopolymerization), lipid bilayer vesicles, and multilayer drug particles. Applications that we are pursuing include smart vesicles for targeted imaging and therapeutics for cardiovascular diseases, synthetic antibodies by molecular imprint polymer nanoparticles, protein crystallization, quantum dot synthesis in droplet microreactors, combinatorial cell-based assays, and cell-encapsulation for combinatorial assays and tissue engineering. PMID- 17271563 TI - The need for cellular and molecular sensors and actuators. AB - Systems biology may present the ultimate micro- and nanoengineering challenge: a single mammalian cell requires at least a hundred-thousand variables and equations to describe its dynamic state, cell-cell interactions are critical to system function, and some organs have a billion interacting cells. At present, biologists might record five dynamic intracellular variables simultaneously from a single cell--typically through fluorescent imaging. Historically, the assumption has been that it is sufficient to hold all but a few variables constant and make a limited number of measurements. In a realm of highly interconnected, distributed nonlinear networks, measurements made in this way cannot adequately capture system dynamics. The growing interest in nanobiology and nanomedicine is spawning extensive activity in artificial nanosensors that include ligand-gated ion channels, fluorescent nanocrystal reporters that bind to targeted sites, nanofibers that can deliver DNA, and metal nanoshells that can provide localized heating. The engineering challenges that must be met for nanoscience to make a broad impact in basic research in biology and medicine include techniques to record and control multiple dynamic variables in single cells; nanosensors that report the local environment rather than just position; and addressable nanoactuators that control more than just conductance or temperature. PMID- 17271564 TI - Integrated microfluidic biochips for immunoassay and DNA bioassays. AB - Bioassays involve multi-stage sample processing and fluidic handling, which are generally labor-intensive and time-consuming. Using microfluidic technology to integrate and automate all these steps in a single chip device is highly desirable in many practical applications such as clinical diagnostic and in-field environmental testing. We have developed self-contained and fully integrated biochip systems for immunoassay and DNA analysis. These microfluidic biochip devices can perform detection of multiple bioagents (including antigens and DNA) using electrochemical detection methods. Microfluidic mixer, valves, pumps, channels, chambers, and Combimatrix microelectrode array are integrated to perform parallel immunoassays to detect infectious particles (viruses and bacteria) from complex biological samples in a single, fully automated biochip device. All microfluidic components use very simple and inexpensive approaches in order to reduce chip complexity. Back-end detection is accomplished using an enzyme-based electrochemical detection method that has many advantages including high sensitivity ( approximately fM) and simple apparatus. The sensor is a miniaturized array of individually addressable microelectrodes controlled by active CMOS circuitry. Pathogenic bacteria and DNA detections are both demonstrated. The devices with capabilities of on-chip sample processing and detection provide a cost-effective solution to direct sample-to-answer biological analysis for point-of-care genetic analysis, disease diagnosis, and in-field bio threat detection. PMID- 17271565 TI - Microdevices for biomolecular detection. AB - Our research focuses on using silicon microfabrication to develop quantitative, high throughput and realtime techniques for measuring biomolecular interactions. Over the last year, we have developed a new detection method where specific biomolecules adsorb to the walls of a suspended microchannel resonator and thereby lower its resonant frequency. Confining the fluid to the inside of the resonator significantly increases sensitivity by eliminating high damping and viscous drag. It also enables direct integration with conventional microfluidic systems and allows the resonator to be actuated by electrostatic forces. In this presentation, I will introduce the resonator, show recent progress towards achieving its fundamental limit of detection, and outline a path towards high throughput measurement for systems biology. PMID- 17271566 TI - Diagnostic potential of nonlinear analysis of biosignals. AB - Biosignals have played an important role in medical diagnosis. The first biosignal to be used extensively was the electrocardiogram whose interpretation initially relied on manual analysis of paper tracings. Interpretation was based on variations of the normal QRS pattern associated with each heartbeat. Automated arrhythmia analysis was developed commercially and has been in standard clinical use for some time. The advent of Holter monitoring presented new challenges for the analysis of very long time series. New methods have been developed for this purpose, including nonlinear dynamical approaches. These methods have yielded important diagnostic clues. In this article, the diagnostic use of parameters derived from nonlinear analysis, both alone and in conjunction with other clinical information, is discussed. PMID- 17271567 TI - Nonlinear methods for biopattern analysis: role and challenges. AB - An important trend in medical technology is towards support for personalised healthcare, fuelled by developments in genomic-based medicine. New computational intelligent techniques for biodata analysis will be needed to fully exploit the vast amounts of data that are being generated. Non-linear signal processing methods will form an important part of such computational intelligent techniques. This paper introduces some non-linear methods which are likely to play a role in the emerging area of biopattern and bioprofile analysis that will underpin personalized healthcare. We highlight their application to clinical problems involving EEG and fetal ECG and heart rate analysis, and issues that arise when they are applied to real world problems. The clinical problems include dementia assessment, drug administration and fetal monitoring. The potential role and challenges in the application of non-linear signal analysis of biopattern and bioprofile are highlighted within the context of a major EU project, BIOPATTERN. PMID- 17271568 TI - Nonlinear analysis of heart rate variability signal: physiological knowledge and diagnostic indications. AB - The complex structure of the heart rate variability signal (HRV) has been widely studied in order to identify the "complex" nature of its control mechanisms. By adopting methods based on the reconstruction of the HRV time series, in an embedding space, the fractal dimension and the Lyapunov exponents can be computed. These estimations must be associated to a determinism test based on surrogate data, confirming that it is a deterministic instead of a linear correlation mechanism that controls the HRV dynamics. Results in 24 hours HRV series confirm that the structure generating the signal is neither linear nor stochastic. Furthermore, methods quantifying fractal and self-similar "monofractal" characteristics (1/f/sup alpha/ spectrum, detrended fluctuation analysis, DFA) and a regularity statistic (approximate entropy, ApEn), allow characterizing the HRV signal and distinguishing pathological from healthy subjects. Results in the HRV signal analysis confirm the presence of a nonlinear deterministic structure in time series. Moreover, nonlinear parameters can be used to separate normal from pathological subjects. Application examples are shown concerning cardiovascular pathologies and fetal heart rate analysis. PMID- 17271569 TI - The evolution of CellML. AB - CellML is an open XML-based markup language for describing and exchanging mathematical models of biological processes. While CellML was originally designed to describe and exchange models of cellular and subcellular processes, the design principles that were applied to the construction of a language with this relatively narrow focus are equally applicable to the specification of a language with a much wider scope. In this paper we describe the structure of CellML, how the language is evolving to broaden its scope, and what tools are being developed to facilitate its use. PMID- 17271570 TI - The foundational model of anatomy: a template for the symbolic representation of multi-scale physiological functions. AB - We describe the foundational model of anatomy (FMA), reference ontology for the discipline of human anatomy. Using the semantic structure of the FMA as knowledge representation template, we propose a physiology reference ontology (PRO) as a corresponding ontology for "functional bioinformatics". We envision the PRO as a source vocabulary for building symbolic representations of human physiological states and actions that may ultimately be extensible to other species. We describe the evolving architecture of the PRO, in terms of simple examples based on the anatomical concepts encoded in the FMA. PMID- 17271571 TI - AFL and FRL: abstraction and representation for field interchange. AB - The holy grail of biomedical modelling is an integrated model of the entire human body. To this end, research groups around the world need to interchange experimental data, models and model results. A good interchange will have an efficient representation for storage and sharing and will have tools for modelling, data verification, authoring, data conversions and so on. A field is a spatially varying properly. In this paper we present the abstract field layer (AFL) and the field representation language (FRL). The AFL provides the field abstraction together with a set of common field operations. The FRL provides an efficient means for field representation and storage. We show how fields can be used to interchange information between modelling systems and between modelling and visualisation systems. We are currently developing a software system that composes multiple single cell solvers to create a tissue solver. PMID- 17271572 TI - Training strategies for the user interface of vocational assistive robots. AB - Two different user training strategies were tested on the ProVAR (professional vocational assistant robot) system. Test subjects were either trained on the full system or first separately on the graphical user interface (UI) alone, away from the robotic arm followed by training on the full system with both the UI and robotic arm. Beginning training separately from the robot allows an introduction to the system to be initiated earlier and at the location most convenient for the user. However this extra training time is not offset by a shortening of the total training time needed to master the system. The choice to do UI only training should be selected based on other motivations such as the desire to engage a potential user during mandatory bed rest, an often otherwise underutilized time. PMID- 17271573 TI - Radio frequency conductive keratoplasty in the cornea: prediction of diopter changes in numerical models. AB - Correction of hyperopia (far-sightedness) requires increasing the curvature of the cornea. Radio frequency (RF) current is presently being used to shrink corneal collagen at peripheral points and achieve the required correction in a procedure named "conductive keratoplasty". Finite difference method numerical models of the electric and current density fields, thermal fields, and resulting damage and collagen shrinkage fields have been created and used to study and quantify the effects of uncertainties in applied voltage and tissue impedance on results obtained from this process. PMID- 17271574 TI - Intra-operative RF ablation in the atria. AB - We examined two methods of creating atrial linear transmural lesions for an epicardial approach. In a monopolar approach, radiofrequency (RF) ablation was applied to a multiple coil electrode probe with internal cooling to create linear and transmural lesions from the epicardium. Compared to no cooling, internal cooling enables faster and deeper lesion formation. In vitro experiments showed that with internal cooling epicardial RF energy applications time requirements could be reduced from longer than 3 min to 45 seconds to achieve transmural lesions despite convective endocardial cooling produced by blood flow. In vivo experimentation in five sheep confirmed atrial transmural lesions were achieved using 120 seconds of RF application times at set temperatures of 80 degrees C. In a bipolar clamp approach, RF ablation was applied from multiple coil electrodes mounted on one jaw of the clamp to coil electrodes mounted on the opposing jaw of the clamp. In vitro experiments showed that lesions could be made reliably through tissues up to 1-cm thick using RF energy applied for 30 seconds with a set temperature of 80 degrees C. Animal experiments confirmed that pulmonary veins (PV) could be isolated in an electrophysiological (EP) sense from the left atrium by creating an encircling lesion in a cuff of tissue surrounding the PV using the bipolar ablating clamp technique. PMID- 17271575 TI - Hepatic radiofrequency ablation--an overview from an engineering perspective. AB - Radiofrequency (RF) ablation is receiving increasing attention as treatment for primary and metastatic liver cancer. RF ablation can be performed during open surgery, or minimally invasive through a small incision. An electrode is introduced into the liver tumor, and RF energy is applied. Tissue surrounding the electrode heats up, and is killed above approximately 50 degrees C, where tissue coagulation occurs. Ultrasound imaging is typically used to place the electrode, and monitor the ablation procedure; the exact dimension of the coagulation zone is not visible under ultrasound. Current devices can create coagulation zones between 4 and 7 cm diameter. For large tumors often multiple sequential applications are required, since current devices can only use a single electrode at a time. Current limitations include inadequate imaging modalities, uncontrolled shapes and size of coagulation zones, and inability to reach adequate temperatures close to large vessels. When future devices are available that improve upon these shortcomings, RF ablation may replace classical surgery as the standard treatment for liver cancer. PMID- 17271576 TI - Neurological manifestations of electrical trauma. AB - Some degree of neurological impairment is often found in patients following electrical injury. A wide range of neurological impairments can occur including peripheral neuropathies, chronic pain syndromes, brain injury and rarely severe paralytic syndromes. Outcome is difficult to accurately predict. The symptoms can present immediately or be delayed in onset. They can also be temporary, permanent or get progressively worse with time. The neurological impairment resulting from the current often comprises a substantial proportion of the morbidity associated with such injuries. It is known that electrical current can cause nerve injury, however, the primary etiology of such damage is yet to be elucidated. An unusual case of transient paralysis after high voltage burn associated with severe hypokalemia provides unique insight into a potential mechanism for nerve injury following electrical trauma. PMID- 17271577 TI - Stability of cellular proteins under supraphysiological temperatures. AB - We present quantitative analyses of the kinetics of cellular components confronted with the destabilizing effect of irreversible thermal denaturation. We examine the dependence of the thermal denaturation on the heating rate, relative stability, population and lifetime of the states involved in transition and crowding effects. We propose a mechanism for self-stabilization of proteins during unfolding in tightly packed fibers and membranes. Speaking in terms of vulnerability to thermal denaturation, our results suggest that the thermal alteration of the plasma membrane is likely to be the most significant cause of the tissue necrosis. PMID- 17271578 TI - Electroporation of a multicellular system: asymptotic model analysis. AB - Quantitative understanding of electroporation in a multicellular system has been limited. The transient aqueous pore theory describes electroporation as the stochastic formation of hydrophilic pores in the presence of an applied electric field. We have used an asymptotic model for local membrane electroporation in a transport lattice system model to predict effects of a electrical pulse on a didactic multicellular model. We show that pulses of amplitude 0.2 to 2 kV/cm and duration 100 micros can cause extensive electroporation resulting in significant redistribution of transmembrane voltages. PMID- 17271579 TI - Subcellular effects of nanosecond electrical pulses. AB - Electrical models for biological cells predict that reducing the duration of applied electrical pulses to values below the charging time of the outer membrane causes a strong increase in the probability for electric field interactions with intracellular structures. For electric field amplitudes exceeding MV/m such pulses are expected to cause electroporation of cell organelles, with the required electric field amplitude scaling linearly with the inverse of pulse duration. Experimental studies where human cells were exposed to pulsed electric field of up to 300 kV/cm amplitude with duration as short as 10 ns, have confirmed this hypothesis. The observed effects include the breaching of intracellular granule membranes without permanent damage to the cell membrane, abrupt rises in intracellular free calcium levels, and enhanced expression of genes. At increased electric fields, the application of nanosecond pulses induces apoptosis in biological cells, an effect that has been shown to reduce the growth of tumors. PMID- 17271580 TI - Magnetic resonance imaging of muscle electroporation injury. AB - Low frequency electrical currents traversing the body during electrical shock can produce tissue damage by effects of electrical forces on cellular organelles and proteins as well as by Joule heating beyond thermotolerance. Treatment for these different injuries are quite distinct. Therefore, it is important to accurately diagnose the form of injury. Here we discuss the use of MRI for this purpose. PMID- 17271582 TI - Biological engineering and systems biology--new opportunities for engineers in the pharmaceutical industry. AB - The consecutive life science revolutions of molecular biology and genomic biology have led to the promise for improving human health by molecular-level interventions--but the accompanying challenge of doing so in a rational, predictive manner. Addressing this challenge, and meeting this promise, requires understanding of complex biological processes with molecular detail but in integrative fashion; the emerging field aimed at this endeavor is now commonly termed 'systems biology'. In many ways, this field is an ideal application area for the biological engineering discipline, and offers tremendous opportunities for biology-based engineers. This talk will present a view of key aspects of this vision. PMID- 17271581 TI - Contribution of biomechanics to clinical practice in orthopaedics. AB - Biomechanics is a field that has a very long history. It was described in ancient Chinese and Greek literature as early as 400-500 BC. The foundation of biomechanics, however, was laid during a period between the 1500's to 1700's by renowned personalities, da Vinci, Galileo, Borelli, Hooke, Newton, and so (Fung, Y.C., Biomechanics: Mechanical Properties of Living Tissues, 2nd Ed. Springer Verlag, Chapter 1, 1993). Beginning in the 1950's, Muybridge, Steindler, Inman, Lissner, and Hirsch performed the pioneering work on musculoskeletal biomechanics and the foundation of orthopaedic biomechanics was formed. For the following two decades, the field has blossomed and significant contributions in the biomechanics of bone, articular cartilage, soft tissues, upper and lower extremities, spine and so on has been made. More sophisticated equipment, coupled with mathematical modeling and better engineering design, has enabled us to make great strides. Bioengineers, in collaboration with orthopaedic surgeons, have translated many laboratory discoveries into clinical practice, leading to improved patient treatment and outcome. In the past 30 years, my colleagues and I have focused our research on the biomechanics of musculoskeletal soft tissues, ligaments and tendons, in particular. Therefore, in this lecture, the function of knee ligaments, the associated homeostatic responses secondary to immobilization and exercise, and healing of the ligaments will be reviewed. Examples of scientific findings that help to guide the surgical management of injury to ligaments will be given. New ideas on functional tissue engineering to improve the healing of knee ligaments and tendons will be presented. We have learned that tendons and ligaments are indeed complex biological tissues. To fully understand their behavior, healing and remodelling processes, this author advocates major efforts be made to bring molecular biologists, morphologists, biochemists, bioengineers, physical therapists and clinicians to work together in a seamless manner to solve these complicated problems. As biomechanics is a field to study force and motion of the living, which includes molecules to cells to tissues to organs to the whole body, it has and will continue to be an integral part seeking solutions that will help injured patients to return to their sports activities more quickly and completely. PMID- 17271583 TI - Biomedical engineering: a field on the move. AB - Interest in biomedical engineering has grown explosively during the past several years. The primary causes are major advances in technology and biological understanding that have caught the imagination of students and young researchers. The Whitaker Foundation has contributed to the growth by encouraging talented individuals to enter the field, and by helping universities to offer high-quality educational programs in biomedical engineering. Although the Foundation will close in 2006, new funding opportunities, universal recognition of the benefits of interdisciplinary research and product development, and a pool of talented individuals continue to promise a bright future for the profession. PMID- 17271584 TI - Bioinformatics and computational systems biology: at the cross roads of biology, engineering and computation. AB - We are witnessing the emergence of the "data rich" era in biology. The myriad data in biology ranging from sequence strings to complex phenotypic and disease relevant data pose a huge challenge to modern biology. The standard paradigm in biology that deals with hypothesis to experimentation (low throughput data) to models is being gradually replaced by data to hypothesis to models and experimentation to more data and models. And unlike data in physical sciences, that in biological sciences is almost guaranteed to be highly heterogeneous and incomplete. In order to make significant advances in this data rich era, it is essential that there be robust data repositories that allow interoperable navigation, query and analysis across diverse data, and a plug-and-play tools environment that will facilitate seamless interplay of tools and data. Further, the integrated data will enable the reconstruction and modeling of biological systems. This talk with address several of the challenges posed by enormous need for scientific data integration and modeling in biology with specific exemplars and possible strategies. The issues addressed will include--Architecture of Data and Knowledge Repositories--Databases Flat, Relational and Object-Oriented; what is most appropriate? The imminent need for Ontologies in biology--Reduction and Analysis of Data the largest challenge! How to integrate legacy knowledge with data? How can we carry out systems level modeling in biology? PMID- 17271585 TI - Mechanobiology in intervertebral disc degeneration and regeneration. AB - The intervertebral disc is an avascular, pliant, composite structure that separates spinal vertebrae and, in health, serves to support compression and facilitate movement. Its morphological organization is directed by fluid pressure and consists of a central swelling gel (nucleus), surrounded peripherally by a constraining ligament (annulus fibrosus), and separated from adjacent vertebrae by semi-permeable membranes (endplate). These three tissues serve differing structural roles, are subjected to differing mechanical environments, and are composed of unique matrices and cells. Viewing disc cells as mechanosensors, we use in vivo models of disc loading to identify spatial and temporal relationships between stress/strain and cell function that define normal morphology and drive the architectural changes attributed to normal aging and degeneration. Intra discal stress patterns consistent with disc health can then be elucidated based on these relationships, and in turn, help us develop spine-loading criteria that parameterize injury tolerance. This same perspective is critical for tissue engineering approaches for disc repair. Cells and matrices meant to guide healing need to withstand the demanding mechanical forces in the acute phases, and differentiate/remodel along the appropriate trajectory in the long-term. Because of their unique potential for adaptation, we are exploring the mechanoplasticity of mesenchymal stem cells (MSCs) and their use in disc repair strategies. Our data demonstrate that these cells respond differentially to pressure and distortion, and can be delivered, retained, and survive in the disc's demanding mechanical/biochemical environment. Because of these features, MSCs are qualified as an intriguing autograft cell type for disc repair. PMID- 17271587 TI - School children dyslexia analysis using self organizing maps. AB - The main goal of the study is an unsupervised classification of school children dyslexia. Eye movements of 49 subjects were measured using videooculographic technique (VOG) during two non-reading and one reading tasks. A feature selection was performed obtaining data set consisting of 26 features. Next an inductive modelling technique was applied to data set resulting in extraction of six features which were used as the input to self-organizing map (SOM). Three clusters were finally formed by the SOM proving that the proposed methodology is suitable for automatic dyslexia analysis. PMID- 17271589 TI - Classification of single trial EEG during motor imagery based on ERD. AB - EEG-based brain computer interface (BCI) provides a completely new communication channel between human brain and computer. Classification of EEG signals is a difficult task, especially when the classification has to be preformed on a single-trial EEG to continuously control a device. Event related desynchronization (ERD) has proven to be induced on the contralateral sensorimotor area during imagination of a left or right hand movement. In this paper, we introduced a quantification of ERD, with which a lower classification error rate and a higher information transfer rate can be obtained. The performance was tested by the Graz dataset for BCI competition 2003. PMID- 17271590 TI - Respiratory sounds classification using cepstral analysis and Gaussian mixture models. AB - The Cepstral analysis is proposed with Gaussian Mixture Models (GMM) method to classify respiratory sounds in two categories: normal and wheezing. The sound signal is divided in overlapped segments, which are characterized by a reduced dimension feature vectors using Mel-Frequency Cepstral Coefficients (MFCC) or subband based Cepstral parameters (SBC). The proposed schema is compared with other classifiers: Vector Quantization (VQ) and Multi-Layer Perceptron (MLP) neural networks. A post processing is proposed to improve the classification results. PMID- 17271591 TI - A new quantitative analysis technique for cardiac arrhythmia using bispectrum and bicoherency. AB - Ventricular tachyarrhythmias, in particular ventricular fibrillation (VF), are the primary arrhythmic events in the majority of patients suffering from sudden cardiac death. Attention has focused upon these articular rhythms as it is recognized that prompt therapy can lead to a successful outcome. There has been considerable interest in analysis of the surface electrocardiogram (ECG) in VF centred on attempts to understand the pathophysiological processes occurring in sudden cardiac death, predicting the efficacy of therapy, and guiding the use of alternative or adjunct therapies to improve resuscitation success rates. Atrial fibrillation (AF) and ventricular tachycardia (VT) are other types of tachyarrhythmias that constitute a medical challenge. In this paper, a high order spectral analysis technique is suggested for quantitative analysis and classification of cardiac arrhythmias. The algorithm is based upon bispectral analysis techniques. The bispectrum is estimated using an AR model, and the frequency support of the bispectrum is extracted as a quantitative measure to classify atrial and ventricular tachyarrhythmias. Results show a significant difference in the parameter values for different arrhythmias. Moreover, the bicoherency spectrum shows different bicoherency values for normal and tachycardia patients. In particular, the bicoherency indicates that phase coupling decreases as arrhythmia kicks in. PMID- 17271592 TI - Comparing objective feature statistics of speech for classifying clinical depression. AB - Human communication is saturated with emotional context that aids in interpreting a speakers mental state. Speech analysis research involving the classification of emotional states has been studied primarily with prosodic (e.g., pitch, energy, speaking rate) and/or spectral (e.g., formants) features. Glottal waveform features, while receiving less attention (due primarily to the difficulty of feature extraction), have also shown strong clustering potential of various emotional and stress states. This study provides a comparison of the major categories of speech analysis in the application of identifying and clustering feature statistics from a control group and a patient group suffering from a clinical diagnosis of depression. PMID- 17271593 TI - Benign versus malignant classification of breast tumors based on the the PLSN model for the ultrasound RF echo and homomorphic filtering. AB - The Power-law Shot Noise (PLSN) model has been recently proposed for modeling the ultrasound radio-frequency echo. According to it, the spectrum of the in phase/quadrature/envelope components are power-law functions. The corresponding power-law exponents were shown to possess good tissue characterization ability. A crucial step in the computation of in-phase/quadrature/envelope components is the estimation of the echo center frequency at different depths. We here propose a robust way of estimating the center frequency. We employ a well known convolutive model for the rf echo that views the echo as convolution of the tissue response and a component that represents the combined effect of the ultrasound impulse response and frequency dependent attenuation. Via low-pass filtering in the cepstrum domain, the combined ultrasonic contribution and attenuation term is extracted and used to estimate the center frequency. Furthermore, the tissue contribution is used to construct two new tissue characterization features. ROC analysis of 65 clinical ultrasound images of the breast indicates that the proposed features combined yield an area of 0.963. PMID- 17271594 TI - Design of ECG-based anaesthesia monitor/pain monitor. AB - Design of Anaesthesia monitor/ Pain monitor, using ECG signal only, is presented in this paper. During surgical operations, ECG is picked-up as a routine procedure; the same ECG is used here, hence it is almost noninvasive. Initially heart rate variability (HRV) spectrum is obtained from R-R intervals (RRIs) and the respiratory peak is identified. Following the contour of this peak, a bandpass filter is designed using frequency sampling technique. The entire RRIs is then passed through this filter. The output contains the information about the respiratory cycles only and RSA (respiratory sinus arrhythmia) is obtained from it. It is assumed that, level of consciousness is proportional to RSA. Relaxation in the muscle is taken as overall relaxation of the body and parasympathetic dominance, as a measure of it, is obtained from the ratio of power in the respiratory and baroreceptor peaks. It is seen that the same instrument may be used as pain-monitor because unbalancing in the autonomic system (ANS) is also created during pain. A total of three dozen patients were tested, two dozens with anaesthetic drugs and the rest with thermal probe creating erythema. The results, in both the cases, are close to the expectation of the anaesthetists. PMID- 17271595 TI - Epileptic seizure detection from ECoG using recurrence time statistics. AB - A recurrence time statistics T1 is defined and used as a feature extraction method for seizure detection. The preliminary data shows that during seizure T1 generates a peak and this peak clearly distinguishes the seizure state from background activity. When applied to multi-channel ECoG recordings, the spatial temporal signature of T1 can be clearly observed to discriminate seizures. The T1 feature was used for automated seizure detection on two sets of long term monitoring ECoG data. The detection probability reached 97% with a 0.29 per hour average false alarm rate. PMID- 17271596 TI - Detection of K-complexes in sleep EEG using CD-HMM. AB - In the current paper a new approach for K-complex detection using a continuous density hidden Markov model (CD-HMM) is presented. The system performance was evaluated in two manners. First using three seconds long segments of K-complexes and of background EEG (classification problem). Second using a whole night record and detecting the K complexes (detection problem). The fist test achieved an equal error rate of 7%. In the second test the system performance was compared to four trained scores that scored the signal independently. The performance of the algorithm was within the variance of the human scorers. PMID- 17271597 TI - Wavelet based method for detection: application in proprioceptive rehabilitation. AB - After knee or ankle injury, Freeman has proposed a rehabilitation program consisting in a prolonged maintain of monopodal equilibrium on an unstable plateform. The efficacy of such programs, often debated, is evaluated in the present study by a quantification of equilibrium criteria and electromyographical activities along the rehabilitation program. Our aim is to detect all events in the four EMG signals of soleus, tibialis anterior, peroneus longus and vastus medialis muscles and then deduce the stability of the person. To achieve the detection in EMG, the signals are considered to be piecewise stationary, with no a priori knowledge of the parameters of the hypotheses on the process state to be detected. The detector is based on a combination of dynamic cumulative sum (DCS) and the detail coefficients obtained after the application of the Mallat's fast decomposition algorithm without reconstruction of the detail signals. The DCS detection algorithm is based on the recursive calculation of the local generalized likelihood ratios associated with a multi-scale decomposition using wavelet transform. Results show that there is a correlation between stability and the energy of EMG signals. PMID- 17271598 TI - Action potential detection with automatic template matching. AB - Detecting action potentials has an important role in analyzing extracellular neuronal recordings. Current algorithms require subjective tuning by a user in the form of user-specified parameters. This work describes a fully automatic template-matching spike detection algorithm that does not require any tuning. This algorithm is robust to noise and performs better than an optimum threshold detection algorithm. PMID- 17271599 TI - Model-based seizure detection method using statistically optimal filters. AB - In this paper, a model-based seizure detection method using statistically optimal filters (SONFs) is presented. A template seizure from a patient is first selected and the basis functions required by the SONF are derived from this template seizure using wavelet transform. Subsequent EEG (electroencephalogram) recording is processed by the SONF and the output represents the noise-free estimate of the seizure. The energy ratio between the output and the input of the SONF is calculated and used as the test statistic for the seizure detection. Experiments using the SEEG (stereoelectroencephalogram, or intracerebral EEG) recordings of two patients show that this is an effective and promising method, with the possibility of reduced false detections. PMID- 17271600 TI - Detection of movement artifacts in respiratory inductance plethysmography: performance analysis of a Neyman-Pearson energy-based detector. AB - In [3] we developed a method for the automated estimation of the phase relation between thoracic and abdominal signals measured by noninvasive respiratory inductance plethysmography (RIP). In the present paper, we improve on the phase estimator by including an automated procedure for the detection of periods of gross body movements. We assume that the number of sleep obstructive events during periods of gross body movements is zero in probability. We hope that combining the phase estimator with the gross body movement detector should yield improved diagnostic tools for the automated classification of obstructive hypopnea events. PMID- 17271601 TI - Conceptual design of a multi-functional sphygmus detection system. AB - From the energy point of view, obtaining simultaneous blood pressure and flow rate of the radial artery at the wrist is very important for sphygmic diagnosis in medicine. This work depicts the conceptual design for a noninvasive multi functional sphygmus detection system. According to Y. C. Fung's flow rate equation, flow rate is a function of the diameter of the blood vessel, two adjacent pressures, arterial compliance, the distance between the two adjacent pressures and the viscosity of the blood. Because the distance between the two adjacent pressures is preset and the viscosity is obtained from either a data bank or viscometer, four measuring techniques are proposed to realize the calculation of the flow rate. First, use thermal array sensors and a thermal image identification technique to locate the artery for positioning the sphygmus detection head at wrist and to estimate the diameter of blood vessel as well. Second, detect the delay time between the two adjacent pressures, and then compute the downstream pressure in accordance with the sampled upstream pressure and delay time. Third, employ pressure feedback control to determine the variation of the vessel diameter that in turn can be used to compute the dynamic arterial compliance. Finally, use the nonlinear flow rate equation to calculate the blood flow rate. PMID- 17271602 TI - Relationship of magnitude of electromyogram of the lumbar muscles to static posture. AB - This work reports research that investigated the relationship of the strength of contraction of different muscles of the lumbar back to maintain static posture. The paper reports the study of surface electromyogram of the muscles and uses scattering and neural networks on the strength of the EMG measured using root mean square (RMS). The signal is studied before and after the removal of electrocardiogram (ECG) artifact from the signal using a modified independent component analysis technique. The three dimensional scattering plots do not show any observable trends while the neural networks before the removal of ECG does not converge while after removal of ECG the neural network shows a high level of accuracy. The results demonstrate that there is a complex relation between the four EMG and posture and this relationship is revealed only after of ECG from EMG. PMID- 17271604 TI - Decomposition of electromyographic signals by iterative message passing in a graphical model. AB - The problem of decomposing electromyographic (EMG) signals is considered. Starting from a graphical model (factor graph) of the problem, a new iterative decomposition algorithm is proposed. It is based on the sum-product (or belief/probability propagation) algorithm and is able to decompose heavily superimposed single- and multi-channel signals. PMID- 17271603 TI - The tremor coherence analyzer (TCA): a portable tool to assess instantaneous inter-muscle coupling in tremor. AB - This paper proposes a novel system for pathological tremor study and diagnosis. The system described called TCA (tremor coherence analyzer) is based on a electronic device developed for wireless monitoring of physiological variables. The device uses Bluetooth technology to communicate. The proposed technique for pathological tremor analysis uses surface EMG signals. The EMG sensors are located on forearm muscles to measure muscular activity due to pathological tremor. The coherence function between these signals is calculated. The application of the coherence function allows to determine linear dependencies between two signals. PMID- 17271605 TI - Improved resolution of pulse superpositions in a knowledge-based system EMG decomposition. AB - We have improved the accuracy (sensitivity x specificity) of a knowledge-based system from 90% to well above 95% in decomposing complex EMG 3-channel data into its constituent motor unit action potential (MUAP) trains. The key to achieving this improvement is our use of a probabilistic framework for resolving pulse superpositions through the application of utility maximization at the suprasegmental level. PMID- 17271606 TI - Optimized Gaussian mixture models for upper limb motion classification. AB - This paper introduces the use of Gaussian mixture models (GMM) for discriminating multiple classes of limb motions using continuous myoelectric signals (MES). The purpose of this work is to investigate an optimum configuration of a GMM-based limb motion classification scheme. For this effort, a complete experimental evaluation of the Gaussian mixture motion model is conducted on a 12-subject database. The experiments examine algorithmic issues of the GMM including the model order selection and variance limiting. The final classification performance of this GMM system has been compared with that of three other classifiers (a linear discriminant analysis (LDA), a linear perceptron neural network (LP) and a multilayer perceptron (MLP) neural network) . The Gaussian mixture motion model attains 96.3% classification accuracy using four channel MES for distinguishing six limb motions and is shown to outperform the other motion modeling techniques on an identical six limb motion task. PMID- 17271607 TI - Automated and manufacturer independent assessment of the battery status of implanted cardiac pacemakers by electrocardiogram analysis. AB - According to international standards, cardiac pacemakers have to indicate the status of their batteries upon magnet application by specific stimulation patterns. The purpose of this study has been to assess whether this concept can be used as a basis for automated and manufacturer independent examination of the depletion level of pacemakers in the framework of a collaborative telemedical pacemaker follow-up system. A prototype of such a system was developed and tested in a real clinical environment. Electrocardiograms (ECGs) were recorded during magnet application and automatically processed to extract the specific stimulation patterns. The results were used to assign each signal a corresponding pacemaker status: "ok," "replace" or "undefined," based on the expected behavior of the devices as specified by the manufacturer. The outcome of this procedure was compared to the result of an expert examination, resulting in a positive predictive value of 100% for the detection of ECGs indicating pacemaker status "ok." The method can, therefore, be utilized to quickly, safely and manufacturer neutrally classify cases into the categories "ok" and "needs further checking," which - in a telemedical setting - may be used to increase the efficiency of pacemaker follow-up procedures in the future. PMID- 17271608 TI - Independent component analysis applied to the P600 component of event-related potentials. AB - The analysis of the P600 component of Event-related Potentials (ERPs) has attracted attention due to its relation to covert cognitive mechanisms, in connection to memory processes. The component may often be low-amplitude, compared to other components such as the P300. Independent component analysis (ICA) techniques have been successfully applied in ERP processing, in the framework of blind source separation (BSS) for unmixing recorded potentials into a sum of temporally independent and spatially fixed components. In the present work ICA was used for reconstructing averaged ERPs in the time window of the P600 component, selecting a subset of independent components' projections to the original electrode recording positions. The selection is based on two empirical criteria, selecting the projection that reconstructs a P600 nearest temporally to the original P600, or selecting the projection combination - up to a preselected maximum number of combined projections providing maximum reconstructed P600 amplitude. The techniques are tested on ERPs recorded from healthy subjects and psychiatric patients, notably improving the differentiation of the two groups, based on either the amplitude or the latency of the reconstructed P600 component, in comparison to results achieved using the original ERPs. PMID- 17271609 TI - The effect of data reduction by independent component analysis and principal component analysis in hand motion identification. AB - Both independent component analysis (ICA) and principal component analysis (PCA) were used in this study to evaluate their effects in data reduction in the hand motion identification using surface electromyogram (SEMG) and stationary wavelet transformation. The results indicate that both methods increase the number of training epochs of the artificial neural network. The unsupervised fast ICA reduces the number of SEMG channels from 7 to 4. However the hand motion identification rate using the reduced channels is significantly lower (p < 0.05). On the other hand, the PCA reduces the size of neural network by more than 70%. Moreover, the results of discrimination rate and neural network training epochs show no significant difference as compared to the results before PCA reduction. The result of this study demonstrates that using wavelet and PCA are effective pre-processing for surface EMG analysis. It can efficiently reduce the size of neural network and increase the discrimination rate for different hand motions. PMID- 17271610 TI - Comparison between ICA and wavelet-based denoising of single-trial evoked potentials. AB - Analysis of evoked potentials (EPs) on a single-trial basis allows the study of the dynamical characteristics of brain activity. However, single-trial responses are buried into the more prominent ongoing electroencephalographic (EEG) activity, and thus advanced procedures are needed to obtain the activity only of the cortical generators that are activated by the experimental task under study. We compare the effectiveness of two methods at removing extraneous activity from single-trial EPs, namely, a recently-proposed iterative procedure based on independent component analysis (ICA) and wavelet denoising, using simulated data and actual EP recordings from normal subjects, more specifically the auditory N100-P200 complex. PMID- 17271611 TI - Evaluation of a BSS algorithm for artifacts rejection in epileptic seizure detection. AB - A data efficient blind sources separation (BSS) algorithm has been applied to preprocess intracranial EEG (ECoG) for artifact rejection. After artifacts correction a recurrence time statistics T1 feature was evaluated from the 'cleaned' data. Seizure detection performance was compared between BSS preprocessing and without preprocessing. Test results show that in a data set, for a detection rate of 96%, the false alarm rate dropped from 0.13 per hour without BSS preprocessing to 0.08 with preprocessing. For the other set of data, the false alarm rate dropped from 0.34 to 0.21 at a detection rate of 100%. PMID- 17271612 TI - Blind source separation of nerve cuff recordings. AB - Electrical stimulation of peripheral nerves can be used to restore partial motor function to individuals with neurological impairment. Previous work from our lab has shown that the flat interface nerve electrode (FINE) can be used to selectively stimulate fiber populations within a nerve trunk. We expect that selective recording of spatially segregated axon populations may also be possible with the FINE. The purpose of this modeling study was to assess the feasibility of using blind source separation (BSS) of the neurograms recorded with the FINE to distinguish signals from independent fascicles. We show that BSS is useful for identifying independent fascicular signals. Further, we introduce a simple post BSS processing method that resolves the inherent permutation ambiguity of BSS, and allows the BSS-estimated signals to be deterministically related to the appropriate corresponding fascicles. PMID- 17271614 TI - An approximate method for Bayesian entropy estimation for a discrete random variable. AB - This article proposes an approximated Bayesian entropy estimator for a discrete random variable. An entropy estimator that achieves least square error is obtained through Bayesian estimation of the occurrence probabilities of each value taken by the discrete random variable. This Bayesian entropy estimator requires large amount of calculation cost if the random variable takes numerous sorts of values. Therefore, the present article proposes a practical method for calculating an Bayesian entropy estimate; the proposed method utilizes approximation of the entropy function by a truncated Taylor series. Numerical experiments demonstrate that the proposed entropy estimation method improves estimation precision of entropy remarkably in comparison to the conventional entropy estimation method. PMID- 17271615 TI - A stochastic method for generating signals with jointly specified probability mass, spectral, and correlation properties for the identification of physiological systems. AB - An efficient stochastic interchange method was developed that allows two discrete time sequences to be created with a specified cross-correlation function and individually defined amplitude and spectral characteristics. The technique is particularly useful for creating sequences for the stimulation of multi-input physiological systems. It is very general in that sequences of any signal type can be manipulated and are not limited to being white and/or uncorrelated. By temporally separating occurrences of common frequencies, the method can even be used to create sequences that share common power, but can be treated as uncorrelated. The method is made practical by an algorithm that updates efficiently the auto- and cross-correlation functions of the sequences as they are being created. PMID- 17271616 TI - On 3D world perception: towards a definition of a cognitive map based electronic travel aid. AB - This paper addresses a 3D world perception principle and their usage for cognitive map building by visually impaired people. These bases are applied to define a new electronic travel aid named intelligent glasses system (IGS), a wearable system. IGS provides to blind people an information on their nearest 3D environment structure, and especially a tactile stimulating cognitive map of the obstacles located in user's peri-personal space. This paper outlines briefly the IG system, and presents first results on the validation of the proposed representation via psycho-physiological experiments. PMID- 17271618 TI - Analysis of respiratory and muscle activity by means of cross information function between ventilatory and myographic signals. AB - Analysis of respiratory muscle activity is a promising technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Evaluation of interactions between muscles is very useful in order to determine the muscular pattern during an exercise. These interactions have already been assessed by means of different linear techniques like cross-spectrum, magnitude squared coherence or cross-correlation. The aim of this work is to evaluate interactions between respiratory and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF), and finding out what information can be extracted from it. Some parameters are defined and calculated from CMIF between ventilatory and myographic signals of three respiratory muscles. Finally, differences in certain parameters were obtained between OSAS patients and healthy subjects indicating different respiratory muscle couplings. PMID- 17271617 TI - Stationarity study of the myoelectrical signal recorded from small bowel. AB - Electroenterogram (EEnG) is the myoelectrical signal recorded from small intestine. Due to the relationship between mechanical activity and myoelectrical activity of the intestinal smooth muscle, EEnG could be a solution for quantifying intestinal motility. Motility indexes are traditionally calculated from 1-minute window analysis. However, no prior works have analyzed whether signal properties remain constant or not within this time interval. The aim of present paper is to study time evolution of changes in EEnG spectrum in order to determine if traditional analysis and window length is satisfactory from the signal dynamics point of view. Mechanical and electrical activities are recorded simultaneously in bowel rings (at duodenum, angle of Treitz and jejunum) of three Beagle dogs. Thirteen recording sessions were carried out. A stationary index (SI) based on statistical analysis of time evolution of spectral parameters is defined and calculated over EEnG recording sessions. Results show that myoelectrical signal from bowel muscle is stationary during quiescence periods and maximum contractions periods. However, during irregular contractile activity (i.e. transitions from no-activity to maximum activity, or in fed state) electroenterogram is a non-stationary signal if 1-minute length is chosen for its analysis. Therefore, traditional intestinal motility indexes must be redefined using non-stationary techniques. PMID- 17271619 TI - Speech recognition methods applied to biomedical signals processing. AB - The paper focuses on processing of long biological signals used during monitoring procedures like in the case of portable Holter device for arrythmia analysis (ECG), intracranial pressure monitoring (ICP) in intensive care unit or overnight electroencephalogram monitoring (EEG) for sleep apnea detection. Two methods taken from speech processing are proposed: dynamic time warping (DTW) and hidden Markov models (HMM). The unsupervised analysis of ECG and ICP beats is carried out using hierarchical clustering approach. In case of EEG, first the estimation of sleep stages is performed and next the different breathing events are detected by HMM by means of Viterbi inference. We show that for the first two problems DTW outperforms HMM while in the third case the HMM inference capability makes HMM suitable for sleep apnea diagnosis. PMID- 17271620 TI - Regularized FOCUSS algorithm for EEG/MEG source imaging. AB - In this paper, we derived a generalized version of the regularized FOCUSS algorithm which was derived in [3]. It allows general forms of noise covariance and reduces depth effect when imaging focal neural sources from electroencephalography (EEG) / magnetoencephalography (MEG) data. We compared a depth-weighted regularized algorithm with FOCUSS and a regularized FOCUSS through simulation study. The suggested algorithm gave sparser and less spurious solutions than the others. PMID- 17271621 TI - Coherence estimation of the hippocampal EEG through fast multichannel orthogonal projection. AB - Hippocampal EEGs at subfields CA1 and the dentate gyrus (DG) are modeled as stationary, multi-channel autoregressive (MAR) process. This work discusses the development of a new MAR modeling algorithm that can efficiently compute MAR coefficient matrices through progressive multichannel orthogonal projection. The resultant MAR coefficients are least square (LS) optimal and utilized to compute the power spectra and the coherence function of hippocampal EEG at CA1 and DG during REM sleep for animals of 15 and 90 days of age. The results show that the new method is easy to implement and provides consistent and smooth spectral and coherence estimates for hippocampal EEG epochs with varying data length. PMID- 17271622 TI - A novel statistical model for simulation of arterial and intracranial pressure. AB - We describe a novel statistical model of pressure signals that incorporates the effects of respiration on arterial (ABP) and intracranial pressure (ICP). This model can be used to synthesize pulsatile ABP and ICP signals with similar time, frequency, and variability characteristics of real pressure signals. These synthetic signals can be used during the development, simulation, or quantitative assessment of biomedical algorithms in a variety of applications. PMID- 17271623 TI - Framework for developing a hierarchical model of reward focusing on the nucleus accumbens. AB - Computational modeling using GENESIS platform has led to advances in fabricating a model to test the influence of molecular/proteomic adaptations on behavior due to reward. The nucleus accumbens is an area of the brain that processes information from other parts of the brain and is an integral element of the 'reward pathway' in the brain. A simplified model of the accumbens using one neuron is developed as part of a larger effort to study reward and chemical dependency with a focus on cocaine addiction. A preliminary model of a biologically realistic neuron was developed with inhibitory and excitatory afferents as well as intrasynapse dynamics. The neuron displayed characteristic behavior of a neuron found in the nucleus accumbens including bistability. The neuron has afferents from other neurons via dendrites which carry the inputs relating to behavioral aspects and to learning. To add behavioral aspects to the model, a methodology is developed to model contexts and their reinforcing effects on behavior, similar to cocaine addiction. Results using both the biological and behavioral modeling are encouraging for this preliminary model. PMID- 17271624 TI - Multiplexed electrochemical protein coding based on quantum dot (QD) bioconjugates for a clinical barcode system. AB - An ultrasensitive imumunodiagnostic readout method based on an electrochemical analysis is presented. Different high-quality quantum dot (QD) nanocrystals (ZnS, CdS, and PbS) are tagged to antibodies for the on-site voltammetric stripping measurements of multiple antigen targets. These encoding QD tracers with distinct redox potential yield highly sensitive and selective stripping peaks at -1.11 V (Zn), -0.67 V (Cd) and - 0.52 V (Pb) at the mercury-coated glassy carbon electrode (vs. Ag/AgCI reference). The position and size of these peaks reflect the identity and level of the corresponding antigen target. The analog peaks of the QDs were converted to a digital bio-barcode system for simple and rapid medical diagnostics. PMID- 17271626 TI - Impulse rejection filter for artifact removal in spectral analysis of biomedical signals. AB - Biomedical signals are frequently corrupted with artifact that occurs rarely, but is impulsive and large amplitude when it does occur. Because the artifact spans a broad frequency range that overlaps with the signal spectrum, linear filters cannot remove it. Because it is large in amplitude, it dominates characterizations of the signals based on second-order statistics such as correlation and spectral analysis. In this study we assess the ability of impulse rejection filters to remove the effect of synthetic PVCs in interbeat interval series from patients with a normal sinus rhythm. The simulation results demonstrate that the PVCs severely corrupt the estimated heart rate power spectral density (PSD), impulse rejection filters are effective at removing this effect, and the filter performance is robust to the choice of user-specified parameters. PMID- 17271625 TI - Spectral analysis for diagnosis of esophagus dysplasia using fluorescence Raman spectroscopy. AB - In this paper, we present a three parametric model using Raman and fluorescence spectroscopy for detection and analysis of esophagus dysphasia and esophagus cancer. The model was set up from more than 200 samples. And 40 samples were used to test this algorithm of the model prospectively. The serum spectra were excited by laser of the wavelength 488.0 nm and 514.5 nm. The apparent differences of auto-fluorescence and Raman spectroscopy were observed for patients compared to the normal: the majority of the fluorescence spectra did not have violent alteration, but three Raman peaks had disappeared or very weak. For successful operation, the Raman spectrum of patient's serum is similar to the normal. Moreover, Delta lambda value(red shift of fluorescence peak) and alpha-value (rate of fluorescence intensity) also provide the reference for future research. And beta-value(rate of Raman peak intensity) will decrease with progression of the tumor. The result of spectrum analysis is accordance with the clinical diagnosis. PMID- 17271627 TI - Adaptation of multi-joint movements during postural disturbances. AB - The objective was to investigate the adaptation of the multi-segmented body movements induced over time by vibratory proprioceptive stimulation of the calf muscles and by galvanic vestibular stimulation. Twelve normal subjects were with eyes open or eyes closed exposed to vibratory stimulation of two different amplitudes and frequencies, or to simultaneously applied galvanic and vibratory stimulation. Multi-input multi-output system identification methods as well as quantitative analysis were applied to the biomechanical experimental data of anteroposterior and lateral body movements and torques induced towards the ground. The immediate adaptive response to the stimulation onset was that the subjects adopted a more rigid posture with coordinated movements of primarily head-shoulder and head-hip body segments. The body-movement amplitudes at all measured sites as well as the amplitudes of the ground support forces decreased over time as a result of another, somewhat slower adaptation process. The subjects required more time to adapt to a rigid movement pattern when the subjects were simultaneously exposed to both galvanic and vibratory stimulation. Moreover, the accuracy of the MIMO model and correlation analysis between measured torque variance and head; shoulder; hip and knee movement variance suggests that force platform recordings reflect both in anteroposterior and lateral direction the body movements at these sites. PMID- 17271628 TI - Analysis for fMRI feature of anxiety disorder patient by language stimulation. AB - The related studies have show that anxious disorder (AD) is associated with two factors: psychogenic and organic origin. In this study, using the functional magnetic resonance imaging (fMRI), we detect the responses in interrelated brain regions to different categories of auditory stimulation. The mathematic modeling was modeled according to the response data acquired, in order to study the correlative quantificational feature between the psychogenic stimulus and organic response. Then, the study tries to get a way to predict AD. In the further study, this research is helpful to study the pathogenesis of AD, diagnose AD in clinic and estimate the curative effect. PMID- 17271629 TI - Power spectral density estimation and tracking nonstationary pressure signals based on Kalman filtering. AB - We describe an algorithm to estimate and track slow changes in power spectral density (PSD) of nonstationary pressure signals. The algorithm is based on a Kalman filter that adaptively generates an estimate of the autoregressive model parameters at each time instant. The algorithm exhibits superior PSD tracking performance in nonstationary pressure signals than classical nonparametric methodologies, and does not assume a piecewise stationary model of the data. Furthermore, it provides better time-frequency resolution, and is robust to model mismatches. We demonstrate its usefulness by a sample application involving PSD estimation and tracking of short records of simulated pressure waveforms. This algorithm is intended for applications were the PSD must be estimated and tracked during short transient periods, possibly after clinical interventions. PMID- 17271630 TI - Code excited linear prediction codec for electrocardiogram. AB - In this paper we propose a CELP ECG codec for medical telemetry. The encoding algorithm is based on CODE-EXCITED LINEAR PREDICTION (CELP). The general framework proposed is: QRS detection, calculation of LPC parameter, generation of residual error signal, codebook generation, MSE (mean square error) search. The codebook is generated for residual error. The indices of the codebook and corresponding LPC parameters are transmitted where the minimum MSE occurs. A replica of the transmitter codebook is present at the receiver. Corresponding to the received index value residual error coefficients are retrieved from the receiver codebook. The ECG signal is reconstructed from the retrieved code word. PMID- 17271631 TI - Entropy based method to correct intensity inhomogeneity in MR images. AB - We are involved in a comprehensive program to characterize atherosclerotic disease using multiple MR images having different contrast mechanisms (T1W, T2W, PDW, magnetization transfer, etc.) of human carotid and animal model arteries. We use specially designed intravascular and surface array coils that give high signal-to-noise but suffer from sensitivity inhomogeneity and significant noise. We present here a new non-parametric method for correcting the images without assumption of the number of different tissues. Intensity inhomogeneity is modeled with cubic spline and is locally optimized using an entropy criterion. Validation has been performed on a specially design neck phantom as well as actual MR scans on patient neck. The steep bias is corrected sufficiently to aid human interpretation of gray scales. It should also make possible computerized tissue classification. PMID- 17271632 TI - Measurement of color discrimination threshold using visually evoked potential and its correlation with psychophysical measure. AB - Purpose was to determine whether our developed electrophysiological technique (Momose and Saito, 2002) using visually evoked potential (VEP) is effective for determining the color discrimination threshold in human. Both VEP and psychophysical color matching measurement were applied to three normal volunteers, and their correlation and sensitivity were investigated. Colors on the MacAdam ellipse were selected for stimulus. Threshold determined by VEP was well correlated with psychophysical measure (r = 0.88 and 0.75 in two subjects), and was about 24 times higher than psychophysical ones. VEP measurement was done within much shorter time (30 min.) than psychophysical method (3 hours). VEP determined color discrimination threshold can be effective for the human color vision testing. PMID- 17271633 TI - Consolidating software tools for DNA microarray design and manufacturing. AB - As the human genome project progresses and some microbial and eukaryotic genomes are recognized, a novel technology, DNA microarray (also called gene chip, biochip, gene microarray, and DNA chip) technology, has attracted increasing number of biologists, bioengineers and computer scientists recently. This technology promises to monitor the whole genome at once, so that researchers can study the whole genome on the global level and have a better picture of the expressions among millions of genes simultaneously. Today, it is widely used in many fields - disease diagnosis, gene classification, gene regulatory network, and drug discovery. We present a concatenated software solution for the entire DNA array flow exploring all steps of a consolidated software tool. The proposed software tool has been tested on Herpes B virus as well as simulated data. Our experiments show that the genomic data follow the pattern predicted by simulated data although the number of border conflicts (quality of the DNA array design) is several times smaller than for simulated data. We also report a trade-off between the number of border conflicts and the running time for several proposed algorithmic techniques employed in the physical design of DNA arrays. PMID- 17271634 TI - Brain dynamical disentrainment by anti-epileptic drugs in rat and human status epilepticus. AB - In this paper, we utilize a measure of brain dynamics, namely the short-term largest Lyapunov exponent (STLmax) to evaluate the efficacy of treatment in epileptic animals and humans with known antiepileptic drugs (AED) like diazepam and phenobarbital during status epilepticus (SE). This measure is estimated from analysis of electroencephalographic (EEG) recordings at multiple brain locations in both an SE patient and a cobalt/homocysteine thiolactone SE-induced animal. Techniques from optimization theory and statistics are applied to select optimal sets of brain sites, whose dynamics are then measured over time to study their entrainment/disentrainment. Results from such analysis indicate that the observed abnormal spatio-temporal dynamical entrainment in SE is reversed by AED administration (resetting of brain dynamics). These results may provide a potential use of nonlinear dynamical measures in the evaluation of the efficacy of AEDs and the development of new treatment strategies in epilepsy. PMID- 17271635 TI - Compression of long-term EEG using power spectral density. AB - In this paper, we propose to use the features based on power spectral density as a descriptor of the EEG in the compression of the long-term intensive care unit EEG to obtain the temporal evolution of the recurrent patterns. Sleep EEG is used as a baseline since the sleep stages can be mapped to recurrent patterns in the background EEG. Our results indicate that the spectral features provide a better classification of the sleep EEG and assist in a better formation of homogenous clusters compared to the results obtained with the previously used features. The average overall agreement compared against manual scoring of seven sleep EEG records is 68.5%. It is an improvement compared to 62.7% obtained with the previously used features. Although our results for computer classification use only the EEG information from one frontal and one occipital channel, they are similar to the manual classification of sleep EEG, which is based on additional information. PMID- 17271636 TI - Optimised attribute selection for emotion classification using physiological signals. AB - Researchers in medicine and psychology have studied emotions and the way they influence human thinking and behaviour for decades. Recently computer scientists have realised the importance of emotions in human interactions with the environment and a considerable amount of research has been directed towards the identification and utilisation of affective information. Particular interest exists in the detection of emotional states with the intention of improving both human-machine interaction and artificial human-like inference models. Emotion detection has also been employed to explore applications that relate emotional states, habits and ambient conditions inside inhabited environments. Valuable information can be obtained by analysing the way affective states that influence behaviour are altered by environmental changes. In this paper an analysis of the properties of four physiological signals employed in emotion recognition is presented. Class separation analysis was used for determining the best physiological parameters (among those from a list chosen a priori) to use for recognizing emotional states. Results showed that the masseter electromyogram was the best attribute when distinguishing between neutral and non-neutral emotional states. Using Autoassociative Neural Networks for improving cluster separation, the gradient of the skin conductance provided the best results when discriminating between positive and negative emotions. PMID- 17271637 TI - Multi-class cancer classification by semi-supervised ellipsoid ARTMAP with gene expression data. AB - To accurately identify the site of origin of a tumor is crucial to cancer diagnosis and treatment. With the emergence of DNA microarray technologies, constructing gene expression profiles for different cancer types has already become a promising means for cancer classification. In addition to binary classification, the discrimination of multiple tumor types is also important semi supervised ellipsoid ARTMAP (ssEAM) is a novel neural network architecture rooted in adaptive resonance theory suitable for classification tasks. ssEAM can achieve fast, stable and finite learning and create hyper-ellipsoidal clusters inducing complex nonlinear decision boundaries. Here, we demonstrate the capability of ssEAM to discriminate multi-class cancer through analyzing two publicly available cancer datasets based on their gene expression profiles. PMID- 17271639 TI - An unsupervised classification method of uterine electromyography signals using wavelet decomposition. AB - The purpose of this study is to classify the uterine contractions in the electromyography (EMG) signal. As the frequency content of the contraction changes from one woman to another and during the pregnancy, wavelet decomposition is used to extract the parameters of each contraction, and an unsupervised statistical classification method based on Fisher test is used to classify events. A principal component analysis projection is then used to evidence the groups resulting from this classification. Results show that uterine contractions may be classified into independent groups according to their frequency content. PMID- 17271641 TI - EEG feature extraction for classification of sleep stages. AB - Automated sleep staging based on EEG signal analysis provides an important quantitative tool to assist neurologists and sleep specialists in the diagnosis and monitoring of sleep disorders as well as evaluation of treatment efficacy. A complete visual inspection of the EEG recordings acquired during nocturnal polysomnography is time consuming, expensive, and often subjective. Therefore, feature extraction is implemented as an essential preprocessing step to achieve significant data reduction and to determine informative measures for automatic sleep staging. However, the analysis of the EEG signal and extraction of sensitive measures from it has been a challenging task due to the complexity and variability of this signal. We present three different schemes to extract features from the EEG signal: relative spectral band energy, harmonic parameters, and Itakura distance. Spectral estimation is performed by using autoregressive (AR) modeling. We then compare the performance of these schemes with the view to select an optimal set of features for specific, sensitive, and accurate neuro fuzzy classification of sleep stages. PMID- 17271643 TI - Simulation and extraction of single-trial evoked potentials. AB - Evoked potentials are defined as potentials that result from electrical activity in the central nervous system after a stimulation. In analysis of evoked potentials the main problem is to extract the waveform from measurements that also contain on-going background electroencephalographic (EEG) activity. The conventional tool for the analysis of evoked potentials has been averaging of the measurements over an ensemble of trials. This is the optimal way to improve the signal-to-noise ratio when the evoked potential is a deterministic signal in independent and additive background noise of zero mean. However, it is evident that the evoked potential varies with repetitions of the stimuli. There are two aims of this paper. The first is to develop a simulation method for evoked potentials with slow variations among different trials. The second aim is to develop a method to extract time variations occurring in a number of time-aligned trials to estimate the single-trial evoked potentials. PMID- 17271645 TI - Detection of oxidized low density lipoproteins by indium oxide nanowires-based field effect transistor. AB - Oxidized low density lipoprotein (oxLDL) particles are known to initiate the development of coronary artery disease. Field effect transistors (FET) made of indium oxide (In2O3) nanowires have been demonstrated as sensitive chemical sensors for gaseous molecules such as NO2 and NH3. We hereby, apply In2O3 nanowires FETs to differentiate oxLDL from native LDL (nLDL), cytochrome-c and bovine serum albumin in terms of the transistor characteristic curves: I(D)-V(GS) (current versus drain-source voltage) and I(D)-V(GS) (current versus gate-source voltage). Measurements under static and flow conditions revealed that exposure of nanowires to these redox proteins selectively changed the FET conductivity and the gating effect of the transistors. To enhance the selectivity for oxLDL detection, surface chemistry modification with antioxLDL antibody was performed. PMID- 17271646 TI - Statistical modeling of biochemical detection systems. AB - We study the problem of counting the number of particles in a closed volume where the particles motion are modeled by a Brownian motion process. This problem arises in many biological and chemical sensing experiments, e.g., counting the number of analytes in blood sample, air pollutant measurement, etc. Finding the exact count of particles is challenging in these systems and one generally relies on an estimate based on the sample readouts. We study the statistical properties of the counting process in equilibrium and present the fundamental detection and estimation limitations. In particular, we demonstrate that the count process is inherently noisy and has a quantum-limit signal to noise ratio. PMID- 17271647 TI - Raman spectroscopy and fluorescence for the detection of liver cancer and abnormal liver tissue. AB - In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra in serum differences between normal people and liver cancer patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5 nm is higher than that excited by 488.0 nm. However, for the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The results from more than two hundred case measurements show that the spectral diagnosis was in good agreement with the clinical result. Moreover, the liver fibrosis and liver cirrhosis were studied using the technology of LIF. The experiment indicates that the blue shift of fluorescence peak difference between the normal, liver fibrosis and liver cirrhosis were observed. These results have important reference values to explore the method of laser spectrum diagnosis. PMID- 17271648 TI - Determination of the systematic and random measurement error in an LC-FTICR mass spectrometry analysis of a partially characterized complex peptide mixture. AB - In high-throughput proteomics, a promising approach presently being explored is the use of liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS) to provide measurements of the masses of tryptic peptides in complex mixtures, which can then be used to identify the proteins which gave rise to those peptides. In order to apply this method, it is necessary to account for any systematic measurement error, and it is useful to have an estimate of the random error in measured masses. In this investigation, a complex mixture of peptides derived from a partially characterized sample was analyzed by LC-FTICR-MS. Through the application of a Bayesian probability model of the data, partial knowledge of the composition of the sample is sufficient both to determine any systematic error and to estimate the random error in measured masses. PMID- 17271649 TI - Surface analysis of peptide mass spectra to improve time and mass localization. AB - Current peak detections algorithms for processing mass spectrometry (MS) spectra generally rely on two dimensional techniques for identifying the location and intensity of peaks from a single spectrum. However, when high performance liquid chromatography (HPLC) is coupled with mass spectrometry, a third dimension, retention time, is introduced. The ensemble of MS spectra may then be regarded as a 3D surface where spectral intensity is a function of m/z (mass-to-charge) and time. This suggests that peak localization can be improved by incorporating the time domain data and average data across both dimensions. This work describes a surface intensity analysis algorithm and the results of its use. PMID- 17271650 TI - Development of a new signal processing algorithm based on independent component analysis for single channel ECG data. AB - In this paper, we proposed a new signal processing algorithm based on independent component analysis (ICA) for single channel ECG data. For the application ICA to single channel data, mixed (multi-channel) signals are constructed by adding some delay to original data. By ICA, signal enhancement is acquired. For validation of usefulness of this signal, QRS complex detection was accompanied. In QRS detection process, Hilbert transform and wavelet transform were used and good QRS detection efficacy was obtained. Furthermore, a signal, which could not be filtered properly using existing algorithm, also had better signal enhancement. In future, we need to study on the algorithm optimization and simplification. PMID- 17271651 TI - Principal component analysis and interpretation of bowel sounds. AB - This paper presents a method for abdominal sounds analysis based on principal component analysis (PCA). The first steps (wavelet denoising and segmentation, followed by spatial localization) were presented in previous works. After extracting physical features (activity indices) from long time six channel recordings, we propose a reduced representation space obtained by PCA and we present our results in phonoenterogram analysis. PMID- 17271652 TI - Independent component analysis of pulse oximetry signals. AB - This paper describes the application of Independent Component Analysis (ICA) to signals from a pulse oximeter, an instrument that measures arterial blood oxygen content. ICA uses estimates of the second- and higher-order joint statistics of the input signals to separate the signal and interference. For time-derivative pulse oximetry signals, the skew of the arterial pulse component is generally much greater than that of the interference, and this can be used to aid the separation. This paper shows an example of ICA used on pulse oximetry signals and then presents simulations to demonstrate that, for pulse oximetry signals, ICA based on third-order statistics of the derivative is indeed superior to fourth order ICA. PMID- 17271653 TI - ICA-based classification scheme for EEG-based brain-computer interface: the role of mental practice and concentration skills. AB - This article explores the use of independent component analysis (ICA) approach to design a new EEG-based brain-computer interface (BCI) for natural control of prosthetic hand grasp. ICA is a useful technique that allows blind separation of sources, linearly mixed, assuming only the statistical independence of these sources. This suggests the possibility of using ICA to separate different independent brain activities during motor imagery into separate components. This work provides a natural basis for developing an efficient BCI based on single source data obtained by independent component analysis of multi-channel EEG. The tasks to be discriminated are the imagination of hand grasping and opening and the resting state. The results indicate that the proposed scheme can improve the classification accuracy of the EEG patterns. Imagery is the essential part of the most EEG-based communication systems. Thus, the quality of mental rehearsal, the degree of imagined effort, and mind controllability should have a major effect on the performance of EEG-based BCI. We are going to examine the role of mental practice and concentration skills on the performance of BCI. The surprising results indicate that mental training has a significant effect on the performance of BCI over the primary motor cortex, temporal, and frontal areas. This supports the hypothesis that mental practice is an effective method for performance enhancement and motor skill learning. PMID- 17271654 TI - The effects of mental practice and concentration skills on EEG brain dynamics during motor imagery using independent component analysis. AB - It is now well established that mental practice using motor imagery improves motor skills. The effects of mental practice on motor skill learning are the result of practice on central motor programming. According to this view, it seems logical that mental practice should modify the neuronal activity in the primary sensorimotor areas. This article explores the use of independent component analysis (ICA) approach to characterize the effect of mental practice and concentration skills on EEG patterns during motor imagery. The results indicate that the mental training has a significant effect on spatial-temporal EEG during motor imagery. It is observed that the power of delta and theta bands increases following the visual cue and alpha activity is significantly suppressed. Increase of gamma activities starts almost 1000 ms after the visual stimulus and continues to the end of imagination. Increase of theta activities can be associated with engagement of the working memory during motor imagery and represents the memory load. The interesting result is that the mental training dramatically enhances motor-cortex rhythm. It is found that ICA can successfully detect and separate different brain activities into separate components during motor imagery. PMID- 17271655 TI - Electrocardiogram removal from electromyogram of the muscles. AB - Surface electromyogram (SEMG) of the lumbar back muscles is being used for determining posture disorders for people suffering from low back pain. But SEMG of the back has a strong electrocardiogram (ECG) artefact. Research was conducted to determine the difference in the SEMG before and after the removal of ECG artefact from the SEMG recording using gating, subtraction and multi-step independent component analysis (MICA). The paper reports results of experiments conducted on eleven subjects over two days. The results show that removal of ECG artefact from the raw signal can substantially alter the RMS of the signal demonstrating the need for careful filtering of the signal for analysis. The paper also reports of the success of MICA for removing the ECG artefact. PMID- 17271656 TI - Comparing methods to denoise mammographic images. AB - Digital mammographic image processing often requires a previous application of filters to reduce the noise level of the image while preserving important details. This may improve the quality of digital mammographic images and contribute to an accurate diagnosis. In the literature, one can find a large amount of denoising techniques available for different kinds of images. We have adapted some of the existing denoising algorithms to mammographic images. We compare the effect of different denoising filters acting on digitized mammograms. The considered filters are: a local Wiener filter, a wavelet filter, a filter based on independent component analysis, and finally, a filter based on the diffusion equation. The noise reduction is measured by the mean squared error. PMID- 17271657 TI - Multiresolution analysis for early diagnosis of Alzheimer's disease. AB - Early diagnosis of Alzheimer's disease is a major concern due to large portions of the elderly population it affects and the lack of a standard and effective diagnosis procedure that is available to community healthcare providers. Several studies have been performed using wavelets or other signal processing methods to analyze EEG signals in an attempt to find a biomarker for Alzheimer's disease, which showed varying degrees of success. To date, in part due to lack of a large study cohort, the results of these studies remain largely inconclusive. In this paper, we describe a new effort using multiresolution wavelet analysis on event related potentials of the EEG to investigate whether such a link can be established. Several factors sets this study apart from similar prior efforts: We use a larger cohort, compare different mother wavelets, rather then using one generic wavelet, and most importantly, we specifically target early diagnosis of the disease. Our multi-year effort will include a total of 80 patients, whose ERPs will be analyzed with several different wavelets and automated classifiers. We present some preliminary, yet very promising, results on analysis of EEGs of the first 28 patients analyzed thus far using two types of wavelets. PMID- 17271659 TI - A study on binocular rivalry based on the steady state VEP. AB - Under conditions in which the visual system can not reconcile dissimilar images from the two eyes, perception typically alternates between the two images - a process known as binocular rivalry. This work presents a method based on the time frequency analysis of the steady-state visual evoked potentials (SSVEP) that continuously registers the alternation in physiological dominance of the two eyes. Two images flickered at different frequencies as the visual stimulator to left and right eyes respectively so that the response can be recovered from the EEG by time-frequency analysis. The physiological dominance of each eye as evidenced by the SSVEP record correlates well with the subjects' report of perceptual dominance. This electrophysiological method appears to be suitable for measuring rivalry in non-verbal human or animals. PMID- 17271658 TI - A wavelet based analysis of energy redistribution in scalp EEG during epileptic seizures. AB - In this work, wavelet decomposition and multiresolution analysis are used to explore the changes in scalp EEG signals during epileptic seizures. EEG tracings, which include non-epileptic periods, the beginning of seizure and the peak of seizure, have been decomposed in five details using order 10 Daubechies orthonormal wavelets. Energy has then been computed, at each detail, from square wavelet coefficients, in order to unmask the presence of brief episodes of energy relocation among different scales. Results reveal the existence of significant changes in energy distribution at seizure onset; this redistribution, however, exhibits significant differences from one patient to another, and also among different channels in the same patient. Some channels exhibit a significant energy increase at low scales (high frequencies greater than 20 Hz) at seizure onset, whereas energy drops at higher scales. Other channels, however, exhibit energy increase at high scales (frequency less than 15 Hz) revealing a predominance of low-frequency activity. These two patterns may be simultaneously present at seizure onset and may change with different spatial evolution during the subsequent seizure progression. Wavelet analysis appears as a powerful tool for extracting features relative to seizure, and to study their propagation among different regions in the scalp. PMID- 17271660 TI - Comparison of two estimators of time-frequency interdependencies between nonstationary signals: application to epileptic EEG. AB - Numerous works have been dedicated to the development of signal processing methods aimed at measuring the degree of association between EEG signals. This interdependency parameter is often used to characterize the functional coupling between different brain structures or regions during either normal or pathological processes. In this paper we focus on the time-frequency characterization of interdependencies between nonstationary signals. Particularly, we propose a novel estimator based on the cross correlation of narrow band filtered signals. In a simulation framework, results show that this estimator may exhibit higher statistical performances (bias and variance) compared to a more classical estimator based on the coherence function. On real data (intracerebral EEG signals), they show that this estimator enhances the readability of the time-frequency representation of the relationship and can thus improve the interpretation of nonstationary interdependencies in EEG signals. Finally, we illustrate the importance of characterizing the relationship in both time and frequency domains by comparing with frequency-independent methods (linear and nonlinear). PMID- 17271661 TI - Time-frequency analysis of visual evoked potentials by means of matching pursuit with chirplet atoms. AB - Detection of visual evoked potentials (VEP) elicited by repetitive stimuli is valuable in both laboratorial research and clinical practice. Therefore, knowing the characteristics of VEPs is of fundamental importance for adequate design of a signal detector. Usually, the signal is modeled as a steady-state VEP (ssVEP) consisting of the fundamental frequency and the higher harmonics, while ignoring the information contained in its transients (tVEP). We propose here to characterize both tVEP and ssVEP by chirplet time-frequency representation of VEP signal using a matching pursuit (MP) algorithm. Compared to the time-frequency analysis with short-time-Fourier-transform (STFT) and linear-prediction-coding (LPC) method, MP with chirplet shows not only clear characteristics of ssVEP, but a clear spindle-like time-frequency component of tVEP as well, which is not obvious in the other two methods. PMID- 17271662 TI - Lomb-Wech periodogram for non-uniform sampling. AB - The Lomb-Scargle transform has been proposed for the direct evaluation, namely without interpolation, of non-uniformly sampled signals. In its current form, it is suitable only for single transform evaluation due to the implicit normalization. Enhancements of this transform are proposed to allow the evaluation of shorter transforms, combined with windows and averaging of overlapped records. This requires a de-normalization of the transform by a factor of 2(sigma)/sup 2//N, the use of equal time duration records, and multiplication by windows sampled at corresponding non-uniform time instances. This results in a Welch-like periodogram for non-uniform sampling. PMID- 17271663 TI - Feature extraction of the atrial fibrillation signal using the continuous wavelet transform. AB - Despite advances in cardiac arrhythmia management, atrial fibrillation remains a major cause of cardiovascular morbidity and mortality. Recent data suggests that there are periods of organization within this apparently chaotic arrhythmia. To date, analysis of the rapidly changing atrial fibrillation signal has been limited by a lack of time-frequency resolution. When used to analyze high-density atrial mappings of this arrhythmia, the continuous wavelet transform, with its time-frequency multi-resolution capability, may provide important temporal and spatial information regarding arrhythmia organization and may lead to the development of more effective therapies. PMID- 17271664 TI - An improvement of unsupervised hybrid biomedical signal classifiers by optimal feature extraction in system preliminary layer. AB - In this paper we try to place emphasis especially on the feature extraction stage of classification procedure, where new feature vectors obtained from a high dimensional data space, which the best match the analysed classification task are proposed. Based on multilevel Mallat wavelet decomposition, parameters obtained directly from the wavelet component as well as feature resulting from energy and entropy analysis are tested. In classifier part of proposed hybrid systems, unsupervised learning systems with self organizing maps (SOM) and adaptive resonance networks (ART2) are verified. T-F methods and particularly wavelet analysis was chosen as feature extraction tool because of its ability to deal with non-stationary signals. It is important to take into consideration, that heart rate variability (HRV) signals, which were classified in elaborated systems are nonstationary and have important parameters included both in time and frequency domain. Proposed structures were tested using the set of clinically characterized heart rate variability (HRV) signals of 62 patients, as cases with a coronary artery disease of different level. Additionally similar control group of healthy patients was analyzed. Whole database was divided into learning and verifying set. Results showed, that the new HRV signal representation obtained in the space created by the feature vector based on Shannon entropy of Mallat component energy distribution gave the best classifier performance with ART2 neural structure used in classifier part of described hybrid system. PMID- 17271665 TI - The analysis of mental stress using time-frequency distribution of heart rate variability signal. AB - Conventional power spectrum methods based on fast Fourier transform (FFT), autoregressive(AR) model are not appropriate for analyzing biomedical signals whose spectral characteristics change rapidly. On the other hand, time-frequency analysis has more desirable characteristics of a time-varying spectrum. In this study, we investigated the spectral components of heart rate variability (HRV) in a time-frequency domain. Then, from the instantaneous frequency, obtained from time-frequency distribution, the method extracting frequency components of HRV was proposed. The subjects were 17 healthy young men. A coin-stacking task was used to induce mental stress. In the results, the emotional stress of subjects produced an increase in sympathetic activity. Sympathetic activation was responsible for the significant increase in the LF/HF ratio. The subjects were divided into two groups with task ability. The subject who had higher mental stress had a lack of task ability. PMID- 17271666 TI - Non stationary analysis of heart rate variability during the obstructive sleep apnea. AB - Characteristic fluctuations of the heart rate are found during obstructive sleep apnea (OSA), bradycardia in apneonic phase and tachycardia at the recovery of ventilation. In order to assess its autonomic response, in this study, the time frequency distribution of Born-Jordan and evolutive Poincare plots are used. From Physionet was taken a database with records of ECG and respiratory signals. During the OSA all spectral indexes presented oscillations correspondent to the changes between brady and tachycardia of the RR intervals as well as greater values than during control epochs. Born-Jordan distribution and evolutive Poincare plots could help to characterize and develop an index for the evaluation of OSA. Very low frequency could also be a good index of OSA. PMID- 17271667 TI - Time-frequency analysis of the ECG in the diagnosis of vasovagal syndrome in older people. AB - The Smoothed Pseudo Wigner-Ville Distribution (SPWVD) is used for the time frequency analysis of variations in RR interval. A novel technique to determine the smoothing window lengths is implemented, and a new heart rate variability (HRV) metric is developed, instantaneous center frequency variability (ICFV), which uses the time-frequency map generated by the SPWVD. The technique is then applied to 50 patients with unexplained falls and age > 60, undergoing head upright tilt table testing (HUT). Eighteen of the patients were diagnosed with vasovagal syndrome. Attempts at syncope prediction using the new metric is an improvement on traditional techniques: an ICFV less than 0.07 Hz from 90 s to 180 s after tilt is predictive of a negative test (negative predictive value: 0.77). The comorbidity and autonomic degeneration present in elderly patients are thought to be responsible for lowering the negative predictive value. PMID- 17271668 TI - Heart rate variability analysis of effect of nicotine using periodograms. AB - Heart rate variability (HRV) is frequently used to measure autonomic nervous system (ANS) activity. However, little is known about the mechanism underlying pharmacologically induced changes in HRV. Previous research has shown that nicotine exposure stimulates the ANS, mediating a wide spectrum of physiological and behavioral effects, including altered respiratory sinus arrhythmia and enhanced arousal and attention. Using Lomb-Welch periodograms, the effect of nicotine on the ANS in 14 nicotine-naive human subjects are studied. Results showed an increase in the low frequency (LF) to high frequency (HF) ratio with little change in mean heart rate. Results suggest that nicotine affects both sympathetic and parasympathetic reactivities and that the LF/HF best characterizes early ANS activated nicotine changes in HRV. The Lomb-Welch periodogram of the HRV is also compared to the conventional interpolated Welch periodogram. The attenuation of the high frequency components due to interpolation of the non-uniform R-R intervals is found to be a function of the power of the high frequency components, increasing with increasing power. Thus analyses using Welch periodograms that make use of the high frequency components may yield erroneous results. PMID- 17271669 TI - Estimation of time-varying coherence function using time-varying transfer functions. AB - We introduce a new method to estimate reliable time-varying coherence functions (TVCF). The technique is based on our previously developed method to estimate time-varying transfer functions (TVTF), known as the time-varying optimal parameter search algorithm (TVOPS) [1]. The TVCF is estimated by the multiplication of the two TVTFs. The two TVTFs are obtained using signal x as the input and signal y as the output to produce the first TVTF, and signal y as the input and signal x as the output to produce the second TVTF. Demonstration of the feasibility and efficacy of the proposed approach is provided with both simulation examples and application to renal blood flow and pressure data. The proposed approach provides higher time-frequency resolution TVCF than afforded by the short time Fourier transform based TVCF. PMID- 17271670 TI - Analysis and visualization of ERD and ERS with Adapted Local Cosine Transform. AB - We apply Adapted Local Cosine Transform to movement EEG, which is a local spectral representation of the signal. It includes best basis method obtained by entropy minimization. The algorithm yields to adaptive time segmentation, where these segments correspond to ERD and ERS events. The algorithm provides short segments in ERD and ERD to ERS transitions. Then we use averaged DCT coefficients to extract the ERD ERS structure of a person. PMID- 17271671 TI - On evaluation of spectrum estimators for EEG. AB - In the search for how neonatal EEG is affected by asphyxia it is of importance to find reliable estimates of EEG power spectra. Several spectral estimation methods do exist, but since the true spectra are unknown it is hard to tell how well the estimators perform. Therefore a model to generate simulated EEG with known spectrum is proposed and the model is used to evaluate performance of several parametric and Fourier based spectral estimators. PMID- 17271672 TI - Gabor atom density as a measure of seizure complexity. AB - The Gabor atom density (GAD) is a measure of complexity of a signal. It is based on the time-frequency decomposition obtained by the matching pursuit (MP) algorithm. The GAD/MP method was applied to EEG data recorded from intracranial electrodes in patients with intractable complex partial seizures. GAD shows that epileptic seizures, which are reflections of increased neuronal synchrony, are also periods of increased and changing signal complexity. The GAD/MP method is well suited to analyzing these signals from seizures characterized by rapid dynamical changes. The period of organized rhythmic activity exhibits lower complexity than that seen during other phases of the seizure. PMID- 17271673 TI - Acoustic analysis of the infant cry: classical and new methods. AB - In the last few decades many papers have written about the analysis of the infant cry. The acoustic analysis has a shorter history than emotional, physiological, etc. investigations [1, 2, 3, 4, 5]. This paper deals with classical and new methods of acoustic analysis of the infant cry. The final goal is to detect hearing disorders according to the crying at the earliest possible moment. Classical acoustic methods were reproduced and compared with solutions, which were not available before. This paper most of all deals with the characteristics of the fundamental frequency of the cry in the time and in the frequency domain. PMID- 17271674 TI - Monitoring respiratory rate based on tracheal sounds. First experiences. AB - The objective was to develop a non-invasive method for continuously monitoring respiratory rate (RR) based on tracheal sounds. 25 volunteers and 36 patients with chronic pulmonary diseases were enrolled in a clinical study. Tracheal sounds were acquired using a contact piezoelectric sensor placed on the examinee's throat and analyzed using a combined investigation of the sound envelope and frequency content. RR estimates were compared to reference measurements taken from a pneumotachometer coupled to a face mask worn by the examinee. RR was also manually counted by a respiratory technician. Two types of breathing (mouth and nose) and three different positions were studied (fowler, semi-fowler and supine). RR estimated in volunteers had a success rate (SR) of 96%, a correlation coefficient (r) of 0.99 and a standard error of the estimate (SEE) of 0.56. The RR estimated in patients was comparable or slightly better (SR = 85%, r = 0.93 and SEE = 1.49) than those obtained by manual count (SR = 82%, r = 0.91, SEE = 1.58), which is the method widely used in clinical settings. No significant difference in the capacity to estimate RR was found related to posture and breathing type, making this method useful for continuous monitoring. PMID- 17271675 TI - Automated detection of obstructive apnea and hypopnea events from oxygen saturation signal. AB - Our objective is to automate the detection of apnea and hypopnea events in obstructive sleep apnea hypopnea (OSAH) syndrome based on analysis of arterial oxygen saturation signal alone. This is the first attempt where wavelet is used to detect OSAH events. Detection of OSAH events through wavelet depends on the fluctuations in the magnitude of the transformed coefficients, thus circumventing the problem of variability in the criteria on the magnitude and duration of the signal. Our work evaluates the performance of the wavelet transform to detect OSAH events against three conventional amplitude and duration algorithms. High performance in the detection of OSAH events can be achieved through the wavelet algorithm (score 96.55%, sensitivity 95.74% and specificity 97.02%) if the threshold on wavelet coefficients is individually tuned for each study. However, this is impossible in clinical practice. It is interesting to observe that the conventional methods based on amplitude and duration are able to attain a performance as close as this. The Nervus algorithm obtains the best result (score 96.66%, sensitivity 95.26% and specificity 97.46%) compared to the amplitude duration algorithm, the drop duration algorithm and the wavelet algorithm with global threshold, in descending order of performance. PMID- 17271676 TI - Using a forehead reflectance pulse oximeter to detect changes in sympathetic tone. AB - The extreme conditions of combat and multi-casualty rescue often make field triage difficult and put the medic or first responder at risk. In an effort to improve field triage, we have developed an automated remote triage system called ARTEMIS (automated remote triage and emergency management information system) for use in the battlefield or disaster zone. Common to field injuries is a sudden change in arterial pressure resulting from massive blood loss or shock. In effort to stabilize the arterial pressure, the sympathetic system is strongly activated and sympathetic tone is increased. This preliminary research seeks to empirically demonstrate that a forehead reflectance pulse oximeter is a viable sensor for detecting sudden changes in sympathetic tone. We performed the classic supine standing experiment and collected the raw waveform, the photoplethysmogram (PPG), continuously using a forehead reflectance pulse oximeter. The resulting waveform was processed in Matlab using various spectral analysis techniques (FFT and AR). Our preliminary results show that a relative ratio analysis (low frequency power/high frequency power) for both the raw PPG signal and its derived pulse statistics (height, beat-to-beat interval) is a useful technique for detecting change in sympathetic tone resulting from positional change. PMID- 17271677 TI - Optimal wavelets for electrogastrography. AB - Matching a wavelet to class of signals can be of interest in feature detection and classification based on wavelet representation. The aim of this work is to provide a quantitative approach to the problem of matching a wavelet to electrogastrographic (EGG) signals. Visually inspected EGG recordings from sixteen dogs and six volunteers were submitted to wavelet analysis. Approximated wavelet-based versions of EGG signals were calculated using Pollen parameterization of 6-tap wavelet filters and wavelet compression techniques. Wavelet parameterization values that minimize the approximation error of compressed EGG signals were sought and considered optimal. The wavelets generated from the optimal parameterization values were remarkably similar to the standard Daubechies-3 wavelet. PMID- 17271678 TI - Analysis on synchronous time-frequency components of human movement related cortical potential using wavelet transform. AB - Electroencephalogram (EEG) has been generally known as a non-destructive method to examine the function of human brain. In recent years, brain-computer interface (BCI) based on EEG has been a growing field of research and development. This work presents to identify time frequency components of movement-related cortical potential (MRCP) associated with the human voluntary muscle behaviors using the wavelet transform. The EEG was recorded with the 5-channel referential derivations, Fz, Cz, C3, C4, Pz, referenced to the right earlobe based on the international 10-20 system. The voluntary activity was recorded with the electrode placed on the palm side of the metacarpophalangeal joint when the subjects flexed the right - or left - hand index finger respectively and eyes closed. The synchronous time-frequency components of MRCP were shown in this study. PMID- 17271679 TI - Timing events in Doppler ultrasound signal of fetal heart activity. AB - Among various methods of monitoring fetal heart activity a Doppler ultrasound technique is the most often used. Complexity and variability of Doppler signal make difficult the precise measurement of timing dependences defining individual phases of cardiac cycle. Aim of the work was to carry out detailed comparative analysis of Doppler echo coming from movement of two different objects within fetal heart: valve and wall. Joint time frequency analysis were applied. Fetal monitor performed a role of input device in our measurement station based on LabView environment. Doppler signal was acquired from analog outputs with a help of dedicated data acquisition card. Average recording time in a group of 15 patients was 20 minutes. Analysis comprised determination and comparison of spectrograms and power density spectrums corresponding to individual phases of cardiac cycle. PMID- 17271680 TI - The SEMG analysis for the lower limb prosthesis using wavelet transformation. AB - Wavelet transformation (WT) and wavelet packet transformation (WPT) are used in this paper to eliminate the noises of surface EMG sampled from the lower limb during the subjects of study walked normally on the flat. By comparing the denoise result, WPT wins an advantage of WP with the same threshold. And the result shows that if the suitable scale and the threshold are selected, the high frequency noises can be eliminated effectively. According to the characteristic of WPT, the motion features are extracted during the stance phase and the swing phase using the WPT. The figures show the fine extraction result in this paper. PMID- 17271681 TI - Ambulatory electroencephalographic monitoring system for the analysis of brain waves. AB - This work is concerned with the development of a special equipment to monitor the brain waves of the patients even when he is under mobility in his locality and transmit them to the hospital or any monitoring station and record the electroencephalogram (EEG) of those patients and to diagnose the presence of epileptic seizures if any with an intelligent software and to store these details which may be useful for further analysis or expert consultations. This may prove very useful for the epileptic patients especially when the patient develops occasional problems related to his neural activities; bedside monitoring is not feasible both physically and economically. Under such conditions, ambulatory electroencephalographic monitoring provides an efficient and effective solution for this problem. This unit is equipped with a sophisticated hardware to acquire, amplify and transmit EEG and receive them through an interface unit and a software module to denoise and analyse them with epileptic seizure and spike detection algorithms coded with discrete wavelet transformation technique. PMID- 17271682 TI - Extraction of features in EEG signals with the non-stationary signal analysis technology. AB - The efficient detection of feature waves of EEG signals can provide more proof in clinic diagnose for doctors, then improve the veracity of diagnosis. In the course of studying the EEG, all kinds of measurement and analysis methods in time domain and frequency domain have been used in clinic, and the validity of some time-frequency testing methods to be applied to detect and analyze the feature waves of EEG waves have been discussed in theory, but which have not been found in clinic. From the view of clinic application and science investigation, all kinds of time-frequency testing and analysis methods such as Gabor transform, Wigner distribution, Choi-Williams distribution and wavelets transform have been integrated into the "virtual EEG measurement and analysis instrument" for detecting the feature waves of EEG signals. It is indicated that the satisfied results can be obtained by select different time-frequency testing and analysis methods based on the different purposes and feature waves. PMID- 17271683 TI - A signal analysis algorithm for determining brain compliance non-invasively. AB - Patients with increased intracranial pressure (ICP) caused by hydrocephalus or brain injury have poor brain compliance or increased brain stiffness. The condition is commonly treated by a surgical diversion of cerebrospinal fluid (CSF) through placement of a ventriculoperitoneal (VP) shunt. These inserted devices frequently fail and require replacement. Assessment of failed devices typically requires an invasive surgical procedure to implant an ICP sensor. Brain compliance can be determined non-invasively by comparing the intracranial pressure (ICP) waveform to the digital artery waveform. The ICP waveform is derived from a piezo sensor snugged into the external ear canal and worn as a headset. The digital artery waveform is derived from a stand pulse oximeter. Digital signal processing performed on sampled data from these two sensors shows a time-lag or phase relationship between the two waves which widens with worsening brain stiffness or compliance. An algorithm is presented that shows how these signals can be used to compute brain compliance. An instrument designed to calculate real-time brain compliance to aid healthcare professionals is described. PMID- 17271684 TI - Detecting tremors in microelectrode recordings without using a spike detector. AB - Tremor detection in extracellular neuronal recordings has required spike detection because tremors in extracellular neuronal recordings are caused by the fluctuation of action potential's firing rate. This work describes an automatic tremor detection algorithm of extracellular neuronal recordings without using a spike detector. The new algorithm is robust to noise and its performance is not affected by various morphologies of action potentials. PMID- 17271685 TI - Hybrid processing and time-frequency analysis of ECG signal. AB - A new simple approach basing on the histogram and genetic algorithm(GA) to efficiently detect QRS-T complexes of the ECG curve is described, so as to easily get the P-wave (when AF does not happen) or the f-wave (when AF happens). By means of signal processing techniques such as the power spectrum function, the auto-correlation function and cross-correlation function, two kinds of ECG signal when AF does or does not happen were successively analyzed, showing the evident differences between them. PMID- 17271686 TI - Cardiac arrhythmias predictive detection methods with wavelet-SVD analysis and support vector machines. AB - We expand the idea to develop new bio-signal processing tools that could predict possibility of future risk of abnormalities in ECG signals. The goal is to detect an inherent defect hidden in an ECG signal using wavelet analysis and support vector machines. We apply singular value decomposition analysis of spectral energy distribution in time-frequency plane to extract features, which is essentially independent of the actual duration of each event. We then classify the life threatening cardiac arrhythmias using support vector machines. We also investigate robustness of the developed system under presence of continuous Gaussian white noise. We obtained 92% sensitivity and 75% specificity for clean data and 81% sensitivity and 62% specificity for noisy data on our database. The proposed method could assist the health care professionals by earlier prediction of a disease and hence could facilitate in patient management, i.e., to provide a proper treatment for prevention or reduction of the future risk. PMID- 17271687 TI - Evaluation of the performance of a QRS detector for extracting the heart interbeat RR time series from fetal magnetocardiography. AB - Fetal magnetocardiography is a useful technique for non-invasive diagnostics of the electrophysiological activity of the fetal heart. The purpose of this study was to acquire fetal magnetocardiograms (FMCG) in a magnetically shielded environment as well as in a high-frequency noise environment, implement a QRS detection algorithm, and evaluate its performance. The FMCG were recorded over a period of 5 minutes at several sensor locations above the pregnant abdomen by second-order SQUID gradiometers. Quantitative analysis of FMCG with normal pregnancies and gestational ages 26-35 weeks showed improved QRS detection performance with signal pre-processing and parameter tuning. PMID- 17271688 TI - Chronic stress evaluation using neuro-fuzzy. AB - The purpose of this research was to evaluate chronic stress using physiological parameters. Wistar rats were exposed to sound stress for 14 days. Biosignals were acquired hourly. To develop a fuzzy inference system that can integrate physiological parameters, the parameters of the system were adjusted by the adaptive neuro-fuzzy inference system. Of the training dataset, the input dataset was the physiological parameters from the biosignals and the output dataset was the target values from the cortisol production. Physiological parameters were integrated using the fuzzy inference system, then 24-hour results were analyzed by the Cosinor method. Chronic stress was evaluated from the degree of circadian rhythm disturbance. Suppose that the degree of stress for initial rest period was 1. Then, the degree of stress after 14-day sound stress increased to 131, and increased to 1.47 after the 7-day recovery period. That is, the rat was exposed to 37%increased amount of stress by the 14-day sound and did not recover after the 7-day recovery period. PMID- 17271689 TI - Accurate, noninvasive measurement of total hemoglobin concentration with optoacoustic technique. AB - The measurement of total hemoglobin concentration is currently invasive and time consuming. The optoacoustic technique may provide accurate and noninvasive measurements of total hemoglobin concentration by probing blood vessels. We studied the influence of blood vessel diameter and lateral displacement of the optoacoustic probe on accuracy of total hemoglobin concentration measurements with this technique. PMID- 17271690 TI - Analysis of optical recording stability using wavelet entropy of action potentials. AB - A method based on wavelet entropy is presented for analysis of optically recorded action potentials to assess stability of the experiment. The action potentials are recorded using fluorescent voltage-sensitive dye di-4-ANEPPS by optical means. The acquired signals are preprocessed using averaging with filtered residue method and decomposed by continuous wavelet transform. Entropy is then computed using the wavelet coefficients. Wavelet entropy helps to detect possible amplitude and frequency changes in the signals caused by photo-bleaching. PMID- 17271691 TI - A novel method of estimation of DPOAE signals. AB - A new method of measurement of DPOAE signal level based on a recently introduced nonlinear adaptive method of extraction of nonstationary sinusoids is presented. Essentially, three units of such an algorithm are employed to extract and measure the two stimuli and the DPOAE signal. Each unit has the capability of locking on a specified sinusoidal component of the input signal and tracking its variations over time. Performance of the proposed method is demonstrated with the aid of computer simulation and is verified in laboratory using recorded clinical data. Comparison is made between the proposed technique and existing methods. The proposed method features structural simplicity which renders it particularly attractive for implementation on both software and hardware platforms. It offers a high degree of immunity with regard to background noise and parameter variations. Compared to conventional methods, the proposed method offers a shorter measurement time which is of significant value in clinical examinations. PMID- 17271692 TI - Wavelet analysis of surface electromyography signals. AB - A number of digital signal processing (DSP) techniques are being applied to surface electromyography (SEMG) signals to extract detailed features of the signal. Fast Fourier transform (FFT) is one of the most common methods for analyzing the signal whether it is filtered or not. Another DSP technique is referred to as wavelet analysis, a method that is gaining more use in analyzing SEMG signals. This research focuses on using the discrete wavelet transform (DWT) and the wavelet package transform (WPT). Both DWT and WPT use analytical wavelets called "mother wavelet" which comes in different sets or "families". Wavelet analysis has the advantage over FFT as it provides the frequency contents of the signal over the time period that is being analyzed. SEMG signals were collected from a muscle under sustained contractions for 4 seconds with different loads. The raw signals were analyzed using FFT, DWT and WPT in LabVIEW(R) using its signal processing toolset. Using wavelet analysis the SEMG signal was decomposed into its frequency content form and then was reconstructed. In this paper the results are presented to show that certain families of mother wavelets of wavelet analysis are more suitable than others for analyzing SEMG signals. PMID- 17271693 TI - Copula-based positive time-frequency distributions of the phonocardiogram. AB - This paper introduces a method for time-frequency analysis of the phonocardiogram. The proposed method is a modified version of the copula-based technique, which constructs positive time-frequency distributions, so as to be suitable for the analysis of periodically stationary random processes. The copula based time-frequency distributions have some desirable properties: positivity, correct marginals and low computational cost. We use averaged spectrogram as a template in copula-based technique in order to construct a positive time frequency distribution of the phonocardiogram. Results clearly show that the copula-based time-frequency distributions have much better resolution in time and frequency domain than the spectrogram does. Positivity and high resolution depend on the marginals of the distributions will offer excellent potential for estimating local parameters of the distributions, like a instantaneous frequency or instantaneous equivalent bandwidths using Renyi's divergence formulated by the authors. PMID- 17271694 TI - Removal of EMG and ECG artifacts from EEG based on wavelet transform and ICA. AB - In this study, the methods of wavelet threshold de-noising and independent component analysis (ICA) are introduced. ICA is a novel signal processing technique based on high order statistics, and is used to separate independent components from measurements. The extended ICA algorithm does not need to calculate the higher order statistics, converges fast, and can be used to separate subGaussian and superGaussian sources. A pre-whitening procedure is performed to de-correlate the mixed signals before extracting sources. The experimental results indicate the electromyogram (EMG) and electrocardiograph (ECG) artifacts in electroencephalograph (EEG) can be removed by a combination of wavelet threshold de-noising and ICA. PMID- 17271695 TI - Adaptive interference cancel filter for evoked potential using high-order cumulants. AB - This paper is to present evoked potential (EP) processing using adaptive interference cancel (AIC) filter with second and high order cumulants. In conventional ensemble averaging method, people have to conduct repetitively experiments to record the required data. Recently, the use of AIC structure with second statistics in processing EP has proved more efficiency than traditional averaging method, but it is sensitive to both of the reference signal statistics and the choice of step size. Thus, we proposed higher order statistics-based AIC method to improve these disadvantages. This study was experimented in somatosensory EP corrupted with EEG. Gradient type algorithm is used in AIC method. Comparisons with AIC filter on second, third, fourth order statistics are also presented in this paper. We observed that AIC filter with third order statistics has better convergent performance for EP processing and is not sensitive to the selection of step size and reference input. PMID- 17271696 TI - Biopattern initiative: towards the development and integration of next-generation information fusion approaches. AB - Even though significant technological advances have been achieved and applied in the medical field from a computational point of view, there is still a significant lag in effectively correlating diverse information sources towards the facilitation of clinical reasoning and improved decision making. In order to address this gab, the biopattern network is oriented towards the efficient information sharing and flow among the various expert groups in the network, in a consistent and expertise-independent fashion. The major effort is focused towards integrating technology for the emerging areas of bioinformatics and the joint consideration of information from medical-, neuro- and bio-informatics. One of Biopattern's pathology areas is brain diseases. Special attention is paid not only in organizing the existing (widely applied) techniques, but also in the development of next-generation technological approaches. The target of new developments is in algorithmic solutions for fusion of information from heterogeneous signal sources like MRI and EEG that may function in a consummative way. This work summarizes the project objectives and intended directions, with emphasis to brain diseases. PMID- 17271697 TI - Dipole source localisation using independent component analysis: single trial localisation of laser evoked pain. AB - The accuracy of the inverse solution that finds the spatial location of the generating sources from averaged scalp-recorded event related potentials (ERPs) relies on assumptions about the ERP signals and the sources. We provide evidence that using independent component analysis (ICA) as a signal decomposition filter prior to applying the inverse solution reveals sources that cannot be detected by conventional source localisation methods. Five clusters of sources emerged: a single source cluster in caudal cingulate and bilateral sources in secondary somatosensory cortex (SII), inferior parietal cortex, premotor cortex and insular cortex. The locations of the source dipoles were consistent with findings using fMRI and PET but have not all been previously detected in a single electrophysiological study. In addition, the time-course of the activation of these dipoles was estimated. The results suggest that using ICA to localise single trial data is a powerful tool for exploring the spatiotemporal dynamics of rapid and complex brain processes. PMID- 17271698 TI - Does the combination of magnetic resonance imaging and spectroscopic imaging improve the classification of brain tumours? AB - Magnetic Resonance Imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) play an important role in the noninvasive diagnosis of brain tumours. We investigate the use of both MRI and MRSI, separately and in combination with each other for classification of brain tissue types. Many clinically relevant classification problems are considered; for example healthy versus tumour tissues, low- versus high-grade tumours. Linear as well as nonlinear techniques are compared. The classification performance is evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). In general, all techniques achieve a high performance, except when using MRI alone. For example, for low- versus high-grade tumours, low- versus high-grade gliomas, gliomas versus meningiomas, respectively a test AUC higher than 0.91, 0.93 and 0.98 is reached, when both MRI and MRSI data are used. PMID- 17271699 TI - The role and efficacy of non-linear models in decision making and prognostication. AB - In few types of cancer, genomic abnormalities have been linked to the phenotype and carcinogenesis with a degree of precision. For most cancers, however, this is not the case and the literature provides no clear indication of any logical process. The main difficulties are the great redundancy within the genome and proteome, the vast number of interconnections and the vast number of feedback loops. Such complicated systems can be modelled, but will require highly sophisticated analysis using computational mathematics techniques. Neural networks have been in common use in medical research for the past 20 years. They have been used for classification and for prediction of hazard or failure but are still not widely used for explanation. The binary output can be modified by, for example, adding a Bayesian function to the output stage so that survival probabilities can be given. We looked at the application of probabilistic neural networks in providing prognosis in two types of cancer; laryngeal carcinoma which has a relatively short hazard time and a medium survival rate and ocular melanoma with longer hazard time and higher survival rate. We compared their performance with the more traditional methods and studied their limitations and boundaries. PMID- 17271700 TI - A new system theoretic classifier for detection and prediction of epileptic seizures. AB - A system theoretic computational approach has been recently proposed as a generalization of probabilistic networks for modeling complex systems. The computational approach, fuzzy measure-theoretic quantum approximation of an abstract system (FMQAS), generates a system measure between each pair of system objects as a relative measure of association incorporating, through a hierarchical iterative procedure, both the local and global significance of the interaction. FMQAS provides the basis for a new classification algorithm. A preliminary modification of this classification algorithm for temporal sequences is used to analyze electroencephalogram (EEG) data obtained in the temporal neighborhood of a seizure episode to obtain distinct state descriptions (patient invariant characterizations) of the seizure states. This state characterization enables seizure detection before onset with sufficient time to warn the individual or execute actions to abort the seizure formation. PMID- 17271701 TI - Patient-specific seizure onset detection. AB - This paper presents an automated, patient-specific method for the detection of epileptic seizure onsets from noninvasive EEG. We adopt a patient-specific approach to exploit the consistency of an individual patient's seizure and non seizure EEG. Our method uses a wavelet decomposition to construct a feature vector that captures the morphology and spatial distribution of an EEG epoch, and then determines whether that vector is representative of a patient's seizure or non-seizure EEG using the support-vector machine classification algorithm. Our completely automated method was tested on non-invasive EEG from thirty-six pediatric subjects suffering from a variety of seizure types. It detected 131 of 139 seizure events within 8.0+/-3.2 seconds following electrographic onset, and declared 15 false-detections in 60 hours of clinical EEG. Our patient-specific method can be used to initiate delay-sensitive clinical procedures following seizure onset; for example, the injection of an imaging radiopharmaceutical or stimulation of the vagus nerve. PMID- 17271702 TI - Quantifying and visualizing uncertainty in EEG data of neonatal seizures. AB - This paper presents an approach to quantifying and visualizing uncertainty in EEG data of neonatal seizures. This approach exploits the inherent ability of trained quantum neural networks (QNNs) to learn arbitrary membership profiles from sample data. The ability of QNNs to quantify uncertainty in data is combined with the ability of ordered self-organizing maps (SOMs) to recognize structure in data and allow its visualization in two dimensions. The proposed approach is evaluated using EEG data of neonates monitored for seizures. PMID- 17271703 TI - A radial basis function neural network for single sweep detection of somatosensory evoked potentials. AB - The aim of this research is to evaluate the effectiveness of the employment of a Gaussian radial basis function neural network (RBFNN) for the on-line detection of single sweep somatosensory evoked potentials (SswSEPs), paying particular attention to the capability of tracking trial-to-trial variabilities. On the basis of simulations the parameters of the network have been set and the results have then been compared with those obtained from other methods, in particular with the ensemble averaging, the moving window averaging and the ARX filtering. This research shows a better performance of the RBFNN, because it is able to follow changes of the underlying signal even in noisy conditions and does not require prior assumptions. PMID- 17271704 TI - BP-neural network based-characterization of electrographic magnetohydrodynamic signals in MR. AB - Electrocardiographs (ECG) signal collected during magnetic resonance (MR) imaging is affected by signal artifact because magnetic fields produce competing signals, from moving conductors in the large vessels. That is called the magnetohydrodynamic effect, which makes it difficult to recognize ST-T changes from ECG signal collected in a magnetic field (MRI). Resolving that problem is important both for accurate triggering (elimination of false triggers from tall peaked T waves) and for monitoring (identifying if or when patient develops ischemia or myocardial injury). This work describes an algorithm based on neural network that is designed to cancel this artifact for ECG signal acquired during MR imaging. PMID- 17271705 TI - Semi-supervised learning of probabilistic models for ECG segmentation. AB - We present a novel semi-supervised learning algorithm, based upon the EM algorithm for maximum likelihood estimation, which can be used to learn probabilistic models from subjectively labelled data. We demonstrate the method on the task of automated ECG segmentation, with a particular emphasis on the accurate measurement of the QT interval. In addition we discuss the use of wavelet methods for the representation of the ECG, and advanced duration modelling techniques for hidden Markov models applied to ECG segmentation. PMID- 17271706 TI - Real time monitoring of ischemic changes in electrocardiograms using discrete Hermite functions. AB - A novel scheme for real time detection of ischemic features from long term electrocardiograms (ECG), based on the dilated discrete Hermite expansion is proposed. The discrete Hermite functions used for the expansion are eigenvectors of a symmetric tridiagonal matrix that commutes with the centered Fourier matrix. The ECG signals were expanded in terms of Hermite functions using a simple dot product. The resulting coefficients were found to have details about the shape of the ECG signal. The first 50 coefficients had all sufficient information to reconstruct the ECG signal with acceptable percentage RMS difference (PRD). A committee neural network classifier with these 50 input parameters was trained to identify ischemic features, namely ST segment and T wave changes. A sensitivity of 98% and a specificity of 97.3% were achieved. A comparison of these figures with other contemporary classification schemes revealed a superior performance. PMID- 17271709 TI - Application of the evidence framework to brain-computer interfaces. AB - A brain-computer interface (BCI) is a communication system, that implements the principle of "think and make it happen without any physical effort". This means a BCI allows a user to act on his environment only by using his thoughts, without using peripheral nerves and muscles. Nearly all BCIs contain as a core part a machine learning algorithm, which learns from training data a function, that can be used to discriminate different brain activities. In the present work we use a Bayesian framework for machine learning, the evidence framework [1], [2] to develop a variant of linear discriminant analysis for the use in a BCI based on electroencephalographic measurements (EEG). Properties of the resulting algorithm are: a) a continuous probabilistic output is given, b) fast estimation of regularization constants, and c) the possibility to select among different feature sets, the one which is most promising for classification. The algorithm has been tested on one dataset from the BCI competition 2002 and two datasets from the BCI competition 2003 and provides a classification accuracy of 95%, 81%, and 79% respectively. PMID- 17271708 TI - Sleep-wake identification in infants: heart rate variability compared to actigraphy. AB - Heart rate variability and actigraphy offer alternative techniques for sleep-wake identification compared to manual sleep scoring from a polysomnograph. The advantages include high accuracy, simplicity of use, and low intrusiveness. These advantages are valuable for determining sleep-wake states in such highly sensitive groups as infants. A learning vector quantization neural network was tested as a predictor. The accuracy of the neural network was compared to "gold standard" hand-scored polysomnographs. The prediction results are in agreement with other studies, thus validating the suggested methodology. PMID- 17271710 TI - Bayesian radial basis function network for modeling fMRI data. AB - Noisy and nonlinear nature make fMRI signal processing a challenging problem. We proposed and analyzed the Bayesian trained radial basis function (RBF) neural network in fMRI data processing. The method, which determines the regularization parameter in RBF network automatically by Bayesian learning, is especially suitable for fMRI data processing. Both simulated and real fMRI data were tested. Results show that this approach could model fMRI signals and remove the slowly varying drift in the data sets as well. PMID- 17271711 TI - Detection of suspicious lesions in dynamic contrast enhanced MRI data. AB - Dynamic contrast-enhanced magnet resonance imaging (DCE-MRI) has become an important source of information to aid breast cancer diagnosis. Nevertheless, next to the temporal sequence of 3D volume data from the DCE-MRI technique, the radiologist commonly adducts information from other modalities for his final diagnosis. Thus, the diagnosis process is time consuming and tools are required to support the human expert. We investigate an automatic approach that detects the location and delineates the extent of suspicious masses in multi-temporal DCE MRI data sets. It applies the state-of-the-art support vector machine algorithm to the classification of the short-time series associated with each voxel. The ROC analysis shows an increased specificity in contrast to standard evaluations techniques. PMID- 17271712 TI - Fast detection of wave V in ABRs using a smart single sweep analysis system. AB - The analysis of auditory brainstem responses (ABRs) is accepted to be the most reliable method for the objective diagnosis and quantification of hearing loss in newborns. However, in currently available setups, a large number of sweeps has to be averaged to obtain a meaningful signal at low stimulation levels due to a poor signal-to-noise ratio. In this study, we present a new approach to the detection of wave V in ABRs using a smart single sweep analysis system. A small number of sweeps is decomposed by optimized tight frames and evaluated by a kernel based novelty detection machine. This hybrid supervised learning scheme is combined with an intersweep dissimilarity tracing for the final decision making. At the challenging stimulation level of 30 dB, our system reached a reasonable specificity and sensitivity for the detection of wave V in a fraction of the measurement time of conventional schemes. PMID- 17271713 TI - Identification of fetal sufferance antepartum through a multiparametric analysis and a support vector machine. AB - The present work is concerned with the automatic identification of fetal sufferance in intrauterine growth retarded (IUGR) fetuses, based on a multiparametric analysis of cardiotocographic recordings feeding a neural classifier. As classification tool, we propose a SVM (support vector machine), which receives the set of linear and nonlinear parameters extracted from the fetal heart rate signal (FHR) as input and gives the indication of fetal distress as output. SVM is a powerful supervised learning algorithm belonging to the statistical learning theory. It minimizes the structural risk performance in various classification problems. Three SVMs are built with different kernels. Their training set includes 70 cases: 35 normal and 35 IUGR suffering fetuses. Classification results obtained with a 2nd order polynomial kernel, on a test set of 30 unknown cases, show good values of accuracy, specificity and sensitivity. The SVM performance is very similar to that obtained with multilayer perceptron and neurofuzzy classifiers proposed in previous works. The introduction of a hybrid unsupervised/supervised learning scheme integrating independent component analysis (ICA) with SVM will be the natural development of this work with a further improvement of the diagnostic ability of the system. PMID- 17271714 TI - Novel approach for spastic hemiplegia classification through the use of support vector machines. AB - The use of computer based classification methods for spastic hemiplegia (SH) is a relatively new approach. Before and still, the classification is primarily done by specialized physicians through manual template matching on kinematics plots of the sagittal plane data from the affected limb generated by gait laboratories. In the past, several methods for computer based automation of this classification have been attempted. This paper introduces the use of support vector machine (SVM) as a model that contributes to this process. The results obtained from the use of SVM are quite efficient considering the data set utilized involves patients from an array of ages and both sex. It should be mentioned that even though the number of patients is not trivial; the percentages of accurate classification represented are promising. Since the SVM method improves its accuracy with an increased number of training cases, this approach has the advantage of becoming more accurate with time. Many more significant discoveries are expect from the introduction of SVM in the analysis of SH and further studies of gait related pathologies are expected to contribute as well. PMID- 17271715 TI - Evaluation of a device scoring classes of hemorrhagic shock. AB - In order to evaluate the feasibility of a device scoring classes of hemorrhagic shock, a multivariate analysis of physiological data collected on swine enduring continuous blood loss was conducted. Raw data sampled at up to 500 Hz were first preprocessed and used for features extraction over period of 1 mm. An expert scored all these physiological features, into one of the four classes of hemorrhagic shock: none, compensated, uncompensated and irreversible. A supervised learning of various classifiers was then evaluated over these data. The percentage of misclassification obtained when using a realistic way of estimating error (a leave one -animal- out validation) is about 20% when mean arterial pressure is used, and about 40% when only non invasive features are used. The results are about the same whatever the classifiers used. This evaluation is discussed and a visualization is proposed in order to assess the temporal supervision given by the classifiers. PMID- 17271716 TI - Continuous classifier training for myoelectrically controlled prostheses. AB - Myoelectrically controlled prostheses use pattern recognition systems to classify input motions. Typically, these systems are initially trained offline using a set of training data. Changing conditions cause an increase in signal variation, leading to higher error rates. For better adaptability, a continuously trained classifier was developed. Data with valid class decisions are used to retrain the classifier with the class decisions used as classification targets. In this implementation the classifier validates decisions by using a retraining buffer to locate consecutive, identical majority vote decisions. Retraining is performed by incorporating new valid feature vectors, selected from the retraining buffer, into the training set, while discarding older vectors. Using the continuously trained classifier, an average improvement of 2.57% was seen over the noncontinuously trained classifier. PMID- 17271717 TI - Capacity of the horizontal vestibuloocular reflex motor learning in goldfish. AB - The vestibuloocular reflex (VOR) stabilizes visual image on the retina during head motion by counter-rotating the eyes in the orbit. It indicates a type of learning called motor learning by which changes in system characteristics due to development, aging etc. are adaptively compensated to achieve visual stabilization. Presently, we evaluated the capacity of the horizontal VOR motor learning in goldfish to argue the limitation in their learning ability and to identify the neuronal sites that is capable of achieving the learning task. We demonstrate that goldfish VOR can be modified in the opposite directions for right and leftward head rotations simultaneously. The roles of cerebellum to achieve this learning are discussed. PMID- 17271718 TI - Using lung sounds in classification of pulmonary diseases according to respiratory subphases. AB - Auscultation-based diagnosis of pulmonary disorders relies heavily on the presence of adventitious sounds and on the altered transmission characteristics of the chest wall. The phase information of the respiratory cycle within which adventitious sounds occur is very helpful in diagnosing different diseases. In this study, respiratory sound data belonging to four pulmonary diseases, both restrictive and obstructive, along with healthy respiratory data are used in various classification experiments. The sound data are separated into six subphases, namely, early, mid, late inspiration and expiration and classification experiments using a neural classifier are carried out for each subphase. The AR parameters acquired from segmented sound signals, prediction error and the ratio of expiration to inspiration durations are used to construct the feature set to the neural classifier. Classification experiments are carried out between healthy and pathological sound segments, between restrictive and obstructive sound segments and between two different disease sound segments. The results indicate that the classifier performance demonstrates subphase dependence for different diseases. These results may shed light in eliminating redundant feature spaces in building an expert system using lung sounds for pulmonary diagnosis. PMID- 17271719 TI - Learning arm's posture control using reinforcement learning and feedback-error learning. AB - In this paper, we propose a learning model using the Actor-Critic method and the feedback-error-learning scheme. The Actor-Critic method, which is one of the major frameworks in reinforcement learning, has attracted attention as a computational learning model in the basal ganglia. Meanwhile, the feedback-error learning is learning architecture proposed as a computationally coherent model of cerebellar motor learning. This learning architecture's purpose is to acquire a feed-forward controller by using a feedback controller's output as an error signal. In past researches, a predetermined constant gain feedback controller was used for the feedback-error-learning. We use the Actor-Critic method for obtaining a feedback controller in the feedback-error-earning. By applying the proposed learning model to an arm's posture control, we show that high performance feedback and feed-forward controller can be acquired from only by using a scalar value of reward. PMID- 17271720 TI - A study on the factor number determination methods in the partial least squares model for the urinalysis using Raman spectroscopy. AB - As an effort for the development of the nonintrusive measurement system, Raman spectroscopy was applied for the urinalysis. By using Raman spectroscopy, the concentration of the urine components could be measured. As a multivariate method, the partial least squares method was performed. When composing a calibration model, the determination of the appropriate number of factors was very important for the accurate prediction of the constituent concentration. In this study, the number of factors was determined by observing the minimum PRESS (prediction residual error sum of squares) value and the biggest correlation coefficient between the predicted values and the original values of the training set. After obtaining the most suitable number of factors by the two methods, the unknown constituent concentration was predicted with those factors, and the correlation coefficients between the pre-examined value and the predicted results from the unknown spectra were calculated. The analysis results using the two factor number determination methods were compared in order to determine which one is more suitable for the accurate urine component concentration prediction. The selected method will be used in the urinalysis using Raman spectroscopy system which will be one of the non-intrusive measurement systems in a live-alone patient's house. PMID- 17271721 TI - Constrained RLS algorithm for narrow band interference rejection from EEG signal during CES. AB - The filtering of signals in the presence of a narrow-band interference noise is a common problem in biomedical signal processing. A double adaptive band-rejection filter is applied to an electroencephalographic (EEG) signal corrupted by a double narrow-band white Gaussian noise during cranial electrical stimulation (CES). The multiple adaptive IIR digital band-rejection filters are designed by the pole-zero placement on the unit circle method using a unique second-order filter structure. Multiple band-rejection filters (of order 2N) can be designed by cascading N second-order band-rejection filters. The coefficients of the multiple band-rejection filters are calculated by convoluting the coefficients of the second-order band-rejection filters. The pole-zero placement on the unit circle method relates the coefficients of the filter through fundamental coefficients that are assumed to be independent. These coefficients are updated through the recursive least-squares (RLS) algorithm. Unlike other RLS based multiple adaptive band-rejection filters, the new constrained RLS (CRLS) multiple adaptive HR band-rejection filter truly adapts its zeros and poles. PMID- 17271722 TI - EEG features extraction using neuro-fuzzy systems and shift-invariant wavelet transforms for epileptic seizures diagnosing. AB - Electro-encephalogram Spikes Classification and latency computing is one of the important tools in epilepsy diagnosing. However, overlapped spikes cause complexity in problem solving. We use neuro-fuzzy systems and shift-invariant wavelet transforms to solve this problem. It has been shown that our suggested procedures have high-resolution and are able to classify and perform latency computing of overlapped spikes. PMID- 17271723 TI - Multi-spectral imaging and analysis for classification of melanoma. AB - Wavelengths in the visible spectrum are selected for multi-spectral trans illumination imaging of the skin lesions using the Nevoscope. The multi-spectral image data is analyzed using crisp and fuzzy partitioning techniques for classification of melanoma. It is shown that the multi-spectral images add the lesion depth and structural information to the superficial lesion characteristics obtained from the surface illumination images and hence, improve the sensitivity and specificity of melanoma diagnosis. PMID- 17271724 TI - Classification of mental tasks using fixed and adaptive autoregressive models of EEG signals. AB - Classification of EEG signals extracted during mental tasks is a technique for designing brain computer interfaces (BCI). We classify EEG signals that were extracted during mental tasks using fixed autoregressive (FAR) and adaptive AR (AAR) models. Five different mental tasks from 4 subjects were used in the experimental study and combinations of 2 different mental tasks are studied for each subject. Four different feature extraction methods were used to extract features from these EEG signals: FAR coefficients computed with Burg's algorithm using 125 data points, without segmentation and with segmentation of 25 data points, AAR coefficients computed with least-mean-square (LMS) algorithm using 125 data points, without segmentation and with segmentation of 25 data points. Multilayer perception (MLP) neural network (NN) trained by the backpropagation (BP) algorithm is used to classify these features into the different categories representing the mental tasks. The best results for FAR was 92.70% while for AAR was only 81.80%. The results obtained here indicated that FAR using 125 data points without segmentation gave better classification performance as compared to AAR, with all other parameters constant. PMID- 17271725 TI - Independent component extraction methods in biosignal processing. AB - The paper discusses methods for independent source identification within multiple channels electroencephalographical (EEG) signals recordings. The focus is to compare the independent component analysis (ICA) technique to a novel proposed method for individual components separation - the phase space method (PSM). Methods are suitable to be used for any multi-lead signal especially within biomedical signals processing area where independence is a key issue. PMID- 17271726 TI - An object-oriented toolbox for linear and nonlinear system identification. AB - Nonlinear system identification techniques are often used to construct mathematical models of physiological systems. There is a wide variety of model structures, many of which require specialized techniques for their identification. Unfortunately, this variety may present a significant barrier to any non-specialists who wish to use these methods. This work describes a MATLAB based toolbox that addresses these problems by providing a common environment supporting a robust set of tools for the identification, simulation, and manipulation of important model structures. The design philosophy and its implementation are described. An illustrative example, constructing a parallel cascade model of the dynamic stiffness of the human ankle, is used to demonstrate many of the features of the toolbox. PMID- 17271727 TI - A direct method of estimation of stimulus frequency otoacoustic emissions. AB - A novel technique of direct estimation of stimulus frequency otoacoustic emission (SFOAE) signals is proposed. SFOAE signals have been the subject of much research because of their value in providing information about the structure and health of the human auditory system. Current methods of estimation of SFOAE signals are indirect in the sense that the use of suppressor tones is inevitable and the SFOAE signals are estimated indirectly by virtue of a nonlinear residual time domain technique. Conventional signal processing techniques do not provide any means of direct estimation of SFOAE signals given that both the stimulus and the otoacoustic emission are at the same frequency. The studies conducted through testing of the proposed SFOAE estimation technique on simulated data show good performance of the proposed technique. PMID- 17271728 TI - Optimization of multi-frequency techniques used for cell membrane capacitance estimation. AB - Measurements of cell membrane capacitance serve as an indicator of cell membrane surface area and thus have traditionally been used in stimulus-secretion coupling to monitor exocytosis and endocytosis of secretory vesicles. In order to accurately monitor secretion, high-resolution methods of tracking small (10/sup 15/ F) changes in baseline capacitance must be utilized. Most presently used techniques require assumptions that are not appropriate under all recording conditions or suffer from a low signal-to-noise ratio (SNR). This paper proposes to improve upon current estimation techniques by developing an optimized multi frequency sinusoidal stimulus waveform for accurate capacitance estimations. The waveform is designed by jointly optimizing the phase and voltage of individual frequency components so as to minimize the theoretical bound on the variance of the capacitance estimate, while maintaining a preselected limit on the overall stimulus magnitude. PMID- 17271729 TI - Higuchi fractal dimension and spectral entropy as measures of depth of sedation in intensive care unit. AB - The ability of two easy-to-calculate nonlinear parameters, the Higuchi fractal dimension (HDf) and spectral entropy, to follow the depth of sedation in the intensive care unit is assessed. For comparison, the relative beta ratio is calculated. The results are evaluated using clinical assessment of the Ramsay score. The results show that the HD/sub f/ discriminates well between Ramsay scores 2-4 while beta ratio is superior for deeper levels of sedation. The value of the HD/sub f/ correlates highly with the cutoff frequency of the low-pass prefilter while spectral entropy is sensitive to the length of the analysis window. PMID- 17271730 TI - Flow SS-PARSE: a new method for rapid imaging and mapping of blood flow velocity. AB - A new method for flow velocity mapping of blood is presented here. Instead of the conventional approach of employing two images (velocity sensitive and control) to generate velocity information, in the new method the velocity is determined directly by solving an inverse problem. This technique is an application of single shot - parameter assessment by retrieval from signal encoding (SS-PARSE). Simulations have been done to demonstrate the feasibility of the method. The velocity measurement range of the prototype version is from -50cm/s to 50cm/s, roughly appropriate for future applications in blood flow measurement of carotid arteries. PMID- 17271731 TI - Improved algorithm for classification of ocular nystagmus. AB - An improved algorithm for classification of nystagmus was designed allowing the sorting of response segments even in severely non-linear patients and subjects with abnormally large phase shifts. The algorithm employs a model-based approach that was developed by Rey and Galiana. The improved classification algorithm consists of two essential stages. In the first stage the eye velocity response is classified to obtain initial estimates of the slow phase eye velocity intervals. In the second stage, the slow phase estimates are used to identify a response phase shift and nonlinearity, and compensate for their effects. Multiple tests on simulated data and experimental data obtained from clinical subjects are presented. The results of the tests demonstrate that the algorithm is able to analyze the patient data with a high accuracy even in the presence of noise, eye blinks and other artifacts. PMID- 17271732 TI - Accurate derivation of heart rate variability signal for detection of sleep disordered breathing in children. AB - The electrocardiogram (ECG) signal is used extensively as a low cost diagnostic tool to provide information concerning the heart's state of health. Accurate determination of the QRS complex, in particular, reliable detection of the R wave peak, is essential in computer based ECG analysis. ECG data from Physionet's Sleep-Apnea database were used to develop, test, and validate a robust heart rate variability (HRV) signal derivation algorithm. The HRV signal was derived from pre-processed ECG signals by developing an enhanced Hilbert transform (EHT) algorithm with built-in missing beat detection capability for reliable QRS detection. The performance of the EHT algorithm was then compared against that of a popular Hilbert transform-based (HT) QRS detection algorithm. Autoregressive (AR) modeling of the HRV power spectrum for both EHT- and HT-derived HRV signals was achieved and different parameters from their power spectra as well as approximate entropy were derived for comparison. Poincare plots were then used as a visualization tool to highlight the detection of the missing beats in the EHT method After validation of the EHT algorithm on ECG data from the Physionet, the algorithm was further tested and validated on a dataset obtained from children undergoing polysomnography for detection of sleep disordered breathing (SDB). Sensitive measures of accurate HRV signals were then derived to be used in detecting and diagnosing sleep disordered breathing in children. All signal processing algorithms were implemented in MATLAB. We present a description of the EHT algorithm and analyze pilot data for eight children undergoing nocturnal polysomnography. The pilot data demonstrated that the EHT method provides an accurate way of deriving the HRV signal and plays an important role in extraction of reliable measures to distinguish between periods of normal and sleep disordered breathing (SDB) in children. PMID- 17271734 TI - Spike sorting with support vector machines. AB - Spike sorting of neural data from single electrode recordings is a hard problem in machine learning that relies on significant input by human experts. We approach the task of learning to detect and classify spike waveforms in additive noise using two stages of large margin kernel classification and probability regression. Controlled numerical experiments using spike and noise data extracted from neural recordings indicate significant improvements in detection and classification accuracy over linear amplitude- and template-based spike sorting techniques. PMID- 17271733 TI - Analysis of the nonlinear autodependencies of respiratory pattern in patients on weaning trials. AB - Traditional time domain techniques of data analysis are often not sufficient to characterize the nonlinear dynamics of respiration. In this study, the respiratory pattern variability was analyzed using auto mutual information measures. These provide access to nonlinear statistical autodependencies of respiratory pattern variability. A group of 20 patients on weaning trials from mechanical ventilation were studied at two different pressure support ventilation levels, in order to obtain respiratory volume signals with different variability. Time series of breathing duration, inspiratory time, fractional inspiratory time, tidal volume and mean inspiratory flow were analyzed. Different measures based on auto-mutual information were studied to characterize the respiratory pattern variability with regard to its complex organization. PMID- 17271736 TI - Morphograms: exploiting correlation patterns to efficiently identify clinically significant events in intensive care units. AB - In this paper, we present a simple technique that utilizes the cross correlations between ECG signals and an arterial blood pressure (ABP) signal for the purpose of assessing signal quality and detecting artifacts in the ABP signal. The technique was tested using cases from a physician-annotated patient monitoring signal database from Beth Israel/Harvard-MIT University data bank. The results were encouraging: 45% of the manually annotated artifacts were correctly classified and 98% of the manually annotated true events were correctly classified. PMID- 17271735 TI - A theoretical study for the chaos and complexity of the synchronous oscillations in electrically coupled abnormal neurons. AB - Many experiments demonstrate that the synchrony of neurons is a hallmark in epileptic seizure and the dynamical process of the epilepsy is complex with new oscillations born. In fact, epileptic seizure is very complicated relating to many factors so that it can't be understood thoroughly only in some special aspect. Based on the previous work on synchronous oscillations of electrically coupled abnormal neurons, a theoretical effort is carried out to further investigate the chaos by Lyapunov exponent and phase portrait and degree of complexity by approximate entropy in the dynamical activities. It is concluded that the synchronous activities are chaotic and complex with new oscillations born and the values of Lyapunov exponent and approximate entropy are different with the electrical coupling strength. It is also found that the trend of approximate entropy is same as that of Lyapunov exponent in the study at the dynamical activity of the two electrical coupling neurons. In the synchrony of 2 D neuronal network, the values of Lyapunov exponent are almost much greater than that of the two electrical coupling neurons. The values of approximate entropy of the different neurons in the 2-D network have almost the same trend but approximate entropy of neuron in synchrony is greater than that of neuron in non synchrony. It is indicated that the neurons in synchrony have greater ability to produce new oscillations than that in non-synchrony. The theoretical work is helpful to understand the pathological mechanism of new oscillations born in epilepsy from a nonlinear point of view. PMID- 17271737 TI - Measures of linear and nonlinear interdependence of electrocortigram time series from evoked-response potential experiments. AB - In this brief discussion, we consider various coupling measures applied to electrocortigram (ECoG) data. The analysis consists of both linear and nonlinear measures of coupling - or interdependence - between two ensembles of measurements collected at two electrodes in an evoked-response potential (ERP) experiment. The interdependence measures are applied to simulated time series data and experimental ECoG data. The algorithms discussed here are implemented in the interactive data language (IDL) and available for download from the authors. PMID- 17271738 TI - Subband EEG complexity after global hypoxic-ischemic brain injury. AB - Hypoxic-ischemic (HI) brain injury after cardiac arrest (CA) causes the main morbidity and mortality of the patients. The mechanism of HI neurological injury and its real time detection and monitoring have been extensively studied in the past years. The electroencephalogram (EEG) following CA has been investigated to provide a noninvasive monitoring strategy. In this present work, we studied the complexity of the EEG signal after HI injury. Sample entropy (SampEn) is applied to analyze the EEG in different frequency bands (delta, theta, alpha and beta). The "alpha vulnerability" in rhythmic complexity is observed, which indicated that among different EEG rhythmic subbands, alpha wave shows a distinct SampEn decrease during the early recovery period after HI injury. The alpha vulnerability is confirmed by our previous research on the vulnerability in thalamic somatosensory pathway. The results may help us develop means to restore electrical function recovery after HI. PMID- 17271739 TI - Dual approach for automated sleep spindles detection within EEG background activity in infant polysomnograms. AB - An automated system for sleep spindles detection within EEG background activity, combining two different approaches, is presented. The first approach applies detection criteria on the sigma-band filtered EEG signal, including fuzzy thresholds. The second approach mimics an expert's procedure. A sleep spindle detection is validated if both approaches agree. The method was applied on a testing set, consisting of continuous sleep recordings of two patients, totaling 1132 epochs (pages). A total of 803 sleep spindles events were marked by the experts. Results showed an 87.7% agreement between the detection system and the medical experts. PMID- 17271740 TI - Nonlinear analysis in cognition process. AB - Cognition process is directly related to the brain functionality and is a dynamically changing system. Nonlinear analysis of EEG signals has been used as a means for studying the dynamical changes in cortical networks. In the course of cognition process, the activity complexity of the neuronal units is continually shifting. This phenomenon can be viewed with the topographic map and nonlinear EEG measures. The surrogate data method was used to show that EEG signals during cognitive activity are nonlinear. Additionally, we employ the compressed spectral array method to show that the gammaband EEG is closely related to cognitive processes. PMID- 17271741 TI - Spectral and bispectral analysis of the EEG rhythms in basal conditions and during photic stimulation. AB - The aim of the present study is the quantification of the relationships and the phase coupling among spectral peaks in the EEG signal at different sites of the scalp. 10 normal subjects underwent the study. The multi-channel EEG signal was recorded during basal conditions and during photic stimulation. The stimulation frequency (SF) has been chosen related to the single subject's spontaneous alpha rhythm (SF = alpha, SF = 2alpha, SF = alpha/2) and not related to the alpha rhythm (SF = 14 Hz). Spectral and bispectral analysis put into evidence that, in basal conditions, with closed eyes, the spontaneous alpha rhythm is generated by independent oscillators in the occipital and frontal regions. In addition the beta rhythm in the spectra seems an harmonic component linked to the former one. During photic stimulation the spontaneous alpha rhythm is drastically decreased, and the harmonics are lowered, while frontal and occipital responses seem to synchronize. In addition the frontal lobe seems able to generate sub-harmonics which could be related to the genesis of generalized seizures in predisposed subjects. PMID- 17271742 TI - Three EIT approaches for static imaging of head. AB - Three EIT approaches for static imaging of head are investigated in this paper. The modified Newton-Raphson (MNR) method and the differential evolution (DE) algorithm are applied to the impedance reconstruction of 2D section of head based on real head model. Comparisons are carried out on the results obtained using simulated data, and a DE-MNR combination method is proposed, which demonstrated high impedance reconstruction quality with fast convergence in the 2D EIT simulation for static imaging of head. PMID- 17271743 TI - Evaluation of ischemic states using bispectrum parameters of EEG and neural networks. AB - No doubt a noninvasive technique for detection of focal cerebral ischemic extent, before the focus is formed, is extremely valuable. This work presents a new approach to early evaluate the degree of focal ischemic injury by combining bispectrum estimation of electroencephalograms (EEGs) with artificial neural network (ANN). The graded ischemic injuries in 24 Sprague-Dawley (SD) rats were induced for different periods of 8, 18, 30 min. Four channels of EEG were collected in each rat at the scheduled time of ischemia. The maximum bicoherence index and the weighted center of EEG bispectrum (WCOB) were extracted from the EEG bispectrum and were used as the input feature vector of a four layer (12-7-2 1) ANN for prediction. Training and testing the ANN used the 'leave one out' strategy. The levels of ischemic injury were verified and classified by observing the ischemic area in the heat shock protein (HSP70) test. The proposed system was able to correctly detect the ischemic extent in average accuracy of 91.67% of the cases. The results show that the scheme can be expected to diagnose ischemic cerebral injury in its earlier phases. PMID- 17271744 TI - Characteristics of gait of humans with incomplete spinal cord injury. AB - Epidural spinal cord stimulation has been demonstrated to help the recovery of walking abilities of patients with incomplete spinal cord injury when combined with partial weight bearing therapy. However, no work has been done in studying the dynamics of these signals generated with and without stimulation. We show that the underlying dynamics of such signals is chaotic. We also estimate the correlation dimension of these signals and show the difference in the dynamics of gait with and without stimulation using the kinematic data of right knee and right hip. The correlation dimension thus estimated can be used to evaluate the efficiency of epidural spinal cord stimulation in patients. PMID- 17271745 TI - Approximate entropy analysis of electroencephalogram in vasovagal syncope on tilt table test. AB - Thirty vasovagal attacks on sublingual nitroglycerin stressed tilting test were selected. By the method of shifting window along the continuous EEG signals the linear (spectral power and coherence) and nonlinear (approximate entropy) EEG features of the whole course in the tilt table test were demonstrated. Of all the EEG parameters approximate entropy is a more sensitive index in clarifying stages of various degree of tilting stress and in identifying the syncopal transient. PMID- 17271746 TI - Linear and nonlinear analysis of electroencephalogram of the coma. AB - The coma is common in intensive care units. The bedside physical examination provides a means to measuring the neurological status, but it cannot be a continuous evaluation, whereas electroencephalogram (EEG) can reflect the immediate electrical activities of the brain. In this paper, we investigate the spectral parameters, complexity and irregular measures, and spectral entropy in the coma. Compared to the normal subject, the EEG of the coma has a dominance of slow wave, low complexity, less irregularity, and low spectral entropy. This result demonstrates the possibility to use EEG analysis for the monitoring of neurological function. PMID- 17271747 TI - A suppression of an impulsive noise in ECG signal processing. AB - The biomedical signals are commonly recorded with a noise. Many different kinds of noise exist in biomedical environment. One of the noises is a waveform of an electrical activity of muscles. This "natural" distortion is usually modeled with a white Gaussian noise. But such assumption is not always true, because real-life muscle noise has sometimes impulsive character. First objective of this paper is an application of the alpha-stable distribution as a model of the real-life muscle noise in the ECG signal. Second objective of this paper is an application of a family of M-filters to suppression an impulsive noise in biomedical signals (ECG signals). The reference filter is the median filter. PMID- 17271748 TI - Evaluation of different rhythms by hidden Markov models in heart rate variability of hypertrophic cardiomyopathy patients. AB - Synchronization and regularity between different rhythms were evaluated in the HRV using hidden Markov models (HMMs) at very low (VLF), low (LF) and high (HF) frequency bands. Phase synchronization of these rhythms was studied in RR series of hypertrophic cardiomyopathy (HCM) patients during the sleeping period. Two groups of patients were considered in the HCM group: high risk (HR), patients after aborted sudden death (SCD) or that died during follow up, and low risk (LR), patients without SCD. RR time-series were filtered in the following frequency-bands, VLF, LF and HF. The RR phase differences of HF vs. VLF, HF vs. LF and LF vs. VLF were calculated and then the amplitude range partitioned into 8 bins. Finally, these series (O, observations) were modeled using HMM. The models lambda = (A,B,pi) were selected such that P(O/lambda) was locally maximized. Ergodic topology and N = {5,10,15,20} states were considered also for this analysis. Ergodic HMMs with 10 states were found to be sufficient to characterize the HRV rhythms of HR and LR patients. Different synchronization strength was observed studying the phase entropies. However, only the parameters obtained from the HMM were able to differentiate the different groups, with p-value < 0.0005. PMID- 17271749 TI - Complex dynamics of epileptic EEG. AB - Electroencephalogram (EEG) - the recorded representation of electrical activity of the brain contain useful information about the state of the brain. Recent studies indicate that nonlinear methods can extract valuable information from neuronal dynamics. We compare the dynamical properties of EEG signals of healthy subjects with epileptic subjects using nonlinear time series analysis techniques. Chaotic invariants like correlation dimension (D2) , largest Lyapunov exponent (lambda1), Hurst exponent (H) and Kolmogorov entropy (K) are used to characterize the signal. Our study showed clear differences in dynamical properties of brain electrical activity of the normal and epileptic subjects with a confidence level of more than 90%. Furthermore to support this claim fractal dimension (FD) analysis is performed. The results indicate reduction in value of FD for epileptic EEG indicating reduction in system complexity. PMID- 17271750 TI - Nonlinear analysis of EMG signals - a chaotic approach. AB - This paper aims to present a systematic characterisation of the electromyogram (EMG) signal using a nonlinear chaotic approach. EMG signals from 10 muscles in the leg during walking and maximum voluntary contraction (MVC) were obtained and pre-processed using wavelet based denoising techniques. All signals were tested for non-linearity, stationarity and determinism. Chaotic characterization was done by calculating invariants such as correlation dimension (D2), Lyapunov spectrum (lambda1) and Kaplan-Yorke dimension (D(KY)). The EMG signals were non linear and short-term stationary. Determinism and structure was found in the phase-space by studying the recurrence plots. Based on the values of the chaotic invariants, EMG signals were found to exhibit signs of chaotic behaviour with a dimension between 2 and 3 for walking and 3 and 4 for MVC data. PMID- 17271751 TI - An investigation of EEG artifacts elimination using a neural network with non recursive 2nd order volterra filters. AB - The artifacts caused by various factors, EOG (electrooculogram), blink and EMG (electromyogram), in EEG (electroencephalogram) signals increase the difficulty in analyzing them. In addition, EEG signals containing artifacts often cannot be used in analyzing them. So, it is useful and indispensable to eliminate the artifacts from EEG signals. A neural network with non-recursive 2nd order volterra filters is used to eliminate the artifacts from EEG signals. The proposed method is a new approach in respect to slotting a non-recursive 2nd order volterra filter into individual neurons of a neural network. First of all, in order to investigate the usefulness of the proposed method in eliminating the artifacts from EEG signals, we apply it to the artificial EEG signals mat are weakly stationary process. As the result, the artifacts can be eliminated from EEG signals almost exactly using the proposed method, and ft is suggested the proposed method should be useful in eliminating the artifacts from EEG signals. PMID- 17271752 TI - Correlation dimensions of EEG changes during mental tasks. AB - Nonlinear analysis of electroencephalogram (EEG) signals provides a means for studying the dynamical changes in cortical networks related to brain electrical activity. In this study, the correlation dimension (D2) and point correlation dimension (PD2) were used to investigate the quantitative complexity of EEG during cognitive processes. EEGs were recorded in 30 normal subjects under seven conditions: two resting states and five mental activities. Results show that D2 and PD2 are significantly correlated. Compared to D2, PD2 is more sensitive to EEG data and less computationally intensive. PMID- 17271753 TI - Application of the Empirical Mode Decomposition to the analysis of esophageal manometric data in gastroesophageal reflux disease. AB - The Empirical Mode Decomposition (EMD) is a general signal processing method for analyzing nonlinear and non-stationary time series. The central idea of EMD is to decompose a time series into a finite and often small number of intrinsic mode functions (IMFs). An IMF is defined as any function having the number of extrema and the number of zero-crossings equal (or differing at most by one), and also having symmetric envelopes defined by the local minima, and maxima respectively. The decomposition procedure is adaptive, data-driven, therefore, highly efficient The EMD is first described, and its performance is validated by simulations. The EMD is then applied to the analysis of esophageal manometric time series in gastroesophageal reflux disease. The results show that the EMD may prove to be a vital technique for the analysis of esophageal manometric data. PMID- 17271754 TI - Visual evoked potentials estimation by adaptive noise cancellation with neural network-based fuzzy inference system. AB - Visual Evoked potentials (VEPs) are time-varying signals typically buried in relatively large background noise known as the electroencephalogram (EEG). An adaptive noise cancellation with neural-network-based fuzzy inference system was used and the NNFIS was carefully designed to model the VEP signal. An advantage of the method in this paper is that no reference signal is required. The NNFIS based on Takagi and Sugeno's fuzzy model has the advantage of being linear-in parameter, which is able to closely fit any function mapping and can track the dynamic behavior of VEP in a real-time fashion. 4 sets of simulated data indicate that the proposed method is appropriate to estimate VEP. A total of 150 trials are processed to demonstrate the superior performance of the proposed method. PMID- 17271755 TI - Autonomic Information Flow during awakeness, sleep, and multiple organ dysfunction syndrome assessed by mutual information function of heart rate fluctuations. AB - The Autonomic Information Flow (AIF) represents the complex communication within the autonomic nervous system (ANS). It can be assessed by the mutual information function (MIF) of heart rate fluctuations (HRF). AIF represented by HRF is based on several interacting physiological mechanisms operating at different time scales. Therefore one prominent time scale for HRF complexity analysis is not given a priori. MIF reflects the information flow at different time scales. This allows a more specific characterization of the complex communication leading to dynamic stability (homeostasis) of the cardiovascular-respiratory system. Three clinically relevant examples of autonomic communication, namely AIF of normals during awake state and deep sleep, and of patients with multiple organ dysfunction syndrome (MODS) were investigated. In these states MIF clearly represents and distinguishes the different communication in dependence on the time scale of information transfer. The results confirm our systems-theoretical concept that AIF, represented by MIF, characterizes the complex communication of the ANS at different time scales. PMID- 17271756 TI - Image reconstruction for magnetic induction tomography. AB - Image reconstruction in magnetic induction tomography is a non-linear, ill conditioned, inverse problem. Iterative methods provide a means to reconstruct the conductivity distribution. During reconstruction both the forward solution and the Jacobian matrix need to be calculated. In this paper, we reconstruct the electric conductivity distribution using a non-linear regularised Gauss Newton method and based on our knowledge this is the first MIT reconstruction using non linear scheme. PMID- 17271757 TI - An anatomically based mathematical model of the gastroesophageal junction. AB - In this study the construction of an initial three-dimensional anatomically based mathematical model of the esophagus is presented. The aim of this model is to provide a framework with which to examine the functional behavior of the esophagus and the lower esophageal sphincter during swallowing. Anatomical data from the Visible Human Project was used to provide the outlines of the regions of interest. A C/sup 1/ continuous cubic Hermite finite element mesh was then created using an iterative finite element linear fitting process to an RMS error less than 1 mm. Muscular fiber information was embedded within the model using data from published literature. There is a current lack of detailed microstructural data on the gastroesophageal junction. We describe the specialist measurement rig that we propose to use to obtain the microstructural information in our experimental studies. PMID- 17271758 TI - Spatio-temporal frequency characteristics of perceptual filling-in. AB - When a small object surrounded by a dynamic texture is presented in human peripheral vision, the object is perceived to fade and disappear within a few seconds, under certain conditions. This phenomenon is called perceptual filling in. Characteristics of filling-in for various kinds of surrounding textures is important to understand the manner of information processing in human vision, because filling-in has been considered that it greatly contributes to capturing external visual information efficiently. From this point of view, we have proposed a model of the filling-in process to address the phenomenon when a small homogeneous area (filling-in target), which is surrounded by spatio-temporal frequency limited random-dot dynamic textures, is presented to an observer's peripheral vision (Proc. IC-EMBS2003). This study reports measurement of time to filling-in for various surrounding dynamic textures that have different spatio temporal frequency. Applying these results to the proposed model, we estimate the time course of distinguishability of the target from surround (perceptual power). The estimate indicates that if spatial frequency of dynamic textures is low, lower spatio-temporal sensitivity decreases perceptual power more rapidly. However, the opposite property appears if spatial frequency is high. PMID- 17271759 TI - Photon tracking in a multilayer tissue model. AB - A multilayer tissue description was employed in a Monte Carlo simulation of light tissue interaction to study photon travel through skin. Paths of photons returning to the tissue surface at a certain range from the point of entry (emitter-detector spacing) were collected. The simulation demonstrates that highly absorptive discrete layers (e.g., containing melanin or blood) tend to channel photons away. As a result, the dependence of mean depth of photon penetration on wavelength is quite different from the predictions of a homogeneous tissue model. The impact upon our understanding of pulse oximetry is discussed. PMID- 17271760 TI - A modeling paradigm incorporating parametric and non-parametric methods. AB - A novel parametric/non-parametric modeling paradigm was defined and used in characterization of synaptic transmission. In this paradigm, parametric and nonparametric techniques were incorporated in a complementary manner. Non parametric method was used to generalize experimental data and extract system input/output properties. It provided a quantitative and intuitive way to validate a parametric model with respect to general, complete input patterns. Biological processes or mechanisms missed by the conventional parametric modeling approach were revealed and subsequently included into the modified parametric model. PMID- 17271761 TI - Analysis and reliability of posturographic parameters in Parkinson patients at an early stage. AB - Aim of this work was to evaluate Parkinsonian (PARK) patients at their initial stage of the disease by static posturography in order to study: the stability of posture system; the role of visual input; the influence of an acute administration of levodopa. This would allow the creation of a database that can be useful to follow the progression of the disease. Attention was also focused on the assessment of the reliability of quantitative posturographic parameters (PP); a large number of PP that can be derived using classical, structural, and nonlinear approaches have been considered. Particular attention has been given to this latter approach. The class of PD subjects examined in this work resulted to be very different from classical Parkinsonian subjects studied in literature. PMID- 17271762 TI - Age of people and aging problem. AB - To apply technology to problems of age and aging, we need to better understand these problems and to develop operational technique for their solving. Creation of foundations for such a technique by means of a multifaceted model of age is the main goal of this paper. The suggested approach is based on the system theory of time, multilayer model of evaluation, and on differentiation of three functional subsystems in the human organism: biological, physiological, and psychological. PMID- 17271763 TI - Theoretical study of BOLD response to sinusoidal input. AB - This is a theoretical study of a compelling model of blood oxygen level-dependent (BOLD) response dynamics, measured in functional magnetic resonance imaging (fMRI). The novelty of this study involves the way the model is driven sinusoidally, in order to avoid onset and offset transients that pose difficulties in data analysis and interpretation. The driving frequency ranges over the natural time scales of the hemodynamic response (0.01-1 Hz), which also corresponds to the period in typical boxcar stimulus designs. At low stimulus amplitude, the predicted BOLD response is quasi-linear. The amplitude exhibits a mild peak near the modulation frequency 0.1 Hz, and falls rapidly for higher frequencies. The phase lag relative to the stimulus is a monotonically increasing function of the modulation frequency. These findings illustrate the dynamical nature of the BOLD response, and could be used to optimize experimental designs that admit sinusoidal modulation. Higher stimulus amplitude elicits nonlinear behavior characterized by a double peak during the positive deflection of the BOLD response. This finding is particularly interesting, because similar double peaks are seen frequently in BOLD data. PMID- 17271764 TI - A new method for identifying rigid link models of lower limbs. AB - A new method for identifying rigid link models of human lower limbs has been proposed in this paper. The method was motivated by necessity of simulating human body movements for rehabilitation or for design of assistive devices. The method is based on combination of random search and least squares estimation techniques. Simulation and experimental results are given to illustrate the effectiveness of the proposed method. PMID- 17271765 TI - The role of lipid rafts in cell surface BCR antigen binding dynamics. AB - B lymphocyte activation results from the stimulation by large immune complexes involving antigens, antibodies, rafts and complement factors. Cell activation requires co-localization of the interacting molecular components. One of the main elements leading to this localization is the presence on the cell surface of lipid rafts. We show here that an appropriate amount of lipid rafts help to significantly (2- 3 orders of magnitude) raise the sensitivity of B lymphocyte to surrounding high valence antigens. The analysis was done using a newly developed graphically visualized, Monte Carlo (MC) simulation of the cell surface dynamics. Currently this platform represents a feasible, advanced and reliable framework to investigate the cell surface in general. We describe the model and determine, utilizing our model, the effect of lipid rafts surface fraction on the properties of B cell response to immune complexes. We validate our results using an approximate set of ODEs. PMID- 17271766 TI - Optimal time points sampling in pathway modelling. AB - Modelling cellular dynamics based on experimental data is at the heart of system biology. Considerable progress has been made to dynamic pathway modelling as well as the related parameter estimation. However, few of them gives consideration for the issue of optimal sampling time selection for parameter estimation. Time course experiments in molecular biology rarely produce large and accurate data sets and the experiments involved are usually time consuming and expensive. Therefore, to approximate parameters for models with only few available sampling data is of significant practical value. For signal transduction, the sampling intervals are usually not evenly distributed and are based on heuristics. In the paper, we investigate an approach to guide the process of selecting time points in an optimal way to minimize the variance of parameter estimates. In the method, we first formulate the problem to a nonlinear constrained optimization problem by maximum likelihood estimation. We then modify and apply a quantum-inspired evolutionary algorithm, which combines the advantages of both quantum computing and evolutionary computing, to solve the optimization problem. The new algorithm does not suffer from the morass of selecting good initial values and being stuck into local optimum as usually accompanied with the conventional numerical optimization techniques. The simulation results indicate the soundness of the new method. PMID- 17271767 TI - A genetic algorithms' approach to the exploration of parameter space in mesoscopic multicellular tumour spheroid models. AB - The design of accurate in silico cancer models capable of quantitatively predicting tumor growth is an important goal in cancer research today. Mesoscopic models have shown great promise in this scenario; however, their use is often inhibited by the difficulty in correctly assigning parameter values. In this paper, enabled by an extremely computationally efficient mesoscopic model, we propose a generic algorithms' (GAs) approach to the exploration of parameter space. Analysis of the results suggest that this novel application of GAs to tumor growth models both facilitates the attribution of parameter values to the fitting of experimental data and, more importantly, lends insight to the role played by the different parameters in regulating the tumor model growth. PMID- 17271768 TI - Modeling mammary gland morphogenesis as a reaction-diffusion process. AB - Mammary ducts are formed through a process of branching morphogenesis. We present results of experiments using a simulation model of this process, and discuss their implications for understanding mammary duct extension and bifurcation. The model is a cellular automaton approximation of a reaction-diffusion process in which matrix metalloproteinases represent the activator, inhibitors of matrix metalloproteinases represent the inhibitor, and growth factors serve as a substrate. We compare results from the simulation model with those from in-vivo experiments as part of an assessment of whether duct extension and bifurcation during morphogenesis may be a consequence of a reaction-diffusion mechanism mediated by MMPs and TIMPs. PMID- 17271769 TI - A three-dimensional fractal model of tumour vasculature. AB - We constructed a three-dimensional fractal model of the vascular network in a tumour periphery. We model the highly disorganised structure of the neoplastic vasculature by using a high degree of variation in segment properties such as length, diameter and branching angle. The overall appearance of the vascular tree is subjectively similar to that of the disorganised vascular network which encapsulates tumours. The fractal dimension of the model is within the range of clinically measured values. PMID- 17271770 TI - Center of mass function approximation. AB - In this paper, a hybrid genetic algorithm sum-of-sines model is developed to estimate the resultant center of body mass (COM) trajectory. The COM is an important parameter to consider when evaluating or analyzing human postural control, and is indicative of the system's stability. However, currently available systems that calculate the COM are not readily available for clinical routine assessment, making it difficult to widely assess balance problems. The input to the genetic sum-of-sines model developed in this paper is acquired through two accelerometers; equipment that is inexpensive, easy to use and portable. The results indicate that the model developed in this paper shows promising results for obtaining COM estimates that have clinical applications. PMID- 17271772 TI - Hand force estimation using Fast Orthogonal Search. AB - The use of the Fast Orthogonal Search (FOS) method is presented for the estimation of human hand force based on electromyogram (EMG) signal readings and sensed elbow angular position. The use of inexpensive and easily portable EMG electrodes and position sensors would be advantageous in many applications compared to the use of force sensors which are often very expensive and require bulky frames to be used. A single degree-of-freedom robotic experimental testbed has been constructed which allows for data collection, model identification and validation of EMG-force models. FOS identifies the models extremely rapidly with similar or better accuracy compared to existing methods. PMID- 17271771 TI - An agent-based computational approach for representing aspects of in vitro multi cellular tumor spheroid growth. AB - There have been many efforts to explain and simulate tumor growth with mathematical and computational models. However, none have systematically examined the behaviors of tumor spheroids during growth. The interactions among tumor cells during growth are also not well understood. We have implemented an agent based computational approach to study the macro- and micro- behaviors of avascular tumor spheroids during growth. Our simulations of tumor spheroid growth begin with a single tumor cell in optimal environmental conditions. We observe an initial phase of rapid growth, during which the shape of the collective approximates a spheroid. Subsequently a characteristic layered structure develops, consisting of an outermost proliferating cell layer, an intermediate quiescent cell layer, and a central necrotic core. These behaviors of our in silico spheroids map well to experimental in vitro observations. PMID- 17271773 TI - Saccadic parameters for early identification of neuronopathic Gaucher's disease. AB - For a successful treatment of the neurological form of Gaucher's disease ,an early identification is necessary. Often an alteration of the horizontal saccadic eye movements constitutes the first sign of a central nervous system involvement. In order to obtain an early identification of the neuronopathic forms of the disease, often masked by the use of the enzyme replacement therapy, the classical saccadic characteristics (Latency, Amplitude vs. Duration and Amplitude vs. Peak Velocity relationships) are not usable. This work studies if some other parameters (Mean Velocity/Peak Velocity, Kurtosis, Skewness, Asymmetry), are able to describe the saccadic velocity profiles, could be considered to build an expert system able to reach the aim. PMID- 17271774 TI - Systems approach to modeling the neuronal CPG for leech swimming. AB - This paper proposes a mathematical model of the neuronal central pattern generator (CPG) for leech swimming. The model is developed through the "systems approach" where dynamical components and their connections are first identified through input/output data from physiological experiments and then integrated into a chain of nonlinear oscillators. Our approach leads to a model of moderate complexity when compared with existing models developed through biophysical principles. We show through numerical simulations that our model can successfully reproduce the phase coordination observed in the isolated nerve cord of the leech CPG. As a byproduct, a prediction is obtained for the intrinsic period gradient along the nerve cord. PMID- 17271775 TI - Speech enhancement for an artificial larynx using a low-dimensional model of the hearing process. AB - After total laryngectomy the normal voice can be replaced by an electronic artificial larynx (AL). However, the results of the surrogate voice are not overall satisfying due to a robotic clattered sound of that prosthesis. In this paper the results of a sound investigation for an AL are presented. This work is part of our AL research project of laryngectomee's speech enhancement. As a result an autoregressive model of the hearing process is derived that can directly be used for speech enhancement. PMID- 17271776 TI - A binocular pupil model for simulation of relative afferent pupil defect, RAPD. AB - The human pupil is an important element studied in many clinical procedures. The binocular pupil model presented has a topology encompassing much of the complexity of the pupil system neurophysiology. The dynamic parameters of the model were matched against pupil experiments under multiple conditions. It simulates responses to the swinging flashlight test for different degrees of relative afferent pupil defects, RAPD. PMID- 17271777 TI - Synaptic plasticity in neuronal network models can explain patterns of bursting activity seen in temporal lobe epileptic seizures. AB - High-resolution time-frequency analyses of ictal EEG allow for identification and characterization of ictal patterns. These patterns reflect alterations in the brain network synchrony. It is not clear why seizures undergo these dynamical changes and what mechanisms contribute to or cause these changes. In this work we use neural modeling studies to address these issues. We investigate the role of synaptic plasticity and nonsynaptic neuronal plasticity (firing frequency adaptation) in regulating pattern of neuronal network synchrony. We show that nonsynaptic neuronal plasticity (i.e. calcium dependent afterhyperpolarization in neurons) can regulate the frequency of the dominant rhythm in EEG while synaptic potentiation may be responsible for irregular bursting prior to seizure termination. PMID- 17271778 TI - Using system identification to model the transmission of vibroarthrographic signals. AB - Vibroarthrographic signals have been proposed as a noninvasive tool for the diagnosis of joint injury. Models of VAG generation and transmission are required before application of this technique can begin. An experiment has been designed and performed to estimate sound transmission in the human knee at set joint angles. Linear frequency domain models and linear and nonlinear time domain models were estimated from the experimental data. Linear models with high accuracy were identified for knees at an angle of 90/ degrees . Models identified from angles below 90 degrees had relatively low accuracy. PMID- 17271779 TI - Modeling HIV-1 dynamics and the effects of decreasing activated infected T-cell count by filtration. AB - Over the past 10 years mathematical models have been developed using differential equations for the progression of HIV-1 to AIDS in an infected patient. Additional terms and formulations are presented over time, as the disease is better understood. Experimentation has been used to obtain many of the modeling parameters. These previous works focus primarily on modeling the progression of the disease, some with intervention such as HAART drugs. Attempts have been made to filter HIV-1 and HIV-1-infected T-cells from the blood. A model is developed that characterizes the rate of filtrations impact on disease progression. Such studies could be also used to investigate the impact of an implantable HIV-1 filter. Proliferation rates of actively and latently infected T-cells are significant and have been incorporated into the models developed in this paper. PMID- 17271780 TI - 1D and 3D models of auto-regulated cerebrovascular flow. AB - The Circle of Willis (CoW) is a ring-like structure blood vessels at the base of the brain that distributes arterial blood to the cerebral mass. 1D and 3D CFD models of the Circle of Willis have been created to simulate clinical scenarios such as inclusions in afferent arteries and absent circulus vessels. Both models capture cerebral haemodynamic auto-regulation using proportional-integral controller to modify efferent artery distances to maintain optimal efferent flowrates for a given cycle geometry and afferent blood pressure. The models can be used to identify at-risk cerebral arterial geometries and conditions prior to surgery or other clinical procedures. The model is particularly relevant in this instance, with its fast execution time suitable for real-time clinical decisions and senario testing, as long as it captures the necessary details as a model would. Results show excellent correlation between models for the transient efferent flux profile with differences more than 5%. The assumption of strictly Poiseulile flow in the model allows more flow through the geometrically extreme communicating arteries than the 3D model. This discrepancy is overcome by increasing the resistance to flow in the ACoA the 1D model to better match the resistance seen in the 3D model, significantly improving correlation of the results. PMID- 17271781 TI - Dynamics of cryopreserved human carotid arteries. AB - The viscoelastic properties of the arterial wall are responsible for their functional role in the arterial system. Cryopreservation is widely used to preserve blood vessels for vascular reconstruction but is controversially suspected to affect the dynamic behaviour of these allografts. The aim of this study was to determine whether differences in the dynamic behaviour exist or not between fresh and cryopreserved human common carotid arteries (CCA). Using a previously developed mock circulation system, dynamic pressure-diameter tests were performed on segments of human fresh (n=10) and cryopreserved arteries (n=7). A diameter-pressure transfer function was designed to evaluate the wall dynamics. An adaptive model was fit to obtain its frequency response. Three models were tested. Results show that non-significant differences exist between wall dynamics of fresh and cryopreserved segments of human CCA. PMID- 17271782 TI - Kalman filter modeling of cerebral blood flow autoregulation. AB - A parameter estimation scheme for dynamic systems is employed to simultaneously estimate the states and parameters of the model of human cerebral blood flow velocity as a function of mean arterial blood pressure. The estimation results show 20-40% reduction in the output mean square error compared to that of the one obtained from the computer model addressed in [1]. The estimation scheme estimates the parameters and states of the system, as well as the level of the observed and process noise variances. This approach is more extensive than the one that was applied to the same system in the previous work [2], in which only the Kalman filter was applied and the system was restricted to some specific constraints. PMID- 17271783 TI - Continuous noninvasive blood pressure measurement by pulse transit time. AB - Blood pressure measurement is performed either invasively by an intra arterial catheter or noninvasively by cuff sphygmomanometry. The invasive method is continuous and accurate but has increased risk; the cuff is safe but less reliable and infrequent. A reliable continuous noninvasive blood pressure measurement is highly desirable. While the possibility of using pulse transit time to monitor blood pressure has previously been investigated, most studies were limited to calculating the correlation of the pulse transit time and blood pressure under rather static conditions. The relationship between the pulse transit time and blood pressure is yet to be clearly identified. This paper focuses on the modeling between the two values and presents results on cases where dramatic variation in blood pressure of the patient was induced by drug administration or surgical stimulation. PMID- 17271784 TI - Parametric differential approach for modeling the upper limb human vasculature. AB - A parametric approach is proposed for the characterization of the upper vascular tree. The novelty of the approach resides in it being differential: the processed signals are the photoplethysmograms obtained non-invasively from the left and right indexes. The investigated model is an ARX (auto-regressive with exogenous input) where the order has been estimated utilizing standard techniques. The model coefficients show a relatively high degree of stability. PMID- 17271785 TI - Calibrating an intracranial pressure dynamics model with clinical data - a progress report. AB - We describe the calibration of a computer model of intracranial pressure (ICP) dynamics to correspond with annotated clinical data taken from a patient being treated for elevated ICP due to a traumatic brain injury. The research protocol employed during treatment includes adjusting the elevation of the head of the bed, adjusting the ventilator settings to induce mild hyperventilation and hypoventilation, and adjusting the height of the cerebrospinal fluid drainage system. The model behavior corresponds to the experimental data quite well in the case of the changing the head of the bed, but less well in the case of changing the ventilator settings. PMID- 17271786 TI - A blood glucose prediction system by chaos approach. AB - For suppressing the development of diabetes mellitus and the onset of complications, an insulin therapy has been used for suppressing and normalizing the change of a blood glucose. In a blood glucose control by linear method such as conventional ARMA, however, there exists problem that results in the frequency of hypoglycemia. In a blood glucose prediction by a chaos theory, there also exists problem that results in the lower accuracy on behalf of the impossibility in the long-time prediction. For the improvement in the prediction accuracy of the blood glucose that looks like complicated time series, we propose a system combining the deterministic chaos theory using equal time interval, local fuzzy reconstruction method, and minimal linear model. By local fuzzy reconstruction method, we can predict the fasting blood glucose in the short term and then we can estimate the appropriate amount of insulin shot based on the measured bedtime blood glucose. Using the system, the change of blood glucose can be suppressed and normalized and the number of the insulin dosage a day can be reduced to once. Here we report the high effective result of applying the system to type II diabetes mellitus patient. PMID- 17271787 TI - Consideration of physical condition in estimation of blood glucose via data mining. AB - Many diabetics carry a portable-type blood glucose monitor and collect their own blood to examine their blood glucose levels daily (self monitoring of blood glucose, SMBG). The use of a physical condition variable was suggested in order to estimate the blood glucose level for diabetics. Four sets of data, including FBG, food intake, metabolic rate and physical condition, were collected from four Type 1 diabetics over a five-month period. Using these data, an increasing or decreasing tendency for FBG for the next day was estimated using the data mining method. The results revealed that the estimation accuracy was improved when a physical condition variable was used. An average correspondence rate of 81 % was observed, with a maximum of 90 %. These results indicated that the data mining method could be effective in the estimation of blood glucose levels. PMID- 17271788 TI - Long term verification of glucose-insulin regulatory system model dynamics. AB - Hyperglycaemia in critically ill patients increases the risk of further complications and mortality. A long-term verification of a model that captures the essential glucose- and insulin-kinetics is presented, using retrospective data gathered in an intensive care unit (ICU). The model uses only two patient specific parameters, for glucose clearance and insulin sensitivity. The optimization of these parameters is accomplished through a novel integration based fitting approach, and a piecewise linearization of the parameters. This approach reduces the non-linear, non-convex optimization problem to a simple linear equation system. The method was tested on long-term blood glucose recordings from 17 ICU patients, resulting in an average error of 7%, which is in the range of the sensor error. One-hour predictions of blood glucose data proved acceptable with an error range between 711%. These results verify the model's ability to capture long-term observed glucose-insulin dynamics in hyperglycaemic ICU patients. PMID- 17271789 TI - Optimal glucose-insulin control in H2 space. AB - In this case study optimal glucose-insulin control in the Hardy H/sub 2/-space is presented for diabetic patients under intensive care. The analysis is based on a modified two-compartment model. First the classical LQ optimal control design method is considered, and then its extension the so called disturbance rejection LQR (LQ rejection) method, based on the MINIMAX differential game is applied to control design. To demonstrate the results of these two methods, the simulation of the dynamical performance of the non-linear closed loop system in case of food (sugar) intake has been carried out. For the symbolic and numeric computations Mathematica and Matlab-Simulink are used. PMID- 17271790 TI - A pulse-step model of accommodation dynamics. AB - Abrupt step changes in human ocular accommodation have been traditionally modeled using a continuous feedback control system supplied by a step-position control signal. However, recent behavioral data show that, while the velocity of the step response increases proportionally with response magnitude, the peak acceleration remains constant. This argues against a step input control signal and suggests the existence of a dual-mode control of accommodation: an initial fixed innervation component related to the constant acceleration followed by an innervation component that increases with response amplitude. Specifically, we proposed a pulse-step that provides a velocity-coded input to the system that is integrated to form two position-input signals, that when combined produce high velocity responses. The pulse height controls the acceleration; the pulse width controls the velocity and the step height controls the position of the accommodation response. The pulse-step model simulations were similar to empirical observations and illustrated an enhancement of the peak velocity of accommodation when compared to when the pulse component was removed from the model. The main functional advantage of the pulse is to overcome the high viscosity of the crystalline lens and achieve rapid step responses. PMID- 17271791 TI - Representing intestinal drug transport in silico: an agent-oriented approach. AB - A prototype Epithelio-Mimetic Device (EMD) was developed and tested. EMD components are designed to map logically to biological components at multiple levels of resolution. Those components are engineered to represent actual components within an in vitro cellular system used to study intestinal drug transport. Our goal is that the behaviors of the EMD closely match observed behaviors of the in vitro systems for a wide variety of drugs. Early stage system verification is achieved. The general patterns of experimental results from the EMD for a set of hypothetical drugs having a variety of physicochemical properties reasonably match observed patterns for a wide range of experimental conditions. PMID- 17271792 TI - Physiologically-based minimal model of agitation-sedation dynamics. AB - Agitation-sedation cycling in critically ill patients, characterized by oscillations between states of agitation and over-sedation, damages patient health and increases length of stay and cost. The model presented captures the essential dynamics of the agitation-sedation system, is physiologically representative, and is validated by accurately simulating patient response for 37 critical care patients. The model provides a platform to develop and test controllers that offer the potential of improved agitation management. PMID- 17271794 TI - A new biphasic minimal model. AB - Plasma insulin levels vary in an oscillatory fashion in both basal and postprandial states. The basic pattern is one of rapid (10 min) pulses superimposed on slower (50-100 min) oscillations. These oscillations increase after a glucose load and are altered in type 2 diabetes, impaired glucose tolerance or ageing. In response to a square-wave increase in interstitial glucose, beta-cells release insulin in a biphasic manner, with a sharp first phase lasting approximately 10 min followed by a gradually increasing release (second phase). Both phases are important for maintaining glucose homeostasis, but more emphasis has been placed on early insulin release because its attenuation causes glucose intolerance and late hyperinsulinemia. A new minimal model of glucose and insulin concentrations in plasma, which incorporates both the pulsatile and biphasic aspect of insulin production into existing minimal models, has been developed. The model is founded upon recent results on the action of beta-cells as fuel sensors and the dynamics of secretory granule exocytosis. The inclusion of a flexible model of insulin release is essential if the model is to be used to describe diabetic patients for more than a few hours and is a step towards a 24 hour free living model. PMID- 17271793 TI - Estimation of ethanol infusion profile to produce specified BrAC time course using physiologically-based pharmacokinetic (PBPK) models. AB - A procedure for estimating the alcohol infusion profile required to produce a specific breath alcohol concentration (BrAC) time course using a PBPK model is described. Model parameter values are predicted from linear relationships to readily measurable physical characteristics or morphometrics. An algorithm to optimize this transformation, based upon recorded clinical experimental data, is provided. A substantial improvement in all error statistics, in relation to the original transform was obtained. PMID- 17271795 TI - Quantifying uncertainty bounds in anesthetic PKPD models. AB - A major challenge faced when designing controllers to automate anesthetic drug delivery is the large variability that exists between and within patients. This intra- and inter-patient variability have been reported to lead to instability. Hence, defining and quantifying uncertainty bounds provides a mean to validate the control design, ensure its stability and assess performance. In this work, the intra- and inter-patient variability measured from thiopental induction data is used to define uncertainty bounds. It is shown that these bounds can be reduced by up to 40% when using a patient-specific model as compared to a population-normed model. It is also shown that identifying only the overall static gain of the patient system already decreases significantly this uncertainty. PMID- 17271796 TI - Real-time theoretical compartmental model of blood-brain barrier drug delivery. AB - This study developed upon the Mahar Doan and Boje simulations to create a novel pharmacokinetic/pharmacodynamic real-time compartmental model in Simulink. The model allowed for varying combinations of oral and intravenous drug dosing under steady and nonsteady-state endogenous transport inhibition methods. A joint pharmacodynamic model simulated an extracellular receptor binding process and an intracellular enzymatic process as drug effect sites. Initial simulations were compared with the Mahar Doan and Boje data. Further simulation demonstrated the freedom and broadened understanding of drug kinetics and dynamics the implemented real-time model provided. PMID- 17271797 TI - Enhancing parameter precision and the minimal modeling approach in type I diabetes. AB - An evaluation of a simple model including external perturbations was evaluated for its usefulness in predicting diabetic patients' behavior. The model proposed has been derived from Cobelli and Marl's comprehensive model and is structurally identifiable. The optimization was carried out on data gathered using CGMS (Medtronic MiniMed) on 3 subjects. The model was also optimized after performing a model-based signal enhancement. The results obtained before and after signal enhancement showed a promising reduction in the variation coefficient of the estimated parameters. This reduction is expected to be useful in the design of a closed loop controller for subcutaneous insulin delivery. PMID- 17271798 TI - Estimation of ECG signal of closely separated bipolar electrodes using thorax models. AB - New miniaturized portable ECG measuring devices may require reduced electrode size and distance. Modeling tools can be useful in predicting the behavior of electric field between electrodes. This work introduces a project where the effect of interelectrode distance (IED) of ECG precordial electrodes was studied with a model of the thorax as a volume conductor and with body surface potential map (BSPM) data. The objective was to study how the IED affects the signal strength and how well the modeling data corresponds to the clinical data. 2D and 3D finite difference method (FDM) torso models based on visible human man data were used. On these FDM models, the electrodes9 sensitivity to measure the electric field of the heart was derived. The results were compared to clinical 120 channel BSPM data. It was found out that reducing the IED obviously decreases the signal strength. According to the clinical data, the magnitude of this effect depends on the electrode location. This study indicates that modeling the volume conductor can predict the signal strength obtained with given electrode configurations. 3D modeling is more accurate in predicting the signal strength from clinical recordings; however, also simple and fast 2D modeling results show comparable values. PMID- 17271799 TI - Parametric sensibility study of the sinoatrial node math model. AB - The results of the parametric sensibility study to the sinoatrial node math model was presented. The model was proposed by H. Zhang, A. V. Holden and M.R. Boyett. The sensitivity analysis indicates that the sodium and potassium ionic concentrations need to be controlled in order to maintain the normal behavior of the node. The calcium concentrations changes simulated don't produce significant effects over the operation of the node. One response surface model was developed as a simplification of original model. The diastolic depolarization rate was redefined in order to allow its measure in potential waves for peripheral node cells. PMID- 17271800 TI - Prediction of implantable ECG lead systems by using thorax models. AB - New implantable ECG devices may provide more stable and noiseless measurements compared to body surface ECG measurements. When the electrodes are moved to inside of the body the way the ECG measurement is done is changing. Modeling can be an effective way to study effects of implantation to the capacity of electrodes to measure ECG compared to surface measurements. This work introduces a project where effects of electrode implantation to the magnitude and direction of lead sensitivity to detect cardiac source, lead field, was studied with a model of the thorax as a volume conductor. The study was based on 3D finite difference method (FDM) featuring visible human man. The results of the study indicate that the effect of electrode implantation under the skin (5-15 mm) to the way they measure ECG is rather small. Magnitude change is dependent of the studied lead and the change of the sensitivity to heart's equivalent sources in direction of lead field is minor. PMID- 17271801 TI - Identification of patient specific parameters for a minimal cardiac model. AB - A minimal cardiac model has been developed which accurately captures the essential dynamics of the cardiovascular system (CVS). This paper develops an integral based parameter identification method for fast and accurate identification of patient specific parameters for this minimal model. The integral method is implemented using a single chamber model to prove the concept, and turns a previously nonlinear and nonconvex optimization problem into a linear and convex problem. The method can be readily extended to the full minimal cardiac model and enables rapid identification of model parameters to match a particular patient condition in clinical real time (3-5 minutes). This information can then be used to assist medical staff in understanding, diagnosis and treatment selection. PMID- 17271802 TI - Simulation of atrial electrophysiology and body surface potentials for normal and abnormal rhythm. AB - The effect of different atrial electrical activation sequences (sinus rhythm and atrial flutter circling in the right atrium) on the body surface potentials is investigated in this study. A realistic volume conductor model consisting of atria, lungs, chest and blood masses is generated from image stacks recorded by magnetic resonance imaging. The electrical sources-the transmembrane potentials within the atrial volumetric model are simulated for different atrial rhythms employing a cellular automaton capable of considering different parameters depending on the specific properties of the tissues. The potentials on the torso surface are computed applying the finite element method for solving the differential equations derived from the bidomain theory. Both the simulated atrial activation patterns and the computed torso potentials for atrial sinus rhythm and atrial flutter are in qualitatively and quantitatively good agreement with data measured in humans. The simulation of body surface potentials generated by different electrical activation sequences in the atria or ventricles allows testing and assessing noninvasive imaging of cardiac electrophysiology, as both the potentials on the body surface and the reference activation in the heart are available. PMID- 17271803 TI - A software framework for solving problems of bioelectricity applying high-order finite elements. AB - Electrical activity in biological media can be described in a mathematical way, which is applicable to computer-based simulation. Biophysically mathematical descriptions provide important insights into the electrical and electrophysiological properties of cells, tissues, and organs. Examples of these descriptions are Maxwell's and Poisson's equations for electromagnetic and electric fields. Commonly, numerical techniques are applied to calculate electrical fields, e.g. the finite element method. Finite elements can be classified on the order of the underlying Interpolation. High-order finite elements provide enhanced geometric flexibility and can increase the accuracy of a solution. The aim of this work is the design of a framework for describing and solving high-order finite elements in the SCIRun/BioPSE software system, which allows geometric modeling, simulation, and visualization for solving bioelectric field problems. Currently, only low-order elements are supported. Our design for high-order elements concerns interpolation of geometry and physical fields. The design is illustrated by an implementation of one-dimensional elements with cubic interpolation of geometry and field variables. PMID- 17271804 TI - Influence of EEG measurement montage on source localization error bounds due to head modeling errors caused by brain lesions. AB - EEG source reconstruction accuracy depends on numerous factors, including head modeling accuracy, the specific inverse approach and the adopted EEG measurement montage. In This work we present results of a simulation study, performed with an eccentric-spheres head model, investigating the EEC dipole source reconstruction errors bounds caused by neglecting brain lesions in the head model. To separate the effect of head modeling accuracy from errors due to specific inverse approach, we based our study on an exhaustive "goal function (GF) scan" method, in which the source parameter search space is discretized and at every scan point a GF value is computed, allowing the exhaustive determination of dipole source reconstruction error bounds and the confidence interval for inverse problem solution. Six different electrodes montages have been considered, from a minimum of 32 to a maximum of 128 electrodes, keeping spatial sampling constant; electrodes coverage increases varying minimum electrodes latitude on the scalp. Source localization and intensity error bounds obtained justify the conclusion that, in the presence of a lesion, a pathological head model must be selected to accurately reconstruct the neural source, as the systematic error due to neglecting lesion progressively increases adopting smaller EEG electrodes coverages. PMID- 17271805 TI - Multiple current dipole estimation in a realistic head model using R-MUSIC. AB - Neural activity in the human brain can be modeled as a volume conductor with current dipoles representing collections of neuronal sources. Determining the spatio-temporal characteristics of the sources from such models requires a solution to the inverse electrostatic problem. In this study, the Recursive MUSIC algorithm was used to invert combinations of synchronous and asynchronous dipolar sources in an anatomically realistic head model. The performance was analyzed at signal-to-noise ratios from 0 to 30 dB. Localization of independent sources was excellent, even at low signal-to-noise ratios, demonstrating the potential performance advantages of a spatio-temporal analysis over a purely spatial treatment. Localization for synchronous sources was substantially degraded at signal-to-noise ratios below 20 dB, demonstrating a need for improved methods to distinguish between asynchronous and synchronous sources. PMID- 17271806 TI - Referenced EEG and head volume conductor model: geometry and parametrical setting. AB - Brain electrical activity effects spread (spatially) over the whole head volume conductor. Electric scalp potentials (EEG) are the measurable evidences of such activity. EEG forward problem solution involves computing the scalp potentials at a finite set of sensor locations for a source configuration in a specified volume conductor model of the head or of part of it (reduced model). The use of reduced models is appealing for computational reasons. The skull could be, according to its conductivity, the natural bound for bioelectrical currents flow. However there are huge uncertainties on actual skull conductivity (i.e., 1/80 or 1/15 of brain conductivity). We show here the limits besides which model reduction is possible preserving EEG simulation accuracy according to the two competitive definitions for skull conductivity. The identified limits involve a proper choice for the EEG reference (Cz) as well as dipole equivalent source characteristics (position and orientation). To this end we adopted realistic test head models extended to different percentages of two reference models (extended to the chin) which differ for skull conductivity set either to 1/80 or 1/15 of brain conductivity. PMID- 17271807 TI - A possible mechanism explaining variation in membrane permeability under exposure to weak magnetic fields. AB - The problem of the interaction between electromagnetic fields and a biological system can be properly faced at cell membrane level. Specifically, in this work, the target of the interaction has been located in the charged lipid group emerging from the membrane surface. A possible mechanism based on the Larmor precession theory is here proposed. The results evidence the possibility of specific exposure conditions that enhance the membrane permeability. PMID- 17271808 TI - Identification of a switching model of calcium cycling in isolated rat hearts. AB - So far, the processes involved in regulation of intracellular calcium (Ca/sub i//sup 2+/) in cardiomyocytes have been mainly studied through biochemical and isolated cell analysis. Here, we present a novel technique to model and identify cardiac Ca/sub i//sup 2+/-cycling under physiologically relevant conditions in the intact beating heart. Ca/sub i//sup 2+/ was measured using fluorescence techniques in ex vivo perfused rat hearts. For analysis, we developed a parametric mathematical model, switching between active and inactive calcium release. The kinetic parameters of the two submodes of the model were computed using a recently developed technique from hybrid system identification. Application of the method to control and isoproterenol-stimulated hearts resulted in parameter values within a physiologically reliable range. PMID- 17271809 TI - Modeling transport kinetics with StarLogo. AB - StarLogo, an agent-based modeling and simulation platform, was used to simulate adsorption-mediated transcytosis of a molecule from the lumen side of a cell membrane to the abluminal extra-cellular fluid (ECF). The model contains small nondiffusible substrate molecules, transporters, and substrate-transporter agents. The "reaction" is a transporter combining with the substrate which then crosses the cell cytoplasm. The substrate that is deposited on the ECF side becomes the "product". Results showed characteristics consistent with Michaelis Menten enzyme kinetics. The model can serve as an example of agent-based modeling and simulation. PMID- 17271810 TI - Backscattered ultrasound from contrast microbubbles: effects of tissue and bubble interaction. AB - The propagation of diagnostic ultrasonic imaging pulses in tissue and their interaction with contrast microbubbles is a complex physical process. Our model driven approach is used to gain better knowledge of the different processes involved in the generation of the backscattered contrast echo. It can be divided into three separable stages: linear and nonlinear wave propagation in tissue, the resulting echo from the pulse interaction with the contrast microbubble, and the propagation of the scattered echo. A simplified approach of field simulation is chosen due to the complexity of the task and necessity to estimate comparative contributions of each component of the process. A modified method for spatial superposition of attenuated waves was further developed to enable simulations of low intensity pulse fields in nonlinear attenuating and liquid-like biological medium using weakly focused transducers. Simulations of the acoustic bubble response are carried out with Rayleigh-Plesset equation with the addition of the radiation damping. Theoretical simulations show that contrast bubbles interaction with excitation pulses is the main cause of nonlinear distortions, and a 2-3 dB increase of second harmonic amplitude depends on nonlinear distortions of incident pulse. PMID- 17271811 TI - In silico representation of the liver-connecting function to anatomy, physiology and heterogeneous microenvironments. AB - We have built a collection of flexible, hepatomimetic, in silico components. Some are agent-based. We assemble them into devices that mimic aspects of anatomic structures and the behaviors of hepatic lobules (the primary functional unit of the liver) along with aspects of liver function. We validate against outflow profiles for sucrose administered as a bolus to isolated, perfused rat livers (IPRLs). Acceptable in silico profiles are experimentally indistinguishable from those of the in situ referent based on similarity measure values. The behavior of these devices is expected to cover expanding portions of the behavior space of real livers and their components. These in silico livers will provide powerful tools for understanding how the liver functions in normal and diseased states, at multiple levels of organization. PMID- 17271812 TI - Nonlinear analyses of cell proliferation in the central nervous system reveal stochastic and deterministic components. AB - This paper analyzes the dynamics of cell proliferation in the developing central nervous system. Three different algorithms, Fano factor, Allan factor and detrended fluctuations analysis, are used to estimate de scaling exponent of space numerical series obtained by recording the number and position of proliferating cells along the cephalic-caudal axis of the system. It can be concluded that the dynamics of proliferation involves two component: (a) a random noncorrelated stochastic component representing a basal proliferating activity uniformly distributed along the cephalic-caudal axis and (b) a deterministic nonstationary component that imposes a defined global trend to the process. The deterministic nonstationary trend can be interpreted as the effect of a controlling influence operating along the cephalic-caudal axis. This result indicates that the proliferative activity is spatially organized along the cephalic-caudal axis of the system. PMID- 17271813 TI - Dynamic models of ARDS lung mechanics for optimal patient ventilation. AB - Mechanical ventilation is often used to treat patients with acute respiratory distress syndrome (ARDS). However, the optimal setting is still controversial, and physicians often rely on experience and intuition. The purpose of this research is to develop a model of the essential lung mechanics to help determining the optimal ventilator setting in clinical situations. The model is a compilation of physiologically based mechanics parameters, which are adjustable to represent patient specific conditions. Further investigation improvements are required, however it shows good initial for eventual clinical use. PMID- 17271815 TI - Detection and segmentation of changes of dynamics in biological time series. AB - A method to identify switching dynamics in time series, based on annealed competition of experts algorithm (ACE), has been developed by J. Kohlmorgen, et al (2000). Incorrect selection of embedding dimension and time delay of the signal significantly affect the performance of the ACE method, however. We utilize systematic approaches based on mutual information and false nearest neighbor to determine appropriate embedding dimension and time delay. Moreover, we obtained further improvements to the original ACE method by incorporating a phase space closeness measure during the training procedure as well as deterministic annealing approach. Using these ameliorated implementations, we have enhanced the performance of the ACE algorithm in determining the location of the switching of dynamic modes in time series. The application of the improved ACE method to RR interval data obtained from rats during control and administration of double autonomic blockade conditions indicate that the improved ACE algorithm is able to segment dynamic mode changes with pinpoint accuracy and that its performance is far superior to the original ACE algorithm. PMID- 17271814 TI - Radial basis function neural networks versus fuzzy models to predict return of consciousness after general anesthesia. AB - This work presents two modelling techniques to predict return of consciousness (ROC) after general anaesthesia, considering the effect concentration of the anaesthetic drug at awakening. First, several clinical variables were statistically analysed to determine their correlation with the awakening concentration. The anaesthetic and the analgesic mean dose during surgery, and the age of the patient, proved to have significantly high correlation coefficients. Variables like the mean bispectral index value during surgery, duration of surgery did not present a statistical relation with ROC. Radial basis function (RBF) neural networks were trained relating different sets of clinical values with the anaesthetic drug effect concentration at awakening. Secondly, fuzzy models were built using an adaptive network-based fuzzy inference system (ANFIS) also relating different sets of variables. Clinical data was used to train and test the models. The fuzzy models and RBF neural networks proved to have good prediction properties and balanced results. PMID- 17271816 TI - Relationship between surface temperature distribution and internal heat source size of the in-vitro tissue. AB - ln this paper, the relationship between surface temperature distribution and internal heat source size of the in-vitro tissue was discussed. The method of obtaining internal heat source information from surface temperature distribution will promote the application of thermography. Through approximation, the relationship between surface temperature distribution and internal beat source size of the in-vitro tissue was induced. The reasonability of the approximation was validated by the high match degree between the template generated by the approximation solution and the practical surface temperature distribution. PMID- 17271817 TI - ECG synthesis based on morphing. AB - This work presents a technique for synthesizing realistic electrocardiogram (ECG) signals by morphing two different real ECG signals. The two parent signals are interpolated using spline approximation and then over-sampled. The characteristic feature points are extracted manually from the signals and they are partitioned into component curves between the feature points. The component curves are sampled to obtain the same number of data points for each curve and the feature points are matched. One-dimensional morphing is performed to generate intermediate signals. The intermediate signals are constrained within the physiological bounds of the two real ECG signals. The realistic ECG synthesized could find application for testing an ECG-based biometric identification system and for evaluating ECG signal processing algorithms. PMID- 17271818 TI - Detection of hypervolemia with embedded systems. AB - This work presents methods of biomedical signal processing and interpretation to detect hypervolemia as a cause for oxygen delivery disturbances. A model of the disease patterns for this respiratory disorder is derived and implemented on an embedded system. The model is designed in stateflow and simulated with Matlab using a database of intensive care unit patients to proved inputs for verification. The implementation is done over a wireless micro controller network. PMID- 17271819 TI - Mechanical vasoconstriction for a cerebral myogenic autoregulatory model. AB - This work presents the design of a mechanical vasoconstriction mechanism with application for cerebral autoregulation. The relationship between the applied voltage of a DC motor and the tension within a pressurized vessel wall was utilized for constricting an arteriole segment within an intracranial vascular model. Using current proportional to the string tension, options for closed loop feedback control are considered. PMID- 17271820 TI - An anatomically based model of small intestine excitation. AB - Electrical and magnetic fields are generated by the smooth muscle's electrical activity in the walls of the gastrointestinal system. These fields can be measured on the torso surface. We present a computational model that is capable of simulating the electrical activity occurring within the small intestine. Finite elements were used to represent the geometry of the small intestine. A finer resolution finite difference mesh was defined within this geometrical mesh and used to solve the equations governing the activation of the intestinal smooth muscle. Initial simulations were performed to illustrate the spread of potential along the small intestine. With further development this model will provide a basis for understanding and interpreting noninvasive magnetic measurements from intestinal smooth muscle. PMID- 17271821 TI - Modeling obsessive compulsive disorder. AB - A preliminary computational model for obsessive compulsive disorder is developed using neuro-circuitry information and systems biology principles. The model captures the salient features of the neuro-psychiatric disorder reported in the literature. Studies are on-going to model in more detail both the intra-cellular and extra-cellular features of the model, within the framework proposed. PMID- 17271822 TI - Computational modeling of hysterical paralysis. AB - A preliminary computational model for hysterical paralysis is developed using neuro-circuitry information and systems biology principles. The model captures the salient features of the neuro-psychiatric disorder reported in the literature. Studies are on-going to model in more detail both the intra-cellular and extra-cellular features of the model, within the framework proposed. PMID- 17271823 TI - Motion analysis of right ventricular wall based on an electromechanical biventricular model. AB - Based on our previously developed electrical heart model, an electromechanical biventricular model, which couples the electrical property and mechanical property of the heart, was constructed and the right ventricular wall motion and deformation was simulated using this model. The model was developed on the basis of composite material theory and finite element method. The excitation propagation was simulated by electrical heart model, and the resultant active forces were used to study the ventricular wall motion during systole. The simulation results show that: (1) The right ventricular free wall moves towards the septum, and at the same time, the base and middle of free wall move towards the apex, which reduce the volume of right ventricle; (2) The minimum principle strain (E3) is largest at the apex, then at the middle of free wall, and its direction is in the approximate direction of epicardial muscle fibers. These results are in good accordance with solutions obtained from MR tagging images. It suggests that such electromechanical biventricular model can be used to assess the mechanical function of two ventricles. PMID- 17271824 TI - A sampling multichannel bioimpedance analyzer for tissue monitoring. AB - The paper focuses on principles of designing of a multichannel bioimpedance analyzer based on simultaneous multisine measurement. The measurement task arises due to the need to monitor patients during and after heart surgery operation performing MIMO (multiple-input-multiple-output) bioimpedance measurement. Frequencies of the simultaneously applied sinusoidal excitations must be close but simultaneously varied in a larger range (e.g. from 1 kHz up to 10 MHz). The main idea of the proposed approach is that the use of a rather specific signal system (frequencies of sinusoidal excitations are related as integers and sampling frequencies are properly related/adapted to them) makes it possible to separate responses to different excitations from the measured summary signals by means of a quite simple filter and different (under) sampling rates. PMID- 17271825 TI - Continuous measurement of BRSI in chronic fatigue syndrome. AB - This paper discusses the development of a system to measure continuous cardiac baroreceptor measurement during a 45-minute 70-degree head-up tilt (HUT) of five groups of subjects suffering the following: chronic fatigue syndrome (CFS), CFS with fibromyalgia (CFS-FM), CFS with postural orthostatic tachycardia syndrome (CFS-POTS), controls with POTS (CON-POTS), and controls (CON). The duration of the test was 56-minutes, which included a five-minute supine baseline, a 45 minute HUT and a six-minute recovery period. The system was developed in LabView, and can provide a comparative time analyses of weighted BRSI averages. Baroreflex effectiveness index (BEI) was also investigated over the course of lags 0, 1 and 2 as well as an assessment of overall BEI performance between groups. PMID- 17271827 TI - Estimation of cardiac output from peripheral pressure waveforms using Laguerre model blind system identification. AB - We have developed a new technique, which may enable a more accurate, complete characterization of the circulatory system, including local or global hydrodynamic phenomena, using multiple measurements from several anatomic locations and/or multiple modalities. This technique, Laguerre model blind system identification (LMBSI), uses a Laguerre function series expansion to provide a compact but complete quantitative description of the distinct behavior of two or more circulatory waveforms. LMBSI identifies a set of five parameters per channel plus one common parameter that can be treated as a feature vector and used to predict cardiovascular parameters of interest. Standard statistical techniques can be used to extract information from that compact feature vector. In this paper, multiparameter regression is used to predict cardiac output, using two separate arterial pressure waveforms and the LMBSI algorithm. This serves as a proof-of-principle that two distinct circulatory waveforms, with LMBSI, can be used to characterize the circulatory system. In the future, this technique might be applied to noninvasive circulatory measurements. PMID- 17271826 TI - Removal of eye blinking artifacts from EEG incorporating a new constrained BSS algorithm. AB - A robust constrained blind source separation algorithm (CBSS) has been developed here for an effective removal of eye muscle artifacts from electroencephalograms (EEG). Presently, clinicians reject a data segment if the patient blinked or spoke. The rejected data segment may contain important information that may be masked by the artifact. In the CBSS technique we exploit a reference signals as a constraint. The constrained problem is then converted to an unconstrained problem by means of nonlinear penalty functions weighted by the penalty terms. This leads to the modification of the overall cost function, based on the natural gradient algorithm (NGA), by incorporating a reference signal. PMID- 17271828 TI - Detection of one lung intubation by monitoring lungs sounds. AB - Analysis of lungs sounds for monitoring and diagnosis of pulmonary function is well known. One of the applications of this method is detection of one lung intubation (OLI) during anesthesia or intensive care. An algorithm for detection the one-lung ventilation situation from the lungs sounds is presented. The algorithm assumes a MIMO (Multiple Input Multiple Output) system, in which a multidimensional AR (Auto-Regressive) model relates the input (lungs) and the output (recorded sounds). The unknown AR parameters are estimated, and a detector based on the estimated eigenvalues of the source covariance matrix is developed, in order to detect one lung ventilation situation. Testing the algorithm on real breathing sounds, which were recorded in a surgery room, shows more than 90% accuracy in OLI detection. PMID- 17271829 TI - Automated extraction of aortic and pulmonary components of the second heart sound for the estimation of pulmonary artery pressure. AB - The second heart sound, S2, is generally believed to be comprised of aortic (A2) and pulmonary (P2) components. Previously, the normalized splitting interval (NSI) between the A2 and P2 components has been shown to be proportional to the pulmonary artery pressure (PAP). A set of fully automated algorithms based on adaptive modeling of A2/P2 components using chirplets were developed to provide real-time estimates of PAP. The method was tested on 16 pigs which were administered drugs to induce pulmonary hypertension. Simultaneous reference pressure measurements were obtained with a pulmonary artery catheter (PAC). Estimation of PAP in pigs using the new techniques resulted in a correlation coefficient (r) of 0.84 and standard error (SEE) of 9.2 mm Hg. This is in line with echocardiography studies, which have a performance ranging from r=0.69-0.91 and SEE from 5 to 12 mm Hg when compared to PAC measurements. It is also consistent with previous results based on a manual estimation of PAP derived through image processing methods. Based on these findings, this method has the potential to offer continuous noninvasive monitoring of PAP. PMID- 17271830 TI - Evaluation of an automatic ocular filtering method for awake spontaneous EEG signals based on independent component analysis. AB - Electroencephalographic artifacts associated with eye movements are a potential source of error in the EEG analysis when its interpretation is performed for evaluating the influence of drugs and the diagnosis of neurological disorders. In this study, a new automatic method for artifact filtering based on independent component analysis (ICA) is proposed. Automatic artifact identification is based on frequency domain and scalp topography aspects of the independent components. A comparative study between ICA and the 'gold standard' method based on linear regression analysis is performed. The latter does not take into account the mutual contamination between EEG and electrooculographic activity, reducing not only the ocular movements but also interesting cerebral activity, mainly in anteriorly placed electrodes. This limitation is overcome by ICA and the efficiency of this approach is shown for a double-blind, placebo-controlled crossover drug trial in healthy volunteers. PMID- 17271831 TI - Noniterative method for two-lead fetal ECG extraction. AB - We propose a novel noniterative technique for fetal electrocardiogram extraction. The polynomial networks technique is used to nonlinearly map the MECG signal recorded at the thorax area to the ECG signals recorded at the abdomen. The FECG component is then extracted by subtracting the nonlinearly mapped MECG component from the abdominal ECG signal. Visual test results obtained from real ECG signals show that the proposed algorithm is capable of reliably extracting the FECG from two leads only. The visual quality of the FECG extracted by the proposed technique is found to meet or exceed that of published results using other techniques. PMID- 17271832 TI - Relation between human alertness, velocity wave profile of saccade, and performance of visual activities. AB - Practical method for assessing human alertness is desired for preventing traffic accidents caused by drowsiness in the drivers. We examined relation between saccade profile (PV/D), which was reported to have dependency on the alertness, and visual activities to investigate an applicability of the saccade for assessing the alertness in vision-dependent circumstances such as driving. We defined a new parameter of visual activity as "bit rate of visual perception (BRVP)", and analyzed relations of saccade velocity profile to the BRVP, relative pupil diameter, and critical fusion frequency. The results showed significant high positive correlations between PV/D, BRVP, and relative pupil diameter. PMID- 17271833 TI - Improved algorithm for ballistocardiac artifact removal from EEG simultaneously recorded with fMRI. AB - The simultaneous recording of electroencephalogram (EEG) and functional magnetic resonance image (fMRI) is a promising tool that is capable of providing high spatiotemporal brain mapping. One of the difficulties to obtain high-quality simultaneous EEG/fMRI data comes from the heartbeat artifact induced in the EEG recorded within fMRI scanner. The purpose of this study was to develop a novel algorithm for removing heartbeat artifact, thus overcoming problems associated with previous methods. Our method consists of a mean artifact waveform subtraction, the selective removal of wavelet coefficients, and a recursive least square adaptive filtering. The recursive least square adaptive filtering operates without dedicated sensor for the reference signal, and only when the mean subtraction and wavelet-based noise removal is not satisfactory. The performance of our system has been assessed using simulated data based on experimental data of various spectral characteristics, and actual experimental data of alpha-wave dominant normal EEG and epileptic EEG. PMID- 17271835 TI - Computationally efficient velocity profile solutions for cardiac haemodynamics. AB - This work reformulates the nonlinear differential equations associated with time varying resistance in minimal cardio-vascular system models into a system of linear equations with an analytical solution. The importance of including time varying resistance is shown for a single chamber model where there is a 17.5% difference in cardiac output when compared with a constant resistance model. However, the increased complexity has significant extra computational cost. This new formulation provides a significant computational saving of 15x over the previous method. This improvement enables more physiological accuracy with minimal cost in computational time. As a result, the model can be used in clinical situations to aid diagnosis and therapy selection without compromising on physiological accuracy. PMID- 17271834 TI - Multichannel fusion models for the parametric classification of multicategory differential brain activity. AB - This work introduces multichannel classification fusion and multichannel data fusion models to fully exploit the different but complementary brain activity information recorded from multiple channels. The goal is to accurately classify differential brain activity into their respective categories. A parametric weighted classification fusion model and three weighted data fusion models (mixture, sum, and concatenation) are introduced. Parametric classifiers are developed for each fusion strategy and the performances of the different strategies are compared by classifying 14-channel evoked potentials (EPs) collected from subjects involved in making explicit match/mismatch comparisons between sequentially presented stimuli. The best performance is obtained using multichannel EP concatenation and the performance improves by incorporating weights in the fusion rules. The fusion strategies introduced are also applicable to other problems involving the classification of multicategory multivariate signals generated from multiple sources. PMID- 17271836 TI - Laplacian ECG moment of activation detection algorithm during pacing. AB - Laplacian ECG (LECG) is a new technique for detecting cardiac electrical activity. An algorithm was designed utilizing ECG QRS complexes to determine where cardiac activity was likely present in the LECG. The recurrent property of ECG is exploited by this new algorithm for the detection of the QRS complexes by cross (auto) correlation. Further, the algorithm calculates the time offset of the LECG signal from the ECG peak. This offset is termed the moment of activation (MoA) and is determined automatically. LECG body surface isochronal maps depict information about cardiac activation patterns. Besio related the ECG QRS complex to the LECG isochrones by mapping the body surface MoAs. We now report on an algorithm to increase the efficiency of this method. PMID- 17271837 TI - Synchronization analysis of epileptic ECOG data using SOM-based SI measure. AB - The exact spatio-temporal changes leading to epileptic seizures, although widely studied, are not well understood yet. We propose to investigate the mechanisms leading to epileptic seizures by using a self-organising map (SOM) based similarity index (SI) measure. While it is shown that this measure is statistically as accurate as the original SI measure, it is also computationally faster and therefore applicable for real-time analyses. Application of SOM-based SI measure on epileptic seizure data reveals interesting aspects of synchronization and de-synchronization at various spatio-temporal levels. PMID- 17271838 TI - New approach in developing of the algorithms for resuscitation assistance. AB - The algorithms used in automated external defibrillators (AED) do not provide the necessary reliability of detection of fibrillation, especially in presence of artifacts. The system described in this article allows detecting different artifacts, improving the detection quality. Also an approach is suggested, to extend the AED functions to detect pulseless electrical activity. The new algorithm uses the impedance signal as an additional parameter to diagnose the cardiac arrest. The parallel analysis of ECG and impedance signals allows detecting noise, motion, respiration and hemodynamic parameters. The comparative tests of the algorithm demonstrated the excellent performance of the algorithm. PMID- 17271839 TI - A 3-D boundary element solution to the forward problem of electrical impedance tomography. AB - We describe a 3-D boundary element method (BEM) solution to the electrical impedance tomography (EIT) problem. The long-term goal is to use EIT to reconstruct a conductivity map to be used in the inverse problem of electrocardiography. The principle advantage of a BEM solution to EIT is that it imposes the assumption that the internal organ conductivities are piecewise constant in the volume. This dramatically decreases the number of unknowns. The forward problem of EIT, as we approach it here, is to compute the potentials at electrodes on the body surface, given a set of current patterns injected by those same electrodes and a known conductivity map. We present the application of EIT specific boundary conditions on the BEM equations and report simulations illustrating the effect of some internal inhomogeneities on the EIT forward solution. PMID- 17271840 TI - Interactive neuromonitoring methods of cochlea and auditory nerve during induced hypoxia and nerve manipulation. AB - Methods and instrumentation were developed to monitor cochlea and auditory function during surgery. The system allows real time assessment of the cochlear function during auditory nerve manipulation. A specially designed optic probe, placed on the round window (RW) niche, enables simultaneous acquisition of cochlear blood flow (CBF) and electrocochleogram (ECochG). We developed the acquisition paradigms, signal processing methods and implement them in a computational platform. The neuromonitoring system performs an automatic extraction and analysis of cochlear microphonics (CM), compound action potentials (CAP) and sura mating potential (SP). The system uses envelope detection filters to detect the amplitude of the CM. The CAP signal is processed with zero phase shift spectral filters, tuned to enhance the action potential onset, which is sometimes embedded within the sura mating potential. An automatic peak detection and tracking algorithm is then applied to extract latency and amplitude of CAPs. Long-term assessment of the monitoring system was performed during experimental animal surgeries. The system allowed detailed study of the dynamics of CM, CAP and CBF during nerve manipulation and compression. PMID- 17271841 TI - MMG-based classification of muscle activity for prosthesis control. AB - We have previously proposed the use of "muscle sounds" or mechanomyography (MMG) as a reliable alternative measure of muscle activity with the main objective of facilitating the use of more comfortable and functional soft silicone sockets with below-elbow externally powered prosthesis. This work describes an integrated strategy where data and sensor fusion algorithms are combined to provide MMG based detection, estimation and classification of muscle activity. The proposed strategy represents the first ever attempt to generate multiple output signals for practical prosthesis control using a MMG multisensor array embedded distally within a silicon soft socket. This multisensor fusion strategy consists of two stages. The first is the detection stage which determines the presence or absence of muscle contractions in the acquired signals. Upon detection of a contraction, the second stage, that of classification, specifies the nature of the contraction and determines the corresponding control output. Tests with real amputees indicate that with the simple detection and classification algorithms proposed, MMG is indeed comparable to and may exceed EMG functionally. PMID- 17271842 TI - Identification of cardiovascular dynamics from peripheral circulatory waveform signals using two sensor blind system I.D. AB - A new tool for characterizing systemic and local hemodynamic behavior in real time has been developed. Through the evaluation of two peripheral circulatory waveform measurements (e.g. continuous measurements such as pressure or flow or volumetric change) this new signal-processing algorithm generates two compact, low order models that describe the distinct branch dependent features of the measured circulatory signals. The method employs a multichannel blind system identification (MBSI) technique that has been reformulated to use a Laguerre basis series expansion. The new MBSI approach allows accurate identification of vascular hemodynamics in experimental data measured in a swine model. PMID- 17271843 TI - New idea of hearing aid algorithm to enhance speech discrimination in a noisy environment and its experimental results. AB - A hearing aid can help the hearing impaired to listen to speech by amplifying its sound. However, amplification cannot always improve speech perception. To improve speech perception in a noisy environment, we proposed a new hearing aid algorithm that combines independent component analysis (ICA) with multiband loudness compensation. The proposed method was applied to a behind-the-ear type (BTE) dual microphone hearing aid. The proposed method successfully separated a target speech signal from background noise such as babble, car noise, factory noise. This method may help hearing aid users to hear the speech that he or she wishes to hear clearly in noisy conditions. PMID- 17271844 TI - Functional activity monitoring from wearable sensor data. AB - A novel approach is presented for the interpretation and use of EMG and accelerometer data to monitor, identify, and categorize functional motor activities in individuals whose movements are unscripted, unrestrained, and take place in the "real world". Our proposed solution provides a novel and practical way of conceptualizing physical activities that facilitates the deployment of modern signal processing and interpretation techniques to carry out activity monitoring. A hierarchical approach is adopted that is based upon: 1) blackboard and rule-based technology from artificial intelligence to support a process in which coarse-grained activity partitioning forms the context for finer-grained activity partitioning; 2) neural network technology to support initial activity classification; and 3) integrated processing and understanding of signals (IPUS) technology for revising the initial classifications to account for the high degrees of anticipated signal variability and overlap during freeform activity. PMID- 17271845 TI - Software system for data management and distributed processing of multichannel biomedical signals. AB - The presented software is designed for efficient utilization of cluster of PC computers for signal analysis of multichannel physiological data. The system consists of three main components: 1) a library of input and output procedures, 2) a database storing additional information about location in a storage system, 3) a user interface for selecting data for analysis, choosing programs for analysis, and distributing computing and output data on cluster nodes. The system allows for processing multichannel time series data in multiple binary formats. The description of data format, channels and time of recording are included in separate text files. Definition and selection of multiple channel montages is possible. Epochs for analysis can be selected both manually and automatically. Implementation of a new signal processing procedures is possible with a minimal programming overhead for the input/output processing and user interface. The number of nodes in cluster used for computations and amount of storage can be changed with no major modification to software. Current implementations include the time-frequency analysis of multiday, multichannel recordings of intracranial EEG of epileptic patients as well as evoked response analyses of repeated cognitive tasks. PMID- 17271846 TI - Stepwise model order estimation in blind source separation applied to ictal EEG. AB - Most algorithms for blind source separation (BSS) or independent component analysis (ICA) assume an equal number of sources as sensors. For multichannel electrophysiological recordings, such as the electroencephalogram (EEG), however, there are often far fewer sources of neurophysiologically relevant activity than the number of sensors. This adds a model order estimation problem to the source separation problem. Conventional estimates of the number of sources are based on the dominant eigenvalues of the data covariance matrix, obtained from principal component analysis (PCA), whose corresponding eigenvectors are also used for prewhitening. It is well known that PCA is susceptible to noise, leading to incorrect model order estimates and data distortion, which in turn limit the accuracy of the source estimates. It is therefore highly desirable to determine the correct number of sources and their spatial topographies directly, without PCA-based data truncation or prewhitening. In this work, we present a stepwise BSS method for extracting only the sources necessary for a sufficiently good least-square fit to the data. This simultaneously yields model order and source estimates, which we examine at different noise levels. We also show how only a few neurophysiologically meaningful components can be extracted from 25-channel ictal EEG. PMID- 17271847 TI - MEG source estimation in the presence of low-rank interference using cross spectral metrics. AB - We estimate a source current dipole at a known location in the presence of low rank interference using magnetoencephalography (MEG). We present a space-time processor for MEG data based on the generalized sidelobe canceler (GSC). We extend the classical vector beamformer to a matrix structure without making any assumptions on the rank of the covariance matrix of noise and interference, or constraint matrices. Furthermore, we define the cross-spectral metrics (CSM) in their most general form. The CSM method is known to approximate the performance of the matched filter for the case of unknown covariance matrix. In our case, the CSM also allows to reduce the complexity of the filtering problem without significant loss of performance in the signal-to-interference-plus-noise ratio (SINR). Our results show that good estimates of the dipole sources can be achieved by only using a few eigenvalues, namely, those corresponding to the largest CSM. PMID- 17271848 TI - Mapping scalp topographies of rhythmic EEG activity using temporal decorrelation based constrained ICA. AB - Independent component analysis (ICA) methods are being increasingly applied to the analysis of electromagnetic (EM) brain signals. However, these powerful techniques still generally require subjective a posteriori analysis in order to visualise neurophysiologically meaningful components in the outputs. Standard implementations of ICA are restrictive mainly due to the square mixing assumption (i.e., as many sources as measurement channels) - this is especially so with large multichannel recordings. There are many instances in neurophysiological analysis where there is strong a priori information about the signals being sought; as in tracking the changing scalp topographies of rhythmic activities. Through constraining the ICA solution it is possible to extract signals that are statistically independent, yet which are similar to some reference signal which incorporates the a priori information. We demonstrate this method on a multichannel recording of an epileptiform electroencephalogram (EEG), where we automate the repeated simultaneous extraction of both rhythmic seizure activity, as well as alpha-band activity, over an epoch of EEG. Subjective analysis of the results shows scalp topographies with realistic spatial distributions which conform to our neurophysiologic expectations. This work shows that constraining ICA can be a very useful technique, especially in automated systems and we demonstrate that this can be successfully applied to EM brain signal analysis. PMID- 17271849 TI - Localizing brain interactions from rhythmic EEG/MEG data. AB - The interpretation of MEG/EEG data in terms of brain connectivity is largely obscured by artefacts of volume conduction, i.e. by the fact that a single source is observable in many channels. Here, we analyze a measure which is insensitive to spurious connectivity arising from volume conducted "self-interaction". For rhythmic data such a measure can be given by the imaginary part of the cross spectrum between EEG/MEG channels. For the derivation we essentially exploit that a signal is not time-lagged to itself. To localize the sources of this observed interaction we fit a model cross-spectrum consisting of N interacting dipoles to the sample cross-spectrum. The relation to the maximum likelihood estimator will be discussed in detail. The method is illustrated for MEG data of human alpha rhythm in eyes closed condition. The eigenvalues of the imaginary cross-spectrum clearly indicate the presence of at least 4 necessarily interacting sources. Fits of 2 to 6 dipoles in a realistic volume conductor all resulted in locations scattered in the mesial part of the occipital lobe. PMID- 17271850 TI - Venous catheter based mapping of epicardial ectopic activation. AB - Catheter based electrophysiological studies of the epicardium are limited to regions near the coronary vessels or require transthoracic access. We have developed a statistical approach by which to estimate high-resolution maps of epicardial activation from very low-resolution multielectrode venous catheter measurements. Essential components of this approach are the training data set composition and the catheter electrode locations used to determine the relationship between catheter sites and the remaining measurement sites on the epicardium. We report here on the methods we investigated to show the effect of the content of the training set. Our results showed that the closer the match between features of the maps to be reconstructed and the training data set. the more estimation accurately predicted the earliest site of activation. We also report results from two different approaches to leadset selection by which we obtained similar accuracy levels. The results of this study suggest that reconstructing complete epicardial activation maps from venous catheter based measurements is both feasible and practical for future clinical applications. PMID- 17271851 TI - Electro-mechanical imaging of the heart using tagged MRI and ECG/MCG arrays. AB - We develop a computational framework for estimating simultaneously mechanical properties (active stress, passive elasticities, and mechanical activation time) and electrical properties (current density and electrical activation time.) First, we present a method for estimating the mechanical properties, active stress and passive elasticity modulus, of the in vivo heart using magnetic resonance imaging (MRI) tissue-tagging and intra-ventricular pressure measurements. Next, we present an algorithm for estimating the current density of the heart using electrocardiography (ECG) and magnetocardiography (MCG) sensor arrays. Finally, we present an inverse electro-mechanical model based on the excitation-contraction coupling and dynamic analysis which includes inertial forces and moving mesh. The proposed model has significant potential for studying the coupling effects in the whole heart. PMID- 17271852 TI - Dipole localization using beamforming and RAP-MUSIC on simulated intracerebral recordings. AB - Interpreting intracerebral recordings in the search of an epileptic focus can be difficult because the amplitude of the potentials are misleading. Small generators located near the electrode site generate large potentials, which could swamp the signal of a nearby epileptic focus. In order to address this problem, two inverse problem algorithms, beamforming and recursively applied and projected multiple signal classification (RAP-MUSIC), were used with simulated intracerebral potentials to calculate equivalent dipole positions. Three dipoles were positioned in an infinite plane medium near three intracerebral electrodes. The potentials generated by the dipoles were simulated and contaminated with white noise. Initial localization simulations showed that both methods detected the sources accurately with RAP-MUSIC reporting lower orientation errors. A spatial resolution analysis for both methods was undertaken in which two dipoles were placed on a plane with the same orientation and overlapping time-courses. Beamforming was able to adequately distinguish the sources for separation distances of 1.2 cm, whereas RAP-MUSIC managed to separate the sources for dipoles as close as 0.4-0.6 cm. PMID- 17271853 TI - Dynamic medical imaging as a partial inverse problem. AB - Dynamic medical imaging problems are typically structured as "partial" inverse problems: the desired time series of images (a spatiotemporal matrix) is subject to a purely spatial transformation (its product with a transfer matrix) - so that the forward operator does not address all of the variables of the function to be transformed (analogous to partial differentiation, which is also a partial inverse problem). Given that the transfer matrix is ill-conditioned, the problem of providing the image sequence requires regularization. Under rather general conditions applicable to the setting of partial inverse problems, the regularization parameter of Tikhonov regularization generalizes to a regularization parameter operator, which in proper combination with a standard (spatial) Tikhonov regularizing operator describes the minimum-mean-square-error estimate analogously to that of the Bayesian interpretation of Tikhonov regularization as applied to a "complete" inverse problem. This is in distinction to usual methodology employed for dynamic imaging problems, including usual applications of Tikhonov regularization in this realm, which cannot similarly supply the minimum-mean-square-estimate (under the stated general conditions). The potential power of the implied methodology is illustrated with a numerical example - indicating that substantial improvements in solution estimation are possible. PMID- 17271854 TI - Bootstrap-based statistical thresholding for MEG source reconstruction images. AB - This work proposes a bootstrap-based statistical method for extracting target source activities from MEG/EEG source reconstruction results. The method requires measurements in a control condition, which contains only nontarget source activities. The method derives, at each pixel location, an empirical probability distribution of the nontarget source activity using bootstrapped reconstruction obtained from the control period. The statistical threshold that can extract the target source activities is derived based on the empirical distributions obtained from all pixel locations. Here, the multiple comparison problem is taken into account by using two step procedure: studentizing these empirical distributions and deriving an empirical distribution of the maximum pseudo T value at each pixel location. The results of numerical experiments are presented to demonstrate the method's effectiveness. PMID- 17271855 TI - Shear waves induced by moving needle in MR elastography. AB - Magnetic resonance elastography (MRE) is a phase contrast-based method for observing shear wave propagation in a material to determine its stiffness. The objective of this study was to determine whether shear waves suitable for MRE could be induced using a moving acupuncture needle. Tissue-simulating bovine gel phantom and a 0.4 mm diameter acupuncture needle were used in the experiment. The results showed that observable shear waves could be induced in the gel phantom by cyclic needle motion. The observed wavelength varied with excitation frequency, as expected. Generating shear waves using moving needles may be a useful tool to study the basic mechanism of acupuncture with MRE. Further study will be conducted to observe the wave motion in inhomogeneous media and acupuncture induced effects in in-vivo studies. PMID- 17271856 TI - Development of a magnetic resonance elastic microscope system. AB - Magnetic resonance elastography (MRE) is a method that can visualize the propagating acoustic strain waves in elastic materials under mechanical excitation. The local quantitative values of shear modulus are derived from the acquired data. The MRE could improve early detection of pathology because it is known that malignant tumors tend to be much harder than normal tissues and most benign tumors. In order to observe tissues such as the early stage of tumors in mouse embryo, spatial resolution of the MRE image is not enough because of hardware limitation of the conventional MRI system. We developed the elasticity measurement system using the MR microscope which spatial resolution is about 200 mm. The external vibration system and MR pulse sequences are developed for an MR elastic microscope. Experiments were performed with homogeneous and heterogeneous agarose gel phantoms. These results suggest the developed MR elastic microscope system makes it possible to generate image that depict distribution of stiffness. PMID- 17271857 TI - MRI-guided laser thermal ablation: model to predict cell death from MR thermometry images for real-time therapy monitoring. AB - Solid tumors and other pathologies can be treated using laser thermal ablation under interventional magnetic resonance imaging (iMRI) guidance. We developed a model to predict cell death from MR thermometry measurements and applied it to in vivo rabbit brain data. To align post-ablation T2-weighted spin-echo MR lesion images to gradient echo MR images, from which temperature is derived, we used a registration method that aligned fiducials placed near the thermal lesion. We used the outer boundary of the hyperintense rim in the post-ablation MR lesion image as the boundary for cell death, as verified from histology. Model parameters were simultaneously estimated using an iterative optimization algorithm applied to every interesting pixel in 328 images from multiple experiments having various temperature histories. For a necrotic region of 766 voxels across all lesions, the model gave a voxel specificity and sensitivity of 98.1% and 78.4%, respectively. Median distance between the segmented necrotic boundary and the mislabeled voxels was within one MR voxel. Furthermore, our model predicted fewer errors as compared to the critical temperature cell death model. This is good evidence that iMRI temperature maps can be used with our model to predict therapeutic regions in real-time. PMID- 17271858 TI - T1rho relaxation quantification using spiral imaging: a preliminary study. AB - Osteoarthritis (OA) is a disease of articular cartilage degeneration. Early detection of changes in cartilage would be essential for preventing the progression of disease and for monitoring therapy in OA. The T/sub 1rho/ relaxation parameter describes the spin-lattice relaxation in the rotating frame and has been considered as a promising tool to detect the loss of proteoglycan (PG), which is an early precursor of OA. The goal of this study was to develop a T/sub 1rho/-weighted imaging method based on spiral imaging and to examine the feasibility of applying it to in vivo cartilage imaging. T/sub 1rho/-weighted imaging with a pre-encoded spin-lock pulse cluster followed by a spiral acquisition sequence was implemented on GE 1.5 T scanners. tip maps were generated by a pixel-by-pixel fit of the T/sub 1rho/-weighted data to an exponential decay. Homogeneous agarose phantoms and the patella cartilage of one healthy volunteer were imaged using the developed techniques. T/sub 1rho/ in agarose phantoms decreased as agarose concentration increased. No significant tip dispersion was seen within spin-lock frequencies ranging from 150 Hz to 1000 Hz in agarose phantoms. T/sub 1rho/-weighted images of the healthy volunteer showed good contrast between cartilage and surrounding tissues. The fitted T/sub 1rho/ value of patella cartilage was within the range of 30-100 ms. PMID- 17271859 TI - Diffusion PDE-based denoising technique for magnetic resonance electrical impedance tomography. AB - Recent progress in magnetic resonance electrical impedance tomography (MREIT) research has shown that conductivity images with higher spatial resolution and accuracy are achievable. One of the most important remaining problems to be solved in MREIT before we can apply the technique to human subjects is how to reduce the amount of injection current. Since we use an MRI scanner to measure the induced magnetic flux density data subject to an injection current, the data is contaminated with random noise. In order to obtain enough signal-to-noise ratio (SNR), we need to inject a large amount of current into the subject. However, it is obvious that we must comply with the electrical safety regulations and this means that we should deal with noisy data having a low SNR due to the limited amount of injection current. Furthermore, in the developed reconstruction algorithms, the required numerical differentiations of the noisy data may result in deterioration of the reconstructed conductivity image leading to a loss of important information. We propose a PDE-based denoising technique that diminishes the degradation of reconstructed conductivity images due to the noise in measured data. The proposed PDE-based technique is advantageous in reducing the random noise while preserving useful features in MREIT. PMID- 17271860 TI - Identifiability analysis of the standard pharmacokinetic models in DCE MR imaging of tumours. AB - The usage of dynamic contrast-enhanced MRI (DCE-MRI) as a clinical tool is still widely assessed. Application of the standard pharmacokinetic models to obtain physiologically relevant parameter values using DCE-MRI in tumours is not trivial, when the temporal resolution is low. Mathematical analysis and analysis by simulation of the identifiability for the generalized and extended Kety models was executed. Parameter estimation was executed using synthetic data sets and maximum likelihood estimation (MLE). The influence of temporal resolution was examined. The generalized and extended Kety model showed a large bias in the parameter estimates (10-120%) for sampling times >4 s, although the estimated variance was relatively low (<1%). This was in accordance with the generated contour plots of the hyperplane of the MLE cost-function. The influence of measurement noise on the input and output turned out to be less significant than the temporal resolution. PMID- 17271861 TI - Adapting MRI systems to propel and guide microdevices in the human blood circulatory system. AB - Magnetic resonance imaging (MRI) systems are widely used to gather noninvasively images of the interior of the human body. This paper suggests that an MRI system can be seen beyond being just a tool for imaging purpose but one that can propel and guide special microdevices in the human body to perform specific medical tasks. More specifically, an MRI system can potentially be used to image the region of interest, propel a microdevice through the generation of magnetic gradients, determine the location of the device, compute the corrective actions through feedback control algorithms and adjust the generation of the magnetic gradients accordingly to navigate such a microdevice in a preplanned path. This paper presents an introductory description of the proposed techniques, the main issues to consider, and some preliminary data indicating the validity of this approach. PMID- 17271862 TI - Flexible real-time magnetic resonance imaging framework. AB - The extension of MR imaging to new applications has demonstrated the limitations of the architecture of current real-time systems. Traditional real-time implementations provide continuous acquisition of data and modification of basic sequence parameters on the fly. We have extended the concept of real-time MRI by designing a system that drives the examinations from a real-time localizer and then gets reconfigured for different imaging modes. Upon operator request or automatic feedback the system can immediately generate a new pulse sequence or change fundamental aspects of the acquisition such as gradient waveforms excitation pulses and scan planes. This framework has been implemented by connecting a data processing and control workstation to a conventional clinical scanner. Key components on the design of this framework are the data communication and control mechanisms, reconstruction algorithms optimized for real-time and adaptability, flexible user interface and extensible user interaction. In this paper we describe the various components that comprise this system. Some of the applications implemented in this framework include real-time catheter tracking embedded in high frame rate real-time imaging and immediate switching between real-time localizer and high-resolution volume imaging for coronary angiography applications. PMID- 17271863 TI - Parallel generalized series MRI: algorithm and application to cancer imaging. AB - MRI is a relatively slow imaging technique. Although imaging speeds have increased dramatically over the last three decades, many clinical and research applications, ranging from contrast-enhanced dynamic imaging of breast tumors to cardiac imaging, require still faster imaging methods. To address this problem, this paper presents a novel algorithm to integrate generalized series (OS) imaging with parallel imaging using multiple receiver coils. This algorithm takes advantage of both the conventional parallel data acquisition scheme and the GS model-based reduced-scan imaging method to achieve higher spatiotemporal resolution in dynamic imaging. The algorithm has been validated using both simulated and experimental data from dynamic contrast-enhanced MRI experiments, which produced excellent results. We expect the algorithm to be useful for a number of dynamic imaging applications, especially contrast-enhanced imaging of tumors. PMID- 17271864 TI - On Tikhonov regularization for image reconstruction in parallel MRI. AB - Parallel imaging using multiple receiver coils has emerged as an effective tool to reduce imaging time in various MRI applications. When a large number of receiver channels are used to achieve large acceleration factors, the image reconstruction problem can become very ill conditioned. This problem can be alleviated by optimizing the geometry of the coils or by mathematical regularization. Among the regularization methods, the Tikhonov scheme is most popular because of rough Gaussianity of the data noise, the easiness to incorporate prior information, as well as the existence of a closed-form solution. A central issue in implementing the Tikhonov scheme is the choice of the regularization parameter and the regularization image, which is addressed systematically in this paper. A new algorithm is also proposed for generating the regularization image and selecting the regularization parameter. Experimental results will be shown to demonstrate the performance of the algorithm. PMID- 17271865 TI - Overcoming phase effects of voxel-sized coils in planar and cylindrical arrays. AB - Parallel imaging in MRI (using multiple coils to partially encode k-space) is currently the primary route to decreasing scan time. Single echo acquisition (SEA) imaging is a completely parallel imaging method recently developed by our group that collects a full image in a single echo. Phase encoding is eliminated and replaced by the spatial localization of long and very narrow coils. The fact that the coils are on the order of the voxel size for the first time in an MR application has led to an examination of the effect of the phase of the coil on the signal received from the voxel and how to most effectively manipulate it. Obtaining full signal from a voxel in planar arrays can be accomplished with a single gradient compensation pulse, but the phase effects in cylindrical arrays are more complex due to the changing coil angle with regard to the Cartesian axes of the gradients. This paper discusses the signal-phase interactions of planar and cylindrical arrays of voxel-sized coils and suggests methods for phase manipulation for optimization. PMID- 17271866 TI - Adaptive SENSE reconstruction for parallel imaging with massive array coils. AB - This work presents an adaptive SENSE reconstruction method for parallel magnetic resonance imaging with a large number of localized coils. This method uses a Gaussian model to obtain improved coil sensitivity estimate. For image reconstruction, it dynamically selects a subset of receiver channels, in a pixel by-pixel fashion, to improve computational efficiency and the signal-to-noise ratio (SNR). Computer simulations and real experiments show that the proposed method reconstructs images with reduced artifacts and higher SNR than the SENSE method. PMID- 17271867 TI - Transmitting focused B/sub 1/ field and SENSE reconstruction using an 8-element transceive torso phased array coil. AB - In this work, a new design concept in chest imaging for MRI application is presented. A focused, 8-element transceive torso phased array coil is designed to investigate transmitting focused B/sup 1/ field deep within the torso to enhance signal intensity and use in conjunction with SENSE reconstruction technique. Hybrid FDTD/MOM method is used to accurately predict the RF behavior inside the human torso. The simulation results reported herein demonstrate the feasibility of the design concept which shows that B/sub 1/ field focusing with SENSE reconstruction is achievable, and the 8-element transceive torso phased array coil has the advantage to be used in transmit and receive mode for optimum and fast chest imaging. PMID- 17271868 TI - Quantitative assessment of parallel acquisition techniques in diffusion tensor imaging at 3.0 Tesla. AB - Single shot echo-planar based diffusion tensor imaging is prone to geometric and intensity distortions which scale with the magnetic field. Parallel imaging is a means of reducing these distortions while preserving spatial resolution. A quantitative comparison at 3 T of parallel imaging for diffusion tensor sequences using k-space (GRAPPA) and image domain (SENSE) reconstructions is reported here. Indices quantifying distortions, artifacts and reliability were compared for all voxels in the corpus callosum and showed that GRAPPA with an acceleration factor of 2 was the optimal sequence. PMID- 17271869 TI - MR-tomography on patients with heart pacemakers-a numerical study. AB - Patients having a heart pacemaker are not allowed to go to MR tomography (MRT). One of the most dangerous effects is the heating of the tissue around the electrode caused by the coupling to the RF field of the MR system. Experiments have been carried out using tanks filled with saline water and large heating has sometimes been observed. Other experiments e.g. with electrodes in the brain did not show any heating at all. In this work numerical studies have been carried out to understand the different results. In conclusion it is suggested that MRT could be possible if the "normal" geometry of the wires of a heart pacemaker is ensured and an open MR system is used. PMID- 17271870 TI - Robust fiber tracking method by vector selection criterion in diffusion tensor images. AB - One of the most important applications of diffusion tensor image (DTI) is the in vivo investigation of brain white-matter connectivity. However, DTI has difficulties on the reconstruction of axonal fibers. The data that is used to reconstruct the fibers is affected by partial volume effect, particularly at the border between gray and white matter, and the typical voxel size used in the acquisition of the MR images is larger than the characteristic size of the axonal fiber. The proposed vector criterion tracking method uses selective eigenvector interpolation for fiber tracking. As a result, the method produces faster and more stable trajectories with reducing memory consumption, compared to other current methods. PMID- 17271871 TI - Improving spatial signal homogeneity in MR 2D chemical shift imaging using outer volume saturation bands. AB - Many endeavors of improving chemical shift imaging (CSI) techniques have been made during last two decades. Good examples of two-dimensional CSI and three dimensional CSI can be found in the literature. However, clinical CSI using available sequences is still not satisfactory. The purpose of this study was to assess the effect of outer volume saturation bands on signal homogeneity in MR 2D chemical shift imaging. The 2D CSI scans were acquired using a point resolved spectroscopy (PRESS) CSI sequence on a phantom filled with brain metabolites. A single PRESS volume of interest was prescribed graphically. The acquisition matrix was 18x18 phase encodings over a 24-cm FOV. Identical acquisitions were obtained with and without outer-volume saturation bands. After initial acquisition was obtained, four more acquisitions were repeated for both studies with and without saturation bands. Identical five groups of voxels were compared for both studies. Standard deviations of metabolite ratios were calculated in each group for both studies. Spectra obtained without outer-volume saturation bands showed signal to noise gradient with higher concentration of signal within voxels at the center of the volume of interest. Outer volume saturation bands reduced this gradient. In general, standard deviations of metabolite ratios with saturation bands were smaller than those without saturation bands. Improved spatial homogeneity of spectra in voxels of CSI with saturation bands was obtained. Outer-volume saturation bands improve spatial signal homogeneity of chemical shift imaging. PMID- 17271872 TI - Numerical simulation of trabecular bone magnetic resonance imaging. AB - A numerical simulation of trabecular bone structure MR imaging is described. The input of the model is derived from synchrotron 3D muCT trabecular bone images with a resolution of 14mummu14mumx14mum. The static magnetic field perturbation in the bone sample induced by the differences in magnetic susceptibility values between mineralized bone and bone marrow is computed and the MRI experiment for a selected imaging sequence is modeled. PMID- 17271874 TI - Repeatability and variability of noise generated during MRI. AB - Acoustic noise has always been associated with MRI and fMRI. During clinical use, the noise provides a source of irritation to both patients and operators. Within research imaging, the noise creates errors in fMRI, especially for fMRI involving auditory stimulus. Prior studies have attempted to reduce the noise received by subjects using active noise cancellation and statistical prediction algorithms to determine what antinoise to emit, resulting in sound pressure level (SPL) attenuation of 4 to 30 dB. This paper proposes that the noise generated during imaging does not vary on a session by session basis. This should allow a recording of the noise to be used in active noise cancellation instead of predictive algorithms. PMID- 17271873 TI - Applying the transient error reconstruction algorithm in the assessment of the cerebral blood flow. AB - The brain perfusion level, characterized by the cerebral blood flow (CBF) parameter, is a known indicator of blood supply in cerebral ischemic stroke. In magnetic resonance dynamic susceptibility contrast (DSC) perfusion studies the CBF parameter is estimated from the residue function obtained from deconvolving the tissue concentration curve by the arterial concentration curve. Deconvolution is a noise sensitive process and ensuring algorithmic stability leads to CBF biases. Distortions are introduced by noise reducing techniques in both the time domain singular value decomposition (SVD) and frequency-domain based Fourier transform (FT) deconvolution approaches. We provide preliminary results of using the transient error reconstruction algorithm (TERA), an auto regressive moving average based technique, to compensate for these distortions. TERA is applied to determine the characteristics of the low-noise low frequency components of the residue function and then used to reconstruct the time-domain residue function. Results using noise-free signals indicate that the CBF estimates determined using TERA were less sensitive to the tissue mean transit time (MTT) than the time domain SVD techniques. The difficulties encountered when applying TERA approach to signals with noise levels commonly found in MR perfusion studies are also discussed. PMID- 17271875 TI - An inverse problem for reduced-encoding MRI velocimetry in potential flow. AB - We propose a computational technique to reconstruct internal physiological flows described by sparse point-wise MRI velocity measurements. Assuming that the viscous forces in the flow are negligible, the incompressible flow field can be obtained from a velocity potential that satisfies Laplace's equation. A set of basis functions each satisfying Laplace's equation with appropriately defined boundary data is constructed using the finite-element method. An inverse problem is formulated where higher resolution boundary and internal velocity data are extracted from the point-wise MRI velocity measurements using a least-squares method. From the results we obtained with approximately 100 internal measurement points, the proposed reconstruction method is shown to be effective in filtering out the experimental noise at levels as high as 30%, while matching the reference solution within 2%. This allows the reconstruction of a high-resolution velocity field with limited MRI encoding. PMID- 17271876 TI - Parametric imaging in dynamic susceptibility contrast MRI-phantom and in vivo studies. AB - Possibility of quantitative perfusion imaging with DSC MRI is still under discussion. In this work, the quantitative related parameters are analyzed and DSC-MRI limitations are discussed. It includes investigation of measurement procedures/conditions as well as parametric image synthesis methodology. The set of phantoms was constructed and used to inspect the role of Gd-DTPA concentration estimation by EPI measurements, the influence of partial volume effect on concentration estimation, the role of a phantom and its pipes orientation, etc. Additionally, parametric image synthesis methodology was investigated by analysis of influence of a bolus dispersion, bolus arrival time, and other signal parameters on an image quality. As a conclusion testing software package is proposed. PMID- 17271878 TI - SENSE reconstruction with inaccurate sensitivity functions: effects and remedies. AB - Image reconstruction in parallel imaging using an array of phased receiver coils involves solving a matrix equation whose coefficient matrix is formed from estimated coil sensitivity functions. Inaccurate sensitivity functions can create image artifacts and reduce signal-to-noise ratio (SNR). This paper discusses the effects of inaccurate sensitivity functions and proposes some remedies to reduce these effects. Specifically, a spatially varying wavelet denoising method is proposed to improve the accuracy of the estimated sensitivity maps, and a constrained reconstruction method is used to incorporate a priori information about the location of the regions of interest to further improve the SENSE reconstruction. PMID- 17271877 TI - Applications of RF current sources for transmit phased array. AB - Current practice in MRI trends towards higher static magnetic field (B/sub 0/) because of the advantage of signal-to-noise ratio (SNR). However at high magnetic fields, the interaction between a coil and a load becomes significant, thus making current distribution on RF coils disturbed and causing transverse magnetic (B/sub 1/) field inhomogeneity. A novel approach to optimize B/sub 1/, field homogeneity is to use a transmit phased array and adjust the amplitudes and phases of the currents on each element independently. However, independent control is difficult to achieve in conventional arrays due to coupling between elements. In addition, the currents are generally load dependent. In this paper we show that a RF current source is an effective method for controlling the current on each element of the transmit phased array, and that the RF current source is much less sensitive to loading and a interelement coupling than a conventional 50Omega matched coil. PMID- 17271879 TI - An object-oriented designed finite-difference time-domain simulator for electromagnetic analysis and design in MRI. AB - This paper presents a finite-difference time-domain (FDTD) simulator for electromagnetic analysis and design applications in magnetic resonance imaging (MRI). It is intended to be a complete FDTD model of an MRI system including all RF and low frequency field generating units and electrical models of the patient. The framework has been constructed with the assistance of object-oriented concepts. The detailed design procedure is described and the numerical method has been verified against analytical solutions for simple cases and also applied to real field calculations. The simulated results demonstrated that the proposed FDTD scheme can be used to analyze large-scale computational electromagnetic problems in MRI engineering. PMID- 17271880 TI - Numerical evaluation of E-fields induced by body motion near high-field MRI scanner. AB - In modern magnetic resonance imaging (MRI), both patients and radiologists are exposed to strong, nonuniform static magnetic fields inside or outside of the scanner, in which the body movement may be able to induce electric currents in tissues which could be possibly harmful. This paper presents theoretical investigations into the spatial distribution of induced E-fields in the human model when moving at various positions around the magnet. The numerical calculations are based on an efficient, quasistatic, finite-difference scheme and an anatomically realistic, full-body, male model. 3D field profiles from an actively-shielded 4 T magnet system are used and the body model projected through the field profile with normalized velocity. The simulation shows that it is possible to induce E-fields/currents near the level of physiological significance under some circumstances and provides insight into the spatial characteristics of the induced fields. The results are easy to extrapolate to very high field strengths for the safety evaluation at a variety of field strengths and motion velocities. PMID- 17271881 TI - An equivalent distributed magnetic current based FDTD method for the calculation of E-fields induced by gradient coils in MRI. AB - This paper evaluates a low-frequency FDTD method applied to the problem of induced E-fields/eddy currents in the human body resulting from the pulsed magnetic field gradients in MRI. In this algorithm, a distributed equivalent magnetic current (DEMC) is proposed as the electromagnetic source and is obtained by quasistatic calculation of the empty coil's vector potential or measurements therein. This technique circumvents the discretizing of complicated gradient coil geometries into a mesh of Yee cells, and thereby enables any type of gradient coil modeling or other complex low frequency sources. The proposed method has been verified against an example with an analytical solution. Results are presented showing the spatial distribution of gradient-induced electric fields in a multilayered spherical phantom model and a complete body model. PMID- 17271882 TI - An inverse methodology for high frequency RF head coil design with preemphasized B/sub 1/ field in MRI. AB - An inverse methodology to assist in the design of radio-frequency (RF) head coils for high field MRI application is described in this work. Free space time harmonic electromagnetic Green's functions and preemphasized B/sub 1/ field are used to calculate the current density on the coil cylinder. With B/sub 1/ field preemphasized and lowered in the middle of the RF transverse plane, the calculated current distribution can generate an internal magnetic field that can reduce the EM field/tissue interactions at high frequencies. The current distribution of a head coil operating at 4 T is calculated using inverse methodology with preemphasized B/sub 1/ fields. FDTD is employed to calculate B/sub 1/ field and signal intensity inside a homogenous cylindrical phantom and human head. A comparison with conventional RF birdcage coil is reported here and demonstrated that inverse-method designed coil with preemphasized B/sub 1/ field can help in decreasing the notorious bright region caused by EM field/tissue interactions in the human head images at 4 T. PMID- 17271883 TI - Partial volume effect in quantitative magnetic resonance perfusion imaging. AB - In dynamic-susceptibility contrast (DSC) magnetic resonance (MR) perfusion imaging, the cerebral blood flow (CBF) is estimated from the tissue residue function obtained through deconvolution of the contrast concentration functions. However, the reliability of CBF estimates obtained by deconvolution is sensitive to various distortions. Among the most prominent experimental limitations is the image spatial resolution, leading to partial volume effect (PVE), which arises when the size of the voxel exceeds the volume containing the arterial input signal. PVE results in distortion of the arterial input function (AIF), and directly leads to miscalculation of the CBF. This work demonstrates the degree of the CBF estimation bias that could develop as a result of PVE. PMID- 17271884 TI - Truncation effects in SENSE reconstruction. AB - The data truncation effect in Fourier imaging with a single uniform channel is well understood. However, not much work has been done on multichannel parallel Fourier imaging. This paper presents a systematic investigation of this issue. More specifically, it analyzes the truncation effects under both general and specific conditions and compares the result with that of a single uniform channel. PMID- 17271885 TI - Microdevice's susceptibility difference based MRI positioning system, a preliminary investigation. AB - A positioning technique for an endovascular microdevice propelled by magnetic force inside a magnetic resonance imaging (MRI) system is being developed. Positioning options are presented and a magnetic positioning technique is described in more details. Since a magnetic positioning system is deeply dependent on the quality of the measurement modality, we describe the main magnetic field measurement techniques that can be used inside an MRI. Finally, we propose a magnetic positioning system using MRI phase images to measure the magnetic distortion induced by the ferromagnetic body. Positioning results on a 1010/1020 carbon steel, 1.5875 mm diameter sphere with gradient echo phase images are presented. PMID- 17271886 TI - New power loss optimized Fontan connection evaluated by calculation of power loss using high resolution PC-MRI and CFD. AB - A new blood vessel configuration was invented to optimize blood flow efficiency and reduce the power loss in the Fontan connection. The current preferred Fontan configuration, the total cavopulmonary connection (TCPC), usually connects the venae cava (VC) to the pulmonary arteries (PA), bypassing the right ventricle. The new connection, called OptiFlo, has two vertical inlets, which both bifurcate then merge into one another to form two horizontal outlets. One of the preliminary configurations of the new OptiFlo model was used for a comparison experiment between computational fluid dynamics (CFD) and high resolution phase contrast magnetic resonance imaging (PC-MRI) with a voxel resolution of 0.23 mmx0.23 mmx0.25 mm. The thin slice thickness was achieved using the ACGI interpolation technique we have used in other applications before. The 2D PC-MRI velocity vectors were mapped into a CFD grid, enabling direct CFD and MRI data comparisons. The mean squared difference was found between the two dataset Using the viscous power dissipation function we calculated the power loss for both CFD and MRI data. The power losses, calculated with the viscous power dissipation function, were 0.66 mW for CFD and 0.46 mW for the PC-MRI data. PMID- 17271887 TI - A Novel open-ended intravascular MRI loop probe. AB - Recently, intravascular catheter probes have been developed to increase SNR for MR imaging of coronary arteries. Miniaturization of these catheter probes without degrading their performances is very essential in imaging small arteries. Since both signal and noise received by intravascular loop probes are of low level, the noise generated by the cable connecting the probe to the matching circuit may reduce SNR significantly. Therefore, the tuning and matching circuit must be placed very close to the loop probe, which restricts its miniaturization and flexibility. We propose a novel open-ended loop probe for 64 MHz with an input impedance of 20 Ohm and a length of only 4 cm in the bare case. This has two advantages. Firstly, the matching and tuning circuits of the proposed probe can be located outside the vessel. Secondly, its signal level and uniformity is superior to that of the conventional loop antennas. PMID- 17271888 TI - Novel double-turn loop probe for intravascular MRI. AB - Key challenges for design of intravascular loop probes are minimization of the cross sectional and length while increasing signal-to-noise ratio (SNR). Although NPO grade captors under 1mm dimensions are now available, the impedance matching network components still constrain tunability. In this study, a new loop probe is proposed for intravascular magnetic resonance imaging (MRI) at 1.5 Tesla. The new design is based on a two-turn loop, separated by a gap, which can be placed over a perfused inflatable balloon structure. The length and impedance of the probe are 1.1 cm and 23.5OHM (bare case), respectively. The SNR of the new probe is greater than the conventional loop probe. To evaluate the performance of the probe, a series of SNR, length, and impedance comparisons with the conventional loop probes are carried out. PMID- 17271889 TI - Classification of breast thermal images using artificial neural networks. AB - In this paper we present classification of the thermal images in order to discriminate healthy and pathological cases during breast cancer screening. Different image features and approaches for data reduction and classification have been used. The most promised method was based on wavelet transformation and nonlinear neural network classifier. PMID- 17271890 TI - Analysis of breast thermography with an artificial neural network. AB - Thermal imaging has been used for early breast cancer detection and risk prediction since the sixties. Examining thermograms for abnormal hyperthermia and hyper-vascularity patterns related to tumor growth is done by comparing images of contralateral breasts. Analysis can be tedious and challenging if the differences are subtle. The advanced computer technology available today can be utilized to automate the analysis and assist in decision-making. In our study, computer routines were used to perform ROI identification and image segmentation of infrared images recorded from 19 patients. Asymmetry analysis between contralateral breasts was carried out to generate statistics that could be used as input parameters to a backpropagation ANN. A simple 1-1-1 network was trained and employed to predict clinical outcomes based on the difference statistics of mean temperature and standard deviation. Results comparing the ANN output with actual clinical diagnosis are presented. Future work will focus on including more patients and more input parameters in the analysis. Performance of ANN network can be studied to select a set of parameters that would best predict the presence of breast cancer. PMID- 17271891 TI - A comparative study of thermal texture mapping in benign and malignant breast diseases. AB - The aim is to investigate differences of thermal texture mapping (TTM) between benign and malignant breast diseases. After receiving TTM, 100 patients were categorized into three groups in normal patient, benign change and malignant lesion. TTM demonstrated that the malignant lesion mostly appeared thermal features and deeper layer position with surrounding or penetrating vessels, and irregular thermal spread pattern with spinal margin in breast; there also appeared deeper layer abnormal thermal source in axilla and abnormal thermal pattern with circular, asteroid and agaric-like shape fixed near the left side of Angle of Louise of the sternum, which was irrelative to abnormal thermoradiation and lesion position in breast. Therefore, the difference of TTM appearance definitely exists between benign and malignant breast diseases. PMID- 17271892 TI - Analysis of breast diseases examination with thermal texture mapping, mammography and ultrasound. AB - This paper will compare diagnostic values of thermal texture mapping (TTM), mammography and ultrasound in relating breast disease. Using pathological finding as gold standard, the results were compared with that of TTM, mammography and ultrasound. There being 25 cases of malignant and 13 cases of benign, the correlation rate of TTM with pathological finding (100%, 96%) respectively, were superior to the correlation rate of mammography , ultrasound with pathological finding (88.9%, 63.6%, 90.5%, 63.6%). TTM, on the differential diagnosis of breast disease, were superior to mammography and ultrasound. PMID- 17271893 TI - Multimodality data fusion aids early detection of breast cancer using conventional technology and advanced digital infrared imaging. AB - The fusion of data from the various screening modalities will lead to a cost effective breast cancer detection system that is certain to improve the early part of early breast cancer detection methods. We explore the integration of data from mammography, ultrasound, clinical evaluation, and CAD, with noninvasive digital infrared imaging data from the BreastScan IR system, to improve early diagnosis. This will address a new solution to the screening of young women and women with dense breasts. PMID- 17271894 TI - Nondestructive testing of the human breast: the validity of dynamic stress testing in medical infrared breast imaging. AB - The validity of the autonomic cold challenge for use in screening breast thermography is reviewed. A review of the literature is discussed along with reasoning for the choice of the cold stress method used. Breast thermogram results from 23 patients with histologically confirmed breast cancers are presented demonstrating positive and negative responses to the challenge. Cold challenge responses from 500 patients without breast cancer and with normal and persistent abnormal thermograms are also discussed. The question is posed, should the use of the cold challenge be continued considering that a negative response does not rule out the possibility of neoplasm nor does a positive response guarantee its existence? Conclusions are drawn from the available data that suggest that the use of the cold challenge be left up to the discretion of the interpreting thermologist and not mandated with every breast thermogram. Until further studies are performed and ample evidence can be presented, a review of the available data indicates that infrared imaging of the breast can be performed excluding the cold challenge without any known loss of sensitivity or specificity in the detection of breast cancers. PMID- 17271895 TI - Stress infrared telethermography is useful in the diagnosis of complex regional pain syndrome, Type I (formerly reflex sympathetic dystrophy). AB - The objective of this paper is to assess the sensitivity, specificity, and predictive value (PV) of stress infrared telethermography (IRT) in the Complex Regional Pain Syndrome, Type I (CRPS-I). One hundred eighty-five consecutive patients (47 men, 138 women) with 205 pairs of chronically painful limbs (upper, lower, or both) were examined by pain specialists in neurology, physiatry, and anesthesia, who then reached a consensus diagnosis. A clinical diagnosis of CRPS I required at least two of the following observations: burning pain, vasomotor changes, diaphoresis, trophic changes, allodynia. Patients with only one criterion were classified as possible CRPS-I; those with none were judged not to have CRPS-I. Patients and 24 asymptomatic control subjects underwent stress IRT, which was considered positive for CRPS-I if it showed three of the following: quantitative thermal emission of >1.00 degrees C, abnormal distal thermal gradient patterns, presence of a "thermal marker", and abnormal response to functional cold water autonomic stress testing. By clinical criteria, CRPS-I was diagnosed in 73 pairs of limbs; not CRPS-I was diagnosed in 70; and 62 pairs had possible CRPS-I. Excluding possible CRPS-I cases, there were 5 false-negative stress IRTs (sensitivity 93%) and 7 false-positive results (specificity 89%). Based on estimated 50% prior probability for our population, the positive PV is 90% and the negative PV 94%. None of the control subjects exhibited thermographic evidence of CRPS. It is concluded that the stress IRT is a sensitive and specific indicator of CRPS-I. PMID- 17271896 TI - Limitations of active dynamic thermography in medical diagnostics. AB - The problem of validity of active dynamic thermography (ADT) imaging in medical diagnostics is discussed. Practical applications of ADT in medicine are known where synthetic pictures are defined and calculated for objective, quantitative data visualization as well as first attempts of thermal tomography based on ADT are published. In both cases the same sources of errors are influencing quality of measurements and reconstruction data. The main limitations of the methods are here highlighted. The ways, how to avoid misunderstanding of the measurement data are commented. Practical examples of using SW and LW cameras in ADT diagnostics are discussed. PMID- 17271897 TI - Standardization of infrared imaging. AB - To provide an atlas and database for the temperature distribution of the skin in normal human subjects aged from 10 years to 75 years. The technique used in digital infrared thermal imaging which has been in use since 1960. Despite, many different applications and published studies, a normal database is not available. It is particularly needed for forensic and hospital clinic use. PMID- 17271898 TI - Content-based image retrieval for medical infrared images. AB - Past efforts on the automated processing on medical infrared images has typically focused on specialized applications like the detection of breast cancer. We propose the application of content-based image retrieval (CBIR) to medical thermal images. CBIR allows the retrieval of similar images based on features directly extracted from the image data. Hence, image retrieval for a thermal image that shows symptoms of a certain disease will provide visually similar cases which will usually also represent similarities in medical terms. The image features we propose for this purpose are a set of moment invariants of the grayscale thermal images. PMID- 17271899 TI - Functional infrared imaging in the diagnosis of the myofascial pain. AB - Functional infrared imaging has been used to study 17 patients, affected by myofascial pain, and 19 healthy subjects during maximal voluntary clenching (MCV). Aim of the study was to attempt to discriminate patients from healthy subjects through the analysis of the skin temperature distribution and its change during the clenching. The prestress and the post-stress temperatures were evaluated bilaterally for several regions of interest. We calculated differences in temperature between sides (DeltaTs) at each time (pre and post), and between times (DeltaTt) for each side (left and right). Subsequently, we compared DeltaTs and DeltaTt between the healthy and myofascial pain groups. DeltaTs was significantly higher in sufferers compared to healthy people (p<0.05) for both types of evaluation (by side and by time). DeltaTs was significantly different for masseter and sternocleidomastoid, whereas DeltaTt was higher in almost all sites (masseter, sternocleidomastoid, cervical and upper trapezius). Healthy subjects, undergoing MVC, showed the lowest DeltaT value variability, suggesting that temperature remained constant despite the induced physical exercise. Functional infrared imaging seems to distinguish healthy subjects from the patients suffering myofascial pain in almost all the investigated sites. PMID- 17271900 TI - Qualitative thermograhic analysis of psoriatic skin lesions. AB - Psoriasis vulgaris affects about 2% of the human population all over the world. The aim of this study was to evaluate usefulness of thermography in estimation of psoriatic lesion activity. A series of patients with plaque type psoriasis vulgaris were included. ThermaCam INFRAMETRICS 290E thermocamera with temperature resolution of 0.1 degrees C was employed. Both visual and thermal images of the patients were taken. Clinical severity of the lesions was evaluated by Plaque Severity Score (PSS, scale 0-4). We discovered higher temperature over psoriatic plaques and further vastly expanding beyond the visually documented borders of the lesions thus not corresponding to the individual shapes of the lesions, suggested that those lesions presented an active phase of the disease (developing over the last 2-3 weeks). To the contrary, areas of the increased temperature over chronic psoriatic plaques (already developed at least 8 weeks before without signs of visible progression) corresponded quite well to the shapes of clinically visible lesions i.e. single lesions could be differentiated within the area of the increased temperature. The above observations would allow to introduce more aggressive local treatment only to the selected lesions thus as much as possible sparing the rest of them from probable side-effects. PMID- 17271901 TI - Touchless monitoring of breathing function. AB - We have developed a novel method for noncontact measurement of breathing function. The method is based on statistical modeling of dynamic thermal data captured through an infrared imaging system. The expired air has higher temperature than the typical background of indoor environments (e.g., walls). Therefore, the particles of the expired air emit at a higher power than the background, a phenomenon which is captured as a distinct thermal signature in the infrared imagery. There is significant technical difficulty in computing this signature, however, because the phenomenon is of very low intensity and transient nature. We use an advanced statistical algorithm based on the method of moments and the Jeffrey's divergence measure to address the problem. So far, we were able to compute correctly the breathing waveforms for ten (10) subjects at distances ranging from 6-8 feet. The results were checked against concomitant ground-truth data collected with a traditional contact sensor. The technology is expected to find applications in the next generation of touchless polygraphy and in preventive health care. PMID- 17271903 TI - The clinical evaluation of vein contrast enhancement. AB - A vein contrast enhancer (VCE) has been constructed to make vein access easier by capturing an infrared image of veins, enhancing the contrast using software, and projecting the vein image back onto the skin. The VCE also uses software to align the projected image with the vein to 0.06 mm. Clinical evaluation of earlier monitor-based vein enhancement test systems has demonstrated the clinical utility of the infrared imaging technology used in the VCE. PMID- 17271902 TI - Noninvasive infrared imaging for quantitative assessment of tumor vasculature and response to therapy. AB - In this study we are investigating three infrared imaging techniques, thermography, multispectral imaging and Laser Doppler imaging (LDI) to assess parameters of vascularity in lesions of Kaposi's sarcoma (KS) and response to therapy. Thermography, multispectral imaging and LDI were recorded over the lesion and compare to normal skin either adjacent to the lesion or on the contralateral side. The KS lesions generally had increased temperature, blood volume (as measured by multispectral imaging) and blood flux (as measured by LDI) as compare to normal skin. After the treatment with experimental antiKS drug, temperature, blood volume and blood flow of the lesion were significantly reduced from the baseline. These techniques hold promise to assess physiological parameter in KS lesion and their changes with therapy. PMID- 17271904 TI - Self-consistent boundary condition for photon diffusion calculation. AB - The photon diffusion equation has been widely used to assess near-infrared spectroscopy of biological tissues. Here, we introduce the self-consistent boundary condition for the truncated boundary into this calculation. This reduces the effect of the boundary on the results, showing that the self-consistent boundary condition is useful for calculations for analyzing optical topographic images. PMID- 17271905 TI - Immunogold labeling to enhance contrast in optical coherence microscopy of tissue engineered corneal constructs. AB - Our lab has used an optical coherence microscope (OCM) to assess both the structure of tissue-engineered corneal constructs and their transparency. Currently, we are not able to resolve cells versus collagen matrix material in the images produced. We would like to distinguish cells in order to determine if they are viable while growing in culture and also if they are significantly contributing to the light scattering in the tissue. In order to do this, we are currently investigating the use of immunogold labeling. Gold nanoparticles are high scatterers and can create contrast in images. We have conjugated gold nanoparticles to antibodies specific to the alpha/sub 5/beta/sub 1/ integrins expressed in some corneal cells. This choice of target should allow assessment of the phenotypic behavior of the cells in the tissue, as different integrins are expressed in different phenotypes. This study applies the immunogold technique to study cultured corneal cells using the OCM with the ultimate goal of monitoring cellular behavior in engineered tissue and corroborating results from standard histological methods. PMID- 17271906 TI - Use of near-infrared fluorescent dyes in depth resolved spectroscopic optical coherence tomography. AB - Optical coherence tomography (OCT) images of biological tissues often have low contrast. Spectroscopic OCT (SOCT) methods have been developed to enhance contrast. Due to the time-frequency "uncertainty principle" in SOCT signal analysis, minute spectral changes can not be detected for high spatial resolution applications. In order to enhance SOCT contrast in tissues with low inherent spectral absorption, we developed a contrast enhancing technique using near infrared (NIR) dyes. We developed an optimized algorithm for SOCT and an optimum dye concentration for imaging. The effect of contrast enhancement was studied both in tissue phantoms and in situ experiments. Contrast-enhanced images are compared with fluorescence microscopy, demonstrating a link between SOCT and fluorescence imaging. PMID- 17271907 TI - Optical coherence microscopy for the evaluation of a tissue-engineered artificial cornea. AB - A transparent artificial cornea derived from biological material is the ultimate goal of corneal research. Attempts at artificial corneal constructs produced from synthetic polymers have proved unsuccessful due to lack of biocompatibility and ability to integrate into the tissue. We have designed a corneal model derived from collagenous biological materials that has several advantages: it has low antigenicity and therefore small chance of eliciting an immune reaction, it can be broken down by the body's own cells and gradually replaced over time by natural materials, and it may contain signaling information for native cells, thereby inducing normal phenotype and behavior. In addition, a transparent corneal model has the potential to be used for testing of novel ophthalmic drugs or gene therapy approaches, eliminating the need for animal testing. We have used an optical coherence microscope (OCM) to evaluate both the structure of our tissue constructs over time in culture and the optical properties of the tissue itself. This imaging technique promises to be an important diagnostic tool in our efforts to understand the influence of mechanical forces, cell phenotype, and soluble factors on the transparency of corneal tissue. PMID- 17271908 TI - Imaging of human aortic atherosclerotic plaques by polarization-sensitive optical coherence tomography. AB - Optical coherence tomography (OCT) is analogous to ultrasound imaging except that it uses infrared light instead of sound. Polarization-sensitive optical coherence tomography (PS-OCT) combines the advantages of OCT and provides additional image contrast of the tested sample. We demonstrate this technique for imaging of back reflected light, birefringence, and fast-axis orientation simultaneously in different kinds of atherosclerosis plaque. This in vitro study suggests birefringence changes in plaque are due to the prominent deposition of collagen or cholesterol by correlating PS-OCT images with histology. Thus the combination of high resolution structural imaging and birefringence detection make PS-OCT a potentially powerful tool for early assessment of atherosclerosis appearance and prediction of plaque rupture. PMID- 17271909 TI - A tissue phantom for investigating volume quantification on retinal images obtained with the Stratus OCT system. AB - The performance of the Stratus OCT system in extracting shape and volume of retinal lesions was investigated by scanning a tissue phantom containing specific enclosed geometric gaps of known size. Measurements were made by filling the gaps with an aqueous suspension containing a fixed tissue suspended in phosphate buffered saline inside the gaps. OCT raw data was exported for subsequent analysis using custom software written in MATLAB software platform. An active contour model was used to outline the boundaries of the fixed tissue on OCT images of the tissue phantom. Images provided by the OCT system were analyzed with the custom software and later compared with the actual geometric parameters of the tissue phantom. An active contour model is effective in detecting the boundaries of the tested object and accurately estimating its volume. We show that a tissue phantom provides an easy and reproducible method of verifying the accuracy and precision of specific features in the images retrieved by the Stratus OCT system. PMID- 17271911 TI - Surface reconstruction from retinal laser images. AB - The aim of This work is to describe techniques that lead to surface extraction of the retinal structure. Based on the tomographic data from the confocal scanning laser ophthalmoscope (CSLO) we perform some necessary preprocessing steps to correct the nonuniform illumination and to suppress the noise. Then we extract the surface and perform some postprocessing operations before visualization. First results of ongoing research are presented and also the suggestions for future research are proposed. PMID- 17271910 TI - Three dimensional reconstruction of conventional stereo optic disc image. AB - Stereo disc photograph was analyzed and reconstructed as 3 dimensional contour image to evaluate the status of the optic nerve head for the early detection of glaucoma and the evaluation of the efficacy of treatment. Stepwise preprocessing was introduced to detect the edge of the optic nerve head and retinal vessels and reduce noises. Paired images were registered by power cepstrum method and zero mean normalized cross-correlation. After Gaussian blurring, median filter application and disparity pair searching, depth information in the 3 dimensionally reconstructed image was calculated by the simple triangulation formula. Calculated depth maps were smoothed through cubic B-spline interpolation and retinal vessels were visualized more clearly by adding reference image. Resulted 3 dimensional contour image showed optic cups, retinal vessels and the notching of the neural rim of the optic disc clearly and intuitively, helping physicians in understanding and interpreting the stereo disc photograph. PMID- 17271912 TI - An algorithm to detect a center of pupil for extraction of point of gaze. AB - This work proposes an algorithm that is developed for the video-oculograph method. It is used to detect a center of pupil for extraction of point of gaze in the eye image acquired by a charge coupled device camera and TV receiver card. The center of pupil could be detected accurately by applying the proposed algorithm in this study that removes noise effectively caused by eyelashes and image that is projected on pupil. In this study, we assume that the pupil is a perfect circle in the captured eye images. PMID- 17271913 TI - Automated quantification of retinal nerve fiber layer atrophy in fundus photograph. AB - Quantitative analysis of the retinal nerve fiber layer (RNFL) defect is prerequisite in the early detection and management of glaucoma. A new automatic quantification method to evaluate the degree of RNLF defect has been proposed in this paper. Simple image processing technique is applied to locate optic disc and intensity of the pixels around optic disc is plotted. The area with RNFL defect can be easily determined by comparing the intensity plot of the RNFL and the first derivative of the intensity plot. Through analysis of the plot, thickness of RNFL also can be postulated. PMID- 17271914 TI - Auditory hemodynamic studies of newborn infants using near-infrared spectroscopic imaging. AB - The noninvasive study of tissue blood volume and oxygenation using near-infrared light is a new and actively developing technology. We have used near-infrared spectroscopic imaging (NIRSI) to study hemodynamic responses on the auditory cortices evoked by auditory stimulation. Ten healthy newborn infants were studied. The otoacoustic emission hearing test was performed for each infant. Pulse oximetry was used to monitor the heart rate during the measurement, video recording was used to monitor motion artifacts, and the eye movements were noted in order to determine sleep stage. A 16-channel frequency-domain optical imaging system developed in our laboratory was used for NIRSI measurements. The stimuli were presented in trains of seven 1 kHz beeps with 700-ms inter-stimulus intervals. The stimulus trains were separated by 25-s silent periods in order to allow for the hemodynamic delay. In 3/8 cases, we obtained a clear bilateral increase in [HbO/sub 2/], and in two additional cases, a clear response on one hemisphere. The mean change in [HbO/sub 2/] was +0.9+/-0.9muM and the mean change in [Hb] was -0.3+/-0.4muM for those channels producing the largest response for each subject. No statistically significant response was found in 3/8 cases. PMID- 17271915 TI - Time-resolved reflectance of an optical pulse from an adult head model utilizing the finite difference time domain (FDTD) analysis. AB - Time-resolved reflectance of an optical pulse from a four-layered adult head model including cerebrospinal fluid (CSF) has been analyzed based on the finite difference time domain analysis (FDTD) which has been formulated by authors. It has been confirmed that the intensity of the reflected light and the mean time of flight dependences on the source-detector separations estimated from the time resolved reflectance agree quite well with the previously reported experiments and calculations. The sensitivities for detecting optical property changes of gray and white matter beyond CSF in time-resolved reflectance have been evaluated and it has been become clear that they are enhanced compared with the sensitivities in the intensity of the reflected light and the mean time of flight. The derivatives of reflectance with respect to the absorption coefficients of gray and white matter have shown that the presence of CSF improves the capabilities of time-resolved reflectance for detecting optical property changes in the brain in actual noise limited photon detection systems. PMID- 17271916 TI - Blood velocity measurements using laser speckle imaging. AB - Blood velocity measurements in the skin of pigs are reported. Measurements were obtained using laser speckle contrast analysis with a multiple scattering correction. Laser speckle contrast analysis is a rapid technique for obtaining a velocity mapping of perfused tissue. Measurements of blood velocity in pig skin were obtained using a laser and a monochrome digital camera. Blood velocities were measured in tissue prior to and after elevation of flaps. The effect of Iloprost and nitroglycerine on local blood velocity was also examined in nonexcised tissue. PMID- 17271917 TI - Integrated dynamic fluidic lens system for in vivo biological imaging. AB - We have developed an integrated dynamic lens system for in vivo optical imaging. Bioinspired dynamic microfluidic lenses allow for real-time dynamic manipulation of the lens focal length via microfluidic injection into a PDMS membrane-capped chamber. A piezoelectrically actuated micropump is integrated with with the lens to provide highspeed, accurate lens tunability. The 5mm dynamic lens has demonstrated focal length tunability from 8.5mm to 23mm, numerical aperture values from 0.39 to 0.77, and resolution of 40 linepairs/mm. The micropump operates at 5 kHz and achieved a flow rate of approximately 2.4 mL/min. This system can be applied to optical probe techniques to improve diagnosis with real time depth resolution and variable numerical aperture. PMID- 17271918 TI - Oral cancer detection in fluorescent image by color image fusion. AB - Biopsy is the main diagnosis method for oral cancer, which is the fifth most prevalent cancer in male population in Taiwan. In order to increase the accuracy of diagnosis, it is required to reveal the distribution of malignancy prior to biopsy. Based on this purpose, we developed the fluorescent image system associated with color image fusion algorithm to indicate the cancer-susceptible area in the oral image. The system therefore can assist physicians to make appropriate biopsy. PMID- 17271919 TI - Using electrostatic self-assembled gradient nanosensor phantoms for calibration of an optical intrinsic signal imaging system. AB - Wide-field optical intrinsic signal (OIS) imaging has been used in functional cortex mapping for its excellent spatial resolution. To compensate for its low temporal resolution, extrinsic dye signals have been introduced. Fluorescence spectroscopy in the form of nanoengineered sensors has also been used to detect biochemical signals of molecular interactions. In this paper, oxygen-sensitive dye Ru(dpp)/sub 3//sup 2+/ was immobilized into nano-sized spheres by electrostatic layer-by-layer (LbL) self-assembly, and then deposited on glass slides as intensity gradients. By comparing gradient ratios and ratios of function dye Ru(dpp)/sub 3//sup 2+/ and reference dye between epi-fluorescence microscope and an OIS imaging system, the feasibility and efficiency of nano sized oxygen sensors in OIS imaging were studied. PMID- 17271920 TI - High-speed detection of occult tumor cells in peripheral blood. AB - Although detection of tumor cells in peripheral blood using imitiunocytochemistry and optical scanning is a promising method for screening and monitoring cancer, it poses a major technical challenge due to the extremely low tumor cell concentration in blood. The preferred detection method - digital microscopy - is far too slow for analysis of the large numbers of cells required for statistical validity. We describe here a novel prescan instrument that rapidly identifies a small number of candidates for subsequent examination by digital microscopy to determine if they are genuine tumor cells. The prescan is 500 times faster than digital microscopy and yet has a similar sensitivity. The high prescan speed is accomplished by trading resolution for field of view. The resolution of the prescan is determined by the laser spot size of about 10 microns. While this resolution is much coarser than the submicron resolution of microscopes, it is still sufficient for detecting fluorescent cells because it matches the size of a typical cell. The wide field of view and high scan rate are enabled by a novel application of fiber optics. PMID- 17271921 TI - Novel ultra-fast deconvolution method for fluorescence lifetime imaging microscopy based on the Laguerre expansion technique. AB - A new deconvolution method for fluorescence lifetime imaging microscopy (FLIM) based on the Laguerre expansion technique is presented. The performance of this method was tested on synthetic FLIM images derived from a multiexponential model and from fluorescence lifetime standards, and then compared to standard algorithms of FLIM analysis. Our results demonstrated significant advantages of the Laguerre method over standard algorithms. First, the fluorescence intensity decays of arbitrary form can be estimated at every pixel, without a priori assumption of its functional form. Second, the number of delayed images required to perform deconvolution is relatively low (as low as 5), reducing the acquisition time. Third, ultra-fast light sources are not longer required, making less expensive to perform lifetime imaging. Finally and most important, deconvolution at every pixel is performed in parallel using a common Laguerre basis, thus allowing reducing significantly the computation time (i.e. synthetic 600x600 pixel images can be deconvolved with high accuracy in less than 20 s). Based on these findings, we believe that the Laguerre deconvolution technique represents a more robust and extremely fast analytical method that will allow exploring FLIM in practical real-time applications, such as clinical diagnosis. PMID- 17271922 TI - New texture shape feature coding-based computer aided diagnostic methods for classification of masses on mammograms. AB - This work presents new texture shape feature coding (TSFC)-based computer aided diagnostic (CAD) classification methods for classification of masses on mammograms. It introduces a new concept of 1.5-order 3-neighbor 3x3 connectivity to extract texture shape features that can describe multiples of 22.5 degrees . In order to effectively utilize these shape features, two new methods of implementing TFSC are further proposed to convert these features to texture feature numbers (TFNs), TFNs in quaternary (TFNq) which expresses a TFN in quaternary expansion and TFNs in product (TFNx ) that represents a TFN in terms of a product. Both TFNq and TFNx can then produce texture shape histograms in the same way that a gray-level histogram is generated for an image. Such a texture shape histogram is further used to generate various shape features of masses on mammograms for classification. In order to demonstrate the promise of our TSFC based CAD methods, the MiniMammographic database provided by the Mammographic Image Analysis Society (MIAS) is used for experiments. PMID- 17271923 TI - Morphological concentric layer analysis for automated detection of suspicious masses in screening mammograms. AB - Computer assisted detection systems (CAD) in mammography incorporate two critical stages: (i) prescreening to localize suspicious regions and (ii) detailed analysis of the regions for false positive reduction. In this work, we present a new technique for automatic detection of suspicious masses for prescreening mammograms. The hypothesis of the proposed technique is that malignant masses manifestate as superimposed concentric layers. Morphological characterization of these layers can form the foundation of an automated scheme for detection of suspicious masses. The study was based on fifty nine screening mammograms from the digital database of screening mammography (DDSM). Overall, the proposed scheme performs at 85.7% sensitivity with an average of 0.53 false positives per image. The scheme targets malignant masses and, thus it can provide a second opinion to radiologists without sending benign masses to unnecessary biopsy. PMID- 17271924 TI - Feasibility of transmission microCT with two fan-beam sources. AB - We study in simulation the properties of a transmission CT system using two fan beam sources both illuminating a single detector. Using traditional X-ray sources, such a system would be expensive, slow, and unwieldy. With the development of new X-ray sources based on nanofabrication methods, however, such a dual-source system becomes feasible. The principal advantage of the new geometry is that a shorter fan-beam (or cone-beam) focal length can be used while achieving the same field-of-view. The shorter focal length should achieve approximately the same spatial resolution since the magnification is offset by the increased effect of nonzero focal spot size. However, the shorter focal length should give better efficiency through inverse square law effects. A disadvantage is that analytical reconstruction methods based on filtered backprojection may not be effective since each source does not view the entire subject. We demonstrate that iterative reconstruction techniques can solve this problem. We also demonstrate the potential improvement in resolution for an ideal source using a microCT simulation by comparing a conventional single source fan beam CT with 50 cm focal length to a dual-source system with 30.5 cm focal length, both giving approximately the same transverse field of view. We found that the ideal dual-source system improved transverse spatial resolution (FWHM) by 4-14%, although wider tails (FWTM) were noted in point spread estimates. We conclude that use of multiple fan-beam sources is feasible to create transmission CT devices with shorter focal lengths. PMID- 17271925 TI - Conductivity images of biological tissue phantoms using a 3.0 tesla MREIT system. AB - We present cross-sectional conductivity images of a biological tissue phantom obtained by using a 3.0 Tesla magnetic resonance electrical impedance tomography (MREIT) system. Inside the cylindrical phantom with 140 mm diameter and 140 mm height, biological tissues such as bovine tongue and liver, porcine muscle, and chicken breast were placed within an agar gelatin. Injecting current of 480 mA.ms into the tissue phantom, we measured the z-component B/sub z/ of the induced magnetic flux density B=(B/sub x/, B/sub y/, B/sub z/). Using the harmonic B/sub z/ algorithm, we reconstructed cross-sectional conductivity images from the measured B/sub z/ data. Reconstructed images clearly distinguish different tissues in terms of both their shapes and conductivity values. PMID- 17271926 TI - A correction method for nonlinear artifacts in CT imaging. AB - This work presents a new method to reduce nonlinear artifacts in computed tomography (CT). Based on the traditional water-equivalent beam hardening correction method, a new systematic iterative algorithm has been designed to modify the original spectrum, which is under the influences of certain added filter materials and some unknown factors. By incorporating the characters of polychromatic beam hardening and the insensibility and nonuniformity of detectors into consideration, a new polynomial function curve is calculated. The curve can calibrate CT raw data and reduce the nonlinear artifacts, such as shading artifacts, dark artifacts, cupping artifacts and ring artifacts, in soft tissue. Comparing with the traditional water-equivalent correction, results show that this method can significantly improve the image quality. Meanwhile, the method is pre-processing and will not increase the normal reconstruction time. That is, all the time-consuming works can be done before scanning patients. However, it is still depending on the size of phantoms currently used, and more detailed works need to be done in the future. PMID- 17271927 TI - Three-dimensional visualization of intact mouse lung by synchrotron radiation CT. AB - Airway is a complex branching structure of many compliant tubes, and then airway geometry and compliance have many biomechanical and clinical implications. In this study, we visualized an intact mouse lung without dehydration and fixation using synchrotron radiation CT at SPring-8 in Japan. The CT system consists of X ray light source, a double crystal monochromator, a rotation stage and a high resolution image detector. The angular projections were sequentially obtained during the sample rotation with the total scan shorter time than 15 min. The effective spatial resolution was 30 mum. Using this system, three-dimensional images of small airways and alveoli were obtained under physiological condition. Moreover, we visualized the same airways at FRC (functional residual capacity) and TLC (total lung capacity). The airway geometry deformed dramatically and the diameter expanded 1.2-1.7 times at TLC in comparison with at FRC. This deformation was larger for smaller airways. This system opens the way to new research of the pulmonary dynamics and physiological implications. PMID- 17271928 TI - Similarity searching for chest CT images based on object features and spatial relation maps. AB - In this paper, an object-based image retrieval system for chest CT image databases is proposed. Based on the scheme of the content-based image retrieval method, we proposed an image segmentation method which combines the anatomical knowledge of the chest and the well-known watershed segmentation algorithm. The purpose of segmentation is to identify the mediastinum and the two lung lobes in a chest CT image. The ARGs (attributed relational graphs) are chosen to describe the features of segmented objects. Then, image database is constructed by the feature vectors of images. In database searching, two searching modes are provided that are "query by example" and "query by object". Our system uses Euclidean distance to measure the similarity between the image in query and the image in database. The system output the 30 most similar images in the chest CT image database as query results. The experimental results show that the average precision of our system is about 80% which is impressive in a totally automatic medical image retrieval system. Moreover, query concentrated in certain objects features usually show better result than the regular query by example. The possible reasons are discussed. PMID- 17271929 TI - Medical applications of terahertz imaging: a review of current technology and potential applications in biomedical engineering. AB - Terahertz (THz) imaging is in its early stages of development but already the potential clinical impact of this new imaging modality is clear. From cancer research to DNA analysis THz technology is improving or even making possible imaging of hitherto inaccessible phenomena. In this paper we present a short review of THz imaging from the point of view of biomedical engineering. We discuss the current state of the art in terms of THz imaging systems; describe current applications, future potential and our own approaches to harnessing this novel technology. We draw attention to open problems in the area with respect to the limitations of the technology before concluding with descriptions of our future work in the area. PMID- 17271930 TI - Noncontact scanning electrical impedance imaging. AB - We are interested in applying electrical impedance imaging to a single cell because it has potential to reveal both cell anatomy and cell function. Unfortunately, classic impedance imaging techniques are not applicable to this small scale measurement due to their low resolution. In this paper, a different method of impedance imaging is developed based on a noncontact scanning system. In this system, the imaging sample is immersed in an aqueous solution allowing for the use of various probe designs. Among those designs, we discuss a novel shield-probe design that has the advantage of better signal-to-noise ratio with higher resolution compared to other probes. Images showing the magnitude of current for each scanned point were obtained using this configuration. A low frequency linear physical model helps to relate the current to the conductivity at each point. Line-scan data of high impedance contrast structures can be shown to be a good fit to this model. The first two-dimensional impedance image of biological tissues generated by this technique is shown with resolution on the order of 100 mum. The image reveals details not present in the optical image. PMID- 17271931 TI - Non-contact scanning electrical impedance imaging. AB - We are interested in applying electrical impedance imaging to a single cell because it has potential to reveal both cell anatomy and cell function. Unfortunately, classic impedance imaging techniques are not applicable to this small scale measurement due to their low resolution. In this paper, a different method of impedance imaging is developed based on a non-contact scanning system. In this system, the imaging sample is immersed in an aqueous solution allowing for the use of various probe designs. Among those designs, we discuss a novel shield-probe design that has the advantage of better signal-to-noise ratio with higher resolution compared to other probes. Images showing the magnitude of current for each scanned point were obtained using this configuration. A low frequency linear physical model helps to relate the current to the conductivity at each point. Line-scan data of high impedance contrast structures can be shown to be a good fit to this model. The first two-dimensional impedance image of biological tissues generated by this technique is shown with resolution on the order of 100 mum. The image reveals details not present in the optical image. PMID- 17271932 TI - A simplified model of mammography geometry for breast cancer imaging with electrical impedance tomography. AB - One recent application area of EIT is the detection of breast cancer by imaging the conductivity and the permittivity distribution inside the breast. The present "gold standard" for breast cancer detection is X-ray mammography, and it is desirable that the EIT and the X-ray mammography use the same geometry. This work presents a simplified model of the mammography geometry for EIT imaging. The mammography geometry is modeled as a rectangular box with electrode arrays on the top and bottom planes. A forward model for the electrical impedance imaging problem is derived for the homogeneous conductivity distribution and validated by experiment using a phantom tank. The effect of unmodeled surface on the sides of the electrodes is studied. PMID- 17271933 TI - Comparison of fibroglandular tissue distributions for microwave tomographic breast images with complementary MR T2 weighted images. AB - We have recently demonstrated good correlation between the recovered permittivity from microwave imaging (MIS) and the recovered water content from near infrared imaging (NIR) for a common set of normal patients undergoing associated breast examinations. We have subsequently conducted a small sample of comparison breast examinations between microwave imaging and MR to assess possible correlation between the location and extent of the fibroglandular as seen on MR images with increased permittivity zones of the microwave images. From various physiological and MR breast studies, it has been shown that the fibroglandular regions are generally comprised of significantly higher levels of water than the more dominant adipose tissue. The initial results of this study are quite encouraging and demonstrate obvious correlations between the permittivity and MR-recovered fibroglandular regions for a set of patients with widely varying tissue type variations. In addition, they illustrate the value of extracting diagnostic information from multiple modalities especially where the amount of direct in vivo property measurements is limited or nonexistent. PMID- 17271934 TI - Subsecond observations of EIT voltage changes on the human scalp due to brain stimulus. AB - A pilot study has investigated the feasibility of imaging human brain function using an electrical impedance tomography (EIT) system time-locked to an evoked response (ER) system. A sixteen-electrode planar EIT configuration was used with polar current injection. We report here measurements on two volunteer patients who were fully awake in all tests. Reference data (with no applied stimulus) yield EIT nearest-neighbour voltage differences over the range 5-28 mV. In comparison with forward calculations [C.M. Towers et al. (2000)], these data suggest a value of skull conductivity of the order of 0.05 S/m. Visual and auditory stimuli were applied as single discrete events to evoke neural responses (VER and AER respectively). In each case, EIT data acquisition commenced at a time between 70 and 740 ms later, taking 308 ms to complete. Average values of voltage pair data over many frames are presented here, with the emphasis on the VER data. When comparing data taken under stimulus conditions against the reference data, voltage differences of up to approximately 3 mV are observed in both AER and VER cases. We attribute these voltage changes to synaptic activity. Preliminary reconstructed images of conductivity are discussed. PMID- 17271935 TI - A new approach to current density impedance imaging. AB - Current density impedance imaging (CDII) is a new impedance imaging technique that utilizes current density vector measurements made using magnetic resonance imager (MRI). CDII provides a simple mathematical expression for the gradient of the logarithm of conductivity, nablaln(sigma), at each point in a region where two current density vector has been measured. From the images of the gradient of the logarithm of conductivity, ln(sigma) can be reconstructed through integration and of sigma by a priori knowledge of the conductivity at a single point in the object. The CDII technique was tested on a conductivity phantom made from tissue mimicking gel. The results showed accurate reconstruction of the gel conductivity from two current density measurements. This study, for the first time, has demonstrated a local reconstruction technique to calculate sample conductivity inside the phantom noninvasively. PMID- 17271936 TI - Ultrasonic techniques for assessing wall vibrations in stenosed arteries. AB - Arterial stenoses are often associated with audible bruits. Quantitative analysis of the bruit spectrum has been successfully used to predict the residual lumen diameter in carotid stenoses. Arterial wall vibrations occurring due to turbulent pressure fluctuations in the post-stenotic jet are known to be the source of the bruits. We present novel signal processing techniques that enable the detailed noninvasive assessment of these vibrations in real time using color-Doppler and pulsed-wave Doppler ultrasound. A color-Doppler-based two-dimensional vibration imaging technique can be used to locate the source of the bruits relative to the underlying anatomy. Subsequently, a pulsed-wave Doppler-based technique can be used to analyze the bruit spectrum quantitatively. Experiments in ex vivo arteries indicate that these techniques can predict the location of the bruit as well as its spectral content. Case studies on human subjects with stenosed vein grafts are presented and the clinical applicability of this technique is discussed. PMID- 17271937 TI - Attenuation mapping for monitoring thermal therapy using ultrasound transmission imaging. AB - The use of an ultrasound (US) transmission imaging system to monitor attenuation changes during tissue heating was investigated. This work presents preliminary results of images obtained from an acoustic camera before, during and after heating tissue phantoms using a heated needle. Two types of tissue-mimicking phantoms were used, agar and polyacrylamide-based. Regions of interests were chosen in images obtained from the real-time imaging system, and the pixel intensity values before, during and after heating were compared. In both phantoms, a decrease in image intensities was observed during heating, indicating an increase in tissue attenuation. Additionally, an irreversible change in image intensity was observed in regions close to the heat source. The reversibility of the intensity change was shown to be a function of the distance from the heating needle to the selected region. Initial results indicate that US transmission imaging can be used to monitor thermal therapy. PMID- 17271938 TI - Implementation of a system using reflective tomographic reconstruction for breast cancer detection. AB - The following describes the implementation of a system for ultrasonic mammography. The system employs adaptive imaging and processing techniques to produce high-resolution breast tissues sonograms. The time-domain imaging technique provides quantitative maps of intrinsic acoustic tissue properties using conventional pulse-echo transducers and clinical scanning system. The increased image resolution and quantitative maps provide improve diagnostics tools compared with conventional B-scan images. PMID- 17271939 TI - New adaptive clutter rejection based on spectral analysis in ultrasound color flow imaging. AB - We have developed a new adaptive clutter rejection technique where an optimum clutter filter is dynamically selected according to the varying clutter characteristics in ultrasound color-flow imaging. The selection criteria have been established based on spectral analysis of an estimate of the temporal autocorrelation matrix of clutter signals. The performance of the clutter rejection techniques is quantified from a wall-less flow phantom and in vivo studies. The in vivo color-flow images obtained from hepatic veins are presented to illustrate the potential of the proposed adaptive clutter rejection technique. In hepatic vein in vivo studies, we obtained an average gain of 4.1 dB and 3.4 dB in flow signal-to-clutter-ratio compared to the conventional and down-mixing methods, respectively. PMID- 17271940 TI - Measurement of ultrasound speed of articular cartilage in variable conditions. AB - Ultrasound (US) imaging and measurement have been widely used for the assessment of articular cartilage (AC) in recent years. Assessment involved the measurement of acoustic properties such as US speed in AC. Those measurements were normally carried out either at room temperature or at 37 degrees C and at 0.15 M saline concentrations. The changes in the structure of AC due to the change in the concentration of bathing saline solution have been previously reported. However, the change in the US speed of AC has not been yet documented. In addition, the variation of temperature during measurements may affect the US speed in AC. The objective of this study is to investigate the change of the US speed in AC with the variations in temperature and the bathing saline concentration. Results demonstrated that the US speed significantly increased with the increase of temperature (15 degrees C to 40 degrees C) and saline concentration (0 M to 2.5 M). PMID- 17271941 TI - Direct phase-based strain estimator for ultrasound tissue elasticity imaging. AB - Palpation has been widely used to detect hard tumorous tissues surrounded by softer normal tissues. The goal of ultrasound tissue elasticity imaging is to extract information regarding tissue stiffness that is closely related to pathology. For this tissue elasticity imaging, compression is applied first, and the amount of resulting tissue deformation or strain needs to be estimated. Traditionally, strain estimators aim to accurately derive tissue displacements between pre- and post-compression and compute strain from the displacements. However, the displacement can be as large as a thousand times of strain for typical compression levels used in ultrasound elasticity imaging. Error in displacement estimation leads to a large variance in strain, thus resulting in poor signal to noise ratio for the estimated strain. We have developed a novel strain estimator that directly estimates strain from the phase of temporal and spatial correlation instead of estimating small strain from large displacements. SNRe (signal to noise ratio of elastogram) and CNRe (contrast to noise ratio of elastogram) using the direct strain estimator are at least three times and six times larger than that using conventional displacement-based strain estimators, respectively. These results indicate that the direct strain estimator can significantly improve accuracy and lesion detectability in ultrasound elasticity imaging. In addition, the direct strain estimator is computationally efficient compared to conventional estimators, thus enabling the realtime implementation and clinical use of this new ultrasound imaging mode. PMID- 17271942 TI - Geometrical importance sampling and pulse height tallies in GATE. AB - Monte Carlo simulations are widely used to study the behavior and detection of gamma photons in medical imaging devices. Such simulations are computationally expensive. This is why geometrical importance sampling, a variance reduction technique, was recently incorporated into the GEANT4 Monte Carlo code. In order to use this technique for single photon emission computed tomography (SPECT) imaging, it needed to be made compatible with pulse height tallies. These tallies correspond to the number of detected pulses in distinct energy bins, covering an energy spectrum relevant to SPECT. Since each pulse is the combination of different detector hits, the tally bin is not known until the end of an event. In an analog simulation (without variance reduction) this poses no problems as each detected hit can be stored and the pulse can be calculated at the end of each event. Geometrical importance sampling combined with Russian Roulette however introduces branches into the particle history, which results in a much more complicated pulse calculation. This work describes how pulse height tallies are adjusted to geometrical importance sampling and Russian Roulette within GATE, a medical imaging and simulation application based on GEANT4. The validation of this technique is done through SPECT simulations comparing the analog result with the new method. PMID- 17271943 TI - Improved SAGE algorithm for PET image reconstruction using rescaled block iterative method. AB - Iterative reconstruction methods such as the expectation maximization maximum likelihood (EMML) method can be accelerated by using a rescaled block-iterative (RBI) algorithm. It was demonstrated that the space-alternating generalized expectation-maximization (SAGE) algorithm is superior to the EMML due to the following facts: (1) The hidden data spaces can be appropriately chosen and then be used in SAGE algorithm to speed up the convergence rate. (2) SAGE algorithm updates the parameters sequentially which makes its M-step to be treated more easily. In this paper, we present a novel algorithm that combines the RBI algorithm with SAGE algorithm. The convergence property of RBI-SAGE is discussed, and the image quality is assessed with mean absolute error and chi-square error. The experimental results show that the proposed method is more effective than the SAGE algorithm even if the projection data includes statistic noise. PMID- 17271944 TI - Optimization of a PET scanner design for prostate lesion detection. AB - The recent development of new prostate tracers has motivated us to build a low cost PET camera optimized to image the prostate. Coincidence imaging of positron emitters is achieved using a pair of curved detector banks. In this paper, we optimize the design of septa in the prostate camera for detecting prostate tumors. The performance of the system is measured using a prewhitening observer with a background-known-statistically task. The results show that the septa design has a large impact on lesion detection. At the background activity level of 0.1 muCi/cc, a novel septa design with 8-crystal spacing outperforms the traditional two-dimension (interplane septa) and three-dimension (septa-less) designs. PMID- 17271945 TI - Maximum likelihood algorithm for PET image reconstruction based on fuzzy random variable. AB - This work presents a new iterative method for reconstructing positron emission tomography (PET) images. Unlike conventional maximum likelihood-expectation maximization (MLEM), this method intends to introduce the fuzzy set principle to MLEM algorithm. In this work, the noncognitive uncertainty of the observed projection data are described by their probability density function; whereas the cognitive uncertainty of a random variable can be described by the membership function for its fuzziness. The mean of the observed projection data are regard as fuzzy random variables because of the complexity of system. The fuzzy random variable can be represented by a triangular membership function. We establish a joint probability density function that includes the effects of both fuzziness and randomness. The maximum likelihood approach is used to estimate the image vector. The order subset (OS), rescaled block-iterative (RBI), and row-action (RA) techniques are applied to our PET reconstructed method to speed up the convergence rate and to decrease the iteration numbers. PMID- 17271946 TI - Applying 2D ML iterative reconstruction methods with resolution recovery to 3D PET data: evaluation of rebinning effects. AB - The applicability of OSEM reconstruction algorithms with space dependent resolution recovery to clinical FDG-PET studies is verified. The performance of the 2D algorithm is improved by means of a low resolution initialization and by a infra-iteration Metz filtering. Effects of different rebinning algorithms on 3D data are assessed, concluding that they do not alter the transaxial plane blurring parameters, thus permitting a straightforward application of 2D OSEM reconstruction after rebinning, with the same system matrix. Finally axial degradation was also quantified, finding that FORE is the best rebinning method to be combined with the 2D OSEM reconstruction. PMID- 17271947 TI - Sensitivity analysis for magnetic induction tomography. AB - This work focuses on sensitivity analysis of magnetic induction tomography in terms of theoretical modelling and numerical implementation. We will explain a new and efficient method to determine the Jacobian matrix, directly from the results of the forward solution. The results presented are for the eddy current approximation, and are given in terms of magnetic vector potential, which is computationally convenient, and which may be extracted directly from the FE solution of the forward problem. Examples of sensitivity maps for an opposite sensor geometry are also shown. PMID- 17271948 TI - Novel methods of time-resolved fluorescence data analysis for in-vivo tissue characterization: application to atherosclerosis. AB - This study investigates the ability of new analytical methods of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data to characterize tissue in vivo, such as the composition of atherosclerotic vulnerable plaques. A total of 73 TR-LIFS measurements were taken in-vivo from the aorta of 8 rabbits, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified as normal aorta, thin or thick lesions, and lesions rich in either collagen or macrophages/foam-cells. Different linear and nonlinear classification algorithms (linear discriminant analysis, stepwise linear discriminant analysis, principal component analysis, and feedforward neural networks) were developed using spectral and TR features (ratios of intensity values and Laguerre expansion coefficients, respectively). Normal intima and thin lesions were discriminated from thick lesions (sensitivity >90%, specificity 100%) using only spectral features. However, both spectral and time resolved features were necessary to discriminate thick lesions rich in collagen from thick lesions rich in foam cells (sensitivity >85%, specificity >93%), and thin lesions rich in foam cells from normal aorta and thin lesions rich in collagen (sensitivity >85%, specificity >94%). Based on these findings, we believe that TR-LIFS information derived from the Laguerre expansion coefficients can provide a valuable additional dimension for in-vivo tissue characterization. PMID- 17271949 TI - A new system for the assessment of diabetic foot planter pressure. AB - Most skin injuries in neuropathy-type diabetic foot patients occur on the planter soft tissue at sites of abnormally high pressure values. If not detected and treated early enough, these localized sites are likely to develop skin breakdown and ulceration, which puts the patient at higher risks including the need for amputation. Current diagnostic techniques, such as CT and MRI, are primarily used for assessing later stage patients but are not used for screening. In this work, we report a new system for the assessment of planter pressure distribution. The system is easy to use, inexpensive, and may provide the needed accuracy to become a screening and ulceration risk assessment device. The method used is based on the "blanching" effect of tissue that occurs when it is under pressure. Using a standard optical scanner, we acquire the footprint under body weight and map the resulting blanching to different intensity levels. Different intensity levels are mapped to different color codes to obtain pressure distribution maps. These maps can be used by the clinician to identify high risk sites to help prescribe the necessary intervention. Initial testing of the system has demonstrated encouraging preliminary results. PMID- 17271950 TI - Two-dimensional autocorrelation method for ultrasound-based strain estimation. AB - Ultrasound strain imaging maps the tissue stiffness in the region of interest by estimating strain when the tissue is stressed. Prestress and poststress ultrasound echoes are processed to estimate the displacements, and the strain image is computed by a spatial derivative of the estimated displacement. Due to the nature of derivative operations, smaller errors in displacement estimation can cause large noise in the computed strain image. When tissue displacements are estimated using the phase of the autocorrelation between the prestress and poststress data (i.e., 1D autocorrelation method), it has been previously reported that local variations in ultrasonic center frequency due to speckle can introduce errors in the estimated displacement. We have developed a new method to compute strain based on two-dimensional autocorrelation. By estimating the local ultrasound frequency, we can improve the accuracy of displacement estimates and hence reduce the noise in strain images. We have analyzed the effect of local frequency changes on noise in strain images and the improvement in the strain signal-to-noise ratio with the 2D autocorrelation method. The simulation results are supported by experiments with homogenous gelatin phantoms and show that strain signal-to-noise ratio with 2D autocorrelation is consistently higher than that with 1D autocorrelation. The 2D autocorrelation can increase the strain signal-to-noise ratio by up to 200%, which leads us to believe that our estimation method can significantly improve the quality of strain images. PMID- 17271951 TI - A three dimensional inverse scattering algorithm in the time-domain based on nonlinear optimization. AB - A new algorithm for solving the three-dimensional inverse scattering problem using time-domain data is presented. The algorithm is intended for application in cases where linearization using the Born or Rytov approximations is not possible. A functional is defined accounting for the error of the object and data equations and the unknown coefficients of the internal field and the object function are sought in order to minimize it. The algorithm projects the unknown internal field into a space of Gaussian basis functions aiming to decrease the number of the unknown coefficients. Time-windowing is utilized in order to reduce the size of the optimization problem. PMID- 17271952 TI - New protocol for leg ulcer tissue classification from colour images. AB - Measurement of wound healing status is very important for monitoring progress in individual patients. Tissue classification is a vital step in the development of an automatic measurement system for wound healing assessment. We present a new tissue classification protocol using the RGB (Red, Green and Blue) histogram distributions of pixel values from wound color images. These three histogram distributions (extracted features) were used as three two-dimensional (2D) input signals for classification. This protocol has been carried out using the KNN classifier and results show that the proposed protocol provides an extremely competent practical method for the classification of wound tissues. PMID- 17271953 TI - Precision control of eluted activity from a Sr/Rb generator for cardiac positron emission tomography. AB - A rubidium-82 (/sup 82/Rb) elution system is described for use with clinical positron emission tomography. The system is self-calibrating with 1.4% repeatability, independent of generator activity and elution flow rate. Saline flow is switched between a /sup 82/Sr//sup 82/Rb generator and a bypass line to achieve a constant activity elution of /sup 82/Rb. In the present study, pulse width modulation (PWM) of a solenoid valve is compared to simple threshold control as a means to simulate a proportional valve. A predictive-corrective control algorithm is developed which produces a constant activity elution within the constraints of long feedback delay and short elution time. Accurate constant activity elutions of 10-70% of the total generator activity were demonstrated using the threshold comparison control. The adaptive-corrective control of the PWM valve provided a substantial improvement in precision of the steady-state output. PMID- 17271954 TI - Computer-aided diagnosis of solid breast nodules on ultrasound with digital image processing and artificial neural network. AB - A computer-aided diagnosis algorithm identifying breast nodule malignancy using multiple ultrasonography features and artificial neural network classifier was developed from a database of 584 histologically-confirmed cases containing 300 benign and 284 malignant breast nodules. The features were extracted from sonographic images through digital image processing. An artificial neural network then distinguished malignant nodules based on those features. The trained artificial neural network showed the normalized area under the receiver operating characteristic curve of 0.95. PMID- 17271955 TI - Quantification of coronary flow velocity reserve by means of semiautomated analysis of coronary flow Doppler images. AB - Coronary flow reserve (CFVR) is conventionally obtained by manual tracings of Doppler profiles, as ratio of control vs stress diastolic peak velocity. This parameter could help in discriminating between normal (N) and microcirculatory pathologic (P) subjects, even the clinical meaning of 1.93) and 15 P (CFVR<1.8) subjects, to assess whose of the new parameters could be able to discriminate between these groups. Results indicated that many of the new parameters were able to evidence significant differences between N and P, thus representing new clinical indices useful for the diagnosis. PMID- 17271956 TI - Atherosclerotic carotid plaque segmentation. AB - Atherosclerosis is the major cause of heart attack and stroke in the western world. In this paper we present a computerized method for segmenting the athrerosclerotic carotid plaque from ultrasound images. The method uses the blood flow image first to detect the initial contour of the plaque, and then despeckle filtering and snakes to deform the initial contour for best fit of plaque boundaries. The accuracy and reproducibility of this method was tested using 35 longitudinal ultrasound images of carotid arteries and the results were compared with the manual delineations of an expert. The comparison showed that the computerized method gives satisfactory results with no manual correction needed in most of the cases. The true positive fraction, TPF, true negative fraction, TNF, false negative fraction, FNF and false positive fraction, FPF, were 86.44%, 84.03%, 8.5%, and 7% respectively. PMID- 17271957 TI - Characterization of carotid atherosclerosis based on motion and texture features and clustering using fuzzy c-means. AB - Analysis of B-mode ultrasound images of the carotid atheromatous plaque includes the estimation of texture from static images and the estimation of motion from image sequences. The combination of these two types of information may be valuable for accurate diagnosis of vascular disease. The purpose of this paper was to study texture and motion patterns of carotid atherosclerosis and select the optimal combination of features that can characterize plaque. B-mode ultrasound images of 10 symptomatic and 9 asymptomatic plaques were interrogated. A total of 99 texture features were estimated using first-order statistics, second-order statistics, Laws texture energy and the fractal dimension. Only five texture features were significantly different between the two groups. In the same subjects, the motion of selected plaque regions was estimated using region tracking and block-matching and expressed through: a/maximal surface velocity (MSV), and b/maximal relative surface velocity (MRSV). MSV and MRSV were significantly lower in asymptomatic plaques suggesting more homogeneous motion patterns. Clustering using fuzzy c-means correctly classified 74% of plaques based on texture features only, and 79% of plaques based on motion features only. Classification performance reached 84% when a combination of motion and texture features was used. PMID- 17271958 TI - Estimation of ultrasound attenuation coefficient using log-spectrum domain processing. AB - Ultrasound attenuation coefficient is an important diagnostic parameter in medical ultrasonography. Furthermore, it is a parameter of a component related to the attenuation process of the space-variant point spread function, which can be used to improve the spatial resolution of ultrasound images through deconvolution. A recently published approach to the estimation of the ultrasound attenuation coefficient from B-scan radiofrequency data is extended and explained in a detail. First, a parametric image of the mean attenuation coefficients between the probe and a given pixel position is computed by applying linear regression to log-spectra of short segments of radiofrequency signals. Three methods of forming the parametric image are presented. As a second step, the local tissue-specific attenuation coefficients are estimated in small regions of the obtained parametric image. The method has been tested on synthetic radiofrequency data and on radiofrequency data recorded from a tissue-mimicking phantom. A fairly good correlation with the known reference values was achieved. PMID- 17271959 TI - The integration of medical imaging and computational fluid dynamics for measuring wall shear stress in carotid arteries. AB - The link between atherosclerosis and wall shear stress (WSS) has lead to considerable interest in the in vivo estimation of WSS. Both magnetic resonance imaging (MRI) and three-dimensional ultrasound (3DUS) are capable of providing the anatomical and flow data required for subject-specific computational fluid dynamics (CFD) simulations. This study compares, for the first time, predicted 3D flow patterns based on black blood MRI and 3DUS. Velocity fields in the carotid arteries of nine subjects have been reconstructed, and the haemodynamic wall parameters WSS, oscillatory shear index (OSI), WSS gradients (WSSG) and angle gradients (WSSAG) were computed and compared. There was a good qualitative agreement between results derived from MRI and 3DUS, embodied by a strong linear correlation between the patched representations of the haemodynamic wall parameters. The root-mean-square error between haemodynamic wall parameters was comparable to the range of the expected variability of each imaging technique (WSS: 0.411 N/m; OSI: 0.048; temporal WSSG: 2.29 N/(s.m/sup 2/); spatial WSSG: 150 N/m/sup 3/; WSSAG: 87.6 rad/m). In conclusion, MRI and 3DUS are comparable techniques for combining with CFD in the carotid artery. The relatively high cost of MRI favour 3DUS to MRI for future haemodynamic studies of superficial arteries. PMID- 17271960 TI - 2-D CVIB imaging in animal experiments. AB - To demonstrate the feasibility and validity of 2-D CVIB (Cyclic variation of Integrated Backscatter) imaging method, animal experiments were conducted. Among 10 anesthetized open-chest dogs, acute myocardial ischemia was induced by occluding left anterior descending coronary artery. While scanning normal hearts and ischemic hearts with the ultrasonic B scanner, digital radiofrequency data were acquired by a real-time acquisition system in synchronism. The offline analysis to the radio-frequency signal with the 2-D CVIB imaging method was performed to verify the consistency between the imaging results and the design of the experiments. The experimental results showed that the 2-D CVIB imaging method was successful in detecting the ischemic myocardium and might provide a new noninvasive way for the cardiologists to both quantitatively and visually evaluate the contractile performance of the myocardium. PMID- 17271961 TI - 3-D microwave imaging of breast tumors with matched-filtering. AB - Matched-filtering is applied to an algorithm similar to confocal microwave imaging of the breast in order to better detect tumors in a 3-D FDTD model. Strongly scattering objects detected by the imaging algorithm are examined for tumor existence through matched-filtering. Based on the matched-filtering examination, early-time clutter is well suppressed by this method. Also, an antenna-array with a spatial resolution of 8.3 mm is shown to be effective in reducing the clutter level for the successful detection of a 5-mm-diameter spherical tumor. PMID- 17271962 TI - Imaging capability of an early stage breast tumor by CP-MCT. AB - Capability of diagnostic imaging of an early stage breast tumor using microwaves has been investigated by means of FDTD-based numerical simulations. More than ten years ago, we developed chirp pulse microwave computed tomography (CP-MCT) for microwave imaging of a human body. In this study, we'll show that CP-MCT provides useful information on the tumor region in the breast. To specify the exact location of an early stage tumor inside the breast, image restoration has been attempted by computing the point spread function (PSF) of CP-MCT in two- or three dimensional ways by assuming the function is linear. Another solution is given by using radar imaging system simultaneously with CP-MCT. PMID- 17271963 TI - WKB quasistatic reconstruction of layered biological tissues. AB - A novel electrical impedance tomography method is introduced for reconstruction of layered biological tissues. The method utilizes a recently proposed image series expansion scheme in conjunction with the WKB approximation. This results in a locality feature, assigning analytically to each image term a local impedance associated with a unique layer, and thus leading to efficient and accurate reconstruction procedures. PMID- 17271964 TI - A reconstruction algorithm based on wavelet network in electrical impedance tomography. AB - Electrical impedance tomography (EIT) is a noninvasive technique to estimate the conductivity distribution inside the object. In EIT, driving currents are injected through the object and voltages are measured at the electrodes on the surface. Algorithms to estimate the conductivity distribution from the measured voltages are called reconstruction algorithms. Image reconstruction is a nonlinear inverse problem and typically ill-conditioned. Some algorithms for image reconstruction including equal-potential back-projection, regularization, and sensitivity matrix, modified Newton-Raphson methods have been proposed in past, all of these techniques, while giving reasonable solutions, require simplifying hypotheses about the problem. This paper presents a new reconstruction algorithm based on wavelet network, which calculates conductivity distribution directly from finite-element simulations of forward problem. To indicate the validity of this method, we have gotten the conductivity distribution for the three-concentric-shell spherical head model using this algorithm, the result show it is speed of image reconstruction, conceptual and ease of implementation. PMID- 17271965 TI - A concept for hip prosthesis identification using ultra wideband radar. AB - Ultra wideband (UWB) radar has been extensively investigated both theoretically and practically for the identification buried artifacts. Ground probe radar (GPR) concentrates on the identification of lightly buried land mines, unexploded ordnance (UXO) and archeological targets. The same technology is proposed in a similar context for the rapid identification of in vivo implanted metallic prostheses. The technique is based on resonance based target identification and the paper investigates UWB scattering from a metallic hip prosthesis in free space as a first step in the identification process. PMID- 17271966 TI - Fractal analysis of replication site images of the human cell nucleus. AB - Epi-fluorescent microscopic images of the mammalian cell nucleus taken during the early, mid and late S (synthetic) phase of the cell cycle suggest that the mass of replicating DNA that belong to the cell nucleus can be characterized as a space filling fractal curve. We reason from a biological standpoint and our understanding of naturally occurring fractals that our microscopic images reveal portions of the spatially complex DNA molecule and present methods for computing the fractal dimensions of the images. Results presented here suggest that our methodology based on fractal properties can distinguish replication of DNA occurring in early versus mid or late S-phase. PMID- 17271967 TI - Quantifying motion in video recordings of neonatal seizures by feature trackers based on predictive block matching. AB - This work introduces predictive block matching, a method developed to track motion in video by exploiting the advantages of block motion estimation and adaptive block matching. The proposed method relies on a pure translation motion model to estimate the displacement of a block between two successive video frames before initiating the search for the best match of the block tracked throughout the frame sequence. The search for the best match relies on adaptive block matching, which employs an update strategy based on Kalman filtering to account for the changing appearance of the block. Predictive block matching was used to extract motor activity signals from video recordings of neonatal seizures. PMID- 17271968 TI - A method for size estimation of amorphous pupil in 3-dimensional geometry. AB - Measuring pupil size is a noninvasive method for evaluation of autonomic nervous system (ANS) activity because the pupil is exclusively controlled by the autonomic nervous system. To evaluate the activity of ANS, an accurate pupil size calculation method different from those of pupillometer and eye tracker should be suggested. This paper presents a three-dimensional model of eye and pupil and also suggests an accurate estimation method of pupil size from images projected on two-dimensional image plane with distortions. PMID- 17271969 TI - Zernike moment invariants based photo-identification using Fisher discriminant model. AB - This paper presents a photo-identification algorithm using Zernike moment invariants embedded in a subspace optimal for pattern identification. Fisher discriminants are used and the invariants are projected onto the subspace spanned by the Fisher basis vectors. The technique has been applied to photo identification of gray whales (Eschrichtius robustus) using their field images. White patches (blotches) appearing on a gray whale's left and right flukes constitute unique identifying features and have been used here for individual identification. The fluke area is extracted from a fluke image via the live-wire edge detection algorithm, followed by optimal thresholding of the fluke area to obtain the blotches. Zernike moment invariants are then calculated for the blotches and projected onto the subspace spanned by Fisher basis vectors. These invariants are used as the feature vector representing a database image. During matching, the database images are ranked depending on the degree of similarity between a query and database feature vectors. The results show that the use of this algorithm leads to a significant reduction in the amount of manual search that is normally done by marine biologists. PMID- 17271970 TI - Pattern classification of nevus with texture analysis. AB - The purpose of this research is to classify the pattern on the surface of the nevus. The digital image that contains one nevus is classified into three kinds of patterns of homogeneous pattern, globular pattern, and reticular pattern by the texture analysis. The tumor part in the image is specified first, and the specified tumor part is divided into some sub-images. Afterwards, the amount of the texture features of each sub-image was calculated. The pattern was classified by the discriminant analysis based on the amount of the texture features. As a result, the patterns could be classified correctly into three categories at the ratio of 94%. PMID- 17271971 TI - The evaluation of facial palsy by amount of feature point movements at facial expressions. AB - At present, in the medical field 40-point method and facial nerve grading system are generally used for evaluation of facial palsy. However, these methods have limitation in the precise evaluation, because of subjectivity in diagnosis. Purpose of This work is to propose quantitative evaluation of facial palsy based on the amount of movements of the feature point on the face. Facial nerve symptoms generally appear in either side of the face. In facial expression movement, the motion in the palsy side becomes smaller than that of the healthy side. We defined some indices of palsy grade obtained by the observation of the facial motion. Those indices showed the asymmetry of the facial motion quantitatively. We confirmed that our proposed method is valid for estimation of facial palsy from comparison with 40 points method. PMID- 17271972 TI - Monte Carlo image reconstruction of a mammographic phantom. AB - The aim of this study is the development of a methodology to reconstruct via Monte Carlo techniques the radiographic image of the CIRS 11 A (MAMMO PHANTOM SP01) phantom. This phantom is used in image quality assessment during quality control tests in breast screening locations and other health centers. The mammographic phantom is comprised of a reference point, a glandular tissue step wedge, contrast and resolution targets, and groups of microcalcifications and fibers. The MCNP radiation transport code (version 4c2) has been modified and recompiled to let use of a large number of tallies and detectors per input file, and an azimuthal directional source biasing. The output surface air kerma (OSAK) delivered by the X-rays has been scored employing a rectangular matrix of point detectors (F5 tally) under the phantom, simulating the image system. Some variance reduction techniques have been implemented to ensure that photons reach the detectors and that weight fluctuations were reduced. The characteristic curve of the film-scanner imaging system combination has been obtained throughout several experimental measures with an aluminium sensitometric wedge and Monte Carlo simulations. The reconstructed images agree with the range of values, indicating that this method would be suitable for training purposes, phantom designing or dose calculations. PMID- 17271973 TI - Measurement of ocular torsion using iterative optical flow. AB - This work represents a new method for measuring ocular torsion using optical flow. Feature points are obtained from reference and current image, and the relative optical flows of each point are calculated. The feature points are selected according to the strength of corner on the signature of iris. This method is robust and effective in calculation. PMID- 17271974 TI - DSP based image processing for retinal prosthesis. AB - The real-time image processing in retinal prosthesis consists of the implementation of various image processing algorithms like edge detection, edge enhancement, decimation etc. The algorithmic computations in real-time may have high level of computational complexity and hence the use of digital signal processors (DSPs) for the implementation of such algorithms is proposed here. This application desires that the DSPs be highly computationally efficient while working on low power. DSPs have computational capabilities of hundreds of millions of instructions per second (MIPS) or millions of floating point operations per second (MFLOPS) along with certain processor configurations having low power. The various image processing algorithms, the DSP requirements and capabilities of different platforms would be discussed in this paper. PMID- 17271975 TI - Feature level fusion of multimodal medical images in lifting wavelet transform domain. AB - A method for feature level image fusion for multimodal medical images in second generation wavelet domain (lifting wavelet transform domain) is proposed. The feature fused is edge and boundary information of input images that is extracted using wavelet transform modulus maxima criterion. The image fusion performance is evaluated by standard deviation, entropy, cross entropy and gradient parameters. Experimental results show that the proposed method gives better results for image fusion as image contrast, average information content and detail information of fused image are increased. This method has further advantages of fast implementation, flexibility, saving of auxiliary memory, property of perfect reconstruction and simplicity as we have used lifting wavelet transform. The reduction in computational complexity has been achieved by a factor of two as compared to the nonlifted wavelet transform. PMID- 17271976 TI - Texture analysis of the endometrium during hysteroscopy: preliminary results. AB - The objective of this study is to investigate the usefulness of texture analysis in the endometrium during hysteroscopy in endoscopic imaging of the uterine cavity. Endoscopy images from the endometrium from three subjects, at optimum illumination and focus, were frozen and digitized at 720x576 pixels using 24 bits color. Regions of interest (ROI) of normal (N=61) and abnormal (N=69) regions were manually selected by the physician. ROI images were converted into gray scale and statistical features (SF) and spatial gray level dependence matrix features (SGLDM) were computed. The nonparametric Wilcoxon rank sum test at a=0.05 was carried out for comparing the differences between normal and abnormal tissue. There was significant difference between normal and abnormal endometrium for the SF features variance, energy and entropy and for the SGLDM feature of angular second moment. There was no significant difference for the SF features mean, median, and SGLDM features of contrast, correlation and homogeneity. PMID- 17271977 TI - Automatic determination of pedicle screw size, length, and trajectory from patient data. AB - Pedicle screw insertion is an orthopaedic spinal fixation procedure involving the placement of screws through individual spine pedicles and secured in spinal vertebrae. Pedicle anatomy varies widely within and across the patient population, and many complications have been reported with the surgical technique. To reduce complications, an automated procedure was developed that utilizes patient-specific medical imaging data to predetermine optimum pedicle screw size, length, and trajectory. The procedure involves importing medical imaging scans into the software, creating uniform voxel data for algorithm simplicity, segmenting the bony anatomy of the spine and defining its boundary, and identifying the pedicle using a search algorithm. The operations are performed in two-dimensions in the coordinate system of the medical imaging data. For each image slice, the minimum pedicle width is identified, and examining all slices identifies the overall minimum pedicle width. The optimum trajectory is determined using a 3D linear least squares fit to the array of minimum pedicle width midpoints. With the optimum trajectory determined, the maximum screw size and length are determined. PMID- 17271978 TI - Liver CT-image retrieval based on Gabor texture. AB - Gabor schemes of image representation have shown great success in many texture related computer vision applications. This is mainly because the primitives of image representation in vision have a wavelet form similar to Gabor elementary functions (GEF's). We use Gabor approach to analyze the texture of liver CT images and extract the corresponding feature vectors. Then, the feature vectors are used to facilitate content-based image retrieval (CBIR). In experiments, a batch of liver CT images containing several types of CT findings is collected, and retrieval results by Gabor texture are present. PMID- 17271979 TI - Image pre-processing methods for palm print authentication. AB - We propose a ridge detection method for palm print identification using low resolution images. Before the image processing such as Hough transform, we focused on extracting the exact principle line of palm print using contours. To solve the LF (local flatness) problem on the image, we used the DAROC (downhill along the ridges on the contours) algorithm utilizing distance, angle and momentum. PMID- 17271980 TI - Evaluation of variability and significance of fundus camera lens distortion. AB - Six digital fundus cameras were examined to determine degrees of distortion introduced by lenses. Results quantified lens distortion effects on fundus images and demonstrate intrinsic properties in similar camera systems may vary. PMID- 17271981 TI - Evaluation of the methods for pupil size estimation: on the perspective of autonomic activity. AB - The purpose of This work is to find the optimal calculation method about pupil size to estimate an activity of autonomic nerve system. To evaluate its state, we have to calculate an accurate pupil size from the image of free-rotated and yawed eye for 5 minutes. But calculation of the pupil size from image takes a long time. So we suppose three methods which considered cost (time), accuracy and evaluate for each. 'Method' 1 is to calculate the vertical pupil diameter from images, 'method 2' is to calculate the pupil size from whole image (method 2-1; by binarization and method 2-2; by binarization with shape evaluation) and 'method 3', the most accurate method, is from three-dimensional transformation of pupil image. As a result, for seven subjects, each method is takes about 6, 44, 124, 311 minutes to evaluate five-minute images (300,000 pixels/frame, 30 frames/sec). Also, the result of correlation between the parameter Lf/Hf ratio of heart rate variability, commonly used method for estimate the state of autonomic nerve system, and it of pupil size variability is, for each case, 0.34, 0.2, 0.69, 0.69. PMID- 17271982 TI - Fundus based eye tracker for optical coherence tomography. AB - Current optical coherence tomography (OCT) relies on patient cooperation to maintain fixation. For patients with eye complications, it is extremely difficult to achieve fixation on the eye. Most eye trackers are external and track only the pupils. Such method is not useful for the OCT. The only existing fundus image based tracker is a hardware-based system that is composed of a confocal reflectometer, dither scanner, and tracking galvanometers. The integration of such hardware based system with the OCT is not as desirable nor as portable. Therefore, we want an eye tracking system that can be installed in the computer connected to the OCT. In this paper, a real time internal eye tracking software based system is proposed. By combining intensity based object tracking adaptive mean shift algorithm with Kalman filtering techniques together, a robust real time eye tracking algorithm is proposed. The system is robust in terms of its acceptance to low resolution, coarsely quantized, or extremely noisy images and still able to produce desirable results with no pre-processing of images. PMID- 17271983 TI - Morphological image sharpening by double structuring elements for ultrasound images. AB - We discuss a new morphological operations using double structuring elements (DSEs) and apply them to image sharpening of ultrasound B-mode images with speckle pattern. The DSEs, a couple of two different structuring elements, varying with the local characteristics of the input image, yield an edge sharpening effect. General single structuring element does not have the sharpening function. Our method improves contrast at the tissue boundary without speckle emphasis and does not generate overshoot nor undershoot around the boundary. We demonstrate its effectiveness in experiments using human thyroid images. PMID- 17271984 TI - Hand region extraction and gesture recognition from video stream with complex background through entropy analysis. AB - Hand gesture recognition utilizing image processing relies upon recognition through markers or hand extraction by colors, and therefore is heavily restricted by the colors of clothes or skin. We propose a method to recognize band gestures extracted from images with a complex background for a more natural interface in HCI (human computer interaction). The proposed method obtains the image by subtracting one image from another sequential image, measures the entropy, separates hand region from images, tracks the hand region and recognizes hand gestures. Through entropy measurement, we have color information that has near distribution in complexion for regions that have big values and extracted hand region from input images. We could draw the hand region adaptively in variable lighting or individual differences because entropy offers color information as well as motion information at the same time. The detected contour using chain code for the hand region is extracted, and present centroidal profile method that is improved little more and recognized gesture of hand. In the experimental results for 6 kinds of hand gesture, it shows the recognition rate with more than 95% for person and 90-100% for each gesture at 5 frames/sec. PMID- 17271985 TI - Facial expression analysis for estimating patient's emotional states in RPMS. AB - Currently, a range of remote patient monitoring systems (RPMS) are being developed to care for patients at home rather than in the costly hospital environment. These systems allow remote monitoring by health professionals with minimum medical intervention to take place. However, they are still not as effective as one-on-one human interaction. The face and its features can convey patient cognitive and emotional states faster than electrical signals and facial expression can be considered as one of the most powerful features of RPMS. We present image pre-processing and enhancement techniques for face recognition applications. In particular, the project is aimed to improve the performance of RPMS, taking into account the cognitive and emotional state of patients by developing a more human like RPMS. The techniques use the value of grey scale of the images and extract efficient facial features. The extracted information is fed into input layer of an artificial neural network for face identification. On the other hand, the colour images are used by the recognition algorithm to eliminate nonskin coloured background and reduce further processing time. A data base of real images is used for testing the algorithms. PMID- 17271986 TI - An elliptic PDE approach for shape characterization. AB - This work presents a novel approach to analyze the shape of anatomical structures. Our methodology is rooted in classical physics and in particular Poisson's equation, a fundamental partial differential equation, The solution to this equation and more specifically its equipotential surfaces display properties that are useful for shape analysis. We present a numerical algorithm to calculate the length of streamlines formed by the gradient field of the solution to this equation for 2D and 3D objects. The length of the streamlines along the equipotential surfaces was used to build a new function which can characterize the shape of objects. We illustrate our method on 2D synthetic and natural shapes as well as 3D medical data. PMID- 17271987 TI - Automatic detection of camera translation in eye video recordings using multiple methods. AB - In video eye tracking, shifting of the camera relative to the head can introduce artifacts. This work proposes a new combination of image processing techniques to automatically detect and measure the relative translation of cameras separately imaging the left and right eyes. It uses a priori physiological knowledge to improve the accuracy of algorithms. The first method compares an eye image with a reference frame using cross-correlation methods. The second isolates the upper eyelid and compares it with a reference frame to improve approximation of camera translation. The third creates an eyelid template from multiple frames and cross correlates it with each image frame. The later has the highest accuracy, with a mean error of 1.3 pixels. It is more robust since it eliminates features of the image that may introduce errors. This excellent accuracy makes the method a viable solution for the problem of camera movement relative to the head. PMID- 17271989 TI - Filtering and contrast enhancement on subtracted direct digital angiograms. AB - This work presents the results of a research related to medical image subtraction algorithms. The selected area is of direct digital X-ray angiography, where subtraction algorithms are the basis of most acquisition and reviewing protocols. The goal of this research is to analyze the currently existing image subtraction algorithms and to propose a new approach based on the experienced limitations, respectively to develop a new imaging technique that allows both contrast agent and radiation dose reduction. The enhancement of the subtraction algorithms is targeted by two means: a) noise reduction on image frames, b) identification of contrast agent injected regions. Both aspects will be studied based on the analysis of the spatio-temporal signal variation that image pixel intensities represent, therefore the resulting algorithm can not be used real time during image acquisition, but as a post processing technique during review. The temporal variation of pixel intensities was then analyzed and a patter check was followed to identify pixels being part of a contrast agent injected region. This information was used to highlight regions of interest and to increase the contrast in poorly injected areas. PMID- 17271988 TI - Computer-aided diagnosis system for acute stroke using diffusion weighted images with volume calculation. AB - The diffusion weighted image (DWI) technique is routinely used for diagnosis and treatment of early stroke due to its superior performance, especially when it is compared with conventional magnetic resonance image (MRI) for detection of acute ischemic stroke. Using DWI examination, This work has proposed a computer-aided diagnosis system, which can effectively calculate the volume size of a lesion and provide clinical doctor the 3D reconstruction data of the lesion. The potential benefits of using our system include the higher accuracy of acute stroke lesion definition, the reduced time and procedure of calculating the volume of a lesion, and providing 3D reconstruction image of stroke patients, which can effectively assist doctors in making more accurate diagnoses and treating patients in a more convenient way. Compared with the traditional method, the experimental results have shown the superior performance of this proposed system. PMID- 17271990 TI - Quantitative and qualitative evaluation of filter characteristics for wavelet packet compression of MR images. AB - We present an analysis of the characteristics of different filters for the compression of magnetic resonance images. Compression rates were 33:1 and 50:1. We compare the performance among different types of wavelets presented in the literature and provide quantitative (percentage of energy retained, peak signal to noise ratio) and qualitative (analysis by a group of seven experts) data to support our conclusions. Different types of coiflets, symlets and biorthogonal wavelets are analyzed, and we conclude that for the images under study (T1 weighed images in three planes), the best results are provided by the biorthogonal spline (Daubechies) wavelet 2,6. Several explanations for these results are mentioned. PMID- 17271991 TI - Wavelet transform domain data embedding in a medical image. AB - In this work, we propose a wavelet-based technique for embedding medical data in a medical image. In the spectral domain, the patient data are embedded into the wavelet coefficients of the host image. A diagnostic distortion measure (DDM) has been defined to measure the visible distortions between the original image and the embedded image. The performance of the DDM has been compared with the standard PSNR characteristics. The results show that DDM not only captures the distortions for different quantities of embedded data but also can quantify the differences when the same data are embedded at different subbands. The embedment of data into the mid and high frequency subbands of the host image show lower values of DDM and higher values of PSNR. PMID- 17271992 TI - Lung strain profiles using computed tomography elastography. AB - Using noninvasive medical imaging techniques to observe internal organs can result in more accurate diagnoses, while avoiding uncomfortable, expensive invasive procedures such as biopsies. One such technique, elastography, uses pairs of ultrasonic images (relaxed and compressed) to create an image called a strain diagram or an elastogram. Elastography has been shown to be useful for detecting and characterizing lesions in nonporous tissue, but fails to provide results for porous tissue such as the lung due to the limitations of ultrasound. Fortunately, X-rays are not limited by tissue-air boundaries and thus X-ray computed tomography elastography (CTE) promises to enable diagnosis and monitoring of ailments such as emphysema or interstitial lung disease. This paper presents improvements upon existing elastography techniques and applies them to CT scans of porous material. Specifically, the improvements include (1) pre correlation edge detection filtering, and (2) the implementation of 2-D techniques. Edge detection, performed with a first derivative filter, is shown to result in a higher correlation between relaxed and compressed images. This is especially true for feature-rich lung images, which consist of many small pockets of air-filled tissue. This paper also shows the benefit of employing 2-D techniques, even to a 1-D problem. PMID- 17271993 TI - A tool for the quantitative spatial analysis of mammary gland epithelium. AB - In this paper we present a method for the spatial analysis of complex cellular systems based on a multiscale study of neighborhood relationships. A function to measure those relationships, M, is introduced. The refined relative neighborhood graph is then presented as a method to establish vicinity relationships within layered cellular structures, and particularized to epithelial cell nuclei in the mammary gland. Finally, the method is illustrated with two examples that show interactions within one population of epithelial cells and between two different populations. PMID- 17271994 TI - The application of Efron's bootstrap methods in validating feature classification using artificial neural networks for the analysis of mammographic masses. AB - Efron's bootstrap resampling method is used to analyze the performance of artificial neural networks (ANNs) in the area of feature classification for the analysis of mammographic masses. The purpose of feature classification in mammography is to discover the salient information that can be used to discriminate benign from malignant masses. The performance of ANNs is typically measured in terms of the area under the receiver operating characteristics (ROC) curve (A/sub z/). Performance uncertainty problems and the generalization problems of ANNs are still the critical issues that impede the further application of ANNs in clinical medicine. It is unreasonable and impractical to justify the performance of one ANN being better than another just by its best A/sub z/ value. Efron's bootstrap methods make it possible to quantitatively analyze the performance of ANNs and anticipate its change tendency with relatively high accuracy. Our experimental results show that the probability model of A/sub z/ is close to a normal distribution. The performance of ANNs is more sensitive to the change of topology than that of the size and the composition of the training set. Bootstrap methods can be used to find the optimal epochs and avoid overfitting. PMID- 17271995 TI - Analysis on the influence of tissues/organs' movements in EIT images of lung ventilation using finite difference thorax models. AB - Monitoring lung air and fluid volume is a promising EIT application. Respiratory activity causes both chest expansion and position changes of tissues/organs in the thorax, which contributes measurement error. In EIT application, the electrodes are placed around chest in a two-dimensional ring, and image is reconstructed on the assumption that the object is two-dimensional and the images are due to resistivity change. EIT reconstruction algorithms generally do not consider organ and tissue positional change. Finite difference models (FDM) were developed based on MR images with different air volumes and used to study the effect of tissues/organs' motion. Results show that the tissues/organs' motion influence the region around the heart, which introduce the artifacts in the middle anterior region. The tissues/organs' motion also increases the resistivity change in the lung regions, which cannot be neglected. We conclude that tissues/organs' motion can cause serious error in the interpretation of EFT ventilation images. PMID- 17271996 TI - Comparison of scene-based interpolation methods applied to CT abdominal images. AB - Three-dimensional (3-D) interpolation from 2-D image slices is widely used to aid the display, analysis and other biomedical image processing. We investigate the performance of 5 scene-based interpolation methods: linear, cubic spline, modified cubic spline and sine-based functions (Dirichlet apodization and Hanning apodization). We test our methods on four sets of computed tomography (CT) abdominal images, which have more organs in them compared to other biomedical images. Results show that, contrary to the 1-D or 2-D cases, linear interpolation acts as well as, even slightly better than all the other methods in the sense of signal to noise ratio in most cases, while the computational load of linear interpolation is only about half of the other methods. The reason for the relative high performance of linear interpolation is probably the large distance between consecutive images, which indicates low inter-slice correlation. PMID- 17271997 TI - A new automatic skeletonization algorithm for 3D vascular volumes. AB - Extraction of the skeleton of vascular structures is an important procedure for computer aided analysis of vascular data. A new automatic skeletonization algorithm for 3D vascular volumes is proposed. Two types of distance maps and clusters, a set of connected points with the same property are used to represent the vascular structure. Using clusters representation, branch information can be retrieved efficiently. In each identified branch, preliminary points, defined as skeleton nodes, are derived hierarchically which are later interpolated to generate the skeleton. The algorithm was tested on MR angiography arterial and venous 3D vascular volumes. The extracted skeletons were reliable representation of the vascular structure. Compared to other 3D distance-based skeletonization algorithms, the new approach yields a more centered skeleton without complex post processing. The skeleton is also insensitive to boundary complexity and can be easily modified by the user. PMID- 17271998 TI - Robust phase sensitive inversion recovery imaging using a Markov random field model. AB - This paper presents a novel method for phase sensitive inversion recovery (PSIR) imaging for improved T/sub 1/ contrast. This method models the phase of the complex magnetic resonance image using a statistical model based on Markov random fields. A computationally efficient optimization method is developed. Computer simulations and in-vivo brain imaging experiments show that the proposed method can produce PSIR images with enhanced T/sub 1/ contrast and it is robust against high levels of data noise even when rapid phase variations are presented. PMID- 17271999 TI - 3D average human corneal models. AB - In this paper we propose a method of building an average model or atlas of the cornea based on topographic data. Specific models can be constructed for the left or right eye, gender, age, or ametropia, to assess differences and similarities. An application of this atlas construction methodology to the study of corneal shape evolution with age is presented. Results show significant differences between age groups. This numerical atlas could also be helpful in the design of algorithms targeting the detection of corneal shape abnormalities, such as keratoconus or previous laser surgery. PMID- 17272000 TI - Microcalcifications detection in digital mammograms. AB - A method is presented for detecting minimally sized microcalcifications on ma mammograms to add extra security to the radiologist's classification. The method imitates the normal procedure followed by the specialist, and is easily implemented on low-cost PCs. As input, it accepts the usual digital mammograms. Tested against one of the most extensive databases - the DDSM of the University of South Florida - it gave a 100% success rate. For any suspicious regions (the so-called regions-of-interest or ROI) a separate image of suitable size is generated and displayed. The system also allows feature vectors to be generated for use in an automatic classifying system - such as a neural network (NN) - to determine the malignancy of the ROIs that were detected. PMID- 17272001 TI - Normal mammogram classification based on a support vector machine utilizing crossed distribution features. AB - Automatic classification of normal mammograms, which constitute a majority of screening mammograms, is a new approach to computer-aided diagnosis of breast cancer. This approach may be limited, however, by non-separable "crossed" distributions of features that are extracted from digitized mammograms. This work presents a method of mapping such non-separable input features into a new set of separable features that can be utilized, together with ordinary "uncrossed" features, by a support vector machine (SVM) classifier. The results of the proposed scheme show improved performance with 80% sensitivity and 95% specificity. PMID- 17272002 TI - Applying modular classifiers to mammographic mass classification. AB - Classification is the last step in the computer aided diagnosis (CAD) system for determining whether a breast mass segmented from a digital mammogram is malignant or benign. Hence it is important to improve sensitivity at this stage. This work investigates the use of modular classifier (MoC) schemes, namely bagging and adaboost algorithms, for automated classification of mammographic masses. CAD systems containing a MoC are compared to CAD systems that contain traditional classifiers (TrC), for example single nearest mean or maximum likelihood classifiers. This study included 200 digitized mammograms, each manually segmented by a radiologist. In order to test the MoC and TrC approaches, conventional shape based features were extracted from the segmented masses. These features were then optimized using Fischer's linear discriminant analysis (LDA). When no LDA was utilized, it was observed that MoC schemes increased the sensitivity from 74% to 83% over the TrC approaches. After performing LDA, the sensitivity increased from 83% to 88% for TrC and MoC schemes, respectively. PMID- 17272003 TI - A novel computerized approach to enhancing lung tumor detection in whole-body PET images. AB - Positron emission tomography (PET) is complimentary to other imaging modalities such as CT and MRI and provides a unique and effective means for detecting tumors in vivo through tissue metabolism measurement. At the majority of clinics, only the attenuation-corrected images are read by the physician for tumor diagnosis; the unconnected images are not examined, losing critically important information for a small portion of patients. We have developed a novel image processing method capable of automatically detecting and ranking tumor candidates in the lungs using the whole-body PET images. The intended utility is to visually prompt tumor candidates, assisting the physician to achieve better diagnosis, especially when the candidates appear to be subtle. The technique takes advantage of different information contents in the emission, corrected and uncorrected images. It processes the images three-dimensionally and the processing consists of segmentation, multi-thresholding with volume criterion, and heuristics-based tumor candidate ranking. This method is fast in computation and display and thus is suitable for real-time applications using high-end PCs. Our preliminary retrospective study involving nine patients has yielded promising results. PMID- 17272004 TI - Early diagnosis of skin cancer based on segmentation and measurement of vascularization and pigmentation in Nevoscope images. AB - This work presents techniques developed for automated image segmentation and classification of skin lesions as malignant or benign based on the ground truth. For each skin lesion two images are obtained, one in each of two different modalities of epiluminescence microscopy (ELM): side-transillumination which highlights the subsurface vasculature and surface pigmentation, and cross polarization, which only highlights the details of skin surface pigmentation. The automated procedure consists of three steps: i) Segmentation of images, using three segmentation methods; ii) Selection of the most accurate segmentation results based on a weighted scoring technique; and iii) classification of the lesion as malignant or benign by verifying the presence of a ring of hypervascularity around the lesion in the side transillumination images. The segmentation results were validated against manual segmentation by an expert and the malignancy results were validated against the result from pathology. PMID- 17272005 TI - A study on the image diagnosis of melanoma. AB - At present the diagnosis of melanoma is mainly performed based on the experience of each doctor. The doctors need some objective measure for diagnosis of melanoma and nevus. But there are few researches on objective index for the diagnosis. This workr deals with features of melanoma and nevus for computer diagnosis. First, we extracted the contour of lesions with image processing. One hundred five values of features were computed based on ABCD-rule. Discriminant analysis showed the accuracy of 96.0% (specificity of 98.3 % and the sensitivity of 90.0%). The results obviously showed the difference between melanoma and nevus. PMID- 17272006 TI - Fingerprint image enhancement based on nonlinear anisotropic reverse-diffusion equations. AB - We present an approach based on nonlinear anisotropic reverse diffusion equations (NARDE) to enhance noisy fingerprint images. After studying the nonlinear diffusion equations to denoised images and nonlinear reverse diffusion process in nature, a new scheme is advanced with new selection criteria of optimal stopping time. Experiments were carried out and showed the high efficiency of the noise removing sharpening scheme and the role of selection criteria on noisy fingerprint images. PMID- 17272007 TI - Spatially adaptive wavelet thresholding of rubidium-82 cardiac PET images. AB - 82Rb positron emission tomography (PET) images can be used to diagnose coronary artery disease (CAD), but deterioration of the images due to noise can compromise their quality. This work presents our work on a wavelet-based thresholding method for denoising cardiac /sup 82/Rb PET images. Our approach is based on a three dimensional (3D) discrete dyadic wavelet transform, with iterative thresholding of coefficients being performed in a spatially adaptive context. A subjective analysis indicates that this technique leads to better discrimination between diagnostically significant features and noise when observing the denoised images and the corresponding cardiac polar maps. Results are presented for cardiac PET images of a normal subject (low risk of CAD) using a figure of merit based on expected image properties for such a patient. The increase in image quality is substantial when the proposed method is compared to conventional denoising protocols. PMID- 17272008 TI - Ultrasonic speckle suppression using robust nonlinear wavelet diffusion for LV volume quantification. AB - This work proposes a novel speckle suppression method, called robust nonlinear wavelet diffusion. It shows that the log-transformed speckle can be approximated by Gaussian noise contaminated with long burst outliers. Consequently, we exploit this knowledge to design a speckle suppression filter within the framework of wavelet analysis. The outliers are removed by the combination of the robust residual filter and nonlinear diffusion filter, and the Gaussian noise is eliminated by the wavelet soft-shrinkage technique. We validate the proposed method using synthetic and real echocardiographic images. The performance improvement over other traditional denoising filters is quantified in terms of noise suppression and structural preservation indices. Finally, using the denoised image, we improve the performance of the gradient vector flow snake by modifying its external force field, and we quantify the volume of left ventricle via segmentation applied to the echocardiographic image. PMID- 17272009 TI - Contrast enhanced ultrasound image segmentation based on fuzzy competitive clustering and anisotropic diffusion. AB - Doppler has been used for many years for cardiovascular exploration in order to visualize the walls and anatomical or functional diseases. The use of ultrasound contrast agents makes it possible to improve ultrasonic information. Thus, harmonic imaging is a powerful tool for characterizing pathologies by their vascularity. However, images are buried in noise. We present an approach for noise reduction and structural features enhancement based on nonlinear anisotropic diffusion, coupled with fuzzy clustering segmentation to delineate liver pathologies. PMID- 17272010 TI - Regularization of PET reconstruction using multi-scale adaptive thresholding. AB - A multi-scale adaptive thresholding scheme is presented in this study. It was evaluated as a regularization process to filtered back-projection (FBP) for reconstructing clinical PET brain data. Adaptive selection of thresholding operators for each multi-scale sub-band enabled a unified process for noise removal and feature enhancement. A cross-scale regularization process was utilized as an effective signal recovering operator. Together with non-linear thresholding and enhancement operators, they offered remarkable postprocessing to FBP reconstructed data. In addition, such effectiveness was formulated as a regularization process to optimize FBP reconstruction. A comparison study with multiscale regularized FBP (MFBP), standard FBP with clinical settings and iterative reconstruction (OSEM) was reported. The proposed regularization process has shown competitive improvement in the image quality of PET reconstructions when compared to the current state-of-the-art method used in clinical commercial systems (OSEM). PMID- 17272011 TI - A new tracking system for the robust extraction of retinal vessel structure. AB - Identification and measurement of blood vessels in retinal images could allow quantitative evaluation of clinical features, which may allow early diagnosis and effective monitoring of therapies in retinopathy. A new system is proposed for the automatic extraction of the vascular structure in retinal images, based on a sparse tracking technique. After processing pixels on a grid of rows and columns to determine a set of starting points (seeds), the tracking procedure starts. It moves along the vessel by analyzing subsequent vessel cross sections (lines perpendicular to the vessel direction), and extracting the vessel center, calibre and direction. Vessel points in a cross section are found by means of a fuzzy c means classifier. When tracking stops because of a critical area, e.g. low contrast, bifurcation or crossing, a "bubble technique" module is run. It grows and analyzes circular scan lines around the critical points, allowing the exploration of the vessel structure beyond the critical areas. After tracking the vessels, identified segments are connected by a greedy connection algorithm. Finally bifurcations and crossings are identified analyzing vessel end points with respect to the vessel structure. Numerical evaluation of the performances of the system compared to human expert are reported. PMID- 17272013 TI - Classification of protein crystallization imagery. AB - We investigate automatic classification of protein crystallization imagery, and evaluate the performance of several modern mathematical tools when applied to the problem. For feature extraction, we try a combination of geometric and texture features; for classification algorithms, the support vector machine (SVM) is compared with an automatic decision-tree classifier. Experimental results from 520 images are presented for the binary classification problem: separating successful trials from failed attempts. The best false positive and false negative rates are at 14.6% and 9.6% respectively, achieved by feeding both sets of features to the decision-tree classifier with boosting. PMID- 17272012 TI - Retinal image analysis to detect and quantify lesions associated with diabetic retinopathy. AB - An automatic method to detect hard exudates, a lesion associated with diabetic retinopathy, is proposed. The algorithm found on their color, using a statistical classification, and their sharp edges, applying an edge detector, to localize them. A sensitivity of 79.62% with a mean number of 3 false positives per image is obtained in a database of 20 retinal image with variable color, brightness and quality. In that way, we evaluate the robustness of the method in order to make adequate to a clinical environment. Further efforts will be done to improve its performance. PMID- 17272014 TI - Robust classification of subcellular location patterns in high resolution 3D fluorescence microscope images. AB - Knowledge of a protein's subcellular location is essential to a complete understanding of its functions. Automated interpretation methods for protein location patterns are needed for proteomics projects, and we have previously described systems for classifying the major subcellular patterns in cultured mammalian cells. We describe here the calculation of improved 3D Haralick texture features, which yielded a near-perfect classification accuracy when combined with 3D morphological and edge features. In particular, a set of 7 features achieved 98% overall accuracy for classifying 10 major subcellular location patterns in HeLa cells. PMID- 17272015 TI - Joint segmentation and classification of M-FISH chromosome images. AB - Automatic segmentation and classification of M-FISH chromosome images are jointly performed using a six-feature, 25-class maximum-likelihood classifier. Preprocessing of the images including background correction and six-channel color compensation method are introduced. A feature transformation method, spherical coordinate transformation, is introduced. High correct classification results are obtained. PMID- 17272016 TI - Techniques for automatic spinal cord histology characterization for validation of diffusion tensor imaging. AB - One current focus in diffusion tensor imaging is the validation of DT-MR measurements against histological slices. Current methods require manual correlation by visual inspection. We present algorithms which automatically analyze spinal cord histology slices based on Fourier and morphological operators. They accurately discriminate regions dominated by in-plane caudal cranial fibers from in-plane axial fiber dominated regions, and can then be used to validate angular direction, anisotropy, and relative eigenvalue estimates from DT-MR. PMID- 17272017 TI - Radial basis functions-simulated annealing classification of mammographic calcifications. AB - We investigated several approaches to classify mammographic calcifications as malignant or benign: a supervised classifier, multi-layer perceptron (MLP), a supervised and unsupervised classifier, a classifier based upon adaptive resonance theory with linear discriminant analysis (ART2LDA), and a classifier based upon nonlinear and combinational optimization techniques: RBF (radial basis functions)-simulated annealing. The classifiers were trained using shape factors extracted from 143 mammographic calcifications (79 malignant and 64 benign), adopting the leave-one-cut procedure. The classifiers' performance was compared in terms of the area under the ROC curve. The best result of 0.97 was obtained with RBF-simulated annealing, which was significantly better than the results obtained with MLP and ART2LDA, which were, respectively, 0.70 and 0.71. PMID- 17272018 TI - Segmentation of articular cartilage using active contours and prior knowledge. AB - A diffusion snake segmentation algorithm was evaluated on synthetic and real MR images of articular cartilage. The algorithm proved to be robust to missing boundaries and the initial contour converges over large distances. Compared with a standard B-spline snake, more accurate and reproducible segmentations were obtained, with less effort during initialization of the algorithm. PMID- 17272020 TI - Model-based automated segmentation of kinetochore microtubule from electron tomography. AB - The segmentation of kinetochore microtubules from electron tomography is challenging due to the poor quality of the acquired data and the cluttered cellular surroundings. We propose to automate the microtubule segmentation by extending the active shape model (ASM) in two aspects. First, we develop a higher order boundary model obtained by 3-D local surface estimation that characterizes the microtubule boundary better than the gray level appearance model in the 2-D microtubule cross section. We then incorporate this model into the weight matrix of the fitting error measurement to increase the influence of salient features. Second, we integrate the ASM with Kalman filtering to utilize the shape information along the longitudinal direction of the microtubules. The ASM modified in this way is robust against missing data and outliers frequently present in the kinetochore tomography volume. Experimental results demonstrate that our automated method outperforms manual process but using only a fraction of the time of the latter. PMID- 17272019 TI - A region-based approach combining marker-controlled active contour model and morphological operator for image segmentation. AB - This paper presents a segmentation method for medical images. The goal is to localize and parameterize the blood vessel in these images for subsequent analysis. We proposed a new segmentation strategy that combines a marker controlled active contour model and the mathematical morphology methodology. The algorithm presented in this paper is based on mathematical morphology operator and the implicit active contour or level sets for the detection of vessel-like pattern. The initial guess for the contour is from the vessel-like pattern contour marked and controlled by the user. The contour is then moved by image driven forces to the boundaries of the blood vessel using morphological operators: erosion, dilation, opening, and closing. We focus on the robustness of the sensitivity of the morphological operator and also the initialization and the placement of the initial contour. The experiment results are evaluated visually and quantitatively for its robustness in detecting blood vessels in medical images. PMID- 17272021 TI - Adaptive FCM with contextual constrains for segmentation of multi-spectral MRI. AB - An adaptive fuzzy c-means (FCM) clustering algorithm is explored for segmentation of three-dimensional (3D) multi-spectral MR images. This algorithm takes into consideration of both noise and 3D intensity non-uniformity. This algorithm models the intensity nonuniformity of MR images as a gain field or bias field that slowly varies in space, which is approximated by a linear combination of smooth basis functions made up of polynomials with different orders. The contextual constraints are included by introducing a regularization term into the cost function of FCM. The regularization term is a measure of aggregation of local voxels that tend to overcome the noise in voxel labeling. We present our scheme both for bias and gain fields, with special attention is paid to robust estimation of the bias field. PMID- 17272022 TI - Knowledge-based 3D segmentation and reconstruction of coronary arteries using CT images. AB - An approach for the 3D segmentation and reconstruction of human left coronary arteries using angio-CT images is presented in This work. Each voxel in the 3D dataset is assumed to belong to one of the three homogeneous regions: blood, myocardium, and lung. A priori knowledge of the regions is introduced via Bayes' rule. Posterior probabilities obtained using Bayes' rule are anisotropically smoothed, and the 3D segmentation is obtained via MAP classifications of the smoothed posteriors. An active contour model is then applied to extract the coronary arteries from the rest of the volumetric data with subvoxel accuracy. The geometric model of the left coronary arteries obtained in this work may be used to provide accurate boundary conditions for hemodynamic simulations, or to provide objective measurements of clinically relevant parameters such as lumen sizes in a 3D sense. PMID- 17272023 TI - Quantification of breast tissue index from MR data using fuzzy clustering. AB - The study objective was to develop a segmentation technique to quantify breast tissue and total breast volume from magnetic resonance imaging (MRI) data to obtain a breast tissue index (BTI) related to breast density. Our goal is to quantify MR breast density to improve breast cancer risk assessment for certain high-risk populations for whom mammography is of limited usefulness due to high breast density. A semi-automatic 3D segmentation technique was implemented based on a fuzzy c-means technique (FCM) to segment fibroglandular tissue from fat in the breast images. After validation on a phantom, our FCM technique was first used to test the breast tissue measures reproducibility in two consecutive MR examinations of the same patients. The technique was then applied to measure the BTI on 10 high-risk patients. Results of BTI obtained with the semi-automated FCM method were compared with BTI results for the same patients using two other techniques, manual delineation and global threshold. BTI measures correlated well with mammographic densities (Pearson coefficients r = 0.78 using MR manual delineation, and r = 0.75 using MR FCM). The breast tissue index could therefore become a common measure for future studies of using noncontrast MRI data. PMID- 17272024 TI - Comparison study of clinical 3D MRI brain segmentation evaluation. AB - Although numerous methods to segment brain MRI for extraction of white matter, gray matter and cerebrospinal fluid (CSF) have been proposed for the past two decades, little work has been done to evaluate and compare the performance of different segmentation methods on real clinical data sets, especially for CSF. This study focuses on the comparison of the four following methods for segmentation of cerebral brain MRI: gray levels thresholding, three-dimensional level set, fuzzy connectedness and FSL. Quantitative evaluation of segmentation accuracy was performed with comparison to manual segmentation on a database of 10 adult subjects. PMID- 17272025 TI - Multimodal image re-registration via mutual information to account for initial tissue motion during image-guided neurosurgery. AB - Multimodal imaging modalities, such as high-resolution pre-operative MR (pMR) and intra-operative US (iUS), have been used widely to provide complementary information for guiding neurosurgery. Proper registration between the images is usually established fiducials placed on the patient skull, which can be identified both in MR and a tracking system that also records location and orientation of each iUS scan. Although such systems can achieve high registration accuracy, we have observed brain tissue motion with respect to the skull after the craniotomy and before opening of the dura. We developed a rigid registration strategy to re-align the brain in iUS and pMR to account for such motion. The mutual information between the two modalities is maximized through a genetic algorithm. Two patient cases are presented to show the improved registration accuracy of soft tissues. PMID- 17272026 TI - Multimodal matching by maximization of mutual information and optical flow technique. AB - Conformal radiotherapy is a therapeutic method requiring medical imaging, generally CT images to obtain Hounsfield number and electronic density data indications. The use of MRI simultaneously with CT imposes to deform CT images and superimpose them on MR images. The aim of this paper is to propose a nonrigid matching method between the two modalities (CT and MRI). The transformation model is defined by an optical flow registration algorithm, using mutual information as a similarity criterion. PMID- 17272027 TI - Gradient based nonuniform subsampling for information-theoretic alignment methods. AB - We examine the computation of information-theoretic image registration metrics and propose two (deterministic and stochastic) nonuniform subsampling methods for improving the efficiency. The proposed schemes attempt to use only the most relevant information as the basis of the computation. Both methods are shown to yield considerable improvement over the current practice of uniform subsampling. Theoretical and experimental evidence is provided. PMID- 17272028 TI - Physically correct mesh manipulation in multi-level free-form deformation-based nonrigid registration. AB - We present a new solution to prevent mesh folding artifacts common in free-form deformation-based nonrigid registration. Our algorithm imposes linear bounds on the search space of control point locations, thereby enabling the use of constrained optimization algorithms. We also introduce a new method for controlling the mesh rigidity, based on maximum voxel displacement. Our method allows local control of the deformation, based on a priori knowledge of the magnitude of possible local deformations. PMID- 17272029 TI - Automatic registration of serial mammary gland sections. AB - We present two methods for automatic registration of microscope images of consecutive tissue sections. They represent two possibilities for the first step in the 3-D reconstruction of histological structures from serially sectioned tissue blocks. The goal is to accurately align the sections in order to place every relevant shape contained in each image in front of its corresponding shape in the following section before detecting the structures of interest and rendering them in 3D. This is accomplished by finding the best rigid body transformation (translation and rotation) of the image being registered by maximizing a matching function based on the image content correlation. The first method makes use of the entire image information, whereas the second one uses only the information located at specific sites, as determined by the segmentation of the most relevant tissue structures. To reduce computing time, we use a multiresolution pyramidal approach that reaches the best registration transformation in increasing resolution steps. In each step, a subsampled version of the images is used. Both methods rely on a binary image which is a thresholded version of the Sobel gradients of the image (first method) or a set of boundaries manually or automatically obtained that define important histological structures of the sections. Then distance-transform of the binary image is computed. A proximity function is then calculated between the distance image of the image being registered and that of the reference image. The transformation providing a maximum of the proximity function is then used as the starting point of the following step. This is iterated until the registration error lies below a minimum value. PMID- 17272030 TI - Registration of bimodal retinal images - improving modifications. AB - The proper optical disc segmentation in images provided by confocal laser scanning ophthalmoscope and by color fundus-camera is a necessary step in early glaucoma or arteriosclerosis detection. Fusing information from both modalities into a vector-valued image is expected to improve the segmentation reliability. The paper describes a registration of these images using optimization based on mutual information criterion function extended with gradient-image mutual information. The controlled random search (CRS) has been found to be a more robust optimization routine than the simulated annealing (SA) while tested on a set of 174 image pairs. Finally, the multi-resolution algorithm for bimodal retinal image registration achieving the success-rate of 94% is proposed. PMID- 17272031 TI - Intra subject 3D/3D kidney registration/modeling using spherical harmonics applied on partial information. AB - One of the goal of the Nephron-Sparing Surgery preoperative planning is to delineate as exactly as possible the renal carcinoma and to specify its relations to the renal arterial, venous and collecting system anatomy. The classical preoperative imaging system is the spiral CT urography, which gives successive 3D acquisitions of complementary information about the kidney anatomy. The fusion of this information can be achieved by intra-patient registration techniques. However, because the kidney is difficult to demarcate from the liver or the spleen, a partial information registration technique should be used. In our paper we propose a methodology based on spherical harmonics, which can be used for partial information registration and also for the 3D kidney form modeling. PMID- 17272032 TI - Quantification of in vitro cell invasion through image analysis. AB - An image analysis method for quantification of in vitro cell invasion is presented. The method is designed for in vitro assays that are based on invasion of cells through a porous membrane. The images are obtained with a light microscope. The method has two major steps. The first one is the detection of the well in which invasion occurs. The second task is the detection of cells that have invaded through the membrane. The image processing techniques that are employed include thresholding and morphological filtering. Image processing results of in vitro invasion experiments and an analysis of robustness are presented to demonstrate the accuracy of the method. PMID- 17272033 TI - Efficient geometric algorithms for determining motion and shape deformation of coronary vessels. AB - Each year approximately 225,000 Americans die of vascular disease alone. For effective diagnosis and treatment of such diseases, accurate imaging of the complicated vascular structures is essential. Quantitative measures relating to motion and structural changes of vessels are extremely important for clinical diagnosis of such diseases. Current medical imaging techniques, however, cannot yet provide the necessary spatial/temporal resolution for such advanced analysis of the rapidly moving coronary vessels. Thus, a great deal of information between two consecutive image frames could be inherently lost. Furthermore, due to the low contrast in many images of coronary sequences, segmentation algorithms often fail to detect the exact vessel structures. We propose geometric techniques to recover the motion and deformation of coronary vessels between two image frames. Our techniques can be used to increase the temporal resolution of a coronary sequence to a desired level by predicting the motion and shape-deformation of the vessel-structure. They can also be used to predict the structure of the vessel in a low contrast image to complement the results of a vessel-detection/segmentation algorithm; when used in conjunction with such a segmentation technique, it will help alleviate false positives and false negatives. PMID- 17272034 TI - Measurement of ocular torsion using digital fundus image. AB - Computer-based objective measurement of the ocular cyclotorsion using digital fundus photograph was developed. Color digital fundus photographs acquired with the field angle of 60 degrees , 1520 x 1080 in resolution were analyzed. Optic disc and macula were segmented by the program developed on MATLAB, which executed the serial analysis of the Otsu threshold, labeling, Canny edge. The angle between the horizontal line that bisects the optic disc and the line connecting the center of optic disc and macula was measured and compared with the torsion determined by the specialist. Optic disc and macula were segmented and the mean of the calculated angle was 3.02+/-1.24 degrees . The mean of the torsion determined by the specialist was 3.13+/-1.98 degrees and there was no difference between the two. The measurement of the cyclotorsion using computer program showed good coincidence with that of the specialist and it can be a good candidate as a tool helping precise diagnosis and the objective evaluation of the disease for the physicians. PMID- 17272035 TI - Coronary extraction and stenosis quantification in X-ray angiographic imaging. AB - This work describes a method to quantify stenosis in X-ray coronary angiography. Vascular edge extraction is first performed based on a deformable spline algorithm. It makes use of directional S-Gabor filters to build an external energy field that is then used in a snake optimisation scheme. A string matching technique is then applied to match the contour points and obtain a trace between the matched points. This trace allows then computing the vessel diameter and deriving quantitative stenosis measurements. Experimental results are presented on simulated data and real images. PMID- 17272036 TI - Discrete optical flow estimation methods and their application in the extraction of motion strength signals from video recordings of neonatal seizures. AB - This work presents a methodology for the development of regularized optical flow computation methods for video. The proposed methodology is based on a discrete formulation of the optical flow problem. The optical flow computation methods produced by the proposed methodology are utilized to extract temporal motion strength signals from video recordings of neonatal seizures. PMID- 17272037 TI - Image registration for prostate MR spectroscopy using modeling and optimization of force and stiffness parameters. AB - We develop an image registration system based on biomechanical modeling of the prostate and surrounding tissues to register cancerous tumor locations for targeted prostate brachytherapy treatment planning. Cancerous tumors can be identified using magnetic resonance spectroscopy (MRS) imaging, which is acquired with an endorectal probe that causes significant nonlinear deformation of the prostate. The probe is removed during magnetic resonance (MR) imaging for brachytherapy planning and therapy. Given 2-dimensional segmented MR and MRS images, our finite element based model defines a mapping between the probe-in/out images by estimating the deformation of the prostate and surrounding tissues due to endorectal probe insertion and balloon inflation. Treating uncertain patient specific model parameters for tissue stiffness and external forces as variables, we compute a locally optimal solution to maximize image registration quality. We visualize results by applying the computed mapping to the MR image to generate a deformed MR image. We compare deformed MR images to corresponding MRS images for 5 patients and obtain an average dice similarity coefficient (DSC) of 95.6% for the prostate. Using the mapping, we warp a regular spectroscopy grid from the MRS image to the probe-out MR image for use during treatment planning. PMID- 17272038 TI - Planar visual fusion scintigraphy. AB - Planar scintigraphy, while providing useful information about the distribution of a particular radiopharmaceutical being imaged, often does not provide adequate information about the surrounding anatomical structures, thereby complicating diagnosis. We have therefore explored a means of fusing planar scintigraphic images with visual photographic images to supply an anatomic correlate to regions of radiopharmaceutical accumulation. The digital visual image will provide a context for the relevant structures in the scintigraphic image. Phantom data confirm registration accuracy to within 1 pixel. Inaccuracy of camera-patient distance results in <1% image size change per cm height error. Initial clinical imaging has subjectively been very useful in low background applications such as lymphoscintigraphy, whole body I-131 NaI imaging for thyroid cancer and In-111 white blood cell infection imaging. PMID- 17272039 TI - Brain image segmentation for virtual endoscopy. AB - This paper presents an algorithm for fuzzy segmentation of MR brain images. Starting from the standard FCM and its bias-corrected version BCFCM algorithm, by splitting up the two major steps of the latter, and by introducing a new factor gamma, the amount of required calculations is considerably reduced. The algorithm provides good-quality segmented 2-D brain slices a very quick way, which makes it an excellent tool to support a virtual brain endoscope. PMID- 17272041 TI - Automated image segmentation for breast analysis using infrared images. AB - In order to realize a fully automated thermogram analysis package for breast cancer detection, it is necessary to identify the region of interest in the thermal image prior to analysis. A nearly fully automated approach is outlined that is able to successfully locate the breast regions in most of the images analyzed. The approach consists of a sequence of Canny edge detectors to determine the body boundaries and to isolate the most likely candidates for the bottom breast boundary. Three different strategies for identifying the bottom breast boundary are investigated: a variation of the Hough transform to identify the curved edges in the image, an algorithm used to detect the longest connected edges that are not part of the body boundary, and a third approach involving the density of detected edges in the breast region. The last two methods show great promise in successfully segmenting the breasts. PMID- 17272040 TI - Segmentation of muscles for 3D representation of acupoints. AB - Based on the dataset of the male Visible Human and the VOXEL-MAN software, original work for 3D representation of acupoints and acupuncture treatment has been reported. To get a realistic model, segmentation is one of the most important procedures in the whole process. The interactive segmentation of objects on the basis of ellipsoidal regions in RGB-space greatly enhances the realism of 3D reconstructions of the Visible Human datasets. Furthermore, this article describes a double-ellipsoids method in RGB-space for the specific segmentation of muscles originally from our mass of work. The whole process can be interactively controlled by an operator via the tools developed by VOXEL-MAN. Some ideal results have been achieved in a short time. PMID- 17272042 TI - A method to register intra-treatment ultrasound images to pre-treatment images of prostate. AB - This paper describes a method to register ultrasound images (US) to pre-treatment images. The aim of the work is the information transfer between the pre-treatment imaging modality (MR or CT) and the intra-treatment imaging (US). Ultrasound images are spatially tracked by a stereo-vision system and the prostate boundaries are automatically extracted using a method that combines morphological and adaptive speckle suppression and a priori knowledge. MR/CT images are merged to construct a volume of pelvis using fuzzy logic algorithm and an MPR virtual slice corresponding to the orientation of the US image is generated from the volume. The prostate is segmented from the slice by a model-based method and rigidly registered by ICP algorithm to the US contour. Preliminary experiences gave satisfactory results with short computing time. PMID- 17272043 TI - Validation of an elastic matching algorithm based on complex wavelets for the realignment of dynamic MR breast images. AB - In this paper, a novel approach for the registration of dynamic magnetic resonance (MR) breast images is validated. The approach is fully automatic and it performs a multi-resolution motion field estimation based on complex discrete wavelets transform (CDWT). The validation was designed to assess the registration quality in patient breast data. A set of diagnostic features of MR breast image was defined and two expert radiologists were asked to score the capability to detect these features in the subtraction images. Two registration methods were compared: a rigid registration algorithm and the proposed approach. Results show that the novel approach is superior in terms of both lesion detectability and lesion definition. PMID- 17272044 TI - The affection of grey levels on mutual information based medical image registration. AB - Medical image registration is an active research field in medical image processing in the last two decades. One of the surveys of medical image registration is voxel-based method, which is generally considered as very accurate, almost fully automatic. The most efficient voxel-based method is maximization of mutual information (MI). In this paper, we will discuss the effects of rescaling intensity values of an image on MI method, and then compare the registration results and computation time of the same image pairs with different grey levels. We implemented series rigid registration of CT and MR image, in each registration, the intensity values of CT and MR images are linearly reseated to the same range. We adopt 5 different levels in our experiments, i.e. 256, 128. 64, 32 and 16 grey levels to exploit the affection of grey levels on MI based registration method. We also count the time cost on the calculation of single MI value and the whole registration procedure. Finally we reach this conclusion that the results become worse with the reduction of grey levels of the image, and rescaling the intensity values of the original images into [0,63] is an excellent tradeoff in brain registration by mutual information. PMID- 17272045 TI - Direction dependent projection fields for the fast DRR generation for medical 2D/3D registration. AB - The fast generation of digitally reconstructed radiographs is a prerequisite for intensity-based registration approaches. For our approach, extensive pre calculations are necessary that are saved in what we call a direction dependent projection field. The projection field approach reduces the complexity of the DRR calculation from O(n(3)) to O(n(2)). This paper develops the theoretical background and gives first examples of the application of projection fields for the 2D/3D registration of X-rays to CT data. PMID- 17272046 TI - A flexible registration framework for multimodal image data. AB - This paper describes a registration framework based on the insight segmentation and registration toolkit (ITK) which can be used for matching multimodal image data. Different target groups with individual needs and precognition are addressed. The framework offers tools for supporting different matching tasks in a clinical environment. A setup editor defines specific rigid or non rigid matching approaches and the appropriate parameters. Different metrics including a correlation metric, a difference metric and mutual information based metrics are available. Furthermore, a test series editor can be used to evaluate the selected setup. The evaluation results, which are expressed in statistical figures, trends and performance measures, can be visualized and used for an optimal adapted setup configuration. Tests for matching precision, quality and parameter adjustments are offered. For export and import of image data, the most frequently used file formats of clinical environments like DICOM and ANALYZE are supported. We demonstrate some registration examples which frequently occur in the neurosurgical routine of a University Hospital. PMID- 17272047 TI - Segmentation of bionano images for understanding cell dynamics. AB - The use of quantum dots (QDs) and molecular beacons (MBs) is a recent advance in the field of nanotechnology. These techniques have enabled us to detect a single molecule in a cell, which helps in understanding the dynamics of a cell. The success of these techniques depends on the accurate and efficient analysis of the imaging data these techniques produce. The processing involves--segmentation of the particles, colocalisation and their tracking over multiple frames in 2D and 3D space. In this paper we have used the active contour models: snakes and their variation--GVF (gradient vector field) snakes for segmentation of nano(QD) and cell(MB) images. The results of segmentation have been used to measure the degree of colocalisation for quantum dot images and the gene expression values for molecular beacon images. PMID- 17272048 TI - Mammogram object detection using dendronic image analysis. AB - Breast cancer can be treated with better patient outcomes and significantly lower costs if detected early. Using the spatial dendronic structure, image masks can be obtained, showing regions in the mammogram image corresponding to the breast and lead marker. The technique is robust to noise and placement of the breast within the image. The technique not only reduces the size of the region to be analysed, but also provides the dendronic structure of the breast in which stealth-like masses can be found more easily. PMID- 17272049 TI - Modeling susceptibility difference artifacts produced by metallic implants in magnetic resonance imaging with point-based thin-plate spline image registration. AB - Magnetic resonance imaging (MRI) suffers from geometric distortions arising from various sources. One such source are the non-linearities associated with the presence of metallic implants, which can profoundly distort the obtained images. These non-linearities result in pixel shifts and intensity changes in the vicinity of the implant, often precluding any meaningful assessment of the entire image. This paper presents a method for correcting these distortions based on non rigid image registration techniques. Two images from a modelled three-dimensional (3D) grid phantom were subjected to point-based thin-plate spline registration. The reference image (without distortions) was obtained from a grid model including a spherical implant, and the corresponding test image containing the distortions was obtained using previously reported technique for spatial modelling of magnetic susceptibility artifacts. After identifying the nonrecoverable area in the distorted image, the calculated spline model was able to quantitatively account for the distortions, thus facilitating their compensation. Upon the completion of the compensation procedure, the non recoverable area was removed from the reference image and the latter was compared to the compensated image. Quantitative assessment of the goodness of the proposed compensation technique is presented. PMID- 17272050 TI - Automatic detection of malignant tumors in mammograms. AB - Detection of malignant tumors at an early stage is an important first step in diagnosis of the cancerous regions in mammograms. Although many detection schemes have been presented, they are still not adequate to safely eliminate all risks. In this paper we propose classification schemes of unknown test mammograms using fractal analysis and spatial moments distributions as image processing techniques. Two classifiers will be used in conjunction with these techniques: a backpropagation neural network and a self-organizing map. Investigation of the histograms of the spatial moments at low orders shows that discrete image spatial moments cannot distinguish between benign and malignant mammograms. The two-stage backpropagation neural network and the one-stage self-organizing map both give detection rates of 70% and low false positive rates. With further preprocessing and optimization, the performance of these classifiers may be further improved. PMID- 17272051 TI - Ultrasound-based liver computer assisted surgery. AB - Ongoing research toward development of a computer-assisted, ultrasound-based software/hardware tool to improve instrument positioning in moving organs during minimally invasive abdominal surgery is presented. The main objective of this research is to calculate, in real time and without user intervention, the pre /intra-operative 3D/2D image misalignment due to patient respiration and the shift induced by the surgical instrument. Our methodology applied to the particular case of the liver, and partial results related to the image registration approach, based on organ segmentation and shape description, are presented. Preliminary results are highly encouraging. Among other benefits, use of this tool will increase surgeon confidence and improve surgery outcomes. PMID- 17272052 TI - A unified approach for lesion segmentation on MRI of multiple sclerosis. AB - Accurate determination of lesion volumes on brain MR images is hampered by the presence of a large number of false positive and negative classifications. A strategy that combines parametric and nonparametric techniques is developed and implemented for minimizing the false classifications. Initially, CSF and lesions are segmented using Parzen window classifier. Image processing, morphological operations, and ratio map of proton density (PD) and T2 weighted images are used for minimizing false positives. Lesions are delineated using fuzzy connectedness principle. Contextual information was used for minimizing false negative lesion classifications. Gray and white matter classification is realized using HMRF-EM algorithm. PMID- 17272054 TI - Breast segmentation in screening mammograms using multiscale analysis and self organizing maps. AB - Previously we presented an unsupervised self-organizing map (SOM) for segmentation of the breast region in screening mammograms. This study improves upon our earlier technique by (1) enhancing the detection of the breast region near the skin line, as well as (2) reducing the computational complexity. Contrary to the initial technique, the improved one exploits global image properties extracted at different scales. These properties were used to both generate the SOM training samples and obtain a preliminary segmentation. Subsequently, a multi-step strategy was implemented to automatically outline a wide band around the skin line for further analysis. This additional step reduces the computational complexity by focusing the analysis on the set of pixels that creates clinically the highest ambiguity. Specifically, the same (already trained) SOM was applied to classify the ambiguous pixels around the skin line. The study was performed on 400 screening mammograms from the digital database for screening mammography (DDSM). Visual examination of the segmentation results confirmed an improvement in the detection of the low-contrast region near the skin line. The performance was consistent regardless of mammographic view and/or breast density. Furthermore, the computational cost of processing can be reduced by up to 80% of the original value. PMID- 17272053 TI - Illumination-invariant change detection model for patient monitoring video. AB - Video recording is often conducted in the medical environment. Change detection provides a powerful tool to detect dynamic changes in the video to aid in monitoring and diagnosis. Illumination variation presents a typical problem for a change detection method to gain robustness. In this work, we describe a new method based on an illumination model and test statistics to reduce the sensitivity of detection to illumination changes. The effectiveness of this method is demonstrated by our experimental results. PMID- 17272055 TI - Extraction of tongue carcinoma using genetic algorithm-induced fuzzy clustering and artificial neural network from MR images. AB - A novel hierarchical image segmentation approach has been developed for the extraction of tongue carcinoma from magnetic resonance (MR) images. First, a genetic algorithm (GA)-induced fuzzy clustering is used for initial segmentation of MR images of head and neck. Then these segmented masses are refined to reduce the false-positives using an artificial neural network (ANN)-based symmetry detection and image analysis procedure. The proposed technique is applied to clinical MR images of tongue carcinoma and quantitative evaluations are performed. Experimental results suggest that the proposed approach provides an effective method for tongue carcinoma extraction with high accuracy and minimal user-dependency. PMID- 17272056 TI - Composite index for the quantitative evaluation of image segmentation results. AB - Medical image segmentation is one of the most productive research areas in medical image processing. The goal of most new image segmentation algorithms is to achieve higher segmentation accuracy than existing algorithms. But the issue of quantitative, reproducible validation of segmentation results, and the questions: What is segmentation accuracy?, and: What segmentation accuracy can a segmentation algorithm achieve? remain wide open. The creation of a validation framework is relevant and necessary for consistent and realistic comparisons of existing, new and future segmentation algorithms. An important component of a reproducible and quantitative validation framework for segmentation algorithms is a composite index that will measure segmentation performance at a variety of levels. We present a prototype composite index that includes the measurement of seven metrics on segmented image sets. We explain how the composite index is a more complete and robust representation of algorithmic performance than currently used indices that rate segmentation results using a single metric. Our proposed index can be read as an averaged global metric or as a series of algorithmic ratings that will allow the user to compare how an algorithm performs under many categories. PMID- 17272057 TI - Towards automatic reconstruction of dendrite morphology from live neurons. AB - The recent advent of optical imaging methods to capture both structural and functional data from living neurons holds the promise of improving our understanding of neuronal function. An important technical advance would be to use computer simulations to determine the optimal locations for high-speed functional imaging and electrical recording on an individual neuron. However, such simulations require a precise reconstruction of the dendritic morphology. Thus, the currently available time-consuming, semi-manual methods for morphological reconstruction prevent integration of cell-specific simulations into the experiments. Our work focuses on implementing a fast, robust method for extracting dendrite morphology from confocal or two-photon images to enable concurrent simulation and functional imaging of individual neurons. We discuss the current implementation of the morphological reconstruction, our approach to validation, and our initial results. PMID- 17272058 TI - Efficient segmentation framework of cell images in noise environments. AB - In this paper, we propose an efficient segmentation method that exploits local information for automated cell segmentation. This method introduces a new criterion function based on statistical structure of the objects in cell image. Each pixel is initially assigned to the most probable region and then the pixel assignment process is iteratively updated by a new criterion function until steady state is reached. We apply the proposed method to cervical cell images as well as the corresponding noisy images that are contaminated by Gaussian noise. The performance of the proposed method is evaluated based on the results from both normal and noisy cell images. PMID- 17272059 TI - Texture-based echocardiographic segmentation using a non-parametric estimator and an active contour model. AB - An accurate segmentation of cardiac cavities is necessary to assess cardiac function and to determine quantitative parameters. Several semi-automatic techniques have been tested to achieve this goal. In this work we propose an algorithm to segment cardiac structures, based on a robust pre-processing step that eliminates noise and extracts an initial frontier, together with a refined deformable model, that integrates edge confidence and texture information. Results show that a combination of a mean-shift filter with an active contour model is adequate for echographic images, especially when texture information is included. PMID- 17272060 TI - MRSI brain tumor characterization using wavelet and wavelet packets feature spaces and artificial neural networks. AB - Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique for assessing biochemical fingerprint of tissue composition. The need to differentiate between normal and abnormal tissues and determine type of abnormality before biopsy or surgery motivated development and application of MRSI. There are several technical reasons that make the brain easier than other organs to be examined with MRSI. This work presents our proposed methods and results for the analysis of the brain spectra of patients with three tumor types (malignant glioma, astrocytoma, and oligodendroglioma). After extracting features from MRSI data using wavelet and wavelet packets, we use artificial neural networks to determine the abnormal spectra and the type of abnormality. We evaluated the proposed methods using clinical and simulated MRSI data and biopsy results. The MRSI analysis results were correct 97% of the time when classifying the spectra of the clinical MRSI data into normal tissue, tumor, and radiation necrosis. They were correct 72% and 83% of the time when determining tumor types using the clinical and simulated MRSI data, respectively. PMID- 17272061 TI - Towards automated segmentation and classification of masses in mammograms. AB - This paper presents a straightforward approach to detecting and segmenting mammographic mass cores. The method utilizes adaptive thresholding applied to a contrast-enhanced version of the gray-scale mammogram, where the threshold is a function of the localized gray-level mean and variance. To assess the method's efficacy, it is applied to a database of 62 mammograms, each containing a suspicious mass (39 benign and 23 malignant). Each test case consists of a gray scale image and a binary image containing a radiologist segmentation of the mass. After segmentation, a variety of features are extracted, including several based on the normalized radial length, rubber band straightening algorithm, gray-level statistics, and patient age. Next, step-wise linear discriminant analysis is utilized for feature reduction and optimization. The same procedure is applied to the manually segmented masses. Analysis of the optimized features resulted in an ROC curve area of Az = 0.8796 and Az = 0.8719 for the automated and manually segmented masses, respectively. PMID- 17272062 TI - An adaptive approach for image subtraction. AB - Image subtraction is widely used in angiography as a means of highlighting differences induced by contrast agents. New knowledge of previously unsuspected causes of disease, in particular, secondhand smoke exposure, spurs interest in pushing the limits of early accurate diagnosis. Simple image subtraction induces artifacts causing problems for ensuing measurements and 3D reconstruction. Image registration techniques have been used to partially solve this problem. However, a complete registration is slow, and misregistration often occurs in images where bones are surrounded by vessels with similar image characteristics. We propose an approach based on the idea of global match followed by local refinements. In the global match, an image pair is aligned using a similarity measure so as to reduce overall difference. In the local refinements, localized displacements and deformations of tissue are handled by a combination of techniques: image registration, region growing, erosion, and dilation. This approach is fast compared to registration based image subtraction and it can find vessels abutting a bone. It is designed to be especially suitable for large cross-section image stacks. With additional vessel connectivity analysis between adjacent slices, the algorithm provides a good foundation for 3D vessel reconstruction. PMID- 17272063 TI - Diagnosis of articular cartilage using 3-D visualization and correlation with patient data. AB - Arthritis is a generic condition indicating inflammation of a joint. The most common form of arthritis is osteoarthritis. In this condition, the articular cartilage, the smooth gliding surface of the joint, is worn away. Image processing algorithms and advanced graphics techniques have been combined to detect wear in the articular cartilage. The cartilage was separated from the MRI data and image segmentation and thresholding algorithms have isolated the area of wear. A binary gradient masking technique was used to draw contours around the abnormality. A virtual three-dimensional model was developed showing different views, including a transparent view that enables one to see lesion inside the cartilage. PMID- 17272064 TI - 3-D optic disk reconstruction from low-resolution stereo images based on combined registrations and sub-pixel matching. AB - Three dimensional (3-D) visualization of optic disk surface is very useful for clinical application. It allows clinicians to measure the disk parameters more accurately and thus make the diagnosis easier. This work describes an automated 3 D optic disk reconstruction method from a pair of stereo images for which efficient steps including sparse-image registration, and dense-depth recovery are used. A combination of two registration methods is used to detect the sub-pixel correspondences. The proposed method takes the advantages of both the correlation method which is robust to noise and the feature based method on its accuracy. Only sparse match points are computed to speed up the processing and the sub pixel matching is used to overcome the problem of low resolution in the image. This is followed by the cubic interpolation to obtain the dense depths. The result is then smoothed and displayed as the final 3-D shape. PMID- 17272065 TI - Construction of an anatomically accurate geometric model of the forearm and hand musculo-skeletal system. AB - An anatomically accurate model of the forearm and hand musculo-skeletal system using finite element geometries is presented. Anatomical data has been digitized from the male Visible Human dataset to create meshes which accurately approximate each bone and muscle volume. Each muscle's anatomical structure has been accounted for via the topology of the initial mesh generation. Cylindrical muscles have been modeled using collapsed bicubic-linear elements, while more complex muscle topologies have required tricubic elements. Bifurcating muscle meshes combine 1D elements for the tendons and 3D elements for the adjoining muscle. The fitting process of each mesh to its dataset was carried out using a least-squares algorithm, to minimize the distances between the mesh and the data points. Sobelov smoothing constraints have been implemented to account for sparse and scattered data. The fitted forearm muscles contain 1085 nodes, 797 elements, and an average RMS error of 1.8207 mm; while the fitted hand muscles use 509 nodes, 274 elements, and an average RMS error of 1.1136 mm. Applications of the model as a framework for visualization of anatomical data relevant for biomedical and medical education are discussed. With mesh customization and further functional modeling this provides the basis for surgical training and functional development. PMID- 17272066 TI - Embedding EEG data on 3D head modeled using MRI data. AB - Current 3D head modeling techniques from magnetic resonance imaging (MRI) data fall short of what is needed by clinicians and scientists to study the head anatomy both in terms of accuracy and speed of rendering. This work proposes a novel direct modeling approach (DMA), which successfully and accurately models the 3D head with minimum processing requirements. A method for embedding the electroencephalogram (EEG) dipole source location into this modeled head is also demonstrated. The infomax algorithm is used for performing the independent component analysis (ICA) to obtain temporally independent stationary sources from multichannel EEG data. The dipole source location is then found by using the downhill simplex algorithm on the activation maps of each independent source. Finally a transformation matrix is derived that maps the dipole location onto the 3D head. PMID- 17272067 TI - Volumetric anatomical modeling from medical images. AB - Many clinical applications, such as surgical planning, require volumetric models of anatomical structures represented as a set of tetrahedra. A method of constructing anatomical models from medical images is presented. The method starts with a set of contours segmented from the medical images by a clinician and produces a model that has high fidelity with the contours. Unlike most modeling methods, the contours are not restricted to lie on parallel planes. The main steps are a 3D Delaunay tetrahedralization, culling of non-object tetrahedra, and refinement of the tetrahedral mesh. The result is a high-quality set of tetrahedra whose surface points are guaranteed to match the original contours. The key is to use the distance-map and bit-volume structures that were created along with the contours. The method is demonstrated on both computed tomography and 3D ultrasound data. Models of 170,000 tetrahedra are constructed on a standard workstation in approximately ten seconds. PMID- 17272068 TI - Visualization of anatomic covariance tensor fields. AB - The computation, visualization, and interpretation of brain variability remains a significant challenge in computational neuroanatomy. Current deformable registration methods can generate, for each vertex of a polygonal mesh modeling the cortical surface, a distribution of displacement vectors between the individual models and their average, which can be summarized as a covariance tensor. While analysis of anatomical covariance tensor fields promises insight into the structural components of aging and disease, basic understanding of the tensor field structure is hampered by the lack of effective methods to create informative and interactive visualizations. We describe a novel application of superquadric tensor glyphs to anatomic covariance tensor fields, supplemented by colormaps of important tensor attributes. The resulting visualizations support a more detailed characterization of population variability of brain structure than possible with previous methods, while also suggesting directions for subsequent quantitative analysis. PMID- 17272069 TI - Visualization of electrical current flow with a new streamline technique: application in mono- and bidomain simulations of cardiac tissue. AB - Mathematical modeling and computer-based simulation of electrical fields in the heart provide important insights into the cardiac electrophysiological behavior. Streamline based techniques are frequently applied for visualization of these electrical fields. In this work we present a new automated technique for placement of seed points of streamlines. The technique is based on a sequential optimization algorithm. In each step a set of random seed points is created. A single point of these is selected, which is optimal in such a manner that the distribution of density of streamlines fits best to the distribution of electrical current density. The iteration ends, when a pre-given number of streamlines was generated. Several examples illustrate the characteristic properties of the technique in electrical fields of small complexity. Additionally, results from a bidomain simulation of excitation propagation are visualized. PMID- 17272070 TI - Digital Chinese human dataset and its applications. AB - This paper presents some image processing methods of virtual Chinese human (VCH) dataset, including the multislice registration, reduction of noise and artifacts and segmentation techniques. A new hybrid volume render method based on parallel computing is also introduced for high resolution visualization of the large dataset of VCH. The results of visualization show that the methods work well and can be used for high resolution visualization of VCH dataset. PMID- 17272071 TI - A haptic-based system for medical image examination. AB - This paper presents a haptic-based simulator for training of radiology residents and sonographers. The system consists of a force feedback haptic device providing means to interact in real-time with volumetric images of a virtual patient, captured pre-operatively from several subjects. The training system allows trainees to develop radiology techniques and knowledge of the patient's anatomy with minimum practice on live patients, or in places or at times when radiology devices or patients with rare cases may not be available. The haptic interface guarantees position correspondence between the operator's hand and a virtual probe position that slices medical volume sets in the plane of the probe. Thus the simulated procedure becomes nearly identical to the real examinations at the hospital. Different configurations of the system are implemented and presented. Future potential applications for the system are discussed as well. PMID- 17272072 TI - Color coding for visualization of the directional information of DTI. AB - A new color coding scheme which can fully retrieve the directional information of diffusion tensor image (DTI) with maximum use of the color space is proposed and implemented. This new scheme overcomes the loss of directional information in conventional schemes and easy to implement. Comparison between the new scheme and the conventional color coding method are presented using the DTI data of human brain. PMID- 17272073 TI - A method of extraction and graphical presentation of diaphragms for an observation system with an intuitive control. AB - The observation of movement of diaphragm is one of important methods for diagnosis of lung diseases. So, we have been developing an observation system which generates a movie of pseudo solid images using numerous sagittal and frontal MRI images and the movie on a flat panel monitor. And also the direction of the solid images can be changeable dynamically by operator's tilting its monitor, which means the intuitive control. We refined our observation system and developed a method to extract a diaphragm boundary and a new presentation to display the boundary of a diaphragm and body outlines to observe and discriminate their movement. PMID- 17272074 TI - Construction of a frameless camera-based stereotactic neuronavigator. AB - We built an infrared vision system to be used as the real time 3D motion sensor in a prototype low cost, high precision, frameless neuronavigator. The objective of the prototype is to develop accessible technology for increased availability of neuronavigation systems in research labs and small clinics and hospitals. We present our choice of technology including camera and IR emitter characteristics. We describe the methodology for setting up the 3D motion sensor, from the arrangement of the cameras and the IR emitters on surgical instruments, to triangulation equations from stereo camera pairs, high bandwidth computer communication with the cameras and real time image processing algorithms. We briefly cover the issues of camera calibration and characterization. Although our performance results do not yet fully meet the high precision, real time requirements of neuronavigation systems we describe the current improvements being made to the 3D motion sensor that will make it suitable for surgical applications. PMID- 17272075 TI - Characterizing the attenuation and/or saturation effect of the acoustic scanner noise in auditory event-related functional magnetic resonance imaging. AB - The analysis of event-related functional magnetic resonance imaging when presenting auditory stimuli and/or investigating auditory cortex and related areas is hindered by inherent acoustic scanner noise (ASN), which can alter the properties of the acquired time-series data. Therefore, it is necessary to account for ASN in the analysis, and one step towards this goal is to characterize the attenuation and/or saturation effect of the hemodynamic response due to ASN. Towards this end, this study examined how the effect of ASN is dependent on repetition time (TR) and the inter-stimulus interval (ISI), two experimental parameters that affect the acoustic signal-to-noise ratio of the experimental paradigm. Results indicate that a decrease in TR (e.g., 6 s to 1.5 s) results in an increase in saturation and an attenuation of the estimated hemodynamic response peak with respect to the baseline signal level. There was no statistical difference in peak response between the two ISI values used, 12 s and 18 s. PMID- 17272076 TI - Analysis of brain activation by visual and auditory stimulation after visual and auditory simultaneous stimulation using F-MRI. AB - It is said that the auditory spatial perception is strongly affected by visual cues, and when auditory and visual stimulation are given form different positions simultaneously, the source position of sound is mislead to the direction of visual stimulation. The purpose of this study is analyzing the brain response on f-MRI by simultaneous stimulation of auditory and visually sensors. f-MRI of some subjects were measured by using simultaneous stimulation, and the results of these experiments were analyzed and assessed. From these experiments, following characteristics became clear. 1) Simultaneous stimulation activate each cortex stronger than the results of single stimulation. 2) After giving auditory and visual stimulus as preliminary stimulation to subject, one type of stimulus was given to the subject. From this stimulation, both cortex were activated. This activation was weaker than the time of actually giving simultaneous stimulus. From investigation of these results, it seems that the relationship between auditory and visual cortex become clear. PMID- 17272077 TI - Clustering of fMRI data for activation detection using HDR models. AB - The aim of this work is to perform parametric estimation and detection of activation in fMRI data. The proposed procedure is a segmentation algorithm where clustering is based on estimated parameters for a chosen hemodynamic response (HDR) model. These parameters are estimated for each individual voxel by performing a weighted least-squares nonlinear curve fit to its time series. The parameters are used to decide which voxels are candidates for activation. A segmentation algorithm is executed on a subset of the image voxels, selected based upon fitting parameters. Our procedure will yield activation maps constructed from possibly 2-D (i.e., multi-voxel) regions of activation as opposed to identifying voxels based on individual voxel statistical significance, followed by merging into regions. The approach is intended to reduce false detections, producing "cleaner" activation results without resorting to filtering techniques that may sacrifice spatial resolution. PMID- 17272078 TI - DT-MRI regularization using 3D nonlinear gradient vector flow anisotropic diffusion. AB - In DT-MRI, diffusion-weighted multislice echoplanar images (EPIs) are processed to represent water diffusion characteristics as a diffusion tensor, reflecting the amount of diffusion in 3D. However imaging quality is generally compromised by several factors including the number of imaging slices, averages, diffusion sensitization steps (b-values), voxel size, and gradient directions, resulting in suboptimal SNR. In this study, we focus on improving imaging quality and SNR by denoising and reducing systematic and random errors through nonlinear anisotropic regularization. The raw EPIs are directly regularized through a newly proposed nonlinear anisotropic diffusion regularization method in 3D utilizing the gradient vector flow fields and its performance is compared to conventional 2D and vector-valued 2D anisotropic regularization methods. The effects of these variants of anisotropic regularization are examined through the maps of color coded fractional anisotropy and tracked neural fibers. The results show that DT MRI regularization using the proposed 3D anisotropic diffusion significantly improves the quality of fiber tracking and diffusion indices such as fractional anisotropy. PMID- 17272079 TI - The effects of water diffusion and laminar flow on velocity-selective arterial spin labeling. AB - Arterial spin labeling (ASL) has been developed as a useful tool for measuring local tissue perfusion with magnetic resonance imaging (MRI). In contrast to conventional ASL that spatially labels spins, velocity-selective ASL (VS-ASL) tags spins on a basis of flow velocity. Using a 90 degrees-180 degrees-90 degrees radiofrequency pulse train in combination with flow-sensitive gradients, VS-ASL can potentially generate tags that are very close to the imaging plane and whereby avoid the main error source of conventional ASL techniques coming from T1 relaxation during inflow time (TI). In this study, computer simulation was used to evaluate the diffusion effect upon the tag distribution during the VS process. The change of tag amount caused by water diffusion was found to be less than 5%. Considerations of the velocity threshold (Vcut) were addressed as well. Large Vcut incurs longer delay for the delivery of tags, compromising the advantage of VS-ASL. A Vcut below 5 cm/s is recommended on the premise of proper CSF suppression. PMID- 17272080 TI - Testing the distribution of nonstationary MRI data. AB - An accepted model for MR image noise is a Gaussian distribution in the real and imaginary components of the complex valued image. We investigated a procedure for validating this model through repeated hypothesis testing. The procedure is relatively straight forward for the situation in which an image contains only noise. However there is an additional challenge when a signal component is added because the signal intensities tend to drift over time. We therefore extend the noise model by considering a time-varying mean, and then implement a procedure for modeling, estimating, and removing the drift component in order to test the underlying noise distribution. The results demonstrate consistency with the proposed noise model. PMID- 17272082 TI - Supervised clustering approach to form functional images in positron emission tomography. AB - The aim of this study is to investigate the availability of supervised statistical clustering algorithm for image-based model analysis in positron emission tomography or nuclear medicine to form a functional image. Voxel-by voxel model analysis can derive functional images, but bad statistic property in voxel-based PET data and huge number of voxels prevent to realize practical algorithm to form parametric images. In this study, supervised clustering is applied to categorized PET data. The shape of tTAC is projected in multidimensional feature space, and noise propagation is modeled as multivariate Gaussian in the space. Simulation study shows that the estimates by the proposed algorithm was identical to the true values. And a clinical image of has physiologically acceptable aspect. We can conclude that supervised clustering sachem has potential to realize practical algorithm for voxel-based model analysis in PET. PMID- 17272081 TI - A pilot study of the reading processes combining reading-related potentials (RRPs) and fMRI. AB - Aim of this work is to describe temporally and spatially the activation of the cerebral areas involved in reading processes by combining fMRI and reading related potentials (RRPs). RRPs and fMR images were recorded in separate studies during a specifically designed experimental procedure. The protocol consisted of three visual tasks of increasing complexity. In the first two tasks subjects were asked to passively watch at letters and symbols respectively without making any effort in reading or articulating silently them. In the third task subjects were asked to read aloud letters appearing on a screen at a rate of 0.5 Hz. 7 young healthy subjects participated in the experiment. The analysis of RRPs highlighted the following results. During non-alphabetic symbols presentation the amplitude of the potentials was lower in comparison to presentation of letters. Reading aloud generated RRPs of greater amplitude than implicit reading. The analysis of fMRI scans revealed that the visual presentation of both letters and symbols produced similar activation of primary visual areas. Besides these areas, reading aloud activated the motor and pre-motor cortices and the left anterior temporal lobe. The combined analysis of RRPs and fMRI characterizes both temporally and spatially the development of reading processes. PMID- 17272083 TI - Characterizing the amplitude and spatial extent of the cortical response in auditory cortex to acoustic scanner noise generated during echo-planar image acquisition in functional magnetic resonance imaging. AB - Acoustic scanner noise produced during event-related functional magnetic resonance imaging (ER-fMRI) studies can hinder auditory fMRI research analysis by altering the properties of the acquired time-series data. Given the desire to obtain the most accurate results possible using ER-fMRI experiments, this study seeks to characterize the amplitude and spatial extent of the auditory fMRI cortical response, in isolation, generated by the acoustic scanner noise associated with echo-planar acquisition. Results from this study indicate that the pure cortical response is non-trivial, is comparable to a standard hemodynamic response function, and should be accounted for in analysis using ER fMRI models. PMID- 17272084 TI - EEG source localization using differential evolution method. AB - Differential evolution (DE) method is used in This work to solve the EEG source localization problem based on equal current dipole model. The single dipole sources with four-shell concentric sphere model are reconstructed. Our simulations demonstrate that DE algorithm is robust in obtaining high quality reconstruction for EEG problems with single current dipole sources. PMID- 17272085 TI - Solving the three-dimensional EIT forward problem using finite element method. AB - Electrical impedance tomography (EIT) is a newly developed technique by which impedance measurements from the surface of an object are reconstructed into impedance image. But in the initial stage, the EIT problem is regarded as the two dimensional EIT problem, which ignores too much important information and makes it can't give the exact spatial information of the place where the impedance has changed because of some diseases. We pay much attention to the three-dimensional EIT and here the finite element method (FEM) is used. Tetrahedron is used in the subdivision. The potential of each node can be given by the solution of the forward problem, which is the reference of the EIT inverse problem, and it is proved close to the analysis solution. PMID- 17272086 TI - Semi-automatic segmentation of the endocardial boundary in intracardiac echocardiographic images. AB - Intracardiac echocardiograpby (ICE) has been employed in guiding clinical interventional procedures. ICE could also be useful for 3-D anatomical and functional imaging of the heart. In this regard, we developed and tested a method to semi-automatically determine the endocardial boundary in multiple tomographic ICE images. Compared to manual segmentation, we found that semi-automatic segmentation of the endocardial boundary in ICE images was feasible and enabled accurate and efficient reconstruction of 3-D geometry of the heart cavity. PMID- 17272087 TI - Real time high spatial-temporal resolution flow imaging with spiral MRI using auto-calibrated SENSE. AB - A novel spiral phase contrast technique was developed for high temporal and spatial resolution imaging of blood flow without cardiac gating. Spiral sampling of k-space has excellent flow properties and acquisition speed. Parallel imaging using the coil sensitivity maps can be used to reduce the imaging duration at the cost of SNR. An auto-calibrated spiral sensitivity encoding method is introduced and used for reconstruction of phase contrast images. Phase estimation for a simulated phantom using data from various acceleration rates was compared to the true phase map. To study the accuracy of the flow estimate with parallel image reconstruction, a high resolution cardiac gated experiment was performed and a subset of under-sampled data were reconstructed. The real-time experiments were performed to measure blood velocity in the ascending aorta and through the aortic valve with high spatial and temporal resolution. Temporal resolution of the flow images was improved by a factor of at least three with no cardiac gating signal with preserved spatial resolution. The results demonstrate the potential of using the technique for real-time flow imaging with improved spatial and temporal resolution. PMID- 17272089 TI - Evaluation of three different kinetic models for use with myocardial perfusion MRI data. AB - Coronary artery disease (CAD), a leading cause of death in the US and worldwide, can be effectively diagnosed and assessed using non-invasive myocardial perfusion MRI. Tracer kinetic models play a crucial role in the analysis and quantification of perfusion. In this work, we evaluate the performance of 3 different kinetic models used to analyze perfusion: (a) a modified 2-compartment model (b) the Johnson-Wilson (JW) model and (c) a modified JW model. We hypothesized that three different models would give statistically different results and that the modified JW model would be better than the other two because it would most closely model the underlying physiological processes. Results indicate that the models are statistically different from each other but the 2-compartment model is more stable than both models (b) and (c) and that the modified JW model is the most sensitive to ischemia as compared to the others. PMID- 17272088 TI - An accurate and reproducible scheme for quantification of coronary artery calcification in CT scans. AB - The coronary artery disease is a major cause of deaths in the western world. One indicator for coronary artery disease (CAD) is coronary artery calcification (CAC). An accurate and reproducible scheme is desired to monitor the progression of patient's coronary calcification in follow-up studies. Traditional approaches for CAC estimation lack to provide accurate and reproducible results. In This work, a new adaptive and stochastic 3D method has been proposed by employing a modified expectation-maximisation (MEM) algorithm. It is less sensitive to partial volume effects, motion effects, slice thickness and low dose. Accuracy of the proposed method was measured by a cardiac CT stationary phantom containing 6 calcium inserts of predetermined size and density that were scanned 90 times using 15 different protocols based on slice thickness and radiation. Reproducibility was measured in 35 patients who were each scanned twice with the patient being repositioned before the second scan. Compared with the Agatston based method, it is shown that the proposed algorithm gives better results in terms of accuracy and reproducibility. PMID- 17272090 TI - Elastically deformable model-based motion-tracking of left ventricle. AB - The motion of the myocardium is a sensitive indicator of many types of heart disease. Quantitative characterization of this motion is essential for the accurate diagnosis and treatment of heart disease. Although several magnetic resonance imaging (MRI) techniques, such as tagged MRI and phase contrast MRI, provide noninvasive tools to obtain correlation of the position of points within the myocardium between images taken at subsequent time phases, the accurate tracking of the movement of these points remains a challenge due to the relatively low out-of-plane resolution of these imaging techniques. A motion tracking method based on elastic deformation estimation of a deformable model has been developed to track the three-dimensional motion of the myocardium. Elastic deformation estimation is performed on phase contrast MRI data by balancing the deformation potential energy of a deformable model and the potential energy derived from integrating velocity values of myocardial tissue points. The advantage of this method is that it can provide a physically plausible yet computationally efficient framework for cardiac motion tracking. To assess the proposed method, the motion of a normal human left ventricle (LV) was tracked throughout the entire cardiac cycle, and a quantitative strain analysis of the motion of the LV was carried out from end diastole to end systole. The results showed that the strain measurements were generally found to be consistent with previously published values. PMID- 17272091 TI - Fluoroscopic navigation to guide RF catheter ablation of cardiac arrhythmias. AB - Severe disorders of the heart rhythm that can cause syncope or sudden cardiac death (SCD), can be treated by radio-frequency (RF) catheter ablation. The precise localization of the arrhythmogenic site and the positioning of the RF catheter over that site are problematic: they can impair the efficiency of the procedure and are time consuming (several hours). Our approach consists of integrating fluoroscopic and electrical data from the RF catheters into the same image so as to better guide RF ablation, shorten the duration of this procedure and increase its efficacy. PMID- 17272092 TI - The next generation EKG--in vivo demonstration of noninvasive electrocardiographic imaging during normal sinus rhythm. AB - Noninvasive, in vivo, reconstruction of epicardial electrical activity is needed to help better study, understand, and treat electrical rhythm abnormalities. Here, a new method for noninvasive electrocardiographic imaging is used to reconstruct epicardial potentials in vivo during normal sinus rhythm. This method used measured body surface potentials (BSPMs) and the relative geometry between the body surface and epicardial surface from computed tomography (CT) to reconstruct in vivo epicardial potentials during normal sinus rhythm. The reconstructed epicardial potentials correlated qualitatively with those expected for various aspects of normal sinus rhythm (NSR). This study shows that noninvasively reconstructed epicardial potentials could provide useful information on the electrical activity of the heart during normal activation and repolarization sequences not otherwise available. PMID- 17272093 TI - Simulation data mapping in virtual cardiac model. AB - Although 3D heart and torso model with realistic geometry are basis of simulation computation in LFX virtual cardiac model, the simulation results are mostly output in 2D format. To solve such a problem and enhance the virtual reality of LFX virtual cardiac model, the methods of voxel mapping and vertex project mapping were presented. With these methods, excitation isochrone map (EIM) was mapped from heart model with realistic geometry to real visible man heart model, and body surface potential map (BSPM) was mapped from torso model with realistic geometry to real visible man body surface. By visualizing in the 4Dview, which is a real-time 3D medical image visualization platform, the visualization results of EIM and BSPM simulation data before and after mapping were also provided. According to the visualization results, the output format of EIM and BSPM simulation data of LFX virtual cardiac model were extended from 2D to 4D (spatio temporal) and from cardiac model with realistic geometry to real cardiac model, and more realistic and effective simulation was achieved. PMID- 17272094 TI - Multi-lead ECG electrode array for clinical application of electrocardiographic inverse problem. AB - Methods for noninvasive imaging of electric function of the heart might become clinical standard procedure the next years. Thus, the overall procedure has to meet clinical requirements as easy and fast application. In this study we propose a new electrode array which improves the information content in the ECG map, considering clinical constraints such as easy to apply and compatibility with routine leads. A major challenge is the development of an electrode array which yields a high information content even for a large interindividual variation in torso shape. For identifying regions of high information content we introduce the concept of a locally applied virtual electrode array. As a result of our analysis we constructed a new electrode array consisting of two L-shaped regular spaced parts and compared it to the electrode array we use for clinical studies upon activation time imaging. We assume that one side effect caused by the regular shape and spacing of the new array be that the reconstruction of electrodes placed on the patients back is simplified. It may be sufficient to record a few characteristic electrode positions and merge them with a model of the posterior array. PMID- 17272095 TI - A new ECG obtained from MCG-recordings. AB - A computational study of a magneto-electrocardiogram (magneto-ECG) and a correlative locus of the total current dipole vector map are presented. Unlike the ordinary electrocardiogram (ECG), the magneto-ECG is the solution to the inverse problem of electrocardiograph), which is calculated with the magnetic field signals recorded at 36 locations of a human heart surface. Using this method we investigated 6-lead magneto-ECG, the correlative locus of the total current dipole vector during a cardiac cycle and the current density distribution map. We find that the magneto-ECG and the correlative locus of the total current dipole vector map reveal not only the properties of P-wave, QRS-wave, T-wave similar to the common ECG, but also additional information about the electrophysiological activity of the heart. We anticipate that the magneto-ECG and the locus of the total current dipole vector map may avail the early diagnosis of cardiac diseases. PMID- 17272096 TI - Cell-based biosensors for single cell monitoring and drug analysis. AB - Cell-based biosensors incorporate cells as sensing elements that convert a change in immediate environment to signals conducive for processing. It characterizes with high sensitivity, excellent selectivity and fast response. Cell-based biosensors have been implemented for a number of applications ranging from pharmaceutical screening to environmental pollutant detection. This work demonstrate a novel cell-based biosensor following the principle of light addressable potentiometric sensor and field effect transistor for detecting the action potential of single living cell under drugs. The experimental results agree with our expectation. PMID- 17272097 TI - Direct detection of bacterial genomic DNA using gold nanoparticle probes. AB - The molecular probes and associated instrumentation necessary to perform genetic analyses are typically expensive, complex, and prone to error. While techniques such as real-time polymerase chain reaction (PCR) and gene expression analysis have provided a wealth of information previously unattainable, their utility in clinical diagnostics has yet to be realized due to the aforementioned limitations. Nanosphere Inc. has developed a gold nanoparticle-based platform for sequence specific DNA detection that is well-suited for clinical diagnostics due to its cost-effectiveness, simplicity, and accuracy. Thirteen nanometer gold nanoparticle probes, stabilized by a shell of oligonucleotides using proprietary attachment chemistries, enable highly sensitive and specific detection of bacterial genomic DNA sequences without synthetic amplification techniques on a glass array. After silver staining, light scattered by the nanoparticle probes is collected with robust, cost-effective instrumentation. It is the unique features of Nanosphere's detection methodology that provide the necessary steps forward to allow for genetic analyses to become part of routine clinical diagnostics. PMID- 17272099 TI - Characterization and optimization of an optical DNA hybridization sensor for the detection of multi-drug resistant tuberculosis. AB - The development of an optical DNA hybridization biosensor based on ruthenium electrochemiluminescence (ECL) was designed to detect DNA hybridization, using the detection of specific DNA sequences, which are indicative for antibiotic resistant strains of Mycobacterium tuberculosis as a model. The development of the sensor involved the characterization and optimization of the individual elements of the biosensor. Using this approach it was possible to ensure that the complete biosensor system was optimized to its maximum sensitivity for the electrochemiluminescent optical signal, which is produced during the DNA hybridization event. The transduction element used in this work is a solid-state silicon PIN photodiode. The miniaturization of the optical element to 5 mm(2) and smaller has made it possible to integrate the optical element internally as part of the biosensor scheme. Ruthenium ECL is a chemiluminescent reaction that is initiated by electrical stimulation. Photolithographic techniques were used to deposit and pattern gold electrodes directly onto the surface of the PIN photodiodes for the initiation of the ECL reaction. The gold electrodes also act as a biological support layer for DNA immobilization via thiol -gold linkage chemistry. The characterization and optimization of the individual components of this biosensor have allowed us to fabricate a miniaturized and integrated system that is compatible with a flow-through system. PMID- 17272098 TI - Detection of dielectrophoretic driven passage of single cells through micro apertures in a silicon nitride membrane. AB - Silicon (Si) microstructures are fabricated comprising a micro-aperture (10-25 microm) in a 1.2 kA silicon nitride membrane connecting two microfluidic compartments. Dielectrophoretic forces are created on-chip, which guide the passage of single CHO cells through the microaperture. When a cell dielectrophoretically traverses the aperture, there is a decrease in the background ionic current. These current fluctuations are recorded under varying cell concentrations, micro-aperture sizes, and applied voltages. This work shows the feasibility of building silicon-based bioparticle detectors with nanoscale apertures for sensing the translocation of cells, proteins, and even single stranded DNA. PMID- 17272100 TI - Design and fabrication of a silicon microreactor for DNA amplification. AB - A silicon microreactor consisting of an integrated heater, temperature sensor and thermal isolation chamber has been described. The thermal characteristics of the device have been studied by computer simulation and a rapid heating rate (20 degrees C--95 degrees C in less than 2 s) has been achieved. The fabrication process, consisting of microelectromechanical systems (MEMS) fabrication techniques has been established. The design features of this device, in particular the integrated heater and temperature sensor and the thermal isolation chamber allows fast heating/cooling rates and therefore enables efficient thermocycling suitable for DNA amplification. PMID- 17272101 TI - pH sensor using nanoelectrodes in organic semiconductor. AB - A new pH sensor using nanoelectrodes in organic semiconductor P3HT (regioregular poly(3-hexylthiophene)) has been designed, fabricated and characterized in this work. In this sensor, the organic semiconductor is directly exposed to pH sample solution, and an electrical field is applied to drive the protons in the solution to the polymer surface. The accumulated protons at the interface between organic semiconductor and solution change the electron density at organic semiconductor surface, so that the conductivity of the organic semiconductor film is modulated. In order to improve the sensitivity of sensor, P3HT is coated on the interdigitated array nanoelectrodes, and the conductivity of P3HT between two bands of electrodes is measured for pH characterization. A good conductivity modulation by the proton concentration or pH value is shown in the sensor testing. PMID- 17272102 TI - Surface plasmon resonance device with dielectric mirror for biochemical sensing. AB - We have reported a novel design of surface plasmon resonance (SPR) device, which uses alternative dielectric layers to enhance the SPR signal quality and modulate its resonant position. Admittance loci method of thin film design has been used in the design of such a device. The fabricated device results in a calibration curve, y= 0.124 x + 62.39 (R 2=0.99) of different glucose concentrations. PMID- 17272104 TI - Speed improvement of a pathogenic micro-organism population detection with LAPS system by a magnetic bead separation and a pH detection. AB - In this paper, a magnetic bead based immobilization method and pH detection method is applied to the LAPS (light addressable potentiometric sensor) system to detect a pathogenic micro-organism population. Magnetic beads are very small, superparamagnetic particles (0.8 approximately 5.0 microm in diameter) that are able to sustain a magnetic domain under excitation and do not exhibit residual magnetization when the external field is removed. By using magnetic beads as an immobilization method, other bulky and complex method can be alternated. To verify the method, an urease labeled anti-salmonella typhimurium antibody is used to detect a pathogenic micro-organism( S. typhimurium ) population by a bias voltage maximum slope detection. PMID- 17272103 TI - The development of biosensor with imaging ellipsometry. AB - The concept of biosensor with imaging ellipsometry was proposed about ten years ago. It has become an automatic analysis technique for protein detection with merits of label-free, multi-protein analysis, and real-time analysis for protein interaction process, etc. Its principle, and related technique units, such as micro-array, micro-fluidic and bio-molecule interaction cell, sampling unit and calibration for quantitative detection as well as its applications in biomedicine field are presented here. PMID- 17272105 TI - Soft mold-dry etch: a novel hydrogel patterning technique for biomedical applications. AB - This paper introduces a novel patterning technique for environmentally sensitive hydrogels using a combination of soft mold and dry etch. This method alleviates the need for photoinitiators used in conventional approaches and is applicable to a broad range of hydrogels. This technique is also compatible with the traditional microfabrication methods thus allowing the integration of hydrogels with microelectronics and MEMS microstructures. Hydrogels of different shapes and sizes were patterned in a batch scale (wafer-level) with resolutions of up to 2.5 microm. The patterned pH-sensitive hydrogels with micron-sized dimensions were able to respond within seconds. Deposited aluminum thin films on top of hydrogel microstructures was used to fabricate environmentally sensitive free standing micro-mirrors with a vertical displacement sensitivity of 7 microm/pH at pH 5.0. These structures open the possibility of fabricating on-chip photonic-based hydrogel microsensors. PMID- 17272106 TI - Needle-type multi-electrode array fabricated by MEMS technology for the hypodermic continuous glucose monitoring system. AB - A needle-type multi-electrode array for the hypodermic continuous glucose monitoring sensor was fabricated using MEMS technology. The developed multielectrode sensor has 4 electrodes of two working(Pt) electrodes, one counter(Pt) electrode, and one reference(Ag/AgCl) electrode. Two working electrodes are for the enzyme and nonenzyme electrodes which measure glucose concentration and the background current (I(0)), respectively. The developed integrated sensor system is adequate to accomplish our prereported new two-point calibration method using only one-point sample measurement. Results of in vitro performance test are also provided. PMID- 17272108 TI - A low-profile three-dimensional neural stimulating array with on-chip current generation. AB - This paper describes a low-profile silicon microelectrode array for selectively stimulating in the central nervous system. The array consists of a number of 64 site 8-channel planar CMOS probes, a platform to support the probes on the cortical surface, spacers to hold the probes orthogonal to the platform, and a hybrid chip for platform address decoding. It features integrated circuitry with on-chip current generation to deliver biphasic currents from -127 microA to +127 microA to selected sites with 1 microA resolution and fold-down structures to reduce the vertical rise above the cortex for chronic implants. The output stimulating current has a differential nonlinearity of less than 0.8LSBs and a biphasic mismatch of less than 0.23LSBs. The average power dissipation to generate full-range biphasic pulses with pulse widths of 100 micros at a repetition rate of 500 Hz is about 97 microW per channel. The probes and the hybrid chip are fabricated in a 3 microm, p-sub/n-epi/p-well 2P/1M micromachined CMOS technology; the other structures use a simplified passive process. PMID- 17272107 TI - Microwave transmission line dielectric probe to detect biomolecular surface interactions. AB - A probe was developed to detect biomolecular binding events at a liquid-solid interface in the microwave regime in real time and without using fluorescence labels. The probe consists of a coplanar transmission line (CTL) fabricated on a glass slide that can detect dielectric changes in close proximity of the interface. The CTL geometry concentrates the electric flux density in the gap region between the signal and ground electrodes and makes it very sensitive to permittivity changes at the liquid-solid interface. The probe operation was demonstrated by immobilizing protein A on the glass surface and detecting rabbit IgG molecules in a flow channel. The sensitivity was conservatively estimated to be 100 pg/mm(2). PMID- 17272109 TI - FSH biosensor to detect postpartum ovarian recrudescence. AB - Preliminary evidence of FSH suppression as a marker of postpartum ovarian recrudescence is presented. Falling FSH concentration in response to ovarian follicular estrogenic secretory activity apparently signals the reestablishment of menstrual cycles. We propose to investigate further this phenomenon with the development of a portable FSH biosensor. The FSH biosensor design is based on SPR and biological thin-film technologies and is incorporated as a key element of the fertility information appliance. It is possible that the device could be a useful natural family planning tool, especially during the return to fertility after childbirth. PMID- 17272110 TI - The effect of the substrate on the extracellular neural activity recorded micromachined silicon microprobes. AB - The influence of a highly-doped silicon substrate on the neural activity recorded by thin-film microelectrode arrays has been explored using top, back, and double sided recording sites. Probes having shank widths from 25-50 microm and site spacings (in depth) from 20-40 microm were used. The realization of back-looking and double-sided sites requires one mask in addition to the normal 8-mask passive probe process. Back-looking sites record as well as top sites even though separated by only a few microns from the surrounding silicon substrate, indicating that the substrate acts as an insulator and does not shunt local current from the extracellular space. On wide substrates, back-looking sites can thus be used to ensure a spherical recording field. As the substrate width is scaled to dimensions of a few microns, it should leave the extracellular field relatively undisturbed while providing mechanical support and suppressing crosstalk. PMID- 17272111 TI - Modeling magnetic catheters in external fields. AB - We develop a mechanical model for catheters and other interventional devices which are steered by externally applied magnetic fields. Each device contains a permanent magnet near its distal tip. The external magnetostatic field, whose direction and magnitude can be selectively varied, is applied to the vicinity of the tissue where the medical procedure is being performed, in order to orient the catheter tip. At the same time, the length of the catheter is varied by a motorized advancer. The position and orientation of the catheter tip is determined in real-time by electromagnetic means. This information can be fed into a closed-loop control algorithm which would decide how to change the magnetic field and the catheter length. The model includes closed-form solutions of the equilibrium equations, which facilitates accurate estimation of the catheter configuration and the contact force. Once the device is at a target point, the control algorithm can modify the contact force applied to the tissue. Common applications include navigation inside the heart and coronary vessels, electrophysiology (atrial fibrillation, flutter and tachycardia, ventricular tachycardia, etc.) and interventional cardiology (angioplasty). PMID- 17272112 TI - Tri-axial plantar pressure sensor: design, calibration and characterization. AB - A novel tri-axial plantar pressure sensor has been developed. This sensor simultaneously measures vertical plantar pressure and anterior-posterior and medial-lateral shear plantar pressures utilizing a central post, four parallel plates, and a commercial miniature pressure transducer. As a subject walks over the sensor, the central post is deflected and the shear pressures are measured utilizing capacitive sensing technology. The miniature pressure transducer (MPT) is simultaneously loaded to measure the vertical pressure. Each individual tri axial plantar pressure sensor has the capability of measuring shear forces ranging from 0 to 15 N and vertical pressures ranging from 0 to 28 MPa. The shear component of the tri-axial pressure sensor has a sensitivity of 1.3 mV/g, a non linearity of 8.3 %, and hysteresis of 7.3 %. The commercial vertical MPT has a sensitivity of 220 nv/V/psi, a non-linearity of 0.094%, and a hysteresis of 0.567%. An array of individual tri-axial plantar pressure sensors in the form of a platform will be developed to measure plantar pressure in patients. This pressure platform is placed on the surface of a walkway and is suitable for barefoot walking trials. PMID- 17272113 TI - Drosophila flight force measurements using a MEMS micro force sensor. AB - This paper reports a MEMS micro force sensor with differential tri-plate comb drives. Bulk micromachining is utilized to construct the high aspect ratio devices. The sensor has a high sensitivity, good linearity, and a large bandwidth, which are required for characterizing flight behavior of fruit flies (Drosophila). The technique allows instantaneous flight forces, which result from the combination of aerodynamic forces and inertial forces, to be captured in real time, providing valuable data for understanding flight biomechanics in Drosophila. The integration of the MEMS micro force sensors into flight simulators will provide a novel and efficient experimental paradigm for further insect neurophysiology studies. The potential impact of this research extends beyond gathering flight data on Drosophila by demonstrating how MEMS technology can be used to provide valuable tools for biological investigations. PMID- 17272114 TI - An apparatus for high throughput nanomechanical muscle cell experimentation. AB - An array of independent muscle cell testing modules is being developed to explore the mechanics of cardiac myocytes. The instrument will be able to perform established physiological tests and utilize novel system identification techniques to measure the dynamic stiffness and stress frequency response of single cells with possible applications in the pharmaceutical industry for high throughput screening. Currently, each module consists of two independently controlled Lorentz force actuators in the form of stainless steel cantilevers with dimensions 0.025 mm x 0.8 mm x 3 mm, 0.1 m/N compliance and 1.5 kHz resonant frequency. Confocal position sensors focused on each cantilever provide position and force resolution < 1 nm/square root Hz and < 10 nN/square root Hz respectively. The motor structure can produce displacements > 0.1 mm and forces > 0.1 mN. A custom Visual Basic.Net software interface to a National Instruments data acquisition card implements real time digital control over 4 input channels and 2 output channels at 20 kHz. In addition, algorithms for both swept sine and stochastic system identification have been written to probe mechanical systems. The device has been used to find the dynamic stiffness of a 5 microm diameter polymer fiber between 0 and 500 Hz. PMID- 17272115 TI - Development of an MR-compatible optical force sensor. AB - This paper presents the principle, structure and performance of a newly developed MR-compatible force sensor. It employs a new optical micrometry that enables highly accurate and highly sensitive displacement measurement. The sensor accuracy is better than 1.0 %, and the maximum displacement of the detector is about 10 microm for a range of the applied force from 0 to 6 N. PMID- 17272116 TI - A new method for measuring the ballistocardiogram using EMFi sensors in a normal chair. AB - Ballistocardiography is a non-invasive technique for the assessment of cardiac function. We built a measurement setup to measure the ballistocardiogram from a normal chair using EMFi sensors. The ballistocardiogram is recorded from a subject sitting on the chair. The measured signal is amplified by a specially designed charge amplifier and digitized by a circulation monitor. A PC provides a user interface for the measurement devices, records the data and displays the results. Impedance cardiography and ECG serve as reference measurements for the ballistocardiography. To test the system, one healthy 24-year-old male and one healthy 22-year-old female were measured. It is concluded that the ballistocardiogram waveforms described in the literature can be recognized from the EMFi signal measured from a normal chair. PMID- 17272117 TI - A sensitive flow-through microcalorimeter for measuring the heat production of cardiac trabeculae. AB - Measurement of the energy consumption of isolated cardiac muscle requires a flow through microcalorimeter with sensitivity in the microW range. In this paper we describe and characterize a sensitive flow-through microcalorimeter, designed and constructed for measuring the heat output of cardiac trabeculae. The device exploits a non-contact, temperature-sensing technique utilizing infra-red sensitive, thin-film thermopile sensors. The microcalorimeter achieves a sensitivity of 1.8-1.9 V/W at a flow rate of 1 microl/s, with a time constant of approximately 3.5 s. The typical power signal-to-noise ratio is better than 200. Predictions of a finite element model of the calorimeter's characteristics compare favourably with measured data. PMID- 17272118 TI - Van der Waals and ideal gas models for compressibility by means of pressure in pneumatic pipes from 1 to 100 Lpm. AB - The general aim is to develop a Venturi flow sensor for the inspiration line to be used in mechanical ventilation. This work is an advance for the development and construction of this sensor and to explain some of its characteristics in mechanical ventilation. The Mach number in this sensor grows with the pipe diameter, but it is less than 0.3 to diameters higher than 3mm, and according to the traditional bibliography it can be used as incompressible fluid for the design. For this reason the simulations were done between 2:1 and 6:1 to simulation pressures from 15 to 16.5 Psi (mechanical ventilation range). The results of these simulations are: it needs to consider the gas compressibility levels for Mach numbers smaller than 0.3 because the error of flow measure can be between 5 and 15% for the pattern of ideal gas and enter 7.5 to 20% for the Van Der Waals model above the incompressibility pattern, and these results were used for the construction of the small reduction the Venturi's pipe from 3 to 78 Lpm, taken from absolute pressure to complete the norm ISO9360. PMID- 17272119 TI - Micro-channel flow analyzers for visualization of micro-fluidic simulations. AB - Micro-channel flow analyzers (MC FANs) are a series of instruments that have been developed for studying blood flow as a measurement of health. The micro-machined silicon chip whose channel size is similar to the human capillary is utilized in these instruments to simulate blood flow. The current versions of instruments are single purposed and intended to make the measurements easy and consistent for studying blood flow only. However, potential applications are easily envisioned for future upgrades. Some examples of potential uses of such instruments are discussed. PMID- 17272120 TI - A hydrogel-actuated microvalve for smart flow control. AB - We report on the fabrication and testing of a hydrogel-actuated smart microvalve for biomedical applications. The three-layered microvalve is composed of a stimuli-sensitive "intelligent" hydrogel sandwiched between a porous silicon membrane and a bossed PDMS flexible diaphragm. The entrapped hydrogel in response to changes in the external physiological stimuli (e.g., pH, glucose, etc.), which diffuses through the porous membrane, swell and deswell hence deflecting the flexible PDMS diaphragm and controlling the closure and opening of the microvalve inlet. A microvalve incorporating a 155 microm thick hydrogel (poly(methacrylic acid-co-acrylamide), mAA-co-AAm) has a response time of 3.6 min to a sudden pH change (pH=3 to pH=7). PMID- 17272121 TI - An imaging system of incipient slip for modelling how human perceives slip of a fingertip. AB - This paper presents the structure and performance of the newly developed fingerprint imaging system, and the outline of the image processing for the quantification of incipient slip. Incipient slip, that is considered to have direct relation with slip perception, is visualized as distortion of a fingerprint pattern. A force sensor for the contact force measurements are also newly developed. Thus this system enables highly accurate incipient slip and fingertip contact force measurements. PMID- 17272122 TI - Measurements of heart motion using accelerometers. AB - We have used acceleration sensors to monitor the heart motion during surgery. A three-axis accelerometer was made from two commercially available two-axis sensors, and was used to measure the heart motion in anesthetized pigs. The heart moves due to both respiration and heart beating. The heart beating was isolated from respiration by high-pass filtering at 1.0 Hz, and heart wall velocity and position were calculated by numerically integrating the filtered acceleration traces. The resulting curves reproduced the heart motion in great detail, noise was hardly visible. Events that occurred during the measurements, e.g. arrhythmias and fibrillation, were recognized in the curves, and confirmed by comparison with synchronously recorded ECG data. We conclude that acceleration sensors are able to measure heart motion with good resolution, and that such measurements can reveal patterns that may be an indication of heart circulation failure. PMID- 17272123 TI - In vivo noninvasive monitoring of cerebral blood with optoacoustic technique. AB - We present the results of blood oxygenation (oxyhemoglobin saturation) measurements using an optoacoustic system in vivo in the superior sagittal sinus of sheep. The system included a nanosecond Nd:YAG laser as a source of radiation and a specially designed optoacoustic probe for signal detection. The optoacoustic signal induced in the superior sagittal sinus by the nanosecond laser pulses correlated well with actual oxyhemoglobin saturation measured with CO-oximeter. We propose to use a two- or multi- wavelength optoacoustic system for noninvasive continuous monitoring of cerebral venous blood oxygenation. The spectra of effective attenuation coefficient were measured in the range 680-1300 nm for oxy- and deoxygenated whole blood and can be employed for calibration of the system. PMID- 17272124 TI - Development of noninvasive tonometer using resonance phenomenon. AB - A tonometer is used to measure ocular pressure either by shooting a short blast of compressed air onto the cornea or by applying pressure directly to the cornea. At present, the tonometer is the primary instrument available for measuring ocular pressure. However, measuring ocular pressure by such means can either frighten or injure the patient. We propose an improved method of measuring ocular pressure in which the tonometer is applied over the patient's closed eyelid for several seconds. The sensor part of the newly developed tonometer contains a bimorph type transducer and weighs only 28.7 (g). When the sensor is placed on the eyelid and the transducer is vibrated by altering the applied voltage, the current flowing through the transducer changes in relation to the ocular pressure. Ocular pressure can thus be determined based on the current flowing through the system. During measurement, patients are generally unaware of the vibrations of the sensor and report no pain. PMID- 17272125 TI - Optoacoustic technique for continuous, noninvasive measurement of total hemoglobin concentration: an in vivo study. AB - We used an optoacoustic technique to measure continuously and noninvasively total hemoglobin concentration in human blood in vivo. An optoacoustic probe, which combined illuminating fibers and a piezoelectric sensitive element, was placed in contact with the skin over the radial artery. Measurements in healthy volunteers agreed well with actual hemoglobin concentration. PMID- 17272126 TI - Beam shape, focus index, and localization error for performance evaluation of a multisensor stethoscope beamformer. AB - This paper proposes methods for evaluating a multisensor system consisting of several stethoscope chest pieces simultaneously recording and storing audio data for computer-aided analysis. To illustrate this concept, we use a circular array of microphones in a free-field homogeneous medium and use delay-and-sum beamforming to combine the received signals. The evaluation methods shown here are applicable to any other non-homogeneous medium and beamforming technique. Beam shape, focus index, and localization error are the methods of performance evaluation discussed in this paper. Several beam shapes are shown and described. The proposed "focus index", a new performance metric, compares the power of signals received from different areas within the array and comes up with a numerical indicator of the focus achieved by the beamformer. This paper also describes a method for localizing a sound source in the near-field of a microphone array by comparing the delay between signals received at known microphone locations. Simulation as well as verification results are presented. PMID- 17272128 TI - Evaluation of impedance spectroscopy for the characterization of small biological samples in tissue-based test systems. AB - Marker free techniques are needed for the construction of efficient tissue-based test and sensor systems. In principle biological tissue can be characterized by impedance spectroscopy. In this paper we investigate by simulation how sensitive parameters of small biological tissue samples can be determined by impedance spectroscopy under optimal measurement conditions. Further, we experimentally evaluate whether the effects of different clinical relevant radio therapy variants on 3D in vitro tumor models are determinable and distinguishable by impedance spectroscopy using a tissue-based test system. The simulations demonstrate that changes in tissue parameters related to the extracellular space are determinable with a high sensitivity. The experiments show that the effect of different radiation dose levels on 3D in vitro tumor models can be determined and distinguished by using a capillary measurement system and impedance spectroscopy. These results are relevant for the development of tissue-based test and sensor systems using impedance spectroscopy to evaluate personalized therapy variants or new therapy approaches. PMID- 17272127 TI - Neural recording chip with penetrating Si microprobe electrode array by selective vapor-liquid-solid growth method. AB - This paper reports on the development of neural recording chip device with penetrating Si microprobe electrode array using IC-process. The Si microprobe electrode array each with a few microns in diameter was grown at predetermined positions with interconnection-wirings. Controlling the diameter and the length of Si probes can be realized by a selective vapor-liquid-solid (VLS) growth. In this work, Si probes with 2 mum in diameter and 60 microm in length were fabricated, which were conductive-Si probes and they were encapsulated with SiO2 layers. To reduce the impedance of Si probes, the tips of Si probes were coated with a metal Au layer. As a result, penetrating Si microprobes measured in saline solution, showed impedance of the order of 300 k to 500 komega at 1 kHz. Packaging techniques for the probe chip were performed with a fluid-tight chamber and a flexible-printed-circuit of polyimide for neural recording experiments. PMID- 17272129 TI - New concepts for chip-supported multi-well-plates: realization of a 24-well-plate with integrated impedance-sensors for functional cellular screening applications and automated microscope aided cell-based assays. AB - Based on the experience with multiparametric bioelectronic sensor chips for the monitoring of living cells, we have combined the established multi-well-format with the advantages of microelectronic sensors. The result is a 24-well-plate where the bottom of the wells is replaced by glass-based chips with integrated IDES (interdigital electrode structure). By using IDES it is possible to detect adhesion and morphological changes of adherent growing cell cultures. Up to now these measurements were inaccessible in conjunction with multi-well-plates, especially in high throughput applications. If microscopic monitoring of the cell culture is required, the IDES can be fabricated using transparent conductor materials like ITO (indium tin oxide). Both the transparent material for the sensors and the sensor-carrier make the multi-well-plate also applicable for all kinds of fluorescence and luminescence biological tests. In addition to the impedance-sensors optical read-out sensor layers for pH and pO2 can be integrated. For this reason there are many possible fields of application in biological and biomedical areas such as drug screening, chemosensitive testing and environmental toxicology as well as in biosensing for biological and chemical warfare. Especially the possibility of using this multi-well-plate together with automated imaging-systems has the great advantage of combining optical and sensory monitoring accessible to high-throughput-applications. PMID- 17272130 TI - A bone-material-based sensor. AB - Bones are now considered as a well accepted series of piezoelectric materials. Several researchers have used the bone material to develop piezoelectric sensors for the measurement of pressure, force, acceleration and other such parameters. However, with the advancement of technology in sensor systems, micro and nanoscale devices are now being developed by using semiconductor or biological materials, all over the world. Bio-chips based on DNA, and bio-MEMS, etc are some of the examples. In the present research, new bone chips have been developed for various sensor applications, mainly micro or nanoscale systems. Design and fabrication aspects of the bone sensor chips for nanotransducers are discussed in detail here. Possible biomedical applications of these chips are also given in brief. PMID- 17272131 TI - Greater than 10(6) optical isolation in integrated optoelectronic fluorescence sensor. AB - Integrated optoelectronic sensors hold much potential for bio-medical applications. Our work focuses on the use of semiconductor lasers, photodetectors and filters to create a monolithically integrated near-infrared fluorescence sensor. Previous research has found that the close integration of these components results in large laser background levels from spontaneous emission emitted from the side of the laser and limits sensor sensitivity. This work presents an improved optical blocking structure between the laser and photodetector which results in greater than 10(6) optical isolation. This level of isolation will allow for sensitive fluorescence detection and shows that optoelectronic components can be successfully integrated for such purposes. PMID- 17272132 TI - Senciltrade mark project: development of a percutaneous optical biosensor. AB - We describe the design, fabrication method, biocompatibility test results, and first application of the novel chemical sensor technology that is under development. The sensor is designed to be minimally invasive, disposable and easily readable to make frequent measurements of various analytes in vivo over a period of 1-3 months. It uses photonic sensing of a chemical reaction that occurs in a polymer matrix bound to the internal end of a chronically implanted percutaneous optical fiber. PMID- 17272133 TI - SLAP: design software for optimization of fluorescence analysis systems. AB - Initial results of a comprehensive design software that optimizes parameters for fluorescence analysis of a user-defined fluorophore are presented. SLAP (spectral LED aggregation program) automatically selects configurations of LEDs that, in a fluorescence analysis system, maximize the emission signal (useful output) as a function of the excitation signal (interference), optics, photodetection modality, and sample characteristics. Initial results draw on an extensive database of blue, blue-green, green and purple LEDs characterized across a range of nominal and overdrive operating conditions. Overdrive conditions enable spectral shifts of the LED excitation bands to enhance the overall flexibility of SLAP optimization. Representative results show a 70.1% improvement in collected signal for GFPuv fluorophores when compared to conventional LED-based fluorescence operated under nominal operating conditions. PMID- 17272134 TI - Enhanced fluorescence emission using a programmable, reconfigurable LED-array based light source. AB - An array of up to 5 LEDs is presented to optimize the excitation signal that is transferred into a fluorescence analysis system. The array is varied by both type and drive current in order to broadly and narrowly tune the aggregate spectrum generated by the LED array to more closely match the desired excitation spectrum. Optimization results are shown for (a) a theoretical desired spectrum that clearly shows the increased flexibility of the LED array; (b) an experiment with AM1 bacteria demonstrating comparable emission output between a conventional Xenon lamp and an over driven LED array; and (c) an experiment with Rhodamine G that shows over a two-fold improvement in signal to noise ratio (or emission) obtainable using an optimized array over a non-optimized array. The flexibility of the LED array offers up to 3.2 million possibilities for aggregate spectra; without overdrive conditions, the 5-element array can only be configured into a maximum of 1020 different aggregate spectra. PMID- 17272135 TI - Initial development of an integrated optoelectronic probe for biomedical imaging. AB - There has recently been increased interest and progress in the development of medical diagnostic techniques based on the optical properties of tissues (e.g. optical absorption and scattering at different wavelengths) and various substances of interest (e.g. fluorescence of intra-cellular structures, drugs, or dyes). Many applications could be envisaged for an optical probe or imaging system that is both inexpensive and small enough to be portable or even implantable. However, current systems do not meet these two criteria, as they are generally constructed using discrete components. We present an integrated circuit implementation of an optical probe, where a detector and receiver circuit are fabricated together on a single chip in a standard analog CMOS process. The advantages of an integrated probe, as opposed to a more conventional optical fiber-based approach, include improvements in light collection efficiency, signal to noise ratio, size, and cost. PMID- 17272136 TI - Development of a FRET based fiber-optic biosensor for early detection of myocardial infarction. AB - A novel optical biosensor technique is being investigated for early detection of myocardial infarction utilizing the distance-dependent chemical transduction method of fluorescence resonance energy transfer (FRET). The FRET process requires two fluorophores termed the donor and the acceptor. When in close proximity, the donor absorbs energy from the excitation source and nonradiatively transfers the energy to the acceptor, which in turn emits fluorescent energy. This distance dependent property was utilized to detect conformational changes when antibodies combine with their respective antigens. The fluorophores were conjugated to an antibody-protein A complex and then immobilized to the distal end of an optical fiber. FRET-induced changes in fluorescence were measured as the maximum areas under the donor and acceptor fluorophore emission spectrum, P1 and P2 respectively. Results showed that the addition of specific HuIgG antigen reduced the P1/P2 ratio in five of the six fibers tested. A reduction in the P1/P2 ratio indicated that the antibodies underwent a conformational change upon binding, reducing the distance between the FRET fluorophores. More experiments need to be performed to further characterize the effects of the fiber preparation, immobilization procedure, instrumental sensitivity, and fluorophores concentration on the function and calibration of FRET-based biosensors. PMID- 17272137 TI - Development of a system for simultaneous 31P NMR and optical transmembrane potential measurement in rabbit hearts. AB - The aim of this study is to develop a system for the first simultaneous measurements using 31P NMR and optical transmembrane potential-sensitive fluorescence. 31P NMR is used to evaluate 5 metabolic markers (pH, sugar phosphates, phosphocreatine, phospholipid intermediates and ATP). Action potential duration is measured with a transmembrane potential-sensitive fluorescent dye, di-4ANEPPS. The system is intended to correlate the action potentials with the metabolic markers and their changes during the time course of cardiac ischemia. The requirements of this system include fabrication of a NMR probe large enough for rabbit heart experiments, incorporation of light guides for excitation of dye and collection of fluorescence in hearts located within a NMR magnet and with minimal disturbance of the magnetic field. The quality factor (Q) of the probe's coil was measured. Control NMR spectra were then acquired with phosphorus test solution. Further spectra were obtained after addition of the optical elements. Results show the ability to use our new probe to acquire a spectrum in the presence of the optical elements within the magnet, suggesting the possibility that 31P NMR spectroscopy and optical transmembrane potential measurements can be performed simultaneously in hearts. PMID- 17272138 TI - Optimal design of nanoengineered implantable optical sensors using a genetic algorithm. AB - A genetic algorithm as a design tool for optimized optical glucose sensors is presented. These proposed sensors are fabricated by assembling ultrathin polyelectrolyte films on the surface of calcium alginate microspheres containing glucose oxidase and an oxygen-quenched ruthenium fluorophore. The sensors are rendered ratiometric by inclusion of a complementary reference fluorophore via polyelectrolyte-dye conjugates. The genetic algorithm, in conjunction with a computational model of the chemical sensor, selects the optimal values for diffusivities of glucose and oxygen in the polyelectrolyte films, the enzyme concentration, microsphere radius, and film thickness that give the optimum sensor response. The values given by the genetic algorithm will be used to design future sensor prototypes. PMID- 17272139 TI - An on-chip programmable instrumentation microsystem for gastrointestinal telemetry applications. AB - We have developed an integrated circuit microsystem instrument using a design methodology akin to that for system-on-chip microelectronics. The microsystem is optimised for low-power gastrointestinal telemetry applications and includes mixed-signal sensor circuits, programmable digital system, a feedback clock control loop and RF circuits that were integrated on a 5 mm x 5 mm silicon chip using a 0.6 microm, 3 V CMOS process. Unintended signal coupling between circuit components has been investigated and current injection into sensitive instrumentation nodes has been minimised. Tests show that the wireless instrument on-chip worked as intended. PMID- 17272140 TI - Performance of a radio link between a base station and a medical implant utilising the MICS standard. AB - Modern medical implants are of increasing complexity and with that, the need for fast and flexible communication with them grows. A wireless system is preferable and an inductive link is the most commonly used. But it has the drawback of a very short range, essentially limited to having the external transceiver touching the patient. The Medical Implant Communication System, MICS, is a standard aimed at improving the communication distance. It operates at a higher frequency band between 402 MHz and 405 MHz. We have by simulations and measurements investigated the channel properties of this band and calculated the link performance for a typical implant application. The result is a link speed between a base station and a bedridden patient of 600 kbit bits per second with a bit error rate of 2% in the downlink to the implant and 1 % in the uplink to the base station. Conclusions on the necessary complexity of the base station are also given. PMID- 17272141 TI - A low-power FM transmitter for use in neural recording applications. AB - We present a low power FM transmitter for use in neural recording telemetry. The transmitter consists of a low noise biopotential amplifier and a voltage controlled oscillator used to transmit the amplified neural signals at a frequency of 433 MHz. The circuit is powered through a transcutaneous, inductive link. The power consumption of the transmitter is measured to be 465 microW. Using a 1/8-wavelength monopole antenna, a received power level was measured to be -54.5 dBm at a distance of one meter. PMID- 17272142 TI - A wireless device for measuring hand-applied forces. AB - We report on a wireless, electromyography (EMG)-based, force-measuring system developed to quantify hand-applied loads without interfering with grasping function. A portable surface EMG device detects and converts to voltage output biopotentials generated by muscle contractions in the forearm and upper arm during hand-gripping and traction activities. After amplifying and bandpass filtering, our radio frequency (RF)-based design operating at approximately 916 MHz wirelessly transmits those voltages to a data acquisition (DAQ) system up to 20 meters away. A separate calibration system is used to relate an individual user's EMG signal to known pull and clenching forces during specific applications. Real-time EMG data is processed and displayed in software developed with LabView (National Instruments, Austin, TX). Data is then converted to force data using individual calibration curves. With EMG electrodes placed over any major forearm muscle, calibration curves for seven subjects demonstrated linearity (R(2) > 0.9) and repeatability (<10% of average slope) to 110 newtons (N). Preliminary results in clinical application on newborn delivery suggest that this approach may be effective in providing an unobtrusive and accurate method of measuring hand-applied forces in applications such as rehabilitation and training. PMID- 17272143 TI - An autonomous control and monitoring system for lower limb orthosis: the gait project case. AB - A wearable control and monitoring system has been developed for a novel active orthotic device. The development addresses the need of an autonomous tool for gait analysis during normal use of the orthotic device. The system has two basic components: the base unit and the ambulatory Uniu. The units communicate by means of a Bluetooth link. In order to test the system, a knee-ankle-foot orthosis has been instrumented for gait control and monitoring of biomechanical and comfort data during daily use by patients with muscular deficiencies. This paper describes the system developed, outlines its performance and presents measurements recorded while performing different activities. PMID- 17272144 TI - A low power medium access control protocol for wireless medical sensor networks. AB - The concept of a wireless integrated network of sensors, already applied in several sectors of our everyday life, such as security, transportation and environment monitoring, can as well provide an advanced monitor and control resource for healthcare services. By networking medical sensors wirelessly, attaching them in patient's body, we create the appropriate infrastructure for continuous and real-time monitoring of patient without discomforting him. This infrastructure can improve healthcare by providing the means for flexible acquisition of vital signs, while at the same time it provides more convenience to the patient. Given the type of wireless network, traditional medium access control (MAC) protocols cannot take advantage of the application specific requirements and information characteristics occurring in medical sensor networks, such as the demand for low power consumption and the rather limited and asymmetric data traffic. In this paper, we present the architecture of a low power MAC protocol, designated to support wireless networks of medical sensors. This protocol aims to improve energy efficiency by exploiting the inherent application features and requirements. It is oriented towards the avoidance of main energy wastage sources, such as idle listening, collision and power outspending. PMID- 17272145 TI - Optimization of wireless Bluetooth sensor systems. AB - Within this study, three different Bluetooth sensor systems, replacing cables for transmission of biomedical sensor data, have been designed and evaluated. The three sensor architectures are built on 1-, 2- and 3-chip solutions and depending on the monitoring situation and signal character, different solutions are optimal. Essential parameters for all systems have been low physical weight and small size, resistance to interference and interoperability with other technologies as global- or local networks, PC's and mobile phones. Two different biomedical input signals, ECG and PPG (photoplethysmography), have been used to evaluate the three solutions. The study shows that it is possibly to continuously transmit an analogue signal. At low sampling rates and slowly varying parameters, as monitoring the heart rate with PPG, the 1-chip solution is the most suitable, offering low power consumption and thus a longer battery lifetime or a smaller battery, minimizing the weight of the sensor system. On the other hand, when a higher sampling rate is required, as an ECG, the 3-chip architecture, with a FPGA or micro-controller, offers the best solution and performance. Our conclusion is that Bluetooth might be useful in replacing cables of medical monitoring systems. PMID- 17272146 TI - Development of a small wireless position sensor for medical capsule devices. AB - Medical capsule devices such as video capsule endoscopes are finding increasing use in clinical applications. At present, technologies capable of measuring capsule position in the digestive tract have not yet been established. The present study aims to develop a small wireless position sensor capable of measuring capsule position based on the phenomenon of mutual induction. Currents into primary coils are adjusted to maintain electromotive force induced in secondary coils at a constant level. Electromotive forces induced in the secondary coils are modulated to FM signals using an astable multivibrator, and the signals are passed directly through living tissue at low current and then demodulated by detectors on the surface of the body. A prototype wireless sensor was developed and evaluated in vitro. The sensor was capable of accurately measuring capsule position up to 500 (mm) from the primary coils with an accuracy of 5 (mm). Miniaturization of the sensor is necessary for commercialization. PMID- 17272147 TI - A portable, low-power, wireless two-lead EKG system. AB - Sensor devices ("motes") which integrate an embedded microprocessor, low-power radio and a limited amount of storage have the potential to significantly enhance the provision of emergency medical care. Wearable vital sign sensors can wirelessly monitor patient condition, alerting healthcare providers to changes in status while simultaneously delivering data to a backend archival system for longer-term storage. As part of the CodeBlue initiative at Harvard University, we previously developed a mote-based pulse oximetry module which gathers data from a noninvasive finger sensor and transmits it wirelessly to a base station. To expand the capabilities of the mote for healthcare applications we now introduce EKG on Mica2, the first custom-designed electrocardiograph sensor board to interface with this platform. We additionally present VitalEKG, a collection of software components which allow the capture and wireless transmission of heart activity traces. We present preliminary test results which validate our approach and suggest the feasibility of future enhancements. PMID- 17272148 TI - A fiber-optic powered wireless sensor module made on elastomeric substrate for wearable sensors. AB - We demonstrate an integrated sensor module that combines a photonic nano-porous sensor and a bias-free optical powered RF transducer. The sensor signal is encoded in the RF frequency ready for transmission. The entire sensor module does not include battery and is constructed with the flexible and biocompatible elastomeric polymer, PDMS. This technology holds promise for wearable sensors. PMID- 17272149 TI - A critical appraisal of opportunities for wearable medical sensors. AB - This paper provides an appraisal of the sensor requirements and prospects available for the growing field of wearable medical sensors. The results of a literature survey for various sensor use-models indicate that the design goals for each intended sensor application must focus on task specific criteria for ultimate sensor acceptance. Provided use-models include the examination of the relevant medical problems, the diagnostic utility of the available physiologic signals, and the impact of false alarms on the specific implementation area. PMID- 17272150 TI - A novel algorithm to separate motion artifacts from photoplethysmographic signals obtained with a reflectance pulse oximeter. AB - Pulse oximeters are mainstays for acquiring blood oxygen saturation in static environments such as hospital rooms. However, motion artifacts prevent their broad in wearable, ambulatory environments. To this end, we present a novel algorithm to separate the motion artifacts from plethysmographic data gathered by pulse oximeters. This algorithm, based on the Beer-Lambert law, requires photoplethysmographic data acquired at three excitation wavelengths. The algorithm can calculate venous blood oxygen saturation (SvO2) as well as arterial blood oxygen saturation (SaO2). Preliminary results indicate that the extraction of the venous signal, which is assumed to be most affected by motions, is successful with data acquired from a reflectance-mode sensor. PMID- 17272151 TI - Active noise cancellation using MEMS accelerometers for motion-tolerant wearable bio-sensors. AB - An active noise cancellation method using a MEMS accelerometer is developed for recovering corrupted wearable sensor signals due to body motion. The method is developed for a finger ring PPG sensor, the signal of which is susceptive to the hand motion of the wearer. A MEMS accelerometer (ACC) imbedded in the PPG sensor detects the hand acceleration, and is used for recovering the corrupted PPG signal. The correlation between the acceleration and the distorted PPG signal is analyzed, and a low-order FIR model relating the signal distortion to the hand acceleration is obtained. The model parameters are identified in real time with a recursive least square method. Experiments show that the active noise cancellation method can recover ring PPG sensor signals corrupted with 2G of acceleration in the longitudinal direction of the digital artery. PMID- 17272152 TI - Wrist ambulatory monitoring system and smart glove for real time emotional, sensorial and physiological analysis. AB - Improvement of the quality and efficiency of the quality of health in medicine, at home and in hospital becomes more and more important Designed to be user friendly, smart clothes and gloves fit well for such a citizen use and health monitoring. Analysis of the autonomic nervous system using non-invasive sensors provides information for the emotional, sensorial, cognitive and physiological analysis. MARSIAN (modular autonomous recorder system for the measurement of autonomic nervous system) is a wrist ambulatory monitoring and recording system with a smart glove with sensors for the detection of the activity of the autonomic nervous system. It is composed of a "smart tee shirt", a "smart glove", a wrist device and PC which records data. The smart glove is one of the key point of MARSIAN. Complex movements, complex geometry, sensation make smart glove designing a challenge. MARSIAN has a large field of applications and researches (vigilance, behaviour, sensorial analysis, thermal environment for human, cognition science, sport, etc...) in various fields like neurophysiology, affective computing and health monitoring. PMID- 17272153 TI - Knitted bioclothes for health monitoring. AB - An innovative system named WEALTHY is presented, where conducting and piezoresistive yarns are integrated in a knitted garment and used as sensor and electrode elements. The system allows the simultaneous recording of vital signs as well as parameters' extrapolation and inter-signal elaboration that contribute to produce alert messages and synoptic patient table. The system aims to assist cardiac patients during rehabilitation phase, patients can be continuously followed during selected time intervals, such as during physical activity or occurrence of symptoms, to discover potential threats, to tailor the best medical treatment for long term care, and to generate appropriate alerts to patient, physician or emergency medical systems. The system can also assist professional workers subject to considerable physical and psychological stress and/or environmental and professional health risks. Finally, by providing direct feedback to the users, WEALTHY can act on the level of awareness and allow better control of their own condition. PMID- 17272154 TI - A PDA-based electrocardiogram/blood pressure telemonitor for telemedicine. AB - An electrocardiogram (ECG) / blood pressure (BP) telemonitor consisting of comprehensive integration of various electrical engineering concepts, devices, and methods was developed. This personal digital assistant-based (PDAbased) system focused on integration of biopotential amplifiers, photoplethysmographic measurement of blood pressure, microcontroller devices, programming methods, wireless transmission, signal filtering and analysis, interfacing, and long term memory devices (24 hours) to develop a state-of-the-art ECG/BP telemonitor. These instrumentation modules were developed and tested to realize a complete and compact system that could be deployed to assist in telemedicine applications and heart rate variability studies. The specific objective of this device was to facilitate the long term monitoring and recording of ECG and blood pressure signals. This device was able to acquire ECG/BP waveforms, transmit them wirelessly to a PDA, save them onto a compact flash memory, and display them on the LCD screen of the PDA. It was also capable of calculating the heart rate (HR) in beats per minute, and providing systolic and diastolic blood pressure values. PMID- 17272155 TI - A hydrostatic pressure approach to cuffless blood pressure monitoring. AB - This paper presents the underlying principle and accompanying initial validation results towards the development of an optically-based, cuffless blood pressure monitoring method. As opposed to traditional oscillometric techniques, the optical sensor is calibrated with a known patient-controlled hydrostatic perturbation. In particular, the hydrostatic pressure challenge is utilized to parameterize the characteristic sigmoidal vascular compliance curve that links transmural pressure to the measured PPG output. Formulation of the compliance model will be accompanied by experimental results demonstrating the utility of the method. PMID- 17272156 TI - Wearable wireless biopotential measurement device. AB - A light wearable wireless biopotential measurement device built up of commercial components is presented. The device utilizes 868 MHz ISM license free frequency band. Very low noise and good interference rejection is achieved using three electrode differential amplifier design and wireless signal transfer. The device has a possibility of calculating heart rate when ECG signal is measured, and transmitting only the heart rate value while conserving power. PMID- 17272157 TI - Preliminary evaluation of a full-time falling monitor for the elderly. AB - The article presents the early outcomes of the evaluation of an intelligent accelerometer unit (IAU) utilized for detecting the falling events of elderly people . The overall design of the monitor where the IAU is integrated is briefly exposed. The outcomes of a laboratory study carried out over 8 volunteers show that the device is able to distinguish true falling events from normal activities like fast walking or going up/downstairs. The influences of the subject and the environment have been taken into account profiting from the processing capacity of the monitor distributed architecture. PMID- 17272158 TI - Wearable approach for continuous ECG--and activity patient-monitoring. AB - The paper describes an approach to monitor a person's ECG and activity continuously with functional clothing. A belt with integrated electronics has been developed and has proven long-term robustness of all electrical components. A low-power module measures the ECG signal as well as the acceleration (2-axis) and stores data continuously up to two days. A user test has been performed to evaluate the belt according to system performance at different daily-life activities like sleeping, walking and so on. System parameters are ECG-signal quality, system up-time, and ECG-signal coverage during a day. PMID- 17272159 TI - Evaluations of the ring shaped EMG measurement system. AB - This paper describes two evaluations of our previously proposed ring shaped EMG measurement system. The first evaluation, based on the collection of EMG by the system, shows that no statistically significant difference is seen between 3 EMG electrode configurations: the electrode is pressed with a finger, the electrode is fixed by tape, and a conventional plate electrode. The second evaluation suggests that our system has higher usability than the conventional electrodes. These results show that the ring shaped EMG measurement system is effective for measuring EMG, especially as part of the user interface for EMG-based applications. PMID- 17272160 TI - Lifeguard--a personal physiological monitor for extreme environments. AB - Monitoring vital signs in applications that require the subject to be mobile requires small, lightweight, and robust sensors and electronics. A body-worn system should be unobtrusive, noninvasive, and easy-to-use. It must be able to log vital signs data for several hours as well as transmit it on demand in real time using secure wireless technologies. The NASA Ames Research Center (Astrobionics) and Stanford University (National Center for Space Biological Technologies) are currently developing a wearable physiological monitoring system for astronauts, called LifeGuard, that meets all of the above requirements and is also applicable to clinical, home-health monitoring, first responder and military applications. PMID- 17272161 TI - A Web-based vital sign telemonitor and recorder for telemedicine applications. AB - We describe a vital sign telemonitor (VST) that acquires, records, displays, and provides readings such as: electrocardiograms (ECGs), temperature (T), and oxygen saturation (SaO2) over the Internet to any site. The design of this system consisted of three parts: sensors, analog signal processing circuits, and a user friendly graphical user interface (GUI). The first part involved selection of appropriate sensors. For ECG, disposable Ag/AgCl electrodes; for temperature, LM35 precision temperature sensor; and for SaO2 the Nonin Oximetry Development Kit equipped with a finger clip were selected. The second part consisted of processing the analog signals obtained from these sensors. This was achieved by implementing suitable amplifiers and filters for the vital signs. The final part focused on development of a GUI to display the vital signs in the LabVIEW environment. From these measurements, important values such as heart rate (HR), beat-to-beat (RR) intervals, SaO2 percentages, and T in both degrees Celsius and Fahrenheit were calculated The GUI could be accessed through the Internet in a Web-page facilitating the possibility of real-time patient telemonitoring. The final system was completed and tested on volunteers with satisfactory results. PMID- 17272162 TI - A PDA-based flexible telecommunication system for telemedicine applications. AB - Technology has been used to deliver health care at a distance for many years. Telemedicine is a rapidly growing area and recently there are studies devoted to prehospital care of patients in emergency cases. In this work we have developed a compact, reliable, and low cost PDA-based telecommunication device for telemedicine applications to transmit audio, still images, and vital signs from a remote site to a fixed station such as a clinic or a hospital in real time. This was achieved based on a client-server architecture. A Pocket PC, a miniature camera, and a hands-free microphone were used at the client site and a desktop computer running the Windows XP operating system was used as a server. The server was located at a fixed station. The system was implemented on TCP/IP and HTTP protocol. Field tests have shown that the system can reliably transmit still images, audio, and sample vital signs from a simulated remote site to a fixed station either via a wired or wireless network in real time. The Pocket PC was used at the client site because of its compact size, low cost and processing capabilities. PMID- 17272163 TI - Development of novel algorithm and real-time monitoring ambulatory system using Bluetooth module for fall detection in the elderly. AB - Novel algorithm and real-time ambulatory monitoring system for fall detection in elderly people is described. Our system is comprised of accelerometer, tilt sensor and gyroscope. For real-time monitoring, we used Bluetooth. Accelerometer measures kinetic force, tilt sensor and gyroscope estimates body posture. Also, we suggested algorithm using signals which obtained from the system attached to the chest for fall detection. To evaluate our system and algorithm, we experimented on three people aged over 26 years. The experiment of four cases such as forward fall, backward fall, side fall and sit-stand was repeated ten times and the experiment in daily life activity was performed one time to each subject. These experiments showed that our system and algorithm could distinguish between falling and daily life activity. Moreover, the accuracy of fall detection is 96.7%. Our system is especially adapted for long-time and real-time ambulatory monitoring of elderly people in emergency situation. PMID- 17272164 TI - A wireless ECG system for continuous event recording and communication to a clinical alarm station. AB - Development of new wearable biomedical sensors within a wireless infrastructure opens up possibilities for new telemedical applications leading to significant improvements in continuous monitoring, and thereby to better quality of patient care. In this paper we describe a new concept for a wireless electrocardiogram (ECG) system intended for continuous monitoring of ECG activity especially designed for arrhythmia diagnostic purposes. The patient is wearing an ECG sensor, "a smart electronic electrode", with wireless transmission of ECG signals to a dedicated hand held device (HHD). This device is monitoring the continuously recorded ECG signal, and can detect abnormal ECG activity using an automatic arrhythmia detector. Based on this, the device will transmit alarm conditions to a remote clinical alarm station (CAS). The system will act as a continuous event recorder, which can be used to follow up patients who have survived cardiac arrest, ventricular tachycardia or cardiac syncope but also for diagnostic purposes for patients with diffuse arrhythmia symptoms. This paper describes the principle design requirements for the new wireless ECG sensor and system design for the HHD in order to transfer detected alarms to the CAS. PMID- 17272165 TI - Dry electrodes for monitoring of vital signs in functional textiles. AB - Wearable electronics may become a key element in the future to measure a patient's physiological parameters not only in a clinical environment. This work describes dry electrodes based on conductive rubber, which can be integrated into clothing for monitoring purposes. Characteristic electrical properties like warm up time, skin-electrode impedance and motion artefacts will be discussed. PMID- 17272166 TI - Development of a wrist-worn integrated health monitoring system. AB - In this paper, we report upon the prototype development of a wrist-worn integrated health monitoring device (WIHMD) with a tele-reporting function. The functional objective of the WIHMD is to provide information concerning clinical state, such as vital biosignals and locational information, to experts at a distance. Thereby, the unit provides the facility for rapid and appropriate directions to be given by experts in emergency situations, and enables the user or the supervisor to manage changes in health condition with helpful treatment. PMID- 17272167 TI - Real time blood flow velocity monitoring in the microcirculation. AB - A real-time monitoring system based on the dual slit methodology for the characterization of the red blood cell velocity at the level of microcirculation has been developed. The analog photometric signals are acquired and processed using a hybrid hardware-software system that exploits a A/D conversion and an optimized correlation algorithm on an embedded system. It is implemented exploiting the resources of a general purpose board capable to extract the useful information from the noisy photometric signals, to process them, to show and save the results and, therefore, to make the experiments reproducible. Two different approaches to the crosscorrelation algorithm have been tested and their performances have been compared to each. The system has been tested in in vivo experiments on anaesthetized hamsters. Several microvessels have been observed and the results have been compared to the output of an analog crosscorrelator to verify their coherence. PMID- 17272168 TI - Characterization of a novel heart and respiratory rate sensor. AB - Existing methods of electronic patient monitoring require tethering the patient to the device, which is not well tolerated. This study characterizes the performance of a novel sensor array and digital signal processing (DSP) algorithms that extract heart and respiratory rates. The sensor lies under the sheets on a hospital bed, and when the patient lies down, it detects pressure waves generated by the heart, and by the act of breathing. The algorithms identify these signals of interest, filtering out extraneous signals. Output of the algorithms was compared to output from ECG and transthoracic impedance, taken from the same subject, at the same time. Forty-four adult volunteers were recruited. The results demonstrated an average of mean differences for heart rate of 0.50 beats per minute, with a standard deviation of 0.51. The average of mean differences for respiratory rate was 0.39 with standard deviation of 0.55. These results suggest this noninvasive, non-restrictive method of measuring heart and respiratory rates may be a viable solution to the problem of decreased vigilance of patient condition faced on the in-patient wards. Future studies will characterize performance in ill populations, and examine alarm schemes that are both highly sensitive and specific for the target population. PMID- 17272169 TI - Development of a tissue oxygen consumption measurement method based on near infrared photoplethysmography. AB - A dual-wavelength reflectance optical oximeter sensor in combination with a simple photoplethysmographic technique was developed to measure the local tissue oxygen consumption from the simultaneous measurement of the arterio-venous oxygen saturation (SaO2, SvO2) differences, the physiological Fick principle. The performance of the reflectance oximeter was demonstrated in the theoretical simulation of the three-dimensional photon diffusion theory and the experimental study in the human subjects. As the results, the good agreements between theoretical and experimental studies of the oximeter were observed in the range of 70-100% SaO2 and 70-90% SvO2. The reflectance optical local tissue oxygen consumption measurement sensor would be applicable for various fields especially for the sports medicine, the patients monitoring and the transplanting organs monitoring. PMID- 17272170 TI - Real-time estimation of oxygen concentration in micro-hemo-vessels. AB - In this paper, a real-time measurement system for non-invasive evaluation of oxygen concentration (PO2) at the microcirculation level is developed. The system has been designed by exploiting the phenomenon of fluorescence quenching. The skin of an anaesthetized hamster, injected with porphyrin, is lighted with pulses; the fluorophore reacts with the oxygen in the blood, producing a fluorescence signal, and the value of the fluorescence lifetime is related to the oxygen concentration. This microcirculation-based instrumentation consists of an electro-optical system, a control circuit and signal processing procedure. The system allows the measurement of PO2 in the range of 0-700 (mmHg) with a standard deviation of 4 (mmHg). Several experiments have been performed in order to characterize and test this system. PMID- 17272171 TI - Development of an implantable oximetry-based organ perfusion sensor. AB - A sensor system enabling real-time monitoring of organ perfusion following transplantation is presented. This system uses a three wavelength oximetry-based approach. The instrument is intended for implantation at the organ site during transplantation to provide real-time reporting of the perfusion status of the tissue for 7-10 days following the procedure. Data is transmitted from the sensor to a localized receiver using direct sequence spread spectrum techniques at 916 MHz. In this paper, the sensing method and associated electronics implementation are presented. The present status of system miniaturization is summarized along with plans for future miniaturization efforts. Preliminary sensor data is presented demonstrating the efficacy of the technique. PMID- 17272172 TI - Continuous blood pressure monitoring during exercise using pulse wave transit time measurement. AB - This paper gives an overview of a research, which is focused on the development of the convenient device for continuous non-invasive monitoring of arterial blood pressure. The blood pressure estimation method is based on a presumption that there is a singular relationship between the pulse wave propagation time in arterial system and blood pressure. The parameter used in this study is pulse wave transit time (PWTT). The measurement of PWTT involves the registration of two time markers, one of which is based on ECG R peak detection and another on the detection of pulse wave in peripheral arteries. The reliability of beat to beat systolic blood pressure calculation during physical exercise was the main focus for the current paper. Sixty-one subjects (healthy and hypertensive) were studied with the bicycle exercise test. As a result of current study it is shown that with the correct personal calibration it is possible to estimate the beat to beat systolic arterial blood pressure during the exercise with comparable accuracy to conventional noninvasive methods. PMID- 17272173 TI - Computer simulation and tank experimental verification of concentric ring electrodes. AB - Brain activity generates electrical potentials that are spatio-temporal in nature. EEG is the least costly and most widely used non-invasive technique for diagnosing many problems related to the brain. It has very good temporal resolution, but does not poses high spatial resolution primarily due to the blurring affects of the volume conductor. The surface Laplacian enhances the spatial resolution and selectivity of the surface electrical activity as it takes the second spatial derivative of the potential. In an attempt to increase the localization and spatial selectivity a five point finite difference method has recently been used in a bipolar electrode configuration. Here we report on a nine point finite difference method as a model for the tripolar electrode configuration. We have designed a computer simulation to model electrode properties and a dipole at various depths below the electrode surface. A tank experimental was setup to verify the computer simulated potentials. In the simulation and tank experiment, a concentric ring electrode of 2 cm diameter was used. We found that the tripolar electrode configuration has significantly better localization and signal to noise ratio than the bipolar and quasi-bipolar configurations. PMID- 17272174 TI - Reduction of power line interference using active electrodes and a driven-right leg circuit in electroencephalographic recording with a minimum number of electrodes. AB - Unwanted power line interference is one of the most common problems in electroencephalographic recording. This paper examines how the use of active electrodes together with a driven-right-leg circuit can significantly improve interference reduction, even when the same electrode is used for common and reference which is attractive because it saves an electrode. General conclusions about the active electrodes and the driven-right-leg circuits were obtained thanks to a prototype that uses the same electrode for both common and reference. Measurements were performed both on a subject and on an electrical equivalent model. PMID- 17272175 TI - Preamplified two-wired active electrodes with DC-offset compensation. AB - Instrumentation amplifiers are widely used in biosignal measurements, due to their good common mode rejection ratio (CMRR) and their high input impedance. While the fabrication of active electrodes has been reported and their beneficial effects scientifically confirmed their usage in daily practice is still limited. This work describes a new instrumentation amplifier (IA) for biopotentials based on preamplified two-wired active electrodes with a gain of 40 dB. This is possible due to the DC-offset compensation provided by an integrator in the feedback loop. The DC-offset compensation allows for the first time to simultaneously measure the amplified signal and the DC-offset between the inputs. The signal quality is improved by amplifying and buffering the signal on the electrodes. PMID- 17272176 TI - Comparison of bipolar vs. tripolar concentric ring electrode Laplacian estimates. AB - Potentials on the body surface from the heart are of a spatial and temporal function. The 12-lead electrocardiogram (ECG) provides useful global temporal assessment, but it yields limited spatial information due to the smoothing effect caused by the volume conductor. The smoothing complicates identification of multiple simultaneous bioelectrical events. In an attempt to circumvent the smoothing problem, some researchers used a five-point method (FPM) to numerically estimate the analytical solution of the Laplacian with an array of monopolar electrodes. The FPM is generalized to develop a bi-polar concentric ring electrode system. We have developed a new Laplacian ECG sensor, a trielectrode sensor, based on a nine-point method (NPM) numerical approximation of the analytical Laplacian. For a comparison, the NPM, FPM and compact NPM were calculated over a 400 x 400 mesh with 1/400 spacing. Tri and bi-electrode sensors were also simulated and their Laplacian estimates were compared against the analytical Laplacian. We found that tri-electrode sensors have a much-improved accuracy with significantly less relative and maximum errors in estimating the Laplacian operator. Apart from the higher accuracy, our new electrode configuration will allow better localization of the electrical activity of the heart than bi-electrode configurations. PMID- 17272177 TI - Design of surface electrode array for electromyography in the genioglossus muscle. AB - The patency of the upper airway is dependent on the sustained activity of upper airway muscles, in particular the genioglossus (GG) muscles which act to protrude the tongue. Obstructive sleep apnea syndrome (OSAS) is a common and serious disorder in which this mechanism fails, resulting in frequent collapse of the airway during sleep. The properties of the upper airway muscles are therefore of interest in both normal and OSAS subjects, so that their role in the pathogenesis of OSAS can be better understood. Electromyography (EMG) is an important tool for assessing muscle activity and has been used in many GG studies. We have designed a new appliance incorporating a surface electrode array for GG EMG recording. The electrode configuration enables estimation of muscle fibre conduction velocity (CV), an important parameter for monitoring muscle fatigue, which has not been studied before in the GG. The appliance is also designed to provide accurate and repeatable placement of electrodes. Preliminary results presented demonstrate the performance of our appliance, which will now be used to measure GG CV in a range of fatiguing conditions. PMID- 17272178 TI - Modification of pulse wave signals in electrical bioimpedance analyzers for implantable medical devices. AB - The problems of application of pulse wave signals in electrical bioimpedance analyzers foreseen for using in implantable medical devices as diagnostical means are discussed in this paper. The main problem arises at measurement of phasor parameters by the aid of rectangular pulse wave signals. The specific measurement errors appear due to presence of higher harmonics in the spectra of pulse waveforms. These errors are discussed in two cases, in the case of full cycle rectangular waveform, and in the case of using the shortened pulses introduced specially for reduction of errors. PMID- 17272179 TI - Evaluating sleepiness using force platform posturography requires less than 30 seconds of measurement time. AB - We have investigated the relationship between measurement time and accuracy of posturography-based sleep deprivation estimation. Twenty healthy subjects, 20 to 37 years of age, participated in the study. The subjects were deprived of sleep for up to 36 hours. The postural stability of the subjects was measured as a function of sleep deprivation time. The posturographic parameters used for analysing the test data were the fractal dimension of the sway path, the most common frequency of the sway, the time-interval for open-loop control of the stance and the most common amplitude of the sway. Individual case-observations showed that we were able to estimate the sleep deprivation time of individual subjects with an accuracy better than +/-3 hours, when the measurement time was the commonly utilized 30 seconds. Repeating the analysis with shorter measurement times we found that a measurement length of 26, 23, and 20 seconds for the fractal dimension, most common frequency of sway and most common sway amplitude respectively, was required in order to achieve a 20% relative sleep deprivation estimation accuracy. The sleep deprivation estimation accuracy based on the time interval for open-loop control of stance remained at 6% when the measurement time was shortened to 20 seconds. PMID- 17272180 TI - Non-intrusive eye gaze tracking under natural head movements. AB - We propose an eye gaze tracking system under natural head movements. The system consists of one CCD camera and two mirrors. Based on geometric and linear algebra calculations, the mirrors rotate to follow head movements in order to keep the eyes within the view of the camera. Our system allows the subjects head to move 30 cm horizontally and 20 cm vertically, with spatial gaze resolutions about 6 degree and 7 degree, respectively and a frame rate about 10 Hz. We also introduce a hierarchical generalized regression neural networks (H-GRNN) scheme to map eye and mirror parameters to gaze, achieving a gaze estimation accuracy of 92% under head movements. The use of H-GRNN also eliminates the need for personal calibration for new subjects since H-GRNN can generalize. Preliminary experiments show our system is accurate and robust in gaze tracking under large head movements. PMID- 17272182 TI - Contactless measurement strategies and apparatus for mandibular movements monitoring in gnatology. AB - This paper deals with the development of an innovative approach that allows performing non invasive measurements of jaw movements with application to the field of gnatography. An experimental apparatus has been also realized that includes both hardware and software sections. The main characterizing feature of the measurement system proposed here consist in the complete absence of any invasive device with respect to the patient, in fact a stereoscopic artificial vision approach has been exploited to our aims. A large set of experimental verifications of the proposed strategy has been performed and the results obtained confirm the suitability of the approach. PMID- 17272181 TI - Evaluation of postural stability by means of a single inertial sensor. AB - Human posture control during standing is a combination of many complicated control processes. Physical therapists perform different clinical balance tests to either assess postural control or identify balance disorders that can ultimately cause a patient to fall. In this article, several standardized clinical exercises for balance assessment are executed together with an orientation tracker strapped onto the volunteer's sternum. The tracker estimates the 3-D orientation of the trunk in real-time using an efficient attitude determination algorithm. The device is fully portable and sensitive to anteroposterior and mediolateral sways. Analysis of the resulting angles provides several parameters that are useful in assessing and quantifying balance function. This approach could be a valuable tool for a therapist for patient's follow-up and could be combined with existing procedures such as force platforms or optical motion analysis systems. Also, statistical analysis on these parameters could help to characterize normal and pathological performances in a population. PMID- 17272183 TI - A new portable device for ambulatory monitoring of human posture and walking velocity using miniature accelerometers and gyroscope. AB - Measurement of physical activity is one of the key subjects in the field of ambulatory cardiovascular monitoring using such as Holter ECG and so called "ambulatory blood pressure monitor (ABPM)". Rehabilitation and gerontology will also be another fields for the application of the activity monitor. From this point of view, we have developed a portable device for monitoring human posture and walking velocity in ambulatory subjects. In this paper are described, a new sensor system for this purpose using three accelerometers and one gyroscope, its availability for the accurate measurement of human posture and walking velocity, and results of preliminary study using a prototype system for ambulatory monitoring. PMID- 17272184 TI - A wireless measurement system for three-dimensional ocular movement using the magnetic contact lens sensing technique. AB - A new and innovative method to measure the eye movement in a wireless manner was proposed. We verified the feasibility of our idea by fabrication and performance test of a prototype system. The prototype system consisted of a contact lens with a ring-shaped thin magnet, and eyeglasses frame-shaped PCB with analog/digital signal processing circuitry as well as four magnetoresistive sensors. This new method based on the magnetic contact lens sensing technique (MCLST) is expected to overcome all the disadvantages of the existing techniques. PMID- 17272185 TI - Relationship between muscle hardness estimated by the indentation method and muscle contractile level. AB - The purpose of this study was to investigate the relationship between muscle contractile level and hardness by the indentation method. Eleven healthy male subjects were involved in this study. The subjects put their arms horizontally on a table. The subjects were instructed to keep the isometric contractile force constant at three elbow angles. The indentation depth and reaction force of the biceps brachii muscle were measured, and electromyogram (EMG) were done. First, EMGs before and during the indentation were compared. The EMGs showed no significant increase during the indentation. The indentation did not affect muscle activities. Next, the force indentation depth curves were approximated with the non-linear Voigt model by the least square method, and the indices of the elasticity and the viscosity were estimated. Then the relationship between the indices and the contractile levels were investigated. The contractile level was the force normalized by that in the maximum voluntary contraction. The elastic indices increased almost linearly as the contractile levels increased. The relationships at different elbow angles did not show significant differences. However, the characteristics of the viscous indices varied depending on the subjects. PMID- 17272186 TI - Five-band microwave radiometer system for non-invasive measurement of brain temperature in new-born infants: system calibration and its feasibility. AB - Recent simulation studies have shown that a technique of multi-frequency microwave radiometry is feasible for non-invasive measurement of deep brain temperatures in the new-born infants. A five-band microwave radiometer system has been developed, and its operation in a normal electromagnetic environment is checked. Five receivers operating with a waveguide antenna and at center frequencies of 1.2, 1.65, 2.3, 3.0 and 3.6 GHz (0.4 GHz bandwidth) are calibrated using a temperature-controlled water-bath. Temperature resolutions obtained for each receiver are 0.183, 0.273, 0.148, 0.108 and 0.118 K, respectively. A temperature retrieval simulation based on these resolutions and the previously proposed algorithm shows that the confidence interval, as produced by thermal noise, is 0.62 K for the retrieved central brain temperature. If the conductivity of brain is estimated wrong by 10 %, this will result in an error of 0.3-0.4 K. The result of this work is encouraging for realization of radiometric measurement of temperature profile in a baby's head. PMID- 17272187 TI - Images reproducibility of an electrical impedance tomography (EIT) prototype. Analysis of the EIT sensibility in rats in pathological in vivo conditions. AB - The development of a 16 electrode-electrical impedance tomography (EIT) prototype to be applied in neurological fields such as epilepsy in rats has been previously reported. Approaching residual problems in order to improve its performance, this work reports results about changes made in the system hardware as follows: 1) replacing the current source demultiplexing circuit that could impact on a better spatial localization, and 2) a new current source design that increases the current amplitude up to 5 mA/sub rms/. System was evaluated by means of: a) image reproducibility starting from 4 test elements in homogeneous conditions; and b) spatial localization evaluation in conductivity perturbation conditions; this feature is evaluated too in preliminary acute in vivo experiments where an epileptic seizure is induced, and an impedance increase is expected. Results show a 95% of proper images for a) analysis. Spatial localization reports improvement up to 20% transversely and 5.5% longitudinally with regard to previous results. In vivo results are lack of interpretation due poor changes obtained in images. In order to conclude or not a reliable correlation between the perturbation measured and the seizure activity, a new definition of grey scale or other changes could be proposed. PMID- 17272188 TI - Digital phonocardiography: a PDA-based approach. AB - In this paper we demonstrate the applicability of advanced digital signal processing algorithms to the analysis of heart sound signals and describe the development of a PDA-based biomedical instrument capable of acquisition, processing, and analysis of heart sounds. Fourier transform-based spectral analysis of heart sounds was carried out first to show the differences in the frequency contents of normal and abnormal heart sounds. As the time-varying nature of heart sounds calls for better techniques capable of analyzing such signals: the short time Fourier transform (STFT) or spectrogram analysis was performed next. This method performed remarkably well in displaying frequency, magnitude, and time information of the heart sounds, providing robust parameters to make accurate diagnosis. With continuous technological advancements in computing and biomedical instrumentation, and the concurrent popularity of handheld instruments in the medical community, we introduce the concept of PDA based digital phonocardiography. A prototype system is comprised of a digital stethoscope and a pocket PC. Heart sounds are recorded and displayed in the pocket PC screen. Advanced signal processing algorithms are implemented using the combined capabilities of software tools such as LabVlEW and embedded Visual C(++). PMID- 17272189 TI - Experimental study of 3D contactless conductivity detection using microwave radiometry: a possible method for investigation of brain conductivity fluctuations. AB - The capability of detecting electrical conductivity variations using focused microwave radiometry, a method used in clinical applications for temperature distribution imaging of subcutaneous tissues, is discussed in the present study. A novel microwave radiometric system operating at 3.5 GHz, including an ellipsoidal conductive wall cavity, which provides the required beamforming and focusing, is developed. The system is capable of providing distribution measurements of the product of conductivity and temperature of any object being at a temperature above the absolute zero. The implemented experimental procedure is based on the results of an electromagnetic numerical analysis using a semianalytical method which was developed in order to compute the focusing properties of the ellipsoidal reflector. Each measurement is realized by placing the region of interest in the area of the first focus of the cavity and collecting the radiation converged at the second by an almost isotropic dipole antenna connected to a sensitive radiometer. Experimental data from cylindrical shaped saline or de-ionized water filled tank phantoms in which saline solutions of different concentrations were infused, provide promising results concerning the system's ability of detecting conductivity variations. Future research is needed in order to elucidate the potential of the proposed methodology to be used for brain conductivity measurements. PMID- 17272190 TI - Therapy guided by gastric impedance spectroscopy in a septic shock model in pigs. AB - The disruption of the gastric mucosa plays a key role in the evolution of shock and it is the "motor of multiple organ failure"; in this sense, no clinically useful method to directly monitor the level of mucosal ischemic injury is available yet to guide appropriate therapy for the critically ill. An experimental model was developed in order to demonstrate that resuscitation therapy by gastric impedance spectroscopy, using a minimally invasive gastric catheter, is feasible and therefore, to establish its potential as a practical future clinical monitoring tool for the critically ill. A septic shock model in pigs was developed, which reproduces the hemodynamic conditions of the critically ill patient. Intervention therapies were designed in order to promote changes in hemodynamic response as well as in splanchnic perfusion, conventionally guided and by impedance spectroscopy. At the end of experiments, survival in each intervention therapy was compared and the outcome was better in the therapy group guided by gastric electric impedance spectroscopy. PMID- 17272191 TI - A respiration monitor based on electrocardiographic and photoplethysmographic sensor fusion. AB - Respiratory variations are present in the pulse wave transit time (PTT) and, as a consequence of respiratory sinus arrhythmia, in the electrocardiogram (ECG) and the photoplethysmogram (PPG). The aim of this study was to investigate these variations in healthy subjects during rest and invoked blood pressure changes. The primary goal was to develop a non-invasive respiration monitor. The error rates for breath detection during rest were 14%, 11% and 10% for PTT, ECG and PPG respectively. Significantly higher error rates were found in hypotension and hypertension. To improve accuracy and robustness, the signals were merged in a neural network resulting in an error rate of 9%. PMID- 17272192 TI - Laser Doppler method in evaluation of vasovagal syncope induced by tilt table test. AB - The laser Doppler flowmetry offers a new noninvasive, real-time technique for monitoring of the blood perfusion in living tissue. In spite of some instrumental problems, e.g. relative calibration and unknown sampling measurement depth, this method has already been used in clinical examination. The purpose of presented study was the application of the laser Doppler method in evaluation of the vasovagal syncope induced in the tilt-table test. Twelve patients with the history of syncopal episodes were examined using the head-up tilt-table test. In the some condition three normal subjects were also examined as the reference. Results of examination have showed that the changes measured by laser Doppler method are clearly visible during the pre-syncope and syncope period. These changes in perfusion precede the subjective clinical symptoms as well as decrease in the blood pressure, blood oxygen saturation and heart rate. PMID- 17272193 TI - Direct coextensive plethysmography for non-invasive measurement of systemic pressures and volumes. AB - A method for noninvasive measurement of pressures and fluid volumes of the complete systemic vascular circuit, called direct coextensive plethysmography, is proposed. This includes the pressures of the large veins, small veins, venules, capillaries, arterioles, small arteries, large arteries and nonvascular fluid compartments. It uses a conventional pressure cuff on the outside of the arm, combined with a tetrapolar bioimpedance electrode band to derive a fluid volume indication (impedance) versus pressure profile for the entire system. Determination of state changes in the residual fluid volume versus pressure profile yields physiologic information about the pressures and fluid volumes in the various segments of the vascular circuit and nonvascular fluid compartments. Advanced signal processing techniques have been applied to improve upon early slope change analysis. Initial confirmation of the correlation between the measured large vein pressure and the central venous pressure were made in a small clinical trial with intensive care unit subjects. PMID- 17272194 TI - Brain electrical impedance at various frequencies: the effect of hypoxia. AB - Non-invasive multi-frequency measurements of transcephalic impedance, both reactance and resistance, can efficiently detect cell swelling of brain tissue and can be used for early detection of threatening brain damage. We have performed experiments on piglets to monitor transcephalic impedance during hypoxia. The obtained results have confirmed the hypothesis that changes in the size of cells modify the tissue impedance. During tissue inflammation after induced hypoxia, cerebral tissue exhibits changes in both reactance and resistance. Those changes are remarkably high, up to 71% over the baseline, and easy to measure especially at certain frequencies. A better understanding of the electrical behaviour of cerebral tissue during cell swelling would lead us to develop effective non-invasive clinical tools and methods for early diagnosis of cerebral edema and brain damage prevention. PMID- 17272196 TI - A low-cost optical pachymeter for the diagnosis of glaucoma and ocular hypertension. AB - Glaucoma and ocular hypertension are major causes of vision loss worldwide. Recent clinical studies have highlighted the importance of central corneal thickness in diagnosing these disorders. However, current instrumental methods of measuring corneal thickness are not ideal for widespread clinical deployment. Here we compare the existing state of the art in corneal pachymetry with a novel, simple optical technique that will allow for the use of corneal pachymetry as a diagnostic tool in a non-research clinical setting. PMID- 17272195 TI - Continuous blood pressure monitoring utilizing a CMOS tactile sensor. AB - A novel tactile device based on a monolithically integrated sensor chip is presented for external blood pressure measurement. It uses a tonometric principle, thus allowing for continuous monitoring of the blood pressure without the need for an invasive catheter. On the chip, the deflection of membranes in an array is sensed capacitively and read out using a SigmaDelta-modulator. The membrane array and the modulator are fabricated on a single chip using an industrial CMOS (complementary metal oxide semiconductor) technology combined with post-process micromachining to achieve small and portable devices with low power consumption. The tested device is operated at a conversion rate of 1 kilosamples per second and is pressure biased to a 2000 hPa (1500 mmHg) reference point. The power consumption of the sensor chip is 11.5 mW with signal-to-noise ratio better than 72 dB. During testing a pressure resolution of approximately 8 hPa (6 mmHg) for one digit at the output of the SigmaDelta-modulator is achieved over the range of interest continuous blood pressure monitoring using this CMOS based tactile device is successfully demonstrated. The characteristic features of a blood pressure waveform are clearly recognizable from the acquired data. PMID- 17272197 TI - Measurement of airflow through a metered dose inhaler during MRI. AB - We designed, calibrated and tested a flow meter for use inside an MRI scanner for measuring airflow through a metered dose inhaler (MDI). Several flow measurement methods were analyzed and the differential pressure method was selected utilizing the inhaler as part of the sensor. Our system can measure respiratory flows during use enabling the relationships between flow rate, air flow resistance, inhaler design, and drug deposition to be measured. PMID- 17272198 TI - Visualization of lumbar muscle contraction synergy using surface electromyography (sEMG) streaming topography. AB - Because of the difficulty in analysis and interpretation of surface electromyography (sEMG), the specific muscle contraction synergy associated with low back pain continues to be debated. Streaming topography is a novel method of continuously visualizing the distribution of sEMG signals during dynamic motion to provide a more comprehensive examination and subsequent insight into the synergy of muscle recruitment pattern. The purpose of this study was to assess the feasibility of streaming topography as a diagnostic tool. Ten healthy subjects were recruited to establish the normal pattern of lumbar muscle activity. An array of surface EMG electrodes was applied to the low back region and recorded during forward bending. The root mean square (RMS) of the sEMG signals were calculated as a function of both position and time to produce streaming topographical videos of the muscle activity in the lumbar region. In addition, a preliminary clinical study was carried out with 3 LBP patients. In normal subjects, RMS streaming topography was consistent, reproducible, and reliable. In clinical observation, the RMS streaming topography of LBP patients was obviously different from that of normal subjects. Some of LBP patients showed an asymmetric distribution during symmetric action. Streaming topography provides a dynamic analysis of lumbar muscle activities and illustrates the synergy of muscle contractions, which may be useful to improve physiotherapy management of LBP. PMID- 17272199 TI - A low cost Doppler system for vascular dialysis access surveillance. AB - The National Kidney Foundation guidelines for vascular access recommend access surveillance to avoid morbidity among patients undergoing hemodialysis. Methods to detect access failure based on CW Doppler system are being proposed to implement surveillance programs at lower cost. This work describes a low cost Doppler system implemented in a PC notebook designed to carry out this task. A Doppler board samples the blood flow velocity and delivers demodulated quadrature Doppler signals. These signals are sampled by a notebook sound card. Software for Windows OS (running at the notebook) applies CFFT to consecutive 11.6 ms intervals of Doppler signals. The sonogram is presented on the screen in real time. The software also calculates the maximum and the intensity weighted mean frequency envelopes. Since similar systems employ DSP boards to process the Doppler signals, cost reduction was achieved. The Doppler board electronic circuits and routines to process the Doppler signals are presented. PMID- 17272200 TI - Evanescent cavity ring-down spectroscopy (e-CRDS) of hemoglobin absorption at the silica-water interface. AB - The absorption of hemoglobin (Hb) from controlled urine samples was observed using the technique of evanescent cavity ring-down spectroscopy (e-CRDS). A room temperature, alexandrite laser pumped LiF:F2(+**) color-center pulsed laser was used to excite Hb at 425 nm. A minimum absorbance level of 2.57 x 10(-4) was achieved corresponding to a minimum detectable concentration of Hb in urine of 5.8 nM. These levels could have advantages in the diagnosis of hemoglobinurea. The formation of layers of Hb upon the silica surface allowed for an increased sensitivity for smaller concentrations of Hb than would be expected for only a free floating solution. The formation of the layers also suggested a higher binding constant of Hb to the silica surface than between other layers of Hb molecules. Future studies are underway to understand the effects of salinity on the observed absorption due to the competitive binding of Na+ to the surface. Absorption isotherm modeling will also be used to better understand the development of layers upon the surface. PMID- 17272201 TI - Litigation in obstetrics: a lesson learnt and a lesson to share. AB - A perfect baby is the expectation of all parents, and a perfect outcome is the mission of obstetrics. Every obstetrician dreads to hear that there is an unexpected maternal mortality and/or severe fetal injury at the hospital. The role of a perceived public expectation of perfection in obstetric medicine reflects a belief that bad outcomes in obstetrics should not be tolerated and that every maternal-fetal injury merits financial compensation and punishment. What has brought these troubling times to obstetric medicine? The drivers behind malpractice crises are the four leading interest groups in the medical-legal debate: pregnant patients and their environment (husband, parents, relatives, friends, legislators, and the media), health-care providers, insurance companies, and trial attorneys. Litigation in obstetrics is the result of a complex of events when malpractice (presumed or real) impacts on the attitude of pregnant women and their environment. In such complexity, information is mandatory but may often be misinterpreted. If messages are not tailored to the receiver's capacity, communicating well with the pregnant patient becomes crucial. Therefore, to reduce medical-legal issues in obstetrics, increasing attention and an applicable standard of obstetric care to avoid negligence and medical errors should go along with better communication with pregnant women. Communication should be clear, targeted, effective, flexible, and empathic to share a common language and decisions. This review briefly presents and discusses some of the most frequently encountered medical-legal claim cases in obstetric practice. In-depth review of pregnancy-related deaths and major morbidities can help determine strategies needed to continue making pregnancy safer. PMID- 17272202 TI - Clinical potential for noninvasive prenatal diagnosis through detection of fetal cells in maternal blood. AB - Fetal cells circulate in maternal blood and are considered a suitable means by which to detect fetal genetic and chromosomal abnormalities. This approach has the advantage of being noninvasive. Since the early 1990s, nucleated erythrocytes (NRBCs) have been considered good target cells for a number of techniques, including fluorescence-activated cell sorting and magnetic cell sorting, using antibodies such as anti-transferrin receptor and anti-gamma-hemoglobin antibodies, followed by analysis with fluorescence in situ hybridization or polymerase chain reaction. In the late 1990s, the National Institute of Child Health and Human Development Fetal Cell Isolation Study assessed the reliability of noninvasive prenatal diagnosis of fetal aneuploidy using NRBCs isolated from maternal circulation. This study revealed the limitations of NRBC separation using antibodies specific for NRBC antigens. A more recent study has demonstrated the efficiency and success of recovery of NRBCs using a galactose-specific lectin, based on the observation that erythroid precursor cells have a large quantity of galactose molecules on their cell surface. Thus, recent advances in this field enhance the feasibility of this diagnostic method. This review article focuses on various methods of detection of fetal cells within the maternal circulation, as well as the status of previous and current studies and the prospective view for noninvasive prenatal diagnosis using fetal cells from the maternal circulation. PMID- 17272203 TI - Velamentous cord insertion: significance of prenatal detection to predict perinatal complications. AB - In the maternal and child health statistics of Japan for 2003, perinatal deaths were most frequent in pregnant women with abnormalities of the placenta, umbilical cord, and fetal membrane. Despite advances in perinatal medicine, approximately 2% of low-risk pregnant women still require an emergency cesarean section after the onset of labor. Because it is likely that half of these cases are associated with placental and umbilical cord abnormalities, it is thought that prenatal detection of such abnormalities would reduce the number of emergency cesarean sections in low-risk women. In our previous studies, some abnormalities of the placenta and umbilical cord were associated with abnormalities of cord insertion. Furthermore, we reported that prenatal detection of velamentous cord insertion (VCI) reduced the number of emergency cesarean sections in low-risk women. In this review, we describe the prenatal detection of abnormalities of umbilical cord insertion and the management of VCI based on our current clinical data. PMID- 17272204 TI - SELDI-TOF MS profiling of plasma proteins in ovarian cancer. AB - OBJECTIVE: Proteomic profiling of plasma or serum is a technique to identify new biomarkers in disease. The objective of this study was to identify new plasma biomarkers in ovarian cancer patients using mass spectrometry protein profiling and artificial intelligence. METHODS: A total of 65 plasma samples obtained from women with ovarian cancer (n = 35) and age-matched disease-free controls (n = 30) were applied to anion exchange protein chips for protein profiling by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). RESULTS: SELDI-TOF MS was highly reproducible in detecting ovarian tumor specific protein profiles. One protein peak (relative molecular mass, Mr, 11,537 Da) was identified in plasma from women with ovarian cancer but not in controls. Two peaks, Mr 5,147 and 8,780 Da, were present in the plasma of controls but not of women with ovarian cancer. After a training analysis, classification analysis generated by univariant or linear combination split was performed to reach a discriminant protein signature pattern. After cross validation, a sensitivity of 84% and specificity of 89% for all studied cases and controls was reached. CONCLUSION: This study clearly demonstrates that the combined technology of SELDI TOF MS and artificial intelligence is effective in distinguishing protein expression between normal and ovarian cancer plasma. The identified protein peaks may be candidate proteins for early detection of ovarian cancer or evaluation of therapeutic response. PMID- 17272205 TI - Are there any predictors for failed Burch colposuspension? AB - OBJECTIVE: To investigate early postoperative complications of Burch colposuspension and the risk factors that may be associated with failure. METHODS: We retrospectively reviewed the chart records of all patients who underwent Burch colposuspension from October 1997 to September 2002. Indications for colposuspension included urodynamic stress incontinence with bladder neck hypermobility and adequate vaginal capacity. The occurrence of early postoperative complications related to the operation was documented. Subjective failure of the operation was defined as patient dissatisfaction and/or persistent urinary leakage. Chi-square test or Fisher's exact test was used to determine the association among risk factors, early postoperative complications, and the failure rate of Burch colposuspension. RESULTS: A total of 258 patients (92.5%) reported satisfaction with the surgical outcome. The age, parity, menopausal status, use of hormone replacement therapy, previous hysterectomy, and occurrence of early postoperative complications did not significantly influence the failure rate. CONCLUSION: Our results demonstrate that Burch colposuspension is an effective and, according to our patients, highly satisfactory procedure for the treatment of urodynamic stress incontinence. PMID- 17272206 TI - Detection of chromosome aberrations in the second trimester using genetic amniocentesis: experience during 1995-2004. AB - OBJECTIVE: To retrospectively investigate the 10-year experience of prenatal diagnosis of fetal chromosome aberrations by second-trimester amniocentesis. METHODS: Data were collected at Taichung Veterans General Hospital between 1995 and 2004 from cytogenetic analyses of cultured amniocytes from second-trimester amniocentesis. The main indications for amniocentesis included advanced maternal age, abnormal maternal serum screening results, and abnormal ultrasound findings. Chromosome aberrations included autosomal aneuploidies, sex chromosome aneuploidies, polyploidies, and rearrangements. Variant chromosomes were considered to be normal and excluded. RESULTS: A total of 7,028 amniocenteses were performed and analyzed for chromosome aberrations. Among these, 4,026 (57.29%) were for advanced maternal age, 1,500 (21.34%) for abnormal maternal serum screening results, 553 (7.87%) for abnormal ultrasound findings, and 949 (13.50%) for other reasons. The highest detection rate of chromosome aberrations was in cases undergoing amniocentesis for abnormal ultrasound findings (8.86%), followed by other reasons (2.74%), abnormal maternal serum screening results (2.60%), and advanced maternal age (2.31%). Chromosome aberrations were detected in 207 cases (2.90%), including fetuses of 93 older mothers, 39 mothers with abnormal serum screening results, 49 mothers with abnormal ultrasound findings, and 26 mothers with other reasons for amniocentesis. Of fetuses with chromosome aberrations, 144 (69.56%) had trisomy 13, trisomy 18, trisomy 21, or sex chromosome disorder. The other 63 cases (30.44%) included balanced translocation, unbalanced abnormality, inversion, and marker chromosome. CONCLUSION: For daily practice, our data could offer a database for proper genetic counseling, such as termination issues and future pregnancies. PMID- 17272207 TI - Impact of the menstrual cycle on immunologic markers in HIV-infected Taiwanese women. AB - OBJECTIVE: This study tested the relationship between cellular immunity and the menstrual cycle in Taiwanese HIV-infected and normal women. METHODS: From October 1997 to October 2001, 21 HIV-seropositive women and 30 controls were enrolled in this study. Blood was sampled for hormone profile (estradiol and progesterone) and immunophenotyping with flow cytometry during the follicular and luteal phases. Immunophenotyping included total blood cell count, lymphocyte count, CD4+ cells, CD8+ cells, and their activation markers, including CD25, CD69, HLA-DR, and CD38. RESULTS: The proportion of CD8+ T cells increased during the follicular phase and activating antigens (HLADR and CD38) were elevated on CD8+ T cells of HIV-seropositive women. All these alterations seemed unrelated to the menstrual cycle. CONCLUSIONS: The CD8+ T cells were increased and activated in women with HIV infection but these alterations were not affected by the menstrual cycle. Therefore, sex hormones seem not to affect the course of HIV infection. PMID- 17272209 TI - Prenatal sonographic features of hypospadia: two- and three-dimensional findings. AB - OBJECTIVE: To present our experience of applying three-dimensional ultrasonography in prenatal diagnosis of hypospadia. CASE REPORT: A 28-year-old woman, gravida 1, para 0, visited our hospital at 17 weeks' gestation. No gross anomaly was found on the scan at 21 weeks' gestation. Fetal growth was appropriate for gestational age on two-dimensional (2D) ultrasonography at 27 weeks' gestation, but an abnormally curved and shortened fetal penis was found incidentally. Three-dimensional (3D) imaging in surface-rendered mode was used to reconstruct the fetal penis. Multiplanar and surface-rendered images were obtained in the midsagittal, axial, and coronal planes to precisely delineate the ventral curvature of the penis. At 39 weeks' gestation, a term newborn was delivered by vacuum extraction. On examination, the fetus was confirmed to have hypospadia. Karyotyping revealed 46,XY. CONCLUSION: 2D ultrasonography could only give indirect clues of hypospadia that was later more precisely delineated by 3D ultrasonography in surface-rendered mode. PMID- 17272208 TI - Monitoring medical abortion using mifepristone/misoprostol combination with ultrasonogram and serum human chorionic gonadotropin. AB - OBJECTIVE: The oral mifepristone/misoprostol combination (MMC) is safe for medical abortion in early pregnancy. The abortion status in MMC-treated pregnancies at Taipei Medical University-Wan Fang Medical Center was determined by ultrasonography, serum beta-human chorionic gonadotropin (beta-HCG), and histopathology. METHODS: All women at less than 49 days since the last menstruation who asked for legal abortion were evaluated by ultrasonography. They then received 600 mg of oral mifepristone followed 48 hours later by 600 microg of misoprostol. Women who had vaginal spotting or bleeding after 14 days were included in this study and underwent transvaginal ultrasonography, serum beta-HCG measurement and vacuum aspiration or therapeutic dilatation and curettage (D&C) on day 14. Specimens were identified by histopathology. Abortion status was determined from linear regression of serum beta-HCG and endometrial thickness. RESULTS: Of 35 women who underwent vacuum aspiration or therapeutic D&C, histopathology showed that 20 had decidual tissue and 15 had gestational tissue. Logistic regression showed that the distance measurement to the logistic regression line differed significantly between complete and incomplete abortion (p < 0.05). CONCLUSION: In this study, serum beta-HCG assays in addition to ultrasonographic evaluation helped to discriminate abortion status after oral MMC. PMID- 17272210 TI - Prenatal 2D ultrasonic diagnosis of fetal complete atrioventricular block and bilateral hydroceles with occult maternal SS-A. AB - OBJECTIVE: We present a case of fetal complete atrioventricular block, diagnosed by the M mode of two-dimensional ultrasound, that was complicated with polyhydramnios and bilateral hydrocele. CASE REPORT: The fetus was delivered at 38 weeks' gestation by caesarean section. Postpartum autoimmune survey disclosed positive anti-Ro antibodies (SS-A) for both the mother and the newborn. Severe neonatal bradycardia with complete atrioventricular block was identified. CONCLUSION: Antenatal evaluation for a maternal history of autoimmune disease (especially systemic lupus erythematosus) and prevention of fetal bradycardia by reducing immune-mediated injuries on the cardiac conduction system are important. PMID- 17272211 TI - Familial premature ovarian failure in female premutated carriers of fragile X syndrome: a case report and literature review. AB - OBJECTIVE: The fragile X syndrome is the most common form of familial mental retardation. Most males with the FMR1 full mutation function in the mentally retarded range of intelligence. In contrast, females with the FMR1 full mutation show a broader range of intelligence. The most impressive somatic involvement that is consistently found among only premutated carrier females, not full mutation carriers, is premature ovarian failure (POF). CASE REPORT: We report a family of fragile X syndrome. All six daughters had POF and both of the grandsons born to the daughters showed mental retardation. CONCLUSION: We concluded that there was an association between fragile X syndrome premutation and POF, and established a model mechanism to explain the relationship. PMID- 17272212 TI - Septic shock after conservative management for placenta accreta. AB - OBJECTIVE: The rate of placenta accreta has risen in the last three decades due to the increasing rate of cesarean section. Placenta accreta usually results in severe postpartum hemorrhage requiring massive blood transfusion and postpartum hysterectomy. Conservative treatment is an alternative in selected patients to preserve fertility and decrease postpartum hemorrhage, but the risks of conservative treatment have seldom been described. CASE REPORT: A 39-year-old woman with placenta accreta diagnosed during cesarean section was treated conservatively. Persistent puerperal fever with leukocytosis developed during the postpartum period in spite of long-term antibiotic treatment. Evacuation of the retained placenta resulted in septic shock, which occurred immediately after dilatation and curettage. An uneventful recovery was achieved after use of strong antibiotics and fluid challenge. CONCLUSION: At present, there is no consensus about the optimal treatment for placenta accreta. Conservative treatment appears to be an alternative in selected patients, but the complications such as sepsis should be carefully identified and appropriately managed. PMID- 17272213 TI - Combined diverticulectomy and anti-incontinence surgery for patients with urethral diverticulum and stress urinary incontinence: is anti-incontinence surgery really necessary? AB - OBJECTIVE: Urethral diverticulum has been identified in 0.6-6% of women and is diagnosed most frequently in the third to fifth decades. Combined diverticulectomy and anti-incontinence surgery are usually undertaken for patients with urethral diverticulum who present with symptoms of stress urinary incontinence. However, this approach may not always be necessary. CASE REPORT: We report two cases with urethral diverticulum and stress urinary incontinence successfully treated with diverticulectomy only. CONCLUSION: This clinical approach could avoid the potential complications of anti-incontinence surgery. PMID- 17272215 TI - Umbilical cord stricture causing intrauterine fetal death in a 22-week fetus. AB - OBJECTIVE: Umbilical cord stricture is an uncommon but distinctive condition associated with intrauterine fetal death. Although cases have been reported periodically since the last century, there has been considerable speculation as to whether the condition is real or a postmortem artifact. CASE REPORT: A 27-year old woman, G2P0SA0AA1, was diagnosed with intrauterine fetal death at 22 weeks' gestation. The dead fetus with Apgar score 0'->0' was delivered. The cord was twisted at the insertion site of the umbilicus. Neither growth restriction nor anatomic abnormalities were noted. CONCLUSION: Although the risk of recurrence has generally been thought to be low in the past, patients with a demise attributed to umbilical cord stricture should be counseled. The mechanism of cord stricture and how it leads to fetal death remain unknown. If the exact etiology of cord stricture can be determined, efforts may be directed at preventing a recurrence. Additional published cases may be helpful. PMID- 17272214 TI - Persistent megalocystic ovary following in vitro fertilization in a postpartum patient with polycystic ovarian syndrome. AB - OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is more severe when pregnancy occurs, as the developing pregnancy produces human chorionic gonadotropin, which stimulates the ovary's persistent growth. If no pregnancy occurs, the syndrome will typically resolve within 1 week. In a maintained pregnancy, slow resolution of symptoms usually occurs over 1-2 months. CASE REPORT: A 31-year-old woman, gravida 2, para 1, aborta 1, with polycystic ovary syndrome underwent in vitro fertilization (IVF) with clomiphene citrate and follicle-stimulating hormone/gonadotropin releasing hormone-antagonist stimulation. During transvaginal oocyte retrieval, enlarged bilateral ovaries were noted. She had an episode of OHSS after IVF/embryo transfer, for which paracentesis was performed three times. Pregnancy was achieved. Throughout antenatal examinations, bilateral ovaries were enlarged. She delivered a healthy baby by cesarean section at term. However, 1 month after delivery, the bilateral ovary had not shrunk, and levels of tumor markers CA125 and CA199 were 50.84 and 41.34 U/mL, respectively. At laparotomy for suspected malignancy, both adnexae formed "kissing ovaries", which were multinodulated with yellow serous fluid. Specimens from wedge resection submitted for frozen section showed a benign ovarian cyst. The final pathology report showed bilateral follicle cysts. CONCLUSION: With the increasing use of gonadotropins in the management of infertility, ovarian enlargement secondary to hyperstimulation is common. Generally, symptoms appear between the 6th and 13th weeks of pregnancy and disappear thereafter. The hyperstimulated ovary often subsides after the first trimester. This case is unusual as the megalocystic ovary persisted after delivery. To the best of our knowledge, we report the first case of enlarged bilateral ovaries persisting 2 months after delivery. PMID- 17272216 TI - Septic shock after intracervical laminaria insertion. AB - OBJECTIVE: Laminaria placement is seldom thought to be associated with postabortal sepsis. CASE REPORT: A nulliparous woman presented with high fever, low blood pressure, and signs of infection during artificial legal abortion with laminaria placement for cervical dilatation. Broad-spectrum antibiotics were given. Cultures of blood, placenta, and arterial line all yielded Enterobacter cloacae. The patient responded to antibiotics and supportive care. CONCLUSION: The use of laminaria still places patients at risk for infection because there is a certain risk of ascending colonization with potentially pathogenic microorganisms from the vaginal and cervical microflora, as in our patient. Surgical disinfection, prophylactic antibiotics, and shortened duration of laminaria placement are helpful to prevent infectious insult. Once signs of infection are noted, physicians should take action as soon as possible, such as initiating broad-spectrum antibiotics and intensive care. PMID- 17272217 TI - Fetal atrial flutter: a case report and experience of sotalol treatment. AB - OBJECTIVE: Fetal tachyarrhythmia may cause fetal hydrops and lead to fetal morbidity and mortality. Supraventricular tachycardia and atrial flutter have been the most diagnosed. We present a case of fetal atrial flutter diagnosed during the second trimester treated with digoxin and sotalol and delivered at term. CASE REPORT: A 30-year-old primigravid woman was diagnosed with fetal atrial flutter at the gestational age of 25 weeks with atrial rates of 480-520 bpm and ventricular rates of 200-250 bpm. Initially, she was treated with digoxin then with a combination of digoxin and sotalol. The fetal heart beat slowed after sotalol treatment but did not return to sinus rhythm. The fetus was delivered vaginally. Neonatal echocardiography showed a small apical ventricular septal defect and small patent ductus arteriosus. Electrocardiography also revealed atrial flutter with occasional atrial fibrillation. CONCLUSION: The efficacy of antiarrhythmic drug therapy for fetal atrial flutter has not been well established. In our case, we used sotalol combined with digoxin and the fetal heart beat slowed after therapy. Sotalol may be considered the drug of choice for fetal atrial flutter. If the fetal atrial flutter is resistant to these therapies, a combination of other congenital cardiac diseases or organic abnormalities should be considered. PMID- 17272219 TI - Malignant fibrous histiocytoma during pregnancy: a case report. AB - OBJECTIVE: We present a case of a 38-year-old postpartum woman who had antepartal undiagnosed sarcoma with multiple metastasis. Although the patient underwent aggressive treatment with surgery and chemotherapy, she died 3 months after the vaginal delivery of a healthy female infant weighing 2,090 g at 35 weeks of gestation. CASE REPORT: The patient had right shoulder pain and mild chest discomfort during the last trimester of the pregnancy. Six days after delivery, she came to our emergency room because her pain had become more severe. A humeral neck tumor with bone destruction was found in the right shoulder on X-ray. After detailed evaluation, right humeral surgery, cardiac surgery, and liver biopsy were performed. All the removed specimens were sent for pathologic examination, and the results showed a sarcoma favoring malignant fibrous histiocytoma with its primary origin in the left atrium. CONCLUSION: Obstetricians should be aware that any non-specific complaint may be due to severe disease. It is better to evaluate all symptoms and signs that persist. In this case, early intervention such as radiologic imaging of the bone or echocardiography could have been performed during pregnancy to prevent tumor spread, maternal morbidity, and even death. PMID- 17272218 TI - Isolated congenital diaphragmatic hernia in the third trimester: a case report and literature review. AB - OBJECTIVE: To report a rare congenital anomaly, a right diaphragmatic hernia, in a near-term baby. CASE REPORT: A 40-year-old female, gravida 3, para 2, had undergone regular prenatal care in our department since the early second trimester. She underwent amniocentesis at 16 weeks of gestation. The result showed normal 46,XY. Fetal growth was appropriate throughout the pregnancy. A small heart with marked left-side deviation was noted in the third trimester. The heart rate was less than 25% of normal. A homogenous mass with centralized vessels was noted in the fetus's right chest. The baby showed respiratory distress immediately after delivery. Imaging studies after birth proved there was a right diaphragmatic hernia with severe pulmonary hypertension and poor lung function. CONCLUSION: Right congenital diaphragmatic hernia is rare. A prenatal diagnosis is difficult to make in the second trimester. Prognosis is greatly influenced by the associated abnormalities. PMID- 17272220 TI - Ruptured tubo-ovarian abscess in a postmenopausal woman presenting with septic shock: a case report and literature review. AB - OBJECTIVE: To report a case of a ruptured tubo-ovarian abscess which induced septic shock in a postmenopausal woman. CASE REPORT: A 53-year-old postmenopausal woman was transferred to our emergency department for drowsiness, hypotension, and lower abdominal discomfort. Transabdominal sonography and computed tomography showed a large pelvic tumor over the left adnexa with some ascites. The uterus and other adnexa were unremarkable. Laboratory data, including blood count and electrolytes, showed leukocytosis and azotemia. Under suspicion of a ruptured adnexal tumor, laparotomy was performed and showed a large ruptured tubo-ovarian tumor arising from the left adnexa with intra-abdominal pus formation. Subtotal hysterectomy and bilateral salpingo-oophorectomy led to massive bleeding during manipulation of the left adnexa because of the necrotic change in the left infundibulopelvic vessels. Deep vein thrombosis and wound disruption occurred after the operation, but, fortunately, she recovered 1 month later. CONCLUSION: Tubo-ovarian abscesses in postmenopausal women are uncommon but should be kept in mind with a pelvic tumor accompanied by septic shock, as this may cause a terrible outcome and other sequelae. PMID- 17272223 TI - The atomic world and cancer. PMID- 17272221 TI - Phantom HCG and clinical management. PMID- 17272224 TI - Molecular biology of bladder cancer. AB - Bladder cancer is a major cause of health expenses and it presents formidable clinical challenges. Two types of tumors have been identified, papillary and non papillary. The former are mainly characterized by FGFR3 and chromosome 9 alterations and a low frequency of Tp53 alterations. The latter are characterized by a high frequency of alterations in genes in the p53 and Rb pathways. Chromosome 9 alterations, specially in 9q, are crucial to bladder cancer development and occur in both types of tumors. Progression of some superficial tumors (mainly TaG3 and T1G3) to high-grade, invasive, carcinomas provides evidence of some overlap between the two pathways. Distinct gene expression profiles have been identified in superficial and invasive tumors. The stage is now ready for the clinical application of this knowledge. PMID- 17272225 TI - Tumour cells resistance in cancer therapy. AB - Resistance to chemotherapeutic drugs presents a big caveat for cancer treatment. In this review we will describe the molecular mechanisms involved in chemoresistance, discussing the mechanisms of resistance related to tumour microenvironment, as well as their intracellular mechanisms. Chemoresistance can also appear as a consequence to treatments with new anticancer drugs. In this sense, we will exemplify this type of resistance discussing mechanisms of action of epidermal growth factor receptor (EGFR) inhibitors. We conclude that the main problem of chemoresistance is due to its pleiotropic and multifactorial nature. PMID- 17272226 TI - Hypofractionation in radiotherapy. AB - Major changes in cancer radiotherapy have followed a greater understanding of the biological effects of radiation on tumours and normal tissues. Clinical radiotherapy is today a solid body of knowledge with well defined scientific foundations. Key concepts in current radiobiology include lethal and sublethal injuries, dose-effect coefficients, alpha/beta ratios, acute and late response, biologically equivalent dose, fraction dose, irradiation time and tumour regeneration between others. Effects of irradiation time and dose per fraction on tumours versus normal tissues are of special importance. Dose per fraction must be considered for analysis of effects in normal late-responding tissues. In contrast, both dose per fraction and irradiation time influence the response to radiation of malignant tumours and acute-responding tissues. Finally, the ability to quantify relationships between radiation dose and biological effect has been of particular value in the development of radiotherapy. This is illustrated by the growing use of high doses per fraction for the treatment of some cancers. PMID- 17272227 TI - The role of radiotherapy for prevention of heterotopic ossification after major hip surgery. AB - Heterotopic ossification or ectopic bone formation represents a widely known complication after surgery involving joint spaces. Posttraumatic heterotopic ossification can be found at any site. The most common postsurgical site is the hip following total hip arthroplasty. This review explores the treatment options to prevent ectopic bone formation after major surgery of hip, especially, the role of radiotherapy. PMID- 17272228 TI - Diagnosis efficacy of structural (CT) and functional (FDG-PET) imaging methods in the thoracic and extrathoracic staging of non-small cell lung cancer. AB - PURPOSE: To evaluate the efficacy of FDG-PET in the definition of tumour lung node lesions and to compare the diagnostic validity of CT and FDGPET in the staging of patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with clinical suspicion of potentially resectable NSCLC (n = 108) were studied by standard procedures in our setting, including fibrobronchoscopy, transthoracic fine-needle aspiration, thoracoabdominal CT and FDG-PET. PET images were analysed by researchers blinded to results of other imaging modalities. Definitive tumour diagnosis was by histopathological study in patients who underwent surgery and by specific imaging methods and biopsy, when available, in patients who did not. Diagnostic accuracy was evaluated by comparing CT/PET results with the definitive diagnosis. RESULTS: In 13% of patients, no FDG-PET findings were observed and the histological study was negative for tumour. In 22% of patients, FDG-PET detected metastatic disease (M0 by CT). For mediastinal involvement, global diagnostic accuracy was 0.90 with FDG PET and 0.59 with CT. False positive FDG-PET findings were produced by inflammatory conditions and false negative findings by the small size or proximity of lymph nodes to primary tumour. Mediastinal staging by CT and FDG-PET was correct in 56% and 87% of patients, respectively. CT indicated mediastinal invasion in 17% of patients with no FDG-PET finding of mediastinal involvement. Conversely, mediastinal spread was undetected by CT in 14% of patients with FDG PET findings of mediastinal involvement. CONCLUSIONS: Although complementary, the functional method (FDG-PET) is significantly superior to the structural method (CT) for detection of mediastinal tumour disease. PMID- 17272230 TI - Clinical outcome after surgical resection of lung metastases from melanoma. AB - BACKGROUND: Surgical therapy plays an important role in the management of selected patients with metastatic melanoma. PURPOSE: A retrospective review of 13 patients who underwent surgical resection of lung metastases from melanoma from 1996 to 2003 was performed. The aim of the study was to analyze the clinical outcome and survival time. MATERIALS AND METHODS: Mean age was 45 years old (range: 31-64). Complete tumour resection was confirmed histologically. Nine patients presented one single pulmonary lesion, two lesions (n = 3) and three lesions (n = 1) but in all cases confined in the same pulmonary lobe. RESULTS: Median survival time (MST) for the entire group was 20 months (95% confidence interval (CI): 16-24 months). The median time to disease progression after lung metastasectomy was 5 months (95% CI: 3-7 months). MST, according to the prognostic groups proposed by the International Registry of Lung Metastases, was 17 months (95% CI: 6-28 months) for group I (n = 6), MST of 20 months (95% CI: 16 24 months) for group II (n = 5) and MST of 4 months for group III (n = 2), without differences statistically significant (log-rank p = 0.423). MST regarding the time of disease free interval from diagnostic of primary tumour and lung metastases (< 36 months [n = 5] vs > 36 months [n = 8]) was 20 months and 17 months respectively, without differences statistically significant (log rank p = 0.222). CONCLUSIONS: Surgical resection when feasible provides survival rates superior to any available nonsurgical therapy. In carefully selected patients, when the resection is performed with curative intent, it may result in improved survival. PMID- 17272229 TI - Long term results of a phase II trial of induction chemotherapy with uracil ftegafur (UFT), vinorelbine and cisplatin (UFTVP) followed by radiotherapy concomitant with UFT and carboplatin (RT/UFTJ) in non-resectable locally advanced (stage IV-B) squamous cell head and neck carcinoma and peripheral blood stem cell support (PBSCS) with febrile neutropenia. AB - PURPOSE: To evaluate the response of advanced squamous cell head and neck carcinoma to a combination of induction chemotherapy and radiotherapy. METHODS: We present long-term results of a phase II trial of Induction Chemotherapy with UFT 200 mg/m(2) p.o. days 1 to 21, Vinorelbine 25 mg/m(2) i.v. days 1 and 8 and Cisplatin 100 mg/m(2) i.v. day 1 (UFTVP) each 21 days for 4 courses, followed by Radiotherapy concomitant with UFT 100 mg/m(2) p.o. daily and Carboplatin AUC = 0.5 i.v. weekly (RT/UFTJ) in patients (pts) with Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma (IV-B-SCHNC). Primary endpoint was Complete Response to induction UFTVP and secondary endpoints were Disease Free Status Rate after locoregional treatment and long-term Overall Survival. Between 1994 and 1997, 32 pts were included. RESULTS: Complete Response to Induction UFTVP was 59% (95% CI: 48%-70%). Main toxicity of UFTVP was G 3,4 neutropenia (94% of pts; 25% developed febrile neutropenia and 1 of this pts dead). After Induction Chemotherapy with UFTVP, 30 pts received radiotherapy and 25 of them received concomitant Carboplatin and UFT (RT/UFTJ): main toxicity was mucositis (G3-4: 72%) and one patient died during RT/UFTJ because pneumonia. Twenty-five pts (78%) were alive and disease free at the end of the whole treatment. Actuarial 5 year Overall survival is 32%. CONCLUSION: Although toxicity is important, this approach has interesting activity and deserves further investigation. PMID- 17272231 TI - Panhypopituitarism as first manifestation of a lung cancer. AB - Pituitary metastases of solid tumours are infrequent, specially as a first manifestation. When they happen, they are usually due to breast or lung cancer and are asymptomatic or produce diabetes insipidus. It is very strange that they produce hormonal deficiency. We present a case report of a bronchogenic adenocarcinoma in a 65-year-old man which began with panhypopituitarism, diabetes insipidus and visual alterations. Magnetic resonance imaging revealed a large sellar mass, with clivus infiltration and invading the right cavernous sinus. The biopsy result was adenocarcinoma metastases from lung cancer. PMID- 17272232 TI - Value of third metastasectomy of colorectal adenocarcinoma. AB - 62 year-old woman with a tumour in sigmoid colon invading left ovary and metastases in both hepatic lobes. Posterior pelvic exanteration and metastasectomy of left hepatic lesions were performed in the first surgery, right hepatectomy in the second one and metastasectomy of 2 new metastases in the third one. A new metastases in remanent portal pediculum was considered non-operable. The patient died 29 months after first surgery. PMID- 17272233 TI - Superficial thrombophlebitis as an exceptional complication of a scrotal arteriovenous malformation. PMID- 17272234 TI - Genetically enhanced growth causes increased mortality in hypoxic environments. AB - Rapid growth and development are associated with several fitness-related benefits. Yet, organisms usually grow more slowly than their physiological maximum, suggesting that rapid growth may carry costs. Here we use coho salmon (Oncorhynchus kisutch) eggs of wild and transgenic genotypes to test whether rapid growth causes reduced tolerance to low levels of oxygen (hypoxia). Eggs were exposed to four different durations of hypoxia, and survival and growth were recorded until the end of the larval stage. Survival rates decreased with increasing duration of hypoxia, but this decrease was most pronounced for the transgenic group. Larval mass was also negatively affected by hypoxia; however, transgenic genotypes were significantly larger than wild genotypes at the end of the larval stage. Oxygen can be a limiting factor for survival and development in a wide range of organisms, particularly during the egg stage. Thus, the reduced ability of fast-growing genotypes to cope with low oxygen levels identified in the present study may represent a general constraint on evolution of rapid growth across taxa. PMID- 17272235 TI - Hydrogen energy. AB - The problem of anthropogenically driven climate change and its inextricable link to our global society's present and future energy needs are arguably the greatest challenge facing our planet. Hydrogen is now widely regarded as one key element of a potential energy solution for the twenty-first century, capable of assisting in issues of environmental emissions, sustainability and energy security. Hydrogen has the potential to provide for energy in transportation, distributed heat and power generation and energy storage systems with little or no impact on the environment, both locally and globally. However, any transition from a carbon based (fossil fuel) energy system to a hydrogen-based economy involves significant scientific, technological and socio-economic barriers. This brief report aims to outline the basis of the growing worldwide interest in hydrogen energy and examines some of the important issues relating to the future development of hydrogen as an energy vector. PMID- 17272236 TI - Impact of enhanced geothermal systems on US energy supply in the twenty-first century. AB - Recent national focus on the value of increasing US supplies of indigenous renewable energy underscores the need for re-evaluating all alternatives, particularly those that are large and well distributed nationally. A panel was assembled in September 2005 to evaluate the technical and economic feasibility of geothermal becoming a major supplier of primary energy for US base-load generation capacity by 2050. Primary energy produced from both conventional hydrothermal and enhanced (or engineered) geothermal systems (EGS) was considered on a national scale. This paper summarizes the work of the panel which appears in complete form in a 2006 MIT report, 'The future of geothermal energy' parts 1 and 2. In the analysis, a comprehensive national assessment of US geothermal resources, evaluation of drilling and reservoir technologies and economic modelling was carried out. The methodologies employed to estimate geologic heat flow for a range of geothermal resources were utilized to provide detailed quantitative projections of the EGS resource base for the USA. Thirty years of field testing worldwide was evaluated to identify the remaining technology needs with respect to drilling and completing wells, stimulating EGS reservoirs and converting geothermal heat to electricity in surface power and energy recovery systems. Economic modelling was used to develop long-term projections of EGS in the USA for supplying electricity and thermal energy. Sensitivities to capital costs for drilling, stimulation and power plant construction, and financial factors, learning curve estimates, and uncertainties and risks were considered. PMID- 17272237 TI - Photovoltaic and photoelectrochemical conversion of solar energy. AB - The Sun provides approximately 100,000 terawatts to the Earth which is about 10000 times more than the present rate of the world's present energy consumption. Photovoltaic cells are being increasingly used to tap into this huge resource and will play a key role in future sustainable energy systems. So far, solid-state junction devices, usually made of silicon, crystalline or amorphous, and profiting from the experience and material availability resulting from the semiconductor industry, have dominated photovoltaic solar energy converters. These systems have by now attained a mature state serving a rapidly growing market, expected to rise to 300 GW by 2030. However, the cost of photovoltaic electricity production is still too high to be competitive with nuclear or fossil energy. Thin film photovoltaic cells made of CuInSe or CdTe are being increasingly employed along with amorphous silicon. The recently discovered cells based on mesoscopic inorganic or organic semiconductors commonly referred to as 'bulk' junctions due to their three-dimensional structure are very attractive alternatives which offer the prospect of very low cost fabrication. The prototype of this family of devices is the dye-sensitized solar cell (DSC), which accomplishes the optical absorption and the charge separation processes by the association of a sensitizer as light-absorbing material with a wide band gap semiconductor of mesoporous or nanocrystalline morphology. Research is booming also in the area of third generation photovoltaic cells where multi-junction devices and a recent breakthrough concerning multiple carrier generation in quantum dot absorbers offer promising perspectives. PMID- 17272238 TI - Biological solar energy. AB - Through the process of photosynthesis, the energy of sunlight has been harnessed, not only to create the biomass on our planet today, but also the fossil fuels. The overall efficiency of biomass formation, however, is low and despite being a valuable source of energy, it cannot replace fossil fuels on a global scale and provide the huge amount of power needed to sustain the technological aspirations of the world population now and in the future. However, at the heart of the photosynthetic process is the highly efficient chemical reaction of water splitting, leading to the production of hydrogen equivalents and molecular oxygen. This reaction takes place in an enzyme known as photosystem II, and the recent determination of its structure has given strong hints of how nature uses solar energy to generate hydrogen and oxygen from water. This new information provides a blue print for scientists to seriously consider constructing catalysts that mimic the natural system and thus stimulate new technologies to address the energy/CO2 problem that humankind must solve. After all, there is no shortage of water for this non-polluting reaction and the energy content of sunlight falling on our planet well exceeds our needs. PMID- 17272239 TI - Carbon dioxide capture and geological storage. AB - Carbon dioxide capture and geological storage is a technology that could be used to reduce carbon dioxide emissions to the atmosphere from large industrial installations such as fossil fuel-fired power stations by 80-90%. It involves the capture of carbon dioxide at a large industrial plant, its transport to a geological storage site and its long-term isolation in a geological storage reservoir. The technology has aroused considerable interest because it can help reduce emissions from fossil fuels which are likely to remain the dominant source of primary energy for decades to come. The main issues for the technology are cost and its implications for financing new or retrofitted plants, and the security of underground storage. PMID- 17272240 TI - Good enough tools for global warming policy making. AB - We present a simple analysis of the global warming problem caused by the emissions of CO2 (a major greenhouse gas) into the atmosphere resulting from the burning of fossil fuels. We provide quantitative tools which enable policymakers and interested citizens to explore the following issues central to the global warming problem. (i) At what rate are we permitted to continue to emit CO2 after the global average atmospheric concentration has 'stabilized' at some chosen target level? The answer here provides the magnitude of the effort, measured by the necessary total reduction of today's global (annual) emissions rate to achieve stabilization. We shall see that stabilized emissions rates for all interesting stabilized concentration levels are much lower than the current emissions rate, but these small finite values are very important. (ii) Across how many years can we spread the total effort to reduce the annual CO2 emissions rate from its current high value to the above-mentioned low and stabilized target value? The answer here provides the time-scale of the total mitigation effort for any chosen atmospheric concentration target level. We confirm the common understanding that targets below a doubling of the pre-industrial concentration create great pressure to produce action immediately, while targets above double the pre-industrial level can tolerate longer periods of inaction. (iii) How much harder is the future mitigation effort, if we do not do our share of the job now? Is it a good idea to overshoot a stabilization target? The quantitative answers here provide the penalty of procrastination. For example, the mitigation task to avoid doubling the pre-industrial level is a problem that can be addressed gradually, over a period extending more than a century, if started immediately, but procrastination can turn the effort into a much more urgent task that extends over only a few decades. We also find that overshooting target levels is a bad idea. The quality of public discourse on this subject could be much enhanced if ball-park quantitative answers to these questions were more widely known. PMID- 17272241 TI - Pathways to hydrogen as an energy carrier. AB - When hydrogen is used as an alternative energy carrier, it is very important to understand the pathway from the primary energy source to the final use of the carrier. This involves, for example, the understanding of greenhouse gas emissions associated with the production of hydrogen and throughout the lifecycle of a given utilization pathway as well as various energy or exergy efficiencies and aspects involved. This paper which is based on a talk given at the Royal Society in London assesses and reviews the various production pathways for hydrogen with emphasis on emissions, energy use and energy efficiency. The paper also views some aspects of the breaking of the water molecule and examines some new emerging physical evidence which could pave the way to a new and more feasible pathway. A special attention will be given to the use of the renewable energy pathway. As an example of a hydrogen society that could be based on renewable primary energy, the paper describes the hydrogen society experiments in Iceland as well as unconventional hydrogen obtained from geothermal gases. In the light of our experience, attempts will be made to shed light upon drivers as well as obstacles in the development of a hydrogen society. PMID- 17272242 TI - Nuclear energy: current situation and prospects to 2020. AB - For close to half a century nuclear fission has been providing reliable supplies of electricity to the UK, with virtually no emissions of carbon dioxide. Over that period, the UK nuclear industry has avoided the emission of over one and a half billion tonnes of CO2. Yet no nuclear plant has been built in the UK for over two decades even though many of the stations in our current fleet are now within a decade or so of the end of their lifetime. Without new plants being ordered soon, the UK's nuclear capacity will decline dramatically, from 23% today to 3% post-2020--just as considerations of supply security and climate change are becoming increasingly important. Elsewhere in the world, many countries such as China, India, Japan, South Korea, Finland and France are building new stations. Other countries such as the USA, South Africa, and some nations that currently do not have nuclear stations (such as Indonesia and Poland) are making preparations for future nuclear stations. Globally capacity factors for nuclear plants are higher than they have ever been, averaging around 85% and with the best stations achieving well over 90%. Lifetime can be 60 years. That the economics of such stations compete well with other technologies is well founded and easily verifiable--especially in the face of rising fossil fuel prices and the pricing in of costs for CO2 emissions--both of which stand to improve the economics of nuclear energy still further. Waste volumes arising from modern plants are just a fraction of those of some earlier stations, and the technologies are in place to deal with them safely and effectively. Following recent reviews and international developments, there is growing confidence that internationally available competitive designs of nuclear plant will provide part of the solution to the UK's long-term energy needs. PMID- 17272245 TI - Wind energy. AB - From its rebirth in the early 1980s, the rate of development of wind energy has been dramatic. Today, other than hydropower, it is the most important of the renewable sources of power. The UK Government and the EU Commission have adopted targets for renewable energy generation of 10 and 12% of consumption, respectively. Much of this, by necessity, must be met by wind energy. The US Department of Energy has set a goal of 6% of electricity supply from wind energy by 2020. For this potential to be fully realized, several aspects, related to public acceptance, and technical issues, related to the expected increase in penetration on the electricity network and the current drive towards larger wind turbines, need to be resolved. Nevertheless, these challenges will be met and wind energy will, very likely, become increasingly important over the next two decades. An overview of the technology is presented. PMID- 17272244 TI - Marine energy. AB - Marine energy is renewable and carbon free and has the potential to make a significant contribution to energy supplies in the future. In the UK, tidal power barrages and wave energy could make the largest contribution, and tidal stream energy could make a smaller but still a useful contribution. This paper provides an overview of the current status and prospects for electrical generation from marine energy. It concludes that a realistic potential contribution to UK electricity supplies is approximately 80 TWh per year but that many years of development and investment will be required if this potential is to be realized. PMID- 17272246 TI - The path to fusion power. AB - Fusion is potentially an environmentally responsible and intrinsically safe source of essentially limitless power. It should be possible to build viable fusion power stations, and it looks as if the cost of fusion power will be reasonable. But time is needed to further develop the technology and to test in power station conditions the materials that would be used in their construction. Assuming no major adverse surprises, an orderly fusion development programme could lead to a prototype fusion power station putting electricity into the grid within 30 years, with commercial fusion power following some 10 or more years later. In the second half of the century, fusion could therefore be an important part of the portfolio of measures that are needed to cope with rising demand for energy in an environmentally responsible manner. In this paper, we describe the basics of fusion, its potential attractions, the status of fusion R&D, the remaining challenges and how they will be tackled at the International Tokamak Experimental Reactor and the proposed International Fusion Materials Irradiation Facility, and the timetable for the subsequent commercialization of fusion power. PMID- 17272247 TI - Another bleeding heart: perioperative heparin management revisited. PMID- 17272248 TI - Sample size calculations in randomized trials: common pitfalls. PMID- 17272249 TI - Preoperative low molecular weight heparin reduces heparin responsiveness during cardiac surgery. AB - PURPOSE: Cardiac surgery with cardiopulmonary bypass requires systemic anticoagulation, defined by an activated clotting time (ACT) of 400-480 sec. Patients with altered heparin responsiveness require disproportionately higher doses of heparin to achieve this target ACT. A common risk factor for heparin resistance is preoperative heparin therapy. Recently, therapy with low molecular weight heparin (LMWH) has become an acceptable substitute for prolonged heparin therapy. The current study examines the effect of preoperative LMWH therapy on subsequent heparin responsiveness during cardiac surgery. METHODS: Records of patients undergoing cardiac surgery with cardiopulmonary bypass over a period of four months were reviewed. We identified patients who, during the week preceding surgery, had received prolonged (>24 hr) therapy with either sc LMWH (LMWH group) or continuous iv unfractionated heparin (Heparin group). A Control group consisted of patients who received neither heparin nor LMWH preoperatively. The heparin sensitivity index (calculated as the first change in ACT from baseline divided by the first intraoperative heparin dose, normalized to body weight), was compared among groups using ANOVA. RESULTS: One hundred and thirty-nine patients were included in the analysis. The heparin sensitivity index was 33-45% higher in the Control group (1.6+/-0.7 sec.IU-1.kg-1; P<0.0001) compared to the LMWH (1.2+/ 0.4 sec.IU-1.kg-1) and Heparin (1.1+/-0.5 sec.IU-1.kg-1) groups. In a multivariable model, the use of preoperative LMWH remained a significant predictor of reduced intraoperative heparin responsiveness (P=0.002). CONCLUSION: Prolonged preoperative LMWH therapy, similar to the known effect of prolonged unfractionated heparin infusion, reduces subsequent intraoperative response to heparin. PMID- 17272250 TI - Protocol implementation in anesthesia: beta-blockade in non-cardiac surgery patients. AB - PURPOSE: An audit of intensive care unit (ICU) patients with perioperative myocardial ischemia and/or infarction (PMI/I) suggested under-use of prophylactic beta-adrenergic blocking drugs (ABDs). A multidisciplinary team developed an institutional protocol to identify at-risk patients, to standardize and facilitate prophylactic beta-adrenergic blockade, and to improve management of such patients. We report a retrospective assessment of the efficiency of program implementation. METHODS: Eligible preanesthesia assessment unit patients received metoprolol for one to four weeks prior to surgery, intraoperatively, and postoperatively. Patients with PMI/I requiring ICU admission were tracked from January 2002 to December 2004. The protocol was implemented in May 2003. The efficiency of program implementation was evaluated during two months of normal operating room activity (September 2003 and February 2004). RESULTS: The use of ABDs increased during the audit. Preoperative use increased from 31% in September 2003 to 39% of eligible patients in February 2004, with a stable surgical population. The incidence of patients with PMI/I admitted to ICU decreased from 2.6/1,000 surgical cases pre-implementation to 1.6/1,000 surgical cases post implementation (P=0.025). For the whole hospital, implementation was associated with a decrease in PMI/I incidence from 5.9 to 2.0/1,000 surgical cases (P<0.001). CONCLUSION: Heightened awareness and standardization of perioperative beta-blockade coincided with an increase in metoprolol use in at-risk patients and reduction in PMI/I. There was an increase in at-risk patients receiving prophylactic ABDs, a reduction in PMI/I diagnoses throughout the hospital, and reduced ICU patient admissions with PMI/I. PMID- 17272251 TI - Complications associated with the Esophageal-Tracheal Combitube in the pre hospital setting. AB - PURPOSE: The Esophageal-Tracheal Combitube (Combitube) is widely used for the management of the airway during cardiopulmonary resuscitation in the pre-hospital setting. Although serious complications have been reported with the Combitube, there is a paucity of data relative to the frequency and nature of such complications. The objective of this retrospective study was to determine the incidence and the nature of complications associated to the Combitube in the pre hospital setting. METHODS: Since 1993, in the Quebec City Health Region, the basic life support treatment algorithm for emergency medical technicians has included the use of a Combitube as the primary airway device for management of all patients presenting with cardiac or respiratory arrest. The database of the emergency coordination services was searched for the period between 1993 and 2003 (2,981 patients). Only those patients who survived at least 12 hr were included. Medical records of these patients were reviewed to identify complications related to the use of the Combitube. RESULTS: Two-hundred-eighty (280) patients were identified. Fifty-eight (58) patients (20.7%, confidence interval (CI)95%=16.0% 25.4%) presented 69 complications: aspiration pneumonitis (n=31), pulmonary aspiration (n=16), pneumothorax (n=6), upper airway bleeding (n=4), esophageal laceration (n=3), sc emphysema (n=2), esophageal perforation and mediastinitis (n=2), tongue edema (n=2), vocal cord injury (n=1), tracheal injury (n=1), and pneumomediastinum (n=1). Thirteen of these complications (12 patients, 4.3%, CI95%=2.0%-6.3%) were judged as most likely resulting from trauma associated with insertion of the Combitube. CONCLUSION: The use of the Combitube in the pre hospital setting is associated with a notable incidence of serious complications. PMID- 17272252 TI - The sniffing position provides greater occipito-atlanto-axial angulation than simple head extension: a radiological study. AB - PURPOSE: While the anatomic sniffing position has traditionally been considered the standard head and neck position for laryngoscopy, recent evidence suggests that the sniffing position provides no significant advantage over simple head extension. To establish if the sniffing position provides an anatomic advantage, we compared the occipito-atlanto-axial extension angle, a key determinant for obtaining a good laryngeal view during laryngoscopy, in simple head extension and sniffing positions. METHODS: Thirty volunteers with normal cervical spines were studied. Radiological examinations of the lateral cervical spine were taken and compared in each of the following three positions for each subject: neutral position (flat on the table with no pillow and without head extension or flexion); simple head extension (head maximally extended without a pillow); and the sniffing position (head extension with cervical flexion obtained by 7 cm occipital elevation). RESULTS: Mean angles of the occipito-atlanto-axial extension in simple head extension and the sniffing position were 20.4 degrees+/ 5.1 degrees and 24.2 degrees+/-5.6 degrees, respectively (P<0.01). CONCLUSION: The anatomic sniffing position provides greater occipito-atlanto-axial extension compared to simple head extension. These findings should be taken into consideration when optimizing patient positioning for laryngoscopy. PMID- 17272253 TI - A heated humidifier does not reduce laryngo- pharyngeal complaints after brief laryngeal mask anesthesia. AB - PURPOSE: Warming and humidification of inspired gases is standard care for intubated patients whose lungs are ventilated mechanically for prolonged periods. We examined whether active humidification of inspired gases might reduce laryngo pharyngeal discomfort in patients undergoing brief laryngeal mask airway (LMA) anesthesia. METHODS: In a prospective trial, 200 adult patients undergoing elective surgery under general anesthesia were randomly assigned to receive ventilation without airway warming and exogenous humidification (Group C control), or active warming and humidification of inspired gases (Group HUM humidified), using a humidifier with a heated wire circuit. Inhalational anesthesia was maintained via a circle system. The temperatures and relative humidities of inspired gases were monitored continuously throughout surgery. Postoperative sore throat, dysphonia, and dysphagia were assessed one and 24 hr after anesthesia. Whenever symptoms were present, their severities were graded using a 101-point numerical rating scale. RESULTS: The mean temperature and relative humidity of the inspired gases in Group HUM were greater compared to Group C (36.1+/-0.4 degrees C and 99.5+/-0.5% vs 26.9+/-0.8 degrees C and 76.4+/ 10.9%, respectively). Postoperatively, the overall frequencies of laryngeal and pharyngeal discomfort were similar in the two groups (53.8% and 54.9% in Group C vs 51.6% and 41.9% in Group HUM at one and 24 hr respectively, P>0.05). The groups were also similar with respect to the severity scores of laryngo pharyngeal discomfort. CONCLUSION: Active warming and humidification of inspired gases has no clinically appreciable effect in reducing the incidence and severity of laryngo-pharyngeal complaints after brief (5' DNA helicase activity, prefers forked substrate DNAs and anneals complementary DNAs. High-affinity DNA binding is ATP-dependent and low-affinity ATP-independent interactions contribute to forked substrate DNA binding and drive strand annealing. DmBLM combines DNA strand displacement with DNA strand annealing to catalyze the displacement of one DNA strand while annealing a second complementary DNA strand. PMID- 17272295 TI - Yeast Rrp14p is required for ribosomal subunit synthesis and for correct positioning of the mitotic spindle during mitosis. AB - Here we report that Rrp14p/Ykl082p is associated with pre-60S particles and to a lesser extent with earlier 90S pre-ribosomes. Depletion of Rrp14p inhibited pre rRNA synthesis on both the 40S and 60S synthesis pathways. Synthesis of the 20S precursor to the 18S rRNA was largely blocked, as was maturation of the 27SB pre rRNA to the 5.8S and 25S rRNAs. Unexpectedly, Rrp14p-depleted cells also showed apparently specific cell-cycle defects. Following release from synchronization in S phase, Rrp14p-depleted cells uniformly arrested in metaphase with short mitotic spindles that were frequently incorrectly aligned with the site of bud formation. In the absence of Bub2p, which is required for the spindle orientation checkpoint, this metaphase arrest was not seen in Rrp14p-depleted cells, which then arrested with multiple buds, several SPBs and binucleate mother cells. These data suggest that Rrp14p may play some role in cell polarity and/or spindle positioning, in addition to its function in ribosome synthesis. PMID- 17272296 TI - Exploiting noise in array CGH data to improve detection of DNA copy number change. AB - Developing effective methods for analyzing array-CGH data to detect chromosomal aberrations is very important for the diagnosis of pathogenesis of cancer and other diseases. Current analysis methods, being largely based on smoothing and/or segmentation, are not quite capable of detecting both the aberration regions and the boundary break points very accurately. Furthermore, when evaluating the accuracy of an algorithm for analyzing array-CGH data, it is commonly assumed that noise in the data follows normal distribution. A fundamental question is whether noise in array-CGH is indeed Gaussian, and if not, can one exploit the characteristics of noise to develop novel analysis methods that are capable of detecting accurately the aberration regions as well as the boundary break points simultaneously? By analyzing bacterial artificial chromosomes (BACs) arrays with an average 1 mb resolution, 19 k oligo arrays with the average probe spacing <100 kb and 385 k oligo arrays with the average probe spacing of about 6 kb, we show that when there are aberrations, noise in all three types of arrays is highly non Gaussian and possesses long-range spatial correlations, and that such noise leads to worse performance of existing methods for detecting aberrations in array-CGH than the Gaussian noise case. We further develop a novel method, which has optimally exploited the character of the noise, and is capable of identifying both aberration regions as well as the boundary break points very accurately. Finally, we propose a new concept, posteriori signal-to-noise ratio (p-SNR), to assign certain confidence level to an aberration region and boundaries detected. PMID- 17272297 TI - Release factors 2 from Escherichia coli and Thermus thermophilus: structural, spectroscopic and microcalorimetric studies. AB - Prokaryotic class I release factors (RFs) respond to mRNA stop codons and terminate protein synthesis. They interact with the ribosomal decoding site and the peptidyl-transferase centre bridging these 75 A distant ribosomal centres. For this an elongated RF conformation, with partially unfolded core domains II.III.IV is required, which contrasts the known compact RF crystal structures. The crystal structure of Thermus thermophilus RF2 was determined and compared with solution structure of T. thermophilus and Escherichia coli RF2 by microcalorimetry, circular dichroism spectroscopy and small angle X-ray scattering. The structure of T. thermophilus RF2 in solution at 20 degrees C is predominantly compact like the crystal structure. Thermodynamic analysis point to an initial melting of domain I, which is independent from the melting of the core. The core domains II.III.IV melt cooperatively at the respective physiological temperatures for T. thermophilus and E. coli. Thermodynamic analyses and the X-ray scattering results for T. thermophilus RF2 in solution suggest that the compact conformation of RF2 resembles a physiological state in absence of the ribosome. PMID- 17272298 TI - Arabidopsis thaliana telomeric DNA-binding protein 1 is required for telomere length homeostasis and its Myb-extension domain stabilizes plant telomeric DNA binding. AB - Telomeres are specific protein-DNA complexes that protect the ends of eukaryotic chromosomes from fusion and degradation and are maintained by a specialized mechanism exerted by telomerase and telomere-binding proteins (TBPs), which are evolutionarily conserved. AtTBP1 is an Arabidopsis thaliana protein that binds plant telomeric DNA in vitro. Here, we demonstrated that lack of AtTBP1 results in a deregulation of telomere length control, with mutant telomeres expanding steadily by the fourth generation. DNA-binding studies with mutant AtTBP1 proteins showed that the Myb-extension domain of AtTBP1 is required for binding to plant telomeric DNA. Our results suggest that AtTBP1 is involved in the telomere length mechanism in A. thaliana and that the Myb-extension domain of AtTBP1 may stabilize plant telomeric DNA binding. PMID- 17272299 TI - The gateway pDEST17 expression vector encodes a -1 ribosomal frameshifting sequence. AB - The attB1 site in the Gateway (Invitrogen) bacterial expression vector pDEST17, necessary for in vitro site-specific recombination, contains the sequence AAA AAA. The sequence A-AAA-AAG within the Escherichia coli dnaX gene is recognized as 'slippery' and promotes -1 translational frameshifting. We show here, by expressing in E. coli several plant cDNAs with and without single nucleotide deletions close to the translation initiation codons, that pDEST17 is intrinsically susceptible to -1 ribosomal frameshifting at the sequence C-AAA AAA. The deletion mutants produce correct-sized, active enzymes with a good correlation between enzyme amount and activity. We demonstrate unambiguously the frameshift through a combination of Edman degradation, MALDI-ToF mass fingerprint analysis of tryptic peptides and MALDI-ToF reflectron in-source decay (rISD) sequencing. The degree of frameshifting depends on the nature of the sequence being expressed and ranged from 25 to 60%. These findings suggest that caution should be exercised when employing pDEST17 for high-level protein expression and that the attB1 site has some potential as a tool for studying -1 frameshifting. PMID- 17272301 TI - Hearing loss, accidents, near misses and job losses in firefighters. AB - BACKGROUND: The hearing losses of workers exposed to occupational noise have been extensively documented, but no information exists on the level of hearing loss which results in job loss. AIM: To define levels of hearing loss associated with ill-health retirement (IHR), comparing them with existing standards and assessing the extent to which poor hearing contributes to accidents and near misses to assist the development of rational standards for retention. METHODS: All UK local authority fire brigades were approached for information on IHRs due to audiological problems, accident/near-miss totals and the numbers thought to be due to poor hearing in a 60-month period beginning in 1997. RESULTS: Only 15/59 (25%) of brigades provided all information requested, although 50 (85%) and 32 (52%) supplied medical and safety information, respectively, which was used for analysis. Of 3366 IHRs, 135 (4%) were due to audiological problems. When compared to a control group of firefighters of similar age, those taking IHR had worse mean and median hearing losses in all grouped frequencies in both ears than the controls, and this difference always reached statistical significance (P < 0.001), but there was considerable overlap in terms of range of hearing loss in each group. Only 41/31 274 (0.13%) of accidents/near misses reported were believed to result from hearing problems, and seven of these were related to device failure. CONCLUSIONS: Retention criteria based on audiometric grounds alone may result in unnecessary IHRs. Poor hearing is only responsible for a small proportion of accidents and near misses. PMID- 17272300 TI - Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes. AB - To investigate the feasibility of conducting a genomic-scale protein labeling and localization study in Escherichia coli, a representative subset of 23 coding DNA sequences (CDSs) was selected for chromosomal tagging with one or more fluorescent protein genes (EGFP, EYFP, mRFP1, DsRed2). We used lambda-Red recombination to precisely and efficiently position PCR-generated DNA targeting cassettes containing a fluorescent protein gene and an antibiotic resistance marker, at the C-termini of the CDSs of interest, creating in-frame fusions under the control of their native promoters. We incorporated cre/loxP and flpe/frt technology to enable multiple rounds of chromosomal tagging events to be performed sequentially with minimal disruption to the target locus, thus allowing sets of proteins to be co-localized within the cell. The visualization of labeled proteins in live E. coli cells using fluorescence microscopy revealed a striking variety of distributions including: membrane and nucleoid association, polar foci and diffuse cytoplasmic localization. Fifty of the fifty-two independent targeting experiments performed were successful, and 21 of the 23 selected CDSs could be fluorescently visualized. Our results show that E. coli has an organized and dynamic proteome, and demonstrate that this approach is applicable for tagging and (co-) localizing CDSs on a genome-wide scale. PMID- 17272302 TI - Are hip protectors correctly positioned in use? AB - There are many designs of hip protectors ranging from small elliptical shaped hard shell designs to large circular soft pads. They are held in position usually by being contained in a close fitting pocket on a garment that patients wear all the time they are at risk of sustaining a fracture of the hip if they fall onto the area of the greater trochanter (GT). It is important for the function of the hip protector that the pad element is positioned over the GT when the subject falls onto a surface such as the floor so as to provide the maximal protection by reducing the large forces transmitted to the femoral neck that lead to the fracture of the bone. In this study, anatomical measurements show where the GT is relevant to the centre of the hip protector, and position and movement studies have shown that generally the hard shell design of the hip protector lies posterior and proximal to the GT both for erect and flexed positions of the hip. The position of the GT relevant to the anterior superior iliac crest was established using ultrasound examinations on control and patients admitted with a fracture of the hip due to a fall. The diagonal surface distance for the three groups of test subjects was approximately 12 cm and a template was developed that could be used to locate the GT. A 'zone' of GT position and movement has been established relative to the anterior superior iliac crest, and designers of garments should ensure that this zone is within the area of protection provided by their hip protector pad design. PMID- 17272303 TI - An anatomical assessment of branch abscission and branch-base hydraulic architecture in the endangered Wollemia nobilis. AB - BACKGROUND AND AIMS: The branch-base xylem structure of the endangered Wollemia nobilis was anatomically investigated. Wollemia nobilis is probably the only extant tree species that produces only first-order branches and where all branches are cleanly abscised. An investigation was carried out to see if these unusual features might influence branch-base xylem structure and water supply to the foliage. METHODS: The xylem was sectioned at various distances along the branch bases of 6-year-old saplings. Huber values and relative theoretical hydraulic conductivities were calculated for various regions of the branch base. KEY RESULTS: The most proximal branch base featured a pronounced xylem constriction. The constriction had only 14-31 % (average 21 %) of the cross sectional area and 20-42 % (average 28 %) of the theoretical hydraulic conductivity of the more distal branch xylem. Wollemia nobilis had extremely low Huber values for a conifer. CONCLUSIONS: The branch-base xylem constriction would appear to facilitate branch abscission, while the associated Huber values show that W. nobilis supplies a relatively large leaf area through a relatively small diameter 'pipe'. It is tempting to suggest that the pronounced decline of W. nobilis in the Tertiary is related to its unusual branch-base structure but physiological studies of whole plant conductance are still needed. PMID- 17272304 TI - Nuclear DNA content estimates in green algal lineages: chlorophyta and streptophyta. AB - BACKGROUND AND AIMS: Consensus higher-level molecular phylogenies present a compelling case that an ancient divergence separates eukaryotic green algae into two major monophyletic lineages, Chlorophyta and Streptophyta, and a residuum of green algae, which have been referred to prasinophytes or micromonadophytes. Nuclear DNA content estimates have been published for less than 1% of the described green algal members of Chlorophyta, which includes multicellular green marine algae and freshwater flagellates (e.g. Chlamydomonas and Volvox). The present investigation summarizes the state of our knowledge and adds substantially to our database of C-values, especially for the streptophyte charophycean lineage which is the sister group of the land plants. A recent list of 2C nuclear DNA contents for isolates and species of green algae is expanded by 72 to 157. METHODS: The DNA-localizing fluorochrome DAPI (4',6-diamidino-2 phenylindole) and red blood cell (chicken erythrocytes) standard were used to estimate 2C values with static microspectrophotometry. KEY RESULTS: In Chlorophyta, including Chlorophyceae, Prasinophyceae, Trebouxiophyceae and Ulvophyceae, 2C DNA estimates range from 0.01 to 5.8 pg. Nuclear DNA content variation trends are noted and discussed for specific problematic taxon pairs, including Ulotrichales-Ulvales, and Cladophorales-Siphonocladales. For Streptophyta, 2C nuclear DNA contents range from 0.2 to 6.4 pg, excluding the highly polyploid Charales and Desmidiales, which have genome sizes of up to 14.8 and 46.8 pg, respectively. Nuclear DNA content data for Streptophyta superimposed on a contemporary molecular phylogeny indicate that early diverging lineages, including some members of Chlorokybales, Coleochaetales and Klebsormidiales, have genomes as small as 0.1-0.5 pg. It is proposed that the streptophyte ancestral nuclear genome common to both the charophyte and the embryophyte lineages can be characterized as 1C = 0.2 pg and 1n = 6. CONCLUSIONS: These data will help pre screen candidate species for the on-going construction of bacterial artificial chromosome nuclear genome libraries for land plant ancestors. Data for the prasinophyte Mesostigma are of particular interest as this alga reportedly most closely resembles the 'ancestral green flagellate'. Both mechanistic and ecological processes are discussed that could have produced the observed C-value increase of >100-fold in the charophyte green algae whereas the ancestral genome was conserved in the embryophytes. PMID- 17272306 TI - BMP4 induces EMT and Rho GTPase activation in human ovarian cancer cells. AB - We identified previously an autocrine bone morphogenetic protein-4 (BMP4) signalling pathway in primary human normal ovarian surface epithelial (OSE) and epithelial ovarian cancer (OvCa) cells. Herein we show that treatment of OvCa cells with BMP4 produced morphological alterations and increased cellular adhesion, motility and invasion. The BMP4 inhibitor noggin blocked the BMP4 induced phenotype, and decreased autocrine BMP4-mediated OvCa cell motility and adherence. In response to exogenous BMP4, the epithelial-mesenchymal transition (EMT) markers Snail and Slug mRNA and protein were up-regulated, E-cadherin mRNA and protein were down-regulated and the network of alpha smooth muscle actin changed to resemble a mesenchymal cell. We also observed changes in the level of activated Rho GTPases in OvCa cells treated with BMP4, strongly suggesting that the changes in morphology, adhesion, motility and invasion are probably mediated through the activation of these molecules. Strikingly, treatment of normal OSE cells with BMP4 or noggin failed to alter cell motility, providing evidence that OSE and OvCa cells possess a distinct capability to respond to BMP4. Overall, our studies suggest a link between autocrine BMP signalling mediated through the Rho GTPase family and Snail- and Slug-induced EMT that may collectively contribute to aggressive OvCa behaviour. PMID- 17272305 TI - A wheat (Triticum aestivum) protein phosphatase 2A catalytic subunit gene provides enhanced drought tolerance in tobacco. AB - BACKGROUND AND AIMS: Multiple copies of genes encoding the catalytic subunit (c) of protein phosphatase 2A (PP2A) are commonly found in plants. For some of these genes, expression is up-regulated under water stress. The aim of this study was to investigate expression and characterization of TaPP2Ac-1 from Triticum aestivum, and to evaluate the effects of TaPP2Ac-1 on Nicotiana benthamiana in response to water stress. METHODS: TaPP2Ac-1 cDNA was isolated from wheat by in silico identification and RT-PCR amplification. Transcript levels of TaPP2Ac-1 were examined in wheat responding to water deficit. Copy numbers of TaPP2Ac-1 in wheat genomes and subcellular localization in onion epidermal cells were studied. Enzyme properties of the recombinant TaPP2Ac-1 protein were determined. In addition, studies were carried out in tobacco plants with pCAPE2-TaPP2Ac-1 under water-deficit conditions. KEY RESULTS: TaPP2Ac-1 cDNA was cloned from wheat. Transcript levels of TaPP2Ac-1 in wheat seedlings were up-regulated under drought condition. One copy for this TaPP2Ac-1 was present in each of the three wheat genomes. TaPP2Ac-1 fused with GFP was located in the nucleus and cytoplasm of onion epidermis cells. The recombinant TaPP2Ac-1 gene was over-expressed in Escherichia coli and encoded a functional serine/threonine phosphatase. Transgenic tobacco plants over-expressing TaPP2Ac-1 exhibited stronger drought tolerance than non-transgenic tobacco plants. CONCLUSIONS: Tobacco plants with pCAPE2-TaPP2Ac-1 appeared to be resistant to water deficit, as shown by their higher capacity to maintain leaf relative water content, leaf cell-membrane stability index, water-retention ability and water use efficiency under water stress. The results suggest that the physiological role of TaPP2Ac-1 is related to drought stress response, possibly through its involvement in drought responding signal transduction pathways. PMID- 17272307 TI - Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities. AB - Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents' lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2(+/-)) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2(+/-) mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2(+/-) mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15(Ink4b), p16(Ink4a) and p19(Arf) or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2(+/-) mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation. PMID- 17272309 TI - CpG island promoter hypermethylation of the pro-apoptotic gene caspase-8 is a common hallmark of relapsed glioblastoma multiforme. AB - Glioblastoma multiforme (GBM) is an incurable malignancy with inherent tendency to recur. In this study, we have comparatively analyzed the epigenetic profile of 32 paired tumor samples of relapsed GBM and their corresponding primary neoplasms with special attention to genes involved in the mitochondria-independent apoptotic pathway. The CpG island promoter hypermethylation status was assessed by methylation-specific polymerase chain reaction and selected samples were double checked by bisulfite genomic sequencing. Thirteen genes were analyzed for DNA methylation: the pro-apoptotic CASP8, CASP3, CASP9, DcR1, DR4, DR5 and TMS1; the cell adherence CDH1 and CDH13; the candidate tumor suppressor RASSF1A and BLU; the cell cycle regulator CHFR and the DNA repair MGMT. The CpG island promoter hypermethylation profile of relapsed GBM in comparison with their corresponding primary tumors was identical in 37.5% of the cases, whereas in 62.5% of patients, differences in the DNA methylation patterns of the 13 genes were observed. The most prominent distinction was the presence of previously undetected CASP8 hypermethylation in the GBM relapses (P = 0.031). This finding was also linked to the observation that an unmethylated CASP8 CpG island together with methylated BLU promoter in the primary GBM was associated with prolonged time to tumor progression (P = 0.0035). Our data strongly suggest that hypermethylation of the pro-apoptotic CASP8 is a differential feature of GBM relapses. These remarkable findings may foster the development of therapeutic approaches using DNA demethylating drugs and activators of the extrinsic apoptotic pathway to improve the dismal prognosis of GBM. PMID- 17272308 TI - Gene expression analysis during tumor enhancement by the dietary phytochemical, 3,3'-diindolylmethane, in rainbow trout. AB - Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM), a primary I3C derivative, are known dietary chemopreventive agents also available as supplements. However, I3C has been found to act as a tumor promoter in rat (multi organ) and trout (liver) models. I3C and DIM were previously found to be estrogenic in trout liver based on toxicogenomic profiles. In this study, we compare the post-initiation effects of DIM and 17beta-estradiol (E2) on aflatoxin B(1) (AFB(1))-induced hepatocarcinogenesis in trout. Trout were initiated as embryos with AFB(1) and juvenile fish were fed diets containing 0, 120 or 400 p.p.m. DIM or 5 p.p.m. E2 for 18 weeks. Tumor incidence was determined at 13 months and found to be significantly elevated in AFB(1)-initiated trout fed either 400 p.p.m. DIM or 5 p.p.m. E2 compared with control animals. To evaluate the mechanism of tumor enhancement, hepatic gene expression profiles were examined in animals fed promotional diets during the course of tumorigenesis and in hepatocellular carcinomas (HCCs) of initiated animals. We demonstrate that DIM alters gene expression profiles similar to E2 in liver samples during tumorigenesis and in HCC tumors. Further, HCCs from animals on DIM and E2 promotional diets had a transcriptional signature indicating decreased invasive or metastatic potential compared with HCCs from control animals. Overall, these findings are the first to demonstrate tumor promotion by DIM. They confirm the importance of estrogenic signaling in the mechanism of promotion by dietary indoles in trout liver and indicate a possible dual effect that enhances tumor incidence and decreases potential for metastasis. PMID- 17272312 TI - Lingual amyloidosis--a rare complication of long-term haemodialysis. PMID- 17272311 TI - Influence of moderate dehydration on soccer performance: physiological responses to 45 min of outdoor match-play and the immediate subsequent performance of sport specific and mental concentration tests. AB - OBJECTIVE: To determine whether moderate water loss (approximately 1.5-2% of body mass (BM)) represents a significant impairment to soccer match-play and the related fitness variables. METHODS: 11 moderately active male soccer players (mean (SD) age 24.4 (3) years, BM 74.03 (10.5) kg, peak oxygen consumption 50.91 (4.0) ml/kg/min) volunteered to participate. The experimental procedure comprised: (1) a 45 min pre-match period of cycle ergometry exercise (90% of individual ventilatory threshold); (2) the completion of a 45 min soccer match; and (3) the immediate post-match performance of sport-specific and mental concentration tests. The subjects completed the procedure on three occasions each in a different experimental condition (fluid intake (FL), no fluid (NF) and mouth rinse (MR)) in an individually randomised order. Core temperature (Tc), heart rates, plasma and urine osmolalities, BM, sweat rates and heat storage were all measured. RESULTS: The only condition-dependent difference during the match-play element of the protocol was a significantly increased Tc in the NF condition compared with the FL condition (39.28 degrees C (0.35 degrees C) and 38.8 degrees C (0.47 degrees C), respectively; p<0.05). The immediate post-match performance of a sport-specific fitness test was significantly impaired where FL had been denied (p<0.01). The post-test evaluation of rating of perceived exertion and thirst indicated that the NF condition was perceived to be the most challenging (p<0.05). CONCLUSIONS: The condition-dependent differences in match-play and post match tests demonstrate that moderate dehydration is detrimental to soccer performance. However, it remains unclear whether this could be attributable to water loss in itself or the negative psychological associations derived from a greater perception of effort in that condition. PMID- 17272310 TI - Increase of carcinogenic risk via enhancement of cyclooxygenase-2 expression and hydroxyestradiol accumulation in human lung cells as a result of interaction between BaP and 17-beta estradiol. AB - Animal studies demonstrated that females are more susceptible than males to benzo[a]pyrene (BaP)-induced toxicities, including lung carcinogenesis. Elevation of cyclooxygenase-2 (COX-2) expression has been shown to increase the risk of cancer development. BaP induces COX-2 expression, and an interaction between BaP and estrogen in relation to COX-2 expression is suspected. In the present study, 10 muM BaP alone only slightly increased COX-2 mRNA expression and 10 nM 17-beta estradiol (E(2)) alone slightly increased prostaglandin E2 (PGE2) secretion in human bronchial epithelial cells. However, co-treatment with BaP and E(2) potentiated COX-2 mRNA expression and significantly elevated PGE2 secretion. Utilizing specific inhibitors and reporter assays, we further investigated the potentiation mechanisms of E(2) on BaP-induced COX-2 expression. First, E(2) activated estrogen receptor to increase PGE2 secretion, which directly increased COX-2 expression. Second, E(2) potentiated BaP-induced nuclear factor-kappaB (NF kappaB) activation, which regulates COX-2 expression. Third, although the aryl hydrocarbon receptor (AhR) did not play a role in BaP-induced COX-2 expression, the potentiation effect of E(2) itself was AhR dependent. We further demonstrated that BaP induced the production of genotoxic E(2) metabolites (2- and 4 hydroxyestradiols) via AhR-up-regulated cytochromes P450 1A1 and 1B1. These metabolites could directly activate NF-kappaB to further promote COX-2 mRNA expression in human lung epithelial cells. These findings were further supported by increased PGE2 secretion in rat lung slice cultures. Our findings that the BaP E(2) interaction enhanced COX-2 expression and hydroxyestradiol accumulation in the media of cultivated lung cells and tissues provide the needed scientific basis for higher risk of BaP-associated lung cancer in females. PMID- 17272313 TI - Association between the metabolic syndrome and chronic kidney disease in Chinese adults. AB - BACKGROUND: The metabolic syndrome is a common risk factor for cardiovascular and chronic kidney disease (CKD) in Western populations. We examined the relationship between the metabolic syndrome and risk of CKD in Chinese adults. METHODS: A cross-sectional survey was conducted in a nationally representative sample of 15 160 Chinese adults aged 35-74 years. The metabolic syndrome was defined as the presence of three or more of the following risk factors: elevated blood pressure, low high density lipoprotein (HDL)-cholesterol, high triglycerides, elevated plasma glucose and abdominal obesity. CKD was defined as an estimated glomerular filtration rate<60 ml/min/1.73 m2 and elevated serum creatinine was defined as >or=1.14 mg/dl in men and >or=0.97 mg/dl in women (>or=95th percentile of serum creatinine in Chinese men and women aged 35-44 years without hypertension or diabetes, respectively). RESULTS: The multivariate-adjusted odds ratios [95% confidence interval (CI)] of CKD and elevated serum creatinine in participants with compared to those without the metabolic syndrome were 1.64 (1.16, 2.32) and 1.36 (1.07, 1.73), respectively. Compared to participants without any components of the metabolic syndrome, the multivariate-adjusted odds ratios (95% CI) of CKD were 1.51 (1.02, 2.23), 1.50 (0.97, 2.32), 2.13 (1.30, 3.50) and 2.72 (1.50, 4.93) for those with 1, 2, 3, and 4 or 5 components, respectively. The corresponding multivariate-adjusted odds ratios (95% CI) of elevated serum creatinine were 1.11 (0.88, 1.40), 1.39 (1.07, 2.04), 1.47 (1.06, 2.04) and 2.00 (1.32, 3.03), respectively. CONCLUSIONS: These findings suggest that the metabolic syndrome might be an important risk factor for CKD in Chinese adults. PMID- 17272315 TI - Physiology, propaganda, and pound animals: medical research and animal welfare in mid-twentieth century America. AB - In 1952, the University of Michigan physiologist Robert Gesell shocked his colleagues at the business meeting of the American Physiological Society by reading a prepared statement in which he claimed that some of the animal experimentation being carried out by scientists was inhumane. He especially attacked the National Society for Medical Research (NSMR), an organization that had been founded to defend animal experimentation. This incident was part of a broader struggle taking place at the time between scientists and animal welfare advocates with respect to what restrictions, if any, should be placed on animal research. A particularly controversial issue was whether or not pound animals should be made available to laboratories for research. Two of the prominent players in this controversy were the NSMR and the Animal Welfare Institute, founded and run by Gesell's daughter, Christine Stevens. This article focuses on the interaction between these two organizations within the broader context of the debate over animal experimentation in the mid-twentieth century. PMID- 17272314 TI - Glucose-added dialysis fluid prevents asymptomatic hypoglycaemia in regular haemodialysis. AB - BACKGROUND: Hypoglycaemia (HG) has been demonstrated during chronic haemodialysis (HD). These events may become more frequent with the current use of glucose-free bicarbonate dialysis solution, the standard formula in most dialysis facilities in the last decade. On the other hand, HG-related symptoms are unusual among patients during or just after dialysis sessions. The aim of this study was to evaluate the occurrence of HG in diabetic (DM) and non-diabetic (NDM) end-stage renal failure patients during HD using dialytic solution without and with glucose. METHODS: Forty-two chronic renal failure patients-21 DM and 21 NDM randomly selected among the 97 in our dialysis unit were submitted to an HD session with glucose-free bicarbonate solution (phase 1). Serum glucose was measured at 30, 60, 150 and 240 min. In eight patients (four DM and four NDM) glucose was also measured in fluid leaving the dialyser at 30, 60 and 150 min. After a week, all procedures were repeated in the same patients, this time with a 90 mg/dl glucose-added bicarbonate solution (phase 2). We compared the glucose levels and the number of symptomatic and asymptomatic HG events in each group in phases 1 and 2, using bivariate analysis methods with confidence limit of 0.95%. RESULTS: Data were expressed as mean+/-SD. No patient presented any clinical evidence of HG. For all patients, the mean plasma glucose level (mg/dl) was significantly higher in phase 2 than in phase 1 (138.2+/-96.3 vs 120.7+/-75.9; P=0.0392). This occurred in DM (171.1+/-104.5 vs 132.5+/-71.0; P=0.0067), but not in NDM (101.3+/-19.4 vs 95.2+/-21.2; P=0.06). With glucose-free HD solution, 10 patients (five DM, five NDM) presented 18 measures of glycaemia under 70 mg/dl, and with glucose-added solution, only one (DM) presented two measures under 70 mg/dl-P=0.0045 (number of patients); P=0.0003 (number of HG measures). Among DM patients, values for HG measures in phase 1 (49.1+/-16.2 mg/dl) were significantly lower than in phase 2 (65.0+/-1.4 mg/dl)-P=0.0139. For all patients, glucose was lost in HD fluid leaving the dialyser at lower values in phase 2 (5.2+/-2.9 g/h) than in phase 1 (16.7+/-10.9 g/h)-P<0.0001. CONCLUSIONS: Asymptomatic HG was frequent during HD when glucose-free dialysis solution was used. Glucose was lost in dialytic fluid leaving the dialyser in significantly lower amounts when using glucose-added solution than glucose-free solution. Glucose-added dialysis solution at 90 mg/dl significantly reduced the number and severity of HG episodes and although it caused higher mean glycaemia in DM patients during HD, its use seems advisable in all patients. PMID- 17272316 TI - The role of the outpatient clinic in chemotherapy for patients with unresectable or recurrent gastric cancer. AB - BACKGROUND: Recently, outpatient chemotherapy centers have become popular in Japan. To clarify the actual conditions of outpatient clinics, we surveyed entire clinical courses of chemotherapy in patients with unresectable or recurrent gastric cancer. METHODS: From the medical records of 64 patients with unresectable or recurrent gastric cancer with no prior chemotherapy, we obtained data on overall survival, non-hospitalized survival, the number of and reasons for attendance at the outpatient clinic and hospitalization, and medical conditions at discharge. RESULTS: The median follow-up time was 520 days, the median survival time was 353 days, and the median non-hospitalized survival time was 282 days. Patients attended the outpatient clinic 1917 times in total; 145 (8%) of these were unplanned visits for accidental disease, disease progression, or toxicity. Patients were hospitalized 291 times in total: 110 (38%) of hospitalizations were unplanned or emergencies because of disease progression or toxicity. Patients were discharged 290 times in total; in 56 of these discharges (19%) unresolved medical problems remained, such as toxicity, total parenteral nutrition, or symptoms related to cancer. Three patients (5%) died from treatment related leucopenia and thrombocytopenia. CONCLUSIONS: Patients with unresectable and recurrent gastric cancer were treated at outpatient clinics for periods up to 80% longer than the entire clinical course of chemotherapy. However, there were some unplanned or emergency hospitalizations and some patients still experienced medical problems at discharge. The role of the outpatient clinic is very important to chemotherapy for patients with unresectable or recurrent gastric cancer. PMID- 17272317 TI - Prognostic factors in patients with gemcitabine-refractory pancreatic cancer. AB - OBJECTIVE: The purpose of this study was to identify prognostic factors in patients with gemcitabine-refractory pancreatic cancer and to determine criteria for selecting candidates for second-line treatment. METHODS: The records of 74 patients who were treated with gemcitabine (GEM) and followed up until disease progression were reviewed retrospectively. Sixteen clinical variables at the time of disease progression after GEM chemotherapy were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULTS: At the time of analysis, 71 patients had died because of tumor progression. The overall median survival time was 5.1 months after first-line chemotherapy with GEM was initiated. Median survival time after disease progression was 2.0 months. Three factors, performance status, peritoneal dissemination and C-reactive protein level, were identified as independent prognostic factors in multivariate analysis. Median survival time in the good prognosis group (patients with performance status 0 or 1, no peritoneal dissemination and C-reactive protein <5.0 mg/dl) was 3.4 months. CONCLUSIONS: Performance status, serum level of C-reactive protein and peritoneal dissemination were identified as important prognostic factors in patients with GEM-refractory pancreatic cancer. These factors should be considered in determining the treatment following first-line chemotherapy in patients with advanced pancreatic cancer. PMID- 17272318 TI - A mathematical estimation of true cancer incidence using data from population based cancer registries. AB - BACKGROUND: Accurate cancer incidence data are needed to plan, monitor and evaluate national cancer control programs. In Japan, however, such information is not available owing to incomplete cancer registries. In order to attain incidence estimation adjusted to account for this incomplete information, we have developed a new method. METHODS: We developed a nonlinear regression model between observed incidence/mortality ratios and proportions of death certificate notification to observed incidence in various cancer registries. This model enables us to obtain the 'true incidence/mortality ratio', which, in the regression curve, is at zero point for the proportion of death certificate notifications. This is an ideal registration state without any missing cases. By multiplying it by the number of cancer mortalities from the National Vital Statistics, corrected cancer incidence can be estimated. RESULTS: Applying this method for the estimation of the Japanese cancer incidence in 1997, we obtained the 'true incidence/mortality ratios' of 2.074 for men and 2.587 for women. Cancer incidences in Japan for 1997 were thus estimated to be 346,000 for men and 280,000 for women. CONCLUSIONS: A new method is proposed to estimate the national cancer incidence after adjusting for completeness of cancer registries. This method enables us to more accurately estimate the cancer incidence in a country where several cancer registries exist with various degrees of completeness of registration. PMID- 17272319 TI - Diagnosis and treatment of Ewing's sarcoma. AB - Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of Ewing's sarcomas, primitive neuroectodermal tumors and Askin's tumors. Therefore, these lesions have become regarded as a single entity, dubbed the Ewing's family of tumors. RT-PCR to detect EWS-ETS gene arrangements is widely used to confirm the diagnosis of Ewing's family of tumors. Experimental results suggest that inhibition of the signaling pathway downstream of the EWS ETS gene may lead to the development of molecularly targeted therapy in the future. PMID- 17272320 TI - Surgical results of lung cancer with sarcoid reaction in regional lymph nodes. AB - BACKGROUND: There have been few reports of sarcoid reaction in the regional lymph nodes associated with lung cancer. The purpose of this study was to analyze the surgical results of lung cancer with sarcoid reaction. METHODS: Of 1733 lung cancer patients undergoing surgical treatment in our institute from 1990 to 2004, we reviewed 22 patients (1.3%) with sarcoid reaction in the regional lymph nodes of lung cancer. RESULTS: On pre-operative computed tomography (CT), mediastinal lymph node swelling was detected in 19 patients (86%) as clinical N3 disease (c N3) in six or as c-N2 in 13, while three patients were classified as c-N0. To these 19 patients, lymph node status was histologically checked by mediastinoscopy in four patients, sternotomy approach in two and open mini thoracotomy in 13. Because the sampling-biopsy nodes showed no tumor metastasis, radical surgery was promptly performed. However, four patients (18%) were finally judged to have pathological lymph node positive disease. Five patients were in pathological stage (p-stage) IA, nine in p-stage IB, five in p-stage IIB, two in p-stage IIIA, and one in stage IIIB. The overall 3-, and 5-year survival rates of these patients were 85.2 and 77.7%, respectively, with no significant difference compared to those of the remaining patients without sarcoid reaction. CONCLUSIONS: Because lung cancer patients with sarcoid reaction in the regional lymph nodes frequently show mediastinal lymph node swelling on CT, radical resection should be performed after confirming the node status by appropriate sampling biopsy. It seems that surgical results of lung cancers with sarcoid reaction in the regional nodes are not prognostically different from those without sarcoid reaction. PMID- 17272322 TI - Struma ovarii associated with Meigs syndrome. PMID- 17272321 TI - Combination chemotherapy with capecitabine (X) and Cisplatin (P) as first line treatment in advanced gastric cancer: experience of 223 patients with prognostic factor analysis. AB - BACKGROUND: The efficacy and safety of the combination of capecitabine (X) and cisplatin (P) in the treatment of advanced gastric cancer (AGC) have already been shown in several prospective clinical trials. In this study, we sought to evaluate the efficacy and feasibility of the XP combination for the treatment of AGC in clinical practice and to determine the prognostic factors affecting treatment outcomes. METHODS: Clinical data from 223 patients with previously untreated metastatic, unresectable, or recurrent gastric carcinoma who were treated with XP between March 2000 and December 2004 at a single center were reviewed. Each 3-week chemotherapy cycle consisted of oral capecitabine (1000 1250 mg/m2 twice a day on days 1-14) and i.v. cisplatin (60-80 mg/m2 on day 1). RESULTS: Of the 223 patients, 32 had distant metastases but palliative gastrectomy (resected metastatic), 82 had recurrent disease after previous curative gastrectomy (recurrent), and 109 had distant metastases without gastrectomy (initially metastatic). Patients received a median of five cycles of chemotherapy (range, 1-12 cycles). Among the 123 patients with measurable disease, seven achieved complete responses and 49 had partial responses, giving an overall response rate (RR) of 45.5% in the intention-to-treat population (95% CI, 32.9-50.2%). There were no differences in RR among the groups of resected metastatic, recurrent and initially metastatic patients (66.7 versus 36.5 versus 50.8%, P = 0.35). After a median follow-up of 11.9 months (range, 2.1-51.9 months), the median time to progression (TTP) was 6.3 months (95% CI, 5.2-7.4 months) and the median overall survival (OS) was 11.1 months (95% CI, 9.4-12.9 months). In the resected metastatic, recurrent and initially metastatic groups, TTP was 8.7, 6.8 and 5.8 months (P = 0.02) and median OS was 14.7, 12.4 and 9.6 months (P = 0.03), respectively. Multivariate analysis showed that relatively small tumor burden (resected metastatic or recurrent versus initially metastatic groups) (OR = 1.418, 95% CI, 1.021-1.967, P = 0.037) and good performance status (ECOG 0-1 versus 2) (OR = 3.800, 95% CI, 2.417-5.974, P < 0.001) were independent prognostic factors affecting overall survival. CONCLUSION: The combination of capecitabine and cisplatin was active and well tolerated as a first line treatment of AGC in general clinical practice. Disease status and performance status of the patients were the most important factors in treatment outcomes. PMID- 17272323 TI - International comparisons of cumulative risk of gallbladder cancer and other biliary tract cancer, from Cancer Incidence in Five Continents Vol. VIII. PMID- 17272325 TI - Sudden cardiac death in Andersen-Tawil syndrome. AB - Andersen-Tawil syndrome (ATS) is an autosomal dominant or sporadic disorder characterized by periodic paralysis, dysmorphic features, and ventricular arrhythmias. Although ventricular tachycardia burden is quite high sudden cardiac death in ATS is rare. We describe a case with sudden cardiac death due to electrical storm a few days after ICD implantation in KCNJ2 mutation-negative ATS. PMID- 17272326 TI - Single-chamber ventricular pacing increases markers of left ventricular dysfunction compared with dual-chamber pacing. AB - AIMS: Large randomized trials comparing DDD with VVI pacing have shown no differences in mortality, but conflicting evidence exists in regard to heart failure endpoints. Here we evaluated the effect of pacing mode on serum levels of brain natriuretic peptide (BNP) and amino-terminal-proBNP (NT-proBNP). Methods Forty-one patients (age 73 +/- 10 years) with dual-chamber pacemakers were included in a prospective, single-blind, randomized crossover study evaluating the impact of DDD(R)/VDD versus VVI(R) mode on objective and functional parameters. Data were collected after a 2-week run-in phase and after 2 weeks each of VVI(R) and DDD(R)/VDD pacing or vice versa. Results BNP and NT-proBNP levels during DDD(R)/VDD stimulation (151 +/- 131 and 547 +/- 598 pg/mL) showed no change compared with baseline (154 +/- 130 and 565 +/- 555 pg/mL), but a significant 2.4-fold increase was observed during VVI(R) mode [360 +/- 221 and 1298 +/- 1032 pg/mL; P < 0.001 compared with DDD(R)/VDD]. The assessment of functional class, the presence of pacemaker syndrome [49% in VVI(R) mode] and the patients' preferred pacing mode showed significant differences in favour of DDD(R)/VDD pacing. CONCLUSION: Patients can differentiate between DDD(R)/VDD and VVI(R) pacing, and prefer the former. Compared with DDD(R)/VDD pacing, VVI(R) stimulation induces a two- to three-fold increase in serum BNP and NT-proBNP levels. PMID- 17272327 TI - Electrophysiological effects of intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells. AB - AIMS: Autologous stem cell transplantation has been successfully used for repair of infarcted myocardium, but concerns have been raised regarding its pro arrhythmic potential. This study aimed at using electrophysiological assessment, and the monitoring and data storage capacity of implanted cardioverter defibrillators (ICDs), in order to evaluate the possible proarrhythmic potential of stem cell transplantation. METHODS: Five patients with a history of previous anteroseptal myocardial infarction and an implanted ICD for ventricular arrhythmias underwent intracoronary transplantation of autologous bone marrow derived and culture-expanded mesenchymal stem cells in combination with endothelial progenitors. RESULTS: There was evidence of myocardial repair in three patients in whom segmental left ventricular wall motion improvement was detected on stress echocardiography. Before stem cell transplantation, clinical non-sustained ventricular tachycardia and inducible monomorphic ventricular tachycardia, or ventricular flutter at electrophysiology study were demonstrated in all patients. At 16-36 months follow-up, interrogation of the ICD failed to detect sustained or non-sustained ventricular arrhythmia in any patient. At repeat electrophysiology study, sustained ventricular arrhythmia was induced in two patients. CONCLUSION: Intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells does not appear to be arrhythmogenic in humans. Further studies are needed on this important clinical issue. PMID- 17272328 TI - Is vasovagal syncope a disease? AB - Vavovagal syncope (VVS) is not generally associated with cardiovascular, neurological or other diseases, and, therefore, represents an isolated manifestation. Isolated VVS cannot be regarded as a disease for several reasons: spontaneous syncope occurs in about half of individuals during their lives, and the unidentified neural pathways involved in the vasovagal response are probably present in all healthy humans, with individual differences in susceptibility; VVS is induced during tilt testing in several subjects with no history of syncope; during haemorrhagic shock, the vasovagal reaction can be observed in subjects with no history of syncope; about 20% of astronauts, who are selected on the basis of their great resistance to orthostatic stress, experience syncope or presyncope on landing after a short-duration space flight; to date, no genetic basis of VVS has been demonstrated; subjects with VVS are generally normotensive and, importantly, have normal blood pressure regulation apart from the episodes of syncope; hormonal disorders or a generalized state of autonomic involvement, although frequently investigated, have never been clearly demonstrated. Isolated VVS should be distinguished from those forms that start in old age and which are often associated with cardiovascular or neurological disorders, and other dysautonomic disturbances such as carotid sinus hypersensitivity, post-prandial hypotension, and symptoms of autonomic dysfunction. In these subjects, VVS appears as an expression of a pathological process, i.e. a disease, mainly related to a generalized involvement of the autonomic nervous system, which is not yet well-defined from a nosological point of view. PMID- 17272329 TI - Pacemaker and ICD lead extraction with electrosurgical dissection sheaths and standard transvenous extraction systems: results of a randomized trial. AB - AIMS: The purpose of this prospective randomized study was to evaluate the safety and efficacy of transvenous pacemaker and implantable cardioverter-defibrillator (ICD) lead extraction with an electrosurgical dissection sheath (EDS) system in a single-centre experience. Methods Over 10 years, 462 patients have undergone transvenous lead extraction in our institution. From these, 120 consecutive patients (with 161 leads) were randomized to either radiofrequency (RF) current supported extraction or standard countertraction lead removal (60 patients in each arm, 96 men and 24 women). The mean age of randomized patients was 62.7 +/- 9.6 years. In 16 patients, we explanted 17 ICD leads. The average time from the date of implantation to the extraction procedure was 73.4 +/- 15.7 months. The most common reason for lead extraction was infection (95.6%). Results The complete extraction of 78 leads (93%) was achieved in the RF group and 56 leads (73%) with the standard transvenous lead extraction system by counter-traction (P < 0.01). Among these leads, we successfully removed nine of 10 ICD leads (90%) in the RF group and only four of seven ICD leads (57%) in the standard group. We also observed a significant reduction in the time taken for the successful removal of pacemaker and ICD leads using the RF system (9.6 +/- 6.2 min versus 21 +/- 9 min, P < 0.01). Partial success was achieved in six patients with the RF system and in 11 with standard sheaths. In those cases where we failed to remove the lead from the body we sent all but one patient to cardiac surgery. Serious complications were associated with the standard system in two patients, both of whom developed septic pulmonary embolization. Serious bleeding occurred in three patients, one with standard and two with the EDS lead extraction system. CONCLUSION: The EDS extraction system is significantly more effective and quicker. However, the standard counter-traction method is still an effective alternative when used in a highly experienced centre. PMID- 17272330 TI - New technique: repositioning of dislodged atrial pacing lead with a specially designed urological basket. AB - The rate of dislodgement of atrial pacing leads is approximately 3%. To solve this problem, reoperation and repositioning of these leads is one of the solutions. Some operators have reported repositioning these leads with snare systems or deflectable catheters. In this communication, we present a new method using a specially designed urological basket to solve this problem. PMID- 17272331 TI - Acute effects of biventricular pacing on right ventricular function assessed by tissue Doppler imaging. AB - AIMS: The benefits of cardiac resynchronization therapy (CRT) on functional status, left ventricular (LV) remodelling and survival in patients with drug refractory congestive heart failure (CHF), LV systolic dysfunction, and wide QRS have been demonstrated in randomized trials. However, the impact of CRT on right ventricular (RV) function, an independent prognostic factor in CHF remains questionable. This study examined the acute effects of various pacing modes on RV function in recipients of CRT systems. METHODS AND RESULTS: Echocardiographic examinations were performed in 15 patients (median age: 67 years, range 49-78), to compare RV function during atrial (AAI), RV and LV pacing, and biventricular (BiV) pacing, in random order. At baseline, the median LV ejection fraction was 20% (range 10-35) and the median LV end-diastolic diameter was 78 mm (range 62 85). Right ventricular function was impaired, with a median 36% fractional shortening of RV surfaces (7-59). Tissue Doppler systolic peak of velocity (Sa) recorded at the tricuspid annulus increased significantly from 9.9 cm/s (range 4.7-16.5) during AAI pacing, 10 cm/s (range 5.4-20.3) during RV pacing, and 11.7 cm/s (range 4.6-16.7) during LV pacing to 12.6 cm/s (range 6.6-19.1) during BiV pacing (P < 0.01). Trends toward improvements in other indices of RV function, particularly myocardial performance index and systolic excursion of the tricuspid annulus, were also observed. CONCLUSIONS: This short-term study showed a significant improvement in RV systolic function during BiV pacing compared with AAI, RV, or LV pacing in CRT recipients. PMID- 17272332 TI - Pivotal role of integrated electroanatomic mapping with three-dimensional multislice computed tomography scan in the ablation of a left atrial ectopic focus. PMID- 17272333 TI - Common trunk of the inferior pulmonary veins: an unexpected anatomical variant detected before ablation by multi-slice computed tomography. PMID- 17272334 TI - Can transventricular intracardiac impedance measurement discriminate haemodynamically unstable ventricular arrhythmias in human? AB - AIMS: To measure changes in transventricular impedance during arrhythmias. METHODS AND RESULTS: Patients were studied during electrophysiological studies. A quadrapolar catheter was positioned at the right ventricular apex (RVA) and a decapolar catheter within the coronary sinus (CS). Transventricular impedance was measured by injecting a subthreshold biphasic rectangular pulse of 600 micro A between poles 1 of the CS catheter and pole 1 of the RVA catheter and the voltage measured between CS pole 10 and RVA catheter pole 4. Stroke impedance (SZ), surface ECG, intracardiac electrogram (IEGM), and invasive femoral artery blood pressure (FAP) were recorded. Twenty-eight patients were analysed, 5 with inducible, haemodynamically unstable ventricular tachycardia (VT) (HUSVT), 5 with stable VT (HSVT). During HUSVT, the SZ value reduced to 22% (range 0.15-0.32 P < 0.001) in comparison with sinus rhythm. For HSVT, the SZ value reduced to 58% (range 0.33-0.88) P < 0.01, significantly different from HUSVT (P < 0.01). There was a good correlation between reduction of SZ and arterial pulse pressure (PP) during arrhythmias (r = 0.95). CONCLUSION: Changes in SZ strongly correlated with PP amplitude. Transventricular impedance fell significantly during unstable arrhythmias and may be useful as a sensor capable of haemodynamic discrimination. PMID- 17272335 TI - Monomorphic ventricular tachycardia related to Wolff-Parkinson-White surgery. AB - Monomorphic ventricular tachycardia (MVT) is well described in patients who have had a ventricular scar due to repair of congenital heart disease. A 54-year-old woman presented with MVT 20 years after WPW surgery for a left-sided accessory pathway. The circuit was mapped to an area at the base of the left ventricle consistent with the incision described in the operation report. Entrainment confirmed the re-entrant circuit. Successful radiofrequency ablation was performed in a zone of slowed conduction consistent with the circuit isthmus. Any iatrogenic ventricular scar may form the substrate for MVT and be treated with standard electrophysiology techniques. PMID- 17272336 TI - Covering sleeves can shield the high-voltage coils from lead chatter in an integrated bipolar ICD lead. AB - AIMS: Integrated bipolar implantable cardioverter-defibrillator (ICD) leads use the distal high-voltage coil as both the ventricular sensing anode and the distal shocking electrode. Mechanical interactions between the distal ICD coil and other intracardiac leads have been reported to result in electrical oversensing and inappropriate ICD therapies. We sought to determine whether covering sleeves over the high-voltage coils of an integrated bipolar ICD lead could prevent sensed artefact from mechanical lead interactions. METHODS AND RESULTS: Endotak Reliance 0157 and Endotak Reliance-G 0185 leads, the latter with expanded polytetrafluoroethylene (ePTFE) sleeves covering the high-voltage coils, were connected to ICD generators and the leads were submerged in saline. Device programmers were used to communicate with the ICD generators, providing real-time electrogram recording throughout testing. A series of mechanical interactions were performed with the ICD leads, including sliding and striking each distal coil against metal and non-metal components of other ICD and pacemaker leads. All direct metal-metal interactions resulted in sensed electrical artefact, including interactions between the bare ICD coil and another bare ICD coil or metal pacemaker ring. Identical mechanical interactions where metal-metal contact was prevented due to an interposed ePTFE covering sleeve were electrically silent with no sensed artefact. CONCLUSIONS: A covering sleeve over the distal high voltage coil of an integrated bipolar ICD lead can mechanically shield the lead from metal-metal interactions, which might otherwise result in sensed artefact and inappropriate ICD therapies or withholding of pacing output. This finding has implications for lead selection when a new ICD lead is to be implanted adjacent to abandoned intracardiac leads or lead fragments. PMID- 17272337 TI - Monophasic versus biphasic waveform shocks for atrial fibrillation cardioversion in patients with concomitant amiodarone therapy. AB - AIMS: With transthoracic cardioversion of atrial fibrillation (AF), biphasic are more effective than monophasic waveforms. We sought to determine the ideal energy levels for biphasic waveforms. Methods We compared biphasic truncated exponential waveforms with monophasic damped sine waveform defibrillators, in a prospective, single-centre, randomized (1:1 ratio) study. The study included 154 patients receiving concomitant amiodarone; 77 received serial biphasic (50, 100, 150, up to 175 J) and 77 monophasic shocks (100, 200, 300, up to 360 J), as necessary. Results First-shock efficacy was similar in the two groups (57 vs. 55%, P = 0.871, respectively), as were serial-shocks (90 vs. 92%, P = 0.780). Both groups received equal numbers of shocks (1.8 +/- 1.1 vs. 1.7 +/- 1.0, P = 0.921). In both groups, serum creatine kinase levels showed a small but significant increase. The increase was, however, higher in the monophasic group. CONCLUSION: In patients with concomitant amiodarone therapy, biphasic truncated exponential shocks, using half the energy, were as effective as monophasic damped sine shocks. The biphasic scheme was not more efficacious for cardioverting AF. In our population, a first shock of at least 100 J seemed advisable with either waveform. If necessary, escalating shocks must be performed, but ideal levels of increase per shock are still uncertain for biphasic waveforms. PMID- 17272338 TI - Respiratory drive to thoracic motoneurones. PMID- 17272339 TI - Upregulation of AMPK during cold exposure occurs via distinct mechanisms in brown and white adipose tissue of the mouse. AB - AMPK (adenosine monophosphate-activated protein kinase), a key regulator of cellular energy metabolism and whole-body energy balance, is present in brown adipose tissue but its role in regulating the acute metabolic state and chronic thermogenic potential of this metabolically unique tissue is unknown. To address this, the AMPK signalling system in brown and white adipose tissue was studied in C57Bl/6 mice under control conditions, during acute and chronic cold exposure, and during chronic adrenergic stimulation. In control mice AMPK activity in brown adipose tissue was higher than in any tissue yet reported (3-fold the level in liver) secondary to a high level of expression of the alpha1 isoform. During the first day of cold, a time of intense non-shivering thermogenesis, AMPK activity remained at basal levels. However, chronic (>7 days) cold caused a progressive increase in brown adipose tissue AMPK activity secondary to increased expression of the alpha1 isoform. To investigate the signalling pathway involved, noradrenaline (norepinephrine) and the beta(3)-adrenergic-specific agonist CL 316, 243 were given for 14 days. This increased uncoupling protein-1 content in brown adipose tissue, but not AMPK activity. In white adipose tissue 15 days of cold increased alpha1 AMPK activity 98 +/- 20%, an effect reproduced by chronic noradrenaline or CL 316 243. We conclude that chronic cold not only increases AMPK activity in brown and white adipose tissue, but that it does so via distinct signalling pathways. Our data are consistent with AMPK acting primarily as a regulator of chronic thermogenic potential in brown adipose tissue, and not in the acute activation of non-shivering thermogenesis. PMID- 17272341 TI - Pathogenic point mutations in a transmembrane domain of the epsilon subunit increase the Ca2+ permeability of the human endplate ACh receptor. AB - The epsilon subunit of the human endplate ACh receptor (AChR) is a key determinant of the large fraction of the ACh-evoked current carried by Ca2+ ions (P(f)). Consequently, missense mutations in the epsilon subunit are potential targets for altering the P(f) of human AChR. In this paper we investigate the effects of two pathogenic point mutations in the M2 transmembrane segment AChR epsilon subunit, epsilonT264P and epsilonV259F, that cause slow-channel syndromes (SCS). When expressed in GH4C1 cells, the mutant receptors subunits raise Ca2+ permeability of the receptors approximately 1.5 and approximately 2-fold above that of wild-type, to attain P(f) values of 11.8% (epsilonT264P) and 15.4% (epsilonV259F). The latter value exceeds most P(f) values reported to date for ligand-gated ion channels. Consistent with these findings, the biionic Ca2+ permeability ratio (P(Ca)/P(Cs)) of the mutant AChRs is also increased. Upon repetitive stimulation with ACh, the mutant receptors show an enhanced current run-down compared with wild-type, leading to a strong reduction of their function. We propose that the enhanced Ca2+ permeability of the mutant receptors overrides the protective effect of desensitization and, together with the prolonged opening events of the AChR channel, is an important determinant of the excitotoxic endplate damage in the SCS. PMID- 17272340 TI - Voltage-sensitive prestin orthologue expressed in zebrafish hair cells. AB - Prestin, a member of the solute carrier (SLC) family SLC26A, is the molecular motor that drives the somatic electromotility of mammalian outer hair cells (OHCs). Its closest reported homologue, zebrafish prestin (zprestin), shares approximately 70% strong amino acid sequence similarity with mammalian prestin, predicting an almost identical protein structure. Immunohistochemical analysis now shows that zprestin is expressed in hair cells of the zebrafish ear. Similar to mammalian prestin, heterologously expressed zprestin is found to generate voltage-dependent charge movements, giving rise to a non-linear capacitance (NLC) of the cell membrane. Compared with mammalian prestin, charge movements mediated by zprestin display a weaker voltage dependence and slower kinetics; they occur at more positive membrane voltages, and are not associated with electromotile responses. Given this functional dissociation of NLC and electromotility and the structural similarity with mammalian prestin, we anticipate that zprestin provides a valuable tool for tracing the molecular and evolutionary bases of prestin motor function. PMID- 17272342 TI - Recruitment of apical dendritic T-type Ca2+ channels by backpropagating spikes underlies de novo intrinsic bursting in hippocampal epileptogenesis. AB - A single episode of status epilepticus (SE) induced in rodents by the convulsant pilocarpine, produces, after a latent period of > or = 2 weeks, a chronic epileptic condition. During the latent period of epileptogenesis, most CA1 pyramidal cells that normally fire in a regular pattern, acquire low-threshold bursting behaviour, generating high-frequency clusters of 3-5 spikes as their minimal response to depolarizing stimuli. Recruitment of a Ni(2+)- and amiloride sensitive T-type Ca(2+) current (I(CaT)), shown to be up-regulated after SE, plays a critical role in burst generation in most cases. Several lines of evidence suggest that I(CaT) driving bursting is located in the apical dendrites. Thus, bursting was suppressed by focally applying Ni(2+) to the apical dendrites, but not to the soma. It was also suppressed by applying either tetrodotoxin or the K(V)7/M-type K(+) channel agonist retigabine to the apical dendrites. Severing the distal apical dendrites approximately 150 microm from the pyramidal layer also abolished this activity. Intradendritic recordings indicated that evoked bursts are associated with local Ni(2+)-sensitive slow spikes. Blocking persistent Na(+) current did not modify bursting in most cases. We conclude that SE-induced increase in I(CaT) density in the apical dendrites facilitates their depolarization by the backpropagating somatic spike. The I(CaT)-driven dendritic depolarization, in turn, spreads towards the soma, initiating another backpropagating spike, and so forth, thereby creating a spike burst. The early appearance and predominance of I(CaT)-driven low-threshold bursting in CA1 pyramidal cells that experienced SE most probably contribute to the emergence of abnormal network discharges and may also play a role in the circuitry reorganization associated with epileptogenesis. PMID- 17272343 TI - Regulation and function of Ca2+-calmodulin-dependent protein kinase II of fast twitch rat skeletal muscle. AB - The activation and function of Ca(2+)-calmodulin-dependent kinase II (CaMKII) in contracting rat skeletal muscle was examined. The increase in autonomous activity and phosphorylation at Thr(287) of CaMKII of gastrocnemius muscle in response to contractions in situ was rapid and transient, peaking at 1-3 min, but reversed after 30 min of contractions. There was a positive correlation between CaMKII phosphorylation at Thr(287) and autonomous CaMKII activity. In contrast to the rapid and transient increase in autonomous CaMKII activity, the phosphorylation of the putative CaMKII substrate trisk95/triadin was rapid and sustained during contractions. There were no changes in CaMKII activity and phosphorylation or trisk95 phosphorylation in the resting contralateral muscles during stimulation. When fast-twitch muscles were contracted ex vivo, CaMKII inhibition resulted in a greater magnitude of fatigue as well as blunted CaMKII and trisk95 phosphorylation, identifying trisk95 as a physiological CaMKII substrate. In summary, skeletal muscle CaMKII activation was rapid and sustained during exercise/contraction and is mediated by factors within the contracting muscle, probably through allosteric activation via Ca(2+)-CaM. CaMKII may signal through trisk95 to modulate Ca(2+) release in fast-twitch rat skeletal muscle during exercise/contraction. PMID- 17272344 TI - Binding and direct activation of the epithelial Na+ channel (ENaC) by phosphatidylinositides. AB - Several distinct types of ion channels bind and directly respond to phosphatidylinositides, including phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P(3)) and phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P(2)). This regulation is physiologically relevant for its dysfunction, in some instances, causes disease. Recent studies identify the epithelial Na(+) channel (ENaC) as a channel sensitive to phosphatidylinositides. ENaC appears capable of binding both PI(4,5)P(2) and PI(3,4,5)P(3) with binding stabilizing channel gating. The binding sites for these molecules within ENaC are likely to be distinct with the former phosphoinositide interacting with elements in the cytosolic NH(2)-terminus of the beta- and gamma-ENaC subunits and the latter with cytosolic regions immediately following the second transmembrane domains in these two subunits. PI(4,5)P(2) binding to ENaC appears saturated at rest and necessary for channel gating. Thus, decreases in cellular PI(4,5)P(2) levels may serve as a convergence point for inhibitory regulation of ENaC by G-protein coupled receptors and receptor tyrosine kinases. In contrast, apparent PI(3,4,5)P(3) binding to ENaC is not saturated. This enables the channel to respond with gating changes in a rapid and dynamic manner to signalling input that influences cellular PI(3,4,5)P(3) levels. PMID- 17272345 TI - Assistive technology and robotic control using motor cortex ensemble-based neural interface systems in humans with tetraplegia. AB - This review describes the rationale, early stage development, and initial human application of neural interface systems (NISs) for humans with paralysis. NISs are emerging medical devices designed to allow persons with paralysis to operate assistive technologies or to reanimate muscles based upon a command signal that is obtained directly from the brain. Such systems require the development of sensors to detect brain signals, decoders to transform neural activity signals into a useful command, and an interface for the user. We review initial pilot trial results of an NIS that is based on an intracortical microelectrode sensor that derives control signals from the motor cortex. We review recent findings showing, first, that neurons engaged by movement intentions persist in motor cortex years after injury or disease to the motor system, and second, that signals derived from motor cortex can be used by persons with paralysis to operate a range of devices. We suggest that, with further development, this form of NIS holds promise as a useful new neurotechnology for those with limited motor function or communication. We also discuss the additional potential for neural sensors to be used in the diagnosis and management of various neurological conditions and as a new way to learn about human brain function. PMID- 17272346 TI - Outwardly rectifying deflections in threshold electrotonus due to K+ conductances. AB - A transient decrease in excitability occurs regularly during the S1 phase of threshold electrotonus to depolarizing conditioning stimuli for sensory and, less frequently, motor axons. This has been attributed to the outwardly rectifying action of fast K(+) channels, at least in patients with demyelinating diseases. This study investigates the genesis of this notch in healthy axons. Threshold electrotonus was recorded for sensory and motor axons in the median nerve at the wrist in response to test stimuli of different width. The notch occurred more frequently the briefer the test stimulus, and more frequently in sensory studies. In studies on motor axons, the notch decreased in latency and increased in amplitude as the conditioning stimulus increased or the limb was cooled. Low threshold axons displayed profound changes in strength-duration time constant even though the threshold electrotonus curves contained no detectable notch. When a 1.0 ms current was added to subthreshold conditioning stimuli to trigger EMG, the notch varied with the timing and intensity of the brief current pulse. This study finds no evidence for an outwardly rectifying deflection due to K(+) channels, other than the slow accommodation attributable to slow K(+) currents. In normal motor axons, a depolarization-induced notch during the S1 phase of threshold electrotonus is the result of the conditioning stimulus exceeding threshold for some axons. The notch is more apparent in sensory axons probably because of the lower slope of the stimulus-response curve and their longer strength-duration time constant rather than a difference in K(+) conductances. This may also explain the notch in demyelinating diseases. PMID- 17272347 TI - Single-channel properties of glycine receptors of juvenile rat spinal motoneurones in vitro. AB - An essential step in understanding fast synaptic transmission is to establish the activation mechanism of synaptic receptors. The purpose of this work was to extend our detailed single-channel kinetic characterization of alpha1beta glycine channels from rat recombinant receptors to native channels from juvenile (postnatal day 12-16) rat spinal cord slices. In cell-attached patches from ventral horn neurones, 1 mM glycine elicited clusters of channel openings to a single conductance level (41 +/- 1 pS, n = 12). This is similar to that of recombinant heteromers. However, fewer than 1 in 100 cell-attached patches from spinal neurones contained glycine channels. Outside-out patches gave a much higher success rate, but glycine channels recorded in this configuration appeared different, in that clusters opened to three conductance levels (28 +/- 2, 38 +/- 1 and 46 +/- 1 pS, n = 7, one level per cluster, all levels being detected in each patch). Furthermore, open period properties were different for the different conductances. As a consequence of this, the only recordings suitable for kinetic analysis were the cell-attached ones. Low channel density precluded recording at glycine concentrations other than 1 mM, but the 1 mm data allowed us to estimate the fully bound gating constants by global model fitting of the 'flip' mechanism of Burzomato and co-workers. Our results suggest that glycine receptors on ventral horn neurones in the juvenile rat are heteromers and have fast gating, similar to that of recombinant alpha1beta receptors. PMID- 17272348 TI - Dendritic signals from rat hippocampal CA1 pyramidal neurons during coincident pre- and post-synaptic activity: a combined voltage- and calcium-imaging study. AB - The non-linear and spatially inhomogeneous interactions of dendritic membrane potential signals that represent the first step in the induction of activity dependent long-term synaptic plasticity are not fully understood, particularly in dendritic regions which are beyond the reach of electrode measurements. We combined voltage-sensitive-dye recordings and Ca(2+) imaging of hippocampal CA1 pyramidal neurons to study large regions of the dendritic arbor, including branches of small diameter (distal apical and oblique dendrites). Dendritic membrane potential transients were monitored at high spatial resolution and correlated with supra-linear [Ca(2+)](i) changes during one cycle of a repetitive patterned stimulation protocol that typically results in the induction of long term potentiation (LTP). While the increase in the peak membrane depolarization during coincident pre- and post-synaptic activity was required for the induction of supra-linear [Ca(2+)](i) signals shown to be necessary for LTP, the change in the baseline-to-peak amplitude of the backpropagating dendritic action potential (bAP) was not critical in this process. At different dendritic locations, the baseline-to-peak amplitude of the bAP could be either increased, decreased or unaltered at sites where EPSP-AP pairing evoked supra-linear summation of [Ca(2+)](i) transients. We suggest that modulations in the bAP baseline-to-peak amplitude by local EPSPs act as a mechanism that brings the membrane potential into the optimal range for Ca(2+) influx through NMDA receptors (0 to -15 mV); this may require either boosting or the reduction of the bAP, depending on the initial size of both signals. PMID- 17272349 TI - Calcium absorption by Cav1.3 induces terminal web myosin II phosphorylation and apical GLUT2 insertion in rat intestine. AB - Glucose absorption in rat jejunum involves Ca(2+)- and PKC betaII-dependent insertion of GLUT2 into the apical membrane. Ca(2+)-induced rearrangement of the enterocyte cytoskeleton is thought to enhance paracellular flow. We have therefore investigated the relationships between myosin II regulatory light chain phosphorylation (RLC(20)), absorption of glucose, water and calcium, and mannitol clearance. ML-7, an inhibitor of myosin light chain kinase, diminished the phloretin-sensitive apical GLUT2 but not the phloretin-insensitive SGLT1 component of glucose absorption in rat jejunum perfused with 75 mM glucose. Western blotting and immunocytochemistry revealed marked decreases in RLC(20) phosphorylation in the terminal web and in the levels of apical GLUT2 and PKC betaII, but not SGLT1. Perfusion with phloridzin or 75 mM mannitol, removal of luminal Ca(2+), or inhibition of unidirectional (45)Ca(2+) absorption by nifedipine exerted similar effects. ML-7 had no effect on the absorption of 10 mM Ca(2+), nor clearance of [(14)C]-mannitol, which was less than 0.7% of the rate of glucose absorption. Water absorption did not correlate with (45)Ca(2+) absorption or mannitol clearance. We conclude that the Ca(2+) necessary for contraction of myosin II in the terminal web enters via an L-type channel, most likely Ca(v)1.3, and is dependent on SGLT1. Moreover, terminal web RLC(20) phosphorylation is necessary for apical GLUT2 insertion. The data confirm that glucose absorption by paracellular flow is negligible, and show further that paracellular flow makes no more than a minimal contribution to jejunal Ca(2+) absorption at luminal concentrations prevailing after a meal. PMID- 17272350 TI - Apical GLUT2 and Cav1.3: regulation of rat intestinal glucose and calcium absorption. AB - We have proposed a model of intestinal glucose absorption in which transport by SGLT1 induces rapid insertion and activation of GLUT2 in the apical membrane by a PKC betaII-dependent mechanism. Since PKC betaII requires Ca(2+) and glucose is depolarizing, we have investigated whether glucose absorption is regulated by the entry of dietary Ca(2+) through Ca(v)1.3 in the apical membrane. When rat jejunum was perfused with 75 mM glucose, Ca(2+)-deplete conditions, or perfusion with the L-type antagonists nifedipine and verapamil strongly diminished the phloretin sensitive apical GLUT2, but not the phloretin-insensitive SGLT1 component of glucose absorption. Western blotting showed that in each case there was a significant decrease in apical GLUT2 level, but no change in SGLT1 level. Inhibition of apical GLUT2 absorption coincided with inhibition of unidirectional (45)Ca(2+) entry by nifedipine and verapamil. At 10 mM luminal Ca(2+), (45)Ca(2+) absorption in the presence of 75 mM glucose was 2- to 3-fold that in the presence of 75 mM mannitol. The glucose-induced component was SGLT1-dependent and nifedipine-sensitive. RT-PCR revealed the presence of Ca(v)beta(3) in jejunal mucosa; Western blotting and immunocytochemistry localized Ca(v)beta(3) to the apical membrane, together with Ca(v)1.3. We conclude that in times of dietary sufficiency Ca(v)1.3 may mediate a significant pathway of glucose-stimulated Ca(2+) entry into the body and that luminal supply of Ca(2+) is necessary for GLUT2-mediated glucose absorption. The integration of glucose and Ca(2+) absorption represents a complex nutrient-sensing system, which allows both absorptive pathways to be regulated rapidly and precisely to match dietary intake. PMID- 17272351 TI - Role of persistent sodium current in mouse preBotzinger Complex neurons and respiratory rhythm generation. AB - Breathing movements in mammals depend on respiratory neurons in the preBotzinger Complex (preBotC), which comprise a rhythmic network and generate robust bursts that form the basis for inspiration. Persistent Na(+) current (I(NaP)) is widespread in the preBotC and is hypothesized to play a critical role in rhythm generation because of its subthreshold activation and slow inactivation properties that putatively promote long-lasting burst depolarizations. In neonatal mouse slice preparations that retain the preBotC and generate a respiratory-related rhythm, we tested the role of I(NaP) with multiple Na(+) channel antagonists: tetrodotoxin (TTX; 20 nM), riluzole (RIL; 10 microM), and the intracellular Na(+) channel antagonist QX-314 (2 mM). Here we show that I(NaP) promotes intraburst spiking in preBotC neurons but surprisingly does not contribute to the depolarization that underlies inspiratory bursts, i.e. the inspiratory drive potential. Local microinjection in the preBotC of 10 microM RIL or 20 nM TTX does not perturb respiratory frequency, even in the presence of bath applied 100 microM flufenamic acid (FFA), which attenuates a Ca(2+)-activated non specific cation current (I(CAN)) that may also have burst-generating functionality. These data contradict the hypothesis that I(NaP) in preBotC neurons is obligatory for rhythmogenesis. However, in the presence of FFA, local microinjection of 10 microM RIL in the raphe obscurus causes rhythm cessation, which suggests that I(NaP) regulates the excitability of neurons outside the preBotC, including serotonergic raphe neurons that project to, and help maintain, rhythmic preBotC function. PMID- 17272352 TI - Quantitative assessment of human muscle glycogen granules size and number in subcellular locations during recovery from prolonged exercise. AB - Although data relating to muscle glycogen are interpreted as showing it is homogenous when quantified biochemically, it is actually in granules in specific subcellular locations. We hypothesized that postexercise restoration of muscle glycogen would occur initially by an increase in granule number followed by an increase in size, and also that restoration would differ in various subcellular locations. Five men performed prolonged exercise and had muscle biopsies taken at 0, 4, 24 and 48 h of recovery. We quantified granule number and size as well as the total volume of glycogen in the subsarcolemmal and the intra- and intermyofibrillar regions, using transmission electron microscopy. Muscle glycogen was reduced to 36 +/- 8.3 mmol glucosyl units (kg dry weight)(-1) at exhaustion, and was preferentially depleted and subsequently repleted in the intramyofibrillar space. The repletion rate was greatest in the first 4 h; this was associated with a 186% increase in number (P < or = 0.05) and no change in particle size (P > or = 0.05). From 4 h to 48 h, there was an increase in particle size (P < or = 0.05) but not number (P > or = 0.05). Net rate of G volume synthesis per unit area was 50% greater (P < or = 0.05) in the subsarcolemmal than the myofibrillar compartment. Conversely, the net rate of single-particle volume synthesis was greater (P < or = 0.05) in the myofibrillar than the subsarcolemmal compartment. Glycogen granules varied in size and number depending on location, and in all compartments resynthesis of glycogen was characterized initially by an increase in granule number and later by an increase in size. PMID- 17272353 TI - Associative pairing enhances action potential back-propagation in radial oblique branches of CA1 pyramidal neurons. AB - Back-propagating action potentials (bAPs) are involved in associative synaptic plasticity and the modulation of dendritic excitability. We have used high-speed confocal and two-photon imaging to measure calcium and voltage signals associated with action potential propagation into oblique branches of CA1 pyramidal neurons in adult hippocampal slices. The spatial profile of the bAP-associated Ca(2+) influx was biphasic, with an initial increase in the proximity of the branch point followed by a progressive decrease. Voltage imaging in the branches showed that bAP amplitude was initially constant and then steadily declined with distance from the soma. To determine the role of transient K(+) channels in this profile, we used external Ba(2+) (150 microm) as a channel blocker, after characterizing its effect on A-type K(+) channels in the apical trunk. Bath application of Ba(2+) significantly reduced the A-type K(+) current in outside out patches and nearly eliminated the distance-dependent decrease in bAP amplitude and its associated Ca(2+) signal. Finally, small amplitude bAPs at more distal oblique branch locations could be boosted by simultaneous branch depolarization, such that the paired Ca(2+) signal became nearly the same for proximal and distal oblique dendrites. These data suggest that dendritic K(+) channels regulate the amplitude of bAPs to create a dendritic Ca(2+) signal whose magnitude is inversely related to the electrotonic distance from the soma when bAPs are not associated with a significant amount of localized synaptic input. This distance-dependent Ca(2+) signal from bAPs, however, can be amplified and a strong associative signal is produced once the proper correlation between synaptic activation and AP output is achieved. We hypothesize that these two signals may be involved in the regulation of the expression and activity of dendritic voltage- and ligand-gated ion channels. PMID- 17272355 TI - Calpain activation causes a proteasome-dependent increase in protein degradation and inhibits the Akt signalling pathway in rat diaphragm muscle. AB - The role of the calpain proteases in skeletal muscle atrophy is poorly understood. One goal of these experiments was to clarify whether calpains act upstream of the ubiquitin-proteasome pathway (UPP). Calpain activation may also inhibit the anabolic signalling of Akt, since a molecular chaperone previously shown to mediate Akt activity, heat shock protein 90 (HSP 90), is a calpain substrate. Thus, an additional objective was to determine whether calpain activation affects the Akt signalling pathway. Ex vivo experiments were conducted using isolated rat diaphragm muscle. Calpain activation increased total protein degradation by 65%. Proteasome inhibition prevented this large rise in proteolysis, demonstrating that the proteasome was necessary for calpain activated protein degradation. In addition, calpain activation increased proteasome-dependent proteolysis by 144%, further supporting the idea of sequential proteolytic pathways. Calpain reduced Akt and mammalian target of rapamycin (mTOR) phosphorylation by 35 and 50%, respectively, and activated glycogen synthase kinase-3 beta (GSK-3beta) by 40%. Additionally, calpain activation reduced HSP 90beta and mTOR protein content by 33 and 50%, respectively. These data suggest that calpains play a dual role in protein metabolism by concomitantly activating proteasome-dependent proteolysis and inhibiting the Akt pathway of protein synthesis. PMID- 17272356 TI - Physiological regulation of the pancreatic {beta}-cell: functional insights for understanding and therapy of diabetes. AB - Knowledge about the sites and actions of the numerous physiological and pharmacological factors affecting insulin secretion and pancreatic beta-cell function has been derived from the use of bioengineered insulin-producing cell lines. Application of an innovative electrofusion approach has generated novel glucose-responsive insulin-secreting cells for pharmaceutical and experimental research, including popular BRIN-BD11 beta-cells. This review gives an overview of the establishment and core characteristics of clonal electrofusion-derived BRIN-BD11 beta-cells. As discussed, BRIN-BD11 cells have facilitated studies aimed at dissecting important pathways by which nutrients and other bioactive molecules regulate the complex mechanisms regulating insulin secretion, and highlight the future potential of novel and diverse bioengineering approaches to provide a cell-based insulin-replacement therapy for diabetes. Clonal BRIN-BD11 beta-cells have been instrumental in: (a) characterization of K(ATP) channel dependent and -independent actions of nutrients and established and emerging insulinotropic antidiabetic drugs, and the understanding of drug-induced beta cell desensitization; (b) tracing novel metabolic and beta-cell secretory pathways, including use of state-of-the-art NMR approaches to provide new insights into the relationships between glucose and amino acid handling and insulin secretion; and (c) determination of the chronic detrimental actions of nutrients and the diabetic environment on pancreatic beta-cells, including the recent discovery that homocysteine, a risk factor for metabolic syndrome, may play a role in the progressive demise of insulin secretion and pancreatic beta cell function in diabetes. Collectively, the studies discussed in this review highlight the importance of innovative experimental beta-cell physiology in the discovery and characterization of new and improved drugs and therapeutic strategies to help tackle the emerging diabetes epidemic. PMID- 17272354 TI - Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff perfused rabbit hearts. AB - We hypothesize that remodelling of action potential and intracellular calcium (Ca(i)) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Ca(i) and membrane potential (V(m)) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Ca(i) prior to V(m) depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Ca(i) alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Ca(i). Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Ca(i) dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Ca(i) cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting. PMID- 17272357 TI - A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days. AB - AIMS: We sought to test whether an increase in the clopidogrel maintenance dose results in increased inhibition of platelet aggregation. METHODS AND RESULTS: Sixty patients after pre-treatment with 600 mg of clopidogrel and within 12 h after successful PCI were included in this trial. They were allocated to receive one of two clopidogrel daily maintenance doses (75 or 150 mg) for 30 days in a double-blind randomized manner. Platelet function was evaluated 30 days after the intervention with optical aggregometry and with a new point-of-care test (VerifyNowtrade mark P2Y12 assay). Maximal 5 microM ADP-induced platelet aggregation 30 days after PCI in the group treated with 150 mg/day clopidogrel (45.1 +/- 20.9%) was significantly lower than in the group treated with 75 mg/day (65.3 +/- 12.1%; P < 0.001). The VerifyNowtrade mark P2Y12 assay also indicated a higher degree of platelet function inhibition in the group treated with 150 mg/day (60.0 +/- 72.0 P2Y12 Reaction Units) than in the group treated with 75 mg/day (117.0 +/- 64.3 P2Y12 Reaction Units; P = 0.004). CONCLUSION: Administration of a 150 mg oral maintenance dose of clopidogrel results in more intense inhibition of platelet aggregation than administration of the currently recommended 75 mg maintenance dose. PMID- 17272358 TI - Application of a new algorithm in the differential diagnosis of wide QRS complex tachycardia. AB - AIMS: The Brugada criteria proposed to distinguish between regular, monomorphic wide QRS complex tachycardias (WCT) caused by supraventricular (SVT) and ventricular tachycardia (VT) have been reported to have a better sensitivity and specificity than the traditional criteria. By incorporating two new criteria, a new, simplified algorithm was devised and compared with the Brugada criteria. METHODS AND RESULTS: A total of 453 WCTs (331 VTs, 105 SVTs, 17 pre-excited tachycardias) from 287 consecutive patients with a proven electrophysiological (EP) diagnosis were prospectively analysed by two of the authors blinded to the EP diagnosis. The following criteria were analysed: (i) presence of AV dissociation; (ii) presence of an initial R wave in lead aVR; (iii) whether the morphology of the WCT correspond to bundle branch or fascicular block; (iv) estimation of initial (v(i)) and terminal (v(t)) ventricular activation velocity ratio (v(i)/v(t)) by measuring the voltage change on the ECG tracing during the initial 40 ms (v(i)) and the terminal 40 ms (v(t)) of the same bi- or multiphasic QRS complex. A v(i)/v(t) >1 was suggestive of SVT and a v(i)/v(t) or=50 years of age in Nakuru district, Kenya. METHODS: The WHO/PBD VF20 was pilot tested and modified. 196 patients with visual impairment from cataract and 128 population-based controls without visual impairment from cataract were identified through a district-wide survey. Additional cases were identified through case finding. Vision- and health-related quality of life were assessed using the WHO/PBD VF20 scale and EuroQol generic health index (European Quality of Life Questionnaire (EQ-5D)), respectively. WHO/PBD VF20 was evaluated using standard psychometric tests, including factor analysis to determine item grouping for summary scores. RESULTS: The modified WHO/PBD VF20 demonstrated good psychometric properties. Two subscales (general functioning and psychosocial) and one overall eyesight-rating item were appropriate for these data. Increased severity of visual impairment in cases was associated with worsening general functioning, psychosocial and overall eyesight scores (p for trend <0.001). Cases were more likely to report problems with EQ-5D descriptive dimensions than controls (p<0.001), and, among cases, increased severity of visual impairment was associated with worsening self-rated health score. CONCLUSION: The modified WHO/PBD VF20 is a valid and reliable scale to assess vision-related quality of life associated with cataract visual impairment in this Kenyan population. The association between health-related quality of life and visual impairment reflects the wider implications of cataract for health and well-being, beyond visual acuity alone. PMID- 17272389 TI - Suppression of thyrotropin receptor constitutive activity by a monoclonal antibody with inverse agonist activity. AB - TSH binding to the TSH receptor (TSHR) induces thyrocyte growth and proliferation primarily by activating the adenylyl cyclase signaling pathway. Relative to the other glycoprotein hormone receptors, the TSHR has considerable ligand independent (constitutive) activity. We describe a TSHR monoclonal antibody (CS 17) with the previously unrecognized property of being an inverse agonist for TSHR constitutive activity. This property is retained, even when constitutive activity is extremely high consequent to diverse TSHR extracellular region mutations. A similar effect on an activating mutation at the base of the sixth transmembrane helix (not accessible to direct CS-17 contact) indicates that CS-17 is acting allosterically. Administered to mice in vivo, CS-17 reduces serum T(4) levels. The CS-17 epitope is conformational and a significant portion lies in the C-terminal region of the TSHR leucine-rich domain (residues 260-289). By interacting with the large TSHR extracellular domain, CS-17 is, to our knowledge, the first antibody reported to be an inverse agonist for a member of the G protein receptor superfamily. After humanization of its murine constant region, CS-17 has the potential to be an adjunctive therapeutic agent in athyreotic patients with residual well-differentiated thyroid carcinoma as well as pending definitive treatment in some selected hyperthyroidism states. PMID- 17272388 TI - Frequency of bleb manipulations after trabeculectomy surgery. AB - AIM: To quantify the type and frequency of postoperative bleb manipulations undertaken after modern glaucoma surgery. METHODS: Bleb manipulations were recorded after trabeculectomy surgery on 119 consecutive patients with at least 1 year of follow-up. The type of intervention and time after surgery were recorded. Statistical analysis identified success rates at various intraocular pressure (IOP) cut-off definitions and identified factors that increased the risk for bleb manipulation. RESULTS: In all, 78.2% of trabeculectomies were followed by some form of bleb manipulation. Almost 49% of blebs underwent massage and a similar number required at least one suture removal, 31.1% required at least one 5 fluorouracil (5-FU) injection and 25.2% required at least one needling and 5-FU injection. The median time to the first intervention for massage, suture removal, 5-FU injection, and needling and 5-FU injection were 1, 14, 14 and 43 days, respectively. IOP measurements were higher at all follow-up time points in the intervention group. Failure to achieve specific IOP target pressures was also generally poorer in the 5-FU, and needling and 5-FU intervention groups. CONCLUSIONS: Postoperative intervention is a frequent occurrence after modern glaucoma surgery. This requires intensive postoperative follow-up and is a labour intensive undertaking. Despite interventions in our group of patients, IOP in the intervention group was always higher than in the group that required no intervention. PMID- 17272390 TI - A novel inhibitory protein in adipose tissue, the aldo-keto reductase AKR1B7: its role in adipogenesis. AB - The aldo-keto reductase 1B7 (AKR1B7) encodes an aldose-reductase that has been reported as a detoxification enzyme until now. We have demonstrated that AKR1B7 is differently expressed in various mouse white adipose tissues depending on their location. Its expression is associated with a higher ratio of preadipocytes vs. adipocytes. The cells that express AKR1B7 did not contain lipid droplets, and the expression level of akr1b7 was very low in mature adipocytes. We have defined the role of AKR1B7 in adipogenesis using either primary cultures of adipose stromal cells (containing adipocyte precursors) or the 3T3-L1 cell line. Under the same differentiation conditions, adipose stromal cells from tissues that expressed AKR1B7 had a decreased capacity to accumulate lipids compared with those that did not express it. Moreover, the overexpression of sense or antisense AKR1B7 in 3T3-L1 preadipocytes inhibited or accelerated, respectively, their rate of differentiation into adipocytes. In vivo experiments demonstrated that AKR1B7 encoding mRNA expression decreased in adipose tissues from mice where obesity was induced by a high-fat diet. All these results attributed for the first time a novel role to AKR1B7, which is the inhibition of adipogenesis in some adipose tissues. PMID- 17272393 TI - Inhibin A and B in vitro bioactivities are modified by their degree of glycosylation and their affinities to betaglycan. AB - Inhibin A and B, important regulators of normal function in tissues of the reproductive axis, are glycosylated at either Asn(268) or Asn(268) and Asn(302) in the alpha-subunit to produce 31- and 34-kDa isoforms, respectively. In this study, glycosylated isoforms of recombinant human inhibin A and B were purified from conditioned medium using immunoaffinity chromatography and reversed-phase HPLC. The masses of the purified inhibin preparations were determined by several inhibin immunoassays, and their in vitro bioactivities were based on suppression of FSH release by rat pituitary cells in culture. Based on a ratio of in vitro bioactivity to immunoactivity (B:I ratio), the monoglycosylated 31-kDa inhibin A was 5-fold more potent than the diglycosylated 34-kDa inhibin A (B:I ratio, 1.22 +/- 0.15 vs. 0.24 +/- 0.05; P < 0.001, respectively). The 31-kDa inhibin B was significantly (P < 0.001) more potent (1.75 +/- 0.29) than the 34-kDa form (1.08 +/- 0.20). Because inhibin biological activity is dependent upon interactions with the coreceptor betaglycan, the effect of inhibin glycosylation on betaglycan binding was assessed. Analogous to the pattern of in vitro bioactivity, 31-kDa inhibin A was 12-fold more active (IC(50), 0.68 nM) than the 34-kDa isoform (IC(50), 8.2 nM) at displacing [(125)I]inhibin A from COS7 cells expressing betaglycan. However, the 1.6-fold difference in bioactivity of the inhibin B isoforms was not matched by differences in their affinities for betaglycan. It is concluded that glycosylation of Asn(302) of the alpha-subunit of inhibin A and B results in a decrease in bioactivity, and the effect on inhibin A, at least, is explained by its reduced affinity to betaglycan. PMID- 17272392 TI - Prenatal and postnatal pathways to obesity: different underlying mechanisms, different metabolic outcomes. AB - Obesity and type 2 diabetes are worldwide health issues. The present paper investigates prenatal and postnatal pathways to obesity, identifying different metabolic outcomes with different effects on insulin sensitivity and different underlying mechanisms involving key components of insulin receptor signaling pathways. Pregnant Wistar rats either were fed chow ad libitum or were undernourished throughout pregnancy, generating either control or intrauterine growth restricted (IUGR) offspring. Male offspring were fed either standard chow or a high-fat diet from weaning. At 260 d of age, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and other metabolic parameters were measured. As expected, high-fat feeding caused diet-induced obesity (DIO) and insulin resistance. Importantly, the insulin sensitivity of IUGR offspring was similar to that of control offspring, despite fasting insulin hypersecretion and increased adiposity, irrespective of postnatal nutrition. Real-time PCR and Western blot analyses of key markers of insulin sensitivity and metabolic regulation showed that IUGR offspring had increased hepatic levels of atypical protein kinase C zeta (PKC zeta) and increased expression of fatty acid synthase mRNA. In contrast, DIO led to decreased expression of fatty acid synthase mRNA and hepatic steatosis. The decrease in hepatic PKC zeta with DIO may explain, at least in part, the insulin resistance. Our data suggest that the mechanisms of obesity induced by prenatal events are fundamentally different from those of obesity induced by postnatal high-fat nutrition. The origin of insulin hypersecretion in IUGR offspring may be independent of the mechanistic events that trigger the insulin resistance commonly observed in DIO. PMID- 17272391 TI - Follice-stimulating hormone receptor forms oligomers and shows evidence of carboxyl-terminal proteolytic processing. AB - FSH receptor (FSHR), a member of the G protein-coupled receptor superfamily, is present in the plasma membrane of ovarian granulosa cells and testicular Sertoli cells. FSH regulates normal ovarian follicle development and spermatogenesis through FSHR. The extracellular domain of FSHR is a weakly associated homodimer in the recently solved crystal structure of FSH in complex with the extracellular domain of FSHR. However, there is currently no biochemical data that demonstrate that FSHR exists as a dimer or higher-order oligomer in cell membranes. A fluorescence resonance energy transfer assay was used to determine whether full length native FSHR is an oligomer. FSHR-specific monoclonal antibody or Fab fragments, labeled with two different fluorophores, allowed the study of nontagged receptor in situ. Unoccupied FSHR exhibited strong fluorescence resonance energy transfer profiles in situ. Complementary coimmunoprecipitation experiments of myc- or FLAG-tagged FSHR indicated that FSHR forms oligomers early in receptor biosynthesis. No effect of FSH treatment was observed. Thus, immature forms of FSHR, not yet fully processed, were observed to coimmunoprecipitate. An unexpected observation was made that the C-terminal epitope tags are removed from FSHR before arrival at the cell surface. These results provide the first evidence for oligomers of full-length FSHR in situ and for C-terminal proteolytic processing of FSHR and that both events take place during biosynthesis. This may explain how heterozygous mutations in the FSHR gene that affect receptor trafficking may be ameliorated by oligomer formation. PMID- 17272394 TI - Testosterone activates mitogen-activated protein kinase via Src kinase and the epidermal growth factor receptor in sertoli cells. AB - A new pathway of testosterone (T) action in Sertoli cells was recently identified that may be required to support spermatozoa production (spermatogenesis) and fertility. Specifically, T acts via the androgen receptor (AR) to rapidly activate the MAPK cascade and the cAMP response element-binding protein (CREB) transcription factor in Sertoli cells. In further characterizing the signaling pathway that transduces T actions, we now find that a population of AR is localized to the plasma membrane and that AR associates with Src kinase after T stimulation. In addition, we demonstrate that Src kinase is activated by T and that Src kinase activity is required for stimulation of the ERK MAPK and CREB. Furthermore, we determine that activation of the epidermal growth factor receptor downstream of Src contributes to the activation of the MAPK cascade and CREB. The elucidation of this nonclassical pathway of T action in the testis may provide new targets for the control of male fertility. PMID- 17272395 TI - Fasting inhibits the growth and reproductive axes via distinct Y2 and Y4 receptor mediated pathways. AB - Neuropeptide Y, a neuropeptide abundantly expressed in the brain, has been implicated in the regulation of the hypothalamo-pituitary-somatotropic axis and the hypothalamo-pituitary-gonadotropic axis. Elevated hypothalamic neuropeptide Y expression, such as that occurs during fasting, is known to inhibit both of these axes. However, it is not known which Y receptor(s) mediate these effects. Here we demonstrate, using Y receptor knockout mice, that Y2 and Y4 receptors are separately involved in the regulation of these axes. Fasting-induced inhibition of hypothalamic GHRH mRNA expression and reduction of circulating IGF-I levels were observed in wild-type and Y4(-/-) mice but not Y2(-/-) or Y2(-/-)Y4(-/-) mice. In contrast, fasting-induced reduction of GnRH expression in the medial preoptic area and testis testosterone content were abolished in the absence of Y4 receptors. Colocalization of Y2 receptors and GHRH in the arcuate nucleus (Arc) suggests that GHRH mRNA expression in this region might be directly regulated by Y2 receptors. Indeed, hypothalamic-specific deletion of Y2 receptors in conditional knockout mice prevented the fasting-induced reduction in Arc GHRH mRNA expression. On the other hand, fasting-induced decrease in GnRH mRNA expression in the medial preoptic area is more likely indirectly influenced by Y4 receptors because no Y4 receptors could be detected on GnRH neurons in this region. Together these data show that fasting inhibits the somatotropic axis via direct action on Y2 receptors in the Arc and indirectly inhibits the gonadotropic axis via Y4 receptors. PMID- 17272396 TI - Estrogen-induced activation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor expression, and edema in the uterus are mediated by the phosphatidylinositol 3-kinase/Akt pathway. AB - Vascular endothelial growth factor (VEGF) plays an essential role in normal uterine physiology and function as well as endometrial cancer and other uterine disorders. Recently we showed that estrogen regulation of VEGF expression in the rat uterus involves rapid recruitment of both estrogen receptor (ER)-alpha and hypoxia-inducible factor (HIF)-1alpha to the VEGF promoter. Estrogen is known to stimulate both the MAPK and phosphatidylinositol 3-kinase (PI3K) pathways, which have been linked to the activation of both of these transcription factors. Therefore, the involvement of these pathways in estrogen-induced VEGF expression was investigated. Inhibitors of the MAPK (U0126) or PI3K pathways (wortmannin or LY294002) were administered ip to immature female rats 1 h before 17beta estradiol (E(2)) treatment. E(2) activation of both pathways occurred and was completely inhibited by the appropriate antagonist. Only PI3K inhibitors, however, blocked E(2) stimulation of VEGF mRNA expression and E(2)-induced uterine edema. In vivo chromatin immunoprecipitation analysis showed that this was associated with a failure of both HIF-1alpha and ERalpha to bind to the VEGF promoter. To determine whether inhibiting the PI3K pathway affected ERalpha induction of other estrogen target genes, the expression of creatine kinase B and progesterone receptor A/B was also examined. The expression of each was also inhibited by wortmannin, as was ERalpha binding to the creatine kinase B promoter. In conclusion, although estrogen activates both the MAPK and PI3K pathways in the rat uterus, activation of HIF-1alpha and ERalpha, and therefore regulation of VEGF gene expression is dependent only on the PI3K/Akt pathway. Furthermore, activation of the PI3K pathway appears to be a common requirement for the expression of estrogen-induced genes. These findings not only shed light on estrogen action in normal target tissues but also have important implications for cancer biology because excessive PI3K, HIF-1alpha, and VEGF activity are common in estrogen-dependent tumors. PMID- 17272397 TI - Regulation of growth hormone signaling by selective estrogen receptor modulators occurs through suppression of protein tyrosine phosphatases. AB - Activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) pathway by GH is terminated by the suppressors of cytokine signaling (SOCSs) and protein tyrosine phosphatases, Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 and SHP-2. Based on our recent report that estrogen inhibits GH signaling by stimulating SOCS-2 expression, we investigated the effects of selective estrogen receptor modulators (SERMs) on GH signaling in human embryonic kidney (HEK293) and breast cancer (MDA MB-231) cells expressing human GH receptor and estrogen receptor-alpha. 17beta estradiol (E(2)) suppressed GH activation of a STAT5-responsive luciferase reporter and JAK2 phosphorylation in both cell models. 4-hydroxytamoxifen and raloxifene augmented these actions of GH in HEK293 cells but not breast cancer cells. SOCS-2 expression in both cell types was stimulated by E(2) but unaffected by SERMs. In HEK293 cells, SHP-1 was inhibited by raloxifene and 4 hydroxytamoxifen, whereas the latter additionally inhibited SHP-2. The phosphatases were unaffected by E(2). In breast cancer cells, phosphatase activity was not altered by SERMs or E(2). In summary, estrogen inhibited the JAK2/STAT5 signaling of GH and stimulated SOCS-2 expression in both HEK293 and breast cancer cells. By contrast, SERMs augmented GH signaling by reducing SHP activities in HEK293 cells and had no effect on both in breast cancer cells. We provide the first evidence for a novel mechanism regulating GH signaling, in which SERMs enhance GH activation of the JAK2/STAT5 pathway in a cell-type dependent manner by attenuating protein tyrosine phosphatase activities. PMID- 17272398 TI - Identification of the glomerular podocyte as a target for growth hormone action. AB - GH excess in both the human and transgenic animal models is characterized by significant changes in blood pressure and renal function. The GH/GH receptor (GHR) axis is also implicated in the development of diabetic nephropathy. However, it is not clear whether GH's actions on renal function are due to indirect actions mediated via changes in blood pressure and vascular tone or due to direct action of GH on the kidney. We hypothesized that functional GHRs are expressed on the glomerular podocyte enabling direct actions of GH on glomerular function. Real-time PCR, immunohistochemistry, and Western blot analysis of murine podocyte cells (MPC-5) and kidney glomeruli demonstrated expression of GHR mRNA and protein. Exposure of both murine and human podocytes to GH (50-500 ng/ml) resulted in an increase in abundance of phosphorylated signal transducer and activator of transcription-5, Janus kinase-2, and ERK1/2 proteins. Exposure of podocytes to GH also caused changes in the intracellular distribution of the Janus kinase-2 adapter protein Src homology 2-Bbeta, stimulation of focal adhesion kinase, increase in reactive oxygen species, and GH-dependent changes in the actin cytoskeleton. We conclude that glomerular podocytes express functional GHRs and that GH increases levels of reactive oxygen species and induces reorganization of the actin cytoskeleton in these cells. These results provide a novel mechanistic link between GH's actions and glomerular dysfunction in disorders such as acromegaly and diabetic glomerulosclerosis. PMID- 17272399 TI - Coexpression of somatostatin receptor subtype 5 affects internalization and trafficking of somatostatin receptor subtype 2. AB - The somatostatin [somatotropin release-inhibiting factor (SRIF)] receptor subtypes sst(2A) and sst(5) are frequently coexpressed in SRIF-responsive cells, including endocrine pituitary cells. We previously demonstrated that sst(2A) and sst(5) exhibit different subcellular localizations and regulation of cell surface expression, although they have similar signaling properties. We investigated here whether sst(2A) and sst(5) functionally interact in cells coexpressing the two receptor subtypes. We stimulated both transfected cells stably expressing sst(2A) alone (CHO-sst(2A)) or together with sst(5) (CHO-sst(2A+5)) and the pituitary cell line AtT20, which endogenously expresses the two receptor subtypes, with either the nonselective agonist [D-Trp(8)]-SRIF-14 or the sst(2)-selective agonist L-779,976. In CHO-sst(2A) cells, stimulation with either ligand resulted in the loss of approximately 75% of cell surface SRIF binding sites and massive internalization of sst(2A) receptors. The cells were desensitized to subsequent stimulation with [D-Trp(8)]-SRIF-14, which failed to inhibit forskolin-evoked cAMP accumulation. Similarly, in CHO-sst(2A+5) and AtT20 cells, [D-Trp(8)]-SRIF 14 induced the loss of 60-70% of SRIF binding sites as well as massive sst(2A) endocytosis. By contrast, in cells expressing both sst(2A) and sst(5), selective stimulation of sst(2A) with L-779,976 resulted in only 20-40% loss of cell surface binding and markedly reduced sst(2A) internalization. Consequently, whereas CHO-sst(2A+5) and AtT20 cells stimulated with [D-Trp(8)]-SRIF-14 were desensitized to a second stimulation with the same agonist, cells prestimulated with L-779,976 were not desensitized to subsequent [D-Trp(8)]-SRIF-14 stimulation. These findings indicate that the presence of sst(5) in the same cells modulates trafficking and cell surface regulation of sst(2A) and cellular desensitization to the effects of SRIF. PMID- 17272400 TI - Depot-specific modulation of rat intraabdominal adipose tissue lipid metabolism by pharmacological inhibition of 11beta-hydroxysteroid dehydrogenase type 1. AB - The metabolic consequences of visceral obesity have been associated with amplification of glucocorticoid action by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue. This study aimed to assess in a rat model of diet-induced obesity the effects of pharmacological 11beta-HSD1 inhibition on the morphology and expression of key genes of lipid metabolism in intraabdominal adipose depots. Rats fed a high-sucrose, high-fat diet were treated or not with a specific 11beta-HSD1 inhibitor (compound A, 3 mg/kg.d) for 3 wk. Compound A did not alter food intake or body weight gain but specifically reduced mesenteric adipose weight (-18%) and adipocyte size, without significantly affecting those of epididymal or retroperitoneal depots. In mesenteric fat, the inhibitor decreased (to 25-50% of control) mRNA levels of genes involved in lipid synthesis (FAS, SCD1, DGAT1) and fatty acid cycling (lipolysis/reesterification, ATGL and PEPCK) and increased (30%) the activity of the fatty acid oxidation-promoting enzyme carnitine palmitoyltransferase 1. In striking contrast, in the epididymal depot, 11beta-HSD1 inhibition increased (1.5-5-fold) mRNA levels of those genes related to lipid synthesis/cycling and slightly decreased carnitine palmitoyltransferase 1 activity, whereas gene expression remained unaffected in the retroperitoneal depot. Compound A robustly reduced liver triacylglycerol content and plasma lipids. The study demonstrates that pharmacological inhibition of 11beta-HSD1, at a dose that does not alter food intake, reduces fat accretion specifically in the mesenterical adipose depot, exerts divergent intraabdominal depot-specific effects on genes of lipid metabolism, and reduces steatosis and lipemia. PMID- 17272401 TI - Identification of the endogenous ligands for chicken growth hormone-releasing hormone (GHRH) receptor: evidence for a separate gene encoding GHRH in submammalian vertebrates. AB - It is generally believed that hypothalamic GHRH activates GHRH receptor (GHRHR) to stimulate GH synthesis and release in the pituitary of mammals. However, the identity of the endogenous ligand of GHRHR is still unresolved in submammalian vertebrates including birds. In this study, we have successfully identified the chicken GHRH (cGHRH) gene, which consists of seven exons including two exons (exons 4 and 5) coding for the predicted mature GHRH peptide of 47 amino acids. Interestingly, the differential usage of splice donor sites at exon 6 results in the generation of two prepro-GHRHs (172 and 188 amino acids in length) with different C-terminal tails. Similar to mammals, cGHRH was detected to be predominantly expressed in the hypothalamus by RT-PCR assay. Using the pGL3-CRE luciferase reporter system, we further demonstrated that both the synthetic cGHRH peptides (cGHRH(1-47) and cGHRH(1-31)) and conditioned medium from CHO cells expressing cGHRH could strongly induce luciferase activity via activation of cGHRHR, indicating that cGHRH could bind cGHRHR and activate downstream cAMP protein kinase A signaling pathway. Using the same system, cGHRH-like peptide was also shown to be capable of activating cGHRHR in vitro. As in chicken, a conserved GHRH gene was identified in the genomes of lower vertebrate species including zebrafish, fugu, tetraodon, and Xenopus by synteny analysis. Collectively, our data suggest that GHRH, perhaps together with GHRH-like peptide (chicken/carp-like), may function as the authentic endogenous ligands of GHRHR in chicken as well as in other lower vertebrate species. PMID- 17272403 TI - Reducing susceptibility to bacteremia after experimental burn injury: a role for selective decontamination of the digestive tract. AB - We proposed that selective decontamination of the digestive tract (SDD) initiated after experimental burn injury would decrease myocardial inflammation and dysfunction after a second insult such as septic challenge. Rats were divided into eight experimental groups. Groups included sham burn plus sham sepsis, burn alone, sepsis alone, and burn plus sepsis given either water by oral gavage for 5 days after burn (or sham burn) or given oral antibiotics (polymyxin E, 15 mg; tobramycin, 6 mg; 5-flucytosin, 100 mg given by oral gavage, 2x daily for 5 days after burn or sham burn). Cardiac function and inflammation were studied 24 h after septic challenge. In the absence of SDD, burn alone, sepsis alone, or burn plus septic challenge promoted cardiac myocyte secretion of TNF-alpha (burn, 174+/-11; sepsis, 269+/-19; burn+sepsis, 453+/-14 pg/ml), IL-1beta (burn, 35+/-2; sepsis, 29+/-1; burn+sepsis, 48+/-7 pg/ml), and IL-6 (burn, 143+/-18; sepsis, 116+/-3; burn+sepsis, 248+/-12 pg/ml) compared with values measured in sham (TNF alpha, 3+/-1; IL-1beta, 1+/-0.4; IL-6, 6+/-1.5 pg/ml) (P<0.05). Impaired ventricular contraction and relaxation responses were evident in the absence of SDD [burn+sepsis: left ventricular pressure (LVP), 65+/-4 mmHg; rate of LVP rise (+dP/dt), 1,320+/-131 mmHg/s compared with values measured in sham: LVP, 96+/-4 mmHg; +dP/dt, 2,095+/-99 mmHg/s, P<0.05]. SDD treatment of experimental burn attenuated septic challenge-related inflammatory responses and improved myocardial contractile responses, producing cardiac TNF-alpha, IL-1beta, and IL-6 levels, LVP, +dP/dt, and rate of LVP fall (-dP/dt) values that were significantly better (P<0.05) than values measured in burn plus sepsis in the absence of SDD. This work confirms that endogenous gut organisms contribute to sensitivity to subsequent infectious challenge. PMID- 17272402 TI - Tissue kallikrein reverses insulin resistance and attenuates nephropathy in diabetic rats by activation of phosphatidylinositol 3-kinase/protein kinase B and adenosine 5'-monophosphate-activated protein kinase signaling pathways. AB - We previously reported that iv delivery of the human tissue kallikrein (HK) gene reduced blood pressure and plasma insulin levels in fructose-induced hypertensive rats with insulin resistance. In the current study, we evaluated the potential of a recombinant adeno-associated viral vector expressing the HK cDNA (rAAV-HK) as a sole, long-term therapy to correct insulin resistance and prevent renal damage in streptozotocin-induced type-2 diabetic rats. Administration of streptozotocin in conjunction with a high-fat diet induced systemic hypertension, diabetes, and renal damage in rats. Delivery of rAAV-HK resulted in a long-term reduction in blood pressure, and fasting plasma insulin was significantly lower in the rAAV-HK group than in the control group. The expression of phosphatidylinositol 3-kinase p110 catalytic subunit and the levels of phosphorylation at residue Thr-308 of Akt, insulin receptor B, and AMP-activated protein kinases were significantly decreased in organs from diabetic animals. These changes were significantly attenuated after rAAV-mediated HK gene therapy. Moreover, rAAV-HK significantly decreased urinary microalbumin excretion, improved creatinine clearance, and increased urinary osmolarity. HK gene therapy also attenuated diabetic renal damage as assessed by histology. Together, these findings demonstrate that rAAV HK delivery can efficiently attenuate hypertension, insulin resistance, and diabetic nephropathy in streptozotocin-induced diabetic rats. PMID- 17272404 TI - Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice. AB - Obstructive sleep apnea is associated with increased risk for cardiovascular diseases. As obstructive sleep apnea is characterized by episodic cycles of hypoxia and normoxia during sleep, we investigated effects of intermittent hypoxia (IH) on ischemia-reperfusion-induced myocardial injury. C57BL/6 mice were subjected to IH (2 min 6% O(2) and 2 min 21% O(2)) for 8 h/day for 1, 2, or 4 wk; isolated hearts were then subjected to ischemia-reperfusion. IH for 1 or 2 wk significantly enhanced ischemia-reperfusion-induced myocardial injury. However, enhanced cardiac damage was not seen in mice treated with 4 wk of IH, suggesting that the heart has adapted to chronic IH. Ischemia-reperfusion-induced lipid peroxidation and protein carbonylation were enhanced with 2 wk of IH, while, with 4 wk, oxidative stress was normalized to levels in animals without IH. H(2)O(2) scavenging activity in adapted hearts was higher after ischemia-reperfusion, suggesting the increased antioxidant capacity. This might be due to the involvement of thioredoxin, as the expression level of this protein was increased, while levels of other antioxidant enzymes were unchanged. In the heart from mice treated with 2 wk of IH, ischemia-reperfusion was found to decrease thioredoxin. Ischemia-reperfusion injury can also be enhanced when thioredoxin reductase was inhibited in control hearts. These results demonstrate that IH changes the susceptibility of the heart to oxidative stress in part via alteration of thioredoxin. PMID- 17272405 TI - Does local heating-induced nitric oxide production attenuate vasoconstrictor responsiveness to lower body negative pressure in human skin? AB - We tested the hypothesis that local heating-induced nitric oxide (NO) production attenuates cutaneous vasoconstrictor responsiveness. Eleven subjects (6 men, 5 women) had four microdialysis membranes placed in forearm skin. Two membranes were perfused with 10 mM of N(G)-nitro-L-arginine (L-NAME) and two with Ringer solution (control), and all sites were locally heated to 34 degrees C. Subjects then underwent 5 min of 60-mmHg lower body negative pressure (LBNP). Two sites (a control and an L-NAME site) were then heated to 39 degrees C, while the other two sites were heated to 42 degrees C. At the L-NAME sites, skin blood flow was elevated using 0.75-2 mg/ml of adenosine in the perfusate solution (Adn + L-NAME) to a similar level relative to control sites. Subjects then underwent another 5 min of 60-mmHg LBNP. At 34 degrees C, cutaneous vascular conductance (CVC) decreased (Delta) similarly at both control and L-NAME sites during LBNP (Delta7.9 +/- 3.0 and Delta3.4 +/- 0.8% maximum, respectively; P > 0.05). The reduction in CVC to LBNP was also similar between control and Adn + L-NAME sites at 39 degrees C (control Delta11.4 +/- 2.5 vs. Adn + L-NAME Delta7.9 +/- 2.0% maximum; P > 0.05) and 42 degrees C (control Delta1.9 +/- 2.7 vs. Adn + L-NAME Delta 4.2 +/- 2.7% maximum; P > 0.05). However, the decrease in CVC at 42 degrees C, regardless of site, was smaller than at 39 degrees C (P < 0.05). These results do not support the hypothesis that local heating-induced NO production attenuates cutaneous vasoconstrictor responsiveness during high levels of LBNP. However, elevated local temperature, per se, attenuates cutaneous vasoconstrictor responsiveness to LBNP, presumably through non-nitric oxide mechanisms. PMID- 17272406 TI - Ventilatory sensitivity to carbon dioxide before and after episodic hypoxia in women treated with testosterone. AB - We hypothesized that the ventilatory threshold and sensitivity to carbon dioxide in the presence of hypoxia and hyperoxia during wakefulness would be increased following testosterone administration in premenopausal women. Additionally, we hypothesized that the sensitivity to carbon dioxide increases following episodic hypoxia and that this increase is enhanced after testosterone administration. Eleven women completed four modified carbon dioxide rebreathing trials before and after episodic hypoxia. Two rebreathing trials before and after episodic hypoxia were completed with oxygen levels sustained at 150 Torr, the remaining trials were repeated while oxygen was maintained at 50 Torr. The protocol was completed following 8-10 days of treatment with testosterone or placebo skin patches. Resting minute ventilation was greater following treatment with testosterone compared with placebo (testosterone 11.38 +/- 0.43 vs. placebo 10.07 +/- 0.36 l/min; P < 0.01). This increase was accompanied by an increase in the ventilatory sensitivity to carbon dioxide in the presence of sustained hyperoxia (VSco(2)(hyperoxia)) compared with placebo (3.6 +/- 0.5 vs. 2.9 +/- 0.3; P < 0.03). No change in the ventilatory sensitivity to carbon dioxide in the presence of sustained hypoxia (VSco(2 hypoxia)) following treatment with testosterone was observed. However, the VSco(2 hypoxia) was increased after episodic hypoxia. This increase was similar following treatment with placebo or testosterone patches. We conclude that treatment with testosterone leads to increases in the VSco(2)(hyperoxia), indicative of increased central chemoreflex responsiveness. We also conclude that exposure to episodic hypoxia enhances the VSco(2 hypoxia), but that this enhancement is unaffected by treatment with testosterone. PMID- 17272407 TI - Microchambers and macrochambers in heel pads: are they functionally different? AB - The heel pad consists of a superficial microchamber layer and a deep macrochamber layer. This study highlights the different biomechanical behaviors between the microchamber and macrochamber layers using ultrasonography. The heel pad in each left foot of six healthy volunteers aged approximately 25 yr old was measured with a device consisting of a 10-MHz linear-array ultrasound transducer and a load cell. The testing heels were loaded on the ultrasound transducer with a loading velocity of approximately 0.5 cm/s and were withdrawn when the specified maximum stress (158 kPa) was reached. Unloaded tissue thickness, end-loaded thickness, deformation proportion, average deformation, and rebound rates and elastic modulus of the microchamber and macrochamber layers were assessed. The unloaded thickness of the microchamber layer was approximately 30% of the macrochamber layer. The microchamber layer also had significantly less unloaded thickness, end-loaded thickness, mean deformation rate, mean rebound rate, and deformation proportion than the macrochamber layer. A significant difference between the unloaded and end-loaded thickness in the macrochamber layer was observed. The average soft tissue deformation rate was significantly different from the rebound rate in the microchamber layer. A similar trend was detected in the macrochamber layer. The elastic modulus of the microchamber layer was 450 kPa (SD 240), which was nearly 10 times of that in the macrochamber layer. In conclusion, ultrasound can identify the heterogeneous tissue properties of the heel pad. The macrochamber layer responds to loading with large deformation, and the microchamber layer has a high degree of tissue stiffness. PMID- 17272408 TI - Prevention of pressure-induced deep tissue injury using intermittent electrical stimulation. AB - Pressure ulcers develop due to morphological and biochemical changes triggered by the combined effects of mechanical deformation, ischemia, and reperfusion that occur during extended periods of immobility. The goal of this study was to test the effectiveness of a novel electrical stimulation technique in the prevention of deep tissue injury (DTI). We propose that contractions elicited by intermittent electrical stimulation (IES) in muscles subjected to constant pressure would induce periodic relief in internal pressure; additionally, each contraction would also restore blood flow to the tissue. The application of constant pressure to the quadriceps muscles of rats generated a DTI that affected 60 +/- 15% of the compressed muscle as assessed by magnetic resonance imaging. In contrast, in the groups of rats that received IES at 10- and 5-min intervals, DTI of the muscle was limited to 16 +/- 16 and 25 +/- 13%, respectively. Injury to the muscle was corroborated by histology. In an experiment with a human volunteer, compression of the buttocks reduced the oxygenation level of the muscles by approximately 4%; after IES, oxygenation levels increased by approximately 6% beyond baseline. Concurrently, the surface pressure profiles of the loaded muscles were redistributed and the high-pressure points were reduced during each IES-induced contraction. The results of this study indicate that IES significantly reduces the amount of DTI by increasing the oxygen available to the tissue and by modifying the pressure profiles of the loaded muscles. This presents a promising technique for the prevention of pressure ulcers in immobilized and/or insensate individuals. PMID- 17272409 TI - Susceptibility to pulmonary hypertension in inbred strains of mice exposed to cigarette smoke. AB - Cor pulmonale is a significant cause of morbidity and mortality in patients with emphysema, but it is not known whether alveolar destruction is directly involved in the disease pathogenesis. The purpose of this study was to examine the relationship between susceptibility to smoking-induced cor pulmonale and alveolar destruction in eight inbred strains of mice: 129XI/SvJ, A/J, A/HeJ, BALB/cJ, C3H/HeJ, C57BL/6J, DBA/2J, and SWR/J. The mice were exposed to filtered air or mainstream cigarette smoke at a concentration of 250 mg/m(3) for 5.5 h/day, 5 days/wk for 5 mo, housed for 4 more months, and killed. The ratio of the weight of the right ventricle/left ventricle plus septum [RV/(LV + S)] was used to assess right ventricular hypertrophy. Alveolar mean linear intercept was used to quantify severity of alveolar destruction. Morphometric determination of blood vessel muscularization was done on sections from four mouse strains. Smoke exposure resulted in significant increases in RV/(LV + S) in the A/J and A/HeJ strains compared with air-exposed controls. The magnitude of the smoking-induced increase in RV/(LV + S) decreased as a function of the genetic distance of the other strains from the A/J and A/HeJ strains. Pulmonary vascular muscularization was significantly increased in smoke-exposed A/J and BALB/cJ mice but not in C3H/HeJ and C57BL/6 mice. Also, mouse strain susceptibility to smoking-induced pulmonary vascular muscularization did not correlate with changes in mean linear intercept. The data from this study suggest that alveolar destruction by itself is not sufficient to cause smoking-induced cor pulmonale in inbred mice. PMID- 17272410 TI - Effects of activation pattern on nonisometric human skeletal muscle performance. AB - During volitional muscle activation, motor units often fire with varying discharge patterns that include brief, high-frequency bursts of activity. These variations in the activation rate allow the central nervous system to precisely control the forces produced by the muscle. The present study explores how varying the instantaneous frequency of stimulation pulses within a train affects nonisometric muscle performance. The peak excursion produced in response to each stimulation train was considered as the primary measure of muscle performance. The results showed that at each frequency tested between 10 and 50 Hz, variable frequency trains that took advantage of the catchlike property of skeletal muscle produced greater excursions than constant-frequency trains. In addition, variable frequency trains that could achieve targeted trajectories with fewer pulses than constant-frequency trains were identified. These findings suggest that similar to voluntary muscle activation patterns, varying the instantaneous frequency within a train of pulses can be used to improve muscle performance during functional electrical stimulation. PMID- 17272411 TI - Polymorphisms in the CNTF and CNTF receptor genes are associated with muscle strength in men and women. AB - Genotypic associations between polymorphisms in the ciliary neurotrophic factor (CNTF) and CNTF receptor (CNTFR) genes and muscular strength phenotypes in 154 middle-aged men (45-49 yr) and 138 women (38-44 yr) and 99 older men (60-78 yr) and 102 older women (60-80 yr) were tested to validate earlier association studies. Allelic interaction effects were hypothesized between alleles of CNTF and CNTFR. We performed analysis of covariance with age, height, and fat-free mass (FFM) as covariates. FFM was anthropometrically estimated by the equation of Durnin-Womersley. Isometric, concentric, and eccentric torques for the knee flexors (KF) and extensors (KE) were measured using Biodex dynamometry. In the older male group, T-allele carriers of the C-1703T polymorphism in CNTFR performed significantly better on all noncorrected KF torques, whereas only noncorrected KE isometric torque at 120 degrees and concentric torque at 240 degrees/s were higher than the C/C homozygotes (P < 0.05). When age, height, and FFM were used as covariates, T-allele carriers performed only better on KE and KF isometric torque at 120 degrees (P < 0.05). Concentric KF torque at 180 degrees/s was lower in middle-aged female A-allele carriers compared with the T/T subjects for the T1069A polymorphism in CNTFR. After correction for age, height, and FFM, middle-aged female A-allele carriers exhibited lower values on all concentric KF strength measures and isometric torque at 120 degrees . There was a lack of association with the CNTF G-6A polymorphism in men, with inconclusive results for a limited number of phenotypes in women. No significant CNTF/CNTFR allele interaction effects were found. Results indicate that CNTFR C-1703T and T1069A polymorphisms are significantly associated with muscle strength in humans. PMID- 17272412 TI - Muscle glycogen oxidation during prolonged exercise measured with oral [13C]glucose: comparison with changes in muscle glycogen content. AB - Plasma glucose and muscle glycogen oxidation during prolonged exercise [75-min at 48 and 76% maximal O(2) uptake (Vo(2 max))] were measured in eight well-trained male subjects [Vo(2 max) = 4.50 l/min (SD 0.63)] using a simplified tracer technique in which a small amount of glucose highly enriched in (13)C was ingested: plasma glucose oxidation was computed from (13)C/(12)C in plasma glucose (which was stable beginning at minute 30 and minute 15 during exercise at 48 and 76% Vo(2 max), respectively) and (13)CO(2) production, and muscle glycogen oxidation was estimated by subtracting plasma glucose oxidation from total carbohydrate oxidation. Consistent data from the literature suggest that this small dose of exogenous glucose does not modify muscle glycogen oxidation and has little effect, if any, on plasma glucose oxidation. The percent contributions of plasma glucose and muscle glycogen oxidation to the energy yield at 48% Vo(2 max) [15.1% (SD 3.8) and 45.9% (SD 5.8)] and at 76% Vo(2 max) [15.4% (SD 3.6) and 59.8% (SD 9.2)] were well in line with data previously reported for similar work loads and exercise durations using conventional tracer techniques. The significant reduction in glycogen concentration measured from pre- and postexercise vastus lateralis muscle biopsies paralleled muscle glycogen oxidation calculated using the tracer technique and was larger at 76% than at 48% Vo(2 max). However, the correlation coefficients between these two estimates of muscle glycogen utilization were not different from zero at each of the two work loads. The simplified tracer technique used in the present experiment appears to be a valid alternative approach to the traditional tracer techniques for computing plasma glucose and muscle glycogen oxidation during prolonged exercise. PMID- 17272413 TI - The significance of variable passive compliance in smooth muscle. PMID- 17272415 TI - Stimulating motor wisdom. PMID- 17272416 TI - Point: Medullary pacemaker neurons are essential for both eupnea and gasping in mammals. PMID- 17272417 TI - Growth and maturation of the spine from birth to adolescence. PMID- 17272418 TI - Growth considerations of the immature spine. PMID- 17272419 TI - Maturity indicators in spinal deformity. PMID- 17272420 TI - Natural history of early onset scoliosis. PMID- 17272421 TI - Medical and congenital comorbidities associated with spinal deformities in the immature spine. PMID- 17272422 TI - Management themes in early onset scoliosis. PMID- 17272423 TI - Management of juvenile idiopathic scoliosis. PMID- 17272424 TI - Formation errors of the vertebral column. PMID- 17272425 TI - Management themes in congenital scoliosis. PMID- 17272426 TI - Infection and tumors of the spine in children. PMID- 17272427 TI - Pediatric spine trauma. PMID- 17272428 TI - Thoracic insufficiency syndrome and exotic scoliosis. PMID- 17272429 TI - The immature spine in type-1 neurofibromatosis. PMID- 17272430 TI - Spinal deformity secondary to impaired neurologic control. PMID- 17272431 TI - Spine deformity in spinal muscular atrophy. PMID- 17272432 TI - Scoliosis in patients with Duchenne muscular dystrophy. PMID- 17272433 TI - Early onset scoliosis: future directions. PMID- 17272434 TI - The reverse total shoulder prosthesis. The new kid on the block. PMID- 17272435 TI - A prospective, randomized study of computer-assisted and conventional total knee arthroplasty. Three-dimensional evaluation of implant alignment and rotation. AB - BACKGROUND: Despite the use of modern instruments in total knee arthroplasty, component malalignment remains a problem. Whether a computer-assisted implantation technique can improve the accuracy of the spatial positioning of an implant is a matter of debate. The objective of this study was to determine whether computer-assisted total knee arthroplasty is superior to the conventional surgical method with regard to the precision of implant positioning. METHODS: The spatial positioning of the implant in sixty total knee arthroplasties (thirty-two imageless computer-assisted and twenty-eight conventional implantations) was determined three-dimensionally with use of computed tomographic measurement, which allowed derotation and full extension of the knee in order to avoid projection-related imaging errors. RESULTS: The overall mechanical axis showed a range of between 4.8 degrees of valgus and 6.6 degrees of varus alignment in the frontal plane for conventionally implanted arthroplasty components compared with a significantly smaller range of between 2.9 degrees of valgus and 3.1 degrees of varus alignment for computer-assisted implantations (p = 0.004). In relation to the tibial implant, the mean deviation (and standard deviation) from the mechanical axis was 2.0 degrees +/- 1.7 degrees for the conventional surgical method and 1.4 degrees +/- 0.9 degrees for the navigated implantation. The rotational deviation from the referenced axis of the femoral component was between 3.3 degrees of internal rotation and 5.0 degrees of external rotation for the conventional implantation method, with a mean deviation of 0.1 degrees +/- 2.2 degrees. Femoral components implanted with computer assistance showed a deviation of between 4.7 degrees of internal rotation and 2.2 degrees of external rotation, with a mean deviation of 0.3 degrees +/- 1.4 degrees. CONCLUSIONS: In this study, with our technique of filtering out projection-related imaging errors, computer-assisted implantation of total knee replacements improved the frontal and sagittal alignment of the femoral component but not of the tibial component. We found that the rotational alignment of the component was not improved through navigation by solely referencing to the epicondylar axis for the femur and the tuberosity for the tibia. PMID- 17272436 TI - Arthroscopic compared with open repairs for recurrent anterior shoulder instability. A systematic review and meta-analysis of the literature. AB - BACKGROUND: Both arthroscopic and open surgical repairs are utilized for the management of anterior glenohumeral instability. To determine the evidence supporting the relative effectiveness of these two approaches, we conducted a rigorous and comprehensive analysis of all reports comparing arthroscopic and open repairs. METHODS: A systematic analysis of eighteen published or presented studies was performed to determine if there were significant differences between the two approaches with regard to recurrence (recurrent dislocation, subluxation, and/or apprehension and/or a reoperation for instability), return to work and/or sports, and Rowe scores. We also performed subgroup analysis to determine if the quality of the study or the arthroscopic technique influenced the results. RESULTS: We identified four randomized controlled trials, ten controlled clinical trials, and four other comparative studies. Results were influenced both by the quality of the study and by the arthroscopic technique. Meta-analysis revealed that, compared with open methods, arthroscopic repairs were associated with significantly higher risks of recurrent instability (p < 0.00001, relative risk = 2.37, 95% confidence interval = 1.66 to 3.38), recurrent dislocation (p < 0.0001, relative risk = 2.74, 95% confidence interval = 1.75 to 4.28), and a reoperation (p = 0.002, relative risk = 2.32, 95% confidence interval = 1.35 to 3.99). When considered alone, arthroscopic suture anchor techniques were associated with significantly higher risks of recurrent instability (p = 0.01, relative risk = 2.25, 95% confidence interval = 1.21 to 4.17) and recurrent dislocation (p = 0.004, relative risk = 2.57, 95% confidence interval = 1.35 to 4.92) than were open methods. Arthroscopic approaches were also less effective than open methods with regard to enabling patients to return to work and/or sports (p = 0.03, relative risk = 0.87, 95% confidence interval = 0.77 to 0.99). On the other hand, analysis of the randomized clinical trials indicated that arthroscopic repairs were associated with higher Rowe scores (p = 0.002, standardized mean difference = 0.43, 95% confidence interval = 0.16 to 0.70) than were open methods. Similarly, analysis of the arthroscopic suture anchor techniques alone showed the Rowe scores to be higher (p = 0.04, standardized mean difference = 0.29, 95% confidence interval = 0.01 to 0.56) than those associated with open methods. CONCLUSIONS: The available evidence indicates that arthroscopic approaches are not as effective as open approaches in preventing recurrent instability or enabling patients to return to work. Arthroscopic approaches resulted in better function as reflected by the Rowe scores in the randomized clinical trials. The study design and the arthroscopic technique had substantial effects on the results of the analysis. PMID- 17272437 TI - Treatment of chronic radial epicondylitis with botulinum toxin A. A double-blind, placebo-controlled, randomized multicenter study. AB - BACKGROUND: Radial epicondylitis (tennis elbow) is the most frequent type of myotendinosis. Patients can experience substantial loss of function, especially when this condition becomes chronic. A successful therapy has not yet been established. A preliminary study of injections of botulinum toxin A in patients with chronic epicondylitis has shown promising results. METHODS: In the present prospective, controlled, double-blinded clinical trial, 130 patients were examined at sixteen study centers. A single injection of botulinum toxin A into the painful origin of the forearm extensor muscles was performed. Follow-up examinations were performed at two, six, twelve, and eighteen weeks. Clinical findings were documented with use of a new clinical pain score and with a visual analogue scale. A global assessment of the result of treatment was also provided by the patient and the attending doctor. Strength of extension of the third finger and the wrist was evaluated with use of the Brunner method, and grip strength (fist closure strength) was measured with a vigorimeter. RESULTS: The group treated with botulinum toxin A was found to have a significant improvement in the clinical findings, compared with those in the placebo group, as early as the second week after injection (p = 0.003). Subjective general assessment also showed improvement in that group, compared with the placebo group, at six weeks (p = 0.001) and at the time of the final examination (at eighteen weeks) (p = 0.001). There was a consistent increase in fist closure strength in both the group treated with botulinum toxin A and the control group, but there was no significant difference between groups. As was expected as a side effect, extension of the third finger was observed to be significantly weakened at two weeks but this complication had completely resolved at eighteen weeks. CONCLUSIONS: We concluded that local injection of botulinum toxin A is a beneficial treatment for radial epicondylitis (tennis elbow). The treatment can be performed in an outpatient setting and does not impair the patient's ability to work. PMID- 17272438 TI - Navigated total knee replacement. A meta-analysis. AB - BACKGROUND: Proponents of navigated knee arthroplasty stress its potential to increase the precision of component placement. We conducted a systematic review and meta-analysis to substantiate the validity and relevance of this contention. METHODS: We searched major medical and publishers' databases for randomized trials and any other studies comparing navigated with conventional knee arthroplasty. Major periodicals were searched manually. We made no restrictions for types of studies or language. Methodological features were rated independently by two reviewers. After testing for publication bias and heterogeneity was done, the data were aggregated by random-effects modeling. We estimated the weighted mean differences of mechanical limb axes and functional scales and the risk ratios of deviations from the straight axis with 95% confidence intervals. RESULTS: We included thirty-three studies (eleven randomized trials) of varying methodological quality involving 3423 patients with a mean age (and standard deviation) of 67.3 +/- 4.1 years (62.6% were women, and 83.7% had primary osteoarthritis). The mean preoperative deviation from the mechanical axis was 2.3 degrees +/- 5.1 degrees. There was no evidence of publication bias, but there was strong statistical heterogeneity. The alignment of the mechanical axes did not differ between the navigated and conventional surgery group (weighted mean difference, 0.2 degrees; 95% confidence interval, 0.2 degrees to 0.5 degrees). Patients managed with navigated surgery had a lower risk of malalignment at critical thresholds of >3 degrees (risk ratio, 0.79; 95% confidence interval, 0.71 to 0.87) and >2 degrees (risk ratio, 0.76; 95% confidence interval, 0.71 to 0.82). No conclusive inferences could be drawn on functional outcomes or complication rates. Navigation lengthened the mean duration of surgery by 23%. CONCLUSIONS: Navigated knee replacement provides few advantages over conventional surgery on the basis of radiographic end points. Its clinical benefits are unclear and remain to be defined on a larger scale. PMID- 17272439 TI - Intraoperative red blood-cell salvage in revision hip surgery. A case-matched study. AB - BACKGROUND: Revision hip arthroplasty is commonly associated with substantial blood loss and the subsequent need for transfusion. This leads to an increased risk of blood-borne infection and hemolytic reactions. The purpose of this study was to demonstrate whether the use of intraoperative red blood-cell salvage in revision hip arthroplasty reduces the overall rate of allogeneic transfusion. METHODS: Forty-seven patients who had undergone revision hip arthroplasty with the use of intraoperative cell salvage were identified. A computer database was used to individually match these patients, for age, sex, and eleven operative variables, to control patients who had undergone revision hip arthroplasty in the same unit without intraoperative cell salvage. Data gathered included the total allogeneic transfusion requirement for each patient, preoperative and postoperative hemoglobin levels, and operative time. RESULTS: The total allogeneic transfusion requirement was significantly lower in the group that had intraoperative cell salvage than in the control group (median, 2 compared with 6 U of packed red blood cells, p = 0.0006), with a median reduction in allogeneic transfusion of 4 U. There was no significant difference in preoperative or postoperative hemoglobin levels between the groups. CONCLUSIONS: The use of intraoperative cell salvage significantly lowered the allogeneic transfusion requirement, which can lead to substantial cost savings. To our knowledge, this is the first study in which the use of intraoperative red blood-cell salvage in revision hip arthroplasty was evaluated by matching patients on the basis of age, sex, and operative variables. PMID- 17272440 TI - Extraperiosteal plating of pronation-abduction ankle fractures. AB - BACKGROUND: Pronation-abduction ankle fractures frequently are associated with substantial lateral comminution and have been reported to be associated with the highest rates of nonunion among indirect ankle fractures. The purpose of the present study was to report the technique for and outcomes of extraperiosteal plating in a series of patients with pronation-abduction ankle fractures. METHODS: Thirty-one consecutive patients with an unstable comminuted pronation abduction ankle fracture were managed with extraperiosteal plating of the fibular fracture. The average age of the patients was forty-four years. There were nineteen bimalleolar and twelve lateral malleolar fractures with an associated deltoid ligament injury. No attempt to reduce the comminuted fragments was made as this area was spanned by the plate. The patients were evaluated functionally (with use of the American Orthopaedic Foot and Ankle Society score), radiographically, and clinically (with range-of-motion testing). RESULTS: Immediate postoperative and final follow-up radiographs showed that all patients had a well-aligned ankle mortise on the fractured side as compared with the normal side on the basis of standardized measurements. All fractures healed without displacement. At a minimum of two years after the injury, the average American Orthopaedic Foot and Ankle Society score (available for twenty-one patients) was 82. The range of motion averaged 13 degrees of dorsiflexion and 31 degrees of plantar flexion, with one patient not achieving dorsiflexion to neutral. There were no deep infections, and one patient had an area of superficial skin breakdown that healed without operative intervention. CONCLUSIONS: Extraperiosteal plating of pronation-abduction ankle fractures is an effective method of stabilization that leads to predictable union of the fibular fracture. The results of this procedure are at least as good as those of other techniques of open reduction and internal fixation of the ankle, although specific results for pronation-abduction injuries have not been previously reported, to our knowledge. PMID- 17272441 TI - Manipulation after total knee arthroplasty. AB - BACKGROUND: Following total knee arthroplasty, some patients who fail to achieve >90 degrees of flexion in the early perioperative period may be considered candidates for manipulation of the knee under anesthesia. The purpose of this study was to assess the outcomes of manipulation following total knee arthroplasty. METHODS: One hundred and thirteen knees in ninety patients underwent manipulation for postoperative flexion of < or =90 degrees at a mean of ten weeks after surgery. Flexion was measured with a goniometer prior to total knee arthroplasty, at the conclusion of the operative procedure, before manipulation, immediately after manipulation, at six months, and at one, three, and five years postoperatively. RESULTS: Eighty-one (90%) of the ninety patients achieved improvement of ultimate knee flexion following manipulation. The average flexion was 102 degrees prior to total knee arthroplasty, 111 degrees following skin closure, and 70 degrees before manipulation. The average improvement in flexion from the measurement made before manipulation to that recorded at the five-year follow-up was 35 degrees (p < 0.0001, paired t test). There was no significant difference in the mean improvement in flexion when patients who had manipulation within twelve weeks postoperatively were compared with those who had manipulation more than twelve weeks postoperatively. Patients who eventually underwent manipulation had significantly lower preoperative Knee Society pain scores (more pain) than those who had not had manipulation (p = 0.0027). CONCLUSIONS: Manipulation generally increases ultimate flexion following total knee arthroplasty. Patients with severe preoperative pain are more likely to require manipulation. PMID- 17272442 TI - Antibiotic dosing before primary hip and knee replacement as a pay-for performance measure. AB - BACKGROUND: There is a trend toward linking the reimbursement for health care services to clinical outcome. One such pay-for-performance proposal that affects orthopaedic surgeons is linking reimbursement for hip and knee replacements to measures such as the percentage of patients receiving antibiotics before surgery. We analyzed the risk factors associated with failing to optimally administer preoperative antibiotics before primary hip and knee arthroplasty. METHODS: Data on 988 elective primary total hip and knee replacements done at one institution were collected. Multivariate analysis was performed to determine clinical factors associated with administration of antibiotics outside the recommended window (within one hour before the incision). RESULTS: Thirteen percent of the patients did not receive optimal antibiotic therapy (within the one-hour window prior to the elective arthroplasty). Five patients (0.5%) received no documented preoperative antibiotics. Patients undergoing total hip arthroplasty were more likely to receive antibiotics outside the one-hour window than were patients undergoing total knee arthroplasty. Longer induction times were associated with administration of antibiotics outside the one-hour window. Certain individual surgeons and anesthesiologists were more likely to administer antibiotics on time. The anesthesiologist effect was more significant than the surgeon effect. CONCLUSIONS: Approximately 13% of the patients did not receive optimal antibiotic therapy before total hip and knee replacement. Surgeons can improve their performance score for this measure by focusing antibiotic strategies on patients receiving a hip replacement and on complex cases, by developing systems for antibiotic dosing with the anesthesia team, and by improving documentation. PMID- 17272443 TI - The use of the reverse shoulder prosthesis for the treatment of failed hemiarthroplasty for proximal humeral fracture. AB - BACKGROUND: Humeral hemiarthroplasty is an established treatment for patients with selected fractures of the proximal part of the humerus. However, a subset of patients have development of glenoid arthritis and rotator cuff deficiency due to tuberosity failure. To date, there has been no reliable salvage procedure for this problem. METHODS: Over a period of five years, twenty-nine patients (twenty five women and four men) with a mean age of sixty-nine years (range, forty-two to eighty years) were managed with removal of a hemiarthroplasty prosthesis and revision with a Reverse Shoulder Prosthesis alone or in combination with a proximal humeral allograft. Patients were followed clinically and radiographically for an average of thirty-five months. All patients were evaluated with use of the American Shoulder and Elbow Surgeons score; the Simple Shoulder Test; range-of-motion measurements, including abduction, forward flexion, and external rotation; and a rating scale for overall satisfaction with the outcome of the surgery. Patients were assessed preoperatively and at all follow-up points beginning at three months postoperatively. RESULTS: The average total American Shoulder and Elbow Surgeons score improved from 22.3 preoperatively to 52.1 at the time of the last follow-up (p < 0.001). The average American Shoulder and Elbow Surgeons pain score improved from 12.2 to 34.4 (p < 0.001), and the average American Shoulder and Elbow Surgeons function score improved from 10.1 to 17.7 (p = 0.058). The average Simple Shoulder Test score improved from 0.9 to 2.6 (p = 0.004). Forward flexion improved from 38.1 degrees to 72.7 degrees (p < 0.001), and abduction improved from 34.1 degrees to 70.4 degrees (p < 0.001). The overall complication rate was 28% (eight of twenty nine). At the time of the latest follow-up, sixteen patients rated the outcome as good or excellent, seven rated it as satisfactory, and six were dissatisfied. Four of the six patients who were dissatisfied had been managed with a Reverse Shoulder Prosthesis alone. CONCLUSIONS: The Reverse Shoulder Prosthesis offers a salvage-type solution to the problem of failed hemiarthroplasty due to glenoid arthritis and rotator cuff deficiency following tuberosity failure. The early results reported here are promising. In cases of severe proximal humeral bone deficiency, augmentation of the Reverse Shoulder Prosthesis with a proximal humeral allograft may improve patient satisfaction. PMID- 17272444 TI - Effective osteoporosis education in the outpatient orthopaedic setting. AB - BACKGROUND: The orthopaedic surgeon may be the first medical specialist to interact with a patient with clinically important osteoporosis, providing an opportunity to educate that patient about this disease. The purpose of the present study was to investigate whether patients could be effectively educated with regard to osteoporosis and lifestyle modification during their outpatient visits to an orthopaedic surgeon's office. METHODS: Eighty female patients ranging from fifteen to seventy-three years of age completed an eleven-question quiz that included items regarding their knowledge of osteoporosis, calcium intake, menopausal status, exercise, smoking, and whether or not they had had a bone mineral density scan. The quiz was completed during a visit to an outpatient sports medicine/general orthopaedic clinic. After the quiz, an educational intervention was performed by providing the patients with an informational handout. The patients were followed at an average interval of six months and were reassessed either in the office or over the telephone with use of the same quiz to evaluate increases in knowledge and modification of lifestyle. RESULTS: Fifty four premenopausal and twenty-six postmenopausal patients were available for follow-up. The premenopausal and postmenopausal groups differed at the beginning of the study, with premenopausal patients having a higher daily calcium intake (p = 0.008) and a better ability to define osteoporosis (p = 0.004) and postmenopausal patients having a higher rate of having had a prior bone mineral density scan (p < 0.001). In response to the educational intervention, significant improvements were seen in terms of the patients' ability to define osteoporosis (p = 0.004), the ability to identify being female as a major risk factor (p < 0.001), and the understanding that females should begin adequate calcium intake at a young age (p < 0.001). Significant increases in daily calcium intake (p < 0.001) and exercise level also occurred (p < 0.003). The postmenopausal group demonstrated a less robust response to the educational intervention. CONCLUSIONS: The outpatient orthopaedic sports medicine office setting represents a prime opportunity for education regarding osteoporosis prevention and lifestyle modification that can be performed in an inexpensive fashion and that can be easily replicated in most offices both in the community and in academic settings. PMID- 17272445 TI - Testing of a new one-stage bone-transport surgical procedure exploiting the periosteum for the repair of long-bone defects. AB - BACKGROUND: A recently proposed one-stage bone-transport surgical procedure exploits the intrinsic osteogenic potential of the periosteum while providing mechanical stability through intramedullary nailing. The objective of this study was to assess the efficacy of this technique to bridge massive long-bone defects in a single stage. METHODS: With use of an ovine femoral model, an in situ periosteal sleeve was elevated circumferentially from healthy diaphyseal bone, which was osteotomized and transported over an intramedullary nail into a 2.54-cm (1-in) critical-sized diaphyseal defect. The defect-bridging and bone regenerating capacity of the procedure were tested in five groups of seven animals each, which were defined by the absence (Group 1; control) or presence of the periosteal sleeve alone (Group 2), bone graft within the periosteal sleeve (Groups 3 and 5), as well as retention of adherent, vascularized cortical bone chips on the periosteal sleeve with or without bone graft (Groups 4 and 5). The efficacy of the procedure was assessed qualitatively and quantitatively. RESULTS: At sixteen weeks, osseous bridging of the defect was observed in all twenty-eight experimental sheep in which the periosteal sleeve was retained; the defect persisted in the remaining seven control sheep. Among the experimental groups 2 through 5, significant differences were observed in the density of the regenerated bone tissue; the two groups in which vascularized bone chips adhered to the inner surface of the periosteal sleeve (Groups 4 and 5) showed a higher mean bone density in the defect zone (p < 0.02) than did the other groups. In these two groups with the highest bone density, the addition of bone graft was associated with a significantly lower callus density than that observed without bone graft (p < 0.05). The volume of regenerate bone (p < 0.02) was significantly greater in the groups in which the periosteal sleeve was retained than it was in the control group. Among the experimental groups (groups 2 through 5), however, with the numbers studied, no significant differences in the volume of regenerate bone could be attributed to the inclusion of bone graft within the sleeve or to vascularized bone chips remaining adherent to the periosteum. CONCLUSIONS: The novel surgical procedure was shown to be effective in bridging a critical-sized defect in an ovine femoral model. Vascularized bone chips adherent to the inner surface of the periosteal sleeve, without the addition of morselized cancellous bone graft within the sleeve, provide not only a comparable volume of regenerate bone and composite tissue (callus and bone) but also a superior density of regenerate bone compared with that after the addition of bone graft. PMID- 17272446 TI - Variability in rates of arthrodesis procedures for patients with cervical spine injuries with and without associated spinal cord injury. AB - BACKGROUND: Cervical spine injury, with or without spinal cord injury, is an important cause of morbidity and mortality in the United States. While substantial regional variation has been shown in per capita rates of elective cervical spine surgery, similar data regarding arthrodesis rates for traumatic cervical injury have not been reported, to our knowledge. We assessed the rates of cervical spinal arthrodesis for patients who had a cervical spine injury with or without an associated spinal cord injury. METHODS: The data for the present study came from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1998 to 2002. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with a cervical vertebral fracture or dislocation with or without an associated spinal cord injury. Hospitals were grouped according to their teaching status, location (urban or rural), and volume of cervical spine injury patients. The rates of spinal arthrodesis and halo/tong placement were compared for patients within each diagnostic category. RESULTS: Twenty-eight thousand, five hundred and eighteen patients with a cervical spine injury were analyzed. Spinal arthrodesis was performed for 16.5% of patients who had a cervical fracture without an associated spinal cord injury, for 50.4% of patients who had a cervical spine fracture with an associated spinal cord injury, and for 44.1% of patients who had a cervical dislocation. With the numbers available, the rates of arthrodesis for patients who had a fracture without a spinal cord injury and for patients who had a cervical dislocation were not significantly different between high and low-volume centers, although the rate for patients who had a cervical fracture with a spinal cord injury was significantly higher at high-volume hospitals. The rates of arthrodesis did not vary significantly between urban teaching and nonteaching hospitals, with the numbers available, for patients in any of the three diagnostic categories. Individual hospitals had a threefold to fivefold variation in the arthrodesis rate for patients with a cervical spine injury, depending on the diagnostic category. CONCLUSIONS: The present study demonstrated substantial differences in the rate of arthrodesis for patients with cervical spine trauma, depending on the diagnostic category. The variations in the rates of arthrodesis within diagnostic categories appear to be lower than the previously reported variation in the rates of elective cervical spine procedures. PMID- 17272447 TI - Analysis of outcomes for surgically treated hip fractures in patients undergoing chronic hemodialysis. AB - BACKGROUND: Hip fractures in patients with end-stage renal disease are associated with frequent complications. This study analyzed clinical outcomes for patients on chronic hemodialysis who sustained hip fractures and were treated with a variety of fracture repair methods. METHODS: Twenty-nine patients with thirty-two hip fractures were analyzed in three groups. Group 1 consisted of eleven hips in eleven patients with an intertrochanteric fracture that was treated with internal fixation; Group 2, thirteen hips in ten patients with a femoral neck fracture that was treated with screw fixation; and Group 3, eight hips in eight patients with a femoral neck fracture that was treated with hemiarthroplasty. The outcomes and early and late complications were recorded for each group. Survivorship analysis was performed, and the mortality and complication rates for the groups were compared. RESULTS: In Group 1, eight complications occurred in six hips and nonunion developed in five hips. In Group 2, sixteen complications developed in eleven hips. Union was achieved in two of the thirteen hips, nine hips had nonunion, and two hips had osteonecrosis develop. In Group 3, only one hip had early complications, there were no late complications, and three patients died. The mean duration of follow-up was twenty-three months, and the overall mortality rate was 45%. There were no significant differences among the groups with respect to the cumulative survival proportions. Regression analysis of age, sex, and total hemodialysis duration in relation to mortality risk revealed that only age had a significant influence on mortality (p = 0.019). CONCLUSIONS: Surgical treatment of hip fractures in patients with end-stage renal disease who are on chronic hemodialysis is associated with frequent complications and a high mortality rate. Osteosynthesis is an acceptable option for treating intertrochanteric fractures and nondisplaced femoral neck fractures, but displaced femoral neck fractures should be treated with hemiarthroplasty. PMID- 17272448 TI - Distribution of posterior tibial displacement in knees with posterior cruciate ligament tears. AB - BACKGROUND: While stress radiography has been used to objectively determine the limits of posterior tibial displacement in knees with posterior cruciate ligament tears, the magnitude and distribution of posterior tibial translation has not been defined in a large population of patients with this injury. METHODS: A retrospective diagnostic study of 1041 consecutive patients with posterior cruciate ligament tears was done. Posterior tibial displacement values that were obtained with use of instrumented stress radiography with the knee held in 90 degrees of flexion in the Telos device were evaluated and compared with the values from relevant cadaveric dissection studies. RESULTS: The mean amount of posterior tibial displacement on stress radiographs was -11.58 +/- 4.31 mm (range, -5 to -30 mm). There was a displacement peak in the range of -9 to -12 mm, with 37.9% of patients exhibiting posterior laxity within this range. Traffic related injuries were associated with significantly greater displacement values than were sports-related injuries (p < 0.001). Grade-I or II instability (12 mm of posterior tibial displacement) occurred in association with 68.7% of the sports-related injuries, compared with 54.1% of the traffic-related injuries (p < 0.001). The mean amount of posterior tibial displacement on the intact side was 1.31 +/- 1.85 mm (range, -6 to 4 mm). CONCLUSIONS: Instrumented stress radiography is a useful testing method for objectively determining the amount of posterior tibial displacement of the knee in adults with a posterior cruciate ligament injury. Absolute posterior tibial displacement in excess of 8 mm is indicative of complete insufficiency of the posterior cruciate ligament. With tibial displacement exceeding 12 mm, additional injury of secondary restraining structures should be considered. We recommend the use of stress radiography to grade and classify posterior knee laxity. PMID- 17272449 TI - Results of metal-on-metal hybrid hip resurfacing for Crowe type-I and II developmental dysplasia. AB - BACKGROUND: Modern hip resurfacing implants may increase stability and preserve more bone than conventional total hip arthroplasty. The purpose of this retrospective study was to analyze the mid-term results in a consecutive series of middle-aged patients with developmental dysplasia of the hip treated with hybrid resurfacing joint arthroplasty. METHODS: Metal-on-metal hip resurfacing was performed in fifty-one patients (fifty-nine hips), forty-two of whom were female and nine of whom were male. The average age at the time of surgery was 43.7 years. Radiographic and clinical data were collected at six weeks, at three months, and at yearly follow-up visits. Seven hips had Crowe type-II developmental dysplasia of the hip and fifty-two had type-I. RESULTS: The follow up period ranged from 4.2 to 9.5 years (average, 6.0 years). Initial stability was achieved in all but three hips. The clinical outcomes, as rated with the University of California at Los Angeles (UCLA) hip score, improved significantly compared with the preoperative ratings. On the average, the pain rating improved from 3.2 to 9.3 points; the score for walking, from 6.0 to 9.7 points; the score for function, from 5.7 to 9.6 points; and the score for activity, from 4.6 to 7.3 points (all p = 0.0001). The mean Short Form-12 (SF-12) mental score increased from 46.6 to 53.5 points, and the mean SF-12 physical score increased from 31.7 to 51.4 points (both p < 0.0001). The mean postoperative Harris hip score was 92.5 points. On the average, the range of flexion improved from 106 degrees to 129.6 degrees ; the abduction-adduction arc, from 41.9 degrees to 76.9 degrees ; and the rotation arc in extension, from 32.1 degrees to 84.8 degrees (all p = 0.0001). Four patients delivered a total of six healthy babies since the time of implantation of the prosthesis. Radiographic analysis showed a decrease in the mean body weight lever arm from 118.5 mm preoperatively to 103.9 mm postoperatively (p = 0.007). There were five femoral failures requiring conversion to a total hip arthroplasty. One hip showed a radiolucency around the metaphyseal femoral stem. There were no complete acetabular radiolucencies, and all sockets remained well fixed. CONCLUSIONS: The mid-term results of metal-on metal resurfacing in patients with Crowe type-I or II developmental dysplasia of the hip were disappointing with respect to the durability of the femoral component. However, the fixation of the porous-coated acetabular components without adjuvant fixation was excellent despite incomplete lateral acetabular coverage of the socket. More rigorous patient selection and especially meticulous bone preparation are essential to minimize femoral neck fractures and loosening after this procedure. PMID- 17272452 TI - Failure analysis of a ceramic bearing acetabular component. AB - BACKGROUND: Alternative bearings have been explored in an attempt to improve the longevity of total hip prostheses. A Food and Drug Administration (FDA)-approved clinical study of a nonmodular acetabular component consisting of a porous metal shell, compression-molded polyethylene, and a ceramic liner inlay was discontinued following reports of early failures. METHODS: Between October 1999 and January 2003, 429 patients were enrolled in a prospective study to evaluate a cementless ceramic-on-ceramic total hip arthroplasty design (Hedrocel ceramic bearing cup; Implex, Allendale, New Jersey). Two hundred and eighty-two patients (315 hips) were treated with the experimental acetabular implant and 147 patients (157 hips) were treated with an acetabular implant that consisted of the same porous shell but an allpolyethylene liner. Clinical data including a Harris hip score and responses to the Short Form-12 (SF-12) health survey were collected preoperatively and at twelve and twenty-four months postoperatively. Serial radiographs were made preoperatively; at six weeks, three months, six months, and twelve months postoperatively; and annually thereafter. Retrieval analysis was performed on all failed explanted components. Failure was defined as fracture or displacement of the ceramic liner out of the acetabular component. In addition, biomechanical testing was performed on unimplanted acetabular components and mechanically altered cups in an effort to recreate the mechanisms of failure. Finite element analysis was used to estimate stress and strain within the ceramic liner under extreme physiologic loading conditions. RESULTS: The ceramic liner failed in fourteen of the 315 experimental acetabular components; all of the failures were at the ceramic-polyethylene interface. Patients with a body weight of >91 kg had a 4.76 times greater odds of the ceramic liner failing than those who weighed < or =91 kg. Retrieval analysis demonstrated stripe and rim wear with evidence of adhesive wear, indicating a potentially high-friction interaction at the articulation. Finite element analysis demonstrated that the forces on the ceramic liner in cups subjected to extreme loading conditions were insufficient to cause fracture. Biomechanical testing was unable to reproduce an initial ceramic liner displacement in vitro; however, when the ceramic liner was forcibly displaced prior to biomechanical testing, complete displacement and eventual fracture of the ceramic liner resulted. CONCLUSIONS: We hypothesized that the combination of a high patient body weight, an extensive range of motion, and subluxation of the femoral head led to high friction at the articulation between the femoral head and the rim of the liner, which initiated displacement of the ceramic liner. Subsequent normal gait led to further displacement of the liner in all of the fourteen failed components and eventually to ceramic fracture in twelve of the fourteen components. PMID- 17272451 TI - Electromyographic and magnetic resonance imaging to predict lumbar stenosis, low back pain, and no back symptoms. AB - BACKGROUND: Magnetic resonance imaging is commonly used to diagnose lumbar spinal stenosis. Some persons without symptoms have a small lumbar spinal canal. Electrodiagnosis has been used to diagnose spinal stenosis for over sixty years, but we are aware of no masked, controlled trials of the use of electrodiagnosis for that purpose. This study was performed to evaluate the relationships of magnetic resonance imaging measures and electrodiagnostic data with the clinical syndrome of spinal stenosis. METHODS: One hundred and fifty persons between the ages of fifty-five and eighty years old, including asymptomatic volunteers and persons referred for lumbar magnetic resonance imaging, underwent clinical examination, electrodiagnosis, and magnetic resonance imaging. Subjects were excluded if they had neuromuscular disease, sacral cancer, or inadequate test results, which left 126 subjects for the final analysis. The final cohort was divided into three groups--no back pain, mechanical back pain, and clinical spinal stenosis--on the basis of the impression of the examining physician, for whom the results of the magnetic resonance imaging and electrodiagnostic testing were masked. A spine surgeon also reviewed both the imaging and clinical examination data. RESULTS: The examining physician's diagnosis of clinical spinal stenosis was significantly related to the neurological findings on examination (p < 0.05) and to the spine surgeon's diagnosis (p < 0.001). The diagnosis of clinical spinal stenosis was also significantly related to the presence of fibrillations on electrodiagnostic testing (p < or = 0.003), the minimum anteroposterior diameter of the spinal canal on the magnetic resonance images (p = 0.016), and the average of the two smallest spinal canal diameters (p = 0.008) on the images. Measurements on magnetic resonance imaging did not differentiate subjects with clinical spinal stenosis from controls better than chance, whereas paraspinal mapping electrodiagnosis scores did. CONCLUSIONS: This prospective, controlled, masked study of electrodiagnosis and magnetic resonance imaging for older subjects showed that imaging does not differentiate symptomatic from asymptomatic persons, whereas electrodiagnosis does. We believe that radiographic findings alone are insufficient to justify treatment for spinal stenosis. PMID- 17272450 TI - Hematopoietic stem-cell contribution to ectopic skeletogenesis. AB - BACKGROUND: Fibrodysplasia ossificans progressiva is a rare genetic disorder of ectopic skeletogenesis associated with dysregulation of bone morphogenetic protein (BMP) signaling. Hematopoietic cells have been implicated in the ectopic skeletogenesis of fibrodysplasia ossificans progressiva, and their replacement has been postulated as a possible cure. However, the definitive contribution of hematopoietic cells to the pathogenesis of ectopic skeletogenesis remains obscure. METHODS: We employed both careful clinical observation and in vivo murine transplantation studies to more precisely determine the contribution of hematopoietic cells to ectopic skeletogenesis. We identified a patient with fibrodysplasia ossificans progressiva who had undergone bone marrow transplantation for the treatment of intercurrent aplastic anemia twenty-five years earlier and investigated whether the clinical course of the fibrodysplasia ossificans progressiva had been influenced by bone marrow replacement or immunosuppression, or both. In complementary studies, we transplanted hematopoietic stem cells from constitutively expressing LacZ transgenic mice to identify the contribution of hematopoietic cells to BMP4-induced heterotopic ossification, a histopathologic model of fibrodysplasia ossificans progressiva. RESULTS: We found that replacement of hematopoietic cells was not sufficient to prevent ectopic skeletogenesis in the patient with fibrodysplasia ossificans progressiva but pharmacologic suppression of the apparently normal donor immune system following transplantation in the new host modulated the activity of the fibrodysplasia ossificans progressiva and diminished the expression of skeletal ectopia. In complementary murine transplantation studies, we found that cells of hematopoietic origin contributed to the early inflammatory and late marrow repopulating stages of BMP4-induced heterotopic ossification but were not represented in the fibroproliferative, chondrogenic, or osteogenic stages of heterotopic ossification. Interestingly, both recombinant human BMP4 induction in an animal model and the dysregulated BMP signaling pathway in a patient with fibrodysplasia ossificans progressiva were sufficient to recruit at least two populations of cells, one of hematopoietic origin and at least one of non hematopoietic origin, that contribute to the formation of an ectopic skeleton. CONCLUSIONS: Taken together, these findings demonstrate that bone marrow transplantation did not cure fibrodysplasia ossificans progressiva in the patient in this study, most likely because the hematopoietic cell population is not the site, or at least not the dominant site, of the intrinsic dysregulation of the BMP signaling pathway in fibrodysplasia ossificans progressiva. However, following transplantation of bone marrow from a presumably normal donor, immunosuppression of the immune system appeared to ameliorate activation of ectopic skeletogenesis in a genetically susceptible host. Thus, cells of hematopoietic origin may contribute to the formation of an ectopic skeleton, although they are not sufficient to initiate the process alone. PMID- 17272453 TI - Prevalence of cervical spine stenosis. Anatomic study in cadavers. AB - BACKGROUND: The sagittal diameter of the cervical spinal canal is of clinical importance in traumatic, degenerative, and inflammatory conditions. A small canal diameter has been associated with an increased risk of injury; however, there is a lack of reliable normative data on spinal canal diameters in different age groups in the United States population. The purpose of this study was to use direct measurement of skeletal specimens to determine the spectrum of the sagittal diameters of the cervical spinal canal, the frequency of cervical stenosis in the general population, and the prevalence of cervical stenosis for different age groups, races, and sexes. METHODS: Four hundred and sixty-nine adult skeletal specimens of the cervical spine were obtained from the Hamann-Todd Collection in the Cleveland Museum of Natural History. With use of digital calipers, the distance from the posteriormost aspect of the vertebral body to the anteriormost aspect of the spinolaminar structure was measured and recorded for each specimen at every level from C3 to C7. Cervical stenosis was defined as a canal diameter of <12 mm. We analyzed the direct measurements and then assessed those data after correcting for size increases in the current population compared with the Hamann-Todd Collection. Finally, we analyzed the data after both that size correction and adjustment for radiographic magnification. RESULTS: The average anterior-posterior canal diameter (and standard deviation) in all specimens at all levels was 14.1 +/- 1.6 mm. The canal diameters ranged from 9.0 to 20.9 mm, with a median diameter of 14.4 mm. Men had significantly larger cervical spinal canals than women at all of the levels that were evaluated. Specimens from donors who were sixty years of age or more at the time of death had significantly narrower canals than specimens from younger donors. There were no significant differences, with the numbers available, between black and white groups. After correcting for increased body size and adjusting for radiographic magnification, we estimated that cervical stenosis was present in 4.9% of the adult population, 6.8% of the population fifty years of age or older, and 9% of the population seventy years of age or older. CONCLUSIONS: Cervical spine stenosis appears to be very common. The radiographic finding of cervical stenosis should therefore be correlated with the clinical presentation prior to decision making regarding treatment. PMID- 17272454 TI - Improving tibial component coronal alignment during total knee arthroplasty with use of a tibial planing device. AB - BACKGROUND: The outcomes of knee arthroplasty have been shown to be affected by component alignment. Intramedullary and extramedullary alignment instrumentation are fairly effective for achieving the desired mean tibial component coronal alignment. However, there are outliers representing >3 degrees of varus or valgus alignment with respect to the anatomic tibial shaft axis. We measured the efficacy of a custom tibial planing device for reducing the outliers in tibial alignment. METHODS: We designed a tibial planing tool in an effort to improve tibial alignment. In one cohort (100 knees), we used traditional intramedullary alignment instrumentation to make the tibial bone cut. In a second cohort (120 knees), we used intramedullary alignment instrumentation to make the cut and also used a custom tool to check the cut and to correct an inexact cut. Tibial tray alignment relative to the long axis of the tibial shaft was measured in the coronal and sagittal planes on postoperative radiographs. The target coronal alignment was 90 degrees with respect to the tibial shaft axis (with <90 degrees denoting varus alignment). A total of 100 anteroposterior radiographs and sixty five lateral radiographs were analyzed for the group that was treated with traditional instrumentation alone, and a total of 120 anteroposterior radiographs and fifty-five lateral radiographs were analyzed for the group that was treated with use of the custom tibial planing device. RESULTS: The mean coronal alignment of the tibial component was 89.5 degrees +/- 2.1 degrees in the group that was treated with traditional instrumentation alone and 89.6 degrees +/- 1.4 degrees in the group that was treated with use of the custom planing device. Although the mean coronal alignment was not significantly different, the number of outliers was substantially reduced when the custom planing device was used. All 120 components that had been aligned with use of the custom planing device were within 3 degrees of the target coronal alignment, compared with only eighty-seven of the 100 components that had been implanted with use of traditional intramedullary alignment alone (p = 0.05). CONCLUSIONS: The use of a simple, inexpensive tibial planing device reduced the number of outliers due to tibial tray malalignment. Tibial varus has been associated with a higher risk of failure. Improving the accuracy of tibial component alignment may reduce the potential for poor clinical outcomes. PMID- 17272455 TI - Use of recombinant factor VIIa for hip surgery in a patient with factor-VII deficiency. A case report. PMID- 17272456 TI - Anterior interosseous nerve syndrome following shoulder arthroscopy. A report of three cases. PMID- 17272457 TI - Labor-related sacral and pubic fractures. A case report. PMID- 17272458 TI - Long-term follow-up of tuberculosis of the proximal part of the tibia involving the growth plate. A case report. PMID- 17272459 TI - Spontaneous, recurrent dislodgment of the polyethylene tibial insert after total knee arthroplasty. A case report. PMID- 17272460 TI - Gluteus maximus avulsion and closed degloving lesion associated with a thoracolumbar burst fracture. A case report. PMID- 17272461 TI - Atlantoaxial dislocation in a child secondary to a displaced chondrum terminale. A case report. PMID- 17272463 TI - Demystifying the orthopaedic certification process. PMID- 17272462 TI - Institutional review board approval: why it matters. AB - The modern institutional review boards originated in the 1970s. They exist to protect human subjects participating in research from potential harm. The Belmont Report provided the ethical principles (respect for persons, beneficence, and justice) that should be observed while conducting research on human subjects. Compliance with the ethical principles of the Belmont Report is a first step in successful submissions to an institutional review board. Regulations regarding conflict of interest represent an attempt to ensure that research is not biased by financial or other interest and to maintain public trust. PMID- 17272464 TI - An MBA: the utility and effect on physicians' careers. AB - BACKGROUND: Higher economic, legislative, legal, and administrative constraints in health-care services in the United States have led to an increase in physician dissatisfaction and a decrease in physician morale. In this study, we attempted to understand the motivation for a physician to enroll in a business school, and to discover the utility of the Master of Business Administration degree and how it changed the career path for the practicing clinician. METHOD: We conducted a retrospective study in which a twenty-seven-question survey was distributed by the United States Postal Service and by e-mail to 161 physician graduates of three East Coast business schools. The results were evaluated, and a statistical analysis was performed. RESULTS: Eighty-seven physicians (54%) responded. Eight surveys were discarded because of incomplete data or stray marks, leaving seventy nine surveys. The average age of the respondents was 41.4 years. The major motivations for going back to school included learning the business aspects of the health-care system (fifty-three respondents; 67%) and obtaining a more interesting job (forty-one respondents; 52%). The time that the respondents allocated for health-care-related activities before and after obtaining the degree was 58.3% and 31.8%, respectively, for patient care (p < 0.001); 8.5% and 3.68% for teaching (p < 0.001); 4.57% and 1.46% for basic-science research (p = 0.11); 4.23% and 4.55% for clinical research (p = 0.90); and 11.8% and 33.5% for administrative responsibilities (p < 0.001). The physicians stated that the most pertinent skills they had acquired were those related to evaluating systems operations and implementing improvements (thirty-nine respondents; 49%), learning how to be an effective leader (thirty-five; 44%), comprehending financial principles (thirty-three; 42%), working within a team (twenty-seven; 34%), and negotiating effectively (twenty-five; 32%). Sixty-four physicians (81%) believed that their business degree had been very useful or essential in the advancement of their careers. CONCLUSIONS: Many physicians decide to acquire a Master of Business Administration degree to understand the business of medicine. After they complete the degree program, their practice patterns substantially change, which is reflected particularly by an increase in time spent on administrative responsibilities. In order for physicians to overcome the multifaceted challenges of the evolving health-care system, it is essential to continue educating a proportion of physicians in both medicine and business. PMID- 17272465 TI - Influence of acetabular coverage on hip survival after free vascularized fibular grafting for femoral head osteonecrosis. PMID- 17272467 TI - Professionalism in publishing. PMID- 17272469 TI - Knowing what our primary care providers need to know. PMID- 17272470 TI - Custom patellofemoral replacement in the presence of trochlear dysplasia. PMID- 17272473 TI - Is arthroscopic release indicated? PMID- 17272475 TI - Patellar complications following distal femoral replacement after bone tumor resection. PMID- 17272477 TI - Operative and nonoperative treatments of medial collateral ligament rupture were not different in combined medial collateral and anterior cruciate ligament rupture. PMID- 17272479 TI - An elastic stockinette under a pneumatic tourniquet protected against the development of blisters during total knee arthroplasty. PMID- 17272478 TI - Customized or prefabricated foot orthoses improved function only in the short term in patients with plantar fasciitis. PMID- 17272480 TI - What's new in hand surgery. PMID- 17272483 TI - Standardization of insulin immunoassays: report of the American Diabetes Association Workgroup. AB - BACKGROUND: Circulating insulin concentration in serum or plasma provides important information for the estimation of insulin secretion and insulin resistance. Currently, lack of standardization of insulin assays hinders efforts to achieve consistent measures for treatment guidelines. METHODS: A Workgroup convened by the American Diabetes Association evaluated 12 different commercial insulin methods from 9 manufacturers. RESULTS: The within-assay CVs ranged from 3.7% to 39.0%, with 7 of 10 assays having a CV < or =10.6%. The among-assay CVs ranged from 12% to 66%, with a median value of 24%. A common insulin reference preparation did not change the among-assay CV and failed to improve harmonization of results among assays. Results from 6 of 10 assays agreed within the total error of 32% that is allowable based on biological variability criteria. Seven of 10 assays recovered insulin added to a serum pool within 15.5% of the expected concentration. In 9 of 10 methods, there was <2% cross-reactivity with intact human proinsulin, and 8 of 10 methods had <3% cross-reactivity with split (32, 33) proinsulin. For 9 of 10 assays, the cross-reactivity of des (64, 65) proinsulin exceeded 40%. Overall, most assays had acceptable imprecision and specificity for insulin. CONCLUSION: The discordance in test results for commercial insulin reagent sets is likely multifactorial and will require a continuing effort to understand the differences and achieve the desired consistency and harmonization among commercial immunoassays. PMID- 17272484 TI - Higher concentrations of alanine aminotransferase within the reference interval predict nonalcoholic fatty liver disease. AB - BACKGROUND: In nonalcoholic fatty liver disease (NAFLD), increased alanine aminotransferase (ALT) concentrations are considered to be a consequence of hepatocyte damage. We performed a prospective study to examine the association between ALT within its reference interval and risk for subsequent development of NAFLD. METHODS: The study cohort comprised 5237 healthy men without diagnosed NAFLD and without increases of either ALT (> or =35 U/L) or gamma glutamyltransferase (GGT; > or =40 U/L) above the reference intervals. We assessed alcohol intake via self-reporting (questionnaire) and performed biochemical tests for liver and metabolic function and abdominal ultrasonography. We used the Cox proportional hazards model to calculate the adjusted hazard ratios (aHRs) in the model for NAFLD. RESULTS: During 13 276.6 person-years of follow-up over a 4-year period, 984 new incident cases of NAFLD developed. We adjusted for age, weight change, body mass index, glucose, blood pressure, triglycerides, HDL cholesterol, smoking, alcohol consumption, regular exercise, homeostasis model assessment of insulin resistance, C-reactive protein, and incident diabetes. Compared with an ALT concentration of <16 U/L, aHR values (95% confidence intervals) for ALT concentrations were 1.53 (1.18-1.98), 1.66 (1.29 2.13), 1.62 (1.26-2.08), and 2.21 (1.73-2.81) for ALT concentrations of 16-18, 19 21, 22-25, and 26-34 U/L, respectively. This relationship remained significant even among normal-weight participants who were still within the reference interval of ALT and GGT at all follow-up examinations. CONCLUSIONS: In apparently healthy, nondiabetic Korean men, increased ALT concentration, even within the reference interval, was an independent predictor of incident NAFLD. PMID- 17272485 TI - Long-term stability of amino acids and acylcarnitines in dried blood spots. AB - BACKGROUND: Dried blood filter cards, collected for newborn screening, are often stored for long periods of time. They may be suitable for the retrospective diagnosis of inborn errors of metabolism, but no data are currently available on the long-term stability of amino acids and acylcarnitine species. METHODS: We analyzed amino acids and acylcarnitines by tandem mass spectrometry in 660 anonymous, randomly selected filter cards from 1989 through 2004. We assessed long-term stability of metabolites by linear regression and estimated annual decrease of concentration for each metabolite. RESULTS: Concentrations of free carnitine increased by 7.6% per year during the first 5 years of storage and decreased by 1.4% per year thereafter. Alanine, arginine, leucine, methionine, and phenylalanine decreased by 6.5%, 3.3%, 3.1%, 7.3%, and 5.7% per year, respectively. Acetylcarnitine, propionylcarnitine, citrulline, glycine, and ornithine decreased by 18.5%, 27.4%, 8.1%, 14.7%, and 16.3% per year during the first 5 years, respectively; thereafter the decline was more gradual. Tyrosine decreased by 1.7% per year during the first 5 years and 7.9% per year thereafter. We could not analyze medium- and long-chain acylcarnitine species because of low physiological concentrations. CONCLUSIONS: Estimation of the annual decrease of metabolites may allow for the retrospective diagnosis of inborn errors of metabolism in filter cards that have been stored for long periods of time. PMID- 17272486 TI - HPLC-electrospray tandem mass spectrometry for rapid determination of dihydropyrimidine dehydrogenase activity. AB - BACKGROUND: Patients with a partial dihydropyrimidine dehydrogenase (DPD) deficiency have an increased risk of developing severe 5-fluorouracil-associated toxicity. We developed a rapid and specific method to measure the DPD activity in peripheral blood mononuclear cells using HPLC tandem-mass spectrometry (HPLC MS/MS). METHODS: The activity of DPD was measured with thymine as the substrate, followed by reversed-phase HPLC combined with electrospray ionization MS/MS and detection of the product dihydrothymine with multiple-reaction monitoring. Stable isotope labeled dihydrothymine was used as the internal standard. RESULTS: Dihydrothymine was measured within an analytical run of 10 min, with a lower limit of quantification of 54 microg/L (0.4 micromol/L). The intraassay and interassay variations of the DPD activity assay were both <7%. A linear correlation (R(2) = 0.980; P <0.001) was observed between the HPLC-MS/MS data and those obtained with a reference method using radiolabeled thymine. There were no systematic differences between the 2 methods, and both methods yielded similar results. CONCLUSION: The analysis of the DPD activity with HPLC-MS/MS is rapid, accurate, and sufficiently sensitive to be used as a screening method for patients with a DPD deficiency. PMID- 17272487 TI - Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. AB - BACKGROUND: Discovery of the central role of hepcidin in body iron regulation has shed new light on the pathophysiology of iron disorders. Information is lacking on newer analytical approaches to measure hepcidin in serum and urine. Recent reports on the measurement of urine and serum hepcidin by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) necessitate analytical and clinical evaluation of MS-based methodologies. METHODS: We used SELDI-TOF MS, immunocapture, and tandem MS to identify and characterize hepcidin in serum and urine. In addition to diagnostic application, we investigated analytical reproducibility and biological and preanalytical variation for both serum and urine on Normal Phase 20 and Immobilized Metal Affinity Capture 30 ProteinChip arrays. We obtained samples from healthy controls and patients with documented iron-deficiency anemia, inflammation-induced anemia, thalassemia major, and hereditary hemochromatosis. RESULTS: Proteomic techniques showed that hepcidin-20, -22, and -25 isoforms are present in urine. Hepcidin-25 in serum had the same amino acid sequence as hepcidin-25 in urine, whereas hepcidin-22 was not detected in serum. The interarray CV was 15% to 27%, and interspot CV was 11% to 13%. Preliminary studies showed that hepcidin-25 differentiated disorders of iron metabolism. Urine hepcidin is more affected by multiple freeze-thaw cycles and storage conditions, but less influenced by diurnal variation, than is serum hepcidin. CONCLUSION: SELDI-TOF MS can be used to measure hepcidin in both serum and urine, but serum requires a standardized sampling protocol. PMID- 17272488 TI - Comparison of serum folate species analyzed by LC-MS/MS with total folate measured by microbiologic assay and Bio-Rad radioassay. AB - BACKGROUND: The Bio-Rad QuantaPhase II radioassay (BR), used for 25 years to measure total folate (TFOL) concentrations for the National Health and Nutrition Examination Survey (NHANES), will be discontinued in 2007. Liquid chromatography tandem mass spectrometry (LC-MS/MS) or a microbiologic assay (MA) will be used in the future. METHODS: We measured folate species by LC-MS/MS and TFOL by MA and BR in 327 serum samples. RESULTS: LC-MS/MS measured 5-methyltetrahydrofolic acid (5CH(3)THF; 82%), folic acid (FA; 8%), 5-formyltetrahydrofolic acid (5CHOTHF; 6%), tetrahydrofolic acid (THF; 4%), and 5,10-methenyltetrahydrofolic acid (5,10CH=THF; 0%). The sum of the folate species correlated well with TFOL measured by MA (R(2) = 0.97) and BR (R(2) = 0.91). Compared with LC-MS/MS results, MA and BR values were significantly lower (-6% and -29%, respectively); however, these differences were concentration dependent. The MA almost completely recovered folates added to serum samples except for FA [69% (3%)] and THF [36% (10%)]. The BR underrecovered 5CH(3)THF [61% (9%)] and 5CHOTHF [38% (14%)] and overrecovered 5,10CH=THF [234% (32%)]. Multiple linear regression models with log transformed data yielded a good fit for converting BR data to MA or LC-MS/MS data and MA data to LC-MS/MS data. CONCLUSIONS: The good correspondence between the sum of folate species determined by LC-MS/MS and TFOL determined by MA makes these 2 assays interchangeable. The BR produces much lower results, on average, probably because of 5CH(3)THF underrecovery. The conversion equations provided could be used for future NHANES time trend analyses. PMID- 17272489 TI - Standardized peptidome profiling of human urine by magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. AB - BACKGROUND: Peptidome profiling of human urine is a promising tool to identify novel disease-associated biomarkers; however, a wide range of preanalytical variables influence the results of peptidome analysis. Our aim was to develop a standardized protocol for reproducible urine peptidome profiling by means of magnetic bead (MB) separation followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). METHODS: MBs with defined surface functionalities (hydrophobic interaction, cation exchange, and metal ion affinity) were used for peptide fractionation of urine. Mass accuracy and imprecision were calculated for 9 characteristic mass signals (M(r), 1000-10,000). Exogenous variables (instrument performance, urine sampling/storage conditions, freezing conditions, and freeze-thaw cycles) and endogenous variables (pH, urine salt and protein concentrations, and blood and bacteria interferences) were investigated with urine samples from 10 male and 10 female volunteers. RESULTS: We detected 427 different mass signals in the urine of healthy donors. Within- and between-day imprecision in relative signal intensities ranged from 1% to 14% and from 4% to 16%, respectively. Weak cation exchange and metal ion affinity MB preparations required adjustment of the urinary pH to 7. Storage time, storage temperature, the number of freeze-thaw cycles, and bacterial and blood contamination significantly influenced urine peptide patterns. Individual urine peptide patterns differed significantly within and between days. This imprecision was diminished by normalization to a urinary protein content of 3.5 microg. CONCLUSION: This reliable pretreatment protocol allows standardization of preanalytical modalities and facilitates reproducible peptidome profiling of human urine by means of MB separation in combination with MALDI-TOF MS. PMID- 17272490 TI - Identification of a new metabolite of astilbin, 3'-O-methylastilbin, and its immunosuppressive activity against contact dermatitis. AB - BACKGROUND: Astilbin is a flavonoid isolated from the rhizome of Smilax glabra. In a previous study, we revealed its unique immunosuppressive activity, a selective inhibition against activated T lymphocytes. This characteristic of astilbin is beneficial for the treatment of human immune diseases. METHODS: We incubated astilbin with rat liver microsomal/cytosolic fractions and isolated the metabolite of astilbin, which was fully characterized by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. We administered astilbin orally via a gastric tube to rats at 0.22 mmol/kg and collected whole blood samples after 30 min and urine samples after 0 to 12 h. We applied HPLC and liquid chromatography/MS to measure the metabolite in the samples, and we assayed cytokine expression by reverse-transcription PCR. RESULTS: After incubation of astilbin with rat liver microsomal/cytosolic fractions, we detected a new metabolite of astilbin and isolated it from the culture solution. We characterized this metabolite by MS and NMR techniques as 3'-O-methylated astilbin. We detected the metabolite in both blood and urine samples after oral administration of astilbin, and the metabolite inhibited picryl chloride-induced ear swelling in mice and suppressed the expression of tumor necrosis factor-alpha and interferon-gamma, similarly to astilbin. CONCLUSION: This is the first identification of 3'-O-methylastilbin as a new flavonoid, as well as an active metabolite of astilbin in vivo, and is helpful for studying the kinetics of astilbin and its clinical applications. PMID- 17272491 TI - Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes. AB - BACKGROUND: Vitamin E isomers may protect against atherosclerosis. The aim of this study was to compare the effects of supplementation with either alpha tocopherol (alphaT) or mixed tocopherols rich in gamma-tocopherol (gammaT) on markers of oxidative stress and inflammation in patients with type 2 diabetes. METHODS: In a double-blind, placebo-controlled trial, 55 patients with type 2 diabetes were randomly assigned to receive (500 mg/day) (a) alphaT, (b) mixed tocopherols, or (c) placebo for 6 weeks. Cellular tocopherols, plasma and urine F(2)-isoprostanes, erythrocyte antioxidant enzyme activities, plasma inflammatory markers, and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation. RESULTS: Neutrophil alphaT and gammaT increased (both P <0.001) with mixed tocopherol supplementation, whereas alphaT (P <0.001) increased and gammaT decreased (P <0.005) after alphaT supplementation. Both alphaT and mixed tocopherol supplementation resulted in reduced plasma F(2) isoprostanes (P <0.001 and P = 0.001, respectively) but did not affect 24-h urinary F(2)-isoprostanes or erythrocyte antioxidant enzyme activities. Neither alphaT nor mixed tocopherol supplementation affected plasma C-reactive protein, interleukin 6, tumor necrosis factor-alpha, or monocyte chemoattractant protein 1. Stimulated neutrophil leukotriene B(4) production decreased significantly in the mixed tocopherol group (P = 0.02) but not in the alphaT group (P = 0.15). CONCLUSIONS: The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes. In populations with well-controlled type 2 diabetes, supplementation with either alphaT or mixed tocopherols rich in gammaT is unlikely to confer further benefits in reducing inflammation. PMID- 17272492 TI - Malarial fever: hemozoin is involved but Toll-free. PMID- 17272494 TI - Commentary: stem cell research continues in Korea beyond the Hwang scandal. PMID- 17272493 TI - The incredible, edible, and therapeutic egg. PMID- 17272495 TI - Meeting report: the first international collaborative symposium on stem cell research, Seoul, Korea. PMID- 17272496 TI - Sonic hedgehog and other soluble factors from differentiating embryoid bodies inhibit pancreas development. AB - Success of cell-replacement therapy for diabetes will largely depend on the establishment of alternative sources of pancreatic islet grafts. Embryonic stem (ES) cell differentiation toward pancreatic insulin-producing cells offers such perspectives, but there are still many challenges to overcome. Our previous studies suggested that the limited amount of insulin-positive cells derived from ES cells is related to the activation of pancreas inhibitory signals. To confirm this hypothesis, we report here that exposure of mouse embryonic pancreas explants to soluble factors from embryoid bodies (EBs) inhibits growth, morphogenesis, and endocrine and exocrine differentiation as evaluated by explant size and mRNA and protein expression. Sonic Hedgehog (Shh), an established pancreas repressor both at early and late developmental stages, was produced and secreted by EBs, and participated in the inhibitory effect by inducing its target Gli1 in the explants. Inhibition of Hedgehog pathway rescued the differentiation of Insulin-positive cells in the explants. In contrast to pancreatic cells, hepatic progenitors exposed to EB-conditioned medium showed improved differentiation of albumin-positive cells. In a model system of ES cell differentiation in vitro, we found that definitive endoderm induction by serum removal or activin A treatment further increased Hedgehog production and activity in EBs. Concomitantly, downregulation of the pancreas marker Pdx1 was recorded in activin-treated EBs, a phenomenon that was prevented by antagonizing Hedgehog signaling with Hedgehog interacting protein. These data strongly suggest that Hedgehog production in EBs limits pancreatic fate acquisition and forms a major obstacle in the specification of pancreatic cells from ES-derived definitive endoderm. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17272498 TI - Host vascular niche contributes to myocardial repair induced by intracoronary transplantation of bone marrow CD34+ progenitor cells in infarcted swine heart. AB - The effects of bone marrow cell transplantation (BMT) on myocardial infarct might be affected by host intrinsic circumferences. A best vascular niche was shown in the infarcted hearts with collateral vessels at 2 weeks after myocardial infarction (MI). BMT caused the greatest cardiac repairs after MI in the swine with better collateral vessels, which might be relative to richer collateral vessels, greater vessel densities, and higher expressions of basif fibroblast growth factor and stromal cell-derived factor-1 in the hearts before BMT. Our data suggest that existence of intrinsic collateral vessels contributes greatly to the beneficial effects of intracoronary BMT on cardiac repairs after MI. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17272497 TI - Whole genome analysis of human neural stem cells derived from embryonic stem cells and stem and progenitor cells isolated from fetal tissue. AB - Multipotent neural stem cells (NSC) have been derived from human embryonic stem cells (hESC) as well as isolated from fetal tissues. However, there have been few exclusive markers of NSC identified to date, and the differences between NSC from various sources are poorly understood. Although cells isolated from these two sources share many important characteristics, it is not clear how closely they are related in terms of gene expression. Here, we compare the gene expression profiles of 11 lines of NSC derived from hESC (ES_NSC), four lines of NSC isolated from fetus (F_NSC), and two lines of restricted progenitors in order to characterize these cell populations and identify differences between NSC derived from these two sources. We showed that ES_NSC were clustered together with high transcriptional similarities but were distinguished from F_NSC, oligodendrocyte precursor cells, and astrocyte precursor cells. There were 17 genes expressed in both ES_NSC and F_NSC whose expression was not identified in restricted neural progenitors. Furthermore, the major differences between ES_NSC and F_NSC were mostly observed in genes related to the key neural differentiation pathways. Here, we show that comparison of global gene expression profiles of ES_NSC, F_NSC, and restricted neural progenitor cells makes it possible to identify some of the common characteristics of NSC and differences between similar stem cell populations derived from hESCs or isolated from fetal tissue. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17272499 TI - Genome-wide reprogramming in hybrids of somatic cells and embryonic stem cells. AB - Recent experiments demonstrate that somatic nuclei can be reprogrammed to a pluripotent state when fused to ESCs. The resulting hybrids are pluripotent as judged by developmental assays, but detailed analyses of the underlying molecular genetic control of reprogrammed transcription in such hybrids are required to better understand fusion-mediated reprogramming. We produced hybrids of mouse ESCs and fibroblasts that, although nearly tetraploid, exhibit characteristics of normal ESCs, including apparent immortality in culture, ESC-like colony morphology, and pluripotency. Comprehensive analysis of the mouse embryonic fibroblast/ESC hybrid transcriptome revealed global patterns of gene expression reminiscent of ESCs. However, combined analysis of variance and hierarchical clustering analyses revealed at least seven distinct classes of differentially regulated genes in comparisons of hybrids, ESCs, and somatic cells. The largest class includes somatic genes that are silenced in hybrids and ESCs, but a smaller class includes genes that are expressed at nearly equivalent levels in hybrids and ESCs that contain many genes implicated in pluripotency and chromatin function. Reprogrammed genes are distributed throughout the genome. Reprogramming events include both transcriptional silencing and activation of genes residing on chromosomes of somatic origin. Somatic/ESC hybrid cell lines resemble their pre fusion ESC partners in terms of behavior in culture and pluripotency. However, they contain unique expression profiles that are similar but not identical to normal ESCs. ESC fusion-mediated reprogramming provides a tractable system for the investigation of mechanisms of reprogramming. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17272500 TI - Q2ChIP, a quick and quantitative chromatin immunoprecipitation assay, unravels epigenetic dynamics of developmentally regulated genes in human carcinoma cells. AB - Chromatin immunoprecipitation (ChIP) is a key technique for studying protein-DNA interactions and mapping epigenetic histone modifications on DNA. Current ChIP protocols require extensive sample handling and large cell numbers. We developed a quick and quantitative (Q(2))ChIP assay suitable for histone and transcription factor immunoprecipitation from chromatin amounts equivalent to as few as 100 cells. DNA-protein cross-linking in suspension in presence of butyrate, elimination of background chromatin through a tube shift after washes, and a combination of cross-link reversal, protein digestion, increased antibody-bead to chromatin ratio, and DNA elution into a single step considerably improve ChIP efficiency and shorten the procedure. We used Q(2)ChIP to monitor changes in histone H3 modifications on the 5' regulatory regions of the developmentally regulated genes OCT4, NANOG, LMNA, and PAX6 in the context of retinoic-acid mediated human embryonal carcinoma cell differentiation. Quantitative polymerase chain reaction analysis of precipitated DNA unravels biphasic heterochromatin assembly on OCT4 and NANOG, involving H3 lysine (K)9 and K27 methylation followed by H3K9 deacetylation and additional H3K27 trimethylation. Di- and trimethylation of H3K4 remain relatively unaltered. In contrast, PAX6 displays histone modifications characteristic of repressed genes with potential for activation in undifferentiated cells. PAX6 undergoes H3K9 acetylation and enhanced H3K4 trimethylation upon transcriptional activation. Q(2)ChIP of the transcription factor Oct4 demonstrates its dissociation from the NANOG promoter upon differentiation. This study is, to our knowledge, the first to reveal histone modification changes on human OCT4 and NANOG regulatory sequences. The results demonstrate ordered chromatin rearrangement on developmentally regulated promoters upon differentiation. PMID- 17272501 TI - The thymic theme of acetylcholinesterase splice variants in myasthenia gravis. AB - Cholinergic signaling and acetylcholinesterase (AChE) influence immune response and inflammation. Autoimmune myasthenia gravis (MG) is mediated by antibodies to the acetylcholine receptor and current therapy is based on anti-AChE drugs. MG is associated with thymic hyperplasia, showing signs of inflammation. The objectives of this study were to analyze the involvement of AChE variants in thymic hyperplasia. We found lower hydrolytic activities in the MG thymus compared with adult controls, accompanied by translocation of AChE-R from the cytoplasm to the membrane and increased expression of the signaling protein kinase PKC-betaII. To explore possible causal association of AChE-R changes with thymic composition and function, we used an AChE-R transgenic model and showed smaller thymic medulla compared with strain-matched controls, indicating that AChE-R overexpression interferes with thymic differentiation mechanisms. Interestingly, AChE-R transgenic mice showed increased numbers of CD4(+)CD8(+) cells that were considerably more resistant in vitro to apoptosis than normal thymocytes, suggesting possibly altered positive selection. We further analyzed microarray data of MG thymic hyperplasia compared with healthy controls and found continuous and discrete changes in AChE-annotated GO categories. Together, these findings show that modified AChE gene expression and properties are causally involved in thymic function and development. PMID- 17272502 TI - Kringle 5 of human plasminogen, an angiogenesis inhibitor, induces both autophagy and apoptotic death in endothelial cells. AB - Inhibition of endothelial cell proliferation and angiogenesis is emerging as an important strategy in cancer therapeutics. Kringle 5 (K5) of human plasminogen is a potent angiogenesis inhibitor. Previous studies have shown K5 exposure promotes caspase activity and apoptosis in endothelial cells. Here we report that K5 treatment evokes an autophagic response in endothelial cells that is specific and initiated even in the absence of nutritional stress. Endothelial cells exposed to K5 up-regulated Beclin 1 levels within a few hours. Furthermore, progressively increasing amounts of antiapoptotic Bcl-2 were found to be complexed with Beclin 1, although total levels of Bcl-2 remained unchanged. Prolonged exposure to K5 ultimately led to apoptosis via mitochondrial membrane depolarization and caspase activation in endothelial cells. Knocking down Beclin 1 levels by RNA interference decreased K5 induced autophagy but accelerated K5-induced apoptosis. These studies suggest that interfering with the autophagic survival response can potentiate the antiangiogenic effects of Kringle 5 in endothelial cells. PMID- 17272505 TI - Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura. AB - Chronic autoimmune thrombocytopenic purpura (AITP) is associated with autoantibodies specific for platelet membrane components, often including glycoprotein GPIIIa. T helper (Th) cells reactive with GPIIIa, which are capable of driving the autoantibody response, are activated in AITP, and the aim here was to map the epitopes that they recognize. Peripheral blood mononuclear cells (PBMCs) were obtained from 31 patients with AITP and 30 control donors and stimulated with a panel of 86 overlapping synthetic 15-mer peptides spanning the complete sequence of GPIIIa. One or more peptides elicited recall proliferation by PBMCs from 28 of the patients, and, typically, multiple sequences were stimulatory. In contrast, responses in healthy control donors were rare (chi square test = 115.967; P 10 years) T cell production. PMID- 17272508 TI - Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils. AB - CD33-related Siglecs (CD33rSiglecs) are a family of sialic acid-recognizing lectins on immune cells whose biologic functions are unknown. We studied in vivo functions of Siglec-F, the CD33rSiglec expressed on mouse eosinophils, which are prominent in allergic processes. Induction of allergic lung inflammation in mice caused up-regulation of Siglec-F on blood and bone marrow eosinophils, accompanied by newly induced expression on some CD4(+) cells, as well as quantitative up-regulation of endogenous Siglec-F ligands in the lung tissue and airways. Taken together with the tyrosine-based inhibitory motif in the cytosolic tail of Siglec-F, the data suggested a negative feedback loop, controlling allergic responses of eosinophils and helper T cells, via Siglec-F and Siglec-F ligands. To pursue this hypothesis, we created Siglec-F-null mice. Allergen challenged null mice showed increased lung eosinophil infiltration, enhanced bone marrow and blood eosinophilia, delayed resolution of lung eosinophilia, and reduced peribronchial-cell apoptosis. Anti-Siglec-F antibody cross-linking also enhanced eosinophil apoptosis in vitro. These data support the proposed negative feedback role for Siglec-F, represent the first in vivo demonstration of biologic functions for any CD33rSiglec, and predict a role for human Siglec-8 (the isofunctional paralog of mouse Siglec-F) in regulating the pathogenesis of human eosinophil-mediated disorders. PMID- 17272511 TI - Neutrophil elastase depends on serglycin proteoglycan for localization in granules. AB - Granule proteins play a major role in bacterial killing by neutrophils. Serglycin proteoglycan, the major intracellular proteoglycan of hematopoietic cells, has been proposed to play a role in sorting and packing of granule proteins. We examined the content of major neutrophil granule proteins in serglycin knockout mice and found neutrophil elastase absent from mature neutrophils as shown by activity assay, Western blotting, and immunocytochemistry, whereas neutrophil elastase mRNA was present. The localization of other neutrophil granule proteins did not differ between wild-type and serglycin knockout mice. Differential counts and neutrophil ultrastructure were unaffected by the lack of serglycin, indicating that defective localization of neutrophil elastase does not induce neutropenia itself, albeit mutations in the neutrophil elastase gene can cause severe congenital neutropenia or cyclic neutropenia. The virulence of intraperitoneally injected Gram-negative bacteria (Klebsiella pneumoniae) was increased in serglycin knockout mice compared with wild-type mice, as previously reported for neutrophil elastase knockout mice. Thus, serglycin proteoglycan has an important role in localizing neutrophil elastase in azurophil granules of neutrophils, while localization of other granule proteins must be mediated by other mechanisms. PMID- 17272512 TI - Chronic psychological stress alters epithelial cell turn-over in rat ileum. AB - Dysregulated epithelial cell kinetics associated with mucosal barrier dysfunction may be involved in certain intestinal disorders. We previously showed that chronic psychological stress, in the form of repetitive sessions of water avoidance stress (WAS), has a major detrimental impact on ileal barrier function. We hypothesized that these changes were related to a disturbance in enterocyte kinetics. Rats were submitted to WAS (1 h/day) for 5 or 10 days. As previously shown, permeability to macromolecules was enhanced in rats stressed for 5 and 10 days compared with controls. WAS induced a decrease in crypt depth at day 5 associated with an increased number of apoptotic cells. Cell proliferation was significantly increased at days 5 and 10. Villus height and the specific activity of sucrase were significantly reduced at day 10. We concluded that WAS induces a disturbance of epithelial cell kinetics, with the pattern depending on the duration of the stress period. These findings help to explain the mechanism underlying altered epithelial barrier function resulting from exposure to chronic psychological stress. PMID- 17272515 TI - Altered protein expression at early-stage rat hepatic neoplasia. AB - Protein expression patterns were analyzed in a rat model of hepatic neoplasia to detect changes reflecting biological mechanism or potential therapeutic targets. The rat resistant hepatocyte model of carcinogenesis was studied, with a focus on the earliest preneoplastic lesion visible in the liver, the preneoplastic hyperplastic nodule. Expression differences were shown by two-dimensional polyacrylamide gel electrophoresis and image analysis. Polypeptide masses were measured by peptide mass fingerprinting using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) and their sequences were obtained by tandem mass spectrometry. Alterations in expression of cytoskeletal and functional proteins were demonstrated, consistent with biological changes known to occur in the preneoplastic cells. Of particular interest was the differential expression of a serine protease inhibitor (serpin) with a role implicated in angiogenesis. Serpin, implicated in the inhibition of angiogenesis, is present in normal liver but has greatly reduced expression at the preneoplastic stage of liver cancer development. Immunofluorescence microscopy with antibodies to this serpin, kallistatin, supports the proteomic identification. Immunofluorescence microscopy with antibodies to the blood vessel marker von Willebrand factor provides evidence for neovascularization in the liver containing multiple preneoplastic nodules. These observations suggest that at an early stage of liver carcinogenesis reduction or loss of angiogenesis inhibitors may contribute to initiation of neoangiogenesis. A number of other identified proteins known to be associated with hepatomas are also present at early-stage neoplasia. PMID- 17272514 TI - cFLIPL prevents TRAIL-induced apoptosis of hepatocellular carcinoma cells by inhibiting the lysosomal pathway of apoptosis. AB - Sensitivity to TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis and the lysosomal pathway of cell death are features of cancer cells. However, it is unknown if TRAIL cytotoxic signaling engages the lysosomal pathway of cell death. Our aim, therefore, was to ascertain if TRAIL killing involves lysosomal permeabilization. TRAIL-induced apoptosis of hepatocellular carcinoma cells (HuH 7, Hep3B) was associated with lysosomal permeabilization, as demonstrated by redistribution of the lysosomal protease cathepsin B into the cytosol. Pharmacological and short hairpin RNA-targeted inhibition of cathepsin B reduced apoptosis. Because cellular FLICE-inhibitory protein (cFLIP) inhibits TRAIL induced cell death and is frequently overexpressed by human cancers, the ability of cFLIP to prevent lysosomal permeabilization during TRAIL treatment was examined. Enforced long-form cFLIP (cFLIP(L)) expression reduced release of cathepsin B from lysosomes and attenuated apoptosis. cFLIP(L) overexpression was also associated with robust p42/44 MAPK activation following exposure to TRAIL. In contrast, cFLIP(L) overexpression attenuated p38 MAPK activation and had no significant effect on JNK and NF-kappaB activation. Inhibition of p42/44 MAPK by PD98059 restored TRAIL-mediated lysosomal permeabilization and apoptosis in cFLIP overexpressing cells. In conclusion, these results demonstrate that lysosomal permeabilization contributes to TRAIL-induced apoptosis of hepatocellular carcinoma cells and suggest that cFLIP(L) cytoprotection is, in part, due to p42/44 MAPK-dependent inhibition of lysosomal breakdown. PMID- 17272513 TI - Nuclear receptors RXRalpha:RARalpha are repressors for human MRP3 expression. AB - Multidrug resistance-associated protein MRP3/Mrp3 (ABCC3) is upregulated in cholestasis, an adaptive response that may protect the liver from accumulation of toxic compounds, such as bile salts and bilirubin conjugates. However, the mechanism of this upregulation is poorly understood. We and others have previously reported that fetoprotein transcription factor/liver receptor homolog 1 is an activator of MRP3/Mrp3 expression. In searching for additional regulatory elements in the human MRP3 promoter, we have now identified nuclear receptor retinoic X receptor-alpha:retinoic acid receptor-alpha (RXRalpha:RARalpha) as a repressor of MRP3 activation by transcription factor Sp1. A luciferase reporter assay demonstrated that cotransfection of transcription factor Sp1 stimulates the MRP3 promoter activity and that additions of RXRalpha:RARalpha abrogated this activation in a dose-dependent manner. Site mutations and gel shift assays have identified a Sp1 binding GC box motif at -113 to -108 nts upstream from the MRP3 translation start site, where RXRalpha:RARalpha specifically reduced Sp1 binding to this site. Mutation of the GC box also reduced MRP3 promoter activity. The functional role of RXRalpha:RARalpha as a repressor of MRP3 expression was further confirmed by RARalpha small-interfering RNA knockdown in HepG2 cells, which upregulated endogenous MRP3 expression. In summary, our results indicate that activator Sp1 and repressor RXRalpha:RARalpha act in concert to regulate MRP3 expression. Since RXRalpha:RARalpha expression is diminished by cholestatic liver injury, loss of RXRalpha:RARalpha may lead to upregulation of MRP3/Mrp3 expression in these disorders. PMID- 17272516 TI - Gata4 and Hnf1alpha are partially required for the expression of specific intestinal genes during development. AB - The terminal differentiation phases of intestinal development in mice occur during cytodifferentiation and the weaning transition. Lactase-phlorizin hydrolase (LPH), liver fatty acid binding protein (Fabp1), and sucrase-isomaltase (SI) are well-characterized markers of these transitions. With the use of gene inactivation models in mature mouse jejunum, we have previously shown that a member of the zinc finger transcription factor family (Gata4) and hepatocyte nuclear factor-1alpha (Hnf1alpha) are each indispensable for LPH and Fabp1 gene expression but are both dispensable for SI gene expression. In the present study, we used these models to test the hypothesis that Gata4 and Hnf1alpha regulate LPH, Fabp1, and SI gene expression during development, specifically focusing on cytodifferentiation and the weaning transition. Inactivation of Gata4 had no effect on LPH gene expression during either cytodifferentiation or suckling, whereas inactivation of Hnf1alpha resulted in a 50% reduction in LPH gene expression during these same time intervals. Inactivation of Gata4 or Hnf1alpha had a partial effect ( approximately 50% reduction) on Fabp1 gene expression during cytodifferentiation and suckling but no effect on SI gene expression at any time during development. Throughout the suckling period, we found a surprising and dramatic reduction in Gata4 and Hnf1alpha protein in the nuclei of absorptive enterocytes of the jejunum despite high levels of their mRNAs. Finally, we show that neither Gata4 nor Hnf1alpha mediates the glucocorticoid induced precocious maturation of the intestine but rather are downstream targets of this process. Together, these data demonstrate that specific intestinal genes have differential requirements for Gata4 and Hnf1alpha that are dependent on the developmental time frame in which they are expressed. PMID- 17272517 TI - MIP-3alpha neutralizing monoclonal antibody protects against TNBS-induced colonic injury and inflammation in mice. AB - A characteristic feature of human inflammatory bowel disease, particularly Crohn's disease, is the presence of activated CD4(+) T cells. Recently, we have shown that colonic epithelial cell production of macrophage inflammatory protein (MIP)-3alpha, a CD4 T cell-directed chemokine, is elevated in inflammatory bowel disease. However, the functional relevance of MIP-3alpha production during intestinal inflammation is poorly understood. The aim of this study was to determine whether MIP-3alpha production is increased during murine 2,4,6 trinitrobenzene sulfonic acid (TNBS)-induced colitis and to examine the effect of anti-MIP-3alpha neutralizing monoclonal antibody administration in this model. We found that the administration of TNBS significantly increased colonic MIP-3alpha protein levels in Balb/c mice. Consistent with this, a marked increase in the number of CCR6-bearing lamina propria CD4(+) and CD8(+) T cells was also observed in TNBS-treated animals. Treatment of mice with an anti-MIP-3alpha neutralizing monoclonal antibody significantly reduced TNBS-mediated increases in colonic weight-to-length ratio, mucosal ulceration, histological damage, and myeloperoxidase activity. TNBS-mediated increases in the number of CCR6-bearing lamina propria T cells were also substantially reduced by anti-MIP-3alpha neutralizing monoclonal antibody treatment. Taken together, our findings indicate that blockade of MIP-3alpha bioactivity can significantly reduce TNBS-mediated colonic injury and T cell recruitment, suggesting a role for this chemokine in the pathophysiology of intestinal inflammation. PMID- 17272518 TI - Nitric oxide inhibits enterocyte migration through activation of RhoA-GTPase in a SHP-2-dependent manner. AB - Diseases of intestinal inflammation like necrotizing enterocolitis (NEC) are associated with impaired epithelial barrier integrity and the sustained release of intestinal nitric oxide (NO). NO modifies the cytoskeletal regulator RhoA GTPase, suggesting that NO could affect barrier healing by inhibiting intestinal restitution. We now hypothesize that NO inhibits enterocyte migration through RhoA-GTPase and sought to determine the pathways involved. The induction of NEC was associated with increased enterocyte NO release and impaired migration of bromodeoxyuridine-labeled enterocytes from terminal ileal crypts to villus tips. In IEC-6 enterocytes, NO significantly inhibited enterocyte migration and activated RhoA-GTPase while increasing the formation of stress fibers. In parallel, exposure of IEC-6 cells to NO increased the phosphorylation of focal adhesion kinase (pFAK) and caused a striking increase in cell-matrix adhesiveness, suggesting a mechanism by which NO could impair enterocyte migration. NEC was associated with increased expression of pFAK in the terminal ileal mucosa of wild-type mice and a corresponding increase in disease severity compared with inducible NO synthase knockout mice, confirming the dependence of NO for FAK phosphorylation in vivo and its role in the pathogenesis of NEC. Strikingly, inhibition of the protein tyrosine phosphatase SHP-2 in IEC-6 cells prevented the activation of RhoA by NO, restored focal adhesions, and reversed the inhibitory effects of NO on enterocyte migration. These data indicate that NO impairs mucosal healing by inhibiting enterocyte migration through activation of RhoA in a SHP-2-dependent manner and support a possible role for SHP-2 as a therapeutic target in diseases of intestinal inflammation like NEC. PMID- 17272519 TI - Vesicoureteral reflux. PMID- 17272520 TI - Pediatric migraine. PMID- 17272521 TI - Vision screening essentials: screening today for eye disorders in the pediatric patient. PMID- 17272522 TI - Index of suspicion. PMID- 17272524 TI - Focus on diagnosis: co-oximetry. PMID- 17272523 TI - Complementary, holistic, and integrative medicine: St. John's wort. PMID- 17272525 TI - Nonsteroidal anti-inflammatory drugs and abdominal pain. PMID- 17272526 TI - Otitis externa. PMID- 17272528 TI - Venlafaxine for major depression. PMID- 17272529 TI - Childhood intelligence and being a vegetarian. PMID- 17272530 TI - Leprosy after starting antiretroviral treatment. PMID- 17272531 TI - Emergency care in the first 48 hours. PMID- 17272532 TI - Allergy to hair dye. PMID- 17272533 TI - Schizophrenia can and should be renamed. PMID- 17272534 TI - Systematic review addresses socioeconomic inequalities. PMID- 17272535 TI - Education programme has changed since study. PMID- 17272538 TI - Giving a voice to the unheard. PMID- 17272536 TI - ISTC programme is an expensive option. PMID- 17272539 TI - Ghost authorship of industry funded drug trials is common, say researchers. PMID- 17272541 TI - 500m dollars investment in poor countries' health systems will boost vaccination. PMID- 17272542 TI - Bush proposes plan to expand health insurance coverage. PMID- 17272543 TI - Patients should get be able to have dialysis closer to home. PMID- 17272544 TI - More than 200,000 people ask Novartis to drop its challenge on drug patent. PMID- 17272546 TI - Publishers hire PR heavyweight to defend themselves against open access. PMID- 17272547 TI - Dutch court acquits suicide counsellor of breaking the law. PMID- 17272548 TI - Doctors disagree over detention of patients with extensively drug resistant tuberculosis. PMID- 17272553 TI - Ontario to screen for colorectal cancer . PMID- 17272554 TI - And the Oscar goes to . . . Salvarsan. PMID- 17272561 TI - First picturesOne for the album. PMID- 17272562 TI - Is doctors' self interest undermining the National Health Service. PMID- 17272563 TI - Is doctors' self interest undermining the National Health Service? PMID- 17272564 TI - So how much do doctors really earn? PMID- 17272565 TI - Is the president's plan dead even before arrival? PMID- 17272566 TI - Defining limits in care of terminally ill patients. PMID- 17272568 TI - Headaches. PMID- 17272567 TI - Endometriosis. PMID- 17272569 TI - Penetrating trauma to the junctional zone needs aggressive management. PMID- 17272570 TI - Newly diagnosed iron deficiency anaemia in a premenopausal woman. PMID- 17272577 TI - Does access to a medical home differ according to child and family characteristics, including special-health-care-needs status, among children in Alabama? AB - OBJECTIVE: Our goal was to examine relationships among access to a medical home, special-health-care-needs status, and child and family characteristics in one Southern state. We hypothesized that access to a medical home is influenced by several family and child sociodemographic characteristics, including special health-care status. METHODS: We used data from the 2003 National Survey of Children's Health. The study sample comprised all Alabama resident children. The main dependent variable was a medical home; the primary independent variable classified children according to children-with-special-health-care-needs status. We controlled for child age, gender, race, family structure, health status, insurance coverage, household education, and poverty. We first explored means or proportions for the study variables and then estimated multivariate logistic regression models. RESULTS: Children with special health care needs were significantly more likely than children without special health care needs to have a personal doctor or nurse, to have a preventive health care visit in the previous 12 months, and to have good communication with their provider. Children with special health care needs were also more likely to experience problems accessing specialty care, equipment, or services. Being uninsured, living at or near the federal poverty level, in a household where no one completed high school, being black, having less than excellent or good health, and living in a nontraditional family structure were characteristics associated with being less likely to have a medical home. In general, children-with-special-health-care needs status was not related to having a medical home, but dependency on prescription medicine was. CONCLUSIONS: Assuring that all children, irrespective of family income, have access to and are enrolled in health insurance plans will move us closer to the national goal of having a medical home for all children, especially those with a special health care need, by 2010. PMID- 17272578 TI - The relationship between autism and parenting stress. AB - OBJECTIVE: We assessed associations between parenting a child with autism and stress indicators. METHODS: In the 2003 National Survey of Children's Health, parents or other knowledgeable adult respondents for children aged 4 to 17 years reported their recent feelings about their life sacrifices to care for their child, difficulty caring for their child, frustration with their child's actions, and anger toward their child. Responses were compiled in the Aggravation in Parenting Scale. Parents of children reported to have autism (N = 459) were compared with parents of: (1) children with special health care needs including emotional, developmental, or behavioral problems other than autism that necessitated treatment (children with other developmental problems [N = 4545]); (2) children with special health care needs without developmental problems (N = 11475); and (3) children without special health care needs (N = 61826). Weighted estimates are presented. RESULTS: Parents of children with autism were more likely to score in the high aggravation range (55%) than parents of children with developmental problems other than autism (44%), parents of children with special health care needs without developmental problems (12%), and parents of children without special health care needs (11%). However, within the autism group, the proportion of parents with high aggravation was 66% for those whose child recently needed special services and 28% for those whose child did not. The parents of children with autism and recent special service needs were substantially more likely to have high aggravation than parents of children with recent special service needs in each of the 3 comparison groups. Conversely, parents of children with autism but without recent special service needs were not more likely to have high aggravation than parents of children with other developmental problems. CONCLUSIONS: Parenting a child with autism with recent special service needs seems to be associated with unique stresses. PMID- 17272580 TI - Final commentary on the special volume of articles from the National Survey of Children's Health. PMID- 17272579 TI - Disparities in dental insurance coverage and dental care among US children: the National Survey of Children's Health. AB - OBJECTIVES: We sought to understand disparities in dental insurance coverage and dental care among US children by race/ethnicity, urban/rural residence, and socioeconomic status. METHODS: Linked data from the National Survey of Children's Health and Area Resource File were analyzed (N = 89 071). Multiple logistic regression analysis was used to adjust for confounders. RESULTS: A total of 22.1% of US children lacked parentally reported dental insurance coverage in the preceding year, 26.9% did not have a routine preventive dental visit, and 5.1% had parentally perceived unmet need for preventive dental care. US-born minority children were less likely to lack dental insurance than US-born white children; however, foreign-born Hispanic children were more likely to be uninsured. Rural children were more likely to be uninsured than urban children. Children with health insurance were more likely to have dental coverage. Children who lacked dental insurance were less likely to have received preventive care and more likely to have unmet need for care. Compared with US-born white children, all minority children were less likely to receive preventive care. These disparities were exacerbated among foreign-born children. Fewer race-based disparities were found for unmet need for dental care. Only black children, both US- and foreign born, had higher odds of unmet need for preventive services than US-born white children. Poor dental health was strongly associated with unmet need. Disparities in dental insurance coverage and dental care are also evident by family socioeconomic status. CONCLUSIONS: Poor and minority children were less likely to receive preventive dental care, even when insurance status was considered. Rural children were less likely to have dental insurance than urban children. Foreign birth affected insurance status for Hispanic children and use of preventive services for all minority children. PMID- 17272581 TI - Children's mental health and family functioning in Rhode Island. AB - OBJECTIVES: Our objectives were to (a) estimate the prevalence of children's mental health problems, (b) assess family functioning, and (c) investigate the relationship between children's mental health and family functioning in Rhode Island. METHODS: From the 2003 National Survey of Children's Health, Rhode Island data for children 6 to 17 years of age were used for the analyses (N = 1326). Two aspects of family functioning measures, parental stress and parental involvement, were constructed and were examined by children's mental health problems, as well as other child and family characteristics (child's age, gender, race/ethnicity, special needs, parent's education, income, employment, family structure, number of children, and mother's general and mental health). Bivariate analyses and multivariate logistic regression were used to investigate the relationship. RESULTS: Among Rhode Island children, nearly 1 (19.0%) in 5 had mental health problems, 1 (15.6%) in 6 lived with a highly stressed parent, and one third (32.7%) had parents with low involvement. Bivariate analyses showed that high parental stress and low parental involvement were higher among parents of children with mental health problems than parents of children without those problems (33.2% vs 11.0% and 41.0% vs 30.3%, respectively). In multivariate logistic regression, parents of children with mental health problems had nearly 4 times the odds of high stress compared with parents of children without those problems. When children's mental health problems were severe, the odds of high parental stress were elevated. However, children's mental health was not associated with parental involvement. CONCLUSIONS: Children's mental health was strongly associated with parental stress, but it was not associated with parental involvement. The findings indicate that when examining the mental health issues of children, parental mental health and stress must be considered. PMID- 17272582 TI - Sleepless in America: inadequate sleep and relationships to health and well-being of our nation's children. AB - OBJECTIVE: Our goal was to identify characteristics associated with inadequate sleep for a national random sample of elementary school-aged children (6-11 years) and adolescents (12-17 years). METHODS: Data from 68418 participants in the 2003 National Survey of Children's Health were analyzed by using weighted bivariate and multivariate regression models. The dependent variable was report of not getting enough sleep for a child of his or her age >or=1 night of the past week. Independent variables included demographic characteristics, child health, school and other activities, and family life. RESULTS: Parents of elementary school-aged children with inadequate sleep were more likely to report that their child was having problems at school or had a father with fair or poor health. Parents of adolescents with inadequate sleep were more likely to report that their child had an atopic condition, frequent or severe headaches, a parent with less-than-excellent emotional health, or experienced frequent parental anger. Inadequate sleep in both age groups was associated with parental report that their child usually or always displayed depressive symptomatology, family disagreements involved heated arguing, or parental concern that the child was not always safe at home, at school, or in their neighborhood. CONCLUSIONS: Approximately 15 million American children are affected by inadequate sleep. Primary care providers should routinely identify and address inadequate sleep and its associated health, school, and family factors. PMID- 17272583 TI - Nativity/immigrant status, race/ethnicity, and socioeconomic determinants of breastfeeding initiation and duration in the United States, 2003. AB - OBJECTIVES: Previous research has shown substantial racial/ethnic and socioeconomic disparities in US breastfeeding initiation and duration rates. However, the role of immigrant status in understanding such disparities has not been well studied. In this study we examined the extent to which breastfeeding initiation and duration varied by immigrant status overall and in conjunction with race/ethnicity and socioeconomic status after controlling for other relevant social and behavioral covariates. METHODS: The cross-sectional data for 33121 children aged 0 to 5 years from the 2003 National Survey of Children's Health were used to calculate ever-breastfeeding rates and duration rates at 3, 6, and 12 months by social factors. Multivariate logistic regression was used to estimate relative odds of never breastfeeding and not breastfeeding at 6 and 12 months. RESULTS: More than 72% of mothers reported ever breastfeeding their infants, with the duration rate declining to 52%, 38%, and 16% at 3, 6, and 12 months, respectively. Ever-breastfeeding rates varied greatly among the 12 ethnic immigrant groups included in this analysis, from a low of 48% for native black children with native parents to a high of 88% among immigrant black and white children. Compared with immigrant Hispanic children with foreign-born parents (the least acculturated group), the odds of never breastfeeding were respectively 2.4, 2.9, 6.5, and 2.4 times higher for native children with native parents (the most acculturated group) of Hispanic, white, black, and other ethnicities. Socioeconomic patterns also varied by immigrant status, and differentials were greater in breastfeeding at 6 months. CONCLUSIONS: Immigrant women in each racial/ethnic group had higher breastfeeding initiation and longer duration rates than native women. Acculturation was associated with lower breastfeeding rates among both Hispanic and non-Hispanic women. Ethnic-immigrant and social groups with lower breastfeeding rates identified herein could be targeted for breastfeeding promotion programs. PMID- 17272584 TI - The association of health insurance and continuous primary care in the medical home on vaccination coverage for 19- to 35-month-old children. AB - OBJECTIVE: Our goal was to examine the association of continuous care in the medical home and health insurance on up-to-date vaccination coverage by using data from the National Survey of Children's Health and the National Immunization Survey. METHODS: Interviews were conducted with 5400 parents of 19- to 35-month old children to collect data on demographics and medically-verified vaccinations. Health insurance coverage was categorized as always, intermittently, or uninsured for the previous 12 months. Insurance types were private, public, or uninsured. Having a personal doctor or nurse and receiving preventive health care in either the past 12 or 24 months constituted continuous primary care in the medical home. Children were up-to-date if they received all vaccinations by 19 to 35 months of age (>or=4 doses of diphtheria and tetanus toxoids and pertussis vaccine, >or=3 doses of poliovirus vaccine, >or=1 dose of any measles-containing vaccine, >or=3 doses of Haemophilus influenzae type b vaccine, and >or=3 doses of hepatitis B vaccine). RESULTS: Bivariate analyses revealed children who were always insured had significantly higher vaccination coverage (83%) than those with lapses or uninsured during the past 12 months (75% and 71%, respectively). Those with continuous primary care in the medical home had significantly higher coverage than those who did not (83% vs 75%, respectively). In multivariate analysis, the same pattern of association was observed for insurance status and medical home, but the only statistically significant association was for children of never married mothers who had significantly lower coverage (74%) compared with children of married mothers (84%). CONCLUSIONS: Among children with the same insurance status and continuity of care in the medical home, children of single mothers were less likely to be up-to-date than children of married mothers. Interventions assisting single mothers to obtain preventive care for their children should be a priority. PMID- 17272585 TI - Risk and promotive factors in families, schools, and communities: a contextual model of positive youth development in adolescence. AB - OBJECTIVE: Emerging evidence about optimal youth development highlights the importance of both reducing negative behavior and promoting positive behavior. In our study we tested a contextual model derived from positive youth-development theory by examining the association of family, school, and community risk and promotive factors, with several outcome indices of both positive and negative adolescent development. METHODS: A sample of 42305 adolescents aged 11 to 17 (51% girls) was drawn from the 2003 National Survey of Children's Health. Survey item composites were formed representing promotive and risk factors in the family (eg, closeness, aggression) and school and community (eg, community connectedness, school violence). Outcome composites reflected positive (social competence, health-promoting behavior, self-esteem) and negative (externalizing, internalizing, academic problems) developmental outcomes. Ordinary least squares regression was used to test the overall model. RESULTS: Between 0.10 and 0.50 of the variance in each outcome was explained by the contextual model. Multiple positive family characteristics were related to adolescent social competence and self-esteem, as well as lowered levels of internalizing and externalizing behavior and academic problems. Family communication, rules about television, and parents' own healthy behavior were related to adolescent health-promoting behavior. School and community safety were associated with increased social competence and decreased externalizing behavior. School violence was related to adolescent internalizing and externalizing behavior, as well as academic problems and lower self-esteem. CONCLUSIONS: Our results support the proposition that healthy adolescent development has roots in multiple contexts. Youth who were involved in contexts that provided positive resources from important others (ie, parents, schools, and communities) not only were less likely to exhibit negative outcomes, but also were more likely to show evidence of positive development. These findings provide important implications for intervention and prevention efforts and, more generally, for the promotion of positive, competent, and healthy youth development. PMID- 17272586 TI - The health and well-being of adopted children. AB - OBJECTIVE: We compared the health and well-being of adopted and biological children and examined whether observed differences may be a result of differences between these 2 groups in demographic characteristics and special health care needs. METHODS: The 2003 National Survey of Children's Health was funded by the Maternal and Child Health Bureau, Health Resources and Services Administration, and was conducted as a module of the State and Local Area Integrated Telephone Survey by the National Center for Health Statistics, Centers for Disease Control and Prevention. The nationally representative sample consisted of 102,353 children, including 2903 adopted children. We compared estimates for 31 indicators of health and well-being for adopted and biological children and present adjusted estimates that control for differences in demographic characteristics and special health care needs prevalence. RESULTS: Adopted children are more likely than biological children to have special health care needs, current moderate or severe health problems, learning disability, developmental delay or physical impairment, and other mental health difficulties. However, adopted children are more likely than biological children to have had a preventive medical visit or a combination of preventive medical and dental visits during the previous year, to receive needed mental health care, and to receive care in a medical home; they are more likely to have consistent health insurance coverage, to be read to daily, or to live in neighborhoods that are supportive, and they are less likely to live in households in which someone smokes. These differences between adopted and biological children remain statistically significant even after adjustments for differences in demographic characteristics and the prevalence of special health care needs. CONCLUSION: The results suggest that, although adopted children may have poorer health than biological children, their parents may be doing more to ensure that they have needed health care and supportive environments. PMID- 17272587 TI - Factors associated with not having a personal health care provider for children in Florida. AB - OBJECTIVE: National recommendations by the American Academy of Pediatrics and the National Association of Pediatric Nurse Practitioners promote that all children obtain quality primary care through a consistent medical provider who can better assess, diagnose, and monitor a child's health. The purpose of this article was to identify characteristics of children in Florida without a personal health care provider. METHODS: Florida data (N = 2116) from the 2003 National Survey of Children's Health were analyzed by using bivariate and multivariate methods. The dependent, or outcome, variable was a personal health care provider, defined in the National Survey of Children's Health as a personal doctor or nurse. RESULTS: In Florida, 20.1% of children (0-17 years of age) do not have a personal health care provider compared with 16.7% in the United States. Children at greatest risk are those without health insurance. Other significant risk factors include family poverty up to 100% of federal poverty level, poverty level 100% to 199%, poverty level unknown, poverty level 200% to 399%, children aged 5 to 12 years, children aged 13 to 17 years, and Hispanic ethnicity. All the factors in the Florida model were also significant in the national model. CONCLUSIONS: Lack of a personal health care provider is driven by larger community issues of health insurance, socioeconomic status, and ethnicity, including race, on a national level. To achieve the goal of a personal health care provider for children, a multifaceted approach needs to be considered. Knowing which children are without a personal health care provider provides valuable information for state policy-makers, program planners, and evaluators. PMID- 17272588 TI - The prevalence of violent disagreements in US families: effects of residence, race/ethnicity, and parental stress. AB - CONTEXT: Witnessing domestic violence increases a child's chance of emotional or behavioral problems during childhood and entering abusive relationships in adulthood, even without co-occurring child maltreatment. OBJECTIVE: Our goals were to estimate the prevalence of reported violent disagreements in the homes of US children and to assess prevalence differences by race/ethnicity, residence, and reported parenting stress. PATIENTS AND METHODS: Data were drawn from the 2003 National Survey of Children's Health. Case subjects with unknown gender, race/ethnicity, or residence were excluded, yielding 99660 observations. Disagreements were classified on the basis of how the family deals with serious disagreement. If disagreements involved hitting or throwing, even rarely, the household was categorized as having violent disagreements. Households reporting heated argument and shouting were classified as having heated disagreement. RESULTS: Nationally, 10.3% of children lived in homes with reported violent disagreements. Violent disagreements were most prevalent among black households (15.1%), followed by "other" (12.1%), Hispanic (11.3%), and white (8.6%) households. Urban areas had higher prevalence (10.7%) than did small through large rural counties (8.3%-9.9%). In multinomial logistic analysis, parents living in rural counties were less likely to report violent disagreements compared with those in urban. Black children were more likely to be exposed to both violent and heated disagreements than were white children. Parents reporting high parenting stress had higher odds of violent and heated disagreement than parents reporting less stress. CONCLUSIONS: A substantial number of children are exposed to violent disagreement. Although demographic and cultural factors may also influence disagreement style, parental stress seems instrumental in the development of violent disagreements. Parents who experience difficulty with parenting constitute a high-risk population. Helping parents understand and address child behavior may reduce such stress. PMID- 17272589 TI - Lifetime prevalence of learning disability among US children. AB - OBJECTIVE: Our goal was to examine the lifetime prevalence of learning disability by sociodemographic and family-functioning characteristics in US children, with particular attention paid to the children with special health care needs. METHODS: By using data from the National Survey of Children's Health, we calculated lifetime prevalence of learning disability using a question that asked whether a doctor or other health care or school professional ever told the survey respondent that the child had a learning disability. Children with and those without special health care needs were classified on the basis of how many of 5 definitional criteria for children with special health care needs they met (0-5). Bivariate and multivariate statistical methods were used to assess independent associations of selected sociodemographic and family variables with learning disability. RESULTS: The lifetime prevalence of learning disability in US children is 9.7%. Although prevalence of learning disability is lower among average developing children (5.4%), it still affected 2.7 million children compared with 3.3 million (27.8%) children with special health care needs. As the number of definitional criteria children with special health care needs met increased from 1 to 5, so did the prevalence of learning disability (15.0%, 27.1%, 41.6%, 69.3%, and 87.8%, respectively). In the adjusted logistic regression model, in addition to the number of definitional criteria the children met, variables associated with the increased odd ratios of learning disability were lower education, all categories of poverty <300% of the federal poverty level, being male, increasing age, having a 2-parent stepfamily or other family structure, being adopted, presence of a smoker, respondent's higher responses on aggravation in parenting scale, sharing ideas with the child less than very well, and never, rarely, or sometimes discussing serious disagreements calmly. CONCLUSIONS: Although more than half of lifetime prevalence of learning disability occurred in children with special health care needs, it is a significant morbidity in average-developing children as well. Learning disabilities represent important comorbidities among children with special health care needs. PMID- 17272590 TI - A multilevel study of the associations between economic and social context, stage of adolescence, and physical activity and body mass index. AB - OBJECTIVE: Prevention efforts targeting adolescent risk behavior have had limited effectiveness, partly because of the reliance on individual-level interventions that do not consider the context within which behavior occurs. In addition, the role of development has not been well studied regarding its possible moderating effects on contextual influences on behavior. The purpose of this study was to examine the influence of economic and social context on the odds of being inactive or having above-normal weight and whether the influence differed on the basis of stage of adolescence. METHODS: Analysis used a subset of adolescents aged 10 to 17 years from the National Survey of Children's Health (n = 37930) from all states and the District of Columbia (n = 51). Dependent variables included physical activity and BMI. State-level economic context was measured by the proportion of families living below 200% of the federal poverty level. Social context was measured by aggregated means of responses to 2 indicators of social capital: mutual aid and social trust. Multilevel modeling was conducted to investigate associations between state-level economic and social context and physical activity and BMI, while controlling for individual sociodemographic characteristics, and whether these associations were dependent on an individual's stage of adolescence. RESULTS: Both state-level mutual aid and social trust were significantly related to the odds of an adolescent not meeting current physical activity recommendations, yet state-level poverty was not. For BMI, all 3 state level variables were significant predictors of having an above-normal BMI. Evidence was found of the moderating influence of stage of adolescence for both outcomes. CONCLUSIONS: These findings point to the need for the inclusion of contextual-level data in surveillance systems assessing risk behavior in adolescents and consideration of the multilevel nature of the growing problem of inactivity and above-normal weight when focusing public health prevention efforts. PMID- 17272591 TI - Associations between breastfeeding practices and young children's language and motor skill development. AB - OBJECTIVES: We examined the associations of breastfeeding initiation and duration with language and motor skill development in a nationally representative sample of US children aged 10 to 71 months. METHODS: Using cross-sectional data on 22399 children from the 2003 National Survey of Children's Health, we examined relationships between breastfeeding practices and children's language and motor skills development. Outcomes were based on each mother's response to questions regarding her level of concern (a lot, a little, not at all) about her child's development of expressive language, receptive language, fine motor skills, and gross motor skills. Breastfeeding data were based on mothers' recall. Methods of variance estimation were applied and multivariate polynomial regression modeling was done to estimate the effects of breastfeeding initiation and duration on children's development after adjustment for confounders. RESULTS: Mean age of the sample was 2.79 years; 67% were non-Hispanic white, 16% were Hispanic, and 9% were non-Hispanic black. Approximately 17% of mothers reported concerns about their child's expressive language development; approximately 10% had receptive language concerns; approximately 6% had concerns about fine motor skills; and 5% reported general motor skills concerns. Multivariate analysis revealed that mothers who initiated breastfeeding were less likely than mothers of never breastfed children to be concerned a lot about their child's expressive and receptive language development and fine and general motor skills. Mothers of children breastfed 3 to 5.9 months were less likely than mothers of never breastfed children to be concerned a lot about their child's expressive and receptive language and fine and general motor skills. CONCLUSIONS: As with all cross-sectional data, results should be interpreted with caution. Our findings suggest breastfeeding may protect against delays in young children's language and motor skill development. Fewer concerns about language and motor skill development were evident for children breastfed >or=3 months, and concerns generally decreased as breastfeeding continued >or=9 months. PMID- 17272592 TI - National estimates and factors associated with medication treatment for childhood attention-deficit/hyperactivity disorder. AB - OBJECTIVE: In this study we identified child and family-level characteristics that were associated with medication treatment for attention deficit/hyperactivity disorder using nationally representative survey data. METHODS: National Survey of Children's Health data from 79264 youth 4 to 17 years of age were used. Data were weighted to adjust for the complex survey design of the National Survey of Children's Health. Gender-specific logistic regression models were generated to identify child and family-level characteristics that were collectively associated with current medication status among youth with a reported diagnosis of attention-deficit/hyperactivity disorder. RESULTS: Nationally, 7.8% of youth aged 4 to 17 years had a reported attention deficit/hyperactivity disorder diagnosis, and 4.3% had both a disorder diagnosis and were currently taking medication for the disorder. Current medication treatment among youth with attention-deficit/hyperactivity disorder was associated with white race, younger age, English spoken in the home, health care coverage, a health care contact within the last year, and reported psychological difficulties. Gender-specific logistic regression models revealed that, together, younger age, higher income, health care coverage, having psychological difficulties, and a health care contact in the past year were associated with medication use among boys with attention-deficit/hyperactivity disorder. Among girls with the disorder, younger age, psychological difficulties, fair-to-poor paternal mental health status, and a health care contact within the last year were collectively associated with current medication use. CONCLUSIONS. Regardless of gender, younger age, the presence of psychological difficulties, and a recent health care contact were significantly associated with medication treatment for attention-deficit/hyperactivity disorder. However, additional health care access and income variables among boys and paternal mental health status among girls represented gender-specific factors that were also associated with medication treatment for the disorder. Future studies should characterize how and when the burden associated with attention-deficit/hyperactivity disorder leads to treatment, support, or services for this prevalent and impairing neurobehavioral disorder. PMID- 17272593 TI - Pediatric telephone call centers: how do they affect health care use and costs? AB - OBJECTIVES: After-hours call centers have been shown to provide appropriate triage with high levels of parental and provider satisfaction. However, few data are available on the costs and outcomes of call centers from the perspective of the health care system. With this study we sought to determine these outcomes. METHODS: Parents who called the Pediatric After-hours Call Center at the Children's Hospital of Denver from March 19, 2004, to April 19, 2004, were asked an open-ended question before triage: "We would like to know, what you would have done if you could not have called our call center this evening/today?" RESULTS: The response rate for the survey was 77.8% (N = 8980). Parents reported that they would have (1) gone to an emergency department or urgent care facility (46%), (2) treated the child at home (21%), (3) called a physician's office the next day (12%), (4) asked another person for advice (13%), (5) consulted a written source (2%), or (6) other (7%). Of the 46% of callers who would have sought emergent care, only 13.5% subsequently were given an urgent disposition by the call center. Fifteen percent of cases in which the parents would have stayed at home were given an urgent disposition by nurses. Assuming that all callers followed the advice provided, the estimated savings per call, based on local costs, was 42.61 dollars per call. Savings based on Medical Expenditure Panel Survey national payment data were 56.26 dollars per call. CONCLUSIONS: Two thirds of the cases in which parents reported initial intent to go to an emergency department or urgent care facility were not deemed urgent by the call center, whereas 15% of calls from parents who intended to stay home were deemed urgent. If call-center triage recommendations were followed in even half of all cases, then these results would translate into substantial cost savings for the health care system. PMID- 17272595 TI - Effect of long-term steroids on cough efficiency and respiratory muscle strength in patients with Duchenne muscular dystrophy. AB - OBJECTIVE: The objective of this study was to determine whether long-term steroid therapy is associated with increased peak cough flow in patients with Duchenne muscular dystrophy and to determine which pulmonary function test variable is most predictive of peak cough flow. METHODS: In this case-control study, the medical charts of patients who had Duchenne muscular dystrophy and had pulmonary function tests at our institution in the previous 2 years were examined. Steroid treated patients were on therapy for at least 1 year. The measured pulmonary function tests included forced vital capacity, maximum expiratory pressure, maximum inspiratory pressure, maximum voluntary ventilation, and peak cough flow. Multiple linear regression analysis was used to determine which pulmonary function test measure was most predictive of peak cough flow and assess the influence of steroid treatment and patient age on peak cough flow. RESULTS: Ten steroid-treated and 25 untreated patients were analyzed. Peak cough flow and maximum expiratory pressure were significantly higher in the steroid-treated patients. Each of the pulmonary function test variables was significantly associated with peak cough flow. The linear model that had the highest adjusted r2 value included only 2 variables: maximum voluntary ventilation and steroid treatment, demonstrating that steroid-treated patients had peak cough flow values that were 27 L/min higher than the untreated patients. The interaction between maximum voluntary ventilation and steroid was not statistically significant, suggesting that the steroid-associated increase in peak cough flow was approximately constant over the observed range of maximum voluntary ventilation values. The effects of maximum voluntary ventilation and treatment group on peak cough flow were not confounded with the patient age. CONCLUSIONS: Long-term steroid therapy is associated with improved peak cough flow and respiratory muscle strength in patients with Duchenne muscular dystrophy. Maximum voluntary ventilation may be a useful predictor of lung function in Duchenne muscular dystrophy. PMID- 17272594 TI - Longitudinal relationship between television viewing and leisure-time physical activity during adolescence. AB - OBJECTIVE: The goal was to examine the longitudinal associations of changes in television viewing and other sources of sedentary behavior with changes in leisure-time moderate/vigorous physical activity in adolescence. METHODS: We studied a cohort of 6369 girls and 4487 boys who were 10 to 15 years of age in 1997. During each of 4 years of follow-up assessments, participants self-reported their weekly hours of television viewing. By using a seasonal questionnaire, we also obtained detailed information on physical activities over the previous year, from which we calculated total leisure-time moderate/vigorous physical activity. We performed linear regression analyses to assess the longitudinal associations between 1-year changes in television viewing and 1-year changes in leisure-time moderate/vigorous physical activity during the same year, using data from 1997 through 2001. RESULTS: One-year changes (mean +/- SD) were -0.13 +/- 7.2 hours/week for leisure-time moderate/vigorous physical activity, -0.55 +/- 7.0 hours/week for television viewing, and -1.02 +/- 11.0 hours/week for total sedentary behaviors. In longitudinal models adjusted for age, age2, gender, race/ethnicity, Tanner stage, menarche (in girls), baseline physical activity, and baseline television viewing, we found no substantive relationship between year-to-year changes in television viewing and changes in leisure-time moderate/vigorous physical activity (0.03 hours/week, for each 1-hour/week change in television viewing). There were no material associations in age or gender subgroups. CONCLUSIONS: In this longitudinal study, changes in television viewing were not associated with changes in leisure-time moderate/vigorous physical activity. Our findings suggest that television viewing and leisure-time physical activity are separate constructs, not functional opposites. PMID- 17272596 TI - Repeat urine cultures in children who are admitted with urinary tract infections. AB - OBJECTIVE: Urinary tract infections are a common cause of hospitalization in the pediatric population. Hospitalization for urinary tract infections in children usually involves intravenous antibiotics, invasive methods of obtaining sterile urine specimens, and imaging studies to assess the anatomy of the urinary system. The objective of this study was to determine the frequency of positive repeat urine cultures that are obtained after 2 days of antibiotics among pediatric inpatients who are admitted with diagnosed or suspected infections of the urinary tract. METHODS: A retrospective survey was conducted of all pediatric patients (< or = 18 years of age) who were admitted to Elmhurst Hospital in Queens, New York, with a suspected or diagnosed urinary infection from December 1998 through December 2004. Results of repeat urine cultures that were obtained after 2 days of antibiotics were abstracted from a computerized medical charts database. Nominal data analysis was used to establish the frequency of positive repeat urine cultures. RESULTS: A total of 328 (54.8%) of 599 eligible admissions met inclusion criteria. Of these 328 admissions, only 1 (0.3%) repeat urine culture was positive after 2 days of antimicrobial therapy. CONCLUSIONS: Positive repeat urine cultures after 2 days of antibiotics are exceedingly rare. Elimination of mandatory "proof-of-bacteriologic-cure" benchmarks before hospital discharge is supported by this study. PMID- 17272597 TI - Impact of prenatal cocaine exposure on child behavior problems through school age. AB - OBJECTIVE: We examined the trajectory of childhood behavior problems after prenatal cocaine exposure. METHODS: The Maternal Lifestyle Study, a longitudinal cohort study, enrolled children between 1993 and 1995 at 4 centers. Prenatal cocaine exposure was determined from mothers who admitted use and/or meconium results. Exposed children were matched with a group of nonexposed children within site and by gestational age, gender, race, and ethnicity. The study began at the 1-month corrected age with a total of 1388 children enrolled. A total of 1056 were assessed for internalizing, externalizing, and total behavior problems at ages 3, 5, and 7 years using the Child Behavior Checklist. Longitudinal hierarchical linear models were used to determine the effect of prenatal cocaine exposure on behavior problem trajectories while controlling for other prenatal exposures; time-varying covariates, including ongoing caregiver use of legal and illegal substances; demographic factors; family violence; and caregiver psychological distress. RESULTS: High prenatal cocaine exposure was associated with the trajectory of internalizing, externalizing, and total behavior problems; these effects were independent of and less than the significant combined effect of prenatal and postnatal tobacco and alcohol exposures. Caregiver depression and family violence had independent negative influence on all behavior outcomes. CONCLUSIONS: Prenatal cocaine exposure has a negative impact on the trajectories of childhood behavior outcomes. When they co-occur with prenatal cocaine exposure, prenatal and postnatal tobacco and alcohol exposures have added negative effects on behavior outcomes. PMID- 17272598 TI - Diphtheria, pertussis, poliomyelitis, tetanus, and Haemophilus influenzae type b vaccinations and risk of eczema and recurrent wheeze in the first year of life: the KOALA Birth Cohort Study. AB - OBJECTIVES: Among potential etiologic factors for atopic manifestations, infant vaccinations have recently been discussed. We evaluated in a prospective design whether infants who were unvaccinated or vaccinated according to incomplete vaccination schedules in the first 6 months of age were at decreased risk for eczema and recurrent wheeze in the first year of life. METHODS: Information on vaccinations against diphtheria, pertussis, poliomyelitis, tetanus; Haemophilus influenzae type b vaccine; and eczema and recurrent wheeze was collected by repeated questionnaires in 2764 families participating in the KOALA Birth Cohort Study in The Netherlands. A standard vaccination schedule referred to 3 diphtheria, pertussis, poliomyelitis, tetanus, and Haemophilus influenzae type b vaccinations in the first 6 months with the first given in months 1 to 3; an incomplete vaccination schedule was defined as any other vaccination schedule. Exclusion criteria were prematurity (gestational age <37 weeks) and congenital abnormalities related to immunity (such as Down syndrome). Multiple logistic regression models were fitted to adjust for confounding factors. RESULTS: During the first year of life, the incidence of eczema was 23% (584 of 2537 infants) and of recurrent wheeze, the incidence was 8.5% (203 of 2402 infants). At age 6 months, 1969 (77%) of 2545 infants had been vaccinated according to a standard schedule, 393 (15%) vaccinated according to an incomplete schedule, and 182 (7%) never vaccinated. Compared with infants with standard vaccination schedules, infants with incomplete schedules did not differ significantly in eczema risk or recurrent wheeze. This was also true for infants who had never been vaccinated. CONCLUSION: This study shows that the risk of eczema or recurrent wheeze at 1 year of age does not differ between infants with different vaccination status at the age of 6 months. PMID- 17272599 TI - Explaining change in quality of life of children and adolescents with anorectal malformations or Hirschsprung disease. AB - OBJECTIVES: The purpose of this work was to examine changes in quality of life, disease-specific functioning, and psychosocial competencies of children and adolescents (8-16 years of age) with anorectal malformations or Hirschsprung disease and to identify predictors of change in quality of life by testing an explanatory model in which background variables explained changes in quality of life via changes in disease-specific functioning and psychosocial competencies. METHODS: Questionnaires were administered to 129 patients with anorectal malformations and 121 patients with Hirschsprung disease within a 3-year interval. Clinical and sociodemographic background variables were measured on the first occasion. Quality of life (physical and mental), disease-specific functioning (defecation-related), and psychosocial competencies (self-esteem, athletic competencies, and school attitude) were measured on both occasions. RESULTS: Patients improved in disease-specific functioning and mental quality of life. Changes in quality of life were indeed explained by the explanatory model. Among other things, the results indicated that patients with a severe form of the disease or with additional congenital diseases showed worsening of school attitude, which in turn affected change in mental quality of life negatively. CONCLUSIONS: Children and adolescents with anorectal malformations or Hirschsprung disease reported better quality of life over time. To improve and maintain an optimal level of children's and adolescents' quality of life, it is important to direct treatment both to reducing symptoms and enhancing psychosocial competencies, in particular by paying attention to school attitude. PMID- 17272600 TI - Issues in estimating the prevalence of fetal alcohol syndrome: examination of 2 counties in New York State. AB - OBJECTIVE: Two demographically similar counties included in the New York Fetal Alcohol Syndrome Surveillance Network had very different prevalence rates. This study examined the components of the surveillance in an attempt to discover the reasons for this discrepancy. METHODS: Erie County and Monroe County were the 2 most populous counties included in the New York Fetal Alcohol Syndrome Surveillance Network. Erie County includes Buffalo, the second largest city in New York State, and Monroe County includes Rochester, the third largest city. Multiple sources of ascertainment included birth defect surveillance systems, genetic clinics, and early intervention programs. The case definition was based on the Institute of Medicine criteria of an abnormality in each of the following 3 areas: facial features, central nervous system, and growth. RESULTS: Children born in Erie County or Monroe County between 1995 and 1999 were included. The fetal alcohol syndrome prevalence rates in these 2 counties were 0.90 cases per 1000 births and 0.21 cases per 1000 births, respectively. The 2 counties were demographically similar and had similar rates of binge drinking among women of childbearing age. There was less participation in the surveillance system by sources in Monroe County. Erie County had a very active clinician with a specialized fetal alcohol syndrome clinic. CONCLUSIONS: The participation of clinicians in one county, especially one with expertise in fetal alcohol syndrome, was the most likely explanation for the differences in prevalence rates between the counties. PMID- 17272601 TI - Guardianship planning among HIV-infected parents in the United States: results from a nationally representative sample. AB - OBJECTIVE: The purpose of this work was to determine the rates and predictors of guardianship planning and preferred guardians among HIV-infected parents. PARTICIPANTS AND METHODS: Data were analyzed from interviews with 222 unmarried parents (who had 391 children) from a nationally representative sample of HIV infected adults receiving health care. Outcome measures included parental report on the level of guardianship planning and on who their preferred guardian for each child was. Level of guardianship planning was categorized as follows: (1) parent had not identified a guardian; (2) parent had identified a guardian, but the guardian had not agreed; (3) identified guardian had agreed; and (4) legal documentation of guardianship plan was complete. We conducted bivariate and ordered logistic regression analyses on the level of guardianship planning and multinomial logistic regression on identification of preferred guardians. RESULTS: Twelve percent of unmarried HIV-infected parents had not identified a guardian; 6% had identified a guardian but gone no further; 53% said the identified guardian had agreed; and 28% had prepared legal documentation. The preferred guardians included other biological parents (17%), spouse/partners who were not biological parents (2%), grandparents (36%), other relatives (34%), friends (7%), unrelated adoptions (1%), and others (3%). Parents with the lowest CD4 counts and parents living without other adults were more likely to have completed the guardianship planning process. Nonrelatives were most often preferred by mothers and parents with higher CD4 counts; grandparents were most often preferred by younger parents and parents who prefer speaking Spanish. CONCLUSIONS: Pediatricians and others who take care of children with HIV-infected parents may be able to provide counseling and referrals for guardianship planning. PMID- 17272602 TI - A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease? AB - OBJECTIVE: The purpose of this study was to review the experience with herpes simplex encephalitis at the Hospital for Sick Children over the past 12 years. METHODS: All patients who were admitted to our institution with acute encephalitis between January 1994 and December 2005 were enrolled prospectively in an encephalitis registry. Children from the registry with herpes simplex encephalitis were included in this study; we detailed the clinical presentations, laboratory findings, electroencephalographic findings, diagnostic imaging findings, treatments, and outcomes for all cases. RESULTS: Of 322 cases of acute encephalitis, 5% were caused by herpes simplex virus. Initially negative herpes simplex virus cerebrospinal fluid polymerase chain reaction results were found in 2 cases (13%), but results became positive in repeat cerebrospinal fluid analyses. Classic clinical presentations were seen in 75% of cases, cerebrospinal fluid pleocytosis was found in 94%, elevated cerebrospinal fluid protein levels were found in 50%, electroencephalographic changes were observed in 94%, and diagnostic imaging abnormalities were noted in 88%. All patients were treated with intravenous acyclovir. Neurologic sequelae occurred in 63% of cases, including seizures in 44% and developmental delays in 25%. There were no deaths in this study group. CONCLUSIONS: Herpes simplex encephalitis continues to be associated with poor long-term neurologic outcomes despite appropriate therapy. Cerebrospinal fluid polymerase chain reaction results may be negative early in the course of herpes simplex encephalitis; therefore, repeat cerebrospinal fluid analysis should be considered if herpes simplex encephalitis is suspected. Atypical forms of herpes simplex virus central nervous system disease may occur in children. PMID- 17272603 TI - Risk factors for deformational plagiocephaly at birth and at 7 weeks of age: a prospective cohort study. AB - OBJECTIVE: The purpose of this work was to identify risk factors for deformational plagiocephaly within 48 hours of birth and at 7 weeks of age. PATIENTS AND METHODS: This was a prospective cohort study in which 380 healthy neonates born at term in Bernhoven Hospital in Veghel were followed at birth and at 7 weeks of age. Data regarding obstetrics, sociodemographics, asymmetry of the skull, anthropometrics, motor development, positioning, and care factors related to potentially provoking deformational plagiocephaly were gathered, with special interest for putative risk factors. The main outcome measure at birth and at 7 weeks of age was deformational plagiocephaly, assessed using the plagiocephalometry parameter oblique diameter difference index, a ratio variable, calculated as the longest divided by the shortest oblique diameter of the skull x 100%. A cutoff point of > or = 104% was used to indicate severe deformational plagiocephaly. RESULTS: Only in 9 of 23 children who presented deformational plagiocephaly at birth was deformational plagiocephaly present at follow-up, whereas in 75 other children, deformational plagiocephaly developed between birth and follow-up. At birth, 3 of 14 putative risk factors were associated with severe flattening of the skull: gender, birth rank, and brachycephaly. At 7 weeks of age, 8 of 28 putative risk factors were associated with severe flattening: gender, birth rank, head position when sleeping, position on chest of drawers, method of feeding, positioning during bottle-feeding, and tummy time when awake. Early achievement of motor milestones was a protective factor for developing deformational plagiocephaly. Deformational plagiocephaly at birth was not a predictor for deformational plagiocephaly at 7 weeks of age. There was no significant relation between supine sleeping and deformational plagiocephaly. CONCLUSIONS: Three determinants were associated with an increased risk of deformational plagiocephaly at birth: male gender, first-born birth rank, and brachycephaly. Eight factors were associated with an increased risk of deformational plagiocephaly at 7 weeks of age: male gender, first-born birth rank, positional preference when sleeping, head to the same side on chest of drawers, only bottle feeding, positioning to the same side during bottle feeding, tummy time when awake < 3 times per day, and slow achievement of motor milestones. This study supports the hypothesis that specific nursing habits, as well as motor development and positional preference, are primarily associated with the development of deformational plagiocephaly. Earlier achievement of motor milestones probably protects the child from developing deformational plagiocephaly. Implementation of practices based on this new evidence of preventing and diminishing deformational plagiocephaly in child health care centers is very important. PMID- 17272604 TI - Prenatal alcohol exposure and gender differences in childhood mental health problems: a longitudinal population-based study. AB - OBJECTIVES: High levels of alcohol use during pregnancy can lead to adverse physical and neurodevelopmental outcomes in children. It remains uncertain whether there is a safe level of drinking during pregnancy. In this study we investigate whether very low levels of alcohol consumption (<1 drink per week) are independently associated with childhood mental health problems (assessed at 3 time points between ages 4 and 8 years) and whether these effects are moderated by gender. We expected that only higher levels of alcohol consumption would be associated with later mental health problems and that any associations might be more readily detectable in boys. METHODS: This prospective, population-based study used data from the Avon Longitudinal Study of Parents and Children. We investigated the relationship between self-reports of the amount and frequency of alcohol use in the first trimester and the presence of clinically significant mental health (behavioral and emotional) problems at 47 and 81 months (parental report: n = 9086 and 8046, respectively) and at 93 to 108 months (teacher report: n = 5648). RESULTS: After controlling for a range of prenatal and postnatal factors, the consumption of <1 drink per week during the first trimester was independently associated with clinically significant mental health problems in girls at 47 months. This gender-specific association persisted at 81 months and was confirmed by later teacher ratings. CONCLUSIONS: Very low levels of alcohol consumption during early pregnancy may have a negative and persistent effect on mental health outcomes. Given the lack of a clear dose-response relationship and unexpected gender effects, these findings should be considered preliminary and need additional investigation. PMID- 17272605 TI - Factors associated with the diagnosis of neurodevelopmental disorders: a population-based longitudinal study. AB - OBJECTIVES: We investigated the occurrence of newly diagnosed mental retardation, attention-deficit/hyperactivity disorder, and autism and sociodemographic factors associated with their distribution in Taiwan, and we examined urbanicity- and socioeconomic status-associated differences in the age at first diagnosis. METHODS: The data for this study were derived from the 1996-2004 National Health Insurance Research Database in Taiwan. Approximately 1.8 million beneficiaries born between 1996 and 2001 were identified, with follow-up periods ranging from 3 to 8 years. RESULTS: Each of the 3 neurodevelopmental disorders had distinct incidence rates and associated factors. For example, as compared with the birth years of 1996-1999, the rate of autism increased 14% during the period 2000-2004, whereas the rate of newly diagnosed mental retardation decreased 42% to 50% over the same period. An elevated incidence rate for attention-deficit/hyperactivity disorder and autism was observed in later birth cohorts. The risk of receiving a diagnosis of mental retardation for children in rural areas and of lower socioeconomic status was reduced in early childhood and increased in school ages as compared with their urban and higher socioeconomic status counterparts. CONCLUSIONS: Variation in the rate of newly diagnosed mental retardation, attention-deficit/hyperactivity disorder, and autism among children in Taiwan depended on age, birth year, period, and socioeconomic status. The extent of the association linking age with the first diagnosis of mental retardation varies across different urbanicity level and socioeconomic status. PMID- 17272606 TI - Grandmother and parent influences on child self-esteem. AB - OBJECTIVES: This study tests a model of intergenerational influences on childhood self-esteem that proposes paths from grandmothers' drug problems to grandchildren's self-esteem via parents' drug problems and parental adaptive child rearing and from grandmothers' maternal acceptance to grandchildren's self esteem via parents' unconventionality and adaptive child rearing. METHODS: This longitudinal study uses data obtained from interviews with a New York City sample of black and Puerto Rican children (N = 149) and 1 of their parents and from mailed questionnaires or comparable interviews with those parents' mothers. Structural equation modeling was used to test the proposed model. RESULTS: The LISREL analysis found that, with 3 exceptions, all of the hypothesized paths were significant. The total effects analysis indicated that parents' adaptive child rearing was the strongest latent construct, a finding that was consistent with this construct's proximal position in the model. CONCLUSIONS: This study suggests that mothers' drug problems are not just near-term risks for their children, but also pose long-term risks for their children's future functioning as parents and thereby for their grandchildren. The relative strength of parents' adaptive child rearing in this intergenerational model indicates that this area should be the focus of therapeutic intervention efforts, but addressing future grandmothers' drug problems may have positive effects on multiple generations. PMID- 17272607 TI - Impact of full mental health and substance abuse parity for children in the Federal Employees Health Benefits Program. AB - OBJECTIVE: The Federal Employees Health Benefits Program implemented full mental health and substance abuse parity in January 2001. Evaluation of this policy revealed that parity increased adult beneficiaries' financial protection by lowering mental health and substance abuse out-of-pocket costs for service users in most plans studied but did not increase rates of service use or spending among adult service users. This study examined the effects of full mental health and substance abuse parity for children. METHODS: Employing a quasiexperimental design, we compared children in 7 Federal Employees Health Benefits plans from 1999 to 2002 with children in a matched set of plans that did not have a comparable change in mental health and substance abuse coverage. Using a difference-in-differences analysis, we examined the likelihood of child mental health and substance abuse service use, total spending among child service users, and out-of-pocket spending. RESULTS: The apparent increase in the rate of children's mental health and substance abuse service use after implementation of parity was almost entirely due to secular trends of increased service utilization. Estimates for children's mental health and substance abuse spending conditional on this service use showed significant decreases in spending per user attributable to parity for 2 plans; spending estimates for the other plans were not statistically significant. Children using these services in 3 of 7 plans experienced statistically significant reductions in out-of-pocket spending attributable to the parity policy, and the average dollar savings was sizeable for users in those 3 plans. In the remaining 4 plans, out-of-pocket spending also decreased, but these decreases were not statistically significant. CONCLUSIONS: Full mental health and substance abuse parity for children, within the context of managed care, can achieve equivalence of benefits in health insurance coverage and improve financial protection without adversely affecting health care costs but may not expand access for children who need these services. PMID- 17272608 TI - New York State cystic fibrosis consortium: the first 2.5 years of experience with cystic fibrosis newborn screening in an ethnically diverse population. AB - OBJECTIVE: The purpose of this work was to report on the first 2.5 years of newborn screening for cystic fibrosis in New York. METHODS: Directors of the 11 New York cystic fibrosis centers were asked to provide mutation data, demographic data, and selected laboratory results for each patient diagnosed by newborn screening and followed at their center. Summary data were also submitted from the New York newborn screening laboratory on the total number of patients screened, the number of positive screens, and the number of patients that were lost to follow-up. A second survey was submitted by each center regarding the availability of genetic counseling services at the center. RESULTS: A total of 106 patients with cystic fibrosis were diagnosed through newborn screening in the first 2.5 years and followed at the 11 Cystic Fibrosis Foundation-sponsored cystic fibrosis care centers in New York. Two screen-negative infants were subsequently diagnosed with cystic fibrosis when symptoms developed. The allele frequency of deltaF508 was 57.4%, which is somewhat lower than the allele frequency of deltaF508 in the US cystic fibrosis population of 70%. There were 90 non-Hispanic white (84%), 12 Hispanic, 2 Asian, and 1 black infants diagnosed with cystic fibrosis during this period. Five patients were diagnosed secondary to a positive screen based on a high immunoreactive trypsinogen and no mutations. CONCLUSIONS: Newborn screening for cystic fibrosis has been effectively conducted in New York using a unique screening algorithm that was designed to be inclusive of the diverse racial makeup of the state. However, this algorithm results in a high false-positive rate, and a large number of healthy newborns are referred for confirmatory sweat tests and genetic counseling. This experience indicates that it would be helpful to convene a working group of cystic fibrosis newborn screening specialists to evaluate which mutations should be included in a newborn screening panel. PMID- 17272609 TI - Guidelines for implementation of cystic fibrosis newborn screening programs: Cystic Fibrosis Foundation workshop report. AB - Newborn screening for cystic fibrosis offers the opportunity for early intervention and improved outcomes. This summary, resulting from a workshop sponsored by the Cystic Fibrosis Foundation to facilitate implementation of widespread high quality cystic fibrosis newborn screening, outlines the steps necessary for success based on the experience of existing programs. Planning should begin with a workgroup composed of those who will be responsible for the success of the local program, typically including the state newborn screening program director and cystic fibrosis care center directors. The workgroup must develop a screening algorithm based on program resources and goals including mechanisms available for sample collection, regional demographics, the spectrum of cystic fibrosis disease to be detected, and acceptable failure rates of the screen. The workgroup must also ensure that all necessary guidelines and resources for screening, diagnosis, and care be in place prior to cystic fibrosis newborn screening implementation. These include educational materials for parents and primary care providers; systems for screening and for providing diagnostic testing and counseling for screen-positive infants and their families; and protocols for care of this unique population. This summary explores the benefits and risks of various screening algorithms, including complex situations that can occur involving unclear diagnostic results, and provides guidelines and sample materials for state newborn screening programs to develop and implement high quality screening for cystic fibrosis. PMID- 17272610 TI - Gabapentin successfully manages chronic unexplained irritability in children with severe neurologic impairment. AB - Neurologically impaired children have an increased frequency of recurrent pain and irritability that persist in some despite comprehensive evaluation and management of possible pain sources. We hypothesized that visceral hyperalgesia was a source of chronic unexplained irritability and report the outcome of gabapentin treatment in 9 severely neurologically impaired children. Caregivers reported marked improvement after treatment ranging from 3 months to 3 years. Nystagmus in 1 child was the only noted adverse effect. Visceral hyperalgesia may be a source of unexplained irritability in the neurologically impaired child. Symptoms may improve with gabapentin treatment. PMID- 17272611 TI - Adolescents' reported consequences of having oral sex versus vaginal sex. AB - OBJECTIVE: The present study examined whether adolescents' initial consequences of sexual activity differ according to type of sexual activity and gender. METHODS: Surveys were administered to 618 adolescents recruited from 2 public high schools in the autumn of ninth grade (2002) and at 6-month intervals until the spring of tenth grade (2004). Analyses were limited to the 275 adolescents (44%) who reported engaging in oral sex and/or vaginal sex at any assessment. Participants were 14 years of age at study entry, 56% female, and of diverse socioeconomic and ethnic backgrounds. RESULTS: In comparison with adolescents who engaged in oral sex and/or vaginal sex, adolescents who engaged only in oral sex were less likely to report experiencing a pregnancy or sexually transmitted infection, feeling guilty or used, having their relationship become worse, and getting into trouble with their parents as a result of sex. Adolescents who engaged only in oral sex were also less likely to report experiencing pleasure, feeling good about themselves, and having their relationship become better as a result of sex. Boys were more likely than girls to report feeling good about themselves, experiencing popularity, and experiencing a pregnancy or sexually transmitted infection as a result of sex, whereas girls were more likely than boys to report feeling bad about themselves and feeling used. CONCLUSIONS: Adolescents experience a range of social and emotional consequences after having sex. Our findings have implications for clinical practice and public health campaigns targeted toward youth. PMID- 17272613 TI - Unwanted and wanted exposure to online pornography in a national sample of youth Internet users. AB - OBJECTIVE: The goal was to assess the extent of unwanted and wanted exposure to online pornography among youth Internet users and associated risk factors. METHODS: A telephone survey of a nationally representative sample of 1500 youth Internet users aged 10 to 17 years was conducted between March and June 2005. RESULTS: Forty-two percent of youth Internet users had been exposed to online pornography in the past year. Of those, 66% reported only unwanted exposure. Multinomial logistic regression analysis was used to compare youth with unwanted exposure only or any wanted exposure with those with no exposure. Unwanted exposure was related to only 1 Internet activity, namely, using file-sharing programs to download images. Filtering and blocking software reduced the risk of unwanted exposure, as did attending an Internet safety presentation by law enforcement personnel. Unwanted exposure rates were higher for teens, youth who reported being harassed or sexually solicited online or interpersonally victimized offline, and youth who scored in the borderline or clinically significant range on the Child Behavior Checklist subscale for depression. Wanted exposure rates were higher for teens, boys, and youth who used file-sharing programs to download images, talked online to unknown persons about sex, used the Internet at friends' homes, or scored in the borderline or clinically significant range on the Child Behavior Checklist subscale for rule-breaking. Depression also could be a risk factor for some youth. Youth who used filtering and blocking software had lower odds of wanted exposure. CONCLUSIONS: More research concerning the potential impact of Internet pornography on youth is warranted, given the high rate of exposure, the fact that much exposure is unwanted, and the fact that youth with certain vulnerabilities, such as depression, interpersonal victimization, and delinquent tendencies, have more exposure. PMID- 17272612 TI - Systolic blood pressure in childhood predicts hypertension and metabolic syndrome later in life. AB - OBJECTIVE: The goal was to link hypertension and the metabolic syndrome in adulthood directly to blood pressures measured decades earlier for the same individuals as children and to establish criterion values for blood pressure that predict hypertension and the metabolic syndrome later in life. METHODS: We analyzed serial data for 240 men and 253 women in the Fels Longitudinal Study. We derived age- and gender-specific childhood blood pressures that predict hypertension and the metabolic syndrome in adulthood, and we validated these criterion values in a larger sample. RESULTS: Blood pressure diverged between adults with and without the metabolic syndrome beginning at age 5 for boys and age 8 for girls. The odds ratios for developing hypertension at > or = 30 years of age ranged from 1.1 for 14- to 18-year-old boys to 3.8 for 5- to 7-year-old boys and from 2.7 for 8- to 13-year-old girls to 4.5 for 5- to 7-year-old girls, if their blood pressure exceeded criterion values at a single examination in childhood. The corresponding odds ratios for the metabolic syndrome, with or without hypertension, ranged from 1.2 for 14- to 18-year-old boys to 2.6 for 8- to 13-year-old boys and from 1.5 for 14- to 18-year-old girls to 3.1 for 5- to 7 year-old girls. The relative risk of adult hypertension ranged from 1.5 to 3.8 for boys and from 1.5 to 4.7 for girls, and that of the metabolic syndrome ranged from 1.1 to 1.8 for boys and from 1.2 to 5.6 for girls. These relative risks varied directly with the number of examinations at which systolic blood pressure exceeded criterion values. CONCLUSION: Children with systolic blood pressures above the criterion values established in this longitudinal study are at increased risk of hypertension and the metabolic syndrome later in life. PMID- 17272614 TI - Physician attitudes regarding breakthrough varicella disease and a potential second dose of varicella vaccine. AB - OBJECTIVE: We assessed physicians' attitudes about the 1-dose varicella vaccination program and whether physicians think a 2-dose recommendation is needed to reduce the risk of breakthrough disease. METHODS: We conducted a national mail survey of a random sample of 550 pediatricians and 550 family physicians from April to June 2005. Physicians who provide outpatient primary care to children < or = 6 years of age were eligible for analysis. RESULTS: Surveys were returned by 727 respondents, for a response rate of 69%; 610 physicians were eligible. Most respondents (94%) recommend routine 1-dose varicella vaccination, and 79% have seen breakthrough disease in the past 5 years (95% of pediatricians and 58% of family physicians). The majority (68%) agreed or strongly agreed that the current burden of breakthrough disease is acceptable. Only 38% (46% of pediatricians and 28% of family physicians) agreed or strongly agreed that a second dose of varicella vaccine is needed to address the burden of breakthrough disease, whereas 40% were neutral. However, if the Advisory Committee on Immunization Practices were to recommend a second dose of varicella vaccine, then 65% of pediatricians and 39% of family physicians would likely follow the recommendation. Most respondents (78%) would be more willing to recommend a second dose if a combination measles-mumps-rubella-varicella vaccine was available. CONCLUSIONS: Pediatricians and family physicians support the 1 dose varicella vaccination program. A new Advisory Committee on Immunization Practices recommendation for a second dose of varicella vaccine for children was issued after the survey (in June 2006). Two of 3 pediatricians and 2 of 5 family physicians stated that they would adopt a 2-dose recommendation in practice; rates of adoption may be bolstered with current availability of measles-mumps rubella-varicella vaccine and harmonization of the varicella vaccination schedule with that of measles-mumps-rubella vaccine. PMID- 17272615 TI - Postnatal dexamethasone therapy and cerebral tissue volumes in extremely low birth weight infants. AB - OBJECTIVE: Our goal was to relate postnatal dexamethasone therapy in extremely low birth weight infants (birth weight of < or = 1000 g) to their total and regional brain volumes, as measured by volumetric MRI performed at term equivalent age. METHODS: Among 53 extremely low birth weight infants discharged between June 1 and December 31, 2003, 41 had high-quality MRI studies; 30 of those infants had not received postnatal steroid treatment and 11 had received dexamethasone, all after postnatal age of 28 days, for a mean duration of 6.8 days and a mean cumulative dose of 2.8 mg/kg. Anatomic brain MRI scans obtained at 39.5 weeks (mean) postmenstrual age were segmented by using semiautomated and manual, pretested, scoring algorithms to generate three-dimensional cerebral component volumes. Volumes were adjusted according to postmenstrual age at MRI. RESULTS: After controlling for postmenstrual age at MRI, we observed a 10.2% smaller total cerebral tissue volume in the dexamethasone-treated group, compared with the untreated group. Cortical tissue volume was 8.7% smaller in the treated infants, compared with untreated infants. Regional volume analysis revealed a 20.6% smaller cerebellum and a 19.9% reduction in subcortical gray matter in the dexamethasone-treated infants, compared with untreated infants. In a series of regression analyses, the reductions in total cerebral tissue, subcortical gray matter, and cerebellar volumes associated with dexamethasone administration remained significant after controlling not only for postmenstrual age but also for bronchopulmonary dysplasia and birth weight. CONCLUSIONS: We identified smaller total and regional cerebral tissue volumes in extremely low birth weight infants treated with relatively conservative regimens of dexamethasone. These volume deficits may be the structural antecedents of neuromotor and cognitive abnormalities reported after postnatal dexamethasone treatment. PMID- 17272617 TI - Special Supplemental Nutrition Program for Women, Infants, and Children and infant feeding practices. AB - OBJECTIVE: This study examined the association between participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and adherence to 4 American Academy of Pediatrics recommendations on infant feeding. METHODS: We used data from the Early Childhood Longitudinal Study-Birth Cohort, which is nationally representative of children born in 2001. We estimated regression models to assess relationships between program participation and adherence to American Academy of Pediatrics recommendations on exclusive breastfeeding and the introduction of infant formula, cow's milk, and solid foods. RESULTS: Regression results indicated that WIC participation was associated with a 5.9-percentage point decrease in the likelihood of exclusive breastfeeding for > or = 4 months and a 1.9-percentage point decrease in the likelihood of exclusive breastfeeding for > or = 6 months. Program mothers were 8.5 percentage points less likely than nonparticipants to adhere to the American Academy of Pediatrics recommendation to delay introduction of infant formula until month 6. Program mothers were 2.5 percentage points more likely than nonparticipants to delay the introduction of cow's milk until month 8. Program participants were 4.5 percentage points less likely than nonparticipants to delay the introduction of solid foods for > or = 4 months. However, the difference between participants and nonparticipants disappeared by month 6. CONCLUSIONS: Results suggest that, although program participants are less likely to breastfeed exclusively than eligible nonparticipants, program-provided infant formula is an important option for mothers who do not breastfeed exclusively. The program faces the challenge to encourage breastfeeding without undermining incentives to follow other recommended infant feeding practices. Recent changes proposed to the food packages by the US Department of Agriculture Food and Nutrition Service are consistent with the goal of increasing adherence to recommended infant feeding practices among participants. PMID- 17272616 TI - Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week. AB - OBJECTIVE: The goals were to identify the blood pressures of extremely low gestational age newborns that prompt intervention, to identify other infant characteristics associated with receipt of therapies intended to increase blood pressure, and to assess the interinstitutional variability in the use of these therapies. METHODS: The cohort included 1507 extremely low gestational age newborns born at 23 weeks to 27 weeks of gestation, at 14 institutions, between March 2002 and August 2004; 1387 survived the first postnatal week. Blood pressures were measured as clinically indicated. Interventions were grouped as any treatment (ie, vasopressor and/or fluid boluses of >10 mL/kg) and vasopressor treatment, and logistic regression analyses were performed. RESULTS: At each gestational age, the lowest mean arterial pressures in treated and untreated infants tended to increase with advancing postnatal age. Infants who received any therapy tended to have lower mean arterial pressures than infants who did not, but uniform thresholds for treatment were not apparent. The proportion of infants receiving any treatment decreased with increasing gestational age from 93% at 23 weeks to 73% at 27 weeks. Treatment nearly always began during the first 24 hours of life. Lower gestational age, lower birth weight, male gender, and higher Score for Neonatal Acute Physiology-II values were associated with any treatment and vasopressor treatment. Institutions varied greatly in their tendency to offer any treatment and vasopressor treatment. Neither the lowest mean arterial pressure on the day of treatment nor other characteristics of the infants accounted for center differences in treatment. CONCLUSIONS: Blood pressure in extremely premature infants not treated for hypotension increased directly with both increasing gestational age and postnatal age. The decision to provide treatment was associated more strongly with the center where care was provided than with infant attributes. PMID- 17272618 TI - Randomized trial of a single repeat dose of prenatal betamethasone treatment in imminent preterm birth. AB - BACKGROUND: A single dose of prenatal betamethasone treatment decreases neonatal morbidity rates when administered within 7 days before preterm delivery. A single repeat dose or booster dose of betamethasone before delivery has been proposed to be effective, but its efficacy has not been subjected to a randomized, blinded trial. METHODS: Women with imminent delivery before 34.0 gestational weeks were eligible if they remained without delivery for >7 days after a single course of betamethasone. After stratification, a single repeat dose of betamethasone (12 mg) or placebo was administered. The primary outcome was survival without respiratory distress syndrome or severe intraventricular hemorrhage (grade 3 or 4). RESULTS: A total of 249 mothers had been enrolled by the time the study was discontinued. All of the 159 infants in the betamethasone group and 167 in the placebo group were born before 36 weeks of gestation. The intact survival rate was unaffected and was lower than anticipated, because the gestational age adjusted incidence of respiratory distress syndrome was higher than the population incidence. The requirement for surfactant therapy in respiratory distress syndrome was increased in the betamethasone group. According to posthoc analysis of the data for 206 infants who were delivered within 1 to 24 hours, the betamethasone booster tended to increase the risk of respiratory distress syndrome and to decrease intact survival rates. CONCLUSIONS: According to this study, a single booster dose of betamethasone just before preterm birth may perturb respiratory adaptation. These results caution against uncontrolled use of a repeat dose of glucocorticoid in high-risk pregnancies. PMID- 17272619 TI - Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. AB - OBJECTIVE: The goal was to test the hypothesis that extremes of PaCO2 during the first 4 days after birth are associated with severe intraventricular hemorrhage (grades 3 and 4). METHODS: A single-center retrospective review of clinical and blood gas data in the first 4 postnatal days for 849 infants with birth weights of 401 to 1250 g was performed. The univariate and multivariate relationships of severe intraventricular hemorrhage with maximal and minimal PaCO2, PaCO2 averaged over time (time-weighted PaCO2), and measures of PaCO2 fluctuation (SD of PaCO2 and difference in PaCO2 [maximum minus minimum]) were assessed. RESULTS: Birth weight (mean +/- SD) was 848 +/- 212 g, and the median gestational age was 26 weeks. Infants with severe intraventricular hemorrhage had higher maximal PaCO2 (median: 72 vs 59 mm Hg) and time-weighted PaCO2 (mean: 49 vs 47 mm Hg) values but lower minimal PaCO2 values (32 vs 37 mm Hg). High PaCO2, low PaCO2, SD of PaCO2, and difference in PaCO2 predicted severe intraventricular hemorrhage, but time-weighted average PaCO2 was not as predictive. CONCLUSIONS: Both extremes and fluctuations of PaCO2 are associated with severe intraventricular hemorrhage. It may be prudent to avoid extreme hypocapnia and hypercapnia during the period of risk for intraventricular hemorrhage. PMID- 17272620 TI - Association of apolipoprotein E genotype and cerebral palsy in children. AB - OBJECTIVES: We tested the hypotheses that apolipoprotein E genotype, in particular carriage of the epsilon4 allele, is more likely to be associated with cerebral palsy and that children with more severe neurologic impairment are more likely to carry this allele. METHODS: In this cross-sectional study, 209 children with cerebral palsy were matched with healthy control subjects according to gender and race. Diagnosis of cerebral palsy was confirmed through physician consultation, medical chart review, and parent interview. Apolipoprotein E genotyping was performed with DNA obtained with buccal swabs. Severity of motor impairment was rated by physical therapists, and occipitofrontal circumference was measured. RESULTS: Compared with gender- and race-matched control subjects, overall risk for cerebral palsy was elevated 3.4-fold among children carrying an epsilon4 allele and was particularly elevated for children with quadriplegia/triplegia. This finding was independent of birth weight. Carriage of the epsilon4 allele was also associated with increased severity of cerebral palsy and with a trend toward increased likelihood for microcephaly. Moreover, children carrying an epsilon2 allele were at greater risk for cerebral palsy. CONCLUSIONS: These data implicate the apolipoprotein E epsilon4 and epsilon2 genotypes as susceptibility factors in determining neurologic outcomes after perinatal brain injury. Additional studies are warranted to establish the role of apolipoprotein E in specific pathogenetic pathways leading to cerebral palsy or poor neurologic outcomes after perinatal brain injury. PMID- 17272621 TI - Neonatal intensive care unit census influences discharge of moderately preterm infants. AB - OBJECTIVE: The timely discharge of moderately premature infants has important economic implications. The decision to discharge should occur independent of unit census. We evaluated the impact of unit census on the decision to discharge moderately preterm infants. DESIGN/METHODS: In a prospective multicenter cohort study, we enrolled 850 infants born between 30 and 34 weeks' gestation at 10 NICUs in Massachusetts and California. We divided the daily census from each hospital into quintiles and tested whether discharges were evenly distributed among them. Using logistic regression, we analyzed predictors of discharge within census quintiles associated with a greater- or less-than-expected likelihood of discharge. We then explored parental satisfaction and postdischarge resource consumption in relation to discharge during census periods that were associated with high proportions of discharge. RESULTS: There was a significant correlation between unit census and likelihood of discharge. When unit census was in the lowest quintile, patients were 20% less likely to be discharged when compared with all of the other quintiles of unit census. In the lowest quintile of unit census, patient/nurse ratio was the only variable associated with discharge. When census was in the highest quintile, patients were 32% more likely to be discharged when compared with all of the other quintiles of unit census. For patients in this quintile, a higher patient/nurse ratio increased the likelihood of discharge. Conversely, infants with prolonged lengths of stay, an increasing Score for Neonatal Acute Physiology II, and minor congenital anomalies were less likely to be discharged. Infants discharged at high unit census did not differ from their peers in terms of parental satisfaction, emergency department visits, home nurse visits, or rehospitalization rates. CONCLUSIONS: Discharges are closely correlated with unit census. Providers incorporate demand and case mix into their discharge decisions. PMID- 17272622 TI - Reduced time in bed and obstructive sleep-disordered breathing in children are associated with cognitive impairment. AB - OBJECTIVE: The purpose of this study was to determine if reduced time in bed as well as the degree of obstructive sleep-disordered breathing predicted the risk of impaired cognitive function in children with adenotonsillar hypertrophy suspected of having obstructive sleep-disordered breathing. DESIGN: We studied 56 children, aged 6 to 12 years, with adenotonsillar hypertrophy referred for suspected obstructive sleep-disordered breathing. Children were given a sleep diary and underwent wrist actigraphy for 6 consecutive days and nights. On day 7, the children were given general cognitive tests, memory tests, and continuous performance tests followed by attended polysomnography that night. Parents completed snoring and behavior questionnaires. RESULTS: Shorter mean time in bed for 6 nights and a history of nightly snoring were highly predictive of lower scores for the vocabulary and similarities cognitive function tests. Children who had a mean time in bed of 557 minutes and did not snore nightly were predicted to have vocabulary and similarities scores more than 1 standard deviation higher than children who had a mean time in bed of 521 minutes and snored nightly. Shorter mean time in bed and the log of the apnea hypopnea index also predicted lower vocabulary and similarities scores. Greater night to night variability in time in bed was significantly predictive of lower vocabulary and similarities scores, but variability was not as predictive as mean time in bed. Neither mean time in bed nor the coefficient of variation of time in bed predicted other cognitive or behavioral scores. CONCLUSIONS: Short or variable time in bed and nightly snoring or higher apnea hypopnea index predicted impaired vocabulary and similarities scores in children with adenotonsillar hypertrophy suspected of having obstructive sleep-disordered breathing. The degree of cognitive impairment attributable to short time in bed and obstructive sleep-disordered breathing is clinically very significant. PMID- 17272623 TI - Persistent diastolic flow reversal in abdominal aortic Doppler-flow profiles is associated with an increased risk of necrotizing enterocolitis in term infants with congenital heart disease. AB - OBJECTIVE: Diastolic runoff in the abdominal aorta, with subsequent circulatory mesenteric insufficiency, has been postulated as a cause of necrotizing enterocolitis in term infants with congenital heart disease. With this study we sought to determine whether Doppler-flow characteristics in the abdominal aorta can predict which infants are at specific risk, independent of gestational age and type of congenital heart disease. PATIENTS AND METHODS: We conducted a case control study of term infants with congenital heart disease and proven necrotizing enterocolitis (n = 18) compared with gestational age-matched and diagnosis-matched control subjects (n = 20). Abdominal aortic Doppler velocities, time intervals, and reversals were analyzed. Groups were compared, and independent risk factors for necrotizing enterocolitis were determined. RESULTS: The groups were similar with regard to weight, pulse pressure, use of prostaglandins or inotropes, presence of a patent ductus arteriosus, and systolic function. However, 47% of the case subjects with necrotizing enterocolitis had persistent retrograde diastolic flow in the abdominal aorta compared with 15% of the control subjects. When adjusting for multiple risk factors, persistent diastolic flow reversal remained the only factor significantly associated with necrotizing enterocolitis. CONCLUSION: Persistent diastolic flow reversal in the abdominal aortic Doppler profile is associated with an increased risk of necrotizing enterocolitis in term infants with congenital heart disease irrespective of gestational age or anatomic type of congenital heart disease. PMID- 17272624 TI - The impact of placement stability on behavioral well-being for children in foster care. AB - OBJECTIVE: The problems children have upon entering foster care can potentially explain prior research findings that frequent placement changes are associated with poor outcomes. This study sought to disentangle this cascading relationship in order to identify the independent impact of placement stability on behavioral outcomes downstream. DESIGN/METHODS: Placement stability over the first 18 months in out-of-home care for 729 children from the National Survey of Child and Adolescent Well-being was categorized as early stability (stable placement within 45 days), late stability (stable placement beyond 45 days), or unstable (never achieving stability). Propensity scores predicting placement instability based on baseline attributes were divided into risk categories and added to a logistic regression model to examine the independent association between placement stability and behavioral well-being using the Child Behavior Checklist and temperament scores from the National Longitudinal Survey of Youth. RESULTS: Half (52%) of the children achieved early stability, 19% achieved later stability, and 28% remained unstable. Early stabilizers were more likely to be young, have normal baseline behavior, have no prior history with child welfare, and have birth parents without mental health problems. After accounting for baseline attributes, stability remained an important predictor of well-being at 18 months. Unstable children were more likely to have behavior problems than children who achieved early stability across every level of risk for instability. Among low risk children, the probability of behavioral problems among early stabilizers was 22%, compared to 36% among unstable children, showing a 63% increase in behavior problems due to instability alone. CONCLUSIONS: Children in foster care experience placement instability unrelated to their baseline problems, and this instability has a significant impact on their behavioral well-being. This finding would support the development of interventions that promote placement stability as a means to improve outcomes among youth entering care. PMID- 17272625 TI - Annual summary of vital statistics: 2005. AB - The general fertility rate in 2005 was 66.7 births per 1000 women aged 15 to 44 years, the highest level since 1993. The birth rate for teen mothers (aged 15 to 19 years) declined by 2% between 2004 and 2005, falling to 40.4 births per 1000 women, the lowest ever recorded in the 65 years for which there are consistent data. The birth rates for women > or = 30 years of age rose in 2005 to levels not seen in almost 40 years. Childbearing by unmarried women also increased to historic record levels for the United States in 2005. The cesarean-delivery rate rose by 4% in 2005 to 30.2% of all births, another record high. The preterm birth rate continued to rise (to 12.7% in 2005), as did the rate for low birth weight births (8.2%). The infant mortality rate was 6.79 infant deaths per 1000 live births in 2004, not statistically different from the rate in 2003. Pronounced differences in infant mortality rates by race and Hispanic origin continue, with non-Hispanic black newborns more than twice as likely as non-Hispanic white and Hispanic infants to die within 1 year of birth. The expectation of life at birth reached a record high in 2004 of 77.8 years for all gender and race groups combined. Death rates in the United States continued to decline, with death rates decreasing for 9 of the 15 leading causes. The crude death rate for children aged 1 to 19 years did not decrease significantly between 2003 and 2004. Of the 10 leading causes of death for 2004 in this age group, only the rates for influenza and pneumonia showed a significant decrease. The death rates increased for intentional self-harm (suicide), whereas rates for other causes did not change significantly for children. A large proportion of childhood deaths continue to occur as a result of preventable injuries. PMID- 17272626 TI - Nonphysician clinicians in the neonatal intensive care unit: meeting the needs of our smallest patients. AB - Regional variations in the distribution of neonatal physicians and dependence on housestaff with restricted work hours have created workforce shortages in many NICUs. Although neonatal nurse practitioners assist in the delivery of high quality care, availability of these providers may be inadequate in certain regions. Physician assistants represent a historically underutilized resource to resolve neonatology's workforce issues. We have developed a postgraduate training program for physician assistants in neonatology that we hope will improve local and regional workforce shortages. In this article we discuss the history of neonatal nurse practitioners and physician assistants in newborn care and outline the program that we developed. We further discuss some of the barriers we had to overcome in developing this program. Our program can serve as a model for other neonatology programs to adequately prepare physician assistants for a career in the NICU. PMID- 17272627 TI - The use of statins in pediatrics: knowledge base, limitations, and future directions. AB - The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, effectively reduce coronary morbidity and mortality in high-risk adults. They are also some of the most widely prescribed medications in the United States. Their use in pediatrics, however, remains circumscribed. In this article we review the cholesterol hypothesis and focus on the knowledge base of the use of statins in adults and children. We pay particular attention to the known effects of statins in primary and secondary prevention of cardiovascular events. The toxicities of statins and their limitations in pediatrics are then considered. The use of statins in conjunction with noninvasive modalities of assessing atherosclerotic burden are also reviewed. Finally, we suggest methods to advance the use of statins in childhood that introduce their potential benefits to those individuals at highest risk for future events. PMID- 17272628 TI - Time for pressure tactics. PMID- 17272629 TI - Percutaneous device closure of atrial septal defect in a premature infant with rapid improvement in pulmonary status. AB - Atrial septal defects are a common congenital heart defect and may complicate the course of a premature infant by imposing volume overload to the lungs. Surgical closure requires cardiopulmonary bypass and, frequently, a midline sternotomy. Recently, percutaneous transcatheter devices were approved for atrial septal defect closure but have been limited to use in larger children. Here we present the first known report of a transcatheter device closure of an atrial septal defect in a premature infant, which resulted in rapid improvement of the patient's respiratory status. PMID- 17272630 TI - Noninitiation or withdrawal of intensive care for high-risk newborns. AB - Advances in medical technology have led to dilemmas in initiation and withdrawal of intensive care of newborn infants with a very poor prognosis. Physicians and parents together must make difficult decisions guided by their understanding of the child's best interest. The foundation for these decisions consists of several key elements: (1) direct and open communication between the health care team and the parents of the child with regard to the medical status, prognosis, and treatment options; (2) inclusion of the parents as active participants in the decision process; (3) continuation of comfort care even when intensive care is not being provided; and (4) treatment decisions that are guided primarily by the best interest of the child. PMID- 17272632 TI - Neonatal screening: old dogma or sound principle? PMID- 17272633 TI - Preventing pediatric sudden cardiac death. PMID- 17272634 TI - Stimulants and sudden death: what is the real risk? PMID- 17272635 TI - Long-term health outcomes of extremely premature infants. PMID- 17272636 TI - Residency faculty as hospitalists. PMID- 17272637 TI - Lack of association between video game exposure and school performance. PMID- 17272638 TI - False-positive results in expanded newborn screening. PMID- 17272639 TI - Could hearing loss be related to delay in administration of other antibiotics rather than early use of vancomycin? PMID- 17272640 TI - Long-term risk of atypical fungal infection after near-drowning episodes. PMID- 17272641 TI - Acetaminophen protein adducts in children with acute liver failure of indeterminate cause. PMID- 17272642 TI - Good news for patients and medical staff: a new system to assist with intravenous procedures. PMID- 17272643 TI - Ketorolac and renal compromise in neonates. PMID- 17272644 TI - Hypothermia: a neuroprotective therapy for neonatal hypoxic-ischemic encephalopathy. PMID- 17272645 TI - Childhood obesity: a passive route to physical activity. PMID- 17272646 TI - Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells. AB - E-cadherin (E-cad) is a transmembrane adhesion glycoprotein, the expression of which is often reduced in invasive or metastatic tumors. To assess E-cad's distribution among different types of cancer cells, we used bisulfite-sequencing for detailed, base-by-base measurement of CpG methylation in E-cad's promoter region in the NCI-60 cell lines. The mean methylation levels of the cell lines were distributed bimodally, with values pushed toward either the high or low end of the methylation scale. The 38 epithelial cell lines showed substantially lower (28%) mean methylation levels compared with the nonepithelial cell lines (58%). The CpG site at -143 with respect to the transcriptional start was commonly methylated at intermediate levels, even in cell lines with low overall DNA methylation. We also profiled the NCI-60 cell lines using Affymetrix U133 microarrays and found E-cad expression to be correlated with E-cad methylation at highly statistically significant levels. Above a threshold of approximately 20% to 30% mean methylation, the expression of E-cad was effectively silenced. Overall, this study provides a type of detailed analysis of methylation that can also be applied to other cancer-related genes. As has been shown in recent years, DNA methylation status can serve as a biomarker for use in choosing therapy. PMID- 17272647 TI - Multiple sequence alignment: in pursuit of homologous DNA positions. AB - DNA sequence alignment is a prerequisite to virtually all comparative genomic analyses, including the identification of conserved sequence motifs, estimation of evolutionary divergence between sequences, and inference of historical relationships among genes and species. While it is mere common sense that inaccuracies in multiple sequence alignments can have detrimental effects on downstream analyses, it is important to know the extent to which the inferences drawn from these alignments are robust to errors and biases inherent in all sequence alignments. A survey of investigations into strengths and weaknesses of sequence alignments reveals, as expected, that alignment quality is generally poor for two distantly related sequences and can often be improved by adding additional sequences as stepping stones between distantly related species. Errors in sequence alignment are also found to have a significant negative effect on subsequent inference of sequence divergence, phylogenetic trees, and conserved motifs. However, our understanding of alignment biases remains rudimentary, and sequence alignment procedures continue to be used somewhat like benign formatting operations to make sequences equal in length. Because of the central role these alignments now play in our endeavors to establish the tree of life and to identify important parts of genomes through evolutionary functional genomics, we see a need for increased community effort to investigate influences of alignment bias on the accuracy of large-scale comparative genomics. PMID- 17272648 TI - Severe reflux disease is associated with an enlarged unbuffered proximal gastric acid pocket. AB - BACKGROUND: An unbuffered pocket of highly acidic juice is observed at the gastric cardia after a meal in healthy subjects. AIMS: To compare the postprandial acid pocket in healthy subjects and patients with severe reflux disease and define its position relative to anatomical and manometric landmarks. METHODS: 12 healthy subjects and 16 patients with severe reflux disease were studied. While fasted, a station pull-through was performed using a combined dual pH and manometry catheter. Position was confirmed by radiological visualisation of endoscopically placed radio-opaque clips. The pull-through study was repeated 15 min after a standardised fatty meal. Barium meal examination was performed before and following the meal. RESULTS: A region of unbuffered acid (pH t variants. Only RXRgamma Ser14 was more frequent in FCHL (15%, P<0.05) than in other primary hyperlipidemia (4%) and in controls (5%). Among patients suspected of coronary disease, we identified 9 RXRgamma Ser14 carriers, who showed increased triglycerides (1.62+/-0.82 versus 1.91+/-0.42 [mean+/-SD] mmol/L, P<0.05), decreased HDL-cholesterol (1.32+/-0.41 versus 1.04+/-0.26, P<0.05), and decreased post-heparin plasma lipoprotein lipase protein levels (222+/-85 versus 149+/-38 ng/mL, P<0.01). In vitro, RXRgamma Ser14 showed significantly stronger repression of the lipoprotein lipase promoter than RXRgamma Gly14. CONCLUSION: These findings suggest that RXRgamma contributes to the genetic background of FCHL. PMID- 17272749 TI - Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis. AB - OBJECTIVE: Naturally occurring CD4+ CD25+ regulatory T cells (Tregs) exert suppressive effects on effector CD4 cells and downregulate experimental autoimmune disorders. We investigated the importance and potential role of Tregs in murine atherogenesis. METHODS AND RESULTS: Tregs were investigated comparatively between aged and young apolipoprotein E-knockout (ApoE-KO) mice and age-matched C57BL/6 littermates. The effect of oxidized LDL (oxLDL) was tested on the functional suppressive properties of Tregs from ApoE-KO and C57BL/6 mice. Tregs, CD4+ CD25- cells, and saline were infused into ApoE-KO mice to study their effects on atherogenesis. Treg numbers were reduced in atherosclerotic compared with nonatherosclerotic ApoE-KO mice. The functional suppressive properties of Tregs from ApoE-KO mice were compromised in comparison with those from their C57BL/6 littermates. Thus, oxLDL attenuated the suppressive properties of Tregs from C57BL/6 mice and more so in ApoE-KO mice. Transfer of Tregs from age-matched ApoE-KO mice resulted in significant attenuation of atherosclerosis compared with that after delivery of CD4+ CD25+/- T cells or phosphate-buffered saline. CONCLUSIONS: CD4+ CD25+ Tregs may play a protective role in the progression of atherosclerosis and could be considered a therapeutic tool if results from human studies can solidify observations in murine models. PMID- 17272750 TI - Factor IXa inhibitors as novel anticoagulants. AB - Currently available anticoagulants are limited by modest therapeutic benefits, narrow clinical applications, increased bleeding risk, and drug-induced thrombophilia. Because factor IX plays a pivotal role in tissue factor (TF) mediated thrombin generation, it may represent a promising target for drug development. Several methods of attenuating factor IX activity, including monoclonal antibodies, synthetic active site-blocked competitive inhibitors, oral inhibitors, and RNA aptamers, have undergone investigation. This review summarizes present knowledge of factor IX inhibitors with emphasis on biology, pharmacology, preclinical data, and early-phase clinical experience in humans. PMID- 17272751 TI - CD44 regulates vascular gene expression in a proatherogenic environment. AB - OBJECTIVE: To identify early changes in vascular gene expression mediated by CD44 that promote atherosclerotic disease in apolipoprotein E (apoE)-deficient (apoE-/ ) mice. METHODS AND RESULTS: We demonstrate that CD44 is upregulated and functionally activated in aortic arch in the atherogenic environment of apoE-/- mice relative to wild-type (C57BL/6) controls. Moreover, CD44 activation even in apoE-/- mice is selective to lesion-prone regions because neither the thoracic aorta from apoE-/- mice nor the aortic arch of C57BL/6 mice exhibited upregulation of CD44 compared with thoracic aorta of CD57BL/6 mice. Consistent with these observations, gene expression profiling using cDNA microarrays and quantitative polymerase chain reaction revealed that approximately 155 of 19,200 genes analyzed were differentially regulated in the aortic arch, but not in the thoracic aorta, in apoE-/- CD44-/- mice compared with apoE-/- CD44+/+ mice. However, these genes were not regulated by CD44 in the context of a C57BL/6 background, illustrating the selective impact of CD44 on gene expression in a proatherogenic environment. The patterns of differential gene expression implicate CD44 in focal adhesion formation, extracellular matrix deposition, and angiogenesis, processes critical to atherosclerosis. CONCLUSIONS: CD44 is an early mediator of atherogenesis by virtue of its ability to regulate vascular gene expression in response to a proatherogenic environment. PMID- 17272752 TI - Phospholipid transfer protein augments apoptosis in THP-1-derived macrophages induced by lipolyzed hypertriglyceridemic plasma. AB - OBJECTIVE: Lipolysis of triglyceride-rich lipoproteins (TGRLPs) generates phospholipid-rich surface remnants and induces cytotoxic effects in adjacent vascular cells. We hypothesized that by integrating surface remnants into HDL, phospholipid transfer protein (PLTP) alleviates cytotoxicity. METHODS AND RESULTS: To test this hypothesis and gain insight into cytotoxicity during the postprandial phase in vivo, we injected normo-TG and hyper-TG human volunteers after a standardized fat meal (postprandial sample) with heparin, thereby stimulating lipolysis (postprandial heparinized sample). Incubation of (primary) human macrophages and primary human endothelial cells with postprandial heparinized hyper-TG plasma induced pronounced cytotoxic effects that were dose dependent on the TG content of the sample. No such effects were seen with normo TG and postprandial hyper-TG plasma. In vitro lipolysis of VLDL and chylomicrons indicated that both lipoprotein fractions can cause cytotoxicity. Interestingly, in experiments with THP-1-derived macrophages stably transfected with PLTP, PLTP substantially augmented both net phospholipid uptake and apoptotic cell death due to postprandial heparinized hyper-TG plasma. We observed that activation of caspase-3/7, poly-ADP-ribose polymerase, and enhanced bioactivity of acid sphingomyelinase may all contribute to this augmented apoptosis. CONCLUSIONS: Our data show that lipolysis of TGRLPs and their remodelling by PLTP interact to disturb cellular phospholipid flux and intracellular signaling processes, ultimately leading to apoptosis in human macrophages and endothelial cells. PMID- 17272753 TI - Plasmin induces endothelium-dependent nitric oxide-mediated relaxation in the porcine coronary artery. AB - OBJECTIVE: Plasmin is a key enzyme in fibrinolysis. We attempted to determine the possible role of plasmin in the regulation of vascular tone, while also investigating the mechanism of plasmin-induced vasorelaxation. METHODS AND RESULTS: In porcine coronary artery, plasmin induced an endothelium-dependent relaxation. This relaxing effect was mostly abolished by a proteinase inhibitor, a plasmin inhibitor, or a nitric oxide (NO) synthase inhibitor. The preceding stimulation with plasmin significantly inhibited the subsequent relaxation induced by thrombin but not that induced by proteinase-activated receptor-1 activating peptide. The relaxation induced by trypsin and substance P remained unaffected by the preceding plasmin stimulation. The pretreatment with plasmin, thrombin, or trypsin significantly attenuated the plasmin-induced relaxation. In porcine coronary artery endothelial cells (PCAECs) and human umbilical vein endothelial cells (HUVECs), plasmin induced a transient elevation in the cytosolic Ca2+ concentrations ([Ca2+]i). The preceding stimulation with plasmin inhibited the subsequent [Ca2+]i elevation induced by thrombin but not that induced by trypsin. In PCAECs, plasmin concentration-dependently induced NO production. CONCLUSIONS: The present study demonstrated, for the first time, that plasmin induced an endothelium-dependent NO-mediated relaxation in the porcine coronary artery, while also showing plasmin to specifically inactivate the thrombin receptor. PMID- 17272754 TI - Platelet adhesion receptors and their ligands in mouse models of thrombosis. AB - Platelet adhesion and aggregation at sites of vascular injury are two key events in hemostasis and thrombosis. Because of exciting advances in genetic engineering, the mouse has become an important and frequently used model to unravel the molecular mechanisms underlying the multistep process leading to the formation of a stable platelet plug. In gene-targeted mice, the crucial importance of platelet adhesion receptors such as glycoprotein Ib alpha or the alphaIIb beta3 integrin has been confirmed and further clarified. Their absence leads to highly impaired thrombus formation, independent of the model used to induce vascular injury. In contrast, the relative contribution of other receptors, such as glycoprotein VI, or of various platelet ligands may be regulated by the severity of injury, the type of vessel injured, and the signaling pathways that are generated. Murine models have also helped improve understanding of the second wave of events that leads to stabilization of the platelet aggregate. Despite the current limitations due to lack of standardization and the virtual absence of thrombosis models in diseased vessels, there is no doubt that the mouse will play a key role in the discovery and characterization of the next generation of antithrombotic agents. This review focuses on key findings about the molecular mechanisms supporting hemostasis and thrombosis that have been obtained with genetically engineered mouse models deficient in various platelet adhesion receptors and ligands. Combination of these models with sophisticated methods allowing direct visualization of platelet vessel wall interactions after injury greatly contributed to recent advances in the field. PMID- 17272755 TI - Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice. AB - BACKGROUND: We hypothesized that atherosclerosis inhibits NO-mediated endothelium dependent dilation of coronary arterioles through interaction of ox-LDL with its receptor, LOX-1, through the production of O2y- in endothelial cells. METHODS AND RESULTS: We assessed the role of ox-LDL in endothelial dysfunction in a murine model of atherosclerosis (ApoE KO mice). Coronary arterioles from WT control and ApoE KO mice were isolated and pressurized without flow. Although dilation of vessels to endothelium-independent vasodilator SNP was not altered between ApoE KO and WT mice, dilation to the endothelium-dependent agonist, ACh was reduced in ApoE KO versus WT mice. Impaired vasodilation to ACh in ApoE KO mice is partially restored by NAD(P)H oxidase inhibitor, apocynin or DPI. Messenger RNA expression for NAD(P)H oxidases was higher in ApoE KO mice than that in WT and anti-LOX-1 treated ApoE KO mice. Anti-LOX-1, given in vivo, restored NO-mediated coronary arteriolar dilation in ApoE KO mice, but did not affect the endothelium-dependent vasodilation in controls. CONCLUSIONS: These results suggest that ox-LDL impairs endothelium-dependent NO-mediated dilation of coronary arterioles by activation of a signaling cascade involving LOX-1 and NAD(P)H oxidase expression. PMID- 17272756 TI - Cholesteryl ester transfer protein (CETP) expression protects against diet induced atherosclerosis in SR-BI deficient mice. AB - OBJECTIVE: To determine whether expression of the human CETP transgene protects against diet-induced atherosclerosis in SR-BI deficient mice. METHODS AND RESULTS: SR-BI deficient (-/-) mice were crossed with CETP transgenic (CETPtg) mice to produce a colony of SR-BI(-/-) x CETPtg mice in a C57Bl/6 background. Age and sex matched groups of genetically modified and wild-type C57Bl/6 mice were fed a high fat, high cholesterol diet for 22 weeks. In both wild-type and SR-BI( /-) mice, expression of the CETP transgene reduced the cholesterol content and increased the density of lipoprotein particles in the HDL density range. In SR BI(-/-) x CETPtg mice, CETP activity inversely correlated with total plasma cholesterol levels and shifted the buoyant HDL typical of SR-BI deficiency toward a more normal density HDL particle. Atherosclerosis at the level of the aortic arch was evident in both male and female SR-BI deficient mice but occurred to a greater extent in the females. Expression of CETP markedly attenuated the development of atherosclerosis in SR-BI deficient mice fed an atherogenic diet (P<0.003). CONCLUSIONS: Expression of the human CETP transgene protects SR-BI deficient mice from atherosclerosis, consistent with a role for CETP in remodeling HDL and providing an alternative pathway for the selective uptake of HDL-CE by the liver. PMID- 17272757 TI - Downregulation of bone morphogenetic protein 4 expression in coronary arterial endothelial cells: role of shear stress and the cAMP/protein kinase A pathway. AB - OBJECTIVE: Bone morphogenetic protein 4 (BMP-4) is a transforming growth factor beta family member cytokine that exerts proinflammatory effects on the endothelium and is likely to play a role in atherogenesis. Recent studies suggested that atheroprotective levels of shear stress control endothelial BMP-4 expression; however, the underlying mechanisms remained unknown. METHODS AND RESULTS: We found that shear stress downregulated BMP-4 expression in human and rat coronary arterial endothelial cells (CAECs) as well as in cultured mesenteric arterioles, although it had no effect on the expression of BMP-2, a related cytokine. In human coronary arterial endothelial cells, 8-bromo-cAMP, the adenylate cyclase activator forskolin, or a cAMP-dependent protein kinase (PKA) activator effectively decreased BMP-4 expression, mimicking the effects of shear stress. Indeed, shear stress induced the nuclear translocation of PKA-c, and inhibition of PKA attenuated the effects of shear stress and forskolin on BMP-4 expression. RNA decay assay and BMP-4 promoter-driven luciferase reporter gene assay showed that cAMP regulates BMP-4 expression at the transcriptional level. CONCLUSIONS: Laminar shear stress and the cAMP/PKA pathway are important negative regulators of BMP-4 expression in the vascular endothelium. Because BMP-4 elicits endothelial activation and dysfunction, hypertension, and vascular calcification, inhibition of BMP-4 expression by shear stress and the cAMP/PKA pathway is likely to exert antiatherogenic and vasculoprotective effects. PMID- 17272758 TI - The metabolic syndrome and the carotid artery structure in noninstitutionalized elderly subjects: the three-city study. AB - BACKGROUND AND PURPOSE: In contrast to the young adult population, limited data are presently available regarding the epidemiology of the metabolic syndrome (MetS) and its relationship with cardiovascular disease risk in the elderly. We have investigated the frequency of the MetS and its association with the carotid artery structure in an elderly free-living population. METHODS: The study population consists of 5585 French noninstitutionalized elderly men and women aged 65 to 85 years, free of diabetes, who participated in the multicenter Three City Study and who underwent ultrasound examination of the carotid arteries at baseline examination between March 1999 and March 2001. The MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: The MetS was present in 12.1% of the study participants, with slightly higher rates in men. Subjects with the MetS had higher frequency of carotid plaques (odds ratio, 1.30; 95% CI, 1.09 to 1.55), higher intima-media thickness of the common carotid artery (odds ratio, 1.81; 95% CI, 1.37 to 2.41), and higher lumen diameter (odds ratio, 2.17; 95% CI, 1.61 to 2.94) (upper quintiles) after adjustment for other cardiovascular risk factors. This association was observed in both genders and in subjects without prevalent cardiovascular disease. Elevated blood pressure as defined in the MetS was the main determinant of the relations between the MetS and the carotid parameters, especially the lumen diameter. CONCLUSIONS: The present data suggest that noninstitutionalized elderly subjects with the MetS have altered structure of the carotid arteries. PMID- 17272760 TI - Lecithinized superoxide dismutase improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats. AB - BACKGROUND AND PURPOSE: Recent studies have shown the antiapoptotic neuroprotective effects of lecithinized superoxide dismutase (PC-SOD) in different forms of brain injury. We tested the effects of PC-SOD in focal cerebral ischemia in the rat middle cerebral artery occlusion model (MCAO). METHODS: Adult male Sprague-Dawley rats were treated with PC-SOD (0.3, 1.0, and 3.0 mg/kg) administered intravenously after 90 minutes of occlusion (beginning of reperfusion). Physiological parameters, neurological score, and infarct volume were assessed at 24 and 72 hours in 3 groups of animals: sham-operated (n=18), MCAO treated with vehicle (n=26), and MCAO treated with PC-SOD (n=37). Oxidative stress was evaluated by malondialdehyde assay, and the apoptotic mechanisms were studied by Western blotting. RESULTS: PC-SOD treatment significantly reduced infarct volume and improved neurological scores at different time points compared with the vehicle-treated group. PC-SOD treatment decreased malondialdehyde levels, cytochrome c, and cleaved caspase 3 expression and increased mitochondrial Bcl-2 expression. CONCLUSIONS: Inhibition of oxidative stress with PC-SOD treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by antiapoptotic mechanisms. PMID- 17272759 TI - Neuroprotective role of transgenic PAF-acetylhydrolase II in mouse models of focal cerebral ischemia. AB - BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults. METHODS: Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively. RESULTS: Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (P<0.05) lower in transgenic mice (1.30+/-0.72, 1.12+/-0.04, and 14.0+/-7.7%, respectively) than in wild-type mice (2.56+/-0.93, 1.23+/-0.12, and 31.9+/-9.7%, respectively). Percentages of apoptotic cells were also significantly (P<0.001) lower in transgenic mice (cortex, 5.2+/-3.3%; hippocampus, 3.4+/-7.0%) than in wild-type mice (cortex, 41.1+/-16.9%; hippocampus, 58.9+/-15.3%). CONCLUSIONS: These results indicate that PAF-AH II exerts strong neuroprotective effects against ischemic injury and suggest a possibility for clinical use of this enzyme in cerebral ischemia. PMID- 17272761 TI - Lacunar infarcts are the main correlate with cognitive dysfunction in CADASIL. AB - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke and cognitive decline. Previous studies have shown an association between white matter hyperintensities on brain MRI and cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. In the general population the presence of lacunar infarcts and microbleeds is also associated with cognitive dysfunction. The objective of this study was to determine to what extent lacunar infarcts and microbleeds on MRI contribute to cognitive decline in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. METHODS: NOTCH3 mutation analysis was performed in 62 symptomatic and asymptomatic members of 15 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy families. Neuropsychological tests were performed on the same day as the MRI examination. MRI was semi-quantitatively scored for white matter hyperintensities, infarct lesion load, and microbleeds. Regression analysis was performed to test the association between MRI abnormalities and neuropsychological test results. RESULTS: Forty individuals had a NOTCH3 mutation and 22 did not. Severity of cognitive dysfunction in mutation carriers was independently associated with MRI infarct lesion load (P<0.05). In contrast, WMH lesion load and microbleeds were not associated with cognitive dysfunction after correcting for age. CONCLUSIONS: Lacunar infarct lesion load is the most important MRI parameter associated with cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. PMID- 17272762 TI - Aging-associated vascular phenotype in mutant mice with low levels of BubR1. AB - BACKGROUND AND PURPOSE: Aging is a major risk for stroke and a highly complex biological process believed to involve multiple mechanisms. Mutant mice that express low levels of the spindle assembly checkpoint protein BubR1 are known to develop several aging-associated phenotypes at a very young age, including cataracts, lordokyphosis, loss of subcutaneous fat, and impaired wound healing. However, whether BubR1 acts to prevent vascular aging has not yet been established. The present study was designed to investigate the vascular phenotype of mutant mice with low levels of BubR1. METHODS: Morphological, functional, and biochemical analyses were performed on aortas and carotid arteries of 3- to 5 month-old BubR1 mutant mice and wild-type littermates. RESULTS: Arterial wall thickness and inner diameter were significantly reduced in BubR1 mutant mice. Arterial walls of BubR1 mutant mice had low numbers of medial smooth muscle cells. Masson trichrome staining showed profound fibrosis in arterial walls of BubR1 mutant. In agreement with these morphological changes, functional analysis of pressurized isolated carotid arteries of BubR1 mutant mice demonstrated reduced elastic properties. Endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to the nitric oxide donor DEA-NONOate were significantly reduced in carotid arteries of BubR1 mutant mice. Furthermore, enzymatic activity of nitric oxide synthase and levels of cyclic GMP were significantly reduced in aortas of mutant mice, but production of superoxide anions was significantly increased. CONCLUSIONS: These findings demonstrate that BubR1 insufficiency in mice results in phenotypic changes reminiscent of vascular aging in humans and suggest a role for BubR1 in suppressing the vascular aging process. PMID- 17272763 TI - Therapeutic application of 20-kHz transcranial ultrasound in an embolic middle cerebral artery occlusion model in rats: safety concerns. AB - BACKGROUND AND PURPOSE: Therapeutic application of diagnostic ultrasound has been shown to improve recanalization rates in patients with acute cerebral vessel occlusion. There is experimental evidence that low-frequency ultrasound may be superior. This study was designed to evaluate the therapeutic efficacy and safety of low-frequency ultrasound in an embolic middle cerebral artery occlusion model in rats. A parameter setting was used that had not previously shown any side effects and interactions with healthy rat brain tissue. METHODS: Male Wistar rats were submitted to middle cerebral artery clot embolism and transcranial treatment with 20-kHz continuous-wave ultrasound (0.2 W/cm(2)), either alone or in combination with recombinant tissue-type plasminogen activator. Control groups received no treatment or recombinant tissue-type plasminogen activator alone. Outcome assessment consisted of determination of infarct volume and neurological evaluation. RESULTS: Eleven animals treated with ultrasound died during the follow-up period of 7 days, compared with 2 animals in the control groups (P=0.028). In 3 animals, subarachnoid hemorrhage was detected (1 in the control group). The other animals that died displayed secondary worsening after an initial period of normal vigilance. Histological examination revealed massive edema formation. In surviving animals, no benefit of treatment could be demonstrated. CONCLUSIONS: In this study, 20-kHz continuous-wave ultrasound caused death in a significant number of animals. Ultrasound at 20 kHz does not seem to be suitable for transcranial therapeutic cerebral application. The data underline the necessity to obtain further animal data to establish the safety limits of frequency and power output. PMID- 17272764 TI - Continuous monitoring of cerebrovascular autoregulation after subarachnoid hemorrhage by brain tissue oxygen pressure reactivity and its relation to delayed cerebral infarction. AB - BACKGROUND AND PURPOSE: Disturbances of cerebrovascular autoregulation are thought to be involved in delayed cerebral ischemia and infarction after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that the continuous monitoring of brain tissue oxygen (PtiO(2)) pressure reactivity enables the detection of impaired autoregulation after SAH and that impaired autoregulation is associated with delayed infarction. METHODS: In 67 patients after severe SAH, continuous monitoring of cerebral perfusion pressure (CPP) and PtiO(2) was performed for an average of 7.4 days. For assessment of autoregulation, the index of PtiO(2) pressure reactivity (ORx) was calculated as a moving correlation coefficient between values of CPP and PtiO(2). Higher ORx values indicate disturbed autoregulation, whereas lower ORx values signify intact autoregulation. RESULTS: Twenty patients developed delayed cerebral infarction, and 47 did not. Mean ORx was significantly higher in the infarction group compared with the noninfarction group (0.43+/-0.09 vs 0.23+/-0.14, respectively; P<0.0001). In a day-by-day analysis, ORx did not differ between groups from days 1 to 4 after SAH but was significantly higher from day 5 onward in the infarction group, indicating a deficit of autoregulatory capacity. In a logistic-regression model, ORx values from days 5 and 6 after SAH carried predictive value for the occurrence of delayed infarction but before this event ultimately occurred (P=0.003). CONCLUSIONS: ORx indicates impaired autoregulation in patients who develop delayed infarction after SAH. Furthermore, this index may distinguish between patients who finally develop delayed infarction and those who do not. PMID- 17272765 TI - Decompressive hemicraniectomy for the treatment of intractable intracranial hypertension after aneurysmal subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Decompressive hemicraniectomy and duroplasty (DHCD) can improve survival in patients with severe cerebral edema. We present our clinical experience with DHCD for the treatment of refractory elevated intracranial pressure (ICP) in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: DHCD was performed in 16 patients (11 female; median age, 49.5 years) with aSAH (11 Hunt-Hess grade 4 to 5) for sustained ICP >250 mm H(2)O refractory to maximal medical treatment and cerebrospinal fluid drainage at a median of 2 days from admission. Half of the patients were treated with endovascular coiling and the other half with surgical clipping. RESULTS: DHCD (mean flap size, 8536 mm(2)) reduced ICP from 350+/-157 to 147+/-124 mm H(2)O. Eleven patients survived (69%), and at latest follow-up (median, 450 days), 7 (64%) had a modified Rankin score of 0 to 3 and 4 (36%) a score of 4 to 5. Peak herniated brain volume was inversely associated with good outcome (P<0.005). Early craniectomy performed within 48 hours after the aSAH was associated with better outcome: 6 of 8 patients had good outcomes (75%) compared with 1 of 8 patients in whom late decompression was performed (P<0.01). Midline shift, Hunt-Hess grade, presence of hemorrhage, hematoma volume, craniectomy area, peak ICP, and relative ICP reduction were not associated with outcome in this patient population. CONCLUSIONS: DHCD is a useful adjunct modality for management of refractory intracranial hypertension in patients with high-grade aSAH, even in the absence of large intraparenchymal hemorrhage. In our series, long-term outcome was better in patients who underwent early intervention. PMID- 17272767 TI - Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. AB - BACKGROUND AND PURPOSE: The modified Rankin scale (mRS), a clinician-reported measure of global disability, is widely applied for evaluating stroke patient outcomes and as an end point in randomized clinical trials. Extensive evidence on the validity of the mRS exists across a large but fragmented literature. As new treatments for acute ischemic stroke are submitted for agency approval, an appreciation of the mRS's attributes, specifically its relationship to other stroke evaluation scales, would be valuable for decision-makers to properly assess the impact of a new drug on treatment paradigms. The purpose of this report is to assemble and systematically assess the properties of the mRS to provide decision-makers with pertinent evaluative information. METHODS: A Medline search was conducted to identify reports in the peer-reviewed medical literature (1957-2006) that provide information on the structure, validation, scoring, and psychometric properties of the mRS and its use in clinical trials. The selection of articles was based on defined criteria that included relevance, study design and use of appropriate statistical methods. RESULTS: Of 224 articles identified by the literature search, 50 were selected for detailed assessment. Inter-rater reliability with the mRS is moderate and improves with structured interviews (kappa 0.56 versus 0.78); strong test-re-test reliability (kappa=0.81 to 0.95) has been reported. Numerous studies demonstrate the construct validity of the mRS by its relationships to physiological indicators such as stroke type, lesion size, perfusion and neurological impairment. Convergent validity between the mRS and other disability scales is well documented. Patient comorbidities and socioeconomic factors should be considered in properly applying and interpreting the mRS. Recent analyses suggest that randomized clinical trials of acute stroke treatments may require a smaller sample size if the mRS is used as a primary end point rather than the Barthel Index. CONCLUSIONS: Multiple types of evidence attest to the validity and reliability of the mRS. The reported data support the view that the mRS is a valuable instrument for assessing the impact of new stroke treatments. PMID- 17272769 TI - Intensive statin therapy after stroke or transient ischemic attack: a SPARCLing success? PMID- 17272770 TI - Low-grade inflammation is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives: the Jichi Medical School ABPM Study, wave 1. AB - BACKGROUND AND PURPOSE: High-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is associated with atherosclerosis, hypertensive target organ damage, and cardiovascular events. In the general Japanese population, the level of hsCRP is reported to be lower than that in Western countries, and the relationships among hsCRP, silent cerebral infarcts (SCIs), and clinical stroke events in older Japanese hypertensives remain unclear. METHODS: We conducted brain MRI and measured hsCRP at baseline in 514 older Japanese hypertensives (clinic blood pressure > or =140/90 mm Hg, age > or =50 years old) who were enrolled in the Jichi Medical School ABPM Study, wave 1. They were followed up for an average of 41 months (range: 1 to 68 months, 1751 person-years) and the incidence of subsequent clinical stroke events was evaluated. RESULTS: The subjects with SCIs at baseline (n=257) had a higher hsCRP level than those without SCIs (geometric mean hsCRP [SD range]; 0.19 [0.18 to 0.21] versus 0.14 [0.13 to 0.16] mg/L, P=0.007) after adjustment for confounding factors, and the OR for the presence of SCIs was increased with the quartile of hsCRP levels. In Cox regression analysis, the patients with above median hsCRP level (> or =0.21 mg/L) (hazard ratio [HR]: 2.50, 95% CI: 1.24 to 5.00, P=0.01) and those with SCIs (HR: 4.60, 95% CI: 1.91 to 11.03, P=0.001) at baseline had independently higher risks for clinical stroke events after adjustment for age, smoking status, antihypertensive medication use, and 24-hour systolic blood pressure level. Compared with the patients with below median hsCRP level without SCIs, those with above median hsCRP level and SCIs at baseline had a higher risk for clinical stroke events (HR: 7.32, 95% CI: 2.17 to 24.76, P=0.001), although those with below median hsCRP level and SCIs (HR: 2.46, 95% CI: 0.64 to 9.47, P=0.19) and those with above median hsCRP level without SCIs (HR: 1.11, 95% CI: 0.22 to 5.55, P=0.90) did not have significant risks. CONCLUSIONS: High-sensitivity C-reactive protein is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives, indicating that the risk for clinical stroke events increases with preexisting hypertensive target organ damage in the brain and additionally with ongoing low-grade inflammation. PMID- 17272771 TI - Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling. AB - BACKGROUND AND PURPOSE: Exposure of animals for a few hours to moderate hypoxia confers relative protection against subsequent ischemic brain damage. This phenomenon, known as hypoxic preconditioning, depends on new RNA and protein synthesis, but its molecular mechanisms are poorly understood. Increased expression of IL-6 is evident, particularly in the lungs of animals subjected to hypoxic preconditioning. Stanniocalcin-1 (STC-1) is a 56-kDa homodimeric glycoprotein originally discovered in bony fish, where it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. We originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 guards neurons against hypercalcemic and hypoxic damage. METHODS: We treated neural Paju cells with IL-6 and measured the induction of STC-1 mRNA. In addition, we quantified the effect of hypoxic preconditioning on Stc-1 mRNA levels in brains of wild-type and IL-6 deficient mice. Furthermore, we monitored the Stc-1 response in brains of wild-type and transgenic mice, overexpressing IL 6 in the astroglia, before and after induced brain injury. RESULTS: Hypoxic preconditioning induced an upregulated expression of Stc-1 in brains of wild-type but not of IL-6-deficient mice. Induced brain injury elicited a stronger STC-1 response in brains of transgenic mice, with targeted astroglial IL-6 expression, than in brains of wild-type mice. Moreover, IL-6 induced STC-1 expression via MAPK signaling in neural Paju cells. CONCLUSIONS: These findings indicate that IL 6-mediated expression of STC-1 is one molecular mechanism of hypoxic preconditioning-induced tolerance to brain ischemia. PMID- 17272772 TI - The impact of recanalization on ischemic stroke outcome: a meta-analysis. AB - BACKGROUND AND PURPOSE: For a biomarker to serve as an auxiliary or surrogate outcome measure, it must be tightly correlated with and causally related to functional clinical outcome. Vessel recanalization is a potential surrogate outcome marker for functional outcome in trials of thrombolytic and mechanical recanalization therapies in acute stroke, but the correlation of recanalization and clinical outcome has not been previously systematically reviewed. METHODS: Through Medline search, we identified and abstracted recanalization and outcome data from all articles published between 1985 and 2002 that assessed vessel recanalization, either spontaneous or therapeutically induced, in acute ischemic stroke. RESULTS: Fifty-three studies encompassing 2066 patients reported recanalization rates. Recanalization rates categorized according to intervention were: spontaneous (24.1%), intravenous fibrinolytic (46.2%), intra-arterial fibrinolytic (63.2%), combined intravenous-intra-arterial (67.5%), and mechanical (83.6%). Clinical outcome data categorized by success or failure in achieving recanalization was available from 33 articles encompassing 998 patients. Good functional outcomes at 3 months were more frequent in recanalized versus nonrecanalized patients with odds ratio of 4.43 (95% CI, 3.32 to 5.91). Three month mortality was reduced in recanalized patients (odds ratio, 0.24; 95% CI, 0.16 to 0.35). Rates of symptomatic hemorrhagic transformation did not differ between the 2 groups (odds ratio, 1.11; 95% CI, 0.71 to 1.74). CONCLUSIONS: Formal meta-analysis confirms a strong correlation between recanalization and outcome in acute ischemic stroke. Recanalization is strongly associated with improved functional outcomes and reduced mortality. These findings suggest that recanalization is an appropriate biomarker of therapeutic activity in early phase trials of thrombolytic treatment in acute ischemic stroke. PMID- 17272773 TI - A prospective community-based study of stroke in Kolkata, India. AB - BACKGROUND AND PURPOSE: Information on essential stroke parameters are lacking in India. This population-based study on stroke disorder was undertaken in the city of Kolkata, India, to determine the subtypes, prevalence, incidence, and case fatality rates of stroke. METHODS: This was a longitudinal descriptive study comprising 2-stage door-to-door survey of a stratified randomly selected sample of the city population, conducted twice per year for 2 successive years from March 2003 to February 2005. RESULTS: Out of the screened population of 52,377 (27 626 men, 24 751 women), the age standardized prevalence rate of stroke to world standard population is 545.10 (95% CI, 479.86 to 617.05) per 100,000 persons. The age standardized average annual incidence rate to world standard population of first-ever-in-a-lifetime stroke is 145.30 (95% CI, 120.39 to 174.74) per 100,000 persons per year. Thirty-day case fatality rate is 41.08% (95% CI, 30.66 to 53.80). Women have higher incidence and case fatality rates. Despite divergence on socioeconomic status between the slum and nonslum dwellers, stroke parameters were not significantly different. CONCLUSIONS: The age standardized prevalence and incidence rates of stroke in this study are similar to or higher than many Western nations. The overall case fatality rate is among the highest category of stroke fatality in the world. The women have higher incidence and case fatality rates compared with men. PMID- 17272774 TI - Preconditioning suppresses inflammation in neonatal hypoxic ischemia via Akt activation. AB - BACKGROUND AND PURPOSE: Hypoxic preconditioning (PC) confers robust neuroprotection against neonatal hypoxic-ischemic brain injury (H-I), yet the underlying mechanism is poorly understood. In the adult brain, neuronal survival after ischemia is associated with the activation of the phosphatidylinositol 3 kinase (PI3-K)/Akt signaling pathway. Suppression of inflammation is a newly identified direct consequence of PI3-K/Akt signaling. We therefore investigated whether PI3-K/Akt suppresses inflammation and contributes to PC-induced neuroprotection. METHODS: Postnatal day 7 rats were exposed for 3 hours to either ambient air or 8% oxygen, which induces hypoxic PC. H-I was produced 24 hours later by unilateral carotid artery ligation followed by 2.5 hours of hypoxia. Animals were euthanized 0 to 24 hours later for detecting Akt and glycogen synthetase kinase-3beta phosphorylation (p-Akt, p-GSK-3beta), 24 hours later for assessing cytokine expression and inflammatory markers, and 7 days later for measuring brain tissue loss. In addition, LY294002 was injected intracerebroventricularly to inhibit PI3-K/Akt. RESULTS: Brains with H-I without PC showed delayed but sustained reduction in p-Akt. PC restored the levels of p Akt and the Akt substrate GSK-3beta, reduced proinflammatory markers (NF-kappaB, COX-2, CD68, myeloperoxidase, and microglial activation), and markedly ameliorated H-I-induced brain tissue loss. Inhibition of PI3-K/Akt using LY294002 attenuated PC neuroprotection and promoted the expression of NF-kappaB, COX-2, and CD68. Proteomic microarray analysis revealed that PC inhibited expression of proinflammatory cytokines induced by H-I or a dose of lipopolysaccharide that resulted in minimal tissue damage. CONCLUSIONS: Suppression of inflammatory responses may contribute to PC neuroprotection against neonatal H-I brain injury. This effect is mediated in part via upregulating PI3-K/Akt activity. PMID- 17272775 TI - Quantified corticospinal tract diffusion restriction predicts neonatal stroke outcome. AB - BACKGROUND AND PURPOSE: Neonatal arterial ischemic stroke occurs in > or =1:4000 births. Many children experience motor deficits but acute predictors of outcome are lacking. Diffusion-weighted MRI changes in descending corticospinal tracts remote from arterial ischemic stroke may represent pre-Wallerian degeneration. We verify and quantify this signal and correlate it with motor outcome. METHODS: Fourteen neonates with acute arterial ischemic stroke and > or =12 months follow up with the Pediatric Stroke Outcome Measure were included. Quantitative measurements of descending corticospinal tracts diffusion-weighted MRI signal were developed using Image J software. RESULTS: Ipsilesional descending corticospinal tract diffusion-weighted MRI signal was abnormal in 10 neonates with decreased apparent diffusion coefficients (P<0.001). Poor outcome correlated with: (1) percentage of peduncle (P=0.002); (2) length of descending corticospinal tracts P<0.001); and (3) volume of descending corticospinal tracts (P=0.002). None of: (1) any peduncle; (2) any posterior limb of the internal capsule; or (3) infarct volume correlated with outcome. All children without descending corticospinal tracts signal had normal outcome. Chronic Wallerian degeneration was seen in all children with hemiparesis. Software-assisted analysis was superior to visual inspection with excellent reliability (intra class correlation coefficient > or =0.9). CONCLUSIONS: Descending corticospinal tracts diffusion-weighted MRI signal is predictive of motor outcome from neonatal arterial ischemic stroke. This accurate, reliable, and simple tool will impact decision making in acute neonatal stroke. PMID- 17272776 TI - Differential prognosis of isolated cortical swelling and hypoattenuation on CT in acute stroke. AB - BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a validated method of assessing parenchymal ischemic changes, including focal swelling and hypoattenuation. The hypothesis that these signs result from different pathophysiological processes was tested by comparing CT with diffusion and perfusion- weighted MRI. METHODS: MRI and CT were performed, within 2 hours of each other, in 30 ischemic stroke patients <17 hours after symptom onset. Relative apparent diffusion coefficient, relative cerebral blood flow, and relative cerebral blood volume were calculated for individual cortical ASPECTS regions. Regional infarction was assessed on days 3 to 5. RESULTS: Isolated focal swelling was seen in 25 ASPECTS cortical regions from 6 patients. Cortical hypoattenuation was observed in 25 regions from 11 patients. Median relative apparent diffusion coefficient was significantly lower in hypoattenuated regions (0.84; interquartile range, 0.66 to 0.91) relative to those with focal swelling (0.97; interquartile range, 0.91 to 1.01; P<0.001). Median relative cerebral blood flow in focal swelling regions (81.0%; interquartile range, 70.4 to 93.0) was similar to that of tissue that appeared normal on CT (71.8%; interquartile range, 47.1 to 94.5). In hypoattenuated regions, relative cerebral blood flow was significantly decreased (37.0%; interquartile range, 25.6 to 70.2; P=0.002). Median relative cerebral blood volume was increased (121.1%; interquartile range, 112.0 to 130.3) in focal swelling regions, relative to normal-appearing tissue (94.7%; interquartile range, 62.0 to 114.6; P<0.001), but decreased in hypoattenuated regions (58.9%; interquartile range, 47.5 to 92.7; P=0.012). Infarction occurred in all hypoattenuated regions, but only in 32% of those with focal swelling. CONCLUSIONS: Elevated relative cerebral blood volume and normal relative apparent diffusion coefficient in ASPECTS regions with focal swelling on CT is consistent with penumbral tissue. Isolated focal swelling is not always associated with infarction. These results support removal of focal swelling from the ASPECTS system. PMID- 17272777 TI - Prior statin use may be associated with improved stroke outcome after tissue plasminogen activator. AB - BACKGROUND AND PURPOSE: Statins may exert some neuroprotection, because use before stroke onset has been related to better outcome and reduced mortality. The purpose of this study was to evaluate whether patients who receive tissue plasminogen activator have better outcome when statins were taken before stroke. METHODS: We evaluated 145 patients with a stroke involving the middle cerebral artery (who received tissue plasminogen activator treatment (<3 hours). RESULTS: Fifty-eight patients (40%) became functionally independent at 3 months. Factors associated with good outcome were age (68 versus 74.4 years, P<0.001), baseline National Institutes of Health Stroke Scale score (13 versus 18, P<0.001), and proximal middle cerebral artery occlusion (56.1% versus 84.3%, P<0.001). Statins were the only drug taken before stroke that conditioned neurologic outcome. In fact, among patients who were functionally independent, 27.3% were under statins at the time of the index stroke as compared with 13.6% among the group of patients who were dependent or dead by the end of the study period (P=0.046). A logistic regression model identified baseline National Institutes of Health Stroke Scale score <15 (OR: 5.8, 95% CI: 2.05 to 16.36, P=0.001), age <70 years (OR: 2.93, 95% CI: 1.13 to 7.59, P=0.027), and previous treatment with statins (OR: 5.26, 95% CI: 1.48 to 18.72, P=0.027) as independent predictors of good functional outcome. CONCLUSIONS: Patients under statins at the moment of stroke who received thrombolytics had an improved neurologic outcome. PMID- 17272778 TI - Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischemia/reperfusion in rats: relation to blood brain barrier dysfunction. AB - BACKGROUND AND PURPOSE: Hyperglycemia is linked to a worse outcome after ischemic stroke. Among the manifestations of brain damage caused by ischemia are blood brain barrier (BBB) disruption and edema formation. Oxidative stress and matrix metalloproteinase-9 (MMP-9) activation are implicated in BBB dysfunction after ischemia/reperfusion injury. Our present study was designed to clarify the relation among hyperglycemia, oxidative stress, and MMP-9 activation associated with BBB dysfunction after transient focal cerebral ischemia (tFCI). METHODS: We used a model of 60 minutes of middle cerebral artery occlusion on the following animals: normoglycemic wild-type rats, wild-type rats with hyperglycemia induced by streptozotocin, and human copper/zinc superoxide dismutase (SOD1) transgenic rats with streptozotocin-induced hyperglycemia. We evaluated edema volume, Evans blue leakage, and oxidative stress, such as the carbonyl groups and oxidized hydroethidine (HEt), SOD activity, and gelatinolytic activity, including MMP-9. RESULTS: Hyperglycemia significantly increased edema volume and Evans blue leakage. Moreover, it enhanced the levels of the carbonyl groups, the oxidized HEt signals, and MMP-9 activity after tFCI without alteration in SOD activity. Gelatinolytic activity and oxidized HEt signals had a clear spatial relation in the hyperglycemic rats. SOD1 overexpression reduced the hyperglycemia-enhanced Evans blue leakage and MMP-9 activation after tFCI. CONCLUSIONS: Hyperglycemia increases oxidative stress and MMP-9 activity, exacerbating BBB dysfunction after ischemia/reperfusion injury. Superoxide overproduction may be a causal link among hyperglycemia, MMP-9 activation, and BBB dysfunction. PMID- 17272779 TI - Predictors of carotid intima-media thickness progression in young adults: the Bogalusa Heart Study. AB - BACKGROUND AND PURPOSE: We sought to evaluate the predictors of carotid intima media thickness (CIMT) progression in young adults and to determine whether they differed between the sexes. Although risk factors for the progression of atherosclerosis in middle-aged and elderly adults are well known, they are less well understood in young adults. CIMT is a validated measure of subclinical atherosclerosis. METHODS: B-mode ultrasound images of the far walls of both carotid arteries were obtained in 336 young adults in the Bogalusa Heart Study, whose mean+/-SD age was 32.3+/-3.0 years. CIMT and risk factors were measured at baseline (1995-1996) and after 5.8+/-0.6 years. Multivariable regression was used to determine the predictors of CIMT progression. RESULTS: CIMT progression rates in women (0.015+/-0.024 mm/y) and men (0.020+/-0.027 mm/y) were not statistically different after controlling for body mass index (P=0.155). Smoking was a statistically significant predictor of common and composite CIMT progression in both sexes. In men, systolic blood pressure was an independent predictor of internal carotid and composite CIMT progression, fasting glucose predicted common CIMT progression, and family history predicted composite CIMT progression. CONCLUSIONS: In young adults, smoking was a consistent predictor of short-term CIMT progression in men and women. Traditional risk factors also predicted CIMT progression in men. PMID- 17272780 TI - Arterial stiffness, cognitive decline, and risk of dementia: the Rotterdam study. AB - BACKGROUND AND PURPOSE: Arterial stiffness is associated with an increased risk of myocardial infarction and stroke, independent of classical vascular risk factors. Vascular factors and stroke are associated with cognitive function and dementia. We examined whether arterial stiffness was independently associated with cognitive function and dementia. METHODS: The present study was based on the Rotterdam Study, a prospective population-based cohort study ongoing since 1990. During the third examination (1997-1999) arterial stiffness was measured by assessment of pulse wave velocity and carotid distensibility. Cognitive function was assessed during the third and fourth examination (2002-2004) with a neuropsychological test battery. We used linear and logistic regression to estimate the association of arterial stiffness with cognitive function and cognitive decline. From the third examination until January 1, 2005, we identified 156 incident dementia cases. Cox proportional hazard models were used to estimate the association between arterial stiffness and the risk of dementia. RESULTS: After adjustment for cardiovascular risk factors we found an association of increased pulse wave velocity with poorer performance on the Stroop test (adjusted beta-coefficient [95% confidence interval] 1.13 [0.26 to 1.99] per standard deviation increase in pulse wave velocity) but not with performance on other cognitive tests. No associations were found between measures of arterial stiffness and cognitive decline or risk of dementia after adjustment for cardiovascular factors. CONCLUSIONS: We did not identify arterial stiffness as an independent risk factor of cognitive decline or risk of dementia. PMID- 17272781 TI - Composition of the stable carotid plaque: insights from a multidetector computed tomography study of plaque volume. AB - BACKGROUND AND PURPOSE: Calcification has been associated with carotid plaque stability; however, an acceptable in vivo method to define plaques based on this component remains to be developed. The purpose of our study was to compare calcified and noncalcified volumes of carotid artery culprit symptomatic plaques with asymptomatic plaques using multidetector computed tomography. METHODS: We identified 102 patients with > or =50% stenosis using NASCET criteria by multidetector computed tomography angiography between January 2004 and May 2006, which included 35 symptomatic (stenosis: 82.0+/-11.9%) and 67 asymptomatic patients (stenosis: 79.4+/-10.8%). Total plaque volume, noncalcified plaque volume, calcified plaque volume, and calcified/total ratio were measured for the 102 index plaques causing stenosis. RESULTS: In a model including age, stenosis, and cardiovascular risk factors, calcified plaque volume/total plaque volume was significantly inversely associated with the occurrence of symptoms (P=0.012; odds ratio, 0.047; 95% CI, 0.004 to 0.511). There was a notable overlap in the calcified plaque volume/total plaque volume ratio between 0% and 45% for symptomatic and asymptomatic plaques. However, calcification >45% of the total plaque was very specific: 97.1% (34/35) for absence of symptoms (sensitivity: 28.4% 19/67). No significant association between total plaque volume, noncalcified plaque volume, or calcified plaque volume and symptomatology was found. CONCLUSIONS: The proportion of carotid plaque calcification, rather than absolute volume, is associated with stability in patients with stenosis. Specifically, for a subset of patients, plaque calcification >45% of the total volume may represent a clinically useful cutoff. The carotid plaque calcium ratio, determined by multidetector computed tomography volume measurements, may help noninvasively risk stratify patients with asymptomatic stenosis. PMID- 17272783 TI - A comprehensive analysis of adverse obstetric and pediatric complications in women with asthma. AB - RATIONALE: Previous studies have raised concern that women with asthma have increased risks of adverse obstetric and pediatric complications, but these have generally been underpowered. OBJECTIVES: To quantify risks of major adverse pregnancy outcomes and obstetric complications in women with and without asthma. METHODS: We extracted information on 281,019 pregnancies from the Health Improvement Network database between 1988 and 2004. We analyzed the data using logistic regression. MEASUREMENTS AND MAIN RESULTS: In 37,585 pregnancies of women with asthma compared with 243,434 pregnancies of women without asthma, risks of stillbirth and therapeutic abortion were similar; however, the risk of miscarriage was slightly higher (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.06-1.13). Risks of most obstetric complications (placental abruption, placental insufficiency, placenta previa, preeclampsia, hypertension, gestational diabetes, thyroid disorders in pregnancy, and assisted delivery) were not higher in pregnancies of women with asthma compared with those without asthma, with the exception of increases in antepartum (OR, 1.20; 95% CI, 1.08-1.34) or postpartum (OR, 1.38; 95% CI, 1.21-1.57) hemorrhage, anemia (OR, 1.06; 95% CI, 1.01-1.12), depression (OR, 1.52; 95% CI, 1.36-1.69), and caesarean section (OR, 1.11; 95% CI, 1.07-1.16). Risks of miscarriage, depression, and caesarean section increased moderately in women with more severe asthma and previous asthma exacerbations. CONCLUSIONS: We found some increased risks in women with asthma that need to be considered in the future; however, our results indicate that women with asthma have similar reproductive risks compared with women without asthma in the general population for most of the range of outcomes studied. PMID- 17272784 TI - How prostacyclin improves cardiac output in right heart failure in conjunction with pulmonary hypertension. AB - RATIONALE: Prostacyclin therapy improves patients with pulmonary arterial hypertension, but whether this is attributable to an improved inotropic state of the right ventricle in addition to a decreased pulmonary arterial pulmonary vascular resistance remains unclear. OBJECTIVES: We measured the effects of prostacyclin on load-independent measurements of right ventricular contractility in a model of load-induced acute right ventricular failure. METHODS AND RESULTS: Persistent right ventricular failure was induced in dogs by a transient (90 min) pulmonary arterial constriction. After constriction release and stabilization, intravenous prostacyclin (epoprostenol) was given at doses of 6 and 12 ng/kg/minute for 30 minutes. Pulmonary vascular resistance was assessed by pressure-flow relationships and right ventricular afterload by effective pulmonary arterial elastance. Right ventricular contractility was estimated by end-systolic elastance and right ventriculoarterial coupling efficiency by the ratio of these elastances. Transient pulmonary arterial constriction persistently increased pulmonary vascular resistance, increased arterial elastance from 1.00 +/- 0.07 to 2.86 +/- 0.26 mm Hg/ml, decreased end-systolic elastance from 1.11 +/ 0.07 to 0.54 +/- 0.02 mm Hg/ml, decreased the ratio of elastances from 1.14 +/- 0.08 to 0.20 +/- 0.02, and cardiac output from 4.6 +/- 0.1 to 2.3 +/- 0.1 L/min (p < 0.05). Epoprostenol did not affect end-systolic elastance; however, it decreased arterial elastance to 1.84 +/- 0.33 mm Hg/ml, and increased the ratio of elastances to 0.46 +/- 0.17 and cardiac output to 3.4 +/- 0.3 L/min (p < 0.05). CONCLUSIONS: In this model of afterload-induced right ventricular failure, prostacyclin improves right ventriculoarterial coupling and cardiac output because of vasodilating effects. PMID- 17272782 TI - Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. AB - Bronchopulmonary dysplasia and emphysema are significant global health problems at the extreme stages of life. Both are characterized by arrested alveolar development or loss of alveoli, respectively. Both lack effective treatment strategies. Knowledge about the genetic control of branching morphogenesis in mammals derives from investigations of the respiratory system in Drosophila, but mechanisms that regulate alveolar development remain poorly understood. Even less is known about regulation of the growth and development of the pulmonary vasculature. Understanding how alveoli and the underlying capillary network develop, and how these mechanisms are disrupted in disease states, are critical for developing effective therapies for lung diseases characterized by impaired alveolar structure. Recent observations have challenged old notions that the development of the blood vessels in the lung passively follows that of the airways. Rather, increasing evidence suggests that lung blood vessels actively promote alveolar growth during development and contribute to the maintenance of alveolar structures throughout postnatal life. Our working hypothesis is that disruption of angiogenesis impairs alveolarization, and that preservation of vascular growth and endothelial survival promotes growth and sustains the architecture of the distal airspace. Furthermore, the explosion of interest in stem cell biology suggests potential roles for endothelial progenitor cells in the pathogenesis or treatment of lung vascular disease. In this Pulmonary Perspective, we review recent data on the importance of the lung circulation, specifically examining the relationship between dysmorphic vascular growth and impaired alveolarization, and speculate on how these new insights may lead to novel therapeutic strategies for bronchopulmonary dysplasia. PMID- 17272785 TI - Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction. AB - RATIONALE: Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular diseases. Injury of endothelial cells has been advanced as an initial trigger to atherosclerosis. OBJECTIVES: To study the association between circulating apoptotic endothelial cells and vasomotor dysfunction as a function of sleep apnea. METHODS: Brachial artery flow-mediated dilation was determined in 14 subjects with documented OSA and 10 healthy control subjects at baseline and 8 weeks after continuous positive airway pressure (CPAP) therapy. Quantification of circulating apoptotic endothelial cells (CD146(+) Annexin V(+)) was performed by flow cytometry. MEASUREMENTS AND MAIN RESULTS: Compared with healthy subjects, patients with OSA had higher numbers of circulating CD146(+) Annexin V(+) cells (39.2 +/- 13.6 cells/mL and 17.8 +/- 9.4, respectively; p < 0.001). Increased apoptotic endothelial cells correlated moderately with abnormal vascular function (r = -0.61; p = 0.001). A significant correlation was observed between CD146 Annexin V(+) cells and the apnea-hypopnea index (r = 0.56; p = 0.004). After 8 weeks of treatment with CPAP, the numbers of circulating apoptotic endothelial cells were reduced significantly from 39.2 +/- 13.6 to 22.3 +/- 12.9 apoptotic cells per milliliter (p < 0.001) and correlated with improvement in endothelium dependent vasodilation (r = 0.49; p = 0.07). CONCLUSIONS: In patients with OSA, impairment of endothelial-dependent vasodilation correlated with the degree of endothelial cell apoptosis. CPAP therapy led to significant decline in circulating apoptotic endothelial cells. These findings provide an additional mechanism for the predisposition of patients with OSA to premature vascular disease. PMID- 17272787 TI - Remodeling and airway hyperresponsiveness but not cellular inflammation persist after allergen challenge in asthma. AB - RATIONALE: Airway hyperresponsiveness (AHR) increases up to 2 weeks after allergen inhalational challenge of subjects with asthma who show a late-phase asthmatic reaction (dual responders). Cellular inflammation and airway remodeling are increased 24 hours after allergen challenge. OBJECTIVES: To determine whether persistence of increased AHR is associated with persistent activation of remodeling and enhanced inflammation. METHODS: Fiberoptic bronchoscopy was performed at baseline and at 24 hours and 7 days after allergen inhalational challenge of dual responders with mild-moderate asthma. At each time point, AHR, spirometry, and expression of tenascin (extracellular matrix protein), procollagen I, procollagen III, and heat shock protein (HSP)-47 (markers of collagen synthesis), and alpha-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of airway remodeling, together with numbers of mucosal major basic protein-positive eosinophils, CD68(+) macrophages, CD3(+), CD4(+), CD8(+) T cells, elastase-positive neutrophils, and tryptase-positive mast cells. MEASUREMENTS AND MAIN RESULTS: AHR was increased from baseline at 24 hours and 7 days after allergen challenge. Reticular basement membrane tenascin expression was elevated at 24 hours and returned to baseline levels at 7 days. Reticular basement membrane procollagen III expression was significantly elevated at 7 days. Expression of procollagen I, HSP-47, and alpha-smooth muscle actin were all higher at 7 days compared with 24 hours. At 24 hours, eosinophil, macrophage, neutrophil, and CD3(+) T cells were increased but had returned to baseline by 7 days. CONCLUSIONS: In dual responders with asthma, the 24-hour increase in airway wall cellular inflammation after allergen challenge resolves by 7 days, whereas the increases in AHR and markers of remodeling persist. PMID- 17272786 TI - Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. AB - RATIONALE AND OBJECTIVES: Although many clinical physiology and epidemiology studies show an association between obstructive sleep apnea (OSA) and markers of insulin resistance, no causal pathway has been established. The purpose of the current study was to determine if the intermittent hypoxia (IH) stimulus that characterizes OSA causes insulin resistance in the absence of obesity. Furthermore, we assessed the impact of IH on specific metabolic function in liver and muscle. Finally, we examined the potential mechanistic role of the autonomic nervous system (ANS) in mediating insulin resistance in response to IH. METHODS AND RESULTS: Hyperinsulinemic euglycemic clamps were conducted and whole-body insulin sensitivity, hepatic glucose output, and muscle-specific glucose utilization assessed in conscious, chronically instrumented adult male C57BL/6J mice exposed to (1) IH (achieving a nadir of Fi(O(2)) = 5-6% at 60 cycles/h for 9 h), (2) intermittent air as a control, (3) IH with ANS blockade (hexamethonium), or (4) IA with ANS blockade. IH decreased whole-body insulin sensitivity compared with intermittent air (38.8 +/- 2.7 vs. 49.4 +/- 1.5 mg/kg/min, p < 0.005) and reduced glucose utilization in oxidative muscle fibers, but did not cause a change in hepatic glucose output. Furthermore, the reduction in whole-body insulin sensitivity during IH was not restored by ANS blockade. CONCLUSION: We conclude that IH can cause acute insulin resistance in otherwise lean, healthy animals, and that the response is associated with decreased glucose utilization of oxidative muscle fibers, but that it occurs independently of activation of the ANS. PMID- 17272788 TI - Low bone mineral density in young children with cystic fibrosis. AB - RATIONALE: Low bone mineral density (BMD) is a frequent problem for adult patients with cystic fibrosis (CF). Only limited information is available for young patients. OBJECTIVES: The aim of this study was to evaluate BMD of children with CF younger than 6 years. METHODS: BMD was measured at the lumbar spine (LS) after adjustment for height, sex, and pubertal status in 25 children with CF younger than 6 years, 53 prepubertal children aged 6 to 10 years, and 36 adolescents aged 11 to 18 years. Nutritional status, body composition, pulmonary disease severity, corticosteroid usage, dietary calcium, caloric intake, and vitamin D status were evaluated as potential correlates of BMD. MEASUREMENTS AND MAIN RESULTS: The mean LS z score in the youngest group was significantly lower than normal (-0.96; SEM, 0.3). It did not differ significantly from that of children aged 6 to 10 years (-0.91; SEM, 0.2) or adolescents (-1.4; SEM, 0.2). LS z score was positively correlated with fat-free mass in multiple regression analysis. LS z score was less than -1 in 34% of the patients with mild pulmonary disease and normal nutritional status. CONCLUSIONS: These data suggest that the origin of CF bone disease in early childhood may be independent of nutritional status or disease severity. PMID- 17272790 TI - Predictability of outcomes: chaos theory and diabetes education. PMID- 17272791 TI - AADE position statement. Cultural sensitivity and diabetes education: recommendations for diabetes educators. PMID- 17272792 TI - AADE position statement. Individualization of diabetes self-management education. PMID- 17272793 TI - The physiology of incretin hormones and the basis for DPP-4 inhibitors. AB - With the rising prevalence of diabetes, new therapies that provide glucose control are needed. Although many medications are available, tight glucose control is still a challenge. In this article, the physiology of glucose homeostasis is explored with respect to type 2 diabetes. The incretin effect is explained in detail, and the incretin hormones, glucose-dependent insulinotrophic polypeptide and glucagon-like peptide 1, are investigated as well as their contribution to type 2 diabetes therapy. Studies involving dipeptidyl-peptidase 4 (DPP-4) inhibitors are summarized as to their effects on glucose homeostasis. Specifically, vildagliptin (Galvus; Novartis International AG, Basel, Switzerland) and sitagliptin (Januvia; Merck & Co, Inc, Whitehouse Station, NJ) are described. The use and efficacy of the currently available incretin mimetic, exenatide (Byetta; Amylin Pharmaceuticals, Inc and Eli Lilly and Company, San Diego, Calif, and Indianapolis, Ind), are briefly discussed. Throughout this article, the rationale for the use of DPP-4 inhibitors is presented. PMID- 17272794 TI - Adapting the Diabetes Prevention Program lifestyle intervention for delivery in the community: the YMCA model. AB - The Diabetes Prevention Program (DPP) demonstrated that a structured diet and physical activity intervention that achieves and maintains modest weight loss for overweight adults with impaired glucose tolerance can significantly reduce the development of diabetes. Although tens of millions of American adults could benefit from access to the DPP lifestyle intervention, there currently is no available model for nationwide dissemination of this highly beneficial and cost effective approach to diabetes prevention. In this article, the authors describe the evolution of adaptations to improve DPP lifestyle intervention implementation and dissemination by a strong community partner, the YMCA. They also provide information about early field research and an ongoing clinical trial that will provide information about the feasibility and effectiveness of applying this new model on a national scale. PMID- 17272795 TI - The Robert Wood Johnson Foundation Diabetes Initiative: demonstration projects emphasizing self-management. AB - PURPOSE: The purpose of the Diabetes Initiative of the Robert Wood Johnson Foundation is to demonstrate feasible and sustainable approaches to promoting diabetes self-management in primary care and community settings. METHODS: The Diabetes Initiative of the Robert Wood Johnson Foundation includes 14 demonstration projects in primary care settings and in community-clinical partnerships. Projects serve predominantly indigent populations from varied cultural and linguistic backgrounds in urban, rural, and frontier settings around the United States. This report describes the Initiative, its ecological perspective on self-management, and implications for program development, sustainability, and dissemination. RESULTS: Ecological perspectives stress varied levels of influence ranging from individuals to communities and policies. Based on this, the Initiative has identified key resources and supports for self management (individualized assessment, collaborative goal setting, enhancing skills, follow-up and support, community resources, and continuity of quality clinical care). Lessons learned include the central roles of community health workers, integration of healthy coping and attention to negative emotion and depression in self-management, community partnerships, approaches to ongoing follow-up and support, organizational factors in sustaining programs, and the utility of a collaborative learning network for program development. Sustainability stresses organizational and policy supports for the program. Dissemination of lessons learned will stress collaboration among interested parties, stimulating consumer understanding and demand for self-management services as central to diabetes care. CONCLUSIONS: The Diabetes Initiative demonstrates that effective self-management programs and supports can be implemented in real-world clinical and community settings, providing models of worthwhile, sustainable programs. PMID- 17272796 TI - Measuring comparative risk perceptions in an urban minority population: the risk perception survey for diabetes. AB - PURPOSE: The purpose of this study was to assess comparative risk perceptions related to diabetes complications and their associations with patient characteristics in an urban minority sample. METHODS: The authors developed the Risk Perception Survey-Diabetes Mellitus (RPS-DM) and administered the survey using a Solomon Four group design with a random half of a sample of 599 adults with diabetes. This was the baseline survey to measure comparative risk perceptions in a multiethnic sample prior to implementation of randomly assigned behavioral interventions to improve diabetic retinopathy screening rates. RESULTS: The RPS-DM survey was completed by 250 participants (an 85% completion rate). Participants did not differ significantly by demographics from all other subjects. The sample included 62% women, mean age of 56.5 years, 42.4% Hispanic ethnicity, and 44% black race. The survey showed acceptable psychometric properties in English or Spanish and was feasible to complete by telephone in 12 to 15 minutes. Significant differences by subject characteristics were seen in several survey subscales, including Risk Knowledge by age (P < or = .01) and annual income (P < or = .05), Personal Control by educational level (P < or = .05), and Optimistic Bias by birthplace (P < or = .05) and educational level (P < or = .01). An analysis of variance produced demographic models statistically significant (P < .05) for Risk Knowledge, Personal Control, Environmental Risk, and Optimistic Bias. From 13% to 16% of the variance in the subscale scores was explained by these demographic models. CONCLUSIONS: The RPS-DM is the first instrument to measure comparative risk perceptions, including knowledge related to diabetes complications. These data are important for educators and researchers who wish to assess risk perceptions and tailor health/risk communications for their diabetes populations. PMID- 17272797 TI - Efficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy. AB - PURPOSE: The purpose of this article is to review current evidence available for alpha-lipoic acid (ALA) and its ability to improve symptoms of peripheral diabetic neuropathy (PDN). METHODS: This article searched MEDLINE from 1966 to November 2005 to identify clinical trials that supplemented ALA to individuals with type 1 or type 2 diabetes and positive sensory symptoms of PDN. Clinical trials to be included in this review met specific criteria of randomization, double masking, and placebo-controlled design. RESULTS: The search results produced 5 clinical trials that met the prerequisites for this review. ALA appears to improve neuropathic symptoms and deficits when administered via parenteral supplementation over a 3-week period. Oral treatment with ALA appears to have more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone. An oral regimen of ALA and optimal length of treatment remains unclear. Both parenteral and up to a 2-year time period of oral supplementation of ALA appears to be safe without affecting glycemic control. CONCLUSIONS: Based on these results, ALA should be considered as a treatment option for patients with PDN. When discussing supplementation with patients, it is important to discuss potential side effects; vitamin, mineral, and drug interactions; and current evidence available regarding efficacy. PMID- 17272798 TI - Multidisciplinary group behavioral and pharmacologic intervention for cardiac risk reduction in diabetes: a pilot study. AB - PURPOSE: The purpose of this study was to evaluate the effectiveness of a multidisciplinary team providing both education and medication management in a group setting for cardiac risk reduction in patients with diabetes mellitus. METHODS: The electronic medical records of patients with diabetes who participated in group behavioral and pharmacologic interventions for cardiac risk reduction during May to October 2002 at the Providence VA Medical Center were reviewed. Forty-one veterans with diabetes mellitus attended the weekly sessions of a diabetes education and intervention program directed by pharmacists for 1 month. Two groups of 15 to 20 patients received four 1.5-hour diabetes self management education classes provided by a multidisciplinary team consisting of a pharmacist (leader), nurse educator, dietician, physical therapist, and social worker and four 1-hour group medication adjustment sessions provided by the pharmacist. Pharmacists followed medication adjustment algorithms for blood pressure, diabetes, and cholesterol management previously developed in collaboration with physician specialists in the field. Baseline and 3-month after intervention data were collected for glycosylated hemoglobin A1C (A1C), systolic and diastolic blood pressure (SBP and DBP, respectively), low-density lipoprotein cholesterol, and body mass index. RESULTS: Thirty-six patients attended 4 sessions, and 5 patients attended 3 sessions. All parameters improved after the intervention, with significant reductions in A1C (-1.5% +/- 1.0%) and DBP (-5 mm Hg). Reductions were further accentuated when baseline values were abnormal, with significant improvement in A1C (-2.0% +/- 0.5%), SBP (-14 +/- 3 mm Hg), and DBP ( 13 +/- 3 mm Hg). CONCLUSIONS: Short-term multidisciplinary group behavioral and pharmacologic intervention programs may be effective in improving cardiac risk factors in patients with diabetes. PMID- 17272799 TI - Physical activity and type 2 diabetes: exploring the role of gender and income. AB - PURPOSE: The purpose of this study was to explore (1) patterns in physical activity behaviors and (2) the meaning and personal significance of social cognitive theory (SCT) constructs on physical activity, across gender and income groups among people with type 2 diabetes (T2DM). METHODS: Albertans, 18 years and older (x- = 63, SD = 12.08) with T2DM (N = 1614) completed self-report measures of demographic characteristics and physical activity. Two-way, between-groups analyses of variance (ANOVAs) assessed main and interaction effects of gender and income on leisure time physical activity (LTPA). A subsample of these participants (n = 20) subsequently completed qualitative telephone interviews to provide contextual understanding of the quantitative data and to explore salient SCT influences on physical activity. RESULTS: Significant findings indicated that men participate in more LTPA than women do, and those from the highest income group participate in more LTPA than low- or middle-income groups (P < .01). Interview results suggested that walking is the most popular form of physical activity; however, gender and income groups differ in other leisure and nonleisure physical activities. Furthermore, patterns for SCT constructs related to physical activity were apparent across gender and income, most noticeably for self-efficacy and environmental and situational influences. Specifically among men, noteworthy differences existed between income groups for self-control and reinforcement strategies. CONCLUSIONS: The study highlights the need for more sensitive self-report measures and objective measures of physical activity to help distinguish whether true differences exist between certain demographic groups. Moreover, interventions that promote walking may be beneficial for people with T2DM, provided that appropriate environmental and policy changes occur to accommodate walking and other physical activity behaviors. PMID- 17272800 TI - The relationship between health literacy and diabetes knowledge and readiness to take health actions. AB - PURPOSE: The purpose of this study was to explore the relationship among health literacy, patients' readiness to take health actions, and diabetes knowledge among individuals with type 2 diabetes. METHODS: Sixty-eight patients with type 2 diabetes receiving care in an academic general internal medicine clinic were administered the Rapid Estimate of Adult Literacy in Medicine (REALM) literacy instrument prior to completing the Diabetes Health Belief Model (DHBM) scale and Diabetes Knowledge Test (DKT). Multivariable linear regression was used to assess the association between REALM literacy level, DKT score, DHBM scale score, and most recent hemoglobin A1C level while controlling for other covariates of interest. RESULTS: After controlling for other covariates of interest, no significant association between DHBM scale score and REALM literacy level was found (P = .29). However, both DKT score and most recent hemoglobin A1Clevel were found to be significantly associated with patient literacy (P = .004 and P = .02, respectively). Based on the multivariable model, patients with less than a fourth grade literacy level had 13% lower DKT scores (95% confidence interval [CI], -28% to -2%; P = .08) and 1.36% higher most recent hemoglobin A1Clevels (95% CI, 1.06% to 1.73%; P = .02) relative to those with a high school literacy level. CONCLUSIONS: Low health literacy is a problem faced by many patients that affects their ability to navigate the health care system and manage their chronic illnesses. While low health literacy was significantly associated with worse glycemic control and poorer disease knowledge in patients with type 2 diabetes, there was no significant relationship with their readiness to take action in disease management. PMID- 17272801 TI - US nurses' perceptions of their role in diabetes care: results of the cross national Diabetes Attitudes Wishes and Needs (DAWN) study. AB - PURPOSE: The purpose of this study was to examine nurse and physician perceptions of nurse involvement and roles in diabetes care. METHODS: The study used a cross sectional design with face-to-face or telephone interviews of diabetes health care professionals in 13 countries from Asia, Australia, Europe, and North America. This article focuses on the data from US health care providers. The US sample included 51 generalist nurses, 50 diabetes specialist nurses, 166 generalist physicians, and 50 diabetes specialist physicians. RESULTS: Nurses and physicians agreed that nurses should take a larger role in managing diabetes. Most common differences identified between nurses and physicians were that nurses provide better education, spend more time with patients, were better listeners, and knew their patients better than physicians. All nurses had a high perceived need for better understanding of psychosocial issues and were more likely than physicians to suggest helping patients to take responsibility for their care. Nurses more than physicians also said better communication was needed. Generalist nurses report that they act as intermediaries and facilitate patient appointment keeping. Specialist nurses talk to patients about self-management, teach medication management, have a higher level of involvement in medication prescribing, and are more willing to take on additional responsibilities than generalist nurses. CONCLUSIONS: There is an increased need for more involvement by nurses, particularly specialist nurses, in diabetes care. PMID- 17272803 TI - Case study 1: exploring the pharmacologic agents for treatment of type 2 diabetes. PMID- 17272804 TI - Case study 2: new insights: clinical pearls for using incretin mimetics in type 2 diabetes. PMID- 17272805 TI - Case study 3: balancing act: using a team approach to achieve better glycemic control for the patient with type 2 diabetes. PMID- 17272806 TI - Angiogenic role of LYVE-1-positive macrophages in adipose tissue. AB - Here we report the discovery of a characteristic dense vascular network (DVN) in the tip portion of epididymal adipose tissue in adult mice. The DVN is formed by angiogenesis rather than by vasculogenesis, and has functional blood circulation. This DVN and its subsequent branching may provide a new functional route for adipogenesis. The recruitment, infiltration, and accumulation of bone marrow derived LYVE-1(+) macrophages in the tip region are crucial for the formation of the DVN. Matrix metalloproteinases (MMPs) and the VEGF-VEGFR2 system are responsible not only for the formation of the DVN, but also for the recruitment and infiltration of LYVE-1(+) macrophages into the epididymal adipose tissue tip region. SDF-1, but not the MCP-1-CCR2 system, is a critical factor in recruitment and ongoing retention of macrophages in this area. We also demonstrate that the tip region of epididymal adipose tissue is highly hypoxic, and thus provides a microenvironment conducive to the high expression and enhanced activities of VEGF, VEGFR2, MMPs, and SDF-1 in autocrine and paracrine manners, to create an ideal niche for the recruitment, retention, and angiogenic action of macrophages. These findings shed light on the complex interplay between macrophage infiltration, angiogenesis, and adipogenesis in the tip region of adult epididymal adipose tissue, and provide novel insight into the regulation of alternative outgrowth of adipose tissue. PMID- 17272807 TI - Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia. AB - Circulating progenitor cells home to sites of postnatal neovascularization and differentiate into endothelial cells but questions remain regarding the source of these cells. Indeed, a recent study suggests that nonbone marrow-derived cells may be even more important than bone marrow-derived cells in the setting of transplant arteriosclerosis. Thus, we aimed to thoroughly investigate the contribution of nonbone marrow-derived progenitor cells for neovascularization. We exclusively identified nonbone marrow-derived progenitor cells by combining a parabiosis model with reverse bone marrow transplantation followed by hindlimb ischemia. In this model, nonbone marrow-derived circulating progenitor cells attributed for 74+/-13% of the circulating progenitor cells that incorporated into the ischemic hindlimb. Increasing evidence suggests that organs such as small intestine and liver contain a considerable number of tissue resident progenitor cells and, thus, represent putative sources for nonbone marrow-derived progenitors. To track organ-derived progenitors, we transplanted sex-mismatched small intestine or liver, respectively, into rats followed by induction of hindlimb ischemia. These experiments show that organ-derived progenitor cells are contributing to postnatal vasculogenesis (intestine: 4.7+/-3.7%; liver: 6.3+/ 2.2%). Based on the subsequent observation that liver-derived nonhematopoietic c kit(+)CD45(-) progenitors are mobilized on induction of hindlimb ischemia, we prospectively isolated and intravenously infused these progenitors from murine livers. The isolated cells demonstrated a marked capacity for enhancing neovascularization and restoring blood flow to the ischemic hindlimb (no cells: 26.4+/-4.8% of normal blood flow; c-kit(+)CD45(-) cells: 67.0+/-8.0% of normal flow; P<0.01). In conclusion, we find that nonbone marrow-derived c-kit(+)CD45(-) progenitors contribute to postnatal neovascularization to an extent that is similar to that of bone marrow-derived progenitor cells. Intestine and liver represent a rich source for mobilized tissue-residing progenitor cells. PMID- 17272808 TI - Regulation of endothelial cell cycle by laminar versus oscillatory flow: distinct modes of interactions of AMP-activated protein kinase and Akt pathways. AB - Steady laminar flow in the straight parts of the arterial tree is atheroprotective, whereas disturbed flow with oscillation in branch points and the aortic root are athero-prone, in part, because of the distinct roles of the flow patterns in regulating the cell cycle of vascular endothelial cells (ECs). To elucidate the molecular basis underlying the endothelial cell cycle regulated by distinct flow patterns, we conducted flow-channel experiments to investigate the effects of laminar versus oscillatory flows on activation of AMP-activated protein kinase (AMPK) and Akt in ECs. Laminar flow caused a transient activation of both AMPK and Akt, but oscillatory flow activated only Akt, with AMPK being maintained at its basal level. Constitutively active and dominant-negative mutants of AMPK and Akt were used to elucidate further the positive effect of Akt and negative role of AMPK in mediating mTOR (mammalian target of rapamycin) and its target p70S6 kinase (S6K) in response to laminar and oscillatory flows. Measurements of phosphorylation of mTOR Ser2448 and S6K Thr389 showed that AMPK, by counteracting Akt under laminar flow, resulted in a transient activation of S6K. Under oscillatory flow, because of the lack of AMPK activation to effect negative regulation, S6K was activated in a sustained manner. As a functional consequence, AMPK activation attenuated cell cycle progression in response to both laminar and oscillatory flows. In contrast, AMPK inhibition promoted EC cycle progression by decreasing the cell population in the G(0)/G(1) phase and increasing it in the S+G(2)/M phase. In vivo, phosphorylation of the promitotic S6K in mouse thoracic aorta was much less than that in mouse aortic root. In contrast, AMPK phosphorylation was higher in the thoracic aorta. These results provide a molecular mechanism by which laminar versus oscillatory flow regulates the endothelial cell cycle. PMID- 17272809 TI - Adolescent feline heart contains a population of small, proliferative ventricular myocytes with immature physiological properties. AB - Recent studies suggest that rather than being terminally differentiated, the adult heart is a self-renewing organ with the capacity to generate new myocytes from cardiac stem/progenitor cells (CS/PCs). This study examined the hypotheses that new myocytes are generated during adolescent growth, to increase myocyte number, and these newly formed myocytes are initially small, mononucleated, proliferation competent, and have immature properties. Ventricular myocytes (VMs) and cKit(+) (stem cell receptor) CS/PCs were isolated from 11- and 22-week feline hearts. Bromodeoxyuridine incorporation (in vivo) and p16(INK4a) immunostaining were measured to assess myocyte cell cycle activity and senescence, respectively. Telomerase activity, contractions, Ca(2+) transients, and electrophysiology were compared in small mononucleated (SMMs) and large binucleated (LBMs) myocytes. Heart mass increased by 101% during adolescent growth, but left ventricular myocyte volume only increased by 77%. Most VMs were binucleated (87% versus 12% mononucleated) and larger than mononucleated myocytes. A greater percentage of SMMs was bromodeoxyuridine positive (SMMs versus LBMs: 3.1% versus 0.8%; P<0.05), and p16(INK4a) negative and small myocytes had greater telomerase activity than large myocytes. Contractions and Ca(2+) transients were prolonged in SMMs versus LBMs and Ca(2+) release was disorganized in SMMs with reduced transient outward current and T-tubule density. The T-type Ca(2+) current, usually seen in fetal/neonatal VMs, was found exclusively in SMMs and in myocytes derived from CS/PC. Myocyte number increases during adolescent cardiac growth. These new myocytes are initially small and functionally immature, with patterns of ion channel expression normally found in the fetal/neonatal period. PMID- 17272810 TI - Muscle ring finger 1, but not muscle ring finger 2, regulates cardiac hypertrophy in vivo. AB - Muscle ring finger (MuRF) proteins have been implicated in transmitting mechanical forces to cell signaling pathways through their interactions with the giant protein titin. Recent evidence has linked mechanically-induced stimuli with the control of serum response factor activity and localization through MuRF2. This observation is particularly intriguing in the context of cardiac hypertrophy, where serum response factor transactivation is a key event necessary for the induction of cardiac hypertrophy in response to increased afterload. We have previously reported that MuRF1, which is also a titin-associated protein, exerts antihypertrophic activity in vitro. In the present study, we induced cardiac hypertrophy in mice lacking MuRF1 and MuRF2 to distinguish the physiologic role of these divergent proteins in vivo. We identified for the first time that MuRF1, but not MuRF2, plays a key role in regulating the induction of cardiac hypertrophy, likely by its direct interactions with serum response factor. These studies describe for the first time distinct and nonoverlapping functional characteristics of MuRF1 and MuRF2 in response to cardiac stress in vivo. PMID- 17272812 TI - Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. AB - Circulating endothelial progenitor cells (EPCs) may contribute to endothelial regeneration; however, the exact mechanisms of their arterial homing remain elusive. We examined the role of the angiogenic chemokine receptor CXCR2 in the homing of human EPCs. Isolated EPCs expressed CXCR2 together with kinase insert domain-containing receptor, CD31, vascular endothelial cadherin, and CXCR4. Adhesion assays under flow conditions showed that EPCs preferentially adhered to beta(2)-integrin ligands, that firm arrest on fibronectin or fibrinogen was enhanced by the CXCR2 ligands CXCL1 or CXCL7, and that blockade of CXCR2 significantly reduced EPC adhesion on platelet-coated endothelial matrix. This was corroborated by the involvement of CXCR2 in EPC recruitment to denuded areas of murine carotid arteries ex vivo and in vivo. Notably, blocking CXCR2 inhibited the incorporation of human EPCs expressing CXCR2 at sites of arterial injury in athymic nude mice. Immunoreactivity for the beta-thromboglobulin isoform CXCL7 was observed in murine platelets and denuded smooth muscle cells (SMCs) early after wire injury, and transcripts for CXCL7 and CXCL1 were detected in isolated human arterial SMCs. Human KDR(+)CXCR2(+) cells showed better in situ adhesion to injured murine carotid arteries than KDR(+)CXCR2(-) cells, were predominantly CD14(+), and improved CXCR2-dependent endothelial recovery after injury in nude mice. In conclusion, our data clearly demonstrate the importance of CXCR2 for the homing of circulating EPCs to sites of arterial injury and for endothelial recovery in vivo. PMID- 17272811 TI - Activation of extracellular signal-regulated kinase 5 reduces cardiac apoptosis and dysfunction via inhibition of a phosphodiesterase 3A/inducible cAMP early repressor feedback loop. AB - Substantial evidence suggests that the progressive loss of cardiomyocytes caused by apoptosis significantly contributes to the development of heart failure. beta Adrenergic receptor activation and subsequent persistent phosphodiesterase 3A (PDE3A) downregulation and concomitant inducible cAMP early repressor (ICER) upregulation (PDE3A/ICER feedback loop) has been proposed to play a key role in the pathogenesis of cardiomyocyte apoptosis. In contrast, insulin-like growth factor-1 can activate cell survival pathways, providing protection against cell death and restoring muscle function. In this study, we found that insulin-like growth factor-1 activates extracellular signal-regulated kinase 5 (ERK5) and inhibits PDE3A/ICER feedback loop. Insulin-like growth factor-1 normalized isoproterenol-mediated PDE3A downregulation and ICER upregulation via ERK5/MEF2 activation, and also inhibited isoproterenol-induced myocyte apoptosis. To determine the physiological relevance of ERK5 activation in regulating PDE3A/ICER feedback loop, we investigated the PDE3A/ICER expression and cardiomyocyte apoptosis in transgenic mice with cardiac specific expression of a constitutively active form of mitogen-activated protein (MAP)/extracellular signal-regulated protein kinase (ERK) kinase 5alpha (MEK5alpha) (CA-MEK5alpha-Tg). In wild-type mice, pressure overload- or doxorubicin-induced significant reduction of PDE3A expression and subsequent ICER induction. Cardiac specific expression of CA MEK5alpha rescued pressure overload- or doxorubicin-mediated PDE3A downregulation and ICER upregulation and inhibited myocyte apoptosis as well as subsequent cardiac dysfunction in vivo. These data suggest that preventing the feedback loop of PDE3A/ICER by ERK5 activation could inhibit progression of myocyte apoptosis as well as cardiac dysfunction. These data suggest a new therapeutic paradigm for end stage of heart failure by inhibiting the PDE3A/ICER feedback loop via activating ERK5. PMID- 17272813 TI - Conditional neuronal nitric oxide synthase overexpression impairs myocardial contractility. AB - The role of the neuronal NO synthase (nNOS or NOS1) enzyme in the control of cardiac function still remains unclear. Results from nNOS(-/-) mice or from pharmacological inhibition of nNOS are contradictory and do not pay tribute to the fact that probably spatial confinement of the nNOS enzyme is of major importance. We hypothesize that the close proximity of nNOS and certain effector molecules like L-type Ca(2+)-channels has an impact on myocardial contractility. To test this, we generated a new transgenic mouse model allowing conditional, myocardial specific nNOS overexpression. Western blot analysis of transgenic nNOS overexpression showed a 6-fold increase in nNOS protein expression compared with noninduced littermates (n=12; P<0.01). Measuring of total NOS activity by conversion of [(3)H]-l-arginine to [(3)H]-l-citrulline showed a 30% increase in nNOS overexpressing mice (n=18; P<0.05). After a 2 week induction, nNOS overexpression mice showed reduced myocardial contractility. In vivo examinations of the nNOS overexpressing mice revealed a 17+/-3% decrease of +dp/dt(max) compared with noninduced mice (P<0.05). Likewise, ejection fraction was reduced significantly (42% versus 65%; n=15; P<0.05). Interestingly, coimmunoprecipitation experiments indicated interaction of nNOS with SR Ca(2+)ATPase and additionally with L-type Ca(2+)- channels in nNOS overexpressing animals. Accordingly, in adult isolated cardiac myocytes, I(Ca,L) density was significantly decreased in the nNOS overexpressing cells. Intracellular Ca(2+) transients and fractional shortening in cardiomyocytes were also clearly impaired in nNOS overexpressing mice versus noninduced littermates. In conclusion, conditional myocardial specific overexpression of nNOS in a transgenic animal model reduced myocardial contractility. We suggest that nNOS might suppress the function of L-type Ca(2+)-channels and in turn reduces Ca(2+)-transients which accounts for the negative inotropic effect. PMID- 17272814 TI - Pinch1 is required for normal development of cranial and cardiac neural crest derived structures. AB - Pinch1, an adaptor protein composed of 5 LIM domains, has been suggested to play an important role in multiple cellular processes. We found that Pinch1 is highly expressed in neural crest cells and their derivatives. To examine the requirement for Pinch1 in neural crest development, we generated neural crest conditional Pinch1 knockout mice using the Wnt1-Cre/loxP system. Neural crest conditional Pinch1 mutant embryos die perinatally from severe cardiovascular defects with an unusual aneurysmal common arterial trunk. Pinch1 mutants also exhibit multiple deficiencies in cranial neural crest-derived structures. Fate mapping demonstrated that initial migration of neural crest cells to the pharyngeal arch region occurs normally in the mutant embryos. However, in the cardiac outflow tract of mutants, neural crest cells exhibited hyperplasia and failed to differentiate into smooth muscle. Markedly increased apoptosis is observed in outflow tract cushions of mutants between embryonic days 11.5 and 13.5, likely contributing to the observed defects in cushion/valve remodeling and ventricular septation. Expression of transforming growth factor-beta(2), which plays a crucial role in outflow tract development, was decreased or absent in the outflow tract of the mutants. The decrease in transforming growth factor-beta(2) expression preceded neural crest cell death. Together, our results demonstrate that Pinch1 plays an essential role in neural crest development, perhaps in part through transforming growth factor-beta signaling. PMID- 17272816 TI - Reversible glutathiolation of caspase-3 by glutaredoxin as a novel redox signaling mechanism in tumor necrosis factor-alpha-induced cell death. PMID- 17272817 TI - Endothelial cell protein C receptor: role beyond endothelium? PMID- 17272818 TI - Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. AB - Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the first of a 2-part review focused on phenotypic heterogeneity of blood vessel endothelium. This review provides an historical perspective of our understanding of endothelial heterogeneity, discusses the scope of phenotypic diversity across the vascular tree, and addresses proximate and evolutionary mechanisms of endothelial cell heterogeneity. The overall goal is to underscore the importance of phenotypic heterogeneity as a core property of the endothelium. PMID- 17272819 TI - Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. AB - Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the second of a 2-part review on the phenotypic heterogeneity of blood vessel endothelial cells. The first part discusses the scope, the underlying mechanisms, and the diagnostic and therapeutic implications of phenotypic heterogeneity. Here, these principles are applied to an understanding of organ-specific phenotypes in representative vascular beds including arteries and veins, heart, lung, liver, and kidney. The goal is to underscore the importance of site specific properties of the endothelium in mediating homeostasis and focal vascular pathology, while at the same time emphasizing the value of approaching the endothelium as an integrated system. PMID- 17272820 TI - Antibody and complement in transplant vasculopathy. AB - Advances in immunosuppression have decreased the incidence of acute rejection, but the development of vasculopathy in the coronary arteries of transplants continues to limit the survival of cardiac allografts. Transplant vasculopathy has also been referred to as accelerated graft arteriosclerosis because it has features of arteriosclerosis, but it is limited to the graft and develops over a period of months to years. Although the pathological features of transplant vasculopathy are well defined, the causative mechanisms are not completely understood. This review focuses on the mechanisms by which antibody and complement can cause or contribute to coronary vasculopathy in cardiac transplants. Antibodies and complement can have independent effects, but the combination of antibodies and complement with inflammatory cells has greater pathogenic potential for the endothelial and smooth muscle cells of the coronary arteries. For example, stimulation through receptors for IgG or complement split products can activate macrophages, but stimulation through combinations of these receptors generates synergistic results. Together, antibodies and complement efficiently integrate the activation of endothelial cells, platelets, and macrophages, which are 3 of the primary components in the pathogenesis of transplant vasculopathy. Recent findings indicate that antibodies and complement produced within the transplant may contribute to vascular pathology in some transplants. Acute rejection caused by antibodies and complement has been treated by combinations of plasmapheresis, intravenous gamma-globulin and monoclonal antibodies to CD20 on B lymphocytes. The effect of these treatment modalities on the development of coronary vasculopathy is unknown. PMID- 17272821 TI - Repeated allergen inhalation induces cytoskeletal remodeling in smooth muscle from rat bronchioles. AB - Airway hyperresponsiveness (AHR) is associated with airway wall structural remodeling and alterations in airway smooth muscle (ASM) function. Previously, in bronchioles from Brown Norway rats challenged by repeated ovalbumin (OVA) inhalation, we have reported increased force generation and depletion of smooth muscle contractile proteins. Here, we investigated if cytoskeletal changes in smooth muscle could account for this paradox. Sensitized rats (n = 5/group) were repeatedly challenged with OVA or saline, and the lungs were removed 24 h after the last challenge. Levels of globular (G) and filamentous (F) actin in bronchioles were determined by DNase I inhibition and contraction assessed in intact small bronchioles using a myograph. DNase I inhibition assays showed that G-actin monomers were more abundant ( approximately 1F:2G) in extracts from resting small bronchioles from OVA- or saline-challenged animals. However, while contractile protein levels in bronchioles were reduced by OVA (P < 0.05), the proportion of F:G actin was 1.8-fold greater compared with saline challenge (P < 0.05). Consistent with induction of F-actin after OVA challenge, increases in maximum tension development to carbachol or KCl in small bronchioles from OVA challenged animals were abrogated (P < 0.01) by actin cytoskeleton disruption with 0.5 microM latrunculin A. Cytoskeletal stabilization of F-actin with 0.1 microM jasplakinolide potentiated maximum contractions to carbachol or KCl (P < 0.05) in bronchioles from OVA- but not saline-treated rats. We conclude that alterations in the composition and/or arrangement of the contractile apparatus after OVA exposure confer enhanced contractile responses, possibly as a result of increased F-actin content. Such a mechanism may have relevance for AHR found in allergic asthma. PMID- 17272822 TI - VCP/p97 AAA-ATPase does not interact with the endogenous wild-type cystic fibrosis transmembrane conductance regulator. AB - The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is defective in cystic fibrosis. The most common mutation, DeltaF508 CFTR, is retained in the endoplasmic reticulum, retrotranslocated into the cytosol, and degraded by the proteasome. In a proteomics screen to identify DeltaF508 CFTR interacting proteins, we found that valosin-containing protein (VCP)/p97, a Type II AAA ATPase that is a component of the retrotranslocation machinery, binds DeltaF508 CFTR, and this interaction is stabilized by proteasomal inhibition. Since wild-type (WT) CFTR has been reported to be inefficiently processed during biogenesis with as much as 75% of the newly synthesized protein degraded by the proteasome, we examined the VCP interaction in Calu-3, T-84, and 16HBE, three epithelial cell lines that endogenously express WT CFTR. The results indicate that when WT CFTR processing is efficient, as demonstrated in Calu-3 cells, VCP does not interact. Interestingly, overexpression of recombinant WT CFTR in Calu-3 cells results in inefficient processing and VCP interaction, demonstrating that CFTR processing efficiency and the VCP interaction are tightly coupled. Furthermore, induction of ER stress and activation of the unfolded protein response result in inefficient processing of WT CFTR in Calu-3 cells and promote the WT CFTR-VCP interaction. The results support the hypothesis that components of the retrotranslocation machinery such as VCP do not interact with CFTR in epithelial cells that endogenously express WT CFTR, since under normal conditions the processing of the WT protein is efficient. PMID- 17272823 TI - Regulation of Bcl-xL expression in lung vascular smooth muscle. AB - Pulmonary hypertension is characterized by thickened pulmonary arterial walls due to increased number of pulmonary artery smooth muscle cells (PASMC). Apoptosis of PASMC may play an important role in regulating the PASMC number and may be useful for reducing pulmonary vascular thickening. The present study examined the regulation of an anti-apoptotic protein Bcl-x(L). Bcl-x(L) expression was found to be increased in the pulmonary artery of chronic hypoxia-treated rats with pulmonary vascular remodeling. Adenovirus-mediated gene transfer of Bcl-x(L) indeed showed that this protein has anti-apoptotic activities in PASMC. Treatment of remodeled pulmonary artery with sodium nitroprusside (SNP) reduced Bcl-x(L) expression by targeting the bcl-x(L) promoter. The bcl-x(L) promoter contains two GATA elements, and SNP decreases the GATA-4 DNA-binding activity. Overexpression of GATA-4 attenuated the SNP-mediated suppression of Bcl-x(L) expression, providing direct evidence for the role of GATA-4 in Bcl-x(L) gene transcription. We established that SNP targets the 250 proximal region of the gata4 promoter and suppresses its gene transcription. Thus, inducers of pulmonary hypertension enhance anti-apoptotic Bcl-x(L) gene transcription, which can be suppressed by targeting gata4 gene transcription. PMID- 17272824 TI - Parthenolide inhibits IkappaB kinase, NF-kappaB activation, and inflammatory response in cystic fibrosis cells and mice. AB - Cystic fibrosis (CF) is characterized by prolonged and excessive inflammatory responses in the lung and increased activation of NF-kappaB. Parthenolide is a sesquiterpene lactone derived from the plant feverfew, which has been used in folk medicine for anti-inflammatory activity. Several studies suggest that this compound inhibits the NF-kappaB pathway, but the exact site is controversial. We hypothesized that parthenolide might ameliorate the excessive inflammatory response in CF models by inhibiting activation of NF-kappaB. This was tested in vitro, using two pairs of cell lines with defective versus normal CF transmembrane conductance regulator (CFTR) (antisense/sense transfected 16 HBE and IB-3/S9), and in vivo, using CFTR-knockout (KO) mice. All cell lines were pretreated with parthenolide and then stimulated with IL-1beta and/or TNF. Parthenolide significantly inhibited IL-8 secretion induced by these cytokines and prevented NF-kappaB activation, IkappaBalpha degradation, and IkappaB Kinase complex activity. CFTR-KO and wild-type mice were pretreated with parthenolide or vehicle alone then challenged intratracheally with LPS. Bronchoalveolar lavage was performed 3, 6, and 8 h later. Parthenolide pretreatment inhibited PMN influx as well as cytokine and chemokine production. This was also associated with inhibition of IkappaBalpha degradation and NF-kappaB activation. We thus conclude that parthenolide inhibits IkappaB kinase, resulting in stabilization of cytoplasmic IkappaBalpha, which in turn leads to inhibition of NF-kappaB translocation and attenuation of subsequent inflammatory responses. IkappaB kinase may be a good target, and parthenolide and/or feverfew might be promising treatments for the excessive inflammation in CF. PMID- 17272826 TI - Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. AB - Fine particles (0.1-2.5 microm in diameter) may cause increased pulmonary morbidity and mortality. We demonstrate with a cell culture model of the human epithelial airway wall that dendritic cells extend processes between epithelial cells through the tight junctions to collect particles in the "luminal space" and to transport them through cytoplasmic processes between epithelial cells across the epithelium or to transmigrate through the epithelium to take up particles on the epithelial surface. Furthermore, dendritic cells interacted with particle loaded macrophages on top of the epithelium and with other dendritic cells within or beneath the epithelium to take over particles. By comparing the cellular interplay of dendritic cells and macrophages across epithelial monolayers of different transepithelial electrical resistance, we found that more dendritic cells were involved in particle uptake in A549 cultures showing a low transepithelial electrical resistance compared with dendritic cells in16HBE14o cultures showing a high transepithelial electrical resistance 10 min (23.9% versus 9.5%) and 4 h (42.1% versus 14.6%) after particle exposition. In contrast, the macrophages in A549 co-cultures showed a significantly lower involvement in particle uptake compared with 16HBE14o co-cultures 10 min (12.8% versus 42.8%) and 4 h (57.4% versus 82.7%) after particle exposition. Hence we postulate that the epithelial integrity influences the particle uptake by dendritic cells, and that these two cell types collaborate as sentinels against foreign particulate antigen by building a transepithelial interacting cellular network. PMID- 17272825 TI - Concordant modulation of cysteinyl leukotriene receptor expression by IL-4 and IFN-gamma on peripheral immune cells. AB - Arachidonic acid can be metabolized to form a group of compounds known as the cysteinyl leukotrienes (CysLT) that bind to one of two receptors to mediate their actions. On circulating cells, expression of the leukotriene receptors is low, but in inflamed tissue the receptor number is dramatically increased. We hypothesized that the cytokine milieu present during inflammation can increase receptor expression on infiltrating immune cells. Various cell populations were purified from peripheral blood and stimulated in vitro with cytokines characteristic of allergic inflammatory disorders, and CysLT receptor expression was measured using quantitative PCR analysis, Western blot, and flow cytometry. IL-4, but not IL-13, was able to significantly induce mRNA and protein levels for both CysLT receptor 1 and 2 from T cells and B cells. CysLT2 receptor expression was also significantly increased in monocytes and eosinophils after IL-4 stimulation. Surprisingly, CysLT2 receptor expression was increased in monocytes, T cells, and B cells when IFN-gamma was used as the stimulus. Factors involved in eosinophil growth and survival were tested for their ability to alter CysLT receptor expression. These results support the concept that cytokines increase expression of both receptors on lymphocytes and granulocytes, allowing these cells to be more responsive to secreted leukotrienes at sites of inflammation. PMID- 17272827 TI - A simple strategy for mitigating the effect of data variability on the identification of active chemotypes from high-throughput screening data. AB - Among the several goals of a high-throughput screening campaign is the identification of as many active chemotypes as possible for further evaluation. Often, however, the number of concentration response curves (e.g., IC(50)s or K(i)s) that can be collected following a primary screen is limited by practical constraints such as protein supply, screening workload, and so forth. One possible approach to this dilemma is to cluster the hits from the primary screen and sample only a few compounds from each cluster. This introduces the question as to how many compounds must be selected from a cluster to ensure that an active compound is identified, if it exists at all. This article seeks to address this question using a Monte Carlo simulation in which the dependence of the success of sampling is directly linked to screening data variability. Furthermore, the authors demonstrate that the use of replicated compounds in the screening collection can easily assess this variability and provide a priori guidance to the screener and chemist as to the extent of sampling required to maximize chemotype identification during the triage process. The individual steps of the Monte Carlo simulation provide insight into the correspondence between the percentage inhibition and eventual IC(50) curves. PMID- 17272828 TI - NF-kappaB is important for TNF-alpha-induced lipolysis in human adipocytes. AB - Tumor necrosis factor-alpha (TNF-alpha) promotes lipolysis in mammal adipocytes via the mitogen-activated protein kinase (MAPK) family, resulting in reduced expression/function of perilipin (PLIN). The role of another pivotal intracellular messenger activated by TNF-alpha, nuclear factor-kappaB (NF kappaB), has not been recognized. We explored the role of NF-kappaB in TNF-alpha induced lipolysis of human fat cells. Primary cultures of human adipocytes were incubated in the presence of a cell-permeable peptide that inhibits NF-kappaB signaling (WP). Incubation with WP, but not with a biologically inactive peptide (MP), abolished the nuclear translocation of NF-kappaB and effectively abrogated TNF-alpha-induced lipolysis in a concentration-dependent manner. Western blot analysis demonstrated that although TNF-alpha per se reduced mainly PLIN protein expression, TNF-alpha in the presence of WP resulted in a pronounced combined reduction of both hormone-sensitive lipase (HSL) and PLIN protein. The expression of a set of other lipolytic or adipocyte-specific proteins was not affected. The regulation was presumably at the transcriptional level, because mRNA expression for HSL and PLIN was markedly reduced with TNF-alpha in the presence of NF-kappaB inhibition. This was confirmed in gene reporter assays using human PLIN and HSL promoter constructs. We conclude that in the presence of NF-kappaB inhibition, TNF-alpha-mediated lipolysis is reduced, which suggests that NF-kappaB is essential for retained human fat cell lipolysis. PMID- 17272829 TI - Functional LCAT deficiency in human apolipoprotein A-I transgenic, SR-BI knockout mice. AB - Reduction of plasma LCAT activity has been observed in several conditions in which the size of HDL particles is increased; however, the mechanism of this reduction remains elusive. We investigated the plasma activity, mass, and in vivo catabolism of LCAT and its association with HDL particles in human apolipoprotein A-I transgenic, scavenger receptor class B type I knockout (hA-ITg SR-BI-/-) mice. Compared with hA-ITg mice, hA-ITg SR-BI-/- mice had a 4-fold higher total plasma cholesterol concentration, which occurred predominantly in 13-18 nm diameter HDL particles, a significant reduction in plasma esterified cholesterol total cholesterol (EC/TC) ratio, and significantly lower plasma LCAT activity, suggesting a decrease in LCAT protein. However, LCAT protein in plasma, hepatic mRNA for LCAT, and in vivo turnover of 35S-radiolabeled LCAT were similar in both genotypes of mice. HDL from hA-ITg SR-BI-/- mice was enriched in sphingomyelin (SM), relative to phosphatidylcholine, and had less associated [35S]LCAT radiolabel and endogenous LCAT activity compared with HDL from hA-ITg mice. We conclude that the decreased EC/TC ratio in the plasma of hA-ITg SR-BI-/- mice is attributed to a reduction in LCAT reactivity with SM-enriched HDL particles. PMID- 17272830 TI - Detailed characterization of the lipid A fraction from the nonpathogen Acinetobacter radioresistens strain S13. AB - The genus Acinetobacter is composed of ubiquitous, generally nonpathogen environmental bacteria. Interest concerning these microorganisms has increased during the last 30 years, because some strains, belonging to the so-called A. baumannii-A. calcoaceticus complex, have been implicated in some severe pathological states in debilitated and hospitalized patients. The involvement of lipopolysaccharides (LPSs) as virulence factors in infections by Acinetobacter has been proven, and ongoing studies are aimed toward the complete serological characterization of the O-polysaccharides from LPSs isolated in clinical samples. Conversely, no characterization of the lipid A fraction from Acinetobacter strains has been performed. Here, the detailed structure of the lipid A fraction from A. radioresistens S13 is reported for the first time. A. radioresistens strains have never been isolated in cases of infectious disease. Nevertheless, it is known that the lipid A structure, with minor variations, is highly conserved across the genus; thus, structural details acquired from studies of this nonpathogen strain represent a useful basis for further studies of pathogen species. PMID- 17272831 TI - Highly sensitive assay of HMG-CoA reductase activity by LC-ESI-MS/MS. AB - We have developed a new sensitive and specific nonradioisotope assay method to measure the activity of HMG-CoA reductase, the rate-controlling enzyme in the cholesterol biosynthetic pathway. This method was based upon a stable isotope dilution technique by liquid chromatography-tandem mass spectrometry using electrospray ionization in positive mode. Mevalonic acid, the product of HMG-CoA reductase, was converted to mevalonolactone (MVL) in an incubation mixture, extracted by a salting-out procedure, derivatized into the mevalonyl-(2 pyrrolidin-1-yl-ethyl)-amide, and then purified using a disposable silica cartridge. The resulting mevalonylamide was quantified by selected reaction monitoring using the positive electrospray ionization mode. The detection limit of this mevalonylamide was found to be 240 amol (signal-to-noise ratio=3), approximately 833 times more sensitive than that of MVL measured by a conventional radioisotope (RI) method (200 fmol). The variances between sample preparations and between measurements by this method were analyzed by one-way layout and calculated to be 3.2% and 1.8%, respectively. The recovery experiments were performed using incubation mixtures spiked with 0.77-2.31 nmol MVL/mg protein and were validated by a polynomial equation. These results showed that the estimated concentration within a 95% confidence limit was 0.47+/-0.07 nmol/mg protein, which coincided completely with the observed X0 nmol/mg protein with a mean recovery of 94.6%. This method made it possible to measure HMG-CoA reductase activity with a high degree of reproducibility and reliability, and especially with sensitivity superior to that of the conventional RI method. PMID- 17272832 TI - Breast cancer patients' expectations in respect of the physician-patient relationship and treatment management results of a survey of 617 patients. AB - BACKGROUND: The following study was conducted to explore patients' information needs and preferences with a special focus on doctor-patient communication. PATIENTS AND METHODS: A 62-item questionnaire developed by a multidisciplinary team and validated in a phase-I study was given to breast cancer patients via the Internet (homepage) or in a hard copy version. RESULTS: A total of 617 patients responded, 552 on line and 65 via the hard copy questionnaire. The median age of the on-line group was 47 (21-85) and 55 (40-92) in the hard copy group. Sixty five per cent of the patients were treated with the intention of achieving a cure and 35% of the patients had metastatic disease. The median length of the consultation communicating the information 'You have breast cancer' was 15 min (0 300). The most effective and patient-relevant source of information about the disease and the treatment options was consultation with the physician (84%). When asked to suggest areas for improvement, patients' most common answers were: more complementary therapies should be offered by the physician (54%); physicians should take more time to explain things (51%); and cooperation between the physicians involved in the patient's care should be improved (39%). The questions most relevant to patients were: 'Am I getting the right therapy?' (89%); 'How many patients with my condition does my doctor treat?' (46%) and 'Can I be enrolled into a trial?' (46%). An independent second opinion centre was desired by 94% of the respondents but only 20% knew of any such resource. CONCLUSIONS: This study underlines the need to give patients with breast cancer the full details on treatment options and cancer management. The results provide a suitable basis for a broader interdisciplinary discussion of the patient physician relationship and should be useful in generating hypotheses for subsequent prospective studies. PMID- 17272834 TI - A generic method for the production of recombinant proteins in Escherichia coli using a dual hexahistidine-maltose-binding protein affinity tag. AB - A generic protocol that utilizes a dual hexahistidine-maltose-binding protein (His6-MBP) affinity tag has been developed for the production of recombinant proteins in Escherichia coli. The MBP moiety improves the yield and enhances the solubility of the passenger protein while the His-tag facilitates its purification. The fusion protein (His6-MBP-passenger) is purified by immobilized metal affinity chromatography (IMAC) on nickel-nitrilotriacetic acid (Ni-NTA) resin and then cleaved in vitro with His6-tobacco etch virus protease to separate the His6-MBP from the passenger protein. In the final step, the unwanted byproducts of the digest are absorbed by a second round of IMAC, leaving nothing but the pure passenger protein in the flow-through fraction. Endogenous proteins that bind to the Ni-NTA resin during the first IMAC step also do so during the second round of IMAC. Hence, the application of two successive IMAC steps, rather than just one, is the key to obtaining crystallization-grade protein with a single affinity technique. PMID- 17272833 TI - Methyl recycling activities are co-ordinately regulated during plant development. AB - A large number of compounds including lignin, phospholipids, pectin, DNA, mRNA, and proteins require methyl groups for their functionality. A detailed study of the expression and activities of two enzymes, adenosine kinase (ADK) and S adenosylhomocysteine hydrolase (SAHH), which are both required for the maintenance and recycling of S-adenosylmethionine-dependent methylation in plants, was carried out. The abundance and tissue localization of ADK and SAHH transcripts and protein were monitored along with their enzyme activities in leaves, stems, buds, siliques, and roots of Arabidopsis. In all but roots and seed coats, the transcript abundance of ADK and SAHH fluctuated co-ordinately, matching changes in their protein and enzyme activities. To evaluate whether this expression pattern was associated with methyl recycling, the protein content and distribution of S-adenosylmethionine synthetase and phosphoethanolamine N methyltransferase, a key methyltransferase involved in phospholipid synthesis, were investigated. These were found to accumulate in a pattern similar to ADK and SAHH. ADK and SAHH protein and transcript amounts were shown to fluctuate similarly in tissues accumulating lignin. Additionally, the amounts of ADK and SAHH mRNAs were also found at high levels in inflorescence meristems likely to support their higher rates of cell division. Thus, the results point to a co ordinated and probably transcriptional regulation of these genes in most organs of Arabidopsis; SAHH abundance is distinctly higher in seeds and roots which suggests it may have a non-methyl-related role in these organs. PMID- 17272836 TI - Baculoviral expression of an integral membrane protein for structural studies. AB - The baculovirus system has proven successful for the expression of integral membrane proteins for structural studies. A recombinant baculovirus, in which the gene of interest is placed under the control of the late-stage polyhedrin promoter, serves as the starting point for viral expansion and protein expression studies. Using large-scale insect cell culture techniques together with a filter binding assay for protein function, the conditions of expression, purification, and solubilization can be optimized. As applied to the glutamate receptor ion channel subunit GluR2, this approach yields milligram quantities of pure, active protein, which have been used for single-particle electron microscopic analysis of the receptor structure. Detergent exchange protocols are also discussed, as a prerequisite for two-dimensional crystallization trials. PMID- 17272835 TI - Cloning, production, and purification of proteins for a medium-scale structural genomics project. AB - The South-Paris Yeast Structural Genomics Pilot Project (http://www.genomics.eu.org) aims at systematically expressing, purifying, and determining the three-dimensional structures of Saccharomyces cerevisiae proteins. We have already cloned 240 yeast open reading frames in the Escherichia coli pET system. Eighty-two percent of the targets can be expressed in E. coli, and 61% yield soluble protein. We have currently purified 58 proteins. Twelve X ray structures have been solved, six are in progress, and six other proteins gave crystals. In this chapter, we present the general experimental flowchart applied for this project. One of the main difficulties encountered in this pilot project was the low solubility of a great number of target proteins. We have developed parallel strategies to recover these proteins from inclusion bodies, including refolding, coexpression with chaperones, and an in vitro expression system. A limited proteolysis protocol, developed to localize flexible regions in proteins that could hinder crystallization, is also described. PMID- 17272837 TI - Protein engineering. AB - This chapter focuses on protein engineering strategies that aim to increase the chances of obtaining crystals suitable for X-ray diffraction. The chapter is divided into three main parts: one dealing with protein engineering through a bioinformatics approach, the second focusing on DNA modifications via random mutagenesis, and the third describing a nonexhaustive number of in vitro modifications based on site-directed mutagenesis. PMID- 17272838 TI - Production of selenomethionyl proteins in prokaryotic and eukaryotic expression systems. AB - The use of selenomethionine as a phasing tool was first reported in 1990. Engineering of selenomethionyl proteins for structure determination is now routine. In fact, selenium is by far the most commonly used anomalous scatterer for multiwavelength anomalous diffraction studies. The past few years have seen new developments, which demonstrated the feasibility of expressing selenomethionyl protein in eukaryotic systems. In this chapter, the different methods available for producing selenomethionine-labeled proteins in bacteria, as well as in yeast and mammalian cells will be presented, along with tips for purifying and crystallizing selenomethionyl proteins. PMID- 17272839 TI - How to use dynamic light scattering to improve the likelihood of growing macromolecular crystals. AB - Dynamic light scattering (DLS) has become one of the most useful diagnostic tools for crystallization. The main purpose of using DLS in crystal screening is to help the investigator understand the size distribution, stability, and aggregation state of macromolecules in solution. It can also be used to understand how experimental variables influence aggregation. With commercially available instruments, DLS is easy to perform, and most of the sample is recoverable. Most usefully, the homogeneity or monodispersity of a sample, as measured by DLS, can be predictive of crystallizability. PMID- 17272840 TI - Screening and optimization methods for nonautomated crystallization laboratories. AB - Crystallization of biological macromolecules is becoming increasingly automated. However, for various reasons, many laboratories still perform at least some aspects of the work manually. A typical crystallization project entails two distinct steps: screening and optimization. The aim of the initial phase is to screen the many parameters affecting crystallization, and as broadly as possible. If any promising conditions are found, these are optimized with other protocols. This chapter describes procedures for manual screening by the vapor diffusion and microbatch methods in 96- and 24-well plate formats. For optimization, several protocols are presented, including grid and additive screens, seeding, and manipulation of the drop kinetics. The scoring of crystallization results and methods for distinguishing protein and salt crystals are also discussed in this chapter. PMID- 17272841 TI - Improving marginal crystals. AB - The physical chemistry of crystal growth can help to identify directions in which to look for improved crystal properties. In this chapter, we summarize how crystal growth depends on parameters that can be controlled experimentally, and relate them to the tools available for optimizing a particular crystal form for crystal shape, volume, and diffraction quality. Our purpose is to sketch the conceptual basis of optimization and to provide sample protocols derived from those foundations. We hope to assist even those who chose not to use systematic methods by enabling them to carry out rudimentary optimization searches armed with a better understanding of how the underlying physical chemistry operates. PMID- 17272842 TI - Optimization techniques for automation and high throughput. AB - The main effort in the area of crystallization for structural genomics is currently being invested in automation of high-throughput screening procedures to identify potential crystallization conditions. However, screening in itself, even in massive quantities, is not enough; it has to be complemented by an equally important procedure in crystal production, namely crystal optimization. This chapter describes optimization methods for turning low-quality crystals into useful diffracting ones and presents practical ways of automating such methods and adapting them to high throughput. The methods enable the control of the crystallization environment as the trial takes place. They include the use of oils, gels, and the uncoupling of the nucleation and growth phases of crystallization. PMID- 17272843 TI - Three-dimensional crystallization of membrane proteins. AB - Although the examination of the protein data bank reveals an important backlog in the number of three-dimensional structures of membrane proteins, several recent successes are serving as preludes to what will become a very prosperous decade in this field. Systematic investigations of various factors affecting the stability of membrane proteins, as well as their potential to crystallize three dimensionally, have paved the way for such achievements. The importance of the role of detergents both at the level of purification and crystallization is now well established. In addition, the recognition of the protein-detergent complex as the entity to crystallize, as well as the understanding of its physical chemical properties and discovery of factors affecting these, have permitted the design of better crystallization strategies. As a consequence of the various efforts in the field, new crystallization methods for membrane proteins are being implemented. These have already been successful and are expected to contribute significantly to the future successes. This chapter will review some basic principles in membrane protein crystallization and give an overview of the current state of the art in the field. Some practical guidelines to help the novice approach the problem of membrane protein crystallization from the initial step of protein purification to crystallogenesis will also be given. PMID- 17272844 TI - Crystallization of protein-DNA complexes. AB - Determining the crystal structure of a protein-DNA complex can provide a wealth of information regarding protein function and mechanism. The foundation for all successful X-ray structure determination is the ability to produce diffraction quality crystals. Crystallization of protein-DNA complexes often presents unique challenges because of the additional parameters involved. This chapter will outline many of those challenges, including choice of DNA and formation of a stable protein-DNA complex and provide guidance in preparing for crystallization experiments. Additionally, techniques for oligonucleotide purification, sample preparation, and crystallization methods are provided. Careful thought and initial analysis of the protein-DNA complex prior to crystallization experiments followed by optimization of crystallization parameters can greatly increase the likelihood of producing well-diffracting crystals. PMID- 17272845 TI - Preparation and crystallization of RNA. AB - The field of RNA structure has exploded in recent years, in part owing to advances in crystallography of RNA molecules. This phenomenon can largely be attributed to the development of three modern methods: (1) large-scale in vitro RNA synthesis, (2) cryocrystallography, and (3) high-intensity synchrotron beamlines. Milligram quantities of RNA can be routinely synthesized using either chemical or enzymatic syntheses, making it feasible to carry out routine crystallization experiments on RNA. This has allowed crystals of RNA to be readily obtained. Generally, RNA crystals tend to be susceptible to radiation damage and to diffract X-rays more weakly than their protein counterparts. However, cryocrystallography and the high-intensity X-ray sources have overcome many of the difficulties involved in solving crystal structures of RNA. As a result of these advances, we now have a database of RNA structures that span from simple duplexes and hairpins to complex ribozymes and ribosomes. The protocols presented here describe methods to synthesize, purify, crystallize, and derivatize RNA for use in crystallographic studies. PMID- 17272846 TI - Crystallization of RNA-protein complexes. AB - RNA-binding proteins play crucial roles in many biological processes, such as transcription, pre-mRNA splicing, nuclear-cytoplasmic transport of RNA, and translation of mRNA. Specific RNA-protein interactions are key to the correct assembly of ribonucleoprotein complexes and their biological functions. To date, more than 100 unique RNA-protein crystals have been prepared and there are more than 300 entries of RNA-protein complex structures in the Protein Data Bank. This chapter focuses on methods of RNA-protein complex crystallization discussed in six sections: determination of protein-binding sites in RNA, preparation of RNA, preparation of protein, annealing of RNA, reconstitution of RNA-protein complex, and searching crystallization conditions. PMID- 17272847 TI - Plasma membrane calcium pump activity in rat pancreatic islets: an accurate method to measure its calcium-dependent modulation. AB - The aim of this study was to quantify the glucose modulation of the plasma membrane calcium pump (PMCA) function in rat pancreatic islets. Ca2+-ATPase activity and levels of phosphorylated PMCA intermediates both transiently declined to a minimum in response to stimulation by glucose. Strictly dependent on Ca2+ concentration, this inhibitory effect was fully expressed at physiological concentrations of the cation (less than 0.5 muM), then progressively diminished at higher concentrations. These results, together with those previously reported on the effects of insulin secretagogues and blockers on the activity, expression and cellular distribution of the PMCA, support the concept that the PMCA plays a key role in the regulation of Ca2+ signaling and insulin secretion in pancreatic islets. PMID- 17272848 TI - Escherichia coli membrane proton conductance and proton efflux depend on growth pH and are sensitive to osmotic stress. AB - The dependence of Escherichia coli membrane H+ conductance (Gm H+) with a steady state pH in the presence and absence of an external source of energy (glucose) was studied, when cells were grown under anaerobic and aerobic conditions, with an assay pH of 7.0. Energy-dependent H+ efflux by intact cells growing at pH of 4.5-7.5 was also measured. The elevated H+ conductance and lowered H+ flux were shown for cells growing in acidic pH and under anaerobic conditions, when bacteria were fermenting glucose. The atp mutant, which is deprived of the F0F1- adenosine triphosphatase, had less Gm H+ independent of growth conditions. In contrast with wild-type or precursor strain, a remarkable difference in Gm H+ for atp mutant was observed between aerobic and anaerobic conditions; such a difference was significant at pH 4.5. These results could indicate distinguishing pathways determining Gm H+ under anaerobic conditions after the fermentation of glucose at different pH and an input of the F0F1-adenosine triphosphatase in Gm H+. In addition, the effect of osmotic stress was demonstrated with grown cells. Gm H+ and H+ efflux both were increased after hyperosmotic stress at pH 7.5, and these changes were inhibited by N,N?'-dicyclohexylcarbodiimide, whereas these changes were lower in atp mutant. A role of the F0F1-adenosine triphosphatase in osmo-sensitivity of bacteria was confirmed under fermentative conditions. PMID- 17272849 TI - Hydrodynamics and cell volume oscillations in the pollen tube apical region are integral components of the biomechanics of Nicotiana tabacum pollen tube growth. AB - Pollen tube growth is localized at the apex and displays oscillatory dynamics. It is thought that a balance between intracellular turgor pressure (hydrostatic pressure, reflected by the cell volume) and cell wall loosening is a critical factor driving pollen tube growth. We previously demonstrated that water flows freely into and out of the pollen tube apical region dependent on the extracellular osmotic potential, that cell volume changes reflect changes in the intracellular pressure, and that cell volume changes differentially induce increases or decreases in specific phospholipid signals. This article shows that manipulation of the extracellular osmotic potential rapidly induces modulations in pollen tube growth rate frequencies, demonstrating that changes in the intracellular pressure are sufficient to reset the pollen tube growth oscillator. This indicates a direct link between intracellular hydrostatic pressure and pollen tube growth. Altering hydrodynamic flow through the pollen tube by replacing extracellular H2O with 2H2O adversely affects both cell volume and growth rate oscillations and induces aberrant morphologies. Normal growth and cell morphology are rescued by replacing 2H2O with H2O. Further studies revealed that the cell volume oscillates in the pollen tube apical region. These cell volume oscillations were not from changes in cell shape at the tip and were detectable up to 30 mum distal to the tip (the longest length measured). Cell volume in the apical region oscillates with the same frequency as growth rate oscillations but surprisingly the cycles are phase-shifted by 180 degrees . Raman microscopy yields evidence that hydrodynamic flow out of the apex may be part of the biomechanics that drive cellular expansion. The combined results suggest that hydrodynamic loading/unloading in the apical region induces cell volume oscillations and has a role in driving cell elongation and pollen tube growth. PMID- 17272850 TI - Theoretical and experimental investigation of calcium-contraction coupling in airway smooth muscle. AB - We investigated theoretically and experimentally the Ca2+-contraction coupling in rat tracheal smooth muscle. [Ca2+]i, isometric contraction and myosin light chain (MLC) phosphorylation were measured in response to 1 mM carbachol. Theoretical modeling consisted in coupling a model of Ca2+-dependent MLC kinase (MLCK) activation with a four-state model of smooth muscle contractile apparatus. Stimulation resulted in a short-time contraction obtained within 1 min, followed by a long-time contraction up to the maximal force obtained in 30 min. ML-7 and Wortmannin (MLCK inhibitors) abolished the contraction. Chelerythrine (PKC inhibitor) did not change the short-time, but reduced the long-time contraction. [Ca2+]i responses of isolated myocytes recorded during the first 90 s consisted in a fast peak, followed by a plateau phase and, in 28% of the cells, superimposed Ca2+ oscillations. MLC phosphorylation was maximal at 5 s and then decreased, whereas isometric contraction followed a Hill-shaped curve. The model properly predicts the time course of MLC phosphorylation and force of the short time response. With oscillating Ca2+ signal, the predicted force does not oscillate. According to the model, the amplitude of the plateau and the frequency of oscillations encode for the amplitude of force, whereas the peak encodes for force velocity. The long-time phase of the contraction, associated with a second increase in MLC phosphorylation, may be explained, at least partially, by MLC phosphatase (MLCP) inhibition, possibly via PKC inhibition. PMID- 17272851 TI - A tryptophan in the bottleneck of the catalytic gorge of an invertebrate acetylcholinesterase confers relative resistance to carbamate and organophosphate inhibitors. AB - Amphioxus, an invertebrate chordate, has two acetylcholinesterases (AChEs): cholinesterase 1 (ChE1) and cholinesterase 2 (ChE2). ChE1 is up to 329-fold more resistant to a variety of carbamate and organophosphate inhibitors, including a number of insecticides, when compared with ChE2. One difference between the two enzymes is at the position homologous to Phe331 in Torpedo AChE. In Torpedo AChE, this residue is a component of the hydrophobic subsite and defines one side of the bottleneck in the catalytic gorge of the enzyme. In ChE1, the homologous residue is Trp353; in ChE2, it is Phe353. We used site-directed mutagenesis to investigate the proposal that the resistance of ChE1 to inhibition by carbamates and organophosphates was due to this difference, creating a ChE1 W353F mutant to widen the bottleneck. The mutation virtually abolishes the difference in sensitivity to the inhibitors. The ChE1 W353F mutant is only 2- to 3-fold more resistant than ChE2 to carbamates and is actually 2.5- to 10-fold more sensitive to inhibition by organophosphates. The differences in resistance are due to different affinities of the enzymes for the inhibitors, not different reactivities. Molecular modeling supports the proposal that the difference in inhibition is due to the width of the bottleneck of the gorge. Our results have implications for insecticide resistance in insects, in particular mosquitoes and aphids. PMID- 17272852 TI - Voltage-dependent calcium channels in young and old human red cells. AB - Presence of subtypes of voltage-dependent Ca channels was investigated in young and old human red cells, employing immunological and flux-kinetics methods. Western blots showed specific reaction toward polyclonal rabbit antibodies raised against a highly conserved residue of alpha1 subunit of high-voltage activated Ca channels (pan alpha1) and against conserved residues of alpha1C and alpha1E subunits. No specific reaction was detected with antibodies against conserved residues of alpha1A, alpha1B, or alpha1D subunits. Only a single band (approx 260 kDa) was revealed on anti-pan alpha1 or anti-alpha1E blots, whereas two bands (200 and 230 kDa) were detected by anti-alpha1C exposure. Blots from old cells always showed diminished band intensity. Channel activity was assessed by studying the effect of voltage-dependent Ca channels blockers under conditions likely to alter the red cell membrane potential, through incubation in media of different composition. In a 150 mM NaCl + 5 mM KCl medium, blockers of L-, R-, and Q-type caused a 15-50% reduction of 45Ca influx into cells, which had the Ca pump inactivated by either exhaustive adenosine triphosphate depletion or presence of vanadate plus substrates. Additionally, some P/Qand N-type blockers also reduced Ca influx to various extents (25-60%). Old cells were generally insensitive to L-type but not to non-L-type blockers. Raising external K to about 70-80 mM reduced by 50-100% inhibition by L-type blockers. Incubation in a gluconate medium containing 150 mM Na+5 mM K practically abolished the action of L-type blockers, but only slightly reducing that by non-L-type. The results clearly demonstrate presence of L- and R-type Ca channels, apparently occurring in different functional states in young and old cells. Other non-L-type channels were also demonstrated only by pharmacological means. A possible physiological role for these channels is discussed. PMID- 17272853 TI - Flow-activated ion channels in vascular endothelium. AB - The ability of vascular endothelial cells (ECs) to respond to fluid mechanical forces associated with blood flow is essential for flow-mediated vasoregulation and arterial wall remodeling. Abnormalities in endothelial responses to flow also play a role in the development of atherosclerosis. Although our understanding of the endothelial signaling pathways stimulated by flow has greatly increased over the past two decades, the mechanisms by which ECs sense flow remain largely unknown. Activation of flow-sensitive ion channels is among the fastest known endothelial responses to flow; therefore, these ion channels have been proposed as candidate flow sensors. This review focuses on: 1) describing the various types of flow-sensitive ion channels that have been reported in ECs, 2) discussing the implications of activation of these ion channels for endothelial function, and 3) proposing candidate mechanisms for activation of flow-sensitive ion channels. PMID- 17272854 TI - Modeling of molecular and cellular mechanisms involved in Ca2+ signal encoding in airway myocytes. AB - In airway myocytes signal transduction via cytosolic calcium plays an important role. In relation with experimental results we review models of basic molecular and cellular mechanisms involved in the signal transduction from the myocyte stimulation to the activation of the contractile apparatus. We concentrate on mechanisms for encoding of input signals into Ca2+ signals and the mechanisms for their decoding. The mechanisms are arranged into a general scheme of cellular signaling, the so-called bow-tie architecture of signaling, in which calcium plays the role of a common media for cellular signals and links the encoding and decoding part. The encoding of calcium signals in airway myocytes is better known and is presented in more detail. In particular, we focus on three recent models taking into account the intracellular calcium handling and ion fluxes through the plasma membrane. The model of membrane conductances was originally proposed for predicting membrane depolarization and voltage-dependent Ca2+ influx triggered by initial cytosolic Ca2+ increase as observed on cholinergic stimulation. Cellular models of intracellular Ca2+ handling were developed to investigate the role of a mixed population of InsP3 receptor isoforms and the cellular environment in the occurrence of Ca2+ oscillations, and the respective role of the sarcoplasmic reticulum, mitochondria, and cytosolic Ca2+-binding proteins in cytosolic Ca2+ clearance. Modeling the mechanisms responsible for the decoding of calcium signals is developed in a lesser extent; however, the most recent theoretical studies are briefly presented in relation with the known experimental results. PMID- 17272855 TI - The Na,K-ATPase receptor complex: its organization and membership. AB - A major difference between the Na,K-ATPase ion pump and other P-type ATPases is its ability to bind cardiotonic steroids such as ouabain. Na,K-ATPase also interacts with many membrane and cytosolic proteins. In addition to their role in Na,K-ATPase regulation, it became apparent that some of the newly identified interactions are capable of organizing the Na,K-ATPase into various signaling complexes. This new function confers a ligand-like effect to cardiotonic steroids on cellular signal transduction. This article reviews these new developments and provides a comparison of Na,K-ATPase-mediated signal transduction with other receptors and ion transporters. PMID- 17272856 TI - The selection of mosaic (MSC) phenotype after passage of cucumber (Cucumis sativus L.) through cell culture - a method to obtain plant mitochondrial mutants. AB - Mosaic (MSC) mutants of cucumber (Cucumis sativus L.) appear after passage through cell cultures. The MSC phenotype shows paternal transmission and is associated with mitochondrial DNA rearrangements. This review describes the origins and phenotypes of independently produced MSC mutants of cucumber, including current knowledge on their mitochondrial DNA rearrangements, and similarities of MSC with other plant mitochondrial mutants. Finally we propose that passage of cucumber through cell culture can be used as a unique and efficient method to generate mitochondrial mutants of a higher plant in a highly homozygous nuclear background. PMID- 17272857 TI - New genetic map of rye composed of PCR-based molecular markers and its alignment with the reference map of the DS2 x RXL10 intercross. AB - A new genetic map of rye, developed by using the 541 x Ot1-3 F2 intercross, consists of 148 marker loci, including 99 RAPDs, 18 SSRs, 14 STSs, 9 SCARs and 7 ISSRs, and spans the distance of 1401.4 cM. To the 7 rye chromosomes, 8 linkage groups were assigned and compared with the reference map of the DS2 x RXL10 F2 intercross by using 24 common markers. The 2 combined maps contain altogether 611 marker loci (70-109 per chromosome) and constitute a substantial source of information useful for further genomic studies in rye. From 21 to 37 RAPD marker loci are distributed randomly along each chromosome length and their total number for all 7 rye chromosomes is 177. This abundance of RAPD marker loci in the rye genetic map can be exploited for development of SCARs in regions containing important genes or QTL. PMID- 17272858 TI - Exploration of genetic diversity among Xinjiang Triticum and Triticum polonicum by AFLP markers. AB - Seventy-two Xinjiang Triticum and Triticum polonicum accessions were subjected to AFLP analyses to discuss the origin of Triticum petropavlovskyi. A total of 91 putative loci were produced by four primer combinations. Among them 56 loci were polymorphic, which is equivalent to 61.53 % of the total number of putative loci. Genetic diversity among 11 T. petropavlovskyi accessions was narrow due to the lowest number (32) of polymorphic loci among the wheat species. Forty four polymorphic loci were found in T. aestivum and T. compactum, whereas the highest polymorphism was observed in T. polonicum. On the basis of the UPGMA clustering and PCO grouping and genetic similarity estimates from the AFLPs, we noted that T. petropavlovskyi was more closely related to the Chinese accessions of T. polonicum than to T. polonicum from other countries. Two accessions of T. aestivum were grouped with T. petropavlovskyi in the UPGMA clustering. Both of them were similar to T. petropavlovskyi in respect of spike structure, i.e. the presence of awn, glume awn and also the presence of leaf pubescence. Six loci, which were commonly absent in Chinese T. polonicum, were also absent in almost all of the T. petropavlovskyi accessions. Findings of this study reduced the probability of an independent allopolyploidization event in the origin of T. petropavlovskyi and indicated a greater degree of gene flow between T. aestivum and T. polonicum leading to T. petropavlovskyi. It is most likely that the P-gene of T. petropavlovskyi hexaploid wheat was introduced from T. polonicum to T. aestivum via a spontaneous introgression or breeding effort. PMID- 17272859 TI - EST-SSR DNA polymorphism in durum wheat (Triticum durum L.) collections. AB - SSRs derived from EST were molecular markers belonging to the transcribed region of the genome. Therefore, any polymorphism detected using EST-SSRs might reflect the better relationship among species or varieties. Using wheat EST-SSR markers, 60 durum wheat (Triticum durum L.) accessions from seven countries were investigated. Twenty-five primer pairs could amplify successfully in the 60 durum wheat accessions, of which tri-nucleotide repeats were the dominant type, and revealed 26 loci on all seven wheat homologous chromosome groups. A total of 87 eSSR alleles were detected, and the number of alleles detected by a single pair of primers ranged from 1 to 11, with an average of 3.3 alleles per locus. Higher numbers of alleles and PIC were identified on the B genome than those on the A genome. PMID- 17272860 TI - Inheritance of resistance to stripe rust in winter wheat cultivars Aquileja and Xian Nong 4. AB - Winter wheat cultivars Aquileja (AQ) and Xian Nong 4(XN) were previously reported to possess durable, quantitative resistance to stripe rust disease. In the present study, AQ, XN and a susceptible wheat cultivar were reciprocally crossed in all 6 combinations. Parents, F1, F2, F3, BCP1 and BCP2 were used to determine quantitative genetic parameters for infection type and disease severity. The results showed that fixable genetic components preponderated in the inheritance of the resistance in AQ and XN for both infection type and disease severity, while the dominant component could be detected in some cases. The resistance was conditioned by oligogenes. Heritability of the resistance ranged from 50 to 79% in most cases. PMID- 17272862 TI - Effect of variants in the ovine skeletal-muscle-specific calpain gene on body weight. AB - The ovine skeletal-muscle-specific calpain gene (p94), which is known also as the n-calpain or calpain 3 gene (CAPN3), was screened with primers. Selection of the PCR primers was based on the ovine cDNA sequence (GenBank accession No. AF087570). After sequence alignment between the ovine and human (AY902237) genes, exon and intron boundaries were determined. Polymorphisms were observed in the intron region for the CAPN31112 and CAPN31213 segments, and the sequences for these segments were submitted to the GenBank (AF309635 and AY102617, respectively). Body weight was recorded at birth, weaning and post-weaning. Calpain 3 genotypes of the CAPN31112 segment were associated with birth weight (P < 0.01), and a dominant gene effect was observed. Breeding group, birth type, and rearing type were significantly associated with weight traits. Allele frequencies were similar in purebred and crossbred animals. PMID- 17272863 TI - Deletion/insertion polymorphism of the prion protein gene (PRNP) in Polish Holstein-Friesian cattle. AB - The aim of the present study was to identify the deletion/insertion polymorphism of the bovine prion protein gene (PRNP) within the promoter sequence (23 bp), intron 1 (12 bp) and 3' untranslated region (14 bp). DNA was isolated from blood of 234 randomly tested Polish Holstein-Friesian cows and from semen of 47 sires used for artificial insemination (AI) in 2004. No statistically significant differences were found in the frequency of genotypes and alleles between cows and breeding bulls in the 3 analysed polymorphic sites within the PRNP gene. Only 3 haplotypes were identified in sires and 4 haplotypes in cows. PMID- 17272861 TI - Animal transgenesis: state of the art and applications. AB - There is a constant expectation for fast improvement of livestock production and human health care products. The advent of DNA recombinant technology and the possibility of gene transfer between organisms of distinct species, or even distinct phylogenic kingdoms, has opened a wide range of possibilities. Nowadays we can produce human insulin in bacteria or human coagulation factors in cattle milk. The recent advances in gene transfer, animal cloning, and assisted reproductive techniques have partly fulfilled the expectation in the field of livestock transgenesis. This paper reviews the recent advances and applications of transgenesis in livestock and their derivative products. At first, the state of art and the techniques that enhance the efficiency of livestock transgenesis are presented. The consequent reduction in the cost and time necessary to reach a final product has enabled the multiplication of transgenic prototypes around the world. We also analyze here some emerging applications of livestock transgenesis in the field of pharmacology, meat and dairy industry, xenotransplantation, and human disease modeling. Finally, some bioethical and commercial concerns raised by the transgenesis applications are discussed. PMID- 17272864 TI - Cytogenetic mapping of DGAT1, PPARA, ADIPOR1 and CREB genes in the pig. AB - In the present study we show FISH localization of 4 porcine BAC clones harbouring potential candidate genes for fatness traits: DGAT1 (SSC4p15), PPARA (SSC5p15), ADIPOR1 (SSC10p13) and CREB (SSC15q24). Until now the CREB and ADIPOR1 genes are considered to be monomorphic, DGAT1 is highly polymorphic, while for the PPARA gene only 1 SNP was identified. Assignment of the studied genes in relation to QTL chromosome regions for meat quality in pig chromosomes SSC4, SSC5, SSC10 and SSC15 is discussed. PMID- 17272866 TI - Carrier status for 3 most frequent CFTR mutations in Polish PCD/KS patients: lack of association with the primary ciliary dyskinesia phenotype. AB - We screened a large group of primary ciliary dyskinesia/Kartagener syndrome (PCD/KS) patients and their siblings (148 patients from 126 unrelated families) for the presence of the CFTR mutations that are most frequently found in the Polish population: the severe F508del and 2,3del21kb, and the mild 3849+10kbC > T. No statistically significant increase in the frequency of these mutations was found in the studied group, as compared with the general population. This is consistent with an earlier observation in another population and indicates that the status of being a carrier of any of these CFTR mutations should not be considered as an important risk factor in PCD/KS pathogenesis. PMID- 17272867 TI - Few associations of candidate genes with nonsyndromic orofacial clefts in the population of Lithuania. AB - Nonsyndromic orofacial clefting (NS-OFC) is a common complex multifactorial trait with a considerable genetic component and a number of candidate genes suggested by various approaches. Twenty biallelic and microsatellite DNA markers in the strong candidate loci TGFA, TGFB3, GABRB3, RARA, and BCL3 were analysed for allelic association with the NS-OFC phenotype in 112 nuclear families (proband + both parents) from Lithuania by using the transmission disequilibrium test (TDT). Associations were found between the TGFA gene marker rs2166975 and nonsyndromic cleft palate only (CPO) phenotype (p = 0.045, df 1) as well as between the D2S292 marker and the cleft lip with or without cleft palate (CL/CP) phenotype in allele wise TDT (P = 0.005, df 9) and genotype-wise TDT (P = 0.021, df 24). A weak association (P = 0.085, df 3) of the BCL3 marker (BCL3 gene) with the risk of CPO was also found. Thus our initial results support the contribution of allelic variation in the TGFA locus to the aetiology of CL/CP in the population of Lithuania but they do not point to TGFA as a major causal gene. Different roles of the TGFA and BCL3 genes in the susceptibility to NS-OFC phenotypes are suggested. PMID- 17272865 TI - Methods of minimal residual disease (MRD) detection in childhood haematological malignancies. AB - The appropriate management of haematological disorders must rely on a precise and long-term monitoring of the patient's response to chemotherapy and radiotherapy. Clinical data are not sufficient and that is why in the last decade it became the most important to improve the knowledge of haematological diseases on the basis of molecular techniques and molecular markers. The presence of residual malignant cells among normal cells is termed minimal residual disease (MRD). Nowadays a great progress has been made in the treatment of malignant diseases and in the development of reliable molecular techniques, which are characterised by high sensitivity (10-3- 10-6) and ability to distinguish between normal and malignant cells at diagnosis and during follow-up. Especially, MRD data based on quantitative analysis (RQ-PCR, RT-RQ-PCR) appear to be crucial for appropriate evaluation of treatment response in many haematological malignancies. Implementation of standardized approaches for MRD assessment into routine molecular diagnostics available in all oncohaematological centres should be regarded nowadays a crucial point in further MRD study development. PMID- 17272869 TI - A 9p13-->p24 duplication coupled with a whole 22q translocation onto 9p24. AB - We report on a 3-year-old girl with a typical 9p trisomy syndrome, whose 45 chromosome karyotype includes a 9p+. As assessed by G, C and Ag-NOR bands, the rearranged chromosome resulted from a 9p13-->p24 direct duplication coupled with a translocation of the whole 22q onto 9pter, had heterochromatin at the junction site, lacked both nucleolar organizing regions (NORs) and centromere dots at the unconstricted fusion point, and was present in all metaphases scored. FISH results: a 9p subtelomere probe gave a diminished signal on the 9p+ precisely at the duplication junction 9p24::9p13, but no labeling was observed at the 9;22 translocation site; a pancentromeric alphoid probe labeled all centromeres, and gave a distinct signal at the 9pter;22cen junction. Hence, her karyotype was 45,XX,rea(9;22)(9qter-->9p24::9p13-->9p24::22p10-->22qter).ish rea(9;22) (9psubtel+dim,pancen+). Parental chromosomes were normal. The distinctiveness of the present centromere-telomere fusion rests on the coupling of an intrachromosomal distal duplication with a whole-arm translocation including alphoid DNA onto the duplicated segment. The centromeric inertia of the residual alphoid DNA in the present case compares with the variable functional status of the chromosome 22 centromere in true heterodicentrics involving such a chromosome. PMID- 17272868 TI - De novo complex chromosomal rearrangement of 46, XY, t (3; 16; 8) (p26; q13; q21.2) in a non-obstructive azoospermic male. AB - Complex Chromosomal Rearrangements (CCRs) are rare structural abnormalities that are usually associated with infertility or subfertility in male carriers. We described clinical and chromosomal features of a non-obstructive azoospermic male that has been referred for infertility. Cytogenetic analysis showed three chromosomes, i.e. 3, 8 and 16, which have been involved and caused spermatogenesis failure. PMID- 17272870 TI - [Osteoporosis and oral biology]. AB - Estrogen deficiency in post-menopausal osteoporosis not only causes decreased bone mass in mandibular bone, but also affect cartilaginous ossification in mandibular condyle. Although the mechanisms of action are not entirely clear, estrogen is thought to promote the programmed cell death of osteoclasts and hence reduce their period of activity. Treatment with estrogen or some agents prevent bone loss in alveolar bone through blocking production of cytokines in osteoblasts and promoting osteoclast apoptosis. It's necessary to address basic principles and current concepts in bone remodeling, mediators of bone resorption and their clinical relevance. PMID- 17272871 TI - [Oral osteoporosis: a review and its dental implications]. AB - In post-menopausal osteoporosis, lack of estrogen will affect the remodeling of the bone tissue in such a way that, in most patients with periodontitis, the amount of bone resorbed exceeds that being formed, resulting in net bone loss. Osteoporosis can be treated by a variety of methods, the hormone replacement therapy (HRT), the selective estrogen receptor modulators (SERM) and the bisphosphonates. The HRT or bisphosphonates treatments improve the clinical outcome of periodontal disease and may be an adjunctive treatment to preserve periodontal bone mass. This paper reviews the current evidence on the mechanism of periodontal breakdown after menopause and the benefit to oral health by treatments for osteoporosis. PMID- 17272872 TI - [Structure of jaw bone]. AB - The jaw bone is put in a special environmental condition because it receives not only external force through a masticatory muscle, but occlusal force directly from the teeth. Therefore, the morphology and internal structure of the jaw bone is strongly reflected by the erupted condition of the teeth. In the edentulous jaw bone, the number and thickness of the trabecular bones is reduced as well as decrease of its size. This tendency is quite resemble to the morphological change of osteoporosis. Based on the facts mentioned above, it is suggested that the loss of the teeth induces the fragility of the jaw bone. Therefore, maintenance of a healthy tooth is very important to keep the normal morphology of the jaw bone. PMID- 17272873 TI - [Oral bacteria and periodontitis, with special reference to innate immune system in oral mucosa]. AB - Innate immune system is an ubiquitous system from insects to human and responsible for initial host defense against invasive pathogens, where pathogen associated molecular patterns (PAMPs) are recognized by the pattern recognition molecules of hosts. Representative human receptors for PAMPs are nine Toll-like receptors (TLRs) and intracellular NOD molecules which recognize peptidoglycans of bacterial cell-walls. Oral epithelial cells express various TLRs and NODs so far examined, and these cells in normal condition produce antibacterial factors, but not proinflammatory factors, in response to various PAMPs to prevent bacterial invasion without excessive inflammatory responses. PMID- 17272874 TI - [Oral Biofilms and bone resorption]. AB - A lot of oral diseases, including marginal periodontitis, are infectious diseases that caused by the oral biofilm-forming bacteria for example dental biofilm (dental plaque). The oral biofilm is paid to attention as a risk factor of the systemic disease such as metabolic syndrome, osteoporosis, aspiration pneumonia, diabetics, and the infective endocarditises. It had been shown that 500 bacterial species inhabited with symbiosis and antagonization within the oral biofilm and communication among bacteria is essential for initial colonization and subsequent biofilm formation on human teeth and oral mucosa. The feature and the realities of the biofilm to cause the bone absorption were outlined in this manuscript and speculated how the biofilm-forming bacteria approach to the alveolar bone, although it was difficult to clarify the whole contents of human oral biofilm that presented a various aspect. PMID- 17272875 TI - [Diabetes and oral osteoporosis]. AB - Severe marginal periodontitis often coexists with diabetes and is considered to be the sixth complication of the disease. Several factors associated with diabetes have been shown to be related to the development and deterioration of diabetic periodontitis, i.e., glycated hemoglobin (HbA(1C)), advanced glycation endproducts (AGEs), C-reactive protein (CRP), and glucose tolerance, as well as inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. A periodontal pathogen, Porphyromonas gingivalis with the type II fimbria gene, is also considered to be a related infectious factor. Among them, AGEs seem to be closely associated with the periodontitis deterioration seen in diabetic subjects. Osteoporosis and diabetes are also tightly related, and AGEs have been reported to accelerate the progression of osteoporosis. Collectively, AGEs are a critical diabetic factor to deteriorate oral osteoporosis. PMID- 17272876 TI - [Analysis of alveolar bone]. AB - Several techniques such as intra-oral dental radiographs, dental panoramic radiographs, computed tomography and dual energy x-ray absorptiometry have been used to evaluate the effects of oral diseases such as periodontal disease and systemic diseases such as osteoporosis on quantity and quality of alveolar bone of the jaws. Advanced imaging such as magnetic resonance imaging might also be applied to evaluate them in the future. However, the analysis and evaluation of alveolar bone should be carefully performed in consideration of some limitations included in each technique. PMID- 17272877 TI - [Periostin function in the periodontal ligament and the periosteum]. AB - The periodontal ligament in teeth and the periosteum in bone show the similarity in tissues that consist of the strong collageous connective tissues to moderate or transmit the mechanical stress. Another similarity is the high mechanosensitive response, by which the periodontal ligament and the periosteum are remodeled to tolerate the stress. Here we report about periostin, which is an extracellular matrix protein specifically expressed in the periodontal ligament and the periosteum of tooth and bone tissues. We suggest that periostin contributes to a fusion of osteobioscience and biodentistry. PMID- 17272878 TI - [Mechanisms of alveolar bone remodeling]. AB - The maintenance of bone is achieved by a fine balance between bone formation and bone resorption. The differentiation and activation of osteoclasts are tightly regulated by osteoblasts. Osteoblasts express at least two cytokines essential for osteoclast differentiation; they are receptor activator of NF-kappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF). On the other hand, differentiation of osteoblasts is regulated by the transcription factors Runx2 and Osterix. The recent progress of genetic experiments has revealed that osteoclasts also regulate the differentiation of osteblasts in vivo. This review describes the recent studies on the communication between osteoblasts and osteoclasts in the process of bone remodeling. PMID- 17272879 TI - [Fluoride and bone metabolism]. AB - Fluoride (F) is an essential trace element which is involved in the skeletal systems of teeth and bone. F increases proliferation of osteoblastic cells and stimulates bone formation. F inhibits acid phosphatase activity in osteoblastic cells and induces an increases in tyrosin phosphorylated protein, leading to cell proliferation. Also, the activation of G protein by F is important in the cellular mechanism of F action in osteoblastic cells. F also has inhibitory effects on osteoclastic bone resorption. The oral administration of F solution has stimulatory effects on bone formation in various animal models. Moreover, the intake of F with comparatively low doses may have beneficial effects in the development of bone mineral density and fracture in human. PMID- 17272880 TI - [Smoking and periodontal disease]. AB - Over the past 20 years, numerous investigations have demonstrated epidemiologically and biologically that smoking is one of the most significant risk factors with respect to the development and progression of periodontal disease. In terms of the mechanism via which smoking influences periodontitis progression, various factors contribute to the deleterious periodontal effects of smoking, including alteration of both microbial and host response factors. Furthermore, since it is well known that smoking is also a risk factor of osteoporosis, the combination of smoking with osteoporosis further enhances the risk of periodontal disease. Recent investigations reported that passive smoking exposure may be a risk factor of periodontal disease and may stimulate inflammatory responses of periodontal tissue. PMID- 17272881 TI - [Relationship between bone metabolism and adipogenesis]. AB - Clinically, fatty marrow, accumulation of adipocytes in bone marrow, is often observed in the patients who manifest bone diseases such as osteoporosis. Since adipocytes and osteoblasts are differentiated from mesenchymal stem cells, it would be clinically and biologically important to understand regulatory mechanisms of the balance between adipogenesis and osteoblastogenesis. Recently, experimental findings indicated the involvement of adipokines including leptin and adiponectin in bone metabolisms. Thus, adipocytes appear to play a role in regulation of bone metabolisms. PMID- 17272882 TI - [Bisphosphonates and osteonecrosis of the jaws]. AB - The osteonecrosis of the jaws (ONJ) has been reported occasionally in cancer patients treated with radiotherapy and chemotherapy. However, bisphosphonate (BP) associated ONJ in patients with cancer such as multiple myeloma, breast cancer and prostate cancer mainly administered with intravenous BPs has been first reported in 2003. Since then, many cases over 2,500 are accumulating worldwide. Since BPs are often used for osteoporosis, cancer-associated hypercalcemia and osteolytic bone metastasis, it is speculated that ONJ cases will increase in Japan where a small number of them were reported until now. Most of ONJ in cancer patients receiving BP administration occur after dental treatments such as tooth extraction, periodontal surgery and dental implants, and do not respond to conventional treatment modalities such as debridement, antibiotic therapy and hyperbaric oxygen therapy. No effective therapy for ONJ is established yet and empirical conservative therapy is recommended in the guidelines for prevention, diagnosis, and treatment of ONJ. Therefore, dentists and oral and maxillofacial surgeons need to recognize ONJ as a serious side effect of BPs and to make informed consent to the patients and a close consultation with medical oncologists for administration of BPs. PMID- 17272883 TI - [Periodontal regeneration by FGF2]. AB - Periodontitis, evoked by bacterial biofilm (dental plaque), progressively destroys the periodontal tissue supporting the teeth. Unfortunately, no conventional treatments can ever regenerate lost periodontal tissue or normal structure and functionality. Recently, basic fibroblast growth factor (FGF2) is winning attention from researchers in the field of periodontal tissue regeneration therapy. Topical application of FGF2 to the experimentally-prepared periodontal tissue defects in beagle dogs and non-human primates induced significant periodontal tissue regeneration with new cementum and new alveolar bone formation. Furthermore, the recent data of Phase II clinical trial demonstrated that FGF2 was efficacious in regenerating periodontal tissue. If we can generate an intelligent carrier for FGF2 in the nature of "scaffold", indications of FGF2 therapy would be dramatically increased. PMID- 17272884 TI - [Bone augmentation of dental implant treatment]. AB - Vertical and horizontal augmentation of the alveolar bone is often necessary to the placement of dental implants in inadequate bone volume areas. This article introduces surgical techniques (autogenous bone graft, maxillary sinus floor elevation, guided bone regeneration, distraction osteogenesis) for the reconstruction of atrophic bone prior to or simultaneous with implant placement. PMID- 17272885 TI - [Application of BMP to bone repair]. AB - Bone regeneration process involves upregulation of various bone morphogenetic proteins (BMPs) and their receptors, and several lines of evidence have demonstrated that BMP signaling plays a crucial role in bone regeneration. Recent research using conditional knockout mice of BMP-2 in limb revealed the essential role of BMP-2 during bone regeneration. Recombinant human BMPs and gene therapy of BMPs have been successfully applied to bone repair including application to dental implant. PMID- 17272886 TI - [Secondary osteoporosis. Pathogenesis of glucocorticoid-induced osteoporosis]. AB - Direct inhibitory effect of glucocorticoid (GC) on bone formation and promotion of apoptosis of bone cells are thought to be the major mechanism of glucocorticoid-induced osteoporosis (GIO). GC reduces not only bone mineral density (BMD) but also bone quality, therefore, patients with GIO have a higher risk of fracture than those with postmenopausal osteoporosis with the same level of BMD. Recently, GC has been shown to suppress a Wnt signal pathway which is essential for bone growth. PMID- 17272887 TI - Cost of treating patients with solitary cysticercus granulomas. PMID- 17272888 TI - Thrombolysis for stroke in India: miles to go... PMID- 17272889 TI - Transatlantic Odonto-Occipital Listhesis: the so-called basilar invagination. PMID- 17272890 TI - Thrombolytic treatment in acute cerebral infarction. PMID- 17272891 TI - How to optimize the evaluation of carpal tunnel syndrome in patients with polyneuropathy? PMID- 17272892 TI - Thrombolysis for acute ischemic stroke in India: overcoming the challenges. PMID- 17272893 TI - Tau and tauopathies. AB - Tau protein is a neuronal microtubule-associated protein (MAP), which localizes primarily in the axon. It is one of the major and most widely distributed MAPs in the central nervous system. Its biochemistry and molecular pathology is being increasingly studied. Tau is a key component of neurofbrillary tangles in Alzheimer's disease (AD). Disorders with neuronal, oligodendroglial or astrocytic filamentous tau inclusions are now grouped under the common rubric of tauopathies. The discovery of mutations in the tau gene, located on Chromosome 17 and its relationship to frontotemporal dementia with Parkinsonism (FTDP-17) has enhanced the importance of tau protein in cognitive neurology. Aberrant aggregates of tau have been documented in most of the neurodegenerative diseases with filamentous inclusions. The role of cerebrospinal fluid tau in the diagnosis of dementias is being investigated quite extensively. Recently, it has been shown that Abeta immunotherapy leads to the clearance of early tau pathology. It is becoming clearer that understanding tau better will lead to better understanding of many neurodegenerative diseases that may help develop interventional strategies. PMID- 17272894 TI - The role of sensory nerve conduction study of the palmar cutaneous nerve in the diagnosis of carpal tunnel syndrome in patients with polyneuropathy. AB - BACKGROUND: Conventional methods in the diagnosis of carpal tunnel syndrome (CTS) in patients with polyneuropathy (PNP) are insufficient. AIMS: We suggest that the comparison of the conduction of the median nerve with that of the neighboring peripheral nerves may be more beneficial in the diagnosis of entrapment neuropathy. SETTING AND DESIGN: The median nerve sensory conduction in healthy volunteers, in cases of CTS, PNP cases without CTS and in cases of PNP in whom clinical findings point to CTS, were compared by palmar cutaneous nerve (PCN) sensory conduction. MATERIALS AND METHODS: Comparative parameters were difference of PCN-1st digits' nerve conduction velocities (NCV), PCN/1st digit NCVs ratio, difference of 5th-2nd digits' NCVs and 5th/2nd digits' NCVs ratio. STATISTICAL ANALYSIS: The statistical analysis was performed by the SPSS package for statistics. Student t test and receiver operating characteristic were used. RESULTS: Although the ratio of PCN-1st digit did not differ significantly between the control group and the polyneuropathy group, there was a significant difference between CTS and PNP+CTS groups and the control group ( P < 0.001 and P < 0.001, respectively). The ratio of PCN-1st digit nerve conduction velocity was also significantly different between polyneuropathy and PNP+CTS groups ( P < 0.001). CONCLUSION: To diagnose CTS on a background of polyneuropathy in mild cases in which sensory conduction is preserved, the ratio of sensory nerve conduction velocities of the palmar cutaneous nerve and the median nerve 1st digit-wrist segment may be a criterion. PMID- 17272895 TI - Early nerve damage in leprosy: an electrophysiological study of ulnar and median nerves in patients with and without clinical neural deficits. AB - BACKGROUND: Peripheral nerve trunk involvement in leprosy is very common. However, by the time it becomes clinically manifest, the damage is quite advanced. If the preclinical nerve damage can be detected early, the deformities and disabilities can be prevented to a large extent. AIMS: To assess the electrophysiological functions of the ulnar and median nerve trunks in cases of clinically manifest leprosy with and without manifest nerve damage at different durations of nerve damage. MATERIALS AND METHODS: Electrophysiological functions of ulnar and median nerves were studied in leprosy patients, both normal and at different stages of disease and damage. PB cases, having disease for six months or less, without neurological symptoms and clinically normal appearing nerve. STATISTICAL METHODS: Mean was taken of different values. The changes in values of different parameters were expressed as percentage change with reference to the control values (increase or decrease). RESULTS: Reduced nerve conduction velocities and changes in latency and amplitude were observed. Changes in sensory nerve conduction were more pronounced. Sensory latencies and amplitude changes were more severe than motor latencies and amplitudes in cases with manifest muscle palsies. Changes in MB cases were less marked. CONCLUSIONS: Further studies are needed to identify parameters likely to be helpful in the diagnosis of early nerve damage. PMID- 17272896 TI - Practice patterns of neurology in India: fewer hands, more work. AB - BACKGROUND: India is a populous country housing over a billion people. Neurology as a specialty is being practiced in India for over 50 years but the number of physicians devoted to fulltime neurology is limited. This fact coupled with the privatized healthcare system and limited infrastructure has led to situations different from the more developed healthcare systems. AIM: To study the practice patterns of neurology in India. SETTING AND DESIGN: Questionnaire-based study. MATERIALS AND METHODS: Questionnaire was sent to 250 members of the Indian Academy of Neurology [sample size approximately 25%] using random number table. The responses were tabulated and analyzed. RESULTS AND CONCLUSIONS: The neurology group is small and hence is exposed to a large workload. The average number of patients seen daily by Indian neurologists is three to four times those seen by the United States and United Kingdom neurologists. Neurologists based at district places are more likely to see direct patients; whereas metropolitan neurologists see more referrals. Investigative facilities are available to neurologists but affordability is a concern. Clinical work leaves less time for academic and research activities, which the consultants are keen to participate in. In the privatized health system of India, emergency work constitutes a difficult area to cope with. The concept of single specialty group practice is welcomed by the majority with the idea of streamlining their work and life. These factors highlight an urgent need for increasing the neurology work force and argue for further involvement of primary physicians and internists in neurological care in India. PMID- 17272897 TI - Microsurgical anatomy of the posterior circulation. AB - CONTEXT: The microsurgical anatomy of the posterior circulation is very complex and variable. Surgical approaches to this area are considered risky due to the presence of the various important blood vessels and neural structures. AIMS: To document the microsurgical anatomy of the posterior circulation along with variations in the Indian population. MATERIALS AND METHODS: The authors studied 25 cadaveric brain specimens. Microsurgical dissection was carried out from the vertebral arteries to the basilar artery and its branches, the basilar artery bifurcation, posterior cerebral artery and its various branches. Measurements of the outer diameters of the vertebral artery, basilar artery and posterior cerebral artery and their lengths were taken. RESULTS: The mean diameter of the vertebral artery was 3.4 mm on the left and 2.9 mm on the right. The diameter of the basilar artery varied from 3-7 mm (mean of 4.3 mm). The length varied from 24 35 mm (mean of 24.9 mm). The basilar artery gave off paramedian and circumferential perforating arteries. The origin of the anterior inferior cerebellar artery (AICA) varied from 0-21 mm (mean 10.0 mm) from the vertebrobasilar junction. The diameter of the AICA varied from being hypoplastic i.e., CONCLUSIONS: The authors have documented the various anomalies as well as the differences of the anatomy in this area in the Indian population as compared to the Western literature. PMID- 17272898 TI - Economic evaluation of seizures associated with solitary cysticercus granuloma. AB - BACKGROUND: Patients with solitary cysticercus granuloma (SCG) develop acute symptomatic seizures because of the inflammatory response of the brain and the seizures are self-limiting. Thus seizure disorder associated with SCG provides a good model to study the total cost of illness (COI). MATERIALS AND METHODS: COI of new-onset seizures associated with SCG was studied in 59 consecutive patients registered at the epilepsy clinic. Direct treatment-related costs and indirect costs, man-days lost and wages lost were evaluated. The relative cost was calculated as the percentage of per capita gross national product (GNP) at current prices for the year 1997-1998. RESULTS: The total COI, for treating seizure disorder associated with SCG per the period of CT resolution of the lesion per patient was INR 7273.7 (US$ 174.66, I$ 943.16) and he/she would be spending 50.9% of per capita GNP The direct cost per patient was INR 5916 (US$ 137.14, 41.4% of per capita GNP). If the patient had received only AEDs for the period of resolution of CT lesion, the cost would be INR 5702.48 (US$132.2, 40% of per capita GNP). The extra expenditure on albendazole and steroid was INR 213.72 (US$ 4.95), 3.6% of the total direct cost and 20.7% of the medication cost. Indirect cost (average wage loss) per patient was INR 1312.7 (US$ 30.42) and it accounted for 9% of per capita GNP. The one-time expenditure at present costs (adjusted for inflation) to the nation to treat all the prevalence cases is to the tune of INR 1.184 billion (US$ 2.605) and 0.0037% of GNP. CONCLUSIONS: This study suggests that seizure disorder associated with SCG, a potentially preventable disorder, is a good model to study the total COI. The one-time expenditure at present costs to the nation to treat all the prevalence cases of seizure disorder associated with SCG is to the tune of INR 1.184 billion (US$ 2.605 million) and 0.0037% of GNP. PMID- 17272900 TI - Multi-minicore disease: a rare form of myopathy. AB - BACKGROUND: Multi-minicore disease is a rare form of myopathy characterized by slowly progressive or nonprogressive muscle weakness and characteristic multiple cores within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. MATERIALS AND METHODS: A ll cases of multi-minicore disease diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. RESULT: During a period of two years (January 2004 to December 2005), we received 985 muscle biopsies for various reasons. Of which, 15 were diagnosed as myopathies and four of which were of multi-minicore disease. Thus, multi-minicore disease comprises 0.40% of all muscle diseases and 26.6% of all myopathies. All were male and presented in early childhood (first decade of life) with generalized hypotonia and muscle weakness. All of them had dysmorphic facies and three had high arched palate. CPK levels were normal and EMG was myopathic except in one patient. Microscopic examination revealed minimal changes with Type I fibers' predominance but characteristic multiple cores in the myofibers. Ultrastructural examination showed both structured and unstructured cores. CONCLUSIONS: Multi-minicore disease, although a rare form of myopathies, should be suspected in children who present with generalized hypotonia and slowly progressive muscle weakness along with dysmorphic facies. PMID- 17272899 TI - Hyperacute thrombolysis with IV rtPA of acute ischemic stroke: efficacy and safety profile of 54 patients at a tertiary referral center in a developing country. AB - BACKGROUND: Given the constraints of resources, thrombolysis for acute ischemic stroke (AIS) is under evaluation in developing countries. Prothrombin time (PT), platelet count and activated partial thromboplastin time (aPTT) may not be feasible within the time window. AIM: To evaluate the safety and efficacy of thrombolysis in selected patients without the coagulation profile. DESIGN: Open, nonrandomized, observational study. MATERIALS AND METHODS: Fifty-four stroke patients were classified using TOAST criteria (large artery atherosclerotic = 13; cardioembolic = 12; small vessel occlusion = 22; other determined etiology =three; undetermined etiology = four). The mean time to reach emergency was 2.4h (1.15-3.4), the mean door to CT, 24 min (10-47) and the door to recombinant tissue plasminogen activator (r-tPA) injection, 26.8 min (25-67). The NIHSS scores ranged from 11 to 22 (mean = 15.5 +/- 2.7). Patients with history of liver or renal disease or those on anticoagulants were excluded. The PT, aPTT and platelet count were not done. Recombinant tissue plasminogen activator was administered at a dosage of 0.9 mg/Kg. RESULTS: Thirty-five patients (65%) significantly improved on NIHSS at 48 h (> or =4 points) (mean change = 10; range= 4-17). At one month, 43 (79%) improved on Barthel Index (mean change = 45%). One each developed small frontal lobe hemorrhage and recurrent stroke; one died of aspiration; and eight showed no improvement. CONCLUSIONS: Hyperacute thrombolysis was found useful and safe in selected patients with AIS even without the coagulation studies. PMID- 17272902 TI - A new autosomal recessive disorder of bilateral frontotemporal pachygyria without microcephaly: report of a case and review of literature. AB - Pachygyria is a disorder of neuronal migration. We report an Indian family with four siblings with developmental delay, infrequent seizures, normal head size and mild to moderate mental retardation. Two of them had bilaterally symmetrical frontotemporal pachygyria. Dysmorphism and neurological signs were absent in the affected subjects. Affected male and female siblings with normal parents suggests autosomal recessive mode of inheritance. We believe these cases represent a new autosomal recessive disorder of neuronal migration. Other similar cases of lissencephaly are reviewed. PMID- 17272901 TI - Pediatric intramedullary schwannoma without neurofibromatosis. AB - Pediatric intramedullary schwannoma without neurofibromatosis is extremely rare with only five cases reported so far. We present this rare finding in an 8-year old boy who presented with a sudden onset of weakness in all limbs. An intraoperative diagnosis of schwannoma enabled us to carry out a total excision of the tumor, which resulted in near complete recovery at 18 months follow-up. Although rare, this diagnosis should be considered when a child presents with a solitary intramedullary tumor, since its total resection can be achieved improving surgical outcome. PMID- 17272903 TI - Giant dumbbell foramen magnum neurinomas presenting as posterior neck masses: single-stage removal by posterior midline approach. AB - Two patients with giant dumbbell foramen magnum neurinomas are reported. The intradural component was located anterior to the cervicomedullary junction while the extradural and extraspinal portion of the tumor had grown large enough to present as a neck swelling. In both patients total surgical removal was achieved by a single-stage posterior midline approach. Both patients had complete neurological recovery. PMID- 17272904 TI - Intraosseous malignant peripheral nerve sheath tumor with focal epithelioid differentiation of the thoracic spine. AB - The authors describe an extremely rare case with malignant peripheral nerve sheath tumor (MPNST) with focal epithelioid differentiation presenting as an intraosseous lesion of the spine. A 75-year-old woman presented with progressive paraplegia caused by epidural mass arising from the posterior element of the T7 vertebra. At surgery, the lesion was noted to originate from the T7 vertebra and separate from the dura and spinal nerve roots. The patient died of tumor metastases to the lungs six months after the initial presentation. Histological diagnosis was MPNST. However, the tumor also contained cystic structures lined by epithelioid cells, requiring differentiation from synovial sarcoma. From the histological and immunohistochemical features, as well as the absence of SYT-SSX fusion gene expression, the diagnosis of MPNST with focal epithelioid differentiation was made. This is the first case report of intraosseous MPNST of the spine with a peculiar biphasic appearance. PMID- 17272905 TI - An interesting case report of Morvan's syndrome from the Indian subcontinent. AB - The French physician Augustine Marie Morvan first used the term 'la choriotae fibrillare' to describe a syndrome characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia and fluctuating delirium. There are no published reports of the condition from the Indian subcontinent. We report the first such case from the region. Our patient, a 24-year-old male, presented with easy fatigability and stiffness in both the calves for 18 months; continuous twitching of muscles of all four limbs and jaw for two months; hyperhydrosis, palpitations, urinary symptoms, burning dysesthesia in hands, insomnia and abnormal sleep behavior for about a month. Patient had bilateral hyper-reflexia with extensor plantar on the right and equivocal response on the left. Electromyography revealed continuous muscle fiber activity. Thyroid function test, electroencephalography, computerized tomography scan (head) and routine cerebrospinal fluid analysis were normal. The patient showed marked clinical and electrophysiological improvement on prednisolone along with symptomatic therapy over the next two months. PMID- 17272906 TI - Nemaline rod myopathy: a rare form of myopathy. AB - Nemaline rod myopathy (NM) is a rare form of congenital myopathy characterized by slowly progressive or nonprogressive muscle weakness and pathognomonic rod-like structures within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. All cases of NM diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. During a period of 1.5 years (Jan 2004 to June 2005), we received 750 muscle biopsies for various reasons. Of which, 15 were diagnosed as congenital myopathies and four as nemaline rod myopathies. Thus, NM comprises 0.53% of all muscle diseases and 22.6% of all congenital myopathies. All of them presented in childhood (first five years of life) with generalized hypotonia, feeding problems, repeated respiratory infections and muscle weakness. Both males and females were equally affected. The CPK levels were normal and EMG was myopathic. Microscopic examination revealed minimal changes but characteristic red-colored material was seen on modified Gomori trichrome staining which was immunopositive to alpha actinin. Ultrastructural examination confirmed this material to be nemaline rods. NM, although a rare form of congenital myopathies, should be suspected in children who present with generalized hypotonia, repeated chest infections and slowly progressive muscle weakness. This report highlights the importance of histochemistry and ultrastructural examination in the diagnosis of this entity, in the absence of the availability of methodology for genetic studies. PMID- 17272907 TI - Co-occurrence of radiological features of progressive supranuclear palsy and corticobasal degeneration. AB - We report an interesting case demonstrating co-occurrence of radiological features of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). The clinical features were typical of PSP but magnetic resonance imaging (MRI) showed both typical brainstem changes of PSP and an atypical pattern of cortical atrophy. While the MRI had markers of CBD, the clinical features were not classical of CBD. PMID- 17272908 TI - Huntington's disease in all (three) siblings and their one parent. AB - Three siblings (two girls and one boy) and their father are reported who developed Huntington's disease (HD). The two girls had onset at less than six years of age, while the boy started with symptoms at 12 years of age. The girl, the child number two, has expired and the youngest one is in a vegetative state. The elder brother is still mildly affected. The disease presented in a severe form and early in the females while it remained mild and presented late in the males. This is a rare disease involving all the three surviving siblings and their father. The diagnosis was confirmed after genetic testing. PMID- 17272909 TI - Expansion of intracerebral hematoma in patients with coagulopathy-some diagnostic pitfalls. PMID- 17272910 TI - Delayed and isolated intraventricular tension pneumocephalus after shunting for normal pressure hydrocephalus. PMID- 17272911 TI - Expansion of traumatic intracerebral hemorrhage: treatment implications with recombinant factor VIIa. PMID- 17272912 TI - Pregnancy-precipitated status epilepticus: a rare presentation of MELAS syndrome. PMID- 17272913 TI - Of a crash helmet and a cranial bolt: a design change recommendation. PMID- 17272914 TI - Co-occurrence of agenesis of internal carotid artery with contralateral arterio venous malformation. PMID- 17272915 TI - Spinal epidural air following multiple thorax trauma. PMID- 17272916 TI - Tincture benzoin as an antiseptic and adhesive for preoperative surgical preparation. PMID- 17272917 TI - Will diffusion tensor imaging assess rewiring in PVS' brains? PMID- 17272918 TI - Coexistence of Wilson's disease and neurofibromatosis type 1 in a 14-year-old boy. PMID- 17272919 TI - Langerhans cell histiocytosis of pituitary stalk. PMID- 17272920 TI - Band heterotopia in Zellweger syndrome (cerebro-hepato-renal syndrome). PMID- 17272922 TI - Dynamic changes in histone acetylation during sheep oocyte maturation. AB - The changes in histone acetylation are not always consistent in various cell types and at different developmental stages. We immunostained specific antibodies against acetylated lysine 9 of histone H3 and acetylated lysines 5 and 12 of histone H4 in an effort to understand the detailed changes in histone acetylation during sheep oocyte meiosis. We found that the acetylation fluorescence signals of H3/K9 and H4/K12 on chromatin appeared intensively in the germinal vesicle (GV), late-GV (L-GV), and germinal vesicle breakdown (GVBD) stages and became weak in metaphase I (MI); however staining reappeared in anaphase I-telophase-I (AI-TI) and metaphase II (MII). Furthermore, staining was detected in the first polar bodies. The fluorescence signals of H4/K5 first appeared in the MI stage and became intensive in the AI-TI stage; however they were barely detectable in MII stage chromosomes and first polar bodies. We conclude that the acetylation patterns of H3/K9 and H4/K12 during oocyte meiotic maturation are similar and that the pattern of H4/K5 is unique. PMID- 17272924 TI - Both PPARgamma and C/EBPalpha are sufficient to induce transdifferentiation of goat fetal myoblasts into adipocytes. AB - The present study was conducted to investigate whether goat fetal myoblasts with no inherent adipogenic potential can be induced to transdifferentiate into adipocytes. Goat fetal myoblasts were transiently transfected by the adipogenic transcription factors, peroxisome proliferator-activated receptor-gamma (PPARgamma) and CCAAT/enhancer-binding protein-alpha (C/EBPalpha). Both PPARgamma and C/EBPalpha were capable of inducing adipogenic transdifferentiation as indicated by the appearance of mature adipocytes when the transfected cells were cultured in adipogenic differentiation medium (ADM). Ectopic expression of PPARgamma induced endogenous C/EBPalpha expression and vice versa only when the cells were cultured in ADM. Removal of troglitazone, a PPARgamma agonist, from the ADM resulted in a dramatic decline in the number of adipocytes, indicating that PPARgamma stimulation is necessary to induce adipogenic transdifferentiation of goat fetal myoblasts. These results demonstrate for the first time that primary cultured myoblasts can be transdifferentiated into adipocytes. PMID- 17272923 TI - Involvement of stathmin in proliferation and differentiation of immortalized human endometrial stromal cells. AB - Uterine endometrial stromal cells differentiate into decidual cells during the late secretory phase of the menstrual cycle and pregnancy. However, the biochemical mechanisms of decidualization have yet to be definitively elucidated. In the present study, we transfected primary human endometrial stromal cell with a temperature-sensitive mutant of simian virus 40 large T antigen and thereby established an immortalized stromal cell line (EtsT) in order to examine the role of stathmin, a cytosolic phosphoprotein that regulates microtubule dynamics, in stromal cell differentiation. When treated with the decidual stimulus dibutyryl cAMP (db-cAMP) or forskolin, the fibroblastic cell-shaped EtsT cells transformed into large- and round-shaped cells and secreted large amounts of the decidual markers prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP 1). Analysis of the stathmin protein levels in the db-cAMP- and forskolin-treated EtsT cells revealed that the total and phosphorylated protein levels dropped as decidualization progressed. Suppression of stathmin expression by transfection with small interfering RNA (siRNA) suppressed EtsT cell proliferation. It also abolished db-cAMP-induced PRL and IGFBP-1 mRNA expression and protein secretion. Thus, stathmin expression can be considered an integral factor regulating the initial stage of the process of human endometrial stromal cell differentiation. PMID- 17272925 TI - Inhibition of stress-induced adrenocorticotropin and prolactin secretion mediating hypophysiotropic factors by antagonist of AMPA type glutamate receptor. AB - Glutamate is the dominant excitatory neurotransmitter in a large number of physiological processes including neuroendocrine regulation. Some pharmacological studies have shown that different subtypes of glutamate receptor, such as the N methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methy-4 isoxazolepropionic acid (AMPA) receptors, are involved in stress-induced adrenocorticotropin (ACTH) and prolactin secretion. However, the roles of the respective glutamate receptors and the mechanism of ACTH and prolactin secretion during stress via these receptors have not been investigated in detail. In the present study, we evaluated the role of AMPA-type glutamate receptor in ACTH and prolactin regulation under restraint stress in adult male rats. Male rats pretreated with a selective AMPA receptor antagonist, 2, 3-dihydroxy-6-nitro-7 sulfamoyl-benzo(f)quinoxaline (NBQX; 50 microg), through a lateral ventricle cannula were stressed by immobilization. Administration of NBQX inhibited ACTH and prolactin secretion in response to restraint stress. However, NBQX had no significant effects on the activity of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine biosynthesis, as measured by the accumulation of 3, 4 dihydroxyphenylalanine (DOPA). In addition, administration of NBQX suppressed stress-induced prolactin secretion in the male rats pretreated with alpha-MT, an inhibitor of dopamine synthesis, and infused with dopamine solution (2.5 microg/200 microl/10 min). These results indicated that the effects of NBQX on prolactin secretion might be mediated by non-dopamine mechanisms. The contents of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the median eminence (ME) of the male rats decreased during restraint stress; however, the fluctuations in CRH and AVP were eliminated by NBQX administration. These results suggest that stress-induced ACTH and prolactin release mediated by neurotransmission via AMPA receptors might be partly attributable to hypophysiotropic regulatory factors in the hypothalamus. PMID- 17272926 TI - The effect of estrogen on phosphorylation of prolactin in the mouse pituitary gland. AB - Several studies have indicated that prolactin (PRL) assumes oligomeric, proteolytically cleaved, phosphorylated and glycosylated forms. Phosphorylated PRL (PPRL) is considered to be the most important posttranslationally modified form in the rat. In the present study, we examined whether or not PRL is present in the mouse pituitary gland in the phosphorylated form. Mouse pituitary PRL was digested with acid phosphatase, resolved by two-dimensional gel electrophoresis, stained with Coomassie brilliant blue, and then immunoblotted against the anti PRL, anti-phosphoserine and anti-phosphothreonine antibodies. We also examined whether PRL is phosphorylated by protein kinases and semi-quantified the ratios of PPRL to PRL in the pituitary gland. The results indicated that three types of PRL are present in the pituitary glands of both male and female mice. One was non phosphorylated (isoform 1), and the other two were immunoreactive to anti phosphoserine (isoform 2) and/or anti-phosphothreonine (isoform 3) antibodies. The ratio between isoforms 2 and 1 of the 30-day-old female mice was higher than that of the 20-day-old female mice. However, the ratios among the three isoforms in the male pituitary glands did not differ with age. The ratio of PPRL to isoform 1 was obviously reduced after ovariectomy (OVX), and it recovered with estrogen replacement. These results suggest that estrogen influences PRL phosphorylation in female mice. PMID- 17272927 TI - Treatment of porcine oocytes with MEM vitamins during in vitro maturation improves subsequent blastocyst development following nuclear transfer. AB - This study was carried out to investigate the effects of minimum essential medium (MEM) vitamins during in vitro maturation (IVM)/in vitro culture (IVC) of porcine nuclear transfer (NT) embryos on subsequent developmental capacity in vitro. Porcine cumulus-oocyte complexes (COCs) were divided into five groups, matured for 44 h in maturation medium with various concentrations of MEM vitamins (0, 0.05, 0.1, 0.2 and 0.4%), and observed for maturation rate. Also, COCs were matured in NUSU-23 media without MEM vitamins for 44 h and cultured in PZM-3 media with various concentrations of MEM vitamins (0, 0.05, 0.4 and 1.0%) for 6 days following nuclear transfer. Factorial (IVM/IVC) experiments were also performed in NCSU-23 medium with or without 0.05% MEM vitamins and PZM-3 medium with or without 0.4% MEM vitamins. They were then tested by examining in vitro development of the porcine reconstructed embryos. The maturation rates of the COCs treated with the MEM vitamins did not differ significantly among the MEM vitamin-treated groups. Addition of vitamins to culture medium did not affect development of porcine reconstructed embryos in vitro. However, addition of low concentrations of MEM vitamins only to maturation medium increased (P<0.05) the proportion of NT embryos developing into blastocysts compared with the control group. Addition of MEM vitamins to IVC medium did not enhance the developmental rate compared with the control group. Thus, addition of MEM vitamins to IVM medium could improve subsequent blastocyst development of porcine NT embryos. PMID- 17272928 TI - The role of interleukin-6 in the regulation of granulosa cell apoptosis during follicular atresia in pig ovaries. AB - More than 99% of follicles in mammalian ovaries undergo a degenerative process known as atresia, and only a few follicles actually ovulate during follicular growth and development. Follicular selection mostly depends on granulosa cell apoptosis, but the molecular mechanism behind the regulation of this selective atresia is still largely unknown. In the present study, to examine whether or not interleukin-6 (IL-6), a multifunctional cytokine, is involved in apoptosis during atresia in pig ovaries, the expression of IL-6 mRNA in granulosa cells was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR). The level of mRNA decreased during atresia. Enzyme-linked immunosorbent assay (ELISA) showed that the level of IL-6 protein in follicular fluid also decreased during atresia. Moreover, recombinant human IL-6 upregulated the expression of an intracellular apoptosis inhibitor, cellular FLICE-like inhibitory protein long form (cFLIP(L)), in cultured cells derived from human granulosa cells. It is possible that IL-6 is produced in the granulosa cells of healthy follicles, that it increases the cFLIP(L) level, and cFLIP(L) then prevents apoptotic cell death. PMID- 17272929 TI - Reproductive phenotypes in mice with targeted disruption of the 20alpha hydroxysteroid dehydrogenase gene. AB - In the corpus luteum of rats and mice, 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catalyzes the conversion of progesterone to a biologically inactive metabolite, 20alpha-dihydroprogesterone (20alpha-OHP). The reduction of progesterone by 20alpha-HSD is believed to be important for functional luteolysis in these rodent species. In addition to the corpus luteum, expression of 20alpha HSD has been demonstrated in tissues such as the placenta, endometrial epithelia, and fetal skin, although the roles it plays in the latter tissues remain to be determined. To determine the contribution of 20alpha-HSD to functional luteolysis and to the rodent reproductive system more generally, we generated a strain of mice with targeted disruption of the 20alpha-HSD gene. In the 20alpha-HSD-/- mice we obtained, which lacked the genomic region essential for catalytic reaction, neither 20alpha-HSD activity in the corpus luteum nor an increase in the serum concentrations of 20alpha-OHP during pseudopregnancy or pregnancy was detected. The durations of the estrous cycle, pseudopregnancy, and pregnancy were significantly prolonged in the 20alpha-HSD-/- mice, although the serum progesterone levels decreased to levels low enough for delivery of pups at term of pregnancy. In addition, the number of pups, especially live pups, was markedly decreased in the 20alpha-HSD-/- mice. These findings suggest that the role of 20alpha-HSD in functional luteolysis is relatively minor but that it is involved in the survival of newborn mice. PMID- 17272930 TI - [Multiple pregnancies]. AB - Twin and multiple pregnancies carry an increased risk compared to singleton pregnancies and a challenge in obstetrical management. Multiple births are a worldwide issue, especially due to the increased incidence in several countries in the last few years. Prenatal care and obstetrical management call for specific solutions due to specific risks in such pregnancies. The present papers try to give both an overview and to offer a deeper insight into selected problems of obstetrical care for multiple pregnancies. PMID- 17272932 TI - [Genetic counseling in multiple pregnancies]. AB - Genetic counseling in cases of multiple pregnancies shows marked differences compared to singleton pregnancies. The rising rate of multiple pregnancies and its association with advanced maternal age has expanded the need for prenatal diagnosis in twins and higher-order gestations. However, the request for invasive prenatal diagnostic procedures often differs in multiple and singleton pregnancies. This is in particular true when the multiple pregnancy occurred after assisted reproductive technology. In case of twin pregnancies, the distinction between a mono- and dizygotic pregnancy may facilitate the decision about obtaining a single or two samples. Discordant anomalies pose a special problem. Discordant anomalies are in rare instances even observed in monozygotic pregnancies. Here, we summarize the clinical, analysis-related and ethical problems regarding genetic counseling in multiple pregnancies. PMID- 17272931 TI - [Multiple pregnancies after ART: problems and possible solutions]. AB - Multiple pregnancies following an assisted reproduction technique (ART) should be seen as a complication, and for that reason they should be avoided. In contrast to singleton pregnancies following ART, the multiple pregnancies are associated with a higher prenatal, neonatal and maternal risk; furthermore this results in a financial burden for the health care system. This paper gives an overview of the latest literature and different attempts of European countries, trying to reduce the multiple pregnancy rate. An efficient reduction is only possible by single embryo transfers. There should be strict and cross-national regulation for the choice of women who should have a transfer of more than one embryo. PMID- 17272933 TI - [Obstetrical care of multiple pregnancies up to the 24th week of pregnancy--a survey]. AB - The number of multiple pregnancies increases, as does the knowledge of their (patho)physiology, and of diagnostic and therapeutic difficulties. The role of sonography in prenatal medicine has developed dramatically over the years, especially in assessing and treating fetuses in multiple pregnancies. Therefore this article reflects this development. It gives an overview of the current knowledge and literature. PMID- 17272934 TI - [Water contamination and infection rate after water births]. AB - OBJECTIVE: This study aimed at examining the water of the birthing tub for pathogenic germs and at comparing the infection rates of the children born conventionally. METHOD: In a prospective study, the germs found in the water of 300 water births were determined . The tub water was sampled twice: sample A was taken after filling the tub with tap water, sample B after the water delivery. In addition, the paediatrician documented any signs of infection of the neonates during their hospital stay. RESULTS: The A samples contained Legionella in 29%, Pseudomonas aeruginosa in 22%, enterococci in 18%, colibacilli in 32% and Escherichia coli in 8%. After fitting a filter system, no Legionella was detected any more. P. aeruginosa was found in only 3% of the samples. In the B samples, we found an increased contamination by colibacilli in 81%. A marked burden with E. coli was detected in 58% of the samples. Due to a clinically an biochemically suspected beginning infection, 1.15% of the water-born children (14 out of 1,215) were given antibiotics. In contrast, 2.30% of the conventionally born neonates (19 out of 817) were treated with antibiotics. CONCLUSION: It is evident that during the bearing-down phase faeces are discharged into the birthing tube and that the water is contaminated mainly by E. coli and colibacilli, but also slightly by Staphylococcus aureus. The contamination of the tap water by Legionella and Pseudomonas could clearly be reduced by installation of a filter system into the supply hose of the birthing tub. Neonatal infections were not more frequent after water births than after conventional deliveries. PMID- 17272936 TI - [Recommendations for estrogen and progesterone substitution in climacteric and postmenopause]. PMID- 17272935 TI - [Primary malignant melanoma of the vagina--case report and review of the literature]. AB - The primary malignant melanoma of the vagina is a very rare tumor with less than 300 cases reported worldwide. Metastatic melanomas of the vagina are even rarer and only 5 cases have been reported so far. We describe the case of patient with a melanoma of the left side of the vagina with a tumor size of 6 cm and a tumor invasion of 2.5 cm. At the time of diagnosis there were no signs of nodal metastases in the positron emission tomography. In the literature, wide local excision with adjuvant radiotherapy is recommended, and radical surgery with adjuvant radiotherapy as second-line therapy. Both procedures show similar 5-year survival rates. To reduce the risk of metastases, we had planned an immunotherapy with interferon-alpha, which has been shown to improve relapse-free and overall survival in patients with high-risk cutaneous melanoma. Unfortunately, the cancer was found to have heavily metastasized 6 months later; the patient therefore received a palliative chemotherapy with dacarbazine and thalidomide. PMID- 17272937 TI - Beckenbodenchirurgie und weibliche Sexualfunktion im Blickfeld. Bericht von der 31. Jahresversammlung der International Urogynecological Association, Athen, 6. 9. September 2006. PMID- 17272938 TI - Selective decline in information processing in subgroups of multiple sclerosis: an 8-year longitudinal study. AB - Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system (CNS) that causes white matter and cortical lesions over many years. The CNS is selectively affected by the disease with a great variety of symptoms between patients. In this study, we describe the impact on various aspects of cognition over an 8-year follow-up period in 31 consecutive MS patients subgrouped as relapsing remitting (RR) MS, secondary progressive (SP) MS, and primary progressive (PP) MS. Results showed a differential pattern of cognitive decline already at baseline in speed of information processing. During the follow-up, a pronounced decline occurred in speed of information processing, finger-motor speed, copying geometrical designs, episodic memory, and visuospatial short-term memory. A striking difference was observed between a marked decline in visual reaction time, whereas no significant change was seen in auditory reaction time. In contrast, there was no time-related decline in verbal abilities. However, an initial marked cognitive impairment predicted further cognitive decline over the 8-year follow-up. Information-processing tests were found to be an especially strong predictor of long-term cognitive decline. In addition, high EDSS score at follow-up was associated with decline in information processes. Results also showed that SP-MS patients deteriorated significantly more than the other two groups, particularly in visual compared to auditory information processing. To conclude, cognitive decline appeared particularly in SP-MS patients and in visual information processing. PMID- 17272939 TI - How does zinc supplementation benefit anorexia nervosa? AB - BACKGROUND: A randomized controlled trial of zinc supplementation in anorexia nervosa (AN) reported a two-fold increase of the rate of increase of body mass index (BMI) in the zinc group. Zinc is inexpensive, readily available and free of significant side effects. However, oral zinc supplementation is infrequently prescribed as an adjunctive treatment for AN. Understanding the mechanism of action of zinc may increase its use. HYPOTHESIS: Low zinc intake, which is very common in AN, adversely affects neurotransmitters in various parts of the brain, including gamma-amino butyric acid (GABA) and the amygdala, which are abnormal in AN. Zinc supplementation corrects these abnormalities, resulting in clinical benefit in AN. CONCLUSIONS: Oral administration of 14 mg of elemental zinc daily for 2 months in all patients with AN should be routine. PMID- 17272940 TI - Can cognitive exercises help treat anorexia nervosa? AB - Cognitive remediation therapy (CRT) is used as an intervention for people with brain lesions and psychosis. This case report demonstrates the possible benefits of introducing CRT into treatment packages for anorexia nervosa (AN). In our previous work, we reported that people with AN demonstrate inflexibility in cognitive set-shifting tasks. Weight gain alone does not improve the neuropsychological profile in set-shifting tasks. This case report illustrates how training programmes can address problems in cognitive rigidity. We acknowledge the limitations of case studies, however, this is a starting point in exploring the possibilities of introducing CRT as part of the treatment of AN. PMID- 17272941 TI - The drive for muscle leanness: a complex case with features of muscle dysmorphia and eating disorder not otherwise specified. AB - Muscle dysmorphia has been described as a subtype of body dysmorphic disorder in which an individual experiences severe body image disturbance related to muscularity. The current case is of a 20-year-old man who describes a history of muscle dysmorphia in which the nature of the body image concern is related to leanness (i.e., muscularity in the absence of body fat), as opposed to increasing muscle mass, which is how muscle dysmorphia has typically been characterized in the literature. The case illustrates the need to consider this additional facet of body image when diagnosing muscle dysmorphia. PMID- 17272942 TI - An open trial of an intensive summer day treatment program for severely overweight adolescents. AB - This open trial examined the feasibility and usefulness of treating adolescents with a body mass index (BMI) > or =95th percentile in a 6-week day treatment program within a psychiatric outpatient setting. Sixteen adolescents, ages 12-15, attended a 6-week multidisciplinary summer day treatment program. Outcome measures include pre- and post-program assessments of BMI, body fat, laboratory measures, nutritional status, physical activity, mood and eating disorder symptoms, motivation, self-esteem and quality of life. BMI, waist/hip circumferences, blood pressure, heart rate, and body fat did not change significantly from baseline to week 6. Fasting glucose decreased significantly from baseline to week 6, but there were no significant changes in other laboratory measures. The teen-rated feelings subscale of the Peds Quality of Life Scale improved. Self-esteem, as measured by the Rosenberg Self- Esteem Scale, indicated a strong trend towards improvement, and motivation measures also showed a trend for improvement. These findings suggest that a brief, intensive intervention for overweight adolescents may yield meaningful changes in quality of life, self-esteem, and motivation, even in the absence of significant weight loss. PMID- 17272943 TI - Cognitive distortions in obese patients with or without eating disorders. AB - In the normal weight population, cognitive distortions are more often found in people with eating disorders such as anorexia and bulimia than in a control population. With these cognitive distortions, weight and body image become central elements in self-esteem. This exploratory study investigated cognitive distortions in obese patients suffering from binge eating disorder or not. The hypothesis was that the patients suffering from binge eating disorder would have more cognitive distortions. Twenty-nine obese women (11 without and 18 with binge eating disorder) and 13 non-obese female controls were selected. To evaluate the cognitive distortions, subjects completed the Mizes Anorectic Cognitions-Revised (MAC-R) questionnaire. Contrary to our hypothesis, we found no difference in evidence between the two obese groups with or without eating disorders. Possible perspectives for treatment are discussed. PMID- 17272944 TI - Comparison of orlistat and sibutramine in an obesity management program: efficacy, compliance, and weight regain after noncompliance. AB - To describe the comparative efficacy of orlistat and sibutramine in an obesity management program, with specific attention to compliance and weight regains after noncompliance. We prospectively evaluated 182 obese patients who were randomized to treatment with orlistat (n=98) or sibutramine (n=84) along with the diet and exercise prescriptions. Compliance (or compliant patient) was defined as adherence to scheduled visit times (at 3- month intervals) and following the prescribed drug regimen. A telephone survey was conducted in case of noncompliance. Significant body weights improvements were seen in both treatment groups. Patients lost a mean of 7.6+/-2.8% and 10.5+/-2.9% of initial body weights after a mean drug use of 8.8+/-5.7 and 8.3+/-3.7 months in the orlistat and sibutramine groups, respectively (p<0.05 vs. initial body weight). Patients in the sibutramine group lost more weight than the orlistat group (p<0.05). A total of 102 patients (56%) were compliant (53.1% in the orlistat group and 59.5% in the sibutramine group). Factors associated with compliance included weight reduction of more than 5% in the first 3 months and adherence to physical activity. Higher initial body weight, prior anti-obesity therapy, number of concurrent medications, and comorbidity were associated with noncompliance. Weight regains in noncompliant patient were a mean of 5.2+/-5.1 kg after a mean period of 9.2+/-4.2 months in the orlistat group, and a mean of 6.1+/-3.8 kg after a mean period of 9.1+/-3.9 months in the sibutramine group (p<0.05 vs. last visit for both groups, p>0.05 between groups). Both drugs in an obesity management program can achieve substantial weight loss. However, noncompliance and rebound weight regain after noncompliance are considerable problems. PMID- 17272945 TI - Attachment in anorexia nervosa: an exploration of associations with eating disorder psychopathology and psychiatric symptoms. AB - Previous research on attachment and eating disorder has to a great extent presupposed direct links between states of mind with respect to attachment and eating disorder diagnoses. The authors provide a brief review stating that no such association can be found in current literature. The authors suggest that the association might exist on the level of eating disorder pathology and psychiatric symptoms, rather than diagnostic level. Based on 20 Adult Attachment Interviews coded with the Dynamic-Maturational method from patients diagnosed with anorexia, the authors explore the associations between attachment and diagnostic subgroups, eating disorder psychopathology (Eating Disorder Inventory--2nd edition), and psychiatric symptoms. All patients were coded within the range of insecure attachment. State of mind with respect to attachment did not differentiate between diagnostic subgroup and eating disorder pathology. Individuals classified as dismissing reported higher levels of anxiety-related distress than those classified as preoccupied or mixed dismissing/preoccupied. A high frequency of unresolved traumas and losses was found. The findings support previous reports of high frequencies of insecure attachment and unresolved traumas in anorexic patients. The high level of anxiety-related stress in the dismissing group lead the author to suggest that attachment plays a role in the patient's handling of distress following the eating disorder, rather than in the disorder itself. PMID- 17272946 TI - School prevention program for eating disorders in Croatia: a controlled study with six months of follow-up. AB - The main purpose of this pilot study was to evaluate the efficacy of a schoolbased program of eating disorder prevention on a sample of young adolescents in Croatia. The program was designed to reduce dietary restraint and preoccupation with shape and weight. One hundred and thirty-nine students (69 boys and 70 girls; mean age 12.8 years) were evaluated; 75 participated in the program (experimental group) and 64 formed the control group. Outcome measures included eating disorder attitudes, dieting behavior, selfesteem, and knowledge of the topics covered by the program. Outcome measures were evaluated one week before the intervention, one week afterwards, and during a follow-up of 6 months. The program significantly reduced eating disorder attitudes and dieting behavior, and improved knowledge in the female experimental group. A significant and positive effect on eating disorders attitude and knowledge, but not on dietary habits, was noticed in the male experimental group. No significant effects were observed in the control group. The findings of this prevention program give encouraging results and should be evaluated in further studies on larger samples. PMID- 17272947 TI - Factors affecting dropout in outpatient eating disorder treatment. AB - OBJECTIVE: To evaluate the incidence and effects of factors potentially influencing eating disordered patients' dropping out of outpatient cognitive behavioural therapy (CBT). METHOD: Sixty-seven (64 female, 3 male) patients with eating disorders participated in the study. All patients followed a multidisciplinary team approach for a median period of 9 months. Several factors potentially affecting dropout were retrospectively assessed prior to treatment. RESULTS: The dropout rate was significantly higher in patients with purging anorexia nervosa (AN) compared to those with restrictive AN, bulimia nervosa and eating disorder not otherwise specified (33% vs. 27%, 25% or 21%, respectively, p<0.05). Among several factors influencing dropout, there was a significant association of patient low cooperativeness, purging episodes, restrictive eating, use of several weight control practices and psychiatric co-morbidity in patients who dropped out compared to completers (all p<0.05). CONCLUSIONS: In outpatient eating disorder treatment, non-compliance and premature interruption of therapy are affected primarily by factors which are related to patients' attitude and behaviour. These factors should be carefully addressed in patients with eating disorders to improve outcome. PMID- 17272948 TI - Resolving a disagreement in a clinical team: overcoming conflicting views about the role of family therapy in an outpatient treatment programme for anorexia nervosa. AB - In the Adolescent Psychiatry Department at the Institut Mutualiste Montsouris, Paris, as is also observed in the literature, the outcome for anorexic patients can sometimes be catastrophic, regardless of treatments proposed. This disturbing finding led us to reassess our therapeutic treatment strategies, in an effort to improve patient outcome. The multidimensional treatment program implemented in the Department includes parent counselling, but not the whole family in a family therapy procedure. It has been demonstrated better outcome for patients who underwent family therapy in comparison to patients who underwent individual therapy. This raised the question of whether family therapy could improve our outpatient programme. This paper describes here how a research programme was developed to resolve a disagreement in our clinical team as to whether family therapy should be added to the existing care programme. The paper describes the difficulties encountered by our team, and the experimental design chosen to resolve the debate. Data will not be set out here. PMID- 17272949 TI - Challenging previous conceptions of vegetarianism and eating disorders. AB - The purpose of this study was to replicate and expand upon previous research that has examined the potential association between vegetarianism and disordered eating. Limitations of previous research studies are addressed, including possible low reliability of measures of eating pathology within vegetarian samples, use of only a few dietary restraint measures, and a paucity of research examining potential differences in body image and food choice motives of vegetarians versus nonvegetarians. Two hundred and fifty-six college students completed a number of measures of eating pathology and body image, and a food choice motives questionnaire. Interestingly, no significant differences were found between vegetarians and nonvegetarians in measures of eating pathology or body image. However, significant differences in food choice motives were found. Implications for both researchers and clinicians are discussed. PMID- 17272950 TI - Reformulation of the Children's Eating Attitudes Test (ChEAT): factor structure and scoring method in a non-clinical population. AB - The primary aims of this study were to empirically test the factor structure of the Children's Eating Attitudes Test (ChEAT) through both exploratory and confirmatory factor analyses and to interpret the factor structure of the ChEAT within the context of a new scoring method. The ChEAT was administered to 728 children in the 2nd through 6th grades (from five schools) at two different time points. Exactly half the students were male and half were female. To the best of our knowledge, this is the first study to empirically test the merits of an alternative 6-point scoring system as compared to the traditionally used 4-point scoring system. With the new scoring procedure, the skewness for all factor scores decreased, which resulted in increased variance in the item scores, as well as the total ChEAT score. Since the internal consistency of two factors in a recently proposed model was not acceptable (<0.60), this model did not adequately fit our data. Thus, exploratory and confirmatory factor analyses were conducted. A 6-factor solution based on a 20-item version was found to best fit the data and have the best internal reliability. The six factors were labeled: 1) overconcern with body size, 2) dieting, 3) food preoccupation, 4) social pressure to gain weight, 5) vomiting, and 6) caloric awareness and control. The obtained factor solution had considerable overlap with the original factor analysis performed on the 26-item Eating Attitudes Test and with the factor structure of the ChEAT reported by previous investigations. Intercorrelations among the factors suggested three higher order constructs. These findings indicate that the ChEAT subscales may be sufficiently stable to allow use in non-clinical samples of children. PMID- 17272951 TI - [Historical perspectives, definition and categorization of food allergy]. PMID- 17272952 TI - [Epidemiology of food allergy (its comparison between Japan and other countries)]. PMID- 17272953 TI - [Recent progress of biological agents in collagen-vasucular diseases]. PMID- 17272954 TI - [Remodeling of the upper airways]. PMID- 17272955 TI - [What should we learn from animal models?]. PMID- 17272956 TI - [Drug-induced lung injury]. PMID- 17272957 TI - [Four cases of wheat-dependent exercise-induced anaphylaxis with negative gluten cap-rast score]. AB - BACKGROUND: Either omega-5 gliadin or high molecular weight glutenin is known to be a major allergen in wheat-dependent exercise-induced anaphylaxis (WDEIA). It is generally considered that gluten specific IgE score is more reliable than that of wheat specific IgE score for the diagnosis of WDEIA. Our aim was to verify the significance of gluten specific IgE in the diagnosis of WDEIA. METHODS: We evaluated the result of gluten CAP-RAST score and omega-5 gliadin specific IgE score on four WDEIA patients who visited our hospital during the years 2004 and 2005, whose diagnosis were onfirmed by prick tests, immunoblot tests and provocation tests. RESULTS: Contrary to our expectations, all four patients showed negative gluten CAP-RAST scores, however all patient's omega-5 gliadin specific IgE scores were positive. CONCLUSION: Our results suggest that gluten specific CAP-RAST score is unreliable in the diagnosis of WDEIA. On the other hand omega-5 gliadin specific IgE score is possibly a better candidate as a diagnostic tool for WDEIA. PMID- 17272958 TI - [A case of occupational contact urticaria and oral allergy syndrome due to seafood]. AB - A 20-year-old woman was referred for evaluation after about 2 years of recurrent episodes of localized urticaria during handling of several kinds of raw fish in a sushi shop, where she had worked part-time for 2 years. She had also experienced allergic symptoms such as itching and swelling of her lips, generalized urticaria, laryngeal tightness, stridor and dyspnea immediately after ingestion of raw and cooked seafood, including sole, horse mackerel, sea eel and shellfish, over the previous 1 year before referral. Skin prick tests and blood test for specific IgE antibodies were positive for many kinds of seafood, including sole, horse mackerel, sea eel, eel, crab, and abalone, which belonged to different taxonomic phyla, including Chordata, Arthropoda, and Mollusca. A challenge with a piece of broiled sole induced swelling of the lips, obstruction of the larynx, difficulty with deglutition, and abdominal pain. In addition, serum-specific IgE antibodies to two major fish allergens, parvalbumin and collagen, were detected by ELISA, suggesting that allergic symptoms could be induced by many kinds of seafood in the present patient. She was therefore diagnosed with occupational contact urticaria and oral allergy syndrome due to seafood. At the time of this report, the present patient had been followed for one year and no reactions have occurred since she started to avoid the causative types of seafood. PMID- 17272959 TI - [Cholinergic urticaria successfully treated by immunotherapy with partially purified sweat antigen]. AB - A 24-years-old man was referred to our University Hospital because of one and a half-year history of disabling symptoms related to physical exertion. Multiple small round-shaped wheals with severe itch were induced by exercise, warmth and psychological stress. These symptoms were resistant to histamine H1-receptor antagonists. Similar eruptions were induced by sauna-bathing, and skin test with autologous sweat showed a flare and wheal reaction. Incubation of his peripheral blood leukocytes with partially purified sweat antigen evoked marked histamine release, indicating that he has been IgE-sensitized to an antigen(s) in human sweat. Specific immunotherapy using partially purified sweat antigen was performed every other week. Both pruritus and wheals improved gradually, and the reactivity of his peripheral blood leukocytes against sweat antigen decreased as immunotherapy was proceeded. Specific immunotherapy using sweat antigen may be valuable for patients with cholinergic urticaria with type I hypersensitivity to sweat antigen(s). PMID- 17272960 TI - Aberrant central nervous system responses to the Valsalva maneuver in heart failure. AB - Heart failure (HF) is associated with aberrant autonomic nervous system (ANS) activity, with altered responses to blood pressure and breathing challenges that appear to reflect abnormal central nervous system function. The authors used functional magnetic resonance imaging (fMRI) to determine whether the Valsalva maneuver, an ANS challenge, would show abnormal responses in ANS regulatory areas of the brain in HF. Brain fMRI signal changes in 5 HF patients (left ventricular ejection fraction, 0.15+/-0.08; age, 50+/-10 years) and 14 controls (age, 47+/-11 years) were assessed during 3 successive Valsalva maneuvers. The hypothalamus, hippocampus, putamen, amygdala, mid-cingulate, right insula, and cerebellar cortex showed exaggerated and phase-shifted fMRI responses in HF; other areas showed inverted signals from those found in controls. Central ANS control areas have altered phase, extent, and direction of responses to Valsalva maneuvers in a small sample of HF patients. These findings suggest that therapeutics that address neuroprotective aspects may be useful interventions for the condition. PMID- 17272961 TI - A trainee's perspective on cardiovascular care. PMID- 17272962 TI - Amlodipine added to quinapril vs quinapril alone for the treatment of hypertension in diabetes: the Amlodipine in Diabetes (ANDI) trial. AB - This randomized, comparative, parallel-group trial investigated strategies of blood pressure (BP)-lowering in patients with diabetes and hypertension. Patients not reaching goal BP (<130/80 mm Hg) after 4-week open-label treatment with quinapril 20 mg/d (n=374) received 40 mg/d quinapril (n=167) or 20 mg/d quinapril plus amlodipine besylate (5 mg/d; n=162) for 6 weeks. Patients receiving combination therapy vs monotherapy had significantly greater reductions in mean +/- SE sitting systolic BP (9.9+/-1.0 mm Hg vs 4.3+/-1.1 mm Hg; P<.001) and diastolic BP (6.5+/-0.6 mm Hg vs 2.7+/-0.6 mm Hg; P<.001). No significant differences between groups were observed in percentage of patients achieving goal BP (10.1% with combination therapy vs 8.2% with monotherapy). A clinically neutral effect was observed on high-sensitivity C-reactive protein in both groups. Treatments were well tolerated; fewer than 3% of patients in any group discontinued due to treatment-emergent or treatment-related adverse events. In diabetic hypertensive patients, 20 mg/d quinapril plus 5 mg/d amlodipine besylate was a more effective BP-lowering strategy than monotherapy with 40 mg/d quinapril. PMID- 17272963 TI - Bayesian methods for highly correlated exposure data. AB - Studies that include individuals with multiple highly correlated exposures are common in epidemiology. Because standard maximum likelihood techniques often fail to converge in such instances, hierarchical regression methods have seen increasing use. Bayesian hierarchical regression places prior distributions on exposure-specific regression coefficients to stabilize estimation and incorporate prior knowledge, if available. A common parametric approach in epidemiology is to treat the prior mean and variance as fixed constants. An alternative parametric approach is to place distributions on the prior mean and variance to allow the data to help inform their values. As a more flexible semiparametric option, one can place an unknown distribution on the coefficients that simultaneously clusters exposures into groups using a Dirichlet process prior. We also present a semiparametric model with a variable-selection prior to allow clustering of coefficients at 0. We compare these 4 hierarchical regression methods and demonstrate their application in an example estimating the association of herbicides with retinal degeneration among wives of pesticide applicators. PMID- 17272964 TI - Effects of donepezil adjunctive treatment to ziprasidone on cognitive deficits in schizophrenia: a double-blind, placebo-controlled study. AB - The objective of this study was to examine the effects of adjunctive treatment with the acetylcholinesterase inhibitor, donepezil, on cognitive deficits and psychopathology in schizophrenic patients treated with the antipsychotic, ziprasidone. The design of the study was double blind, placebo controlled, and longitudinal. Patients were treated with ziprasidone for 8 weeks, thereafter randomized to 4 months of double-blind adjunctive treatment with either donepezil (dose, 5-10 mg) or placebo. The severity of psychopathology (PANSS) and the cognitive deficits were examined at baseline and after 4 months. A total of 21 schizophrenic patients were enrolled, of whom 11 patients completed the trial (donepezil, n = 7; placebo, n = 4). There were no within- or between-group differences in changes on the Positive and Negative Syndrome Scale scores or a global cognitive score. Within-group improvements (all at trend level P = 0.07) were seen in the placebo group on Trail-Making Test B, immediate verbal recall, and set-shifting errors. The donepezil group showed a significant deterioration on planning efficiency (P = 0.04). Between-group differences were found between the lack of improvement in immediate verbal recall in the donepezil group and the improvement in the placebo group (P = 0.02), and between the deterioration of planning efficiency in the donepezil group and the stability in the placebo group (trend level, P = 0.07). Linear regression analyses showed that neither baseline psychopathology scores, baseline levels of cognitive deficits, nor psychopathology changes over time accounted for these changes in cognitive scores. The study found no evidence of improved cognition after treatment with donepezil, although the conclusions that can be drawn are limited by the small sample size. PMID- 17272965 TI - High-dose vitamin B6 decreases homocysteine serum levels in patients with schizophrenia and schizoaffective disorders: a preliminary study. AB - Vitamin B6 plays an essential role in the normal functioning of the central nervous system. Normal homocysteine (Hcy) serum level is maintained by remethylation of Hcy to methionine by enzymes that require folic acid and vitamin B12 and by catabolism to cysteine by a vitamin B6-dependent enzyme. These findings may be consistent with the hypothesis that the vitamin B6 status may influence plasma Hcy levels. The aims of this preliminary study were (1) to determine whether a correlation exists between Hcy and vitamin B6 levels in patients with schizophrenia and schizoaffective disorders and (2) to investigate whether treatment with high-dose vitamin B6 may reduce Hcy levels in these patients. METHODS: In this preliminary study, we enrolled 11 patients with schizophrenia or schizoaffective disorders (7 men and 4 women; mean age +/- SD, 50 +/- 12 years) receiving high doses of vitamin B6 treatment (1200 mg/d) for 12 weeks. Blood samples for the assessment of pyridoxal-5-phosphate and Hcy serum levels were obtained at baseline and after 12 weeks of treatment. RESULTS: Age was significantly positively correlated with Hcy levels at baseline (r = 0.392, P = 0.004). All other parameters, including diagnosis, disease duration, and pyridoxal-5-phosphate serum level, were not correlated with Hcy serum levels at baseline. After vitamin B6 treatment, Hcy serum levels significantly decreased (14.2 +/- 3.4 vs. 11.8 +/- 2.0 micromol/L, respectively, t = 2.679, P = 0.023); this decrease being statistically significant in men but not in women. CONCLUSIONS: High doses of vitamin B6 lead to a decrease in Hcy serum level in male patients with schizophrenia or schizoaffective disorder. PMID- 17272966 TI - Clinical efficacy of a single afternoon dose of effervescent levodopa-carbidopa preparation (CHF 1512) in fluctuating Parkinson disease. AB - A possible cause of motor fluctuations in patients with Parkinson disease is the erratic drug absorption. In a randomized double-blind double-dummy study of melevodopa (levodopa methyl ester), a highly soluble levodopa pro-drug plus carbidopa (CHF 1512) was compared to a standard formulation of levodopa/carbidopa (LD/CD) in 74 fluctuating Parkinson disease patients. The first afternoon, LD/CD tablet was substituted with an equimolar dose of CHF 1512. The study lasted 4 weeks and was followed by an 8-week (optional) open phase. The primary efficacy variable was latency to "on." Patients randomized to receive CHF 1512 had a significative shorter latency to "on" than those randomized to LD/CD and a similar "on" duration. The safety profile of CHF 1512 was also comparable with LD/CD. PMID- 17272967 TI - The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine. AB - OBJECTIVE: : Ingestion of the nonproteinic amino acid theanine (5-N ethylglutamine) has been shown to increase oscillatory brain activity in the so called alpha band (8-14 Hz) during resting electroencephalographic recordings in humans. Independently, alpha band activity has been shown to be a key component in selective attentional processes. Here, we set out to assess whether theanine would cause modulation of anticipatory alpha activity during selective attentional deployments to stimuli in different sensory modalities, a paradigm in which robust alpha attention effects have previously been established. METHODS: : Electrophysiological data from 168 scalp electrode channels were recorded while participants performed a standard intersensory attentional cuing task. RESULTS: : As in previous studies, significantly greater alpha band activity was measured over parieto-occipital scalp for attentional deployments to the auditory modality than to the visual modality. Theanine ingestion resulted in a substantial overall decrease in background alpha levels relative to placebo while subjects were actively performing this demanding attention task. Despite this decrease in background alpha activity, attention-related alpha effects were significantly greater for the theanine condition. CONCLUSION: : This increase of attention related anticipatory alpha over the right parieto-occipital scalp suggests that theanine may have a specific effect on the brain's attention circuitry. We conclude that theanine has clear psychoactive properties, and that it represents a potentially interesting, naturally occurring compound for further study, as it relates to the brain's attentional system. PMID- 17272968 TI - A double-blind, randomized, crossover study of prosigne versus botox in patients with blepharospasm and hemifacial spasm. AB - There is a lack of evidence on the clinical efficacy and safety of the recently released Chinese botulinum toxin serotype A (Prosigne) for the treatment of focal dystonias and hemifacial spasm. Determining a more precise role of Prosigne in the treatment of such conditions is of paramount importance, because botulinum toxin type A treatments have a huge economic implication in health services, especially in developing countries. The aim of our study was to compare the efficacy and safety of Prosigne in the treatment of blepharospasm and hemifacial spasm in comparison to Botox. We performed a double-blind, randomized, crossover study enrolling 26 patients. There were no significant differences between Prosigne and Botox regarding subjective global improvement, response onset, efficacy duration, and incidence and severity of adverse events. Our results suggest that Prosigne and Botox are comparable with respect to efficacy and safety for the short-term treatment of blepharospasm and hemifacial spasm. PMID- 17272969 TI - Two years' follow-up of rivastigmine treatment in Huntington disease. AB - OBJECTIVES: In a previous short-term study, rivastigmine has shown a mild effect in ameliorating cognitive impairment and slowing motor deterioration in patients affected by Huntington disease (HD). The aim of the present study was to assess the long-term efficacy of rivastigmine on motor and cognitive impairment in HD patients. METHODS: This was an open-label, controlled study with blinded rates: 11 HD patients were evaluated after 2 years under 6 mg rivastigmine treatment versus 6 patients sorted as controls. In basal conditions and after 2 years' follow-up, patients were submitted to the Mini-Mental State Examination, Marsden and Quinn Chorea Severity Scale, Total Functional Capacity score, Abnormal Involuntary Movement Scale, and the motor and functional section of the Unified Huntington Disease Rating Scale. RESULTS: Patients treated with rivastigmine showed a significant improvement of global motor performances and chorea in comparison with the control group, with a trend toward a reduction of functional disability and cognitive impairment. CONCLUSIONS: On the basis of the long-term follow-up of HD patients, rivastigmine exerted a significant improvement of motor performances with a positive trend on cognitive and functional scales. The results of this study suggest long-term efficacy of rivastigmine in HD, which needs to be confirmed in larger series. PMID- 17272970 TI - Neuroleptic malignant syndrome from aripiprazole in an agitated pediatric patient. AB - OBJECTIVE: Neuroleptic malignant syndrome was induced by aripiprazole in a 12 1/2 year-old boy. The patient had a history of reactive airway disease, pervasive developmental disorder, and learning disability. METHOD: The patient was interviewed and examined, and additional history was taken from the medical records. The Naranjo adverse drug reaction rating scale was applied. RESULTS: The patient developed neuroleptic malignant syndrome 2 days after starting aripiprazole 10 mg/d. This patient had no history of exposure to dopamine blocking drugs or selective serotonin reuptake inhibitors or of neurological disorder, movement disorder, or substance use. Aripiprazole discontinuation and supportive treatment led to resolution. The Naranjo scale indicates high probability of neuroleptic malignant syndrome from aripiprazole. CONCLUSIONS: Aripiprazole can rapidly induce neuroleptic malignant syndrome in adolescents. PMID- 17272971 TI - Tegaserod in constipation associated with Parkinson disease. AB - Impaired gastrointestinal motility and constipation are common problems in Parkinson disease (PD). Many patients with PD continue to experience constipation, despite multiple interventions (dietary modification, bulk-forming agents, stool softeners, and laxatives). Tegaserod is a 5-hydroxytryptamine type 4 agonist that stimulates gastrointestinal motility and is approved for the treatment of chronic idiopathic constipation. We report our experience with tegaserod in 5 patients with PD-associated constipation. Tegaserod was well tolerated and improved both bowel movement frequency and stool consistency in most of our patients. Further trials with tegaserod are warranted in PD associated constipation. PMID- 17272972 TI - Optic neuropathy related to hydrogen peroxide inhalation. AB - Optic neuropathy related to toxins is a complex, multifactorial disease potentially affecting individuals of all ages. We report a case of presumed toxic optic neuropathy secondary to H2O2 exposure. This has not been previously reported, and the temporal relationship of the exposure to the optic neuropathy is compelling, although not definite, evidence of a causal relationship. PMID- 17272973 TI - Fluoxetine for persistent developmental stuttering. AB - Stuttering is a disturbance in the normal fluency and time patterning of speech. Developmental stuttering (DS), with or without associated psychiatric illness, is the most common form and includes all cases with gradual onset in childhood that are not the result of acquired brain damage. Persistent developmental stuttering (PDS) is DS that has not undergone spontaneous or speech therapy-induced remission. Adults in speech therapy behavioral programs will often show regression and even total relapse if they stop practicing. This case report deals with a patient of PDS who responded significantly to treatment with fluoxetine. PMID- 17272974 TI - About the anti-Parkinson equivalency of levodopa and dopamine agonists. PMID- 17272976 TI - Targeted therapies and non-small-cell lung cancer: new developments. PMID- 17272977 TI - Positron emission tomography in nonsmall cell lung cancer. AB - PURPOSE OF REVIEW: Positron emission tomography (PET) has become a major adjunct to structural imaging for nonsmall cell lung cancer. Established indications are the differential diagnosis of lung nodules, as well as mediastinal lymph node and extrathoracic staging. RECENT FINDINGS: More details for small or faint pulmonary nodules became available--information of interest in the era of lung cancer screening trials, in which PET might help to reduce unwanted invasive procedures for benign findings. The strength of PET in mediastinal staging (its high negative predictive value) was confirmed in a randomized study, in which PET reduced the number of invasive procedures without loss of accuracy in staging. Isolated positive lesions that are decisive for radical compared with palliative treatment should be confirmed by other tests, as they may be benign or due to second primary cancer. PET with integrated computed tomography (CT) may guide modern radiotherapy, by improving radiation fields. Integrated PET-CT is a promising tool in the indication for surgery in stage IIIA-N2 patients after induction treatment. Predictive values for lymph node downstaging become in acceptable ranges and PET response in the primary tumor could be clearly linked to pathologic response and survival. SUMMARY: In recent years, PET has seen further refinements in established indications and definition of new indications. PMID- 17272978 TI - Surgery of non-small cell lung cancer in the elderly. AB - PURPOSE OF REVIEW: The aim of this review is to analyze recent evidence for optimal treatment of elderly patients with non-small cell lung cancer, focusing on surgery, and possibly to foresee the future strategies to apply in these patients. RECENT FINDINGS: Surgery in elderly patients affected by non-small cell lung cancer is safe and feasible when careful preoperative respiratory and cardiac studies have been carried out and the disease has been properly staged. The surgical treatment is not to be denied in elderly patients due to age per se, but when a major contraindication to surgery has been recognized. Long term survival for elderly patients with early stage lung cancer treated by anatomical pulmonary resection is comparable to the survival rate of younger patients. Pneumonectomy, extended surgical procedure or preoperative induction chemotherapy are major risk factors for an increased postoperative morbidity and mortality rate. When co-morbidities are present or a patient is 80 years or older, there is evidence that a non-anatomical resection can be performed without affecting long term results. SUMMARY: Due to the aging of the general population, elderly patients will become a large percentage of the cases of non-small cell lung cancer to be treated. Implementing preoperative cardiologic studies and redefining selective respiratory criteria specifically could dramatically improve results. PMID- 17272979 TI - Neoadjuvant chemotherapy in the treatment of nonsmall-cell lung cancer. AB - PURPOSE OF REVIEW: To review the recent evidence regarding the potential benefit on the outcome of neoadjuvant chemotherapy in patients with early-stage nonsmall cell lung cancer and compare this evidence with the theoretical advantages and disadvantages of the approach. RECENT FINDINGS: The available evidence has mostly not yet been published in full manuscript form and should be interpreted cautiously. The observed gain in survival with neoadjuvant treatment is not consistent with expectations. Literature-based meta-analyses, however, estimate a gain in survival of at least 6% after 5 years. Neoadjuvant chemotherapy results in clinical downstaging in approximately 40-60% of the patients and pathological complete response rate in 5-10%. Neoadjuvant chemotherapy does not reduce the number of pneumonectomies. As expected, its compliance is better compared with adjuvant treatment. Neoadjuvant chemotherapy does not delay surgery or result in an increased hospital stay or rate of perioperative complications, when compared with immediate surgery. Neoadjuvant regimens should be platinum-based and at least three cycles of chemotherapy should be administered. SUMMARY: Neoadjuvant chemotherapy in early-stage nonsmall-cell lung cancer should not yet be offered outside of clinical trials and will in the future have to be compared with adjuvant chemotherapy. PMID- 17272980 TI - Combined targeted therapies in non-small cell lung cancer: a winner strategy? AB - PURPOSE OF REVIEW: Current treatment modalities provide limited improvement in the natural course of lung cancer, and prognosis remains poor. Lung cancer is a malignancy with great molecular heterogeneity. The complexity of the signalling process leading to cancer cell proliferation and to the neoplastic phenotype supports the necessity of interfering at different stages to avoid cancer cell resistance to therapy. RECENT FINDINGS: Use of several agents with multiple growth factor receptor or intracellular targets has shown encouraging results in phase I and II clinical trials in non-small cell lung cancer. ZD6474 is a dual epidermal growth factor receptor and vascular endothelial growth factor receptor 2 small-molecule tyrosine kinase inhibitor; sorafenib is an oral kinase inhibitor of Raf-1 and is also active against vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor beta, and c-KIT. Sunitinib is a vascular endothelial growth factor receptor 1, 2, and 3, c-KIT, and platelet derived growth factor receptor alpha and beta tyrosine kinase inhibitor. SUMMARY: Combined use of epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib and the humanized vascular endothelial growth factor receptor monoclonal antibody bevacizumab in advanced, chemotherapy-refractory non-small cell lung cancer has shown promising results. PMID- 17272981 TI - Small cell lung cancer and targeted therapies. AB - PURPOSE OF REVIEW: Small cell lung cancer is a chemosensitive malignancy, yet long-term survival remains elusive for the majority of patients. Here, we report on progress in evaluating novel targeted therapies for the treatment of this disease. RECENT FINDINGS: Interferons, matrix metalloproteinase inhibitors, thalidomide, bevacizumab, ZD6474, imatinib, gefitinib, oblimersen and aplidine have all entered clinical trial in patients with small cell lung cancer. Immunotherapy approaches targeting cell surface antigens such as CD-56 (BB10901) and GD3 ganglioside are also being evaluated. Interferons, matrix metalloproteinase inhibitors, imatinib and gefitinib have failed to demonstrate efficacy for this disease. Preliminary data for thalidomide are promising and so results from trials of other antiangiogenics such as bevacizumab and ZD6474 are awaited with interest. SUMMARY: Although the promise of targeted therapy has yet to be realized in patients with small cell lung cancer, the number of agents available for evaluation provides new optimism that progress will be made over the next decades. PMID- 17272982 TI - Early melanoma diagnosis: a success story that leaves room for improvement. AB - PURPOSE OF REVIEW: Early diagnosis has the greatest potential for short-term impact on melanoma mortality. We highlight recent trends in early melanoma detection and address the related challenges and opportunities. RECENT FINDINGS: Significant strides have been made in the early diagnosis of melanoma. Success has been achieved through improved awareness of early signs of melanoma and identification of high-risk cohorts. Detection pressure, however, may also be resulting in the diagnosis of indolent disease, leading to unnecessary morbidity and cost. A looming imbalance of supply and demand for melanoma detection services is anticipated with the aging of the baby boom generation. Prioritization of other preventive services and a growing emphasis on cosmetic dermatology are anticipated to exacerbate this imbalance. While a paucity of hard data have precluded adoption of formal screening recommendations for melanoma, general consensus supports opportunistic screening and identification of high risk individuals who may benefit from specialized surveillance with dermoscopy and whole-body photography. Research is needed to distinguish biologically indolent and aggressive melanoma, to develop and test evolving technologies to aid diagnosis, and to assess the utility of specific public health strategies for melanoma detection. SUMMARY: Significant strides have been made in early melanoma detection, but multiple challenges remain. PMID- 17272983 TI - Current topics in melanoma. AB - PURPOSE OF REVIEW: New approaches to melanoma are emerging. This review summarizes developments over the past 12 months. RECENT FINDINGS: Surgical, chemotherapeutic, immunologic and targeted therapies for melanoma are evolving. Sentinel lymph node sampling is now accepted as the standard of care for patients with intermediate thickness primary melanomas. Temozolomide continues to be widely used as part of combination therapy, and recent evidence suggests that a combination of temozolomide and interferon-alpha may be superior to temozolomide alone. Meanwhile, temozolomide and thalidomide carries unacceptable thrombosis risk. In the area of immunotherapy, anti-CTLA-4 continues to show promise, but special attention must be paid to gastrointestinal toxicity. Interferon-alpha, in addition, has shown efficacy in the neoadjuvant setting with inflammatory infiltrates demonstrated in tumors. A better understanding of the complex genetic regulation of melanoma cell growth is emerging and this is expected to lead to the development of novel targeted therapies. SUMMARY: Research is producing a more complete understanding of melanoma genetics and immune regulation. These are beginning to produce therapeutics that are impacting clinical practice. PMID- 17272984 TI - Melanoma immunology: past, present and future. AB - PURPOSE OF REVIEW: Metastatic melanoma is a disease for which no effective therapeutic options have been developed during the last 30 years with the possible exception of high dose interferon-alpha in the adjuvant setting of stage III patients. The immunotherapy approach was initiated decades ago using cell based vaccines and adoptive immunotherapy with functionally ill-defined lymphocytes. This paper aims to evaluate the last three decades of research in melanoma immunotherapy and to provide insights in the future of this strategy. RECENT FINDINGS: Thanks to the development of knowledge in basic and applied immunology, clinical studies of immunotherapy have been followed by trials based on molecular characterization of melanoma antigens and availability of ex-vivo assays allowing the quantitative assessment of the immune response against the given vaccine and against patient tumor cells. This second generation of immunotherapy trials, along with additional preclinical studies, while not yet resulting in a convincing clinical outcome, provided a wealth of data on immunogenicity of different melanoma antigens, mechanism of antigen presentation and factors that impair immune recognition of melanoma cells. SUMMARY: We discuss how this information will be exploited for designing new and more successful clinical trials of both active and adoptive antigen-specific immunotherapy of metastatic melanoma patients. PMID- 17272985 TI - Blood or marrow transplantation for mantle cell lymphoma. AB - PURPOSE OF REVIEW: Mantle cell lymphoma is a generally incurable disease for which blood or marrow transplantation is frequently considered. This review assesses the more recent literature on high-dose therapeutic approaches for mantle cell lymphoma. RECENT FINDINGS: The benefit of transplantation is most apparent in first remission. Autologous transplantation can prolong event-free and possibly overall survival, although no plateau has been demonstrated in the survival curve. A randomized controlled trial demonstrated a significant event free survival advantage to upfront autologous transplantation compared with interferon maintenance. The relative merit of autologous versus allogeneic transplantation remains to be better defined. SUMMARY: The role of transplantation for mantle cell lymphoma is controversial, as the impact on overall survival is unclear. Transplantation should be considered early in the disease course. Elimination of minimal residual disease through in-vivo purging of stem cells may translate into more durable remissions. Nonmyeloablative allogeneic transplantation and high-dose radioimmunotherapy are topics of ongoing investigation. PMID- 17272986 TI - Transplantation for amyloidosis. AB - PURPOSE OF REVIEW: High-dose chemotherapy increasingly is being used for the management of patients with immunoglobulin light-chain amyloidosis. We describe nearly 300 patients who had treatment combining high-dose chemotherapy and stem cell transplantation at Mayo Clinic and review the recent literature. RECENT FINDINGS: We review outcomes, engraftment data, and predictors of early mortality. The survival benefit of transplantation, however, has not been verified in a phase III clinical trial. SUMMARY: Partial response rates and complete response rates are prognosticators of survival for patients with amyloidosis. These rates are much higher for patients who receive high-dose therapy and transplantation. PMID- 17272987 TI - Natural killer cell alloreactivity in allogeneic hematopoietic transplantation. AB - PURPOSE OF REVIEW: This review will focus on the translation of natural killer cell recognition of missing self into the clinical practice of allogeneic hematopoietic transplantation and discuss how it has opened innovative perspectives in the cure of leukemia. Allogeneic hematopoietic stem cell transplantation from a human leukocyte antigen-matched sibling can cure leukemia but 75% of patients do not have a matched donor, one alternative source of stem cells includes full haplotype mismatched family members. As haploidentical transplantation must be extensively T cell depleted to prevent lethal graft versus-host disease, it cannot rely on donor T cells for the graft-versus leukemia effect. Mismatched transplantation, however, triggers alloreactivity mediated by natural killer cells which is based upon 'missing self recognition'. RECENT STUDIES: Recent studies using preclinical murine models of haploidentical transplantation demonstrated that conditioning with alloreactive natural killer cells ablates the recipient immune system and leukemia cells. In the clinical setting of mismatched hematopoietic stem cell transplantation, donor versus recipient natural killer cell alloreactivity has been associated with better outcome, particularly in patients with acute myeloid leukemia who are transplanted in remission. SUMMARY: Given the benefits of natural killer cell alloreactivity, it is expected that it will encourage greater use of haploidentical transplants for the large numbers of leukemia patients without matched donors. PMID- 17272988 TI - Thrombotic microangiopathy following allogeneic hematopoietic stem cell transplantation. AB - PURPOSE OF REVIEW: The aim of this article is to assess the current understanding and uncertainties about the evaluation and management of thrombotic microangiopathy that occurs following allogeneic hematopoietic stem cell transplantation. RECENT FINDINGS: Current data may not be sufficient to establish posttransplantation thrombotic microangiopathy as a discrete clinical or pathologic entity, distinct from other well recognized transplant-related complications. Analysis of case series of posttransplantation thrombotic microangiopathy illustrates uncertainties regarding incidence, risk factors, diagnosis, treatment, and survival. These studies have suggested the lack of efficacy of plasma exchange treatment and have identified other transplant related complications, such as acute graft-versus-host disease and opportunistic infections, as the predominant causes of death in patients who had been diagnosed with posttransplantation thrombotic microangiopathy. Recently consensus diagnostic criteria were proposed by two independent groups to provide more uniform identification of patients with posttransplantation thrombotic microangiopathy; these criteria may result in a clearer definition of this syndrome. SUMMARY: Posttransplantation thrombotic microangiopathy remains a diagnostic and therapeutic challenge. Further studies are required to determine if it is a specific entity and to define its relation to other transplant-related complications. PMID- 17272989 TI - Current world literature. Lung and mediastinum. PMID- 17272991 TI - Hepatic granulomas. AB - Hepatic granulomas were present in 3.7% of liver biopsies from a 6-year Greek study. The majority of cases were due to autoimmune disease (primary biliary cirrhosis), followed by sarcoidosis and idiopathic causes. Infections were infrequent. This profile is similar to series from the USA, Ireland and Scotland. It contrasts dramatically with series from Turkey and Saudi Arabia where infectious aetiologies form the majority of cases, and autoimmune cases are not reported. Tuberculosis and schistosomiasis are the most prevalent infections. The patient sex and age differ strikingly in some series. The series were tabulated for easy comparison. PMID- 17272992 TI - Wilson's disease: an old disease keeps its old secrets. AB - Wilson's disease is a rare condition characterized by a defect in biliary excretion of copper, due to a mutation of both alleles of "Wilson's disease" gene (ATP7b gene). Many different mutations have been identified in affected patients. Since the clinical presentation of the disease is highly heterogeneous, it has been suspected that this variability could be related to different phenotypes. In this paper, Folhoffer et al. report a series of 109 Hungarian patients with Wilson's disease. The authors identified 8 novel, previously unreported, mutations of ATP7b gene in their population. However, 17% of patients with an established diagnosis of Wilson's disease still did not have any identifiable mutation. Since not all exons were analyzed, more studies are needed to identify the corresponding mutations. Overall, the authors failed to document any genotype phenotype correlation suggesting that non genetical factors are involved in the clinical variability of the disease. PMID- 17272993 TI - Hepatic granulomas: a 6-year experience in a single center in Greece. AB - BACKGROUND: Hepatic granulomas have been reported in 2-15% of unselected liver biopsies, with a wide clinical profile responsible for their presence. To date, no series concerning the prevalence and the etiology of granulomas from Greece has been reported. OBJECTIVES: To evaluate the prevalence and the etiology of hepatic granulomas and to investigate whether there has been an alteration in distribution of diagnoses in our series compared with those published so far in the literature. STUDY: The results of liver biopsy specimens performed in a Department of Medicine, between 1999 and 2004, were retrospectively reviewed and the cases revealing hepatic granulomas had their medical notes and the liver biopsies recorded. RESULTS: Over the study period, 1768 liver biopsies were performed. Hepatic granulomas were identified in 66 (3.7%). Of those, 51 were female with a mean age of 57 years (range 34-74 years) and 15 were male with a mean age of 42 years (range 18-78 years). Autoimmune liver diseases including primary biliary cirrhosis, overlap syndrome and autoimmune hepatitis accounted for the majority of cases (68%), followed by sarcoidosis (7.5%), chronic hepatitis B virus and hepatitis C virus infection (7.5%), idiopathic (6%), drugs (3%) and other miscellaneous causes (7.5%). CONCLUSIONS: Our series showed that autoimmune liver diseases, mainly primary biliary cirrhosis was the most common cause of granuloma formation, a finding rather similar to that stated in the studies from Western countries. A rather small number of idiopathic cases were recorded. Chronic viral hepatitis and sarcoidosis rates were equal, a finding possibly reflecting a fairly high proportion of viral hepatitis in our sample. PMID- 17272994 TI - Novel mutations of the ATP7B gene among 109 Hungarian patients with Wilson's disease. AB - BACKGROUND/AIMS: Diagnosis of Wilson's disease may be difficult in patients presenting with liver disease and in asymptomatic siblings. The aim of the present study was to assess the impact of genetic testing for diagnosis of the disease in a large cohort (n=109) from Hungary. PATIENTS/METHODS: One hundred and nine patients with Wilson's disease were studied (65 men and 44 women; mean age at onset of symptoms: 20+/-9 years). Diagnosis of the disease was based on typical clinical and laboratory features (all had a Wilson's disease score of >or=4). H1069Q was assessed by the semi-nested polymerase chain reaction-based restriction fragment length polymorphism assay. H1069Q heterozygotes and H1069Q negative samples were then screened for mutations (on exons 6 to 20) by denaturating high-performance liquid chromatography and than sequenced on a genetic analyser. RESULTS: Twenty-three different mutations were found. H1069Q was the most frequent mutation in Hungary, detected in 77 patients (71%). Fourteen further known mutations were found by sequencing. We identified eight new mis-sense mutations not described before: N676I, S693Y, Y715H, M769L, W939C, P1273S, G1281D and G1341V. In 36/109 patients (33%) the diagnosis of Wilson's disease was established by adding mutational analysis. The Kayser-Fleischer ring was more frequent in H1069Q homozygous patients and their mean age at the time of diagnosis was higher than in patients heterozygous or negative for H1069Q. CONCLUSION: Eight novel mutations in addition to the 15 that are already known were found in Hungarian patients with Wilson's disease. Our results underline the importance and usefulness of genetic testing for patients presenting with liver disease and for family screening. PMID- 17272995 TI - Intrafamilial transmission of hepatitis B in Tuzla region of Bosnia and Herzegovina. AB - OBJECTIVE: To determine (i) the prevalence of HBV infection in families of confirmed chronic carriers, (ii) possible routes of transmission and risk factors for the intrafamilial transmission, (iii) vaccination rate among family members of chronic carriers and (iv) family members with highest risk for infection. METHODS: A total of 172 family members of 67 hepatitis B surface antigen chronic carriers were tested for hepatitis B markers; 716 first-time blood donors from the same area were used as controls. RESULTS: Prevalence of hepatitis B surface antigen was higher (P<0.001) among family members of index cases (12.2%; 21/172) than among controls (3.6%; 26/716) with relative risk of 3.3 (95% confidence Intervals=1.9-5.8; P<0.05). Rate of exposure among family members was 37.8% (65/172); only 8.7% (15/172) had been vaccinated for hepatitis B virus. Difference (P<0.001) in exposure existed among family members; exposure increased with age (rhos=0.34; P<0.001). Prevalences of hepatitis B surface antigen positivity and hepatitis B virus exposure were higher among parents of index cases (P<0.005) and among offspring of female index cases (P<0.001). There were more (P<0.001) hepatitis B surface antigen-positive family members among those with mother-children relationship with index case (13/31; 41.9%) than among those with father-children (19/85; 22.4%) and horizontal (siblings and spouses) relationship (2/56; 3.6%). Significantly more (P<0.001) hepatitis B surface antigen-positive and hepatitis B virus-exposed offspring were found in families where only mother was hepatitis B surface antigen positive. Among family members of HBeAg-positive cases more hepatitis B surface antigen-positive cases and hepatitis B virus-exposed cases have been found (P<0.001). Combination of HBeAg positivity and female sex of index case significantly increased risk for chronic carriage among family members (relative risk=24.06; 95% confidence interval=8.88 65.21; P<0.05). CONCLUSION: In the area studied, both horizontal and vertical transmission exists, but maternal route is predominant. Female sex, HBeAg positivity of index carrier and presence of hepatitis B surface antigen-positive mother inside family increased risk for hepatitis B surface antigen positivity and exposure among family members. Vaccination rate of family members of index cases is alarmingly low. PMID- 17272997 TI - Autonomic dysfunction in primary biliary cirrhosis correlates with fatigue severity. AB - BACKGROUND AND AIMS: Autonomic dysfunction has previously been described in primary biliary cirrhosis patients. In nonhepatic diseases, fatigue is associated with autonomic dysfunction and impaired baroreflex sensitivity. Here, we investigate the prevalence of autonomic dysfunction using highly sensitive detection modalities and its relationship with fatigue in both noncirrhotic and cirrhotic primary biliary cirrhosis patients. METHODS: Autonomic reflex tests were performed, using continuous blood pressure and electrocardiograph measurement in 47 primary biliary cirrhosis patients and age and sex-matched controls. Fatigue was measured using the primary biliary cirrhosis-40. RESULTS: In all, 100% of precirrhotic and 81% of cirrhotic primary biliary cirrhosis patients exhibited autonomic dysfunction. Valsalva ratio and 30 : 15 ratio (measures of parasympathetic autonomic dysfunction) were significantly lower in primary biliary cirrhosis patients than in controls (valsalva ratio: 1.42 vs. 1.57; P=0.01, 30 : 15: 1.1 vs. 1.2; P=0.01). Blood pressure drop on standing (sympathetic autonomic dysfunction) was greater in the primary biliary cirrhosis group (31+/-22 vs. 23+/-15 mmHg; P=0.03). Valsalva phase IV size was similar between primary biliary cirrhosis patients and controls, however, time to phase IV was significantly longer (P=0.01), suggesting adrenergic failure. Increasing fatigue was associated with impaired baroreflex sensitivity and an earlier, bigger phase IV (sympathetic overactivity). No significant differences were seen, between cirrhotic and noncirrhotic patients. CONCLUSION: The prevalence of autonomic dysfunction in primary biliary cirrhosis patients is significantly higher than has previously been thought to be the case. Indeed, when sensitive detection modalities are used, it is found to be almost universal at all stages of the disease process. Fatigue in primary biliary cirrhosis is associated with abnormalities of autonomic function. PMID- 17272996 TI - Interferon-alpha therapy within the first year after acute hepatitis C infection in hemodialysis patients: efficacy and tolerance. AB - BACKGROUND: Interferon monotherapy significantly reduces the chronicity rate of acute hepatitis C in nonuremic patients. In this clinical study, we evaluated the efficacy and tolerance of interferon-alpha therapy for acute hepatitis C in hemodialysis patients. METHODS: Patients with acute hepatitis C, established on the basis of seroconversion to anti-hepatitis C virus and the presence of hepatitis C virus RNA, received a low dose of interferon-alpha (3 MU three times per week) for 12 months or a high dose (5 MU three times per week, preceded by a daily induction dose) for 6 months. Response to treatment was defined as undetectable hepatitis C virus RNA at the end of treatment and sustained virological response was defined as persistent negative hepatitis C virus RNA 6 months after the end of treatment. RESULTS: Twenty-three patients were treated, 16 with a low dose of interferon-alpha and seven with a high dose. At the end of treatment, hepatitis C virus RNA was undetectable in 16/23 patients (70%). Of these, 6/23 patients (26%) relapsed and 10/23 (43%) maintained a sustained virological response (38% in lower doses vs. 57% in higher doses). Treatment was well tolerated and only three patients discontinued therapy (13%). CONCLUSION: Interferon-alpha within the first year after acute hepatitis C in hemodialysis patients was found to be safe and effective, inducing a sustained virological response in 43% of cases. This study supports the routine indication of acute hepatitis C treatment with interferon-alpha for hemodialysis patients, and higher doses administered for a shorter period of time should be tried according to the tolerance of the patients. PMID- 17272998 TI - Effect of intravenous application of esomeprazole 40 mg versus pantoprazole 40 mg on 24-hour intragastric pH in healthy adults. AB - BACKGROUND: It has been demonstrated that therapy with proton pump inhibitors reduces recurrence of bleeding following initial endoscopic treatment of bleeding peptic ulcers. AIM: This study compared the effects of esomeprazole 40 mg and pantoprazole 40 mg on intragastric acid control. Both substances were administered intravenously as 15-min infusion and as bolus injection. METHODS: Healthy men and women volunteers were enrolled in this single-center, open, randomized, three-way crossover study. After administration of esomeprazole 40 mg and pantoprazole 40 mg intravenously as 15-min infusion, and pantoprazole 40 mg intravenously as bolus injection, continuous 24-h intragastric pH monitoring was carried out. RESULTS: pH data were available for 21 Helicobacter pylori-negative and seven H. pylori-positive volunteers. In H. pylori-negative volunteers, esomeprazole 40 mg intravenously resulted in 11.8 h with an intragastric pH>4 compared with 5.6 h for pantoprazole 40 mg intravenously as infusion (P<0.0001), and 7.2 h for pantoprazole 40 mg intravenously as bolus injection (P<0.001). During the first 6 h of administration, the corresponding values were 3.4, 1.1 (P<0.000001), and 2.1 h (P<0.001), respectively. CONCLUSIONS: In H. pylori negative patients, a single dose of esomeprazole 40 mg intravenously provides an intragastric acid control that is faster and more pronounced than administration of pantoprazole 40 mg intravenously. PMID- 17272999 TI - Inducible nitric oxide synthase gene promoter polymorphism is associated with increased gastric mRNA expression of inducible nitric oxide synthase and increased risk of gastric carcinoma. AB - BACKGROUND AND AIMS: Stimulation of inducible nitric oxide synthase gene expression by Helicobacter pylori, with subsequent overproduction of nitric oxide, has been implicated in gastric carcinogenesis. We investigated whether inducible nitric oxide synthase promoter gene polymorphisms are associated with (a) inducible nitric oxide synthase mRNA expression in the gastric mucosa, and (b) the risk of gastric carcinoma. MATERIALS AND METHODS: The relationship between gastric inducible nitric oxide synthase mRNA expression and inducible nitric oxide synthase promoter polymorphisms (CCTTT repeat polymorphism and -2445 C-->G SNP) was examined in 74 H. pylori-infected patients with gastric cancer, peptic ulcer, or functional dyspepsia. In a case-control study the prevalence of the polymorphisms was examined in H. pylori-infected gastric carcinomas (n=77) and noncancerous controls (n=154). RESULTS: Inducible nitric oxide synthase mRNA levels were significantly higher in long CCTTT repeat (either allele>11) carriers than in short ones (P=0.015). Multivariate regression analysis showed that inducible nitric oxide synthase mRNA expression was significantly linked to long CCTTT repeat and gastric cancer (P=0.026), but not to -2445 C-->G SNP and other parameters. The case-control study showed that long CCTTT repeat carriers had an increased risk of gastric cancer with an odds ratio of 2.0 (P=0.021). -2445 C-->G SNP was not associated with the risk. CONCLUSIONS: Helicobacter pylori induces higher inducible nitric oxide synthase mRNA expression in carriers of long CCTTT repeats of inducible nitric oxide synthase promoter, and this polymorphism is associated with an increased risk of gastric carcinoma. PMID- 17273000 TI - Mannose-binding lectin deficiency does not increase the prevalence of Helicobacter pylori seropositivity. AB - BACKGROUND: Mannose-binding lectin is an immune molecule that can bind to pathogens and initiate the complement cascade. In certain clinical situations, often characterized by immune compromise, mannose-binding lectin deficiency can increase the risk of infectious complications. Helicobacter pylori is one of the most common human infections and can bind mannose-binding lectin. Therefore, we examined whether mannose-binding lectin status influences the prevalence of H. pylori infection. METHODS: Two distinct populations were targeted. The first consisted of 166 volunteer blood donors, the second included 108 peripheral blood stem cell donors. All were tested for serological evidence of H. pylori infection, and had their mannose-binding lectin status characterized by genotyping, and quantification of mannose-binding lectin mannan-binding level and C4-deposition function in plasma. RESULTS: H. pylori positive blood donors had higher blood mannose-binding lectin levels, as measured by C4 deposition (median 0.67 vs. 0.40, P=0.009, hazard ratio 2.82, 95% confidence interval 1.29-6.19) and mannan-binding assays (median 1.83 vs. 1.26, P=0.02, hazard ratio 1.28, 95% confidence interval 1.03-1.59). A trend was also found between the presence of an MBL2 coding mutation and a reduced prevalence of H. pylori. No significant associations were found in the second population. CONCLUSIONS: Mannose-binding lectin deficiency does not increase the risk of H. pylori infection. The finding in one population that greater mannose-binding lectin activity might predispose to infection, suggests that this study should be repeated in other large cohorts of normal subjects. PMID- 17273001 TI - Assessment of intestinal vascular malformations in patients with hereditary hemorrhagic teleangiectasia and anemia. AB - INTRODUCTION: Hereditary hemorrhagic teleangiectasia (HHT) is an autosomal dominant disorder with mucocutaneous teleangiectasia and visceral arteriovenous malformations. Mutations of endoglin and Activin A receptor like kinase-1 have different phenotypes, HHT1 and HHT2, respectively. The gastrointestinal tract is frequently affected, but limited information is available on the relationship with genotype. AIM: To determine whether different genotypes have different phenotypes with respect to intestinal teleangiectasia. METHODS: HHT patients, referred for anemia, underwent videocapsule endoscopy. Chart review was performed for information on genotype and HHT manifestations. RESULTS: Twenty-five patients were analyzed (men/women 13/9, mean age 49+/-15 years.), 14 HHT1, eight HHT2 and three without known mutation. Epistaxis occurred in 96% of patients. Gastroduodenoscopy revealed teleangiectasia in 7/12 (58%) HHT1 and 3/8 (38%) HHT2 patients. Videocapsule endoscopy found teleangiectasia in all HHT1 and 5/8 (63%) HHT2 patients. In 9/14 HHT1 patients, teleangiectasia were large. Teleangiectasia in the colon was restricted to 6/11 (55%) HHT1 patients. Hepatic arteriovenous malformations were present in 1/7 HHT1 and 5/6 HHT2 patients. CONCLUSION: Large teleangiectasia in small intestine and colon appear to occur predominantly in HHT1. Hepatic arteriovenous malformations are mainly found in HHT2. In HHT patients with unexplained anemia, videocapsule endoscopy should be considered to determine the size and extent of teleangiectasia and exclude other abnormalities. PMID- 17273002 TI - Acute paraplegia after the initiation of anti-tumour necrosis factor-alpha therapy for Crohn's disease. AB - Therapies aimed at inhibiting tumour necrosis factor are currently successfully administered to an increasing number of patients with autoimmune diseases. Infliximab has been approved to induce and maintain remission in Crohn's disease and fistulizing Crohn's disease. We report a case of acute-onset flaccid paraplegia after the initiation of anti-tumour necrosis factor therapy (infliximab) for Crohn's disease. Neuroimaging findings revealed an extensive longitudinal myelopathy. Two months later, no abnormal signal intensity was observed in the spinal cord and after 4 months, the patient presented improvement of motor function. A possible correlation between anti-tumour necrosis factor therapy and acute myelitis is discussed. This case highlights that patients developing new neurological symptoms while on anti-tumour necrosis factor medication should be monitored closely. PMID- 17273003 TI - A diagnosis of Fabry gastrointestinal disease by chance: a case report. AB - Fabry disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase A. This determines an accumulation of globotriaosylceramide within lysosomes. The clinical picture is highly variable and depends on cellular storage deposition. Renal, cardiac and nervous system are the most frequent organs involved. Gastrointestinal involvement is also present, associated with other clinical signs of Fabry disease and sometimes can be a prominent clinical manifestation. We describe a Fabry disease case in which gastrointestinal involvement was the first and the only clinical sign of Fabry disease and a diagnosis of Fabry disease was made by chance during a family screening. Enzyme replacement therapy was started and after 3 months, there was a complete disappearance of signs. PMID- 17273004 TI - Mirizzi syndrome complicating an anomalous biliary tract: a novel cause of a hugely elevated CA19-9. AB - A 71-year-old man presented with painful obstructive jaundice, weight loss and an elevated CA19-9 (>16,000 U/ml) (normal levels <39 U/ml). Imaging showed a hilar mass. After biliary stenting, the CA19-9 returned to normal. At surgery, biliary obstruction owing to a gallstone (Type II Mirizzi) was found to be complicating a congenital biliary tract anomaly. The obstructing stone was removed and the anomalous biliary tract reconstructed with a Roux-en-y loop, and the patient made an uneventful recovery and remained normal over a 2-year follow-up. A Type II Mirizzi with a biliary tract anomaly is an undocumented cause of an elevated CA19 9. The possibility of benign disease must be considered even with very high levels of the cancer marker CA19-9 or the opportunity for curative surgery may be missed. PMID- 17273005 TI - Diet habits, alcohol drinking, tobacco smoking, green tea drinking, and the risk of esophageal squamous cell carcinoma in the Chinese population. AB - OBJECTIVE: This study aims to investigate the risk of esophageal squamous cell carcinoma in relation to exogenous factors in a rural area of China with a high incidence of esophageal squamous cell carcinoma. METHODS: A population-based case control study was conducted in Yangzhong County, Jiangsu Province, China, with 355 histologically confirmed esophageal squamous cell carcinoma cases recruited between 1 January 2004 and 28 February 2006 and 408 controls matched by sex and age, randomly selected from the local population. RESULTS: Stratified logistic regression analysis by sex revealed that hot-temperature food items, pork braised in brown sauce and old stocked rice intake could increase the risk of esophageal squamous cell carcinoma with odds ratio of 2.127 (95% confidence interval: 1.394 3.245), 2.059 (95% confidence interval: 1.417-2.993) and 9.059 (95% confidence interval: 5.930-13.840), respectively, in men and 3.048 (95% confidence interval: 1.733-5.364), 1.914 (95% confidence interval: 1.159-3.162) and 14.532 (95% confidence interval: 7.816-27.019), respectively, in women, whereas diet high in salt and chili, tobacco smoking and alcohol drinking only showed possible risk effects in men with odds ratio 2.338 (95% confidence interval: 1.568-3.485), 3.378 (95% confidence interval: 2.117-5.389), 1.976 (95% confidence interval: 1.337-2.921) and 2.197 (95% confidence interval: 1.510-3.195), respectively. Green tea drinking showed a protective effect in women (odds ratio=0.257; 95% confidence interval: 0.070-0.941). CONCLUSIONS: Findings from this study provided evidence that dietary habits, tobacco-smoking and alcohol drinking contribute to the etiology of esophageal squamous cell carcinoma. A healthy dietary habit, with smoking cessation and alcohol controlling is of a great importance in the prevention of esophageal cancer. PMID- 17273006 TI - Endoscopic resection of benign very low-risk gastric gastrointestinal stromal tumors. Is it enough? AB - Great ongoing debate still exists over the definition, diagnosis and treatment of gastrointestinal stromal tumour especially for small gastric submucosal tumours. Simple endoscopic biopsy is not sufficient to determine their biological behaviour and their complete excision is necessary. We report the case of a 65 year-old woman, who was kept under observation after previously operated breast cancer, with a casual computed tomography-diagnosed submucosal gastric lesion. Endoscopy and endoscopic ultrasound confirmed a submucosal mass of 2-3 cm in diameter. An endoscopic resection was performed and the mass was integral at pathologic examination. It confirmed the stromal origin with a mitotic index of 1 (5/50 high power field). No more treatment was carried out because it was classified as a very low risk gastrointestinal stromal tumour according to Fletcher's classification. After 34 months follow-up, the patient is disease free and we believe that endoscopic treatment is sufficient and recommended for mainly intragastric growing gastrointestinal stromal tumour with a diameter of less than 3 cm. PMID- 17273007 TI - Sulphasalazine-induced hypersensitivity syndrome: a relapsing disorder and the role of human herpes virus-6. PMID- 17273008 TI - Liver enzyme levels in relation to a common polymorphism in the CD14 promoter gene. PMID- 17273009 TI - The value of certification. PMID- 17273010 TI - The effect of postoperative symptom experience, and personality and psychosocial factors on depression among postgastrectomy patients in Japan. AB - Depression, the most common affective disorder in cancer, has a major impact on quality of life. Various risk factors may interact and affect a cancer patient's depressive state. The purpose of this study was to examine the relationships between depression and postoperative symptom experience, personality, and psychosocial factors in Japanese gastrectomy patients. Causal relationships of these variables were also estimated. Eighty-two Japanese gastrectomy patients (M age = 63.63 years, SD = 10.21; men = 50, women = 32), who had been discharged within the last 3 years with no indication of cancer recurrence, participated in the study. Results showed significant correlations between depression and age, time-since-discharge, postoperative symptom experience, frequency of symptoms, self-esteem, and emotional support. Path analysis showed sufficient goodness of fit index (GFI = 0.993, AGFI = 0.963). Interpersonal dependency, emotional support, and marital status showed a direct effect on self-esteem, which, along with postoperative symptom experience, had a direct effect on depression. Findings provide a useful reference point for further understanding the mental health condition of postgastrectomy patients. PMID- 17273011 TI - Florence Nightingale: Appreciating our legacy, envisioning our future. AB - "If a man does not keep pace with his companions, perhaps it is because he hears a different drummer. Let him step to the music that he hears, however measured or far away." This quote is attributed to Henry David Thoreau, (Walden, 1854) not Florence Nightingale, but it certainly can describe Florence, particularly in early life. Florence, you can say, "had it all": wealth, education, a doting extended family, and a life of leisure, which included the opportunity to travel anywhere in the world. Even her name was given because she was born in Florence, Italy, during her parents' 3-year honeymoon tour of Europe. But inside Florence, "the different drummer" quietly but steadily beat, and her life was compelled to seek until she could find or, in her case, create the music she heard. After years of searching, Florence determined that "nursing," a practice every woman engaged in, was not simply a matter of kindness and care, but rather a body of knowledge, an art and a science. She never lost sight of her goal that nursing should become a profession in its own right, and not a branch of medicine. Nursing at that time was reserved for nuns in Germany, Ireland, and France, or for family and friends caring for relatives who were ill. Florence felt nursing was her "calling" and her mission. Once she discovered nursing, she pursued it for more than 50 years until the last moment of her life. Her dedication has a good deal to do with how and why we are nursing today. PMID- 17273012 TI - Obstructive sleep apnea and sedation in the endoscopy suite. AB - Patients with obstructive sleep apnea are at risk of mortality and morbidity related to the administration of sedatives, anesthetics, and opioids. Commonly employed sedatives and analgesics promote pharyngeal collapse and alter normal respiratory responses to obstruction and apnea. Literature concerning patients with obstructive sleep apnea undergoing moderate and deep sedation in the endoscopy suite is lacking. The purpose of this article is to provide the reader with a review of normal airway patency, the effects of obstructive sleep apnea on airway patency, and the impact that analgesics and sedatives may impart on the airway of patients with obstructive sleep apnea. The goal of this article is to increase awareness, stimulate discussions within the gastroenterological community, and encourage research regarding sedation in this at-risk population. PMID- 17273013 TI - Aromatherapy and reducing preprocedural anxiety: A controlled prospective study. AB - The purpose of this study was to evaluate the use of aromatherapy to reduce anxiety prior to a scheduled colonoscopy or esophagogastroduodenoscopy. A controlled, prospective study was done on a convenience sample of 118 patients. The "state" component of the State Trait Anxiety Inventory (STAI) was used to evaluate patients' anxiety levels pre- and postaromatherapy. The control group was given an inert oil (placebo) for inhalation, and the experimental group was given the essential oil, lavender, for inhalation. The STAI state anxiety raw score revealed that patients were at the 99th (women) and 96th (men) percentiles for anxiety. The intervention group and the control group had similar levels of state anxiety prior to the beginning of the study (t[116] = .47, p = .64). There was no difference in state anxiety levels between pre- and postplacebo inhalation in the control group (t[112] = .48, p = .63). There was no statistical difference in state anxiety levels between pre- and postlavender inhalation in the experimental group (t[120] = .73, p = .47). Although this study did not show aromatherapy to be effective based on statistical analysis, patients did generally report the lavender scent to be pleasant. Lavender is an inexpensive and popular technique for relaxation that can be offered to patients as an opportunity to promote preprocedural stress reduction in a hospital setting. PMID- 17273014 TI - Pregnancy testing. PMID- 17273015 TI - Colorectal cancer in young patients. PMID- 17273016 TI - Percutaneous feeding tube placement and severe anorexia nervosa. PMID- 17273017 TI - Framing the future. PMID- 17273018 TI - Personal reflections about the theory-research-practice connection. PMID- 17273019 TI - New JCAHO nursing standards: will you be at the table? PMID- 17273021 TI - Barriers to research use. PMID- 17273022 TI - The American Organization of Nurse Executives' Guiding Principles and American Association of Colleges of Nursing's Clinical Nurse Leader: a lesson in synergy. PMID- 17273023 TI - The desired future of nursing doesn't just happen--engaged nurses create it. PMID- 17273024 TI - Hardwiring evidence-based practice in a community hospital setting. PMID- 17273025 TI - Nurse-physician work relations and role expectations. PMID- 17273026 TI - Classic, new, and not-so-new readings for nurse executives. PMID- 17273027 TI - Positive organizational scholarship. Interview by Karen S. Hill. PMID- 17273028 TI - An intervention to enhance nursing staff teamwork and engagement. AB - Numerous studies have concluded that work group teamwork leads to higher staff job satisfaction, increased patient safety, improved quality of care, and greater patient satisfaction. Although there have been studies on the impact of multidisciplinary teamwork in healthcare, the teamwork among nursing staff on a patient care unit has received very little attention from researchers. In this study, an intervention to enhance teamwork and staff engagement was tested on a medical unit in an acute care hospital. The results showed that the intervention resulted in a significantly lower patient fall rate, staff ratings of improved teamwork on the unit, and lower staff turnover and vacancy rates. Patient satisfaction ratings approached, but did not reach, statistical significance. PMID- 17273029 TI - Development of a leadership competency model. AB - BACKGROUND: Although research findings support that the nurse manager has a pivotal role in influencing all aspects of the nursing environment, recruiting talented staff into these nursing leadership positions has become increasingly more difficult. There is a need to better understand the competencies needed by contemporary nurse managers and the challenges in the role. OBJECTIVE: The purpose of this research was to explore the viewpoints of 120 nurse manager study participants on the contemporary nurse manager role and to gain perspective on the critical leadership skills and competencies to build a nursing leadership competency model. DESIGN: A grounded theory methodology was used in this study to capture the perspectives of the nurse managers interviewed about their role. RESULTS: Six competency categories emerged from the research findings to form a nursing leadership competency model. Two major themes identified from the data included the nurse manager role as a career choice and the stressors and challenges in the role. CONCLUSION: The results of this study led to the design of a nursing leadership competency model and confirmed that there is a need to formally develop and mentor our next generation of nurse leaders. PMID- 17273031 TI - Current practice in the management of acute/unstable slipped capital femoral epiphyses in the United Kingdom and the Netherlands: results of a survey of the membership of the British Society of Children's Orthopaedic Surgery and the Werkgroep Kinder Orthopaedie. AB - A questionnaire was sent to all members of the British Society for Children's Orthopaedic Surgery and the Werkgroep Kinder Orthopaedie to identify points of agreement/disagreement on the management of the acute unstable slip of the upper femoral epiphysis and to compare these European results with those from a similar North American survey. Sixty-five per cent responded. Overall, both countries evaluated cases similarly and believed in their urgent management. Sixty-six per cent did not reposition the slip. Significant differences were observed in attitude towards single screw usage, prophylactic pinning and metalwork removal both between the two countries and in comparison with North America. PMID- 17273030 TI - Enhancing patient safety: improving the patient handoff process through appreciative inquiry. AB - Patient transfers from one care giver to another are an area of high safety consequence, as is evident by many studies and the Joint Commission on Accreditation of Healthcare Organization's Patient Safety Goals. The authors describe how one hospital made measurable improvements in a patient handoff process by using an unconventional approach to change called appreciative inquiry. Rather than identifying the root causes of ineffective handoffs, appreciative inquiry was used to engage staff in identifying and building on their most effective handoff experiences. PMID- 17273032 TI - Residual axial plane deformities after hip reconstruction for developmental dysplasia of the hip after walking age. AB - Children with developmental dysplasia of the hip after walking age can be treated with one-stage combined operations. In these procedures, complex deformity corrections at both frontal and axial planes are performed in the guidance of intraoperative stability tests. The reports about the results of these procedures focus on frontal plane assessments but neglect to assess axial plane corrections. We aimed to find out whether hips with unilateral developmental dysplasia of the hip, treated by one-stage combined procedures after walking age and which had good frontal plane containment at the last follow-up, had any axial plane deformities. Twenty-one patients were included in this study according to our described criteria. Mean age at the operation time was 38.04 months (range: 20-86 months), mean follow-up time was 55.54 months (range: 24-117 months) and mean age at latest follow-up was 93.46 months (range: 52-150 months). Femoral anteversions, acetabular anteversions and acetabular sector angles were measured bilaterally in the computed tomography examination. Operated hip measurements were compared with the contralateral hips. One-way variance analysis was used for statistical analysis. Femoral anteversion, acetabular anteversion and posterior acetabular sector angle values of the operated hips were found to be statistically lower than those of the contralateral hips. Our findings suggest that using the intraoperative stability test alone for planning osteotomies may lead to unsuitable femoral head coverage in axial plane although successful frontal plane containment can be obtained. We believe that strict preoperative planning that can be accomplished by a preoperative computed tomography examination should be performed in order to decide innominate osteotomy type and correction amounts. PMID- 17273033 TI - Rare peripheral femoral nerve neuropathy in children. AB - Peripheral neuropathy of the femoral nerve is extremely rare. In the literature, we found descriptions of only 50 similar patients, mainly as a complication of coagulopathies, and none of intrapelvic tumors. Three children with a rare peripheral neuropathy of the femoral nerve as a complication of extraperitoneal pelvic masses are described in this report. In all three, the neuropathy was caused by stretching of the femoral nerve over a huge intrapelvic mass. None was related to coagulopathy. After removal of the masses, full recovery from the neurological symptoms was observed in two children and the recovery of the patient with Ewing's sarcoma is satisfying, at the 2-year follow-up and at the time of writing. As early surgical debulking of the mass was a good influence on the recovery of the nerve paresis, we believe that is imperative in the treatment process. Medical staff should be aware that a serious illness can lie behind peripheral femoral nerve neuropathy. PMID- 17273035 TI - Treatment of idiopathic clubfoot using the Ponseti method: minimum 2-year follow up. AB - One hundred and thirty-seven idiopathic clubfeet were treated by the Ponseti technique and followed for at least 2 years. Nine feet (7%) were not corrected with initial casting and required early surgery. Recurrence after correction was related to compliance with bracing. At latest follow-up, two-thirds of those noncompliant with brace had recurrences with one-third of these recurrences requiring more extensive surgery than Achilles tenotomy and anterior tibial tendon transfer while only 14% of those compliant with brace had recurrences with none requiring more than Achilles tenotomy and anterior tibial tendon transfer. Early failures and recurrences constituted about 20% of our 137 feet by 2 years of follow-up. When the Ponseti method was fully followed, including initial casting, compliance with brace and treatment of recurrences by recasting, Achilles tenotomy and/or anterior tibial tendon transfer, our success rate was 93%. PMID- 17273034 TI - Operative treatment of bilateral hip dislocations in a child with metatropic dysplasia. AB - We present a case of bilateral hip dislocations with metatropic dysplasia. Radiographic features such as narrow thorax, dense wafer vertebral bodies, narrowing interpedicular distances, kyphoscoliosis, crescent-shaped iliac wings, dumbbell-shaped tubular bones, and inferiorly directing lesser trochanter conform to the findings of metatropic dysplasia. Hip dislocations were misdiagnosed by ultrasonographic and radiographic hip screening, owing to the severely deformed femoral heads and acetabulums. The diagnosis of hip dislocations became possible by magnetic resonance imaging. The bilateral hip dislocation was reduced by open reduction of the hip joints and femoral derotation varus osteotomies. PMID- 17273036 TI - Accessory soleus muscle in clubfoot deformity: a report in four feet. AB - The commonest presentation of accessory soleus muscle is a swelling at the posteromedial aspect of the ankle in adolescents or young adults. Accessory soleus is rarely encountered in children undergoing surgical release for congenital clubfoot, and only a few isolated reports are available in the literature. The purpose of this study is to heighten awareness about the role of accessory soleus muscle in clubfoot deformity. Four cases of accessory soleus muscle in patients undergoing surgical release for clubfoot deformity are reported here in which, a distinct anomalous muscle deep to the tendoachilles was identified. Hindfoot varus and equinus persisted in each of these cases despite an adequate posteromedial soft tissue release, which could be corrected only on tenotomizing the tendon of the accessory soleus muscle at its insertion. An awareness about the accessory soleus muscle is important, particularly when non operative methods of clubfoot management with tendoachilles tenotomy or limited surgery are employed. Failure to recognize this muscle if present in patients with congenital clubfoot may lead to persistent hindfoot deformity. A high index of suspicion should be maintained in cases in which hindfoot deformity persists despite an otherwise adequate soft tissue correction. PMID- 17273038 TI - Acute correction of proximal tibial deformities in adolescents using Ilizarov external fixator: focal-dome versus straight-cut osteotomy. AB - Straight-cut osteotomy was compared with focal-dome osteotomy in two similar groups of patients with proximal tibial deformities. Acute correction of deformity was carried out for 27 patients with a total of 36 bone segments. Ilizarov external fixator was used in all cases. No significant difference was found between the two groups in terms of bone healing, external fixation time and stability of osteotomy. The follow-up ranged from 24 to 63 months. In this study, the focal-dome osteotomy was not found to be superior to straight-cut osteotomy, which is simpler to perform and more versatile for deformity correction. PMID- 17273039 TI - The Haas procedure for the treatment of tibial torsional deformities. AB - This study reviews our 13-year experience with Haas's multiple-longitudinal osteotomy technique for correction of tibial torsion in children. In this procedure, multiple-longitudinal bi-cortical osteotomies are made parallel in the proximal tibia. The deformity is corrected by applying moderate force in the desired plane. Fixation is achieved either with a long cast or with 'pins-in plaster'. Forty-six osteotomies were performed in 30 children. In all, there were 35 internal tibial torsion deformities and 11 external tibial torsion deformities. Twenty-one (46%) deformities were associated with spastic cerebral palsy and 15 (33%) were associated with clubfeet. Ten (22%) deformities had no underlying musculoskeletal conditions. Thigh-foot angles were corrected by a mean of 24 degrees for internal tibial torsion and -28 degrees for external tibial torsion. Average anesthesia time for unilateral cases was 46 min. No neurologic or infectious complications, postoperative fractures or physeal damage occurred. There was one case of delayed union and one case of postoperative antecurvatum deformity. All five cases of postoperative recurrent deformities were associated with cerebral palsy. This technique is a simple, safe and efficient method for correcting tibial torsional deformities in both healthy children and those with underlying conditions. It allows accurate alignment of different deformities with a uniform osteotomy technique, which preserves bone continuity and provides inherent stability, thus avoiding the use of internal fixation. PMID- 17273037 TI - Infantile digital fibromatosis. AB - The authors report a case series on four patients with infantile digital fibromatosis located on pedal digits. Surgical excision was performed in all cases, with no evidence of recurrence. It is a rare form of juvenile fibromatosis, which presents on the fingers and toes of infants and children. Conservative treatment is recommended by authors owing to the benign nature of the lesion and its tendency to regress, and reports of recurrence after surgical intervention. We believe that surgical excision of lesions in this condition, however, remains an appropriate recommendation for the management of this rare entity. PMID- 17273041 TI - Nancy nail versus intramedullary-wire fixation of paediatric forearm fractures. AB - Intramedullary nailing provides effective fracture fixation with satisfactory functional outcome without the risks associated with plating. Unfortunately, elastic stable intramedullary nailing devices are not always available in every hospital. We have examined the outcome of 23 children who underwent intramedullary fracture fixation of one or both forearm diaphyseal fractures in our department. We have compared the outcome of intramedullary Nancy nailing with the use of standard, available K-wires to achieve intramedullary fixation. We have assessed, over a 12-month period, rates of union (100% in both groups), function of the forearm and complication rates. We have found no significant increase in the rates or severity of complications when using K-wires compared with Nancy nails. Both groups had equal excellent functional outcome. We advocate that if elastic stable intramedullary nailing devices are unavailable, a K-wire can be used to achieve three-point compression of a paediatric forearm diaphyseal fracture. PMID- 17273040 TI - High recurrence after calf lengthening with the Ilizarov apparatus for treatment of spastic equinus foot deformity. AB - Both gastrocnemius recession and Achilles tendon lengthening lead to scarring in the calf and have high reported recurrence rates when performed under the age of 8 years. Triceps surae lengthening by external fixation seemed to be a valuable alternative. Twelve calf lengthenings have been performed with an Ilizarov device with a mean correction of 27 degrees. No calcaneal gait was observed, but there was a slow continuous loss of dorsiflexion over the observation period. The Ilizarov technique has a higher recurrence rate than most operative procedures for calf lengthening, but carries virtually no risk in producing calcaneus. The technique cannot be recommended for routine clinical use and may only be an alternative for selected cases. PMID- 17273042 TI - Vascular complications of supracondylar humeral fractures in children. AB - The purpose of this study was to analyze the vascular complications of 24 children with supracondylar humeral fractures treated in two affiliated hospitals and to propose a management plan. Exploration and repair of the brachial artery were undertaken in 11 of the 24 cases in which the pulse did not resume following reduction of the fracture. The repaired vessels were found to be patent on follow up. Angiography was performed in six of the 24 cases and resulted in improved management in comparison with cases in which no angiography was performed. We believe that intra-operative angiography and vascular repair are indicated in most cases in which a palpable pulse does not resume after fracture reduction. PMID- 17273043 TI - Elbow range of motion and clinical carrying angle in a healthy pediatric population. AB - Many conditions including trauma can affect the range of motion and carrying angle of the elbow in children. The method employed was cross-sectional clinical measurement of 600 elbows (300 patients) range of motion and carrying angle in normal children. We found significant increases in range of motion and carrying angle with age (P<0.01) and significantly increased range of motion and carrying angle in females as compared with males (P<0.01). In conclusion, elbow joint range of motion and carrying angle increase with age. This is the first cross sectional analysis of range of motion and carrying angle to our knowledge in the pediatric population. Increased elbow extension may contribute to the increased carrying angle seen in females compared with males. PMID- 17273044 TI - Congenital pseudarthrosis of the ulna. AB - We report a case of congenital pseudarthrosis of the ulna along with generalized neurofibromatosis (type I). The patient had a good clinical outcome after single bone forearm reconstruction. In the setting of radial head dislocation following long-standing congenital pseudarthrosis of the ulna, single-bone forearm reconstruction is a viable option. It prevents the loss of hand function by the effective shortening of flexor tendons and spares movements of the humeroulnar and radiocarpal joints. PMID- 17273045 TI - Primary pyomyositis in children: a retrospective analysis of 11 cases. AB - This study was undertaken to review our approach to diagnosis and treatment in a series of 11 patients (mean age 8.2 years) with primary pyomyositis, who had neither an underlying disease nor a compromised immune system. Nine of the children had positive blood cultures, Staphylococcus aureus (eight) and Streptococcus group A (one). The sites of infection were iliopsoas (four), obturator (two), hip adductors (two), levator scapula (one), thoracolumbar paraspinal (one) and gastrocnemius (one) muscles. Antibiotic treatment was initially intravenous, followed by oral administration. Of five patients with evidence of abscess formation, three underwent percutaneous drainage, whereas two required open surgical drainage. The infection resolved completely without any sequela in 10 children. One patient who developed acute compartment syndrome showed late signs of osteonecrosis of the tibial shaft segment. PMID- 17273046 TI - Bursal osteochondromatosis overlaying an osteochondroma in the immature skeleton. AB - A rare case of bursal osteochondromatosis overlying an osteochondroma located at the proximal third of the left tibia in a 10-year-old boy is described. The treatment was operative by marginal resection of the affected bursa and marginal en bloc resection of the osteochondroma. The patient remains symptom and complication free 8 years postoperatively with no sign of recurrence of both lesions. This is the first reported case of a bursal osteochondromatosis overlying an osteochondroma in a developing skeleton, thus rendering this type of lesion one among the possible differential diagnoses that should be considered when dealing with relative diagnostic dilemmas in immature patients. PMID- 17273047 TI - Should human error be a crime? PMID- 17273057 TI - Boosting insulin safety. PMID- 17273058 TI - Measuring wounds. PMID- 17273062 TI - How do I respond to a chronically ill patient who's suicidal? PMID- 17273063 TI - New pain management options: delivery systems and techniques. PMID- 17273064 TI - The truth about scabies. PMID- 17273079 TI - How to protect a patient with aortic aneurysm. AB - Learn how to recognize and respond to the danger signs and act immediately to help save his life. Trouble is looming when the largest artery in the body develops a bulge. According to the Society for Vascular Surgery, each year approximately 200,000 people in the United States are diagnosed with aortic aneurysm - a bulge or ballooning in the artery that leads from the heart. About 15,000 of these aneurysms are severe enough to rupture, creating an urgent situation with a high risk of death. Read on to learn how to protect a patient with a suspected or known aortic aneurysm. PMID- 17273081 TI - Fried eggs and nursing. PMID- 17273082 TI - Focusing on eye emergencies. AB - Learn what to do when quick action can prevent vision loss. PMID- 17273083 TI - On the cutting edge of robotic surgery. AB - Joysticks meet scalpels in a new computer-enhanced surgery system. A new robotic surgical system is taking laparoscopic surgery to new horizons. With the potential for greater surgical precision, shorter hospital stays, and better patient outcomes, this minimally invasive surgical technique offers an exciting new option for many patients undergoing various surgical procedures. Read on to learn more about robotic surgery, including your role in patient care. PMID- 17273086 TI - Getting the point about fibromyalgia. AB - Invisible and incurable, this disorder can wreak havoc with your patient's life. Find out how to get her back on track. Fibromyalgia, a complex, chronic disorder of pain processing, is thought to be the most common cause of generalized musculoskeletal pain in women ages 20 to 55. This disorder, which affects the muscles, ligaments, and tendons, occurs in 3 to 6 million Americans, mostly women. Some patients are affected only mildly, but up to 30% have symptoms that seriously impair their quality of life. PMID- 17273084 TI - New drugs 07, part I. AB - In this article, you'll learn about 13 new drugs, including: insulin glulisine and insulin detemir, both human insulin analogues; ranolazine, the first drug approved to treat chronic angina in more than a decade; conivaptan HCl, the first drug approved to treat hyponatremia in patients with normal fluid balance. Unless otherwise specified, the information in the following summaries applies to adults, not children. Consult the package insert for information about each drug's safety during pregnancy and breast-feeding. Also consult the package insert, a pharmacist, or a comprehensive drug reference for more details on precautions, drug interactions, and adverse reactions for all these drugs. PMID- 17273092 TI - Managing hyperemesis gravidarum. PMID- 17273093 TI - Screening for abuse and neglect. PMID- 17273094 TI - Screening for microalbuminuria. PMID- 17273096 TI - Intussusception. PMID- 17273097 TI - Energizing the orthopedic nurse of the future. PMID- 17273099 TI - Soft tissue sarcoma: An overview. AB - Malignancy of soft tissue, referred to as sarcomas, are some of the rarest tumors in medicine. These tumors account for approximately 1% of all diagnosed malignancies. Diagnosis of soft tissue sarcoma (STS) is a complex process that includes history and physical examination of patient, diagnostic imaging studies, and biopsy when indicated. All clinicians should be able to identify the unique characteristics of malignant soft tissue tumors and assist patients with obtaining care from a specialist in the treatment of STS. Evidence-based medicine has shown that the critical difference in treating STSs is a multidisciplinary approach. PMID- 17273101 TI - Patient Safety and Quality Improvement Act of 2005. AB - All medical personnel are concerned with patient safety. Nurses are well positioned, with their constant interaction with patients, to observe for errors and to analyze the systems that led to those errors. The Patient Safety and Information Act, legislation passed in 2005, encourages voluntary reporting of errors without fear of retribution. Data, stripped of identifiers, will be maintained by public or private entities. The analysis of the information collected will be used to improve medical systems and practice. PMID- 17273103 TI - Scoliosis, superior mesenteric artery syndrome, and adolescents. AB - Adolescent idiopathic scoliosis is defined as a lateral curvature of the spine that can occur in any region of the spinal column. For curves that require surgical correction, spinal fusion is the surgical treatment, and superior mesenteric artery syndrome is a possible complication. Risk factors for superior mesenteric artery syndrome include a small aorta-superior mesenteric artery angle, spinal lengthening, and an asthenic habitus. Asthenic habitus may be due to natural build, peptic ulcer disease, or anorexia, especially among adolescent females. Research regarding adolescent idiopathic scoliosis and superior mesenteric artery syndrome is warranted to identify if some adolescents are more likely to develop superior mesenteric artery syndrome. The advanced practice nurse can identify which adolescents may develop superior mesenteric artery syndrome and provide safe care to avoid this complication. PMID- 17273106 TI - Taking the mystery out of research: Box and whisker plots: Displaying mean, interquartile range, and range. PMID- 17273105 TI - Osteoporosis knowledge and information needs in healthcare professionals caring for patients with fragility fractures. AB - PURPOSE: To evaluate osteoporosis knowledge and learning needs in healthcare professionals working with patients who have experienced or are at risk of fracture. SETTING: Multisite teaching hospital, Hamilton, Ontario. SAMPLE: Healthcare professionals working in the fracture clinics, orthopaedics, rehabilitation, and nuclear medicine department. METHOD: Completion of an Osteoporosis Knowledge Questionnaire and questions about learning needs and preferences. RESULTS: The major areas of knowledge deficit in this study were with topics related to health promotion and management specific to calcium needs and medications. CONCLUSIONS: The range of scores on the Osteoporosis Knowledge Questionnaire and the low scores on key questions suggest that there are opportunities to increase osteoporosis knowledge across a broad spectrum of healthcare providers. PMID- 17273107 TI - Radiology nursing. AB - Radiology nursing is a relatively new field in which nurses can use multiple skills in caring for adult and pediatric patients. The authors present an overview of the role nurses play in interventional radiology, nuclear medicine, ultrasound, magnetic resonance imaging, computed tomography, and mammography. In addition, information about the professional affiliations and certification in the American Radiological Nurses Association is provided. PMID- 17273109 TI - Health literacy in geriatric patients: An integrative review of the literature. AB - The concept of health literacy is a recent addition to healthcare literature, appearing in the early to mid 1990s. Health literacy refers to individuals' ability to understand their healthcare issues and effectively care for themselves in the healthcare system. Individuals' health literacy abilities vary greatly and can be viewed on a continuum ranging from adequate to marginal to inadequate. Repeated research has demonstrated that older individuals, the geriatric patient population, are at risk of inadequate or marginal health literacy. This risk impacts health outcomes and cost for caring for the older people in our society who are the consumers of a large quantity of healthcare services. The demographic data from the research show that multiple factors influence an individual's health literacy. Besides age, individuals with less education, lower income, "blue collar" jobs, and poor health status (mental and physical) can be at risk of marginal or inadequate health literacy. Providing care to low health literacy patients is complicated by commercially prepared healthcare materials and presentations that are often written well above the average national literacy level. Studies in this review examine various approaches to healthcare education and provide viable options for educating those with low health literacy. This review stresses the importance of healthcare professionals identifying older individuals with marginal or inadequate health literacy and being able to provide education in an effective manner to this segment of the population. PMID- 17273111 TI - Direct observation approach for detecting medication errors and adverse drug events in a pediatric intensive care unit. AB - OBJECTIVE: To determine the incidence, type, and stage of occurrence of medication errors and potential and actual adverse drug events (ADEs) in a pediatric intensive care unit (ICU) using trained observers. The preventability and severity of ADEs and the system failures leading to medication error occurrence were also investigated. DESIGN: Prospective, direct observation study. SETTING: A 16-bed pediatric medical/surgical ICU at a tertiary care academic medical center. PATIENTS: One enrolled nurse caring for at least one pediatric ICU patient age <18 yrs was randomly chosen during each observation period. INTERVENTIONS: Observers would intervene only in the event that the medication error would cause substantial patient harm or discomfort. MEASUREMENTS AND MAIN RESULTS: Medication errors and potential and actual ADEs were identified throughout the entire medication use process. The 26 12-hr observation periods included 357 reviewed written orders and 263 observed doses. The study observers identified 58 incidents, which were subsequently classified by the evaluators according to clinical importance, severity, and preventability. Fifty-two of these incidents were considered medication errors; six incidents were determined to be nonpreventable ADEs. Of the 52 medication errors, 42 (81%) were considered clinically important. Potential ADEs comprised 35 (83%) of these important medication errors; the other seven (17%) were classified as actual, preventable ADEs. Overall, the actual and potential ADE rate occurred at 3.6 events and 9.8 events per 100 orders, respectively. CONCLUSIONS: Our medication error rate was similar to that of previous pediatric ICU studies that used the direct observation method for reporting but higher than the rates in previous studies using other detection techniques such as voluntary incident reporting. Periodic direct observation and other ongoing data collection methods such as voluntary incident reporting have the potential to be complementary approaches to medication error and ADE detection. PMID- 17273112 TI - Early elevation of plasma von Willebrand factor antigen in pediatric acute lung injury is associated with an increased risk of death and prolonged mechanical ventilation. AB - OBJECTIVE: Von Willebrand factor antigen (vWF-Ag) is a marker of pulmonary and systemic endothelial activation and injury. Adult studies indicate that patients with plasma vWF-Ag levels > or = 450% of control early in the course of acute lung injury (ALI) have an increased risk of death. The objective of this study was to evaluate whether vWF-Ag is elevated in the early phase of ALI in children and whether the magnitude of the increase was predictive of two important outcomes: mortality or duration of mechanical ventilation. DESIGN: Two-center, prospective observational study. SETTING: Two pediatric intensive care units: one in an academic university setting and one in a major community children's hospital. PATIENTS: After appropriate consent, plasma was collected from 48 pediatric patients on day 1 of ALI, 45 patients on day 2 of ALI, and four intubated controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean PaO2/FiO2 at the onset of ALI was 140 +/- 70, and mortality rate was 17%. vWF-Ag levels on day 1 of ALI were higher in patients compared with controls (287 +/- 183 vs. 87 +/- 84% of control [mean +/- SD], p < .05). Patients with vWF-Ag levels > or = 450% of control on day 1 of ALI had a markedly greater risk of death (odds ratio, 7.0; confidence interval, 1.31, 37.30; p < .05). Multivariate analysis revealed that elevated vWF-Ag level and either presence of multiple organ system failure or Pediatric Risk of Mortality III score independently predict increased risk of death. vWF-Ag levels on day 2 of ALI were significantly higher in patients who required prolonged mechanical ventilation (316 +/- 173 vs. 191 +/- 89% of control, p < .05). CONCLUSIONS: Early injury to the systemic and pulmonary endothelium, as measured by plasma vWF-Ag levels, is associated with an increased risk of death and prolonged mechanical ventilation in pediatric patients with ALI. PMID- 17273113 TI - Lung epithelial cell apoptosis during acute lung injury in infancy. AB - CONTEXT: Apoptosis of lung epithelial cells is implicated in the pathogenesis of acute lung injury. Most research on this subject has focused on adults. Very little is known about a potential interaction of this process with lung development in children. OBJECTIVE: To summarize the current literature on lung epithelial cell apoptosis and common causes of acute lung injury in infants and young children and to identify new areas of research. DESIGN: A Medline-based literature search. RESULTS AND CONCLUSIONS: Few studies have focused on lung epithelial cell apoptosis during common causes of acute lung injury in children. Nevertheless, the limited literature suggests that this may be an important mechanism during respiratory distress syndrome of infants and viral respiratory tract infection. Apoptosis is an essential process during lung development and maturation. Insufficient attention has been paid to potential consequences of this for the short- and long-term outcomes of acute lung injury. PMID- 17273114 TI - Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. AB - OBJECTIVE: To provide a general descriptive account of the end-organ effects of dexmedetomidine and to provide an evidence-based review of the literature regarding its use in infants and children. DATA SOURCE: A computerized bibliographic search of the literature regarding dexmedetomidine. MAIN RESULTS: The end-organ effects of dexmedetomidine have been well studied in animal and adult human models. Adverse cardiovascular effects include occasional episodes of bradycardia with rare reports of sinus pause or cardiac arrest. Hypotension has also been reported as well as hypertension, the latter thought to be due to peripheral alpha2B agonism with peripheral vasoconstriction. Although dexmedetomidine has no direct effects on myocardial function, decreased cardiac output may result from changes in heart rate or increases in afterload. There are somewhat conflicting reports in the literature regarding its effects on ventilatory function, with some studies (both human and animal) suggesting a mild degree of respiratory depression, decreased minute ventilation, and decreased response to CO2 challenge whereas others demonstrate no effect. The central nervous system effects include sedation and analgesia with prevention of recall and memory at higher doses. Dexmedetomidine may also provide some neuroprotective activity during periods of ischemia. Applications in infants and children have included sedation during mechanical ventilation, prevention of emergence agitation following general anesthesia, provision of procedural sedation, and the prevention of withdrawal following the prolonged administration of opioids and benzodiazepines. CONCLUSIONS: The literature contains reports of the use of dexmedetomidine in approximately 800 pediatric patients. Given its favorable sedative and anxiolytic properties combined with its limited effects on hemodynamic and respiratory function, there is growing interest in and reports of its use in the pediatric population in various clinical scenarios. PMID- 17273115 TI - Oxygen treatment restores energy status following experimental neonatal hypoxia ischemia. AB - OBJECTIVE: The purpose of this study was to determine whether oxygen treatment could attenuate the alterations in cerebral energy metabolism found in the brain following hypoxia-ischemia. DESIGN: Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 hrs of hypoxia (8% oxygen at 37 degrees C). The concentrations of high-energy phosphate compounds and glycolytic intermediates and the activity of Na+/K+-adenosine triphosphatase were measured at 4-72 hrs of recovery. Brain weight was used to determine the severity of the brain injury at 2 wks after insult. SETTING: Experimental setting. SUBJECTS: Rat pups. INTERVENTIONS: Pups were treated with 100% oxygen 1 hr after the insult at 2.5 atmospheres absolute (hyperbaric oxygen) or at normobaric pressure for a duration of 2 hrs. MEASUREMENTS AND MAIN RESULTS: During the initial period of recovery from hypoxia-ischemia, values of adenosine triphosphate and phosphocreatine remained at levels below normal, whereas the levels of glucose and other glycolytic intermediates were elevated. Hyperbaric oxygen and normobaric oxygen both attenuated brain injury, restored the levels of adenosine triphosphate and phosphocreatine, decreased the levels of the glycolytic intermediates, and increased the utilization of energy. CONCLUSIONS: These results suggest that oxygen treatment during the initial period of recovery from a hypoxia-ischemic insult is able to attenuate energy deficits in the brain, which ultimately leads to a reduction in brain injury. PMID- 17273116 TI - Hyperkalemia and cardiac arrest following succinylcholine administration in a 16 year-old boy with acute nonlymphoblastic leukemia and sepsis. AB - OBJECTIVES: To report a case of potentially lethal hyperkalemia related to succinylcholine administration. DESIGN: Case report. SETTING: A 13-bed pediatric intensive care unit in a tertiary level, university-based children's hospital. PATIENT: A 16-yr-old boy treated in the intensive care unit due to Klebsiella pneumoniae sepsis, which developed after chemotherapy for nonlymphoblastic leukemia. INTERVENTIONS: After admission to the intensive care unit, the patient required intubation (uneventful under ketamine and succinylcholine) and mechanical ventilation. On the 15th day of therapy, when his respiratory variables improved significantly, he was extubated. His cardiac rhythm, respiratory rate, arterial blood pressure, and hemoglobin oxygen saturation were continuously monitored. Several hours later, however, he required reintubation due to respiratory insufficiency. For intubation, precurarization with pancuronium, ketamine, propofol, and succinylcholine was used. MEASUREMENTS AND MAIN RESULTS: Before and immediately after reintubation, serum potassium levels were measured. Two minutes after intubation, premature ventricular contractions, ventricular fibrillation, bradycardia, and finally cardiac arrest were recognized. An increase of serum potassium from 3.19 to 8.64 mmol/L was observed in arterial blood. The patient was immediately resuscitated with chest compressions, intravenous adrenaline, atropine, lidocaine, and sodium bicarbonate. Potassium values normalized within 30 mins. Further treatment in the intensive care unit was uneventful, and the patient was weaned from mechanical ventilation and discharged to a hematology clinic. At present his mental and physical state is satisfactory. CONCLUSIONS: Succinylcholine may cause dangerous arrhythmias in septic and immobilized children. The alternative nondepolarizing agents should be used in such cases. PMID- 17273117 TI - Oral and nasal enteral tube placement errors and complications in a pediatric intensive care unit. AB - OBJECTIVE: To report five cases of errors in the placement of oral/nasal enteral tubes in a pediatric intensive care unit, and to review literature on placement techniques and complication rates. DESIGN: Case series and review of the literature. SETTING: A 19-bed pediatric intensive care unit in a tertiary care pediatric hospital. PATIENTS: A 14-yr-old male with respiratory distress following a near drowning, a 10-yr-old male with recurrent acute lymphocytic leukemia and Pneumocystis carinii pneumonia, a 16-yr-old female with complex congenital heart disease and respiratory failure, a 16-yr-old male with status asthmaticus, and a 2-yr-old male with congenital heart disease. INTERVENTIONS: None. MAIN RESULTS: Five cases of enteral tube placement errors occurred in our combined medical-surgical pediatric critical care unit within the past year. All five resulted in placement of the feeding tube in the respiratory tract, four occurred despite the presence of cuffed endotracheal tubes. Three of the five patients had subsequent worsening of their respiratory status. One developed a pneumothorax, one developed pulmonary hemorrhage, and one developed an increased oxygen requirement. CONCLUSIONS: Patients in the pediatric intensive care unit may have characteristics that place them at an increased risk for misplacement of oral or nasal enteral tubes into the respiratory tract. Placement of enteral tubes into the respiratory tract may cause serious morbidity and possibly mortality. Checking the placement of enteral tubes with traditional methods does not prevent misplacement in the respiratory tree, and new techniques should be considered. PMID- 17273118 TI - Analysis of the evidence for the lower limit of systolic and mean arterial pressure in children. AB - OBJECTIVE: Systolic blood pressure (SBP) and mean arterial pressure (MAP) are essential evaluation elements in ill children, but there is wide variation among different sources defining systolic hypotension in children, and there are no normal reference values for MAP. Our goal was to calculate the 5th percentile SBP and MAP values in children from recently updated data published by the task force working group of the National High Blood Pressure Education Program and compare these values with the lowest limit of acceptable SBP and MAP defined by different sources. DESIGN: Mathematical analysis of clinical database. METHODS: The 50th and 95th percentile SBP values from task force data were used to derive the 5th percentile value for children from 1 to 17 yrs of age stratified by height percentiles. MAP values were calculated using a standard mathematical formula. Calculated SBP values were compared with systolic hypotension definitions from other sources. Linear regression analysis was applied to create simple formulas to estimate 5th percentile SBP and 5th and 50th percentile MAP for different age groups at the 50th height percentile. RESULTS: A 9-21% range in both SBP and MAP values was noted for different height percentiles in the same age groups. The 5th percentile SBP values used to define hypotension by different sources are higher than our calculated values in children but are lower than our calculated values in adolescents. Clinical formulas for calculation of SBP and MAP (mm Hg) in normal children are as follows: SBP (5th percentile at 50th height percentile) = 2 x age in years + 65, MAP (5th percentile at 50th height percentile) = 1.5 x age in years + 40, and MAP (50th percentile at 50th height percentile) = 1.5 x age in years + 55. CONCLUSION: We developed new estimates for values of 5th percentile SBP and created a table of normal MAP values for reference. SBP is significantly affected by height, which has not been considered previously. Although the estimated lower limits of SBP are lower than currently used to define hypotension, these values are derived from normal healthy children and are likely not appropriate for critically ill children. Our data suggest that the current values for hypotension are not evidence-based and may need to be adjusted for patient height and, most important, for clinical condition. Specifically, we suggest that the definition of hypotension derived from normal children should not be used to define the SBP goal; a higher target SBP is likely appropriate in many critically ill and injured children. Further studies are needed to evaluate the appropriate threshold values of SBP for determining hypotension. PMID- 17273119 TI - Do pediatric patients with septic shock benefit from steroid therapy? A critical appraisal of "Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock" by Oppert et al. (Crit Care Med 2005; 33:2457-2464). AB - OBJECTIVE: To review the findings and discuss the implications of studies on the use of low-dose corticosteroids in septic shock. DESIGN: A critical appraisal of "Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock" by Oppert et al. (Crit Care Med 2005; 33:2457 2464) with literature review. FINDINGS: Previous studies have shown that low-dose corticosteroids shorten duration of shock in adults with sepsis, which is confirmed by the results of Oppert et al. The benefit on mortality is much less clear. Review of the literature casts doubt on whether these data can be extrapolated to children. CONCLUSIONS: There is some, albeit limited, evidence for the benefit of low-dose steroids in adults with sepsis. No supporting data are available for the pediatric population; therefore, a randomized controlled trial in septic children is needed. PMID- 17273120 TI - Massive ibuprofen overdose requiring extracorporeal membrane oxygenation for cardiovascular support. AB - OBJECTIVE: Ibuprofen is rarely associated with severe toxicity. We report a massive ibuprofen overdose that resulted in refractory hypotension requiring extracorporeal membrane oxygenation (ECMO) for cardiovascular support. DESIGN: Individual case report. SETTING: Pediatric intensive care unit of a tertiary care hospital. PATIENT: A 14-yr-old male presented with apnea and cardiovascular collapse after a nonaccidental ingestion of approximately 50 g of ibuprofen. His laboratory evaluation demonstrated an anion gap metabolic acidosis and elevated lactate levels. INTERVENTIONS: The patient required pressor support with norepinephrine, phenylephrine, and vasopressin infusions. Due to refractory hypotension, he was placed on ECMO. His serum ibuprofen level at an estimated 5 10 hrs postingestion was 776 microg/mL (therapeutic 20-30 microg/mL). Urine toxicological screen for drugs of abuse, serum acetaminophen, salicylate, and carboxyhemoglobin levels showed that these levels were not elevated. The patient developed high-output renal failure, pulmonary hemorrhage, and gastric bleeding, all of which resolved by hospital day 3. MEASUREMENTS AND MAIN RESULTS: ECMO was discontinued on hospital day 4, inotropic support was discontinued, and the patient was extubated on hospital day 5. He was transferred to an inpatient psychiatric unit on hospital day 9 with no identifiable medical sequelae. CONCLUSIONS: Although ibuprofen overdose typically has few consequences, severe hypotension, renal failure, and gastrointestinal bleeding can occur. We report the first known case of successful ECMO therapy for ibuprofen overdose. PMID- 17273121 TI - Management of abdominal compartment syndrome during extracorporeal life support. AB - OBJECTIVE: To describe the successful use of a peritoneal dialysis catheter for emergent decompression of abdominal compartment syndrome during extracorporeal life support for septic shock. DESIGN: Case report. SETTING: Pediatric intensive care unit at a freestanding tertiary children's hospital. PATIENT: Two-year-old toddler with influenza A complicated by methicillin-resistant Staphylococcus aureus pneumonia and septic shock. INTERVENTIONS: Placement of peritoneal dialysis catheter. MEASUREMENTS AND MAIN RESULTS: Changes in hemodynamic and respiratory parameters. Improvement in extracorporeal membrane oxygenation venous drainage with subsequent survival. CONCLUSIONS: Although the standard therapy for abdominal compartment syndrome is decompressive laparotomy, a minimally invasive percutaneous approach may be effective and should be considered in selected patients. PMID- 17273122 TI - Introduction of Infant Flow nasal continuous airway pressure as the standard of practice in Poland: the initial 2-year experience. AB - OBJECTIVE: The aim of this prospective study was to evaluate whether a change in the standard of newborn care for respiratory insufficiency by widely introducing more aggressive use of nasal continuous airway pressure (nCPAP) and including Infant Flow technology would result in satisfactory outcomes. DESIGN: Prospectively defined analysis. SETTING: Fifty-seven secondary and tertiary care neonatal centers in Poland. PATIENTS: Patients were 1,299 newborns. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We carried out a prospectively defined analysis of 1,299 newborns included in the program between August 1, 2003, and April 30, 2005. The inclusion criterion was the occurrence of symptoms of respiratory failure irrespective of its etiology. Respiratory support was provided with the use of the Infant Flow Advance Driver. The analysis was made on data from prospectively designed questionnaires completed following each infant's treatment. Infants were placed into categories based on clinical indication for use. The primary end point was avoiding tracheal intubation. A high rate of acceptance of the new practice was observed across the substantial demographic and clinical diversity of newborns. Tracheal intubation was avoided in 78% of infants treated electively with nCPAP. Of those being weaned from mechanical ventilation, 61.2% were successfully weaned. Related complications were low (1.4% pneumothorax, 12% nasal injuries). CONCLUSIONS: The new method of nCPAP with Infant Flow was adopted as standard practice in Poland. We monitored its safety and effectiveness over a 2-yr period and found it to be safe and effective as implemented. Additional research is still needed to determine the optimum patient population, strategy for use, and devices. PMID- 17273123 TI - Endotracheal intubation and pediatric status asthmaticus: site of original care affects treatment. AB - OBJECTIVES: Status asthmaticus is a common cause of admission to a pediatric intensive care unit (PICU). Children unresponsive to medical therapies may require endotracheal intubation; however, this treatment carries significant risk, and thresholds for intubation vary. Our hypothesis was that children who sought care at community hospitals received less aggressive treatment and more frequent intubation than children who sought care at a children's hospital. DESIGN: Retrospective cohort study. SETTING: A university-affiliated children's hospital PICU. PATIENTS: We retrospectively examined data from all children older than 2 yrs admitted to the PICU with status asthmaticus between April 1997 and July 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 251 children admitted to the PICU with status asthmaticus, 130 initially presented to the emergency department of a children's hospital and 116 presented to the emergency department of a community hospital. Despite similar illness severity, children presenting to a community hospital were significantly more likely to be intubated than those presenting to a children's hospital (17% vs. 5%; p = .004). In addition, those children intubated at community hospitals were intubated sooner after presentation (2.4 +/- 5.2 vs. 7.5 +/- 5.8 hrs; p = .009), had shorter durations of intubation (71 +/- 73 vs. 151 +/- 81 hrs; p = .02), and had shorter PICU length of stays (129 +/- 82 vs. 230 +/- 84 hrs; p = .01). CONCLUSIONS: Children with status asthmaticus are more likely to be intubated, and intubated sooner, at a community hospital. The shorter duration of intubation suggests that some children may not have been intubated had they presented to a children's hospital or received more aggressive therapy at their community hospital. PMID- 17273124 TI - Validity and reliability of the Behavioural Observational Pain Scale for postoperative pain measurement in children 1-7 years of age. AB - OBJECTIVE: Pain measurement is a necessity in pain treatment but can be difficult in young children. The aim of this study was to evaluate the validity and reliability of the Behavioural Observational Pain Scale (BOPS) as a postoperative pain measurement scale for children aged 1-7 yrs. The scale assesses three elements of pain behaviors: facial expression, verbalization, and body position. DESIGN: A prospective study. SETTING: A day surgery care unit for children and a neurosurgical postoperative care unit. PATIENTS: Seventy-six children aged 1-7 yrs (4.5 +/- 1.8) undergoing elective surgical procedures were observed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study was divided into interrater reliability, concurrent validity, and construct validity. The interrater reliabilities of the observers were very good with a high agreement between the different nurses' BOPS scores. Each item of the BOPS scale ranged from kappa(w) 0.86 to 0.95. In the concurrent validity, BOPS and Children's Hospital of Eastern Ontario Pain Scale scores had a positive correlation indicating that both tools described similar behaviors (r(s) = .871, p < .001). In construct validity, the effect of analgesic was tested before analgesic administration and at 15, 30, and 60 mins after analgesic administration. The differences in BOPS score between the time intervals were significant (p < .01) before administration of analgesia and at 15, 30, and 60 mins. There was also statistical significance in the BOPS score (p < .01) between 15 and 60 mins after administration of analgesia. CONCLUSIONS: With BOPS, the caretaker can evaluate and document pain with high reliability and validity and thereby improve postoperative pain treatment in preschool children. The simple scoring system makes BOPS easy to incorporate in a postoperative unit. PMID- 17273125 TI - Regional and central venous oxygen saturation monitoring following pediatric cardiac surgery: concordance and association with clinical variables. AB - OBJECTIVE: To compare changes in regional cerebral or flank oxygen saturation measured by near-infrared spectroscopy with changes in central venous oxygen saturation (ScvO2) and to determine clinical variables associated with these changes. DESIGN: Prospective observational cohort study. SETTING: University tertiary care center, pediatric cardiac intensive care unit. PATIENTS: Seventy postoperative congenital cardiac surgical patients (median age 0.3 yrs; interquartile range 0.02-0.46 yrs). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured temporally correlated regional oxygen saturation (rSO2) with hematologic (hematocrit), biochemical (arterial blood gas, ScvO2, and lactate) and physiologic (temperature, heart rate, mean blood pressure, and pulse oximetry) variables in the first postoperative day. Cerebral and flank rSO2 were strongly correlated with ScvO2, in both cyanotic or acyanotic patients and single or two-ventricle physiology with and without aortic arch obstruction (all p < .001). However, individual values had wide limits of agreement on Bland-Altman analysis. The correlations of change in these measurements were weaker but still significant (all p < .0001), again with wide limits of agreement. Similar direction of change in cerebral rSO2 and ScvO2 was present 64% (95% confidence interval, 55-73%) of the time. Change in arterial pressure of carbon dioxide (delta PaCO2) was associated with cerebral delta rSO2 (delta PaCO2 beta = 0.35, p < .0001) but not flank delta rSO2 or delta ScvO2. A pattern of relative cerebral desaturation (flank rSO2 > cerebral rSO2) was noted in a majority of patients (81%) with two-site monitoring regardless of bypass method or age. CONCLUSIONS: Neither individual values nor changes in rSO2 are interchangeable measures of ScvO2 in postoperative pediatric cardiac patients. The unique relationship between changes in PaCO2 and cerebral rSO2 supports the hypothesis that cerebral near-infrared spectroscopy monitors regional cerebral oxygenation. Clinical application of this monitor must include recognition of the clinical variables that affect regional brain oxygenation. PMID- 17273126 TI - [Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome: middle age?]. PMID- 17273127 TI - Characterization of overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis according to antimitochondrial antibodies status. AB - AIMS: Codification of variant forms between Primary Biliary Cirrhosis (PBC) and Autoimmune Hepatitis (AIH) has not been definitively standardized. The aim of this study was to compare among 102 consecutive patients, 2 subsets of overlap syndrome (OS, N=21) with and without antimitochondrial antibody (AMA) to two groups of patients with typical PBC (N=43) or AIH (N=38). METHODS: OS was defined by the presence in the same patient of at least 2 of 3 accepted criteria of PBC and AIH. Twelve patients with OS were AMA negative and 9 were AMA positive. RESULTS: A lower level of alanine transaminase (139+/-48 vs 269+/-154 IU/L, P<0.05) and a trend towards a higher level of alkaline phosphatase or gamma glutamyl transpeptidase was observed in OS without AMA than in OS with AMA (693+/ 200 vs 544+/-124 IU/L; 370+/-66 vs 241+/-77 IU/L, respectively). All AMA-negative patients with OS had antinuclear and/or anti-smooth muscle antibodies. OS without AMA differed from those with AMA in that they had more severe bile duct damage including destructive cholangitis (P<0.05), ductopenia (P<0.05), ductular hyperplasia (P<0.05) and a higher METAVIR fibrosis score (2.5+/-0.3 vs 1.3+/-0.3, P<0.05). The response to therapy was not different between PBC, AIH and OS. CONCLUSIONS: According to the presence of AMA, 2 homogeneous subgroups of patients with overlap syndrome between PBC and AIH may be identified. AMA status affects clinical presentation and liver disease severity of OS. PMID- 17273128 TI - Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis: a retrospective study of 115 cases of autoimmune liver disease. AB - OBJECTIVE: The aim of this retrospective study was to compare clinical, biological, and histological features and treatment response in 115 patients with overlap syndrome (OS), autoimmune hepatitis (AIH) or primary biliary cirrhosis (PBC). METHODS: Consecutive patients with AIH, PBC or OS followed between 1984 and 2005 in five different centers were included. All data were re-evaluated using current diagnostic criteria of each disease. RESULTS: Fifteen patients had OS (13 females), 48 AIH (40 females) and 52 PBC (49 females). Patients with OS were significantly younger than patients with PBC (median age: 44 vs 59 years). Jaundice (20%) and pruritus (20%) were the main initial symptoms in OS. Patients with OS had serum transaminase and gammaglobulin levels significantly higher than patients with PBC; serum alkaline phosphatase, gamma-glutamyl-transpeptidase and IgM levels were significantly higher in OS than in patients with AIH. Histological analysis showed moderate or severe piecemeal necrosis in 86% and destructive cholangitis in 93% in OS group. Among 11 patients with OS treated with ursodeoxycholic acid (UDCA) or immunosuppressors alone, only 6 had a complete biochemical response. In contrast, all patients with OS receiving combined therapy, as first or second line, responded, 5 patients to the combination corticosteroids-azathioprine-UDCA and 2 to the combination cyclosporine-UDCA. CONCLUSION: OS is not rare and accounts for 13.9% of patients with autoimmune liver disease in our series. Combination of immunosuppressors and UDCA appears the most efficient treatment in these patients. PMID- 17273129 TI - [Infection and variceal bleeding in cirrhosis]. AB - Endotoxemia and bacterial infection are frequent in patients with cirrhosis. They alter systemic and splanchnic hemodynamics, worsen coagulation disorders, impair liver function and thus may induce variceal bleeding. In variceal bleeding, bacterial infection favours failure to control bleeding, early rebleeding, and death. In patients with cirrhosis and variceal bleeding, antibiotic-prophylaxis decreases bacterial infection and the incidence of early rebleeding, and, more important, significantly decreases the death rate in these patients. PMID- 17273130 TI - [Emerging concepts in colorectal serrated polyps]. AB - Colorectal serrated polyps are heterogeneous epithelial lesions characterized by a serrated architecture. They include the classical hyperplastic polyps and the much rarer serrated adenomas and mixed polyps. Whereas serrated adenomas are composed of an unequivocal adenomatous epithelium with architectural serrated, mixed polyps include two separate hyperplastic and adenomatous components. During the past few years, another type of serrated polyp with only very subtle proliferation abnormalities has been described. These atypical serrated polyps may occur either sporadically or in the context of colorectal polyposis. Despite their close resemblance to traditional hyperplastic polyps, some authors argued that they should be regarded as authentically neoplastic lesions and have proposed to call them "sessile serrated adenomas". Their malignant potential requires their removal when discovered during colonoscopy. This article reviews the histological features, the endoscopic appearance, the natural history and the molecular phenotype of the different categories of serrated polyps and introduces the concept of "serrated neoplastic pathway" in the development of colorectal cancer. PMID- 17273131 TI - [Surgical treatment of recurrent locoregional rectal cancer]. AB - Local recurrence (LR) after curative surgery for rectal cancer occurs in 4 to 33% of cases especially if surgery is sub-optimal (without total excision of the mesorectum). In many cases, diagnosis of LR is made at a late stage because of the high rate of asymptomatic patients, 56% in the experience of the Mayo Clinic. MRI and PETscan are most effective for assessing local and general extension, with a high diagnostic accuracy. Surgical treatment alone or with radiation (preoperative and/or intraoperative) is the only curative treatment of LR with R0 resectability rates of 30% to 45%. Morbidity and mortality rates are high, especially for total exenteration and abdomino-sacral resection. After curative surgery, 5-year global survival is between 30% and 40%. Palliative resection of macroscopic residues is not recommended. Careful patient selection for curative surgery is the best way to optimize treatment in these cases. PMID- 17273132 TI - [Linitis of the colon with peritoneal carcinosis treated with cytoreductive surgery and intraperitoneal hyperthermic chemotherapy]. PMID- 17273133 TI - [Large size colonic adenoma without carcinoma revealed by a portal vein thrombosis (L)]. PMID- 17273134 TI - Management of gastro-esophageal reflux disease in primary care. Results from an observational study of 2,474 patients (AO). AB - OBJECTIVE: The aim of the present study was to describe the management of gastro esophageal reflux disease (GERD) by primary care physicians (PCPs). METHODS: This prospective survey was conducted in patients with suspected or previously diagnosed GERD. PCPs completed questionnaires at first consultation (M0) and at a 3-month follow-up visit (M3). RESULTS: 2 474 patients were available for analysis at M0 and 1 993 at M3. GERD was the reason for consultation in 84% of patients; 33% were consulting about reflux symptoms for the first time. Symptoms occurred once daily in 55% of patients and were considered very disruptive or incapacitating by 51%. Upper gastrointestinal endoscopy was performed at any time in 57% of patients and at M0 in 20%. Only 48% of demands for endoscopy agreed with current recommendations and this rate was not influenced by PCP training in the previous 6 months. Lifestyle measures were recommended in 95% of patients at M0. Proton pump inhibitors were prescribed in 98%, to be taken "on-demand" in 22 57% depending on symptom frequency. Therapeutic management was considered as very satisfactory by 81% of patients. CONCLUSIONS: GERD managed in primary care is severe, leading to expensive, but effective diagnostic investigations and treatments. Agreement with recommendations for endoscopy is poor. PMID- 17273135 TI - Proton pump inhibitors in general medicine. Comparison of routine practices with marketing authorization indications. AB - OBJECTIVE: To determine whether inaugural prescriptions for proton pump inhibitors (PPI) written by general practitioners in the Grenoble region are in non-compliance with the indications of the French drug marketing authorization. METHODS: The study was conducted on all inaugural PPI prescriptions written by general practitioners in Grenoble region between March 1 and March 31, 2004. Analyses were performed on a random sample of 600 representative prescriptions. A questionnaire was sent to the general practitioners who had written these prescriptions. There were 255 responses which could be analyzed. RESULT: Among the 19,983 prescriptions for PPIs written in March 2004, 4, 442 (22.8%) were first-time treatments. 85.9% of them were issued by general practitioners. The main reasons for prescription identified in the study sample were the association with other drugs [56.1%; 95%CI 50.0-62.2], gastroesophageal reflux disease [29.4%; 95%CI 23.8-35.0] and dyspepsia [11.4%; 95%CI 7.5-15.3]. The rate of non compliance with the marketing authorization was 46.3% [95%CI 40.2-52.4], including 20.4% [95%CI 15.5-25.3] for inappropriate medical indications. CONCLUSION: General practitioners were the principal prescribers of inaugural PPI treatments. Even after excluding prescriptions which were non-compliant because of a regulatory problem, one out of five prescriptions were written for inappropriate medical indications. PMID- 17273136 TI - [Ulcerative colitis and anti-TNFalpha]. PMID- 17273137 TI - [Ulcerative colitis associated with rectocolitis hemorrhagic: successful treatment with infliximab]. PMID- 17273138 TI - [An unusual perianal abscess]. AB - Aggressive angiomyxoma (AA) is a mesenchymal tumour occurring in connective tissue of the perineum or lower pelvis with a marked tendency to local recurrence but which usually does not metastasize. Only 130 cases had been reported to date. We report the case of a 58-year-old woman, presenting with a pelvi-perineal mass, which was considered to be an anal abscess. After surgical excision, an AA was diagnosed, with classical histological features (myxoid and vascular components) and which was positive for vimentin and CD34. This case report shows that clinical diagnosis of AA is difficult and that delayed diagnosis can prevent optimal treatment of these tumors. PMID- 17273139 TI - [Anal abscess with a tuberculous origin: report of two cases and review of the literature]. AB - Gastrointestinal tuberculosis represents 1% of extrapulmonary tuberculoses and only sporadic cases of anal tuberculosis have been reported in the literature. We report two cases of tuberculous anal abscess and a review of the literature for diagnosis and treatment. PMID- 17273140 TI - [Autoimmune thrombopenia associated with hepatitis B reactivation (reverse seroconversion) after autologous hematopoietic stem cell transplantation]. AB - We report a case of autoimmune thrombocytopenia associated with acute reverse seroconversion of hepatitis B in a patient who was initially hepatitis B virus surface antigen negative and hepatitis B virus surface antibody positive. Reactivation occurred 9 months after chemotherapy with anti-CD 20 monoclonal antibodies and autologous hematopoietic stem cell transplantation for lymphoma had been performed. After non specific polyglobulin injections and treatment with adefovir dipivoxil, thrombocytopenia and viral replication were controlled. Seroconversion for both HBe and HBs occurred at 5 months. Adefovir was stopped 4 months later with no relapse during fifteen months of follow-up. This case shows that patients who have had previous contact with hepatitis B virus should be monitored if they become immunosuppressed, even if anti-HBs were initially present. PMID- 17273141 TI - [Chylous ascites revealing a systemic lupus erythematosus (L)]. PMID- 17273142 TI - [Metastatic transitional cell carcinoma with high CA 19.9 serum levels]. AB - We report the case of a 75-year-old woman with liver metastases of a urothelial carcinoma accompanied by a marked increased in CA 19-9 serum level. The mechanisms leading to this elevation, similar to that observed in biliary tract diseases, are discussed. PMID- 17273143 TI - Acute recurrent biliary pancreatitis associated with the ABCB4 gene mutation. AB - The ABCB4 gene codes for a protein involved in the transport of phosphatidylcholine across the canalicular membrane of the hepatocyte. ABCB4 gene defects have been associated with progressive familial intrahepatic cholestasis type 3, intrahepatic cholestasis of pregnancy, adult biliary cirrhosis and the more recently described low phospholipid associated cholelithiasis syndrome. The present paper describes 2 probands with a long history of recurrent pancreatitis and cholelithiasis and the same heterozygous, as yet undescribed del 3683>3688 within exon 28 of the ABCB4 gene resulting in a loss of function. This report shows that ABCB4 mutations may cause acute recurrent biliary pancreatitis. PMID- 17273146 TI - Volatilization and recovery of mercury from mercury-polluted soils and wastewaters using mercury-resistant Acidithiobacillus ferrooxidans strains SUG 2 2 and MON-1. AB - Iron-oxidizing bacterium, Acidithiobacillus ferrooxidans, is one of the most important bacteria for the bioleaching of copper and gold ores. In order to use the mercury reducing activity of A. ferrooxidans for the bioremediation of mercury, mercury-resistant A. ferrooxidans strains SUG 2-2 and MON-1 were screened among 150 strains of iron-oxidizing bacteria isolated from natural environments. It was found that strains SUG 2-2 and MON-1 have a novel ferrous iron-dependent mercury volatilization activity as well as an NADPH-dependent mercury reductase activity. Strain MON-1 has an organomercurial lyase-like activity and grew most rapidly in an iron medium with 0.1 microM p chloromercuribenzoic acid among 11 A. ferrooxidans strains tested. Nearly 100% of the total mercury in mercury-polluted soil or mercury wastewater was volatilized and recovered by incubating SUG 2-2 or MON-1 cells in 20 ml of an acidified water (pH 2.5) with ferrous iron, suggesting that these mercury-resistant strains can be used for the bioremediation of inorganic and organic mercurial compounds. We show for the first time that MON-1 cells immobilized in polyvinyl alcohol (PVA) resins could efficiently volatilize mercury from 2 L of a synthetic mercury polluted wastewater (pH 2.5) containing 40 microM Hg(2+) and ferrous iron. The MON-1-immobilized PVA resins were used repeatedly. PMID- 17273147 TI - Membrane-coupled fungi reactor--an innovative approach to bioremediation of hazardous dye wastewater. AB - Owing to the inherent shortcomings of conventional biological dye effluent treatment processes, researchers have proposed diverse intriguing approaches that await practical implementation. This study demonstrates the feasibility of an innovative membrane-coupled fungi reactor. Preliminary batch tests revealed the noteworthy role of biosorption along with biodegradation in decoloration, and also confirmed excellent decoloration even in the presence of hardly biodegradable polyvinyl alcohol besides recalcitrant dye in the wastewater. Conversely, the continuous reactor achieved stable 97% total organic carbon (TOC) and 99% color removal with a hydraulic retention time (HRT) of 15 h. A marked decrease in the UV absorbance of the membrane permeate, and the detection of short-chain aliphatic acids in the permeate provided evidence of the subsequent biodegradation of the aromatic group following the breakdown of the color imparting chromophoric group of the dye. PMID- 17273148 TI - Identification of subjects for social responsibility education at universities and the present activity at the university of Tokyo. AB - The management of corporate social responsibility (CSR) has recently become a critical concern for companies in advanced countries. For universities, there is a requirement to contribute to the promotion of CSR, resulting in graduates who have sufficient cognition of and a good attitude towards CSR. In addition, universities have social responsibilities, which can be called "University Social Responsibility (USR)." On the basis of the concepts of the guidelines for CSR in the "Green Paper," which was presented by the European Committee (EC) in 2001, we provide a perspective here on what factors dictate the establishment of education programs for social responsibilities at universities. These factors include an outline of the concepts and the significance of CSR, social ethics and the morals of higher education and research, compliances, human resource management, human rights, safety and health in academic settings, and various concerns regarding environmental safety and preservation. Additionally, through the concept postulated here for social responsible education, in this paper, we introduce the present activity at the University of Tokyo (UT) in terms of the education program for CSR and USR, proposing that the future establishment of university wide education programs based on the concept of CSR and the value of sustainability is required at UT. PMID- 17273150 TI - Direct analysis of diesel exhaust particles by fragmentation-free mass spectrometry using ion attachment mass spectrometry. AB - We analyzed diesel exhaust particles immediately by fragmentation-free mass spectrometry using ion attachment mass spectrometry (IA-MS). IA-MS can be used to measure labile organic compounds without any fragmentation. Ionization without fragmentation can be performed because a neutral molecule becomes an adduct ion by the attachment of Li(+) with a small amount of energy by the Coulomb force. A third-body gas, such as 100 Pa N(2), removes any excess energy of the adduct ion and makes it stable. The aim is to be able to measure the preprocessing of the sample promptly using this analysis. In a direct analysis of diesel exhaust particles using IA-MS, many compounds (including some unknown chemicals) were detected. In the mass spectrum consisting of the ion peaks of many compounds, it is possible that the source and load factor to the environment are considered as one index. PMID- 17273149 TI - Approach to and effectiveness of environmental risk education of public: case of indoor environmental risk consciousness in beijing. AB - Increasing concern regarding environmental risk in China has led to a need for education on environmental health and safety. In this paper, we report on four main ways to enhance environmental risk consciousness of the public. By investigating residents' indoor environmental risk consciousness in Beijing, we appraised the effectiveness of current environmental risk education approaches. Our investigation showed that the indoor environmental risk consciousness of most residents is high. Most residents have some environmental risk knowledge, have a strong desire to demand better quality of their living environment, and would like to invest in it. However, people's actual behavior in terms of reducing health risk factors fall comparatively behind. It is important to use all approaches to carry out environmental risk education. Not only should new knowledge be imparted, but the public should also be trained how to take precautions against pollution. The extension of education from campus to society is also necessary. PMID- 17273151 TI - Specific dual beam fluorometry analysis of benzo[a]pyrene and benzo[k]fluoranthene in diesel exhaust particulate samples. AB - We developed a specific analysis method for benzo[a]pyrene (B[a]P) and benzo[k]fluoranthene (B[k]F) using dual beam fluorometry. B[a]P and B[k]F exhibited two specific fluorescence intensities (up to 10-fold) compared with 22 other polycyclic aromatic hydrocarbons (PAHs) at 370 nm excitation and 429 nm emission wavelengths, and similarly at 395 nm excitation and 429 nm emission wavelengths. The concentrations of these compounds in diesel exhaust particles were calculated from two calibration curves determined using a mixture of 24 PAH standards. The precision of this detection method was compared with that of conventional high-performance liquid chromatography/fluorescene detector (HPLC/FLD), and our method gave accurate values within the analytical standard deviations. The monitoring method developed in this study will enable more rapid and easier detection. PMID- 17273152 TI - Influence of particle size preparation of MSW incineration residues on heavy metal leaching behavior in leaching tests. AB - This study examines the influence of particle size preparation on leaching tests of heavy metal leaching behavior of municipal solid waste (MSW) incineration fly ash and MSW melting slag. The MSW incineration fly ash and melting slag were divided into 2-3 fractions by sieving. The metal contents of the respective fractions were determined and the representativeness of the samples was verified. Differences in the metal contents of the fractions with different particle sizes were significant for MSW incineration fly ash. Therefore, particle size preparation by sieving should not be done prior to these leaching tests. In contrast, differences in metal contents of different particle sizes of melting slag were not significant. Therefore, sample fractions with identical metal contents are obtainable by sieving. The metal leaching quantities by the Japanese Leaching Test Method No. 19 (JLT-19) depend on the chemical stability and particle size preparation of slag. The modified basicity, [(CaO+MgO+Na(2)O+K(2)O) / (SiO(2)+Al(2)O(3))], is useful as an index of the chemical stability of slag. PMID- 17273153 TI - Increased blood pressure reactivity to dietary salt in patients with the metabolic syndrome. AB - The metabolic syndrome is a predictor of type II diabetes mellitus and cardiovascular disease. The mechanisms of the increased blood pressure (BP) in patients with the metabolic syndrome are poorly understood. We investigated if salt-sensitivity is a characteristic of the metabolic syndrome. A total of 301 subjects (87 male subjects, 214 female subjects) of 41.5+/-0.7 years of age completed a salt sensitivity test, and were evaluated for the presence of metabolic syndrome. BP and 24-h sodium excretion were obtained under usual, high- and low-salt intakes. BP reactivity to salt was markedly increased in subjects with the metabolic syndrome; its magnitude was directly related to the severity of the syndrome. Reducing dietary salt from the average usual intake (8.2 g/day) to nearly 2.3 g/day lowered systolic blood pressure (SBP) by 8.7+/-1.3 mm Hg in subjects with four and five traits, 6.0+/-1.1 in those with three traits and failed to modify the BP of subjects with one or no traits of the syndrome (P < 0.0001). Salt restriction reduced the percentage of subjects with metabolic syndrome that were hypertensive (8.2 g/day of salt) from 23.8 to 8.2% (chi2: 23.6; P<0.0001). BP of non-hypertensive subjects with metabolic syndrome was also significantly reduced by salt restriction (7.1+/-1.5 and 4.2+/-1.1 mm Hg in those with four or five traits and three traits, respectively). In conclusion, the metabolic syndrome is a strong clinical predictor of salt sensitivity. The enhanced BP reactivity to dietary salt observed in subjects with the metabolic syndrome, may determine the increased BP levels commonly associated with the syndrome. PMID- 17273155 TI - Hypertension and fatty liver: guilty by association? AB - Essential hypertension is associated with the metabolic syndrome, insulin resistance and the development of fatty liver. Fatty liver disease is a spectrum of liver diseases ranging from simple hepatic steatosis through steato-hepatitis to cirrhosis and hepatoma. The purpose of this review is to discuss the evidence for an association between essential hypertension and non-alcoholic fatty liver disease, and to consider the diagnosis and management of non-alcoholic fatty liver disease. We conclude that it is important to consider the diagnosis of fatty liver disease in hypertensive patients, to measure the liver function tests at diagnosis and not to ignore minor elevations of serum aminotransferases. Hypertensive patients with raised liver enzymes should be referred for further assessment, particularly if risk factors for progressive liver disease, such as obesity and diabetes, are present. PMID- 17273154 TI - Association between body composition and blood pressure in a contemporary cohort of 9-year-old children. AB - Elevated blood pressure (BP) in children is an early risk factor for cardiovascular disease and is positively associated with body mass index (BMI). However, BMI does not distinguish between fat and lean masses, and the relationship of BP in children to different elements of body composition is not well established. BP, BMI and body composition were measured in 6863 children enrolled in the Avon Longitudinal Study of Parents and Children. Fat mass, lean mass and trunk fat were assessed using dual-energy X-ray absorptiometry. After full adjustment for confounders, total body fat and BMI were positively associated with systolic blood pressure (SBP) (beta=3.29, 95% confidence interval CI 3.02, 3.57 mm Hg/standard deviation (s.d.) and beta=3.97, 95% CI 3.73, 4.21 mm Hg/s.d., respectively) and diastolic blood pressure (DBP) (beta=1.26, 95% CI 1.05, 1.46 mm Hg/s.d. and beta=1.37, 95% CI 1.19, 1.54 mm Hg/s.d., respectively). SBP was also positively associated with lean mass (beta=3.38, 95% CI 2.95, 3.81 mm Hg/s.d.), and weakly associated with trunk fat (beta=1.42, 95% CI -0.06, 2.90 mm Hg/s.d., independent of total fat mass), which was robust in girls only. The association between lean mass and SBP remained even after accounting for fat mass. SBP in 9-year-old children is independently associated with fat mass and lean mass and, to a lesser extent, trunk fat in girls. In this analysis, because both fat and lean masses are associated with BP, BMI predicts BP at least as well as these components of body composition. PMID- 17273156 TI - Hypertension in an urban population--who is treated with what and how well? PMID- 17273157 TI - Altered renal folate handling in hypertensive patients with nephroangiosclerotic damage. PMID- 17273158 TI - Age- and gender-dependent association of the -344C/T polymorphism of CYP11B2 with blood pressure in European populations. PMID- 17273159 TI - Aberrant mineralization of connective tissues in a mouse model of pseudoxanthoma elasticum: systemic and local regulatory factors. AB - Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene, but the cellular and molecular events leading to aberrant mineralization of soft tissues are unknown. To characterize the mineralization process, we examined a PXE animal model, the Abcc6-/- mouse, with respect to specific proteins serving as inhibitors of mineralization. The levels of calcium and phosphate in serum of these mice were normal, but the Abcc6-/- serum had less ability to prevent the mineral deposition induced by inorganic phosphate in a cell culture system. Addition of fetuin-A to the culture system prevented the mineralization. The calcium x phosphate product was markedly elevated in the mineralized vibrissae of Abcc6-/- mice, an early biomarker of the mineralization process, consistent with histopathologic findings. Levels of fetuin-A were slightly decreased in Abcc6-/- serum, and positive immunostaining for matrix-gla-protein (MGP), fetuin-A, and ankylosis protein (Ank) as well as alkaline phosphatase activity were strongly associated with the mineralization process. In situ hybridization demonstrated that the genes for MGP and Ank were expressed locally in vibrissae, whereas fetuin-A was expressed highly in the liver. These data suggest that the deposition of the bone-associated proteins spatially coincides with mineralization and actively regulates this process locally and systemically. PMID- 17273160 TI - Skin contact irritation conditions the development and severity of allergic contact dermatitis. AB - Irritant contact dermatitis (ICD) is a frequent inflammatory skin disease induced by skin contact with low molecular weight chemicals such as haptens endowed with proinflammatory properties. Allergic contact dermatitis (ACD) is a frequent complication of ICD and is mediated by hapten-specific T cells primed in lymph nodes by skin emigrating dendritic cells. The aim of this study was to analyze the relationship between ICD and ACD to 2,4-dinitrofluorobenezene (DNFB) in C57BL/6 and BALB/C mice, which develop a severe and a moderate skin inflammation, respectively. Upon a single skin painting with DNFB, C57BL/6 developed within hours a more severe dose-dependent ICD response as compared to BALB/C mice, which was associated with enhanced upregulation of IL-1beta, IL-6, and IL-10. Skin exposure to a low dose of DNFB resulted, in both strains, in a low ICD that resolved in a few hours. Alternatively, skin painting with either an intermediate or a high DNFB concentration induced an ICD that subsequently gave rise to an ACD reaction whose intensity was proportional to the magnitude of the ICD response and was more severe in C57BL/6 mice than in BALB/C mice. In conclusion, the hapten-induced skin contact irritation conditions the development and the severity of ACD. PMID- 17273161 TI - BRAF mutations in multiple sebaceous hyperplasias of patients belonging to MYH associated polyposis pedigrees. AB - The characteristics of sebaceous gland hyperplasia (SGH) consist of yellowish or skin-colored papules and nodules. Chronic sun exposure and immunosuppressed conditions are the main environmental risk factors, whereas chronological aging regulated by hormones and molecular changes are the intrinsic risk factors. We have evaluated the contribution of BRAF, K-Ras, and N-Ras mutations to the pathogenesis of SGHs in four patients belonging to three MYH-associated polyposis (MAP) pedigrees. MAP is an autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. Immunohistochemistry of mismatch repair and APC proteins was performed. DNA isolated from blood lymphocytes and formalin-fixed or paraffin-embedded SGHs was PCR amplified and sequenced. In the SGH patients, we detected T1796A heterozygous substitution (V600E) in the BRAF gene. Compound biallelic germline MYH mutations (Y165C/G382D, R168H/379delC, and Y90X/delGGA464) were detected in the MAP patients. In contrast to the majority of melanocytic lesions, activating hotspot mutations in BRAF have not been involved so far in the pathogenesis of SGH. BRAF mutation is not a specific marker of melanocytic cancerogenesis, and it can also be involved in SGHs. In both melanocytic and non melanocytic skin tumors, BRAF mutation is linked to early tumorigenesis events. PMID- 17273163 TI - In situ identification of genes regulated specifically in fibroblasts of human basal cell carcinoma. AB - Basal cell carcinoma (BCC) is characterized by slow growth, virtual absence of metastases, and strong stroma-dependency. Cancer-associated fibroblasts (CAFs) in the tumor stroma influence tumor growth, invasion, and metastasis. To comprehensively characterize CAFs of BCC in their in situ cancer environment, laser capture microdissection, linear gene amplification, microarray analysis, and quantitative real-time PCR (qRT-PCR) were combined. Pair-wise comparison of gene expression of microdissected CAFs and corresponding normal perifollicular fibroblasts identified 65 genes that were significantly upregulated in at least two of three different patients. Among the annotated genes, as many as 13 genes encoded secreted proteins, of which six were previously implicated as CAF associated proteins in various tumor types. Four of the seven novel CAF genes- matrix Gla-protein, secreted frizzled-related protein 2, angiopoietin-related protein-2, and platelet-derived growth factor receptor-like protein--were selected for further analyses by qRT-PCR and were found to be frequently upregulated in CAFs of three independent BCC tissues. Analyses of CAFs from squamous cell cancer, prostate cancer, and colon cancer did not indicate that these genes were upregulated in these cancers. This study thus validates a novel approach for comprehensive characterization CAFs in their in situ environment of BCC. The results suggest a specific expression profile of CAFs in BCC possibly accounting for disease-specific pathological roles. PMID- 17273162 TI - Targeting effector memory T cells with the small molecule Kv1.3 blocker PAP-1 suppresses allergic contact dermatitis. AB - The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows for selective pharmacological suppression of effector memory T (T(EM)) cells without affecting the function of naive and central memory T cells. We here investigated whether PAP-1, a small molecule Kv1.3 blocker (EC50=2 nM), could suppress allergic contact dermatitis (ACD). In a rat model of ACD, we first confirmed that the infiltrating cells in the elicitation phase are indeed CD8+ CD45RC- memory T cells with high Kv1.3 expression. In accordance with its selective effect on T(EM) cells, PAP-1 did not impair sensitization, but potently suppressed oxazolone-induced inflammation by inhibiting the infiltration of CD8+ T cells and reducing the production of the inflammatory cytokines IFN-gamma, IL-2, and IL-17 when administered intraperitoneally or orally during the elicitation phase. PAP-1 was equally effective when applied topically, demonstrating that it effectively penetrates skin. We further show that PAP-1 is not a sensitizer or an irritant and exhibits no toxicity in a 28-day toxicity study. Based on these results we propose that PAP-1 could potentially be developed into a drug for the topical treatment of inflammatory skin diseases such as psoriasis. PMID- 17273164 TI - Possible involvement of exon 31 alternative splicing in phenotype and severity of epidermolysis bullosa caused by mutations in PLEC1. PMID- 17273165 TI - Mutation in Mpzl3, a novel [corrected] gene encoding a predicted [corrected] adhesion protein, in the rough coat (rc) mice with severe skin and hair abnormalities. AB - The rough coat (rc), an autosomal-recessive mutation, arose spontaneously in C57BL/6J mice. Homozygous rc mice develop severe skin and hair abnormalities, including cyclic and progressive hair loss and sebaceous gland hypertrophy. The rc locus was previously mapped to Chromosome 9. To elucidate the genetic basis underlying the rc phenotype development, we carried out positional cloning, and mapped the rc locus to a 246-kb interval. We identified a missense mutation within a novel open reading frame in the rc/rc mice, which is predicted to encode a cell adhesion molecule with the highest homology to myelin protein zero (MPZ) and myelin protein zero-like 2 (MPZL2, also called epithelial V-like antigen). We therefore named this gene Mpzl3 (myelin protein zero-like 3). The mutation in the rc/rc mice occurred at a highly conserved residue within the conserved Ig-like V type domain, thus likely altering the MPZL3 protein function. Reverse transcriptase-PCR and Western blot analyses revealed expression of the Mpzl3 gene in various adult organs, including the skin. Using indirect immunofluorescence, we detected MPZL3 protein in the keratinocytes and sebocytes in the skin. Results from this study identified a novel gene encoding a predicted adhesion protein whose mutation in the rc/rc mice likely caused the rc phenotype. PMID- 17273166 TI - Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata). AB - Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its expression and effects on immune cells in a C3H/HeJ mouse model for AA. During early stages of AA development, the number of SP-immunoreactive nerve fibers in skin is increased, compared to non-affected mice. However, during advanced stages of AA, the number of SP-immunoreactive nerves and SP protein levels in skin are decreased, whereas the expression of the SP-degrading enzyme neutral endopeptidase (NEP) is increased, compared to control skin. In AA, NK-1R is expressed on CD8+ lymphocytes and macrophages accumulating around affected hair follicles. Additional SP supply to the skin of AA-affected mice leads to a significant increase of mast cell degranulation and to accelerated hair follicle regression (catagen), accompanied by an increase of CD8+ cells-expressing granzyme B. These data suggest that SP, NEP, and NK-1R serve as important regulators in the molecular signaling network modulating inflammatory response in autoimmune hair loss. PMID- 17273169 TI - Disruption of methylarginine metabolism impairs vascular homeostasis. AB - Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA) are endogenously produced amino acids that inhibit all three isoforms of nitric oxide synthase (NOS). ADMA accumulates in various disease states, including renal failure, diabetes and pulmonary hypertension, and its concentration in plasma is strongly predictive of premature cardiovascular disease and death. Both L-NMMA and ADMA are eliminated largely through active metabolism by dimethylarginine dimethylaminohydrolase (DDAH) and thus DDAH dysfunction may be a crucial unifying feature of increased cardiovascular risk. However, despite considerable interest in this pathway and in the role of ADMA as a cardiovascular risk factor, there is little evidence to support a causal role of ADMA in pathophysiology. Here we reveal the structure of human DDAH-1 and probe the function of DDAH-1 both by deleting the DDAH1 gene in mice and by using DDAH-specific inhibitors which, as we demonstrate by crystallography, bind to the active site of human DDAH-1. We show that loss of DDAH-1 activity leads to accumulation of ADMA and reduction in NO signaling. This in turn causes vascular pathophysiology, including endothelial dysfunction, increased systemic vascular resistance and elevated systemic and pulmonary blood pressure. Our results also suggest that DDAH inhibition could be harnessed therapeutically to reduce the vascular collapse associated with sepsis. PMID- 17273168 TI - Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. AB - Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown. Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO(*)). Here we show that aldosterone (10(-9)-;10(-7) mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO(*) levels-similar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMP response element modulator (CREM) to inhibit cyclic AMP-response element binding protein (CREB)-mediated G6PD transcription. In vivo, infusion of aldosterone decreased vascular G6PD expression and impaired vascular reactivity. These effects were abrogated by spironolactone or vascular gene transfer of G6pd. These findings demonstrate that aldosterone induces a G6PD-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6PD activity. PMID- 17273170 TI - Brain glucose metabolism controls the hepatic secretion of triglyceride-rich lipoproteins. AB - Increased production of very low-density lipoprotein (VLDL) is a critical feature of the metabolic syndrome. Here we report that a selective increase in brain glucose lowered circulating triglycerides (TG) through the inhibition of TG-VLDL secretion by the liver. We found that the effect of glucose required its conversion to lactate, leading to activation of ATP-sensitive potassium channels and to decreased hepatic activity of stearoyl-CoA desaturase-1 (SCD1). SCD1 catalyzed the synthesis of oleyl-CoA from stearoyl-CoA. Curtailing the liver activity of SCD1 was sufficient to lower the hepatic levels of oleyl-CoA and to recapitulate the effects of central glucose administration on VLDL secretion. Notably, portal infusion of oleic acid restored hepatic oleyl-CoA to control levels and negated the effects of both central glucose and SCD1 deficiency on TG VLDL secretion. These central effects of glucose (but not those of lactate) were rapidly lost in diet-induced obesity. These findings indicate that a defect in brain glucose sensing could play a critical role in the etiology of the metabolic syndrome. PMID- 17273171 TI - Regulatory T cell development in the absence of functional Foxp3. AB - Although the development of regulatory T cells (T(reg) cells) in the thymus is defined by expression of the lineage marker Foxp3, the precise function of Foxp3 in T(reg) cell lineage commitment is unknown. Here we examined T(reg) cell development and function in mice with a Foxp3 allele that directs expression of a nonfunctional fusion protein of Foxp3 and enhanced green fluorescent protein (Foxp3DeltaEGFP). Thymocyte development in Foxp3DeltaEGFP male mice and Foxp3DeltaEGFP/+ female mice recapitulated that of wild-type mice. Although mature EGFP(+) CD4(+) T cells from Foxp3DeltaEGFP mice lacked suppressor function, they maintained the characteristic T(reg) cell 'genetic signature' and failed to develop from EGFP(-) CD4(+) T cells when transferred into lymphopenic hosts, indicative of their common ontogeny with T(reg) cells. Our results indicate that T(reg) cell effector function but not lineage commitment requires the expression of functional Foxp3 protein. PMID- 17273172 TI - Cell cycle and cell death associates in western France. PMID- 17273173 TI - The CASBAH: a searchable database of caspase substrates. AB - Apoptosis is coordinated by members of the caspase family of aspartic acid specific proteases. Other members of this protease family also play essential roles in inflammation where they participate in the maturation of pro inflammatory cytokines. To date, almost 400 substrates for the apoptosis associated caspases have been reported and there are likely to be hundreds more yet to be discovered. Thus, the fraction of the proteome that is degraded (the degradome) by caspases during the demolition phase of apoptosis appears to be quite substantial. Despite this, we still know surprisingly little concerning how caspases provoke some of the signature events in apoptosis, such as membrane phosphatidylserine externalization, cellular retraction, chromatin condensation and apoptotic body production. The inflammatory caspases appear to be much more specific proteases than those involved in apoptosis and only two confirmed substrates for these proteases have been described to date. Here, we have compiled a comprehensive list of caspase substrates and describe a searchable web resource (The Casbah; www.casbah.ie) which contains information pertaining to all currently known caspase substrates. We also discuss some of the unresolved issues relating to caspase-dependent events in apoptosis and inflammation. PMID- 17273175 TI - Aspects of the dental vocational training experience in the South East of England. AB - AIM: To determine aspects of the 'lived experience' of dental vocational training (VT) for vocational dental practitioners (VDPs) and their trainers. DESIGN: A qualitative study: semi-structured interviews were conducted with the participants halfway through VT and once the VT year had been completed. PARTICIPANTS: Two consecutive cohorts of 13 and 22 VDPs and their trainers. RESULTS: The experience of VT for the VDPs and their trainers is presented together with a model of VDP progression through the VT year. CONCLUSION: VT is a success for VDPs and their trainers. Not one VDP would have wanted to enter general practice without VT. With very few exceptions the trainers considered VDPs capable of independent practice, post VT. Trainers were considered as positive role models by their VDPs. VT facilitates the transition of novice dentists into competent practitioners. PMID- 17273176 TI - Provision of domiciliary dental care by Scottish dentists: a national survey. AB - Demand for domiciliary dental care is increasing as a result of a growing population of elderly and functionally dependent patients, legislative pressure and an increasingly dentate population. OBJECTIVE: To estimate the amount and types of dental care currently being undertaken on a domiciliary basis in Scotland and to examine the barriers to the provision of such care. METHOD: A descriptive study, involving a self-administered postal questionnaire was employed. All general dental practitioners (n = 1,995) and community dental officers (n = 200) in all Health Board areas across Scotland were included in the postal survey. Data were analysed in SPSS. RESULTS: The valid response rate was 66%. Sixty-seven percent of dentists undertook at least one domiciliary visit per year, mainly for elderly patients. Prosthetic treatment was undertaken most commonly. Other types of treatment were delivered mainly by the community dental service. Many dentists did not carry a light source or emergency essential drugs and half of the dentists overall were not confident to administer emergency drugs. Significant problems were identified in relation to the packaging and carriage of contaminated instruments and clinical waste. Of those respondents not providing domiciliary care, 19% stated that they would never consider doing so. Barriers to the provision of domiciliary care included time, poor remuneration, concerns about infection control, emergency drugs and lack of suitable equipment, and the difficulties of carrying equipment. CONCLUSION: Staff training, specialist equipment and new service models for the delivery of domiciliary care are required. PMID- 17273174 TI - The N-terminal conformation of Bax regulates cell commitment to apoptosis. AB - The Bcl-2 protein Bax normally resides in the cytosol, but during apoptosis it translocates to mitochondria where it is responsible for releasing apoptogenic factors. Using anoikis as a model, we have shown that Bax translocation does not commit cells to apoptosis, and they can be rescued by reattachment to extracellular matrix within a specific time. Bax undergoes an N-terminal conformational change during apoptosis that has been suggested to regulate conversion from its benign, cytosolic form to the active, membrane bound pore. We now show that the Bax N-terminus regulates commitment and mitochondrial permeabilisation, but not the translocation to mitochondria. We identify Proline 13 within the N-terminus of Bax as critical for this regulation. The subcellular distribution of Proline 13 mutant Bax was identical to wild-type Bax in both healthy and apoptotic cells. However, Proline 13 mutant Bax induced rapid progression to commitment, mitochondrial permeabilisation and death. Our data identify changes in Bax controlling commitment to apoptosis that are mechanistically distinct from those controlling its subcellular localisation. Together, they indicate that multiple regulatory steps are required to activate the proapoptotic function of Bax. PMID- 17273177 TI - A controlled release pilocarpine buccal insert in the treatment of Sjogren's syndrome. AB - OBJECTIVES: To assess the efficacy of a novel hydrogel polymer buccal insert containing 5 mg pilocarpine in releasing the pilocarpine in a controlled fashion over a three hour period, and to assess the effects of this on quantitative tear and saliva production and the acceptability of the insert to the patient. DESIGN: This was an open, uncontrolled pilot study for which Ethics Committee approval was obtained prior to starting. Hydrogel buccal inserts containing 5 mg pilocarpine were used three times a day for seven days. SETTING: The Department of Oral Medicine, Glasgow Dental Hospital & School. SUBJECTS: Eight patients with Sjogren's syndrome. MAIN OUTCOME MEASURES: Changes over baseline in (1) Schirmer test, (2) whole saliva flow rate, (3) oral comfort score (VAS), (4) ocular comfort score (VAS), (5) patient acceptability. RESULTS: The buccal inserts successfully released in excess of 85% of their 5 mg pilocarpine load over three hours. There was a general improvement in oral and ocular comfort scores assessed by visual linear analogue scale, and saliva and tear production generally increased. The inserts were well tolerated by all patients except one (who wore dentures). Adverse events were few and none was serious. CONCLUSION: This novel form of buccal pilocarpine delivery demonstrated potential for use in treating patients with Sjogren's syndrome. PMID- 17273178 TI - Post-operative pain and use of analgesic agents in children following intrasulcular anaesthesia and various operative procedures. AB - AIM: To characterise post-operative pain (PDP) and use of analgesic agents in children. METHODS: The study consisted of 472 children, who received routine dental treatment. Teeth were anaesthetised by a computerised delivery system, either intrasulculary (CDS-IS) or by local infiltration (CDS-IF). Information regarding post-operative pain and use of analgesic agents was obtained by a telephone call within 24 hours after treatment. RESULTS: The overall incidence of PDP was 38%. 60.9% of the children who experienced PDP were given an analgesic agent. Incidence and severity of pain were significantly associated with type of dental procedure. The highest incidence was found after root canal treatment (62.5%) and preformed crowns (60.8%). A higher incidence of PDP was found in teeth with history of pain or abscess as compared to teeth with restoration or caries (p <0.01). Incidence of pain was not associated with restoration material, extension, depth or type (occlusal vs proximal) of restoration, multiple restoration, gender, mode of CDS anaesthesia, or effectiveness of anaesthesia during dental treatment. Analgesic drugs were given mainly after preformed crowns, root canal filling and extractions. CONCLUSIONS: PDP and analgesic use in children is common, especially after root canal filling, preformed crowns and extractions. CDS-IS is not associated with increased PDP. PMID- 17273179 TI - Mouth ulcers: a study of where members of the general public might seek advice. AB - OBJECTIVE: To investigate where the public seek advice about mouth ulcers and to what extent the public approach the community pharmacy for advice. SUBJECTS AND METHODS: One thousand members of the general public were randomly chosen and surveyed throughout the day in the main shopping streets of two towns in Israel, Haifa and Tel Aviv. All participants were presented with four standard verbal questions designed to identify reactions to and past experience of mouth ulcers. All responses were recorded immediately on to data sheets and transferred to a computer for analysis of frequencies and percentages and Chi-square analysis. RESULTS: Nearly one third of those surveyed admitted to a history of mouth ulceration. The vast majority (66-69%) would first approach their general medical practitioner for advice, 13-17% would first approach a general dental practitioner, and only a small minority of the public (4-10%) would first approach the community pharmacy. Lay persons could not distinguish an ulcer with features that would strongly suggest a malignant neoplasm from other types of mouth ulcer. CONCLUSIONS: The dental profession needs to collaborate more closely with the medical and pharmaceutical professions in order to offer patients better access to information and care. PMID- 17273180 TI - Infective endocarditis and dentistry: the legal basis for an association. AB - OBJECTIVES: The objectives of this study were to determine on what evidence infective endocarditis (IE) could be legally linked to dental treatment. METHOD: The records of 319 legal cases involving dental treatment as the probable cause of IE were analysed. The medical history, type of dental operation, and whether antibiotic prophylaxis was provided were noted. The time taken for the onset of symptoms (incubation period) and hospitalisation was calculated. The identity of the infecting micro-organism was investigated and it was also noted whether litigation was successful for the patient. RESULTS: A total of 83 patients were successful in legally linking dental treatment to the onset of infective endocarditis. In all successful cases there was a short incubation period (circa nine days) and in 80 of the patients an oral Streptococcus was isolated. The dental operations included exodontia (28), scaling (29), endodontics (12) and minor oral surgery (11). CONCLUSIONS: Dental treatment was deemed to be the probable cause of IE in 26% of patients who sought litigation. In the majority of legal cases clinicians did not follow recognised guidelines or keep adequate clinical notes. The three main factors which link dental procedures legally were the dental operation, the isolation from the blood of an oral micro-organism and a short incubation period. PMID- 17273181 TI - Adenovirus 5 vector genetically re-targeted by an Affibody molecule with specificity for tumor antigen HER2/neu. AB - In order to use adenovirus (Ad) type 5 (Ad5) for cancer gene therapy, Ad needs to be de-targeted from its native receptors and re-targeted to a tumor antigen. A limiting factor for this has been to find a ligand that (i) binds a relevant target, (ii) is able to fold correctly in the reducing environment of the cytoplasm and (iii) when incorporated at an optimal position on the virion results in a virus with a low physical particle to plaque-forming units ratio to diminish the viral load to be administered to a future patient. Here, we present a solution to these problems by producing a genetically re-targeted Ad with a tandem repeat of the HER2/neu reactive Affibody molecule (ZH) in the HI-loop of a Coxsackie B virus and Ad receptor (CAR) binding ablated fiber genetically modified to contain sequences for flexible linkers between the ZH and the knob sequences. ZH is an Affibody molecule specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) that is overexpressed in inter alia breast and ovarian carcinomas. The virus presented here exhibits near wild-type growth characteristics, infects cells via HER2/neu instead of CAR and represents an important step toward the development of genetically re-targeted adenoviruses with clinical relevance. PMID- 17273182 TI - Local delivery system of cytotoxic agents to tumors by focused sonoporation. AB - Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. The cytotoxicity of bleomycin (BLM) was investigated using flow-cytometric analysis and Hoechst's staining in vitro assay systems. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9 22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. Histological analysis revealed that the cytotoxic effect was mainly apoptosis. We previously reported that the cytolethal distending toxin B (cdtB) from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporation-induced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo. These findings suggest that local administration of cytotoxic agents with sonoporation is a useful method for molecular cancer therapy. PMID- 17273185 TI - Safe harbor. PMID- 17273183 TI - New strategy for the identification of squamous carcinoma antigens that induce therapeutic immune responses in tumor-bearing mice. AB - This study describes a new strategy for the identification of squamous carcinoma antigens tumor-associated antigens (TAA). The antigens were discovered by comparing microarrays of squamous carcinoma vaccines highly enriched for immunotherapeutic cells with non-enriched vaccines. The vaccines were prepared by transferring sheared genomic DNA fragments (25 kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 mouse origin (H-2(d)) into LM fibroblasts (C3H/He origin, H-2(k)). The transferred tumor DNA segments integrate spontaneously into the genome of the recipient cells, replicate as the cells divide and are expressed. As only a small proportion of the transfected cell population was expected to have incorporated DNA segments that included genes specifying TAA (the vast majority specify normal cellular constituents), a novel strategy was employed to enrich the vaccine for TAA-positive cells. Microarrays were used to compare genes expressed by enriched and non-enriched vaccines. Seventy-five genes were overexpressed in cells from the enriched vaccine. One, the gene for Cytochrome P450 (family 2, subfamily e, polypeptide 1) (Cyp2e1), was overexpressed in the enriched but not the non-enriched vaccine. A vaccine for squamous carcinoma was prepared by transfer of a 357 bp fragment of the gene for Cyp2e1 into the fibroblast cell line. Robust immunity, sufficient to result in indefinite survival, was induced in tumor-bearing mice immunized with cells transfected with this gene fragment. PMID- 17273184 TI - Targeting of products of genes to tumor sites using adoptively transferred A-NK and T-LAK cells. AB - Despite successes in animals, cytokine gene expression selectively in human tumors is difficult to achieve owing to lack of efficient delivery methods. Since interleukin (IL)-2-activated natural killer (A-NK) and phytohemagglutinin and IL 2 activated killer T (T-LAK) cells, as previously demonstrated, localize and accumulate in murine lung tumor metastases following adoptive transfer, we transduced them to test their ability to deliver products of genes selectively to tumors. Assessments of transduction efficiency in vitro demonstrated that adenoviral transduction consistently resulted in high (>60%) transduction rates and substantial expression of transgenes such as GFP, Red2, luciferase, beta galactosidase and mIL-12 for at least 4 days. In vivo experiments illustrated that Ad-GFP transduced A-NK and Ad-Red2 (RFP) transduced T-LAK or mIL-12 transduced A-NK cells localized 10-50-fold more or survived significantly better than mock transduced cells, respectively, within lung metastases than in the surrounding normal lung tissue. Most importantly, mIL-12 transduced A-NK cells provided a significantly greater antitumor response than non-transduced A-NK cells. Thus, adoptive transfer of A-NK and T-LAK cells represents an efficient method for targeting products of genes to tumor sites. PMID- 17273186 TI - The evolution of childbirth educator to perinatal educator. AB - The field of childbirth education has been slowly expanding its base to that of perinatal education over the last decades. This is a call to define the scope of a comprehensive perinatal education program and the skills of a perinatal educator. PMID- 17273187 TI - Exercise during the childbearing year. AB - Many women wish to continue to pursue an active lifestyle during pregnancy, while the pregnancy itself may provide the motivation for other more sedentary women to begin an exercise program for the sake of improved health/fitness. Also, female competitive athletes, upon becoming pregnant, may wish to continue sports performance and require careful monitoring to assure maternal-fetal safety. This review is designed to assist the perinatal educator who is in the position to advise the pregnant patient on the risks and benefits of physical activity during the childbearing year and provide suggestions for developing individualized exercise programs. PMID- 17273188 TI - The history of lamaze continues: an interview with elisabeth bing. AB - Elisabeth Bing-physiotherapist, childbirth educator, and cofounder of the American Society for Psychoprophylaxis in Obstetrics (now Lamaze International) is well known to most childbirth educators in the United States. She has been a true pioneer in the education of parents for pregnancy and birth. Her book, Six Practical Lessons for an Easier Childbirth, served to guide many parents and childbirth educators in the use of the Lamaze Method for labor and birth. She has prepared a countless number of parents for their birth experience in both her hospital classes in the 1950s and 1960s and in her private classes in the "studio" of her New York City apartment building, where she began teaching in the 1960s and continues to teach today. Elisabeth is beloved by all those who have had the opportunity to meet her or work with her. She has created a legacy that will continue for decades to come. PMID- 17273190 TI - The polomeno family intervention framework for perinatal education: preparing couples for the transition to parenthood. AB - Couples face many challenges as they transform themselves from dyad to triad. For some couples, these challenges are life-enriching experiences, while for others, chaos ensues, potentially leading to separation and divorce. The transition to first-time parenthood, even for well-functioning couples, is fraught with potential disorganization. At the same time, it provides opportunities for simultaneous self-growth and conjugal enrichment. What role can perinatal educators play in preparing couples to deal with the changes associated with this transition? To answer this vital question, the author presents her conceptualization of perinatal education as a primary family intervention framework during the perinatal period. PMID- 17273189 TI - Professionally mediated peer support and early breastfeeding success. AB - Social support interventions that incorporate professionally mediated peer support (PMPS) for improved breastfeeding outcomes were compared with no special breastfeeding support. Fifty-five breastfeeding mothers participated. The breastfeeding outcomes of duration, completeness, satisfaction, and exclusive breastfeeding were compared at 6 weeks postpartum among an experimental group that received PMPS, and among younger community (YC) and older community (OC) groups that received no special breastfeeding support. The PMPS group exclusively breastfed for a significantly longer duration than the YC group. At 6 weeks, mothers in both community groups who had weaned were significantly less satisfied with their breastfeeding experiences than the mothers who were still nursing their babies. Professionally mediated peer support can improve the early breastfeeding outcomes of duration of exclusive breastfeeding and satisfaction with breastfeeding. PMID- 17273191 TI - Childbirth educators' legal and ethical responsibilities to women in labor. AB - In answer to a reader's question, the author of this column addresses the legal and ethical responsibilities of a Lamaze Certified Childbirth Educator who agrees to attend her students' drug-free delivery. PMID- 17273192 TI - Kay's Perinatal Krossword Puzzle JPE 9, 1. PMID- 17273194 TI - A Woman's Litany of Cries in the Night. PMID- 17273193 TI - Any questions? AB - In spite of their best efforts, nurses still get asked some of the most bizarre questions. PMID- 17273196 TI - Jami's Song. PMID- 17273195 TI - Moments fleeting. PMID- 17273197 TI - Soul to soul. PMID- 17273198 TI - Birth environments. AB - Childbirth educators can actively participate in the birth environment and, thus, greatly contribute to the re-emerging childbirth movement. PMID- 17273199 TI - The birth plan revisited. AB - In answer to a reader's question, the author of this column discusses moving birth plans beyond a check list of options to a plan of evolving confidence, support-building, and comfort. PMID- 17273200 TI - "The birthing from within holistic sphere": a conceptual model for childbirth education. AB - An expanded conceptual model of childbirth education is offered, proposing the benefits of balancing informative teaching processes with creative, experiential, introspective learning processes for parents. The application of these two teaching dimensions to exploring four different perspectives of birth (the mother's, the father's, the baby's, and the culture's) is discussed, along with examples from "Birthing From Within" classes. Implications for current practice and the evolving role of childbirth educator are noted. PMID- 17273201 TI - Alternative strategy to decrease cesarean section: support by doulas during labor. AB - This research was conducted in a public general hospital in Mexico City, Mexico. The objective was to evaluate efficacy of the support given by a doula during labor to reduce cesarean rate. From March 1997 to February 1998, a group of 100 pregnant women were studied. These women were at term, engaged in an active phase of labor, exhibited 3 cm. or more cervical dilatation, were nuliparous, had no previous uterine incision, and possessed adequate pelvises. The group was randomly divided into two subgroups comprising 50 women, each: The first subgroup had the support of a childbirth educator trained as a doula, while the second subgroup did not have doula support. Measurements were recorded on the duration of labor, the use of pitocin, and whether or not the birth was a vaginal birth or cesarean section. Characteristics and gestational age were similar in both groups. Results confirmed that support by doulas during labor was associated with a significant reduction in cesarean birth and pitocin administration. There was a trend toward shorter labors and less use of epidurals. The results of this study showed, as in other trials measuring the impact of a doula's presence during labor and birth, that doula support during labor is associated with positive outcomes that have physical, emotional, and economic implications. PMID- 17273202 TI - Marginalizing women: images of pregnancy in williams obstetrics. AB - This research analyzes the historical development of the medical construction of the pregnant body in 17 of 20 editions of Williams Obstetrics, an obstetrical textbook published continually from 1904 to 1997. Examination of the visual imagery of these works produced three key findings. First, depictions of the healthy or "normal" pregnant body are virtually absent throughout the series. Second, visual depictions of women's full bodies adhere to a race-based hierarchy of presentation. Finally, the fundamental discourse about pregnant and female bodies communicated to physicians (primarily) by these images is one of pathology and fragmentation. We conclude that the resulting social and medical construction of the pregnant and female body presented in the Williams series is one of disembodiment, abjection, and ultimately marginality. These findings support recent feminist research that criticizes both the increasing erasure of the person of the women from the medical interpretation of pregnancy and the concomitant decrease in women's perceived sense of empowerment as pregnant beings. PMID- 17273203 TI - Evaluation of a pilot project: preparenthood and pregrandparenthood education. AB - A pilot project in expanding perinatal education is presented in this article. The author has experimented with a series of group sessions on the introduction to the transition to parenthood for couples who are either engaged or recently married. Such couples, if introduced to the changes associated with the transition to parenthood at a point of development in the commitment process, may increase their chances of weathering the turbulence that is often a part of the transition. The potential grandparents are part of the process since they are usually an important source of social support. Preparenthood and pregrandparenthood education is a useful extension of perinatal education for the beginning of this century. PMID- 17273204 TI - The Door's Perinatal Program for Pregnant and Parenting Teens. AB - The perinatal program for urban youth at The Door, located in New York City, provides accessible, comprehensive, high-quality prenatal services to pregnant teens. Through a holistic, family-centered, youth-development approach, the program seeks to counteract the adverse medical risks and psychosocial consequences of early childbirth and child rearing in order to improve the immediate and long-term futures of the mother and her new family. The Door's services are presented, along with a description of the agency's service model and an analysis of 100 pregnant teens enrolled in its perinatal program. PMID- 17273205 TI - Programs for adolescent mothers are needed. AB - This column reviews the article "The Door's Perinatal Program for Pregnant and Parenting Teens" [Journal of Perinatal Education, 9(2), 39-46] and acknowledges the need for innovative programs to help reduce the risks associated with adolescent pregnancy and teen births. PMID- 17273206 TI - Alarming racial differences in maternal mortality. AB - In this column, the author reviews statistics that reflect the disparity of maternal mortality rates among black, nonwhite, and white women. PMID- 17273207 TI - Humor doulas. AB - Laughter at professional health care conferences may be the best medicine. PMID- 17273208 TI - Transitions. PMID- 17273209 TI - Celebrate being a childbirth educator. AB - Some of the many reasons to celebrate the work of childbirth educators include Lamaze International's upcoming 40th anniversary, an impressive history of dedicated people who first pioneered childbirth education, and the active role childbirth educators continue to play in promoting consumer advocacy in health care. PMID- 17273210 TI - Really teaching lamaze: what about pushing? AB - A reader is justifiably puzzled when a Lamaze childbirth educator tells her that directed pushing is the Lamaze way. The author of this column discusses second stage in the context of normal, natural birth, guidelines for pushing, evidence based practice, and strategies to access and incorporate evidence into practice. PMID- 17273211 TI - Presenting relaxation techniques to pregnant adolescents. AB - Teens present a unique challenge for the childbirth educator. A committed educator must find creative teaching strategies that will ease an adolescent's tension and provide a safe environment where a teen can "own" the message of her body's ability to give birth. The author of this column presents one of her own strategies for teaching relaxation techniques to adolescents. PMID- 17273212 TI - Apgar Scores: Examining the Long-term Significance. AB - The Apgar scoring system was intended as an evaluative measure of a newborn's condition at birth and of the need for immediate attention. In the most recent past, individuals have unsuccessfully attempted to link Apgar scores with long term developmental outcomes. This practice is not appropriate, as the Apgar score is currently defined. Expectant parents need to be aware of the limitations of the Apgar score and its appropriate uses. PMID- 17273213 TI - Perspectives on learning for childbirth educators. AB - This continuing education module reviews the uses of ways of knowing and ways of learning to assist the childbirth educator become a master teacher who facilitates the growth of the learner. PMID- 17273214 TI - Effect of maternal prenatal smoking on infant growth and development of obesity. AB - It is well-documented that infants born to smoking mothers weigh less at birth than infants born to nonsmoking mothers. The purpose of this study was to investigate the influence of prenatal smoking on the development of later infant obesity. Evidence suggests prenatally smoke-exposed infants catch up in weight by age 6 months, although results of this accelerated growth are inconsistent across the body of research literature. In this descriptive study of 630 infants, catch up growth rate continued and smoke-affected infants were more likely to be obese than their nonsmoke-affected counterparts from age 6 to 14 months. The findings of this study provide insight about the potential effects of maternal prenatal smoking on the risk of early obesity. This paper also discusses the importance of assisting mothers to cease smoking while pregnant. PMID- 17273216 TI - "Pinklining" and childbirth education. AB - Domestic violence in a family is often found to have begun during a pregnancy. "Pinklining" is denying insurance to victims of domestic violence. Both domestic violence and pinklining are concepts with which the childbirth educator should be familiar, including the relevant laws and resources. PMID- 17273215 TI - You can make a difference. AB - Inaccuracies, injustices, bad advice, and insensitivity are irritating. Most of us feel powerless to do anything about such situations or don't have the time or energy to try to make changes. A strategy is described that allows the author to address her concerns. Examples are given of changes that occurred because of her efforts through writing letters. Childbirth educators become aware of policies and situations that need change; as advocates, they are encouraged to take the risk and enjoy the challenge of creating change. PMID- 17273217 TI - Breastfeeding videos offer reliable information and vivid images. PMID- 17273219 TI - Kay's Perinatal Krossword Puzzle JPE 9 - 3. PMID- 17273218 TI - In the Patient's Best Interest: Informed Consent or Protection from the Truth? AB - In response to a reader's essay, the author of this column states that physicians must legally and ethically provide expectant parents with information about their risks and options. It is not acceptable to withhold information or simply not to bother to relate information. Childbirth educators can help promote patient autonomy in health decision-making. PMID- 17273221 TI - Labor day song. PMID- 17273222 TI - Bad hair day. PMID- 17273220 TI - Remember what? AB - Childbirth educator humorously describes the perils of an aging instructor attempting to stay current with the latest infant-related equipment. PMID- 17273223 TI - Sharing your wisdom: the perinatal author. AB - Perinatal educators are encouraged to consider the scope of their impact on launching new families by sharing their wisdom through authorship. PMID- 17273224 TI - Respect in the perinatal experience. AB - Perinatal educators wish to respect all parties in the perinatal experience. To accomplish this, some may need to learn and practice ways to express feelings of respect. Respect can be written into policy or procedure and is implicit in personal interaction. While all the possible ways to demonstrate respect cannot be listed and passed along, principles of respect can be offered for guidance. PMID- 17273225 TI - Empowering Teens: Real Talk about Real Life. AB - The author presents three worksheets that have been found to be useful in working with pregnant adolescents. Use of these worksheets is discussed. PMID- 17273227 TI - Sex and Pregnancy: A Perinatal Educator's Guide. AB - This article is a continuation in the author's growing series of articles on intimacy and sexuality in the transition to parenthood and its relationship with perinatal education. So many couples in the author's perinatal education practice feel that health professionals are uncomfortable discussing sex and pregnancy. Indeed, the couples have so many questions and concerns regarding this subject; they are seeking answers so that they may better understand and cope with the changes in this aspect of their relationship. Perinatal education group encounters or special sessions are the ideal setting to discuss intimacy and sexuality during pregnancy. The objectives of this article are to provide the perinatal educator with content for the group sessions and tools for teaching strategies and activities. PMID- 17273226 TI - Creating Consistency and Control Out of Chaos: A Qualitative View of Planned Pregnancy during Adolescence. AB - Adolescent pregnancy can have devastating effects for both mother and child. However, little is known about the experience of planned pregnancy among adolescents. This paper presents an in-depth analysis of themes identified in a previous study of the experience of planned adolescent pregnancy. The experience of planning a pregnancy during adolescence consists of typical adolescent behavior in that these girls demonstrated the need for control, invulnerability, and a present focus to their lives. In addition to this typical behavior, a component manifests itself in which adolescent girls make reproductive health choices to gain control. By establishing a level of control over their hectic and stressful lives, they are able to add meaning to their lives. The need for consistency and control seem to be linked, because many of the adolescent girls' statements reflected dimensions of both concepts. This initial, descriptive study can be used to further explore adolescent pregnancy and to develop interventions that might assist these girls to lead healthy lives. PMID- 17273228 TI - Developing a family-centered, hospital-based perinatal education program. AB - The development of a family-centered, comprehensive perinatal education program for a large, urban hospital system is described. This program was developed in conjunction with the building of a new women's center and, although the authors were fortunate that several opportunities for educational program development were linked to this project, many of the steps taken and the lessons learned can be helpful to anyone desiring to develop a similar program. This article relates perinatal education to the principles of family-centered maternity care, outlines the criteria for a quality educational program, gives rationale for this type of program development, and offers practical suggestions for starting or enhancing a perinatal education program within a hospital system. PMID- 17273229 TI - Even a "princess of a program" may face challenges. AB - Commentators discuss the merits of the article "Developing a Family Centered, Hospital-Based Perinatal Education Program" [Journal of Perinatal Education, 9(4), 28-39]. They also point out the challenges of developing, implementing, and maintaining a comprehensive, family-centered perinatal education program in urban and rural hospitals. PMID- 17273230 TI - Why natural childbirth? AB - A reader asks for help in answering the question "Why natural childbirth?" Understanding the simple story of normal, natural birth, what helps and what sabotages nature's plan for birth, and the appropriate use of interventions are discussed and form the foundation for coming to the conclusion that nature's plan makes sense. Women are inherently capable of giving birth, have a deep, intuitive instinct about birth, and, when supported and free to find comfort, are able to give birth without interventions and without suffering. PMID- 17273232 TI - Nature's Force. PMID- 17273231 TI - Pms. AB - Sometimes, biting off a head can be just the right cure for PMS blues. PMID- 17273233 TI - Research and public policies help advance the benefits of breastfeeding and natural childbirth. AB - As more and more research recognizes the benefits of breastfeeding and natural childbirth, public policy steps up its efforts to protect these benefits. PMID- 17273234 TI - Really teaching lamaze: evidence-based practice. AB - In this column, a reader identifies the importance of accurate, up-to-date information in making informed decisions. She is shocked to find that the Lamaze classes she observes are not evidence-based. Evidence-based practice is described, and examples of the use of best evidence in childbirth classes are discussed. The implications for childbirth education are explored. PMID- 17273235 TI - Back pain/discomfort in pregnancy: invisible and forgotten. AB - This paper is a comprehensive literature review of original research on the nature of back pain/discomfort in pregnancy. The causes of back pain/discomfort in pregnancy are reviewed and discussed, and the clinical manifestations and implications are explored. This analysis revealed that approximately 50% of pregnant women experience back pain/discomfort with little or no intervention from their health care providers. Thus, back pain/discomfort in pregnancy seems to be invisible and forgotten in contemporary antenatal care. Evidence-based guidelines are provided for both women and health professionals as a way of increasing attention to the prevention of unnecessary back pain/discomfort during pregnancy. PMID- 17273236 TI - The history of lamaze continues: an interview with sunnye strickland. AB - Although the most publicized beginnings of the Lamaze method in this country took place in the New York City area in the 1950s and 1960s, change was taking place even earlier in other parts of the United States as well, for women everywhere were eager to be educated and awake for their birth experiences. One of the early leaders of the "natural childbirth movement" in Colorado, Wyoming, and Oklahoma from the late 1940s through the early 1960s was Sunnye Strickland. Strickland began her career as a labor and delivery nurse, became a devoted advocate of prepared childbirth as a result of her own birth experiences, and embraced the philosophy of the psychoprophylactic method after visiting Dr. Pierre Vellay in Paris. She then became a faculty member with the American Society of Psychoprophylaxis in Obstetrics (ASPO/Lamaze, now Lamaze International, Inc.) and eventually a certified nurse-midwife. Her professional story spans five states, several countries, and 46 years, with a rich variety of experiences in which she was a change agent, educator, and active leader in the childbirth education movement. PMID- 17273237 TI - Breastfeeding Prevalence among an Alaskan Inupiat Eskimo Population. AB - Breastfeeding provides valuable immunologic, nutritional, and psychological advantages to infants and is the most desirably complete diet for the infant during the first 6 months of life. The purpose of this exploratory study was to determine the prevalence of breastfeeding in a group of Alaskan Inupiat Eskimos, who live in northern Alaska. A convenience sample of 36 women making up three age cohorts was utilized (women ages 18 to 25, N=11; ages 26 to 40, N=14; ages 41 to 60, N=11). Data collected from these women on their choice of infant-feeding method contributed to measuring the prevalence of breastfeeding. Prevalence was also measured by categorizing the children of these women into three age groups and further classifying them as to how they were fed when they were infants. Statistical analysis was performed utilizing 95% confidence intervals. Results revealed that, in this sample and over the past 20 years, a substantial decline has occurred in the percentage of Inupiat infants exclusively breastfeeding for 6 months or longer. Data also indicated a downward trend in the percentage of mothers between the ages of 26 and 39 who initiate breastfeeding; however, among the mothers aged 18 to 25, data reflected a rising trend. PMID- 17273239 TI - Papers presented at the 8th international conference of maternity care researchers. AB - This column provides a brief overview of some of the papers and presentations offered at the 8th International Conference of Maternity Care Researchers, held September 2000 at the University of Glasgow in Scotland. PMID- 17273238 TI - Maternal-newborn nursing: thirteen challenges that influence excellence in practice. AB - The purpose of this paper is to review the research and discuss 13 challenges that currently influence excellence in maternal-newborn nursing practice. Nurses working in the maternal-newborn arena are encouraged to evaluate their own practices in relation to the identified areas. The 13 identified challenges are the following: integration and expansion of midwifery and family-centered models of care, reduction in the use of unnecessary or questionable-benefit technology, patient and family teaching, the questionable need for a normal newborn nursery, integration of research into practice, further development of genetic technology and counseling, computer technology as an adjunct to prenatal care and birth, the need for comprehensive breastfeeding education and support, prenatal care on a continuum beginning as women's health promotion, health promotion beyond the postpartum period, culturally competent care, health insurance coverage for all women and children, and an undereducated work environment. PMID- 17273240 TI - The Surgeon General's "Blueprint for Action on Breastfeeding". PMID- 17273241 TI - Can any childbirth educator use the lamaze trademark? AB - A Lamaze Certified Childbirth Educator asks about the use of the name Lamaze, which is a licensed (trademark) name. A trademark is a mark of authenticity. It protects both the users and the consumers. Penalty for unauthorized use (e.g., by a childbirth educator who is not an LCCE) can be substantial. PMID- 17273243 TI - My voice. PMID- 17273242 TI - And the OSCAR goes to ... AB - Perinatal care providers function around the clock, perhaps overassessing themselves and others. PMID- 17273244 TI - The synchrony of mother-infant needs. AB - Growing evidence continues to demonstrate the benefits infants derive from breastfeeding, and the connection to natural births and breastfeeding is made apparent; however, mothers may misunderstand. They may mistakenly believe they must sacrifice in order to give their infants the best start in life. Childbirth educators can help mothers understand how they, too, may personally benefit from natural childbirth and breastfeeding. These mother-infant needs are not competitive; instead, they are synchronous. PMID- 17273245 TI - Questions from Our Readers Commentary on Lamaze International's Statement on Induction. AB - Lamaze International recommends that "pregnant women neither choose nor agree to be induced unless there is a true medical indication for induction." This commentary discusses the recommendation and its implications for the practice of childbirth education. PMID- 17273246 TI - Lamaze international expands to Korea. PMID- 17273247 TI - Birth stories: a way of knowing in childbirth education. AB - Birth stories have a lasting impact on expectant mothers. The purpose of this paper is to recognize the influence of birth stories as a key component of informal communication of knowledge about childbirth for expectant mothers. The review of literature and research is related to childbirth education, anthropological thinking, and applied learning theory with foundational concepts from Vygotsky, Bruner, and Bandura. Implications for childbirth educators are included. PMID- 17273248 TI - The story of ferris urbanowski: california, here we come! AB - Although childbirth educators may not all have known her by name, the lovely redhead who was the star childbirth educator in the 1970s film The Story of Eric was a familiar face. After viewing the film numerous times in our classes, early childbirth educators all felt that we knew her. Ferris Urbanowski was an early crusader for the Lamaze method of childbirth preparation in California in the 1960s. She worked to convince physicians in the Los Angeles area of the merits of the method, to establish classes for expectant parents, and to start a chapter of ASPO (now, Lamaze International, Inc.) in Los Angeles. Her book about yoga illustrated how additional methods of relaxation could benefit pregnant women. Today, Urbanowski attributes her past involvement in childbirth education to her current professional role as a teacher and counselor in the field of stress reduction at the Stress Reduction Clinic at the University of Massachusetts Medical Center. PMID- 17273249 TI - Effects of a prenatal care intervention on the self-concept and self-efficacy of adolescent mothers. AB - The objective of this study was to examine changes in self-concept and self efficacy during the childbearing year among adolescent mothers (defined as young mothers up to age 20) who were involved in a behavioral intervention. Subjects included a sample of 282 urban, pregnant adolescents (94% African American, 4% white, 2% other). The Tennessee Self-Concept Scale (TSCS) was used to measure self-concept. A scale to measure the self-efficacy of the adolescent mother during the childbearing year was developed and evaluated. Questionnaires were administered during intake for prenatal care and in the postpartum period. In the larger study, the intervention was a peer-centered, mastery modeling intervention designed to increase self-efficacy, improve self-concept, and improve long- and short-term perinatal outcomes. The results in this portion of the data showed that self-concept increased significantly for young women in the experimental group but did not change significantly for young women in the control group. Changes were noted in the TSCS for overall self-concept as well as for several subscores, including identity, self-satisfaction, behavior, the personal self, the family self, and the social self. However, differences between groups did not reach significance once age, parity, site, and time were accounted for, except on TSCS subscales of identity and personal self. Between intake for prenatal care and postpartum, self-efficacy changed significantly for both the experimental and the control groups. Both groups increased in self-efficacy for labor and delivery and decreased in self-efficacy for infant care. In this group of mostly African American teens, peer support and small group care demonstrated positive effects on self-concept. Professional and peer interactions were equally associated in intervention and nonintervention groups with regard to self-efficacy. PMID- 17273250 TI - Mothers' perceptions of benefits of perinatal loss support offered at a major university hospital. AB - This qualitative research investigated the perception of mothers regarding hospital support after perinatal loss. Twelve in-depth interviews demonstrated that the mothers recalled the circumstances of the loss. Most identified the hospital's support services and made comments on aspects of hospital support as influential in grief recovery. Most interviewees considered themselves somewhat recovered from the loss. PMID- 17273251 TI - Managing violence. AB - Childbirth educators are in a unique position to offer individuals and families a helpful amount of resource information on violence prevention and awareness. Internet-based resources on managing violence are especially abundant. Educators can learn from these web sites and pass along the information to their class participants. PMID- 17273252 TI - Birth and death: opportunities for self-transcendence. AB - One thing that is often absent in childbirth education classes is a discussion of the spiritual aspect of giving birth. Birth offers women a wonderful opportunity to awaken their spirituality. Natural childbirth, in particular, has the potential for self-transcendence, offering an even greater appreciation for the miracle of life. The normal, natural pain in labor can challenge the core of one's being-it is a healthy sensation that provides direction for women moving through the maze of labor. The challenge of giving birth today is to develop confidence and trust in one's inner wisdom and allow nature to do its thing. When this is accomplished, a woman's body is often permeated and nourished by spiritual energy and guidance. She emerges from her labor bed with a renewed sense of her body's strength and power and with an enhanced spirituality. PMID- 17273253 TI - Adopting birth philosophies to guide successful birth practices and outcomes. AB - Research studies conducted recently in hospitals located in Switzerland and Canada reveal the importance of birth philosophies in attaining successful birth practices and outcomes. PMID- 17273254 TI - Assuring the competence of lamaze certified childbirth educators. AB - Lamaze Certified Childbirth Educators, their employers, and Lamaze International all share the responsibility of assuring the public of an educator's ongoing competence. PMID- 17273256 TI - Buckle up. AB - A childbirth educator humorously asks why there is always more information to deliver than time in which to deliver it. PMID- 17273257 TI - Labor support. PMID- 17273255 TI - Kay's Perinatal Krossword Puzzle JPE 10-2. PMID- 17273258 TI - Advocacy and reform for the birth environment. AB - Childbirth educators can become a part of reform efforts to improve maternity services by helping to create consumer demand for such services. PMID- 17273259 TI - Do birthing options really exist? AB - In this column, the author answers the question, "Is choosing to give birth naturally a realistic option in today's birth environment?" Women's choices of health care provider and place of birth are limited by the general belief that birth is safe only in the hospital and when managed by obstetric medicine. In the typical hospital environment, women rarely have access to the wide variety of comfort measures and the continuous emotional and physical support required to give birth naturally. Routine care practices further limit women's birthing options. The Coalition for Improving Maternity Services' document, the "Mother Friendly Childbirth Initiative," offers direction for creating birth environments that ensure options for women who choose to give birth naturally. PMID- 17273260 TI - Women's Evaluation of Intrapartum Nonpharmacological Pain Relief Methods Used during Labor. AB - A wide variety of pain relief measures are available to women in labor. This retrospective, descriptive survey design study examined which nonpharmacologic pain-relief techniques laboring women use most often and the effectiveness of the chosen techniques. Of the 10 nonpharmacological strategies rated by the sample (N = 46), breathing techniques, relaxation, acupressure, and massage were found to be the most effective. However, no specific technique or techniques were helpful for all participants. The results provide directions for childbirth educators in designing and implementing an effective childbirth education curriculum that assists women to have empowered birth experiences. PMID- 17273261 TI - A perinatal intervention program for urban american indians part 1: design, implementation, and outcomes. AB - High infant mortality rates among American Indians are disproportionate to state statistics for other races and higher than the national average. These findings prompted a community health center in a large Midwestern city to create and provide an American Indian infant mortality reduction project in the early 1990s. Strategies for program implementation included networking with local organizations, communicating with reservation health clinics throughout the state, educating American Indian mothers and their community about factors contributing to American Indian infant mortality, and providing individual case management to American Indian women and infants. We offer this article for three reasons: This grant project was successful, disparity in rates of infant mortality among peoples of color continues, and a paucity of information exists about the health behaviors of American Indian women. PMID- 17273262 TI - Sources of infant feeding information used by pregnant women. AB - Selecting an infant feeding method is one of the most important decisions a mother-to-be makes. Little information is available to characterize women who plan to use both formula and breast milk. In this study, 89 pregnant women indicated their anticipated feeding method and the sources and initiator of infant feeding information. No differences were found in the type of resources used by women who planned to breastfeed, formula feed, or combination feed. Women in the study were four times more likely to initiate a conversation about infant feeding methods with a family member or friend than with a health care provider. Involving these key individuals in perinatal education classes and support programs is a simple, but powerful, strategy that childbirth educators can use to promote breastfeeding. PMID- 17273263 TI - A call to action and a challenge to use a standard to measure mother-friendly birth classes. AB - In spite of the efforts of numerous organizations and individuals to offer mother friendly birth information and care in the United States, the nation remains a highly technical, low-touch birth culture with a decline in positive maternal fetal outcomes. A number of organizations and individuals came together to form the Coalition for Improving Maternity Services and to create the Mother-Friendly Childbirth Initiative (MFCI). The MFCI is a wellness model of maternity care that offers 10 evidence-based steps of care that will improve birth outcomes and reduce costs. Birth educators can use this self-assessment tool to provide the same evidence-based information. PMID- 17273264 TI - From hospital deliveries to home birth. AB - Working in a busy labor/delivery unit gave me insight into the care that my Lamaze childbirth education students would encounter. I was troubled by the number of interventions taking place. The interventions interfered with a woman's ability to work with her labor; some interventions were actually creating problems or even crises. My experiences at this hospital motivated me to become involved with home birth, restoring my belief that birth is a normal process. PMID- 17273265 TI - Current research continues to support breastfeeding benefits. AB - Lamaze International and Lamaze Certified Childbirth Educators are strong supporters of breastfeeding. This paper reviews eight recent studies that are related to breastfeeding and useful to clinicians and educators. PMID- 17273266 TI - Clarify and document your volunteer activities. AB - In order to protect themselves from the unlikely event of being sued, childbirth educators who offer volunteer services would do well to clarify their responsibilities and document their activities. PMID- 17273267 TI - New expressions. PMID- 17273268 TI - Compiled from agency for healthcare research and quality web site. PMID- 17273269 TI - Kay's Perinatal Krossword Puzzle JPE 10 - 3. PMID- 17273270 TI - Hello. Do you read me? AB - Perinatal nurse makes an effort to blend in with the high-tech world of business travel. PMID- 17273271 TI - Selected researched evidence supporting the work of launching families. AB - Research studies have been abstracted to support action items in a Blueprint for Transforming the Lives of Children, through the childbearing and early child rearing phases of family life. The abstracts relate to childbearing. Similar abstracts related to child rearing can be found at www.aTLC.org. PMID- 17273272 TI - Blueprint for transforming the lives of children. PMID- 17273273 TI - A. Consciously conceiving: encourage prospective parents to carefully consider their readiness to assume the roles and responsibilities of becoming a parent. PMID- 17273275 TI - C. Preparing for an Optimal Birth Experience: Consider All Birthplace Options, Recognizing that Birth Experiences Are Enhanced in Home, Birth Center, or Hospital Settings that Support Parents' Informed Choices for the Labor, Birthing, and Postpartum Process. PMID- 17273274 TI - B. Fostering an Optimal Womb Environment: Honor Pregnancy as a Natural Event (Not a Medical Condition) and Recognize the Importance of the Mother's Emotional, Mental, and Physical Well-being; a Safe Environment; and a Strong Support System. PMID- 17273276 TI - D. Supporting Early Postpartum Attachment: Select a Birthing Environment that Clearly Supports the Infant-Parent Attachment Process. PMID- 17273277 TI - Sisters. PMID- 17273278 TI - Lamaze Method versus Philosophy. AB - Lamaze childbirth is no longer a method; rather, it is childbirth based on a philosophy that is articulate and incorporates many methods. A new Lamaze International position paper addresses teaching the Lamaze Philosophy. PMID- 17273279 TI - Questions from our readers: commentary on "lamaze in the 21st century". AB - In response to Lamaze International's latest position paper, "Lamaze in the 21st Century," the author discusses the concept of normal birth and identifies the need for an advocacy effort in support of normal birth as the standard procedure. PMID- 17273280 TI - Lamaze International: P P-L f t 21 C. PMID- 17273281 TI - Eat, drink, and be labouring? AB - The practice of restricting oral intake during labour has been and remains controversial. Overall, the nutritional needs of labouring women are poorly understood. This literature review reveals that little evidence exists to support the general restriction of oral intake for all labouring women. Education of health professionals and pregnant women regarding intake in labour is required to encourage collaboration in the development and institution of appropriate policies in keeping with the available evidence for best practice. PMID- 17273282 TI - Prenatal depression, violence, substance use, and perception of support in pregnant middle-class women. AB - The purpose of this study was to explore the vulnerability for postpartum depression among financially, educationally, and socially advantaged middle-class women (n = 31). Twenty-nine percent reported prenatal depression, 13% reported intimate partner violence, and 22% reported concerns with partner relationships and support expectations after delivery. No illegal substances were reported; however, a past history of smoking and excessive use of caffeine was disclosed. Implications for practice focus on the need to screen and implement intervention programs for these social problems and to adopt measures as a universal standard of care for all women, regardless of demographic advantages. PMID- 17273283 TI - Sexuality issues in adolescents with a chronic neurological condition. AB - Substantial progress in the medical treatment of individuals with spina bifida (SB) has increased the numbers who survive into adolescence and adulthood. However, sexual health in this population has not received much attention. This study explored the knowledge (SB Sexuality Knowledge Scale), worries (SB Worries Scale), romantic appeal (from Harter's Self-Perception Scale), and access to sexuality information of a sample of 60 adolescents from a midwestern state. Study participants reported having sexual feelings like their peers, and they knew they could contract sexually transmitted diseases (STDs) if they were sexually active. However, only a moderate percentage was aware that women with SB are fertile, that adolescent women with SB should take a multivitamin with folic acid, and that latex-free condoms should be used by most adolescents with SB. They did not worry about their ability to make friends; however, these adolescents reported low levels of perceived romantic appeal and they worried about sexuality issues. These sexuality issues were not correlated to measures of SB neurological severity. Although over 50% reported having discussed sexuality with a health professional, 29% reported no one discussed sexuality and SB with them. Data from this study can affect the way health care providers and educators conduct sexuality education in health care and school settings. PMID- 17273284 TI - Effects of a prenatal care intervention for adolescent mothers on birth weight, repeat pregnancy, and educational outcomes at one year postpartum. AB - About one-third of adolescent mothers receive inadequate prenatal care, and babies born to young mothers are more likely to be of low birth weight. The objective of this study is to evaluate a peer-centered prenatal care program for adolescent mothers. Pregnant adolescents were randomly assigned to an experimental or control group in a mastery modeling peer-support intervention designed to improve long- and short-term perinatal outcomes. A sample of 282 urban pregnant adolescents (94% African American, 4% Caucasian, 2% other) participated in the study. Participants were recruited from five clinics located mainly in Detroit, Michigan. Participants in the experimental group received care in a small group setting and learned to perform critical measurements with a peer partner during prenatal visits. Participants in the control group received individual prenatal care in the same clinics. Outcome measures included birth weight, years of schooling completed at one year postpartum, planned and unplanned pregnancy at one year postpartum, and employment and school attendance at one year postpartum. Mothers in the experimental group had a lower rate of low birth weight (6.6% vs. 12.5%, p=0.08). The rate of unplanned pregnancy was also lower for adolescents in the experimental group (13.4% vs. 15.9%), although this difference was not statistically significant. Adolescents who participated in the intervention were more likely to have continued their education during the pregnancy and the postpartum year. The mastery modeling, peer-centered, prenatal care program produced some positive pregnancy outcomes for adolescent mothers. PMID- 17273285 TI - Complementary and alternative therapies. AB - Complementary and alternative therapies are increasingly used by many pregnant women in the United States; however, limited research is available on many therapies. The number of studies should increase with the establishment of the National Center for Complementary and Alternative Medicine by the National Institutes of Health. This column reviews recent studies of both herbal medicines and alternative therapies used in pregnancy. PMID- 17273286 TI - Making professional referrals. AB - Lamaze Certified Childbirth Educators have a duty to their clients to make referrals to qualified professionals-in this case, to an expert in nutrition, a dietician. A reasonable way to assure a quality referral is to contact the appropriate professional organization. PMID- 17273287 TI - Web site resources for high-risk families. AB - The Internet serves as an excellent resource for childbirth educators in their search for information and education to share with high-risk families who are in need of support to help them cope with complicated pregnancies. PMID- 17273288 TI - Catch this! AB - Athletically challenged prenatal educator and labor nurse finds birthing balls a rather cruel joke. PMID- 17273289 TI - The power of story. AB - In this guest editorial, the author introduces the reader to the value of stories as a source of vision and inspiration for caregiving. PMID- 17273291 TI - Can visions of natural births dance in our heads? AB - Through the observations of a childbirth educator of women who are planning epidurals, these women's vision of birth can be contrasted with a vision of the inner-strength-promoting experience that birth can be. PMID- 17273290 TI - The guests. PMID- 17273292 TI - Normal birth: two stories. AB - THE AUTHOR SHARES TWO STORIES: one of a normal birth that took place in a hospital with a nurse-midwife in attendance and another of a home birth unexpectedly shared by many colleagues. Both are told with the goal to inform, inspire, and educate. PMID- 17273293 TI - Lamaze Childbirth among the Amish People. AB - This paper is an account of the author's observation of three Amish births in 1972, one in a home and two in a hospital. This 30-year-old story illustrates normal birth among a group dedicated to "low-tech" living. Although some aspects of Amish life and birth may have changed in the past 30 years, the basic philosophy of life and birth has not. This philosophy serves as a living reminder to us that generations of women from many cultures have given birth in a similar manner. PMID- 17273294 TI - A perinatal intervention program for urban american indians part 2: the story of a program and its implications for practice. AB - This is the story of how a culturally aware staff successfully intervened with a clientele of another culture. A high infant mortality rate for American Indians in Milwaukee, WI, prompted a community health agency to initiate a program to address the problem. Efforts were made to educate the American Indian community about the importance of both prenatal and postnatal care. Part 1 of this report was published (Davis & Prater, 2001) and presented the design and implementation of the program, as well as program outcomes. Here, Part 2 describes aspects of the same program, including the personal story of a client and the results of an evaluation conducted by a three-person research team. Implications for practice are also presented. Among these are suggestions for hiring and retaining staff, locating and retaining clients, addressing cultural sensitivity, and identifying administrative actions that enhance program operation. The personal stories of two additional clients are included to illustrate the difficult reality of some clients' lives and the resulting necessity for flexibility and resourcefulness on the part of program staff. This program represents the positive impact that program workers had on the problem of American Indian infant mortality. PMID- 17273295 TI - The impact of previous perinatal loss on subsequent pregnancy and parenting. AB - The loss of any pregnancy through miscarriage, ectopic pregnancy, stillbirth, or neonatal death presents as a significant life crisis for any woman and has far reaching implications into a couple's future aspirations. Planning another pregnancy after dealing with a perinatal loss is difficult and plagued by ambivalence, doubts, and insecurities. Despite this ambivalence, a majority of women do become pregnant within a year following a perinatal loss. Four recurring issues surrounding perinatal loss and subsequent pregnancy have been identified in this literature review: the effect of the grief process on the subsequent pregnancy; parental coping mechanisms during the subsequent pregnancy; replacement or vulnerable child syndrome; and parenting issues with the subsequent live-born child. Issues surrounding anxiety as a coping mechanism during a pregnancy following a perinatal loss are documented consistently in the literature; however, less is known about the impact that a loss has on parenting behaviors with subsequent children. Further research is imperative to examine these issues in more detail so that evidence-based practices can be established and updated. Health care providers are in a unique position to assist these couples in dealing with the issues that a perinatal loss may place on subsequent pregnancies. By providing a reassuring and supportive environment, women can achieve a positive pregnancy outcome with the correct tools to decrease anxiety and enhance attachment to the subsequent healthy child. PMID- 17273296 TI - Reducing the rate of cesarean birth. AB - This column examines recent research that illustrates the varying perspectives of cesarean birth and vaginal birth. PMID- 17273298 TI - Lamaze International's Must-Read List. PMID- 17273297 TI - Information for working mothers. AB - Women are entering, staying, or returning to the workforce following childbirth in increasing numbers. They report various amounts of success in the workplace after they become mothers. This column presents a review of five Web sites that provide useful resources to working Moms. PMID- 17273299 TI - What if ... ? AB - In this column, a childbirth educator wonders how to impress upon parents the importance of accepting their children for who they are, just as they are. PMID- 17273300 TI - The egyptian goddess of birth. PMID- 17273301 TI - Normal birth as the standard versus cesarean as a "deserved" choice. AB - In this column, childbirth educators are urged to provide pregnant women with informed choices, not just deserved choices, of giving birth. PMID- 17273302 TI - Promoting, protecting, and supporting normal birth. AB - This column discusses ways in which childbirth educators can promote, protect, and support normal birth to help make it the standard. PMID- 17273303 TI - Focus groups to reveal parents' needs for prenatal education. AB - Focus group interviews are a useful qualitative research technique to obtain data from small groups about their opinions, attitudes, and/or feelings on a given subject. This particular technique has been used in Western Quebec in order to reveal the opinions, needs, and feelings of health professionals and future parents concerning prenatal education. As part of the region's priorities for 2002, all future parents in this part of the province were to be offered prenatal, government-paid, community health education. Consequently, the Ministry of Health at the regional level sought a customized program for all community centers, based on identified regional needs and recent research. This program had to prove to be innovative, user-friendly, effective, and efficient. After reviewing the literature and conducting discussions with representatives from all regional health agencies throughout the province, the author of this article designed and conducted focus groups with perinatal health professionals from all community centers and hospitals of the Outaouais region. Later, focus groups were also conducted with parents. Following the analysis of the data and comparisons with existing resources, the author of this paper designed and proposed a specific program aimed at the empowerment of future parents. This paper reports the original problem and its context, the research methodology, and the proposed program (underlying philosophy, objectives, content, and educational techniques). PMID- 17273304 TI - Childbirth education outcomes: an integrative review of the literature. AB - The purpose of this literature review was to identify and describe recent empirical studies of childbirth education outcomes and to identify areas for further study. The search produced 63 studies; only 12 met the inclusion criteria. The literature demonstrated inconclusive evidence regarding the effectiveness of childbirth education. None of the studies used a theoretical framework that proposed multiple factors, as opposed to childbirth education alone, that impact the outcomes. Health-focused versus illness-focused outcomes were also addressed. PMID- 17273305 TI - Preparing expectant couples for new-parent experiences: a comparison of two models of antenatal education. AB - This paper describes a pilot antenatal education program intended to better prepare couples for the early weeks of lifestyle changes and parenting. Eight weeks after birth, data were collected by questionnaire from 19 couples who participated in a pilot program and from 14 couples who were enrolled in a routine hospital program. Women in the pilot program were significantly more satisfied with their experience of parenthood. Facilitated gender-specific discussion groups formed a key strategy in the pilot program. PMID- 17273306 TI - Smoking hygiene: an educational intervention to reduce respiratory symptoms in breastfeeding infants exposed to tobacco. AB - The American Academy of Pediatrics recently removed nicotine from the category of drugs contraindicated during breastfeeding. Little evidence demonstrates that infants exposed to nicotine through breastfeeding experience increased health risks beyond the airborne risks associated with passive smoking. The purpose of this longitudinal, five-week, quasi-experimental pilot study was to determine whether "smoking hygiene," an educational intervention, reduces the frequency of respiratory symptoms experienced by infants whose mothers both smoke and breastfeed. Twenty-nine mother-infant pairs entered the study with 28% dropping out. Of the 21 mother-infant pairs who completed the study, 66% of the nine infants in the control group experienced respiratory illness, compared to 42% of the 12 infants in the intervention group (x2 = .814; p > .05). Thus, the difference was statistically nonsignificant in this small sample, but the trend worsened the anticipated direction. The study demonstrates some of the difficulties of intervening with this group of mothers. PMID- 17273307 TI - Are LCCEs Exempt from Income Taxes? AB - Lamaze International Certified Childbirth Educators (LCCEs) may incorporate as tax-exempt organizations under the federal tax law if they meet all of the outlined requirements. They may then be considered exempt from income taxes for the purpose of any law that refers to tax-exempt organizations. PMID- 17273308 TI - Nutrition Column An Update on Water Needs during Pregnancy and Beyond. AB - Adequate water intake is essential to maintaining life. Pregnant and breastfeeding women should be encouraged to increase their intake of water and other fluids to meet their bodies' needs. Infants do not need additional water; breast milk or formula contributes adequate amounts of water to their diet. PMID- 17273309 TI - Misoprostol-is more research needed? AB - Misoprostol (Cytotec) is a synthetic prostaglandin E1 analogue that was designed for the prevention and treatment of peptic ulcer associated with the use of nonsteroidal anti-inflammatory drugs. In obstetrics, misoprostol has been administered for induction of first and second trimester abortion, for induction of labor in the third trimester, and to control postpartum hemorrhage. None of these uses has been approved by the Food and Drug Administration. Nevertheless, misoprostol is widely used in the United States and throughout the world. Advantages are cited as reduced rate of cesareans, shorter time from induction to birth and, particularly in developing countries, lower cost, oral, vaginal or rectal administration, and stability without refrigeration. Disadvantages are uterine hyperstimulation and, in rare instances, uterine rupture and death. Mothers should be informed of both the risks and the possible benefits of misoprostol. Further research with large samples is necessary to determine whether the risks outweigh any possible benefits. PMID- 17273310 TI - Web Sites that Address Postpartum Depression. AB - This column reviews four Web sites that address postpartum depression. PMID- 17273312 TI - The sixth sense. PMID- 17273311 TI - Scowlers, squeamers, and scoffers. AB - Prenatal educator humorously reflects on misjudging class participants' personalities. PMID- 17273313 TI - Old childbirth educators never die ... They just labor away. AB - Teaching childbirth education classes year after year can become monotonous or stale for some educators. Consequently, their students may also become bored. Rejuvinating one's professional self takes effort; however, the results are a renewed sense of purpose and a more exhilarating atmosphere in class. PMID- 17273314 TI - Dancing with the one who "brung" you into perinatal education. AB - The childbirth education movement began with creating a cultural shift to foster understanding that women should have choice in their birth. It has moved to the perinatal education movement with recognition that there are many teachable perinatal moments. PMID- 17273315 TI - Home birth: safely protecting and supporting normal birth. AB - In this column, the author examines the safety and advantages of home birth. She urges childbirth educators to promote normal birth by encouraging pregnant women to consider the option of home birth. PMID- 17273316 TI - Integrating marriage education into perinatal education. AB - Couples making the transition to parenthood experience challenges that can threaten the quality and stability of their relationships and the health of family members. Currently, the educational infrastructure to support the delivery of couple-relationship education during the transition to parenthood is limited. Because new-parent couples interact with the health care system at many points during this transition time, an opportunity exists for strengthening couple relationships within the system to improve the well-being of adults and children. In this article, we propose a productive collaboration between marriage/couple educators and health care systems to integrate couple-relationship education into the standard of perinatal care. PMID- 17273317 TI - Activist for change: an interview with suzanne arms. AB - Suzanne Arms's name is readily recognized by many in the field of perinatal education. For 30 years she has been a tireless advocate for childbearing women, a fighter for change in the traditional maternity care system, and a feminist with strong beliefs about the physical, emotional, and spiritual impact of birth. Arms's well-known books and frequent speaking engagements have allowed her to spread her message and her plea to humanize the childbirth experience. Talking with Arms is an energizing encounter. Her life path is a powerful and compelling story that is an inspiration to all who continue to work to make birth a positive event in the lives of women and their families. PMID- 17273319 TI - Preterm birth: a continuing challenge. AB - Although preterm birth has been a major focus of study for the past two decades by health care providers in several disciplines, it remains more prevalent in the United States than in many developed countries and continues to be a prime reason for infant death (mortality) and illness (morbidity). In the past 10 years, preterm rates have risen in the United States from 10.6% in 1990 to 11.6% in 2000. Low birthweight rates have increased from 7.0% in 1990 to 7.6% in 2000. This column reviews recent studies addressing preterm and low birthweight births, including changing demographics, the role of assisted reproductive technology, smoking, domestic violence, the experience of women, and treatment strategies. PMID- 17273318 TI - Postpartum depression, marital dysfunction, and infant outcome: a longitudinal study. AB - This longitudinal study explores the relationship of postpartum depression (PPD) and marital dysfunction on infant outcomes from birth to 2 1/2 years of age among middle-class, postpartum women. Participants were recruited during the prenatal period. Twelve mothers completed the study throughout a 2 1/2-year period. Questionnaires, semistructured interviews, and observations were used to collect data. Content analysis of the interviews (Morse & Field, 1995) was conducted and thematic patterns were identified. Clinical PPD and marital dysfunction (defined as little or no support or closeness, or verbal, emotional or physical abuse) characterized nearly one in three mothers. Four themes describing the women's postpartum progression were identified: stress, isolation, resentment, and eventual adjustment by creating a new normal. No major developmental delays or behavioral problems were found among the infants. Eight of the 12 mothers who were initially identified as breastfeeding nursed their infants for 6-18 months. Regardless of financial and educational advantages, mothers in the study experienced depression and marital dysfunction. These findings support other studies that confirm the lack of association of PPD with social class or marital status. Childbirth educators and other health care professionals are encouraged to continue providing expectant families with anticipatory education and community resources in order to increase awareness of mental health and marital risks during the postpartum transition. PMID- 17273320 TI - HIV and Pregnancy Web Sites. AB - This column reviews seven Web sites that address HIV and pregnancy. PMID- 17273321 TI - Potty training. AB - In this column, a childbirth educator takes a humorous look at bladder control. PMID- 17273322 TI - Trail mix. PMID- 17273323 TI - Post-ecstatic birth syndrome. AB - In this column, the author suggests the use of positive terminology as a way to influence the dominant viewpoint of childbirth towards the midwifery model of care. PMID- 17273324 TI - Listening to Mothers-The First National U.S. Survey of Women's Childbearing Experiences. AB - In this column, the author outlines some of the results of the Listening to Mothers Survey, conducted by the Maternity Center Association, and the implications of the results on childbirth education. PMID- 17273325 TI - Previous traumatic birth: an impetus for requested cesarean birth. AB - This paper addresses the meaningfulness of the childbearing experience and how a traumatic occurrence can affect women for years into the future. Every woman deserves to have a fulfilling childbearing experience, even if it may be different from the one she imagined. This paper examines the phenomenon of previous traumatic birth and its potential effects on choices during subsequent pregnancies. Discussion includes how childbirth educators can assist women in healing from past birth traumas and preventing them from recurring. PMID- 17273326 TI - Aquatic-Aerobic Exercise as a Means of Stress Reduction during Pregnancy. AB - The goals of this research were to explore the current literature regarding associations between psychological stress and adverse fetal outcome, associations between aerobic exercise and psychological stress reduction, and associations between aerobic exercise and fetal outcome. The published studies that were located provide evidence of the following: 1) Stress reactivity increases physiologically during pregnancy, 2) pregnant women may experience additional stressors that are usually not experienced in a nonpregnant state, 3) psychological stress in pregnancy is associated with adverse fetal outcome, 4) exercise can be a method of stress reduction, 5) exercise in pregnancy is not associated with adverse fetal outcome, and 6) exercise in pregnancy may provide benefit to the fetus. Data were analyzed from an original study and associations were reported between psychological stress-management activities and participation in aquatic aerobic exercise classes. No reports were available investigating an exercise-induced reduction in psychological stress with fetal outcome. PMID- 17273327 TI - Woman-centered maternity nursing education and practice. AB - The purpose of this Heideggerian phenomenological study was to uncover the meanings of the clinical experiences of registered nurses working in maternity settings after they studied maternity nursing from a woman-centered, feminist perspective in a generic baccalaureate nursing program. Purposeful sampling was conducted to locate and recruit nurses who had graduated from this nursing program between the December 1996 and December 1998 semesters and were currently working in a maternal-newborn clinical setting. Each participant had taken the required woman-centered, maternity-nursing course during her/his undergraduate education. Data collection included an individual, open-ended interview that focused on the nurses' descriptions of their everyday practices as maternity nurses. Nineteen maternal-newborn nurses between the ages of 23 and 43 years who had been in practice from six months to three years were interviewed. The constitutive patterns identified from the interviews were: "Otherness," "Being and Becoming Woman-Centered," and "Tensions in Practicing Woman-Centered Care." Findings revealed that the nurses had a raised awareness of oppressive maternity care practices and applied ideology of woman-centeredness as a framework for providing more humanistic care. Creating woman-centered maternity care meant negotiating tensions and barriers in medically focused maternity settings and looking for opportunities for advocacy and woman-empowerment. The barriers the nurses faced in implementing woman-centered care exposed limitations to childbearing choices and nursing practices that remain problematic in maternity care. PMID- 17273329 TI - Nutrition and HIV-Positive Pregnancy. AB - When an HIV-positive woman becomes pregnant, additional nutritional considerations are warranted. Compared to routine prenatal nutritional assessment and intervention, pregnant HIV-positive women have increased needs to promote a healthy outcome. This column contains information on HIV and pregnancy, nutrition and infection, and nutrition for HIV-positive pregnancy. This content can be integrated into childbirth education settings to improve care to women who are HIV-positive. PMID- 17273330 TI - Web Sites that Address Gestational Diabetes and Perinatal Obesity. AB - Obesity contributes to multiple health problems during pregnancy and predisposes a woman to develop gestational diabetes. This column reviews the currently best Web sites that address gestational diabetes and obesity during the perinatal period. PMID- 17273328 TI - A web-based breastfeeding education program. AB - Two Web-based breastfeeding programs were developed to provide new parents with necessary information on proper breastfeeding techniques. One version was plain text and the other version combined text with graphics. The computer was viewed as a valuable learning tool. The breastfeeding program that contained graphics was preferred over the text-only program. Educators are encouraged to use Web based graphic programs to provide breastfeeding education to new parents. PMID- 17273331 TI - There's No Credential Like Show Credential. AB - In this column, the author takes a humorous look at conference attendees' name tags. PMID- 17273332 TI - Your feet. PMID- 17273333 TI - Decision latitude in childbirth. AB - Decision latitude in the workplace and a mother's perception of control in the labor of childbirth are highly related concepts. Both concepts have been shown to be important to the health and development of laboring humans. PMID- 17273334 TI - "Reality" birth: marketing fear to childbearing women. AB - In this column, the authors examine the effect of "reality" television shows on expectant parents' fears of childbirth. PMID- 17273335 TI - Childbirth experience in women at high risk: is it improved by use of a birth plan? AB - Women at obstetric high risk more often experience negative feelings related to childbirth than women with normal outcomes. For these high-risk women, an individual birth plan does not appear to improve the overall experience of childbirth; rather, it seems to intensify the negative feelings in several aspects. The increased vulnerability in women at high risk warrants special attention to the possibility that types of care routinely offered to all women may negatively influence the experiences of high-risk women. PMID- 17273336 TI - Exploring Women's Preferences for Labor Epidural Analgesia. AB - The purpose of this study was to explore demographic factors related to women's prenatal preferences for using an epidural during labor. Women recruited from prenatal classes provided data for this descriptive correlational study. Women with the most education, income, and parity indicated greatest preference for epidural analgesia. Thus, these women may be comfortable with the technology and most likely to be willing to pay for epidurals and to select care providers who provide epidural anesthesia. In this sample, prenatal preference for an epidural was not predictive of actual use, although it has been shown to be predictive in previous research. PMID- 17273337 TI - Improving nutrition in pregnant adolescents: recommendations for clinical practitioners. AB - Pregnancy represents an ideal time for health promotion activities. Many women, including adolescents, are interested and willing to change health behaviors to improve the chance that they will deliver a healthy infant. This paper focuses on improving nutrition in pregnant adolescents. Seven recommendations are presented to help achieve this goal: 1) Focus on foods, not nutrients; 2) individualize and work within the pregnant adolescent's current eating habits; 3) consider the context of family and peer groups; 4) reward efforts; 5) make it easy; 6) focus on weight gain patterns for optimal birth outcomes; and 7) refer to a dietician, as needed. Use of these recommendations comprehensively addresses adolescent developmental needs to improve nutrition during pregnancy. These recommendations are not meant to be all-inclusive; rather, they are meant to serve as a guide for clinical management of nutrition for pregnant adolescents. PMID- 17273338 TI - Nurses' attitudes and knowledge of their roles in newborn abandonment. AB - The practice of abandoning newborns shortly after birth has always existed. Occurring in primitive and contemporary societies, the motivations for newborn abandonment are varied and dependent upon the social norms of a specific geographic region at a given point in time. Because the desire to abandon an infant has had no support system in American society, such unwanted infants have been abandoned in a manner leading to their deaths. In response, many states have passed safe-haven legislation to save the lives of unwanted newborns. The laws typically specify a mother's ability to "abandon" her child to a medical service provider. However, judgmental attitudes and a lack of accurate information may impede a health care provider's ability to carry out a safe-haven law. The study described here examines a sample of nurses in a state with a safe-haven law. The study revealed no significant correlation between a nurse's knowledge, attitude, and self-perception of preparedness to manage a newborn abandonment event. owever, the outcomes highlight the negative attitudes and lack of knowledge many nurses possess regarding newborn abandonment and the women who commit this act. Educational programs for all health care providers and the community are essential to the efficacy of the legislation that currently exists. Continued multidisciplinary strategizing and general awareness are needed to serve as catalysts to build supports for unwanted newborns and their safe assimilation into the community. PMID- 17273339 TI - Abandoned-baby laws. AB - In this column, the author examines the current status of abandoned-baby laws in the United States and how it can impact the work of childbirth educators. PMID- 17273340 TI - Current studies on two separate topics: breastfeeding postpartum length of hospital stay. AB - IN THIS COLUMN, THE AUTHOR EXAMINES RECENT RESEARCH ON TWO SEPARATE TOPICS: 1) breastfeeding; 2) postpartum length of hospital stay. Recent studies suggest long term effects of breastfeeding that benefit both mother and infant. Benefits include a reduced risk of breast cancer in breastfeeding mothers and a reduced level of total and LDH cholesterol in adults who were breastfed as infants. Infants of mothers with maternal asthma had lower rates of asthma if the mother breastfed. In a study of women in the United States who planned to breastfeed, those mothers who breastfed exclusively and planned to breastfeed more than three months were more likely to achieve their goals than mothers who planned to combine breast and human-milk substitute feeds and to breastfeed less than three months.In a Canadian study, shortened postpartum stays led to increased re admission to hospital for mothers with cesarean births. In contrast, in a Massachusetts study, shortened postpartum stays did not lead to an increase in infant visits for urgent care. However, the Massachusetts study did not reflect a decrease in maternity-related costs associated with shortened length of postpartum stay. PMID- 17273341 TI - Web Sites that Address Perinatal Physical Activity. AB - In this column, the author provides examples of Web sites that address exercise and physical activity during pregnancy and the postpartum period. PMID- 17273342 TI - My memorial garden. AB - In this article, a doula describes one way in which she can honor infants who died prematurely. PMID- 17273343 TI - Recommended reading and viewing. PMID- 17273345 TI - Glamour shot. PMID- 17273344 TI - Just the Facts, Ma'am. AB - In this column, the author humorously relates how a childbirth educator transporting medical antiques caused a stir in airport security. PMID- 17273346 TI - Childbirth education in a world of challenges. AB - In this column, the author considers the impact of widespread crises and global tensions on pregnancy and early parenting. Childbirth educators can help alleviate the impact of societal stress on expectant families. PMID- 17273347 TI - A reclamation of childbirth. AB - In the first of a two-part article, the author recounts the childbirth experiences of her mother and grandmother, as well as her own, providing a view of three distinct eras and revealing profound changes in how American culture manages and understands birth. PMID- 17273348 TI - The Impact of SARS on Childbirth Education. AB - The SARS (Severe Acute Respiratory Syndrome) crisis in Toronto in the spring of 2003 had major consequences for prenatal learners. Classes in hospitals were cancelled; many couples were left without any prenatal education. This paper outlines the decision-making process of one programme that was determined to keep classes open. The impact of SARS on hospital procedures is also described. Childbirth educators are encouraged to prepare for future public health emergencies. Strategies to prepare for conducting childbirth education classes during times of crisis are outlined. PMID- 17273349 TI - Breastfeeding Attitudes of WIC Staff: A Descriptive Study. AB - A sample of staff members from the Special Supplemental Nutrition Program for Women, Infants and Children (WIC program) were interviewed about breastfeeding and their perceptions of WIC recipients' views on breastfeeding. WIC staff members universally supported breastfeeding and expressed desires for more linkages between WIC agencies and perinatal education specialists in childbirth education classes, as well as with mothers during their postpartum hospital stay. The WIC staff members in this study reported on a variety of beliefs about breastfeeding held by their WIC clients, including cultural beliefs, the importance of family support, and experiences of pain during breastfeeding. PMID- 17273350 TI - Perinatal experiences: the association of stress, childbearing, breastfeeding, and early mothering. AB - The support of women and their families through childbirth, breastfeeding, and early parenting experiences are often treated as separate areas of maternity care. In fact, growing evidence, as cited in this article, links their intertwined impact on the health of mothers, infants, and their families. PMID- 17273351 TI - Soy protein. AB - Soy protein comes from soybeans and offers multiple health benefits, some of which are just beginning to be discovered. This column reviews the health benefits of soy products with a special focus on women and children's health. To date, little has been written or researched that is directly related to perinatal health. Thus, the column has a more broad focus so that childbirth educators have a general resource to gain knowledge related to the use of soy-based foods. PMID- 17273352 TI - Recent research questions the values of routine intervention. AB - Under appropriate circumstances, intervention in labor and birth can be valuable, even lifesaving. But interventions can also become routine procedures. This paper reviews three recent studies in which the focus of research is common interventions: electronic fetal monitoring and epidural anesthesia. A fourth study reviewed here examines the effect of previous vaginal birth and fetal weight on the success of vaginal birth after cesarean. PMID- 17273353 TI - Web Resources that Address Psychiatric Disorders in Pregnancy. AB - Psychiatric disorders occur at every life stage, including pregnancy. This resource column highlights several Web resources that may be useful to childbirth educators and other health care providers who may care for pregnant woman experiencing one of these conditions. PMID- 17273355 TI - Show time. PMID- 17273356 TI - Overcoming isolation of the new mother. AB - Isolation is a frequently mentioned and long-remembered issue for new mothers in a North American culture. Perinatal educators can play a role in helping new parents build support systems that are designed to diminish the experience of postpartum and new-parent isolation. PMID- 17273354 TI - The mother of all inventions. AB - Crusty childbirth educator humorously reflects upon the conveniences of modern day parenting. PMID- 17273357 TI - Uncovering your own birth history. AB - In the second of a two-part article, the author encourages women to learn about their mothers' and grandmothers' birth experiences as a way to celebrate and record their family's legacy of childbirth. PMID- 17273358 TI - Childbirth education and doula care during times of stress, trauma, and grieving. AB - A collaborative, interspecialty volunteer program extending for nine months after September 11, 2001, provided free support and service to pregnant women widowed by the attacks on the World Trade Center. Participating providers studied the physiological and psychological effects of stress. Group sharing, discussions about the effects of emotions on labor progress, and other techniques were incorporated into sessions. The program's success suggests that childbirth educators should prepare all pregnant women to cope with stress. Subsequent national and international events have reinforced the importance of such training. The childbirth educator can also help by maintaining a referral list of local trauma counselors and other resources. PMID- 17273359 TI - Public display of affection in couples attending childbirth education classes: implications for practice in Thailand. AB - The purpose of this article is to describe couples' touch behaviors and positions during their interactions in childbirth education class exercises in the United States-practices that might be construed differently among couples in Thailand. Using observations collected at childbirth education classes conducted in the United States during the fall of 2002, the author found four positions that would be considered culturally sensitive with her Thai experiences. Perhaps with some modifications in the technique, mothers and their partners in Thailand will more readily accept childbirth education classes. PMID- 17273360 TI - Childbirth Education for the HIV-Positive Woman. AB - Pregnant HIV-positive women have unique education needs during the perinatal period. HIV-positive women need information regarding the differences in recommended care they can expect to experience both for themselves and their newborn. Differences in recommended care are related to minimizing transmission of the HIV virus. This article discusses the unique educational content needs of HIV-positive pregnant women. Providing women with appropriate information about what their labor and delivery experiences will entail can help them make decisions and promote a positive birth experience. PMID- 17273362 TI - Childbearing Women's Fears: At the Heart of "Choice". AB - In this column, the author examines how the promotion of medical birth feeds into women's natural concerns about pregnancy and birth and, consequently, negatively influences their childbirth choices. PMID- 17273361 TI - Maternal-fetal attachment in african-american and Hispanic-american women. AB - This pilot study used Cranley's Maternal-Fetal Attachment Scale (MFAS) to explore the feasibility of comparing maternal-fetal attachment behaviors of African American and Hispanic-American gravidas. Data analysis revealed no significant differences between the two groups' MFAS total scale score means; however, the Hispanic-American gravidas displayed significantly higher scores in two of the subscales. While study limitations were apparent, the results lend support to health care professionals' responsibilities to be cognizant of potential similarities and differences in the cultural care needs of pregnant women. PMID- 17273363 TI - When Parents Ask ... about Preterm Birth, Breastfeeding Success, Breast Cancer, or Waterbirth. AB - IN THIS COLUMN, THE AUTHOR REVIEWS RESEARCH ON FOUR SEPARATE TOPICS: the prevention of preterm birth, the effect of epidurals on breastfeeding success, the possible protective effect of lactation on breast cancer, and laboring in water. In two separate studies-a multisite study in the United States and a second study from Brazil-natural progesterone was shown to significantly reduce the incidence of preterm birth in women at high risk. A third study conducted in the United Kingdom examined the effect of clindamycin on preventing infection that can lead to preterm birth. A group of studies related to lactation found that early breastfeeding was more successful in women who did not have epidural anesthesia. In a Korean study, the lifetime duration of breastfeeding was associated with a significant reduction in breast cancer. Concerning waterbirth, Swiss researchers found that, when a woman labored in water, she regulated both water temperature and bathing duration to ensure that her body temperature and that of the fetus remained within a normal physiological range. PMID- 17273364 TI - Examining insurance needs for childbirth educators. AB - In this column, the author presents three questions that childbirth educators may ask themselves in order to decide whether or not they should invest in insurance coverage. PMID- 17273365 TI - Web site resources for waterbirth. AB - In this column, the author reviews Web sites that provide information and resources on waterbirth. PMID- 17273367 TI - Kangaroo care. PMID- 17273366 TI - Excuses, excuses, excuses. AB - In this humor column, a perinatal educator learns that explanations are not always necessary when one is a grownup. PMID- 17273368 TI - Will birth attendants need to promote high-tech intervention to afford malpractice insurance? AB - In this column, the author examines the trends of the midwifery model of care versus nonmedically indicated cesarean births and their effect on malpractice insurance rates. Childbirth educators are encouraged to support a health-care system that promotes normal birth. PMID- 17273369 TI - Integrating Lamaze International's Vision and Mission Statements in Childbirth Education Classes. AB - In this column, the author discusses ways in which childbirth educators can introduce and employ Lamaze International's vision and mission statements in their classes. PMID- 17273370 TI - Modified breastfeeding attrition prediction tool: prenatal and postpartum tests. AB - In earlier studies, the Breastfeeding Attrition Prediction Tool (BAPT) demonstrated predictive validity in the postpartum period. The purpose of this study was to compare the effectiveness of a modified version of the BAPT when given in the last trimester (BAPT1) and following delivery (BAPT2) in predicting breastfeeding attrition among 117 women who planned to breastfeed for at least 8 weeks. Subjects completed the BAPT during a prenatal breastfeeding class and again at delivery, and they received a phone call at 8 weeks to determine breastfeeding status. In this study, neither of the two administrations of the BAPT was predictive of breastfeeding status at 8 weeks. Findings here may differ because subjects in the current study were all committed enough to attend breastfeeding class and, thus, varied less on commitment than women in earlier studies. Significant associations were found with level of education and having a close relative who breastfed. To assist the perinatal educator in identifying women most at risk for early cessation of breastfeeding, the use of three questions regarding level of education, family support, and breastfeeding preparation is suggested. PMID- 17273371 TI - Supine and prone infant positioning: a winning combination. AB - Since 1992, the optimal sleeping position for infants in the United States has been supine. This position has been shown to greatly reduce the rate of Sudden Infant Death Syndrome (Skadberg, Morild, & Markestad, 1998). However, the supine position may lead to other unintended consequences or complications. Through a review of literature, this article explores some of the complications associated with the "Back to Sleep" campaign in the U.S. and discusses educational strategies for perinatal educators. PMID- 17273372 TI - Report from the Country of Georgia: Protecting and Promoting Breastfeeding through Regulation of Artificial-Feeding Marketing Practices. AB - This paper highlights the southwest Asian country of Georgia's experience in creating efforts to protect and promote breastfeeding and to implement the International Code of Marketing of Breast-milk Substitutes. Since 1994, the country of Georgia (of the former Soviet Union) has successfully implemented the Baby-Friendly Hospital Initiative. In 1997-1998, Georgia conducted a study throughout the country's various regions to evaluate compliance with the International Code of Marketing of Breast-milk Substitutes. The research demonstrated numerous violations of the code by various companies and confirmed the necessity of ongoing activities to promote implementation of the code. Due to the great effort of Georgia's Ministry of Health and the International Baby-Food Action Network [IBFAN] Georgian group called "Claritas," the law titled "On Protection and Promotion of Breastfeeding and Regulation of Artificial Feeding" was adopted in 1999 by the country's parliament. As a result, Georgia has witnessed a sharp increase in breastfeeding percentages, the designation of baby friendly status at 14 maternity houses, and a decrease in the advertisement of artificial-feeding products. PMID- 17273373 TI - Pain reduction and treatment of sore nipples in nursing mothers. AB - Health-promotion goals include increasing the duration of breastfeeding because of its irrefutable advantages to the mother and baby, society, and the environment. However, many mothers experience painful, sore nipples during breastfeeding and stop nursing before they intended (Livingstone & Stringer, 1999). The experimental trial described in this paper randomized 94 breastfeeding women with sore nipples into three treatment groups. Midwives practicing in hospitals in Latvia assessed the participants' breastfeeding practices, then gave the mothers individualized education and corrective interventions using a guided documentation form, the Lactation Assessment Tool (LATtrade mark). In addition, two groups were instructed to use commercial products on their breasts and nipples: breast shells and lanolin cream for one group, and glycerin gel therapy for the other. Nipple pain during breastfeeding was rated by the mothers on a 5 point verbal descriptor scale at each visit, and pain at the start of treatment was compared to pain at the last visit. Analysis of variance (using Fisher's Exact Test) determined that no significant differences existed between the groups: F(2, 86) = 1.34, p > .05. Almost all of the mothers experienced nipple healing, as assessed by the midwife. Mothers in the glycerin gel group were more satisfied with their treatment method, but this finding was not statistically significant. The results of this study indicate that effective care and perinatal education for nursing mothers with sore nipples should include assessment of breastfeeding positioning and latch-on, as well as education and corrective interventions using a guidance tool, whether or not commercial preparations are used. PMID- 17273374 TI - Identity security awareness. AB - Identity theft is an increasing concern when organizations, businesses, and even childbirth educators ask for a client's Social Security number for identification purposes. In this column, the author suggests ways to protect one's identity and, more importantly, decrease the opportunities for identity theft. PMID- 17273375 TI - Current studies on two populations: childbearing teens and women with cesarean births. AB - Young women in their teen years and women who have had previous cesarean births are two special groups taught by Lamaze Certified Childbirth Educators. This review includes research related to both groups. Information collected from these studies can help childbirth educators assess their programs and plan appropriate classes that address the particular needs of each group. PMID- 17273376 TI - Styles of parenting. AB - IN THIS BRIEF OVERVIEW, THE AUTHOR CONTRASTS TWO CURRENT PARENTING STYLES: Attachment Parenting and Babywise Parenting. PMID- 17273377 TI - Web Sites that Address Prematurity. AB - Families of preterm infants need a tremendous amount of support. This resource column highlights several Web sites that may be useful to health care providers and childbirth educators, as well as to parents of premature infants and their families. PMID- 17273379 TI - Mug shot. PMID- 17273378 TI - Finding humor in the mundane. AB - In this column, the author encourages everyone to find humor in the daily routine...and to use more lotion. PMID- 17273380 TI - Sharing the value of normal birth. AB - In this column, the author introduces a special issue of the Journal of Perinatal Education, in which a position paper and six care practice papers, published by Lamaze International and reprinted here with permission, are presented along with accompanying commentary. Together, these papers present evidence in support of the six care practices that promote, protect, and support normal birth. PMID- 17273381 TI - Promoting, protecting, and supporting normal birth. AB - In this professional paper, published by Lamaze International and reprinted here with permission, Lamaze International identifies six care practices-adapted from the work of the World Health Organization-that promote, protect, and support normal birth. The six care practices are: labor begins on its own; freedom of movement throughout labor; continuous labor support; no routine interventions; non-supine (e.g., upright or side-lying) positions for birth; and no separation of mother and baby with unlimited opportunity for breastfeeding. Evidence to support each care practice is presented. Health-care providers and places of birth are encouraged to adopt these care practices as standards of care. Additionally, women are encouraged to choose health-care providers and places of birth whose care practices promote, protect, and support normal birth. PMID- 17273382 TI - #1: labor begins on its own. AB - In this position paper-one of six care practice papers published by Lamaze International and reprinted here with permission-the benefit of allowing labor to begin on its own is discussed and presented as an evidence-based practice that helps promote, protect, and support normal birth. The paper is written for childbearing women and their families. The accompanying commentary-written by a leading home-birth midwife and prominent national and international speaker on maternity care-describes further evidence of the disadvantages of inducing labor. The indications for and risks of induction are also explored. Lamaze International recommends that, unless there is a medical indication for induction, labor should be allowed to begin on its own. PMID- 17273383 TI - #2: Freedom of Movement throughout Labor. AB - In this position paper-one of six care practice papers published by Lamaze International and reprinted here with permission-the benefit of allowing freedom of movement throughout labor is discussed and presented as an evidence-based practice that helps promote, protect, and support normal birth. The paper is written for childbearing women and their families. The accompanying commentary written by a well-known author of numerous articles and books on childbirth compares the activities of women in two birthing environments: the conventional medicalized setting and the unconventional naturalistic setting. Reasons why women may not move in labor are presented. Lamaze International encourages women to use movement in labor in order to make labor more comfortable and more efficient. PMID- 17273384 TI - #3: continuous labor support. AB - In this position paper-one of six care practice papers published by Lamaze International and reprinted here with permission-the benefit of continuous labor support is discussed and presented as an evidence-based practice that helps promote, protect, and support normal birth. The paper is written for childbearing women and their families. Women with continuous support are less likely to have a cesarean, an instrument delivery, and regional anesthesia. They are also less likely to report dissatisfaction with or negatively rate their childbirth experience. The value of the doula for both the laboring woman and her labor partner is discussed. The accompanying commentary-written by a leading proponent of maternity care practices-supports evidence that promotes continuous labor support. Lamaze International encourages women to plan for a supportive birth environment that includes continuous support. PMID- 17273385 TI - #4: no routine interventions. AB - In this position paper-one of six care practice papers published by Lamaze International and reprinted here with permission-the benefit of no routine interventions during birth is discussed and presented as an evidence-based practice that helps promote, protect, and support normal birth. The paper is written for childbearing women and their families. It presents evidence related to restrictions on eating and drinking, use of intravenous fluids, continuous electronic fetal monitoring, artificial rupture of the membranes, augmentation of labor, and epidural analgesia. The accompanying commentary-written by an award winning medical writer-supports and expands on the benefits of no routine interventions during birth. Lamaze International recommends that laboring women avoid restrictions on eating and drinking. The organization also recommends avoidance of IVs, continuous electronic fetal monitoring, epidurals, and efforts to speed up labor, unless a clear indication for their use is evident. PMID- 17273386 TI - #5: Non-Supine (e.g., Upright or Side-Lying) Positions for Birth. AB - In this position paper-one of six care practice papers published by Lamaze International and reprinted here with permission-the benefit of non-supine positions for birth is discussed and presented as an evidence-based practice that helps promote, protect, and support normal birth. The paper is written for childbearing women and their families. Upright and gravity-neutral positions facilitate rotation and descent of the baby and result in reduced duration of second stage, a reduction in episiotomies, and fewer abnormal fetal heart rate patterns. The accompanying commentary-written by a leading proponent of maternity care-supports these benefits. Lamaze International recommends that laboring women not push until they feel an urge to do so, and that they choose positions for birth that are most comfortable for them. PMID- 17273387 TI - #6: no separation of mother and baby with unlimited opportunity for breastfeeding. AB - In this position paper-one of six care practice papers published by Lamaze International and reprinted here with permission-the value of keeping mothers and their babies together from the moment of birth is discussed and presented as an evidenced-based practice that helps promote, protect, and support normal birth. The paper is written for childbearing women and their families. Babies held skin to-skin with their mothers cry less often, breathe easier, and stay warmer than babies who are separated from their mothers. They also instinctively attach to the breast and begin breastfeeding, usually within one hour of birth. The advantages of rooming-in for mother and baby are also discussed. The accompanying commentary-written by two leading professionals in the field of maternity care and pediatrics-provides further evidence to support the practice of keeping mothers and their babies together after birth. Lamaze International encourages women to give birth in settings that do not separate mothers and babies after birth. PMID- 17273388 TI - Childbirth educators, doulas, nurses, and women respond to the six care practices for normal birth. AB - This collection of commentaries by childbirth educators, doulas, a labor and delivery nurse, and a woman preparing for the birth of her second baby provide an overall response to all six of Lamaze International's care practice papers that promote normal birth: Labor Begins on Its Own; Freedom of Movement throughout Labor; Continuous Labor Support; No Routine Interventions; Non-Supine (e.g., Upright or Side-Lying) Positions for Birth; and No Separation of Mother and Baby with Unlimited Opportunity for Breastfeeding. Strategies for using the position papers to facilitate learning in childbirth classes and for helping expectant parents access and understand research are presented. The commentaries describe the value of the position papers as a catalyst for professional growth, a foundation for creating change, a way to encourage reflection among professionals and women planning for the births of their babies, and an inspiration for everyone who advocates normal birth. PMID- 17273389 TI - Teaching normal birth interactively. AB - IN THIS COLUMN, THE AUTHOR PROVIDES EXAMPLES OF TEACHING STRATEGIES THAT CHILDBIRTH EDUCATORS MAY UTILIZE TO ILLUSTRATE EACH OF THE SIX CARE PRACTICES SUPPORTED BY LAMAZE INTERNATIONAL TO PROMOTE NORMAL BIRTH: labor begins on its own, freedom of movement throughout labor, continuous labor support, no routine interventions, non-supine (e.g., upright or side-lying) positions for birth, and no separation of mother and baby with unlimited opportunity for breastfeeding. PMID- 17273390 TI - You're So Vain in Labor. AB - In this column, a childbirth educator questions whether a place exists for vanity during labor. PMID- 17273391 TI - The rocker. PMID- 17273392 TI - The need for birth stories on perinatal pain. AB - Perinatal pain can be experienced by both mothers and infants. In this column, the author encourages readers to view an article by Gayle Page featured in this issue of the journal. Page's article shows the importance of protecting infants from unnecessary pain. The column author also points out that birth stories show the benefit of supporting women as they meet the challenges of a normal birth. PMID- 17273393 TI - Do not disturb: the importance of privacy in labor. AB - In nature, when a laboring animal feels threatened or disturbed, the stress hormone catecholamine shuts down labor. Similarly, when a laboring woman does not feel safe or protected or when the progress of her normal labor is altered, catecholamine levels rise and labor slows down or stops. This column discusses the importance of providing labor support that respects the woman's privacy, protects her from unnecessary interventions, insures her safety, and allows her to trust her inherent ability to give birth normally. PMID- 17273394 TI - Ethics of product endorsement: taking a look at freebies. AB - Childbirth educators are potentially a large vehicle for marketing promotions to young and purchasing parents. Many free materials-educational matter and product samples-are available for the educator's own use and for distribution to the parents who attend class for evidence-based information. In this column, the author encourages childbirth educators to use good judgment in selecting materials that will protect normal birth, encourage positive parenting, and promote breastfeeding. Educators must consider the effect a brand name will have on the purchasing power of parents and whether or not the materials or samples will undermine breastfeeding efforts. PMID- 17273395 TI - Are there long-term consequences of pain in newborn or very young infants? AB - Physiologic studies indicate that very early pain or stress experiences have more than immediate consequences for infants. Assessment and care of pain are complex subjects made even more complex and challenging when the individual experiencing pain is a very young infant. This review provides evidence that significant and long-lasting physiological consequences may follow painful insults in the very young, including changes in the central nervous system and changes in responsiveness of the neuroendocrine and immune systems to stress at maturity. PMID- 17273397 TI - Birth and a vision: lamaze childbirth education in kenya, East Africa. AB - Lamaze Certified Childbirth Education was an unknown entity in Kenya, East Africa, just a few years ago. Today, programs are firmly established in two leading private hospitals in Nairobi and gaining credibility in the region's medical community. Prepared childbirth is finding its place in the lives of the rapidly urbanizing African society. Implementation of Lamaze techniques in antenatal programs serving women outside the private sector is taking place as Kenyan midwives work toward their certification as Lamaze Certified Childbirth Educators. PMID- 17273396 TI - New fathers' postbirth views of antenatal classes: satisfaction, benefits, and knowledge of family services. AB - New fathers (men whose partners had recently given birth) were asked to indicate to what degree antenatal classes had prepared them for childbirth, for their role as support persons, and for lifestyle and relationship changes after the birth. These postbirth findings were compared with a previous exit survey of male attendants at antenatal classes in which fathers-to-be predicted that the antenatal classes had prepared them well on all fronts. The new fathers in this study, however, reported that the antenatal classes had prepared them for childbirth but not for lifestyle and relationship changes after the birth. Additionally, couples who attended antenatal classes were asked to what extent they were familiar with family-related services in the region and how often they had used these services since the birth of their baby. Fathers were less familiar than mothers with the family-related services. PMID- 17273398 TI - Mothers' experiences of facilitated peer support groups and individual child health nursing support: a comparative evaluation. AB - The "Early Bird Program" is a support group facilitated by child and family health nurses and offered to families of infants aged 0-8 weeks in South East Sydney, Australia. This paper describes the experiences of 20 women who participated in the Early Bird groups and 20 women who chose to use individual consultations with the child and family health nurse. The qualitative evaluation used focus groups and interviews with the 40 women, and data were analysed using content analysis. Key findings show the Early Bird Program mothers received support and knowledge from both the nurses and each other, while the women who utilised the individual consultations with the nurses sought out and received specific services and information that focused on the baby. The group approach appears to promote group relationships and to empower mothers as a group by de emphasising the power and expertise of the professional. PMID- 17273400 TI - Promoting and implementing evidence-based, best practices in childbirth education. AB - Childbirth educators have a duty to promote and implement best practices. Best practices are individualized and evidence-based, using quality research to optimize outcomes. This requires addressing change. The childbirth educator must model evidence-based practices by systematically engaging in activities to improve his or her own changing curriculum. The childbirth educator is also a professional in a core position to play an active role as a change agent in the system through evaluation and dissemination of information to parents, fellow childbirth educators, and other professionals on the health-care team. This information provides the basis for important health-care decisions for self and others. PMID- 17273401 TI - Perceptions of nurses and mothers in four studies of the peripartum period. AB - How individuals perceive themselves and how they are perceived by others are an important part of the relationships between childbirth educators, nurses, other health-care providers, and the families they serve. In this paper, four studies are reviewed. One study focused on labor nurses' perception of their roles. Three other studies, each using a different research strategy, examined mothers' perceptions of their experiences during the peripartum period. PMID- 17273399 TI - Assessing infant breastfeeding beliefs among low-income mexican americans. AB - Focus groups were conducted with low-income, pregnant women and new mothers receiving services from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC program) along with their male partners and their mothers. All participants were Hispanics of Mexican American origin. The topics for the focus-group discussions were breastfeeding beliefs and perceptions. All participants were aware of the benefits of breastfeeding. Participants identified time, embarrassment, and pain as barriers to breastfeeding; discussed decision making efforts regarding breastfeeding; identified cultural beliefs related to breastfeeding; and discussed the lack of care-provider support for breastfeeding. PMID- 17273402 TI - New Resource from the CDC to Prevent Obesity: Perinatal Implications. AB - Research has identified pregnancy as a trigger to obesity among women; therefore, childbirth educators are encouraged to include the topic of weight gain in their classes. The Centers for Disease Control and Prevention recently published a guide on obesity that may serve as an excellent resource for both educators and their clients. PMID- 17273403 TI - You look marvelous. AB - In this column, the author is reminded that maternity fashion and her own sense of clothing styles often leave much to be desired. PMID- 17273404 TI - Pondering. PMID- 17273405 TI - The power of perceptions of childbearing. AB - Documenting women's perceptions of childbearing experiences can help other pregnant women with their own birth decisions. PMID- 17273406 TI - Transition of maternal competency of married and single mothers in early parenthood. AB - Women who perceive maternal competency in early parenthood feel comfortable with infant care. A convenience sample of 58 married, first-time mothers and 22 single, first-time mothers was surveyed at six to eight weeks after childbirth to determine the differences in maternal competence perception between married and single mothers. Findings in this pilot study reveal that single mothers significantly reported less comfort in the maternal role as compared to married mothers. Implications for practice, research, and education are discussed. PMID- 17273407 TI - Characteristics of a positive experience for women who have unmedicated childbirth. AB - This qualitative descriptive study determined characteristics that women deem positive in their unmedicated childbirth experience. Seventeen women were interviewed and themes were identified. All of the women reported satisfying births, adding accompanying feelings of empowerment and well-being. An overriding theme in each woman's birth story that made the birth experience positive was the ability to control her body during labor and the ability to influence the environment in which she labored and gave birth. Being able to move and change positions freely were both key factors in determining a positive birth experience. Additionally, the women expressed comfort from the presence of a spouse or trusted individual. They found the help of an experienced woman or doula important. Many were willing to change care providers to gain support for their desire for an unmedicated birth. PMID- 17273408 TI - A comparison of blood pressure in term, low birth-weight infants of smoking and nonsmoking mothers. AB - Infants exposed to the components of cigarette smoke in utero are at an increased risk for perinatal death, low birth weight, sudden infant death syndrome, and premature delivery. The purpose of this pilot study was to compare blood pressure values in term low-birth weight infants ( .70) were found between certain neuropsychological measures. CONCLUSIONS: We found moderate test-retest reliability on the cognitive tests that assessed attention, concentration, and visual processing and the Balance Error Scoring System. Our results demonstrated only a weak relationship between performance on the SAC and the selected neuropsychological tests, so it is likely that these tests assess somewhat different areas of cognitive function. Our correlational findings provide more evidence for using the SAC along with a more complex neuropsychological assessment battery in the evaluation of concussion in young athletes. PMID- 17273467 TI - Perceptions of quality for graduate athletic training education. AB - CONTEXT: Accreditation is generally considered the primary mechanism for quality assurance in higher education, but disagreement often exists between accrediting agencies and the perceptions of professionals who feel the accrediting body has failed to meet its quality control function. For accreditation to have value, it must be a meaningful indicator of quality and be viewed as such. OBJECTIVE: To identify the predominant contributors to quality for postcertification graduate education as perceived by athletic training educators and to compare results among respondents with different education levels, academic ranks, tenure classifications, and program affiliations. DESIGN: Non-experimental descriptive survey. SETTING: 2003 National Athletic Trainers' Association Educators' Conference. Patients or Other Participant(s): Of a convenience sample of 353 athletic training educators, 194 (55%) submitted usable questionnaires. Males accounted for 115 (59%) respondents and females for 79 (41%). Of the 14 National Athletic Trainers' Association-accredited postcertification graduate education programs, 12 were represented. MAIN OUTCOME MEASURE(S): Quantitative data for closed-ended questionnaire items were analyzed using descriptive statistics and measures of central tendency, with composite mean scores for each item used for comparisons. Qualitative data were coded according to major themes and analyzed. RESULTS: Support for accreditation at the postcertification graduate education level was moderate (mean = 3.08 +/- 0.811 on a 4-point scale). Subjects with doctoral degrees (n = 88) indicated that research contributed significantly more to quality (mean = 3.38 +/- 0.636) than did those with master's degrees (n = 106, mean = 2.97 +/- 0.786). Respondents with master's degrees stated that clinical education was a greater contributor to quality (mean = 3.76 +/- 0.491) than did those with doctoral degrees (3.44 +/- 0.663). CONCLUSIONS: The educators showed agreement for most quality indicators. The greatest contributors to program quality were program curriculum; adequate faculty, staff, and administrative support; evaluation; clinical education; and research. PMID- 17273468 TI - Athletic training students in the college/ university setting and the scope of clinical education. AB - CONTEXT: Athletic training education programs must provide the proper type and amount of clinical supervision in order for athletic training students to obtain appropriate clinical education and to meet Board of Certification examination requirements. OBJECTIVE: To assess athletic training students' perceptions of the type and amount of clinical supervision received during clinical education. DESIGN: Cross-sectional design. SETTING: 124 CAAHEP-accredited NCAA institutions. PATIENTS OR OTHER PARTICIPANTS: We obtained a national stratified random sample (by National Athletic Trainers' Association district) of undergraduate athletic training students from 61 Commission on Accreditation of Allied Health Education Programs-accredited athletic training education programs. A total of 851 athletic training students participated in the study. MAIN OUTCOME MEASURE(S): Differences among athletic training students with first-aider/provider qualifications, student supervision during moderate-risk and increased-risk sports, program/institutional characteristics, type and amount of clinical supervision, and students' academic level and mean percentage of time spent in different types of clinical supervision. RESULTS: A total of 276 (32.4%) of the students reported that they supplied medical care and athletic training-related coverage beyond that of a first aider/provider. Athletic training students stating that they traveled with teams without supervision numbered 342 (40.2%). A significant difference was noted between the amount of supervision reported by sophomore and senior students ( P < .01). CONCLUSIONS: Athletic training students do not seem to be receiving appropriate clinical supervision and are often acting outside the scope of clinical education. PMID- 17273469 TI - Baseline values of trunk endurance and hip strength in collegiate athletes. AB - CONTEXT: Injuries involving the lumbar spine and lower extremities in athletes are among the most disabling. Lack of trunk and hip strength may predispose athletes to such injuries. OBJECTIVE: To measure trunk endurance and hip strength in a population of National Collegiate Athletic Association Division III athletes. DESIGN: Cross-sectional design of 5 collegiate athletic teams. SETTING: An athletic training facility during preparticipation physical examinations. PATIENTS OR OTHER PARTICIPANTS: 105 Division III athletes. MAIN OUTCOME MEASURE(S): The series of tests included the 60-second back-extension endurance and 60-second tall-kneeling tests. The scores of these tests were reported in repetitions. A handheld dynamometer was used to measure maximal hip external rotation strength bilaterally. The double-leg lowering test was measured in degrees, and the Star Excursion Balance Test was measured in 4 directions as a percentage of the subject's leg length. Descriptive statistics were calculated for each exercise and each team. RESULTS: The average score for the 60-second back-extension endurance test was 53 +/- 13 repetitions. The 60-second tall kneeling test had an average score of 30 +/- 8 repetitions. For the 2 hip external-rotation strength tests, the average score was 7 +/- 4 kg (12% +/- 6% of body weight). Average scores were 50 degrees +/- 10 degrees for the double-leg lowering test and 94 +/- 9 cm (105% +/- 9 % of leg length) for the Star Excursion Balance Test. CONCLUSIONS: The descriptive data from these trunk and hip tests allow for the development of baseline values for each test. By investigating these measures in an athletic population, we hope to provide health care professionals with further insights about the trunk and hip muscle performance in athletes to prevent and rehabilitate athletic injuries. PMID- 17273470 TI - Alcohol consumption behaviors among athletic training students at accredited athletic training education programs in the mid-america athletic trainers' association. AB - CONTEXT: Alcohol consumption among college students has been evaluated at many levels, but assessment of alcohol consumption among collegiate athletic training students has not been substantially reviewed. Understanding the alcohol use of this college-age group adds to the overall literature on alcohol consumption of the college student population. OBJECTIVE: To assess the prevalence of hazardous and harmful alcohol consumption behaviors in collegiate athletic training students using the Alcohol Use Disorders Identification Test (AUDIT). DESIGN: A cross-sectional survey using the AUDIT. SETTING: The AUDIT questionnaire was sent to the program directors of all Commission on Accreditation of Allied Health Education Programs-accredited athletic training education programs in the Mid America Athletic Trainers' Association. PATIENTS OR OTHER PARTICIPANTS: Fourteen of the 35 athletic training education programs agreed to take part in the study, yielding a 40% response rate. Three hundred and forty-eight of the 946 athletic training students (36%) solicited agreed to participate. MAIN OUTCOME MEASURE(S): Maximum score on the AUDIT out of a possible score of 40. RESULTS: The mean AUDIT score for the sample was 7.47, with an SD of 5.69. Thirty-seven percent of participants demonstrated an AUDIT score of 9 or above. Nearly 18% of participants reported having 6 or more drinks at one sitting on a weekly basis. CONCLUSIONS: It is difficult to compare athletic training students' alcohol consumption with that of other student groups. The greater percentage of athletic training students does not drink in excess on a frequent basis. PMID- 17273471 TI - Injuries sustained by pediatric ice hockey, lacrosse, and field hockey athletes presenting to United States emergency departments, 1990-2003. AB - CONTEXT: Ice hockey, lacrosse, and field hockey are increasingly popular sports among US youth athletes, but no authors to date have compared injuries in male and female pediatric (ages 2 through 18 years) participants. OBJECTIVE: To compare patterns of injury among pediatric ice hockey, lacrosse, and field hockey players. DESIGN: A descriptive analysis of all pediatric (ages 2 through 18 years) ice hockey, lacrosse, and field hockey injuries captured by the US Consumer Product Safety Commission's National Electronic Injury Surveillance System. SETTING: US Consumer Product Safety Commission's National Electronic Injury Surveillance System. PATIENTS OR OTHER PARTICIPANTS: Children with ice hockey, lacrosse, or field hockey injuries presenting to emergency departments participating in the National Electronic Injury Surveillance System. MAIN OUTCOME MEASURES(S): We reviewed all ice hockey, lacrosse, and field hockey injuries captured by the National Electronic Injury Surveillance System and categorized them by sex, age, injury site, and injury diagnosis. RESULTS: An estimated 321 237 pediatric participants in ice hockey, lacrosse, and field hockey presented to US emergency departments from 1990 through 2003. The injured were primarily male (74.4%) and aged 10 through 18 years (95.4%). Ice hockey accounted for more injuries (53.6%) than lacrosse (26.5%) or field hockey (19.9%). Children aged 2 through 9 years sustained twice the proportion of head and face injuries (53.1%) as children aged 10 through 18 years (23.2%) (incidence rate ratio [IRR] = 2.25, 95% confidence interval [CI] = 1.94 to 2.62). Males incurred a higher proportion of shoulder and upper arm injuries (14.1%) than females (3.1%) (IRR = 4.51, 95% CI = 3.07 to 6.62). The proportion of concussion was higher in ice hockey players (3.9%) than in field hockey players (1.4%) (IRR = 2.75, 95% CI = 1.17 to 6.46). Females in lacrosse had twice the proportion of facial injuries (20.9%) as males (10.5%) (IRR = 1.95, 95% CI = 1.46 to 2.60). In all sports, the ball or puck caused a greater proportion of face injuries in females than in males (IRR = 2.48, 95% CI = 2.03 to 3.05). Facial injuries from falls occurred in higher proportions in ice hockey players (10.6%) than in lacrosse (2.4%) (IRR = 4.32, 95% CI = 1.53 to 12.18) and field hockey (0.4%) players (IRR = 28.38, 95% CI = 6.71 to 120.01). CONCLUSIONS: Pediatric ice hockey, lacrosse, and field hockey injuries differed by age and sport and, within each sport, by sex. An understanding of sport-specific patterns of injury should assist coaches and certified athletic trainers in developing targeted preventive interventions. PMID- 17273472 TI - Neuromuscular control training programs and noncontact anterior cruciate ligament injury rates in female athletes: a numbers-needed-to-treat analysis. AB - OBJECTIVE: To determine the numbers needed to treat (NNT) and relative risk reduction (RRR) associated with neuromuscular training programs aimed at preventing noncontact anterior cruciate ligament (ACL) injuries in female athletes. DATA SOURCES: We searched PubMed, MEDLINE, SPORT Discus, CINAHL, and Web of Science from 1966 through 2005 using the terms knee, injury, anterior cruciate ligament, ACL, prevention, plyometric, and neuromuscular training. STUDY SELECTION: Selected articles were from peer-reviewed journals written in English that described original research studies comparing neuromuscular training programs with control programs to determine the number of noncontact ACL injuries per event exposure or hours of playing time. Five studies met the inclusion criteria and were independently rated by 3 reviewers using the Physiotherapy Evidence Database (PEDro) scale. Consensus PEDro scores ranged from 4 to 7 out of 10. DATA EXTRACTION: We used numbers of subjects, ACL injuries, and injury exposure rates to calculate NNT and RRR for each study. The NNT calculations from all studies were based on the number of players across 1 competitive season and were described as NNT benefit or NNT harm. DATA SYNTHESIS: All 5 studies demonstrated a prophylactic effect due to the neuromuscular training programs. The pooled NNT estimates showed that 89 individuals (95% confidence interval: 66 to 136) would need to participate in the prophylactic training program to prevent 1 ACL injury over the course of 1 competitive season. Pooled RRR was 70% (95% confidence interval: 54% to 80%) among individuals who participated in the intervention program. One high-quality randomized control trial and 4 medium quality prospective cohort studies showed mostly consistent findings. Thus, a Strength of Recommendation Taxonomy level of evidence of 1 with a grade B recommendation supports the use of neuromuscular training programs in the prevention of noncontact ACL injuries in female athletes. PMID- 17273474 TI - Preventing and treating lower extremity stress reactions and fractures in adults. PMID- 17273473 TI - The dual roles of neutrophils and macrophages in inflammation: a critical balance between tissue damage and repair. AB - OBJECTIVE: To discuss the acute phase of inflammatory response with a focus on the neutrophilic response and its role in inflammation. We discuss the relative balance between the need for inflammation to stimulate repair and the need to limit inflammation because of the additional damage it causes. DATA SOURCES: We conducted a MEDLINE search from 1966 to 2005 for literature related to acute inflammation, muscle injury, and repair using combinations of the key words inflammation, neutrophil, macrophage, and cytokines. Additional literature was acquired through cross-referencing of bibliographies of articles obtained through the MEDLINE searches. DATA SYNTHESIS: We reviewed more than 200 relevant articles. Although neutrophils are an important cell population in acute inflammation, few athletic trainers are familiar with the neutrophil's actions or its dichotomous role as both perpetrator of tissue damage and initiator of repair. Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage by macrophages. These actions are orchestrated by numerous cytokines and the expression of their receptors, which represent a potential means for inhibiting selective aspects of inflammation. CONCLUSIONS: Neutrophils infiltrate injured tissues but can also be present after noninjurious exercise. These cells have both specific and nonspecific defensive immune system functions that can cause tissue damage in isolation or as sequelae to other tissue injury. It might seem that limiting the action of neutrophils would be clinically beneficial, but these cells are also responsible for initiating the reparative process that is later managed by macrophages. Although achieving a therapeutic balance between limiting inflammation and stimulating repair is important, the duplicitous roles of neutrophils and macrophages in both the inflammation and healing processes create a physiologic paradox for clinicians whose goals are to limit inflammation and to stimulate healing after acute soft tissue injury. PMID- 17273482 TI - Residents only, please. PMID- 17273475 TI - Contact sport concussion incidence. PMID- 17273483 TI - Asthma control and management in the community: indices in 1997 compared with indices in 2002. AB - OBJECTIVE: To determine whether there was any change in indices of asthma control in population-based samples of patients with asthma between 1997 and 2002. DESIGN: We examined asthma control and treatment in the community using two cross sectional studies carried out 5 years apart in 1997 and 2002. Pharmacists handed out the questionnaires to patients with asthma; patients completed the questionnaires themselves. SETTING: Community pharmacies in Alberta. PARTICIPANTS: Patients with physician-confirmed asthma attending pharmacies to fill prescriptions for asthma medications. MAIN OUTCOME MEASURE: Asthma control. RESULTS: In 1997 and 2002, 301 and 340 completed questionnaires were received, respectively. Mean age of respondents was 42 and 39 years and the female-to-male ratio was 1.3:1 and 1.4:1, respectively. Overall asthma control was achieved by 27% (1997) and 31% (2002) of subjects, a non-significant change. Regular inhaled corticosteroid use was reported by 63% (1997) and 65% (2002) of subjects; mean daily dose of inhaled corticosteroids reported decreased from 920 mug in 1997 to 765 mug in 2002 (P < .02), which might reflect adoption of the newer guideline recommendation for lower-dose inhaled corticosteroids in combination therapy rather than a decrease in severity of asthma. Fewer respondents reported being hospitalized for asthma in 2002 (P = .02). Self-management plans were used by 7% and 5% of subjects in 1997 and 2002, respectively. CONCLUSION: In general, asthma control and use of inhaled corticosteroids was similar in 1997 and 2002. There was no evidence that patient education on asthma had increased. Asthma control was poor in 1997 and had not improved by 2002. PMID- 17273484 TI - Medical directors of long-term care facilities: preventing another physician shortage? AB - OBJECTIVE: The long-term care (LTC) sector in Canada is expanding, but little attention has been given to medical human resources in this area. Our objective was to seek LTC medical directors' opinions about medical services in LTC and about strategies for recruitment and retention. DESIGN: Mailed survey. SETTING: Long-term care facilities and nursing homes. PARTICIPANTS: Seven hundred five medical directors of LTC facilities across Canada were identified from the Canadian Healthcare Association database. MAIN OUTCOME MEASURES: Responses to open- and closed-ended questions and to Likert-type scales. RESULTS: The response rate was 55%. The average age of medical directors was 54 years. Most had started work in LTC because of a vacant position, as opposed to self-perceived skills or training. Most (75.3%) reported satisfaction with their role as medical directors, but 82.7% believed that there was a significant shortage of physicians working in LTC, and 42% had seriously considered leaving their positions. Major sources of satisfaction identified were clinical, especially working with older patients and improving care. Important sources of dissatisfaction were remuneration for LTC work, on-call coverage, and excessive paperwork. Directors suggested increases to fee schedules as the main recruitment and retention strategy, and many believed that increasing exposure to LTC during residency would increase recruitment. Development of larger on-call groups for coverage and alternative methods of remuneration were not cited as important factors. Most did not believe that working in a teaching nursing home would increase their satisfaction. Directors did not think the use of nurse practitioners would alleviate concerns about shortages of physicians. CONCLUSION: Medical directors of LTC facilities are aging, and many are considering leaving their work in LTC. Without an increase in the number of physicians willing to work in LTC institutions, the current shortage of LTC physicians could increase in the near future. Medical directors' responses to questions could help guide strategies to recruit and retain physicians. Future areas of research should include the perspectives of physicians who are not medical directors and of family medicine residents. PMID- 17273485 TI - Continuity of care for older patients in family practice: how important is it? AB - OBJECTIVE: To examine the evidence that continuity of primary care is important for older people with chronic diseases. DATA SOURCES: MEDLINE, EMBASE and CINAHL were searched from January 1970 to June 2005 for original articles in English that examined the relationship between interpersonal continuity of patient care and health outcomes of people 50 years old and older. Articles found were reviewed and analyzed by both authors to assess the strength of study design and the quality of the evidence provided. STUDY SELECTION: We used the search terms "continuity of patient care," "elderly," "primary care," and "outcomes." Criteria from the Canadian Task Force on Preventive Health Care were used to assess the quality of studies; only studies providing levels I to III evidence were included in this review. SYNTHESIS: Of 7563 articles found, we chose 99 studies (and 27 other studies cited in them) by studying their abstracts. Assessment of these 126 studies indicated that only 5 were of good quality and relevant to the inquiry. Two of these 5 were randomized controlled trials, and 3 were observational studies. CONCLUSION: Although the literature on continuity of care generally suggests that continuity of interpersonal primary care is important and beneficial, specific evidence that it is beneficial for elderly people is scanty. There is a need for well designed studies to investigate this issue. PMID- 17273487 TI - Collaboration between primary care and psychiatric services: does it help family physicians? AB - OBJECTIVE: To compare family physicians' reports of their experiences managing patients with psychiatric disorders in settings with and without access to collaborative mental health services. DESIGN: Survey using a questionnaire adapted from a similar study in Australia. Family physicians were asked about their knowledge, skills, and degree of comfort in managing the following psychiatric disorders derived from the primary care version of the 10th edition of the International Classification of Diseases: psychosis, depression, anxiety, childhood disorders, and stress-related disorders. We also compared the 2 groups of physicians regarding their satisfaction with mental health services in general. SETTING: The Capital District Health Authority (CDHA) in Nova Scotia. PARTICIPANTS: All family physicians practising in the CDHA. MAIN OUTCOME MEASURES: Self-reported knowledge, skills, and degree of comfort in managing psychiatric problems; satisfaction with mental health services, adjusted for family physicians' demographics; and stated interest in mental health. RESULTS: We received 101 responses (37 from physicians with access to collaborative care and 64 from physicians without access) from 7 communities in the CDHA. Family physicians who had access to collaborative care reported significantly greater knowledge in the areas of psychosis, alcohol or substance use, and childhood behavioural problems; and better skills in managing psychosis, alcohol or substance use, childhood depression or anxiety, childhood behavioural disorders, and relationship problems. Their comfort levels in managing relationship problems and childhood behavioural disorders were also significantly higher. Family physicians with access to collaborative care were significantly more satisfied with mental health services, over and above shared care. All these differences remained significant after controlling for sex, level of interest in mental health, and years in practice. CONCLUSION: Family physicians with access to collaborative care reported greater knowledge, better skills, and more comfort in managing psychiatric disorders and greater satisfaction with mental health services. Further work is needed to establish why this is so and to determine any effect on patient outcomes, such as symptoms, quality of life, and psychosocial functioning. PMID- 17273488 TI - Managing depression in primary care: community survey. AB - OBJECTIVE: To investigate family physicians' practice patterns for managing depression and mental health concerns among adolescent and adult patients. DESIGN: Cross-sectional survey. SETTING: London, Ont, a mid-sized Canadian city. PARTICIPANTS: One hundred sixty-three family physicians identified through the London and District Academy of Medicine. MAIN OUTCOME MEASURES: Practice patterns for managing depression, including screening, pharmacotherapy, psychotherapy, shared care, and training needs. RESULTS: Response rate was 63%. Family physicians reported spending a substantial portion of their time during patient visits (26% to 50%) addressing mental health issues, with depression being the most common issue (51% to 75% of patients with mental health issues). About 40% of respondents did routine mental health screening, and 60% screened patients with risk factors for depression. Shared care with mental health professionals was common (care was shared for 26% to 50% of patients). Physicians and patients were moderately satisfied with shared care, but were frustrated by long waiting lists and communication barriers. Most physicians provided psychotherapy to patients in the form of general advice. Differences in practice patterns were observed; physicians treated more adults than adolescents with depression, and they reported greater comfort in treating adults. Although 33% of physicians described using cognitive behavioural therapy (CBT), they reported having little training in CBT. Moderate interest was expressed in CBT training, with a preference for a workshop format. CONCLUSION: Although 40% of family physicians routinely screen patients for mental health issues, depression is often not detected. Satisfaction with shared care can be increased through better communication with mental health professionals. Physicians' management of adolescent patients can be improved by further medical training, consultation, and collaboration with mental health professionals. Training in evidence-based treatment of depression is particularly warranted given physicians' limited knowledge of CBT. PMID- 17273490 TI - Deciding on stimulant use for childhood ADHD: maintaining focus on the key questions. PMID- 17273491 TI - A good fit: integrating physical activity counselors into family practice. PMID- 17273492 TI - Resources for palliative care. PMID- 17273494 TI - Role for primary care in epidemic surge capacity. PMID- 17273493 TI - Evaluating procedural skills. PMID- 17273495 TI - What's in it for me? PMID- 17273496 TI - Patches of hair loss on the scalp. PMID- 17273497 TI - Direct ophthalmoscopic examination of the eyes: does a mydriatic agent help with diagnosis? PMID- 17273498 TI - Approach to attention deficit disorder in adults. AB - OBJECTIVE: To review the etiology, diagnosis, and management of attention deficit disorder (ADD) in adults. SOURCES OF INFORMATION: PsycINFO, PubMed, and Psychiatry 24x7.com were searched. Several books on ADD in adults were reviewed. I also drew on my own clinical experience assessing and treating adults with ADD for more than 20 years. MAIN MESSAGE: The classic triad of ADD symptoms are inattention, impulsiveness, and hyperactivity or restlessness. Although ADD is a well established brain disorder, the diagnosis remains controversial. Attention deficit disorder has been called a fad, not a legitimate diagnosis, but it is a well established, well documented, medical condition that can cause much suffering if left untreated. At one time we thought children would outgrow ADD at puberty, but we now know that many will continue to have residual symptoms throughout adolescence and adulthood. If left untreated, ADD can interfere with relationships, employment, and self-esteem. Treatment with stimulants and adjunctive care is often effective. CONCLUSION: Attention deficit disorder in adults represents a substantial burden of illness. It can be diagnosed and treated successfully. PMID- 17273499 TI - Case Report: infected ear cartilage piercing. PMID- 17273500 TI - Lifetime exposure to radiation from imaging investigations. AB - OBJECTIVE: To assess levels of radiation exposure from diagnostic imaging among family practice patients, the degree to which these levels exceed recommended levels, and whether radiation exposure level is associated with a diagnosis of cancer. DESIGN: Chart abstraction. SETTING: Six practices in an academic family medicine centre and 1 family practice in the community. PARTICIPANTS: Two hundred fifty patients between the ages of 45 and 65 years with at least 20 years' information on their charts. MAIN OUTCOME MEASURES: All x-ray procedures, the dates they were performed, the amount of radiation exposure from each procedure based on standard charts, and whether diagnosis of any form of cancer was noted on the chart. RESULTS: Mean lifetime radiation exposure was 14.94 mSv. No patients had exceeded the lifetime occupational limit of 400 mSv; however, 4.4% of patients had exceeded the annual occupational exposure limit of 20 mSv at some point in their lives. Mean lifetime exposure of those with cancer was found to be significantly higher than exposure of those without cancer. This difference was due to the extra radiation exposure after the cancer was diagnosed; hence a causal relationship was not shown. Mean level of annual radiation exposure from diagnostic imaging has been slowly increasing since the 1960s. CONCLUSION: The current lifetime level of radiation to which patients are exposed by diagnostic imaging appears to be far below the maximum recommended level. Some patients do exceed the maximum recommended annual level, but this overexposure is generally warranted due to serious medical illness or injury, and the benefit outweighs the risk. We found no evidence of an association between these low levels of radiation and development of cancer. PMID- 17273501 TI - Psychological sequelae of acne vulgaris: results of a qualitative study. AB - OBJECTIVE: To investigate the psychological sequelae of acne vulgaris. DESIGN: Qualitative study using a grounded-theory approach. SETTING: General practices and specialty dermatology practices in Newcastle, Australia. PARTICIPANTS: Patients with current acne recruited from the practices. METHOD: We used semistructured interviews and recorded participants' comments verbatim. Data analysis was cumulative and concurrent throughout the data-collection period. Coding and analysis was done in the inductive tradition. MAIN FINDINGS: Interviews were conducted with 26 subjects who represented a range of ages and acne severity. Psychological morbidity was considerable. Though participants had mood and anxiety symptoms, these symptoms tended to be subsyndromal and evanescent. More prominent symptoms were embarrassment, impaired self-image, low self-esteem, self-consciousness, frustration, and anger. Some subjects thought that acne had affected their personalities permanently and adversely. Psychological sequelae were attributed to the effects of facial acne on appearance. CONCLUSION: The psychological effects of acne can be considerable. The psychological morbidity is complex and often does not conform to standard psychiatric disease criteria. Recognition and management of the psychological sequelae of acne by general practitioners is of considerable importance. PMID- 17273502 TI - Training in adolescent health: how much have second-year residents had? AB - OBJECTIVE: To determine the level of training second-year family medicine residents have had in adolescent medicine. DESIGN: Web-based survey. SETTING: Canadian family medicine residency programs. PARTICIPANTS: English-speaking second-year family medicine residents. MAIN OUTCOME MEASURES: Residents' self reported levels of training in adolescent health, specifically, the types of formal and informal education in adolescent health provided by family medicine residency programs. Residents' self-reported comfort in dealing with common health problems in adolescence was also examined. RESULTS: Responses were received from 78 residents representing 11 different programs across Canada. About 38.5% of family medicine residents had attended lectures on adolescent health. Only 37.2% of residents felt comfortable with their knowledge of adolescent health. Respondents indicated that most of their education in adolescent health occurred during family medicine rotations. Only 24% of respondents supplemented their training with attendance at school-based or reproductive health clinics. CONCLUSION: Learning how to deal effectively with teenagers should be an essential part of family medicine training, yet family medicine residents receive only a small amount of exposure to adolescent health issues in primary care settings. Few residents attend school-based or reproductive health clinics even though such activity is recommended by the College of Family Physicians of Canada. A more structured adolescent health experience in family medicine residency would help ensure that Canadian adolescents benefit from informed and experienced family physicians. PMID- 17273503 TI - Metabolic syndrome in a family practice population: prevalence and clinical characteristics. AB - OBJECTIVE: To determine the prevalence and clinical characteristics of metabolic syndrome in a family practice population. DESIGN: Chart abstraction and patient interviews. SETTING: Family Medicine Centre in Kingston, Ont. PARTICIPANTS: Five hundred one men and women between 40 and 60 years old registered at the Family Medicine Centre. Based on the number of risk factors for metabolic syndrome recorded on their charts (except for waist circumference), participants were stratified into 3 groups. Group 1 were patients without the syndrome (0 or 1 risk factor). Group 2 were patients who might have the syndrome, depending on subsequent measurement of waist circumference (2 risk factors). Group 3 were patients with metabolic syndrome (3 or more risk factors). Patients in group 2 were invited to attend the clinic for an assessment of waist circumference. MAIN OUTCOME MEASURES: Presence of metabolic syndrome, as defined by the Third Adult Treatment Panel of the National Institutes of Health, based on waist circumference; blood pressure; and serum triglyceride, high-density lipoprotein, and glucose levels. RESULTS: Prevalence of metabolic syndrome in this population was 33% (35% among men and 32% among women). Hypertension was the most prevalent component of the syndrome (81.6%). The most common combination of 3 components of the syndrome was central obesity, hypertriglyceridemia, and hypertension (43.7%). CONCLUSION: Metabolic syndrome was prevalent among patients in the family practice studied. One in every 3 patients between 40 and 60 years old met the criteria for the syndrome. PMID- 17273546 TI - Drug designed to raise HDL levels falls down. PMID- 17273547 TI - Passing the baton--to whom? AB - Scientific discovery occasionally occurs as a sudden and dramatic leap ahead but more often proceeds at a subtler and steadier pace. Each small step forward may escape public notice but is ultimately vital to the journey's success. Indeed, such gradual advancement represents the collective contributions of many workers in the field, some new to the journey. While the notion of combined effort and multiple contributors is honorable, it poses an inherent danger. In our society, unproven, unorthodox, or unnoticed researchers may not receive the funding or support needed to make their contributions. Furthermore, even if they have the potential to make a leap, a hostile environment may preclude their doing so. This article concentrates on the looming crisis in diabetes research, but the principles pertain to all fields of clinical and biomedical science. PMID- 17273549 TI - A little stress is good: IFN-gamma, demyelination, and multiple sclerosis. AB - The exact role(s) of the cytokine IFN-gamma in the demyelinating disease multiple sclerosis remain controversial, with evidence suggesting both detrimental and protective effects of the cytokine in MS and MS models such as EAE. The study by Lin and coworkers in this issue of the JCI produces evidence that protective effects of IFN-gamma on mature oligodendrocytes during EAE induction are mediated via activation of the pancreatic ER kinase (PERK), resulting in induction of the endoplasmic reticular stress response pathway (see the related article beginning on page 448). Modulation of this stress pathway has what we believe to be novel therapeutic potential for MS. PMID- 17273550 TI - Notch: a mastermind of vascular morphogenesis. AB - The way in which multiple cell types organize themselves into a carefully sculpted, 3D labyrinth of vessels that regulate blood flow throughout the body has been a longstanding mystery. Clinicians familiar with congenital cardiovascular disease recognize how genetic variants and modest perturbations in this complex set of spatiotemporal interactions and stochastic processes can result in life-threatening anomalies. Although the mystery is not yet fully solved, we are poised at an exciting juncture, as insights from murine disease models are converging with advances in human genetics to shed new light on puzzling clinical phenotypes of vascular disease. The study by High et al. in this issue of the JCI establishes a model system that mimics clinical features of congenital cardiovascular disease and further defines the role of the Notch signaling pathway in the neural crest as an essential determinant of cardiovascular structure (see the related article beginning on page 353). PMID- 17273548 TI - Physiology and immunology of the cholinergic antiinflammatory pathway. AB - Cytokine production by the immune system contributes importantly to both health and disease. The nervous system, via an inflammatory reflex of the vagus nerve, can inhibit cytokine release and thereby prevent tissue injury and death. The efferent neural signaling pathway is termed the cholinergic antiinflammatory pathway. Cholinergic agonists inhibit cytokine synthesis and protect against cytokine-mediated diseases. Stimulation of the vagus nerve prevents the damaging effects of cytokine release in experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, arthritis, and other inflammatory syndromes. Herein is a review of this physiological, functional anatomical mechanism for neurological regulation of cytokine-dependent disease that begins to define an immunological homunculus. PMID- 17273551 TI - An intrinsic host defense against HIV-1 integration? AB - HSCs are one of only a few cell types that resist HIV-1 infection despite the presence of HIV-1 receptors. An increasing number of genes have been identified that can reduce the sensitivity of cultured cells to retrovirus infection, and in this issue of the JCI, Zhang et al. identify p21(Waf1/Cip1/Sdi1) (p21) as a gene product that can influence the sensitivity of HSCs to HIV-1 infection (see the related article beginning on page 473). Strikingly, p21 appears to alter the fate of nuclear HIV-1 DNA, promoting the formation of circular viral DNA forms rather than functional proviruses. PMID- 17273552 TI - Transcriptional regulation of epithelial-mesenchymal transition. AB - It has become increasingly obvious that the notion of a terminally differentiated cell is likely a simplified concept. Epithelial-mesenchymal transition (EMT), during which epithelial cells assume a mesenchymal phenotype, is a key event occurring during normal development and pathological processes. Multiple extracellular stimuli and transcriptional regulators can trigger EMT, but how such distinct signaling pathways orchestrate the complex cellular events that facilitate EMT is not well understood. In this issue of the JCI, Venkov et al. report on their examination of fibroblasts resulting from EMT and describe a novel protein-DNA complex that is essential for transcription of fibroblast specific protein 1 (FSP1) and sufficient to induce early EMT events (see the related article beginning on page 482). Collectively, their results suggest that this complex is an important regulator of the EMT transcriptome. PMID- 17273554 TI - A link between protein translation and body weight. AB - Nutrient overload induces obesity, a primary risk factor for type 2 diabetes. Ribosomal biogenesis and protein synthesis, which are controlled by the mammalian target of rapamycin (mTOR), are primary energy-consuming processes in cells. mTOR phosphorylates and inactivates members of the eukaryotic translation initiation factor 4E-binding (eIF4E-binding) protein (4E-BP) family, which are translational repressors of 5' cap-dependent protein synthesis. In this issue of the JCI, Le Bacquer et al. report that simultaneous deletion of both 4E-BP1 and 4E-BP2 in mice results in insulin resistance, decreased energy expenditure, and increased adipogenesis (see the related article beginning on page 387). These findings link protein synthesis, insulin sensitivity, and body weight. PMID- 17273553 TI - To ablate or not to ablate? HSCs in the T cell driver's seat. AB - The combination of the induction of lymphopenia and vaccination and/or T cell transfer is garnering much attention for cancer treatment. Preclinical studies have shown that the induction of lymphopenia by chemotherapy or radiation can enhance the antitumor efficacy of several distinct, cell-based immunotherapeutic approaches. The mechanism(s) by which such enhancement is achieved are being intensively studied, yet there is much opportunity for improvement. The animal studies reported by Wrzesinski and colleagues in this issue of the JCI are a promising and timely step in this direction (see the related article beginning on page 492). The authors have evaluated both the effect of increasing the intensity of lymphodepletion and the influence of HSC transfer on the in vivo function of adoptively transferred CD8(+) T cells. We discuss their results in light of the evolving field and their implications for advancing cell-based immunotherapies for cancer. PMID- 17273555 TI - An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. AB - The cardiac outflow tract develops as a result of a complex interplay among several cell types, including cardiac neural crest cells, endothelial cells, and cardiomyocytes. In both humans and mice, mutations in components of the Notch signaling pathway result in congenital heart disease characterized by cardiac outflow tract defects. However, the specific cell types in which Notch functions during cardiovascular development remain to be defined. In addition, in vitro studies have provided conflicting data regarding the ability of Notch to promote or inhibit smooth muscle differentiation, while the physiological role for Notch in smooth muscle formation during development remains unclear. In this study, we generated mice in which Notch signaling was specifically inactivated in derivatives of the neural crest. These mice exhibited cardiovascular anomalies, including aortic arch patterning defects, pulmonary artery stenosis, and ventricular septal defects. We show that Notch plays a critical, cell-autonomous role in the differentiation of cardiac neural crest precursors into smooth muscle cells both in vitro and in vivo, and we identify specific Notch targets in neural crest that are implicated in this process. These results provide a molecular and cellular framework for understanding the role of Notch signaling in the etiology of congenital heart disease. PMID- 17273556 TI - Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2. AB - The most common pathology associated with obesity is insulin resistance, which results in the onset of type 2 diabetes mellitus. Several studies have implicated the mammalian target of rapamycin (mTOR) signaling pathway in obesity. Eukaryotic translation initiation factor 4E-binding (eIF4E-binding) proteins (4E-BPs), which repress translation by binding to eIF4E, are downstream effectors of mTOR. We report that the combined disruption of 4E-BP1 and 4E-BP2 in mice increased their sensitivity to diet-induced obesity. Increased adiposity was explained at least in part by accelerated adipogenesis driven by increased expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), C/EBPalpha, and PPARgamma coupled with reduced energy expenditure, reduced lipolysis, and greater fatty acid reesterification in the adipose tissue of 4E-BP1 and 4E-BP2 double KO mice. Increased insulin resistance in 4E-BP1 and 4E-BP2 double KO mice was associated with increased ribosomal protein S6 kinase (S6K) activity and impairment of Akt signaling in muscle, liver, and adipose tissue. These data clearly demonstrate the role of 4E-BPs as a metabolic brake in the development of obesity and reinforce the idea that deregulated mTOR signaling is associated with the development of the metabolic syndrome. PMID- 17273557 TI - The integrated stress response prevents demyelination by protecting oligodendrocytes against immune-mediated damage. AB - In response to ER stress, the pancreatic endoplasmic reticulum kinase (PERK) coordinates an adaptive program known as the integrated stress response (ISR) by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha). IFN-gamma, which activates the ER stress response in oligodendrocytes, is believed to play a critical role in the immune-mediated CNS disorder multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). Here we report that CNS delivery of IFN-gamma before EAE onset ameliorated the disease course and prevented demyelination, axonal damage, and oligodendrocyte loss. The beneficial effects of IFN-gamma were accompanied by PERK activation in oligodendrocytes and were abrogated in PERK-deficient animals. Our results indicate that IFN-gamma activation of PERK in mature oligodendrocytes attenuates EAE severity and suggest that therapeutic approaches to activate the ISR could prove beneficial in MS. PMID- 17273558 TI - Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function. AB - Inhalation of iloprost, a stable prostacyclin (PGI(2)) analog, is a well-accepted and safe treatment for pulmonary arterial hypertension. Although iloprost mainly acts as a vasodilator by binding to the I prostanoid (IP) receptor, recent evidence suggests that signaling via this receptor also has antiinflammatory effects through unclear mechanisms. Here we show in a murine model of asthma that iloprost inhalation suppressed the cardinal features of asthma when given during the priming or challenge phase. As a mechanism of action, iloprost interfered with the function of lung myeloid DCs, critical antigen-presenting cells of the airways. Iloprost treatment inhibited the maturation and migration of lung DCs to the mediastinal LNs, thereby abolishing the induction of an allergen-specific Th2 response in these nodes. The effect of iloprost was DC autonomous, as iloprost treated DCs no longer induced Th2 differentiation from naive T cells or boosted effector cytokine production in primed Th2 cells. These data should pave the way for a clinical effectiveness study using inhaled iloprost for the treatment of asthma. PMID- 17273559 TI - Primitive hematopoietic cells resist HIV-1 infection via p21. AB - Hematopoietic stem cells are resistant to HIV-1 infection. Here, we report a novel mechanism by which the cyclin-dependent kinase inhibitor (CKI) p21(Waf1/Cip1/Sdi1) (p21), a known regulator of stem cell pool size, restricts HIV-1 infection of primitive hematopoietic cells. Modifying p21 expression altered HIV-1 infection prior to changes in cell cycling and was selective for p21 since silencing the related CKIs, p27(Kip1) and p18(INK4C), had no effect on HIV-1. We show that p21 blocked viral infection by complexing with HIV-1 integrase and aborting chromosomal integration. A closely related lentivirus with a distinct integrase, SIVmac-251, and the other cell-intrinsic inhibitors of HIV 1, Trim5alpha, PML, Murr1, and IFN-alpha, were unaffected by p21. Therefore, p21 is an endogenous cellular component in stem cells that provides a unique molecular barrier to HIV-1 infection and may explain how these cells remain an uninfected "sanctuary" in HIV disease. PMID- 17273561 TI - Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8 T cells. AB - Depleting host immune elements with nonmyeloablative regimens prior to the adoptive transfer of tumor-specific CD8(+) T cells significantly enhances tumor treatment. In the current study, superior antitumor efficacy was achieved by further increasing the intensity of lymphodepletion to a level that required HSC transplantation. Surprisingly, the HSC transplant and not the increased lymphodepletion caused a robust expansion of adoptively transferred tumor specific CD8(+) T cells. The HSC-driven cell expansion of effector, but not of naive, CD8(+) T cells was independent of in vivo restimulation by MHC class I expressing APCs. Simultaneously, HSCs also facilitated the reconstitution of the host lymphoid compartment, including inhibitory elements, not merely via the production of progeny cells but by enhancing the expansion of cells that had survived lymphodepletion. Profound lymphodepletion, by myeloablation or by genetic means, focused the nonspecific HSC boost preferentially toward the transferred tumor-specific T cells, leading to successful tumor treatment. These findings indicate that CD8(+) T cell-mediated tumor responses can be efficiently driven by HSCs in the myeloablative setting and have substantial implications for the design of new antitumor immunotherapies. PMID- 17273560 TI - A proximal activator of transcription in epithelial-mesenchymal transition. AB - Epithelial-mesenchymal transition (EMT) is an important mechanism for phenotypic conversion in normal development and disease states such as tissue fibrosis and metastasis. While this conversion of epithelia is under tight transcriptional control, few of the key transcriptional proteins are known. Fibroblasts produced by EMT express a gene encoding fibroblast-specific protein 1 (FSP1), which is regulated by a proximal cis-acting promoter element called fibroblast transcription site-1 (FTS-1). In mass spectrometry, chromatin immunoprecipitation, and siRNA studies, we used FTS-1 as a unique probe for mediators of EMT and identified a complex of 2 proteins, CArG box-binding factor A (CBF-A) and KRAB-associated protein 1 (KAP-1), that bind this site. Epithelial cells engineered to conditionally express recombinant CBF-A (rCBF-A) activate the transcription of FSP1 and undergo EMT. The FTS-1 response element also exists in the promoters modulating a broader EMT transcriptome, including Twist, and Snail, as well as E-cadherin, beta-catenin, ZO 1, vimentin, alpha1(I) collagen, and alpha-smooth muscle actin, and the induction of rCBF-A appropriately alters their expression as well. We believe formation of the CBF-A/KAP-1/FTS-1 complex is sufficient for the induction of FSP1 and a novel proximal activator of EMT. PMID- 17273563 TI - Evaluation of quality of life of patients submitted to pulmonary resection due to neoplasia. AB - OBJECTIVE: To evaluate the health-related quality of life of patients submitted to resection of the pulmonary parenchyma due to neoplasia. METHODS: The Medical Outcomes Study 36-item Short-Form Health Survey was used to evaluate patients in the preoperative period and on postoperative days 30, 90 and 180. We used the GEE statistical model, in which the dependent variable (quality of life) changes for each patient over the course of the evaluation. Independent variables were gender, age, educational level, type of surgery, radiotherapy, chemotherapy, forced vital capacity and 6-minute walk test. The level of significance adopted was 5%. RESULTS: The final study sample comprised 36 patients, 20 of whom were men. Of those 36 patients, 17 were submitted to lobectomy, 10 to pneumonectomy, 6 to segmentectomy, and 3 to bilobectomy. Chemotherapy was used in 15 patients, radiotherapy in 2, and a combination of radiotherapy and chemotherapy in 2. Improved quality of life was seen in the following domains: social (on postoperative day 90); physical/functional (some patients presenting better forced vital capacity and 6-minute walk test performance); and physical (in patients undergoing smaller resections). Lowered quality of life was seen in the following domains: social (for female patients); physical/social (resulting from radiotherapy, chemotherapy or both); and physical/functional (by postoperative day 30). CONCLUSIONS: It is important that studies evaluating the various determinants of quality of life, as well as the impact that cancer treatment modalities have on such variables, be conducted. The knowledge provided by such studies can contribute to improving the quality of life of patients undergoing pulmonary resection due to neoplasia. PMID- 17273562 TI - Early prognosis of acute asthma in the emergency room. AB - OBJECTIVE: To evaluate clinical and pulmonary function measurements taken in the first fifteen minutes of the assessment of acute asthma in the emergency room and used for prognostic purposes. METHODS: A prospective cohort study involving consecutive patients with acute asthma. Only patients who were between the ages of 12 and 55 and presented peak expiratory flow rates < or = 50% of predicted were included. Evaluations were performed upon admission, then again at 15 minutes and 4 hours after the initiation of treatment. Treatment included albuterol and ipratropium delivered by metered-dose inhaler with a spacer, together with 100 mg of intravenous hydrocortisone. Favorable outcomes were defined as peak expiratory flow > or = 50% of predicted after 4 hours of treatment, and unfavorable outcomes were defined as peak expiratory flow < 50% after 4 hours of treatment. RESULTS: Favorable outcomes were seen in 27 patients, and unfavorable outcomes were seen in 24 patients. In the multivariate analysis, peak expiratory flow as percentage of predicted was identified as the variable with the highest predictive value. A peak expiratory flow > or = 40% after 15 minutes of treatment showed significant power in predicting a favorable outcome (sensitivity = 0.74, specificity = 1.00, and positive predictive value = 1.00). A peak expiratory flow < 30% after 15 minutes of treatment was predictive of a poor outcome (sensitivity = 0.54, specificity = 0.93, and positive predictive value = 0.87). CONCLUSION: Our results suggest that measuring peak expiratory flow after 15 minutes of management in the emergency room is a useful tool for predicting outcomes in cases of acute asthma. PMID- 17273564 TI - Effects of pneumoperitoneum on the amplitude of diaphragmatic excursion in pigs. AB - OBJECTIVE: To study the effects that pneumoperitoneum achieved through carbon dioxide insufflation has on diaphragmatic excursion in pigs. METHODS: A total of 14 male Landrace pigs, 30 to 45 days of age and weighing five to seven kilograms each, were used. The sample was randomly and equally divided into two groups: one (n = 7) in which pneumoperitoneum was maintained at 10 mmHg for 60 minutes; and another (n = 7) in which pneumoperitoneum was maintained at 15 mmHg (also for 60 minutes). After anesthetic induction, the animals were intubated. Flow volume was monitored, and the amplitude of diaphragmatic excursion was analyzed using noninvasive ultrasound imaging of the right hemidiaphragm. RESULTS: In both groups, restricted diaphragmatic excursion was observed only during the procedure. There was no statistical difference between the two pressure levels studied. CONCLUSION: The amplitude of diaphragmatic excursion was restricted during abdominal insufflation, independent of the pressure level (within the 10 15 mmHg range), during the study period. PMID- 17273565 TI - Prevalence and characteristics of smoking among youth attending the University of Brasilia in Brazil. AB - OBJECTIVE: To determine the prevalence of smoking and to describe the profile and smoking habits of students attending the Universidade de Brasilia (University of Brasilia) in Brasilia, Brazil. METHODS: A total of 1341 students responded to a smoking questionnaire, adapted from the World Health Organization questionnaire, including questions directed at smokers, former smokers and nonsmokers. Twenty different courses in the areas of health, exact sciences and human sciences were evaluated. The students included in the study were duly enrolled in day courses and were evaluated during the second semester of 2003. RESULTS: The overall prevalence of smoking was 14.7%. Approximately 80.8% of the students were nonsmokers, and 4.5% were former smokers. In the study sample, 57.3% of the students were male. No significant difference (p > 0.05) in the prevalence of smoking was observed in terms of gender or class year. The mean age of the study population was 21.6 +/- 3.6 years, and the mean age at which the smoking habit was acquired was 17 +/- 2.8 years. The percentage of smokers was higher in the Geology, Communication, and History courses (32.9, 26.3 and 24.4%, respectively). Mean consumption was 7.5 cigarettes per day. The majority (72.6%) of the students used commercial cigarettes rather than other types of tobacco. CONCLUSION: The high prevalence of smoking observed in the present study is similar to that reported for other universities and indicates the need for smoking control policies in university environments. PMID- 17273566 TI - Availability and use of noninvasive ventilation in the intensive care units of public, private and teaching hospitals in the greater metropolitan area of Sao Paulo, Brazil. AB - OBJECTIVE: To determine the availability of noninvasive positive-pressure ventilation equipment, as well as the level of expertise and familiarity of physicians, nurses and physiotherapists with noninvasive positive-pressure ventilation in the intensive care units of public, private and teaching hospitals in the greater metropolitan area of Sao Paulo, Brazil. METHODS: On-site administration of questionnaires. RESULTS: Noninvasive positive-pressure ventilation equipment was widely available and was more commonly found in private hospitals than in teaching hospitals. Such equipment was least available in public hospitals, in which the predominant method was the use of mechanical ventilators designed for invasive ventilation and adapted to noninvasive positive pressure ventilation. In private hospitals, continuous flow ventilators were more common, whereas, in teaching hospitals, ventilators specifically designed for noninvasive ventilation were typically employed. All physiotherapists felt themselves capable of initiating noninvasive positive pressure ventilation, compared with 72.6% of physicians and 33.3% of nurses. Physicians and physiotherapists presented high percentages of correct answers when asked about the indications and contraindications for the use of noninvasive positive pressure ventilation. Over a one year period, more physiotherapists read articles about noninvasive positive-pressure ventilation and participated in related classes than did physicians, who in turn did so more than did nurses. CONCLUSION: Noninvasive positive-pressure ventilation equipment is widely available in the greater metropolitan area of Sao Paulo, although differences exist among public, private and teaching hospitals in terms of the type of equipment used. Physicians and physiotherapists exhibited considerable knowledge regarding the indications and contraindications for the use of noninvasive positive-pressure ventilation. More physiotherapists felt themselves able to initiate noninvasive positive pressure ventilation, and their knowledge of the subject was more current than was that of physicians or nurses. PMID- 17273567 TI - Incidence of acute lung injury and acute respiratory distress syndrome in the intensive care unit of a university hospital: a prospective study. AB - OBJECTIVE: To establish the incidence of acute lung injury and acute respiratory distress syndrome, as well as related risk factors and mortality in an intensive care unit. To compare patients developing lung injury with at-risk patients not presenting acute lung injury or acute respiratory distress syndrome. METHODS: The study was conducted in the intensive care unit of the Ribeirao Preto Hospital das Clinicas Emergency Room. All patients admitted between May 2001 and April 2002 were monitored prospectively. Clinical data, Acute Physiologic and Chronic Health Evaluation II score, complications, length of stay in the intensive care unit and lung injury data were recorded. RESULTS: Of the 524 patients admitted, 175 (33.4%) presented risk factors for acute lung injury and acute respiratory distress syndrome, 33 (6.3%) developed acute respiratory distress syndrome, and 12 (2.3%) developed acute lung injury. The main risk factors were pneumonia (37.7%), shock (32.0%), multiple trauma (24.6%) and sepsis (21.1%). Patients developing acute lung injury had higher Acute Physiologic and Chronic Health Evaluation II scores (p < 0.05), more frequently presented sepsis (p = 0.001), developed more complications (p = 0.001) and presented greater mortality (p = 0.001). The main cause of death was multiple organ failure (38.5%). CONCLUSION: The incidence of acute lung injury and acute respiratory distress syndrome was 2.3% and 6.3%, respectively. PMID- 17273568 TI - Functional profile of patients with tuberculosis sequelae in a university hospital. AB - OBJECTIVE: To describe data related to the pulmonary function of patients with sequelae of pulmonary tuberculosis, pleural tuberculosis or both. METHODS: In the outpatient clinic of a university hospital, 218 patients were evaluated. Of those 218, 56 had sequelae of tuberculosis (pulmonary, pleural or both), and 162 had other types of tuberculosis. All patients were evaluated in the pulmonary function laboratory between February 2000 and July 2004, and 43 were found to be eligible for inclusion in the study. Patients with a history of asthma, chronic pulmonary obstructive disease, cardiac insufficiency, collagen diseases, silicosis or thoracic surgery, as well as those for whom spirometry yielded unacceptable results or was not performed, were excluded. The lung fields were divided into six zones, and radiographic results were classified by degree: I (involvement of only one zone with no cavitation); II (involvement of two or three zones or of one zone with cavitation); or III (extensive involvement of three or more zones with or without cavitation). RESULTS: The final study sample comprised 50 patients, 44 (88%) of whom had pulmonary tuberculosis. The most prevalent form (17/50; 34%) was mixed ventilatory disturbance. Severe disturbances were more significant in degree III radiographs (p = 0.0002) and normal pulmonary function was predominant among patients presenting degree I and II radiographs (p = 0.002). CONCLUSION: The early discovery and treatment of tuberculosis contribute to reduce the number of cases, as well as the incidence of tuberculosis sequelae, thereby improving the quality of life of tuberculosis patients. Further studies, involving longitudinal, sequential analysis and larger samples of patients with tuberculosis sequelae, should be conducted in referral centers in Brazil. PMID- 17273569 TI - Prevalence of and factors related to tuberculosis in seropositive human immunodeficiency virus patients at a reference center for treatment of human immunodeficiency virus in the southern region of the state of Rio Grande do Sul, Brazil. AB - OBJECTIVE: In view of the relevance of co-infection with tuberculosis and human immunodeficiency virus, this study was designed to determine tuberculosis prevalence and identify factors related to tuberculosis in patients residing in a region in which both infections are highly prevalent. METHODS: All patients treated during 1999 at the HIV/AIDS Clinic of the Universidade Federal do Rio Grande (Rio Grande Federal University) University Hospital were evaluated retrospectively, from the time of human immunodeficiency virus diagnosis, in terms of the incidence of tuberculosis and its relationship to sociodemographic, behavioral and immunological factors. RESULTS: The sample included 204 patients, and tuberculosis prevalence was found to be 27%. The multivariate analysis showed a significant correlation between the development of tuberculosis and being of African descent (odds ratio: 4.76; 95% confidence interval: 1.93-11.72) and an inverse correlation between the development of tuberculosis and the TCD4+ lymphocyte count at the time of human immunodeficiency virus diagnosis (odds ratio: 0.995; 95% confidence interval: 0.993-0.997). When analyzed separately, other variables were found to be potential risk factors: being of the male gender (odds ratio: 2.49; 95% confidence interval: 1.15-5.39); and using illicit drugs (odds ratio: 2.1; 95% confidence interval: 1.02-4.31). CONCLUSION: The factors responsible for the development of tuberculosis among patients who are human immunodeficiency virus seropositive include immunological, socioeconomic and demographic factors. The high rate of tuberculosis prevalence among the seropositive patients underscores the urgent need to implement strategies that combine rapid identification and prompt treatment of individuals with active or latent infection, as well as of those with whom they have been in contact. PMID- 17273570 TI - Molecular markers in lung cancer: prognostic role and relationship to smoking. AB - Epidemiological studies have demonstrated a causal relationship between smoking and lung cancer. Although most lung cancer cases are linked to smoking, only a minority of heavy smokers develop lung cancer, leading to the notion that genetic factors affect individual susceptibility. The principal molecular changes in lung cancer are seen in tumor suppressor genes, proto-oncogenes, growth factors, telomerase activity, and methylation status of promoters. Well-known agents include angiogenesis-stimulating factors (such as vascular endothelial growth factor), as well as factors related to tumor cell proliferation and apoptosis (epidermal growth factor receptor, p53, K-ras, retinoblastoma and BCL-2). Several of these genetic factors have already been investigated, but no single parameter has yet presented sufficient selectivity regarding prognostic value or therapeutic efficacy. Treatment strategies to cure lung cancer should focus on these early genetic lesions in order to promote their repair or to eliminate these lung cancer cells. PMID- 17273571 TI - New treatments for chronic obstructive pulmonary disease using ergogenic aids. AB - Chronic obstructive pulmonary disease is currently considered a systemic disease, presenting structural and metabolic alterations that can lead to skeletal muscle dysfunction. This negatively affects the performance of respiratory and peripheral muscles, functional capacity, health-related quality of life and even survival. The decision to prescribe ergogenic aids for patients with chronic obstructive pulmonary disease is based on the fact that these drugs can avert or minimize catabolism and stimulate protein synthesis, thereby reducing the loss of muscle mass and increasing exercise tolerance. This review summarizes the available data regarding the use of anabolic steroids, creatine, L-carnitine, branched-chain amino acids and growth hormones in patients with chronic obstructive pulmonary disease. The advantage of using these ergogenic aids appears to lie in increasing lean muscle mass and inducing bioenergetic modifications. Within this context, most of the data collected deals with anabolic steroids. However, to date, the clinical benefits in terms of increased exercise tolerance and muscle strength, as well as in terms of the effect on morbidity and mortality, have not been consistently demonstrated. Dietary supplementation with substances of ergogenic potential might prove to be a valid adjuvant therapy for treating patients with advanced chronic obstructive pulmonary disease, especially those presenting loss of muscle mass or peripheral muscle weakness. PMID- 17273572 TI - Pulmonary blastoma: treatment through sleeve resection of the right upper lobe. AB - Pulmonary blastoma is a rare lung tumor that is composed of malignant epithelial and mesenchymal cells. It presents a pattern of rapid growth. Herein, we report the case of a patient with hemoptysis and a mass in the right upper lobe. The patient presented limited pulmonary function, and fiberoptic bronchoscopy revealed invasion of the intermediate bronchus. The patient underwent sleeve resection of right upper lobe, a technique never before described. After 36 months of follow-up, the patient remained asymptomatic. We also review the literature regarding treatment, clinical aspects and pathology. PMID- 17273573 TI - Sclerosing mediastinitis in the differential diagnosis of mediastinal tumors. AB - Sclerosing mediastinitis is a rare disorder characterized by an extensive fibrotic reaction involving the mediastinum. Due to the compression or invasion of mediastinal structures, the disorder mimics neoplasia. We present three cases of superior vena cava syndrome in which sclerosing mediastinitis was confirmed. The pathophysiological process is related to enlarged mediastinal lymph nodes, fibroblast proliferation and collagen deposition. The main causes of sclerosing mediastinitis are histoplasmosis and tuberculosis, both of which are prevalent in Brazil. It is difficult to make an accurate histopathological diagnosis using minimally invasive methods, and there is no effective treatment for this condition. In order to make a definitive diagnosis and resolve the aerodigestive tract obstruction, exploratory surgery is indicated. PMID- 17273574 TI - Pneumothorax and tension pneumopericardium following cardiothoracic surgery. AB - Herein, we report two cases of pneumothorax and tension pneumopericardium after cardiothoracic surgery. Both patients underwent pericardiotomy during the primary operation and developed pericardial tamponade as a complication. The treatment was tube thoracostomy, and both patients recovered completely. PMID- 17273575 TI - Obstructive sleep apnea: a contagious disease? PMID- 17273576 TI - Evaluating COPD from the perspective of the patient. PMID- 17273578 TI - Respiratory muscle evaluation in elective thoracotomies and laparotomies of the upper abdomen. AB - OBJECTIVE: To identify any possible relation between lower than predicted preoperative respiratory muscle function and the incidence of postoperative respiratory complications and death in elective thoracotomies and laparotomies of the upper abdomen. METHODS: A prospective cohort study was conducted, in which 70 patients over the age of 18 were monitored in two similar hospitals. In the preoperative evaluation performed at admission, patients were classified as presenting respiratory muscle function (as determined by measurement of maximal respiratory pressures) > 75% of the predicted value (n = 50) or < 75% of the predicted value (n = 20). Patients were monitored until discharge. In both groups, the incidence of pneumonia was determined, as was that of acute respiratory failure, bronchospasm, prolonged mechanical ventilation, atelectasis, pleural effusion, pneumothorax and death. A comparative analysis was made between the groups, and relative risk was calculated. RESULTS: In the study sample, the overall incidence of postoperative complications was 22.86% (16/70): 55% (11/20) in the group of patients presenting < 75% of the predicted value; and 10% (5/50) in the group of patients presenting > 75% of the predicted value. Patients in the < 75% of the predicted value group presented a relative risk of 5.5 (95% confidence interval between 2.19 and 13.82). CONCLUSION: Respiratory muscle function below the predicted value was found to be related with higher relative risk of postoperative complications in the surgical procedures studied. PMID- 17273577 TI - Using the forced oscillation technique to evaluate bronchodilator response in healthy volunteers and in asthma patients presenting a verified positive response. AB - OBJECTIVE: To use the forced oscillation technique to evaluate asthma patients presenting positive bronchodilator responses (confirmed through spirometry) and compare the results with those obtained in healthy individuals. METHODS: The study sample consisted of 53 non-smoking volunteers: 24 healthy subjects with no history of pulmonary disease and 29 asthmatics presenting positive bronchodilator response, as determined through analysis of spirometry findings. All of the subjects were submitted to forced oscillation technique and spirometry immediately before and 20 minutes after the administration of salbutamol spray (300 g). The parameters derived from the forced oscillation technique were total respiratory resistance, total respiratory reactance, resistance extrapolated to the y axis, the slope of resistance, and dynamic compliance. The parameters measured in the spirometry evaluation tests were forced expiratory volume in one second and forced vital capacity. RESULTS: In the control group, bronchodilator use produced a significant alteration in the resistance extrapolated to the y axis (p < 0.001), although no significant differences were observed in the slope of resistance or in dynamic compliance. Analysis of the asthma patients revealed significant differences between the prebronchodilator and postbronchodilator values for all spirometry and forced oscillation technique parameters. Values of p < 0.001 were obtained for all comparisons between the two groups. CONCLUSION: The modifications provoked by use of the forced oscillation technique were in direct concordance with the pathophysiology of the bronchodilator response in asthma patients, indicating that the forced oscillation technique could be useful as a complement to spirometry in these patients. PMID- 17273579 TI - Evaluating physical capacity in patients with chronic obstructive pulmonary disease: comparing the shuttle walk test with the encouraged 6-minute walk test. AB - OBJECTIVE: To evaluate the applicability of the incremental (shuttle) walk test in patients with chronic obstructive pulmonary disease and compare the performance of those patients on the shuttle walk test to that of the same patients on the encouraged 6-minute walk test. METHODS: A cross-sectional study was conducted, in which 24 patients with chronic obstructive pulmonary disease were selected. In random order, patients were, after an initial practice period, submitted to a shuttle walk test and an encouraged 6-minute walk test. RESULTS: The patients obtained a higher heart rate (expressed as a percentage of that predicted based on gender and age) on the encouraged 6-minute walk test (84.1 +/- 11.4%) than on the shuttle walk test (76.4 +/- 9.7%) (p = 0.003). The post-test sensation of dyspnea (Borg scale) was also higher on the encouraged 6-minute walk test. On average, the patients walked 307.0 +/- 89.3 meters on the shuttle walk test and 515.5 +/- 102.3 meters on the encouraged 6-minute walk test (p < 0.001). There was a good correlation between the two tests in terms of the distance walked (r = 0.80, p < 0.001). CONCLUSION: The shuttle walk test is simple and easy to implement in patients with chronic obstructive pulmonary disease. The encouraged 6-minute walk test produced higher post-test heart rate and greater post-test sensation of dyspnea than did the shuttle walk test. PMID- 17273580 TI - Using the Saint George's Respiratory Questionnaire to evaluate quality of life in patients with chronic obstructive pulmonary disease: validating a new version for use in Brazil. AB - OBJECTIVE: The objective of this study was to evaluate the applicability of a modified version of the Saint George's Respiratory Questionnaire. The version evaluated elicits "agree" and "do not agree", rather than "yes" and "no", responses. The intention is to facilitate the comprehension of double-negative questions and to promote better recollection of symptoms by patients by shortening their symptom histories from 12 months to 3 months. METHODS: A total of 30 clinically stable patients with chronic obstructive pulmonary disease were evaluated. The Saint George's Respiratory Questionnaire and the modified version of the same were administered 15 days apart. RESULTS: All of the patients presented health-related alterations in their quality of life. Comparing mean scores between the two questionnaires, the greatest difference was seen in the Symptoms domain. No significant differences were found in any of the remaining domains or in the total scores. In a subsequent analysis, significant correlations between the two questionnaires were found in all domains: Symptoms (r = 0.71; p < 0.001); Activity (r = 0.75; p < 0.001); Impact (r = 0.73; p < 0.001) and Total (r = 0.86; p < 0.001). CONCLUSION: The modified version of the Saint George's Respiratory Questionnaire is as effective as the original in gauging quality of life. However, various symptoms recollection time frames should be investigated in order to determine which would be the best time frame to employ in the analysis. PMID- 17273581 TI - Influence of the technique of re-educating thoracic and abdominal muscles on respiratory muscle strength in patients with cystic fibrosis. AB - OBJECTIVE: To determine the effect that re-education of the thoracic and abdominal muscles has on the respiratory muscle strength of patients with cystic fibrosis evaluated over time at the Cystic Fibrosis Outpatient Clinic of the Universidade Catolica de Brasilia (Catholic University of Brasilia). METHODS: The sample consisted of 29 cystic fibrosis patients, characterized based on anthropometric, genetic and bacterial colonization data. The patients were submitted to physical therapy sessions, involving re-education of the respiratory muscles, twice a week for four months. Spirometry, pressure manometry and anthropometry were performed before and after each session. RESULTS: Comparing baselines values to those obtained after physical therapy, increases in maximum inspiratory pressure and maximum expiratory pressure were observed in all patients, those without any obstructive respiratory disease and those with mild obstructive respiratory disease (p < 0.05). A positive correlation between age and maximum expiratory pressure was observed for most of the patients. Maximum inspiratory pressure correlated positively with age only in the group with mild obstructive respiratory disease (p = 0.012; r = 0.817). In female patients and in the group of patients without obstructive respiratory disease, a negative correlation was observed between maximum expiratory pressure and colonization with Pseudomonas aeruginosa (p = 0.036; r = -0.585). CONCLUSION: Use of the thoracic and abdominal muscle re-education technique increased respiratory muscle strength in the cystic fibrosis patients studied, a finding that underscores the importance of including physical therapy in the treatment of these patients. PMID- 17273582 TI - Yoga versus aerobic activity: effects on spirometry results and maximal inspiratory pressure. AB - OBJECTIVE: To clarify whether, in healthy individuals, practicing yoga can modify maximal inspiratory pressure and spirometric indices when compared with the practice of aerobic exercise. MEYHODS: A controlled clinical trial. A total of 31 healthy volunteers were allocated to practice aerobic exercise (n = 15) or to practice yoga (n = 16). Those in the first group served as controls and engaged in aerobic exercise for 45-60 minutes, twice a week for three months. Those in the second group practiced selected yogic techniques, also in sessions of 45-60 minutes, twice a week for three months. Forced vital capacity, forced expiratory volume in one second and maximal inspiratory pressure were measured before and after the three months of training. RESULTS: No significant alterations were seen in the spirometric indices. A slight, although not significant, improvement in maximal inspiratory pressure was seen in both groups. However, there was a significant difference, seen in both genders, between the absolute delta (final value minus baseline value) of maximal inspiratory pressure for the group practicing yoga and that obtained for the group engaging in aerobic exercise (males: 19.5 cm H2O versus 2.8 cm H2O, p = 0.05; females: 20 cm H2O versus 3.9 cm H2O, p = 0.01). CONCLUSION: Neither yoga nor aerobic exercise provided a statistically significant improvement in maximal inspiratory pressure after three months. However, the absolute variation in maximal inspiratory pressure was greater among those practicing yoga. PMID- 17273583 TI - Lung abscess: analysis of 252 consecutive cases diagnosed between 1968 and 2004. AB - OBJECTIVE: To relate the experience of the staff at a health care facility specializing in the management of patients with aspiration lung abscess. METHODS: Diagnostic aspects and therapeutic results of 252 consecutive cases of lung abscess seen in patients hospitalized between 1968 and 2004. RESULTS: Of the 252 patients, 209 were male, and 43 were female. The mean age was 41.4 years, and 70.2% were alcoholic. Cough, expectoration, fever and overall poor health were seen over 97% of patients. Chest pain was reported by 64%, 30.2% presented digital clubbing, 82.5% had dental disease, 78.6% reported having lost consciousness at least once, and 67.5% presented foul smelling sputum. In 85.3% of the patients, the lung lesions were located either in the posterior segments of the upper lobe or in the superior segments of the lower lobe, and 96.8% were unilateral. Concomitant pleural empyema was seen in 24 (9.5%) of the patients. Mixed flora was identified in the bronchopulmonary or pleural secretions of 182 patients (72.2%). All patients were initially treated with antibiotics (mainly penicillin or clindamycin), and postural drainage was performed in 98.4% of cases. Surgical procedures were performed in 52 (20.6%) of the patients (drainage of empyema in 24, pulmonary resection in 22 and drainage of the abscess in 6). Cure was obtained in 242 patients (96.0%), and 10 (4.0%) died. CONCLUSION: Lung abscess occurred predominantly in male adults presenting dental disease and having a history of loss of consciousness (especially as a result of alcohol abuse). Most of the patients were treated clinically with antibiotics and postural drainage, although some surgical procedure was required in one-fifth of the study sample. PMID- 17273584 TI - Prevalence of risk factors for obstructive sleep apnea syndrome in interstate bus drivers. AB - OBJECTIVE: To determine the prevalence of risk factors for obstructive sleep apnea syndrome in interstate bus drivers. METHODS: This study involved 262 professional interstate bus drivers employed by a Brazilian company headquartered in the Federal District. The drivers were evaluated using a questionnaire designed to assess respiratory sleep disorders, the Epworth Sleepiness Scale, test of sustained attention, test of divided attention and anthropometric measurements. RESULTS: Body weight was found to be above the ideal in 68% of the drivers evaluated, 34% of which had a neck circumference = 42 cm. During the study period, the drivers reported using tobacco (27%), cola-based soft drinks (55%), alcohol (65%) and coffee (88%). The Epworth Sleepiness Scale score was = 10 points in 28%. Snoring was reported by 36%, sleep apnea by 5%, a sensation of suffocation during sleep by 12%, restless sleep by 29% and drowsiness while driving by 48%. There were 42% who had been involved in transit accidents, 7.6% of which were attributed to hypersomnolence. Those scoring higher than 10 of the Epworth Sleepiness Scale presented lower levels of sustained attention. In addition, a reduction in divided attention was found to correlate with greater daytime sleepiness and larger neck circumference. CONCLUSION: The rate of stimulant use found in the group of drivers evaluated is alarming. The high prevalence of daytime sleepiness indicates that attentiveness is reduced in this population. PMID- 17273585 TI - Extraesophageal manifestations of gastroesophageal reflux disease. AB - Gastroesophageal reflux disease often presents as heartburn and acid reflux, the so-called "typical" symptoms. However, a subgroup of patients presents a collection of signs and symptoms that are not directly related to esophageal damage. These are known collectively as the extraesophageal manifestations of gastroesophageal reflux disease. Principal among such manifestations are bronchospasm, chronic cough and laryngitis, which are classified as atypical symptoms. These manifestations comprise a heterogeneous group. However, some generalizations can be made regarding all of the subgroups. First, although the correlation between gastroesophageal reflux disease and the extraesophageal manifestations has been well established, a cause-and-effect relationship has yet to be definitively elucidated. In addition, the main proposed pathogenic mechanisms of extraesophageal reflux are direct injury of the extraesophageal tissue (caused by contact with gastric acid) and the esophagobronchial reflex, which is mediated by the vagus nerve. Furthermore, gastroesophageal reflux disease might not be considered in the differential diagnosis of patients presenting only the atypical symptoms. In this article, we review the extraesophageal manifestations of gastroesophageal reflux disease, discussing its epidemiology, pathogenesis, diagnosis and treatment. We focus on the most extensively studied and well-established presentations. PMID- 17273586 TI - Systemic manifestations in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease is progressive and is characterized by abnormal inflammation of the lungs in response to inhalation of noxious particles or toxic gases, especially cigarette smoke. Although this infirmity primarily affects the lungs, diverse extrapulmonary manifestations have been described. The likely mechanisms involved in the local and systemic inflammation seen in this disease include an increase in the number of inflammatory cells (resulting in abnormal production of inflammatory cytokines) and an imbalance between the formation of reactive oxygen species and antioxidant capacity (leading to oxidative stress). Weakened physical condition secondary to airflow limitation can also lead to the development of altered muscle function. Chronic obstructive pulmonary disease presents diverse systemic effects including nutritional depletion and musculoskeletal dysfunction (causing a reduction in exercise tolerance), as well as other effects related to the comorbidities generally observed in these patients. These manifestations have been correlated with survival and overall health status in chronic obstructive pulmonary disease patients. In view of these facts, the aim of this review was to discuss findings in the literature related to the systemic manifestations of chronic obstructive pulmonary disease, emphasizing the role played by systemic inflammation and evaluating various therapeutic strategies. PMID- 17273587 TI - Resection of a mediastinal schwannoma using video-assisted thoracoscopy. AB - Schwannomas are tumors that are typically benign. They are derived from Schwann cells (glial cells of the peripheral nervous system that serve to separate and isolate nerve cells from adjacent structures). The most common type of schwannoma is a benign tumor of cranial nerve VIII and is referred to as an acoustic neuroma. When extradural, such tumors usually present as masses that can invade adjacent structures, thereby becoming symptomatic, as in the case of intrathoracic schwannomas (typically found in the posterior mediastinum). Herein, we present a case of a schwannoma treated through video-assisted thoracoscopy, and we review the literature on the subject. PMID- 17273588 TI - Claude Bernard-Horner syndrome resulting from pleural empyema. AB - Claude Bernard-Horner syndrome presents various etiologies and occurs as the direct result of interrupted nerve signaling at any point along the nerve trajectory, be it intrathoracic or extrathoracic. Herein, we report a case of Claude Bernard-Horner syndrome caused by loculated pleural empyema located in the paravertebral region of the upper third of the right hemithorax. The patient was submitted to thoracotomy in order to drain the infected fluids. The end result was satisfactory, including resolution of the infection, pulmonary expansion, and remission of the syndrome. PMID- 17273589 TI - Mounier-Kuhn syndrome. AB - Mounier-Kuhn syndrome, or tracheobronchomegaly, is a rare clinical entity characterized by abnormal dilation of the trachea and main bronchi. The diagnosis can usually be made by measuring the tracheal diameter. We report the case of a 40-year-old black man with refractory lower respiratory tract infection. Tracheobronchomegaly was confirmed through computed tomography. PMID- 17273591 TI - [Epidemiological surveillance and occupational respiratory diseases]. AB - For every communicable disease, the construction of a database is fundamental to prioritizing related measures (educational, prevention and control), as well as to the development of public health policies. Although various countries possess reliable systems of epidemiological surveillance, Brazil still lacks an adequate structure for the collection, processing and dissemination of data. We consider it imperative that the health professionals working in this area make a unified effort, as soon as possible, to compile a database that suitably addresses the epidemiology of occupational respiratory diseases. PMID- 17273592 TI - [Work history]. AB - Just as a complete patient history is fundamental to making any diagnosis, the history of environmental exposure in the workplace forms the informational base needed in order to understand occupational respiratory diseases. It is estimated that 20% of all cases of interstitial or airway disease are related to such exposure. However, information regarding potential environmental exposure is rarely included in the patient history, nor is job/occupation/function taken into consideration. Therefore, this theme has become pivotal to the discussion among health care professionals working in this area, who must decide whether evaluating and estimating the magnitude of this problem are truly desirable goals. PMID- 17273594 TI - [Diseases of the upper respiratory tract]. AB - A great number of agents found in inhaled air, whether in the environment or in the workplace, can cause symptoms and diseases of the upper respiratory tract. Unfortunately, establishing the cause-and-effect relationship between exposure to one of the various types of agents that can provoke such diseases and the diseases themselves is not routine practice among the health professionals involved. A comprehensive list of these agents and their relationships with the effects and onset of such illnesses is available in the literature. Chief among these ills are rhinosinusitis, dysphonia and ulceration/perforation of the nasal septum, as well as tumors in the nasal cavity or paranasal sinuses, all of which can be work related. Although widely available, diagnostic procedures for the investigation of occupational etiology are not yet routinely employed. In general, early identification of, and discontinuation of the contact with, the causal agent can resolve the problem, thereby averting the development of the chronic form of the disease. As with other types of occupational respiratory diseases, prevention and control programs are indispensable in the fight against these illnesses. PMID- 17273595 TI - [Occupational asthma]. AB - Work-related asthma is one of the principal occupational respiratory diseases in terms of prevalence. Innumerable chemical substances used in various production processes can cause or aggravate occupational asthma. This chapter contains a brief description of the definition and classification of work-related asthma, as well as the epidemiological repercussions, natural course, diagnostic criteria, progression and legal aspects of the disease, with the objective of raising an alert regarding this disease and its implications for workers. PMID- 17273596 TI - [Occupational chronic obstructive pulmonary disease]. AB - Occupational chronic obstructive pulmonary disease, despite having been widely discussed for nearly half a century, is still rarely addressed in Brazil. Various studies, especially those that were population-based, have revealed the relationship between occupational exposure to aerosols and impairment of the airways. This chapter aims to remind physicians of the diagnosis of occupational chronic obstructive pulmonary disease by presenting a succinct review of the literature on the theme, which should be incorporated into the Global Initiative for Chronic Obstructive Lung Disease, in terms of the scope of the diagnostic basis as well as in terms of the questionnaire specific for the disease. Collecting detailed work histories and characterizing exposure to inhaled agents known to have deleterious effects on the respiratory system will surely result in improved approaches to making diagnoses and prognoses of this disease, as well as contributing to its greater control. PMID- 17273597 TI - [Silicosis]. AB - This chapter presents a review of the national and international literature on the subject of silicosis. Epidemiological, pathological, diagnostic and pulmonary function aspects are discussed. The clinical classification and methods of treating silicosis are reviewed, as are other silicarelated diseases such as tuberculosis, lung cancer and scleroderma. Prevention and medical-legal aspects are also discussed. PMID- 17273598 TI - [Asbestos-related diseases]. AB - This chapter presents a bibliographic review of asbestos-related diseases. The latest diagnostic, radiological, computed tomography and lung function aspects of benign pleural disease, asbestosis, occupational lung cancer and mesothelioma are discussed. PMID- 17273600 TI - [Other pneumoconioses]. AB - The most prevalent pneumoconioses are silicosis, asbestosis and coal worker's pneumoconiosis. Other pneumoconioses that have distinct clinical, functional and structural repercussions are caused by inhalation of metal powder in fumes from metals or organic salts. The distinction in terms of the chemical form of the inhaled compound is related to the tissue reaction and to the prognosis. Simple pneumoconiosis, siderosis, berylliosis and phosphate rock-related pneumoconiosis, as well as chronic obstructive pulmonary disease caused by exposure to heavy metals, are succinctly discussed. As an instrument of etiologic investigation of these pneumoconioses, the taking of occupational histories is essential. PMID- 17273599 TI - [Clinical repercussions of exposure to atmospheric pollution]. AB - Atmospheric pollution is a topic of extensive discussion the world over. The clinical repercussions of exposure to the principal atmospheric pollutants are summarized herein. According to the American Environmental Protection Agency, air quality standards for these agents are set based on their primary and half-life values. The respiratory effects of the burning of fossil fuels and biomass are succinctly presented, with a special focus on alerting health care professionals of the increased morbidity related to environmental pollution. PMID- 17273601 TI - [Occupational lung cancer]. AB - The objective of this chapter was to review the occupational risk factors for developing lung cancer. Initially, the significance of lung cancer in the Brazilian population is addressed. Subsequently, the relationships between the genesis of this type of neoplasia and various physical and chemical agents generated by industrial processes are discussed. In the conclusion, the roles that clinical diagnosis and early prevention play in controlling occupational lung cancer are addressed. PMID- 17273602 TI - [Granulomatous diseases of occupational etiology]. AB - A variety of diseases are encompassed in the didactic denomination of "granulomatous diseases of probable occupational etiology". As well as presenting similar clinical aspects, such diseases are characterized by certain common traits: formation of granulomas; systemic and respiratory manifestations; environmental or occupational exposure to organic or inorganic agents; and T lymphocyte involvement in the pathogenesis. Included in this category are hypersensitivity pneumonitis, mycobacteriosis (all forms) and sarcoidosis, as well as beryllium disease and other lung diseases caused by exposure to heavy metals. In order to highlight the risk of developing one of these diseases as a result of environmental or occupational exposure to etiologic agents, we address aspects related to epidemiology, pathogenesis and evaluation of exposure of these diseases, as well as those related to diagnostic criteria, prevention and control. We have given special emphasis to groups of individuals considered to be at high risk for developing these diseases, as well as to the need for health care professionals to remain aware of the potential occupational etiology of such diseases, a decisive factor in devising effective measures of prevention and epidemiological surveillance. PMID- 17273603 TI - [Imaging in occupational lung diseases]. AB - This chapter consists of a review of the literature regarding radiographic and tomographic characteristics of the principal occupational respiratory diseases (silicosis and asbestosis). Special attention is given to the practical relevance of high-resolution computed tomography, which is the most sensitive and specific method of identifying and quantifying the extent of pleural and parenchymal lesions related to such diseases. PMID- 17273604 TI - [Evaluation of respiratory dysfunction and disability]. AB - The determination of functional consequences (dysfunction) and their impact on daily life (incapacitation) is central to the evaluation of patients with occupational respiratory diseases. The present review addresses the fundamentals underlying the instruments used to determine the degree of dysfunction, including clinical aspects, as well as those related to pulmonary function and, in some circumstances, exercise tolerance. In particular, a multifactorial system of classifying the degree of dysfunction is presented, with the objective of informing decisions related to the awarding of retirement benefits in Brazil. PMID- 17273605 TI - [Histopathological diagnosis of pneumoconiosis]. AB - Asbestos-related diseases constitute a major health problem due to the great number of workers exposed to asbestos over the past 50 years. Personal injury lawsuits against industries that deal with asbestos number in the hundreds, and new cases continue to be filed. The scientific issues related to asbestos are complex, and, although the broad outlines of asbestos-related diseases have been well-established, many significant aspects (such as the pathology involved) are poorly understood. In Brazil, asbestos has been mined commercially since 1940, with production levels recently approaching 200,000 tons/year, resulting in the asbestos exposure of approximately 10,000 workers in the mining activity, and an unknown number of workers in asbestos-cement industry, primarily roofers and concrete rooftop water tank installers. One study, using appropriate methods of scientific investigation to evaluate the effects of such exposure on the health of asbestos mine workers in Brazil was conducted as part of a multicenter study and entitled "Morbidity and Mortality Among Workers Exposed to Asbestos in Mining Activities, 1940-1996". Drawing upon the experience acquired during the course of that study, the objective of the current report was to give an overview of asbestos-related diseases, with a special focus on the difficulties involved in establishing the histopathological diagnosis. PMID- 17273606 TI - Compliance with environmental control measures in the homes of children and adolescents with asthma. AB - OBJECTIVE: To determine, through home visits, the rate of compliance with environmental control measures in the homes of children with asthma. METHODS: This study involved 98 asthma patients between the ages of 4 and 15. The parents of those children and adolescents received instruction in how to carry out environmental control measures and were encouraged to perform such measures continuously for a period of 90 days. Home visits, which included direct inspection of the domicile and administration of a questionnaire, were made before and after this 90-day period. In cases of noncompliance, parents were asked to explain why they did not carry out the control measures. Statistical analysis was performed using the McNemar test. RESULTS: Overall compliance with the various items studied was 11.1%, ranging from -4.1% (for curtain control, p = 0.63) to 22.6% (for stuffed toys, p < 0.001). Passive smoking was reduced to 9.7% (p = 0.02). Among the families studied, the mean monthly income was 2.5 times the national minimum wage. When asked why they had not adopted the recommended measures, noncompliant parents gave, among others, the following explanations: "economic hardship" (60.1%); "the measures were too difficult to carry out" (6.1%); "nonparticipation of the father" (4%); and "lack of time on the part of the mother" (4%). CONCLUSION: Environmental control measures were carried out sporadically, possibly reflecting the influence of socioeconomic and cultural factors. PMID- 17273607 TI - Bronchial hyperresponsiveness to hypertonic saline challenge in children and adolescents. AB - OBJECTIVE: To assess airway hyperresponsiveness to 4.5% hypertonic saline solution in comparison to that obtained through challenge with other bronchoconstriction agents and in relation to patient allergic sensitization. METHODS: A cross-sectional, experimental study was conducted, initially involving 85 subjects. After exclusions, the final sample consisted of 62 patients, divided into two groups: a study group of those with asthma (n = 45) and a control group of those with no asthma or allergies (n = 17). Hypertonic saline was nebulized using an ultrasonic nebulizer and administered successively for 0.5, 1, 2, 4 and 8 minutes until a drop in forced expiratory volume in one second of = 15% was achieved in relation to the baseline value. The level of specific immunoglobulin E to Dermatophagoides pteronyssinus level was determined by ImmunoCAP assay and was considered positive when > 0.35 kU/L. RESULTS: In the 36 asthma group subjects presenting a response, the mean drop in forced expiratory volume in one second after hypertonic saline nebulization was 27.4%. None of control group subjects (immunoglobulin E < 0.35 kU/L) presented a positive response to hypertonic saline. The mean forced expiratory volume in one second for control group subjects was 9%. The results of a bronchial provocation test were negative in 9 of the asthma group subjects. The frequency of bronchial provocation test positivity was higher in the subjects presenting elevated levels of specific immunoglobulin E, indicating that there is a relationship between bronchial hyperresponsiveness and the level of specific immunoglobulin E. The sensitivity and specificity of the test were 80% and 92%, respectively. CONCLUSION: Bronchial provocation with hypertonic saline presents satisfactory sensitivity and specificity. Therefore, in addition to being a low cost procedure that requires very little equipment, it is a useful means of assessing hyperresponsiveness in children and adolescents. PMID- 17273608 TI - Efficacy of inhaled formoterol in reversing bronchoconstriction. AB - OBJECTIVE: To evaluate the effectiveness and onset of action of formoterol delivered by dry-powder inhaler in reversing methacholine-induced bronchoconstriction. METHODS: Patients presenting a drop in forced expiratory volume in one second > 20% after methacholine inhalation were included. A total of 84 patients were evaluated. All of the participating patients presented respiratory symptoms of unknown origin, which were being investigated. The patients were randomized to receive 200 microg of spray fenoterol (n = 41) or 12 microg of dry-powder inhaler formoterol (n = 43), both administered in order to achieve immediate reversal of methacholine-induced bronchoconstriction. We evaluated the decrease in forced expiratory volume in one second (in relation to the baseline value) after methacholine challenge and the dose of methacholine required to provoke a drop of 20% in forced expiratory volume in one second, as well as the increase in forced expiratory volume in one second (in relation to the baseline value) at five and ten minutes after bronchodilator use. RESULTS: There were no significant differences related to gender, age, weight, height or dose of methacholine required to provoke a drop of 20% in forced expiratory volume in one second. Nor were there any significant differences in terms of baseline or post-methacholine forced expiratory volume in one second. In the fenoterol group, the mean postbronchodilator increase in forced expiratory volume in one second increase was 34% (at five minutes) and 50.1% (at ten minutes), compared with 46.5% (at five minutes) and 53.2% (at ten minutes) in the formoterol group. CONCLUSION: The bronchodilator effect of formoterol at five and ten minutes after methacholine-induced bronchoconstriction was similar to that of fenoterol. Despite being a long-acting bronchodilator, formoterol also has a rapid onset of action, which suggests that it could be employed as a relief medication in cases of bronchoconstriction occurring during asthma attacks. PMID- 17273609 TI - Nocturnal desaturation: predictors and the effect on sleep patterns in patients with chronic obstructive pulmonary disease and concomitant mild daytime hypoxemia. AB - OBJECTIVE: To determine the nocturnal oximetry pattern in chronic obstructive pulmonary disease patients having no sleep apnea and presenting mild daytime hypoxemia, to identify probable daytime parameters capable of predicting nocturnal desaturation, and to evaluate the influence of nocturnal desaturation on the sleep pattern of these patients. METHODS: Twenty-five patients were divided into two groups: those with nocturnal desaturation and those without. RESULTS: Comparing the first group (52%) with the second, we found the following: age, 63 +/- 5 years versus 63 +/- 6 years; forced expiratory volume in the first second = 53 +/- 31% versus 56 +/- 19% predicted; ratio of forced expiratory volume in the first second to forced vital capacity, 49 +/- 14% versus 52 +/- 10%; arterial oxygen tension, 68 +/- 8 mmHg versus 72 + 68 mmHg; and arterial oxygen saturation, 93 +/- 2% versus 94 +/- 1%. Patients in the nocturnal desaturation group presented lower daytime arterial oxygen saturation and nocturnal arterial oxygen saturation by pulse oximetry. There was no difference between the two groups in terms of the sleep patterns observed. The ratio of forced expiratory volume in the first second to forced vital capacity was found to correlate with forced vital capacity, daytime arterial oxygen tension and daytime arterial oxygen saturation. In addition, arterial oxygen saturation by pulse oximetry during exercise was found to correlate with nocturnal arterial oxygen saturation by pulse oximetry. However, only daytime arterial oxygen saturation was predictive of nocturnal desaturation. CONCLUSION: The only variable capable of predicting nocturnal desaturation was daytime arterial oxygen saturation. Nocturnal desaturation did not influence the sleep patterns of patients with chronic obstructive pulmonary disease accompanied by mild daytime hypoxemia. PMID- 17273610 TI - Using the forced oscillation technique to evaluate respiratory resistance in individuals with silicosis. AB - OBJECTIVE: To evaluate the resistance values obtained through the use of the forced oscillation technique in patients with varying degrees of airway obstruction resulting from silicosis. METHODS: A total of 40 never-smoking volunteers were analyzed: 10 were healthy subjects with no history of pulmonary disease or silica exposure, and 30 had silicosis. The forced oscillation technique was used to examine the subjects, and spirometry was used as a reference in order to classify the obstruction by degree. This classification resulted in five groups: control (n = 10); normal exam, composed of individuals diagnosed clinically and radiologically with silicosis but presenting normal spirometry results (n = 7); mild obstruction (n = 10); moderate obstruction (n = 8); and severe obstruction (n = 5). RESULTS: The reduction observed in the spirometric values corresponded to a significant increase in the total respiratory resistance (p < 0.001), as well as in airway resistance (p < 0.003). A significant reduction in ventilation homogeneity was also observed (p < 0.004). CONCLUSION: In individuals with silicosis, the additional respiratory resistance related data obtained through the use of the forced oscillation technique can complement spirometric data. Therefore, the forced oscillation technique presents great potential for the analysis of such patients. PMID- 17273611 TI - Early diagnosis of lung cancer: the great challenge. Epidemiological variables, clinical variables, staging and treatment. AB - OBJECTIVE: To evaluate confirmed cases of lung cancer, reviewing epidemiological variables, clinical variables, staging and treatment. METHODS: The cases of 263 patients were studied. All of the patients had been treated at the Universidade Federal do Parana (Federal University of Parana) Hospital de Clinicas or at the Hospital Erasto Gaertner, two institutions that, together, serve a significant portion of the patients seeking treatment in the city of Curitiba, located in the state of Parana. This was a retrospective study, involving the administration of questionnaires. The descriptive analysis of the data obtained was performed using the Epi-Info program. RESULTS: There was a predominance of male patients (76%). At the time of diagnosis, the majority of patients (90%) were smokers or former smokers. In 87% of the cases, there was no history of lung disease. The most common initial symptoms were cough (142 cases) and chest pain (92 cases). Non small cell lung cancer was found in 87% of the patients, and the most common histological type was spinocellular carcinoma, which was found in 49% of all of the patients. Smoking was found to be the most significant predisposing factor. CONCLUSION: The characteristics of lung cancer progression, such as the nonspecificity of the initial symptoms, the duration of tumor growth and the course of the tumor, together with the lack of tracking programs, are the principal factors that hinder the early detection of lung cancer, making it difficult to treat lung cancer patients and to increase their survival. PMID- 17273612 TI - Radiographic alterations in patients presenting human immunodeficiency virus/tuberculosis coinfection: correlation with CD4+ T cell counts. AB - OBJECTIVE: To look for correlations between radiological patterns and CD4+ T cell counts in patients coinfected with tuberculosis and human immunodeficiency virus. METHODS: Patients included were selected from among those presenting human immunodeficiency virus/tuberculosis coinfection and admitted to the Nereu Ramos Hospital, located in Florianopolis, Brazil, between January of 2000 and December of 2003. RESULTS: A total of 87 patients were included. The mean age was 34 +/- 8 years, and 6.8% were non-Caucasian. The mean CD4+ T cell count was 220.2 cells/mm(3) (median, 144 cells/mm(3)), and 56.4% of the patients presented less than 200 cells/mm(3). We identified the following radiographic patterns and related them to the CD4+ T cell counts: the alveolar pattern in 50.6% of the cases (56.8% CD4+ T cells < 200); the interstitial pattern in 32.2% (53.6% CD4+ T cells < 200); pleural effusion in 24.1% (47.6% CD4+ T cells < 200); cavitation in 24.1% (57.1% CD4+ T cells < 200); enlarged mediastinal or hilar lymph nodes in 11.5% (90% CD4+ T cells < 200); and a normal pattern in 11.5% (60% CD4+ T cells < 200). The mean CD4+ T cell counts for the radiologic patterns isolated were as follows: 235.2/mm(3) (alveolar consolidation); 208.8/mm(3) (interstitial); 243.3/mm(3) (pleural effusion); 265/mm(3) (cavitation); 115.1/mm(3) (enlarged mediastinal or hilar lymph nodes) (p < 0.05); and 205.5/mm(3) (presenting no radiological alterations). As noted, mediastinal/hilar lymph node enlargement was the only pattern that correlated with the degree of cell-mediated immunity in a statistically significant way. CONCLUSION: With the exception of mediastinal/hilar lymph node enlargement, the radiographic patterns were randomly distributed in relation to the CD4+ T cell counts. PMID- 17273613 TI - Evaluation of polymerase chain reaction in the diagnosis of pulmonary tuberculosis in indigenous and non-indigenous patients. AB - OBJECTIVE: To evaluate the accuracy of bacteriological methods and of polymerase chain reaction (with primers specific for IS6110 of the Mycobacterium tuberculosis complex) in testing sputum samples from indigenous (Amerindian) and non-indigenous patients. METHODS: A total of 214 sputum samples (154 from indigenous patients and 60 from non-indigenous patients) were analyzed in order to determine the accuracy of smear microscopy (direct and concentrated versions) for acid-fast bacilli, culture, and polymerase chain reaction. RESULTS: Both microscopy methods presented low sensitivity in comparison with culture and polymerase chain reaction. Specificity ranged from 91% to 100%, the concentrated acid-fast smear technique being the least specific. Nontuberculous mycobacteria were isolated three times more frequently in samples from indigenous patients than in those from non-indigenous patients. False-positive and false-negative polymerase chain reaction results were more common in the indigenous population. CONCLUSION: Positivity and isolation of nontuberculous mycobacteria in the acid fast smear in conjunction with polymerase chain reaction positivity raise the following hypotheses: nontuberculous mycobacteria species with DNA regions homologous to, or even still possessing, the M. tuberculosis IS6110 exist in the Amazon; colonization of the oropharynx or of a tuberculous lesion accelerates the growth of the nontuberculous mycobacteria present in the sputum samples, making it impossible to isolate M. tuberculosis; A history of tuberculosis results in positivity for M. tuberculosis DNA. The absence of bacteriological positivity in the presence of polymerase chain reaction positivity raises questions regarding the inherent technical characteristics of the bacteriological methods or regarding patient history of tuberculosis. PMID- 17273614 TI - Cellular and biochemical bases of chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease is an inflammatory disease. Together with oxidant stimuli, which directly affect lung structures, macrophages, neutrophils and CD8+ lymphocytes actively participate in the pathogenesis of the disease and promote biochemical reactions that result in progressive alteration of the upper airways and irreversible lung remodeling. The release of substances promoted by inflammatory cell recruitment and by oxidative stress lead to a temporary imbalance in the pulmonary defense mechanisms. Understanding the long-term maintenance of this imbalance is key to understanding the current physiopathology of the disease. The present study explores the cellular and molecular alterations seen in chronic obstructive pulmonary disease. PMID- 17273615 TI - Idiopathic pulmonary fibrosis: a decade of progress. AB - Although idiopathic pulmonary fibrosis remains a devastating diagnosis, recent advances have improved our understanding of many facets of this disease. These breakthroughs, combined with the increased general availability of therapeutic trials, hold the promise of a brighter future for idiopathic pulmonary fibrosis patients. For example, we now have a more comprehensive understanding of the diagnostic criteria and natural history of the disease. Several studies have shown that simple measurement of pulmonary physiology or gas exchange can be used to predict patient survival. By identifying several molecular pathways that play significant roles in the pathogenesis of idiopathic pulmonary fibrosis, investigators have produced a growing list of novel potential therapeutic targets for the disease. Several prospective, controlled therapeutic trials have been conducted. Others are ongoing or are still in the planning stages. These efforts have advanced our current knowledge of idiopathic pulmonary fibrosis and have raised new important questions, as well as having generated the interest and momentum needed to gain additional ground in the fight against this challenging disease. This article offers the reader a view of the recent advances in idiopathic pulmonary fibrosis research, with a focus on natural history, pathogenesis and treatment. PMID- 17273617 TI - Alveolar adenoma. AB - Alveolar adenoma is a rare benign neoplasm of the lungs, and very few cases have been described in the literature. Patients with alveolar adenoma are frequently asymptomatic and are diagnosed through the accidental discovery of a singular, well-delineated nodule on a routine chest X-ray. The definitive diagnosis is made histologically, and the treatment consists of surgical resection of the nodule. PMID- 17273616 TI - Pulmonary alveolar proteinosis: four cases. AB - OBJECTIVE: The aim of this study was to present the evolution of four patients presenting pulmonary alveolar proteinosis and treated at the State University of Londrina School of Medicine. We focus on the importance of whole-lung lavage as the treatment of choice. METHODS: A retrospective study of four patients, three females and one male, 22 to 34 years old, presenting similar histories of progressive dyspnea and dry cough. The final diagnosis was established through open-lung biopsy. Three of the patients underwent whole-lung lavage in the Department of Surgery. The procedures were performed under general anesthesia and using a double-lumen endotracheal tube. RESULTS: One patient presented spontaneous regression of the pulmonary alveolar proteinosis without the need for whole-lung lavage. In the other three cases, the number of lavages varied: in one patient, a single unilateral lavage resulted in complete remission of the bilateral process; in another patient, three lavages yielded no significant improvement; in the remaining patient, four lavages provided intervening periods of transient improvement. CONCLUSION: In the cases evaluated, whole-lung lavage proved an efficient treatment for pulmonary alveolar proteinosis. Although some patients presented a certain resistance to the procedure, it might lead to complete remission of the disease in others. PMID- 17273619 TI - [Collection and preservation of the pleural fluid and pleural biopsy]. AB - The samples of pleural fluid obtained by thoracentesis for the diagnosis of transudates and exudates shall follow a routine of collection and preservation for an appropriate laboratorial analysis. Equally, fragments of pleura biopsy obtained for the differential diagnosis of the exudates should be collected in a systematic way in order to optimize the diagnosis and facilitate the institution of appropriate therapeutics actions. PMID- 17273618 TI - Dendriform pulmonary ossification. AB - Diffuse pulmonary ossification is a rare condition of unknown pathogenesis in which mature bone is found in the pulmonary parenchyma. It is almost invariably discovered as an incidental finding at autopsy. Most commonly, it affects middle aged men and is asymptomatic. We present the case of a 75-year-old man in which the chest X-ray showed diffuse interstitial infiltrate. Diagnosis was based on histopathological examination by open-lung biopsy, which revealed interstitial fibrosis with pulmonary ossification. PMID- 17273620 TI - [Thoracentesis and pleural biopsy]. AB - Thoracentesis is the method of choice for obtaining samples of pleural fluid. Although it is considered a minimum invasive procedure, it is crucial to follow a standardized technique with the purpose of optimizing the chance of diagnosis and minimizing risks. The pleura biopsy may enlarge and complement the chance of diagnosis of the pleural diseases and is indicated in selected cases. PMID- 17273621 TI - [Tuberculous pleural effusions]. AB - Tuberculous pleural effusion is a common manifestation of the primary form of the disease or consequence of the reactivation of a latent infection due to the M. tuberculosis. Advances in the laboratory methods have contributed to better diagnose and understand the pathophysiology of the effusion secondary to tuberculosis. However, although a predominant lymphocytic pleural effusion is suspicious of tuberculosis, a diagnostic routine shall be instituted to orient treatment and prevent undesirable sequels. PMID- 17273622 TI - [Malignant pleural effusion]. AB - The malignant pleural effusion is a frequent complication in patients with of advanced tumors. The presence of malignant cells in the pleural fluid or in the pleural biopsy is indicative of dissemination of the primary disease, with consequent reduction of life expectancy. The early diagnosis and treatment of the malignant effusion is pivotal in promoting a better quality of life to patients with advanced cancer. PMID- 17273623 TI - [Parapneumonic effusion and empyema]. AB - The infectious effusion, one of the most frequent causes of pleural effusions in the clinical practice, is a sign of complication of the pneumonic disease. The early recognition of the parapneumonic effusion is crucial to determine the best treatment form and reduce the risk of morbidity and mortality. The evolution in the diagnostic methods and the contribution of several studies published in the literature allowed to establish evidence-based guidelines that are used to guide the treatment of the parapneumonic pleural effusion and empyema. PMID- 17273624 TI - [Chylothorax]. AB - Chylothorax, an uncommon cause of pleural effusion, is usually secondary to malignancy, trauma, congenital diseases, infections and superior vena cava thrombosis. The early diagnosis and treatment are important to prevent the most fearful consequence of chylothorax, the malnutrition with a compromised immunological status. PMID- 17273625 TI - [Undiagnosed pleural effusion]. AB - In spite of the progress in the diagnostic methods, about 20% of the pleural effusions may remain without a proper diagnosis after the use of conventional exams. In order to determine the origin of these effusions, alternative methods and invasive procedures shall be used aiming to determine the etiology of the undiagnosed pleural effusions and institute the most appropriate therapeutics. PMID- 17273626 TI - [Pneumothorax]. AB - The presence of free air in the pleural space, or pneumothorax, is a frequent condition in the clinical practice. The therapeutic approach of the pneumothorax depends on the clinical conditions of the patient, the magnitude of the disease and the presence or absence of underlying lung disease. In this chapter we emphasize the diagnostic and therapeutic guidelines for a rational approach of the pneumothorax. PMID- 17273628 TI - [Breastfeeding and obesity in school-age children from families of high socioeconomic status]. AB - OBJECTIVE: To examine the association between breastfeeding and obesity in school age children from Brazilian families of high socioeconomic status. METHODS: A cross-sectional study was conducted including 555 students aged six to 14 years from a private school in the city of Sao Paulo. Obesity - the outcome variable - was defined as body mass index at or above the 85th centile plus sub scapular and triceps skin folds at or above the 90th centile using the sex and age specific standards of the US National Center for Health Statistics. Exposure was the frequency and duration of breastfeeding. Potential confounders, controlled for using multiple logistic regression, included child sex, age, birthweight, and dietary and physical activity patterns, and maternal age, body mass index, schooling, and practice of sports or physical exercise. RESULTS: Prevalence of obesity in the studied population was 26%. After confounder adjustment, the risk of obesity in children that had never been breastfed was twice that of other children (OR=2.06; 95% CI: 1.02; 4.16). There was no dose-response effect of duration of breastfeeding on prevalence of child obesity. CONCLUSIONS: Children who were never breastfed showed greater prevalence of obesity at school age. The absence of a dose-response effect in the relationship between duration of breastfeeding and prevalence of obesity and the still controversial findings regarding this association reported by other authors indicate a need for further studies on the subject, in particular studies with longitudinal design. PMID- 17273629 TI - [Breastfeeding duration in two generations]. AB - OBJECTIVE: To assess the intergenerational repetition of breastfeeding duration in a cohort of adolescent mothers who had been prospectively followed up since birth. METHODS: All hospital births occurred in Pelotas (N=5,914), a Southern Brazilian city, in 1982 were studied prospectively. The cohort was visited in 1984 and 1986, and information on feeding practices was gathered. In 2001, a search was conducted in the Live Birth Information System and adolescents born in 1982 who gave birth between January 1995 and March 2001 were identified. Parous adolescents answered a detailed questionnaire on pregnancy-related variables and breastfeeding duration for each child. For multiparous adolescents, the information from the first live born child was used. Poisson regression with robust adjustment of the variance was used in the univariate and multivariable analysis. RESULTS: A total of 446 parous adolescents belonging to the 1982 cohort were identified, of which 420 (94.2%) were interviewed. After adjustment for confounding variables, mothers who had not been breastfed presented a relative risk of 1.34 (95% CI: 0.35; 5.18) of not breastfeeding their children, compared to mothers who were ever breastfed. Similarly, adolescents who were breastfed for less than one month were slightly - but not significantly - more likely to fail to breastfeed their own infants (RR=1.64; 95% CI: 0.70; 4.03). The proportion of adolescent mothers who breastfed for less than six months was higher among those who were themselves breastfed for less than one month (PR=1.29; 95% CI: 1.02; 1.62)]. CONCLUSIONS: Duration of breastfeeding is slightly higher among infants whose mother was breastfed. PMID- 17273631 TI - Suspected acute toxoplasmosis in pregnant women. AB - OBJECTIVE: To determine the prevalence of reagent serology for suspected acute toxoplasmosis in pregnant women and to describe clinical, laboratory and therapeutic profiles of mothers and their children. METHODS: A retrospective study was conducted with IgM-anti-Toxoplasma gondii-reagent pregnant women and their children who attended the public health system in the state of Parana, Southern Brazil, from January 2001 to December 2003. Information were obtained from clinical, laboratory (ELISA IgM/IgG) and ultrasonographic data and from interviews with the mothers. To test the homogeneity of the IgM indices in relation to the treatment used, the Pearson's Chi-square test was applied. Comparisons were considered significant at a 5% level. RESULTS: Two hundred and ninety (1.0%) cases of suspected IgM-reagent infection were documented, with a prevalence of 10.7 IgM-reagent women per 1,000 births. Prenatal care started within the first 12 weeks for 214/290; 146/204 were asymptomatic. Frequent complaints included headaches, visual disturbance and myalgia. Ultrasonography revealed abnormalities in 13 of 204 pregnancies. Chemoprophylaxis was administered to 112/227; a single ELISA test supported most decisions to begin treatment. Pregnant women with IgM indices =2.000 tended to be treated more often. Among exposed children, 44/208 were serologically followed up and all were IgG-reagent, and three IgM-reagent cases showed clinical symptoms. CONCLUSIONS: The existence of pregnant women with laboratorially suspected acute toxoplasmosis who were not properly followed up, and of fetuses that were not adequately monitored, shows that basic aspects of the prenatal care are not being systematically observed. There is need of implementing a surveillance system of pregnant women and their children exposed to T. gondii. PMID- 17273630 TI - Dietary patterns and risk of oral cancer: a case-control study in Sao Paulo, Brazil. AB - OBJECTIVE: To analyze the association between dietary patterns and oral cancer. METHODS: The study, part of a Latin American multicenter hospital-based case control study, was conducted in Sao Paulo, Southeastern Brazil, between November 1998 and March 2002 and included 366 incident cases of oral cancer and 469 controls, frequency-matched with cases by sex and age. Dietary data were collected using a food frequency questionnaire. The risk associated with the intake of food groups defined a posteriori, through factor analysis (called factors), was assessed. The first factor, labeled "prudent," was characterized by the intake of vegetables, fruit, cheese, and poultry. The second factor, "traditional," consisted of the intake of rice, pasta, pulses, and meat. The third factor, "snacks," was characterized as the intake of bread, butter, salami, cheese, cakes, and desserts. The fourth, "monotonous," was inversely associated with the intake of fruit, vegetables and most other food items. Factor scores for each component retained were calculated for cases and controls. After categorization of factor scores into tertiles according to the distribution of controls, odds ratios and 95% confidence intervals were calculated using unconditional multiple logistic regression. RESULTS: "Traditional" factor showed an inverse association with cancer (OR=0.51; 95% CI: 0.32; 0.81, p-value for trend 0.14), whereas "monotonous" was positively associated with the outcome (OR=1.78; 95% CI: 1.78; 2.85, p-value for trend <0.001). CONCLUSIONS: The study data suggest that the traditional Brazilian diet, consisting of rice and beans plus moderate amounts of meat, may confer protection against oral cancer, independently of any other risk factors such as alcohol intake and smoking. PMID- 17273632 TI - Risk-factors for antepartum fetal deaths in the city of Sao Paulo, Brazil. AB - OBJECTIVE: To assess risk factors for antepartum fetal deaths. METHODS: A population-based case-control study was carried out in the city of Sao Paulo from August 2000 to January 2001. Subjects were selected from a birth cohort from a linked birth and death certificate database. Cases were 164 antepartum fetal deaths and controls were drawn from a random sample of 313 births surviving at least 28 days. Information was collected from birth and death certificates, hospital records and home interviews. A hierarchical conceptual framework guided the logistic regression analysis. RESULTS: Statistically significant factors associated with antepartum fetal death were: mother without or recent marital union; mother's education under four years; mothers with previous low birth weight infant; mothers with hypertension, diabetes, bleeding during pregnancy; no or inadequate prenatal care; congenital malformation and intrauterine growth restriction. The highest population attributable fractions were for inadequacy of prenatal care (40%), hypertension (27%), intrauterine growth restriction (30%) and absence of a long-standing union (26%). CONCLUSIONS: Proximal biological risk factors are most important in antepartum fetal deaths. However, distal factors - mother's low education and marital status - are also significant. Improving access to and quality of prenatal care could have a large impact on fetal mortality. PMID- 17273633 TI - [Support during childbirth: perception of health care providers and companions chosen by women]. AB - OBJECTIVE: To understand health care providers' perception on managing laboring women in the presence of a labor companion of their choice, and the labor companion's perception of this experience. METHODS: A qualitative study was conducted based on a controlled randomized clinical trial. Sampling was intentional and determined through information saturation. Semi-structured interviews were carried out with 11 health care providers and 16 laboring companions in the obstetric unit of a maternity facility at the hospital complex, in Campinas, Southern Brazil, between October 2004 and March 2005. The thematic analysis of discourse was applied using the following methodological figures: central idea, key expressions and discourse of the collective subject. RESULTS: The most remarkable central ideas of health care providers were: no difference was observed in managing laboring women with a labor companion; positive changes were noted in labor management when a labor companion was present; the companion provided emotional support to laboring women who were more pleased, and felt safer and peaceful; many positive aspects were seen in the behavior and involvement of laboring women with a labor companion; the companion caused no problems and encouraged health providers to engage in a more humane and less routine attitude. The main central ideas of labor companions were: positive feelings, emotions, a sense of satisfaction with the experience; being with the laboring woman was a great opportunity to provide her emotional support; and they felt welcome by health care providers. CONCLUSIONS: Health providers considered positive the support provided by a labor companion and had no problems in managing laboring women in the presence of their companions. Labor companions were pleased and happy with this experience. There was no conflicting opinions. PMID- 17273634 TI - [Child depression: anthropological approach]. AB - OBJECTIVE: To understand the sociocultural meanings of childhood depression, from the medical-scientific concept of the disease. METHODS: This was a qualitative study carried out in the metropolitan region of Sao Paulo, State of Sao Paulo, Brazil, in 2003. It consisted of ethnographic observation and in-depth interviews with eight psychiatrists from a public health service and nine relatives (parents or guardians) of children who had been diagnosed with and were being treated for childhood depression. The analysis sought to identify categories that would make it possible to isolate different notions of the disease, as expressed in the discourse of these groups. RESULTS: Different notions of the disease were identified, in accordance with the cultural patterns of the discourse. For the psychiatrists, the concept of childhood depression was related to inappropriate child behavior, or "bad functioning", which then had to be adjusted by medical intervention. For the relatives, childhood depression meant "dissatisfaction" and "discomfort" with life and "intolerance" of adults to child behavior. It was seen that the discourse of the psychiatrists and relatives interviewed showed great diversity of subjects, concepts and categories, according to the logic of their particular understandings and explanations for childhood depression. CONCLUSIONS: In the light of the results obtained, the phenomenon of childhood depression can be analyzed not as an event determined by medical-scientific knowledge, but as a dynamic process of "creative reinvention" of categories and concepts that are fundamental to this discourse. It is therefore concluded that childhood depression presents as a differentiated disease, in the form of a broad category that is capable of integrating different connotations and contexts under the same term. PMID- 17273635 TI - [AIDS, sexuality and attitude of adolescents about protection against HIV]. AB - OBJECTIVE: To describe the role of sexual experience based on information and sociocultural contexts for the risk of HIV/AIDS transmission in adolescents. METHODS: A questionnaire was answered by 1,386 middle school students from the state of Santa Catarina, Southern Brazil, in 2000. The instrument included the following variables: personal characteristics, sexual experience, communication context and knowledge on AIDS, attitudes towards condom use, risk and protective behaviors and feelings. Data analysis comprised statistical description and relational analysis (Chi-square and mean comparison tests). RESULTS: Lack of knowledge about HIV transmission was related to peers as main information source (p<0.05). Steady romantic relationships are the predominant context for sexual relationships with penetration (p<0.001). AIDS protection was associated to three factors: ongoing relationship, number of sexual partners and safe sex (p<0.001). A positive attitude for condom use is favored by talks about sexuality and the intention of condom use (p<0.001). The obstacles to condom use are: having had recent sexual relationships, risk behaviors, inadequate knowledge and dependence of television as an information source (p<0.005). CONCLUSIONS: The practice of safe sex is affected by adolescent's level of information, their attitudes about condom use and fear of the epidemic. Reevaluating prevention through multipliers strategy as well as reappraisal of family as mediators and the use of appropriate materials about Aids for teenagers are recommended. PMID- 17273636 TI - Tracking of physical activity from adolescence to adulthood: a population-based study. AB - OBJECTIVE: To assess the association between regular physical activity in adolescence and leisure-time physical activity in adulthood, with emphasis on gender differences. METHODS: A population-based cross-sectional study was carried out in Pelotas, Southern Brazil, in 2003. A representative sample of households was selected in multiple stages and subjects aged 20-59 years were interviewed. Leisure-time physical activity was evaluated using the International Physical Activity Questionnaire. Data on adolescent physical activity were based on subjects' recall. RESULTS: Of 2,577 subjects interviewed, 27.5% were classified as adequately active, and 54.9% reported regular physical activity in adolescence. Subjects who engaged in regular physical activity during adolescence were more likely to be adequately active in adulthood (adjusted prevalence ratio 1.42; 95% CI: 1.23; 1.65). This effect was stronger in women (adjusted prevalence ratio: 1.51; 95% CI: 1.22; 1.86) than men (adjusted prevalence ratio: 1.35; 95% CI: 1.10; 1.67). CONCLUSIONS: Promoting physical activity in school age may be a successful intervention against the epidemic of adult inactivity. Although women were less likely to report regular physical activity in adolescence, the effect of this experience on adult behavior was stronger than in men. PMID- 17273637 TI - [Reliability of cause of death due to violence from information systems in Belo Horizonte, Southern Brazil]. AB - OBJECTIVE: To determine reliability of data encoding for death due to violence; to assess the agreement between cause of death in the Mortality Information System and cause selected from the Forensic Medicine Institute database; and to assess the impact of adding information of non-specified injuries and undetermined death events subsequently obtained from Forensic Medicine Institute in the mortality statistics due to violence. METHODS: A random sample of 411 death certificates due to violence was obtained in Belo Horizonte, Southeastern Brazil, between 1998 and 2000. Based on data from death certificates and Forensic Medicine Institute database, causes of death were coded and the agreement between this information and that from Mortality Information System was assessed. Also, in all certificates including "non-specified injury" and "undetermined death events," the impact of adding information from Forensic Medicine Institute was assessed in the classification of cause of death. RESULTS: Coding agreement was significant (Kappa=0.782; 95% CI: 0.744; 0.819) and of the underlying cause was moderate to significant (Kappa=0.602; 95% CI: 0.563; 0.641). There were 12.9% and 5.7% misclassification of suicides and murders, respectively, for those causes classified as "non-specified injury" and "undetermined death events," which were overall reduced to 47.3% and 59.8% respectively. CONCLUSIONS: There is a need for further improving the process of underlying cause coding and selection. Also medical examiners need to provide more complete death certificates and medical and police information provided with bodies for Forensic Medicine Institute autopsy should be more complete, especially in those cases of road traffic injuries and falls. PMID- 17273638 TI - [Correction approach for underreporting of deaths and hospital admissions due to ill-defined causes]. AB - OBJECTIVE: To propose a correction approach for underreporting and relocation of ill-defined causes of morbidity and mortality in the National Health System Mortality and Hospital Information Systems. METHODS: Modified James-Stein empirical Bayes estimators for events in delimited geographic areas were applied as a correction approach for underreporting in Brazilian municipalities in 2001. RESULTS: There was an increase of 55,671 deaths in the Mortality Information System, an underreporting correction of 5.85%. It was more effective at the age groups under five (8.1%) and 70 years old and more (6.4%); for neonatal (8.7%) and ill-defined (8.0%) causes of death; and in the states of Maranhao (10.6%), Bahia (9.5%) and Alagoas (8.8%). Relocation of ill-defined causes of mortality changed the structure of proportional mortality in the Northern and Northeastern regions, and increased the proportion of deaths due to cardiovascular diseases and reduced those due to external and neonatal causes. Relocation of ill-defined causes of hospital admissions did not affect hospital proportional morbidity. CONCLUSIONS: The results of underreporting correction were consistent with previous studies, in terms of age groups, causes and geographic areas. Relocation of ill-defined causes of death was spatially consistent. The approach studied may be applicable on Brazilian Health Information since it can be implemented in computational algorithms. Some improvements, however, may be considered, like estimation approaches based on time-space event distribution. PMID- 17273639 TI - [Spatial analysis of neonatal mortality in Paraiba Valley, Southeastern Brazil, 1999 to 2001]. AB - OBJECTIVE: To assess the spatial distribution of neonatal mortality. METHODS: An ecological and exploratory study using a spatial distribution of mortality data approach was carried out in the Paraiba Valley, Southeastern Brazil, from 1999 2001. Spatial analysis was conducted in a georeference database for 35 cities in the region and routines of spatial statistics. Mortality data were obtained from the State of Sao Paulo Health Department. The following variables were analyzed in this study: early, late and total neonatal mortality rates; and Human Development Index (HDI) values per city in 2000. Spatial dependency was measured using global Moran's Coefficients and local Moran's Index. A correlation analysis between variables was also conducted. RESULTS: There were 111,574 newborns with 1,149 deaths in the early neonatal period (10.29/1,000 newborns), 285 in the late neonatal period (2.5/1,000 newborns) totalizing 1,434 neonatal deaths (12.85/1,000 newborns). Estimated global Moran's coefficients showed statistical significance (p<005) for early and total neonatal mortality. Local Moran's index values showed clusters of municipalities for early and total neonatal mortalities rates. CONCLUSIONS: Spatial analysis allowed to identifying spatial clusters for early and total neonatal mortality rates in the central area of the Paraiba Valley. PMID- 17273640 TI - [Safeguarding of the social right to pharmaceutical assistance in the state of Sao Paulo, Brazil]. AB - OBJECTIVE: To evaluate how the Judicial Power safeguards the social right to pharmaceutical assistance as well as the relationships between the legal and political systems to safeguard this right. METHODS: There were assessed decisions in lawsuits of drug supply in the state of Sao Paulo, Southern Brazil, between 1997 and 2004. Discourse of the Collective Subject of procedural actors was the methodological approach used. RESULTS: In 96.4% of the cases analyzed, judges' discourse sentenced the State. In these cases, the State was obliged to provide drugs exactly as requested by the plaintiff, even when drugs were not registered in the National Health Surveillance Agency (9.6% of cases). Also, 100% of the lawsuits were proposed by individual plaintiffs; in 77.4% of the cases the plaintiff requested an specific drug of a specific pharmaceutical company; and in 93,5%, the drugs were provided to the plaintiff through an urgent preliminary order. CONCLUSIONS: The Judicial Power is not taking into account in its decisions political elements of drug policies, established to enforce the social right to pharmaceutical assistance. The Judicial Power is hindering the collective decision making process by the political system, prioritizing plaintiffs' individual needs over community interests. PMID- 17273641 TI - [Drug adverse events in hospitals in the State of Rio de Janeiro, Brazil]. AB - OBJECTIVE: The occurrence of drug adverse events in hospital settings is high and generates cost excess. The purpose of the study was to identify drug-related events during hospital admissions and to estimate their prevalence. METHODS: A retrospective study was carried out in the State of Rio de Janeiro, Southeastern Brazil. Hospitalizations from the Brazilian Health System's national hospital database during the period between 1999 and 2002 were assessed. Admitted cases including suspected drug adverse event cases with ICD-10 (2000) coding in the main diagnosis and/or secondary diagnosis fields were included in the study. Means and standard deviations of continuous variables as well as the statistical significance of differences were estimated using variance analysis (ANOVA with a 95% confidence interval). RESULTS: There were identified 3,421 drug-related adverse events, and a prevalence of 1.8 cases per 1,000 hospitalizations was estimated. Most cases occurred in males (64.5%) admitted in contracted (34.9%) and local public hospitals (23.1%) in the departments of psychiatry (51.4%) and internal medicine (45.2%), of them, 84.1% were discharged. Most of them were adverse drug reactions or drug poisoning, and there were significant difference (p<0.000) regarding age and length of stay between these categories. Patients having adverse events were younger (35.8 vs 40.5 years old) and stayed longer in hospital (26.5 vs 5.0 days). CONCLUSIONS: The frequency of drug adverse events, although lower than those findings of international studies, is significant. National hospital admission database was considered useful in the study of drug related events. PMID- 17273642 TI - [Philanthropic hospitals and the operation of provider-owned health plans in Brazil]. AB - OBJECTIVE: To describe the management performance of philanthropic hospitals that operate their own health plans, in comparison with philanthropic hospitals as a whole in Brazil. METHODS: The managerial structures of philanthropic hospitals that operated their own health plans were compared with those seen in a representative group from the philanthropic hospital sector, in six dimensions: management and planning, economics and finance, human resources, technical services, logistics services and information technology. Data from a random sample of 69 hospitals within the philanthropic hospital sector and 94 philanthropic hospitals that operate their own health plans were evaluated. In both cases, only the hospitals with less than 599 beds were included. RESULTS: The results identified for the hospitals that operate their own health plans were more positive in all the managerial dimensions compared. In particular, the economics and finance and information technology dimensions were highlighted, for which more than 50% of the hospitals that operated their own health plans presented almost all the conditions considered. CONCLUSIONS: The philanthropic hospital sector is important in providing services to the Brazilian Health System (SUS). The challenges in maintaining and developing these hospitals impose the need to find alternatives. Stimulation of a public-private partnership in this segment, by means of operating provider-owned health plans or providing services to other health plans that work together with SUS, is a field that deserves more in-depth analysis. PMID- 17273643 TI - Long-stay patients in a psychiatric hospital in Southern Brazil. AB - OBJECTIVE: To describe the demographic profile, social functioning, and quality of life of a population of long-stay care patients in a psychiatric hospital. METHODS: A study was carried out in Porto Alegre, Southern Brazil, in 2002. A total of 584 (96%) long-stay patients were assessed by means of the following instruments: the World Health Organization Quality of Life, the Social Behavior Schedule, the Independent Living Skills Survey, the Brief Psychiatric Rating Scale and another instrument for assessing disability (Questionnaire for Assessing Physical Disability). RESULTS: The average hospital stay was 26 years (SD: 15.8) and 46.6% of inpatients had no physical disability. Patients had their social functioning skills and autonomy largely impaired. Few of them (27.7%) answered the instrument for assessing quality of life, and showed significant impairments in all domains. The Brief Psychiatric Rating Scale evidenced a low prevalence of positive symptoms in this population. CONCLUSIONS: The institutionalized population studied presented significantly impaired social functioning, autonomy, and quality of life. These aspects need to be taken into consideration while planning for their deinstitutionalization. PMID- 17273644 TI - [Life satisfaction among elderly population in the city of Botucatu, Southern Brazil]. AB - OBJECTIVE: As a result of overall growing population's life expectancy, it has become increasingly important to ensure not only that the elderly have greater longevity but also happiness and life satisfaction. The objective of the study was to describe factors associated with life satisfaction among elderly people. METHODS: Three hundred and sixty-five older persons, selected by means of random stratified proportional sampling, were interviewed in 2003. The instrument used was a combination of Flanagan and Nahas questionnaires and WHOQOL-100. There were added questions concerning physical activity extracted from International Physical Activity Questionnaire, questions regarding reported morbidity and emotional assessment, sociodemographic condition and an open question. The level of life satisfaction was measured using a scale from one to seven by means of visual recognition. Hierarchical logistic regression analysis was performed including "life satisfaction" as a dependent variable and those included the final questionnaire, in blocks, as independent variables. RESULTS: Most elderly were generally rather satisfied with life as well as with specific aspects. The level of life satisfaction was associated with: comfort at home (OR=11.82; 95% CI: 3.27; 42.63); appraising leisure as quality of life (OR=3.82; 95% CI: 2.28; 6.39); waking up feeling well in the morning (OR=2.80; 95% CI: 1.47; 5.36); not reporting loneliness (OR=2.68; 95% CI: 1.54; 4.65); having three or more daily meals (OR=2.63; 95% CI: 1.75; 5.90) and not reporting Diabetes Mellitus (OR=2.63; 95% CI: 1.31; 5.27). CONCLUSIONS: Most elderly in the study were satisfied with life and their satisfaction was associated with situations related to "being well" and not being diabetic. PMID- 17273645 TI - [Social capital and health promotion in Latin America]. AB - Latin America faces common development and health problems and equity and overcoming poverty are crucial in the search for comprehensive and high impact solutions. The article analyzes the definition of social capital, its relationship with health, its limitations and potentialities from a perspective of community development and health promotion in Latin America. High-priority challenges are also identified as well as possible ways to better measure and to strengthen social capital. Particularly, it is discussed how and why social capital may be critical in a global health promotion strategy, where empowerment and community participation, interdisciplinary and intersectorial work would help to achieve Public Health aims and a sustainable positive change for the global development. Also, some potential limitations of the social capital concept in the context of health promotion in Latin America are identified. PMID- 17273647 TI - [Nutritional education and fruit and vegetable intake: a randomized community trial]. AB - We conducted a community trial-type intervention including a sample of 80 families living in a low income neighborhood in the municipality of Sao Paulo, Brazil, in 2004. The intervention relied on nutritional education to increase the participation of fruit and vegetables in the family diet, and was administered in the form of three two-hour meetings during three consecutive weeks. To evaluate the immediate impact of this educational intervention, families were randomly divided into two groups (intervention and control). Only the immediate impact of the intervention was evaluated, based on the participation of fruit and vegetables in the family's total food purchases in the months prior to and following the intervention. The comparison, which was favorable to the intervention group, showed a 2.9 percentage point increase (95% CI: 0.32; 5.39) in the proportion of total calories derived from fruit and vegetables. PMID- 17273646 TI - [Evaluation of quality or qualitative evaluation of health care?]. AB - The paper presents a theoretical exercise regarding health care evaluation in an effort to define several concepts. The multi-dimensional aspects of quality in health are emphasized in addition to the differences between quality evaluation and qualitative evaluation. The implications of not distinguishing between these two concepts are also discussed. Health care is analyzed as a material expression of interpersonal relations in this field and as an object of evaluation, highlighting its intricate relation with integrality and humanization. It is affirmed that quality evaluation and qualitative evaluation are not interchangeable labels, but rather political choices connected to health policies that can not be juxtaposed. Therefore, understanding this distinction is necessary for constructing evaluation proposals that surpass traditional and exclusionary perspectives. PMID- 17273648 TI - [Science, Technology and Health Innovation actions in the Legal Amazon of Brazil]. PMID- 17273649 TI - [Hospital admissions due to external causes in the State of Sao Paulo in 2005]. PMID- 17273652 TI - Abnormal response of left ventricular systolic function to submaximal exercise in post-partial left ventriculotomy patients. AB - Patients with heart failure who have undergone partial left ventriculotomy improve resting left ventricular systolic function, but have limited functional capacity. We studied systolic and diastolic left ventricular function at rest and during submaximal exercise in patients with previous partial left ventriculotomy and in patients with heart failure who had not been operated, matched for maximal and submaximal exercise capacity. Nine patients with heart failure previously submitted to partial left ventriculotomy were compared with 9 patients with heart failure who had not been operated. All patients performed a cardiopulmonary exercise test with measurement of peak oxygen uptake and anaerobic threshold. Radionuclide left ventriculography was performed to analyze ejection fraction and peak filling rate at rest and during exercise at the intensity corresponding to the anaerobic threshold. Groups presented similar exercise capacity evaluated by peak oxygen uptake and at anaerobic threshold. Maximal heart rate was lower in the partial ventriculotomy group compared to the heart failure group (119 +/- 20 vs 149 +/- 21 bpm; P < 0.05). Ejection fraction at rest was higher in the partial ventriculotomy group as compared to the heart failure group (41 +/- 12 vs 32 +/- 9%; P < 0.0125); however, ejection fraction increased from rest to anaerobic threshold only in the heart failure group (partial ventriculotomy = 44 +/- 17%; P = non-significant vs rest; heart failure = 39 +/- 11%; P < 0.0125 vs rest; P < 0.0125 vs change in the partial ventriculotomy group). Peak filling rate was similar at rest and increased similarly in both groups at the anaerobic threshold intensity (partial ventriculotomy = 2.28 +/- 0.55 EDV/s; heart failure = 2.52 +/- 1.07 EDV/s; P < 0.0125; P > 0.05 vs change in partial ventriculotomy group). The abnormal responses demonstrated here may contribute to the limited exercise capacity of patients with partial left ventriculotomy despite the improvement in resting left ventricular systolic function. PMID- 17273651 TI - N-terminal-pro-brain natriuretic peptide, but not brain natriuretic peptide, is increased in patients with severe obesity. AB - Elevated body mass index (BMI) has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m(2), mean age: 39 years) were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m(2), mean age: 43 years). The t test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003) in obese patients (mean 1.67, 95% CI: 1.50 1.83 log pg/mL) compared to controls (mean: 1.32, 95% CI: 1.17-1.47 log pg/mL). The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004). No difference was detected in the Log-BNP concentration (P = 0.63) of obese patients (mean: 0.73, 95% CI: 0.46-1.00 log pg/mL) compared to controls (mean: 0.66, 95% CI: 0.51-0.81 log pg/mL). NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity. PMID- 17273653 TI - Noninvasive prognostic markers for cardiac death and ventricular arrhythmia in long-term follow-up of subjects with chronic Chagas' disease. AB - The objective of the present study was to investigate clinical, echocardiographic and electrocardiographic (12-lead resting ECG, 24-h ambulatory ECG monitoring and signal-averaged ECG (SAECG)) parameters in subjects with chronic Chagas' disease in a long-term follow-up as prognostic markers for adverse outcomes. Fifty adult outpatients (34 to 74 years old, 31 females) staged according to Los Andes class I, II or III and complaining of palpitation were enrolled in a longitudinal study. SAECG was analyzed in time and frequency domains and the endpoint was a composite of cardiac death and ventricular tachycardia. During a follow-up of 84.2 +/- 39.0 months, 34.0% of the patients developed adverse outcomes (9 cardiac deaths and 11 episodes of ventricular tachycardia). After optimal dichotomization, in a stepwise multivariate Cox-hazard regression model, apical aneurysm (HR = 3.7; 95% CI = 1.2-1.3; P = 0.02), left ventricular ejection fraction <62% (HR = 4.60; 95% CI = 1.39-15.24; P = 0.01) and incidence of ventricular premature contractions >614 per 24 h (hazard ratio = 6.1; 95% CI = 1.7-22.6; P = 0.006) were independent predictors of the composite endpoint. Although a high frequency content in SAECG demonstrated association with the presence of left ventricular dysfunction and myocardial fibrosis, its predictive value for the composite endpoint was not significant. Apical aneurysms, reduced left ventricular function and a high incidence of ventricular ectopic beats over a 24-h period have a strong predictive value for a composite endpoint of cardiac death and ventricular tachycardia in subjects with chronic Chagas' disease. PMID- 17273654 TI - Comparison of two questionnaires which measure the health-related quality of life of idiopathic pulmonary fibrosis patients. AB - The objective of the present study was to determine if there is a health-related quality of life (HRQL) instrument, generic or specific, that better represents functional capacity dysfunction in idiopathic pulmonary fibrosis (IPF) patients. HRQL was evaluated in 20 IPF patients using generic and specific questionnaires (Medical Outcomes Short Form 36 (SF-36) and Saint George's Respiratory Questionnaire (SGRQ), respectively). Functional status was evaluated by pulmonary function tests, 6-min walking distance test (6MWDT) and dyspnea indexes (baseline dyspnea index) at rest and after exercise (modified Borg scale). There was a restrictive pattern with impairment of diffusion capacity (total lung capacity, TLC = 71.5 +/- 15.6%, forced vital capacity = 70.4 +/- 19.4%, and carbon monoxide diffusing capacity = 41.5 +/- 16.2% of predicted value), a reduction in exercise capacity (6MWDT = 435.6 +/- 95.5 m) and an increase of perceived dyspnea score at rest and during exercise (6 +/- 2.5 and 7.1 +/- 1.3, respectively). Both questionnaires presented correlation with some functional parameters (TLC, forced expiratory volume in 1 s and carbon monoxide diffusing capacity) and the best correlation was with TLC. Almost all of the SGRQ domains presented a strong correlation with functional status, while in SF-36 only physical function and vitality presented a good correlation with functional status. Dyspnea index at rest and 6MWDT also presented a good correlation with HRQL. Our results suggest that a specific instead of a generic questionnaire is a more appropriate instrument for HRQL evaluation in IPF patients and that TLC is the functional parameter showing best correlation with HRQL. PMID- 17273655 TI - Relevance of apolipoprotein E4 for the lipid profile of Brazilian patients with coronary artery disease. AB - Apolipoprotein E (apoE - e2, e3, e4 alleles) plays a role in the regulation of lipid metabolism, with the e4 considered to be a risk factor for coronary artery disease (CAD). We aimed to evaluate the apoE polymorphisms in Brazilians with CAD and their influence on the lipid profile and other risk factors (hypertension, diabetes mellitus, smoking). Two hundred individuals were examined: 100 patients with atherosclerosis confirmed by coronary angiography and 100 controls. Blood samples were drawn to determine apoE polymorphisms and lipid profile. As expected, the e3 allele was prevalent in the CAD (0.87) and non-CAD groups (0.81; P = 0.099), followed by the e4 allele (0.09 and 0.14, respectively; P = 0.158). The e3/3 (76 and 78%) and e3/4 (16 and 23%) were the most common genotypes for patients and controls, respectively. The lipid profile was altered in patients compared to controls (P < 0.05), independently of the e4 allele. However, in the controls this allele was prevalent in individuals with elevated LDL-cholesterol levels only (odds ratio = 2.531; 95% CI = 1.028-6.232). The frequency of risk factors was higher in the CAD group (P < 0.05), but their association with the lipid profile was not demonstrable in e4 carriers. In conclusion, the e4 allele is not associated with CAD or lipid profile in patients with atherosclerosis. However, its frequency in the non-CAD group is associated with increased levels of LDL-cholesterol, suggesting an independent effect of the e4 allele on lipid profile when the low frequency of other risk factors in this group is taken into account. PMID- 17273656 TI - The effect of an aerobic training program on the electrical remodeling of heart high-frequency components of the signal-averaged electrocardiogram is a predictor of the maximal aerobic power. AB - Increased heart rate variability (HRV) and high-frequency content of the terminal region of the ventricular activation of signal-averaged ECG (SAECG) have been reported in athletes. The present study investigates HRV and SAECG parameters as predictors of maximal aerobic power (VO2max) in athletes. HRV, SAECG and VO2max were determined in 18 high-performance long-distance (25 +/- 6 years; 17 males) runners 24 h after a training session. Clinical visits, ECG and VO2max determination were scheduled for all athletes during the training period. A group of 18 untrained healthy volunteers matched for age, gender, and body surface area was included as controls. SAECG was acquired in the resting supine position for 15 min and processed to extract average RR interval (Mean-RR) and root mean squared standard deviation (RMSSD) of the difference of two consecutive normal RR intervals. SAECG variables analyzed in the vector magnitude with 40-250 Hz band pass bi-directional filtering were: total and 40-microV terminal (LAS40) duration of ventricular activation, RMS voltage of total (RMST) and of the 40-ms terminal region of ventricular activation. Linear and multivariate stepwise logistic regressions oriented by inter-group comparisons were adjusted in significant variables in order to predict VO2max, with a P < 0.05 considered to be significant. VO2max correlated significantly (P < 0.05) with RMST (r = 0.77), Mean-RR (r = 0.62), RMSSD (r = 0.47), and LAS40 (r = -0.39). RMST was the independent predictor of VO2max. In athletes, HRV and high-frequency components of the SAECG correlate with VO2max and the high-frequency content of SAECG is an independent predictor of VO2max. PMID- 17273657 TI - A randomized double-blind clinical trial of the effect of non-absorbable oral polymyxin on infants with severe infectious diarrhea. AB - The present study evaluated the effect of non-absorbable oral polymyxin on the duodenal microflora and clinical outcome of infants with severe infectious diarrhea. Polymyxin was chosen because classic enteropathogenic Escherichia coli was more sensitive to this antibiotic. Twenty-five infants were randomly assigned to a 7-day treatment with oral polymyxin (2.5 mg/kg in 4 daily doses) or placebo. Duodenal and stool cultures were performed before and after the treatment. Five patients were excluded during the study because of introduction of parental antibiotic therapy due to clinical sepsis (N = 3) or rapid clinical improvement (N = 2). In the polymyxin group, small bowel bacterial overgrowth occurred in 61.5% of the cases (8/13) before treatment and in 76.9% (10/13) after treatment. In the placebo group these values were 71.4% (5/7) and 57.1% (4/7), respectively. By the 7th day, clinical cure was observed in 84.6% of the cases (11/13) in the polymyxin group and in 71.4% (5/7) in the placebo group (P = 0.587). Considering all 25 patients included in the study, clinical cure occurred on the 7th day in 12/14 cases (85.7%) in the polymyxin group and 6/11 cases (54.5%) in the placebo group (P = 0.102). Clinical sepsis occurred in 3/11 (27.3%) of the patients in the placebo group and in none (0/14) in the polymyxin group (P = 0.071). Oral polymyxin was not effective in reducing bacterial overgrowth or in improving the clinical outcome of infants hospitalized with severe infectious diarrhea. Taking into account the small sample size, the rate of cure on the 7th day and the rate of clinical sepsis, further studies with greater number of patients are necessary to evaluate these questions. PMID- 17273658 TI - Lack of relationship between glycemic control and bone mineral density in type 2 diabetes mellitus. AB - We assessed the effect of chronic hyperglycemia on bone mineral density (BMD) and bone remodeling in patients with type 2 diabetes mellitus. We investigated 42 patients with type 2 diabetes under stable control for at least 1 year, 22 of them with good metabolic control (GMC: mean age = 48.8 +/- 1.5 years, 11 females) and 20 with poor metabolic control (PMC: mean age = 50.2 +/- 1.2 years, 8 females), and 24 normal control individuals (CG: mean age = 46.5 +/- 1.1 years, 14 females). We determined BMD in the femoral neck and at the L2-L4 level (DEXA) and serum levels of glucose, total glycated hemoglobin (HbA1), total and ionic calcium, phosphorus, alkaline phosphatase, follicle-stimulating hormone, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OH-D), insulin-like growth factor I (IGFI), osteocalcin, procollagen type I C propeptide, as well as urinary levels of deoxypyridinoline and creatinine. HbA1 levels were significantly higher in PMC patients (12.5 +/- 0.6 vs 7.45 +/- 0.2% for GMC and 6.3 +/- 0.9% for CG; P < 0.05). There was no difference in 25-OH-D, iPTH or IGFI levels between the three groups. BMD values at L2-L4 (CG = 1.068 +/- 0.02 vs GMC = 1.170 +/- 0.03 vs PMC = 1.084 +/- 0.02 g/cm(2)) and in the femoral neck (CG = 0.898 +/- 0.03 vs GMC = 0.929 +/- 0.03 vs PMC = 0.914 +/- 0.03 g/cm(2)) were similar for all groups. PMC presented significantly lower osteocalcin levels than the other two groups, whereas no significant difference in urinary deoxypyridine was observed between groups. The present results demonstrate that hyperglycemia is not associated with increased bone resorption in type 2 diabetes mellitus and that BMD is not altered in type 2 diabetes mellitus. PMID- 17273660 TI - Random amplification of polymorphic DNA reveals clonal relationships among enteropathogenic Escherichia coli isolated from non-human primates and humans. AB - Enteropathogenic Escherichia coli (EPEC) strains are important agents of infantile diarrhea all over the world, gaining even greater importance in developing countries. EPEC have also been isolated from various animal species, but most isolates belong to serotypes that differ from those recovered from humans. However, it has been demonstrated that several isolates from non-human primates belong to the serogroups and/or serotypes related to those implicated in human disease. The objective of this study was to evaluate the genetic differences between thirteen strains isolated from non-human primates and the same number of strains isolated from human infections. Human isolates belonged to the same serogroup/serotype as the monkey strains and the evaluation was done by analysis of random amplified polymorphic DNA. Dendrogram analysis showed that there was no clustering between human and monkey strains. Human and non-human isolates of the EPEC serotypes O127:H40 and O128:H2 shared 90 and 87% of their bands, respectively, indicating strong genomic similarity between the strains, leading to the speculation that they may have arisen from the same pathogenic clone. To our knowledge, this study is the first one comparing genomic similarity between human and non-human primate strains and the results provide further evidence that monkey EPEC strains correlate with human EPEC, as suggested in a previous investigation. PMID- 17273659 TI - Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity? AB - In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP) levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m(2) and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20) or metformin, 1.7 g/day (N = 21) for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 +/- 0.04 mg/dL (P = 0.002) over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data. PMID- 17273661 TI - Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy. AB - Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients. PMID- 17273662 TI - Epidemiological characterization of resistance and PCR typing of Shigella flexneri and Shigella sonnei strains isolated from bacillary dysentery cases in Southeast Brazil. AB - Shigella spp are Gram-negative, anaerobic facultative, non-motile, and non sporulated bacilli of the Enterobacteriaceae family responsible for "Shigellosis" or bacillary dysentery, an important cause of worldwide morbidity and mortality. However, despite this, there are very few epidemiological studies about this bacterium in Brazil. We studied the antibiotic resistance profiles and the clonal structure of 60 Shigella strains (30 S. flexneri and 30 S. sonnei) isolated from shigellosis cases in different cities within the metropolitan area of Campinas, State of Sao Paulo, Brazil. We used the following well-characterized molecular techniques: enterobacterial repetitive intergenic consensus, repetitive extragenic palindromic, and double-repetitive element-polymerase chain reaction to characterize the bacteria. Also, the antibiotic resistance of the strains was determined by the diffusion disk method. Many strains of S. flexneri and S. sonnei were found to be multi-resistant. S. flexneri strains were resistant to ampicillin in 83.3% of cases, chloramphenicol in 70.0%, streptomycin in 86.7%, sulfamethoxazole in 80.0%, and tetracycline in 80.0%, while a smaller number of strains were resistant to cephalothin (3.3%) and sulfazotrim (10.0%). S. sonnei strains were mainly resistant to sulfamethoxazole (100.0%) and tetracycline (96.7%) and, to a lesser extent, to ampicillin (6.7%) and streptomycin (26.7%). Polymerase chain reaction-based typing supported the existence of specific clones responsible for the shigellosis cases in the different cities and there was evidence of transmission between cities. This clonal structure would probably be the result of selection for virulence and resistance phenotypes. These data indicate that the human sanitary conditions of the cities investigated should be improved. PMID- 17273663 TI - Tetanus and diphtheria immunity in adolescents from Sao Paulo, Brazil. AB - Tetanus and diphtheria vaccines are of special concern in adolescents because boosters are necessary for adequate maintenance of protection and are often omitted. We assessed serum levels of tetanus and diphtheria antibodies in adolescents and their association with vaccination status. From May to October 2001, we evaluated the vaccination records of 208 adolescents aged 10 to 20 years in Sao Paulo, Brazil. Antibodies to tetanus and diphtheria were detected using double-antigen ELISA and vaccination records were analyzed according to the guidelines of the Brazilian National Immunization Program. All adolescents had received complete primary vaccinations against tetanus and diphtheria, but 23.1% of them had not received a booster dose in the last 10 years. All adolescents were immune to tetanus and 88.9% were fully protected (antibodies (3)0.1 IU/mL). One individual (0.5%) was non-immune to diphtheria and 86% were fully protected against the disease. Adolescents with up-to-date vaccination records had higher antibody levels than those with not up-to-date records for tetanus (0.763 vs 0.239 IU/mL, t-test: P < 0.0001) and diphtheria (0.366 vs 0.233 IU/mL, t-test: P = 0.014). Full immunity against tetanus (antibodies (3)0.1 IU/mL) was higher among individuals with up-to-date vaccination (93.1%) when compared to those with not up-to-date records (75%, Fisher's exact test: P = 0.001). All adolescents had received basic immunization in childhood and were protected against tetanus and diphtheria. However, these data indicate that more emphasis should be placed on the tetanus-diphtheria booster in order to avoid a decay in antibody levels. PMID- 17273664 TI - Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma. AB - It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4%), 24 (46.2%) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4% CC, 42% GC and 54% GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM. PMID- 17273665 TI - Comorbidity of psychiatric disorders and symmetric distal polyneuropathy among type II diabetic outpatients. AB - The objective of the present study was to establish the frequency of psychiatric comorbidity in a sample of diabetic patients with symmetric distal polyneuropathy (SDPN). Sixty-five patients with type 2 diabetes mellitus were selected consecutively to participate in the study at Instituto Estadual de Diabetes e Endocrinologia. All patients were submitted to a complete clinical and psychiatric evaluation, including the Portuguese version of the structured clinical interview for DSM-IV, the Beck Depression Inventory, the Neuropathy Symptom Score, and Neuropathy Disability Score. SDPN was identified in 22 subjects (33.8%). Patients with and without SDPN did not differ significantly regarding sociodemographic characteristics. However, a trend toward a worse glycemic control was found in patients with SDPN in comparison to patients without SDPN (HbA1c = 8.43 +/- 1.97 vs 7.48 +/- 1.95; P = 0.08). Patients with SDPN exhibited axis I psychiatric disorders significantly more often than those without SDPN (especially anxiety disorders, in general (81.8 vs 60.0%; P = 0.01), and major depression--current episode, in particular (18.2 vs 7.7%; P = 0.04)). The severity of the depressive symptoms correlated positively with the severity of SDPN symptoms (r = 0.38; P = 0.006), but not with the severity of SDPN signs (r = 0.07; P = 0.56). In conclusion, the presence of SDPN seems to be associated with a trend toward glycemic control. The diagnosis of SDPN in diabetic subjects seems also to be associated with relevant psychiatric comorbidity, including anxiety and current mood disorders. PMID- 17273666 TI - Muscular function and functional mobility of faller and non-faller elderly women with osteoarthritis of the knee. AB - Falls are a major concern in the elderly population with chronic joint disease. To compare muscular function and functional mobility among older women with knee osteoarthritis with and without a history of falls, 15 elderly women with a history of falls (74.20 +/- 4.46 years) and 15 without a history of falls (71.73 +/- 4.73 years) were studied. Muscular function, at the angular speed of 60, 120, and 180 masculine/s, was evaluated using the Biodex Isokinetic Dynamometer. The sit-to-stand task was performed using the Balance Master System and the Timed Up and Go test was used to determine functional mobility. After collection of these data, the history of falls was investigated. A statistically significant difference was detected in the time taken to transfer the center of gravity during the sit-to-stand test (means +/- SD; non-fallers: 0.35 +/- 0.16 s; fallers: 0.55 +/- 0.32 s; P = 0.049, Student t-test) and in the Timed Up and Go test (medians; non-fallers: 10.08 s; fallers: 11.59 s; P = 0.038, Mann-Whitney U test). The results indicated that elderly osteoarthritic women with a history of falls presented altered functional mobility and needed more time to transfer the center of gravity in the sit-to-stand test. It is important to implement strategies to guarantee a better functional performance of elderly patients to reduce fall risks. PMID- 17273667 TI - [Ethics, research and scientific publishing]. PMID- 17273670 TI - [Evaluation of performance, efficacy and safety of semi-automated lamellar keratoplasty]. AB - PURPOSE: To evaluate the feasibility, efficacy and safety of a manual microkeratome and an artificial anterior chamber for lamellar keratoplasty (ALTK system). METHODS: Twenty-one eyes with superficial corneal opacities were submitted to semi-automated lamellar keratectomy. In recipient eyes keratectomy was performed as in refractive surgery. The donor flap was removed from the preserved corneal shell using the same microkeratome and an artificial anterior chamber. Lamella thickness was measured through ultrasound biomicroscopy (UBM) after surgery. RESULTS: The surgeries were accomplished successfully in 19 eyes. 80% of the flaps obtained in donated corneas and 84.2% of the flaps in recipient eyes had an up to 0.5 mm variation variation of the desired diameter. A high similarity in flap thickness between the donor flap and the recipient cornea was obtained. Postoperative visual acuity of 20/40 or better was observed in 52.6% of the eyes. Complications such as undesired diameter of the flap, a case of perforation in the recipient eye and a case of cornea ectasia were observed. CONCLUSION: The semi-automated lamellar keratoplasty ALTK system showed to be feasible due to the predictability and reproducibility regarding lamella thickness and diameter, efficient in the improvement of postoperative visual acuity and safe due to the low level surgical complication. PMID- 17273669 TI - [Clinical characteristics and incidence of infectious and non-infectious endophthalmitis after intravitreous injection of triamcinolone acetonide]. AB - PURPOSE: To report the incidence of infectious and noninfectious endophthalmitis after intravitreal injection of 4 mg of triamcinolone acetonide (Kenalog - 40 mg/ml; 0.1 ml) and to evaluate distinguishing characteristics that may assist the clinician in differentiating these entities. DESIGN: Observational nonconcurrent prospective study. METHODS: Charts of 121 patients (154 injections) who consecutively underwent intravitreal injection of triamcinolone acetonide to treat various chorioretinal diseases were evaluated. All procedures were performed in an operating room with careful antiseptic protocol. RESULTS: Two eyes (1.29%/injection and 1.65%/patient) presented a noninfectious endophthalmitis characterized by decreased vision, hyperemia, hypopyon and vitreous inflammatory reaction, on the first day after the injection. These eyes were treated with topical and subconjunctival corticosteroids with complete resolution of the inflammatory reaction. CONCLUSION: In the present case series, no case of infectious endophthalmitis occurred. Despite being relatively rare, noninfectious endophthalmitis can be associated with intravitreal injection of triamcinolone simulating an infectious endophthalmitis. In selected cases, the differential diagnosis can be made solely by clinical evaluation. PMID- 17273671 TI - Anterior ischemic optic neuropathy: a comparison of the optic disc area of patients with the arteritic and non-arteritic forms of the disease and that of normal controls. AB - PURPOSE: To evaluate the optic disc area of patients with non-arteritic anterior ischemic optic neuropathy (NA-AION) and arteritic anterior ischemic optic neuropathy (A-AION) and compare the results between each other and with those from controls in order to verify the existence and the magnitude of anatomical factors predisposing to the development of anterior ischemic optic neuropathy. METHODS: This is a case-controlled study of the optic disc area of 24 consecutive patients affected with NA-AION, 13 patients with A-AION and 24 consecutive healthy normals, sex- and age-matched with the patients with the NA-AION group. Measurements of optic disc area were performed for each studied group using disc photographs projected, measured and corrected for the refractive error and the keratometric readings, according to Littmann's method in each studied group. The results were compared using variance analysis. RESULTS: The mean areas and standard deviations of the optic discs from patients with NA-AION, A-AION and normals were respectively 1.99 +/- 0.35 mm(2), 2.29 +/- 0.39 mm(2) and 2.49 +/- 0.53 mm(2). The statistical analysis revealed that the mean areas of the optic disc of patients with NA-AION were significantly different from those of normal controls. No statistical difference was found between A-AION and normal controls. CONCLUSION: NA-AION occurs predominantly in small discs while the arteritic form of the disease shows no such preference. Factors related to optic disc structure play a role in the pathophysiology of NA-AION. The occurrence of AION in large optic optic discs should raise the suspicion of temporal arteritis. On the other hand, small optic disc areas do not rule out that vasculitis. PMID- 17273672 TI - Colchicine in the treatment of the inflammatory phase of Graves' ophthalmopathy: a prospective and randomized trial with prednisone. AB - PURPOSE: To investigate if colchicine is valuable in the treatment of Graves' ophthalmopathy (GO), we compared its effect with prednisone in 22 patients during the inflammatory phase of GO. METHODS: All patients, similar in age, sex and smoking habits, were euthyroid for at least 3 months and randomly divided into two groups, one treated with colchicine (1.5 mg/day) and the other treated with prednisone (0.75 mg/kg/day). They were monitored with ophthalmologic assessment (clinical activity score-CAS) and magnetic resonance imaging, using a signal intensity ratio (SIR) of the recti muscles in comparison to the cerebral substantia alba. RESULTS: Amelioration of CAS was seen in 68% of the orbits in both groups. SIR also had a significant reduction after treatment: the initial median of 1.14 in G1 and 1.27 in G2, evolved, after treatment, to 1.07 in G1 and 0.69 in G2. The variation between both groups after treatment was not significant (p=0.22). None of the patients treated with colchicine had side effects; on the other hand, side effects in G2 were weight gain, edema, gastric complaints, hirsutism, weakness, depression, and alterations in blood pressure. CONCLUSION: Colchicine had a beneficial effect on the inflammatory phase of GO without the side effects of prednisone. PMID- 17273673 TI - [Clinical and morphometric evaluations of the angiogenic capacity of chitosan membrane in rabbit corneas]. AB - PURPOSE: To evaluate corneal vascularization (CV) induced by interlamellar graft chitosan membrane (CM) in rabbit cornea. METHODS: An interlamellar graft with a 0.25 x 0.25 cm CM fragment was performed in the left eye (treated eye). In the right eye, an estromal tunnel was done (control eye). The clinical evaluation was done at 1, 3, 7, 15 and 30 days postoperatively. CV analysis was after 30 days by the Image Analyzer System LEICA QWIN-550. RESULTS: After 7 days, CV at 1.5+/-0.92 mm from the limbus in direction of the cornea axial area was observed. After 15 days CV increased (4.75+/-3.19 mm), remaining until day 30 (4.25+/-4.06 mm). The control eyes did not present any changes. There was a statistical differences of the vascularizated corneal areas between control and treated eyes from the 15th to the 30th postoperative day. CONCLUSION: The chitosan membrane induced corneal angiogenesis when applied to rabbit cornea through an interlamellar graft, which was maintained at low levels until 30 days postoperatively. Although further studies are necessary, the results found here demonstrated the usefulness of chitosan membrane in keratoplasties. PMID- 17273674 TI - [Detection of subclinical hypotony maculopathy with OCT III after filtration surgery]. AB - PURPOSE: To detect nondiagnostic hypotony maculopathy by OCT III after filtration surgery. METHODS: After surgery, patients with intraocular pressure less than 9 mmHg were submitted to OCT III examination. RESULTS: Seven (87.50%) patients with previous diagnosis of open angle glaucoma and one (12.50%) of them with acute angle closure glaucoma. Two patients (25.00%) presented hypotony maculopathy on OCT III examination. CONCLUSION: OCT III examination seems to be a good diagnostic method to detect subclinical hypotony maculopathy after filtration surgery. PMID- 17273675 TI - [Congenital ptosis associated with fatty infiltration of levator eyelid muscle]. AB - PURPOSE: To quantify the fat in the levator muscle of patients with congenital ptosis, as related to clinical and epidemiological aspects of this disease. METHODS: Twenty-two levator muscle samples of the superior eyelid from patients with congenital ptosis were morphometrically evaluated with aim of establishing a relationship between the fat quantity and age, sex, ptosis degree and levator muscle function. RESULTS: According to our results the fat in the levator muscle of patients with congenital ptosis is not related to gender or epidemiologic aspects. CONCLUSION: Fat amount in the levator muscle from congenital ptosis is not related to age, sex, ptosis degree or levator muscle function. Other studies will be necessary to show the real alterations in the levator muscle related to eyelid ptosis. PMID- 17273676 TI - [Exposure of Tenon's capsule fibroblasts of pterygium to cyclosporin 0.05%]. AB - PURPOSE: To evaluate normal Tenon capsule fibroblasts and from pterygia in culture when exposed to cyclosporin 0.05%. METHODS: A prospective, randomized study was done, involving 20 patients with primary pterygium. Samples of normal and pterygium Tenon's capsule from the same individual were collected, cultured and exposed to cyclosporin 0.05%. RESULTS: Only 7 samples could be exposed to cyclosporin--6 from pterygial Tenon's capsule and 1 from normal Tenon's capsule. There was a significant reduction of cellular proliferation in the cyclosporin exposed cultures (p<0.05). CONCLUSION: Cyclosporin 0.05% is effective to inhibit the proliferation of pterygia and normal Tenon's capsule fibroblasts. Further studies should be performed to define the role of cyclosporin in pterygium treatment. PMID- 17273677 TI - [Angiography: safety x economy]. AB - PURPOSE: To evaluate the safety, effectiveness, and cost of angiofluoresceinographic examination by using both the least amount of dye as well as digital equipment along with a laser photocopier. METHODS: Prospective and comparative study carried out in a group of 70 patients, who underwent an angiographic evaluation with a conventional retinographer injecting 5 ml sodium fluorescein at 10% (control group) as well as a group of 70 patients who underwent an angiographic evaluation with a digital retinographer injecting 2 ml fluorescein at 10% (study group). Arterial pressure, heart rate and oximetry were assessed prior to and after the dye injection. Organic reactions related to the examination were reported. Photograph quality as well as cost between the two techniques were compared. RESULTS: Control group patients showed a greater increase in systolic and diastolic arterial pressure. Heart rate, oximetry measurement and adverse reactions did not show any significant statistical differences between both groups. As for the quality of photographs, a better performance was noticed in the control group. As for the cost, the examination carried out in the study group required lower cost and thus saved around 54.8% per examination in relation to the control group. CONCLUSION: The examination carried out with a lower dose of fluorescein using digital equipment along with a laser photocopier provided greater stability in the systolic and diastolic arterial pressure. However, it did not have any influence on heart rate, oximetry or adverse reactions such as nausea, vomiting, syncope and rashes. The quality of photographs was poor although they enabled diagnosis as well as therapy follow-up for those who carried out the examination. Moreover, economically the above procedure represented a gain of 66.26%, against 25.81% in relation to the conventional equipment. PMID- 17273678 TI - [Examination of blades used in LASIK by scanning electron microscopy]. AB - PURPOSE: To evaluate and compare, by scanning electron microscopy (SEM), the sharpness of the edge of brand new surgical blades and consecutively used surgical blades in laser-assisted in situ keratomileusis (LASIK). METHODS: Twenty five AccuGlide (Bausch & Lomb, USA) surgical blades were evaluated, divided into 3 groups: Group 1 (control), non-used surgical blades; Group 2, ten surgical blades used twice (simultaneous bilateral procedure); Group 3, ten surgical blades used four times (two consecutive simultaneous bilateral procedures). Each blade was analyzed by SEM at four random points, two central and two peripheral points, with magnification of 50x, 350x, and 1,000x. RESULTS: Blade body irregularities and organic material were observed on all used surgical blades (Groups 2 and 3), but not on new surgical blades (Group 1). In addition, Group 3 revealed more irregularities in both central (p=0.0094) and peripheral points (p=0.0098) than Group 2, as well as organic material deposition (p=0.0204 and p=0.0909, respectively). Neither metallic material nor irregularities in the cutting edge of the blade were observed in any group. CONCLUSION: No difference regarding the cutting edge was observed between new and blades reused up to four times, however irregularities and organic material were observed in all reused blades. Reusing blades for LASIK may produce structural changes and its clinical implications need to be evaluated due to the possible relation with interlamellar postoperative complications. PMID- 17273679 TI - [Comparative study between 0.025% ketotifen fumarate and 0.1% olopatadine hydrochloride in the treatment of vernal keratoconjunctivitis]. AB - PURPOSE: To compare the topical use of 0.025% ketotifen fumarate and 0.1% olopatadine hydrochloride in the treatment of patients with vernal keratoconjunctivitis. METHODS: A study performed in one center, simple masked, parallel-group compared ketotifen and olopatadine. These patients were evaluated on four visits during the treatment (days 1, 7, 14 and 21), defined by ratings scores. Adverse events were the main variable of safety rating. RESULTS: On evaluating ocular itching, burning, tearing, conjunctival hyperemia, mucous discharge and photophobia, the ketotifen group showed a significant improvement of total signs and symptoms (p<0.05). Between the baseline and the 2nd visit, treatment with olopatadine resulted in decreased burning, but after the 4th visit, ketotifen was slightly better. Sand sensation, papillae and Horner-Trantas dots were not significantly different in both groups. CONCLUSION: Both drugs were efficient and safe relieving the main symptoms and signs of vernal keratoconjunctivitis. Between the same timepoints, there was a significant difference in favor of ketotifen-treated patients (p<0.05), showing improvement of itching, tearing, conjunctival hyperemia, mucous discharge and photophobia. PMID- 17273680 TI - [Electroretinographic study of chromatic vision]. AB - PURPOSE: To describe the electroretinogram of the South-American opossum (Didelphis aurita) obtained by chromatic stimulus of specific wavelengths. The electroretinogram records voltage variations of retinal cells triggered by light stimulation. The electroretinogram represents the combination of electric activity of many different cells and varies according to retinal physiology and examination methods. METHODS: We recorded the electroretinogram of six animals in dark adaptation using chromatic Kodak Wratten filters, and recorded the spectral sensitivity to specific wavelengths in the spectrum of blue, green, yellow, orange and red light bands. RESULTS: The most consistent electrorretinographic results were obtained when the animals were stimulated by selective spectral bands instead of white light. These results are consistent with the absorbance curve of the opsins described in marsupial photoreceptors. Previous studies using microspectrophotometry of opsins and retinal immunohistochemistry suggested marsupial trichromacy. This morphologic knowledge has not before been physiologically demonstrated by electroretinographic methods. CONCLUSION: The South-American opossum has proven to be an interesting experimental animal for comparative visual physiology studies among other mammals, especially studies on phylogenetic of chromatic vision. The opossum represents a retinal model that superimposes both the photopic and scotopic systems; and the Didelphis genus shows few changes when compared to the fossils of the Pleocene period. Therefore the marsupial's visual system retrieves characteristics from ancient mammal evolution to the retinal patterns found in modern mammals. PMID- 17273681 TI - [Conjunctival bacilloscopy in leprosy diagnosis and follow-up]. AB - PURPOSE: To identify Mycobacterium leprae in ocular conjunctivae and evaluate conjunctival bacilloscopy as leprosy diagnosis and follow-up test. METHODS: We used the superior tarsal conjunctiva scraping technique in 52 newly diagnosed leprosy patients between July and September 2004 at the "Oculistas Associados de Brasilia", in Brasilia, DF, Brazil, and compared the conjunctival bacilloscopy with skin bacilloscopy. RESULTS: Both the conjunctival bacilloscopy index (CBI) and skin bacilloscopy index (SBI) showed correlation since Pearson's r and Cohen kappa measure of agreement were respectively 76.3% (p<0.01) and 0.615 (p<0.01). Pearson chi-square also evidenced the correlation (p<0.01). Comparison of CBI and SBI (17 cases of positive CBI out of 26 SBI) gives a sensitivity of 65.4% (CI95% 0.519-0.690); 25 cases of positive CBI out of 26 cases of negative SBI give a specificity of 96.2% (CI95% - 0.826-0.998); positive predictive value of 94.4%; negative predictive value of 73.5%, and accuracy of 80.8%. Likelihood ratio was 17. Mean time to eliminate the bacilli from conjunctiva was 5 months (CI95% - 3.57-6.43). CONCLUSION: We suggest the use of conjunctival bacilloscopy in addition with skin bacilloscopy to confirm leprosy diagnosis. Conjunctival bacilloscopy may also be useful for treatment follow-up in leprosy. PMID- 17273682 TI - [Study of retinal nerve fiber layer in patients with schistosomiasis mansoni: analysis with GDX]. AB - PURPOSE: To study the retinal nerve fiber layer in young patients suffering from hepatosplenic schistosomiasis mansoni. METHODS: Twenty-three patients with hepatosplenic schistosomiasis mansoni who were submitted, when children, to splenectomy, ligature of the left gastric vein and auto-implantation of spleen tissue in the major omentum underwent GDx Scanning Laser System evaluations. All patients presented with intraocular pressure below 21 mmHg. RESULTS: Only one patient suffering from hepatosplenic schistosomiasis mansoni showed abnormalities on the GDx examination. There were no abnormalities on GDx examination in the control group. CONCLUSION: There was no significant difference between the two groups of this study. Only one patient showed retinal nerve fiber layer reduction. PMID- 17273683 TI - [Comparative study of the biometric measurements made by immersion and contact techniques]. AB - PURPOSE: To compare clinical biometric findings between measurements of immersion technique and contact technique. METHODS: Axial length was measured by A-scan in 120 medical examinations in 60 patients with cataract using a non-contact (immersion) and a contact technique in paired-samples by ultrasound. RESULTS: The mean axial length was found to be 23.19 mm (SD 1.32) with the immersion technique and 22.93 mm (SD 1.32) with the contact technique, using the same transducer probe. The difference of 0.255 mm (SD 0.3) was significant at the 0.01 level. The difference should be taken into account when evaluating the accuracy of IOL calculation. The mean standard deviation between recurrent measures in same eye was found to be 0.04 with the immersion technique and 0.19 with the contact technique. The difference of 0.15 was significant at the 0.01 level. The difference should be taken into account when evaluating the accuracy of reproductivity of technique examination. CONCLUSION: These data provide benchmark information that can be used to monitor clinical practice and to perform others studies. PMID- 17273684 TI - [Genetic and ophthalmological assessment of patients with type II Stickler syndrome]. AB - PURPOSE: To diagnose, evaluate and describe the clinical, genetic and ophthalmic characteristics of a family with type II Stickler syndrome. METHODS: X-rays for bone age, clinical and genetic evaluation were performed in all patients with ocular alterations. The Stickler syndrome diagnosis was established after correlating these examinations. RESULTS: Type II Stickler syndrome was found in 11 patients. The most important ocular findings were: high myopia (80%), lens subluxation (70%), exotropia (50%) and vitreoretinal abnormalities (80%) including vitreous cavity (50%). The clinical genetic examination disclosed that 30% of the patients had micrognathia, 50% hearing loss, 40% nasal depression and 60% high palate. Seven cases had articular hypermotility and long fingers and arthropathy was present in 3 cases. CONCLUSION: Diagnosis of the Stickler syndrome is difficult due to its phenotypic variability and the existence of other genetic syndromes with similar characteristics. Hand and wrist radiographs are of particular importance in the diagnosis of this syndrome. PMID- 17273685 TI - [Psychological aspects and quality of life in uveal melanoma patients during the treatment process by ocular bulb remotion]. AB - PURPOSE: To evaluate prospectively the emotional repercussions in the individual with uveal melanoma and surgical indication in three phases: diagnosis and preoperative, postsurgery and late postsurgery. METHODS: Clinical qualitative study based on the following instruments: STAI--State, Trait Anxiety Inventory; BDI--Beck Depression Inventory; Quality of Life Questionnaire SF-36. RESULTS: The sample of this study consisted of 20 patients, 13 males and seven females, with average age of 52 years. Before surgery: the patients appear fragile and impacted by diagnosis and treatment. The state of depression indicates a minimum to light state. Anxiety has the state increased in relationship to Trait. Quality of Life has the emotional and physical aspects affected. Three months after surgery: the Depression shows to light to serious state. Anxiety has the state considerably increased. Quality of Life has most aspects affected: the physical, vitality, social, mental health and emotional aspects being the most affected. One year after surgery: the State of Anxiety decreases considerable. The Trait of Anxiety is maintained in most patients when compared to the first evaluation. Depression shows a minimum state. Quality of Life has most of its aspects balanced. CONCLUSION: After three months of surgery the patients appear more fragile with adaptation difficulty, Anxiety and Depression increasing. This period revealed to be the worst moment. One year after surgery, they appear more structured and with a more balanced Quality of Life. PMID- 17273686 TI - [Clinical and electroretinographic profile of commotio retinae]. AB - PURPOSE: To investigate clinical, anatomic and electroretinographic changes in eyes that suffered blunt ocular trauma with commotio retinae. METHODS: Patients who presented commotio retinae after unilateral blunt ocular trauma less then 72 hours before were submitted to visual acuity testing, biomicroscopy, binocular indirect ophthalmoscopy, fluorescein angiography, optical coherence tomography and full-field electroretinography. Full-field ERG was repeated after 15 and 30 days. RESULTS: Sixteen patients were included in the study. On the first examination there was a statistically significant difference between affected and fellow eye in all response amplitudes, without b/a ratio alteration, and a delay in single-flash cone response and 30-Hz flicker implicit time. On the second examination, the difference between the eyes remained for oscillatory potentials, but disappeared on the last examination. In fluorescein angiography, all patients presented mottled hyperfluorescence and hypofluorescent areas, due to alterations in the pigment barrier. On optical coherence tomography, we found optically empty spaces at the site of the lesion. CONCLUSION: Found changes suggested photoreceptor and ganglion cells, but not Muller cell functional alterations, as well as pigment mobilization. These changes disappeared 30 days after the trauma. PMID- 17273687 TI - [A computerized method for visual acuity assessment]. AB - PURPOSE: To elaborate and to validate a computerized test for visual acuity screening of school-age children. METHODS: We have created a computerized test for visual acuity assessment with optotypes arranged as those of printed logarithmic charts used in ophthalmic clinic. Ninety seven-year-old students, 8 normal adult volunteers and 10 patients from the Strabismus sector of the Federal University of Sao Paulo were evaluated by the same examiner and submitted to the visual acuity test through printed visual acuity logarithmic tumble "E" chart and the new computerized test at the same time. Written consent was obtained after clarification about the research project. RESULTS: Statistical analysis showed excellent correlation between the two methods (r>0.75) besides the slight trend of the computerized test to overestimate visual acuity when compared with the gold standard. Sensitivity of the computerized test was 100% (correctly identified 6 eyes with poor visual acuity) and specificity was 94%. CONCLUSION: The computerized test can be used as a new clinical tool for visual acuity screening of school-age children and it is fast, easy to perform and inexpensive, besides being more attractive for children. The method releases the examiner from the interpretation of the subject's answers and ensures the procedure's standardization even when more than one examiner performs the test. To better understand the effectiveness of this method for visual screening, one option would be to introduce it in elementary schools, after training the teachers to perform this test. PMID- 17273688 TI - [Study of ocular fungal microbiota in patients with Hansen's disease and in individuals who deal with them]. AB - PURPOSE: To study the conjunctival fungal flora of patients with leprosy who live in the colony hospital and of those who deal with "Hansen" patients. METHODS: Sixty-one eyes (61 patients) with Hansen's disease and twenty-five healthy eyes (25 individuals) of individuals who deal with patients were investigated. RESULTS: Conjunctival fungi growth occurred in 19.67% and 20% of the patients and healthy individuals, respectively. There was no significant difference (p<0.05) regarding fungi percentage of fungi isolated from the conjunctiva between both groups. Candida ssp was the most frequent fungus isolated from the conjunctiva of patients with Hansen's disease, whereas Penicillium spp was the most frequent fungus isolated from the group of people who deal with these patients. CONCLUSION: The most frequent yeast isolated from conjunctival samples of leprosy patients was Candida, which could be explained by cellular immunodeficiency of these patients, associated with dry eye and the prolonged use of antibiotics. PMID- 17273689 TI - Ultrasound biomicroscopy in the comparison of the anterior segment morphometry before and after pars plana vitrectomy. AB - PURPOSE: To determine if pars plana vitrectomy induces long-term changes in the anterior segment anatomy by means of ultrasound biomicroscopy. METHODS: A prospective case series study was undertaken of consecutive patients referred to a tertiary eye care centre for pars plana vitrectomy as the only procedure. Twenty eyes of 20 patients undergoing pars plana vitrectomy alone were studied by ultrasound biomicroscopy. Silicone oil or scleral buckle was not used in any of the included cases. The following morphometric parameters were compared before and after 3 months of surgery: anterior chamber depth, angle-opening distance at 500 microm from the scleral spur, trabecular-ciliary process distance, ciliary body thickness at 1, 2 and 3 millimeters from the scleral spur and measurement of the supraciliary space thickness, when fluid was detected. RESULTS: No statistically significant differences were found between the preoperative and the postoperative morphometric parameters. CONCLUSION: Uncomplicated pars plana vitrectomy does not induce any long-term change on anterior segment morphometry. Based on these findings, the normal long-term pattern to be expected after pars plana vitrectomy is the conservation of the preoperative morphometry. PMID- 17273690 TI - Patient education in glaucoma: what do patients know about glaucoma? AB - PURPOSE: To evaluate the knowledge glaucoma patients have about their disease and its treatment. METHODS: One hundred and eighty-three patients were interviewed at the Glaucoma Service of Wills Eye Hospital (Philadelphia, USA, Group 1) and 100 at the Glaucoma Service of University of Campinas (Campinas, Brazil, Group 2). An informal, relaxed atmosphere was created by the interviewer before asking a list of 18 open-ended questions. RESULTS: In Group 1, 44% of the 183 patients did not have an acceptable idea about what glaucoma is, 30% did not know the purpose of the medications they were taking, 47% were not aware of what was an average intraocular pressure, and 45% did not understand why visual fields were examined. In Group 2, 54% gave unsatisfactory answers to the question "What is glaucoma?", 54% did not know the purpose of the medications they were taking, 80% were not aware of what was an average intraocular pressure, and 94% did not understand why visual fields were examined (p<0.001). Linear regression analysis demonstrated that level of education was positively correlated to knowledge about glaucoma in both groups (r=0.65, p=0.001). CONCLUSION: This study showed that patients' knowledge about glaucoma varies greatly, and that in an urban, American setting, around one third of the patients have minimal understanding, whereas in an urban setting in Brazil around two thirds of patients were lacking basic information about glaucoma. Innovative and effective methods are needed to correct this situation. PMID- 17273691 TI - [Ophthalmologic findings in multiple handicapped patients]. AB - PURPOSE: To report the visual findings in patients with multiple handicaps. METHODS: Two hundred and seventy-four patients cared for at the Pediatric and Strabismus Ophthalmology Department of the "Fundacao Altino Ventura" - Brazilian National Health System, were examined from June to September 2004. Age varied from 0.1 to 20 years with a median of 5. RESULTS: The majority of the patients (61.3%) presented good visual acuity; however low visual acuity (< 20/80) was observed in 38.7% of the patients. Heterotropias were observed in 66 patients (24.0%); astigmatism (53.2%) and hyperopia (29.0%) were more frequent. CONCLUSION: Children with multiple handicaps need an early ophthalmologic diagnosis and treatment for better global development. The integration of a multidisciplinary team with pediatricians, pediatric ophthalmologists and specialists in low vision, may assure a better visual rehabilitation. PMID- 17273692 TI - [Pseudo-glaucoma in type VI mucopolysaccharidosis: case report]. AB - The authors report a case of a 19-year-old patient presenting with type VI mucopolysaccharidosis, diagnosed by genetic-clinical examination, demonstrating several systemic manifestations, including ocular disorders such as: corneal opacity, elevated intra-ocular pressure and increase of corneal thickness. The authors discuss the characteristic syndromic findings and the influence of corneal thickness associated with an increase in intraocular pressure leading to unnecessary antiglaucomatous treatment. PMID- 17273694 TI - [Intravitreal triamcinolone injection in the treatment of idiopathic juxtafoveal telangiectasis]. AB - Case report of one idiopathic juxtafoveal telangiectasis (IJT) 1A patient whose right eye was treated with a 4 mg intravitreal triamcinolone acetonide injection. The outcome was evaluated by visual acuity and optic coherence tomography. The visual acuity and the caliper retinal thickness before triamcinolone injection were respectively 20/100 and 569 microm, and 20/60 and 371 microm after three weeks and 20/100 and 614 microm after six week of follow-up. The stabilization of the vascular wall due to the intravitreal triamcinolone injection leads to a transitory improvement in vision and reduction in macular edema in the TJI 1A eyes. No permanent help by the photocoagulation could be shown. PMID- 17273693 TI - [Cogan's syndrome: ocular findings in an atypical case]. AB - Cogan's syndrome is an unusual multisystemic disease characterized by interstitial keratitis in association with vestibuloauditory dysfunction and possible irreversible deafness, classified into 2 clinical types: typical and atypical. There is disagreement in the literature about corneal disease in the atypical variety. A 32-year-old woman complaining of ocular hyperemia and ocular pain, photophobia and visual acuity loss in the right eye associated with sudden left hearing loss, vomiting, diarrhea, oliguria, oropharynx pain and fever. Previous history of similar disease in left eye and right hearing. There was intense conjunctival hyperemia, nodular scleritis, episcleritis, and circular infiltrates in the corneal stroma. The patient received pulse-therapy with methylprednisolone and cyclophosphamide. She exhibited significant ocular improvement but poor hearing results. The reported case may be a typical Cogan's syndrome (according to authors that assert the non-existence of corneal disease in the atypical type) with some findings characteristic of the atypical type or an atypical Cogan's syndrome (for those asserting that it is a corneal disease). Differential diagnosis is also discussed. PMID- 17273695 TI - [Posterior amorphous corneal dystrophy: case report]. AB - The purpose of this paper is to warn the ophthalmologist about the possibility of facing rare cases of corneal dystrophies. Clinical findings of a case of posterior amorphous dystrophy were correlated with refraction, topography, and ultrasound biomicroscopy. PMID- 17273697 TI - [Age-related macular degeneration: new perspectives]. AB - Age-related macular degeneration (ARMD) is a major source of legal blindness in individuals older than 50 years. Even though recent reports suggest that genetics plays an important role, its pathogenesis remains puzzling and the risk factors for its occurrence are not completely established. Vitamin and mineral supplementation reduced the risk of development of choroidal neovascularization (CNV) or progression to the most advanced stages of age-related macular degeneration. Photodynamic therapy (PDT) and antiangiogenic therapy have proved to be very useful for the treatment of choroidal neovascularization associated to age-related macular degeneration, by reducing the risk of vision loss and, occasionally, by a temporary improvement of vision. Only a small subset of patients may benefit from other treatment modalities, such as laser photocoagulation, surgical removal of choroidal neovascularization and transpupillary thermotherapy (TTT). Strategies to control and treat age-related macular degeneration may progress quickly as more is learned about its pathophysiology and the molecular events that contribute to the disease expression. PMID- 17273696 TI - [Choroid metastasis of testicular primary site: case report]. AB - Description of a male patient case, 22 years old, presenting visual acuity decrease in the left eye associated with the diagnosis of metastatic testicular tumor to lung and kidney. Evaluation of the evolution of a choroid lesion compatible with ocular metastasis of testis tumor through ophthalmologic and echographic examinations. There was resolution of the intraocular lesion together with lung radiologic improvement after chemotherapy during approximately 4 months of follow-up. In spite of the remission of the ocular lesion, the patient died due to complications of cerebral metastasis. Approached in the literature as rare, no report was found of a case of choroidal metastasis of a testicular site, this being, perhaps, its first description. PMID- 17273698 TI - [Sjogren's syndrome: diagnosis and treatment]. AB - Sjogren's syndrome is a systemic inflammatory autoimmune disease with worldwide distribution, responsible for considerable impact on the patient's quality of life. The aim of this article is to describe its main symptoms, the currently used different diagnostic criteria and the available treatment for the syndrome. PMID- 17273699 TI - [Visual stimulation in the child: the intervention from occupational therapy professionals]. PMID- 17273700 TI - Coleoptera associated with undisturbed cow pats in pastures in Southeastern Brazil. AB - Coleoptera associated to undisturbed cattle droppings in pastures present great diversity and abundance. Several species are of primary veterinary importance for they may act as natural enemies of pest insects that breed in this habitat. To survey the diversity and abundance of Coleoptera associated to undisturbed cattle droppings, four undisturbed cattle dung pats naturally dropped in pastures and 5 cm of the soil immediately beneath them were collected almost all weekly from April 1992 to April 1994 in a farm located in the vicinity of Sao Carlos, State of Sao Paulo, Southeastern Brazil. Beetles were collected from the pats both using Berlese funnels and by allowing the beetles to emerge for 30 to 40 days. A total of 24,332 specimens belonging to 13 beetle families and at least 66 species were identified. The most abundant and diverse families were Aphodiidae, Staphylinidae and Scarabaeidae. In general, the Coleoptera were more abundant in the warmer and wet period, from October to March, with a few exceptions. The importance of the beetles, both as horn fly natural enemies and as cattle dung decaying agents, is discussed. PMID- 17273702 TI - [Mites (Acari) associated to Myrtaceae in areas of Cerrado in the State of Sao Paulo with faunistic analysis of families Tarsonemidae and Phytoseiidae]. AB - The objective of this study was to determine and to analyse the diversity of mites on native Myrtaceae of the "Cerrado" vegetation type of the State of Sao Paulo, with particular attention to the families Phytoseiidae and Tarsonemidae. In the year 2000, mites were collected from Myrtaceae species in three "Cerrado" areas in the State of Sao Paulo. Samples of leaves, flowers and fruits were taken from three plant of each species in each site. Mites of 49 genera belonging to 14 families were found. Fourteen phytoseiid species of nine genera and 19 tarsonemid species of six genera were collected. The most abundant phytoseiids were Euseius citrifolius Denmark & Muma, Transeius bellottii (Moraes & Mesa) and Amblyseius acalyphus Denmark & Muma. The most abundant tarsonemids were Daidalotarsonemus tesselatus DeLeon, Daidalotarsonemus folisetae Lofego & Ochoa and Metatarsonemus megasolenidii Lofego & Ochoa. The highest indexes of diversity of phytoseiids and tarsonemids were observed in the fall; the lowest indexes were found in the winter for phytoseiids and in the spring for tarsonemids. Taking into consideration the total number of phytoseiids and tarsonemids collected in this work, the corresponding indexes of diversity (Shannon) were similar and close to 2.0. Different predatory mite species prevailed on distinct plant species, indicating the complementariness of the latter as reservoirs of the former. PMID- 17273701 TI - [Ant diversity (Hymenoptera: Formicidae) from capoes in Brazilian Pantanal: relationship between species richness and structural complexity]. AB - Species richness of epigeic ants was surveyed in forest islands named capoes of Brazilian Pantanal and related with their structural complexity. The ants were collected using pitfall traps in 28 capoes from Rio Negro Farm, in Aquidauana municipality, Mato-Grosso do Sul state, Brazil. The structural complexity of capoes was evaluated by measuring vegetation density and litter quantity near the pit-fall traps. Seventy-one species, distributed in 26 genera and seven sub families were found. Ectatomma edentatum Roger (Formicidae: Ectatomminae) and one species of Pheidole were the most frequent species. Species richness was positively correlated only with herbaceous vegetation density of capoes, supporting the idea that the increase in environmental heterogeneity diminishes species competition, allowing species co-occurrence. PMID- 17273703 TI - Effects of different protein concentrations on longevity and feeding behavior of two adult populations of Ceratitis capitata Wiedemann (Diptera: Tephritidae). AB - The effects of protein intake on two adult male and female populations of Ceratitis capitata Wiedemann were assessed. One population consisted of flies reared for twenty years in the laboratory (Lab-pop); the other population consisted both of flies reared in the laboratory for approximately fifteen years and of the periodically introduced wild flies (Hybrid-pop). Three diets were tested: a no-yeast diet and two diets containing yeast (protein source) at the concentrations 6.5 g or 1.5 g per 100 ml diet. The parameters analyzed were: adult longevity, diet intake with and without yeast, and discrimination threshold for yeast. Protein intake increased Lab-pop adult longevity and did not affect longevity of the Hybrid-pop. Longevity in each population was similar for males and females fed on the same diet. Food behavior were similar for male and female adults of both populations; all preferred diets containing protein (yeast). Males and females in both populations ingested similar amounts of each diet. The discrimination threshold for yeast was similar for all males (0.5 g yeast/100 ml diet); Lab-pop females were able to detect the presence of smaller quantities of yeast in their diet, thus having a higher discrimination capacity (0.4 g/100 ml diet) as compared to the Hybrid-pop females (0.6 g/ 100 ml diet). PMID- 17273704 TI - Seasonal population dynamics in Lucilia eximia (Wiedemann) (Diptera: Calliphoridae). AB - In this study the seasonal variation of fecundity, wing and tibia sizes were investigated in natural populations of Lucilia eximia (Wiedemann) as an attempt to determine the variations in life history of the species associated to seasonality. Specimens of L. eximia were monthly collected in Botucatu, Sao Paulo, Brazil, during two years and the adult females dissected to estimate fecundity. Body size was estimated by measuring wing and tibia. Fecundity and body size were seasonally analysed. A relatively constant temporal trajectory was found for fecundity, wing and tibia size over twenty-four months. Strong positive correlations between wing and tibia size, fecundity and wing and fecundity and tibia were observed. The maintenance of stable values in L. eximia indicates that it has suffered little seasonal influence over the period analysed. This result confirms the demographics and life history stable profile of the species in spite of seasonal climatic changes observed in the study area. PMID- 17273705 TI - Effect of relative humidity on emergence and on dispersal and regrouping of first instar Nezara viridula (L.) (Hemiptera: Pentatomidae). AB - Laboratory studies with 1st instar of southern green stink bug, Nezara viridula (L.) indicated that relative humidity (RH) greatly affected nymph emergence and survivorship up to the 2nd instar, reaching the maximum value (approximately 90%) with RH of > 80%. At 60% RH, 60% of the nymphs emerged and survived, while with 0% RH only approximately 15% of eggs hatched, and most nymphs died. Emerged nymphs from egg masses placed in plastic boxes with a gradient of humidity remained on egg shells for ca. one day. After this period, they dispersed and regrouped on top of shells 6.8 +/- 0.67 times, until they abandoned the shells toward the source of humidity, avoiding the water-saturated areas. Duration taken for each rearrangement (dispersal + regroup) increased with time, with a range of approximately 26 min to 44 min. The mean duration of the grouping behavior on egg shells after each rearrangement decreased from approximately 102 min (1st) to 24 min (6th and last grouping). The rearrangement behavior of 1st instars on top of egg shells apparently compensates for the water loss of nymphs. PMID- 17273706 TI - Modeling egg distribution of Tinocallis kahawaluokalani (Kirkaldy) (Hemiptera: Aphididae) on Lagerstroemia indica L. (Lythraceae). AB - This is the first record of winter eggs of the holocyclic monoeceous crapemyrtle aphid Tinocallis kahawaluokalani (Kirkaldy) on Lagerstroemia indica L., in Brazil. The shiny black eggs were observed since early autumn, laid on small folds and crevices of the branches. In order to evaluate and model the egg abundance and distribution, four branches from the cardinal points of 10 plants of two age groups, 5-10 and 20-30 years-old, were collected randomly and cut in eight segments of 10 cm and the number of eggs was registered, in the winter 2001. The eggs were laid mainly on the middle portion of the branch, from 40 cm to 60 cm from the apex on the older trees (54%) and on 30 cm to 60 cm on younger ones (58%). The data fit in a longitudinal regression model that expresses the tendency of the egg distribution on the branches. The number of eggs was greater on the 20-30 year-old plants (61%) than on younger ones (39%). The average number (+/- CI 95%) of eggs was 70.5 +/- 9.3 and 47.4 +/- 12.5, respectively, for the older and younger tree groups. There was no correlation between egg distribution and the cardinal positions of the branches. PMID- 17273707 TI - Sexual behavior of the navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae). AB - To get a better understanding of the mating behavior of the navel orangeworm, Amyelois transitella (Walker), we developed a robust laboratory colony derived from larvae collected in Bakersfield, California and fed on dried, roasted pistachio. In the lab at 25 degrees C, most of the mating activity was observed during the last hour of the scotophase and for the first 30 min of the photophase. Female calling was characterized by the abdomen being protruded between the wings with the distal segments perpendicular to the body and exposing a pheromone gland, as well as by continuous antennation. Males approached calling females from a short distance by displaying wing fanning and antennation. When a male antennated on a calling female's abdomen, she either accepted the male and lowered the abdomen, or walked away. The accepted male made a final approach parallel to the female's body, but after coupling he rotated 180 masculine with male and female remaining in a linear, abdomen-to-abdomen position for over 3 h in average. In a possible strategy to maximize the chances of mating, the sex ratio was significantly skewed towards males in the first two days of emergence. Almost 80% of mating took place in the first two days after adult emergence, with females mating only once. About 55% of males mated only once and approximately 40% of the observed males mated twice and 5% tree times. PMID- 17273708 TI - The dynamics of intraguild predation in Chrysomya albiceps Wied. (Diptera: Calliphoridae): interactions between instars and species under different abundances of food. AB - The pattern of larval interaction in blowflies confined with Chrysomya albiceps Wied. and C. rufifacies Maquart can be changed in response to the predatory behaviour of the two species to a contest-type process instead of the scramble competition that usually occurs in blowflies. Facultative predation is a frequent behaviour in C. albiceps and C. rufifacies that occurs as an alternative food source during the larval stage. In this study, we investigated the dynamics of intraguild predation by C. albiceps on other fly species in order to analyse interspecific and intraspecific survival in C. albiceps, C. megacephala and C. macellaria Fabricius. The experimental design of the study allowed us to evaluate how factors such as species, density and abundance of food influenced the survival of the calliphorid species. When C. albiceps was confined with C. megacephala or C. macellaria, only adults of C. albiceps survived at different larval densities and abundance of food. In addition, the survival of C. albiceps was higher in two-species experiments when compared to single species experiments. The implications of these results for the dynamics of C. albiceps were discussed. PMID- 17273709 TI - Laboratory environment effects on the reproduction and mortality of adult screwworm (Diptera: Calliphoridae). AB - The New World screwworm, Cochliomyia hominivorax Coquerel, is mass reared for screwworm eradication initiatives that use the sterile insect technique. New methods for rearing have helped to reduce the cost of the eradication program. We examined the effect and interaction of three temperatures (24.5, 29.5 and 34.5 degrees C), two diets (2% spray-dried blood plus 0.05% vitamins and corn syrup carrageenan) and three population densities (300, 400, and 500 flies/cage) on egg production, egg hatch, number of observable fertilized eggs, mortality (male and female) and ovarian development. The three population densities did not affect any of the parameters monitored. Using the protein diet increased egg production at all temperatures. Diet did not affect egg hatch or female mortality. Male mortality was significantly greater when fed the protein diet and reared at 24.5 degrees C and 34.5 degrees C. Egg hatch was significantly less when the flies were reared at 34.5 degrees C. When exposed to high temperatures (37 degrees C and 40 degrees C) egg production, egg hatch, fertility and mortality were adversely affected. At the higher temperatures, yolk did not adequately form during oogenesis. When compared to the normal rearing photoperiod (12 L:12 D), short photoperiod (1 L:23 D) increased egg production, egg hatch and fertility but lowered mortality. PMID- 17273710 TI - Nucleopolyhedrovirus: scanning electron microscopy technique. AB - A simplified methodology was developed to study the geometric form of multiple Bombyx mori Nucleopolyhedrovirus by scanning electron microscopy. The virus belongs to Baculoviridae family and was isolated from the silkworm Bombyx mori (L.) (Lepidoptera: Bombycidae). The polyhedra of Nucleopolyhedrovirus were obtained from the filtrate, inoculum and hemolymph of the silkworm experimentally infected with nuclear polyhedra. This material was placed on stubs, where a copper tape was previously adhered. After dry at room temperature the virus was covered with carbon and gold. Scanning electron microscopy analysis revealed a well defined morphology for the polyhedra of multiple Bombyx mori Nucleopolyhedrovirus, making possible the mathematical study that identified it as a truncated octahedron. The form of the polyhedron can present taxonomic value, once it is specific for each viral lineage. PMID- 17273711 TI - [The subgenus Megachile (Dasymegachile) Mitchell with special reference to the Argentine species (Hymenoptera: Megachilidae)]. AB - Seventeen species of Megachile (Dasymegachile) are recognized, twelve species from Chile, nine species from Argentina, three from Peru and one from Bolivia. Descriptions, illustrations, and keys for the identification for the Argentinean species are provided. The geographical distributions in Argentina are revised; M. cinerea and M. melanotricha are recorded for the first time from Argentina. Two species are also newly recorded from Chile. PMID- 17273712 TI - [Aquatic heteroptera from Mariana County, Minas Gerais, Brazil]. AB - In surveys carried out in lotic and lentic environments in Mariana County, Minas Gerais state, Brazil, 35 genera and 64 species of aquatic and semi-aquatic Heteroptera were recorded, distributed in 13 families. Thirty four species were collected in lentic environments, while in lotic environments 48 species were collected, some of them common to both environments. Nepomorpha presented the greatest number of species (45), markedly for the family Naucoridae, represented by 12 species. Among the 19 Gerromorpha species collected, eight were Veliidae and six were Gerridae. PMID- 17273713 TI - Evaluation of the RAPD profiles from different body parts of Euglossa pleosticta Dressler male bees (Hymenoptera: Apidae, Euglossina). AB - In the current literature, information is scarce on which part of the adult insect body is suitable for isolation of genomic DNA for genetic analysis based on DNA-markers. In this study, we evaluated RAPD profiles generated from total genomic DNA isolated from distinct body parts (head, legs, thorax + wings and abdomen) of 12 males of Euglossa pleosticta Dressler. From the total of bands analyzed, 9.0% did not show reproducibility. Percent variations of bands in each body segment were: 1.1% (head); 0.4% (legs); 0.8% (thorax/wings) and 6.7% (abdomen). The much higher variation (chi2(one sample) = 10.27; df = 1; P < 0.01) in the RAPD profiles obtained by using DNA isolated from abdomen of the euglossine males suggests that this body part of adult insects should be avoided in DNA extraction procedures. Conversely, the low variation among the RAPD profiles obtained from amplifications of genomic DNA extracted from head, legs and thorax/wings indicates that all these body parts of male bees are equally useful and secure for using in isolation and amplification procedures of total genomic DNA. PMID- 17273714 TI - Influence of parasitism by Chelonus insularis Cresson (Hymenoptera: Braconidae) on the susceptibility of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) to insecticides. AB - The egg-larval parasitoid Chelonus insularis Cresson is a key parasitoid of the fall armyworm Spodoptera frugiperda (J. E. Smith) during the second field generation in the upper Magdalena River Basin, Colombia. In spite of selection pressure, the higher susceptibility of the second generation fall armyworm larvae to insecticides, compared with that of the first generation, suggests that the parasitism may be responsible for the apparent difference in susceptibility. Parasitized and non-parasitized 2nd-instar larvae of the fall armyworm were tested for susceptibility to chlorpyriphos, methomyl, cypermethrin, and Bacillus thuringiensis in the laboratory, using the leaf dip test. Parasitized larvae were up to 3.93 times more susceptible to chlorpyriphos, 3.71 times to methomyl, and 14.11 times to cypermethrin than non-parasitized larvae. The least effect of parasitism on susceptibility was found for B. thuringiensis. We discuss the negative influence of synthetic insecticide on the parasitoid population dynamics and its impact on insecticide resistance. PMID- 17273715 TI - [Interaction between Acarophenax lacunatus (Cross & Krantz) (Prostigmata: Acarophenacidae) and Anisopteromalus calandrae (Howard) (Hymenoptera: Pteromalidae) on Rhyzopertha dominica (Fabricius) (Coleoptera: Bostrichidae)]. AB - The interaction between Acarophenax lacunatus (Cross & Krantz) and Anisopteromalus calandrae (Howard) may be a promising tool for the integrated pest management of stored grain insect pests. The objective of this study was to evaluate the compatibility of these two natural enemies on Rhyzopertha dominica (Fabricius). The experimental units were petri dishes (140 x 10 mm) containing 30 g of whole wheat grains (13% water content) infested with 20 adults of R. dominica. The treatments consisted of inoculation of A. lacunatus and A. calandrae, separately and associated, in eight replicates. Three inoculations of five adult females of the natural enemies were carried out in each petri dish at five, ten and fifteen days after the infestation of R. dominica. All treatments were stored during 60 days in environmental chamber at 30 +/- 1 degrees C, 60 +/- 5% relative humidity and 24 h scotophase. The smallest numbers of physogastric females of A. lacunatus and of adults of A. calandrae were obtained when the natural enemies were in association. The use of A. calandrae alone demonstrated a low instantaneous rate of increase (r(i)) of R. dominica and a high protection of the wheat grains. The association of A. calandrae with A. lacunatus led to the lowest number of immatures of R. dominica. These results demonstrate the importance of this interaction as a tool of for the integrated management of R. dominica in stored wheat grains. PMID- 17273716 TI - [Seasonal variation of immature stages of Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae) in Citrus sinensis orchards under two management systems]. AB - Phyllocnistis citrella Stainton is considered an important pest of citrus, causing both direct (reduction on the photosynthetic area) and indirect damage (facilitation of invasion by bacteria that cause citrus canker). The lack of information about the population dynamics of P. citrella, considering the cultivation systems and varieties grown in citrus orchards in Rio Grande do Sul, Brazil, motivated this study. It aimed to evaluate the seasonal variation of immature stages of P. citrella, from June 2002 to July 2003, in two orchards of Citrus sinensis, cv. 'Valencia', one maintained according to organic management principles and the other under conventional ones. Fortnightly samplings were carried out, being one shoot collected from each one of 27 randomly chosen plants. The leaves were analyzed for the presence of eggs, larvae, pupae and mines of P. citrella. Leafminer was recorded from October 2002 to April 2003 in the organic orchard, and from November 2002 to July 2003 in the conventional one. A relationship between population size and resource availability (young leaves) was observed. However, population establishment does not depend exclusively on the existence of resources, but also on suitable climatic conditions. This was evidenced by the absence of attacks on the first shooting, which began in late winter. Meteorological factors and resource availability as a whole explain about 64% and 53% of the observed variation in the population size of P. citrella, respectively in the organic and conventional orchards. PMID- 17273717 TI - [Effects of silicon acid and of acibenzolar-S-methyl on Schizaphis graminum (Rondani) (Hemiptera: Aphididae) in wheat plants]. AB - The objective of this work was to evaluate the effects of silicon acid and acibenzolar-S-methyl (ASM) on biology and behavior of the aphid (greenbug) in wheat plants. The experiment involved a 4 factorial (no silicon, silicon on leaf, silicon in the soil and silicon in the soil + on leaf), x 2 (with and without acibenzolar-S-methyl), in a completely randomized design. A preference test with chance of choice was set in blocks randomized, with 10 replications. Silicon acid was used at 1% and ASM at 0.5%. The treatments were evaluated by means of preference tests with chance of choice (adult aphids in leaf sections of wheat plants were counted), biological studies (length of pre-reproductive, reproductive and post-reproductive periods, mortality rate during the pre productive period, number of nymphs, longevity and population growth rate were determined) and colonization of aphids (number of adult aphids and nymphs were determined). In the preference test, plants that received ASM were not chosen by the aphids. The application of the silicon or ASM reduced significantly the number of nymphs, the population growth rate, the post-reproductive period and the longevity of the greenbug. A significant reduction of the number of aphids was observed during aphids colonization when ASM or silicon were applied. The addition of silicon acid, mostly in the soil, or of ASM is promising as a control method in the integrated management of aphid in wheat. PMID- 17273718 TI - [Stability of Brevipalpus phoenicis (Geijskes) (Acari: Tenuipalpidae) resistance to hexythiazox in citrus groves]. AB - The false spider mite, Brevipalpus phoenicis (Geijskes), is one the most important pests of the citrus groves and transmits the citrus leprosis virus. The acaricide hexythiazox has been widely used for controlling B. phoenicis in citrus groves. The resistance of this species to hexythiazox has already been detected at high frequencies at some locations. In order to implement a resistance management program, studies were undertaken to understand the stability of the resistance of B. phoenicis to hexythiazox by 1) comparing the life-history of susceptible (S) and resistant (R) strains under laboratory conditions, and 2) evaluating the dynamics of hexythiazox resistance in citrus field plots with low (< 20%) and high (> 60%) frequency of resistance, during two years. The frequencies of resistance were estimated with direct contact bioassays on eggs with discriminating concentration of 18 mg of hexythiazox/L of water. There were no significant differences between S and R strains, based on biological parameters evaluated to build fertility life tables. However, the resistance of B. phoenicis to hexythiazox was unstable under field conditions; that is, significant reductions in the frequency of resistance were observed in the absence of selection pressure, either in citrus field plots with low or high frequency of resistance. Therefore, the instability of B. phoenicis resistance to hexythiazox can be exploited in resistance management programs. PMID- 17273719 TI - Biological activity of Bacillus thuringiensis strains against larvae of the blowfly Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae). AB - Different strains of Bacillus thuringiensis Berliner were proved to be a powerful biologic insecticide against larvae of several insect orders. Due to the epidemiological importance of blowflies of the Chrysomya Robineau-Desvoidy genus in the production of secondary cutaneous myiasis and mechanic transmission of pathogenic agents, the performance of two strains of B. thuringiensis (LFB FIOCRUZ 907 and LFB-FIOCRUZ 856) was tested against larvae of Chrysomya putoria (Wiedemann). The LFB-FIOCRUZ 907 strain was tested in four different concentrations, added to the diet; the LFB-FIOCRUZ 856 strain was tested in three concentrations. C. putoria larvae showed sensibility to the treatment with the LFB-FIOCRUZ 907 strain at the tested concentrations. The higher concentration presented the best efficiency, causing higher mortality and reducing larval weight and adult emergence more intensely. The LFB-FIOCRUZ 856 strain showed low toxicity, slightly reducing emergence time of adults at 326 mg/25 g concentration and larval weight at 326 mg/25 g and 86 mg/25 g concentrations. PMID- 17273720 TI - [Biology and thermal exigency of Aedes aegypti (L.) (Diptera: Culicidae) from four bioclimatic localities of Paraiba]. AB - The present work aimed at estimating the thermal requirements for the development and the number of generations per year of Aedes aegypti (L.) under natural conditions. The life cycle of A. aegypti populations was studied at constant temperatures of 18, 22, 26, 30 and 34 degrees C, and 12 h photophase. The development period, egg viability and larval and pupal survival were evaluated daily as well as adult longevity and fecundity. The low threshold temperature of development (Tb) and the thermal constant (K) were determined. The number of generations per year in laboratory and field were also estimated. The favorable temperature to A. aegypti development is between 21 degrees C and 29 degrees C, and to longevity and fecundity is between 22 degrees C and 30 degrees C. The egg to adult basal temperature, thermal constant and the number of generations in field were, in order, 9.5, 8.5, 3.4, 7.1, 13.5 degrees C; 244.5, 273.9, 298.5, 280.9 and 161.8 degree-days; and 21.9, 23.8, 24.2, 21.1 and 22.1 generations in populations from Boqueirao, Brejo dos Santos, Campina Grande, Itaporanga and Remigio. PMID- 17273721 TI - [First record of Platycorypha nigrivirga Burckhardt (Hemiptera: Psylloidea), in Tipuana tipu (Benth.), from Brazil]. AB - The occurrence of Platycorypha nigrivirga Burckhardt (Hemiptera: Psyllidae, Acizzinae), is reported for the first time, in Brazil. The psyllid was observed causing injuries on leaves and shoots of Tipuana tipu (Benth.), in urban areas of Parana State. P. nigrivirga are tiny sap-sucking insects that feed on phloem and cause curling, stains and fall of leaves. The excrements of these insects accumulate on the leaves propitiating fungus growth on the leaves, or they fall in great amount on the cars dirtying them as if they were sparkling of white and sticky ink. PMID- 17273722 TI - Occurrence of Platypus mutatus Chapuis (Coleoptera: Platypodidae) in a brazilwood experimental plantation in Southeastern Brazil. AB - The hardwood of Caesalpinia echinata Lam. (brazilwood, Pernambuco, ibirapitanga) is currently the most profitable material used for violin bow due to the unique vibrational properties and dimensional stability. Although this species is resistant to the wood decay caused by termites and rot fungi, an experimental plantation in Southeastern Brazil has been attacked by the ambrosia beetle Platypus mutatus Chapuis (= Megaplatypus mutatus and P. sulcatus). This species invaded ca. 3% of the individuals, mainly in the central part of the plantation. Infestation by larvae and adults was higher during the dry season (winter) when compared to the rainy period (spring and summer). PMID- 17273723 TI - Occurrence of Aglae caerulea Lepeletier & Serville (Hymenoptera: Apidae: Euglossini) in the Parque Nacional da Chapada dos Guimaraes, Mato Grosso State, Brazil. AB - In a study conducted in the gallery forest of the Vale doVeu de Noiva in the Parque Nacional da Chapada dos Guimaraes, Mato Grosso state, chemical baits were used to attract and sample male orchid bees. From September 2003 to July 2005, male euglossine bees were captured monthly, from 8:00 a.m. to 4:00 p.m. as they arrived at the baits. Of the 264 males captured, eight males belonged to Aglae caerulea Lepeletier & Serville, a cleptoparasitic euglossine species that presumably occurred only in the Amazon basin. Therefore, the occurrence of A. caerulea in this study area extends its geographical distribution range by approximately 2,400 km southwards in South America, as it is now recorded in both the Amazon and Platina basins. PMID- 17273724 TI - Navia, a replacement generic name for Euterpia Navia & Flechtmann (Prostigmata: Eriophyoidea: Eriophyidae). AB - Navia nom. nov. is proposed for Euterpia Navia & Flechtmann, 2005 (Prostigmata: Eriophyoidea), preoccupied by Euterpia Bondar, 1942 (Insecta: Coleoptera: Curculionidae). PMID- 17273725 TI - Current advances in the basic research and clinical management of sinonasal inverted papilloma (review). AB - Inverted papilloma (IP) is a benign sinonasal lesion that has a known propensity for recurrence, local aggressiveness and an association with transformation to squamous cell carcinoma. Due to the high rate of recurrence, association with malignancy and a tendency of multicentricity, the surgical approaches to treatment are controversial. Over the years there has been a slow evolution from aggressive (en bloc) resection by lateral rhinotomy to endoscopic techniques. This progress corresponds to the advances that have been made in endoscopic sinus surgery over the past 15 years. Technological advances have allowed the detection of sinonasal IP before its extension beyond the sinonasal region, thus enabling minimally invasive techniques to be used in the treatment of selected cases of IP. Differences in recurrence rates were not observed for endoscopic management as compared with lateral rhinotomy or sublabial degloving approaches. In terms of aetiology there is certain evidence that the presence of HPV in IP could be predictive of malignant transformation. Although IPs are monoclonal proliferations, they do not fit the profile of a prototypic precursor lesion. In contrast, an increased EGFR and TGF-alpha expression is associated with early events in IP carcinogenesis. Parameters such as hyperkeratosis, squamous epithelial hyperplasia and a high mitotic index are negative prognostic indicators, which could be useful in the future follow-up of patients with IP. Present literature should encourage us to recommend the use of a uniformly accepted staging system. The propensity for delayed recurrences and the maximal 13% incidence of malignant transformation mandates careful, long-term follow-up. PMID- 17273726 TI - Expression of factors involved in regulation of DNA mismatch repair- and apoptosis pathways in ovarian cancer patients. AB - A major obstacle in treatment of ovarian cancer is intrinsic or acquired drug resistance causing failure of chemotherapy followed by a poor clinical outcome. Drug resistance of ovarian carcinoma can be caused by dysregulation of cellular factors involved in regulation of apoptosis and DNA repair pathways. In this study, 73 ovarian carcinoma specimens obtained before and after chemotherapy were analysed by immunohistochemistry for expression of seven proteins playing an important role in regulation of DNA mismatch repair and apoptosis. The prognostic significance of these proteins in the meaning of overall and progression-free survival was evaluated in univariate and multivariate analysis. Bcl-xL, hMSH2, caspase-3, p21 and p53 displayed prognostic importance in univariate analysis. Furthermore, it was demonstrated that caspase-3 and p21 were also independent prognostic markers for both, overall and progression-free survival. In conclusion, these data indicate that analysis of proteins involved in DNA mismatch repair and apoptosis can be useful for prediction of clinical outcome in ovarian carcinoma patients. PMID- 17273727 TI - Snail plays a key role in E-cadherin-preserved esophageal squamous cell carcinoma. AB - Snail is a zinc-finger transcription factor that triggers the epithelial mesenchymal transition (EMT) by directly repressing E-cadherin expression. However, the relationship between E-cadherin and Snail expression remains unclear in esophageal squamous cell carcinoma (ESCC). The purpose of the present study was to evaluate the clinical significance of E-cadherin and Snail expression in ESCC. Immunohistochemistry was used to investigate the expression of E-cadherin and Snail proteins in 194 patients with ESCC. The relationship between expression of these proteins and clinicopathological factors was analyzed, and the usefulness of Snail in disease prognosis was evaluated in relation to E-cadherin expression. E-cadherin expression was preserved in 41.2% of tumors, and Snail expression was confirmed in 61.7%. Tumors with reduced E-cadherin expression invaded deeper (P<0.0001), had more lymph node metastasis (P<0.0001) and had more lymphatic invasion (P=0.0011) than tumors with preserved expression. Tumors that were positive for Snail expression invaded deeper (P=0.0385), had more distant lymph node metastasis (pM) (P=0.0051) and had a more advanced stage (P=0.0044) than those that were negative for Snail expression. Snail expression was not significantly correlated with reduced E-cadherin expression. Patients with reduced E-cadherin expression or positive Snail expression had poor clinical outcomes. In the preserved E-cadherin group, overall survival rate was better in patients with negative Snail expression than in those with positive Snail expression (P=0.035). Snail appears to play a key role in preserved E-cadherin expression. Further studies on other molecules in the pathways related to reduced E-cadherin expression in ESCC from the view-point of EMT are necessary. PMID- 17273729 TI - Frequent immunoexpression of TGF-beta1, FGF-2 and BMP-2 in fibroblast-like cells in osteofibrous dysplasia. AB - Osteofibrous dysplasia (OFD) and fibrous dysplasia (FD) are both benign bone lesions which comprise the proliferation of fibroblast-like cells with bone formation, and these fibroblast-like cells have the phenotype of osteoprogenitor cells. The roentgenograph of OFD shows a heterogeneous osteolytic lesion with surrounding osteosclerosis, whereas FD is typically characterized by a rather homogeneous osteolytic lesion, or 'ground-glass appearance', with a smaller amount of surrounding osteosclerosis. Growth factors of transforming growth factor-beta1 (TGF-beta1), fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) modulate bone differentiation. Expression of these growth factors was examined in the fibroblast-like cells of 16 cases of OFD and 16 cases of FD, immunohistochemically. TGF-beta1 in fibroblast-like cells was frequently expressed both in the OFD (16/16) and the FD (15/16) cases. The frequency of FGF-2 (16/16) expression and BMP-2 (13/16) expression in the fibroblast-like cells of OFD was higher than that of those [FGF-2 (8/16) and BMP 2 (6/16)] in the fibroblast-like cells of FD, with a statistical significance. These results seem to suggest that fibroblast-like cells of OFD have greater bone forming ability than those of FD, and may explain the roentgenographic difference between OFD and FD and a difference in the nature of fibroblast-like cells between these two types of lesions. PMID- 17273728 TI - Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors. AB - Evaluation of the relationship between clinicopathological and immunohistochemical risk factors for liver metastasis, including CD10 expression, is meaningful in colorectal carcinoma (CRC). The purpose of the present study was to clarify what kind of risk factors are significant and independent factors for the development of liver metastasis in CRC. Sixty cases of advanced CRC with synchronous liver metastasis and sixty cases of advanced CRC without liver metastasis at least 5 years after resection of the primary CRC were randomly selected. We analysed the clinicopathological factors and the expression of four biological factors, CD44, transforming growth factor alpha (TGF-alpha), vascular endothelial growth factor (VEGF) and CD10, by immunohistochemistry. Univariate analysis revealed that the incidence of vascular invasion, the incidence of lymph node metastasis and the expression of CD44, TGF-alpha, VEGF and CD10 were all significantly higher in the cases of CRC with liver metastasis than in cases of non-metastatic CRC. Logistic regression analysis showed that lymph node metastasis, the expression of CD10 and the expression of VEGF were significant factors and independent of the other variables. If all three markers are positive, the probability of liver metastasis becomes 92.7%. In this study, lymph node metastasis, CD10 and VEGF were all found to be significant risk factors for the development of liver metastasis in the cases of CRC. These risk factors according to multivariate analysis are candidate markers for predicting the development of liver metastasis. PMID- 17273730 TI - Photosensitizer effect of curcumin on UVB-irradiated HaCaT cells through activation of caspase pathways. AB - Photodynamic therapy (PDT) using photosensitizer can induce diverse cellular responses, including apoptosis. Recently, it has been reported that PDT using methylaminolaevulinate may be effective in basal cell carcinoma. However, it is largely unknown whether PDT using a natural product such as curcumin can induce apoptosis in skin cancer. In this study, to confirm the photodynamic effect of curcumin, we investigated the synergistic effect of the combination of UVB with curcumin on apoptotic cell death in HaCaT cells and molecular mechanisms underlying apoptosis. Our data showed that HaCaT cells were markedly undergoing apoptosis, evidenced by DNA laddering, by combination of UVB with curcumin, compared to UVB or curcumin alone. Furthermore, combination of UVB irradiation with curcumin synergistically induces apoptotic cell death in HaCaT cells through activation of caspase-8, and -3 as well as caspase-9 activation followed by release of cytochrome c. Thus, our data indicate that curcumin may be a promising photosensitizer used in PDT to induce apoptosis in skin cancer cells. PMID- 17273732 TI - SIAH1 causes growth arrest and apoptosis in hepatoma cells through beta-catenin degradation-dependent and -independent mechanisms. AB - We have previously shown that expression of SIAH1 is frequently down-regulated in HCCs and associated with their advanced stages. It has been shown that SIAH1 functions in the phosphorylation-independent degradation of beta-catenin and induces apoptosis and growth arrest. To examine if the effects of SIAH1 overexpression depend on the altered beta-catenin signaling pathway, we transferred the SIAH1 gene into three hepatoma cell lines with different genetic backgrounds: HepG2 (mutant beta-catenin), SNU475 (mutant AXIN1), and Huh7 cells (wild type beta-catenin and AXIN1). SIAH1 significantly decreased aberrant beta catenin signal in HepG2 and SNU475 cells and induced growth arrest and apoptosis. However, SIAH1 also induced apoptosis in Huh7 cells, which retained a normal membranous distribution pattern of beta-catenin. Immunoblotting study demonstrated that SIAH1 also reduces the amount of PEG10 protein, which is known to be frequently overexpressed in HCC and to promote cell proliferation. These data suggest that PEG10 is another target protein of SIAH1 to induce apoptosis in hepatoma cells. Our results should lead to a better understanding of the relationship between deregulation of beta-catenin signals and hepatocarcinogenesis. Further investigations into the mechanisms by which SIAH1 promotes apoptosis and suppresses cell growth should also allow for the discovery of new therapeutic strategies. PMID- 17273731 TI - A diagnostic evaluation of serum human telomerase reverse transcriptase mRNA as a novel tumor marker for gynecologic malignancies. AB - Human telomerase reverse transcriptase (hTERT) and epidermal growth factor receptor (EGFR) play an important role in many cancers including gynecological cancers. We previously reported the usefulness of a quantitative highly sensitive detection method for hTERT mRNA in the serum of cancer patients. By this method, we attempted to elucidate the diagnostic evaluation of serum hTERT mRNA for gynecologic malignancies. In 174 female patients with gynecological lesions (47 with ovarian lesions, 63 with uterine lesions, 2 with malignancies in other gynecological lesions, and 62 benign lesions) and 20 healthy individuals, we measured serum hTERT mRNA and EGFR mRNA by using the newly developed real-time quantitative RT-PCR. We examined their sensitivity and specificity in cancer diagnosis, clinical significance in comparison with conventional tumor markers, and their correlations with the clinical parameters by using multivariate analyses. Serum hTERT mRNA showed higher values in patients with gynecologic cancers than in those with benign diseases and healthy individuals. The hTERT mRNA level independently correlated with the presence of cancers (P=0.004 for both ovarian and uterine cancer) and clinical stage (P<0.001). The sensitivity and specificity of hTERT mRNA in cancer diagnosis was 74.4% and 74.1%, respectively. The hTERT mRNA level showed a significant correlation with CA125 by Pearson's relative test (P=0.035) and with histological findings in ovarian cancer by the Friedman test (P<0.004). EGFR mRNA did not display any differences between the diseases. hTERT mRNA is useful for diagnosing gynecologic cancer and is superior to conventional tumor markers. Therefore, serum hTERT mRNA is a novel and available biomarker for gynecologic malignancies. PMID- 17273734 TI - Genetic polymorphism and gene expression of microsomal epoxide hydrolase in non small cell lung cancer. AB - Genetic polymorphisms of microsomal epoxide hydrolase (mEH) have been associated with increased risk of lung cancer. However, expression of mEH and its clinical significance in non-small cell lung cancer (NSCLC) have not been investigated. In this study we investigated the expression and genetic polymorphism of mEH in non small cell lung cancer (NSCLC) patients. Genetic polymorphism was determined by restriction fragment length polymorphism of polymerase chain reaction (PCR) products. The allelic expression pattern as well as expression level of mEH were determined by reverse transcription-PCR (RT-PCR), cDNA sequencing, sequence alignment, immunoblotting and immunohistochemistry. Genotype distributions of mEH in Taiwan's NSCLC patients were 44.4% of 340TAC/340TAC, 48.6% of 340TAC/340CAC, and 7.0% of 340CAC/340CAC in exon 3, and 80.6% of 418CAT/418CAT, 19.4% of 418CAT/418CGT and 0% of 418CGT/418CGT in exon 4. Of the 72 NSCLC biopsies analyzed, mEH was expressed in 60 (83%) surgical specimens, and the major allelic expression pattern was fast type (Tyr113) in exon 3 (90.3%) and slow type (His139) in exon 4 (100%). Immunohistochemical staining showed that mEH was expressed in 326 of 423 (77.0%) tumor (lung tissue) specimens and in 48 of 93 (51.6%) metastatic lymph nodes. A significant difference in patient survival was found when mEH expression and adriamycin-containing chemotherapy were used to group patients (p=0.0167). In conclusion, with the combination of fast type (Tyr113) and slow type (His139), the mEH enzyme expressed in most NSCLC patients may have intermediate activity. Our findings indicate that with respect to cancer risk and disease progression, the expression level of mEH is as important as genetic polymorphism. In addition, mEH expression in NSCLC could be involved in drug resistance and prognosis of patients. PMID- 17273733 TI - Co-expression of aFGF and FGFR-1 is predictive of a poor prognosis in patients with esophageal squamous cell carcinoma. AB - Overexpression of aFGF, bFGF and FGFR-1 has been reported in various cancers, and it has been suggested that it may be a poor prognostic factor in cases with solid tumors. Therefore, we attempted to determine whether overexpression of aFGF, bFGF and FGFR-1 might also be a poor prognostic factor in patients with esophageal squamous cell carcinoma, and examined the expression of aFGF, bFGF and FGFR-1 in esophageal cancer tissue specimens to clarify their clinical significance. Seventy-nine patients with squamous cell carcinoma of the esophagus who underwent resection at the Department of Surgery, Keio University Hospital, were enrolled as the subjects of this study. None of the patients had received any previous treatment. Formalin-fixed and paraffin-embedded sections of esophageal cancer tissue were stained by immunohistochemical methods and examined for expression of the angiogenetic factors and their receptors, and also to determine the microvascular density (MVD). We examined the correlations between the expression of aFGF, bFGF and FGFR-1, and the MVD, clinicopathological background factors and survival of the patients by conducting statistical analyses of the data. The results revealed that positive aFGF expression was associated with a larger tumor area (p=0.009), and co-expression of both aFGF and FGFR-1 was associated with a larger tumor area (p=0.01) and poorer prognosis (p=0.04). There were positive correlations between the expression of aFGF and FGFR-1 (p<0.0001), and between those of bFGF and FGFR-1 (p=0.04). aFGF may promote proliferation of esophageal cancer cells in an angiogenesis-independent and autocrine manner, and may contribute to rapid growth of esophageal cancer on recurrence after esophageal resection. PMID- 17273735 TI - Modification of gene expression by melatonin in UVB-irradiated HaCaT keratinocyte cell lines using a cDNA microarray. AB - Excessive ultraviolet B (UVB) irradiation causes apoptotic cell death or induction of tumors in skin. Melatonin is a promising antioxidant and direct radical scavenger. Recently, it was reported that melatonin increases the survival of ultraviolet-B (UVB)-irradiated HaCaT keratinocyte cell lines. However, the precise molecular mechanisms underlying protective effect of melatonin on UVB damage are largely unknown. In this study, to gain more insight into the molecular mechanisms involved in melatonin-induced cell survival on UVB irradiated HaCaT keratinocytes, we performed cDNA microarray analysis. HaCaT keratinocytes were incubated without or with melatonin at 100 nm for 30 min prior to UVB irradiation at 100 mJ/cm(2), and total RNA was isolated. Our data showed that the expression of apoptosis regulator genes (apoptosis related protein-3, apoptotic chromatin condensation inducer in the nucleus), cancer related genes (tumor suppressor deleted in oral cancer-related 1), cell cycle regulator (cyclin dependent kinase 2 interacting protein), enzymes (glutathione peroxidase 1, ubiquitin-conjugating enzyme E2M), and signal transducer genes [fibroblast growth factor (acidic) intracellular binding protein, transforming growth factor beta stimulated protein TSC-22] were decreased by melatonin treatment in the UVB irradiated HaCaT keratinocyte cell lines, compared to that of UVB-irradiated HaCaT cells without melatonin. Thus, findings of the present study demonstrate that melatonin modulates the expression of apoptosis related genes in UVB irradiated HaCaT cells, resulting in increasing cell survival, thereby suggesting that melatonin may be used as a promising sunscreen substance to reduce cell death of keratinocytes after excessive UVB irradiation. PMID- 17273736 TI - Cytological findings of pre-invasive bronchial lesions detected by light-induced fluorescence endoscopy in a lung cancer screening system. AB - Lung cancer is a global epidemic and the number one cause of death among all cancers, with a very high morbidity. A new strategy for the treatment of lung cancer is the detection and eradication of pre-invasive bronchial lesions before they become invasive carcinomas. We conducted a detailed investigation into the use of fluorescence bronchoscopy in the detection of pre-invasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. We also studied the distinctive cytological findings in the sputum specimens corresponding to the pre-invasive bronchial lesions. Sputum examinations were performed by mass screening a high-risk group of participants. From 1997 to 1999, 61 participants with sputum cytology suspicious or positive for malignancy were referred to our institute, and were examined with both white-light and fluorescence bronchoscopy. For the cytological findings, the collection of sputum was performed in the early morning. Conventional white-light examinations were first performed, and areas with abnormal findings were recorded for subsequent biopsy. Fluorescence bronchoscopy examinations were then carried out. Biopsy specimens for a pathological examination were taken from all the suspicious or abnormal areas discovered by the white-light bronchoscopy, or fluorescence bronchoscopy examination, or both. The laser-induced fluorescence bronchoscopic examination showed a high sensitivity for invasive carcinoma, carcinoma in situ, as well as severe, moderate, and mild dysplasia. In the sputum cytological findings, a thickened cytoplasm and slight hyperchromasia were frequently observed in the mild dysplasias compared with the squamous cells without atypia. Hyperchromasia and an Orange G (OG)-philic cytoplasm of squamous cells were frequently observed in the moderate compared with the mild dysplasias. A thickened cytoplasm, a nuclear pleomorphism, a thickened nuclear rim, a coarse chromatin, an uneven chromatin distribution, and an OG-philic cytoplasm were frequently observed in the carcinomas in situ and severe dysplasias compared with the moderate dysplasias. We found that the use of fluorescence bronchoscopy in addition to conventional white-light examination can enhance the detection and localization of pre-invasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. Sputum cytology is therefore a potential approach to diagnosing pre-invasive bronchial lesions. PMID- 17273737 TI - Leydig cell tumors of the testis: a molecular-cytogenetic study based on a large series of patients. AB - The genetic features of the uncommon Leydig cell tumors (LCT) are largely unknown. Consequently, it is of great importance to elucidate the pathogenesis of testicular germ cell tumors by cytogenetic and molecular biological investigations. The purpose of the present study was the examination of cytogenetic features of these tumors in a large series of LCT. It comprised formalin-fixed, paraffin-embedded tissue samples from 25 LCT to analyze the chromosomal constitution using comparative genomic hybridization (CGH). In most of the studied cases, the aberrant cell population was additionally defined by interphase fluorescence in situ hybridization (I-FISH). Our molecular-cytogenetic study indicates chromosomal imbalances in the majority of our cases (21/25, 84%). The most frequent findings were gain of chromosome X, 19 or 19p and loss on chromosome 8 and 16. PMID- 17273738 TI - Immunohistochemical expression of heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) as an angiogenic factor in head and neck tumorigenesis. AB - Heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) is a secreted protein that releases immobilized fibroblast growth factor-2 (FGF-2) from the extracellular matrix and plays a critical role in FGF bioactivation. In the present study co-localization of FGF-2 and HBp17/FGFBP-1 was observed in oral tissues including normal mucosa, hyperplasia, dysplasia of different degrees and oral squamous cell carcinoma (OSCC). The expression score for HBp17/FGFBP-1, FGF-2 as well as vascular endothelial growth factor A (VEGF-A) became higher with the severity of epithelial dysplasia and was highest in severe dysplasia. The expression of HBp17/FGFBP-1, FGF-2 and VEGF-A showed significant association with microvessel density, but no correlation with TNM stages or OSCC recurrence interval. Our results demonstrated that HBp17/FGFBP-1, like VEGF-A and FGF-2, might also promote the induction of tumor angiogenesis. The strongest expression of angiogenic factors in severe dysplasia suggests a potential point for targeting novel anti-angiogenic therapeutic strategies. PMID- 17273739 TI - Lidamycin induces marked G2 cell cycle arrest in human colon carcinoma HT-29 cells through activation of p38 MAPK pathway. AB - Lidamycin (LDM), a member of the enediyne antibiotic family, is presently undergoing phase I clinical trials in P.R. China. In this study, we investigated the mechanisms of LDM-induced cell cycle arrest in order to support its use in clinical cancer therapy. Using human colon carcinoma HT-29 cells, we observed that LDM induced G2 cell cycle arrest in a time- and dose-dependent manner. LDM induced G2 arrest was associated with increasing phosphorylation of Chk1, Chk2, Cdc25C, Cdc2 and expression of Cdc2 and cyclin B1. In addition, cytoplasmic localization of cyclin B1 was also involved in LDM-induced G2 arrest. Moreover, we found that p38 MAPK pathway contributed to LDM-induced G2 arrest. Inhibition of p38 MAPK by its inhibitor SB203580 not only attenuated LDM-induced G2 arrest but also potentiated LDM-induced apoptosis, which was accompanied by decreasing phosphorylation of Cdc2 and increasing expression of FasL and phosphorylation of JNK. Finally, we demonstrated that cells at G1 phase were more sensitive to LDM. Together, our findings suggest that p38 MAPK signaling pathway is involved in LDM induced G2 arrest, at least partly, and a combination of LDM with p38 MAPK inhibitor may represent a new strategy for human colon cancer therapy. PMID- 17273740 TI - BNIPL-2 promotes the invasion and metastasis of human hepatocellular carcinoma cells. AB - Enhanced cell migration and invasion play key roles in cancer metastasis. However, the molecules involved in this process are not fully understood. In this study, a full-length human BNIPL-2 (Bcl-2/adenovirus E1B 19 kDa interacting protein 2 like-2) cDNA was transfected into human hepatocellular carcinoma cells with low metastatic potential (MHCC97-L). The in vitro and in vivo effects of BNIPL-2 on cell invasion and metastasis were examined. In vitro analysis showed that the overexpression of BNIPL-2 increases cell invasion and promotes cell migration. The rates of intrahepatic and pulmonary metastasis in nude mice were also increased. Cdc42 activation assays and immunoblot analysis indicated that the activation of Cdc42 and the upregulation of CD44 were involved in the metastasis of cancer cells. The overexpression of BNIPL-2 promotes the invasion and metastasis of MHCC97-L cells. Thus, BNIPL-2 is a gene related with cancer metastasis. PMID- 17273741 TI - S-phase reduction in T47D human breast cancer epithelial cells induced by an S100P antisense-retroviral construct. AB - S100P is expressed in several malignant neoplasms. It was previously demonstrated that S100P is involved in the very early stages of breast carcinogenesis. In the present study we used a retrovirus-mediated transfer of antisense-S100P in order to check whether the decrease in expression of this protein could lead to alterations in the cell cycle of epithelial cells of human breast cancer. The T47D breast carcinoma cell line, a human breast epithelial cell that expresses high levels of S100P, was a tool used in this study to investigate the alteration in cell cycle induced by a retrovirus-mediated transfer of antisense-S100P. First we used the real-time PCR technique to quantify the gene expression. The results showed a reduction of 63% of expression within the T47D-S100P-A/S infected population compared with control T47D-LXSN clones. To determine the impact of the S100P antisense technique on protein expression in T47D cells, we performed immunofluorescence staining and analyzed the resulting images using a confocal microscope. The images showed much less pronounced antibody marking of the S100P protein in the T47D-S100P-A/S compared with control cells. To evaluate whether the antisense approach caused any alteration in the cell cycle, we concluded the study with flow cytometric analysis of the cell distribution. Our findings indicated that, in our model, S100P-antisense cells showed a 23% reduction of cells at the S-phase. Using transduction techniques with an S100P antisense retroviral construct we were able to demonstrate a significant reduction in S phase of the T47D cell cycle. To the best of our knowledge, this is the first time that an antisense approach has been used against S100P mRNA in breast cancer epithelial cells. The results showed here seem to further classify S100P as a protein that might be involved in the cell cycle imbalance observed during breast carcinogenesis. PMID- 17273742 TI - Preventive effects of glycyrrhizin on estrogen-related endometrial carcinogenesis in mice. AB - We have previously reported on the inhibitory effect of Glycyrrhizae radix (Gl radix) on mouse endometrial carcinogenesis. The present study was performed to clarify the effects of Gl radix and glycyrrhizin (GL), the main part of Gl radix, on estradiol (E2)-related endometrial carcinogenesis. Both Gl radix and GL exerted a significant decrease in the COX-2, IL-1alpha and TNF-alpha mRNA expressions. GL generated a significant decrease in the incidence of endometrial adenocarcinoma. Accordingly, the preventive effects of Gl radix may be attributable to GL, thus being related with the suppression of COX-2, IL-1alpha and TNF-alpha. Gl radix and GL could therefore be a promising formula for the chemoprevention of human endometrial cancer. PMID- 17273743 TI - Clinical significance of RCAS1 as a biomarker of ovarian cancer. AB - Expression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is associated with advanced disease of various malignancies including ovarian cancer. Proteolytic cleavage of RCAS1 at extracellular domains (ectodomain shedding) yields soluble RCAS1. Although RCAS1 can induce apoptosis in normal peripheral lymphocytes, its clinical significance and biologic function in ovarian cancer patients are unclear. Here, we evaluated serum RCAS1 concentrations to clarify its clinical significance and biologic activity in ovarian cancer. Via ELISA, we measured serum RCAS1 concentrations in samples from 75 healthy blood donors and 97 patients, 36 with ovarian benign tumor and 61 with ovarian cancer. We correlated via statistical means the RCAS1 values with patients' clinicopathologic variables. We assessed inhibition of growth of K562 cells, which express the putative RCAS1 receptor, via WST-1 assay of serum samples to clarify RCAS1's biologic activity. Ovarian cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors and ovarian tumor patients (P<0.05). RCAS1 level was significantly different according to histologic subtype for both ovarian tumor and cancer patients (P=0.0266 and 0.0074, respectively). RCAS1 values were also significantly associated with response to treatment (P<0.001). The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1 (P=0.0074). RCAS1 may be a biomarker of ovarian cancer by virtue of its ability to predict results of treatment and inhibit immune cell growth. PMID- 17273744 TI - Kinesin superfamily protein-derived peptides with the ability to induce glioma reactive cytotoxic T lymphocytes in human leukocyte antigen-A24+ glioma patients. AB - One promising modality in the treatment of malignant glioma is specific immunotherapy. However, this modality requires information about target antigens and their epitope peptides that are recognized by T cells. In this study, we searched for new target candidates in specific immunotherapy for malignant glioma by utilizing cDNA microarray technology to compare gene expressions in malignant glioma tissues to those in benign glioma and a panel of normal tissues. The selected genes included three members of the kinesin superfamily proteins (KIFs): KIF1C, KIF3C, and KIF21B. RT-PCR showed that these three genes were expressed in the majority of glioma cell lines. These antigen-derived 25 peptides, which had the ability to bind to human leukocyte antigen (HLA)-A24 molecules, were first screened for their ability to be recognized by the immunoglobulin G of glioma patients, and then tested for their potential to induce peptide-specific and glioma-reactive cytotoxic T lymphocytes (CTLs) from the peripheral blood mononuclear cells of HLA-A24+ glioma patients. The results showed that the KIF1C149-158 and KIF3C512-520 peptides efficiently induced HLA-A24-restricted and glioma-reactive CD8+ T cells. These results suggest the existence of KIF-reactive CTL precursors in glioma patients, and should facilitate the development of specific immunotherapies for malignant glioma. PMID- 17273745 TI - Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5 fluorouracil plus oxaliplatin or irinotecan. AB - The aim of this study was to investigate the influence of combining thymidylate synthase (TS), X-ray cross complementing factor 1 (XRCC1) and uridine diphosphate glucoronosyltransferase (UGT1A1 *28) polymorphism genotypes in response rate and time to progression (TTP) in metastatic colorectal cancer patients treated with 5 fluorouracil (5-FU) plus irinotecan or oxaliplatin (OXA). PCR, RFLP, allelic discrimination and direct sequencing were performed to elucidate TS, XRCC1 and UGT1A1 *28 genotypes in blood from 71 patients. Patients with a number of favourable genotypes (NFG) > or =1 had a lower progression rate and a better TTP than patients with NFG=0 (log-rank p<0.03). In the OXA + 5-FU group, patients with the TS 5' single nucleotide polymorphism and/or XRCC1 genotypes favourable to treatment had a better TTP (log-rank p=0.02). The TS 5' tandem repeat polymorphism and the NFG were independent prognostic factors in the Cox-based multivariate analysis (p<0.03). These results confirm the influence on patient out-come of these genetic polymorphisms and the possibility of studying them together to predict the outcome in first-line treated colorectal cancer patients. PMID- 17273746 TI - Regulation of the HIF-1alpha stability by histone deacetylases. AB - Histone deacetylase inhibitors (HDACIs) are currently in clinical trials partly due to their potent anti-angiogenic effects. However, the detailed mechanism of their action is unclear. Here, we observed that several HDACIs (TSA, SB, Apicidin, and VPA) dramatically decreased HIF-1alpha protein level and transcriptional activity of HIF-1 in human and mouse tumor cell lines. Furthermore, class I HDACs, HDAC1 and 3 enhanced HIF-1alpha stability and HIF-1 transactivation function in hypoxic conditions. In addition, immunoprecipitation and in vitro binding assays revealed that HDAC1 and 3 directly bind to the oxygen dependent degradation domain of HIF-1alpha. Collectively, these results suggest that HDAC1 and 3 are considered as a positive regulator of HIF-1alpha stability via direct interaction and may play an important role in HIF-1-induced tumor angiogenesis. PMID- 17273747 TI - Hyperthermia-enhanced tumor accumulation and antitumor efficacy of a doxorubicin conjugate with a novel macromolecular carrier system in mice with non-small cell lung cancer. AB - A novel drug delivery system (DDS) compound was formed by binding doxorubicin hydrochloride (DXR) to the macromolecular carrier carboxymethyldextran polyalcohol (CM-Dex-PA) via the peptidyl spacer (GGFG: Gly-Gly-Phe-Gly). Its use in a murine tumor model confirmed that the DDS (CM-Dex-PA-GGFG-DXR) was retained in the blood and distributed in tumor tissue. The combined use of hyperthermia (HT: 41-42 degrees C for 40 min) and DXR-conjugate (5, 10 or 20 mg/kg i.v.) on tumor accumulation and efficacy was investigated in a murine model of non-small cell lung cancer. Tumor size was measured and the tumor inhibition rate (IR) was calculated. The mean tumor concentration of conjugated DXR in the DXR-conjugate group was 9.40 microg/g compared with 19.04 microg/g in the DXR-conjugate + HT group (p=0.0008). The antitumor efficacy of the DXR-conjugate was significantly enhanced in the groups receiving the combination therapy (p=0.0039, p=0.0250). Significant differences were found between the groups given DXR and those given DXR-conjugate (p=0.0492, p=0.0104). The results demonstrate that the antitumor efficacy of DXR-conjugate is significantly superior to that of DXR alone and the combined use of DXR-conjugate and HT increases the drug's concentration in the tumor, with significant enhancement of antitumor efficacy. PMID- 17273748 TI - Microsatellite DNA instability in nasal cytology of COPD patients. AB - Genetic alterations in the microsatellite DNA level have been successfully detected in sputum samples of patients with COPD and have been shown to be disease specific. Furthermore, previous studies have shown that inflammation coexists in the nasal mucosa of patients with COPD. The aim of this study was to assess the presence of MSI in nasal cytological samples of patients with COPD comparing the results with sputum samples of the same individuals. Nasal brush samples, sputum samples obtained by induction, and peripheral blood from 20 patients with COPD were analyzed. DNA was extracted and analyzed for MSI using the following microsatellite markers: RH70958, D5S207, D6S344, D6S263, G29802, D13S71, D14S588, D14S292 and D17S250. Microsatellite analysis was also performed in 8 healthy non-smokers. MSI was detected in the sputum samples of 7 patients with COPD (35%). In contrast, no microsatellite DNA instability was noted in the nasal cytological samples of the same COPD patients. In addition, no genetic alteration was detected in the control group. These results suggest that MSI is a specific finding for the target organ of COPD, i.e. the lungs, despite the fact that inflammation coexists in the nasal mucosa of COPD patients. Our study supports the hypothesis that MSI could be an index of the somatic-acquired genetic alterations in the lungs of COPD patients. PMID- 17273749 TI - Prospective study of the quantitative carcinoembryonic antigen and cytokeratin 20 mRNA detection in peritoneal washes to predict peritoneal recurrence in gastric carcinoma patients. AB - The prediction of peritoneal recurrence in gastric cancer patients is extremely important in preventing an unfavorable prognosis. In this prospective study, we examined the usefulness of the carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) mRNA detection in peritoneal washes as a prophylactic tool for peritoneal recurrence. Peritoneal washes were obtained from 164 patients with gastric carcinoma during a laparotomy. CEA, CK20 and glyceraldehyde-3-phosphate dehydrogenase mRNA levels in the peritoneal washes were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler. Molecular detection of the CEA and CK20 mRNA in the peritoneal washes by real time RT-PCR showed a significant correlation with tumor size, histological type, depth of invasion, lymphatic invasion, venous invasion, lymph node metastasis, peritoneal dissemination, stage and cytology. The peritoneal recurrence-free survival and overall survival rates of CEA and CK20 mRNA-positive patients were significantly worse than those of marker gene-negative patients. The CEA and CK20 mRNA levels in the peritoneal washes were a significant independent prognostic factor. In conclusion, our prospective study demonstrates that the detection of CEA and CK20 mRNA by quantitative real-time RT-PCR is a useful tool for identifying patients at high risk of peritoneal recurrence who may need adjuvant chemotherapy. PMID- 17273750 TI - Cimetidine induces apoptosis of human salivary gland tumor cells. AB - It has been reported that cimetidine, a histamine type-2 receptor (H2R) antagonist, inhibits the growth of glandular tumors such as colorectal cancer. However, its effects against salivary gland tumors are still unknown. We demonstrated previously that human salivary gland tumor (HSG) cells spontaneously express the neural cell adhesion molecule (NCAM) and also that HSG cell proliferation could be controlled via a homophilic (NCAM-NCAM) binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors. In the present study, we investigated the effects of cimetidine via the expression of NCAM on tumor growth and perineural/neural invasion in salivary gland tumor cells. Expression of both NCAM mRNA and protein was found to decrease in a dose-dependent manner upon treatment with cimetidine for 24 h. The MTT assay and confocal laser microscopy clearly showed that HSG cells underwent apoptosis after treatment with cimetidine. Activation of caspases 3, 7, 8 and 9 was observed in HSG cells after cimetidine treatment, thus confirming that the apoptosis was induced by the activated caspases. Apaf-1 activity was also detected in HSG cells in a dose-dependent manner after treatment with cimetidine. We also found that the cimetidine-mediated down-regulation of NCAM expression in HSG cells did not occur via blocking of the histamine receptor, even though H2R expression was observed on HSG cells, as two other H2R antagonists, famotidine and ranitidine, did not show similar effects. We demonstrated for the first time that cimetidine can induce significant apoptosis of salivary gland tumor cells, which express NCAM, at least in part by down-regulation of NCAM expression on the cells. These findings suggest that the growth, development and perineural/neural invasion of salivary gland tumor cells can be blocked by cimetidine administration through down-regulation of NCAM expression, as well as induction of apoptosis. PMID- 17273752 TI - Assessing serum cytokine profiles in breast cancer patients receiving a HER2/neu vaccine using Luminex technology. AB - We used the Luminex assay to compare serum cytokine profiles of breast cancer patients (BCa) to healthy controls, node-positive (NP) patients to node-negative (NN), and pre- and post-vaccination serum of BCa vaccinated with a HER2/neu E75 peptide vaccine. Sera from 36 pre- and post-vaccination BCa, (12 NP and 24 NN) and 13 healthy, female donors, were evaluated using Luminex technology. Levels of 22 cytokines consisting of interleukin (IL)-1alpha, -1beta, -2, -4, -5, -6, -7, 8, -10, -12, -13, -15, -17, IFN-gamma, G-CSF, GM-CSF, TNF-alpha, IP-10, MIP 1alpha, RANTES, eotaxin and monocyte chemotactic protein-1 (MCP-1) were assessed. Six of 22 cytokines showed significant differences between BCa and healthy controls. MCP-1, eotaxin, RANTES and GM-CSF levels were significantly elevated in BCa (P<0.009) and IL-1alpha and IL-4 levels were significantly decreased in BCa (P<0.015). Cytokine levels were generally elevated in NN patients compared to NP patients with the exception of eotaxin and IL-13, which were increased in NP patients. Three cytokines, IL-6, MIP-1alpha and G-CSF reached statistical significance (P<0.05). In 34 vaccinated BCa, MCP-1, eotaxin and IL-13 were significantly elevated post-vaccination with MCP-1 demonstrating the most significant response (median, 145.8-217.0 pg/ml, P=0.003). Using a multiplex assay we found significant differences in cytokine levels in sera of BCa compared to healthy controls, in NN compared to NP patients, and in vaccinated patients. Our results support an extended analysis of serum cytokine profiles for the potential development of predictive panels in diagnosis, staging and monitoring cancer vaccine trials. PMID- 17273751 TI - Induction of multiple CD8+ T cell responses against the inducible Hsp70 employing an Hsp70 oligoepitope peptide. AB - The inducible heat shock protein Hsp70 has been described as a tumour antigen being frequently overexpressed in tumours of various histologic origins, with a role in tumourigenicity, as a critical event in tumour progression. A strategy to enhance the immune response to an antigen is the identification of multiple epitopes and the induction of a polyspecific response. Applied to tumour vaccination, such a polyspecific response should lead to a more robust antitumour efficacy. The long peptide Hsp70380-402 encompasses three nonamer peptides with a high affinity for HLA-A *0201. In a previous paper, we have shown that two of these nonamer peptides, p391 and p393, can raise CTL to recognize tumour cells overexpressing Hsp70. In the present paper, we demonstrate that the third nonamer peptide, p380, is a new epitope efficient in raising an antitumour immune response. The p380-402 polypeptide was able to induce an immune response against each of the three constituent epitopes both in vivo in HLA-A *0201 transgenic mice and in vitro with human PBMC. This polypeptide therefore constitutes an interesting candidate for the induction of multiple HLA-A *0201-restricted anti Hsp70 antitumour CTL responses. PMID- 17273753 TI - Low postabsorptive net protein degradation in male cancer patients: lack of sensitivity to regulatory amino acids? AB - Autophagic (lysosomal) and proteasomic protein degradation are important regulatory mechanisms in the homeostasis of muscle mass, that may be profoundly disturbed in cancer and other wasting syndromes. Due to the inhibiting effect of amino acids and insulin, net proteolysis is restricted to the fasted state, and in autophagy certain amino acids have been identified as 'regulatory' in the rat, including leucine, tyrosine, phenylalanine, methionine, and histidine (i.e. LYFMH). The present cross-sectional study assessed postabsorptive net protein catabolism in male cancer patients as well as in healthy male volunteers, to analyse its relation to such 'regulatory amino acids'. Postabsorptive amino acid exchange rates across the leg were determined in patients with gastrointestinal cancer (GIC, n=47) or renal cell carcinoma (RCC, n=15), age-matched (n=33), and young male control subjects (n=42). Both groups of cancer patients revealed a significantly lower postabsorptive net protein catabolism than control subjects. Furthermore, in the control subjects, the postabsorptive net protein catabolism was found to be inversely and significantly correlated with the arterial concentrations of the 8 amino acids YSHMFGI and L which include 5 of the 'regulatory amino acids'. Cancer patients, in contrast, revealed no such significant correlations. These results may indicate i) that postabsorptive net protein catabolism in skeletal muscle of healthy subjects may be sensitive to amino acids which reportedly regulate autophagy and ii) that such amino acid sensitive mechanism of protein catabolism may be disturbed in cancer patients. PMID- 17273754 TI - Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT. AB - Photodynamic therapy (PDT) is a promising treatment that is approved by the US FDA for the treatment of oesophageal and lung cancer as well as for age-related macular degeneration. In this study, using standard tissue culture techniques, the photo cytotoxicity and apoptotic mechanisms of Calphostin C (Cal C), a perylenequinone microbial compound in combination with visible light dose was examined in different tumor cell lines. Our results demonstrated both a time and drug-light dose dependence in Cal-C-PDT induced photo toxicity and apoptotic cell death. The induction of apoptosis by Cal C-PDT was found to transit to necrotic cell death at higher drug and light doses. The detection of apoptosis in irradiated tumor cells was performed using various approaches including cell morphology analysis, flow cytometry [DNA fragmentation and phosphatidylserine (PS) externalization] and biochemical assays (activation of caspases). Time course analysis of Cal C cellular uptake and distribution showed a rapid increase within the cellular compartments. The activation of caspases and nuclear fragmentation was evidenced at a maximum time point of 3 h after irradiation. By the use of specific caspase substrates, significant activation of caspase-8 and 3 was found. Mitochondrial involvement during Cal C-PDT-induced apoptosis was proven by a rapid reduction of the mitochondrial membrane potential. Furthermore, Cal C-PDT also enhanced FasL expression, which then induced Fas signalling dependent cell death in NPC and colon cancer cell lines tested. Our results contribute to a deeper understanding of the processes involved in apoptotic cell death following photodynamic treatment with Cal C. PMID- 17273755 TI - IL-3 can not replace GM-CSF in inducing human monocytes to differentiate into Langerhans cells. AB - Receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) share a common beta subunit. We recently reported that GM CSF acts in concert with transforming growth factor-beta1 (TGF-beta1) and Notch ligand Delta-1 (Delta-1) to promote the differentiation of human blood monocytes into Langerhans cells. In the present study, we examined whether IL-3, in place of GM-CSF, can induce the development of Langerhans cells from blood monocytes in the presence of TGF-beta1 and Delta-1, because the IL-3 receptor alpha chain was substantially expressed on monocytes. However, the generation of Langerhans cells was not obtained by the combination of IL-3, TGF-beta1 and Delta-1, even though GM-CSF and IL-3 exhibited a similar effect with respect to the differentiation of monocytes into macrophages and dendritic cells. The addition of GM-CSF to the culture supplemented with IL-3, TGF-beta1 and Delta-1 restored the differentiation of monocytes toward Langerhans cells. A microarray analysis revealed that a number of genes including Langerhans cell markers, E-cadherin and Langerin, were specifically expressed in cells from GM-CSF-containing cultures but not in those from IL-3-containing cultures. These data suggest that IL-3 can not replace GM-CSF to induce the differentiation of human monocytes into Langerhans cells in culture. PMID- 17273756 TI - Obesity increases the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in an ovariectomized Zucker rat model. AB - Obesity is associated with increased risk for postmenopausal, but not premenopausal breast cancer. Recently, we reported that intact obese Zucker rats had increased susceptibility to DMBA-induced mammary tumors compared to lean Zucker rats. In the present study, we investigated whether excessive adipose tissue would promote mammary tumor induction in the absence of ovarian estrogen. Lean and obese rats were sham-operated or ovariectomized at 40 days old and were gavaged at 50 days old with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors and sacrificed 135 days post-DMBA treatment. Obese sham-operated (O/S) rats had a shorter latency period (102 days) compared to lean sham-operated (L/S) (134 days) and obese ovariectomized (O/O) rats (123 days). At the end of the experiment, 36% of the O/O rats developed mammary tumors while lean ovariectomized (L/O) rats developed no mammary tumors (P<0.001), and 59% of the O/S rats developed mammary tumors compared to 30% of the L/S rats (P<0.05). In summary, obesity increases the susceptibility of ovariectomized Zucker rats to DMBA-induced mammary tumors, suggesting that adipose tissue-derived estrogen in obese animals may be sufficient to promote DMBA-induced tumors in this model. These results suggest that obesity in postmenopausal women may increase breast cancer risk due to increased breast tissue exposure to adipose tissue-derived estrogen. In conclusion, we have developed an animal model to further investigate the role of obesity in breast cancer development in postmenopausal women. PMID- 17273757 TI - A novel breast cancer cell line initially established from pleural effusion: evolution towards a more aggressive phenotype. AB - Many human breast cancer cell lines have been in culture for several years, serving as model systems for studying aspects of breast cancer biology. Molecular alterations might occur in these cells during cultivation, and it remains unknown to which extent findings in these cell lines can be related to human disease. Hereby, we describe the establishment of a breast cancer cell line, MW1, from malignant pleural effusion. We compare expression patterns of several molecular markers in breast biopsy tissue, in cultivated tumor cells derived from pleural effusion reflecting the metastatic state, and in late passages of a lineage derived from the pleural culture. Our data show that expression of estrogen and progesterone receptors was lost in the cultivated tumor cells derived from pleural effusion as shown by immunohistochemical staining. Cytokeratin expression patterns remained luminal. During cultivation, the growth rate of MW1 cells increased dramatically and the morphology underwent alterations. As shown by Western blotting, E-cadherin expression remained unchanged whereas P-cadherin expression had increased after 4 years of cultivation of the cell line. Integrin beta4 expression was low in early passages of the pleural effusion whereas the cell line exhibited high expression levels of beta4. HGF receptor (c-Met), EGF receptor, VEGF and VEGF receptor-2 (KDR) expression was detectable by semiquantitative RT-PCR and remained unchanged during cultivation. In contrast, VEGF receptor-1 (flt-1) expression showed lower expression after 4 years of cultivation. The cell line migrated towards HGF, but not towards VEGF. This study provides exemplary insight into the molecular metamorphosis tumor cells undergo in vivo or in vitro on their way from the primary tumor via an equivalent of the metastatic state and during the development of a clonal cell line. PMID- 17273758 TI - Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines. AB - Multiple myeloma (MM) is an incurable hematological disorder characterized by dysregulated proliferation of terminally differentiated plasma cells. Aberrant histone acetylation has been observed in the development of numerous malignancies. Histone deacetylase inhibitors such as valproic acid (VPA) are promising drugs for cancer therapy since they have been reported to have antiproliferative effects and to induce differentiation in carcinoma and leukemic cells. Considering the advantage of being already in clinical use for epilepsy treatment, valproic acid might be a promising therapeutic candidate drug in the management of multiple myeloma. In this study, we show that the short fatty acid VPA has a time and dose-dependent cytotoxic effect on the MM cell lines OPM2, RPMI and U266. The influence of VPA on cell cycle and apoptosis have been evaluated by flow cytometry. Our results show that the three cell lines are blocked in G0/G1 phase. The observed sensitivity to VPA can be partially explained by late apoptosis. Since caspase 3 is activated in all tested cell lines after VPA treatment, a caspase-dependent pathway seems to be involved but not activated by the classic apoptotic pathways. We have also studied another mechanism of cell death, the senescence-like phenotype, but did not find any evidence for its implication. Thus, treatment with VPA may imply other alternative cell death mechanisms. PMID- 17273759 TI - In vitro exposure to 0.57-MHz electric currents exerts cytostatic effects in HepG2 human hepatocarcinoma cells. AB - Capacitive-resistive electric transfer (CRET) therapy is a non-invasive technique currently applied to the treatment of skin, muscle and tendon injuries that uses 0.45-0.6 MHz electric currents to transdermically and focally increase the internal temperature of targeted tissues. Because CRET electrothermal treatment has been reported to be more effective than other thermal therapies, it has been proposed that the electric stimulus could induce responses in exposed tissues that are cooperative or synergic with the thermal effects of the treatment. Previous studies by our group, investigating the nature of the alleged electric response, have shown that short, repeated stimuli with 0.57-MHz currents at subthermal levels could provoke partial, cytotoxic effects on human neuroblastoma cells in vitro. The aim of the present study was to investigate the response from another human cell type, the human hepatocarcinoma HepG2 line, during and after the exposure to 0.57-MHz CRET currents at subthermal densities. The electric stimuli provoked a decrease in the proliferation rate of the cultures, possibly due to an electrically-induced blocking of the cell cycle in a fraction of the cellular population. PMID- 17273760 TI - Identification of neovasculature using nestin in colorectal cancer. AB - CD34 is commonly used as an endothelial cell marker of tumor vessels. However, this marker detects not only newly formed, but also pre-existing large blood vessels. Nestin, a class VI intermediate filament protein, has recently received attention as a marker for detecting newly formed endothelial cells. In this study, whether nestin is a novel angiogenesis marker in colorectal cancer was examined. HCT-15, a human colon cancer cell line, was subcutaneously implanted into the dorsum of nude mice. After the tumor grew, the mice were perfused with fluorescent beads (Fluospheres). Then, the tumor tissues were used for immunofluorescence staining using nestin and the CD34 antibody. Immunohistochemistry was performed with nestin and CD34 on 101 human colorectal cancer tissue samples. Proliferating endothelial cells were detected immunohistochemically by a proliferating cell nuclear antigen (PCNA) antibody. Clinicopathological factors and prognosis were compared between two groups: that with a microvessel density (MVD) higher than the median MVD and that with MVD lower than the median MVD, as detected by nestin and CD34 labellings. Nestin was localized in endothelial cells in small blood vessels (median, 9.06 microm), whereas CD34 was localized in large blood vessels (median, 9.67 microm) in nude mice. The diameter of nestin-positive vessels was smaller than that of CD34 positive vessels in human colorectal cancer. The number ratio of PCNA-positive cells to nestin-positive vascular endothelial cells was higher than that of PCNA positive to CD34-positive cells (p=0.002). There were no correlations between nestin-positive blood vessels and clinicopathological factors, but the prognosis was worse in the highly nestin-positive MVD group (p=0.071). Nestin is considered a novel angiogenesis marker of proliferating endothelial cells in colorectal cancer tissue. PMID- 17273761 TI - Anticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell lines. AB - The natural antioxidant gallic acid (GA) was isolated from fruits of a medicinal Indonesian plant, Phaleria macrocarpa (Scheff.) Boerl. The structure was identified on the basis of spectroscopic analysis and comparison with authentic compound. GA demonstrated a significant inhibition of cell proliferation in a series of cancer cell lines and induced apoptosis in esophageal cancer cells (TE 2) but not in non-cancerous cells (CHEK-1). Observation of the molecular mechanism of apoptosis showed that GA up-regulated the pro-apoptosis protein, Bax, and induced caspase-cascade activity in cancer cells. On the other hand, GA down-regulated anti-apoptosis proteins such as Bcl-2 and Xiap. In addition, GA also induced down-regulation of the survival Akt/mTOR pathway. In non-cancerous cells, we observed delayed expression of pro-apoptosis related proteins. Our results suggest that GA might be a potential anticancer compound. However, in depth in vivo studies are needed to elucidate the exact mechanism. PMID- 17273762 TI - In vitro photodynamic therapy of childhood rhabdomyosarcoma. AB - Treatment of childhood rhabdomyosarcoma is limited by recurrent disease and the development of multidrug resistance. Therefore, novel treatment options are desirable. Photodynamic therapy (PDT) using the photodynamic agent hypericin is proposed as an alternative approach for intraoperative visualization and treatment of this disease. The aim of this study was to investigate in vitro effects of hypericin on childhood rhabdomyosarcoma and to evaluate photodynamic therapy as a possible basis for treatment. Rhabdomyosarcoma cells and fibroblasts (control) were incubated with increasing concentrations of hypericin. in vitro uptake and visualization of hypericin was evaluated by fluorescence microscopy and FACS. For photodynamic therapy, cells were exposed to white light for different time periods. Cytopathologic effects were assessed using standard histology. Cancer cells were investigated for cell viability (MTT assay), proliferative activity (Ki-67 assay), and apoptosis (TUNEL test). A 100% uptake of hypericin was found within the population of rhabdomyosarcoma cells. Uptake of hypericin in the fibroblasts was much less than in rhabdomyosarcoma cells. Hypericin without exposure to white light had no effect on tumor cell viability. After irradiation, PDT resulted in a nearly complete inhibition of cell proliferation of rhabdomyosarcoma cells with a corresponding increase in the frequency of apoptosis. In fibroblasts, PDT was less effective compared to tumor cells. Our data suggest hypericin as a novel tool for visualization and photodynamic therapy of childhood rhabdomyosarcoma. PMID- 17273763 TI - Fibronectin suppression in head and neck cancers, inflammatory tissues and the molecular mechanisms potentially involved. AB - Epithelial cellular fibronectin is frequently repressed after malignant transformation in a variety of cancers. This change has been associated with a loss of contact inhibition. To determine if these findings are unique to malignant processes and to identify mechanisms responsible for fibronectin suppression, we investigated fibronectin expression patterns in 46 head and neck carcinomas, 16 samples of adenoid tissue, and 10 benign mucosal biopsies. We report fibronectin suppression in 78% of the head and neck cancer samples, occurring most prominently within tumor cells, as opposed to the adjacent stroma which exhibited abundant fibronectin. Interestingly, fibronectin was also strongly repressed in chronically inflamed adenoid samples. We showed that fibronectin suppression is mediated by different mechanisms in both benign as well as malignant scenarios: In adenoids, macrophages and T-cells were visualized throughout epithelium that has lost its tight cellular array, allowing leukocyte passage. We have shown that tumor necrosis factor-alpha secreted by macrophages is capable of inducing epithelial derangement via activator protein-1 and nuclear factor-kappaB mediated fibronectin suppression. In head and neck carcinomas, we identified human papilloma virus early protein-2 as a fibronectin transcription inhibitor. We conclude that epithelial fibronectin suppression may not be a hallmark of malignancy, because it can concur with benign processes that involve leukocyte migration. Furthermore, our data suggest that the pattern of fibronectin suppression within the tumor structure largely depends on the cancer cell-stroma relation, which could explain previous conflicting reports on its repression or overexpression along with malignant transformation. In addition, our data support an involvement of human papilloma virus as a mechanism of carcinogenesis mediated via a loss of fibronectin gene expression. PMID- 17273764 TI - CCL21 induces extensive intratumoral immune cell infiltration and specific anti tumor cellular immunity. AB - Chemokines are vital messengers that regulate immune cell activity. The chemokine CCL21 is normally expressed in secondary lymphoid organs and acts as a chemoattractant for several populations of immune cells. Herein, we report that intratumoral CCL21 administration recruited significant numbers of immune cells into murine pancreatic tumors and inhibited tumor growth. Detailed flow cytometric and confocal analysis of CCL21-treated tumor cell isolates revealed increased lymphoid-related dendritic cells (lDC) and myeloid DC (mDC), naive and mature T cells, natural killer (NK) cells, and NKT cells infiltrating the tumor mass. Furthermore, CCL21 intratumoral treatments resulted in significant tumor growth inhibition in wild-type (WT) C57BL/6 mice, but no therapeutic benefit was observed in C57BL/6 RAG2-/-Pfp-/- mice, suggesting that the growth inhibition observed was immunologically mediated. CCL21 intratumoral injections generated immune responses that were tumor-specific and that could be transferred to naive animals via splenocytes. In addition, intratumoral injection of CCL21 into pancreatic tumors reduced the growth of distant tumors as well as treated tumors. Thus, these data demonstrate in a pancreatic tumor model that intratumoral administration of CCL21 can cause significant immune cell infiltration of the tumor mass, delay growth of treated tumors, and generate a tumor-specific cellular immune response. PMID- 17273765 TI - The low-toxicity 9-cis UAB30 novel retinoid down-regulates the DNA methyltransferases and has anti-telomerase activity in human breast cancer cells. AB - Retinoic acids and their derivatives potentiate anti-cancer effects in breast cancer cells. The aberrant expression of telomerase is critical to the continued proliferation of most cancer cells. Thus, telomerase is an attractive target for chemoprevention and treatment of breast cancer. 9cUAB30 is a novel synthetic retinoid X receptor-selective retinoic acid (RA) that effectively reduces the tumorigenic phenotype in mouse breast carcinoma with lower toxic effects than natural retinoid treatments. We have assessed 9cUAB30 retinoic acid treatment of human breast cancer cells to determine the potential of this drug as an effective telomerase inhibitor and its application to cancer therapy. 9cUAB30 was found to decrease DNA methyltransferase and telomerase expression in MDA-MB-361, T-47D, and MCF-7 human breast cancer cells and to inhibit the proliferation of these cells. This low-toxicity retinoid also reduced colony formation in soft agar assays in each of these cell types. Combination treatments of 9cUAB30 and all trans RA proved to be synergistically more effective than either RA alone, further suggesting a possible general epigenetic mechanism that contributes to the anti-telomerase activity of the retinoids. Therefore, the novel retinoid, 9cUAB30, is effective in inhibiting the growth of human breast cancer cells, its anti-cancer effects appear to be related to telomerase inhibition and the mechanism for this process could be mediated through epigenetic modifications. PMID- 17273766 TI - Predicting survival of children with CNS tumors using proton magnetic resonance spectroscopic imaging biomarkers. AB - Using brain proton magnetic resonance spectroscopic imaging (MRSI) in children with central nervous system (CNS) tumors, we tested the hypothesis that combining information from biologically important metabolites, at diagnosis and prior to treatment, would improve prediction of survival. We evaluated brain proton MRSI exams in 76 children (median age at diagnosis: 74 months) with brain tumors. Important biomarkers, choline-containing compounds (Cho), N-acetylaspartate (NAA), total creatine (tCr), lipids and/or lactate (L), were measured at the "highest Cho region" and normalized to the tCr of surrounding healthy tissue. Neuropathological grading was performed using World Health Organization (WHO) criteria. Fifty-eight of 76 (76%) patients were alive at the end of the study period. The mean survival time for all subjects was 52 months. Univariate analysis demonstrated that Cho, L, Cho/NAA and tumor grade differed significantly between survivors and non-survivors (P< or =0.05). Multiple logistic regression and stepwise multivariate Cox regression indicated that Cho + 0.1L was the only independent predictor of survival (likelihood ratio test = 10.27, P<0.001; Cox regression, P=0.004). The combined index Cho + 0.1L was more accurate and more specific predictor than Cho or Cho/NAA. Accuracy and specificity for Cho + 0.1L were 80% and 86%, respectively. We conclude that brain proton MRSI biomarkers predict survival of children with CNS tumors better than does standard histopathology. More accurate prediction using this non-invasive technique represents an important advance and may suggest more appropriate therapy, especially when diagnostic biopsy is not feasible. PMID- 17273767 TI - Photodynamic therapy of malignant glioma with hypericin: comprehensive in vitro study in human glioblastoma cell lines. AB - The poor prognosis of patients suffering from malignant glioma requires further efforts. Photodynamic therapy (PDT) might be a therapeutic option to increase surgical radicality. Hypericin (HY) exhibit high phototoxicity to malignant cells and accumulates to a higher extent in glioblastoma cells as compared to neurons. Therefore, the impact of various experimental parameters on cytotoxicity, intracellular accumulation and phototoxicity of HY was quantitatively assessed in the three human glioblastoma cell lines U373 MG, LN229 and T98G. Additionally, intracellular location of HY was studied with fluorescence microscopic techniques. For all three cell lines, no cytotoxicity was found for incubation concentrations up to 5 microM. For short-time incubation (2 h), maximum HY fluorescence was achieved at an incubation concentration of about 5 microM. However, uptake kinetics of HY was dependent on its incubation concentration. Moreover, increase in HY fluorescence was negligible at 4 degrees C, which strongly indicates that the compound is taken up by an energy-dependent process. HY exhibited high phototoxicity (at 595 nm) in all three cell lines with ID50 values ranging from 0.15 J/cm(2) to 0.22 J/cm(2), but sensitivity decreased in the order U373 MG > LN229 > T98G. However, assessment of phototoxicity at different wavelengths revealed that highest cell inactivation was achieved at 600 nm. Fluorescence microscopy showed that HY fluorescence arose predominantly from the perinuclear region and the nuclear membrane. Fluorescence pattern of HY was significantly different from those observed for organelle markers staining lysosomes or mitochondria. Location of HY in the plasma membrane was proven by total internal reflection fluorescence microscopy. Thus, the present study demonstrates that glioblastoma cells can be effectively inactivated by HY-PDT after short-time incubation and exposure to low light doses. These results obtained in cell culture are encouraging and justify further evaluation HY-PDT for the treatment of malignant glioma in animal experiments. PMID- 17273768 TI - Sense p16 and antisense uPAR bicistronic construct inhibits angiogenesis and induces glioma cell death. AB - High-grade gliomas comprise the most malignant type of primary brain tumor and are relatively frequent in adults. Recent studies have indicated that the loss of p16, an inhibitor of CDK4, promotes the acquisition of malignant characteristics in gliomas. A correlation between overexpression of urokinase-type plasminogen activator receptor (uPAR) and glioblastoma invasion has also been established. Moreover, uPAR/integrin binding has been shown to initiate or potentiate integrin signaling through focal adhesion kinase and/or src kinases. Our previous studies demonstrated that downregulation of uPAR expression and restoration of p16 regress glioma growth in nude mice and downregulate alphavbeta3 integrin receptor expression. Here, we show the effect of a bicistronic construct on alphavbeta5 integrin receptor expression, angiogenesis and the biochemical pathway that causes glioma cell death. The U251 glioblastoma and a glioblastoma xenograft cell line transduced with a recombinant replication-defective adenovirus vector containing the cDNA of wild-type p16 and antisense RNA of uPAR significantly inhibited human mammary epithelial cell capillary formation and vascular endothelial growth factor (VEGF) expression. Inactivation of anti-apoptotic molecules such as Akt, PARP, activation of caspases and accumulation of heteroduplex chromosomal DNA in pre-G1 phase of the cell cycle was demonstrated by Western blotting, caspase activity assay and FACS analysis. Nuclear DNA fragmentation upon induction of apoptosis was scored using the TUNEL assay. Significant downregulation of alphavbeta5 integrin receptor expression was also confirmed by FACS analysis, immunoprecipitation and RT-PCR. Taken together, the results demonstrate that the sense p16 and anti-sense uPAR bicistronic construct significantly inhibits angiogenesis, induces apoptosis by deregulation of the PI3K-Akt pathway and downregulates alphavbeta5 integrin receptor expression. PMID- 17273770 TI - Methylation status of the SOCS3 gene in human malignant melanomas. AB - The suppressors of cytokine signaling (SOCS) family inhibits not only Janus kinase (JAK)/signal transducers and activators of transcription (STAT) but also focal adhesion kinase (FAK) signaling pathways, and has tumor suppressor activity. Aberrant methylation in the promoter region of the SOCS3 gene frequently occurs in several types of human malignancy, and its transcriptional silencing is associated with malignant tumor behavior. In malignant melanomas, the expression and methylation status of the SOCS3 gene have not been elucidated. We therefore examined the methylation status and/or protein expression of the SOCS3 gene in 5 human malignant melanoma cell lines, 2 primary cultures of normal melanocytes, and surgically resected tumors (5 malignant melanomas and 2 melanocytic nevi). Four of the 5 melanoma cell lines and the 2 primary cultures of normal melanocytes expressed SOCS3 protein to various degrees, and only one melanoma cell line was negative. Expression of SOCS3 protein was inversely correlated with methylation status in the SOCS3 promoter region, and treatment with a demethylating agent (5-aza-2'-deoxycytidine) was able to induce expression of the protein in one melanoma cell line that was SOCS3-negative and another that was weakly positive. Three of the 5 primary malignant melanomas and one of the 2 melanocytic nevi showed aberrant methylation. These results suggest that inactivation of the SOCS3 gene by hypermethylation may be involved in the promotion of malignant behavior of melanomas. PMID- 17273769 TI - Fenretinide up-regulates DR5/TRAIL-R2 expression via the induction of the transcription factor CHOP and combined treatment with fenretinide and TRAIL induces synergistic apoptosis in colon cancer cell lines. AB - Fenretinide (N-[4-Hydroxyphenyl]retinamide; 4HPR) is a semisynthetic retinoid that induces apoptosis in a variety of malignancies. Fenretinide has been examined in clinical trials as a cancer chemopreventive and chemotherapeutic agent. Oxidative stress induced by fenretinide has been shown to mediate apoptosis through a mitochondrial pathway by the induction of a transcription factor CCAAT/enhancer binding protein homologous protein (CHOP) and Bak. In this study, we report that fenretinide induces death receptor 5 (DR5)/TRAIL-R2 up regulation via the induction of the transcription factor CHOP in colon cancer cell lines. Fenretinide induced DR5 expression at protein and mRNA levels. Furthermore, fenretinide increased DR5 promoter activity and the enhanced activity decreased by mutation of the CHOP binding site. CHOP was also up regulated by fenretinide at the promoter level. We also showed that combined treatment with fenretinide and TRAIL induced synergistic apoptosis in colon cancer cell lines. The synergistic apoptosis was markedly blocked by DR5/Fc chimeric protein. Fenretinide and TRAIL cooperatively activated caspase-3, -8, 10 and -9 and cleavage of Bid and PARP, and this activation was also blocked in the presence of DR5/Fc chimeric protein. These results indicate that fenretinide induced apoptosis is sensitized by TRAIL. Therefore, combined treatment with fenretinide and TRAIL might be a promising model for the treatment of colorectal cancer. PMID- 17273771 TI - Synergistic effect of survivin-specific small interfering RNA and topotecan in renal cancer cells: topotecan enhances liposome-mediated transfection by increasing cellular uptake. AB - Survivin, an inhibitor of apoptosis (IAP) protein detected in many tumors but not in most normal differentiated tissues, has been widely recognized as an attractive target for cancer therapy. We previously showed that survivin expression is associated with cell proliferation. Although liposome-mediated transfection of survivin-specific siRNA decreases survivin expression and cell proliferation, these effects are limited in part by the low efficiency of the transfection. In the present study we therefore investigated the possibility of better suppressing survivin expression and cell growth by using treatments combining survivin-specific siRNA and the topoisomerase I inhibitor topotecan. Survivin-specific siRNA and topotecan given simultaneously inhibited survivin expression and cell proliferation synergistically, but topotecan alone or topotecan and siRNA given metachronously did not alter survivin expression. We hypothesized that topotecan increases the efficiency of siRNA transfection by increasing cellular uptake, and we confirmed this hypothesis by using fluorescein labeled siRNA. Combination therapy using survivin-specific siRNA and topotecan should thus show a synergistic effect due to increased cellular uptake of siRNA and offer an attractive approach for treatment of advanced renal cancer. PMID- 17273772 TI - Glioma cells suppress hypoxia-induced endothelial cell apoptosis and promote the angiogenic process. AB - The hypoxic microenvironment of solid tumors is associated with malignant progression and it renders tumors more resistant to cancer therapies. Endothelial cell damage may occur following hypoxic conditions and lead to dysfunction; however, endothelial cells in tumors survive hypoxic conditions providing nutrients and oxygen to facilitate tumor growth. In this study, we investigated the effects of tumor-conditioned medium on hypoxia-induced changes in endothelial cell growth, migration and survival. Tumor conditioned medium collected from U87 human glioblastoma cells were applied to endothelial cultures in normoxia or hypoxia conditions. Hypoxia caused a reduction in clonogenic cell survival response and an increase of the sub-G1 phase of the cell cycle in endothelial cells. Cell migration was measured by spheroid and wound-induced migration assays and hypoxia compared with normoxia significantly increased the number of migrating endothelial cells. Nuclear staining with Hoechst 33258 and caspase-9 and -3 activation in endothelial cells show that hypoxia-induced apoptosis involves caspase-dependent mechanism. Exposure to hypoxia caused an increase in gene expression of VEGF and VEGFR2 and activities of MMP-2 and MMP-9. Furthermore, hypoxia induced an increase in capillary-like structure formation in endothelial cells seeded into Matrigel. Tumor conditioned medium enhanced survival and rescued endothelial cells from apoptosis induced by hypoxia. These molecular changes in endothelial cells could, in part, contribute to the angiogenic response that occurs during hypoxia-induced angiogenesis in glial tumors. PMID- 17273773 TI - Diverse activation states of RhoA in human lung cancer cells: contribution of G protein coupled receptors. AB - Rho GTPases play an essential role in the control of various cellular functions. Accumulating evidence suggests that RhoA overexpression contributes to human cancer development. However, the activation states of RhoA are poorly defined in cancer cells. In this study, we examined both the expression levels and the activation states of RhoA in various lung cancer cells by quantitative real-time reverse transcriptase-polymerase chain reaction and in vivo Rho guanine nucleotide exchange assay, respectively. Moreover, we dissected the signaling pathway from the cell surface receptors to RhoA using a broad-spectrum G protein coupled receptor (GPCR) antagonist, [D-Arg1,D-Trp5,7,9,Leu11]Substance P (SP), and a recently reported Galphaq/11-selective inhibitor, YM-254890. We found that RhoA was expressed highly in large cell carcinoma cells but only weakly in adenocarcinoma cells. The activation states of RhoA are considerably different from its expression profiles. We found that four of six small cell lung carcinoma (SCLC) cell lines exhibited a moderate to high activation rate of RhoA. The addition of [D-Arg1,D-Trp5,7,9,Leu11]SP reduced RhoA activity by almost 60% in H69 SCLC cells. The addition of YM-254890 had no effect on RhoA activity in H69 cells. Our results suggest that RhoA is activated in various lung cancer cells independent of its expression levels, and the high activation state of RhoA in SCLC cells mainly depends on a neuroendocrine peptide autocrine system which signals through Galpha12 coupled GPCR to RhoA. This study provides new insights into RhoA signaling in lung cancer cells and may help in developing novel therapeutic strategies against lung cancer. PMID- 17273775 TI - Prognostic factors for surgical outcome and survival in 447 women treated for advanced (FIGO-stages III-IV) epithelial ovarian carcinoma. AB - The objectives of this population-based, retrospective study, was to find predictive factors for surgical outcome and long-term survival in 447 patients with epithelial ovarian cancer in FIGO-stages III-IV treated during 1975-1993. The median overall survival rate of this series was 18 months, the 5-year cancer specific survival rate was 18%, and the 5-year overall survival rate, 16%. In a logistic regression analysis, type of surgeon was the strongest (P=0.006) predictive factor for surgical outcome after the age of the patient. The optimal debulking rate was 36% for gynecologic oncologists, 29% for general gynecologists, 24% for combined gynecologist and obstetrician with the third level of specialization, and 4% for general surgeons. Optimal debulking (no visible tumor or residual tumor <2 cm) was achieved in 26% of the cases. Predictive factors of the outcome of cytoreduction were FIGO-stage (P=0.007), histological subtype (P=0.016), and tumor grade (P=0.046) in univariate analyses. In a Cox multivariate analysis the most important prognostic factor for overall survival was the amount of residual cancer (P=0.000001) before age, grade and stage. Therefore, to achieve optimal surgical outcome and optimal overall survival rate the primary surgery of advanced ovarian cancer should be performed by gynecologic oncologists or by gynecologists specially trained in gynecologic cancer surgery. PMID- 17273774 TI - Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. AB - RALBP1 (RLIP76) is the major transporter of doxorubicin (DOX) in lung cancer cells, and that the difference in sensitivity of small cell lung cancer (SCLC) cells to DOX is due to differential phosphorylation by PKCalpha. Our recent studies have suggested that RALBP1 present in MCF-7 breast cancer cells has significantly lower specific activity for transport of DOX than wild-type recombinant protein, and its level of expression is significantly lower than that in lung cancer cells. In the present study, we have explored whether or not this is a generalized phenomenon for breast cancer, and have compared the relative contributions of RALBP1 and the ABC-family transporter, ABCG2 to total DOX transport activities in two SCLC (H1417 and H1618), two non-small cell lung cancer (NSCLC) (H358 and H520), and three breast cancer (T-47D, MDA-MB231, and MCF-7) cell lines. Results of these studies show lower protein expression and specific activity of RALBP1 in all three breast cancer cell lines as compared with lung cancer cell lines. Furthermore, we demonstrate that RALBP1 contributes only a minor fraction of DOX transport activity in breast cancer cell lines, suggesting that greater DOX sensitivity of breast cancer may be related to lower RALBP1 transporter activity and that the transport mechanisms involved in multidrug resistance of lung and breast cancer are distinct. PMID- 17273776 TI - Geographic variation in follow-up after rectal cancer surgery. AB - Most patients with rectal cancer are treated with curative-intent surgery; adjuvant chemotherapy and radiation are often used as well. A recent survey of members of the American Society of Colon and Rectal Surgeons (ASCRS) revealed considerable variation in surveillance intensity after primary treatment. We evaluated whether geographic factors may be responsible for the observed variation. Vignettes of hypothetical patients and a questionnaire based on the vignettes were mailed to the 1782 members of ASCRS. Repeated-measures analysis of variance was used to compare practice patterns, as revealed by the responses, according to US Census Regions and Divisions, Metropolitan Statistical Areas (MSA), and state-specific managed care organization (MCO) penetration rates. There was significant variation in surveillance intensity according to the US Census Region and Division in which the surgeon practiced. Non-US respondents employed CT of the abdomen and pelvis, chest radiography, and colonoscopy significantly more often than US respondents. MSA was not a significant source of variation. Surveillance patterns varied significantly by MCO penetration rate for office visits and CT of the abdomen and pelvis but not for other modalities. The US Census Region and Division in which the surgeon practices have a significant effect on surveillance intensity following completion of primary curative-intent therapy for rectal cancer patients. The MSA in which the surgeon practices does not affect surveillance intensity significantly and MCO penetration rate affects follow-up intensity minimally. All significant differences are clinically rather modest, however. These data should be useful in the design of controlled trials on this topic. PMID- 17273777 TI - Pre-analytic saliva processing affect proteomic results and biomarker screening of head and neck squamous carcinoma. AB - The objective of this study was to assess the effect of pre-analytical processing on proteomic analysis of saliva and to identify salivary biomarkers for potential clinical applications. Saliva samples from five healthy individuals and three head and neck squamous carcinoma (HNSC) patients were initially depleted of major protein constituents. Saliva from healthy subjects was divided and processed by three different methods prior to liquid chromatography and tandem mass spectrometry technique (LC-MS/MS) analysis. The results showed marked differences amongst the methods. The SDS-PAGE separation and in-gel digestion method yielded the highest number of proteins that included the majority of those identified by the other two methods. The in gel-digestion method was used in the LC-MS/MS analysis of saliva from three HNSC patients and the results were compared with those from healthy subjects. Our analysis identified two proteins, alpha-1-B glycoprotein and complement factor B proteins, to be present in patients but not in normal specimens. Paradoxically, cystatin S, parotid secretory factor, and poly-4-hydrolase beta-subunit proteins were detected in most normal salivas but not in patient specimens. Subsequent analysis of complement factor B by Western blotting showed strong immunoreactive bands of complement factor B in HNSC patients' and negative or weakly positive in normal saliva samples. We conclude that: 1) initial saliva processing affects protein analysis, 2) in-gel digestion followed by LC-MS/MS detects the most saliva proteins, 3) certain proteins are differentially found in patient and normal salivas and 4) a small set of proteins can be targeted for future validation for clinical investigation. PMID- 17273778 TI - Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer. AB - Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate FGF20, JAG1, DKK1, WISP1, CCND1 and MYC genes for cell-fate determination, while non-canonical WNT signals are transduced through FZD family receptor and ROR2/PTK7/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NLK and NFAT signaling cascades for the regulation of tissue polarity, cell movement, and adhesion. We previously reported molecular cloning and characterization of human FZD5, which showed six amino-acid substitutions with human Hfz5. FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology. Here, comparative integromics analyses on FZD5 orthologs were performed by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD5 and cow Fzd5 genes were identified within NW_104292.1 and AC166656.2 genome sequences, respectively. FZD5 orthologs were seven-transmembrane proteins with extracellular Frizzled domain, leucine zipper motif around the 5th transmembrane domain, and cytoplasmic DVL- and PDZ binding motifs. Ser523 and Ser529 around the DVL-binding motif of FZD5 orthologs were putative aPKC phosphorylation sites. POU5F1 (OCT4)-binding site linked to SP1-binding site within the 5'-promoter region of human FZD5 gene was evolutionarily conserved among mammalian FZD5 orthologs. POU5F1 was more related to POU2F and POU3F subfamily members. POU5F1 was preferentially expressed in undifferentiated human embryonic stem (ES) cells, pancreatic islet, and diffuse type gastric cancer. POU2F1 (OCT1) was expressed in ES cells, fetal liver/spleen, adult colon, POU2F2 in ES cells, fetal liver/spleen, and POU2F3 in diffuse-type gastric cancer. Multiple SP1/KLF family members, other than KLF2 or KLF4, were expressed in undifferentiated human ES cells. Together, these facts indicate that POU5F1 and POU2F subfamily members play a pivotal role for the FZD5 expression in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer. PMID- 17273779 TI - Electrostatic modeling of peptides derived from the V3-loop of HIV-1 gp120: implications of the interaction with chemokine receptor CCR5. AB - Infection of CD4+ T cells by macrophage-tropic HIV-1 strains involves interaction of viral gp120 with the host cell chemokine receptor CCR5. The principle neutralizing determinant (PND) of the V3-loop of the HIV-1 gp120 was investigated for its interaction with CCR5 by computational modeling methods at atomic resolution and electrostatic calculations to complement experimental findings. The study focused on the recognition step and examined possible peptide-peptide interactions between various PND-derived peptides from the V3-loop and the N terminal (Nt) domain of CCR5. These recognition interactions are possible because of the complementary character of the spatial distribution of the predominantly positive electrostatic potentials of the PND-derived peptides and the predominantly negative electrostatic potential of the CCR5Nt domain. The CCR5Nt appears more amenable to interaction with the V3 peptides, than the other CCR5 extracellular domains (ECL), because of its length and the domination of its negative electrostatic potential. On the contrary, ECL2 possesses a predominantly positive electrostatic potential. There are positive patches in Nt and negative patches in ECL2, which, following the non-specific recognition of the V3-loop by CCR5 and with the expected local structural rearrangements to facilitate specific binding, may be contributing to the stabilization of the complex. A sequential two-step specific binding, involving different extracellular domains, is conceivable. Although the electrostatic potentials may play a role in a V3-CCR5 interaction, a more specific model cannot be derived in the absence of a three dimensional structure of a gp120/CD4/CCR5 complex. PMID- 17273781 TI - REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer. AB - Human testicular cancer is very sensitive to chemotherapy and radiation therapy and is regarded as a curable cancer. The cancer prevails in the young reproductive generation and testicular dysfunction is often observed as a side effect, remaining a serious challenge. In the present study, we examined the potential utility of REIC/Dkk-3-based gene therapy against human testicular cancer. Expression of REIC/Dkk-3 was reduced in all of the human seminoma and non seminomatous germ cell tumor tissues. Overexpression of REIC/Dkk-3 using an adenovirus vector (Ad-REIC) induced apoptosis in a testicular germ cell cancer cell line NCCIT but not in normal human fibroblasts. c-Jun terminal kinase (JNK) was activated by Ad-REIC and the induction of apoptosis was abrogated by a JNK inhibitor. A single intratumoral injection of Ad-REIC markedly inhibited the tumorigenic growth of NCCIT cells in nude mice. These results indicate that Ad REIC may lead to developing less insulting and non-genotoxic therapeutic measures against human testicular cancer. PMID- 17273780 TI - Iberin induces cell cycle arrest and apoptosis in human neuroblastoma cells. AB - Epidemiological studies have indicated that increased consumption of cruciferous vegetables is associated with a statistically significant reduction in the risk for cancers. The major bioactive agent in these vegetables is a class of sulfur containing glycosides called glucosinolates. Isothiocyanates, derivatives of glucosinolates, have been shown to possess anticancer properties in a variety of tumor cell lines. In this study, we evaluated the antigrowth, cell cycle modulation and proapoptotic effects of isothiocyanate iberin in human neuroblastoma cells. Treatment of neuroblastoma cells with iberin resulted in a dose- and time-dependent inhibition of growth, increased cytotoxicity, and G1 or G2 cell cycle arrest depending upon cell type. The iberin-induced cell cycle arrest in neuroblastoma cells was associated with inhibition of expression of Cdk2, Cdk4, and Cdk6 proteins. Fluorescence microscopic analysis of DNA-staining patterns with DAPI revealed an increase in apoptotic cell death in iberin-treated cells as compared with control cells. FLICA staining showed that iberin induced apoptosis, and this apoptotic induction was found to be associated with the activation of caspase-9, caspase-3, and PARP. These findings suggest that the anticancer efficacy of iberin is mediated via induction of cell cycle arrest and apoptosis in human neuroblastoma cells and has strong potential for development as a therapeutic agent against cancer. PMID- 17273782 TI - A W148R mutation in the human FOXD4 gene segregating with dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality. AB - The forkhead/winged helix box (FOX) gene family comprises at least 43 different genes encoding transcriptional factors with a highly conserved DNA-binding domain. To date, mutations in members of the FOX gene family have been causally linked to a variety of different human diseases. We describe a three-generation Albanian pedigree in which a complex phenotype consisting of dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality is segregated with a missense mutation (W148R) in the human FOXD4 gene. This mutation disrupts an extremely highly conserved tryptophan residue in the forkhead domain of FOXD4, possibly resulting in reduced DNA binding capacity and altered transcriptional activity. Our present findings widen the spectrum of diseases associated with genetic aberrations in the forkhead gene family. PMID- 17273783 TI - Comano's (Trentino) thermal water interferes with tumour necrosis factor-alpha expression and interleukin-8 production and secretion by cultured human psoriatic keratinocytes: yet other mechanisms of its anti-psoriatic action. AB - Thermal balneotherapy with Comano's spa water (CW; Trentino, Italy) is beneficial for psoriasis and other skin disorders but its operative mechanisms are largely unknown. Previously, we showed that CW interferes with the production and secretion of IL-6 and various VEGF-A isoforms and with CK-16 expression by cultured human psoriatic keratinocytes. In this study, confluent cultures of epidermal keratinocytes isolated from the lesional areas of 9 psoriatic patients were exposed for 11-13 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells), in order to assess the expression and secretion of TNF-alpha and IL-8 by such cells. The results gained by means of immunocytochemistry, Western immunoblotting (WB), and ELISA assays showed that CW exposure significantly down-regulated the intracellular levels of TNF-alpha, a key inducer of IL-8, IL-6, and other chemokines. However, no assayable TNF-alpha secretion occurred in keratinocyte conditioned DW- and CW-DMEM samples. Moreover, the intracellular levels and secretion rates of IL-8 were also markedly reduced in the protein extracts and conditioned media of CW-DMEM-incubated keratinocytes. Notably, the most effective inhibition of IL-8 secretion was elicited by a 25% CW fraction in the DMEM. Altogether, our findings indicate that by attenuating at lesional skin sites the deregulated production and secretion of a cascade of several cytokines and chemokines (e.g. TNF- alpha, IL-8, IL-6, and various VEGF-A isoforms), and by offsetting the keratinocytes' abnormal differentiation program entailing CK-16 expression, CW balneotherapy may beneficially influence the clinical manifestations of psoriasis. PMID- 17273784 TI - Involvement of transforming growth factor-beta in the expression of gicerin, a cell adhesion molecule, in the regeneration of hepatocytes. AB - Gicerin, an Ig-superfamily cell adhesion molecule, appears transiently in embryonic tissues including those of the nervous, urogenital, respiratory and digestive systems, and it promotes neurite extension, cell migration and epithelialization through its cell adhesive activities. In addition, gicerin also reappears in regenerating tissue after suffering either a traumatic injury or a viral infection. In the present study, we examined the expression pattern of gicerin in the regeneration of hepatocytes. Immunohistochemically, gicerin protein appeared in the regenerating hepatocytes of carbon tetrachloride (CCl4) induced acute hepatitis, while it was scarcely expressed in the hepatocytes of normal mouse liver. Real-time PCR revealed the up-regulation of gicerin transcription in the regenerating process of CCl4-induced hepatitis. The expression of transforming growth factor (TGF)-beta1 was also increased during the regeneration. Furthermore, the gicerin mRNA expression increased during the process of an in vitro hepatocyte regeneration model using mouse primary hepatocytes and hepa 1-6 cells. To note, the mRNA levels of gicerin in these cells were enhanced by the presence of TGF-beta1. Collectively, these findings suggest that TGF-beta1 may therefore regulate gicerin expression in hepatocytes leading to liver regeneration by cell-cell or cell-ECM interactions. PMID- 17273785 TI - Adipocyte differentiation of human marrow mesenchymal stem cells reduces the supporting capacity for hematopoietic progenitors but not for severe combined immunodeficiency repopulating cells. AB - Bone marrow stromal cells provide a microenvironment for hematopoiesis. Adipocytes are the major stromal cell phenotype in bone marrow, but their function in hematopoiesis is poorly understood. In this study, we compared the hematopoietic-supporting capacity of adipocytes and their progenitor, mesenchymal stem cells (MSCs), by culturing human cord blood (CB) CD34+CD38- hematopoietic progenitor cells (HPCs) on a layer of adipocytes or MSCs. CB CD34+CD38- cells cultured on MSCs generated higher proportions of CD34+CD38- HPCs and colony forming cells than those cultures on a layer of adipocytes, indicating an inferior hematopoietic support by adipocytes. However, CB CD34+CD38- HPCs cultured on MSCs and adipocytes were equally capable of reconstituting human hematopoiesis in non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice. These findings show that differentiation of MSCs into adipocytes is accompanied by the loss of capacity to support mature HPCs, but not transplantable SCID-repopulating cells. PMID- 17273786 TI - Vacuolar-type H+-ATPase-mediated acidosis promotes in vitro osteoclastogenesis via modulation of cell migration. AB - Localized acidification of the osteoclast-bone interface is driven by a vacuolar type H+-ATPase (V-ATPase) in the plasma membrane in a process thought to be associated with bone resorption. The present study investigated the mechanism underlying the roles of V-ATPase-induced acidosis in osteoclastogenesis. Active proton pumping due to increased V-ATPase activity during RANKL-induced osteoclastogenesis induced intracellular and extracellular acidification of osteoclast precursors. Subsequent analysis revealed blockage of extracellular acidification and induction of intracellular acidification by bafilomycin A1, a specific inhibitor of V-ATPase, indicating that extracellular acidification is mostly induced by V-ATPase-mediated proton pumping into extracellular space. Low pH media controlled by HEPES-buffered conditions to mimic metabolic acidosis led to synergistic activation of RANKL-stimulated signals, including mitogen activated protein kinases and transcription factor NF-kappaB, resulting in enhanced osteoclastogenesis. Low-pH media also upregulated the expression of osteopontin secreted into extracellular space, which is required for cell migration by binding to cell surface integrin alphavbeta3. Osteoclast precursor migration was significantly inhibited by treatment of antibodies to integrin alphavbeta3, resulting in the retardation of osteoclastogenesis. Taken together, these findings indicate that V-ATPase-driven acidosis modulates osteoclastogenesis. PMID- 17273787 TI - Neuropeptide W exerts a potent suppressive effect on blood leptin and insulin concentrations in the rat. AB - Neuropeptide B/W receptor 1 (NPBWR1) and neuropeptide B/W receptor 2 (NPBWR2) are two structurally related orphan receptors linked to protein G. In rodents NPBWR2 is absent, and its counterpart is described as being similar to neuropeptide B/W receptor 2. Endogenous ligands of these receptors have been identified. One of them is 29 amino acid residues long, uniquely modified with bromine and, thus, termed neuropeptide B (NPB). The other, neuropeptide W (NPW), has been identified in two molecular forms of 23 and 30 amino acids (NPW23 and NPW30), respectively. Both NPB and NPW affect food intake and energy expenditure. Since leptin, a potent anti-obesity hormone, and insulin are involved in the control of energy homeostasis, the present study aimed to investigate whether NPB and NPW affect leptin and insulin secretion in the rat. RT-PCR technique revealed the presence of ppNPB, ppNPW, NPBWR1 and NPBWR2-like mRNAs in isolated pancreatic islets of the rat. NPB and NPW immunoreactivities were observed in all of the cells of the pancreatic islets. Only when a higher dose was administered (3 nmol/100 g body weight) did NPW transiently lower blood insulin levels whereas NPB injection did not alter insulinaemia in the studied rats. At 30 min, but not 60, of the experiment, NPW notably lowered blood leptin concentrations at both tested doses. On the contrary, NPB injections had no effect on blood leptin and insulin concentrations. Thus, the results suggest that NPW but not NPB exerts a potent suppressive effect on blood leptin concentrations in the rat, and this mechanism may be involved in NPW regulation of energy homeostasis. PMID- 17273788 TI - Expression of aquaporin-1 in endometrial blood vessels in menorrhagia. AB - Aquaporin-1 (AQP1) is a water channel protein expressed in vascular endothelia and involved in impaired angiogenesis in tumors. Since angiogenesis is an essential component of the regeneration of the endometrium, we sought to analyze the expression of AQP1 in endometrial blood vessels in normal cyclic endometrium as well as in endometrial biopsies of menorrhagia patients. Endometrial biopsies from 16 patients with menorrhagia and 21 healthy fertile women were used for immunohistochemistry assessment of AQP1-stained endothelial structures. RT-PCR was used to confirm the presence of AQP1 mRNA. We detected the expression of AQP1 solely in endometrial blood vessels in the control group, as well as in menorrhagic endometrium. There was no difference between proliferative and secretory endometrium. Furthermore, we observed that the vascular expression of AQP1 in endometrial blood vessels in the menorrhagia group was significantly lower than in controls (p=0.002). There was also a significantly lower number of stained vessels per unit area in the menorrhagia group than in the controls (p=0.006). Thus, the deregulation of aquaporin-1 in menorrhagia may be involved in abnormal endometrial vascular growth and permeability. PMID- 17273789 TI - De-repression of heat shock transcription factor-1 in interleukin-6- treated hepatocytes is mediated by downregulation of glycogen synthase kinase 3beta and MAPK/ERK-1. AB - Expression of inducible heat shock protein (HSP70) requires activation of heat shock transcription factor-1 (HSF-1). Recent evidence suggests that interleukin-6 (IL-6) can modify the response of HSF-1 to heat. We hypothesized that IL-6 would prime the HSP response by causing de-repression of HSF-1 resulting in augmented HSP expression in stressed cells. In this study we show that IL-6 has no direct effect on HSP70 expression at 37 degrees C but does augment HSP70 expression in response to heat. IL-6 treatment decreased active MAPK/pERK and glycogen synthase kinase 3beta (GSK3beta) expression and GSK3beta kinase activity. In IL-6-treated cells, monomeric HSF-1 accumulated in the cytoplasm and nucleus, bound DNA but was transcriptionally inactive. On exposure to heat shock this modified monomer assumed the transcriptionally active phenotype with trimerization and hyperphosphorylation evident. The increased induction of HSP70 in IL-6 and heat treated cells was inhibited using PI3-kinase inhibitors or Akt inhibition and was HSF-1 dependent. IL-6, via the PI3-kinase/Akt pathway leads to inhibition of the repressive kinases MAPK/pERK and GSK3beta, and this converts inactive HSF-1 to an intermediate DNA-binding form augmenting transcriptional activation in the presence of a second stressor. PMID- 17273790 TI - Overexpression of the opioid growth factor receptor downregulates cell proliferation of human squamous carcinoma cells of the head and neck. AB - The opioid growth factor (OGF) is a constitutively expressed negative growth regulator whose action is mediated by the OGF receptor (OGFr). The OGF-OGFr axis tonically regulates the growth of human squamous cell carcinoma of the head and neck (SCCHN). To examine the repercussions of amplifying OGFr in SCCHN, constructs were prepared to overexpress OGFr in SCC-1 cells; six clonal lines were examined. OGFr binding assays of clonal cells revealed a 2.4- to 8.4-fold increase in binding capacity compared to wild-type (WT) and empty vector (EV) controls; binding affinity was comparable in all groups. OGFr protein expression, as measured by quantitative immunohistochemistry and Western blotting, was increased in clonal cell lines compared to controls. Under standard growth conditions the cell number of the OGFr clonal lines was reduced by 11 to 68% from the WT group, and doubling times were 7 to 67% longer. Addition of exogenous OGF further reduced (8 to 37%) cell growth of the clonal lines. Depletion of endogenous OGF with antibodies to this peptide increased growth 2-fold in cells amplifying OGFr relative to increases of 32 and 34% for the WT and EV groups, respectively. DNA synthesis of cells overexpressing OGFr was reduced from the WT group by 46 to 75%. These data indicate that the OGF receptor is integral to cell replication of SCCHN, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias. PMID- 17273791 TI - The breakpoint identified in a balanced de novo translocation t(7;9)(p14.1;q31.3) disrupts the A-kinase (PRKA) anchor protein 2 gene (AKAP2) on chromosome 9 in a patient with Kallmann syndrome and bone anomalies. AB - We report the molecular characterization of a patient with Kallmann syndrome and bone anomalies bearing a balanced de novo translocation t(7;9)(p14.1;q31.3) which completely disrupts the A-kinase anchor protein 2 gene (AKAP2) on chromosome 9. In order to investigate the role of AKAP2 in the pathogenesis of the disease, we analyzed the expression of Akap2 in mouse embryos. The expression pattern was consistent with the phenotype observed and mAkap2 was actually found in the olfactory bulb and in the cartilagineous structures of the embryo. Since AKAP2 is supposed to bind and compartmentalize the PKA, we also analyzed the distribution and quantity of PKA in limphoblastoid cell lines of the patient compared with a control; these experiments did not demonstrate any differences between the cell lines. Furthermore a collection of 98 DNA samples from sporadic Kallmann patients was screened for mutations in this gene. The analysis revealed two different sequence variations observed in two patients but not in 200 control chromosomes: since they have been detected also in the unaffected mother of one of the two patients we can assume that they are rare polymorphisms, although we cannot exclude that they represent mutations with incomplete penetrance. Our findings suggest that the complex phenotype with Kallmann syndrome and bone anomalies observed in our patient could be the result of the interruption of the AKAP2 gene. However, a position effect mediated by the translocation could not be excluded. The screening of AKAP2 in other Kallmann patients will be necessary to elucidate its role in the pathogenesis of the disease. PMID- 17273792 TI - New aspects of chromosomal evolution in the gorilla and the orangutan. AB - It is well-accepted that studies of chromosomal changes which have occurred during the evolution of the great apes and the human provide clues towards the phylogeny of these species. Applying recently developed molecular cytogenetic approaches, this study on the chromosomes of the orangutan and the gorilla revealed the presence of cryptic, until now, unrecognized cytogenetic rearrangements mainly within the evolutionary dynamic subcentromeric and subtelomeric regions. On four orangutan chromosomes new rearrangements were detected such as a pericentric inversion in Pongo pygmaeus abeli (PPYa) #1, complex rearrangements on #2 of Pongo pygmaeus pygmaeus (PPYp) and PPYa and a subtelomeric deletion on PPYa&p #19. Additionally, the first centromere repositioning in the great apes was detected on PPYa&p #8. Moreover, the breakpoints of four pericentric inversions within the two orangutan subspecies and three pericentric inversions on Gorilla beringei beringei (GBEb) chromosomes #3, #11 and #13 were refined. The new molecular cytogenetic findings are discussed and compared with the available literature. PMID- 17273793 TI - Sonic hedgehog inversely regulates the expression of angiopoietin-1 and angiopoietin-2 in fibroblasts. AB - Nerves and blood vessels have similar branching patterns and use common morphogenic molecules during development. Recent studies show that sonic hedgehog (Shh), a traditional neurogenic morphogen, is required for embryonic arterial differentiation and can induce angiogenesis. We investigated whether Shh regulates the expression of angiogenic factors. Using NIH3T3 embryonic fibroblast cells, we demonstrated that Shh increased the mRNA levels of angiopoietin-1 (Ang 1), a secreted ligand that regulates endothelial interaction with mural cells (pericytes and smooth muscle cells) and promotes blood vessel maturation. In contrast, Shh decreased mRNA levels of angiopoietin-2 (Ang-2), a negative modulator of Ang-1. By contrast, Shh did not change the expression of vascular endothelial growth factor (VEGF) mRNA, a potent endothelial mitogen. The effect of Shh appeared to be cell-type specific as the addition of Shh to neural progenitor cells or neurons did not alter Ang-1, Ang-2 or VEGF mRNA levels. The addition of cyclopamine, an inhibitor of Shh signaling, to NIH3T3 cells, suppressed the regulation of Ang-1 and Ang-2 mRNA levels in the presence of Shh. Collectively, our results suggest that Shh may contribute to blood vessel growth, maturation and stabilization in a neurovascular network by reciprocally regulating the vascular morphogens Ang-1 and Ang-2 in a cell-type-specific manner. PMID- 17273794 TI - Establishment and characterization of Asian oral cancer cell lines as in vitro models to study a disease prevalent in Asia. AB - We have established 3 cell lines ORL-48, -115 and -136 from surgically resected specimens obtained from untreated primary human oral squamous cell carcinomas of the oral cavity. The in vitro growth characteristics, epithelial origin, in vitro anchorage independency, human papilloma-virus (HPV) infection, microsatellite instability status, karyotype and the status of various cell cycle regulators and gatekeepers of these cell lines were investigated. All 3 cell lines grew as monolayers with doubling times ranging between 26.4 and 40.8 h and were immortal. Karyotyping confirmed that these cell lines were of human origin with multiple random losses and gains of entire chromosomes and regions of chromosomes. Immunohistochemistry staining of cytokeratins confirmed the epithelial origin of these cell lines, and the low degree of anchorage independency expressed by these cell lines suggests non-transformed phenotypes. Genetic analysis identified mutations in the p53 gene in all cell lines and hypermethylation of p16INK4a in ORL-48 and -136. Analysis of MDM2 and EGFR expression indicated MDM2 overexpression in ORL-48 and EGFR overexpression in ORL-136 in comparison to the protein levels in normal oral keratinocytes. Analysis of the BAT-26 polyadenine repeat sequence and MLH-1 and MSH-2 repair enzymes demonstrated that all 3 cell lines were microsatellite stable. The role of HPV in driving carcinogenesis in these tumours was negated by the absence of HPV. Finally, analysis of the tissues from which these cell lines were derived indicated that the cell lines were genetically representative of the tumours, and, therefore, are useful tools in the understanding of the molecular changes associated with oral cancers. PMID- 17273795 TI - Analysis of differentially expressed genes in early- and late-stage APPsw transgenic and normal mice using cDNA microarray. AB - The complexity of Alzheimer's disease (AD) has made it difficult to examine its underlying mechanism. A gene microarray offers a solution to the complexity through a parallel analysis of most of the genes expressed in the brains from AD transgenic mice. In our previous study, a total of 52 differentially expressed genes were identified in 18-month-old APPsw-transgenic mice compared to age matched normal mice. We extended our work to better understand the relevant gene profiles from both early- and late-stage transgenic and normal mice. To accomplish this, cDNA microarray was used with the large-scale screening of the brain mRNA from transgenic and normal mice of 1 and 18 months of age. We identified a total of 48 genes, 6 up-regulated and 42 down-regulated, differentially expressed with a significant degree of induction and reduction in the brains from moderate 18-month-old transgenic mice compared to 1-month-old transgenic mice. In parallel, a total of 40 differentially expressed genes, 6 up regulated and 34 down-regulated, were also found in the brains from moderate 18 month-old normal mice compared to 1-month-old normal mice. Thus, differentially expressed genes upon APPsw overexpression and the aging process are useful targets through which investigators can choose genes of particular interest. In the future, it will be necessary to study the function of differentially expressed genes, which are targets for developing drugs, using pharmacoproteomics. PMID- 17273796 TI - Curcumin attenuates the expression of IL-1beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB and MAPKs as potential upstream targets. AB - TNF-alpha induces some proinflammatory cytokines including IL-1beta, IL-6, IL-8, and itself by activation of NF-kappaB or MAPKs (p38, JNK, ERK). These cytokines play important roles in various inflammatory skin diseases, such as psoriasis. Recently it was also reported that expression of cyclin E is up-regulated by ERK pathway after TNF-alpha treatment. However, it was unknown whether curcumin, showing inhibitory effects on NF-kappaB and MAPKs, attenuates the expression of TNF-alpha-induced IL-1beta, IL-6, IL-8, and TNF-alpha as well as cyclin E expression in HaCaT cells. In this study, we investigated the inhibitory effect of curcumin on expression of proinflammatory cytokines and cyclin E in TNF-alpha treated HaCaT cells. We found that curcumin inhibited the expression of TNF-alpha induced IL-1beta, IL-6, and TNF-alpha, but not IL-8, in TNF-alpha-treated HaCaT cells as well as the TNF-alpha-induced cyclin E expression. In addition, curcumin inhibited the activation of MAPKs (JNK, p38 MAPK, and ERK) and NF-kappaB in TNF alpha-treated HaCaT cells. Taken together, curcumin exerts anti-inflammatory and growth inhibitory effects in TNF-alpha-treated HaCaT cells through inhibition of NF-kappaB and MAPK pathways. PMID- 17273798 TI - Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand. AB - The use of radionuclide molecular imaging enables the selection of patients for treatment using molecular medicine. Preclinical studies have demonstrated that a novel low-molecular-weight affinity ligand, Affibody molecule Z(HER2:342) can image the expression of HER2 with high sensitivity and specificity in tumour xenografts and has a potential for the selection of patients for treatment using Herceptin or other anti-HER2 medicine. In this study, we performed a comparative evaluation of two possible linkers for radioiodination of the Affibody molecule Z(HER2:342), 4-iodobenzoate (PIB) and [4-isothiocyanatobenzyl)-amino]-undecahydro closo-dodecaborate (DABI). It was shown that the use of DABI makes it possible to obtain radioiodinated Z(HER2:342) with preserved capacity for selective binding to HER2-expressing cells. There was no difference between 125I-PIB-Z(HER2:342) and 125I-DABI-Z(HER2:342) in cellular retention of radioactivity after interrupted incubation with radiolabelled Affibody ligands. In vivo, the biodistribution of 125I-PIB-Z(HER2:342) was characterized by a high tumour uptake at 4 h pi (12.7+/-4.6% IA/g) and a quick clearance from blood and normal organs. The tumour uptake of 125I-DABI-Z(HER2:342) was appreciably lower (2.7+/-1.2% IA/g), and a high uptake of this conjugate in the liver was observed. A gamma camera experiment (at 6 h pi) demonstrated that the use of 125I-PIB-Z(HER2:342) provided a much better contrast of imaging HER2-expressing xenografts than the use of 125I-DABI-Z(HER2:342). In conclusion, 125I-PIB-Z(HER2:342) is superior to 125I-DABI-Z(HER2:342) as an agent for imaging HER2 expression in vivo. PMID- 17273797 TI - GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress. AB - Cells regulate the rate of protein synthesis during conditions of cell stress to adapt to environmental changes. However, the molecular interactions between signaling pathways controlling translation and the cellular response to stress remain to be elucidated. Here, we show that the expression of growth arrest and DNA damage protein 34 (GADD34) is induced by energy depletion and that the expression of this protein protects cells from apoptotic cell death. During conditions of cell stress, GADD34 forms a stable complex with tuberous sclerosis complex (TSC) 1/2, causes TSC2 dephosphorylation, and inhibits signaling by mammalian target of the rapamycin (mTOR). These findings demonstrate that crosstalk between GADD34 and the mTOR signaling pathways contributes to the response of the protein synthetic machinery to environmental stress. GADD34 may find clinical potential as a target drug for the treatment of mTOR-associated diseases. PMID- 17273799 TI - FDG-PET and CT features of non-small cell lung cancer based on tumor type. AB - We determined if specific tumor types of non-small cell lung cancer can be identified by variance in FDG-PET standard uptake value (SUV) in combination with characteristics on CT. Staging FDG-PET and CT scans of 81 patients (34 men and 47 women, average age 67+/-11 years) with 82 lung cancers were analyzed. Mean tumor SUV was calculated at the location of maximum FDG uptake. Tumor size, margins, and location were analyzed on CT. Statistical analysis compared SUV between tumor subtypes, assessed relationship between tumor subtype and features on CT and determined if combination of CT and SUV patterns predicted tumor type. In total 35 adenocarcinomas (AC); 15 bronchioloalveolar cell carcinomas (BAC), 23 squamous cell carcinomas and 9 large cell carcinomas were evaluated. Significant differences were found between SUV of all AC and squamous cell (p<0.0001); between all AC and large cell (p=0.03); between non-BAC AC and squamous cell types (p=0.0005); BAC and non-BAC AC (p=0.04), BAC and squamous cell (p<0.0001); BAC and large cell (p=0.004). Ground glass was the most significant CT feature in distinguishing tumor types, which was seen in BAC (p<0.0003). In conclusion, SUVs for non-small cell lung cancer were most significantly different between BAC and all other NCLC cell subtypes. The presence of ground glass in a nodule on CT is a significant feature for BAC and should raise the suspicion for this tumor type despite low FDG uptake. PMID- 17273800 TI - Cloning of a rat-specific long PCP4/PEP19 isoform. AB - We report the identification of a cDNA that encodes a putative protein of 94 amino acids and expected molecular weight of 10.7 kDa, the C-terminal half of which is identical to that of PEP19, a small, brain-specific protein involved in Ca++/calmodulin signaling. The novel rat-specific protein, tentatively named long PEP19 isoform (LPI), is the product of alternative splicing of the rat PCP4 gene encoding PEP19. We found that antibodies raised against the first 13 N-terminal amino acids of LPI, not present in PEP19, recognize a protein enriched in the developing rat brain. PMID- 17273801 TI - Evidence for a paracrine role of endogenous adrenomedullary galanin in the regulation of glucocorticoid secretion in the rat adrenal gland. AB - Previous investigations have shown that rat adrenocortical cells are provided with galanin receptors, and galanin stimulates glucocorticoid secretion from dispersed cells. The present study aimed to clarify the possible role of galanin in the physiological regulation of rat adrenal secretory activity. Reverse transcription-polymerase chain reaction detected galanin mRNA expression in the adrenal medulla, but not in the cortex. Sizeable concentrations of galanin immunoreactivity were measured by radioimmune assay only in the adrenomedullary tissue. Galanin raised norepinephrine, but not epinephrine, release from adrenomedullary tissue. Galanin immunoneutralization (obtained with concentrations of anti-galanin antibody able to block the galanin glucocorticoid secretagogue effect on dispersed adrenocortical cells) decreased basal corticosterone production from adrenal slices containing adrenomedullary tissue, without affecting that from dispersed adrenocortical cells. The beta-adrenoceptor antagonist l-alprenolol partially prevented galanin-stimulated corticosterone secretion from adrenal slices, without per se altering basal secretion. Taken together, our findings allow us to conclude that endogenous galanin, produced in adrenal medulla, is involved in the regulation of adrenocortical glucocorticoid secretion acting via a two-fold paracrine mechanism: i) direct activation of adrenocortical galanin receptors; and ii) stimulation of adrenomedullary release of catecholamines, which in turn activate beta-adrenoceptors located on adrenocortical cells. PMID- 17273802 TI - Alpha-synuclein and tyrosine hydroxylase expression in acute rotenone toxicity. AB - Chronic low-dose (2-3 mg/kg/day) rotenone infusion produces clinical features and biological markers of Parkinson's disease (PD) in some rats. A significant proportion of rats, however, die of acute rotenone toxicity. Most studies have focused on chronic rotenone-infused rats. It has not been established if the animals that die of acute low-dose rotenone toxicity manifest clinical or pathological evidence of PD. In the present study, six rats that received continuous 3 mg/kg/day subcutaneous rotenone infusion, became moribund and were euthanized after five days were compared with ten vehicle infused animals sacrificed 14, 28 or 56 days after placebo infusion. All rotenone-infused rats had significant motor function decline beginning one day after the infusion and progressive worsening in the physical condition until they became severely akinetic, at which point they were euthanized. In the substantia nigra of rotenone-treated rats, four of six had reduced numbers of tyrosine hydroxylase positive neurons and all six had increased nigral alpha-synuclein expression. Our observations show that even a short duration of low-dose subcutaneous rotenone infusion can induce clinical and pathological markers of PD in some rats. The pathophysiology of the enhanced susceptibility to PD in some animals remains to be established. PMID- 17273803 TI - Fatty acid content and pattern of spleen phospholipids and triglycerides in normal and either type-1 or type-2 diabetic rats. AB - The fatty acid pattern of spleen phospholipids and triglycerides was examined in fed or overnight fasted normal rats, streptozotocin-induced diabetic animals (type-1 diabetes) and Goto-Kakizaki rats (type-2 diabetes). In both phospholipids and triglycerides, differences were observed in the relative contribution of several fatty acids, as well as in the ratio between distinct fatty acids, when comparing fed to fasted rats, normal to diabetic animals and male to female Goto Kakizaki rats. Diabetes increased to a greater extent the C22:6omega3 content of phospholipids in the spleen than in either the liver or the brain. However, the diabetes-induced changes in the C22:6omega3 content of triglycerides was closely comparable in the spleen, liver and brain. These findings suggest that the incorporation of fatty acids into triglycerides is controlled by comparable regulatory factor(s), e.g. insulinemia, in the spleen, liver and brain. In the case of phospholipids, however, an apparent adaptation to diabetic stress was more marked in the spleen than in the liver, and virtually absent in the brain. The proposed dichotomy in the environmental regulation of fatty acid synthesis and incorporation into phospholipids and triglycerides was further supported by distinct diabetes-related changes in the apparent activity of Delta9-desaturase in these two classes of lipids. PMID- 17273804 TI - Comparative integromics on FZD7 orthologs: conserved binding sites for PU.1, SP1, CCAAT-box and TCF/LEF/SOX transcription factors within 5'-promoter region of mammalian FZD7 orthologs. AB - Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate MYC, CCND1, FGF20, JAG1, WISP1 and DKK1 genes, while non-canonical WNT signals are transduced through FZD family receptor and PTK7/ROR2/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NFAT and NLK signaling cascades. FZD7, expressed in the normal gastrointestinal tract, is upregulated in esophageal cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma. Here, chimpanzee FZD7 and cow Fzd7 genes were identified and characterized by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD7 and cow Fzd7 genes were identified within NW_001232110.1 and AC173037.2 genome sequences, respectively. Chimpanzee FZD7 and cow Fzd7 showed 100% and 97.2% total-amino-acid identity with human FZD7. All of the nine amino-acid residues substituted between human FZD7 and human FzE3 were identical to those of human FZD7 in chimpanzee, cow, mouse and rat FZD7 orthologs. Functional analyses using FzE3 with multiple cloning artifacts and/or sequencing errors are invalid. FZD7 orthologs were seven-transmembrane proteins with extracellular Frizzled domain, leucine zipper motif around the 5th transmembrane domain, and cytoplasmic DVL- and PDZ-binding motifs. Ser550 and Ser556 of FZD7 orthologs were putative aPKC phosphorylation sites. Dimerization and Ser550/556 phosphorylation were predicted as regulatory mechanisms for the signaling through FZD7. Transcriptional start site of human FZD7 gene was 735-bp upstream of NM_003507.1 RefSeq 5'-end. In addition to gastrointestinal cancer, hepatocellular cancer and pancreatic cancer, human FZD7 mRNAs were expressed in blastocysts, undifferentiated embryonic stem (ES) cells, ES-derived endodermal progenitors, ES-derived neural progenitors, fetal cochlea, retinal pigment epithelium, olfactory epithelium, regenerating liver, and multiple sclerosis. Comparative genomics analyses revealed that the binding sites for PU.1, SP1/Kruppel-like, CCAAT-box, and TCF/LEF/SOX transcription factors were conserved among 5'-promoter regions of mammalian FZD7 orthologs. PMID- 17273805 TI - Inhibitory effect of Artemisia capillaris extract on cytokine-induced nitric oxide formation and cytotoxicity of RINm5F cells. AB - Cytokines produced by immune cells infiltrating pancreatic islets are important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. Cytokines stimulate an inducible form of nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, leading to insulin insufficiency. In the present study, the effects of Artemisia capillaris extract (ACE) on cytokine induced beta-cell damage were examined. Treatment of RINm5F (RIN) rat insulinoma cells with interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) induced cell damage. ACE completely protected IL-1beta and IFN-gamma-mediated cytotoxicity in a concentration-dependent manner. Incubation with ACE resulted in a significant reduction in IL-1beta and IFN-gamma-induced NO production, a finding that correlated well with reduced levels of the iNOS mRNA and protein. The molecular mechanism by which ACE inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation. The IL-1beta and IFN-gamma stimulated RIN cells showed increases in NF-kappaB binding activity and p65 subunit levels in the nucleus, and IkappaBalpha degradation in cytosol compared to unstimulated cells. Furthermore, ACE restored the cytokine-induced inhibition of insulin release from isolated islets. These results suggest that ACE protects beta-cells by suppressing NF-kappaB activation. PMID- 17273806 TI - Hallmarks of protein oxidative damage in neurodegenerative diseases: focus on Alzheimer's disease. AB - The pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, has been linked to a condition of oxidative and nitrosative stress, arising from the imbalance between increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and antioxidant defences or efficiency of repair or removal systems. The effects of free radicals are expressed by the accumulation of oxidative damage to biomolecules: nucleic acids, lipids and proteins. In this review we focused our attention on the large body of evidence of oxidative damage to protein in Alzheimer's disease brain and peripheral cells as well as in their role in signalling pathways. The progress in the understanding of the molecular alterations underlying Alzheimer's disease will be useful in developing successful preventive and therapeutic strategies, since available drugs can only temporarily stabilize the disease, but are not able to block the neurodegenerative process. PMID- 17273807 TI - Features associated with the non-participation and drop out by socially-at-risk children and adolescents in mental-health epidemiological studies. AB - OBJECTIVE: To study socio-demographic and functional features related with non collaboration in a longitudinal design of mental health within a high-risk population of individuals 9 and 13 years old. METHOD: Regression analyses were used to assess factors affecting the decision to decline participation, and what characteristics both of children and families increase the probability of dropping out once the study had already started. RESULTS: Refusal of participation at the outset is more probable for lower socioeconomic groups, unemployed families (or with Social Security benefits), minority cultures and children having low school performance. The risk of participants dropping out is higher for adolescents, those who need help at school, are unhealthy, have more life-events, receive professional help for mental problems or have had more psychopathology in previous assessments. Lengthy interviews or evaluations without the return of reports to families are also predictive of drop out. CONCLUSIONS: This study has practical implications for reducing the lack of collaboration in the prospective studies that assess mental health in children and adolescents. Improvement in the estimation of epidemiological indices requires the planning of special measures for research projects carried out on populations with fewer resources so as to recruit individuals with lower SES, adolescents, individuals with pathologies (physical or psychological) and those with lower levels of school achievement. PMID- 17273808 TI - Quality Assessment in Multiple Sclerosis Therapy (QUASIMS): a comparison of interferon beta therapies for relapsing-remitting multiple sclerosis. AB - Interferon beta (IFN beta) preparations are the most frequently prescribed therapies for patients with relapsing multiple sclerosis (MS). Several open-label observational studies report similar efficacy among IFN beta preparations. The Quality Assessment in Multiple Sclerosis Therapy (QUASIMS) study is a large, open label observational study designed to compare the effectiveness and tolerability of available IFN beta preparations as disease-modifying therapies for relapsing MS across a wide range of clinical practice settings. This retrospective, controlled cohort study was conducted by chart review at 510 sites in Germany, Austria, and Switzerland. Enrolled patients had received one of the four available IFN beta preparations/dosing regimens (intramuscular IFN beta-1a 30 microg 1x/week [Avonex], subcutaneous (SC) IFN beta-1a 22 or 44 microg 3 x/week [Rebif], or SC IFN beta-1b 250 microg 3.5x/week [Betaferon/Betaseron]) for >or= 2 years. Pre-planned outcomes at 1 and 2 years included change from baseline Expanded Disability Status Scale (EDSS) score, percentage of progression-free patients (< 1.0 EDSS point), annualised relapse rate (RR), percentage of relapse free patients, and reasons for therapy change. Of 4754 evaluable patients, 3991 (84%) received IFN beta as initial therapy. There were no significant differences among IFN betas when used as initial or follow-up therapy on almost all outcome variables. Relapse rate was consistently higher and percentage of relapse-free patients consistently lower for all products used as follow-up versus initial therapy. Results of QUASIMS showed similar effectiveness among IFN beta products. Benefits were consistently superior when IFN beta was used as initial rather than follow-up therapy. Our results suggest that patients do not benefit in terms of disease outcome from switching between IFN beta preparations/dosing regimens. PMID- 17273809 TI - Systematic assessment of the tagging polymorphisms of the COL1A1 gene for high myopia. AB - Reduced scleral collagen accumulation has been found in the development of myopia. Single nucleotide polymorphisms (SNPs) at the type I collagen alpha-1 gene (COL1A1) may cause different susceptibilities to myopia. We conducted a case control study to systematically examine COL1A1 as a candidate gene for high myopia. A case was defined as spherical refraction or=-1.5 D. The study comprised 471 cases and 623 controls, and ten tagging SNPs were genotyped. None of the SNPs reached the significant level of 0.05. Subset analysis on cases with a strong family history did not demonstrate significant results. We could not find an interaction between gene and near work. Exploratory analyses by changing the cutoff values to re-define cases and controls did not improve the results. Haplotype analysis did not yield significant association with myopia. This study failed to demonstrate COL1A1 as a significant risk factor for high myopia. PMID- 17273810 TI - Atherosclerosis and inflammation: insights from rheumatoid arthritis. AB - Cardiovascular disease is a major health care problem and the most common cause of death among individuals from developed nations. Our understanding of atherosclerosis has evolved from a passive process resulting in narrowing of the lumen and consequent myocardial ischemia to a dynamic process that involves inflammation. The study of atherosclerosis in patients with chronic inflammation, such as rheumatoid arthritis (RA), will provide insights into the relationship between inflammation and atherosclerosis. We review the relationship between atherosclerosis and inflammation within the context of RA, providing evidence that patients with RA have increased cardiovascular morbidity and mortality and accelerated coronary and extra-coronary atherosclerosis. In addition, traditional and novel cardiovascular risk factors are discussed. Finally, actions that a rheumatologist can take to better control this cardiovascular morbidity are suggested. These can be summarized as follows: (1) careful assessment and treatment of cardiovascular risk, (2) better control of inflammation, and (3) individual risk-benefit evaluation of need for cyclo-oxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs, and high doses of corticosteroids. PMID- 17273811 TI - No effects of adalimumab therapy on the activation of NF-kappaB in lymphocytes from patients with severe rheumatoid arthritis. AB - The aim of this study was to determine the activation level of the pro inflammatory transcription factor nuclear factor kappaB (NF-kappaB) in lymphocytes of patients with rheumatoid arthritis (RA) before and during an anti tumor necrosis factor alpha (TNFalpha) therapy (adalimumab). In addition, we analyzed the inflammatory markers, interleukin 6 (IL-6), and C-reactive protein (CRP) and investigated the expression of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies in patients' sera. Twenty RA patients and 20 control subjects were investigated. RA patients' characteristics were evaluated by radiography and disease activity score 28 (DAS 28). Twelve weeks of adalimumab therapy was effective in the treatment of RA patients, as shown by a significant improvement of the DAS 28. The inflammatory markers IL-6 and CRP were significantly different in sera of RA patients compared to the control group before the onset of therapy and exhibited a tendency to return to normal levels during the first 12 weeks of therapy. We measured a comparable activation level of NF-kappaB in lymphocytes of control subjects and of RA patients before starting adalimumab therapy. During the following 12 weeks, no significant changes in the activation levels of both NF-kappaB subunits were detected. Serum concentration of RF was significantly lower after 12 weeks, whereas anti-CCP antibody level remained constant. PMID- 17273812 TI - Diagnosis of plant-thorn synovitis by high-resolution ultrasonography: a case report and literature review. AB - Plant-thorn synovitis is an uncommon cause of arthritis and has not been reported in Asian countries. Zanthoxylum ailanthoides, an aromatic plant distributed in East Asia, is used as a spice in Taiwan. We reported a case of acute monoarthritis over the third metacarpo-phalangeal joint of the right hand after an injury by the thorn of the Zanthoxylum ailanthoides. A thorn foreign body of 2.7 mm in length was detected in the joint by high-resolution ultrasonography and led to a surgical synovectomy. The patient recovered completely after synovectomy. Plant-thorn synovitis is easily negligible. Early diagnosis is difficult and frequently delayed. The removal of thorn by synovectomy is the only curative treatment for plant-thorn synovitis. Compared to CT and MRI, ultrasonography is inexpensive, nonradioactive, repeatable, and easily accessible. It could detect foreign bodies that are smaller than 0.5 mm. High resolution ultrasonography is a useful tool for detecting plant thorn and could promote early diagnosis. PMID- 17273813 TI - Size and location of the fetal diaphragm during the fetal period in human fetuses. AB - AIM: The aim of this study was to determine the development and the size and localization of the diaphragm during the fetal period in human fetuses. MATERIALS AND METHODS: One hundred and eighty-four diaphragm obtained from human fetuses aged between 9 and 40 weeks of gestation was used in this study. The localization of the diaphragm with respect to abdominal cavity and the level of costodiaphragmatic recess with respect to the ribs were determined. The dimensions (height, width, and depth) of the diaphragm were measured. The diameter and localization of apertures on the diaphragm were determined. RESULTS: During the fetal period, the costodiaphragmatic recess was most commonly located at the level of the 9th rib. Means and standard deviations of the all parameters with respect to gestational weeks and months were calculated. No significant differences were observed between sexes for any of the parameters (P > 0.05). All parameters were increasing with age during fetal period. There was significant correlation between gestational age and all parameters (P < 0.001). The localizations of the diaphragmatic apertures did not change throughout the fetal period and aortic hiatus and oesophageal hiatus were most frequently situated to the left of the median plane. CONCLUSION: New data are derived for human fetuses to evaluate diaphragmatic development. Data acquired in this study are believed to contribute to studies of obstetrics, perinatology, forensic medicine and fetal pathology on fetal development of the diaphragm, and diagnosis of its anomalies, pathologies and variations. PMID- 17273814 TI - Pulsed radiofrequency for the treatment of chronic ilioinguinal neuropathy. AB - BACKGROUND: Ilioinguinal neuropathy is a rare but disabling condition. The condition may arise spontaneously or in the setting of pelvic surgery. To date, most therapeutic options have been limited to neuropathic pain medications, anti inflammatory medications, nerve blocks with local anesthetics, or neurectomy. Long-term results of non-surgical interventions are fair at best. We present a case of chronic ilioinguinal neuropathy treated with pulsed radiofrequency. OBJECTIVE: To examine the efficacy of pulsed radiofrequency (PRF) lesioning on pain in ilioinguinal neuropathy. METHOD: A 58-year old man with chronic ilioinguinal neuropathy was treated with PRF and was followed for 3 months. RESULTS: The patient had significant pain relief at 3 months follow up. CONCLUSION: Pulsed radiofrequency lesioning may be a good treatment for chronic ilioinguinal neuropathy in cases refractory to conservative management. PMID- 17273815 TI - Comparison of prosthetic mesh repair and tissue repair in the emergency management of incarcerated para-umbilical hernia: a prospective randomized study. AB - BACKGROUND: Although prosthetic repair has become the gold standard for elective management of para-umbilical hernia (PUH) its use in the setting of acute incarceration is still limited for fear of prosthetic-related complications, mainly infection. The objective of this study was to compare results from prosthetic repair and tissue repair in the management of the acutely incarcerated PUH. PATIENTS AND METHODS: Forty-two patients were prospectively randomized to either the prosthetic-repair group (group 1 = 21 patients) or the tissue-repair group (group 2 = 21 patients). In group 1, an onlay polypropylene mesh was inserted and the presence of non-viable intestine was not considered a contraindication for mesh repair. Operative time, postoperative hospital stay, and postoperative complications were recorded. Follow-up was performed by physical examination to detect recurrence. RESULTS: Mean operative time was significantly longer for group 1 (96.9 +/- 14.6 compared with 65.5 +/- 14.6 min for group 2, P < 0.05). Postoperative hospital stay did not differ significantly between the groups (3 +/- 1.6 compared with 3.5 +/- 2.2 days for groups 1 and 2, respectively). Postoperative complications did not differ significantly between the groups (28.6 vs. 23.8% for groups 1 and 2, respectively). No mesh had to be removed. At follow-up (mean 16 +/- 5.5 months) there were four recurrences in group 2 (4/21, 19%) and no recurrences in group 1 (P < 0.05). CONCLUSION: Use of prosthetic repair for emergency management of incarcerated PUH is safe and leads to superior results, in terms of recurrence, compared with conventional tissue repair. The presence of non-viable intestine cannot, furthermore, be regarded as a contraindication for prosthetic repair. PMID- 17273816 TI - Utility of computed tomographic colonography in surveillance for hereditary nonpolyposis colorectal cancer syndrome. AB - Computed tomographic colonography (CTC) is suggested to be an alternative to colonoscopy as a surveillance tool in subjects with a high risk for colorectal cancer (CRC). To evaluate the utility of CTC we successively examined 78 subjects, all with a DNA mismatch repair gene mutation, by CTC and colonoscopy. We detected altogether 37 polyps or tumors in 28 subjects (prevalence 35.9%), adenomas in 13 subjects (16.7%), CRC in two (2.6%), and hyperplastic polyps in 13 (16.7%). A great majority of the polyps were diminutive. The per-patient sensitivity for detecting all lesions with CTC was 0.25 and 0.29 by two radiologists and the specificities 0.82 and 0.76. For lesions of 10 mm or larger the sensitivities were 0.6 and 1.0 and the specificities 0.96 by each examiner. Each diagnosed the two cancers correctly. We concluded that CTC has an acceptable accuracy for large lesions in the colon but the detection rate for small polyps is not comparable to that in colonoscopy. Therefore CTC remains a second choice in surveillance for use when colonoscopy for some reason is incomplete or unsuitable. PMID- 17273817 TI - Purification and characterization of rhodobactin: a mixed ligand siderophore from Rhodococcus rhodochrous strain OFS. AB - The siderophore produced by Rhodococcus rhodochrous strain OFS, rhodobactin, was isolated from iron-deficient cultures and purified by a combination of XAD-7 absorptive/partition resin column and semi-preparative HPLC. The siderophore structure was characterized using 1D and 2D (1)H, (13)C and (15)N NMR techniques (DQFCOSY, TOCSY, NOESY, HSQC and LR-HSQC) and was confirmed using ESI-MS and MS/MS experiments. The structural characterization revealed that the siderophore, rhodobactin, is a mixed ligand hexadentate siderophore with two catecholate and one hydroxamate moieties for iron chelation. We further investigated the effects of Fe concentrations on siderophore production and found that Fe limiting conditions (Fe concentrations from 0.1 microM to 2.0 microM) facilitated siderophore excretion. Our interests lie in the role that siderophores may have in binding metals at mixed contamination sites (containing metals/radionuclides and organics). Given the broad metabolic capacity of this microbe and its Fe scavenging ability, R. rhodochrous OFS may have a competitive advantage over other organisms employed in bioremediation. PMID- 17273818 TI - Regulation of systemic iron homeostasis: how the body responds to changes in iron demand. AB - The iron that is required to meet the metabolic needs of cells and tissues is derived from the plasma. Plasma iron in turn reflects the release of iron from various body cells, principally the macrophages of the reticuloendothelial system, and the absorption of dietary iron by the proximal small intestine. This iron donation is highly regulated and the liver-derived peptide hepcidin has emerged as the key modulator of cellular iron export. Following its synthesis and secretion from the liver, circulating hepcidin reduces iron export into the plasma by binding to the iron efflux protein ferroportin1 on the surface of enterocytes, macrophages and other cell types and causing its internalization. The level of hepatic hepcidin expression is influenced by HFE, transferrin receptor 2 and hemojuvelin, and the signal transduction pathway(s) linking these proteins to hepcidin are only beginning to be revealed. Hemojuvelin has recently been shown to signal through the bone morphogenetic protein pathway, ultimately activating receptor SMAD/SMAD4 complexes to alter hepcidin transcription. Circulating differic transferrin has emerged as a possible upstream regulator of the liver-based hepcidin regulatory pathway. In addition to being regulated by body iron requirements, hepcidin expression can be modulated by pro-inflammatory cytokines such as interleukin-6. The continuing analysis of inherited disorders of iron metabolism combined with biochemical analysis of signal transduction pathways is essential to fully define this important regulatory system. PMID- 17273819 TI - Cyclic GMP in blood and minimal hepatic encephalopathy: fine-tuning of the diagnosis. PMID- 17273820 TI - [Value of vascular ultrasound in the evaluation of hemodialysis fistulas]. AB - Vascular ultrasound has been proven to be effective in the assessment of hemodialysis fistulas providing noninvasive diagnostic work-up of vascular morphology and hemodynamics. The most common reason for hemodialysis fistula failure is thrombosis due to stenosis. Therefore, early identification of stenosis is essential to avoid complications. Ultrasound-based identification of hypoechoic plaques and intimal proliferation helps to reach therapeutic decisions. An estimation of the grade of stenosis is also feasible. An occlusion rate of up to 45% due to reduced blood flow justifies follow-up examinations. Due to frequent puncture of the fistula the risk of hemodynamically relevant stenoses is increased. Establishment of new ultrasound methods like B-flow and advanced dynamic flow (ADF) enable direct visualization of the flow in the area of the anastomosis. In addition, high-resolution ultrasound techniques allow improved flow detection without aliasing. Our report addresses the topics of examination strategy, possible complications, and treatment like percutaneous intervention techniques. PMID- 17273821 TI - Cladosporium fulvum CfHNNI1 induces hypersensitive necrosis, defence gene expression and disease resistance in both host and nonhost plants. AB - Nonhost resistance as a durable and broad-spectrum defence strategy is of great potential for agricultural applications. We have previously isolated a cDNA showing homology with genes encoding bZIP transcription factors from tomato leaf mould pathogen Cladosporium fulvum. Upon expression, the cDNA results in necrosis in C. fulvum host tomato and nonhost tobacco plants and is thus named CfHNNI1 (for C . f ulvum host and nonhost plant necrosis inducer 1). In the present study we report the induction of necrosis in a variety of nonhost plant species belonging to three families by the transient in planta expression of CfHNNI1 using virus-based vectors. Additionally, transient expression of CfHNNI1 also induced expression of the HR marker gene LeHSR203 and greatly reduced the accumulation of recombinant Potato virus X. Stable CfHNNI1 transgenic tobacco plants were generated in which the expression of CfHNNI1 is under the control of the pathogen-inducible hsr203J promoter. When infected with the oomycetes pathogen Phytophthora parasitica var. nicotianae, these transgenic plants manifested enhanced expression of CfHNNI1 and subsequent accumulation of CfHNNI1 protein, resulting in high expression of the HSR203J and PR genes, and strong resistance to the pathogen. The CfHNNI1 transgenic plants also exhibited induced resistance to Pseudomonas syringae pv. tabaci and Tobacco mosaic virus. Furthermore, CfHNNI1 was highly expressed and the protein was translocated into plant cells during the incompatible interactions between C. fulvum and host and nonhost plants. Our results demonstrate that CfHNNI1 is a potential general elicitor of hypersensitive response and nonhost resistance. PMID- 17273822 TI - Isolation and molecular characterization of a Spotted leaf 18 mutant by modified activation-tagging in rice. AB - A lesion mimic mutant that we designated Spotted leaf 18 (Spl18) was isolated from 13,000 activation-tagging lines of rice produced by our modified activation tagging vector and further characterized. Spl18 was dominant and its phenotype was linked to the T-DNA insertion. An ORF was located about 500 bp downstream of the inserted T-DNA, and the deduced protein, designated OsAT1, showed sequence similarity to an acyltransferase whose expression is induced by hypersensitive reaction in tobacco. The transcriptional level of OsAT1 was very low in the WT leaf blade but high in Spl18 leaf blade. In wild-type rice, OsAT1 was transcribed mainly in the young panicle, in the panicle just after heading, and in the leaf sheath. In addition, transcription of the genes for PR protein was upregulated in Spl18, accumulation of phytoalexins (both momilactone A and sakuranetin) was increased, and resistance to blast disease was improved. We then combined OsAT1 genomic DNA downstream of the modified 35S promoter and re-transformed it into rice. Lesion mimic and blast resistance phenotypes were detected in the transgenic lines produced, clearly indicating that overexpression of OsAT1 caused the Spl18 phenotypes. In addition, plants overexpressing OsAT1 showed resistance to bacterial blight. PMID- 17273823 TI - Testing the efficacy of RNA interference constructs in Aspergillus fumigatus. AB - We recently developed a silencing vector in Aspergillus fumigatus which carries a hygromycin resistance marker and a transcriptional unit for hairpin RNA expression under the control of the inducible glucoamylase promoter (pGla) (Mouyna et al. in FEMS Microbiol Lett 237:317-324, 2004). We showed previously that this vector can be used for the RNA interference application of two genes ALB1 and FKS1 of which reduced mRNA levels occurred for both, with phenotypic consequences resembling disruptions of genes involved in melanin (ALB1) and beta(1-3)glucan biosynthesis (FKS1). We reported here the silencing of KRE6 and CRH1, two other genes putatively involved in cell wall biosynthesis using a similar construction under the control of the constitutive promoter glyceraldehyde-3-phosphate dehydrogenase (pgpdA). Silencing of the expression of these two genes was obtained. Further analysis of the transformants showed however that (1) a 100% loss of expression was never achieved for all genes tested (2) the vector used for RNAi is lost or modified over successive transfers resulting in an inhibition of the silencing. These disadvantages of RNAi indicate that classical gene disruption by gene replacement remains the most efficient method for a molecular analysis of gene function in A. fumigatus. PMID- 17273824 TI - Tetrandrine achieved plasma concentrations capable of reversing MDR in vitro and had no apparent effect on doxorubicin pharmacokinetics in mice. AB - PURPOSE: Tetrandrine (Tet), a multidrug resistant (MDR) modulator, was a potential candidate for use in cancer therapy and exhibited potent biological activity in vitro and in vivo when combined with anticancer agents such as doxorubicin, paclitaxel. Our aims were to determine whether serum concentration of Tet, which was capable of blocking P-gp in vitro, could be safely achieved in mice and whether Tet induced pharmacokinetic alterations in serum doxorubicin disposition in mice. METHODS: Tet of 30 mg/kg dose used to reverse MDR was administrated intraperitoneally in mice. Plasma Tet and serum doxorubicin concentration were analyzed by HPLC. CYP 3A4 activity was examined by HPLC with the substrate of nifedipine. RESULTS: More than 1 micromol/L of Tet could at least tenfold reverse MDR in vitro. The plasma peak concentration of Tet was about 2 micromol/L and not less than 1 micromol/L until 18 h following Tet administration (i.p.) at 30 mg/kg. These suggested that the concentrations of Tet that were sufficient to inhibit P-gp might be achieved in mice receiving 30 mg/kg of Tet. Importantly, no significant difference was demonstrated between the doxorubicin pharmacokinetic parameters obtained in mice received doxorubicin only and doxorubicin plus Tet. This implied that Tet of 30 mg/kg did not alter the profiles of pharmacokinetics of doxorubicin including the clearance and AUC of doxorubicin. Furthermore, Tet did not significantly affect on CYP 3A4 activity in human liver microsomes until more than 25 micromol/L. CONCLUSIONS: Tet at the tested dose of combination treatment could achieve plasma concentrations that reversed MDR in experimental models and it had no apparent effect on doxorubicin pharmacokinetics in mice and CYP 3A4 activity in human liver microsomes. PMID- 17273825 TI - Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study. AB - BACKGROUND: Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. METHODS: This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m(2) (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m(2) (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. RESULTS: Forty one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1-6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29-59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3-4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3-4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). CONCLUSION: Gemcitabine 1,000 mg/m(2) on days 1 and 8 in combination with docetaxel 85 mg/m(2) on day 8 given in 3-week cycles is an active and well-tolerated first line chemotherapeutic regimen for advanced NSCLC. PMID- 17273826 TI - Short hairpin RNAs targeting Bcl-xL modulate senescence and apoptosis following SN-38 and irinotecan exposure in a colon cancer model. AB - Bcl-xL is an anti-apoptotic protein over-expressed in colorectal cancers acting on both the intrinsic and extrinsic pathways. We stably expressed four different short hairpin RNA (pSNG-xL1-4) targeting Bcl-xL in HCT 116 cells. HCT 116 pSNG xL#1 produced a modest (30%) decrease in Bcl-xL expression whilst Bcl-2 levels were similar to the parental cell line, HCT 116 pSNG-xL#2 and 3 showed 50% decrease in Bcl-xL and stable Bcl-2. HCT 116 pSNG-xL#3 showed a concomitant decrease (50%) in Bcl-2. A decrease in Bcl-xL sensitised cells to the small molecule inhibitor of Bcl-xL, Antimycin A3 and the DNA topoisomerase I inhibitors, SN-38 and camptothecin, but not to doxorubicin. HCT 116 pSNG-xL#1 produced a moderate increase in both senescence and apoptosis and a limited increase in SN-38 induced cell death while HCT 116 pSNG-xL#2 produced an increase in apoptosis but reduced senescence. Finally, when both Bcl-xL and Bcl-2 were decreased to a similar degree (HCT 116 pSNG-xL#3), senescence was significantly increased but apoptosis was limited. This effect was confirmed in vivo after administration of irinotecan and was associated with greater anti-tumour effect. Optimal growth inhibitory effect was therefore observed when both Bcl-xL and Bcl 2 were decreased to a similar extent. Antimycin A3, in combination with SN-38 recapitulated this phenotype in HCT 116 cells, suggesting a potential role for small molecule inhibitors of Bcl-xL/Bcl-2 in the treatment of colorectal cancer, potentially in combination with irinotecan. PMID- 17273827 TI - Phase II study of biweekly administration of docetaxel and irinotecan in patients with refractory or relapsed advanced non-small cell lung cancer. AB - We examined the safety and efficacy of the combination of docetaxel and irinotecan administered biweekly in patients with refractory or relapsed advanced non-small cell lung cancer (NSCLC). Patients with previously treated NSCLC of stage III or IV were eligible if they had a performance status of 2 or less, were 75 years or younger, and had adequate organ function. From May 2003 through February 2006, 35 patients (27 men and 8 women; median age 64 years; age range 41 75 years) were enrolled. Patients were treated every 4 weeks with docetaxel (33 mg/m(2) on days 2 and 16) plus irinotecan (50 mg/m(2) on days 1 and 15). None of the 35 patients achieved a complete response, but five achieved a partial response, for an overall response rate of 14.3% (95% confidence interval, 4.8 30.3%). The median survival time was 8 months (range 2-29 months). The median time to progression was 3 months (range 1-12 months). Grade 3 to 4 hematologic toxicities included leukopenia in 48.6% of patients, neutropenia in 54.3%, and anemia in 25.7%. No patients had grade 3 to 4 diarrhea or nausea and vomiting. Although one patient had grade 3 drug-induced interstitial pneumonia, all side effects were manageable, and there were no treatment-related deaths. In conclusion, the combination of docetaxel and irinotecan administered biweekly is a safe and effective treatment for refractory or relapsed NSCLC. However, the search for even more active regimens should be continued. PMID- 17273828 TI - Seroprevalence of measles among Norwegian military conscripts in 2004. AB - The study presented here was conducted in order to evaluate the impact of Norway's childhood immunization program against measles, which was implemented in 1969. In the study, the level of measles immunity was measured among 1,405 military conscripts belonging to the first childhood immunization cohorts that were offered two doses of the measles, mumps and rubella vaccine. The overall seroprevalence of measles antibodies in this cohort was 89.3%. Two commercially available antibody assays were used, and the discordance between the two assays was 10.5%. Similar levels of immunity to measles were detected in earlier studies of Norwegian conscripts belonging to different childhood immunization cohorts. PMID- 17273829 TI - Commentary on "Oral purified bacterial extracts in acute respiratory tract infections in childhood: a systematic review". PMID- 17273830 TI - Extensive brown tumors caused by parathyroid adenoma in an adolescent patient. AB - Primary hyperparathyroidism is a rare endocrine disease in children and young adults. The early detection and treatment of primary hyperparathyroidism led to a marked decrease in classical bone and renal manifestations of the disease. Osteitis fibrosa cystica and brown tumors have become extremely rare clinical entities. Moreover, the skeletal involvement in primary hyperparathyroidism secondary to parathyroid adenoma is extremely rare. We report on an adolescent girl with multiple brown tumors and a history of recurrent fractures as the manifestation of primary hyperparathyroidism associated with a parathyroid adenoma. The patient's clinical presentation mimicked parathyroid carcinoma. She had a large tumor associated with marked elevation in the parathyroid hormone and serum calcium levels. Skeletal manifestations were also atypical for benign primary hyperparathyroidism, with widespread brown tumors in the patient. PMID- 17273831 TI - Bullying behaviours and psychosocial health: results from a cross-sectional survey among high school students in Istanbul, Turkey. AB - The aim of this study was to investigate bullying behaviours and their associations with health and health risk behaviours. This study involved completion of the Health Behaviour in School-Aged Children (HBSC) and Youth Self Report (YSR) questionnaires by 3,519 students. Of the students, 59.4% (n=2,091) were neither bullies/nor victims, 22% (n=774) victims, 9.4% (n=331) bully/victims and 9.2% (n=323) bullies. Generally, students involved in bullying behaviours were more likely to have higher YSR scale scores than students who were not involved in bullying behaviours. Bully/victims had higher scores on the YSR subscales than others. Students involved in bullying behaviours were more likely not to use seat belts, to watch TV >or= 4 h/day, to be involved in a physical fight, to skip class and to spend time with friends than students who were not involved in bullying behaviours. Bully/victims and bullies were more likely to smoke cigarettes, to drink alcohol, to be drunk, to play computer games and to be sexually active than others. Bully/victims were more likely to have less educated mothers and to have difficulty in talking to both parents than others. Victims were more likely to have a lower socioeconomic status, to have difficulty in talking to opposite gender friends and to have difficulty in making new friends than others. Bullying behaviour is common and associated with other risk behaviours and psychological health problems in Istanbul high school students. Health professionals should be aware of the influence of bullying on health and particularly on bully/victims' health. There is a strong need for bullying prevention programmes in schools in Turkey. PMID- 17273832 TI - [Prognostic markers for congenital hydronephroses]. AB - Watchful waiting has become the standard therapy in most cases of asymptomatic unilateral congenital hydronephroses with normal renal function. Simple, reliable, and noninvasive prognostic parameters that predict an increased risk of functional deterioration either at the initial evaluation or during follow-up would be most useful. At the moment the diameter of the renal pelvis and especially its increase is the most useful prognostic parameter, while an "obstructed" washout at furosemide isotope renography is of limited prognostic value. Preclinical and preliminary clinical studies indicate that the measurement of molecules in the urine of affected children such as TGF-31 and MCP-1 that are involved in the signal transduction during hydronephrotic atrophy might become well accepted as useful prognostic parameters in the near future. PMID- 17273834 TI - Use of ACE inhibitors is associated with elevated levels of IGFBP-3 among hypertensive older adults: results from the IlSIRENTE study. AB - OBJECTIVE: Several studies in vitro or in rodent models have suggested a potential relationship between angiotensin-converting enzyme (ACE) inhibition and the insulin-like growth factor 1 (IGF-1) axis. However, this relationship has only rarely been investigated in humans. The aim of the present cross-sectional study was to assess the association of ACE inhibitors with free IGF-1 and IGFBP-3 in the blood of older hypertensive adults. METHODS: Data are from the baseline evaluation of the IlSIRENTE study, which enrolled 364 subjects aged 80 or older. For the present study we selected a subpopulation of 264 hypertensive participants without congestive heart failure. Free IGF-1 and IGFBP-3 in the blood were measured by a radioimmunoassay method. Analyses of covariance were performed to evaluate the differences in free IGF-1 and IGFBP-3 levels according to the use of ACE inhibitors. RESULTS: The mean age of participants was 85.7 years (SD: 4.9), 170 (64%) were women and 123 (47%) were using an ACE inhibitor. Following adjustment for potential confounders, the concentration of free IGF-1 was slightly, but not significantly higher among ACE inhibitor users than among non-users (0.74 vs. 0.65 ng/mL; p=0.20). In contrast, ACE inhibitor users had a significantly higher IGFBP-3 serum levels than non-users (4821 vs. 4330 ng/mL; p=0.005). In addition, the concentration of IGFBP-3 was significantly higher among ACE inhibitors users than among non-users of antihypertensive drugs (p=0.02) and users of other antihypertensive drugs (p=0.01). CONCLUSION: Among hypertensive older adults, ACE inhibitors use is associated with higher IGFBP-3 levels. PMID- 17273833 TI - [Spinal anaesthesia in day-case surgery. Optimisation of procedures]. AB - BACKGROUND: Since prilocaine is being increasingly used for day case surgery as a short acting local anaesthetic for spinal anaesthesia and because of its low risk for transient neurological symptoms, we compared it to bupivacaine. PATIENTS AND METHODS: Patients (n=88) who were scheduled for lower limb surgery with spinal anaesthesia randomly received 15 mg hyperbaric bupivacaine 0.5% or 60 mg hyperbaric prilocaine 2% (administered in a sitting position). Onset time, intensity, duration of the sensomotoric block, vital parameters and time of spontaneous miction were recorded and patients were questioned on satisfaction with the anaesthesia procedure and the occurrence of adverse side-effects after 24 h. RESULTS: Bupivacaine caused a significantly higher sensory block than prilocaine (T6 vs. T8). Both groups were similar in reaching an analgesic level of at least T12, block intensity and onset times. Median analgesic levels at T12 were maintained for 60 min with prilocaine versus 120 min with bupivacaine, regression of the motor block was 135 min versus 210 min, sensory block S1 was 240 min versus 360 min, and time for spontaneous miction was 306 min versus 405 min, respectively (differences for all comparisons were statistically significant). CONCLUSION: Under the present study conditions, hyperbaric prilocaine 2% was superior to hyperbaric bupivacaine 0.5% due to a shorter effect profile but otherwise equivalent quality of block. However, puncture in a sitting position and positioning with elevated torso for restriction of the cranial expansion of block spread might cause an enhanced sacral block with delayed recovery of bladder function. PMID- 17273836 TI - The pathogenesis of calyceal diverticular calculi. AB - Controversy exists over whether metabolic factors or urinary stasis predominate in the pathogenesis of calyceal diverticular calculi. We performed a study to better define the effects urinary stasis and metabolic abnormalities have in the pathogenesis of calyceal diverticular stones. Twenty-nine patients who underwent percutaneous treatment of calyceal diverticular calculi were studied. All patients underwent 24 h urine collection to evaluate metabolic risk factors. In three patients, urine was sampled directly from the diverticulum for metabolic studies. The urinary stone risk parameters of the patients with calyceal diverticular stones (Tic SF) were similar to those of a well-characterized cohort of calcium oxalate stone formers (CaOx SF). When compared to a group of normal people, the Tic SF and CaOx SF were significantly more hypercalciuric and their urine was significantly more supersaturated with calcium oxalate. Urine aspirated directly from the diverticulum had the lowest SSCaOx when compared to ipsilateral and contralateral renal pelves. The urinary risk profiles of patients with diverticular calculi are similar to those of CaOx SF, suggesting a metabolic etiology of diverticular stones. However, the SS CaOx of urine aspirated directly from the diverticula is significantly lower than that of the renal pelves; these data support the hypothesis that urinary stasis significantly contributes to the pathogenesis of calyceal diverticular calculi. Taken together, it seems likely that calyceal diverticular calculi arise from a combination of metabolic abnormalities and urinary stasis. PMID- 17273835 TI - Evaluation of probe drugs and pharmacokinetic metrics for CYP2D6 phenotyping. AB - INTRODUCTION: Cytochrome P450 2D6 (CYP2D6) is one of the most important enzymes catalyzing biotransformation of xenobiotics in the human liver. This enzyme's activity shows a high degree of interindividual variability caused in part by its genetic polymorphism, the so-called debrisoquine/sparteine polymorphism. The genetic component influencing CYP2D6 activity can be determined by genotyping. However, genotyping alone is not sufficient to accurately predict an individual's actual CYP2D6 activity, as this is also influenced by other factors. For the determination of the exact actual enzymatic activity ("phenotyping"), adequate probe drugs have to be administered prior to measurements of these compounds and/or their metabolites in body fluids. PROBE DRUGS: Debrisoquine, sparteine, metoprolol or dextromethorphan represent well-established probe drugs while tramadol has been recently investigated for this purpose. The enzymatic activity is reflected by various pharmacokinetic metrics such as the partial clearance of a parent compound to the respective CYP2D6-mediated metabolite or metabolic ratios. Appropriate metrics need to fulfill pre-defined validation criteria. METHODS: In this review, we have compiled a list of such criteria useful to select the best metrics to reflect CYP2D6 activity. A comprehensive Medline search for reports on CYP2D6 phenotyping trials with the above mentioned probe drugs was carried out. CONCLUSION: Application of the validation criteria suggests that dextromethorphan and debrisoquine are the best CYP2D6 phenotyping drugs, with debrisoquine having the problem of very limited availability as a therapeutic drug. However, the assessment of the best dextromethorphan CYP2D6 phenotyping metric/procedure is still ongoing. PMID- 17273837 TI - Loading is more effective than posture in lumbar spinal stenosis: a study with a treadmill equipment. AB - The objective of this study was to assess the correlation between neurogenic intermittent claudication (NIC) in LSS and different positions as well as loading status, using the treadmill device. The study was a prospective clinical trial on lumbar spinal stenosis (LSS) using a treadmill equipment. The study population comprised of 80 LSS patients with a mean age of 61. The equipment included a treadmill, unloading station and loading vests. The patients were instructed to walk in five different positions. The initiation time of symptoms and total walking time were recorded. The examination was stopped after 20 min or at the onset of severe symptoms. In order to obtain pretest demographic data on subjects, visual analog scale, Roland-Morris questionnaire, pain disability index, and Beck depression index were used. The initiation time of symptoms (ITS) and total walking time (TWT) were measured during the test. Unloading provided a longer and loading a shorter ITS and TWT. Decline or incline positions did not affect ITS or TWT. The changes in posture had no correlation with the appearance of symptoms in LSS patients with NIC on a treadmill in this study, rather ITS and TWT were determined by axial loading and unloading. PMID- 17273838 TI - Pullout strength of anterior spinal instrumentation: a product comparison of seven screws in calf vertebral bodies. AB - A lot of new implant devices for spine surgery are coming onto the market, in which vertebral screws play a fundamental role. The new screws developed for surgery of spine deformities have to be compared to established systems. A biomechanical in vitro study was designed to assess the bone-screw interface fixation strength of seven different screws used for correction of scoliosis in spine surgery. The objectives of the current study were twofold: (1) to evaluate the initial strength at the bone-screw interface of newly developed vertebral screws (Universal Spine System II) compared to established systems (product comparison) and (2) to evaluate the influence of screw design, screw diameter, screw length and bone mineral density on pullout strength. Fifty-six calf vertebral bodies were instrumented with seven different screws (USS II anterior 8.0 mm, USS II posterior 6.2 mm, KASS 6.25 mm, USS II anterior 6.2 mm, USS II posterior 5.2 mm, USS 6.0 mm, USS 5.0 mm). Bone mineral density (BMD) was determined by quantitative computed tomography (QCT). Failure in axial pullout was tested using a displacement-controlled universal test machine. USS II anterior 8.0 mm showed higher pullout strength than all other screws. The difference constituted a tendency (P = 0.108) when compared to USS II posterior 6.2 mm (+19%) and was significant in comparison to the other screws (+30 to +55%, P < 0.002). USS II posterior 6.2 mm showed significantly higher pullout strength than USS 5.0 mm (+30%, P = 0.014). The other screws did not differ significantly in pullout strength. Pullout strength correlated significantly with BMD (P = 0.0015) and vertebral body width/screw length (P < 0.001). The newly developed screws for spine surgery (USS II) show higher pullout strength when compared to established systems. Screw design had no significant influence on pullout force in vertebral body screws, but outer diameter of the screw, screw length and BMD are good predictors of pullout resistance. PMID- 17273839 TI - Spontaneous healing of retroperitoneal chylous leakage following anterior lumbar spinal surgery: a case report and literature review. AB - Cisterna chyli is prone to injury in any retroperitoneal surgery. However, retroperitoneal chylous leakage is a rare complication after anterior spinal surgery. To the best of our knowledge, only ten cases have been reported in the English literature. We present a case of a 49-year-old man who had lumbar metastasis and associated radiculopathy. He had transient retroperitoneal chylous leakage after anterior tumor decompression, interbody bony fusion, and instrumental fixation from L2 to L4. The leakage stopped spontaneously after we temporarily clamped the drain tube. Intraperitoneal ascites accumulation developed thereafter due to nutritional loss and impaired hepatic reserves. We gathered ten reported cases of chylous leak after anterior thoracolumbar or lumbar spinal surgery, and categorized all these cases into two groups, depending on the integrity of diaphragm. Six patients received anterior spinal surgery without diaphragm splitting. Postoperative chylous leak stopped after conservative treatment. Another five cases received diaphragm splitting in the interim of anterior spinal surgery. Chylous leakage stopped spontaneously in four patients. The remaining one had a chylothorax secondary to postop chyloretroperitoneum. It was resolved only after surgical intervention. In view of these cases, all the chylous leakage could be spontaneously closed without complications, except for one who had a secondary chylothorax and required thoracic duct ligation and chemopleurodesis. We conclude that intraoperative diaphragm splitting or incision does not increase the risk of secondary chylothorax if it was closed tightly at the end of the surgery and the chest tube drainage properly done. PMID- 17273840 TI - Quality of life and functional status in patients with cancer of the oral cavity and oropharynx: pretreatment values of a prospective study. AB - We assessed the pretreatment health-related quality of life (HRQOL) and functional status of patients with advanced oral and oropharyngeal cancer. Eighty patients were investigated. HRQOL was assessed by EORTC QLQ-C30/QLQ-H&N35 questionnaires. Functional status assessment comprised speech and oral function tests. The results revealed a wide range of HRQOL and functional deficits before treatment. HRQOL appeared to be related to some extent to tumor site (patients with oral tumors reported more pain compared to patients with oropharyngeal tumors) and tumor classification (patients with T3-T4 tumors reported more trouble opening the mouth and felt more ill compared to patients with T2 tumors). Comorbidity appeared to have a major impact. Patients with comorbidity had significantly worse scores on several scales/items on both the EORTC questionnaires. Functional deficits were related to tumor site, classification and comorbidity. Patients with oral cavity tumors (versus oropharyngeal tumors), patients with T3-T4 tumors (versus T2 tumors), and patients with comorbidity (versus without comorbidity) scored significantly worse on several speech and oral function tests. Impaired speech and oral function appeared to be clearly related to global quality of life (QLQ-C30) and self-reported speech (QLQ-H&N35). Many patients with advanced oral and oropharyngeal cancer have compromised HRQOL and functional status before the start of treatment. In addition to tumor site and tumor classification, comorbidity appears to have a major impact on HRQOL and functional status. Knowledge of pretreatment HRQOL and functional status levels is useful for better understanding the impact of treatment on these outcomes over time. PMID- 17273841 TI - The first avian Ig-like Fc receptor family member combines features of mammalian FcR and FCRL. AB - Homologues of almost all mammalian Ig-like immunoregulatory receptor families have been found in the chicken, except the Fc receptor (FcR) family. In addition to classical FcRs that specifically bind antibodies and mediate their effector functions, this family includes "Fc receptor-like" (FCRL) proteins for which ligands have yet to be identified. We have cloned and expressed a full-length chicken monocyte transcript that encodes an avian homologue of the mammalian FcR family. We have termed it chFcR/L as it possesses characteristics of both mammalian FcR and FCRL, but is phylogenetically distinct from either. chFcR/L is a transmembrane protein with four extracellular Ig-like domains and a short cytoplasmic tail. It can be expressed on the cell surface only in the presence of an accessory molecule, chFcRgamma, through which it acquires signalling potential. PMID- 17273842 TI - [Surgical technique of en bloc spondylectomy for solitary metastases of the thoracolumbar spine]. PMID- 17273843 TI - A novel locus for autosomal recessive spastic ataxia on chromosome 17p. AB - Autosomal recessive spastic ataxias are a heterogeneous group of neurodegenerative diseases usually characterized by the early onset of cerebellar and pyramidal signs. With the collaboration of the clinical European and Mediterranean SPATAX network, we identified 15 families with 34 affected members presenting with ataxia and pyramidal signs or spasticity that were not linked to the ARSACS locus on chromosome 13. In an informative consanguineous Moroccan family, we mapped a novel locus, SAX2, to chromosome 17p13. The minimal linked interval lies in a region of 6.1 cM flanked by markers D17S1845/1583 and D17S1854 (Z(max) = 3.21). Three of the remaining 14 families were also possibly linked to SAX2. The overall clinical picture in nine patients was cerebellar ataxia with pyramidal signs and/or spasticity. Onset occurred before the age of 15 years in two families and in adulthood in the other two. Interestingly, in the largest SAX2 family, the presenting clinical sign was dysarthria, which is not common in other forms of inherited ataxias or spastic ataxias, whereas gait difficulties appeared later. Most cases also showed fasciculations suggesting that both lower and upper motor neurons are involved in the disease process. No mutations were found in the coding exons of KIF1C, ARRB2 and ANKFY1, three genes in the candidate region. PMID- 17273844 TI - Quantitative effects of common genetic variations in the 3'UTR of the human LDL receptor gene and their associations with plasma lipid levels in the Atherosclerosis Risk in Communities study. AB - The low-density lipoprotein receptor (LDLR) plays a pivotal role in cholesterol homeostasis. However, the role of genetic variations in the 3'UTR of the LDLR in relation to plasma cholesterol has been largely understudied. Six SNPs, G44243A, G44332A, C44506G, G44695A, C44857T and A44964G, within the 5' region of the 3'UTR fall into three common haplotypes, GGCGCA, AGCACG, and GGCGTA, occurring at frequencies of 0.45, 0.31 and 0.17, respectively, in Caucasians (n = 29) and 0.13, 0.13 and 0.38, respectively, in African Americans (n = 32), with three other haplotypes occurring at lesser frequencies. In a tissue culture based system, expression of a reporter gene carrying a 3'UTR that includes the 1 kb nucleotide sequences corresponding to the AGCACG or GGCGTA was 70 or 63%, respectively, of the same sequence with GGCGCA. Genotyping of two "haplotype tagging" SNPs, C44857T and A44964G, in the Atherosclerosis Risk in Communities (ARIC) study population showed that in Caucasians, but not in African Americans, the inferred TA haplotype had a significant LDL-cholesterol lowering effect. The adjusted LDL-cholesterol levels in the TA/TA diplotypes were lower by 6.10 mg/dl in men (P < 0.001) and by 4.63 mg/dl in women (P < 0.01) than in individuals with other diplotypes. Caucasian men homozygous for CA, in contrast, showed significantly higher LDL-cholesterol (P < 0.04), lower HDL-cholesterol (P < 0.02) and higher LDL/HDL ratios (P < 0.001). Thus our data shows that 3'UTR sequences that cause higher reporter gene expression in vitro are associated in Caucasians with plasma lipid profiles indicative of higher cardiovascular risk, suggesting that further studies of quantitative variants in the LDLR gene will be valuable. PMID- 17273846 TI - The distribution of genetic diversity in a Brassica oleracea gene bank collection related to the effects on diversity of regeneration, as measured with AFLPs. AB - The ex situ conservation of plant genetic resources in gene banks involves the selection of accessions to be conserved and the maintenance of these accessions for current and future users. Decisions concerning both these issues require knowledge about the distribution of genetic diversity within and between accessions sampled from the gene pool, but also about the changes in variation of these samples as a result of regenerations. These issues were studied in an existing gene bank collection of a cross-pollinating crop using a selection of groups of very similar Dutch white cabbage accessions, and additional groups of reference material representing the Dutch, and the global white cabbage gene pool. Six accessions were sampled both before and after a standard regeneration. 30 plants of each of 50 accessions plus 6 regeneration populations included in the study were characterised with AFLPs, using scores for 103 polymorphic bands. It was shown that the genetic changes as a result of standard gene bank regenerations, as measured by AFLPs, are of a comparable magnitude as the differences between some of the more similar accessions. The observed changes are mainly due to highly significant changes in allele frequencies for a few fragments, whereas for the majority of fragments the alleles occur in similar frequencies before and after regeneration. It is argued that, given the changes of accessions over generations, accessions that display similar levels of differentiation may be combined safely. PMID- 17273845 TI - The construction of a Solanum habrochaites LYC4 introgression line population and the identification of QTLs for resistance to Botrytis cinerea. AB - Tomato (Solanum lycopersicum) is susceptible to grey mold (Botrytis cinerea). Partial resistance to this fungus has been identified in accessions of wild relatives of tomato such as Solanum habrochaites LYC4. In a previous F(2) mapping study, three QTLs conferring resistance to B. cinerea (Rbcq1, Rbcq2 and Rbcq4a) were identified. As it was probable that this study had not identified all QTLs involved in resistance we developed an introgression line (IL) population (n = 30), each containing a S. habrochaites introgression in the S. lycopersicum cv. Moneymaker genetic background. On average each IL contained 5.2% of the S. habrochaites genome and together the lines provide an estimated coverage of 95%. The level of susceptibility to B. cinerea for each of the ILs was assessed in a greenhouse trial and compared to the susceptible parent S. lycopersicum cv. Moneymaker. The effect of the three previously identified loci could be confirmed and seven additional loci were detected. Some ILs contains multiple QTLs and the increased resistance to B. cinerea in these ILs is in line with a completely additive model. We conclude that this set of QTLs offers good perspectives for breeding of B. cinerea resistant cultivars and that screening an IL population is more sensitive for detection of QTLs conferring resistance to B. cinerea than the analysis in an F(2) population. PMID- 17273848 TI - Spatial orientation in the bushcricket Leptophyes punctatissima (Phaneropterinae; Orthoptera): II. Phonotaxis to elevated sound sources on a walking compensator. AB - The ability of the bushcricket Leptophyes punctatissima to orient to elevated sound sources was investigated. Males were placed on a walking compensator and oriented in response to a synthetic female reply, which was broadcast via one of five loudspeakers placed at elevations of 0 degrees , 30 degrees , 60 degrees , 75 degrees and 90 degrees . Forward and backward movements were compensated, so that males remained at the same distance and elevation to the sound source. With increasing loudspeaker elevation, the males meandered more, and the ratio of the ideal path length to the actual path length decreased. The same was true for the correlation between stimulus angle and turn angle, and there were more turns to the wrong side with increasing loudspeaker elevation. Most males performed phonotaxis with a high acuity up to an elevation of 60 degrees . Individuals varied strongly in their performance especially at a source elevation of 75 degrees , where some were still very accurate in their approach, whereas the acuity of others decreased rapidly. We also describe a behaviour where males tilt their body axis to more anterior and sideward positions, both during walking and while calling on the spot. This behaviour is interpreted as a kind of directional scanning in order to actively induce changes in binaural cues. PMID- 17273847 TI - Evidence of a possible impact of the menstrual cycle on the reproducibility of scotopic ERGs in women. AB - The purpose of this study was to investigate the impact of gender and menstrual cycle on the electroretinogram (ERG). Photopic and scotopic ERGs were obtained in 14 females during the luteal and follicular phases of their menstrual cycle and compared to those obtained on two separate (7 days or 14 days apart) sessions from seven age-matched control male subjects. Our results confirm that the amplitude of the photopic ERGs of females is significantly (P < 0.05) larger than males, and this, irrespective of the cycle phase. In comparison, scotopic ERGs revealed significant male-female differences only during the follicular phase. While in males, no significant (P > 0.05) intersession (7 day or 14 day intervals) variability could be demonstrated, significant (P < 0.001) intersession (luteal-follicular) variability was observed in the scotopic ERGs of our female participants, with 8 of the 14 women, demonstrating a marked increase of 20.17 +/- 4.8% in the follicular ERG compared to the luteal. Our data suggests there should be separate normal ERG values for men and women and that the phase of the menstrual cycle should be taken into consideration when interpreting the ERG results from women. PMID- 17273851 TI - Comment on "Pulse oximetry" by Jubran. PMID- 17273849 TI - The mapping of visual space by dragonfly lateral ocelli. AB - We study the extent to which the lateral ocelli of dragonflies are able to resolve and map spatial information, following the recent finding that the median ocellus is adapted for spatial resolution around the horizon. Physiological optics are investigated by the hanging-drop technique and related to morphology as determined by sectioning and three-dimensional reconstruction. L-neuron morphology and physiology are investigated by intracellular electrophysiology, white noise analysis and iontophoretic dye injection. The lateral ocellar lens consists of a strongly curved outer surface, and two distinct inner surfaces that separate the retina into dorsal and ventral components. The focal plane lies within the dorsal retina but proximal to the ventral retina. Three identified L neurons innervate the dorsal retina and extend the one-dimensional mapping arrangement of median ocellar L-neurons, with fields of view that are directed at the horizon. One further L-neuron innervates the ventral retina and is adapted for wide-field intensity summation. In both median and lateral ocelli, a distinct subclass of descending L-neuron carries multi-sensory information via graded and regenerative potentials. Dragonfly ocelli are adapted for high sensitivity as well as a modicum of resolution, especially in elevation, suggesting a role for attitude stabilisation by localization of the horizon. PMID- 17273852 TI - Risk adjustment policy options for casemix funding: international lessons in financing reform. AB - This paper explores modified hospital casemix payment formulae that would refine the diagnosis-related group (DRG) system in Victoria, Australia, which already makes adjustments for teaching, severity and demographics. We estimate alternative casemix funding methods using multiple regressions for individual hospital episodes from 2001 to 2003 on 70 high-deficit DRGs, focussing on teaching hospitals where the largest deficits have occurred. Our casemix variables are diagnosis- and procedure-based severity markers, counts of diagnoses and procedures, disease types, complexity, day outliers, emergency admission and "transfers in." The results are presented for four policy options that vary according to whether all of the dollars or only some are reallocated, whether all or some hospitals are used and whether the alternatives augment or replace existing payments. While our approach identifies variables that help explain patient cost variations, hospital-level simulations suggest that the approaches explored would only reduce teaching hospital underpayment by about 10%. The implications of various policy options are discussed. PMID- 17273853 TI - Kinetic models for peptide-induced leakage from vesicles and cells. AB - In this article analytical expressions for peptide-induced membrane leakage are presented. Two different models for time-dependent leakage have been developed. In the first, the leakage is assumed to be coupled by pores formed by the peptides. In the second model the peptide is assumed to induce a stress/perturbation in the membrane, and in order to reduce the stress, rearrangements in the membrane are induced. The leakage is coupled to these rearrangements, and when equilibrium is achieved no more leakage occurs. From the kinetic models simple fitting routines have been developed involving only two fitting parameters, and these have been used to fit experimental data for two prion protein-derived peptides as well as the honey bee toxin melittin in both vesicles and erythrocytes with good results. The fitted parameters provide both a quantitative and a qualitative basis for interpreting the experimental results. In addition a model for the peptide concentration-dependent leakage is presented, which was used to fit experimental data for leakage induced by the prion protein derived peptides. The models presented in this article are compared with other models for peptide-induced membrane leakage. PMID- 17273854 TI - Field study results on the probability and risk of a horizontal gene transfer from transgenic herbicide-resistant oilseed rape pollen to gut bacteria of bees. AB - Bees are specifically subjected to intimate contacts with transgenic plants due to their feeding activities on pollen. In this study, the probability and ecological risk of a gene transfer from pollen to gut bacteria of bees was investigated with larvae of Apis mellifera (honeybee), Bombus terrestris (bumblebee), and Osmia bicornis (red mason bee), all collected at a flowering transgenic oilseed rape field. The plants were genetically engineered with the pat-gene, conferring resistance against glufosinate (syn. phosphinothricin), a glutamine-synthetase inhibitor in plants and microorganisms. Ninety-six bacterial strains were isolated and characterized by 16S rRNA gene sequencing, revealing that Firmicutes represented 58% of the isolates, Actinobacteria 31%, and Proteobacteria 11%, respectively. Of all isolates, 40% were resistant to 1 mM glufosinate, and 11% even to 10 mM. Resistant phenotypes were found in all phylogenetic groups. None of the resistant phenotypes carried the recombinant pat gene in its genome. The threshold of detecting gene transfer in this field study was relatively insensitive due to the high background of natural glufosinate resistance. However, the broad occurrence of glufosinate-resistant bacteria from different phylogenetic groups suggests that rare events of horizontal gene transfer will not add significantly to natural bacterial glufosinate resistance. PMID- 17273855 TI - Global gene expression analysis of glucose overflow metabolism in Escherichia coli and reduction of aerobic acetate formation. AB - During aerobic growth on glucose, Escherichia coli produces acetate in the so called overflow metabolism. DNA microarray analysis was used to determine the global gene expression patterns of chemostat cultivations of E. coli MG1655 that were characterized by different acetate formation rates during aerobic growth on glucose. A correlation analysis identified that expression of ten genes (sdhCDAB, sucB, sucC, acnB, lpdA, fumC and mdh) encoding the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase, aconitase, fumarase and malate dehydrogenase, respectively, and of the acs-yjcH actP operon for acetate utilization correlated negatively with acetate formation. Relieving transcriptional control of the sdhCDAB-b0725-sucABCD operon by chromosomal promoter exchange mutagenesis yielded a strain with increased specific activities of the TCA cycle enzymes succinate dehydrogenase, alpha ketoglutarate dehydrogenase and succinyl-CoA synthetase, which are encoded by this operon. The resulting strain produced less acetate and directed more carbon towards carbon dioxide formation than the parent strain MG1655 while maintaining high growth and glucose consumption rates. PMID- 17273856 TI - Arbuscular mycorrhizal fungi can induce the production of phytochemicals in sweet basil irrespective of phosphorus nutrition. AB - The potential of three arbuscular mycorrhizal fungi (AMF) to enhance the production of antioxidants (rosmarinic and caffeic acids, RA and CA) was investigated in sweet basil (Ocimum basilicum). After adjusting phosphorus (P) nutrition so that P concentrations and yield were matched in AM and non mycorrhizal (NM) plants we demonstrated that Glomus caledonium increased RA and CA production in the shoots. Glomus mosseae also increased shoot CA concentration in basil under similar conditions. Although higher P amendments to NM plants increased RA and CA concentrations, there was higher production of RA and CA in the shoots of AM plants, which was not solely due to better P nutrition. Therefore, AMF potentially represent an alternative way of promoting growth of this important medicinal herb, as natural ways of growing such crops are currently highly sought after in the herbal industry. PMID- 17273857 TI - The recurrent aphthous stomatitis frequency in the smoking cessation people. AB - This study was aimed to evaluate the frequency of recurrent aphthous stomatitis (RAS) within the 6-week period after quitting smoking. The study group consisted of 90 subjects. Oral, medical findings and tobacco habits were recorded for all subjects. Nicotine replacement therapy (NRT) and behavioral treatment were applied to some of the subjects by a family physician. All subjects were evaluated for their RAS and periodontal measurements on baseline, 1, 3, 6 weeks by a periodontist. While the subjects were in this smoking cessation programme, 64 of the 90 smokers successfully quit smoking within the 6 weeks and 26 smokers dropped out during the third week of the study. Point prevalence of RAS among the subjects on the first day of the quitting period and at the end of the first, third and sixth week after smoking cessation was 3.3% (3/90), 18.9% (17/90), 21.1% (19/90) and 17.1 (11/64), respectively. In the following weeks, aphthous ulcer point prevalence was significantly higher than the quitting level (p < 0.05). As the time after quitting increased, the incidence of aphthous ulcer decreased. Of 64 patients, 35 (54.6%) completed the 6 weeks using NRT and 29 (45.4%) of them did not use any medication. The aphthous ulcer frequency observed in the patients taking NRT [11.4% (4/35)] was lower when compared with the subjects taking no NRT [24.1% (7/29)] (p > 0.05). The results of this study confirm that RAS is a complication of quitting smoking. Further studies are needed to identify the effects of NRT on RAS. PMID- 17273858 TI - Dental erosion in chronic renal failure. AB - Dental erosion is a common oral finding in chronic renal failure and may develop due to extrinsic and/or intrinsic causes. The aim of this study was to compare the salivary calcium and phosphorus levels, salivary flow rate, salivary buffer capacity, salivary pH, serum calcium and phosphorus levels and parathyroid hormone levels in chronic renal failure patients with and without dental erosion. Twenty-four men and 19 women who had had chronic renal failure for at least 2 years were studied. Twenty-two subjects displayed erosion-like patterns on their teeth and the other 21 patients showed no signs of erosion. Two closely age- and sex-matched control groups (control groups 1 and 2) were enrolled in this study because of the age disparity between the erosion and non-erosion groups. The data were analyzed by Mann-Whitney U test, Student t test, Pearson's and Spearman's correlation tests. None of the comparisons were statistically different between the erosion and non-erosion groups. There were statistically significant differences in salivary calcium (P < 0.01) and phosphorus (P < 0.01) levels, serum phosphorus level (P < 0.01) and serum PTH level (P < 0.01) for the erosion group and control group 1 and also for the non-erosion group and control group 2. There was also a significant difference in salivary flow rate (P < 0.05) for the erosion group and control group 1. There was a positive significant correlation between saliva buffer capacity and salivary phosphorus level (r = 0.454, P < 0.05) in the erosion group. PMID- 17273859 TI - Determination of reducing ends with flow injection analysis with amperometric detection: application to enzyme-hydrolysed methyl cellulose. AB - A novel method for detection of reducing ends of sugars is proposed, based on the use of [Formula: see text] as the oxidant in combination with amperometric detection and flow injection analysis (FIA). The method is very sensitive, giving values of <10 muM for the limit of detection for a series of mono- and oligosaccharides. Samples can be analysed every 30 s, and injection can be made fully automated, making it possible to perform on-line analysis of polysaccharide samples subjected to hydrolysis. Three methylcelluloses (MC) of different qualities were hydrolysed with three different glucanases, and the concentrations of reducing ends prior to, during and after hydrolysis were determined. Differences were observed between the results obtained using different combinations of enzymes and MCs, which revealed different selectivities of the various enzymes for the different substrates. One MC was also hydrolysed and analysed in real-time for three hours. The method proposed is superior to many of the standard methods used today, which require manual labour and have a lower sensitivity. PMID- 17273860 TI - Acute tubulointerstitial nephritis following ingestion of Chlorella tablets. AB - Here, we report on a boy with acute tubulointerstitial nephritis (ATIN), who developed it following ingestion of Chlorella tablets as a food supplement. He was incidentally detected to have glucosuria, proteinuria, and leukocyturia during school mass screening. He had had a history of ingestion of Chlorella tablets for 3 months. Laboratory studies showed anemia, increased levels of creatinine, decreased glomerular filtration rate (GFR), hypokalemia, hypo uricemia, hypophosphatemia, hypergammaglobulinemia, proteinuria, leukocyturia, and glucosuria. ATIN was diagnosed by renal biopsy. The patient's renal function improved after initiation of corticosteroid therapy and discontinuation of Chlorella for 6 months. Chlorella may be a causative allergen inducing tubulointerstitial injury in kidney. PMID- 17273861 TI - Predictive value of clinical and laboratory variables for vesicoureteral reflux in children. AB - We aimed to determine the predictability of clinical and laboratory variables for vesicoureteral reflux (VUR) in children with urinary tract infection (UTI). Data of children with febrile UTI who underwent voiding cystoureterography between 2002 and 2005 were evaluated retrospectively for clinical (age, gender, fever > or = 38.5 degrees C, recurrent UTI), laboratory [leukocytosis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), pyuria, serum creatinine (S(Cr))] and imaging (renal ultrasonography) variables. Children with VUR (group 1) vs. no VUR (group 2) and children with high-grade (III-V) VUR (group 3) vs. no or low-grade (I-II) VUR (group 4) were compared. Among 88 patients (24 male), 38 had VUR and 21 high-grade VUR. Fever > or = 38.5 degrees C was associated with VUR [odds ratio (OR): 7.5]. CRP level of 50 mg/l was the best cut-off level for predicting high-grade VUR (OR 15.5; discriminative ability 0.89 +/- 0.05). Performing voiding cystourethrography based on this CRP level would result in failure to notice 9% of patients with high-grade VUR, whereas 69% of children with no/low-grade VUR would be spared from this invasive test. In conclusion, fever > or = 38 degrees C and CRP > 50 mg/l seem to be potentially useful clinical predictors of VUR and high-grade VUR, respectively, in pediatric patients with UTI. Further validation of these findings could limit unnecessary voiding cystourethrography. PMID- 17273862 TI - Mesna or cysteine prevents chloroacetaldehyde-induced cell death of human proximal tubule cells. AB - Chloroacetaldehyde (CAA) is formed in the body from the chemotherapeutically used drug ifosfamide (IFO). CAA leads to cell death in proximal tubule cells mainly through the mechanism of necrosis rather than apoptosis. During chemotherapy, 2 mercaptosulfonic acid (mesna) is used with IFO to protect the urothel from cell damage. Little is known of the effect of mesna on renal proximal tubule cells, the primary site of damage after IFO treatment. Mesna contains a sulfhydryl (SH) group. To clarify whether SH-group-containing molecules can prevent CAA-induced cell death, we studied the effect of mesna and cysteine on necrosis, apoptosis, and protein content in a human proximal tubule-derived cell line (IHKE cells) treated with CAA. Both substances prevented CAA-induced necrotic cell death and protein loss and restored CAA-inhibited caspase-3 activity. CAA also prevented cisplatin-induced apoptosis. This inhibition was reversible in the presence of glutathione (GSH). We conclude that SH-containing molecules can protect proximal tubule cells from cell death because they interact with CAA before CAA can disturb other important cellular SH groups. A sufficient supply of intra- and extracellular SH groups during IFO chemotherapy may therefore have the ability to protect renal tubule cells from cell death. PMID- 17273863 TI - Downregulation of neuronal sodium channel subunits Nav1.1 and Nav1.6 in the sinoatrial node from volume-overloaded heart failure rat. AB - Sodium current I(Na) plays an important role in the pacemaker activity of the sinoatrial node (SAN). However, expression profiles of corresponding sodium channel subunits in normal SAN remain unclear. And little is known about expression alteration of sodium channel in SAN under heart failure (HF) condition. We assessed SAN function and expression of Nav1.1, Nav1.2, Nav1.3, Nav1.5, Nav1.6, and Nav1.7 in sham-operated rats and rats subjected to abdominal arteriovenous shunt (volume overload)-induced HF. Immunohistochemistry, Western blot, and quantitative real-time reverse transcriptase PCR analysis were used to quantify sodium channel subunit protein and mRNA expression in the SAN. Intrinsic heart rate declined and sinus node recovery time was prolonged in HF rats, indicating suppressed SAN pacemaker function. In rat SAN, Nav1.1 and Nav1.6 were the primary subunits, Nav1.5 and Nav1.7 were weakly expressed, and Nav1.2 and Nav1.3 were not found to be present. HF significantly decreased SAN sodium channel expression at both the protein and mRNA levels (Nav1.1 by 61 and 71%, Nav1.6 by 49 and 46%, respectively). In conclusion, Nav1.1 and Nav1.6 are the dominant subunits in rat SAN, and downregulation of Nav1.1 and Nav1.6 expression contributes to HF-induced SAN dysfunction. These findings provide additional information about molecular basis of disease-related impairment of SAN function. PMID- 17273864 TI - Recycling of aromatic amino acids via TAT1 allows efflux of neutral amino acids via LAT2-4F2hc exchanger. AB - The rate of amino acid efflux from individual cells needs to be adapted to cellular demands and plays a central role for the control of extracellular amino acid homeostasis. A particular example of such an outward amino acid transport is the basolateral efflux from transporting epithelial cells located in the small intestine and kidney proximal tubule. Because LAT2-4F2hc (Slc7a8-Slc3a2), the best known basolateral neutral amino acid transporter of these epithelial cells, functions as an obligatory exchanger, we tested whether TAT1 (Slc16a10), the aromatic amino-acid facilitated diffusion transporter, might allow amino acid efflux via this exchanger by recycling its influx substrates. In this study, we show by immunofluorescence that TAT1 and LAT2 indeed colocalize in the early kidney proximal tubule. Using the Xenopus laevis oocytes expression system, we show that L-glutamine is released from oocytes into an amino-acid-free medium only when both transporters are coexpressed. High-performance liquid chromatography analysis reveals that several other neutral amino acids are released as well. The transport function of both TAT1 and LAT2-4F2hc is necessary for this efflux, as coexpression of functionally inactive but surface-expressed mutants is ineffective. Based on negative results of coimmunoprecipitation and crosslinking experiments, the physical interaction of these transporters does not appear to be required. Furthermore, replacement of TAT1 or LAT2-4F2hc by the facilitated diffusion transporter LAT4 or the obligatory exchanger LAT1, respectively, supports similar functional cooperation. Taken together, the results suggest that the aromatic amino acid diffusion pathway TAT1 can control neutral amino acid efflux via neighboring exchanger LAT2-4F2hc, by recycling its aromatic influx substrates. PMID- 17273867 TI - Independently silencing two JAR family members impairs levels of trypsin proteinase inhibitors but not nicotine. AB - Jasmonic acid (JA)-amino acid conjugates are important JA metabolites that activate JA responses. However, our understanding of their involvement in herbivore defenses is limited. We identified a new Arabidopsis jasmonate resistant 1 (JAR1) homologue in Nicotiana attenuata (N. attenuata) and named it jasmonate resistant 6 (JAR6). JAR6 clustered closely with Arabidopsis JAR1 and the recently reported jasmonate resistant 4 (JAR4), another JAR1 homologue in N. attenuata, in a phylogenic analysis. The strong elicitation of JAR6 transcripts by wounding and treatment with Manduca sexta (M. sexta) oral secretions (OS), which mimics herbivore attack, suggests it plays a role in herbivore defense. Independently silencing JAR4 or JAR6 by transforming N. attenuata with inverted repeat JAR4 or JAR6 constructs significantly reduced levels of not only JA-Ile plus JA-Leu but also JA-Val in OS-elicited leaves, suggesting JAR4 and JAR6 are functionally redundant and their amino acid substrates are not highly specific to individual amino acids. A new JA conjugate, JA-Gln, whose levels are much higher than those of the other JA conjugates in WT plants, was not affected in JAR4- or JAR6-silenced lines, implying that another JA-conjugating enzyme exists in N. attenuata. Neither JA-ACC, the second most abundant JA conjugate in Arabidopsis seedlings, nor JA-Met or JA-Trp, was detectable in N. attenuata. Levels of trypsin proteinase inhibitors (TPIs) in JAR4- and JAR6-silenced plants were significantly reduced, but nicotine levels were normal. We conclude that both JAR4 and JAR6 conjugate JA to Ile, Val, and Leu, and that both positively regulate TPI activity. PMID- 17273866 TI - Calcineurin A and CaMKIV transactivate PGC-1alpha promoter, but differentially regulate cytochrome c promoter in rat skeletal muscle. AB - In skeletal muscle, slow-twitch fibers are highly dependent on mitochondrial oxidative metabolism suggesting the existence of common regulatory pathways in the control of slow muscle-specific protein expression and mitochondrial biogenesis. In this study, we determined whether peroxisome proliferator activated receptor gamma co-activator-1alpha (PGC-1alpha) could transactivate promoters of nuclear-encoded mitochondrial protein (cytochrome c) and muscle specific proteins (fast troponin I, MyoD). We also investigated if calcineurin A (CnA) and calcium/calmodulin kinase IV (CaMKIV) were involved in the regulation of PGC-1alpha and cytochrome c promoter. For this purpose, we took advantage of the gene electrotransfer technique, which allows acute expression of a gene of interest. Electrotransfer of a PGC-1alpha expression vector into rat Tibialis anterior muscle induced a strong transactivation of cytochrome c promoter (P < 0.001) independent of nuclear respiratory factor 1. PGC-1alpha gene electrotransfer did not transactivate fast troponin I promoter, whereas it did transactivate MyoD promoter (P < 0.05). Finally, whereas electrotransfers of CnA or CaMKIV expression vectors transactivated PGC-1alpha promoter (P < 0.001), gene electrotransfer of CaMKIV was only able to transactivate cytochrome c promoter. Taken together, these data suggest that CnA triggers PGC-1alpha promoter transactivation to drive the expression of non-mitochondrial proteins. PMID- 17273865 TI - Membrane currents and cytoplasmic sodium transients generated by glutamate transport in Bergmann glial cells. AB - Effects of glutamate and kainate (KA) on Bergmann glial cells were investigated in mouse cerebellar slices using the whole-cell configuration of the patch-clamp technique combined with SBFI-based Na(+) microfluorimetry. L-glutamate (1 mM) and KA (100 microM) induced inward currents in Bergmann glial cells voltage-clamped at -70 mV. These currents were accompanied by an increase in intracellular Na+ concentration ([Na+](i)) from the average resting level of 5.2 +/- 0.5 mM to 26 +/- 5 mM and 33 +/- 7 mM, respectively. KA-evoked signals (1) were completely blocked in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/KA ionotropic glutamate receptors; (2) reversed at 0 mV, and (3) disappeared in Na+ -free, N-methyl-D-glucamine (NMDG+)-containing solution, but remained almost unchanged in Na+ -free, Li+ -containing solution. Conversely, L glutamate-induced signals (1) were marginally CNQX sensitive (approximately 10% inhibition), (2) did not reverse at a holding potential of +20 mV, (3) were markedly suppressed by Na+ substitution with both NMDG+ and Li+, and (4) were inhibited by D,L-threo-beta-benzyloxyaspartate. Further, D-glutamate, L -, and D aspartate were also able to induce Na+ -dependent inward current. Stimulation of parallel fibres triggered inward currents and [Na+](i) transients that were insensitive to CNQX and MK-801; hence, we suggested that synaptically released glutamate activates glutamate/Na+ transporter in Bergmann glial cells, which produces a substantial increase in intracellular Na+ concentration. PMID- 17273868 TI - Genome-wide identification and characterization of putative cytochrome P450 genes in the model legume Medicago truncatula. AB - In plants, cytochrome P450 is a group of monooxygenases existing as a gene superfamily and plays important roles in metabolizing physiologically important compounds. However, to date only a limited number of P450s have been identified and characterized in legumes. In this study, data mining methods were used, and 151 putative P450 genes in the model legume Medicago truncatula were identified, including 135 novel sequences. These genes were classified into 9 clans and 44 families by sequence similarity, and among those 4 new clans and 21 new families not reported previously in legumes. By comparison of these genes with P450 genes in Arabidopsis and rice, it was found that most of the known P450 families in dicot species exist in M. truncatula. The representative protein sequences of putative P450s were aligned, and the secondary elements were assigned based on the known structure P450BM3. Putative substrate recognition sites (SRSs) and substrate binding sites were also identified in these sequences. In addition, the ESTs-derived expression profiles (digital Northern) of the putative P450 genes were analyzed, which was confirmed by semi-quantitative RT-PCR analyses of several selected P450 genes. These results will provide a base for catalogue information on P450 genes in M. truncatula and for further functional analysis of P450 superfamily genes in legumes. PMID- 17273869 TI - Adoptive therapy of head and neck squamous cell carcinoma with antibody coated immune cells: a pilot clinical trial. AB - BACKGROUND: Catumaxomab is an antibody that binds with one arm epithelial cell adhesion molecule (EpCAM) positive tumors and with the other arm CD3+ T cells. Intravenous application of therapeutic antibodies may result in intravascular cytokine release. AIM: In this pilot trial we assessed whether cytokine release can be controlled by ex vivo cell opsonization and cytokine wash-out before administration of catumaxomab, preserving its anti-cancer activity. In addition, preliminary data on safety of and clinical response to catumaxomab coated autologous immune cells were acquired. METHODS: Peripheral blood mononuclear cells (PBMNC) of four patients with recurrent head and neck carcinoma were collected by leukapheresis, incubated ex vivo with catumaxomab for 24 h and cleared from released cytokines. Each patient received an escalated number of antibody-coated PBMNC equivalent to 1 x 10(4), 1 x 10(5), 1 x 10(6) and 1 x 10(7) CD3(+) cells/kgBW intravenously at bi-weekly intervals. RESULTS: After opsonization, PBMNC released substantial amounts of interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) in vitro, which were removed before administration. Catumaxomab up-regulated CD25, CD69, and CD83 on PBMNC, and catumaxomab loaded PBMNC released IFNgamma and granzyme B when coincubated with EpCAM(+) BHY cells, suggesting cell activation and target directed biological activity. During the study period, one patient died of aspiration pneumonia and one patient needed a tracheotomy. Treatment related adverse events (AE) occurred at the highest cell dose in two patients, whereas 1 x 10(6) loaded CD3(+) cells/kgBW were well tolerated by all patients. One patient showed stable disease for 6 months and one patient is in complete remission for 27 months. CONCLUSION: Ex vivo opsonization of PBMNC with catumaxomab provided biologically active, tumor targeting cells. Extracorporeal PBMNC coating may be an option to control intravascular cytokine release induced by therapeutic antibodies. PMID- 17273870 TI - Abiotic-stress induces demethylation and transcriptional activation of a gene encoding a glycerophosphodiesterase-like protein in tobacco plants. AB - To examine the relationship between gene expression and DNA methylation, transcriptionally activated genes were screened in hypomethylated transgenic tobacco plants expressing an anti-DNA methyltransferase sequence. Among 16 genes initially identified, one clone was found to encode a glycerophosphodiesterase like protein (NtGPDL), earlier reported to be responsive to aluminium stress. When detached leaves from wild type tobacco plants were treated with aluminium, NtGPDL transcripts were induced within 6 h, and corresponding genomic loci were demethylated at CCGG sites within 1 h. Direct bisulfite methylation mapping revealed that CG sites in coding regions were selectively demethylated, and that promoter regions were totally unmethylated regardless of the stress. Salt and low temperature treatments also induced similar demethylation patterns. Such effects could be attributable to oxidative stress, since reactive oxygen species generated by paraquat efficiently induced the same pattern of demethylation at coding regions. Pathogen infection induced neither transcripts nor genomic demethylation. These results suggested a close correlation between methylation and expression of NtGPDL upon abiotic stresses with a cause-effect relationship. Since DNA methylation is linked to histone modification, it is conceivable that demethylation at coding regions might induce alteration of chromatin structure, thereby enhancing transcription. We propose that environmental responses of plants are partly mediated through active alteration of the DNA methylation status. PMID- 17273871 TI - Effects of postural task requirements on the speed-accuracy trade-off. AB - We investigated the speed-accuracy trade-off in a task of pointing with the big toe of the right foot by a standing person that was designed to accentuate the importance of postural adjustments. This was done to test two hypotheses: (1) movement time during foot pointing will scale linearly with ID during target width changes, but the scaling will differ across movement distances; and (2) variations in movement time will be reflected in postural preparations to foot motion. Ten healthy adults stood on the force plate and were instructed to point with the big toe of the right foot at a target (with widths varying from 2 to 10 cm) placed on the floor in front of the subject at a distance varying from 10 to 100 cm. The instruction given to the subjects was typical for Fitts' paradigm: "be as fast and as accurate as possible in your pointing movement". The results have shown that movement time during foot pointing movements scaled with both target distance (D) and target width (W), but the two dependences could not be reduced to a single function of W/D, confirming the first hypothesis. With respect to the second hypothesis, we found that changes in task parameters led to proportional variations in movement speed and indices of variability of the postural adjustments prior to leg movement initiation, confirming the second hypothesis. Both groups of observations were valid over the whole range of distances despite the switch of the movement strategy in the middle of this range. We conclude that the speed-accuracy trade-off in a task with postural adjustments originates at the level of movement planning. The different dependences of movement time on D and W may be related to spontaneous postural sway (migration of the point of application of the resultant force acting on the body of the standing person). The results may have practical implications for posture and gait rehabilitation techniques that use modifications of stepping accuracy. PMID- 17273872 TI - Behavioral dynamics of intercepting a moving target. AB - From matters of survival like chasing prey, to games like football, the problem of intercepting a target that moves in the horizontal plane is ubiquitous in human and animal locomotion. Recent data show that walking humans turn onto a straight path that leads a moving target by a constant angle, with some transients in the target-heading angle. We test four control strategies against the human data: (1) pursuit, or nulling the target-heading angle beta, (2) computing the required interception angle beta (3) constant target-heading angle, or nulling change in the target-heading angle beta and (4) constant bearing, or nulling change in the bearing direction of the target psi which is equivalent to nulling change in the target-heading angle while factoring out the turning rate (beta - phi) We show that human interception behavior is best accounted for by the constant bearing model, and that it is robust to noise in its input and parameters. The models are also evaluated for their performance with stationary targets, and implications for the informational basis and neural substrate of steering control are considered. The results extend a dynamical systems model of human locomotor behavior from static to changing environments. PMID- 17273873 TI - Interference to consolidation phase gains in learning a novel movement sequence by handwriting: dependence on laterality and the level of experience with the written sequence. AB - Practice on a novel sequence of movements can lead to two behavioral expressions of procedural memory consolidation processes: delayed performance gains evolving hours after the termination of training, but also a decrease in the susceptibility of the training-related gains to interference by subsequent experience within a few hours following training. It is not clear what types of experience constitute effective interference for a given task. We recently showed that the handwriting of words in a well-practiced script immediately after training on the finger opposition sequence (FOS) learning task interfered with the expected delayed gains. Here, in Experiment 1, we compared the degree of interference, on FOS learning with the left or the right hand, exerted by writing common words using the right, dominant, hand. Robust interference occurred only when practice in the FOS and the subsequent handwriting were performed with the same hand. In Experiment 2 we tested whether the level of experience with the writing sequence affected the degree of interference on FOS learning. As opposed to writing common words, there was no interference to the FOS gains by writing non-words, composed of the same letters as the common words, even when both tasks were executed with the same hand. Given that interference occurs when there is a critical overlap between the neuronal representations of two tasks, our results indicate that the extent of overlap between the representations is related, at least in part, to motor lateralization and to the level of experience with the interfering task. PMID- 17273874 TI - Beta- and gamma-frequency coupling between olfactory and motor brain regions prior to skilled, olfactory-driven reaching. AB - A major question in neuroscience concerns how widely separated brain regions coordinate their activity to produce unitary cognitive states or motor actions. To investigate this question, we employed multisite, multielectrode recording in rats to study how olfactory and motor circuits are coupled prior to the execution of an olfactory-driven, GO/NO-GO variant of a skilled, rapidly executed (approximately 350-600 ms) reaching task. During task performance, we recorded multi-single units and local field potentials (LFPs) simultaneously from the rats' olfactory cortex (specifically, the posterior piriform cortex) and from cortical and subcortical motor sites (the caudal forepaw M1, and the magnocellular red nucleus, respectively). Analyses on multi-single units across areas revealed an increase in beta-frequency spiking (12-30 Hz) during a approximately 100 ms window surrounding the Final Sniff of the GO cue before lifting the arm (the "Sniff-GO window") that was seldom seen when animals sniffed the NO-GO cue. Also during the Sniff-GO window, LFPs displayed a striking increase in beta, low-gamma, and high-gamma energy (12-30, 30-50, and 50-100 Hz, respectively), and oscillations in the high gamma band appeared to be coherent across the recorded sites. These results indicate that transient, multispectral coherence across cortical and subcortical brain sites is part of the coordination process prior to sensory-guided movement initiation. PMID- 17273876 TI - Fatal bleeding from major femoral vessels: three case reports. AB - We present three unusual cases of fatal bleeding from eroded femoral blood vessels. Erosion was due to tumor metastases in one and abscess formation in two cases. Bleeding occurred from the femoral vein in two cases and from the femoral artery in one case. Extensive bloodstains at the death scene were suspicious of homicide, which was ruled out by medico-legal autopsy in all cases. PMID- 17273875 TI - Acute effects of naltrexone and GBR 12909 on ethanol drinking-in-the-dark in C57BL/6J mice. AB - RATIONALE: Recently, a simple procedure was described, drinking in the dark (DID), in which C57BL/6J mice self-administer ethanol to the point of intoxication. The test consists of replacing the water with 20% ethanol in the home cage for 2 or 4 h early during the dark phase of the light/dark cycle. OBJECTIVES: To determine whether the model displays predictive validity with naltrexone, and whether opioid or dopaminergic mechanisms mediate excessive drinking in the model. MATERIALS AND METHODS: Naltrexone or GBR 12909 were administered via intraperitoneal injections immediately before offering ethanol solutions, plain tap water, or 10% sugar water to male C57BL/6J mice, and consumption was monitored over a 2- or 4-h period using the DID procedure. RESULTS: Naltrexone (0.5, 1, or 2 mg/kg) dose dependently decreased ethanol drinking but these same doses had no significant effect on the consumption of plain water or 10% sugar water. GBR 12909 (5, 10, and 20 mg/kg) dose dependently reduced the consumption of ethanol and sugar water but had no effect on plain water drinking. CONCLUSIONS: The DID model demonstrates predictive validity. Both opioid and dopamine signaling are involved in ethanol drinking to intoxication. Different physiological pathways mediate high ethanol drinking as compared to water or sugar water drinking in DID. DID may be a useful screening tool to find new alcoholism medications and to discover genetic and neurobiological mechanisms relevant to the human disorder. PMID- 17273877 TI - Complex variability of intron 40 of the von Willebrand factor (vWF) gene. AB - Intron 40 of the von Willebrand factor (vWF) gene exhibits a highly variable region of about 0.65 kb, which contains 5 juxtaposed STRs. We sequenced 0.65 kb amplicons from 68 chromosomes and found 2 frequent indel polymorphisms and 5 SNPs. The 68 chromosomes investigated here presented a total of 47 different haplotypes. Regarding the SNP allele distribution in our sample, we arranged our results of the vWF intron 40 into a system of 3 haplotypes, i.e. haplotypes a, b and c. Our review may be valuable in further optimising vWF typing in forensic applications and in avoiding pitfalls. Further attempts to develop sophisticated techniques may soon enable haplotyping using autosomale STR clusters. PMID- 17273878 TI - Proteome analysis of new antimalarial endoperoxide against Plasmodium falciparum. AB - N-89, a new antimalarial endoperoxide, was selected as a promising antimalarial compound showing high activity and selectivity. To study the mechanism of N-89 action, N-89 resistant strain (NRC10) was obtained by intermittent drug pressure. NRC10 had a tenfold increase in the EC(50) value of N-89. No cross-resistance was obtained with other antimalarial compounds. Comparative proteome analysis of N-89 sensitive and NRC10 strains revealed over-expression of 12 spots and down regulation of 14 spots in NRC10. Fifteen proteins were identified of Plasmodium falciparum origin. The identified proteins representing several functions, mainly related to the glycolytic pathway, and metabolism of protein and lipid. Our results suggest that identified proteins may be candidates of antimalarial endoperoxide targets. PMID- 17273879 TI - Model-based ankle joint angle tracing by cuff electrode recordings of peroneal and tibial nerves. AB - The main goal of the present study was to estimate the ankle joint angle from the peroneal and tibial electroneurography (ENG) recordings. Two single-channel cuff electrodes for recording ENG were placed on the proximal part of rabbit peroneal and tibial nerves respectively and static positioning and ramp-and-hold stretches were performed to characterize the static and dynamic ENG responses. An ENG model, consisting of static and dynamic parts, was constructed to relate ENG to ankle angle trajectory and an inverse ENG model was derived to predict ankle angle. The results showed that the new model could accurately estimate large range ankle angles during and after ramp-and-hold movements. Our study provides a basis for implementing joint angle tracing without using artificial angle sensors. PMID- 17273880 TI - Taxis equations for amoeboid cells. AB - The classical macroscopic chemotaxis equations have previously been derived from an individual-based description of the tactic response of cells that use a "run and-tumble" strategy in response to environmental cues [17,18]. Here we derive macroscopic equations for the more complex type of behavioral response characteristic of crawling cells, which detect a signal, extract directional information from a scalar concentration field, and change their motile behavior accordingly. We present several models of increasing complexity for which the derivation of population-level equations is possible, and we show how experimentally measured statistics can be obtained from the transport equation formalism. We also show that amoeboid cells that do not adapt to constant signals can still aggregate in steady gradients, but not in response to periodic waves. This is in contrast to the case of cells that use a "run-and-tumble" strategy, where adaptation is essential. PMID- 17273881 TI - Seroprevalence of vaccine preventable and blood transmissible viral infections (measles, mumps, rubella, polio, HBV, HCV and HIV) in medical students. AB - In the course of clinical training medical students are in particular exposed to infectious diseases. Therefore, the present study was performed to investigate the immunity status of 223 medical students in their first clinical semester to job-related diseases. Specific serological antibody testing of hepatitis B-virus (HBV), hepatitis C-virus (HCV), human immunodeficiency virus (HIV), varicella zoster- (VZV), measles-, mumps-, rubella and polioviruses' type 1, 2 and 3 were performed. The results yielded, that 69.5% of the students had an anti-HBs-level > or =10 IU/l and 54.7% > or =100 IU/l. Neither HCV infection nor HIV infection were found, but one student showed an active HBV infection. Virus specific immunity rates were found in 91.5% for measles, 80.3% for mumps, 90.1% for rubella and 96.9% for varicella. Furthermore the medical students demonstrated neutralizing antibodies to polioviruses: 95.1% (type 1), 96.9% (type 2) and 70% (type 3). 68.2% had antibodies (titer 1:> or =10) against all three virus types. The partly significant gaps of immunity in the students need to be closed prior to the first contact with patients. PMID- 17273882 TI - Deterioration of contractile properties of muscle fibres in elderly subjects is modulated by the level of physical activity. AB - The impact of ageing on force and velocity of human skeletal muscle fibres has been extensively studied. As discrepancies have been reported, it is still unclear whether or not a deterioration of the capacity of muscle fibres to develop force and shortening is involved in determining weakness and decrease in shortening velocity of skeletal muscle of elderly people. We compared myosin heavy chain (MHC) isoform distribution of vastus lateralis muscle, and specific force (Po/CSA) and maximum shortening velocity (Vo) of skeletal muscle fibres among one population of young controls (CTRL) and three populations of elderly (EL) subjects with very variable levels of physical activity: sedentary (EL-SED, n = 3); controls (EL-CTRL, n = 4); endurance trained (EL-END, n = 3). Muscle phenotype was progressively faster in the order EL-END --> CTRL --> EL-CTRL --> EL-SED. Po/CSA and Vo also varied among the different populations of elderly subjects generally showing a decreasing deterioration with increasing activity levels. The results suggest that discrepancies observed so far in age-induced deterioration of contractile properties of muscle fibres could depend on the different activity levels of the populations of elderly subjects enrolled in the studies. PMID- 17273883 TI - Evaluation of Margaria staircase test: the effect of body size. AB - The purpose of this study was to evaluate the methodology of Margaria staircase test (MT) for assessment of muscle anaerobic power. Specifically, we hypothesized that due to the scaling effects the outcome of MT calculated using the standard formula that suggests the power output to be proportional to body mass [P = (m . g . h)/T; P = power output, m = body mass, g = 9.81 m/s(2), h = height of stairs climbed, T = running time] overestimates the effect of body size on the calculated muscle power output. Young and physically active subjects (N = 111) were tested and the relationship between P and body size (S; either body mass or height) was assessed by standard allometric model (i.e., P = a . S ( b ); where a and b were the constant multiplier and allometric parameter, respectively). The results supported the hypothesized relationship by revealing b = 0.66 (95%CI = 0.49-0.83; r = 0.59; P < 0.001) and b = 1.13 (95%CI = 0.49-0.83; r = 0.34; P < 0.001) for body mass and body height, respectively. The obtained values of b (i.e., b < 1 for body mass and b < 3 for body height) suggest that the standard formula of MT overestimates the power output of larger subjects and underestimates the power of smaller ones. Since the results were mainly in line with both the experimental findings and theoretical predictions regarding the general effects of scale on human muscle power, we propose a modified formula that provides normalized power: P ( n ) = P/m (0.67) = [(m . g . h)/T]/m (0.67) = (m (0.33) . g . h)/T. The modified formula could provide a body size independent index of muscle power that would both allow for establishing standards and enable comparison of individuals and groups of individuals of different body dimensions. PMID- 17273885 TI - Predicting impairment of central vision from dimensions of the optic chiasm in patients with pituitary adenoma. AB - AIM: To study a possible relationship between dimensions of the optic chiasm and extent of visual field impairment in patients with pituitary adenoma. METHODS: Pre-operative magnetic resonance (MR) scans and Goldmann perimetry charts of patients having undergone resection of a pituitary adenoma were retrieved. Area of the chiasm (A (chiasm)), central height of the chiasm (H (chiasm)), and perpendicular height of tumour (H (tumour)) were measured on coronal images using standard software. Visual fields were quantified by subdividing the central 30 degrees of vision into 72 subunits each bounded by 15 degree meridians and 10 degree isoptres. RESULTS: Nineteen patients were included in this study. There was a strong statistically significant linear correlation between H (chiasm) and bitemporal (Pearson's coefficient r = -0.69, p = 0.001), binocular (r = -0.63, p = 0.004) and binasal (r = -0.52, p = 0.01) central field loss. A similar relationship was observed between H (tumour) and bitemporal (r = 0.55, p = 0.015) and binocular (r = 0.46, p = 0.05) central field loss. CONCLUSION: Height of the chiasm and height of the tumour can be used to predict extent of central visual impairment. PMID- 17273884 TI - Protein requirements in male adolescent soccer players. AB - Few investigations have studied protein metabolism in children and adolescent athletes which makes difficult the assessment of daily recommended dietary protein allowances in this population. The problematic in paediatric competitors is the determination of additional protein needs resulting from intensive physical training. The aim of this investigation was to determine protein requirement in 14-year-old male adolescent soccer players. Healthy male adolescent soccer players (N = 11, 13.8 +/- 0.1 year) participated in a short term repeated nitrogen balance study. Diets were designed to provide proteins at three levels: 1.4, 1.2 and 1.0 g protein per kg body weight (BW). Nutrient and energy intakes were assessed from 4 day food records corresponding to 4 day training periods during 3 weeks. Urine was collected during four consecutive days and analysed for nitrogen. The nitrogen balances were calculated from mean daily protein intake, mean urinary nitrogen excretion and estimated faecal and integumental nitrogen losses. Nitrogen balance increased with both protein intake and energy balance. At energy equilibrium, the daily protein intake needed to balance nitrogen losses was 1.04 g kg(-1) day(-1). This corresponds to an estimated average requirement (EAR) for protein of 1.20 g kg(-1) day(-1) and a recommended daily allowance (RDA) of 1.40 g kg(-1) day(-1) assuming a daily nitrogen deposition of 11 mg kg(-1). The results of the present study suggest that the protein requirements of 14-year-old male athletes are above the RDA for non-active male adolescents. PMID- 17273887 TI - Petrous apex cholesterol granuloma treated via the endoscopic transsphenoidal approach. AB - Numerous surgical approaches have been used to treat petrous apex cholesterol granulomas. They are usually treated via the transtemporal- or middle fossa approach; some are managed endoscopically. We present a patient treated by the endoscopic transsphenoidal approach and review the literature. PMID- 17273886 TI - Intratumoral hemorrhage after remote subtotal microsurgical resection and gamma knife radiosurgery for vestibular schwannoma. AB - Our report describes the occurrence of intratumoral hemorrhage in a vestibular schwannoma, which was treated with microsurgical resection thirteen years and gamma knife surgery (GKS) more than two years prior to the event. Although rare, it is apparent that bleeding into a vestibular schwannoma remains a possibility, even after the tumor has responded favorably to GKS. Long-term followup of patients with vestibular schwannoma who have been treated with GKS is advisable to assess treatment response and to detect adverse events (e.g. hemorrhage) suspected on clinical grounds. PMID- 17273888 TI - Leptomeningeal cyst due to vacuum extraction delivery in a twin infant. AB - A rare case of a leptomeningeal cyst is reported in a twin male neonate delivered using a vacuum extractor, who presented a huge, non-pulsating, oedematous mass overlying the frontal fontanelle after birth. The mass was initially diagnosed as a cephalo haematoma. Ultrasonography indicated intracranial bleeding and a subsequent CT scan revealed an intraparenchymal bleeding above the left frontal horn, combined with a thin, left-sided, subdural haematoma and subarachnoid haemorrhage in the left Sylvian fissure. Apart from a bulging soft and round formation (2 x 2 x 3 cm) next to the anterior fontanel growing since birth, the neurological development of the infant was normal. MRI examination at the age of 7 months revealed that it consisted of a cystic mass (leptomeningeal cyst) connected to the left frontal horn, stretching right through the brain and also penetrating the dura mater. No signs of the perinatal haematomas were observed at this time. Surgical treatment, with fenestration of the cyst into the frontal horn and a watertight duraplasty with a periosteal flap and thrombin glue covered by small bone chips, was performed at 9 months of age. Due to a residual skull bone defect a second cranioplasty with autologous skull bone was performed three and half years later. During a follow-up period of 12 years the neurological and psychological development of the boy has been indistinguishable to that of his twin brother, indicating the satisfactory outcome of the treatment. PMID- 17273889 TI - Prognosis factors of survival time in patients with glioblastoma multiforme: a multivariate analysis of 340 patients. AB - BACKGROUND: The prognosis of glioblastoma multiforme remains poor despite recent therapeutic advances. Several clinical and therapeutic factors as well as tumour characteristics have been reported as significant to survival. A more efficient determination of the prognostic factors is required to optimize individual therapeutic management. The aim of our study was to evaluate by univariate then multivariate analysis the factors that influence prognosis and particularly survival. METHODS: Data of 340 patients with newly-diagnosed GBM were retrospectively analyzed. Univariate analysis of prognosis factors of survival time was performed. Factors that seemed determinant were evaluated by Kaplan Meier survival curves. Finally, the significant factors found in univariate analysis were tested in multivariate analysis using the COX regression method. FINDINGS: Using multivariate analysis, the following factors were found to influence survival: radiotherapy was the predominant factor followed by radical surgery, tumour location, age and chemotherapy. Patients treated with temozolomide had a markedly better survival rate than patients treated with other chemotherapies (Log-rank test P < 0.005). The values of GBM type (de novo or secondary), as well as repeated surgery and partial surgery (vs. simple biopsy) were suggested by univariate analysis but not confirmed by the COX regression method. After radical surgery, progression-free survival was correlated to overall survival (r = 0.87, P < 10e-5). CONCLUSIONS; The influence of radiotherapy on survival was greater than the influence of age, an argument supporting the proposition of radiotherapy for patients until at least age 70. In the case of recurrence, the correlation between overall survival and progression free survival is an important factor when considering the therapeutic options. Initial radical surgery and repeated procedures dramatically influence survival. The benefit of partial surgery remains difficult to evaluate. Partial surgery could be used to decrease intracranial pressure and to minimize residual tumours in order to enable treatment by chemotherapy and radiotherapy. The value of temozolomide treatment was confirmed. PMID- 17273890 TI - Risk factors for the association of intracranial and aortic aneurysms. AB - This study investigated the association of intracranial aneurysms and abdominal aortic aneurysms to elucidate the incidence and independent risk factors for this association. Ultrasonography of the abdominal aorta was performed in 181 patients with 224 intracranial aneurysms. Six patients had suffered subarachnoid haemorrhage and the others had chronic disease or no symptoms. Magnetic resonance angiography was performed for confirmation if abdominal aortic aneurysm was identified by ultrasonography. Thirteen patients (7.2%) with 23 intracranial aneurysms had abdominal aortic aneurysms. Univariate analysis demonstrated that age (p < 0.01), size of intracranial aneurysms (p < 0.001), male sex (p < 0.01), multiplicity of intracranial aneurysms (p < 0.001), history of cerebrovascular diseases (p < 0.05), and current smoking (p < 0.0001) were significantly different between patients with and without this association. Multiple logistic analysis indicated that age (odds ratio [OR] 1.27, 95% confidence interval 1.08 1.48, p < 0.01), multiplicity (OR 22.1, 95% confidence interval 1.83-266.3, p = 0.01), size of intracranial aneurysms (OR 1.30, 95% confidence interval 1.10 0.54, p < 0.01), and current smoking (OR 33.3, 95% confidence interval 2.43 456.7, p = 0.01) were independent risk factors for the association. Patients with intracranial aneurysms who are older males with multiple or large intracranial aneurysms, and current smokers should be examined for abdominal aortic aneurysms using ultrasonography. PMID- 17273891 TI - Inhibition of hepatitis C virus replication and expression by small interfering RNA targeting host cellular genes. AB - Small interfering RNA (siRNA) is a powerful tool for functional genomics and gene therapy. Viral replication and gene expression are strongly inhibited by siRNA treatment of infected mammalian cells. However, the high sequence specificity of siRNAs, combined with prolonged treatment, promote the emergence of siRNA resistant virus variants, especially among viruses that encode a polymerase lacking proofreading capabilities, indicating that the antiviral properties of specific siRNAs are not as effective as expected. To investigate the silencing effect of siRNAs against selected host cellular proteins that promote replication of hepatitis C virus (HCV), several siRNAs against human VAMP-associated protein (hVAP-A), La antigen and polypyrimidine-tract-binding protein (PTB) were evaluated. The data show that several siRNAs markedly decreased the expression levels of corresponding cellular genes that inhibited HCV replication in Huh-7 cells. These treatments were also shown to have no impact upon cell viability. These findings provide an alternative approach for blocking HCV replication. Hence, combination therapies with siRNAs against both the virus and host genes that support virus replication are likely to be a potent approach in the treatment of chronic hepatitis C. PMID- 17273892 TI - DNA banking for plant breeding, biotechnology and biodiversity evaluation. AB - The manipulation of DNA is routine practice in botanical research and has made a huge impact on plant breeding, biotechnology and biodiversity evaluation. DNA is easy to extract from most plant tissues and can be stored for long periods in DNA banks. Curation methods are well developed for other botanical resources such as herbaria, seed banks and botanic gardens, but procedures for the establishment and maintenance of DNA banks have not been well documented. This paper reviews the curation of DNA banks for the characterisation and utilisation of biodiversity and provides guidelines for DNA bank management. It surveys existing DNA banks and outlines their operation. It includes a review of plant DNA collection, preservation, isolation, storage, database management and exchange procedures. We stress that DNA banks require full integration with existing collections such as botanic gardens, herbaria and seed banks, and information retrieval systems that link such facilities, bioinformatic resources and other DNA banks. They also require efficient and well-regulated sample exchange procedures. Only with appropriate curation will maximum utilisation of DNA collections be achieved. PMID- 17273894 TI - Temporal and spatial expression analysis of gamma kafirin promoter from Sorghum (Sorghum bicolor L. moench) var. M 35-1. AB - Different cis acting elements of gamma kafirin gene from Sorghum bicolor var. M 35-1 were amplified and cloned using different combination of the primers. The amplified promoter was replaced with CaMV35S promoter of vector pCMBIA-1304 and resultant vector contained beta-glucuronidase (gus) gene under the control of amplified gamma-kafirin promoter. The resulting fusants were then transformed in to different explants of sorghum via particle bombardment. The regulation of uid gene expression was analyzed to find out the minimum required 5' regulatory sequence and cis acting elements for the efficient expression. However no gus expression was detected in leaves of micropropagated plants, scutellum and calli at any stage of growth. The expression of gus, with pKaf gus-P4 gene construct, was detected in immature embryos and endosperm 20 days after pollination (DAP). The result suggest that at least three motifs (two GCN4 and one prolamin box) besides TATA and CATC boxes are required for the efficient expression of the kafirin gene of sorghum. The study shows that PCR based isolation of different motifs and regions can be used as an alternate to deletion analysis for observing the role of various motifs and their importance in the gene expression and regulation. PMID- 17273895 TI - Landscape controls on mercury in streamwater at Acadia National Park, USA. AB - Fall and spring streamwater samples were analyzed for total mercury (Hg) and major ions from 47 locations on Mount Desert Island in Maine. Samples were collected in zones that were burned in a major wildfire in 1947 and in zones that were not burned. We hypothesized that Hg concentrations in streamwater would be higher from unburned sites than burned watersheds, because fire would volatilize stored Hg. The Hg concentrations, based on burn history, were not statistically distinct. However, significant statistical associations were noted between Hg and the amount of wetlands in the drainage systems and with streamwater dissolved organic carbon (DOC). An unexpected result was that wetlands mobilized more Hg by generating more DOC in total, but upland DOC was more efficient at transporting Hg because it transports more Hg per unit DOC. Mercury concentrations were higher in samples collected at lower elevations. Mercury was positively correlated with relative discharge, although this effect was not distinguished from the DOC association. In this research, sample site elevation and the presence of upstream wetlands and their associated DOC affected Hg concentrations more strongly than burn history. PMID- 17273893 TI - Quantitative ultrasound predicts hip and non-spine fracture in men: the MrOS study. AB - Quantitative ultrasound (QUS) is associated with fracture risk in women, but there are few data in men. We studied 5,607 older men and found that QUS predicts hip and any non-spine fracture risk nearly as well as BMD. Combined measurements of QUS and BMD are not superior to either measurement alone. INTRODUCTION: Quantitative ultrasound (QUS) predicts fracture risk among older women, but there are few prospective studies among older men. We studied the ability of QUS and BMD measurements to predict hip and other non-spine fractures in a population based study of older men. METHODS: Calcaneal QUS and hip BMD were measured in 5,607 men aged > or =65 years recruited from six US centers. At baseline duplicate QUS measurements with repositioning were obtained, and subsequent hip and other non-spine fractures were documented by review of x-rays or x-ray reports. The relationships between QUS and fractures were examined with proportional hazard models adjusted for age and clinic. We used receiver operating characteristic curves and predicted fracture risk models to determine the utility of QUS alone, BMD alone or the combination of QUS+BMD. RESULTS: During a mean follow-up of 4.2 years with 99% complete follow-up, 239 men suffered a non-spine fracture, including 49 hip fractures. Each standard deviation reduction in broadband ultrasonic attenuation (BUA) was associated with an increased risk of hip (relative hazard=2.0, CI: 1.5, 2.8) and any non-spine fracture (relative hazard=1.6, CI: 1.4, 1.8). The area under the receiver operating characteristic curve and the predicted probability of fracture were similar for BUA alone, BMD alone and the combination of BUA+BMD, indicating that once BUA or BMD is known, the other measurement does not add useful information. Other QUS parameters gave similar results. CONCLUSIONS: QUS measurements predict the risk of hip and any non-spine fracture in older men, and do so nearly as well as hip BMD measurements. Combined measurements of QUS and BMD are not superior to either measurement alone. PMID- 17273897 TI - Evaluation of the effectiveness of posters to provide information to patients about a DNA database and their opportunity to opt out. AB - OBJECTIVE: Vanderbilt University Medical Center is implementing a DNA Databank to facilitate genomic research. This study describes the use of informational posters to communicate to patients about the Databank and their option to not participate. METHODS: Informational posters were displayed in two phlebotomy areas prior to the implementation of the DNA Databank project. Patients leaving the phlebotomy areas were interviewed by non-medical personnel about the posters and the Databank using a structured interview guide. RESULTS: Completed interviews with patients (n = 192) show that only 32% recalled seeing the posters (memory of the image only, or of the image and the content of the text). The majority of participants (93%) either recalled the poster or reported that they were comfortable with the DNA Databank concept after they had been read a brief statement about the program. A significant relationship (p = 0.001) appeared between respondents' awareness of research practices concerning anonymous discarded tissues and their level of comfort with the DNA Databank. CONCLUSIONS: Individuals who report feeling uncomfortable with the Databank are an important population to inform about the Databank and opting out. Since there were no statistically significant demographic differences between those who recalled the poster and those who did not, there is no way to prospectively identify which patients will not be reached by the posters or who may feel uncomfortable with the program. Additional mechanisms to promote widespread notification are needed. PMID- 17273896 TI - Nutrient export from watersheds on Mt. Desert Island, Maine, as a function of land use and fire history. AB - A study of 13 small (less than 7.5 km(2)) watersheds on Mt. Desert Island, Maine, was conducted from January 1999 to September 2000 to determine nutrient export delivery to coastal waters around the island, and to determine whether a series of wildfires in 1947 have affected nutrient export in burned watersheds. Nutrient export (nitrate-nitrogen, total nitrogen, total phosphorus) was determined for each watershed during the study period, and was normalized by watershed area. The yield of nitrate-nitrogen (N) ranged from 10 to 140 kg/km(2)/year. Total N yield ranged from 42 to 250 kg/km(2)/year. Total phosphorus (P) yield ranged from 1.4 to 7.9 kg/km(2)/year. Watersheds entirely within Acadia National Park (lacking human land-based nutrient sources) exported significantly less total N and total P than watersheds that were partly or entirely outside the park boundary. Nitrate N export was not significantly different in these two groups of watersheds, perhaps because atmospheric deposition is a dominant source of nitrate in the study area. No relation was observed between burn history and nutrient export. Any effect of burn history may be masked by other landscape-level factors related to nutrient export. PMID- 17273898 TI - Deep-freeze preservation of cranial bones for future cranioplasty: nine years of experience in Soroka University Medical Center. AB - BACKGROUND: Decompressive craniectomy is routinely performed in many neurosurgical centers to treat intracranial hypertension refractory to medical therapy as a result of head trauma, CVA or various brain tumors. When the patient survives his illness, cranioplasty with autologous bone graft or other reconstructive materials is considered to repair the skull defect. OBJECTIVE: This prospective study reviews the cases of decompressive craniectomies followed by later cranioplasty undertaken at our institute through the years 1996 and 2005 and describes the method used for preservation of removed bone flaps for future cranioplasty. SUBJECTS AND METHODS: Sixty-eight patients underwent decompressive craniectomies since 1996. A protocol was designed to prepare the removed bone flaps for deep freeze preservation. After removal, the bone flaps were transferred to the skin bank at our institution within 6 h, gently rinsed using 1 3 liters of sterile saline (0.9% NaCl) supplemented with antibiotics (neomycin, 2 mM) with no dimethylsulfoxide (DMSO), then flaps were wrapped in two layers of sterile plastic coverage and preserved at -80 degrees C. RESULTS: The patient's population will be presented. Since 1996 we have performed 12 cranioplasties using deep-freeze preserved autologous bone graft. It took a rather long learning period, beginning with a single patient per year and continued with several others. Up to now, no case of infection, osteomyelitis or bone resorption following cranioplasty have occurred. CONCLUSION: Deep-freeze preservation of autologous bone grafts to reconstruct skull defects after decompressive craniectomy is a useful procedure and has a low revision rate. PMID- 17273899 TI - Characterization of Japanese flounder karyotype by chromosome bandings and fluorescence in situ hybridization with DNA markers. AB - The chromosomes of Japanese flounder, Paralichthys olivaceus, were examined by conventional differential staining methods including G-, Q-, C-, silver (Ag)-, fluorochrome, and replication R-bandings and by fluorescence in situ hybridization (FISH) with 5S and 18S rDNAs and telomeric DNA as probes. Replication R-banding substantially made it possible to identify 24 homologous pairs by their RBG-banding pattern and relative length. Both rDNA loci were mapped to chromosome 1, where 5S and 18S rDNA loci were located at the centromeric region and secondary constriction, respectively. C-banding revealed that both rDNA loci were heterochromatic, and 18S rDNA loci were positive for chromomycin A(3) but negative for 4',6-diamidino-2-phenylindole (DAPI) staining. Telomeric FISH signals were observed at all chromosome ends and at the interstitial region of some chromosomes. The observed results were discussed in relation to the karyotype evolution in the order Pleuronectiformes. PMID- 17273900 TI - Peptidoglycan enhances transcriptional expression of CCAAT/enhancer-binding protein delta gene in mouse macrophages. AB - Peptidoglycan-activated gene expression is mediated through various transcription factors including CCAAT/enhancer-binding protein delta (C/EBPdelta). The purpose of the present study is to elucidate the mechanism of PGN-activated C/EBPdelta gene. PGN stimulated C/EBPdelta protein and mRNA expression in mouse macrophages RAW 264.7 cells. Analysis of C/EBPdelta promoter activity by luciferase reporter assay indicated that PGN-induced C/EBPdelta gene activation is partially mediated by the -345 to +24 bp of C/EBPdelta gene promoter. The in vitro protein-DNA binding assay showed that Sp1, c-Rel and c-Jun are the major protein binding to this PGN-response element of C/EBPdelta promoter, and the binding of c-Rel and c Jun is increased after PGN treatment. All of these binding activities were abolished when Sp1-, NF-kappaB/APRE-, CRE-sites were mutated. Furthermore, analysis of this promoter region by site-directed mutants constructed in luciferase reporter vector indicated that two Sp1-sites, one NF-kappaB/APRE-site and one CRE-site are prominent for PGN-induced gene expression. In addition, when Sp1, c-Rel or c-Jun transcription factors were overexpressed in cells, all of them enhanced C/EBPdelta promoter activity. In summary, we suggest that Sp1, c Rel and c-Jun transcription factors play important roles in activation of C/EBPdelta gene promoter under the stimulation of PGN. Given the importance of C/EBPdelta in inflammatory disease, these results reveal a clue as a potential therapeutic target for suppression of C/EBPdelta expression under PGN stimulation. PMID- 17273901 TI - Squamous cell carcinoma of the male bulbomembranous (proximal) urethra--how should the treatment be done? A case report and review of the literature. AB - The probability of the squamous cell carcinoma of the male bulbomembranous urethra is rare. The patients generally diagnosed as urethral stenosis. It has a high stage because of the late symptoms and diagnosis. Monotherapy and multimodal treatments have been considered. Currently, the standard therapy has not been decided yet. PMID- 17273902 TI - Percutaneous versus transurethral cystolithotripsy and TURP for large prostates and large vesical calculi: refinement of technique and updated data. AB - BACKGROUND AND PURPOSE: We compare two modalities of treatment; transurethral cystolithotripsy (TUCL) and percutaneous cystolithotripsy (PCCL), for large vesical calculi in patients who underwent simultaneous transurethral resection of prostate (TURP), and present refinements of the technique of PCCL. PATIENTS AND METHODS: Between July 1999 and June 2003, 54 patients were subjected to either TUCL (n = 19) or PCCL (n = 35) along with simultaneous TURP. Inclusion criteria were prostate volume > 50 ml, aggregate stone size > 3 cm with each individual stone > 1 cm, In the TUCL group, calculi were treated with 26F nephroscope, pneumatic lithotripsy and fragment extraction. This was followed by TURP with 26F continuous-flow resectoscope. In the PCCL group, calculi were removed through a suprapubic 30F Amplatz sheath followed by standard TURP with the suprapubic sheath in situ to provide continuous drainage. A 20F two-way Foley catheter was inserted suprapubically and urethrally in cases of PCCL and a 22-24F three-way catheter urethrally after TUCL. RESULTS: The two groups were comparable in age. The mean prostate size as well as aggregate stone size was significantly larger in PCCL group. The operating time for stone removal was significantly less in the PCCL group while time required for TURP was statistically similar in two groups. In the TUCL arm three patients had residual stones requiring repeat TUCL, and one developed a urethral stricture. CONCLUSIONS: Combined TURP and PCCL is safe, more effective and a much faster alternative to combined TURP and TUCL in patients with large bladder calculi and large prostates. PMID- 17273903 TI - Retinal fluorescein and indocyanine green angiography and optical coherence tomography in successive stages of Vogt-Koyanagi-Harada disease. AB - OBJECTIVE: To report features of retinal fluorescein (FA) and indocyanine green (ICGA) angiography and optical coherence tomography (OCT) at successive stages of Vogt-Koyanagi-Harada (VKH) disease. METHODS: FA and ICGA were systematically performed in cases of VKH disease, at admission, 1 month later, and at the end of the follow-up. In addition, the most recent patients underwent OCT. In the follow up, the clinical evolution and extent of treatment were related to the angiographic and tomographic features. RESULTS: FA and ICGA showed a diffuse delayed choroidal perfusion, including a delayed arterial, choriocapillar, and venous filling. This delayed choroidal perfusion involved the posterior pole and the hole periphery. The classically described serous retinal detachments were slowly filled from numerous pin points that could correspond to leakage through areas of damaged retinal pigment epithelium due to the choroidal ischemia. An uneven background choroidal fluorescence visible at the mid phase of ICGA was the result of multiple hypofluorescent round lesions in the choroidal stroma. Choroidal folds appeared hypofluorescent in FA and hyperfluorescent in ICGA. Some of these angiographic findings were present at the very early neurologic stage of the disease. Moreover, under treatment, a persisting altered choroidal perfusion could increase the incidence of retinal detachment relapses. DISCUSSION: Various pathological conditions are characterized by choroidal involvement and serous retinal detachment. Angiographical findings may be helpful in the diagnosis. CONCLUSION: FA coupled with ICGA can be an useful tool in the early diagnosis of VKH disease as well as during the tapering of immunosuppressive drugs. PMID- 17273904 TI - Retinal break following an intravitreal triamcinolone acetonide injection. AB - PURPOSE: To report a case of an unusual localization of retinal break following intravitreal triamcinolone acetonide (IVTA) injection. SUBJECTS AND METHODS: A 58 year-old male patient was admitted to our department for visual loss lasting more than 6 months. The patient was diagnosed as having proliferative diabetic retinopathy and diffuse macular edema. Therapy in the form of IVTA injection was given. RESULTS: During the first follow-up examination, 1 week after the IVTA injection, a retinal break with an attached flap on the nasal retinal area was observed. The retinal break was covered with laser photocoagulation. CONCLUSION: Although a rare possibility, a careful retinal examination during the follow-up period after IVTA injection may prevent retinal detachment. PMID- 17273906 TI - Disposal of unwanted medicines from households in Kuwait. AB - OBJECTIVE: To test the effectiveness of a simple educational intervention to encourage households to return unwanted medicines via a municipal collection program and to investigate the most common sources and types of unwanted medicines in the home. SETTING: Households in Kuwait City, Kuwait. METHOD: A convenience sample of 200 households in Kuwait received an educational letter and special plastic bags in which to place unwanted medicines to be collected by the municipality. They also completed a short self-administered questionnaire on medicine disposal habits. A second convenience sample of an additional 14 households in Kuwait received the same educational letter together with a face-to face interview and assistance in collecting unwanted medicines. Returned medicines were categorized and their source and expiry dates noted. MAIN OUTCOME MEASURE: Quantity and types of medicines returned. RESULTS: No medicines were collected from the 200 households participating in the municipal collection scheme in spite of 45% of respondents agreeing that this was an appropriate method of disposal. 97% of the respondents said they currently disposed of their medication in the garbage. The second intervention yielded 123 medicines from 14 homes, a third of which were for the respiratory system (38% of these were cough and cold preparations). The majority of returned medications were for acute conditions, almost all were from government health centers and 52% were expired. CONCLUSION: Simple collection of unwanted medicines by municipal authorities is unlikely to be effective. A multifaceted approach is more effective but resource intensive. Using local pharmacies as collection points in a reverse distribution system may be more cost-effective. PMID- 17273909 TI - Prophylactic naked DNA vaccination with the human vascular endothelial growth factor induces an anti-tumor response in C57Bl/6 mice. AB - Passive immunotherapy against soluble pro-angiogenic factors and/or their receptors in endothelial cells has become a promising approach in cancer therapeutics. There is also experimental evidence indicating that an active immunotherapy strategy directed towards these target molecules could also be effective. In this paper we show that it is possible to reduce tumor growth or increase the survival of tumor-bearing C57Bl/6 mice when animals are vaccinated with the human vascular endothelial growth factor (VEGF) isoform 121 gene (hVEGF(121)), and later challenged with melanoma or lung carcinoma tumor cells. Immunization was done with 10 microg DNA doses of the hVEGF121 gene, which is highly homologous to its mouse counterpart, administered on a weekly basis using a plasmid bearing 5 CpG bacterial motifs. Histopathology analyses of tumors of hVEGF(121) immunized animals showed a decrease in tumor cell density around vessels and in mitotic figures, as well as an increase in apoptotic tumor cells. A statistically significant cell cytotoxic response was found when spleen cells of immunized mice were co-cultured in vitro with mouse tumor VEGF-producing cells. Vaccination with an hVEGF121 gene mutated to make it deficient for VEGF receptor binding, produced similar in vitro and in vivo results, and significantly reduced the number of spontaneous metastases produced by the mouse Lewis lung carcinoma. Our results indicate that human VEGF DNA can be employed for anti-angiogenic active immunotherapy in mice, and that direct cell cytotoxicity is a contributor mechanism to the overall anti-tumor effects seen in immunized animals. PMID- 17273907 TI - Clinical and economic outcomes of pharmaceutical services related to antibiotic use: a literature review. AB - AIM OF THE REVIEW: To identify and review the clinical and economic impact of pharmacists' interventions on antibiotic use. METHOD: A literature search was conducted on Medline (1966-2003) to identify original articles measuring the impact of pharmacists' interventions on antimicrobial therapy at patient's or prescriber's level. RESULTS: Forty-three articles were included: 20 uncontrolled before-after studies, four controlled before-after studies, five controlled trials, 12 randomized controlled trials and two interrupted time series (ITS). The described interventions were grouped into four categories: patient-specific recommendations (pharmacists' interventions concerning patient-specific drug therapy), implementation of policies, education, and therapeutic drug monitoring. These interventions were often combined to provide a multifaceted intervention, making it difficult to isolate the impact of one specific intervention. Measured outcomes were: appropriateness of prescribing (evaluated in 17 studies, 16 showing significant improvement), costs (analysed in 22 studies, nine showing a statistically significant reduction in costs after or with the intervention), and length of hospital stay (mixed results). Other measured outcomes were: drug use, prescriptions, length of treatment, dose intervals, switch to oral route, mortality rate, and treatment failure. CONCLUSION: Over the years, the number of studies and quality of methodology has increased. The most frequently observed outcomes with a positive impact were appropriateness of prescribing and cost savings. The vast majority of studies used multiple interventions, in conjunction with pharmacists' recommendations to physicians. Coupled with the use of practice guidelines or educational strategies, these interventions demonstrated a positive impact on economic or clinical outcomes. However, the data are still sparse and sometimes contradictory; therefore, further studies with randomized controlled designs are needed. PMID- 17273910 TI - Upregulation of TNF-alpha production by IFN-gamma and LPS in cultured canine keratinocytes: application to monosaccharides effects. AB - Activated keratinocytes play a key role in the cutaneous immune system by their interactions with other cell types through the production of cytokines with both autocrine and paracrine activity. But there is little knowledge about epidermal cytokines in the dog. In this study, cultured canine keratinocytes were stimulated by human recombinant interferon gamma (IFN-gamma) and lipopolysaccharide (LPS) and cell supernatants were tested for tumour necrosis factor alpha (TNF-alpha) concentration using a cell viability assay on a murine cell line. We show that IFN-gamma in combination with LPS significantly increases TNF-alpha secretion by canine keratinocytes. The best stimulations were obtained using confluent cultures and the association of IFN-gamma (400 ng/ml) and LPS (40 microg/ml). The experimental protocol we describe represents a new method for studying keratinocyte activation and its modulation in the dog. We provide an example of application of our method: the study of the effects of different monosaccharides on canine keratinocyte activation. PMID- 17273911 TI - Plasma concentrations, pharmacokinetics and urinary excretion of gatifloxacin after single intravenous injection in buffalo calves. AB - The pharmacokinetics and urinary excretion of gatifloxacin were investigated after a single intravenous injection of 4 mg/kg body weight in buffalo calves. The therapeutic plasma drug concentration was maintained for up to 12 h. Gatifloxacin rapidly distributed from blood to tissue compartments, which was evident from the high values of the distribution rate constant, alpha1 (11.1 +/- 1.06 h(-1)) and the rate constant of transfer of drug from central to peripheral compartment, k12 (6.29 +/- 0.46 h(-1)). The area under the plasma drug concentration-time curve and apparent volume of distribution were 17.1 +/- 0.63 (microg.h)/ml and 3.56 +/- 0.95 L/kg, respectively. The elimination half-life (t (1/2 beta)), total body clearance (ClB) and the ratio of drug present in tissues and plasma (T/P) were 10.4 +/- 2.47 h, 235.1 +/- 8.47 ml/(kg.h) and 10.1 +/- 2.25, respectively. About 19.7% of the administered drug was excreted in urine within 24 h. A satisfactory intravenous dosage regimen for gatifloxacin in buffalo calves would be 5.3 mg/kg at 24 h intervals. PMID- 17273912 TI - Comparative pharmacokinetics of gentamicin after intravenous, intramuscular, subcutaneous and oral administration in broiler chickens. AB - The pharmacokinetics and bioavailability of gentamicin sulphate (5 mg/kg body weight) were studied in 50 female broiler chickens after single intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.) and oral administration. Blood samples were collected at time 0 (pretreatment), and at 5, 15 and 30 min and 1, 2, 4, 6, 8, 12, 24 and 48 h after drug administration. Gentamicin concentrations were determined using a microbiological assay and Bacillus subtillis ATCC 6633 as a test organism. The limit of quantification was 0.2 microg/ml. The plasma concentration-time curves were analysed using non-compartmental methods based on statistical moment theory. Following i.v. administration, the elimination half life (t (1/2beta)), the mean residence time (MRT), the volume of distribution at steady state (V (ss)), the volume of distribution (V (d,area)) and the total body clearance (Cl(B)) were 2.93 +/- 0.15 h, 2.08 +/- 0.12 h, 0.77 +/- 0.05 L/kg, 1.68 +/- 0.39 L/kg and 5.06 +/- 0.21 ml/min per kg, respectively. After i.m. and s.c. dosing, the mean peak plasma concentrations (C (max)) were 11.37 +/- 0.73 and 16.65 +/- 1.36 microg/ml, achieved at a post-injection times (t (max)) of 0.55 +/ 0.05 and 0.75 +/- 0.08 h, respectively. The t (1/2beta) was 2.87 +/- 0.44 and 3.48 +/- 0.37 h, respectively after i.m. and s.c. administration. The V (d,area) and Cl(B) were 1.49 +/- 0.21 L/kg and 6.18 +/- 0.31 ml/min per kg, respectively, after i.m. administration and were 1.43 +/- 0.19 L/kg and 4.7 +/- 0.33 ml/min per kg, respectively, after s.c. administration. The absolute bioavailability (F) of gentamicin after i.m. administration was lower (79%) than that after s.c. administration (100%). Substantial differences in the resultant kinetics data were obtained between i.m. and s.c. administration. The in vitro protein binding of gentamicin in chicken plasma was 6.46%. PMID- 17273913 TI - Transformation and fate of 2,4,6-trinitrotoluene (TNT) in anaerobic bioslurry reactors under various aeration schemes: implications for the decontamination of soils. AB - Energetic compounds have been used in a variety of industrial and military applications worldwide leading to widespread environmental contamination. Many of these compounds are toxic and resist degradation by oxidative enzymes resulting in a need for alternative remediation methods. It has been shown that trinitrotoluene (TNT)-contaminated soil subjected to treatment in strictly anaerobic bioreactors results in tight binding of TNT transformation products to soil organic matter. The research presented here examined the fate of TNT and its metabolites in bioreactors under three different aeration regimes. In all treatment regimes, the typical metabolites of aminodinitrotoluenes and diaminonitrotoluenes were observed prior to irreversible binding into the soil fraction of the slurry. Significant transformation of TNT into organic acids or simple diols, as others report in prior work, was not observed in any of the treatments and is an unlikely fate of TNT in anaerobic soil slurries. These results indicate that aeration does not dramatically affect transformation or fate of TNT in reactor systems that receive a rich carbon source but does affect the rate at which metabolites become tightly bound to the soil. The most rapid transformations and lowest redox potentials were observed in reactors in which an aerobic headspace was maintained suggesting that aerobes play a role in establishing conditions that are most conducive to TNT reduction. PMID- 17273914 TI - Expression of the bacteriophage T4 lysozyme gene in tall fescue confers resistance to gray leaf spot and brown patch diseases. AB - Tall fescue (Festuca arundinacea Schreb.) is an important turf and forage grass species worldwide. Fungal diseases present a major limitation in the maintenance of tall fescue lawns, landscapes, and forage fields. Two severe fungal diseases of tall fescue are brown patch, caused by Rhizoctonia solani, and gray leaf spot, caused by Magnaporthe grisea. These diseases are often major problems of other turfgrass species as well. In efforts to obtain tall fescue plants resistant to these diseases, we introduced the bacteriophage T4 lysozyme gene into tall fescue through Agrobacterium-mediated genetic transformation. In replicated experiments under controlled environments conducive to disease development, 6 of 13 transgenic events showed high resistance to inoculation of a mixture of two M. grisea isolates from tall fescue. Three of these six resistant plants also displayed significant resistance to an R. solani isolate from tall fescue. Thus, we have demonstrated that the bacteriophage T4 lysozyme gene confers resistance to both gray leaf spot and brown patch diseases in transgenic tall fescue plants. The gene may have wide applications in engineered fungal disease resistance in various crops. PMID- 17273915 TI - pORE: a modular binary vector series suited for both monocot and dicot plant transformation. AB - We present a series of 14 binary vectors suitable for Agrobacterium-mediated transformation of dicotyledonous plants and adaptable for biolistic transformation of monocotyledonous plants. The vector size has been minimized by eliminating all non-essential elements from the vector backbone and T-DNA regions while maintaining the ability to replicate independently. The smallest of the vector series is 6.3 kb and possesses an extensive multiple cloning site with 21 unique restriction endonuclease sites that are compatible with common cloning, protein expression, yeast two-hybrid and other binary vectors. The T-DNA region was engineered using a synthetic designer oligonucleotide resulting in an entirely modular system whereby any vector element can be independently exchanged. The high copy number ColE1 origin of replication has been included to enhance plasmid yield in Escherichia coli. FRT recombination sites flank the selectable marker cassette regions and allow for in planta excision by FLP recombinase. The pORE series consists of three basic types; an 'open' set for general plant transformation, a 'reporter' set for promoter analysis and an 'expression' set for constitutive expression of transgenes. The sets comprise various combinations of promoters (P (HPL), P (ENTCUP2) and P (TAPADH)), selectable markers (nptII and pat) and reporter genes (gusA and smgfp). PMID- 17273918 TI - The discriminatory transfer routes of tRNA genes among organellar and nuclear genomes in flowering plants: a genome-wide investigation of indica rice. AB - The transfer and integration of tRNA genes from organellar genomes to the nuclear genome and between organellar genomes occur extensively in flowering plants. The routes of the genetic materials flowing from one genome to another are biased, limited largely by compatibility of DNA replication and repair systems differing among the organelles and nucleus. After thoroughly surveying the tRNA gene transfer among organellar genomes and the nuclear genome of a domesticated rice (Oryza sativa L. ssp. indica), we found that (i) 15 mitochondrial tRNA genes originate from the plastid; (ii) 43 and 80 nuclear tRNA genes are mitochondrion like and plastid-like, respectively; and (iii) 32 nuclear tRNA genes have both mitochondrial and plastid counterparts. Besides the native (or genuine) tRNA gene sets, the nuclear genome contains organelle-like tRNA genes that make up a complete set of tRNA species capable of transferring all amino acids. More than 97% of these organelle-like nuclear tRNA genes flank organelle-like sequences over 20 bp. Nearly 40% of them colocalize with two or more other organelle-like tRNA genes. Twelve of the 15 plastid-like mitochondrial tRNA genes possess 5'- and 3'-flanking sequences over 20 bp, and they are highly similar to their plastid counterparts. Phylogenetic analyses of the migrated tRNA genes and their original copies suggest that intergenomic tRNA gene transfer is an ongoing process with noticeable discriminatory routes among genomes in flowering plants. PMID- 17273919 TI - Population models: stability in one dimension. AB - Some of the simplest models of population growth are one dimensional nonlinear difference equations. While such models can display wild behavior including chaos, the standard biological models have the interesting property that they display global stability if they display local stability. Various researchers have sought a simple explanation for this agreement of local and global stability. Here, we show that enveloping by a linear fractional function is sufficient for global stability. We also show that for seven standard biological models local stability implies enveloping and hence global stability. We derive two methods to demonstrate enveloping and show that these methods can easily be applied to the seven example models. Although enveloping by a linear fractional is a sufficient for global stability, we show by example that such enveloping is not necessary. We extend our results by showing that enveloping implies global stability even when f(x) is a discontinuous multi-function which might be a more reasonable description of real bilogical data. We show that our techniques can be applied to situations which are not population models. Finally, we give examples of population models which have local stability but not global stability. PMID- 17273917 TI - Evolution of the inner light-harvesting antenna protein family of cyanobacteria, algae, and plants. AB - Two hypotheses account for the evolution of the inner antenna light-harvesting proteins of oxygenic photosynthesis in cyanobacteria, algae, and plants: one in which the CP43 protein of photosytem II gave rise to the extrinsic CP43-like antennas of cyanobacteria (i.e. IsiA and Pcb proteins), as a late development, and the other in which CP43 and CP43-like proteins derive from an ancestral protein. In order to determine which of these hypotheses is most likely, we analyzed the family of antenna proteins by a variety of phylogenetic techniques, using alignments of the six common membrane-spanning helices, constructed using information on the antenna proteins' three-dimensional structure, and surveyed for evidence of factors that might confound inference of a correct phylogeny. The first hypothesis was strongly supported. As a consequence, we conclude that the ancestral photosynthetic apparatus, with 11 membrane-spanning helices, split at an early stage during evolution to form, on the one hand, the reaction center of photosystem II and, on the other hand, the ancestor of inner antenna proteins, CP43 (PsbC) and CP47 (PsbB). Only much later in evolution did the CP43 lineage give rise to the CP43' proteins (IsiA and Pcb) of cyanobacteria. PMID- 17273920 TI - Medical applications of digital image morphing. AB - The authors present a unique medical technical application for illustrating the success and/or failure of the physiological healing process as a dynamically morphed video. Two examples used in this report include the healing of a severely fractured humerus from an explosion in Iraq and the other of dramatic tissue destruction from a poisonous spider bite. For the humerus, several sequential x rays obtained throughout orthopedic surgical procedures and the healing process were morphed together representing a time-lapsed video of the healing process. The end result is a video that demonstrates the healing process in an animation that radiologists envision and report to other clinicians. For the brown recluse spider bite, a seemingly benign skin lesion transforms into a wide gaping necrotic wound with dramatic appearance within days. This novel technique is not presented for readily apparent clinical advantage, rather, it may have more immediate application in providing treatment options to referring providers and/or patients, as well as educational value of healing or disease progression over time. Image morphing is one of those innovations that is just starting to come into its own. Morphing is an image processing technology that transforms one image into another by generating a series of intermediate synthetic images. It is the same process that Hollywood uses to turn people into animals in movies, for example. The ability to perform morphing, once restricted to high-end graphics workstations, is now widely available for desktop computers. The authors describe how a series of radiographic images were morphed into a short movie clip using readily available software and an average laptop. The resultant video showed the healing process of an open comminuted humerus fracture that helped demonstrate how amazingly the human body heals in a case presentation in a time-lapse fashion. PMID- 17273921 TI - Efficacy and safety of CyberKnife radiosurgery for acromegaly. AB - OBJECTIVE: Acromegaly is a disease characterized by GH hypersecretion, and is typically caused by a pituitary somatotroph adenoma. The primary mode of therapy is surgery, and radiotherapy is utilized as an adjuvant strategy to treat persistent disease. The aim of this study was to determine the efficacy and tolerability of CyberKnife stereotactic radiosurgery in acromegaly. DESIGN: A retrospective review of biochemical and imaging data for subjects with acromegaly treated with CyberKnife stereotactic radiosurgery between 1998 and 2005 at Stanford University Hospital. PATIENTS: Nine patients with active acromegaly were treated with radiosurgery using the CyberKnife (CK). MEASUREMENTS: Biochemical response based on serum insulin-like growth factor-1 (IGF-1), anterior pituitary hormone function, and tumor size with MRI scans were analyzed. RESULTS: After a mean follow up of 25.4 months (range, 6-53 months), CK radiosurgery resulted in complete biochemical remission in 4 (44.4%) subjects, and in biochemical control with the concomitant use of a somatostatin analog in an additional subject. Smaller tumor size was predictive of treatment success: baseline tumor volume was 1.28 cc (+/- 0.81, SD) vs. 3.93 cc (+/- 1.54) in subjects with a normal IGF-1 vs. those with persistent, active disease, respectively (P = 0.02). The mean biologically effective dose (BED) was higher in subjects who achieved a normal IGF-1 vs. those with persistent, active disease, 172 Gy(3) (+/-28) vs. 94 Gy(3) (+/-17), respectively (P < 0.01). At least one new anterior pituitary hormone deficiency was observed after CK in 3 (33%) patients: two developed hypogonadism, and one developed panhypopituitarism. CONCLUSIONS: CK radiosurgery may be a valuable adjuvant therapy for the management of acromegaly. PMID- 17273922 TI - Lymphocytic panhypophysitis in a young man with involvement of the cavernous sinus and clivus. AB - Lymphocytic hypophysitis is an unusual inflammatory lesion that is caused by autoimmune destruction of the pituitary gland. We report a case of 42-year-old man who presented with a 6-month history of severe headache, blurred vision in the right eye, hearing loss, polyuria, polydipsia, and impotence. Medical history showed that he and his mother had osteopetrosis. The results of the physical examination and laboratory tests showed that secondary hypothyroidism, hypogonadism, and hypocortisolism had developed. Central diabetes insipidus was diagnosed by water deprivation test. MRI of the sella showed pituitary enlargement with symmetrical suprasellar expansion, compression of the chiasma, thickened infundibulum, and involvement of both bilateral cavernous sinuses and clivus. Hormonal substitution with hydrocortisone, levothyroxine, and DDAVP resulted in rapid improvement of all symptoms and signs. Transsphenoidal biopsy was diagnostic of lymphocytic hypophysitis. In spite of extensive literature reviewing, we have not been aware of any case of lymphocytic hypophysitis with clivus involvement. The present case represents a variant of lymphocytic hypophysitis which has progressed to involve bilateral cavernous sinuses and the clivus. PMID- 17273923 TI - Early decision for precut sphincterotomy: is it a risky preference? AB - The aim of this prospective study was to evaluate the results and the complications at a tertiary referral center which frequently uses precutting techniques for biliary cannulation. Four hundred seventy patients with naive papilla for whom biliary intervention was planned were included in the study. If the selective cannulation was not achieved after a few trials, precutting sphincterotomy was performed. The results were evaluated for the frequency, success, and complication rates of precutting. Precutting was performed on 238 (50.6%; 117 male, 121 female; mean age, 58.5 +/- 16.2 years) of 470 patients. Total success rate of endoscopic retrograde cholangiopancreatography (ERCP) was 99.2% (236/238). The rate of complications in patients with versus without precutting was 7 (2.9%) versus 3 (1.3%) for pancreatitis, 2 (0.8%) versus 1 (0.4%) for perforation, and 7 (2.9%) versus 3 (1.3%) for bleeding. The differences between the rates were not significant. Early precutting can be preferable in prolonged cannulation trials of therapeutic ERCP. PMID- 17273924 TI - Effects of combination therapy with direct hemoperfusion using polymyxin B immobilized fiber and oral vancomycin on fulminant pseudomembranous colitis with septic shock. AB - We report 2 cases of fulminant pseudomembranous colitis with septic shock. The first case showed few symptoms, whereas the second case showed recurrence. Both cases rapidly developed shock and blood pressure was uncontrollable except with the use of pressor agents. Direct hemoperfusion using polymyxin B-immobilized fiber, which was previously demonstrated to have excellent therapeutic effects for the treatment of hypotension in septic shock by removing circulating lipopolysaccharide and oral vancomycin dramatically improved both cases' clinical status and decreased their APACHE II scores (from 18 to 8 and from 16 to 9 points, respectively). Therefore, we suggest that direct hemoperfusion using polymyxin B-immobilized fiber improved hypotension-correcting cytokine balance with adsorption of endogenous cannabinoids in serum. Although colectomy is often performed to treat fulminant pseudomembranous colitis with septic shock, direct hemoperfusion can be easily performed with little risk to the patient. These cases strongly indicated that our combination therapy provides an important treatment for fulminant pseudomembranous colitis with septic shock. PMID- 17273925 TI - Shooting gallery operation in the context of establishing a medically supervised injecting center: Sydney, Australia. AB - Shooting galleries (SGs) are illicit off-street spaces close to drug markets used for drug injection. Supervised injecting facilities (SIFs) are low threshold health services where injecting drug users (IDUs) can inject pre-obtained drugs under supervision. This study describes SG use in Kings Cross, Sydney before and after the opening of the Sydney Medically Supervised Injecting Centre (MSIC), Australia's first SIF. Operational and environmental characteristics of SGs, reasons for SG use, and willingness to use MSIC were also examined. An exploratory survey of SG users (n = 31), interviews with SG users (n = 17), and drug workers (n = 8), and counts of used needles routinely collected from SGs (6 months before and after MSIC) and visits to the MSIC (6 months after MSIC) were triangulated. We found five SGs operated during the study period. Key operational characteristics were 24-h operation, AUS $10 entry fee, 30-min time limit, and dual use for sex work. Key reasons for SG use were to avoid police, a preference not to inject in public, and assistance from SG operators in case of overdose. SG users reported high levels of willingness to use the MSIC. The number of used needles collected from SGs decreased by 69% (41,819 vs. 12,935) in the 6 months after MSIC opened, while MSIC visits increased incrementally. We conclude that injections were transferred from SGs to the MSIC, but SGs continued to accommodate injections and harm reduction outreach should be maintained. PMID- 17273926 TI - Exploring associations between physical activity and perceived and objective measures of the built environment. AB - The built environment may be responsible for making nonmotorized transportation inconvenient, resulting in declines in physical activity. However, few studies have assessed both the perceived and objectively measured environment in association with physical activity outcomes. The purpose of this study was to describe the associations between perceptions and objective measures of the built environment and their associations with leisure, walking, and transportation activity. Perception of the environment was assessed from responses to 1,270 telephone surveys conducted in Forsyth County, NC and Jackson, MS from January to July 2003. Participants were asked if high-speed cars, heavy traffic, and lack of crosswalks or sidewalks were problems in their neighborhood or barriers to physical activity. They were also asked if there are places to walk to instead of driving in their neighborhood. Speed, volume, and street connectivity were assessed using Geographic Information Systems (GIS) for both study areas. Locations of crashes were measured using GIS for the NC study area as well. Objective and perceived measures of the built environment were in poor agreement as calculated by kappa coefficients. Few associations were found between any of the physical activity outcomes and perception of speed, volume, or presence of sidewalks as problems in the neighborhood or as barriers to physical activity in regression analyses. Associations between perceptions of having places to walk to and presence of crosswalks differed between study sites. Several associations were found between objective measures of traffic volume, traffic speed, and crashes with leisure, walking, and transportation activity in Forsyth County, NC; however, in Jackson, MS, only traffic volume was associated with any of the physical activity outcomes. When both objective and perceived measures of the built environment were combined into the same model, we observed independent associations with physical activity; thus, we feel that evaluating both objective and perceived measures of the built environment may be necessary when examining the relationship between the built environment and physical activity. PMID- 17273927 TI - Mitochondrial OXPHOS functions in R1H rhabdomyosarcoma and skeletal muscles of the rat. AB - The aim of the study was to determinate mitochondrial oxidative phosphorylation (OXPHOS) functions in rat rhabdomyosarcoma R1H (R1H) and rat skeletal muscles. For that purpose skinned fiber technique and multiple substrate inhibitor titration were adapted to tumor samples. In our animal tumor model (R1H) functional abnormalities of OXPHOS were found compared to skeletal muscles. In R1H the state 3 respiration of pyruvate + malate was decreased: 0.56 +/- 0.28 nmol O(2)/mg/min versus 2.32 +/- 1.19 nmol O(2)/mg/min, P < 0.001, whereas the state 3 respiration of succinate + rotenone was increased: 36 +/- 14% versus 19 +/- 11%, P < 0.001. In R1H the rotenone-insensitive respiration reached higher levels than the antimycin A-insensitive respiration, whereas in normal muscles the converse was observed. Additionally, the obvious difference between the CAT- and the antimycin A-independent respiration indicates an increased part of leak respiration in R1H. By now, the high feasibility of these techniques is appreciated for the investigation of muscles and prospectively for tumors, too. PMID- 17273928 TI - Guanidinoacetate inhibits glutamate uptake in rat striatum of rats at different ages. AB - Glutamate plays a central role in the excitatory synaptic transmission and is important for brain development and functioning. Increased glutamate levels in the synaptic cleft are related to neuronal damage associated with excitotoxicity. Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of guanidinoacetate (GAA) and depletion of creatine. Affected patients present epilepsy and mental retardation whose pathogeny is unclear. In the present study we investigated the in vitro and in vivo (intrastriatal administration) effect of GAA on glutamate uptake by striatum slices of developing and adult rats. Results showed that GAA significantly inhibited in vitro glutamate uptake at 50 microM and 100 microM in all ages tested. We also tested the effect of taurine on the inhibition of glutamate uptake caused by GAA. Taurine significantly attenuated the inhibitory effect caused by 50 microM GAA, but did not alter that provoked by 100 microM GAA. Furthermore, intrastriatal administration of a solution of 30 microM GAA (0.06 nmol/striatum) significantly inhibited glutamate uptake by rat striatum slices. Our results suggest that the inhibition of striatal glutamate uptake caused by GAA might be involved in the neuropathology and especially in the acute neurological features present in patients with GAMT-deficiency. PMID- 17273930 TI - Work-related musculoskeletal disorders in urban bus drivers of Hong Kong. AB - INTRODUCTION: Work-related musculoskeletal disorders (WMSD) affect workers in many occupations including drivers of large vehicles. Urban bus drivers have been found to have high prevalence rates of back problems in overseas studies. Hong Kong is a densely populated city and has a large number of double-deck buses that constitute a major means of public transportation. The present study aimed at investigating the prevalence and characteristics of WMSD in male and female bus drivers who operate double-deck buses in Hong Kong. METHOD: Altogether 481 bus drivers (404 males, 77 females) participated in the study that consisted of a questionnaire survey as well as physical assessment. The questionnaire included questions on work, musculoskeletal complaints and perceived occupational risk factors associated with each discomfort. Physical assessment consisted of measurement of lumbar spine mobility, hand grip strength, sit-and-reach test, and observation of standing and sitting postures. RESULTS: The results showed generally the male drivers had longer years of work experience but their daily workloads were similar to the females. On the average drivers worked 9-10 h per day, with 5 days on and 1 day off. Neck, back, shoulder and knee/thigh areas had the highest 12-month prevalence rates ranging from 35% to 60%, and about 90% of the discomfort was related to bus-driving. Occupational factors of prolonged sitting and anthropometric mismatch were perceived to be most related to musculoskeletal discomfort. On physical examination, grip strength was significantly related to neck and shoulder discomfort. CONCLUSIONS: The present results showed high prevalence rates of WMSD among bus drivers in Hong Kong which warrants further investigation. PMID- 17273931 TI - Vocal features of conversational sarcasm: a comparison of methods. AB - This study investigated vocal cues that differentiate sarcastic utterances from non-sarcastic utterances. Utterances were drawn from videotapes of participant interviews and arranged on a master tape for analysis. Utterances that were identified as sarcastic by speakers and recognized as sarcastic by listeners were randomly arranged with utterances identified and recognized as non-sarcastic by the same participants. Both sarcastic and non-sarcastic utterances were analyzed by two methods-acoustic analysis and perceptual coding. The acoustic analysis proved slightly more successful than the perceptual coding in discriminating between sarcastic and non-sarcastic utterances. The acoustic analysis indicated that fundamental frequency, frequency range, length of utterance, and total amount of sound significantly discriminated sarcastic from non-sarcastic utterances. The perceptual coding method revealed that pitch range, length of utterance, and total amount of sound significantly discriminated sarcastic from non-sarcastic utterances. Moderate correlations were found between the acoustic and perceptual variables. PMID- 17273929 TI - Mapping of QTLs for oral alcohol self-administration in B6.C and B6.I quasi congenic RQI strains. AB - One strategy to identify neurochemical pathways of addiction is to map the relevant genes. In the present study we used 43 B6.C and 35 B6.I inbred RQI mouse strains, carrying <3% donor genome on C57BL/6ByJ background, for gene mapping. The strains were phenotyped for consumption of alcohol (12% v/v) in a two-bottle choice paradigm, and genotyped for 396 microsatellite markers. The current mapping study extends our earlier experiment scanning five mouse chromosomes (Vadasz et al. (2000) Scanning of five chromosomes for alcohol consumption loci. Alcohol 22:25-34) to a whole-genome study, and discusses the differences and limitations. Data were analyzed with composite interval (CIM) and multiple interval (MIM) QTL mapping methods. CIM of B6.C strains detected significant QTLs on chrs. 6 and 12. A suggestive, but not significant, locus was detected in the B6.I strains on chr. 12. The best MIM model for B6.C strains confirmed one QTL on chr. 6 and one QTL on chr. 12, while the MIM model for the B6.I strains confirmed the suggestive locus on chr. 12. Some of the QTLs for alcohol consumption are new, while others confirm previously reported QTLs for alcohol preference, and alcohol acceptance. PMID- 17273932 TI - The influence of language form and conventional wording on judgments of illness. AB - Prior research indicates that category labels influence category judgments, but little is known regarding the effects for familiar categories with significant social consequences. The present studies address this issue by examining the effect of linguistic form on judgments of illnesses. Both mental and physical illnesses were presented in each of three linguistic forms: noun, adjective, and possessive phrase. In Study 1, participants were asked to judge the permanence of a set of novel illnesses that differed in wording (e.g., "He is a baxtermic"; "He is baxtermic"; "He has baxtermia"). In Studies 2 and 3, participants were asked to judge which forms of wording were most familiar for actual mental illnesses (e.g., schizophrenia) and physical illnesses (e.g., diabetes). In Study 4, participants were asked to judge the permanence of a set of familiar illnesses that differed in wording. The results indicated that for novel illnesses, nouns ("is a") imply greatest permanence and possessive nouns ("has") imply least permanence. However, for familiar illnesses, permanence judgments are also influenced by how frequently each form appears in ordinary language use. Mental illnesses are more often expressed with relatively permanent forms ("is" and "is a") , whereas physical illnesses are more often expressed with relatively transient forms ("has"). The results demonstrate the importance of both linguistic form and conventional wording patterns on how categories are interpreted. PMID- 17273934 TI - Brief report: can you see what is not there? low-level auditory-visual integration in autism spectrum disorder. AB - Patients diagnosed with Autism Spectrum Disorder, show impaired integration of information across different senses. The processing-level from which this impairment originates, however, remains unclear. We investigated low-level integration of auditory and visual stimuli in subjects with Autism Spectrum Disorder. High-functioning adult subjects with Autism Spectrum Disorder as well as age- and IQ-matched adults were tested using a task that evokes illusory visual stimuli, by presenting sounds concurrently with visual flashes. In both groups the number of sounds presented significantly affected the number of flashes perceived, yet there was no difference between groups. This finding implicates that any problems arising from integrating auditory and visual information must stem from higher processing stages in high-functioning adults with Autism Spectrum Disorder. PMID- 17273933 TI - Differential diagnosis of Hispanic children referred for autism spectrum disorders: complex issues. AB - This study examines the decision-making process used for differential diagnosis of a sample of Hispanic children referred for autism spectrum disorders (ASDs). Of the sample of 28 children, 18 were diagnosed with ASDs. Of the 10 children who were not diagnosed with ASDs, 80% were found to have multiple diagnostic labels or comorbidities. Mann-Whitney U analyses determined the differences between the children with the most severe social impairment, children with less severe social impairment and the non-autistic children on several domains commonly used to assess ASDs. These analyses indicated significant differences in some characteristics of the children in the sample. Based on these results, a decision tree for the diagnosis of children with and without ASDs with comorbid disorders was developed. PMID- 17273935 TI - Brief report: impaired identification of discrepancies between expressive faces and voices in adults with Asperger's syndrome. AB - The aim of the present experiment was to examine the ability of adults with Asperger's syndrome and age-matched typically-developing controls to identify incongruent and congruent emotional information from the face and voice. In the first part of the experiment, participants determined whether simultaneously presented expressive faces and voices were the same or different. In the second part, participants identified expressive faces and voices in isolation. Results showed that relative to controls, adults with AS were less accurate at distinguishing between congruent and incongruent expressive faces and voices. Both groups obtained similar accuracy to expressive faces and voices presented in isolation. These findings may partially explain some of the difficulties individuals on the autistic spectrum have with social interaction. PMID- 17273936 TI - Stalking, and social and romantic functioning among adolescents and adults with autism spectrum disorder. AB - We examine the nature and predictors of social and romantic functioning in adolescents and adults with ASD. Parental reports were obtained for 25 ASD adolescents and adults (13-36 years), and 38 typical adolescents and adults (13 30 years). The ASD group relied less upon peers and friends for social (OR = 52.16, p < .01) and romantic learning (OR = 38.25, p < .01). Individuals with ASD were more likely to engage in inappropriate courting behaviours (chi2 df = 19 = 3168.74, p < .001) and were more likely to focus their attention upon celebrities, strangers, colleagues, and ex-partners (chi2 df = 5 =2335.40, p < .001), and to pursue their target longer than controls (t = -2.23, df = 18.79, p < .05). These results show that the diagnosis of ASD is pertinent when individuals are prosecuted under stalking legislation in various jurisdictions. PMID- 17273937 TI - Short-term trends in functional limitation and disability among older Asians: a comparison of five Asian settings. AB - The objective of this paper is to examine short-term trends in the prevalence of limitation in Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Nagi physical functioning tasks among persons age 60 years or older in five Asian settings: Indonesia, the Philippines, Singapore, Taiwan and the Beijing Municipality. The data come from recent panel surveys of older adults that span a period of 3-4 years during the mid to late 1990s. Results suggest a general trend toward an increase in functional limitation in four of the five settings, with the most pronounced increases occurring for the Nagi functioning tasks. Compositional differences in the population accounted for little of the increase. The paper discusses the potential implications of these results and places them in the context of past and current trends in functional limitation observed in the United States. PMID- 17273938 TI - A multiscale computational approach to dissect early events in the Erb family receptor mediated activation, differential signaling, and relevance to oncogenic transformations. AB - We describe a hierarchical multiscale computational approach based on molecular dynamics simulations, free energy-based molecular docking simulations, deterministic network-based kinetic modeling, and hybrid discrete/continuum stochastic dynamics protocols to study the dimer-mediated receptor activation characteristics of the Erb family receptors, specifically the epidermal growth factor receptor (EGFR). Through these modeling approaches, we are able to extend the prior modeling of EGF-mediated signal transduction by considering specific EGFR tyrosine kinase (EGFRTK) docking interactions mediated by differential binding and phosphorylation of different C-terminal peptide tyrosines on the RTK tail. By modeling signal flows through branching pathways of the EGFRTK resolved on a molecular basis, we are able to transcribe the effects of molecular alterations in the receptor (e.g., mutant forms of the receptor) to differing kinetic behavior and downstream signaling response. Our molecular dynamics simulations show that the drug sensitizing mutation (L834R) of EGFR stabilizes the active conformation to make the system constitutively active. Docking simulations show preferential characteristics (for wildtype vs. mutant receptors) in inhibitor binding as well as preferential enhancement of phosphorylation of particular substrate tyrosines over others. We find that in comparison to the wildtype system, the L834R mutant RTK preferentially binds the inhibitor erlotinib, as well as preferentially phosphorylates the substrate tyrosine Y1068 but not Y1173. We predict that these molecular level changes result in preferential activation of the Akt signaling pathway in comparison to the Erk signaling pathway for cells with normal EGFR expression. For cells with EGFR over expression, the mutant over activates both Erk and Akt pathways, in comparison to wildtype. These results are consistent with qualitative experimental measurements reported in the literature. We discuss these consequences in light of how the network topology and signaling characteristics of altered (mutant) cell lines are shaped differently in relationship to native cell lines. PMID- 17273939 TI - A novel approach to the detection of synchronisation in EEG based on empirical mode decomposition. AB - Transient neural assemblies mediated by synchrony in particular frequency ranges are thought to underlie cognition. We propose a new approach to their detection, using empirical mode decomposition (EMD), a data-driven approach removing the need for arbitrary bandpass filter cut-offs. Phase locking is sought between modes. We explore the features of EMD, including making a quantitative assessment of its ability to preserve phase content of signals, and proceed to develop a statistical framework with which to assess synchrony episodes. Furthermore, we propose a new approach to ensure signal decomposition using EMD. We adapt the Hilbert spectrum to a time-frequency representation of phase locking and are able to locate synchrony successfully in time and frequency between synthetic signals reminiscent of EEG. We compare our approach, which we call EMD phase locking analysis (EMDPL) with existing methods and show it to offer improved time frequency localisation of synchrony. PMID- 17273940 TI - Using extracellular action potential recordings to constrain compartmental models. AB - We investigate the use of extracellular action potential (EAP) recordings for biophysically faithful compartmental models. We ask whether constraining a model to fit the EAP is superior to matching the intracellular action potential (IAP). In agreement with previous studies, we find that the IAP method under-constrains the parameters. As a result, significantly different sets of parameters can have virtually identical IAP's. In contrast, the EAP method results in a much tighter constraint. We find that the distinguishing characteristics of the waveform--but not its amplitude-resulting from the distribution of active conductances are fairly invariant to changes of electrode position and detailed cellular morphology. Based on these results, we conclude that EAP recordings are an excellent source of data for the purpose of constraining compartmental models. PMID- 17273941 TI - Negotiating a path to efficacy at a clinic of traditional Chinese medicine. AB - Chinese medicine emphasizes the underlying connection of the bodily, emotional, social, and environmental dimensions in illness experience and healing. The therapeutic process, characterized as tiao (attuning, balancing), targets the patient's overall illness condition and experience including both physical and non-physical aspects of suffering. This study, incorporating techniques of microanalysis as an ethnographic tool and using an actual recorded clinical interaction as data, analyzes how the path to effective healing is negotiated among multiple clinical realities at a clinic of Chinese medicine in Beijing. A close examination of interactive features of actual face-to-face communication between a doctor and a patient in a specific case of "stagnation of emotions" reveals that, for an illness recognized in Chinese medicine as originating from disordered emotions, adjustment of the patient's perceptions of reality and social relations is particularly salient in the "attuning" process. Efficacy then should be understood as more than physiological changes produced by herbs, but also as emergent through an interactive event of clinical encounters. This study demonstrates empirically how the clinical process of Chinese medicine works to define and transform the patient's emotions and experience. PMID- 17273942 TI - Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications. AB - The in vitro and in vivo characterization of adult stem cells has allowed researchers to identify certain specific functional features to each tissue specific stem cell. Moreover, recent studies revealed that their malignant counterparts, the cancer progenitor cells with stem cell-like properties, may assume a crucial role for the initiation and progression of locally invasive cancers into disseminated and incurable disease states. Therefore, a new direction in cancer research appears necessary in considering the critical functions of cancer progenitor cells. In this review, we discuss recent concepts on the critical roles of tumorigenic and migrating cancer progenitor cells in carcinogenesis. Particularly, we describe the tumorigenic cascades that are frequently activated through the interplay of diverse hormones, growth factors, cytokines and integrins in cancer progenitor cells versus their further differentiated progeny. The emphasis is on the oncogenic signaling pathways activated during the localized cancer progression and micrometastatic events involved in tumor formation at distant sites such as bone marrow. Of therapeutic interest, important information for the selective molecular targeting of cancer progenitor cells, which must now be considered in developing new effective diagnostic and prognostic methods and curative treatments against the most locally advanced and metastatic cancers, is also described. PMID- 17273944 TI - Do morbidity and mortality conferences still have a role in family medicine residencies? PMID- 17273943 TI - Physiological and pharmacological functions of Mrp2, Mrp3 and Mrp4 as determined from recent studies on gene-disrupted mice. AB - The MRP family is composed of nine transporters, at least eight of which are lipophilic anion transporters that are capable of conferring resistance to various anticancer agents. Recently, mice with gene disruptions in Mrp2, Mrp3 and Mrp4 have been developed. This review will discuss insights into the physiological and pharmacological functions of Mrp2, Mrp3 and Mrp4 afforded by investigations of these new mouse models. PMID- 17273945 TI - Breaking through the glass ceiling. PMID- 17273946 TI - Sweetened canned coffee cessation intervention for subjects with type 2 diabetes mellitus: a preliminary study. PMID- 17273947 TI - Teaching learners to care for children and youth with special health care needs. PMID- 17273948 TI - Smiles for Life: A National Oral Health Curriculum for Family Medicine. A model for curriculum development by STFM groups. AB - The Society of Teachers of Family Medicine Group on Oral Health released Smiles for Life: A National Oral Health Curriculum for Family Medicine in October 2005 to address a need for high-quality residency and medical school curricula in an area of documented physician knowledge deficit. This article describes the background, planning, fund-raising, development, dissemination, and impact of the curriculum. Lessons learned, particularly in the areas of long-distance collaboration, fund-raising, and marketing are reviewed with a goal of serving as a model for future curriculum development efforts. PMID- 17273949 TI - The heart of family medicine. PMID- 17273950 TI - Do you love me: teaching couple dynamics. PMID- 17273951 TI - Major policy changes for primary care: potential lessons for the US New Model of family medicine from the quality and outcomes framework in the United Kingdom. AB - The Future of Family Medicine project in the United States has identified a series of core values and a New Model of practice for family medicine aiming to transform the health and health care of the nation. There are, however, few empirical examples of its effectiveness and acceptability in practice. Recent experiences of changes to primary health care in the United Kingdom (UK), particularly the introduction of the Quality and Outcomes Framework, which rewards practices for delivering evidence-based care, may provide some useful lessons for practitioners and policy makers as they implement aspects of the New Model. In this paper, the authors, who lead the Expert Review of the Quality and Outcomes Framework, critique the five characteristics of the New Model that offer the most relevant learning points for both health care systems and reflect on lessons for both clinicians and policy makers, highlighted by the experience of implementing policy change in the UK. They suggest that incremental implementation, underpinned by robust pilot data and in-depth understanding of the influence of motivation on performance, are key and conclude that sharing issues that have worked well, and less well, are important in helping both countries develop good quality patient care. PMID- 17273952 TI - A residency clinic chronic condition management quality improvement project. AB - BACKGROUND AND OBJECTIVES: Quality improvement in chronic disease management is a major agenda for improving health and reducing health care costs. A six-component chronic disease management model can help guide this effort. Several characteristics of the "new model" of family medicine described by the Future of Family Medicine (FFM) Project Leadership Committee are promulgated to foster practice changes that improve quality. Our objective was to implement and assess a quality improvement project guided by the components of a chronic disease management model and FFM new model characteristics. METHODS: Diabetes was selected as a model chronic disease focus. Multiple practice changes were implemented. A mature electronic medical record facilitated data collection and measurement of quality improvement progress. RESULTS: Data from the diabetes registry demonstrates that our efforts have been effective. Significant improvement occurred in five out of six quality indicators. CONCLUSIONS: Multidisciplinary teamwork in a model residency practice guided by chronic disease management principles and the FFM new model characteristics can produce significant management improvements in one important chronic disease. PMID- 17273954 TI - The future of residency education: implementing a competency-based educational model. AB - Graduate medical programs are faced with increasing calls for competency-based education. All accredited residencies and fellowships must now demonstrate that graduates are competent in six key areas, and outcomes data must be used to improve each program. The transition to competency-based education has challenged programs in all specialties. We describe the design, implementation, and outcomes measurement of a comprehensive, competency-based family medicine curriculum that uses multiple educational components and assessment tools in various settings and relies on both formative and summative feedback. Components include inpatient and outpatient core competencies, a longitudinal didactic curriculum, a competency based procedures curriculum, and use of medical evidence to improve individual patient care in ambulatory practice. In addition to multiple evaluation tools (eg, video monitoring, rotation-specific evaluations, adviser-advisee meetings, faculty meetings, and checklist evaluations of procedures and physical examinations), residents receive feedback from patients, faculty, nurses, transcriptionists, and referring physicians. The curriculum demonstrates resident competence in six core areas and resident confidence in skills acquired by the completion of training. The evaluation system promotes greater objectivity in information provided to future employers and hospitals about residents. This model provides a curricular template for other accredited residency programs. PMID- 17273953 TI - Preceptorship rurality does not affect medical students' shelf exam scores. AB - OBJECTIVE: This study's objective was to determine whether junior medical students' end-of-rotation shelf exam scores varied by the preceptorship county's rurality. METHODS: Student learning during rural preceptorship experiences, 1999 to 2005, was assessed using the students' scores on the National Board of Medical Examiners family medicine subject examination. Rurality was measured using both population density and the rural-urban continuum (RUC) codes. RESULTS: Exam scores were collected between January 1999 and May 2005 for 734 students. Mean scores did not vary significantly by rurality, although they did vary significantly by semester. Test scores of students in rural locations were not statistically significantly different from those of students in urban preceptorships. CONCLUSIONS: Students assigned to preceptorships in rural locations scored at the same levels as students in urban preceptorships. The finding that there were no differences in medical students' exam scores based on the rurality of their family medicine preceptorship site indicates a substantial degree of educational equivalency between urban and rural preceptorships. PMID- 17273955 TI - Physicians' and patients' views of cancer care by family physicians: a report from the American Academy of Family Physicians National Research Network. AB - BACKGROUND AND OBJECTIVES: There has been little research describing the role of family physicians in the care of patients with an active diagnosis of cancer. METHODS: Using qualitative methods, we interviewed 15 family physicians and 15 of their cancer patients. We asked physicians about care of cancer patients in general and of the specific patient included in this study. Patient interviews focused on the role their family physician played in their care and their satisfactions and frustrations with that care. RESULTS: The physicians reported coordinating referrals, providing general medical care, helping with decisions, and providing emotional support. Their involvement was more intense at the time of diagnosis and near death. The patients gave similar responses and also said they valued clear explanations and spending time with and feeling comfortable with their family physicians. CONCLUSIONS: Family physicians fulfill a number of important roles in caring for their patients with an active diagnosis of cancer. More research using representative samples is needed to determine the generalizability of these findings, but this study gives us some preliminary insight into the role family physicians play in cancer care. PMID- 17273956 TI - Eliminating bias in randomized controlled trials: importance of allocation concealment and masking. AB - Randomization in randomized controlled trials involves more than generation of a random sequence by which to assign subjects. For randomization to be successfully implemented, the randomization sequence must be adequately protected (concealed) so that investigators, involved health care providers, and subjects are not aware of the upcoming assignment. The absence of adequate allocation concealment can lead to selection bias, one of the very problems that randomization was supposed to eliminate. Authors of reports of randomized trials should provide enough details on how allocation concealment was achieved so the reader can determine the likelihood of success. Fortunately, a plan of allocation concealment can always be incorporated into the design of a randomized trial. Certain methods minimize the risk of concealment failing more than others. Keeping knowledge of subjects' assignment after allocation from subjects, investigators/health care providers, or those assessing outcomes is referred to as masking (also known as blinding). The goal of masking is to prevent ascertainment bias. In contrast to allocation concealment, masking cannot always be incorporated into a randomized controlled trial. Both allocation concealment and masking add to the elimination of bias in randomized controlled trials. PMID- 17273957 TI - On teamwork. PMID- 17273959 TI - Effectiveness of a continuous quality improvement program on colonoscopy practice. AB - BACKGROUND AND STUDY AIM: Continuous quality improvement (CQI) is recommended by professional societies as part of every colonoscopy program, but little is known with regard to its effectiveness for colonoscopy outcomes. We prospectively assessed whether the implementation of a CQI program in routine clinical practice influences the quality performance of colonoscopy. METHODS: In an open-access endoscopy unit at a secondary care center in Northern Italy, 6-monthly audit cycles were carried out over a 4-year period, to identify reasons for poor colonoscopy outcomes and institute appropriate changes to improve performance. The colonoscopy completion rate and the polyp detection rate as detected by endoscopists were considered to be key measures for improvement. RESULTS: The initial crude colonoscopy completion rate was 84.6%, with a range for individual endoscopists 80.4%-94%. Four endoscopists had a completion rate lower than 90%. The overall polyp detection rate was 34%, with a wide variation among endoscopists (range 14%-42%). Poor patient tolerance and differences in colonoscopist expertise were the main determinants of lack of completion and variation in polyp detection rate. Changes to sedation practice, greater access to endoscopy sessions for the endoscopists with the lowest performance rates, and other organizational arrangements, were implemented to improve quality performance. The crude completion rates improved consistently, up to 93.1%, over the study period. This trend was confirmed even when adjusted completion rates were calculated. All endoscopists reached a crude completion rate of 90% or more and a polyp detection rate of over 20%. The introduction of CQI did not significantly change the overall incidence of procedure-related complications. CONCLUSIONS: The effectiveness of colonoscopy can be improved by implementing a CQI program in routine colonoscopy practice. PMID- 17273960 TI - High-resolution magnification endoscopy can reliably identify normal gastric mucosa, Helicobacter pylori-associated gastritis, and gastric atrophy. AB - BACKGROUND AND STUDY AIMS: The aims of the study were to describe the magnified endoscopic findings in the gastric body, correlate these with histology, and evaluate their reproducibility in the assessment of the magnified endoscopic patterns seen. PATIENTS AND METHODS: A total of 95 consecutive dyspeptic patients underwent upper gastrointestinal endoscopy with a magnifying endoscope. The endoscopists classified the magnified endoscopic patterns and correlated them with the histological findings. In the second part of the study, 200 images were shown to five endoscopists in order to examine inter- and intraobserver variability in image assessment. RESULTS: The magnified endoscopic findings in the gastric body were categorized into four types: type 1, honeycomb-type subepithelial capillary network (SECN) with regular arrangement of collecting venules and regular, round pits; type 2, honeycomb-type SECN with regular, round pits, but loss of collecting venules; type 3, loss of normal SECN and collecting venules, with enlarged white pits surrounded by erythema; and type 4, loss of normal SECN and round pits, with irregular arrangement of collecting venules. The sensitivity, specificity, and positive and negative predictive values of the type 1 pattern for predicting normal gastric mucosa were 92.7% (95% confidence interval [CI] 93.2-97.3%), 100% (95% CI 83.9-100%), 100% (95% CI 92.9-100%), and 83.8% (95% CI 65.5-93.9%). The sensitivity, specificity, and positive and negative predictive values of types 2 and 3 patterns for predicting a Helicobacter pylori-infected stomach were 100% (95% CI 83.9-100%), 92.7% (95% CI 93.2-97.3%), 83.8% (95% CI 65.5-93.9%), and 100% (95% CI 92.9-100%). The sensitivity, specificity, and positive and negative predictive values of a type 4 pattern for predicting gastric atrophy were 90% (95% CI 66.8-98.2%), 96% (95% CI 87.9-98.9%), 85.7% (95% CI 62.6-96.2%), and 97.3% (95% CI 89.6-99.5%. The kappa values for inter- and intraobserver agreement in predicting normal gastric mucosa, H. pylori gastritis, and gastric atrophy were 0.864 and 0.913 respectively. CONCLUSION: High-resolution magnification endoscopy can reliably identify the normal gastric mucosa, H. pylori-associated gastritis, and gastric atrophy in a Western population. PMID- 17273961 TI - Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism. AB - X-linked dystonia-parkinsonism (XDP) is a movement disorder endemic to the Philippines. The disease locus, DYT3, has been mapped to Xq13.1. In a search for the causative gene, we performed genomic sequencing analysis, followed by expression analysis of XDP brain tissues. We found a disease-specific SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion in an intron of the TATA-binding protein associated factor 1 gene (TAF1), which encodes the largest component of the TFIID complex, and significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus. We also identified an abnormal pattern of DNA methylation in the retrotransposon in the genome from the patient's caudate, which could account for decreased expression of TAF1. Our findings suggest that the reduced neuron-specific expression of the TAF1 gene is associated with XDP. PMID- 17273962 TI - Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians. AB - Because mitochondria play pivotal roles in both insulin secretion from the pancreatic beta cells and insulin resistance of skeletal muscles, we performed a large-scale association study to identify mitochondrial haplogroups that may confer resistance against or susceptibility to type 2 diabetes mellitus (T2DM). The study population comprised 2,906 unrelated Japanese individuals, including 1,289 patients with T2DM and 1,617 controls, and 1,365 unrelated Korean individuals, including 732 patients with T2DM and 633 controls. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups (i.e., F, B, A, N9a, M7a, M7b, G, D4a, D4b, and D5). Multivariate logistic-regression analysis with adjustment for age and sex revealed that the mitochondrial haplogroup N9a was significantly associated with resistance against T2DM (P=.0002) with an odds ratio of 0.55 (95% confidence interval 0.40-0.75). Even in the modern environment, which is often characterized by satiety and physical inactivity, this haplogroup might confer resistance against T2DM. PMID- 17273963 TI - Seemingly neutral polymorphic variants may confer immunity to splicing inactivating mutations: a synonymous SNP in exon 5 of MCAD protects from deleterious mutations in a flanking exonic splicing enhancer. AB - The idea that point mutations in exons may affect splicing is intriguing and adds an additional layer of complexity when evaluating their possible effects. Even in the best-studied examples, the molecular mechanisms are not fully understood. Here, we use patient cells, model minigenes, and in vitro assays to show that a missense mutation in exon 5 of the medium-chain acyl-CoA dehydrogenase (MCAD) gene primarily causes exon skipping by inactivating a crucial exonic splicing enhancer (ESE), thus leading to loss of a functional protein and to MCAD deficiency. This ESE functions by antagonizing a juxtaposed exonic splicing silencer (ESS) and is necessary to define a suboptimal 3' splice site. Remarkably, a synonymous polymorphic variation in MCAD exon 5 inactivates the ESS, and, although this has no effect on splicing by itself, it makes splicing immune to deleterious mutations in the ESE. Furthermore, the region of MCAD exon 5 that harbors these elements is nearly identical to the exon 7 region of the survival of motor neuron (SMN) genes that contains the deleterious silent mutation in SMN2, indicating a very similar and finely tuned interplay between regulatory elements in these two genes. Our findings illustrate a mechanism for dramatic context-dependent effects of single-nucleotide polymorphisms on gene expression regulation and show that it is essential that potential deleterious effects of mutations on splicing be evaluated in the context of the relevant haplotype. PMID- 17273964 TI - A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy. AB - The following study describes the discovery of a new inherited metabolic disorder, dolichol kinase (DK1) deficiency. DK1 is responsible for the final step of the de novo biosynthesis of dolichol phosphate. Dolichol phosphate is involved in several glycosylation reactions, such as N-glycosylation, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and C- and O mannosylation. We identified four patients who were homozygous for one of two mutations (c.295T-->A [99Cys-->Ser] or c.1322A-->C [441Tyr-->Ser]) in the corresponding hDK1 gene. The residual activity of mutant DK1 was 2%-4% when compared with control cells. The mutated alleles failed to complement the temperature-sensitive phenotype of DK1-deficient yeast cells, whereas the wild type allele restored the normal growth phenotype. Affected patients present with a very severe clinical phenotype, with death in early infancy. Two of the patients died from dilative cardiomyopathy. PMID- 17273965 TI - Evidence of positive selection on a class I ADH locus. AB - The alcohol dehydrogenase (ADH) family of enzymes catalyzes the reversible oxidation of alcohol to acetaldehyde. Seven ADH genes exist in a segment of ~370 kb on 4q21. Products of the three class I ADH genes that share 95% sequence identity are believed to play the major role in the first step of ethanol metabolism. Because the common belief that selection has operated at the ADH1B*47His allele in East Asian populations lacks direct biological or statistical evidence, we used genomic data to test the hypothesis. Data consisted of 54 single-nucleotide polymorphisms (SNPs) across the ADH clusters in a global sampling of 42 populations. Both the F(st) statistic and the long-range haplotype (LRH) test provided positive evidence of selection in several East Asian populations. The ADH1B Arg47His functional polymorphism has the highest F(st) of the 54 SNPs in the ADH cluster, and it is significantly above the mean F(st) of 382 presumably neutral sites tested on the same 42 population samples. The LRH test that uses cores including that site and extending on both sides also gives significant evidence of positive selection in some East Asian populations for a specific haplotype carrying the ADH1B*47His allele. Interestingly, this haplotype is present at a high frequency in only some East Asian populations, whereas the specific allele also exists in other East Asian populations and in the Near East and Europe but does not show evidence of selection with use of the LRH test. Although the ADH1B*47His allele conveys a well-confirmed protection against alcoholism, that modern phenotypic manifestation does not easily translate into a positive selective force, and the nature of that selective force, in the past and/or currently, remains speculative. PMID- 17273966 TI - First reported patient with human ERCC1 deficiency has cerebro-oculo-facio skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure. AB - Nucleotide excision repair (NER) is a genome caretaker mechanism responsible for removing helix-distorting DNA lesions, most notably ultraviolet photodimers. Inherited defects in NER result in profound photosensitivity and the cancer-prone syndrome xeroderma pigmentosum (XP) or two progeroid syndromes: Cockayne and trichothiodystrophy syndromes. The heterodimer ERCC1-XPF is one of two endonucleases required for NER. Mutations in XPF are associated with mild XP and rarely with progeria. Mutations in ERCC1 have not been reported. Here, we describe the first case of human inherited ERCC1 deficiency. Patient cells showed moderate hypersensitivity to ultraviolet rays and mitomycin C, yet the clinical features were very severe and, unexpectedly, were compatible with a diagnosis of cerebro-oculo-facio-skeletal syndrome. This discovery represents a novel complementation group of patients with defective NER. Further, the clinical severity, coupled with a relatively mild repair defect, suggests novel functions for ERCC1. PMID- 17273967 TI - Autosomal recessive ichthyosis with hypotrichosis caused by a mutation in ST14, encoding type II transmembrane serine protease matriptase. AB - In this article, we describe a novel autosomal recessive ichthyosis with hypotrichosis syndrome, characterized by congenital ichthyosis associated with abnormal hair. Using homozygosity mapping, we mapped the disease locus to 11q24.3 q25. We screened the ST14 gene, which encodes matriptase, since transplantation of skin from matriptase(-/-)-knockout mice onto adult athymic nude mice has been shown elsewhere to result in an ichthyosislike phenotype associated with almost complete absence of erupted pelage hairs. Mutation analysis revealed a missense mutation, G827R, in the highly conserved peptidase S1-S6 domain. Marked skin hyperkeratosis due to impaired degradation of the stratum corneum corneodesmosomes was observed in the affected individuals, which suggests that matriptase plays a significant role in epidermal desquamation. PMID- 17273968 TI - Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. AB - The mitochondrial phosphate carrier SLC25A3 transports inorganic phosphate into the mitochondrial matrix, which is essential for the aerobic synthesis of adenosine triphosphate (ATP). We identified a homozygous mutation--c.215G-->A (p.Gly72Glu)--in the alternatively spliced exon 3A of this enzyme in two siblings with lactic acidosis, hypertrophic cardiomyopathy, and muscular hypotonia who died within the 1st year of life. Functional investigation of intact mitochondria showed a deficiency of ATP synthesis in muscle but not in fibroblasts, which correlated with the tissue-specific expression of exon 3A in muscle versus exon 3B in fibroblasts. The enzyme defect was confirmed by complementation analysis in yeast. This is the first report of patients with mitochondrial phosphate-carrier deficiency. PMID- 17273969 TI - Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. AB - Mutations in the cohesin regulators NIPBL and ESCO2 are causative of the Cornelia de Lange syndrome (CdLS) and Roberts or SC phocomelia syndrome, respectively. Recently, mutations in the cohesin complex structural component SMC1A have been identified in two probands with features of CdLS. Here, we report the identification of a mutation in the gene encoding the complementary subunit of the cohesin heterodimer, SMC3, and 14 additional SMC1A mutations. All mutations are predicted to retain an open reading frame, and no truncating mutations were identified. Structural analysis of the mutant SMC3 and SMC1A proteins indicate that all are likely to produce functional cohesin complexes, but we posit that they may alter their chromosome binding dynamics. Our data indicate that SMC3 and SMC1A mutations (1) contribute to approximately 5% of cases of CdLS, (2) result in a consistently mild phenotype with absence of major structural anomalies typically associated with CdLS, and (3) in some instances, result in a phenotype that approaches that of apparently nonsyndromic mental retardation. PMID- 17273970 TI - The Evolution of satellite III DNA subfamilies among primates. AB - We demonstrate that satellite III (SatIII) DNA subfamilies cloned from human acrocentric chromosomes arose in the Hominoidea superfamily. Two groups, distinguished by sequence composition, evolved nonconcurrently, with group 2 evolving 16-23 million years ago (MYA) and the more recent group 1 sequences emerging approximately 4.5 MYA. We also show the relative order of emergence of each group 2 subfamily in the various primate species. Our results show that each SatIII subfamily is an independent evolutionary unit, that the rate of evolution is not uniform between species, and that the evolution within a species is not uniform between chromosomes. PMID- 17273971 TI - Gene-expression variation within and among human populations. AB - Understanding patterns of gene-expression variation within and among human populations will provide important insights into the molecular basis of phenotypic diversity and the interpretation of patterns of expression variation in disease. However, little is known about how gene-expression variation is apportioned within and among human populations. Here, we characterize patterns of natural gene-expression variation in 16 individuals of European and African ancestry. We find extensive variation in gene-expression levels and estimate that approximately 83% of genes are differentially expressed among individuals and that approximately 17% of genes are differentially expressed among populations. By decomposing total gene-expression variation into within- versus among population components, we find that most expression variation is due to variation among individuals rather than among populations, which parallels observations of extant patterns of human genetic variation. Finally, we performed allele-specific quantitative polymerase chain reaction to demonstrate that cis-regulatory variation in the lymphocyte adaptor protein (SH2B adapter protein 3) contributes to differential expression between European and African samples. These results provide the first insight into how human population structure manifests itself in gene-expression levels and will help guide the search for regulatory quantitative trait loci. PMID- 17273972 TI - Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions. AB - Deletion 22q11.2 syndrome is the most frequent known microdeletion syndrome and is associated with a highly variable phenotype, including DiGeorge and Shprintzen (velocardiofacial) syndromes. Although haploinsufficiency of the T-box transcription factor gene TBX1 is thought to cause the phenotype, to date, only four different point mutations in TBX1 have been reported in association with six of the major features of 22q11.2 deletion syndrome. Although, for the two truncating mutations, loss of function was previously shown, the pathomechanism of the missense mutations remains unknown. We report a novel heterozygous missense mutation, H194Q, in a familial case of Shprintzen syndrome and show that this and the two previously reported missense mutations result in gain of function, possibly through stabilization of the protein dimer DNA complex. We therefore conclude that TBX1 gain-of-function mutations can result in the same phenotypic spectrum as haploinsufficiency caused by loss-of-function mutations or deletions. PMID- 17273973 TI - Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike. AB - Craniofacial abnormality is one of the major clinical manifestations of Smith Magenis syndrome (SMS). Previous analyses in a mixed genetic background of several SMS mouse models--including Df(11)17/+ and Df(11)17-1/+, which have 2-Mb and 590-kb deletions, respectively, and Rai1(-/+)--revealed that the penetrance of the craniofacial phenotype appears to be influenced by deletion size and genetic background. We generated an additional strain with a 1-Mb deletion intermediate in size between the two described above. Remarkably, the penetrance of its craniofacial anomalies in the mixed background was between those of Df(11)17 and Df(11)17-1. We further analyzed the deletion mutations and the Rai1( /+) allele in a pure C57BL/6 background, to control for nonlinked modifier loci. The penetrance of the craniofacial anomalies was markedly increased for all the strains in comparison with the mixed background. Mice with Df(11)17 and Df(11)17 1 deletions had a similar penetrance, suggesting that penetrance may be less influenced by deletion size, whereas that of Rai1(-/+) mice was significantly lower than that of the deletion strains. We hypothesize that potential trans regulatory sequence(s) or gene(s) that reside within the 590-kb genomic interval surrounding Rai1 are the major modifying genetic element(s) affecting the craniofacial penetrance. Moreover, we confirmed the influence of genetic background and different deletion sizes on the phenotype. The complicated control of the penetrance for one phenotype in SMS mouse models provides tools to elucidate molecular mechanisms for penetrance and clearly shows that a null allele caused by chromosomal deletion can have different phenotypic consequences than one caused by gene inactivation. PMID- 17273974 TI - Polymorphic variation in human meiotic recombination. AB - In this study, our phenotype of interest is meiotic recombination. Using genotypes of approximately 6,000 SNP markers in members of the Centre d'Etude du Polymorphisme Humain Utah pedigrees, we found extensive individual variation in the number of female and male recombination events. The locations and frequencies of these recombination events vary along the genome. In both female and male meiosis, the regions with the most recombination events are found at the ends of the chromosomes. Our analysis also shows that there are polymorphic differences among individuals in the activity of the recombination "jungles"; these preferred sites of meiotic recombination differ greatly among individuals. These findings have important implications for understanding genetic disorders that result from improper chromosome segregation. PMID- 17273975 TI - No gene is an island: the flip-flop phenomenon. AB - An increasing number of publications are replicating a previously reported disease-marker association but with the risk allele reversed from the previous report. Do such "flip-flop" associations confirm or refute the previous association findings? We hypothesized that these associations may indeed be confirmations but that multilocus effects and variation in interlocus correlations contribute to this flip-flop phenomenon. We used theoretical modeling to demonstrate that flip-flop associations can occur when the investigated variant is correlated, through interactive effects or linkage disequilibrium, with a causal variant at another locus, and we show how these findings could explain previous reports of flip-flop associations. PMID- 17273976 TI - Localization of a gene for nonsyndromic renal hypodysplasia to chromosome 1p32 33. AB - Nonsyndromic defects in the urinary tract are the most common cause of end-stage renal failure in children and account for a significant proportion of adult nephropathy. The genetic basis of these disorders is not fully understood. We studied seven multiplex kindreds ascertained via an index case with a nonsyndromic solitary kidney or renal hypodysplasia. Systematic ultrasonographic screening revealed that many family members harbor malformations, such as solitary kidneys, hypodysplasia, or ureteric abnormalities (in a total of 29 affected individuals). A genomewide scan identified significant linkage to a 6.9 Mb segment on chromosome 1p32-33 under an autosomal dominant model with reduced penetrance (peak LOD score 3.5 at D1S2652 in the largest kindred). Altogether, three of the seven families showed positive LOD scores at this interval, demonstrating heterogeneity of the trait (peak HLOD 3.9, with 45% of families linked). The chromosome 1p32-33 interval contains 52 transcription units, and at least 23 of these are expressed at stage E12.5 in the murine ureteric bud and/or metanephric mesenchyme. These data show that autosomal dominant nonsyndromic renal hypodysplasia and associated urinary tract malformations are genetically heterogeneous and identify a locus for this common cause of human kidney failure. PMID- 17273978 TI - Mutation in CUL4B, which encodes a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation. AB - We reevaluated a previously reported family with an X-linked mental retardation syndrome and attempted to identify the underlying genetic defect. Screening of candidate genes in a 10-Mb region on Xq25 implicated CUL4B as the causative gene. CUL4B encodes a scaffold protein that organizes a cullin-RING (really interesting new gene) ubiquitin ligase (E3) complex in ubiquitylation. A base substitution, c.1564C-->T, converted a codon for arginine into a premature termination codon, p.R388X, and rendered the truncated peptide completely devoid of the C-terminal catalytic domain. The nonsense mutation also results in nonsense-mediated mRNA decay in patients. In peripheral leukocytes of obligate carriers, a strong selection against cells expressing the mutant allele results in an extremely skewed X-chromosome inactivation pattern. Our findings point to the functional significance of CUL4B in cognition and in other aspects of human development. PMID- 17273977 TI - Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. AB - We observed two unrelated consanguineous families with malformation syndromes sharing anophthalmia and distinct eyebrows as common signs, but differing for alveolar capillary dysplasia or complex congenital heart defect in one and diaphragmatic hernia in the other family. Homozygosity mapping revealed linkage to a common locus on chromosome 15, and pathogenic homozygous mutations were identified in STRA6, a member of a large group of "stimulated by retinoic acid" genes encoding novel transmembrane proteins, transcription factors, and secreted signaling molecules or proteins of largely unknown function. Subsequently, homozygous STRA6 mutations were also demonstrated in 3 of 13 patients chosen on the basis of significant phenotypic overlap to the original cases. While a homozygous deletion generating a premature stop codon (p.G50AfsX22) led to absence of the immunoreactive protein in patient's fibroblast culture, structural analysis of three missense mutations (P90L, P293L, and T321P) suggested significant effects on the geometry of the loops connecting the transmembrane helices of STRA6. Two further variations in the C-terminus (T644M and R655C) alter specific functional sites, an SH2-binding motif and a phosphorylation site, respectively. STRA6 mutations thus define a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the "STRA" group. PMID- 17273979 TI - Efficient association mapping of quantitative trait loci with selective genotyping. AB - Selective genotyping (i.e., genotyping only those individuals with extreme phenotypes) can greatly improve the power to detect and map quantitative trait loci in genetic association studies. Because selection depends on the phenotype, the resulting data cannot be properly analyzed by standard statistical methods. We provide appropriate likelihoods for assessing the effects of genotypes and haplotypes on quantitative traits under selective-genotyping designs. We demonstrate that the likelihood-based methods are highly effective in identifying causal variants and are substantially more powerful than existing methods. PMID- 17273980 TI - Antler size provides an honest signal of male phenotypic quality in roe deer. AB - Identifying factors shaping secondary sexual traits is essential in understanding how their variation may influence male fitness. Little information is available on the allocation of resources to antler growth in territorial ungulates with low sexual size dimorphism. We investigated phenotypic and environmental factors affecting both absolute and relative antler size of male roe deer in three contrasting populations in France and Sweden. In the three populations, we found marked age-specific variation in antler size, with an increase in both absolute and relative antler size between yearling and prime-age stages, followed by a decrease (senescence) for males older than 7 years. Antler size increased allometrically with body mass. This increase was particularly strong for senescent males, suggesting the evolution of two reproductive tactics: heavy old males invested particularly heavily in antler growth (potentially remaining competitive for territories), whereas light old males grew small antlers (potentially abandoning territory defense). Finally, environmental conditions had little effect on antler size: only population density negatively affected absolute antler size in one of the three populations. Antler size may therefore provide an honest signal of male phenotypic quality in roe deer. We discuss the implications of these results in terms of territory tenure and mating competition. PMID- 17273981 TI - A coevolutionary arms race causes ecological speciation in crossbills. AB - We examined three ecological factors potentially causing premating reproductive isolation to determine whether divergent selection as a result of coevolution between South Hills crossbills (Loxia curvirostra complex) and Rocky Mountain lodgepole pine (Pinus contorta latifolia) promotes ecological speciation. One factor was habitat isolation arising because of enhanced seed defenses of lodgepole pine in the South Hills. This caused the crossbill call types (morphologically and vocally differentiated forms) adapted to alternative resources to be rare. Another occurred when crossbills of other call types moved into the South Hills late in the breeding season and feeding conditions were deteriorating so that relatively few non-South Hills crossbills bred ("immigrant infecundity"). Finally, among those crossbills that bred, pairing was strongly assortative by call type (behavioral isolation). Total reproductive isolation between South Hills crossbills and the two other crossbills most common in the South Hills (call types 2 and 5) summed to .9975 and .9998, respectively, on a scale of 0 (no reproductive isolation) to 1 (complete reproductive isolation). These extremely high levels of reproductive isolation indicate that the divergent selection resulting from the coevolutionary arms race between crossbills and lodgepole pine is causing the South Hills crossbill to speciate. PMID- 17273982 TI - Antinociceptive and antiinflammatory activities of pine (Pinus densiflora) pollen extract. AB - The study aimed to evaluate the antinociceptive and antiinflammatory activity of pine (Pinus densiflora) pollen in mice. The antinociceptive activity was determined using acetic acid-induced abdominal constriction and formalin-induced licking, and the hot plate test. Antiinflammatory effects were evaluated using carrageenan- and formalin-induced paw edema, and arachidonic acid-induced ear edema in mice. The ethanol extract of pine pollen (100 and 200 mg/kg, p.o.) produced a significant inhibition of both phases of the formalin pain test in mice, a reduction in mouse writhing induced by acetic acid and an elevation of the pain threshold in the hot plate test in mice. The pine pollen extract also produced a significant inhibition of carrageenan- and formalin-induced paw edema as well as arachidonic acid-induced ear edema in mice. The inhibitions were similar to those produced by aminopyrine and indomethacin, p.o. The different polyphenols found in pine pollen could account for the antinociceptive and antiinflammatory actions. The results obtained indicate that the extract possesses analgesic and antiinflammatory effects. PMID- 17273983 TI - Evaluation of the growth inhibitory activities of Triphala against common bacterial isolates from HIV infected patients. AB - The isolation of microbial agents less susceptible to regular antibiotics and the rising trend in the recovery rates of resistant bacteria highlights the need for newer alternative principles. Triphala has been used in traditional medicine practice against certain diseases such as jaundice, fever, cough, eye diseases etc. In the present study phytochemical (phenolic, flavonoid and carotenoid) and antibacterial activities of aqueous and ethanol extracts of Triphala and its individual components (Terminalia chebula, Terminalia belerica and Emblica officinalis) were tested against certain bacterial isolates (Pseudomonas aeruginosa, Klebsiella pneumoniae, Shigella sonnei, S. flexneri, Staphylococcus aureus, Vibrio cholerae, Salmonella paratyphi-B, Escherichia coli, Enterococcus faecalis, Salmonella typhi) obtained from HIV infected patients using Kirby Bauer's disk diffusion and minimum inhibitory concentration (MIC) methods. T. chebula was found to possess high phytochemical content followed by T. belerica and E. officinalis in both aqueous and ethanol extracts. Further, most of the bacterial isolates were inhibited by the ethanol and aqueous extracts of T. chebula followed by T. belerica and E. officinalis by both disk diffusion and MIC methods. The present study revealed that both individual and combined aqueous and ethanol extracts of Triphala have antibacterial activity against the bacterial isolates tested. PMID- 17273984 TI - Wen-pi-tang-Hab-Wu-ling-san, an oriental herbal prescription, attenuates epithelial-mesenchymal transdifferentiation stimulated by TGF-beta1 in kidney cells. AB - Wen-pi-tang-Hab-Wu-ling-san (WHW), an oriental herbal prescription, is currently used in oriental clinics for the treatment of chronic renal failure (CRF). While its effectiveness has been supported by a series of modern studies, the underlying mechanism remains poorly understood. CRF progression involves tubulointerstitial fibrosis where transforming growth factor-beta1 (TGF-beta1) plays a critical role by inducing epithelial-mesenchymal transdifferentiation (EMT). This study examined whether WHW extract attenuated the TGF-beta1-induced EMT in Madin-Darby canine kidney cells. When the cells were stimulated by TGF beta1 (2.5 ng/mL), they exhibited an elongated, spindle-shaped appearance but this morphological change was significantly suppressed by WHW extract (1 mg/mL). The WHW extract did not show notable cytotoxicity and even mitigated the cytotoxic effects of TGF-beta1. It inhibited the expression of alpha-smooth muscle actin (alpha-SMA), a marker of EMT, but not the secretion of matrix metalloproteinases stimulated by TGF-beta1. The WHW extract also inhibited the phosphorylation of Smad2 that mediates TGF-beta1 signaling leading to alpha-SMA expression. The present study suggests that WHW extract may provide renal protective effects through modulation of the TGF-beta1/Smad2/alpha-SMA pathway involved in fibrosis. PMID- 17273985 TI - When a parent has cancer: a community based program for school personnel. AB - Little information has been published on interventions designed to help school personnel respond to challenges faced by a family dealing with parental cancer. The current study describes the development and piloting of a program that educated school professionals about cancer's impact on families, and effective ways of supporting families facing parental cancer. The program was implemented at four sites; 244 participants completed self-report questionnaires before and after the program assessing knowledge and anxiety about helping families. t-tests indicated that after the program, participants rated themselves as significantly more knowledgeable and confident about helping families with parental cancer. These differences represented large effect sizes. Post hoc comparisons revealed that initial knowledge and knowledge change varied by profession, having had personal experience with cancer, and having worked with several families facing cancer. Participants reported learning about how to reach out and listen to families' needs. These results are extremely encouraging; plans for further program refinements and evaluation are discussed. PMID- 17273988 TI - Parental cancer and dependent children: selected issues for future research. PMID- 17273987 TI - The psychosocial impact of parental cancer on children and adolescents: a systematic review. AB - This review aimed to identify (i) whether early stage parental cancer is associated with an increased risk of psychosocial difficulties amongst children and adolescents; (ii) which factors are associated with variations in psychosocial functioning amongst these children and adolescents. Searches of four electronic databases and the reference lists of relevant articles revealed 10 studies which satisfied the inclusion criteria for the first review question and thirteen studies for the second. Limitations in methodological quality and modest numbers of studies examining the same variables, restricted the conclusions which could be drawn. Overall, the evidence suggests that children and adolescents do not generally experience elevated levels of serious psychosocial difficulties compared to reference groups, but they are at a slightly increased risk for internalising type problems. Adolescent daughters appear to be the most negatively affected group. The prevalent use of measures of child psychopathology may be masking more context-specific problems and lower levels of distress. Family variables, especially family communication/expressiveness, are consistently associated with child/adolescent psychosocial functioning and there is suggestive evidence for the role of maternal depression/adjustment and parenting variables. There is little evidence that medical/treatment variables are important predictors of child outcomes. These findings have implications for identifying families with children most in need of support and indicating variables to target in interventions. PMID- 17273989 TI - Surfactant protein-A mRNA expression by human fetal membranes is increased in histological chorioamnionitis but not in spontaneous labour at term. AB - Surfactant protein-A (SP-A) is produced by the fetal lung, participates in innate immunity, and has been proposed to play a role in the initiation of parturition in mice. Amniotic fluid SP-A concentration increases as a function of gestational age, and SP-A protein has been demonstrated in human chorioamniotic membranes. This study was conducted to determine whether parturition at term, gestational age and chorioamnionitis in preterm delivery (PTD) are associated with changes in the expression of SP-A in the chorioamniotic membranes. Chorioamniotic membranes were obtained from women at term and women with PTD (n=58). SP-A mRNA and protein expression was detected in amniotic epithelial cells, chorionic trophoblasts and macrophages by in situ hybridization and immunohistochemistry. Quantitative real time reverse transcription-PCR demonstrated predominant expression of SP-A1 mRNA, whose expression was 17.4-fold higher in patients with PTD with chorioamnionitis (n=15) than in those without (n=13) (p=0.018). While no difference was observed in SP-A1 mRNA expression in the chorioamniotic membranes of women at term not in labour (n=16) and those in labour (n=14) (p=0.87), the expression in term membranes was higher than that of membranes from women with PTD without chorioamnionitis (p=0.003). Analysis of JAR choriocarcinoma cells demonstrated SP A1 mRNA expression that was up-regulated following lipopolysaccharide treatment. Furthermore, monocytic cell lines (THP-1 and U937) and peripheral blood monocytes (CD14+/CD115+) obtained from pregnant women also expressed SP-A1 mRNA and protein, suggesting the presence of autocrine/paracrine activation in vivo. Interestingly, a mid-trimester amniotic fluid sample obtained from a case of tracheal atresia contained SP-A (3.13 microg/ml), indicating the presence of SP-A of extrapulmonary origin. These findings suggest not only that SP-A expression is a part of the innate immune response deployed during chorioamniotic inflammation, but also that chorioamniotic membranes are a source of SP-A in the amniotic fluid with advancing gestation. PMID- 17273990 TI - Immunoregulatory role of Jalpha281 T cells in aged mice developing lupus-like nephritis. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Valpha14 Jalpha281 chains paired with some Vbeta domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jalpha281 knockout (KO) mice produce anti dsDNA. Here we show that old Jalpha281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jalpha281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jalpha281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jalpha281+ cells, probably associated with the activation of marginal zone B cells. PMID- 17273991 TI - Increased natural cytotoxicity receptor expression and relevant IL-10 production in NK cells from chronically infected viremic HCV patients. AB - Hepatitis C virus (HCV) readily establishes high-level lifelong persistent infection in the majority of immunocompetent adults with failure of HCV-specific CD8+ CTL to clear viral replication. Virus-induced conditioning of innate immune responses is a possible mechanism that may contribute to the impairment of virus specific CD8+ CTL responses. Here, we analyzed whether triggering of NK cell receptor expression and function is affected during chronic viremic HCV infection. Flow cytometric analysis of purified resting peripheral NK cells showed no evidence of NK cell activation, while analysis of natural cytotoxicity receptors (NCR) showed that NK cells from HCV-infected patients had selective increased expression of NKp30 and NKp46. NK cells had corresponding conserved cytotoxic activity against all targets with the exception of HepG2 hepatoma cells. Freshly separated NK cells from HCV patients showed significant production of IL-10 and normal concentrations of IFN-gamma upon cell-mediated triggering. Thus, increased expression of NKp30 during HCV infection with increased IL-10 production could contribute, once NK cells localize in the liver, to a NK-DC crosstalk leading to skewing of subsequent adaptive immune responses and lack of virus control. PMID- 17273992 TI - Functional and biophysical characterization of an HLA-A*6801-restricted HIV specific T cell receptor. AB - HLA-A*6801 exhibits several unusual features. First, it is known to bind weakly to CD8 due to the presence of an A245V substitution in the alpha3 domain. Second, it is able to accommodate unusually long peptides as a result of peptide 'kinking' in the binding groove. Third, CD8+ cytotoxic T lymphocytes that recognise HLA-A*6801-restricted antigens can tolerate substantial changes in the peptide sequence without apparent loss of recognition. In addition, it has been suggested that HLA-A68-restricted TCR might bind with higher affinity than other TCR due to their selection in the presence of a decreased contribution from CD8. Here we (1) examine monoclonal T cell recognition of an HLA-A*6801-restricted HIV 1 Tat-derived 11-amino acid peptide (ITKGLGISYGR) and natural variant sequences thereof; (2) measure the affinity and kinetics of a TCR/pHLA-A68 interaction biophysically for the first time, showing that equilibrium binding occurs within the range previously determined for non-HLA-A68-restricted TCR (KD approx. 7 microM); and (3) show that "normalization" of the non-canonical HLA-A*6801 CD8 binding domain enhances recognition of agonist peptides without inducing non specific activation. This latter effect may provide a fundamental new mechanism with which to enhance T cell immunity to specific antigens. PMID- 17273995 TI - Imaging the immunological synapse. PMID- 17273996 TI - Immunoregulatory and antimicrobial activities of myeloid cells. AB - 180 scientists recently met at the 20th Annual meeting of the European Macrophage and Dendritic Cell Society to discuss the interaction between interferons, myeloid cells, TLR, killing mechanisms and microbial pathogens. PMID- 17273993 TI - Beta-selection: abundance of TCRbeta-/gammadelta- CD44- CD25- (DN4) cells in the foetal thymus. AB - Expression of TCRbeta and pre-TCR signalling are essential for differentiation of CD4- CD8- double negative (DN) thymocytes to the CD4+ CD8+ double-positive (DP) stage. Thymocyte development in adult Rag1, Rag2 or TCRbetadelta-deficient mice is arrested at the DN3 stage leading to the assumption that pre-TCR signalling and beta-selection occur at, and are obligatory for, the transition from DN3 to DN4. We show that the majority of DN3 and DN4 cells that differentiate during early embryogenesis in wild-type mice do not express intracellular (ic) TCRbeta/gammadelta. These foetal icTCRbeta-/gammadelta- DN4 cells were T lineage as determined by expression of Thy1 and icCD3 and TCRbeta DJ rearrangement. In addition, in the foetal Rag1-/- thymus, a normal percentage of DN4 cells were present. In wild-type mice after hydrocortisone-induced synchronisation of differentiation, the majority of DN4 cells that first emerged did not express icTCRbeta/gammadelta, showing that adult thymocytes can also differentiate to the DN4 stage independently of pre-TCR signalling. Pre-TCR signalling induced expansion in the DN4 population, but lack of TCRbeta/gammadelta expression did not immediately induce apoptosis. Our data demonstrate in vivo differentiation from DN3 to DN4 cell in the absence of TCRbeta/gammadelta expression in the foetal thymus, and after hydrocortisone treatment of adult mice. PMID- 17273997 TI - TLR pathways and IFN-regulatory factors: to each its own. AB - TLR trigger the induction of type I IFN (IFN-alpha/beta), providing a crucial mechanism of anti-viral defense. Until recently, TLR were thought to induce type I IFN responses by activating two transcription factors which belong to the IFN regulatory factor (IRF) family, IRF-3 and IRF-7. TLR-3 and TLR-4 induce IFN-beta by activating IRF-3; TLR-9 induces IFN-alpha and IFN-beta through IRF-7, at least when engaged by type A CpG oligonucleotides (CpG-A) in plasmacytoid DC (pDC). In this issue of the European Journal of Immunology, it is demonstrated that TLR-9 induces IFN-beta when engaged by type B CpG oligonucleotides (CpG-B) in myeloid DC and macrophages. Remarkably, this response is independent of IRF-3/7 and, in fact, requires another IRF family member, IRF-1. IRF-1 is recruited by TLR-9 through the adaptor MyD88. Deficiency of the TLR-9-->IRF-1-->IFN-beta pathway results in impaired anti-viral responses not only in vitro but also in vivo. These results demonstrate that TLR induce IFN-alpha or IFN-beta responses by activating distinct IRF, depending on the TLR ligand and the cell type. These distinct TLR-IRF pathways may allow the immune system to tailor its responses to viral pathogens. PMID- 17273998 TI - Therapeutic human papillomavirus DNA vaccination strategies to control cervical cancer. AB - A persistent human papillomavirus (HPV) infection is considered causal and necessary for the continued growth of cervical cancer. Thus, vaccination against HPV represents a plausible approach to prevent and treat cervical cancer. A report in the current issue of the European Journal of Immunology describes a therapeutic HPV DNA vaccination strategy using the HPV-16 E7 antigen fused to the invariant chain to enhance the E7-specific CD8+ and CD4+ T cell immune responses, resulting in a potent anti-tumor effect against E7-expressing tumors. Continued exploration of HPV therapeutic DNA vaccines may lead to eventual clinical application. PMID- 17273999 TI - Interferon-regulatory-factor 1 controls Toll-like receptor 9-mediated IFN-beta production in myeloid dendritic cells. AB - Activation of interferon regulatory factor (IRF)-3 and/or IRF-7 drives the expression of antiviral genes and the production of alpha/beta IFN, a hallmark of antiviral responses triggered by Toll-like receptors (TLR). Here we describe a novel antiviral signaling pathway operating in myeloid (m) dendritic cells (DC) and macrophages that does not require IRF-3 and/or IRF-7 but is driven by IRF-1. IRF-1 together with myeloid differentiation factor 88 (MyD88) or IL-1 receptor associated kinase (IRAK)-1 triggered IFN-beta promoter activation. IRF-1 physically interacted with MyD88 and activation of mDC via TLR-9 induced IRF-1 dependent IFN-beta production paralleled by rapid transcriptional activation of IFN-stimulated genes. The NF-kappaB-dependent production of pro-inflammatory cytokines, however, was not influenced by IRF-1. TLR-9 signaling through this pathway conferred cellular antiviral resistance while IRF-1-deficient mice displayed enhanced susceptibility to viral infection. These results demonstrate that TLR-9 activation of mDC and macrophages contributes to antiviral immunity via IRF-1. PMID- 17274000 TI - IL-18 enhances IFN-gamma-induced production of CXCL9, CXCL10, and CXCL11 in human keratinocytes. AB - IL-18 is involved in the pathogenesis of atopic dermatitis, psoriasis, and allergic contact dermatitis. CXCL9, CXCL10, and CXCL11 recruit type 1 T cells, and the production of these chemokines by keratinocytes is enhanced in these dermatoses. We examined the in vitro effects of IL-18 on IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production in human keratinocytes. IL-18 enhanced the IFN gamma-induced secretion and mRNA expression of CXCL9, CXCL10, and CXCL11 in parallel to the activation of NF-kappaB, STAT1, and IFN-regulatory factor (IRF) 1. Antisense oligonucleotides against NF-kappaB p50, p65, or STAT1 suppressed CXCL9, CXCL10, and CXCL11 production, and antisense IRF-1 suppressed CXCL11 production. Inhibitors of PI3 K, p38 MAPK, and MEK suppressed IL-18 plus IFN gamma-induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF 1 activities. IL-18 induced phosphorylation of ERK and Akt, while IFN-gamma induced phosphorylation of p38 MAPK. These results suggest that IL-18 may potentiate IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production in keratinocytes by activating NF-kappaB, STAT1, or IRF-1 through PI3 K/Akt and MEK/ERK pathways. These effects of IL-18 may promote the infiltration of type 1 T cells into lesions with inflammatory dermatoses and amplify the skin inflammation. IL-18 may act as a pro-inflammatory cytokine in these dermatoses and thus is a candidate therapeutic target. PMID- 17274001 TI - CD38 cross-linking enhances TLR-induced B cell proliferation but decreases IgM plasma cell differentiation. AB - It is becoming increasingly clear that the regulation of proliferation and differentiation of B cells to plasma cells involves the integration of a variety of intracellular signals provided by receptors of both the adaptive and innate immune system. The cross-linking of the surface molecule CD38 induces calcium mobilization, protein phosphorylation and NF-kappaB translocation into the nucleus, ultimately leading to proliferation and isotype switching toward IgG1. Here we describe (a) the effect on B cell activation of stimulating through both CD38 and Toll-like receptors 4, 7 and 9; and (b) that CD38 cross-linking increases the number of proliferating cells and the rate of proliferation in LPS stimulated B cells by a Bruton's tyrosine kinase- and protein kinase C-dependent mechanism. In contrast, CD38 cross-linking reduces the number of cells committed to IgM plasma cell differentiation as measured by the number of CD138+ cells, antibody secretion, and the expression of PAX5, Bcl6 and Blimp-1. Since a putative ligand for CD38 is expressed by germinal center follicular dendritic cells, and CD38 expression is down-regulated in germinal center B cells, we speculate that CD38 might participate in the outcome of post-germinal center antibody responses. PMID- 17274002 TI - DNA vaccine encoding endosome-targeted human papillomavirus type 16 E7 protein generates CD4+ T cell-dependent protection. AB - Human papillomavirus type 16 is commonly implicated in cervical cancers. The viral genome encodes potential targets like the oncoprotein E7, expressed in transformed cells but thought to represent a poorly immunogenic antigen. We describe in this work a DNA-based vaccination protocol aimed at inducing an efficient anti-E7 immune response in vivo. Plasmids allowing the expression of the E7 protein in distinct cellular compartments were generated and assayed in an in vivo model of tumor growth. Our data demonstrate that mice vaccinated with a plasmid encoding for an E7 protein fused to a domain of the MHC class II associated invariant chain (IiE7) were protected against tumor challenge. Mice immunized against an ubiquitinated form of E7 (Ub(Ala)E7) failed to control tumor growth. Protection induced by IiE7 was correlated with the development of CD8+ CTL and required the presence of CD4+ cells. In vitro studies confirmed that the IiE7 fusion protein was expressed at high levels in the endosomal compartment of transfected cells, while the natural and the ubiquitin-modified form of E7 were mainly nuclear. The present study suggests that an efficient anti-tumor response can be induced in vivo by DNA constructs encoding for E7 protein forms localizing at the endosomal compartment. PMID- 17274003 TI - Secondary immunisation with high-dose heterologous peptide leads to CD8 T cell populations with reduced functional avidity. AB - Expansion of high- or low-avidity CD8 T cells in vitro inversely correlates with the concentration of peptide ligand present during culture. In contrast, the selective enrichment of high- or low-avidity T cell populations in vivo using peptide immunisation is not well documented. In our study, a single immunisation with different doses of wild-type peptide or a variant peptide able to stimulate CTL responses cross-reactive with wild-type peptide failed to shift the average avidity of the responding CD8 T cell population specific to either peptide. However, in contrast to homologous prime-boost immunisation, heterologous prime boost immunisation incorporating high doses of the second immunogen resulted in peptide-specific CD8 T cell populations polarized toward a low average functional avidity. These data suggest that sequential exposure to structurally related viral peptides could impair rather than promote anti-viral immunity by lowering the avidity of the responding CD8 T cell population. This study has implications for improving vaccine strategies against viruses and tumours and enhances our understanding of heterologous immunity during sequential viral infection. PMID- 17274004 TI - The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. AB - 1Alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) has important effects on the growth and function of multiple cell types. These pleiotropic effects of 1,25(OH)2D3 are mediated through binding to the vitamin D receptor (VDR). Several polymorphisms of the human VDR gene have been identified, with the FokI polymorphism resulting in VDR proteins with different structures, a long f-VDR or a shorter F-VDR. The aim of this study was to investigate the functional consequences of the FokI polymorphism in immune cells. In transfection experiments, the presence of the shorter F-VDR resulted in higher NF-kappaB- and NFAT-driven transcription as well as higher IL-12p40 promoter-driven transcription. Marginal differences were observed for AP-1-driven transcription, and no differential effects were observed for transactivation of a classical vitamin D-responsive element. Concordantly, in human monocytes and dendritic cells with a homozygous short FF VDR genotype, expression of IL-12 (mRNA and protein) was higher than in cells with a long ff VDR genotype. Additionally, lymphocytes with a short FF VDR genotype proliferated more strongly in response to phytohemagglutinin. Together, these data provide the first evidence that the VDR FokI polymorphism affects immune cell behavior, with a more active immune system for the short F-VDR, thus possibly playing a role in immune-mediated diseases. PMID- 17274007 TI - Hypocalcemia as a presentation for multifocal osteosarcoma. AB - We report the case of a 16-year-old male with multifocal osteosarcoma presented with symptomatic hypocalcemia. The patient presented signs of hypocalcemia accompanied by generalized bone pain and a femoral mass. Further evaluation revealed secondary hyperparathyroidism, highly elevated alkaline phosphatase levels, and generalized sclerotic and lytic lesions. Biopsy confirmed osteosarcomatosis. Despite aggressive chemotherapy, he died from progressive disease 2 months after diagnosis. The course of disease in this patient suggests that hypocalcemia reflects a poor prognosis. PMID- 17274005 TI - Patterns of variation in DNA segments upstream of transcription start sites. AB - It is likely that evolutionary differences among species are driven by sequence changes in regulatory regions. Likewise, polymorphisms in the promoter regions may be responsible for interindividual differences at the level of populations. We present an unbiased survey of genetic variation in 2-kb segments upstream of the transcription start sites of 28 protein-coding genes, characterized in five population groups of different geographic origin. On average, we found 9.1 polymorphisms and 8.8 haplotypes per segment with corresponding nucleotide and haplotype diversities of 0.082% and 58%, respectively. We characterized these segments through different summary statistics, Hardy-Weinberg equilibria fixation index (Fst) estimates, and neutrality tests, as well as by analyzing the distributions of haplotype allelic classes, introduced here to assess the departure from neutrality and examined by coalescent simulations under a simple population model, assuming recombinations or different demography. Our results suggest that genetic diversity in some of these regions could have been shaped by purifying selection and driven by adaptive changes in the other, thus explaining the relatively large variance in the corresponding genetic diversity indices loci. However, some of these effects could be also due to linkage with surrounding sequences, and the neutralists' explanations cannot be ruled out given uncertainty in the underlying demographic histories and the possibility of random effects due to the small size of the studied segments. PMID- 17274008 TI - Small pituitary size in children with Fanconi anemia. AB - BACKGROUND: Fanconi anemia (FA) is a genetic disorder associated with multiple congenital anomalies, bone marrow failure, and pituitary hypofunction including hypogonadism, thyroid dysfunction, and growth hormone (GH) deficiency. PROCEDURE: Among 44 patients with FA referred to Cincinnati Children's Hospital Medical Center (CCHMC) between 1975 and 2005, 33 had neuroimaging studies, including 11 cranial magnetic resonance imaging (MRIs). Two separate measurements per patient from these MRIs were used to evaluate pituitary height compared to on-site control data of similar measurements of cranial MRIs on 22 age and gender-matched children without any pathology involving the hypothalamic-pituitary system. Growth pattern and endocrine studies were reviewed to assess potential correlation with pituitary size. RESULTS: When compared to the age-gender matched on-site control sample, the mean pituitary height of FA patients was significantly smaller (P < 0.0001; mean +/- SE from mixed effects model with age and gender as covariates: 3.96 +/- 0.32 vs. 5.76 +/- 0.24). Upon further adjusting for the effect of the small head size by including bi-parietal diameter (BPD) as a covariate, the difference remained statistically significant (P = 0.0013). Findings on the growth pattern and endocrinological measurements are as follows: 50% of patients with small pituitary gland were short. GH and adrenal function tests were normal in all tested patients. Thyroid, pubertal status, and glucose regulation were abnormal in 30, 50, and 75% of patients tested. CONCLUSIONS: Children with FA tend to have unsuspected small pituitary glands beyond what is expected from the effects of their stunted growth. Further studies are required to reveal the clinical implications of this finding. PMID- 17274010 TI - Human manipulative behavior in the Central European Late Eneolithic and Early Bronze Age: humeral bilateral asymmetry. AB - It is assumed that the transition from the Late Eneolithic to the Early Bronze Age in Central Europe was associated with substantial changes in subsistence and the perception of gender differences. However, the archeological record itself does not entirely support this model. Alternatively, this transition may be interpreted as a continuous process. We used asymmetry in external dimensions, and asymmetry in size and distribution of cortical tissue of humeri to elucidate the nature of this transition with respect to differences in manipulative behavior. The total sample of 67 individuals representing five archaeological cultures was used. The results indicate that the pattern of asymmetry of the humeral external measurements and the cross-sectional parameters taken at 35% of humeral biomechanical length remain stable during the Late Eneolithic and Early Bronze Age. However, females of both periods show fluctuating asymmetry for all of the cross-sectional parameters, but directional asymmetry for biomechanical length. Males are nonsignificantly shifted from the line of equivalence for biomechanical length, but exhibit directional asymmetry for the cortical area and polar moment of area. Only distal articular breadth yields fluctuating asymmetry for both females and males in both periods. Thus, the transition from the Late Eneolithic to the Early Bronze Age can be seen as a continuous process that probably affected only a limited part of human activities. We interpret the differences between females and males of both periods as evidence of gender specific activities; males might have been associated with extra-domestic agricultural labor that resulted in asymmetrical manipulative loading and females with domestic labor with symmetrical manipulative loading in both periods. PMID- 17274009 TI - Signal peptide variants that impair secretion of pancreatic secretory trypsin inhibitor (SPINK1) cause autosomal dominant hereditary pancreatitis. AB - Variants of the SPINK1 gene encoding pancreatic secretory trypsin inhibitor have been described in association with chronic pancreatitis (CP). These alterations are believed to cause a loss of function by either impairing the trypsin inhibitory activity or reducing expression. Here we report two novel SPINK1 variants in exon 1 that affect the secretory signal peptide. The disease associated c.41T>G (p.L14R) alteration was found in two European families with autosomal dominant hereditary pancreatitis, whereas the c.36G>C (p.L12F) variant was identified as a frequent alteration in subjects of African descent. The functional effects of both alterations and the previously reported c.41T>C (p.L14P) variant were characterized by activity assays and Western blots of wild type and mutant SPINK1 expressed in human embryonic kidney 293T and Chinese hamster ovary cells. Alterations p.L14R and p.L14P destined the inhibitor for rapid intracellular degradation and thereby abolished SPINK1 secretion, whereas the p.L12F variant showed no detrimental effect. The results provide the first clear experimental demonstration that alterations that markedly reduce SPINK1 expression are associated with classic hereditary pancreatitis. Therefore, these variants should be classified as severe and regarded as disease-causing rather than disease-modifiers. PMID- 17274011 TI - The impact of reproduction on gambian women: does controlling for phenotypic quality reveal costs of reproduction? AB - Life history theory predicts that where resources are limited, investment in reproduction will cause a decline in body condition and ultimately may lower survival rates. We investigate the relationship between reproduction and mortality in women in rural Gambia. We use a number of different measures of reproductive investment: the timing of reproduction, intensity of reproduction, and cumulative reproductive investment (parity). Though giving birth is clearly a risk factor for increased mortality, we find limited evidence that the timing, intensity, or cumulative effects of reproduction have a survival cost. Instead, there is some evidence that women who have invested heavily in reproduction have higher survival than women with lower reproductive investment: both high parity and late age at last reproduction are associated with high survival. The only evidence for any cost of reproduction is that women who have given birth to twins (considered a marker of heavy investment in reproduction) have higher mortality rates than other women, after the age of 50 years. A potential confounding factor may be differences in health between women: particularly healthy women may be able to invest substantially in both reproduction and their own survival, leading to the positive correlations between survival and both parity and age at last birth we observe. To control for differences in health between women, we reanalyze the relationship between reproduction and mortality but include variables correlating with health in our models (height, BMI, and hemoglobin). Even when controlling for health, the positive correlation between investment in reproduction and survival remains unchanged. PMID- 17274012 TI - Spatio-genetic population structure in mustached tamarins, Saguinus mystax. AB - Dispersal and philopatry influence gene flow and thus the spatio-genetic structure within and between populations. In callitrichids the flexible social and mating system corresponds with a variable migration pattern where both sexes might be philopatric or might disperse. We investigated the relationship between the spatio-genetic structure and migration patterns in a population of mustached tamarins, Saguinus mystax. Using the rapidly evolving hypervariable region I (HVI) of the mitochondrial control region and 11 microsatellite markers we detected a high variation (HVI: 16 haplotypes in 69 individuals; microsatellites: H(O) = 0.75, average: 7.45 alleles/locus), with mating partners usually not sharing the same haplotype, indicating that matings are generally between partners that are not closely related. Similar high variance of haplotype differences for male-male and female-female pairs, along with a slightly higher number of haplotype differences in males show that both sexes habitually migrate. Spatial analyses suggest that females usually migrate longer distances, corresponding to very limited breeding positions for females in a polyandrous social mating system. PMID- 17274013 TI - Thomas Jefferson's Y chromosome belongs to a rare European lineage. AB - We have characterized the Y chromosome carried by President Thomas Jefferson, the general rarity of which supported the idea that he, or a patrilineal relative, fathered the last son of his slave Sally Hemings. It belongs to haplogroup K2, a lineage representing only approximately 1% of chromosomes worldwide, and most common in East Africa and the Middle East. Phylogenetic network analysis of its Y STR (short tandem repeat) haplotype shows that it is most closely related to an Egyptian K2 haplotype, but the presence of scattered and diverse European haplotypes within the network is nonetheless consistent with Jefferson's patrilineage belonging to an ancient and rare indigenous European type. This is supported by the observation that two of 85 unrelated British men sharing the surname Jefferson also share the President's Y-STR haplotype within haplogroup K2. Our findings represent a cautionary tale in showing the difficulty of assigning individual ancestry based on a Y-chromosome haplotype, particularly for rare lineages where population data are scarce. PMID- 17274014 TI - Yaws disease in a wild gorilla population and its impact on the reproductive status of males. AB - We evaluated the prevalence of skin lesions in a gorilla population in the Republic of Congo. The observed lesions were typical of yaws, a treponematosis described in gorillas and humans living in tropical regions. Among the 377 gorillas identified, 17% presented skin lesions, mainly on their faces. The worst cases presented physical handicaps because of the deep lesions. As in humans, lesions break out when individuals are young. Lesions were more prevalent among males than females above 8 years old. This sex-bias prevalence could result from the behavioral characteristics of males through a greater exposure to wounds. Lesions were also more prevalent in unmated adult males (either solitaries or those living in nonbreeding groups) than in males leading breeding groups. In the case of the latter, nonaffected and affected leading males had a similar number of infants and juveniles. Still, none of the leading males ever presented serious handicaps because of the skin lesions. This suggests that adult females could favor males without lesions. Finally, lesions were more prevalent among immature animals in nonbreeding groups than in breeding groups, suggesting that either young animals with lesions disperse earlier from their natal groups, or that the disease spreads faster in nonbreeding groups. Our results provide some insights into the spread of a disease in a wild population. Further studies are required to determine if the vigor of males affects the development of the disease and if affected individuals experience social discrimination inducing a negative impact on population dynamics. PMID- 17274015 TI - A PM3/d specific reaction parameterization for iron atom in the hydrogen abstraction catalyzed by soybean lipoxygenase-1. AB - This paper reports a specific reaction parameter (SRP) PM3/d model for iron that can reproduce the DFT/MM results of the hydrogen abstraction reaction from the C11 position of linoleic acid by the Soybean lipoxygenase-1 enzyme. A suite of nonlinear optimization methods is outlined for semiempirical parameter development based on integrated evolutionary (genetic) and direction set minimization algorithms. The PM3/d-SRP Fe parameters are derived along three consecutive steps. The final parameterization step includes the effect of the whole enzyme in order to get a better quantum mechanical/molecular mechanical description. PMID- 17274016 TI - A semiempirical free energy force field with charge-based desolvation. AB - The authors describe the development and testing of a semiempirical free energy force field for use in AutoDock4 and similar grid-based docking methods. The force field is based on a comprehensive thermodynamic model that allows incorporation of intramolecular energies into the predicted free energy of binding. It also incorporates a charge-based method for evaluation of desolvation designed to use a typical set of atom types. The method has been calibrated on a set of 188 diverse protein-ligand complexes of known structure and binding energy, and tested on a set of 100 complexes of ligands with retroviral proteases. The force field shows improvement in redocking simulations over the previous AutoDock3 force field. PMID- 17274017 TI - Neural mechanisms of evoked oscillations: stability and interaction with transient events. AB - There is increasing evidence that early event-related potentials are a result of phase alignment of ongoing background oscillations of the electroencephalogram rather than additive amplitude modulation. Steady state visual-evoked potentials (ssVEPs) can be recorded using an intensity modulated stimulus, resulting in an evoked brain response at a known frequency, i.e. the stimulation frequency. Given this property, the ssVEP is ideally suited for examining the relationship between single-trial fluctuations in phase/amplitude and the evoked brain potential resulting from averaging across trials. To address this issue, the current study investigated the contribution of single trial power and intertrial phase locking to ssVEP generation by presenting a peripheral flicker. Further, transient stimuli were presented during flicker and at three increasing latency lags following flicker offset to examine (1) to what extent a stimulus can disturb the ssVEP oscillation and (2) how phase alignment during P1-N1-P2 time windows is affected during presence of evoked oscillations. The former assessment evaluates the stability of ssVEPs and the latter the phase alignment processes to transient stimuli under experimentally induced background oscillations. We observed that ssVEPs are a result of phase alignment rather than single trial amplitude modulation. In addition, ssVEP oscillations were not disturbed by transient stimuli. Finally, phase alignment in P1-N1-P2 time windows was distorted during and shortly after steady state stimulation. We conclude that ssVEPs represent strongly phase locked oscillations sharing the same generation mechanisms as early evoked potentials. PMID- 17274018 TI - An fMRI study of canonical and noncanonical word order in German. AB - Understanding a complex sentence requires the processing of information at different (e.g., phonological, semantic, and syntactic) levels, the intermediate storage of this information and the unification of this information to compute the meaning of the sentence information. The present investigation homed in on two aspects of sentence processing: working memory and reanalysis. Event-related functional MRI was used in 12 healthy native speakers of German, while they read sentences. Half of the sentences had unambiguous initial noun-phrases (masculine nominative, masculine accusative) and thus signaled subject-first (canonical) or object-first (noncanonical) sentences. Noncanonical unambiguous sentences were supposed to entail greater demand on working memory, because of their more complex syntactic structure. The other half of the sentences had case-ambiguous initial noun-phrases (feminine gender). Only the second unambiguous noun-phrase (eighth position in the sentences) revealed, whether a canonical or noncanonical word order was present. Based on previous data it was hypothesized that ambiguous noncanonical sentences required a recomputation of the sentence, as subjects would initially commit to a subject first reading. In the respective contrasts two main areas of brain activation were observed. Unambiguous noncanonical sentences elicited more activation in left inferior frontal cortex relative unambiguous canonical sentences. This was interpreted in conjunction with the greater demands on working memory in the former condition. For noncanonical ambiguous relative to canonical ambiguous sentences, an activation of the left supramarginal gyrus was revealed, which was interpreted as a reflection of the reanalysis-requirements induced by this condition. PMID- 17274019 TI - fMRI analysis for motor paradigms using EMG-based designs: a validation study. AB - The goal of the present validation study is to show that continuous surface EMG recorded simultaneously with 3T fMRI can be used to identify local brain activity related to (1) motor tasks, and to (2) muscle activity independently of a specific motor task, i.e. spontaneous (abnormal) movements. Five healthy participants performed a motor task, consisting of posture (low EMG power), and slow (medium EMG power) and fast (high EMG power) wrist flexion-extension movements. Brain activation maps derived from a conventional block design analysis (block-only design) were compared with brain activation maps derived using EMG-based regressors: (1) using the continuous EMG power as a single regressor of interest (EMG-only design) to relate motor performance and brain activity, and (2) using EMG power variability as an additional regressor in the fMRI block design analysis to relate movement variability and brain activity (mathematically) independent of the motor task. The agreement between the identified brain areas for the block-only design and the EMG-only design was excellent for all participants. Additionally, we showed that EMG power variability correlated well with activity in brain areas known to be involved in movement modulation. These innovative EMG-fMRI analysis techniques will allow the application of novel motor paradigms. This is an important step forward in the study of both the normally functioning motor system and the pathophysiological mechanisms in movement disorders. PMID- 17274020 TI - Prefrontal cortex activity is reduced in gambling and nongambling substance users during decision-making. AB - OBJECTIVE: Poor decision-making is a hallmark of addiction, whether to substances or activities. Performance on a widely used test of decision-making, the Iowa Gambling Task (IGT), can discriminate controls from persons with ventral medial frontal lesions, substance-dependence, and pathological gambling. Positron emission tomography (PET) studies indicate that substance-dependent individuals show altered prefrontal activity on the task. Here we adapted the IGT to an fMRI setting to test the hypothesis that defects in ventral medial and prefrontal processing are associated with impaired decisions that involve risk but may differ depending on whether substance dependence is comorbid with gambling problems. METHOD: 18 controls, 14 substance-dependent individuals (SD), and 16 SD with gambling problems (SDPG) underwent fMRI while performing a modified version of the IGT. RESULT: Group differences were observed in ventral medial frontal, right frontopolar, and superior frontal cortex during decision-making. Controls showed the greatest activity, followed by SDPG, followed by SD. CONCLUSION: Our results support a hypothesis that defects in ventral medial frontal processing lead to impaired decisions that involve risk. Reductions in right prefrontal activity during decision-making appear to be modulated by the presence of gambling problems and may reflect impaired working memory, stimulus reward valuation, or cue reactivity in substance-dependent individuals. PMID- 17274021 TI - Relationship between task-related gamma oscillations and BOLD signal: new insights from combined fMRI and intracranial EEG. AB - Cognitive neuroscience relies on two sets of techniques to map the neural networks underlying cognition in humans: recordings of either regional metabolic changes (fMRI or PET) or fluctuations in the neural electromagnetic fields (EEG and MEG). Despite major advances in the last few years, an explicit linkage between the two is still missing and the neuroimaging community faces two complementary but unrelated sets of functional descriptions of the human brain. Such an explicit framework, linking the two approaches in potentially complex cognitive tasks and in a variety of brain regions would permit to combine them into fine spatio-temporally-grained human brain mapping procedures. We combined fMRI and intra-cranial EEG recordings of the same epileptic patients during a semantic decision task and found a close spatial correspondence between regions of fMRI activations and recording sites showing EEG energy modulations in the gamma range (>40 Hz). Our findings further support previous findings that gamma band modulations co-localize with BOLD variations and also indicate that fMRI may be used as a constraint to improve source reconstruction of gamma band EEG responses. PMID- 17274022 TI - Dissociation of response inhibition and performance monitoring in the stop signal task using event-related fMRI. AB - We examined the neural substrate of motor response inhibition and performance monitoring in the stop signal task (SST) using event-related functional magnetic resonance imaging (fMRI). The SST involves a go task and the occasional requirement to stop the go response. We posit that both the go and the stop phases of the SST involve components of inhibition and performance monitoring. The goal of this study was to determine whether inhibition and performance monitoring during go and stop phases of the task activated different networks. We isolated go-phase activities underlying response withholding, monitoring, and sensorimotor processing and contrasted these with successful inhibition to identify the substrate of response inhibition. Error detection activity was isolated using trials in which a stop signal appeared but the response was executed. These trials were modeled as a hand-specific go trial followed by error processing. Cognitive go-phase processes included response withholding and monitoring and activated right prefrontal and midline networks. Response withdrawal additionally activated right inferior frontal gyrus and basal ganglia (caudate). Error detection invoked by failed inhibition activated dorsal anterior cingulate cortex (dACC) and right middle frontal Brodmann's area 9. Our results confirm that there are distinct aspects of inhibition and performance monitoring functions which come into play at various phases within a given trial of the SST, and that these are separable using fMRI. PMID- 17274023 TI - Estimating the number of independent components for functional magnetic resonance imaging data. AB - Multivariate analysis methods such as independent component analysis (ICA) have been applied to the analysis of functional magnetic resonance imaging (fMRI) data to study brain function. Because of the high dimensionality and high noise level of the fMRI data, order selection, i.e., estimation of the number of informative components, is critical to reduce over/underfitting in such methods. Dependence among fMRI data samples in the spatial and temporal domain limits the usefulness of the practical formulations of information-theoretic criteria (ITC) for order selection, since they are based on likelihood of independent and identically distributed (i.i.d.) data samples. To address this issue, we propose a subsampling scheme to obtain a set of effectively i.i.d. samples from the dependent data samples and apply the ITC formulas to the effectively i.i.d. sample set for order selection. We apply the proposed method on the simulated data and show that it significantly improves the accuracy of order selection from dependent data. We also perform order selection on fMRI data from a visuomotor task and show that the proposed method alleviates the over-estimation on the number of brain sources due to the intrinsic smoothness and the smooth preprocessing of fMRI data. We use the software package ICASSO (Himberg et al. [ 2004]: Neuroimage 22:1214-1222) to analyze the independent component (IC) estimates at different orders and show that, when ICA is performed at overestimated orders, the stability of the IC estimates decreases and the estimation of task related brain activations show degradation. PMID- 17274024 TI - Evidence for neural accommodation to a writing system following learning. AB - Native English speakers with no knowledge of Chinese were trained on 60 Chinese characters according to one of three mapping conditions: orthography to pronunciation and meaning (P + M), orthography to pronunciation (P), and orthography to meaning (M). Following the training, fMRI scans taken during passive viewing of Chinese characters showed activation in brain regions that partially overlap the regions found in studies of skilled Chinese readers, but typically not found in alphabetic readers. Areas include bilateral middle frontal (BA 9), right occipital (BA 18/19), and fusiform (BA 37) regions. The activation pattern of Chinese characters was similar across the three groups. However, peak location was different in the left middle frontal region between groups. Direct contrasts between the groups also revealed stronger activation of left middle frontal in the P + M group. The results suggest that learners acquired skill in reading Chinese characters using a brain network similar to that used by Chinese native speakers. The results are consistent with the system accommodation hypothesis: The brain's reading network accommodates to features of an acquired writing system. PMID- 17274025 TI - Peptide insertion, positioning, and stabilization in a membrane: insight from an all-atom molecular dynamics simulation. AB - Peptide insertion, positioning, and stabilization in a model membrane are probed via an all-atom molecular dynamics (MD) simulation. One peptide (WL5) is simulated in each leaflet of a solvated dimyristoylglycero-3-phosphate (DMPC) membrane. Within the first 5 ns, the peptides spontaneously insert into the membrane and then stabilize during the remaining 70 ns of simulation time. In both leaflets, the peptides localize to the membrane interface, and this localization is attributed to the formation of peptide-lipid hydrogen bonds. We show that the single tryptophan residue in each peptide contributes significantly to these hydrogen bonds; specifically, the nitrogen heteroatom of the indole ring plays a critical role. The tilt angles of the indole rings relative to the membrane normal in the upper and lower leaflets are approximately 26 degrees and 54 degrees , respectively. The tilt angles of the entire peptide chain are 62 degrees and 74 degrees . The membrane induces conformations of the peptide that are characteristic of beta-sheets, and the peptide enhances the lipid ordering in the membrane. Finally, the diffusion rate of the peptides in the membrane plane is calculated (based on experimental peptide concentrations) to be approximately 6 A(2)/ns, thus suggesting a 500 ns time scale for intermolecular interactions. PMID- 17274026 TI - The influence of intrinsic coagulation pathway on blood platelets activation by oxidized cellulose. AB - Oxidized cellulose is an effective hemostat that works naturally to aid in blood coagulation. The mechanism of its action is not very well understood. Little effect on blood coagulation, but a pronounce decrease in platelet count has been reported upon the addition of the oxidized cellulose to the whole blood. As a marker of platelet activation and aggregation we used serotonin release reaction and turbidity changes in time. We found that oxidized cellulose did not activate washed platelets reconstituted in plasma-free medium or plasma-free medium with fibrinogen; no reduction of platelet count was observed. Serotonin release in platelet-rich plasma incubated with oxidized cellulose started in the range from 5 to 10 min. Serotonin release from platelets reconstituted in plasma deficient in either coagulation factor V, VIII, IX, or XII was delayed. Blood platelets activation by oxidized cellulose requires calcium ions present in dispersion of oxidized cellulose. Factor XIII deficiency had no influence on blood platelets activation by oxidized cellulose. Our results clearly indicate the significance of intrinsic coagulation pathway activation on blood platelets activation by oxidized cellulose and so indirectly on the hemostyptic effect of oxidized cellulose. PMID- 17274027 TI - Effects on gingival cells of hydroxyapatite immobilized on poly(ethylene-co-vinyl alcohol). AB - Hydroxyapatite was immobilized on poly(ethylene-co-vinyl alcohol) (EVA) by alternate soaking in aqueous CaCl(2) and Na(2)HPO(4) solutions, followed by carboxyl groups introduction through ozone exposure in order to investigate the nature of the gingival cells, to control their proliferation and properties and to develop a highly organized hybrid implant possessing periodontium. Human gingival cells were cultured on the ozone-exposed EVA, collagen-immobilized EVA, hydroxyapatite-immobilized EVA, and a conventional tissue culture dish. Cell proliferation was highest on the tissue culture dish and lowest on the hydroxyapatite-immobilized EVA. The results of RT-PCR of gingival cells on hydroxyapatite-immobilized EVA shows that mRNAs expressed in bone and periodontal ligament were determined. Furthermore, alkaline phosphatase activity and ELISA assay revealed that gingival cells acquired the osteoblastic properties when cultured on hydroxyapatite-immobilized EVA, suggesting that the periodontium might be regenerated around implants using gingival cells. PMID- 17274028 TI - Effects of mannosylated glycopolymers on specific interaction to bone marrow hematopoietic and progenitor cells derived from murine species. AB - Poly[N-pvinylbenzyl-O-D-galactopyranosyl-(1-4)-D-glucoamide], poly[N-pvinylbenzyl O-D-glucopyranosyl-(1-4)-D-glucoamide], and poly[N-p-vinylbenzyl-O-mannopyranosyl (1-4)-D-gluconamide] (referred to as PVLA, PVMA, and PV-Man) are polystyrene derivatives that contain galactose, glucose, and mannose moieties, which interact with hematopoietic cells (HCs). To clarify the specific interaction between the glucopolymers and hematopoietic cells, glycopolymers labeled with fluorescent isothiocyanate (FITC) were used to follow the specific interaction, which was visualized by confocal laser microscopy. We found that PV-Man binds strongly to HCs, probably because of a specific interaction mediated by specific receptors present on the cell membrane, while some cytotoxicity when was observed when PV Man interacted with the cell membrane. The fluorescence intensity between PV-Man and HCs was up to four-fold (0.14 +/- 0.04) that of PVMA and PVLA with hematopoietic HCs (0.033 +/- 0.01). Moreover, cellular fluorescence increased significantly with increasing incubation time and increasing polymer concentration. Using hematopoietic lineage-specific antibodies, cells were stained and analyzed by flow cytometry to confirm which HCs showed specific binding with glycopolymers, especially hematopoietic stem cells and progenitor cells (c-kit+), B-lymphocyte progenitor cells (B220+), monocyte cells (CD11b+), and erythrocytes (Ter119+). PMID- 17274029 TI - Nanostructural characteristics, mechanical properties, and osteoblast response of spark plasma sintered hydroxyapatite. AB - This study aimed to fabricate bulk nanostructured hydroxyapatite (HA) pellets with improved properties using spark plasma sintering (SPS) for orthopedic applications. Spray-dried nanostructured HA (nSD-HA) powders were consolidated using the rapid SPS processing. The SPS processed nSD-HA was characterized using Raman spectroscopy and field emission scanning electron microscopy (FESEM). Mechanical properties of the consolidates were also evaluated through indentation approach. The nanostructures ( approximately 80 nm in grain size) of the starting powders were successfully retained after the SPS processing operated at 950 degrees C with <15 min holding time. The SPS consolidated nSD-HA showed promising mechanical properties, approximately 118 GPa for Young's modulus, and up to 2.22 MPa m(0.5) for fracture toughness. SPS holding time showed minor influence on the phases of the pellets. Furthermore, the spheroidized nanostructured HA retained the HA structure after the SPS consolidation. Preliminary cytotoxicity and cell attachment studies were also carried out using a human osteoblast cell line hFOB 1.19. Enhanced cell attachment and proliferation on the nanostructured pellets were revealed. The presence of the nanostructures accounts mainly for the enhanced mechanical properties and promoted proliferation of the osteoblast cells. This study suggests that the SPS technique is an appropriate process for fabrication of bulk nSD-HA from nanostructured powder. PMID- 17274030 TI - Post-augmentation bladder perforation during urodynamic investigation. AB - AIMS: To report for the first time bladder rupture during filling cystometry many years after bladder augmentation. METHODS: A 17-year-old girl with T10 meningomyelocele had received an ileocystoplasty, continent catheterizable stoma, and bladder neck sling for neurogenic bladder dysfunction and intractable incontinence 8 years previously. She was continent with clean intermittent self catheterization four times per day. Yearly urodynamics showed a bladder capacity of up to 700 ml with good compliance and low bladder pressures. In March 2006, filling cystometry was performed. RESULTS: Bladder pressure was normal until 400 ml, after which it increased due to lower compliance. At 620 ml filling, the detrusor pressure was 52 cm H2O, and the patient complained suddenly of abdominal discomfort and bilateral shoulder pain, and the infusion was stopped. A catheter was placed and cystography showed intraperitoneal leakage along the left lateral bladder aspect and at the Mitrofanoff insertion site on the bladder dome. The perforations were closed via a midline incision and a ventriculoperitoneal shunt had to be exteriorized. There were no post-operative complications and a control cystogram revealed no leakage. CONCLUSIONS: Augmentation ileocystoplasty has been used extensively in order to increase bladder capacity and decrease intravesical pressure. Although spontaneous or traumatic perforation of the augmented bladder has been described previously, it was never reported in correlation with urodynamic investigation. Extreme caution is warranted in the face of decreased compliance during filling cystometry in these patients, even though urodynamics showed good bladder compliance and low bladder pressures many years after ileocystoplasty. PMID- 17274031 TI - Interaction of filling related sensation between anorectum and lower urinary tract and its impact on the sequence of their evacuation. A study in healthy volunteers. AB - AIMS: The anorectum and lower urinary tract (LUT) are closely related organs: anorectal and LUT dysfunction often occur concomitant, and therapeutic actions in one organ may influence function of the other. The aim of this study was to explore the physiologic relationship between anorectal and LUT function in healthy volunteers. METHODS: Two groups of healthy volunteers were studied. Anorectal and LUT sensory function was evaluated in ten volunteers during rectal balloon and bladder filling. The second group of 100 volunteers reported on defecation and micturition during five toilet visits. They graded perception on rectal and bladder fullness on a visual analogue scale and marked which organ evacuation started first. RESULTS: The volumes at which the different sensations of rectal filling during balloon distension were perceived was significantly higher with full bladder than with empty bladder (P<0.04). Five hundred toilet visits were described. Although mean perception grade of rectal fullness was significantly higher than for bladder fullness (P<0.0001), defecation started only in 36% of the reported visits before micturition. Only when the rectum was considered completely full, or the bladder completely empty, defecation occurred more frequently before micturition. In all other cases, micturition more frequently occurred before defecation. CONCLUSIONS: When the bladder is full, sensation of rectal filling is decreased. When healthy people visit the toilet to defecate, the initiation of micturition often precedes that of defecation, even if both organs are considered equally full. PMID- 17274032 TI - Refinement of the DYT15 locus in myoclonus dystonia. AB - Inherited myoclonus dystonia (MD) is an autosomal dominant disorder in which we previously mapped a novel locus to chromosome18p11 (OMIM number: 607488). Since no further informative STS markers were found within the flanking shared regions, we utilized single nucleotide polymorphisms (SNP) for fine-mapping. All known or predicted genes within this region were directly sequenced. We identified three recombinant SNPs in the distal region but none from the proximal region. Our previous linked region has now been reduced to 3.18 Mb but direct sequencing of all seven known and four predicted genes with EST support did not identify any mutations.. PMID- 17274033 TI - Genetic variation at the tau locus and clinical syndromes associated with progressive supranuclear palsy. AB - A number of different clinical syndromes have been associated with progressive supranuclear (PSP) tau pathology. Previous reports have suggested that atypical clinical phenotypes of PSP occur in familial disease, and might be associated with mutations of MAPT. We examined the association of PSP-susceptibility tau haplotypes in pathologically diagnosed PSP, separated according to initial clinical features into classic PSP and atypical PSP groups (PSP-Parkinsonism, PSP P). These patients were screened for mutations in exons 1 and 10 of MAPT. No mutations were found in 75 patients (21 PSP-P), and H1c was associated with both Richardson's syndrome and PSP-P compared with controls. Routine screening for MAPT mutations in atypical PSP is not recommended. PMID- 17274034 TI - Reliability of the Burke-Fahn-Marsden scale in a multicenter trial for dystonia. AB - BACKGROUND: The multicenter SPIDY trial (pallidal stimulation for generalized, idiopathic dystonia) recently reported a marked improvement in dystonia which was assessed by the Burke-Fahn-Marsden (BFM) scale. However, the reliability of this tool has rarely been evaluated and its use in a multicenter study has never been assessed prospectively. PURPOSE: To evaluate the concordance between three unblinded clinical raters and one single-blinded rater for 10 prospective series of ratings on the BFM scale in 22 dystonic patients of the SPIDY study. METHODS: Ten assessments on the BFM scale were performed under various stimulation conditions at different time points (before surgery and 1, 3, 6, and 12 months afterwards). Patients were first evaluated by three unblinded clinical raters (one per center). All assessments were videotaped and sent to a blinded rater. Intra- and inter-rater reliability was assessed using intraclass correlation coefficients. RESULTS: The intra-rater reliability at inclusion was better for the blinded rater than for the clinical raters. The inter-rater reliability (comparing the blinded rater with each clinical rater) was "very good" at inclusion, "fair" at month 1 and was "good" at month 3, month 6, and month 12. CONCLUSION: Blinding (rather than video) is probably the key factor in better intra-rater reliability and can produce more accurate rating than clinical rating. Consequently, a blind procedure should be performed systematically in multicenter studies. As inter-rater reliability is good in trained unblinded raters, the BFM scale may also be used in the follow up of dystonic patients in movement disorders centers, in clinical practice. PMID- 17274035 TI - Hemodynamic changes in the cephalic vein of patients with hemodialysis arteriovenous fistula. AB - PURPOSE: To assess via Doppler sonography the hemodynamic changes in the cephalic vein after creation of an arteriovenous fistula, and to compare radiocephalic and brachiocephalic fistulas. METHODS: Thirty-three hemodialysis patients and 54 controls were enrolled in the study. The cephalic vein was examined with a 7.5 MHz linear-array transducer. Doppler waveform parameters (resistance index, pulsatility index), time-averaged maximum flow velocity (TAV), peak systolic velocity (PSV), end-diastolic velocity (EDV), and the cross-sectional area of the vessel (A) were measured. Cephalic vein flow volume (CVFV) was calculated as TAV x A. RESULTS: CVFV, PSV, EDV, A, RI, and PI were 45.5, 7.2, 6.7, 7.7, 1.2, and 1.32 times higher, respectively, in the cephalic vein of hemodialysis patients compared with controls. Both CVFV and A were higher in brachiocephalic patients compared with radiocephalic patients (1,983 +/- 1,199 versus 870 +/- 322 ml/min [p < 0.05] and 50.3 +/- 38.9 versus 21.0 +/- 7.8 mm(2) [p < 0.05], respectively). CONCLUSION: The increase in cross-sectional area and flow volume of the cephalic vein is larger in patients with brachiocephalic fistulas than in those with radiocephalic fistulas; however, flow velocities and waveform parameters are not different. PMID- 17274036 TI - Reproducibility of 3-dimensional sonographic measurements of fetal and placental volume at gestational ages of 11-18 weeks. AB - PURPOSE: Determine the reproducibility of 3D ultrasound (3DUS) measurements of fetal and placental volumes. METHODS: We included 34 pregnant women between gestational weeks (GW) 11-18. Two operators independently acquired fetal and placental volumes using 3DUS. Each volume was acquired twice and stored on disk for off-line analysis. Intra- and interobserver reproducibility was expressed in the intra- and interclass correlation coefficient (intra-CC and inter-CC). In addition, the 3DUS volumes acquired by the first operator were calculated by the second and vice-versa to evaluate the effect of volume acquisition and caliper placement. A value >0.75 was considered a good agreement. RESULTS: Fetal and placental volume measurements were successful in 97% of all cases. Between GW 11 14 and 14-18 the median fetal volume was 20.8 (5.0-35.1) and 51.7 (37.9-132.8) ml, the median placental volume was 71.3 (40.9-111.9) and 120.7 (94.2- 273.7) ml. Bland-Altman plots were used for statistical analysis. The intraobserver reproducibility was good for fetus (intra-CC: 0.99; 0.99) and placenta (intra-CC: 0.99; 0.98). Also, interobserver reproducibility was good for fetus (inter-CC 0.98) and placenta (inter-CC 0.98). In addition, regardless of the operator who acquired the volumes, the inter-CC remained good for both fetus (inter-CC: 0.99; 0.99) and placenta (inter-CC: 0.97; 0.99). CONCLUSION: The reproducibility of fetal and placental volume measurements by 3DUS between GW 11-18 is good. In addition, individually chosen caliper placement and volume acquisition has no effect on the calculation of either volumes. PMID- 17274038 TI - Prenatal diagnosis and management of fetal pharyngeal teratoma: a case report and review of the literature. AB - We present a case of a fetal pharyngeal teratoma, which was diagnosed at 21 weeks' gestation. At the time of examination, a mass of mixed echogenicity was detected that protruded through the mouth. During a second examination 3 weeks later, the tumor had increased in size, and a severe polyhydramnios had developed. Intrauterine death of the fetus was detected at 27 weeks' gestation. Labor was induced with misoprostol, and a 1,015-g stillborn female neonate was delivered. Postmortem examination confirmed the diagnosis of a pharyngeal teratoma. PMID- 17274037 TI - Value of sonography for follow-up of mediastinal lymphadenopathy in children with tuberculosis. AB - PURPOSE: To assess the clinical value of sonography for the follow-up of mediastinal lymphadenopathy in children diagnosed with pulmonary tuberculosis (TB). METHODS: We conducted a retrospective review of the medical records of 21 children (9 boys, 12 girls) with a mean age of 6 years (range, 7.4 months to 18 years) who had a positive intradermal tuberculin skin test. All patients underwent thorough history-taking, physical examination, frontal and lateral chest radiographs, and sonographic study of the mediastinum. The mediastinum was accessed through the suprasternal and left parasternal approaches. The presence of 1 or more masses with an ovoid or round shape and hypoechoic appearance in the anterior or middle mediastinum was recorded. A comparison was made between the results of the sonographic examination of the mediastinum before administration of anti-TB agents and after 3 months of treatment. RESULTS: Pulmonary radiographic findings were suggestive of TB in 17 patients and were uncertain in 4 patients. Sonographic examination, however, detected mediastinal lymphadenopathy in all patients. A comparison of pretreatment mediastinal sonograms with those obtained after 3 months of anti-TB treatment showed a marked reduction of lymph node involvement in 17 patients (80.9%). In the remaining 4 patients, mediastinal lymphadenopathy was still present. CONCLUSION: Mediastinal sonography appears to be a valuable tool for the diagnosis of TB and in the monitoring of response to treatment in children. PMID- 17274039 TI - Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial. AB - We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline. PMID- 17274041 TI - A new home awaits the hospitalist. PMID- 17274042 TI - Which observations from the complete blood cell count predict mortality for hospitalized patients? AB - BACKGROUND: Information on the prognostic utility of the admission complete blood count (CBC) and differential count is lacking. OBJECTIVE: To identify independent predictors of mortality from the varied number and morphology of cells in the complete blood count defined as a hemogram, automated five cell differential count and manual differential count. DESIGN: Retrospective cohort study and chart review. SETTING: Wishard Memorial Hospital, a large urban primary care hospital. PATIENTS: A total of 46,522 adult inpatients admitted over 10 years to Wishard Memorial Hospital-from January 1993 through December 2002. INTERVENTION: None. MEASUREMENTS: Thirty-day mortality measured from day of admission as determined by electronic medical records and Indiana State death records. RESULTS: Controlling for age and sex, the multivariable regression model identified 3 strong independent predictors of 30-day mortality-nucleated red blood cells (NRBCs), burr cells, and absolute lymphocytosis-each of which was associated with a 3-fold increase in the risk of death within 30 days. The presence of nucleated RBCs was associated with a 30-day mortality rate of 25.5% across a range of diagnoses, excluding patients with sickle-cell disease and obstetric patients, for whom NRBCs were not associated with increased mortality. Having burr cells was associated with a mortality rate of 27.3% and was found most commonly in patients with renal or liver failure. Absolute lymphocytosis predicted poor outcome in patients with trauma and CNS injury. CONCLUSIONS: Among patients admitted to Wishard Memorial Hospital, the presence of nucleated RBCs, burr cells, or absolute lymphocytosis at admission was each independently associated with a 3-fold increase in risk of death within 30 days of admission. PMID- 17274043 TI - In-room display of day and time patient is anticipated to leave hospital: a "discharge appointment". AB - BACKGROUND: We learned from a focus group that many patients find discharge to be one of the least satisfying elements of the hospital experience. Patients cited insufficient communication about the day and time of the impending discharge as a cause of dissatisfaction. OBJECTIVE: In partnership with the Institute for Healthcare Improvement, Improvement Action Network collaborative, we tested the practicality of an in-room "discharge appointment" (DA) display. SETTING AND PATIENTS: Eight inpatient care units in 2 hospitals at an academic medical center (Mayo Clinic, Rochester, MN). INTERVENTION: DA displayed on a specially designed bedside dry-erase board. MEASUREMENTS: The primary outcome was the proportion of discharged patients who had been given a DA, including same-day DAs. Secondary outcomes were (1) the proportion of DAs scheduled before the actual dismissal day and (2) the timeliness of the actual departure compared with the DA. RESULTS: During the 4-month period, 2046 patients were discharged. Of those, 1256 patients (61%) were given a posted DA, of which 576 (46%) were scheduled at least a day in advance and 752 (60%) departed from the care unit within 30 minutes of the appointed time. CONCLUSIONS: With a program for in-room display of a DA in various hospital units, more than half the patients had a DA set, and most of the DA patients departed on time. Further investigation is needed to determine the effect of DAs on patient and provider satisfaction. PMID- 17274044 TI - Third-year medical students' evaluation of hospitalist and nonhospitalist faculty during the inpatient portion of their pediatrics clerkships. AB - BACKGROUND: Although the data on the impact of hospitalist programs on the inpatient education of medical students during their internal medicine clerkships are favorable, the data is limited on the inpatient educational experience of medical students during their pediatric clerkships. The purpose of this study was to compare the evaluations of hospitalist and nonhospitalist faculty of third year medical students during their inpatient pediatrics rotations. METHODS: We performed a retrospective study of the evaluations of third-year medical student of hospitalist and nonhospitalist faculty during their inpatient pediatrics rotations at Penn State Children's Hospital from July 1999 through September 2000. Using a 4-point scale, students gave an overall evaluation and also rated the hospitalist and nonhospitalist faculty on effectiveness as teachers, effectiveness as pediatricians, and effectiveness as student advocates. Using the same 4-point scale, students rated the following aspects of the rotation: ward rounds, sick newborn care, well newborn care, outpatient clinics, private physician's office, noon conferences, and morning report. RESULTS: A total of 67 students rotated on the pediatric inpatient service during the study period; 35 students rotated with 2 hospitalists, and 32 students rotated with 8 nonhospitalists. All 67 students (100%) submitted an evaluation. The hospitalists received higher scores than nonhospitalists on effectiveness as teachers (3.87 vs. 2.91; P < 0.001), effectiveness as pediatricians (3.94 vs. 3.25; P < .001), effectiveness as student advocates (3.76 vs. 2.97; P < .001), and in the overall evaluation (3.93 vs. 3.06; P < .001). Ward rounds were rated as more beneficial when conducted by hospitalists then when conducted by nonhospitalists (3.15 vs. 2.58; P < .006). CONCLUSIONS: Hospitalists were perceived by third-year medical students as providing more effective teaching and more satisfying overall rotations than were nonhospitalists during the inpatient portion of the students' pediatric clerkships. Further studies that examine inpatient systems, particularly as they relate to the acquisition of knowledge and the development of effective communication skills in medical learners, are needed. PMID- 17274045 TI - Pediatric hospitalist comanagement of spinal fusion surgery patients. AB - BACKGROUND: There are no published studies of hospitalist comanagement of pediatric surgical patients. OBJECTIVES: (1) To describe comanagement activities; (2) to determine the association of hospitalist comanagement with length of stay (LOS) following spinal fusion surgery. DESIGN: Retrospective analysis of the surgeons' log. SETTING: Tertiary-care pediatric hospital. PATIENTS: Patients who underwent initial spinal fusion surgery (n = 759) between July 2000 and October 2005. INTERVENTION: Hospitalist pre- and perioperative evaluation and management of medically complex patients (from December 2004 to October 2005). MEASUREMENTS: Log-transformed LOS and trend in LOS by piecewise regression were measured, adjusting for patient covariates and clustering by surgeon. RESULTS: After December 2004, 12% of all spinal fusion surgery patients (14 of 115) were comanaged by a hospitalist. Nine-three percent (13 of 14) of comanaged patients had neuromuscular scoliosis, and comanaged patients represented 37% (13 of 35) of all neuromuscular patients. Mean LOS for all spinal fusion surgeries decreased from 6.5 days (95% CI: 6.2-6.7) to 4.8 days (95% CI: 4.5-5.1) after December 2004. Mean LOS decreased more for neuromuscular patients (8.6 days [95% CI: 8.0- 9.2] to 6.2 days [95% CI: 5.5-6.9]) than for idiopathic patients (5.2 days [95% CI: 5.0-5.4] to 4.1 days [95% CI: 3.9-4.4]). Variability in LOS also decreased significantly for both groups. Prior to hospitalist comanagement, there was no change in adjusted LOS over time. After December 2004, there was a significant decline in average adjusted LOS (neuromuscular slope = -0.23 to -0.31 days/month, P = .0075; idiopathic slope = -0.10 to -0.12 days/month; P = .0007). CONCLUSIONS: The introduction of selective hospitalist comanagement of pediatric spinal fusion surgery patients was associated with significant decreases in LOS and variability in LOS. PMID- 17274046 TI - Dextran or hydroxyethyl starch in spray-freeze-dried trehalose/mannitol microparticles intended as ballistic particulate carriers for proteins. AB - The goal of this study was to clarify the effects of dextran 10 kDa on the properties of spray-freeze-dried microparticles for use with ballistic injectors. A novel carrier of trehalose, mannitol, and the polymer is known to maximize particle density. Measurements of T'(g) showed that the dextran anti-plasticizes the trehalose/mannitol, but also undergoes phase separation. The product temperature exceeded T'(g) during primary drying. The collapsed particles can therefore be explained by plastic flow of the freeze concentrate. DSC of the powder showed T(g) at 45 degrees C and, in the first scan, a wide endothermic melting peak caused by mannitol recrystallization. Catalase showed 35% activity loss on rehydration of its spray freeze-drying (SFD) powder, which was improved in the TM/D (3:3:4) formulation, but not up to that level seen with either trehalose or mannitol alone. The dextran 10 kDa, which is vital to maximize particle density, was therefore detrimental to protein integrity during SFD, as also found with a 65-72 kDa dextran. Hydroxyethyl starch (HES) 200 kDa gave similar, limited stabilizing effects on the protein. The proportion of polymer in the formulation should be low to minimize protein damage, whilst high enough to give required particle morphology and density. PMID- 17274047 TI - Prevention of wound complications following salvage laryngectomy using free vascularized tissue. AB - BACKGROUND: Total laryngectomy following radiation therapy or concurrent chemoradiation therapy is associated with unacceptably high complication rates because of wound healing difficulties. With an ever increasing reliance on organ preservation protocols as primary treatment for advanced laryngeal cancer, the surgeon must develop techniques to minimize postoperative complications in salvage laryngectomy surgery. We have developed an approach using free tissue transfer in an effort to improve tissue vascularity, reinforce the pharyngeal suture line, and minimize complications in this difficult patient population. The purpose of this study was to outline our technique and determine the effectiveness of this new approach. METHODS: We conducted a retrospective review of a prospective cohort and compared it with a historical group (surgical patients of Radiation Therapy Oncology Group (RTOG)-91-11 trial). Eligibility criteria for this study included patients undergoing salvage total laryngectomy following failed attempts at organ preservation with either high-dose radiotherapy or concurrent chemo/radiation therapy regimen. Patients were excluded if the surgical defect required a skin paddle for pharyngeal closure. The prospective cohort consisted of 14 consecutive patients (10 males, 4 females; mean age, 58 years) who underwent free tissue reinforcement of the pharyngeal suture line following total laryngectomy. The historical comparison group consisted of 27 patients in the concomitant chemoradiotherapy arm of the RTOG-91 11 trial who met the same eligibility criteria (26 males, 1 female; mean age, 57 years) but did not undergo free tissue transfer or other form of suture line reinforcement. Minimum follow-up in both groups was 12 months. RESULTS: The overall pharyngocutaneous fistula rate was similar between groups-4/14 (29%) in the flap group, compared with 8/27 (30%) in the RTOG-91-11 group. There were no major wound complications in the flap group, compared with 4 (4/27, 14.8%) in the RTOG-91-11 group. There were no major fistulas in the flap group, compared with 3/27 (11.1%) in the RTOG-91-11 group. The rate of pharyngeal stricture requiring dilation was 6/14 (42%) in the flap group, compared with 7/27 (25.9%) in the RTOG 91-11 group. In our patients, the rate of tracheoesophageal speech was 14/14 (100%), and complete oral intake was achieved in 13/14 (93%) patients. Voice Related Quality of Life Measure (V-RQOL) and Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) scores suggest that speech and swallowing functions are reasonable following free flap reinforcement. CONCLUSIONS: Free vascularized tissue reinforcement of primary pharyngeal closure in salvage laryngectomy following failed organ preservation is effective in preventing major wound complications but did not reduce the overall fistula rate. Fistulas that developed following this technique were relatively small, did not result in exposed major vessels, and were effectively treated with outpatient wound care rather than readmission to the hospital or return to operating room. Speech and swallowing results following this technique were comparable to those following total laryngectomy alone. PMID- 17274048 TI - Driving behaviors in patients with head and neck cancer during and after cancer treatment: a preliminary report. AB - BACKGROUND: The purpose of this study was to explore the driving behaviors of head and neck cancer patients during and after cancer therapy. METHODS: Eighty three patients completed a questionnaire related to driving behaviors. RESULTS: The survey revealed that 67.5% of respondents reported that they drove less or stopped driving during cancer therapy, and 26.5% continued to drive less or stopped driving after the completion of cancer therapy. Respondents typically reported greater concern about driving and relied more on other people for transportation during and after cancer therapy than before their diagnosis. Results indicated that the odds for self-restricted driving after cancer therapy were higher for those who were more concerned about driving under challenging driving situations and perceived impaired cognitive function that affected their driving ability. CONCLUSIONS: These results suggest that perceived impairment resulting from cancer therapy has a significant impact on head and neck cancer patients' driving behaviors. PMID- 17274049 TI - Survival in patients with synovial sarcoma of the head and neck: association with tumor location, size, and extension. AB - BACKGROUND: The medical literature on synovial sarcoma (SS) of the head and neck region is limited. Thus, we determined whether clinical characteristics and treatment were associated with recurrence and survival rates in patients with SS of the head and neck. METHODS: We retrospectively identified patients with a pathologic diagnosis of SS of the head and neck at our institution (a large tertiary comprehensive cancer center) and compared recurrence and survival rates by clinical characteristics and treatment. RESULTS: Forty patients with SS of the head and neck were identified from 1945 to 2004 (first case in 1968), representing <5% of all head and neck sarcomas seen at our institution during this time period. Twenty-three patients (58%) had the monophasic histologic subtype, 15 (38%) biphasic, and 2 unspecified. Most patients were male (73%), with a median age of 29 years. SS tumors were most commonly located in the neck (60%); thus, the most common symptoms were a neck mass and neck pain. No patients reported a history of radiation exposure. Higher disease-specific and overall survival rates were associated with upper aerodigestive tract location, tumors of < or =5 cm, and tumors did not extend into bone. Patients treated with surgery and adjuvant radiotherapy had higher survival and lower recurrence rates than did those treated with surgery alone or a combination of surgery, radiotherapy, and chemotherapy. This difference was not significant, and the subgroups were small, with substantial confounding by adverse prognostic factors. CONCLUSIONS: SS of the head and neck is extremely rare, and our results should be viewed with caution given the relatively small group size and treatment over a 36-year period. Survival rates were associated with tumor location, size, and extension. Treatment of SS of the head and neck should be directed toward complete surgical resection. Given the known sensitivity of SS to contemporary chemotherapy, a multimodality approach should be considered in the perioperative setting, especially in high risk patients. PMID- 17274050 TI - Speech outcomes in Cantonese patients after glossectomy. AB - BACKGROUND: We sought to determine the major factors affecting speech production of Cantonese-speaking glossectomized patients. Error pattern was analyzed. METHODS: Forty-one Cantonese-speaking subjects who had undergone glossectomy > or = 6 months previously were recruited. Speech production evaluation included (1) phonetic error analysis in nonsense syllable; (2) speech intelligibility in sentences evaluated by naive listeners; (3) overall speech intelligibility in conversation evaluated by experienced speech therapists. RESULTS: Patients receiving adjuvant radiotherapy had significantly poorer segmental and connected speech production. Total or subtotal glossectomy also resulted in poor speech outcomes. Patients having free flap reconstruction showed the best speech outcomes. Patients without lymph node metastasis had significantly better speech scores when compared with patients with lymph node metastasis. Initial consonant production had the worst scores, while vowel production was the least affected. CONCLUSION: Speech outcomes of Cantonese-speaking glossectomized patients depended on the severity of the disease. Initial consonants had the greatest effect on speech intelligibility. PMID- 17274051 TI - Metastatic carcinoma to the cervical nodes from an unknown head and neck primary site: Is there a need for neck dissection? AB - BACKGROUND: The aim of the study was to evaluate the outcomes and patterns of failure in patients with metastatic carcinoma to cervical lymph nodes from an unknown head and neck primary origin, who were treated curatively with radiotherapy, with or without neck dissection. METHODS: The study included 61 patients referred to the McGill University Hospital Centers from 1987 to 2002. The median age was 57 years, with male to female ratio of 4:1. Distribution of patients by N status was as follows: N1, 16 patients (26%); N2a, 18 (30%); N2b, 13 (22%); N2c, 7 (11%); and N3, 7 (11%). Twenty patients underwent neck dissection (11 radical, 9 functional) and 41 patients had biopsy (9 fine-needle aspiration and 32 excisional biopsy). All patients received radiotherapy. The median dose to the involved node(s) was 64 Gy, and 60 Gy to the rest of the neck. Treatment of the neck was bilateral in 50 patients (82%) and ipsilateral in 11 (18%). The minimum duration of the follow-up was 12 months, with the median of 32 months. RESULTS: The 5- and 8-year overall survival for the whole population was 79% and 67%, respectively. There was no statistically significant difference in the 8-year actuarial overall survival (64.8% and 67.6%, respectively, p = .64) and local relapse-free survival (75% vs 74.5%, respectively, p = .57), among patients who had biopsy versus those who had neck dissection. CONCLUSION: In our experience, definitive radiotherapy to the neck and the potential mucosal sites, whether preceded by neck dissection or not, is effective to achieve a good local control rate in the unknown primary cancer of the head and neck. The indication for neck dissection, in particular for early nodal stage, is controversial. PMID- 17274052 TI - Prognostic factors for Korean patients with anaplastic thyroid carcinoma. AB - BACKGROUND: Anaplastic thyroid carcinoma (ATC), although rare, is one of the most aggressive human cancers, and patients with ATC have extremely poor prognoses despite various therapeutic measures. We wished to determine the prognostic factors of survival and effect of treatment on survival rate in patients with ATC. METHODS: We retrospectively reviewed the medical records of the 121 patients (41 men and 80 women) diagnosed with ATC from January 1995 to June 2004 at 5 major referral centers in Korea. RESULTS: Mean patient age at diagnosis was 64 +/ 11 years (range, 17-84 years). Of the 121 patients, 11 (9%) had intrathyroidal tumors, 69 (57%) had extrathyroidal tumors or lymph node involvement, 29 (24%) had distant metastases, and 12 had no data about staging (9%). The mean tumor diameter was 5.5 +/- 2.5 cm (range, 0.5-17.0 cm). At a median follow-up of 41 months (range, 26-122 months), 8 patients were alive. Median survival time was 5.1 months. The disease-specific survival rates were 42% at 6 months, 16% at 12 months, and 9% at 24 months. Sixteen patients (13%) received only supportive care, 25 (21%) received surgery alone, 20 (16%) received radiation treatment or chemotherapy without surgery, and 60 (50%) received surgery plus radiation treatment or chemotherapy. Multivariate analysis showed that age less than 60 years, tumor size less than 7 cm, and lesser extent of disease were independent predictors of lower disease-specific mortality. CONCLUSIONS: Long-term survival is possible for ATC patients less than 60 years old and with small localized tumors. Although aggressive multimodal therapy, including surgery, radiation treatment, and chemotherapy, was not significantly associated with improved survival, we advocate aggressive multimodal therapy in selected ATC patients with good prognostic factors. PMID- 17274053 TI - Epidemiology of carcinogen metabolism genes and risk of squamous cell carcinoma of the head and neck. AB - The risk association between tobacco and alcohol use with squamous cell carcinoma of the head and neck (SCCHN) is well recognized. However, clearly not all individuals who smoke or drink develop SCCHN. Individual genetic susceptibility differences in carcinogen-metabolizing enzyme function, mutagen sensitivity, apoptosis, and chromosomal aberrations either alone or in combination have been theorized to modify the risk of SCCHN. Nearly all carcinogens and procarcinogens require activation by metabolizing enzymes. Similarly, detoxifying enzymes exist and deactivate carcinogens as well as their intermediate by-products. Together these enzymes are termed xenobiotic-metabolizing enzymes; genetic polymorphisms of these enzymes can modify an individual's response to carcinogens and hence the carcinogenic potential of such exposures. In this review, we explore the available evidence in recent literature regarding the risk association between SCCHN and various xenobiotic-metabolizing enzymes, including cytochrome P450s, glutathione S-transferases, N-acetyltransferases, NAD(P)H:quinone oxidoreductase 1, alcohol dehydrogenase, and aldehyde dehydrogenase. PMID- 17274054 TI - Swallowing after major surgery of the oral cavity or oropharynx: a prospective and longitudinal assessment of patients treated by microvascular soft tissue reconstruction. AB - BACKGROUND: The aim of this study was to analyze swallowing outcome in advanced oral/oropharyngeal cancer patients treated with microvascular reconstructive surgery and adjuvant radiotherapy. METHODS: Eighty patients were included. Patient, tumor, and treatment factors were assessed. Postoperative videofluoroscopic swallowing studies (VFSS) and scintigraphy tests were performed at 6 (n = 54 vs 44) and 12 (n = 32 vs 37) months. Swallowing parameters such as the oropharyngeal swallow efficiency and the Penetration/Aspiration Scale were analyzed. RESULTS: Impaired swallowing status was found at 6 months, which remained stationary at 12 months. Comorbid condition, larger tumors (T3-T4 vs T2), and resections of the base of tongue and soft palate combined (vs defects of other dynamic structures) were associated with most profound swallowing problems (p < .05). CONCLUSIONS: Swallowing difficulties are relatively frequent and can to a large extent be predicted. With the knowledge of this study, better counseling and vigilance as to swallowing difficulties may be possible. PMID- 17274055 TI - Tissue engineered prefabricated vascularized flaps. AB - BACKGROUND.: Microvascular free tissue transfer has become increasingly popular in the reconstruction of head and neck defects, but it also has its disadvantages. Tissue engineering allows the generation of neo-tissue for implantation, but these tissues are often avascular. We propose to combine tissue engineering techniques together with flap prefabrication techniques to generate a prefabricated vascularized soft tissue flap. METHODS: Human dermal fibroblasts (HDFs) labeled with fluorescein diacetate were static seeded onto polylactic-co glycolic acid-collagen (PLGA-c) mesh. Controls were plain PLGA-c mesh. The femoral artery and vein of the nude rat was ligated and used as a vascular carrier for the constructs. After 4 weeks of implantation, the constructs were assessed by gross morphology, routine histology, Masson trichrome, and cell viability determined by green fluorescence. RESULTS: All the constructs maintained their initial shape and dimensions. Angiogenesis was evident in all the constructs with neo-capillary formation within the PLGA-c mesh seen. HDFs proliferated and filled the interyarn spaces of the PLGA-c mesh, while unseeded PLGA-c mesh remained relatively acellular. Cell tracer study indicated that the seeded HDFs remained viable and closely associated to remaining PLGA-c fibers. Collagen formation was more abundant in the constructs seeded with HDFs. CONCLUSIONS: PLGA-c, enveloped by a cell sheet composed of fibroblasts, can serve as a suitable scaffold for generation of a soft tissue flap. A ligated arteriovenous pedicle can serve as a vascular carrier for the generation of a tissue engineered vascularized flap. PMID- 17274056 TI - Isolated neck recurrence after definitive radiotherapy for node-positive head and neck cancer: salvage in the dissected or undissected neck. AB - BACKGROUND: The role of salvage neck dissection for isolated regional recurrences after definitive radiotherapy (RT) is ill-defined. METHODS: Five-hundred fifty patients were treated with RT for lymph node-positive head and neck cancer. RT consisted of a median dose of 74.4 Gy. Chemotherapy was administered in 133 patients (24%). Patients were followed for neck failure after planned neck dissection (n = 341) or observation (n = 209). Salvage therapy was offered to those with isolated neck recurrences. RESULTS: There were 54 (10%) failures in the neck at a median 3.7 months after RT (range, 0 to 17 months). Thirteen patients had isolated recurrences after receiving definitive RT with (n = 11) or without (n = 2) neck dissection. Nine patients underwent attempted surgical salvage with or without re-irradiation and 4 were successfully salvaged without major complications. CONCLUSIONS: Patients with neck failure after definitive therapy usually have poor outcomes, but salvage attempts may be successful in selected patients with an isolated neck recurrence. PMID- 17274058 TI - Salivary glutathione and uric acid levels in patients with head and neck squamous cell carcinoma. AB - BACKGROUND: We evaluated the concentrations of glutathione and uric acid, low molecular weight antioxidants, in saliva of patients with head and neck squamous cell carcinoma (HNSCC), in order to identify differences with normal subjects and to obtain information about biochemical alterations of human saliva during carcinogenesis. METHODS: We compared 50 HNSCC patients, divided in 2 subsets on the basis of tumor site, with a control group of 77 subjects, without a previous diagnosis of HNSCC, matched for age, sex, alcohol consumption, and smoking status. RESULTS: At tests for equality of means by Welch and Brown-Forsythe, differences between groups resulted probable for salivary levels of glutathione (p = .004 and p < .001 respectively) but not for salivary levels of uric acid (p = .228 and p = .122 respectively). Comparing groups by Tamhane test, the patients with oral or pharyngeal cancer had significantly higher salivary levels of glutathione than both controls and patients with laryngeal cancer. CONCLUSIONS: Salivary glutathione levels may be an index of oxidative stress at the level of the upper airways and in particular of oral cavity and pharynx. Therefore, high salivary glutathione may be an epidemiological marker to identify subjects with an increased risk of developing HNSCC, to submit to strict follow-up and chemoprevention. Metabolic alterations of saliva could be both an epidemiological marker and a target for chemoprevention of oral and oropharyngeal carcinogenesis. PMID- 17274057 TI - Cyclooxygenase-2 expression in medullary thyroid carcinoma. AB - BACKGROUND: Recent studies have demonstrated that cyclooxygenase-2 (COX-2) expression is associated with the carcinogenesis of numerous neoplasms. The aim of this study was to evaluate the role of COX-2 in medullary thyroid carcinoma (MTC). METHODS: Tissue specimens of thyroid neoplasms were obtained from 22 patients with MTC and 15 control subjects with nonmalignant thyroid specimens. RESULTS: This immunohistochemical study confirms the presence of COX-2 in a significant number of MTCs. A large area of staining was noted in only 2 patients in the control group (13%) compared with 18 (82%) in the medullary carcinoma group. On a scale of 0 to 3, the average area of positive staining measured 2.35 in the study group and 0.9 in the control group (p < .0001). The average intensity of staining on a scale of 0 to 5 (deep brown) was 2.15 and 0.8 mm, respectively (p < .001). CONCLUSION: COX-2 is expressed significantly in MTC including a larger area of staining and greater intensity than in nonmalignant thyroid tissue. These findings may have important treatment implications for the use of COX-2 inhibitors in patients with MTC. PMID- 17274059 TI - Integrated PET/CT system for staging and surveillance of skull base tumors. AB - BACKGROUND: The utility of preoperative and postoperative whole body integrated positron emission tomography-computed tomography (PET-CT) scanning for staging and follow-up in patients with skull base tumors is undetermined. METHODS: We prospectively evaluated PET-CT findings in 47 patients using 57 scans. Most (35/47, 75%) had anterior skull base tumors and the majority (74%) had advanced stage (III-IV) disease. RESULTS: The scans showed high sensitivity for detection of various types of malignant tumors and provided 39 items of additional information, changing the clinical staging and management of 11 patients (23%). Recurrence of primary tumors was detected in 8 patients, positive regional (neck) metastases in 3, and distant metastases in 3. The positive uptake was due to osteoradionecrosis in 2 other patients. The sensitivity of PET-CT was 0.77 and the specificity was 0.81 (0.83 positive predictive value and 0.76 negative predictive value). CONCLUSIONS: PET-CT provides accurate data on anatomy, tumor staging, and early disease recurrence in the skull base. PMID- 17274060 TI - Fabrication of nanofibers with antimicrobial functionality used as filters: protection against bacterial contaminants. AB - A comparative study of antimicrobial activity is done using three different electrospun nanofibers namely-CA, PAN, and PVC used as control and with various amounts of AgNO(3) being treated with UV-irradiation leading to the enhancement of silver nanoparticles. DMF is used as the common solvent which helps to undergo spontaneous slow reduction at room temperature to form silver nanoparticles followed by UV-irradiation using a 400 W source. The time required for the formation of silver nanoparticles is short and they are more or less well dispersed with few such aggregates. The presence of silver nanoparticles is confirmed using various characterization techniques. The antimicrobial activity is studied using nanofibers with fabricated functionality. PMID- 17274061 TI - Efficient bioremediation of total organic carbon (TOC) in integrated aquaculture system by marine sponge Hymeniacidon perleve. AB - The aim of this study is to investigate the potential of using marine sponge Hymeniacidon perleve to remove total organic carbon (TOC) in integrated aquaculture ecosystems. In sterilized natural seawater (SNSW) with different concentrations of TOC, H. perleve removed approximately 44-61% TOC during 24 h, with retention rates of ca. 0.19-1.06 mg/h .g-fresh sponge, however no particulate selectivity was observed. The highest initial TOC concentration, in which about 2.7 g fresh sponges could remove TOC effectively in 0.5-L SNSW, is 214.3-256.9 mg/L. The highest capacity of TOC removal and clearance rate (CR) by H. perleve is ca. 25.50 mg-TOC/g-fresh sponge and 7.64 mL/h . g-fresh sponge within 24 h, respectively. Until reaching the highest TOC removal capacity, the TOC removal capacity and clearance rate of H. perleve increased with initial TOC concentration, and dropped dramatically thereafter. After reaching the highest removal capacity, H. perleve could only remove relatively lower TOC concentration in seawater in subsequent run. The TOC removal kinetics in SNSW by H. perleve fitted very well with a S-shaped curve and a Logistic model equation (R(2) = 0.999). In different volumes of SNSW with a fixed initial TOC concentration, the weight/volume ratio of sponge biomass and SFNSW was optimized at 1.46 g-fresh sponge/1-L SNSW to achieve the maximum TOC removal. When co-cultured with marine fish Fugu rubripes for 15 days, H. perleve removed TOC excreted by F. rubripes with similar retention rates of ca. 0.15 mg/h . g-fresh sponge, and the sponge biomass increased by 22.8%. PMID- 17274062 TI - Metabolic engineering of the baculovirus-expression system via inverse "shotgun" genomic analysis and RNA interference (dsRNA) increases product yield and cell longevity. AB - RNA interference (RNAi) is as powerful tool for characterizing gene function in eukaryotic organisms and cultured cell lines. Its use in metabolic engineering has been limited and few reports have targeted protein expression systems to increase yield. In this work, we examine the use of in vitro synthesized double stranded RNA (dsRNA) in the baculovirus expression vector system (BEVS), using commercially relevant cultured cells (Spodoptera frugiperda, Sf-9) and larvae (Trichoplusia ni) as hosts. First, we employed an inverse "shotgun" genomic analysis to "find" an array of 16 putative insect gene targets. We then synthesized dsRNA in vitro targeting these genes and investigated the effects of injected dsRNA on larval growth, development, and product yield. Growth and development was at times stunted and in several cases, the effects were lethal. However, dsRNA targeting an acidic juvenile hormone-suppressible protein (AJHSP1), and translational elongation factor 2 (Ef-2) resulted in significantly increased yield of model product, GFP. Next, we targeted known genes, v-cath and apoptosis inducer, sf-caspase 1, in cultured Sf-9 cells. We confirm RNAi-mediated sf-caspase 1 suppression in Sf-9 cells, but not in baculovirus-infected cells, likely due to the overriding effects of inhibitor of apoptosis protein, p35. We also demonstrate suppression of v-cath in infected cells, which leads to a approximately 3-fold increase in product yield. Overall, our results support the application of RNAi in metabolic engineering, specifically for enhancing protein productivity in the baculovirus expression vector system. PMID- 17274063 TI - Influence of calcium on microbial reduction of solid phase uranium(VI). AB - The effect of calcium on the dissolution and microbial reduction of a representative solid phase uranyl [U(VI)], sodium boltwoodite (NaUO(2)SiO(3)OH . 1.5H(2)O), was investigated to evaluate the rate-limiting step of microbial reduction of the solid phase U(VI). Microbial reduction experiments were performed in a culture of a dissimilatory metal-reducing bacterium (DMRB), Shewanella oneidensis strain MR-1, in a bicarbonate medium with lactate as electron donor at pH 6.8 buffered with PIPES. Calcium increased the rate of Na boltwoodite dissolution and U(VI) bioavailability by increasing its solubility through the formation of a ternary aqueous calcium-uranyl-carbonate species. The ternary species, however, decreased the rates of microbial reduction of aqueous U(VI). Laser-induced fluorescence spectroscopy (LIFS) and transmission electron microscopy (TEM) collectively revealed that microbial reduction of solid phase U(VI) was a sequentially coupled process of Na-boltwoodite dissolution, U(VI) aqueous speciation, and microbial reduction of dissolved U(VI) to U(IV) that accumulated on bacterial surfaces/periplasm. Under studied experimental conditions, the overall rate of microbial reduction of solid phase U(VI) was limited by U(VI) dissolution reactions in solutions without calcium and limited by microbial reduction in solutions with calcium. Generally, the overall rate of microbial reduction of solid phase U(VI) was determined by the coupling of solid phase U(VI) dissolution, U(VI) aqueous speciation, and microbial reduction of dissolved U(VI) that were all affected by calcium. PMID- 17274064 TI - Application of chromatographic theory for process characterization towards validation of an ion-exchange operation. AB - The behavior of ion-exchange chromatography is well understood with respect to changes in ionic strength, pH, resin ligand density, bed height, elution flow rate, and gradient slope. Their relative importance for any specific chromatographic situation varies. When a chromatographic operation utilized to purify a human therapeutic protein is prepared for validation before commercial production, numerous tests have to be performed to establish the relative importance of each operating parameter to define its future role and importance in the framework of in-process controls. This prioritization process is usually performed using a purely empirical approach. In this work, we demonstrate the application of a rational approach based on chromatographic theory to prioritize operating parameters. Both methodologies, empirical and rational, were performed to evaluate a specific ion-exchange chromatography operation for the preparative separation of closely related protein species. We show that the application of the rational approach has the potential to accelerate the evaluation and significantly reduce the amount of analytical testing needed. PMID- 17274065 TI - A three-dimensional computer model analysis of three hypothetical biofilm detachment mechanisms. AB - Three hypothetical mechanisms of detachment were incorporated into a three dimensional computer model of biofilm development. The model integrated processes of substrate utilization, substrate diffusion, growth, cell advection, and detachment in a cellular automata framework. The purpose of this investigation was to characterize each of the mechanisms with respect to four criteria: the resulting biofilm structure, the existence of a steady state, the propensity for sloughing events, and the dynamics during starvation. The three detachment mechanisms analyzed represented various physical and biological influences hypothesized to affect biofilm detachment. The first invoked the concept of fluid shear removing biomass that protrudes far above the surface and is therefore subjected to relatively large drag forces. The second pathway linked detachment to changes in the local availability of a nutrient. The third pathway simulated an erosive process in which individual cells are lost from the surface of a biofilm cell cluster. The detachment mechanisms demonstrated diverse behaviors with respect to the four analysis criteria. The height-dependant mechanism produced flat, steady state biofilms that lacked sloughing events. Detachment based on substrate limitation produced significant sloughing events. The resulting biofilm structures included distinct, hollow clusters separated by channels. The erosion mechanism produced neither a non-zero steady state nor sloughing events. A mechanism combining all three-detachment mechanisms produced mushroom-like structures. The dynamics of biofilm decay during starvation were distinct for each detachment mechanism. These results show that detachment is a critical determinant of biofilm structure and of the dynamics of biofilm accumulation and loss. PMID- 17274066 TI - Improving AAV vector yield in insect cells by modulating the temperature after infection. AB - Vectors based on adeno-associated viruses (AAV) are sought for therapeutic gene delivery because of their ability to transduce a variety of tissues with no significant immunological response. Production using the baculovirus expression vector (BEV)/insect cell system has the potential to meet the needs for pre clinical and clinical trials. In this co-infection system, three baculoviruses are used to produce the AAV vector. A strategy aimed at increasing encapsidation/maturation of the viral vector involved varying the temperature over the course of the process. Cultures were subjected to temperature changes at various times pre- and post-infection (up to 24 h post-infection). It was found that raising the culture temperature to 30 degrees C at the time of infection nearly tripled the infectious titer. In fact, increasing the temperature to 30 degrees C at any time in the process investigated resulted in an increase in titer. Also, raising the culture to 33 degrees C or lowering the temperature to 24 degrees or 21 degrees C resulted in lower titers. The rise in infectious titer was also confirmed by an increase in DNase resistant particles (DRPs). Varying the temperature, however, did not affect the total amount of capsids significantly. Therefore increasing the culture temperature resulted in better encapsidation as determined by the ratio of capsids to DRPs to infectious particles. It is believed that an increase in early proteins and possibly a quicker cascade of baculovirus infection events resulted in this increased packaging efficiency. PMID- 17274067 TI - Combined approach of NMR and chemometrics for screening peptones used in the cell culture medium for the production of a recombinant therapeutic protein. AB - Soy peptones or soy hydrolysates are widely used as key medium additives in serum free cell culture processes for industrial production of therapeutic recombinant proteins. The heterogeneous nature of these vegetable-derived materials can lead to substantial lot- to-lot variability in cell culture processes. In this study, we demonstrated the feasibility of nuclear magnetic resonance (NMR) spectroscopy in combination with chemometrics in rapid screening peptone lots in order to optimize efficiency and consistency of large-scale protein production. This report is the first that shows a correlation between the intrinsic NMR spectral characteristics of complex heterogeneous materials and product titer using chemometrics. PMID- 17274068 TI - Electricity generation from cellulose by rumen microorganisms in microbial fuel cells. AB - In microbial fuel cells (MFCs) bacteria generate electricity by mediating the oxidation of organic compounds and transferring the resulting electrons to an anode electrode. The objective of this study was to test the possibility of generating electricity with rumen microorganisms as biocatalysts and cellulose as the electron donor in two-compartment MFCs. The anode and cathode chambers were separated by a proton exchange membrane and graphite plates were used as electrodes. The medium in the anode chamber was inoculated with rumen microorganisms, and the catholyte in the cathode compartment was ferricyanide solution. Maximum power density reached 55 mW/m(2) (1.5 mA, 313 mV) with cellulose as the electron donor. Cellulose hydrolysis and electrode reduction were shown to support the production of current. The electrical current was sustained for over 2 months with periodic cellulose addition. Clarified rumen fluid and a soluble carbohydrate mixture, serving as the electron donors, could also sustain power output. Denaturing gradient gel electrophoresis (DGGE) of PCR amplified 16S rRNA genes revealed that the microbial communities differed when different substrates were used in the MFCs. The anode-attached and the suspended consortia were shown to be different within the same MFC. Cloning and sequencing analysis of 16S rRNA genes indicated that the most predominant bacteria in the anode-attached consortia were related to Clostridium spp., while Comamonas spp. abounded in the suspended consortia. The results demonstrated that electricity can be generated from cellulose by exploiting rumen microorganisms as biocatalysts, but both technical and biological optimization is needed to maximize power output. PMID- 17274069 TI - An in situ probe for on-line monitoring of cell density and viability on the basis of dark field microscopy in conjunction with image processing and supervised machine learning. AB - Fermentation industries would benefit from on-line monitoring of important parameters describing cell growth such as cell density and viability during fermentation processes. For this purpose, an in situ probe has been developed, which utilizes a dark field illumination unit to obtain high contrast images with an integrated CCD camera. To test the probe, brewer's yeast Saccharomyces cerevisiae is chosen as the target microorganism. Images of the yeast cells in the bioreactors are captured, processed, and analyzed automatically by means of mechatronics, image processing, and machine learning. Two support vector machine based classifiers are used for separating cells from background, and for distinguishing live from dead cells afterwards. The evaluation of the in situ experiments showed strong correlation between results obtained by the probe and those by widely accepted standard methods. Thus, the in situ probe has been proved to be a feasible device for on-line monitoring of both cell density and viability with high accuracy and stability. PMID- 17274070 TI - Correlating single cell motility with population growth dynamics for flagellated bacteria. AB - Many bacteria used for biotechnological applications are naturally motile. Their "bio-nanopropeller" driven movement allows searching for better environments in a process called chemotaxis. Since bacteria are extremely small in size compared to the bulk fluid volumes in bioreactors, single cell motility is not considered to influence bioreactor operations. However, with increasing interest in localized fluid flow inside reactors, it is important to ask whether individual motility characteristics of bacteria are important in bioreactor operations. The first step in this direction is to try to correlate single cell measurements with population data of motile bacteria in a bioreactor. Thus, we observed the motility behavior of individual bacterial cells, using video microscopy with 33 ms time resolution, as a function of population growth dynamics of batch cultures in shake flasks. While observing the motility behavior of the most intensively studied bacteria, Escherichia coli, we find that overall bacterial motility decreases with progression of the growth curve. Remarkably, this is due to a decrease in a specific motility behavior called "running". Our results not only have direct implications on biofilm formations, but also provide a new direction in bioprocess design research highlighting the role of individual bacterial cell motility as an important parameter. PMID- 17274071 TI - Butanol production from agricultural residues: Impact of degradation products on Clostridium beijerinckii growth and butanol fermentation. AB - During pretreatment and hydrolysis of fiber-rich agricultural biomass, compounds such as salts, furfural, hydroxymethyl furfural (HMF), acetic, ferulic, glucuronic, rho-coumaric acids, and phenolic compounds are produced. Clostridium beijerinckii BA101 can utilize the individual sugars present in lignocellulosic [e.g., corn fiber, distillers dry grain solubles (DDGS), etc] hydrolysates such as cellobiose, glucose, mannose, arabinose, and xylose. In these studies we investigated the effect of some of the lignocellulosic hydrolysate inhibitors associated with C. beijerinckii BA101 growth and acetone-butanol-ethanol (ABE) production. When 0.3 g/L rho-coumaric and ferulic acids were introduced into the fermentation medium, growth and ABE production by C. beijerinckii BA101 decreased significantly. Furfural and HMF are not inhibitory to C. beijerinckii BA101; rather they have stimulatory effect on the growth of the microorganism and ABE production. PMID- 17274072 TI - Identification of leptomeningeal metastasis-related proteins in cerebrospinal fluid of patients with breast cancer by a combination of MALDI-TOF, MALDI-FTICR and nanoLC-FTICR MS. AB - Leptomeningeal metastasis (LM) is a devastating complication occurring in 5% of breast cancer patients. However, the current 'gold standard' of diagnosis, namely microscopic examination of the cerebrospinal fluid (CSF), is false-negative in 25% of patients at the first lumbar puncture. In a previous study, we analyzed a set of 151 CSF samples (tryptic digests) by MALDI-TOF and detected peptide masses that were differentially expressed in breast cancer patients with LM. In the present study, we obtain for a limited number of samples exact masses for these peptides by MALDI-FTICR MS measurements. Identification of these peptides was performed by electrospray FTICR MS after separation by nano-scale LC. The database results were confirmed by targeted high mass accuracy measurements of the fragment ions in the FTICR cell. The combination of automated high-throughput MALDI-TOF measurements and analysis by FTICR MS leads to the identification of 17 peptides corresponding to 9 proteins. These include proteins that are operative in host-disease interaction, inflammation and immune defense (serotransferrin, alpha 1-antichymotrypsin, hemopexin, haptoglobin and transthyretin). Several of these proteins have been mentioned in the literature in relation to cancer. The identified proteins alpha1-antichymotrypsin and apolipoprotein E have been described in relation to Alzheimer's disease and brain cancer. PMID- 17274074 TI - From genome to proteome: back to the future. Report on the 7th Siena meeting, September 3-7, 2006. AB - This report reviews the 7th Siena Meeting 'From Genome to Proteome: Back to the Future' which took place in Italy from 3-7 September, 2006. There was a significant rise in the number of delegates attending compared with previous Siena meetings. A diversity of speakers and presentations addressed the theme of the meeting in moving proteomics forward to integrate with biology as a whole entity rather than in isolated fractions. In addition, technological advancements in sample preparation and separation as well as identification were discussed. PMID- 17274075 TI - Entering the implementation era: a report on the HUPO-PSI Fall workshop 25-27 September 2006, Washington DC, USA. AB - Since its conception in April 2002, the Human Proteome Organisation Proteomics Standards Initiative has contributed to the development of community standards for proteomics in a collaborative and very dynamic manner, resulting in the publication and increasing adoption of a number of interchange formats and controlled vocabularies. Repositories supporting these formats are being established or are already operational. In parallel with this, minimum reporting requirement have been developed and are now maturing to the point where they have been submitted for journal publication after prolonged exposure to community input via the PSI website. PMID- 17274076 TI - The glucose and nitrogen starvation response of Bacillus licheniformis. AB - The glucose and nitrogen starvation stimulons of Bacillus licheniformis were determined by transcriptome and proteome analyses. Under both starvation conditions, the main response of B. licheniformis was a switch to the usage of alternative nutrient sources. This was indicated by an induction of genes involved in the metabolism of C-2 substrates during glucose limitation. In addition, B. licheniformis seems to be using other organic substances like amino acids and lipids as carbon sources when subjected to glucose starvation. This observation is supported by the induction of a high number of genes coding for proteins involved in amino acid and lipid degradation. During nitrogen starvation, genes for several proteases and peptidases involved in nitrate and nitrite assimilation were induced, which enables this bacterium to recruit nitrogen from alternative sources. Both starvation conditions led to a down regulation of transcription of most vegetative genes, which was subsequently reflected by a reduced synthesis of the corresponding proteins. A selected set of genes was induced by both starvation conditions. Among them were yvyD, citA and the putative methylcitrate shunt genes mmgD, mmgE and yqiQ. However, both starvation conditions did not induce a general SigmaB-dependent stress response. PMID- 17274077 TI - A single-molecule-magnetic, cubane-based, triangular Co(12) supercluster. PMID- 17274078 TI - A trimetallic fulvalene-bridged dizirconocene-gallium complex. PMID- 17274079 TI - Silica immobilization of an enzyme through genetic engineering of the diatom Thalassiosira pseudonana. PMID- 17274080 TI - From PtCl(2)- and acid-catalyzed to uncatalyzed cycloisomerization of 2-propargyl anilines: access to functionalized indoles. PMID- 17274081 TI - Hierarchical self-assembly in solutions containing metal ions, ligand, and diblock copolymer. PMID- 17274082 TI - Self-assembly of periodic bicomponent wires and ribbons. PMID- 17274083 TI - Discovery of non-nucleoside inhibitors of HIV-1 reverse transcriptase competing with the nucleotide substrate. PMID- 17274084 TI - Structural basis of the activity of the microtubule-stabilizing agent epothilone a studied by NMR spectroscopy in solution. PMID- 17274085 TI - Transition-metal-catalyzed rearrangement of allenyl sulfides: a route to furan derivatives. PMID- 17274086 TI - Cationic alkyl rare-earth metal complexes bearing an ancillary bis(phosphinophenyl)amido ligand: a catalytic system for living cis-1,4 polymerization and copolymerization of isoprene and butadiene. PMID- 17274087 TI - The unexpected role of CO in C--H oxidative addition by a cationic rhodium(I) complex. PMID- 17274088 TI - Formation of C--C and C--N bonds in Ni(II) ketimide complexes via transient Ni(III) aryl imides. PMID- 17274089 TI - Redox potentiometry studies of particulate methane monooxygenase: support for a trinuclear copper cluster active site. PMID- 17274090 TI - Entrapped bonded hydrogen in a fullerene: the five-atom cluster Sc3CH in C80. AB - The synthesis and characterisation of the new endohedral cluster fullerene Sc(3)CH@C(80) is reported. The encapsulation of the first hydrocarbon cluster inside a fullerene was achieved by the arc burning method in a reactive CH(4) atmosphere. The extensive characterisation by mass spectrometry (MS), high- pressure liquid chromatography (HPLC), (45)Sc NMR, electron spin resonance (ESR), UV/Vis-NIR and Raman spectroscopy provided the experimental evidence for the caging of the five-atom Sc(3)CH cluster inside the C(80) cage isomer with icosahedral symmetry. The proposed new structure was confirmed by DFT calculations, which gave a closed shell and large energy gap structure. Thus a pyramidal Sc(3)CH cluster and the I(h)-C(80) cage were shown to be the most stable configuration for Sc(3)CH@C(80) whereas alternative structures give a smaller bonding energy as well as a smaller energy gap. PMID- 17274091 TI - Forward and backward pericyclic photochemical reactions have intermediates in common, yet cyclobutenes break the rules. AB - Photochemical pericyclic reactions are believed to proceed via a so-called pericyclic minimum on the lowest excited potential surface (S(1)), which is common to both the forward and backward reactions. Such a common intermediate has never been directly detected. The photointerconversion of 1,3-butadiene and cyclobutene is the prevailing prototype for such reactions, yet only diene ring closure proceeds with the stereospecificity that the Woodward-Hoffmann rules predict. This contrast seems to exclude a common intermediate. Using ultrafast spectroscopy, we show that the excited states of two cyclobutene/diene isomeric pairs are linked by not one, but by two common minima, p* and ct*. Starting from the diene side (cyclohepta-1,3-diene and cycloocta-1,3-diene), electrocyclic ring closure passes via the pericyclic minimum p*, whereas ct* is mainly responsible for cis-trans isomerization. Starting from the corresponding cyclobutenes (bicyclo[3.2.0]heptene-6 and bicyclo[4.2.0]octene-7), the forbidden isomer is formed from ct*. The path branches at the first (S(2)/S(1)) conical intersection towards p* and ct*. The fact that the energetically unfavorable ct* path can compete is ascribed to a dynamic effect: the momentum in C=C twist direction, acquired--such as in other olefins--in the Franck-Condon region of the cyclobutenes. PMID- 17274092 TI - Ab initio study of poly(vinyl chloride) propagation kinetics: head-to-head versus head-to-tail additions. AB - The relative importance of head-to-head versus head-to-tail additions during the free-radical polymerization of vinyl chloride is determined by ab initio methods for different chain lengths of the polymer. First, a level of theory study is performed to determine cost-effective methods for the ab initio description of the propagation kinetics of vinyl chloride. The study includes the following DFT based methods: B3LYP, B3PW91, BHandH, BHandHLYP, BLYP, BP86, MPW1K and MPW1PW91, in combination with double or triple zeta basis sets 6-31G(d) and 6-311G(d,p). Also, the more recently developed BMK and MPW1K functionals are included. The influence of diffuse functions is tested by comparison with the basis sets 6 31+G(d) and 6-311++G(3df,2p). The best-performing methods are B3LYP, B3PW91 and MPW1 K combined with the 6-31+G(d) basis set. The converged probability of head to-head propagation (2 per 1000 monomer units) is put into relation with the experimental concentrations of defect structures. A comparison is made with the head-to-head (HH) content of fluorine-substituted polymers and poly(vinyl acetate). The ab initio calculations correctly predict the relative sequence of HH content among the various polymers. PMID- 17274093 TI - Luminescence and stability of aqueous thioalkyl acid capped CdSe/ZnS quantum dots correlated to ligand ionization. AB - The spectroscopic properties of CdSe/ZnS quantum dots (QDs) were observed to change as a function of thioalkyl acid ligand. Experiments were performed using 2, 3, 6, and 11-carbon linear thioalkyl acids, as well as mercaptosuccinic acid (MSA) and dihydrolipoic acid (DHLA). Bathochromic shifts of up to 14 nm in the emission spectra of QDs capped with these ligands were observed. Similarly, hypsochromic or bathochromic shifts up to 7 nm were observed for a specific ligand in acidic or basic solution, respectively. These shifts could be correlated to the number of ionized ligands and the ability of the ligands to act as hole acceptors. It was also found that differences in quantum yield between the ligands were primarily due to variations in radiative decay rate and not nonradiative decay rate. This indicated that different degrees of QD surface passivation were not responsible for the differences, and that the radiative system must be considered as the sum of the ligands and the QD nanocrystal. The stability of QDs capped with mercaptoacetic acid, MSA, and DHLA towards aggregation at low pH was found to correlate with the pK(a) of the ligands. Spectral shifts were also observed during aggregation. Overall, the luminescence of thioalkyl acid capped QDs appears to be a complex function of dielectric constant, electrostatic or hole-acceptor interactions with ionized ligands, and, to a lesser extent, passivation. PMID- 17274094 TI - Proton conductivity study of a fuel cell membrane with nanoscale resolution. PMID- 17274095 TI - D. I. Mendeleev: reflecting on his death in 1907. PMID- 17274096 TI - LCST-type phase changes of a mixture of water and ionic liquids derived from amino acids. PMID- 17274097 TI - Detection of bis(sulfosuccinimidyl) suberate binding in electrophoresis: determination of membrane sidedness of proteins. AB - The applicability of the membrane-impermeant protein cross-linker bis(sulfosuccinimidyl) suberate (BS(3)) to the determination of membrane sidedness of proteins was tested in 3T3-L1 cells and in erythrocytes. Binding of BS(3) to proteins was apparent in electrophoresis. In three proteins of 3T3-L1 cells, protein kinase-Cepsilon, protein kinase-Czeta, and glyceraldehyde-3 phosphate dehydrogenase, BS(3) action was detectable in SDS-PAGE with immunoblotting. This enabled confirmation of the well-known intracellular localization of these proteins. In cathepsin E of erythrocytes, a mobility increase in nondenaturing PAGE was the most prominent effect of BS(3) treatment. A mechanism for the increase in mobility due to BS(3) binding is suggested. Cathepsin E was found to be located at the intracellular side of the membrane, in accordance with existing evidence. PMID- 17274098 TI - On-line automatic SPE-CE coupling for the determination of biological markers in urine. AB - Automatic SPE has been coupled on-line to CE by a transfer tube and the replenishment system of the CE instrument. The approach allows the target analytes (viz. creatinine, creatine, xanthine, hypoxanthine, uric acid, p aminohippuric acid and ascorbic acid in urine samples) to be removed from the sample matrix, cleaned up, preconcentrated and injected into the capillary. The detection limits range between 0.14 and 4.50 microg/mL, the quantification limits between 0.45 and 15.0 microg/mL, and linear dynamic ranges - which include the reference healthy human values - from the quantification limits to 1332 microg/mL. The precision, expressed as RSD, ranges between 0.38 and 2.22% for repeatability and between 1.79 and 7.61% for within-laboratory reproducibility. The errors, expressed as RSD for all compounds, range between 0.20 and 6.90%. The time for automatic SPE and that necessary for the individual separation-detection of the target analytes are 13 and 12 min, respectively; the analysis frequency is 5 h(-1). The accuracy of the method and potential matrix effects were studied by using spiked samples and recoveries between 96.00 and 103.07 % were obtained. The proposed method was applied to samples from healthy young students. PMID- 17274099 TI - Open tubular CE for in vitro oxidation studies of human very-low-density lipoprotein particles. AB - Human very-low-density lipoprotein (VLDL) particles were immobilised on the inner wall of electrochromatographic fused-silica capillaries, and the applicability of these capillary columns in oxidation studies was investigated. Capillaries coated with radiolabelled VLDL particles showed a coating efficiency of 97%, and allowed estimation of the amount of VLDL present in a capillary. Radioactivity measurements and atomic force microscopy with tapping mode confirmed the presence of VLDL particles as a monolayer. The pI determined for the VLDL was 4.7-4.8 varying with the human source. The effects of VLDL concentration, coating time and pH on the coating stability were clarified, and the stability was examined in terms of the repeatability of EOF and retention factors of selected steroids. The repeatability of run-to-run and the coating-to-coating reproducibility ranged from 2.6 to 4.9% and 3.2 to 6.6%, respectively. The lifetime of a coating was at least 7 days or 84 consecutive runs. The in situ copper-mediated VLDL oxidation carried out in the capillary with optimised VLDL coating showed that, during the oxidation of VLDL particles, the negative charges of the particles are increased, leading to enhanced EOF mobilities. Several oxidation parameters, including copper sulfate concentration, amount of EDTA needed to stop the reaction, pH and the oxidation procedure, were examined. Effect of the oxidation process on the stability of the coating in one capillary, and in five different capillaries ranged between 0.4-4.1% and 0.8-6.6%, respectively. The in situ oxidation of VLDL particles was compared with that of low-density lipoproteins. PMID- 17274100 TI - Dynamic coating using methylcellulose and polysorbate 20 for nondenaturing electrophoresis of proteins on plastic microchips. AB - A dynamic coating using methylcellulose (MC) and a nonionic detergent (polysorbate 20) was developed, which controlled protein adsorption onto the surface of microchannels on a microchip made of poly(methyl methacrylate) (PMMA). Optimum concentration of polysorbate 20 in combination with the range of MC concentrations controlled the protein adsorption onto the microchannel surface, and increased the solubility of the protein samples while facilitating the injection of high concentrations of MC solutions into the microchannels. Higher concentrations of nonionic detergent increased the EOF mobility as opposed to the electrophoretic mobility and caused the electrophoresis to fail. Nondenaturing microchip electrophoresis of protein samples with molecular masses ranging from 20 to 100 kDa were completed in 100 s. Also, successful separation of a BSA sample and its complex with anti-BSA mAb ( 220 kDa) was achieved on a PMMA microchip. The separation exhibited high reproducibility in both migration time (RSD = 1%) and peak area (RSD = 10-15%). PMID- 17274101 TI - Assignment of human plasma polypeptides on a nondenaturing 2-D gel using MALDI-MS and PMF and comparisons with the results of intact protein mapping. AB - Human plasma proteins were separated by 2-DE under nondenaturing conditions followed by the assignment of the CBB-stained spots using MALDI-MS and PMF, aiming to correlate the information of intact proteins with that of constituent polypeptides. A microgel system was employed to facilitate the analysis. Totally 157 spots on a nondenaturing micro-2-DE gel were numbered, the spots were excised, the proteins in the gel pieces were subjected to in-gel digestion with trypsin followed by polypeptide analysis using MALDI-MS and PMF. Two PMF algorithms, MASCOT (with Swiss-Prot database) and ProFound (with NCBInr database) were employed. A total of 153 spots out of the 157 provided significant match (p <0.05) with polypeptides in databases. Eighty spots were assigned to contain multiple (2-4) polypeptides, suggesting (i) noncovalent interaction between proteins/polypeptides, (ii) disulfide bonding of polypeptides, or (iii) overlapping of the protein locations on the gel. The results of polypeptide assignment coincided very well with the results of protein mapping previously reported, in which 33 plasma proteins were identified using blotting immunochemical staining (Manabe, T., Takahashi, Y., Higuchi, N., Okuyama, T., Electrophoresis 1985, 6, 462-467). Further, 19 polypeptides in 25 spots were newly assigned. These results demonstrate that the techniques of MALDI-MS and PMF can be applied for analysis of proteins separated on nondenaturing 2-DE gels, providing information on their polypeptide structure. The integrated information on proteins and polypeptides would help the comprehensive understanding on the functions of complex protein systems. PMID- 17274102 TI - Mass distribution, polydispersity and focusing properties of carrier ampholytes for IEF. III: pH 2.5-4 intervals. AB - To study the molecular mass distribution and number of species in narrow-range (2 pH-unit wide, in the nominal pI 2-4 or 3-5 interval) carrier ampholytes from four commercial sources (Bio-Lyte, Servalyt, Ampholine and Pharmalyte), a 2-D technique was adopted, consisting of a preparative focusing step in a Rotofor instrument, followed by analysis of every other collected fraction (10 out of 20) by CE-MS. It was found that Ampholine pH 3.5-5 contains 105 different molecular mass (M(r)) compounds, in the M(r) interval 205-965 Da, for a total of 446 isoforms. Bio-Lyte pH 3-5 consists of 84 different M(r) species, in the M(r) range 216-965 Da, for a total of 383 isoforms. Servalyt pH 2-4 is made of 227 different M(r) compounds, in the M(r) interval 204-929 Da, for a total of 1201 isoforms. Pharmalyte pH 2.5-5 comprises 245 amphoteres, in the M(r) range 203-857 Da, for a total of 857 isoforms. Pharmalyte appears to be the best brand, with the vast majority of species focusing sharply at their pI position and almost no 'poor' species, distributed along the entire pH gradient, denoting an extremely shallow pH/mobility curve across the pI value. Due to some overlap with the adjacent acidic pH 4-6 interval, the species in common have been evaluated: the most extended overlaps are found in Ampholine (55% of the species appearing in the two neighbouring intervals) and in Servalyt (47% coincidence). The lowest overlaps are found in Pharmalyte (23%) and in Bio-Lyte (20%). PMID- 17274103 TI - The use of 3D rendering, VCI-C, 3D power Doppler and B-flow in the evaluation of interstitial pregnancy with arteriovenous malformation treated by selective uterine artery embolization. AB - Cornual pregnancy is a rare form of ectopic pregnancy. We describe a case of cornual pregnancy suspected by two-dimensional ultrasonography (2DUS) and confirmed by three-dimensional volume contrast imaging in the C-plane. Three dimensional power Doppler showed a particularly rich blood supply and two dimensional color Doppler mapping demonstrated arteriovenous malformation (AVM). The feeding vessel originating from the right uterine artery and AVM were demonstrated with B-flow spatio-temporal image correlation (STIC) modality. Conservative management was chosen to preserve the uterus. Angiography confirmed the diagnosis of AVM; embolization with polyvinyl alcohol particles and embolization coils was performed through the right uterine artery until occlusion of the AVM and feeding vessels had occurred. Postprocedure color Doppler mapping and B-flow STIC modalities demonstrated absence of flow in the AVM. Serum human chorionic gonadotropin (hCG) levels gradually fell to non-pregnant levels during the ensuing 5 weeks. To the best of our knowledge this is the first report of cornual pregnancy with AVM. We demonstrate here the value of new three dimensional ultrasound modalities in the diagnosis of cornual pregnancy and the use of embolization as an effective therapeutic option when conservative treatment with uterine preservation is desired. PMID- 17274104 TI - Large calcifications in ovaries otherwise normal on ultrasound. AB - OBJECTIVE: To evaluate calcifications >or= 5 mm in length in ovaries that are otherwise normal on ultrasound, and to determine whether such large ovarian calcifications are an indicator of ovarian neoplasm. METHODS: This was a retrospective study reviewing pelvic ultrasound results at our unit between October 1994 and April 2002 to identify patients with ovarian calcifications that were >or= 5 mm in maximum length in otherwise normal ovaries, and who also had follow-up imaging studies. Patient medical histories were reviewed, calcification characteristics, including number, size, shape and laterality of calcifications, were recorded and follow-up imaging studies were reviewed to assess change in size of the calcification and to see if a neoplasm had developed. RESULTS: The study group consisted of 28 patients. The mean length of imaging follow-up was 35.2 +/- 30.7 months. The mean size of the calcifications was 7.4 +/- 2.3 (range, 5-13) mm. The calcification remained stable in all 28 patients and no ovarian neoplasms developed in any of the patients. Histological confirmation was available in one patient and this revealed dystrophic calcification in a corpus albicans. CONCLUSION: Calcifications ranging from 5 to 13 mm in length in otherwise normal ovaries remain stable on follow-up imaging and are not an indicator of current or future ovarian neoplasm. Published by John Wiley & Sons, Ltd. PMID- 17274105 TI - In vivo magnetic resonance spectroscopy of transgenic mouse models with altered high-energy phosphoryl transfer metabolism. AB - Studies of transgenic mice provide powerful means to investigate the in vivo biological significance of gene products. Mice with an under- or overexpression of enzymes involved in high-energy phosphoryl transfer (approximately P) are particulary attractive for in vivo MR spectroscopy studies as the substrates of these enzymes are metabolites that are visible in MR spectra. This review provides a brief overview of the strategies used for generation and study of genetically altered mice and introduces the reader to some practical aspects of in vivo MRS studies on mice. The major part of the paper reviews results of in vivo MRS studies on transgenic mice with alterations in the expression of enzymes involved in approximately P metabolism, such as creatine kinase, adenylate kinase and guanidinoacetate methyl transferase. The particular metabolic consequences of these enzyme deficiencies in skeletal muscle, brain, heart and liver are addressed. Additionally, the use of approximately P systems as markers of gene expression by MRS, such as after viral transduction of genes, is described. Finally, a compilation of tissue levels of metabolites in skeletal muscle, heart and brain of wild-type and transgenic mice, as determined by in vivo MRS, is given. During the last decade, transgenic MRS studies have contributed significantly to our understanding of the physiological role of phosphotransfer enzymes, and to the view that these enzymes together build a much larger metabolic energy network that is highly versatile and can dynamically adapt to intrinsic genotoxic and extrinsic physiological challenges. PMID- 17274106 TI - Regional velopharyngeal compliance in the rat: influence of tongue muscle contraction. AB - The velopharynx is the most collapsible segment of the upper airway in patients with obstructive sleep apnea. However, we do not know if velopharyngeal compliance is uniform throughout its length, or if compliance is modified by contraction of upper airway muscles. We tested the hypothesis that rostral and caudal velopharyngeal (VP) compliance differs, and that tongue muscle contraction reduces compliance. High-resolution MR images of the VP were made at nasopharyngeal pressures ranging from -9 to 9 cmH(2)O in anesthetized rats. Images were obtained twice at each pressure, once with and once without bilateral hypoglossal nerve stimulation. The volume of the caudal and rostral VP was computed at each pressure. The caudal VP was significantly (P = 0.0058) more compliant than the rostral VP, but electrical stimulation of the tongue muscles did not change compliance. VP critical pressure (Pcrit; pressure at zero airway volume) averaged -25.2 and -12.1 cmH(2)O in the rostral and caudal VP, respectively (P < 0.0001). Coactivation of tongue protrudor and retractor muscles or contraction of protrudor muscles alone dilated the VP and made Pcrit more negative (P < 0.0001), but only in the caudal VP. In the rat, the caudal VP is more collapsible than the rostral VP, and either coactivation of tongue protrudor and retractor muscles or contraction of protrudor muscles alone makes this region more difficult to close. Thus, tongue muscle contraction protects the caudal VP, which appears to be a particularly vulnerable segment of the nasopharyngeal airway. With suitable modification, the methods described here, including tongue muscle stimulation at different pharyngeal pressures, may be appropriate for experiments in human subjects. PMID- 17274107 TI - Illness stories on the internet: what do breast cancer patients want at the end of treatment? AB - The study aims to elicit user requirements for internet-based applications disclosing fellow patients' illness stories for the benefit of breast cancer patients. Twenty-six breast cancer patients, recruited via the Dutch Patient Organization for Breast Cancer, were interviewed about their preferences with regards to content, appearance, and search options concerning fellow patients' illness stories online. The interviews were analysed quantitatively (SPSS) and qualitatively (NVivo). Participants were mainly interested in fellow patients' experiences about how to cope with emotions, the impact of cancer in daily life, and physical discomforts. Most participants preferred a section of an illness story in text format about a specific topic; some of them wanted to be able to click on to the corresponding complete story, comprising of text alone or supported by voice or video clip. A majority of participants wanted to be able to select illness stories on the basis of several authors' features, i.e. treatment underwent, age, presence of metastases, time since diagnosis, and whether or not caring for children. Participants gave arguments for their preferences. The findings of this study will be used for designing an online trial with breast cancer patients aiming at refining the user requirements. PMID- 17274108 TI - Abstracts of the American Society for Therapeutic Radiology and Oncology 48th Annual Meeting, November 5-9, 2006, Philadelphia, Pennsylvania, USA. PMID- 17274109 TI - Abstracts of the 28th International Congress of Clinical Neurophysiology, 10-14 September 2006, Edinburgh, Scotland. PMID- 17274111 TI - Abstracts of the 8th International Conference of Neuroimmunology, October 2006. PMID- 17274110 TI - Abstracts of the 70th Annual Meeting of the American College of Rheumatology and the 41st Annual Meeting of the Association of Rheumatology Health Professionals, November 10-15, 2006, Washington, DC, USA. PMID- 17274113 TI - Effect of ramipril on the incidence of diabetes. PMID- 17274112 TI - CD4+ Th1 cells promote CD8+ Tc1 cell survival, memory response, tumor localization and therapy by targeted delivery of interleukin 2 via acquired pMHC I complexes. AB - The cooperative role of CD4+ helper T (Th) cells has been reported for CD8+ cytotoxic T (Tc) cells in tumor eradication. However, its molecular mechanisms have not been well elucidated. We have recently demonstrated that CD4+ Th cells can acquire major histocompatibility complex/peptide I (pMHC I) complexes and costimulatory molecules by dendritic cell (DC) activation, and further stimulate naive CD8+ T cell proliferation and activation. In this study, we used CD4+ Th1 and CD8+ Tc1 cells derived from ovalbumin (OVA)-specific T cell receptor (TCR) transgenic OT II and OT I mice to study CD4+ Th1 cell's help effects on active CD8+ Tc1 cells and the molecular mechanisms involved in CD8+ Tc1-cell immunotherapy of OVA-expressing EG7 tumors. Our data showed that CD4+ Th1 cells with acquired pMHC I by OVA-pulsed DC (DCOVA) stimulation are capable of prolonging survival and reducing apoptosis formation of active CD8+ Tc1 cells in vitro, and promoting CD8+ Tc1 cell tumor localization and memory responses in vivo by 3-folds. A combined adoptive T-cell therapy of CD8+ Tc1 with CD4+ Th1 cells resulted in regression of well-established EG7 tumors (5 mm in diameter) in all 10/10 mice. The CD4+ Th1's help effect is mediated via the helper cytokine IL 2 specifically targeted to CD8+ Tc1 cells in vivo by acquired pMHC I complexes. Taken together, these results will have important implications for designing adoptive T-cell immunotherapy protocols in treatment of solid tumors. PMID- 17274114 TI - Case 32-2006: a girl with fever after a visit to Africa. PMID- 17274115 TI - Case 32-2006: a girl with fever after a visit to Africa. PMID- 17274116 TI - Parietal representations for hand-object interactions. PMID- 17274118 TI - Abstracts from the XVIIIth Congress of the European Association for Cranio Maxillofacial Surgery, 12-15 September 2006, Barcelona, Spain. PMID- 17274117 TI - Mad fly disease. PMID- 17274119 TI - Interdisciplinary transport phenomena in microgravity and space sciences IV. Proceedings of a conference. August 7-12, 2005. Tomar, Portugal. PMID- 17274120 TI - Proceedings of the 2004 Cooper Institute Conference. PMID- 17274121 TI - [Abstracts of the German Pain Congress, Berlin, Germany, 11-14 October 2006]. PMID- 17274122 TI - Prosthetic cardiac valve prices 'stable'. PMID- 17274123 TI - Infective endocarditis presenting as a splenic laceration. PMID- 17274124 TI - WHO, UNAIDS set course for HIV testing. PMID- 17274125 TI - Funding. Congress reauthorizes CARE Act in last moments of session. PMID- 17274126 TI - ADA. Hospital board granted immunity in denial of HIV care. PMID- 17274127 TI - Drug advertising. AHF: Viagra ads encouraging nonmedical use could fuel HIV spread. PMID- 17274129 TI - Insurance. Company must pay denied HIV medical bills twice. PMID- 17274128 TI - Prevention. Studies: circumcision reduces risk of contracting HIV. PMID- 17274130 TI - Prison. Extended segregation justified for volatile inmate with AIDS. PMID- 17274131 TI - ADA. Baker's HIV-discrimination claim survives dismissal. PMID- 17274133 TI - Program innovation. Innovative HIV chat program gets grant. PMID- 17274132 TI - State Department urged to end HIV discrimination. PMID- 17274134 TI - Attitudes toward HIV. Study: many Americans indifferent to HIV/AIDS. PMID- 17274135 TI - Medicaid provider trumps physician over HIV wasting drug. PMID- 17274136 TI - United Nations: HIV/AIDS pandemic spreading faster. PMID- 17274138 TI - Woman awarded $978,000 over exposure to HIV. PMID- 17274137 TI - Harassment. Teacher's dismissal affirmed over proselytizing to students. PMID- 17274139 TI - Medicare. HIV/AIDS doctor's conviction for health care fraud affirmed. PMID- 17274140 TI - National HIV/AIDS leadership awards debut. PMID- 17274141 TI - Antiretroviral suppression of HIV in the context of persistently low CD4 counts: new insights. PMID- 17274142 TI - Policy watch. Stop AIDS, keep the promise. PMID- 17274143 TI - Hepatitis C update. PMID- 17274144 TI - Images in HIV/AIDS. Parotid gland enlargement and fat maldistribution syndrome in an HIV-infected man. PMID- 17274145 TI - Challenges to the elimination of mother-to-child transmission of HIV infection: four case reports. AB - HIV can be transmitted from an infected mother to her child during pregnancy or labor and postnatally through breast milk. Nearly 25 years after the first documented case of HIV infection, the decrease in perinatal HIV infections in the United States represents a major success in public health. Despite this achievement, several challenges remain in the effort to eliminate mother-to-child transmission of HIV infection. In the state of Nevada, the number of perinatally acquired HIV infections decreased to its lowest in 2003, with only 1 infected infant, compared with the peak in 1998 of 8 infected infants. We report 4 cases of mother-to-child HIV transmission that occurred in Las Vegas between October 2005 and June 2006 and that highlight some of the challenges in reducing the incidence of perinatal infections. A comprehensive, multidisciplinary program that allows for expanded access to prenatal care, rapid HIV testing in labor and delivery for women of unknown HIV serostatus, and close follow-up of exposed infants must be present to sustain the achievements made in the reduction of mother-to-child transmission of HIV infection. PMID- 17274146 TI - Editorial comment: within our reach--the end of perinatal HIV transmission. PMID- 17274147 TI - Seven steps to better adherence: a practical approach to promoting adherence to antiretroviral therapy. AB - The introduction of effective antiretroviral therapy has resulted in dramatic clinical benefits for those persons who have access to it. Adherence to such therapy has emerged as both the major determinant and the Achilles' heel of this success. Many patients have levels of adherence too low for durable virologic control. Virologic failure from suboptimal adherence diminishes the potential for long-term clinical success, leads to the emergence of drug-resistant virus, and may undermine the dramatic benefits in health parameters seen in resource-rich countries and expected in developing countries as effective antiretroviral therapy becomes more widely available. While adherence to antiretroviral therapy is regarded as the most important determinant of clinical outcomes in HIV positive persons, most clinicians receive little guidance on practical steps to support and improve adherence. A structured, evidence-based, 7-step approach to supporting and improving antiretroviral adherence is described here. These steps can serve as a starting point or review for care providers working to support HIV positive patients to successfully adhere to antiretroviral therapy. PMID- 17274148 TI - [Public health administration in late- 19th-century England, with special reference to the activities of Brighton Sanitary Authority]. PMID- 17274149 TI - Outbreak news. Meningococcal disease, Uganda. PMID- 17274150 TI - Intercountry meningitis meeting: preparing for the next epidemic seasons, Mali, October 2006. PMID- 17274151 TI - Diagnosis: Fulminant hepatic failure--etiology most likely hepatitis A. PMID- 17274153 TI - "May the married be single, and the single happy": Blackwood's, the maga for the single man. PMID- 17274152 TI - Diagnosis: Lead toxicity without acute encephalopathy. PMID- 17274154 TI - Gentlemanly politeness and manly simplicity in Victorian England. PMID- 17274155 TI - [Anthropology as legimating science: on the connection of racial theory and racial politics in the biography of Italian eugenicist Guido Landra, 1939-49]. PMID- 17274156 TI - Incidence and effects of West Nile virus infection in vaccinated and unvaccinated horses in California. AB - A prospective cohort study was used to estimate the incidence of West Nile virus (WNV) infection in a group of unvaccinated horses (n = 37) in California and compare the effects of natural WNV infection in these unvaccinated horses to a group of co-mingled vaccinated horses (n = 155). Horses initially were vaccinated with either inactivated whole virus (n = 87) or canarypox recombinant (n = 68) WNV vaccines during 2003 or 2004, prior to emergence of WNV in the region. Unvaccinated horses were serologically tested for antibodies to WNV by microsphere immunoassay incorporating recombinant WNV E protein (rE MIA) in December 2003, December 2004, and every two months thereafter until November 2005. Clinical neurologic disease attributable to WNV infection (West Nile disease (WND)) developed in 2 (5.4%) of 37 unvaccinated horses and in 0 of 155 vaccinated horses. One affected horse died. Twenty one (67.7%) of 31 unvaccinated horses that were seronegative to WNV in December, 2004 seroconverted to WNV before the end of the study in November, 2005. Findings from the study indicate that currently-available commercial vaccines are effective in preventing WND and their use is financially justified because clinical disease only occurred in unvaccinated horses and the mean cost of each clinical case of WND was approximately 45 times the cost of a 2-dose WNV vaccination program. PMID- 17274157 TI - Effect of nematophagous fungus Duddingtonia flagrans and energy supplementation on the epidemiology of naturally infected kids. AB - Gastrointestinal (GI) nematode infection is a major constraint for grazing livestock production. The increasing prevalence and severity of anthelmintic resistant nematodes in many parts of the world has led to a search for non chemical control options. Under experimental conditions, the nematophagous fungus Duddingtonia flagrans is emerging as an alternative to chemotherapy for the control of GI nematode infection in biological production systems. Also, recent information points to the role of energy nutrition to increase the immune response against GI nematode infection. In this study the effect of D. flagrans and energy supplementation on the epidemiology of GI nematode infections is explored on grazing kids. Four groups of 10, 4-month old goats were turned out on infected pasture in the early spring and allocated to four separate paddocks where they were rotationally grazed for 16 weeks. One of these groups (F) received 0.5 x 10(6) D. flagrans spores/kg BW/d. Another group (S) was supplemented with 100 g barley grain per day. A third group (F+S) received both nematophagous fungi and barley supplement treatments simultaneously while the fourth group (C) was used as a non-treated control. Both nematophagous fungi and barley supplement had a significant effect (P<0.01) on reducing pasture infectivity, faecal egg excretion and worm burdens at slaughter that was particularly evident for Trichostrongylus colubriformis. The combination of both treatments showed a synergistic effect on the control of gastrointestinal nematode infections. At slaughter, the average total post-mortem worm count of the F+S group was reduced by 65% compared with the non-treated control. The results herein show that D. flagrans can act as an efficient biological control agent against kid GI nematode infections on pasture, which could further improve carcass characteristics. While small amounts of energy supplement can also reduce kid infection, the effect of D. flagrans as a biological control agent appeared clearly enhanced both in magnitude and duration by energy supplementation. This has clear implications for grazing animals and provides an efficient method for the practical control of parasitic nematodes in biological production systems. PMID- 17274158 TI - The JECH gallery. Money orders and alcohol yes; fruits, vegetables and skimmed milk no. PMID- 17274159 TI - [Medicine and teaching in Galen's Ars medica]. PMID- 17274160 TI - [Galen's Ars medica: is it authentic?]. PMID- 17274161 TI - [Leisure and literary creation in the home of Galen]. PMID- 17274163 TI - [On the Hippocratic concept of health and sickness]. PMID- 17274162 TI - [Defense and illustration of Classical Humanism: a presentation on a project towards an edition of Galen in the collections of the University of Paris]. PMID- 17274164 TI - [Traces of Hippocratic medicine in two late Roman tracts: Polybus of Kos]. PMID- 17274165 TI - [Growing old and being old in antiquity]. PMID- 17274166 TI - The William Nelson ECG Quiz: familial hypokalaemic paralysis. PMID- 17274167 TI - Trial by media: professor Marie Cassidy: Doolin lecture 2006. PMID- 17274168 TI - Mental health. PMID- 17274169 TI - Tinea capitis in a paediatric population. AB - Tinea capitis is an increasing problem in Europe. The pattern of infection is changing with an increase in pathogenic anthropophilic dermatophytes particularly Trichophyton tonsurans. We aimed to determine the frequency of tinea capitis in a paediatric population attending dermatology outpatients and examine the clinical spectrum of disease. A retrospective analysis was performed of all laboratory proven tinea capitis cases presenting to the dermatology outpatient department at The Children's University Hospital, Temple Street over an 18-month period (1st January 2004 to 30th of June 2005 inclusive). Sixty-two children had tinea capitis of whom 53 (85.5%) were of African descent. Thirty-five (56%) were male and 27 female (44%). The average age at presentation was 4.02 years (age range 1 163 months) with five cases occurring in children less than one year of age. The most common pathogen was the anthropophilic dermatophyte Trichophyton tonsurans, accounting for 47 (75.8%) of all cases of tinea capitis. Eight (12.9%) were secondary to Microsporum ferrigineum, 2 (3.2%) secondary to Trichophyton violaceum, both Trichophyton soudanese and Trichophyton verruosum accounted for 1.6% each. The zoophilic organism Microsporum canis was diagnosed in 3 cases (4.8%). Presenting signs included scaling of the scalp (35.47%), scaling of the scalp and alopecia (53.24%), and alopecia and kerion (11.29%/o). The duration of symptoms was recorded in 52 patients with the average duration 8.38 months (range 0.5-72 months). In 20 cases an associated skin involvement on other areas of the body was recorded. All patients at diagnosis were either on no, suboptimal or inappropriate treatment. The prevalence of tinea capitis is increasing in this hospital based cohort. The main pathogen is now Trichophyton tonsurans. Children of African descent are at increased risk of infection. The diagnosis is poorly recognized and needs to be highlighted as a public health issue. There is a need for community based prevalence studies. PMID- 17274170 TI - The prevalence of antiphospholipid antibody syndrome among systemic lupus erythematosus patients. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by excess autoantibody production. It typically affects women of childbearing age. Antiphospholipid antibody syndrome (APLAs) is associated with serious co morbidity to mother and child characterized by recurrent vascular thrombosis and/or pregnancy associated morbidity. We reviewed SLE patients attending a specialist connective tissue disease clinic both to assess the occurrence of APLAs and its clinical presentations and to audit the effectiveness of screening for APL antibodies in a specialist clinic. 204 patients attended the newly established connective tissue disease outpatient clinic over a twenty-seven month period; 42 (34 female, 8 male) with a diagnosis of SLE. Ten patients (24%), eight female and 2 male with a median age of 38.5 years (range 20 to 64 years) fulfilled the ACR criteria for secondary APLAs (Table 2). The commonest clinical presentation was pulmonary embolus (five patients). Overall 37 patients (88%) with SLE were screened for APLAs during the study period: 94% of females and 62.5% of males were screened (for anticardiolipin antibodies, lupus anticoagulant or both), 27% had evidence of APLAs, 24% had positive antibodies but were asymptomatic. There is a significant occurrence of APLAs among SLE patients. Given the important clinical implications of this disorder including substantial risk of fetal loss and patient morbidity or mortality, routine screening of all SLE patients for APL antibodies is recommended. PMID- 17274171 TI - Laparoscopic appendectomy versus open appendectomy in children. AB - This study compares the benefits, advantages and complications of laparoscopic Appendicectomy (LA) versus Open Appendectomy (OA) in children's in Dublin Ireland. Total 200 patients were studied. Hundred of LA and 100 for OA. Out of 100 LA 58 were male, 42 were female aged between 4-15 yr. and out of 100 OA 58 were male, 42 were female aged between 4-14 yr. The mean operative time of LA was 35.8 minutes and the Anaesthetic time was 46.6 minutes. Patients having LA had less post-op pain with early start of feed at 16.7 hrs, and had significantly less post-op hospital stay of 1.6 days. Post op complications rate was 3%. The patient started the normal life activities at 10.8th post op day. Wound infection rate was 3% with Re-admission rate of 2%. The mean operative time of OA was 45.66 minutes and the Anaesthetic time was 56.75 minutes. Patients having OA had post op pain hospital stay of 2.55 days with start of feed at 24.7 hrs. Post op complications rate was 2%. The patient started the normal life activities at 15.78th post op day. Wound infection rate was 3% with Re-admission rate of 1%. Laparoscopic appendectomy is safe alternative to conventional open appendectomy, leading to early ambulation, decreased hospital stay, and better exploration of abdominal cavity. PMID- 17274173 TI - Submandibular gland stones, a clinical review. AB - The purpose of this study is to highlight the role of per-oral extraction of submandibular calculi in the management of salivary sialadenitis. This study was based on a retrospective review of patients presenting with submandibular sialadenitis over a 5-year period. 26 patients presented with a history of sialadenitis, with a palpable stone in the floor of the mouth and were considered candidates for surgery. 21 (80%) underwent per-oral extraction using marsupialization of the duct to maintain duct patency. 4 (15%) were deemed unsuitable when assessed under general anaesthesia due to inaccessible calculi. 2 (9%) of the 21 patients that underwent per-oral extraction required gland excision, due to persistence of symptoms. The remaining 19 (91%) are symptom free with a mean follow-up of 18 months. There were no neurological post-operative sequelae in the group. 1 patient had no surgical intervention at the end. In conclusion, per-oral extraction of submandibular salivary calculi is a safe method of relieving symptoms due to sialadenitis in patients with palpable accessible calculi in the floor of the mouth. PMID- 17274172 TI - Stroke unit care is superior to general rehabilitation unit care. AB - Robust evidence exists for the efficacy of stroke units in improving stroke outcome. To date no Irish and little international data exist comparing stroke unit and general rehabilitation unit care. 207 patients admitted to a stroke unit (136--65.7%) and a general rehabilitation unit (71--34%) in the Mid-Western region from September 2000-August 2002 were included in the study. There was no difference in patient age, gender or admission criteria between the units. The stroke unit was associated with a shorter length of stay (mean 21 versus 33 days, p < 0.01) and a higher rate of home discharge (50% versus 38%, p < 0.01). Patient survival at discharge (86% versus 70.4%, p < 0.01), 3 months (84.5% versus. 69.5%, p < 0.01) and 6 months (81% versus. 66%, p < 0.01) post-admission was better among stroke unit patients. PMID- 17274175 TI - The cost of treating type 2 diabetes (CODEIRE). AB - Diabetes mellitus is the most common chronic metabolic disease and a major source of morbidity and mortality. Type 2 diabetes (T2D) is by far the most prevalent form of diabetes accounting for around 90% of cases worldwide. In recent years it has become apparent that a diabetes epidemic is unfolding as a result of increasing obesity, sedentary lifestyles and an ageing population. The enormity of the diabetes epidemic raises concern about the total cost to healthcare systems. This study was undertaken to investigate the direct healthcare costs of managing T2D in Ireland. Data was captured on 701 diabetes patients attending four diabetes centres. A bottom-up, prevalence-based design was used, which collected data on hospital resource use and clinical outcome measures over a 12 month period (1999/2000). The study was observational in nature, focusing on usual care of patients with T2D. Although the true prevalence of T2D in Ireland is unknown, conservative estimates are 3.9% for diagnosed diabetes and 6% for both diagnosed and undiagnosed diabetes. Using these figures the annual total direct cost was estimated at 377.2 million euro for diagnosed diabetes and 580.2 million euro for both diagnosed and undiagnosed diabetes. This corresponds to 4.1% and 6.4% of total healthcare expenditure respectively. Hospitalisations were the main driver of costs, accounting for almost half of overall costs, while ambulatory and drug costs accounted for 27% and 25% respectively. Hospitalisation costs were high because 60% of patients had developed complications. The most common microvascular and macrovascular complications were neuropathy and angina respectively. The annual cost of care for patients with microvascular and macrovascular complications were 1.8 and 2.9 times the cost of treating those without clinical evidence of complications respectively. The figure for patients with both types of complications was 3.8. This study shows that T2D is a very costly disease, largely due to the cost of and the management of complications. Many diabetes related complications are preventable, therefore it would appear a cost-effective approach for government to invest in the prevention of T2D and diabetes related complications. PMID- 17274174 TI - Detection rates of sexual dysfunction amongst patients with multiple sclerosis in an outpatient setting--can this be improved? AB - Sexual dysfunction is an important, yet under-reported symptom in multiple sclerosis (MS). AIMS: To assess detection rates of sexual dysfunction in a MS clinic, and whether a patient-completed questionnaire could improve detection. A retrospective chart review of ninety-eight patients with MS was performed, to compare the frequency of documented discussions regarding sexual function before and after using a questionnaire of symptoms. 6 of 98 patients (6.1%) had documented reference to sexual function in chart review. Of the 90 patients who completed the questionnaire, 30 (33%) had sexual dysfunction--a significant difference in detection rates. There is an association between sexual dysfunction and the prevalence of urinary dysfunction. Fewer patients were asked about sexual dysfunction than urinary or bowel dysfunction. There is a relatively low detection rate of sexual disorders in patients with MS attending outpatient clinics, which may be improved by a patient-completed questionnaire. PMID- 17274176 TI - Early onset of colonic adenocarcinoma associated with cystic fibrosis--a case report. AB - We report the case of the onset of colorectal adenocarcinoma occurring in an 18 year-old patient, suffering from Cystic Fibrosis. This represents a presentation of colon cancer at an earlier stage than previously reported. Despite this, there is an established link between the two diseases although the pathogenesis is, as yet, unknown. This early onset emphasizes yet another association with the disease and encourages clinicians to be aware of potentially disastrous complications. PMID- 17274177 TI - Oral ulceration--the importance of biopsy. AB - Pemphigus vulgaris is a rare cause of oral ulceration. A 34 year old male presented with a three week history of severe oral ulceration which was initially treated as aphthous ulceration. However, he failed to improve and a mucosal biopsy was performed. Histology and immunostaining confirmed pemphigus vulgaris. PMID- 17274178 TI - Sudeck atrophy. AB - This paper reviews the contribution of Sudeck to the understanding of the condition commonly referred to as 'Sudeck's atrophy' and which is commonly used as a synonym for a condition variously called reflex sympathetic dystrophy, causalgia, algodystrophy and others. Sudeck came to show in his later papers that the so-called atrophy was, in the majority of cases, a normal inflammatory process of bone change in the course of healing after an inflammatory/infective or traumatic insult. Contrary to the views of much current literature, the vast majority of such cases had a good prognosis. In those cases which became pathological and had a correspondingly poorer prognosis, the characteristic clinical picture becomes associated with radiological and pathological changes, which, uniquely, are described by Sudeck. A knowledge of such radiological and pathological substrate for clinical symptomatology is important in the analysis of pain following trauma. PMID- 17274179 TI - White-coat effect or more than that! PMID- 17274180 TI - Neurobiological effects of microwave exposure: a review focused on morphological findings in experimental animals. AB - The possible risk of electromagnetic radiation (EMR) for nervous system is regularly published from the middle of 20th century. Numbers of neurobiological studies demonstrate that various EMR frequencies induce changes in nervous tissue of experimental animals but the evidence for health effect of EMR to the nervous system remains uncertain. To solve the fundamental questions about possible health hazard of modern technologies, the main producers of EMR, further intensive experimental studies on animals are needed. This review, focused on morphological findings achieved in various experimental animals, demonstrates that blood-brain barrier is the most studied morpho-functional unit of CNS in experiments with EMR. The morphological findings in experimental animals, in many cases controversial, put some evidence on nervous tissue structural damage after the EMR exposure. In spite of numerous literary data a wide range of contemporary neuro-morphological methods waits to be utilized in the EMR experimental paradigm. Using these methods could play an important role in answering the question about possible adverse effects of microwaves on nervous system. PMID- 17274182 TI - Hypnotizability and spatial attentional functions. AB - Many theories of hypnotic responding have proposed that differences in hypnotic trait rely on differences in frontal attentional functions. Evidence of hypnotizability-related attentional abilities are, however, very scant. This study was designed to investigate the relationship between hypnotizability and executive control components of attention in the spatial domain. We chose the Attention Network Test that enables to analyze alerting, orienting and executive control functions by measuring reaction times (RTs) to targets cued for different locations in space. According to Posner theory, alerting, orienting and executive control effects were found in both groups. No differences between highly susceptible (Highs) and low susceptible individuals (Lows) on executive control functions were found. However, in Highs alerting was significantly smaller than in Lows and Highs were significantly faster than Lows in the no and central cue conditions. These findings suggest that Highs would be endowed with a basal higher efficiency in achieving and maintaining their readiness to respond to incoming stimuli. This relation between hypnotizability and alerting, is discussed in terms of a possible more efficient noradrenergic activity driven by frontal attentional systems. PMID- 17274181 TI - REM sleep related increase in brain temperature: a physiologic problem. AB - The roles of metabolic heat production, arterial blood flow and temperature in the genesis of the brain temperature increase related to REM sleep occurrence in several mammalian species are discussed on the basis of available experimental evidence. The experimental data show that only changes in arterial blood flow and temperature consistently underlie the rise in brain temperature in presence (cat) or absence (rabbit) of the carotid rete. The alteration of cardiovascular regulation in REM sleep is the remote cause of such rise. The proximate causes are decrease in carotid blood supply and increase in vertebral blood supply to the brain and related depression of systemic and selective brain cooling. PMID- 17274183 TI - The "all-or-none" law in skeletal muscle and nerve fibres. AB - In 1905 the Cambridge physiologist Keith Lucas extended the "all-or-none" principle (introduced by H. P. Bowditch for the cardiac tissue) to skeletal muscle and nerve fibres. Nevertheless, in a short time it was clear that nerve fibres obey this law, but also that frequency of discharge is another relevant factor in the nervous conduction. PMID- 17274184 TI - Contribution of REM sleep to Fos and FRA expression in the vestibular nuclei of rat leading to vestibular adaptation during the STS-90 Neurolab Mission. AB - 1. Electrophysical studies performed in ground-based experiments have shown that VN neurons respond to labyrinthine signals following stimulation of macular gravity receptors. Additional evidence indicates that VN neurons may also respond to extralabyrinthine signals of pontine origin, which occur during the PGO waves typical of REM sleep (Bizzi et al., 1964a, b; cf. also Pompeiano, 1967, 1970, 1974 for ref.). 2. In a previous study (Pompeiano et al., 2002) changes in Fos and FRA expression were used to identify the short-term (Fos) and the long-term (FRA) molecular changes which affect the VN neurons at different time points of the space flight. In particular, while Fos protein persists in the brain tissue only for a few hours (6-8 hrs) after its induction, FRA proteins, which can also be induced in the same experimental conditions, persist in the brain tissue for longer periods of time (i.e. from 12/24 hrs to days). 3. In order to relate the changes in gene expression which occurred in the VN during the space flight either to gravity changes or to REM sleep, we investigated in a recent study (Centini et al, 2006) the changes in Fos and FRA expression which occurred in different phases of the sleep-waking cycle, thus being indicative of the animal state. We could then compare the results obtained during the space lab Mission with those previously observed either in ground-based experiments during the physiological state of waking and slow-wave (SWS) or during neurochemically induced episodes of PS, as obtained after microinjection of appropriate agents in dorsal pontine structures of rats. 4. Our findings indicated that a waking state possibly associated with episodes of SWS, occurred at FD2 and FD14, i.e. at launch and after exposure of the animal to microgravity. It appeared also that at the reentry (R + 1) rather than at launch (FD2), an increase in Fos and FRA expression affected the noradrenergic LC neurons, as well as several related structures. These findings probably resulted from the acceleration stress, or immobilization stress as shown by the appearance of a starle reaction (or arrest reaction) which occurred after landing. This condition of stress was followed after landing by an increase in Fos and FRA expression which affected ventromedial medullary reticular structures, whose descending projections are involved in the suppression of postural activity during PS. Moreover, their ascending projections were likely to increase the FRA expression in the neocortex as well as in several regions of the limbic system, such as the dentate gyrus and the hippocampus, which lead to EEG desynchronization and the theta activity during PS. FRA expression affected also at the reentry pontine and diencephalic structures, such as the lateral parabrachial nucleus and the central nucleus of the amygdala, which are known to contribute to the occurrence of pontine waves and the related bursts of REM. 5. Observations made on the various components of the vestibular complex indicated that no Fos and FRA expression occurred in the LVN at the four different mission time points. However, an increase in Fos and FRA expression occurred particularly in the medial (MVN) and spinal vestibular nuclei (SpVN) at FD2 and at R + 1, i.e. 1 day after launch and 12-24 hours after landing, respectively. The pattern of FRA expression observed in the VN during the space flight was generally similar to that of Fos, except at the reentry, when FRA positive cells were observed throughout the whole SpVN, but not the MVN, which showed only a few labeled cells in its rostral part. In contrast to this finding, a prominent Fos expression was found not only in the SpVN, but also throughout the entire MVN. In this case the Fos labeling affected not only the caudal but also the rostral part of this structure, including the dorsal (MVePc) rather than the ventral aspect (MVeMc). Grounded on their different time of persistence, both Fos and FRA expression which occurred in the SpVe could be attributed to the increase in gravity force experienced during take-off and landing, while the Fos pattern which affected particularly the MVN soon after the reentry could additionally be attributed to the rebound episode of PS following the forced period of waking which occurred after landing and after the prolonged (12 days) exposure to microgravity. 6. The results of the present experiments provide the first molecular evidence that pontine activity sources producing rhythmic discharges of vestibulo-ocular neurons during REM sleep may substitute for labyrinthine signals after prolonged (12 days) exposure to microgravity, thus contributing to activity-related plastic changes in the VN leading to readaptation of the vestibular system to 1 G. PMID- 17274185 TI - [Clinical effectiveness and safety of paroxetine in post-stroke depression: results from a phase 4, open label, multicenter clinical trial with 26 weeks of follow-up]. AB - INTRODUCTION: Prevalence of post-stroke depression ranges from 20% to 50%. Treatment of depression positively correlated with the success of rehabilitation, quality of life, and the post-stroke patient's independence. AIM: The primary goal of the study was to establish the therapeutic efficacy of paroxetine (measured by the changes of Hamilton Depression Scale Score) in post-stroke depression. Secondary outcomes were changes in clinical status (based on Clinical Global Impression), alterations of mental capabilities (by Mini-Mental State Examination) and changes in quality of life (based on Quality of Life values). METHOD: An estimation of the efficacy of paroxetine treatment of 788 patients with post-stroke depression (Hamilton Depression Scale Score > 18) was performed in an open-label phase IV multicenter trial, during a clinical (8 weeks) as well as a follow-up period (a total of 26 weeks). The applied doses of paroxetine were: 20, 30 or 40 mg per day, subject to their therapeutic effect. RESULTS: On the third week of the study (i.e.: at the 2nd visit) the mean Hamilton Depression Scale Score decreased significantly to 12.3 points; from a starting mean basic score of 24.8 points. At the conclusion of the clinical phase (by the end of the 8th week) we found an Hamilton Depression Scale Score of 8.6 points, which decreased further to 6.6 points by the end of the follow-up period (i.e.: the 26th week). At the end of the 3rd week 92% of the patients stated that paroxetine was effective while this number grew to 93.1% by the end the 8th week. Events related to secondary outcomes also showed significant improvements of similar size: by the end of the 8th week the clinical status of 92.8% of the patients improved (in 81.3% by a remarkable rate); mental output of the patients (based on Mini-Mental State Examination) grew significantly from a starting score of 26.7 to 27.9 and their Quality of Life values grew from 204 points to 238 points by the end of the 8th week and by the end of the 26th week it reached to 251 points; another indication of a significant improvement of their quality of life. In the course of the study 8.21% of the patients experienced side effects; the most frequent of these were: nausea/vomiting, dizziness, headaches and diarrhea. Serious adverse events occurred in 1.9% of the patients during the 26 weeks period of the study although these were unrelated to the taking of paroxetine. In the course of the study the patients' compliance was clearly good: by the end of the 8th week 94%, at the end of the 26th week 90.7% of them reported for control visitation, in other words, during the 6 months study their dropout rate was less than 10%. CONCLUSION: the selective serotonin-reuptake inhibitor paroxetine effectively improved the symptoms of depression, the functional and cognitive performance, as well as the quality of life of patients with post-stroke depression. The drug was safe and well tolerable. PMID- 17274186 TI - [Life-threatening dermatoses]. AB - In the present review an overview from a special angle of dermatologic practice is provided: dermatologic diseases that represent immediate danger for the patients' life. Diseases were included in this circle on the basis of their importance in general medical practice. This selection includes diseases from dermatologic oncology, pustular and erythrodermic forms of psoriasis, bacterial, allergic conditions, and STDs. Severe burns, autoimmune bullous skin diseases and classic immunologic conditions are also covered. Beside the general approach, novel therapeutic possibilities are discussed in significant details. PMID- 17274187 TI - [Genetics in patients with psoriatic arthritis]. AB - OBJECTIVES: HLA antigens were studied in 100 Hungarian patients suffered from psoriatic arthritis. Genetic markers for the development of different clinical pattern of the disease and skin disorder were identified. METHODS: Determination of class I and class II antigens was performed by using microlymphocytotoxicity assay. RESULTS: The frequency of HLA-Cw6, HLA-B16 (and its split B-39) and HLA B27 antigens were significantly higher in psoriatic arthritis patients than in the Hungarian general population. No connection was found between HLA-DR4, DR7, B17 antigens and psoriatic arthritis. The patients were classified according to the subgroups proposed by Gladman. The comparisons between the clinical subgroups revealed a significant association of HLA-B27 with spondylitis (Gladman 4, 5, 6, 7). There was no association between HLA DR4 and polyarticular pattern of the disease (Gladman 3, 7). Psoriasis seemed to be significantly associated only with HLA-Cw6. There was a higher frequency of HLA-B38 in psoriatic arthritis patients with erythroderma. PMID- 17274188 TI - [Balloon dilatation of cervical anastomosis stricture after subtotal resection of the esophagus]. AB - AIMS: The stricture of the anastomosis is one of the most common complications of the subtotal esophageal resections. The authors present indications, technics and results of the endoscopic dilatation. PATIENTS AND METHODS: In a 10 year period 26 patients (22 male, 4 female, mean age of 53.7 years) with stricture of anastomosis between the esophagus and the neo-esophagus after subtotal esophageal resection were dilated endoscopically 82 times. The indication of the resection was tumour in 23 (88.5%) cases, congenital atresia in 2 (7.7%) cases and corrosive disease in one (3.8%) case. In 7 (31.8%) cases the stricture developed after anastomosis leakage. The mean time between the operation and the dilatation was 7.8 months. The cause of the stricture was cancer recurrency in 4 (15.4%) cases. RESULTS: There were no complications related to the dilatation. The mean number of the dilatation was 3.2 (1-9). There was no significant difference between the number of dilatation in patients with or without previously anastomotic leakage. The success rate of the dilatation for benign strictures was 95.5%. In only one patient (4.5%) was needed operative intervention. In the 4 patients with tumour recurrency a stent was also implanted in the stenosis. CONCLUSIONS: The endoscopic dilatation for the treatment of the cervical anastomosis stricture after subtotal esophageal resection is a successful method with a low rate of complications. In cases of tumour recurrency a stent implantation is suggested. PMID- 17274189 TI - [Bela Issekutz was born 120 years ago]. PMID- 17274190 TI - [Fifty years at the 2nd Department of Ophthalmology]. PMID- 17274191 TI - WHO Expert Committee on Biological Standardization. AB - This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international recommendations for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the attention of the Committee and provides information on the status and development of reference materials for various antibodies, antigens, blood products and related substances, cytokines, growth factors, and endocrinological substances. The second part of the report, of particular relevance to manufacturers and national regulatory authorities, contains guidelines on the production and quality control of candidate tetravalent dengue virus vaccines and recommendations for the preparation, characterization and establishment of international and other biological reference standards. Also included are a list of recommendations, guidelines and other documents for biological substances used in medicine, and of international standards and reference reagent for biological substances. PMID- 17274195 TI - 4 nurse attorneys tell you how to stay out of legal hot water. PMID- 17274197 TI - Life after joint replacement surgery. PMID- 17274196 TI - Joint surgery: paving the way a smooth recovery. PMID- 17274199 TI - Hands-on help. Hot and cold packs. PMID- 17274198 TI - Part 2. JCAHO's Patient Safety Goals: preventing med errors. PMID- 17274200 TI - Get real! You have rights! PMID- 17274201 TI - Racial influences associated with weight-related beliefs in African American and Caucasian women. AB - This study examines African American and Caucasian women's perception of how race affects their weight. Structured focus groups that used the nominal group technique (NGT) were conducted with four groups of African American women (n = 30) and four groups of Caucasian women (n = 30). Participants generated responses to the question, "How does being a Black/White woman affect your weight?" The African American groups generated 48 unique ideas, including unhealthy food preparation, poor food selection habits, lack of exercise, stress, increased risk of chronic diseases, and associated medical costs; the Caucasian groups produced 32 responses, including distorted expectations of perfect body type, success depended on thinness and beauty, social pressures, media, and men's preferences. Results suggest that the African American women focused on food choices and health consequences while the Caucasian women emphasized body size and aesthetics. The observed differences support a need for culturally specific interventions that promote good eating patterns and healthy body shapes. PMID- 17274203 TI - Obesity and pulmonary function in Navajo and Hopi children. AB - BACKGROUND: Although several reports have shown an adverse cardiovascular and metabolic risk profile associated with childhood obesity, few reports have examined the effects of childhood obesity on pulmonary function. OBJECTIVE: The purpose of this study was to examine the influence of obesity on pulmonary function in Navajo and Hopi children. METHODS: Subjects included 256 (110 males, 146 females) Hopi children 6-12 years of age and 557 (274 males, 283 females) Navajo children 6-12 years of age (N = 813). The body mass index was used to classify subjects as normal weight, overweight, or obese on the basis of international reference values. Forced vital capacity (FVC), forced expired volume in one second (FEV1), FEV1% (FEV1 to FVC ratio; FEV1/FVC), and forced expiratory flow between 25%-75% of vital capacity (FEF25-75) were determined according to the American Thoracic Society recommendations. RESULTS: Approximately 26% of Navajo and Hopi children were defined as overweight additional 16% (14.6% of boys and 17.7% of girls) were defined as obese. In general, the patterns showed an increase in pulmonary function between normal weight and overweight children and a decrease in pulmonary function of obese children. Significant differences among groups existed for FEV1% and FEF25-75 in boys and FVC and FEV1 in girls. CONCLUSIONS: The results indicate the pulmonary consequences of obesity in children and provide further evidence of the adverse consequences of pediatric obesity among Native Americans. PMID- 17274202 TI - An inverse association between calcium and adiposity in women with high fat and calcium intakes. AB - OBJECTIVES: To assess the association between calcium intake and body composition in African Black and White women. DESIGN: Cross-sectional survey. SETTING: Metabolic unit. PARTICIPANTS: A convenience sample of 106 White and 102 Black healthy urban women, 20-50 years old, stratified for body mass index (BMI). MAIN OUTCOME MEASURES: Dietary calcium intake, fat intake, BMI, percentage body fat, fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT), blood pressure. METHODS: After an overnight fast, weight, height and blood pressure were measured, subjects underwent a 75-g OGTT, and blood samples were taken. Food frequency questionnaires were completed, and body composition was measured by anthropometry and air displacement plethysmography. RESULTS: Mean calcium and fat intakes were significantly higher in White women (1053.8 mg/day and 103.1 g/day, respectively) than in the Black women (523 mg/day and 69.2 g/day), resulting in higher calcium:fat-intake ratio in White women. After adjustment for age and total energy intake, significant negative correlations were found between calcium intake and fasting insulin (r = -.337, P = .01) and HOMA-IR (r = -.334, P = .01) in the White subjects. The calcium:fat ratio correlated negatively with BMI (r = .328, P < .012), percentage body fat (r = -.336, P = .01), fasting insulin (r = .374, P = .004), postprandial insulin (r = -.328, P = .01), and HOMA-IR (r = .365, P = .005). In the Black subjects, a significant negative correlation was found between calcium intake and blood pressure. CONCLUSION: The association between calcium intake and percentage body fat, BMI, fasting glucose, and insulin were significant only with high intake of fat and calcium, which is not characteristic of the habitual diet of African women. PMID- 17274205 TI - Childhood obesity among Head Start enrollees in southeastern Minnesota: prevalence and risk factors. AB - BACKGROUND: Up to 32% of US Head Start enrollees in inner-city settings have been reported to be obese. However, little is known about the prevalence of overweight and associated risk factors in Head Start enrollees in non-inner-city settings. OBJECTIVES: To determine the prevalence of childhood obesity from 1998 to 2001 and associated risk factors for overweight among Head Start enrollees in southeast Minnesota. METHODS: The study was designed as a cross-sectional study. Subjects were 788 children ages three to five years who were enrolled in Head Start of Olmsted and Freeborn Counties, Minnesota, between 1998 and 2001. Anthropometric data and other sociodemographic variables were collected. The Centers for Disease Control and Prevention (CDC) classification for body mass index (BMI) was used (ie, overweight is > 95th percentile BMI for age). Data were fit to a logistic regression model to identify risk factors associated with overweight. RESULTS: From 1998 to 2001, the overall prevalence of overweight and at risk for overweight was 12.9% and 12.2%, respectively. The prevalence of overweight from 1998 to 2001 remained steady, but the prevalence of at risk doubled from 8.2% in 1998 to 16.1% in 2001. On the basis of BMI at the time of enrollment in Head Start, Mexican origin (OR = 2.76; P = .002) and speaking English as a second language (ESL) at home (OR = 1.75; P = .026) were independent predictors for overweight. CONCLUSIONS: The Head Start setting in a nonurban area does not confer any more or less risk for overweight for enrollees, compared to those in urban settings. Children within a certain ethnic group (eg, Mexican) and those who speak English as a second language at home have a higher risk of being overweight. Specific early interventions for these children in a Head Start setting are warranted. PMID- 17274204 TI - Relations of changes in exercise self-efficacy, physical self-concept, and body satisfaction with weight changes in obese white and African American women initiating a physical activity program. AB - OBJECTIVE: To determine the effectiveness of changes in factors associated with self-efficacy theory for predicting weight change in obese women of two ethnic groups. DESIGN: Obese (body mass index [BMI] > or = 30 kg/m2) White (n = 34) and African American (n = 30) women (mean age 44 years) were assessed on measures of body satisfaction, self-efficacy, and weight change over 20 weeks. SETTING: Community wellness centers. INTERVENTION: A supported exercise and nutrition information treatment. MAIN OUTCOME MEASURES: Changes in Body Areas Satisfaction Scale (BAS), Physical Self-Concept Scale (PSCS), and Exercise Self-Efficacy Scale (ESES) scores and changes in body weight over 20 weeks. RESULTS: Significant improvements were found on measures of exercise self-efficacy, body satisfaction, and weight, with a trend (P = .073) toward significantly greater mean weight loss by the White group (-15.5 kg vs -9.1 kg). Linear multiple regression analyses, with simultaneous entry of changes in BAS, PSCS, and ESES scores, significantly predicted changes in weight for both the White (R2 = .25) and African American (R2 = .50) group. The primary predictor of weight change for the White group was change in BAS scores (beta = -.42) and for the African American group was change in ESES scores (beta = -.68). CONCLUSIONS: Self-efficacy theory was supported as an explanatory model for both groups, with notable differences. Implications for weight loss intervention design and application are discussed. PMID- 17274206 TI - Ascribing meaning to hypertension: a qualitative study among African Americans with uncontrolled hypertension. AB - OBJECTIVE: The objective was to elicit patients' perceptions regarding the meaning of hypertension and to identify the personal, social, and environmental factors that might influence their perceptions. DESIGN: Qualitative study. SETTING: Adult ambulatory care practice PARTICIPANTS: African American patients with uncontrolled hypertension. INTERVENTION/METHODS: In-depth structured interviews were conducted with a purposive sample of 60 patients. Interviews were audiotaped, transcribed verbatim, and analyzed by using grounded theory. RESULTS: Patient descriptions of hypertension were grouped into three categories: 1) their thoughts on hypertension; 2) the consequences of hypertension; and 3) the impact that having hypertension had on their lifestyle. Factors that might have shaped how patients described hypertension were grouped into three categories: 1) the experiences of their social networks such as family and friends; 2) their personal experiences; and 3) information about hypertension that they might have gathered from the medical literature or during an encounter with a healthcare provider. Patients with family members who had experienced hypertension-related complications such as stroke were more likely to view hypertension as a serious condition. Patients who themselves experienced hypertension-related symptoms and who also had family members with a history of hypertensive disease were more likely to describe a willingness to make lifestyle changes. CONCLUSIONS: In this study, personal experiences, experiences of family and friends, and encounters with the healthcare environment influenced patients' perceptions of hypertension and their willingness to make lifestyle changes. These findings can be used as a framework for helping to tailor effective and culture-specific interventions. PMID- 17274207 TI - Prevalence of the metabolic syndrome among US middle-aged and older adults with and without diabetes--a preliminary analysis of the NHANES 1999-2002 data. AB - OBJECTIVE: This study examined the racial differences in the distribution of the individual and clustered metabolic syndrome components among diabetics and nondiabetics and the presence of inflammatory markers. STUDY DESIGN AND METHOD: This is a secondary data analysis of the National Health and Nutrition Examination Survey (NHANES) from 1999-2002. The analysis only included adults aged > or = 40 years who were White, Black, and Mexican American. Differences in the rate of metabolic syndrome, each of its components, and inflammation markers among the three racial groups were examined by using chi-square tests. RESULTS: An estimated 12 million adults > or = 40 years of age have diagnosed and undiagnosed diabetes. Most diabetics have metabolic syndrome (69.9% for Whites, 64.8% for Blacks, and 62.4% for Mexican Americans). Abdominal obesity is more prevalent among Whites with diabetes than Mexican Americans (80.6% vs 67.8%, P = .008). Hypertension is significantly greater among Blacks with diabetes (73.1%) as compared to Whites (58.6%) and Mexican Americans (50.8%); hypertension in those without diabetes was 47.5% among Blacks, 32.4% among Whites, and 23.4% among Mexican Americans. Among nondiabetics, Blacks have higher prevalence of elevated serum C-reactive protein (17.4%) and high plasma fibrinogen (49.7%) than Whites (9.7% and 36%, respectively). CONCLUSION: These data demonstrate racial differences in the prevalence of components of the metabolic syndrome among diabetics and nondiabetics. They raise questions about the current definition of the metabolic syndrome, which weights each component equally. Further research is necessary to more precisely quantify the characteristics of metabolic syndrome in different racial and ethnic groups. PMID- 17274208 TI - Black-white differences in age trajectories of hypertension prevalence among adult women and men, 1999-2002. AB - OBJECTIVES: To describe age patterns of hypertension prevalence in young through middle-aged adults and to test the hypothesis that hypertension prevalence rises more rapidly with age among Blacks than Whites in the United States. DESIGN, SETTING, AND PARTICIPANTS: Using multiple logistics regression, we predicted probability of being hypertensive for participants ages 15-65 years in the National Health and Nutrition Examination Survey (NHANES) IV, 1999-2002. We estimated age-specific Black-to-White odds ratios of hypertension overall, by sex, and adjusted for body mass index (BMI) and poverty income ratio. We also followed NHANES cohorts to test whether differential age patterns of hypertension prevalence by race or gender represented cohort effects. MAIN OUTCOME MEASURE: Hypertension: systolic blood pressure > or = 140 mm Hg, diastolic blood pressure > or = 90 mm Hg, or current antihypertensive medication use. RESULTS: Black/White odds of hypertension increased from 1.71 to 3.12 between ages 15 and 65. Odds for women increased faster, from 2.11 to 4.04. By age 40, Black women had the highest hypertension rates and steepest age-gradient of race/sex groups. Adjustment for poverty income ratio did not affect results. Adjustment for BMI reduced Black women's hypertension risk somewhat but not men's. Cohort analysis confirmed a more rapid increase in hypertension prevalence among Blacks and women. CONCLUSIONS: Hypertension screening of Blacks should begin at young ages. Early diagnosis and vigilant management are critical to addressing racial and sex differences and their effect on cardiovascular disease, life expectancy, and maternal and infant health. Psychosocial stressors merit consideration as candidates for primary prevention. Addressing fundamental causes is needed. Understanding the growing age-gradient increase among US Black women is pressing. PMID- 17274209 TI - Prevention of hypertension and diabetes in an urban setting in South Africa: participatory action research with community health workers. AB - The project aimed to identify factors that contribute to hypertension and diabetes and to design and implement appropriate local interventions to prevent these noncommunicable diseases and promote healthy lifestyles. This was a community-based participatory action research project in which researchers and community health workers (CHWs) were the main participants. The triple A approach to planning interventions was used, that is, the process of assessing the situation, analyzing the findings, and taking action based on this analysis. Both qualitative and quantitative methods were employed. Twenty-two CHWs working in site C, Khayelitsha, a deprived urban area of Cape Town, South Africa, participated in the study. Findings from the situational assessment indicated a lack of knowledge among CHWs and the community about hypertension and diabetes and the risk factors for these non-communicable diseases. Economic constraints and cultural beliefs and practices influenced the community's food choices and participation in physical activity. On the basis of these findings, a training program was proposed that would provide CHWs with the skills to prevent hypertension and diabetes in their community. A program was developed and piloted by the project team. A health club that focuses on promoting healthy lifestyles is currently being piloted. This paper illustrates the unique involvement of CHWs in a successful participatory action research project on the prevention of hypertension and diabetes and promotion of health in a deprived urban setting. The project emphasizes the importance of involving local people in community based initiatives to promote health and identifies that the primary role of health services is to develop appropriate skills in the local community, monitor activities, and facilitate a link with primary health services. PMID- 17274210 TI - Aerobic exercise improves cardiorespiratory fitness but does not reduce blood pressure in prehypertensive African American women. AB - OBJECTIVE: To determine the effectiveness of a 10-week aerobic exercise training intervention on blood pressure, cardiorespiratory fitness, and workload in African American women with prehypertension. DESIGN: After we obtained informed consent and medical clearance, each participant underwent baseline measurements, an aerobic exercise-training regimen, and postintervention assessments. SETTING: This investigation took place in Columbus, Ohio, on the campus of The Ohio State University. PARTICIPANTS: Twelve sedentary African American women with prehypertension volunteered to participate. INTERVENTIONS: Study participants trained three days per week for 30 minutes per session at an intensity of 70% maximal oxygen consumption (VO2 peak) for 10 weeks. MAIN OUTCOME MEASURES: Blood pressure, cardiorespiratory fitness, and workload achieved. RESULTS: Exercise training resulted in a significant improvement in cardiorespiratory fitness and workload capacity. However, no significant reductions in blood pressure were seen after the 10-week aerobic exercise period. CONCLUSIONS: Ten weeks of 30 minutes of aerobic exercise, three times a week at 70% VO2 peak, is a sufficient stimulus to improve cardiorespiratory fitness and workload achieved. However, this exercise regimen was not adequate in eliciting a simultaneous reduction in systolic, diastolic, or mean arterial blood pressure in this cohort of prehypertensive African American women. Additional studies are needed to determine specific exercise protocols that would be effective in lowering blood pressure in various populations. These exercise protocols may vary across ethnicity, sex, and disease status. PMID- 17274211 TI - Blood pressure responses of sedentary African American women during cycle and treadmill exercise. AB - OBJECTIVE: To examine blood pressure (BP) in sedentary African American women during two exercise intensities on a cycle and treadmill at fixed heart rate (HR) values. METHODS: Blood pressure (BP) and heart rate (HR) were assessed in 44 women (age 33.1 +/- 8.2 years) during cycling and treadmill walking at 40% and 60% heart rate reserve (HRR). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) reactivity differences were evaluated with separate 2 (mode: cycle, treadmill) x 2 (intensity: 40%, 60% HRR) repeated measures analyses of covariance. Separate multiple regression analyses for the cycle and treadmill were performed to examine potential contributors to higher SBP reactivity at 60% HRR. RESULTS: After adjusting for baseline SBP, body mass index (BMI), and age, mean SBP reactivity was higher during cycling compared to treadmill at both levels of intensity (P < or = .05). The DBP reactivity revealed a main effect for mode (P < or = .05) only with cycle DBP reactivity higher than treadmill for both intensities. Cycling significantly predicted SBP at 60% HRR (P < or = .001), accounting for 66% of the variance in SBP reactivity. However, in both regression models, baseline SBP was inversely related to SBP reactivity (P < or = .01). CONCLUSIONS: At fixed HR values, after adjusting for baseline BP, BMI, and age, BP reactivity is mode dependent and greater for cycling than treadmill exercise at both low and moderate exercise intensity. Baseline SBP is inversely related to the magnitude of SBP reactivity after controlling for the effects of BMI and age. PMID- 17274212 TI - Ethnicity, language, specialty care, and quality of diabetes care. AB - OBJECTIVE: To investigate ethnicity, language, specialty care, and quality of diabetes care in one medical center. METHODS: Retrospective review of computerized records of patients with diabetes age > or = 50 years who were regularly cared for in general medicine, family practice, or diabetes clinics from 1997 to 2000. Measures of processes of care were tests for creatinine, cholesterol, hemoglobin A1C (HbA1C), and microalbumin; ophthalmologic care; and total visits. Intermediate outcomes were average systolic blood pressure (SBP) < 140 mm Hg and HbA1C < 8%. RESULTS: Among 1323 patients, test rates for creatinine, cholesterol, microalbuminuria, and HbA1C were 76.6%, 54.7%, 17.2%, 78.8%, respectively. Only 31.0% had ophthalmology visits, 57.4% had SBP < 140 mm Hg, and 62.0% had HbA1C < 8%. In multivariate analyses, African Americans, Asians, and Latinos received more tests and had more total visits than Whites. Intermediate outcomes were similar except that Asians were more likely (odds ratio [OR] = 1.78, 95% confidence interval [CI] 1.26-2.50) to have SBP < 140 mm Hg. Limited English proficient patients had more total visits (7.0) than English speakers (6.5) (P = .01). Compared to patients with only primary care, patients with a diabetes specialist had more microalbuminuria (OR 3.04, 95% CI 1.87-4.95) and HbA1C (OR 1.91, 1.12-3.26) tests, while those with both types of care were more likely to have each of the five process measures but less likely to have HbA1C < 8%. CONCLUSIONS: Quality of diabetes care was suboptimal for most patients. No ethnic disparity was seen in intermediate outcomes, which may have been achieved through more tests and visits. Combined care by primary and diabetes clinicians may be optimal. PMID- 17274214 TI - Autoimmunity does not contribute to the highly prevalent glucose metabolism disturbances in a Japanese Brazilian population. AB - The Japanese Brazilian population has one of the highest prevalences of diabetes worldwide. Despite being non-obese according to standard definitions, their body fat distribution is typically central. We investigated whether a subset of these subjects had autoantibodies that would suggest a slowly progressive form of type 1 diabetes. A total of 721 Japanese Brazilians (386 men) in the 30- to 60-year age group underwent clinical examination and laboratory procedures, including a 75-g oral glucose tolerance test and determinations of serum autoantibodies. Antibodies to glutamic acid decarboxylase (GADab) were determined by radioimmunoassay and to thyroglobulin (TGab) and thyroperoxidase (TPOab) by flow cytometry assays. Mean body mass index was 25.2 +/- 3.8 kg/m2, but waist circumference was elevated according to the Asian standards. Diabetes, impaired glucose tolerance, and impaired fasting glycemia were found in 31%, 22%, and 22%, respectively, and 53% of the subjects had metabolic syndrome. Glutamic acid decarboxylase (GADab) was positive in 4.72%, TGab in 9.6%, and TPOab in 10% of the whole sample. When participants were stratified according to the presence of thyroid antibodies, similar frequencies of GADab were found in positive and negative groups. The prevalence rates of glucose metabolism disturbances did not differ between GADab positive and negative groups. Our data did not support the view that autoimmune injury could contribute to the high prevalence of diabetes seen in Japanese Brazilians, and the presence of co-morbidities included in the spectrum of metabolic syndrome favors the classification as type 2 diabetes. PMID- 17274215 TI - Associations between ethnicity and child health factors in New Zealand. AB - OBJECTIVES: To identify associations between material and behavioral factors in relation to health among Maori, Pacific, and New Zealand European or other (NZEO) children in New Zealand. DESIGN: Cross-sectional using a two-stage random clustered sampling procedure. PARTICIPANTS: 3,275 children: 37.4% Maori, 32.3% Pacific, and 30.3% NZEO. MAIN OUTCOME MEASURES: Prevalence of demographic, socioeconomic, food security, physical/lifestyle, dietary, and dental factors by ethnic group. RESULTS: Proportionally more Maori and Pacific children, respectively, lived in large households, and approximately one quarter of each group had an annual household income < dollar 20,000. Approximately one fifth of Maori and Pacific households respectively relied on food banks when they did not have enough money for food, and more Pacific household occupants felt stressed when food could not be provided for social occasions. A higher proportion of Pacific children were obese. Approximately 40% of Maori and NZEO children did not play physically active games, and almost four fifths of Maori children had watched television every night the previous week. A higher proportion of Pacific children ate breakfast on the way to school or purchased their school lunch. More than half the Maori and Pacific children had consumed a chocolate bar or soda > or = 4 times the previous month, and a higher proportion of Pacific children added sugar to hot beverages. Proportionally more Maori children had received a restoration or experienced dental pain at night, and a higher proportion of Pacific children had received an extraction due to dental caries. CONCLUSIONS: Marked differences were found in material and behavioral outcomes in relation to child health when ethnicity was considered. PMID- 17274213 TI - Effectiveness of transcendental meditation on functional capacity and quality of life of African Americans with congestive heart failure: a randomized control study. AB - OBJECTIVE: To evaluate the effectiveness of a Transcendental Meditation (TM) stress reduction program for African Americans with congestive heart failure (CHF). DESIGN: Randomized, controlled study PARTICIPANTS AND INTERVENTION: We recruited 23 African American patients > or = 55 years of age who were recently hospitalized with New York Heart Association class II or III CHF and with an ejection fraction of < .40. Participants were randomized to either TM or health education (HE) group. MAIN OUTCOME MEASURES: Primary outcome measure was six minute walk test; secondary outcomes were generic and disease-specific health related quality of life, quality of well being, perceived stress, Center for Epidemiologic Studies Depression Scale (CES-D), rehospitalizations, brain natriuretic peptide, and cortisol. Changes in outcomes from baseline to three and six months after treatment were analyzed by using repeated measures analysis of variance, covarying for baseline score. RESULTS: For the primary outcome of functional capacity, the TM group significantly improved on the six-minute walk test from baseline to six months after treatment compared to the HE group (P = .034). On the secondary outcome measures, the TM group showed improvements in SF 36 subscales and total score on the Minnesota Living with Heart Failure scale. On the CES-D, the TM group showed significant decrease from baseline to six months compared to the HE group (P = .03). Also, the TM group had fewer rehospitalizations during the six months of followup. CONCLUSIONS: Results indicate that TM can be effective in improving the quality of life and functional capacity of African American CHF patients. Further validation of outcomes is planned via a large, multicenter trial with long-term follow-up. PMID- 17274216 TI - Beliefs about tobacco use in African Americans. AB - OBJECTIVES: The purpose of this study was to describe beliefs about the influence of genetic and environmental factors on tobacco use among African Americans and to identify factors that are independently associated with these beliefs. DESIGN AND SETTING: Participants were 94 adult African American men and women who were enrolled in a study on race, genetics, and smoking. MAIN OUTCOME MEASURES: Beliefs about factors involved in smoking initiation and cessation were evaluated by self-report during a structured telephone survey. RESULTS: Smoking status was not associated significantly with beliefs about the influence of genetic or environmental factors; however, gender and education level were associated significantly with beliefs about the influence of environmental factors. Men (beta = -1.71, P = .01) reported significantly greater beliefs about the influence of environmental factors on tobacco use compared to women. Higher education was also associated with greater beliefs about the influence of environmental factors (beta = 1.81, P = .01). Only income level was associated significantly with beliefs about the influence of genetic factors. Respondents with incomes < or = dollar 20,000 reported significantly greater beliefs about the influence of genetic factors compared to those with higher incomes (beta = .92, P = .02). CONCLUSIONS: These results suggest that African Americans believe that biological factors such as genes play a limited role in tobacco use behaviors. Sociodemographic factors, rather than tobacco use, are important to beliefs about tobacco use among African Americans. PMID- 17274217 TI - The New York City Community Outreach Study: biomedical and mental health status among a community sample of urban Hispanics. AB - OBJECTIVE: This report provides a snapshot of health behavior and risk in one low income, urban, Latino community. As part of a community health and education program, 200 adult residents were asked about their health status and behavior and screened for conditions known to constitute significant health risk. DESIGN: A random sample of 10 buildings around a large community-based organization (CBO) service area was selected to receive personal invitation and/or door-to-door flyers announcing several days of free health screening and education at the CBO. All individuals age > or = 18 years were eligible. Those who received screening were mailed lay descriptions of their results along with recommendations and locations for follow-up, if appropriate. SETTING AND PARTICIPANTS: Participants were adult residents of an economically and medically under-served district in New York City, where Latinos make up approximately 75% of the population. Free screening for high blood pressure, diabetes, high cholesterol, obesity, and depression was provided. MAIN OUTCOME MEASURES: The clinical outcomes of the aforementioned tests constitute the main outcomes of this report. RESULTS: Compared to national estimates for Hispanics, health risk was quite high in this sample, particularly with regard to diabetes and cholesterol. Moreover, participants were much less likely to have insurance or to have a regular source of health care than reported in national studies of Hispanics. CONCLUSIONS: Though site specific, these data provide critical information to local CBOs and can be used as a tool for comparison with national data and Healthy People 2010 goals. PMID- 17274218 TI - Correlates of elevated depressive symptoms among rural African American adults with type 2 diabetes. AB - OBJECTIVE: The study objective was to examine the health-related and sociocontextual correlates of elevated depressive symptoms among rural African American adults with type 2 diabetes mellitus. DESIGN: Cross sectional, observational study. SETTING: Rural communities in central Georgia, United States. PARTICIPANTS: African American patients with type 2 diabetes mellitus (N = 200) were recruited from eight rural counties in Georgia by using community based procedures. METHODS: Participants were assessed on demographics (age, sex, and education), diabetes-related characteristics (health status, time since diagnosis, blood glucose control problems, and hemoglobin A1C level), and psychosocial variables (financial stress, community disadvantage, community support, social support, and patient-healthcare provider relationship quality). Elevated depressive symptoms, as assessed via the Center for Epidemiologic Studies-Depression scale, constituted the dependent variable. RESULTS: Elevated depressive symptoms were present in 30% of the sample. Multiple logistic analysis of the contributors to depression predicted 57% of the variability in depression. Sex, neighborhood disadvantage, health status, hyperglycemic symptoms, social support, and patient-healthcare provider relationship quality predicted depression in multivariate analyses. CONCLUSIONS: Both health-related and psychosocial stressors contribute to depressive symptoms among rural African Americans. Problems in patient-healthcare provider relationships may impede identification of depressive symptoms among these patients. Providers require training and support to identify and treat depression among rural African Americans. PMID- 17274219 TI - Preterm birth among African American and white women with a lifelong residence in high-income Chicago neighborhoods: an exploratory study. AB - OBJECTIVE: To explore the association between race and preterm birth among women with a lifelong residence in high-income neighborhoods. METHODS: Stratified and multivariable logistic regression analyses were performed on the Illinois transgenerational birthfile (infants born 1989-1991 and mothers born 1956-1975) with appended US Census income data. African American (n = 777) and non-Hispanic White (n = 2,327) infants born to mothers with a lifelong residence in Chicago census tracts with median family incomes in the top income quartile were studied. RESULTS: African Americans had a twofold greater preterm (< 37 weeks) birth rate than Whites: 11.6% vs 5.2%, relative risk (95% confidence interval) equaled 2.2 (1.7-2.9). The adjusted (controlling for maternal birth weight, age, education, marital status, cigarette smoking, and prenatal care utilization) odds ratio of preterm birth for African Americans (compared to Whites) equaled 1.2 (.4-2.0). African Americans had a sixfold greater very low birth weight rate (< 1500 g) than Whites: 3.3% vs .6%: relative risk (95% confidence interval) equaled 5.9 (3.1-11.2). The adjusted odds ratio of very low birth weight for African Americans (compared to Whites) equaled 2.4 (1.1-3.9). CONCLUSIONS: A stark racial disparity in the unadjusted rates of preterm birth and very low birth weight exists among women with a lifelong residence in high-income urban neighborhoods; however, the disparity narrows when traditional, individual-level risk factors are mathematically controlled. PMID- 17274220 TI - Preeclampsia among Hispanic women in a Detroit health system. AB - OBJECTIVE: We wished to estimate the incidence of preeclampsia among a group of Hispanic women in the greater Detroit metropolitan area. PARTICIPANTS: We reviewed delivery records of 559 Hispanic women from a Detroit hospital and prenatal records of 134 Hispanic women who received care from an affiliated federally qualified health center in southwest Detroit. DESIGN: A retrospective chart review was conducted. The physician's diagnosis was used to study hospital patients. The health center patients were diagnosed on the basis of criteria established in the National High Blood Pressure Education Working Group Report. RESULTS: In 1998, Hispanic women who delivered at the study hospital had an incidence of preeclampsia or pregnancy-induced hypertension (PIH) of 1.3% (7/559), compared to non-Hispanics 5.3% (118/2241) (chi2(1) = 10.35, P < .05). The relative risk was .24. From health center prenatal records, the incidence of preeclampsia/PIH among the 134 patients was 3.7%. The difference in the incidence of preeclampsia/PlH between delivery records at the hospital (1.3%) and health center prenatal records (3.7%) was not statistically significant (chi2(1) = 1.6, P > .10). CONCLUSION: Among women giving birth at a Detroit hospital, Hispanic women had a lower risk of developing preeclampsia or PIH compared to non-Hispanic women. PMID- 17274221 TI - Racial disparities and trends in radiation therapy after breast-conserving surgery for early-stage breast cancer in women, 1992 to 2002. AB - OBJECTIVES: Clinical guidelines recommend that when breast-conserving surgery is provided as primary therapy for early-stage breast cancer, radiation therapy should follow. We do not know whether racial/ethnic disparities in this therapy exist and how disparities may have changed over time. DESIGN AND PATIENTS: We studied 89,110 women who were diagnosed with incident early-stage (American Joint Committee on Cancer stages I-II) breast cancer at > or = 20 years of age from 1992 through 2002 in 12 geographic areas of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor registries. These women had no history of other cancers and received breast-conserving surgery. Of these subjects, 81,577 (91.5%) were Caucasians and 7,533 (8.5%) were African Americans. RESULTS: From 1992 to 2002, the percentage of cases who received breast conserving surgery without radiotherapy increased from 10.8% to 19.8% for Caucasian women and from 13.6% to 27.7% for African Americans. The gap between African American and Caucasian women slightly increased during this period. When data were controlled for patient and tumor characteristics, year of diagnosis, and geographic area, African American women were 24% less likely than Caucasians to receive the recommended therapy (95% confidence interval: 1.18-1.32). CONCLUSIONS: Although current clinical guidelines recommend that women with early stage breast cancer who are treated with breast-conserving surgery should have subsequent radiation therapy, the percentage of women who did not receive this regimen increased from 1992 to 2002. The gap between African American and Caucasian women has continued from 1992 to 2002. PMID- 17274222 TI - Barriers and facilitators of cervical cancer screening among Hispanic women. AB - Hispanic women are less likely than non-Hispanic white women to utilize Pap test screening. Additionally, Hispanic women have higher rates of cervical cancer than non-Hispanic white women. To better understand the barriers and facilitators for Pap test screening, we conducted 13 focus groups with 84 Hispanic women aged 18 61 years. The moderator guide was developed using the Health Belief Model. These focus groups were part of a larger study aimed at developing intervention materials for women on the US-Mexico border. Most of the women knew about cervical cancer and the Pap test. Perceived benefits of screening were finding cancer early, and feeling good about taking care of one's health. Personal barriers to having the test included embarrassment, fear, and pain. System barriers included physician gender and insensitivity to patient needs. Although the male partner was mentioned as a possible barrier in every group, most women expressed that this was not an issue for them personally. Facilitating factors fell into three categories: information/education, low cost or free tests, and supportive physicians and friends. Results of the focus group study were used in the subsequent development of a survey instrument and an intervention in a larger study. PMID- 17274223 TI - Racial and ethnic disparities in self-monitoring of blood glucose among US adults: a qualitative review. AB - OBJECTIVE: To review existing data to determine whether racial/ethnic disparities exist for self-monitoring of blood glucose (SMBG) among adults in the United States. STUDY DESIGN: A literature search of diabetes-related studies published from 1970 through June 2005 was conducted. Our search strategy included SMBG in minority populations with diabetes. METHODS: Studies were selected for review if they reported SMBG rates from a specific racial/ethnic minority group or if there were comparisons of SMBG rates across racial/ethnic groups. RESULTS: Twenty-two studies were reviewed that met the search criteria. Twelve studies included data from a single racial/ethnic minority group, and 10 studies included comparisons between non-Hispanic Whites and at least one racial/ethnic minority group. Data represented studies conducted in a variety of settings, such as healthcare facilities in a state or region of the United States and nationally representative surveys. Most of the data indicate that SMBG rates are generally low, regardless of the population. In comparative studies, some racial/ethnic differences overall were found in SMBG rates among all racial/ethnic minority groups when compared to non-Hispanic Whites. Across studies, patients taking insulin performed SMBG more frequently than did those not taking insulin. CONCLUSIONS: Despite widespread recommendations for self-monitoring of blood glucose, compliance is reported to be low in all groups in the United States, especially among racial/ ethnic minorities. PMID- 17274224 TI - Racial and ethnic differences in cardiovascular disease risk factors: a systematic review. AB - OBJECTIVE: This systematic review was undertaken to expand our understanding of the factors associated with racial/ethnic disparities in cardiovascular disease (CVD) risk factors (hypertension, diabetes, obesity, hypercholesterolemia, no leisure-time physical activity, and smoking), to assess the potential differences in the CVD risk factors by race/ethnicity, and to update and expand on existing reviews. METHODS: English-language, population-based CVD studies published between 1995 to present, which included one or more ethnic comparison in an adult population were reviewed. RESULTS: Sixteen studies were included in this review. Most of the studies found hypertension to be significantly higher in Blacks than Whites. Minority status was also significantly associated with diabetes. No one racial/ethnic minority population was consistently found to have a higher or lower prevalence of obesity or hypercholesterolemia. Mexican Americans had a significantly lower prevalence of smoking than Whites and Blacks; American Indian/Alaskan Natives (AIANs) had significantly higher prevalence of smoking compared to Whites. Mexican Americans had the highest prevalence of no leisure time physical activity, followed by AIANs and Blacks. CONCLUSION: Cardiovascular diseases are the leading cause of death in the United States, and disproportionate rates are seen in racial and ethnic minority populations. Systematically assessing and quantifying modifiable CVD risk factors is therefore crucial in these populations. Better understanding and awareness of the disparities of CVD risk factors by race and ethnicity may help clinicians and public health professionals develop culturally sensitive interventions, prevention programs, and services specifically targeted toward risk burdens in each of these populations. PMID- 17274226 TI - For the patient. Obesity and lung function in Navajo and Hopi children. PMID- 17274225 TI - Commentary: fatalismo reconsidered: a cautionary note for health-related research and practice with Latino populations. AB - Over recent years, interest has grown in studying whether fatalismo (fatalism) deters Latinos from engaging in various health promotion and disease detection behaviors, especially with regard to cancer screening. This commentary presents problematic issues posed by the concept of fatalism, focusing on research on Latinos and cancer screening. We discuss key findings in the literature, analyze methodologic and conceptual problems, and highlight structural contexts and other barriers to health care as critical to the fatalism concept. Although the need to better understand the role of fatalistic beliefs on health is great, we discuss the public health implications of reaching premature conclusions concerning the effect of fatalism on Latinos' cancer screening behaviors. PMID- 17274227 TI - For the patient. Patients with diabetes: using blood glucose self-monitoring may help avoid visits to the hospital. PMID- 17274228 TI - For the patient. Do Black and White women think the same about how race affects their weight? PMID- 17274229 TI - For the patient: Black-white differences in hypertension among adult women and men. PMID- 17274231 TI - For the patient. Metabolic syndrome is not alike across race and ethnicity. PMID- 17274230 TI - For the patient. Health in a Hispanic inner-city community: heart disease risk factors found at high rates. PMID- 17274232 TI - For the patient. Childhood obesity among Head Start children in southeastern Minnesota. PMID- 17274233 TI - For the patient. Understanding how exercise can reduce high blood pressure. PMID- 17274234 TI - Control of HIV/AIDS and AIDS-related conditions in Africa with special reference to periodontal diseases. AB - The HIV/AIDS pandemic, described as one of the worst in human history, is having devastating consequences on the African continent. With 70% of the world's HIV infected population living in sub-Saharan Africa, the economic, social and health care challenges are staggering. While synthesis of effective vaccines is still at an early stage, containment of the pandemic requires a holistic response through an integrated approach of prevention, treatment and improvement in living conditions. Highly active antiretroviral therapy (HAART) has had a major impact on HIV-related deaths and illnesses. The goal of antiretroviral therapy is the maximum suppression of viral load, restoration or preservation of immune function, improvement of quality of life and reduction of HIV-related morbidity and mortality. The spectrum of periodontal diseases in individuals infected with HIV includes unusual forms of gingivitis, necrotising diseases, exaggerated periodontitis and a host of oral mucosal conditions. Treatment includes professional plaque control, debridement to remove necrotic debris, irrigation with antiseptic mouthwashes (chlorhexidine, povidone iodine) and the use of systemic antibiotics in selected cases. It is imperative that research continues in order to better understand the periodontal diseases associated with HIV infected individuals and design evidence-based therapeutic regimens. PMID- 17274235 TI - Frequency of detection of periodontopathic and superinfecting bacteria in HIV positive patients with periodontitis. AB - OBJECTIVE: The aim of this investigation was to establish the frequency of detection of periodontopathic bacteria and Gram-negative enteric rods in HIV positive (HIV+) patients with periodontitis. MATERIALS AND METHODS: Clinical parameters and microbiological samples were obtained from 31 HIV+ periodontitis (H+PG) patients, 32 HIV-negative (HIV-) periodontitis (H-PG) patients and 32 systemically and periodontally healthy (CG) patients. Microbial samples were analyzed using culturing techniques for periodontopathic and superinfecting microorganisms. The ANOVA test was used to assess differences in the clinical parameters, and the Chi square and two-tailed Mann Whitney tests were used to find differences in the composition of the microbiota (p < 0.05). RESULTS: The frequency of detection of periodontopathic bacteria was higher in HIV- periodontitis patients (p < 0.05) compared to HIV+ and healthy subjects. In contrast, HIV+ patients harbor higher levels of superinfecting microorganisms (p < 0.05). Pseudomonas aeruginosa, Enterobacter cloacae and Klebsiella pneumoniae were identified. CONCLUSIONS: The frequency of detection and levels of periodontopathic bacteria were higher in the HIV- periodontitis patients compared to HIV+ patients and healthy subjects. In contrast, levels of superinfecting bacteria were found to be elevated in HIV+ periodontitis patients. Special attention should be paid to the presence of periodontopathic and superinfecting bacteria in these patients in order to avoid further periodontal and systemic complications. PMID- 17274236 TI - Effects of herbal mouthwash containing the pericarp extract of Garcinia mangostana L on halitosis, plaque and papillary bleeding index. AB - OBJECTIVES: To determine the effects of herbal mouthwash containing the pericarp extract of Carcinia mangostana L on volatile sulfur compound (VSC) levels, plaque index (PI) and papillary bleeding index (PBI) in gingivitis subjects and the recurrence of these parameters after periodontal treatment. METHODS: Sixty subjects who were diagnosed as having mild or moderate chronic gingivitis were randomly distributed into herbal or placebo mouthwash groups. On day 1, all parameters were recorded. Subjects rinsed with the assigned mouthwash and VSC was measured at 30 min and 3 h post-rinsing. For the following 2 weeks, subjects practiced their usual oral hygiene and rinsed with the assigned mouthwash twice daily after tooth brushing. On day 15, parameters were recorded. In the 4-week washout period that followed, subjects received scaling and polishing. After another baseline examination, they were re-randomized into the herbal or placebo group and rinsed with mouthwash for 2 weeks. All parameters were re-evaluated on day 15. RESULTS: All parameters were significantly different compared to baseline in both groups at 30 min, 3 h and day 15 (p < 0.05). When compared between groups, VSC was significantly different at day 15 (p < 0.05). After scaling, poloshing and rinsing with mouthwash for 2 weeks, PI and PBI were significantly different compared to baseline (p < 0.05) while VSC was not (p > 0.05). When compared between groups, VSC was significantly different (p < 0.05). CONCLUSION: Herbal mouthwash containing the pericarp extract of G. mangostana may be used as an adjunct in treating oral malodor. PMID- 17274237 TI - The role of psychoneuroimmune interactions in the pathogenesis of ligature induced periodontal disease in Wistar rats. AB - The aim of the present study was to determine the role of chronic stress in the pathogenesis of ligature-induced periodontal disease in rats. Fifty-three Wistar rats were randomly assigned to 4 experimental groups: 1--ligature; 2--ligature + stress; 3--stress only; 4--control. After 30 days the animals were sacrificed, blood samples were collected and histological sections were made for histometric analysis. The stress parameters evaluated were weight of thymus, spleen, adrenal glands and plasma glucocorticoid levels. Analysis of adrenal glands showed statistically significant differences between stressed and non-stressed groups (one-way ANOVA, p < 0.05). Plasma glucocorticoid levels were higher in Group 3 and lower in Group 2 (81.1 nmol/I versus 62.5 nmol/l, p < 0.05). Histometric measurements from the bone crest and from the first attached fiber were taken for all groups and for Groups 1 and 2 for the sites with and without ligatures. The ligature sites always displayed higher mean values than non-ligated sites (paired sample t test, p < 0.05). No statistically significant differences were observed between Groups 1 and 2 with regard to the ligated sites. However, differences were observed between Groups 1 and 2 in histometric bone levels in the non ligated sites (mean values of 0.81 and 0.55 mm, respectively, p < 0.05). It may be concluded that stress can have a possible role in the activation of the hypothalamus-pituitary-adrenal (HPA) axis, with different levels of glucocorticoid release. PMID- 17274238 TI - [Oral and maxillofacial surgery in The Netherlands: from Esser until today]. AB - In 2006, it was 50 years ago that the oral and maxillofacial surgery was officially recognized as a dental speciality in The Netherlands. During those five decades, oral and maxillofacial surgery significantly evolved, which is nicely reflected by the changes in the name of the scientific society supporting the speciality. Originally its name was The Netherlands Society for Oral Surgery and Surgical Prosthodontics, but in 1975 its name was changed into The Netherlands Society for Oral Medicine and Oral Surgery, and in 2006 into The Netherlands Society for Oral Medicine and Oral and Maxillofacial Surgery. Esser is considered to be the first oral and maxillofacial surgeon in The Netherlands. In The Netherlands, 2 schools of oral and maxillofacial surgery are recognized: the Utrecht School with Tjebbes as its founder and the Groningen School with Hut as its founder. Because of the 50th anniversary of the speciality, a thematic issue of the Dutch Journal of Dentistry offers a review of the current status of and expected future developments in oral medicine, head and neck oncology, maxillofacial traumatology, growth and development disorders of the maxillofacial skeleton, temporomandibular joint disorders and reconstructive surgery in The Netherlands. PMID- 17274239 TI - [Mouth diseases and the position of oral medicine]. AB - The field of oral and maxillofacial surgery has greatly evolved during the last five decades. In The Netherlands, oral medicine is covered by the specialist in oral and maxillofacial surgery. Related to the increase in the ageing of the population, it is expected that both the dentist and the family dentist will more and more faced by patients with less usual oral disorders, either as a sign of a local disease or as a sign of a general (systemic) disease. Regarding research, there is a trend of a shift from therapeutic towards innovative research. Therapeutic research is mainly aimed at treating symptoms, whereas innovative research tries to increase insight in development of a disorder or to prevent the development of that disorder or to reduce its progression. PMID- 17274240 TI - [Oral and maxillofacial surgery: mandatory link in the chain of head and neck oncology patient care]. AB - The incidence of head and neck tumors in The Netherlands is rising, mainly due to increasing numbers of oral and pharyngeal carcinomas. Notwithstanding good opportunities for early detection by inspection and palpation, there appears to be a tendency to detect cancer of the head and neck in its later stages. Dentists and physicians, therefore, need to become aware of the early signs of head and neck cancer, and to keep their knowledge up to date. The oral and maxillofacial oncologist operates both as a gatekeeper specialist and as a participant in the multidisciplinary head and neck oncology team, treating patients with referrals from other disciplines. His input in the team is substantial because of his specific knowledge of treatment of tumors, and also on account of his expertise in the possibilities for reconstruction and functional restoration of defects following ablative surgery. PMID- 17274241 TI - [Cranio-maxillofacial traumatology]. AB - During the last 50 years, significant developments have taken place in the treatment of cranio-maxillofacial fractures. The aim of treatment is to achieve the most complete possible restoration of facial functions Epidemiologic figures for these fractures are sparsely available in the literature, but traffic accidents, acts of violence and sports injuries appear to be the main causes. Currently, treatment of facial trauma is aimed at early and (nearly) complete restoration of function. To achieve this goal almost exclusive use is made of stable osteosynthesis methods in The Netherlands. An optimal fixation method exists for nearly every cranio-maxillofacial trauma due to the availability of a large variety of osteosynthesis materials, from micro-plates to reconstruction plates. PMID- 17274242 TI - [Disturbances of growth and development of the maxillofacial skeleton]. AB - Due to many developments in oral and maxillofacial surgery, the contribution of oral and maxillofacial surgeons in the diagnostics and treatment of growth and development disorders of the craniomandibulo-maxillofacial skeleton has become more and more important. Many disorders are treated by multidisciplinary teams including orthodontists and prosthodontists. Arbitrarily, 3 categories of growth and developmental disorders can be distinguished: dento-alveolar, dento maxillofacial, and dento-maxillo-craniofacial disorders. In addition to classic bony reconstruction methods, new methodologies have been developed, such as distraction osteogenesis and simultaneous skin and soft tissue corrections. For many decades, the treatment of growth and development disorders has been a frequent subject of doctoral dissertations in The Netherlands. Attention is currently being paid to developing methods for three-dimensional planning and correction of these disorders, and methods which are minimally invasive. PMID- 17274243 TI - [Mandibular pain and movement disorders, focusing on the temporomandibular joint]. AB - The most important characteristic of temporomandibular disorders is musculoskeletal pain, eminating from the temporomandibular joint and/ or the associated masticatory muscles. The most common temporomandibular disorders involve a balance disturbance of joint loading and the adaptive capacity of joint tissues. Etiological factors leading to such disturbance are largely unknown still. Most cases show an increase in intra-articular friction and associated mechanical joint disturbance. Future research efforts should focus both on factors affecting the adaptive capacity of joint tissue and on reducing their influence. PMID- 17274245 TI - Leading with confidence means you sometimes take chances. PMID- 17274244 TI - [Reconstruction of defects in the oral and maxillofacial region. A review of the various options for treatment]. AB - Reconstructing defects of the oral cavity or face often poses a significant challenge to the surgeon. Defects of the oral and maxillofacial region can be closed with surgical techniques, with prosthetic constructions, or a combination of these techniques. Both defects of bone, soft tissue and teeth can be reconstructed with these techniques. The aim of reconstructing an oral or facial defect is to obtain optimal function and aesthetics which closely approximate the original form and function. Endosseous implants appear to be useful for retaining prosthetic constructions. PMID- 17274246 TI - Medicare cuts, patient safety pose major challenges for medical practices. PMID- 17274248 TI - Promote yourself from manager to leader. PMID- 17274247 TI - Physicians: working harder and enjoying it less. PMID- 17274249 TI - Trials without tribulations. PMID- 17274250 TI - Patient safety: no room for compromise. PMID- 17274251 TI - What is your role in patient safety? AB - As a medical practice executive, you may see patient safety as falling outside the scope of your responsibility. You may look to physicians, nurses and other clinical staff to provide the leadership--and the expertise--to ensure safe care. But a close how and why patient injuries occur in health care organizations makes it clear that executives play a key role in reducing the frequency and severity of those injuries. PMID- 17274252 TI - Gear up for good governance. AB - How administrators help medical practice leaders mak better decisions Although governance challenges can test an administrator's mettle and credibility in many ways, they are no less important to an organization's long-term survival than tending to billing, collection or other key processes. To keep a practice running smoothly and headed in the right direction, an administrator must facilitate decision-making at the board level--and be part of the process. PMID- 17274253 TI - Question authority. AB - Governance means different things to different people, but the fundamentals of good leadership apply regardless of group size, scope or organizational formality. Give your medical group's governance structure and processes the once over to see if they measure up. PMID- 17274255 TI - Colic in combat can cost lives. PMID- 17274254 TI - Santa for a cause. PMID- 17274256 TI - Descriptive summary of patients seen at the surgical companies during Operation Iraqi Freedom-1. AB - The Navy-Marine Corps Combat Trauma Registry is a data repository summarizing information from data sets describing injuries sustained and treatments administered to casualties from the point of injury to rehabilitation. Among the medical facilities contributing data to the Combat Trauma Registry during Operation Iraqi Freedom were the Marine Corps forward surgical companies. The surgical companies offer resuscitative surgery, medical treatment, and temporary holding facilities, in addition to preparing patients for evacuation. This article reviews the types of patients admitted and treatments provided at the surgical companies during the major combat period of Operation Iraqi Freedom. The surgical companies saw an average of 15 to 17 patients per day during this period. Less than 20% of the U.S. casualties seen were wounded in action. In contrast, >75% of the enemy prisoner of war presentations were for battle injuries. Less than 15% of the patients were held at the facilities for >24 hours. PMID- 17274257 TI - Chronic gastrointestinal symptoms of Thomas "Stonewall" Jackson following Mexican American War exposure: a medical hypothesis. AB - In a recent study, a large proportion of veterans seen for chronic heartburn or dyspepsia after the Persian Gulf War had evidence for Helicobacter pylori. Thomas Jackson was born and raised in an area of West Virginia that has a high prevalence of H. pylori. He suffered chronic dyspeptic symptoms following his service in the Mexican-American War. Therapies that he tried included treatment with a variant of the Sippy diet. Following a bullet wound to the left arm at the battle of Chancellorsville on Saturday, May 2, 1863, Thomas Jackson underwent amputation of the left arm below the left shoulder. He died 1 week later with a diagnosis of pleuropneumonia. The records of the postsurgical course are incomplete. The available clinical information raises the hypothesis that his chronic dyspepsia and his cause of death could have been related to chronic peptic ulcer disease due to gastric H. pylori infection. PMID- 17274258 TI - Women in war: operational issues of menstruation and unintended pregnancy. AB - With rapid and frequent deployments around the world, the current high level of military operations demands combat readiness of every military member. In the U.S. Armed Forces, women represent 15% of active duty troops and 17% of reserve and Guard troops and are a critical component for mission accomplishment. The operational issues of menstruation and unintended pregnancy, unique to this population, can decrease a female member's military readiness and affect her ability to deploy. Strategies to mitigate and even eliminate these concerns include the optional use of hormonal medications to induce reversible menstrual cycle suppression. These medications, traditionally indicated for contraception, should be considered essential for female troops during training and deployment. This article, tailored specifically for military women, provides valuable information regarding the risks and benefits, as well as the various options available for menstrual cycle suppression. PMID- 17274259 TI - Efficacy of the blizzard blanket or blizzard blanket plus thermal angel in preventing hypothermia in a hemorrhagic shock victim (Sus scrofa) under operational conditions. AB - The prevention of hypothermia in military casualties under field conditions is challenging. The efficacy of a baffled reflective Blanket (Blizzard Blanket), a portable intravenous fluid warmer (Thermal Angel), and wool Blankets (control) in preventing hypothermia was tested under military field conditions in a swine hemorrhagic shock model. Fifteen pigs were bled at 10 degrees C. After 45 minutes, Hextend was administered (groups 1 and 3, at 10 degrees C; group 2, via Thermal Angel); groups 2 and 3 were encircled with a Blizzard Blanket. After 120 minutes, the pigs were moved to 21 degrees C to simulate a field hospital; group 1 was covered with Blankets. Blood was administered (groups 1 and 3, at 4 degrees C; group 2, via Thermal Angel) with 180 minutes of monitoring. The core temperature was <35 degrees C in five of five control pigs, four of five Blizzard only pigs, and one of five Thermal Angel plus Blizzard Blanket pigs. The Blizzard Blanket limited but did not prevent hypothermia. The Thermal Angel plus Blizzard Blanket combination prevented hypothermia. The Thermal Angel is useful for bolus administration when electricity is limited; its military field use is constrained by battery weight and battery life. PMID- 17274260 TI - Superior mesenteric artery syndrome in a basic military trainee. AB - We present the case of a 19-year-old woman with feeding intolerance, due to superior mesenteric artery (SMA) syndrome, after weight loss experienced during basic military training. She had previous good health and presented with vomiting 8 weeks after starting military training. She had experienced a 16-pound (7 kg) weight loss during the course of training and was increasingly unable to tolerate meals, solids worse than liquids. Computed tomography of the abdomen with oral contrast revealed gastric and duodenal distention, with narrowing of the second portion of the duodenum at the SMA. A nasojejunal feeding tube was placed and she was given tube feedings. Weight increased and she eventually tolerated oral feedings. She completed military training and remains in good health. SMA syndrome is a rare cause of feeding intolerance, but can follow periods of acute weight loss, as is experienced by some basic military trainees. PMID- 17274262 TI - U.S. military enlisted accession mental health screening: history and current practice. AB - Through the stimulus of war and concerns about neuropsychiatric disability, the U.S. military developed methods to rapidly screen the mental health of World War I and II draftees. Intelligence testing and brief psychiatric screening expanded the accession physical examination and underwent revision to identify only gross mental health disability. Supplemental psychiatric evaluations and written psychological screening tools were abandoned after postwar assessments; they demonstrated poor predictive power in evaluating recruit service capacity for combat environments. Currently, only three mental health accession tools are used to screen applicants before their entrance into military service, namely, educational achievement, cognitive testing, and a cursory psychiatric evaluation. The Navy and Air Force use a fourth screening measure during entry-level training. Educational attainment with high school graduation has been the strongest predictor of finishing a service term. The purpose of this article is to provide both a historical review and a review of testing efforts. PMID- 17274261 TI - A comparison of veteran and nonveteran motivations and reasons for participating in clinical trials. AB - OBJECTIVE: Knowledge of distinct motivations and reasons toward or against future trial participation is invaluable to any organization conducting trial research. Study delays often occur due to lack of recruitment. This study's primary objective was to compare veteran and nonveteran motivations and reasons. METHODS: People in two outpatient waiting rooms were approached. The questionnaire assessed motivation toward trial involvement through use of five-point Likert type scales and hypothetical trial scenarios; it also analyzed reasons for participation through subject ranking of reasons. RESULTS: Veterans were more likely to participate in a trial in which all participants received the active treatment (p = 0.025). Veterans had different reasons for participation than nonveterans. Specifically, veterans felt altruism and "paying back" people who treated them were more important (p = 0.024 and p = 0.003) while financial compensation for volunteering was less important (p < 0.001). CONCLUSIONS: Knowledge of the varying reasons for participation could potentially aid recruitment efforts. PMID- 17274263 TI - Readiness estimate and deployability index for Air Force nurse anesthetists. AB - Air Force (AF)-certified registered nurse anesthetists (CRNAs) play an important role in the support of the global war on terror. The purpose of the investigation was to use an AF CRNA-specific modification of the Readiness Estimate and Deployability Index Revised for AF Nurses to assess readiness for deployment. Dimensions included clinical competency, operational competency, soldier/survival skills, personal/psychosocial/physical readiness, leadership and administrative support, and group integration/identification. Readiness skills verification for AF CRNAs was used to develop clinical competency questions. Validity was assessed by two experts, and internal consistency reliability was evaluated by using Cronbach's alpha. Available stateside AF CRNAs (n=105) were surveyed, with a 60% response rate. Descriptive statistics were used to describe the sample, providing a mean score for each variable. Using a 5-point scale, participants rated themselves with an overall readiness score of 4.09, which suggests that AF CRNAs perceive themselves as ready to deploy. PMID- 17274265 TI - Psychophysiological assessment of stress and screening of health risk in peacekeeping operations. AB - Medical surveillance for military personnel participating in peacekeeping missions (PKMs) is required to define the effect of stress on health status. The aim of this study was to determine the effect of stress on the autonomic cardiovascular control and health risk of 72 Bulgarian peacekeepers participating in a PKM in Kosovo. The assessment of psychophysiological stress and determination of stress characteristics were implemented with analysis of heart rate variability and personal interviews. As a response to the cumulative exposure to the effect of stress on cognitive function, we observed reductions in parasympathetic function and baroreceptor modulation of heart rhythm. The alteration in cardiovascular control was registered as decreases in short-term variability and spectral powers of cardiointervals in the respiratory sinus arrhythmia and Traube-Hering-Mayer bands. The advantage of psychophysiological stress assessment and screening of health risk in PKMs is that results indicate the mechanisms of the effects of stress on cognitive function and health status. PMID- 17274266 TI - The Joint Military Medical Executive Skills initiative: an impressive response to changing human resource management rules of engagement. AB - Confronted with a sudden and substantial change in the rules regarding who could command a military medical treatment facility (MTF), the Military Health System (MHS) responded to the challenge with an impressive human resource management solution-the Joint Medical Executive Skills Program. The history, emergence, and continuing role of this initiative exemplifies the MHS's capacity to fulfill the spirit and intent of an arduous Congressional mandate while enhancing professional development and sustaining the career opportunities of medical officers. The MHS response to the Congressional requirement that candidates for MTF command demonstrate professional administrative skills was decisive, creative, and consistent with the basic principles of human resource management. The Joint Medical Executive Skills Program is a management success story that demonstrates how strategic planning, well-defined skills requirements, and structured training can assure a ready supply of qualified commanders for the military's MTFs. PMID- 17274264 TI - Perceived stress, heart rate, and blood pressure among adolescents with family members deployed in Operation Iraqi Freedom. AB - This study compared the impact of the 2003 Operation Iraqi Freedom on heart rate (HR) and blood pressure (BP) and self-reported stress levels among three groups of self-categorized adolescents: (1) military dependents with family members deployed; (2) military dependents with no family members deployed; (3) civilian dependents. At the onset and end of the "major hostilities" of Operation Iraqi Freedom, 121 adolescents (mean age = 15.8 +/- 1.1 years) completed questionnaires evaluating the psychological impact of the war and were evaluated for HR and BP. The military deployed dependents exhibited significantly higher HR than other groups at both evaluations (both p < 0.04). Ethnicity by group interactions indicated that European American-deployed dependents had higher stress scores at both time points (p < 0.02). Military dependent European Americans exhibited higher systolic BP compared to the other groups on the second evaluation (p < 0.03). PMID- 17274267 TI - Mortality, length of life, and physical examination attendance in participants of the Air Force Health Study. AB - Begun in 1982, the Air Force Health Study (AFHS) has assessed the mortality of veterans of Operation Ranch Hand, the unit responsible for aerially spraying herbicides in Vietnam. A comparison group of other Air Force veterans involved with aircraft missions in Southeast Asia during the same period, but not involved with spraying herbicides, was included in the study. Among 18,082 veterans, this report examined whether attendance at AFHS physical examinations from 1982 to 1999 played a role in mortality experience and potential lengthening of life relative to veterans who did not attend. The years of potential life lost for 1173 veterans who died before age 65 was calculated. No statistically significant difference in risk of death was found from all causes, cancer, or circulatory disease between attendees and nonattendees. No evidence was found to suggest that attending physical examinations decreased mortality or substantially lengthened life in AFHS participants. PMID- 17274268 TI - Civilian medical qualification determinations. AB - Much like their counterparts in private industry, federal medical officers, particularly preventive and occupational medicine physicians, must ensure a workforce fit to perform their duties. Meeting this objective often requires balancing competing interests between employers and employees. The medical examination is the method for protecting the government's interests in identifying federal civilian applicants and workers who are medically unqualified to perform their duties while also preventing discrimination against qualified individuals with disabilities. Scant published guidance on performing authorized medical examinations and analyzing the resultant information is available for federal medical officers. This is needed to foster an equitable, compliant decision for both federal employers and employees. Using the Department of Defense as an example, this article provides a legal road map for the practitioner by defining medical standards and physical requirements, discussing medical examinations, and examining disability determinations. PMID- 17274270 TI - Correlation of sulfur mustard exposure and tobacco use with expression (immunoreactivity) of p53 protein in bronchial epithelium of Iranian "mustard lung" patients. AB - A unique chronic obstructive pulmonary disease (COPD), provisionally called "mustard lung", which occurs as a late complication of sulfur mustard (SM) exposure among SM-exposed Iranians, is presently poorly characterized. This investigation evaluates p53 immunoreactivity in bronchial epithelium of individuals with histories of tobacco use and/or SM exposure, as a tool to help define mustard lung. In this study, 68 COPD patients were segregated into two groups, 35 mustard-exposed patients (including 8 smokers) and 33 unexposed patients (including 16 smokers). Disease severity was assessed with pulmonary function tests. p53 protein in bronchial tissue obtained as biopsies was quantitated by immunostaining. Among nonsmokers, 41.2% of unexposed subjects and 14.8% of exposed subjects expressed p53. Among smokers, 25% of the unexposed group and 50% of the exposed group expressed the protein. Initial data trends suggest an additive contribution of SM exposure and smoking to p53 immunoreactivity. These results illustrate the use of p53 immunoreactivity in the characterization of COPD, including mustard lung. PMID- 17274269 TI - Attrition of U.S. military enlistees with waivers for hearing deficiency, 1995 2004. AB - BACKGROUND: Hearing deficiency is the condition for which accession medical waivers are most commonly granted. The retention of individuals entering service with a waiver for hearing deficiency has not been previously studied. METHODS: Military retention among new enlistees with a medical waiver for hearing deficiency was compared with that among a matched comparison group of fully qualified enlistees. Comparisons according to branch of service over the first 3 years of service were performed with the Kaplan-Meier product-limit method and proportional-hazards model. RESULTS: Army subjects had significantly lower retention rates than did their fully qualified counterparts. In the adjusted model, Army and Navy enlistees with a waiver for hearing deficiency had a significantly lower likelihood of retention than did their matched counterparts. DISCUSSION: The increased likelihood of medical attrition in enlistees with a waiver for hearing loss provides no evidence to make the hearing accession standard more lenient and validates a selective hearing loss waiver policy. PMID- 17274271 TI - Civilian doctors in military clinics--outsourcing for better medicine. AB - OBJECTIVES: To determine whether outsourcing of medical consulting services could improve the quality of medical treatment in military primary care clinics. METHODS: Data were collected prospectively over 2 months in two regular army clinics manned by ordinary army doctors and in two intervention clinics also staffed with senior civilian doctors. The causes for doctor visits, diagnoses, and other patient data were collected. RESULTS: Information was recorded from 4970 soldier visits in the four clinics. Although a prescription of rest days was similar in both types of clinics, the level of tertiary referrals was lower by one-third in the intervention clinics compared to the regular clinics. Surrogate markers for quality of care, such as increased use of planned follow-up and reduced antibiotic use, were significantly better in the intervention clinics, and so was overall patient satisfaction. CONCLUSIONS: Integration of specialist civilian physicians in the military primary care system is highly beneficial and provides better care and saves costs. PMID- 17274272 TI - The influence of water versus carbohydrate-electrolyte hydration on blood components during a 16-km military march. AB - The purpose of this study was to identify and to compare the effects of ingesting liquids during a 16-km military march under moderate environmental conditions. Twenty-six volunteer male subjects were randomly divided into two groups. Group GW received water (n=12), and group GP received an electrolytic carbohydrate solution (n=14). Blood and urine samples were obtained immediately before and after the march. No significant differences between the drinks were found for any of the measured variables. However, important results (p < 0.05) were observed by comparing variables before and after exercise. The variables included sodium, hematocrit, red blood cell, hemoglobin, and lactic acid levels and body weight (group GW) and sodium, potassium, hematocrit, red blood cell, hemoglobin, and lactic acid levels (group GP). Under the environmental conditions and hydration procedures applied, the results of this study showed similarities in the behavior of the variables, regardless of the kind of beverage consumed. PMID- 17274273 TI - Negative first-term outcomes associated with lower extremity injury during recruit training among female Marine Corps graduates. AB - This study assessed the impact of lower extremity injuries and stress fractures during recruit training on first-term outcomes among female Marine Corps graduates. Injury data were collected from women recruits at Parris Island, South Carolina (1995-1999) and negative first-term outcomes were obtained from the Career History Archival Medical and Personnel System. The three negative outcomes included (1) failure to complete first-term of service, (2) failure to achieve rank of corporal, and (3) failure to reenlist. Overall, 22% did not complete their first-term enlistment and 12% of those who did were not promoted to corporal. After adjustment for demographic characteristics, not completing first term and not being promoted to corporal were both associated with injuries or stress fracture during training. Reenlistment was not associated with training injuries. Our findings indicate lower extremity injuries among women undergoing Marine Corps recruit training are associated with poor first-term outcomes even among those who graduate. PMID- 17274274 TI - Incidence of anterior cruciate ligament injury among active duty U.S. military servicemen and servicewomen. AB - Although some studies have reported an increased incidence of anterior cruciate ligament (ACL) injuries in women athletes, little is known about the gender differences in injury patterns in the U.S. military. Using the Defense Medical Epidemiology Database, a search was performed for International Classification of Diseases, 9th Revision (ICD-9) codes 717.83 (old disruption of ACL) and 844.2 (sprain, strain cruciate ligament of the knee) among all servicemen and servicewomen between 1997 and 2003. Multivariate Poisson regression analysis was used to estimate the rate of ACL injuries per 1000 person-years, controlling for age and race, for each ICD-9 code. We computed rate ratios and 95% confidence intervals (CIs) by using male as the reference category. The injury rates for code 717.83 were 3.09 cases per 1,000 person-years for men and 2.29 cases per 1000 person-years for women, controlling for age and race (relative risk, 0.74; 95% CI, 0.71-0.76). The injury rates for ICD-9 code 844.2 were 3.79 cases per 1000 person-years for men and 2.95 cases per 1,000 person-years for women, controlling for age and race (relative risk, 0.78; 95% CI, 0.76-0.80). There was not an observed increase in the incidence of ACL injuries among female soldiers in the U.S. military between 1997 and 2003. PMID- 17274275 TI - Benefits of a musculoskeletal screening examination for initial entry training soldiers. AB - Soldiers reporting for Individual Entry Training from basic training posts frequently arrive unable to initiate or complete training due to musculoskeletal injuries. Therefore, a screening examination was developed to identify musculoskeletal injuries and provide appropriate medical intervention as needed. During a consecutive 5-week period, 1013 soldiers reported for training to Fort Lee, Virginia. Of these, 105 (10.4%) reported for medical screening because they stated that they had an injury or could not pass a physical fitness test. After screening, 76 (72%) were found to have physical restrictions that would limit their ability to fully participate in training. The injured soldiers were referred for and received medical intervention. Of the total number of soldiers screened, 97 (92%) were able to complete their training, pass a physical fitness test, and graduate on time. This study documents the use and benefits of a brief musculoskeletal screening examination for individual entry training soldiers. PMID- 17274276 TI - Heart rate variability in patients with allergic rhinitis. AB - Considering the role of autonomic imbalance in the pathogenesis of hypersensitivity reactions, we evaluated the autonomic system through time-domain analysis of heart rate variability (HRV) in patients with allergic rhinitis. Twenty-four patients with allergic rhinitis and 22 healthy subjects (mean age, 41 +/- 8 years and 37 +/- 9 years, respectively) were enrolled in the study. The diagnosis of allergic rhinitis was based on the history, symptoms, and skin prick tests results. Twenty-four-hour ambulatory electrocardiographic recordings were obtained, and the time-domain indices were analyzed. Analysis of HRV revealed that the SD of normal RR intervals, SD of successive differences in normal cycles, and HRV triangular index were not significantly different between the groups, but the root mean square successive difference, number of RR intervals exceeding 50 milliseconds, and percentage difference between adjacent normal RR intervals exceeding >50 milliseconds were significantly greater in the study group, compared with the control group. Our findings showed that HRV indices, which predict parasympathetic predominance, were increased in patients with allergic rhinitis. This finding shows that vagal activation is present not only in the nose but also in other systems, including the cardiovascular system. PMID- 17274277 TI - Turkish military personnel's expectations for health care services provided to them. AB - OBJECTIVE: The goal was to determine the expectations of patients using the health care services provided in the health care institutions of Turkish Armed Forces (TAF). METHODS: This study was performed between August 2002 and March 2003, with an open-ended question placed on the World Wide Web site of TAF Health Command. The framework was an intranet, which is a special Internet structure across the TAF institutions. Eight hundred four TAF personnel answered by typing their own words in response to the open-ended question. RESULTS: In the data obtained from this study, the participants' expectations focused more on the behaviors they encountered during utilization of the services, the health care personnel-patient relationship, and the services provided by the personnel, rather than the technical options and opportunities presented by the hospitals. CONCLUSIONS: In addition to the efforts and financial resources dedicated to improving the medical technology used in the health care institutions, providing information to the health care personnel about ethically appropriate behavior and patient-health care professional communication and designing new regulations concerning these issues should contribute greatly to the satisfaction of the people receiving health care services and their relatives. PMID- 17274278 TI - Comparison of clinical pathology examination scores and grade point averages of Royal Thai Army medical cadets. AB - This retrospective study assesses the relationship between clinical pathology (CP) examination scores and grade point averages (GPAs) of Royal Thai Army (RTA) medical cadets. Altogether, 411 of the third-year RTA medical cadets studying CP at Phramongkutklao College of Medicine in 1995-2001 were included in this study. Correlations between CP examination scores, clinical year GPAs, and cumulative GPAs were analyzed by using Pearson's product-moment correlation coefficient. The CP scores showed positive correlations (p < 0.01) with GPAs in the clinical years (4th to 6th) of study (r = 0.616, r = 0.602, and r = 0.540) and cumulative GPAs (r = 0.698). These significant findings may be attributable to the integration of small group teaching and case study discussions, together with traditional lectures and laboratory practice, in the CP course. Our results indicate that CP examination scores can be used as a reliable predictor of success in the 6-year course of study for RTA medical cadets. PMID- 17274279 TI - Smoking status and smoke-related gingival melanin pigmentation in army recruitments. AB - This study aimed to define the smoking status and smoke-related gingival melanin pigmentation in army recruitments and was conducted with army recruitments in Sivas. Nine hundred eight subjects were examined. The oral and dental health of those subjects was checked and recorded. The smoking status of the subjects was self-reported and recorded on questionnaires by researchers. The chi2 test and Kruskal-Wallis test were used for statistical analysis. More than one-half of the subjects (54.3%) were primary school graduates and the mean age was 20.2 +/- 0.95 years. The response rate regarding smoking was 100%. Of the respondents, 596 (65.7%) were current smokers, 12 (1.3%) were former smokers, and 300 (33.0%) were never smokers. The gingival melanin pigmentation rate was 27.5% in current smokers and 8.6% in those who never smoked (p = 0.000). Smoking five to nine cigarettes a day appeared to be sufficient to cause gingival melanin pigmentation. The proportion of smokers who had melanin pigmentation did not change after 10 cigarettes a day. A rehabilitation project on smoking prevention and smoking cessation for army recruitments is urgently needed. PMID- 17274280 TI - Case #8: Intralobar bronchopulmonary sequestration. PMID- 17274281 TI - Identification of infectious bursal disease viruses from RNA extracted from paraffin-embedded tissue. AB - After histopathologic screening of bursas of Fabricius for the presence of infectious bursal disease virus (IBDV) lesions, the hypervariable region of the VP2 gene for IBDV was extracted from formalin-fixed paraffin-embedded tissue blocks. With real-time reverse transcription-polymerase chain reaction (RT-PCR) and sequencing, IBDV was identified in 227 different blocks. The ability to identify the actual virus strain associated with the lesions observed microscopically in the bursa of Fabricius allowed for direct correlation between viral identity and lesions, which may help in designing vaccination strategies. Several new emerging viruses that do not group with other known IBDVs in phylogenetic tree analysis were identified, as well as a unique variant virus that had 63 nucleotides missing from its hypervariable region. PMID- 17274282 TI - The effect on pathogenesis of Newcastle disease virus LaSota strain from a mutation of the fusion cleavage site to a virulent sequence. AB - The principal molecular determinant of virulence of Newcastle disease virus (NDV) is the amino acid sequence at the fusion cleavage activation site. To extend the understanding of the role of the fusion cleavage activation site in NDV virulence, the pathogenesis in chickens of a lentogenic LaSota isolate and two infectious clones, NDFL and NDFLtag, were compared. NDFL is an infectious clone of a lentogenic NDV strain (LaSota E13-1), and NDFLtag is the infectious clone with the fusion cleavage site sequence mutated to the virulent motif. NDFL and NDFLtag were described by Peeters et al. The viruses were inoculated intraconjunctivally into groups of 4-wk-old white leghorn chickens and compared in a pathogenesis study for determination of disease causation (clinical signs of disease, gross lesions, histology, virus isolation, and serology) and viral distribution (presence of viral nucleoprotein and mRNA was detected by immunohistochemistry and in situ hybridization, respectively). The modification of the fusion cleavage activation site to the virulent motif in the infectious clone only slightly increased disease severity and viral distribution in the pathogenesis assessment, even though dramatically increased pathogenicity of NDFLtag was confirmed by standard pathogenicity index tests. The result, that the mutated fusion cleavage site of NDV-NDFLtag had only a small influence on pathogenesis in chickens compared to either E13-1 or NDFL, suggests that the pathogenic effects of NDV are not dependent on the fusion cleavage site alone. PMID- 17274283 TI - A comparative study of detecting Chlamydophila psittaci in pet birds using isolation in embryonated egg and polymerase chain reaction. AB - This study, for the first time in Turkey, investigated the existence of Chlamydophila psittaci and determined the prevalence of its disease, chlamydiosis, in pet birds. Polymerase chain reaction (PCR) was compared with other testing methods that have been typically used in the diagnosis of C. psittaci. Fecal specimens (n =96) of avian origin were tested by PCR and two identification methods, modified Gimenez staining (mGS) and direct fluorescein conjugated monoclonal antibody staining (FA). The identification methods were implemented by staining the yolk sacs of embryonated chicken eggs inoculated at 6 days of age and harvested between 3 and 10 days after inoculation. Fecal specimens from pet birds were randomly collected from pet shops and homes. These specimens were then used to isolate C. psittaci and to detect its specific DNA. The inocula that were prepared from fecal specimens were then inoculated into yolks of 6-day-old embryonated chicken eggs. The preparations from egg yolk sacs were examined with mGS and direct FA after three blind passages. The PCR method was used to detect specific DNA in feces. In 96 fecal specimens, 33 (34.4%) were positive with PCR, 21 (21.9%) were positive with mGS, and 29 (30.2%) were positive with FA. Among 33 positive specimens with PCR, 28 specimens were positive with FA, and 20 specimens were positive with mGS. The sensitivity and specificity were 59% and 94% between FA and mGS, and 97% and 93% between FA and PCR, respectively. PMID- 17274284 TI - Molecular analysis of Brazilian infectious bronchitis field isolates by reverse transcription-polymerase chain reaction, restriction fragment length polymorphism, and partial sequencing of the N gene. AB - Molecular analysis of 15 Brazilian infectious bronchitis virus (IBV) isolates, obtained from clinical outbreaks of the disease in chickens (broilers or layers) in the state of Minas Gerais (Brazil) between 1972 and 1989, is reported. Using the N protein gene as target, IBVs were analyzed by reverse transcription polymerase chain reaction/restriction fragment length polymorphism (RT-PCR/RFLP) with the restriction enzymes AvaII, HphI, Sau96I, and Tsp509I and cDNA sequencing. Results obtained from those isolates were compared to 19 sequences available in GenBank. N gene RFLP profiles, cDNA sequences, and predicted amino acid composition were used for the construction of dendrograms. Brazilian isolates were grouped into one distinct group. Identity of predicted N protein amino acid composition varied from 45% (between isolates G and 208) up to 99% (PM 1 and PM2), and, when compared to the other IBVs, the amino acid identity was from 42% (Q3/88 and G) up to 97% (D41 and PM1). The great genetic diversity was shown to occur before the official use of vaccination in Brazil and has remained thereafter. PMID- 17274285 TI - Phenotypic and molecular characterization of isolates of Ornithobacterium rhinotracheale from chickens and pigeons in Taiwan. AB - Forty Ornithobacterium rhinotracheale (ORT) strains were isolated from 28 chickens and 12 pigeons for the first time in Taiwan. All isolates reacted positively in the p-nitrophenyl-beta-D-galactopyranoside (PNPG) and oxidase tests, showing an API 20NE identification system biocode 0-0-2-0-0-0-4. All the pigeon isolates and 85.7% (24 of 28) of the chicken isolates belonged to serotype A. Compared to the ORT ATCC 51464 strain, 14.3% (4 of 28) of chicken isolates and 58.3% (7 of 12) of pigeon isolates showed smaller colonies after 72 hr incubation. Most of the chicken isolates (22 of 28), but none of the pigeon isolates, could agglutinate chicken and pigeon red blood cells. There appears to be a correlation that ORT isolates with a larger colony size tend to be more able to agglutinate red blood cells than the ORT isolates with a smaller colony size. A majority of isolates was sensitive to amoxicillin, ampicillin, ceftiofur, penicillin, and oxytetracycline. The 16S ribosomal RNA (rRNA) sequences of 23 Taiwanese ORT isolates showed high identity (98%-100%) to sequences in GenBank. Phylogenetic analysis of these sequences showed that pigeon isolates formed a distinctive cluster, while chicken isolates and all other 16S rRNA sequences obtained from GenBank belonged to another two clusters. The results indicate that pigeon ORT isolates are different from most chicken isolates in regard to a number of phenotypic and molecular traits. PMID- 17274286 TI - Spatiotemporal distributions of reported cases of the avian influenza H5N1 (bird flu) in Southern China in early 2004. AB - This study investigates spatiotemporal distributions of reported cases of the avian influenza H5N1 (bird flu) in Southern China in early 2004. Forty-nine cases of the avian influenza H5N1 covering a 6-week period (January 19, 2004, through March 9, 2004) were compiled from the Chinese Ministry of Agriculture and the World Health Organization. Geographic information systems (GIS) techniques combined with statistical techniques were used to analyze the spatiotemporal variation of reported cases of avian influenza. Using Oden's direction method, we also explored the spatiotemporal interaction of individual-level avian influenza cases during the study duration. The peak period (temporal clustering) for the epidemiological avian influenza outbreak occurred between the third and fourth weeks. Although we observed a major northeast-southwest distribution of the avian influenza H5N1 cases, there was no significant spatiotemporal association in average "direction of advance" of these cases. The directional finding is very consistent with the major migratory bird routes in East Asia, but owing to weak surveillance and reporting systems in the region, the study findings warrant further evaluation. PMID- 17274287 TI - The development of an exposure risk index as a rational guide for biosecurity programs. AB - Population disease risk can be ranked using an exposure risk index that uses quantitative data on exposure risk factors and the proximity of susceptible animals to disease reservoirs. The reservoir represents the available microbial load (a quantity), derived from the mass of the contaminant, the percentage available for dissemination, the initial microbial content of the contaminant, and its age and half-life. The proximity measurement uses distance from the reservoir to calculate an area over which the microbial exposure might be spread. Dividing the reservoir by the proximity measurement, one obtains an exposure risk measurement that is significantly correlated with veterinarians' perceptions of risk. This exposure risk ranking can be used to rank population disease transmission risks associated with events and practices in animal production. The advantages of the exposure risk index are that it derives an exposure risk measurement from available objective information, it provides a way to compare disparate sources of disease exposure risk, it can be modified for specific diseases, and it provides a foundation for developing and evaluating mitigation strategies. From the exposure risk measurement, mitigation strategies and available resources can be focused appropriately to prevent or control disease. Biosecurity programs and disease control measures can be directed at those areas of greatest risk for spreading disease. PMID- 17274288 TI - Enzootic reticuloendotheliosis in the endangered Attwater's and greater prairie chickens. AB - Reticuloendotheliosis (RE) in captive greater prairie chickens (GPC, Tympanuchus cupido pinnatus) and Attwater's prairie chickens (APC, Tympanuchus cupido attwateri) was first reported in 1998. RE is caused by avian reticuloendotheliosis virus (REV), an oncogenic and immunosuppressive retrovirus infecting multiple species of wild and domestic birds. During August 2004 through May 2006 a captive population of prairie chickens was affected simultaneously with a neoplastic condition and also avian pox, the latter being detected in 7.4% (2 of 27) of all birds submitted for histopathology. A survey for REV was conducted in order to examine its possible role in mortality observed primarily in juvenile and adult specimens of prairie chickens. The investigative procedures included postmortem examinations, histopathology, molecular detection, and virus isolation. In total, 57 Attwater's prairie chickens and two greater prairie chickens were included in the study. REV infection was diagnosed using virus isolation or polymerase chain reaction (PCR) or both in 59.5% (28 of 47) of blood samples and/or tumors from suspect birds. Lymphosarcomas were detected in the tissues of 37% (10 of 27) of the birds submitted for histopathology. Such lymphosarcomas suggestive of RE represented the most frequent morphologic diagnosis on histopathology among 27 separate submissions of naturally dead prairie chickens. Overall, REV was detected or RE diagnosed in 34 of 59 prairie chickens (57.62%). The average death age of all birds diagnosed with lymphosarcomas on histopathology was 2.2 yr, ranging from <1 to 4 yr. Although deaths associated with neoplasia occurred in males and females in equal proportions based on submissions, overall more males were diagnosed as REV infected or RE affected (16 males vs. 7 females, and 11 birds of undetermined gender). Reticuloendotheliosis virus was confirmed as a significant cause of mortality in captive prairie chickens. PMID- 17274289 TI - Pathogenicity of turkey astroviruses in turkey embryos and poults. AB - The pathogenicity of turkey astrovirus 2001 (TAstV2001) and turkey astrovirus 1987 (TAstV1987) in specific-pathogen-free (SPF) turkey embryos and commercial poults was investigated. The virus shedding in poults was monitored using electron microscopy (EM) and reverse transcription-polymerase chain reaction (RT PCR) during the 14-day experimental period. Both viruses caused enteritis and growth depression in SPF turkey embryos and poults. The TAstV2001 did not induce macroscopic or microscopic lesions in thymuses and bursas of embryos or poults. No macroscopic changes were observed in thymuses and bursas of embryos and poults inoculated with TAstV1987, and no statistically significant differences in bursa weight/ body weight ratios (P > 0.05) were detected. However, TAstV1987 infection resulted in microscopic lesions in bursas but not in thymuses of infected embryos and poults. Both TAstV2001 and TAstV1987 were shed during the whole 14-day experimental period as detected by EM and RT-PCR. These findings indicated that both TAstV1987 and TAstV2001 are etiologic agents of turkey enteritis. In addition, TAstV1987 might cause impairment of the immune system of infected poults. The pathogenicity of TAstV1987 is somewhat different from TAstV2001. PMID- 17274290 TI - Molecular characteristics of infectious bursal disease viruses from asymptomatic broiler flocks in Europe. AB - Infectious bursal disease virus (IBDV) exists in several different antigenic and pathogenic forms. The immune suppression caused by this virus in young chickens is not always associated with clinical signs of disease. The antigenic variant viruses originally described in the United States typically do not cause clinical signs of disease but can cause a marked immune suppression via the destruction of B lymphocytes. Using a reverse transcription-polymerase chain reaction (RT-PCR) assay we conducted a survey of asymptomatic broiler chicken flocks in Europe for IBDV. Restriction fragment length polymorphisms in the viral protein 2 (VP2) gene of four isolates from Spain and four isolates from France indicated they may be different from the classic and very virulent (vv) IBDV strains found throughout Europe. Nucleotide sequence and phylogenetic analysis of the hypervariable region of the VP2 gene indicated that all eight viruses were more similar to U.S. variant viruses than classic viruses. In two viruses, one from France and one from Spain, threonine was observed at amino acid position 222 and serine was found at position 254. These two substitution mutations are characteristic of Delaware variant viruses. In addition, all eight viruses had mutated amino acid position 318 from glycine to aspartic acid, another substitution mutation commonly found in U.S. variant viruses. Although importation restrictions prevented us from directly testing the antigenicity of these viruses, their nucleotide and predicted amino acid sequences suggest they could be antigenically distinctive compared to classic and vvIBDV commonly found in Europe. Confirmation of the presence of antigenic variant IBDV strains in Europe requires additional immunologic studies to elucidate the exact nature of the viral epitopes. Our data support the need for these immunologic studies. PMID- 17274291 TI - Development and validation of a real-time Taqman polymerase chain reaction assay for the detection of Mycoplasma gallisepticum in naturally infected birds. AB - In this study, we report the development and validation of a real-time polymerase chain reaction (PCR) assay using a Taqman-labeled probe for the detection of Mycoplasma gallisepticum (MGLP assay). The MGLP assay was highly specific with a detection limit of 25 template copies per reaction and a quantification limit of 100 template copies per reaction. Validation of the assay was completed with 1247 samples (palatine cleft and tracheal swabs) from M. gallisepticum-positive and negative chicken flocks. The MGLP assay was compared to an enzyme-linked immunosorbent assay (ELISA), a conventional polymerase chain reaction assay (mgc2 PCR), and isolation of M. gallisepticum from naturally infected flocks. A total of 805 samples collected from negative flocks, as verified by ELISA and/or mgc2 PCR, were negative by the MGLP assay. A total of 442 samples were collected from positive flocks, of which a total of 228 samples were positive by the MGLP assay. These results agreed for 98.87% of the samples when tested by mgc2 PCR. When comparing the MGLP assay with M gallisepticum isolation, the MGLP assay was more sensitive than isolation for detecting positive birds from a positive flock, 172/265 and 50/265, respectively. Overall, the MGLP assay and M. gallisepticum isolation agreed for 52.8% of the samples tested. In conclusion, the MGLP assay was highly specific, sensitive, and reproducible, and allowed the quantification of template copies directly from clinical samples. PMID- 17274292 TI - Restriction fragment length polymorphism typing of infectious bursal disease virus field strains in Turkey. AB - Infectious bursal disease (IBD), also known as Gumboro disease, is a highly contagious, immunosuppressive disease of immature chickens. It is caused by IBD virus (IBDV) and is responsible for major economic losses in the poultry industry worldwide. In this study, 280 bursa samples from 56 commercially reared chicken flocks in Turkey with clinical symptoms of IBD were examined for IBDVs using the reverse transcription (RT)-polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) assay. The assay was conducted on a 743-bp fragment of the VP2 gene with the restriction enzymes BstNI, MboI, and SspI. The results indicate the existence of field isolates with new molecular patterns different from those previously published that may well be unique and specific to geographical regions. PMID- 17274293 TI - Inclusion body hepatitis as a primary disease in broilers in Saskatchewan, Canada. AB - In recent years inclusion body hepatitis (IBH) has emerged as an economically important disease in Western Canada. Historically, infections with infectious bursal disease virus (IBDV) and chicken anemia virus (CAV) have been known to suppress the immune system of broilers and make them more susceptible to a secondary disease such as IBH. Recently it has been reported that virulent adenoviruses are able to cause IBH as a primary disease in broilers without apparent involvement of IBDV and CAV. The objectives of this study were to examine the possible association of IBH with IBDV and CAV infections in Western Canada and to identify adenoviruses involved in outbreaks. Serum samples from 17 broiler-breeder flocks and their progeny were collected when broilers were hatched and then again from broilers at the time of slaughter, and these samples were tested for IBDV and CAV antibodies by enzyme-linked immunosorbent assay (ELISA). Based on the ELISA titers the antibody response to vaccination against IBDV and CAV was at an expected level in all broiler flocks. Therefore, IBH outbreaks in these flocks were not due to inadequate levels of antibodies against IBDV and CAV. Moreover, there was no correlation found between occurrences of IBH outbreaks in broilers and their IBDV or CAV titers at the time of processing. Viruses that were isolated from livers of birds suffering from IBH could be classified into four different genotypes. Their hexon gene loop 1 sequences showed high percentages of identity to FAdV-7, FAdV-8a, FAdV-8b, and FAdV-11. The results of this study could not demonstrate an association of IBH with IBDV and CAV infections, but they supported the hypothesis that IBH in broilers in Western Canada is a primary disease with no apparent immunosuppressive involvement. PMID- 17274294 TI - A practical tissue sampling method using ordinary paper for molecular detection of infectious bursal disease virus RNA by RT-PCR. AB - A practical sampling method for bursal tissue using ordinary paper for molecular diagnosis of infectious bursal disease (IBD) was established. IBD virus-infected bursa was directly smeared on chromatography paper, filter paper, or stationery copy paper and was then fixed with absolute ethanol, Tris-HCl-saturated phenol, or phenol:chloroform:isoamyl alcohol (25:24:1). Flinders Technology Associates (FTA) card, which is designed for the collection of biological samples for molecular detection, was also used. After storage at 37 C for up to 30 days, total RNA directly extracted from the tissue fixed on the papers and FTA card were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of IBD virus (IBDV) RNA. In addition, the ability of each chemical used in the fixation and the FTA card to inactivate IBDV was evaluated. Regardless of the paper quality, storage period, and fixation method, IBDV RNA was consistently detected in all of the samples. IBDV in the bursal tissue was inactivated with phenol but not with ethanol or the unknown chemicals in FTA card. These results show that ordinary papers sustain the viral RNA, as does FTA card, but phenol fixation is superior to FTA card in inactivating IBDV. The new sampling method using ordinary paper with phenol fixation is safe, inexpensive, simple, and easy, and is thus suitable for conducting a global survey of IBD even where laboratory resources are limited. This practical method should contribute to the control of IBD worldwide. PMID- 17274295 TI - Genetic and pathogenic characterization of H6N1 avian influenza viruses isolated in Taiwan between 1972 and 2005. AB - This article reports the genetic and pathogenic characteristics of 34 isolates of H6N1 avian influenza viruses isolated in Taiwan between 1972 and 2005. Genetic analyses showed that a unique lineage of H6N1 viruses has been established in domestic chickens in Taiwan since 1997, and this lineage of viruses differs from the H6N1 viruses circulating in Hong Kong and Southeastern China. Pathogenicity tests showed that all Taiwanese H6N1 viruses were of low pathogenicity but might lead to economic loss when associated with other diseases. Hemagglutination inhibition tests showed that antigenic drift has occurred in Taiwanese H6N1 viruses, and sequence comparison has identified a total of five possible antigenic sites on the hemagglutinin molecule of the H6N1 viruses. Some Taiwanese H6N 1 viruses could replicate in mice without preadaptation, indicating that these viruses have the potential to cause cross-species infection into mammals. PMID- 17274296 TI - Molecular and biological characterization of a naturally occurring recombinant subgroup B avian leukosis virus with a subgroup J-like long terminal repeat. AB - Infection of broiler chickens with subgroup J avian leukosis virus (ALV) results in the induction of myeloid tumors. However, although egg-type chickens are susceptible to infection with ALV-J, the tumor incidence is very low, and on rare occasions the tumors observed are of the myeloid lineage. We recently described the isolation of an ALV (AF115-4) from commercial egg-type chickens suffering from myeloid leukosis. AF115-4 was initially identified as an ALV-J isolate based on PCR analysis of the long terminal repeat (LTR). However, further characterization of the viral envelope indicated that the virus is recombinant with subgroups B envelope and J LTR. Here we further characterize this recombinant virus at both the molecular and biological levels. We show that the AF115-4 isolate expresses a recombinant envelope glycoprotein encoded by a subgroup B gp85 region and a subgroup E gp37 region. The host range ofAF115-4 was analyzed using cells resistant to infection by subgroups A/B, J, or E; this shows that no ALV-J was present in the isolates obtained from the affected chickens. Additional antigenic characterization of AF115-4 using chicken sera specific for subgroups B or J indicated that no ALV-J was present in the samples examined. Inoculation of AF 115-4 into ALV-susceptible 1515 X 71 chickens resulted in the induction of lymphoid leukosis but not the expected myeloid leukosis affecting the commercial chickens. These results suggest that differences in the genetic makeup of the chickens from which AF115-4 was isolated and the line 1515 X 71 used in the present experiments may be responsible for the observed differences in pathogenicity. In addition, the results suggest that ALV-J continues to evolve by recombination, generating new viruses with different pathological properties. PMID- 17274297 TI - Protective immunity enhanced by chimeric DNA prime-protein booster strategy against Eimeria tenella challenge. AB - In an attempt to investigate the immune efficacy ofa DNA prime-protein booster strategy against avian coccidiosis with a chimeric construct, the Eimeria tenella antigen gene (3-1E) and chicken interferon gamma gene (ChIFN-gamma) were subcloned into the mammalian expression vector proVAX forming the plasmids proE and prol, and then linked by splicing overlap extension by polymerase chain reaction to construct the chimeric plasmid prolE; the chimeric protein (rlE) was expressed in Escherichia coli harboring the constructed plasmid pGEX/IE. Broilers were administered two intramuscular injections with the constructed DNA vaccines (50 microg); in the protein booster groups 100 microg of the rlE were given following the proIE prime. After challenge the proIE-vaccinated chickens showed the protective immunity as demonstrated by significantly reduced oocyst shedding compared with chickens immunized with proE, but the prolE vaccine did not have an additive effect of increasing antibody titer and body weight gain. The chickens in the rlE booster groups had significantly higher specific antibody responses than those immunized with prolE, and displayed further decreased oocyst shedding and increased body weight gain. Taken together, these results indicate that ChIFN gamma exerts an adjuvant effect coexpressed with 3-1E and provide the first evidence that the DNA prime-protein booster strategy is able to augment the protective efficacy of chimeric DNA vaccine against challenge with Eimeria tenella. PMID- 17274299 TI - Epididymal stone formation and decreased sperm production in roosters vaccinated with a killed strain of avian infectious bronchitis virus. AB - Our objective was to determine if vaccination with killed avian infectious bronchitis virus (AIBV) causes epididymal calcium stones in the rooster as is seen following vaccination with live attenuated AIBV. Specific-pathogen-free roosters were divided into three groups: nonvaccinated (NONVAC), live attenuated AIBV-vaccinated (LVAC), and killed AIBV-vaccinated (KVAC) groups. Roosters were vaccinated at 2, 6, 10, and 14 wk of age and the epididymal region was observed at 27 wk of age. Epididymal stones were present in 13% of NONVAC, 50% of KVAC, and 64% of LVAC roosters. Histologically, immune cells were seen in the interstitium of efferent ductules containing stones. We conclude that use of a killed vaccine does not reduce the incidence of epididymal stones. PMID- 17274298 TI - Effect of cytolethal distending toxin of Campylobacter jejuni on adhesion and internalization in cultured cells and in colonization of the chicken gut. AB - Campylobacter jejuni produces cytolethal distending toxin (CDT) that causes host cells to arrest during their cell cycle and that is involved in the pathogenesis of inflammatory diarrhea in humans. To assess the role of CDT in adherence and invasion of different cultured host cells (HeLa and HD-11) and in colonization of the chicken intestine, the genes of C jejuni NCTC11168 encoding the toxin subunits (cdtA, cdtB, and cdtC) were inactivated by insertional mutagenesis. No significant difference was found in adhesion of the wild-type C. jejuni and the isogenic mutants to HeLa and HD-11 cells. All of the mutants exhibited a decrease (>10-fold) in the ability to invade HeLa cells, but no significant difference was noticed for HD-11 cells. The ability of mutants to colonize birds either directly or by horizontal transfer was unchanged. These data indicated that although the production of cytotoxin does not play a role in the adherence to either human or avian cells, it may play a role in the invasion, survival, or both of C. jejuni in human cells, which are more susceptible to C. jejuni internalization. The CDT also does not seem to play a role in the colonization of poultry. PMID- 17274300 TI - Characterization of a strain of Eimeria meleagridis from the turkey. AB - An isolate of Eimeria meleagridis Tyzzer, 1927 was obtained by harvesting oocysts from the ceca of a turkey from northwest Arkansas and a pure line was established by infecting birds with a single oocyst. Oocysts were first produced in the ceca of infected birds from 102 to 108 hr after inoculation and were of similar size (mean length X width, 24.9 X 17.0 microm) to those of Eimeria adenoeides Moore and Brown, 1951 and Eimeria gallopavonis Hawkins, 1952. The line was identified as E. meleagridis based upon the development of large schizonts in the midintestine, and small schizonts in the ceca. Two generations of large schizonts were found 48 and 72 hr after infection, and at least two generations of small schizonts were found from 60 to 108 hr after infection. An inoculum of 2 X 10(5) oocysts was found to cause a significant reduction in weight gain from days 0-3 and 0-6 after infection, suggesting that the significance of this species of Eimeria as a pathogen of turkeys should be reassessed. PMID- 17274301 TI - Separating Mycoplasma gallisepticum field strains from nonpathogenic avian mycoplasmas. AB - Mycoplasma gallisepticum (MG) has repeatedly emerged as a serious problem in U.S. broiler, layer, and turkey industries. Tracing the source of an outbreak is essential if MG control is to be accomplished. Amplified fragment length polymorphism (AFLP), random amplification of polymorphic DNA (RAPD), and restriction fragment length polymorphism (RFLP) are valuable tools used to study MG epidemiology, allowing diagnosticians to determine the source of MG infections. In some past outbreaks, AFLP, RAPD, and RFLP fingerprinting, which require pure MG cultures, were not successful because of contaminating nonpathogenic mycoplasmas from field samples. The objective of this research was to develop a method to separate rapidly growing nonpathogenic avian mycoplasma species from slower-growing MG field strains. Mixtures of MG and three separate nonpathogenic avian mycoplasmas were inoculated onto chick embryo fibroblasts cells (CEF) allowing MG to penetrate the CEF cells. Later, gentamicin sulphate was added to the culture, eliminating the nonpathogenic mycoplasmas and allowing MG to be isolated in pure culture. Mixtures of Mycoplasma synoviae (MS) and MG could not be separated in this assay. However, removal of nicotinamide adenine dinucleotide and cysteine hydrochloride during serial passage in Frey broth medium successfully eliminated growth of MS. PMID- 17274302 TI - Effects of probiotics and maternal vaccination on Salmonella enteritidis infection in broiler chicks. AB - The effects of probiotics and maternal vaccination with an inactivated Salmonella Enteritidis (SE) vaccine on day-old chicks challenged with SE were evaluated. A 2 X 3 factorial arrangement was used (with or without probiotics; breeders nonvaccinated, vaccinated intramuscularly, or vaccinated intraperitoneally). Three trials were conducted in isolation cabinets and SE challenge was different between trials. The number of SE organisms per chick and the time interval between housing and introduction of seeder birds (hereafter called challenge) were 1.6 X 10(8) and 1 hr (Trial I), 1.8 X 10(6) and 12 hr (Trial II), and 1.2 X 10(4) and 24 hr (Trial III). SE recovery was assessed in ceca and liver at 3, 5, and 7 days postchallenge, and the number of colony-forming units (CFU) in ceca was evaluated at 5 and 7 days postchallenge. The number of SE (log CFU) in the ceca reduced 0.56 log (from 7.59 to 7.03) and 1.45 log (7.62 to 6.17) because of the treatment with probiotics in Trials II and III, respectively. The greater reduction in Trial III indicates the importance of the early use of probiotics on the prevention of SE infection. Treatment with probiotics resulted in a smaller number of SE-positive livers after 5 days postchallenge on Trial III. Although there was no significant effect of maternal vaccination on the number of SE CFU in the ceca, a significant effect of maternal vaccination on the SE CFU was observed in the liver, but not in the ceca at 5 days after challenge. PMID- 17274303 TI - Experimental infection of Attwater's/greater prairie chicken hybrids with the reticuloendotheliosis virus. AB - Reticuloendotheliosis virus (REV), a common pathogen of poultry, has been associated with runting and neoplasia in an endangered subspecies of grouse, the Attwater's prairie chicken. The pathogenesis of REV infection was examined in experimentally infected prairie chickens. Three groups of four Attwater's/greater prairie chicken hybrids were infected intravenously with varying doses (tissue culture infective dose [TCID50], 200, 1000, and 5000) of a prairie chicken isolated REV. A fourth group of four birds was not infected. Blood was collected prior to infection, and at various times up to 37 wk following infection. Peripheral blood mononuclear cells were examined for integrated proviral DNA by a single-amplification polymerase chain reaction (PCR) and nested PCR of a region within the pol gene. The nested PCR identified REV proviral DNA in all REV inoculated birds by 2 wk postinfection and confirmed chronic infection throughout the study. With the exception of a bird that died from bacterial pneumonia 8 wk postinfection, neoplasia, resembling that seen in naturally occurring infections, was observed in all birds, even those receiving as little as 200 TCID50 of virus. PMID- 17274304 TI - Tissue tropism of Helicobacter pullorum in specific pathogen-free chickens determined by culture and nucleic acid detection. AB - Three-day-old specific pathogen-free chickens (n = 24) located in isolators were inoculated orally with Helicobacter pullorum. One group (n = 12) was infected with a H. pullorum field isolate from human origin, another one (n = 12) with the American Type Culture Collection H. pullorum reference isolate 51801 originating from chickens. Both isolates were positive for cytolethal distending toxin, investigated using a polymerase chain reaction (PCR). A third group (n = 4) was kept as a negative control. Starting on day 7 of life, birds from each group were euthanatized at different time points up to 35 days. Various organ samples were taken aseptically and processed by culture and a H. pullorum-specific PCR. In the group infected with the human isolate the nucleic acid of H. pullorum was detected in the caecal tonsils and caeca of 12 and 11 birds, respectively. Live bacteria were cultivated from the caecal tonsils and caeca of five birds 24 and 31 days postinfection. Live bacteria were also isolated from the heart of one bird, whereas PCR had to be used to detect the nucleic acid of H. pullorum in the gallbladder of four birds. No live bacteria were reisolated at any time from birds infected with the avian isolate, but bacterial nucleic acid was detected in the caeca of five birds and in the gallbladder of one. In both groups neither live H. pullorum nor its nucleic acid were detected in the liver, spleen, and duodenum. Compared to the avian H. pullorum isolate the human isolate proved to be more invasive. No obvious clinical symptoms or disease was seen in the chickens during the entire experiment. The reisolation of live bacteria at the end of the experiments indicates that H. pullorum could enter the food chain even after early infection in birds. Furthermore, PCR was demonstrated to be helpful in tracing these fastidious bacteria. PMID- 17274305 TI - Detection of very virulent strains of infectious bursal disease virus (vvIBDV) in commercial broilers from Uruguay. AB - Bursal samples were collected from commercial broiler flocks exhibiting clinical signs suggestive of infectious bursal disease (IBD). The presence of IBD virus (IBDV) was confirmed by partial amplification of the VP2 and VP1 genes by reverse transcription and polymerase chain reaction. The Uruguayan viruses were identified as very virulent strains of IBDV (vvIBDV) by nucleotide and amino acid sequence analysis. The comparison of the VP2 nucleotide sequences among the Uruguayan samples revealed the presence of single-nucleotide polymorphisms suggestive of different viral subpopulations or quasispecies in the same flock. The comparative analysis indicated that these Uruguayan viruses were genetically close to the European strain UK661 and to the vvIBDVs previously detected in Venezuela. Our analyses provided new information about the distribution, variability, and evolutionary trends of vvIBDV strains in the Americas. PMID- 17274306 TI - Improved polymerase chain reaction technique for determining the species composition of Eimeria in poultry litter. AB - An improved polymerase chain reaction (PCR)-based method for determining the species composition of Eimeria in poultry litter was developed by incorporating species-specific internal standards in the assay. Internal standard molecules were prepared by fusing seven different Eimeria species-specific intervening transcribed sequence 1 (ITS1) rDNA primer pairs to a non-Eimeria DNA molecule and by cloning the hybrid DNA molecules into a plasmid. The internal DNA standards were then used in Eimeria-specific ITS 1 PCR, and they were found to be capable of detecting E. acervulina, E. maxima, E. praecox, and E. tenella oocysts isolated directly from poultry litter. PMID- 17274307 TI - Characterization of pigeon-origin Newcastle disease virus isolated in China. AB - Fourteen pigeon-origin Newcastle disease virus (NDV) isolates were obtained from sick pigeons in China between 1996 and 2005. The mean death time (MDT) of embryonated eggs and the intracerebral pathogenicity indices (ICPI) were tested to determine the virulence of the field isolates. The result indicated that most isolates were proved to be mesogenic (MDT 60-90 hr and ICPI > 1.2). The main function regions of F protein gene of the isolates were amplified and sequenced for phylogenetic and residue substitutive analysis. The fusion protein cleavage site sequences of most isolates had multiple basic amino acids R/KRQKRF at positions 112-116 and a phenyl alanine at position 117, characteristic of velogenic isolates. In the phylogenetic tree, the majority of the isolates were clustered into a single genetic lineage, termed genotype VIb, and were typical pigeon paramyxovirus type 1, whereas a small number of recent isolates (three strains) were grouped into genotype VIId, a predominant genotype responsible for most Newcastle disease outbreaks in chickens and geese since the end of last century. One isolate, PK9901, was proved to be a lentogenic strain, of genotype II NDV, to which the vaccine strain La Sota belongs. PMID- 17274308 TI - Possible human-avian transmission of Mycobacterium tuberculosis in a green-winged macaw (Ara chloroptera). AB - This report describes a case of Mycobacterium tuberculosis infection in a green winged macaw (Ara chloroptera), confirmed by microbiologic and pathologic diagnostics, and notes a possible human-avian transmission. Clinical signs included cutaneous swellings, profound leukocytosis, and signs of osteomyelitis in the long bones. Proliferation consisted of several nodules with small greenish caseous foci in cross-section and revealed a severe granulomatous inflammation with intralesional acid-fast rods. Mycobacterium tuberculosis was isolated from subcutaneous nodules and biochemically confirmed. The disease in avian species is of zoonotic importance. PMID- 17274309 TI - Hyperbaric oxygenation therapy enhances the protective effect of moderate hypothermia against forebrain ischemia in the gerbil hippocampus. AB - Moderate hypothermia may have a beneficial effect on the neurological outcome. However, ischemic deterioration such as brain swelling during rewarming has been reported as a notable complication after successful therapeutic cerebral hypothermia. In this study, we investigated the effects of hyperbaric oxygenation during rewarming. Forebrain ischemia was produced in 24 gerbils and sham ischemia in 8 animals. Then ischemia-treated animals were divided into 3 groups, whole body moderate hypothermia (31 degrees C for 60 min) and hyperbaric oxygenation (HBO2) (2- atmosphere absolute for 60 min using 100% oxygen) during rewarming group (n = 8), moderate hypothermia without HBO2 group (n = 8), and sham treatment without hypothermia and without HBO2 group (n = 8). Both the hypothermia group (77.9 +/- 48.1 neurons per mm, mean +/- SD) and hypothermia + HBO2 group (127.6 +/- 29.7 neurons per mm,) showed significant preservation of CA1 pyramidal neurons in the hippocampus compared to that in the sham treatment group (6.4 +/- 2.7) (p < 0.01). Furthermore, the hypothermia + HBO2 group showed significantly greater preservation of CA1 pyramidal neurons than the hypothermia group (p < 0.05). These results suggest that HBO2 during rewarming preserves the protective effect of hypothermia against ischemic neuronal damage. PMID- 17274310 TI - Hyperbaric oxygen pre-breathe modifies the outcome of decompression sickness. AB - Deep sea divers, aviators and astronauts are at risk of decompression sickness when the ambient pressure reductions exceed a critical threshold. Venous bubbles associated with decompression sickness have the potential to react with the vascular membrane and adjacent blood products, eliciting an inflammatory cascade. Preventive measures usually involve careful decompression procedures to avoid or reduce bubble formation. De-nitrogenation with 100% oxygen pre-breathing as a preventive measure has been well established at least in altitude decompression exposures. The objective of this study was to determine the physiological and biochemical effects of Hyperbaric Oxygen Pre-breathe (HBOP) upon decompression from a hyperbaric exposure. Male Sprague-Dawley rats were randomly assigned to one of eight groups. Two experimental groups received HBOP at 1 and 18 hours prior to decompression, as compared with ground level oxygen or non-treated groups that still experienced decompression stress, and the associated non decompressed controls. The results showed decreased extravascular lung water (pulmonary edema), bronchoalveolar lavage and pleural protein and arterial, broncho-alveolar lavage, and urine leukotriene E4 (LKE4) levels in both the 1Hr and 18Hr HBOP decompressed rats compared to non-oxygenated decompressed rats, as well as a decreased overall expression of signs of decompression sickness. This study indicates that HBOP-treated rats exhibit fewer signs and complications of decompression sickness compared with non-treated or ground level oxygen treated rats. PMID- 17274311 TI - Health and efficiency in trimix versus air breathing in compressed air workers. AB - The Western Scheldt Tunneling Project in the Netherlands provided a unique opportunity to evaluate the effects of trimix usage on the health of compressed air workers and the efficiency of the project. Data analysis addressed 318 exposures to compressed air at 3.9-4.4 bar gauge and 52 exposures to trimix (25% oxygen, 25% helium, and 50% nitrogen) at 4.6-4.8 bar gauge. Results revealed three incidents of decompression sickness all of which involved the use of compressed air. During exposure to compressed air, the effects of nitrogen narcosis were manifested in operational errors and increased fatigue among the workers. When using trimix, less effort was required for breathing, and mandatory decompression times for stays of a specific duration and maximum depth were considerably shorter. We conclude that it might be rational--for both medical and operational reasons--to use breathing gases with lower nitrogen fractions (e.g., trimix) for deep-caisson work at pressures exceeding 3 bar gauge, although definitive studies are needed. PMID- 17274312 TI - Hyperbaric oxygen (HBO2) in tinnitus: influence of psychological factors on treatment results? AB - HBO2 for subjective tinnitus has never been objectified, yet it is still advocated by many institutions. We analyzed the therapeutic effect of HBO2 treatment in the context of accompanying factors, especially focusing on the patients' attitude towards HBO2 prior to therapy. METHODS: 360 patients suffering from tinnitus were investigated in this study. They were randomized into 2 hyperbaric treatment protocols, one at 2.2, the other at 2.5 bar, 60 min bottom time each. All patients were asked to fill in a questionnaire (social and medical history, tinnitus characteristics, pre-HBO2 duration oftinnitus, prior therapy, pre-treatment expectation, accompanying symptoms) immediately before and one month after HBO2 treatment. The subjective impact of tinnitus on daily life was assessed using a score from 1 to 10 prior to HBO2 and one month after the treatment. RESULTS: 12 patients (3.3%) experienced complete remission of tinnitus, in 122 (33.9%) the intensity lessened, and 44 (12.2%) had a subjectively agreeable change of noise characteristics. 157 (43.6%) stated no change and 25 (6.9%) experienced deterioration. There was no statistically significant difference between the two hyperbaric protocols (p > 0.05). Out of 68 patients with positive expectation towards HBO2 therapy 60.3% stated that the tinnitus had improved whereas out of the patients who underwent therapy with indifferent (N = 271) or negative expectations (N = 21) only 47.2% and 19%, respectively, reported an improvement. The influence of both positive and negative anticipation on the outcome was statistically significant (p < 0.05). CONCLUSION: The therapeutic effects of HBO2 on subjective tinnitus might be greatly due to psychological mechanisms triggered by the attitude of the patient towards HBO2 therapy prior to the treatment. PMID- 17274313 TI - Epidemiology of severe carbon monoxide poisoning in children. AB - OBJECTIVE: To describe the characteristics of severe pediatric CO poisoning cases treated with hyperbaric oxygen (HBO2) to determine key features that might aid prevention efforts. DESIGN: Using data on 250 consecutive children treated with HBO2 for CO poisoning at Virginia Mason Medical Center in Seattle, we calculated descriptive statistics and used Fisher's Exact test to determine differences in case frequency of CO sources with respect to race/ethnicity. RESULTS: There were 236 (94%) unintentional and 14 (6%) intentional poisonings. Loss of consciousness occurred in 50%. The average initial carboxyhemoglobin level was 19.0 +/- 10.3% (mean +/- SD; range 0.3% to 57.6%). Months with the highest proportion of incidents were November (15%), December (12%) and January (14%). Children 0-2 years old were most often poisoned by charcoal briquettes (40%), in contrast to older children who were most often poisoned by motor vehicle. Females were most often poisoned by charcoal briquettes (28%), in contrast to males in which motor vehicle exhaust predominated (41%). Minorities were disproportionately affected by CO poisoning compared with non-Latino whites (P < 0.001). Overall, motor vehicle exhaust predominated for Non-Latino whites (33%), while Non-Latino blacks (55%) and Latinos (71%) had significantly higher proportions of poisonings by charcoal briquettes (P < 0.001). All intentional cases occurred in adolescents aged 15 to 17 years, 71% of these in males, mostly by motor vehicle exhaust (79%). CONCLUSIONS: Severe pediatric CO poisoning demonstrates a seasonal pattern with key sources of exposure varying by gender, age, and race/ethnicity. Minorities are at increased risk for severe CO poisoning. Intentional CO poisoning occurs primarily among adolescent males and by motor vehicle exhaust. Prevention efforts should take these factors into consideration. PMID- 17274314 TI - Effects of respiratory muscle training on respiratory CO2 sensitivity in SCUBA divers. AB - Typically, ventilation is tightly matched to CO2 production. However, in some cases CO2 is retained (SCUBA diving). One factor behind hypoventilation in divers may be low respiratory CO2 sensitivity. If this is due to inadequate respiratory muscle performance it might be remedied by respiratory muscle training (RMT). We retrospectively investigated respiratory CO2 sensitivity prior to and after RMT in several groups of SCUBA divers. CO2 sensitivity (slope of expired ventilation as a function of inspired PCO2) was measured with a rebreathing technique in 35 subjects with diving experience. RMT consisted of either isocapnic hyperventilation or intermittent vital capacity breaths (twice/minute) against spring loaded breathing valves imposing static and resistive loads generating average inspiratory pressures of approximately 40 cmH2O and expiratory pressures of approximately 47 cmH2O; RMT was performed 30 min/day, 3 or 5 days/week for 4 weeks. Based on pre-RMT CO2 sensitivity the subjects were divided into three groups: low sensitivity: < 2 l/min/mmHg PCO2, normal: 2-4 l/min/mmHg, and high sensitivity: > 4 l/min/mmHg of inspired PCO2. The normal group had a Pre-RMT CO2 sensitivity of 2.88 +/- 0.60 and a post RMT sensitivity of 2.51 +/- 0.88 l/min/mmHg (Mean +/- SD, n = 19, p = n.s). Response in low sensitivity subjects increased from 1.41 +/- 0.32 to 2.27 +/- 0.53 (n = 10, p = 0.002,) while in the high sensitivity group it decreased from 5.41 +/- 1.25 to 2.90 +/- 0.32 l/min/mmHg (n = 6, p = 0.003). These preliminary findings showed that 46% of the subjects had abnormal sensitivity, and suggest that RMT may normalize it in hypo- and hyper-ventilating divers. If the present results are verified, RMT may be an effective means of enhancing safety in CO2 retaining divers. PMID- 17274315 TI - Negative pressure oxygen breathing and head-down tilt increase nitrogen elimination. AB - Negative pressure breathing (NPB) increases the rate of nitrogen elimination, which is thought to be due to an increase in cardiac output due to augmented venous return to the heart. Hyperoxia, however, decreases the rate of nitrogen elimination. The effect of hyperoxia on the increase in nitrogen elimination during NPB is not known. We hypothesized that NPB as and head down tilt (HDT), which is also thought to increase cardiac output, would counteract the detrimental effects of hyperoxia on nitrogen elimination. Nitrogen elimination was measured in 12 subjects while they lay supine breathing 100% O2 supplied at atmospheric pressure (control), -10 cm H2O (NPOB(-10)), and -15 cm H2O (NPOB( 15)). Nitrogen elimination was also measured in the subjects while they breathed 100% O2 supplied at atmospheric pressure in the supine position with a 6 degrees HDT. Over a two-hour washout period, NPOB significantly increased nitrogen elimination by more than 14%, although there was no significant difference between NPOB(-10) and NPOB(-15). HDT also significantly increased nitrogen elimination by almost 8%. Neither NPOB nor HDT significantly affected cardiac output but calf blood flow was significantly lower during NOPB(-15). Combining NPB or HDT with 100% oxygen breathing appear to be useful means of increasing nitrogen elimination and should be considered in situations where this effect may be beneficial, such as with oxygen prebreathing prior to decompression. PMID- 17274317 TI - Hyperbaric oxygen therapy: a high-risk procedure? An update II. PMID- 17274318 TI - The standard of care is the same for all dentists. PMID- 17274316 TI - Alveolar gas composition before and after maximal breath-holds in competitive divers. AB - The urge to breathe, as stimulated by hypercapnia, is generally considered to cause a breath-hold diver to end the breath-hold, and pre-breath hold hyperventilation has been suggested to cause hypoxic loss of consciousness (LOC) due to the reduced urge to breathe. Competitors hyperventilate before "Static Apnea", yet only 10% surface with symptoms of hypoxia such as loss of motor control (LMC) or LOC. We hypothesized that the extensive hyperventilation would prevent hypercapnia even during prolonged breath-holding and we also recorded breaking-point end-tidal PO2 in humans. Nine breath-hold divers performed breath holds of maximal duration according to their chosen "Static Apnea" procedure. They floated face down in a swimming pool (28 degrees C). The only non-standard procedure was that they exhaled into a sampling tube for end-expiratory air, before starting the breath-hold and before resuming breathing. Breath-hold duration was 284 +/- 25 (SD) seconds. End-tidal PCO2 was 18.9 +/- 2.0 mmHg before apnea and 38.3 +/- 4.7 mmHg at apnea termination. End-tidal PO2 was 131.7 +/- 2.7 mmHg before apnea and 26.9 +/- 7.5 mmHg at apnea termination. Two of the subjects showed LMC after exhaling into the sampling tube; their end-tidal PAO2 values were 19.6 and 21.0 mmHg, respectively. End-tidal CO2 was normocapnic or hypocapnic at the termination of breath-holds. These data suggest that the athletes rely primarily on the hypoxic stimuli, probably in interaction with CO2 stimuli to determine when to end breath-holds. The severity of hypoxia close to LOC was similar to that reported for acute hypobaric hypoxia in humans. PMID- 17274319 TI - My office manager, the alcoholic. PMID- 17274320 TI - Do you know your employees' real cost per hour? PMID- 17274321 TI - Requests for X-rays and other documentation for claims. PMID- 17274323 TI - A salute to Gerri Cherney, retiring MDA executive director. Interview by Jeffery Johnston. PMID- 17274322 TI - Why obese people believe they are eating "healthy". PMID- 17274324 TI - Living with addiction is risky; getting help shouldn't be. PMID- 17274325 TI - 'I'm a dentist and a recovering drug addict". PMID- 17274326 TI - What are the warning signs of alcoholism? The NCADD self-test. PMID- 17274327 TI - Use of optical coherence tomography in pediatric ophthalmology. PMID- 17274329 TI - Maculopathy in Pierre Robin sequences. PMID- 17274328 TI - What's your diagnosis? Hamartoma of the retinal pigment epithelium. PMID- 17274330 TI - Retinal detachments in the pediatric population: part I. PMID- 17274331 TI - Preschool vision screening by family physicians. AB - PURPOSE: To determine the rate of preschool vision screening in family practice. To evaluate attitudes and beliefs about the importance of, and barriers to, preschool vision screening. METHOD: Mail survey of a national sample of family physicians. RESULTS: The response rate was 35% (237 of 671 eligible respondents). Most (90%) considered preschool vision screening important. The majority (91%) included some component of the eye examination as part of their routine well child care for preschool-aged children. The likelihood of formal screening increased with age (3 years, 36%; 4 years, 58%; 5 years, 73%; P < .01). Most (88%) used a wall chart to test for visual acuity. Stereoacuity was rarely (7%) tested. Barriers included the perception that children are uncooperative (39%) and that screening is too time-consuming (21%). Fifty-nine percent would only consider using a vision screening test if its false-positive rate was 10% or less. Some (26%) reported that all children should be examined by an optometrist or ophthalmologist prior to school entry, regardless of any screening. CONCLUSIONS: The rate of screening by family physicians is similar to that by pediatricians. Providing education regarding optimal vision screening strategies and expected outcomes of screening may be important for improving both the rate and the quality of preschool vision screening. Ophthalmologists may play an important role in this process through the feedback they provide to referring physicians. PMID- 17274332 TI - Immunosuppressants used in a steroid-sparing strategy for childhood uveitis. AB - PURPOSE: To review, with respect to etiology, the efficacy and complications of different immunosuppressants used in a steroid-sparing strategy for children with uveitis. PATIENTS AND METHODS: Forty children with uveitis were observed during a 5-year period, from 1997 to 2002. After complete ocular and physical assessment, routine and specific laboratory investigations were conducted along with radiologic examination. All cases underwent local therapy. Systemic corticosteroids were necessary in 75% of cases. Pediatric staff determined the need for initial association or sequential relay with immunosuppressants, depending on the severity of the uveitis. A steroid-sparing strategy was developed. RESULTS: The average age was 6.5 years (range, 3 months to 14 years), with a male-to-female ratio of 23 to 17. Uveitis was anterior in 55% of cases, intermediate in 2.5%, posterior in 42.5%, and bilateral in 62.5%. A positive etiology was found in 47.5% of cases, and articular symptoms were present in 25%. Overall, the improvement in visual acuity was 62.2%. Where corticotherapy was associated with azathioprine, a 61% improvement was achieved. Corticosteroid therapy associated with mycophenolate mofetil resulted in a 94% improvement. No complications were present in 42.5% of cases. Ocular complications were present in 57.5% of cases and systemic complications were present in 12.5% of cases, none being directly related to the use of steroids. CONCLUSION: The association of systemic corticotherapy and immunosuppressants in pediatric relapsing or steroid dependent uveitis allows good recovery of visual acuity, fewer complications, and a minimization of side effects, especially those related to systemic corticosteroids. It requires close collaboration between the ophthalmologist and a fully involved pediatrician. PMID- 17274333 TI - Releasable conjunctival suture for adjustable suture surgery. AB - BACKGROUND: Adjustable sutures are widely used in adult strabismus surgery, with a second procedure performed to close the conjunctiva irrespective of whether adjustment is required. We describe a technique where the conjunctiva is closed using a buried releasable suture, eliminating the second procedure if adjustment is deemed unnecessary. METHOD: The conjunctiva is closed using a 6/0 absorbable polyglactin 910 releasable suture. It is tied in a bow, like the muscle sutures, and tucked under the conjunctiva. If adjustment is not required, the eye does not need to be touched because the conjunctiva is secured by the suture. If adjustment is required, it is easy to untie the conjunctival suture, allowing good exposure to the underlying muscle sutures. RESULTS: In our prospective series of 30 patients, we found our technique effective and patient friendly. Patients had at least 3 months of follow-up with no significant complications. CONCLUSIONS: This technique is acceptable, accessible, and time saving for both surgeons and patients. It is especially useful for anxious patients and adolescents, for whom postoperative manipulation can be difficult, and for cases where the probability of adjustment is low. PMID- 17274334 TI - Ultrasonographic findings in eyes with retinal detachments secondary to retinopathy of prematurity. AB - PURPOSE: To describe ultrasonographic findings of stages 4 and 5 retinopathy of prematurity. PATIENTS AND METHODS: Ocular ultrasonography was performed using a 10-MHz transducer. Forty-four patients (88 eyes) with stages 4 and 5 retinopathy of prematurity were evaluated. Twenty-five patients were female. The mean age was 8.4 months (standard deviation, +/- 4.9). RESULTS: Retinal detachment configurations were as follows: 31% closed posterior and open anterior, 19% closed posterior and anterior, 14% open posterior and anterior, and 14% open posterior and closed anterior. Additional findings included vitreous opacities (14%), proliferative vitreoretinopathy (22%), subretinal opacities (24%), choroidal thickening (18%), and reduced axial diameter (75%). CONCLUSIONS: Ultrasonographic evaluation in eyes with advanced retinopathy of prematurity guides surgical indication, management, and visual prognosis. PMID- 17274335 TI - Trypan blue-assisted posterior tenectomy of the superior oblique. AB - Posterior tenectomy of the superior oblique tendon can be difficult, particularly for inexperienced surgeons, due to problems in visualization and anatomic peculiarities. Trypan blue can be used to stain the superior oblique tendon for easy identification and delineation of it at its insertion, making the current surgical technique less difficult. PMID- 17274336 TI - Anterior segment epibulbar choristoma containing brain tissue and with aphakia. AB - We report an unusual case of an epibulbar choristoma in a neonate born with a mass arising from the cornea. Radiologic examination showed focal corneal bulge with absence of the lens. Histologic study revealed the lesion was an epibulbar choristoma composed of only brain tissue. PMID- 17274337 TI - Isolated large limbal nodule as the presenting feature of vernal keratoconjunctivitis. AB - The presentation of vernal keratoconjunctivitis ranges from mild itching to severe corneal involvement. This case highlights an isolated limbal nodule as an unusual presentation of vernal keratoconjunctivitis that did not respond to topical fluorometholone (0.1%), but resolved with topical cyclosporine (2%). Topical cyclosporine (2%) can be considered first-line treatment for such cases. PMID- 17274339 TI - Arachnoid cyst resulting in sixth nerve palsy in a child. AB - A 2 year old presented with incomitant esotropia and abduction deficit consistent with sixth nerve palsy. Neuroimaging revealed an arachnoid cyst on the left. Neurosurgical shunting followed by strabismus surgery relieved the abduction deficit and esotropia. An arachnoid cyst may be a rare cause of acquired sixth nerve palsy and strabismus in children. PMID- 17274340 TI - Unifocal, subconjunctival twin cysticercosis cysts. AB - We report a case of multiple, unifocal, subconjunctival cysticercosis in an 8 year-old boy. Two cysts, each with a scolex, were in the subconjunctival space. They were removed surgically, and histopathologically proven to be Cysticercus cellulosae. This is only the second report of twin cysticercus in the literature, to the best of our knowledge. PMID- 17274338 TI - Restrictive strabismus in Parry-Romberg syndrome. AB - Forced duction and generation testing of a patient with Parry-Romberg syndrome (progressive hemifacial atrophy) confirmed that his incomitant hypotropia and esotropia were restrictive and not due to nerve paresis. This suggests that an orbital inflammatory process (causing extraocular muscle fibrosis) is part of this rare and poorly understood syndrome. PMID- 17274341 TI - Bilateral extensive persistent pupillary membranes. AB - We examined a 14-year-old girl with bilateral hyperplastic persistent pupillary membranes, present since birth, with poor visual acuity. The membranes were excised surgically; visual acuity improved. Extensive persistent pupillary membranes can be removed safely by surgical methods if they are large enough to obscure the pupillary axis and affect visual acuity. PMID- 17274342 TI - Familial ectopia lentis with Axenfeld-Rieger anomaly. AB - Three siblings with ectopia lentis were examined for associated abnormalities. Case 1 had Axenfeld-Rieger anomaly and retinal detachment. Case 2 had Axenfeld Rieger anomaly, ciliary staphyloma, and glaucoma. Case 3 had no associated ocular abnormality. The parents had normal eyesight. This is the first report of ectopia lentis associated with Axenfeld-Rieger anomaly. The mode of inheritance is likely autosomal recessive. PMID- 17274343 TI - Floppy anomalous superior oblique muscle tendon. PMID- 17274344 TI - A quest for a magical approach to physician relations: overcome major barriers to a successful sales program. PMID- 17274345 TI - Use call centers to ensure accountability, demonstrate ROI. PMID- 17274346 TI - Evaluation of a syndromic surveillance system using the WSARE algorithm for early detection of an unusual, localized summer outbreak of influenza B: implications for bioterrorism surveillance. AB - BACKGROUND: Syndromic surveillance systems have been developed for early detection of bioterrorist attacks, but few validation studies exist for these systems and their efficacy has been questioned. OBJECTIVES: To assess the capabilities of a syndromic surveillance system based on community clinics in conjunction with the WSARE algorithm in identifying early signals of a localized unusual influenza outbreak. METHODS: This retrospective study used data on a documented influenza B outbreak in an elementary school in central Israel. The WSARE algorithm for anomalous pattern detection was applied to individual records of daily patient visits to clinics of one of the four health management organizations in the country. RESULTS: Two successive significant anomalies were detected in the HMO's data set that could signal the influenza outbreak. If data were available for analysis in real time, the first anomaly could be detected on day 3 of the outbreak, 1 day after the school principal reported the outbreak to the public health authorities. CONCLUSIONS: Early detection is difficult in this type of fast-developing institutionalized outbreak. However, the information derived from WSARE could help define the outbreak in terms of time, place and the population at risk. PMID- 17274347 TI - Pre-hypertension is a common phenomenon: national database study. AB - BACKGROUND: Recently the Joint National Committee (7th report) introduced the term "pre-hypertension." Little is known on its prevalence in the general population. OBJECTIVES: To assess the prevalence of pre-hypertension in a large national cohort. METHODS: We analyzed the database of all > or = 18 year old members of Leumit Health Services, one of the four health management organizations in Israel, from which we retrieved the recorded blood pressure levels. Pre-hypertension was defined according to the JNC-7 criteria. RESULTS: Of the 426,033 subjects 18.6% had a diagnosis of hypertension or used antihypertensive medications. Only 40.8% of the other 346,799 subjects had had their BP measured in the preceding 2 years. BP recording rates were higher in females than in males (45.1% vs. 36.3%) and higher in elderly subjects than in young subjects (56% aged 66-75 years vs. 32% aged 18-25). Pre-hypertension was observed in 80,625 (23.2%) of the 346,799 while only 56,113 (16.2%) had normal BP records. The prevalence of pre-hypertension increased with age (13.3% aged 18-25 vs. 44.8% aged 66-75), and was more prevalent in men than in women (24.0% vs. 22.5%). CONCLUSIONS: BP levels among young people are low, even though the prevalence of pre-hypertension in this population may be high. Thus, more emphasis should be given to routine BP measurements and confirmation of the findings in all age groups. PMID- 17274348 TI - Ethnic variability in warfarin maintenance in the community setting: a population based study in a managed care environment in Israel. AB - BACKGROUND: Ethnicity has been associated with variance in warfarin treatment regimens in various settings. OBJECTIVES: To determine whether ethnicity is associated with variance in patient management in Israel. METHODS: Data were extracted from the electronic patient records of Clalit Health Services clinics in the Sharon Shomron region. The study group comprised all patients treated with warfarin who performed international normalized ratio tests for at least 6 months in 2003. The proportion of tests of each patient within the target range was calculated, as was the crude average rates and 95% confidence intervals for Jewish and Arab patients. The data were then stratified by patient's gender and age, specialty of the attending physician, and the country where the physician studied medicine. RESULTS: We identified 2749 Jews and 293 Arabs who met the inclusion criteria of the study. The crude average rate of patients' INR tests within the target range was 62.3% among Jews (95% CI 61.5-63.1) and 52.7% (95% CI 49.9-55.5) among Arabs. When stratified by gender, age, and the treating physician's specialty and country of education, the stratum-specific rates among Jewish patients were consistently higher than among Arabs. CONCLUSIONS: These results suggest that cultural differences regarding adherence to recommendations for drug therapy in addition to genetic factors may be associated with this variance. PMID- 17274349 TI - Antibiotic consumption successfully reduced by a community intervention program. AB - BACKGROUND: The association between antibiotic use in the community and antimicrobial resistance is known. Attention has recently focused on the type of agents being prescribed. OBJECTIVES: To implement, evaluate and compare the efficacy of two community intervention programs--continuous versus seasonal medical education--oriented to primary care physicians with emphasis on the appropriate use of antimicrobial drugs. METHODS: From October 2000 to April 2003 we conducted two interventions: a) a monthly educational campaign in selected clinics promoting appropriate diagnosis of common infectious diseases and prudent antibiotic use (continuous intervention group); and b) a massive educational campaign, conducted before two consecutive winters, promoting the judicious use of antibiotics for treating respiratory infections (continuous intervention group and seasonal intervention group). Sixteen similar clinics were randomized (8 to each group). The total antibiotic use was measured as defined daily dose/1000 patients/day, and compared between the groups. RESULTS: The total use of antibiotics decreased between 1999-2000 and 2002-2003 in both groups, but slightly more significantly in the continuous intervention group. The DDD/1000 patients/day for the seasonal group in 1999-2000 was 27.8 vs. 23.2 in 2002-2003; and for the continuous group 28.7 in 1999-2000 vs. 22.9 in 2002-2003, a reduction of 16.5% and 20.0% respectively (P < 0.0001). The main change in antibiotic use was noted for broad-spectrum antibiotics. CONCLUSIONS: We present a successful community intervention program aimed to reduce unnecessary antibiotic use. Amplification of this type of intervention is imperative to stop the increase in antimicrobial resistance. PMID- 17274350 TI - Predicting survival with reperfusion arrhythmias during primary percutaneous coronary intervention for acute myocardial infarction. AB - BACKGROUND: The significance of arrhythmia occurring after successful recanalization of an occluded artery during treatment following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction is controversial. OBJECTIVES: To study the association of reperfusion arrhythmia with short and long-term survival. METHODS: We used a prospective registry of consecutive STEMI patients undergoing PPCI. Patients with an impaired epicardial flow (TIMI flow grade < 3) at the end of the procedure were excluded. RESULTS: Of the 688 patients in the study group, 22% were women. Mean (+/- SD) age of the cohort was 61 (+/- 14) years and frequent co-morbidities included diabetes mellitus (25%), dyslipidemia (55%), hypertension (43%) and smoking (41%). RA was recorded in 200 patients (29%). Patients with RA had lower rates of diabetes (16% vs. 30%, P < 0.01) and hypertension (48% vs. 62%, P < 0.01), and a shorter median pain-to-balloon time (201 vs. 234 minutes, P < 0.01) than patients without RA. Thirty day mortality was 3.7% and 8.3% for patients with and without RA, respectively (P = 0.04). After controlling for age, gender and pain-to-balloon time the hazard ratio for mortality for patients with RA during a median follow up period of 466 days was 0.46 (95% confidence interval 0.23-0.92). CONCLUSIONS: The occurrence of RA immediately following PPCI for acute STEMI is associated with better clinical characteristics and identifies a subgroup with a particularly favorable prognosis. PMID- 17274351 TI - Excessive weight gain as a possible predictor of necrotizing enterocolitis in premature infants. AB - BACKGROUND: Necrotizing enterocolitis is a common progressive gastrointestinal disease affecting more than 5% of very low birth weight infants and associated with a high mortality rate. OBJECTIVES: To determine whether excessive weight gain in preterm infants is an early sign of NEC. METHODS: Seventeen preterm infants with perforated NEC were identified and matched with 17 control subjects for birth weight and gestational age. The postnatal age (days) at diagnosis of NEC was identified, and weight changes as well as clinical and laboratory data were recorded and compared for 7 days prior through 7 days post-diagnosis. RESULTS: A significant difference in weight gain was noticed between D-1 and D 0. The NEC and control groups gained 5.1% and 1.2%, respectively (P = 0.002). None of the sick infants lost weight on days -1 to D 0. CONCLUSIONS: Excessive weight gain was observed in premature infants who subsequently developed NEC. Daily evaluation of weight changes should be considered part of a strategy for early identification of infants at risk for developing NEC. Future studies are needed to confirm this finding in a prospective manner and to investigate its pathogenesis. PMID- 17274352 TI - Treatment of femoral fractures in neonates. AB - BACKGROUND: Fractures of the femur in neonates are relatively uncommon. The infants feel pain and discomfort, causing parental distress, and the hospital stay is longer. Treatment of this specific fracture is problematic because of the small size of the baby. OBJECTIVES: To review the results of the treatment of neonatal femoral fractures. METHODS: We retrospectively reviewed all neonatal fractures of the femur during a 12 year period. Thirteen fractures of the femur in 11 babies were treated with improvised Bryant skin traction of both legs. All the patients were reexamined after a mean follow-up period of 5.2 years. RESULTS: All fractures healed satisfactorily clinically and radiographically, with no residual deformity, leg length discrepancy or functional impairment. CONCLUSIONS: Bryant's traction for 2-3 weeks in hospital is a safe method for the treatment of femoral fractures in neonates, and the outcome is good. PMID- 17274353 TI - Halofuginone reduces the occurrence of renal fibrosis in 5/6 nephrectomized rats. AB - BACKGROUND: Halofuginone is a novel antifibrotic agent that can reverse the fibrotic process by specific inhibition of collagen type I synthesis. OBJECTIVES: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/6 nephrectomy rat model METHODS: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure, proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, sirius red staining and in situ hybridization RESULTS: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen alpha1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo. CONCLUSIONS: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals. PMID- 17274354 TI - Current criteria for hip fracture risk assessment--are we missing something? AB - BACKGROUND: Hip fracture rates are increasing worldwide, and the risk for a second hip fracture is high. The decision to administer antiresorptive treatment is based mainly on bone mineral density and/or a history of previous osteoporotic fractures. OBJECTIVES: To evaluate the contribution of BMD, previous fractures, clinical and laboratory parameters to hip fracture risk assessment. METHODS: The study population included 113 consecutive hip fracture patients, aged 72.5 +/- 9.4 years, discharged from the orthopedic surgery department. BMD was assessed at the lumbar spine, femoral neck and total hip. The results were expressed in standard deviation scores as T-scores--compared to young adults and Z-scores- compared to age-matched controls. Plasma or serum levels of parathyroid hormone, 25-hydroxyvitamin 3 and urinary deoxypyridinoline cross-links were evaluated. RESULTS: We observed T-scores < or = 2.5 in 43 patients (45.3%) at the lumbar spine, in 47 (52.2%) at the femoral neck and in 33 (38%) at the total hip. Twenty eight patients (29.5%) had neither low BMD nor previous osteoporotic fractures. Using a T-score cutoff point of (-1.5) at any measurement site would put 25 (89%) of these patients into the high fracture risk group. Mean DPD level was 15.9 +/- 5.8 ng/mg (normal 4-7.3 ng/mg creatinine). Vitamin D inadequacy was observed in 99% of patients. CONCLUSIONS: Using current criteria, about one-third of elderly hip fracture patients might not have been diagnosed as being at risk. Lowering the BMD cutoff point for patients with additional risk factors may improve risk prediction yield. PMID- 17274355 TI - The genetic basis of malignant hyperthermia. PMID- 17274356 TI - Pre-hypertension: a new-old field. PMID- 17274357 TI - Chronic relapsing lupus pancreatitis. PMID- 17274358 TI - Exercise-induced homonymous quadranopsia after head trauma. PMID- 17274359 TI - Coexistence of psoriatic arthritis and systemic lupus erythematosus. PMID- 17274360 TI - Montelukast-related Churg-Strauss vasculitis presenting with peripheral neuropathy. PMID- 17274361 TI - Cogan's syndrome: a rare atypical presentation. PMID- 17274363 TI - Maimonides and the ethics of patient autonomy. PMID- 17274362 TI - Periurethral leiomyoma. PMID- 17274364 TI - Hand washing and infection control. PMID- 17274365 TI - [The feasibility and mechanism of recombinant adenovirus Ad - p 14 ARF in gene therapy of liver cancer]. AB - OBJECTIVE: To explore the feasibility and mechanism of recombinant adenovirus Ad pl4ARF in cancer gene therapy. METHODS: The proliferation of different liver cancer cells was assessed by morphology and trypan blue assay. Cell apoptosis was confirmed by detecting phosphatidylserine (PS) externalization with Annexin V/PI double staining. The expression of related proteins was analyzed by Western bloting. Nude mouse model bearing subcutaneous transplanted BEL7402 tumor was established to study the therapeutic ability of Ad-pl4ARF. RESULTS: Ad-pl4ARF suppressed cell growth and proliferation, and promoted cell apoptosis of cancer cell lines with different genetic background. Ad-pl4ARF inhibited growth of liver cancer cells ( HepG2, BEL7402) in a dose-dependent manner. Ad-pl4ARF lead to overexpression of Bax and p21, the downstream regulating genes of p53. In the experimental therapy on nude mice bearing subcutaneous transplanted BEL7402 tumor, Ad-pl4ARF suppressed tumor growth significantly. CONCLUSION: pl4ARF is a short gene and with powerful function, which are consistent with the requirements for tumor suppressor genes used in gene therapy. It may play an important role in gene therapy against malignancies in the future. PMID- 17274366 TI - [Anti-metastatic effect of vascular endothelial growth factor receptor 2 extracellular domain gene-modified dendritic cell vaccination in murine model with experimental pulmonary metastasis]. AB - OBJECTIVE: To investigate the anti-metastatic effect of vascular endothelial growth factor receptor 2 extracellular domain gene-modified dendritic cell (DC sVEGFR-2) vaccination. METHODS: Dendritic cells (DC) were electroporated with pcDNA3. 1/sVEGFR-2 plasmid DNA. Expression of sVEGFR-2 was determined by ELISA. For immunization, C57BL/6 mice were intravenously injected three times with 1 x 10(5) cells per mouse of DC, pcDNA3. 1-transfected DC (DC-vector) , DC-sVEGFR-2, or 100 microl of PBS at 7-day intervals. At 10 days after the last immunization, the immunized mice were subjected to assessment of cytotoxic T lymphocyte ( CTL) response to VEGFR-2, alginate bead analysis of tumor cell-induced angiogenesis, and observation of the anti-metastatic effect in B16 melanoma metastasis model. CTL activity was determined by a standard 4-h 51Cr release assay against VEGFR-2 + vascular endothelial cell line H5V, 3LL cells stably transfected with pcDNA3. 1/sVEGFR-2 (3LL,-sVEGFR-2), and VEGFR-2- cell lines EL-4 and 3LL. Monoclonal antibodies GK1.5 anti-CD4 and 2.43 anti-CD8 were used to deplete in vivo CD4 + T cells and CD8' T cells, respectively. RESULTS: DC-sVEGFR-2 could effectively express sVEGFR-2, whereas DC-vector and DC could not. Immunization of mice with DC-sVEGFR-2 significantly induce CTL activity against VEGFR-2 + cell lines H5V and 3LL-sVEGFR-2, however, no significant CTL activity was observed when VEGFR-2- syngeneic cell lines EL-4 and 3LL. were used as target cells, implying this CTL activity was VEGFR-2 specific. Alginate bead analysis of in vivo neoangiogenesis showed that the inhibition reached 50% in mice vaccinated with DC-sVEGFR-2 compared with mice vaccinated with DC, DC-vector or PBS. Anti-metastatic experiment showed that profound reduction in pulmonary metastases was found in mice immunized with DC-sVEGFR-2, while mice immunized with PBS, DC, DC-vector developed extensive pulmonary metastases. The number of tumor nodules on lung surface decreased by 81.9% in mice immunized with DC-sVEGFR-2 when compared with mice immunized with DC-vector (49.7+/-12.7 vs. 9.0+/-3.2). In vivo T cell subset depletion experiments showed that the anti-metastatic effect of DC-sVEGFR-2 vaccination was abrogated in CD8 + T cell-depleted but not in CD4+ T cell depleted mice. CONCLUSION: Immunization of mice with DC-sVEGFR-2 could break self tolerance and induce a significant CTL response to VEGFR-2, leading to profound inhibition of tumor-cell induced angiogenesis and metastasis. This anti metastatic effect is mainly mediated by CD8+ T cells. PMID- 17274367 TI - [Effects of MT1-MMP on the in vitro invasiveness of breast cancer cells]. AB - OBJECTIVE: To investigate the effect of membrane type-1 matrix metalloproteinase (MTI-MMP) on the invasive potential of breast cancer cell and analyze its mechanisms. METHODS: After treatment of breast cancer MDA-MB-453 cell line with concanavalin A ( ConA, 20 microg/ml) for 24 h, MT1-MMP protein was detected in cancer cells by Western analysis and immunocytochemistry. MDA-MB-453 cells were cultured with exogenous latent proMMP-2 and MMP-2 activity was analyzed by gelatin zymography. The invasive potential of the tumor cells was measured with a membrane invasion culture system. Cancer cells of the cell line were divided into four groups: the control group treated by neither reagent, group ConA was only treated by ConA, group MMP-2 was treated only by MMP-2, and group ConA + MMP-2 was treated by both ConA and MMP-2. RESULTS The expression of MTI-MMP protein could be detected in groups ConA and ConA + MMP-2, but nothing was detected in control and group MMP-2. There was only 72 000 precursor form of MMP-2 in group MMP-2 and there were both 72 000 precursor form and 64 000 active enzyme form of MMP-2 in group ConA + MMP-2, but there was no forms of MMP-2 in the other two groups detected by gelatin zymography. The largest amount of cells penetrated through Matrigel was observed in group ConA + MMP-2 than in the other three groups. CONCLUSION: MTI-MMP can remarkably promote the invasive potential of breast cancer cells mainly through its ability of activating latent proMMP-2 to degrade PMID- 17274368 TI - [Suicidal cancer vaccine enhances anti-tumor immunotherapeutic effect and its safety in the treatment of ovarian cancer]. AB - OBJECTIVE: To study the anti-tumor immunotherapeutic effect induced by the suicidalcancer vaccine FC/TK, and to evaluate the safety of this vaccine. METHODS: The suicidal cancer vaccine, named FC/TK, was prepared by fusion of suicide gene (HSVI,-TK gene) -modified ovarian carcinoma NuTu-19 cells with rat bone marrow-derived dendritic cells (DCs). The morphology of FC/TK was evaluated by scanning electron microscopy. The stimulatory effect of FC/TK on T cells was determined by T cell proliferation assay. In immunotherapeutic studies in vivo, Fischer344 rats were injected subcutaneously with NuTu-19 cells, followed by treatment of FC/TK on days 7 and 14, compared to controls treated with irradiated FC/TK, FC or PBS, respectively. Tumor incidence and volume were measured in 90 days after challenge. To determine the killing effect of FC/TK in vivo, TUNEL assays were applied to detect apoptotic cell death in spleen of vaccinated rats with prodrug ganciclovir administration. RESULTS: FC/TK cells were of irregular shape with surface membrane processes. Compared to the control groups, FC/TK significantly promoted T cell proliferation (P <0.01). The rats vaccinated with FC/TK and FC significantly inhibited the tumor growth compared to rats vaccinated with irradiated FC/TK (P <0.05) or with PBS ( P <0.01). The immunotherapeutic effect induced by FC/TK was similar to that using FC. Fluorescence microscopy showed that fluorescein-stained FC/TK cells migrated into spleen also showed to be TUNEL-positive, suggesting that the FC/TK cells were killed by ganciclovir in vivo. CONCLUSION: Our data indicate that suicidal cancer vaccine is an effective and safe therapy for ovarian carcinoma and may serve as a broadly applicable approach for other cancer vaccines in the future. PMID- 17274370 TI - [Inhibitory effects of antisense MMP-9 oligodeoxynucleotides on invasiveness and adherence of ovarian cancer cells]. AB - OBJECTIVE: To observe the inhibitory effects of antisense MMP-9 oligodeoxynucleotides on invasiveness and adhesion ability in vitro of ovarian cancer cells, and to investigate the mechanisms of action. METHODS: MMP-9 antisense oligonucleotides were transfected by lipofectinmin into ovarian cancer cell line HO-8910PM cells expressing MMP-9 induced with fibronectin. RT-PCR, Western blot and gelatin zymography were used to detected MMP-9 expression of mRNA and protein and enzymatic activity. The ability of invasion and migration of ovarian cancer cells was assayed in Transwell cell culture chamber. Cell adhersion assay was carried out in a microculture well pre-coated with fibronectin. RESULTS: MMP-9 expressions of mRNA and protein were significantly decreased in the antisense-transfected cells. Comparing with the control group, the inhibition rate was 34. 8% and 42. 5% , respectively (P <0. 05). Its gelatin enzymatic activity was inhibited. Matrigel invasion assay and Transwell migration assay revealed markedly reduction in invasion and migration for the antisense group. The inhibition rates were 22. 4% and 24. 8% , respectively. The adhesion ability was also reduced. The inhibition rates were 49. 8% and 38. 3% at 60 min and 90 min, respectively. CONCLUSION: MMP-9 down-regulation can significantly inhibit the ability of invasion and attachment of ovarian cells in vitro. MMP-9 may play an important role in invasion and metastasis of ovarian cells and potentially be a molecular target of blocking invasion and metastasis of ovarian cancer. PMID- 17274369 TI - [Ad hTRP2 - mediated immunity against melanoma is enhanced by dendritic cells pulsed with peptide]. AB - OBJECTIVE: To investigate the enhanced effect of bone marrow-derived dendritic cells (DC) pulsed with SVYDFFVWL, a MHC class I peptide located in 180-188 amino acid residues of human melanoma-associated antigen tyrosinase- related protein 2 ( hTRP2) on the immunity against melanomas elicited by adenovirus encoding hTRP2 (Ad hTRP2). METHODS: The mice were intradermally immunized with Ad hTRP2, and three weeks later with Ad hTRP2 or DC/SVYDFFVWL once more. Analysis of CTL killing activity and IFN-gamma-producing CD8 + T cells in the total CD8 + T cells of spleen were made using in vivo CTL and intracellular staining of IFN-gamma, respectively. Additionally, the survival of mice was checked after the subcutaneous inoculation with mouse melanoma B16. F10 cells. RESULTS: The 6 h CTL killing and IFN-gamma producing CD8 +T cells in the total CD8 ' T cells of spleens were 68. 40%+/-5. 50% and 0. 67%+/-0.16% in Ad hTRP2 (priming)-Ad hTRP2 (boosting) group,28. 50%+/-6.40% and 0.22%+/-0.07% in DC/SVYDFFVWL (priming)-DC/ SVYDFFVWL (boosting) group,and 98. 90%+/-0.90% and 1.05%+/-0.21% in Ad hTRP2 (priming)-DC/ SVYDFFVWI, (boosting) group, respectively. In the tumor-bearing model, none of mice survived in DC/SVYDFFVWL (priming)-DC/SVYDFFVWL (boosting) group, and just only 40% of mice were tumor-free in Ad hTRP2 (priming) -Ad hTRP2 (boosting) group, whereas 100% of mice survived in Ad hTRP2 (priming) DC/SVYDFFVWL (boosting) group. CONCLUSION: Boosting with DC/ SVYDFFVWL can significantly enhance the immunity against melanomas elicited by priming with Ad hTRP2, indicating that first priming with Ad hTRP2 and then boosting with DC/SVYDFFVWL is a potentially effective regimen for overcoming the disadvantage that anti-tumor immune response can not be significantly increased by readministration of adenovirus. PMID- 17274371 TI - [X-chromosomal inactivation skewing in blood cells is associated with early development of lung]. AB - OBJECTIVE: To observe the relationship between skewed X-chromosomal inactivation (SXCI) and development of lung cancer in females. METHODS: DNA was isolated from peripheral blood cells from patients with primary lung cancer (n = 148) and control subjects (n =289). Exon 1 of androgen receptor ( AR) gene was amplified, with its products from different alleles resolved on denaturing polyacrylamide gels and visualized by silver staining. The corrected ratio (CR) between products from different AR alleles before and after Hpa II pretreatment was calculated. All statistical tests were two-sided. RESULTS: With CR> or = 10 adopted as the criterion, SXCI was found more frequently in the younger patients ( C50 years; 7. 9%) than in the controls of the same age group (1. 2% ; P = 0. 046). The SXCI frequency, however, were not significantly different between the old patients ( > 50 years; 4. 5% ) and the controls of the same age group (5. 4% ; P =0. 488). Whether taking CR> or =3 or CR> or =10 as the criteria, the average ages of the patients with SXCI were more than 10 years younger than those without SXCI (P < 0. 05). CONCLUSION: SXCI in blood cells is associated with early development of lung cancer in females. PMID- 17274372 TI - [A case-control study on the association between the genetic polymorphism of sulfotransferase 1A1, diet and susceptibility of colorectal cancer]. AB - OBJECTIVE: To investigate the relationship between sulfotransferase 1Al polymorphism, diet and colorectal cancer susceptibility. METHODS: A case-control study of 140 cancers and 343 health controls was conducted to investigate the role of sulfotransferase 1A1 polymorphism and meat consumption in colorectal carcinogenesis. Genotypes of sulfotransferase 1A1 polymorphism were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was no significant difference in allele frequency of SULT1A1 between the control and cancer patient populations. After adjustment for age, sex, smoking and history of diseases, red meat and well-done meat intake showed no significant association with colorectal cancer. Consumption of red meat more than 5 kg per year combined with SULT1Al slow sulfation (Arg/His and His/His) had a statistically significant association with the risk of rectal cancer ( OR = 3.78; 95% CI: 1.08 - 13. 20) compared to that consumed red meat less than 5 kg per year with fast sulfation (Arg/Arg). CONCLUSION: This study suggests that SULT1A1 slow sulfation combined with higher intake of red meat may be associated with an elevated risk of rectal cancer. PMID- 17274373 TI - [The usefulness of p16INK4a in cytological screening of cervical carcinoma]. AB - OBJECTIVE: To evaluate the value of p16INK4a immuncytochemical examination in cytological screening of cervical carcinoma and precancerous lesions. METHODS: p16JNK4a immuncytochemical detection was performed on 220 specimens remaining from liquid-based cytology, followed up by biopsy histology , and compared with the results of high-risk human papillomavirus ( HR - HPV ) DNA tests . Results In patients with cytological diagnosis of squamous cell carcinoma( SCC) , high-grade squamous intraepithelial lesion (HSIL) , low-grade squamous intraepithelial lesion (LSIL) , atypical squamous cells-cannot exclude HSIL (ASC-H) , and atypical squamous cells of undetermined significance (ASC-US) , the positive rates of p16INK4a were 100.0% (7/7), 92. 2% (107/116) , 24. 3% (17/70) , 100. 0% (14/14) and 36.4% (4/ 11) , respectively. In 111 of the 150 p6INK4a positive cases, we found 97 (87.4% ) cases which had biopsy diagnosises of > or =CIN2, but none in 18 of 70 p16INK4a negative cases was. The difference in the positive rates for p16INK4a between cervical intraepithelial neoplasia (CIN) 1 and > or =CIN2 lesions had statistical significance (P < 0. 01) , whereas for HR-HPV DNA test it was not. CONCLUSION: p16LNK4a is over-expressed in a HSIL, and it may be useful in cytological screening of high risk patients. PMID- 17274374 TI - [Expression of BCL-10 protein and the relationship with API2-MALT1 fusion gene in extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue]. AB - OBJECTIVE: To investigate the relationship of BCL-10 protein and API2-MALT1 fusion gene in MALT lymphoma. METHODS: Specimens from 86 cases of MALT lymphoma were studied by immunohistochemical staining for BCL-10. RT-PCR was used to detect the transcripts of API2-MALT1 fusion gene. RESULTS: In all 10 cases of Hashimoto thyroiditis only cytoplasmic BCL-10 expression in lymphoid cells was observed. In 86 MALT lymphoma cases, 42 cases (48. 8%) exhibited BCL-10 expression in both nucleus and cytoplasm. API2-MALT1 fusion gene was detected in 35 cases (40. 7%) of MALT lymphoma. BCL-10 nuclear expression was correlated with API2-MALT1 fusion gene transcript (r = 0. 374,P = 0. 000). CONCLUSION: BCL-10 nuclear expression is correlated with API2-MALT1 fusion gene expression in MALT lymphoma. PMID- 17274375 TI - [The diagnostic value of FDG coincidence imaging combined with serum tumor marker assays for pulmonary lesions]. AB - OBJECTIVE: To evaluate the performance of 18F-FDG three-head tomography with coincidence imaging and serum tumor marker assays in identifying lung lesions in 104 patients with abnormal findings on chest X-ray or computer tomography. METHODS: A prospective evaluation of 18F-FDG coincidence imaging and the measurement of 3 serum markers for lung cancer ( carcinoembryonic antigen, CYFRA21-1 and neuron specific enolase) were performed within one week in 104 inpatients with suspected lung malignancy. All images were analyzed visually. It was considered positive for malignancy if the 18F-FDG uptake was increased relative to that in the adjacent lung tissue, and was focal. The serum tumor marker test was considered positive for malignancy if the serum level of at least one marker was elevated. RESULTS: 66 patients were proven to have lung cancer by pathology, and 38 patients had benign lung diseases. The sensitivity, specificity, accuracy of 18F-FDG coincidence imaging and serum tumor markers in assessing lung cancers were 80. 0% , 77. 2% , 77. 9% and 56. 0% , 60. 9%, 64. 4% , respectively. 18F-FDG coincidence images in assessing lung lesions showed significantly higher sensitivity, specificity and accuracy than serum tumor markers. Four patients with lung cancer had negative findings on 18F-FDG coincidence images but showed positive serum markers. CONCLUSION: 18F-FDG coincidence imaging is a powerful tool for evaluating patients with lung lesions suggestive of malignancy. Although the determination of serum marker levels is less accurate than 18F-FDG coincidence imaging, the combination of a positive 18F FDG coincidence result and positive tumor markers may be helpful in improving the diagnosis of lung cancers. PMID- 17274376 TI - [Analysis of EGFR mutations in 176 cases of non-small cell lung cancer]. AB - OBJECTIVE: To analyze the incidence and profile of mutations in epidermal growth factor receptor (EGFR) in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: A total of 176 cases of NSCLC tissue was enrolled in this study, among which 123 normal lung samples were also included. The tissue DNA was extracted and the EGFR gene in exon 19 to 21 was subjected for PCR amplification and direct sequencing. RESULTS: The EGFR gene in exon 19-21 was of wild type in all normal lung tissues detected. Mutations were found in 57 cases of 176 lung cancer samples, with an incidence of 32. 4%. Mutations were mainly detected in the exon 19 (37/57 cases, 64. 9% ) and exon 21 (18/57 cases, 31. 6% ) , while that in the exon 20 was rare (2/57 cases, 3. 5% ). There were 7 types of EGFR mutation in the exon 19, resulting in the deletion of codon 746 to 753. A missense mutation was detected in exon 20, dealing with codon 789 to 793. The mutation in exon 21 belonged to the single missense substitution in codon 858. The EGFR mutations were more frequent in female patients than male ones, in adenocarcinoma and adenosquamous cell carcinoma versus cancer of other histologies. CONCLUSION: EGFR mutation is a tumor-specific somatic abnormality. Some one third of Chinese NSCLC tumors harbor EGFR mutations, especially in exons 19 and 21. These mutations are more frequently detected in female, adenocarcinoma and adenosquamous cell carcinoma. PMID- 17274377 TI - [Evaluation of serum pepsinogen I , II and osteopontin co-detection in gastric cancer screening]. AB - OBJECTIVE: To explore the value of combined assay of serum PG and OPN concentration for gastric cancer screening. METHODS: Pepsinogen I , II and osteopontin (OPN) concentrations in fasting serum were measured by ELISA in 570 subjects, including 144 gastric cancer, 60 dysplasia, 113 atrophic gastritis, 70 erosion or ulcer, 92 superficial gastritis and 91 healthy control. The cut off point for PG and OPN was determined using receiver operator characteristics curves (ROC). RESULTS: Using a serum PG I concentration < or =80 ng/ml, I: II ration < or =5.0 and OPN concentration > or =34 ng/ml or > or =30.4 ng/ml (based on ROC) for gastric cancer screening,the specificity, positive and negative predictive values were superior to that obtained by PG concentration only. Using a serumPGI concentration < or =50 ng/ml, I : II ration C 5. 0 and OPN concentration > or =35.2 ng/ml or > or =29. 2 ng/ml (based on ROC), the sensitivity, positive and negative predictive values were superior to that obtained by PG concentration only. Combining PG and OPN for gastric cancer screening, both sensitivity and specificity were more than 70% , while with OPN alone, only good specificity can be achieved. CONCLUSION: Combining different serum PG and OPN concentration for gastric cancer screening is superior to PG or OPN only. This may be used as a new method in gastric cancer mass screening. PMID- 17274378 TI - [Clinical significance of solitary lymph node metastasis in carcinoma of the ampulla of Vater]. AB - OBJECTIVE: To investigate the rule of distribution of solitary lymph node metastasis and its relation with clinico-pathologic factors in carcinoma of ampulla of Vater. METHODS: The data of 26 patients who were discovered to have solitary lymph node metastasis, from 152 patients with carcinoma of the ampulla of Vater who had received pancreatoduodenectomy were retrospectively reviewed. The related clinico-pathologic factors affecting it's metastasis were analyzed and compared with 105 such patients without any lymph node metastasis. RESULTS: Of these 152 patients with carcinoma of ampulla of Vater, 47(30. 9%) had lymph node metastasis and 26 had only solitary lymph node metastasis with a rate of solitary lymph node metastasis of 55. 3% (26/47). The majority of the solitary lymph node metastasis (84. 6% , 22/26) were located at the pancreaticoduodenal region, only 4 patients had skip metastasis. It was revealed by Chi-square test (chi(2) ) that solitary lymph node metastasis was correlated with the tumor size (P = 0. 007) , histological differentiation(P = 0. 003) , T stage(P = 0. 000) and pancreatic infiltration (P =0. 009). CONCLUSION: The majority of solitary lymph node metastasis are located at the pancreaticoduodenal region. Sentinel lymph node assessment may be helpful to determine the extent of lymph node dissection for carcinoma of the ampulla of Vater. PMID- 17274379 TI - [Value of multi-slice helical CT in the diagnosis and differential diagnosis of thyroid lesions]. AB - OBJECTIVE: To investigate the value of multi-slice helical CT in the differentiation of benign from malignant thyroid lesions. METHODS: The multi slice helical CT images of 72 patients with 82 thyroid lesions were prospectively studied. The CT features including the margin, density of the lesion and cervical lymph node enlargement were evaluated double-blindly. All the image findings were compared with the pathological results, and analyzed statistically using the Chi square test. RESULTS: Of 42 benign lesions, 38 (90.5 % ) showed well-defined margin, 13 (30. 9% ) contained low density nodular areas, 3 (7. 1% ) showed granular calcifications, and 2 (4. 8% ) had cervical lymph node enlargement. Of 40 thyroid carcinomas, 37 lesions(92.5% ) had irregular border, no lesion contained low density nodular areas, 14 (35. 0%) showed granular calcifications, and 31 (77. 5% ) had enlarged cervical lymph nodes. Nineteen lesions (55. 9% ) from 34 thyroid carcinoma patients who had undergone contrast enhanced CT scan showed complex density, while only 2(6. 3% ) of 32 benign lesions showed such findings on contrast enhancement. There were statistically significant differences between benign and malignant lesion in margin, low density nodular area, granular calcification, cervical lymph node enlargement and complex density( P <0.01). CONCLUSION: The findings of well-defined margin and low density nodular area in CT image may suggest benign thyroid lesions, whereas the presence of irregular border, granular calcifications and cervical lymph node enlargement as well as complex density may indicate thyroid malignancy. PMID- 17274380 TI - [Value of computed tomography in the staging and predicting resectability of primary advanced ovarian carcinoma]. AB - OBJECTIVE: To assess the value of computed tomography( CT) in the staging and predicting respectability of primary advanced ovarian carcinoma. METHODS: The data of preoperative abdomen and pelvis CT scan in 64 women with Stage II or IV ovarian carcinoma were collected from tumor registry database. All CT scans were analyzed retrospectively without knowledge of the operative findings, and the stage as based on CT was compared with the surgical and pathological findings. Residual lesion of < or = 2 cm in maximal diameter was considered as an optimal surgical result. Twenty-senven of these 64 patients (42.2%) underwent optimal cytoreduction surgery for residual disease C2 cm in diameter. Based on the ability of each parameter in predicting cytoreductive surgery outcome, 11 radiographic features were selected for the final model. Each predictive parameter was assigned a numeric value (1 to 7). Sensitivity, specificity, positive predictive value( PPV) , negative predictive value( NPV),and accuracy were calculated for each predictive parameter. Receiver operating characteristic( ROC) curve was used to assess the ability of the model to predict surgical outcome. The correlation between CT stage and surgical-pathologic stage was analyzed by Chi-square test and Spearman's rho analysis. RESULTS: The overall accuracy of CT staging for advanced ovarian carcinoma was 87. 5% ; 86. 5% and 91.7% for stage III and IV patients respectively. The correlation between CT stage and surgicopathologic stage was found to be comformable. In the final predictive index model, when a predictive index scoreed > or = 2, the overall accuracy, sensitivity and specificity was 70. 3% , 67.6% and 74. 1% for identifying patients for suboptimal surgery. The PPV and the NPV was 78. 1% and 62. 5% , respectively. The ROC curve was generated with an area under the curve = 0. 792+/-0. 055 using the predictive index scores. CONCLUSION: CT has a high accuracy in staging and a moderate ability to predict resectability for advanced ovarian carcinoma. Therefore, the predictive index model may be useful in the management of ovarian carcinoma patients. PMID- 17274381 TI - [Multicenter randomized control trial on safety of domestic idarubicin for acute leukemia]. AB - OBJECTIVE: To evaluate the safety of domestically produced idarubicin in the treatment of acute leukemia by a multicenter randomized control trial. METHODS: This trial was carried out in the hemotologica department of five hospitals throughout China, with hospitalized patients who suffered from acute myelogenous leukemia ( AML except M3 type) , acute lymphocytic leukemia ( ALL) , chronic myelogenous leukemia-blast (CML-blast) , totally 155 patients. Those with severely cardial, hepatic or renal disfunction or those who had ever treated with > or = 200 mg/m(2) idarubicin were excluded from the trial. All patients signed the letter of consent as required by the Ethics Committee of our government. In this study, 155 leukemia patients were randomly grouped into: 1. test group treated using domestic idarubicin, 2. control group using imported idarubicin. The acute myelogenous leukemia regimen included idarubicin 8 mg/m(2), dl -3 plus cytosine arabinoside 100 mg/m(2), dl - 7 for 1-2 cycles. The regimen for acute lymphocytic leukemia was idarubicin 8 mg/m2, dl - 3; vincristine 2 mg/mr, dl; cyclophosphamide 750 mg/m2, dl ; plus prednisone 60 mg/m(2),dl - 14 for 1-2 cycles. RESULTS: Clinical response rate of the tested group treated with domestic idarubicin and control group treated with imported idarubicin was 78. 1% (50/64) vs. 76.9% (50/65) without any statistically significant difference between the two groups(P >0. 05). Grade Ill - IV hematological toxicity rate of the domestic idarubicin group and imported idarubicin group was 74. 0% vs. 73. 1% , respectively (P = 0. 73). Drug-related death was observed in 3 of 77 patients in the domestic idarubicin group (3.9%) due to cerebral hemorrage or septic infection. The incidence of non-hematological toxicities in domestic idarubicin group and imported idarubicin group was 84. 4% vs. 79. 5% for nausea or vomiting, 70. 1% vs. 71. 8% for infection, 42. 9% vs. 41. 0% for mucositis, 33. 8% vs. 33. 3% for alopecia, 28.6% vs. 28. 2% for serum glutamicoxalacetic transaminase abnormalitis, 16. 9% vs. 10. 3% for cardiac toxicity, all without statistically significant differences between these two groups (P > 0. 05). Discontinuation of treatment due to non-hematological toxicity was not neccessary. CONCLUSION: Domestic idarubicin is comparable to imported counterpart in efficiency and safety for the treatment of acute leukemia. The most severe side effects of domestic idarubicin is hematological toxicity, which should be closely observed and treated in time, while its non-hematological toxicity is tolerable. PMID- 17274382 TI - [Results of multimodality therapy for unresectable primary liver cancer]. AB - OBJECTIVE: To investigate the therapeutic measures for unresectable primary liver cancer (PLC). METHODS: The date of 312 unresectable primary liver cancer patients treated from January 1991 to March 2003 were retrospectively analyzed. RESULTS: Of these 312 patients, 73 were treated by cryosurgery-based combined modality therapy, 239 were treated by a TACE-oriented combined modality therapy. 289 patients except 23 were followed for a period of 2 to 156 months. The overall 1 ,3- and 5-year survival rate in this series was 74. 0% , 34. 0% and 16. 7% , respectively. The 1-,3-and 5-year survival rate in the cryosurgery group was 64. 4% , 38. 4% and 27. 4% , respectively. The 1-, 3- and 5-year survival rate in the TACE group was 75. 1% , 29. 0% and 10. 0%, respectively. CONCLUSION: Treatment for the unresectable primary liver cancer should be individualized and combined with suitable therapeutic modalities. PMID- 17274384 TI - [Application and recent research progress of irinotecan in treatment of advanced colorectal cancer]. PMID- 17274385 TI - [Development of Satisfaction and Burden scales for community activities of health promotion volunteers]. AB - PURPOSE: Health promotion volunteers (HPVs) who are members of community health organizations are being fostered by local governments to work in local communities in Japan. The purpose of this study was to develop Satisfaction and Burden Scales for HPVs in their community activities. METHODS: The subjects were 604 HPVs in two cities in a prefecture. Based on the findings of preliminary interviews, ten items for the Satisfaction Scale and fourteen items for the Burden Scale were prepared, and their content validities were confirmed. A mail in self-check questionnaire survey was conducted in September 2005. RESULTS: A total of 433 questionnaires were analyzed (valid response rate: 71.7%). Two factors and nine items for the Satisfaction Scale and three factors and fourteen items for the Burden Scale were obtained based on factor analysis. Convergent validities of both scales and discriminant validity of the Burden Scale were supported by the results of the multitrait-multimethod matrix for Satisfaction and Burden Scales, and one item each for general satisfaction and general burden regarding their activities. The reliabilities of both scales were confirmed with reference to the Cronbach's alpha coefficient. Moreover, all item-total correlations were moderately or strongly positive. CONCLUSION: This study provided support for the reliability and the validity of Satisfaction and Burden Scales for HPVs in their community activities. The applicability of both scales is suggested. PMID- 17274383 TI - [Malignant tumor with false negative 18F-FDG PET image]. AB - OBJECTIVE: To investigate the FDG uptake characteristics, the factors affecting 18F-FDG uptake and the extra CT diagnostic value of 18F-FDG PET/CT scan in the malignant tumor with false negative 18F-FDG PET image. METHODS: The data of PET/CT image in 17 patients with various kinds of cancers were reviewed and analyzed by visual observation and semi-quantity analysis ( SUV). The results were compared with the CT and histopathological diagnosis, respectively. RESULTS: Of 6 well-differentiated HCC patients confirmed by histopathological diagnosis, one had two lesions in the right lobe of the liver. One of these two lesions showed low FDG uptake on 18F-FDG PET scan and low density on CT scan. The other one was not shown on either 18F-FDG PET or plain CT scan. But on enhanced CT scan, these two lesions were found to be inhomogeneous with high density at arterial phase. The false negative 18F-FDG PET images of one gastric signet ring cell carcinoma in the gastric fundus with right adnexa metastasis, 3 renal cell carcinoma, one greater omentum and peritoneal metastatic adenocarcinoma and one well-differentiated prostate cancer were caused by normal physical uptake in the digestive tract or FDG retention in the urinary system due to normal excretion. The size of three metastases was smaller than or equal to 1 cm in diameter, however, two primary lesions of these metastases showed high FDG uptake and only one was negative on either 18F-FDG PET or CT scan. In this series, 68.8% of the primary tumors and 66.7% of metastases were found to show abnormal density on CT scan, and 31. 2% of the primary tumors and 33. 3% of metastases were not detectable on either PET or CT images. CONCLUSION: False negative 18F-FDG PET in malignant tumor may be correlated with the pathologic type, differentiation degree and the lesion size. Combining CT information with PET or paying attention to the scan methods during 8 F-FDG PET examination may reduce the rate of false negative 18F-FDG PET diagnosis in various kinds of malignant tumors. PMID- 17274386 TI - [Mothers' perceptions and vaccination coverage]. PMID- 17274387 TI - [Volunteers' recognition of problems in meal distribution service and their expectation for information concerning health and welfare in less-favoured areas]. AB - OBJECTIVE: This study aimed to clarify problems perceived by volunteers of a meal distribution service (MDS) in Less-Favoured Areas and the content of information expected to be provided by the administration and social welfare council. METHODS: We chose three municipalities (A, B, and C) with a population of less than 4,000 and an elderly population rate of 25% or higher. Volunteers involved in MDS in the municipalities were 28, 11, and 22 people in A, B, and C, respectively. We interviewed each group after explaining our purpose in writing, and made word-for-word records. Survey items were as follows; what you try and aim to do, what is your burden and pleasure, what are your problems and the solutions, and what are your demands for future activity in the MDS. The study period was from March to November, 2003. RESULTS: The information that the volunteers expected the administration and social welfare council to provide encompassed 3 categories, each of which contained 2 subcategories. They expected (information to allow elderly people to use the service on their own initiative> and as [information to improve understanding of the users and residents about the aims and contents of the MDS], and as [information to ensure the quality and quantity of volunteers], and and as [information to improve the relationships between the volunteers and users]. CONCLUSIONS: The volunteers expected education to improve the understanding of the residents so that elderly people can use the MDS on their own initiative, recruiting of motivated volunteers to ensure continuation of the service, and support for the smooth execution of the service and a system for such support. These were perceived by the subjects as problems to be solved for effective implementation of the service, and are considered to represent the meaning and state of the MDS that the volunteers wanted to share with the administration, social welfare council, and residents. The information that should be shared among the administration, social welfare council, residents, and volunteers can be clarified by evaluation of the expectations of the volunteers which must be met to promote their cooperation to support the service. PMID- 17274388 TI - [Living areas considered by healthy elderly people living in the suburbs of a metropolitan area]. AB - PURPOSE: The purpose of this study was to identify living areas perceived by healthy elderly people living in A, a Metropolitan city. The study also focused on the influences of age, gender, and family structures, residence period, the level of instrumental activities of daily living (the IADL), and frequency of weekly outing of the elderly upon their perceptions. METHODS: The inclusion criteria for the study subjects were: (1) elderly people aged 65 and over living in A city, and (2) not receiving Long-Term Insurance services. The survey period was between January and February in 2005. Self-administered questionnaires were sent to 4,000 randomly selected elderly people by mail and 3,070 (77.0%) questionnaires were returned. 2,692 (67.3%) of these could be analyzed. RESULTS: The majority of respondents perceived the entire area of A city and the local center's area as living areas. Junior high school districts and primary school districts were stated by less than 3% of all respondents as within their living areas. Regarding gender, men were more likely to respond that the local center's area was their living area, whereas women considered that the whole area of A city was included. However, there was no statistically significant difference. In terms of age, respondents aged under 79 included the whole area of A city, whereas those aged 80 and under stated that their areas of self-governing body/neighborhood association were their living areas, indicating reduction in living areas with aging. Regarding the family structure of the respondents, the most frequent answer was the entire K city in subjects in all types of households except those consisting of the subject and parents, who most frequently regarded local center's as the living area. Respondents who were living 10 years and over in K city perceived that the whole area of the city was included, but respondents residing for under 10 years perceived the local center's area to be their living area. With regard to the level of the IADL, independent elderly responded the entire city, whereas dependent elderly responded the local center's area. Moreover, the living areas of respondents became smaller with decrease in the frequency of weekly outing. CONCLUSION: The living areas perceived by elderly people differ depending on their attributes, including age and gender, IADL, frequency of weekly outing, and the period of residence. In order to provide support to facilitate the elderly staying at home, we need to consider their backgrounds and thoughts. Further investigation is necessary to identify the influences of the characteristics and environments of communities upon the elderly perception of living areas. PMID- 17274389 TI - [Posttraumatic stress disorder in different types of stressful influences]. AB - Two types of stressful influences--the participation in combat actions and the liquidation of the Chernobyl accident consequences have been compared. Thirty combatants and 33 liquidators were followed up 5-6 and 15-17 years after the extreme situation. Clinical presentations have been analyzed using main criteria of posttraumatic stress disorder (PTSD), i.e. immersion in the experiences, avoidance, hyperactivity and social functioning. Common and peculiar presentations depending on the stress character have been found. Patients received coaxil in dosage 37.5 mg daily during 4 weeks. In both groups, the drug exerted the highest effect on symptoms of immersion and hyperactivity that improved the social adaptation. Avoidance symptoms were more resistant. It has been concluded that coaxil is an effective medication for the treatment of different PTSD types. PMID- 17274390 TI - [Cognitive disturbances in multiple sclerosis]. AB - Results of the study of cognitive functions in children with multiple sclerosis (MS), including literature data on cognitive disturbances in this disease, are presented. Fourteen patients, aged from 8 to 17 years, with definite MS have been studied. A neuropsychological study revealed impulsivity in the performance of tasks without the sufficient orientation on the test instruction; difficulties in the visual perception in conditions of different complexity and difficulties of the simultaneous synthesis; elements of the left-side ignoring, difficulties in understanding, the usage of logical grammatical construction, activity programming and the rhythm perception. These peculiarities are interpreted in the context of A.R. Luria conceptions on the marked impairment of the functional activity of the right hemisphere, reduction of an operational constituent of mental processes related to the activity of the second functional block in the brain (parietal, occipital and temporal areas); decrease of regulatory aspects of the activity related to the activity of the third structural-functional block, which included the convexital frontal cortex with all the cortical and subcortical connections; reduction of the activating provision of mental processes related to the work of the first structural-functional block (deep, subcortical brain structures and their connections). It is emphasized that cognitive disturbances in children may appear on the earlier stages of MS. PMID- 17274391 TI - [Mental disorders in children after the sexual abuse]. AB - Consequences of intrafamily noncontact abuse (40 children aged from 3 to 13 years) and out-of-family contact abuse (15 children aged from 7 to 15 years) have been studied. The intrafamily abuse was long-term and demanded from a child the immersion into situation of "secrecy". The out-of-family abuse had a character of the extreme influence upon a victim. Independently of the abuse character, border line mental disorders were found in all children. A character of these disorders was determined by the specifics of psychogenic factor, its duration and child's age. A decreased mood, different levels of autism and disturbances of cognitive function were common features of border-line disorders. In cases of intrafamily abuse, uncontrolled drives, sexual character of games and fantasies, elements of depersonalization and age-specific transformation of affective disorders from depressiveness to dysphoric aggressive reactions were observed. In the out-of family contact abuse, especially in teenagers, the main appearances approached to posttraumatic stress syndrome. In all cases, there was a trend to stronger differentiation of affective disorders, intensification of drives and formation of characteristic pathologic changes as children get older. PMID- 17274392 TI - [Systemic thrombolysis in ischemic stroke]. AB - Intravenous recombinant tissue plasminogen activator (rt-PA) is an approved and effective treatment for acute ischemic stroke within 3 hours of symptoms onset. The results of the first-ever implementation of the thrombolysis in the Russian Federation are presented. Fourteen stroke patients received rt-PA in dose of 0.9 mg/kg (10% as a bolus during 1 minute followed by infusion), the mean "door-to needle" time was 50 +/- 23.6 min. The thrombolysis resulted in the clinical improvement by the end of the first day after stroke onset in 9 (64.2%) patients, with a dramatic regress of neurological deficit (the decrease of the NIHSS scores = 4) in 3 (21.4%) of them. Hemorrhagic transformation was observed in 6 (42.8%) patients, however in 5 cases it was asymptomatic and was found only in the repeated CT study to the end of the first day. Three months after stroke onset, 7 (50%) patients scored 0-1 on the modified Rankin scale, 1 patient had 4 scores and 1 patient died. Thus the thrombolysis can change the stroke management and significantly improves the outcome. PMID- 17274393 TI - [High efficacy of selective intra arterial thrombolysis in ischemic stroke patients with large-vessel occlusion]. AB - Thrombolysis is the most effective treatment of acute ischemic stroke that increases the proportion of patients with good clinical outcome. Selective intra arterial thrombolysis (IAT) can be used in a wider therapeutic window (up to 6-8 hours) under the angiographic control with tailoring of fibrinolytic dose. The results of IAT by a recombinant plasminogen activator in 2 patients are presented. Patient 1, male, 55 years old, with M1 cerebral middle artery (CMA) occlusion and with NIHSS score 13 on admission was treated by IAT after 7 hours of stroke onset. Recanalization was observed 40 minutes after IAT started. The NIHSS score was 8 after IAT. Patient 2, female, 64 y.o., with NIHSS score 20 on admission and C7 internal carotid artery and M1 CMA occlusion was treated by IAT. Recanalization was observed 60 minute after the beginning of IAT, with NIHSS score being decreased to 14. These clinical cases demonstrate the high efficacy of intra arterial thrombolysis in ischemic stroke patients. PMID- 17274394 TI - [Tanakan (EGb 761) in the therapy of mild cognitive impairment]. AB - Mild Cognitive Impairment (MCI) means cognitive deterioration not yet causing disability or dementia. Aged patients with MCI constitute a group of high risk for Alzheimer disease and other types of dementia. Currently, there is no generally adopted approach to MCI management but medications with neuroprotective properties are presumed to be the most perspective. Presented are the results of a multicentral open-label clinical trial of vascular and neuroprotective drug tanakan (EGb 761). The study has shown the decrease of cognitive impairment, which was both clinically and statistically significant, in patients at early stages of vascular and neurodegenerative pathological process. Probable efficacy of long-term tanakan treatment in prevention of dementia is discussed. PMID- 17274395 TI - [Mathematical analysis of EEG in consciousness recovery after traumatic brain injuries]. AB - The clinical and EEG study of 20 patients with post-comatose consciousness disturbances caused by severe traumatic brain injuries (9 patients with autonomic state and 11 with Korsakoff syndrome), applying a statistical method of analysis of EEG spectrum and coherent connections developed by the authors, has revealed pathological features of the EEG interhemispheric connections. Patients with consciousness disturbances exhibited (1) total functional disconnections of hemispheres which was characteristic of the autonomic state and (2) disconnection in frontal areas of the brain in patients with Korsakoff syndrome as compared to the normal spatial distribution of coherence observed in 40 healthy people. Consciousness recovery has been accompanied by interhemispheric connections normalization, at first in the posterior regions of the hemispheres and then in the anterior ones as well as by transforming of coherence profile in the shape of "envelope" being most typical for the normal pattern of coherence distributation. PMID- 17274396 TI - [An electrophysiological study of the rehabilitation of cognitive functions during the treatment of patients with panic disorders]. AB - To investigate psychophysiological features of panic disorder (PD) before and after treatment with citalopram, P300 auditory event-related potentials (ERPs) were recorded in 31 patients who met the DSM-IV criteria of PD and 24 age- and sex-matched normal controls. The ERPs were recorded during a standard two-tone discrimination task (oddball task). The treatment was conducted as a monotherapy during 6 weeks, with citalopram dosage of 20 mg/day. Compared to controls, patients differed significantly by the reduced P300 amplitude and the alteration of its habituation. These patients also demonstrated more pronounced anxiety, depression, autonomic dysfunction, alexithymia and attention insufficiency. High efficacy of the medication was detected in 80,7% of patients. The data obtained demonstrate disturbances of cognitive function in PD patients as well as qualitative psychoneurophysiologic differences of patients before and after the treatment which were most striking for the wave amplitude and for the alteration of its habituation. It is concluded that P300 evaluation may be used as a diagnostic tool and should be taken into account in the choice of effective therapy for PD patients. PMID- 17274399 TI - [Pathophysiological mechanisms realizing in the brain during its focal lesion (cerebral supratentorial stroke)]. PMID- 17274397 TI - [Dysregulation of cytokine production by mononuclear cells of peripheral blood in persistent infection with a virus of tick-borne encephalitis]. AB - Tick-borne encephalitis is accompanied by dysregulation of cytokine production of mononuclear leucocytes of peripheral blood. The changes of production of IFN-r by mononuclear leucocytes of peripheral blood positively correlated with a degree of activity of pathological process and intensity of clinical symptoms of neuroninfection. On the contrary, secretion of IL-12 mononuclears directly correlated with virus persistence in the organism and does not depend on clinical presentation of the disease. PMID- 17274398 TI - [Psychotherapy in correction of psychosomatic status and in women with pathological course of menopause]. PMID- 17274401 TI - [The formation of the blood vessels of the human embryonic brain in conditions of prenatal alcohol exposure]. PMID- 17274400 TI - [The use of sulbuthiamine (enerion) in the combined therapy of patients with symptomatic focal epilepsy]. PMID- 17274402 TI - [The current approaches to diagnostics and therapy of fluctuations in Parkinson's disease]. PMID- 17274403 TI - [Duration and principles of the prescription of neuroleptics in maintain therapy]. PMID- 17274404 TI - [Fees for and rights of prescription drugs for patients]. PMID- 17274405 TI - [Reeducation and readaptation, a conference totally devoted to seduction]. PMID- 17274406 TI - [Seroprevalence of hepatitis C is highly elevated by the use of drugs]. PMID- 17274407 TI - [Liberal nurses at the crossroads]. PMID- 17274408 TI - [Badly controlled severe persistent asthma: an additional new treatment]. PMID- 17274409 TI - [Adaptation to a digestive stoma. Prospective study to evaluate a two-piece system joined by a supple adhesive]. PMID- 17274410 TI - [50 years of nursing]. PMID- 17274411 TI - [1956, a year of crises and discovery]. PMID- 17274412 TI - [50 years of history and discovery]. PMID- 17274413 TI - [The field of writing, fifty years of professional literature]. PMID- 17274414 TI - [Nursing, a "trans-mission"]]. PMID- 17274415 TI - [Combination of nursing and medicine from 1900 to our day]. PMID- 17274416 TI - [1956-2006, fifty years of the nursing profession]. PMID- 17274417 TI - [The image and the reality of a nurse]. PMID- 17274418 TI - [50 years of change as a liberal exercise]. PMID- 17274419 TI - [Desperate wounds and interesting wounds]. PMID- 17274420 TI - [The patient in pain]. PMID- 17274421 TI - [Therapeutic function of the stoma nurse, from its creation to...today]. PMID- 17274422 TI - [Being a psychiatric nurse these days]. PMID- 17274423 TI - [Evolution of the role of nurses in diabetology, a curative and educational approach]. PMID- 17274424 TI - [Carrying an Accu-Chek kit: the role of the nurse in education in diabetology]. PMID- 17274425 TI - [Nursing in resuscitation, an expert technique for the clinic to recognize]. PMID- 17274426 TI - [Professional chronology of the nurse in cardiology]. PMID- 17274427 TI - [Having been, being, and becoming a nurse in vascular pathology]. PMID- 17274428 TI - [Function of the nurse in re-education and re-adaptation]. PMID- 17274429 TI - [Anesthesia nurses, a profession of its own]. PMID- 17274430 TI - [Operating room nursing, the care at the heart of the technology]. PMID- 17274431 TI - [Pediatric nurses at the heart of a diverse medium]. PMID- 17274432 TI - [The nurse in nephrology, new technology and every-day care]. PMID- 17274433 TI - [Role of the nurse in occupational nursing]. PMID- 17274434 TI - [Nursing perspective and nursing diagnosis]. PMID- 17274435 TI - [Clinical nursing, a passion]. PMID- 17274436 TI - [Community health nursing and its real functions]. PMID- 17274437 TI - [Developing a framework for health, or not]. PMID- 17274438 TI - ["Why not to develop a health framework..."]. PMID- 17274439 TI - [Nursing staff in private hospitals, chronicle of an advanced metamorphosis]. PMID- 17274440 TI - [Nurses and research]. PMID- 17274441 TI - [Initial formation and practice of nursing, a half-century of evolution]. PMID- 17274442 TI - [Scarcity of nursing personnel and valuation of "nursing resource"]. PMID- 17274443 TI - [Future of nurses in thinking of the present]. PMID- 17274444 TI - [Nursing profession in 2006, evolution or mutation?]. PMID- 17274445 TI - [What is the future of the nursing profession?]. PMID- 17274446 TI - [Nursing system and a caring deity, a tail of humanism]. PMID- 17274447 TI - Structure-property relationships of DEAEM-containing bone cements: effect of the substitution of a methylene group by an aromatic ring. AB - New aromatic methacrylates were prepared by substitution of a methylene group from diethylaminoethyl methacrylate (DEAEM) by an aromatic ring at two different positions. Diethylamino benzyl methacrylate (DEABM) and N-methacryloyloxyethyl)-N ethyl-m-toluidine (MEET) were polymerized and incorporated as co-monomers in bone cement formulations. Cements were evaluated in terms of curing and mechanical properties in addition to changes in their glass transition temperature by DSC and surface properties by contact angle measurements. The immediate effect of the presence of an aromatic ring within the amino methacrylate was that it modified the bone cements' physical appearance, as colored products were obtained. It was also observed that peak temperature increased and setting time decreased by the use of DEABM and MEET instead of DEAEM. Simultaneously, both tensile and compressive strength of bone cements were improved; this effect was related to a higher glass transition temperature. In addition, surface properties of cements were modified by the incorporation of the aromatic ring, being more hydrophilic at low molar fractions and more hydrophobic at high molar fractions. Based on these studies, it is concluded that the position of the aromatic ring within the amino methacrylate modified not only the cement's appearance, but also the setting and mechanical properties. PMID- 17274448 TI - Controlled immobilization of chondroitin sulfate in polyacrylic acid networks. AB - Novel semi-interpenetrating polymer networks (semi-IPNs) of chondroitin sulfate (ChS) and acrylic acid (AA) were prepared with the aim of obtaining a hydrogel for use as a colon-specific drug carrier. By controlling the concentrations of cross-linking agent, diethylene glycol dimethacrylate (DEGDA), as well as the reaction solvent, high swelling percentages were obtained (approx. 1600%). However, the highest sol percent obtained for these hydrogels was approx. 70%, and most of the chondroitin sulfate remained soluble and could be extracted. Therefore, an alternative approach was adopted: methacrylate-grafted ChS (ChSMA) was synthesized and then co-polymerized with acrylic acid (AA) at a molar ratio of 1:5 with various concentrations of AA. The sol content of these ChSMA-AA hydrogels was reduced to approx. 20%, and the cross-linking densities were almost 100-fold higher than those of the semi-IPNs. FT-IR spectra showed that the H bonding interactions between ChS and PAA and the spectra of the semi-IPNs were similar to that of PAA itself after sol extraction. In contrast, the FT-IR spectra of ChSMA-AA remained intact after sol extraction. Ketoprofen was used as a model drug to test the sustained release behavior of these hydrogels. PMID- 17274449 TI - Synthesis and characterization of a pH-sensitive hydrogel made of pyruvic-acid modified chitosan. AB - Pyruvic-acid-type chitosan (PA-CS) was prepared by the reaction of an amine group on chitosan with a carbonyl group on pyruvic acid. Then, a novel hydrogel film was obtained via cross-linking of poly(ethylene glycol) diglycidyl ether (PEGDE) with PA-CS. 1H-NMR and FT-IR spectrometry were applied for the verification of the CS and PA-CS structure. The degree of swelling was studied by changing the molar ratio of PEGDE and PA-CS. Moreover, the swelling ratio of cross-linked membrane in different pH buffer solutions was measured. The result showed that the swelling of hydrogel exhibited obvious pH-sensitivity. The swelling ratio was higher at pH 1-4 and pH 7-12, but lower at pH 5-6. PMID- 17274450 TI - Hybrid braided 3-D scaffold for bioartificial liver assist devices. AB - Three-dimensional ex vivo hepatocyte culture is a tissue-engineering approach to improve the treatment of liver disease. The extracorporeal bioartificial liver (BAL) assists devices that are used in patients until they either recover or receive a liver transplant. The 3-D scaffold plays a key role in the design of bioreactor that is the most important component of the BAL. Presently available 3 D scaffolds used in BAL have shown good performance. However, existing scaffolds are considered to be less than ideal in terms of high-density cultures of hepatocytes maintaining long-term metabolic functions. This study aims to develop a 3-D hybrid scaffold for a BAL support system that would facilitate high-density hepatocyte anchorage with long-term metabolic functions. The scaffolds were fabricated by interlacing polyethylene terephthalate (PET) fibers onto the polysulfone hollow fibers utilizing a modern microbraiding technique. Scaffolds with various pore sizes and porosities were developed by varying braiding angle which was controlled by the gear ratio of the microbraiding machine. The morphological characteristics (pore size and porosity) of the scaffolds were found to be regulated by the gear ratio. Smaller braiding angle yields larger pore and higher porosity. On the other hand, a larger braiding angle causes smaller pore and lower porosity. In hepatocyte culture it was investigated how the morphological characteristics (pore size and porosity) of scaffolds influenced the cell anchorage and metabolic functions. Scaffolds with larger pores and higher porosity resulted in more cell anchorage and higher cellular functions, like albumin and urea secretion, compared to that of smaller pores and lower porosity. PMID- 17274451 TI - Wear of '100 Mrad' cross-linked polyethylene: effects of packaging after 30 years real-time shelf-aging. AB - Studies have shown that gamma-irradiation of polyethylene (PE) generally results in degradation by surface oxidation. However, from 1970 to 1978 Oonishi et al. used ultra-high-molecular-weight polyethylene (UHMWPE) cross-linked and sterilized by 100 Mrad of gamma-irradiation in air (100 Mrad PE) for total hip prostheses, and obtained excellent clinical results extending for 30 years. In the present study, we used a hip joint simulator to investigate the wear characteristics of 100 Mrad PE cups which had been shelf-aged for an extremely long period (30 years). The PE cups, aged in an air-containing triple polyethylene package for 30 years (packaged 100 Mrad PE), showed low wear with 3.4 mg of weight loss, even after 5 x 10(6) cycles. In contrast, non-packaged 100 Mrad PE showed considerable wear: 47.0 mg at run-in ((0-0.25) x 10(6) cycles) and 114.1 mg at the end of 5 x 10(6) cycles. The substantially, lower wear even in the presence of an oxidized surface layer for the packaged 100 Mrad PE, was comparable to the low wear seen on retrieved 100 Mrad PE after 30 years of clinical use. The long-term shelf-storage conditions, which affect the surface oxidative degradation of PE, are assumed to be the key factor in the wear resistance of gamma-irradiated UHMWPE. PMID- 17274452 TI - Preparation of novel silica-coated alginate gel beads for efficient encapsulation of yeast alcohol dehydrogenase. AB - Biomimetic formation has undoubtedly inspired the preparation of novel organic inorganic hybrid composites. In this study, silica-coated alginate gel beads were prepared by coating the surface of alginate gel beads with silica film derived from tetramethoxysilane (TMOS). The composition and structure of the silica film were characterized by FT-IR and SEM equipped with EDX. The swelling behavior of silica-coated alginate gel beads was studied to be more stable against swelling than that of alginate gel beads. The results showed that silica-coated alginate gel beads exhibited appropriate diffusion property. The effective diffusion coefficient (D(e)) of NADH in silica-coated alginate beads was 1.76 x 10(-10) m2/s, while the effective diffusion coefficient in alginate beads was 1.84 x 10( 10) m2/s. The model enzyme yeast alcohol dehydrogenase (YADH) was encapsulated in silica-coated alginate and pure alginate beads, respectively. Enzyme leakage of YADH in alginate gel beads was determined to be 32%, while the enzyme leakage in silica-coated alginate gel beads was as low as 11%. Furthermore, the relative activity of YADH in alginate gel beads decreased almost to zero after 10 recycles, while the relative activity of YADH in silica-coated alginate gel beads was 81.3%. The recycling stability of YADH in silica-coated alginate gel beads was found to be increased significantly mainly due to the effective inhibition of enzyme leakage by compact silica film. PMID- 17274453 TI - Electrospun PHBV/collagen composite nanofibrous scaffolds for tissue engineering. AB - Electrospinning has recently emerged as a leading technique for the formation of nanofibrous structures made of synthetic and natural extracellular matrix components. In this study, nanofibrous scaffolds were obtained by electrospinning a combination of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and type-I collagen in 1,1,1,3,3,3-hexafluoro-2-isopropanol (HIFP). The resulting fibers ranged from 300 to 600 nm in diameter. Their surfaces were characterized by attenuated total reflection Fourier transform infrared spectroscopy, electron spectroscopy for chemical analysis and atomic force microscopy. The PHBV and collagen components of the PHBV/collagen nanofibrous scaffold were biodegraded by PHB depolymerase and a type-I collagenase aqueous solution, respectively. The cell culture experiments indicated that the PHBV/collagen nanofibrous scaffold accelerated the adhesion and growth of NIH3T3 cells more effectively than the PHBV nanofibrous scaffold, thus making the former a good scaffold for tissue engineering. PMID- 17274454 TI - Degradation of electrospun PLGA-chitosan/PVA membranes and their cytocompatibility in vitro. AB - Nanofibrious composite poly(lactide-co-glycolide) (PLGA) and chitosan/poly(vinyl alcohol) (PVA) membranes were prepared by simultaneously electrospinning PLGA and chitosan/PVA from two different syringes. The in vitro degradation of PLGA and cross-linked composite membranes was examined for up to 10 weeks in phosphate buffered saline (PBS, pH 7.4) at 37 degrees C. The pH of PBS, the weight average molecular weight of PLGA, fiber morphology and mechanical properties, including tensile strength, Young's modulus and elongation-at-break, were measured as a function of degradation time. The fibrous composite membranes were further investigated as a promising scaffold for human embryo skin fibroblasts (hESFs) culture. The cell adhesion and morphology of hESFs seeded on each electrospun membrane was observed using scanning electron microscope and inverted phase contrast microscopy after Wright-Giemsa staining. The introduction of chitosan/PVA component changed the hydrophilic/hydrophobic balance and, thus, influenced degradation behavior and mechanical properties of the composite membranes during degradation. The cells could not only favorably attach and grow well on the composite membranes, but were also able to migrate and infiltrate the membranes. Therefore, the results suggest that the composite membranes can positively mimic the structure of natural extracellular matrices and have the potential for application as three-dimensional tissue-engineering scaffolds. PMID- 17274455 TI - Poly(L-lactic acid)/hydroxyapatite hybrid nanofibrous scaffolds prepared by electrospinning. AB - Poly(L-lactic acid)/hydroxyapatite hybrid nanofibrous scaffolds were prepared via electrospinning. The structure and morphology of the scaffolds were investigated using scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy. The experimental results showed that the average diameter of hybrid nanofiber was similar to that of pure poly(L-lactic acid) fiber, but a new surface bonding (COO-) was formed in hybrid nanofiber which made the surface of the fiber coarse. The weight loss and water uptake of pure poly(L lactic acid) scaffolds increased continuously and the viscosity-average molecular weight decreased in the phosphate buffer solution as time passed, while those of hybrid scaffolds were very much slowed down because the dissolving of hydroxyapatite particles acted as a physical barrier and blocked off the entry of water. The biocompatibility of the scaffold has been investigated by human osteosarcoma MG-63 cell culture on the scaffold. The preliminary results showed that cells were well adhered and proliferated better on the hybrid scaffolds than pure scaffolds. PMID- 17274457 TI - Portuguese Familial Hypercholesterolemia Study: presentation of the study and preliminary results. AB - INTRODUCTION: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder caused, in the majority of cases, by a partial or total lack of functional low density lipoprotein receptors (LDLR). Mutations in the LDLR gene lead to increased plasma cholesterol levels, resulting in cholesterol deposition in the arteries, thereby increasing the risk of premature coronary heart disease. The homozygous form of FH is rare but heterozygous FH is common, although underdiagnosed in many populations, including the Portuguese. In 1999 the Portuguese Familial Hypercholesterolemia Study was begun at the National Institute of Health. OBJECTIVES: The aim of the Portuguese Familial H ypercholesterolemia Study is to perform an epidemiological study to determine the prevalence and distribution of FH in Portugal and to better understand the pathophysiology of coronary heart disease in these patients. The aim of the present work is to present the study's criteria and organization as well as its preliminary results. METHODS: The study population consists of individuals of both sexes and all ages with a clinical diagnosis of FH, with biochemical and molecular characterization being performed. The clinical criteria used for the diagnosis of FH were adapted from those of the Simon Broome Heart Research Trust. The study is organized in five stages: 1. selection of individuals with a clinical diagnosis of FH; 2. completion of a clinical questionnaire and declaration of informed consent; 3. collection of blood samples; 4. biochemical characterization; 5. molecular study of three genes associated with the FH phenotype: LDLR, apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). RESULTS: Between 1999 and June 2006 the LDLR gene and the APOB gene of 141 index cases (38 children and 103 adults) were studied. In 78 of these index cases (76 heterozygotes and two homozygotes) 50 different mutations in the LDLR gene were identified, and two unrelated individuals were found to have the ApoB3500 mutation. The PCSK9 gene was also studied in individuals in whom a mutation in the LDLR or APOB genes was not found, which identified two index cases with a mutation in this gene. The study of 62 families led to the identification of an additional 117 individuals with FH, 90 adults and 27 children (86 adults and 27 children with mutations in the LDLR gene, two adults with the ApoB3500 mutation, and two adults with a mutation in the PCSK9 gene). CONCLUSIONS: Genetic diagnosis enables correct identification of the disease and provides the basis for more aggressive pharmacologic therapeutic interventions to reduce cardiovascular risk in affected individuals. At present thirteen clinicians are collaborating in the Portuguese FH Study, but it is extremely important to obtain the collaboration of more physicians throughout the country, so that the prevalence and distribution of FH in the Portuguese population can be characterized and a greater number of individuals can benefit from appropriate and early therapy. PMID- 17274456 TI - Effect of physical exercise on markers of acute cardiotoxicity induced by d amphetamine in an animal model. AB - Twenty-four mice (male, 8 weeks) were divided equally into four groups: Control (GC), Amphetamine (GAnf), Exercise (GEx) and Exercise with Amphetamine (GExAnf). The protocol began with i.p. administration of 0.1 ml saline solution (to GC and GEx) and 20 mg/kg d-amphetamine dissolved in 0.1 ml saline solution (to GAnf and GExAnf). Immediately afterwards, GEx and GExAnf started exercise (swimming, 60 min at 37 degrtees C). At the same time GC and GAnf were immersed in shallow water (60 min at 37 degrees C, without exercise). Subcutaneous temperature was measured every 15 minutes, and the animals were sacrificed 60 min after the i.p. injection, with cardiac muscle tissue harvested for histological analysis and quantification of oxidized and reduced glutathione (GSSG and GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl groups. Body temperature remained constant during the protocol, in all groups. GC and GEx exhibited normal histology, whereas GAnf exhibited the most marked histological changes. GSH levels were higher (p < 0.05) in GEx and GExAnf (vs. GC and GAnf respectively) with similar % GSSG in all groups. TBARS content was also similar in all groups; carbonyl groups were higher (p < 0.05) in GEx (122 +/- 7) and GExAnf (129 +/- 9) compared to GC (100 +/-7 ) and GAnf (114 +/-7). Carbonyl group levels were significantly higher in GAnf than in GC. Administration of 20 mg/kg of d amphetamine produced histological signs of cardiotoxicity, which were not enhanced by physical exercise; however, the combined action of d-amphetamine and physical exercise significantly aggravated protein oxidation markers. PMID- 17274458 TI - Familial hypercholesterolemia and health information systems. PMID- 17274459 TI - Constrictive pericarditis of tuberculous etiology in the HIV-positive patient: case report and review of the literature. AB - Pericardial inflammation secondary to Mycobacterium tuberculosis infection is a rare condition, but its incidence is increasing in parallel with human immunodeficiency virus infection. Recrudescence of various types of tuberculosis should alert the clinician to the possibility of tuberculous pericarditis. The authors present the case of a 27-year-old white male, seropositive for the human immunodeficiency virus, presenting with large volume pericardial effusion and unusual echocardiographic features, global heart failure and clinical suspicion of tuberculosis. After anti-tuberculous chemotherapy and systemic corticosteroids there was some clinical improvement but evolution to constriction. The patient underwent pericardiectomy with good results. The authors present a literature review on constrictive tuberculous pericarditis in human immunodeficiency virus seropositive and seronegative patients, discussing the role of corticosteroids and the contribution of different diagnostic tools. PMID- 17274461 TI - Arterial endothelium and atherothrombogenesis. I--Intact endothelium in vascular and blood homeostasis. AB - Normal endothelium constitutes a physical and biological barrier between the blood and the vascular wall, and also acts as a sensor and transducer of various endogenous and exogenous factors that modulate the blood circulation. Endothelial activity in a given individual at any particular moment reflects the balance between cardiovascular risk factors, genetic predisposition and vascular protection mechanisms. The availability and activity of endothelium-derived nitric oxide (NO) is a major factor in these mechanisms. Further, vasoactive substances synthesized by the vascular wall and/or by blood cells may affect the behavior of the blood-endothelium interface. Vasomotricity is dependent on the balance between vasodilator substances (particularly prostacylin) and vasoconstrictor products (mainly endothelin-1 and angiotensin II). The coagulation-anticoagulation or fibrinolysis balance is also affected by various different proteins. The mechanisms of these factors, on which blood fluidity depends under normal conditions and with intact endothelium, are discussed, along with mention of potential abnormalities, which will be examined in the second part of this review. PMID- 17274460 TI - Cardiovascular protection from alcoholic drinks: scientific basis of the French Paradox. AB - This article discusses the cardiovascular protection afforded by low to moderate consumption of ethanol and the role of ethanol-induced preconditioning. Ethanol, a compound that is found in many popular beverages, has a whole range of cardiovascular protective effects when consumed in low to moderate doses. Although they have yet to be totally clarified, recent data suggest that a combination of several actions at the biochemical and molecular levels play a role in this protection. These include favorable changes in lipid metabolism, antioxidant effects, changes in hemostasis and platelet aggregation, arterial vasodilation mediated by NO release, induction of the expression of cardioprotective proteins, insulin sensitization and lower levels of inflammatory markers. Special emphasis will be given to ethanol-induced preconditioning. Some of the compounds present in red and white wine, such as resveratrol and quercetin, are also partly responsible for some of the cardioprotective effects of alcoholic drinks. These are due to antioxidant effects and changes in platelet aggregation, endothelial function and inflammatory response. The last part of the paper will focus on the clinical applications and possibilities raised by these new findings. PMID- 17274462 TI - Percutaneous embolization of coronary fistula--case report. PMID- 17274463 TI - Pharmacological block of autonomic activity in a patient with paroxysm atrial fibrillation. PMID- 17274464 TI - [Determinants of therapeutical success of percutaneous transluminal renal angioplasty in patients with hypertension caused by atherosclerotic renal artery stenosis]. PMID- 17274465 TI - [Allelic variants of genes: angiotensin I-converting enzyme (ACE), angiotensin-II type 1 receptor (AT1R), methylenetetrahydrofolate reductase and left ventricular mass in patients with myocardial infarction]. AB - BACKGROUND: Ischemic heart disease has a complex etiology apparently involving gene polymorphisms in the renin-angiotensin system. I/D ACE, A11166C AT1R and C677T MTHFR polymorphisms seem to be associated with a higher risk of myocardial infarction. The aim of this study was to establish the distribution of ACE, AT1R and MTHFR genotypes, and search for correlations with left ventricular anatomic measurements in Polish patients with a history of myocardial infarction. INVESTIGATED GROUP AND METHOD: Our study group comprised 100 patients (14 females and 86 males, aged 54.2 +/- 9.2 years) and 100 age-matched controls (10 females and 90 males, aged 52.3 +/- 10.0 years). We used PCR and PRC-RFLP to detect ACE I/D, AT1RAl 166C and MTHFR C677T gene polymorphisms, respectively. RESULTS: Distribution of individual genotypes did not differ significantly ACE, AT1R, MTHFR in study vs. control groups. No association between ACE, AT1R or MTHFR genotypes and left ventricular mass was found. CONCLUSIONS: Our results suggest that polymorphisms of the ACE, AT1R and MTHFR genes do not predispose to myocardial infarction and higher left ventricular mass in the Polish population. PMID- 17274466 TI - [The influence of selected nonsteroidal anti-inflammatory drugs on antioxidative enzymes activity]. AB - Three nonsteroidal anti-inflammatory drugs were tested: two inhibitors of COX-1 and COX-2 (acetylosalicylic acid and diclofenac), one inhibitor of COX-2 (nimesulid) and superoxide dismutase, catalase and glutatione peroxidase activity was estimated. The investigations were carried out in rats fed by gastric tube for three weeks with acetylsalicylic acid in doses of 2 and 10 mg/kg body weight, diclofenac in doses 1 and 5 mg/kg body weight and nimesulid in doses 2.5 and 12.5 mg/kg body weight. The results were compared with a control group of rats which obtained water into the stomach. No statistically characteristic changes of superoxide dismutase activity were observed. Catalase activity was statistically decreased after both doses of nimesulid and acetylsalicylic acid at the dose of 10 mg/kg body weight. Both doses of diclofenac increased catalase activity. Glutatione peroxidase activity was statistically decreased after both doses of nimesulid and in the dose 10 mg/kg body weight of acetylsalicylic acid and in the dose 5 mg/kg body weight of diclofenac. PMID- 17274467 TI - [Hyperandrogenism as a risk factor of coronary artery disease in young women]. AB - The aim of the study was an attempt to assess the relative roles of common risk factors of coronary artery disease (CAD) and sex hormones in the pathogenesis of CAD in young menstruating women. 38 women in the age of 35-47 years with past myocardial infarction and angiographically proven critical changes in coronary arteries, with one-vessel disease in 22 women (58%) or multi-vessel disease in 16 (42%) were examined. A referee group consisted of 15 healthy women in the age of 35-45 years. In all women multiple risk factors were searched, including value of body mass index (BMI) and waist-hip ratio (WHR). In 4-7 day of sexual cycle at 8.00 a.m. blood from cubital vein was taken to measure concentrations of biochemical parameters and hormones: estradiol, testosterone (T), dehydroepiandrosterone sulphate, folliclestimulating hormone, luteinizing hormone, prolactin, thyreotropin, progesterone, cortisol and sex-hormone binding globulin. In women with CAD, comparing to healthy ones, a higher frequency of arterial hypertension (55% vs 7%), cigarete smoking (95% vs. 46%), hirsutism (84% vs. 30%) and dyslipidaemia was found. Concentration of T was significantly higher in women with CAD than in healthy women (3.5 +/- 1.5 nmol/l--vs. 2.4 +/- 1.0, p < 0.014). In regression analysis was revealed that in multiple parameters a cluster of 2 parameters, dyslipidaemia and hirsutism, was of the best goodness of fit with occurence of CAD. Significant relation with CAD was proven for visceral obesity, eleveted concentration of T and cigarette smoking, either. Conclusions. Apart from common known risk factors as visceral obesity, dyslipidaemia and cigarette smoking it is hiperandrogenism that may participate in pathogenesis of CAD in women in the reproductive age. PMID- 17274469 TI - [Higher incidence of type 1 diabetes in males--a study in teenagers and young adults in Krakow region in 1987-1999]. AB - Numerous reports of increasing incidence of type 1 diabetes worldwide, and similar tendency in children population in Poland prompted the study aiming at evaluating the incidence of type 1 diabetes in a population aged 15-29 years in Krakow area (voivodeship) in 1987-1999. The type 1 diabetes registry established in Chair and Department of Endocrinology CMUJ in 1986 was continued. To improve ascertainment two independent data sources were used: hospital departments and outpatient diabetic clinics. Definite inclusion criteria were assigned and data verified. Incidence rates and trends of incidence were calculated for gender and age groups, differences between the groups were analyzed. Incidence rates were standardized for the European population. The seasonality of disease occurrence was calculated. Registry ascertainment was assessed using "capture-recapture" method. Incidence of type 1 diabetes showed a significant increase in the whole group (0.32 new cases/100,000/year), mainly due to marked incidence increase observed in males (0.53). The oldest age group (25-29 years) showed the most rapid increase in diabetes type 1 incidence (1.07). Seasonality of disease occurrence was found in females. Mean ascertainment was 81%, with the lowest values in 1996-1999. The results obtained indicate that the increase of type 1 diabetes incidence in the age group 15-29 years in Krakow region was due to rapidly increasing incidence in males, especially those aged 25-29 years. Lack of disease occurrence seasonality in this group may indicate a role of other factors (associated with lifestyle or hormonal) responsible for such marked increase in young males, not seen in females. The study was terminated in 1999 due to new administrative division of the country and problems with data collection from the area of non-longer existing Krakow voivodeship. PMID- 17274468 TI - [Estimation of renal function in patients with normal serum creatinine undergoing primary percutaneous coronary intervention]. AB - Kidney disease and cardiovascular disease seem to be lethally synergistic and both approach level of epidemy. On the other hand, patients with ischemic heart disease often exhibit renal dysfunction due to concomitant diabetes, hypertension, congestive heart failure and dyslipidemia. Patients with chronic kidney disease are at increased risk of death after acute MI. AIM: Assessment of prevalence of kidney dysfunction in patients with normal serum creatinine using estimated GFR in a cohort of 922 consecutive patients undergoing primary PCI due to acute myocardial infarction. RESULTS: Normal serum creatinine (less than 1.5 mg/dL in males and less than 1.2 mg/dL in females) was observed in 857 (93%) patients. Mean GFR was 69.0 +/- 21.15 ml/min (Cockcroft-Gault formula), 85.18 +/- 24.17 ml/min (MDRD) or 72.25 +/- 21.65 ml/min (Jeliffe). According to Cockcroft Gault formula stage 2 chronic kidney disease-CKD i.e. GFR 60-89 ml/min was found in 378 patients (44.11%) and stage 3 CKD i.e. GFR 30-59 ml/min was found in 283 (33.02%) patients with normal serum creatinine. According to MDRD formula stage 2 CKD was found in 440 patients (51.32%) and stage 3 CKD was found in 71 (8.29%) patients, whereas according to Jeliffe formula stage 2 CKD was found in 405 patients (47.25%) and stage 3 CKD was found in 194 (22.63%) patients with normal serum creatinine. CONCLUSION: The prevalence of chronic kidney disease is high, up to almost 80% patients undergoing primary PCI despite normal serum creatinine. The risk of contrast nephropathy with worse outcomes is enhanced in these patients. In patients with risk factors for cardiovascular disease, GFR should be estimated since renal dysfunction is one more important risk for cardiovascular morbidity and mortality. PMID- 17274471 TI - [Madelung disease--case report]. AB - Madelung disease-benign symetric lipomatosis--is uncommon condition affecting adults in age 30-60 years, characterized by symmetric accumulation of fatty tissue in the neck (type I), and upper back, shoulder girdle (type II). Type III is described as disproportionate accomodation of subcutaneous tissue in pelvic gridle. Pathogenesis of this disorder is not recognized well, but one of the most common risk factor is an alcohol consumption. In this paper a case of 60 years old man is described. Lipomatosis of neck started as single nodulus 6 years ago, and led to severe decrese of neck movements. As diagnosis has been established, the patient was surgicaly treated with good results. PMID- 17274470 TI - [Three cases of suicidal morbital intoxication--preparation for euthanasia of small animals]. AB - Three cases of suicidal Morbital intoxication were presented. Morbital is a veterinarian preparation for euthanasia of small animals. This preparation is an injectable solution containing 26.7 mg pentobarbitone and 133.3 mg pentobarbitone sodium per 1 ml. In cases no 1 and no 2 the drug was administered by intravenous self-injection, in case No 3--by oral administration. In all cases the suicide was attempted after alcohol consumption. In the first case only confusion and equilibrium disorder were observed. In the second case coma and flaccidity with hyporeflexia were noted. In the first two cases the blood barbiturates concentration was low (1.46 and 1.42 microg/ml), in addition in case No 2 high benzodiazepine serum concentration was revealed (451.64 ng/m). Because of that, it was concluded that in case No 2 severe patients condition resulted from a mixed intoxication with pentobarbitone, benzodiazepines and ethanol. In the case no 3 deep coma, hypotension and circulatory insufficiency were observed. The blood barbiturates concentration was high (10.14 microg/ml). After 4 days barbiturate serum concentration was dropped and the patient developed symptoms of central nervous system (CNS) injury. The computer tomography showed intracranial hematoma in frontal lobe. Based on these results and history obtained from patients mother it was assumed that the intracranial bleeding is most probably of traumatic etiology. After a neurosurgical consult the patient was transferred to neurology word in order to continue medical treatment. Probably high pentobarbitone concentration in the first three days of hospitalisation was the cause of absence of CNS injury symptoms because diminution of high intracranial pressure associated with hematoma. In all cases the mainstay of therapy was forced diuresis and supportive care (airway protection, mechanical ventilation, vasopressors). No extracorporeal methods of toxin elimination from the blood were used. This paper indicates that self-administration of Morbital-preparation for euthanasia of small animals, may evoke severe intoxication in man. PMID- 17274472 TI - [The role of endothelial lipase in the pathogenesis of atherosclerosis]. PMID- 17274473 TI - [Silent myocardial ischemia]. PMID- 17274475 TI - [Non-alcoholic fatty liver disease]. PMID- 17274474 TI - [Application of ATG, anti-CD3, anti-CD52 and anti-CD20 antibodies to transplantation]. PMID- 17274476 TI - Pharmacy benefit management standards moving the industry forward. PMID- 17274477 TI - The future of drug product selection in health care and the role of the pharmacy and therapeutics committee. PMID- 17274478 TI - Formulary implications of management of pulmonary arterial Hypertension: Part II- Payer and provider perspectives on new therapeutic options. AB - In this two-part white paper from The Pharmacy and Therapeutics Society, the authors have described a number of potent oral therapies available or in late clinical development for the treatment of pulmonary arterial hypertension (PAH). They assert that for optimal clinical efficacy and cost efficiency, patients with PAH should be managed, and treatment initiated, within specialist tertiary referral centers. Combination therapy using oral agents with complementary mechanisms of action may offer increased clinical efficacy over monotherapy and reduce the need for parenteral therapy; however, combination therapy may be limited by clinically significant interaction between these agents, such as in the case of bosentan and sildenafil. Newer treatments may offer less potential for liver damage and more favorable interaction profiles. PMID- 17274479 TI - Cost effectiveness of topiramate in the prevention of migraines in the United States: an update. AB - A previously published decision-analytic model assessing the clinical and economic consequences of topiramate versus no preventive treatment in migraineurs was updated with new published literature and unpublished clinical trial data. The model captured baseline migraine days, treatment discontinuation, treatment response (i.e., > or = 75%, 50%-74%, and < 50% reduction in migraine frequency), hours of disability, cost of preventive therapy, cost of acute treatment (pharmacy and medical service), and wages. Topiramate was associated with 29 fewer migraine-days and 78 fewer hours of disability per year, compared with no preventive treatment. The incremental cost per migraine-day averted for topiramate versus no preventive treatment was dollar 29 when only direct medical costs were considered and dollar 2 when total costs were included. Model results were sensitive to baseline migraine-days, response probability, and probability of an attack being treated with a triptan. Topiramate may be a cost-effective treatment for the prevention of migraine. PMID- 17274480 TI - Integrated pharmacy benefit managers: back to the future? PMID- 17274481 TI - Direct medical costs of constipation in the United States. AB - This study estimated the total medical cost of care and described characteristics of patients with constipation in the United States. The 2001 National Ambulatory Medical Care Survey, National Hospital Ambulatory Medical Care Survey, and National Hospital Discharge Survey were used to provide national estimates. Patients diagnosed with constipation, or whose constipation was a reason for the visit, were identified. Medicare reimbursement rates based on recognized diagnostic and procedural codes were used to value each visit related to constipation. Constipation was a diagnosis or reason for seeking care in an estimated 5.7 million ambulatory visits and was the primary diagnosis or reason for 2.7 million of those visits. Of these visits, 1,838,493 were outpatient physician, 297,927 were outpatient hospital, and 555,432 were emergency department. Constipation was the primary diagnosis in 38,361 additional inpatient visits. Total cost was dollar 235 million per year, with 55% incurred from inpatient care and 23%, 16%, and 6% from ED, outpatient physician, and outpatient hospital settings, respectively. Constipation is treated primarily in ambulatory settings, but the costs of inpatient care exceed those of ambulatory care. PMID- 17274482 TI - California prohibits balance billing against HMO members. PMID- 17274483 TI - The Democratic Party's National Platform on Health Care. PMID- 17274484 TI - Is acupuncture more effective than conventional therapy in improving pain and functionality for osteoarthritis of the knee? PMID- 17274486 TI - G. Heiner Sell memorial lecture: neuronal plasticity after spinal cord injury: significance for present and future treatments. AB - Recent progress in the understanding of movement control allows us to define more precisely the requirements for successful rehabilitation of patients with neurologic deficits after a spinal cord injury (SCI). Load- and hip joint position-related afferent input seems to be of crucial importance for the generation and success of locomotor training. In addition, there is accumulating evidence from animal experiments that axonal regeneration can be induced after a SCI. Consequently, in the near future, new therapeutic approaches will be developed for the treatment of subjects with SCI. Functional training and regeneration represent complimentary approaches. Regenerating spinal tract fibers needs functional training to make the appropriate connections, and training effects will be enhanced by regenerating fibers. A clinical basis for monitoring the effects of novel interventional therapies is needed. Refined and combined clinical and neurophysiologic measures are needed for a precise qualitative and quantitative assessment of spinal cord function in patients with SCI at an early stage. This is a basic requirement for predicting functional outcome, as well as for recognizing any improvement in the recovery of function caused by a new treatment. To this aim, 14 European spinal cord injury centers involved in the rehabilitation of patients with acute SCI have built a close clinical collaboration using a standardized protocol for the assessment of the outcome after SCI and the extent of recovery achieved by actually applied therapies in a larger population of patients with SCI. PMID- 17274488 TI - Incidence, etiology, and risk factors for fever following acute spinal cord injury. AB - OBJECTIVE: To identify the incidence, etiology, and risk factors for fevers in individuals with traumatic spinal cord injury (SCI). DESIGN: A retrospective review of the medical records of consecutive adult traumatic SCI patients over a 2-year period was performed. SETTING: The study was performed at a tertiary care, Level I trauma center. PARTICIPANTS: Consecutive adult traumatic SCI admissions to acute care (n = 48) and rehabilitation (n = 40) were included in the study. MAIN OUTCOME MEASURES: Incidence, etiology, mean maximum temperature elevation, and duration of fevers (temperature >99.9 F) were measured. RESULTS: The incidence of fever was 60.4% and 50% (acute care and rehabilitation, respectively). Total number of fevers was 58 and 66, acute and rehabilitation, respectively. Respiratory and urinary tract were the most common identifiable fever etiologies. Unidentified fever etiologies were numerous in both the acute and rehabilitation groups, representing 66% and 56% of cases, respectively. Significant differences (P < 0.05) were found between identified vs unidentified fever etiology groups for mean maximal temperature (102.5 degrees F vs 101.1 degrees F on acute and 101.5 degrees F vs 100.7 degrees F on rehabilitation), duration of fever (10.3 days vs 2.2 on acute and 2.8 days vs 1.3 on rehabilitation), fevers above 101.4 degrees F (75% vs 29% on acute and 40% vs 8% on rehabilitation), cause of injury (gunshot wound on acute care) and completeness of injury (American Spinal Injury Association classification A on rehabilitation). CONCLUSIONS: This study suggests that fevers occur commonly in patients with SCI, with respiratory and genitourinary system etiologies most commonly identified. Unidentified etiologies were common and were associated with lower temperature elevation and shorter fever duration. Injury etiology and completeness of injury may comprise additional risk factors. These factors should be taken into account when initiating cost-efficient fever workup in individuals with SCI. PMID- 17274489 TI - Fibrinogen metabolism in patients with spinal cord injury. AB - BACKGROUND/OBJECTIVE: Deep venous thrombosis and pulmonary thromboembolism are common within weeks of spinal cord injury (SCI) but clinically uncommon in the chronically paralyzed. Fibrinogen half-life (FHL) and fibrin uptake of the legs (FUT), as indicators of an active thrombotic process, have been used to test this clinical impression. METHODS: Data from the use of autologous preparations of radioiodinated fibrinogen to determine FHL and FUT in 17 men paralyzed at cervical (6), thoracic (10), and lumbar levels (1), at ASIA grades A (15) and C (2) in 1974 to 1976 were reviewed. Group A consisted of 12 subjects 29 +/- 8 years of age and paralyzed 1 week to 5 months (median, 1 month). Group B consisted of 5 subjects 46 +/- 17 years of age and paralyzed 24 to 96 months (median, 36 months). Group B subjects were older and paralyzed longer than Group A. Group C consisted of 4 able-bodied control subjects enrolled at the same time for FHL studies, and these subjects were 34 to 38 years of age. RESULTS: FHL was 61 +/- 14 hours for all SCI subjects and 95 +/- 23 hours for Group C (P = 0.001). Group A FHL was 59 +/- 16 hours, and FUT was positive in 8 of 12 subjects. Group B FHL was 66 +/- 7 hours, and FUT was positive in 3 of 4 subjects (1 FUT not done; P = 0.30 and 1.0, respectively). CONCLUSIONS: Fibrinogen metabolism was abnormal in patients with acute SCI at high risk for pulmonary thromboembolism (PE) but continued to be abnormal beyond the high risk period for PE, possibly because of the greater age of the patients in the long-term paralysis group. PMID- 17274487 TI - Bone loss and muscle atrophy in spinal cord injury: epidemiology, fracture prediction, and rehabilitation strategies. AB - Individuals with spinal cord injury (SCI) often experience bone loss and muscle atrophy. Muscle atrophy can result in reduced metabolic rate and increase the risk of metabolic disorders. Sublesional osteoporosis predisposes individuals with SCI to an increased risk of low-trauma fracture. Fractures in people with SCI have been reported during transfers from bed to chair, and while being turned in bed. The bone loss and muscle atrophy that occur after SCI are substantial and may be influenced by factors such as completeness of injury or time postinjury. A number of interventions, including standing, electrically stimulated cycling or resistance training, and walking exercises have been explored with the aim of reducing bone loss and/or increasing bone mass and muscle mass in individuals with SCI. Exercise with electrical stimulation appears to increase muscle mass and/or prevent atrophy, but studies investigating its effect on bone are conflicting. Several methodological limitations in exercise studies with individuals with SCI to date limit our ability to confirm the utility of exercise for improving skeletal status. The impact of standing or walking exercises on muscle and bone has not been well established. Future research should carefully consider the study design, skeletal measurement sites, and the measurement techniques used in order to facilitate sound conclusions. PMID- 17274490 TI - Long-term survival of persons ventilator dependent after spinal cord injury. AB - BACKGROUND/OBJECTIVE: Identify factors related to long-term survival, and quantify their effect on mortality and life expectancy. SETTING: Model spinal cord injury systems of care across the United States. STUDY DESIGN: Survival analysis of persons with traumatic spinal cord injury who are ventilator dependent at discharge from inpatient rehabilitation and who survive at least 1 year after injury. METHODS: Logistic regression analysis on a data set of 1,986 person-years occurring among 319 individuals injured from 1973 through 2003. RESULTS: The key factors related to long-term survival were age, time since injury, neurologic level, and degree of completeness of injury. The life expectancies were modestly lower than previous estimates. Pneumonia and other respiratory conditions remain the leading cause of death but account for only 31% of deaths of known causes. CONCLUSIONS: Whereas previous research has suggested a dramatic improvement in survival over the last few decades in this population, this is only the case during the critical first few years after injury. There was no evidence for such a trend in the subsequent period. PMID- 17274491 TI - Changes in the biochemical profiles of mid-cervically located adenosine A1 receptors after repeated theophylline administration in adult rats. AB - BACKGROUND/OBJECTIVE: Adenosine A1 receptors localized in the phrenic motoneurons (PMNs), where the axons of the descending bulbospinal respiratory make synaptic contacts, may be involved in theophylline-induced respiratory-related activity in rats. The objective of this study was to characterize the biochemical profiles of adenosine A1 receptors in 2 groups of rats: (a) naive and (b) theophylline treated (3-day oral administration). METHODS: Biochemical binding characteristics of adenosine A1 receptors in the C3 to C5 (PMN) of adult rats were assessed in naive (n = 6) and theophylline-treated animals (n = 6) using [3H]-DPCPX (10 pmol/L to 30 nmol/L), the specific adenosine A1 receptor antagonist in saturation binding assays. Competition assays used theophylline as the competing ligand (20 mmol/L to 20 pmol/L), and protein concentration was determined with the Bradford assay using a range of standards (0.016-1.0 mg/mL). RESULTS: In saturation binding assays in naive animals, the A1 receptor was characterized by a single binding site with Bmax and Kd values of 256.00 +/- 32.13 fmol/mg protein and 2.89 +/- 0.45 nmol/L, respectively. Analysis of the isotherm in theophylline-treated animals showed 1 site with Bmax and Kd values of 219.00 +/- 26.3 fmol/mg protein and 0.60 +/- 0.21 nmol/L, respectively, and a second site characterized by Bmax and Kd values of 492.6 +/- 3.15 fmol/mg protein and 14.09 +/- 2.06 nmol/L, respectively. CONCLUSIONS: Theophylline administration revealed 2 binding sites on receptors (characterized by the specific adenosine A1 antagonist, [3H]-DPCPX) located in the vicinity of phrenic motoneurons (C3-C5). Alteration of the receptor profiles after theophylline may underlie the respiratory-related actions of the drug. PMID- 17274493 TI - Menatetrenone (vitamin K2) and bone quality in the treatment of postmenopausal osteoporosis. AB - Menatetrenone (vitamin K2) reduces the incidence of vertebral fractures but has only modest effects on bone mineral density (BMD) in postmenopausal women with osteoporosis. Combined treatment with bisphosphonates and menatetrenone may be more effective than treatment with bisphosphonates alone in preventing vertebral fractures, despite the lack of an additive effect of menatetrenone on the BMD increase by bisphosphonates. Menatetrenone improves bone architecture in ovariectomized rats, and the mineral/ matrix ratio of the bone in terms of matrix volume and bone strength (without increasing bone mass) in rats with magnesium deficiency. Thus, available evidence supports an effect of menatetrenone on bone quality during osteoporosis treatment. PMID- 17274494 TI - Effectiveness of monetary incentives in modifying dietary behavior:a review of randomized, controlled trials. AB - To review research evidence on the effectiveness of monetary incentives in modifying dietary behavior, we conducted a systematic review of randomized, controlled trials (RCTs) identified from electronic bibliographic databases and reference lists of retrieved relevant articles. Studies eligible for inclusion met the following criteria: RCT comparing a form of monetary incentive with a comparative intervention or control; incentives were a central component of the study intervention and their effect was able to be disaggregated from other intervention components; study participants were community-based; and outcome variables included anthropometric or dietary assessment measures. Data were extracted on study populations, setting, interventions, outcome variables, trial duration, and follow-up. Appraisal of trial methodological quality was undertaken based on comparability of baseline characteristics, randomization method, allocation concealment, blinding, follow-up, and use of intention-to-treat analysis. Four RCTs were identified as meeting the inclusion criteria. All four trials demonstrated a positive effect of monetary incentives on food purchases, food consumption, or weight loss. However, the trials had some methodological limitations including small sample sizes and short durations. In addition, no studies to date have assessed effects according to socioeconomic or ethnic group or measured the cost-effectiveness of such schemes. Monetary incentives are a promising strategy to modify dietary behavior, but more research is needed to address the gaps in evidence. In particular, larger, long-term RCTs are needed with population groups at high risk of nutrition-related diseases. PMID- 17274492 TI - Bladder management for adults with spinal cord injury: a clinical practice guideline for health-care providers. PMID- 17274495 TI - Is 9-cis-retinoic acid the endogenous ligand for the retinoic acid-X receptor? AB - Specific proteins in the nucleus act as transcription factors upon activation through binding of small molecules (all-trans-retinoic acid, thyroid hormone, vitamin D, and others). The activated (liganded) receptors bind to specific DNA elements as heterodimers, each in combination with the retinoic acid-X receptor (RXR). 9-Cis-retinoic acid binds to RXR with high affinity and activates it. Though 9-cis-retinoic acid was initially found in animal tissues, in later work 9 cis-retinoic acid could not be detected. A search for a ligand for RXR in tissues showed that unsaturated fatty acids, particularly linoleic, linolenic, and docosahexaenoic acids, bound to and activated RXR as specific ligands, although with low affinity. A critical experiment demonstrated that, at least in developing mouse skin, 9-cis-retinoic acid is not the ligand for RXR. PMID- 17274496 TI - Effect of dietary carbohydrate restriction with and without weight loss on atherogenic dyslipidemia. AB - Increasing evidence suggests a role for carbohydrate restriction in the dietary treatment of atherogenic dyslipidemia. The effects of carbohydrate restriction on the specific aspects of lipoprotein metabolism affected by atherogenic dyslipidemia under weight-stable and weight-loss conditions are reviewed here. PMID- 17274497 TI - [The revival of thalidomide: an old drug with new indications]. AB - Thalidomide has several mechanisms of action: several immuno-modulatory properties, an anti-angiogenic action and a hypnosedative effect. Thalidomide has been used in several cutaneous inflammatory disorders (such as erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus, severe aphtosis), cancers (relapsed/refractory multiple myeloma) and inflammatory conditions. Several side effects are associated with thalidomide; some are major: teratogenicity, peripheral neuropathy and deep venous thrombosis; some are minor, such as somnolence or abdominal pain and endocrinologic disturbances. Use of thalidomide is strictly controlled with close adherence to a birth control program and close monitoring for early development of peripheral neuropathy. PMID- 17274498 TI - [Treatment delay and bone destruction in basal cell carcinoma]. PMID- 17274499 TI - [Supportive care for people affected by cancer. We all are concerned]. PMID- 17274500 TI - [Supportive care for people affected by cancer: concept and management]. AB - The concept of continuous and global care is acknowledged today by all as inherent to modern medicine. The supportive care are defined as "all care and supports necessary for ill people, at the same time as specific treatments, along all severe illnesses". This definition integrates as much the field of curative care, cure with possible after-effects as that of palliative care. A supportive care coordination is justified by the pluridisciplinarity and hyperspecialisation of the professionals, by a poor communication between the teams, by the administrative difficulties encountered by the teams participating in the supportive care. Supportive care is not a new speciality. They are a coordinated organisation with a "basic coordination" involving the activities of chronic pain, palliative care, psycho-oncology, nutrition, and social care... PMID- 17274501 TI - [Breaking bad news: cancer diagnosis]. AB - The announcement of cancer diagnosis is always a traumatic state. For a long time, the physicians have been embarrassed to cope with emotional behaviours of their patients and received not enough help. In France, the "Plan Cancer" tries to organize the time of announcement. It constitutes an overhang which doesn't have to lead to imagine the existence of an "easy and simple solution". Psycho oncology tries to support patients and medical staffs and must help everyone to understand expectations and limits in this field. PMID- 17274502 TI - [Management of pain induced by invasive procedures in oncology]. AB - Pain management is a priority issue in oncology. However, pain induced by invasive procedures, notably diagnostic procedures, remains largely underexplored. We will first describe the various procedures that cause pain in oncology (venous or arterial puncture, bone marrow harvest and biopsy, wound dressing, pulling of drains...). We then will propose strategies to manage such pain, based on the rather scarce information drawn from the international literature. Auto-evaluation of pain by the patient, good technical practice and comforting attitude of the caregiver are prerequisites for these strategies. Local anaesthesia, use of fixed 50% nitrous oxide oxygen mixture, analgesics and tranquilizers have also proven helpful. Further evaluation is needed for standardization of these procedures. PMID- 17274503 TI - [Myelotoxicity due to chemotherapy in oncology practice]. AB - Myelotoxicity due to chemotherapy remains important due to its high incidence. It's one of the main toxicities due to medical treatments in oncology. Most regimens continue to be dose limited by this type of toxicity. It may concern red blood cells (anemia), white blood cells (leucopenia and neutropenia) and platelets (thrombocytopenia). The development of hematologic growth factors allows for new approaches and some modifications in the treatment of myelotoxicity. PMID- 17274504 TI - [Nausea and vomiting in cancer patients]. AB - Despite an increasing number of antiemetic drugs available, nausea and vomiting (NV) remain a central problem during chemotherapy. Acute and delayed NV benefit most often from the combination of classical antiemetic (such as metoclopramide or metopimazin), corticosteroids and 5HT3 inhibitors (setrons). Since 2006, a new class of antiemetics are available, the NK1 inhibitors (aprepitant), which improve the control of NV in combination with setrons and corticosteroids. Anticipatory NV must be treated with benzodiazepines. Other causes of NV must be discussed in those patients, such as gastro intestinal or metabolic disorders, cancer evolution such as occlusion, brain metastases. A global approach is necessary to improve the quality of life all along the courses of chemotherapy, including somatic and psychologic aspects. PMID- 17274505 TI - [Chemotherapy-induced alopecia]. AB - Chemotherapy-induced alopecia is frequent with most chemotherapy regimens; mechanisms, evolution and small prevention tools are described. Scalp cooling (helmets or continuous cooling systems) can avoid or diminish hair loss in selected chemotherapy regimens but tolerance can be fair and long harmlessness needs to be confirmed by prospective studies. Drug prevention is only in the first steps of research. PMID- 17274506 TI - [Malnutrition in cancer patients]. AB - Malnutrition is common in cancer patients. Many factors contribute to weight loss: some of them can be related to diminished dietary intake, while others are more associated with metabolic changes induced by systemic inflammatory responses. This is why at a specific phase during the course of development, some cancers will benefit from nutritional support, while in theory, and others will benefit from anti-inflammatory treatment. Parenteral nutrition is indicated for severe malnourished surgical patients and for allogenic stem cell transplant patients. Tube feeding (enteral nutrition) should be considered for patients with a functional gut who are unable to ingest sufficient nutrients orally, for example head and neck cancer patients. The value of dietary counselling and oral nutritional support has not been proven in patients undergoing chemotherapy, which is why it is so difficult to propose recommendations. Some arguments seem to favour parenteral nutrition for patients with bowel obstruction suffering from advanced-stage incurable cancer. As the results of studies following omega-3 fatty acid-enriched oral nutritional support in palliative care patients are inconsistent, these products cannot be recommended. PMID- 17274507 TI - [Return of sexual function after breast cancer]. PMID- 17274508 TI - [Management of fatigue in oncology]. AB - Fatigue associated with cancer may be present at any stage of the disease; its characteristics vary depending on the type and the duration of treatment, the presence of side effects and the reactions from patients. Often associated with other symptoms (pain, nausea, vomiting, anxiety, stress etc.), fatigue affects the daily life of patients as much as or even more than pain. This multi-factored and annoying symptom is linked to physical, cognitive and affective functioning, which must be assessed (Piper fatigue scale). Beside the medical management, nursing research found four efficient interventions to reduce fatigue: educating patients and their families, programming physical conditioning and activities to restore the attention, improving diet, hydration and sleep. The pluridisciplinary management of this symptom is a key factor to a better quality of life. PMID- 17274509 TI - [Returning to work after cancer]. AB - Employees treated for cancer may dread returning to work. They are indeed afraid of what others will think, of their fatigue that has built up throughout treatments, of their memory disorders, as well as of the silence of their colleagues or employers. This return to work should be planned ahead or at least, discussed as much as possible. Though the disease itself cannot be a reason for dismissal, repeated absences from work due to the disease can be. Employees should thus seek counselling from a social worker who will offer them information and support concerning their rights (cessation of work, part-time medical leave etc.) and eventually will guide them through any other procedure (occupational reclassification, acknowledgment of disability, retirement rights etc.). Talking about the return to work is a necessary step: it enables the various professionals to adapt their relationships with patients. PMID- 17274510 TI - [The risk of neutropenia for oncology patients]. PMID- 17274511 TI - [Both sides of Atlantic Ocean]. PMID- 17274512 TI - [Principal complications of pregnancy: genital hemorrhage]. PMID- 17274513 TI - [Polycystic kidneys]. PMID- 17274514 TI - [Evaluation of the severity and monitoring of early complications in burn patients]. PMID- 17274515 TI - [Nosocomial infections]. PMID- 17274516 TI - [Urinary infections in the child and the adult. Leukocyturia ]. PMID- 17274517 TI - [1879, Ernest Besnier inventor of the word "biopsy"]. PMID- 17274519 TI - PT with heat-processed apple peel extract to detect LTP hypersensitivity. AB - BACKGROUND: Allergen-resolved diagnosis of food allergy may be essential in the clinical practice, particularly in patients allergic to foods that may contain both labile and stable allergens. However, presently available diagnostic tests are not useful in this sense. OBJECTIVE: To assess the clinical usefulness of SPT with a heat-processed apple peel extract as an easily available means to detect hypersensitivity to lipid transfer protein (LTP), an extremely stable and potentially hazardous apple allergen. METHODS: Raw and heat-processed (100 degrees C x 10 min) apple peel extract (100 microg/ml) were used to carry out SPT in 23 patients with apple-allergy, 15 of which considered as probably sensitized to labile allergens (Maid 1, Mal d 4) and 8 to stable allergens (Mal d 3, LTP), respectively on the basis of the presence/absence of IgE reactivity to birch pollen. IgE reactivity to the heat-processed apple peel extract was further analyzed by immunoblot. RESULTS: Altogether SPT with raw apple extract scored positive in 20/23 (87%) patients, including 12/15 patients considered as probably sensitized to labile allergens and 8/8 patients considered as probably sensitized to LTP. In contrast, the heat-processed apple extract induced a wheal-and-flare reaction only in the 8 (100%) presumptive LTP reactors. Immunoblot analysis showed IgE reactivity to a 10 kDa protein (LTP) in heat-processed apple extract. CONCLUSION: The heat-resistance of stable apple allergens like LTP can be usefully exploited to prepare extracts for allergen-resolved diagnosis in-vivo. PMID- 17274518 TI - Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs. AB - The long QT syndrome is a rare disease. The prevalence is estimated at 1/5 000 to 1/20,000. Numerous drugs are contra-indicated because they can lengthen the QT interval. A case of pollen allergy in an adolescent with LQTS is described. The possibility to prescribe anti-H1 drugs is reviewed since cases of torsades de pointe and even deaths have been reported for terfenadine and astemizole. Diphenhydramine, orphenadrine and hydroxyzine are contra-indicated. No accidents and no effects on the QT interval have been published for ebastine, fexofenadine, desloratadine and levocetirizine. These anti-H1 drugs could be used with great care, without any association with drugs resulting in low serum potassium level. Azelastine eye drops have been authorized and a routine protection by inhaled corticosteroids during the pollinic period has been advised in this adolescent treated by betablockers. PMID- 17274520 TI - Efficacy and tolerability of high dose sublingual immunotherapy in patients with rhinoconjunctivitis. AB - In a multi-centre, randomized, double-blind, placebo-controlled clinical trial over 3 years high dose sublingual specific immunotherapy with an extract of a 6 grass-pollen mixture showed a highly significant and clinically relevant improvement in patients with grass pollen rhinitis/-conjunctivitis with or without asthma and an increase in allergen specific antibodies (IgG1, IgG4) indicating immunological efficacy. A difference of 46% in mean symptom medication score between active and placebo group was seen. The treatment with the sublingual solution was well tolerated. High dose sublingual immunotherapy can therefore be considered as an efficient therapeutic option in the management of IgE-mediated allergic airway diseases. PMID- 17274521 TI - Chronic sinusitis and atopy: a cross-sectional study. AB - BACKGROUND: The role of allergic sensitization in chronic sinusitis in childhood is currently unclear, as contrasting results were reported in the studies thus far available. OBJECTIVE: We evaluated by a cross-sectional study the prevalence of sensitization to common inhalant allergens in children with chronic sinusitis. METHODS: Among 2200 children referring to our Paediatric out-patient Unit for evaluation of chronic respiratory symptoms, subjects satisfying at least two of major criteria for the definition of chronic sinusitis were recruited, and underwent to allergen sensitization workup by skin prick test (SPT) with common inhalant allergens and total IgE determination. Participants were stratified according to age inferior to three years (Group 1), age between three and six years (Group 2), and age above six years (Group 3) for the purpose of evaluation. RESULTS: In all, 351 children (217 boys, 134 girls, mean age 5.23 ? 2.11 years, range 4-15 years) were available for evaluation and were stratified (27 in Group 1, 261 in Group 2 and 63 in Group 3). Prevalence of both sensitization to at least one inhalant allergen by SPT and of high total IgE was 29.9%. Prevalence of SPT sensitization was significantly different across age groups, with a value of 7.4% in Group 1, 31.4% in Group 2 and 33.3% in Group 3 (p = 0.028), but after adjusting for age, sinusitis and aeroallergen sensitization did not correlate significantly. The difference across groups for high total IgE did not reach statistical significance, with 22.7%, 30.1% and 32.1% for each group respectively. CONCLUSIONS: The prevalence of sensitization to aeroallergens in children with chronic sinusitis is comparable to that of the general paediatric population, as assessed in the Italian arm of the ISAAC study. This does not account for routine investigation for allergy in children diagnosed with such disease. PMID- 17274522 TI - Anaphylaxis to honey in pollinosis to mugwort: a case report. AB - A case of anaphylaxis to honey in a 19 year old female sensitized to Compositae pollen is described. The patient suffered from summer rhinoconjunctivitis since seven years; in January 2006, ten minutes after eating bread and honey she developed angioedema of the lips and tongue, runny nose, cough, dyspnoea, and collapse, requiring hospitalization and treatment with high dose corticosteroids and anti-histamines. After two weeks, skin prick tests (SPT) with a standard panel of inhalant allergens and prick + prick with a number of kinds of honey were performed. SPTs were positive to mugwort, ragweed, dandelion, and goldenrod. Concerning honey, the prick + prick was positive to "Millefiori" (obtained from bees foraging on Compositae) and also to sunflower, limetree, and gum tree honey, while was negative for other kinds of honey, including the frequently used chestnut honey and acacia honey. The allergenic component responsible of anaphylaxis in this case seems to be a molecule occurring in Compositae pollens, as previously reported for other three reports, but also in pollen from plants of different families. Honey contains a large number of components derived from bees, such as gland secretions and wax, as well as from substances related to their foraging activity, such flower nectar and pollens (1, 2). Honey as a food has been associated to allergic reactions and particularly to anaphylaxis (3-6). Among the pollens, the role of Compositae is somewhat controversial, since its responsibility is clear in some studies (3, 5, 6) but considered negligible in others (7). Here we present the case of a patient sensitized to Compositae pollen who had an anaphylactic reaction to the ingestion of honey obtained from bees foraging on Compositae flowers and was tested with a number of different varieties of honey. PMID- 17274523 TI - Cat-pork syndrome: a case report with a thee years follow-up. AB - A case of cat-pork syndrome with subsequent follow-up in a 17-year-old male patient is reported. At the initial observation, the patient was sensitized to cat epithelium--along with house dust mites and grass pollen--from two years. In 2001 he had an immediate reaction with urticaria, angioedema and dyspnea after eating grilled meat and sausage, and skin tests and CAP/RAST revealed a sensitization to pork meat, with a value of 4.7 KU/L for pork meat, and of 55 KU/L for cat epithelium. The patient was followed up for three years with annual repetition of diagnostic tests. The elimination of pork meat from the diet was incomplete, with slight skin reactions to small amounts of cooked pork meat but tolerance to seasoned pork products such as salami. A challenge test with pork meat in 2004 was positive, with angioedema and asthma symptoms, and CAP/RAST showed a value of 43 KU/L for cat epithelium and 4 KU/L for pork meat. RAST inhibition confirmed the significant cross-reactivity between the two allergen sources. These findings provide some knowledge on the natural history of the cat pork syndrome, and confirm that very prolonged avoidance of the offending foods are needed to expect a loss of sensitization. PMID- 17274524 TI - Molecular basis of neurodegenerative diseases. PMID- 17274525 TI - Biological surfaces as catalysts of amyloid aggregate nucleation and primary sites of amyloid toxicity. AB - The themes of protein folding, misfolding, aggregation and aggregate toxicity to living systems are among the most exciting frontiers in molecular and cell biology as well as in molecular medicine. This is testified by the increasingly higher number of publications on these issues and the debate in the scientific community about some basic questions still unresolved. One of the latter is the role performed in vitro by synthetic and in vivo by biological surfaces in favouring or disfavouring protein folding and misfolding, in speeding the rate of aggregate nucleation and as key targets of toxic aggregates. Indeed, recent research has highlighted the roles of surfaces in all these phenomena; it has also stressed that early oligomeric assemblies in the path of fibrillization are endowed with the highest cytotoxicity and that the latter most likely follows aggregate interaction with cell membrane(s). The resulting membrane destabilization and permeabilization with early alterations in intracellular redox status and ion homeostasis possibly culminates with cell death. Each of these steps is most likely influenced by the physicochemical and biochemical features of the membrane(s) themselves in ways that are still under investigation. This review summarizes the most recent advances in these fields. PMID- 17274526 TI - The cytosolic domain of APP and its possible role in the pathogenesis of Alzheimer's disease. AB - APP is a type I membrane protein of unknown function, whose proteolytic processing, driven by beta- and gamma-secretases, generates the beta-amyloid peptides, one of the hallmarks of the pathogenesis of Alzheimer's disease. The short cytosolic domain of APP is the center of a complex network of protein protein interactions. This network appears to play a crucial role in the regulation of the APP processing and in turn in the generation of the amyloid peptides, thus suggesting candidate targets for new therapeutic approaches. Furthermore, some possible functions of APP could just emerge from the study of this cytodomain and its partners. PMID- 17274527 TI - Copper imbalance and oxidative stress in neurodegeneration. AB - Much experimental evidence demonstrates that the increased production of free radicals and oxidative damage due to alterations in copper homeostasis (because of either deficit or excess or aberrant coordination of the metal) are involved in the neurodegenerative processes occurring in many disorders of the central nervous system. This review outlines the systems that are involved in copper homeostasis and in the control of copper redox reactivity. The mechanisms underlying neurodegeneration in the acknowledged genetic disturbances of copper homeostasis, namely Menkes' and Wilson's diseases, and the involvement of copper in the aetiology of the major neurodegenerative disease of the aging brain, Alzheimer's disease, will be described, with particular focus on oxidative stress. PMID- 17274528 TI - Physiopathologic implications of the structural and functional domains of the prion protein. AB - Prion diseases are invariably fatal neurodegenerative disorders affecting man and various animal species. A large body of evidence supports the notion that the causative agent of these diseases is the prion, which, devoid of nucleic acids, is composed largely, if not entirely, of a conformationally abnormal isoform (PrP(Sc) of the cellular prion protein (PrPc). PrPc is a highly conserved and ubiquitously expressed sialoglycoprotein, the normal function of which is, however, still ill defined. Several modules have been recognised in PrPc structure. Their extensive analysis by different experimental approaches, including transgenic animal models, has allowed to assigning to several modules a putative role in PrPc physiology. Concurrently, it has underscored the possibility that alteration of specific domains may determine the switching from a beneficial role of PrPc into one that becomes detrimental to neurons, and/or promote the conversion of PrPc into the pathogenic PrP(Sc) conformer. PMID- 17274529 TI - Mitochondrial Complex I: structure, function, and implications in neurodegeneration. AB - Mitochondrial Complex I (NADH Coenzyme Q oxidoreductase) is the least understood of respiratory complexes. In this review we emphasize some novel findings on this enzyme that are of relevance to the pathogenesis of neurodegenerative diseases. Besides Coenzyme Q (CoQ), also oxygen may be an electron acceptor from the enzyme, with generation of superoxide radical in the mitochondrial matrix. The site of superoxide generation is debated: we present evidence based on the rational use of several inhibitors that the one-electron donor to oxygen is an iron-sulphur cluster, presumably N2. On this assumption we present a novel mechanism of electron transfer to the acceptor, CoQ. Strong evidence is accumulating that electron transfer from Complex I to Complex III via CoQ is not performed by operation of the CoQ pool but by direct channelling within a super complex including Complex I, Complex III and bound CoQ. Besides structural evidence of a Complex I -Complex III aggregate obtained by native electrophoresis, we have obtained kinetic evidence based on metabolic flux analysis, demonstrating that Complexes I and III behave as an individual enzyme. Quantitative and qualitative changes of phospholipids, including peroxidation, may affect the supercomplex formation. Complex I is deeply involved in pathological changes, including neurodegeneration. Maternally inherited mutations in mitochondrial DNA genes encoding for Complex I subunits are at the basis of Leber's Hereditary Optic Neuropathy; a decrease of electron transfer in the complex, due to the mutations, is not sufficient per se to explain the clinical phenotype, and other factors including proton translocation and oxygen radical generation have been considered of importance. Complex I changes are also involved in more common neurological diseases of the adult and old ages. In this review we discuss Parkinson's disease, where the pathogenic involvement of Complex I is better understood; the accumulated evidence on the mode of action of Complex I inhibitors and their effect on oxygen radical generation is discussed in terms of the aetiology and pathogenesis of the disease. PMID- 17274530 TI - Mutations in structural genes of complex I associated with neurological diseases. AB - This paper summarizes observations on the genetic and biochemical basis of hereditary defects of complex I (NADH-ubiquinone oxidoreductase) of the respiratory chain in human neurological patients. Two different types of functional defects of the complex are described. In one type mutations in the NDUFS1 and NDUFS4 nuclear structural genes of the complex were identified in two unrelated families. Both NDUFS1 and NDUFS4 neurological disorders were transmitted by autosomic recessive inheritance. The two mutations resulted in different impact on cellular metabolism. The NDUFS4 mutation, giving a more severe, fatal pathological pattern, resulted in a defective assembly of the complex and complete suppression of the enzymatic activity. The NDUFS1 mutation, with less severe progressive pathology, caused only partial inhibition of the complex but enhanced production of oxygen free radicals. In the second type of deficiencies extensive mutational analysis did not reveal pathogenic mutations in complex I genes but a decline in the level and activity of complex I, III, and IV were found, apparently associated with alteration in the cardiolipin membrane distribution. PMID- 17274532 TI - The endocannabinoid system in neurodegeneration. AB - Endocannabinoids are bioactive lipids, that comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied endocannabinoids, and act as agonists of cannabinoid receptors. Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol, the psychoactive principle of hashish and marijuana. It is known that the activity of endocannabinoids at their receptors is limited by cellular uptake through specific membrane transporters, followed by intracellular degradation by a fatty acid amide hydrolase (for AEA and partly 2-AG) or by a monoacylglycerol lipase (for 2-AG). Together with AEA, 2-AG and congeners, the proteins that bind, transport and metabolize these lipids form the "endocannabinoid system". This new system will be briefly presented in this review, in order to put in a better perspective the role of the endocannabinoid pathway in neurodegenerative disorders, like Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, the potential exploitation of antagonists of endocannabinoid receptors, or of inhibitors of endocannabinoid metabolism, as next-generation therapeutics will be discussed. PMID- 17274531 TI - Redox regulation of cellular stress response in neurodegenerative disorders. AB - There is increasing evidence that reactive oxygen species (ROS) are not only toxic but play an important role in cellular signaling and in the regulation of gene expression. A number of biochemical and physiologic stimuli, such as perturbation in redox status, expression of misfolded proteins, altered glyc(osyl)ation and glucose deprivation, overloading of products of polyunsaturated fatty acid peroxidation (Hydroxynonenals, HNE) or cholesterol oxidation and decomposition, can disrupt redox homeostasis, impose stress and subsequently lead to accumulation of unfolded or misfolded proteins in brain cells. Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), Amyothrophic lateral sclerosis (ALS) and Friedreich ataxia (FRDA) are major neurological disorders associated with production of abnormal proteins and, as such, belong to the so called "protein conformational diseases". The Central Nervous System has evolved highly specific signaling pathways called the unfolded protein response to cope with the accumulation of unfolded or misfolded proteins. Recent discoveries of the mechanisms of cellular stress signaling have led to major new insights into the diverse processes that are regulated by cellular stress response. Thus, the pathogenic dysfunctional aggregation of proteins in non-native conformations is associated with metabolic derangements and excessive production of ROS. The brain response to detect and control metabolic or oxidative stress is accomplished by a complex network of "longevity assurance processes" integrated to the expression of genes termed vitagenes. Heat shock proteins are a highly conserved system responsible for the preservation and repair of correct protein conformation. Heme oxygenase-1, a inducible and redox regulated enzyme, is currently considered as having an important role in cellular antioxidant defense. A neuroprotective effect, due to its heme degrading activity, and tissue-specific antioxidant effects due to its products CO and biliverdin, this latter being further reduced by biliverdin reductase in bilirubin is an emerging concept. There is a current interest in dietary compounds that can inhibit, retard or reverse the multi-stage pathophysiology of Alzheimer disease, with a chronic inflammatory response, brain injury and beta amyloid associated pathology. Curcumin and ferulic acid, two powerful antioxidants, the first from the curry spice turmeric and the second a major constituent of fruit and vegetables, have emerged as strong inducers of the heat shock response. Food supplementation with curcumin and ferulic acid is considered a nutritional approach to reduce oxidative damage and amyloid pathology in Alzheimer disease. This review summarizes the complex regulation of cellular stress signaling and its relevance to human physiology and disease. PMID- 17274533 TI - Resting energy expenditure and insulin resitance in obese patients, differences in women and men. AB - BACKGROUND AND OBJECTIVE: There is little research about the relation of REE and insulin resistance with gender. The aim of our work was to study gender differences in REE and insulin resistance in obese patients. RESEARCH METHODS AND PROCEDURES: A population of 131 obesity patients was analyzed in a prospective way. The following variables were specifically recorded: age, smoking habit, drinking habit, weight, body mass index (BMI), waist circumference, and waist-hip ratio. Blood pressure, basal glucose, insulin, fibrinogen, and C-reactive protein. HOMA was calculated. An indirect calorimetry, tetrapolar electrical bioimpedance and a serial assessment of nutritional intake with 3 days written food records were performed. RESULTS: The mean age was 31.7 +/- 9.2 years and the mean BMI 34.4 +/- 5.3. Cardiovascular risk factors were similar in both groups. Anthropometric measurements showed an average waist circunference (107.8 +/- 16.1 cm), waist-to hip ratio (0.93 +/- 0.11), and average weight (94.8 +/- 20.2 kg). Bipolar body electrical bioimpedance showed the next data; fat free mass (55.2 +/ 17.1 kg) and fat mass (35.7 +/- 12.3 kg). Indirect calorimetry showed higher resting metabolic rate (REE) in males (2001.7 +/- 443 Kcal/day vs. 1774.7 +/- 344 Kcal/day; p < 0.05). REE corrected by fat free mass was similar (male 34.2 +/- 17 Kcal/day/kg vs female 39 +/- 11.6 Kcal/day/kg; ns). Nutritional intake and HOMA were similar in males and females. In the multivariate analysis with a dependent variable (RMR), the fat free mass remained in the male model (F = 18.5; p < 0.05), with an increase of 17.8 (CI 95%: 9.1-26.2) kcal/day with each 1 kg of fat free mass adjusted by age. In the female model, the fat free mass remained in the model (F = 1 2.5; p < 0.05), with an increase of 15.2 (CI 95%: 6.3-24.2) kcal/day with each 1 kg of fat free mass adjusted by age. CONCLUSION: REE was higher in males than females, with a higher influence of fat free mass in males than females. No association between insulin resistance and REE was detected. PMID- 17274534 TI - Oxidative stress detection: what for? Part I. AB - In this paper we review the diseases, such as cancer, arteriosclerosis, arthritis, neurodegenerative disorders, whose emerging pathogenetic evidence by Free Radicals has been shown either from experimental or from clinical point of view. In the last 10 years the growing evidence of a co-causative responsibility of oxidative stress in some chronic and acute illnesses highlighted the need to improve the diagnostic potential as well as the algorythm of an effective treatment plan. An exhaustive basic description of the Free Radicals action mechanism in different parenchymas to produce damage and clinical symptoms is the very preliminary background to any further investigation as to the specific diseases-oriented diagnostic tests as well as to a rationale therapy. PMID- 17274536 TI - A review of proctological disorders. AB - Ano-perianal lesions are essential part of the family practice setup. Patients usually present with symptoms like pain, bleeding, pruritus, and constipation. In the modern era, the patients prefer a conservative therapy or else they opt for a quick office procedure to get rid of the symptoms. Newer pharmacological therapies and a handful of simple and safe office procedures have emerged in the last decade for treatment of ano-perianal lesions. A judicious application of these techniques has been found successful in tackling most of the proctological ailments. Complicated or advanced pathologies, however, require an expert opinion and it is desirable that such patients are referred to the care of colorectal clinics. This paper describes presentation symptoms, approach towards diagnosis, and various therapeutic modalities of common anal disorders commonly seen in a developing country. PMID- 17274535 TI - The metabolic aspects and hormonal derangements in obstructive sleep apnoea syndrome and the role of CPAP therapy. AB - Obstructive sleep apnea syndrome (OSAS) is part of a metabolic syndrome, whose main aspects are obesity, hypertension and diabetes, already incriminated for cardiovascular events. The evaluation of the effect of OSAS on the hormonal profile of patients shows a number of complex interactions that preclude the exact role of this syndrome among the numerous derangements on hormone levels as well as the effect of continuous positive airway pressure treatment, since many of the changes are known to occur with obesity as well. The clarification of the exact role and the mechanisms underlying these changes will help to stratify the cardiovascular and other health risks of this syndrome as well as the better application of CPAP therapy. PMID- 17274537 TI - Clinical overview of vasculitic syndromes in the pediatric age. AB - Vasculitic syndromes comprise a heterogeneous group of disorders sharing the hystopathologic features of inflammation and necrosis in blood vessels. Their clinical expression depends on site, type and size of the involved vessels and severity of the associated inflammatory symptoms. Classification of vasculitides based on the size of the affected vessels is the most widely used in children. Many different vasculitides with indistinguishable clinical presentation have very different prognosis and treatments. Among the primary systemic non granulomatous vasculitides of medium-sized vessels in pediatrics we have to consider Kawasaki disease and among the small-sized ones Henoch-Schonlein purpura, which is the most frequent vasculitis of the pediatric age and is characterized by vascular deposition of IgA-dominant immune complexes. Accurate diagnosis is the mainstay for the definition of the best therapeutical proposal, though therapies available result largely empirical and based on trials with limited numbers of pediatric patients. PMID- 17274538 TI - Radiodermatitis following kidney cancer radiotherapy. PMID- 17274539 TI - Versatility of cartilage grafts: reimplantation after a second nasal trauma. PMID- 17274540 TI - Association of perceived stress and stiff neck/shoulder with health status: multiple regression models by gender. AB - It is well known that psychological stress affects health status. Stiff neck and shoulder in a broad sense is one of the major somatic complaints among Japanese. The objective was to determine how much perceived stress and stiff neck/shoulder are associated with health-related quality of life (HRQoL) by gender. Participants (n = 512) completed the Japanese version of Perceived Stress Scale, the SF-8 Japanese version and original questions on perceived stiff neck/shoulder. Muscle hardness around the shoulder also was measured with the muscle tension meter. The multiple regression model of the men demonstrated that perceived stress was associated with not only the mental component summary (MCS) (beta: -0.494), but also the physical component summary (PCS) (beta = -0.319) of the SF-8. Although, in the model of the women, perceived stress was also associated with MCS (beta: -0.632) more than in that of the men, stiff neck/shoulder and age group (beta: -0.231; -0.268, respectively), but not stress, were related to PCS. The subjective neck/shoulder stiffness was hardly correlated with the objective shoulder muscle hardness. This study revealed the associations between perceived stress, stiff neck/shoulder and HRQoL, and their difference by gender. The hypothesis of gender differences was discussed with a focus on kind of stressors, perception of stress, admission of negative symptoms and cause of stiff neck/shoulder. PMID- 17274541 TI - Pigment epithelium-derived factor promotes neurite outgrowth of retinal cells. AB - The ability of pigment epithelium-derived factor (PEDF) to promote neurite outgrowth of retinal cells through mitogen-activated protein kinase (MAPK) pathways was examined. Neurite outgrowth effects of PEDF were determined by quantifying the neurite length extending from cultured chick embryo retinal explants, and neurite outgrowth ratio of R28 cells (a neural cell line derived from the neonatal rat retina). MAPK activity levels were determined by inhibition assays. The contribution of signaling pathway was quantified with a specific inhibitor for MAPK: PD98059. PEDF (50 ng/ml) promoted chick retinal neurite elongation and increased the extent of R28 cell neurite outgrowth. PD98059 decreased neurite elongation of chicken retinal explants and the extent of R28 cell neurite outgrowth. PEDF possibly promotes neurite outgrowth for retinal cells by activating MAPK pathways. These data suggest that PEDF provides a useful support for retinal cells through the MAPK pathway and leads to the progress of therapy for many retinal diseases. PMID- 17274542 TI - Nonfunctional pituitary macroadenoma manifested as muscular symptoms. AB - A 75-year-old man with a large pituitary adenoma presented with general muscular weakness, including difficulty in rising in the morning and forceless defecation and urination, and muscular pain, numbness and atrophy in the shoulder, neck and thigh. Testosterone replacement and subsequent resection of the pituitary tumor resulted in resolution of the symptoms. The value of pituitary imaging tests for men with hypogonadotropic hypogonadism is discussed. PMID- 17274543 TI - A gastric fibrolipoma presenting as acute gastrointestinal hemorrhage. AB - A 56-year-old woman was admitted to our hospital with upper gastrointestinal hemorrhage from a gastric submucosal tumor that was treated by a laparoscopic technique. Endoscopy and endoscopic ultrasonography (EUS) revealed a 2-cm submucosal tumor located in the posterior wall of the upper gastric body, showing a heterogeneous hyperechoic tumor. A laparoscopic wedge resection of the stomach was performed. Pathological examinations revealed that the tumor was composed of spindle cells like fibroblasts and mature adipocytes. Immunohistochemical examinations revealed that the tumor was negative for desmin and alpha-smooth muscle actin. Based on these findings, a diagnosis of fibrolipoma was made. EUS is useful for differentiating a fibrolipoma from a gastrointestinal stromal tumor or lipoma by the findings of characteristic echogenesity and detection of the tumor origin. PMID- 17274545 TI - Traditional and computer-based screening and diagnosis of reading disabilities in Greek. AB - In this study, we examined the characteristics of reading disability (RD) in the seventh grade of the Greek educational system and the corresponding diagnostic practice. We presented a clinically administered assessment battery, composed of typically employed tasks, and a fully automated, computer-based assessment battery that evaluates some of the same constructs. In all, 261 children ages 12 to 14 were tested. The results of the traditional assessment indicated that RD concerns primarily slow reading and secondarily poor reading and spelling accuracy. This pattern was matched in the domains most attended to in expert student evaluation. Automatic (computer-based) screening for RD in the target age range matched expert judgment in validity and reliability in the absence of a full clinical evaluation. It is proposed that the educational needs of the middle and high school population in Greece will be best served by concentrating on reading and spelling performance--particularly fluency--employing widespread computer-based screening to partially make up for expert-personnel shortage. PMID- 17274544 TI - Private speech and strategy-use patterns: bidirectional comparisons of children with and without mathematical difficulties in a developmental perspective. AB - The present study examines private speech and strategy-use patterns for solving simple number fact problems in addition. The progressive differentiation by grade between children's levels of private speech internalization--including silence- was investigated and related to children's developmental patterns for subcategories of strategy-use internalization. Comparisons were made between 67 children with math difficulties (MD) and 67 children without MD from Grade 2 to Grade 7 in primary schools. Two separate laboratory investigations were performed for each child to examine private speech and strategy-use internalization. Analysis was based on private speech category differences, strategy-use differences, and differences in the occurrence of private speech-strategy-use combinations. Children without MD showed a grade-determined shift from less to more internalized private speech and from the use of backup strategies to retrieval strategies. In contrast, the private speech and the strategy-use internalization of children with MD, reflected in inaudible private speech and backup strategy use, seemed to converge at earlier developmental levels. The development of children with MD seemed almost to stop at the inaudible private speech-backup strategy combination level. The silence-retrieval strategy combination level was the primary alternative for typical math achievers. In all, the characteristics of the development curves of the children with MD were consistent with a developmental difference and not with a developmental delay model. Implications for intervention and future research methodology are discussed. PMID- 17274546 TI - Intensive instruction affects brain magnetic activity associated with oral word reading in children with persistent reading disabilities. AB - Fifteen children ages 7 to 9 years who had persistent reading difficulties despite adequate instruction were provided with intensive tutorial interventions. The interventions targeted deficient phonological processing and decoding skills for 8 weeks (2 hours per day) followed by an 8-week, 1-hour-per-day intervention that focused on the development of reading fluency skills. Spatiotemporal brain activation profiles were obtained at baseline and after each 8-week intervention program using magnetoencephalography during the performance of an oral sight-word reading task. Changes in brain activity were found in the posterior part of the middle temporal gyrus (Brodmann's Area [BA] 21: increased degree of activity and reduced onset latency), the lateral occipitotemporal region (BA 19/37: decreased onset latency of activation), and the premotor cortex (increased onset latency). Overall changes associated with the intervention were primarily normalizing, as indicated by (a) increased activity in a region that is typically involved in lexical--semantic processing (BA 21) and (b) a shift in the relative timing of regional activity in temporal and frontal cortices to a pattern typically seen in unimpaired readers. These findings extend previous results in demonstrating significant changes in the spatiotemporal profile of activation associated with word reading in response to reading remediation. PMID- 17274547 TI - ADHD and achievement: meta-analysis of the child, adolescent, and adult literatures and a concomitant study with college students. AB - This article presents results from two interrelated studies. The first study conducted a meta-analysis of the published literature since 1990 to determine the magnitude of achievement problems associated with attention-deficit/hyperactivity disorder (ADHD). Effect sizes were significantly different between participants with and without ADHD (sample weighted r = .32, sample weighted d = . 71; p = .001). Effects were also examined according to the moderators of age, gender, achievement domain (reading, math, spelling), measurement method (standardized tests vs. grades, parent/teacher ratings, etc.), sample type (clinical vs. nonclinical), and system used to identify ADHD (DSM-III-R vs. DSM-IV). Significant differences emerged from the moderator comparisons. The second study, using averaged effect sizes from the first study as a baseline for comparison, investigated achievement levels for an understudied age group with ADHD, namely, college students. Unlike previous studies at the college level, the sample incorporated both student and parent ratings (N = 380 dyads). The results were comparable to outcomes from the meta-analysis for college students and adults. Analyses demonstrated modest (R = .21) but meaningful predictive validity across 1 year to end-of-first-year grades. However, unlike earlier studies with children and adolescents, student ratings were as predictive as parent ratings. Findings are discussed in terms of the impact of moderator variables on ADHD and achievement. PMID- 17274548 TI - Toward a resolution of inconsistencies in the phonological deficit theory of reading disorders: phonological reading difficulties are more severe in high-IQ poor readers. AB - This study examined whether high- and low-IQ poor readers differed in patterns of reading performance. Ten-year-old poor readers with IQ scores of 110 and higher showed difficulty in taking a phonological approach to reading, failing to show an advantage in reading high-frequency regular versus irregular words and showing impaired nonword reading accuracy for their reading age. However, poor readers with IQ scores of 90 and below showed a more phonological approach to reading, with better reading of regular than irregular words of both high and low frequency, and with nonword reading skills slower than, but as accurate as, those of reading-age controls. We concluded that the high-IQ poor readers experienced difficulty in taking a phonological approach to reading, whereas the low-IQ poor readers had much less marked phonological problems, supporting Stanovich's phonological-core variable-difference model. PMID- 17274549 TI - Locus and nature of perceptual phonological deficit in Spanish children with reading disabilities. AB - The aims of this study were (a) to determine whether Spanish children with reading disabilities (RD) show a speech perception deficit and (b) to explore the locus and nature of this perceptive deficit. A group of 29 children with RD, 41 chronological age-matched controls, and 27 reading ability-matched younger controls were tested on tasks of speech perception. The effect of linguistic unit (word vs. syllable) and type of phonetic contrast (voicing, place and manner of articulation) were analyzed in terms of the number of errors and the response time. The results revealed a speech perception deficit in Spanish children with RD that was independent of the type of phonetic contrast and of linguistic unit. PMID- 17274550 TI - [Movable geriatric equipment:, an essential link nowadays]. PMID- 17274551 TI - [Eight priorities for the future of hospital public service and medical-social services]. PMID- 17274552 TI - [Explaining treatments to the aged]. PMID- 17274553 TI - [The small agreements of life are not part of confidentiality]. PMID- 17274554 TI - [Preventing alcoholism in the aged]. PMID- 17274555 TI - [Death: announcement and taking charge. Living with death and talking about it]. PMID- 17274557 TI - [Now, at the moment of and after death; which rites need to be performed?]. PMID- 17274556 TI - [Accepting the end of life and death]. PMID- 17274558 TI - [The end of life of an aged parent, a familiar but major upset]. PMID- 17274559 TI - [Certification, an opportunity to ameliorate practical professional connections after death]. PMID- 17274560 TI - [Caring and help in a funeral room at the hospital in Breton ]. PMID- 17274561 TI - [Taking care of the body after death]. PMID- 17274562 TI - [Supporting professional help after a death occurs at home]. PMID- 17274563 TI - [Death at home: what is the psychological life for the neighbors?]. PMID- 17274565 TI - [2/6. The stage III scar]. PMID- 17274564 TI - [Effects of the Leonetti Law in terms of responsibility and confidence]. PMID- 17274566 TI - [Death in an institution]. PMID- 17274567 TI - [Care of the body after death]. PMID- 17274569 TI - Elections were a sign of hope for health care reform. PMID- 17274568 TI - "Honoring the trust" through community benefit. PMID- 17274570 TI - Can the ministry collaborate to form the "next generation" of sponsors? AB - In looking to the future of sponsored ministry of Catholic institutions, the formation of future sponsors--both religious and lay alike--is an important issue. As this ministry continues to evolve, and sponsoring groups determine how best to prepare new sponsors, might it not be time to think about how to pool the ministry's collective wisdom on formation? Sponsors act not only in the name of the health care institution (or other ministry) but on behalf of the faith community engaged in continuing the compassionate healing ministry of Jesus. In Catholic ministry, and particularly health care ministry, sponsors carry out their responsibilities through a multiplicity of organizational relationships. Just as structures differ, so too do criteria that guide who will be called to join a sponsoring group. There are several core elements that are incorporated in the majority of sponsor competency sets. Elements identified by a committee of ministry members, and reviewed by hundreds of sponsors and other ministry leaders are: mission oriented, animated, theologically grounded, collaborative, church related, and accountable. If one is looking at the potential for convening dialogues about possible areas of collaboration in formation, these core elements, with examples of how they are lived out, may offer an outline of areas new sponsors might need to learn more about for their personal and professional development. Our Catholic health ministry depends on leaders who can create and steward organizational cultures that incarnate Jesus' healing. The possibilities for collaboration in the formation of future sponsors are endless, but there are challenges. If you are a member of a sponsor body/council/corporate member in Catholic health care, and are interested in nominating potential persons to take part in a representative group that would discuss possibilities for collaboration in sponsor formation, please go to www.chausa.org/sponsorformation and complete all sections of the nomination form. PMID- 17274571 TI - A collaborative formation program for sponsors. AB - Trends in sponsorship of Catholic health care have opened the door to lay members of the church to become the ministry's canonical stewards. This has led to the call for educational programs to help laity become effective sponsors. The Collaborative Formation Program for Public Juridic Persons--to train potential PJP sponsors--was launched in 2003 by five Catholic health ministries that adopted a PJP model of sponsorship. The program consists of four weekend seminars that are held over an 18-month period. The curriculum is based on an adult education model that combines lecture and selected readings with discussion, personal reflection, ritual, and informal interaction in a reflective setting. Theological and personal competencies are woven into several of the four program sessions. Survey results show that participants see the Collaborative Formation Program as a valuable experience. Their comments indicate that, in addition to formation, the program provides opportunities for networking, brainstorming collaborative actions, mentoring, and accessing a pool of resources. The surveys also revealed that there is some confusion about what participants might expect of themselves once the program has been completed. Their comments suggest that they would like more clarity concerning the program's anticipated effect on them both personally and in their role as potential sponsors. Some questions raised by participants showed a desire for a better understanding of what sponsors might actually do in response to content covered in the formation program. Participants wanted more insight into addressing justice issues, in responding to the poor when health system discretionary funds are limited, and in enacting ethical decision-making processes. The answer to the critical question "How will we know when this transition in roles has been successful?" will emerge as lay colleagues are appointed to sponsorship roles and the effectiveness of that sponsorship is evaluated over time. PMID- 17274572 TI - Pilot program is for potential sponsors. AB - As congregations continue to prepare for the future, they focus particularly on the identification and development of potential new sponsors. The Sisters of Mercy Regional Community of Chicago has launched an initiative to identify persons who might be appropriate for sponsorship ministry. Working with the sisters in the region, we who served on the congregation's leadership team began by looking at changing forms of sponsorship. We sensed that our congregation would need to place laypeople in positions once held by women religious. We saw that we would be placing other-than-sisters not just on leadership teams but in governance as well. In 2005, select board members from the various institutions sponsored by the congregation attended workshops. Following the workshops, we met with the participants to discuss the results and plan next steps. We decided to conduct a brief introduction-to-sponsorship program that would run from January to May 2006. The program, called the "Sponsorship Pilot," would offer such persons a "taste" of what it means to be a sponsor. Those attending could then discern whether this is something they would like to pursue-whether they would like to be contacted and offered an opportunity as positions opened in sponsored works. One important lesson learned from the Sponsorship Pilot has to do with the people invited to participate in it. In our early discussions, we focused on the development of lay sponsors. However, in later feedback from the congregation at large, we were asked why no sisters had been considered to participate. It was a valid point. As for those of who led the Sponsorship Pilot, we admit that our original focus on laity alone was a mistake. We also learned that it is important that the key leaders of the congregation's ministries increase their understanding of sponsorship through experiences such as that provided by Sponsorship Pilot, even if they do not become sponsors. PMID- 17274573 TI - Sponsorship transformation at Ascension Health. AB - Two Catholic health systems, the Daughters of Charity National Health System and the Sisters of St. Joseph Health System, came together to create St. Louis-based Ascension Health in 1999. A third organization, Carondelet Health System, then merged with Ascension Health in December 2002. Ascension Health is sponsored by four provinces of the Daughters of Charity, the Sisters of St. Joseph of Nazareth, and the Sisters of St. Joseph of Carondelet. Ascension Health operates according to a concept it calls "sponsorship of the whole," which has been defined as follows: "The sponsors of Ascension Health exercise canonical responsibility to ensure that the health ministry sustains and strengthens Catholic identity while expressing the charisms of the present and future sponsors. The sponsors act as stewards of Ascension Health's mission and resources, and commit, in partnership with others, to educate, influence, nurture, and develop the combined health ministry to further the healing ministry of Jesus." After several years of serving together on the Sponsors Council-and following much prayer, theological reflection, and in-depth discussion-the sponsors decided to accept the "Sponsorship of the Whole" document. The document challenges sponsors to open their hearts and arms to embrace all of Ascension Health's local health ministries. When Ascension Health was formed in November 1999, it was with the intention of adding laypeople to the Sponsors Council. In late 2005, the system created a work group to explore key areas pertinent to the appointment of lay members to the council. The Sponsors Council then engaged in a rigorous identification and selection process, after which, on July 1, 2006, it welcomed two lay members. Ascension Health will continue to develop its own preferred culture and identity. As the system's metamorphosis unfolds, personal conversion, a new way of relating to others, and changes in both attitudes and values will be necessary. PMID- 17274574 TI - Does Canon Law speak of sponsorship of Catholic works? AB - Though the term "sponsorship" is not used in the Code of Canon Law, it is generally accepted today that "sponsorship" entails the use of a particular name and the exercise of certain responsibilities that arise from this use. A person's good name--whether the "person" is an individual or a group--is of primary importance today; and sponsorship responsibilities are exercised in relation to what the name stands for. In the case of church ministries such as the Catholic health ministry, the term refers to works undertaken in the name of Christ, on behalf of the Catholic Church. Traditionally, sponsorship had emphasized a position of corporate strength and independence through ownership and control via reserved powers. Today, as new relations are established with other providers, a presence is required that relies more on the ability to influence. Sponsorship in canon law entails a relation to the threefold mission and ministry of the church: to teach, to sanctify, and to serve God's people. Undoubtedly, health care fits in among these elements of ecclesial service. It has generally been held that for a work to be identified as "Catholic," it must, in one way or another, be related to a juridic person in the church, such as a diocese, a religious institute, one of the institute's provinces, or even one of its established houses (canon 634). There could also be situations in which no formal juridical person is involved and yet the work is considered to be "Catholic." Lately, new entities established specifically for sponsorship purposes have been recognized either by bishops or by the Holy See. These entities, usually known as "public juridic persons" (but sometimes also called "foundations") assume the sponsorship responsibilities previously assumed by a religious institute (or one of its parts) or a diocese. In some instances, these entities also assume all the ownership and property rights previously held by the original institute or diocese. PMID- 17274575 TI - Catholic Health Initiatives at 10. AB - The summer of 2006 marked the 10th anniversary of the formation of Denver-based Catholic Health Initiatives (CHI). Formed in 1996 as the result of the merger of three Catholic health care systems, and soon joined by a fourth, the system integrated a diverse collection of health care facilities previously sponsored by 12 different religious congregations. It was the first Catholic health system to give laity a sponsorship role in its facilities. CHI's facilities are sponsored by a public juridic person (PJP), the Catholic Health Care Federation (CHCF). The same people who sit on the system's board also constitute CHCF. They are thus responsible for both governance and sponsorship. CHI was the first Catholic health care system to give laypersons a sponsorship role in its facilities. Establishing the PJP was a long and complex task. Eventually, the church determined that CHI's PJP should be pontifical, accountable to the Congregation for Institutes of Consecrated Life and Societies of Apostolic Life in Rome. CHCF in 1991 became the first PJP in health care in the United States. CHI's staff, led by its first president and chief executive officer, Patricia Cahill, quickly took steps to help the new system begin to coalesce, establishing a single, systemwide pension plan, debt policy, and so forth. Also challenging was the creation of a systemwide new culture. An essential step in the development of CHI's culture was the involvement of employees in the identification of its core values: reverence, integrity, compassion, and excellence, The creation of CHI's Mission and Ministry Fund also helped give the system an identity. This fund provides grants to programs that take an innovative approach to building healthy communities, a goal expressed in CHI's mission and vision statements. The people who created CHI and nurtured it during its first decade give it high marks for faithful adherence to its mission. Even so, they acknowledge that there is always more work to be done. PMID- 17274576 TI - "Diversity is at the core of who we are". AB - In an effort to become a more fully diverse organization, St. Louis-based SSM Health Care (SSMHC) implemented a plan called "Strategic Goals for Diversity for 1998 to 2004." The plan called for Increasing diversity among SSMHC employees. Improving support to, and alliances with, organizations that pursue fairness and equality for all people. Establishing a work environment that rewards and recognizes excellence and attracts and retains the best people, regardless of factors like race, religion, disability, and gender. Increasing business partnerships with minority and women suppliers. Having established strategic goals, SSM launched a Diversity Forum: a corporate-sponsored gathering designed to develop the careers of people of color, of different ethnic backgrounds, or with disabilities. Diversity Forum participants suggested that mentoring minority employees would help SSM reach its goals. In 2000, the system launched its Diversity Mentoring Program, designed to last four years. The program had two main purposes: To increase the number of people of color, of different ethnicity, or with disabilities in the system's professional and managerial ranks. To prepare these minority professionals and managers for upward mobility by pairing them with executive leaders. Along with the focus on SSM's employees, the system looked outside as well, to its relationships with local communities. The organization worked toward expanding its commitment to purchase from local, small, and minority-owned businesses. In 2005, to help SSM entities meet new goals for 2005-2010 (with a new emphasis on minority patients and customers), the system introduced a new measurement tool, the Diversity Scorecard, which is a comprehensive measuring tool that allows SSM leaders to benchmark their efforts. PMID- 17274577 TI - Who really wants health care justice? AB - U.S. health care is at a crossroads. It faces many challenges--the most evident being unsustainable cost increases and diminishing access. For decades, attempts at reform have been unsuccessful. One reason our traditional approaches have not worked is that we who serve the ministry have not brought to those efforts sufficient reflection concerning the deeper, values-level attitudes concerning reform. Instead, the reform movement has concentrated on promoting particular policy solutions. Ultimately, of course, we must agree on a delivery and financing system if we are to redress the situation. But first we must recognize that U.S. health care's fundamental challenge is moral and social in nature. Stakeholders will not let go of the status quo until a critical mass of people becomes convinced that there is a serious moral and social imperative to do so. Social change of this magnitude is not simply a matter of comprehensive new policy. To be effective, it must be accompanied by sustained individual and public conscience work that grounds a significant social movement comprising a critical mass of each of those stakeholders. Several principles from the Catholic tradition--the common good, solidarity, and stewardship--are particularly relevant to the individual and public conscience work necessary in the health care reform movement. Health care professionals and organizations are simultaneously part of the solution and part of the problem. By keeping this interior dialogue alive, in ourselves and in our work communities, we are much more likely to get at the root causes of our unjust health system and to contribute to the larger social movement that brings about more health care justice. This article contains a "conscience work exercise" that will help individuals and organizations examine and identify the values, attitudes, and dispositions that contribute to health care justice and those that keep us mired in the status quo. PMID- 17274578 TI - Parish nursing and hospitals. AB - Parish nursing is an emerging area of specialized professional nursing practice that focuses on health maintenance and health promotion for parishioners and the community. Health care occurs across a continuum along which hospitals provide a key function. There is a role for hospitals in relation to parish nursing and faith-based health care organizations have a greater obligation than secular ones to partner with parish nursing programs. Faith-based health care facilities, like secular ones, are institutions that bring health care professionals together to apply their knowledge, judgment, and skills to provide care for those in need of such services. But faith-based facilities differ from others in sharing a holistic perspective of health intended to benefit the individual and society, particularly those who are marginalized. This obligation to serve enables God's work because caring for those in need is essential for a just and beneficent society. It seems reasonable to assume that partnering with parish nurse programs is a fitting role for faith-based hospitals. In such circumstances, the facility may choose to introduce the parish nurse concept to the community by hosting a town hall meeting or a workshop with community partners. The facility may also fund parish nursing exhibitions at community events and conferences. The notion of "partnering with," although it carries no theological implications, is in the health care context somewhat akin to the Catholic notion of "sponsorship." The church's sponsorship of health care facilities should be seen as a ministry in itself, and such an approach would "shift the focus from preservation to enhancement, from being a guardian to being a creator, from a sense of diminishment to one of empowerment." Faith-based health care organizations have a responsibility to focus on holistic health for both the individual and society at large, particularly the health of people who are marginalized. It is not only logical that faith-based health care organizations should partner with parish nursing programs--it is imperative that they do so. PMID- 17274580 TI - Hitting the ground running. AHA's new president shares ideas about improving health care. PMID- 17274579 TI - Relieving pain in the elderly. AB - In 2000, people aged 65 and older made up 12.4 percent of the U.S. population. Between now and 2011, when the earliest-born of the baby-boom generation reaches that age, the nation will see a rapid growth in its senior citizen population. It has been estimated that pain occurs in from 45 percent to 85 percent of the geriatric population. Much of it is undertreated. Undertreated pain leads to other problems, including reduced quality of life, decreased socialization, depression, sleep disturbances, cognitive impairment, and malnutrition. For a population already vulnerable because of aging, the costs incurred by more frequent physician visits and hospitalizations can be financially devastating. Health professionals have a moral imperative to help elderly people in pain. The management of pain in geriatric patients can be complicated by the changing physiology that occurs with aging. Older people are also more likely to be living with multiple chronic diseases, necessitating many daily medications, thereby increasing the risk of negative drug-disease and drug-drug interactions. Older patients often show atypical presentations of pain. Depression can also play a role in the assessment and treatment of pain. For a number of reasons, many older people choose not to report their pain. Often they are afraid that they will be involuntarily hospitalized or subjected to invasive procedures if they report pain. Another important barrier to successful pain management is the fact that older people are often misinformed about the aging process, analgesics, pain management, and opioid addiction. Recognition of the problem of undertreatment of pain in older persons prompts the following question: What can be done to solve the problem? Educational in-service sessions improve the quality of patient care, because they improve providers' pain-management skills and attitudes. Patient education is also extremely important. When combined with teaching about self management and coping strategies, it can improve the patient's pain management. PMID- 17274581 TI - Improving patient safety in perinatal services. PMID- 17274582 TI - Direct 3D imaging of the knee menisci during 16-row multislice CT arthrography. AB - The aim of this paper was to explore the possibility to obtain high quality 3D images of the knee menisci during 16-row multidetector (MDCT) CT arthrography and to illustrate the performances of 3D images versus classical multi-axial 2D reformatted views through the study of a continuous series of 322 unselected patients. Correct to excellent meniscal 3D images were technically available in 97.7% of cases. When compared with 2D reformatted views, the negative predictive value, positive predictive value, sensitivity and specificity of 3D meniscal images were respectively 98.9, 98.6, 98.6 and 98.9% for the medial meniscus (MM) and 100% for the lateral meniscus (LM). Available in most patients, convincing 3D images of knee menisci obtained during 16-row MDCT arthrography could probably become a new method of choice for optimal illustration of complex meniscal tears in the future. Alternatively, efforts should be done to promote the development of similar 3D imaging of the knee menisci during MR studies that are considered by many authors as the gold standard non-invasive imaging method of the knee. PMID- 17274583 TI - Additional value of CT-fluoroscopic biopsy of pulmonary lesions: a retrospective study of 69 patients. AB - The purpose of this retrospective study was to evaluate the diagnostic accuracy of CT-fluoroscopic transthoracic biopsy of pulmonary lesions related to their localization and size. The complication rate was also evaluated. Between January 2003 and June 2004, we performed seventy-two CT-fluoroscopic transthoracic biopsies in sixty-nine patients. Lesions were subdivided in subpleural, peripheral and central lesions. The lesions were also subdivided concerning their diameter. Fifty three lesions (77%) had a final diagnosis of malignancy and 13 lesions (19%) had a final benign diagnosis. CT-fluoroscopic transthoracic biopsy had an overall diagnostic accuracy of 84.4%, sensitivity of 80.7%, specificity of 100%, positive predictive value of 100% and negative predictive value of 54.5%. For lesions between 1 and 3 cm the accuracy was 78.5% for lesions greater than 3 cm 87%. Only one lesion was smaller than 1 cm, this lesion was true positive. There were no false-positive findings. Pneumothoraces were observed in only 7 patients (10%) and there was only 1 small postpuncture hemothorax (1.7%). CT fluoroscopic biopsy of pulmonary lesions has a good diagnostic accuracy with a very low complication rate. The accuracy is higher for larger lesions, but there is no significant difference for subpleural and peripheral lesions. PMID- 17274584 TI - MR diagnosis of transdural disc herniation causing cauda equine syndrome. AB - Intradural disc herniation is very rare. We describe a case of anterior transdural L4-L5 disc herniation presenting as a partial cauda equina syndrome without related back pain or history of back pain. MRI allowed presurgical diagnosis showing an irregular intradural mass that did not enhance. That lack of enhancement could be related to the fact that the disc herniation was relatively recent. PMID- 17274585 TI - Duodenal stromaltumor detected by CT-enteroclysis. AB - Gastro-intestinal stromal tumors can present with gastro-intestinal hemorrhage, often with an acute episode of abdominal pain, weight loss, nausea and vomiting. We present a case of a young man who presented with gastrointestinal bleeding. The patient previously presented with gastro-intestinal bleeding but several investigations like gastroscopy, coloscopy, Ectopic gastric mucosa-scan, and computed tomography were reported as negative. A well-circumscribed submucosal tumoral mass in the duodenum with maximal thickness of 15 mm was however detected by CT-enteroclysis. Microscopic examination confirmed the presence of a gastro intestinal stromal tumor. PMID- 17274586 TI - Pleurosubcutaneous fistula presenting as lateral thoracic lump in an oncologic patient. AB - We describe a case of pleurosubcutaneous fistula of the left thoracic wall in an oncologic female patient. She presented with left-sided pain and a chest wall mass bulge suspicious for breast neoplasm metastasis. PMID- 17274587 TI - Imaging findings in paraspinal extra osseous Ewing sarcoma. AB - We present a case of extraskeletal Ewing sarcoma (ES) in a 32-year-old male patient. The patient reported a painful mass in the thoracic paraspinal area which reached a considerable size in a one-month interval. Sonography and CT showed a heterogeneous, hypoechoic/hypodense soft tissue mass embedded in the dorsal paraspinal musculature. MRI with contrast enhancement showed a solid tumor surrounding areas of necrosis/cystic degeneration. Despite wide contact with the spine and ribs there was no intrathoracic/intraspinal extension or neural foraminal invasion. The imaging findings are non specific; a paravertebral location in the appropriate age group may be the clue to the diagnosis of extraskeletal ES. PMID- 17274588 TI - Amyloid deposition of the breast in primary Sjogren syndrome. AB - We report amyloid deposition in the breast presenting as suspicious microcalcifications on screening mammography. Stereotactic mammotome biopsy provided the diagnosis. The history of the patient revealed primary Sjogren syndrome. The combination of amyloid deposition in the breast and Sjogren's syndrome has only rarely been reported. PMID- 17274590 TI - Radiology of Gaucher disease (type 1) and bone manifestations: the Dutch experience. AB - Evaluating bone disease in Gaucher disease is a very important part of monitoring patients on therapy. In the Academic Medical Center (AMC) there is ample experience covering the evaluating of bone marrow involvement. Both state of the art Quantitative Chemical Shift Imaging (QCSI) as well as alternatives have been subject of research protocols. Our experiences are described. PMID- 17274589 TI - Bilateral putaminal necrosis due to methanol abuse. AB - Symmetrical lesions in the basal ganglia are accepted as the characteristic radiological feature of methanol toxicity. A case of chronic deliberate repeated methanol ingestion is presented. The typical MRI findings of basal ganglia lesions on T1 and T2 weighted images, FLAIR, diffusion and T1-weighted post Gadolinium images are presented. To our knowledge, this is the first case in which late diffusion and post contrast MRI images, showing necrotic sequelae due to methanol ingestion, are reported. PMID- 17274591 TI - Guidelines for Belgian MR centers for monitoring of bone marrow involvement in patients with Gaucher disease. AB - The purpose of this short manuscript is to describe imaging guidelines for quantification of bone marrow involvement in Gaucher disease. PMID- 17274593 TI - Bilateral gynecomastia with microcalcifications in an HIV infected hemophilia A patient after HAART. PMID- 17274592 TI - Value of magnetic resonance imaging in early assessment of proximal femoral focal deficiency (PFFD). AB - Proximal femoral focal deficiency (PFFD) is a developmental defect of the proximal femur and acetabulum. PFFD includes a spectrum of findings ranging from mild femoral shortening with varus deformity to complete absence of both the acetabulum and the proximal femur. Most attempts to classify the severity of the abnormality are based on the radiographic findings. The most commonly used system is that of Aitken. This classification scheme is based upon the presence and location of the femoral head and neck on conventional radiography and provides an assessment of future limb function and plan treatment. Since this scheme however relies on conventional radiography for classification, it is difficult to classify a child until skeletal maturity which is often delayed in children with PFFD. Nevertheless, the earlier patients can be treated, the earlier normal growth can start. This case report illustrates the value of Magnetic Resonance Imaging (MRI) in addition to the standard radiographs, for early and more accurate assessment of the articular cartilaginous anatomy and soft tissue prior to ossification of the femoral capital epiphysis. As a consequence, the patient could be treated earlier to benefit treatment outcome. PMID- 17274594 TI - Small bowel obstruction by apricot pit in Crohn's disease. PMID- 17274595 TI - News from the universities. Doctoral thesis: percutaneous vertebroplasty in osteoporotic vertebral compression fractures. PMID- 17274596 TI - Phosphorylation and processing of the quorum-sensing molecule autoinducer-2 in enteric bacteria. AB - Quorum sensing is a process of chemical communication that bacteria use to assess cell population density and synchronize behavior on a community-wide scale. Communication is mediated by signal molecules called autoinducers. The LuxS autoinducer synthase produces 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor to a set of interconverting molecules that are generically called autoinducer-2 (AI-2). In enteric bacteria, AI-2 production induces the assembly of a transport apparatus (called the LuxS regulated (Lsr) transporter) that internalizes endogenously produced AI-2 as well as AI-2 produced by other bacterial species. AI-2 internalization is proposed to be a mechanism enteric bacteria employ to interfere with the signaling capabilities of neighboring species of bacteria. We have previously shown that Salmonella enterica serovar Typhimurium binds a specific cyclic derivative of DPD. Here we show that following internalization, the kinase LsrK phosphorylates carbon-5 of the open form of DPD. Phosphorylated DPD (P-DPD) binds specifically to the repressor of the lsr operon, LsrR, consistent with P-DPD being the inducer of the lsr operon. Subsequently, LsrG catalyzes the cleavage of P-DPD producing 2-phosphoglycolic acid. This series of chemical events is proposed to enable enteric bacteria to respond to the presence of competitor bacteria by sequestering and destroying AI-2, thereby eliminating the competitors' intercellular communication capabilities. PMID- 17274597 TI - Side-chain losses in electron capture dissociation to improve peptide identification. AB - Analysis of a database of some 20 000 conventional electron-capture dissociation (ECD) mass spectra of doubly charged ions belonging to tryptic peptides revealed widespread appearance of w ions and related u ions that are due to partial side chain losses from radical z* ions. Half of all z* ions that begin with Leu or Ile produce w ions in conventional one-scan ECD mass spectra, which differentiates these isomeric residues with >97% reliability. Other residues exhibiting equally frequent side chain losses are Gln, Glu, Asp, and Met (cysteine was not included in this work). Unexpectedly, Asp lost not a radical group like other amino acids but a molecule CO2, thus giving rise to a radical w* ion with the possibility of a radical cascade. Losses from amino acids as distant as seven residues away from the cleavage site were detected. The mechanism of such losses seems to be related to radical migration from the original site at the alphaCn atom in a zn* ion to other alphaC and betaC atoms. The side chain losses confirm sequence assignment, improve the database matching score, and can be useful in de novo sequencing. PMID- 17274598 TI - Solution structure of human Brg1 bromodomain and its specific binding to acetylated histone tails. AB - Human brahma-related gene 1 (Brg1) is a core protein in human SWI/SNF chromatin remodeling complex which regulates gene expression. Brg1 contains a bromodomain that has been shown to anchor the entire complex to promoter nucleosomes by interacting with histones that are acetylated at specific lysine residues. The Brg1 bromodomain belongs to an important subclass of the bromodomain family for which no structural information is known. Here we report the solution structure of the Brg1 bromodomain determined by NMR. The Brg1 bromodomain conserves the left-handed, four-helix bundle topology found in other bromodomain structures. However, the alphaZ helix of Brg1 bromodomain is about 4 residues shorter relative to previously published bromodomain structures. Using NMR perturbation studies, we demonstrate the Brg1 bromodomain binds acetyllysine in the context of histone tails, with no comparable affinity for unacetylated peptides. The estimated dissociation constants (KD) for acetylated histone peptides H4-AcK8 and H4-AcK12 are 4.0 and 3.6 mM, respectively. In this study the dominant substrate was H3-AcK14 (KD approximately 1.2 mM). Mutagenesis analysis reveals several residues important for the binding specificity. Using molecular dynamics simulations, we present a model of the Brg1 bromodomain in complex with H3-AcK14 and discuss the potential interactions which provide the selectivity of the Brg1 bromodomain for histone H3-AcK14. PMID- 17274599 TI - Investigating the "steric gate" of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase by targeted insertion of unnatural amino acids. AB - To investigate how structural changes in the amino acid side chain affect nucleotide substrate selection in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), a variety of non-natural tyrosine analogues were substituted for Tyr115 of p66 RT. RT variants containing meta-Tyr, nor-Tyr, aminomethyl-Phe, and 1- and 2-naphthyl-Tyr were produced in an Escherichia coli coupled transcription/translation system. Mutant p66 subunits were reconstituted with wild-type (WT) p51 RT and purified by affinity chromatography. Each modified enzyme retained DNA polymerase activity following this procedure. Aminomethyl Phe115 RT incorporated dCTP more efficiently than the WT and was resistant to the chain terminator (-)-beta-2',3'-dideoxy-3'-thiacytidine triphosphate (3TCTP) when examined in a steady-state fidelity assay. However, 2-naphthyl-Tyr115 RT inefficiently incorporated dCTP at low concentrations and was kinetically slower with all dCTP analogues tested. Models of RT containing these side chains suggest that the aminomethyl-Phe115 substitution provides new hydrogen bonds through the minor groove to the incoming dNTP and the template residue of the terminal base pair. These hydrogen bonds likely contribute to the increased efficiency of dCTP incorporation. In contrast, models of HIV-1 RT containing 2-naphthyl-Tyr115 reveal significant steric clashes with Pro157 of the p66 palm subdomain, necessitating rearrangement of the active site. PMID- 17274600 TI - Evidence that the principal CoII-binding site in human serum albumin is not at the N-terminus: implication on the albumin cobalt binding test for detecting myocardial ischemia. AB - Human serum albumin (HSA) is the most abundant protein in the blood plasma and is involved in the transport of metal ions. Four metal-binding sites with different specificities have been described in HSA: (i) the N-terminal site provided by Asp1, Ala2, and His3, (ii) the site at the reduced Cys34, (iii) site A, including His67 as a ligand, and (iv) the nonlocalized site B. HSA can bind CoII, and HSA was proposed to be involved in CoII transport. Recently, binding of CoII to HSA has attracted much interest due to the so-called albumin cobalt binding (ACB) test approved by the Food and Drug Administration for evaluation of myocardial ischemia. Although the binding of CoII to HSA is important, the binding of CoII to HSA is not well-characterized. Here the binding of CoII to HSA was studied under anaerobic conditions to prevent CoII oxidation. Electronic absorption, EPR, and NMR spectroscopies indicate three specific and well-separated binding sites for CoII in HSA. CoII ions in all three sites are in a high-spin state and coordinated in a distorted octahedral geometry. Competition experiments with CdII (known to bind to sites A and B) and CuII (known to bind to the N-terminal site) were used to identify the sites of binding of CoII to HSA. They revealed that the first two equivalents of CoII bind to sites A and B. Only the third may be bound to the N-terminal site. The repercussions of these results on the understanding of the ACB test and hence the myocardial ischemia are discussed. PMID- 17274601 TI - Single amino acid substitutions in puroindoline-b mutants influence lipid binding properties. AB - External reflectance Fourier transform infrared (ER-FTIR) spectroscopy and surface pressure measurements have been used to characterize the interaction of wild-type puroindoline-b (Pin-b) and two mutant forms featuring single residue substitutions-namely, Gly-46 to Ser-46 (Pin-bH) and Trp-44 to Arg-44 (Pin-bS) with condensed-phase monolayers of zwitterionic (L-alpha dipalmitoylphosphatidylcholine, DPPC) and anionic (L-alpha dipalmitoylphosphatidyl-dl-glycerol, DPPG) phospholipids. The interaction with anionic DPPG monolayers, monitored by surface pressure isotherms, was influenced significantly by mutations in Pin-b (p < 0.05); wild-type Pin-b showed the highest surface pressure change of 10.6 +/- 1.0 mN m-1, followed by Pin-bH (7.9 +/- 1.6 mN m-1) and Pin-bS (6.3 +/- 1.0 mN m-1), and the surface pressure isotherm kinetics were also different in each case. Integrated Amide I peak areas from corresponding ER-FTIR spectra confirmed the differences in adsorption kinetics, but also showed that differences in adsorbed amount were less significant, suggesting that mutations influence the degree of penetration into DPPG films. All Pin-b types showed evidence of interaction with DPPC films, detected as changes in surface pressure (5.6 +/- 1.1 mN m-1); however, no protein peaks were detected in the ER-FTIR spectra, which indicated that the interaction was via penetration with limited adsorption at the lipid/water interface. The expression of Pin-b mutants is linked to wheat endosperm hardness; therefore, the data presented here suggest that the lipid binding properties may be pivotal within the mechanism for this quality trait. In addition, the data suggest antimicrobial activities of Pin-b mutants would be lower than those of the wild type Pin-b, because of decreased selectivity toward anionic phospholipids. PMID- 17274603 TI - Electron transfer reactions of peroxydisulfate and fluoroxysulfate reactions with the cyanide complexes M(CN)n4- (M=Fe(II), Ru(II), Os(II), Mo(IV), and W(IV)). AB - The stoichiometry and the kinetics of oxidation of the cyanide complexes M(CN)n4- (M = Fe(II), Ru(II), Os(II), Mo(IV), and W(IV)) by the peroxydisulfate ion, S2O8(2-), and by the much more strongly oxidizing fluoroxysulfate ion, SO4F-, were studied in aqueous solutions containing Li+. Reactions of S2O8(2-) with M(CN)n4- are known to be strongly catalyzed by Li+ and other alkali metal ions, and this applies also to the corresponding reactions of SO4F-. The primary reactions of S2O8(2-) and SO4F- have both been found to be one-electron processes in which the equally strong O-O and O-F bonds are broken. The primary reaction of S2O8(2-) consists of a single step yielding M(CN)n3-, SO4-, and SO42-, whereas the primary reaction of SO4F- comprises two parallel one-electron steps, one leading to M(CN)n3-, SO4-, and F- and the other yielding M(CN)n-1(2-), CN-, SO4- and F-. The relationship between the rate constants and the standard free energies of reaction for the Li+-catalyzed reactions of SO4F- and S2O8(2-) with M(CN)n(4-), and for the uncatalyzed reactions of S2O8(2-) with bipyridyl and phenanthroline complexes MLn2+ (M = Fe(II), Ru(II), and Os(II)) studied previously, suggests that the intrinsic barrier for all three sets of reactions is similar, i.e., unaffected by the Li+ catalysis, and that the electron transfer and the breakage of the O-O and O-F bonds are concerted processes. PMID- 17274602 TI - Structural basis for binding of porphyrin to human telomeres. AB - Maintenance of telomere integrity is a hallmark of human cancer, and the single stranded 3' ends of telomeric DNA are targets for small-molecule anticancer therapies. We report here the crystal structure of a bimolecular human telomeric quadruplex, of the sequence d(TAGGGTTAGGG), in a complex with the quadruplex binding ligand 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) to a resolution of 2.09 A. The DNA quadruplex topology is parallel-stranded with external double-chain-reversal propeller loops, consistent with previous structural determinations. The porphyrin molecules bind by stacking onto the TTA nucleotides, either as part of the external loop structure or at the 5' region of the stacked quadruplex. This involves stacked on hydrogen-bonded base pairs, formed from those nucleotides not involved in the formation of G-tetrads, and there are thus no direct ligand interactions with G-tetrads. This is in accord with the relative nonselectivity by TMPyP4 for quadruplex DNAs compared to duplex DNA. Porphyrin binding is achieved by remodeling of loops compared to the ligand free structures. Implications for the design of quadruplex-binding ligands are discussed, together with a model for the formation of anaphase bridges, which are observed following cellular treatment with TMPyP4. PMID- 17274604 TI - Theoretical study of the pyrolysis of methyltrichlorosilane in the gas phase. 1. Thermodynamics. AB - Structures and energies of the gas-phase species produced during and after the various unimolecular decomposition reactions of methyltrichlorosilane (MTS) with the presence of H2 carrier gas were determined using second-order perturbation theory (MP2). Single point energies were obtained using singles + doubles coupled cluster theory, augmented by perturbative triples, CCSD(T). Partition functions were obtained using the harmonic oscillator-rigid rotor approximation. A 114 reaction mechanism is proposed to account for the gas-phase chemistry of MTS decompositions. Reaction enthalpies, entropies, and Gibbs free energies for these reactions were obtained at 11 temperatures ranging from 0 to 2000 K including room temperature and typical chemical vapor deposition (CVD) temperatures. Calculated and experimental thermodynamic properties such as heat capacities and entropies of various species and reaction enthalpies are compared, and theory is found to provide good agreement with experiment. PMID- 17274605 TI - Theoretical study of the pyrolysis of methyltrichlorosilane in the gas phase. 2. Reaction paths and transition states. AB - The kinetics for the previously proposed 114-reaction mechanism for the chemical vapor deposition (CVD) process that leads from methyltrichlorosilane (MTS) to silicon carbide (SiC) are examined. Among the 114 reactions, 41 are predicted to proceed with no intervening barrier. For the remaining 73 reactions, transition states and their corresponding barrier heights have been explored using second order perturbation theory (MP2) with the aug-cc-pVDZ basis set. Final energies for the reaction barriers were obtained using both MP2 with the aug-cc-pVTZ basis set and coupled cluster theory (CCSD(T)) with the aug-cc-pVDZ basis set. CCSD(T)/aug-cc-pVTZ energies were estimated by assuming additivity of basis set and correlation effects. Partition functions for the computation of thermodynamic properties of the transition states were calculated with MP2/aug-cc-pVDZ. Forward and reverse Gibbs free energy barriers were obtained at 11 temperatures ranging from 0 to 2000 K. Important reaction pathways are illustrated at 0 and 1400 K. PMID- 17274606 TI - Interaction of low-energy ions and atoms of light elements with a fluorinated carbon molecular lattice. AB - The mechanism of interaction of low-energy atoms and ions of light elements (H, H+, He, Li, the kinetic energy of the particles 2-40 eV) with C6H6, C6F12, C60, and C60F48 molecules was studied by ab initio MD simulations and quantum-chemical calculations. It was shown that starting from 6 A from the carbon skeleton for the "C6H6 + proton" and "C60 + proton" systems, the electronic charge transfer from the aromatic molecule to H+ occurs with a probability close to 1. The process transforms the H+ to a hydrogen atom and the neutral C6H6 and C60 molecules to cation radicals. The mechanism of interaction of low-energy protons with C6F12 and C60F48 molecules has a substantially different character and can be considered qualitatively as the interaction between a neutral molecule and a point charge. The Coulomb perturbation of the system arising from the interaction of the uncompensated proton charge with the Mulliken charges of fluorine atoms results in an inversion of the energies of the electronic states localized on the proton and on the C6F12 and C60F48 molecules and makes the electronic charge transfer energetically unfavorable. On the different levels of theory, the barriers of the proton penetration for the C6F12 and C60F48 molecules are from two to four times lower than those for the corresponding parent systems (C6H6 and C60). The penetration barriers of the He atom and Li+ ion depend mainly on the effective radii of the bombarding particles. The theoretical penetration and escaped barriers for the "Li+ + C60" process qualitatively explain the experimental conditions of synthesis of the Li@C60 complex. PMID- 17274607 TI - Topological characterization of HXO2 (X = Cl, Br, I) isomerization. AB - The isomerization reactions of HOOX --> HOXO --> HXO2 (X = Cl, Br, I) have been studied by using the density functional theory. The breakage and formation of the chemical bonds of the titled reactions have been discussed by the topological analysis method of electronic density. The calculated results show that there is a transitional structure of a three-membered ring on each of the isomerization reaction paths. The "energy transition state (ETS)" and the "structure transition state (STS)" in all of the studied reactions have been found. In all these reactions, the position of the structure transition state and the scope of the structure transition region correlate well with the reaction energy. The STS appears after the ETS in the exothermic reaction but it appears before the ETS in the endothermic reaction. The less reaction energy there is, the wider scope of the structure transition region. PMID- 17274608 TI - The guanine tautomer puzzle: quantum chemical investigation of ground and excited states. AB - Combined density functional and multireference configuration interaction methods have been employed to explore the ground and low-lying electronically excited states of the most important tautomeric and rotameric forms of guanine with the purpose of resolving the conflicting assignments of IR-UV bands found in the literature. The calculations predict sharp 1(pi-->pi*) origin transitions for the RN1 rotamer of the 7H-amino-hydroxy species and the RN7 rotamer of the 9H-amino hydroxy species. The other 9H-amino-hydroxy rotamer, RN1, undergoes ultrafast nonradiative decay and is thus missing in the UV spectra. Because of its very small Franck-Condon factor and the presence of a conical intersection close by, it appears questionable, whether the 1(pi-->pi*) origin transition of 9H-amino oxo-guanine can be observed experimentally. Vibrational overlap is more favorable for the 1(pi-->pi*) origin transition of the 7H- amino-oxo form, but also this tautomer is predicted to undergo ultrafast nonradiative decay of the 1(pi-->pi*) population. The good agreement of calculated IR frequencies of the amino-oxo species with recent IR spectra in He droplets and their mismatch with peaks observed in IR-UV spectra indicate that none of the bands stem from 7H- or 9H amino-oxo guanine. Instead, our results suggest that these bands originate from 7H-imino-oxo guanine tautomers. In the excited-state dynamics of the biologically relevant 9H-amino-oxo tautomer, a diffuse charge transfer state is predicted to play a significant role. PMID- 17274609 TI - Atropisomeric 3-(beta-hydroxyethyl)-4-arylquinolin-2-ones as Maxi-K potassium channel openers. AB - The synthesis of a series of 3-beta-hydroxyethyl-4-arylquinolin-2-ones is described. These compounds contain hydrophilic and hydrophobic substituents ortho to the phenolic OH in the C ring of the quinolinone. Electrophysiological evaluation of the panel of compounds revealed that 11 and 16 with an unbranched ortho substituent retain activity as maxi-K ion channel openers. Members of this series of compounds can exist as stable atropisomers. Calculated estimates of the energy barrier for rotation around the aryl-aryl single bond in 3 is 31 kcal/mol. The atropisomers of (+/-)-3, (+/-)-4, and (+/-)-11 were separated by chiral HPLC and tested for their effect on maxi-K mediated outward current in hSlo injected X. laevis oocytes. The (-) isomer in each case was found to be more active than the corresponding (+) isomer, suggesting that the ion channel exhibits stereoselective activation. X-ray crystallographic structures of (+)-3 and (+)-11 were determined. Evaluation of the stability of (-)-3 at 80 degrees C in n butanol indicated a 19.6% conversion to (+)-3 over 72 h. In human serum at 37 degrees C (-)-3 did not racemize over the course of the 30 h study. PMID- 17274610 TI - Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure activity relationship, and in vivo efficacy. AB - Compounds that simultaneously activate the three peroxisome proliferator activated receptor (PPAR) subtypes alpha, gamma, and delta hold potential to address the adverse metabolic and cardiovascular conditions associated with diabetes and the metabolic syndrome. We recently identified the indanylacetic acid moiety as a well-tunable PPAR agonist head group. Here we report the synthesis and structure-activity relationship (SAR) studies of novel aryl tail group derivatives that led to a new class of potent PPAR pan agonists. While most of the tail group modifications imparted potent PPAR delta agonist activity, improvement of PPAR alpha and gamma activity required the introduction of new heterocyclic substituents that were not known in the PPAR literature. Systematic optimization led to the discovery of 4-thiazolyl-phenyl derivatives with potent PPAR alpha/gamma/delta pan agonistic activity. The lead candidate from this series was found to exhibit excellent ADME properties and superior therapeutic potential compared to known PPAR gamma activating agents by favorably modulating lipid levels in hApoA1 mice and hyperlipidemic hamsters, while normalizing glucose levels in diabetic rodent models. PMID- 17274611 TI - Structure-based pharmacophore identification of new chemical scaffolds as non nucleoside reverse transcriptase inhibitors. AB - A structure-based molecular modeling approach was performed to identify novel structural characteristics and scaffolds that might represent new classes of HIV 1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). The software LigandScout was used for identification and visualization of protein-ligand interaction sites and pharmacophore model generation. In the next step virtual screening of 3D multiconformational databases together with docking experiments allowed the identification of promising candidates for biological testing. The positive biological results obtained confirm the validity of our work strategy. PMID- 17274612 TI - A series of new organic-inorganic molybdenum arsenate complexes based on [(ZnO6)(As3O3)2Mo6O18]4- and [HxAs2Mo6O26](6-x)- clusters as SBUs. AB - By synthesizing the novel molybdenum arsenate complexes, we have obtained eight new structures, namely, (4,4'-bipy)[Zn(4,4' bipy)2(H2O)2]2[(ZnO6)(AsIII3O3)2Mo6O18].7H2O, 1, [Zn(phen)2(H2O)]2[(ZnO6)(AsIII3O3)2Mo6O18].4H2O, 2, [Zn(2,2' bipy)2(H2O)]2[(ZnO6)(AsIII3O3)2Mo6O18].4H2O, 3, [Zn(H4,4' bipy)2(H2O)4][(ZnO6)(AsIII3O3)2Mo6O18].8H2O, 4, (H24,4'-bipy)[CuI(4,4' bipy)]2[H2AsV2Mo6O26].H2O, 5, (H24,4'-bipy)3[AsV2Mo6O26].4H2O, 6, (H24,4' bipy)3[AsV2Mo6O26(H2O)].4H2O, 7, and (H24,4' bipy)2.5(H3O)[AsV2Mo6O26(H2O)].1.25H2O, 8 (4,4'-bipy = 4,4'-bipyridine, 2,2'-bipy = 2,2'-bipyridine, phen = 1,10-phenanthroline). These structures were determined by single-crystal X-ray diffraction analysis and were further characterized by elemental analysis, IR, XPS spectroscopy, and TG analysis. The structure of 1 is constructed from two-dimensional square gridlike sheets linked by the polyanions [(ZnO6)(AsIII3O3)2Mo6O18]4- via hydrogen-bonding interactions to form a three dimensional supramolecular framework with two types of channels. Compounds 2 and 3 display similar bisupported structures. Compound 4 features a three-dimensional supramolecular architecture. Compound 5 possesses a 1D infinite ladderlike ribbon. Compounds 6-8 are discrete structures exhibiting three isomeric forms of [HxAs2Mo6O26](6-x)-. Furthermore, compound 8 represents a new isomer B' [As2Mo6O26(H2O)]6-. In addition, the fluorescent properties of compounds 1-3 are reported. PMID- 17274613 TI - Structural invariance in silver(I) coordination networks formed using flexible four-armed thiopyridine ligands. AB - Two new isomeric, flexible four-armed thioether pyridine-containing ligands 1,2,4,5-tetrakis(3-pyridylmethylsulfanylmethyl)benzene (3tet) and 1,2,4,5 tetrakis(4-pyridylmethylsulfanylmethyl)benzene (4tet) were prepared and characterized. The ligand 3tet gave rise to three isomorphous 3-D networks when reacted with AgClO4 (1), AgPF6 (2), and AgCF3CO2 (3). The topology of the resulting networks was that of the pyrite net. The ligand 4tet gave rise to two isotopological 3-D networks when reacted with AgClO4 (4.2MeCN.2CHCl3) and AgPF6 (5.6MeCN). The topology of these networks was that of the rutile net. A third type of 3-D network of previously unknown topology was formed on reaction with AgCF3SO3 (6.3H2O). The network showed nodes with short topological terms 42.6 and 44.62.87.102. All six networks were binodal and based on three-connected Ag(I) nodes and six-connected ligand-centered nodes. In all of the networks the flexible ligands 3tet and 4tet showed two categories of ligand geometry which in all but one case gave rise to an interligand three-layered pi stack. The networks showed a remarkable lack of dependence on the nature of the counterion and solvent. PMID- 17274614 TI - Lithium, titanium, and zirconium complexes with novel amidinate scorpionate ligands. AB - The reaction of bis(3,5-dimethylpyrazol-1-yl)methane (bdmpzm) with BunLi and carbodiimide derivatives, namely, N,N'-diisopropyl, dicyclohexyl, and 1-tert butyl-3-ethyl carbodiimides, enables the preparation of new heteroscorpionate ligands in the form of the lithium derivatives [Li(NNN)(THF)] (NNN = pbpamd (1) (pbpamd = N,N'-diisopropylbis(3,5-dimethylpyrazol-1-yl)acetamidinate); cbpamd (2) (cbpamd = N,N'-dicyclohexylbis(3,5-dimethylpyrazol-1-yl)acetamidinate); and tbpamd (3) (tbpamd = N-ethyl-N'-tert-butylbis(3,5-dimethylpyrazol-1 yl)acetamidinate)), although a similar process with N,N'-dimethylcarbodiimide gave the dinuclear complex [Li(bpzii)(THF)]2 (4) (bpzii = N-(dimethylamino)-N' [(dimethylamino)bis(3,5-dimethylpyrazol-1-yl)methylimino]imino). When this last reaction was carried out in an air atmosphere, the cluster complex [Li8(mu4 O)2(mu4-OH)2(mu4-pz)2(kappa2-bpziLi)2(bpzCN)2(THF)4] (5) (bpziLi = dimethylaminobis(3,5-dimethylpyrazol-1-yl)methyliminolithium, bpzCN = bis(3,5 dimethylpyrazol-1-yl)acetonitrile) was isolated and characterized by X-ray analysis. Finally, when the same process was carried out in the presence of water the amidine-scorpionate (bpzan) (6) (bpzan = N,N-dimethylbis(3,5-dimethylpyrazol 1-yl)acetamidine) was obtained. Compounds 1 and 3 reacted with [TiCl4(THF)2] or [ZrCl4] to give complexes of stoichiometry [MCl3((kappa3-NNN))] (M = Ti, Zr) (7 10). The structures of the different compounds were determined by spectroscopic methods and, in addition, the X-ray crystal structures of 1, 3, 4, 5, and 6 were also established. PMID- 17274615 TI - Self-assembled architectures from biohybrid triblock copolymers. AB - The synthesis and self-assembly behavior of biohybrid ABC triblock copolymers consisting of a synthetic diblock, polystyrene-b-polyethylene glycol (PSm-b PEG113), where m is varied, and a hemeprotein, myoglobin (Mb) or horse radish peroxidase (HRP), is described. The synthetic diblock copolymer is first functionalized with the heme cofactor and subsequently reconstituted with the apoprotein or the apoenzyme to yield the protein-containing ABC triblock copolymer. The obtained amphiphilic block copolymers self-assemble in aqueous solution into a large variety of aggregate structures. Depending on the protein and the polystyrene block length, micellar rods, vesicles, toroids, figure eight structures, octopus structures, and spheres with a lamellar surface are formed. PMID- 17274616 TI - Top-down solid-phase fabrication of nanoporous cadmium oxide architectures. AB - In this article, we have demonstrated one-step solid-phase transformation from high-quality cadmium carbonate microcrystals into highly nanoporous cadmium oxide. The high crystal quality of cadmium carbonate is critical for the successful fabrication of porous nanoarchitectures with predetermined morphology and well-controlled internal structure. This novel strategy has a good potential to prepare nanoporous materials at a large scale by using perfect monolithic carbonate crystals, and it is also useful to synthesize different nanoporous materials on metal-oxide-coated substrates. Meanwhile, this simple thermal transformation of cadmium carbonate into porous structures has further been extended to convert calcium carbonate into such porous structures. PMID- 17274617 TI - Highly active half-metallocene chromium(III) catalysts for ethylene polymerization activated by trialkylaluminum. PMID- 17274622 TI - Arenes to anilines and aryl ethers by sequential iridium-catalyzed borylation and copper-catalyzed coupling. AB - [reaction: see text] N-Alkyl- and N-arylanilines were synthesized from arenes by a two-step sequence of iridium-catalyzed borylation and copper-catalyzed coupling with amines. Diaryl ethers were obtained by a related sequence of arene borylation, followed by coupling with phenols. In particular, 3,5-disubstituted arylamines and aryl ethers were prepared by initiating this sequence with meta substituted arenes. PMID- 17274618 TI - Balance of structure-building forces in selenium-based self-assembled monolayers. PMID- 17274623 TI - One-pot synthesis of arylboronic acids and aryl trifluoroborates by Ir-catalyzed borylation of arenes. AB - [reaction: see text] The synthesis of arylboronic acids and aryl trifluoroborates in a one-pot sequence by Ir-catalyzed borylation of arenes is reported. To prepare the arylboronic acids, the Ir-catalyzed borylation is followed by oxidative cleavage of the boronic ester with NaIO4. To prepare the aryltrifluoroborate, the Ir-catalyzed borylation is followed by displacement of pinacol by KHF2. These two-step sequences give products that are more reactive toward subsequent chemistry than the initially formed pinacol boronates. PMID- 17274624 TI - Biosynthetic convergence of salinosporamides A and B in the marine actinomycete Salinispora tropica. AB - [structure: see text] Feeding experiments with stable isotopes established that the potent 20S-proteasome inhibitors salinosporamide A and B are biosynthesized in the marine bacterium Salinispora tropica from three biosynthetic building blocks, namely, acetate, beta-hydroxy-2'-cyclohexenylalanine, and either butyrate or a tetrose-derived chlorinated molecule. The unexpected observation that the chlorinated four-carbon residue in salinosporamide A is derived from a different metabolic origin than the non-chlorinated four-carbon unit in salinosporamide B is suggestive of a convergent biosynthesis to these two anticancer natural products. PMID- 17274626 TI - Catalytic asymmetric synthesis of allylic aryl ethers. AB - [reaction: see text] The reaction of trichloroacetimidate derivatives of (Z)-2 alken-1-ols with phenol nucleophiles in the presence of the palladium(II) catalyst [COP-OAc]2 provides 3-aryloxy-1-alkenes in high yields and high enantiomeric purity (typically 63-90% yield and 90-97% ee). The reaction is exemplified by 20 examples. The method employs 1 mol % of the commercially available catalysts (S)- or (R)-[COPOAc]2, produces the branched isomer with unprecedented regioselectivity, and is compatible with the presence of base labile functionality in either reactant. PMID- 17274627 TI - Variability in the structure of rye flour alkali-extractable arabinoxylans. AB - The variability in rye flour alkali-extractable arabinoxylan (AE-AX) structures was examined by extensive fractionation and enzymic degradation studies. AX were isolated from destarched rye water-unextractables by sequential extraction with saturated barium hydroxide solution, water, 1.0 M sodium hydroxide, and water. The isolated AE-AX contained ca. 51% AX with an arabinose to xylose (A/X) ratio of 0.71. Fractionation of the isolated AE-AX by ethanol precipitation yielded a range of AE-AX fractions containing AX molecules with different A/X ratios and substitution patterns. Degradation of these structurally different AE-AX fractions by an Aspergillus aculeatus endoxylanase (XAA) and a Bacillus subtilis endoxylanase (XBS) resulted in AX fragments with various structural features. Further fractionation of the degraded AE-AX fractions by ethanol precipitation showed that a strong correlation exists between the structural features of the AX fragments, that is, average degree of polymerization (DP) of the xylan backbone, A/X ratio, and substitution pattern. Results indicated that the rye flour AE-AX consist of a continuum of structures rather than of two types of AX or two types of regions in the AX molecule. PMID- 17274628 TI - Anti-tobacco mosaic virus (TMV) triterpenoid saponins from the leaves of Ilex oblonga. AB - Ten triterpene saponins have been isolated from a MeOH extract of the leaves of Ilex oblonga. In their structures, six new triterpenoid saponins were named as oblonganosides H-M (2, 4, 5, and 8-10). All structures were elucidated on the basis of spectroscopic analysis. Among the triterpenoid saponins, three compounds (7, 8, and 10) showed obvious activities in inhibiting multiplication of the tobacco mosaic virus (TMV). PMID- 17274629 TI - Anaerobic digestion of wastewater derived from the pressing of orange peel generated in orange juice production. AB - A study of the anaerobic digestion of wastewater from the pressing of orange peel generated in orange juice production was carried out in a laboratory-scale completely stirred tank reactor at mesophilic temperature (37 degrees C). Prior to anaerobic treatment the raw wastewater was subjected to physicochemical treatment using aluminum sulfate as a flocculant and to pH reduction using a solution of sulfuric acid. The reactor was batch fed at COD loads of 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 g of COD. The process was very stable for all of the loads studied, with mean pH and alkalinity values of 7.5 and 3220 mg of CaCO3/L, respectively. The anaerobic digestion of this substrate was found to follow a first-order kinetic model, from which the specific rate constants for methane production, K(G), were determined. The K(G) values decreased considerably from 0.0672 to 0.0078 L/(g h) when the COD load increased from 1.5 to 5.0 g of COD, indicating an inhibition phenomenon in the system studied. The proposed model predicted the behavior of the reactor very accurately, showing deviations of <5% between the experimental and theoretical values of methane production. The methane yield coefficient was found to be 295 mL of CH4 STP/g of COD removed, whereas the mean biodegradability of the substrate (TOC) was 88.2%. A first-order kinetic model for substrate (TOC) consumption allowed determination of the specific rate constants for substrate uptake, K(C), which also decreased with increasing loading, confirming the above-mentioned inhibition process. Finally, the evolution of the individual volatile fatty acid concentrations (acetic, C2; propionic, C3; butyric, C4; isobutyric, iC4; valeric, C5; isovaleric, iC5; and caproic, C6) with digestion time for all loads used was also studied. The main acids generated were acetic and propionic for all loads studied, facilitating the conversion into methane. PMID- 17274631 TI - Respiratory complex I: mechanistic and structural insights provided by the crystal structure of the hydrophilic domain. AB - Complex I of respiratory chains plays a central role in cellular energy production. Mutations in its subunits lead to many human neurodegenerative diseases. Recently, a first atomic structure of the hydrophilic domain of complex I from Thermus thermophilus was determined. This domain represents a catalytic core of the enzyme. It consists of eight different subunits, contains all the redox centers, and comprises more than half of the entire complex. In this review, novel mechanistic implications of the structure are discussed, and the effects of many known mutations of complex I subunits are interpreted in a structural context. PMID- 17274632 TI - Alpha-lipoic acid as a directly binding activator of the insulin receptor: protection from hepatocyte apoptosis. AB - BACKGROUND AND AIM: Alpha-lipoic acid has cytoprotective potential which has previously been explained by its antioxidant properties. The aim of this study was to assess LA-induced-specific cytoprotective signalling pathways in hepatocytes. METHODS: Apoptosis of rat hepatocytes was induced by actinomycinD/TNF-alpha. Caspase-3-like activity was determined by a fluorometric; LDH by an enzymatic assay; and phosphorylation of the insulin receptor, Akt, and Bad by Western blot (after immunoprecipitation). Protein kinase and insulin receptor activities were measured by in vitro phosphorylation. Computer modeling studies were performed by using the program GRID. RESULTS: Alpha-lipoic acid decreased actinomycinD/TNF-alpha-induced apoptosis, as did the antioxidants Trolox and N-acetylcysteine. The activation of PI3-kinase/Akt involving phosphorlyation of Bad markedly contributed to the cytoprotective action of alpha lipoic acid. Alpha-lipoic acid but not other antioxidants protected against actinomycinD/TNF-alpha-induced apoptosis via phosphorylation of the insulin receptor. Computer modeling studies revealed a direct binding site for alpha lipoic acid at the tyrosine kinase domain of the insulin receptor, suggesting a stabilizing function in loop A that is involved in ATP binding. Treatment of immunoprecipitated insulin receptor with LA induced substrate phosphorylation. CONCLUSIONS: Alpha-lipoic acid mediates its antiapoptotic action via activation of the insulin receptor/PI3-kinase/Akt pathway. We show for the first time a direct binding site for alpha-lipoic acid at the insulin receptor tyrosine kinase domain, which might make alpha-lipoic acid a model substance for the development of insulin mimetics. PMID- 17274633 TI - Salt concentration and pH-dependent adsorption of two polypeptides on planar and divided alumina surfaces. In situ IR investigations. AB - The adsorption of proteins is the first process to take place when a solid is immersed in a biological fluid; though not yet thoroughly understood at a molecular level, this process is also known to be strongly influenced by the presence of salt in solution or by pH changes. In the present work, poly-L glutamic acid (PG) and poly-L-lysine (PL) were selected to mimic the behavior of some protein fragments. Their adsorption was investigated by infrared spectroscopy in various modes, both on planar and on divided (powder) surfaces of aluminum oxide. These two peptides were shown to have different behaviors when adsorbed from solutions with or without CaCl2 and at various pH values. Polarization modulation-reflection absorption infrared spectroscopy, applied in a special cell designed to characterize the solid surface in contact with the liquid, enabled the observation of the influence of pH and salts upon polypeptide adsorption. At pH values higher than 5 and in the presence of CaCl2 in solution, a net increase of the PG adsorbed amount is observed, whereas no such effect could be detected for PL. Specific interactions between the COO- groups on the side chains and the surface, or between those of two different molecules, was inferred. Interestingly, similar conclusions could be drawn for the surface of alumina powders contacted with solutions of PG and PL and characterized by attenuated total reflectance IR. This work demonstrates the potential for IR investigations of solid oxide-liquid interfaces combining the study of planar and finely divided surfaces. PMID- 17274630 TI - Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex. AB - The mechanisms by which multisubunit histone acetyltransferase (HAT) complexes recognize and perform efficient acetylation on nucleosome substrates are largely unknown. Here, we use a variety of biochemical approaches and compare histone based substrates of increasing complexity to determine the critical components of nucleosome recognition by the MOZ, Ybf2/Sas3, Sas2, Tip60 family HAT complex, Piccolo NuA4 (picNuA4). We find the histone tails to be dispensable for binding to both nucleosomes and free histones and that the H2A, H3, and H2B tails do not influence the ability of picNuA4 to tetra-acetylate the H4 tail within the nucleosome. Most notably, we discovered that the histone-fold domain (HFD) regions of histones, particularly residues 21-52 of H4, are critical for tight binding and efficient tail acetylation. Presented evidence suggests that picNuA4 recognizes the open surface of the nucleosome on which the HFD of H4 is located. This binding mechanism serves to direct substrate access to the tails of H4 and H2A and allows the enzyme to be "tethered", thereby increasing the effective concentration of the histone tail and permitting successive cycles of H4 tail acetylation. PMID- 17274634 TI - Homogeneous, core-shell, and hollow-shell ZnS colloid-based photonic crystals. AB - Ordered ZnS-based colloidal crystals from homogeneous, core-shell, and hollow building blocks were prepared via electrosteric colloid stabilization combined with a convective assembly technique. The polyelectrolyte stabilized colloids assembled into face-centered cubic arrays with the (111) face perpendicular to the substrate. Structure-property correlations were made using scanning electron microscopy, scanning transmission electron microscopy, and UV/visible/near-IR spectroscopy. Multilayer film growth, with film thickness of several micrometers, was achieved. Optical spectra showed (111) stopgaps along with pronounced higher order peaks. The spectral position of the photonic stopgap can be predicted using a volume average refractive index and the Maxwell-Garnett formula for the homogeneous and core-shell particles, respectively. This work holds the promise of harnessing ZnS for optical property engineering and enhanced photonic band gap materials. PMID- 17274635 TI - Elastin-calmodulin scaffold for protein microarray fabrication. AB - In this work, we report a new method to reversibly immobilize proteins to a surface in a functionally active orientation directly from cell lysate by employing a fusion protein consisting of a thermal-responsive elastin (ELP) domain as the surface anchor and a calcium-responsive calmodulin (CalM) domain for protein capturing. Incorporation of an M13 tag into recombinant proteins enables not only easy surface immobilization but also direct purification from cell lysates. The feasibility of concept was demonstrated using the M13-tagged yellow fluorescent protein (M13-YFP). The ELP-CalM functionalized surfaces were shown to capture M13-YFP directly from cell lysate through the specific calmodulin-M13 association in a calcium-dependent manner. We also demonstrated that immobilization is reversible; the bound proteins were released from the surface in the presence of EDTA. PMID- 17274636 TI - Thermal immobilization of ferrocene derivatives on (111) surface of n-type silicon: parallel between vinylferrocene and ferrocenecarboxaldehyde. AB - Monolayers attached to a Si(111) surface through Si-C-C or Si-O-C covalent bonds were prepared by the thermally activated reaction (150 degrees C) of vinylferrocene (VFC) or ferrocenecarboxaldehyde (FCA) molecules with hydrogen terminated Si(111) substrate in order to compare their reactivities. The resulting monolayers gave a couple of redox waves on voltammograms due to ferrocenyl moieties tethered at the surface. The voltammetric quantification revealed that the growth of electrochemically active layers was terminated within 5 h and the final surface coverages of the active ferrocenyl moieties were 58% and 16% for VFC- and FCA-based monolayers, respectively, indicating that the aldehyde molecule is less reactive. X-ray photoelectron spectroscopy and ellipsometry, however, gave an indication that the growth of the VFC layer did not self-terminate and proceeded beyond a monolayer, while this overgrown part of the layer was not electrochemically active. PMID- 17274637 TI - Fabrication of gradient mesostructures by Langmuir-Blodgett rotating transfer. AB - In this letter, we present a simple yet novel method, Langmuir-Blodgett (LB) rotating transfer, to achieve a continuous gradient mesostructure in a well ordered fashion over large areas. A mixed monolayer of phospholipid and dye is chosen as a model system to test the feasibility of LB rotating transfer to fabricate continuous gradient structures, which is confirmed by the simulation and experimental results. The technique presented here to obtain gradient structures is low-cost and high-throughput and can be extended to other systems of LB patterning. PMID- 17274638 TI - Correlation between fundamental binding forces and clinical prognosis of Staphylococcus aureus infections of medical implants. AB - Atomic force microscopy was used to "fish" for binding reactions between a fibronectin-coated probe (i.e., substrate simulating an implant device) and each of 15 different isolates of Staphylococcus aureus obtained from either patients with an infected cardiac prosthesis (invasive group) or healthy human subjects (control group). There is a strong distinction (p = 0.01) in the binding-force signature observed for the invasive versus control populations. This observation suggests that a microorganism's "force taxonomy" may provide a fundamental and practical indicator of the pathogen-related risk that infections pose to patients with implanted medical devices. PMID- 17274639 TI - Solubilization of Paclitaxel (taxol) by peptoad self-assemblies. AB - A molecular dynamics simulation was carried out involving a paclitaxel molecule, 987 peptoad molecules, and 35 938 water molecules (conditions shown experimentally to effect paclitaxel solubilization in water). The peptoads are shown to form large clumps, the centers of which are dry and thus favorable to hydrogen bonding between paclitaxel and peptoads. Hydrogen-bonding equilibrium among the peptoads themselves in the developing clumps is achieved in 2 ns. The number and position of hydrogen bonds between the paclitaxel and peptoads fluctuate randomly from two to six within a 2-5 ns time frame. Hydrophobic association between the peptoad chains and the apolar paclitaxel groups does not seem to be an important element of the solubilization. Instead, the hydrophobic chains of the peptoads encasing the paclitaxel extend outward into the dry interior of the peptoad clump where other chains in the clump are located. One hopes that studies such as this will ultimately allow rational predictions when designing new and specific drug solubilizers. PMID- 17274640 TI - A limited screen for protein interactions reveals new roles for protein phosphatase 1 in cell cycle control and apoptosis. AB - Protein phosphatase 1 (PP1) catalytic subunits typically combine with other proteins that modulate their activity, direct them to distinct substrates, or serve as substrates for PP1. More than 50 PP1-interacting proteins (PIPs) have been identified so far. Given there are approximately 10 000 phosphoproteins in mammals, many PIPs remain to be discovered. We have used arrays containing 100 carefully selected antibodies to identify novel PIPs that are important in cell proliferation and cell survival in murine fetal lung epithelial cells and human A549 lung cancer cells. The antibody arrays identified 31 potential novel PIPs and 11 of 17 well-known PIPs included as controls, suggesting a sensitivity of at least 65%. A majority of the interactions between PP1 and putative PIPs were isoform- or cell type-specific. We confirmed by co-immunoprecipitation that 9 of these proteins associate with PP1: APAF-1, Bax, E-cadherin, HSP-70, Id2, p19Skp1, p53, PCNA, and PTEN. We examined two of these interactions in greater detail in A549 cells. Exposure to nicotine enhanced association of PP1 with Bax (and Bad), but also induced inhibitory phosphorylation of PP1. In addition to p19Skp1, PP1alpha antibodies also coprecipitated cullin 1, suggesting that PP1alpha is associated with the SCF1 complex. This interaction was only detectable during the G1/S transition and S phase. Forced loss of PP1 function decreased the levels of p27Kip1, a well-known SCF1 substrate, suggesting that PP1 may rescue proteins from ubiquitin/proteasome-mediated destruction. Both of these novel interactions are consistent with PP1 facilitating cell cycle arrest and/or apoptosis. PMID- 17274641 TI - Apparent and standard partial molar volumes of NaCl, NaOH, and HCl in water and heavy water at T = 523 K and 573 K at p = 14 MPa. AB - Apparent molar volumes, Vphi,2, of aqueous NaCl, NaOH, NaOD, HCl, and DCl in water and heavy water were determined at T = 523 and 573 K and p = 14 MPa with a high-temperature platinum vibrating-tube densimeter in the aquamolality range 0.25 50:1 approximately >20:1) and yields (79 approximately 74%) were achieved for the key glycosidation steps. The exceptionally high alpha selectivity observed was shown to be consequent to the selective anomerization of beta- to alpha-anomer under the glycosidation conditions. This glycosidation is well suited for a highly convergent oligosaccharide synthesis, particularly because of excellent chemical yields even when using approximately equal-sized donors and acceptors in an approximately 1:1 molar ratio. An iterative reaction sequence allowed the growing oligosaccharide to double in size after each cycle and led to an efficient synthesis of sMMP 8-, 12-, and 16-mers 18-20. PMID- 17274660 TI - Mechanistic insights into the palladiumII-catalyzed hydroxyalkoxylation of 2 allylphenols. AB - The Pd(OCOCF3)2/[(HOCH2CH2NHCOCH2)2NCH2]2-catalyzed oxidation of o-allylphenol with H2O2 in water/methanol affords a syn and anti mixture of 2-(1,2 dihydroxypropyl)phenol and 2-(2-hydroxy-1-methoxypropyl)phenol. Mechanistic experiments and ESI-MS studies support a pathway wherein isomerization of the C=C bond followed by its epoxidation and oxirane opening led to the products. Recycling of the catalytic system led to gradual lost of activity. PMID- 17274659 TI - N-isopropylidene-N'-2-nitrobenzenesulfonyl hydrazine, a reagent for reduction of alcohols via the corresponding monoalkyl diazenes. AB - The reagent N-isopropylidene-N'-2-nitrobenzenesulfonyl hydrazine (IPNBSH) is used in the reduction of alcohols via the loss of dinitrogen from transiently formed monoalkyl diazene intermediates accessed by sequential Mitsunobu displacement, hydrolysis, and fragmentation under mild reaction conditions. PMID- 17274662 TI - Methods of delivery to antigen-presenting cells: development of new and improved vaccines. PMID- 17274661 TI - Intracellular distribution of TiO2-DNA oligonucleotide nanoconjugates directed to nucleolus and mitochondria indicates sequence specificity. AB - Deoxyribonucleic acid (DNA) oligonucleotides hybridize to matching DNA sequences in cells, as established in the literature, depending on active transcription of the target sequence and local molarity of the oligonucleotide. We investigated the intracellular distribution of nanoconjugates composed of DNA oligonucleotides attached to TiO2 nanoparticles, thus creating a locally increased concentration of the oligonucleotide. Two types of nanoconjugates, with oligonucleotides matching mitochondrial or nucleolar DNA, were specifically retained in mitochondria or nucleoli. PMID- 17274663 TI - Vaccine delivery methods using viral vectors. AB - Viral vectors have different capabilities as gene delivery vehicles for vaccines and immunotherapeutics. This review discusses selected viral vector systems and plasmid DNA and provides an overview of their specific characteristics, strengths, and limitations. The features, modes of viral entry and replication, expression of heterologous proteins, issues related to both preexisting and heterologous immunity, and vaccine strategies are discussed for the different vectors. Comparisons of the features and capabilities of the vectors are provided. PMID- 17274664 TI - Controlled release biopolymers for enhancing the immune response. AB - Controlled release of biologically active compounds in the context of drug and vaccine delivery is an important area of research with broad implications in many areas of medicine. In particular, the challenges of oral delivery are of specific interest to reduce the cost and potential health risks related to parenteral administration of pharmaceuticals and vaccine formulations. We discuss the biological activities of two biopolymers, beta-glucans and emulsans, both of which offer significant potential for individual formulations related to drug impact, while in combination offer synergistic opportunities in terms of formulation and delivery. beta-Glucans have been established as potent immunomodulatory and biologically active compounds with application in a wide range of disease systems. The emulsan family of biopolymers also has significant potential in vaccine and drug delivery based on recent studies. Each of these biopolymers offers exciting opportunities to modulate biological responses via control of chemistry and physical properties achieved during biosynthesis or postsynthesis modifications. When combined into a delivery system for controlled release, synergistic outcomes may be achieved that offer new and exciting opportunities as described in the present paper. These outcomes represent the combined improvements of solubility in physiological environments and immunomodulation due to the specific chemistry and structures involved. Overall, this approach provides a new direction in controlled release wherein the biomaterial carrier, in this case emulsan, and the drug, in this case beta glucan, play an active role both in biological activation as well as in delivery profiles. PMID- 17274665 TI - Type 1 and 2 immunity following vaccination is influenced by nanoparticle size: formulation of a model vaccine for respiratory syncytial virus. AB - Previous studies compared uptake by dendritic cells (DC) of 20, 40, 100, 200, 500, 1000, and 2000 nm beads in vivo. When beads were used as antigen carriers, bead size influenced antibody responses and induction of IFN-gamma-producing CD4 and CD8 T cells. Beads of 40-50 nm were taken up preferentially by DC and induced particularly strong immunity. Herein, we examine immunity induced by minute differences in nanobead size, specifically within a narrow viral-sized range (20, 40, 49, 67, 93, 101, and 123 nm), to see if bead carrier size influenced the induction of type 1 or type 2 cells as demonstrated by the production of IFN gamma or IL-4. In vivo uptake by DC was assessed for selected sizes in this range. Responses to whole ovalbumin (OVA) or the OVA-derived CD8 T cell peptide epitope (SIINFEKL) were tested. After one immunization with beads-OVA, IFN-gamma responses to both OVA and SIINFEKL were significantly better with 40 and 49 nm beads than other sizes, while, in contrast, IL-4 responses to OVA were higher after immunization with OVA conjugated to larger beads (93, 101, and 123 nm). Thus IFN-gamma induction from CD8 T cells was limited to 40-49 nm beads, while CD4 T cell activation and IL-4 were induced by 93-123 nm beads-OVA. After two immunizations, there were comparable high levels of IFN-gamma produced with 40 and 49 beads and IL-4 reactivity was still higher for larger beads (93, 101, 123 nm). Production of IgG1 was seen across the full range of bead sizes, increasing after two immunizations. Since protection against respiratory syncytial virus (RSV) depends on strong IFN responses, while IL-4 responses are reported to cause asthma-like symptoms, immunization with RSV antigens on the 49 nm carrier beads could provide the basis for a suitable vaccine. When the 49 nm beads were conjugated to RSV proteins G88 (surface) or M2.1 (internal capsid), one immunization with G88 induced high levels of IFN-gamma and low levels of IL-4. IL 4 increased with two immunizations. Beads-M2.1 induced only moderate levels of IFN-gamma and low titer antibody after two immunizations. Mice vaccinated once with G88-conjugated 49 nm beads and challenged intranasally with RSV strain A2 subtype showed reduced viral titers and recovered from weight loss more rapidly than mice immunized with M2.1-conjugated 49 nm beads or naive control mice. These results show that precise selection of nanobead size for vaccination can influence the type 1/type 2 cytokine balance after one immunization, and this will be useful in the development of effective vaccines against common human pathogens such as RSV. PMID- 17274666 TI - Identification of influx transporter for the quinolone antibacterial agent levofloxacin. AB - Quinolone antibacterial agents exhibit high intestinal absorption, selective tissue distribution, and renal and biliary excretion. Several ATP-binding cassette transporters are involved in efflux transport of these agents, but no influx transporters have yet been molecularly identified. In the present study, we aimed to identify the influx transporter(s) of quinolone antibiotics using levofloxacin as a model compound. Several candidate transporter genes were selected based on differential expression of mRNAs among Caco-2 cell subclones that exhibited differential uptake activities for levofloxacin. Based on a functional analysis of each transporter gene for which a good correlation was found between expression level and levofloxacin transport activity in the Caco-2 subclones, organic anion transporting polypeptide 1A2 (OATP1A2 (OATP-A), SLCO1A2) was concluded to transport levofloxacin. When OATP1A2 was expressed in Xenopus oocytes, levofloxacin transport was essentially pH-independent and was not stereoselective. OATP1A2-mediated uptake of levofloxacin showed a K(m) value of 136 microM. Apparent uptake of levofloxacin by Caco-2 cells showed high- and low affinity components with K(m) values of 0.489 and 14.6 mM, respectively. Accordingly, plural transporters are functional for the transport of levofloxacin in Caco-2 cells, and OATP1A2 is likely to function as a high-affinity transporter. The inhibitory effects and the expression of transport activity of other quinolone antibacterial agents suggested that OATP1A2 commonly transports all the agents tested. In conclusion, this is the first identification of an influx transporter for fluoroquinolones, and the results suggest that active influx transport at least partially explains the high membrane permeability of the quinolone agents in various tissues. PMID- 17274667 TI - Bile acid-oligopeptide conjugates interact with DNA and facilitate transfection. AB - Bile acids conjugated to oligoarginine-containing peptides (BACs) form complexes with DNA based on the electrostatic interactions between negatively charged phosphate groups of the nucleic acid and the positively charged side chain guanidinium groups of the oligoarginine in the BACs. Charge neutralization of both components and subsequent increases of the net positive charge of the complex combined with the water-soluble lipophilic nature of the bile acid results in changes in the physicochemistry and biological properties of the complexes. We have examined the relationship of a series of 13 BACs on their interaction with circular plasmid DNA (pDNA). The formation of soluble, low density and insoluble, high-density complexes was analyzed using several methods. The formation of high-density complexes was dependent on the DNA concentration, and was enhanced by increasing the BAC to pDNA charge ratio. Several of the BAC:pDNA complexes demonstrated exclusion of the DNA-intercalator Hoechst 33258 from pDNA, and were also protected from DNase activity. Several BAC conjugates interacted with pDNA to form nanometer-sized particles suitable for cell transfection in vitro. Five of the 13 BACs were transfection competent as single agents, and 11 of the 13 BACs showed enhancement of transfection in combination with DOPE containing liposomes or silica nanoparticles. PMID- 17274668 TI - Pore closing and opening in biodegradable polymers and their effect on the controlled release of proteins. AB - The purpose of this paper was to investigate the phenomena of pore closing and opening in microspheres of poly(lactic-co-glycolic acid) (PLGA) and PLGA-glucose star copolymer (PLGA-Glu) and their effects on protein release. We used scanning electron microscopy (SEM) and laser scanning confocal microscopy (LSCM) to visually characterize the pore state and the uptake of dextran labeled with pH insensitive probes by microspheres, as an indicator of pore connectivity. The effect of temperature on initial protein release from microspheres was also investigated. It was found that (1) pore closing occurs in both PLGA and PLGA Glu; (2) pore closing can take place at later time during incubation at physiological condition (37 degrees C) as well as during the initial stage; (3) pore closing is much more significant at elevated temperatures; (4) previously isolated pores can become open by, for example, osmotic-mediated events; and (5) pore closing/opening correlates with the release rate of biomacromolecules from PLGA or PLGA-Glu microspheres. The pore closing/opening appeared potentially a universal event throughout the release period dictating the kinetics of protein release from PLGA microspheres. Hence, these results strongly suggest that open and isolated pores are able to toggle back-and-forth periodically during PLGA degradation while controlling protein release; these observations imply a novel new hypothesis concerning erosion-controlled release of biomacromolecules from PLGA and related polymers. PMID- 17274669 TI - Evaluation of an LC8-binding peptide for the attachment of artificial cargo to dynein. AB - The limited cytoplasmic mobility of nonviral gene carriers is likely to contribute to their low transfection efficiency. This limitation could be overcome by mimicking the viral strategy of recruiting the dynein motor complex for efficient transport toward the host cell nucleus. A promising approach for attaching artificial cargo to dynein is through an adaptor peptide that binds the 8 kDa light chain (LC8) found in the cargo-binding region of the dynein complex. Several viral proteins that bind LC8 have in common an LC8-binding motif defined by (K/R)XTQT. Short peptides containing this motif have also been shown to bind recombinant LC8 in vitro. However, since the majority of intracellular LC8 exists outside of the dynein complex, it remains unclear whether peptides displaying this LC8-binding motif can access and bind to dynein-associated LC8. In this study, we employed biochemical analysis to investigate the feasibility of attaching artificial cargo to the dynein motor complex using a peptide displaying the well-characterized LC8-binding motif. We report that free intracellular LC8 bound specifically to an LC8-binding (TQT) peptide and not to a control peptide with a mutated LC8-binding motif. However, a similar binding interaction between the TQT peptide and intracellular dynein was not detected. To determine whether dynein binding of the TQT peptide was prevented by competition with free intracellular LC8 or due to the inability of the peptide to access its LC8 binding site in the dynein complex, the TQT peptide was evaluated for its ability to bind either purified LC8 or purified dynein. Our results demonstrate that, while the TQT peptide readily binds free LC8, it cannot bind to dynein-associated LC8. The results emphasize the need to identify functional dynein-binding peptides and highlight the importance of designing peptides that bind to the intact dynein motor complex. PMID- 17274670 TI - Transcriptionally targeted nonviral gene transfer using a beta-catenin/TCF dependent promoter in a series of different human low passage colon cancer cells. AB - Nonviral transfections of six low passage human colon cancer cell lines using the artificial beta-catenin/TCF-dependent promoter CTP4 demonstrated a high promoter activity which was 1000- to 70000-fold higher than in HeLa control cells. Luciferase gene expression levels obtained with CTP4 in epithelial-like tumor cell cultures were only slightly lower than with the strong viral CMV promoter/enhancer, whereas in less differentiated tumor cultures CTP4 expression levels exceeded the CMV expression levels up to 28-fold. Three cell lines representing different morphology typical of the original tumors, more differentiated epithelial-like (COGA-5), piled-up (COGA-12), and poorly differentiated rounded-up (COGA-3), were selected for further investigation. Gene transfer was optimized using lipopolyplex formulation of cationic lipid DOSPER and polycation PEI25br. Lipopolyplexes enabled up to 1300-fold or 400-fold higher luciferase expression compared to the corresponding lipoplexes or polyplexes, respectively. Lipopolyfection of an interleukin-2 (IL-2) gene expression construct driven by the CTP4 promoter resulted in very high levels of up to 95 ng of secreted IL-2 per 105 cells and 24 h. The lipopolyplexes were also able to transfect multicellular spheroids that mimic the three-dimensional structure of real tumors. PMID- 17274671 TI - Modifying the sugar moieties of daunorubicin overcomes P-gp-mediated multidrug resistance. AB - Anthracyclines are widely used in patients for anticancer activity. However, one of the limitations for their clinical use is P-gp-mediated drug resistance in cancer therapy. We hypothesize that modified anthracyclines will retain their anticancer activity, avert P-gp binding, and thus overcome P-gp-mediated drug resistance. Twenty-five daunorubicin analogues were synthesized with slight structure modifications in sugar moieties. Molecular docking, cytotoxicity, and P gp inhibition assays in drug-resistant leukemia cells (K562/Dox) were used to identify several candidates that avert binding to multidrug-resistant protein (MsbA) and overcome drug resistance. Molecular docking showed that daunorubicin bound to the cavity between the intracellular domain (ICD) and nucleoside binding domain (NBD) of MsbA, which might be the "entry site" for the transport of its substrate. The molecular docking accurately predicted the substrates of multidrug resistant protein. Several aspects are important for daunorubicin analogue binding to MsbA: (1) the substitution pattern and stereochemistry of the tetracyclic ring and sugar moiety; (2) the hydrogen bond donor or acceptor capability of the substituent at C'-3 and C'-4. Molecular docking, cytotoxicity, and P-gp inhibition assays identified ADNR, ADNR-1, and ADNR-3 for averting P-gp binding and overcoming drug resistance. The replacement of C'-3-NH2 with azido group in daunorubicin not only abolishes the hydrogen bond between the sugar moiety and MsbA but also completely changes the overall binding conformation, and thus averts the binding to MsbA. Cytotoxicity assays confirmed that these compounds showed high sensitivity against drug-resistant cancer cells (K562/Dox) with P-gp overexpression. P-gp inhibition assay indeed confirms that these appropriately modified compounds avert P-gp binding and thus overcome P-gp mediated drug resistance. PMID- 17274673 TI - OCTN2-mediated carnitine uptake in a newly discovered human proximal tubule cell line (Caki-1). AB - The proximal tubular reabsorption of carnitine in the human kidney is significant because more than 95% of the carnitine filtered in the kidney is reabsorbed by the proximal tubules therefore maintaining the homeostatic balance of carnitine in the body. Objectives of this study include the characterization of OCTN2 function in the Caki-1 cell line and the potential interactions of carnitine uptake with renally secreted drugs, including drugs of quaternary ammonium structure. Caki-1 cells were additionally characterized to be of proximal tubule nature, and an apical membrane expression pattern of OCTN2 in Caki-1 cells was discovered. Uptake studies with radiolabeled L-carnitine in Caki-1 cells revealed a Na+- and temperature-dependent carrier-mediated process (K(m) = 15.90 microM) which was unaffected by pH in a range from 6.5 to 8.5. All drugs tested were able to inhibit the carnitine uptake process to different degrees. The quaternary ammonium compounds ciclotropium bromide and ipratropium bromide were strong inhibitors with IC(50) values of 30 microM and 95 microM, respectively. The observed kinetics, immunohistolocalization, and inhibition studies indicate that the high-affinity uptake of carnitine in the Caki-1 cell line is most likely mediated by OCTN2. The interaction of drugs at the renal level with OCTN2 indicates a possible pathway for the final step of cationic secretion into the urine. PMID- 17274672 TI - Exposure of cells to hydrogen peroxide can increase the intracellular accumulation of drugs. AB - One of the fastest growing areas of scientific research involves aspects of oxidative stress, either causes of or results from. Despite the enormous quantity of literature on the topic, surprisingly, the effects of oxidative stress on the pharmacokinetics of drugs have not been previously investigated. This is an extremely important concern, considering that the degree of oxidative stress that the human body experiences is known to be widely variable. Oxidative stress may be transiently increased, as is the case with some inflammatory episodes, or it may be chronically elevated, as is the case in some disease states, in aging, or with smokers. This report examines the influence of oxidative stress on the pharmacokinetics of model drugs utilizing cells in culture. Specifically, the effect of subtoxic, short-term exposure to hydrogen peroxide was investigated. Low micromolar, single doses of hydrogen peroxide were shown to cause dramatic increases in the apparent intracellular accumulation of model compounds with different physicochemical properties in different cell types. To examine the mechanistic basis for this, we evaluated possible hydrogen peroxide induced changes in cells including (1) intracellular pH, (2) membrane integrity, and (3) membrane fluidity (i.e., lateral membrane diffusion). We found no significant changes in pH or membrane integrity, but results were consistent with changes in hydrogen peroxide mediated reductions in lateral membrane diffusion, which we postulate facilitated the accumulation of the test substrates. Although studies presented here were all done in cell culture systems, we believe the findings could have substantial therapeutic relevance and warrant further investigations, which may provide reasons why drugs often have anomalous pharmacokinetic behavior and disproportionate dose-response relationships in certain patient populations. PMID- 17274675 TI - Functional half-life is a meaningful descriptor of steady-state pharmacokinetics of an extended-release formulation of a rapidly cleared drug : as shown by once daily divalproex-ER. AB - BACKGROUND: For many drugs, steady-state concentration-time profiles are often not optimally characterised by the intrinsic terminal elimination half-life for various reasons, including multiexponential disposition with minimal contribution of the terminal phase to steady-state exposure or use of controlled-release formulations with extended zero- or mixed zero-/first-order absorption. In such cases, 'effective' or 'functional' half-life (t((1/2)F)) has often been used to characterise steady-state pharmacokinetics. Valproic acid, commonly used in neuropsychiatry, has an elimination half-life of 4-16 hours in different populations (children vs adults, enzyme-induced vs uninduced). Divalproex-ER, a once-daily extended- release divalproex sodium formulation, is designed to release valproic acid over >18 hours. Hence the steady-state divalproex-ER concentration-time profiles have small peak-trough fluctuations that are not optimally characterised by valproic acid elimination half-life. In this study, the value of t((1/2)F) was calculated to characterise divalproex-ER steady-state concentration-time profiles. METHODS: The value of t((1/2)F), defined as the time taken for the concentration to drop by one-half during a dosing interval (tau) at steady state, was derived using steady-state maximum (C(max)) and minimum (C(min)) plasma concentration and tau values, and calculated as ln(2)/(ln [C(max)/C(min)]/tau). The t((1/2)F) values of valproic acid in adult hepatic enzyme-uninduced healthy subjects and enzyme-induced epilepsy patients were calculated from five pharmacokinetic studies in which divalproex-ER was administered once daily for 6-14 days. RESULTS: The estimated geometric mean t((1/2)F) in uninduced adults was 40.0 hours versus the expected elimination half life of 12-16 hours in this population (including patients on valproic acid monotherapy); for induced patients, t((1/2)F) was 26.9 hours versus the expected elimination half-life of 6-12 hours. CONCLUSION: The t((1/2)F) of valproic acid optimally characterises the expected steady-state C(max) to C(min )decrease of 33% in uninduced and 45% in induced adults following once-daily administration of divalproex-ER. PMID- 17274676 TI - Neoadjuvant treatment with paclitaxel and epirubicin in invasive breast cancer: a phase II study. AB - BACKGROUND AND OBJECTIVES: The modern management of locally advanced breast cancer includes a multimodal approach consisting of neoadjuvant chemotherapy (usually given as initial treatment), surgery, radiotherapy and adjuvant hormone therapy. This therapeutic approach converts many patients with initially unresectable disease to reasonable surgical candidates, with acceptable rates of loco-regional disease control. Induction of a pathological complete response (pCR) with modern chemotherapy agents or combined with immunotherapy, when applicable, should be one of the primary goals of neoadjuvant therapy in order to achieve better disease-free and overall survival in this subset of patients. Neoadjuvant chemotherapy is now standard for patients with locally advanced breast cancer, and this method of treatment has been extended to patients with earlier disease without affecting the treatment outcome. The objectives of this study were: (1) to conduct a phase II study to assess the efficacy and availability of epirubicin and paclitaxel in the neoadjuvant setting in women with locally advanced or high tumour-to-breast ratio breast cancer (no patient in either of these subgroups was a candidate for breast-conserving surgery prior to chemotherapy); (2) to evaluate the incidence of clinically relevant toxicity and, in particular, cardiac toxicity after treatment with an epirubicin + paclitaxel regimen in this group of patients. METHODS: In this open-label, phase II, single centre trial carried out in a university-affiliated tertiary-care municipal hospital, the rate of objective response, evaluated by clinical and pathological examinations, was the primary endpoint of the study. Other endpoints were the rates of breast-conserving surgery, local recurrence, disease-free survival and overall survival. Sixty patients were enrolled from September 1998 to September 2003 with a median follow-up of 56 months (range 16-96). All 60 women met the criteria for inclusion and agreed to participate in the study. They were diagnosed as having locally advanced or high tumour-to-breast ratio breast cancer that did not initially permit breast-conserving surgery. Epirubicin 75 mg/m(2) and paclitaxel 175 or 200 mg/m(2) were administered for five courses. Rates of adverse events were also analysed. RESULTS: Eight patients experienced a pCR, five had a pathological partial response with an almost complete pathological response, and 39 were able to undergo breast-conserving surgery. Adverse effects were mostly of grade 1 or 2 severity. The most common adverse reactions were fatigue and neutropenic fever. One patient developed local recurrence during the median 56-month follow-up. Among examined biological markers, only estrogen receptor negativity was a strong predictor of a pCR. The rates of disease-free and overall survival following the neoadjuvant combination were similar for those who had tumours positive for the estrogen receptor and those who were negative for this. CONCLUSION: Treatment with a combination of epirubicin and paclitaxel enabled lumpectomy in a substantial proportion of women who were previously deemed to not be suitable candidates for breast-conserving surgery. Clinical responses were not influenced by the initial tumour volume, and the only statistically significant predictor of pCR was the estrogen receptor status of the tumour. PMID- 17274677 TI - Comparison of diurnal intraocular pressure control by latanoprost versus travoprost : results of an observational survey. AB - BACKGROUND AND OBJECTIVE: Intraocular pressure (IOP) is known to be subject to daily fluctuations, the occurrence of which is a risk factor for progression of glaucoma. Control of IOP during the day by drugs is an important therapeutic target. We set out to compare the IOP control of travoprost and latanoprost taking into account the time since last instillation and the time of IOP measurement. METHODS: This was a prospective, cross-sectional observational study with some retrospective data collection. Private ophthalmologists were selected to each recruit ten patients with primary open-angle glaucoma and/or ocular hypertension receiving either travoprost or latanoprost as monotherapy. Clinical endpoints included IOP measurements and percentage of patients attaining predefined target IOPs. Six patient subgroups were defined according to: (a) IOP measurement time: before 1200h, 1200h-1600h and after 1600h, and (b) time since last intake (<24 hours, >24 hours). Analyses comprised chi(2) and Wilcoxon tests, ANOVA, logistic regressions and adjustment by propensity score. RESULTS: In total, 2052 patients treated with travoprost (n = 1704) or latanoprost (n = 348) participated in the study. Treatment groups were comparable at baseline, except for a longer treatment duration in latanoprost-treated patients. When the interval between the last treatment instillation and IOP measurement (treatment/IOP interval) was <24 hours (n = 1241), 82% of travoprost-treated patients attained pre-defined target IOP versus 67% with latanoprost (p < 0.0001). This difference was greatest after 1600 h, when the mean IOP was 16.5 mm Hg for travoprost-treated patients and 17.7 mm Hg for latanoprost-treated patients (p = 0.0025). When the treatment/IOP interval was >24 hours (n = 461), travoprost was superior to latanoprost, i.e. more patients using travoprost attained the predefined target IOP (78.5% vs 68.3%; p = 0.0344), and the mean IOP value was lower in the travoprost group (16.8 vs 17.8 mm Hg; p = 0.0016). After adjustments for confounding factors, similar results were obtained. CONCLUSIONS: According to this observational survey, travoprost appears to reduce evening and mean diurnal IOP more effectively than latanoprost. Latanoprost IOP control appears to be more sensitive to time since the last dose. PMID- 17274678 TI - Evaluation of chromogranin A expression in patients with non-neuroendocrine tumours. AB - BACKGROUND: Chromogranin A (CgA) is well established as a serum marker for neuroendocrine tumours and has also been associated with some non-neuroendocrine tumours, suggesting a possible role for somatostatin analogues such as octreotide in the treatment of these tumours. OBJECTIVE: The aim of this study was to measure plasma CgA levels in patients with various non-neuroendocrine tumours in order to identify those patients who might benefit from octreotide therapy. METHODS: Plasma CgA levels were tested in 151 patients with metastatic non neuroendocrine tumours. Patients with highly elevated levels were assessed by OctreoScan scintigraphy to determine their somatostatin receptor status, and those with positive results were offered treatment with the somatostatin analogue octreotide, 20 mg every 4 weeks, and followed up every 3 months. RESULTS: CgA levels were elevated (>18 U/L) in 34/72 patients with breast cancer, 11/21 with lung cancer, 10/28 with gastrointestinal cancer, 7/12 with gynaecological cancer, 6/9 with genitourinary cancer, 5/5 with haematological cancer, and 3/4 with head and neck cancer. Eight patients with CgA levels >150 U/L underwent scintigraphy, five of whom (two colorectal, two prostate, one non-small cell lung cancer [NSCLC]) showed positive results and received treatment with octreotide. Follow up for a mean 12-16 months showed improvements in biochemical parameters, cenesthesis and quality of life. CONCLUSION: CgA levels were found to be elevated in approximately 50% of patients with non-neuroendocrine tumours. Further studies are required to determine the value of CgA as a marker for non-neuroendocrine tumours and the role of somatostatin analogues as a treatment for these tumour types. PMID- 17274679 TI - Role of androgen ablation with low-dose-rate brachytherapy in the treatment of prostate cancer. AB - BACKGROUND: Androgen ablation is often used in addition to low-dose-rate brachytherapy in the treatment of prostate cancer, particularly for disease with adverse features. We report a single-institution experience and analysis of the role of androgen ablation with brachytherapy in patients with prostate cancer. METHODS: A cohort of 189 consecutive patients receiving low-dose-rate brachytherapy for prostate cancer at our institution who had demographic, disease and treatment information and a minimum of 2 years of follow-up available, constituted the analysis study group. This cohort was divided into two major categories based on the use of androgen ablation. Using two successive prostate- specific antigen (PSA) rises above 1 ng/mL as the definition of failure, biochemical failure-free survival (BFFS) curves were constructed for the androgen ablation and no-androgen ablation groups and compared using the log rank test; additionally, a multivariate analysis of all major disease and treatment factors was performed using the Cox proportional hazards model. These analyses were conducted for the whole cohort as well as for subgroups defined by the use of external beam radiotherapy (EBRT). RESULTS: The 4-year BFFS in the androgen ablation versus no-androgen ablation groups was 76% versus 70% (p = 0.230) for the whole cohort, 75% versus 62% (p = 0.182) for EBRT patients, and 75% versus 82% (p = 0.764) for no-EBRT patients. For the whole cohort, the use of EBRT was the only factor reaching significance on multivariate analysis (p = 0.040). When analysing the EBRT and no-EBRT subgroups separately, no factor, including androgen ablation, reached significance on multivariate analysis. CONCLUSION: In our study, addition of androgen ablation conferred no biochemical control advantage when added to low-dose-rate brachytherapy for the treatment of patients with prostate cancer. PMID- 17274680 TI - Real-life treatment of acute exacerbations of chronic bronchitis with moxifloxacin or macrolides: a comparative post-marketing surveillance study in general practice. AB - OBJECTIVE: To compare the real-life treatment of acute exacerbations of chronic bronchitis (AECBs) using moxifloxacin tablets or one of the oral macrolides azithromycin, clarithromycin or roxithromycin in terms of symptom relief, time until improvement and cure, overall efficacy and tolerability. METHODS: This prospective, non-interventional, multicentre study included out-patients with AECB whose last exacerbation was treated with a macrolide. The current AECB was treated either with moxifloxacin or with one of the macrolides azithromycin, clarithromycin or roxithromycin. Data were obtained on the patient's characteristics, disease and treatment history, the course of the current AECB including time to improvement and cure, and the final assessments of efficacy and tolerability. All adverse events were recorded in patients treated with moxifloxacin; for patients receiving macrolides, only drug-related adverse events were reported. RESULTS: 464 physicians treated 904 patients with moxifloxacin and 846 patients with one of the macrolides. Age, sex and body mass index were well matched between the two treatment groups. However, more moxifloxacin than macrolide patients presented with a generally bad condition (62.8% vs 48.6%). About 42% of patients in both groups had had chronic bronchitis for 1-5 years, and about 27% for 5-10 years. The mean number of AECBs in the previous 12 months was 2.7 and 2.6, respectively. Moxifloxacin was administered to most patients for 5 (43.8%) or 7 days (42.4%). Patients in the macrolide group were treated in most cases with clarithromycin 500 mg for 4-7 days, roxithromycin 300 mg for 6-7 days or azithromycin 500 mg for 3 days. Physicians assessed overall efficacy and tolerability as 'very good' or 'good' in 96.1% and 98.1%, respectively, of moxifloxacin-treated patients and in 67.5% and 91.7%, respectively, of macrolide treated patients. The mean duration until improvement and cure of AECB was 3.2 days (+/- SD 1.5) and 6.2 days (+/- 2.6) in moxifloxacin-treated patients compared with 4.5 days (+/- 1.8) and 7.5 days (+/- 3.0) in macrolide-treated patients (p < 0.0001). CONCLUSION: The results of this study conducted under real life treatment conditions in patients with AECBs who were previously treated with a macrolide showed faster symptom relief and higher recovery rates with moxifloxacin compared with macrolides. The two treatment groups had comparably good safety and tolerability profiles. PMID- 17274681 TI - Metoclopramide-induced delayed non-thrombocytopenic purpuric rash. AB - A 62-year-old man with no drug allergies was admitted for coronary artery bypass grafting. Postoperatively, metoclopramide was commenced for the treatment of gastroparesis. Ten days after the drug was initiated a purpuric rash was noticed on his lower limbs. His platelet count was normal. Infection was excluded and the cause was not obvious. No change was noticed in the condition of rash despite discontinuation of all other medications started in the hospital one at a time. The rash later began to subside upon discontinuation of metoclopramide. A rechallenge was not attempted for ethical reasons. In conclusion, metoclopramide was considered to be the causative agent of this rash as it subsided after the discontinuation of metoclopramide. PMID- 17274682 TI - Robustness can evolve gradually in complex regulatory gene networks with varying topology. AB - The topology of cellular circuits (the who-interacts-with-whom) is key to understand their robustness to both mutations and noise. The reason is that many biochemical parameters driving circuit behavior vary extensively and are thus not fine-tuned. Existing work in this area asks to what extent the function of any one given circuit is robust. But is high robustness truly remarkable, or would it be expected for many circuits of similar topology? And how can high robustness come about through gradual Darwinian evolution that changes circuit topology gradually, one interaction at a time? We here ask these questions for a model of transcriptional regulation networks, in which we explore millions of different network topologies. Robustness to mutations and noise are correlated in these networks. They show a skewed distribution, with a very small number of networks being vastly more robust than the rest. All networks that attain a given gene expression state can be organized into a graph whose nodes are networks that differ in their topology. Remarkably, this graph is connected and can be easily traversed by gradual changes of network topologies. Thus, robustness is an evolvable property. This connectedness and evolvability of robust networks may be a general organizational principle of biological networks. In addition, it exists also for RNA and protein structures, and may thus be a general organizational principle of all biological systems. PMID- 17274683 TI - Automatic extraction of protein point mutations using a graph bigram association. AB - Protein point mutations are an essential component of the evolutionary and experimental analysis of protein structure and function. While many manually curated databases attempt to index point mutations, most experimentally generated point mutations and the biological impacts of the changes are described in the peer-reviewed published literature. We describe an application, Mutation GraB (Graph Bigram), that identifies, extracts, and verifies point mutations from biomedical literature. The principal problem of point mutation extraction is to link the point mutation with its associated protein and organism of origin. Our algorithm uses a graph-based bigram traversal to identify these relevant associations and exploits the Swiss-Prot protein database to verify this information. The graph bigram method is different from other models for point mutation extraction in that it incorporates frequency and positional data of all terms in an article to drive the point mutation-protein association. Our method was tested on 589 articles describing point mutations from the G protein-coupled receptor (GPCR), tyrosine kinase, and ion channel protein families. We evaluated our graph bigram metric against a word-proximity metric for term association on datasets of full-text literature in these three different protein families. Our testing shows that the graph bigram metric achieves a higher F-measure for the GPCRs (0.79 versus 0.76), protein tyrosine kinases (0.72 versus 0.69), and ion channel transporters (0.76 versus 0.74). Importantly, in situations where more than one protein can be assigned to a point mutation and disambiguation is required, the graph bigram metric achieves a precision of 0.84 compared with the word distance metric precision of 0.73. We believe the graph bigram search metric to be a significant improvement over previous search metrics for point mutation extraction and to be applicable to text-mining application requiring the association of words. PMID- 17274684 TI - Efficiency and cost of economical brain functional networks. AB - Brain anatomical networks are sparse, complex, and have economical small-world properties. We investigated the efficiency and cost of human brain functional networks measured using functional magnetic resonance imaging (fMRI) in a factorial design: two groups of healthy old (N = 11; mean age = 66.5 years) and healthy young (N = 15; mean age = 24.7 years) volunteers were each scanned twice in a no-task or "resting" state following placebo or a single dose of a dopamine receptor antagonist (sulpiride 400 mg). Functional connectivity between 90 cortical and subcortical regions was estimated by wavelet correlation analysis, in the frequency interval 0.06-0.11 Hz, and thresholded to construct undirected graphs. These brain functional networks were small-world and economical in the sense of providing high global and local efficiency of parallel information processing for low connection cost. Efficiency was reduced disproportionately to cost in older people, and the detrimental effects of age on efficiency were localised to frontal and temporal cortical and subcortical regions. Dopamine antagonism also impaired global and local efficiency of the network, but this effect was differentially localised and did not interact with the effect of age. Brain functional networks have economical small-world properties-supporting efficient parallel information transfer at relatively low cost-which are differently impaired by normal aging and pharmacological blockade of dopamine transmission. PMID- 17274685 TI - Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans. AB - The fungal pathogens Aspergillus fumigatus and Candida albicans are major health threats for immune-compromised patients. Normally, macrophages and neutrophil granulocytes phagocytose inhaled Aspergillus conidia in the two-dimensional (2-D) environment of the alveolar lumen or Candida growing in tissue microabscesses, which are composed of a three-dimensional (3-D) extracellular matrix. However, neither the cellular dynamics, the per-cell efficiency, the outcome of this interaction, nor the environmental impact on this process are known. Live imaging shows that the interaction of phagocytes with Aspergillus or Candida in 2-D liquid cultures or 3-D collagen environments is a dynamic process that includes phagocytosis, dragging, or the mere touching of fungal elements. Neutrophils and alveolar macrophages efficiently phagocytosed or dragged Aspergillus conidia in 2 D, while in 3-D their function was severely impaired. The reverse was found for phagocytosis of Candida. The phagocytosis rate was very low in 2-D, while in 3-D most neutrophils internalized multiple yeasts. In competitive assays, neutrophils primarily incorporated Aspergillus conidia in 2-D and Candida yeasts in 3-D despite frequent touching of the other pathogen. Thus, phagocytes show activity best in the environment where a pathogen is naturally encountered. This could explain why "delocalized" Aspergillus infections such as hematogeneous spread are almost uncontrollable diseases, even in immunocompetent individuals. PMID- 17274686 TI - Antifungal chemical compounds identified using a C. elegans pathogenicity assay. AB - There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi. PMID- 17274687 TI - New small nuclear RNA gene-like transcriptional units as sources of regulatory transcripts. AB - By means of a computer search for upstream promoter elements (distal sequence element and proximal sequence element) typical of small nuclear RNA genes, we have identified in the human genome a number of previously unrecognized, putative transcription units whose predicted products are novel noncoding RNAs with homology to protein-coding genes. By elucidating the function of one of them, we provide evidence for the existence of a sense/antisense-based gene-regulation network where part of the polymerase III transcriptome could control its polymerase II counterpart. PMID- 17274690 TI - Shifting the focus from cost to value: an employer perspective. AB - OBJECTIVE: To review ways in which pharmacists can help health plans shift their focus from cost to value. SUMMARY: Health care delivery is a continuum. Employers have moved along the continuum looking for value; they are now looking for integrated strategies to decrease cost and improve productivity within the workforce. The key to any integrated strategy is innovative service delivery and ground-breaking partnerships with vendors. Key areas that need to be addressed are medical care, pharmacy, behavioral health, disability, prevention, and presenteeism. Additionally, measuring program effectiveness is becoming more important, especially in terms of continuous improvement. CONCLUSION: Updating data, fine-tuning plan design to improve effectiveness, and abandoning ineffective efforts is critical. The ultimate goal is to modify the target population.s risk. PMID- 17274691 TI - Shifting the focus from cost to value: a government perspective. AB - OBJECTIVE: To examine the federal government.s current health care initiatives in the Centers for Medicare and Medicaid Services (CMS) to improve quality of care and cost-effectiveness around the prescription drug benefit. SUMMARY: The government has a unique perspective on quality and outcome. Pharmacists need a working knowledge of 3 areas: (1) Medicare Part D, (2) medication therapy management efforts, and (3) demonstration projects. All of these will make demands on health care providers but should result in better outcomes data and patient care. All of these areas also have value components, and all have strategic implications as 2006 moves into 2007. CONCLUSION: CMS does not consider managing cost and providing value to be mutually exclusive and is attempting to move America.s health care toward a value-based program. PMID- 17274692 TI - Shifting the focus from cost to value: a private payer perspective. AB - OBJECTIVE: To present the issues, concerns, and advances possible as private (commercial) payers attempt to incorporate value into their health care plans, using a commercial provider of disease and medication management as a model. SUMMARY: Most approaches to health care have dealt with persistent or chronic diseases, but, increasingly, payers are expanding their interests to include wellness, high-risk case management, and care management. Technology is crucial in health care today, enabling clinicians to reach out to patients, capture data, and integrate medical and pharmaceutical data. Data integration will help build efficiencies and effective ways to deal with the growing population of patients who have chronic disease. The disease-centric model is being replaced with a patient-centric model. Health care providers must help patients identify their unique motivators and de-motivators and encourage them to be self-sufficient partners in their own health care. CONCLUSION: Adding value to traditional health care is a task that seems daunting at first. It is not insurmountable, however, and ultimately, adding value decreases cost in unprecedented ways. PMID- 17274688 TI - Transition-transversion bias is not universal: a counter example from grasshopper pseudogenes. AB - Comparisons of the DNA sequences of metazoa show an excess of transitional over transversional substitutions. Part of this bias is due to the relatively high rate of mutation of methylated cytosines to thymine. Postmutation processes also introduce a bias, particularly selection for codon-usage bias in coding regions. It is generally assumed, however, that there is a universal bias in favour of transitions over transversions, possibly as a result of the underlying chemistry of mutation. Surprisingly, this underlying trend has been evaluated only in two types of metazoan, namely Drosophila and the Mammalia. Here, we investigate a third group, and find no such bias. We characterize the point substitution spectrum in Podisma pedestris, a grasshopper species with a very large genome. The accumulation of mutations was surveyed in two pseudogene families, nuclear mitochondrial and ribosomal DNA sequences. The cytosine-guanine (CpG) dinucleotides exhibit the high transition frequencies expected of methylated sites. The transition rate at other cytosine residues is significantly lower. After accounting for this methylation effect, there is no significant difference between transition and transversion rates. These results contrast with reports from other taxa and lead us to reject the hypothesis of a universal transition/transversion bias. Instead we suggest fundamental interspecific differences in point substitution processes. PMID- 17274693 TI - The role of outcomes research in defining and measuring value in benefit decisions. AB - OBJECTIVE: To identify ways that health care leaders at all levels can quantify the value proposition, thus influencing health care delivery and improving patient care. SUMMARY: Payers and providers need to support, with rigorous research, the value proposition for customers. Outcomes research focusing on clinical and cost-effectiveness analysis can provide an understanding of successful, replicable interventions. Randomized controlled trials and observational studies can be used to reinforce and refine the business proposition in health care, and they can be integrated to target populations needing health care services. Evaluations using clinical and outcomes research can also predict what is likely to be successful in the future. To maximize the business value of projects, they must incorporate a prospective evaluation component that includes asking the right research questions, identifying an appropriate time period, including a targeted population, articulating a replicable intervention, and determining the correct statistical analysis. CONCLUSION: Well-designed studies to analyze specific patient populations and their patterns of care can be used to determine a generalizable model to refine successful interventions that meet the critical value proposition for employers. PMID- 17274694 TI - Hepatocellular carcinoma and liver transplantation. PMID- 17274695 TI - Survival of patients receiving a liver transplant for hepatocellular carcinoma, and risk of tumor recurrence. AB - OBJECTIVE: The goal of this research has been to evaluate the survival, in long and short term, of the patient receiving liver transplant for hepatocellular carcinoma (HCC), the risk of post-transplant tumor relapse and factors related to this complication. DESIGN: Retrospective study of a consecutive series of patients having had liver transplant for HCC. PATIENTS AND METHODOLOGY: Transplant patients for HCC from 1989 to November 2003. Patients were selected due to general limitations of nodule size and quantity, which were subsequently published as Milan criteria. Also, criteria agreed in the Conference of Barcelona were followed in the pre-transplant diagnosis. RESULTS: The survival of this 81 patients group was of the 80, 61 and 52% for 1, 5 and 10 years respectively. In the 32% of the cases the HCC was an incidental finding in the explant. In the 12.3%, the tumor relapse was verified. The multivariate research identified the size of the nodule (OR=1,7944) (IC 95%=1,1332-2,8413) and the vascular invasion (OR=6,6346) (IC 95%=1,4624-30,1003) as risk factors of relapse. CONCLUSIONS: The liver transplant in selected patients with HCC has good results in medium and long term. The risk of post-transplant tumor relapse becomes notably reduced and is associated with the size of the nodule and the microscopic vascular invasion. PMID- 17274696 TI - Multiple malignant primary neoplasms in patients with gatric neoplasms in the health district of Leon. AB - OBJECTIVES: We analyzed the characteristics of patients with gastric tumors diagnosed with multiple malignant primary neoplasm (MMPN) in the Health District of Leon. MATERIAL AND METHODS: Using the information in the Tumor Registry at Leon Hospital patients selected were those with gastric neoplasms diagnosed between 1993 and 2002. A follow-up was performed until December 31, 2004, and the characteristics of patients diagnosed with a second neoplasm were analyzed. RESULTS: MMPN prevalence was 1,96%; 56% of patients had a history of cancer in first-degree relatives. The most frequent second neoplasms were digestive (26%) and urologic (21%); 87% of patients were diagnosed with a second neoplasm within the first two years. No significative differences in survival were observed among patients with synchronous or metachronous MMPN. CONCLUSIONS: MMPN in patients with gastric neoplasms is a relevant problem. While external carcinogenic agents could act as promoters in the development of second neoplasms, these patients seem to have a genetic background favoring the development of MMPN. Secondary prevention is the best measure to avoid MMPN development. PMID- 17274698 TI - Results of a survey in Andalusian endoscopy units. AB - INTRODUCTION: In Spain, there is no indication of the resources that an endoscopy unit should have. As a consequence only the experience of professionals who have been working for years in this field can be used as a guide. However, there are some recent surveys on sedation in Spain that indicate how sedation is use in other units. OBJECTIVES: The objectives of the present study were: a) to find out the human and material resources available in endoscopy units in Andalusia; b) to analyze the number of endoscopies performed in our country; and c) to identify factors that can be improved. MATERIAL AND METHODS: In order to make an assessment of the conditions and resources of said units in Andalusia, a survey was designed for the staff of gasteroenterology department. Hospitals involved are those specified in this paper. The survey, which included 90 questions, covers all aspects concerning each unit. There are questions on the real conditions of the unit, and on what would be considered as ideal or at least as minimal requirement for each hospital or Health Area. CONCLUSIONS: Even though some shortcomings were found in some hospitals, a high percentage of them have acceptable equipment. However, due to fast advances in the field of endoscopy, an improvement in the conditions should be provided, especially in aspects concerning anesthesia. PMID- 17274697 TI - Ancillary personnel faced with living liver donation in a Spanish hospital with a transplant program. AB - INTRODUCTION: Ancillary hospital personnel represent an important body of opinion because as they work in a hospital their opinion has more credibility for the general public as a result of their activity in hospitals. However, in most cases they do not have any health care training which means that their attitude could be based on a lack of knowledge or unfounded fears. The objective of this study is to analyze the attitude toward living liver donation among ancillary personnel in a hospital with a cadaveric and living liver organ transplant program and to analyze the variables that might influence such attitude. PATIENTS AND METHOD: A random sample was taken which was stratified by service (n=401) among ancillary personnel in the hospital. Attitude was evaluated using a survey that was validated in our geographical area. A representative from each service was contacted. This person was given an explanation of the study and was made responsible for the distribution of the questionnaire in selected work shifts. The survey was completed anonymously and was self-administered. The c2 test, Student s t-test and logistical regression analysis were used in the statistical analysis. RESULTS: The questionnaire completion rate was 94% (n=377). Of all the respondents, 20% (n=74) are in favor of donating a living hemi-liver, but an additional 62% (n=233) are in favor if donation is for a relative. Of the rest, 8% (n=30) do not accept this type of donation and the remaining 11% (n=40) are unsure. The following variables are related to attitude toward living liver donation: attitude toward cadaveric donation (p=0.002); a respondent s belief that he or she might need a transplant in the future (p<0.001) and a willingness to receive a donated living liver if one were needed (p<0.001). In the multivariate analysis the following have been found to be significantly related variables: a) a respondent s belief that he or she might need a transplant in the future (OR=1.5); and b) a willingness to receive a living donated kidney if one were needed (OR=16.2). CONCLUSIONS: Attitude toward living liver donation is fairly favorable among ancillary personnel in a transplant hospital and is not affected by the psychosocial factors found to be related to attitude toward donation in previous studies. However, if we want to encourage this type of transplantation with living donors it will be necessary to carry out informative campaigns to raise awareness within the hospital. PMID- 17274699 TI - Sedation for gastrointestinal endoscopy and intrusionism: legal aspects. PMID- 17274700 TI - Pneumatosis cystoides intestinalis. PMID- 17274701 TI - [Gallbladder agenesia: Diagnosis of a case without surgery]. PMID- 17274702 TI - [Superior mesenteric and celiac trunk ischemia after administration of cocaine]. PMID- 17274703 TI - [Immunohystochemical and prognosis features of adenocarcinoid tumor of the ampulla of Vater]. PMID- 17274704 TI - Supporting rural carers through telehealth. AB - INTRODUCTION: Videoconferencing is now a firmly established feature of rural health care in Australia. However, the health sector has not used videoconferencing extensively outside the provision of clinical care. This article describes a program of education and support to rural carers via videoconferencing which demonstrates its potential in promoting health. METHODS: Semi-structured interviews were conducted with six service providers, eight carers who participated in sessions and the facilitator of the sessions. Attendance and financial records augmented the interview data. RESULTS: Videoconferencing was well accepted by carers and the facilitator. Carers reported having a positive interaction with the facilitator and other participants despite being at a distance, and the facilitator found the technology offered her more ways to observe non-verbal cues discretely. Carers demonstrated that they had retained information provided and that they had made small behaviour changes. They credited the success to sharing experiences with peers. Local providers of aged care services stressed that the sessions offered a service that they, who were employed to be 'problem-solvers', were not able to perform but that as a result of the sessions they could target services more effectively. Videoconferenced sessions were 16% and 47% of the cost of a face-to face session. CONCLUSIONS: This study demonstrates that videoconferencing can be used to provide psychosocial support and training to groups of isolated carers. The critical element of this program was that local services were augmented and enhanced through the use of a facilitator who brought skills that were not available locally. PMID- 17274705 TI - Has periodontal treatment failed to reduce adverse pregnancy outcomes? The answer may be premature. PMID- 17274706 TI - Periodontal disease progression among young subjects with no preventive dental care: a 52-month follow-up study. AB - BACKGROUND: The aim of the present study was to assess the incidence, severity, and extension of periodontal disease among young subjects. METHODS: Three hundred sixty subjects from a public school in Belo Horizonte, Brazil were examined. Forty-four subjects with bone loss (BL) and/or clinical attachment loss (CAL) > or = 4 mm, and no dental care during the following 52 months, were considered the reference sample and were recalled for a second examination. At both examinations, statistical analyses were performed for CAL and BL for subject, tooth, and site. Comparisons of CAL at subject, tooth, and site levels were performed with the Wilcoxon test for matched samples. Comparisons of BL at subject, tooth, and site levels were performed with the McNemar and Student t tests for dependent samples. RESULTS: Findings indicated an increase in the number of sites with CAL >4 mm from baseline to follow-up. Sites that exhibited BL increased from 2.14% at baseline to 7.5% at follow-up (P <0.001). The severity of periodontitis was characterized by increased CAL values at affected sites at both examinations (P <0.001) and an increase in BL over time (mean BL at 35 affected sites was 2.6 mm at baseline and 3.5 mm at follow-up; P = 0.001). In addition, a 34% incidence of BL was verified. CONCLUSIONS: The incidence, severity, and extension of CAL and BL were significant findings. They indicate the importance of early detection of the disease and the need for preventive health care programs geared toward young subjects. PMID- 17274707 TI - Peri-implant bone loss around posterior mandible dental implants placed after distraction osteogenesis: preliminary findings. AB - BACKGROUND: The present study evaluates implant survival and peri-implant bone loss around posterior mandible dental implants placed at sites of distraction osteogenesis. METHODS: On removal of the distraction devices, 34 dental implants were inserted into 14 posterior mandible sites in 10 healthy, non-smoking female patients. Prosthetic treatment was performed 4 months after implant placement using fixed implant prostheses. After 6 to 16.5 months, periapical radiographs were taken and evaluated for peri-implant bone loss and radiolucency. The distance between the implant margin and the first visible bone-implant contact was measured on the mesial and distal aspects of the implants using imaging software. Radiographic dimensional distortion was corrected as a function of the known true dimension of the implant. RESULTS: Of the 34 implants placed, two (5.9%) failed to integrate at reentry surgery. Both were replaced and restored during the course of the study so that a total of 34 implants was followed for 12.1 +/- 3.8 months post-restoration and 16.1 +/- 3.8 months post-insertion. Mean loss of marginal bone height was 2.6 +/- 1.0 mm. During the follow-up period, radiolucent lines along the implant surface were absent. CONCLUSIONS: The mean peri-implant bone loss in areas of alveolar bone distraction was 1.9 mm/year. A high implant survival rate was observed. PMID- 17274708 TI - Randomized, controlled histologic and histomorphometric evaluation of implants with nanometer-scale calcium phosphate added to the dual acid-etched surface in the human posterior maxilla. AB - BACKGROUND: Placement of dental implants in the posterior maxilla has been associated with higher rates of failure that are due, in part, to the poor bone quality of this region. The purpose of the present study was the histologic and histomorphometric evaluation of the bone around a new implant surface treatment created by a deposition of nanometer-sized calcium phosphate particles added to the dual acid-etched surface. METHODS: One custom-made 2 x 10-mm site evaluation implant (SEI) with this novel treatment surface (test) and one SEI with the dual acid-etched surface without treatment (control) were placed in the posterior maxilla of 15 patients. All SEIs were retrieved after 2 months and evaluated under confocal laser scanning microscopy (CLSM) and by light microscopy for histomorphometric analysis of the bone-implant contact (BIC). RESULTS: Histologic observations in control SEIs showed formation of new bone around the implant surface; however, it was not always in direct contact with the entire perimeter of the threads. The mean BIC was 19% +/- 14.2%. Test SEIs showed peri-implant bone tightly contacting the implant surface and better adapted to the threads. Three-dimensional reconstruction of sections obtained using CLSM showed the intimacy of the contact between bone and test SEI surface through the entire thickness of the specimens. The mean BIC was 32.2% +/- 18.5%. CONCLUSIONS: After 2 months of healing, comparison of the BIC values showed a statistically significant greater mean BIC for test SEIs than for controls. The clinical implications of these results included shortening of the implant healing period and earlier loading protocols. PMID- 17274709 TI - Survival of immediately provisionalized dental implants placed immediately into fresh extraction sockets. AB - BACKGROUND: The aim of this study was to evaluate the survival rate of immediately provisionalized dental implants immediately placed into fresh extraction sockets. METHODS: The study consisted of 87 consecutive patients, ranging in age from 21 to 76 years (average: 53.30 +/- 13.34 years), who received 210 immediately provisionalized, immediately placed dental implants between the years 2000 and 2005. Data were recorded regarding the survival rate of these implants and the incidence of complications. RESULTS: Follow-up ranged from 6 to 52 months (mean: 15.60 +/- 12.60 months). Smoking, past and present, was reported by 28.7% and 20.7% of patients, respectively. The maxillary incisors were replaced most frequently, followed by the mandibular lateral incisors. Most of the implants were >13 mm in length and > or = 3.75 mm in diameter. There were 47 (22.4%) single restored implants and 163 (77.6%) splinted implants. Overall, the implant survival rate was 97.6% (five implants failed). Complications, such as swelling, inflammation, and pain, were observed in 24 (11.4%) of the implants. No relation was found between complications and failure. The present study failed to reveal a relationship between implant survival rate and smoking, implant dimensions, and area of implantation. CONCLUSION: Immediately provisionalized immediate implants can serve as a predictable procedure with high survival rates. PMID- 17274710 TI - Comparative study of ultrasonic instrumentation for the non-surgical treatment of interproximal and non-interproximal furcation involvements. AB - BACKGROUND: The aim of this clinical trial was to compare the outcome of non surgical treatment of interproximal and non-interproximal Class II furcation involvements. METHODS: Thirty-eight patients presenting at least one Class II furcation involvement that bled on probing with a probing depth (PD) > or = 5 mm were recruited. Furcation involvements were grouped as either buccal and lingual furcation involvements (BLFI) or interproximal furcation involvements (IFI). The following clinical outcomes were evaluated: visible plaque index, bleeding on probing (BOP), position of the gingival margin, relative attachment level (RAL), PD, and relative horizontal attachment level (RHAL). N-benzoyl-l-arginine-p nitroanilide (BAPNA) testing was used to analyze trypsin-like activity in dental biofilm. All parameters were evaluated at baseline and 1, 3, and 6 months after non-surgical subgingival instrumentation. RESULTS: Six months after treatment, both groups had similar means of RAL and RHAL gain (P >0.05). These variables were 1.22 and 1.07 mm in the IFI group and 1.38 and 1.20 mm in the BLFI group, respectively. The PD reduction was significantly greater in the BLFI group than in the IFI group (2.59 and 2.11 mm, respectively; P <0.05). The BLFI group presented fewer sites with PD > or = 5 mm than the IFI group at all post treatment periods. At 6 months, the BAPNA test showed that only the BLFI group had values significantly different from baseline. This means that the BLFI group had significantly lower BAPNA values compared to the IFI group at 6 months. CONCLUSION: Buccal and lingual Class II furcation involvements respond better to non-surgical therapy compared to interproximal Class II furcation involvements. PMID- 17274711 TI - Effect of autogenous cortical bone particulate in conjunction with enamel matrix derivative in the treatment of periodontal intraosseous defects. AB - BACKGROUND: The aim of the present study was to assess the additional clinical benefit of autogenous cortical bone particulate (ACBP) when added to enamel matrix derivative (EMD), compared to EMD alone, in the treatment of deep periodontal intraosseous defects. METHODS: A total of 28 intraosseous lesions in 27 patients with advanced periodontitis were included in this controlled clinical trial and randomly assigned to the EMD group (14 defects) or to the EMD + ACBP group (14 defects). Immediately before surgery (baseline) and after 6 and 12 months, probing depth (PD), clinical attachment level (CAL), and gingival recession (REC) were recorded. Radiographic depth of the defect (DEPTH) was also measured at baseline and 12 months post-surgery. RESULTS: At 6 and 12 months, PD and CAL significantly improved from baseline in both groups (P <0.000). No significant differences in terms of CAL gain and PD reduction were detected between groups. However, defect distribution according to CAL gain was significantly different between groups (P <0.05). DEPTH significantly decreased from baseline to 12 months in both groups (P <0.000); between-group differences were not significant. At 12 months, a significantly greater REC increase in the EMD group (1.1 +/- 0.7 mm) compared to the EMD + ACBP group (0.3 +/- 0.8 mm) was observed (P <0.05). CONCLUSIONS: Both EMD and EMD + ACBP treatments led to a significant improvement in clinical and radiographic parameters at follow-up with respect to presurgery condition. The combined approach resulted in reduced post surgery recession and increased proportion of defects with substantial CAL gain (> or = 6 mm). PMID- 17274712 TI - Assessment of pain associated with the surgical placement of dental implants. AB - BACKGROUND: Despite increasing popularity and established predictability, limited information is available on the pain experience associated with the surgical placement of dental implants. The aim of this study was to assess patient reported pain during and after implant insertion and to evaluate factors associated with this pain. METHODS: This was a prospective, two-center study of adult patients scheduled for the surgical placement of one or more implants. Surgery was performed by an experienced periodontist or periodontal graduate students. Mean pain scores were evaluated with the use of a 0 to 10 scale during surgery and 24 hours and 1, 6, and 12 weeks after surgery and compared between the two centers. The association of pain scores at each time-point with patient-, operator-, and surgery-related factors was examined through univariate and multiple logistic regression analyses. RESULTS: Five hundred ten implants were placed in 234 patients during the study. Mean pain scores were highest at 24 hours after surgery (2.01 +/- 0.11) and decreased gradually thereafter. Pain intensity was mild for the majority of patients at all time-points, and only a few patients had moderate or severe pain. Regression analysis revealed that factors significantly associated with pain after 24 hours included operator experience (odds ratio [OR] = 24.86), pain during surgery (OR = 2.81), and female gender (OR = 2.51). After 1 week, pain levels were associated significantly with having pain after 24 hours (OR = 38.69) and having a surgical template used during surgery (OR = 1.11). CONCLUSIONS: Pain experienced by patients following the surgical placement of dental implants was generally mild and gradually decreased with time. Operator experience, female gender, surgical difficulty, and pain at earlier time-points were associated significantly with patient reports of pain. PMID- 17274713 TI - Hemostatic and anesthetic efficacy of 4% articaine HCl with 1:200,000 epinephrine and 4% articaine HCl with 1:100,000 epinephrine when administered intraorally for periodontal surgery. AB - BACKGROUND: The objective of this double-masked, randomized, multicenter crossover study was to compare the efficacy of 4% articaine HCl with 1:100,000 epinephrine (A100) to 4% articaine HCl with 1:200,000 epinephrine (A200) for providing effective local anesthesia and hemostasis for periodontal surgery. METHODS: Anesthetic efficacy was based on patient self-report and lack of need for reinjection during the surgical procedures. Hemostatic properties of the formulations were compared using ratings of the surgeons' ability to visualize the surgical field and expectation for bleeding. The volume of blood collected during each surgical session also was measured and compared. RESULTS: Forty-two adult subjects (26 males and 16 females, mean age 46.3 +/- 9.7 years) diagnosed with moderate to severe periodontal disease requiring local anesthesia for matched bilateral periodontal surgery were enrolled and completed the study. Subjects reported satisfactory surgical anesthesia following the A100 and A200 formulations; no supplemental local anesthesia was administered. Significant differences between the A100 and A200 treatments were found for the surgeons' ability to visualize the surgical field (rated as clear 83.3% of the time with A100 and 59.5% of the time with A200; P = 0.008), bleeding expectation (rated as equal to or better than expected 85.7% of the time with A100 and 71.4% of the time with A200; P = 0.034), and volume of blood loss (54.9 +/- 36.0 ml for A100 and 70.2 +/- 53.0 ml for A200; P = 0.018). Sixteen patients experienced 27 mild or moderate adverse events; the most common were postoperative pain (nine patients) and swelling (eight patients). Six adverse events may have been related to treatment. The frequency of adverse events did not vary between formulations. CONCLUSIONS: For patients undergoing periodontal surgery, 4% articaine anesthetic formulations containing epinephrine (1:100,000 or 1:200,000) provided excellent surgical pain control. For patients who can tolerate higher amounts of epinephrine, the 4% articaine 1:100,000 epinephrine formulation had the additional therapeutic advantage of providing better visualization of the surgical field and less bleeding. PMID- 17274714 TI - Demographic, pharmacologic, and periodontal variables for gingival overgrowth in subjects medicated with cyclosporin in the absence of calcium channel blockers. AB - BACKGROUND: The role of cyclosporin in the absence of calcium channel blockers and the associated risk variables of development and severity of gingival overgrowth have not yet been properly established. The present study was conducted to determine the effect of potential risk variables for gingival overgrowth severity in Brazilian renal transplant subjects medicated with cyclosporin in the absence of any calcium channel blockers. METHODS: A cross sectional study was conducted in a public hospital in Belo Horizonte, Brazil. Demographic, pharmacologic, and periodontal data, recorded from 194 subjects taking cyclosporin in the absence of calcium channel blockers, were analyzed using independent sample t, chi2 statistic, or Mann-Whitney U tests. The effects of potential risk variables of gingival overgrowth severity were determined using backward stepwise regression analysis. RESULTS: The prevalence of clinically significant gingival overgrowth was 34.5% (N = 67). These subjects presented a significantly higher papillary bleeding index and a higher plaque index compared to those without clinically significant gingival overgrowth. When all demographic, pharmacologic, and periodontal data were evaluated in relation to gingival overgrowth severity, time since transplant, papillary bleeding index, serum cyclosporin concentration, and prednisolone and azathioprine dosages were significant in the univariate modeling (P <0.05) and remained significant when evaluated in the multivariate modeling (P <0.0001; adjusted R2 = 39.4%). CONCLUSIONS: In the absence of calcium channel blockers, this study showed that pharmacologic variables, such as cyclosporin serum concentration, prednisolone and azathioprine dosages, and time since transplant, are strongly related to gingival overgrowth. In addition, the periodontal variable papillary bleeding index highlighted the primary role of inflammation on the pathogenesis and severity of gingival overgrowth. PMID- 17274715 TI - Evaluation of two different resonance frequency devices to detect implant stability: a clinical trial. AB - BACKGROUND: Resonance frequency analysis (RFA) provides a non-invasive assessment of implant stability. The established RFA device uses electronic technology, whereas a recently developed device uses magnetic technology. The goal of this clinical trial was to evaluate the ability of the magnetic RFA device to detect changes in stability during early healing following implant placement and to determine whether the implant stability quotient (ISQ) values obtained correlated with those made with the electronic device. METHODS: RFA assessments were performed using electronic- and magnetic-based devices on 34 non-submerged titanium dental implants in 17 patients. Each patient received two implants in the posterior maxilla or mandible. Implant stability was measured at placement and weekly until week 6, when implants received provisional crowns, and at 12 weeks, when definitive crowns were cemented. During each visit, measurements were taken three times and averaged to obtain a single representative ISQ for each device. RESULTS: At placement, the mean ISQ obtained with the electronic device was 61.9 (95% confidence interval [CI], 59.4 to 64.3); it increased to 63.2 (95% CI, 61.2 to 65.2) at 12 weeks. With the magnetic device, the mean ISQs were 70.6 (95% CI, 68.4 to 72.8) and 75.9 (95% CI, 74.2 to 77.7), respectively. Both devices indicated a pattern of decreased mean stability from 1 to 3 weeks post placement, small fluctuations in mean ISQ from 3 to 6 weeks, and significantly increased mean stability from 6 to 12 weeks. For the complete set of implant measures across all weeks, the paired electronic and magnetic ISQ values correlated significantly (r = 0.52; P <0.001). CONCLUSIONS: This study demonstrates that changes in implant stability measured with the newer magnetic device correlate well with those found with the electronic device. Both devices confirmed the initial decreases in implant stability that occur following placement and identified an increase in stability during the first 6 weeks of functional loading. PMID- 17274716 TI - Three-dimensional micro-computed tomographic imaging of alveolar bone in experimental bone loss or repair. AB - BACKGROUND: Micro-computed tomography (micro-CT) offers significant potential for identifying mineralized structures. However, three-dimensional (3-D) micro-CT of alveolar bone has not been adapted readily for quantification. Moreover, conventional methods are not highly sensitive for analyzing bone loss or bone gain following periodontal disease or reconstructive therapy. The objective of this investigation was to develop a micro-CT methodology for quantifying tooth supporting alveolar bone in 3-D following experimental preclinical situations of periodontitis or reconstructive therapy. METHODS: Experimental in vivo bone loss or regeneration situations were developed to validate the micro-CT imaging techniques. Twenty mature Sprague-Dawley rats were divided into two groups: bone loss (Porphyromonas gingivalis lipopolysaccharide-mediated bone resorption) and regenerative therapy. Micro-CT and software digitized specimens were reconstructed three-dimensionally for linear and volumetric parameter assessment of alveolar bone (linear bone height, bone volume, bone volume fraction, bone mineral content, and bone mineral density). Intra- and interexaminer reproducibility and reliability were compared for methodology validation. RESULTS: The results demonstrated high examiner reproducibility for linear and volumetric parameters with high intraclass correlation coefficient (ICC) and coefficient of variation (CV). The ICC showed that the methodology was highly reliable and reproducible (ICC >0.99; 95% confidence interval, 0.937 to 1.000; CV <1.5%), suggesting that 3-D measurements may provide better alveolar bone analysis than conventional 2-D methods. CONCLUSIONS: The developed methods allow for highly accurate and reproducible static measurements of tooth-supporting alveolar bone following preclinical situations of bone destruction or regeneration. Future investigations should focus on using in vivo micro-CT imaging for real-time assessments of alveolar bone changes. PMID- 17274717 TI - Immunohistochemical evaluation of Ki-67 expression and apoptosis in cyclosporin A induced gingival overgrowth. AB - BACKGROUND: This study was planned to evaluate cell division rate and apoptosis by immunohistochemical and in situ hybridization techniques in cyclosporin A (CsA)-induced gingival overgrowth tissue samples to determine whether these processes played a role in the pathogenesis of this condition. METHODS: Fourteen CsA-induced overgrowth tissues from renal transplant recipients, 10 control tissues from patients with plaque-induced gingivitis, and 14 control tissues from systemically and periodontally healthy subjects were evaluated. In patient groups, clinical periodontal recordings and tissue sampling were performed before initiation of any periodontal intervention. Numbers of Ki-67-positive cells/field and apoptotic cells/field in formalin-fixed/paraffin-embedded tissue sections were determined. Data were evaluated by one-way analysis of variance, post hoc Sidak test with modified Bonferroni correction, and Pearson correlation analysis. Three phenytoin- and five nifedipine-induced overgrowth tissues were also processed in the same way, and findings in these tissue specimens were evaluated as case series. RESULTS: The number of keratinocytes was significantly greater in the CsA-induced gingival overgrowth group than in the healthy control group (P <0.05). Cells labeled by in situ end labeling, namely the apoptotic cells, were significantly fewer in the CsA group than in the gingivitis and healthy control groups (P <0.01). Overall, statistically significant positive correlations were found between the numbers of Ki-67-positive cells and probing depth and hyperplastic, bleeding, and plaque indices (P <0.01). Phenytoin and nifedipine samples exhibited obviously higher expression of Ki-67-positive cells than the CsA, gingivitis, and healthy control groups. CONCLUSION: Our findings suggest that decreased apoptosis may have a more prominent role than increased cell division in the pathogenesis of CsA-induced gingival overgrowth. PMID- 17274718 TI - Endothelin-1 and its receptors ET(A) and ET(B) in drug-induced gingival overgrowth. AB - BACKGROUND: The purpose of this study was to study the expression of endothelin-1 (ET-1) and its receptors ETA and ETB in normal human gingiva and cyclosporin induced gingival fibroblasts. METHODS: Gingival samples were collected from eight normal healthy individuals, eight patients with periodontitis, and eight patients with cyclosporin A (CsA)-induced gingival overgrowth. Total RNA was extracted from tissue samples, and reverse transcriptase-polymerase chain reaction was performed for ET-1, ETA, and ETB. ET-1 protein was estimated from the tissues by enzyme-linked immunosorbent assay. The expression of ET-1 and its receptors was also examined in gingival fibroblast cells treated with CsA. RESULTS: ET-1 mRNA expression was significantly higher in patients with CsA-induced gingival overgrowth (P <0.001) than in patients with periodontitis and the controls. ETA mRNA was expressed more than the ETB in all examined samples. In human gingival fibroblasts, ET-1 expression was increased with CsA incorporation compared to controls (P <0.001). CONCLUSION: These results suggest that CsA can modulate the expression of ET-1 in gingival fibroblasts and CsA-induced gingival overgrowth. PMID- 17274719 TI - Effect of in vitro gingival fibroblast seeding on the in vivo incorporation of acellular dermal matrix allografts in dogs. AB - BACKGROUND: Acellular dermal matrix allograft (ADMA) has been used in various periodontal procedures with successful results. Because ADMA has no blood vessels or cells, slower healing and incorporation are observed compared to a subepithelial connective tissue graft. Fibroblasts accelerate the healing process by regulation of matrix deposition and synthesis of a variety of growth factors. Thus, the objective of this study was to evaluate histologically if gingival fibroblasts affect healing and incorporation of ADMA in dogs when used as a subepithelial allograft. METHODS: Gingival fibroblasts were established from explant culture from the connective tissue of keratinized gingiva collected from the maxilla of seven mongrel dogs. ADMA was seeded with gingival fibroblasts and transferred to dogs. Surgery was performed bilaterally, and the regions were divided into two groups: ADMA+F (ADMA containing fibroblasts) and ADMA (ADMA only). Biopsies were performed after 2, 4, and 8 weeks of healing. RESULTS: The quantity of blood vessels was significantly higher in the ADMA+F group at 2 weeks of healing (Kruskal-Wallis; P <0.05). There was no statistical difference (P >0.05) in the number of cell layers, epithelial area, or inflammatory infiltrate between the two groups at any stage of healing. CONCLUSION: The enhanced vascularization in vivo in early stages supports the important role of fibroblasts in improving graft performance and wound healing of cultured graft substitutes. PMID- 17274720 TI - Distinctive molecular composition of human gingival interdental papilla. AB - BACKGROUND: Gingiva is composed of attached and marginal (free) gingiva and interdental papilla. Increasing esthetic demands in dentistry have created a need to restore all parts of the gingiva. However, the interdental papilla has limited regeneration potential compared to other parts of the gingiva. It also is more susceptible to gingival overgrowth, suggesting that it has distinct cellular and molecular properties from other parts of the gingiva. Very little is known about the possible differences in the molecular composition of different parts of the gingiva. METHODS: We compared the expression of a set of key molecules in interdental papilla and marginal gingiva from seven healthy subjects by immunohistochemical staining. RESULTS: In the interdental papilla, immunoreactivity for integrin alphavbeta6 and cytokeratin 19 in the oral epithelium was significantly higher than in marginal gingiva. Expression of type I procollagen, extra domain A (EDA) and extra domain B (EDB) fibronectin isoforms, tenascin-C, transforming growth factor-beta (TGF-beta), connective tissue growth factor (CTGF), and the signaling molecule son-of-sevenless (SOS)-1 also were increased in the interdental papilla. The expression of small leucine rich proteoglycans decorin, biglycan, fibromodulin, and lumican in the interdental papilla was partially different from the marginal gingiva. CONCLUSIONS: Molecular composition of the interdental papilla is distinct from marginal gingiva. Increased expression of molecules normally induced in wound healing (alphavbeta6 integrin, fibronectin-EDB and -EDA, tenascin-C, type I procollagen, TGF-beta, CTGF, and SOS-1) suggests that the cells in the interdental papilla are in an activated state and/or inherently display a specific phenotype resembling wound healing. PMID- 17274721 TI - The use of porous beta-tricalcium phosphate blocks with platelet-rich plasma as an onlay bone graft biomaterial. AB - BACKGROUND: An experimental study of rabbit calvaria evaluated the suitability of porous beta-tricalcium phosphate (beta-TCP) block as a biomaterial for onlay bone grafting and determined whether the addition of platelet-rich plasma (PRP) can accelerate bone formation inside the pores of the beta-TCP block. METHODS: In eight rabbits, the calvarium was exposed, and the marrow was penetrated. The beta TCP blocks were made of Ca3(CO4)3 (porosity, 75%; diameter, 8 mm; thickness, 5 mm). For the experimental group, the blocks were treated with PRP; for the control group, the blocks were treated with venous blood only. Each block was placed in the bone, attached with a titanium screw, and covered with a cutaneous flap. The animals were sacrificed after 3 months, and the tissue ingrowth into the blocks was euthanized. RESULTS: Histologic and histomorphometric measurements demonstrated that there was no inflammatory infiltration around the blocks in either group. New bone formation inside the blocks originated from the parent bone in both groups. The mineralized bone generated tended to climb along the inner walls of the block. In addition, mineralized bone formation was noted around the titanium screw. Furthermore, there was no significant difference between the experimental and control groups in the relative amounts of newly generated tissue and mineralized bone generated in the blocks. CONCLUSION: Porous beta-TCP block is a promising biomaterial for clinical situations requiring bone augmentation; however, the addition of PRP did not induce significantly more new bone formation. PMID- 17274722 TI - Evaluation of the incidence of periodontitis-associated bacteria in the atherosclerotic plaque of coronary blood vessels. AB - BACKGROUND: Unstable atherosclerotic plaque is a dangerous clinical condition, possibly leading to acute coronary deficiency resulting in cardiac infarction. Questions about the role of inflammatory factors in the formation of pathological lesions in the endothelium of coronary vessels have often been raised. This condition may be caused by bacteria that are able to initiate clot formation in a blood vessel, destabilizing an atherosclerotic plaque that is already present. The sources of these pathogens are chronic inflammatory processes occurring in the host, including periodontal disease, which is one of the most frequent conditions. The aim of this study was to evaluate the incidence of selected anaerobic bacteria in subgingival and atherosclerotic plaque in patients treated surgically because of coronary vessel obliteration. METHODS: The study was performed on 20 individuals with chronic periodontitis. Subgingival plaque was collected from periodontal pockets >5 mm. DNA testing was used to identify eight pathogens responsible for periodontal tissue destruction. Material from atherosclerotic plaques was collected from the same patients during bypass surgery, and DNA testing by the same method was performed. RESULTS: In 13 of 20 patients, the pathogens most frequently found in severe chronic periodontitis were also found in coronary vessels. In 10 cases, those species of bacteria were also present in atherosclerotic plaque. The most frequently identified bacteria were Porphyromonas gingivalis and Treponema denticola. CONCLUSIONS: In patients with the severe form of chronic periodontitis, it seems that clinical attachment loss is not associated with bacterial permeability into coronary vessels. What is important is the presence of an active inflammatory process expressed by a significantly higher bleeding index in those patients in whom the examined bacterial species were found in atherosclerotic plaque. PMID- 17274723 TI - Extracellular signal-regulated kinase 1/2 is involved in ascorbic acid-induced osteoblastic differentiation in periodontal ligament cells. AB - BACKGROUND: Periodontal ligament (PDL) cells possess osteoblast-like properties and play key roles in periodontal regeneration. Previously, we have reported that ascorbic acid promotes the osteoblastic differentiation of PDL cells by modulating the type I collagen-integrin interaction. However, the signaling pathway activated following collagen-integrin interaction is still unclear. In this study, we examined the involvement of extracellular signal-regulated kinase (ERK)1/2 in the expression of osteoblastic marker genes such as the osteoblast specific transcriptional factor runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteocalcin (OCN) in PDL cells. METHODS: PDL cells were cultured on a conventional or type I collagen-coated dish in the presence or absence of ascorbic acid and examined for ALP activity and osteoblastic marker genes. For detection of ERK1/2, cells were plated on a petri (non-adhesive) dish or type I collagen-coated dish, and Western blot analysis was performed. The effect of the ERK1/2 inhibitor on osteoblastic marker gene expression was examined. RESULTS: Ascorbic acid increased gene expression of Runx2, ALP, and OCN. A combination of ascorbic acid and type I collagen remarkably upregulated Runx2, ALP, and OCN gene expression and ALP activity. Western blot analysis revealed an increased level of ERK1/2 phosphorylation in cells plated on type I collagen. An ERK1/2 inhibitor suppressed ascorbic acid induced ALP and OCN gene expression, whereas Runx2 was not affected in PDL cells. CONCLUSION: These results indicate that ERK1/2 is involved in ascorbic acid induced osteoblastic differentiation during PDL cell attachment to type I collagen. PMID- 17274725 TI - Tannerella forsythensis prtH genotype and association with periodontal status. AB - BACKGROUND: The prtH gene of Tannerella forsythensis encodes for a cysteine protease possessing virulent properties. Subgingival colonization by T. forsythensis with this genotype has been suggested to be a discriminator between periodontal health and disease. This study examined the prevalence of T. forsythensis prtH genotype in subgingival plaque and its association with periodontal disease progression and current disease status. METHODS: Subjects harboring T. forsythensis in their subgingival plaque were identified using real time polymerase chain reaction (PCR). The presence or absence of the prtH genotype was assessed by conventional PCR. Probing depths and relative attachment levels were also assessed. RESULTS: The prtH genotype was detected in 13 of 56 (23.2%) subjects harboring T. forsythensis in their subgingival plaque. Periodontal disease progression was defined as two or more sites with > or = 2 mm attachment loss in the previous 2-year period; current disease was defined as four or more sites with probing depths > or = 4 mm. The odds of periodontal disease (progression and/or current disease) were 1.55 times greater in subjects harboring prtH genotype T. forsythensis than in subjects in whom prtH was not detected. The prtH genotype was associated with higher numbers of T. forsythensis. In subjects with high levels of T. forsythensis, prtH genotype was associated with an increased extent of periodontal disease 2 years subsequently. CONCLUSIONS: These results show that T. forsythensis prtH genotype is associated with high levels of T. forsythensis. However, further work is needed to determine whether it also is a useful marker of periodontal disease progression in T. forsythensis-infected subjects. PMID- 17274724 TI - Tissue engineering bone formation in novel recombinant human bone morphogenic protein 2-atelocollagen composite scaffolds. AB - BACKGROUND: Bone morphogenic proteins (BMPs) are important bone-induction factors, and the development of a suitable carrier for BMPs is a critical step to achieve osteoinductive function. The aims of the present study were to evaluate, at the cellular and molecular levels, the feasibility of recombinant human BMP-2 (rhBMP-2)-collagen composite scaffold and its efficiency for carrying BMP-2 in ectopic bone formation in rats. METHODS: Scaffolds with (test) or without rhBMP-2 (control) were made and implanted into the calf muscle of 16 5-week-old rats. The tissue responses to the scaffolds were examined by histology. Masson's trichrome and von Kossa stainings were performed to examine collagen matrix deposition and calcification at 3, 7, 10, and 14 days. Expressions of bone phenotypic markers, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein were detected by reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS: No detectable adverse responses were noted around the implanted scaffolds, and the area of the resorbed scaffold had been replaced by young connective tissue by 3 to 7 days in both groups. In the rhBMP-2 composite scaffold, collagen matrix deposition was found in the implanted site on day 7 and initial signs of endochondral differentiation also appeared. Mineralization and the expressions of key bone proteins were demonstrated in chondroblasts and osteoblasts at 7 to 14 days. Molecular cascades of bone induction were not shown in control specimens. CONCLUSION: The rhBMP-2 atelocollagen scaffold showed excellent biocompatibility and possessed a bone inducing capacity in rat within 2 weeks, and, thus, may provide a potential application in tissue engineering of bone tissue. PMID- 17274726 TI - Tobacco as a risk factor for survival of dental implants. AB - BACKGROUND: It has been shown that smoking habits represent an increased risk for impaired bone healing and implant failure. This study aimed to evaluate the implant survival rates among non-smokers (NS) and different kinds of smokers (S). METHODS: A retrospective analysis was made over a 5-year period of the clinical and radiographic findings corresponding to 66 consecutive patients who had received a total of 165 dental implants. Patients were divided into two groups: S, 40 patients (95 implants; 58% of the sample); and NS, 26 patients (70 implants; 42% of the sample). Also, S and NS were classified into four different categories according to daily tobacco use: NS, 26 patients and 70 implants; light smokers (LS), 23 patients and 44 implants; moderate smokers (MS), 11 patients and 25 implants; and heavy smokers (HS), six patients and 26 implants. RESULTS: Sixteen implants (9.7%) failed and had to be removed. Group S showed 15 failures and a success rate of 84.2%. Group NS had only one failure, giving a success rate of 98.6%. The risk of implant failure was approximately 31% in those who smoked more than 20 cigarettes per day. HS showed statistical differences from NS or LS. However, they did not show any differences from MS. CONCLUSIONS: Within the limits of the present study, the use of tobacco involves a 15.8% risk of implant failure, with a 13.1 odds ratio. LS or MS tobacco use involves a 10.1% relative risk of implant loss, whereas the consumption of >20 cigarettes per day increases this risk to 30.8%. PMID- 17274727 TI - Alveolar distraction osteogenesis for bone augmentation of severely atrophic ridges in 10 consecutive cases: a histologic and histomorphometric study. AB - BACKGROUND: This study analyzed bone healing in surgically osteodistracted maxillary and mandibular ridges histologically and histomorphometrically at two different times to determine the best time to insert dental implants. METHODS: Ten consecutive patients with severe maxillary (two patients) or mandibular (eight patients) atrophy underwent surgical osteodistraction with an extraosseous distractor. Seven days after the surgery, the distractor was activated at a rate of 1 mm/day until achieving the planned bone lengthening. The distractor was removed after a consolidation period of 70 days. Bone biopsies were obtained at implant insertion: 70 days after the end of distraction on the day of distractor removal in six patients (group A) or 180 days afterwards in four patients (group B). The biopsies were evaluated histologically and histomorphometrically to measure the osteocyte lacunar area (OLA). RESULTS: The histologic and histomorphometrical analysis of the distracted bone 70 days after the end of distraction showed well-organized lamellar bone. At 180 days, the bone was more compact and mature; the mineralization of the matrix was greater; and an increased, but small, amount of marrow space was evident (35% versus 45%). The mean OLA was 80.11 +/- 27.59 microm2 in group A and 70.4 +/- 33.58 microm2 in group B. The difference between the two biopsy groups was not significant (P = 0.315). CONCLUSION: The results of this study showed that there was definitely similar bone formation in the distracted area for both healing periods, and placing implants clinically worked in both of these time periods in the limited number of cases observed. PMID- 17274728 TI - A familial pattern of multiple idiopathic cervical root resorption in a father and son: a 22-year follow-up. AB - BACKGROUND: The etiology of idiopathic cervical root resorption has not been elucidated clearly. However, the process has been linked to trauma, intracanal bleaching, and partial-thickness connective tissue grafts. METHODS: This study describes a familial pattern of multiple idiopathic cervical root resorption in a father and son. RESULTS: The father was a healthy 63-year-old white male who presented with the first resorption lesion in 1983. Twenty-seven additional lesions were identified on 16 teeth over 22 years. Five teeth were lost as a result of extensive resorption. The son was a healthy 43-year-old when a resorption lesion was identified in 1993. A lesion identified on another tooth 12 years later resulted in extraction. CONCLUSIONS: Close relatives of those affected by multiple idiopathic cervical root resorption should be examined carefully for cervical resorption. This study also showed that early treatment can prevent or delay the need for extraction. PMID- 17274729 TI - A view from Riggs: treatment resistance and patient authority - introduction to paper III: "What is psychodynamic psychopharmacology? An approach to pharmacologic treatment resistance", by David Mintz and Barri Belnap. PMID- 17274730 TI - A view from Riggs: treatment resistance and patient authority - III. What is psychodynamic psychopharmacology? An approach to pharmacologic treatment resistance. AB - The authors explore the phenomenon of treatment resistance in relation to medications. They also propose and define a discipline of "psychodynamic psychopharmacology," describe its philosophical underpinnings and make technical recommendations for the psychodynamic treatment of pharmacologic treatment resistance. The authors review the recent literature suggesting a major role for interpersonal and meaning effects in positive pharmacologic treatment outcomes, and suggest that many patients are "treatment-resistant" to medications because an appreciation of the patient's dynamics is not incorporated into an understanding of repeated treatment failures. Common resistances to the effects of medications are considered, as well as ways that patients may become entrenched in treatment resistant illness from counter-therapeutic uses of medications. The authors propose that psychodynamic psychopharmacology advances the overall clinical effectiveness of medications with treatment-resistant patients by integrating a psychodynamic appreciation of the patient with a psychopharmacologic understanding. PMID- 17274731 TI - Neo-psychoanalysis: a paradigm for the 21st century. AB - Freud's metapsychological assumption, splitting mind from brain, created two major and unsolved problems: the relation of the mind with the brain and with outer reality. Recently neuroscientists have focused on the first problem, often basing their work on a category error (mereological fallacy). The second problem may be avoided by considering the coevolution of mind/brain, and by recognizing a non-dualistic symbiosis. Psychodynamic science, built largely on a century of psychoanalytic progress, is proposed as a coequal partner with traditional science in the effort to better understand the theory of knowledge, a central problem of both disciplines. Group selection and downward causation contribute to the recognition of neo-psychoanalysis, a new paradigm to complement the traditional viewpoint. The new view will permit a reunion between traditional and psychodynamic science. Recent fMRI and other data are presented in support of this view. PMID- 17274732 TI - Comparing apples to oranges and making a fruit salad (mixing psychodynamic science and neuroscience): a review of Clay C. Whitehead's "Neo-Psychoanalysis: a paradigm for the 21st century". PMID- 17274733 TI - Finding and refinding the therapeutic alliance: on thinking and thirds. AB - This article represents an attempt to clarify some of our thinking about the component aspects of the analytic relationship as they enter into and play their role in the analytic setting and process. The interaction between transference and alliance generates a dual mental perspective within which the patient experiences and thinks about the analysis and the analyst experiences and thinks about the patient. Concepts of an analytic third, by displacing aspects of the alliance component of this dual relational perspective into either a separate transitional mental space or subjective third, have arisen in the attempt to shed light on the multiplicity of interactional perspectives in analysis: these are discussed and evaluated. The argument concludes that resort to the concept of an analytic third effectively dilutes the direct interpersonal involvement and responsibility of both analyst and patient for transactions within the therapeutic alliance. PMID- 17274734 TI - Neurobiology of dynamic psychotherapy: an integration possible? AB - In the last decades, Kandel's innovative experiments have demonstrated that brain structures and synaptic connections are dynamic. Synapses can be modified by a wide variety of environmental factors, including learning and memory processes. The hypothesis that dynamic psychotherapy process involves memory and learning processes has opened the possibility of a dialogue between neuroscience and psychoanalysis and related psychotherapy techniques. The primary aim of the present article is to critically review the more recent data on neurobiological effects of dynamic psychotherapy in psychiatric disorders. Relevant literature has been selected using the databases currently available online (i.e., PubMed). The literature search has been limited to the past 10 years and to genetic, molecular biology, and neuroimaging studies that have addressed the issue of changes induced by psychotherapy. Most of the genetic studies on mental disorders have demonstrated that psychiatric conditions result from a complex interaction of genetic susceptibility and environmental effects. For none of the many psychiatric conditions investigated has a purely genetic background been found. Molecular biology studies have indicated that gene expression is influenced by several environmental factors, including early experiences, traumas, learning, and memory processes. Neuroimaging studies (using fMRI and PET) have found that not only cognitive but also dynamic psychotherapy has measurable effects on the brain. In addition, psychotherapy may modify brain function and metabolism in specific brain areas. Most of these studies have considered patients with major depressive disorders and compared the effects of psychotherapy with the effect of standard pharmacotherapy. In conclusion, recent results from neuroscience studies have suggested that dynamic psychotherapy has a significant impact on brain function and metabolism in specific brain areas. The possible applications and developments of this new area of research toward the conceptualization of an integrative approach to treatment of psychiatric disorders are discussed. PMID- 17274735 TI - On the limits of psychoanalytic theory: a cautionary perspective. AB - Citing the complexities of the human mind with respect to early development and its functioning in later life, the author cautions against the reliance on any individual psychoanalytic theory in clinical work. Psychoanalytic theories, in general, do not take into account many factors such as the patient's constitutional givens, his or her inborn temperament, family system factors, the impact of the autonomous functions on development, the limits of the child in Piagetian terms, or post-oedipal learning. The analyst's favorite theory may become a belief system that shapes his or her understanding of the patient leading to an imposition of the theory on the data. The analyst's sense of certainty about his or her favorite theory may be based on a transference to the author of the theory or from its fit with his or her own psychological makeup. Cited is Greenson's position (1969/1978) that if he tries to imagine an analytic session with a "true believer" analyst repeating the catechism of his school, he would find it "hard to see this as a living creative experience for either the patient or the therapist" (p. 354). Ultimately, not accountable in terms of any psychoanalytic theory, there is something ineffable, which is the persistent and basically indestructible essence of the person that cannot be explained on the basis of good mothering or on the basis of a facilitating environment. Whether this is thought of as "soul" or "spirit," or even a Winnicottian "true self," it is not something the psychotherapist can omnipotently create. It can only be discovered - unearthed, unburied, cleared away of emotional clutter. PMID- 17274736 TI - Listening to Prozac, with the third ear: a psychoanalytic theory of psychopharmacology. AB - A model of the mind, utilizing constructs from object relations theory, is developed that bridges the conceptual gap between brain functions, influenced by the chemical milieu interior, and the psychodynamic construction of states of mind. A theory of self-regulation and regulation of the self is derived from the archaic mutual psychophysiological regulation between infant and mother that permits the actualization of a metapsychological structure, the internalized "environmental" mother that interpenetrates with chemically alterable brain physiology. This structure forms the background mental matrix of all experience and is maintained/altered either by meaningful (selfobject) relationships or by chemical agents and/or self initiated behavior, which modify the psychophysiological matrix directly via physiology. Linking this construct with a theory of internal object relations derived from Kernberg, and, a body of research documenting state-dependent learning, a clinically applicable theory of the direct (not symbolic) effect of physical events on the construction of experience is realized. PMID- 17274740 TI - Personalized thyroid medicine--the time is now. PMID- 17274741 TI - Human breast cancer tissue expresses high level of type 1 5'-deiodinase. AB - Type 1 5'-deiodinase is one of two isoenzymes that participate in conversion of prohormone thyroxine into triiodothyronine (T3). A decrease in type 1 5' deiodinase expression was observed in renal clear cell carcinoma, thyroid cancer, and lung cancer. The aim of this study was to evaluate type 1 5'-deiodinase activity and mRNA level in breast cancer tissue and non-cancerous surrounding breast tissue. Material was collected from 36 patients undergoing radical mastectomy or local tumor resection. In all non-cancerous breast tissues, type 1 50-deiodinase activity was found to be at a very low or immeasurable level, and type 1 5'-deiodinase mRNA was detected only in 2 out of the 36 samples. By contrast, 20 out of the 36 breast cancer tissues, mainly grades G1 and G2, expressed abundant type 1 5'-deiodinase activity and/or a high mRNA level. Our data demonstrated the presence of type 1 5'-deiodinase in well-differentiated breast cancer tissue. High enzymatic activity of type 1 50-deiodinase can potentially lead to an increase in the production of T3, which may affect target gene transcription, including genes responsible for energy expenditure, growth, differentiation, and proliferation. PMID- 17274739 TI - Nine-year trends and racial and ethnic disparities in women's awareness of heart disease and stroke: an American Heart Association national study. AB - BACKGROUND: The purpose of this study was to evaluate trends in women's awareness, knowledge, and perceptions related to cardiovascular disease (CVD) since 1997, when the American Heart Association initiated a national campaign for women. METHODS AND RESULTS: A nationally representative sample of 1,005 women identified through random digit dialing (mean age 50 years, 71% white) was surveyed in 2006, and results were compared with results of similar surveys conducted in 2003, 2000, and 1997. Awareness, knowledge, and perceptions related to CVD were evaluated using a standardized interviewer-assisted questionnaire. In 2006, awareness of heart disease as the leading cause of death among women was 57%; significantly higher than in prior surveys (p < 0.001). Awareness was lower among black and Hispanic women compared with white women (31% and 29% vs. 68%, p < 0.05), and the racial/ethnic difference has not appreciably changed over time. More than twice as many women felt uninformed about stroke compared to heart disease in 2006 (23% vs. 11%, p < 0.05). Hispanic women were more likely than white women to report that there is nothing they can do to keep themselves from getting CVD (22% vs. 11%, p < 0.05). The majority of respondents (> or = 50%) reported confusion related to basic CVD prevention strategies. CONCLUSIONS: CVD awareness has increased significantly among women since 1997, yet the racial/ethnic gap in awareness has not narrowed. Educational efforts to increase heart disease and stroke awareness should be targeted to racial/ethnic minorities, especially Hispanics. Methods to reinforce basic CVD prevention strategies are needed. PMID- 17274742 TI - Reduction of mammary and liver lipogenesis and alteration of milk composition during lactation in rats by hypothyroidism. AB - OBJECTIVE: The profound impairment in litter growth produced by untreated maternal hypothyroidism (HypoT) may be a consequence of maternal metabolic dysfunctions affecting lactation. In this work we studied the effects of HypoT on mammary and liver lipid metabolism and its consequences on milk quality. DESIGN: We studied the effects of prolonged 6-propyl-2-thiouracil (PTU)-induced HypoT (0.01% PTU in drinking water starting 8 days before mating until sacrifice) on milk macronutrient composition, liver and mammary lipid metabolism and content and serum lipid, and glucose and insulin concentrations in rats on days 7, 15 (L15), and 20 (L20) of lactation. Mammary and hepatic mRNA abundances of lipogenic enzymes were measured using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) on L15 and L20. MAIN OUTCOME: Milk lactose and triglycerides (TG) were reduced by HypoT, as well as mammary acetyl CoA carboxylase (ACC) activity on L15 and L20, and ACC and lipoprotein lipase (LPL) mRNA on L20. HypoT also decreased hepatic ACC activity on both days, ACC mRNA on L15 and liver [(3)H]H(2)O incorporation to TGs and TG content on L20. HypoT diminished insulinemia, increased serum total lipids, and decreased serum TGs on some or all the days of lactation studied. CONCLUSION: HypoT produces a drastic decrease in milk TGs; the main cause for this seems to be the decreases in liver TG synthesis and in circulating TGs, which, along with reduced mammary uptake of fatty acids caused by decreased LPL expression and possibly diminished mammary lipogenesis, result in an impaired mammary output of TGs to the milk. Thus, the impaired growth of the litters of HypoT mothers can be largely attributed to the low milk quality along with the impaired milk ejection. PMID- 17274743 TI - Aqueous iodine equilibria in Mammalian iodination reactions. AB - Regulatory activity has been demonstrated in two classes of iodinated organic species: thyroid hormones (T(3) and T(4)) and iodinated lipids (ILs), e.g. 6-iodo 5-hydroxy-8,11,14-eicosatrienoic acid. The formation of iodinated biomolecules requires iodide oxidation. In mammals iodide oxidation is one of several peroxidase-mediated reactions that serve to reduce hydrogen peroxide. I(2) is one of several reaction products formed by mammalian peroxidases during iodide oxidation. I(2) forms HOI in an aqueous environment which also has the capacity to iodinate organic species. This manuscript examines the potential relationship between the two classes of known mammalian iodinating species. A model describing iodination pathways for organic species in mammals is advanced. The model predicts the formation of ILs under normal dietary intake of iodine. The model was challenged by characterizing the lipids of hogs maintained on a diet containing normal levels of iodine. Iodinated lipids were found to be present in the fatty acids extracted from the thyroid of these hogs. PMID- 17274745 TI - Cytopathology reports from fine needle aspirations of the thyroid gland: can they be improved? AB - Many endocrinologists are dissatisfied with the cytopathology reports from thyroidal aspirates and unsure of how to proceed with the management of their patients. Endocrinologists and cytopathologists should have a symbiotic or complementary professional relationship if patients are going to be well served. The endocrinologist has responsibilities to the pathologist and vice versa. If the endocrinologist performs the thyroidal fine needle aspirations (FNAs), he or she must provide the pathologist with adequate specimens (in terms of quantity or number of cells) that are well smeared so that cells are well preserved and accurate cytologic diagnosis may be rendered. Also, pertinent clinical history and reasonable differential diagnoses should be stated. The pathologist has responsibilities to the endocrinologist. He or she should strive constantly to provide a clear and definite diagnosis. Cytologic reports must be in a "clinical language." By this I mean a language the clinician can understand. The pathologist should not merely provide morphologic descriptions without any clinical meaning. Here I provide my views and suggestions on improving cytopathology reports based on over 30 years' experience of performing and reporting thyroidal FNAs. PMID- 17274744 TI - Apoptosis-induced decrease of intrathyroidal CD4(+)CD25(+) regulatory T cells in autoimmune thyroid diseases. AB - BACKGROUND: We previously showed that the proportion of CD4(+) T cells was lower and both the proportion and intensity of Fas expression on intrathyroidal CD4(+) T cells were higher in the thyroid than in the peripheral blood of patients with autoimmune thyroid disease (AITD). OBJECTIVE: To clarify whether the intrathyroidal CD4(+)CD25(+) regulatory T (Treg) cells are decreased by Fas mediated apoptosis in patients with AITD. DESIGN: We examined intrathyroidal and peripheral lymphocytes in 20 patients with AITD (15 patients with Gravesa disease and five patients with Hashimotoas disease) and peripheral lymphocytes in 10 healthy volunteers by three-color flow cytometry. MAIN OUTCOME: The proportion of CD4(+)CD25(+) cells was lower in the thyroid of patients with AITD than in the peripheral blood of the same patients or the peripheral blood of the healthy subjects. The proportions of CD4(+)CD25(+)CD69() cells and Forkhead box P3 (Foxp3)(+)CD4(+)CD25(+) cells, which constitute more specific Treg subsets than CD4(+)CD25(+) cells, were also lower in the thyroid than in the peripheral blood of patients with AITD. The proportion of apoptotic cells was higher among intrathyroidal CD4(+) cells than among peripheral CD4(+) cells and higher among intrathyroidal CD4(+)CD25(+) cells than among intrathyroidal CD4(+)CD25() cells. CONCLUSION: These results indicate that intrathyroidal Treg cells are decreased in response to apoptosis in patients with AITD. This decrease in Treg cells may contribute to the incomplete regulation of autoreactive T cells in AITD. PMID- 17274746 TI - Goitrous beauty in Artemisia Gentileschi's Judith and her Maidservant. AB - This paper discusses the representation of goiter in Artemisia Gentileschi's painting Judith and her Maidservant. Judith is depicted with a goiter, which despite being the manifestation of a possible hypothyroidism, in no way detracts from her beauty. The case is presented in the wider context of the representation of goiter in art. PMID- 17274747 TI - Thyroidology in the medieval Medical School of Salerno. PMID- 17274748 TI - Factors related to the recurrence of thyroid nodules after surgery for benign radiation-related nodules. AB - OBJECTIVE: Benign thyroid nodules are increased by radiation exposure and recurrences are common. The goal of this study was to determine the factors related to recurrence of nodular disease and the efficacy of thyroid hormone therapy in reducing them. DESIGN, SETTING, AND SUBJECTS: The study population was drawn from a cohort of 4296 people treated before the age of 16 with conventional external radiation for benign conditions of the head and neck between 1939 and the early 1960s. The study group consisted of 632 subjects who had benign nodules removed surgically. At the discretion of their physicians, 426 subjects were treated with thyroid hormone after surgery, 198 were not, and in 8 subjects, thyroid hormone treatment status was unknown. MAIN OUTCOMES: There were 129 (20.4%) subjects who developed new nodules during follow-up. Women had a greater risk of recurrent nodules than men (27.5% vs. 13.5%) and the rate of recurrence correlated inversely with the extent of surgery. The group who took thyroid hormone had a lower recurrence rate than the untreated group (14.2% vs. 34.2%). The risk of recurrence was reduced to 0.69 (0.47-1.01) in thyroid hormone-treated subjects, regardless of extent of surgery, and to 0.66 (0.46-0.97) when only the subjects with less than 75% of their thyroid removed were considered. CONCLUSION: Thyroid hormone therapy reduced recurrences in this irradiated cohort. It should be recommended to all patients with irradiated thyroids and previous thyroid surgery. PMID- 17274749 TI - Renal cell carcinoma metastases to the thyroid gland-8 cases reported. AB - OBJECTIVE: Clinically important, isolated metastases to the thyroid gland is a rare occurrence. Renal cell carcinoma (RCC) is the most common primary tumor site. We report on 8 cases of late onset metachronous thyroid metastases of RCC. DESIGN: Eight patients presented with metachronous thyroid metastases at a median of 12 years (range 9-18 years) after nephrectomy for RCC. Two patients had simultaneous lung and lymph node metastases, respectively. Four patients had been previously operated for other metastases 1 to 5 years earlier, three of them due to pancreatic metastases. The leading symptom was neck enlargement in all but one case. MAIN OUTCOME: Four total thyroidectomies, 3 subtotal resections, and 1 lobectomy were performed. Complete removal of metastases were achieved in all but one case. There was no postoperative morbidity. Six metastases were bilateral, two unilateral. The 4 year overall survival rate following metastasectomy was 53%, median survival from the date of nephrectomy was 21 years. CONCLUSION: Long term survival can be achieved after resection of isolated metachronous RCC metastases to the thyroid gland. Total thyroidectomy is not required, unless it is necessary for complete metastasectomy. PMID- 17274750 TI - Results of a phase I clinical study using dendritic cell vaccinations for thyroid cancer. AB - OBJECTIVE: We assessed the feasibility and efficacy of dendritic cell (DC) therapy for advanced thyroid papillary and follicular cancer. DESIGN: Six Japanese patients (2 men and 4 women; aged 46-72 years, mean 60 years), who were diagnosed as advanced thyroid cancer with refractory distant metastases (papillary, n=5; follicular, n=1), were enrolled. Patients were first vaccinated weekly for 4 weeks with 10(7) autologous tumor lysate-pulsed monocyte-derived mature DCs followed by fortnightly vaccinations for 8 weeks (total=8 vaccinations). Lowdose (350 KIU) interleukin-2 was also administered for 3 days at each vaccination. Clinical response, adverse effects, delayed-type hypersensitivity skin testing (DTH), and IFN-( ) production by peripheral CD3(+) lymphocytes were evaluated. MAIN OUTCOME: Of the 6 patients, disease was assessed as stable in 2 and as progressive in 4. No adverse events were observed. Results of DTH and IFN-( ) production in peripheral lymphocytes did not correlate to the clinical response. CONCLUSIONS: DC immunotherapy could be administered to patients with thyroid papillary or follicular cancer without substantial side effects. PMID- 17274751 TI - Preoperative evaluation of thyroid pathology in patients with primary hyperparathyroidism. AB - In parathyroidectomy, it has been recognized that a shift to a minimally invasive procedure may be accompanied by a possibility of missing thyroid pathology. However, only a few findings concerning preoperative thyroid evaluation have been reported. We investigated the prevalence of concomitant thyroid pathology by preoperative neck ultrasonography (US) in patients with primary hyperparathyroidism. There were 85 patients (66 women, 19 men; mean age 57 years) in the study group. The mean preoperative calcium level was 11.2mg/dL, and the mean intact parathyroid hormone level was 206 pg/mL. All patients underwent neck US following fine-needle aspiration biopsy (FNAB). Of the 85 patients, 21 (24.7%) had thyroid nodules. Among 21 patients with thyroid nodules, 9 (10.6%) had malignant thyroid tumors, while 12 (14.1%) patients had benign thyroid nodules including multinodular goiter. Of the 9 patients with malignant thyroid nodules, 4 had papillary carcinomas with lymph node metastases. The prevalence of thyroid disease associated with hyperparathyroidism is high, and evaluation of the thyroid pathology by US enables the shift from bilateral neck exploration to the minimally invasive parathyroid surgery. PMID- 17274752 TI - Uncovering a rare but critical complication following thyroid surgery: an audit across the UK and Ireland. AB - OBJECTIVE: Serious wound infection after thyroidectomy is uncommon, but actual incidence is not well documented in the literature. In the past a patient in our unit died secondary to fulminant streptococcal sepsis after thyroidectomy for benign disease. This prompted us to audit experience of serious wound infection among British Association of Endocrine Surgery (BAES) members. DESIGN: A questionnaire was posted to BAES members inquiring about experience of major wound infection following cervicotomy, incidence of minor wound infection, and prophylactic and therapeutic antibiotic usage. MAIN OUTCOME: Eight respondents experienced a case of fulminant wound infection after cervicotomy (8% total respondents). Five patients died and, in 6 patients, cases of streptococci were cultured. Then, 9% of respondents used prophylactic antibiotics routinely, 16% sometimes and 75% never. The most commonly used antibiotic was augmentin, and the most common reasons for use among those with a selective policy were re-operative cases (38%) and immunocompromised patients (38%). Also, 40% of respondents experienced major wound infection requiring intravenous antibiotics or surgical drainage. The most common choices of antibiotic used before sensitivities were obtained were augmentin (43%) and flucloxacillin (35%). CONCLUSIONS: Although rare, fulminant streptococcal wound infection after cervicotomy does occasionally occur and carries a high mortality. PMID- 17274754 TI - A rare case of subacute thyroiditis causing thyroid storm. AB - Thyroid storm is a rare but potentially fatal condition that is most frequently associated with Graves' disease. We present the case of a young woman who presented in thyroid storm, later diagnosed as being due to severe subacute thyroiditis. We discuss the diagnostic approach to thyroid storm, the initial management, and eventual treatment and course of subacute thyroiditis. This case illustrates the necessity to include subacute thyroiditis in the differential diagnosis of severe thyrotoxicosis and thyroid storm. PMID- 17274753 TI - Treatment for childhood-onset Graves' disease in Japan: results of a nationwide questionnaire survey of pediatric endocrinologists and thyroidologists. AB - OBJECTIVE AND DESIGN: To determine the present condition of treatment of childhood-onset Graves' disease in Japan, a nationwide questionnaire survey was conducted among councilors of the Japanese Society for Pediatric Endocrinology and the Japan Thyroid Association. MAIN OUTCOME: Responses were received from 125 individuals, and the rate of collection of questionnaires was 47%. Methimazole was selected for first-line initial antithyroid drug therapy by 92% of respondents. Antithyroid drugs tended to be given at larger initial doses and over longer periods of time to childhood-onset patients than to adult patients, and these tendencies were more pronounced for pediatric endocrinologists. Combination therapy with an antithyroid drug and thyroxine was used more frequently by pediatric endocrinologists. Thyroidologists had more experience with radioiodine therapy than pediatric endocrinologists. Opinions regarding preparation of guidelines for the initial dose of methimazole in childhood-onset Graves' disease were almost equally divided among the following: the dose of methimazole should be adjusted according to the severity of disease as in adult cases, methimazole should be started at a dose of 1mg/kg per day in all patients, and the dose should be determined based on results of a randomized study. CONCLUSIONS: The present condition of treatment of childhood-onset Graves' disease in Japan was clarified. PMID- 17274755 TI - Amyloid goiter as a manifestation of primary systemic amyloidosis. AB - Primary amyloidosis involving the thyroid gland is rare and limited to case reports. We report the case of a previously healthy 47-year-old female presenting with a 1-month history of nausea, vomiting, and diffuse thyroid enlargement. Over the next 3 months, she simultaneously developed renal insufficiency dysphagia and hoarseness of voice. Biopsies from the gastric antrum, duodenum, bone marrow, and kidney were positive for vascular deposition of amyloid. Ultrasound of the thyroid revealed diffuse enlargement of the thyroid gland, which was 32.8 ML in volume, with diffuse hyperechogenicity. Fine needle aspiration (FNA) biopsy was positive for amyloid by Congo red staining, and cytology was negative for malignancy. The patient was treated with dexamethasone 40 mg daily on days 1-4, 9 12, and 17-20 for 3 months. On 3-month follow-up, the patient's nausea and vomiting had resolved and renal insufficiency improved. Ultrasound of the thyroid demonstrated decrease in the size of the goiter to 23.2 ML. Amyloid goiter is seen only in approximately 0.04% of patients with primary systemic amyloidosis. No data is currently available regarding treatment of primary amyloidosis and its effect on the goiter. However, we have evidence demonstrating that successful treatment of amyloidosis decreases thyroid enlargement and improves organ dysfunction. PMID- 17274756 TI - False positive uptake in post-treatment iodine-131 whole-body scans secondary to contamination. PMID- 17274758 TI - Non-islet cell tumor hypoglycemia in a patient with poorly differentiated thyroid cancer. PMID- 17274757 TI - Efficacy of selenium treatment in autoimmune thyroiditis demands an intact selenoprotein transport network. PMID- 17274759 TI - Quantitative measurement of anti-TSH receptor antibodies is useful for the evaluation of treatment effect. PMID- 17274760 TI - Substrate specificity and effect on GLUT4 translocation of the Rab GTPase activating protein Tbc1d1. AB - Insulin stimulation of the trafficking of the glucose transporter GLUT4 to the plasma membrane is controlled in part by the phosphorylation of the Rab GAP (GTPase-activating protein) AS160 (also known as Tbc1d4). Considerable evidence indicates that the phosphorylation of this protein by Akt (protein kinase B) leads to suppression of its GAP activity and results in the elevation of the GTP form of a critical Rab. The present study examines a similar Rab GAP, Tbc1d1, about which very little is known. We found that the Rab specificity of the Tbc1d1 GAP domain is identical with that of AS160. Ectopic expression of Tbc1d1 in 3T3 L1 adipocytes blocked insulin-stimulated GLUT4 translocation to the plasma membrane, whereas a point mutant with an inactive GAP domain had no effect. Insulin treatment led to the phosphorylation of Tbc1d1 on an Akt site that is conserved between Tbc1d1 and AS160. These results show that Tbc1d1 regulates GLUT4 translocation through its GAP activity, and is a likely Akt substrate. An allele of Tbc1d1 in which Arg(125) is replaced by tryptophan has very recently been implicated in susceptibility to obesity by genetic analysis. We found that this form of Tbc1d1 also inhibited GLUT4 translocation and that this effect also required a functional GAP domain. PMID- 17274761 TI - Alteration of mitochondrial membrane potential by Spirulina platensis C phycocyanin induces apoptosis in the doxorubicinresistant human hepatocellular carcinoma cell line HepG2. AB - C-PC (C-phycocyanin) is a water-soluble biliprotein from the filamentous cyanobacterium Spirulina platensis with potent antioxidant, anti-inflammatory and anticancerous properties. In the present study, the effect of C-PC was tested on the proliferation of doxorubicin-sensitive (S-HepG2) and -resistant (R-HepG2) HCC (hepatocellular carcinoma) cell lines. These studies indicate a 50% decrease in the proliferation of S- and R-HepG2 cells treated with 40 and 50 microM C-PC for 24 h respectively. C-PC also enhanced the sensitivity of R-HepG2 cells to doxorubicin. R-HepG2 cells treated with C-PC showed typical apoptotic features such as membrane blebbing and DNA fragmentation. Flow-cytometric analysis of R HepG2 cells treated with 10, 25 and 50 microM C-PC for 24 h showed 18.8, 39.72 and 65.64% cells in sub-G(0)/G(1)-phase respectively. Cytochrome c release, decrease in membrane potential, caspase 3 activation and PARP [poly(ADP-ribose) polymerase] cleavage were observed in C-PC-treated R-HepG2 cells. These studies also showed down-regulation of the anti-apoptotic protein Bcl-2 and up-regulation of the pro-apoptotic Bax (Bcl2-associated X-protein) protein in the R-HepG2 cells treated with C-PC. The present study thus demonstrates that C-PC induces apoptosis in R-HepG2 cells and its potential as an anti-HCC agent. PMID- 17274763 TI - Structural study on ligand specificity of human vitamin B12 transporters. AB - Studies comparing the binding of genuine cobalamin (vitamin B12) to that of its natural or synthetic analogues have long established increasing ligand specificity in the order haptocorrin, transcobalamin and intrinsic factor, the high-affinity binding proteins involved in cobalamin transport in mammals. In the present study, ligand specificity was investigated from a structural point of view, for which comparative models of intrinsic factor and haptocorrin are produced based on the crystal structure of the homologous transcobalamin and validated by results of published binding assays. Many interactions between cobalamin and its binding site in the interface of the two domains are conserved among the transporters. A structural comparison suggests that the determinant of specificity regarding cobalamin ligands with modified nucleotide moiety resides in the beta-hairpin motif beta3-turn-beta4 of the smaller C-terminal domain. In haptocorrin, it provides hydrophobic contacts to the benzimidazole moiety through the apolar regions of Arg357, Trp359 and Tyr362. Together, these large side chains may compensate for the missing nucleotide upon cobinamide binding. Intrinsic factor possesses only the tryptophan residue and transcobalamin only the tyrosine residue, consistent with their low affinity for cobinamide. Relative affinity constants for other analogues are rationalized similarly by analysis of steric and electrostatic interactions with the three transporters. The structures also indicate that the C-terminal domain is the first site of cobalamin-binding since part of the beta-hairpin motif is trapped between the nucleotide moiety and the N-terminal domain in the final holo-proteins. PMID- 17274762 TI - A lysine accumulation phenotype of ScIpk2Delta mutant yeast is rescued by Solanum tuberosum inositol phosphate multikinase. AB - Inositol phosphates and the enzymes that interconvert them are key regulators of diverse cellular processes including the transcriptional machinery of arginine synthesis [York (2006) Biochim. Biophys. Acta 1761, 552-559]. Despite considerable interest and debate surrounding the role of Saccharomyces cerevisiae inositol polyphosphate kinase (ScIPK2, ARG82, ARGRIII) and its inositol polyphosphate products in these processes, there is an absence of data describing how the transcripts of the arginine synthetic pathway, and the amino acid content of ScIpk2Delta, are altered under different nutrient regimes. We have cloned an IPMK (inositol phosphate multikinase) from Solanum tuberosum, StIPMK (GenBank(R) accession number EF362785), that despite considerable sequence divergence from ScIPK2, restores the arginine biosynthesis pathway transcripts ARG8, acetylornithine aminotransferase, and ARG3, ornithine carbamoyltransferase of ScIpk2Delta yeast to wild-type profiles. StIPMK also restores the amino acid profiles of mutant yeast to wild-type, and does so with ornithine or arginine as the sole nitrogen sources. Our data reveal a lysine accumulation phenotype in ScIpk2Delta yeast that is restored to a wild-type profile by expression of StIPMK, including restoration of the transcript profiles of lysine biosynthetic genes. The StIPMK protein shows only 18.6% identity with ScIPK2p which probably indicates that the rescue of transcript and diverse amino acid phenotypes is not mediated through a direct interaction of StIPMK with the ArgR-Mcm1 transcription factor complex that is a molecular partner of ScIPK2p. PMID- 17274764 TI - Enhanced structure prediction of gene products containing class III adenylyl cyclase domains. AB - Domain finding algorithms are useful to understand overall domain architecture and to propose biological function to gene products. Automated methods of applying these tools to large-scale genome studies often employ stringent thresholds to recognize sequence domains. The realization of additional domains can be tedious involving manual intervention but can lead to better understanding of overall biological function. We propose a multi-step approach for the further examination of unassigned linker regions that exploits properties such as the conservation of domain architectures of homologous proteins to propose connections. Improved structure prediction is possible starting from initial domain architectures, obtained from simple 'domain finding' techniques, by concentrating on connecting unassigned regions. 254 unassigned regions have been examined in 114 gene products that potentially contain at least one class III adenylyl cyclase domain for a pilot study. Reliable structure prediction was possible for nearly 80% of unassigned regions. New connections were recognized that assign putative structure and function to these regions by indirect searches (26%). Several others (34%) could be associated with three-dimensional models that might pertain to novel folds and new functions with enough structural content and evolutionary conservation. The presence of additional domains will provide further clues to the overall function of the gene products and their recruitment in particular biochemical pathways. PMID- 17274765 TI - Efficient secondary database driven annotation using model organism sequences. AB - The use of sequences from specific organisms for annotation requires that it does not represent great loss of information and that the sequences available suffice for annotation. In order to investigate whether or not sequences from model organisms may suffice for annotation of sequences from the trematode Schistosoma mansoni, we performed local BLAST searches of S. mansoni sequences against other organisms sequences present in the NCBI database nr. Results have been inserted into a relational database and hits to sequences from three model organisms, Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens have been computed and compared to hits to sequences from other organisms present in nr; score values of each alignment have also been registered. Our observations have shown that a large fraction of orthologous proteins exists in the set of sequences from the three model organisms selected, and therefore a similar fraction of transcripts can be annotated when using either nr or model organism datasets. Moreover, hits to model organisms' sequences are largely as informative as nr. Results suggest that model organisms provide a reliable set of sequences to use as a reference database for S. mansoni sequence annotation, showing the clear possibility of using a restricted dataset of expected better quality for functional annotation and therefore supporting secondary database driven annotation approaches. PMID- 17274766 TI - ISHAN: sequence homology analysis package. AB - Sequence based homology studies play an important role in evolutionary tracing and classification of proteins. Various methods are available to analyze biological sequence information. However, with the advent of proteomics era, there is a growing demand for analysis of huge amount of biological sequence information, and it has become necessary to have programs that would provide speedy analysis. ISHAN has been developed as a homology analysis package, built on various sequence analysis tools viz FASTA, ALIGN, CLUSTALW, PHYLIP and CODONW (for DNA sequences). This JAVA application offers the user choice of analysis tools. For testing, ISHAN was applied to perform phylogenetic analysis for sets of Caspase 3 DNA sequences and NF-kappaB p105 amino acid sequences. By integrating several tools it has made analysis much faster and reduced manual intervention. PMID- 17274767 TI - Estimation of membrane proteins in the human proteome. AB - Genomics and proteomics have added valuable information to our knowledgebase of the human biological system including the discovery of therapeutic targets and disease biomarkers. However, molecular profiling studies commonly result in the identification of novel proteins of unknown localization. A class of proteins of special interest is membrane proteins, in particular plasma membrane proteins. Despite their biological and medical significance, the 3-dimensional structures of less than 1% of plasma membrane proteins have been determined. In order to aid in identification of membrane proteins, a number of computational methods have been developed. These tools operate by predicting the presence of transmembrane segments. Here, we utilized five topology prediction methods (TMHMM, SOSUI, waveTM, HMMTOP, and TopPred II) in order to estimate the ratio of integral membrane proteins in the human proteome. These methods employ different algorithms and include a newly-developed method (waveTM) that has yet to be tested on a large proteome database. Since these tools are prone for error mainly as a result of falsely predicting signal peptides as transmembrane segments, we have utilized an additional method, SignalP. Based on our analyses, the ratio of human proteins with transmembrane segments is estimated to fall between 15% and 39% with a consensus of 13%. Agreement among the programs is reduced further when both a positive identification of a membrane protein and the number of transmembrane segments per protein are considered. Such a broad range of prediction depends on the selectivity of the individual method in predicting integral membrane proteins. These methods can play a critical role in determining protein structure and, hence, identifying suitable drug targets in humans. PMID- 17274768 TI - MemO: a consensus approach to the annotation of a protein's membrane organization. AB - Membrane organization describes the relationship of proteins to the membrane, that is, whether the protein crosses the membrane or is integral to the membrane and its orientation with respect to the membrane. Membrane organization is determined primarily by the presence of two features which target proteins to the secretory pathway: the endoplasmic reticulum signal peptide and the ?-helical transmembrane domain. In order to generate membrane organization annotation of high quality, confidence and throughput, the Membrane Organization (MemO) pipeline was developed, incorporating consensus feature prediction modules with integration and annotation rules derived from biological observations. The pipeline classifies proteins into six categories based on the presence or absence of predicted features: Soluble, intracellular proteins; Soluble, secreted proteins; Type I membrane proteins; Type II membrane proteins; Multi-span membrane proteins and Glycosylphosphatidylinositol anchored membrane proteins. The MemO pipeline represents an integrated strategy for the application of state of-the-art bioinformatics tools to the annotation of protein membrane organization, a property which adds biological context to the large quantities of protein sequence information available. PMID- 17274769 TI - Engineering life through Synthetic Biology. AB - Synthetic Biology is a field involving synthesis of novel biological systems which are not generally found in nature. It has brought a new paradigm in science as it has enabled scientists to create life from the scratch, hence helping better understand the principles of biology. The viability of living organisms that use unnatural molecules is also being explored. Unconventional projects such as DNA playing tic-tac-toe, bacterial photographic film, etc. are taking biology to its extremes. The field holds a promise for mass production of cheap drugs and programming bacteria to seek-and-destroy tumors in the body. However, the complexity of biological systems make the field a challenging one. In addition to this, there are other major technical and ethical challenges which need to be addressed before the field realizes its true potential. PMID- 17274771 TI - Protein subcellular localization prediction using a hybrid of similarity search and error-correcting output code techniques that produces interpretable results. AB - In silico prediction of protein subcellular localization based on amino acid sequence can reveal valuable information about the protein's innate roles in the cell. Unfortunately, such prediction is made difficult because of complex protein sorting signals. Some prediction methods are based on searching for similar proteins with known localization, assuming that known homologs exist. However, it may not perform well on proteins with no known homolog. In contrast, machine learning-based approaches attempt to infer a predictive model that describes the protein sorting signals. Alas, in doing so, it does not take advantage of known homologs (if they exist) by doing a simple "table lookup". Here, we capture the best of both worlds by combining both approaches. On a dataset with 12 locations, similarity-based and machine learning independently achieve an accuracy of 83.8% and 72.6%, respectively. Our hybrid approach yields an improved accuracy of 85.9%. We compared our method with three other methods' published results. For two of the methods, we used their published datasets for comparison. For the third we used the 12 location dataset. The Error Correcting Output Code algorithm was used to construct our predictive model. This algorithm gives attention to all the classes regardless of number of instances and led to high accuracy among each of the classes and a high prediction rate overall. We also illustrated how the machine learning classifier we use, built over a meaningful set of features can produce interpretable rules that may provide valuable insights into complex protein sorting mechanisms. PMID- 17274770 TI - SPLITS: a new program for predicting split and intron-containing tRNA genes at the genome level. AB - In the archaea, some tRNA precursors contain intron(s) not only in the anticodon loop region but also in diverse sites of the gene (intron-containing tRNA or cis spliced tRNA). The parasite Nanoarchaeum equitans, a member of the Nanoarchaeota kingdom, creates functional tRNA from separate genes, one encoding the 5'-half and the other the 3'-half (split tRNA or trans-spliced tRNA). Although recent genome projects have revealed a huge amount of nucleotide sequence data in the archaea, a comprehensive methodology for intron-containing and split tRNA searching is yet to be established. We therefore developed SPLITS, which is aimed at searching for any type of tRNA gene and is especially focused on intron containing tRNAs or split tRNAs at the genome level. SPLITS initially predicts the bulge-helix-bulge splicing motif (a well-known, required structure in archaeal pre-tRNA introns) to determine and remove the intronic regions of tRNA genes. The intron-removed DNA sequences are automatically queried to tRNAscan-SE. SPLITS can predict known tRNAs with single introns located at unconventional sites on the genes (100%), tRNAs with double introns (85.7%), and known split tRNAs (100%). Our program will be very useful for identifying novel tRNA genes after completion of genome projects. The SPLITS source code is freely downloadable at http://splits.iab.keio.ac.jp/. PMID- 17274772 TI - Automated molecular library generation of proteic fragments by virtual proteolysis for molecular modelling studies. AB - This paper presents a computer aided design method useful for simulation of a set of proteolytic cleavages upon target proteins obtained from the Brookhaven Data Bank. The method was developed by using algorithms that are able to interface themselves with other software environments, in order to assist computer analyses in the molecular modelling field, and allowing the generation of molecular libraries containing protein fragments produced by simulated proteolysis. These libraries include structures that differ for several amino acid deletions upon specified regions of the primary sequence. Target residues chosen for the simulation are compatible with enzymatic proteolysis methods used in conventional laboratory procedures. Furthermore, algorithms were able to identify a set of chemical-physical properties of the starting proteins, leading the simulation to find out the most suitable residues for proteolysis. The goal of these strategies is to generate fragments that are leaded to maintain the native-like condition of starting molecules, avoiding loss of conformational characteristics of the original tertiary structure. Proteins chosen for generating proteolytic libraries were represented by naphthalene 1,2 dioxygenase and Rigidoporus lignosus laccase. PMID- 17274773 TI - In silico modeling and hydrogen peroxide binding study of rice catalase. AB - Homology modeling of the catalase, CatC cloned and sequenced from rice (Oryza sativa L., cv Ratna an Indica cultivar) has been performed based on the crystal structure of the catalase CatF (PDB code 1m7s) by using the software MODELLER. With the aid of molecular mechanics and molecular dynamics methods, the final model is obtained and is further assessed by PROCHECK and VERIFY - 3D graph, which show that the final refined model is reliable. With this model, a flexible docking study with the hydrogen peroxide, the substrate for catalase, is performed and the results indicate that Arg310, Asp343 and Arg346 in catalase are three important determinant residues in binding as they have strong hydrogen bonding contacts with the substrate. These hydrogen-bonding interactions play an important role for the stability of the complex. Our results may be helpful for further experimental investigations. PMID- 17274774 TI - Theoretical study of Escherichia coli peptide deformylase inhibition by several drugs. AB - Because peptide deformylase (PDF) is essential for the initiation of translation in eubacteria but not in eukaryotes, it is a potentially interesting target for antibiotics. Computer simulation using docking software can be used to model protein-ligand interactions, and in this brief report we describe its use in optimizing the design in PDF-directed inhibitors. PDF was used as target for a set of five inhibitors with substantial structural differences. Docking results show that the compound 1BB2 (actinonin) binds with high affinity to the enzyme and produces the most stable complex, forming nine hydrogen bonds with the enzyme active site. Its binding energy is DeltaG = -31.880 kJ/mol. The modeling study shows that when the methyl group of 1BB2 is replaced with an amine group, the binding energy is increased to -35.316 kJ/mole. This enhancement is more marked (DeltaG = -41.141 kJ/mol) when the propyl group and the five-membered ring of 1BB2 are replaced by an amide group and a phenyl ring, respectively. We describe an attempt to design better antibiotics on the basis of a computer-aided simulation of the interaction between a drug and its target molecule. PMID- 17274776 TI - Patch testing in children--recommendations of the German Contact Dermatitis Research Group (DKG). AB - Allergic contact dermatitis occurs frequently in children. Patch testing is needed to identify the responsible allergens and should be performed in children. We recommend a panel of 12 contact allergens as a standard series in children from 6-12 years. Four additional contact allergens should be tested in case of a positive history or suggestive clinical picture. For patch testing in children, the allergens should be applied for 24 hours and the readings should be performed at 48 and 72 hours. Standardized patch testing makes it possible to systematically investigate allergic contact dermatitis and identify relevant allergens in children. PMID- 17274777 TI - Abuse of anabolic-androgenic steroids and bodybuilding acne: an underestimated health problem. AB - Abuse of anabolic-androgenic steroids (AAS) by members of fitness centers and others in Germany has reached alarming dimensions. The health care system provides the illegal AAS to 48.1 % of abusers. Physicians are involved in illegal prescription of AAS and monitoring of 32.1 % of AAS abusers. Besides health threatening cardiovascular, hepatotoxic and psychiatric long-term side effects of AAS, acne occurs in about 50 % of AAS abusers and is an important clinical indicator of AAS abuse, especially in young men 18-26 years of age. Both acne conglobata and acne fulminans can be induced by AAS abuse. The dermatologist should recognize bodybuilding acne, address the AAS abuse, and warn the patient about other potential hazards. PMID- 17274778 TI - Meta-analysis of published data on incompletely excised basal cell carcinomas of the ear and nose with introduction of an innovative treatment strategy. AB - BACKGROUND: Auricular/nasal basal cell carcinomas (BCC) often require more surgical procedures than BCCs at other sites. METHODS: A meta-analysis of incompletely excised BCCs compares those on the ear and nose to other sites. The combination of photodynamic diagnostics (PDD) and fresh-frozen sections is compared to multi-stage excisions; in each case, the tissue margins were histographically controlled. RESULTS: The relative risk of an incomplete excision of a BCC on the ear/nose is 2.5 fold higher than on the rest of the body. The combination of PDD and micrographic surgery with fresh-frozen sections reduces the length of stay by 42.86 % from median 14 d to 8 d as well as increasing the revenue per patient per day by 41.9 % from 320.61 euro to 454.95 euro with nearly a comparable rate of recurrences after one year. CONCLUSIONS: PDD in combination with single-stage surgery is an equivalent therapy with few side effects and conforming to guidelines. It takes into account both quality assurance and patient preferences. Multicenter, randomized trials seem desirable. PMID- 17274779 TI - Photodynamic treatment of cutaneous leishmaniasis. AB - Leishmaniasis is a widespread arthropod-borne protozoan zoonosis caused by more than 21 Leishmania species. Vectors are sandflies of different genera. The disease is classified into "Old World" versus "New World" leishmaniasis and further subclassified in cutaneous, mucocutaneous and visceral forms. Most therapeutic approaches are not evidence-based. We report a patient with facial cutaneous Leishmania tropica infection which proved to be resistant to various therapeutic regimes. Excellent results were achieved with photodynamic therapy. PMID- 17274780 TI - Successful treatment of generalized eruptive histiocytoma with PUVA. AB - Generalized eruptive histiocytoma (GEH) is a rare benign skin disease mainly affecting adults which belongs to the family of non-Langerhans-cell histiocytoses. A 32-year-old Caucasian woman developed disseminated, monomorphic papules of the trunk after a common cold with sinusitis. Mucous membranes, palms and soles were spared. She also suffered from arthralgia without fever or night sweats. After one month, the patient noticed progression of the reddish papules involving the trunk, extremities and face. Clinical as well as histological examination and immunohistochemistry led to the diagnosis of GEH. The clinical examination and laboratory testing were normal, except for eosinophilia in the peripheral blood and bone marrow. No neoplastic diseases were found during thorough examinations. Systemic PUVA therapy produced rapid regression of the skin lesions. After 10 treatments the lesions began to regress leaving slight papules and multiple brown hyperpigmentations. The lesions resolved completely after 20 PUVA treatments. No relapses occurred. Systemic PUVA therapy represents a promising option for the treatment of GEH. PMID- 17274782 TI - Evidence-based therapy of chronic urticaria. PMID- 17274781 TI - [Certificate: "Occupational Dermatology (ABD)". New curriculum 2006 of the CME seminars of the Task Force of Occupational and Environmental Dermatology]. AB - The certification of experts is an important component in the overall concept of quality management in occupational dermatology. With the certificate "Occupational Dermatology (ABD)" the Task Force on Occupational and Environmental Dermatology (ABD) has developed a comprehensive CME concept in the field of medico-legal evaluations. The ABD seminars meet the current requirements of the statutory accident insurances and social welfare courts. The new CME seminar curriculum 2006 of the ABD takes into account the recent pioneering achievements in occupational dermatology, e.g. the Bamberg leaflet, the optimized dermatologic report and other prevention/early intervention measures. The ABD seminars (total of 21 hrs) are subdivided into 3 consecutive modules: basic, advanced and special seminar (7 hrs each). The seminars are interactive, based on practice-oriented discussions with experts from different disciplines (occupational dermatology, social law). The seminars should be attended in chronological order; there are no time limits during which they must be completed. Prerequisite for the certification is a specialist's degree in dermatology. To maintain the certificate it is expected to attend one of the newly-created ABD "quality management workshops" (7 hrs) within 5-year-intervals; these focus on interdisciplinary case discussions of the current legal regulations and recent social welfare court decisions. More than 400 dermatologists have already been certified by the ABD. PMID- 17274783 TI - [Erythematous plaque with pustules in the upper lip region]. PMID- 17274784 TI - [The temporary lip ligation]. PMID- 17274786 TI - Recommendation: daily sun protection in the prevention of chronic UV-induced skin damage. PMID- 17274785 TI - [The many faces of granuloma annulare]. PMID- 17274787 TI - Adverse drug reactions--no farewell to harms. PMID- 17274788 TI - Patient reporting of suspected adverse drug reactions: a review of published literature and international experience. AB - AIMS: To synthesize data from published studies and international experience to identify evidence of potential benefits and drawbacks of direct patient reporting of suspected adverse drug reactions (ADRs) by patients. METHODS: Structured search of MEDLINE, CINAHL and PsycINFO supplemented by internet searches and requests for information to key contacts. RESULTS: Seven studies (eight papers) were included in the review. None of the studies concerned spontaneous reporting by patients. Information on patient reporting systems was obtained for six countries, with summary data reported by four. Patient reports identified possible new ADRs that had not previously been reported by health professionals. The quality of patient reports appears to be similar to that of health professional reports. There is some evidence that patients report an ADR when they consider their health professional has not paid attention to their concerns. Patient reports may, at least initially, be more time consuming to process. CONCLUSIONS: Overall, the evidence indicates that patient reporting of suspected ADRs has more potential benefits than drawbacks. Evaluation of patient reporting systems is needed to provide further evidence. PMID- 17274789 TI - Repeat adverse drug reactions causing hospitalization in older Australians: a population-based longitudinal study 1980-2003. AB - AIM: To examine trends in the rate of repeat adverse drug reactions (ADRs) causing hospitalization in older Australians and to identify the most common ADRs and drugs most often implicated in repeat and first-time ADRs. METHODS: Analysis of routinely collected hospital record administrative data, with International Classification of Diseases external cause codes for ADRs extracted from the Western Australia (WA) Hospital Morbidity Data System and WA Death Register, for people aged > or =60 years in 1980-2003. RESULTS: A total of 37 296 people aged > or =60 years with an ADR-related hospitalization were identified. Among them, 6853 (18.4%) patients had 10 212 repeat ADRs. Repeat ADRs consistently increased from 1980 and reached 30.3% of all ADRs by 2003. The mean time interval declined with each successive repeat ADR (810, 606 and 299 days for the first, second and higher ranked repeat episodes, respectively). The most common repeat ADRs were nausea/vomiting (8.0%), haemorrhage due to anticoagulants (5.5%), drug-induced osteoporosis (4.8%) and poisoning by cardiovascular agents (3.9%). The drugs most often involved in repeat ADRs were cardiovascular agents (15.6%), antineoplastic drugs (11.0%), corticoids (10.1%), anticoagulants (8.6%), antirheumatics/nonsteroidal anti-inflammatory drugs (5.1%) and opioids (4.9%). The trends of anticoagulants and antineoplastic drugs implicated in repeat ADRs were still rising at the end of the study. The specific drug classes involved in repeat ADRs differed in relative importance from first-time ADRs. CONCLUSIONS: Repeat ADR-related hospitalizations have consistently increased in elderly Australians from 1980 to 2003. Strategies to ensure the safer use of medicines, in particular anticoagulants, in this population are warranted. PMID- 17274790 TI - The impact of hormonal contraceptives on blood pressure, urinary albumin excretion and glomerular filtration rate. AB - AIM: In short-term studies, hormonal contraceptives (HC) have been suggested to induce a rise in blood pressure (BP) and urinary albumin excretion (UAE), while the effect of HC in renal function (GFR) is still under debate. Data on long-term and withdrawal effects of HC use on these outcomes are, however, not available. We therefore studied whether the start and cessation of HC induce changes in BP, UAE and GFR. METHODS: We used data from the PREVEND Study, a prospective cohort of subjects aged 28-75 years. Eligible were women aged < or = 45 years with complete clinical and pharmacy data on baseline and follow-up screening (4 years later). Multivariate regression analysis was used to estimate the effects of HC on BP, UAE and GFR in those who started (n = 73), stopped (n = 117) or continued (n = 183) with those who never used HC (n = 286) as the reference group. RESULTS: BP increased among starters and fell in stoppers. These changes compared with never-users were statistically significant, even after adjustment for relevant variables. UAE increased by 14.2% in starters (P = 0.074) and fell by 10.6% in stoppers (P = 0.021), while GFR fell by 6.3% in starters (P < 0.001) and did not change in stoppers. The effects of stopping HC on UAE and GFR were significantly different compared with changes among never-users, even after adjustment for other variables (P = 0.023 and 0.036, respectively). CONCLUSIONS: The start of HC was independently associated with worsening of BP, UAE and GFR, while stopping HC use resulted in an improvement. These data suggest that long-term HC use (aged 28 45 years) may be deleterious from the cardiovascular and renal point of view, but stopping may result in correction of these effects. PMID- 17274791 TI - Safety of computerized drug management: a case report. PMID- 17274792 TI - A rare cause of finger clubbing in a life-long nonsmoker. PMID- 17274793 TI - Dysgeusia with amlodipine--a case report. PMID- 17274794 TI - Plasma exchange in a patient with primary antiphospholipid syndrome undergoing kidney transplantation. PMID- 17274795 TI - Outcome of allogeneic vascularized knee transplants. AB - Transplantation of vascularized knee joints is a novel approach in Composite Tissue Allotransplantation (CTA). In 1996 our group started a clinical knee transplantation project and six transplantations have been performed since. Key problems identified early were the monitoring of acute rejection and choice of an immunosuppressive regime. One graft was lost due to postoperative infection and one due to of noncompliance where the patient discontinued the immunosuppressant regime. In three cases late rejection lead to necrosis and graft dysfunction after 15, 16 and 24 months, respectively. Exit-strategies were arthrodesis in one patient and Above Knee Amputation in two cases. With retrospective analysis after initial five cases the treatment protocol was improved. The immunosuppressive drug regime was altered, femoral diaphysis and knee joint grafting was combined and a vascularized block of donor skin and subcutaneous tissue was harvested with the graft (sentinel skin graft). The sentinel skin graft enabled us to monitor acute rejection by clinical and histological examination and avoid late rejection by rapid treatment with high dose steroids. In summary, over a four-year period, one of six allogeneic vascularized knee transplants has survived, one was lost from a surgical site infection, one by noncompliance and three by late rejection. Analysis of our data leads us to suggest that knee transplantation should be limited to a combined injury consisting of extensive loss of cartilage and bone, deficient extensor mechanism and soft tissue and skin defects without any signs of infection. Transplantation should only be taken into consideration as last option before Above Knee Amputation in an otherwise healthy patient under 35 years of age. PMID- 17274796 TI - Low-temperature-induced Golgi tubules are transient membranes enriched in molecules regulating intra-Golgi transport. AB - The incubation of HeLa cells at 15 degrees C induces the formation of Golgi tubules, which contain glycosylation enzymes but neither cargo nor matrix proteins. We now show by immunofluorescence and immunoelectron microscopy that these tubules are enriched in a specific set of SNARE and Rab proteins mediating intra-Golgi transport (Gos28, GS15 and Rab6) but excluded others involved in endoplasmic reticulum-Golgi trafficking (Sec22, membrin, Rab 1 and Rab2). In vivo experiments using cyan fluorescent protein-tagged galactosyltransferase showed that most of these tubules are dynamic transient membranes that grow to the cell periphery but then decrease until disappearing into the perinuclear area. Interestingly, in experiments carried out with cells cultured under physiological conditions, Golgi tubules containing Gos28, GS15, Rab6 and glycosylation enzymes and showing in vivo dynamics identical to that detected in low-temperature cultured cells were observed. Together, our results support that low-temperature induced tubules may be representatives of the carriers mediating intra-Golgi recycling of enzymes. PMID- 17274797 TI - Hitch-hiking between cells on lipoprotein particles. AB - Cell surface proteins containing covalently linked lipids associate with specialized membrane domains. Morphogens like Hedgehog and Wnt use their lipid anchors to bind to lipoprotein particles and employ lipoproteins to travel through tissues. Removal of their lipid anchors or decreasing lipoprotein levels give rise to adverse Hedgehog and Wnt signaling. Some parasites can also transfer their glycosylphosphatidylinositol-anchored surface proteins to host lipoprotein particles. These antigen-loaded lipoproteins spread throughout the circulation, and probably hamper an adequate immune response by killing neutrophils. Together, these findings imply a widespread role for lipoproteins in intercellular transfer of lipid-anchored surface proteins, and may have various physiological consequences. Here, we discuss how lipid-modified proteins may be transferred to and from lipoproteins at the cellular level. PMID- 17274798 TI - The phagosome: compartment with a license to kill. AB - Phagosomes are fascinating subcellular structures. After all, there are only a few compartments that are born before our very eyes and whose development we can follow in a light microscope until their contents disintegrate and are completely absorbed. Yet, some phagosomes are taken advantage of by pathogenic microorganisms, which change their fate. Research into phagosome biogenesis has flourished in recent years - the purpose of this review is to give a glimpse of where this research stands, with emphasis on the cell biology of macrophage phagosomes, on new model organisms for the study of phagosome biogenesis and on intracellular pathogens and their interference with normal phagosome function. PMID- 17274799 TI - The interaction of two tethering factors, p115 and COG complex, is required for Golgi integrity. AB - The vesicle-tethering protein p115 functions in endoplasmic reticulum-Golgi trafficking. We explored the function of homologous region 2 (HR2) of the p115 head domain that is highly homologous with the yeast counterpart, Uso1p. By expression of p115 mutants in p115 knockdown (KD) cells, we found that deletion of HR2 caused an irregular assembly of the Golgi, which consisted of a cluster of mini-stacked Golgi fragments, and gathered around microtubule-organizing center in a microtubule-dependent manner. Protein interaction analyses revealed that p115 HR2 interacted with Cog2, a subunit of the conserved oligomeric Golgi (COG) complex that is known another putative cis-Golgi vesicle-tethering factor. The interaction between p115 and Cog2 was found to be essential for Golgi ribbon reformation after the disruption of the ribbon by p115 KD or brefeldin A treatment and recovery by re-expression of p115 or drug wash out, respectively. The interaction occurred only in interphase cells and not in mitotic cells. These results strongly suggested that p115 plays an important role in the biogenesis and maintenance of the Golgi by interacting with the COG complex on the cis-Golgi in vesicular trafficking. PMID- 17274800 TI - Processing and assembly of the dystrophin glycoprotein complex. AB - The assembly, processing and translocation of proteins occur constantly in all cells, and these processes also take place during the genesis, maintenance and repair of skeletal muscle. Skeletal muscle fibers are composed of myofibrils and are surrounded by a muscle plasma membrane, the sarcolemma. The sarcolemma serves as a docking location for many proteins. These proteins are important for establishing the physical connection between the extracellular matrix and the cytoskeleton and play a role in transmitting force related to muscle contraction. This physical connection is maintained through a myriad of proteins including the dystrophin glycoprotein complex (DGC). Normal sarcolemmal function requires proper DGC synthesis and positioning, and perturbation of the DGC leads to muscle membrane instability and disease. PMID- 17274801 TI - Primary laminopathy fibroblasts display altered genome organization and apoptosis. AB - A number of diseases associated with specific tissue degeneration and premature aging have mutations in the nuclear envelope proteins A-type lamins or emerin. Those diseases with A-type lamin mutation are inclusively termed laminopathies. Due to various hypothetical roles of nuclear envelope proteins in genome function we investigated whether alterations to normal genomic behaviour are apparent in cells with mutations in A-type lamins and emerin. Even though the distributions of these proteins in proliferating laminopathy fibroblasts appear normal, there is abnormal nuclear positioning of both chromosome 18 and 13 territories, from the nuclear periphery to the interior. This genomic organization mimics that found in normal nonproliferating quiescent or senescent cells. This finding is supported by distributions of modified pRb in the laminopathy cells. All laminopathy cell lines tested and an X-linked Emery-Dreifuss muscular dystrophy cell line also demonstrate increased incidences of apoptosis. The most extreme cases of apoptosis occur in cells derived from diseases with mutations in the tail region of the LMNA gene, such as Dunningan-type familial partial lipodystrophy and mandibuloacral dysplasia, and this correlates with a significant level of micronucleation in these cells. PMID- 17274803 TI - Y-chromosomal binary haplogroups in the Japanese population and their relationship to 16 Y-STR polymorphisms. AB - We investigated Y chromosomal binary and STR polymorphisms in 263 unrelated male individuals from the Japanese population and further examined the relationships between the two separate types of data. Using 47 biallelic markers we distinguished 20 haplogroups, four of which (D2b1/-022457, O3/-002611*, O3/-LINE1 del, and O3/-021354*) were newly defined in this study. Most haplogroups in the Japanese population are found in one of the three major clades, C, D, or O. Among these, two major lineages, D2b and O2b, account for 66% of Japanese Y chromosomes. Haplotype diversity of binary markers was calculated at 86.3%. The addition of 16 Y-STR markers increased the number of haplotypes to 225, yielding a haplotype diversity of 99.40%. A comparison of binary haplogroups and Y-STR type revealed a close association between certain binary haplogroups and Y-STR allelic or conformational differences, such as those at the DXYS156Y, DYS390m, DYS392, DYS437, DYS438 and DYS388 loci. Based on our data on the relationships between binary and STR polymorphisms, we estimated the binary haplogroups of individuals from STR haplotypes and frequencies of binary haplogroups in other Japanese, Korean and Taiwanese Han populations. The present data will enable researchers to connect data from binary haplogrouping in anthropological studies and Y-STR typing in forensic studies in East Asian populations, especially those in and around Japan. PMID- 17274802 TI - Correlation between genetic variations in Hox clusters and Hirschsprung's disease. AB - Interactions between migrating neural crest cells and the environment of the gut are crucial for the development of the enteric nervous system (ENS). A key signalling mediator is the RET-receptor-tyrosine-kinase which, when defective, causes Hirschprung's disease (HSCR, colon aganglionosis). RET mutations alone cannot account for the variable HSCR phenotype, invoking interactions with as yet unknown, and probably inter-related, loci involved in ENS development. Homeobox (HOX) genes have a major role in gut development as depicted by the enteric Hox code. We investigated whether DNA alterations in HOX genes, either alone or in combination with RET, are implicated in HSCR. Genotyping effort was minimized by applying the HapMap data on Han Chinese from Beijing (CHB). 194 HSCR patients and 168 controls were genotyped using Sequenom technology for 72 tag, single nucleotide polymorphisms (SNPs) distributed along the HOX clusters. The HapMap frequencies were compared to those in our population and standard statistics were used for frequency comparisons. The multifactor-dimensionality-reduction method was used for multilocus analysis, in which RET promoter SNP genotypes were included. Genetic interactions were found between two HOX loci (5'-HOXA13 and 3'UTR-HOXB7) and the RET loci tested. Minor allele frequencies (MAF) of the SNPs tested in our sample were not significantly different from those reported by HapMap when the sample sizes of the populations compared were considered. This is the first evaluation of the HOX genes in HSCR and the first application of HapMap data in a Chinese population. The interacting HOX loci may affect the penetrance of the RET risk allele. HapMap data for the CHB population correlated well with the general Chinese population. PMID- 17274804 TI - Renal and hepatic dysfunction in hypothyroid children. PMID- 17274805 TI - Caesarean delivery and risk of developing asthma in the offspring. AB - AIM: To evaluate the association between caesarean section and risk of developing asthma. METHOD: We evaluated this association in a Danish cohort, comprising of 11,147 mothers and their babies of which 7119 mother-child pairs were included in the analyses. The mothers' reported asthma data on their children were linked to hospitalization records on mode of delivery. RESULTS: The adjusted odds ratio for developing asthma was 1.11 (95% CI, 0.88-1.39) for caesarean sections versus vaginal births. CONCLUSION: We found no evidence that children being delivered by caesarean section have an increased risk of asthma. PMID- 17274807 TI - Enhanced relapse prevention for bipolar disorder--ERP trial. A cluster randomised controlled trial to assess the feasibility of training care coordinators to offer enhanced relapse prevention for bipolar disorder. AB - BACKGROUND: Bipolar Disorder (BD) is a common and severe form of mental illness characterised by repeated relapses of mania or depression. Pharmacotherapy is the main treatment currently offered, but this has only limited effectiveness. A recent Cochrane review has reported that adding psycho-social interventions that train people to recognise and manage the early warning signs of their relapses is effective in increasing time to recurrence, improving social functioning and in reducing hospitalisations. However, the review also highlights the difficulties in offering these interventions within standard mental health services due to the need for highly trained therapists and extensive input of time. There is a need to explore the potential for developing Early Warning Sign (EWS) interventions in ways that will enhance dissemination. METHODS AND DESIGN: This article describes a cluster-randomised trial to assess the feasibility of training care coordinators (CCs) in community mental health teams (CMHTs) to offer Enhanced Relapse Prevention (ERP) to people with Bipolar Disorder. CMHTs in the North West of England are randomised to either receive training in ERP and to offer this to their clients, or to continue to offer treatment as usual (TAU). The main aims of the study are (1) to determine the acceptability of the intervention, training and outcome measures (2) to assess the feasibility of the design as measured by rates of recruitment, retention, attendance and direct feedback from participants (3) to estimate the design effect of clustering for key outcome variables (4) to estimate the effect size of the impact of the intervention on outcome. In this paper we provide a rationale for the study design, briefly outline the ERP intervention, and describe in detail the study protocol. DISCUSSION: This information will be useful to researchers attempting to carry out similar feasibility assessments of clinical effectiveness trials and in particular cluster randomised controlled trials. PMID- 17274806 TI - Mechanical ventilation and lung infection in the genesis of air-space enlargement. AB - INTRODUCTION: Air-space enlargement may result from mechanical ventilation and/or lung infection. The aim of this study was to assess how mechanical ventilation and lung infection influence the genesis of bronchiolar and alveolar distention. METHODS: Four groups of piglets were studied: non-ventilated-non-inoculated (controls, n = 5), non-ventilated-inoculated (n = 6), ventilated-non-inoculated (n = 6), and ventilated-inoculated (n = 8) piglets. The respiratory tract of intubated piglets was inoculated with a highly concentrated solution of Escherichia coli. Mechanical ventilation was maintained during 60 hours with a tidal volume of 15 ml/kg and zero positive end-expiratory pressure. After sacrifice by exsanguination, lungs were fixed for histological and lung morphometry analyses. RESULTS: Lung infection was present in all inoculated piglets and in five of the six ventilated-non-inoculated piglets. Mean alveolar and mean bronchiolar areas, measured using an analyzer computer system connected through a high-resolution color camera to an optical microscope, were significantly increased in non-ventilated-inoculated animals (+16% and +11%, respectively, compared to controls), in ventilated-non-inoculated animals (+49% and +49%, respectively, compared to controls), and in ventilated-inoculated animals (+95% and +118%, respectively, compared to controls). Mean alveolar and mean bronchiolar areas significantly correlated with the extension of lung infection (R = 0.50, p < 0.01 and R = 0.67, p < 0.001, respectively). CONCLUSION: Lung infection induces bronchiolar and alveolar distention. Mechanical ventilation induces secondary lung infection and is associated with further air space enlargement. The combination of primary lung infection and mechanical ventilation markedly increases air-space enlargement, the degree of which depends on the severity and extension of lung infection. PMID- 17274808 TI - Epidemiology of impaction colic in donkeys in the UK. AB - BACKGROUND: Colic (abdominal pain) is a clinical condition of serious concern affecting the welfare and survival of donkeys at the Donkey Sanctuary in the UK. One of the most commonly reported causes is due to impacted ingesta in the large intestine ("impaction colic"). However little is known about the incidence of, or risk factors for, this condition. Here we describe the epidemiology of colic in donkeys, specifically impaction colic. We focus on temporal aspects of the disease and we identify environmental and management related risk factors for impaction colic in UK donkeys. RESULTS: There were 807 colic episodes in the population of 4596 donkeys between January 1st 2000 and March 31st 2005. The majority (54.8%) of episodes were due to a suspected or confirmed diagnosis of impaction of the gastrointestinal tract. The mortality risk for all colics (51.1%) was higher than reported in other equids. The incidence rate of all colics (5.9 episodes per 100 donkeys per year) and of impaction colic (3.2 episodes) was similar to that in horses. A retrospective matched case-control study of all impaction colics from January 2003 (193) indicated that older donkeys, those fed extra rations and those that previously suffered colic were at increased risk of impaction. Lighter body weight, musculo-skeletal problems, farm and dental disease were also significantly associated with a diagnosis of impaction colic. CONCLUSION: To our knowledge this is the first study to estimate the incidence rate of colic in a large population of donkeys in the UK. In contrast to other equids, impaction was the most commonly reported cause of colic. We identified several risk factors for impaction colic. Increasing age, extra rations and previous colic are known risk factors for colic in other equids. Results support the hypothesis that dental disease is associated with impaction colic. Musculo-skeletal problems may be associated with colic for various reasons including change in amount of exercise or time at pasture. Other associated factors (weight and farm) are the subject of further research. Identification of risk factors for impaction colic may highlight high risk donkeys and may allow intervention strategies to be introduced to reduce the incidence of the disease. PMID- 17274809 TI - Parallel evolution of conserved non-coding elements that target a common set of developmental regulatory genes from worms to humans. AB - BACKGROUND: The human genome contains thousands of non-coding sequences that are often more conserved between vertebrate species than protein-coding exons. These highly conserved non-coding elements (CNEs) are associated with genes that coordinate development, and have been proposed to act as transcriptional enhancers. Despite their extreme sequence conservation in vertebrates, sequences homologous to CNEs have not been identified in invertebrates. RESULTS: Here we report that nematode genomes contain an alternative set of CNEs that share sequence characteristics, but not identity, with their vertebrate counterparts. CNEs thus represent a very unusual class of sequences that are extremely conserved within specific animal lineages yet are highly divergent between lineages. Nematode CNEs are also associated with developmental regulatory genes, and include well-characterized enhancers and transcription factor binding sites, supporting the proposed function of CNEs as cis-regulatory elements. Most remarkably, 40 of 156 human CNE-associated genes with invertebrate orthologs are also associated with CNEs in both worms and flies. CONCLUSION: A core set of genes that regulate development is associated with CNEs across three animal groups (worms, flies and vertebrates). We propose that these CNEs reflect the parallel evolution of alternative enhancers for a common set of developmental regulatory genes in different animal groups. This 're-wiring' of gene regulatory networks containing key developmental coordinators was probably a driving force during the evolution of animal body plans. CNEs may, therefore, represent the genomic traces of these 'hard-wired' core gene regulatory networks that specify the development of each alternative animal body plan. PMID- 17274810 TI - Public-private delivery of insecticide-treated nets: a voucher scheme in Volta Region, Ghana. AB - BACKGROUND: Coverage of vulnerable groups with insecticide-treated nets (ITNs) in Ghana, as in the majority of countries of sub-Saharan Africa is currently low. A voucher scheme was introduced in Volta Region as a possible sustainable delivery system for increasing this coverage through scale-up to other regions. Successful scale-up of public health interventions depends upon optimal delivery processes but operational research for delivery processes in large-scale implementation has been inadequate. METHODS: A simple tool was developed to monitor numbers of vouchers given to each health facility, numbers issued to pregnant women by the health staff, and numbers redeemed by the distributors back to the management agent. Three rounds of interviews were undertaken with health facility staff, retailers and pregnant women who had attended antenatal clinic (ANC). RESULTS: During the one year pilot 25,926 vouchers were issued to eligible women from clinics, which equates to 50.7% of the 51,658 ANC registrants during this time period. Of the vouchers issued 66.7% were redeemed by distributors back to the management agent. Initially, non-issuing of vouchers to pregnant women was mainly due to eligibility criteria imposed by the midwives; later in the year it was due to decisions of the pregnant women, and supply constraints. These in turn were heavily influenced by factors external to the programme: current household ownership of nets, competing ITN delivery strategies, and competition for the limited number of ITNs available in the country from major urban areas of other regions. CONCLUSION: Both issuing and redemption of vouchers should be monitored as factors assumed to influence voucher redemption had an influence on issuing, and vice versa. More evidence is needed on how specific contextual factors influence the success of voucher schemes and other models of delivery of ITNs. Such an evidence base will facilitate optimal strategic decision making so that the delivery model with the best probability of success within a given context is implemented. Rigorous monitoring has an important role to play in the successful scaling-up of delivery of effective public health interventions. PMID- 17274813 TI - Managing burn victims of suicide bombing attacks: outcomes, lessons learnt, and changes made from three attacks in Indonesia. AB - INTRODUCTION: Terror attacks in Southeast Asia were almost nonexistent until the 2002 Bali bomb blast, considered the deadliest attack in Indonesian history. Further attacks in 2003 (Jakarta), 2004 (Jakarta), and 2005 (Bali) have turned terrorist attacks into an ever-present reality. METHODS: The authors reviewed medical charts of victims evacuated to the Singapore General Hospital (SGH) Burns Centre during three suicide attacks involving Bali (2002 and 2005) and the Jakarta Marriott hotel (2003). Problems faced, lessons learnt, and costs incurred are discussed. A burns disaster plan drawing on lessons learnt from these attacks is presented. RESULTS: Thirty-one patients were treated at the SGH Burns Centre in three attacks (2002 Bali attack [n = 15], 2003 Jakarta attack [n = 14], and 2005 Bali attack [n = 2]). For the 2002 Bali attack, median age was 29 years (range 20 to 50 years), median percentage of total burn surface area (TBSA) was 29% (range 5% to 55%), and median abbreviated burn severity index (ABSI) was 6 (range 3 to 10). Eight of 15 patients were admitted to the intensive care unit. For the 2003 Jakarta attack, median age was 35 years (range 24 to 56 years), median percentage of TBSA was 10% (range 2% to 46%), and median ABSI was 4 (range 3 to 9). A large number of patients had other injuries. Problems faced included manpower issues, lack of bed space, shortage of blood products, and lack of cadaver skin. CONCLUSION: The changing nature of terror attacks mandates continued vigilance and disaster preparedness. The multidimensional burns patient, complicated by other injuries, is likely to become increasingly common. A burns disaster plan with emphasis on effective command, control, and communication as well as organisation of health care personnel following a 'team concept' will do much to ensure that the sudden onset of a crisis situation at an unexpected time does not overwhelm hospital manpower and resources. PMID- 17274811 TI - Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis. AB - BACKGROUND: Exposure to arsenic concentrations in drinking water in excess of 300 microg/L is associated with diseases of the circulatory and respiratory system, several types of cancer, and diabetes; however, little is known about the health consequences of exposure to low-to-moderate levels of arsenic (10-100 microg/L). METHODS: A standardized mortality ratio (SMR) analysis was conducted in a contiguous six county study area of southeastern Michigan to investigate the relationship between moderate arsenic levels and twenty-three selected disease outcomes. Disease outcomes included several types of cancer, diseases of the circulatory and respiratory system, diabetes mellitus, and kidney and liver diseases. Arsenic data were compiled from 9251 well water samples tested by the Michigan Department of Environmental Quality from 1983 through 2002. Michigan Resident Death Files data were amassed for 1979 through 1997 and sex-specific SMR analyses were conducted with indirect adjustment for age and race; 99% confidence intervals (CI) were reported. RESULTS: The six county study area had a population weighted mean arsenic concentration of 11.00 microg/L and a population-weighted median of 7.58 microg/L. SMR analyses were conducted for the entire six county study area, for only Genesee County (the most populous and urban county), and for the five counties besides Genesee. Concordance of results across analyses is used to interpret the findings. Elevated mortality rates were observed for both males (M) and females (F) for all diseases of the circulatory system (M SMR, 1.11; CI, 1.09-1.13; F SMR, 1.15; CI, 1.13,-1.17), cerebrovascular diseases (M SMR, 1.19; CI, 1.14-1.25; F SMR, 1.19; CI, 1.15-1.23), diabetes mellitus (M SMR, 1.28; CI, 1.18-1.37; F SMR, 1.27; CI, 1.19-1.35), and kidney diseases (M SMR, 1.28; CI, 1.15-1.42; F SMR, 1.38; CI, 1.25-1.52). CONCLUSION: This is some of the first evidence to suggest that exposure to low-to-moderate levels of arsenic in drinking water may be associated with several of the leading causes of mortality, although further epidemiologic studies are required to confirm the results suggested by this ecologic SMR analysis. PMID- 17274812 TI - A comparative study of the actions of alkylpyridinium salts from a marine sponge and related synthetic compounds in rat cultured hippocampal neurones. AB - BACKGROUND: Polymeric alkylpyridinium salts (poly-APS), are chemical defences produced by marine sponges including Reniera sarai. Poly-APS have previously been shown to effectively deliver macromolecules into cells. The efficiency of this closely follows the ability of poly-APS to form transient pores in membranes, providing strong support for a pore-based delivery mechanism. Recently, water soluble compounds have been synthesised that are structurally related to the natural polymers but bear a different number of pyridinium units. These compounds may share a number of bio-activities with poly-APS. Using electrophysiology, calcium imaging and 1,6-diphenyl-1,3,5-hexatriene imaging, the pore forming properties of poly-APS and four related synthetic oligomers have been tested on primary cultured rat hippocampal neurones. RESULTS: Acute application of poly-APS (0.5 microg/ml), reduced membrane potential, input resistance and suppressed action potential firing. Poly-APS evoked inward cation currents with linear current-voltage relationships similar to actions of pore formers on other cell types. Poly-APS (0.005-5 microg/ml) also produced Ca2+ transients in approximately 41% of neurones. The dose-dependence of poly-APS actions were complex, such that at 0.05 microg/ml and 5 microg/ml poly-APS produced varying magnitudes of membrane permeability depending on the order of application. Data from surface plasmon resonance analysis suggested accumulation of poly-APS in membranes and subsequent enhanced poly-APS binding. Even at 10-100 fold higher concentrations, none of the synthetic compounds produced changes in electrophysiological characteristics of the same magnitude as poly-APS. Of the synthetic oligomers tested compounds 1 (monomeric) and tetrameric 4 (5-50 microg/ml) induced small transient currents and 3 (trimeric) and 4 (tetrameric) produced significant Ca2+ transients in hippocampal neurones. CONCLUSION: Poly APS induced pore formation in hippocampal neurones and such pores were transient, with neurones recovering from exposure to these polymers. Synthetic structurally related oligomers were not potent pore formers when compared to poly-APS and affected a smaller percentage of the hippocampal neurone population. Poly-APS may have potential as agents for macromolecular delivery into CNS neurones however; the smaller synthetic oligomers tested in this study show little potential for such use. This comparative analysis indicated that the level of polymerisation giving rise to the supermolecular structure in the natural compounds, is likely to be responsible for the activity here reported. PMID- 17274814 TI - Role of image-guided fine-needle aspiration biopsy in the management of patients with splenic metastasis. AB - BACKGROUND: Splenic metastases are very rare and are mostly diagnosed at the terminal phase of the disease or at the time of autopsy. The cytohistological diagnosis, when done, is made prevalently by splenectomy. Reports on splenic percutaneous biopsies in the diagnosis of splenic metastasis are fragmentary and very poor. The aims of this study are to analyse retrospectively the accuracy, safety and the clinical impact of ultrasound (US)-guided fine-needle aspiration biopsy (UG-FNAB) in patients with suspected splenic metastasis. METHODS: A retrospective analysis of 1800 percutaneous abdominal biopsies performed at our institute during the period from 1993 to 2003 was done and 160 patients that underwent splenic biopsy were found. Among these 160 patients, 12 cases with the final diagnosis of solitary splenic metastases were encountered and they form the basis of this report. The biopsies were performed under US guidance using a 22 gauge Chiba needle. All the patients underwent laboratory tests, CT examination of the abdomen and chest, US examination of abdomen and pelvis. RESULTS: There were 5 women and 7 men, median age 65 years (range 48-80). Eight patients had a known primary cancer at the time of the diagnosis of splenic metastasis: 3 had breast adenocarcinoma, 2 colon adenocarcinoma, 2 melanoma and 1 lung adenocarcinoma. Four patients were undiagnosed at the time of the appearance of splenic metastasis and subsequent investigations showed adenocarcinoma of the lung in 2 patients and colon adenocarcinoma in the remaining 2. There was a complete correspondence between the US and Computed Tomography (CT) in detecting focal lesions of the spleen. The splenic biopsies allowed a cytological diagnosis of splenic metastasis in all the 12 patients and changed clinical management in all cases. Reviewing the 160 patients that underwent UG-FNAB of the spleen we found no complications related to the biopsies. CONCLUSION: These results indicate that UG-FNAB is a successful technique for diagnosis of splenic metastasis allowing an adequate treatment of the affected patients. PMID- 17274815 TI - MDA-7/IL-24 suppresses human ovarian carcinoma growth in vitro and in vivo. AB - BACKGROUND: Previous studies showed that the human melanoma differentiation associated gene-7 (mda-7), also known as interleukin-24 (IL-24), has potent antitumor activity against human and murine cancer cells. However, the majority of these studies were limited to in vitro testing. In the present study, we investigated the antitumor activity of mda-7/IL-24 against human ovarian cancer cells both in vitro and in vivo. RESULTS: In vitro, treatment of ovarian cancer cells with an adenoviral vector carrying the mda-7 gene (Ad-mda7) resulted in inhibition of cell proliferation and induction of cell cycle arrest, leading to apoptosis. We did not observe inhibitory activity in Ad-mda7-treated normal cells. In vivo, treatment of subcutaneous tumor xenografts with Ad-mda7 resulted in significant tumor growth inhibition when compared with that in control groups (p < 0.001). Molecular analysis of ovarian tumor tissue lysates treated with Ad mda7 showed that MDA-7 protein expression was associated with activation of the caspase cascade. CONCLUSION: Our results show that treatment of ovarian cancer cells with mda-7/IL-24 results in growth suppression both in vitro and in vivo. PMID- 17274817 TI - LaPlace's law revisited: cecal perforation as an unusual presentation of pancreatic carcinoma. AB - BACKGROUND: Pancreatic cancer is often locally and distally aggressive, but initial presentation as cecal perforation is uncommon. CASE PRESENTATION: We describe a patient presenting with pneumoperitoneum, found at initial exploration to have a cecal perforation believed to be secondary to a large cecal adenoma, after palpation of the remainder of the colon revealed hard stool but no distal obstruction. Postoperatively, however, the patient progressed to large bowel obstruction and upon reexploration, a mass could now be delineated, encompassing the splenic flexure, splenic hilum, and distal pancreas. Histological evaluation determined this was locally invasive pancreatic adenocarcinoma, and therefore the true etiology of the original cecal perforation. CONCLUSION: Any perforation localized to the cecum must be highly suspicious for a distal obstruction, as dictated by the law of LaPlace. PMID- 17274816 TI - Holoprosencephaly. AB - Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life. PMID- 17274818 TI - Translation and validation of non-English versions of the Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire. AB - BACKGROUND: The Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire is a unidimensional, disease-specific measure developed in the UK and the Netherlands. This study describes its adaptation into other languages. METHODS: The UK English ASQOL was translated into US English; Canadian French and English; French; German; Italian; Spanish; and Swedish (dual-panel methods). Cognitive debriefing interviews were conducted with AS patients. Psychometric/scaling properties were assessed using data from two Phase III studies of adalimumab. Baseline and Week-2 data were used to assess test-retest reliability. Validity was determined by correlation of ASQOL with SF-36 and BASFI and by discriminative ability of ASQOL based on disease severity. Item response theory (Rasch model) was used to test ASQOL's scaling properties. RESULTS: Cognitive debriefing showed the new ASQOL versions to be clear, relevant and comprehensive. Sample sizes varied, but were sufficient for: psychometric/scaling assessment for US English and Canadian English; psychometric but not scaling analyses for German; and preliminary evidence of these properties for the remaining languages. Test-retest reliability and Cronbach's alpha coefficients were high: US English (0.85, 0.85), Canadian English (0.87, 0.86), and German (0.77, 0.79). Correlations of ASQOL with SF-36 and BASFI for US English, Canadian English, and German measures were moderate, but ASQOL discriminated between patients based on perceived disease severities (p < 0.01). Results were comparable for the other languages. US English and Canadian English exhibited fit to the Rasch model (non-significant p-values: 0.54, 0.68), confirming unidimensionality. CONCLUSION: The ASQOL was successfully translated into all eight languages. Psychometric properties were excellent for US English, Canadian English, and German, and extremely promising for the other languages. PMID- 17274820 TI - DarkHorse: a method for genome-wide prediction of horizontal gene transfer. AB - A new approach to rapid, genome-wide identification and ranking of horizontal transfer candidate proteins is presented. The method is quantitative, reproducible, and computationally undemanding. It can be combined with genomic signature and/or phylogenetic tree-building procedures to improve accuracy and efficiency. The method is also useful for retrospective assessments of horizontal transfer prediction reliability, recognizing orthologous sequences that may have been previously overlooked or unavailable. These features are demonstrated in bacterial, archaeal, and eukaryotic examples. PMID- 17274819 TI - Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency markers. AB - BACKGROUND: Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various histological subtypes of this neoplasia. RESULTS: We examined in situ expression of stem cell-related (NANOG, OCT-3/4, KIT, AP-2gamma) and germ cell-specific proteins (MAGE-A4, NY-ESO-1, TSPY) using a tissue microarray consisting of 60 OGCT tissue samples and eight ovarian small cell carcinoma samples. Developmental pattern of expression of NANOG, TSPY, NY-ESO-1 and MAGE-A4 was determined in foetal ovaries (gestational weeks 13-40). The molecular genetic part of our study included search for the presence of Y-chromosome material by fluorescence in situ hybridisation (FISH), and mutational analysis of the KIT oncogene (exon 17, codon 816), which is often mutated in testicular GCTs, in a subset of tumour DNA samples. We detected a high expression of transcription factors related to the embryonic stem cell-like pluripotency and undifferentiated state in OGCTs, but not in small cell carcinomas, supporting the view that the latter do not arise from a germ cell progenitor. Bilateral OGCTs expressed more stem cell markers than unilateral cases. However, KIT was mutated in 5/13 unilateral dysgerminomas, whereas all bilateral dysgerminomas (n = 4) and all other histological types (n = 22) showed a wild type sequence. Furthermore, tissue from five phenotypic female patients harbouring combined dysgerminoma/gonadoblastoma expressed TSPY and contained Y-chromosome material as confirmed by FISH. CONCLUSION: This study provides new data supporting two distinct but overlapping pathways in OGCT development; one involving spontaneous KIT mutation(s) leading to increased survival and proliferation of undifferentiated oogonia, the other related to presence of Y chromosome material and ensuing gonadal dysgenesis in phenotypic females. PMID- 17274821 TI - Boosting with stumps for predicting transcription start sites. AB - Promoter prediction is a difficult but important problem in gene finding, and it is critical for elucidating the regulation of gene expression. We introduce a new promoter prediction program, CoreBoost, which applies a boosting technique with stumps to select important small-scale as well as large-scale features. CoreBoost improves greatly on locating transcription start sites. We also demonstrate that by further utilizing some tissue-specific information, better accuracy can be achieved. PMID- 17274822 TI - Parental influences on adolescent physical activity: a longitudinal study. AB - BACKGROUND: Physical inactivity is increasing among adolescents in the U.S., especially among girls. Despite growing evidence that parents are an important influence on adolescent health, few longitudinal studies have explored the causal relationship between parental influence and physical activity. This study examines how the relationships between parental influences and adolescent physical activity differ by gender and tests whether these relationships are mediated by adolescents' self-esteem and depression. METHODS: Data are from the National Longitudinal Study of Adolescent Health. The sample includes 13,246 youth, grades 7 to 12, interviewed in 1995 and again 1 year later. Logit models were used to evaluate parental influences on achieving five or more bouts of moderate to vigorous physical activity per week [MVPA] and whether the relationship between parental influence and MVPA was mediated by adolescents' level of self-esteem and depression. RESULTS: Family cohesion, parent-child communication and parental engagement positively predicted MVPA for both genders one year later (odds ratios and 95% confidence intervals for females, 1.09 [1.05 1.12], 1.13 [1.07-1.19], 1.25 [1.17-1.33] and males, 1.08 [1.04-1.11], 1.14 [1.07 1.23], 1.23 [1.14-1.33], respectively); however, parental monitoring did not (odds ratio and confidence intervals for females and males, 1.02 [.97-1.07]). For both females and males, self-esteem mediated the relationship between parental influence and physical activity. Depressive symptoms were only a mediator among males. Females reported higher levels of parent-child communication and lower family cohesion compared with males. There were no gender differences in levels of parental monitoring and engagement. Females had significantly lower levels of self-esteem and higher levels of depressive symptoms than males. CONCLUSION: Strategies to promote physical activity among adolescents should focus on increasing levels of family cohesion, parental engagement, parent-child communication and adolescent self-esteem. PMID- 17274823 TI - Methylation: a regulator of HIV-1 replication? AB - Recent characterizations of methyl transferases as regulators of cellular processes have spurred investigations into how methylation events might influence the HIV-1 life cycle. Emerging evidence suggests that protein-methylation can positively and negatively regulate HIV-1 replication. How DNA- and RNA- methylation might impact HIV-1 is also discussed. PMID- 17274826 TI - A little help from my friends: caring for premature babies in a war zone. AB - This paper is a narrative of some aspects of my work as a midwife with Medecins Sans Frontieres (MSF) in West Africa. I was situated in an isolated north-western regional hospital in an area under rebel military control in 2004-2005 in the Cote d'Ivoire during the civil war which divides the north and south of the country. Access to health care is severely curtailed in this politically unstable environment resulting in much avoidable illness including many premature births. It is a short account of methods used to care for premature babies in a resource poor setting. Equipment was basic, necessitating a creative use of available resources. Providing warmth, oxygen and adequate feeding were often sufficient for a successful outcome for many premature babies. This paper is a combination of descriptions of health care interspersed with case studies. PMID- 17274824 TI - Analysis of the replication of HIV-1 forced to use tRNAMet(i) supports a link between primer selection, translation and encapsidation. AB - BACKGROUND: Previous studies have suggested that the process of HIV-1 tRNA primer selection and encapsidation of genomic RNA might be coupled with viral translation. In order to further investigate this relationship, proviruses were constructed in which the primer-binding site (PBS) was altered to be complementary to elongator tRNAMet (tRNAMet(e)) (HXB2-Met(e)) or initiator tRNAMet (tRNAMet(i)) (HXB2-Met(i)). These tRNAMet not only differ with respect to the 3' terminal 18-nucleotides, but also with respect to interaction with host cell proteins during protein synthesis. RESULTS: Consistent with previous studies, HXB2-Met(e) were infectious and maintained this PBS following short-term in vitro culture in SupT1 cells. In contrast, transfection of HBX2-Met(i) produced reduced amounts of virus (as determined by p24) and did not establish a productive infection in SupT1 cells. The low infectivity of the virus with the PBS complementary to tRNAMet(i) was not due to differences in endogenous levels of cellular tRNAMet(i) compared to tRNAMet(e); tRNAMet(i) was also capable of being selected as the primer for reverse transcription as determined by the endogenous reverse transcription reaction. The PBS of HXB2-Met(i) contains an ATG, which could act as an upstream AUG and syphon scanning ribosomes thereby reducing initiation of translation at the authentic AUG of Gag. To investigate this possibility, a provirus with an A to G change was constructed (HXB2 Met(i)AG). Transfection of HXB2-Met(i)AG resulted in increased production of virus, similar to that for the wild type virus. In contrast to HXB2-Met(i), HXB2 Met(i)AG was able to establish a productive infection in SupT1 cells. Analysis of the PBS following replication revealed the virus favored the genome with the repaired PBS (A to G) even though tRNAMet(i) was continuously selected as the primer for reverse transcription. CONCLUSION: The results of these studies suggest that HIV-1 has access to both tRNAMet for selection as the replication primer and supports a co-ordination between primer selection, translation and encapsidation during virus replication. PMID- 17274825 TI - Conservation of the TRAPPII-specific subunits of a Ypt/Rab exchanger complex. AB - BACKGROUND: Ypt/Rab GTPases and their GEF activators regulate intra-cellular trafficking in all eukaryotic cells. In S. cerivisiae, the modular TRAPP complex acts as a GEF for the Golgi gatekeepers: Ypt1 and the functional pair Ypt31/32. While TRAPPI, which acts in early Golgi, is conserved from fungi to animals, not much is known about TRAPPII, which acts in late Golgi and consists of TRAPPI plus three additional subunits. RESULTS: Here, we show a phylogenetic analysis of the three TRAPPII-specific subunits. One copy of each of the two essential subunits, Trs120 and Trs130, is present in almost every fully sequenced eukaryotic genome. Moreover, the primary, as well as the predicted secondary, structure of the Trs120- and Trs130-related sequences are conserved from fungi to animals. The mammalian orthologs of Trs120 and Trs130, NIBP and TMEM1, respectively, are candidates for human disorders. Currently, NIBP is implicated in signaling, and TMEM1 is suggested to have trans-membrane domains (TMDs) and to function as a membrane channel. However, we show here that the yeast Trs130 does not function as a trans-membrane protein, and the human TMEM1 does not contain putative TMDs. The non-essential subunit, Trs65, is conserved only among many fungi and some unicellular eukaryotes. Multiple alignment analysis of each TRAPPII-specific subunit revealed conserved domains that include highly conserved amino acids. CONCLUSION: We suggest that the function of both NIBP and TMEM1 in the regulation of intra-cellular trafficking is conserved from yeast to man. The conserved domains and amino acids discovered here can be used for functional analysis that should help to resolve the differences in the assigned functions of these proteins in fungi and animals. PMID- 17274827 TI - Autoimmune hepatitis-specific antibodies against soluble liver antigen and liver cytosol type 1 in patients with chronic viral hepatitis. AB - BACKGROUND: Non-organ specific autoantibodies are highly prevalent in patients with chronic hepatitis C (HCV). Among them, anti-liver kidney microsomal type 1 (LKM1) antibody--the serological marker of type 2 autoimmune hepatitis (AIH-2)- is detected in up to 11% of the HCV-infected subjects. On the other hand, anti liver cytosol type 1 antibodies (anti-LC1)--either in association with anti-LKM1, or in isolation--and anti-soluble liver antigen antibodies (anti-SLA) have been considered as useful and specific diagnostic markers for AIH. However, their specificity for AIH has been questioned by some recent studies, which have shown the detection of anti-LC1 and anti-SLA by immunoprecipitation assays in HCV patients irrespective of their anti-LKM1 status. The aim of the present study was to test the anti-LC1 and anti-SLA presence by specific enzyme linked immunosorbent assays (ELISAs), in a large group of Greek HCV-infected patients with or without anti-LKM1 reactivity as firstly, immunoprecipitation assays are limited to few specialized laboratories worldwide and cannot be used routinely and secondly, to assess whether application of such tests has any relevance in the context of patients with viral hepatitis since antibody detection based on such ELISAs has not been described in detail in large groups of HCV patients. METHODS: One hundred and thirty eight consecutive HCV patients (120 anti-LKM1 negative and 18 anti-LKM1 positive) were investigated for the presence of anti LC1 and anti-SLA by commercial ELISAs. A similar number (120) of chronic hepatitis B virus (HBV) infected patients seronegative for anti-LKM1 was also tested as pathological controls. RESULTS: Six out of 18 (33%) anti LKM(pos)/HCV(pos) patients tested positive for anti-LC1 compared to 1/120 (0.83%) anti-LKM(neg)/HCV(pos) patients and 0/120 (0%) of the anti-LKM1(neg)/HBV(pos) patients (p < 0.001 for both comparisons). Anti-SLA antibodies were not present in any of the HCV (with or without anti-LKM1) or HBV-infected patients. CONCLUSION: We showed that anti-LC1 and anti-SLA autoantibodies are not detected by conventional assays in a large group of anti-LKM1 negative patients with chronic hepatitis B and C infections. Based on these results we cannot find any justification for the application of anti-LC1 and anti-SLA tests in the routine laboratory testing of viral hepatitis-related autoantibody serology with the only potential exception being the anti-LC1 screening in anti-LKM1(pos)/HCV(pos) patients. PMID- 17274829 TI - Acetyl salicylic acid augments functional recovery following sciatic nerve crush in mice. AB - Cyclin-dependent kinase 5 (CDK-5) appears to play a significant role in peripheral nerve regeneration as CDK-5 inhibition retards nerve regeneration following nerve crush. Anti-inflammatory drug acetyl salicylic acid elevates CDK 5 and reduces ischemia - reperfusion injury in cultured neurons. In this study we have evaluated the effect of acetyl salicylic acid on functional recovery following sciatic nerve crush in mice. Eighteen Swiss albino mice underwent unilateral sciatic nerve crush. Test animals received acetyl salicylic acid (100 mg/kg/day, n = 6 or 50 mg/kg/day, n = 6) and control animals (n = 6) received normal saline for 14 days following surgery. Functional recovery was assessed with improvement in Sciatic Function Index, nociception and gait. In comparison with normal saline treatment, acetyl salicylic acid (100 mg/kg/day) significantly improved functional recovery following sciatic nerve crush. Anti-inflammatory drug acetyl salicylic acid appears to be a promising agent for treating peripheral nerve injuries and hence elucidation of its neuroprotective pathways is necessary. PMID- 17274828 TI - The effect of Cissus quadrangularis (CQR-300) and a Cissus formulation (CORE) on obesity and obesity-induced oxidative stress. AB - AIM: Obesity is generally linked to complications in lipid metabolism and oxidative stress. The aim of this study was to compare the effect of a proprietary extract of Cissus quadrangularis (CQR-300) to that of a proprietary formulation containing CQR-300 (CORE) on weight, blood lipids, and oxidative stress in overweight and obese people. METHODS: The first part of the study investigated the in vitro antioxidant properties of CQR-300 and CORE using 3 different methods, while the second part of the study was a double-blind placebo controlled design, involving initially 168 overweight and obese persons (38.7% males; 61.3% females; ages 19-54), of whom 153 completed the study. All participants received two daily doses of CQR-300, CORE, or placebo and were encouraged to maintain their normal levels of physical activity. Anthropometric measurements and blood sampling were done at the beginning and end of the study period. RESULTS: CQR-300 as well as CORE exhibited antioxidant properties in vitro. They also acted as in vivo antioxidants, bringing about significant (p < 0.001) reductions in plasma TBARS and carbonyls. Both CQR-300 and CORE also brought about significant reductions in weight, body fat, total cholesterol, LDL cholesterol, triglycerides, and fasting blood glucose levels over the respective study periods. These changes were accompanied by a significant increase in HDL cholesterol levels, plasma 5-HT, and creatinine. CONCLUSION: CQR-300 (300 mg daily) and CORE (1028 mg daily) brought about significant reductions in weight and blood glucose levels, while decreasing serum lipids thus improving cardiovascular risk factors. The increase in plasma 5-HT and creatinine for both groups hypothesizes a mechanism of controlling appetite and promoting the increase of lean muscle mass by Cissus quadrangularis, thereby supporting the clinical data for weight loss and improving cardiovascular health. PMID- 17274830 TI - The use of mechanical restraint and seclusion in patients with schizophrenia: a comparison of the practice in Germany and Switzerland. AB - BACKGROUND: The use of coercive measures is an indicator of the quality of psychiatric inpatient treatment. To date, there is no data available to European comparisons on the incidence of such measures. METHODS: The frequency and duration of mechanical restraint and seclusion on patients with a diagnosis of F2 ICD-10 was analysed in seven German and seven Swiss psychiatric hospitals in the year 2004 using three indicators. Differences between German and Swiss hospitals regarding the indicators were tested for statistical significance using Mann Whitney-U-tests. RESULTS: 6.6 % (Switzerland) and 10.4 % (Germany) of admissions respectively were affected by mechanical restraint and 17.8 % (Switzerland) and 7.8 % (Germany) respectively by seclusion. Seclusion as well as mechanical restraint per case were applied significantly more often in German than in Swiss hospitals and were of significantly longer duration in Swiss than in German hospitals. CONCLUSION: The results showed different patterns in the use of seclusion and mechanical restraint across Swiss and German hospitals. For future European research on the use of compulsory measures in routine psychiatric care, there is a need for uniformed definitions, reliable documentation of coercive measures as well as for an identical way of data analysis. To meet these conditions is the first step to achieve European standards for the use of coercive measures. PMID- 17274831 TI - Echocardiography and assessing fluid responsiveness: acoustic quantification again into the picture? AB - Accurate identification of fluid responsiveness has become an important issue in critically ill patients. Pulse pressure and stroke volume variation have been shown to be reliable predictors of fluid responsiveness. Apart from these two valuable techniques, echo-Doppler offers an interesting alternative for estimating the adequacy of filling. Acoustic quantification is a high-tech tool for delineating the blood-tissue interface on-screen in real time. Cannesson and coworkers utilized this technique in ventilated patients to assess stroke area changes, with the intention being to predict fluid responsiveness. PMID- 17274832 TI - Acute renal failure in critically ill HIV-infected patients. AB - Acute renal failure (ARF) is common among hospitalized HIV-infected patients. To our knowledge, however, data regarding ARF in HIV-infected patients in the intensive care unit are still lacking. PMID- 17274833 TI - Obesity hormone leptin: a new target in breast cancer? AB - Leptin is a multifunctional hormone produced mainly by the adipose tissue and involved in the regulation of food intake and energy balance. In addition, leptin can stimulate mitogenic and angiogenic processes in peripheral organs. Because leptin levels are elevated in obese individuals and excess body weight has been shown to increase breast cancer risk in postmenopausal women, attempts have been made to evaluate whether leptin can promote breast cancer. Data obtained in cell and animal models and analyses of human breast cancer biopsies indeed suggest such an involvement. Furthermore, a recent report clearly shows that targeting leptin signaling may reduce mammary carcinogenesis. Thus, leptin should become a new attractive target in breast cancer. PMID- 17274836 TI - Jumping the shark. AB - In popular-culture, 'jumping the shark' refers to an abandoning of core values in an attempt to appeal to dwindling audiences, a metaphor that might be reasonably be applied to some areas of genomics-based research. PMID- 17274834 TI - HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks. AB - EGFR-type receptor tyrosine kinases achieve a broad spectrum of cellular responses by utilizing a set of structurally conserved building blocks. Based on available crystal structures and biochemical information, significant new insights have emerged into modes of receptor control, its deregulation in cancer, and the nuances that differentiate the four human receptors. This review gives an overview of current models of the control of receptor activity with a special emphasis on HER2 and HER3. PMID- 17274837 TI - The intelligence in developing systems for molecular biology. AB - A report on the 14th Annual International Conference on Intelligent Systems for Molecular Biology (ISMB), Fortaleza, Brazil, 6-10 August 2006. PMID- 17274838 TI - Due caution using early beta-blockers for acute myocardial infarction. PMID- 17274839 TI - Genome re-annotation: a wiki solution? AB - The annotation of most genomes becomes outdated over time, owing in part to our ever-improving knowledge of genomes and in part to improvements in bioinformatics software. Unfortunately, annotation is rarely if ever updated and resources to support routine reannotation are scarce. Wiki software, which would allow many scientists to edit each genome's annotation, offers one possible solution. PMID- 17274840 TI - Signaling netwErks get the global treatment. AB - Two landmark studies of cell signaling, by RNA interference and phosphoproteomics, provide complementary global views of the pathways downstream of receptor kinases, including those regulated by Erks. PMID- 17274841 TI - Analysis of genetic systems using experimental evolution and whole-genome sequencing. AB - The application of whole-genome sequencing to the study of microbial evolution promises to reveal the complex functional networks of mutations that underlie adaptation. A recent study of parallel evolution in populations of Escherichia coli shows how adaptation involves both functional changes to specific proteins as well as global changes in regulation. PMID- 17274842 TI - Parasite vaccines - recent progress and problems associated with their development. AB - The treatment and prevention of parasitism in both humans and livestock continues to rely almost exclusively on the use of antiparasitic drugs - an approach which has limitations, particularly as reinfection, which occurs rapidly in endemic regions, is not prevented. In addition, the widespread appearance of drug resistant parasites of animals (Kaplan, 2004;) together with emerging evidence of resistance problems in human parasites (Fallon et al. 1995; Ismail et al. 1996; De Clerq et al. 1997; East African Network for Monitoring Antimalarial Treatment, 2003), emphasise the importance of developing alternative methods of control, with anti-parasite vaccines a prime target. PMID- 17274843 TI - High road, low road? Choices and challenges on the pathway to a malaria vaccine. AB - Malaria causes much physical and economic hardship in endemic countries with billions of people at risk. A vaccine would clearly benefit these countries, reducing the requirement for hospital care and the economic impact of infection. Successful immunization with irradiated sporozoites and the fact that repeated exposure to malaria induces partial immunity to infection and high levels of protection against the clinical manifestations, suggest that a vaccine is feasible. Numerous candidate antigens have been identified but the vaccine, which has been promised to be 'just round the corner' for many years, remains elusive. The factors contributing to this frustratingly slow progress are discussed including gaps in the knowledge of host/parasite biology, methods to induce potent cell-mediated immune responses, the difficulties associated with defining immune correlates of protection and antigen production and delivery. Finally, the use of attenuated organism vaccines is discussed. PMID- 17274844 TI - Vaccination as a control strategy against the coccidial parasites Eimeria, Toxoplasma and Neospora. AB - The protozoan parasites Eimeria spp. Toxoplasma gondii and Neospora caninum are significant causes of disease in livestock worldwide and T. gondii is also an important human pathogen. Drugs have been used with varying success to help control aspects of these diseases and commercial vaccines are available for all three groups of parasites. However, there are issues with increasing development of resistance to many of the anti-coccidial drugs used to help control avian eimeriosis and public concerns about the use of drugs in food animals. In addition there are no drugs available that can act against the tissue cyst stage of either T. gondii or N. caninum and thus cure animals or people of infection. All three groups of parasites multiply within the cells of their host species and therefore cell mediated immune mechanisms are thought to be an important component of host protective immunity. Successful vaccination strategies for both Eimeria and Toxoplasma have relied on using a live vaccination approach using attenuated parasites which allows correct processing and presentation of antigen to the host immune system to stimulate appropriate cell mediated immune responses. However, live vaccines can have problems with safety, short shelf-life and large-scale production; therefore there is continued interest in devising new vaccines using defined recombinant antigens. The major challenges in devising novel vaccines are to select relevant antigens and then present them to the immune system in an appropriate manner to enable the induction of protective immune responses. With all three groups of parasites, vaccine preparations comprising antigens from the different life cycle stages may also be advantageous. In the case of Eimeria parasites there are also problems with strain-specific immunity therefore a cocktail of antigens from different parasite strains may be required. Improving our knowledge of the different parasite transmission routes, host-parasite relationships, disease pathogenesis and determining the various roles of the host immune response being at times host protective, parasite protective and in causing immunopathology will help to tailor a vaccination strategy against a particular disease target. This paper discusses current vaccination strategies to help combat infections with Eimeria, Toxoplasma and Neospora and recent research looking towards developing new vaccine targets and approaches. PMID- 17274845 TI - Current status of vaccine development against Theileria parasites. AB - The tick-borne protozoan parasites Theileria parva and Theileria annulata cause economically important diseases of cattle in tropical and sub-tropical regions. Because of shortcomings in disease control measures based on therapy and tick control, there is a demand for effective vaccines against these diseases. Vaccines using live parasites have been available for over two decades, but despite their undoubted efficacy they have not been used on a large scale. Lack of infrastructure for vaccine production and distribution, as well as concerns about the introduction of vaccine parasite strains into local tick populations have curtailed the use of these vaccines. More recently, research has focused on the development of subunit vaccines. Studies of immune responses to different stages of the parasites have yielded immunological probes that have been used to identify candidate vaccine antigens. Immunisation of cattle with antigens expressed in the sporozoite, schizont or merozoite stages has resulted in varying degrees of protection against challenge. Although the levels of protection achieved have not been sufficient to allow exploitation for vaccination, there are clearly further lines of investigation, relating to both the choice of antigens and the antigen delivery systems employed, that need to be pursued to fully explore the potential of the candidate vaccines. Improved knowledge of the molecular biology and immunology of the parasites gained during the course of these studies has also opened up opportunities to refine and improve the quality of live vaccines. PMID- 17274846 TI - Regulations and procedures in parasite vaccine development. AB - Although immunisation protocols for a wide variety of parasitic diseases have been developed, it is often questioned why these do not always reach the market. In this review information about the regulations and procedures that apply to licensing the production and marketing of medicinal preparations, especially parasite vaccines, is presented. These general regulations specify issues on product (quality, safety, efficacy and potency) and production (facilities and consistency). Vaccine developers and manufacturers have to comply with these regulations, which may involve years of research and development. Moreover, where the manufacturer claims specific features of the product, these claims have to be corroborated by (experimental) data. A series of principles has been used to develop vaccines against parasite infections varying from the use of (attenuated) live vaccines to killed vaccines and subunit vaccines. The implications of some specific regulatory issues associated with these approaches are discussed. PMID- 17274848 TI - Vaccines against the zoonotic trematodes Schistosoma japonicum, Fasciola hepatica and Fasciola gigantica. AB - Schistosoma japonicum, Fasciola hepatica and F. gigantica are digenetic trematodes and, therefore, possess similar life cycles. While schistosomiasis japonica has for a long time been recognised as a major disease of both humans and animals, infection with fasciolids has only been considered of relevance to animals. However, a number of recent reports indicate that fasciolosis is becoming a serious public health problem, especially in South America, Egypt and Iran (sporadic cases are also on the increase throughout Europe). Vaccines targeted at animals could play an important role in controlling these three diseases in animals and, by blocking transmission of infection, have a concurrent beneficial effect on disease in humans. Approaches towards identifying and producing vaccines against these parasites are similar and are discussed in this review. PMID- 17274847 TI - Cestode vaccines: origins, current status and future prospects. AB - Recombinant vaccines have been developed which are highly effective in preventing infection with Taenia ovis in sheep, Taenia saginata in cattle, Taenia solium in pigs and Echinococcus granulosus in livestock animals. T. ovis and T. saginata are economically significant parasites and the commercial success or otherwise of vaccines against them will rely on their economic value. E. granulosus and T. solium are zoonotic parasites that cause cystic hydatid disease and neurocysticercosis, respectively, in humans. Vaccines against these parasites have been developed to assist with the control of transmission of the human diseases rather than for prevention of infections in livestock per se. Regions of high prevalence for cystic hydatid disease and neurocysticercosis occur primarily in the developing world. As a consequence, vaccines against them are of little or no commercially interest - they are Orphan Vaccines. Lack of commercial interest in these vaccines has made public sector support for their development necessary well beyond the research phase trough into completion of commercial scale-up and other more commercially-related assessments. Practical use of the vaccines will require commercial-scale production according to international manufacturing standards. Identifying partners and support in this endeavour is now of prime importance in efforts to achieve the potential of these vaccines as new tools for the control of cystic hydatid disease and neurocysticercosis. PMID- 17274849 TI - Vaccines against blood-feeding nematodes of humans and livestock. AB - This paper summarises the progress towards vaccine development against the major blood-feeding nematodes of man and livestock, the hookworms and Haemonchus contortus, respectively. The impact of the diseases and the drivers for vaccine development are summarized as well as the anticipated impact of the host immune response on vaccine design. The performance requirements are discussed and progress towards these objectives using defined larval and adult antigens, many of these being shared between species. Specific examples include the Ancylostoma secreted proteins and homologues in Haemonchus as well as proteases used for digestion of the blood meal. This discussion shows that many of the major vaccine candidates are shared between these blood-feeding species, not only those from the blood-feeding stages but also those expressed by infective L3s in the early stages of infection. Challenges for the future include: exploiting the expanding genome information for antigen discovery, use of different recombinant protein expression systems, formulation with new adjuvants, and novel methods of field testing vaccine efficacy. PMID- 17274851 TI - Leishmania vaccines: progress and problems. AB - Leishmania are protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world resulting in an estimated 12 million new cases each year. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. Leishmaniasis is considered one of a few parasitic diseases likely to be controllable by vaccination. The relatively uncomplicated leishmanial life cycle and the fact that recovery from infection renders the host resistant to subsequent infection indicate that a successful vaccine is feasible. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunisation with protein or DNA vaccines. However, to date no such vaccine is available despite substantial efforts by many laboratories. Advances in our understanding of Leishmania pathogenesis and generation of host protective immunity, together with the completed Leishmania genome sequence open new avenues for vaccine research. The major remaining challenges are the translation of data from animal models to human disease and the transition from the laboratory to the field. This review focuses on advances in anti-leishmania vaccine development over the recent years and examines current problems hampering vaccine development and implementation. PMID- 17274850 TI - Vaccines for amoebiasis: barriers and opportunities. AB - Amoebiasis, infection by the protozoan parasite Entamoeba histolytica, remains a global health problem, despite the availability of effective treatment. While improved sanitation could lead to the eradication of this disease, it is unlikely that this will occur worldwide in the foreseeable future; thus alternative measures must be pursued. One approach is to develop a vaccine to prevent this deadly disease. Clinical studies indicate that mucosal immunity may provide some protection against recurrent intestinal infection with E. histolytica, but there is no clear evidence that protective immunity develops after amoebic liver abscess. Over the past decade, progress in vaccine development has been facilitated by new animal models that allow better testing of potential vaccine candidates and the application of recombinant technology to vaccine design. Oral vaccines and DNA-based vaccines have been successfully tested in animals models for immunogenicity and efficacy. There has been significant progress on a number of fronts, but there are unanswered questions regarding the effectiveness of immune responses in preventing disease in man and, as yet, no testing of any of these vaccines in humans has been performed. In addition, there are strong economic barriers to developing an amoebiasis vaccine and questions about how and where an effective vaccine would be utilized. PMID- 17274852 TI - Vaccination against ectoparasites. AB - Ectoparasites of livestock are of great economic and social importance but their effective control remains difficult. The feasibility of vaccination as a novel control measure was established over a decade ago with the commercial release of a recombinant vaccine against the cattle tick Boophilus microplus. Since then, research has continued on ticks and other ectoparasites. While some ectoparasite species will undoubtedly be refractory to immunological control, for others there has been a steady accumulation of knowledge of partially protective antigens, now accelerating through the application of genomic technologies. Nevertheless, progress towards usable, commercially available vaccines has been limited by a number of factors. The number of highly effective antigens is still very small. Although some classes of antigen have been investigated in more detail than others, we have no systematic knowledge of what distinguishes an effective antigen. Much hope has been placed on the potential of multi-antigen mixtures to deliver the efficacy required of a successful vaccine but with little experimental evidence. The application of current knowledge across parasite and host species needs to be explored but little has been done. In most cases, the path to commercial delivery is uncertain. Although many constraints and challenges remain, the need for vaccines and our capacity to develop them can only increase. PMID- 17274853 TI - Electrophysiological evidence of the motivational salience of drug cues in opiate addiction. AB - BACKGROUND: Drug-related stimuli reliably induce craving in experimental paradigms, yet are rarely cited by drug users as major precipitants of relapse. We examined the motivational significance of drug cues in opiate dependence, by exploring their impact on central attentional processes. METHOD: Fourteen methadone-maintained subjects and 14 matched controls were studied. Subjects performed a novel active visual oddball task, consisting of opiate-related and matched neutral pictures, some of which (the oddballs) included a white cup. Subjects were fitted with a 32-channel electrode cap. The P300 for each stimulus category was identified using temporal principal components analysis. RESULTS: The P300 elicited by opiate stimuli was significantly larger than that elicited by neutral stimuli in the methadone-maintained group but not in the controls. There was also a non-significant trend for the opiate stimuli to elicit larger P300s than the oddball stimuli in the addicted group. CONCLUSIONS: These results suggest that drug cues acquire motivational salience and automatically capture attentional resources in opiate addicts, even when engaged in a non-drug-related task. Enhanced P300s to drug cues may provide an important biological marker of crucial psychological mechanisms relevant to addiction. PMID- 17274855 TI - Can the 12-item General Health Questionnaire be used to measure positive mental health? AB - BACKGROUND: Well-being is an important determinant of health and social outcomes. Measures of positive mental health states are needed for population-based research. The 12-item General Health Questionnaire (GHQ-12) has been widely used in many settings and languages, and includes positively and negatively worded items. Our aim was to test the hypothesis that the GHQ-12 assesses both positive and negative mental health and that these domains are independent of one another. METHOD: Exploratory (EFA) and confirmatory (CFA) factor analyses were conducted using data from the British Household Panel Survey (BHPS) and the Health Survey for England (HSE). Regression models were used to assess whether associations with individual and household characteristics varied across positive and negative mental health dimensions. We also explored higher-level variance in these measures, between electoral wards. RESULTS: We found a consistent, replicable factor structure in both datasets. EFA results indicated a two-factor solution, and CFA demonstrated that this was superior to a one-factor model. These factors correspond to 'symptoms of mental disorder' and 'positive mental health'. Further analyses demonstrated independence of these factors in associations with age, gender, employment status, poor housing and household composition. Statistically significant ward-level variance was found for symptoms of mental disorder but not positive mental health. CONCLUSIONS: The GHQ-12 measures both positive and negative aspects of mental health, and although correlated, these dimensions have some independence. The GHQ-12 could be used to measure positive mental health in population-based research. PMID- 17274854 TI - An epidemiological investigation of affective disorders with a population-based cohort of 1023 adults with intellectual disabilities. AB - BACKGROUND: Intellectual disabilities (ID) are common and lifelong. People with ID have health inequalities compared with the general population, but little is known about the epidemiology of affective disorders in this population. This study was undertaken to determine the point prevalence of affective disorders, and to investigate factors associated with depression. METHOD: This population based study (n=1023) included comprehensive individual assessments with each person. A two-stage process was used for diagnosis of affective disorders. Factors independently associated with depression were investigated through logistic regression analysis. RESULTS: The point prevalence was higher than that reported previously for the general population; DC-LD yielded 3.8% for depression and 0.6% for mania. Additionally, 1.0% had bipolar disorder currently in remission, and 0.1% first episode of mania currently in remission. Similar to general population findings, depression was associated with female gender, smoking, number of preceding family physician appointments, and preceding life events. Important differences were the association of not having a hearing impairment, and the trends for not living in deprived areas, and being married. Unlike general population findings, not having daytime occupation and obesity were not independently associated; nor was previous long-stay hospital residence, severity of ID, or sensory impairments. CONCLUSIONS: This study has found a high point prevalence of affective disorders in adults with ID. The factors associated with depression have differences to general population findings. An understanding of this is important in order to develop appropriate interventions, public strategy and policy, to reduce existing health inequalities. PMID- 17274856 TI - Incidence of bacterial meningitis in Asia using enhanced CSF testing: polymerase chain reaction, latex agglutination and culture. AB - To enhance the detection of bacterial meningitis in an East Asian surveillance study, we employed cerebrospinal fluid (CSF) bacterial culture, latex agglutination (LA) and polymerase chain reaction-enzyme immunoassay (PCR-EIA) testing for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). The sensitivity and specificity of CSF PCR-EIA testing was compared to LA and culture. A meningitis case was defined by one positive result for any of the three tests. The sensitivity of H. influenzae CSF PCR-EIA, LA, and culture was 100%, 40% and 57.5% respectively; and for Sp CSF PCR-EIA, LA and culture, the sensitivity was 100%, 58.3% and 66.7%, respectively. Hib and Sp specificity was 100% by each method. CSF PCR-EIA was more sensitive than culture or LA for the detection of Hib and Sp meningitis cases increasing their incidence by 74% and 50% compared to culture respectively. CSF PCR-EIA should be included for the detection of bacterial meningitis in surveillance studies. PMID- 17274857 TI - Vaginal symptoms and bacterial vaginosis (BV): how useful is self-report? Development of a screening tool for predicting BV status. AB - Vaginal complaints compel an evaluation of bacterial vaginosis (BV), however, many cases of BV are asymptomatic. We evaluated the sensitivity and specificity of vaginal symptoms in the diagnosis of BV and examined the utility of creating a BV screening tool using clinical, behavioural and demographic characteristics. A total of 1916 pregnant women were included in this analysis. In total, 757 women screened positive for BV and over one third of BV-positive women presented without any lower genital tract symptoms (39.4%). African American race, abnormal vaginal odour, and smoking were independently related to BV positivity. A BV screening tool including these three factors was fairly predictive of BV status with the area under the ROC curve equal to 0.669. This three-item prediction rule may be useful in identifying high- risk pregnant women in need of BV screening and, given the high specificity, accurately identify the group of BV-negative pregnant women. PMID- 17274858 TI - Outbreak of Salmonella Braenderup infections associated with Roma tomatoes, northeastern United States, 2004: a useful method for subtyping exposures in field investigations. AB - Salmonella Braenderup is an uncommon serotype in the United States. In July 2004, a multistate outbreak of Salmonella Braenderup diarrhoeal infections occurred, with 125 clinical isolates identified. To investigate, we conducted a case control study, enrolling 32 cases and 63 matched controls. Cheese, lettuce and tomato eaten at restaurants all appeared to be associated with illness. To further define specific exposures, we conducted a second study and asked managers of restaurants patronized by patients and controls about cheese, lettuce and tomato varieties used in dishes their patrons reported consuming. This information was obtained for 27 cases and 29 controls. Roma tomatoes were the only exposure significantly associated with illness (odds ratio 4.3, 95% confidence interval 1.2-15.9). Roma tomatoes from two restaurants were traced back to a single tomato packing house. The methods used in this field investigation to define specific exposures may be useful for other foodborne outbreaks. PMID- 17274859 TI - Experimental transmission of a ranavirus disease of common toads (Bufo bufo) to common frogs (Rana temporaria). AB - During investigations of epidemic frog mortality in Britain, a novel fatal systemic haemorrhagic disease of common toads was discovered. This disease resembles a systemic haemorrhagic disease of common frogs in Britain, which is one of a range of fatal disease syndromes, characterized by systemic haemorrhages, skin ulceration or a combination of these lesions, caused by ranavirus infection. Ranavirus previously isolated from diseased toads was inoculated into common frogs to evaluate if this virus could infect and cause disease in common frogs. All virus-inoculated frogs died with systemic haemorrhages between 6 and 8 days post-inoculation, giving similar results to those produced by the inoculation of frogs with ranavirus cultured from naturally diseased frogs. These results indicate that the same, or similar, viruses are affecting both frogs and toads in the field and confirm that ranavirus has emerged as an important cause of amphibian mortality in Britain. PMID- 17274860 TI - Multiple sites of exposure in an outbreak of ornithosis in workers at a poultry abattoir and farm. AB - Cases of ornithosis amongst workers on a rural duck abattoir and farm were notified from late 2003 to health authorities in Victoria, Australia. In May 2004 we conducted a serological survey to identify the extent of exposure to Chlamydophila psittaci amongst workers and a case control study to identify high risk work areas for ornithosis-related pneumonia. Some workers in all occupational groups showed serological evidence of exposure, while those with pneumonia were more likely to have worked in the slaughtering area of the abattoir (adjusted odds ratio 16.7, 95% confidence interval 1.3-207). High exposure to blood and feathers from recently killed birds is likely to represent an occupational hazard to workers, but pneumonia did occur in workers without these exposures. We recommended respiratory protection for all abattoir workers and improvements to airflow and reduction of environmental contamination in high risk work areas to prevent further cases. PMID- 17274863 TI - [Importance of recognizing macrophage activation syndrome]. PMID- 17274862 TI - Cocaine versus tetracaine in septoplasty: a prospective, randomized, controlled trial. AB - BACKGROUND: Successful local anaesthesia is of critical importance for the success of septoplasty, and many surgeons prefer to use cocaine for this purpose. The aim of this study was to evaluate the efficacy of cocaine 4 per cent solution, compared with tetracaine 2 per cent plus adrenaline, as a local anaesthetic for patients undergoing septoplasty. METHODS: From December 2002 to February 2005, a prospective, randomized, controlled trial was conducted. One hundred and eight patients underwent septoplasty under local anaesthesia. Patients were randomly classified into group A and group B, in which was used respectively cocaine 4 per cent solution and tetracaine 2 per cent solution plus adrenaline. A visual analogue scale was used to evaluate the severity of patients' pain during their procedure. RESULTS: Group B (tetracaine; mean rank=43.77) reported significantly less pain (p<0.001) compared with group A (cocaine; mean rank=65.23). CONCLUSIONS: On the basis of these findings, we recommend tetracaine as the first choice anaesthetic for nasal septoplasty; the use of cocaine should be limited. PMID- 17274861 TI - The bacteriology of pneumonia diagnosed in Western Australian emergency departments. AB - We used Western Australian emergency department data linked to hospital morbidity, death and microbiology data to describe the bacteriology of pneumonia according to age. The 'atypical' organisms and viruses were not assessed. A total of 6908 patients over a 3-year period were given an emergency department diagnosis of pneumonia, 76.9% were admitted and 6.3% died in hospital. Blood was cultured from 52.9% of patients with 6.4% growing potential pathogens. Streptococcus pneumoniae was the most common organism isolated and accounted for 92% of pathogens in those aged <15 years. Isolation of Enterobacteriaceae species tended to increase with age and accounted for around 25% of isolates from the elderly. Sputum was cultured from 25.3% of patients and bacteria were isolated from 30.3% of samples, commonly Haemophilus influenzae and S. pneumoniae. Isolates from sputum showed no distinct trend across age groups. These patterns question the value of routine blood and sputum cultures and have implications for empiric therapy for the elderly. PMID- 17274864 TI - [Macrophage activation syndrome: genetic basis and therapeutic hypothesis]. PMID- 17274865 TI - [Macrophage activation syndrome in Chinese children with systemic onset juvenile idiopathic arthritis]. AB - OBJECTIVE: To review and analyze the clinical features, treatment, and outcome of macrophage activation syndrome (MAS) in children with systemic onset juvennil rheumatoid arthritis (SOJRA). METHOD: Retrospective review and analysis were performed on cases with MAS from a prospectively collected database of children with SOJRA from the year of 2003 to 2006 in the Hospital. RESULTS: Twenty four patients (21 boys, 3 girls) were diagnosed as having MAS with SOJRA. Mean age of the patients with MAS at diagnosis was 7 years, and the duration prior to diagnosis of MAS was 12 months. No trigger factors were found except in one case whose MAS was triggered by use of methotrexate and in another by parvovirus B19 infection. High grade fever, new onset hepatosplenomegaly and lymphadenopathy, pancytopenia, liver dysfunction were common clinical features in all the 24 cases (100%). Bleeding from skin, mucous membrane and gastrointestinal tract were noted in 9 cases (38%). Twelve (50%) cases had CNS dysfunction (high intracranial pressure, seizure and coma). Six cases (25%) developed ARDS. One patient suffered from renal damage. The laboratory test revealed elevated live enzymes and ferritin, decreased value of ESR, albumin, complete blood count and fibrinogen in all the 24 cases. Bone marrow examination supported the diagnosis of definite hemophagocytosis in the 24 cases. Lymph node biopsy was done for one case and histopathological examination showed that the node was full of activated macrophage. As to treatment, five cases only received high dose steroids (three of them died), 14 cases were treated with high dose steroids plus cyclosporine (one died), two were treated with steroids plus cyclosporine and etoposide (none died). The causes of deaths were ARDS and CNS involvement. In three of the cases who died, treatment was given up by their parents. CONCLUSIONS: MAS is a rare and potentially fatal complication of SOJRA. Most of our patients were male. Bone marrow studies support the diagnosis. CNS involvement and ARDS were poor prognostic signs. Early diagnosis and aggressive therapy are essential. PMID- 17274866 TI - [Macrophage activation syndrome in children with systemic onset juvenile idiopathic arthritis: analysis of 13 patients]. AB - OBJECTIVE: Macrophage activation syndrome (MAS) is a rare but life-threatening complication in children with rheumatic diseases, particularly systemic-onset juvenile idiopathic arthritis (SOJIA). Because of the potential fatality of this condition, prompt recognition and immediate therapeutic intervention are important. This study reviewed the data of MAS in 13 cases with SOJIA. METHODS: Retrospective review was performed on the precipitating events, clinical manifestations, laboratory data, treatment, and outcome of macrophage activation syndrome in 13 children with SOJIA seen from 1996 to 2005. RESULTS: Over the past 10 years the unit has had 90 new patients with SOJIA. Thirteen of those patients (14.4%) developed MAS during the course of their primary SOJIA, of whom ten were male. All patients were noted to have active SOJIA prior to developing MAS; 3 patients had medications, which were considered as trigger factors; 8 had infections prior to MAS, in two of them the infections were possible triggers. All the patients had high grade fever; 12 cases (92.3%) had hepatomegaly; 10 patients (76.9%) had coagulopathy, and eight patients (61.5%) had central nervous system dysfunction. The counts of platelet, white blood cells and the mean erythrocyte sedimentation rate fell dramatically in all patients; hyperferritinemia was identified in 8 patients, in 5 of whom serum ferritin (SF) was >or= 10,000 microg/L; in 8 (72.7%) of 11 cases fibrinogen was or= 2.5 mmol/L in 9 (69.2%) of 13 cases. CONCLUSION: MAS is a rare and potentially fatal complication of children with SOJIA. Primary disease activity, medications and infections preceding MAS were all important triggers. The strongest clinical discriminators were hepatomegaly, hemorrhages and central nervous system dysfunction. The strongest laboratory tests were decreased counts of platelet and white blood cells, decreased ESR and fibrinogen, dramatically increased SF and TG. It calls for the immediate treatments, particularly with cyclosporin A, which are often effective. PMID- 17274868 TI - [A severe complication of rheumatic disorders - macrophage activation syndrome]. PMID- 17274867 TI - [Macrophage activation syndrome in children with rheumatic disorders: a retrospective study on 6 patients]. AB - OBJECTIVE: To study the clinical manifestations of rheumatic disorders with macrophage activation syndrome (MAS) in children. METHODS: The authors characterized MAS by carrying out a retrospective study on patients who were identified during the past 12 years in Tianjin Children's Hospital. RESULTS: Six cases (4 females, 2 males) were studied. Four had typical systemic onset juvenile idiopathic arthritis (SOJIA), two had systemic lupus erythematosus (SLE) with lupus nephritis. Clinical manifestations at diagnosis, which occurred in the lower activity state of these primary diseases, included high spiking fever (in 5 cases) or high fever (in 1), hepatosplenomegaly (in 6), lymphadenopathy (in 6), profound decrease of all 3 blood cell lines (in 6), significant injury of liver (in 6), diseminated intravascular coagulation (DIC)-like picture (in 2), and central nervous system dysfunction (in 3). Hypofibrinogenemia, elevated liver enzymes and hypertriglyceridemia were found consistently. The phagocytic histiocytes with plasmacytosis were found in 3 bone marrow smears (not done in others). MAS was presumed to have been precipitated by viral infections in 3 patients, two had evidences for herpes simplex virus infection and one for hepatitis A virus infection. The treatment regimen was tailored to each patient, as the clinical course was variable. CONCLUSIONS: MAS may not only be most frequently seen in children with SOJIA, but also in those with other rheumatic diseases, and may be a syndrome that is more common than previously thought. Infection may be main trigger factor for MAS. The immunoapheresis combined with immunochemotherapy may be optimal for severe injury of the liver in patients with MAS. PMID- 17274869 TI - [Hypoglycemic brain injury in premature infants]. PMID- 17274870 TI - [Summary of the symposium on macrophage activation syndrome]. PMID- 17274872 TI - [Diagnostic value of lung biopsy in children with diffuse interstitial lung disease]. PMID- 17274873 TI - [Reply to the questions concerning macrophage activation syndrome]. PMID- 17274874 TI - [Considerations in clinical diagnosis of childhood macrophage activation syndrome]. PMID- 17274871 TI - [Macrophage activation syndrome in 2 cases with Kawasaki disease: clinical analysis and review of literature]. PMID- 17274875 TI - [Immunosuppressive therapy for 54 children patients with acquired severe aplastic anemia]. AB - OBJECTIVE: Aplastic anemia is characterized by bone marrow failure and marked reduction of white blood cells, red blood cells and platelets in peripheral blood. Clinical studies have shown that immunosuppressive therapy greatly prolonged the long-term survival of some patients with aplastic anemia. But in severe aplastic anemia (SAA) patients whose ANC was < 0.5 x 10(9)/L, platelets were < 20 x 10(9)/L, very low bone marrow proliferation and high death rate were observed. The present study aimed to evaluate the efficacy of immunosuppressive treatments with cyclosporine A (CSA) alone or CSA combined with antithymocyte globin (ATG) in children with acquired SAA. METHODS: Fifty-four cases with SAA were treated with immunosuppressive agents mentioned above in our department from Jan. 1997 to June 2003, 31 of the cases had treated with CSA combined with ATG. There were 18 cases with SAA type I and 13 cases with SAA type II in CSA combined with ATG group, and 13 cases had very severe aplastic anemia. The other 23 cases were treated with CSA alone (CSA group), 10 of these cases had SAA-I and 13 had SAA-II, and 5 cases had very severe aplastic anemia. The responsive rate, relapse, adverse reactions and event free survival (EFS) were compared between CSA combined with ATG group and CSA group. RESULTS: The proportions of patients with different types of the disease and severity were comparable between the two groups. The responsive time of the CSA combined with ATG group and CSA group was 2.5 months and 3.5 months, respectively (P < 0.05), the responsive rate in two groups was 81% (25/31) and 52% (12/23), respectively (chi(2) = 4.962, P < 0.05). In 37 cases who were responsive to therapy, the relapse rate was 8% (2/25) and 50% (6/12) respectively (chi(C)(2) = 6.143, P < 0.05). There were no significant differences in adverse reactions to the immunosuppressive agents. All cases were followed-up for more than 1 year, and the event-free survival over one year in these two groups was 81% (25/31) and 52% (12/23), respectively. Forty-seven cases were followed-up for more than two years, and the event-free survival was 74% (20/27) and 50% (10/20), respectively (P < 0.01). Twelve cases were followed-up for over 5 years. There were no secondary tumor, myelodysplastic syndrome and other colony diseases. CONCLUSION: The immunosuppressive therapies for acquired severe aplastic anemia in childhood were effective. The effect of CSA combined with ATG was better than that of CSA alone, and the relapse rate was lower with the combined treatment. However, the long-term effect needs longer follow-up studies to evaluate. PMID- 17274876 TI - [Relationship between neonatal polycythemia and brain damage]. AB - OBJECTIVE: To investigate the clinical manifestations, imaging characteristics as well as prognosis of neonatal polycythemia complicated with brain damage. METHODS: One hundred and sixteen in-patients with neonatal polycythemia admitted to our hospital during January 2003 to October 2005 were analyzed. Their clinical manifestations were observed. Craniocerebral ultrasonic examination (2D, 3D), CT and MRI were employed to dynamically observe the craniocerebral imaging variances as well as the cerebral hemodynamic variations and near infrared spectroscopy (NIR) was adopted to test the cerebral oxygenation. Twenty-two cases with moderate or severe disease were followed up for 3 to 12 months. RESULTS: Out of the 116 polycythemic neonates, 53 cases had brain damages, of whom 31 had mild, 14 had moderate, and 8 had severe damages. Cranial imaging alterations were mostly ischemic injuries of various areas of different severity. The severity of brain damage was closely related to the duration of polycythemia, oxygen saturation of cerebral tissues as well as cerebral hemodynamic abnormalities. Brain injury was likely to occur in those whose polycythemia persisted for more than three days. The regional saturation of oxygen (rSO(2)) in mild brain injury cases was found to be 52.1%, while it was 47.1% in moderate and severe brain injury cases. Compared to the 58% as found in non-brain injury cases, the variance was found to be statistically significant (F = 104.466, P < 0.01). Among the cases with brain injury, cerebral hemodynamics displayed a slowdown in the blood flow velocity in the cerebral anterior artery and medium artery during the systolic phase and/or the diastolic phase. The abnormality ratio was closely related to the severity of brain injury. Through the chi(2) test the variance was proved to be statistically highly significant (chi(2) = 18.889, P < 0.01), however it was not correlated with the increase of the initial levels of hemoglobin (Hb) and hematocrit (HCT) (P > 0.05). During the follow up, neurological developmental abnormalities of various severity were found to exist in the cases with moderate (5/12) and severe disease (7/8), while cerebral palsy or epilepsy was not yet found. CONCLUSION: Neonatal polycythemia might tend to bring about a reduction in the perfusion of cerebral blood flow and damaged cerebral oxygenation metabolism which in turn might lead to cerebral ischemic injury, which in some of the moderate and severe cases might lead to long-term neurological complications. Imaging investigations especially craniocerebral ultrasonic examination could be the practical means for the early diagnosis and evaluation of prognosis. PMID- 17274877 TI - [Detection of group B streptococcus in the cases died of neonatal pneumonia]. AB - OBJECTIVE: From the 1970s, group B streptococci (GBS) have been widely recognized as an important pathogen in neonatal infectious disease, and it emerged as the leading cause of neonatal morbidity and mortality in the Western world. However, there are few data on the prevalence of neonatal GBS infections in China. The aim of this retrospective study was to estimate whether GBS is an important pathogen in severe neonatal pneumonia, and to develop a method for detection of GBS infections in fatal neonatal pneumonia. METHODS: A total of 234 neonatal cases (0 - 28 days) died in Beijing Children's Hospital from 1953 to 2004 were enrolled in this study. They were divided into two groups. Two hundred cases diagnosed as neonatal pneumonia were assigned to study group and the remaining 34 cases died of neonatal hemolysis or surgical operation without any confirmed infectious diseases were designated as control group. Formalin-fixed, paraffin-embedded lung tissues were used as source for total genomic DNA extraction. PCR and Southern blot analyses were applied to detect GBS specific cfb gene target sequence. And the clinical data of these cases were reviewed as well. RESULTS: In the study group, 52 cases were detected positive for GBS DNA by PCR (26%), 130 cases were positive by Southern blot (65%). In the control group, 1 case was detected positive GBS DNA by PCR (3%), and 6 cases were positive by Southern blot (18%). The positive rate was significantly lower in the control group than that in the study group (PCR, chi(2) = 8.82, P < 0.01; Southern blot, chi(2) = 26.77, P < 0.01). The positive rate in the neonates younger than 7 days (early-onset) was significantly higher than that in neonates older than 7 days (late-onset) (PCR: 37% vs. 13%, chi(2) = 15.537, P < 0.01; Southern blot: 72% vs. 52%, chi(2) = 4.37, P < 0.05). In the positive early-onset cases, 39% of whom were born prematurely (29/74). Out of the 200 cases, 75 had complete clinical data. Neither blood nor lung culture for GBS was performed in any of these cases. But risk factors were identified for 35 cases, such as premature delivery, low birth weight, premature rupture of the membrane and abnormal amniotic fluid. GBS was positive in all these cases. Severe apnea appeared to be a common symptom and was present in most of the early-onset GBS-positive cases, while cough and wheezing were found in most of the late-onset GBS-positive cases. In the control group, one PCR positive case was suffered from malignant teratoma. The other 5 positive cases confirmed by Southern blot were diagnosed as kernicterus, hepatoma, aproctia complicating with cysti-urethral fistula, neonatal physio logical bleeding and aproctia complicated with archo-perineal fistula. CONCLUSION: Group B Streptococcus is an important pathogen in fatal neonatal pneumonia, especially in early-onset cases. southern blot may be a sensitive method to detect GBS infection in archival tissues. In the clinical work, more attention should be paid to the neonates with GBS risk factors. And GBS detection and prevention in neonates should be put into clinical practice. PMID- 17274878 TI - [Peripheral blood mononuclear cell of neonates infected with hepatitis B virus]. AB - OBJECTIVE: To study the mechanism and significance of peripheral blood mononuclear cell (PBMC) of neonates infected with hepatitis B virus (HBV). METHODS: Eighty-four HBsAg-positive and HBeAg-negative mothers and their newborns were recruited in this study. Sixteen hepatitis B virus markers (HBVM)-negative mothers and their neonates were served as control. All these cases had no symptoms of hepatitis, serious pregnancy complications and preexisting disease. Age, gestational age and the method of delivery were matched in two groups (P > 0.05). Five ml blood samples were taken from the peripheral vein of the pregnant women before delivery and from neonates within 24 hours after birth, before inoculation of HBV vaccine (HBVac). Serum and PBMC were isolated from 2 ml and 3 ml samples respectively. The sera, PBMC and the last supernatant of PBMC washing were stored at -80 degrees C. HBVM of neonates were detected by using enzyme linked immunosorbent assay (ELISA). HBV DNA in serum, PBMC and the last supernatant of PBMC washing of mothers and neonates were detected by using a nested-polymerase chain reaction (n-PCR). Two pairs of oligonucleotide primers, the outer primer pair for first PCR and inner primer pair for second PCR, designed according to region S of HBV genome were synthesized at Shanghai Cell Biology Institute of Chinese Academy of Sciences. The neonates who were HBV DNA positive in PBMC but HBsAg and HBV DNA negative in serum were followed up for one year, HBsAb in serum and HBV DNA in PBMC were observed in the neonates. RESULTS: (1) The positive rate of HBV DNA in 84 serum and PBMC of mothers were 53.57% and 40.48%, respectively (chi(2) = 2.891, P > 0.05). All the results were weakly positive. (2) Twenty-four (28.57%) newborns in the study group were infected, including 7 who were only HBV DNA positive in serum, 11 only HBV DNA positive in PBMC and 6 in both, all the results were weakly positive. HBsAg was negative in all the newborns. None of the neonates in control group was infected with HBV. There was significant difference between the two groups (chi(2) = 4.55, P < 0.05). (3) Of all the study cases, 11 (13.10%) neonates were HBV DNA weakly positive in PBMC but HBsAg and HBV DNA negative in serum. Of their mothers, 5 were only HBV DNA positive in serum, 2 only positive in PBMC and 4 positive in both serum and PBMC. Seven of the 11 neonates were followed up for one year and at the end of follow-up, 4 were HBsAb positive and HBV DNA negative in PBMC; 3 were HBsAb negative, and among the 3 cases HBV DNA in 2 was still positive in PBMC, HBsAg and HBV DNA in serum were negative in all the 7 neonates. CONCLUSION: (1) HBV DNA positivity either in serum or in PBMC in mothers can result in infection of PBMC with HBV in their neonates. (2) PBMC infection with HBV can exist for a long time in neonates while HBsAg and HBV DNA are negative in serum, and may result in vaccination failure in neonates. PMID- 17274879 TI - [Mutation of growth hormone receptor gene in patients with short stature]. AB - OBJECTIVES: The mutations of growth hormone receptor (GHR) gene results in growth hormone insensitivity (Laron syndrome) or partial growth hormone insensitivity. This study aimed to understand the relation between mutations of GHR gene and short stature with non-growth-hormone deficiency, and the clinical feature of the patients with the GHR gene mutations. METHODS: (1) Forty-seven patients with non growth-hormone deficiency and short stature were enrolled in this study, 33 were male and 14 female. The age of the patients were at a range of 2 - 16 years. (2) The mutations of GHR gene were identified by PCR-SSCP and DNA sequencing. (3) The characteristics of the GHR mutation was assumed by screening for the same mutations in patients' family members and the control samples. RESULTS: (1) Four GHR mutations were identified in 5 patients with non-growth-hormone deficiency: H56R, G148E, IVS6-30, -31CA > TG and IVS8 + 10G > C. These mutations were located within the extracellular domain of GHR and not reported before. Five patients were the heterozygous of H56R, G148E, IVS6-30, -31CA > TG and IVS8 + 10G > C. The detection rate of mutant heterozygous individual accounted for 10.6% (5/47). The mutations were considered non-polymorphism by the GHR gene analysis in patients' family members and control samples. (2) Comparison of the amino acid sequence of different species and the position of the mutations H56R and G148E in the GHR protein structure suggested impact of the mutations on the protein function. (3) A polymorphism site was identified in exon 6 of GHR gene: G168G (GGA > GGG). The allelic frequency of G168G had no difference between the patients with non-growth hormone deficiency and control samples but had significant difference between Chinese and Caucasian. It seems that the G168G was a polymorphism and has no relationship with the height stature. However, there was the allele diversity in different races. CONCLUSION: The mutations of GHR gene were detected in the patients with non-growth-hormone deficiency. Special attention should be paid clinically to its potential pathogenesis for short stature. PMID- 17274881 TI - [Gene mutation analysis in four Chinese patients with multiple carboxylase deficiency]. AB - OBJECTIVE: Multiple carboxylase deficiency (MCD) is an autosomal recessive disorder. MCD is characterized by skin rash, metabolic acidosis, vomiting and psychomotor retardation. Depending on deficiency of the enzyme, MCD includes two different forms, biotinidase deficiency (BTD, OMIM 253260) and holocarboxylase synthetase deficiency (HLCSD, OMIM 253270). In this study, we analyzed gene mutations of four Chinese MCD patients and to explore the mutation spectrum and possibility of a molecular diagnosis. METHODS: All exons and their flanking introns of biotinidase gene and HLCS gene were screened by polymerase chain reaction combined with DNA direct sequencing in four Chinese MCD patients. Genomic DNA was extracted using a kit from the peripheral blood leukocytes of each patient. PCR amplification products were checked by 2% agarose gel electrophoresis and were subsequently sequenced with both the forward and reverse primers. RESULTS: All patients showed mutations in HLCS gene, whereas no mutation was found in biotinidase gene, proving that all the four patients had HLCS deficiency. Four previously reported mutations in HLCS gene were detected (Y456C, R508W, D634N and 780delG). A missense mutation of 1522C > T in exon 11 of HLCS gene, which was a homozygotic mutation, was identified in patient 1; a mutation of 1522C > T in exon 11 combined with a mutation of 1367A > G in exon 9, which was a compound heterozygotic mutation, was identified in patient 2; a mutation of 1522C > T in exon 11 combined with a mutation of 1900G > A in exon 13, which was a compound heterozygotic mutation, was identified in patient 3; a mutation of 1522C > T in exon 11 combined with a mutation of 780delG in exon 7, which was a compound heterozygotic mutation, was identified in patient 4. All the parents were carriers of mutations. No additional carrier of this four mutations was identified from 50 samples of Chinese controls. CONCLUSION: The 1522C > T (R508W) mutation probably represents a mutational hot-spot in Chinese HLCS deficiency patients while the 780delG mutation which was reported only in Japanese patients was found firstly in Chinese patients. PMID- 17274882 TI - [Difference in ex vivo expansion of megakaryocytes derived from umbilical cord blood and peripheral blood]. AB - OBJECTIVE: Currently, thrombocytopenia is typically observed in patients undergoing hematopioetic stem cell transplantation (HSCT), high-dose chemotherapy or irradiation. Severe thrombocytopenia can cause intestinal and intracranial hemorrhage. To transfuse ex vivo-expanded megakaryocytes (MK) into patients can reinforce the ability of platelet formation and shorten the time of platelet recovery. Therefore it is one of the effective approaches to reduce the danger. The purpose of the present study was to explore the differences in MK expansion between CD(34)(+) stem cells derived from umbilical cord blood (CB) and peripheral blood (PB) and to establish the most optimal culture system. METHODS: Mononuclear cells were isolated by density gradient centrifugation over Ficoll Hypaque gradient solution. CD(34)(+) cells were isolated by positive selection using an immunomagnetic separation system and the selected CD(34)(+) cells were seeded in Iscove's modified Dulbecco's medium (IMDM) supplemented with fetal calf serum (FCS) and certain kinds of cytokines. After 15 - 17 days of culture, the cells were counted and the content of CD(41)(+) cells was determined by using flow cytometry, and the number of megakaryocyte colony-forming unit (CFU-MK) was simultaneously measured. RESULTS: After the defined days of culture, the cytokine combination of thrombopoietin (TPO) + fetal liver tyrosine kinase ligand (FL) + IL-6 + IL-3 showed to be the most suitable for both PB and CB to obtain high numbers of MK, and to be better than any of the other three groups (P < 0.05). The CD(41)(+) cells from CB were expanded by193 +/- 25 fold on day 14, and those from PB were expanded by 131 +/- 18 fold on day 10. The number of CD(41)(+) cells from both CB and PB decreased. CONCLUSION: For PB and CB, the cytokine combination of TPO + FL + IL-6 + IL-3 is most suitable for obtaining large number of MK and is the best combination for ex vivo MK expansion. MKs from CB seemed to have higher proliferation potential than that from PB, and the optimal culture duration of MK from PB is shorter than that of MK from CB. PMID- 17274883 TI - [Clinical study on pulse transit time as a measure of sleep disordered breathing and microarousal in children]. PMID- 17274884 TI - [Polymorphism of angiotensin converting enzyme genes in children with obstructive sleep apnea-syndrome]. PMID- 17274885 TI - [Expression of myocardial thyroxin receptor mRNA in neonatal rats with hypothyroidism]. PMID- 17274887 TI - [Requirements for English abstracts of pediatric original articles (XI)]. PMID- 17274886 TI - [Suggestion of diagnosis and treatment of acute myelocytic leukemia in childhood]. PMID- 17274890 TI - [Utilities of magnetic resonance imaging in the diagnosis of cardiovascular diseases]. PMID- 17274889 TI - [The current concept of aspirin resistance]. PMID- 17274891 TI - [Recommendations for prevention and treatment of multiple cardiovascular disease risk factors]. PMID- 17274892 TI - [Identification of viable myocardium delayed enhancement magnetic resonance imaging and 99Tcm-sestamibi or 18F-fluorodeoxyglucose single photon emission computed tomography]. AB - OBJECTIVE: The aim of this study was to investigate the feasibility and accuracy of delayed enhancement magnetic resonance imaging (DE-MRI) for the assessment of myocardial viability in patients with myocardial infarction in comparison with (99)Tc(m)-sestamibi (MIBI) single photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose (FDG) SPECT. Scar was defined as regionally increased MRI signal intensity 15 minutes after injection of 0.2 mmol/kg gadolinium diethylenetriamine pentaacetic acid or reduced perfusion and glucose metabolism defined by SPECT. METHODS: A total of 34 patients with myocardial infarction (29 males, 58.0 +/- 9.8 years) were imaged with MRI and SPECT. RESULTS: A total of 578 segments were analyzed. DE-MRI and SPECT identified 431 and 336 viable segments respectively and SPECT also identified 30 ischemic segments. Necrotic segments identified by DE-MRI and SPECT were 147 and 212 respectively. Sensitivity and specificity of DE-MRI in identifying segments with matched flow/metabolism defects (scar tissues) was 61.3% and 95.4%, respectively. Quantitatively assessed relative MRI infarct area correlated well with SPECT infarct size. The value of Kappa was 0.51. CONCLUSION: DE-MRI provides a good tool for differentiating viable myocardium from scar tissues and the detection accuracy is comparable between DE-MRI and SPECT. PMID- 17274894 TI - [Diagnostic value of magnetic resonance imaging for arrhythmogenic right ventricular cardiomyopathy]. AB - OBJECTIVE: To evaluate the diagnostic value of magnetic resonance imaging (MRI) for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: MRI was performed in 27 (male 21, mean age: 37.4 y, ranging from 15 - 67 y) clinically diagnosed ARVC patients according to the 1994 ARVC diagnosis criteria of WHO from Oct. 2004 to Jun. 2006. Heart chamber size, fat infiltration, local or global ventricular function, myocardium perfusion of contrast first pass and late enhancement were examined. RESULTS: Fat infiltration was found in 24 (88.89%), trabecular disarray in 17 (62.96%), significant dilated right ventricle outlet (RVOT) in 18 (66.67%), dilated RV apex in 14 (51.85%), dilated RV free wall and posterior wall in 18 (66.67%) and right atrium enlargement in 11 (40.74%) patients. Local RV dysfunction was found in 18.52% (5/27), global RV dysfunction in 70.37% (19/27) of patients with mean RV ejection fraction (EF) of 35%. Left ventricle was affected in 40.74% (11/27) of patients. Perfusion defects were found in only 10.52% (2/19) of patients. Positive late enhancement of myocardium were found in 36.84% (7/19) of patients and affecting mainly the wall of RVOT and the free wall associated with lateral wall enhancement of LV. Five patients received heart transplantation and histology on transplanted hearts confirmed the MRI findings. CONCLUSION: "One-stop-shop" MRI scanning can be used for the diagnosis of ARVC. While for some ARVC cases with dominant abnormality in LV, it is difficult for MRI to differentiate ARVC from dilated cardiomyopathy or coronary heart disease. We found fibrosis of lateral wall of LV can be a characteristic sign of ARVC. PMID- 17274895 TI - [Clinical characterizations of patients with isolated left ventricular noncompaction diagnosed by magnetic resonance imaging]. AB - OBJECTIVE: To observe the clinical and magnetic resonance imaging (MRI) characterizations in patients with isolated left ventricular noncompaction (LVNC). METHODS: All patients were examined by MRI. The LV was divided into 9 segments for localizing non compacted segments. A new value, C/VS, was introduced to assess the degree of non compacted segments. RESULTS: A total of 31 patients was diagnosed as LVNC (23 males; 39.9 +/- 15.7 years). Palpitations presented in 74% of patients, abnormal EKG found in 93.5% of patients, 33.3% segments were affected and most commonly in the mid-ventricular and apical segments, 84% of patients had > or = 2 affected segments. Right ventricle was affected in 2 patients. Left ventricular thrombi were detected in 3 patients. LVEF was 37.2% +/ 16.5% (14% - 70%), N/C was 3.6 +/- 1.4 (2.2 - 9.2) and C/VS was 0.43 +/- 0.11 (0.27 - 0.69). CONCLUSIONS: Cardiac MRI allows accurate LVNC assessment. PMID- 17274896 TI - [Assessment left and right ventricular functions by cine magnetic resonance imaging in healthy volunteers]. AB - OBJECTIVE: Left and right ventricular functions were assessed by cine MR imaging in comparison with echocardiography in healthy volunteers. METHODS: A total of 36 healthy volunteers were examined with breath-hold true FISP cine MR imaging sequence and amended localize methods for left and right ventricular functions. Echocardiography (echo) was also performed in these volunteers. RESULTS: (1) left ventricular global function parameters obtained by MR were as follows: EDV (101.3 +/- 19.2) ml, ESV (42.1 +/- 13.3) ml, SV (69.2 +/- 9.8) ml, EF (59.1 +/- 7.2)%; Right ventricular global function as follows: EDV (118.9 +/- 27.1) ml, ESV (57.6 +/- 16.1) ml, SV (61.2 +/- 12.7) ml, EF (51.9 +/- 4.5)%. (2) EDV measured by MR and echo was similar and ESV measured by MR was significantly higher and the rest parameters were lower than that by echo. There was a good correlation (r = 0.66 - 0.80, P < 0.05) on all parameters obtained by MR and echo. CONCLUSION: The present study suggests that cine MR imaging is well applicable to left and right ventricular function and RV volume measurements. PMID- 17274897 TI - [Short-term and long-term outcomes of treating bifurcation lesions with two drug eluting stent techniques]. AB - OBJECTIVE: To evaluate the clinical outcomes of treating bifurcation lesions with two drug-eluting stent (DES) techniques. METHODS: From October 2003 to June 2005, 112 patients with 113 bifurcation lesions with severe stenosis at the ostium of side branch and the diameter > or = 2.50 mm were treated by two DES. Sixty-two of the bifurcation lesions were located in LAD/diagonal (54.9%), 32 in distal left main coronary arteries (28.3%), 18 in LCX/OM (15.9%) and 1 distal RCA (0.9%). Sixty-four lesions were treated with Crush technique, 27 with "T-form" stent implanting technique, 11 with modified "Y-form" stent implanting technique, 5 with kissing technique, 3 with "V-form" stent implanting technique and 3 with Culotta technique. Ninety-one Cypher or Cypher select DES stents, 74 TAXUS DES stents, 67 Firebird stents were used for 226 lesions. Final kissing balloon inflation was performed in 60 bifurcation lesions (93.7%) after 64 Crush stenting procedure. RESULTS: Success rate of PCI procedure for the bifurcation lesions was 100%. One patient developed subacute stent thrombosis and underwent successful urgent revascularization. In-hospital major adverse cardiac events (death, AMI, revascularization, MACE) rate was 0.89% (1/112). Nine months follow-up was made in all 112 patients and all patients were alive and MACE rate was 8.04% (9/112) with 1 AMI occurred during the follow-up period in 1 patient due to late thrombosis. Follow-up coronary angiography at 9 months was performed in 48 patients (42.9%) and evidenced 8 in-stent restenosis (16.7%) and 1 patient received CABG, re-PCI was performed in 5 patients. CONCLUSION: Two DES technique for the treatment of bifurcation lesions is safe and effective and short- and long-term outcomes is satisfactory. PMID- 17274899 TI - [Clinical and angiographic predictors of restenosis after bare metal stent deployment in coronary artery disease patients complicated with diabetes]. AB - OBJECTIVE: To identify the potential predictors of restenosis after bare mental stent (BMS) deployment in diabetic patients in Chinese diabetic patients. METHODS: We retrospectively analyzed all patients implanted with BMS (n = 1126 with 2376 lesions) in our department from 2002 to 2004. The multivariate logistic regression analysis was made to compare the clinical and angiographic characteristics between diabetic patients with and without restenosis. Restenosis was defined as > or = 50% diameter stenosis within the stent and 5 mm in adjacent. RESULTS: The 6-month follow-up angiograms were available in 889 out of 1126 patients (78.9%) and 151 out of 889 patients (17%) were diabetic patients. Restenosis rate in nondiabetic patients group was 21.2% and 35.9% in diabetic patients (P < 0.001). The predictors of restenosis in diabetics were reference vessel diameter (< or = 3.0 mm), length of lesion (> 15 mm) and insulin use (P < 0.05). The restenosis predicting model showed that reference vessel caliber was the paramount predictor for restenosis in diabetic patients. CONCLUSIONS: Restenosis rate post BMS implantation is significantly higher in diabetic patients compared to non-diabetic patients. Vessel caliber, lesion length and insulin use are predictors of restenosis in diabetic patients. Diabetic patients with reference vessel diameter of > 3.0 mm combined with lesion length < 15 mm and non-diabetic patients with lesion length < 15 mm regardless of the vessel caliber could be treated with BMS since the predicted restenosis rate is lower than 15% in these patients, otherwise DES would be a better choice. PMID- 17274900 TI - [Effects of antidepressant therapy in patients with suspected "angina pectoris" and negative coronary angiogram complicating comorbid depression]. AB - OBJECTIVE: We observed the therapeutic effectiveness and safety of different antidepressants as well as the correlation between symptomatic improvement of depression and improvement of chest pain in patients with susceptible "angina pectoris" and negative coronary angiogram complicating comorbid depression. METHODS: In this double-blinded randomized study, a total of 123 eligible patients were allocated into three groups: (1) Group F: fluoxetine 20 mg QN (n = 41); (2) Group P: Placebo 1 tablet QN (n = 40); (3) Group F + O: fluoxetine 20 mg + olanzapine 2.5 mg QN for the former 2 weeks and only fluoxetine 20 mg QN for the latter 2 weeks (n = 42). The total therapy duration was 4 weeks. HAMD, HAMA and self-evaluation table of chest pain were obtained before therapy, at the end of 1 and 2 weeks after therapy. RESULTS: Baseline HAMD and HAMA scores and self evaluation score of chest pain were similar among 3 groups and all scores were significantly improved post various therapies in the order of group F + O > group F > group P. The rate of score decrease were seen after 1 week treatment in group F + O and after 2 week treatment in group F. There was a significant positive correlation between the rates of self-evaluation chest pain score decrease and HAMD (r = 0.867, P < 0.001) and HAMA (r = 0.854, P < 0.001) score decreases after 4 weeks therapies (P < 0.05). During the whole course of treatment, no serious adverse reaction was found in all patients. CONCLUSION: In patients with suspected "angina pectoris" and negative coronary angiogram complicating comorbid depression, the antidepressants were safe and significantly improved the symptoms of depression and anxiety and chest pain. Low dose fluoxetine plus short term olanzapine regimen was superior to fluoxetine alone regimen in terms of stronger and quicker symptom improvement. PMID- 17274901 TI - [A novel polymorphism in the ATP-binding cassette transporter A1 gene (M233V) in Chinese patients with coronary artery disease]. AB - OBJECTIVE: To identify ATP-binding cassette transporter A1 (ABCA1) gene polymorphism in Chinese patients with coronary artery disease (CAD). METHODS: Single Nucleotide Polymorphisms in the ABCA1 gene were detected by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP)-DNA sequence and restriction-fragment length polymorphism (RFLP) method in 112 patients with CAD. RESULTS: A novel polymorphism in the ABCA1 gene was found in two patients: M233V which exists in exon7 of ABCA1 gene and it's cDNA location is A1092G and converse 233 amino acid from Methionine to Valeric. We further collected the blood samples from 16 family members of one proband and M233V polymorphism was found in 5 out 16 family members. CONCLUSION: M233V is a novel polymorphism in the ATP-binding cassette transporter A1 gene and this AG genotype had family proneness. PMID- 17274902 TI - [The safety and efficacy of basiliximab as induction agent in preventing early acute rejection in Chinese cardiac transplantation receipts]. AB - OBJECTIVE: To investigate the safety and efficacy of basiliximab as induction agent in preventing early acute rejection post heart transplantation. METHODS: Basiliximab (20 mg, iv) was administered one hour before and 4 days post operation to patients (n = 47) underwent heart transplantation between June 2004 and Feb 2005 in our department. Intravenous methylprednisolone (500 mg at operation beginning and repeated immediately post operation, followed by 125 mg every 8 hours for the first day). Prednisone was then initiated at 1 mg.kg(-1).d( 1) tapered 10 mg every 3 days to 10 mg/d. Mycophenolate mofetil (MMF, 0.5 - 1.0 g twice daily) was also administered post intubation, oral Cyclosporine A (CsA, 3 to 6 mg.kg(-1).d(-1)) was prescribed after transplantation if serum creatinine was < 150 micromol/L. The dose of CsA was individually adjusted to achieve a target serum concentration of 180 - 300 ng/ml. Endomyocardial biopsies were performed 3 weeks (19.7 +/- 9.6) d post heart transplantation. Biopsy specimens were graded according to the standardized criteria of the International Society for Heart and Lung Transplantation (ISHLT). Echocardiograms were routinely performed weekly within the first 3 weeks post-operation. RESULTS: All 47 consecutive patients [mean age (44.9 +/- 13.4) years, range 13 - 63 years, 38 men] survived the operation and the underlying diseases was idiopathic cardiomyopathy (42.5%), ischemic heart disease (25.5%), arrhythmogenic right ventricular cardiomyopathy (17.0%), hypertrophic cardiomyopathy (4.2%), heart tumor (4.25%), valve heart disease (2.1%), hypertensive cardiomyopathy (2.1%) and giant cell myocarditis (2.1%). There were 4 patients with pre-operation PRA > 10% and CDC was less than 5% in all patients. The grades of the acute rejection in biopsy specimens were as follow: Grade (G) 0 in 30 (63.8%), G IA in 11 (23.4%), G IB in 3 (6.3%) and GII in 3 (6.3%) patients. The average dose of MMF was (1.2 +/- 0.3) g/d. The initial time of receiving CsA was (3.4 +/- 2.1) day post operation. The average cumulative dose of CsA was (4.1 +/- 1.2) mg.kg(-1).d(-1) before endomyocardial biopsy. The average serum concentration of CsA was (237.0 +/- 76.2) ng/ml. Left ventricular ejection fraction assessed by echocardiogram was normal in all patients within the first 3 weeks. Five patients suffered from respiratory infections and recovered post antibiotic and symptomatic therapies. CONCLUSION: Basiliximab as induction agent in combination with conventional triple immunosuppressive therapy is safe and effective in preventing acute rejection in Chinese cardiac transplantation receipts. PMID- 17274905 TI - [Fosinopril but not metoprolol attenuated the increased matrix metallo proteinases 9 expression at mRNA and protein levels of human umbilical vein endothelial cells exposed to oscillatory flow]. AB - OBJECTIVE: To investigate the effect of fosinopril and metoprolol on metalloproteinases 9 (MMP9) expression of human umbilical vein endothelial cells (HUVECs) stimulated by oscillatory flow. METHODS: HUVECs were exposed to steady laminar flow or oscillatory flow, laminar flow or oscillatory flow plus various concentrations (1 x 10(-7) mol/L, 1 x 10(-5) mol/L) of fosinopril and metoprolol for 4 and 24 hours. MMP9 mRNA and protein expressions of HUVECs were determined by RT-PCR and Western blot, respectively. RESULTS: MMP9 expression at mRNA and protein levels were significantly increased in HUVECs exposed to oscillatory flow than that to laminar flow and these could be down-regulated by coincubation with fosinopril (1 x 10(-7) mol/L, 1 x 10(-5) mol/L, P < 0.01, P < 0.05, respectively) but not by co-incubation with metoprolol. CONCLUSION: Fosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow. PMID- 17274906 TI - [Effects of C-reactive protein and tumor necrosis factor-alpha on mRNA expression of pregnancy-associated plasma protein-A in monocytes]. AB - OBJECTIVE: Serum pregnancy-associated plasma protein A (PAPP-A) is increased in acute coronary syndrome patients and related to prognosis. We investigated the effects of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) on PAPP-A mRNA expression in monocytes. METHODS: Monocytes were isolated by Ficoll density gradient centrifugation from blood of healthy volunteers. The PAPP A expressions at mRNA level post CRP or rhTNF-alpha stimulation were measured by RT-PCR. RESULTS: PAPP-A mRNA expression in peripheral blood monocytes increased 2 hours (0.2128 +/- 0.0136) and peaked 24 hours (0.6837 +/- 0.1360) after CRP (20 mg/L) stimulation compared with control group (0.1842 +/- 0.0101). PAPP-A mRNA expression increased rapidly, peaked 2 hours (1.2546 +/- 0.0866) and remained elevated up to 24 hours (0.8203 +/- 0.0413) after rhTNF-alpha (100 ng/ml) stimulation. The effects of CRP and TNF-alpha were dose-dependent. PAPP-A mRNA expression of monocytes were 0.2544 +/- 0.0611, 0.4177 +/- 0.1200, 0.5828 +/- 0.0152, 0.6837 +/- 0.1360 after stimulated with CRP (1, 5, 10, 20 mg/L), and 0.2424 +/- 0.1378, 0.3335 +/- 0.0196, 0.5742 +/- 0.0131, 0.6913 +/- 0.0219 and 0.8203 +/- 0.0413 after stimulated with rhTNF-alpha (5, 10, 25, 50 and 100 ng/ml). Actinomycin D, the DNA-directed RNA polymerase inhibitor, completely blocked CRP and TNF-alpha induced PAPP-A expression. CONCLUSIONS: PAPP-A mRNA expression could be stimulated by CRP and TNF-alpha in human peripheral blood monocytes which might be responsible for the increased serum PAPP-A level in patients with acute coronary syndromes. PMID- 17274909 TI - [Recombinant plasmid pIRES2-EGFP-HCN2 improved pacing function in canine model of sick sinus syndrome]. AB - OBJECTIVE: To construct plasmid expressing pacemaker gene pIRES2-EGFP-HCN2 and study its effects in transfected atrial myocytes in vitro and in canine model of sick sinus syndrome (SSS). METHODS: mHCN2 gene was isolated from PTR plasmids and cloned into eukaryotic expression plasmid pIRES2-EGFP. Recombinant plasmids pIRES2-EGFP-HCN2 was transfected with by electroporation into neonatal atrial cardiomyocytes or injected to the sinoatrial (SA) region of canines with SSS induced by catheter and chemical ablation. pIRES2-EGFP-HCN2 expression was detected under fluorescence microscope and confirmed by reverse transcription polymerase chain reaction (RT-PCR). Spontaneous beating rate in atrial cardiomyocytes was detected with light microscope. RESULTS: EGFP expression was seen in transfected atrial cardiomyocytes 24 to 48 hours after transfection and the spontaneous beating rate was significantly increased than that in non transfected atrial cardiomyocytes [(180 +/- 11) bpm vs (140 +/- 14) bpm, P < 0.05]. Heart rate was significantly increased 24 hours post recombinant plasmids pIRES2-EGFP-HCN2 injection compared to saline injection in canines with SSS [(150 +/- 13) bpm vs (105 +/- 17) bpm, P < 0.05]. Green fluorescence was also detected in frozen SA tissue sections of canines injected with recombinant plasmids pIRES2 EGFP-HCN2 and the production amplified by RT-PCR was about 300 bp which is consistent with mHCN2 gene fragment. CONCLUSION: The recombinant eukaryotic expression plasmid pIRES2-EGFP-HCN2 can improve pacing function in atrial myocytes and in canine model of SSS. PMID- 17274908 TI - [Effects of recombinant adenovirus encoding human apM1 gene on proliferation and nitric oxide synthase activity in human umbilical vein endothelial cells]. AB - OBJECTIVE: To evaluate the effects of recombinant adenovirus encoding human apM1 gene on proliferation and nitric oxide synthase (NOS) activity in human umbilical vein endothelial cells (HUVECs). METHODS: Protein expression of apM1 in cell culture supernatant of HUVECs transfected with human Ad-apM1 was detected by double antibody sandwich ELISA. The effect of human adiponectin on cell proliferation was assessed by MTT assay. The total NOS and iNOS expressions were measured by chromatometre. RESULTS: Human adiponectin protein level and total NOS and eNOS expressions were significant increased and iNOS expression significantly reduced in culture supernatant of HUVECs infected with Ad-apM1 compared to that in control HUVECs. The recombinant adenovirus had no influence on HUVECs growth as determined by MTT assay. CONCLUSIONS: Human Ad-apM1 can be effectively expressed in HUVECs and do not influence HUVECs growth. Increased total NOS and eNOS expressions and decreased iNOS expression in HUVECs transfected with Ad-apM1 gene suggest a potential role of Ad-apM1 gene transfer for the prevention and treatment of arteriosclerosis. PMID- 17274917 TI - [Current opinions of late reperfusion therapy after myocardial infarction]. PMID- 17274911 TI - [Risk factors comparison in Chinese patients developing acute coronary syndrome, ischemic or hemorrhagic stroke: a multi-provincial cohort study]. AB - OBJECTIVE: To observe the risk factors characteristic of patients developing acute coronary syndrome, ischemic or hemorrhagic stroke in a Chinese population aged 35 - 64 (n = 30 378). METHOD: This prospective study was carried out in 11 provinces in China from 1992 to 2003. The association between baseline risk factors and events in the 10-year follow-up period was analyzed. RESULTS: (1) A total of 809 events were recorded during the follow up period and 227 with acute coronary syndrome, 582 with stroke (ischemic 419, hemorrhagic 146, undefined 17) and the 10-year cumulative person-year incidence rates were 114/100,000, 209/100,000 and 73/100,000 for acute coronary syndrome, acute ischemic stroke and acute hemorrhagic stroke, respectively. (2) Rate of having > or = 1 modifiable risk factors was significantly higher in event group than that in subjects without events (89% vs. 64.7%, P < 0.01). (3) Sorted by intensity, the sequence of independently risk factors obtained from multivariate analysis for acute coronary syndrome were hypertension, smoking, hypercholesterolemia and low-HDL-C; for acute ischemic stroke event were hypertension, diabetes, low-HDL-C, smoking and obesity; for acute hemorrhagic stroke was hypertension. CONCLUSION: The morbidity for cardiovascular diseases is higher in Chinese population with various traditional risk factors than those without or having fewer traditional risk factors and there are various distinct independent risk factors pattern in patients with different cardiovascular diseases subtypes. PMID- 17274920 TI - [The new asylums]. PMID- 17274921 TI - [Future endocrine therapy of breast cancer]. PMID- 17274922 TI - [Adjuvant antihormonal therapy for postmenopausal women with primary operable breast cancer]. AB - Adjuvant hormonal therapy results in substantial improvements in disease-free and overall survival for women with operable breast cancer. Many randomised trials of adjuvant tamoxifen have been published, and an updated overview of their results is presented in this paper. The third-generation aromatase inhibitors have recently been compared with tamoxifen. These studies are also reviewed in this paper. The Danish Breast Cancer Cooperative Group recommends adjuvant hormonal therapy consisting of tamoxifen for 2.5 years followed by the aromatase inhibitor for 2.5 years, or 5 years of the aromatase inhibitor for women with contraindications to tamoxifen. PMID- 17274924 TI - [A clinical gait analysis. A survey of usefulness of a gait laboratory]. AB - Advanced equipment for objective, quantitative 3-D locomotion analysis has been developed and has resulted in setting up clinical gait and locomotion laboratories connected to hospitals in USA and Europe. Before treatment of sufferings related to the locomotive system, the pathological movements can be objectified, and by repeating a gait analysis, the effect of treatment can be read. In treatment of cerebral palsy the method is used routinely, but influences of traumatic brain damage and apoplexy, as well as the effect of artificial joints in the body's locomotive patterns, can profitably be analysed. PMID- 17274923 TI - [Auto-antibodies against glutamic acid decarboxylase and diabetes]. AB - The 1999 WHO classification delineates immune mediated type 1 diabetes from other types of diabetes by the presence of auto-antibodies against beta-cell constituents. The GAD65 auto-antibody test is the method of first choice because it has the highest sensitivity, specificity and positive predictive value and is the most standardized and well-characterized type 1 diabetes related auto antibody analysis. It is recommended that demonstration of GAD auto-antibodies leads to diagnosis, classification or re-classification of diabetes patients as immune mediated type 1 diabetes. PMID- 17274925 TI - [Residents in the psychiatric institution Sundbygard. Comparison of two cross sectional studies, from 1998 and 2004]. AB - INTRODUCTION: The deinstitutionalization of psychiatric hospitals has triggered a development of social institutions for mentally ill persons. In 1987 the psychiatric institution Sundbygard was changed for this purpose, and in 2001 enlarged. A survey in 1998 showed that the residents were mainly people suffering from schizophrenia with need for intensive psychiatric treatment. The usage of psychiatric hospital beds for residents increased from an average of 7.7 beds per day in 1998 to 10.2 beds in 2003. It was necessary to repeat the survey from 1998, this time adding an analysis of predictive factors for readmission to psychiatric ward. In the following, we will present the results of such an analysis. METHODS: The psychiatrist in charge of treatment evaluated the residents by the same methods as used in 1998 for demographic and clinical information in cooperation with the staff. While in 1998 there were 78 male and 69 female residents, in 2004 there were 90 males and 76 females. RESULTS: The median age of the residents declined from 1998 to 2004. The proportion of schizophrenics increased from 69 to 90%. Similar results were seen for alcohol and drug abusers, with an increase from 16 to 26%. Residents with forensic psychiatric sentences increased from 5 to 12 and residents with severe productive symptoms increased from 47 to 97. The median GAF score was 35. In 2004 the atypical antipsychotics were generally prescribed. Predictors for readmission to psychiatric ward were new residency, forensic psychiatric sentence and severity of productive symptoms. CONCLUSION: This study shows that from 1998 to 2004 the number and proportion of residents with a schizophrenia diagnosis and an active alcohol and drug abuse has increased. The need for psychiatric admissions also increased. Thus, reallocation of resources is needed. PMID- 17274926 TI - [Stress in families with children: are children the cause?]. AB - INTRODUCTION: Stress may affect health negatively. Therefore, it is important to identify risks factors for high levels of stress. Previous studies indicate that parents report higher levels of stress than adults without children. Whether this it due to having children or due to other circumstances is unknown. The purpose of this study is to investigate whether parents have higher levels of stress than adults without children after controlling for possible confounders. A possible interaction between being a parent and working time on perceived stress will be examined. METHODS: Cross-sectional data from Danish Health and Morbidity Survey 2000 were used. 3,083 men and 2,813 women aged 25-49 years answered one question on perceived stress. All analyses were stratified on sex and marital status and adjusted for age, socio-economic level, income and work hours/week. RESULTS: No differences in perceived stress between men and women with and without children were found. Women, who were lone parents and worked more than 37 hours a week, had a markedly increased level of stress (OR: 3.2, 95%CI: (1.3-7.8)) compared to single women without children working 37 hours a week. CONCLUSION: Children in the household did not appear to be the cause of a high level of perceived stress. Single mothers with long working hours were an exception to this conclusion. PMID- 17274927 TI - [Infusion pumps and patient safety]. AB - INTRODUCTION: Infusion pumps are important clinical tools where controlled and precise infusions are needed. However, there are a number of potential risks for patient safety in their use: There is a risk of free-flow, i.e. an uncontrolled infusion that may have fatal consequences to the patient; staff is often poorly trained to use these devices, and often the devices themselves do not offer much support in this regard. MATERIAL AND METHODS: Technical and organisational data regarding the use of infusion pumps in the hospitals of the Copenhagen Hospital Corporation (CHC) were collected and analysed. Critical incidents reported to the CHC Incident Database were analysed. RESULTS: Forty-two different infusion pumps are in use by the five CHC hospitals. There was a total of 919 volumetric infusion pumps, 71% having set-based free-flow protection. Critical incidents were in 40% of cases caused by user-error, the most common being setting an incorrect infusion rate. Discontinuation of the infusion was reported in 27% of incident reports, the causes being disconnection or kinking of the infusion line; this resulted in two cases of awareness under anaesthesia. CONCLUSION: Centralising the decision process for procurement and establishing a central library of standardised equipment might well reduce patient safety risks and any under-use of equipment. Usability testing prior to procurement decisions is vital; such testing should be performed by validated methods and not simply by putting the pumps to test in a clinical setting. More knowledge about user friendly designs of medical equipment is needed. PMID- 17274928 TI - [A ten-year retrospective study of patients operated for hypospadias]. AB - INTRODUCTION: Retrospectively we evaluated the surgical treatment of all primary operations for hypospadias performed at the Department of Plastic- and Reconstructive Surgery, Herlev University Hospital, over a period of ten years. During this time we changed the concept of surgical procedure from various two stage techniques to a new one-stage modification (Scuderi's vascularised vertical preputial island flap combined with a triangular flap glanuloplasty and other refinements). Secondly, we evaluated the pre- and postoperative examination. MATERIALS AND METHODS: During the period 1993-2003, 96 patients were primarily operated. The new one-stage technique was used in 58 patients, all performed by the same surgeon. The standardised follow-up time was three months. RESULTS: Complications consisted of five urethrocutaneous fistulas (8.6%) and four meatal stenosis (6.7%), and the functional and cosmetic short-term outcome was satisfactory using the new one-stage procedure. The number of operations per patient was reduced from 4.57 to 1.26. We found the pre- and postoperative examination inadequate concerning classification of hypospadias type and possible associated malformations (cryptorchidism). CONCLUSION: The short-term functional and cosmetic outcome of the new one-stage technique was satisfactory. The complication rate was low. However, the study was associated with severe methodological problems. On this background we suggest a national standardised registration of all boys operated for hypospadias. PMID- 17274929 TI - [Acute mesenteric ischaemia in a patient with Crohn's disease]. AB - A 48-year-old patient known to have Crohn's disease (diagnosis verified by clinical findings, histology and colonoscopy) was admitted to the hospital with acute abdominal pain. Additional examination did not suggest another pathology. Acute mesenteric ischaemia was suspected late and diagnosed only during laparotomy. CT scan and MR were normal, but abdominal angiography confirmed total occlusion of the superior mesenteric artery. In this case the outcome was death. PMID- 17274930 TI - [Infectious monoarthritis in the subtalarian joint due to N. gonorrhoae]. AB - We report a case of gonococcal monoarthritis in the ankle of a young female. A blind tap of synovial fluid from the talocrural joint was without bacterial growth. The patient received anti-inflammatory treatment but did not improve. In an ultrasound-guided puncture of the subtalarian joint, the synovial fluid culture revealed N. gonorrhoeae. Due to the increasing incidence of gonorrhoea in Denmark, gonococcal monoarthritis should be suspected in any case of monoarthritis in young, sexually active patients. If small joints are affected, ultrasound-guided puncture is recommended to ensure correct microbiological diagnosis. PMID- 17274931 TI - [Picture of the month: intestinal hemorrhage]. PMID- 17274932 TI - Socioeconomic status and the prevalence of melanoma in Ontario, Canada. AB - OBJECTIVE: To determine if an association exists between the prevalence of melanoma and socioeconomic status based on income gradients in a large population of over 12 million people in Ontario, Canada. METHODS: A population-based cross sectional study using administrative health care databases was conducted. Individuals were divided into five income quintiles based on median neighborhood household income. A Mantel-Haenszel extension test was used to assess whether there was a gradient in the prevalence of melanoma across income groups. Multivariate logistic regression was used to determine if median neighborhood income predicted the prevalence of a melanoma, independent of gender, age, and urban-rural residence status. RESULTS: The study cohort consisted of 14,623 patients with melanoma. Between the lowest income group of $37,637 and the highest income group of $84,162, the prevalence of melanoma increased by 225%. Our study also identified an association between melanoma prevalence and rural residence. The overall prevalence rate was 30% (p < .01) higher in rural areas compared with urban areas. CONCLUSION: A higher socioeconomic status and rural versus urban residence status appear to be significant risk factors for the development of melanoma in Ontario. PMID- 17274933 TI - Surgical treatment of facial cutis verticis gyrata with direct excision. AB - BACKGROUND: Cutis verticis gyrata (CVG) is a rare deformity of the skin presenting with thick gyrated folds and ridges, involving predominantly parts of the head and the face. OBJECTIVE: We report on aspects of the surgical treatment of facial CVG based on our experiences with four patients, who had developed a progressive and enormous thickening and an extraordinary strong gyration of the facial skin. METHODS: A single or staged repeated straightforward surgical treatment with direct excision of abundant and thickened gyriform folds, in one case accomplished by an upper face-lift, was performed. RESULTS: Direct excision within the lines of tension resulted in a major reduction of the facial skin distortion, a reduced scalp, and facial skin thickening and avoided maceration in all four patients. The quality of life was considerably improved in all patients. CONCLUSION: Direct excision of gyriform skin is a successful surgical approach to the rare skin deformity of CVG. PMID- 17274935 TI - Basal cell carcinoma: review of epidemiology, pathogenesis, and associated risk factors. AB - BACKGROUND: Basal cell carcinoma (BCC) is extremely common, and its incidence continues to rise. OBJECTIVE: This review presents the literature pertaining to the epidemiology, pathogenesis, and risk factors associated with BCC. CONCLUSIONS: The risk of developing BCC depends on both genetic predisposition and exposure to risk. Fair-skinned people account for the overwhelming majority of patients, beyond what would be expected by skin phototype alone. Damage to multiple lines of defense appears to be necessary for cancer development and spread. This damage distorts the concerted effort of deoxyribonucleic acid (DNA) repair, immunosurveillance, and cellular growth regulation to protect against malignant progression. Ultraviolet light exposure is the most critical modifiable factor determining early expression and frequency of BCC development. PMID- 17274934 TI - Weight of decision-making impairs clinical assessment of melanocytic lesions. AB - BACKGROUND AND OBJECTIVE: We studied the weight of decision-making on clinical assessment of melanocytic lesions judging benign, atypical, and malignant lesions; common mistakes; and total removal rates, comparing dermatologists with nondermatologists. METHODS: Of 11,246 histopathology specimens, 3,768 had a clinical assessment of melanocytic lesions. Histopathologic diagnosis served as the gold standard. RESULTS: Benign nevi were assessed most accurately (77%). Dermatologists assessed benign nevi better (p < .0001). The accuracy of clinical assessment in atypical nevi and melanoma was lower (23% and 42%, respectively). Seborrheic keratosis was the most common mistaken diagnosis. Complete removal of clinically benign nevi, atypical nevi, and melanoma was 84%, 90%, and 89%. Decision-making impaired clinical assessement of melanocytic lesions by 5% for dermatologists and 9% for nondermatologists. CONCLUSION: The accuracy of clinical assessment of melanocytic lesions is high for benign nevi, with dermatologists outperforming nondermatologists. Clinicians overestimated malignant potential. Complete removal was more frequent in suspicious lesions. Clinical decision making impaired assessment by 5 to 9%. PMID- 17274936 TI - Miliarial gout (a new entity). AB - BACKGROUND: Tophaceous gout typically presents as a subcutaneous, nodular collection of monosodium urate crystals sharply circumscribed from surrounding tissues. Although intradermal cutaneous manifestations of gout have been described, no reported cases of miliarial gout remain. OBJECTIVE: We describe the first known presentation of miliarial gout and list other uncommon cutaneous manifestations of gouty tophi. The treatment of miliarial gout is discussed, as well as risk factors predisposing an individual to the development of intradermal tophi. RESULTS: Miliarial gout is an intradermal phenomenon consisting of multiple tiny papules containing material of a white to cream color scattered on an erythematous base that responds to allopurinol administration. Risk factors predisposing an individual to the development of intradermal gout include renal insufficiency, hypertension, chronic diuretic therapy, long duration of disease, and lack of consistent use of urate-lowering therapy. CONCLUSION: Miliarial gout is a unique intradermal manifestation of tophaceous gout. PMID- 17274937 TI - Perifolliculitis capitis abscedens et suffodiens in an 18-year-old Aboriginal Canadian patient: case report and review of the literature. AB - BACKGROUND: Perifolliculitis capitis abscedens et suffodiens (PCAS) is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. This condition often presents in males of African American origin. OBJECTIVE: This article describes the clinical presentation, diagnosis, and treatment of an Aboriginal Canadian male suffering from PCAS. A literature review on the etiology, pathology, differential diagnosis, and management is also discussed. CONCLUSION: Careful analysis of the pathology and clinical presentation can aid in the timely diagnosis and management of this challenging condition. The clinician dealing with patients suffering from PCAS has several treatment options available to help successfully manage patients with straightforward or recalcitrant disease. PMID- 17274938 TI - Multilevel modelling for the regional effect of enforcement on road accidents. AB - This paper investigates the effect of the intensification of Police enforcement on the number of road accidents at national and regional level in Greece, focusing on one of the most important road safety violations: drinking-and driving. Multilevel negative binomial models are developed to describe the effect of the intensification of alcohol enforcement on the reduction of road accidents in different regions of Greece. Moreover, two approaches are explored as far as regional clustering is concerned: the first one concerns an ad hoc geographical clustering and the second one is based on the results of mathematical cluster analysis through demographic, transport and road safety characteristics. Results indicate that there are significant spatial dependences among road accidents and enforcement. Additionally, it is shown that these dependences are more efficiently interpreted when regions are determined on the basis of qualitative similarities than on the basis of geographical adjacency. PMID- 17274939 TI - Alcohols induce beta-hematin formation via the dissociation of aggregated heme and reduction in interfacial tension of the solution. AB - The formation of the malarial pigment, a unique hemozoin crystal with unit cells comprised of heme dimers, has been proposed as an ideal target for antimalarial screening. The mechanism of beta-hematin formation (a synthetic crystal structurally identical to hemozoin) has been suggested that a hydrophobic interaction is needed to solubilize heme, but this hypothesis needs further evidence. Direct study of the process of hemozoin formation in the malarial food vacuole has not been performed, due to complicated groups of lipids and proteins. To overcome this difficulty and to explore the environmental conditions for beta hematin formation, we systematically studied beta-hematin formation induced by a series of small normal alcohols (methanol, ethanol, n-propanol, and n-butanol), which are structurally similar. For the first time, the ability of beta-hematin inducer could be evaluated by its concentration that is required to enhance heme crystallization by 50% (EC(50) values). These values provide a rapid and convenient tool for comparing the ability of initiators in beta-hematin formation. Our results showed that the ability of alcohols to induce beta-hematin formation in the order: n-butanol>n-propanol>ethanol>methanol. The induction of beta-hematin formation by alcohols is related with their degree of hydrophobicity and ability to solubilize heme, suggesting that the dissociation of aggregated heme by alcohols is a major factor in beta-hematin formation. In addition, alcohols can reduce the surface tension of a solution, thus lowering the energy barrier for creating critical nuclei. PMID- 17274940 TI - Surface-plasmon-resonance-based biosensor with immobilized bisubstrate analog inhibitor for the determination of affinities of ATP- and protein-competitive ligands of cAMP-dependent protein kinase. AB - Interactions between adenosine-oligoarginine conjugates (ARC), bisubstrate analog inhibitors of protein kinases, and catalytic subunits of cAMP-dependent protein kinase (cAPK Calpha) were characterized with surface-plasmon-resonance-based biosensors. ARC-704 bound to the immobilized kinase with subnanomolar affinity. The immobilization of ARC-704 to the chip surface via streptavidin-biotin complex yielded a high-affinity surface (K(D)=16nM). The bisubstrate character of ARC-704 was demonstrated with various ligands targeted to ATP-binding pocket (ATP and inhibitors H89 and H1152P) and protein-substrate-binding domain of Calpha (RIIalpha and GST-PKIalpha) in competition assays. The experiments performed on surfaces with different immobilization levels of ARC-704 produced similar results. The closeness of the obtained affinities of the tested compounds to the inhibitory potencies and affinities of the compounds measured with other methods demonstrates the applicability of the chip with the immobilized biligand inhibitor for the characterization of both ATP- and substrate protein-competitive ligands of basophilic protein kinases. PMID- 17274941 TI - Characterization of dual-wavelength seminaphthofluorescein and seminapthorhodafluor dyes for pH sensing under high hydrostatic pressures. AB - Hydrostatic pressure is an important physical parameter in biology, with pressures in the few-hundred-atm range having significant effects on cellular morphology, metabolism, and viability. To ensure valid results when studying pressure effects using fluorescence spectroscopy and imaging methods, metabolic probes need to be characterized for high-pressure use. Of interest is the sensing of pH at high pressures due to the key role that pH plays in cellular function. Despite the availability of pH-sensitive dyes, only a few have been characterized for high-pressure use. Here we present the effects of pressure on the acid-base equilibria of four dual-wavelength seminaphthorhodafluor and seminaphthofluorescein dyes (pK(a)=6.6-7.8). Using phosphate buffers as high pressure pH references, we investigate the pressure dependence of pK(a) for these dyes and determine the volume change associated with the acid-dissociation reaction. We find that if pressure-induced pK(a) changes are not accounted for during interpretation of emission spectra, systematic errors of up to 0.02 pH units per 100atm would result, comparable to previously measured pressure-induced pH changes in vivo. Results are validated by correctly sensing pH changes in Tris and acetate solutions. Methods presented here are applicable to other metabolic probes utilizing dual-wavelength ratiometric sensing modes. PMID- 17274943 TI - Biomolecular investigation of human substantia nigra in Parkinson's disease by synchrotron radiation Fourier transform infrared microspectroscopy. AB - Synchrotron radiation based-Fourier transform infrared microspectroscopy was used for preliminary investigation of the chemical composition and morphologies of the human substantia nigra of brain between normal and Parkinson's diseased tissues. The studies were carried out for thin tissue sections, focusing more particularly on nerve cell bodies, that are affected in Parkinson's disease (PD). The major spectral differences between normal (control) and PD tissues were identified at the following vibrational frequencies: 2930, 2850, 1655, 1380, 1236, 1173 and 1086 cm(-1). The infrared imaging of these biochemical markers show that for control cases the protein and nucleic acids functional groups (bands at: approximately 3300, approximately 3100, approximately 1655, approximately 1545, approximately 1240, approximately 1080 cm(-1)) are located mainly in the cell body. The spatial distribution of the band at 1740 cm(-1) (ester carbonyl stretching band) is quite dissimilar to the others, while it exhibits a minimal concentration in the cell body area. Contrarily, in PD samples, no clear evidence of variation of any of the vibrational fingerprint between cell body and the surrounding was noticed. Moreover, decrease of protein to lipid ratio as well as increase of amide I/amide II ratio were observed for PD case. The preliminary results strengthen the hypothesis that PD is a multietiological disorder. Moreover, the reported results clearly indicate that, in addition to a distinct visual observation, the diseased nerve cells exhibits change of their biochemical composition. It suggests that disturbances of normal functioning of SN neurons appear before their morphological atrophy. PMID- 17274944 TI - Jaw-neck dysfunction in whiplash-associated disorders. AB - This paper reports data from recent studies on integrative jaw-neck motor control in healthy subjects and disturbed jaw-neck behaviour in whiplash-associated disorders (WAD). The results show that neck function is an integral part of natural jaw behaviour, and that neck injury can impair jaw function and therefore disturb eating behaviour. We also show preliminary results from implementation of a new approach for rehabilitation of jaw-neck dysfunction and pain in WAD. PMID- 17274942 TI - Role of subunit interactions in P450 oligomers in the loss of homotropic cooperativity in the cytochrome P450 3A4 mutant L211F/D214E/F304W. AB - The contribution of conformational heterogeneity to cooperativity in cytochrome P450 3A4 was investigated using the mutant L211F/D214E/F304W. Initial spectral studies revealed a loss of cooperativity of the 1-pyrenebutanol (1-PB) induced spin shift (S(50)=5.4 microM, n=1.0) but retained cooperativity of alpha naphthoflavone binding. Continuous variation (Job's titration) experiments showed the existence of two pools of enzyme with different 1-PB binding characteristics. Monitoring of 1-PB binding by fluorescence resonance energy transfer from the substrate to the heme confirmed that the high-affinity site (K(D)=0.3 microM) is retained in at least some fraction of the enzyme, although cooperativity is masked. Removal of apoprotein on a second column increased the high-spin content and restored cooperativity of 1-PB binding and of progesterone and testosterone 6beta-hydroxylation. The loss of cooperativity in the mutant is, therefore, mediated by the interaction of holo- and apo-P450 in mixed oligomers. PMID- 17274945 TI - Inhibition of respiration and nitrate assimilation enhances photohydrogen evolution under low oxygen concentrations in Synechocystis sp. PCC 6803. AB - In cyanobacterial membranes photosynthetic light reaction and respiration are intertwined. It was shown that the single hydrogenase of Synechocystis sp. PCC 6803 is connected to the light reaction. We conducted measurements of hydrogenase activity, fermentative hydrogen evolution and photohydrogen production of deletion mutants of respiratory electron transport complexes. All single, double and triple mutants of the three terminal respiratory oxidases and the ndhB-mutant without a functional complex I were studied. After activating the hydrogenase by applying anaerobic conditions in the dark hydrogen production was measured at the onset of light. Under these conditions respiratory capacity and amount of photohydrogen produced were found to be inversely correlated. Especially the absence of the quinol oxidase induced an increased hydrogenase activity and an increased production of hydrogen in the light compared to wild type cells. Our results support that the hydrogenase as well as the quinol oxidase function as electron valves under low oxygen concentrations. When the activities of photosystem II and I (PSII and PSI) are not in equilibrium or in case that the light reaction is working at a higher pace than the dark reaction, the hydrogenase is necessary to prevent an acceptor side limitation of PSI, and the quinol oxidase to prevent an overreduction of the plastoquinone pool (acceptor side of PSII). Besides oxygen, nitrate assimilation was found to be an important electron sink. Inhibition of nitrate reductase resulted in an increased fermentative hydrogen production as well as higher amounts of photohydrogen. PMID- 17274946 TI - Dopamine D3 receptor ligands: recent advances in the control of subtype selectivity and intrinsic activity. AB - Various pharmacological studies have implicated the dopamine D(3) receptor as an interesting therapeutic target in the treatment of different neurological disorders. Because of these putative therapeutic applications, D(3) receptor ligands with diverse intrinsic activities have been an active field of research in recent years. Separation of purely D(3)-mediated drug effects from effects produced by interactions with similar biogenic amine receptors allows to verify the therapeutic impact of D(3) receptors and to reduce possible side-effects caused by "promiscuous" receptor interactions. The requirement to gain control of receptor selectivity and in particular subtype selectivity has been a challenging task in rational drug discovery for quite a few years. In this review, recently developed structural classes of D(3) ligands are discussed, which cover a broad spectrum of intrinsic activities and show interesting selectivities. PMID- 17274948 TI - The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-alpha-induced apoptosis. AB - Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-alpha in combination with IFN-gamma in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-alpha-resistant B16/F10.9 melanoma cells. A low dose of TNF-alpha or IL-6/sIL-6R had minimal affect on the cell growth. However, the highly active fusion protein of sIL-6R and IL-6 (IL6RIL6), covalently linked by a flexible peptide, sensitized TNF-alpha-resistant F10.9 melanoma cells to TNF alpha-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-alpha resulted in both the activation of caspase-3 and the reduction of bcl-2 expression. Flow cytometry analysis showed that IL6RIL6-upregulated TNF-R55 and TNF-R75 expression, suggesting an increase in TNF-alpha responsiveness by IL6RIL6 resulting from the induction of TNF receptors. Moreover, exposure of F10.9 cells to neutralizing antibody to TNF-R55 significantly inhibited IL6RIL6/TNF-alpha induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-alpha-resistant melanoma cells to TNF-alpha-induced apoptosis, may provide a new target for immunotherapy. PMID- 17274947 TI - The FBXW7 beta-form is suppressed in human glioma cells. AB - FBXW7 (F-box and WD40 domain protein 7) is an F-box protein with 7 tandem WDs (tryptophan-aspartic acid) that functions as a phosphoepitope-specific substrate recognition component of SCF (Skp1-Cul1-F-box protein) ubiquitin ligases and catalyzes the ubiquitination of proteins promoting cell proliferation, such as CCNE1, MYC, AURKA, NOTCH1, and JUN, which are frequently activated in a wide range of human cancers. FBXW7 is a candidate tumor suppressor, and mutations have been reported in some human tumors. In this study, we analyzed 84 human tumor cell lines in search for genetic alterations of FBXW7, as well as mRNA and protein expressional changes, and compared them with expression levels of the CCNE1, MYC, and AURKA proteins. We found a novel nonsense mutation in a colon cancer cell line SCC and confirmed the missense mutations in SKOV3, an ovarian cancer cell line, and LoVo, a colon cancer cell line. Moreover, suppressed expression of FBXW7 accompanied by activation of the target proteins were observed in ovarian, colon, endometrial, gastric, and prostate cancers. It is notable that highly suppressed mRNA expression of the FBXW7 beta-form was found in all the human glioma cell lines analyzed; enhanced expressions of CCNE1, MYC, and AURKA were observed in these cells. Our present results imply that FBXW7 plays a pivotal role in many tissues by controlling the amount of cell cycle promoter proteins and that dysfunction of this protein is one of the essential steps in carcinogenesis in multiple organs. PMID- 17274949 TI - Anti-inflammatory effects of 7-methoxycryptopleurine and structure-activity relations of phenanthroindolizidines and phenanthroquinolizidines. AB - A cryptopleurine analogue, 7-methoxycryptopleurine, a phenanthroquinolizidine, was first found to exert potent anti-inflammatory activity in vitro and in vivo as well as have remarkable cytotoxic activity against cancer cells. The non planar structure between the two major moieties, phenanthrene and indolizidine/quinolizidine, played a crucial role in the activity of phenanthroindolizidines or phenanthroquinolizidines in terms of cytotoxic effects on cancer cells and anti-inflammatory activity. We also showed that increase in planarity and rigidity of the indolizidine/quinolizidine moiety and change of the amine group into an amide by introducing a keto group to phenanthroindolizidines or phenanthroquinolizidines at the equivalent position 9 of tylophorine significantly reduced their activities. Moreover, in general, phenanthroquinolizidines are more potent than their respective phenanthroindolizines. PMID- 17274950 TI - Circadian expression of clock genes in human peripheral leukocytes. AB - In mammals, behavioral and physiological processes display 24-h rhythms that are regulated by a circadian system. In the present study, we investigated the possibility that the expression of clock genes in peripheral leukocytes can be used to assess the circadian clock system. We found that Per1 and Per2 exhibit circadian oscillations in mRNA expression in mouse peripheral leukocytes. Furthermore, the rhythms of Per1 and Per2 mRNA expression in peripheral leukocytes are severely blunted in homozygous Cry1/2 double-deficient mice that are known to have an abolished biological clock. We have examined the circadian expression of clock genes in human leukocytes and found that Per1 mRNA exhibits a robust circadian expression while Per2 and Bmal1 mRNA showed weak rhythm. These observations suggest that monitoring Per1 mRNA expression in human leukocytes may be useful for investigating the function of the circadian system in physiological and pathophysiological states. PMID- 17274951 TI - Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure. AB - Success in islet-transplantation-based therapies for type I diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Embryonic stem cells (ESCs) have been successfully induced into insulin producing islet-like structure in several studies. However, the source of the ESCs has presented ethical and technical concerns. Here, we isolated a population of stem cells from human cord blood (UCB), which expressed embryo stage specific maker, SSEA-4, and the multi potential stem cell marker, Oct4. Subsequently, we successfully induced them into insulin-producing islet-like structures, which co-express insulin and C-peptide. These findings might have a significant potential to advance human UCB derived stem-cell-based therapeutics for diabetes. PMID- 17274952 TI - Insulin induces a transcriptional activation of epiregulin, HB-EGF and amphiregulin, by a PI3K-dependent mechanism: identification of a specific insulin responsive promoter element. AB - Previously we have shown that insulin-stimulation of RT4 bladder cancer cells leads to increased proliferation, which require HER1 activation, and is accompanied by increased mRNA expression of the EGF-ligands heparin-binding EGF like growth factor (HB-EGF), amphiregulin (AR), and epiregulin (EPI) [D. Ornskov, E. Nexo, B.S. Sorensen, Insulin-induced proliferation of bladder cancer cells is mediated through activation of the epidermal growth factor system, FEBS J. 273 (2006) 5479-5489]. In the present paper, we have investigated the molecular mechanism leading to this insulin-induced expression. We monitored the decay of mRNA after inhibiting transcription with Actinomycin D and demonstrated that the insulin-mediated increase was not caused by enhanced mRNA stability. In untreated cells, HB-EGF mRNA was the least stable, whereas AR and EPI mRNA decayed with slower kinetics. However, promoter analysis of HB-EGF and EPI demonstrated that insulin stimulated transcription. Studies on the EPI promoter identified the insulin-responsive element to be located in the region -564 to -365bp. This region contains potential binding sites for the transcription factors SP1, AP1, and NF-kappaB. Interestingly, all three transcription factors can be activated by PI3K. We demonstrate that the insulin-induced expression of HB-EGF, AR, and EPI mRNA is completely prevented by the specific PI3K inhibitor Wortmannin, suggesting an involvement of the PI3K. PMID- 17274953 TI - Methylation of the C-terminal leucine residue of the PP2A catalytic subunit is unnecessary for the catalytic activity and the binding of regulatory subunit (PR55/B). AB - Protein phosphatase 2A (PP2A) is composed of structural (A), catalytic (C), and regulatory (B) subunits. The catalytic subunit (PP2A(C)) undergoes reversible carboxyl-methylation and -demethylation at its C-terminal leucine residue (Leu309), catalyzed by PP2A-methyltransferase (PMT) and PP2A methylesterase (PME 1), respectively. In this study, we observed that the activity of PP2A was largely unaffected by the addition of PME-1, and that the regulatory subunit (PR55/B) could bind demethylated PP2A(D). Furthermore, to study the precise effect of Leu309 demethylation on PP2A activity, we generated two His(8)-tagged mutant versions of PP2A(C) containing an alanine residue in place of Leu309, and a deletion of Leu309. Both recombinant mutants exhibited phosphatase activity. In addition, we demonstrated that both mutants could constitute a holoenzyme with the regulatory A and B subunits. Our collective results indicate that methylation of Leu309 of PP2A(C) is unnecessary for the PP2A activity and the binding of PR55/B. PMID- 17274955 TI - The negative transcription factor E4BP4 is associated with circadian clock protein PERIOD2. AB - The bZIP transcription factor E4BP4, is a mammalian homologue of vrille that functions as a key negative component of the circadian clock. We have shown that the E4BP4-binding site (B-site) is required in addition to a non-canonical E-box (E2 enhancer) for robust circadian Period2 (Per2) expression in the cell autonomous clock. While the E2 enhancer and the B-site are closely situated, correlations between each component bound to the E2 enhancer and the B-site remain obscure. Here, we show that E4BP4 interacts with PER2, which represses transcriptional activity via the E-box enhancer. Interaction with PER2 required the carboxyl-terminal region that contains the repression domain of E4BP4. We also found that E4BP4 interacts with CRYPTOCHROME2 (CRY2), a key negative regulator in the mammalian circadian clock. These results suggest that E4BP4 is a component of the negative regulator complex of mammalian circadian clocks. PMID- 17274954 TI - Linking PCNA-dependent replication and ATR by human Claspin. AB - Recent studies in Xenopus have identified a new checkpoint protein called Claspin that is believed to transduce the checkpoint DNA damage signals to Chk1 kinase. Here we show that the human Claspin homolog is a chromatin bound protein either in the absence or in the presence of damaged DNA, independent of its association with ATR. Furthermore, we show that human Claspin is found in complex with PCNA, an essential component of the DNA replication machinery, and is released upon DNA replication arrest. Interfering with PCNA function by overexpression of p21 mutant, impaired in its interaction with Cdks but not with PCNA, leads to ATR dependent Chk1 activation. These findings suggest that the dissociation of Claspin-PCNA could be part of the signal leading to Chk1 activation. PMID- 17274956 TI - In vitro characterization of the effects of endomorphin 1 and 2, endogenous ligands for mu-opioid receptors, on mouse colonic motility. AB - The effects of endomorphin 1 (EM1) and 2 (EM2) in colonic motility remain unknown. We investigated the effects and mechanisms of these endomorphins (EMs) on the colonic motility in vitro by applying various neural blocking agents and various opioid receptor antagonists. EMs (10(-9) to 10(-6)M) displayed significant stimulatory effects on the basal tonus or spontaneous activity of mouse colon but not of stomach and small intestine. It is noteworthy that the contractile actions of EMs varied slightly among different regions of colonic longitudinal muscle layers, whereas the contractile responses induced by EMs were significantly different among different regions of circular muscle layers. EMs induced longitudinal or circular muscle contractions were not significantly affected by atropine, N(G)-nitro-l-arginine methyl ester, phentolamine, propranolol and methysergide. Tetrodotoxin, indomethacin and naloxone completely abolished the EMs-induced colonic contractions. Surprisingly, EMs (10(-7)M) induced longitudinal muscle contractions were significantly attenuated by nor binaltorphimine (3x10(-6)M). By contrast, pretreatment with naltrindole (10(-6)M) did not significantly affect EMs-induced longitudinal or circular muscle contractions. Interestingly, the circular muscle contractions in response to EM2 (10(-7)M) were not fully blocked by beta-funaltrexamine (6x10(-6)M). Naloxonazine (10(-6)M) almost fully antagonized the EMs-induced longitudinal or circular muscle contractions, and these effects could be only partially reversed by extensive washing. All the results indicated that the mechanisms and sites of actions of EMs were region-specific. Furthermore, these findings showed that the activation of multiple subtypes of opioid receptors, possibly including mu(1) (naloxonazine-sensitive), mu(2) and even other forms of muORs (beta-FNA insensitive), was required for EMs-induced mouse colonic motility. PMID- 17274958 TI - The dual-peak light response of ganglion cells in chicken retina. AB - In the present study, a particular temporal pattern of the ganglion cells' light response specified as "dual-peak" was observed. In the chicken retina (N=15), about 37.5% (174 out of 464) of the ganglion cells showed such special temporal property in response to the onset of light flash. These neurons responded to light stimulus with two successive components: a transient increase of firing rate which lasted for less than 100 ms, and another prolonged light response appeared in about 100 ms after the first transient response. Moreover, our data demonstrated a temporal adaptation process in the later phase of firing activities when repeated flashes were applied. Meanwhile, the earlier phase had a more stable latency in response to the stimulus. Application of picrotoxin could evoke the dual-peak responses in transient ganglion cells. These results suggest that the origination of the two response components might be distinct and the later one is likely related to GABAergic pathways. PMID- 17274957 TI - Capsaicin causes protein synthesis inhibition and microtubule disassembly through TRPV1 activities both on the plasma membrane and intracellular membranes. AB - TRPV1 is a non-selective cationic channel that is activated by capsaicin, acidic pH and thermal stimuli. Sustained TRPV1 channel activation causes severe cytotoxicity that leads to cell death. In this study, we investigated the mechanisms of capsaicin-induced cytotoxicity in HEK293 cells stably expressing TRPV1 with a focus on protein synthesis regulation and cytoskeleton reorganization. Capsaicin inhibited protein synthesis in TRPV1-expressing HEK cells with an IC(50) of 15.6nM and depolymerized microtubules within 10min after exposure. These effects were completely blocked by pretreatment of cells with the TRPV1 antagonist A-425619, both in the presence and absence of extracellular calcium. Protein synthesis inhibition induced by capsaicin was not a result of eIF2alpha hyperphosphorylation, but rather closely correlated with cytosolic calcium elevation caused by calcium flux through cell surface and intracellular TRPV1, and/or ER calcium depletion through intracellular TRPV1. Microtubule dependent cell process shrinkage may serve as a mechanism for rapid alteration of the neurotransmission network upon TRPV1 activation. Taken together, the present studies demonstrate that intracellular pool of TRPV1 plays an important role in regulating cell morphology and viability upon receptor activation. PMID- 17274959 TI - Role of astrocytes in grey matter during stroke: a modelling approach. AB - The astrocytic response to stroke is extremely complex and incompletely understood. On the one hand, astrocytes are known to be neuroprotective when extracellular glutamate or potassium is slightly increased. But, on the other hand, they are considered to contribute to the extracellular glutamate increase during severe ischaemia. A mathematical model is used to reproduce the dynamics of the membrane potentials, intracellular and extracellular concentrations and volumes of neurons and astrocytes during ischaemia in order to study the role of astrocytes in grey matter during the first hour of a stroke. Under conditions of mild ischaemia, astrocytes are observed to take up glutamate via the glutamate transporter, and potassium via the Na/K/Cl cotransporter, which limits glutamate and potassium increase in the extracellular space. On the contrary, under conditions of severe ischaemia, astrocytes appear to be unable to maintain potassium homeostasis. Moreover, they are shown to contribute to the excitotoxicity process by expelling glutamate out of the cells via the reversed glutamate transporter. A detailed understanding of astrocytic function and influence on neuron survival during stroke is necessary to improve the neuroprotective strategies for stroke patients. PMID- 17274960 TI - Sex-related hemispheric lateralization of electrical potentials evoked by arousing negative stimuli. AB - Recent studies suggest that both sex and cerebral hemisphere influence brain mechanisms associated with emotional memory. Here we used evoked potentials to examine the influence of sex and hemisphere on brain responses to emotional stimuli. Given that the P300 component of the event-related brain potential (ERP) is considered a cognitive neuroelectric phenomenon, we compared left and right hemisphere P300 responses to brief (2 s) presentations of emotionally arousing pictures in men and women. P300 waves were recorded from sites overlying left (F3 and P3) and right (F4 and P4) hemisphere frontal and parietal locations in response to a series of standardized pictures rated as emotionally negative, positive, or neutral. Negative pictures elicited more robust P300 effects, as indexed by both amplitude and latency measures, in the left hemisphere in women than in men, yet elicited a stronger P300 component in the right hemisphere in men than in women. The variables of sex and hemisphere interacted significantly to influence the strength of the P300 component to the negative slides. Negative slides were also best recalled at a long-term, incidental memory test, a fact potentially related to the differential P300 waves at encoding. These data further support the view that both sex and cerebral hemisphere represent relevant, interacting influences on neural correlates of emotion, and of emotionally influenced memory. PMID- 17274961 TI - Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. AB - This paper studied the effects of crocin, a pharmacologically active component of Crocus sativus L., on ischemia/reperfusion (I/R) injury in mice cerebral microvessels. Transient global cerebral ischemia (20 min), followed by 24 h of reperfusion, significantly promoted the generation of nitric oxide (NO) and malondialdehyde (MDA) in cortical microvascular homogenates, as well as markedly reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and promoted the activity of nitric oxide synthase (NOs). Reperfusion for 24 h led to serous edema with substantial microvilli loss, vacuolation, membrane damage and mitochondrial injuries in cortical microvascular endothelial cells (CMEC). Furthermore, enhanced phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and decreased expression of matrix metalloproteinase-9 (MMP-9) were detected in cortical microvessels after I (20 min)/R (24 h). Reperfusion for 24 h also induced membrane (functional) G protein coupled receptor kinase 2 (GRK2) expression, while it reduced cytosol GRK2 expression. Pretreatment with crocin markedly inhibited oxidizing reactions and modulated the ultrastructure of CMEC in mice with 20 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 h of reperfusion in vivo. Furthermore, crocin inhibited GRK2 translocation from the cytosol to the membrane and reduced ERK1/2 phosphorylation and MMP-9 expression in cortical microvessels. We propose that crocin protects the brain against excessive oxidative stress and constitutes a potential therapeutic candidate in transient global cerebral ischemia. PMID- 17274962 TI - Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity. AB - The formation of Abeta and its subsequent deposition in senile plaques are considered to be initial events that lead to a cascade of pathological changes in AD. Mediators of Abeta-induced oxidative stress are known to cause oxidative damage to macromolecules. However, the molecular mechanisms by which Abeta induced oxidative stress leads to neuronal cell death are not fully understood. Here we show that Abeta-induced oxidative stress activates the pro-death gene BNIP3. Abeta treatment results in mitochondrial dysfunction, accumulation of reactive oxygen species, and subsequent expression of BNIP3 in rat primary cortical neurons. Pretreatment with antioxidants abolished Abeta-induced BNIP3 expression and attenuated cell death, demonstrating the role of oxidative stress in BNIP3 induction. Abeta-induced BNIP3 expression may be mediated by hypoxia inducible factor-1 (HIF-1) because Abeta-treatment induced accumulation and nuclear translocation of HIF-1 and knock-down of HIF-1 by RNAi inhibited BNIP3 expression. Finally, knockdown of BNIP3 reduced Abeta-induced neuronal death. Together, these results suggest a potential pathological role of BNIP3 in the etiology of AD. PMID- 17274963 TI - Effects of early methylphenidate exposure on morphine- and sucrose-reinforced behaviors in adult rats: relationship to dopamine D2 receptors. AB - Methylphenidate is commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD) in school-aged children, and there is an increasing trend to prescribe methylphenidate to younger preschool-aged children. While the efficacy of methylphenidate is not in question, there is evidence that early methylphenidate treatment may have long-term effects on later drug responsiveness. The goal of this study was to determine whether early exposure to methylphenidate would alter morphine-induced conditioned place preference (CPP) and sucrose-reinforced lever-pressing in young adult rats. We also assessed whether early methylphenidate exposure would impact dopamine D(2) binding sites. Sprague-Dawley rats were treated with methylphenidate (0, 2, or 5 mg/kg) once a day from PD 11-PD 20. On PD 60, morphine-induced CPP or sucrose-reinforced lever pressing was assessed. A 10-day CPP procedure was used, which included 1 preconditioning day, 8 conditioning days, and 1 test day. After CPP testing, D(2) receptor binding was determined in striatal and accumbal tissue samples. In the sucrose experiment, rats were trained to lever-press on a progressive ratio schedule for one sucrose pellet. Results showed that early exposure to methylphenidate (5 mg/kg) increased the magnitude of morphine-induced CPP. Exposure to methylphenidate did not alter the number of D(2) binding sites, however, there were positive correlations between the number of D(2) binding sites and the strength of the CPP. In the sucrose-reinforced lever-press experiment, rats exposed to methylphenidate (2 and 5 mg/kg) had higher break points than saline controls. These results suggest that early exposure to methylphenidate alters reward system functioning, thereby making these systems more sensitive to appetitive stimuli. PMID- 17274964 TI - Moclobemide attenuates anoxia and glutamate-induced neuronal damage in vitro independently of interaction with glutamate receptor subtypes. AB - Recent data suggested the existence of a bidirectional relation between depression and neurodegenerative diseases resulting from cerebral ischemia injury. Glutamate, a major excitatory neurotransmitter, has long been recognised to play a key role in the pathophysiology of anoxia or ischemia, due to its excessive accumulation in the extracellular space and the subsequent activation of its receptors. A characteristic response to glutamate is the increase in cytosolic Na(+) and Ca(2+) levels which is due mainly to influx from the extracellular space, with a consequent cell swelling and oxidative metabolism dysfunction. The present study examined the in vitro effects of the antidepressant and type-A monoamine oxidase inhibitor, moclobemide, in neuronal astroglial cultures from rat cerebral cortex exposed to anoxia (for 5 and 7 h) or to glutamate (2 mM for 6 h), two in vitro models of brain ischemia. In addition, the affinity of moclobemide for the different glutamate receptor subtypes and an interaction with the cell influx of Na(+) and of Ca(2+) enhanced by veratridine and K(+) excess, respectively, were evaluated. Moclobemide (10-100 microM) included in the culture medium during anoxia or with glutamate significantly increased in a concentration-dependent manner the amount of surviving neurons compared to controls. Moclobemide displayed no binding affinity for the different glutamate receptor subtypes (IC(50)>100 microM) and did not block up to 300 microM the entry of Na(+) and of Ca(2+) activated by veratridine and K(+), respectively. These results suggest that the neuroprotective properties of moclobemide imply neither the glutamate neurotransmission nor the Na(+) and Ca(2+) channels. PMID- 17274965 TI - Intranasal trigeminal function in subjects with and without an intact sense of smell. AB - The intranasal trigeminal system is involved in the perception of odors. To investigate the cerebral processing of sensory information from the trigeminal nerve in detail we studied subjects with and without olfactory function using functional magnetic resonance imaging. A normosmic group (n=12) was compared with a group of anosmic subjects (n=11). For trigeminal stimulation gaseous CO(2) was used. Following right-sided stimulation with CO(2) controls exhibited a stronger right-sided cerebral activation than anosmic subjects. Stronger activation was found in controls compared to anosmic subjects for the right prefrontal cortex, the right somatosensory cortex (SI), and the left parietal insula. In contrast, relatively higher activation was found in anosmic subjects for the left supplementary motor area in the frontal lobe, the right superior and middle temporal lobe, the left parahippocampal gyrus in the limbic lobe, and the sub lobar region of the left putamen and right insula which was mostly due to a decreased BOLD signal of controls in these areas. Additional conjunction analysis revealed that activated areas common to the two groups were the cerebellum and the right premotor frontal cortex. These data suggest that the processing of the trigeminally mediated information is different in the presence or absence of an intact sense of smell, pointing towards the intimate connection between the two chemosensory systems. PMID- 17274966 TI - Post-tetanic potentiation of GABAergic IPSCs in cultured hippocampal neurons is exclusively time-dependent. AB - We have previously shown that post-tetanic potentiation (PTP) of GABAergic IPSCs in cultured hippocampal neurons involves activation of L-type Ca(2+) channels. Although there is little Ca(2+) entry by this route, it is possible that L-type Ca(2+) channels mediate an increase in probability of release (Pr) by a mechanism that remains dormant in the absence of stimulation. We have tested this hypothesis in the present study using dual whole-cell patch clamp recordings. IPSCs were evoked by low-frequency stimulation (LFS; 0.2 Hz) of presynaptic GABAergic neurons. Run-down was corrected by linear regression. Following tetanic stimulation (80 pulses at 40 Hz), the presence of PTP was probed by resuming LFS after various post-tetanic intervals (PTI). To control for possible effects associated with LFS, the train and PTI were replaced by corresponding pauses. Following pauses >or=16 s, the first IPSC was significantly increased by 20-25% (P<0.01, paired t-test). These post-pause responses were subtracted from IPSCs following tetanic stimulation. Following correction, PTP was greatest ( approximately 50%) after the shortest PTI (4 s) and IPSC amplitudes declined back to the baseline value over 1-2 min. With a PTI of 16 s, the first IPSC was potentiated to the same level as that to which PTP with a PTI of 4 s had decayed with continued LFS. There was no significant PTP with PTIs of 64 and 128 s. Since PTP decays entirely in the absence of stimulation, it is concluded that the process(es) mediating the increase in vesicular Pr appear to be time-dependent, but not use-dependent. PMID- 17274967 TI - Vasorelaxant and antioxidant activity of the isoflavone metabolite equol in carotid and cerebral arteries. AB - BACKGROUND AND PURPOSE: Equol is the main active intestinal metabolite of the isoflavone daidzein and is postulated to be responsible for the cardiovascular benefits of soy. Cerebral vascular effects of equol are unknown. We compared the vasorelaxant and antioxidant effects of equol and daidzein in carotid and basilar artery of normal and hypertensive rats. EXPERIMENTAL APPROACH: Relaxant responses to equol and daidzein were measured in the isolated carotid artery and in the basilar artery in vivo. Effects of nitric oxide synthase (NOS) inhibition, high extracellular K(+), endothelial removal and gender on responses to equol were investigated in carotid arteries. Antioxidant activity was assessed as the reduction of NADPH-induced superoxide levels. Hypertension was induced using angiotensin II (0.7 mg/kg per day for 14 days). KEY RESULTS: In normotensive rats, equol displayed vasorelaxant activity similar to daidzein. The relaxant effect of equol was independent of an intact endothelium, NOS activity, K(+) channels and gender. In the basilar artery, where superoxide levels are higher, equol exerted weak antioxidant effects, whereas effects of daidzein were insignificant. During hypertension, equol-induced vasorelaxation was preserved, whereas relaxant responses to daidzein were impaired. CONCLUSIONS AND IMPLICATIONS: Equol possesses substantial vasodilator and weak antioxidant activity in cerebral arteries, with similar activity to daidzein, whereas in hypertension the vasorelaxant response to equol, but not daidzein, is preserved. However, daidzein possesses comparable direct vascular effects with equol, without the need for intestinal conversion to equol. Nevertheless, equol may represent a more useful therapeutic agent during cerebral vascular disease. PMID- 17274968 TI - The myocardial no-reflow phenomenon: role of deltaPKC. PMID- 17274969 TI - Oxidative stress injury during cardiac surgery: how important is it? PMID- 17274970 TI - Copper modifies liver microsomal UDP-glucuronyltransferase activity through different and opposite mechanisms. AB - Treatment of hepatic microsomes with Fe(3+)/ascorbate activates UDP glucuronyltransferase (UGT), a phenomenon totally prevented and reversed by reducing agents. At microM concentrations, iron and copper ions catalyze the formation of ROS through Fenton and/or Haber-Weiss reactions. Unlike iron ions, indiscriminate binding of copper ions to thiol groups of proteins different from the specialized copper-binding proteins may occur. Thus, we hypothesize that incubation of hepatic microsomes with the Cu(2+)/ascorbate system will lead to both UGT oxidative activation and Cu(2+)-binding induced inhibition, simultaneously. We studied the effects of Cu(2+) alone and in the presence of ascorbate on rat liver microsomal UGT activity. Our results show that the effects of both copper alone and in the presence of ascorbate were copper ion concentration- and incubation time-dependent. At very low Cu(2+) (25nM), this ion did not modify UGT activity. In the presence of ascorbate, however, UGT activity was increased. At higher copper concentrations (10 and 50microM), this ion led to UGT activity inhibition. In the presence of ascorbate, 10microM Cu(2+) activated UGT at short incubation periods but inhibited this enzyme at longer incubation times; 50microM Cu(2+) only inhibited UGT activity. Thiol reducing agent 2,4 dithiothreitol prevented and reversed UGT activation while EDTA prevented both, UGT activation and inhibition. Our results are consistent with a model in which Cu(2+)-induced oxidation of UGT leads to the activation of the enzyme, while Cu(2+)-binding leads to its inhibition. We discuss physiological and pathological implications of these findings. PMID- 17274971 TI - Inhibition or activation of Pseudomonas species lipase by 1,2-ethylene-di-N alkylcarbamates in detergents. AB - 1,2-Ethylene-di-N-n-propylcarbamate (1) is characterized as an essential activator of Pseudomonas species lipase while 1,2-ethylene-di-N-n-butyl-, t-butyl , n-heptyl-, and n-octyl-carbamates (2-5) are characterized as the pseudo substrate inhibitors of the enzyme in the presence of the detergent taurocholate or triton X-100. The inhibition and activation reactions are more sensitive in taurocholate than in triton X-100. From CD studies, the enzyme changes conformations in the presence of the detergent and further alters conformations by addition of the carbamate activator or inhibitor into the enzyme-detergent adduct. Therefore, this study suggests that the conformational change of lipase during interfacial activation is a continuous process to expose the active site of the enzyme to substrate. From 600 MHz (1)H NMR studies, the conformations of the alpha- and beta-methylene moieties of the activator 1,2-ethylene-di-N-n propylcarbamate in the presence of substrate change after adding taurocholate into the mixture, and the conformations of the beta-methylene moieties of the inhibitor 1,2-ethylene-di-N-n-butylcarbamate in the presence of substrate alter after adding taurocholate into the mixture. PMID- 17274972 TI - Defects in ordered aggregates of cardiolipin visualized by atomic force microscopy. AB - The formation and the nature of defects in ordered aggregates of cardiolipin (tetra acyl diphosphatidylglycerol) supported on solid substrates have been investigated by atomic force microscopy (AFM). The experiments were performed on two model systems, i.e. three-dimensional liquid crystals dispersed in water and partially de-hydrated on a hydrophilic surface, and two-dimensional films of molecules self-assembled onto an isotropic hydrophobic surface. Defects were induced both by varying the preparation temperature and by treatment with specific chemicals known to modify the order parameters in natural and artificial membranes, specifically: 2,4-dinitro-phenol (DNP) and pentachloro-phenol (PCP). The effect of lipid oxidation on the nanocrystalline order was also investigated. The images obtained by AFM allow to characterize the type of defects and their local density at nanoscale level. They also provide additional information to differentiate the specific role of acyl chains and polar heads in the process of lipid self-organization. PMID- 17274973 TI - Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia. AB - Nitric oxide and prostacyclin are endogenous endothelium-derived vasodilators, but little information is available on their release during hypothermia. This study was carried out to test the hypothesis that endothelium may modulate vascular reactivity to decreased temperature changes. Segments of contracted (prostaglandin F(2alpha), 2x10(-6)M) canine coronary, femoral, and renal arteries, with and without endothelium, were in vitro ("organ chambers") exposed to progressive hypothermia (from 37 to 10 degrees C) in graded steps. The study is limited to physiological measurements of vascular tone, in the presence or absence of PGI(2) and/or NOS inhibitors, which show correlation with the relaxation. Hypothermia induced vasodilatation of vessels with intact endothelium, which became endothelium-independent below 20 degrees C. This vasodilatation began at 35 degrees C and, in the presence of indomethacin (2x10( 6)M), at 30 degrees C. Endothelium-dependent vasodilatation to hypothermia was blocked by L-NMMA or L-NOARG (10(-5)M), two competitive inhibitors of nitric oxide synthase (n=5 each, P<0.05). Oxyhemoglobin (2x10(-6)M) also inhibited vasodilatation induced by hypothermia (n=6, P<0.05). Pretreatment with either atropine or pirenzepine (10(-6)M) inhibited hypothermia-mediated vasodilatation (n=5 each, P<0.05). The present in vitro study concluded that the endothelium is sensitive to temperature variations and indicated that PGI(2) and NO-dependent pathways may be involved endothelium-dependent relaxation to hypothermia. The endothelium-dependent vasodilatation to hypothermia, in systemic and coronary arteries, is mediated by the M1 muscarinic receptor. PMID- 17274975 TI - Time-lapse and retrospective analysis of DNA methylation in mouse preimplantation embryos by live cell imaging. AB - Genome-wide change of DNA methylation in preimplantation embryos is known to be important for the nuclear reprogramming process. A synthetic RNA encoding enhanced green fluorescence protein fused to the methyl-CpG-binding domain and nuclear localization signal of human MBD1 was microinjected into metaphase II arrested or fertilized oocytes, and the localization of methylated DNA was monitored by live cell imaging. Both the central part of decondensing sperm nucleus and the rim region of the nucleolus in the male pronucleus were highly DNA-methylated during pronuclear formation. The methylated paternal genome undergoing active DNA demethylation in the enlarging pronucleus was dispersed, assembled, and then migrated to the nucleolar rim. The female pronucleus contained methylated DNA predominantly in the nucleoplasm. When the localization of methylated DNA in preimplantation embryos was examined, a configurational change of methylated chromatin dramatically occurred during the transition of 2 cell to 4-cell embryos. Moreover, retrospective analysis demonstrated that a noticeable number of the oocytes reconstructed by round spermatid injection (ROSI) possess small, bright dots of methylated chromatin in the nucleoplasm of male pronucleus. These ROSI oocytes showed a significantly low rate of 2-cell formation, thus suggesting that the poor embryonic development of the ROSI oocytes may result from the abnormal localization of methylated chromatin. PMID- 17274974 TI - FOG-2 attenuates endothelial-to-mesenchymal transformation in the endocardial cushions of the developing heart. AB - Development of the heart valves is a complex process that relies on the successful remodeling of endocardial cushions. This process is dependent on a number of transcriptional regulators, including GATA4 and its interacting partner FOG-2. We have previously shown that the endocardial cushions in FOG-2 deficient mice are hyperplastic and fail to remodel appropriately, suggesting a defect late in endocardial cushion development. To elucidate this defect, we examined the later steps in endocardial cushion development including mesenchymal cell proliferation, differentiation, and apoptosis. We also measured myocardialization and endothelial-to-mesenchymal transformation (EMT) using previously described in vitro assays. We found no difference in the ability of the endocardial cushions to undergo myocardialization or in the rates of mesenchymal cell proliferation, differentiation, or apoptosis in the FOG-2 deficient cushions when compared to wild-type controls. However, using a collagen gel invasion assay, we found a 78% increase in outflow tract cushion EMT and a 35% increase in atrioventricular cushion EMT in the FOG-2 deficient mice when compared with wild-type mice. Taken together with GATA4's known role in promoting EMT, these results suggest that FOG 2 functions in cardiac valve formation as an attenuator of EMT by repressing GATA4 activity within the developing endocardial cushions. PMID- 17274976 TI - Completing the set of h/E(spl) cyclic genes in zebrafish: her12 and her15 reveal novel modes of expression and contribute to the segmentation clock. AB - Somitogenesis is the key developmental process that lays down the framework for a metameric body in vertebrates. Somites are generated from the un-segmented presomitic mesoderm (PSM) by a pre-patterning process driven by a molecular oscillator termed the segmentation clock. The Delta-Notch intercellular signaling pathway and genes belonging to the hairy (h) and Enhancer of split (E(spl)) related (h/E(spl)) family of transcriptional repressors are conserved components of this oscillator. A subset of these genes, called cyclic genes, is characterized by oscillating mRNA expression that sweeps anteriorly like a wave through the embryonic PSM. Periodic transcriptional repression by H/E(spl) proteins is thought to provide a critical part of a negative feedback loop in the oscillatory process, but it is an open question how many cyclic h/E(spl) genes are involved in the somitogenesis clock in any species, and what distinct roles they might play. From a genome-wide search for h/E(spl) genes in the zebrafish, we previously estimated a total of five cyclic members. Here we report that one of these, the mHes5 homologue her15 actually exists as a very recently duplicated gene pair. We investigate the expression of this gene pair and analyse its regulation and activity in comparison to the paralogous her12 gene, and the other cyclic h/E(spl) genes in the zebrafish. The her15 gene pair and her12 display novel and distinct expression features, including a caudally restricted oscillatory domain and dynamic stripes of expression in the rostral PSM that occur at the future segmental borders. her15 expression stripes demarcate a unique two-segment interval in the rostral PSM. Mutant, morpholino, and inhibitor studies show that her12 and her15 expression in the PSM is regulated by Delta Notch signaling in a complex manner, and is dependent on her7, but not her1 function. Morpholino-mediated her12 knockdown disrupts cyclic gene expression, indicating that it is a non-redundant core component of the segmentation clock. Over-expression of her12, her15 or her7 disrupts cyclic gene expression and somite border formation, and structure function analysis of Her7 indicates that DNA binding, but not Groucho-recruitment seems to be important in this process. Thus, the zebrafish has five functional cyclic h/E(spl) genes, which are expressed in a distinct spatial configuration. We propose that this creates a segmentation oscillator that varies in biochemical composition depending on position in the PSM. PMID- 17274977 TI - Diffusion analysis of glucocorticoid receptor and antagonist effect in living cell nucleus. AB - The diffusion properties of hGRalpha in living cells have been analyzed. The hGRalpha translocalized from the cytosol to the nucleus after addition of Dex just as RU486; however, the Brownian motions of the proteins in nucleus were different. In order to analysis microenvironment of the nucleus of living cell, four different tandem EGFPs were constructed. Diffusion of tandem EGFP was dependent on the length of the protein as a rod-like molecule in solution. We found two kinds of mobility, fast diffusional mobility as a major component and much slower diffusional mobility as a major component in living cells nucleoplasm. On the bases of this analysis, we compared the diffusion property of hGRalpha in the nucleus at the presence of Dex or RU486 by distribution of diffusion constants. Our result may suggest that EGFP-hGRalpha is activated by RU486 and kept the stage of binding cofactor, GRE and final complex. Finally this means that dimerization is not required for association with GRE, although it is required for stabilization of a complex of EGFP-hGRalpha. PMID- 17274978 TI - Inhibition of activin receptor-like kinase 5 attenuates bleomycin-induced pulmonary fibrosis. AB - Activin receptor-like kinase 5 (ALK5) is a type I receptor of transforming growth factor (TGF)-beta. ALK5 inhibition has been reported to attenuate the tissue fibrosis including pulmonary fibrosis, renal fibrosis and liver fibrosis. To elucidate the inhibitory mechanism of ALK5 inhibitor on pulmonary fibrosis in vivo, we performed the histopathological assessment, gene expression analysis of extracellular matrix (ECM) genes and immunohistochemistry including receptor activated Smads (R-Smads; Smad2/3), CTGF, myofibroblast marker (alpha-smooth muscle actin; aSMA) and type I collagen deposition in the lung using Bleomycin (BLM)-induced pulmonary fibrosis model. ALK5 inhibitor, SB-525334 (10 mg/kg or 30 mg/kg) was orally administered at twice a day. Lungs were isolated 5, 7, 9 and 14 days after BLM treatment. BLM treatment led to significant pulmonary fibrotic changes accompanied by significant upregulation of ECM mRNA expressions, Smad2/3 nuclear translocation, CTGF expression, myofibroblast proliferation and type I collagen deposition. SB-525334 treatment attenuated the histopathological alterations in the lung, and significantly decreased the type I and III procollagen and fibronectin mRNA expression. Immunohistochemistry revealed that SB-525334 treatment showed significant attenuation in Smad2/3 nuclear translocation, decrease in CTGF-expressing cells, myofibroblast proliferation and type I collagen deposition. These results suggest that ALK5 inhibition attenuates R-Smads activation thereby attenuates pulmonary fibrosis. PMID- 17274980 TI - Coronin 3 involvement in F-actin-dependent processes at the cell cortex. AB - The actin interaction of coronin 3 has been mainly documented by in vitro experiments. Here, we discuss coronin 3 properties in the light of new structural information and focus on assays that reflect in vivo roles of coronin 3 and its impact on F-actin-associated functions. Using GFP-tagged coronin 3 fusion proteins and RNAi silencing we show that coronin 3 has roles in wound healing, protrusion formation, cell proliferation, cytokinesis, endocytosis, axonal growth, and secretion. During formation of cell protrusions actin accumulation precedes the focal enrichment of coronin 3 suggesting a role for coronin 3 in events that follow the initial F-actin assembly. Moreover, we show that coronin 3 similar to other coronins interacts with the Arp2/3-complex and cofilin indicating that this family in general is involved in regulating Arp2/3-mediated events. PMID- 17274981 TI - Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart. AB - During the past several years increasing evidence indicating that the proliferation capacity of mammalian cells is highly radiosensitive, regardless of the species and the tissue of origin of the cells, has accumulated. It has also been shown that normal bone marrow cells of mice have a similar radiosensitivity to other mammalian cells so far tested. In this study, we investigated the genetic effects of ionizing radiation (2.5-15 Gy) on normal human mesenchymal stem cells and their telomerised counterpart hMSC-telo1. We evaluated overall genomic integrity, DNA damage/repair by applying a fluorescence-detected alkaline DNA unwinding assay together with Western blot analyses for phosphorylated H2AX and Q-FISH was applied for investigation of telomeric damage. Our results indicate that hMSC and TERT-immortalized hMSCs can cope with relatively high doses of gamma-rays and that overall DNA repair is similar in the two cell lines. The telomeres were extensively destroyed after irradiation in both cell types suggesting that telomere caps are especially sensitive to radiation. The TERT immortalized hMSCs showed higher stability at telomeric regions than primary hMSCs indicating that cells with long telomeres and high telomerase activity have the advantage of re-establishing the telomeric caps. PMID- 17274979 TI - Regulation of clusterin expression in mammary epithelial cells. AB - Mammary epithelial cells undergo changes in growth, invasion, differentiation, and dedifferentiation throughout much of adult hood, and most strikingly during pregnancy, lactation, and involution. Clusterin is a multifunctional glycoprotein that is involved in the differentiation and morphogenesis of epithelia, and that is important in the regulation of postnatal mammary gland development. However, the mechanisms that regulate clusterin expression are still poorly understood. Here, we show that clusterin is up-regulated twice during mouse mammary gland development, a first time at the end of pregnancy and a second time at the beginning of the involution. These points of clusterin up-regulation coincide with the dramatic phenotypic and functional changes occurring in the mammary gland. Using cell culture conditions that resemble the regulatory microenvironment in vivo, we determined that the factors responsible for the first up-regulation of clusterin levels can include the extracellular matrix component, laminin, and the lactogenic hormones, prolactin and hydrocortisone. On the other hand, the second and most dramatic up-regulation of clusterin can be due to the potent induction by TGF-beta1, and this up-regulation by TGF-beta1 is dependent on beta1 integrin ligand-binding activity. Moreover, the level of expression of beta-casein, a marker of mammary epithelial cell differentiation, was decreased upon treatment of cells with clusterin siRNA. Overall, these findings reveal several novel pathways for the regulation of clusterin expression during mammary gland development, and suggest that clusterin is a morphogenic factor that plays a key role during differentiation. PMID- 17274983 TI - Butyrylcholinesterase activity in the rat forebrain and upper brainstem: postnatal development and adult distribution. AB - Unlike the development of acetylcholinesterase (AChE) activity, the postnatal development of the activity of the related enzyme butyrylcholinesterase (BuChE) in the rodent brain has not been investigated in a comprehensive manner. The purpose of the present study was to fill this gap. Development of histochemically visualized BuChE activity followed four distinct stages. Between birth and five postnatal days (P0-P5) BuChE staining of very low intensity was present in nearly all neurons in the forebrain and upper brainstem. Substantial BuChE activity was present in the endothelial cells of blood vessels and the cuboidal cells lining the ventricles. At P6-P10, BuChE neuronal staining of high to moderate intensity emerged in many areas, including certain thalamic nuclei (e.g. anterior group), a number of brainstem nuclei, and darkly stained neurons in the olfactory tubercle/piriform cortex. At P11-P17, the staining which emerged in earlier stages was darker and had expanded to include more neurons. A scattered population of BuChE-positive neurons of moderate to high intensity emerged in the neocortex and amygdala. Importantly, at P17, the very light staining present in all neurons since birth was no longer visible. At P18-P30, the number and staining intensity of cortical neurons displayed a gradual increase while the staining in certain thalamic nuclei was substantially decreased or completely disappeared (e.g. ventral lateral nucleus). A prominent feature of this stage was the emergence of BuChE activity in many fiber tracts. At P30, the adult pattern of staining was attained. The transient presence of BuChE activity of very low intensity in all neurons and of higher intensity in thalamic neurons supports the implied role for this enzyme in neuronal development. PMID- 17274982 TI - CNTF promotes the survival and differentiation of adult spinal cord-derived oligodendrocyte precursor cells in vitro but fails to promote remyelination in vivo. AB - Delivery of factors capable of promoting oligodendrocyte precursor cell (OPC) survival and differentiation in vivo is an important therapeutic strategy for a variety of pathologies in which demyelination is a component, including multiple sclerosis and spinal cord injury. Ciliary neurotrophic factor (CNTF) is a neuropoietic cytokine that promotes both survival and maturation of a variety of neuronal and glial cell populations, including oligodendrocytes. Present results suggest that, although CNTF has a potent survival and differentiation promoting effect in vitro on OPCs isolated from the adult spinal cord, CNTF administration in vivo is not sufficient to promote oligodendrocyte remyelination in the glial depleted environment of unilateral ethidium bromide (EB) lesions. PMID- 17274984 TI - Trypanosoma cruzi (kinetoplastida Trypanosomatidae): biological heterogeneity in the isolates derived from wild hosts. AB - The course of experimental infection of Swiss mice with 95 sylvatic Trypanosoma cruzi isolates included in TCI or TCII genotype was characterized. The purpose was to verify biological properties and its eventual correspondence with original host species, genotype or zymodeme. The isolates of T. cruzi were 100% infective, 55% resulted in patent parasitemia with 69% (36/52) of mortality. A meaningful biological heterogeneity was observed in both, TCI and TCII isolates. TCII isolates resulted in higher patent parasitemia 64% (38/59), in contrast to the 41% TCI infected Swiss mice (14/34). Parasitemia was not always associated to mortality. Higher biological heterogeneity was observed in T. cruzi II isolates derived from L. rosalia from the Atlantic Coastal Rain forest. TCII isolates derived from marsupials resulted in very similar infection profile in Swiss mice. PMID- 17274985 TI - Ceramide kinase regulates growth and survival of A549 human lung adenocarcinoma cells. AB - Ceramide-1-phosphate (C1P) is emerging as a new addition to the family of bioactive sphingolipid metabolites. At low concentrations, C1P enhanced survival of NIH 3T3 fibroblasts and A549 lung cancer cells, while at high concentrations, it reduced survival and induced apoptosis. Apoptosis correlated with degradation of C1P to pro-apoptotic ceramide. To examine the role of endogenous C1P, expression of ceramide kinase, the enzyme that produces C1P, was downregulated, which reduced cellular proliferation, progression into S phase and enhanced apoptosis induced by serum starvation. Our results suggest that ceramide kinase determines the balance between pro-apoptotic ceramide and anti-apoptotic C1P to regulate cell fate, reminiscent of its function in plants. PMID- 17274986 TI - Bioinformatic tools uncover the C-terminal strand of Rubisco's large subunit as hot-spot for specificity-enhancing mutations. AB - Rubisco assumes the double role of accumulating biomass by fixing carbon dioxide to ribulose-1,5-bisphosphate and binding of molecular oxygen to the same substrate. The specificity factor of this mutually competitive activity, defined as the ratio of carboxylation to oxygenation efficiency, varies considerably for reasons which remain obscure. The explanation and the enhancement of specificity are of high theoretical and practical interest. Despite a wealth of structures and experimental findings, the systematic analysis of available data is still at its beginning. Here, we (a) present an analysis of sequences of the large subunit which reliably finds specificity-enhancing mutations and ranks them according to the probability of success. For mutations near the C-terminus, we (b) show by simulations that the positive influence they have on specificity can be explained by the time-window hypothesis. PMID- 17274987 TI - CD14 is a ligand for the integrin alpha4beta1. AB - Cell adhesion mediated by the integrin alpha4beta1 plays a key role in many biological processes reflecting both the number and functional significance of alpha4beta1 ligands. The lipopolysaccharide (LPS) receptor, CD14, is a GPI-linked cell surface glycoprotein with a wide range of reported functions and associations, some of which overlap with that of alpha4beta1. This overlap led us to test the specific hypothesis that alpha4beta1 and CD14 interact directly. Jurkat T cells (alpha4beta1(+)) were found to adhere to a recombinant CD14-Fc protein via alpha4beta1, whilst K562 cells (alpha4beta1(-)) did not. However, stable reexpression of the alpha4-subunit conferred this ability. The adhesion of both cell types to CD14 displayed activation state-dependent binding very similar to the interaction of alpha4beta1 with its prototypic ligand, VCAM-1. In solid phase assays, CD14-Fc bound to affinity-purified alpha4beta1 in a dose-dependent manner that was induced by activating anti-beta1 mAbs. Finally, in related experiments, JY cells (alpha4beta7(+)) were also found to attach to CD14-Fc in an alpha4-dependent manner. In summary, CD14 is a novel ligand for alpha4beta1, exhibiting similar activation-state dependent binding characteristics as other alpha4beta1 ligands. The biological relevance of this interaction will be the subject of further studies. PMID- 17274988 TI - ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation. AB - Activation of the neuronal receptor tyrosine kinase ALK (anaplastic lymphoma kinase) promoted the neuron-like differentiation of PC12 cells through specific activation of the ERK MAP-kinase pathway. However, the nature of primary signaling events initiated is still poorly documented. Here, we established that Shc and FRS2 adaptors were recruited and phosphorylated following antibody-based ALK activation. We further demonstrated that Shc was recruited to the consensus phosphotyrosine site NPTpY(1507) and FRS2 was likely recruited to a novel non orthodox phosphotyrosine site within ALK. Finally, we characterized a functional role for Shc and likely FRS2 in ALK-dependant MAP-kinase activation and neuronal differentiation of PC12 cells. These findings hence open attractive perspectives concerning specific characteristics of ALK in the control of the mechanisms driving neuronal differentiation. PMID- 17274989 TI - TAT-BH4 counteracts Abeta toxicity on capillary endothelium. AB - Oxidative stress is one of the factor contributing to blood brain barrier degeneration. This phenomenon is observed during pathological conditions such as Alzheimer's disease or cerebral amyloid angiopathy in which brain haemorrhages are very frequent. Both diseases are characterized by beta amyloid peptide deposition either in neurons or in vessels. Oxidative stress leads to impairment of mitochondrial functions and apoptotic cell death subsequent to caspases activation. In this paper we demonstrate that BH4 domain of Bcl-xl administrated to endothelial cells as the conjugated form with TAT peptide, reverts Abeta induced apoptotic cell death by activating a survival programme which is Akt/endothelial nitric oxide synthase dependent. PMID- 17274990 TI - Metabolic profiling using combined GC-MS and LC-MS provides a systems understanding of aristolochic acid-induced nephrotoxicity in rat. AB - We present here a combined GC-MS and LC-MS metabolic profiling approach to unraveling the pathological outcomes of aristolochic acid (AA)-induced nephrotoxicity. Urine samples were analyzed by GC-MS and LC-MS in combination with pattern recognition techniques, e.g. principal component analysis (PCA), orthogonal projection to latent structure-discriminant analysis. The work indicates that AA-induced acute renal toxicity as evidenced by histopathological examinations could be characterized by systemic disturbance of metabolic network involving free fatty acids generation, energy and amino acids metabolism, and alteration in the structure of gut microbiota. Therefore, this method is potentially applicable to the toxicological study, providing a comprehensive understanding of systems response to xenobiotic intervention. PMID- 17274992 TI - Expression of leucine-rich repeat-containing G-protein-coupled receptors in the human cyclic endometrium. AB - OBJECTIVE: To study the mRNA expression of the two leucine-rich repeat-containing G-protein-coupled receptors LGR-4 and LGR-5 and the mRNA and protein expression of LGR-7, the relaxin receptor, in the human cyclic endometrium. DESIGN: Retrospective study. SETTING: Department of Anatomy and Reproductive Biology, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Germany. METHOD(S): LGR-4, -5, and -7 mRNA expression was assessed by semiquantitative and real time reverse transcription-polymerase chain reaction in the endometrium of premenopausal women (n = 26) and cultured primary endometrial epithelial cells and fibroblasts (n = 3). Transcript size was determined by Northern blotting. LGR 7 protein expression was assessed by immunohistochemistry. RESULT(S): The mRNA of LGR-4, LGR-5, and LGR-7 was expressed constitutively throughout the menstrual cycle in the endometrium, and characterized by substantial differences in expression levels of individual women. LGR-7 immunostaining was detected in the epithelium of the functional layer throughout the cycle, with lowest staining in the midproliferative phase. Furthermore, individual stromal cells of the functional layer and the stroma of the basal layer showed LGR-7 immunostaining. CONCLUSION(S): Endometrial expression of the mRNA of orphan receptors LGR-4 and LGR-5 implies that the endometrium is potentially influenced by as yet unknown mediators, which are possibly involved in fertility control. Furthermore, we confirmed constitutive endometrial mRNA expression of LGR-7, the classical relaxin receptor, and demonstrated specific LGR-7 immunostaining of different endometrial cell types, which suggests a physiological role of relaxin in the human endometrium. PMID- 17274991 TI - Endocrine profiles and neuropsychologic correlates of functional hypothalamic amenorrhea in adolescents. AB - OBJECTIVE: To determine trigger factors and neuropsychologic correlates of functional hypothalamic amenorrhea (FHA) in adolescence and to evaluate the correlations with the endocrine-metabolic profile. DESIGN: Cross-sectional comparison of adolescents with FHA and eumenorrheic controls SETTING: Academic medical institution PATIENT(S): Twenty adolescent girls with FHA (aged <18 years) and 20 normal cycling girls INTERVENTION(S): All subjects underwent endocrine gynecologic (hormone) and neuropsychiatric (tests and interview) investigations. A separate semistructured interview was also used to investigate parents. MAIN OUTCOME MEASURE(S): Gonadotropins, leptin, prolactin, androgens, estrogens, cortisol, carrier proteins (SHBG, insulin-like growth factor-binding protein 1), and metabolic parameters (insulin, insulin-like growth factor 1, thyroid hormones) were assayed in FHA and control subjects. All girls were evaluated using a test for depression, a test for disordered eating, and a psychodynamic semistructured interview. RESULT(S): Adolescents with FHA showed a particular susceptibility to common life events, restrictive disordered eating, depressive traits, and psychosomatic disorders. The endocrine-metabolic profile was strictly correlated to the severity of the psychopathology. CONCLUSION(S): Functional hypothalamic amenorrhea in adolescence is due to a particular neuropsychologic vulnerability to stress, probably related to familial relationship styles, expressed by a proportional endocrine impairment. PMID- 17274993 TI - Segregation of chromosomes in spermatozoa of four Hungarian translocation carriers. AB - OBJECTIVE: To determine the segregation pattern of the translocated chromosomes in spermatozoa of human males with translocations. DESIGN: Retrospective case control study. SETTING: Hospital-based genetic laboratory for reproductive biology. PATIENT(S): A carrier with Y-autosome reciprocal translocation, two with autosome-autosome reciprocal translocations, and one with Robertsonian translocation. INTERVENTION(S): Blood sample and sperm sample collection from each translocation carrier. MAIN OUTCOME MEASURE(S): Fluorescence in situ hybridization on lymphocyte slides to characterize each translocation case. Fluorescence in situ hybridization with specific DNA probes for each of the sperm samples to characterize the chromosomes involved in the rearrangement and to evaluate the possible interchromosomal effect for chromosomes 18, X, and Y. RESULT(S): Each translocation carrier showed a specific mode of segregation pattern of the translocated chromosomes, confirming the dependence on chromosomes involved in the translocation. The highest frequency from alternate segregation was with the carrier of Robertsonian translocation (90.9%), and the lowest was with the carrier of Y-autosome translocation (29.7%). No evidence of an interchromosomal effect for chromosomes 18, X, and Y were detected. CONCLUSION(S): Depending on the rate of the genetically normal and abnormal segregation modes, we can evaluate the chance of having a healthy proband. These results ensure more accurate genetic counseling for patients in assisted reproduction centers. PMID- 17274995 TI - Mother's timing and duration of corticosterone exposure modulate offspring size and natal dispersal in the common lizard (Lacerta vivipara). AB - Although multiple condition dependence in dispersal is common, the proximate mechanisms that integrate information from multiple sources remain largely unknown. In the common lizard (Lacerta vivipara), earlier studies have shown that maternal plasma corticosterone level interacts with maternal phenotype to affect offspring phenotype and dispersal strategy, and may reflect the mother's external and/or internal environment. However, the mechanism by which these two types of environmental information are integrated has not been identified. We explored the possibility that the timing and duration of the corticosterone signal are the key factors by which the message is modulated. We found that the timing of corticosterone exposure affects the juvenile phenotype: an exposure to corticosterone early in development has negative effects on juvenile size, weight, and body condition, that can nevertheless be restored in the case of a prolonged exposure. The duration of corticosterone exposure affects the dispersal strategy, although the precise effect depends on the sex ratio of the clutch. That is, in female-biased clutches, a prolonged exposure during gestation promotes philopatry of juveniles, while a short exposure enhances their dispersal, a result that is consistent with kin competition theory. Therefore, our results demonstrate that while corticosterone titer may signal a mother's external and/or internal environment to her developing young, differences in the timing and duration of this endocrine signal produce offspring with specialized phenotypes that exhibit different dispersal strategies. PMID- 17274994 TI - The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats. AB - Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the Sprague-Dawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women. PMID- 17274996 TI - Effects of early embryonic exposure to genistein on male copulatory behavior and vasotocin system of Japanese quail. AB - Genistein is a phytoestrogen, particularly abundant in soybeans that can bind estrogen receptors and sex hormone binding proteins, exerting both estrogenic and antiestrogenic activity. In this study we used the Japanese quail embryo as a test end-point to investigate the effects of early embryonic exposure to genistein on male copulatory behavior and on vasotocin parvocellular system. Both differentiate by the organizational effects of estradiol during development and may therefore represent an optimal model to study the effects of xenoestrogens. We injected two doses of genistein (100 and 1000 microg) into the yolk of 3-day old Japanese quail eggs. Other eggs were treated with either 25 microg of estradiol benzoate or sesame oil as positive and negative controls. At the age of 6 weeks, behavioral tests revealed a significant decrease of all aspects of copulatory behavior (in comparison to the control group) in estradiol-treated birds. In contrast, genistein-treated animals demonstrated various degrees of decrease in the mean frequencies of some aspects of the sexual behavior. The computerized analysis of vasotocin innervation in medial preoptic, stria terminalis and lateral septum nuclei revealed a statistically significant decreased immunoreactivity in treated animals compared to control ones. These results demonstrate that genistein, similarly to estradiol, has an organizational effect on quail parvocellular vasotocin system and on copulatory behavior. In conclusion, present results confirm, in this avian model, that embryonic exposure to phytoestrogens may have life-long effects on sexual differentiation of brain structures and behaviors. PMID- 17274997 TI - Release of orphanin FQ/nociceptin in the medial preoptic nucleus and ventromedial nucleus of the hypothalamus facilitates lordosis. AB - Opioid regulation of reproduction has been widely studied. However, the role of opioid receptor-like 1 receptor (NOP; also referred to as ORL-1 and OP4) and its endogenous ligand orphanin FQ/nociceptin (OFQ/N) have received less attention despite their extensive distribution throughout nuclei of the limbic-hypothalamic system, a circuit that regulates reproductive behavior in the female rat. Significantly, the expression of both receptor and ligand is regulated in a number of these nuclei by estradiol and progesterone. Activation of NOP in the ventromedial nucleus of the hypothalamus (VMH) of estradiol-primed nonreceptive female rats facilitates lordosis. NOPs are also expressed in the medial preoptic nucleus (MPN), however, their roles in reproductive behavior have not been studied. The present experiments examined the role of NOP in the regulation of lordosis in the MPN and tested whether endogenous OFQ/N in the MPN and VMH mediates reproductive behavior. Activation of NOP by microinfusion of OFQ/N in the MPN facilitated lordosis in estradiol-primed sexually nonreceptive female rats. Passive immunoneutralization of OFQ/N in either the MPN or the VMH reduced lordosis in estradiol-primed females, but had no effect on lordosis in estradiol+progesterone-primed sexually receptive rats. These studies suggest that OFQ/N has a central role in estradiol-only induced sexual receptivity, and that progesterone appears to involve additional circuits that mediate estradiol+progesterone sexual receptivity. PMID- 17274998 TI - Mifepristone and misoprostol in the induction of labor at term. AB - OBJECTIVE: To assess the ability of mifepristone to prime the cervix adequately and induce labor in pregnant women at term; and when mifepristone alone proves insufficient, to determine whether oral misoprostol taken 48 h following mifepristone administration is effective in inducing labor. METHODS: In this prospective study 50 pregnant women at term with an unfavorable cervix were given 400 mg of mifepristone orally and allowed to return home. If labor did not start within 48 h, the women were admitted and induction was continued with 50 mug of misoprostol, a prostaglandin (PG) E1 analogue, taken orally every 4 h. The 50 controls, who were matched prospectively for parity and pregnancy duration, underwent labor induction according to the routine administration of 3-mg tablets of PGE2 vaginally. RESULTS: In the study group, 66% of the women entered labor spontaneously or had a sufficiently ripened cervix within 48 h of taking mifepristone. However, there was no difference in time between prostaglandin administration and delivery between the control group and the 34% of women who required misoprostol in the study group. In the study group, the cesarean section rate was significantly lower among the women whose labor was induced with mifepristone alone than among those who required misoprostol. There were no differences overall in obstetric or neonatal outcomes between the study and control groups. CONCLUSIONS: In this pilot sample, 400 mg of mifepristone was effective in inducing cervical changes and labor. Although there were no adverse effects using oral misoprostol in combination with mifepristone, labor was more difficult to induce in the women who did not respond to mifepristone alone, and these women had a higher operative delivery rate. PMID- 17274999 TI - Maternal mortality, stillbirth and measures of obstetric care in developing and developed countries. AB - OBJECTIVE: Maternal mortality and stillbirths are important adverse pregnancy outcomes, especially in developing countries. Because underlying causes of both outcomes appeared similar, the relationship between maternal mortality, stillbirth and three measures of obstetrical care were studied. METHODS: Using data provided by the World Health Organization from 188 developed and developing countries, correlations and linear regression analyses between maternal mortality and stillbirth rates and cesarean section rates, skilled delivery attendance, and >or=4 prenatal visits) were developed. RESULTS: Stillbirth and maternal mortality rates were strongly correlated, with about 5 stillbirths for each maternal death. However, the ratio increased from about 2 to 1 in least developed countries to 50 to 1 in the most developed countries. In developing countries, as the cesarean section rates increased from 0 to about 10%, both maternal mortality and stillbirth rates decreased sharply. Skilled delivery attendance was not associated with significant reductions in maternal mortality or stillbirth rates until coverage rates of about 40% were achieved. Four or more antenatal visits were not associated with significant reductions in maternal deaths until about 60% coverage was achieved. The same measure was associated with only modest decreases in stillbirth. CONCLUSION: Across countries, stillbirth was significantly associated with maternal mortality. Both stillbirth and maternal mortality were similarly related to all three measures of obstetric care. An increase in cesarean section rates from 0 to 10% was associated with sharp decreases in both maternal mortality and stillbirths. PMID- 17275000 TI - Characterisation of the subtelomeric regions of Giardia lamblia genome isolate WBC6. AB - Giardia trophozoites are polyploid and have five chromosomes. The chromosome homologues demonstrate considerable size heterogeneity due to variation in the subtelomeric regions. We used clones from the genome project with telomeric sequence at one end to identify six subtelomeric regions in addition to previously identified subtelomeric regions, to study the telomeric arrangement of the chromosomes. The subtelomeric regions included two retroposons, one retroposon pseudogene, and two vsp genes, in addition to the previously identified subtelomeric regions that include ribosomal DNA repeats. The presence of vsp genes in a subtelomeric region suggests that telomeric rearrangements may contribute to the generation of vsp diversity. These studies of the subtelomeric regions of Giardia may contribute to our understanding of the factors that maintain stability, while allowing diversity in chromosome structure. PMID- 17275001 TI - Evidence of a species complex within the food-borne trematode Opisthorchis viverrini and possible co-evolution with their first intermediate hosts. AB - The food-borne trematodes, Opisthorchis viverrini, O. felineus and Clonorchis sinensis, have long been recognized as the cause of major human health problems, with an estimated 40 million infected persons. Of the three species of liver fluke, only O. viverrini is classified as a type 1 carcinogen because of its role as an initiator of chronic inflammation and the subsequent development of cholangiocarcinoma. At present, there are no techniques for the early diagnosis of cholangiocarcinoma and it is fatal for most patients. There is considerable variation in parasite prevalence and disease presentation in different geographical areas, the latter of which may be associated with genetic differences among parasites. In the present study, multilocus enzyme electrophoresis was used to provide a comprehensive genetic characterization of O. viverrini from different geographical localities in Thailand and the Peoples' Democratic Republic of Laos. Parasites from different localities were compared genetically at 32 enzyme loci. The results of the genetic analyses are sufficient to reject the null hypothesis that O. viverrini represents a single species. Therefore, O. viverrini consists of at least two genetically distinct, yet morphologically similar (i.e. cryptic) species. Moreover, there was also separation of the different populations of snails (i.e. the first intermediate hosts) into two distinct genetic groups that corresponded with the delineation of O. viverrini into two species. This suggests that there may be a history of co evolution in this host-parasite lineage. Additionally, five distinct genetic groups of parasites were detected, each of which occurred within a different and independent river wetland system. Our findings have major implications for the implementation of effective control and surveillance programs targeted to these medically important food-borne parasites. PMID- 17275003 TI - Genetic risk for restenosis after coronary stenting. AB - OBJECTIVES: The purpose of the present study was to identify gene polymorphisms that confer susceptibility to restenosis after bare-metal stenting of coronary arteries, and thereby to predict the genetic risk for this condition. METHODS AND RESULTS: The study population comprised 461 unrelated Japanese individuals (350 men, 111 women) who underwent stent implantation, including 107 subjects who developed in-stent restenosis and 354 subjects without this condition. The genotypes for 142 polymorphisms of 121 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariate logistic regression analysis with adjustment for the prevalence of diabetes mellitus revealed that the 1615G-->A polymorphism of BCHE, the 7,067,365C-->A polymorphism of INSR, the C-->T polymorphism of GPX1, the G-->A polymorphism of ROS1, and the G-->A polymorphism of MMP9 were associated (P<0.05) with in-stent restenosis. Further analysis with adjustment both for the prevalence of diabetes mellitus and for quantitative coronary angiographic measurements revealed that the BCHE, GPX1, and ROS1 genotypes were independently associated (P<0.05) with in-stent restenosis. CONCLUSIONS: Determination of the genotypes for BCHE, GPX1, and ROS1 may prove informative for assessment of the genetic risk for in-stent restenosis. PMID- 17275002 TI - Anatomical differences and atherosclerosis in apolipoprotein E-deficient mice with 129/SvEv and C57BL/6 genetic backgrounds. AB - There are well-known genetic background effects on atherosclerosis susceptibility in mice. To study the basis of these effects, we have generated the apolipoprotein E-null mutation in mouse embryonic stem cells of 129/SvEv origin, maintained it in the inbred strain (129-apoE), and compared these mice with those previously made in strain 129/Ola and backcrossed to a C57BL/6 genetic background (B6-apoE). Plasma cholesterol and triglyceride levels in the apoE-129 mice are twice the levels in apoE-B6, and both VLDL/chylomicron remnants and HDL particles are increased. Regression analysis of plaque size relative to the age of mice suggests that the initiation of atherosclerotic plaque development at the aortic root is slower in 129-apoE mice (intercept at 3.9 months in females and 4.1 months in males) than in B6-apoE mice (1.3 months in females and 2.8 months in males). In contrast, 129-apoE mice develop extensive plaques in the aortic arches earlier than B6-apoE mice. Distinct differences in the geometry of the aortic arch between the two strains suggest that anatomical differences may contribute to the effects of genetic background on atherosclerosis. The 129-apoE/B6-apoE pair thus provides a tool to study factors governing the relation between arterial geometry and the location of plaque development. PMID- 17275005 TI - Association between serum uric acid level and peripheral arterial disease. AB - BACKGROUND: Higher serum uric acid levels have been implicated in the development and progression of atherosclerotic cardiovascular disease. However, it is not clear whether serum uric acid levels are related to subclinical measures of cardiovascular disease, including peripheral arterial disease (PAD). We examined the association between increasing serum uric acid levels and PAD in the US general population. METHODS: A cross-sectional study was conducted among 3987 National Health and Nutrition Examination Survey 1999-2002 participants aged > or =40 years, without clinical history of cardiovascular disease. Main outcome-of interest was PAD defined as ankle-brachial index <0.9 (n=229). RESULTS: Higher serum uric acid levels were positively associated with PAD, independent of smoking, body mass index (BMI), hypertension, diabetes, serum total cholesterol, serum creatinine, and other confounders. Multivariable odds ratio (OR) [95 percent confidence intervals (CI)] comparing serum uric acid levels > or =75th percentile (> or =380.8 micromol/L) to uric acid levels <50th percentile (<315.6 micromol/L) was 1.62 (1.08-2.44), p-trend=0.015. This association persisted in separate analysis among men and women. Further, the results were consistent in subgroup analyses by categories of age, current smoking, BMI, and diabetes mellitus. CONCLUSIONS: Higher serum uric acid levels are associated with PAD in the US general population. These results suggest that PAD may be an important indicator of the reported association between higher serum uric acid levels and clinical cardiovascular disease. Future prospective studies are required to clarify the temporal nature of this relationship. PMID- 17275004 TI - Postprandial glucose and not triglyceride concentrations are associated with carotid intima media thickness in women with normal glucose metabolism: the Hoorn prandial study. AB - The present study aimed to compare the associations of postprandial glucose (ppGL) and postprandial triglycerides (ppTG) with carotid intima media thickness (cIMT) in women with normal glucose metabolism (NGM) and type 2 diabetes (DM2). Post-menopausal women (76 with NGM, 78 with DM2), received two consecutive fat rich and two consecutive carbohydrate-rich meals on separate occasions. Blood samples were taken before and 1, 2, 4, 6 and 8h following breakfast; lunch was given at t=4. Ultrasound imaging of the carotid artery was performed to measure cIMT. In women with NGM, an increase of 1.0 mmol/l glucose following the fat-rich meals was associated with a 50 microm cIMT increase (p=0.04), and following the carbohydrate meals, an increase of 1.8 mmol/l glucose was associated with a 50 microm larger cIMT (p=0.08). These associations were not explained by classical cardiovascular risk factors. However, no association between ppGL and cIMT was found in women with DM2 and ppTG were not associated with cIMT. The association between ppGL and cIMT in normoglycaemic women suggests that ppGL in the normal range is a marker or a risk factor for atherosclerosis. Postprandial glucose levels might be a better indicator of risk than post-OGTT glucose levels or triglyceride levels. PMID- 17275006 TI - alpha 8 Integrin overexpression in de-differentiated vascular smooth muscle cells attenuates migratory activity and restores the characteristics of the differentiated phenotype. AB - Loss of the differentiated (contractile) phenotype of vascular smooth muscle cells (VSMCs) heightens their migratory activity. Integrins, as the main integrators of cell-extracellular matrix, regulate different aspects of cell behavior including migration and differentiation. alpha 8 beta 1 Integrin being expressed in cell types with contractile abilities is downregulated during VSMC phenotype modulation. In this report the ability of alpha 8 beta 1 integrin to induce the characteristics of the contractile phenotype as well as suppression of VSMC migratory activity was investigated. Forced expression of alpha 8 integrin in passage-5 rat VSMCs resulted in lower migratory activity. Western blot and immunoconfocal studies revealed that alpha 8 integrin overexpression was associated with the reappearance of VSMC contractile hallmarks including upregulation of contractile markers, assembly of stress fibres, and increased number of focal adhesions. alpha 8 Integrin overexpression in fibroblast-like Rat1 cells also induced SMC-like characteristics. alpha 8 Integrin-induced reappearance of the contractile hallmarks in de-differentiated VSMCs was impaired by RhoA inhibitors. These results provide evidences that alpha 8 integrin overexpression may assist phenotype-modulated VSMCs to revert to the contractile phenotype possibly via RhoA signaling pathway. Our findings suggest a dynamic role for alpha 8 beta 1 integrin to induce contractile phenotype as well as suppression of VSMC migration, a key player during arterial stenosis. PMID- 17275007 TI - High glucose induces plasminogen activator inhibitor-1 expression through Rho/Rho kinase-mediated NF-kappaB activation in bovine aortic endothelial cells. AB - Recently, it has become evident that elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with myocardial infarction and stroke, especially in patients with diabetes. The molecular mechanisms involved in hyperglycemia-induced PAI-1 expression in bovine aortic endothelial cells (BAEC) were investigated. PAI-1 expression in BAEC was significantly increased in accordance with the concentration of glucose in media from 5.7 mM to 23 mM. Stimulation with high glucose (23 mM) significantly increased small GTPase Rho A activation. Pretreatment with a Rho-kinase inhibitor, Y-27632 (1-10 microM), significantly blocked high glucose-induced PAI-1 expression. NF-kappaB activity determined using the luciferase reporter gene assay was significantly enhanced by high glucose, and pretreatment with Y-27632 inhibited high glucose-induced PAI-1 expression at the basal level. An inhibitor of NF-kappaB action, namely parthenolide (0.1 microM), BAY 11-7082 (5 microM) and SN50 (1 microM), significantly blocked high glucose-mediated PAI-1 expression to a level with low glucose (5.7 mM). These data suggested that high glucose-induced PAI-1 expression in endothelial cells is mediated by NF-kappaB activation through the Rho/Rho kinase pathway. Inhibition of Rho/Rho-kinase signaling might be a novel target for diabetes and metabolic syndrome. PMID- 17275008 TI - Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis. AB - OBJECTIVE: There is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ultrasound evidence of early atherosclerosis in the context of vascular risk factors. DESIGN: A case-control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls. METHODS: We assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT. RESULTS: The common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08-8.38%], p<0.0001) or 0.044 mm [0.021-0.066 mm] (p=0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% [19.5-29.4%] or 0.250 mm [0.198-0.303 mm] higher in HIV patients (p<0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART). CONCLUSIONS: HIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4-14% greater and the "vascular age" 4-5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified. PMID- 17275009 TI - Increased cholesterol efflux from cultured fibroblasts to plasma from hypertriglyceridemic type 2 diabetic patients: roles of pre beta-HDL, phospholipid transfer protein and cholesterol esterification. AB - We tested whether hypertriglyceridemia associated with type 2 diabetes mellitus is accompanied by alterations in pre beta-HDL, which are considered to be initial acceptors of cell-derived cholesterol, and by changes in the ability of plasma to promote cellular cholesterol efflux. In 28 hypertriglyceridemic and 56 normotriglyceridemic type 2 diabetic patients, and in 56 control subjects, we determined plasma lipids, HDL cholesterol and phospholipids, plasma pre beta-HDL and pre beta-HDL formation, phospholipid transfer protein (PLTP) activity, plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) and the ability of plasma to stimulate cholesterol efflux out of cultured human fibroblasts. HDL cholesterol and HDL phospholipids were lower, whereas plasma PLTP activity, EST and CET were higher in hypertriglyceridemic diabetic patients than in the other groups. Pre beta-HDL levels and pre beta-HDL formation were unaltered, although the relative amount of pre beta-HDL (expressed as % of total plasma apo A-I) was increased in hypertriglyeridemic diabetic patients. Cellular cholesterol efflux to plasma from hypertriglyceridemic diabetic patients was increased compared to efflux to normotriglyceridemic diabetic and control plasma, but efflux to normotriglyceridemic diabetic and control plasma did not differ. Multiple linear regression analysis demonstrated that cellular cholesterol efflux to plasma was positively and independently related to pre beta-HDL formation, PLTP activity and EST (multiple r=0.48), but not to the diabetic state. In conclusion, cholesterol efflux from fibroblasts to normotriglyceridemic diabetic plasma is unchanged. Efflux to hypertriglyceridemic diabetic plasma is enhanced, in association with increased plasma PLTP activity and cholesterol esterification. Unaltered pre beta-HDL formation in diabetic hypertriglyceridemia, despite low apo A-I, could contribute to maintenance of cholesterol efflux. PMID- 17275010 TI - Advantages and limitations of on-line solid phase extraction coupled to liquid chromatography-mass spectrometry technologies versus biosensors for monitoring of emerging contaminants in water. AB - On-line solid phase extraction (SPE) coupled to liquid chromatography-mass spectrometry (LC-MS) and biosensors are advanced technologies that have found increasing application in the analysis of environmental contaminants although their application to the determination of emerging contaminants (previously unknown or unrecognized pollutants) has been still limited. This review covers the most recent advances occurred in the areas of on-line SPE-LC-MS and biosensors, discusses and compares the main strengths and limitations of the two approaches, and examines their most relevant applications to the analysis of emerging contaminants in environmental waters. So far, the on-line configuration most frequently used has been SPE coupled to liquid chromatography-(tandem) mass spectrometry. Sorbents used for on-line SPE have included both traditional (alkyl bonded silicas and polymers) and novel (restricted access materials (RAMs), molecularly imprinted synthetic polymers (MIPs), and immobilized receptors or antibodies (immunosorbents) materials. The biosensor technologies most frequently applied have been based on the use of antibodies and, to a lesser extent, enzymes, bacteria, receptors and DNA as recognition elements, and the use of optical and electrochemical transducing elements. Emerging contaminants investigated by means of these two techniques have included pharmaceuticals, endocrine disrupting compounds such as estrogens, alkylphenols and bisphenol A, pesticides transformation products, disinfection by-products, and bacterial toxins and mycotoxins, among others. Both techniques offer advantageous, and frequently comparable, features such as high sensitivity and selectivity, minimum sample manipulation, and automation. Biosensors are, in addition, relatively cheap and fast, which make them ideally suited for routine testing and screening of samples; however, in most cases, they can not compete yet with on-line SPE procedures in terms of accuracy, reproducibility, reliability (confirmation) of results, and capacity for multi-analyte determination. PMID- 17275011 TI - Limits of the numerical estimation of the adsorption energy distribution from adsorption isotherm data using the expectation-maximization method. AB - The limits of the use of the expectation-maximization (EM) method for the study of the heterogeneity of adsorbent surfaces were tested by calculating the adsorption energy distribution of systems having known degrees of heterogeneity. Connecting on-line two different columns allows the simulation of a heterogeneous system. The two columns used were endcapped, C(18)-bonded silica used as stationary phases and having different degrees of C(18) chain coverages (0.42 and 2.03 micromol/m(2)). The adsorption constants of phenol measured by frontal analysis (FA) are significantly different on these two columns. On each column, the adsorption behavior was best accounted for by a bi-Langmuir isotherm model, corresponding to a heterogeneous surface with a bimodal energy distribution. The difference between the adsorption energies on the weak adsorption sites of the two columns is 1.5 kJ/mol. The energy difference of their high energy sites is 2.2 kJ/mol. The EM method can readily distinguish between adsorption sites having energies that differ by more than 5 kJ/mol after more than 10 million iterations, but it cannot distinguish between adsorption sites for which this energy difference is less than 2 kJ/mol, even after 100 million iterations. For highly heterogeneous systems, (e.g., those with more than three different types of adsorption sites), the EM program does not converge necessarily towards the actual energy distribution function but toward a simpler one, having fewer adsorption sites that are almost equally spaced in the energy space. This failure of the EM program is related to the fact that, despite the excellent precision of the FA measurements (<1%), any series of adsorption data can be represented by several distinct AEDs. Thus, the degree of heterogeneity of RPLC adsorbents determined with the EM method might often be minimized, resulting in erroneous values of the isotherm parameters. PMID- 17275012 TI - Enantiomeric separation of several antimycotic azole drugs using supercritical fluid chromatography. AB - The chiral resolution of four antifungal compounds, three imidazoles (miconazole, econazole and sulconazole) and one triazole (itraconazole) using supercritical fluid chromatography on the amylose-based chiral stationary phase Chiralpak AD, is presented in this work. The influence of pressure, type and percentage of organic modifier and temperature on retention times and resolution was studied. The enantiomeric separation of the three imidazoles was achieved with resolutions higher than two and analysis times lower than 10 min, obtaining the best results using methanol as modifier. However, the analysis time of the triazole was higher than 80 min due to the existence of a high number of functional groups that were able to interact with the chiral stationary phase. In this case, the resolution of the four stereoisomers was achieved only partially with mixtures of ethanol and 2-propanol as modifier. The isoenantioselective temperatures were obtained from the study of the influence of the temperature, they were above the range of temperatures assayed, except for sulconazole using 2-propanol. PMID- 17275013 TI - Advective flow in spherical floc. AB - Numerous structural models of flocs, such as homogeneous model or radially varying model, were proposed in literature for predicting the extent of advective flow on the intrafloc transport processes. This work probed the three-dimensional structure of original and chemically flocculated wastewater flocs using the fluorescence in situ hybridization (FISH) and the confocal laser scanning microscope (CLSM) techniques, from which the spherical mesh model on real floc structure was constructed. Simulation results revealed that if an average characteristic of sludge floc, such as porosity or drag force correction factor of sludge floc is of concern, both homogeneous or radially-varying models may be able to apply, particularly for those flocs that were closely compacted. However, the detailed flow patterns inside real floc are much more tortuous than those of the homogeneous or radially-varying models. If local hydrodynamic environment within the floc is of interest, then only the complicated structural model with real floc could be applicable. PMID- 17275015 TI - Rheology and orientational distributions of rodlike particles with magnetic moment normal to the particle axis for semi-dense dispersions (analysis by means of mean field approximation). AB - We have considered a semi-dense dispersion composed of ferromagnetic rodlike particles with a magnetic moment normal to the particle axis to investigate the rheological properties and particle orientational distribution in a simple shear flow as well as an external magnetic field. We have adopted the mean field approximation to take into account magnetic particle-particle interactions. The basic equation of the orientational distribution function has been derived from the balance of the torques and solved numerically. The results obtained here are summarized as follows. For a very strong magnetic field, the magnetic moment of the rodlike particle is strongly restricted in the field direction, so that the particle points to directions normal to the flow direction (and also to the magnetic field direction). This characteristic of the particle orientational distribution is also valid for the case of a strong particle-particle interaction, as in the strong magnetic field case. To the contrary, for a weak interaction among particles, the particle orientational distribution is governed by a shear flow as well as an applied magnetic field. When the magnetic particle particle interaction is strong under circumstances of an applied magnetic field, the magnetic moment has a tendency to incline to the magnetic field direction more strongly. This leads to the characteristic that the viscosity decreases with decreasing the distance between particles, and this tendency becomes more significant for a stronger particle-particle interaction. These characteristics concerning the viscosity are quite different from those for a semi-dense dispersion composed of rodlike particles with a magnetic moment along the particle direction. PMID- 17275014 TI - Effect of chain length and charge density on the construction of polyelectrolyte multilayers on colloidal particles. AB - Two combinations of sodium poly(4-styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) of different chain length and charge density are employed to construct multilayer films. The polyelectrolytes are assembled layer-by-layer on colloidal particles in the absence of salt. We have investigated the formation and electrical characteristics of the films by using electric light scattering technique. The results show that the film thickness is independent of the chain length when fully charged PAH (at pH 4.6) is combined with fully charged PSS. When the films are prepared with less charged PAH (at pH 6.7) and fully charged PSS, lower thickness is found for the film with shorter polymer chains. In all cases, the thickness increment realized on addition of the polymer with lower molar concentration is partially lost on exposure to the solution with higher concentration of the oppositely charged partner. When the film growth is regular (at equal molar concentrations of the fully charged polyelectrolytes), the ratio of PSS to PAH charge, estimated from the electro-optical effect values, exceeds 1. The electro-optical effect is also higher for the films ending with PSS when fully charged PSS is combined with less charged PAH (at pH 6.7). This reveals the key role of the charge in the last-adsorbed layer for the electro-optical behavior of the whole film. PMID- 17275016 TI - Surface characterization of hydroxyapatite: potentiometric titrations coupled with solubility measurements. AB - The acid-base properties of synthetically prepared and well-characterized hydroxyapatite (HAP) in contact with KNO3 solutions were investigated at 25 degrees C, through potentiometric titrations, zeta-potential measurements, and surface complex modeling. Aliquots of suspension were withdrawn every 0.5 pH unit during the titration procedure and analyzed for calcium and phosphate. It was found that, even for rapid titration experiments, a remarkable amount of H+ ions (H+dissol.) is consumed in the bulk solution in reacting with species coming from the dissolution of HAP. These H+ ions must be taken into account in the H+ mass balance, in order for true value for the point of zero charge (pzc=6.5+/-0.2) and consequently true value for the surface charge (sigma0) to be obtained. Besides the conventional potentiometric titration technique, it was found that pzc may be determined much more easily as the intersection point of the suspension titration curve and the blank one modified to include the amount of H+dissol. obtained at one ionic strength. Finally, a surface complexation model was proposed for the development of surface charge. Experimental data were satisfactorily fitted by using the value of 4.2 F m-2 for the capacitance. PMID- 17275017 TI - Formation and stability of a suspended biomimetic lipid bilayer on silicon submicrometer-sized pores. AB - We report the fabrication of a thin silicon membrane with an array of micrometer and submicrometer pores that acts as a scaffold for suspending a lipid bilayer. We successfully deposited a lipid bilayer by the Langmuir-Blodgett method on a synthetic silicon membrane bearing arrays of pores with sizes of 1000, 650, and 300 nm. Topographic images obtained by AFM showed a suspended lipid film spanning the pores, whatever the pore size. Higher stability of bilayers supported on smaller pores was shown by AFM characterization. These results represent an important first step to creating a biomimetic environment to study cell membrane dynamics and/or in developing a biosensor. PMID- 17275018 TI - Surface acid-base properties and hydration/dehydration mechanisms of aluminum (hydr)oxides. AB - In this paper, surface physiochemical properties of three typical aluminas, gamma Al(OH)3, gamma-Al2O3, and alpha-Al2O3, were investigated by means of XRD, SEM, TEM, BET surface area, TG/DTA, and potentiometric titration techniques. Based on the titration data, surface protonation and deprotonation constants were determined using the constant capacitance model (CCM). The emphasis of this research was laid on the comparison of the crystal structure, surface hydration/dehydration and acid-base properties of these three typical alumina minerals. The calculation results revealed that the surface acidity of the aluminas is in the order of alpha-Al2O3>gamma-Al(OH)3>gamma-Al2O3 after being hydrated for 1 h. The correlation between the hydration/dehydration mechanisms of alumina and its acid/base properties is discussed. PMID- 17275019 TI - Flow cytometry for basophil activation markers: the measurement of CD203c up regulation is as reliable as CD63 expression in the diagnosis of cat allergy. AB - The flow cytometric basophil activation test (BAT), based on the detection of allergen-induced CD63 expression, has been proved effective in the diagnosis of various IgE-mediated allergies. However, there is not yet consensus about the suitability of CD203c expression as a specific basophil activation marker and its diagnostic reliability. The goal of the present study was to compare measurement of CD63 and CD203c expression using BAT in a model of cat allergy and to determine optimal experimental conditions for both markers. Heparinized whole blood samples from 20 cat allergic patients and 19 controls were incubated with Fel d1 (relevant allergen) or anti-FcepsilonRI (positive control) either in IL-3 or IL-3-free conditions. An optimal gating of basophils was achieved in triple staining protocols: anti-IgE PE/anti-CD45 PerCP/anti-CD63 FITC or anti-IgE FITC/anti-CD45 PerCP/anti-CD203c PE. We demonstrated that IL-3 significantly enhanced CD63-induced expression by basophils obtained from cat allergic patients in response to Fel d1. Sensitivity was found to be 100%. The CD203c protocol, when performed under IL-3-free conditions, also demonstrated 100% sensitivity. Only one of the control subjects was positive in both tests. In conclusion, using well-defined experimental conditions, the measurement of CD203c up-regulation on basophils in response to specific allergens is as reliable as CD63-BAT for the in vitro diagnosis of patients with IgE-mediated allergy. PMID- 17275020 TI - Molecular and reverse genetic characterization of serine proteinase-induced hemolysis in the midgut of the ixodid tick Haemaphysalis longicornis. AB - Enzyme-induced hemolysis has been shown to occur in the midgut of ticks; however, little is known about the molecular basis for hemolytic activity. We report here the molecular and reverse genetic characterization of a hemolytic midgut serine proteinase, HlSP, recently identified from the ixodid tick Haemaphysalis longicornis. Endogenous HlSP was found in the midgut lumen and its contents, indicating that HlSP is extracellularly secreted. Recombinant H. longicornis serine proteinase (rHlSP) expressed in Escherichia coli showed dose-dependent hemolytic activity towards rabbit erythrocytes, with a maximum hemolysis of 94.5% within 1 h in vitro. Tests of pH dependency showed that rHlSP displayed optimal activity at pH 6.0. In binding assays, rHlSP showed high affinity to band 3, which shares the major erythrocyte membrane proteins. Disruption of HlSP-specific mRNA by RNA interference resulted in inhibition of the degradation of host erythrocyte membranes by endogenous HlSP in the knock-down ticks, indicating that HlSP plays a crucial role in the hemolysis in the midgut of haematophagous ticks. Our results suggest that HlSP may be essential for initiating the proteolytic cascade for the degradation of the host blood-meal. PMID- 17275021 TI - Promotion of cardiac hypertrophy by TRPC-mediated calcium entry. PMID- 17275022 TI - The principal motions involved in the coupling mechanism of the recovery stroke of the myosin motor. AB - Muscle contraction is driven by a cycle of conformational changes in the myosin II head. After myosin binds ATP and releases from the actin fibril, myosin prepares for the next power stroke by rotating back the converter domain that carries the lever arm by 60 degrees . This recovery stroke is coupled to the activation of myosin ATPase by a mechanism that is essential for an efficient motor cycle. The mechanics of this coupling have been proposed to occur via two distinct and successive motions of the two helices that hold the converter domain: in a first phase a seesaw motion of the relay helix, followed by a piston like motion of the SH1 helix in a second phase. To test this model, we have determined the principal motions of these structural elements during equilibrium molecular dynamics simulations of the crystallographic end states of the recovery stroke by using principal component analysis. This reveals that the only principal motions of these two helices that make a large-amplitude contribution towards the conformational change of the recovery stroke are indeed the predicted seesaw and piston motions. Moreover, the results demonstrate that the seesaw motion of the relay helix dominates in the dynamics of the pre-recovery stroke structure, but not in the dynamics of the post-recovery stroke structure, and vice versa for the piston motion of the SH1 helix. This is consistent with the order of the proposed two-phase model for the coupling mechanism of the recovery stroke. Molecular movies of these principal motions are available at http://www.iwr.uni-heidelberg.de/groups/biocomp/fischer. PMID- 17275023 TI - Solution structure, divalent metal and DNA binding of the endonuclease domain from the replication initiation protein from porcine circovirus 2. AB - Circoviruses are the smallest circular single-stranded DNA viruses able to replicate in mammalian cells. Essential to their replication is the replication initiator, or Rep protein that initiates the rolling circle replication (RCR) of the viral genome. Here we report the NMR solution three-dimensional structure of the endonuclease domain from the Rep protein of porcine circovirus type 2 (PCV2), the causative agent of postweaning multisystemic wasting syndrome in swine. The domain comprises residues 12-112 of the full-length protein and exhibits the fold described previously for the Rep protein of the representative geminivirus tomato yellow leaf curl Sardinia virus. The structure, however, differs significantly in some secondary structure elements that decorate the central five-stranded beta sheet, including the replacement of a beta-hairpin by an alpha-helix in PCV2 Rep. The identification of the divalent metal binding site was accomplished by following the paramagnetic broadening of NMR amide signals upon Mn(2+) titration. The site comprises three conserved acidic residues on the exposed face of the central beta-sheet. For the 1:1 complex of the PCV2 Rep nuclease domain with a 22mer double-stranded DNA oligonucleotide chemical shift mapping allowed the identification of the DNA binding site on the protein and aided in constructing a model of the protein/DNA complex. PMID- 17275025 TI - Dynamics of conformational changes of Arabidopsis phototropin 1 LOV2 with the linker domain. AB - Conformational changes of Arabidopsis phot1-LOV2 with the linker (phot1-LOV2 linker) were investigated from the viewpoint of the changes in molecular volume and molecular diffusion coefficient (D) by time-resolved transient grating (TG) and transient lens (TrL) methods. Although the absorption spectrum change completes within a few microseconds, the D-value detected by the TG method decreased drastically with a time constant of 1.0 ms from 9.2(+/-0.4)x10(-11) m(2)/s to 5.0(+/-0.3)x10(-11) m(2)/s. This time-dependent D was interpreted in terms of the unfolding of alpha-helices in the linker region. The change of the alpha-helices was confirmed by observing the recovery of the circular dichroism intensity. The TrL signal showed that the molecular volume decreases with two time constants; 300 micros and 1.0 ms. The former time constant is close to the previously observed photo-dissociation reaction rate of the phot1-LOV2 (without the linker) dimer, and the latter one agrees well with the rate of the D-change. Considering a similar time constant of the dissociation reaction of the LOV2 dimer, we interpreted these kinetics in terms of the dissociation step of the linker region from the LOV2 domain (T(390)(pre) state). After this step, the protein volume and D are decreased significantly with the lifetime of 1.0 ms. The D decrease indicates the increase of the intermolecular interaction between the protein and water molecules. On the basis of these observations, a two-step mechanism of the linker unfolding is proposed. PMID- 17275026 TI - Multimedia educational aids for improving consumer knowledge about illness management and treatment decisions: a review of randomized controlled trials. AB - Psychiatric practice is becoming increasingly more complex in terms of the available treatment options, use of new technologies for assessments, and a need for psychiatric patients and their caregivers to be familiar with general medical procedures. This trend will only intensify in the years to come. Routine methods of providing information relevant to clinical decision making about healthcare evaluations or management are often suboptimal. Relatively little research has been done on enhancing the capacity of psychiatric patients and the caregivers to make truly informed decisions about management. In this paper, we review studies that compared the effects of multimedia (video- or computer-based) educational aids with those of routine procedures to inform healthcare consumers about medical evaluations or management. Although most of these investigations were conducted in non-psychiatric patients, the results should be relevant for psychiatric practice of tomorrow. We searched MEDLINE, PsycINFO, and CINAHL bibliographic databases. Randomized controlled trials that used objective measures of knowledge or understanding of the information provided were selected. Studies were rated as positive if the multimedia educational aid resulted in a greater improvement in knowledge or understanding than the control condition. The quality of each study was also rated using a newly developed Scale for Assessing Scientific Quality of Investigations (SASQI). A total of 37 randomized controlled trials were identified. Nearly two-thirds of the studies (23/37) in diverse patient populations and for varied medical assessments and treatments reported that multimedia educational aids produced better understanding of information compared to routine methods. SASQI scores for the positive and negative studies were comparable, suggesting that lower quality was not related to positive findings. In conclusion, multimedia educational aids hold promise for improving the provision of complex medical information to patients and caregivers. It is likely that as psychiatric patients and their treating clinicians face increasingly complex choices regarding mental health treatment, multimedia decisional aids could become an effective supplement to the clinician patient interaction in near future. PMID- 17275024 TI - Fis targets assembly of the Xis nucleoprotein filament to promote excisive recombination by phage lambda. AB - The phage-encoded Xis protein is the major determinant controlling the direction of recombination in phage lambda. Xis is a winged-helix DNA binding protein that cooperatively binds to the attR recombination site to generate a curved microfilament, which promotes assembly of the excisive intasome but inhibits formation of an integrative intasome. We find that lambda synthesizes surprisingly high levels of Xis immediately upon prophage induction when excision rates are maximal. However, because of its low sequence-specific binding activity, exemplified by a 1.9 A co-crystal structure of a non-specifically bound DNA complex, Xis is relatively ineffective at promoting excision in vivo in the absence of the host Fis protein. Fis binds to a segment in attR that almost entirely overlaps one of the Xis binding sites. Instead of sterically excluding Xis binding from this site, as has been previously believed, we show that Fis enhances binding of all three Xis protomers to generate the microfilament. A specific Fis-Xis interface is supported by the effects of mutations within each protein, and relaxed, but not completely sequence-neutral, binding by the central Xis protomer is supported by the effects of DNA mutations. We present a structural model for the 50 bp curved Fis-Xis cooperative complex that is assembled between the arm and core Int binding sites whose trajectory places constraints on models for the excisive intasome structure. PMID- 17275027 TI - Estimating the contributions of speeding and impaired driving to insurance claim cost. AB - INTRODUCTION: Logistic regression modelling of crash counts likely associated with speeding and impaired driving was earlier found [Zheng, Y., Cooper, P. J., & Dean, C. B. (2007). Modeling the contribution of speeding and impaired driving to insurance claim counts and costs when contributing factors are unknown. Journal of Safety Research, 38(1)] to successfully predict known outcomes in a series of simulations, but the same types of models did not accurately predict average crash costs. The aim of the study reported here was to develop a means to adjust classification model results that would improve their cost-predicting efficiency. METHOD: A classification modelling process was adjusted at the back-end using non linear optimization to rationalize the classified proportions with the true proportions when the model was applied to representative subsets of the training data. Corrections were developed to account for cost (severity) differences arising from the classification process that were not due to true variations. The process was then applied to insurance claim test data where crash contributors were unknown. RESULTS: The optimization and severity correction procedure resulted in substantial improvement in average crash cost prediction for both impaired and unsafe speed collision involvements. The error measured against true values in 20 simulations was about half for the adjusted classification model of what it was for either unadjusted classification or logistic regression models. CONCLUSIONS: Non-linear optimization of classification matrices appears to be a workable tool for improving the predictive efficiency of models where desired outcomes represent average characteristics of records as compared to simple counts or proportions. IMPACT ON INDUSTRY: Using the methodology on a full-year of insurance claim data indicated that reliance on police-reported records alone would have underestimated the total cost of unsafe speed and impaired crashes by about 40%. Since most jurisdictions use police data to base policy decisions and set program spending around such safety issues, this finding has important implications. PMID- 17275028 TI - A challenge to the assumed generalizability of prediction and countermeasure for risky driving: different factors predict different risky driving behaviors. AB - In road safety, it may be debated whether all risky behaviors are sufficiently similar to be explained by similar factors. The often assumed generalizability of the factors that influence risky driving behaviors has been inadequately tested. Study 1 (N=116) examined the role of demographic, personality and attitudinal factors in the prediction of a range of risky driving behaviors, for young drivers. Results illustrated that different driving behaviors were predicted by different factors (e.g., speeding was predicted by authority--rebellion, while drink driving was predicted by sensation seeking and optimism bias). Study 2 (N=127) examined the generalizability of these results to the general driving population. Study 1 results did not generalize. Predictive factors remained behavior-specific, but different predictor-behavior relationships were observed in the community sample. Overall, results suggest that future research and practice should focus on a multi-factor framework for specific risky driving behaviors, rather than assuming generalizability across behaviors and driving populations. PMID- 17275029 TI - Does a one-day course influence surgeon adoption of laparoscopic ventral herniorrhaphy? AB - BACKGROUND: New laparoscopic techniques introduced after residency have created a new teaching paradigm focused on animate courses and preceptor instruction. The aim of this study was to test the effectiveness of animate course instruction in teaching laparoscopic ventral hernia repair (LVHR), its success in relationship to the course participants' previous minimally invasive surgery experience, and the role of preceptors in adapting these techniques. METHODS: Surgeons participating in a one-day LVHR course (lectures/animal laboratory) at the Carolinas Medical Center were surveyed concerning professional demographics, prior laparoscopic experience, and their performance of LVHR before and after the encounter. Standard statistics were used to determine significance (P<0.05). RESULTS: Of the 234 surgeons attending a LVHR course between 1999 and 2004, 171 (73%) answered the survey. Mean follow-up after the course was 427 days (range: 34-1202 d). Mean age was 45.9 years (range: 28-67 y). Mean time since residency was 14.4 years (range: 0.5-37 y), and 106 (62%) had learned at least basic laparoscopy in residency. One hundred twenty-six (73.7%) were in private practice. Since the course, 122 (71.3%) had performed a LVHR. They had performed a total of 2049 LVHRs (mean: 16.5; range: 1-102) compared with 1098 open herniorrhaphies (mean: 9; range: 1-23). There was no difference between those performing and not performing LVHR or the number executed with respect to practice type (P=0.67), age (P=0.47), years in practice (P=0.19), or laparoscopic experience in residency (P=0.42). Fifty-four (32%) surgeons had been precepted, and all have since performed LVHR. Surgeons with advanced laparoscopic experience were more likely to perform LVHR compared with those with only laparoscopic cholecystectomy experience (87% versus 33%, P=0.02). Indeed, of those with only laparoscopic cholecystectomy experience who performed LVHR, 80% were precepted. In the subset of surgeons who had not yet performed LVHR, 28 intended to start, 17 requested assistance, and 4 planned not to begin. CONCLUSIONS: A one-day course impacts surgeon practice patterns despite age or type of practice. Surgeons with advanced laparoscopic skills are more likely to perform LVHR. Most with limited experience will begin after working with a preceptor. Didactic instruction and a precepted experience may determine the future performance of advanced laparoscopy. PMID- 17275031 TI - Vasoactive intestinal peptide inhibits adhesion molecule expression in activated human colon serosal fibroblasts by preventing NF-kappaB activation. AB - BACKGROUND: Stricture formation in Crohn's disease (CD) occurs as a result of persistent intestinal inflammatory activation, which leads to enhanced adhesion molecule expression in serosal fibroblasts (SFs). Vasoactive intestinal peptide (VIP) has anti-inflammatory and immunoregulatory properties. Treatment with VIP prevents experimental CD in animal models at the clinical and pathologic levels. The present study reports the effect of VIP on the expression of intracellular adhesion molecule-1 (ICAM-1) in IL-1beta-stimulated human colon SFs. MATERIALS AND METHODS: Primary human colon SFs were incubated with or without IL-1beta (10 ng/mL) in the presence or absence of VIP at various concentrations (0.1 to 100 nM) for designated time. Cell surface and cytosolic ICAM-1 expression were evaluated by flow cytometry and Western blot analysis, respectively. The DNA binding capacity of NF-kappaB was analyzed by electrophoretic mobility shift assay. The phosphorylation of IkappaB-alpha was examined by Western blot analysis. RESULTS: VIP inhibited IL-1beta-induced expression of ICAM-1 in a dose dependent manner. The IL-1beta-induced ICAM-1 was also inhibited by a potent inhibitor of NF-kappaB, MG132. VIP also decreased IL-1beta-induced NF-kappaB DNA binding capacity and phosphorylation of IkappaB-alpha. CONCLUSION: VIP has an inhibitory effect on IL-1beta-induced ICAM-1 expression in SFs, which may be associated with NF-kappaB activity. This may make VIP potentially a novel therapeutic agent for preventing stricture formation in Crohn's disease. PMID- 17275030 TI - A novel dendritic cell-based cancer vaccine produces promising results in a syngenic CC-36 murine colon adenocarcinoma model. AB - BACKGROUND: This study was conducted to test the efficacy of a new cancer vaccine, composed of dendritic cells (DCs) pulsed with an interleukin-2 gene encoded vaccinia virus tumor oncolysate (DC-IL-2VCO) in a CC-36 murine colon adenocarcinoma model. MATERIALS AND METHODS: CC-36 tumor cells were injected subcutaneously into the left flank of four- to six-week old male BALB/c mice. The mice were divided into three groups, each of which received one of the following treatments: (1) DCs pulsed with the IL-2 gene-encoded vaccinia oncolysate (DC-IL 2VCO), (2) DCs pulsed with the tumor oncolysate alone (DC-CO), or (3) no treatment (control). Tumor incidence was measured, and survival rates were compared using a paired Student's t-test. Cytolytic T cell activity was measured in peripheral blood lymphocytes (PBL) and splenic lymphocytes using a (51)Cr release assay. Lastly, mice were depleted of either CD4+ or CD8+ lymphocytes prior to receiving the vaccine to test the mechanism of tumor immunity in these mice. RESULTS: Mice treated with DC-IL-2VCO demonstrated decreased tumor burden, increased survival, and greater cytolytic activity compared with control mice and mice receiving DC-CO. In addition, mice depleted of CD8+ T cells prior to immunization with IL-2VV + DC-IL-2VCO had a significant increase in the incidence of tumor, similar to the untreated control mice. CONCLUSIONS: DCs pulsed with an IL-2 gene-encoded vaccinia virus tumor oncolysate (DC-IL-2VCO) produced safe and effective immune responses in a murine CC-36 colon adenocarcinoma model. This vaccine (DC-MelVac; Patent no. 11221/5) has the potential to treat humans with cancer, and has received FDA approval for use in Phase I clinical trials. PMID- 17275032 TI - Estrogen receptor beta/alpha ratio predicts response of pancreatic cancer cells to estrogens and phytoestrogens. AB - BACKGROUND: Reports on hormone receptor expression of pancreatic cancer (PaCa) cells and treatment responses to antihormonal therapy are conflicting. We examined estrogen receptor (ER) expression in PaCa cells and investigated its function in estrogen-mediated cell proliferation. METHODS: Protein levels of ERalpha and ERbeta in 8 human PaCa lines were detected by Western blot analysis. Cell proliferation was measured by sulforhodamine B analysis. ER modulators included diethylstilbestrol (DES), estradiol (E2), 4-hydroxytamoxifen (Tam), genistein (Gen), and Coumestrol (Coum). RESULTS: ERalpha levels were detected in all eight, and ERbeta in seven cell lines. ERbeta/ERalpha ratio ranged from 0.4 to 111 (median: 6.4, >5 in seven lines). Median maximal growth stimulation (in %, observed at 20 to 200 nM) was 19 (DES), 39 (E2), 20 (Tam), 22 (Gen), and -9 (Coum); median maximal inhibition (at 40 to 60 microM) was 59 (DES), 36 (E2), 25 (Tam), 43 (Gen), and 50 (Coum). The extent of E2 and Gen stimulatory effects correlated with the ERbeta/ERalpha ratio (Kendall's tau: 0.714, P = 0.024), but not ERalpha or ERbeta levels alone. Only Coum-induced inhibition correlated with the ERbeta/ERalpha ratio (P = 0.006) and with ERalpha expression (r = 0.753, P = 0.03). Gemcitabine-induced PaCa cytotoxicity (at IC(40)) was significantly reduced by E2, Gen, and Coum. CONCLUSIONS: PaCa proliferation in vitro is highly estrogen sensitive, and in contrast to other reports, ERs are frequently expressed. In 7/8 cell lines, ERbeta expression outweighs ERalpha expression. The impact of the ERbeta/ERalpha ratio on estrogen-mediated growth stimulation and reduced cytotoxicity at physiological concentrations may have clinical implications on PaCa therapy. PMID- 17275034 TI - Retained foreign bodies after surgery. AB - BACKGROUND: Medical errors during surgery are not well studied. To define risk factors associated with this type of error, we performed a case control analysis. METHODS: We retrospectively reviewed medical records involving the ICD-9 code (998.4) for unintentional foreign object remaining in the body during surgery and incident reports gathered by the Department of Risk Management over a 10 year period from 1996 to 2005. Thirty cases were matched with at least four randomly selected controls (131 control patients) that underwent the same type of operation during the same time period. RESULTS: Thirty patients had retained foreign objects (52% sponges and 43% instruments). The abdominal cavity was most commonly involved (46%) followed by the thoracic cavity (23%) although no body cavity remained uninvolved. Eight patients required readmission (30%), 25 patients required reoperation (83%), and there was no mortality. When compared with controls, patients with retained foreign objects were more likely to have had a greater number of major surgical procedures at the same time (2.7 versus 1.8, P=0.004), to have multiple surgical teams (13% versus 2%, P=0.02), and more likely to have had an incorrect instrument/sponge count recorded (13% versus 2%, P=0.01). In multivariate analysis, factors associated with a significantly higher risk of retained foreign objects were the total number of major procedures performed [odds ratio 1.6; 95% confidence interval (CI), 1.1-2.3; P=0.008] and an incorrect count (odds ratio 16.2; 95% CI, 1.3-197.8; P=0.02). CONCLUSION: Retained foreign objects after surgery are associated with multiple major surgical procedures being performed at the same time and an incorrect instrument or sponge count. Identification of these risk factors using case-control analysis should influence operating room policy and reduce these types of errors. PMID- 17275033 TI - Adapting to a new system of surgical technologies and perioperative processes among clinicians. AB - PURPOSE: To understand learning and adaptation to a new system of surgical technologies and perioperative processes. METHODS: Patient wait time, flow time, and surgery procedure time were recorded in the experimental ("Operating room of the future" or ORF) and control ORs over the first year of the ORF's operation. Regression methods were used to examine factors hypothesized to influence performance. RESULTS: Flow time, wait time, and surgery procedure time for each case decreased significantly in the ORF. The ORF performance demonstrated an initial overshoot followed by oscillation with 30-40 d period around the group mean. Similar behavior was observed for surgeons if they had >or=2-week hiatus from operating and had an average caseload more than 2.1 cases/week. Regression models using hypothesized learning factors predicted flow time (R(2)=0.33) and wait time (R(2)=0.36); adding procedure type to these models raised R(2) to 0.7 and 0.57, respectively. CONCLUSIONS: Objective observation of system performance in which a new technology is introduced can provide insights into adaptation and may have significant implications for OR scheduling, training, and cost effectiveness evaluations. PMID- 17275035 TI - Molecular seismology: an inverse problem in nanobiology. AB - The density profile of an elastic fiber like DNA will change in space and time as ligands associate with it. This observation affords a new direction in single molecule studies provided that density profiles can be measured in space and time. In fact, this is precisely the objective of seismology, where the mathematics of inverse problems have been employed with success. We argue that inverse problems in elastic media can be directly applied to biophysical problems of fiber-ligand association, and demonstrate that robust algorithms exist to perform density reconstruction in the condensed phase. PMID- 17275036 TI - Sequence and structural parameters enhancing adaptation of proteins to low temperatures. AB - A systematic analysis compared sequence and structural parameters distributions between 13 pairs of psychrophilic and mesophilic proteins for elucidating the cold adaptation parameters. The results of statistical test (t-test) revealed that helical content, tight turn content, disulfide bonds and hydrogen bonds do not show significant difference between psychrophilic and mesophilic proteins. However, it was demonstrated in this study that a larger proportion of open beta turn in psychrophilic proteins is an effective parameter in specific activity at low temperature. In addition, substitution of amino acids of charged and aliphatic groups with amino acids of tiny and small groups in protein chains, tight turns and alpha-helices in the direction from mesophilic to psychrophilic proteins is one of the mechanisms of low temperature adaptation. Such sequence and structural parameter differences would help to develop a strategy for designing cold-adapted proteins. PMID- 17275037 TI - Optimizing phylogenetic diversity under constraints. AB - Phylogenetic diversity (PD) is a measure of the extent to which different subsets of taxa span an evolutionary tree, and provides a quantitative tool for studying biodiversity conservation. Recently, it was shown that the problem of finding subsets of taxa of given size to maximize PD can be efficiently solved by a greedy algorithm. In this paper, we extend this earlier work, beginning with a more explicit description of the underlying combinatorial structure of the problem and its connection to greedoid theory. Next we show that an extension of the PD optimization problem to a phylogeographic setting is NP-hard, although a special case has a polynomial-time solution based on the greedy algorithm. We also show how the greedy algorithm can be used to solve some special cases of the PD optimization problem when the sets that are restricted to are ecologically 'viable'. Finally, we show that three measures related to PD fail to be optimized by a greedy algorithm. PMID- 17275038 TI - Floating plastic in the Kuroshio Current area, western North Pacific Ocean. PMID- 17275040 TI - The influence of time awake and circadian rhythm upon performance on a frontal lobe task. AB - Previous research has suggested a time-of-day effect for response inhibition on a task known to be dependent on frontal lobe function. We used a forced desynchronisation protocol to separate effects of circadian and sleep homeostat processes on a modified version of this task. Fourteen healthy young adults followed an experimental day length of 28 hr for 18 consecutive "days". There was a significant main effect of wake duration but no circadian component for inhibitory performance on this task. An interaction suggested that performance coinciding with the rising arm of the circadian cycle will vary dependent on the length of prior wakefulness. We suggest that the relationship between homeostatic sleep processes and circadian processes is complex and that their effects on cognitive processes are not easily separated by routine sleep-deprivation or time of-day studies. PMID- 17275039 TI - Mutagenicity of ultraviolet A radiation in the lacI transgene in Big Blue mouse embryonic fibroblasts. AB - Sunlight ultraviolet A (UVA) irradiation has been implicated in the etiology of human skin cancer. A genotoxic mode of action for UVA radiation has been suggested that involves photosensitization reactions giving rise to promutagenic DNA lesions. We investigated the mutagenicity of UVA in the lacI transgene in Big Blue mouse embryonic fibroblasts. UVA irradiation of these cells at a physiologically relevant dose of 18J/cm(2) caused a 2.8-fold increase in the lacI mutant frequency relative to control, i.e., 12.12+/-1.84 versus 4.39+/-1.99 x 10( 5) (mean+/-S.D.). DNA sequencing analysis showed that of 100 UVA-induced mutant plaques and 54 spontaneously arisen control plaques, 97 and 51, respectively, contained a minimum of one mutation along the lacI transgene. The vast majority of both induced- and spontaneous mutations were single base substitutions, although less frequently, there were also single and multiple base deletions and insertions, and tandem base substitutions. Detailed mutation spectrometry analysis revealed that G:C-->T:A transversions, the signature mutations of oxidative DNA damage, were significantly induced by UVA irradiation (P<0.003). The absolute frequency of this type of mutations was 7.4-fold increased consequent to UVA irradiation as compared to control (3.38 versus 0.454 x 10(-5); P<0.00001). These findings are in complete agreement with those previously observed in the cII transgene of the same model system, and reaffirm the notion that intracellular photosensitization reactions causing promutagenic oxidative DNA damage are involved in UVA genotoxicity. PMID- 17275041 TI - Visual and visuospatial short-term memory in mild cognitive impairment and Alzheimer disease: role of attention. AB - It has been proposed that visual recognition memory and certain attentional mechanisms are impaired early in Alzheimer disease (AD). Little is known about visuospatial recognition memory in AD. The crucial role of the hippocampus on spatial memory and its damage in AD suggest that visuospatial recognition memory may also be impaired early. The aim of the present study was to evaluate which modality, i.e. visual or visuospatial, is more implicated in the early memory impairment in AD. First, to determine onset of memory impairment, we compared the performances of patients with AD to those with amnestic mild cognitive impairment (MCI). Second, to determine the relative contribution of attentional impairment on the performance of MCI and AD patients, we tested the influence of a distractor in the interval between the memory image and recognition tests. Results showed that visuospatial short-term deficits appear earlier than visual short-term ones. In addition to mnemonic deficits, results showed attentional deficiency in both MCI and AD patients. Deficits of performances in visual modality seemed of attentional origin whereas those of visuospatial modality seemed of memory origin. The combination of attentional and mnemonic evaluation is likely to be a promising approach to finding predictive markers that distinguish MCI patients that convert to AD. PMID- 17275042 TI - Different patterns of famous people recognition disorders in patients with right and left anterior temporal lesions: a systematic review. AB - Selective disorders in recognition of familiar people have been described in patients with right and left anterior temporal lesions, but the exact nature of these cognitive impairments remains controversial. A clarification of this issue could have theoretical implications, because, according to Snowden et al. [Snowden, J. S., Thompson, J. C., & Neary, D. (2004). Knowledge of famous faces and names in semantic dementia. Brain, 127, 860-872], the pattern of impairment shown by patients with right and left anterior temporal atrophy is inconsistent with unitary, abstract, amodal models of semantic memory. This pattern could, on the contrary suggest a multimodal network, in which the right and left temporal lobes would mainly process and store visual and, respectively, verbal information. I tried to clarify this issue by systematically reviewing: (a) all published individual cases of patients showing a prevalent damage of the anterior parts of the right or left temporal lobes and a selective disorder of famous people recognition; (b) all group studies of patients with right or left temporal lobe epilepsy, which had investigated aspects of famous people recognition impairment. Results of these reviews consistently showed that different patterns of impaired recognition of familiar people can be observed in patients with right and left anterior temporal pathology. These patterns consist of a loss of familiarity feelings and of person specific information retrieval from face stimuli, when the right temporal lobe is damaged and of a prevalent impairment in finding their names when the anterior parts of the left temporal lobe are selectively damaged. PMID- 17275044 TI - Growth failure after recurrent fever in young guinea pigs. AB - Infection causes fever and suppression of appetite, a combination of effects which threatens normal growth in infected children. We have used an animal model to study the effects on growth of recurrent simulated Gram-positive bacterial infection. After weaning, 10 guinea pig pups underwent surgery under general anaesthesia for the implantation of temperature-sensitive radiotelemeters and thereafter were assigned to receive intramuscular injections of either 50 microg/kg muramyl dipeptide (MDP), or sterile saline. During a 30-day period corresponding to their rapid growth phase, the pups were given eight injections. MDP resulted in fevers of about 1.5 degrees C on each occasion, but no significant change in body temperature occurred after saline injections. Food intake was suppressed during each febrile episode such that 24-h intake was significantly lower on days of injections of MDP, compared to days between MDP injections in the same animals, and compared to that of animals injected with saline. The rate of weight gain of the MDP-injected guinea pigs was significantly lower than that of the control group and failed even to achieve a rate similar to the saline-injected group in their more adult-like growth phase. Plasma zinc concentration was significantly lower in MDP-compared to saline-injected animals sampled 8 days after the last injection. Our results show that recurrent fever during the growth phase of young guinea pigs results in irreversible growth failure, and that reduced food intake on days when the animals were febrile was at least partly responsible for this reduced rate of growth. PMID- 17275045 TI - Effects of the collagenolytic cell wall component of Fusobacterium necrophorum subsp. necrophorum on bovine hepatocytes. AB - The effects of the collagenolytic cell wall component (CCWC) of Fusobacterium necrophorum subsp. necrophorum on bovine hepatic cell and cytoskeletons were investigated. Scanning electron microscopy (SEM) demonstrated that CCWC damaged the cell surfaces, forming tiny holes on the cell membranes. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) profiles revealed that CCWC degraded bovine cytokeratin and vimentin and by indirect fluorescent antibody (IFA) method, it was shown that CCWC caused the deformation of hepatocellular vimentin. This suggested that CCWC contributes to bovine hepatic injury and it may be as important pathogenic factor in the development of bovine hepatic abscesses. PMID- 17275043 TI - The delayed effects of chronic unpredictable stress on anxiety measures. AB - Previous research has found that exposure to unpredictable stress can augment anxiety in humans and animals. The appearance of anxiety symptoms in humans frequently develop after stress exposure has terminated, but few rodent studies have systematically examined the delayed anxiogenic effects of unpredictable stress. Therefore, the current study investigated whether anxiety-like behaviors in rats would increase at several time intervals following exposure to chronic unpredictable stress (CUS). Unconditioned and conditioned response tasks were used to assess anxiety in male rats 1, 7 or 14 days following exposure to 10 days of a variety of stressors. Rats exposed to CUS showed increased burying behaviors and immobility during the defensive burying test, a conditioned anxiety test. The effects on burying behavior were apparent 7 and 14 days after the termination of the unpredictable stress procedure, but not when tested 1 day after CUS. Total time immobile in the defensive burying test also increased 14 days after termination of the last stressor. In contrast, there were no significant effects of CUS on behavioral measures in the unconditioned response tasks, the elevated plus-maze or light-dark box, at any time point following exposure to CUS. The current findings suggest that CUS may be a useful model of human conditioned anxiety that develops subsequent to chronic stress exposure. PMID- 17275046 TI - [Autotransplantation of an immature tooth]. AB - Autogenous tooth transplantation is indicated in young people treated by orthodontology, especially when they present with damaged first molars requiring extraction. This therapeutic alternative with a favourable prognosis is an elegant solution after a single tooth loss. PMID- 17275047 TI - [Congenital vascular leiomyosarcoma]. AB - INTRODUCTION: Vascular leiomyosarcoma is a conjunctive tumor which develops in the smooth muscle cells of vessel walls. Proximal vascular leiomyosarcoma involving the large vessels and peripheral vascular leiomyosarcoma which develops in the vascular pedicles of the limbs and subcutaneous vessels are distinguished. OBSERVATION: We report the case of a 6-year-old child who presented from birth a peripheral vascular leiomyosarcoma. The immunohistochimic study revealed tumor cell expression vimentin, SMA and desmine. In spite of wide surgical resection with associated chemotherapy, the child's clinical status deteriorated. DISCUSSION: Vascular leiomyosarcoma is a rare tumor occurring exceptionally in children. Prognosis depends on the presence of local recurrence and metastatic spread. PMID- 17275048 TI - [Nasal reconstruction with a three-staged forehead flap: assessment of 16 cases]. AB - INTRODUCTION: We report our experience in 16 patients with a three-staged forehead flap, described by Millard (1974) and Burguet (1992) for nasal reconstruction. We wanted to determine whether the three-stage procedure improves the quality of the final aesthetic result. MATERIALS AND METHODS: Sixteen patients underwent forehead flap nasal reconstruction between June 2002 and February 2005. Reconstruction was performed in three stages, a first stage for the transfer of the forehead flap on the nose, a second stage where the pediculized forehead flap was thinned (day 15) and a third stage for division of the pedicle (day 30). The quality of the final aesthetic result of nasal reconstruction was evaluated 6 months postoperatively, by the patient (patient's satisfaction with the nasal reconstruction [4 points]) and by the surgical team according to the thickness of the flap (3 points), integration of the scars (1 point), color of the flap (1 point) and the redefinition of the natural contour of the nose (1 point). A final 10-point score was used to assess the quality of the result: very good (score above 8), good (score from 7 to 8), average (score from 5 to 7) and poor (score less than 5). RESULTS: Sixteen nasal reconstructions were followed to completion. Outcome was considered very good in ten (62.5%), good in three (18.7%) and fair in three (18.7%). DISCUSSION: Use of the three stage procedure for forehead flap nasal reconstruction improved the contour of the flap by aggressive defatting of the still pediculized flap, and thus improving the final aesthetic result. Traditionally two stages are used for frontal flaps, with pedicle division at the first stage. This refinement must not be excessive because of the risk of necrosis, the frontal flap often requiring latter defatting. In the three-stage technique thinning is performed at the second stage on a vascularised, bipediculized flap, which makes it possible to obtain the desired refinement without excessive vascular risk. PMID- 17275049 TI - [Mandibular hemangiopericytoma, a malignant vascular tumor]. AB - INTRODUCTION: Hemangiopericytoma is a rare tumor, arising from pericytes, which are perivascular cells belonging to the capillar walls. OBSERVATION: A 41 year old man consulted for a mandibular tumor. The clinical and radiographic diagnosis was difficult. The biopsy performed in the operative room led to an embolization decided in emergency, and proved the definitive diagnosis. Despite the embolization, bleeding during surgical excision of the tumor compelled us to perform an external carotid artery ligature. The mandibular reconstruction was performed using a trapezium osteo-muscular flap. DISCUSSION: As reported in the literature, the radiographic diagnosis of hemangiopericytoma is difficult, the malignant potential is variable and the recommended treatment is surgical excision. PMID- 17275050 TI - [Mandibular fractures: epidemiology, therapeutic management, and complications in a series of 563 cases]. AB - INTRODUCTION: The Paris urban and suburban area (Ile-de-France) has the leading regional population in France. This population has specific characteristics. This study concerns mandibular fractures. MATERIAL AND METHOD: A retrospective epidemiologic, clinical, radiographical and therapeutic analysis is conducted with a series of 563 patients with mandibular fracture treated at the Pitie Salpetriere University Hospital, in Paris, from 1998 to 2000. RESULTS: Mandibular fracture was generally observed in young men, 40% of whom had poor oral hygiene. The brawls were the dominant etiology (57%) followed by road accidents (12%). The most frequent unifocal fractures were condylar fractures (32%) and angle fractures (32%). The most frequent bifocal mandibular fracture associated angle and symphysis fractures (32%). Osteosynthesis was performed for 73% of patients, including 30% with associated maxillary locking. Complications occurred in 4.8% of the studied cases. DISCUSSION: Despite the increase in traffic, the incidence of road injuries has declined. The first leading and progressing cause of mandibular fractures is brawls. Surgical treatment generally consists in fixation of the bone fracture. Maxillary locking is still associated in 33% of patients, but with a 50% shorter duration. Complications routinely arise because of poor bad oral hygiene. PMID- 17275052 TI - [Cancer of the floor of the mouth in a ninety-four year old female patient: a record and its justification]. AB - INTRODUCTION: Patient's age is known to have no influence on either treatment or prognosis of oral squamous cell carcinoma. OBSERVATION: A 94-year old female patient, with a squamous cell carcinoma of the floor of the mouth, stage pT1pN0cM0, was classically treated by surgical tumor resection, selective neck dissection and immediate surgical reconstruction with a vascularized radial flap. DISCUSSION: This clinical case, which could be a record taking into account the patient's advanced age, confirms that treatment decision of oral squamous cell carcinoma must not be influenced by age. Only some age-related comorbidities must be considered. PMID- 17275053 TI - Isolation and propagation of Trypanosoma brucei gambiense from sleeping sickness patients in south Sudan. AB - This study aimed at isolating Trypanosoma brucei gambiense from human African trypanosomiasis (HAT) patients from south Sudan. Fifty HAT patients identified during active screening surveys were recruited, most of whom (49/50) were in second-stage disease. Blood and cerebrospinal fluid samples collected from the patients were cryopreserved using Triladyl as the cryomedium. The samples were stored at -150 degrees C in liquid nitrogen vapour in a dry shipper. Eighteen patient stabilates could be propagated in immunosuppressed Mastomys natalensis and/or SCID mice. Parasitaemia was highest in SCID mice. Further subpassages in M. natalensis increased the virulence of the trypanosomes and all 18 isolates recovered from M. natalensis or SCID mice became infective to other immunosuppressed mouse breeds. A comparison of immunosuppressed M. natalensis and Swiss White, C57/BL and BALB/c mice demonstrated that all rodent breeds were susceptible after the second subpassage and developed a parasitaemia >10(6)/ml by Day 5 post infection. The highest parasitaemias were achieved in C57/BL and BALB/c mice. These results indicate that propagation of T. b. gambiense isolates after initial isolation in immunosuppressed M. natalensis or SCID mice can be done in a range of immunosuppressed rodents. PMID- 17275054 TI - The role of Forkhead-box Class O (FoxO) transcription factors in cancer: a target for the management of cancer. AB - Human Forkhead-Box Class O (FoxO) transcription factors are primarily regulated through the phosphoinositide-3-kinase (PI3k)-Akt pathway via phosphorylation and nuclear exclusion. Acetylation and ubiquitination represent another level of regulation for FoxO proteins and FoxO-regulated gene expression. FoxO factors can act as tumor suppressors; however, the loss of FoxO function leads to increased cellular survival and a predisposition to neoplasia, especially of epithelial cancers. Based on the critical role of FoxO signaling, this family of transcription factors appears to be a promising target for future drug discovery for epithelial cancers. This review describes mechanism of the regulation of FoxO proteins and their role in epithelial cancers. Based on the current knowledge and studies in the past decade, we suggest that the development of novel agents which specifically activate FoxO members could be useful in the prevention as well as treatment of cancer in general and epithelial cancers in particular. PMID- 17275056 TI - Molecular characterisation of hepatopancreatic parvovirus (PmergDNV) from Australian Penaeus merguiensis. AB - Hepatopancreatic parvovirus infection is associated with reduced growth rates of prawns during the juvenile stages and overt mortalities. Hepatopancreatic parvovirus was purified from Penaeus merguiensis from northern Queensland and a partial consensus sequence of 5.9 kb was obtained. Nucleotide comparisons revealed that the Australian isolate of HPV has a nucleotide similarity (87%) closer to HPVchin and the full sequence of HPV Penaeus monodon (PmDNV) (6321 bp) than to HPVsemi (83%). Three putative open reading frames were identified. The first open reading frame encoded a nonstructural protein (NS2) and shared an amino acid similarity of 86% with PmDNV. The second ORF overlapped the first open reading frame and shared 93% and 26% amino acid similarity with PmDNV and PstDNV, respectively, and encoded NS1. The third ORF encoded the viral structural protein and shared an amino acid similarity of 73% with the capsid protein of PmDNV and HPVchin. The phylogeny suggests that the Australian HPV isolate is closely related to the Korean HPVchin isolate than to the Indian HPVsemi and Thai PmDNV isolates. HPV strains may be following the phylogenetic relationship of penaeid prawn hosts rather than their geography. PMID- 17275055 TI - Lack of temporal structure in the short term HIV-1 evolution within asymptomatic naive patients. AB - HIV-1 evolution in the envelope gene (env) was analyzed in four asymptomatic antiretroviral therapy naive patients with typical and slow disease progression rates. In typical progressors, viral populations were monophyletic and two distinct evolutionary patterns were observed. In one patient, HIV-1 evolution displayed a strong temporal structure similar to the consistent pattern previously described. In the other, viral evolution displayed a lack of temporal structure with no increase in genetic heterogeneity and divergence over time. In slow progressors, several clades were observed in viral populations. However, analysis within the major sub-population revealed the same two evolutionary patterns described for typical progressors. Synonymous and non-synonymous substitution rate analyses indicated that positive selection was the major force driving HIV-1 evolution in viral populations with temporal structure, while evolution in viral populations with an atemporal structure was dominated by genetic drift and purifying selection. These results support the existence of distinct patterns of env evolution in untreated HIV-1-infected patients. PMID- 17275059 TI - Luminance texture increases perceived speed. AB - Previous psychophysical experiments have demonstrated that various factors can exert a considerable influence on the apparent velocity of visual stimuli. Here, we investigated the effects of superimposing static luminance texture on the apparent speed of a drifting grating. In Experiment 1, we demonstrate that superimposing static luminance texture on a drifting luminance modulated grating can produce an increase in perceived speed. This supports the hypothesis that texture changes perceived speed by providing landmarks to assess relative motion. In Experiment 2, we showed that contrary to static luminance texture, dynamic luminance texture did not increase perceived speed. This demonstrates that texture must provide reliable spatial landmarks in order to generate an increase in perceived speed. The results of Experiment 3 demonstrate that perceived speed depends on the size of the area covered by texture. This suggests that luminance texture and the motion stimulus interacted with each other over a limited spatial scale and that these local responses are then pooled to determine the speed of the motion stimulus. In Experiment 4, we showed that static texture contrast could produce a greater effect than motion stimulus contrast on perceived speed and that these effects could still be observed at brief presentation times. We discuss these findings in the context of models proposed to account for phenomena in the perception of speed. PMID- 17275057 TI - Structure and immunogenicity of alternative forms of the simian immunodeficiency virus gag protein expressed using Venezuelan equine encephalitis virus replicon particles. AB - Venezuelan equine encephalitis virus replicon particles (VRP) were engineered to express different forms of SIV Gag to compare expression in vitro, formation of intra- and extracellular structures and induction of humoral and cellular immunity in mice. The three forms examined were full-length myristylated SIV Gag (Gagmyr+), full-length Gag lacking the myristylation signal (Gagmyr-) or a truncated form of Gagmyr- comprising only the matrix and capsid domains (MA/CA). Comparison of VRP-infected primary mouse embryo fibroblasts, mouse L929 cells and primate Vero cells showed comparable expression levels for each protein, as well as extracellular virus-like particles (VRP-Gagmyr+) and distinctive cytoplasmic aggregates (VRP-Gagmyr-) with each cell type. VRP were used to immunize BALB/c mice, and immune responses were compared using an interferon (IFN)-gamma ELISPOT assay and a serum antibody ELISA. Although all three VRP generated similar levels of IFN-gamma-producing cells at 1 week post-boost, at 10 weeks post-boost the MA/CA-VRP-induced response was maintained at a significantly higher level relative to that induced by Gagmyr+-VRP. Antibody responses to MA/CA-VRP and Gagmyr+-VRP were not significantly different. PMID- 17275058 TI - The duration of the attentional blink in natural scenes depends on stimulus category. AB - Humans comprehend the "gist" of even a complex natural scene within a small fraction of a second. If, however, observers are asked to detect targets in a sequence of rapidly presented items, recognition of a target succeeding another target by about a third of a second is severely impaired, the "attentional blink" (AB) [Raymond, J. E., Shapiro, K. L., & Arnell, K. M. (1992). Temporary suppression of visual processing in an RSVP task: an attentional blink? Journal of Experimental Psychology. Human Perception and Performance, 18, 849-860]. Since most experiments on the AB use well controlled but artificial stimuli, the question arises whether the same phenomenon occurs for complex, natural stimuli, and if so, whether its specifics depend on stimulus category. Here we presented rapid sequences of complex stimuli (photographs of objects, scenes and faces) and asked observers to detect and remember items of a specific category (either faces, watches, or both). We found a consistent AB for both target categories but the duration of the AB depended on the target category. PMID- 17275060 TI - The influence of punctuation and word class on distributed processing in normal reading. AB - A series of multiple regression analyses was conducted on a corpus of eye movement data to examine whether the influence of properties of words n-1 and n+1 on the time spent fixating word n changes as a function of whether word n is associated with a punctuation mark (i.e., whether or not a punctuation mark separates word n from either word n-1 or word n+1). The results suggest that distributed processing is not significantly impaired. However, punctuation marks also carry word class information and word classes are not evenly distributed across positions relative to punctuation marks. Word class probability does modulate parafoveal-on-foveal effects. PMID- 17275061 TI - A neural model of 3D shape-from-texture: multiple-scale filtering, boundary grouping, and surface filling-in. AB - A neural model is presented of how cortical areas V1, V2, and V4 interact to convert a textured 2D image into a representation of curved 3D shape. Two basic problems are solved to achieve this: (1) Patterns of spatially discrete 2D texture elements are transformed into a spatially smooth surface representation of 3D shape. (2) Changes in the statistical properties of texture elements across space induce the perceived 3D shape of this surface representation. This is achieved in the model through multiple-scale filtering of a 2D image, followed by a cooperative-competitive grouping network that coherently binds texture elements into boundary webs at the appropriate depths using a scale-to-depth map and a subsequent depth competition stage. These boundary webs then gate filling-in of surface lightness signals in order to form a smooth 3D surface percept. The model quantitatively simulates challenging psychophysical data about perception of prolate ellipsoids [Todd, J., & Akerstrom, R. (1987). Perception of three dimensional form from patterns of optical texture. Journal of Experimental Psychology: Human Perception and Performance, 13(2), 242-255]. In particular, the model represents a high degree of 3D curvature for a certain class of images, all of whose texture elements have the same degree of optical compression, in accordance with percepts of human observers. Simulations of 3D percepts of an elliptical cylinder, a slanted plane, and a photo of a golf ball are also presented. PMID- 17275062 TI - Lack of spontaneous ocular neovascularization and attenuated laser-induced choroidal neovascularization in IGF-I overexpression transgenic mice. AB - Robust IGF-I overexpression induces ocular angiogenesis in mice. To investigate the effect of subtle IGF-I overexpression, we examined the ocular phenotype of IGF-II promoter-driven IGF-I transgenic mice. Despite 2.5-fold elevation of IGF-I mRNA in the retina and 29 and 52% increase of IGF-I protein in the retina and aqueous humor, respectively, no ocular abnormality was observed in these transgenics. This was correlated with unaltered VEGF mRNA levels in the transgenic retina. The transgene was also associated with an attenuated laser induced choroidal neovascularization. Differential expression levels and pattern of IGF-I gene may underlie the different retinal phenotypes in different transgenic lines. PMID- 17275063 TI - Separate first- and second-order processing is supported by spatial summation estimates at the fovea and eccentrically. AB - We estimated spatial summation areas for the detection of luminance-modulated (LM) and contrast-modulated (CM) blobs at the fovea, 2.5, 5 and 10 deg eccentrically. Gaussian profiles were added or multiplied to binary white noise to create LM and CM blob stimuli and these were used to psychophysically estimate detection thresholds and spatial summation areas. The results reveal significantly larger summation areas for detecting CM than LM blobs across eccentricity. These differences are comparable to receptive field size estimates made in V1 and V2. They support the notion that separate spatial processing occurs for the detection of LM and CM stimuli. PMID- 17275064 TI - Homogeneous iron-catalyzed photochemical degradation of muconic acid in water. AB - Iron photochemical oxidation has been used to remove muconic acid from water. Two different light systems were used: black lamps and solar irradiation. The effect of iron concentration, intensity of incident radiation, pH and presence of oxalic acid was investigated. The first two variables yield positive effects on the removal rate of muconic acid while higher efficiency was achieved at pH 3. Oxalic acid enhances the oxidation rate because of the formation of photoactive ferrioxalate ion. Stoichiometric results indicated formation of two hydroxyl radicals to degrade 1 mol of muconic acid. At similar experimental conditions, initial oxidation rates of muconic acid were higher when solar light was used to irradiate the aqueous solutions, although in this case, the oxidation process is stopped because of the consumption of photoactive species. PMID- 17275065 TI - The application of a recently isolated strain of Bacteroides (GB-124) to identify human sources of faecal pollution in a temperate river catchment. AB - Recent work has suggested that bacteriophages infecting Bacteroides are a potential tool for faecal source tracking, but that different host strains may be needed for different geographic areas. This study used a recently identified strain of Bacteroides (GB-124) to detect human sources of faecal pollution in a river catchment in southeast England (UK). A total of 306 river water, municipal wastewater and animal samples were obtained over a 16-month period. Bacteriophages capable of infecting GB-124 were present in all municipal wastewaters but were not detected in faecal samples from animals, and were detected at significantly lower levels (P< 0.001) in river waters directly downstream of a dairy farm. This last observation was despite the presence of high levels of faecal indicator bacteria at this site. The study suggests that GB 124 appears to be specific to human faeces. As such it may represent an effective and low-cost method of faecal source identification. PMID- 17275066 TI - Solids accumulation in six full-scale subsurface flow constructed wetlands. AB - In this study, we evaluated the amount of accumulated solids in six different horizontal subsurface flow constructed wetlands (SSF CWs). We also investigated the relationship between accumulated solids and, on one hand, the wastewater quality and load and, on the other hand, the hydraulic conductivity of the granular medium. Aerobic and anaerobic biodegradability tests were also conducted on the accumulated organic matter. Experiments were carried out on full scale wastewater treatment systems consisting of SSF CWs with stabilisation ponds, which are used for the sanitation of small towns in north-eastern Spain. There were more accumulated solids near the inlet of the SSF CWs (3-57 kg dry matter (DM)/m2) than near the outlet (2-12 kgm DM/m2). Annual solids accumulation rates ranged from 0.7 to 14.3 kg DM/m2 year, and a positive relationship was observed between accumulation rates and loading rates. Most of the accumulated solids had a low level of organic matter (<20%). The results of the aerobic and anaerobic tests indicated that the accumulated organic matter was very recalcitrant and difficult to biodegrade. The hydraulic conductivity values were significantly lower near the inlet zone (0-4 m/d) than in the outlet zone (12-200 m/d). Although hydraulic conductivity tended to decrease with increasing solids accumulation, the relationship was not direct. One major conclusion of this study is that the improvement of primary treatment is necessary to avoid rapid clogging of the granular media due to solids accumulation. PMID- 17275067 TI - Stereochemistry of reduction in digeranylgeranylglycerophospholipid reductase involved in the biosynthesis of archaeal membrane lipids from Thermoplasma acidophilum. AB - The basic core structure of archaeal membrane lipids is 2,3-di-O-phytanylglyceryl phosphate, which is formed by reduction of 2,3-di-O-geranylgeranylglyceryl phosphate. This reaction is the final committed step in the biosynthesis of archaeal membrane lipids and is catalyzed by digeranylgeranylglycerophospholipid reductase (DGGGPL reductase). The putative DGGGPL reductase gene (Ta0516m) of Thermoplasma acidophilum was cloned and expressed. The purified recombinant enzyme appeared to catalyze the formation of 2,3-di-O-phytanylglyceryl phosphate from 2,3-di-O-geranylgeranylglyceryl phosphate, which confirmed that the Ta0516m gene of T. acidophilum encodes DGGGPL reductase. The stereospecificity in reduction of 2,3-di-O-phytylglyceryl phosphate by the recombinant reductase appeared to take place through addition of hydrogen in a syn manner by analyzing the enzyme reaction product by NMR spectroscopy. PMID- 17275068 TI - Agriculture and groundwater nitrate contamination in the Seine basin. The STICS MODCOU modelling chain. AB - A software package is presented here to predict the fate of nitrogen fertilizers and the transport of nitrate from the rooting zone of agricultural areas to surface water and groundwater in the Seine basin, taking into account the long residence times of water and nitrate in the unsaturated and aquifer systems. Information on pedological characteristics, land use and farming practices is used to determine the spatial units to be considered. These data are converted into input data for the crop model STICS which simulates the water and nitrogen balances in the soil-plant system with a daily time-step. A spatial application of STICS has been derived at the catchment scale which computes the water and nitrate fluxes at the bottom of the rooting zone. These fluxes are integrated into a surface and groundwater coupled model MODCOU which calculates the daily water balance in the hydrological system, the flow in the rivers and the piezometric variations in the aquifers, using standard climatic data (rainfall, PET). The transport of nitrate and the evolution of nitrate contamination in groundwater and to rivers is computed by the model NEWSAM. This modelling chain is a valuable tool to predict the evolution of crop productivity and nitrate contamination according to various scenarios modifying farming practices and/or climatic changes. Data for the period 1970-2000 are used to simulate the past evolution of nitrogen contamination. The method has been validated using available data bases of nitrate concentrations in the three main aquifers of the Paris basin (Oligocene, Eocene and chalk). The approach has then been used to predict the future evolution of nitrogen contamination up to 2015. A statistical approach allowed estimating the probability of transgression of different concentration thresholds in various areas in the basin. The model is also used to evaluate the cost of the damage resulting of the treatment of drinking water at the scale of a groundwater management unit in the Seine river basin. PMID- 17275069 TI - Evaluation and performance characteristics of the automated coagulation analyzer ACL TOP. AB - INTRODUCTION: The ACL TOP is a fully-automated random-access multiparameter coagulation analyzer equipped with a photo-optical clot-detection unit. It is designed to perform coagulation, chromogenic and immunologic assays with continuous loading capabilities for samples, reagents and disposables. MATERIALS AND METHODS: The instrument was evaluated in a coagulation laboratory of a university hospital with respect to its technical features in the determination of routine coagulation (prothrombin time, activated partial thromboplastin time, fibrinogen and single coagulation factor levels), chromogenic (anti-activated factor X, antithrombin and protein C activities) and immunologic assays (free protein S and von Willebrand factor antigen concentrations). RESULTS: Using fresh and lyophilized plasma samples, the intra-assay and inter-assay coefficients of variation were below 5% for most of the parameters both in the normal and in the pathological ranges. For clotting assays performed at 671 nm, no significant interference could be demonstrated with hemolytic, icteric and lipemic samples as demonstrated by results similar to those obtained using a mechanical clot detection-based analyzer (STAR). No sample carryover was detected in measuring alternatively heparinized (1.0 IU/mL unfractionated heparin) and normal plasma samples. The results of the different coagulation, chromogenic and immunologic assays obtained on the ACL TOP were well correlated with those obtained on the STAR analyzer with the correlation coefficient (r) in the range from 0.876 to 0.990. CONCLUSIONS: Our results demonstrated that using the ACL TOP analyzer, routine hemostasis testing can be performed with satisfactory precision and the same applied to more specialized and specific tests such as single factor activity or antigen concentration. PMID- 17275070 TI - Survival analysis of 130 patients with papillary renal cell carcinoma: prognostic utility of type 1 and type 2 subclassification. AB - OBJECTIVES: To evaluate the prognostic significance of subtyping papillary renal cell carcinoma (PRCC) into type 1 and type 2 tumors. METHODS: From 1995 to 2004, 1358 patients underwent surgery for renal cell carcinoma, of whom 130 had PRCC alone on the specimen. The tumor characteristics, including their subtype, were analyzed; small basophilic cells and large eosinophilic cells were defined type 1 and type 2 tumors, respectively. Survival analyses were performed retrospectively. RESULTS: Of the 130 patients (110 men and 20 women, mean age 60.6 +/- 15.3 years) with PRCC, 102 underwent radical nephrectomy (78.4%) and 28 underwent partial nephrectomy (21.6%). The median tumor size was 4.5 cm (range 0.5 to 21). The comparison of the 68 (52.3%) type 1 PRCCs and 62 (47.7%) type 2 PRCCs revealed that type 2 tumors were associated with a greater stage and grade and microvascular invasion significantly (P <0.001) more often. The median follow up was 48 months (range 2 to 111). Of the 130 patients, 22 died of cancer specific causes, 5 (7%) with type 1 and 17 (27%) with type 2 tumors (P = 0.002). The overall and disease-free survival rate was 89% and 92% in type 1 tumors and 55% and 44% in type 2 tumors, respectively. Univariate analysis identified tumor type, stage (P <0.001), grade (P <0.001), microvascular invasion (P <0.001), an absence of foam cells (P <0.001), the presence of sarcomatoid cells (P = 0.001), and tumor necrosis (P = 0.007) as prognostic factors. Multivariate analysis retained tumor type (P = 0.034) and TNM stage (P <0.001). CONCLUSIONS: The results of our study have shown that histologic subtyping of PRCC allows for the identification of an independent prognostic factor. PMID- 17275071 TI - Postoperative inguinal hernia after radical prostatectomy for prostate cancer. AB - OBJECTIVES: To determine the incidence of inguinal hernia after radical prostatectomy and compare it with the incidence in patients with prostate cancer treated with radiotherapy. We also analyzed the effect of potential risk factors for inguinal hernia after radical prostatectomy. METHODS: We investigated the medical records of 53, 43, and 74 men who underwent open radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (LRP), or radiotherapy with or without laparoscopic pelvic lymph node dissection, respectively, and evaluated the respective incidence of inguinal hernia after these therapies. The risk factors were analyzed using a Cox proportional hazards model. RESULTS: The incidence of inguinal hernia was 17% (9 of 53), 14.0% (6 of 43), and 1.4% (1 of 74) in open RRP, LRP, and radiotherapy groups, respectively. Multivariate Cox proportional hazards analysis demonstrated that open RRP and LRP were significant risk factors for the development of inguinal hernia. CONCLUSIONS: Urologists should be aware that inguinal hernia is an important postoperative complication of open RRP. More interestingly, even LRP could promote the development of postoperative inguinal hernia. PMID- 17275072 TI - Routine pelvic drainage not required after open or robotic radical prostatectomy. AB - OBJECTIVES: To determine whether radical prostatectomy requires urinary drainage. METHODS: All patients with clinically localized prostate cancer had complete clinical and pathologic information recorded prospectively in a database. The criteria for omission of pelvic drainage were successful bladder neck preservation; urethrovesical anastomosis performed using 6 interrupted sutures in open cases or 12 continuous sutures in robotic cases; and a watertight urethrovesical anastomosis on irrigation. Most patients were discharged on the first or second postoperative day. The catheters were removed routinely on postoperative day 9. RESULTS: A pelvic drain was not placed in 78% of 325 consecutive patients. A drain was omitted in 73% of 225 open cases and 90% of 100 robotic cases. The recovery of continence and the complication rates were similar between the two groups with and without pelvic drainage. Complications occurred in 11% of the group with pelvic drainage and 6% in the group without pelvic drainage. In the past 2 years, 17 of 126 patients required pelvic drainage. The frequency of complications in robotic versus open procedures was similar (chi square test, P >0.05). CONCLUSIONS: Pelvic drainage may be omitted after radical prostatectomy when the urethrovesical anastomosis is performed well. Drainage omission could contribute to shortened hospital stays and reduced costs, without added complications. These benefits can be extended safely to patients undergoing open or robotic radical prostatectomy. PMID- 17275073 TI - Efficacy and safety of en bloc ligation of renal hilum during laparoscopic nephrectomy. AB - OBJECTIVES: To evaluate the feasibility, efficacy, and safety of en bloc ligation of the renal hilum with titanium vascular staplers during laparoscopic nephrectomy. En bloc ligation of the renal hilum has historically been associated with the very rare complication of arteriovenous fistula (AVF) formation, primarily in inflammatory renal pathologic features. Currently, no evidence exists of AVF development in human nephrectomies after ligating the hilum en bloc with titanium staplers. METHODS: A total of 161 consecutive patients underwent planned laparoscopic radical nephrectomy or nephroureterectomy. A retrospective review was performed to evaluate the operative variables, including the method of hilar ligation, estimated blood loss, and final pathologic findings. The additional postoperative outcomes of diastolic blood pressure, heart rate, and other cardiovascular sequelae were evaluated. RESULTS: Of the 161 patients, 90 underwent en bloc hilar ligation and 71 underwent individual hilar vessel ligation with the stapler. The blood loss and open conversion rate trended lower in the en bloc group. Postoperatively, no differences were found in blood pressure or heart rate between the two groups, and no instances of bruits or other clinical evidence of AVF were found after mean follow-up of 34 months. CONCLUSIONS: This series found no evidence of AVF or other adverse clinical events in patients undergoing en bloc ligation of the renal hilum and laparoscopic nephrectomy. En bloc ligation may provide for more secure, expeditious control of the hilum without an increased operative time or the added potential of vascular injury that can be associated with the individual dissection of the vessels. PMID- 17275074 TI - Prevalence of metabolic syndrome and its association with erectile dysfunction among urologic patients: metabolic backgrounds of erectile dysfunction. AB - OBJECTIVES: To identify the prevalence of metabolic syndrome (MS) and its association with erectile dysfunction (ED) among urologic patients. METHODS: The study population consisted of 393 male patients aged 40 to 70 years, who were admitted to the urology clinics of four different institutions from February to March 2005. The waist circumference (WC) and triglyceride (TG) and high-density lipoprotein (HDL) cholesterol levels were measured. Patients were divided into two groups: group 1 consisted of patients with a WC greater than 102 cm, and group 2 consisted of patients with a WC of less than 102 cm. The erectile status of the two groups was compared. RESULTS: Of the 393 patients, 157 (39.9%) had MS. Of the 393 patients, 124 with MS (79%) and 146 without MS (61.9%) had ED. The presence of MS was significantly associated with ED (P <0.001). In the presence of an increased WC with normal serum HDL and TG levels, the relative risk of ED was 1.94. If the patient with an increased WC had a pathologic level of HDL or TG, the relative risk of ED increased up to 2.97-fold. The relative risk of ED in the presence of an increased WC, together with pathologic levels of HDL and TG, was 3.38. CONCLUSIONS: In our study, MS was strongly associated with ED. Fasting blood glucose levels, hypertension, and WC are the most significant risk factors predicting the risk of ED. A more pronounced increase in ED risk in the presence of abdominal obesity, together with altered TG and HDL cholesterol levels, may indicate a special metabolic background of ED regarding lipid metabolism. PMID- 17275075 TI - Assessing urgency in interstitial cystitis/painful bladder syndrome. AB - OBJECTIVES: Interstitial cystitis/painful bladder syndrome (IC/PBS) at present is a symptom-based diagnosis. The Interstitial Cystitis Symptom Index (ICSI), also known as the O'Leary-Sant Symptom Index, is a widely used scale that assesses the four cardinal symptoms of IC/PBS (ie, bladder pain, urgency, frequency, and nocturia), by asking how often each is experienced. In an ongoing case-control study of recent-onset IC/PBS, we compared the ICSI with a series of questions that addressed the severity of these symptoms. METHODS: Recruiting nationally, we enrolled women with IC/PBS symptoms of 12 months' duration or less. We assessed the severity of pain, frequency, and urgency using Likert and categorical scales, and how often these symptoms were experienced using the ICSI. We compared these scales by frequency distributions and interscale correlations. RESULTS: In 138 women with recent-onset IC/PBS, the scores for frequency were correlated and, for pain, appeared to be complementary. However, for urgency, the ICSI question of "the strong need to urinate with little or no warning" consistently yielded lower scores than the severity question of "the compelling urge to urinate that is difficult to postpone." Some patients denied urgency to the ICSI question yet reported intense urgency to the severity question. CONCLUSIONS: Compared with the severity question, the ICSI underestimated the prevalence and degree of urgency. This observation is consistent with the views of others that sudden urgency does not define the sensation experienced by many patients with IC/PBS. Clarifying this symptom description may assist in developing a usable case definition for IC/PBS. PMID- 17275076 TI - Absence of Bcl-xL down-regulation in response to cisplatin is associated with chemoresistance in ovarian carcinoma cells. AB - OBJECTIVE: Recurrence and subsequent acquired chemoresistance to platinum-based treatments constitute major hurdles to ovarian carcinoma therapy. Our objective was to examine the involvement of Bcl-xL anti-apoptotic protein in resistance to cisplatin. METHODS: We described the effect of cisplatin on cell cycle and apoptosis induction in sensitive (IGROV1 and OAW42) and resistant (IGROV1-R10 and SKOV3) ovarian carcinoma cell lines. We correlated it with Bcl-xL mRNA and protein expression after exposure to cisplatin. We then used bcl-xS gene transfer to impede Bcl-xL activity. RESULTS: Our study showed that Bcl-xL basal expression was high in both sensitive and resistant cell lines, as well as in all the studied ovarian tumor samples. Thus, Bcl-xL basal expression could not allow to predict sensitivity. Wondering whether variation of Bcl-xL level in response to cisplatin could be a better determinant of sensitivity, we investigated the expression of this protein in the cell lines after treatment. Cisplatin-induced down-regulation of Bcl-xL was strictly associated with apoptosis and absence of recurrence in vitro. Conversely, the maintenance of Bcl-xL expression in response to cisplatin appeared as a sine qua non condition to escape to treatment. To try to sensitize SKOV3 cells by impeding anti-apoptotic activity of Bcl-xL, we transfected bcl-xS gene in these cells. Bcl-xS exogenous expression was only slightly cytotoxic on its own, but highly sensitized SKOV3 resistant cells to cisplatin-induced apoptosis, and delayed recurrence. CONCLUSION: This work thus provides one more argument to put Bcl-xL forward as a pertinent target of inhibition to overcome chemoresistance of epithelial ovarian carcinoma. PMID- 17275077 TI - Laparoscopy versus laparotomy for the surgical management of apparent early stage ovarian cancer. AB - OBJECTIVE: To compare the results of laparoscopic staging of apparent early ovarian cancer (EOC) with those obtained with comprehensive surgical staging via laparotomy. METHODS: Consecutive patients undergoing comprehensive laparoscopic staging for presumed EOC (LPS group; N=15) were compared with historical controls selected from consecutive women who have had conventional staging with open surgery (LPT group; N=19). RESULTS: No difference was found in demographics and preoperative variables between the two groups. There were no significant differences between the two groups with regard to median number of lymph nodes and likelihood of identifying metastatic disease. No conversion to laparotomy and no intraoperative complication occurred in the LPS group. Operative time was significantly longer in the LPS group when compared with the LPT group (377+/-47 vs. 272+/-81 min, P=0.002). One patient in the LPS group had a retroperitoneal haematoma recognized in the postoperative period, and this required laparotomy and ligature of the hypogastric arteries to achieve haemostasis. Minor postoperative complications occurred in 1 (6.7%) patient in the LPS group and in 8 (42.1%) patients in the LPT group (P=0.047). Hospital stay was significantly shorter in the LPS group [3 (2-12) vs. 7 (4-14) days, P=0.001]. Median (range) follow-up time was 16 (4-33) and 60 (32-108) months in the LPS and LPT group, respectively. Eleven (73.3%) patients in the LPS group and 13 (68.4%) in the LPT group received adjuvant treatment. There were no recurrences in the LPS group whereas 4 (7.1%) recurrences occurred in the LPT group. Overall survival was 100% in both groups. CONCLUSION: Our results suggest that laparoscopic comprehensive surgical staging of EOC is as safe and adequate as the standard surgical staging performed via laparotomy. PMID- 17275078 TI - Involvement of the alpha4beta2 nicotinic receptor subtype in nicotine-induced attenuation of delta9-THC cerebellar ataxia: role of cerebellar nitric oxide. AB - We have recently reported that mediation of intracerebellar nicotine-induced attenuation of cerebellar delta9-THC ataxia was via the alpha4beta2 nAChR. The present study was meant to investigate the role of cerebellar nitric oxide (NO) guanylyl cyclase (GC) signaling in the alpha4beta2-mediated attenuation in CD-1 male mice. Drugs were given via intracerebellar microinfusion using stereotaxically implanted guide cannulas, with ataxia evaluated by Rotorod. Intracerebellar microinfusion of SNP (sodium nitroprusside, NO donor; 15, 30, 60 pg) and SMT (S-methylisothiourea, inhibitor of inducible NO synthase; 70, 140, 280 fg) significantly enhanced and reduced, respectively, intracerebellar RJR 2403 (selective alpha4beta2 agonist)-induced attenuation of delta9-THC ataxia dose-dependently. Intracerebellar isoliquiritigenin (GC-activator; 1, 2, 4 pg) and ODQ (1H[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, GC inhibitor; 200, 400, 800 fg), significantly enhanced and reduced, respectively, intracerebellar RJR-2403 induced attenuation of delta9-THC ataxia dose-dependently. Further support for the role of NO was evidenced via increases in cerebellar NO(x) (nitrate+nitrite) levels following microinfusion of nicotine or RJR-2403 as compared to control, whereas delta9-THC significantly decreased NO(x) levels. "Nicotine/RJR 2403+delta9-THC" treated mice had cerebellar NO(x) levels significantly increased as compared to mice infused with delta9-THC alone. Results of the present investigation support the role of cerebellar NO-GC signaling in alpha4beta2 nAChR subtype-mediated attenuation of delta9-THC ataxia. PMID- 17275079 TI - Lordosis facilitation by LHRH, PGE2 or db-cAMP requires activation of the kinase A signaling pathway in estrogen primed rats. AB - Dose-response curves for lordosis and proceptive behaviors were obtained for luteinizing hormone releasing hormone (LHRH), prostaglandin E2 (PGE2) and dibutyryl cyclic AMP (db-cAMP), by infusing them in the right lateral ventricle (i.c.v.) of ovariectomized (OVX) estradiol benzoate (E2B; 2 microg) treated rats. Two dose levels, one producing the maximal effect and the other one producing a submaximal response (approximately ED50) were selected for testing the capacity of Rp-cAMPS, a kinase A blocker, to modify the behavioral response to the three compounds. I.c.v. injections of Rp-cAMPS, significantly depressed both lordosis and proceptive responses induced by LHRH, PGE2 and db-cAMP. The results show that these agents use the cAMP-kinase A signaling pathway to elicit their stimulating effect on estrous behavior in the rat. PMID- 17275081 TI - Basal and GnRH-induced secretion of FSH and LH in anestrous versus ovariectomized bitches. AB - The basal and gonadotropin releasing hormone (GnRH)-induced plasma concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were studied in four anestrous and four ovariectomized (OVX) bitches. Blood samples were obtained via jugular venipuncture 40min before and 0, 10, 20, 30, 60, 90, and 120min after the i.v. administration of synthetic GnRH in a dose of 10microg/kg body weight. The basal plasma FSH and LH concentrations were significantly higher in the OVX bitches than in the anestrous bitches. In the anestrous bitches, the plasma FSH concentration was significantly higher than the pretreatment level at 10, 20, and 30min, whereas the plasma LH concentration was significantly elevated at 10 and 20min. The maximal GnRH-induced plasma FSH concentration in the anestrous bitches did not surpass the lowest plasma FSH concentration in the OVX bitches, whereas the GnRH-induced plasma LH concentrations in the anestrous bitches overlapped with the basal plasma LH concentrations in the OVX bitches. In the OVX bitches, GnRH administration did not induce a significant change in the plasma FSH concentration, whereas the plasma LH concentration increased significantly at 10 and 20min. In conclusion, the results of the present study indicate that in anestrous bitches GnRH challenge results in increased plasma levels of both FSH and LH, whereas in the OVX bitches, in which the basal plasma FSH and LH concentrations are higher, only a rise in the plasma LH concentration is present after GnRH stimulation. The results also suggest that a test to measure plasma concentration of FSH in single samples appears to have potential in verification of neuter status in bitches. PMID- 17275080 TI - GABA enhancement of maternal defense in mice: possible neural correlates. AB - Previous studies have shown that low doses of GABA(A) receptor agonists facilitate maternal defense of offspring (maternal aggression), without significantly affecting other maternal behaviors. In addition, it has been demonstrated that endogenous changes in GABAergic neurotransmission occur in association with lactation. This study investigated the effects of GABA(A) receptor agonist, chlordiazepoxide (CDP), a benzodiazepine (BDZ), on maternal behaviors including aggression, and identified brain regions with altered activity in association with treatment. Another aim of the study was to determine whether CDP injections could prevent decreases in maternal aggression that occur with pup separation. Intraperitoneal injections of 1 mg/kg of CDP significantly increased maternal defense without affecting other maternal behaviors, although a trend towards elevated nursing was noted. CDP significantly reduced c-Fos in lateral septum (LS) and caudal periaqueductal gray (cPAG) in behaviorally experienced mice relative to vehicle-injected controls. In behaviorally-naive subjects, CDP also decreased c-Fos in LS, but in cPAG this decrease was just above significance (p=0.051). CDP was not sufficient to "rescue" maternal aggression when pup stimulus was removed. Overall, these studies provide further insights into the role for GABA in maternal behaviors, including aggression, and how and where BDZs may act to modulate behavior. PMID- 17275082 TI - Systematic study of osteoblast and fibroblast response to roughness by means of surface-morphology gradients. AB - The surface roughness of a medical implant is of great importance since the surface is in direct contact with the host tissue (e.g. bone, fibrous tissue). The response of cells to roughness is different depending on the cell type. However, the influence of roughness on cell behavior has only rarely been systematically studied. We have developed a surface-modification process to produce roughness gradients that cover a wide range of roughness values on one substratum. Such gradients allow for systematic investigations of roughness on cell behavior. Gradients were fabricated using a two-step roughening and smoothening process, involving sandblasting and a subsequent chemical polishing step. In order to produce a set of identical surfaces we applied a replica technique. Cell experiments were carried out with rat calvarial osteoblasts (RCO) and human gingival fibroblasts (HGF). RCOs showed a significantly increased proliferation rate with increasing surface roughness. The footprint of osteoblasts varied in size at different positions on the gradient, remaining small on the rough end of the gradient and increasing considerably as the roughness decreased. HGF showed the opposite proliferation behavior, proliferation decreasing with increasing roughness. The fibroblast morphology was found to be similar to that seen for osteoblasts. PMID- 17275083 TI - Electrospun aliphatic polycarbonates as tailored tissue scaffold materials. AB - Two different aliphatic polycarbonates were synthesised from CO(2) and the respective epoxides. Poly(propyl carbonate) (PPC) was prepared by heterogeneous catalysis with zinc glutarate. Poly(cyclohexyl carbonate) (PCHC) was prepared via living copolymerisation homogeneously catalysed by a 3-amino-2-cyanoimidoacrylate zinc acetate complex and subjected to electrospinning. The obtained nanofibres had a well-defined morphology free of beads along the fibres and with slightly porous structures on their surface. Subsequently, low-power deep UV irradiations, previously applied for photochemical surface modifications of two-dimensional and three-dimensional scaffolds from biostable polymers, were performed. Here, an effect on surface and bulk properties of PPC nanofibres was observed. Surface modifications of both polymers affected plasma protein adsorption. Photochemical bulk modifications observed for the first time on PPC nanofibres are indicating the possibility of spatial control of biodegradation rates, hence allow for control of the progression of host/implant interactions in vivo. In particular PPC was used for cell culture of L929 fibroblasts and primary rat hepatocytes. Even delicate primary cells showed good adhesion to the scaffolds and high viability. PMID- 17275084 TI - The xenobiotic transporter ABCG2 plays a novel role in differentiation of trophoblast-like BeWo cells. AB - Trophoblast cells undergo loss of plasma membrane lipid asymmetry during cell fusion without further progression to terminal phases of apoptosis. The nature of the anti-apoptotic mechanisms providing cell survival during this process is unknown. Using a BeWo cell model, we explored the role of the xenobiotic/lipid transporter ABCG2 in promoting cell survival during forskolin-induced differentiation. Suppression of ABCG2 expression by siRNA led to a marked increase in phosphatidylserine externalisation followed by accumulation of ceramides and increased apoptosis. Expression of markers of syncytial formation (beta-hCG and HERV-W) was decreased by ABCG2 silencing, although fusion was unaffected. These findings suggest that ABCG2 protects cells during the period of transient membrane instability associated with cell differentiation and fusion, highlighting a novel, previously unrecognised role of ABCG2 as a survival factor during the formation of the placental syncytium. PMID- 17275085 TI - Optimization of technical conditions for the transformation of Pediococcus acidilactici P60 by electroporation. AB - Previously reported techniques for the electrotransfer of foreign DNA into pediococci yield only a small number of transformants/mug DNA, especially when using undomesticated strains. This study reports an improved protocol for the electrotransformation of pediococci, based on trials using Pediococcus acidilactici P60 and the plasmid pRS4C1. The improved protocol yields from 2 to 3 log units more transformants than the previously reported methods, with up to (9.1+/-1.3)x10(4) transformants/mug of foreign DNA under the best conditions identified. The most important modifications proposed are an increase in electric field strength during electroporation (from 12.5 to 20kV/cm) and a reduction in lysozyme concentration during the preparation of electrocompetent cells (from 4000 to 2000U/ml): together, these two modifications greatly improve transformant yield. In addition, increasing cell culture time (from OD(600nm)=0.6 to OD(600nm)=1.0-1.2) and increasing dl-threonine concentration in the growth medium (from 20 to 40mM) also contribute to improved electrotransformation efficiency. PMID- 17275086 TI - New advances in plant growth-promoting rhizobacteria for bioremediation. AB - Plant growth-promoting rhizobacteria (PGPR) are bacteria capable of promoting plant growth by colonizing the plant root. For a long period PGPR were mainly used for assisting plants to uptake nutrients from the environment or preventing plant diseases. Phytoremediation is a new and promising approach to remove contaminants in the environment. But using plants alone for remediation confronts many limitations. Recently, the application of PGPR has been extended to remediate contaminated soils in association with plants. Of all the present contaminants, the profound impacts of organic and heavy metal pollutants have attracted world wide attention. Here we review the progress of PGPR for remediation of soils contaminated with these two sources. PMID- 17275087 TI - Soil erosion and its impacts on water treatment in the northeastern provinces of Thailand. AB - The economy of Northeast Thailand is mainly based on agriculture. The transformation of forestlands to agricultural areas and the encroachment of riverbanks within the Phong watershed have caused severe soil erosion. Strong storms in rainy season exacerbate the problem of soil erosion. Difficulty in getting water drives people in the upstream region to live on riverbanks. Soil erosion affects water utility by increasing the turbidity in the Phong River and also by decreasing the water storage capacity of small reservoirs for the upstream residents, as well as that of the Ubolratana Dam. The rate of siltation in the Ubolratana Dam was estimated to be 1.5 million tons/year during 1965-1990. The main source of water supply is surface water in the Phong watershed, and fluctuating turbidity makes water treatment difficult. The maximum turbidity in the upstream Phong River exceeds 5000 NTU, whereas it is reduced to be about 300 NTU at the intake point of Khon Kaen Municipal Water Treatment Plant because the Ubolratana Dam works as a huge clarifier. Khon Kaen Municipal Waterworks has a daily water supply of 72,960 m3/day. The average amounts of alum used in the wet (May-October) and dry (November-April) periods are 42.33 g/m3 and 28.46 g/m3, respectively. The average costs of the amounts of alum used are 0.213 and 0.143 Bahts/m3 during the wet and dry periods, respectively. Fluctuation of turbidity in raw water makes it difficult to adjust alum dose, resulting in treated water quality unstable, and handling of sludge disposal difficult. PMID- 17275088 TI - Off-rate and concentration diversity in multidonor-derived dimers of immunoglobulin G. AB - IgG-dimers in multidonor-derived preparations of IgG antibodies represent not only agents of therapeutic potential, but also molecules of basic immunological interest since their composition mirrors the currently unknown range of clonal concentrations and affinities. To analyze this fundamental type of diversity, a computational model is developed in agreement with a density functional theory and used to simulate the dissociation kinetics of dimers separated from a 5000 donor-derived IgG preparation (protein concentration: 0.74 mg/mL) via superimposition of 8100 arbitrary combinations of off-rates and initial concentrations. The Greedy algorithm-like procedure described requires iterative and consecutive changes of 8 from a total of 11 fitting parameters and allows to approximate the probability density distributions of either quantities within defined limits (apparent off-rates: approximately 4 x 10(-4) to 9 x 10(-17)s(-1); concentrations: approximately 3 x 10(-20) to 1 x 10(-11)M) by lognormal distributions of log-log(10)-type, each of them adapted with four particular parameters, as well as the number of different dimer populations ( approximately 2 x 10(13)). Moreover, reasonably dimensioned equilibrium constants involved in monovalent and bivalent random IgG dimerization are estimated by using a mean on rate of 2.5 x 10(5)M(-1)s(-1) and interrelationships of molecular parameters derived from known models for antibody-antigen interaction. PMID- 17275089 TI - Bacterial keratitis after penetrating keratoplasty: incidence, microbiological profile, graft survival, and visual outcome. AB - PURPOSE: To determine the incidence, microbiological profile, graft survival, and factors influencing graft survival after the development of bacterial keratitis after penetrating keratoplasty (PK). DESIGN: Retrospective case series. PARTICIPANTS: One hundred two patients (102 eyes) treated at a single center during a 5-year period. METHODS: Retrospective review of the medical records of every patient treated for culture-positive keratitis between January 1, 1998 and December 31, 2002 who previously had undergone penetrating keratoplasty at the King Khaled Eye Specialist Hospital. MAIN OUTCOME MEASURES: Graft survival and visual outcome. RESULTS: There were 2103 PKs performed and 102 (4.9%) cases of culture-positive keratitis during the study period. There were 168 bacterial isolates, of which 140 (83.3%) were gram positive, 28 (16.7%) were gram negative, and 1 (0.6%) was acid fast. Only 38 (37.3%) grafts remained clear after a mean follow-up of 985 days (range, 82-2284). The best graft survival was in eyes with PK for keratoconus (83.7%), whereas the poorest grat survival was for previously failed grafts (5.6%). By Kaplan-Meier analysis, there was an immediate steep decline in graft survival to 54.9%, followed by a slow decline to 47.2% by 1 year and 35.8% after 4 years. Factors associated with an increased risk of graft failure were the surgical indication for PK (P<0.001), increasing patient age (P = 0.004), smaller donor (P = 0.001) and recipient (P = 0.0003) graft size, history of previous microbial keratitis (P = 0.02) or endothelial rejection episodes (P = 0.02), and coexisting glaucoma (P = 0.001). The visual outcome was > or =20/40 in only 8 (8.2%) eyes and better than 20/200 in only 21 (21.6%) eyes. CONCLUSION: The development of bacterial keratitis after PK is a serious complication that is associated with a high incidence of graft failure and poor visual outcome. PMID- 17275090 TI - Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. AB - PURPOSE: To assess the relationship between cardiovascular disease and cardiovascular risk factors, other than smoking, and risk of long-term incident age-related macular degeneration (AMD). DESIGN: Population-based cohort study. PARTICIPANTS: There were 3654 baseline (1992-1994) participants aged > or = 49 years included in the Blue Mountains region, west of Sydney, Australia. Of these, 2335 (75% of survivors) were reexamined after 5 years (1997-1999) and 1952 (76% of survivors) after 10 years (2002-2004). METHODS: Stereoscopic color fundus photographs were graded using the Wisconsin Age-related Maculopathy Grading System. History, physical examination, and fasting blood samples provided data on possible risk factors. Age-related macular degeneration incidence was calculated using the Kaplan-Meier survival approach. Discrete linear logistic models were used to assess risk of incident AMD. Relative risks (RR) and 95% confidence intervals (CI) are presented after adjusting for age, gender, smoking, and other risk factors. MAIN OUTCOME MEASURE: Incident early and late AMD. RESULTS: Increasing high-density lipoprotein (HDL) cholesterol was inversely related to incident late AMD (RR per standard deviation [SD] increase, 0.74; 95% CI, 0.56 0.99). Elevated total/HDL cholesterol ratio predicted late AMD (RR per SD increase, 1.35; 95% CI, 1.07-1.70) and geographic atrophy (GA; RR per SD, 1.63; 95% CI, 1.18-2.25). Diabetes predicted incident GA (RR, 3.89; 95% CI, 1.36 11.08), but not neovascular AMD. History of stroke (RR 2.01; 95% CI, 1.12-3.58), or any cardiovascular disease (stroke, myocardial infarction, or angina; RR, 1.57; 95% CI, 1.13-2.16) predicted incident early AMD and incident indistinct soft or reticular drusen (RR, 2.38; 95% CI, 1.33-4.27 for stroke; RR, 1.80; 95% CI, 1.28-2.52 for any cardiovascular disease). Neither pulse pressure, systolic or diastolic blood pressure, or presence of hypertension at baseline were associated with incident AMD. CONCLUSIONS: Our findings provide some evidence of links between cardiovascular risk factors and AMD. Further prospective evaluation of these relationships is warranted, as these findings could have therapeutic implications. PMID- 17275091 TI - An investigation into copper catalyzed D-penicillamine oxidation and subsequent hydrogen peroxide generation. AB - D-Penicillamine is a potent copper (Cu) chelating agent. D-Pen reduces Cu(II) to Cu(I) in the process of chelation while at the same time being oxidized to D penicillamine disulfide. It has been proposed that hydrogen peroxide is generated during this process. However, definitive experimental proof that hydrogen peroxide is generated remains lacking. Thus, the major aims of these studies were to confirm and quantitatively assess the in vitro production of hydrogen peroxide during copper catalyzed D-penicillamine oxidation. The potential cytotoxic effect of hydrogen peroxide generation was also investigated in vitro against MCF-7 human breast cancer cells. Cell cytotoxicity resulting from the incubation of D penicillamine with copper was compared to that of D-penicillamine, copper and hydrogen peroxide. The mechanism of copper catalyzed D-penicillamine oxidation and simultaneous hydrogen peroxide production was investigated as a function of time, concentration of cupric sulfate or ferric chloride, temperature, pH, anaerobic condition and chelators such as ethylenediaminetetraacetic acid and bathocuproinedisulfonic acid. A simple, sensitive and rapid HPLC assay was developed to simultaneously detect D-penicillamine, its major oxidation product D penicillamine disulfide, and hydrogen peroxide in a single run. Hydrogen peroxide was shown to be generated in a concentration dependent manner as a result of D penicillamine oxidation in the presence of cupric sulfate. Chelators such as ethylenediaminetetraacetic acid and bathocuproinedisulfonic acid were able to inhibit D-penicillamine oxidation. The incubation of MCF-7 human breast cancer cells with D-penicillamine plus cupric sulfate resulted in the production of reactive oxygen species within the cell and cytotoxicity that was comparable to free hydrogen peroxide. PMID- 17275092 TI - The histamine H(4) receptor: a novel modulator of inflammatory and immune disorders. AB - All 4 known histamine receptors (H(1)R, H(2)R, H(3)R and H(4)R) have been used or proposed as therapeutic targets for varied diseases. This article reviews the recent progress in understanding the function of the recently described histamine receptor H(4)R in a variety of immune responses and the potential therapeutic value of H(4)R antagonists. The H(4)R is expressed primarily on cells involved in inflammation and immune response. It has effects on chemotaxis, as well as cytokine and chemokine production of mast cells, eosinophils, dendritic cells, and T cells. H(4)R antagonists, JNJ 7777120 and JNJ 10191584 (also known as VUF 6002) have been developed with excellent affinity and selectivity towards human and rodent H(4)R. These antagonists also demonstrate efficacy as anti inflammatory agents in vivo. H(4)R antagonists have shown promising activity in down-regulating immune responses in a range of animal disease models including acute inflammation, hapten-mediated colitis, and allergic airway inflammation. Due to its distribution on immune cells and its proven role in inflammatory functions, the H(4)R appears to be a therapeutic target for the treatment of a variety of immune disorders. PMID- 17275093 TI - The influence of electrode placement over the innervation zone on electromyographic amplitude and mean power frequency versus isokinetic torque relationships. AB - The purpose of this investigation was to examine the influence of electrode placement over the estimated innervation zone (IZ) for the vastus lateralis, as well as proximal and distal to the estimated IZ, on the torque-related patterns for electromyographic (EMG) amplitude and mean power frequency (MPF) during concentric and eccentric isokinetic muscle actions of the leg extensors. Eleven men performed randomly ordered, submaximal to maximal concentric and eccentric isokinetic muscle actions of the dominant leg extensors in 10% increments from 10 to 90% peak torque (PT). Surface EMG signals were recorded simultaneously from the vastus lateralis muscle with bipolar electrode arrangements placed over the estimated IZ, as well as proximal and distal to the estimated IZ. The results indicated that there were no consistent differences among the proximal, IZ, and distal electrode placement sites for the patterns of responses for absolute and normalized EMG amplitude and MPF versus torque, or the mean absolute and normalized EMG amplitude and MPF values. Thus, these findings suggested that during concentric and eccentric isokinetic muscle actions of the leg extensors, electrode placement over the estimated IZ for the vastus lateralis had no effect on the patterns of responses or mean values for absolute and normalized EMG amplitude and MPF versus torque. PMID- 17275094 TI - Stereotactic neurosurgical planning, recording, and visualization for deep brain stimulation in non-human primates. AB - Methodologies for stereotactic neurosurgery and neurophysiological microelectrode recordings (MER) in non-human primate research typically rely on brain atlases that are not customized to the individual animal, and require paper records of MER data. To address these limitations, we developed a software tool (Cicerone) that enables simultaneous interactive 3D visualization of the neuroanatomy, neurophysiology, and neurostimulation data pertinent to deep brain stimulation (DBS) research studies in non-human primates. Cicerone allows for analysis of co registered magnetic resonance images (MRI), computed tomography (CT) scans, 3D brain atlases, MER data, and DBS electrode(s) with predictions of the volume of tissue activated (VTA) as a function of the stimulation parameters. We used Cicerone to aid the implantation of DBS electrodes in two parkinsonian rhesus macaques, targeting the subthalamic nucleus in one monkey and the globus pallidus in the other. Cicerone correctly predicted the anatomical position of 79% and 73% of neurophysiologically defined MER sites in the two animals, respectively. In contrast, traditional 2D print atlases achieved 61% and 48% accuracy. Our experience suggests that Cicerone can improve anatomical targeting, enhance electrophysiological data visualization, and augment the design of stimulation experiments. PMID- 17275095 TI - Causal entropies--a measure for determining changes in the temporal organization of neural systems. AB - We propose a novel measure to detect temporal ordering in the activity of individual neurons in a local network, which is thought to be a hallmark of activity-dependent synaptic modifications during learning. The measure, called causal entropy, is based on the time-adaptive detection of asymmetries in the relative temporal patterning between neuronal pairs. We characterize properties of the measure on both simulated data and experimental multiunit recordings of hippocampal neurons from the awake, behaving rat, and show that the metric can more readily detect those asymmetries than standard cross correlation-based techniques, especially since the temporal sensitivity of causal entropy can detect such changes rapidly and dynamically. PMID- 17275096 TI - Psychopathology in children of bipolar parents. AB - BACKGROUND: Few studies have examined the psychopathological profiles of child offspring of bipolar parents. Such investigations are useful as a first step to identifying potential prodromal manifestations of bipolar disorder. METHODS: The presence of psychopathology in 37 children with at least one parent with bipolar I disorder and 29 demographically matched children with parents free of any DSM IV Axis I psychopathology was evaluated using the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U KSADS). RESULTS: Twenty-nine (78%) of 37 high-risk children were diagnosed with at least one DSM-IV Axis I diagnosis as compared to seven (24%) of 29 children of healthy control parents (Fisher's exact test, p < 0.0001, odds ratio=11, 95% CI=3.33, 33). Sixteen percent (N=6) of high-risk offspring met DSM-IV criteria for bipolar I disorder as compared to none of the healthy control offspring (Fisher's exact test, p < 0.03). High-risk offspring also had statistically significant elevations in rates of other affective and disruptive behavior disorders as well as subsyndromal manifestations of psychopathology. CONCLUSIONS: Children of bipolar parents had an elevated risk for developing bipolar and other psychiatric disorders. The study of children of bipolar parents who are at high risk for developing bipolar disorder themselves is essential to identify potential prodromal manifestations of the disorder and to eventually establish targeted early intervention strategies. Longitudinal studies to confirm the prodromal manifestations of bipolar disorder and risk factors associated with the development of specific diagnoses in children are needed. PMID- 17275097 TI - Cervical leukocyte sub-populations in idiopathic preterm labour. AB - OBJECTIVE: To investigate cervical epithelial leukocyte sub-populations in pregnant women with a history of idiopathic preterm labour. METHODS: A prospective observational study was undertaken of 106 women with a past history of idiopathic preterm delivery following spontaneous labour. A cytobrush was used to sample the epithelium of the cervix at 12-16 weeks of gestation and again 8 weeks later. All women had investigations for cervical and vaginal infection as well as serial transvaginal ultrasonography of their cervix; the mode and gestation at delivery were recorded. Leukocyte sub-populations were examined using immunocytochemistry, and the number of leukocytes per total cell count was calculated. MAIN OUTCOME MEASURES: Cervical epithelial leukocytes populations were (1) described in pregnancy, (2) observed over increasing gestation, (3) analysed in women who developed marked cervical shortening and (4) in those whose preterm labour recurred. RESULTS: There was no significant change in cervical epithelial leukocyte populations during the second trimester of pregnancy. There was no association between cervical leukocytes and cervical shortening. Women with idiopathic preterm labour that recurred had fewer cervical macrophages at the beginning of the second trimester of pregnancy than those whose subsequent pregnancy progressed beyond 35 weeks of gestation. CONCLUSIONS: Cervical epithelial macrophages may serve to prevent recurrent preterm labour, possibly by preventing ascending infection. PMID- 17275099 TI - Sequence and phylogenetic analysis of interleukin (IL)-1beta-encoding genes of five avian species and structural and functional homology among these IL-1beta proteins. AB - Interleukin (IL)-1beta-encoding regions of chicken, duck, goose, turkey and pigeon were cloned and sequenced. Each IL-1beta-encoding region of chicken, duck, goose and turkey is 804 nucleotides long and encodes IL-1beta protein that is 268 amino acids. Pigeon IL-1beta-encoding region is 810 nucleotides long and encodes IL-1beta protein that is 270 amino acids. Two one-nucleotide and one four nucleotide insertions of pigeon IL-1beta-encoding region sequence were found, resulting in two amino acid insertions in pigeon IL-1beta. Pairwise sequence analysis showed that the sequence identities of IL-1beta-encoding genes ranged from 77% to 99%, which were also found for IL-1beta protein sequence identities, with an average level of both sequence identities of 89%. Phylogenetic analysis indicated that IL-1beta-encoding regions and the encoded proteins of chicken, duck, goose and turkey clustered together and evolved into a distinct phylogenetic lineage from that of pigeon which evolved into a second lineage. The results from the binding reaction of antiserum against each recombinant IL-1beta (r IL-1beta) protein to homologous or heterologous rIL-1beta, the enhancement levels of K60 mRNA expression in rIL-1beta-treated DF-1 cells or the reduction levels of K60 mRNA expression in DF-1 cells treated with rIL-1beta that was preincubated with homologous or heterologous antiserum showed that all five rIL 1beta were functional active and shared significantly structural and functional homology. PMID- 17275098 TI - Failure of antigen-stimulated gammadelta T cells and CD4+ T cells from sensitized cattle to upregulate nitric oxide and mycobactericidal activity of autologous Mycobacterium avium subsp. paratuberculosis-infected macrophages. AB - The function of gammadelta T cells during ruminant paratuberculosis (Johne's disease) is presently unknown. An ex vivo system was used to test the hypothesis that gammadelta T cells are capable of activating Mycobacterium avium subsp. paratuberculosis-(M. paratuberculosis)-infected macrophages. Peripheral blood derived macrophages were infected in vitro with live M. paratuberculosis, and autologous LN-derived gammadelta T cells or CD4+ T cells were co-cultured with infected macrophages for 48h, at which time bacterial survival as well as production of nitrites and IFN-gamma was evaluated. Incubation of M. paratuberculosis-infected macrophages with autologous gammadelta T cells did not result in reduced intracellular bacterial viability compared to infected macrophage cultures without added T cells. IFN-gamma production by-infected cultures containing added gammadelta T cells was not enhanced compared to that of infected macrophages alone. Although infection of macrophage cultures caused increased production of nitrites at both post-infection day (PID) 0 and PID 60, the addition of gammadelta T cells did not further increase nitrite production. In contrast, addition of PPD-stimulated CD4+ T cells obtained at PID 60 to M. paratuberculosis-infected macrophages resulted in significantly increased IFN gamma production compared to cultures without added T cells or cultures containing unstimulated CD4+ T cells or unstimulated or antigen-stimulated gammadelta T cells. However, the increased production of IFN-gamma by co-cultures containing PPD-stimulated CD4+ T cells did not result in increased bacterial killing or increased production of nitrites compared to cultures without added T cells. In additional in vitro experiments, M. paratuberculosis-infected macrophages, but not uninfected macrophages, were unable to increase nitrite production when stimulated with recombinant IFN-gamma. Taken together, the data suggest that (1) gammadelta T cells do not produce significant IFN-gamma and do not significantly increase NO production from M. paratuberculosis-infected macrophages in vitro, (2) the production of significant IFN-gamma by antigen stimulated CD4+ T cells from infected calves is insufficient to enhance mycobacterial killing or nitrite production by infected macrophages, and (3) macrophages may have an impaired NO response following intracellular M. paratuberculosis infection, even in the presence of significant concentrations of IFN-gamma. PMID- 17275100 TI - Local pulmonary immune stimulation by the Toll-like receptor 2 and 6 ligand MALP 2 in rats is age dependent. AB - Recent studies indicate that the pulmonary immune response in humans and experimental animals is different in newborn, adult and elderly age groups. The aim of this study was to investigate the influence of age on the leukocyte composition in different lung compartments and peripheral blood of weaned and adult rats. A mycoplasma-like inflammatory response was mimicked by intratracheal application of the synthetic macrophage-activating lipopeptide-2 (MALP-2) which activates macrophages and other cells via the Toll-like receptor (TLR) 2 and 6. TLR 2 and 6 mRNA expressions were investigated by semiquantitative RT-PCR in cells of the bronchoalveolar lavage (BAL) and lung interstitium. Weaned Lewis rats (3-4 weeks old) and adults (12-14 months old) were treated with vehicle control or MALP-2. Cytokines and cell infiltration were measured in the BAL and lung interstitium. In control rats, no differences in TLR 2 and 6 mRNA expression level were found between the age groups. After MALP-2 treatment, the maximum of MCP-1 concentration in the BAL fluid was reached in weaned rats after 4h and in adults after 2h. The TNF-alpha maximum was measured after 2h in both age groups. Three days after MALP-2 the numbers of different leukocyte subsets were significantly increased in the BAL of both groups. In contrast, in the lung interstitium MALP-2 induced a leukocyte increase in adult rats but not in weaned rats. In conclusion, data on pulmonary immune responses from one age group and one lung compartment should not be generalized or extrapolated to other groups. PMID- 17275101 TI - Trypanosoma cruzi-triggered meningoencephalitis is a CCR1/CCR5-independent inflammatory process. AB - Encephalitis rarely occurs during acute Trypanosoma cruzi infection. However, the central nervous system (CNS) is the major site of infection reactivation in immunocompromised patients. We show that the acute T. cruzi-triggered CD8 enriched meningoencephalitis paralleled the in situ expression of CCL3/MIP-1alpha and CCL5/RANTES mRNA. The frequency of CCR5-bearing cells was increased among peripheral blood mononuclear cells (PBMC) of infected mice. Further, CCL5/RANTES driven in vitro PBMC migration was partially abrogated by the CCR1/CCR5 antagonist Met-RANTES. However, Met-RANTES treatment of infected mice altered neither parasitism nor intensity and nature of the CNS inflammation, indicating that T. cruzi-elicited meningoencephalitis is a CCR1/CCR5 independent process. PMID- 17275102 TI - The organizing principles of neuronal avalanches: cell assemblies in the cortex? AB - Neuronal avalanches are spatiotemporal patterns of neuronal activity that occur spontaneously in superficial layers of the mammalian cortex under various experimental conditions. These patterns reflect fast propagation of local synchrony, display a rich spatiotemporal diversity and recur over several hours. The statistical organization of pattern sizes is invariant to the choice of spatial scale, demonstrating that the functional linking of cortical sites into avalanches occurs on all spatial scales with a fractal organization. These features suggest an underlying network of neuronal interactions that balances diverse representations with predictable recurrence, similar to what has been theorized for cell assembly formation. We propose that avalanches reflect the transient formation of cell assemblies in the cortex and discuss various models that provide mechanistic insights into the underlying dynamics, suggesting that they arise in a critical regime. PMID- 17275103 TI - Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death. AB - AMPA receptors mediate fast synaptic transmission at excitatory synapses in the CNS and are crucial during neuronal development, synaptic plasticity and structural remodeling. AMPA receptors lacking GluR2 subunits are permeable to Ca(2+) and Zn(2+). Ca(2+) permeation through AMPA receptors is crucial in several forms of synaptic plasticity and cell death associated with neurological diseases and disorders. The subunit composition and Ca(2+) permeability of AMPA receptors are not static, but they are dynamically remodeled in a cell- and synapse specific manner during development and in response to neuronal activity, sensory experience and neuronal insults. Exciting new research shows that these changes arise not only because of regulated expression of the AMPA receptor subunit GluR2, but also as a consequence of RNA editing, receptor trafficking and dendritic protein synthesis. This article reviews new insights into the role of Ca(2+)-permeable AMPA receptors in neuronal function and survival. PMID- 17275104 TI - Induction of potent and long-lasting CD4 and CD8 T-cell responses against hepatitis C virus by immunization with viral antigens plus poly(I:C) and anti CD40. AB - Development of vaccination strategies against hepatitis C virus (HCV) is of paramount importance. With this aim, we tested the ability of dendritic cell activating reagents polyinosinic-polycytidylic acid (poly(I:C)) and anti-CD40, as adjuvants to induce T-cell responses against HCV. Immunization of mice with these adjuvants induced dendritic cell maturation in vivo. Also, joint administration of poly(I:C) and anti-CD40 plus HCV antigens had a synergistic effect on the induction of anti-HCV T-cell responses. CD4 responses displayed a Th1 cytokine profile, and CD8 responses could be induced by immunization with a minimal CD8 epitope. Addition of a low amount of NS3 protein (as a source of Th epitopes) to the immunization mixture enhanced CD8 responses, whereas immunization with higher doses of NS3 induced both CD4 and CD8 responses. Surprisingly, immunization with NS3 protein but not with CD8 epitopes was able to induce CD8 responses and able to recognize cells expressing HCV antigens endogenously. Moreover, immunization with these adjuvants activated NK cells, which in turn helped to induce Th1 responses. Finally, this combined immunization protocol afforded long-lasting T cell responses, suggesting that this strategy may prove to be useful in vaccination and/or treatment of HCV infection. PMID- 17275105 TI - Differences in locomotor behavior revealed in mice deficient for the calcium binding proteins parvalbumin, calbindin D-28k or both. AB - We investigated the role of the two calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB) in the locomotor activity and motor coordination using null mutant mice for PV (PV-/-), CB (CB-/-) or both proteins (PV-/-CB-/-). These proteins are expressed in distinct, mainly non-overlapping populations of neurons of the central and peripheral nervous system and PV additionally in fast-twitch muscles. In a test measuring repeated locomotor activity during 18-20 days, the analysis revealed a slightly increased activity in mice lacking either protein, while the lack of both decreased the number of beams crossed during active periods. An increase in the characteristic speed during the first 8 days could be attributed to PV-deficiency, while the elimination of CB in CB-/- and double-KO mice decreased the percentage of fast movements at all time points. In the latter, additionally a reduction of the fastest speed was observed. The alterations in locomotor activity (fast movements, fastest speed) strongly correlate with the impairment in locomotor coordination in mice deficient for CB evidenced in the runway assay and the rotarod assay. The graded locomotor phenotype (CB>PV) is qualitatively correlated with alterations in Purkinje cell firing reported previously in these mice. The presence or absence of either protein did not affect the spontaneous locomotor activity when animals were placed in a novel environment and tested only once for 30 min. In summary, the lack of these calcium-binding proteins yields characteristic, yet distinct phenotypes with respect to locomotor activity and coordination. PMID- 17275108 TI - To use BEST as an acronym for another cardiological trial may not be the best idea. PMID- 17275106 TI - Stable expression of Cryptosporidium parvum glycoprotein gp40/15 in Toxoplasma gondii. AB - Cryptosporidium is a cause of diarrheal disease worldwide. Parasite glycoproteins involved in invasion of Cryptosporidium into host cells have been investigated as possible targets for effective interventions against this parasite. One of these, Cpgp40/15, is expressed as a precursor protein that is cleaved by a parasite derived furin-like protease activity into gp15, a glycophosphatidyl inositol anchored surface protein, and gp40, that associates with gp15 and binds to host cells. Investigation of the functions of these glycoproteins requires an expression system that can produce similar glycosylation patterns to the native antigens. Previous work demonstrated that Cpgp40/15 transiently expressed in Toxoplasma gondii was appropriately localized and glycosylated. In this study, T. gondii stable transfectants expressing gp40/15, gp15, gp40 and hemagglutinin (HA) tagged gp40 were generated. T. gondii recombinant gp40HA and gp40/15 (recTggp40HA and recTggp40/15) were isolated from infected cells by HA affinity chromatography and Helix pomatia lectin affinity chromatography, respectively. Mass spectrometry confirmed that recTggp40-HA and native Cpgp40 were similarly glycosylated. Like native Cpgp40/15, recTggp40/15 could be cleaved into the gp40 and gp15 products by human furin or by a furin-like protease activity in T. gondii tachyzoite lysates. However, processing was inefficient in intact tachyzoites. Unlike the N terminus of native Cpgp40/15, which appears to be processed following signal peptide cleavage, the N-terminus of recTggp40/15 began at the predicted signal sequence cleavage site, 11 amino acids upstream of the N-terminus of native Cpgp40. The ability to express and isolate appropriately glycosylated Cryptosporidium glycoproteins will enable further investigations into host parasite interactions of this important pathogen. PMID- 17275107 TI - Reduced-energy diet improves survival of obese KKAy mice with viral myocarditis: induction of cardiac adiponectin expression. AB - Obesity is an important risk factor for heart disease. Whether weight loss affects the severity of heart failure induced by viral myocarditis is a matter of debate. We hypothesized that weight loss could improve cardiac dysfunction by inducing cardiac expression of a cardioprotective cytokine, adiponectin. We examined the relationship between weight loss by food restriction and heart failure due to viral myocarditis in obese KKAy mice. We intraperitoneally injected encephalomyocarditis virus (500 plaque-forming units/mouse) into KKAy mice fed ad libitum as a control (CF) or 60% restriction of that eaten by ad libitum (RF). The 14-day survival rate was 0% in FF, whereas it was 23% in RF (P<0.01). Heart weight/body weight ratio in RF was lower than that in FF on day 5 after viral inoculation (P<0.05). Histological scores for myocardial necrosis and inflammation on day 5 were significantly lower in RF than in FF (P<0.05). Circulating adiponectin level on day 0 was significantly elevated in RF compared with that in FF (32+9 vs. 22+2 microg/mL, P<0.05). Comparative expression of cardiac adiponectin mRNA in RF was significantly higher than that in FF (5.1+0.3 vs. 1+0.2, P<0.05). Cardiac tumor necrosis factor-alpha (TNF-alpha) mRNA in RF was significantly decreased compared with that in FF on day 5 (P<0.05). Cardiac expression of nuclear factor kappa B was reduced and that of peroxisome proliferator-activated receptor gamma mRNA was increased in RF in comparison with FF on day 0. Cardiac adiponectin mRNA was negatively correlated with cardiac TNF alpha mRNA (r=-0.555; P=0.0097). Weight loss improved the survival and myocardial damage in obese mice with viral myocarditis, with cardiac induction of adiponectin. The induction of adiponectin might provide benefit through a cardioprotective effect against acute heart failure due to viral myocarditis in obese subjects. PMID- 17275109 TI - Remission of brucella endocarditis in a patient with mitral valve mechanical prosthesis by antibiotic therapy alone: a case report. PMID- 17275111 TI - Quality incentives for GPs in a regulated market. AB - This paper analyses whether GPs in a capitation system have incentives to provide quality even though health is a credence good. A model is developed where the quality of the service varies due to inherent differences between the GPs and rational patients make choices based on the outcome of treatment. We find that it is difficult to provide appropriate incentives since the search activity of patients offsets direct effects of a change in reimbursement. Variation in the inherent ability of the GPs is good since it increases the search activity of the patients and the optimal reimbursement scheme is inversely proportional to the dispersion in types. Finally, we find that offering a menu of contracts can potentially increase social welfare above the level of a simple capitation regime, but it tends to lead to a higher variation in quality levels. PMID- 17275110 TI - Improved exercise tolerance and cardiac function in severe chronic heart failure patients undergoing a supervised exercise program. AB - BACKGROUND: Exercise intolerance is a widespread and serious problem in chronic heart failure (CHF) patients. However, the impact of a supervised exercise and rehabilitation program on exercise tolerance and cardiac performance in severe CHF patients has not yet been fully investigated. METHODS: Of 56 consecutive patients with severe CHF (New York Heart Association functional class III, Stage D) 44 underwent a hospital-based supervised 18-week, cardiac exercise and rehabilitation program (exercise group), and 12 did not (control group). Cardiac performance was assessed by a 6-minute walk test, peak exercise VO(2), exercise duration time, resting and immediate post peak exercise stroke index (SI), cardiac index (CI) and systemic vascular resistance (SVR), before and after exercise. RESULTS: Both groups were comparable regarding baseline clinical characteristics. Post exercise training, functional and hemodynamic parameters improved significantly in the exercise group compared to controls. A highly significant interaction between the groups and change was found in the 6-minute walk test (p<0.001), exercise test duration (p<0.001), METs during exercise (p<0.001), immediate post peak exercise CI (0.016), delta peak VO(2) (p=0.028), and immediate post peak exercise SVR (p=0.045). CONCLUSIONS: A hospital-based supervised exercise and rehabilitation program significantly improves functional and hemodynamic parameters in severe CHF patients, and may partially contribute to better physical conditioning detected in these patients after exercise training. PMID- 17275112 TI - A dosimetric comparison of non-coplanar IMRT versus Helical Tomotherapy for nasal cavity and paranasal sinus cancer. AB - PURPOSES: To determine if there are clinically significant differences between the dosimetry of sinus tumors delivered by non-coplanar LINAC-based IMRT techniques and Helical Tomotherapy (HT). HT is capable of delivering highly conformal and uniform target dosimetry. However, HT lacks non-coplanar capability, which is commonly used for linear accelerator-based IMRT for nasal cavity and paranasal sinus tumors. METHODS AND MATERIALS: We selected 10 patients with representative early and advanced nasal cavity and paranasal sinus malignancies treated with a preoperative dose of 50 Gy/25 fractions without coverage of the cervical lymphatics for dosimetric comparison. Each plan was independently optimized using either Corvus inverse treatment planning system, commissioned for a Varian 2300 CD linear accelerator with 1cm multileaf collimator (MLC) leaves, or the HT inverse treatment planning system. A non coplanar seven field technique was used in all Corvus plans with five mid sagittal fields and two anterior oblique fields as described by Claus et al. [F. Claus, W. De Gersem, C. De Wagter, et al., An implementation strategy for IMRT of ethmoid sinus cancer and bilateral sparing of the optic pathways, Int J Radiat Oncol Biol Phys 51 (2001) 318-331], whereas only coplanar beamlets were used in HT planning. Dose plans were compared using DVHs, the minimum PTV dose to 1cm3 of the PTV, a uniformity index of planned treatment volume (PTV), and a comprehensive quality index (CQI) based on the maximum dose to optical structures, parotids and the brainstem which were deemed as the most critical adjacent structures. RESULTS: Both planning systems showed comparable PTV dose coverage, but HT had significantly higher uniformity (p<0.01) inside the PTV. The CQI for all organs at risk were equivalent except ipsilateral lenses and eyes, which received statistically lower dose from HT plans (p<0.01). CONCLUSIONS: Overall HT provided equivalent or slightly better normal structure avoidance with a more uniform PTV dose for nasal cavity and paranasal sinus cancer treatment than non-coplanar LINAC-based IMRT. The disadvantage of coplanar geometry in HT is apparently counterbalanced by the larger number of fields. PMID- 17275113 TI - Social support schemas, trait anger, and cardiovascular responses. AB - This study examined the influence of activated support schemas on cardiovascular reactivity (CVR) during an anger-recall interview. Eighty Chinese female undergraduates wrote about a supportive tie or a casual acquaintance and subsequently disclosed an anger-provoking event while their heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Compared to participants in the 'acquaintance' condition, those in the 'support' condition showed lower HR, SBP and DBP reactivity, as well as smaller state anger increases and less negative appraisals of the recalled anger event. Reactivity increased as a function of trait anger. High trait anger individuals also had greater increases in state anger and more negative appraisals of the recalled event compared to their low trait anger counterparts. Support schema activation reduced the effects of trait anger on CVR such that high trait anger individuals in the 'support' condition had significantly lower CVR compared to high trait anger individuals in the 'acquaintance' condition. These findings suggest that social support schemas may have beneficial effects even in the absence of actual, enacted support. PMID- 17275114 TI - Differential characteristics of HIV-based versus SIV-based lentiviral vector systems: Gene delivery to neurons and axonal transport of expressed gene. AB - The differential characteristics of lentiviral vectors based on human and simian immunodeficiency viruses (HIV and SIV) were investigated in rats and monkeys. Each vector was injected into the striatum, and the expression patterns of the marker gene green fluorescent protein (GFP) were analyzed in the basal ganglia. With respect to the capability of gene delivery to neural cells, the HIV-based vector exhibited a higher tropism to neurons than to astroglias in the striatum, and vice versa for the SIV-based vector. The preferential direction of axonal transport of striatally expressed GFP was also examined in the present study. The HIV-based vector allowed for both anterograde transport via the striatopallidal and striatonigral pathways and retrograde transport via the nigrostriatal pathway. The GFP labeling of axon terminals through anterograde transport was apparent regardless of the animal species, while that of neuronal cell bodies through retrograde transport was much more prominent in monkeys than in rats. As for the SIV-based vector, on the other hand, evidence for anterograde transport was obtained much more markedly in monkeys than in rats, and only weak or no retrograde transport occurred in either monkeys or rats. Our results indicate that HIV-based, but not SIV-based, lentiviral vectors possess the high tropism to neurons and permit retrograde transport of an expressed gene, especially in primates. The latter property might carry a potential benefit in gene therapy for Parkinson's disease, as stereotaxic injections of the vectors could be performed into the striatum, spatially larger than the substantia nigra, with greater certainty. PMID- 17275115 TI - No association between the ERBB3 gene and schizophrenia in a Japanese population. AB - There is cumulative evidence that neuregulin 1 (NRG1) is a susceptibility gene for schizophrenia. Postmortem studies on brains from schizophrenia patients have revealed changes in the mRNA expression levels of v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), one of the NRG1 receptor genes. These observations suggest that NRG1-ERBB signaling is involved in the pathogenesis of schizophrenia. To assess whether the ERBB3 gene could be implicated in vulnerability to schizophrenia, we conducted a case-control (399 patients and 438 controls) association study in Japanese subjects. There were no significant association between the polymorphisms or haplotypes of ERBB3 and schizophrenia. The present study shows that ERBB3 does not play a major role in conferring susceptibility to schizophrenia in the Japanese population. PMID- 17275116 TI - Food poisoning associated with pumilacidin-producing Bacillus pumilus in rice. AB - Food poisoning caused by other Bacillus species than B. cereus has been described, but the toxins involved have rarely been isolated. Endospores will survive heat treatment and will germinate and multiply in cooked foods producing toxins under appropriate conditions. We describe a small food poisoning outbreak where three people became ill after a dinner in a Chinese restaurant. Acute symptoms including dizziness, headache, chills and back pain developed during the meal, and a few hours later they got stomach cramps and diarrhoea which lasted for several days. Cooked, reheated rice was the prime suspect of the food poisoning, and from the rice large numbers of Bacillus pumilus were isolated. The isolated B. pumilus strain was found to produce a complex of lipopeptides known as pumilacidins with the highest amounts produced at 15 degrees C. This is the first report on isolation of a pumilacidin-producing B. pumilus strain from food implicated in food poisoning and characterization of the organism and the toxin complex involved. PMID- 17275117 TI - Highly efficient gene targeting in the Aspergillus niger kusA mutant. AB - Gene targeting frequencies in Aspergillus niger are often very low and hamper efficient functional genomics in this biotechnologically important fungus. Deletion of the A. niger kusA gene encoding the ortholog of the Ku70 protein in other eukaryotes, dramatically improved homologous integration efficiency and reached more than 80% compared to 7% in the wild-type background, when 500bp homologous flanks were used. Furthermore, the use of the DeltakusA strain resulted in a high frequency of heterokaryon formation (70%) in primary transformants in the case disrupting an essential gene. Deletion of kusA had no obvious effect on the growth of the fungus, but renders the DeltakusA strain 10 times more sensitive to X-ray irradiation and two to three times more sensitive to UV exposure. The highly efficient gene targeting in combination with the A. niger genome sequence allows a systematic approach to generate gene knockouts and will help in improving the capacities of A. niger as producer of commercially interesting proteins and metabolites. PMID- 17275118 TI - Inositol-1-phosphate synthetase mRNA as a new target for antisense inhibition of Mycobacterium tuberculosis. AB - The need for novel antimicrobial agents to combat the emergence of multi-drug resistant strains of Mycobacterium tuberculosis is a worldwide urgency. This study has investigated the effects on phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODNs) against the mRNA of inositol-1-phosphate synthase, the key enzyme in the first step in inositol synthesis. Inositol is utilized by M. tuberculosis in the production of its major thiol, which is an antioxidant that helps M. tuberculosis to get rid of reactive oxygen species and electrophilic toxins. Real-time RT-PCR analysis revealed that mRNA expression of inositol-1-phosphate (I-1-P) synthase was significantly reduced upon addition of 20 microM PS-ODNs. Treatment with antisense PS-ODNs also reduced the level of mycothiol and the proliferation of M. tuberculosis and enhanced susceptibility to antibiotics. The experiments indicated that the antisense PS-ODNs could enter the cytoplasm of M. tuberculosis and inhibit the expression of I-1-P synthase. This study demonstrates that the M. tuberculosis I-1-P synthase is a target for the development of novel antibiotics and PS-ODN to I-1-P synthase is a promising antimycobaterial candidate. PMID- 17275119 TI - Effect of elevated dissolved carbon dioxide concentrations on growth of Corynebacterium glutamicum on D-glucose and L-lactate. AB - The effect of increased dissolved carbon dioxide concentrations on growth of Corynebacterium glutamicum was studied with continuous turbidostatic cultures. The carbon sources were either l-lactate or d-glucose. To increase the dissolved carbon dioxide concentration the carbon dioxide partial pressure of the inlet gas stream pCO2,IN was increased stepwise from 0.0003 bar (air) up to 0.79 bar, while the oxygen partial pressure of the inlet gas stream was kept constant at 0.21 bar. For each resulting carbon dioxide partial pressure pCO2 the maximum specific growth rate mu(max) was determined from the feed rate resulting from the turbidostatic control. On d-glucose and pCO2 up to 0.26 bar, mu(max) was mostly constant around 0.58 h(-1). Higher pCO2 led to a slight decrease of mu(max). On l lactate mu(max) increased gradually with increasing carbon dioxide partial pressures from 0.37 h(-1) under aeration with air to a maximum value of 0.47 h( 1) at a pCO2 of 0.26 bar. At very high pCO2 (0.81 bar) mu(max) decreased down to 0.35 h(-1) independent of the carbon source. PMID- 17275120 TI - Molecular characterisation of the virulent canine coronavirus CB/05 strain. AB - This paper characterises a virulent strain (CB/05) of canine coronavirus (CCoV) isolated from the internal organs of pups that had died of a systemic disease without evidence of other common canine pathogens. High viral RNA titres were detected in the internal organs by a real-time RT-PCR assay specific for CCoV type II. Sequence analysis of the 3' end (8.7kb) of the genomic RNA of strain CB/05 revealed conserved structural as well as non-structural proteins, with the exception of a truncated form of non-structural protein 3b. The exceptional form was due to a 38-nucleotide deletion and a frame shift in ORF3b that introduced an early stop codon. By phylogenetic analysis of the structural proteins, the spike (S) protein was found to cluster with feline coronavirus type II strain 79-1683, whereas, the envelope (E), membrane (M) and nucleocapsid (N) proteins segregated together with the reference strain Purdue of transmissible gastroenteritis virus of swine. PMID- 17275121 TI - Outcomes of pregnancies affected by impaired glucose tolerance. AB - OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with an increase in both maternal and neonatal morbidity. There remains uncertainty, however, about the diagnostic criteria for GDM. We compared pregnancy outcomes across three groups of women, with the aim of establishing a threshold for diagnosis of GDM at our institution. METHODS: Women with a glucose tolerance test (GTT) were identified on the hospital's pathology database. Those women with a singleton pregnancy, in whom a GTT had demonstrated a fasting value /=7.8mmol/L and who confined /=5.5mmol/L and/or 2h >/=7.8mmol/L on 75g GTT. PMID- 17275122 TI - High prevalence of glucose metabolism disturbance in patients with lichen planus. AB - AIM: To establish the prevalence of diabetes mellitus (DM) and insulin resistance in patients with lichen planus (LP), and to examine whether diabetic status showed any relation with the type of LP. PATIENTS AND METHODS: Thirty patients with LP and 30 age, weight, and sex matched volunteers were included. Serum fasting glucose, insulin, hemoglobin A1c levels were determined, a standard oral glucose tolerance test (OGTT) was performed. RESULTS: Of patients with LP, eight (26.7%) had DM (four newly diagnosed), however, only one (3.33%) diagnosed as DM in control group (p=0.007). Six patients (20.0%) with LP and four healthy persons (13.3%) had IGT (p>0.05). Glucose metabolism disturbance (DM+IGT) was detected in 14 (46.7%) of the patients and in 5 (16.7%) of the controls (p=0.026). HbA1c, fasting serum glucose, and insulin resistance (HOMA) were statistically higher in patients compared to controls. CONCLUSION: Our finding documented that approximately one half of the patients with LP had glucose metabolism disturbance, and one fourth had DM. We believe that further studies are needed to explain this close relationship between DM and LP. PMID- 17275123 TI - Haptoglobin polymorphism and diabetic retinopathy in Brazilian patients. AB - Haptoglobin (Hp) is an acute phase protein with antioxidant and immunomodulatory properties. Three main genotypes/phenotypes (Hp1-1, Hp2-1 and Hp2-2) show distinct efficiencies in these activities and have been associated with susceptibility and outcome in several diseases, including diabetes mellitus (DM). It has been suggested that Hp polymorphism may influence the development of retinopathy, an important microvascular complication in DM. In order to investigate this association in a Brazilian population, we determined the Hp genotypes of 317 diabetic patients with at least 10 years of disease. The patients were classified as DM-type 1 and 2, with and without diabetic retinopathy (DR). The Hp genotype frequencies of the different patient groups and of a control group consisting of 142 healthy individuals who had previously been studied were compared. No significant differences were observed for the three Hp genotypes. Hemoglobin A1c levels, systolic blood pressure (SBP), diastolic blood pressure (DBP) and duration of diabetes, which are potential risk factors for DR, were also compared. Again no significant differences were observed for the three Hp genotypes. Thus, we conclude that this polymorphism is not associated with the presence of DR in the Brazilian population studied here. PMID- 17275125 TI - Met-thodology. PMID- 17275124 TI - High hepatic glutathione stores alleviate Fas-induced apoptosis in mice. AB - BACKGROUND/AIMS: The agonistic Jo2 anti-Fas antibody reproduces human fulminant hepatitis in mice. We tested the hypothesis that enhancing hepatic glutathione (GSH) stores may prevent Jo2-induced apoptosis. METHODS: We fed mice with a normal diet or a sulfur amino acid-enriched (SAA(+)) diet increasing hepatic GSH by 63%, and challenged these mice with Jo2. RESULTS: The SAA(+) diet markedly attenuated the Jo2-mediated decrease in hepatic GSH and the increase in the oxidized glutathione (GSSG)/GSH ratio in cytosol and mitochondria. The SAA(+) diet prevented protein kinase Czeta (PKCzeta) and p47(phox) phosphorylations, Yes activation, Fas-tyrosine phosphorylation, Bid truncation, Bax, and cytochrome c translocations, the mitochondrial membrane potential collapse, caspase activation, DNA fragmentation, hepatocyte apoptosis, and mouse lethality after Jo2 administration. The protective effect of the SAA(+) diet was abolished by a small dose of phorone decreasing hepatic GSH back to the levels observed in mice fed the normal diet. Conversely, administration of GSH monoethyl ester after Jo2 administration prevented hepatic GSH depletion and attenuated toxicity in mice fed with the normal diet. CONCLUSIONS: The SAA(+) diet preserves GSSG/GSH ratios, and prevents PKCzeta and p47(phox) phosphorylations, Yes activation, Fas-tyrosine phosphorylation, mitochondrial permeabilization, and hepatic apoptosis after Fas stimulation. GSH monoethyl ester is also protective, suggesting possible clinical applications. PMID- 17275127 TI - HCV NS5A inhibits interferon-alpha signaling through suppression of STAT1 phosphorylation in hepatocyte-derived cell lines. AB - BACKGROUND/AIMS: HCV NS5A appears to play an important role in HCV resistance to IFN-alpha but the molecular mechanism is not fully elucidated. Most studies regarding the involvement of signal transducer and activator of transcription 1 (STAT1) in inhibition of IFN-alpha signaling by NS5A were performed in non hepatic cell lines and their relevance may be debatable. METHODS: We analyzed the effects of NS5A on IFN-alpha signaling through STAT1 phosphorylation in three hepatocyte-derived cell lines, Hep3B, J5 and Huh7. Interaction of NS5A and STAT1 was also investigated with co-immunoprecipitation and confocal microscopy. RESULTS: IFN-alpha induces STAT1 activation in Hep3B cells in a dose- and time dependent manner. Transient or stable NS5A expression inhibits STAT1 phosphorylation in a dose-dependent manner in hepatocyte-derived cell lines, whereas the levels of STAT1 phosphorylation remain unchanged in non-hepatocyte HeLa and COS7 cells despite increasing amounts of NS5A. The NS5A may interact with STAT1, specifically, the N-terminal 488 amino acids of STAT1. Furthermore, NS5A inhibits activation of interferon-stimulated gene factor 3 (ISGF3) and interferon-stimulated response element (ISRE)-driven gene expression, as demonstrated by electrophoretic mobility shift assay and luciferase assay, respectively. CONCLUSIONS: NS5A may interact with STAT1 and inhibit IFN-alpha signaling through suppression of STAT1 phosphorylation specifically in hepatocyte derived cells. PMID- 17275126 TI - Identification of a gene-pathway associated with non-alcoholic steatohepatitis. AB - BACKGROUND/AIMS: We have integrated gene expression profiling of liver biopsies of NASH patients with liver samples of a mouse model of steatohepatitis (MAT1A KO) to identify a gene-pathway associated with NASH. METHODS: Affymetrix U133 Plus 2.0 microarrays were used to evaluate nine patients with NASH, six patients with steatosis, and six control subjects; Affymetrix MOE430A microarrays were used to evaluate wild-type and MAT1A-KO mice at 15 days, 1, 3, 5 and 8 months after birth. Transcriptional profiles of patients with NASH and MAT1A-KO mice were compared with those of their proficient controls. RESULTS: We identified a gene-pathway associated with NASH, that accurately distinguishes between patients with early-stage NASH and controls. Patients with steatosis have a gene expression pattern intermediate between that of NASH and controls. Promoter analysis revealed that 34 of the genes associated with NASH contained an Sp1 element. We found that Sp1 binding to these genes is increased in MAT1A-KO mice. Sp1 is also hyperphosphorylated in MAT1A-KO as well as in patients with NASH and steatosis. CONCLUSIONS: A gene-pathway associated with NASH has been identified. We speculate that hyperphosphorylation of Sp1 may be involved in the genesis of steatosis and that other factors, such as oxidative stress, may trigger its progression to NASH. PMID- 17275128 TI - Decreased leukocyte recruitment in the mesenteric microcirculation of rats with cirrhosis is partially restored by treatment with peginterferon: an in vivo study. AB - BACKGROUND/AIMS: Patients with liver cirrhosis are predisposed to develop bacterial infections. An essential process in inflammatory responses is the recruitment of circulating leukocytes through the activation of adhesion molecules. Interferon-alpha2a is a cytokine reported to influence the expression of adhesion molecules. We investigated the effect of peginterferon-alpha2a (PegIFN-alpha(2a)) in vivo on the leukocyte recruitment in the mesenteric microcirculation of cirrhotic rats after lipopolysaccharide exposure. METHODS: Leukocyte rolling, adhesion and extravasation were visualized by intravital microscopy in sham-operated and common bile duct ligated (CBDL) rats. PegIFN alpha(2a) was administered to influence leukocyte recruitment. Endothelial P selectin, E-selectin and ICAM-1 expression were studied by immunohistochemistry. RESULTS: CBDL placebo rats showed significantly impaired rolling, adhesion and extravasation of leukocytes compared to Sham-operated placebo rats. Endothelial P selectin, E-selectin and ICAM-1 expressions in CBDL placebo rats were significantly reduced compared to Sham-operated placebo rats. PegIFN-alpha(2a) 18 microg normalized number of rolling leukocytes in CBDL rats, without influencing on adhering and extravasated leukocytes. PegIFN-alpha(2a) upregulates the expression of P-selectin and E-selectin in CBDL rats, but ICAM-1 expression remained significantly lower than in Sham rats. CONCLUSIONS: Leukocyte recruitment is significantly impaired in the mesenteric microcirculation of cirrhotic rats. This deficiency appears to result from a reduced endothelial P selectin, E-selectin and ICAM-1 expression. Peginterferon-alpha(2a) treatment normalizes rolling of leukocytes in cirrhotic rats by upregulation of P-selectin and E-selectin expressions, but has no influence on adhesion and extravasation possibly due to the absence of effect on ICAM-1 expression. PMID- 17275130 TI - Caenorhabditis evolution: if they all look alike, you aren't looking hard enough. AB - Caenorhabditis elegans is widely known as a model organism for cell, molecular, developmental and neural biology, but it is also being used for evolutionary studies. A recent meeting of researchers in Portugal covered topics as diverse as phylogenetics, genetic mapping of quantitative and qualitative intraspecific variation, evolutionary developmental biology and population genetics. Here, we summarize the main findings of the meeting, which marks the formal birth of a research community dedicated to Caenorhabditis species evolution. PMID- 17275129 TI - R-Etodolac decreases beta-catenin levels along with survival and proliferation of hepatoma cells. AB - BACKGROUND/AIMS: Inhibition of hepatoma cells by cyclooxygenase (COX)-2-dependent and -independent mechanisms has been shown previously. Here, we examine the effect of Celecoxib, a COX-2-inhibitor and R-Etodolac, an enantiomer of the nonsteroidal anti-inflammatory drug Etodolac, which lacks COX-inhibitory activity, on the Wnt/beta-catenin pathway and human hepatoma cells. METHODS: Hep3B and HepG2 cell lines were treated with Celecoxib or R-Etodolac, and examined for viability, DNA synthesis, Wnt/beta-catenin pathway components, and downstream target gene expression. RESULTS: Celecoxib at high doses affected beta catenin protein by inducing its degradation via GSK3beta and APC along with diminished tumor cell proliferation and survival. R-Etodolac at physiological doses caused decrease in total and activated beta-catenin protein secondary to decrease in its gene expression and post-translationally through GSK3beta activation. In addition, increased beta-catenin-E-cadherin was also observed at the membrane. An associated inhibition of beta-catenin-dependent Tcf reporter activity, decreased levels of downstream target gene products glutamine synthetase and cyclin-D1, and decreased proliferation and survival of hepatoma cells was evident. CONCLUSIONS: The antitumor effects of Celecoxib (at high concentrations) and R-Etodolac (at physiological doses) on HCC cells were accompanied by the down-regulation of beta-catenin demonstrating a useful therapeutic strategy in hepatocellular cancer. PMID- 17275131 TI - Plant centromere organization: a dynamic structure with conserved functions. AB - Although the structural features of centromeres from most multicellular eukaryotes remain to be characterized, recent analyses of the complete sequences of two centromeric regions of rice, together with data from Arabidopsis thaliana and maize, have illuminated the considerable size variation and sequence divergence of plant centromeres. Despite the severe suppression of meiotic chromosomal exchange in centromeric and pericentromeric regions of rice, the centromere core shows high rates of unequal homologous recombination in the absence of chromosomal exchange, resulting in frequent and extensive DNA rearrangement. Not only is the sequence of centromeric tandem and non-tandem repeats highly variable but also the copy number, spacing, order and orientation, providing ample natural variation as the basis for selection of superior centromere performance. This review article focuses on the structural and evolutionary dynamics of plant centromere organization and the potential molecular mechanisms responsible for the rapid changes of centromeric components. PMID- 17275132 TI - Reciprocal gene loss between Tetraodon and zebrafish after whole genome duplication in their ancestor. AB - The whole genome duplication that occurred in ray-finned fish coincided with the radiation of teleost species; consequently, these two phenomena have often been linked. Using the Tetraodon and zebrafish complete genome sequences, we tested a molecular hypothesis that can relate whole genome duplication to speciation in teleosts. We estimate that thousands of genes that remained duplicated when Tetraodon and zebrafish diverged underwent reciprocal loss subsequently in these two species, probably contributing to reproductive isolation between them. PMID- 17275134 TI - Robust measurement of ocular torsion using iterative Lucas-Kanade. AB - We present a new method to measure ocular torsion using Lucas-Kanade method. After pixels of iris annulus around a pupil have been converted into Cartesian coordinates, 30 features on the iris was selected then the features were tracked using the iterative Lucas-Kanade algorithm to calculate torsional shift. The results show that a precision of the method is higher than those measured by a conventional cross-correlation and by a template matching method. The suggested method showed 0.03 degrees mean error with 0.15 degrees maximum error. Particularly, the method was robust to change of pupil size and misalignment of pupil location. Processing time was also fast enough to be implemented in a real time system. PMID- 17275133 TI - The origins of multicellularity: a multi-taxon genome initiative. AB - The emergence of multicellular organisms from single-celled ancestors -- which occurred several times, independently in different branches of the eukaryotic tree -- is one of the most profound evolutionary transitions in the history of life. These events not only radically changed the course of life on Earth but also created new challenges, including the need for cooperation and communication between cells, and the division of labor among different cell types. However, the genetic changes that accompanied the several origins of multicellularity remain elusive. Recently, the National Human Genome Research Institute (NHGRI) endorsed a multi-taxon genome-sequencing initiative that aims to gain insights into how multicellularity first evolved. This initiative (which we have termed UNICORN) will generate extensive genomic data from some of the closest extant unicellular relatives of both animals and fungi. Here, we introduce this initiative and the biological questions that underpin it, summarize the rationale guiding the choice of organisms and discuss the anticipated benefits to the broader scientific community. PMID- 17275135 TI - An incremental neural network for tissue segmentation in ultrasound images. AB - This paper presents an incremental neural network (INeN) for the segmentation of tissues in ultrasound images. The performances of the INeN and the Kohonen network are investigated for ultrasound image segmentation. The elements of the feature vectors are individually formed by using discrete Fourier transform (DFT) and discrete cosine transform (DCT). The training set formed from blocks of 4x4 pixels (regions of interest, ROIs) on five different tissues designated by an expert is used for the training of the Kohonen network. The training set of the INeN is formed from randomly selected ROIs of 4x4 pixels in the image. Performances of both 2D-DFT and 2D-DCT are comparatively examined for the segmentation of ultrasound images. PMID- 17275136 TI - An efficient deconvolution algorithm for estimating oxygen consumption during muscle activities. AB - The reconstruction of an unknown input function from noisy measurements in a biological system is an ill-posed inverse problem. Any computational algorithm for its solution must use some kind of regularization technique to neutralize the disastrous effects of amplified noise components on the computed solution. In this paper, following a hierarchical Bayesian statistical inversion approach, we seek estimates for the input function and regularization parameter (hyperparameter) that maximize the posterior probability density function. We solve the maximization problem simultaneously for all unknowns, hyperparameter included, by a suitably chosen quasi-Newton method. The optimization approach is compared to the sampling-based Bayesian approach. We demonstrate the efficiency and robustness of the deconvolution algorithm by applying it to reconstructing the time courses of mitochondrial oxygen consumption during muscle state transitions (e.g., from resting state to contraction and recovery), from the simulated noisy output of oxygen concentration dynamics on the muscle surface. The model of oxygen transport and metabolism in skeletal muscle assumes an in vitro cylindrical structure of the muscle in which the oxygen from the surrounding oxygenated solution diffuses into the muscle and is then consumed by the muscle mitochondria. The algorithm can be applied to other deconvolution problems by suitably replacing the forward model of the system. PMID- 17275137 TI - The area composita of adhering junctions connecting heart muscle cells of vertebrates - III: assembly and disintegration of intercalated disks in rat cardiomyocytes growing in culture. AB - For cell and molecular biological studies of heart formation and function cell cultures of embryonal, neonatal or adult hearts of various vertebrates, notably rat and chicken, have been widely used. As the myocardium-specific cell-cell junctions, the intercalated disks (ID), have recently been found to be particularly sensitive to losses of - or mutations in - certain cytoskeletal proteins, resulting in cardiac damages, we have examined the ID organization in primary cultures of cardiomyocytes obtained from neonatal rats. Using immunofluorescence and immunoelectron microscopy, we have studied the major ID components for up to 2 weeks in culture, paying special attention to spontaneously beating, individual cardiomyocytes and myocardial cell colonies. While our results demonstrate the formation of some ID-like cardiomyocyte connecting junction arrays, they also reveal a variety of structural disorders such as rather extended, junction-free ID regions, sac-like invaginations and endocytotic blebs as well as accumulations of intracytoplasmic structures suggestive of endocytosed forms of junction-derived vesicles or of junction fragments resembling fascia adhaerens elements. Moreover, we have noticed a novel type of small, obviously plaque-free cytoplasmic vesicles containing one or both of the desmosomal cadherins, desmocollin Dsc2 and desmoglein Dsg2. We conclude that cardiomyocyte cultures are useful model systems for studies of certain aspects of myocardiac differentiation and functions but, on the other hand, show progressive disintegration and deterioration. The potential value of molecular markers and reagents in studies of myocardial pathology as well as in the monitoring of myocardial differentiation of so-called stem cells is discussed. PMID- 17275138 TI - A reliable, valid questionnaire indicates that preference for dietary fat declines when following a reduced-fat diet. AB - This study establishes the reliability and validity of the Fat Preference Questionnaire, a self-administered instrument to assess preference for dietary fat. Respondents select the food which tastes better and is eaten more frequently from 19 sets of food. Each set is comprised of related foods differing in fat content. The questionnaire was administered to women in laboratory-based (n=63), cross-sectional (n=150), and weight-loss (n=71) studies. The percentage of food sets in which high-fat foods were reported to "taste better" (TASTE score) and to be "eaten more often" (FREQ score) was determined. A measure of dietary fat restriction (DIFF) was created by subtracting TASTE from FREQ. Food intake was assessed by direct measure, 24-h recall, or food diary. Additionally, participants completed a standard survey assessing dietary restraint. Test-retest correlations were high (r=0.75-0.94). TASTE and FREQ scores were positively correlated with total fat intake (r=0.22-0.63). DIFF scores positively correlated with dietary restraint (r=0.39-0.52). Participants in the weight-loss trial experienced declines in fat consumption, TASTE and FREQ scores, and BMI values, and an increase in DIFF scores. Weight loss correlated with declines in FREQ (r=0.36) scores and increases in DIFF scores (r=-0.35). These data suggest that preference for dietary fat declines when following a reduced-fat diet and an increase in restraint for intake of dietary fat is important for weight loss. The Fat Preference Questionnaire is a stable, easily-administered instrument that can be used in research and clinical settings. PMID- 17275139 TI - Isolation, characterization and bioactivity of a region-specific pheromone, [Val8]sodefrin from the newt Cynops pyrrhogaster. AB - Previous analysis of PCR products derived from total RNA from the abdominal gland of the male newt, Cynops pyrrhogaster, inhabiting the Nara area of Japan led to the identification of a gene encoding [Val(8)]sodefrin, as well as the female attracting peptide pheromone, sodefrin. In this study, purification of this sodefrin variant from the abdominal glands of male newts from the Nara area was accomplished using gel-filtration chromatography and reversed-phase HPLC. Amino acid sequence analysis and mass spectrometry confirmed that the final product was [Val(8)]sodefrin. A full-length cDNA encoding the biosynthetic precursor of [Val(8)]sodefrin was cloned and characterized. The deduced amino acid sequence of prepro[Val(8)]sodefrin showed 86.2% identity with that of the sodefrin precursor. The [Val(8)]sodefrin variant potently attracted females from the Nara area, but the variant was much less or not effective in attracting females captured in the Niigata and Chiba areas. The term aonirin ("aoni" from "aoni-yoshi", the conventional epithet of Nara) is proposed to designate this region-specific pheromone. It is speculated that the coevolution of a novel pheromone and its complementary receptor in the Nara newts may lead to reproductive isolation and eventual differentiation into a separate species. PMID- 17275141 TI - Nutritional supplementation and dietary advice in geriatric patients at risk of malnutrition. AB - BACKGROUND & AIM: Effects of combined nutritional treatment of patients at risk of protein-energy malnutrition (PEM) discharged from a geriatric service were evaluated. METHODS: Patients (n=108, age 85+/-6 years) at risk of malnutrition according to the short form of the mini nutritional assessment were randomly allocated to dietary counseling, including liquid and multivitamin supplementation, i.e. intervention (I, n=51) and to controls (C, n=57). Body weight, biochemical indices (e.g. insulin-like growth factor I (IGF-I)), Katz activities of daily living (ADL) index, mini mental status examination (MMSE) and quality of life (QoL) by SF-36 were assessed at the start of the study and after 4 months. Statistical analyses were performed on "intention-to-treat" and on "treated-as-protocol" bases. RESULTS: Fifty-four patients, 29 in the I-group (86+/-7 years, 66% females) and 25 in the C-group (85+/-7 years, 72% females) completed the study according to the protocol. Both modes of analysis revealed a significant positive effect of the combined nutritional intervention on weight maintenance. Treated-as-protocol analyses showed that Katz ADL index improved in the I-group (p<0.001; p<0.05 between the groups). Serum IGF-I levels increased in the I-group (p<0.001), but were unchanged in the C-group (p=0.07 between the groups). QoL was assessed to be low and had not changed after nutritional treatment. CONCLUSIONS: Combined nutritional intervention prevented weight loss and improved ADL functions in discharged geriatric patients at risk of malnutrition. PMID- 17275140 TI - Mutant alpha-synuclein exacerbates age-related decrease of neurogenesis. AB - In Parkinson disease, wild-type alpha-synuclein accumulates during aging, whereas alpha-synuclein mutations lead to an early onset and accelerated course of the disease. The generation of new neurons is decreased in regions of neurogenesis in adult mice overexpressing wild-type human alpha-synuclein. We examined the subventricular zone/olfactory bulb neurogenesis in aged mice expressing either wild-type human or A53T mutant alpha-synuclein. Aging wild-type and mutant alpha synuclein-expressing animals generated significantly fewer new neurons than their non-transgenic littermates. This decreased neurogenesis was caused by a reduction in cell proliferation within the subventricular zone of mutant alpha-synuclein mice. In contrast, no difference was detected in mice overexpressing the wild type allele. Also, more TUNEL-positive profiles were detected in the subventricular zone, following mutant alpha-synuclein expression and in the olfactory bulb, following wild-type and mutant alpha-synuclein expression. The impaired neurogenesis in the olfactory bulb of different transgenic alpha synuclein mice during aging highlights the need to further explore the interplay between olfactory dysfunction and neurogenesis in Parkinson disease. PMID- 17275143 TI - Cross-priming by temozolomide enhances antitumor immunity of dendritic cell vaccination in murine brain tumor model. AB - Although chemotherapy remains among the best treatment options for most cancers, adjuvant therapies such as dendritic cell (DC)-based immunotherapy have been added to treatment protocols to destroy residual tumor cells. IFN-gamma secreting T cells specific for survivin was found after temozolomide (TMZ) treatment in C57BL/6 mice intracranial (i.c.) inoculated with GL26 cells. Furthermore, combination treatment with low-dose TMZ (2.5mg/kg/day, i.p.) chemotherapy followed by vaccination with survivin RNA-transfected DCs (1 x 10(6)cells/mouse, s.c.) enhanced T cells responses specific for survivin and improved survival rate compared with DC vaccination alone or TMZ treatment alone in tumor inoculated mice. However, these enhancements of T cells responses by TMZ treatment were not observed in mice without tumor inoculation. These results suggested that cross priming by TMZ may enhance antitumor immunity of DC vaccination in murine brain tumor model. PMID- 17275142 TI - Discovery of a vaccine antigen that protects mice from Chlamydia pneumoniae infection. AB - Chlamydiae are atypical intracellular bacteria that infect via mucosal surfaces causing, for example, trachoma, pneumonia, cervicitis, urethritis and infertility. Existing antibiotics are only partially effective and no vaccines are available. Using surface expressed or secreted proteins previously identified by genomics and proteomics we tested five as vaccines against intranasal challenge with Chlamydia pneumoniae. One antigen, LcrE, induced CD4+ and CD8+ T cell activation, type 1 cytokine secretion and neutralising antibodies and was completely effective in eliminating infection. Such antigens are highly conserved and essential to all Chlamydial species. The discovery of an effective vaccine for Chlamydiae pneumoniae has potential wide benefits for human health. PMID- 17275144 TI - Immunosenescence: role and measurement in influenza vaccine response among the elderly. AB - Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysfunction may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. Mounting biological evidence supports the potential clinical relevance and impact of immunosenenscence. We briefly review immunosenescence with a focus on replicative senescence in cytotoxic T cells and recent clinical studies examining its association with influenza and infectious disease outcomes. PMID- 17275145 TI - An experimental study of the biomechanical stability of ultrasound-activated pinned (SonicWeld Rx+Resorb-X) and screwed fixed (Resorb-X) resorbable materials for osteosynthesis in the treatment of simulated craniosynostosis in sheep. AB - We compared a conventional resorbable screw osteosynthesis with a resorbable, ultrasound-activated pin osteosynthesis, and studied mechanical load capacity and operative handling. This new form of osteosynthesis aims to reduce operation times, and to avoid torque loads and screw fractures to achieve stability. A sheep craniotomy model simulated an operation for dysmorphia on an infant skull. Two rectangular craniotomies of equal size were created in 13 lamb skulls, and each refixed by different means: the first by mesh and 20 screws, and the second by mesh with 20 pins inserted with ultrasound activation. All osteosynthesis material consisted of resorbable amorphous poly-(d,l)-lactide (PDLLA) (Resorb-X, KLS Martin, Tuttlingen, Germany). The insertion time was recorded. The animals were killed at different times, and areas of the healing skull including the plates and pins or screws were removed and divided into sections, which were then tested. In total 74 pin-fixed and 77 screw-fixed samples were obtained. Bending and tensile tests were used to simulate different forms of loading. The time required for the insertion of pins was significantly shorter than for screws. The mechanical tests showed differences in the stability of the bond between the osteosynthesis plate and bone that depended on the osteosynthesis system and the length of time it was in the animal. The pin osteosynthesis gave a stable mechanical load capacity, which was significantly different from that of screw osteosynthesis. Advantages of ultrasound-assisted, resorbable, pin osteosynthesis, include optimum operative handling, reduced insertion time, avoidance of fractures of the fixation elements and higher three-dimensional load capacity. PMID- 17275146 TI - A comparison of traditional practices used in pregnancy, labour and the postpartum period among women in Turkey and Iran. AB - OBJECTIVE: to examine and compare women's traditional practices regarding pregnancy, labour and the postpartum period. DESIGN: descriptive and comparative field research. SETTING: face-to-face interviews with women at home in Turkey and Iran. PARTICIPANTS: 300 women over 15 years of age from rural areas of Turkey (n=150) and Iran (n=150). FINDING: Turkey and Iran, two Middle Eastern countries, generally have similar traditional practices. It is surprising that some traditional practices are still used, although, in both countries, a number of contemporary practices have replaced them. Although some of the traditional practices, such as consuming low/high caloric food and herb drinks, may be harmless, others, such as jumping from a high place and pressing on the abdomen, may be completely harmful. Iranian women use traditional practices to reduce engorgement of the breast, and Turkish women use traditional practices to increase the amount of breast milk. Although traditional practices are less commonly used to reduce vaginal bleeding in both countries, they pose danger to the health of both mother and baby. CONCLUSIONS: various traditional practices about pregnancy, labour and the postpartum period take place in these two countries. Health professionals should be aware that pregnant women sometimes act on questionable advice concerning traditional practices. PMID- 17275147 TI - The rotational effect of pronation and supination osteotomies of the forearm in a cadaver model: a comparison of osteotomy sites on the radius and the ulna. AB - The purpose of this study was to investigate the effect on forearm rotation of rotation osteotomies at the distal and proximal levels of the radius and the ulna. Rotation osteotomies of 15 degrees and 30 degrees were made in the distal and proximal one-third of the radius and the ulna in ten cadaver specimens and changes of forearm arc of rotation were compared after osteotomy at the four sites. This study identifies the proximal ulna as the best of these sites for rotation osteotomy because of the high gain in the rotated direction and minimal loss in the opposite direction. PMID- 17275148 TI - A modification of the V-Y Moberg advancement flap for thumb reconstruction. PMID- 17275149 TI - Increased long-term failure risk associated with excessively thin cement mantle in cemented hip arthroplasty: a comparative in vitro study. AB - BACKGROUND: There is no consensus on possible detrimental effects of reduced thickness of the cement mantle surrounding hip stems. This work originated from the suspect that a successful design would yield inferior survival when implanted with a lower cement thickness. The scope was to assess with a reproducible in vitro experiment if a thinner cement mantle could cause a reduction of the long term implant fatigue resistance. METHODS: A comparative in vitro study was designed based on the same commercial stem (Centrament, Aesculap), implanted with the recommended (2-3mm) and reduced (1-2mm) cement thickness. Tests were carried out simulating 24 years of activity of active hip patients. A multifaceted approach was taken: inducible and permanent micromotions were recorded throughout the test; cement micro-cracks were quantified using dye-penetrants and statistically analyzed; crack surface and stem-cement fretting damage was investigate under Scanning Electron Microscopy. FINDINGS: The same stem, when implanted with a thinner cement mantle, tended to migrate significantly more (up to 0.3mm), with a tendency to loosen over time (increasing migration rate over time). After cyclic testing the cement mantle of the thinner specimens showed significantly more and longer cracks than the standard implants, with loose cement chips and signs of stem-cement fretting. INTERPRETATION: All these results confirmed that: (i) the stem under investigation had a good performance (in comparison with similar published work) when implanted with the recommended thickness; (ii) micromotion, cement cracking and fretting damage significantly increased when reduced cement mantle was used. Excessively thin cement mantle can result in critical conditions even for designs, which, in general, show low complications. PMID- 17275150 TI - Knee kinematics in functional activities seven years after total knee arthroplasty. AB - BACKGROUND: Detailed knowledge of knee kinematics during functional activities is lacking in current studies on the long-term outcome of total knee replacement surgery. The aim of this study was to assess functional knee kinematics using flexible electrogoniometry in patients seven years after unilateral primary total knee arthroplasty for osteoarthritis. METHODS: The knee joint functional movement of a cohort of patients (n=19) with knee osteoarthritis was assessed using electrogoniometry before surgery and 18-24 months and seven years after total knee surgery. The mean age of the patients (11 women and 8 men) at the time of the pre-surgery assessment was 67 years old (SD 8.0). Patient function was also assessed using the Knee Society Score and WOMAC osteoarthritis Index. FINDINGS: The function components of the Knee Society and WOMAC scores were significantly decreased at seven years compared to 18-24 months after surgery (both P<0.05). However, the majority of the functional knee flexion values derived from electrogoniometry did not decrease. Seven years after surgery, knee excursion during ascending and descending stairs was significantly improved compared to 18 24 months after surgery (both P<0.01). INTERPRETATION: The finding that functional knee motion continues to improve between 18-24 months and seven years post-surgery is of interest to both patients and those responsible for their treatment planning. Further, it was shown that the WOMAC and Knee Society Scores do not follow the same trends as the patients' functional knee kinematics seven years after total knee replacement surgery. PMID- 17275151 TI - Influence of changes in stem positioning on femoral loading after THR using a short-stemmed hip implant. AB - BACKGROUND: Short-stemmed hip implants were introduced to conserve proximal bone mass and may facilitate the use of minimally invasive surgery, in which smaller incisions limit access to the joint. This limited access may increase the risk of surgical mal-positioning of the implant, however the sensitivity of femoral loading to such mal-positioning of a short-stemmed implant has not been studied. METHODS: Finite element models were developed of a femur and a short-stemmed implant positioned to reproduce the intact hip centre, as well as with the implant placed in increased anteversion or offset. The effect of these surgical variables on femoral loading was examined for walking and stair climbing using loads from a validated musculoskeletal model. Results of the implanted models were compared with an intact model to evaluate stress shielding. FINDINGS: Implant position had little influence on cortical strains along the length of the diaphysis, although strains decreased by up to 95% at the neck resection level compared to the intact femur. In the proximal Gruen zones I and VII strain energy density among the implanted models varied by up to 0.4 kJ/m(3) (28%) and 0.6 kJ/m(3) (24%) under walking and stair climbing, respectively. All implanted models showed characteristic proximal stress shielding, indicated by a decrease in strain energy density of up to 5.4 kJ/m(3) (69%) compared to the intact femur. INTERPRETATION: Small changes in stem placement would likely have little influence on the internal loading of the femur after bone ingrowth has been achieved, however a reduction in strain energy density and therefore stress shielding was seen even for a short-stemmed implant, which may have consequences for longer-term bone remodelling. PMID- 17275152 TI - Assessing the impact of ambient ozone on growth and yield of a rice (Oryza sativa L.) and a wheat (Triticum aestivum L.) cultivar grown in the Yangtze Delta, China, using three rates of application of ethylenediurea (EDU). AB - Foliar applications of ethylenediurea (abbreviated as EDU) were made at 0, 150, 300 or 450 ppm to field-grown rice and wheat in the Yangtze Delta in China. Rice and wheat responded differently to ambient ozone and EDU applications. For wheat, some growth characteristics, such as yield, seed number per plant, seed set rate and harvest index, increased significantly at 300 ppm EDU treatment, while for rice no parameters measured were statistically different regarding EDU application. The reason may be that the wheat cultivar used may be more sensitive to ozone than the rice cultivar. EDU was effective in demonstrating ozone effects on the wheat cultivar, but not on the rice cultivar. Cultivar sensitivity might be an important consideration when assessing the effects of ambient ozone on plants. PMID- 17275153 TI - Promoting the O3 flux concept for European forest trees. AB - Tropospheric ozone (O3) levels are predicted to stay high, being a factor within "global change" with potential effects on the carbon sink strength of forest trees. Hence, new approaches to O3 risk assessment and their validation are required, although appropriate databases for adult trees are scant. Approaches based on external O3 exposure are presently being evaluated against the ones on O3 flux into leaves, as the cumulative uptake has the capacity for deriving O3 risk from cause-effect relationships. The effective dose, however, needs to account for the trees' O3 defence and tolerance in addition to O3 uptake. The current status of promoting the preferable mechanistic O3 flux concept is highlighted for major regions of Europe, addressing refinements and simplifications needed for routine use. At the pan-European scale, however, the flux-based concept is ready for use in O3 risk assessment and has the potential of meso-scale application at the forest ecosystem level. PMID- 17275155 TI - Post-rehabilitation environmental hazard of Cu, Zn, As and Pb at the derelict Conrad Mine, eastern Australia. AB - A post-rehabilitation audit of the derelict Conrad base metal mine, eastern Australia, indicates ongoing environmental hazard regarding acid mine drainage and concentrations of arsenic and lead to 3 wt% in the soil and sediment. In order to rehabilitate remote contaminated sites effectively, on-site analyses should be carried out to ensure that the materials used to rehabilitate the site are not contaminant-bearing. Understanding the geomorphic setting of the rehabilitated areas is also important in understanding where, and for what period, contaminated materials might be stored in fluvial systems downstream of mine workings. Chemical and geomorphic audits should form a fundamental part of all rehabilitation works to ensure favourable environmental outcomes. PMID- 17275154 TI - Effects of external phosphorus on the cell ultrastructure and the chlorophyll content of maize under cadmium and zinc stress. AB - Using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis, it was found that the ultrastructure of chloroplasts were changed, the shape of the chloroplasts altered and the numbers of grana that were asymmetrical increased; the numbers of grana and thylakoids decreased under the stress of Cd and Zn. The results indicated that the complex pollution involving Cd and Zn resulted in the membrane system of chloroplasts being damaged. When external phosphorus was applied, the numbers of damaged chloroplasts were significantly reduced and the nucleoli were better formed than those that did not receive phosphorus treatment. Moreover, many phosphate deposits were found in the vacuoles and on the surface of the roots, which were formed by phosphorus complexing with Cd (K(sp)=2.53x10(-33)) and Zn (K(sp)=9.00x10(-33)), respectively. Treatment with phosphorus conduced an increased chlorophyll content in plants compared with those that did not receive external phosphorus. PMID- 17275157 TI - Approaches in the risk assessment of genetically modified foods by the Hellenic Food Safety Authority. AB - Risk analysis has become important to assess conditions and take decisions on control procedures. In this context it is considered a prerequisite in the evaluation of GM food. Many consumers worldwide worry that food derived from genetically modified organisms (GMOs) may be unhealthy and hence regulations on GMO authorisations and labelling have become more stringent. Nowadays there is a higher demand for non-GM products and these products could be differentiated from GM products using the identity preservation system (IP) that could apply throughout the grain processing system. IP is the creation of a transparent communication system that encompasses HACCP, traceability and related systems in the supply chain. This process guarantees that certain characteristics of the lots of food (non-GM origin) are maintained "from farm to fork". This article examines the steps taken by the Hellenic Food Safety Authority to examine the presence of GMOs in foods. The whole integrated European legislation framework currently in place still needs to be implemented in Greece. Penalties should be enforced to those who import, process GMOs without special licence and do not label those products. Similar penalties should be enforced to those companies that issue false certificates beyond the liabilities taken by the food enterprises for farmers' compensation. We argue that Greece has no serious reasons to choose the use of GMOs due to the fact that the structural and pedologic characteristics of the Greek agriculture favour the biological and integrated cultivation more. Greece is not in favour of the politics behind coexistence of conventional and GM plants and objects to the use of GMOs in the food and the environment because the processor has a big burden in terms of money, time and will suffer a great deal in order to prove that their products are GMO free or that any contamination is adventitious or technically unavoidable. Moreover, Greece owns a large variety of genetic material that should try to protect from patenting and commercialisation. Finally, we should be aware of the requirements of movement of GMOs within borders, i.e. GMOs grown or used in other countries but which are not intended to cross into Greece, since Greece is very close to countries that are non-EU. This is where the development of a new, integrated, trustworthy and transparent food quality control system will help to satisfy the societal demands for safe and quality products. On the other hand, Greece should not be isolated from any recent scientific technological development and should assess the possible advantages for some cultivation using a case by case approach. Finally, the safety assessment of GM foods and feed has been discussed according to the risk assessment methodology applied by EFSA. PMID- 17275158 TI - An evaluation of objective feedback in basic life support (BLS) training. AB - BACKGROUND: Studies show that acquisition and retention of BLS skills is poor, and this may contribute to low survival from cardiac arrest. Feedback from instructors during BLS training is often lacking. This study investigates the effects of continuous feedback from a manikin on chest compression and ventilation techniques during training compared to instructor feedback alone. MATERIALS AND METHODS: A prospective randomised controlled trial. First-year healthcare students at the University of Birmingham were randomised to receive training in standard or feedback groups. The standard group were taught by an instructor using a conventional manikin. The feedback group used a 'Skillreporter' manikin, which provides continuous feedback on ventilation volume and chest compression depth and rate in addition to instructor feedback. Skill acquisition was tested immediately after training and 6 weeks later. RESULTS: Ninety-eight participants were recruited (conventional n=49; Skillreporter n=49) and were tested after training. Sixty-six students returned (Skillreporter n=34; conventional n=32) for testing 6 weeks later. The Skillreporter group achieved better compression depth (39.96mm versus 36.71mm, P<0.05), and more correct compressions (58.0% versus 40.4%, P<0.05) at initial testing. The Skillreporter group also achieved more correct compressions at week 6 (43.1% versus 26.5%, P<0.05). CONCLUSIONS: This study demonstrated that objective feedback during training improves the performance of BLS skills significantly when tested immediately after training and at re-testing 6 weeks later. However, CPR performance declined substantially over time in both groups. PMID- 17275156 TI - Evaluation of acute inhalation toxicity for chemicals with limited toxicity information. AB - A large reference database consisting of acute inhalation no-observed-adverse effect levels (NOAELs) and acute lethality data for 97 chemicals was compiled to investigate two methods to derive health-protective concentrations for chemicals with limited toxicity data for the evaluation of one-hour intermittent inhalation exposure. One method is to determine threshold of concern (TOC) concentrations for acute toxicity potency categories and the other is to determine NOAEL-to LC(50) ratios. In the TOC approach, 97 chemicals were classified based on the Globally Harmonized System of Classification and Labeling of Chemicals proposed by the United Nations into different acute toxicity categories (from most toxic to least toxic): Category 1, Category 2, Category 3, Category 4, and Category 5. The tenth percentile of the cumulative percentage distribution of NOAELs in each category was determined and divided by an uncertainty factor of 100 to derive the following health-protective TOC concentrations: 4microg/m(3) for chemicals classified in Category 1; 20microg/m(3) for Category 2; 125microg/m(3) for both Categories 3 and 4; and 1000microg/m(3) for Category 5. For the NOAEL-to-LC(50) ratio approach, 55 chemicals with NOAEL exposure durations < or = 24 hour were used to calculate NOAEL-to-LC(50) ratios. The tenth percentile of the cumulative percentage distribution of the ratios was calculated and divided by an uncertainty factor of 100 to produce a composite factor equal to 8.3x10(-5). For a chemical with limited toxicity information, this composite factor is multiplied by a 4-hour LC(50) value or other appropriate acute lethality data. Both approaches can be used to produce an estimate of a conservative threshold air concentration below which no appreciable risk to the general population would be expected to occur after a one-hour intermittent exposure. PMID- 17275159 TI - Biophysical and anthropogenic controls of forest fires in the Deccan Plateau, India. AB - Forest fires constitute one of the most serious environmental problems in several forested regions of India. In the Indian sub-continent, relatively few studies have focused on the assessment of biophysical and anthropogenic controls of forest fires at a landscape scale and the spatial aspects of these relationships. In this study, we used fire count data sets from satellite remote sensing data covering 78 districts over four different states of the Deccan Plateau, India, for assessing the underlying causes of fires. Spatial data for explanatory variables of fires pertaining to topography, vegetation, climate, anthropogenic and accessibility factors have been gathered corresponding with fire presence/absence. A logistic regression model was used to estimate the probability of the presence of fires as a function of the explanatory variables. Results for fire area estimates suggested that, of the total fires covering 47,043km(2) that occurred during the year 2000 for the entire Indian region, 29.0% occurred in the Deccan Plateau, with Andhra Pradesh having 13.5%, Karnataka 14.7%, Kerala 0.1%, and Tamilnadu 1.15%. Results from the logistic regression suggest that the strongest influences on the fire occurrences were the amount of forest area, biomass densities, rural population density (PD), average precipitation of the warmest quarter, elevation (ELE) and mean annual temperature (MAT). Among these variables, biomass density (BD) and average precipitation of the warmest quarter had the highest significance, followed by others. These results on the best predictors of forest fires can be used both as a strategic planning tool to address broad scale fire risk concerns, and also as a tactical guide to help forest managers to design fire mitigation measures at the district level. PMID- 17275160 TI - Goals and remedial strategies for water quality and wildlife management in a coastal lagoon--a case-study of Ringkobing Fjord, Denmark. AB - The aim of this work is (1) to discuss approaches and tools to set management goals using operational indicators for coastal management (i.e., indicators that are easy to measure, understand and predict) and validated predictive models and (2) to discuss remedial strategies for sustainable coastal management regarding water quality and the abundance of fish, waterfowl and large aquatic plants. These approaches are exemplified using data from Ringkobing Fjord, Denmark, which has undergone two major regime shifts during the last decades. This work discusses the changes taken place during the period from 1980 to 2004 (when there are good empirical data). For Ringkobing Fjord, which is a very shallow, well oxygenated lagoon dominated by resuspension processes, we have targeted on the following operational indicators, which are meant to reflect seasonal median values for the entire defined coastal area (the ecosystem scale) and not conditions at individual sites or data from shorter time periods: Secchi depth (as a standard measure of water clarity) and chlorophyll-a concentrations (as a key measure of algal biomass). The operational indicators are regulated by a set of standard abiotic factors, such as salinity, suspended particulate matter (SPM), nutrient concentrations (N and P), coastal morphometry and water exchange. Such relationships are quantified using well-tested, general quantitative models, which illustrate how these indicators are interrelated and how they reflect fundamental aspects of coastal ecosystems. We demonstrate that the regime shift in the lagoon can be modelled and quantitatively explained and is related to changes in salinity and nutrient inflow. A very important threshold is linked to increased salinities in the lagoon. For example, when the mean annual salinity is higher than about 9.5 per thousand, large numbers of saltwater species of clams can survive and influence the structure and function of the ecosystem in profound ways. The model also illustrates the dynamic response to changes in nutrient loading. We have presented several management strategies with the goal of keeping the Secchi depth at 2m, which would stimulate the growth of higher aquatic plants, which are fundamental for fish production and bird abundance in the lagoon. Given the fact that the Secchi depth depends on many variable factors (temperature, TP-inflow from land, salinity, changes in biomasses of macrophytes and clams, which are accounted for in these simulations), our results indicate that in practice it will likely be very difficult to reach that goal. However, it would be realistic to maintain a Secchi depth of 1.5m if the variability in salinity is minimized and the mean salinity is kept at about 10.2%. PMID- 17275161 TI - Valuing nature-based recreation in public natural areas of the Apalachicola River region, Florida. AB - As more people visit natural areas for tourism and recreation purposes, it is becoming increasingly important to understand the value they place on these natural resources. Specifically, tourists to Florida have been increasingly interested in visiting natural areas, forests, parks, and preserves-highlighting the importance of this new and growing phenomenon. We analyze visitors' demand for nature-based recreation in the Apalachicola River region of Florida using the travel cost method. The results from a count data regression model reveal that on average visitors would pay 74.18 dollars per visit-day for nature-based recreation resulting in a total economic value of 484.56 million dollars attributable to nature-based recreation in the Apalachicola River region. Results of this study provide useful information for natural resources management in the region and a rationale to preserve Florida's unique ecosystems. PMID- 17275162 TI - Analyzing the cost effectiveness of Santiago, Chile's policy of using urban forests to improve air quality. AB - Santiago, Chile has the distinction of having among the worst urban air pollution problems in Latin America. As part of an atmospheric pollution reduction plan, the Santiago Regional Metropolitan government defined an environmental policy goal of using urban forests to remove particulate matter less than 10 microm (PM(10)) in the Gran Santiago area. We used cost effectiveness, or the process of establishing costs and selecting least cost alternatives for obtaining a defined policy goal of PM(10) removal, to analyze this policy goal. For this study, we quantified PM(10) removal by Santiago's urban forests based on socioeconomic strata and using field and real-time pollution and climate data via a dry deposition urban forest effects model. Municipal urban forest management costs were estimated using management cost surveys and Chilean Ministry of Planning and Cooperation documents. Results indicate that managing municipal urban forests (trees, shrubs, and grass whose management is under the jurisdiction of Santiago's 36 municipalities) to remove PM(10) was a cost-effective policy for abating PM(10) based on criteria set by the World Bank. In addition, we compared the cost effectiveness of managing municipal urban forests and street trees to other control policies (e.g. alternative fuels) to abate PM(10) in Santiago and determined that municipal urban forest management efficiency was similar to these other air quality improvement measures. PMID- 17275163 TI - Synergy of interferon-alpha and 5-fluorouracil in human renal cell carcinoma requires p53 activity. AB - OBJECTIVES: Immunochemical therapy combining cytokines and chemotherapeutic agents is expected to be effective for treating advanced renal cell carcinoma (RCC). We investigated the mechanism underlying the synergism of interferon-alpha (IFN-alpha) and 5-fluorouracil (5-FU) and the effect of p53 status on the synergy of the combined therapy in RCC cell lines. METHODS: The synergy of IFN-alpha and 5-FU was analyzed by isobolographic analysis in five RCC cell lines. The effect of combined treatment on apoptosis induction was measured by flow cytometric analysis, Hoechst staining, and caspase activity assay; PCNA expression was investigated by Western blotting to examine the effect of combined treatment on the antiproliferative effect. RESULTS: We demonstrated synergy of IFN-alpha and 5 FU in five RCC cell lines with wild-type p53. IFN-alpha suppressed the proliferation of RCC cells via G1 or G2/M cell cycle arrest without inducing apoptosis, whereas 5-FU induced apoptosis in a dosage-dependent manner. IFN-alpha enhanced the apoptosis of RCC cells induced by 5-FU, whereas 5-FU did not increase the antiproliferative effect of IFN-alpha. However, the synergistic inhibition by IFN-alpha and 5-FU was abolished when the cell lines were transfected with p53 dominant-negative vector. CONCLUSIONS: The synergy of IFN alpha and 5-FU requires p53 activity, suggesting that p53 status may serve as a predictive factor for response to the combination therapy. Because metastatic RCC frequently has p53 mutations, therapy restoring p53 may markedly improve the response rate of immunochemical therapy combining IFN-alpha and 5-FU. PMID- 17275165 TI - Development and validation of a premature ejaculation diagnostic tool. AB - OBJECTIVES: Diagnosis of premature ejaculation (PE) for clinical trial purposes has typically relied on intravaginal ejaculation latency time (IELT) for entry, but this parameter does not capture the multidimensional nature of PE. Therefore, the aim was to develop a brief, multidimensional, psychometrically validated instrument for diagnosing PE status. METHODS: The questionnaire development involved three stages: (1) Five focus groups and six individual interviews were conducted to develop the content; (2) psychometric validation using three different groups of men; and (3) generation of a scoring system. For psychometric validation/scoring system development, data was collected from (1) men with PE based on clinician diagnosis, using DSM-IV-TR, who also had IELTs < or =2 min (n=292); (2) men self-reporting PE (n=309); and (3) men self-reporting no-PE (n=701). Standard psychometric analyses were conducted to produce the final questionnaire. Sensitivity/specificity analysis was used to determine an appropriate scoring system. RESULTS: The qualitative research identified 9 items to capture the essence of DSM-IV-TR PE classification. The psychometric validation resulted in a 5-item, unidimensional, measure, which captures the essence of DSM-IV-TR: control, frequency, minimal stimulation, distress, and interpersonal difficulty. Sensitivity/specificity analyses suggested a score of < or =8 indicated no-PE, 9 and 10 probable PE, and > or =11 PE. CONCLUSIONS: The development and validation of this new PE diagnostic tool has resulted in a new, user-friendly, and brief self-report questionnaire for use in clinical trials to diagnose PE. PMID- 17275166 TI - Editorial comment on: resurfacing and reconstruction of the glans penis. PMID- 17275167 TI - Molecular positron emission tomography and PET/CT imaging in urological malignancies. AB - OBJECTIVES: Positron emission tomography (PET) provides unique insights into molecular pathways of diseases. PET using [F-18]-fluorodeoxyglucose (FDG) has gained increasing acceptance for the diagnosis, staging, and treatment monitoring of various tumour types. The aim of this review is to provide an update on the current status of molecular PET and PET/CT imaging in urological malignancies. METHODS: The current literature on PET and PET/CT imaging was reviewed and summarized for prostate cancer, bladder cancer, renal cell carcinoma, and germ cell tumours. RESULTS: Depending on the radiotracer used, PET offers diagnostic information based on glucose, choline or amino acid metabolism and has also been applied to imaging tumour cell proliferation and tissue hypoxia in urological malignancies. The diagnostic performance of FDG-PET is hampered by the renal excretion of FDG and by the low metabolic activity often seen in tumours such as prostate cancer. However, new PET tracers including radiolabelled choline and acetate may offer an alternative approach. There is consistent evidence that FDG PET provides important diagnostic information in detecting metastatic and recurrent germ cell tumours and it might offer additional information in the staging and restaging of bladder and renal cancer. CONCLUSIONS: Although PET imaging has been shown to be a clinically useful tool, its application in urological malignancies still needs to be fully determined by larger prospective trials. The introduction of novel PET radiopharmaceuticals along with the new technology of PET/CT will likely change the future role of molecular imaging in urological malignancies. PMID- 17275169 TI - Resurfacing and reconstruction of the glans penis. AB - OBJECTIVES: To describe the techniques and results of surgical reconstruction of glans penis lesions. METHODS: Seventeen patients (mean age: 53.2 yr) were treated by resurfacing or reconstruction of the glans penis for benign, premalignant and malignant penile lesions. The aetiology of the lesions was one Zoon's balanitis, four lichen sclerosus, one carcinoma in situ, five squamous cell carcinomas, and six squamous cell carcinomas associated with lichen sclerosus. Five cases were treated by glans skinning and resurfacing; five cases by glans amputation and reconstruction of the neoglans, and seven cases by partial penile amputation and reconstruction of the neoglans. Glans resurfacing and reconstruction were performed with the use of a skin graft harvested from the thigh. RESULTS: The mean follow-up was 32 mo. All patients were free of local premalignant/malignant recurrence. Patients who underwent glans resurfacing reported glandular sensory restoration and complete sexual ability. Patients who underwent glansectomy or partial penectomy with neoglans reconstruction maintained sexual function and activity, although sensitivity was reduced as a consequence of glans/penile amputation. CONCLUSIONS: In selected cases of benign, premalignant or malignant penile lesions, glans resurfacing or reconstruction can ensure a normal appearing and functional penis, without jeopardizing cancer control. PMID- 17275170 TI - Design of accurate predictors for DNA-binding sites in proteins using hybrid SVM PSSM method. AB - In this paper, we investigate the design of accurate predictors for DNA-binding sites in proteins from amino acid sequences. As a result, we propose a hybrid method using support vector machine (SVM) in conjunction with evolutionary information of amino acid sequences in terms of their position-specific scoring matrices (PSSMs) for prediction of DNA-binding sites. Considering the numbers of binding and non-binding residues in proteins are significantly unequal, two additional weights as well as SVM parameters are analyzed and adopted to maximize net prediction (NP, an average of sensitivity and specificity) accuracy. To evaluate the generalization ability of the proposed method SVM-PSSM, a DNA binding dataset PDC-59 consisting of 59 protein chains with low sequence identity on each other is additionally established. The SVM-based method using the same six-fold cross-validation procedure and PSSM features has NP=80.15% for the training dataset PDNA-62 and NP=69.54% for the test dataset PDC-59, which are much better than the existing neural network-based method by increasing the NP values for training and test accuracies up to 13.45% and 16.53%, respectively. Simulation results reveal that SVM-PSSM performs well in predicting DNA-binding sites of novel proteins from amino acid sequences. PMID- 17275171 TI - Influence of the temporal distribution of electric pulses on transcallosal single unit responses. AB - We examined how differently timed stimuli to one auditory cortex affect the spike trains they drive in the controlateral homotopic field of anesthetized rats. Bipolar electrical stimulations consisted of trains of pulses (100 micro s, <500 micro A) at rates of 25, 50 or 125 pulses/s and with different stimulus patterns (i.e., dispersions, sequences), called "pacemaker", "accelerando" or "decelerando". Trains lasted for 342 ms and were separated by 4 s. When trains were evaluated over times comparable to the stimulus duration changes characteristically involved an initial slowing followed by recovery and several discharges both stimulus- and neuron-dependent. When evaluated by cross correlations between cortical cell pairs, the changes extended far beyond the stimulus end. Results suggest that interhemispheric projections, by way of their averages and patterns, play key, long duration roles in the spike-dependent properties of cortical synapses (e.g., potentiation, depression) and thus of cortical circuit operations. PMID- 17275172 TI - Coding the presence of visual objects in a recurrent neural network of visual cortex. AB - Before we can recognize a visual object, our visual system has to segregate it from its background. This requires a fast mechanism for establishing the presence and location of objects independently of their identity. Recently, border ownership neurons were recorded in monkey visual cortex which might be involved in this task [Zhou, H., Friedmann, H., von der Heydt, R., 2000. Coding of border ownership in monkey visual cortex. J. Neurosci. 20 (17), 6594-6611]. In order to explain the basic mechanisms required for fast coding of object presence, we have developed a neural network model of visual cortex consisting of three stages. Feed-forward and lateral connections support coding of Gestalt properties, including similarity, good continuation, and convexity. Neurons of the highest area respond to the presence of an object and encode its position, invariant of its form. Feedback connections to the lowest area facilitate orientation detectors activated by contours belonging to potential objects, and thus generate the experimentally observed border-ownership property. This feedback control acts fast and significantly improves the figure-ground segregation required for the consecutive task of object recognition. PMID- 17275173 TI - Inhomogeneous retino-cortical mapping is supported and stabilized with correlation-learning during self-motion. AB - In primates, the area of primary visual cortex representing a fixed area of visual space decreases with increasing eccentricity. We identify visual situations to which this inhomogeneous retino-cortical mapping is well adapted and study their relevance during natural vision and development. We assume that cortical activations caused by stationary objects during self-motion along the direction of gaze travel on average with constant speed across the cortical surface, independent of retinal eccentricity. This is the case if the distribution of objects corresponds to an ellipsoid with the observer in its center. We apply the resulting flow field to train a simple network of pulse coding neurons with Hebbian learning and demonstrate that the density of learned receptive field centers is in close agreement with primate retino-cortical magnification. In addition, the model reproduces the increase of receptive field size and the decrease of its peak sensitivity with increasing eccentricity. Our results suggest that self-motion may have played an important role in the evolution of the visual system and that cortical magnification can be refined and stabilized by Hebbian learning mechanisms in ontogenesis under natural viewing conditions. PMID- 17275174 TI - Minimally invasive biomarkers for detection and staging of colorectal cancer. AB - Colorectal cancer (CRC) is the third most prevalent cancer, with approximately one million cases estimated world wide in 2006, resulting in more than 500,000 deaths. Approximately 40% of colorectal cancers are diagnosed with localized disease, which have approximately a 90% five-year survival rate. However, the prognosis worsens with advancing stage, and only 5% of patients diagnosed with distant metastases survive 5 years. Therefore, the need for early detection is clear. Currently, guaiac-based fecal-occult blood testing (gFOBT) in large population-based trials has been shown to reduce CRC-related mortality, but the sensitivity for detecting early disease is low. DNA-based fecal screening appears to have the potential to significantly increase sensitivity without decreasing specificity. This review will focus primarily on newer molecular-based biomarkers and their utility in screening large populations for CRC, predicting treatment efficacy and providing prognostic information related to survival and disease progression. PMID- 17275175 TI - Catalytic therapy of cancer with porphyrins and ascorbate. AB - Catalytic therapy (CT) is a cancer treatment modality based on the generation of reactive oxygen species (ROS) using a combination of substrate molecules and a catalyst. The most frequently used substrate and catalyst pair is ascorbate/Co phthalocyanine (PcCo). In the present study, porphyrins containing transition metal ions as catalysts in place of PcCo were studied. Porphyrins that are expected to be as efficient as phthalocyanines, but may have fewer side effects, were analyzed. ROS production through the combined use of ascorbate and porphyrins decreased the number of breast cancer tumor cells by 20-40% after a single in vitro treatment, as compared to control cells. Treatment with ascorbate in conjunction with porphyrins stimulated apoptosis and disrupted the cell cycle. These treatments enhanced apoptosis by 20-40% when compared to treatments with ascorbate and porphyrins. In addition, the number of cells accumulating in the sub G0/G1 stage of the cell cycle increased from 3- to 10-fold, potentially reflecting that the treatment was highly effective in inducing DNA damage in the tumor cells, suggesting that porphyrins may be beneficial as a CT catalyst in the treatment of cancer. PMID- 17275176 TI - Co-repression of mismatch repair gene expression by hypoxia in cancer cells: role of the Myc/Max network. AB - The key microenvironmental stress of hypoxia is associated with a diverse spectrum of alterations in both the expression and activation patterns of numerous DNA repair and stress-response factors. We have shown previously that hypoxia causes decreased expression of the mismatch repair gene, MLH1, leading to increased genetic instability in tumor cells, although the mechanism remained to be determined. Here we elucidate a mechanism by which MLH1 and another mismatch repair (MMR) gene, MSH2, are repressed by hypoxia. This repression occurs via a dynamic shift in occupancy from activating c-Myc/Max to repressive Mad1/Max and Mnt/Max complexes at the proximal promoters of both the MLH1 and MSH2 genes. Repression of the MMR genes was also seen in both hypoxia-inducible factor (HIF) proficient and deficient cells, and so ruling out an essential role for HIFs in MMR gene expression. These data highlight a novel HIF-independent stress-response pathway induced by hypoxia leading to the coordinated repression of MLH1 and MSH2, key genes in the MMR pathway, and they provide further insight into the possible mechanisms of hypoxia-induced genetic instability and consequent tumor progression in cancer cells. PMID- 17275178 TI - Oncopeptidomics--a commentary on opportunities and limitations. AB - Cancer cells exhibit specific changes in protein expression and alterations in proteolytic activities. Peptides are capable of reflecting these pathological changes and are educible by dedicated analytical technologies. Oncopeptidomics can be defined as the comprehensive multiplexed analysis of endogenous peptides from a biological sample, under defined conditions, to discover probable valid peptide tumor biomarker. Here, mass spectrometry has shown its potential as a comprehensive peptide profiling tool. The efforts to arrive at diagnostically relevant biomarkers may have been underestimated. The establishment of novel cancer biomarkers will necessitate a multidisciplinary effort and presumably require a duration comparable to the drug development process. This review will address current concepts, new perspectives and the developmental process leading to clinically useful peptide tumor markers. PMID- 17275177 TI - Survivin: a promising tumor biomarker. AB - Survivin is a 16.5 kDa protein overexpressed in almost all malignancies but rarely detected in normal differentiated adult tissues. Functionally, survivin has been shown to inhibit apoptosis, promote cell proliferation and enhance angiogenesis. Consistent with its role in these processes, survivin has been shown to play a key role in cancer progression. Because of the large difference in expression between normal and malignant tissue and its causal role in cancer progression, survivin is currently undergoing intensive investigation as a potential tumor marker. Emerging data suggests that measurement of survivin can aid the early diagnosis of bladder cancer, determine prognosis in multiple cancer types and predict response to diverse anti-cancer therapies. These preliminary findings on the diagnostic, prognostic and predictive potential of survivin should now be confirmed in large prospective trials. Furthermore, assays for the measurement of survivin should be simplified, standardized and evaluated in external quality assurance schemes. PMID- 17275179 TI - Human tissue kallikreins: the cancer biomarker family. AB - Human tissue kallikreins (KLKs) are attracting increased attention due to their role as biomarkers for the screening, diagnosis, prognosis, and monitoring of various cancers including those of the prostate, ovarian, breast, testicular, and lung. Human tissue kallikrein genes represent the largest contiguous group of proteases within the human genome. Originally thought to consist of three genes, the identification of the human kallikrein locus has expanded this number to fifteen. These genes, and their encoded proteins, share a high degree of homology and are expressed in different tissues. Prostate-specific antigen (PSA), the most commonly known kallikrein, is a useful biomarker for prostate cancer. Several other kallikreins, including kallikreins 2 (KLK2) and 11 (KLK11) are emerging as complementary prostate cancer biomarkers. Along with these kallikreins, several others have been implicated in the other cancers. For example, KLK5, 6, 7, 10, 11, and 14 are emerging biomarkers for ovarian cancer. The identification of kallikrein substrates and the development of proteolytic cascade models implicate kallikrein proteins in cancer progression. This review describes the current status of kallikreins as cancer biomarkers. PMID- 17275180 TI - The role of membrane transporters in drug delivery to brain tumors. AB - Most brain tumors are highly resistant to chemotherapy because many chemotherapeutic drugs poorly cross the blood-brain barrier, the blood cerebrospinal-fluid barrier, and the plasma membrane of the tumor cells. This restricted drug delivery is largely due to the presence of integral plasma membrane proteins belonging to the solute carriers (SLCs) and to the ATP-binding cassette (ABC) superfamily of transporters that decisively determine substance uptake and efflux, respectively, by the barrier-forming cells and the tumor cells. This review focuses on the localization and function of drug-transporting members of both transporter groups in human brain. PMID- 17275181 TI - Removal of some heavy metals by CKD leachate. AB - In this study, Cu(II), Ni(II), and Zn(II) ions were precipitated from synthetic aqueous solutions as hydroxides by using CKD leachate. Precipitation tests were carried out batch wise in agitated flasks with single-metal solutions (each solution contained 100 mg/l of one of the three metals), and a multi-metal solution that contained 50 mg/l of each of the three elements. The results showed that high removal efficiencies, approaching 100%, of these heavy metals were attained and the leachate of the solid waste CKD, therefore, can be used for removing heavy metals from aqueous solutions. PMID- 17275182 TI - Soil dioxins levels at agriculture sites and natural preserve areas of Taiwan. AB - In this study, agriculture soil in Taiwan has been sampled and analyzed to determine the background level of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DF) in the agricultural and nature preserve areas. Another objective is to investigate relationship between soil characteristics and air deposition in Taiwan. The results indicate that in nature preserve areas the topsoil shows an extraordinary profile of PCDD/DF compared to that in the air deposition. The PCDD/DF levels of the low-contaminated agricultural soils are compatible with those of the nature preserves soils. However, in the highly contaminated agricultural soils, there is an abrupt jump in their concentrations, 10-100 times higher. The overall I-TEQ values of the background topsoils range from 0.101 to 15.2 ng I-TEQ/kg. Near industrial/urban areas in Taiwan the PCDD/DF are slightly higher compared to those in the low concentration group. Typically, the PCDD/DF background values found in this survey fall in the 90% confidence interval and can thus, be deemed the background levels in Taiwan. Ninety-five percent of these data are below the European and American soil standard of 10 ng I-TEQ/kg d.w. The PCDD/DF profile with one neighborhood soil sample was shown no significant difference. PMID- 17275183 TI - Adsorptive removal of phthalate ester (Di-ethyl phthalate) from aqueous phase by activated carbon: a kinetic study. AB - Adsorptive studies were carried out on Di-ethyl phthalate (DEP) removal from aqueous phase onto activated carbon. Batch sorption studies were performed and the results revealed that activated carbon demonstrated ability to adsorb DEP. Influence of varying experimental conditions such as DEP concentration, pH of aqueous solution, and dosage of adsorbent were investigated on the adsorption process. Sorption interaction of DEP onto activated carbon obeyed the pseudo second order rate equation. Experimental data showed good fit with both the Langmuir and Freundlich adsorption isotherm models. DEP sorption was found to be dependent on the aqueous phase pH and the uptake was observed to be greater at acidic pH. PMID- 17275184 TI - Long-term treatment issues with chromite ore processing residue (COPR): Cr(6+) reduction and heave. AB - A pugmill treatability study was conducted to remediate chromite ore processing residue (COPR) using ferrous sulfate heptahydrate (FeSO(4) x 7H(2)O) as a reductant. Two different types of COPR, with respect to particle size and mineralogy, were tested in this study. Two different stoichiometric ratios of FeSO(4) x 7H(2)O to Cr(6+) (5x and 8x) were applied to reduce Cr(6+) to Cr(3+). The effectiveness of FeSO(4).7H(2)O treatment was assessed using the toxicity characteristic leaching procedure (TCLP) tests and X-ray absorption near edge structure (XANES) analyses. TCLP results obtained from the pugmill treatability study showed that TCLP Cr concentrations were less than the TCLP regulatory limit of 5mg/L upon 8x FeSO(4) x 7H(2)O treatment for up to 420 days but may fail to meet this regulatory limit in the long-term. XANES results obtained from samples cured for 300 days showed that all of the treated samples failed the New Jersey Department of Environmental Protection (NJDEP) clean up level for Cr(6+) of 240 mg/kg. However, the Cr(6+) concentration from the sample with the smaller particle size approached 240 mg/kg (338 mg/kg), suggesting that particle size reduction prior to the addition of reductant may improve the effectiveness of the treatment. COPR heaving was investigated with unconfined swell tests upon 5x and 8x FeSO(4) x 7H(2)O treatment. The formation of ettringite, an expansive material, was investigated following the swell tests using X-ray powder diffraction (XRPD). Significant heaving (>50 vol%) was observed at curing times of 138 days for the 5x treatment and the ettringite formation was identified by XRPD analyses. PMID- 17275185 TI - Bioleaching of chromium from tannery sludge by indigenous Acidithiobacillus thiooxidans. AB - Chromium in tannery sludge will cause serious environmental problems and is toxic to organisms. The acidophilic sulfur-oxidizing Acidithiobacillus thiooxidans can leach heavy metals form urban and industrial wastes. This study examined the ability of an indigenous sulfur-oxidizing A. thiooxidans to leach chromium from tannery sludge. The results showed that the pH of sludge mixture inoculated with the indigenous A. thiooxidans decreased to around 2.0 after 4 days. After 6 days incubation in shaking flasks at 30 degrees C and 160 rpm, up to 99% of chromium was solubilized from tannery sludge. When treated in a 2-l bubble column bioreactor for 5 days at 30 degrees C and aeration of 0.5 vvm, 99.7% of chromium was leached from tannery sludge. The results demonstrated that chromium in tannery sludge can be efficiently leached by the indigenous A. thiooxidans. PMID- 17275186 TI - Biological and chemical removal of Cr(VI) from waste water: cost and benefit analysis. AB - The objective of the present study is cost and benefit analysis of biological and chemical removal of hexavalent chromium [Cr(VI)] ions. Cost and benefit analysis were done with refer to two separate studies on removal of Cr(VI), one of heavy metals with a crucial role concerning increase in environmental pollution and disturbance of ecological balance, through biological adsorption and chemical ion exchange. Methods of biological and chemical removal were compared with regard to their cost and percentage in chrome removal. According to the result of the comparison, cost per unit in chemical removal was calculated 0.24 euros and the ratio of chrome removal was 99.68%, whereas those of biological removal were 0.14 and 59.3% euros. Therefore, it was seen that cost per unit in chemical removal and chrome removal ratio were higher than those of biological removal method. In the current study where chrome removal is seen as immeasurable benefit in terms of human health and the environment, percentages of chrome removal were taken as measurable benefit and cost per unit of the chemicals as measurable cost. PMID- 17275187 TI - Correlation in Lewy pathology between the claustrum and visual areas in brains of dementia with Lewy bodies. AB - We investigated Lewy pathologies in the claustrum and the related cerebral cortices and subcortical nuclei of dementia with Lewy bodies (DLB) brains using alpha-synuclein-immunohistochemistry to clarify the relationship between Lewy pathology in the claustrum and visual misidentification of DLB patients. The claustrum is known to have strong reciprocal connections with the visual areas. Consequently, the claustrum demonstrated many Lewy bodies (LB) and LB-related neurites. The insular and inferior temporal cortices, amygdala, BA 18, 19, transentohrinal and cingulate cortices showed stronger or similar Lewy pathology as compared with the claustrum, while BA 17, precentral, postcentral and transverse temporal cortices showed weaker Lewy pathology. Comparing the correlation coefficient of Lewy pathology between the clausturm and other regions, BA 18 and 19 as well as the insular and transentorhinal cortices demonstrated a higher correlation coefficient. These findings suggest that Lewy pathology in the claustrum is more closely associated with that in visual areas than in auditory, somatosensory or motor areas, and that dysfunction of the visuo claustral pathway participates in visual misidentification in addition to the visuo-amygdaloid pathway. The paralimbic cortices including the insular and transentorhinal cortices may connect visual areas with limbic areas by relay of the visuo-claustral or visuo-amygdaloid pathway. PMID- 17275188 TI - Differential expression of glial cell line-derived neurotrophic factor family receptor alpha-2 isoforms in rat urinary bladder and intestine. AB - Neurturin (NTN) is a member of the glial cell line-derived (GDNF) family of neurotrophic factors, which act via a receptor complex composed of a signal transducing receptor, c-Ret and a glycosylphosphatidylinositol (GPI)-linked ligand binding receptor, GFRalpha. Different members of the GDNF family bind preferentially to one of four different GFRalpha receptors; NTN binds preferentially to the GFRalpha-2 receptor. Recent evidence has shown that three alternatively spliced isoforms of GFRalpha-2 occur in rodent tissues, including the rat brain, myenteric plexus and kidney, and several mouse tissues. Here we have examined the occurrence of GFRalpha-2 isoforms in the adult male rat urinary bladder by RT-PCR, in parallel with samples from the muscularis externa of the rat ileum. In contrast to the ileum, only a single GFRalpha-2 isoform, the smallest isoform, known as GFRalpha-2c, was detected in the rat urinary bladder. This differential expression of GFRalpha-2 transcripts in bladder and intestine may be related to differences in the roles of NTN in the two tissues and its actions on the neurons that innervate them. PMID- 17275189 TI - Neurosteroid modulation of GABAergic neurotransmission in the central amygdala: a role for NMDA receptors. AB - The neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone or ALLO) positively modulates GABA(A) receptors, an action that may contribute to the anxiolytic effects of ALLO. Recent evidence suggests that ALLO's anxiolytic effects appear to be mediated by the amygdala, a key neural structure for emotional and cognitive behaviors. However, little is known regarding ALLO effects on amygdala physiology. We therefore explored ALLO effects on GABA neurotransmission in the central nucleus (Ce) of the amygdala, a major output nucleus involved in fear and anxiety. We recorded evoked GABA(A) receptor mediated inhibitory postsynaptic currents (IPSCs) in Ce neurons using whole-cell patch clamp techniques. We observed that ALLO significantly reduced the amplitude of evoked GABA(A) receptor-mediated IPSCs. However, the effect of ALLO was occluded by the NMDA receptor antagonist D-APV. D-APV alone also reduced evoked IPSCs in Ce neurons. These results suggest that ALLO-induced reduction of GABAergic transmission in Ce appears to depend on neural network activity, possibly involving an NMDA receptor-mediated mechanism. These ALLO effects on GABAergic transmission in the central amygdala may play a role in mediating its anxiolytic actions. PMID- 17275191 TI - Progress in the development of Fasciola hepatica vaccine using recombinant fatty acid binding protein with the adjuvant adaptation system ADAD. AB - Fatty acid binding proteins (FABP) have been designed as a potential vaccine against fasciolosis. In this work, the immunoprophylaxis of the recombinant Fh15 FABP from F. hepatica (Fh15) in adjuvant/immunomodulator ADAD system was evaluated using mice and sheep challenged with F. hepatica. The ADAD system combines the Fh15 antigen with an immunomodulator (hydroalcoholic extract of Polypodium leucotomos; PAL) and/or an adjuvant (saponins of Quillaja saponaria; Qs) in a water/oil emulsion (30/70) with a non-mineral oil (Montanide). All the infected control mice died by 41-48 days post-infection. The mice vaccinated with ADAD only with PAL+Fh15 present a survival rate of 40-50% and those vaccinated with ADAD containing PAL+Qs+Fh15 had a survival rate of 50-62.5%. IgG1 antibodies were lower in surviving mice in comparison with non-surviving mice. The sheep vaccinated with ADAD PAL+Qs+Fh15 showed lower fluke recovery (43%), less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Thus, the ADAD system using recombinant fatty acid binding proteins from F. hepatica could be a good option to develop vaccines against F. hepatica. PMID- 17275192 TI - Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma. AB - Primary cutaneous T-cell lymphomas are a heterogenous group of non-Hodgkin lymphomas. The characteristic clinicopathologic and immunophenotypic features and prognoses of the various cutaneous lymphomas have been recently described by the World Health Organization and European Organization for Research and Treatment of Cancer. Cutaneous T-cell lymphoma variants include mycosis fungoides and Sezary syndrome, which are generally associated, respectively, with indolent and aggressive clinical courses and are the subject of this review. Currently utilized treatments for cutaneous T-cell lymphoma include skin-directed therapies (topical agents such as corticosteroids, mechlorethamine, carmustine, and retinoids, phototherapy, superficial radiotherapy, and total skin electron beam therapy), systemic therapies (photophoresis, retinoids, denileukin diftitox, interferons, and chemotherapy), and stem cell transplantation (autologous and allogeneic). This review will describe recent advances in our understanding of the biology (immunologic, cytogenetic, and genetic) of cutaneous T-cell lymphomas and discuss the efficacy and tolerability of the current therapeutic options for cutaneous T-cell lymphomas. Disease progression in over 20% of patients with early stages of disease and the current lack of a definitive treatment which produces durable responses in advanced stages of disease indicates a critical unmet need in CTCL. New insights into the molecular and immunologic changes associated with cutaneous T-cell lymphomas should ultimately lead to the identification of novel therapeutic targets and the development of improved therapeutic options for patients with these malignancies. PMID- 17275190 TI - Mechanisms of expression of apoptotic protease activating factor-1 (Apaf-1) in nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets. AB - Apoptotic protease activating factor-1 (Apaf-1) is a critical regulator of apoptosis and a crucial part of the apoptosome that is assembled in response to several cellular stresses like hypoxia. We have previously shown that hypoxia results in increased influx of nuclear Ca(2+) and increased expression of nuclear apoptotic proteins. The present study investigates that Apaf-1 is expressed during hypoxia in the cerebral cortex of newborn piglets and that administration of clonidine prevents the hypoxia induced increase expression of Apaf-1. Studies were conducted in 19 newborn piglets, 6 normoxic (Nx), 7 hypoxic (Hx FiO(2) of 0.05-0.07 for 1h) and 6 clonidine-treated hypoxic (Hx-Clo) piglets. Tissue hypoxia was confirmed biochemically by determining the levels of high energy phosphates ATP and phosphocreatine (PCr). Neuronal nuclei, mitochondrial membranes and cytosolic fractions were isolated and separated by 12% SDS-PAGE and probed with specific antibodies to Apaf-1. The expression of Apaf-1 in neuronal nuclei was 48.86+/-5.27 in Nx, 108.43+/-6.37 in Hx and 78.53+/-7.00 in Hx-Clo. The Apaf-1 expression of in mitochondrial fraction was 72.73+/-11.76 in Nx, 132.27+/-16.15 in Hx and 85.17+/-5.64 in Hx-Clo. Similarly, the expression of Apaf-1 in cytosolic fraction was 86.79+/-6.97 in Nx, 193.95+/-15.41 in Hx and 111.07+/-7.91 in Hx-Clo. In summary, the results show that hypoxia results in increased expression of Apaf-1 proteins in neuronal nuclear, mitochondrial and cytosolic fractions. Administration of a high affinity Ca(2+)-ATPase, prevented the hypoxia induced increased expression of Apaf-1 protein, suggesting that the hypoxia-induced increased expression of Apaf-1 proteins is nuclear Ca(2+)-influx mediated. We conclude that cerebral hypoxia-induced increase in Apaf-1 protein will lead to increased activation of procaspase-9 to caspase-9 in the cytosolic compartment leading to a cascade of hypoxic neuronal death. PMID- 17275193 TI - Involvement of prostaglandin E(2) derived from enteric glial cells in the action of bradykinin in cultured rat myenteric neurons. AB - We characterized bradykinin (BK)-induced changes in the intracellular Ca(2+) concentration ([Ca(2+)]i) and membrane potential in cultured rat myenteric neurons using ratiometric Ca(2+) imaging with fura-2 and the whole-cell patch clamp technique, respectively. BK evoked a dose-dependent increase of [Ca(2+)]i that was abolished by HOE 140, a B2 receptor antagonist but not by [Lys-des Arg(9)]-BK, a B1 receptor antagonist. [Lys-des-Arg(9)]-HOE140, a B1 receptor agonist, failed to cause a [Ca(2+)]i response. Double staining with antibodies against the B2 receptor together with PGP9.5 or S100 indicated that B2 receptors were expressed in neurons and glial cells. The BK-evoked [Ca(2+)]i increase was suppressed by indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and potentiated by prostaglandin E(2) (PGE(2)). The release of PGE(2) from cultured myenteric plexus cells was increased by BK. BK induced a large increase in [Ca(2+)]i in neurons when myenteric plexus cells were cultured at the high density but not at the low density, and caused a small increase in [Ca(2+)]i in neurons when proliferation of enteric glial cells was suppressed. BK evoked a slow and sustained depolarization in myenteric neurons, which was sensitive to indomethacin. These results indicated that BK caused a [Ca(2+)]i increase and depolarization in rat myenteric neurons through the activation of B2 receptors, which was partly associated with PGE(2) released from glial cells in response to BK. It is suggested that a neuron-glial interaction plays an important role in the effect of BK in the rat myenteric plexus. PMID- 17275194 TI - Tinnitus behavior and hearing function correlate with the reciprocal expression patterns of BDNF and Arg3.1/arc in auditory neurons following acoustic trauma. AB - The molecular changes following sensory trauma and the subsequent response of the CNS are poorly understood. We focused on finding a molecular tool for monitoring the features of excitability which occur following acoustic trauma to the auditory system. Of particular interest are genes that alter their expression pattern during activity-induced changes in synaptic efficacy and plasticity. The expression of brain-derived neurotrophic factor (BDNF), the activity-dependent cytoskeletal protein (Arg3.1/arc), and the immediate early gene c-Fos were monitored in the peripheral and central auditory system hours and days following a traumatic acoustic stimulus that induced not only hearing loss but also phantom auditory perception (tinnitus), as shown in rodent animal behavior models. A reciprocal responsiveness of activity-dependent genes became evident between the periphery and the primary auditory cortex (AI): as c-Fos and BDNF exon IV expression was increased in spiral ganglion neurons, Arg3.1/arc and (later on) BDNF exon IV expression was reduced in AI. In line with studies indicating increased spontaneous spike activity at the level of the inferior colliculus (IC), an increase in BDNF and GABA-positive neurons was seen in the IC. The data clearly indicate the usefulness of Arg3.1/arc and BDNF for monitoring trauma induced activity changes and the associated putative plasticity responses in the auditory system. PMID- 17275195 TI - Maternal deprivation and early handling affect density of calcium binding protein containing neurons in selected brain regions and emotional behavior in periadolescent rats. AB - Adverse early life experiences can induce neurochemical changes that may underlie modifications in hypothalamic-pituitary-adrenal axis responsiveness, emotionality and cognition. Here, we investigated the expression of the calcium binding proteins (CBPs) calretinin, calbindin and parvalbumin, which identify subpopulations of GABAergic neurons and serve important functional roles by buffering intracellular calcium levels, following brief (early handling) and long (maternal deprivation) periods of maternal separation, as compared with non handled controls. CBP-expressing neurons were analyzed in brain regions related to stress and anxiety. Emotionality was assessed in parallel using the social interaction test. Analyses were carried out at periadolescence, an important phase for the development of brain areas involved in stress responses. Our results indicate that density of CBP-immunoreactive neurons decreases in the paraventricular region of deprived rats but increases in the hippocampus and lateral amygdala of both early-handled and deprived rats when compared with controls. Emotionality is reduced in both early-handled and deprived animals. In conclusion, early handling and deprivation led to neurochemical and behavioral changes linked to stress-sensitive brain regions. These data suggest that the effects of early experiences on CBP containing neurons might contribute to the functional changes of neuronal circuits involved in emotional response. PMID- 17275197 TI - The effect glucocorticoids on aggressiveness in established colonies of rats. AB - It was repeatedly shown that glucocorticoids increase aggressiveness when subjects are socially challenged. However, the interaction between challenge exposure and glucocorticoid effects was not investigated yet. We studied this interaction by assessing the effects of glucocorticoids in established colonies of rats, i.e. in rats that were not exposed to an acute social challenge. Aggressiveness was high immediately after colony formation but decreased sharply within 4 days and remained stable thereafter. Mild dominance relations were observed in 11 colonies (65%). Approximately three weeks after colony formation, rats remained undisturbed or were injected with vehicle or corticosterone. Routine colony life was followed for 1h after treatments. Injections per se induced a mild and transient behavioral activation: resting was reduced, whereas exploration, social and agonistic interactions were increased. The change lasted about 15min. Corticosterone--although plasma corticosterone levels were increased -had no specific effect, as the behavior of vehicle- and corticosterone-treated rats was similar. Social rank had a minor impact on the results. In contrast, the pro-aggressive effects of corticosterone were robust under conditions of social challenge and were maintained after repeated exposure to aggressive encounters. It occurs that an acute increase in glucocorticoids promotes social challenge induced aggressiveness, but does not increase aggressiveness under routine conditions. We hypothesize that the pro-aggressive effects of glucocorticoids develop in conjunction with challenge-induced neuronal (e.g. monoaminergic) activation. PMID- 17275196 TI - Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. AB - Synuclein was initially named for its localization in both presynaptic nerve terminals and portions of nuclear envelope. However, subsequent studies only confirmed the presynaptic localization of this protein in the brain; its nuclear localization in the neurons remained elusive. Here, two new monoclonal antibodies against alpha-synuclein (alpha-SYN) were produced. Epitope mapping using phage peptide display showed that the epitopes of the two antibodies were localized in two distinct specific sequences of the C-terminal domain of alpha-SYN. One antibody named 3D5 recognized amino acids 115-121 of alpha-SYN and the other antibody named 2E3 identified the amino acids 134-138 of the protein. Western blot analysis demonstrated that both 2E3 and 3D5 detected a 19 kD protein from rat and human brain homogenates, which was identical to the molecular size of recombinant alpha-SYN. However, immunohistochemical staining on normal adult rat brain sections showed that the two antibodies revealed distinct patterns of subcellular localization of alpha-SYN immunoreactivity. Both 3D5 and 2E3 detected the presynaptic alpha-SYN but only 3D5 detected the nuclear alpha-SYN. The nuclear localization of alpha-SYN was further confirmed by Western blot analysis in isolated nuclear fraction where the same size of alpha-SYN was detected, and by immunoelectron microscopy using colloidal gold probes where gold particles were specifically localized in portions of peri- and intra-nucleus. The nuclear positive neurons were distributed extensively in almost all the brain regions. This is the first report well characterizing the extensive localization of alpha SYN in the neuronal nuclei throughout the brain in normal conditions. This finding indicates an important physiological function of this molecule in the nuclei of brain neurons, which deserves further investigations. PMID- 17275198 TI - An acute post-sexual assault intervention to prevent drug abuse: updated findings. AB - Sexual assault and rape routinely produce extreme distress and negative psychological reactions in victims. Further, past research suggests that victims are at increased risk of developing substance use or abuse post-rape. The post rape forensic medical exam may itself exacerbate peritraumatic distress because it includes cues that may serve as reminders of the assault, thereby potentiating post-assault negative sequelae. To address these problems, a two-part video intervention was developed to take advantage of the existing sexual assault forensic exam infrastructure, and to specifically (a) minimize anxiety/discomfort during forensic examinations, thereby reducing risk of future emotional problems, and (b) prevent increased substance use and abuse following sexual assault. Updated findings with a sample of 268 sexual assault victims participating in the forensic medical exam and completing one or more follow-up assessments at: (1)<3 months post-assault; (2) 3 to 6 months post-assault; or (3) 6 months or longer post-assault indicated that the video was associated with significantly lower frequency of marijuana use at each time point, among women who reported use prior to the assault. PMID- 17275199 TI - Physical activity and physical activity adherence in the elderly based on smoking status. AB - This study assessed the impact of current smoking status and lifetime smoking status on physical fitness and physical activity regimen adherence as part of a larger study on walking for exercise in elderly primary care patients at a Veterans Affairs Medical Center. At baseline, 218 participants self-reported smoking status which was verified by carbon monoxide expiration. Former and current smokers responded to questions about length of time quit, average daily cigarette intake, and years a smoker. Smoking measures were re-collected at 6- and 12-month follow-ups if the participants indicated a change in smoking status. Veterans completed multiple measures of physical activity (e.g., 6-min walk, 7 day Physical Activity Recall), and adherence to a physical activity goal was assessed. The Physical Component Summary (PCS) subscale of the Medical Outcomes Study Short Form-36 (MOS SF-36) was used to assess health-related quality of life. Hierarchical regression models indicated smoking status was a predictor of the baseline 6-min walk such that smokers walked significantly shorter distances than nonsmokers. In addition, smoking status was found to be a significant predictor of adherence; however, the overall model that included smoking status as a predictor did not demonstrate a significant effect on adherence. Neither smoking status nor pack years were predictors of baseline self-reported physical activity or changes in physical activity post intervention. Results are consistent with recommendations to use physical exercise as an aid to tobacco cessation, even in aging men with extensive smoking histories. PMID- 17275200 TI - A cure for infatuation?: the potential 'therapeutic' role of pineal gland products such as melatonin and vasotocin in attenuating romantic love. PMID- 17275201 TI - Improved posttreatment functional outcome is associated with better survival in patients irradiated for metastatic spinal cord compression. AB - PURPOSE: To evaluate the potential prognostic impact of the effect of radiotherapy (RT) on motor function and of the post-RT ambulatory status on survival in metastatic spinal cord compression (MSCC) patients. METHODS AND MATERIALS: Of 1,852 patients irradiated for MSCC, 778 patients (42%) received short-course RT and 1,074 (58%) received long-course RT. The effect of RT on motor function (improvement vs. no change vs. deterioration) and the ambulatory status after RT (ambulatory vs. nonambulatory) were evaluated with respect to survival. RESULTS: The actuarial survival rate of the entire cohort was 56% at 6 months, 43% at 12 months, and 32% at 24 months. The patients in whom motor function improved after RT had a significantly better 1-year survival rate than those who had no change or deterioration of motor function (75% vs. 40% and 3%, p < 0.001). The 1-year survival rate of the patients who were ambulatory after RT was significantly better than for those who were not ambulatory (63% vs. 4%, p < 0.001). The results were confirmed in multivariate analysis. CONCLUSIONS: The response to RT and the post-RT ambulatory status are important predictors for survival in MSCC patients. This finding can be used by physicians to stratify future studies, plan further therapy, and improve follow-up strategy in these patients. PMID- 17275202 TI - Variability among breast radiation oncologists in delineation of the postsurgical lumpectomy cavity. AB - PURPOSE: Partial breast irradiation (PBI) is becoming more widely used. Accurate determination of the surgical lumpectomy cavity volume is more critical with PBI than with whole breast radiation therapy. We examined the interobserver variability in delineation of the lumpectomy cavity among four academic radiation oncologists who specialize in the treatment of breast cancer. METHODS AND MATERIALS: Thirty-four lumpectomy cavities in 33 consecutive patients were evaluated. Each physician contoured the cavity and a 1.5-cm margin was added to define the planning target volume (PTV). A cavity visualization score (CVS) was assigned (1-5). To eliminate bias, the physician of record was eliminated from the analysis in all cases. Three measures of variability of the PTV were developed: average shift of the center of mass (COM), average percent overlap between the PTV of two physicians (PVO), and standard deviation of the PTV. RESULTS: Of variables examined, pathologic resection volume was significantly correlated with CVS, with larger volumes more easily visualized. Shift of the COM decreased and PVO increased significantly as CVS increased. For CVS 4 and 5 cases, the average COM shift was 3 mm and 2 mm, respectively, and PVO was 77% and 87%, respectively. In multiple linear regression, pathologic diameter >4 cm and CVS > or =3 were significantly associated with smaller COM shift. When CVS was omitted from analysis, PVO was significantly larger with pathologic diameter > or =5 cm, days to planning <36, and older age. CONCLUSIONS: Even among radiation oncologists who specialize in breast radiotherapy, there can be substantial differences in delineation of the postsurgical radiotherapy target volume. Large treatment margins may be prudent if the cavity is not clearly defined. PMID- 17275203 TI - Tumor antivascular effects of radiotherapy combined with combretastatin a4 phosphate in human non-small-cell lung cancer. AB - PURPOSE: The tumor vascular effects of radiotherapy and subsequent administration of the vascular disrupting agent combretastatin A4 phosphate (CA4P) were studied in patients with advanced non-small-cell lung cancer using volumetric dynamic contrast-enhanced computed tomography (CT). PATIENTS AND METHODS: Following ethical committee approval and informed consent, 8 patients receiving palliative radiotherapy (27 Gy in six fractions, twice weekly) also received CA4P (50 mg/m(2)) after the second fraction of radiotherapy. Changes in dynamic CT parameters of tumor blood volume (BV) and permeability surface area product (PS) were measured for the whole tumor volume, tumor rim, and center after radiotherapy alone and after radiotherapy in combination with CA4P. RESULTS: After the second fraction of radiotherapy, 6 of the 8 patients showed increases in tumor PS (23.6%, p = 0.011). Four hours after CA4P, a reduction in tumor BV (22.9%, p < 0.001) was demonstrated in the same 6 patients. Increase in PS after radiotherapy correlated with reduction in BV after CA4P (r = 0.77, p = 0.026). At 72 h after CA4P, there was a sustained reduction in tumor BV of 29.4% (p < 0.001). Both increase in PS after radiotherapy and reduction in BV after CA4P were greater at the rim of the tumor. The BV reduction at the rim was sustained to 72 h (51.4%, p = 0.014). CONCLUSION: Radiotherapy enhances the tumor antivascular activity of CA4P in human non-small-cell lung cancer, resulting in sustained tumor vascular shutdown. PMID- 17275204 TI - Long-term results and predictive factors of three-dimensional conformal salvage radiotherapy for biochemical relapse after prostatectomy. AB - PURPOSE: Salvage radiotherapy (RT) is used to treat patients with biochemical failure after radical prostatectomy (RP). Although retrospective series have demonstrated that salvage RT will result in biochemical response in approximately 75% of patients, long-term response is much lower (20-40%). The purpose of this study was to determine prognostic factors related to the prostate-specific antigen (PSA) outcome after salvage RT. METHODS AND MATERIALS: Between 1991 and 2004, 171 patients received salvage RT at the University of Heidelberg. Patient age, margin status, Gleason score, tumor grading, pathologic tumor stage, pre-RP and pre-RT PSA levels, and time from RP to rise of PSA were analyzed. RESULTS: Median follow-up time was 39 months. The 5-year overall and clinical relapse-free survival were 93.8% and 80.8%, respectively. After RT serum PSA decreased in 141 patients (82.5%). The 5-year biochemical relapse-free survival was 35.1%. Univariate analysis showed following statistically significant predictors of PSA recurrence after RT: preoperative PSA level (p = 0.035), pathologic tumor classification (p = 0.001), Gleason score (p < 0.001), tumor grading (p = 0.004), and pre-RT PSA level (p = 0.031). On multivariate analysis, only Gleason score (p = 0.047) and pre-RT PSA level (p = 0.049) were found to be independently predictive of PSA recurrence. CONCLUSIONS: This study represents one of the largest retrospective studies analyzing the outcome of patients treated with salvage RT at a single institution. Our findings suggest that patients with Gleason score <7 and low pre-RT PSA levels are the best candidates for salvage RT, whereas patients with high-grade lesions should be considered for additional treatment (e.g., hormonal therapy). PMID- 17275205 TI - Direct aperture optimization-based intensity-modulated radiotherapy for whole breast irradiation. AB - PURPOSE: To investigate the technical and dosimetric advantages and the efficacy of direct aperture optimized intensity-modulated radiation therapy (DAO-IMRT) over standard (e.g., beamlet optimized) IMRT and conventional three-dimensional conformal radiotherapy (3D-CRT) for whole breast irradiation in supine and prone positions. METHODS AND MATERIALS: We retrospectively designed DAO-IMRT plans for 15 breast cancer patients in supine (10 patients) and prone (5 patients) positions with a goal of uniform dose coverage of the whole breast. These DAO IMRT plans were compared with standard IMRT using beamlet optimization and conventional 3D-CRT plans using wedges. All plans used opposed tangential beam arrangements. RESULTS: In all cases, the DAO-IMRT plans were equal to or better than those generated with 3D-CRT and standard beamlet-IMRT. For supine cases, DAO IMRT provided higher uniformity index (UI, defined as the ratio of the dose to 95% of breast volume to the maximum dose) than either 3D-CRT (0.88 vs. 0.82; p = 0.026) or beamlet-IMRT (0.89 vs. 0.85; p = 0.003). Direct aperture optimized IMRT also gave lower lung doses than either 3D-CRT (V20 = 7.9% vs. 8.6%; p = 0.024) or beamlet-IMRT (V20 = 8.4% vs. 9.7%; p = 0.0008) for supine patients. For prone patients, DAO-IMRT provided higher UI than either 3D-CRT (0.89 vs. 0.83; p = 0.027) or beamlet-IMRT (0.89 vs. 0.85; p = 0.003). The planning time for DAO-IMRT was approximately 75% less than that of 3D-CRT. The monitor units for DAO-IMRT were approximately 60% less than those of beamlet-IMRT. CONCLUSION: Direct aperture optimized IMRT improved the overall quality of dose distributions as well as the planning and delivery efficiency for treating whole breast in both supine and prone positions. PMID- 17275206 TI - Is adaptive treatment planning required for stereotactic radiotherapy of stage I non-small-cell lung cancer? AB - PURPOSE: Changes in position or size of target volumes have been observed during radiotherapy for lung cancer. The need for adaptive treatment planning during stereotactic radiotherapy of Stage I tumors was retrospectively analyzed using repeat four-dimensional computed tomography (4DCT) scans. METHODS AND MATERIALS: A planning study was performed for 60 tumors in 59 patients using 4DCT scans repeated after two or more treatment fractions. Planning target volumes (PTV) encompassed all tumor mobility, and dose distributions from the initial plan were projected onto PTVs derived from the repeat 4DCT. A dosimetric and volumetric analysis was performed. RESULTS: The repeat 4DCT scans were performed at a mean of 6.6 days (range, 2-12 days) after the first fraction of stereotactic radiotherapy. In 25% of cases the repeat PTV was larger, but the difference exceeded 1 mL in 5 patients only. The mean 3D displacement between the center of mass of both PTVs was 2.0 mm. The initial 80% prescription isodose ensured a mean coverage of 98% of repeat PTVs, and this isodose fully encompassed the repeat internal target volumes in all but 1 tumor. "Inadequate" coverage in the latter was caused by a new area of atelectasis adjacent to the tumor on the repeat 4DCT. CONCLUSIONS: Limited "time trends" were observed in PTVs generated by repeated uncoached 4DCT scans, and the dosimetric consequences proved to be minimal. Treatment based only on the initial PTV would not have resulted in major tumor underdosage, indicating that adaptive treatment planning is of limited value for fractionated stereotactic radiotherapy. PMID- 17275207 TI - Is mastectomy superior to breast-conserving treatment for young women? AB - PURPOSE: To examine whether modified radical mastectomy (MRM) improves outcomes compared with breast-conserving treatment (BCT) in young women. METHODS AND MATERIALS: Women aged 20-49 years, diagnosed with early breast cancer between 1989 and 1998, were identified. Management with BCT or MRM was compared for local (L), locoregional (LR), and distant relapse-free survival (DRFS) and breast cancer-specific survival (BCSS) by age group (20-39 years, 40-49 years). The analysis was repeated for patients considered "ideal" candidates for BCT: tumor size < or =2 cm, pathologically negative axillary nodes, negative margins, and no reported ductal carcinoma in situ. RESULTS: A total of 1,597 women received BCT, and 801 had MRM. After a median follow-up of 9.0 years, the outcomes (L, LR, BCSS) were worse for the younger age group; however, the outcomes were not statistically different by type of local treatment. For women aged 20-39 years considered "ideal" for BCT, those treated with BCT had slightly lower LRFS compared with those treated with MRM (p = 0.3), but DRFS and BCSS were similar. CONCLUSIONS: A difference in LRFS at 10 years potentially favored MRM among women aged 20-39 years considered "ideal" BCT candidates but was not statistically significant and did not translate into a noticeable difference in DRFS or BCSS. Our data suggest that young age alone is not a contraindication to BCT. PMID- 17275208 TI - Patterns of failure and local control after intraoperative electron boost radiotherapy to the presacral space in combination with total mesorectal excision in patients with locally advanced rectal cancer. AB - PURPOSE: To evaluate local control and patterns of failure in patients treated with intraoperative electron beam radiotherapy (IOERT) after total mesorectal excision (TME), to appraise the effectiveness of intraoperative target definition. METHODS AND MATERIALS: We analyzed the outcome of 243 patients with rectal cancer treated with IOERT (median dose, 10 Gy) after TME. Eighty-eight patients received neoadjuvant and 122 patients adjuvant external beam radiotherapy (EBRT) (median dose, 41.4 Gy), and in 88% simultaneous chemotherapy was applied. Median follow-up was 59 months. RESULTS: Local failure was observed in 17 patients (7%), resulting in a 5-year local control rate of 92%. Only complete resection and absence of nodal involvement correlated positively with local control. Considering IOERT fields, seven infield recurrences were seen in the presacral space, resulting in a 5-year local control rate of 97%. The remaining local relapses were located as follows: retrovesical/retroprostatic (5), anastomotic site (2), promontorium (1), ileocecal (1), and perineal (1). CONCLUSION: Intraoperative electron beam radiotherapy as part of a multimodal treatment approach including TME is a highly effective regimen to prevent local failure. The presacral space remains the site of highest risk for local failure, but IOERT can decrease the percentage of relapses in this area. PMID- 17275209 TI - Anti-diarrheal activity of methanol extract of Litsea polyantha bark in mice. AB - The anti-diarrheal activity of methanol extract of dried bark and aerial parts of Litsea polyantha (MELP) has been evaluated in mice using different models (castor oil-induced diarrhea and propulsive gut motility in mice). MELP (50, 75, 100 mg/kg, p.o.) significantly (P<0.01) reduced the onset of diarrhea, fecal excretion and also showed a significant (P<0.001) reduction in gastrointestinal motility on charcoal meal test in mice. The results of the study support the folklore use of the plant for diarrheal remedies. PMID- 17275210 TI - [Endometriosis anatomoclinical entities]. AB - The aim of this literature review is to precise definition, anatomoclinical entities and natural history of endometriosis to allow clinical guideline establishment. DEFINITION: Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterus. This histologic definition does not implicate symptoms. Macroscopic lesions supposed to be endometriosis are not always confirmed by histology. Histology is recommended to confirm endometriosis. Negative histology does not exclude endometriosis. ANATOMOCLINICAL ENTITIES: Three endometriosis entities are described: peritoneal endometriosis, ovarian endometrial cyst, and deeply infiltrating endometriosis. There is no evidence to establish a different pathogenesis of theses entities. ENDOMETRIOSIS NATURAL HISTORY: It is not well known. It may progress or regress with or without treatment. There is no evidence of treatment in case of asymptomatic endometriosis. There is an association between endometriosis and ovarian cancer. The risk of endometriosis malignant transformation is still a subject of controversy. There is no evidence for a specific oncologic follow-up of woman having endometriosis. PMID- 17275211 TI - Reinforcement omission in concurrent fixed-interval and random-interval schedules. AB - The present experiment examined overall and local effects of omission of reinforcers in a choice situation. Pigeons' key-pecking responses were reinforced under concurrent fixed-interval and random-interval schedules of food presentation. After some weeks of baseline sessions in which the probability of reinforcement was 1.00, approximately 25% of food presentations from the fixed interval schedule were omitted and replaced by timeout periods. In such omission sessions, the overall relative rates of responding to the fixed-interval schedule became lower than those in the baseline sessions. On the other hand, when relative rates of responding to the fixed-interval schedule in the omission sessions were calculated separately for fixed-interval cycles preceded by timeout periods and those preceded by food presentations, the relative rates in the former type of fixed-interval cycles were higher than those in the latter type for three out of four pigeons. These results mean that relative rates of responding cannot always be regarded as reflecting a relative value of an alternative, and that the overall effect of the omission of fixed-interval reinforcers is not reducible to the local effect of omission. PMID- 17275212 TI - Comorbidity of substance use disorders and other psychiatric disorders among adolescents: evidence from an epidemiologic survey. AB - This paper extends our knowledge of comorbidity of substance use disorders (SUDs) and other psychiatric disorders by examining comorbidity of specific types of SUDs and risk of comorbidity separately for abuse and dependence. The research question is whether there is specificity of risk for comorbidity for different SUDs and whether greater comorbidity is associated with dependence. Data are presented from a probability sample of 4175 youths aged 11-17 assessed with the NIMH DISC-IV and self-administered questionnaires. SUDs outcomes are alcohol, marijuana and other substances in past year. Mean number of other comorbid disorders ranged from 1.9 for marijuana abuse to 2.2 for other substance abuse and 1.9 for marijuana dependence to 2.8 for other substance dependence. None of the abuse SUDs does not increase risk of anxiety disorders, but dependence does. Both abuse and dependence increased risk of comorbid mood disorders. Similar results were observed for disruptive disorders. Patterns of comorbidity varied by substance, by abuse versus dependence, and by category of other psychiatric disorders. In general, there was greater association of comorbidity with other disorders for dependence versus abuse. Marijuana is somewhat less associated with other disorders than alcohol or other substances. The strongest association is for comorbid disruptive disorders, regardless of SUDs category. Having SUDs and comorbid other psychiatric disorders was associated with substantial functional impairment. Females with SUDs tended to have higher rates of comorbid disorders, as did older youths. There were no differences observed among ethnic groups. When comorbidity of SUDs with other disorders was examined, controlling for other non SUDs disorders for each specific disorder examined, the greater odds for dependence versus abuse essentially disappeared for all disorders except disruptive disorders, suggesting larger number of comorbid non-SUDs in part account for the observed effects for dependence. PMID- 17275213 TI - Early experience with racial discrimination and conduct disorder as predictors of subsequent drug use: a critical period hypothesis. AB - A critical period hypothesis linking early experiences with both racial discrimination and conduct disorder (CD) with subsequent drug use was examined in a panel of 889 African American adolescents (age 10.5 at time 1) and their parents. Analyses indicated that these early experiences did predict use by the adolescents at time 3 (T3)-5 years later. These relations were both direct and indirect, being mediated by an increase in affiliation with friends who were using drugs. The relations existed controlling for parents' reports of their use, discrimination experiences, and their socioeconomic status (SES). The impact of these early experiences on African American families is discussed. PMID- 17275214 TI - Pubertal maturation and the development of alcohol use and abuse. AB - OBJECTIVE: To examine the impact of various aspects of puberty on risk of using alcohol and developing alcohol use disorder (AUD). METHODS: Data come from the Great Smoky Mountains Study, a longitudinal study of a representative sample of 1420 youth aged 9-13 at recruitment. Participants were interviewed annually to age 16. A parent was also interviewed. Information was obtained about use of a range of drugs including alcohol, drug abuse and dependence, other psychiatric disorders, life events, and a wide range of family characteristics. Pubertal hormones were assayed annually from blood samples, and morphological development was assessed using a pictorial measure of Tanner stage. RESULTS: Controlling for age, Tanner stage predicted alcohol use and AUD in both boys (OR 1.58, 95% CI 1.18-2.22) and girls (OR 1.62, 95% CI 1.17-2.23). The effect of morphological development was strongest in those who matured early. Early pubertal maturation predicted alcohol use in both sexes, and AUD in girls. The highest level of excess risk for alcohol use was seen in early maturing youth with conduct disorder and deviant peers. Lax supervision predicted alcohol use in early maturing girls, while poverty and family problems were predictive in early maturing boys. CONCLUSIONS: Among the many biological, morphological, and social markers of increasing maturation, the visible signs of maturity are important triggers of alcohol use and AUD, especially when they occur early and in young people with conduct problems, deviant peers, problem families and inadequate parental supervision. PMID- 17275215 TI - Interpreting treatment effects when cases are institutionalized after treatment. AB - Drug treatment clients are at high risk for institutionalization, i.e., spending a day or more in a controlled environment where their freedom to use drugs, commit crimes, or engage in risky behavior may be circumscribed. For example, in recent large studies of drug treatment outcomes, more than 40% of participants were institutionalized for a portion of the follow-up period. When longitudinal studies ignore institutionalization at follow-up, outcome measures and treatment effect estimates conflate treatment effects on institutionalization with effects on many of the outcomes of interest. In this paper, we develop a causal modeling framework for evaluating the four standard approaches for addressing this institutionalization confound, and illustrate the effects of each approach using a case study comparing drug use outcomes of youths who enter either residential or outpatient treatment modalities. Common methods provide biased estimates of the treatment effect except under improbable assumptions. In the case study, the effect of residential care ranged from beneficial and significant to detrimental and significant depending on the approach used to account for institutionalization. We discuss the implications of our analysis for longitudinal studies of all populations at high risk for institutionalization. PMID- 17275216 TI - Determination of whole prokaryotic phylogeny by the development of a random extraction method. AB - The construction of accurate prokaryotic phylogeny is important not only in the field of evolutionary biology, but also in microbiology and pathology. However, in constructing a phylogenetic tree to trace prokaryotic evolution, the phylogenetic relationship is often changed by the choice of species. For the estimation of the accurate lineage of prokaryotes, a new method, named the "random extraction method", was developed. In this method, 16S rRNA sequence data were randomly extracted 1000 times from each closely-related taxa such as seven phyla of Eubacteria and one domain of Archaea and phylogenetic trees were constructed by the data to clarify the relationship of those groups. Next, the tree topology was counted and the most supported tree topology was found as the most plausible phylogenetic tree. To evaluate the reliability of each node, we developed the "Branching rate" (BR) and calculated for every tree. And also, computational simulation analysis was carried out to confirm these methods. On the assumption that the root of life is between Archaea and Eubacteria, the obtained phylogenetic relationships of phyla are the following. At first, Archaea (Euryarchaeota, Crenarchaeota and Korarchaeota) diverged, and Thermotogales, Cyanobacteria and Chlamydiales diverged in this order, then Firmicutes (Actinobacteria and Bacillus/Clostridium group cluster) and Proteobacteria (alpha and beta/gamma cluster) diverged. In addition, it was shown by the BR that the position of the node of Firmicutes Actinobacteria and Firmicutes Bacillus/Clostridium was changeable for each extraction. Therefore, it was suggested that the differences among the phylogenetic trees of prokaryotes were caused by the influence of these phyla. PMID- 17275217 TI - Bacteriophage-based vectors for site-specific insertion of DNA in the chromosome of Corynebacteria. AB - In Corynebacterium diphtheriae, diphtheria toxin is encoded by the tox gene of some temperate corynephages such as beta. beta-like corynephages are capable of inserting into the C. diphtheriae chromosome at two specific sites, attB1 and attB2. Transcription of the phage-encoded tox gene, and many chromosomally encoded genes, is regulated by the DtxR protein in response to Fe(2+) levels. Characterizing DtxR-dependent gene regulation is pivotal in understanding diphtheria pathogenesis and mechanisms of iron-dependent gene expression; although this has been hampered by a lack of molecular genetic tools in C. diphtheriae and related Coryneform species. To expand the systems for genetic manipulation of C. diphtheriae, we constructed plasmid vectors capable of integrating into the chromosome. These plasmids contain the beta-encoded attP site and the DIP0182 integrase gene of C. diphtheriae NCTC13129. When these vectors were delivered to the cytoplasm of non-lysogenic C. diphtheriae, they integrated into either the attB1 or attB2 sites with comparable frequency. Lysogens were also transformed with these vectors, by virtue of the second attB site. An integrated vector carrying an intact dtxR gene complemented the mutant phenotypes of a C. diphtheriae DeltadtxR strain. Additionally, strains of beta susceptible C. ulcerans, and C. glutamicum, a species non-permissive for beta, were each transformed with these vectors. This work significantly extends the tools available for targeted transformation of both pathogenic and non-pathogenic Corynebacterium species. PMID- 17275218 TI - A novel signature-tagged mutagenesis system for Streptococcus suis serotype 2. AB - Streptococcus suis is an economically important, zoonotic pathogen causing death and disease in swine. The objectives of this study were to develop a signature tagged mutagenesis (STM) system for S. suis serotype 2 and to identify genes required for in vivo virulence. Identification of such candidate genes may lead to a better understanding of the pathogenesis of S. suis and may provide substrate for the discovery of new vaccines. A novel STM approach was designed to allow for a higher throughput assay of mutants using the Luminex xMAP system. Additionally, to speed the identification process, a direct genomic DNA sequencing method was developed that overcomes the problems associated with the presence of repetitive insertion sequences. Approximately 2600 mutants were screened through both mouse and caesarian-derived, colostrum-deprived (CDCD) pig models. The disrupted ORF was identified for each potential attenuated mutant, and mutants with distinct and unique mutated ORFs were analyzed individually for attenuation in mouse and CDCD pig models. A variety of genes were identified, including previously known genes essential to the virulence of other organisms, genes involved in capsule biosynthesis, a regulator of suilysin expression, and several conserved or predicted genes. Of the 22 mutants identified as attenuated in either animal model, eight insertion mutants caused no mortality in both mouse and pig models. PMID- 17275219 TI - Genotyping canine distemper virus (CDV) by a hemi-nested multiplex PCR provides a rapid approach for investigation of CDV outbreaks. AB - CDV is a highly contagious viral pathogen causing a lethal systemic disease in dogs and other carnivores. Several lineages or genotypes of CDV exist that are variously distributed throughout several continents. Legal or uncontrolled trading of animals may modify the epidemiology of CDV, introducing novel strains in CDV-naive areas or accounting for the resurgence of CDV in areas where vaccine prophylaxis was effective and successful to control the disease. A hemi-nested PCR system was developed to genotype strains of the major CDV lineages, America 1, Europe, Asia-1, Asia-2 and Arctic. The assay was tested using a collection of 27 laboratory and vaccine strains and of 36 field CDV strains. Distinct lineages could be differentiated by specific primers targeted to the H gene. The method could be useful for molecular epidemiological studies of CDV, providing a tool for large-scale studies, and for the diagnosis of vaccine-related disease. PMID- 17275221 TI - Decreases in urinary pheromonal activities in male mice after exposure to 3 methylchoranthrene. AB - Many classes of environmental pollutants, which are found at significant levels in the environment, affect the reproductive functions. The gonadal functions of various animals are regulated by pheromones excreted from mating partners. Pheromones in male urine play essential roles in the sexual maturation of female mice. Pheromones are received by sensory neurons in the vomeronasal organ, which innervate to the accessory olfactory bulb (AOB). The effects of a typical aromatic environmental pollutant (3-methylchoranthrene) on excretion of pheromones from male mice were explored based on neuronal Fos responses of the AOB of female mice. On days 1 and 3 after intraperitoneal administration of 3 methylchoranthrene (3-MC), the density of Fos-immunoreactive (Fos-ir) cells in the AOB of female mice after exposure to urine excreted from the administered males was lower than that after exposure to urine from non-administered males. These results suggest that 3-MC blocks chemical communication from male to female mice by reducing pheromonal activities. PMID- 17275220 TI - Impact of carbon nanotube exposure, dosage and aggregation on smooth muscle cells. AB - Carbon nanotubes (CNT), despite their diverse application potential, have demonstrated adverse impacts in vitro and in vivo. Previous studies have focused on the combined in vitro cytotoxic impact of CNT aggregates and associated nanoparticulate impurities. However, the isolated effect of CNT aggregates and associated non-aggregated nanoparticulates have not been addressed in detail. In this work, the impact of single-walled nanotubes (SWNT) on rat aortic smooth muscle cells (SMC) was examined for SWNT (0.0-0.1 mg/ml) over a 3.5-day time course. Cell culture medium was filtered to remove the aggregate material and both nanomaterial (un-filtered) and filtered SWNT media were used to examine cell growth. In general, the removal of SWNT aggregates from cell culture test medium by filtration increased the SMC number in comparison to unfiltered medium at pre filtered SWNT dosages below 0.1 mg/ml. However, at 0.1 mg/ml, both filtered and unfiltered media exhibited a similar decrease in cell number relative to the control medium. The filtered medium was characterized and contained both suspended nanoparticles as well as a small quantity of SWNT, which may have contributed to the observed cell growth inhibition. As a comparison to the SWNT, activated carbon (0.1 mg/ml), a nanoporous, microparticulate carbon material, was found to be less inhibitory to SMC growth than the SWNT at the same dosage, implying an inverse proportionality between carbon nanomaterial size regimes and cell growth inhibition. PMID- 17275222 TI - Benzo(a)pyrene inhibits growth and functional differentiation of mouse bone marrow-derived dendritic cells. Downregulation of RelB and eIF3 p170 by benzo(a)pyrene. AB - In this study, we have investigated effects of benzo(a)pyrene (BP) on growth and functional differentiation of mouse bone marrow (BM)-derived dendritic cells (DC). 1 microM BP dramatically inhibited growth of BM cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL 4). Although little alterations in surface expression of CD11c, major histocompatibility complex (MHC II), and CD86 molecules characteristic of mature DC were induced by BP, production of cytokines including IL-12, IL-10, and TNF alpha, and allogeneic T cell stimulating ability were severely impaired. Some of the effects of BP were dependent on arylhydrocarbon receptor (AhR), because alpha naphthoflavone, an AhR antagonist, suppressed the effects of BP on IL-12 production and T cell stimulating ability, but not on DC proliferation. Expression of RelB, a transcription factor necessary for DC differentiation and function, and eIF3 p170, a subunit of eukaryotic translation initiation factor (eIF)3, was reduced upon BP treatment. PMID- 17275223 TI - Progesterone induces the expression of vascular endothelial growth factor (VEGF) 120 and Flk-1, its receptor, in bovine granulosa cells. AB - Vascular endothelial growth factor (VEGF) isoforms (VEGF 120 and VEGF 164) secreted by granulosa cells are involved in thecal angiogenesis during follicular development in the bovine ovary. The follicular fluid in the developing follicle includes a slight amount of the progesterone. However, the progesterone (P4) effects on VEGF120 and VEGF164 isoforms have not been well characterized in the bovine granulosa cells. We investigated the effects of progesterone on the gene expression of hypoxia-inducible factor 1alpha (HIF-1alpha, transcription factor), VEGF120, VEGF164 and Flk-1, its receptors, in cultured bovine granulosa cells. Messenger RNA expression for HIF-1alpha, VEGF120, VEGF164 and Flk-1 was quantified using real-time PCR methods. The levels of VEGF120, HIF-1alpha and Flk 1 mRNAs were increased significantly by P4 at a concentration of 10 ng/ml. In contrast, the expression of VEGF 164 gene is inhibited by P4. The level of VEGF120 and Flk-1 mRNAs in the granulosa cells treated with 10 ng/ml progesterone plus 1 ng/ml estradiol significantly decreased compared with progesterone alone. In contrast, the addition of 1 ng/ml estradiol to the culture medium increased the expression of VEGF164 gene. In conclusion, our data demonstrated that progesterone might stimulate the expression of the VEGF120 via HIF-1alpha, transcription factor, in bovine granulosa cells. These results suggest the hormone-dependent expression pattern of VEGF isoforms during follicular development. Thus, our study suggested the expression of VEGF isoforms in granulosa cells might be controlled by a different pathway during follicle development in cow. PMID- 17275224 TI - Field fertility of frozen-thawed boar sperm at low doses using non-surgical, deep uterine insemination. AB - The lowest dose of frozen-thawed boar sperm used for deep uterine artificial insemination (DUI) of sows has been 100x10(6). A three stage field study was performed to establish to what level the dose of frozen-thawed sperm used for DUI could be reduced without adversely affecting the fertility of the sow. In stage 1, 15 sows were inseminated twice with 1000x10(6) fresh or frozen-thawed sperm at 24 and 36 h post-detection of oestrus. In stage 2, 262 sows were inseminated with 62.5, 250 or 1000x10(6) fresh or frozen-thawed sperm at 24, 36, or 24 and 36 h after detection of oestrus. Stage 3 involved post mortem investigation of the uterine lining to assess damage caused by insertion of the insemination catheter. All sows inseminated in stage 1 of the study farrowed. In stage 2, the non-return (NRR) and farrowing rates of each group were compared to a control double cervical insemination of 3250x10(6) fresh sperm. As few as 62.5x10(6) fresh sperm could be deposited at a single insemination without reduction in NRR or farrowing rates compared with the control group. A double DUI with 250x10(6) frozen-thawed sperm was required before fertility was equivalent to the controls. Investigation of the uterine lining after insertion of the DUI catheter revealed evidence of bleeding, warranting further investigation of the viability of widespread use of the Firflex catheter, despite the promising fertility achieved here with low doses of spermatozoa. PMID- 17275225 TI - Efficacy on menopausal neurovegetative symptoms and some plasma lipids blood levels of an herbal product containing isoflavones and other plant extracts. AB - OBJECTIVES: To assess the efficacy of a product containing isoflavones and other plant extracts (BIO) on whole menopausal symptomatology and plasma lipids profile. METHODS: Multicentre, randomized, double blind, placebo controlled clinical investigation on 125 menopausal women randomly assigned to two groups treated for 6 months with placebo or one tablet daily of an herbal product containing 72 mg/dose of isoflavones of different plants origin and other plant extracts (BIO). Primary end-point: Kupperman Menopause Index (KI) variations; secondary end-point: activity on plasma lipids profile and clinical global impression (CGI) on efficacy and tolerability by investigators and patients. The usual parametric test (paired Student t test) was performed to evaluate the significance. In case of non-applicability of parametric tests, the non parametric Mann-Whitney U test was used. The differences where considered significant at p<0.05 level. RESULTS: At the end of treatment in both groups KI showed a significant decrease (p<0.001). However, in the BIO group the KI reduction was significantly higher (p=0.0265) than in the placebo group after 4 and 6 months of treatment. In the BIO treated patients the LDL cholesterol showed a borderline but not significant reduction compared to placebo (p=0.0608) and triglyceride (TG) a significant (p=0.0151) decrease compared to placebo. The investigator's and patient's CGI on BIO group where superior as compared to placebo. Clinical tolerability was good in booth groups. CONCLUSION: On the basis of positive effects on KI and lipids profile as well as of good clinical tolerability, BIO can be considered one of the possible alternative therapy for conventional HRT. PMID- 17275226 TI - The effects of black cohosh therapies on lipids, fibrinogen, glucose and insulin. AB - OBJECTIVE: Black cohosh (Actaea racemosa) is an herb commonly used to treat menopausal symptoms. Little is known about its effect on other physiologic parameters that could result in untoward events. This study examines the effect of black cohosh on lipids, fibrinogen, glucose and insulin. METHODS: Three hundred and fifty-one, 45-55 years old, peri or post-menopausal women experiencing vasomotor symptoms participated in a 3-month, double blind trial with randomization to: (1) black cohosh (160 mg daily); (2) multibotanical including black cohosh (200 mg daily); (3) multibotanical plus soy diet counseling; (4) conjugated equine estrogen .625 mg, with or without medroxyprogesterone acetate 2.5mg daily, for women with or without a uterus, respectively; (5) placebo. Baseline and month 3 total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), triglyceride, insulin, glucose, and fibrinogen serum concentrations were measured in 310 women. Baseline information was also collected on medical history, demographic characteristics, and diet. RESULTS: There were no statistically significant differences in the adjusted mean change from baseline to 3 months between the herbal groups and placebo in total cholesterol, LDL, HDL, triglycerides, glucose, and insulin. Adjusted fibrinogen levels appear to increase in the multibotanical treatment group in comparison with the other herbal groups and placebo overall (P = .02), but there was no statistically significant difference in the pairwise test against placebo (P = .11). CONCLUSIONS: Black cohosh containing therapies had no demonstrable effects on lipids, glucose, insulin or fibrinogen. PMID- 17275227 TI - The enhancing effect of synthetical borneol on the absorption of tetramethylpyrazine phosphate in mouse. AB - The main purpose of this study was to illustrate the effect of synthetical borneol (SB) on the plasma and brain concentration profile of tetramethylpyrazine phosphate (TMPP) in mice after oral administration of TMPP without or with different amounts of SB. The concentrations of TMPP on the plasma and brain in mice were determined by GC-FID. The pharmacokinetic parameters were computed by software program 3p97. Our data showed that after oral administration of 15, 30, 90 mg kg(-1) of SB, oral bioavailability of TMPP in plasma was 1.52, 2.21, 2.95 times increase, respectively, than that without SB, and 1.12, 1.62, 1.93 times increase, respectively, in brain tissue. The pharmacokinetic data were simulated by non-linear least squares. The results showed that both open two-compartment model and one-order absorption were fitted to TMPP plasma and brain concentration time course in vivo in mice. The MRT of TMPP showed same results under the conditions without or with SB. SB did enhance the oral absorption of TMPP and the concentration of TMPP in brain tissue, especially in the early period. But the use of SB did not change the behavior in vivo of TMPP. PMID- 17275228 TI - Effects of bacterial lipopolysaccharide on the pharmacokinetics of metformin in rats. AB - It was reported that the hepatic microsomal cytochrome P450 (CYP) 2C11, 2D1, and 3A1 (not via the CYP1A2, 2B1/2, and 2E1) were involved in the metabolism of metformin in rats. It was also reported that the expressions of CYP2C11 and 3A2 decreased in rats pretreated with Klebsiella pneumoniae lipopolysaccharide (KPLPS). Therefore, the pharmacokinetic parameters of metformin could be changed in rats pretreated with KPLPS. Hence, the pharmacokinetic parameters of metformin were compared after both intravenous and oral administration of the drug at a dose of 100mg/kg to control rats and rats pretreated with KPLPS. After intravenous administration of metformin to rats pretreated with KPLPS, the total area under the plasma concentration-time curve from time 0 to infinity (AUC) of the drug was significantly greater (40.5% increase) than the controls due to significantly smaller CL value (27.7% decrease) than the controls. The significantly smaller CL value could be due to significantly smaller both the CL(R) and CL(NR) values (34.0% and 18.1% decrease, respectively) than the controls. The significantly smaller CL(NR) value could be due to decrease in the expressions of CYP2C11 and 3A2 in rats pretreated with KPLPS. After oral administration of metformin, the AUC of the drug was not significantly different between two groups of rats, and this may be at least partly due to decrease in absorption from the gastrointestinal tract compared with the controls. PMID- 17275229 TI - Study on the thermal stability of green fluorescent protein (GFP) in glucose parenteral formulations. AB - Large volume parenteral solutions (LVPS) that are widely used in the healthcare system must be processed by moist-heat treatment to an assured sterility level in which the efficacy is measured by a bioindicator (BI) that provides fast, accurate and reliable results. This study evaluated the thermal stability of green fluorescent protein (GFP) into glucose-based LVPS (1.5-50%) solutions to determine its utility as a BI for thermal processes. GFP, expressed by Escherichia coli, isolated/purified by TPP/HIC, was diluted in buffered (each 10mM: Tris-EDTA, pH 8; phosphate, pH 6 and 7; acetate, pH 5) and in water for injection (WFI; pH 6.70+/-0.40) glucose solutions (1.5-50%) and exposed to constant temperatures from 80 degrees C to 95 degrees C. The thermal stability was expressed in decimal reduction time (D-value, time required to reduce 90% of the GFP fluorescence intensity). At 95 degrees C, the D-values for GFP in 1.5-50% glucose were: (i) 1.63+/-0.23 min (pH 5); (ii) 2.64+/-0.26 min (WFI); (iii) 2.50+/-0.18 min (pH 6); (iv) 3.24+/-0.28 min (pH 7); (v) 2.89+/-0.44 min (pH 8). By the convenient measure of fluorescence intensity and its thermal stability, GFP has the potential as a BI to assay the efficacy of moist-heat processing of LVPS at temperatures < or =100 degrees C. PMID- 17275230 TI - Vascular targeting of doxorubicin using cationic liposomes. AB - Tumor vessel has been recognized as an important target for anticancer therapy. Cationic liposomes have been shown to selectively target tumor endothelial cells, thus can potentially be used as a carrier for chemotherapy agents. In this study, cationic liposomes containing 20 mol% cationic lipid dimethyl dioctadecyl ammonium bromide (DDAB) and loaded with doxorubicin (DOX) were prepared and characterized. The cationic liposomal DOX showed 10.8 and 9.1 times greater cytotoxicity than control PEGylated liposomal DOX in KB oral carcinoma and L1210 murine lymphocytic leukemia cells, and 7.7- and 6.8-fold greater cytotoxicity compared to control neutral non-PEGylated liposomal DOX, repectively, in these two cell lines. Although cationic liposomal DOX had higher tumor accumulation at 30 min after intravenous administration compared to control liposomes (p<0.05), DOX uptake of these liposomes at 24h post-injection was similar to that of PEGylated liposomal DOX (p>0.05) and approximately twice the levels of the free drug and non-PEGylated liposomes. In a murine tumor model generated using L1210 cells, increased survival rate was obtained with cationic liposomal DOX treatment compared to free DOX (p<0.01), neutral liposome control (p<0.01), as well as PEGylated liposomes (p<0.05). In conclusion, the cationic liposomal DOX formulation produced superior in vitro cytotoxicity and in vivo antitumor activity, and warrants further investigation. PMID- 17275232 TI - Some investigations into non-passive listening. AB - Our knowledge of the function of the auditory nervous system is based upon a wealth of data obtained, for the most part, in anaesthetised animals. More recently, it has been generally acknowledged that factors such as attention profoundly modulate the activity of sensory systems and this can take place at many levels of processing. Imaging studies, in particular, have revealed the greater activation of auditory areas and areas outside of sensory processing areas when attending to a stimulus. We present here a brief review of the consequences of such non-passive listening and go on to describe some of the experiments we are conducting to investigate them. In imaging studies, using fMRI, we can demonstrate the activation of attention networks that are non specific to the sensory modality as well as greater and different activation of the areas of the supra-temporal plane that includes primary and secondary auditory areas. The profuse descending connections of the auditory system seem likely to be part of the mechanisms subserving attention to sound. These are generally thought to be largely inactivated by anaesthesia. However, we have been able to demonstrate that even in an anaesthetised preparation, removing the descending control from the cortex leads to quite profound changes in the temporal patterns of activation by sounds in thalamus and inferior colliculus. Some of these effects seem to be specific to the ear of stimulation and affect interaural processing. To bridge these observations we are developing an awake behaving preparation involving freely moving animals in which it will be possible to investigate the effects of consciousness (by contrasting awake and anaesthetized), passive and active listening. PMID- 17275233 TI - Single-metal deposition (SMD) as a latent fingermark enhancement technique: an alternative to multimetal deposition (MMD). AB - This paper proposes an alternative solution to multimetal deposition (MMD) for the development of latent fingermarks on non-porous and porous surfaces. MMD offers a good sensitivity, however it is very time-consuming and requires many reagents to be carried out. Single-metal deposition (SMD) replaces the silver enhancement of the gold colloids by a gold enhancement procedure. This reduces the number of baths by one as well as the number of reagents and their cost, utilizes reagents with a longer shelf life, and most importantly reduces the labor-intensity of the procedure. It offers quasi-identical results to MMD and thus makes a very attractive alternative. PMID- 17275234 TI - Identification of victims from two mass-graves in Serbia: a critical evaluation of classical markers of identity. AB - Reliable identification of victims in mass graves is of humanitarian and human rights concern. Because mass graves in the former Yugoslavia usually contain an 'open' population of large numbers of unknown victims and therefore 'presumptive identifications' based on classical markers of identity are problematic, greater reliance is now made on blind matches between victim DNA and a database of donated blood DNA samples from family members of missing persons. Nevertheless, there will always remain a legal and social need to show good correspondence between a DNA-derived identification and classical markers of identity. Moreover, pathologists and anthropologists, who must continue to rely in much of their case work on classical methods, need to evaluate on an ongoing basis the goodness of fit between the two paradigms of identification. The Institute of Forensic Medicine and Laboratory for Anthropology in Belgrade participated in 2001 in the exhumation and identification of more than 300 bodies of Kosovar Albanians interred in two mass graves at Batajnica, near Belgrade, Serbia. Of these bodies, 136 were legally identified by the end of 2003 providing an opportunity for the forensic experts to evaluate their post-mortem findings of classical markers of identity. Sex and age at death of young to middle-aged adults were reliably determined but old adults were markedly under-aged. Stature was reconstructed reliably in 77% of cases. Dental status contributed little to identification efforts. In no case did classical markers of identity require rejection of the DNA-based identification. It is concluded that: sex determination from pelvic bones is very reliable, as are age at death estimates from pelvic and rib standards for young to middle-aged adults but that uncertainty intervals for age at death in older adults be broadened or refined by creation of local osteological standards. PMID- 17275231 TI - The role of bone morphogenetic protein 4 in inner ear development and function. AB - Bone Morphogenetic Protein 4 (BMP4) is a member of the TGF-beta superfamily and is known to be important for the normal development of many tissues and organs, including the inner ear. Bmp4 homozygous null mice die as embryos, but Bmp4 heterozygous null (Bmp4(+/-)) mice are viable and some adults exhibit a circling phenotype, suggestive of an inner ear defect. To understand the role of BMP4 in inner ear development and function, we have begun to study C57BL/6 Bmp4(+/-) mice. Quantitative testing of the vestibulo-collic reflex, which helps maintain head stability, demonstrated that Bmp4(+/-) mice that exhibit circling behavior have a poor response in the yaw axis, consistent with semicircular canal dysfunction. Although the hair cells of the ampullae were grossly normal, the stereocilia were greatly reduced in number. Auditory brainstem responses showed that Bmp4(+/-) mice have elevated hearing thresholds and immunohistochemical staining demonstrated decreased numbers of neuronal processes in the organ of Corti. Thus Bmp4(+/-) mice have structural and functional deficits in the inner ear. PMID- 17275235 TI - A new trial liposteroid (dexamethasone palmitate) therapy for intractable epileptic seizures in infancy. AB - West syndrome (WS) is a severe age-dependent intractable epilepsy in infants that frequently results in mental retardation. ACTH or glucocorticoids are among several effective treatments in WS, but the relative advantages and disadvantages of these two therapies are still unknown. In a previous study, liposteroid (LS; dexamethasone palmitate) was used for the treatment of WS and compared with ACTH therapy in relation to therapeutic effect and adverse reactions. In this study, a new regimen of LS therapy was tried for WS and its related syndrome in an attempt to hasten the onset of the therapeutic effect and reduce the relapse rate. A single intravenous injection of LS (0.25mg/kg) was administered 12 times in 1 month (total dosage 3.0mg/kg) to four patients with WS and with post-WS aged 5-25 months, and one patient with Lennox-Gastaut syndrome (post-WS) aged 84 months. All five patients had daily seizures uncontrolled by conventional antiepileptic drugs, such as VPA, CZP or ZNS. Nodding spasm and hypsarrhythmia on EEG disappeared in one patient with WS within four doses. More than 50% decrease in seizures, and EEG improvement, were found in other two patients. No notable effects were seen in the other two patients. There were no clinically significant adverse reactions throughout the therapy. Efficacy can be determined in this new experimental LS therapy earlier than with conventional LS therapy. In this small study, a new protocol for LS therapy could be completed safely. This regimen may be useful for those susceptible to adverse reactions from conventional treatment or those unresponsive to other treatments. PMID- 17275236 TI - The synergism of age and db/db genotype impairs wound healing. AB - Both diabetes and advanced age have been implicated in delaying wound repair. However, the contribution of age alone has not been shown clinically to significantly impair the ability to heal. To determine the contribution of age and db/db genotype multiple wound healing parameters were determined in young db/db mice, aged db/db mice, age-matched non-db/db control and wild-type C57BL/6 mice. Biomechanical properties (breaking load and tensile stiffness), epithelialization, and collagen deposition were determined for the four groups of mice 14 days after wounding with suture-closed incisional wounds. While neither hyperglycemia nor age alone caused impairment in biomechanical properties, the combination of age and db/db genotype resulted in a 36% reduction in stiffness and a 42% reduction in breaking load, when compared to young control mice, suggesting poor quality of healing. Statistically significant differences in the volume of granulation tissue deposited within the wound site were also observed, with the aged db/db mice displaying more than any other group, suggesting greater dermal loss from the dermal edges of incisional wounds in aged db/db mice, suggesting that the combination of age and diabetes act synergistically to impair healing in mice with type 2 diabetes. Interestingly, the impairment occurs independently of the prevailing glycemia, supporting the hypothesis that diabetes in synergy with advanced age has downstream effects, leading to further impairment, necessitating initiation of early and aggressive intervention in elderly patients with diabetic foot ulcers. PMID- 17275237 TI - Hematopoietic stem cell aging: mechanism and consequence. AB - Advancing age is frequented by the onset of a variety of hematological conditions characterized by diminished homeostatic control of blood cell production. The fact that upstream hematopoietic stem and progenitor cells are obligate mediators of homeostatic control of all blood lineages, has implicated the involvement of these cells in the pathophysiology of these conditions. Indeed, evidence from our group and others has suggested that two of the most clinically significant age associated hematological conditions, namely, the diminution of the adaptive immune system and the elevated incidence of myeloproliferative diseases, have their origin in cell autonomous changes in the functional capacity of hematopoietic stem cells. PMID- 17275238 TI - Unusual imaging characteristics of complicated hydatid disease. AB - Hydatid disease, a worldwide zoonosis, is caused by the larval stage of the Echinococcus tapeworm. Although the liver and the lungs are the most frequently involved organs in the body, hydatid cysts of other organs are unusual. Radiologically, they usually demonstrate typical imaging findings, but unusual imaging characteristics of complicated cyst of hydatid disease, associated with high morbidity and mortality, are rarely described in the literature. The purpose of this study is to review the general features of hydatidosis and to discuss atypical imaging characteristics of the complicated hydatid disease in the human, with an emphasis on structure and rupture of the cystic lesion as well as ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI) features of the disease. In our study, the available literature and images of the cases with complicated hydatidosis involving liver, lung, brain, spine and orbit were reviewed retrospectively. In hydatid disease, there are many potential local and systemic complications due to secondary involvement in almost any anatomic location in humans. Radiologically, in addition to the presence of atypical findings such as perifocal edema, non-homogenous contrast enhancement, multiplicity or septations and calcification, various unusual manifestations due to rupture or infection of the cyst have been observed in our cases with complicated hydatid disease. To prevent subsequent acute catastrophic results and the development of recurrences in various organs, it should be kept in mind that complicated hydatid cysts can cause unusual USG, CT, and MRI findings, in addition to typical ones, in endemic areas. Therefore, familiarity with atypical radiological appearances of complicated hydatid disease may be valuable in making a correct diagnosis and treatment. PMID- 17275239 TI - Quantitative determination of disaccharide content in digested unfragmented heparin and low molecular weight heparin by direct-infusion electrospray mass spectrometry. AB - Heparins and low molecular weight heparins (LMWHs) are heterogeneous glycosaminoglycans derived from natural sources that are prescribed as anticoagulants. In this work, a direct-infusion electrospray ionization mass spectrometry (ESI-MS) method was applied to the quantitative analysis of known disaccharides in various native heparins and LMWHs after digestion with heparinase enzymes. Disaccharide deltaUA2S-->GlcNS6S was found to compose the majority of all samples analyzed (81-88%). The values were significantly higher than those reported by previously published methods. The disaccharide isomer pair deltaUA-->GlcNS6S/deltaUA2S-->GlcNS was also detected in all samples at lower levels (11-19%). While digestion with heparinases I and II revealed a limited number of disaccharides, the addition of heparinase III to digests led to the detection of disaccharide deltaUA2S-->GlcNAc6S in native porcine heparin. This result indicated the importance of utilizing all three heparinases to gain maximum information when analyzing heparin and LMWH digests. This method displayed good between-day (4-6%) and between-digest (1-2%) reproducibility in separate experiments. To determine if the digestion matrix was suppressing the signal of low-abundance disaccharides, several disaccharides were exogenously added at low levels (1-10 pmol/mg) to a quenched digest reaction. Analysis revealed that low level disaccharides were detectable in this matrix above the limits of detection (0.1-0.2 pmol/mg) and quantitation (0.2-0.7 pmol/mg). While this method was unable to distinguish between disaccharide isomers, it utilized simple mass spectrometry instrumentation to provide useful quantitative data for characterizing preparations of native heparin and LMWH, which could be used to compare various marketed preparations of these popular anticoagulants. PMID- 17275240 TI - Development and application of a validated HPLC method for the determination of gabapentin and its major degradation impurity in drug products. AB - A simple isocratic reversed-phase HPLC method for the determination of gabapentin and its major degradation impurity, 3,3-pentamethylene-4-butyrolactam, was developed and validated for use in the analysis of pharmaceutical tablets and capsules. Separation was achieved on a Brownlee Spheri-5 Cyano column using an acetonitrile-10 mM KH2PO4/10 mM K2HPO4 (pH 6.2) (8:92, v/v) mobile phase. The compounds were eluted isocratically at a flow rate of 1 mL/min. Both compounds were analyzed with UV detection at 210 nm. The method was validated according to USP Category I requirements for gabapentin and USP Category II for 3,3 pentamethylene-4-butyrolactam. The validation characteristics included accuracy, precision, linearity, range, specificity, limit of quantitation and robustness. Validation acceptance criteria were met in all cases. This method was used successfully for the quality assessment of four gabapentin drug products. PMID- 17275241 TI - Simultaneous determination of lithospermic acid B and its three metabolites by liquid chromatography/tandem mass spectrometry. AB - A rapid and sensitive method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed for the simultaneous determination of lithospermic acid B and its three main O-methylated metabolites in rat serum with silibinin as the internal standard. The calibration curves for LSB, and the three metabolites were linear over the ranges of 16-4096, and 8-2048 ng/ml, respectively, with coefficients of correlation >0.998. For LSB, the intra-assay coefficient of variance (CV) was less than 9.3% and the inter-assay CV was less than 8.9%. The inter-assay mean accuracy was between 92.8% and 104.7%. For the three metabolites, the intra-assay CV was less than 8.7% and the inter-assay CV was less than 9.9%. The inter-assay mean accuracy was between 92.5% and 107.9%. This quantitation method was successfully applied to a pharmacokinetic study of LSB in rats. Also, a total recovery of 5.2% was found in bile after oral administration. PMID- 17275242 TI - Functional role of lingual nerve in breastfeeding. AB - Functional role of lingual nerve in breastfeeding was investigated in rat pups during the suckling period. DiI, a postmortem neuronal tracer, was used to confirm the immature lingual nerve (LN) responsible for tongue sensation and resulted in successful fiber labeling anterogradely to the tongue, which showed different distribution patterns from fiber labeling derived from the hypoglossal nerve. Unilaterally LN-injured pups did not show suckling disturbance with absence of any shortening (P11 pups: 559+/-16s; 105% of the control value) in nipple attachment time and the survival rate remained high (P11: 100%). Bilaterally LN-injured pups showed suckling disturbance with marked shortening (P11 pups: 220+/-54 s; 42% of the control value) in nipple attachment time and a low survival rate (P1: 33%; P11: 41%). Bilaterally infraorbital nerve-injured or bilaterally bulbectomized pups did not show any nipple attachment at all and there were no survivors, confirming the crucial roles of upper lip sensation and olfaction in suckling. Based on these findings, we conclude that tongue sensation is very important, but not essential for suckling. PMID- 17275243 TI - Reducing endogenous estrogen during development alters hormone production by porcine Leydig cells and seminiferous tubules. AB - High levels of estrogen produced by boar testes and the presence of estrogen receptors in both interstitial and tubular compartments are consistent with a direct role for estrogen in regulation of testicular cell function. This study investigated the importance of estrogen on hormone production by Leydig cells and seminiferous tubules in the developing boar. Thirty-six 1-week-old littermate pairs of boars were treated weekly with vehicle or 0.1 mg/kg BW Letrozole, an aromatase inhibitor, until castration at 2, 3, 4, 5, 6, 7, or 8 months. Tissue was collected and Leydig cells and seminiferous tubules were isolated. In a separate study, five untreated boars (ages 1.5-4 months) were castrated and Letrozole was added in vitro to Leydig cell and seminiferous tubule cultures. Leydig cells were cultured for 24h with and without porcine LH. Media were assayed for estradiol (E(2)) and testosterone (T) concentrations by RIA. Seminiferous tubules were cultured for 4h with and without porcine FSH; media were assayed for E(2) and immunoreactive inhibin (INH). In vivo aromatase inhibition decreased basal E(2) and increased basal T production by cultured Leydig cells. Basal seminiferous tubule production of E(2) but not INH was reduced. Decreasing estrogen synthesis in vivo did not alter LH-induced Leydig cell E(2) production or FSH-induced seminiferous tubule INH production. INH production decreased with advancing age regardless of treatment. In conclusion, in vivo aromatase inhibition altered baseline steroid production by cultured Leydig cells and seminiferous tubules but had little effect on response to gonadotropins. PMID- 17275244 TI - Progression of atherosclerosis in asymptomatic carotid arteries after contralateral endarterectomy: a 10-year prospective study. AB - OBJECTIVE: The best way to manage both symptomatic and asymptomatic severe carotid stenoses has been thoroughly demonstrated by large randomized clinical trials, but less is known about the natural history and management of the contralateral asymptomatic internal carotid artery (ICA). This prospective study was undertaken to determine whether disease progressed in the contralateral ICA of patients who had undergone carotid endarterectomy (CEA) and were followed up clinically and by duplex ultrasound (US) scan. METHODS: The contralateral asymptomatic ICAs of 599 patients who had undergone CEA for severe carotid disease over a 10-year period were followed up clinically and with duplex US scan at 1 month and then every 6 months. ICA stenosis was classified as mild (30% 49%), moderate (50%-69%), severe (70%-99%), or occlusion. Progression was defined as an increase in ICA stenosis of 50% or more for ICAs with a less than 50% baseline lesion or as an increase to a higher category if the baseline stenosis was 50% or more. End points of the study were the incidence of contralateral disease progression and late neurologic events. Kaplan-Meier analysis was used to estimate freedom from disease progression and from neurologic events. The relationship between progression and risk factors was also analyzed. RESULTS: Overall, disease progressed in 25.2% of patients (151/599) after a mean follow-up of 4.1 years. Disease progressed in 34.3% of patients (101/294) with mild stenosis vs 47.9% of patients with moderate stenosis (47/98; P = .016). Three additional patients with mild lesions at baseline progressed to severe lesions. The median time to progression was 29.8 months for mild and 18.5 months for moderate stenoses (P = .033). The rate of late neurologic events referable to the contralateral ICA was 3.2% (19/599) for the entire series and 4.8% (19/392) for patients with a 30% or greater ICA stenosis: these included 4 (0.7%) strokes and 15 (2.5%) transient ischemic attacks. All but 3 events (16.3%; 16/98) occurred in patients with disease progression from moderate to severe stenosis. Overall, 53 late CEAs were performed. CONCLUSIONS: This prospective analysis has shown that disease progression in contralateral asymptomatic ICAs after CEA is relatively common in patients with a diseased ICA at the baseline and strongly supports duplex US surveillance, approximately every 6 months, in patients with more than mild disease. A baseline lesion is significantly predictive of progression to severe stenosis, and progression from moderate to severe stenosis is strongly associated with neurologic clinical events. No demographic or clinical factor proved useful in identifying patients likely to experience disease progression. PMID- 17275245 TI - Technical modifications in endoscopic vein harvest techniques facilitate their use in lower extremity limb salvage procedures. AB - OBJECTIVE: We describe and report our results using endoscopic vein harvest (EVH) for lower extremity arterial bypass procedures, following the implementation of technical modifications specific to patients undergoing limb salvage procedures. METHODS: We underwent training in EVH, followed by implementation of the technique in patients requiring limb salvage for lower extremity ischemia and aneurysms. After technical modifications in the technique were developed for limb salvage, we reviewed our experience in all patients who underwent minimally invasive distal bypass with EVH. RESULTS: Technical modifications include limited arterial dissection before vein harvest, the use of proximal and distal leg incisions for both exposure of arterial vessels and saphenous vein harvest, improved hemostasis techniques in the vein graft tunnel, avoidance of compression wraps to the ipsilateral harvest tunnel, complete removal of the vein with either reversed or nonreversed graft placement, and use of the endoscopic tunnel for conduit placement. Thirteen patients (14 limbs) have undergone minimally invasive distal bypass since technical modifications were implemented. Indications for EVH were rest pain (n = 12; 85.7%) and tissue loss (n = 8; 57.1%). Veins harvested were the ipsilateral great saphenous vein (n = 10; 71.4%), contralateral great saphenous vein (n = 2; 14.3%), and short saphenous vein (n = 2; 14.3%). No venous injuries occurred during endoscopic harvest, and all were used for bypass. Thirty day primary and primary assisted patency rates were 85.7% and 92.9%, respectively. The limb salvage rate was 100%. Two patients developed postoperative hematomas, one early and one late, as a result of anticoagulation for cardiac comorbidities. Both patients required reoperation for successful re establishment of patency. There were no perioperative deaths and no postoperative wound infections or complications. Two patients required a later prosthetic bypass, and two required a vein graft angioplasty. Complete wound healing was achieved in 75% of patients with preoperative tissue loss. CONCLUSIONS: Technical modifications in endoscopic saphenous vein harvest techniques facilitate their use in lower extremity limb salvage procedures. Vascular surgeons should become familiar with these techniques to minimize vein harvest wound complications and extend the options for limb salvage conduits, including use of both the ipsilateral and contralateral saphenous vein and the short saphenous vein. Meticulous hemostasis within the tunnel after endoscopic conduit harvest and avoidance of postoperative anticoagulation should help to prevent postoperative hematoma formation and early graft occlusion. PMID- 17275246 TI - Hemodynamic impairment, venous segmental disease, and clinical severity scoring in limbs with Klippel-Trenaunay syndrome. AB - BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a complex congenital anomaly featuring two or more of the following: (1) capillary malformations (port-wine stains), (2) soft tissue or bony hypertrophy (or both), and (3) varicose veins or venous malformations. With the purpose of determining the actual significance of venous impairment in patients with KTS, we quantified the venous valvular competency and calf muscle pump function and examined their effect on clinical severity. METHODS: Included were patients with near-normal function of affected limb(s) and minimal/small foot hypertrophy. Excluded were those with deep venous hypoplasia, aplasia or thrombosis, lymphedema, limb length discrepancy (>2.5 cm), peripheral arterial (ankle-brachial index <1.0), or cardiac disease and walking impairment. Venous duplex scanning, ascending venography, magnetic resonance imaging, strain gauge plethysmography, and a bone scanogram were performed. We studied eight men and seven women aged 15 to 51 years (median, 24 years). The KTS involved 17 limbs (unilateral in 13 patients and bilateral in 2). Contralateral limbs in patients with unilateral KTS acted as controls (n = 13). Venous clinical severity was graded according to the CEAP and venous clinical severity score (VCSS), and reflux complexity was classified according to the venous segmental disease score. Outflow obstruction (outflow fraction at 1 and 4 seconds; OF(1) and OF(4), respectively), reflux (venous filling index), calf muscle pump function (ejection fraction), and hypertension (residual volume fraction) were determined in both limbs with strain gauge plethysmography. Data, reported as median and interquartile range, were analyzed with the Mann-Whitney test. RESULTS: Varicose veins or venous malformations occurred in the medial, posterior, or anterolateral limb segments of the ankle (7/17, 7/17, and 9/17), calf (10/17, 8/17, and 12/17), knee (9/17, 8/17, and 8/17), and thigh (10/17, 6/17, and 8/17, respectively). Venous malformations occupied the subcutaneous space (17/17) and extended into the subfascial space in 6 (35.3%) of 17 limbs. Abnormal reflux (>0.5 seconds) was distributed in the great (64.7%; 11/17) and small (5.9%; 1/17) saphenous veins and the common femoral (23.5%; 4/17), femoral (41.1%; 7/17), popliteal (29.4%; 5/17), perforator (70.6%; 12/17), and axial calf (35.3%; 6/17) veins. There was no difference in the OF(1) and OF(4) between the affected limbs and the controls. Limbs with KTS had a fivefold greater venous filling index (0.133-0.46 mL . 100 mL(-1) . s(-1); 0.258 mL . 100 mL(-1) . s(-1)) than the controls (0.034-0.055 mL . 100 mL(-1) . s(-1); 0.046 mL . 100 mL(-1) . s(-1); P < .0001), and this was linked to a higher venous segmental disease score (3 [2-4] vs 0 [0-1]; P < .0001). Limbs with KTS had half the ejection fraction (20.8%; 12.3%-24%) of the controls (39.3%; 30.9%-64.6%) and twice as high a residual venous fraction (77% [69.6%-84.5%] vs 40.9% [20.6%-60%]; both P < .004). Patients complained of swelling (100%; 15/15), aching (100%; 15/15), pain (93.3%; 14/15) and heaviness (100%; 15/15), tiredness (66.7%; 10/15), and tightness (33.3%; 5/15) of the limb(s) with KTS. Limbs with KTS had a worse (1) venous clinical severity by 11 VCSS points (11 [8-12] vs 0 [0-1]) and (2) clinical status by 3 CEAP classes (C3 [C3-C4] vs C0 [C0-C2]) than the control limbs (both P < .0001). CONCLUSIONS: Venous disease in limbs with KTS is a major source of morbidity in affected patients. Limbs with KTS are characterized by complex reflux patterns, severe valvular incompetence, calf muscle pump impairment, and venous hypertension, thus explaining the advanced clinical severity (VCSS) and CEAP grade. PMID- 17275247 TI - Mid-term outcomes of endovascular popliteal artery aneurysm repair. AB - OBJECTIVE: This study documents mid-term outcomes of a series of endovascular popliteal aneurysm repairs compared with concurrent results of open surgical repair. METHODS: A retrospective chart review was done of all popliteal artery aneurysm repairs since January 1, 2000. Patency was defined as continued presence of palpable pulses or maintenance of postoperative ankle-brachial index +/- 0.15. Statistical methods included chi(2), t test, Fisher's exact test, and Kaplan Meier plots with log-rank comparison. RESULTS: A total of 56 popliteal artery aneurysm repairs were performed. All endovascular popliteal aneurysm repairs (EVPAR, n = 15) were performed using Viabahn endoprostheses. Patients with open repair (OR, n = 41) underwent surgical bypass and aneurysm exclusion with great saphenous vein (n = 26), short saphenous vein (n = 3), or polytetrafluoroethylene (n = 12), through either a medial (n = 28) or posterior (n = 13) approach. All urgent cases received open repair. Technical success was 100% in both groups. Mean follow-up was 16.5 +/- 3 months (range, 0.5 to 56 months). Aneurysm size, location, and outflow were similar between groups. Primary patency, secondary patency, and survival did not differ between groups. Endoleaks were observed in three (20%) of 15 endovascular cases, and type I and III endoleaks were treated with additional endografts. CONCLUSION: To our knowledge, this represents the largest United States series of EVPAR to date. Early mid-term results of elective endovascular repair of popliteal artery aneurysms are encouraging. Further studies are warranted to define optimal indications for EVPAR and to generate long-term outcomes for this technique. PMID- 17275248 TI - Prospective evaluation of electroencephalography, carotid artery stump pressure, and neurologic changes during 314 consecutive carotid endarterectomies performed in awake patients. AB - OBJECTIVE: This study attempted to correlate neurologic changes in awake patients undergoing carotid endarterectomy (CEA) under cervical block anesthesia (CBA) with electroencephalography (EEG) and measurement of carotid artery stump pressure (SP). METHODS: Continuous EEG and SP monitoring was measured prospectively in 314 consecutive patients undergoing CEA between April 1, 2003, and July 30, 2006, under CBA. Indications for CEA were asymptomatic 70% to 99% internal carotid artery stenosis in 242 (77.1%), transient ischemic attacks (including transient monocular blindness) in 45 (14.3%), and prior stroke in 27 (8.6%). Mean common carotid artery pressure before clamping, mean SP after carotid clamping, and intraarterial pressure were continuously monitored in all patients. An indwelling shunt was placed when neurologic events (contralateral motor weakness, aphasia, loss of consciousness, or seizures) occurred, regardless of SP or EEG changes. RESULTS: Shunt placement was necessary because of neurologic changes in 10% (32/314) of all CEAs performed under CBA. Only 3 patients (1.4%) of 216 required shunt placement if SP was 50 mm Hg or more, vs 29 (29.6%) of 98 if SP was less than 50 mm Hg (P < .00001; sensitivity, 29.8%; specificity, 98.6%). In patients with SP of 40 mm Hg or more, 7 (2.6%) of 270 required shunt placement, vs 25 (56.8%) of 44 if SP was less than 40 mm Hg (P < .00001; sensitivity, 56.8%; specificity, 97.4%). Ischemic EEG changes were observed in 19 (59.4%) of 32 patients (false-negative rate, 40.6%) requiring shunt placement under CBA. Three patients had false-positive EEG results and did not require shunt placement (false-positive rate, 1.0%). The perioperative stroke/death rate was 4 (1.2%) in 314. All strokes occurred after surgery and were unrelated to cerebral ischemia or lack of shunt placement. CONCLUSIONS: Ten percent of patients required a shunt placement during CEA under CBA. Shunt placement was necessary in 56.8% of patients with SP less than 40 mm Hg. EEG identified cerebral ischemia in only 59.4% of patients needing shunt placement, with a false-positive rate of 1.0% and a false-negative rate of 40.6%. Both SP and EEG as a guide to shunt placement have poor sensitivity. Intraoperative monitoring of the awake patients under regional anesthesia (CBA) is the most sensitive and specific method to identify patients requiring shunt placement. PMID- 17275249 TI - Reduction of plasma taurine level in children affected by osteogenesis imperfecta during bisphosphonate therapy. AB - Osteogenesis imperfecta (OI) is a heritable disease of connective tissue characterized by increased bone fragility. To date, bisphosphonates seem to be the most promising therapy, at least for children. In the last decade experimental and clinical studies indicate that several amino acids are implicated in bone mineralization. Particularly, taurine is localized in matrices of the bone and can regulate osteoblast metabolism with antiosteopenic effect. To investigate a possible interaction between pharmacological effects of bisphosphonates and amino acids involved in bone metabolism, we performed plasma and urine amino acids analysis in children affected by OI before and during treatment with bisphosphonates. Fourteen prepubertal children with moderate to severe types of OI, 8 males and 6 females, aged from 2 to 11 years (mean (SD) 6.9+/-2.53) were enrolled in the study. Patients were treated with neridronate infusion (1mg/kg/body weight) every three months. Plasma and urine specimens for amino acid analysis were kept at baseline (T0) and three months after each infusion of four consecutive cycles (T1-T4). A significant decrease in respect to the pre-treatment levels (T0) was observed after the fourth infusion for taurine (p<0.01). In addition, urinary excretion of this amino acid showed a significant decrease after the fourth infusion. No significant correlations were found between plasma level or urinary excretion of hydroxyproline, taurine, arginine and lysine in respect to bone mineral density. The progressive reduction of plasma taurine found in our patients treated with bisphosphonates could be implicated in the action mechanism of this drug in OI and possibly in other disorders of bone metabolism. This knowledge could provide new opportunities to improve treatment with bisphosphonates and address novel strategies for the therapeutic approach to bone disorders. PMID- 17275250 TI - Suppressive effect of post- or pre-treatment of aspirin metabolite on mitomycin C induced genotoxicity using the somatic mutation and recombination test in Drosophila melanogaster. AB - In our previous paper, we found that aspirin suppressed in a somatic mutation and recombination test (SMART) of mitomycin C (MMC) in Drosophila melanogaster. In order to reveal the mechanism of bio-antimutagenicity and/or preventive effect of aspirin, we evaluated the suppressive ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA) and 2,3-dihydroxybenzoic acid (DHBA), in SMART in D. melanogaster using post- and pre-treatments. As for the post-treatment, SA reduced the numbers of large single and twin spots. GA reduced the small single and large single spots, and GUA reduced the single spots, large single and twin spots. The inhibition of GUA is slightly stronger than that of any other metabolites; the inhibition percentage is 49 at the dose of 5 mg/bottle. On the other hand, as for the pre treatment, aspirin, SUA, GA and DHBA reduced the numbers of small single spots. SUA, GE and DHBA reduced the number of large single spots. Aspirin and its metabolites did not reduce the number of twin spots. The results of the present study suggest that SA, GA and GUA repair or replicate DNA-damage by MMC and SUA, GA, GUA and DHBA prevent DNA-damage by MMC. It is suggested that secondary cancer is prevented by aspirin post-treatment without losing the medicinal effectiveness (anti-tumor activity). Therefore, we consider there are effective doses and/or administration timing of aspirin and MMC to prevent secondary cancer. PMID- 17275251 TI - [Meta-analyses or megatrials: same level of proof?]. AB - Results of meta-analyses may differ from those of megatrials only because of the bias that could be introduced by a unadequate methodology of some meta-analyses. A meta-analysis must be based on an exhaustive review of the literature - of all studies, those with negative as well as positive results. The quality of a meta analysis depends on the methodological quality of the studies it analyzes; accordingly they must be selected according to strict methodological inclusion and exclusion criteria, defined a priori. The value of a meta-analysis is that allows a treatment strategy to be assessed in populations more heterogeneous than those in clinical trials. Nonetheless the heterogeneity of protocols, of dosing, and of outcome measures can lead to bias of the treatment effect estimation. Different analytic techniques must be used to assess possible publication or selection bias (the so-called "funnel plot" method) and potential sources of heterogeneity (heterogeneity test, meta-regression, etc.). Meta-analyses of individual data make it possible to assess the treatment effect according to patient characteristics. Prospective meta-analyses or those planned before clinical trials can help to limit data heterogeneity by making study protocols less varied (treatment, follow-up, evaluation, etc.). PMID- 17275252 TI - Panic attacks and physical health problems in a representative sample: singular and interactive associations with psychological problems, and interpersonal and physical disability. AB - BACKGROUND: Panic attacks may be a risk marker for a variety of psychological problems and are associated with increased impairment in a host of domains. However, previous studies have not investigated the role of physical illness in the panic attack-disability relations, which is striking due to findings that physical illness is linked to both panic attacks and disability. The present investigation examined the singular and interactive effects of panic attacks and physical illness in relation to psychological, interpersonal, and physical types of impairment. METHOD: Adult participants (4,745) recruited from the statewide Colorado Social Health Survey were administered the diagnostic interview schedule. RESULTS: As predicted, main effects of panic attacks and physical illness were significantly related to psychiatric comorbidity, depressive symptoms, interpersonal functioning, physical functioning, and perceived general health (p<.05 for all associations). Also as predicted, interaction of panic attacks and physical illness was significantly related to all of the outcome variables (p<.05 for all associations). CONCLUSIONS: These findings suggest that individuals with both panic attacks and physical illness experience elevated disability across a variety of dimensions. PMID- 17275253 TI - The role of drinking motives in social anxiety and alcohol use. AB - Although social anxiety and problem drinking commonly co-occur, the relationship between social anxiety and drinking among college students is not well understood. The current study examined the relationship between drinking motives, or reasons for drinking, and social anxiety in 239 volunteers. Contrary to hypotheses, high (n=83), moderate (n=90), and low (n=66) social anxiety groups did not differ in endorsement of coping and conformity drinking motives. Further, social anxiety was negatively related to weekly alcohol use and unrelated to alcohol-related problems. Post hoc hierarchical multiple regression analyses conducted for each social anxiety group indicated that coping motives were related to greater alcohol use and problems for those in the high and moderate social anxiety groups, but not for the low social anxiety group. It appears that drinking motives, particularly coping motives, have promise in providing a greater understanding of the social anxiety-drinking relationship. Drinking motives could aid in identification of socially anxious students at risk for alcohol problems and inform intervention strategies. PMID- 17275255 TI - Role of IL-1 and TNF in the brain: twenty years of progress on a Dr. Jekyll/Mr. Hyde duality of the innate immune system. AB - The immune-privileged status of the central nervous system (CNS) has changed quite dramatically during the past two decades. Leukocytes have the ability to infiltrate the CNS and cytokines are produced by resident cells, especially during injuries and diseases. Although the cellular source and role of these immune ligands are better known, their exact contribution to brain protection, repair or diseases still remains highly debated today. The ultimate fate of the immune reaction depends on the cytokines involved and the experimental models. It is now generally accepted that microglia play a central role in this response, at least for the production of cytokines participating in the innate immune system. As macrophages, resident microglia produce numerous cytokines and two of them have been largely studied since the beginning of this field of research. Twenty years ago, interleukin 1 (IL-1) and tumor-necrosis factor (TNF) were cloned and recombinant forms were used to investigate their functions ranging from normal neurophysiological responses to pathological conditions. This review presents the history of these two cytokines during immune responses in the brain and where we are now two decades later. PMID- 17275254 TI - Examining information processing biases in spider phobia using the rapid serial visual presentation paradigm. AB - Empirical research has demonstrated the existence of attentional biases towards threat in anxiety disorders. Paradigms commonly used to assess attentional biases have failed to demonstrate consistent findings as well as reveal the specific features of attentional biases. The current study investigated the utility of the rapid serial visual presentation paradigm in assessing attentional biases among 40 undergraduate students with high spider phobia (SP) symptoms and 40 undergraduate students with low SP symptoms. Results revealed that across participants, threatening information was processed in a facilitated and automatic manner and resulted in an immediate (i.e., within 120 ms) attentional capture. Following immediate attentional capture, however, only high SP participants exhibited an attentional alertness towards subsequent stimuli following threat presentation. These results extend traditional attentional bias literature, and theoretical implications are discussed. PMID- 17275256 TI - Multilayer perceptron tumour diagnosis based on chromatography analysis of urinary nucleosides. AB - Nucleosides in human urine are of interest as a biochemical marker for cancer, acquired immune deficiency syndrome (AIDS) and the whole-body turnover of RNAs. A reversed-phase high-performance liquid chromatography (RP-HPLC) method with photodiode-array detection was used to quantitatively analyze urinary normal and modified nucleosides. 55 persons with malignant tumors of various types, 13 persons with benign tumors and 41 healthy controls were investigated within a clinical intervention study. Artificial neural networks (ANN) have been used as a practical pattern recognition tool to distinguish cancer patients from healthy persons. Using a multilayer perceptron (MPL), a specificity of 85%, and a sensitivity of 97% in differentiation between tumor patients and healthy persons was achieved. The differentiation between benign and malignant tumors had a sensitivity of 60% and a specificity of 84%. These results verify the usefulness of ANN and the RP-HPLC method for tumor recognition in agreement with existing studies. PMID- 17275257 TI - Critical role for lipid raft-associated Src kinases in activation of PI3K-Akt signalling. AB - Lipid rafts are membrane microdomains distinct from caveolae, whose functions in polypeptide growth factor signalling remain unclear. Here we show that in small cell lung cancer (SCLC) cells, specific growth factor receptors such as c-Kit associate with lipid rafts and that these domains play a critical role in the activation of phosphoinositide 3-kinase (PI3K) signalling. The class IA p85/p110alpha associated with Src in lipid rafts and was activated by Src in vitro. Lipid raft integrity was essential for Src activation in response to stem cell factor (SCF) and raft disruption selectively inhibited activation of protein kinase B (PKB)/Akt in response to SCF stimulation. Moreover, inhibition of Src kinases blocked PKB/Akt activation and SCLC cell growth. The use of fibroblasts with targeted deletion of the Src family kinase genes confirmed the role of Src kinases in PKB/Akt activation by growth factor receptors. Moreover a constitutively activated mutant of Src also stimulated PI3K/Akt in lipid rafts, indicating that these microdomains play a role in oncogenic signalling. Together our data demonstrate that lipid rafts play a key role in the activation of PI3K signalling by facilitating the interaction of Src with specific PI3K isoforms. PMID- 17275258 TI - Metastasizing ameloblastoma. AB - Ameloblastomas are locally invasive tumours of odontogenic origin with a high propensity for local recurrence. Regional and distant metastases are extremely rare. Here is presented a case of a 26-year-old woman with a recurrent ameloblastoma of the mandible and a metastatic lymph node in the homolateral neck. PMID- 17275260 TI - Nasal implants following nasectomy. AB - A case of a 63-year-old female who was reconstructed with an implant-supported nasal prosthesis following nasectomy is reported. The technique and advantages of this treatment modality are discussed. PMID- 17275259 TI - Effect of calcitonin on bone regeneration in male rats: a histomorphometric analysis. AB - The aim of this study was to evaluate the effectiveness of calcitonin in promoting bone growth in surgical bone defects in rat mandibles. Fifty male rats were divided into two groups: bone defect (control) and bone defect with calcitonin (experimental). A circular bone defect 4mm in diameter was made in the mandibular bone of the rats in the angle region, and covered with a polytetrafluoroethylene barrier. The experimental group received 2 IU/kg of synthetic salmon calcitonin intramuscularly three times a week, with treatment starting immediately after surgery. The animals were killed 3, 7, 14, 21 and 28 days after the surgical procedure. The bone defects were examined histologically and by histomorphometric analysis. The Student t-test was applied to the histomorphometric data, with the level of significance set at 5%. The animals of the experimental group showed a lower level of bone formation at almost all time points than the control group, but no difference between groups was observed 28 days after surgery. The volume of newly formed bone matrix was significantly greater in the control than the experimental group at 7, 14 and 21 days, as determined by both morphologic and histomorphometric analysis. Bone repair in the calcitonin-treated animals was delayed in comparison to controls, indicating the need for further studies on male rats. PMID- 17275261 TI - Fertility of first-degree relatives of patients with schizophrenia: a three generation perspective. AB - We explored the fertility in three generations; fertility of parents, siblings and offspring to patients with schizophrenia, to test the hypothesis that the decreased reproductive rate in the patients is compensated by an increased rate in their first-degree relatives. A population-based national database was created by linking the Swedish Multi-Generation and Hospital Discharge Registers. To maximize follow-up time for schizophrenia and reproductive history, three birth cohorts were selected: parental generation, born 1918-1927 (n=274464); affected generation, born 1932-1941 (n=108502) and offspring to affected generation, born 1951-1960 (n=103105). Ratios of estimated mean number of offspring were measured (fertility ratios), comparing the study subjects to the general population. The fertility among males with schizophrenia was decreased by over 70% (fertility ratio(patients/population)=0.29, 95% CI 0.25-0.35), whereas female patients had less than half as many offspring as the general female population (fertility ratio(patients/population)=0.48, 95% CI 0.42-0.55). When accounting for selection bias of larger families, no statistically significant difference was found among parents of patients with and without a diagnosis of schizophrenia. Further, the fertility among siblings of schizophrenic patients did not differ from the general population. A reduction in fertility was found among offspring to patients with schizophrenia, male offspring had 12% fewer offspring (fertility ratio(offspring/population)=0.88, 95%CI 0.77-1.01), while female offspring had 6% fewer offspring (fertility ratio(offspring/population)=0.94, 95% CI 0.84-1.05). In conclusion, we found reduced fertility in patients with schizophrenia and among their offspring that was not compensated by higher parental or sibling fertility. PMID- 17275262 TI - Bactericidal properties of silica particles with silver islands located on the surface. PMID- 17275263 TI - Antiviral effect of a synthetic brassinosteroid on the replication of vesicular stomatitis virus in Vero cells. AB - The antiviral mode of action of the synthetic brassinosteroid (22S,23S)-3beta bromo-5alpha,22,23-trihydroxystigmastan-6-one (6b) against replication of vesicular stomatitis virus (VSV) in Vero cells was investigated. Time-related experiments showed that 6b mainly affects a late event of the virus growth cycle. Virus adsorption, internalisation and early RNA synthesis are not the target of the inhibitory action. Results obtained indicate that the antiviral compound adversely affects virus protein synthesis and viral mature particle formation. PMID- 17275264 TI - The anti-inflammatory activity of telithromycin in a mouse model of septic shock. PMID- 17275265 TI - Characterisation of plasmids encoding CTX-M-3 extended-spectrum beta-lactamase from Enterobacteriaceae isolated at a university hospital in Taiwan. AB - CTX-M-3 is the most common extended-spectrum beta-lactamase produced by Enterobacteriaceae in Taiwan. The present study was conducted to characterise the genetic environment surrounding bla(CTX-M-3). A total of 11 ceftriaxone-resistant isolates were studied: Escherichia coli (n=4), Klebsiella pneumoniae (n=5) and Salmonella enterica serotypes Anatum (SA831R) and Potsdam (SC72). Molecular methods used included polymerase chain reaction, sequencing, DNA-DNA hybridisation, conjugation, physical mapping and restriction fragment length polymorphism (RFLP) analysis. All isolates examined carried bla(CTX-M-3) on large plasmids (>70kb). The resistance plasmids of the two Salmonella and two K. pneumoniae strains (KP104 and KP116) were confirmed to be conjugative in vitro. RFLP analysis indicated that the plasmids were different. Physical mapping also revealed the difference between the two Salmonella plasmids, pSA831R (82kb) and pSC72 (74kb). An insertion sequence, ISEcp1, was found upstream of each bla(CTX-M 3) gene. However, sequencing of downstream regions of the bla genes showed two different patterns: the presence of orf477 in pSA831R and of orf1-mucA in pSC72, pKP104 and pKP116. IncI1-type oriT and nikA sequences were present in the plasmids of all the clinical isolates tested, except S. Anatum. Different bla(CTX M-3)-carrying plasmids were identified among the enterobacteria studied. The presence of ISEcp1 in all isolates may be associated with the widespread resistance among Enterobacteriaceae. Although the plasmids were not identical, they appeared to belong to the same incompatibility group (IncI1-like plasmids), suggesting that they are genetically related but may have evolved divergently over time. PMID- 17275266 TI - Augmented reinforcer value and accelerated habit formation after repeated amphetamine treatment. AB - Various processes might explain the progression from casual to compulsive drug use underlying the development of drug addiction. Two of these, accelerated stimulus-response (S-R) habit learning and augmented assignment of motivational value to reinforcers, could be mediated via neuroadaptations associated with long lasting sensitization to psychostimulant drugs, i.e. augmented dopaminergic neurotransmission in the striatum. Here, we tested the hypothesis that both processes, which are often regarded as mutually exclusive alternatives, are present in amphetamine-sensitized rats. Amphetamine-sensitized rats showed increased responding for food under a random ratio schedule of reinforcement, indicating increased incentive motivational value of food. In addition, satiety specific devaluation experiments under a random interval schedule of reinforcement showed that amphetamine-sensitized animals exhibit accelerated development of S-R habits. These data show that both habit formation and motivational value of reinforcers are augmented in amphetamine-sensitized rats, and suggest that the task demands determine which behavioral alteration is most prominently expressed. PMID- 17275268 TI - XPS investigation of DNA binding to zirconium-phosphonate surfaces. AB - The surface coverage of phosphorylated oligonucleotides immobilized on a zirconium-phosphonate surface was analyzed using X-ray photoelectron spectroscopy (XPS). By quantifying the intensity of the N 1s signal originating from the oligonucleotide and the Zr 3d peak from the metal-phosphonate surface, the surface coverage of the oligonucleotide could be calculated with a modified substrate-overlayer model. We found relatively low surface coverages indicating that once covalently bound via the terminal phosphate the polymer chain further physisorbs to the surface limiting the adsorption of additional molecules. PMID- 17275267 TI - Infrared spectroscopy studies of cation effects on lipopolysaccharides in aqueous solution. AB - The conformation of amphiphilic lipopolysaccharides (LPS) influences the behavior of free and cell-bound LPS in aqueous environments, including their adhesion to surfaces. Conformational changes in Pseudomonas aeruginosa serotype 10 LPS aggregates resulting from changes in solution pH (3, 6, and 9), ionic strength [I] 1, 10, and 100 mmol L(-1), and electrolyte composition (NaCl and CaCl(2)) were investigated via attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy. ATR-FTIR data indicate that LPS forms more stable aggregates in NaCl relative to CaCl(2) solutions. Time- and cation-dependent changes in ATR-FTIR data suggest that LPS aggregates are perturbed by Ca(2+) complexation at lipid A phosphoryl groups, which leads to reorientation of the lipid A at the surface of a ZnSe ATR internal reflection element (IRE). Polarized ATR-FTIR investigations reveal orientation of LPS dipoles approximately perpendicular to the IRE plane for both Na- and Ca-LPS. The results indicate that changes in solution chemistry strongly impact the conformation, intermolecular and interfacial behavior of LPS in aqueous systems. PMID- 17275269 TI - Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE. AB - We aimed to increase the efficiency of adenoviral vectors by limiting adenoviral spread from the target site and reducing unwanted host immune responses to the vector. We complexed adenoviral vectors with DDAB-DOPE liposomes to form adenovirus-liposomal (AL) complexes. AL complexes were delivered by intratumoral injection in an immunocompetent subcutaneous rat tumor model and the immunogenicity of the AL complexes and the expression efficiency in the tumor and other organs was examined. Animals treated with the AL complexes had significantly lower levels of beta-galactosidase expression in systemic tissues compared to animals treated with the naked adenovirus (NA) (P<0.05). The tumor to non-tumor ratio of beta-galactosidase marker expression was significantly higher for the AL complex treated animals. NA induced significantly higher titers of adenoviral-specific antibodies compared to the AL complexes (P<0.05). The AL complexes provided protection (immunoshielding) to the adenovirus from neutralizing antibody. Forty-seven percent more beta-galactosidase expression was detected following intratumoral injection with AL complexes compared to the NA in animals pre-immunized with adenovirus. CONCLUSIONS: Complexing of adenovirus with liposomes provides a simple method to enhance tumor localization of the vector, decrease the immunogenicity of adenovirus, and provide protection of the virus from pre-existing neutralizing antibodies. PMID- 17275270 TI - High-amylose carboxymethyl starch matrices for oral sustained drug-release: in vitro and in vivo evaluation. AB - High-amylose corn starch, that contains 70% of amylose chains and 30% of amylopectin, has been used to obtain substituted amylose (SA) polymers. Tablets have been prepared by direct compression, i.e. dry mixing of drug and SA, followed by compression, which is the easiest way to manufacture an oral dosage form. Until now, their controlled-release properties have been assessed only by an in vitro dissolution test. Amylose-based polymers are normally subject to biodegradation by alpha-amylase enzymes present in the gastrointestinal tract, but matrix systems show no significant degradation of tablets by alpha-amylase in vitro. High-amylose sodium carboxymethyl starch (HASCA) is an interesting excipient for sustained drug-release in solid oral dosage forms. In addition to the easy manufacture of tablets by direct compression, the results show that in vitro drug-release from an optimized HASCA formulation is not affected by either acidic pH value or acidic medium residence time. In addition, a compressed blend of HASCA with an optimized quantity of sodium chloride provides a pharmaceutical sustained-release tablet with improved integrity for oral administration. In vivo studies demonstrate extended drug absorption, showing that the matrix tablets do not disintegrate immediately. Nevertheless, acetaminophen does not seem to be the most appropriate drug for this type of formulation. PMID- 17275271 TI - The role of food restriction on CCl4-induced cirrhosis model in rats. AB - Effects of food restriction on susceptibility to the toxic effect of some chemicals are controversial. In order to identify an exposure model that could maximize cirrhosis and minimize mortality rate, this study aimed to evaluate the effect of food restriction on tetrachloride carbon (CCl(4))-induced cirrhosis model in rats. Fifty-three male Wistar rats received CCl(4) 0.25 ml/kg weekly intragastrically once a week. Thirty-three had 44% food restriction (group 1); 10 rats had 25% food restriction (group 2); and 10 rats received ad libitum food (group 3). After 10 weeks, the animals were sacrificed and liver sections were collected for histology. Of the 53 animals enrolled for the study, 22 (41.5%) died before completing 10-week CCl(4). Mortality rate was significantly higher in group 1 compared to other groups (p<0.05). Cirrhosis was significantly more prevalent in group 1 than in group 3 (p<0.01), but without significant difference between groups 1 and 2 (p=0.624). We concluded that food restriction is an important issue to be considered when establishing a CCl(4)-induced cirrhosis model in rats. Moreover, there is an ideal range of food intake that predisposes to liver damage without increasing mortality leading to a more effective model. PMID- 17275272 TI - Thyroid hormone induces myocardial matrix degradation by activating matrix metalloproteinase-1. AB - Hyperthyroid patients develop left ventricular hypertrophy associated with alterations of several cardiac parameters such as heart rate, cardiac output, cardiac contraction and hemodynamic overload leading to cardiac complications. Although cardiac hypertrophy and contractile abnormality occur, interstitial fibrosis in the heart usually does not take place in hyperthyroid condition. Therefore, in the present study, the mechanism regulating myocardial extracellular matrix (ECM) remodeling in hyperthyroid condition was investigated. Cardiac hypertrophy was developed in Sprague-Dawley rats by administration of 3,5,3'-triiodo-L-thyronine (triiodothyronine, 8 microg/100g BW, ip, SID) and glucocorticosteroid, dexamethasone (DEX, 35 microg/100g BW, po, SID), which is also an inducer of hypertrophy for 15 days. Heart/Body weight ratio and atrial and brain natriuretic peptide mRNAs were significantly increased in both triiodothyronine- and DEX-treated rats compared to control. Collagens-I and -III deposition in the left ventricular sections was reduced in triiodothyronine treated rats, whereas in DEX-treated animals those were increased compared to control. While mRNA and protein levels of procollagens-I and -III were increased with triiodothyronine (p<0.01), the levels of mature collagens-I and -III were decreased. The levels of the mature collagens were increased with DEX compared to control. MMP-1 activity in the serum and left ventricle was higher with reduced levels of TIMPs-3 and -4 in the left ventricle of triiodothyronine-treated rats. The results suggest that accelerated breakdown of collagens-I and -III by MMP-1 due to suppression of the endogenous TIMPs plays an important role in regulating the ECM in myocardium of hyperthyroid rat. PMID- 17275273 TI - Protective effect of n-3 polyunsaturated fatty acids concentrate on isoproterenol induced myocardial infarction in rats. AB - The protective effect of PUFA concentrate prepared from fish oil on isoproterenol induced myocardial infarction in male albino rats was investigated with respect to changes in the levels of diagnostic marker enzymes, cholesterol, triglycerides, free fatty acids, phospholipids, reduced glutathione (GSH) and lipid peroxides (LPO). Administration of PUFA concentrate significantly prevented the isoproterenol-induced elevation in the levels of plasma diagnostic marker enzymes (ALT [93.5%], AST [95.6%], LDH [94.7%] and CPK [96.1%]). PUFA concentrate feeding exerted a significant antilipidemic effect against isoproterenol-induced myocardial infarction by reducing the levels of lipid components in plasma (cholesterol [71.5%], triglycerides [79.7%] and free fatty acids [70.7%] and heart tissue (cholesterol [81.4%], triglycerides [76.3%] and free fatty acids [78.6%]). A tendency to prevent the isoproterenol-induced phospholipids depletion (74.4%) in the myocardium of experimental rats was also observed. The level of lipid peroxidation was also found to be significantly lower in PUFA treated animals (2.72+/-0.15nmol/ml in plasma; 1.18+/-0.08nmol/mg protein in heart tissue) as compared to that of isoproterenol-injected groups (5.77+/-0.43nmol/ml in plasma; 2.14+/-0.15nmol/mg protein in heart tissue) of rats. Also the level of reduced GSH significantly higher in the heart tissue of PUFA administered experimental rats (5.65+/-0.98 microg/g) as compared to myocardial infarction induced control rats (2.39+/-0.18 microg/g). The results of the present study indicate that the overall cardioprotective effect of PUFA concentrate is probably related to its ability to inhibit lipid accumulation by its hypolipidaemic property. PMID- 17275274 TI - Failure of conjugated linoleic acid supplementation to enhance biosynthesis of docosahexaenoic acid from alpha-linolenic acid in healthy human volunteers. AB - A rate-limiting step in docosahexaenoic acid (DHA) formation from alpha-linolenic acid (ALA) involves peroxisomal oxidation of 24:6n-3 to DHA. The aim of the study was to determine whether conjugated linoleic acid (CLA) would enhance conversion of ALA to DHA in humans on an ALA-supplemented diet. The subjects (n=8 per group) received daily supplementation of ALA (11g) and either CLA (3.2g) or placebo for 8 weeks. At baseline, 4 and 8 weeks, blood was collected for plasma fatty acid analysis and a number of physiological measures were examined. The ALA supplemented diet increased plasma levels of ALA and eicosapentaenoic acid (EPA). The addition of CLA to the ALA diet resulted in increased plasma levels of CLA, as well as ALA and EPA. Plasma level of DHA was not increased with either the ALA alone or ALA plus CLA supplementation. The results demonstrated that CLA was not effective in enhancing DHA levels in plasma in healthy volunteers. PMID- 17275275 TI - Direct glucose determination in blood using a reagentless optical biosensor. AB - This paper demonstrates that glucose determination in blood can be done directly (without sample pretreatment) using a reagentless reversible biosensor based on the intrinsic spectroscopic properties of peroxidase (HRP). The biosensor, prepared by HRP and glucose oxidase entrapment in a polyacrylamide gel matrix, works in continuous mode, presents a linear response range from 1.5 x 10(-6) up to 5.5 x 10(-5)M and can be used for at least 750 measurements; in the best conditions (0.1 M pH 6 phosphate buffer, HRP and GOx amounts in the polymersation mixture for the sensor film preparation 0.0165 and 0.0010 g, respectively) the minimum samples rate is 30 h(-1). For glucose determination, blood is simply diluted in water (until haemolysis is completed) and fed into the sensor without a cleaning step between samples; the blood absorption is corrected in a simple way by working at a proper reference wavelength. The biosensor signals have been mathematically modeled in order to facilitate the design of sensors based on the same idea for other biochemical compounds. PMID- 17275276 TI - Yeasts in foods and beverages: impact on product quality and safety. AB - The role of yeasts in food and beverage production extends beyond the well-known bread, beer and wine fermentations. Molecular analytical technologies have led to a major revision of yeast taxonomy, and have facilitated the ecological study of yeasts in many other products. The mechanisms by which yeasts grow in these ecosystems and impact on product quality can now be studied at the level of gene expression. Their growth and metabolic activities are moderated by a network of strain and species interactions, including interactions with bacteria and other fungi. Some yeasts have been developed as agents for the biocontrol of food spoilage fungi, and others are being considered as novel probiotic organisms. The association of yeasts with opportunistic infections and other adverse responses in humans raises new issues in the field of food safety. PMID- 17275277 TI - Imaging apoptosis for detecting plaque instability: rendering death a brighter facade. AB - The relatively poor correlation between the risk of atherosclerotic plaque rupture and the degree of luminal obstruction before this event implies a strong imperative for in vivo detection of the processes underlying progressive plaque destabilization. In addition to the morphologic characteristics, apoptosis and inflammation comprise two important indicators of plaque instability. Apoptotic macrophage death results in enlargement of the plaque necrotic core and positive vascular remodelling, whereas apoptosis of the smooth muscle cells leads to attenuation of the fibrous cap. Imaging of apoptotic cells with annexin A5 provides an opportunity for the non-invasive assessment of cell death, and hence plaque vulnerability. The clinical detection of apoptosis could therefore promote the development of novel intervention strategies. PMID- 17275278 TI - Charcot-Marie-Tooth disease: peripartum management of two contrasting clinical cases. AB - Charcot-Marie-Tooth disease is a rare hereditary motor and sensory demyelinating polyneuropathy with potentially severe and debilitating peripheral symptoms. Respiratory muscles and vertebral anatomy can be affected, both of which may have significant impact on any planned or unplanned anaesthetic intervention during labour. We describe two cases at opposite ends of a wide spectrum of disease severity. The first case illustrates an approach to the management of a mildly affected patient who was permitted to labour normally, but nevertheless needed a detailed antenatal plan in order to allay her anxiety and prepare for potentially complicated labour analgesia and operative delivery. Spontaneous delivery of a healthy infant did not require anaesthetic intervention during labour. The second woman had severe scoliosis and marked respiratory impairment and required non invasive ventilatory support for one week before scheduled caesarean section. A single-shot spinal anaesthetic was used as a spinal catheter could not be sited. This produced a high block for which a brief period of respiratory assistance was required. Perioperative management and subsequent high dependency care are discussed. PMID- 17275279 TI - General anaesthesia and Caesarean section for a patient with hereditary spastic paraparesis (Strumpell's disease). PMID- 17275280 TI - Influence of epidural analgesia on labor in mid and late termination of pregnancy: an observational study. PMID- 17275281 TI - Acute fatty liver of pregnancy; three cases and discussion of analgesia and anaesthesia. AB - Acute fatty liver of pregnancy is a rare, potentially fatal, complication of late pregnancy. The incidence is estimated at 1:7000-1:15000 pregnancies. Presentation is classically with malaise, nausea and vomiting, abdominal pain and rarely encephalopathy. Prolongation of laboratory clotting tests is an early feature. Ultrasound examination of the liver is performed to exclude biliary stasis. Rapid clinical deterioration may occur and urgent delivery should be organised. Anaesthetists form part of a multidisciplinary approach before, during and after delivery but there are few reports of anaesthetic involvement. One dilemma facing an anaesthetist called to assist in these cases is the potentially negative effect of general anaesthesia on hepatic encephalopathy versus the risks associated with regional anaesthesia in the presence of coagulopathy. Postoperative analgesia may also be complicated by impaired renal and hepatic function. We present three cases that occurred in our unit in a 6-month period illustrating the spectrum of disease severity and the successful use of different anaesthetic techniques to facilitate management including delivery. PMID- 17275282 TI - Prevention of postoperative nausea and vomiting after intrathecal morphine for Cesarean section: a randomized comparison of dexamethasone, droperidol, and a combination. AB - BACKGROUND: Intrathecal morphine provides good analgesia after cesarean delivery but the side effects include nausea and vomiting. Low-dose droperidol (0.625 mg) combined with dexamethasone 4 mg is postulated to have an additive antiemetic effect with less side effects. We therefore compared single doses of dexamethasone and droperidol alone with a low-dose combination of the two, to prevent spinal morphine-induced nausea and vomiting after cesarean section. METHODS: In a double-blind study, 120 women undergoing elective cesarean section under spinal anesthesia (using 0.5% bupivacaine 10 mg and morphine 0.2 mg) were allocated randomly to receive dexamethasone 8 mg, droperidol 1.25 mg, dexamethasone 4 mg and droperidol 0.625 mg, or placebo, before the end of surgery. The incidences of nausea and vomiting, sedative score, pain score, and side effects were recorded. RESULTS: The incidence of nausea and vomiting within 6 h postoperatively was lower and incidence of no nausea and vomiting for 24 h postoperatively was significantly higher for the combination group compared to the placebo group and the dexamethasone only group. Sedation scores within 3 h postoperatively and incidence of restlessness for the combination group were significantly lower than in the droperidol only group. CONCLUSION: An additive antiemetic effect and no significant side effects were shown for the combination of dexamethasone 4 mg and droperidol 0.625 mg. This combination was more effective than either dexamethasone 8 mg or droperidol 1.25 mg alone in preventing nausea and vomiting after spinal anesthesia using 0.5% bupivacaine and morphine 0.2 mg. PMID- 17275283 TI - Autism spectrum disorders: developmental disconnection syndromes. AB - Autism is a common and heterogeneous childhood neurodevelopmental disorder. Analogous to broad syndromes such as mental retardation, autism has many etiologies and should be considered not as a single disorder but, rather, as 'the autisms'. However, recent genetic findings, coupled with emerging anatomical and functional imaging studies, suggest a potential unifying model in which higher order association areas of the brain that normally connect to the frontal lobe are partially disconnected during development. This concept of developmental disconnection can accommodate the specific neurobehavioral features that are observed in autism, their emergence during development, and the heterogeneity of autism etiology, behaviors and cognition. PMID- 17275285 TI - Molecular mechanisms of autism: a possible role for Ca2+ signaling. AB - Autism spectrum disorders (ASDs) are a group of developmental disorders characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. The molecular mechanisms that underlie ASDs are not known, but several recent developments suggest that some forms of autism are caused by failures in activity-dependent regulation of neural development. Mutations of several voltage-gated and ligand gated ion channels that regulate neuronal excitability and Ca2+ signaling have been associated with ASDs. In addition, Ca2+-regulated signaling proteins involved in synapse formation and dendritic growth have been implicated in ASDs. These recent advances suggest a set of signaling pathways that might have a role in generating these increasingly prevalent disorders. PMID- 17275284 TI - Neurexin-neuroligin signaling in synapse development. AB - Neurexins and neuroligins are emerging as central organizing molecules for excitatory glutamatergic and inhibitory GABAergic synapses in mammalian brain. They function as cell adhesion molecules, bridging the synaptic cleft. Remarkably, each partner can trigger formation of a hemisynapse: neuroligins trigger presynaptic differentiation and neurexins trigger postsynaptic differentiation. Recent protein interaction assays and cell culture studies indicate a selectivity of function conferred by alternative splicing in both partners. An insert at site 4 of beta-neurexins selectively promotes GABAergic synaptic function, whereas an insert at site B of neuroligin 1 selectively promotes glutamatergic synaptic function. Initial knockdown and knockout studies indicate that neurexins and neuroligins have an essential role in synaptic transmission, particularly at GABAergic synapses, but further studies are needed to assess the in vivo functions of these complex protein families. PMID- 17275286 TI - Commissure formation in the mammalian forebrain. AB - Commissural formation in the mammalian brain is highly organised and regulated both by the cell-autonomous expression of transcription factors, and by non-cell autonomous mechanisms including the formation of midline glial structures and their expression of specific axon guidance molecules. These mechanisms channel axons into the correct path and enable the subsequent connection of specific brain areas to their appropriate targets. Several key findings have been made over the past two years, including the discovery of novel mechanisms of action that 'classical' guidance factors such as the Slits, Netrins, and their receptors have in axon guidance. Moreover, novel guidance factors such as members of the Wnt family, and extracellular matrix components such as heparan sulphate proteoglycans, have been shown to be important for mammalian brain commissure formation. Additionally, there have been significant discoveries regarding the role of FGF signalling in the formation of midline glial structures. In this review, we discuss the most recent advances in the field that have contributed to our current understanding of commissural development in the telencephalon. PMID- 17275288 TI - Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice. AB - 1alpha,25-Dihydroxyvitamin D(3) [1,25D] deficiency and vitamin D receptor [VDR] genotypes are risk factors for several diseases and disorders including heart diseases. Extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases [MMPs] contributes to progressive left ventricular remodeling, dilation, and heart failure. In the present study, we used high-density oligonucleotide microarray to examine gene expression profile in wild type [WT] and vitamin D receptor knockout mice (VDR KO) which was further validated by RT PCR. Microarray analysis revealed tissue inhibitors of metalloproteinases [TIMP-1 and TIMP-3] were significantly under expressed in VDR KO mice as compared to WT mice which was further validated by RT-PCR. Zymography and RT-PCR showed that MMP 2 and MMP-9 were up regulated in VDR KO mice. In addition, cross-sectional diameter and longitudinal width of the VDR KO heart myofibrils showed highly significant cellular hypertrophy. Trichrome staining showed marked increase in fibrotic lesions in the VDR KO mice. Heart weight to body weight ratio showed approximately 41% increase in VDR KO mice when compared to WT mice. This data supports a role for 1,25D in heart ECM metabolism and suggests that MMPs and TIMPs expression may be modulated by vitamin D. PMID- 17275289 TI - Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. AB - Our previous studies showed vitamin D deficiency results in increased cardiac contractility, hypertrophy and fibrosis and has profound effects on heart proteomics, structure and function in rat. In this study we found that the heart in vitamin D receptor knockout (VDR-KO) mice is hypertrophied. Six homozygous VDR knockout (-/-), six wild type (+/+) and six heterozygous (+/-) mice were fed a diet containing 2% Ca, 1.25% P and 20% lactose to maintain normal blood calcium and phosphate levels for 12 months. Tail-cuff blood pressure was performed on all mice. Blood pressure determinations showed no differences in systolic or mean blood pressure in WT (+/+), KO (-/-) or HETERO (+/-) mice at 3 and 6 months. However, decreased systolic BP in the KO mice relative to WT at 9 months of age was observed. ECG analysis showed no significant differences in the intact KO, HETERO or WT mice. The mice were killed at 12 months. Heart weight/body weight ratio was 41% (P<.003) greater in the KO mice versus WT and HETERO was 19% (P<.05) increased versus WT. Other VDR-KO tissues did not display hypertrophy. Cross sectional and longitudinal analysis of the heart myofibrils showed highly significant cellular hypertrophy in VDR-KO mice. Trichrome staining of heart tissue showed marked increase in fibrotic lesions in the KO mice. Analysis of plasma renin activity, angiotensin II (AII) and aldosterone levels showed elevated but not significantly different renin activity in KO versus WT and no significant differences in AII or aldosterone levels. Our data do not support the concept that the renin-angiotensin system or hypertension are the factors that elicit these changes. Data presented here reveal that ablation of the VDR signaling system results in profound changes in heart structure. We propose that calcitriol acts directly on the heart as a tranquilizer by blunting cardiomyocyte hypertrophy. PMID- 17275290 TI - The role of ThinPrep cytology in the investigation of lung tumors. AB - AIMS OF THE STUDY: The aim of this study was to evaluate the role of liquid-based cytology with the ThinPrep (TP) (Cytyc; Cytyc, Co, Boxborough, MA, USA) technique, using fine-needle aspiration (FNA) for sampling, in the investigation of suspicious pulmonary lesions. METHODS: We performed percutaneous computed tomography (CT)-guided FNA biopsy of focal pulmonary lesions in 80 adult patients. Study subjects were all consecutive patients and potential candidates for surgery. The sample was then examined by both conventional smears (CS) and TP techniques. TP smears of all FNA were prepared from needle rinsing obtained following preparation of CS. All cytological diagnoses were correlated with the CS and/or thoracotomy histological diagnoses in order to evaluate the role of liquid-based cytology with the TP technique. RESULTS: Using TP technique diagnosis was successfully established in 75 patients out of 80, whereas using CS cytology diagnosis was established in 54 patients (p<0.001, z=3899). Inadequate material was observed in 5 cases (6.25%) with the TP technique and in 13 cases (16.25%) with the CS technique (z=-2.77, p<0.05). CONCLUSIONS: We believe that the TP technique has a good overall yield for the diagnosis of suspicious for malignant lung lesions. We found that the accuracy of determining lung cancer was excellent. PMID- 17275291 TI - Study on biomethonization of waste water from jam industries. AB - Anaerobic digestion of wastewater from jam industries was studied in a continuous reactor with different organic loading rates (OLR) and the optimum organic loading rate was 6.5 kg COD/m(3)/day when it was operated with three days HRT. The biodegradability of wastewater in batch experiments was about 90%. The removal efficiency of total COD and soluble COD were found to 82% and 85%, respectively. The specific methane production was 0.28 m(3)/kg of COD removed/day. PMID- 17275292 TI - The effects of olive mill waste compost and poultry manure on the availability and plant uptake of nutrients in a highly saline soil. AB - The effects of a compost (produced from by-products of the olive oil industry) and a poultry manure on mineral ion solubility and exchangeability in a highly saline agricultural soil (electrical conductivity for a 1:5 soil:water extract=1.85 dS m(-1)) from Murcia (SE Spain) were studied. The organic amendments did not change significantly the soil electrical conductivity or the soluble Na(+), Ca(2+) or Mg(2+). Only soluble K(+) increased, due to the K(+) supplied by the amendments. The cation exchange capacity increased in treated soils, the exchange complex being mainly saturated with Ca(2+), Mg(2+) and K(+). However, Na(+) was not retained in the exchange sites, and the sodium absorption ratio remained low. The compost and manure increased markedly the shoot growth of the salt-tolerant Beta maritima L. (sea beet) and Beta vulgaris L. (sugar beet). For B. maritima, this seemed to be related to decreases in the shoot concentrations of Na(+) and Cl(-) and increases in K(+) and H(2)PO(4)(-). In the case of B. vulgaris, increases in shoot H(2)PO(4)(-) and B and, for manure treated soil, a decrease in shoot Na(+) may have been involved. Cultivation of tomato (Lycopersicon esculentum Mill. cv. Moneymaker) in the soil used previously for B. vulgaris indicated that the effects of the manure on tissue cation concentrations were longer-lasting than those of the compost. PMID- 17275293 TI - N-caffeoylphenalkylamide derivatives as bacterial efflux pump inhibitors. AB - As part of an ongoing project to identify plant natural products as efflux pump inhibitors (EPIs), bioassay-guided fractionation of the methanolic extract of Mirabilis jalapa Linn. (Nyctaginaceae) led to the isolation of an active polyphenolic amide: N-trans-feruloyl 4'-O-methyldopamine. This compound showed moderate activity as an EPI against multidrug-resistant (MDR) Staphylococcus aureus overexpressing the multidrug efflux transporter NorA, causing an 8-fold reduction of norfloxacin MIC at 292 microM (100 microg/mL). This prompted us to synthesize derivatives in order to provide structure-activity relationships and to access more potent inhibitors. Among the synthetic compounds, some were more active than the natural compound and N-trans-3,4-O-dimethylcaffeoyl tryptamine showed potentiation of norfloxacin in MDR S. aureus comparable to that of the standard reserpine. PMID- 17275294 TI - A spectroscopic and molecular modeling study of sinomenine binding to transferrin. AB - Sinomenine, an herbal ingredient isolated from Sinomenium acutum, is used for the amelioration of arthritis. It has been found that this molecule could bind to human serum transferrin (Tf), the iron (III) transport protein in the blood, by using fluorescence, circular dichroism (CD) spectroscopy, and molecular modeling methods. The results provide possible usage of transferrin to transport sinomenine. PMID- 17275296 TI - Novel mitochondria-localizing TEMPO derivative for measurement of cellular oxidative stress in mitochondria. AB - Neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, and apoptosis, are thought to be associated with oxidative stress affecting mitochondria. In this study, we designed and synthesized a fluorescein-tagged TEMPO derivative, compound 1, with triphenylphosphino moiety. Synthesized 1 localized in mitochondria and detected oxidative stress in an endotoxic model of a mouse macrophage-like cell line. Compound 1 is therefore a potentially useful probe for evaluating oxidative stress in mitochondria. PMID- 17275295 TI - Synthesis and cytotoxic activity of 17-carboxylic acid modified 23-hydroxy betulinic acid ester derivatives. AB - New 17-carboxylic acid modified 23-hydroxy betulinic acid ester derivatives were prepared and tested for cytotoxic activity on five cancer cell lines in vitro: all tested compounds showed stronger cytotoxic activity than 23-hydroxy betulinic acid and betulinic acid. In addition, compound 5a was tested for anti-tumor activity in vivo: it had much better anti-tumor activity than 23-OH betulinic acid and had similar anti-tumor activity with cyclophosphamide and 5 fluorouracil. PMID- 17275297 TI - Synthesis and biological evaluation of unprecedented classes of spiro-beta lactams and azido-beta-lactams as acyl-CoA:cholesterol acyltransferase inhibitors. AB - Unprecedented classes of four- and five-membered hydroxyl-spiro-beta-lactams and hydroxyl-azido-beta-lactams were prepared via regioselective ring opening of hydroxyl-epoxides. The potential of these particular beta-lactams as biologically active compounds has been confirmed by the results obtained in ACAT inhibition assays. PMID- 17275298 TI - Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: exploration of core and headpiece structure-activity relationships. AB - A novel series of antiproliferative agents containing pyrazolo[1,5-a]pyrimidin-7 yl phenyl amides, selective for p21-deficient cells, were identified by high throughput screening. Exploration of the SAR relationships in the headpiece, core, and tailpiece is described. Strict steric, positional, and electronic requirements were observed, with a clear preference for both core nitrogens, a thienoyl headpiece, and meta substituted tailpiece. PMID- 17275299 TI - An oskar-dependent positive feedback loop maintains the polarity of the Drosophila oocyte. AB - The localization of oskar mRNA to the posterior of the Drosophila oocyte defines the site of assembly of the pole plasm, which contains the abdominal and germline determinants. oskar mRNA localization requires the polarization of the microtubule cytoskeleton, which depends on the recruitment of PAR-1 to the posterior cortex in response to a signal from the follicle cells, where it induces an enrichment of microtubule plus ends. Here, we show that overexpressed oskar mRNA localizes to the middle of the oocyte, as well as the posterior. This ectopic localization depends on the premature translation of Oskar protein, which recruits PAR-1 and microtubule-plus-end markers to the oocyte center instead of the posterior pole, indicating that Oskar regulates the polarity of the cytoskeleton. Oskar also plays a role in the normal polarization of the oocyte; mutants that disrupt oskar mRNA localization or translation strongly reduce the posterior recruitment of microtubule plus ends. Thus, oskar mRNA localization is required to stabilize and amplify microtubule polarity, generating a positive feedback loop in which Oskar recruits PAR-1 to the posterior to increase the microtubule cytoskeleton's polarization, which in turn directs the localization of more oskar mRNA. PMID- 17275300 TI - Specialization, constraints, and conflicting interests in mutualistic networks. AB - The topology of ecological interaction webs holds important information for theories of coevolution, biodiversity, and ecosystem stability . However, most previous network analyses solely counted the number of links and ignored variation in link strength. Because of this crude resolution, results vary with scale and sampling intensity, thus hampering a comparison of network patterns at different levels . We applied a recently developed quantitative and scale independent analysis based on information theory to 51 mutualistic plant-animal networks, with interaction frequency as measure of link strength. Most networks were highly structured, deviating significantly from random associations. The degree of specialization was independent of network size. Pollination webs were significantly more specialized than seed-dispersal webs, and obligate symbiotic ant-plant mutualisms were more specialized than nectar-mediated facultative ones. Across networks, the average specialization of animal and plants was correlated, but is constrained by the ratio of plant to animal species involved. In pollination webs, rarely visited plants were on average more specialized than frequently attended ones, whereas specialization of pollinators was positively correlated with their interaction frequency. We conclude that quantitative specialization in ecological communities mirrors evolutionary trade-offs and constraints of web architecture. This approach can be easily expanded to other types of biological interactions. PMID- 17275301 TI - Nonaccidental properties underlie shape recognition in Mammalian and nonmammalian vision. AB - An infinite number of 2D patterns on the retina can correspond to a single 3D object. How do visual systems resolve this ill-posed problem and recognize objects from only a few 2D retinal projections in varied exposure conditions? Theories of object recognition rely on the nonaccidental statistics of edge properties, mainly symmetry, collinearity, curvilinearity, and cotermination. These statistics are determined by the image-formation process (i.e., the 2D retinal projection of a 3D object ); their existence under a range of viewpoints enables viewpoint-invariant recognition. An important question in behavioral biology is whether the visual systems of nonmammalian animals have also evolved biases to utilize nonaccidental statistics . Here, we trained humans and pigeons to recognize four shapes. With the Bubbles technique, we determined which stimulus properties both species used to recognize the shapes. Both humans and pigeons used cotermination, the most diagnostic nonaccidental property of real world objects, despite evidence from a model computer observer that cotermination was not the most diagnostic pictorial information in this particular task. This result reveals that a nonmammalian visual system that is different anatomically from the human visual system is also biased to recognize objects from nonaccidental statistics. PMID- 17275303 TI - The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. AB - Podosomes and invadopodia are unique actin-rich adhesions that establish close contact to the substratum but can also degrade components of the extracellular matrix. Accordingly, matrix degradation localized at podosomes or invadopodia is thought to contribute to cellular invasiveness in physiological and pathological situations. Cell types that form podosomes include monocytic, endothelial and smooth muscle cells, whereas invadopodia have been mostly observed in carcinoma cells. This review highlights important new developments in the field, discusses the common and divergent features of podosomes and invadopodia and summarizes current knowledge about matrix-degrading proteinases at these structures. PMID- 17275302 TI - Hyphal orientation of Candida albicans is regulated by a calcium-dependent mechanism. AB - Eukaryotic cells from fungal hyphae to neurites that grow by polarized extension must coordinate cell growth and cell orientation to enable them to exhibit growth tropisms and to respond to relevant environmental cues. Such cells generally maintain a tip-high Ca(2+) cytoplasmic gradient, which is correlated with their ability to exhibit polarized tip growth and to respond to growth-directing extracellular signals. In yeast and other fungi, the polarisome, exocyst, Arp2/3, and Spitzenkorper protein complexes collectively orchestrate tip growth and cell polarity, but it is not clear whether these molecular complexes also regulate cell orientation or whether they are influenced by cytoplasmic Ca(2+) gradients. Hyphae of the human pathogenic fungus Candida albicans reorient their growth axis in response to underlying surface topography (thigmotropism) and imposed electric fields (galvanotropism). The establishment and maintenance of directional growth in relation to these environmental cues was Ca(2+) dependent. Tropisms were attenuated in media containing low Ca(2+), or calcium-channel blockers, and in mutants where calcium channels or elements of the calcium signaling pathway were deleted. Therefore galvanotropism and thigmotropism may both be mediated by localized Ca(2+) influx at sites of polarized growth via Ca(2+) channels that are activated by appropriate environmental signals. PMID- 17275304 TI - Nonapoptotic functions of caspases: caspases as regulatory molecules for immunity and cell-fate determination. AB - Caspases are a family of cysteine proteases that are highly conserved in multicellular organisms and function as central regulators of apoptosis. Recent investigations in Caenorhabditis elegans, Drosophila and mice suggest that caspases also function as regulatory molecules for immunity and cell-fate determination. Here, we review genetic studies of nonapoptotic functions of caspases and discuss the regulatory mechanisms of caspases for executing nonapoptotic functions. PMID- 17275305 TI - An electromyographic analysis of obligatory (hemiplegic cerebral palsy) and voluntary (normal) unilateral toe-walking. AB - This study compares lower extremity muscle activation during gait in patients with hemiplegic cerebral palsy (CP) with healthy subjects mimicking the patients. The purpose was to understand the differences between obligatory toe-walking as observed in hemiplegic CP gait and voluntary toe-walking. The results contribute to a better understanding by distinguishing between primary deviations in muscle activity as a direct consequence of the underlying neurological pathology of hemiplegic CP and secondary, compensatory deviations due to the biomechanics of toe-walking. Surface electromyographic (EMG), kinematic and kinetic data were compared between a group of 12 hemiplegic CP patients and a group of 10 healthy subjects walking normally and when mimicking hemiplegic gait. Integrated 3D gait analysis was performed with simultaneous EMG recordings of the medial gastrocnemius, tibialis anterior, rectus femoris, and semitendinosus muscles bilaterally. The EMG pattern of the toe-walking leg in the mimicking subjects was modified in gastrocnemius and tibialis anterior as compared with normal gait. This modified muscle activation pattern showed strong similarities to that of the patients and therefore can be regarded, at least in part, as activity required for toe-walking. A possible primary gait abnormality was observed in the rectus femoris where the patients showed a burst of EMG activity in mid-swing phase in contrast to the mimicking subjects who showed normal EMG during this phase. PMID- 17275306 TI - Obstacle crossing in lower limb amputees. AB - OBJECTIVE: To study limitations in function and adjustment strategies in lower limb amputees during obstacle crossing. DESIGN: Observational cohort study. SUBJECTS: Transfemoral and transtibial amputees and able-bodied control subjects. METHODS: In a motion analysis laboratory unimpeded and obstacle crossing runs were performed. The subjects stepped over an obstacle of 0.1m height and thickness and 1m width. Outcome measures were gait velocity, hip, knee and ankle joint angles and leading limb preference. RESULTS: Whereas able-bodied and transtibial subjects demonstrated an increase in knee flexion during obstacle crossing compared to unimpeded walking, in transfemoral amputees the opposite was seen, namely a decrease in knee flexion. The lack of knee strategy in transfemoral amputees was compensated by circumduction at the hip on the prosthetic side and plantar flexion of the non-affected ankle. Transtibial amputees preferred to cross the obstacle with the prosthetic limb first, while transfemoral amputees preferred the non-affected limb. CONCLUSION: The different leading limb strategy in transfemoral and transtibial amputees could be explained by the restricted flexion and propulsion properties of the prosthetic knee. Training of obstacle crossing tasks during rehabilitation and improvement of prosthetic design may contribute to safe obstacle crossing. PMID- 17275307 TI - Using or abusing: viruses and the cellular DNA damage response. AB - During infection, viruses attempt to hijack the cell while the host responds with various defense systems. Traditional defenses include the interferon response and apoptosis, but recent work suggests that this antiviral arsenal also includes the cellular DNA damage response machinery. The observation of interactions between viruses and cellular DNA repair proteins has not only uncovered new complexities of the virus-host interaction but is also reinforcing the view that viruses can reveal key regulators of cellular pathways through the proteins they target. PMID- 17275308 TI - Wza: a new structural paradigm for outer membrane secretory proteins? AB - Gram-negative bacteria need to be able to transport a large variety of macromolecules across their outer membranes. In Escherichia coli, the passage of the group 1 capsular polysaccharide is mediated by an integral outer membrane protein, Wza. The crystal structure of Wza, determined recently, reveals a novel transmembrane alpha-helical barrel and a large central cavity within the core of the vase-shaped protein complex. The structure has similarities with that of the secretin protein, PilQ, which mediates the transition of type IV pili across the outer membrane. We propose that the large internal chamber, which can accommodate the secreted assembled macromolecule, is likely to be a common feature found in other outer membrane proteins involved in secretion processes. PMID- 17275309 TI - Peptidoglycan recognition proteins of the innate immune system. AB - Peptidoglycan (PGN) is the major component of bacterial cell walls and one of the main microbial products recognized by the innate immune system. PGN recognition is mediated by several families of pattern recognition molecules, including Toll like receptors, nucleotide-binding oligomerization domain-containing proteins, and peptidoglycan recognition proteins (PGRPs). However, only the interaction of PGN with PGRPs, which are highly conserved from insects to mammals, has so far been characterized at the molecular level. Here, we describe recent structural studies of PGRPs that reveal the basis for PGN recognition and provide insights into the signal transduction and antibacterial activities of these innate immune proteins. PMID- 17275310 TI - Exploration into the spatial and temporal mechanisms of bacterial polarity. AB - The recognition of bacterial asymmetry is not new: the first high-resolution microscopy studies revealed that bacteria come in a multitude of shapes and sometimes carry asymmetrically localized external structures such as flagella on the cell surface. Even so, the idea that bacteria could have an inherent overall polarity, which affects not only their outer appearance but also many of their vital processes, has only recently been appreciated. In this review, we focus on recent advances in our understanding of the molecular mechanisms underlying the establishment of polarized functions and cell polarity in bacteria. PMID- 17275311 TI - Outcome of and prognostic factors for decompressive hemicraniectomy in malignant middle cerebral artery infarction. AB - Decompressive hemicraniectomy as an appropriate treatment for malignant middle cerebral artery (MCA) infarction is still a controversial issue. This study aimed to determine the survival rate and functional outcome, and factors associated with these, in patients with malignant MCA infarction. From January 2000 to December 2003, 60 patients with malignant MCA infarction were treated in our hospital. All patients in the study underwent a large ipsilateral craniectomy and duroplasty for decompression. The infarction territory was evaluated by either diffusion weighted magnetic resonance imaging or computed tomography. Clinical neurological presentation was evaluated using the Glasgow Coma Scale. Functional outcome was evaluated using the Barthel index (BI) and the Glasgow Outcome Scale (GOS) at follow-up 12 months later. Thirty-day mortality was 20% (12 patients) and 12-month mortality was 26.6%. The factors associated with higher mortality were age>or=60 years, involvement of more than one vascular territory, presence of signs indicating clinical herniation before surgery, and treatment more than 24 hours after ictus. The mean GOS score was 3.3+/-1.7. The mean Barthel index was 65.1+/-40.1. Twenty-nine (65.9%) patients had a favourable outcome (BI>or=60). The factors associated with favourable outcome were age<60 years and treatment within 24 hours of ictus, before clinical signs of herniation were noted. Decompressive hemicraniectomy should be performed in patients younger than 60 years within 24 hours of ictus before clinical signs of herniation develop. Age, timing of surgery and clinical signs of herniation are prognostic factors for mortality and functional outcome. PMID- 17275312 TI - Synthesis, pharmacological evaluation and electrochemical studies of novel 6 nitro-3,4-methylenedioxyphenyl-N-acylhydrazone derivatives: Discovery of LASSBio 881, a new ligand of cannabinoid receptors. AB - We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio 881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity. PMID- 17275314 TI - Matrix metalloproteinases (MMPs): chemical-biological functions and (Q)SARs. AB - Matrix metalloproteinases (MMPs) are a large family of calcium-dependent zinc containing endopeptidases, which are responsible for the tissue remodeling and degradation of the extracellular matrix (ECM), including collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan. They are regulated by hormones, growth factors, and cytokines, and are involved in ovarian functions. MMPs are excreted by a variety of connective tissue and pro-inflammatory cells including fibroblasts, osteoblasts, endothelial cells, macrophages, neutrophils, and lymphocytes. These enzymes are expressed as zymogens, which are subsequently processed by other proteolytic enzymes (such as serine proteases, furin, plasmin, and others) to generate the active forms. Matrix metalloproteinases are considered as promising targets for the treatment of cancer due to their strong involvement in malignant pathologies. Clinical/preclinical studies on MMP inhibition in tumor models brought positive results raising the idea that the development of strategies to inhibit MMPs may be proved to be a powerful tool to fight against cancer. However, the presence of an inherent flexibility in the MMP active-site limits dramatically the accurate modeling of MMP-inhibitor complexes. The interest in the application of quantitative structure-activity relationships (QSARs) has steadily increased in recent decades and we hope it may be useful in elucidating the mechanisms of chemical-biological interactions for this enzyme. In the present review, an attempt has been made to explore the in-depth knowledge from the classification of this enzyme to the clinical trials of their inhibitors. A total number of 92 QSAR models (44 published and 48 new formulated QSAR models) have also been presented to understand the chemical-biological interactions. QSAR results on the inhibition of various compound series against MMP-1, -2, -3, -7, -8, -9, -12, -13, and -14 reveal a number of interesting points. The most important of these are hydrophobicity and molar refractivity, which are the most important determinants of the activity. PMID- 17275313 TI - Syntheses and anti-cancer activities of 2-[1-(indol-3-yl-/pyrimidin-5-yl /pyridine-2-yl-/quinolin-2-yl)-but-3-enylamino]-2-phenyl-ethanols. AB - Schiff bases prepared by the reactions of substituted amines with indole-/, pyrimidine-/, pyridine-/, and quinoline-aldehydes are made to undergo indium mediated allylation whereby a (substituted amine, allyl)methyl group has been introduced at C-3 of indole, C-5 of pyrimidine, and C-2 of pyridine and quinoline. Amongst the 16 compounds investigated for anti-cancer activities at 59 human tumor cell lines 3, 9-12, and 14 show appreciable activities. The structure activity relationship studies point that the contribution of phenylglycinol moiety as a part of side chain at C-3 of indole and C-5 of pyrimidine seems to be crucial for exhibiting anti-cancer activities. PMID- 17275315 TI - Synthesis, structure, and estrogenic activity of 4-amino-3-(2 methylbenzyl)coumarins on human breast carcinoma cells. AB - A number of coumarins exhibit interesting pharmacological activities and are therefore of therapeutic use. We report here the synthesis and the structural analysis of new N-substituted 4-amino-3-(2-methylbenzyl)coumarins (compounds 8a 8e) that present structural analogies with estrothiazine and 11- or 7-substituted 17beta-estradiol. These derivatives were tested with respect to estrogenic activity on the estrogen receptor positive (ER+) human MCF-7 breast cancer cell line. Two of the reported compounds (8a and 8b) stimulated specifically the proliferation of MCF-7 cells, but not that of estrogen receptor negative (ER-) human MDA-MB-231 breast cancer cells, suggesting that their mitogenic activity is mediated by ER. Accordingly, the stimulating effect of 8a and 8b was suppressed by the pure antiestrogen fulvestrant. Besides, 8a and 8b induced ER down regulation similar to that produced by classical ER agonists or pure antagonists. The effects of the compounds under study on ER-mediated transcription were assessed on (ER+) MVLN cells, that is, MCF-7 cells stably transfected with a pVit tk-Luc reporter plasmid. Derivatives 8a and 8b, and surprisingly compound 8c, enhanced ER-mediated gene transactivation in that model. Finally, no coumarin was able to compete with tritiated 17beta-estradiol ([(3)H]E(2)) for ER binding, suggesting unconventional interactions with the receptor, such as interactions with the second binding pocket or with the coactivator-binding region. To conclude, observations performed in this study on compound 8c reveal that estrogenic activity can be dissociated from enhancement of cell proliferation. Furthermore, ERE-driven transactivation of transcription seems to be a condition necessary, but not sufficient, for estrogen-induced stimulation of cell growth. PMID- 17275316 TI - The effect of 5-substitution in the pyrimidine ring of dUMP on the interaction with thymidylate synthase: molecular modeling and QSAR. AB - Thymidylate synthase (TS) is a target enzyme for a number of anticancer agents including the 5-fluorouracil metabolite, FdUMP. The present paper reports on molecular modeling studies of the effect of substitution at C(5) position in the pyrimidine ring of the TS substrate, dUMP, on the binding affinity for the enzyme. The results of molecular dynamics simulations show that the binding of C(5) analogues of dUMP to TS in the binary complexes does not undergo changes, unless a substituent with a large steric effect, such as the propyl group, is involved. On the other hand, apparent differences in the binding of the TS cofactor, resulting from varying substitution at dUMP C(5), are observed in the modeled structures of the ternary complexes of TS. These binding characteristics are supplemented with a classical QSAR model quantifying the relation between the affinity for TS and the substituent electronic and steric effects of C(5) analogues of dUMP. Based on the findings from the present work, the perspectives for finding promising new C(5) analogues of dUMP as potential agents targeted against TS are discussed. PMID- 17275317 TI - Synthesis and structure-activity relationships of novel warfarin derivatives. AB - 4-Hydroxycoumarins such as warfarin 1 have been the mainstay of oral anticoagulation therapy for over 20 years. Yet little detail is known about the molecular interactions between 4-hydroxycoumarins with vitamin K epoxide reductase (VKER), inhibition of which produces a deficiency of vitamin K and consequently a deficiency of vitamin K-dependent proteins involved in thrombus formation. Using molecular probes, such as 4-sulfhydrylwarfarin 7 and 4 chlorowarfarin 10 it is shown in vitro that inhibition of VKER by warfarin is dependent on deprotonation of the 4-hydroxycoumarin moiety. In addition, the nature of the substituent on carbon 3 of the 4-hydroxycoumarin modulated inhibition. More specifically, a linear isoprenyl side chain increased inhibition of VKER when compared to cyclical substituents as present in warfarin. An example of a 4-hydroxycoumarin with an isoprenyl side chain is the natural product ferulenol 19 derived from Ferula communis. Ferulenol 19 confers approximately 22 times more potent inhibition than warfarin and is approximately 1.5 more potent than the rodenticide brodifacoum in this in vitro assay. Based on these data it is hypothesized that 4-hydroxycoumarins bind to the active site of VKER thereby mimicking the transition state of the elimination of water from substrate 2 hydroxyvitamin K. PMID- 17275318 TI - Synthesis and biological activity of 2,5-diaryl-3-methylpyrimido[4,5-c]quinolin 1(2H)-one derivatives. AB - A series of 2,5-diaryl-3-methylpyrimido[4,5-c]quinolin-1(2H)-ones (7-30), variously substituted at the 2- and 5-phenyl moieties, were synthesized and evaluated for their in vitro cytotoxic activity against a PC3 cancer cell line. Cytotoxicity data revealed that the type of substituent as well as substitution pattern have variable influence on cytotoxic activity. Among the compounds tested, compounds (9), (13), (18), (19), and (23) demonstrated appreciable cytotoxic activity with mean IC(50) values of 2.0, 1.4, 1.6, 2.2, and 1.9microM, respectively. Methyl substitution at the 2-phenyl ring was found to yield the least active compounds. Two of the most potent compounds (13) and (18) were further investigated for inhibition of tubulin polymerization and found to have no activity at the concentrations used in the assay. PMID- 17275319 TI - Incidence of neurological complications following overstenting of the left subclavian artery. AB - OBJECTIVE: Aortic endovascular stent-graft implantation is associated with low morbidity and mortality rates. Overstenting of the left subclavian artery may be necessary to create a satisfactory proximal 'landing zone' for the stent-graft. Few cases have been published reporting adverse neurological events after overstenting of the left subclavian artery. We thus evaluated whether this procedure is associated with a higher rate of neurological complications by focusing on the management of the supra-aortic vessels. METHODS: Twenty patients suffering from aortic arch aneurysms (n=3), descending aortic aneurysms (n=7), acute (n=6) and chronic (n=4) type-B aortic dissections underwent stent-graft repair with complete (n=14) or partial (n=6) overstenting of the left subclavian artery. Three patients underwent overstenting of the entire aortic arch with ascending aortic-bi-carotid bypass grafting. One patient with right carotid and vertebral artery occlusion underwent initial carotid-to-subclavian bypass. All patients subsequently underwent neurological examination and Doppler ultrasound for detection of neurological and peripheral vascular complications. RESULTS: Aortic stent-graft repair was successful in all patients without acute neurologic complications. Two patients developed late central adverse neurological events: right-sided vertebral artery occlusion with brainstem infarction (n=1) and impaired binocular vision combined with dizziness (n=1), necessitating secondary subclavian transposition in one patient. Peripheral symptoms related to occlusion of the left subclavian artery were observed in five patients as sensory and motoric deficits of the left hand and arm. CONCLUSIONS: Overstenting of the left subclavian artery as treatment of aortic pathologies in high-risk patients is feasible but associated with the risk of neurological complications and peripheral symptoms. Side effects were mild or transient in most of our patients. Detailed preoperative exploration of vascular anatomy and pathology via Doppler ultrasound, CT- or MRI scan is mandatory to avoid adverse neurological events. Prior surgical revascularization of the left subclavian artery is essential in patients with high-grade stenoses, occlusions, or anatomic variants of the supra aortic branches. Delayed surgical revascularization is necessary only in patients with relevant subclavian steal syndrome or severe peripheral vascular symptoms. PMID- 17275321 TI - Female reproductive ageing: current knowledge and future trends. AB - Over the past few decades, postponement of childbearing has led to a decrease in family size and increased rates of age-related female subfertility. Age-related decrease in ovarian follicle numbers and a decay in oocyte quality dictate the occurrence of natural loss of fecundity and, ultimately, menopause. The rate of this ovarian ageing process is highly variable among women. Identification of women who have severely decreased ovarian reserve for their age is, therefore, clinically relevant. Endocrine and imaging tests for ovarian reserve relate mainly to the quantitative aspect of ovarian reserve, but their capacity to predict the chances for pregnancy is limited. Genetic factors regulating the size of the follicle pool and the rate of its depletion might be identified in the near future and, possibly, assist the accurate prediction of a woman's reproductive lifespan. PMID- 17275322 TI - Dynamic collision-induced dissociation (DCID) in a quadrupole ion trap using a two-frequency excitation waveform: I. Effects of excitation frequency and phase angle. AB - This study describes the application of a two-frequency excitation waveform to the end-cap electrodes of a quadrupole ion trap (QIT) during the mass acquisition period to deliberately fragment selected precursor ions. This approach obviates the need for a discrete excitation period and guarantees on-resonant excitation conditions without any requirement for resonant tuning; it is therefore faster than the conventional approach to collision-induced dissociation (CID) in QITs. The molecular ion of n-butylbenzene is used as thermometer molecule to determine the energetics of the new excitation procedure. The excitation waveform, consisting of two closely spaced sinusoidal frequencies, has an interference pattern that displays nodes and crests in the time domain. The energetics (determined by the product ion ratios of 91/92 Th) and CID efficiencies are highly dependent on the excitation amplitude, the relative position of the excitation frequencies in the Mathieu stability diagram, and whether the ions come into resonance during a node or crest of the excitation waveform. Under highly energetic conditions, ratios of 91/92 as large as 15 can be obtained at concomitant CID efficiencies of 10%, indicating internal energies in excess of 10 eV at the time of fragmentation. These extremely high internal energies far exceed the energetics achievable using conventional on-resonance excitation in QITs, indicating that the collisional heating rate is very fast in the new approach. Under less energetic conditions CID efficiencies as high as 70% are possible, which compares favorably with results obtained by conventional on resonance excitation. Correlation analyses are used to determine the conditions that simultaneously optimize energetic and efficient fragmentation conditions. PMID- 17275323 TI - TLR signaling. AB - The TLR family senses the molecular signatures of microbial pathogens, and plays a fundamental role in innate immune responses. TLRs signal via a common pathway that leads to the expression of diverse inflammatory genes. In addition, each TLR elicits specific cellular responses to pathogens owing to differential usage of intracellular adapter proteins. Recent studies have revealed the importance of the subcellular localization of TLRs in pathogen recognition and signaling. TLR signaling pathways is negatively regulated by a number of cellular proteins to attenuate inflammation. Here, we describe recent advances in our understanding of the regulation of TLR-mediated signaling. PMID- 17275324 TI - Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. AB - The Toll family of receptors consists of cell surface TLRs (TLR4/MD-2, TLR1, TLR2, and TLR6) and intracellular TLRs (TLR3, TLR7, TLR8, and TLR9). Cell surface TLRs sense microbial membranes such as lipopolysaccharide or lipopeptides. Recognition by TLRs is the frontline where pathogens and a host try to take the control of immune responses. Bacteria can modulate the structure of a TLR ligand lipid A to subvert host responses. Cell surface TLRs also sense endogenous ligands which are released in tissue damages as danger signals and induce inflammation in infectious and non-infectious condition. The availability of endogenous ligands and the amount of cell surface TLRs are both tightly limited to keep TLR responses sufficient for containment of pathogens without detrimental responses to the host. PMID- 17275325 TI - Isolation, activity and immunological characterisation of a secreted aspartic protease, CtsD, from Aspergillus fumigatus. AB - Aspergillus fumigatus is an opportunistic fungal pathogen that infects immunocompromised patients. A putative aspartic protease gene (ctsD; 1425 bp; intron-free) was identified and cloned. CtsD is evolutionarily distinct from all previously identified A. fumigatus aspartic proteases. Recombinant CtsD was expressed in inclusion bodies in Escherichia coli (0.2mg/g cells) and subjected to extensive proteolysis in the baculovirus expression system. Activation studies performed on purified, refolded, recombinant CtsD resulted in protease activation with a pH(opt)4.0 and specific activity=10 U/mg. Pepstatin A also inhibited recombinant CtsD activity by up to 72% thereby confirming classification as an aspartic protease. Native CtsD was also immunologically identified in culture supernatants and purified from fungal cultures using pepstatin-agarose affinity chromatography (7.8 microg CtsD/g mycelia). In A. fumigatus, semi-quantitative RT PCR analysis revealed expression of ctsD in minimal and proteinaceous media only. Expression of ctsD was absent under nutrient-rich conditions. Expression of ctsD was also detected, in vivo, in the Galleria mellonella virulence model following A. fumigatus infection. PMID- 17275327 TI - Purification and characterization of recombinant ligand-binding domains from the ecdysone receptors of four pest insects. AB - Cloned EcR and USP cDNAs encoding the ecdysone receptors of four insect pests (Lucilia cuprina, Myzus persicae, Bemisia tabaci, Helicoverpa armigera) were manipulated to allow the co-expression of their ligand binding domains (LBDs) in insect cells using a baculovirus vector. Recombinant DE/F segment pairs (and additionally, for H. armigera, an E/F segment pair) from the EcR and USP proteins associated spontaneously with high affinity to form heterodimers that avidly bound an ecdysteroid ligand. This shows that neither ligand nor D-regions are essential for the formation of tightly associated and functional LBD heterodimers. Expression levels ranged up to 16.6mg of functional apo-LBD (i.e., unliganded LBD) heterodimer per liter of recombinant insect cell culture. Each recombinant heterodimer was affinity-purified via an oligo-histidine tag at the N terminus of the EcR subunit, and could be purified further by ion exchange and/or gel filtration chromatography. The apo-LBD heterodimers appeared to be more easily inactivated than their ligand-containing counterparts: after purification, populations of the former were <40% active, whereas for the latter >70% could be obtained as the ligand-LBD heterodimer complex. Interestingly, we found that the amount of ligand bound by recombinant LBD heterodimer preparations could be enhanced by the non-denaturing detergent CHAPS (3-[(3-cholamidopropyl)dimethyl ammonio]-1-propanesulfonate). Purity, integrity, size and charge data are reported for the recombinant proteins under native and denaturing conditions. Certain intra- and intermolecular disulfide bonds were observed to form in the absence of reducing agents, and thiol-specific alkylation was shown to suppress this phenomenon but to introduce microheterogeneity. PMID- 17275326 TI - Expression of membrane proteins from Mycobacterium tuberculosis in Escherichia coli as fusions with maltose binding protein. AB - Sixteen of 22 low molecular weight integral membrane proteins from Mycobacterium tuberculosis with previously poor or undetectable levels of expression were expressed in Escherichia coli as fusions with both the maltose binding protein (MBP) and a His(8)-tag. Sixty-eight percent of targeted proteins were expressed in high yield (>30 mg/L) in soluble and/or inclusion body form. Thrombin cleavage of the MBP fusion protein was successful for 10 of 13 proteins expressed as soluble proteins and for three proteins expressed only as inclusion bodies. The use of autoinduction growth media increased yields over Luria-Bertani (LB) growth media in 75% of the expressed proteins. Expressing integral membrane proteins with yields suitable for structural studies from a set of previously low and non expressing proteins proved highly successful upon attachment of the maltose binding protein as a fusion tag. PMID- 17275328 TI - Purification of a non-tagged recombinant BCG heat shock protein 65-Her2 peptide fusion protein from Escherichia coli. AB - Bacille Calmette-Guerin (BCG)-derived heat shock protein 65 (HSP65) has been demonstrated capable of assisting a fused peptide to generate the peptide specific cellular immunity. Various HSP65 fusion proteins have been developed as therapeutic cancer vaccines. Purifying a recombinant HSP65 fusion protein with no purification tags for human use is routinely a challenge. Here, we report a scheme for purifying a non-tagged recombinant HSP65-Her2 peptide fusion protein (HSP65-Her2) from Escherichia coli. The HSP65-Her2 is being developed as an immunotherapeutic for the treatment of Her2-positive tumors. After fermentation in a 10-L fermentor, the HSP65-Her2 expressing E. coli were harvested and lysed by sonication. The recombinant HSP65-Her2 was then purified with four successive steps including Butyl-Sepharose FF, DEAE-Sepharose FF, 1% Triton X-114 phase separation and Sephadex G-25. Results showed that HSP65-Her2 was purified up to 97% purity and was able to generate Her2-specific cytotoxic T lymphocytes (CTLs), suggesting that the scheme is efficient for purifying the non-tagged HSP65-Her2 fusion protein with biological activity. PMID- 17275329 TI - Expression, purification and characterization of a photoprotein, clytin, from Clytia gregarium. AB - A novel histidine-tagged secretion vector in Escherichia coli was constructed and large amounts of highly pure clytin, a calcium-binding photoprotein, was prepared. The histidine-tagged apoclytin expressed into the periplasmic space in E. coli was purified by nickel chelate affinity chromatography. Recombinant clytin was regenerated from apoclytin by incubation with coelenterazine in the presence of dithiothreitol and then purified by anion-exchange chromatography and hydrophobic chromatography. The yield of recombinant clytin was 20mg from 2L of cultured cells with purity greater than 95%. Luminescence properties of recombinant clytin were identical to that of native clytin (phialidin). The Ca(2+) sensitivity of recombinant clytin is lower than that of aequorin and clytin is suited for measuring higher concentration of Ca(2+). Semi-synthetic clytins were also prepared with coelenterazine analogues, and the initial intensity, luminescence capacity and half decay time were characterized. PMID- 17275330 TI - Remedial strategies in structural proteomics: expression, purification, and crystallization of the Vav1/Rac1 complex. AB - The signal transduction pathway involving the Vav1 guanine nucleotide exchange factor (GEF) and the Rac1 GTPase plays several key roles in the immune response mediated by the T cell receptor. Vav1 is also a unique member of the GEF family in that it contains a cysteine-rich domain (CRD) that is critical for Rac1 binding and maximal guanine nucleotide exchange activity, and thus may provide a unique protein-protein interface compared to other GEF/GTPase pairs. Here, we have applied a number of remedial structural proteomics strategies, such as construct and expression optimization, surface mutagenesis, limited proteolysis, and protein formulation to successfully express, purify, and crystallize the Vav1 DH-PH-CRD/Rac1 complex in an active conformation. We have also systematically characterized various Vav1 domains in a GEF assay and Rac1 in vitro binding experiments. In the context of Vav1-DH-PH-CRD, the zinc finger motif of the CRD is required for the expression of stable Vav1, as well as for activity in both a GEF assay and in vitro formation of a Vav1/Rac1 complex suitable for biophysical and structural characterization. Our data also indicate that the isolated CRD maintains a low level of specific binding to Rac1, appears to be folded based on 1D NMR analysis and coordinates two zinc ions based on ICP-MS analysis. The protein reagents generated here are essential tools for the determination of a three dimensional Vav1/Rac1 complex crystal structure and possibly for the identification of inhibitors of the Vav1/Rac1 protein-protein interaction with potential to inhibit lymphocyte activation. PMID- 17275332 TI - Cajal body number and nucleolar size correlate with the cell body mass in human sensory ganglia neurons. AB - This paper studies the cell size-dependent organization of the nucleolus and Cajal bodies (CBs) in dissociated human dorsal root ganglia (DRG) neurons from autopsy tissue samples of patients without neurological disease. The quantitative analysis of nucleoli with an anti-fibrillarin antibody showed that all neurons have only one nucleolus. However, the nucleolar volume and the number of fibrillar centers per nucleolus significantly increase as a function of cell body size. Immunostaining for coilin demonstrated the presence of numerous CBs in DRG neurons (up to 20 in large size neurons). The number of CBs per neuron correlated positively with the cell body volume. Light and electron microscopy immunocytochemical analysis revealed the concentration of coilin, snRNPs, SMN and fibrillarin in CBs of DRG neurons. CBs were frequently associated with the nucleolus, active chromatin domains and PML bodies, but not with telomeres. Our results support the view that the nucleolar volume and number of both fibrillar centers and CBs depend on the cell body mass, a parameter closely related to transcriptional and synaptic activity in mammalian neurons. Moreover, the unusual large number of CBs could facilitate the transfer of RNA processing components from CBs to nucleolar and nucleoplasmic sites of RNA processing. PMID- 17275333 TI - Non-uniform electromyographic activity during fatigue and recovery of the vastus medialis and lateralis muscles. AB - The aim of the study was to investigate EMG signal features during fatigue and recovery at three locations of the vastus medialis and lateralis muscles. Surface EMG signals were detected from 10 healthy male subjects with six 8-electrode arrays located at 10%, 20%, and 30% of the distance from the medial (for vastus medialis) and lateral (vastus lateralis) border of the patella to the anterior superior spine of the pelvic. Subjects performed contractions at 40% and 80% of the maximal force (MVC) until failure to maintain the target force, followed by 20 2-s contractions at the same force levels every minute for 20 min (recovery). Average rectified value, mean power spectral frequency, and muscle fiber conduction velocity were estimated from the EMG signals in 10 epochs from the beginning of the contraction to task failure (time to task failure, mean+/-SD, 70.7+/-25.8s for 40% MVC; 27.4+/-16.8s for 80% MVC) and from the 20 2s time intervals during recovery. During the fatiguing contraction, the trend over time of EMG average rectified value depended on location for both muscles (P<0.05). After 20-min recovery, mean frequency and conduction velocity of both muscles were larger than in the beginning of the fatigue task (P<0.05) (supernormal values). Moreover, the trend over time of mean frequency during recovery was affected by location and conduction velocity values depended on location for both muscles (P<0.05). The results indicate spatial dependency of EMG variables during fatigue and recovery and thus the necessity of EMG spatial sampling for global muscle assessment. PMID- 17275331 TI - Crystal structure of the multidrug efflux transporter AcrB at 3.1A resolution reveals the N-terminal region with conserved amino acids. AB - Crystal structures of the bacterial multidrug transporter AcrB in R32 and C2 space groups showing both symmetric and asymmetric trimeric assemblies, respectively, supplemented with biochemical investigations, have provided most of the structural basis for a molecular level understanding of the protein structure and mechanisms for substrate uptake and translocation carried out by this 114-kDa inner membrane protein. They suggest that AcrB captures ligands primarily from the periplasm. Substrates can also enter the inner cavity of the transporter from the cytoplasm, but the exact mechanism of this remains undefined. Analysis of the amino acid sequences of AcrB and its homologs revealed the presence of conserved residues at the N-terminus including two phenylalanines which may be exposed to the cytoplasm. Any potential role that these conserved residues may play in function has not been addressed by existing biochemical or structural studies. Since phenylalanine residues elsewhere in the protein have been implicated in ligand binding, we explored the structure of this N-terminal region to investigate structural determinants near the cytoplasmic opening that may mediate drug uptake. Our structure of AcrB in R32 space group reveals an N-terminus loop, reducing the diameter of the central opening to approximately 15 A as opposed to the previously reported value of approximately 30 A for crystal structures in this space group with disordered N-terminus. Recent structures of the AcrB in C2 space group have revealed a helical conformation of this N-terminus but have not discussed its possible implications. We present the crystal structure of AcrB that reveals the structure of the N-terminus containing the conserved residues. We hope that the structural information provides a structural basis for others to design further biochemical investigation of the role of this portion of AcrB in mediating cytoplasmic ligand discrimination and uptake. PMID- 17275334 TI - The association between scalp hair-whorl direction, handedness and hemispheric language dominance: is there a common genetic basis of lateralization? AB - The hemispheres of the human brain are functionally asymmetric. The left hemisphere tends to be dominant for language and superior in the control of manual dexterity. The mechanisms underlying these asymmetries are not known. Genetic as well as environmental factors are discussed. Recently, atypical anticlockwise hair-whorl direction has been related to an increased probability for non-right-handedness and atypical hemispheric language dominance. These findings are fascinating and important since hair-whorl direction is a structural marker of lateralization and could provide a readily observable anatomical clue to functional brain lateralization. Based on data on handedness and hair-whorl direction, Amar Klar proposed a genetic model ("random-recessive model") in that a single gene with two alleles controls both handedness and hair-whorl orientation (Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 165, 269-276). The present study was designed to further investigate the relationship between scalp hair whorl direction with handedness and hemispheric language dominance. 1212 subjects were investigated for scalp hair-whorl direction and handedness. Additionally, we determined hemispheric language dominance (as assessed by a word generation task) in a subgroup of 212 subjects using functional transcranial Doppler sonography (fTCD). As for the single attributes - hair-whorl direction, handedness, and language dominance - we reproduced previously published results. However, we found no association between hair-whorl direction and either language dominance or handedness. These results strongly argue against a common genetic basis of handedness or language lateralization with scalp hair-whorl direction. Inspection of hair patterns will not help us to determine language dominance. PMID- 17275335 TI - Ictal localization by source analysis of infraslow activity in DC-coupled scalp EEG recordings. AB - New bedside long-term DC-coupled EEG techniques have demonstrated that infraslow (<0.5 Hz) activity lateralizes temporal lobe seizures (Vanhatalo, S., Holmes, M.D., Tallgren, P., Voipio, J., Kaila, K., Miller, J.W., 2003a. Very slow EEG responses indicate the laterality of temporal lobe seizures: a DC-EEG study. Neurology 60, 1098-1104). However, even high amplitude infraslow activity is difficult to localize by simple visual inspection if there is overlying faster EEG activity or slow artifact. In this study, we address this with improved DC coupled EEG recording and analysis techniques and also extend observation to both temporal and extratemporal seizures. Recordings were performed during presurgical evaluation of medically intractable epilepsy, with 20 seizures in 11 patients analyzed. A commercial DC-coupled recording device was used, with sintered Ag/AgCl electrodes in a standard 10-10 system array, with additional anterior temporal and subtemporal electrodes. Seizures were localized with a software package by means of source montage analysis. Infraslow signals occurred with all seizures, often with amplitude orders of magnitude higher than conventional frequencies (0.5 to 70 Hz). The most reliable method to localize these signals and distinguish them from artifacts used a source montage after low-pass filtering below 0.5 Hz. Five of the eight patients who received epilepsy surgery had follow-up documenting significant seizure reduction, and infraslow signal analysis correctly localized the region of seizure onset in all five, while conventional noninvasive EEG recording and analysis localized only three of the five. Several seizures were also analyzed using principle component analysis source localization methods, with the results less consistently localizing than source montage analysis. DC-coupled EEG recordings give clinically useful information to noninvasively localize the seizure focus. The value of this method is increased by source analysis tools that reveal localized changes more clearly than direct visual inspection. PMID- 17275336 TI - Neural correlates of two imagined egocentric transformations. AB - Two egocentric spatial transformation tasks, hand and perspective rotation, were compared using the same visual stimulus within both block and event-related functional magnetic resonance imaging (fMRI) paradigms. Both involved body relative judgments but were predicted to vary in the recruitment of the body schema and a motor execution system. The Hand task required the imagined rotation of one's own hand to make a left-right handedness decision. In contrast, the Viewer task required a perspective transformation and updating of the parts of a hand as an object. Previous behavioral and neuroimaging work suggested that hand rotations would rely on dynamic and biomechanical processing of body-part relations recruiting a motor processing system, whereas perspective transformations and the updating of object-self relations would be supported by primarily visual-spatial mechanisms. There was a common neural substrate found for both tasks including the lateral occipital areas, inferior and superior parietal cortex, and the cerebellum. Direct comparisons between the two tasks revealed greater activation in the Hand task in left superior and inferior parietal and premotor cortex and cerebellum, whereas the Viewer task showed greater activation only in the right lingual and fusiform gyri. Degree of rotation also modulated activity in the Hand task in bilateral superior parietal and premotor cortex, but not in the Viewer task. Implications of these regions for the role of dynamic body schema and motor processing in egocentric transformations are discussed. PMID- 17275338 TI - Impact of ventricular enlargement on the measurement of metabolic activity in spatially normalized PET. AB - In pathologic brains with morphological alterations, the process of spatial normalization, as performed by SPM methods, may introduce a confounding effect in the measurement of metabolic activity data. To investigate the effect of the spatial normalization of PET images, we analyzed MRI and PET studies of 20 schizophrenic patients and 18 controls. Using a Talairach-based segmentation procedure and manual segmentation, we measured regional metabolic activity in the untransformed brains and after their spatial normalization. The effect of spatial normalization seems minimal for large ROIs like the main brain lobes, even in brains showing pronounced morphological abnormalities. However, the caudate nucleus shows a considerable change in metabolic activity values after normalization. This normalization effect is much larger in patients than in controls, and leads to artifactual differences between them. We obtained incorrect results (SPM analysis) regarding functional differences between patients and controls in the caudate due to this bias introduced by the spatial normalization. There was a significant correlation between the size of the lateral ventricles and the underestimation of metabolic activity of the caudate. Normalization bias seems to arise from a misalignment of the caudate in the normalized space, pixel overlap between the normalized caudate, and the caudate of the template being on average lower than 50% in both groups. Spatial normalization of the PET images of pathologic brains may introduce a potential source of error that should be taken into account in the analysis of functional data, in particular, in the study of small brain nuclei like the caudate. PMID- 17275337 TI - Abnormal brain connectivity in first-episode psychosis: a diffusion MRI tractography study of the corpus callosum. AB - A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the clinical manifestations of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail and we present here a study of patients with first episode psychosis using this technique. We selected the corpus callosum for this study because there is evidence that it is abnormal in schizophrenia. In addition, the topographical organization of its fibers makes it possible to relate focal abnormalities to specific cortical regions. Eighteen patients with first-episode psychosis and 21 healthy subjects took part in the study. A probabilistic tractography algorithm (PICo) was used to study fractional anisotropy (FA). Seed regions were placed in the genu and splenium to track fiber tracts traversing these regions, and a multi-threshold approach to study the probability of connection was used. Multiple linear regressions were used to explore group differences. FA, a measure of tract coherence, was reduced in tracts crossing the genu, and to a lesser degree the splenium, in patients compared with controls. FA was also lower in the genu in females across both groups, but there was no gender-by-group interaction. The FA reduction in patients may be due to aberrant myelination or axonal abnormalities, but the similar tract volumes in the two groups suggest that severe axonal loss is unlikely at this stage of the illness. PMID- 17275339 TI - Precise mapping of early visual responses in space and time. AB - We used magnetoencephalography (MEG) to record brain activity while subjects passively viewed stimuli presented at eight different locations in the parafoveal and peripheral visual fields (VF). For each subject, the experiment was repeated on 3 different days. The generators of the early MEG signal components were localized using tomographic source analysis together with statistical parametric mapping. We identified activations throughout visual cortex in the first 100 ms of stimulus onset. The earliest stimulus-evoked responses were registered in V1. Then, activity with largely overlapping latencies spread rapidly to V2, V3 and throughout the whole visual system. Unambiguous and focal activations with precise onset, peak latencies, and peak amplitudes for each subject and day were identified in V1, in one ventral and three dorsal stream areas. Activations in all areas were consistent in location and timing across subjects and for each subject they were highly reproducible across 3 experimental days. Localization precision was typically within 2 mm in all areas. Retinotopic organizations of the identified areas were in good agreement with other neuroimaging and animal studies. The localization accuracy, as evidenced by computer simulations, was in line with our earlier fMRI/MEG study. On average, it was around 2 mm. Here we report, with very high reproducibility, the dynamics of early visual area activations and their dependence on the stimulated location of the VF. These results show for the first time in humans, significantly shorter onset latencies in V1 for peripheral than parafoveal VF stimulations. PMID- 17275341 TI - Parsing a sequence of brain activations at psychological times using fMRI. AB - Identifying the sequence of computations which constitute a cognitive task is a fundamental problem in neuroscience. Here we show, using functional magnetic resonance imaging (fMRI), that we can parse, at the time scale of about 100 ms, the different stages of brain activations which compose a complex sequential task. To identify timing information from the slow blood oxygen level-dependent (BOLD) signal response, we use a simple analytic method, based on periodic stimulation and an analysis of covariation of the spectral parameters (phase and power spectrum at the stimulation frequency) with the different experimental conditions. We implement this strategy in a sequential task, where the onset and duration of different stages are under experimental control. We are able to detect changes in onset latency and in the duration of the response, in an invariant fashion across different brain regions, and reconstruct the stream of activations consistent with five distinct stages of processing of the task. Sensory and motor clusters activate in the expected order and for the expected duration. The timing of sensory activations is more precise than the timing of motor activation. We also parse in time the reading-verbal network: visual extrastriate and phonological access regions (supramarginal gyrus) activate at the time of word presentation, while the inferior frontal gyrus, the anterior cingulate and the supplementary motor area are activated during the rehearsal period. PMID- 17275342 TI - Evolutionary differentiation in the Neotropical montane region: molecular phylogenetics and phylogeography of Buarremon brush-finches (Aves, Emberizidae). AB - Studies on Neotropical phylogeography have largely focused on lowland organisms. Because lowland and highland biotas have different histories and are likely affected by different processes influencing population differentiation, understanding Neotropical diversification requires detailed studies on montane taxa. We present the most comprehensive analysis of population differentiation conducted so far on a widespread group of Neotropical montane organisms, focusing on the evolutionary relationships and phylogeography of Buarremon brush-finches (Aves: Emberizidae) in montane areas from Mexico through Argentina. Sequences of mitochondrial and nuclear genes demonstrate that Buarremon is not monophyletic with respect to Arremon and Lysurus. Genetic structure revealed by mtDNA is strong in both B. brunneinucha and B. torquatus. Gene genealogies and nucleotide diversity indicate that B. brunneinucha originated in Mexico and later expanded to South America, where it followed one colonization route through the east, and one through the west of the continent. Differentiation among populations of B. torquatus was substantial, reaching 8% uncorrected sequence divergence within South America. Relationships among major lineages of B. torquatus were not fully resolved owing to rapid differentiation, but the occurrence of closely related taxa in distant locations suggests a complex history of diversification. Some Colombian populations of B. brunneinucha have affinities with populations from Venezuela and the East Andean slope of Ecuador and Peru, and others with those from the Pacific slope of Ecuador. Moreover, five divergent lineages of B. torquatus occur within Colombia, highlighting the importance of dense sampling in northwest South America for studies on diversification of widespread Neotropical lineages. PMID- 17275343 TI - Molecular phylogenetic dating supports an ancient endemic speciation model in Australia's biodiversity hotspot. AB - Southwestern Australia (SWA) is a region of temperate Mediterranean climate isolated by desert from the rest of Australia. Since the Jurassic it has been a geologically stable area that resisted Cenozoic glaciations and today represents an ancient landscape characterized by subdued topography and nutrient-poor soils. Despite these ecological conditions, SWA contains an incredibly rich flora and fauna that includes a great diversity of endemic species and it recently has been identified as a biodiversity hotspot of international significance. Since the early recognition of the high floral diversity in SWA and subsequent recognition of high faunal diversity, much discussion has focused on the origins of this rich endemic biota. Two alternative models have been proposed--the Multiple Invasion Hypothesis and the Endemic Speciation Hypothesis. Multiple tests of these models have variously supported either one, but many of the tests have been poor. Here we use a phylogeny for the myobatrachid frog genus Heleioporus to distinguish between these hypotheses. Heleioporus comprises six species: five endemic to southwestern Australia with one from eastern Australia. A molecular phylogeny using two mitochondrial genes (ND2 and 12S rDNA) and one nuclear gene (rag1) was used to test alternative theories about the biogeography and the origin of diversity in this genus. Using a relaxed molecular clock, the divergence between the eastern and western species was dated at 25.60 M years, which is considerably older than previously suggested. Our phylogeny of Heleioporus is inconsistent with previous biogeographic hypotheses involving repeated invasions from the east to the west and some previous in situ models and instead strongly supports an ancient endemic speciation model. While the split between east and west appears to be contemporaneous with similar splits in Geocrinia (Anura) and Banksia (Proteaceae) it is much older than splits in a range of other taxa including other anurans. PMID- 17275340 TI - Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus. AB - Chronic stress in non-human animals decreases the volume of the hippocampus, a brain region that supports learning and memory and that regulates neuroendocrine activity. In humans with stress-related psychiatric syndromes characterized by impaired learning and memory and dysregulated neuroendocrine activity, surrogate and retrospective indicators of chronic stress are also associated with decreased hippocampal volume. However, it is unknown whether chronic stress is associated with decreased hippocampal volume in those without a clinical syndrome. We tested whether reports of life stress obtained prospectively over an approximate 20-year period predicted later hippocampal grey matter volume in 48 healthy postmenopausal women. Women completed the Perceived Stress Scale repeatedly from 1985 to 2004; in 2005 and 2006, their hippocampal grey matter volume was quantified by voxel-based morphometry. Higher Perceived Stress Scale scores from 1985 to 2004 - an indicator of more chronic life stress - predicted decreased grey matter volume in the right orbitofrontal cortex and right hippocampus. These relationships persisted after accounting for age, total grey matter volume, time since menopause, use of hormone therapy, subclinical depressive symptoms, and other potentially confounding behavioral and age-related cerebrovascular risk factors. The relationship between chronic life stress and regional grey matter volume - particularly in the hippocampus and orbitofrontal cortex - appears to span a continuum that extends to otherwise healthy individuals. Consistent with animal and human clinical evidence, we speculate that chronic-stress-related variations in brain morphology are reciprocally and functionally related to adaptive and maladaptive changes in cognition, neuroendocrine activity, and psychiatric vulnerability. PMID- 17275344 TI - DNA sequences identify numerous cryptic species of the vertebrate: a lesson from the gobioid fish Schindleria. AB - Schindleria (Gobioidei, Schindleriidae), believed to include one of the smallest and youngest reproducing vertebrates, is broadly distributed in the Indo-Pacific Oceans, inhabiting coral reef lagoons. They are all characterized by a reduced larval-like form, such as a slender translucent and scaleless body. The three nominal species recognized in the genus to date have been distinguished by only combination of dorsal and anal fin-ray counts, and the existence of some undescribed species has been suggested in Schindleria; thus a total picture of species composition of the genus is poorly known. Towards the disclosure of diversity of Schindleria, a molecular phylogenetic analysis using partial mitochondrial 16S rRNA sequences was conducted for specimens from the Ryukyu and Ogasawara Islands, Japan. This analysis showed clearly that as many as 21 genetically distinguishable species occurred within the geographical areas. The degree of species crypticness of "S. praematura" [15.0=15 (new cryptic species + known species)/1 (known species)] is higher than the values of well-known animal examples, such as the pan-mesopelagic bristlemouth fish Cyclothone alba (5.0) and the South American skipper butterfly Astraptes fulgerator (10.0). This discovery of many cryptic species in Schindleria suggests that the use of DNA sequences is necessary for species identification of such morphologically conserved taxa. Because molecular analyses should increase the number of hitherto unnamed and pseudonymous species, especially in tropical areas, it is proposed that DNA-based designation is necessary for such taxa in order to compile the full "species lists", although there is presently no consensus for the inclusion of DNA sequencing data in the formal descriptions of new species. PMID- 17275346 TI - Y chromosome genetic variation in the Italian peninsula is clinal and supports an admixture model for the Mesolithic-Neolithic encounter. AB - The Italian peninsula, given its geographical location in the middle of the Mediterranean basin, was involved in the process of the peopling of Europe since the very beginning, with first settlements dating to the Upper Paleolithic. Later on, the Neolithic revolution left clear evidence in the archeological record, with findings going back to 7000 B.C. We have investigated the demographic consequences of the agriculture revolution in this area by genotyping Y chromosome markers for almost 700 individuals from 12 different regions. Data analysis showed a non-random distribution of the observed genetic variation, with more than 70% of the Y chromosome diversity distributed along a North-South axis. While the Greek colonisation during classical time appears to have left no significant contribution, the results support a male demic diffusion model, even if population replacement was not complete and the degree of Neolithic admixture with Mesolithic inhabitants was different in different areas of Italy. PMID- 17275347 TI - Phylogenetic relationships among Nearctic shrews of the genus Sorex (Insectivora, Soricidae) inferred from combined cytochrome b and inter-SINE fingerprint data using Bayesian analysis. AB - The field of molecular systematics has relied heavily on mitochondrial DNA (mtDNA) analysis since its inception. Despite the obvious utility of mtDNA, such data inevitably only presents a limited (i.e., single genome) perspective on species evolution. A combination of mitochondrial and nuclear markers is essential for reconstructing more robust phylogenetic trees. To evaluate the utility of one category of nuclear marker (short interspersed elements or SINEs) for resolving phylogenetic relationships, we constructed an inter-SINE fingerprint for nine putative species of the genus Sorex. In addition, we analyzed 1011 nucleotides of the cytochrome b gene. Traditional neighbor-joining and maximum parsimony analyses were applied to the individual cytochrome b and inter-SINE fingerprint data sets, along with Bayesian analysis to the combined data sets. We found inter-SINE fingerprinting to be an effective species level marker; however, we were unable to reconstruct deeper branching patterns within the Sorex genus using these data. The combined data analyzed under a Bayesian analysis showed higher levels of structuring within the Otisorex subgenus, most notably recognizing a monophyletic group consisting of sister-taxa S. palustris and S. monticolus, S. cinereus and S. haydeni, and S. hoyi. An additional noteworthy result was the detection of an historic mitochondrial introgression event between S. monticolus and S. palustris. When combining disparate data sets, we emphasize researcher diligence as certain types of data and processes may overly influence the analysis. However, there is considerable phylogenetic potential stemming from inter-SINE fingerprinting. PMID- 17275345 TI - Systematics, biogeography, and evolution of the Neotropical peacock basses Cichla (Perciformes: Cichlidae). AB - To investigate forces influencing diversification in Neotropical fishes, the phylogenetic relationships among species and populations of the cichlid genus Cichla were examined. Mitochondrial DNA was sequenced for 454 individuals of the 5 nominal Cichla species and several putative undescribed species. Phylogenetic analyses support the distinction of two major clades of Cichla. Clade A includes C. temensis and two undescribed species from the lower Amazonas and Xingu Rivers. Clade B includes C. orinocensis, C. monoculus, C. ocellaris. C, intermedia, and an undescribed species from the upper Madeira River. Species boundaries were relatively well-circumscribed for clade B, while incomplete lineage sorting was inferred for clade A. Three probable instances of introgression were observed, including a regional population of C. orinocensis from the Negro River that shows a history of introgression. Biogeographic patterns from Cichla are partially congruent with those seen in several other Neotropical fish clades, and the diversification of Cichla species is inferred to result from both vicariance and sympatric divergence. PMID- 17275348 TI - Biogeographical and phylogenetic origins of African fig species (Ficus section Galoglychia). AB - Ficus section Galoglychia (subgenus Urostigma; Moraceae) includes 72 species restricted to the African floristic region (a few extending to the Arabian Peninsula and Socotra). We present the first molecular phylogenetic analysis of the section including 56 ingroup (representing 44 species) and three outgroup taxa, to investigate its monophyly, classification and evolution. We used sequence data from the nuclear ribosomal internal and external transcribed spacers (ITS and ETS). Our results suggest that section Galoglychia is paraphyletic to the neotropical section Americana, although this is not supported by bootstrap analysis and only weakly supported by Bayesian posterior probabilities. Maximum parsimony analysis conflict with maximum likelihood and Bayesian analyses with respect to the closest relatives of section Americana in Africa. The subsections of section Galoglychia proposed by Berg [Berg, C.C., 1986. Subdivision of Ficus subg. Urostigma sect. Galoglychia (Moraceae). Proc. Kon. Ned. Akad. Wetensch., Ser. C, 89, 121-127] are generally supported. We find two major clades of section Galoglychia within Africa possibly corresponding to two main centres of diversity. One clade comprises members of subsections Platyphyllae and Chlamydodorae, which are more concentrated in Eastern Africa, and extend to Madagascar and neighbouring archipelagos (Comores, Mascarenes, Aldabra Islands and Seychelles). The other main clade includes members of subsections Caulocarpae, Cyathistipulae, Crassicostae and Galoglychia, which are concentrated in West and Central Africa. PMID- 17275349 TI - Phylogeny and biogeography of paradoxical frogs (Anura, Hylidae, Pseudae) inferred from 12S and 16S mitochondrial DNA. AB - We used mitochondrial DNA sequences of 12S and 16S ribosomal RNA genes to reconstruct phylogenetic relationships of the nine species of South American aquatic hylids known as paradoxical frogs. Pseudis minuta and P. cardosoi form the sister-group to a clade comprising Lysapsus and the remaining Pseudis. We suggest the resurrection of Podonectes, including P. minutus and P. cardosoi, to avoid the nonmonophyly of Pseudis. Some doubt is cast on the species status of P. cardosoi. Lysapsus limellum, P. bolbodactyla, and P. paradoxa each may comprise more than one species, but lack of comprehensive geographic and morphological appraisals precludes taxonomic changes. Biogeographic implications of the phylogeny are discussed. The correlation between hydrographic basins and Pseudis species is not fully supported, and a recent contact between Amazon populations in eastern Bolivia and western Brazil (Rondonia) and Parana basin populations in the Pantanal is suggested. A dispersal-vicariance analysis showed that major diversification of Pseudis and Lysapsus species occurred in the Brazilian Shield, and that the presence of P. paradoxa and L. limellum in the Amazon and Parana basins is due to recent dispersals. Evidence suggests a vicariant event, most likely caused by Miocene marine introgressions, as the cause for the restricted distribution of L. laevis in the Guiana Shield. PMID- 17275350 TI - Re-assessed molecular phylogeny and evolutionary scenario within genets (Carnivora, Viverridae, Genettinae). PMID- 17275351 TI - The effect of model choice on phylogenetic inference using mitochondrial sequence data: lessons from the scorpions. AB - Chelicerates are a diverse group of arthropods, with around 65,000 described species occupying a wide range of habitats. Many phylogenies describing the relationships between the various chelicerate orders have been proposed. While some relationships are widely accepted, others remain contentious. To increase the taxonomic sampling of species available for phylogenetic study based on mitochondrial genomes we produced the nearly complete sequence of the mitochondrial genome of the scorpion Mesobuthus gibbosus. Mitochondrial gene order in M. gibbosus largely mirrors that in Limulus polyphemus but tRNA secondary structures are truncated. A recent analysis argued that independent reversal of mitochondrial genome strand-bias in several groups of arthropods, including spiders and scorpions, could compromise phylogenetic reconstruction and proposed an evolutionary model that excludes mutational events caused by strand bias (Neutral Transitions Excluded, NTE). An arthropod dataset of six mitochondrial genes, when analyzed under NTE, yields strong support for scorpions as sister taxon to the rest of Chelicerata. We investigated the robustness of this result by exploring the effect of adding additional chelicerate genes and taxa and comparing the phylogenies obtained under different models. We find evidence that (1) placement of scorpions arising at the base of the Chelicerata is an artifact of model mis-specification and scorpions are strongly supported as basal arachnids and (2) an expanded chelicerate dataset finds support for several proposed interordinal relationships (ticks plus mites [Acari] and spiders plus whip spiders plus whip scorpions [Araneae+Pedipalpi]). Mitochondrial sequence data are subject to systematic bias that is positively misleading for evolutionary inference and thus extreme methodological care must be taken when using them to infer phylogenies. PMID- 17275352 TI - Biomechanical comparison of different pin configurations during percutaneous pinning for the treatment of proximal humeral fractures. AB - We investigate the influence on fracture stability of different pin configurations during percutaneous pinning for the treatment of proximal humeral fractures. We performed a matched-paired study of 18 pairs of adult fresh-frozen humeri (36 humeri), which were divided into 4 groups. A 2-part surgical neck fracture model was used in all humeri, and 4 terminal threaded pins (2.5 mm in diameter) were used for fixation. Parallel-type pinning (box type) was carried out in 2 groups, and convergent-type pinning (fan-shaped type) was used in the other 2 groups. For each specimen, both anti-shear ultimate load and anti-torsion ultimate load were measured. There was no statistical difference between the parallel pin construct and convergent construct with regard to anti-shear resistance (P = .73). However, the parallel pin construct had a significant advantage over the convergent construct regarding anti-torsion resistance. The parallel pin construct has better torsional stability when 1 cm is used for the pin-to-pin distance. We suggest that parallel pin fixation should be applied whenever possible. PMID- 17275354 TI - Posterior dislocation of the long head of the biceps tendon. PMID- 17275355 TI - Shoulder arthroplasty in sickle cell patients with humeral head avascular necrosis. AB - The purpose of this study was to evaluate the results of shoulder arthroplasty for the treatment of avascular necrosis in patients with sickle cell disease. Medical records, radiographs, operative reports, and outcome scores of 8 adult patients with sickle cell disease were evaluated. The mean follow-up was 51 months (range, 2-10 years). Seven patients had a hemiarthroplasty, and one had a total shoulder arthroplasty. One patient had an intraoperative rotator cuff tear. Two had sickle cell crises in the immediate postoperative period. In one patient, stiffness developed that required arthroscopic capsular release 22 months after her arthroplasty. Another patient with a hemiarthroplasty underwent revision to a total shoulder arthroplasty 5 years after the index procedure. The mean American Shoulder and Elbow Surgeons score improved by 31.9 points. However, only 2 patients reported improvement in pain as assessed with a visual analog scale. Although shoulder arthroplasty provides improvements in range of motion and function in the majority of patients, pain relief is less predictable. PMID- 17275356 TI - Effects of D-cycloserine on extinction of learned fear to an olfactory cue. AB - D-cycloserine (DCS), a partial NMDA receptor agonist, facilitates extinction of learned fear in rats and has been used to treat anxiety disorders in clinical populations. However, research into the effects of DCS on extinction is still in its infancy, with visual cues being the primary fear-eliciting stimuli under investigation. In both human and animal subjects odors have been found to associate strongly with aversive events. Therefore, this study examined the generality of the effects of DCS on extinction by testing odor cues. Sprague Dawley rats were conditioned and extinguished to an odor using varying parameters, injected with either saline or DCS (15 mg/kg) following extinction, and then tested for a freezing response 24 h later. Experiment 1 demonstrated that after 3 odor-shock pairings, rats did not display short-term extinction and DCS had no effect on long-term extinction. Experiment 2 demonstrated that after 3 odor-noise pairings, rats displayed significant short-term extinction and DCS significantly facilitated long-term extinction. Following 2 odor-shock pairings in Experiment 3, half the rats displayed short-term extinction ("extinguishers") and half did not ("non-extinguishers"). DCS facilitated long-term extinction in the "extinguishers" condition but not in the "non-extinguishers" condition. In Experiment 4, following 2 odor-shock pairings and an extra extinction session, DCS had a significant facilitatory effect on long-term extinction. Thus, extinction of freezing to an odor cue was facilitated by systemic injections of DCS, but only when some amount of within-session extinction occurred prior to injection. PMID- 17275359 TI - Branched grafting for aortoiliac aneurysms. AB - PURPOSE: To evaluate a novel approach to preserve pelvic perfusion during endovascular AAA repair in patients with common iliac aneurysms extending to the iliac bifurcation. MATERIALS AND METHODS: A multicenter prospective analysis of patients undergoing implantation of a branched endograft designed to perfuse the internal iliac artery was conducted. All patients enrolled were considered high risk for open surgical repair and presented with common iliac artery aneurysms greater than 20mm and anatomy amenable to implant the branched device. Preoperative high resolution spiral CT, and follow-up CT studies in addition to abdominal radiographs were obtained at discharge, 1, 6, 12, and 24 months. RESULTS: Between 2003 and 2006, 52 patients (53 internal iliacs) were implanted with an investigational device. Mean common iliac aneurysm maximal diameter was 38 mm. The branch graft was combined with a proximal standard bifurcated component (61%), a fenestrated or a visceral branch component (33%), an aortouni iliac component (2%), and alone in 2 patients (4%, following prior aortobi-iliac repair). Technical success was achieved in 94% of patients. Within the first month, 6 (11%) internal iliac branches occluded. No occlusions were noted after 1 month. The mean follow-up was 14.2 months. Common iliac aneurysm shrinkage was noted in 42% and 81% of patients at 6 and 12 months. There were no rupture, aneurysm related deaths or conversions, but there were 7 deaths during follow-up. CONCLUSIONS: The placement of endovascular prostheses that maintain antegrade perfusion of one or both internal iliac arteries is feasible, and early results provide evidence for optimism with regard to safety and efficacy. PMID- 17275360 TI - Should cardiac troponins be used as a risk stratification tool for patients with chronic critical limb ischaemia? AB - OBJECTIVES: Cardiovascular mortality in patients with chronic critical lower limb ischaemia (CCLI) is high and early risk stratification in these patients may aid clinical management improving outcomes. Cardiac troponin I (cTnI) has prognostic significance in patients with unstable angina. The aim of this study was to evaluate the prognostic significance of cardiac troponins in CCLI patients who had no clinical evidence of unstable coronary heart disease. METHODS: Patients (n=152) admitted with CCLI to a single vascular unit over a two-year period were included prospectively in this study. Patients with clinical evidence of unstable coronary disease were excluded from the study. Patient demographics, clinical history, co-morbidity and risk factors for peripheral vascular disease were documented. Admission cTnI levels were recorded using a threshold, 0.1 ng/ml. The primary endpoint was mortality. RESULTS: Fifty-two patients (34.2%) had an elevated cTnI, whilst 100 (65.8%) had cTnI <0.1 ng/ml. Sixty-two patients died during the follow-up period, 38 with an elevated admission cTnI. Death rate in patients with cTnI >0.1 ng/nl was 73% compared with 24% in those with levels below the threshold (p<0.0001). Patients with elevated cTnI were significantly older than those with normal level (median age 76 years vs 71 years, p<0.001). An elevated cTnI was found to independently predict disease-specific mortality on Cox regression analysis (Hazard Ratio 4.2; 95% Confidence Interval 1.3-12.7). CONCLUSION: In this series of patients with CCLI the measurement of cTnI on admission was a significant independent predictor of survival. cTnI has potential as a prognostic test to stratify patients with a high cardiovascular risk and may enable further optimisation of these high-risk patients. PMID- 17275357 TI - Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages. AB - gp96 is an endoplasmic reticulum chaperone for cell-surface Toll-like receptors (TLRs). Little is known about its roles in chaperoning other TLRs or in the biology of macrophage in vivo. We generated a macrophage-specific gp96-deficient mouse. Despite normal development and activation by interferon-gamma, tumor necrosis factor-alpha, and interleukin-1beta, the mutant macrophages failed to respond to ligands of both cell-surface and intracellular TLRs including TLR2, TLR4, TLR5, TLR7, and TLR9. Furthermore, we found that TLR4 and TLR9 preferentially interacted with a super-glycosylated gp96 species. The categorical loss of TLRs in gp96-deficient macrophages operationally created a conditional and cell-specific TLR null mouse. These mice were resistant to endotoxin shock but were highly susceptible to Listeria monocytogenes. Our results demonstrate that gp96 is the master chaperone for TLRs and that macrophages, but not other myeloid cells, are the dominant source of proinflammatory cytokines during endotoxemia and Listeria infections. PMID- 17275361 TI - The predictive value of haemodynamic assessment in chronic venous leg ulceration. AB - OBJECTIVES: The aim of this study was to assess the value of PPG in predicting healing and recurrence in patients with chronic venous ulceration. METHODS: 500 patients with open or recently healed venous ulceration were treated with either multilayer compression or compression plus superficial venous surgery and followed up in specialist clinics as part of a clinical study. At initial assessment, VRT was measured using PPG with and without a below-knee tourniquet inflated to 80 mmHg to occlude superficial veins. Legs were stratified into groups with VRT <11s, 11-20s and >20s and comparison of healing and recurrence rates between these groups was performed. RESULTS: VRT measurements were not achieved in 117 patients, primarily due to ankle stiffness. Of the remaining 383 patients, VRT without tourniquet did not correlate with ulcer healing (p=0.26, 0.40) or recurrence (p=0.20, 0.79, Log rank test) for legs treated with compression or compression plus surgery respectively. However, VRT readings taken with a below-knee tourniquet were predictive of ulcer healing (p<0.01) and recurrence (p=0.05, Log-rank test). The correlation was greatest for healing in legs treated with compression alone, where 24 week healing rates were 62%, 73% and 92% for legs with VRTs with tourniquet <11s, 11-20s and >20s respectively (p<0.01, Log rank test). For legs treated with surgery, 1 year recurrence rates were 24%, 10% and 3% for groups with VRTs with tourniquet <11s, 11-20s and >20s respectively (p=0.03, Log rank test). CONCLUSIONS: Digital PPG assessment may predict ulcer healing and recurrence, but only by using a below-knee tourniquet. This information could aid the selection of patients with venous ulceration most likely to benefit from superficial venous surgery. PMID- 17275362 TI - Popliteal artery aneurysm with acute ischemia in 229 patients. Outcome after thrombolytic and surgical therapy. AB - OBJECTIVES: The aim of this study was to assess the national management and outcome of popliteal artery aneurysm (PAA). METHODS: In the Swedish National Registry 717 primary operations for PAA on 571 patients were registered prospectively between 1987 and 2002. 235 legs [corrected] presented with acute ischemia. RESULTS: Median age was 70 for men and 75 for women. Immediate surgery was performed in 135 legs, including intraoperative thrombolysis in 32 cases (Immediate Surgery Group, ISG). Pre-operative thrombolysis was performed in 100 legs, followed by acute (90% of the maximum was estimated between 17.6 and 24.9 degrees C and between 18.5 and 36.7 per thousand, respectively. The results suggest that the power model fits well to the observed endurance estimates and the SAI is a good index to quantitatively describe the overall swimming ability of L. vannamei. Furthermore, temperature and salinity can limit the swimming performance of L. vannamei. PMID- 17275373 TI - QSAR method for prediction of protein-peptide binding affinity: application to MHC class I molecule HLA-A*0201. AB - The support vector machine (SVM), which is a novel algorithm from the machine learning community, was used to develop quantitative structure-activity relationship (QSAR) models for predicting the binding affinity of 152 nonapeptides, which can bind to class I MHC HLA-A*201 molecule. Each peptide was represented by a large pool of descriptors including constitutional, topological descriptors and physical-chemical properties. The heuristic method (HM) was then used to search the descriptor space for selecting the proper ones responsible for binding affinity. The four descriptors were obtained to build linear models based on HM and nonlinear models based on SVM method. The best results are found using SVM: root mean-square (RMS) errors for training, test and whole data set were 0.383, 0.385 and 0.384, respectively. This paper allow the prediction of the binding affinity of new, untested peptides and, through the analysis of contribution of each parameter of different residue at specific position of peptidic ligands, to understand nature of the forces governing binding behavior and suggest new ideas for further synthesis of high-affinity peptides. PMID- 17275375 TI - Insect cold tolerance and repair of chill-injury at fluctuating thermal regimes: role of ion homeostasis. AB - Adults of the bug Pyrrhocoris apterus and the beetle Alphitobius diaperinus developed chill-injury slower and survived longer when they were exposed to fluctuating thermal regimes (FTRs, where periods of low temperature were alternated with periods of higher temperature on a daily basis) rather than to constant low temperatures. The extracellular (haemolymph) concentrations of potassium ions increased with significantly higher rates in the insects exposed to constant low temperatures than in those exposed to FTRs. The concentrations of magnesium and sodium ions were maintained relatively constant or decreased slightly in both thermal regimes. The loss of body water and the increase of haemolymph osmolality contributed to, but could not fully explain, the ion concentration changes, which probably resulted also from impairing the function of an active metabolic component (ion pump) at low temperatures. This explanation was supported by observing (in P. apterus) the return toward normal [K+] during the warm "recovery" period of the FTR. Collectively, the paper stresses the importance of considering the temperature fluctuations in the experimental studies on insect cold tolerance and suggests that the positive effect of the FTR on cold tolerance may consist, at least partially, in allowing the primary ion pumping systems to re-establish the ion gradients across cell membranes and epithelia during the recovery periods at a higher temperature. PMID- 17275376 TI - Identification of cDNAs encoding HSP70 and HSP90 in the abalone Haliotis tuberculata: Transcriptional induction in response to thermal stress in hemocyte primary culture. AB - Heat-shock proteins are a multigene family of proteins whose expression is induced by a variety of stress factors. This work reports the cloning and sequencing of HSP70 and HSP90 cDNAs in the gastropod Haliotis tuberculata. The deduced amino acid sequences of both HSP70 and HSP90 from H. tuberculata shared a high degree of homology with their homologues in other species, including typical eukaryotic HSP70 and HSP90 signature sequences. We examined their transcription expression pattern in abalone hemocytes exposed to thermal stress. Real-time PCR analysis indicated that both HSP70 and HSP90 mRNA were expressed in control animals but rapidly increased after heat-shock. PMID- 17275377 TI - Characterization of chicken cystatin binding to rat renal brush-border membranes. AB - Chicken cystatin, a homologue of human cystatin C, like other low-molecular weight proteins is metabolized by renal proximal tubule cells. However, the precise mechanism(s) of this process has not been elucidated yet. To characterize chicken cystatin binding to renal brush-border membranes, the incubation of fluorescein labelled protein with rat cortical homogenate was performed. Saturation-dependent and reversible binding with low affinity (K(d)=3.67-4.07 microM) and high capacity (B(max)=2.32-2.79 nmol/mg) was observed. Bovine albumin was the most potent competitor (K(i)=0.7 microM) among other megalin/cubilin ligands tested. The presence of Ca(+2) ions was necessary to effective cystatin binding by brush-border membranes. Obtained data strongly support the hypothesis that chicken cystatin is a novel ligand for megalin/cubilin receptors tandem on proximal tubular cells. PMID- 17275378 TI - A novel mutation in the human complex I NDUFS7 subunit associated with Leigh syndrome. AB - Defects in NADH:ubiquinone oxidoreductase, the complex I of the mitochondrial respiratory chain represents the most frequent cause of mitochondrial diseases and is associated with a wide clinical spectrum varying from severe lactic acidosis in infants to muscle weakness in adults. Here, we report a patient with Leigh syndrome (LS), born to consanguineous parents, with severe complex I defect and a novel mutation in the NDUFS7 gene subunit. The homozygous mutation at nucleotide (nt) 434 G>A resulted in the modification of the arginine 145 to histidine in a highly conserved region of the protein. Parents were heterozygous carriers for this mutation. The mutation was absent from over than 100 healthy controls from the same ethnic origin. Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us to understand how moleculardefects can lead to complex I deficiency. PMID- 17275380 TI - Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient. AB - Abetalipoproteinemia (ABL) is a rare autosomal recessive metabolic disorder, characterized by the absence of plasma apolipoprotein B-containing lipoproteins and very low levels of plasma triglycerides and cholesterol. ABL is caused by mutations of the MTP gene. We investigated the genetic basis for ABL in a cohort of Israeli families. In Ashkenazi Jewish patients we identified a conserved haplotype and a common MTP mutation, p.G865X, with a carrier frequency of 1:131 in this population. We also report the first case of ABL and additional abnormalities in a Muslim Arab patient, due to a homozygous contiguous gene deletion of approximately 481 kb, including MTP and eight other genes. PMID- 17275379 TI - Ethnic-specific distribution of mutations in 716 patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. AB - Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) occurs worldwide. The most common mutations in the CYP21A2 gene in 716 unrelated patients were analyzed and the mutations were grouped by ethnicity, as defined through self-declaration corroborated by review of pedigrees extending to two or three generations. Prevalent allelic mutations and genotypes were found to vary significantly among ethnic groups, and the predominance of the prevalent mutations and genotypes in several of these populations was significant. There are ethnic-specific mutations in the CYP21A2 gene. A large deletion is prevalent in the Anglo-Saxons; a V281L (1685 G to T) mutation is prevalent in Ashkenazi Jews; an R356W (2109 G to A) mutation is prevalent in the Croatians; an IVS2 AS 13 (A/C to G) mutation is prevalent in the Iranians and Yupik-speaking Eskimos of Western Alaska; and a Q318X (1994 C to T) mutation is prevalent in East Indians. Genotype/phenotype non-correlation was seen when at least one IVS2 AS -13 (A/C to G) mutation in the CYP21A2 gene was present. PMID- 17275381 TI - [Reply of H. Letur to the editorial by J. Cohen. Procreative tourism as a last resort. Gynecol Obstet Fertil 2006;34:881-2]. PMID- 17275382 TI - Quality improvement of patient care - forensic pathologists' perspective. AB - In the U.S. today, the pathologists, both hospital-based and forensic, are regularly involved in quality assurance (QA) programs, the evaluation of patient safety at all levels of medical care, including treatments in walk-in clinics and medical offices. In the United States, official death investigations are conducted by the Medical Examiner's Office. The Medical Examiner's Office is aided in its work by a network of coordinating agencies to provide complete, comprehensive reporting and investigation of deaths placed under its jurisdiction. Those agencies are the Health Department, the Registrar of Vital Statistics on Births and Deaths, Division of Health Facilities, the Hospital Office of Decedent Affairs and the State medical licensing agencies, as well as the various law enforcement and regulatory agencies and the prosecuting attorney's office. Forensic pathologists are witnesses to the fatal results of often avoidable untoward events. They need to use their experiences to address and emphasize overall prevention programs to improve the quality of life in the community, to publicize the avoidable actions which can lead to untoward results. In the current growing atmosphere of threatening chemical, biological and radiation terrorist attacks, the health care system, especially hospitals, including emergency services, are mobilizing to develop plans to meet possible anticipated need for disaster preparedness. PMID- 17275383 TI - Timing of skin wounds. AB - Wound examination is indispensable in forensic practice. It is always necessary to determine wound vitality or wound age to correctly evaluate the relationship between death and any wounds. Thus, the determination of wound vitality or wound age is a classic but still modern theme in forensic pathology. Skin wound healing is a primitive but well orchestrated biological phenomena consisting of three sequential phases, inflammation, proliferation, and maturation. Many biological substances are involved in the process of wound repair, and this short and simplified overview of wound healing can be adopted to determine wound vitality or wound age in forensic medicine. With the development of immunohistochemistry and chemical analyses, the scientific field of wound age determination has advanced progressively during recent years. In particular, it has been demonstrated that collagens, cytokines, and growth factors are useful candidates and markers for the determination of wound vitality or age. In this review article, some interesting and instructive results are presented, contributing to the future practice of every forensic pathologist. PMID- 17275384 TI - Genetic polymorphisms of 17 Y-STRs haplotypes in Chinese Han population residing in Shandong province of China. AB - We have co-amplified (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a,b, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, and Y GATA H4) in a single PCR using the AmpFLSTR Yfiler PCR Amplification system. Allelic frequency distribution and haplotype diversity of 17 Y-chromosomal STR from a sample of 131 unrelated individuals of Chinese Han population living in Shandong province of China were obtained. A total of 129 haplotypes were observed in the 131 individuals studied, of which 127 were unique and two were found in two individuals. The gene diversity values ranged from 0.3560 (DYS391) to 0.9675 (DYS385a,b), The overall haplotype diversity for the 17 Y-STR loci was 0.9998, and the discrimination capacity was 0.9695. These results are compared with those observed in worldwide populations at both the locus and the haplotype level. PMID- 17275385 TI - Risk factors, diagnosis and prevention of sudden unexpected infant death. AB - The diagnosis of the cause of sudden unexpected infant death (SUID) is often difficult work for forensic pathologists. Its misdiagnosis or misclassification is the cause of crucial epidemiological and medicolegal problems. During the sudden infant death syndrome (SIDS) epidemic, many reports described the risk factors of SIDS as well as mechanical suffocation during sleep. Meadow's report has invited worldwide debate over whether the cause of SUID is attributable to SIDS or suffocation. On the basis of this background, the problems concerning causal diagnosis and risk factors, particularly the accidental suffocation of infants during sleep, and the specific pattern of suffocation, was reviewed from the forensic pathological viewpoint. The following tasks remain to be done for the future: (1) to avoid preventable SUIDs, the most effective measure worldwide is to identify high-risk factors for all SUIDs, including SIDS, accidental suffocation and undetermined causes, and then transmit this information to the public. (2) SIDS should be uniformly defined and diagnosed as strictly as possible to gain its reliability in the public health community and in a legal framework. PMID- 17275386 TI - VIRTOPSY - the Swiss virtual autopsy approach. AB - The aim of the VIRTOPSY project () is utilizing radiological scanning to push low tech documentation and autopsy procedures in a world of high-tech medicine in order to improve scientific value, to increase significance and quality in the forensic field. The term VIRTOPSY was created from the terms virtual and autopsy: Virtual is derived from the Latin word 'virtus', which means 'useful, efficient and good'. Autopsy is a combination of the old Greek terms 'autos' (=self) and 'opsomei' (=I will see). Thus autopsy means 'to see with ones own eyes'. Because our goal was to eliminate the subjectivity of "autos", we merged the two terms virtual and autopsy - deleting "autos" - to create VIRTOPSY. Today the project VIRTOPSY combining the research topics under one scientific umbrella, is characterized by a trans-disciplinary research approach that combines Forensic Medicine, Pathology, Radiology, Image Processing, Physics, and Biomechanics to an international scientific network. The paper will give an overview of the Virtopsy change process in forensic medicine. PMID- 17275387 TI - Early diagnosis of diffuse brain damage resulting from a blunt head injury. AB - Diffuse types of traumatic brain injury (TBI) are more difficult to diagnose than focal types in forensic postmortem examination, since macroscopic abnormalities may be minimal. In addition, most microscopic findings are not specific to TBI and are sometimes not obvious in cases when the survival period is short. Therefore, early diagnosis of diffuse TBI is most difficult. Histopathological and immunohistochemical examinations of various elements including axons, nerve cells, and glial cells in a sufficient number of blocks are indispensable. Mapping of changes in these elements with complicated focal lesions, even if the lesions are trivial, on anatomical diagrams would be useful. The combination of histopathological and immunohistochemical examinations as well as analysis of the exact history of the trauma, if possible, and elimination of other causes of death would lead to accurate diagnosis of diffuse types of TBI in cases when the survival period is brief. PMID- 17275389 TI - Genetic data from Powerplex 16 system and Identifiler kits from Buenos Aires province (Argentina). AB - Allele frequencies for the 17 autosomic STRs loci including in the PowerPlex 16 System and Identifiler were estimated from unrelated individuals living in Buenos Aires province of Argentina. PMID- 17275390 TI - The beneficial influence of ultrasound in the polymerization of epsilon caprolactam to polyamide-6 (Nylon 6). Part II: additional experiment to understand the "pre-sonication effect". AB - Ultrasound (US) "pre-sonication effect" is the beneficial effect of US in the hydrolytic polymerization of epsilon-caprolactam (CL) mixtures with very low water concentrations (about 0.1-1 wt%). It appears after a mild initial treatment of the mixtures with US [17.5-20 kHz, short times (5-15 min), low temperatures (70-110 degrees C)] followed by heating at 220-260 degrees C. An explanation is proposed on the basis of the formation in mild conditions (100 degrees C) of low concentrations of cyclic oligomers never detected in the literature at those conditions. These, under US irradiation, produce linear amino acid oligomers, which are strong activators of polymerization when the mixture of CL and water, after US irradiation, is heated at the suitable polymerization temperature indicated above. PMID- 17275391 TI - High-power ultrasound in olive paste pretreatment. Effect on process yield and virgin olive oil characteristics. AB - The effect of high-power ultrasound on olive paste, on laboratory thermo-mixing operations for virgin olive oil extraction, has been studied. Direct sonication by an ultrasound probe horn (105 W cm(-2) and 24 kHz) and indirect sonication with an ultrasound-cleaning bath (150 W and 25 kHz) were applied and their effects compared with the conventional thermal treatment. A quick-heating of olive paste, from ambient (12-20 degrees C) to optimal temperature conditions (28 30 degrees C), and an oil extractability improvement were observed when applying sonication. Better extractability was obtained by direct sonication for high moisture olives (>50%) whereas indirect sonication gave greater extractability for low moisture olive fruits (<50%). Optimal application of ultrasound was achieved with direct sonication for 4 min at the beginning of paste malaxation and with indirect sonication during the malaxation time. Effect of high-power ultrasound on oil quality parameters and nutritional and sensory characteristics were studied. Changes in quality parameters (free acidity value, peroxide value, K270 and K232) were not found, however significant effects on the levels of bitterness, polyphenols, tocopherols (vitamin E), chlorophyll and carotenoids were observed. Oils from sonicated pastes showed lower bitterness and higher content of tocopherols, chlorophylls and carotenoids. Related to sensory characteristics, off-flavour volatiles were not detected in oils from sonication treatments. Total peak areas of volatiles and the ratio hexanal/E-2-hexenal, as determined by SPME analysis, were lower than non-sonicated reference oils; sensory evaluation by panel test showed higher intensity of positive attributes and lesser of negative characteristics than those untreated. PMID- 17275392 TI - Sonochemistry on primordial Earth--its potential role in prebiotic molecular evolution. AB - Sonochemical processes are known to occur in nature and have occurred ever since there was liquid water on Earth. We advance a hypothesis that complex carbonaceous compounds, the probable precursors of life, were produced from simple primordial molecules by sonochemical processes in breaking waves of primordial seas or oceans. Our calculations show that these processes were much more common on Earth than other pathways, suggested for the formation of prebiotic complex carbonaceous compounds. The high occurrence rate of sonochemical events in breaking sea waves and the qualitative difference between sonochemical processes and other shock phenomena might have enabled formation of a variety of complex carbonaceous compounds, including amino acids, nucleotides and nucleosides, the precursors of RNA or DNA. PMID- 17275393 TI - Differentiation of Parkinson's disease and progressive supranuclear palsy with magnetic resonance imaging: the first Brazilian experience. AB - BACKGROUND: The objective of this study is to differentiate PSP from Parkinson's disease through magnetic resonance imaging. METHODS: We included 14 consecutive patients with PD (9) or PSP (5). These measures included the third ventricle, midbrain diameter, quadrigeminal plate, brainstem volumetry, and interpeduncular angle. RESULTS: Patients with PSP presented enlargement of third ventricle (100% vs. 33%), lower midbrain diameter (mean 13.2 +/- 1.7 mm vs. 16.5 +/- 1.7 mm) and thinning of the quadrigeminal plate (mean 2.7 +/- 0.3 mm vs. 3.6 +/- 0.3 mm) in comparison with PD. CONCLUSIONS: Characteristic findings on MRI may help to differentiate PD from PSP. PMID- 17275394 TI - The effect of cigarette smoking, tea, and coffee consumption on the progression of Parkinson's disease. AB - Previous epidemiological studies found a negative association between cigarette smoking, tea or coffee drinking with the occurrence of Parkinson's disease (PD). However, it is unknown how these factors affect the rate of progression of the disease. A retrospective study was conducted among 278 consecutive PD patients. Data on smoking and coffee or tea consumption were obtained through direct or proxy interviews, and the time from onset of motor symptoms until reaching Hoehn & Yahr (H&Y) stage 3 was retrieved from the case records. Cox proportional hazards model and Kaplan-Meyer model were used to estimate whether the dependent variables (smoking, drinking coffee or tea) affect the rate of progression of the disease, which was measured by the time it took patients to reach H&Y stage 3. We found that disease progression was not affected by cigarette smoking, tea or coffee consumption. The present study suggests that these variables do not have a disease modifying effect in already diagnosed PD patients. PMID- 17275396 TI - Metallocenter assembly of the hydrogenase enzymes. AB - The biosynthesis of the [NiFe]- and [FeFe]-hydrogenase enzymes requires the activities of multiple proteins that assemble the intricate metallocenters on the enzyme precursor proteins in an energy-dependent process. These accessory proteins include enzymes that synthesize the non-protein iron ligands as well as metallochaperones for the delivery of nickel to the [NiFe]-hydrogenase. Over the past few years many of these proteins have been examined in vitro. The biochemical properties, in the context of the earlier genetic studies, provide a basis for assigning function to the individual accessory proteins and mapping out the sequential steps of the metallocenter assembly pathways. This framework will serve as a foundation for detailed mechanistic analysis of these complex biomolecular factories. PMID- 17275395 TI - ELISA reveals a difference in the structure of substantia nigra ferritin in Parkinson's disease and incidental Lewy body compared to control. AB - Iron released from ferritin may trigger oxidative stress leading to progressive neurodegeneration of substantia nigra resulting in Parkinson's disease (PD). Change in the structure of ferritin may allow an easier efflux of iron. We compared with the use of ELISA the structure of ferritin (concentrations of H and L ferritins) in substantia nigra (SN) in ten cases of PD, six of incidental Lewy body (ILB) cases and 20 controls. SN concentration of L ferritin in ILB (50.6+/ 11.5 ng/mg) and in PD (52.5+/-26.0) was lower than in control (97.9+/-54.9). H ferritin in PD (534.2+/-223.1) was higher than in ILB (336.9+/-87.7) and control (374.8+/-169.3). The decrease of L ferritin in SN in PD and ILB may suggest that the whole process of neurodegeneration starts with a higher availability of free iron, which is released from the ferritin shell. PMID- 17275397 TI - Flavoenzymes. AB - Flavoenzymes are colourful oxidoreductases that catalyze a large variety of different types of reactions. Flavoenzymes have been extensively studied for their structural and mechanistic properties and are gaining momentum in industrial biocatalytic applications. Some of these enzymes catalyze the oxidative modification of protein substrates. New insights in oxidative flavoenzymes and in particular in novel family members point towards their potential application in the pharmaceutical, fine-chemical and food industries. PMID- 17275398 TI - Differential behavior of sPLA2-V and sPLA2-X in human neutrophils. AB - Neutrophils and differentiated PLB-985 cells contain various types of PLA(2)s including the 85 kDa cytosolic PLA(2) (cPLA(2)), Ca(2+)-independent PLA(2) (iPLA(2)) and secreted PLA(2)s (sPLA(2)s). The present study focuses on the behavior of sPLA(2)s in neutrophils and PLB cells and their relationship to cPLA(2)alpha. The results of the present research show that the two types of sPLA(2) present in neutrophils, sPLA(2)-V and sPLA(2)-X, which are located in the azurophil granules, are differentially affected by physiological stimuli. While sPLA(2)-V is secreted to the extacellular milieu, sPLA(2)-X is detected on the plasma membranes after stimulation. Stimulation of neutrophils with formyl-Met Leu-Phe (fMLP), opsonized zymosan (OZ) or A23187 resulted in a different kinetics of sPLA(2) secretion as detected by its activity in the neutrophil supernatants. Neutrophil priming by inflammatory cytokines or LPS enhanced sPLA(2) activity detected in the supernatant after stimulation by fMLP. This increased activity was due to increased secretion of sPLA(2)-V to the supernatant and not to release of sPLA(2)-X. sPLA(2) in granulocyte-like PLB cells exhibit identical characteristics to neutrophil sPLA(2), with similar activity and optimal pH of 7.5. Granulocyte-like cPLA(2)alpha-deficient PLB cells serve as a good model to study whether sPLA(2) activity is regulated by cPLA(2)alpha. Secretion and activity of sPLA(2) were found to be similar in granulocyte-like PLB cells expressing or lacking cPLA(2)alpha, indicating that they are not under cPLA(2)alpha regulation. PMID- 17275399 TI - Unique cardiopulmonary exercise test responses in overweight middle-aged adults with obstructive sleep apnea. AB - BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive nighttime obstructions of the upper airway that induce hypoxemia, hypercapnia, sympathetic activation, and arousals. This disorder induces cardiovascular autonomic imbalance and contributes to the development of hypertension. While the diagnostic and prognostic utility of exercise testing is well established in cardiology, the clinical utility of the exercise test in screening for OSA has not been carefully explored. To explore this potential application, we contrasted cardiopulmonary responses to exercise testing in patients recently diagnosed with OSA with apparently healthy counterparts of similar physical inactivity history, age, and body habitus. METHODS: Twenty-three normotensive overweight adults with OSA [apnea-hypopnea index (AHI)=24.7+/-13.5 events h(-1); body mass index (BMI)=33.1+/-5.5 kg m(-2); age=45.6+/-10.7 years] and nine apparently healthy controls of similar age and morphology (BMI=29.5+/-5.5 kg m(-2); age=40.2+/-8.1 years; AHI=4.9+/-0.1) completed a maximal ramping cardiopulmonary exercise tolerance test on a cycle ergometer. Measures included oxygen consumption (VO(2)pk), ventilation (V(E)), heart rate (HR), blood pressure (BP), cardiac output (Qc), and stroke volume (SV). RESULTS: Age, BMI, rest HR, rest BP, rest and exercise cardiac index (QI), rest and exercise stroke volume index (SVI), and V O(2)pk were not different between OSA patients and controls (p>0.05). Exercise heart rate was significantly lower and diastolic BP higher in the OSA group (p<0.05). In the physically active recovery (low-load pedaling), systolic BP recovery was delayed (p<0.05) in the OSA group while diastolic BP tended to remain higher (p=0.056). CONCLUSION: Patients with OSA have a distinctive response to graded exercise, characterized by a blunted HR response, markedly delayed systolic BP response in early recovery, and elevated diastolic BP in both exercise and early recovery. Clinical trials are justified to determine the clinical utility of graded exercise testing to independently inform clinical decision-making for triaging patients to diagnostic polysomnography. PMID- 17275400 TI - Modulation of upper and lower esophageal sphincter tone during sleep. AB - BACKGROUND AND PURPOSE: The pressures generated within the upper esophageal sphincter (P(UES)) and lower esophageal sphincter (P(LES)) reflect the integrity of these barriers to gastroesophageal and pharyngoesophageal reflux, respectively. This study sought to describe the effects of sleep, respiration and posture on the function of the UES and the LES and the pressure differentials developed across them. METHODS: Ten healthy volunteers (7M, 3F: 38+/-10 yr) without a history of sleep-disordered breathing or reflux underwent overnight polysomnography with simultaneous measurement of P(LES) and P(UES) using a purpose-built sleeve device (Dentsleeve). Posture was recorded but not controlled. RESULTS: Subjects slept for 4.3+/-1.6h. Compared to waking values, both end-inspiratory and end-expiratory Pues were significantly less during slow wave sleep (SWS) (p<0.05). However, P(LES) was unaffected by sleep stage. During wakefulness and all stages of sleep, both P(UES) and P(LES) were greater at end inspiration than end-expiration (p<0.05). Similar relationships were observed whether subjects were supine or in the lateral decubitus position. CONCLUSION: Sleep decreases the effectiveness of the UES to act as a barrier to pharyngoesophageal reflux, particularly during slow wave sleep (SWS). UES pressure varies with respiration, with minimal values observed during expiration. Hence, barrier function of the UES appears most impaired during SWS, in the expiratory phase of the respiratory cycle. The LES pressure and its barrier pressure also vary with respiration, being least during expiration. However, unlike the UES, the function of the LES was unaffected by sleep. PMID- 17275402 TI - Disturbed perception of wakefulness within sleep: a new sleep disorder or the extreme end of a spectrum. PMID- 17275401 TI - Genetic susceptibility to obstructive sleep apnea in the obese child. AB - The etiology of obstructive sleep apnea (OSA) is multifactorial, consisting of a complex interplay between anatomic and neuromuscular factors and an underlying genetic predisposition toward this disease. Several of the factors that have been reported to play a role in the pathogenesis of OSA can serve as intermediate phenotypes in investigations targeting genetic susceptibility to OSA. A precise underpinning of the genetic basis of OSA has been thus far difficult because it is still unknown whether or not the recognized candidate genes for OSA are directly causal to the phenotype, or whether their effects on OSA are mediated through the intermediate phenotypes of OSA. Future studies utilizing phenotypically homogenous groups such as those with childhood OSA and technological advances such as haplotype analysis in a case control design are extremely promising. Developing predictive models that incorporate genetic and phenotypic markers will enable early diagnosis and, therefore, intervention, ultimately resulting in reduction of morbidity and of the public health concerns associated with OSA in obese children. PMID- 17275403 TI - Integrated selective: an innovative teaching strategy for sleep medicine instruction for medical students. AB - OBJECTIVES: Sleep disorders are common among all age groups, but repeated studies have demonstrated that physicians underdiagnose sleep disorders. Lack of curriculum time and the limited number of faculty with expertise in sleep medicine have been cited as major barriers for sleep medicine instruction. This paper describes the development, implementation, and evaluation of an integrated selective in sleep medicine for fourth-year medical students. METHODS: A one month required fourth-year integrated selective in sleep medicine was implemented at Medical College of Wisconsin (MCW). A curriculum was developed, incorporating core competencies of sleep medicine and using a combination of instructional strategies. Three sources of data were used to evaluate the selective: an elective-specific questionnaire, learner ratings, and performance on a pre- and post-knowledge test. RESULTS: Twenty medical students (13 male; 7 female) have completed the selective to date. Lack of exposure to sleep medicine during the first three years of medical school was the most common reason for taking the elective. Student evaluation of the rotation averaged 1.5 on a five-point scale (1=best), above the average for fourth-year rotations. The mean examination scores increased significantly from pre- (56%) to post- (86%) selective (p<.05). Unanticipated but associated positive outcomes included (a) an invitation to teach a 1h lecture to third-year medical students and pediatric residents, (b) a 2h workshop on sleep medicine for internal medicine residents, and (c) grant funding from the medical college's Curriculum and Evaluation Committee to support the development of on-line sleep medicine instruction. CONCLUSIONS: A well designed fourth-year integrated selective improves student knowledge in sleep medicine and may provide an opening for additional inclusion of sleep medicine instruction for various trainees. PMID- 17275404 TI - Magnesium not likely to play a major role in the pathogenesis of Restless Legs Syndrome: serum and cerebrospinal fluid studies. PMID- 17275405 TI - Restless legs syndrome in narcolepsy: a side effect of sodium oxybate? AB - Gamma-hydroxybutyrate (GHB) has re-emerged as a major treatment for narcolepsy. As dopaminergic transmission is clearly involved in the pathophysiology of restless legs syndrome (RLS), and GHB reduces dopamine release, one may hypothesize that RLS may occur in narcolepsy in the presence of GHB. We report a case of narcolepsy with a severe occurrence of typical RLS with GHB, symptoms never previously experienced by the subject and reversible after withdrawal. PMID- 17275406 TI - Actigraphy in irregular sleep-wake rhythm. PMID- 17275407 TI - Positive sleep state misperception - a new concept of sleep misperception. AB - OBJECTIVES: To better define the concept of sleep misperception and analyse a category of patients who overestimate their sleep. At present, a condition of underestimation of sleep is classified as paradoxical insomnia. Overestimation of sleep has also been reported in the past, with no clear reference to corresponding polysomnographic (PSG) findings or its clinical significance. PATIENTS AND METHODS: Patients were recruited from the general population undergoing a PSG assessment for a cross-sectional retrospective study in a sleep clinic affiliated with a tertiary health center. RESULTS: A group of patients who overestimated their sleep had mostly non-discriminating PSG findings when compared to patients who underestimated their sleep, and correct estimators. The only parameters that were significantly different were objective sleep duration and efficiency, and, importantly, respective multiple sleep latency test (MSLT) results. The patients who overestimated their sleep had a mean MSLT result of 7.8 min, which indicates moderate daytime sleepiness. Patients who underestimated their sleep and correct estimators had the respective MSLT results of >10 min, making a statistically significant difference. CONCLUSION: The authors identified a condition opposite the previously described sleep underestimation, and named it 'positive sleep state misperception' (PSSM). The condition is characterised by a gross overestimation of sleep. Inadequate sleep results in a clinically significant excessive daytime sleepiness, which patients were not able to predict. The authors propose a new model that incorporates both ends of the sleep misperception spectrum. PMID- 17275408 TI - Esophageal function during sleep: another danger in the night. PMID- 17275409 TI - A restless legs syndrome (RLS) case: diagnosis relevance. PMID- 17275410 TI - Human biomonitoring activities--programmes by industry. AB - Biomonitoring of exposure to chemicals has been practiced for over half a century on a regular basis. During the last decade, however, the focus changed from occupational to environmental settings, requiring a different interpretative framework. Under the auspices of the European Centre for Ecology and Ecotoxicology (ECETOC) a framework was developed that allows to assess the relevance of any biomonitoring result to be interpreted reliably. If biomonitoring data is to be used for the evaluation of health risks of a substance, information is required on the analytical integrity of the data, the toxicokinetics of this substance, and its health effects in relation to (low) exposures. In addition, a weight-of-evidence needs to be used. The framework also identifies a number of data-gaps, several of which are addressed through the Long range Research Initiative (LRI), an initiative of the global chemical industries (EU, USA, and Japan), which aims to help answering important questions in the application of biomonitoring data in human health risk assessment. PMID- 17275411 TI - The potential of cardiac stem cell therapy for heart failure. AB - Cardiac failure is characterised by the loss of cardiomyocytes, and several strategies to replace the lost cell mass are being developed. Animal models have demonstrated the therapeutic potential of several cell types, and both autologous skeletal myoblasts and bone marrow progenitor cells have been tested in preliminary clinical trials. However functional improvements have been modest and the mechanism of benefit is unclear, although myocardial regeneration is not a significant factor. Alternative strategies using autologous resident cardiac progenitor cells or embryonic stem cell-derived cardiomyocytes could recreate de novo myocardium with higher efficiency, although various hurdles must be overcome before these strategies are translated to the clinic. PMID- 17275412 TI - SMILES as an alternative to the graph in QSAR modelling of bee toxicity. AB - Simplified Molecular Input Line Entry System (SMILES) nomenclature has been used as elucidating the molecular structure in construction of the quantitative structure-activity relationships (QSAR) for predicting bee toxicity. On the basis of the symbols used in the SMILES notation numerical parameters have been obtained, which are simple and fast to calculate. The method has been used to develop a QSAR model to predict toxicity of pesticides on bees. Results on a heterogeneous set of pesticides are good. Statistical characteristics of this model are: n=85, R2=0.68, s=0.82, F=180 (training set); n=20, R2=0.72, s=0.68, F=46 (test set). PMID- 17275413 TI - Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis. AB - B cell depletion may affect T cell activation and costimulation status in rituximab-treated patients with SLE. We examined whether rituximab administration in patients with active lupus nephritis is related to changes in mRNA expression of genes that define regulatory T cells (Tregs) in peripheral blood lymphocytes, measured by real-time PCR. At the early phase of B cell depletion mRNA levels of CD25, CTLA-4, GITR and the bona fide Treg functional marker FOXP3 increased significantly in all 7 patients examined. In contrast, mRNA levels of the costimulatory/activation T cell molecule CD40L were profoundly reduced, while mRNA levels of TGF-beta, a cytokine contributing to Treg induction, increased significantly in all. During follow-up, increased FOXP3 mRNA persisted in those patients in clinical remission, while in those patients with active disease subsequent decreases were noted. Further studies should examine whether modulation of Tregs by therapeutic B cell depletion contributes and/or predicts lupus disease remission. PMID- 17275414 TI - Serum and BAL macrophage migration inhibitory factor levels in HIV infected Tanzanians with pulmonary tuberculosis or other lung diseases. AB - Macrophage migration inhibitory factor (MIF) activates macrophages, promotes delayed-type hypersensitivity reaction, and regulates Th1/Th2 balance in inflammatory response. Serum MIF concentration is high in patients with pulmonary tuberculosis (PTB). Higher MIF levels are associated with high mortality. No study has addressed MIF levels and its role in PTB/HIV-co infection. We determined serum and BAL MIF levels in Tanzanian HIV-infected patients with and without PTB, and correlated the levels with 1-month outcome. We compared with serum MIF levels of HIV seronegative patients with PTB and of healthy controls. All HIV-infected patients irrespective of PTB infection had significantly higher serum MIF levels than HIV-seronegative patients with PTB, and than healthy controls. In HIV seropositive patients low serum MIF levels were associated with high 1-month mortality. In conclusion, HIV infection was associated with elevated serum MIF levels regardless of PTB. Low serum MIF levels were associated with high mortality. PMID- 17275416 TI - Ethnic differences regarding tactile and pain thresholds in the trigeminal region. AB - The aim of the present study was to evaluate ethnic differences of the tactile detection threshold (TDT), the filament-prick pain detection threshold (FPT), the pressure pain detection threshold (PPT), and the pressure pain tolerance detection threshold (PTOL) in the orofacial region of symptom-free subjects. Twenty-two men and 22 women in Belgium and in Japan (age range from 20 to 31 years) participated. The TDT and the FPT were measured on the cheek skin (CS) overlying the masseter muscles (MM), on the maxillary gingiva (MG), and at the tip of the tongue (TT), using Semmes-Weinstein monofilaments. The PPT and PTOL were measured at the central part of the MM, using a pressure algometer. A general linear model was used in each case to capture ethnic and gender effects. Japanese women had the lowest TDT at CS, in contrast to Belgian men, who had the highest value; a significant ethnic and gender effect was found (P=.026 and P<.001, respectively). Similar results were found for FPT at CS with significant ethnic and gender effects (P<.001 for both). There was no significant ethnic effect regarding intra-oral TDT and FPT or regarding PPT and PTOL. PERSPECTIVE: Our findings clearly indicate that future studies of tactile and pain measurements need to standardize and control for gender and ethnicity. Further, a comprehensive evaluation of results from various stimulation modalities may better clarify the pain mechanisms and gender/ethnic characteristics, as well as comparisons between normal subjects and patients. PMID- 17275415 TI - Soluble TNF-alpha receptor 2 produced by alternative splicing is paradoxically associated with markers of liver injury. AB - Tumor necrosis factor-alpha and insulin resistance play central roles in the pathogenesis of abnormal hepatocellular function. We evaluate the relationship between a novel serum DS-TNFR2 (an alternatively spliced soluble TNF-alpha receptor 2) isoform and parameters of liver health. Serum ALT, AST and GGT, insulin resistance, adiponectin and DS-TNFR2 isoform concentrations were measured in 492 subjects from two different Caucasian Spanish populations. We found a significant negative association between serum ALT and DS-TNFR2 levels in both populations (r=-0.269; p=0.002 and r=-0.152; p=0.01, respectively). DS-TNFR2 levels also correlated negatively with serum AST (r=-0.142; p=0.042) and GGT (r= 0.206; p=0.003) in population 1 and with AST (r=-0.127; p=0.038) in population 2. In multiple regression analysis models, serum DS-TNFR2 was shown to be an independent modulator of serum ALT activity after adjusting for sex, age, BMI, HOMA and adiponectin in both populations. These results suggest potential anti inflammatory properties of this TNF-alpha receptor 2 isoform at the hepatic level. PMID- 17275417 TI - Adolescent self-perception: associations with chronic musculoskeletal pain and functional disability. AB - Associations among pain, functional disability, and self-perceived competence were examined in a retrospective record review of the initial clinical evaluations of 115 adolescents (ages 13 to 18 years) with chronic musculoskeletal pain not associated with a specific organic cause. Adolescents self-reported on pain intensity, functional disability, and 9 developmentally relevant domains of self-perceived competence, using the Self-Perception Profile for Adolescents (Harter, 1988). Results confirmed a relation between usual pain intensity and functional disability (r = 0.47, P < .001). A series of multiple regression analyses revealed that adolescents' perceptions of global self-worth significantly moderated the relation between pain and disability. These findings extend our understanding of the relations among self-perception, chronic pain, and disability to include adolescents with chronic musculoskeletal pain syndromes and have future research and therapeutic implications. PERSPECTIVE: Adolescents with chronic pain syndromes can face significant challenges in accomplishing developmental goals with respect to the pain and disability they experience. Perceptions of self-worth appear to play an important role in understanding the relation between pain and functional disability among adolescents with chronic pain. PMID- 17275418 TI - Summary statement IV: Obesity and diabetes: opportunities for translation of basic research. AB - The worldwide epidemics of obesity and diabetes that have emerged in the 21st century are creating a major public heath problem, having struck developed countries as well as those still developing. With our present clinical tools, abilities, and understanding, we may not be prepared to respond adequately to the demands or be able to engage in effective prevention strategies. The underlying pathophysiological reasons for the increases in both obesity and diabetes may be closely related through abnormality in endothelial cells. Diverse expertise from within and outside the public health arena will be needed to explore the health implications from an "endothelium" perspective and identify those at risk for the development of chronic disease. Identification of new biological markers and better measures of current biological marker will both be critical in understanding and addressing the ongoing epidemic of chronic diseases. PMID- 17275419 TI - Emphysematous cholecystitis. PMID- 17275422 TI - A model for triplet mutation formation based on error-prone translesional DNA synthesis opposite UV photolesions. AB - A triplet mutation is defined as multiple base substitutions or frameshifts within a three-nucleotide sequence which includes a dipyrimidine sequence. Triplet mutations have recently been identified as a new type of UV-specific mutation, although the mechanism of their formation is unknown. A total of 163 triplet mutations were identified through an extensive search of previously published data on UV-induced mutations, including mutations from skin, skin cancer, and cultured mammalian cells. Seven common patterns of sequence changes were found: Type I, NTC-->TTT; Type IIa, NCC-->PyTT or PyCT (Py, pyrimidine); Type IIb, TCC-->PuTT or PuCT (Pu, purine); Type III, NCC-->NAT or NTA; Type IV, NTT-->AAT; Type Va, NCT-->NTX; and Type Vb, PuCT-->XTT (N and X, independent anonymous bases). Furthermore, it is suggested that the type of UV lesion responsible for each of these triplet mutation classes are (a) pyrimidine(6 4)pyrimidone photoproducts for Types I, IIb, III, IV and Vb, (b) cyclobutane pyrimidine dimers for Type Va, and (c) Dewar valence isomers for Types IIa and IIb. These estimations are based primarily on results from previous studies using photolyases specific for each type of UV lesion. A model is proposed to explain the formation of each type of triplet mutation, based on error-prone translesional DNA synthesis opposite UV-specific photolesions. The model is largely consistent with the 'A-rule', and predicts error-prone insertions not only opposite photolesions but also opposite the undamaged template base one nucleotide downstream from the lesions. PMID- 17275421 TI - Phylogenetic analysis of the promoter region of the CD40L gene in primates and other mammals. AB - CD40L is a type II membrane protein comprised of 261 amino acids. CD40L plays a crucial role in the immune system where it is primarily expressed on activated T cells and triggers immunoglobulin class switching. The genetic disease X-linked hypergammaglobulinemia (HIGM1, XHIGM or XHIM) is caused by mutations in the CD40L gene. Individuals with HIGM1 are susceptible to recurrent infections to pathogens and a relationship has been shown to exist with malaria [Sabeti, P., Usen, S., Farhadian, S., Jallow, M., Doherty, T., Newport, M., Pinder, M., Ward, R., Kwiatkowski, D., 2002a. CD40L association with protection from severe malaria. Genes Immun. 3, 286-291]. In this paper, we phylogenetically examine the promoter region of CD40L in primates and other mammals via phylogenetic shadowing. This analysis revealed several regions of the CD40L promoter that were highly constrained and thereby inferred to be functional. These constrained regions confirmed many known regulatory sites. In addition, a novel, highly constrained upstream region was also identified which had an NF-AT recognition motif. These analyses also showed that the different mammal groups do not share an exactly similar set of promoter binding sites and taxon-specific promoters have evolved. PMID- 17275420 TI - Parasympathetic stimulation elicits cerebral vasodilatation in rat. AB - Forebrain arteries receive nitroxidergic input from parasympathetic ganglionic fibers that arise from the pterygopalatine ganglia. Previous studies have shown that ganglionic stimulation in some species led to cerebral vasodilatation while interruption of those fibers interfered with vasodilatation seen during acute hypertension. Because the ganglionic fibers are quite delicate and are easily damaged when the ganglia are approached with published techniques we sought to develop a method that allowed clear exposure of the ganglia and permitted demonstration of cerebral vasodilatation with electrical stimulation of the ganglia in the rat. We had found that an orbital approach during which the eye was retracted for visualization of the ganglion precluded eliciting vasodilatation with ganglionic stimulation. In the current study approaching the ganglion through an incision over the zygomatic arch provided clear exposure of the ganglion and stimulation of the ganglion with that approach led to vasodilatation. PMID- 17275424 TI - H pylori re-infection in type 1 diabetes: a 5 years follow-up. PMID- 17275425 TI - International experience on the use of artificial neural networks in gastroenterology. AB - In this paper, we reconsider the scientific background for the use of artificial intelligence tools in medicine. A review of some recent significant papers shows that artificial neural networks, the more advanced and effective artificial intelligence technique, can improve the classification accuracy and survival prediction of a number of gastrointestinal diseases. We discuss the 'added value' the use of artificial neural networks-based tools can bring in the field of gastroenterology, both at research and clinical application level, when compared with traditional statistical or clinical-pathological methods. PMID- 17275423 TI - An optimized analytical method of fluconazole in human plasma by high-performance liquid chromatography with ultraviolet detection and its application to a bioequivalence study. AB - A sensitive and accurate HPLC-UV method for the quantification of fluconazole (FLA) level in human plasma has been developed. The sample was prepared by one step liquid-liquid extraction (LLE) of FLA from plasma using dichloromethane. Phenacetin was used as the internal standard. The chromatographic retention times of FLA and phenacetin were 4.6 and 8.3 min, respectively. The lower limit of quantitation (LLOQ) was 0.05 microg/mL, and no interferences were detected in the chromatograms. The devised HPLC-UV method was validated by evaluating its intra- and inter-day precisions and accuracies in a linear concentration range between 0.05 and 10.00 microg/mL. The devised method was successfully applied to a bioequivalence studies involving the oral administration of a single 150 mg FLA tablet and 3 x 50 mg FLA capsules in healthy Korean male volunteers. PMID- 17275427 TI - Is there a downgrading in the alert about the hepatitis B virus infection in Italy? AB - BACKGROUND AND AIM: There is suspicion of a decrease in warning regarding the hepatitis B virus as a health problem both by the infected individuals and their doctors. The aim of this study was to investigate whether the clinical/virology investigation of chronic hepatitis B virus infected individuals is at present accurate. METHODS: The chronic hepatitis B virus surface antigen carriers consecutively attending 13 different hospital divisions in Calabria from July to December 2005 were evaluated to investigate the available information on the grade of their liver disease, their virologic profile and the hepatitis B virus status of their family members. RESULTS: Four-hundred-thirty hepatitis B virus surface antigen positive individuals were enrolled, 417 of whom were Calabrians. Most of them had a diagnosis of chronic liver disease, but a liver biopsy had been performed only in 13.5% of the cases, whereas more than 1/3 of them had not been tested for hepatitis Delta virus co-infection. The majority of these individuals were unaware of the hepatitis B virus status of their family members. Moreover, anti-hepatitis B virus vaccination procedures were not performed in most of the hepatitis B virus surface antigen carrier families. CONCLUSIONS: This study revealed that fundamental clinical, virological, and epidemiological aspects of chronic hepatitis B virus infection are not investigated in many hepatitis B virus surface antigen carriers, suggesting that the general knowledge as regards hepatitis B virus is mostly inadequate. PMID- 17275426 TI - Extracorporeal shock wave lithotripsy for clearance of refractory bile duct stones. AB - BACKGROUND AND STUDY AIMS: Following endoscopic sphincterotomy, 90% of bile duct stones can be removed with a Dormia basket or balloon catheter. The removal can fail in patients with large stones, intrahepatic stones, bile duct strictures or a difficult anatomy. The aim of this retrospective study is to investigate the efficacy and safety of extracorporeal shock wave lithotripsy in fragmenting and allowing the extraction of bile duct stones that could not be cleared by routine endoscopic means including mechanical lithotripsy. PATIENTS AND METHODS: From 1989 to January 2005, we treated with extracorporeal shock wave lithotripsy 376 patients (133 males and 243 females, median age 71.4 years) with bile duct stones that were not removable following endoscopic sphincterotomy, using the extracorporeal shock wave lithotripsy Lithostar Plus machine built by Siemens Co. of Erlangen, Germany. Stone targeting was performed fluoroscopically following injection of contrast via nasobiliary drain or T-tube in 362 patients and by ultrasonography in eight patients. Residual fragments were cleared at endoscopic retrograde cholangiopancreatograhy. Two hundred and ten of the 370 patients treated (56.7%) showed only 1 stone, 57 (15.4%) showed 2, 45 (12.1%) showed 3, 58 (15.6%) showed more than 3 stones. The median diameter of the stones was 21mm (range 7-80mm). RESULTS: Complete stone clearance was achieved in 334 of the 376 patients who underwent the extracorporeal shock wave lithotripsy procedure (90.2%). Six patients (1.5%) dropped out of treatment during their first sessions, mainly because of intolerance. Each patient averaged 3.7 treatments (1 12), at an average rate of 3470 shocks per session (1500-5400), at an average energy level of 3.4mJ (1-7). Complications were recorded in 34 patients (9.1%); 22 patients experienced symptomatic cardiac arrhythmia, 4 haemobilia, 2 cholangitis, 3 haematuria, 3 dyspnoea; no deaths were associated with the procedure. CONCLUSIONS: Extracorporeal shock wave lithotripsy is a safe and effective therapy in those patients in whom endoscopic techniques have failed with a clearing rate of 90.2% of refractory bile duct stones with a low rate of complications. PMID- 17275428 TI - Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceral transplantation: A comparison of two different regimens on 29 recipients during the early post-operative period. AB - INTRODUCTION: Induction therapy has been recently adopted for intestinal transplant. PATIENTS AND METHODS: We compared during first 30 days post transplantation 29 recipients, allocated in two groups, treated with Daclizumab (Zenapax) or Alemtuzumab (Campath-1H). RESULTS: During first month, 45% of Daclizumab recipients experienced six acute cellular rejections (ACRs) of mild degree, while 63% of them developed an infection requiring treatment. We found three acute cellular rejections in 17.6% of Alemtuzumab recipients, two with moderate degree; 64.7% of them required treatment for infection. DISCUSSION AND CONCLUSIONS: Graft and patient 3-years cumulative survival rate were not significantly different between groups. Alemtuzumab seems to offer a better immunosuppression during first month. PMID- 17275429 TI - Synthesis and characterization of both ionically and enzymatically cross-linkable alginate. AB - Alginate with phenol moieties in the polymer side chains was synthesized through the conjugation reaction of alginate and tyramine. Immersing an aqueous solution of the alginate containing horseradish peroxidase into a solution containing H(2)O(2) caused the solution to gel via peroxidase-catalyzed oxidative coupling of the phenols. In addition, alginate prepared under appropriate reaction conditions retained the attractive properties associated with unmodified alginate; spherical gel beads were formed by dropping an aqueous alginate solution (1.0wt.%) into a solution containing calcium ions. The oxidative coupling of the phenols was effective for suppressing the destabilization of the alginate gel resulting from a loss of bonding between the divalent cations and alginate. The mechanical properties of the resultant gels were influenced by the preparation conditions of the alginate and the type of cross-linking. PMID- 17275430 TI - Cytotoxic effects of aggregated nanomaterials. AB - This study deals with cytotoxicity assays performed on an array of commercially manufactured inorganic nanoparticulate materials, including Ag, TiO(2), Fe(2)O(3), Al(2)O(3), ZrO(2), Si(3)N(4), naturally occurring mineral chrysotile asbestos and carbonaceous nanoparticulate materials such as multiwall carbon nanotube aggregates and black carbon aggregates. The nanomaterials were characterized by TEM, as the primary particles, aggregates or long fiber dimensions ranged from 2nm to 20microm. Cytotoxicological assays of these nanomaterials were performed utilizing a murine alveolar macrophage cell line and human macrophage and epithelial lung cell lines as comparators. The nanoparticulate materials exhibited varying degrees of cytoxicity for all cell lines and the general trends were similar for both the murine and human macrophage cell lines. These findings suggest that representative cytotoxic responses for humans might be obtained by nanoparticulate exposures to simple murine macrophage cell line assays. Moreover, these results illustrate the utility in performing rapid in vitro assays for cytotoxicity assessments of nanoparticulate materials as a general inquiry of potential respiratory health risks in humans. PMID- 17275433 TI - Positron emission tomography in the diagnosis of muscular sarcoidosis. PMID- 17275435 TI - Quality management and health care. PMID- 17275436 TI - There are more confounders in omeprazole-calcium interaction. PMID- 17275432 TI - CREM deficiency in mice alters the response of bone to intermittent parathyroid hormone treatment. AB - CREM belongs to the ATF/CREB family of basic leucine zipper transcription factors. We previously showed that PTH induces ICER (inducible cAMP early repressor) in osteoblasts. ICER proteins, which are transcribed from the P2 promoter of the Crem gene, act as transcriptional attenuators. The objective of this study was to determine whether the Crem gene plays a role in the response of bone to intermittent PTH. Adult Crem knockout (KO) and wild type (WT) male mice were given daily subcutaneous injections of vehicle or hPTH(1-34) (160 mug/kg) for 10 days. Bone mineral content and density (BMC and BMD, respectively) were measured in femur and tibia by dual energy X-ray absorptiometry (DEXA). Bone morphometry was analyzed by X-ray computed microtomography (microCT) and histomorphometry. Serum bone turnover markers were measured. In vitro osteoclast formation assays were performed in bone marrow cultures treated with PTH or the combination of RANKL and M-CSF. KO mice had slightly higher basal bone mass than wild type mice. PTH treatment increased tibial BMC and BMD to a greater extent in WT mice compared to KO mice. PTH increased both cortical area and trabecular bone area in WT but not in KO femurs. PTH increased the bone formation rate and percent osteoblast surface to the same extent in femurs of WT and KO mice but increased osteoclast parameters and calvarial porosity to a greater extent in KO mice. PTH increased serum osteocalcin levels to the same extent in WT and KO mice. PTH-induced osteoclast formation was 2-fold greater in bone marrow cultures from KO mice. Collectively, our data suggest that the CREM deficiency in mice alters the response of bone to intermittent PTH treatment such that osteoclastogenesis is increased. Crem gene may specify the anabolic response to intermittent PTH treatment by restraining PTH-induced osteoclastogenesis. PMID- 17275437 TI - Reply to "dissection of the internal carotid artery and hemicraniectomy". PMID- 17275439 TI - A word on chills. PMID- 17275441 TI - Look, feel, listen or look, listen, feel? PMID- 17275444 TI - Management of menopausal symptoms. PMID- 17275442 TI - Laryngeal neuropathy as a cause of chronic intractable cough. PMID- 17275445 TI - Are stem cells and genetic therapies ready for "prime time"? PMID- 17275446 TI - Assessing and treating depression in primary care medicine. AB - Depression, a common and disabling condition, is often misunderstood by patients, family members, and clinicians. It is frequently underdiagnosed and untreated or inadequately treated. Criteria for major depressive disorder are listed in the DSM-IV-TR, but even less severe depression may merit intervention--especially if chronic. Our understanding of the etiology of depression is rudimentary, but it may involve multiple genes combined with negative life experiences. A variety of pharmacologic and psychosocial treatments are available for treating depression. Most patients who are well treated can be relieved of symptoms and return to full function. PMID- 17275447 TI - Management of post-myocardial infarction patients with left ventricular systolic dysfunction. AB - After a myocardial infarction (MI), patients are at risk for reinfarction, heart failure (HF), and sudden death. This risk is much higher in patients with left ventricular systolic dysfunction (LVSD). Although post-MI patients with LVSD have an even greater risk of mortality and morbidity, they had been generally excluded from clinical trials. This article reviews recent clinical trials that included post-MI patients with LVSD with or without signs and symptoms of HF. These trials have defined the benefits of pharmacologic management and device therapy in patients who survive an MI in the presence of LVSD. PMID- 17275448 TI - Diagnostic and therapeutic approach to acute decompensated heart failure. AB - Heart failure afflicts large numbers of patients and is the leading cause for hospitalizations in the United States. Diagnosis and management of decompensated heart failure present a clinical challenge, requiring complex decision-making. History and physical examination findings are important in the diagnosis of heart failure. Diagnostically, B-type natriuretic peptide levels appear very useful to separate cardiac from noncardiac causes of dyspnea and provide information about heart failure severity and prognosis. Immediate management goals include improvement of symptoms and hemodynamic parameters. Diuretics, vasodilators, and inotropic agents are useful in the acute setting. This article provides a systematic approach to the diagnosis and management of acute decompensated heart failure. PMID- 17275449 TI - Polycystic ovary syndrome: diagnosis and treatment. AB - Polycystic ovary syndrome affects 6%-7% of reproductive-aged women, making it the most common endocrine disorder in this population. It is characterized by chronic anovulation and hyperandrogenism. Affected women may present with reproductive manifestations such as irregular menses or infertility, or cutaneous manifestations, including hirsutism, acne, or male-pattern hair loss. Over the past decade, several serious metabolic complications also have been associated with polycystic ovary syndrome including type 2 diabetes mellitus, metabolic syndrome, sleep apnea, and possibly cardiovascular disease and nonalcoholic fatty liver disease. In addition to treating symptoms by regulating menstrual cycles and improving hyperandrogenism, it is imperative that clinicians recognize and treat metabolic complications. Lifestyle therapies are first-line treatment in women with polycystic ovary syndrome, particularly if they are overweight. Pharmacological therapies are also available and should be tailored on an individual basis. This article reviews the diagnosis, clinical manifestations, metabolic complications, and treatment of the syndrome. A table summarizing treatment recommendations is provided. PMID- 17275450 TI - A pain in the belly. PMID- 17275451 TI - Scarce among men. PMID- 17275452 TI - After the injury. PMID- 17275453 TI - A gut reaction? PMID- 17275454 TI - VT or not VT? PMID- 17275455 TI - Nearly 90 degrees from normal. PMID- 17275456 TI - Prevalence and risk factors for erectile dysfunction in the US. AB - PURPOSE: To assess the prevalence of erectile dysfunction and to quantify associations between putative risk factors and erectile dysfunction in the US adult male population. METHODS: Cross-sectional analysis of data from 2126 adult male participants in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). Erectile dysfunction assessed by a single question during a self paced, computer-assisted self-interview. These data are nationally representative of the noninstitutionalized adult male population in the US. RESULTS: The overall prevalence of erectile dysfunction in men aged >/=20 years was 18.4% (95% confidence interval [CI], 16.2-20.7), suggesting that erectile dysfunction affects 18 million men (95% CI, 16-20) in the US. The prevalence of erectile dysfunction was highly positively related to age but was also particularly high among men with one or more cardiovascular risk factors, men with hypertension, and men with a history of cardiovascular disease, even after age adjustment. Among men with diabetes, the crude prevalence of erectile dysfunction was 51.3% (95% CI, 41.9-60.7). In multivariable analyses, erectile dysfunction was significantly and independently associated with diabetes, lower attained education, and lack of physical activity. CONCLUSIONS: The high prevalence of erectile dysfunction among men with diabetes and hypertension suggests that screening for erectile dysfunction in these patients may be warranted. Physical activity and other measures for the prevention of cardiovascular disease and diabetes may prevent decrease in erectile function. PMID- 17275457 TI - Resuscitation in the hospital: circadian variation of cardiopulmonary arrest. AB - PURPOSE: Over 25 reports have found outpatient frequency of sudden cardiac death peaks between 6 am and noon; few studies, with inconsistent results, have examined circadian variation of death in hospitalized patients. This study assesses circadian variation in cardiopulmonary arrest of in-hospital patients across patient, hospital, and event variables and its effect on survival to discharge. METHODS: A retrospective, single institution registry included all admissions to the Medical Center of Central Georgia in which resuscitation was attempted between January 1987 and December 2000. The registry included 4692 admissions; only the first attempt was reported. Analyses of 1-, 2-, 4-, and 8 hour intervals were performed; 1- and 4-hour intervals are presented. RESULTS: Significant circadian variation was found at 1 hour (P=.01), but not at 4-hour intervals. Significant circadian variation was found for initial rhythms that were perfusing (P=.03) and asystole (P=.01). A significantly higher percentage of unwitnessed events were found as asystole during the overnight hours (P=.002). Using simple logistic regression, time in 4-hour intervals and rhythm were each significantly related to patient survival until hospital discharge (P=.003 and P <.0001). In multivariate analysis, only rhythm remained significant. CONCLUSIONS: Circadian variation of cardiopulmonary arrest in this hospital has several temporal versions and is related to survival. Late night variation in witnessed events and rhythm suggests a delay between onset of clinical death and discovery, which contributes to poorer outcomes. PMID- 17275458 TI - The association of methamphetamine use and cardiomyopathy in young patients. AB - PURPOSE: Methamphetamine is the most widespread illegally used stimulant in the United States. Previously published case reports and series suggest a potential association between methamphetamine exposure and cardiomyopathy. The objective of this study is to demonstrate an association between methamphetamine use and cardiomyopathy. SUBJECT AND METHODS: Case-control study based on chart review of discharges from a tertiary care medical center from January 2001 to June 2004. Patients were < or =45 years old. Cases included patients with a discharge diagnosis of either cardiomyopathy or heart failure. Controls included hospitalized patients who had an echocardiographic assessment of left ventricular function with ejection fraction > or =55% and no wall motion abnormalities. RESULTS: One hundred and seven cases and 114 controls were identified. Both groups had similar gender distribution, length of hospital stay, rates of health insurance, prevalence of coronary artery disease, diabetes mellitus, hypertension, cigarette smoking, alcohol abuse, and marijuana and cocaine use. Cases were older than controls (mean age: 38 vs 35 years; P=.008), had higher body mass index (BMI) (mean BMI: 37 vs 30 kg/m2; P<.001), and higher prevalence of renal failure (13% vs 4.4%; P=.03). Methamphetamine users had a 3.7-fold increased odds ratio [95% confidence interval, 1.8-7.8] for cardiomyopathy, adjusting for age, body mass index, and renal failure. CONCLUSIONS: Methamphetamine use was associated with cardiomyopathy in young patients. PMID- 17275459 TI - Frequent needle exchange use and HIV incidence in Vancouver, Canada. AB - PURPOSE: Opposition to needle exchange programs has been fueled by a Vancouver study showing an association between frequent program use and elevated rates of human immunodeficiency virus (HIV) infection among injection drug users. METHODS: We evaluated possible explanations for the observed association between elevated HIV rates and frequent needle exchange attendance using a prospective observational cohort study of injection drug users in Vancouver, BC, Canada. HIV incidence rates were examined using stratified Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: Between May 1996 and December 2004, 1035 individuals were recruited. At 48 months after recruitment, the cumulative HIV incidence rate was 18.1% among those reporting daily needle exchange use at baseline, compared with 10.7% among those who did not report this behavior (P <.001). However, comparing HIV incidence among daily versus nondaily exchange users, while stratifying the cohort into those who did (23.2% vs 16.8%; P=.157) and did not (11.4% vs 9.0%; P=.232) report daily cocaine injection at baseline, the association between daily exchange use and HIV incidence was no longer significant. In an adjusted Cox model, daily exchange use was not associated with the time to HIV seroconversion (relative hazard=1.41 [95% confidence interval, 0.95-2.09]). CONCLUSIONS: Differential HIV incidence rates between frequent and nonfrequent needle exchange attendees can be explained by the higher risk profile of daily attendees. Causal factors, including the high rates of cocaine injection and other local injection drug user characteristics, explain the Vancouver HIV outbreak. PMID- 17275460 TI - Risk of mortality with vitamin E supplements: the Cache County study. AB - PURPOSE: A recent meta-analysis reported increased mortality in clinical trial participants randomized to high-dose vitamin E. We sought to determine whether these mortality risks with vitamin E reflect adverse consequences of its use in the presence of cardiovascular disease. METHODS: In a defined population aged 65 years or older, baseline interviews captured self- or proxy-reported history of cardiovascular illness. A medicine cabinet inventory verified nutritional supplement and medication use. Three sources identified subsequent deaths. Cox proportional hazards methods examined the association between vitamin E use and mortality. RESULTS: After adjustment for age and sex, there was no association in this population between vitamin E use and mortality (adjusted hazard ratio [aHR] 0.93; 95% confidence interval [CI], 0.74-1.15). Predictably, deaths were more frequent with a history of diabetes, stroke, coronary artery bypass graft surgery, or myocardial infarction, and with the use of warfarin, nitrates, or diuretics. None of these conditions or treatments altered the null main effect with vitamin E, but mortality was increased in vitamin E users who had a history of stroke (aHR 3.64; CI, 1.73-7.68), coronary bypass graft surgery (aHR 4.40; CI, 2.83-6.83), or myocardial infarction (aHR 1.95; CI, 1.29-2.95) and, independently, in those taking nitrates (aHR 3.95; CI, 2.04-7.65), warfarin (aHR 3.71; CI, 2.22-6.21), or diuretics (aHR 1.83; CI, 1.35-2.49). Although not definitive, a consistent trend toward reduced mortality was seen in vitamin E users without these conditions or treatments. CONCLUSIONS: In this population based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without. PMID- 17275461 TI - Impact of perioperative cardiac assessment guidelines on management of orthopedic surgery patients. AB - PURPOSE: The study assessed whether the American College of Cardiology/American Heart Association (ACC/AHA) preoperative cardiac assessment guidelines impact patient management and predict major cardiac events in patients undergoing orthopedic surgery. SUBJECTS AND METHODS: We conducted a retrospective review of 338 consecutive orthopedic preoperative evaluations performed by internal medicine consultants. Major cardiac events were defined as myocardial infarction, congestive heart failure, and sudden cardiac death. RESULTS: Major cardiac events occurred in 5.7% of patients. Patients with minor or absent ACC/AHA clinical risk predictors were less likely to have major cardiac events (P = .007). More than half (51%) of patients meeting ACC/AHA indications for noninvasive cardiac tests did not receive them. However, most (69%) major cardiac events occurred in patients not meeting criteria for cardiac testing. Abnormal noninvasive cardiac testing results did not alter medication recommendations and only resulted in coronary revascularization in 0.6% of patients. Only 3% of patients with abnormal noninvasive cardiac testing results had major cardiac events. Patients with abnormal cardiac test results were more likely to have recommendations for perioperative beta-blockade (P <.01). Patients aged more than 70 years (odds ratio 5.0; 95% confidence interval, 1.32-19.28) and patients undergoing hip surgery (odds ratio 7.5, 95% confidence interval, 1.02-54.55) were more likely to have major cardiac events. Major cardiac events occurred in 12% of urgent and 4% of elective procedures (P = .009). CONCLUSIONS: The ACC/AHA guidelines accurately predict cardiac risk in orthopedic surgery. Abnormal noninvasive cardiac test results rarely affected preoperative recommendations, but improved compliance with beta-blocker therapy. Advanced age, urgent procedures, and hip surgery were associated with increased risk of major cardiac events. PMID- 17275462 TI - The value of percutaneous coronary intervention in aortic valve stenosis with coronary artery disease. AB - OBJECTIVES: The study determines whether treatment of coronary disease by percutaneous coronary intervention (PCI) in the presence of severe aortic stenosis (AS) is feasible and defines which patients might benefit most. BACKGROUND: Severe symptomatic AS is considered a class I indication for aortic valve replacement (AVR). Many patients with AS have concomitant coronary artery disease (CAD), and the true reason for symptoms is often unclear. It is common practice to combine AVR with coronary artery bypass grafting. However, in some cases PCI alone might improve symptoms and allow surgery to be deferred. METHODS: We analyzed 38 consecutive patients who underwent PCI for CAD in the presence of significant AS between 1989 and 2004. Data included demographic factors, clinical features, angiographic, and echocardiographic information. Events during follow up included PCI complications, improvement post-PCI, AVR, and death. Statistical analysis was used to assess the impact of PCI on outcome and survival. RESULTS: The mean age of the study group was 71 +/- 9.3 years, and the mean aortic valve area was 0.84 +/- 0.28 (0.4-1.2) cm2. Reasons for choosing PCI over surgery were patients' preference, high surgical risk, and cardiologist recommendation. Thirty five patients (92.1%) reported symptomatic improvement after PCI, and no major PCI-related complications were recorded. Significant predictors for long-term event-free survival were good functional class (P = .006) and single-vessel coronary disease (P = .017). CONCLUSION: PCI in patients with severe AS and significant CAD is safe, offers relief of symptoms in most cases, and has good long-term outcome in a subset of patients who have mild CAD and good functional class. This therapeutic approach should be considered in such patients and in those with high surgical risk. PMID- 17275463 TI - Internal medicine department chairs: where they come from, why they leave, where they go. PMID- 17275464 TI - Transplantation proceedings in the second era: an organ undergoing evolution. PMID- 17275465 TI - Organ donation in the Basque country: 18 years experience. AB - PURPOSE: We reviewed of the trends in organ donation within a coordinated transplant program over the last 18 years. METHODS: Two thousand three hundred and fifty five potential donors (PD) were evaluated in 18 years including 1282 who were effective donors (EDs) and the 4081 harvested organs. A retrospective analysis of various parameters was performed comparing four different periods: 1981 to 1986 (P0); 1987 to 1992 (P1); 1993 to 1998 (P2); and 1999 to 2004 (P3). RESULTS: The potential donor detection rate (PD/PMP) increased from 18 in P0 to 47 in P3. The ED rate (ED/PMP) was 10 in P0 and 47 in P3. Organs donated ED evolved from 2.8 in P1 to 3.3 in P3. Mean donor age increased: 32 years in P1 and 53 in P3. ED/PD rate did not vary significantly in the three periods: P1, 54%; P2, 53%; and P3, 55%. There was a change in the main causes of death among our EDs: 54% head trauma, 36% stroke, and 16% other causes in P1 versus 30% head trauma and 64% stroke in P3. Failed donations due to medical contraindications were in P1 17% and in P3; whereas failed donation due to donor management problems and family denials to donation, both dropped: P1 16%; P3 10% and P1 13%; P3 7%, respectively. CONCLUSIONS: The ED rate increased almost fivefold since 1981 to 1986. We think that this was the result of a better detection since the beginning of our program. Failed donation due to medical exclusion criteria along with the mean donor age of our donors increased, but we noticed a significant drop in family denials and exclusions secondary to donor management problems. Our donor profile has changed considerably during 18 years: an increase of more than 20 years in the mean donor age along with an increase of more than 28% among strokes as the cause of death, leading to more failed donations secondary to medical exclusion criteria. PMID- 17275466 TI - Reliability of computed tomographic angiography in the diagnosis of brain death. AB - OBJECTIVE: This study examined the validity of cerebral computed tomographic (CT) angiography in the diagnosis of brain death (BD) compared with conventional cerebral angiography. METHODS: This prospective, monocentric study was performed over a 24-month period and included 43 patients, at least 18 years of age, with clinical criteria of BD. All patients underwent cerebral CT angiography and then cerebral angiography. To confirm BD, the CT scan had to show the absence of perfusion of A2 anterior cerebral artery segments (A2-ACA), M4 middle cerebral artery segments (M4-MCA), P2 posterior cerebral artery segments (P2-PCA), basilar artery, internal cerebral veins, and finally the great cerebral vein. Cerebral angiography showed cerebral blood flow arrest at the level of the foramen magnum for posterior circulation and carotid siphon for anterior circulation. RESULTS: For 30 patients, BD was confirmed by both examinations. For 13 patients, cerebral angiography confirmed BD, whereas CT angiography still showed cerebral perfusion; the divergence rate was 30.2%. CONCLUSIONS: CT angiography seems to be a promising exam to confirm BD. However, the divergence with cerebral angiography is significant mainly concerning A2-ACA, which are proximal. It may be possible to only use the absence of opacification of M4-MCA, P2-PCA, basilar artery, and venous blood return to remain in conformity with the French law. In all cases, the international medical community should obtain a consensus for the interpretation of CT angiography to use it extensively as a complementary exam for BD. PMID- 17275468 TI - Laparoscopic donor nephrectomy: effects of learning curve on surgical outcomes. AB - Our objective was to determine the effect of an experienced laparoscopic surgeon's learning curve with laparoscopic donor nephrectomy (LDN) on patient outcome and graft function. MATERIALS AND METHODS: Retrospective review of the medical records of the initial 73 consecutive LDN patients and corresponding transplant recipients was performed. All of the LDN were performed by a single, experienced laparoscopic surgeon (C.P.S.). The method of LDN was slightly different between the groups. RESULTS: Patients were divided into early and late groups with 37 and 36 patients, respectively. There was no statistically significant difference in mean estimated blood loss (245 +/- 671.2 vs 84.7 +/- 63.9 mL), warm ischemia time (159.7 +/- 66.3 vs 150.8 +/- 63.0 seconds), postoperative creatinine levels (1.34 +/- 0.24 vs 1.29 +/- 0.26 mg/dL,), recipient mean creatinine level at 1 month (1.57 +/- .98 vs 1.53 +/- 0.46 mg/dL), and hospital stay (2.49 +/- 0.87 vs 2.47 +/- 0.56 days) between the early and late groups. However, the difference in mean operative time between early and late groups was statistically significant (255.2 +/- 42.4 vs. 209.1 +/- 30.8 minutes, P < .05). In addition, there were 8 (21.6%) vs 4 (11.1%) instances of slow graft function and 3 (8.1%) vs 0 instances of delayed graft function among the recipients in early group versus the late group. There were four (10.8%) vs two (5.6%) minor complications among donors of the early and late groups, respectively. CONCLUSION: There is a significant decrease in operating time and incidence of delayed graft function following the first 37 patients who underwent LDN by an experienced laparoscopist. Improvement in operative technique decreased operative time and improved perioperative graft function as evidenced by decreased slow graft function and delayed graft function in the late group. PMID- 17275467 TI - Systemic and myocardial oxygen transport responses to brain death in pigs. AB - BACKGROUND: Brain death is associated with profound disturbances of systemic and myocardial oxygen transport, but little is known regarding the acute response of systemic oxygen consumption (VO(2)). METHODS: Brain death was induced in 6 pigs (30.6 +/- 3.0 kg) by balloon inflation into the cranial cavity. VO(2) was continuously measured by respiratory mass spectrometry. Blood pressures and gases were measured from the aorta, superior vena cava, and coronary sinus, with arterial epinephrine and norepinephrine, prior to brain death, at 1, 10, and 90 minutes after brain death. Cardiac output (CO), systemic vascular resistance (SVR), oxygen delivery (DO(2)), oxygen extraction (EO(2)), and myocardial oxygen (mEO(2)) and lactate extractions (mE(1ac)) were calculated. Left ventricular contractility was assessed by micromanometer tipped catheters. RESULTS: VO(2) increased from 4.8 +/- 0.9 to 6.3 +/- 0.9 mL/min/kg 1 minute after brain death (P < .001), and subsequently decreased to below baseline at 90 minutes (P < .001). Left ventricular contractility, CO, and DO(2) increased 1 minute after brain death (P < .001), followed by a rapid decrease to baseline within 10 minutes (P < .001). SVR and EO(2) decreased after brain death (P < .01) and remained low. Lactate remained unchanged. mE(1ac) decreased after brain death despite a decrease in mEO(2) (P < .01), and returned to baseline at 90 minutes. CONCLUSIONS: The initial surge in VO(2) after brain death is offset by the greater increase in DO(2), thus tissue perfusion remains adequate. The lower than baseline VO(2) and SVR at the end of the study period may indicate general metabolic and hemodynamic compromise. The information regarding the profound metabolic alterations imposed by brain death may have implications for management of brain death donors. PMID- 17275469 TI - Ten years of laparoscopic living donor nephrectomy: retrospect and prospect from the nephrologist's point of view. AB - The laparoscopic living kidney donor nephrectomy introduced in 1995 has become an accepted method of kidney harvest for transplantation. The method has proven its usefulness as well as its superiority compared to open donor nephrectomy. Based on the results of a decade, an overview from a nephrologist's point of view is presented here in; a view that is known to be quite different from (and sometimes contrary to) the surgeon's approach. While urologists and surgeons focus more on the technique and complication rates, the nephrologist tends to estimate the new procedure with regard to his dialysis patients' outcomes (ie, whether it will result in an increased number of kidney transplantations in the long term). The latter aspect has to be the benchmark in the estimation of the effects of this procedure; it is the ultimate goal of every surgery in kidney transplantation. The 10-year results are more than encouraging, but nevertheless it will take at least one more decade for a valid evaluation. PMID- 17275470 TI - Early coronary calcification in children and young adults with end-stage renal disease. AB - Cardiovascular disease is a major cause of morbidity and mortality in children and young adults with end-stage renal disease. In our study, we retrospectively analyzed the records of 11 patients who had undergone electron beam computerized tomography in our dialysis unit. Our patients, aged 11 to 24 years (median, 19.3 years) were on dialysis or had functioning grafts. Coronary calcification was observed in seven patients (64%) with a mean calcium score of 273.8 +/- 708 (range 0.8 to 1864) in our study population. We compared clinical characteristics like age, gender, duration of end-stage renal disease, time on hemodialysis, body mass index, and blood pressures between the patients with calcifications (group I) and those with out calcification (group II). We also compared the laboratory data including daily calcium and calcitriol intake, lipid profile, serum calcium and phosphorus levels, calcium/phosphorus products, and serum parathyroid hormone levels in the both groups. The mean daily dose of total calcium, triglyceride level, and calcium/phosphorus products were higher in the calcification group though not statistically significant. The mean daily dose of calcitriol was significantly higher in patients with calcification. Using Spearman multivariate correlation, we found a correlation between the coronary calcium scores and mean daily doses of total calcium and calcitriol (r = .750, P =.008 and r = .869, P = .001, respectively). We conclude that coronary calcification, which is a proven predictor of cardiovascular disease, begins at a very early age and that daily doses of elemental calcium and calcitriol seem to be important factors in our study population. PMID- 17275471 TI - Possible influence of vitamin D receptor gene polymorphisms on recombinant human erythropoietin requirements in dialysis patients. AB - BACKGROUND: Vitamin D receptor (VDR) gene polymorphisms have been widely studied, especially to analyze their effects on calcium-phosphorus metabolism and secondary hyperparathyroidism in patients on dialysis. In this study, we sought to investigate the possible effects of these polymorphisms on the anemia of renal failure and recombinant human erythropoietin (rHuEPO) responses among patients receiving hemodialysis. METHODS: One hundred twenty-eight patients (52 females/76 males) underwent genotyping for the insertion/deletion Bsml (B-->b, restriction site, exon VIII-->IX) and Tagl (T-->t, 352 exon IX) VDR gene polymorphisms. The mean value of the last 6 months' monthly evaluated laboratory values (C-reactive protein, hemoglobin, iron indices, PTH, and albumin) and clinical findings (rHuEPO requirement, cumulative iron supplementation doses, and body weight) were analyzed retrospectively excluding patients with chronic inflammation, hemolytic anemia, or active blood loss such as gastrointestinal bleeding. RESULTS: Mean age and dialysis durations were 41.5 +/- 11.8 years and 91.8 +/- 45.3 months, respectively. Polymorphism percentages were as follows: Bsml; BB/Bb/bb: 32.2/63.6/4.2 and Tagl; TT/Tt/tt: 40.5/55.4/4.1%, respectively. BB variant of Bsml gene was related to lower rHuEPO needs (P < .05) and also higher hemoglobin levels (P < .005) when compared with the Bb/bb variant. Considering Tagl variants, transferrin saturation levels were lower (P < .03) among patients with the Tt/tt variant, but there was no other significant difference in the mean values of other data between TT and Tt/tt variants. CONCLUSION: The BB variant of Bsml was related to decreased rHuEPO requirements to achieve higher hemoglobin levels among maintenance hemodialysis patients without chronic inflammation. PMID- 17275472 TI - Renal transplantation in dialysis patients with the history of coronary artery bypass grafting and cardiac valve replacement. AB - Death with a functioning kidney is the most frequent cause of graft failure. Cardiovascular disease is the most frequent cause of death after renal transplantation. Therefore, prior to grafting, it is mandatory to diagnose and treat coronary artery disease and heart valve impairment. Transplantation is the best option for renal replacement therapy as far as the quality of life and life expectancy are concerned, although patients with such comorbidities may experience a higher short-term mortality risk. The objective for this study was to analyze both short- and long-term results of patients after coronary artery bypass grafting (CABG) or cardiac valve replacement (CVR). The cardiac surgery recipient group (CSR) included 16 patients (15 men, 1 woman) aged from 44 to 73 (mean 54.9 +/- 7.8) years. CABG was performed in 13/16 patients, and CVR in 3/16. The rest of our patients were treated as a comparative noncardiac surgery recipient (non-CSR) group. It consisted of 422 patients (264 men, 158 women) aged from 14 to 68 years (mean 43.2 +/- 12.9). The comparison revealed that graft function estimated at 1 year after transplantation was not different: serum creatinine concentrations of 1.7 +/- 0.2 and 1.6 +/- 0.5 mg/dL in CSR and non CSR, respectively. One-year patient survival in the CVR group of 93.8% was slightly worse than that in the non-CSR group (97.9%), but death-censored 1-year graft survivals were comparable in both groups (93.8% vs 92%). Urinary tract and cytomegalovirus infections were the most common complications in the CSR group. One patient lost his graft in month 3(rd) due to many serious infectious complications. One patient died at the end of 12 months as a result of a cardiovascular event (1/16). Our single-center results confirm that transplantation in patients after CABG or CVR is a safe procedure; therefore, such patients should be referred into the waiting list. PMID- 17275473 TI - Translation, cultural adaptation, initial reliability, and validation of the Kidney Disease and Quality of Life-Short Form (KDQOL-SF 1.3) in Turkey. AB - Health-related quality of life (HRQoL) is an important factor that can interfere with treatment outcomes. The aim of the present study was cultural adaptation, validation, and translation of the Kidney Disease Quality of Life-Short Form (KDQoL-SF 1.3) questionnaire into Turkish for the Turkish population. The KDQOL SF was translated into Turkish and back-translated into English. Patient difficulties in understanding the questionnaire were evaluated and solved by a panel of experts. Measurement properties such as reliability and validity were determined by applying the questionnaire to 82 patients on dialysis, who were randomly selected from the dialysis units of 3 educational and research hospitals in Istanbul: 65% were females; mean patient age was 51 +/- 12 years. The most common primary causes of renal failure were glomerulonephritis (47%), hypertension (31%), and diabetes (7%). The median time on dialysis among the patients was 3 years. Test and retest methods were used for reliability. The total test-retest reliability Cronbach alpha coefficient of the Turkish KDQOL-SF questionnaire was 0.84 to 0.91. These coefficients were statistically significant (P < .05) for 19 dimensions of the KDQOL-SF that ranged from 0.75 to 0.91. The Cronbach alpha coefficient was higher than 0.80 for most components. To evaluate its construct validity, the KDQOL-SF was compared with the Turkish version of the 15D, an instrument for global assessment that contains 15 items divided into 5 dimensions. The scores range from 0 to 1 (0 = worse health status, 1 = better health status). Significant correlations were observed between the scores of the similar domains of the 15D and the KDQOL-SF. The best correlations were observed between physical functioning (KDQOL-SF) and mobility (15D; r = -.810) and between emotional well-being of (KDQOL-SF), and with the mental functions of 15D; (r = .784), sexual function (KDQOL-SF) and sexual activity (15D; r = -.781), and patient satisfaction and distress (r = -.801). These findings support the construct validity of the new Turkish adapted KDQOL-SF. This study is reporting the complete process of translation and validation of the KDQOL-SF in the literature. These results demonstrate the high reliability and validity of this questionnaire for Turkish patients on dialysis. PMID- 17275474 TI - Assessment of differences in HLA-A, -B, and -DRB1 allele mismatches among African American and non-African-American recipients of deceased kidney transplants. AB - Among recipients of deceased donor kidney transplants, African-Americans experience a more rapid rate of kidney allograft loss than non-African-Americans. The purpose of this study was to characterize and quantify the HLA-A, -B, and DRB1 allele mismatches and amino acid substitutions at antigen recognition sites among African-American and non-African-American recipients of deceased donor kidney transplants matched at the antigen level. In recipients with zero HLA antigen mismatches, the degree of one or two HLA allele mismatches for both racial groups combined was 47%, 29%, and 11% at HLA-DRB1, HLA-B, and HLA-A, respectively. There was a greater number of allele mismatches in African Americans than non-African-Americans at HLA-A (P < .0001), -B (P = .096), and DRB1 loci (P < .0001). For both racial groups, the HLA allele mismatches were predominantly at A2 for HLA-A; B35 and B44 for HLA-B; but multiple specificities for HLA-DRB1. The observed amino acid mismatches were concentrated at a few functional positions in the antigen binding site of HLA-A and -B and -DRB1 molecules. Future studies are ongoing to assess the impact of these HLA mismatches on kidney allograft loss. PMID- 17275475 TI - Histoblood groups other than HLA in organ transplantation. AB - Immunological matching of a living related donor and recipient of an allograft is precise, but for cadaver organs matching is controversial, including at least detection of specific sensitization in the recipient against the donor, especially for HLA-DR. With the publication of some cases of ABO histoblood group incompatible transplantations with favorable outcomes, transplantation immunologists now focus on many of the 29 International Society of Blood Transfusion-approved histoblood group systems. So far, research lags behind knowledge about which system occurs in which organ, but modern molecular biology tests, like basic local alignment search tools (BLAST) and the recent inclusion of some systems into the CD classification, make possible the tracking of some histoblood group epitopes to specific tissue components. We have conducted such a search. With respect to tissue distribution, mRNA transcripts, and expressed sequence tags (EST), we observed a huge variety of distribution patterns. The total number of EST in the embryo pool was 752,991 and in the adult pool 1,227,835. Representative results were described for umbilical cord, bone marrow, peripheral stem cells, the nervous system, and the embryo. The ABO histoblood group systems maintain high priority for matching, because of the occurrence of naturally occurring anti-A/B antibodies. Substantial progress has been made in monitoring their levels and immunoglobulin isotypes in recipients, which, beyond hemagglutination, can now be quantitated using ELISA or cytofluorometry. A picture of ever-improving compatibility matching in solid organ and stem cell transplantation beyond mere HLA typing is the consequence. PMID- 17275476 TI - One year results of preoperative single bolus ATG-Fresenius induction therapy in sensitized renal transplant recipients. AB - Sensitization in kidney transplantation is associated with more acute rejections, inferior graft survival, and an increase in delayed graft function. This study was designed to evaluate the efficacy and safety of preoperative single bolus antithymocyte globulin (ATG) induction therapy in sensitized renal transplant recipients. METHODS: Fifty-six cadaveric donor kidney transplant recipients were divided into two groups: Group I (nonsensitized group, n = 30) and group II (sensitized group, PRA>10%, n = 26). ATG was given as a single preoperative bolus induction therapy to group II (ATG IV; 9 mg/kg). The group I patients were treated with mycophenolate mofetil preoperatively as induction therapy. The basic immunosuppressive regimen included tacrolimus (FK-506) or cyclosporine, mycophenolate mofetil, and prednisolone. After hospital discharge, patients were followed on a routine outpatient basis for 12 months. RESULTS: Acute rejection episodes (ARE) occurred in 20% (6/30) of group I and 15.38% (4/26) of group II patients (P = NS). Infections occurred in eight patients (26.7%) as 11 episodes (36.7%), averaging 1.4 episodes per infected patient in group 1, and 6 patients (23.1%) for a total of 10 episodes (38.5%), averaging 1.7 episodes per infected patient, in group II (P = NS). Occurrence of side effects and hospital stay were almost comparable in the two groups. No delayed graft function was observed in either group. The 12-month actuarial patient and graft survival were 100% in Group I and II. CONCLUSION: A preoperative single bolus ATG induction therapy was an effective and safe therapeutic measure, yielding an acceptable acute rejection rate in presensitized renal transplant recipients. PMID- 17275477 TI - DNA fragmentation in acute and chronic rejection after renal transplantation. AB - Acute and chronic rejections are important denominators for the long-term function of renal grafts. One important indicator of cell damage is enzymatic DNA fragmentation. To investigate possible mechanisms, the rate of DNA fragmentation (TUNEL staining), the expression of tissue transglutaminase II (a marker of advanced DNA damage), and 8-hydroxy-2'-deoxyguanosine (8-OhdG), an indicator of oxidative injury of nucleic acids, were studied by immunohistochemistry. Semithin sections of renal biopsies revealed 23 patients to show acute interstitial rejections (Banff 97 IA, IB); eight patients, acute vascular rejection (Banff 97 IIA, IIB); and 20 patients, chronic allograft nephropathy (Banff 97 I to III). Correlations were calculated between apoptotic cells and serum creatinine at the time of biopsy and after 6 months. In acute rejection, the proximal tubular cells were apoptotic, particularly in regions with mononuclear infiltrates. In consecutive sections, these apoptotic tubular cells also showed damage by reactive oxygen species (positive 8-OhdG staining). Patients with acute interstitial rejection revealed the highest number of tubular DNA fragmentation (14.9 +/- 10.3) versus chronic allograft nephropathy (9.2 +/- 5.6) as TUNEL positive cells per 80,000 micro m(2) (P < .05). Patients with acute vascular rejection showed a low degree of tubular apoptosis (6.8 +/- 5.1). There was no significant difference in glomerular DNA fragmentation between acute interstitial and chronic rejections: acute interstitial rejection = 7.1 +/- 5.9 versus chronic allograft nephropathy=6.1 +/- 3.9 TUNEL-positive cells per 80,000 micro m(2). There was a significant negative correlation between the degree of tubular (P < .01) and glomerular (P < .05) apoptosis and the serum creatinine at the time of biopsy as well as after 6 months in all patients irrespective of the Banff class. However, there was heterogeneity in the correlation between renal function and the degree of apoptosis in the glomerular and tubular compartments in the various Banff classes. A positive correlation (P < .01) was observed between the degree of tubular apoptosis and serum creatinine at 6 months after biopsy among patients with acute vascular rejection (Banff 97 IIA, IIB). The present data revealed a high degree of tubular DNA fragmentation associated with oxidative stress in acute interstitial rejection. Nevertheless, apoptosis did not generally negatively influence future renal function and may be important to clear proliferating cells. Apoptosis may also play a different pathophysiological role depending on the type of rejection. PMID- 17275478 TI - Combination of angiotensin-converting enzyme and methylenetetrahydrofolate reductase gene polymorphisms as determinant risk factors for chronic allograft dysfunction. AB - OBJECTIVE: The aim of this study was to investigate the frequency of gene angiotensin-converting enzyme insertion/deletion (ACE I/D) and methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) variants, as well as to evaluate the plasma homocysteine concentrations in 217 patients who underwent renal transplantation at least 12 months prior to define risk factors for chronic allograft dysfunction. METHODS: The presence of the polymorphism ACE deletion was assessed by polymerase chain reaction (PCR) analysis. MTHFR polymorphisms were determined by PCR and restriction fragment length polymorphism (RFPL) techniques. The restriction enzymes were Hinf I and Mbo II for MTHFR variants C677T and A1298C, respectively. Plasma homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry (LS-MS/MS). RESULTS: Hyperhomocysteinemias were more common in patients with chronic allograft dysfunction (P = .004). No statistically significant differences were observed between the allelic and genotypic distributions of MTHFR and ACE polymorphisms. An effective risk factor was found when the polymorphisms of the ACE and MTHFR genes and hyperhomocysteinemia were associated (odds ratio 2.51; 95% confidence interval 1.19-5.28). In conclusion, our study identified that the presence of hyperhomocysteinemia in combination with unfavorable genotypes contributes to an increased risk for development of chronic allograft dysfunction. PMID- 17275479 TI - Expression of neuropilin-1 in kidney graft biopsies: what is the significance? AB - OBJECTIVE: Recent work has suggested that neuropilin-1 (NRP-1) is a surface marker of regulatory T cells (Treg). However, no further relative evidence has been provided to confirm this finding. Since Treg should decline during rejection, the expression of NRP-1 on lymphocytes should decline in a rejected graft. To test this proposal, we examined NRP-1 expression in kidney graft biopsies. MATERIALS AND METHODS: Tissue samples were obtained from 20 kidney graft biopsies with pathologically confirmed acute rejection and from 10 without rejections. We performed immunohistochemistry assays using an anti-NRP-1 monoclonal antibody. The positive cells were counted and the ratios among lymphocytes analyzed. RESULTS: Compared with samples from nonrejected graft biopsies (18.71 +/- 20.60), the number of positive cells among lymphocytes in the rejected samples showed a lower percentage (3.16 +/- 1.72; P < .05). CONCLUSIONS: NRP-1 has an important role in directing the growth of nervous synapses and immune synapses. We found in rejected grafts that the percentage of NRP-1 positive cells among lymphocytes decreased significantly. Therefore, NRP-1 may have a previously unrecognized role to predict the immune state of the graft as a potential marker for Treg. PMID- 17275480 TI - Prospective evaluation of BK virus DNAemia in renal transplant patients and their transplant outcome. AB - BACKGROUND: After renal transplantation, the prevalence of BK virus (BKV) viruria, viremia, and nephritis (BKVAN) has been estimated at 30%, 13%, and 8%, respectively. PATIENTS AND METHODS: The aim of this prospective study was to assess the occurrence of BKV DNAemia during the first year after renal transplantation and to determine the prevalence of BKVAN, in the absence of immunosuppression alteration, following positive BKV DNA. BKV DNAemia was assessed systematically in 104 renal transplant patients on postoperative days 60, 90, 135, 180, 270, and 360. RESULTS: Of the 104 patients, 7 (6.7%) presented with at least 1 episode of BKV DNAemia. Those with positive BKV DNAemia had a cumulative steroid dose administered from days 0 to 7 which was higher than those without BKV DNAemia (2.13 +/- 0.6 vs 1.6 +/- 0.4; P = .024). The first BKV DNAemia occurred at 170 (30-460) days posttransplantation. Of the 7 patients who experienced at least 1 BKV DNAemia, 3 had 1 occurrence, but the other 4 had repeated occurrences. These 4 patients developed overt BKVAN at 1 (2 cases) to 2 weeks (2 cases) after the first occurrence of BKV DNAemia. These 4 patients were withdrawn from mycophenolate mofetil, which was in all cases replaced by leflunomide. With a follow-up ranging from 14 to 24 months after the first episode of BKV DNAemia, patient and graft survivals were both 100%. Current serum creatinine ranges from 97 to 173 micro mol/L for those who had only 1 episode of BKV DNAemia, and from 144 to 240 micro mol/L for those who had overt BKVAN. CONCLUSION: Although BKV DNAemia is a rare event after renal transplantation, it is often associated with BKVAN, which may be treated successfully by the alleviation of immunosuppression and leflunomide therapies. PMID- 17275481 TI - Noninfectious gastrointestinal (GI) complications of mycophenolic acid therapy: a consequence of local GI toxicity? AB - Mycophenolic acid (MPA), a reversible inhibitor of inosine 5''-monophosphate dehydrogenase (IMPDH), selectively inhibits T- and B-cell proliferation. MPA exposure correlates inversely with the risk of acute rejection. Mycophenolate mofetil (CellCept; MMF) is an immediate-release formulation of MPA that is absorbed in the stomach and small intestine. Enteric-coated mycophenolate sodium (myfortic; EC-MPS) delays MPA release until the small intestine. There are some indications that EC-MPS may be associated with improved gastrointestinal (GI) toxicity. It is widely believed that systemic MPA exposure determines the extent of GI toxicity. However, intestinal cells absorb purines locally from the gut lumen via passive diffusion and a specific transport mechanism. It seems likely that local, rather than systemic, MPA exposure is responsible for GI events. Acyl MPAG, a toxic metabolite of MPA, may be produced by GI cells contributing to MPA related gut toxicity, suggesting that measures to alter the rate or location of MPA absorption could be beneficial. Lastly, the release of N-(2 hydroxyethyl)morpholine following deestification of MMF may have local irritative effects on gastric mucosal cells. Research which more closely focuses on the local gut pathobiology of MPA-containing drugs may provide a much clearer understanding of the dose-limiting toxicity of this drug class. PMID- 17275482 TI - Chronic allograft nephropathy score before sirolimus rescue predicts allograft function in renal transplant patients. AB - Chronic allograft nephropathy (CAN) is a major indication for initiation of sirolimus (SRL) in renal transplantation (TX) to prevent deterioration of renal function. We evaluated whether the CAN score at time of sirolimus rescue (SRL-R) predicts renal allograft function. CAN score is the sum of the following 4 categories: glomerulopathy (cg, 0-3), interstitial fibrosis (ci, 0-3), tubular atrophy (ct, 0-3), and vasculopathy (cv, 0-3). This is a retrospective cohort study of renal transplant recipients from July 2001 to March 2004. Immunosuppression consisted of preconditioning with rabbit anti-thymocyte globulin or alemtuzumab and maintenance with tacrolimus (TAC) monotherapy with spaced weaning, if applicable, SRL-R was achieved by conversion from TAC, or by addition to reduced doses of TAC. Ninety patients received SRL. Thirty-three of these patients met the inclusion criteria of the following: (1) receipt of SRL for >6 months, and (2) follow-up of > or =6 months. There were 16 patients in the low-CAN (0-4) group and 17 patients in the high-CAN (>4) group. Cockcroft-Gault (C-G) glomerular filtration rate (GFR) was calculated at SRL-R and at 1, 3, 6, and 12 months. The DeltaGFR was significantly better in the low-CAN group at 1, 3, and 6 months. A trend toward an improved DeltaGFR was present at 12 months in the low-CAN group (P = .16). CAN scoring at the time of SRL-R predicts recovery of renal allograft function (as measured using DeltaGFR), and should be used in preference to biochemical markers (Cr and C-G GFR), which may not be reliable predictors. PMID- 17275483 TI - Four cases of sirolimus-associated interstitial pneumonitis: identification of risk factors. AB - Sirolimus-associated interstitial pneumonitis is a severe side effect of sirolimus therapy; fatal outcomes have been described. We report 4 patients with sirolimus-associated interstitial pneumonitis and review the literature for risk factors for the development of disease. Until June 2005, 48 patients received either de novo sirolimus treatment (n = 7) or were switched from a calcineurin inhibitor-containing regimen to a sirolimus-based protocol for various indications (n = 41). Compared with the 44 patients on sirolimus therapy with no evidence of a disorder, the 4 patients (8.3%) who developed suspected sirolimus associated interstitial pneumonitis showed no difference in gender, immunosuppressive therapy, days posttransplantation, comorbidity, or preexistent lung disease. Several points, however, are of interest. None of the de novo treated patients except 4 patients (9.8%) with late administration of sirolimus developed interstitial pneumonitis. The 4 patients with interstitial pneumonitis tended to be older (58.7 +/- 5.5 vs 46.9 +/- 1.7 years) and received higher sirolimus doses (3.5 +/- 0.5 vs 1.4 +/- 0.2 mg/d) with greater trough levels (15.4 +/- 2.9 vs 8.0 +/- 1.2 micro g/L) at the onset of symptoms. Most notably, all patients with interstitial pneumonitis had a loading dose at the start of therapy, and an increase in sirolimus dose (or trough level) within 3 weeks prior to the onset of symptoms. Additional potential risk factors identified from the literature include allograft dysfunction, hypervolemia, and male gender. With careful monitoring (or even exclusion from therapy) of patients at risk for the development of disease, we have had no case of sirolimus-associated interstitial pneumonitis since September 2004. PMID- 17275484 TI - Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable maintenance renal transplant patients: pooled results from three international, multicenter studies. AB - BACKGROUND: Mycophenolate mofetil (MMF) is effective in renal transplant patients but concerns remain over its gastrointestinal (GI) tolerability. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed with the intention of improving mycophenolic acid-related GI tolerability. METHODS: Data were pooled in a planned analysis of three subprotocols of the myfortic Prospective Multicenter Study (myPROMS). In a 6-month study, efficacy and safety of converting stable renal transplant recipients from MMF to a bioequivalent dose of EC-MPS for mycophenolic acid exposure were evaluated. Treatment efficacy was recorded and graft function was assessed by measuring serum creatinine and estimating creatinine clearance. Adverse events (AEs) and infections were monitored and the incidence of EC-MPS dose changes was recorded. RESULTS: A total of 588 patients were recruited, 564 (96%) of whom completed the study. The rate of treatment failure (defined as biopsy-proven acute rejection, graft loss, or death) was 1.9%, with no episodes of graft loss and only one death reported during the study. Renal function remained stable throughout the trial. EC-MPS was well tolerated; the majority of AEs were mild or moderate in severity. Dose reductions or interruptions were required by 6.3% and 1.9% of patients, respectively. Gastrointestinal AEs occurred in 138 patients (23.5%). The rate of dose adjustment as a result of a GI AE was 2.2%. CONCLUSIONS: Equimolar conversion from MMF to EC-MPS in maintenance renal transplant patients was safe and maintained efficacy. PMID- 17275485 TI - Pharmacokinetics of neoral in stable renal transplant recipients with long-term diabetes mellitus. AB - Therapeutic drug monitoring (TDM) of Neoral has been studied widely and C2 monitoring has been shown to be superior to C0 monitoring in predicting outcomes. However, data are scarce in diabetic renal transplant recipients who may have gastroparesis. We studied 0 to 8 hour pharmacokinetic profiles (AUC(0-8h)) of Neoral on 3 consecutive days in 18 diabetic adults who had stable renal function for at least 6 months after transplantation and no overt symptoms of diabetic gastroparesis. All patients had diabetes mellitus (DM) for at least 5 years. Intrapatient variability of C2 levels was 28% (range, 6%-68%); it was < or =20% in 9 patients (50%) and >60% in 2 patients. Correlation coefficients between AUC(0-8h) and AUC(0-4h), between C2 and AUC(0-8h), and between C0 and AUC(0-8h) were 0.95, 0.86, and 0.77, respectively. Exposure phase (85% of AUC(0-8h)) was longer than 4 hours in all completed (48/54; 89%) profiles; it was longer than 6 hours in 20 profiles. C4 levels had good correlation with AUC(0-8h) (0.86) and low intrapatient variability (16% +/- 11%; range, 2%-39%). Thirteen of 18 patients (72%) had intrapatient variability of C4 < or = 20%. We conclude that the exposure phase of Neoral is prolonged more than 4 hours in adult renal transplant recipients with long-term diabetes, even in the absence of symptoms of gastroparesis. Because of very high intrapatient variability in this group of patients, C2 levels may not be reliable for TDM of Neoral despite high correlation with AUC(0-8h). C4 level may be a valid alternative for these patients. PMID- 17275486 TI - Immunoregulation of thymosin alpha 1 treatment of cytomegalovirus infection accompanied with acute respiratory distress syndrome after renal transplantation. AB - We are the first to report the use of thymosin alpha1 to treat cytomegalovirus infection accompanied with acute respiratory distress syndrome after renal transplantation. The patients were divided into the thymosin alpha1 group (Zadaxin group, n = 32) and the control group (n = 14). All patients received the same rescue therapy protocol. Suitable antiviral (ganciclovir, 5 mg/kg every 12 hours, intravenously), antibacterial, or antifungal treatment was given if needed. In addition, patients in the Zadaxin group received thymosin alpha1, (1.6 mg) subcutaneously every other day or every day. The rescue success rate was significantly higher in the Zadaxin than in the control group (78.1% vs 50.0%) while the death rate was greatly reduced (21.9% vs 50%). In the Zadaxin group, the CD4(+) lymphocyte level was significantly increased on day 14; so was the ratio of CD4(+) and CD8(+) T-lymphocyte subsets. In the survival group, CD4(+) and CD8(+) lymphocyte cell counts were significantly increased on days 7, 14, and 21 compared with admission. This study suggested that thymosin alpha1 significantly promoted CD4(+) and CD8(+) lymphocytes, repairing cellular immunity and successfully reinforcing resistance to cytomegalovirus disease. PMID- 17275487 TI - Complications of renal transplantation in patients with amyloidosis. AB - OBJECTIVE: Renal transplantation in patients with end-stage renal failure (ESRF) secondary to amyloidosis carries a high risk of postoperative complications. Preoperative investigations are crucial for a successful perioperative course. There are limited data studying the outcome of patients with amyloid nephropathy who undergo renal transplantation. Therefore, we undertook this retrospective review of our experience to highlight the difficulties. MATERIALS AND METHODS: Thirteen patients with AA amyloid-induced ESRF underwent cadaveric renal transplantation from 1985 to 2001 in the Irish transplant population. The perioperative course of these patients was compared to an age-matched control group of 142 nonamyloid patients who had cadaveric renal transplantation during the same time period. Both groups were followed annually for 5 years. RESULTS: The 1- and 5-year patient survival rates were 69% and 69% in the amyloid as compared with 97% and 87% for the control group. In the amyloid group, early death was primarily due to cardiac causes followed by complications of sepsis. Graft survival at 1 and 5 years was 56% and 56% in the amyloid group as compared with 87% and 59% in the control group (P = .0027). Four deaths with a functioning graft contributed to the early graft losses. CONCLUSION: Increased complications, especially cardiac, are noted post-renal transplantation among patients with renal amyloidosis. However, appropriate guideline, for the perioperative management of these patients has yet to be established. PMID- 17275488 TI - Successful kidney transplantation reduces hyperplastic parathyroid gland. AB - INTRODUCTION: In dialysis patients, the parathyroid glands (PTGs) may increase progressively, producing abnormal bone metabolism. Changes in PTG volume among patients with hyperplastic PTGs are not well known after kidney transplantation. This study investigated PTG volume by ultrasound (US). METHODS: US of PTG was performed immediately (US-0) and 12 months after (US-12) transplantation to identify glands in all recipients. We calculated the percentage reduction in PTG volume (R%PTG). We declared it significant when it was > or =35%. Bone biochemical markers and renal function were recorded sequentially. RESULTS: Among engrafted patients, parathyroid US-0 was performed in 47 and US-0 and US-12 in 36. Some visible gland was observed upon US-0 in 13 recipients, a group that showed higher pretransplantation parathyroid hormone (PTH) levels than the remaining 34 patients with no visible glands (627 +/- 360.0 vs 280 +/- 240.9 pg/mL; P < .05). Of 36 recipients with US-0 and US-12, the baseline study identified PTGs in 12 patients (p+ group), while the remaining 24 had no identified glands (p- group). In the p+ group, no PTG, at US-12 were visible in four patients, and a significant R%PTG was observed in three at this time, representing a reduction in gland volume after transplantation among 58.3% of p+ patients. There was a progressive reduction in PTH among both groups. Patients with glandular volume reduction displayed better renal function: serum creatinine 1.7 +/- .79 versus 2.9 +/- .74 mg/dL (P < .05). CONCLUSIONS: Transplantation reversed hyperparathyroidism and PTG volume among recipients who achieved nearly normal renal function. PMID- 17275489 TI - Perioperative erythropoietin efficacy in renal transplantation. AB - BACKGROUND: There is no consensus on the usage of erythropoietin in the immediate postoperative period to prevent anemia and delayed graft function. METHODS: A retrospective case note audit of renal transplants included hemoglobin (Hb) and serum creatinine (Scr) values preoperatively as well as at days 7, 14, 30, 60, and 90. Patients were categorized as those receiving erythropoietin during the first 6 months posttransplant (Epo+ve) and those not receiving any erythropoietin (Epo-ve). RESULTS: Hb decreased from 12.4 +/- 1.6 g/L preoperatively to 9.5 +/- 1.5 g/L at day 14 and then rose to 10.5 +/- 1.6 g/L at 1 month and 12.4 +/- 1.7 g/L at 3 months. There was no difference in absolute Hb values in three transplant groups. Scr decreased from 597.0 +/- 200.1 mmol/L preoperatively to 254.1 +/- 196.9 mmol/L at day 14 and continued to fall to 163.8 +/- 98.9 mmol/L at 1 month and 147.8 +/- 66.9 mmol/L at 3 months. There was no difference in absolute Hb values and delayed graft function in the three transplant groups. CONCLUSION: With respect to anemia and delayed graft function, the use of erythropoietin in the first 3 months had little impact. We suggest that such an expensive medication may be safely omitted in the immediate postoperative period. PMID- 17275490 TI - Lipid profile during azathioprine or mycophenolate mofetil combinations with cyclosporine and steroids. AB - BACKGROUND: Immunosuppressive therapy is the major cause of hyperlipidemia after renal transplantation. We sought to compare the effects of an azathioprine (AZA) combination (n = 26) with corticosteroid and cyclosporine (CyA; group 1) with a mycophenolate mofetil (MMF) combination (n = 71; group 2) in the first year following renal transplantation. METHODS: Ninety-seven renal transplant patients (71 men, 26 women; aged 34.7 +/- 13.1 years; renal transplantation duration, 44.9 +/- 12.9 months) underwent serum lipid profiles--total cholesterol, triglyceride, high-density lipoprotein (HDL); low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) at the initiation of as well as 3-month intervals after grafting for 1 year retrospectively. Serum creatinine for each patient was recorded at 12 months. We evaluated possible risk factors for hyperlipidemia. RESULTS: For all patients, the prevalence of hypercholesterolemia (>200 mg/dL) was 36.1% during the pretransplant period, 60.8% at month 3, 50.5% at month 6, and 38.1% at month 12 after renal transplantation. Total cholesterol and triglyceride levels significantly increased in both groups in the first year (P = .001 and P = .02, respectively). Three-month values for total cholesterol were higher in group 2 than group 1 (P = .001). No significant difference was observed between the groups with respect to total cholesterol and triglyceride levels (P > .05). In both groups, HDL, LDL, and VLDL levels did not change during the 12 month study (P > .05 for all). CONCLUSIONS: Independent of hyperlipidemia risk factors, serum total cholesterol and triglyceride levels tended to increase during CyA and steroid therapy among patients undergoing renal transplantation. Combination with MMF or AZA showed no advantage over one another regarding their effects on the lipid profile. PMID- 17275491 TI - Donor risk factors for renal graft thrombosis. AB - Graft thrombosis is one of the most devastating complications of transplantation. In obtaining consent prior to transplant, it is useful to share potential risk factors with the recipient. In order to do this, we explored the impact of different risk factors that could contribute to this complication. Using multivariate analysis we found that neither multiple vessels nor vascular injury had a bearing on the risk of graft thrombosis but atheroma did (P < .02). PMID- 17275492 TI - Saphenous vein interposition as a salvage technique for complex vascular situations during renal transplantation. AB - The shortage of donor organs for renal transplantation leads to the necessity of accepting organs with vascular disadvantages, such as venous difficulties (eg, shortness, disrupted vein after explantation) or arterial problems (eg, iatrogenic vascular accidents, arterial plaques, hemodynamically relevant polar arteries) and horseshoe kidneys. Consequently, such organs may not be considered for transplantation. Surgeons still have the ability to use such organs by saphenous vein interposition. This study focused on the frequency of vascular difficulties in 100 randomly selected kidney transplantations and their outcomes after arterial or venous saphenous vein interposition. PMID- 17275493 TI - Three-dimensional computed tomography for planning donor hepatectomy. AB - BACKGROUND: An accurate estimation of preoperative volumetric measurements of the donor liver is essential in living donor liver transplantation. METHODS: Three dimensional (3-D) computed tomography (CT) was applied to 56 living donors. 3-D images of the liver were constructed using the region-growing method and the volume of each sector was measured. RESULTS: The median volume ratios of the left liver, caudate lobe, right paramedian, and lateral sectors were 34%, 4%, 38%, and 25% of the total liver volume, respectively. The shape of the congestive area in the right paramedian sector was properly demonstrated by 3-D CT. The volume of the region corresponded to 32% of the right liver. The actual volume of the graft correlated well with the estimated graft volume (n = .86). CONCLUSIONS: The region-growing method was useful for graft selection and for determining the indication of middle hepatic vein reconstruction in right liver grafts. PMID- 17275494 TI - Safety of donor in adult-to-adult living donor liver transplantation using right lobe graft. AB - BACKGROUND: The growing gap between the number of patients awaiting liver transplantation and available organs has continued to be the primary issue facing the transplant community. To overcome the waiting list mortality, living donor liver transplantation has become an option, in which the greatest concern is the safety of the donor, especially in adult-to-adult living donor liver transplantation (A-A LDLT) using a right lobe liver graft. OBJECTIVE: We evaluated the safety of donors after right lobe liver donation for A-A LDLT performed in our center. METHODS: From January 2002 to March 2006, 26 patients underwent A-A LDLT using right lobe liver grafts in our center. Seven donors were men and 19 were women (range, 19-65 years; median age, 38 years). The right lobe liver grafts were obtained by transecting the liver on the right side of the middle hepatic vein without interrupting the vascular blood flow. The mean follow up time for these donors was 9 months. RESULTS: These donor residual liver volumes ranged from 30.5% to 60.3%. We did not experience any donor mortality. Two cases (7.69%) experienced major complications: intra-abdominal bleeding and portal vein thrombosis in one each and three (11.54%), minor ones: wound steatosis in two, and transient chyle leak in one. All donors were fully recovered and returned to their previous occupations. CONCLUSIONS: A-A LDLT using a right lobe liver graft has become a standard option. The donation of right lobe liver for A-A LDLT was a relatively safe procedure in our center. PMID- 17275495 TI - Multimodality therapy and liver transplantation in patients with cirrhosis and hepatocellular carcinoma: 6 years, single-center experience. AB - The treatment of patients with cirrhosis and hepatocellular carcinoma (HCC) has improved dramatically over the past 10 years. We conducted a 6-year prospective study, using multimodality ablation therapy (MMT) combined with liver transplantation (LTx) for patients with cirrhosis and unresectable HCC. Subjects were classified as: group 1 (n = 35), intention to treat with MMT + LTx; group 2 (n = 16), contemporaneous LTx with "incidental" HCC on explants; group 3 (n = 94), MMT alone; and group 4 (n = 19), palliative care alone. MMT included trans arterial chemo-embolization (54.4%), trans-arterial chemo-infusion (28.6%), and radio frequency ablation (17%). Group 1, with a mean wait time of 11.6 months pre MELD era and 5.4 months post-MELD era, had a mean of 2.4 +/- 1.2 MMTs and achieved 1- 3-, and 5-year patient survivals of 100, 100, and 76%, respectively, which was not different from group 2 (incidental HCC), namely 93, 93, and 93%, respectively; or to a contemporaneous non-HCC LTx group: namely 84.3, 78.7, and 73.9%, respectively. Despite careful pretransplant HCC staging, 22.8% (8 of 35) group 1 subjects were understaged. Those subjects in group 1 with true T1-2 stage HCC achieved 100% cancer-free survival at 5 years. Only three cases of HCC recurrence occurred in our series, all of whom were understaged. Our data suggest that pretransplant MMT followed by timely LTx provides excellent disease-free survival at 5 years for patients with true T1-2 stage HCC and cirrhosis. Pretransplant HCC understaging contributes to posttransplant HCC recurrence after LTx. PMID- 17275496 TI - Normal hepatic hemodynamics during early postoperative period in recipients with adult live donor liver transplantation. AB - To recognize "normal" hepatic hemodynamics after live donor liver transplantation (LDLT), we analyzed Doppler parameters on recipients with a right liver graft and donors after extended left hepatectomy. Theoretically these values should be the same. From April 2000 to October 2004, 20 LDLTs were performed using a right liver graft. The 10 recipients without postoperative complications and their donors were included in this study. Portal venous velocity (PVV; cm/s), hepatic arterial peak systolic velocity (cm/s), and hepatic venous peak velocity (HVPV; cm/s) were measured during the first 2 weeks. In donors PVV and HVPV after LDLT were significantly higher after than before left hepatectomy: 19.2 +/- 4.2 vs. 31.5 +/- 13.0 cm/s (P = .013) and 23.0 +/- 7.2 vs. 41.8 +/- 10.3 cm/s respectively (P = .010). However, there were mild degrees of increased PVV and HVPV. In recipients, a markedly increased PVV (106.3 +/- 45.2 cm/s on day 1) was significantly higher than that in donors on each postoperative day. The hepatic arterial resistive index in recipients was also significantly higher than that in donors on each postoperative day, for example, 0.72 +/- 0.11 vs 0.62 +/- 0.04 on day 1 (P = .0326). In conclusion, we have shown "abnormal" hepatic hemodynamics in even those recipients without complications during the early postoperative period after LDLT. PMID- 17275497 TI - Analysis of alpha-fetoprotein mRNA level on the tumor cell hematogenous spread of patients with hepatocellular carcinoma undergoing orthotopic liver transplantation. AB - The aim of this study was to detect alpha-fetoprotein (AFP) mRNA levels in the preoperative and intraoperative peripheral blood of patients with hepatocellular carcinoma (HCC) receiving orthotopic liver transplantation (OLT). METHODS: We detected AFP mRNA by TaqMan real-time reverse transcriptase-polymerase chain reactions (RT-PCR) on the peripheral blood cells (PBCs) from 30 HCC patients undergoing OLT. RESULTS: In RT-PCR, fluorescence was undetectable in any control. The positive expression rate of AFP mRNA was 23% (7 of 30) in PBC samples of OLT patients preoperatively and 50% (15 of 30) just before hepatectomy during the operation. The positive rate of AFP mRNA in OLT patients at this time was higher than that at preoperation, a difference that was statistically significant (P < .01). CONCLUSION: The OLT operation induced release of cells from the liver into the peripheral blood circulation. This may be an important mechanism of liver cancer cell dissemination deserving further investigation. PMID- 17275498 TI - Abdominal compartment syndrome secondary to retroperitoneal hematoma as a complication of ERCP after liver transplantation. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is frequently employed in the management of postoperative biliary complications in the liver transplant patient. Bleeding after ERCP most commonly presents as gastrointestinal bleeding and often can be managed with repeat endoscopy. ERCP can also be complicated by retroperitoneal hematoma, which in rare cases can lead to hemodynamic compromise due to relentless hemorrhage or from secondary abdominal compartment syndrome. We describe the first reported case of post-ERCP retroperitoneal hematoma in a liver transplant recipient that led to abdominal compartment syndrome and shock liver. We will present the case, discuss management, and review the complications of ERCP in the liver transplant recipient. Close post-procedure monitoring, rapid detection, and low threshold for decompressive laparotomy are keys to the successful management of the liver transplant recipient experiencing expanding retroperitoneal hematoma after ERCP. PMID- 17275499 TI - The expression of von Willebrand factor, soluble thrombomodulin, and soluble p selectin during orthotopic liver transplantation. AB - BACKGROUND: We evaluated von Willebrand factor (vWF), soluble thrombomodulin (sTM), and soluble P-selectin (sP-selectin) levels in ischemia/reperfusion injury during orthotopic liver transplantation (OLT). METHODS: The vWF, sTM, and sP selectin were analyzed in 20 patients who underwent liver transplantation. Blood samples were drawn from the radial artery at serial times during surgery. Plasma levels of sTM and sP-selectin were detected by enzyme-linked immunosorbent assay (ELISA). The wWF activity was measured using the immuno-turbidimetric method. Plasma aspartate transaminase (AST) and alanine transaminase (ALT) were assayed by routine clinical chemistry testing. RESULTS: Marked elevation levels of plasma AST and ALT were released during the 15 minutes after reperfusion phase, with a peak on the first postoperative day (P < .01). The sTM level remained unchanged from preoperative to anhepatic phase (P > .05). In contrast, a mean 2.5-fold increase of sTM was observed during the 15-minute reperfusion stage compared with the preoperative value (P < .01). The vWF activity only showed significant increase during the 60-minute reperfusion stage compared with the preoperative value (P < .05). No significant increase occurred in sP-seletin levels during the reperfusion phase. Platelet count showed significant decrease during the entire observation period compared with the preoperative value (P < .01). CONCLUSION: The endothelial reperfusion injury after OLT is characterized by increased vWF and sTM but not by sP-selectin in peripheral blood. PMID- 17275500 TI - Second annual analysis of the collaborative islet transplant registry. AB - In September 2001, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) founded the Collaborative Islet Transplant Registry (CITR). Each year, CITR produces a complete set of analyses available to the public. In its second year, CITR represents the efforts of 19 North American islet transplant programs reporting information on 138 islet transplant recipients (1999-2004), 256 processed pancreata that led to infusion, and 266 infusion procedures. This analysis focuses on recipients of islet-alone procedures. Median age of the recipient is 41.6 years (range, 23.1-64.4 years), duration of diabetes is 29 years (range, 4-50 years), and over 66% are female. Median weight of the recipient is 65 kg (range, 47-97 kg) and median body mass index (BMI) is 23.1 kg/m(2) (range, 18.8-31.6). Examining outcomes at 6 months following the recipient's last infusion, 67.0% are insulin independent, and at 12 months this percentage decreases to 58.0%. There is a striking decrease in the occurrence of severe hypoglycemic events subsequent to the first infusion. Over 82% of all recipients experience one or more severe hypoglycemic events in the year prior to their first infusion. However, only two recipients (2%) experience one or more severe hypoglycemic events between 30 days and 12 months postinfusion, but both of these recipients were on insulin replacement therapy and one had experienced a complete islet graft failure. The information provided in this analysis and subsequent analyses of CITR provides current and comprehensive information on outcome measures in islet transplantation. PMID- 17275501 TI - Islet yield after different methods of pancreatic Liberase delivery. AB - OBJECTIVE: Enzymatic digestion of the pancreas is a fundamental step in islet isolation and there are many ways to administer the enzyme during procurement. The aim of this study was to evaluate the influence of different methods of Liberase delivery during pancreas harvest on the quality and quantity of islets. METHODS: Depending on the type of Liberase delivery, 4 groups were created. Group 1 was intraductal, Group 2 was interstitial, Group 3 was intragallbladder, and Group 4 was no infusion of enzyme. After injection, the pancreata were harvested, digested in Liberase solution, mechanically disrupted, and purified using discontinuous gradient centrifugation. After 24-hour culture, the number, purity, and viability of the isolated islets were determined. RESULTS: Intraductal injection of the enzyme yielded statistically significantly more islets per mouse when compared with interstitial, intragallbladder, and no injection administration. Although there was a trend toward better islet purity and viability for Group 1, this was not statistically significant. CONCLUSION: Intraductal administration is the best enzyme delivery method for pancreatic islet isolation. The pancreatic ducts are the most anatomic and physiological way to transport the enzyme uniformly inside the pancreas, determining an adequate digestion and better islet quantity and quality when compared with other delivery methods. PMID- 17275502 TI - Blocking the CC chemokine receptor 5 pathway by antisense peptide nucleic acid prolongs islet allograft survival. AB - Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. The CC chemokine receptor 5 (CCR5) is the receptor for the proinflammatory chemokines and plays an important role in islet allograft rejection. Peptide nucleic acid (PNA) is a nucleic acid analog in which the sugar phosphate backbone of natural nucleic acid has been replaced by a synthetic peptide backbone. Studies indicate that PNA inhibits both transcription and translation of targeted genes. Fullly major histocompatibility complex (MHC) mismatched murine islet transplant models were used to test the in vivo effect of PNA CCR5 by targeting CCR5 in acute allograft rejection. PNA CCR5-treated recipients demonstrated significant prolongation (12.0 +/- 1.75 days) of functional allograft survival compared with saline (6.5 +/- 0.58 days)- or PNA mismatch-treated recipients (6.5 +/- 0.50 days). The PNA CCR5 blocked the expression of CCR5 in spleen CD3+ T cells. Lymphocytes from PNA CCR5-treated mice exhibited a reduced degree of proliferation comparable to that of saline- and PNA mismatch-treated mice. The present study indicated that PNA CCR5 has a substantial therapeutic effect to inhibit acute allograft rejection. PMID- 17275504 TI - Transplantation of pancreatic islets from hypothalamic obese rats corrects hyperglycemia of diabetic rats. AB - Pancreatic islets isolated from adult obese rats, obtained by neonatal treatment with monosodium L-glutamate (MSG), oversecrete insulin stimulated by glucose concentration. Whereas adult MSG obese rats are hyperinsulinemic, their pancreatic islets still secrete insulin after high glucose demand. This is crucial so that the animals do not become hyperglycemic. Islets from MSG obese rats were implanted in diabetic donor rats so that the capacity of islets in regulating blood glucose concentration could be evaluated. Hyperglycemic (glucose 22 to 34 mmol/L) rats obtained with streptozotocin (STZ) treatment were used as recipients. Islet donors consisted of control adult and MSG obese rats. Only 600 islets were transplanted via the portal vein to diabetic rats. During 4 days after the transplant, fed blood glucose was monitored. After 12 hours of fasting the rats were killed; their blood samples were used to measure glucose and insulin concentration; retroperitoneal fat pads were isolated and weighed to estimate body fat. Transplanted islets from MSG obese rats decreased of fed glucose levels by 34% in diabetic rats (P < .05); however, glucose levels still remained twofold higher than those of intact controls (P < .05). Similar to MSG islets, islets grafts from control rats provoked the same effects in diabetic rats. High fasting blood glucose and low insulin levels of diabetic rats were corrected by islet grafts. Transplantations were able to recover 40% of fat in diabetic rats. The results demonstrated that islets from MSG obese rats may regulate blood glucose concentrations in diabetic rats, and suggesting that their function was not permanently altered by the onset of obesity. PMID- 17275503 TI - Subcutaneous pancreatic islet transplantation using fibrin glue as a carrier. AB - BACKGROUND: Pancreatic islet grafts are difficult to manipulate and implant in the recipient site mainly because they are formed by a group of cells suspended in a solution. This physical property determines various characteristics that are unique for pancreatic islet transplantation. The purpose of this study was to evaluate the role of fibrin glue as a delivery method for islet transplantation. METHODS: C3H mouse islets were syngeneically transplanted into streptozotocin diabetic recipients using fibrin glue in a subcutaneous pocket (Group 1) and using liquid islets injected under the kidney capsule (Group 2). Blood glucose levels were measured during 4 weeks of follow-up and compared against normal (Group 3) and diabetic levels (Group 4). RESULTS: No statistical differences were observed between the normal, kidney capsule, and fibrin glue groups. Only the diabetic group had a statistical difference when compared with the normal control group (P < .01). At the beginning, levels in Group 1 (fibrin glue) were higher than in Group 2 (kidney capsule), but turned into similar values after time and no statistical differences were observed between them during follow-up. CONCLUSIONS: Islet/fibrin glue grafts placed in a subcutaneous pocket obtained the same results as liquid grafts placed under the kidney capsule, proving to be an adequate delivery method for islet transplantation and solving some of the engraftment problems we find with liquid grafts. PMID- 17275506 TI - Retrospective analysis of early steroid-induced adverse reactions in kidney and kidney-pancreas transplant recipients. AB - Corticosteroids (steroids) are associated with numerous adverse drug reactions (ADRs). Long-term ADRs are well characterized, but there are limited data on the incidence and likelihood of short-term ADRs. We sought to determine the incidence of ADRs potentially related to early administration of steroids in kidney and kidney-pancreas transplant recipients and to determine the probability that the ADR was due to the steroid. We retrospectively evaluated the records of all eligible kidney or pancreas-kidney transplants during 2003. ADRs were rated by two reviewers according to the Naranjo algorithm, and identified as "definite," "probable," "possible," or "doubtful." ADRs were identified in 100% of patients (n = 103) by 8.2 +/- 4.9 days. The mean ADRs per patient were 3.26 +/- 1.04. Weight gain occurred in 79.6%, hypertension in 71.8%, diabetes mellitus in 52.4%, hyperglycemia in 47.6%, leukocytosis in 31.1%, insomnia in 27.2%, anxiety in 10.7%, and psychosis in 1.9%. Based on mean interinvestigator score, leukocytosis was judged as "probable" and weight gain and psychosis were "possible to probable." Diabetes, hyperglycemia, hypertension, and insomnia were "possible" and anxiety was "possible to doubtful." These results provide evidence of the incidence and likelihood of early steroid-related ADRs. PMID- 17275505 TI - Bezoar-related pancreatitis in enterically drained pancreas transplant. AB - Simultaneous kidney and pancreas transplantation is currently the treatment of choice for type 1 diabetes mellitus with end-stage renal disease. As a result of improvements in surgical techniques and the efficacy of immunosuppression, patient and graft survival rates have improved dramatically over the last two decades. Despite this, it remains a challenging surgical procedure with many potential complications and occasional controversies. Causes of pancreatitis after pancreas transplantation with enteric drainage are not well documented in the literature. We report a case of allograft pancreatitis from pancreatic duct outflow obstruction due to formation of a bezoar in a diverticulized transplant duodeno-jejunal anastomosis. To the best of our knowledge, this is the first case of allograft pancreatitis reported in the literature occurring from bezoar formation. PMID- 17275507 TI - Induction therapy in lung transplantation: initial single-center experience comparing daclizumab and antithymocyte globulin. AB - Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. Because acute rejection is associated with inferior outcomes in lung transplantation, we have routinely employed antithymocyte globulin (ATG) or daclizumab as adjuncts to reduce the incidence of rejection episodes. METHODS: We performed a controlled clinical trial of the two therapies to evaluate differences in postoperative rejection, infection, bronchiolitis obliterans syndrome (BOS) and host survival. Twenty-five consecutive lung transplant patients received ATG (n = 12; group 1) or daclizumab (n = 13; group 2) as an induction agent. The groups showed similar demographics and immunosuppression protocols, differ only in induction agent. RESULTS: No differences were observed in the immediate postoperative outcomes, such as length of hospitalization, ICU stay, or time on ventilator. There were no significant differences in the number of episodes of acute rejection, freedom from BOS, or infections. Freedom from acute rejection was significantly greater with daclizumab than with ATG (P = .037). The 1-year survival for group 1 was 67% and for group 2, 77% (P = .584). CONCLUSIONS: Daclizumab constitutes a safe and effective form of induction immunosuppressive therapy. Using a two-dose administration schedule, daclizumab prolonged the time without acute rejection compared to ATG. The differences in the incidence of infectious complications, acute rejection, or BOS as well as the short-term or long-term results were not significantly different. The results of the study justify the further use of daclizumab as an induction agent in patients following lung transplantation. PMID- 17275508 TI - Peripheral CD4(+)CD25(+) TREG cell counts and the response to extracorporeal photopheresis in lung transplant recipients. AB - Extracorporeal photopheresis (ECP) has been proposed as a possible alternative therapy for patients with bronchiolitis obliterans syndrome (BOS), with some evidence of efficacy. Although the mechanism by which ECP exerts its protective effects remains to be determined, two recent studies suggest that the modulation of transplant immune rejection may depend on the capacity to increase the number of peripheral T-regulatory (Treg) cells. We evaluated the effect of ECP treatment on the number of naturally occurring CD4(+)CD25(+) Treg cells in the peripheral blood of six lung transplant recipients: in five cases after failure of augmented or changed immunosuppression for BOS, and in one case owing to persistent acute rejection in a patient who contracted chronic hepatitis C viral infection after lung transplant. A functional stabilization was observed in three of our five patients with BOS, which was accompanied by a slight increase or stabilization of the number of peripheral blood CD4(+)CD25(high) cells with in vitro features of Treg cells. On the contrary, two patients with BOS who did not experience graft functional stabilization also showed a decline in the peripheral Treg subset. In the last patient Treg cell kinetics showed stabilization during the first 5 months of ECP treatment when lung function remained stable and graft histology normalized but showed a subsequent decrease, predating BOS diagnosis. In all, our results indicate that ECP may modulate peripheral Treg cell number but the time course of peripheral Treg cells varies according to graft function. PMID- 17275509 TI - Differential white cell count relationships with human cardiac allograft rejection. AB - The focus of research in allograft rejection has targeted the lymphocyte, with little attention given to the neutrophil. Recent data indicate that a perioperative neutrophil influx into the cardiac allograft influences early rejection. Factors that influence neutrophil transendothelial migration might offer predictive markers of rejection. We explored the relationship between the number of circulating neutrophils in heart transplant recipients and the development of rejection. Differential white cell counts were obtained prior to transplantation and concurrently with subsequent endomyocardial rejection surveillance biopsies for 53 heart transplant recipients undergoing 410 biopsies. Preoperative differential white cell counts had no relationship with rejection. In the first 3 months after transplantation, no relationship was found between contemporary differential white cell counts and rejection. However, more than 3 months following surgery, rejection grade positively correlated on univariate analysis with neutrophil counts and the usage of cyclosporine, prednisolone, and mycophenolate. There was no relationship with eosinophils or lymphocytes. Multivariate analysis demonstrated a persistent relationship among rejection severity, neutrophil count, and prednisolone usage. A significant positive association of higher steroid usage with higher rejection grades must reflect efforts to treat patients with rejection. The significant association of higher neutrophil counts with higher rejection severity might suggest a pathological contribution to rejection. However, given the neutrophilia response to acute steroid administration, we must conclude that the neutrophil association was related to steroid administration. The absence of a relationship between white cell counts and rejection suggests that functional rather than antiproliferative strategies may offer the greatest therapeutic potential. PMID- 17275510 TI - The impact of single parathyroid gland autotransplantation during thyroid surgery on postoperative hypoparathyroidism: a multicenter study. AB - BACKGROUND: We compared the surgical outcomes in patients undergoing bilateral thyroid surgery with or without parathyroid gland autotransplantation (PTAT). METHODS: One thousand three hundred nine patients underwent surgery for treatment of various thyroid diseases at three Academic Departments of General Surgery and one Endocrine-Surgical Unit throughout Italy. A nonviable gland or difficulties in dissection of the parathyroid glands were encountered in 160 (13.7%) patients. The subjects were divided into two groups: (1) patients undergoing PTAT during thyroidectomy (n = 79) versus (2) control group (n = 81), patients not undergoing PTAT. RESULTS: Clinical manifestations occurred in 5.0% of PTAT patients and in 13.6% of control patients (P = NS). Total postoperative hypocalcemia was less among PTAT than control patients (17.7% and 48.1%, respectively; P = .0001). There was no significant difference between the two groups in terms of definitive hypocalcemia (0% vs 2.5% in PTAT and control, respectively). Transient postoperative hypocalcemia was less among PTAT than controls (17.7% vs 45.7%; P = .0002). PTAT was associated with decreased occurrence of hypocalcemia in the two subgroups of patients operated for benign euthyroid disease (P < .0001), as compared with the control group. CONCLUSIONS: PTAT is an effective procedure to reduce the incidence of permanent hypoparathyroidism. Transient hypoparathyroidism appears to not be influenced by PTAT. Moreover, we observed that damage to one parathyroid gland has more side effects (ie, transient hypocalcemia) among patients who were preoperatively at low rather than at high risk of postoperative hypocalcemia. PMID- 17275511 TI - Liver chimerism after allogeneic blood stem cell transplantation. AB - Blood stem cells can mature into elements of many different lineages. We investigated the presence and nature of donor-derived (chimeric) cells within the liver after allogeneic stem cell transplantation. METHODS: Liver biopsy autopsy specimens were examined from nine female patients who had undergone allogeneic bone marrow (n = 6) or peripheral stem cell (n = 3) transplantation from a male donor. To identify the male origin of cells within the liver, in-situ hybridization for Y-chromosomes was performed in conjunction with CD45 staining to identify leucocytes. RESULTS: Hematopoietic stem cell engraftment was confirmed in all nine recipients. Histologic examination of the liver tissue sections revealed 5.6-fold more Y-chromosome-positive than CD45-positive staining cells (P < .02), indicative of considerable nonleucocytic chimerism. This was particularly observed in patients who had developed graft-versus-host disease. CONCLUSIONS: Donor-derived cells can be found in liver tissue specimens after allogeneic stem cell transplantation. A considerable fraction of chimeric (donor derived) cells appeared to be of nonlymphohematopoietic origin. This finding supports the theory of blood stem cells developing into liver cells of mesenchymal origin. PMID- 17275513 TI - Human cord blood cells transplanted into chronically damaged liver exhibit similar characteristics to functional hepatocytes. AB - Human umbilical cord blood (CB) cells have many advantages as a source for stem cell transplantation because of immaturity and availability. It has been reported that CB cells transplanted into an injured liver displayed hepatocyte-like phenotypes. However, there have been few studies to characterize CB-derived hepatocyte-like cells (HLCs). In this study, CB cells were transplanted into mice with 2 types of liver damage: transient and chronic damage. We analyzed the expression of hepatic differentiation markers in CB-derived HLCs. In the liver of NOD/SCID mice with transient damage, CB-derived HLCs were detected infrequently at 3 weeks after transplantation. In contrast, in the liver of SCID mice damaged chronically by a urokinase-type plasminogen activator transgene under the control of albumin promotor/enhancer (ALB-uPA/SCID mice), more human HLCs colonized the host liver compared with hosts with transiently damaged livers. The CB-derived HLCs in both the transiently and the chronically damaged liver expressed a few markers of human hepatocytes, whereas the transcripts related to mature hepatic functions, including cytochrome P450s, were detected only in the ALB-uPA/SCID mice. These data indicated that CB cells were able to display a similar phenotype to functional hepatocytes in the recipient liver with chronic damage. CB cells may represent a transplantable source for chronic decompensated liver disease. PMID- 17275512 TI - Safety and efficacy of foscarnet for preemptive therapy against cytomegalovirus reactivation after unrelated cord blood transplantation. AB - In association with the increased use of unrelated cord blood transplantation (UCBT) in adults, numerous patients have developed cytomegalovirus (CMV) reactivation concomitant with cytopenia. Although foscarnet appears to offer similar efficacy and higher safety as a preemptive therapy against CMV infection than ganciclovir, little is known about the usefulness of foscarnet in such patients. Foscarnet was administered as preemptive therapy against CMV antigenemia in 10 UCBT recipients who were unable to receive ganciclovir due to cytopenia or poor response to ganciclovir. Fatal CMV disease developed in one patient, whereas CMV antigenemia resolved without progression to CMV disease in the remaining nine patients. Foscarnet was well tolerated without serious hematotoxicity and was not discontinued due to adverse events in any patient. Foscarnet represents a safe and effective agent for preemptive therapy against CMV infection and may offer a feasible alternative to ganciclovir in UCBT recipients. PMID- 17275516 TI - Measurement of radical-scavenging ability in small bowel ischemia/reperfusion injury in rats using an in vivo and ex vivo electron paramagnetic resonance technique. AB - Reperfusion of ischemic tissues results in the formation of toxic reactive oxygen species (ROS), such as superoxide anion, hydroxyl radicals, hydroperoxide, and peroxynitrite. ROS are potent oxidizing agents, fully capable of damaging cellular membranes by lipid peroxidation. In this study, we applied for the first time the in vivo electron paramagnetic resonance (EPR)/spin probe and ex vivo EPR technique to provide direct evidence of ROS following experimentally induced small bowel ischemia/reperfusion (I/R) injury. The decay rate (spin clearance rate) was determined over the first 3 minutes at 6 hours after reperfusion. Decay rates in rats subjected to I/R injury were lower than those in the sham group. Superoxide scavenging activity (SSA) in rats subjected to I/R injury was significantly lower than that in the sham group. In conclusion, this study demonstrated that it is possible to detect the accumulation of ROS following experimentally induced small intestine I/R injury using an in vivo and an ex vivo EPR technique with a spin probe. PMID- 17275515 TI - Antioxidant patterns (superoxide dismutase, glutathione reductase, and glutathione peroxidase) in kidneys from non-heart-beating-donors: experimental study. AB - INTRODUCTION: The evolution of renal antioxidant concentrations in the different phases of a non-heart-beating donor (NHBD) transplant after prolonged warm ischemia (40 and 90 minutes) and the effect of normothermic extracorporeal recirculation (37 degrees C) for 30 minutes were evaluated on antioxidant tissue concentrations in the kidney. METHODS: Forty pairs of pigs, were divided into groups of 10 as follows: group 0, control donor with beating heart; group 1, 40 minutes of warm ischemia without recirculation by cardiopulmonary bypass pump (groups 2 and 3); group 2, 40 minutes of warm ischemia and recirculation for 30 minutes at 37 degrees C; and group 3, 90 minutes of warm ischemia and recirculation for 30 minutes at 37 degrees C. The concentrations of superoxide dismutase (SOD), glutathione peroxidase, and glutathione reductase were determined at the tissue level by biopsy at baseline the end of warm ischemia, the end of recirculation, at the end of cold ischemia, and 1 hour after reperfusion. RESULTS: SOD was consumed at the end of the cold ischemia phase (P < .009) and increased during reperfusion (P < .02). Glutathione reductase was consumed during the cold ischemia phase (P < .04). In kidneys submitted to 40 minutes of warm ischemia, SOD was consumed during the cold ischemia phase (P < .04) and increased with reperfusion (P < .03). In kidneys undergoing 90 minutes of hot ischemia, SOD was consumed during cold ischemia (P < .04) and glutathione reductase during extracorporeal recirculation (P < .01). CONCLUSIONS: Recirculation increased the tissue level of SOD at the end of the cold ischemia period. PMID- 17275517 TI - Effects of hypothermic perfusion in isolated pig kidneys after warm ischemia. AB - An experimental study in pigs was designed to evaluate the consequences of normothermic ischemia in hypothermic isolated renal perfusion (HP). We perfused 16 kidneys after 45 minutes of vascular occlusion. Another 16 kidneys were perfused without previous warm ischemia. The ureter was catheterized in all procedures and the output collected during HP. Creatinine was added to the perfusion solution initially in order to determine creatinine clearance (CrCl). HP hydrodynamics were recorded in real time through a computerized system. According to the results, renal vascular resistance as well as CrCl were higher in ischemic kidneys. Both facts, along with minimal differences in the microscopic study, suggested an increased vascular tone of the efferent postglomerular arteriole during HP. HP was proven to be an optimal technique to minimize the histological consequences of ischemia. Microvascular and biochemical changes produced during HP may be essentially related to dynamic causes. PMID- 17275514 TI - Effect of the immunoregulatory cytokines on successful pregnancy depends upon the control of graft rejection mechanisms. AB - Successful outcomes in allopregnant women depend upon control of graft rejection mechanisms. An understanding of how the fetus escapes the maternal immune system may be relevant for the prevention of transplant rejection. It has been suggested that the same immunosuppressive cytokines contribute to successful pregnancy and transplantation. Recent reports suggest a role for transforming growth factor beta (TGF-beta) in the generation of T-regulatory lymphocytes. In contrast, production of proinflammatory cytokines accompanying intrauterine infection has been associated with fetal rejection or preterm labor. Interleukin-12 (IL-12) is the unique stimulator for differentiation of T-helper lymphocytes (Th) to Th1 cells. It rapidly induces transcription of Th1 cytokines such as interferon gamma. This study was performed in 70 pregnant women at 21 to 36 weeks gestation, and in 32 healthy nonpregnant controls. An indirect enzyme-linked immunosorbent assay was used to estimate TGF-beta1, and IL-12 in serum. The results showed that TGF-beta1 levels were higher in all pregnant women compared with the nonpregnant controls. No significant changes in serum levels of IL-12 were observed in pregnant compared with the normal control women. The results suggested that the cytokine milieu of the placenta appeared to play a critical role in the maternal acceptance of the fetus, and that TGF-beta1 may function as a regulatory factor in fetal allograft survival during pregnancy. PMID- 17275518 TI - Chlamydia pneumoniae infection is not associated with chronic transplant dysfunction in a rat aortic allograft model. AB - Long-term survival of solid-organ transplants is limited as a result of chronic transplant dysfunction (CTD), which is characterized by occlusion of intragraft vascular tissue due to myointimal hyperplasia. Recent studies have shown a role for infections in vascular pathologies. For example, Chlamydia pneumoniae (Cpn) has been shown to aggravate atherosclerosis, and Cpn immunoglobulin (Ig)G titers correlate with severity of allograft atherosclerosis after cardiac transplantation. In this study, we evaluated the effect of Cpn infection on CTD using a rat aortic allograft model. Orthotopic abdominal aorta transplantations (Tx) were performed with Brown Norway rats as donors and Lewis rats as recipients. Rats were humanely killed at 1 or 8 weeks after surgery. The graft was processed for DNA isolation and histological examination. Influx of macrophages and T cells was assessed using immunohistochemistry. At 1 week after Tx, the perivascular influx of inflammatory cells in the graft was not affected by Cpn infection. Furthermore, only limited numbers of Cpn DNA copies were found in the graft at 1 week after Tx. In addition, Cpn did not alter the severity of myointimal hyperplasia in the rat aortic allograft model at 8 weeks after surgery. Our data suggested that, in the rat aortic allograft model, Cpn infection did not influence the influx of inflammatory cells or the severity of CTD. PMID- 17275519 TI - SDF-1 plays a key role in the repairing and remodeling process on rat allo orthotopic abdominal aorta grafts. AB - BACKGROUND: Our previous study demonstrated that prolonged cold preservation promoted neointima formation and remodeling but delayed the subsequent arteriosclerosis of rat abdominal aorta grafts. The mechanisms of this phenomenon remain obscure. In this study, we investigated whether stromal cell derived factor-1 (SDF-1) could play a role in recruiting stem cells to repair and remodel the damaged intima of abdominal aorta grafts. METHODS: Male Spague-Dawley rats received abdominal aorta grafts from male Wistar rats. Hematoxylin and eosin staining was performed to assess the structure of graft aortas by measuring the neointimal thickness. Immunohistochemical staining detected SDF-1 expression. RT PCR demonstrated the expression of CXCR4, the only known natural receptor of SDF 1 expression on stem cells. RESULTS: The neointimal thickness of the SDF-1 antibody-treated group was inconspicuous; a significant relationship existed between the expression of SDF-1 and the neointimal thickness of the grafts. Furthermore, no CXCR4 was detected in normal abdominal aortas, but it was observed in the grafted abdominal aorta. CONCLUSION: Prolonged cold ischemia may delay the graft's arteriosclerosis by selectively chemoattracting stem cells to the damaged intima through SDF-1, the presence of which may predict graft arteriosclerosis and the subsequent development of chronic graft dysfunction (CGD). The SDF-1 antibody slowed the endothelial chimerism by blocking this chemoattration. In addition to mycophenolate mofetil and FK 506, SDF-1 antibody might be a new potential effective strategy to decrease the frequency of CGD. PMID- 17275520 TI - Orthotopic abdominal multivisceral transplantation without venovenous bypass in pigs. AB - BACKGROUND: Because venovenous bypass (VVB) can cause specific complications, a simplified orthotopic abdominal multivisceral transplantation (MVTX) technique without VVB in pigs has been evaluated in terms of morbidity and mortality. MATERIALS AND METHODS: Outbred large-white pigs weighing 25 to 40 kg of random sex underwent MVTX operation. After in situ cold perfusion through the aorta and superior mesenteric vein, the multivisceral allograft was procured from the donor and tailored at the back table. The multivisceral allograft, including liver, pancreas, stomach, duodenum, and proximal 2 m of jejunum, was en bloc transplanted into recipient after resection of entire foregut and midgut; VVB was not used. We analyzed the hemodynamic change, arterial blood gas data, and fluid requirements intraoperatively. RESULTS: Among 25 MVTXs, 19 (76%) animals survived after the operation. Without using an immunosuppressant, postoperative survival time was 2 to 146 hours. Ten recipient pigs died within 24 hours. Seven animals were lost between postoperative days 2 and 5. Two pigs survived for more than 5 days. The recipient pigs were mostly in a state of hypovolemic shock and metabolic acidosis during the reperfusion phase. CONCLUSIONS: Despite a high morbidity and mortality, the simplified technique without VVB is feasible to successfully achieve MVTX in the pig. PMID- 17275521 TI - The establishment of a new en bloc combined liver-small bowel transplantation model in rats. AB - In order to facilitate preclinical research, we established a new combined liver small bowel transplantation rat model. Male inbred Wistar rats were chosen as donors and recipients. An en bloc liver-small bowel graft was harvested. During the donor operation, the inferior vena cava in the chest was removed to be used as an interpositional venous graft to anastomose to the portal vein. In the recipient operation the portal veins of donor and recipient were quickly anastomosed using a cuff technique instead of the traditional suture method. Rearterialization was achieved by anastomosing the superior mesenteric artery of graft to the right renal artery of the recipient. The recipient small bowel was resected and intestinal continuity restored simultaneously by two end-to-end anastomoses. The postoperative 5-day survival rate was 77.5% (31/40) and 60-day survival rate, 72.5% (29/40). Recipient rats that tolerated the operation remained healthy. Liver and renal function was normal. The liver and intestinal grafts showed normal histological architecture in all rats surviving for 2 months postoperatively. Our results demonstrated that the present model is feasible, allowing preclinical experimental research on combined liver-small bowel transplantation. PMID- 17275522 TI - Cross-tolerance of recipient-derived transforming growth factor-beta dendritic cells. AB - Administration of donor-derived immature dendritic cells (DC) treated with transforming growth factor-beta (TGF-beta) to prevent allograft rejection is not applicable for clinical use. We therefore attempted to explore the use of recipient-derived DC pulsed with donor antigens via the indirect pathway (cross priming). DC were propagated from C3H (H2(k)) bone marrow (BM) using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). TGF-beta (0.2 ng/mL) was added at the initiation of culture. The resultant TGF-beta DC were pulsed with B10 (H2(b)) splenocyte lysate. Expression of major histocompatibility complex (MHC) class I and II was not affected, while CD40, CD80, and CD86 costimulatory molecules on DC were significantly inhibited by treatment with TGF-beta. C3H DC pulsed with B10 antigens stimulated a proliferative response in C3H T cells which was inhibited when DC were treated with TGF-beta, and the cytotoxic T-lymphocyte (CTL) activity was also inhibited. This observation correlated with reduced interferon-gamma (IFN-gamma) and increased IL-10 production. A single injection of TGF-beta DC prolonged allograft survival (median survival time [MST] 18 days vs 10 days in no-DC treatment control; P < .05). These data indicated that an approach utilizing recipient DC as a "vaccine" strategy is possible. PMID- 17275524 TI - Combination treatment with donor interleukin-12p35 silenced dendritic cells and cyclosporine induces long-term survival of intestinal allografts in rats. AB - Immune tolerance promises to enhance allograft survival while reducing risks inherent to immunosuppressants. In this study, we evaluated the effect of interleukin (IL)-12p35 silenced dendritic cells (DC) combined with cyclosporine (CsA) on induction of immune tolerance in intestinal transplantation. The results showed that combination treatment with donor IL-12p35 silenced DC and a low dose of CsA (8 mg/kg) prolonged rat intestinal allograft survival. However, a higher dose of CsA (20 mg/kg) did not further prolong allograft survival. PMID- 17275523 TI - Lipid-mediated transbronchial human interleukin-10 gene transfer decreases acute inflammation associated with allograft rejection in a rat model of lung transplantation. AB - BACKGROUND: Transferring genes with immunoregulatory capacity to transplanted organs has the potential to modify allograft rejection (AR). We examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on acute AR in a rat model of lung transplantation. METHODS: Left single lung transplantations were performed between a highly histoincompatible rat combination: Brown Norway to Lewis. The extracted donor left lung was intrabronchially instilled with a plasmid encoding hIL-10 or Escherichia coli beta-galactosidase (control), mixed with a cationic lipid. On day 6 posttransplantation, the degree of AR was graded histologically (stages 1-4) based upon pathological categories of inflammation: perivascular, peribronchial, and peribronchiolar lymphocytic infiltrates, edema, intraalveolar hemorrhage, and necrosis. RESULTS: The stage of AR in the IL-10 group (3.1 +/- 0.4) was significantly lower than the control group (3.8 +/- 0.4). Pathological scores for edema, intraalveolar hemorrhage, and necrosis in the IL-10 group (2.3 +/- 0.8, 0.3 +/- 0.5, and 0.3 +/- 0.5, respectively) were also significantly decreased compared with those in the control group (3.2 +/- 0.4, 2.2 +/- 0.8, and 1.2 +/- 0.4, respectively). CONCLUSION: Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR in a rat model of lung transplantation. PMID- 17275525 TI - Intestinal tight junction in allograft after small bowel transplantation. AB - INTRODUCTION: In the intestinal physical barrier, tight junctions between intestinal epithelial cells play a central role. There is increasing evidence that rejection after small bowel transplantation promotes intestinal barrier injury to allografts. Our aim was to study the morphological changes of tight junctions in allografts during rejection. METHODS: Small bowel transplantation was performed using the F344 to Lewis rat model. Animals were divided into three groups: isogeneic controls, acute rejection group, and chronic rejection group. Allograft rejection was characterized by hemotoxylin and eosin staining of mucosal tissue sections. Tight junctions in grafts were investigated by transmission electron microscopy. RESULTS: Acutely rejected allografts showed severe mucosal injury and completely loosened tight junctions, while chronically rejected allografts revealed less mucosal injury and remained with partial integrity of their tight junctions. CONCLUSION: Our study demonstrated for the first time the morphological alterations of tight junctions in allograft mucosa during acute and chronic rejections, suggesting disruption of tight junctions was relative to the intestinal inflammatory processes. PMID- 17275526 TI - Acute influence of FK506 on T-lymphocyte populations of peripheral blood and spleen in rats. AB - BACKGROUND: Tacrolimus (FK506) is an immunosuppressive agent used in clinical transplantation. We studied the acute impact of FK506 on T-lymphocyte populations of peripheral blood and spleen in rats. METHODS: The animals injected with FK506 (2 mg/kg) subcutaneously were sacrificed at 12, 24, or 48 hours after administration. CD3(+), CD4(+) and CD8(+) T-cell populations in peripheral blood and spleen were analyzed by FACS. RESULTS: After treatment with FK506, the proportion of CD4(+) cells significantly increased in the spleen at 12 hours, decreasing to control levels at 24 and 48 hours. There was a slight increase in the CD4(+) subpopulation in the peripheral blood at 12 and 24 hours and a significant increase at 48 hours. The CD8(+) T-cell subpopulations in peripheral blood and spleen were stable during FK506 administration. CONCLUSIONS: These results indicated that FK506 increased CD4(+) spleen lymphocyte activation in a short time, inducing a subsequent increase in CD4(+) cells subsets in peripheral blood. PMID- 17275527 TI - Intraabdominal bleeding following simultaneous pancreas-kidney transplantation treated with angiographic embolization. AB - Significant early bleeding is one of the surgical complications following simultaneous pancreas-kidney transplantation that has historically shaped the procedure. The consequence, exploratory laparotomy, carries high morbidity levels and elevated costs for the health system. Angiographic intervention is already a common procedure for the treatment of late, but not early, vascular complications. We describe a case of an early vascular complication that was successfully treated with angiographic embolization in a to simultaneous pancreas kidney transplant patient. PMID- 17275529 TI - Subcapsular nephron-sparing surgical approach for small renal graft tumor: a case report. AB - Conservative treatment of renal cell cancer in kidney grafts is rare. Only six reports have been presented in the literature regarding nephron-sparing surgery in this setting. We report the case of a 38-year old man with a kidney transplant from a 72-year-old donor 2 years prior. Ultrasonography detected a renal exophytic mass (2 cm) in the lower pole, which was treated with open tumor enucleation by a subcapsular approach. No vascular clamping was performed, and minimal bleeding occurred. The kidney graft is well functioning, with serum creatinine of 1.6 mg/dL. The histological diagnosis was cromophyle renal adenocarcinoma. PMID- 17275528 TI - Effect of total enterectomy, pancreatectomy, and portal vein ligation on liver function and histology: a case report. AB - Impaired hepatic function and histology have been observed in experimental models of diversion of the portal vein blood inflow from the liver and among patients with intestinal failure. Survival after total enterectomy, pancreatectomy, and portal vein ligation, and the effect of such a condition on liver function have never been reported in humans. Herein a 32-year-old woman with familial adenomatous polyposis and multiple desmoid tumors involving the mesentery and the retroperitoneum underwent total enterectomy and pancreatectomy followed by en bloc transplantation of the stomach, small bowel, and pancreas. Due to early graft failure, the patient underwent graftectomy, ligation of the portal vein, and external drainage of the common bile duct. Liver function tests were checked daily and a liver biopsy performed 15 days after graftectomy. The patient died of a ruptured mycotic aneurysm of the abdominal aorta at 27 days after the graftectomy. Liver function tests remained normal throughout the postoperative period; liver biopsy showed normal hepatic architecture with mild portal inflammation and cholestasis and spotty necrosis. Total enterectomy with pancreatectomy and ligation of the portal vein are compatible with survival in humans (at least in the short term), allowing normal hepatic function with minimal histological alterations to the liver. PMID- 17275530 TI - Survival after disseminated invasive aspergillosis in a multivisceral transplant recipient. AB - Disseminated invasive aspergillosis is a serious and potentially lethal infectious complication of immunosuppressed individuals, including transplant recipients. We report here a successfully treated case of disseminated Aspergillus fumigatus infection involving the lungs, brain, and endocardium in a multivisceral transplant recipient. In addition to supportive measures, the patient was aggressively treated with a combination of three antifungal agents, and all immunosuppression was significantly lowered with close observation for rejection. After 3 months of therapy, the patient cleared the fungal infection, made a full recovery of his cerebral function, and was discharged to a rehabilitation facility. PMID- 17275531 TI - Nesiritide as bridge to multi-organ transplantation: a case report. AB - Nesiritide, an intravenous form of human B-type natriuretic peptide, has been approved as treatment for patients with acute decompensated heart failure. Due to its action on different receptors, nesiritide has many effects, including vasodilation and natriuresis. Cardiac preload and afterload decrease, leading to an increase in cardiac output through effects on smooth muscle and the kidneys. As a bridge to cardiac transplantation, nesiritide has been used to maintain vasodilation and diuresis without sacrificing kidney function. Our patient, prior to multi-organ transplantation, had a pulmonary capillary wedge pressure of 41 mm Hg on milrinone monotherapy, which decreased slightly with nitroprusside and further decreased to 4 mm Hg after the addition of nesiritide. The patient's measured creatinine clearance level was calculated to be 40 mL/min. When nesiritide therapy was begun, the renal function did not improve, but, as the hemodynamics improved, renal function did not decrease. PMID- 17275532 TI - High suspicion of bacillary angiomatosis in a kidney transplant recipient: a difficult way to diagnose--case report. AB - Bacillary angiomatosis is an infection caused by Bartonella, which has first been described in human immunodeficiency virus (HIV)-infected patients. We report an unusually located lesion, in a totally asymptomatic kidney transplant recipient. The diagnosis was strongly suggested based on the iconography and our histological analysis, but was not confirmed using polymerase chain reaction (PCR) and immunohistochemical studies. We illustrate our difficult way to the diagnosis as well as the course of the disease and our therapeutic strategy. PMID- 17275533 TI - Caregiver well-being and child quality of life. AB - OBJECTIVE: To describe the impact of otitis media on the child's family and caregiver, and how this impact influences the caregiver's perception of child's quality of life (QOL) and functional health status (FHS). STUDY DESIGN AND SETTING: Prospective study of children aged 6 months to 12 years with recurrent or chronic otitis media recruited from a primary care pediatrics practice and a referral-based pediatric otolaryngology practice. Survey measures were assessed for test-retest reliability, internal consistency, and validity. Multiple regression analysis was used to explore relationships. RESULTS: We enrolled 159 families, with mean age of 3.3 years for the child and 34 years for the caregiver. Most caregivers attended college (80%) and 64% were employed. The Caregiver Impact Questionnaire (CIQ) had good test-retest reliability (r=0.83), internal consistency (alpha=0.88), and construct validity (r=0.37 to 0.62). Most caregivers (52%) were nervous or agitated at least "some of the time" because of their child's ear problems, 29% lost sleep "a good bit of time," and 56% had to change daily activities. Multivariate analysis showed that caregiver QOL explained 62% of variability in child disease-specific QOL, and that caregiver FHS explained up to 45% of the variability in child FHS. CONCLUSION: The 6-item CIQ survey permits a valid and reliable assessment of otitis media impact on caregivers and family functioning. Caregiver ratings of child QOL and FHS are largely influenced by caregiver perceptions of their own personal situation. SIGNIFICANCE: The caregiver QOL and FHS should be considered when using proxy completed surveys to assess the impact of otitis media on children. PMID- 17275534 TI - Adenotonsillectomy and obstructive sleep apnea in children: a prospective survey. AB - OBJECTIVE: Prospective survey of children up to 14 years of age with OSA submitted to adenotonsillectomy. METHODS: Clinical evaluation, with questionnaires and clinical scales evaluating facial structures including tonsils and Mallampati scales and otolaryngologic evaluation; nocturnal polysomnography and repeat evaluation three to five months postsurgery. RESULTS: Of 207 successively seen children, 199 had follow-up polysomnography, and 94 had still abnormal sleep recording. Multivariate analysis indicates that Mallampati scale score 3 and 4, retro-position of mandible, enlargement of nasal inferior turbinates at +3 (subjective scale 1 to 3), and deviated septum were significantly associated with persistence of abnormal polysomnography (with high 95% CI for Mallampati scale and deviated septum). CONCLUSION: Mallampati scale scores are resultant of several facial factors involving maxilla, mandible, and oral versus oral breathing but add information on risk of partial response to adenotonsillectomy. SIGNIFICANCE: Adenotonsillectomy may not resolve obstructive sleep apnea in children. PMID- 17275535 TI - Increased incidence of head and neck abscesses in children. AB - OBJECTIVE: To describe increasing incidence and changing microbiology of head and neck abscesses in children admitted to the hospital during the first quarters of 2000 through 2003. STUDY DESIGN AND SETTING: Retrospective data warehouse review identified 89 children less than 19 years of age admitted to a tertiary care pediatric hospital during the first quarters of 2000 through 2003 for suspicion of head and neck abscess involving the neck, face, and peritonsillar, retropharyngeal, and parapharyngeal spaces; and for orbital and intracranial complications of acute sinusitis. OUTCOME MEASURES: Outcome measures included the incidence of infection admissions and description of infection location and microbiology, calculated by chi2 technique. RESULTS: The incidence of infections increased in 2003. The greatest increase was in neck abscesses and complications of acute sinusitis. CONCLUSIONS: The increase in group A strep infections may be related to its biologic properties. SIGNIFICANCE: Group A strep remains a significant cause of head and neck infections in children. PMID- 17275536 TI - Pediatric retropharyngeal lymphadenitis: differentiation from retropharyngeal abscess and treatment implications. AB - OBJECTIVES: Our objectives were to review the retropharyngeal anatomy, define retropharyngeal adenitis and abscess, and determine if CT may guide the clinician in treatment planning for pediatric retropharyngeal infections. STUDY DESIGN AND SETTING: A retrospective chart review and CT scan review of 30 children with retropharyngeal infections. RESULTS: All patients had retropharyngeal adenitis. Average volume of the low-attenuation focus in the medical treatment group was 1.2 cm3. Average volume in the surgical group was 4 cm3. Surgery patients with no purulent findings were then grouped with the medical treatment group; the average volume of the low-attenuation focus in this group was 2.2 cm3. Average volume in the group in which purulence was identified was 4.4 cm3. CONCLUSION: CT can identify patients with retropharyngeal infections who have a high likelihood of being successfully treated with antibiotics alone. SIGNIFICANCE: CT imaging may assist in avoiding unnecessary surgical exploration. PMID- 17275537 TI - Tympanometric volume: a predictor of success of tympanoplasty in children. AB - OBJECTIVES: To determine if preoperative tympanometric volumes have any predictive value in the success of pediatric tympanoplasty. STUDY DESIGN AND SETTING: Retrospective chart review in a tertiary referral center. MAIN OUTCOME MEASURES: Success was defined as no evidence of tympanic membrane perforation via otoscopic examination and normal aeration of the middle ear. METHODS: Fifty-eight pediatric patients who underwent tympanoplasty between 1996 and 2004 were studied; reviewed factors included recent discharge from the ear, perforation size, disease of the contralateral ear, age, gender, middle ear findings, and location of perforation. RESULTS: The overall success rate was 59 percent. The success rate was 89 percent for patients with a large preoperative tympanometric volume compared with 34 percent for patients with a small volume. Multivariate analysis demonstrated that disease of the contralateral ear and a large tympanometric volume were statistically significant. CONCLUSION AND SIGNIFICANCE: A large tympanometric volume may be an important factor when considering tympanoplasty in children. In addition, disease of the contralateral ear may be a prognostic indicator. PMID- 17275538 TI - A grading scale for pediatric vocal fold nodules. AB - OBJECTIVE: To design a grading scale for vocal fold nodules in pediatric patients. STUDY DESIGN AND SETTING: We conducted a prospective study in which a grading scale for vocal nodule size and contour based on static fiberoptic images of pediatric larynges was developed to achieve the scale presented here. RESULTS: Twenty-eight health care professionals each rated 28 images of pediatric vocal fold nodules. The intraclass correlation for nodule size was strong (0.77; 95% confidence interval, 0.67-0.87). The kappa statistic for nodule contour was mild (0.35; 95% confidence interval, 0.33-0.37). Agreement between experienced and other raters found no significant difference for the nodule size or contour grade of a given image. CONCLUSIONS: A grading scale for pediatric vocal fold nodules is presented. Interrater reliability for nodule size is high and can be reliably used by health care professionals with varying levels of experience. SIGNIFICANCE: A validated grading scale facilitates objective analysis of outcomes when studying and following patients with vocal nodules. PMID- 17275539 TI - Vocal fold augmentation with calcium hydroxylapatite (CaHA). AB - OBJECTIVES: Evaluate the effectiveness of CaHA injection for patients with glottal incompetence. METHODS: Multi-center, open-label, prospective clinical study with each patient serving as his/her own control. Voice-related outcome measures were collected for pre-injection and 1, 3, and 6 months. RESULTS: Sixty eight patients were available for evaluation. Fifty percent of the injection procedures were done in office. Fifty-seven percent were diagnosed with unilateral paralysis and 42% with glottal incompetence with mobile vocal folds. Patient satisfaction 6 months post showed 56% had significantly improved voice and 38% reported moderately improved voice. Paired t tests from baseline to 6 months showed significant improvements on the VHI and VAS (vocal effort), CAPE-V judgments of voice severity and videoendostroboscopy ratings of glottal closure, and objective voice measures of glottal closure (MPT and S:Z ratio). CONCLUSIONS: Preliminary results in this large cohort of patients demonstrate excellent clinical results. PMID- 17275540 TI - Efficacy of once-daily esomeprazole treatment in patients with laryngopharyngeal reflux evaluated by 24-hour pH monitoring. AB - OBJECTIVE: Laryngopharyngeal reflux (LPR) is generally treated with twice-daily proton-pump inhibitor (PPI) therapy. In this study, the efficacy of esomeprazole 40 mg once-daily together with lifestyle modifications was determined by repeated 24-hour pH monitoring. STUDY DESIGN AND SETTING: A prospective study. Forty-nine patients with suspected LPR underwent 24-hour pH monitoring. Twenty-seven of 49 patients with measurable abnormal proximal reflux reflected by a reflux area index (RAI)>6.3 were treated with esomeprazole 40 mg every day, and a second pH study was performed. RESULTS: In 22 of 27 patients, everyday PPI treatment reduced the RAI. Four of 5 patients with no RAI reduction reported on symptomatic relief. CONCLUSION: In a considerable number of patients with suspected LPR, pH monitoring reveals no abnormal proximal reflux. Esomeprazole 40 mg every day together with lifestyle modifications could reach adequate acid suppression in a large number of patients. Symptom improvement is also reported by patients without measurable effects of therapy. PMID- 17275541 TI - Current diagnosis and treatment of laryngocele in adults. AB - OBJECTIVE: To evaluate the treatment outcome of a series of laryngoceles and to comment on the current diagnosis and management of laryngoceles. STUDY DESIGN AND SETTING: A retrospective review of charts, radiological and histopathological notes, videolaryngostroboscopic records, and acoustic voice analyses of patients with laryngocele treated over a 10-year period was undertaken. RESULTS: Seven patients had internal laryngoceles; one had external; another one had combined laryngocele. Patients with internal laryngocele underwent endoscopic CO2 laser resection, while those with external or combined laryngocele were treated via external approach. Quality of voice was improved and no recurrences were encountered during the follow-up. No evidence of laryngeal cancer was found on the histological examinations. CONCLUSION: Endoscopic CO2 laser resection of internal laryngocele provides a reliable and cost-effective method that minimizes hospitalization and the need for tracheotomy. We believe that advances in the applications of laser in microlaryngosurgery will alter the traditional management of all type of laryngoceles. PMID- 17275542 TI - Hydrogen peroxide ototoxicity in unblocking ventilation tubes: a chinchilla pilot study. AB - OBJECTIVE: Some clinicians use hydrogen peroxide (H2O2) to clear the lumen of ventilation tubes that become blocked postoperatively. The ototoxicity associated with H2O2 has been controversial. STUDY DESIGN: We designed an experiment to test if H2O2 damages the cochlear hair cells using a Chinchilla laniger animal model. METHODS: Nine chinchillas (18 ears) were included in this study. Each animal was used as its own control. Following the insertion of ventilation tubes in both ears and baseline recordings of the auditory brain stem responses (ABR), we instilled 2 ml of 3 percent H2O2 into their right external auditory canals (experimental ears). H2O2 was left in the external auditory canal for a total of 5 minutes and then was drained. We instilled a normal saline control solution in their left ears (control ears) in a similar fashion. ABR recordings were performed 1 day after the last instillation of H2O2 and 5 days later. RESULTS: There was no statistically significant difference in the ABR thresholds of the experimental and control ears. CONCLUSION: H2O2 did not appear to cause ototoxicity in chinchilla ears with tympanostomy tubes exposed to H2O2 instillation using a standard clinical protocol. PMID- 17275543 TI - Hearing outcome of sudden sensorineural hearing loss: long-term follow-up. AB - OBJECTIVE: To evaluate the time-dependent progress and delayed improvement in patients who were treated with combination therapy including oral corticosteroid for idiopathic sudden sensorineural hearing loss. STUDY DESIGN AND SETTING: This retrospective study at a secondary referral and university-based center included 156 patients who were treated by 10-day course of admission therapy and followed for at least three months. RESULTS: Of 121 patients who recovered over three months of follow-up, 45.5% showed a delayed recovery after the end of 10-day course of therapy. Of these 55 patients, 78.2% recovered within one month, 5.5% recovered within one to two months, 12.7% recovered in two to three months, and 3.6% recovered later than three months after discharge. CONCLUSIONS: This study describes the long-term results for a three-month retrospective series of 156 patients diagnosed with idiopathic sudden sensorineural hearing loss, although this result should be further studied by additional research. PMID- 17275544 TI - Neuroprotective effects of TJ-23 (Tokishakuyakusan) on adult rat motoneurons following peripheral facial nerve axotomy. AB - OBJECTIVE: We investigated free radical scavenging activity and the possible neuroprotective effect of Tokishakuyakusan (TJ-23) on facial motor nucleus (FMN) motoneurons after peripheral axotomy. STUDY DESIGN: In 40 adult rats, the right facial nerve was transected at the level of the stylomastoid foramen. Following axotomy, the effects of TJ-23 on nitric oxide synthase were investigated using NADPH-d histochemistry. FMN motoneurons were counted bilaterally in sections stained with cresyl violet. RESULTS: Rats administered TJ-23 exhibited clear suppression of injury-induced neuronal NADPH-d expression in the ipsilateral FMN when compared to nontreated controls. The number of surviving motoneurons in the ipsilateral FMN was significantly greater among TJ-23-treated rats than nontreated controls on day 56 following axotomy. CONCLUSION: The present study demonstrates the neuroprotective effect of TJ-23 after peripheral facial nerve axotomy. SIGNIFICANCE: Antioxidants may have therapeutic potential in traumatic facial nerve dysfunction resulting from head injury, ear surgery, and parotid gland surgery. PMID- 17275545 TI - A mandibular advancement device for the ENT office to treat obstructive sleep apnea. AB - OBJECTIVE: To prospectively evaluate the efficacy of the mandibular advancement device (MAD) Somnoguard in the treatment of OSA patients. STUDY DESIGN AND SETTING: Forty-four patients with OSA and noncompliant to continuous positive airway pressure were enrolled in this case series. Somnoguard is made of thermoplastic material. Direct intraoral fitting was done by an otorhinolaryngologist. Polysomnographic data concerning sleep and respiration were assessed at baseline and after familiarization with the MAD. RESULTS: Sleep efficiency and sleep stages distribution did not change significantly. The RDI could be reduced from 31.5+/-17.6 to 18.2+/-17.0 (P<0.05), the minimal oxygen saturation increased from 78+/-12.9 to 82+/-12.5% (P<0.05). According to standard criteria, 18 patients were cured, 12 were improved, 8 remained unchanged, and 6 worsened. Snoring time decreased from 223+/-132 to 183+/-134 minutes (P<0.05). CONCLUSION AND SIGNIFICANCE: With Somnoguard 68% of the enrolled OSA patients could be cured or substantially improved. It is a simple MAD for the otolaryngologist. PMID- 17275546 TI - Treatment compliance in patients lost to follow-up after polysomnography. AB - OBJECTIVES: Studies on positive airway pressure (PAP) compliance typically focus only on patients who returned for follow-up. In this study, we examined patients who failed to follow-up after their initial polysomnogram (PSG) and PAP titration to determine their treatment status in terms of PAP usage. STUDY DESIGN: On retrospective chart review, we identified 57 patients who, based on PSG findings and symptoms, required the use of PAP but failed to follow-up after titration. Twenty-five of these patients were successfully contacted and agreed to an interview. RESULTS: Only 7 (28%) patients were using PAP on a regular basis. The remaining 18 (72%) patients were noncompliant. CONCLUSIONS: A significant proportion (24%) of OSA patients who required treatment with PAP were lost to follow-up after polysomnography. This group of patients has previously been ignored in the literature. We showed in this study that majority (72%) of these patients were not being treated adequately for OSA. PMID- 17275547 TI - Clinical significance of SNAP somnography test acoustic recording. AB - OBJECTIVE: To examine the clinical significance of acoustic data recorded by the SNAP home polysomnography system (SNAP Laboratories, Glenview, IL). STUDY DESIGN AND SETTING: Retrospective analysis of SNAP data from 59 patients undergoing evaluation for sleep apnea at the University of Nebraska Medical Center and an associated private practice in Omaha, NE. RESULTS: Snoring did not correlate with anthropometric variables such as body mass index and neck circumference. Statistical analysis showed no correlation between respiratory disturbance index and the maximum or average loudness of snoring. Average loudness was predictive of the presence of sleep apnea. Spectral analysis of snoring sonography found that the proportion of snoring events associated with a palatal source correlated strongly with the loudness of snoring. CONCLUSION: These data suggest that analysis of snoring has limited utility in the evaluation of the patient with sleep apnea but may be able to select patients who would benefit from palatal procedures to reduce snoring. PMID- 17275548 TI - Intranasal CpG DNA therapy during allergen exposure in allergic rhinitis. AB - OBJECTIVE: 1) To estimate the effectiveness of intranasal administration of CpG DNA alone on allergic rhinitis compared with intradermal administration; and 2) to find out how CpG DNA therapy is useful in treatment of allergic rhinitis. STUDY DESIGN: Mice were intraperitoneally sensitized and intranasally challenged with Japanese cedar. Therapy with CpG DNA alone was also performed during challenge, either intranasally or intradermally. Immunologic variables and nasal symptom were studied. RESULTS: Intranasal administration of CpG DNA alone significantly reduced the levels of IgE, IL-5 productions from nasal lymphocytes and splenocytes, nasal eosinophilia, and nasal symptoms, although intradermal administration of CpG DNA alone showed no significant reduction. CONCLUSION: This study demonstrated that CpG DNA has effects not only on splenocytes but also on nasal lymphocytes to attenuate allergic rhinitis, and that intranasal administration, but not intradermal administration, of CpG DNA alone during allergen exposure is useful for control of allergic rhinitis. PMID- 17275549 TI - Systemic corticosteroids for allergic fungal rhinosinusitis and chronic rhinosinusitis with nasal polyposis: a comparative study. AB - OBJECTIVES: To compare the effect of preoperative high-dose systemic corticosteroids on the radiographic and endoscopic appearance of allergic fungal rhinosinusitis (AFRS) and chronic rhinosinusitis with nasal polyposis (CRSwNP). STUDY DESIGN AND SETTING: Eight AFRS and 10 CRSwNP patients underwent computed tomographic (CT) scans and then received preoperative 1 mg/kg prednisone for 10 days. CT scans were repeated 1 day before surgery and compared with pretreatment scans (Lund-MacKay radiologic scoring system). The endoscopic appearance was recorded intraoperatively. RESULTS: The score dropped from 16 (66.4%) to 4.75 in the AFRS group and from 18.4 (23%) to 14.1 in the CRSwNP group (P=0.0064). Intraoperatively, most sinus mucosal surfaces appeared normal in the AFRS patients but were markedly edematous in the CRSwNP patients. CONCLUSION: Radiographic response of AFRS to systemic corticosteroids is significantly greater compared with CRSwNP. This finding is supported by endoscopic observation. PMID- 17275550 TI - Guidelines for management of acute bacterial rhinosinusitis: impact on Quebec physicians' prescriptions for antibiotics. AB - OBJECTIVE: To determine the impact of widely distributed guidelines on the diagnosis and treatment of acute bacterial rhinosinusitis (ABRS) on physician prescribing patterns. STUDY DESIGN AND SETTING: The overall numbers of prescriptions were compared between Quebec and the rest of Canada (excluding Quebec) using IMS Health Canada Canadian Disease and Therapeutic Index and CompuScript data on the antibiotics use for ABRS for the 3-month period immediately following the distribution of the guidelines and the corresponding period the previous year. RESULTS: In comparison to the corresponding period during the previous year, antibiotic prescriptions for ABRS decreased 5.5% overall in Quebec compared with a 30.1% increase recorded in Canada excluding Quebec. CONCLUSION: While the reduction in antibiotics use noted may be multifactorial, it nevertheless suggests that it may be able to affect physician prescribing habits. SIGNIFICANCE: Knowledge of the effectiveness of this method of distribution of guidelines could be used to plan more effective means of distribution of future guidelines. PMID- 17275551 TI - Radical surgery: effect on quality of life and pain in chronic rhinosinusitis. AB - OBJECTIVES: Despite effective medical therapy and repetitive endoscopic sinus surgery in the treatment of chronic rhinosinusitis, there still remains a small group of patients without improvement of symptoms. This study evaluates the effect of radical surgery on quality of life and pain in these patients with recalcitrant disease. STUDY DESIGN: A prospective, questionnaire-based study was conducted in 23 patients who underwent Denker's procedure for refractory chronic rhinosinusitis. Quality of life and pain were evaluated before surgery and 12 months and 2 years after surgery with the SF-36 and McGill Pain Questionnaire. RESULTS: Seven of the eight mean scores of the SF-36 postoperatively improved after surgery, with statistical significance for Role Physical (RP) P=0.048. Bodily pain showed a strong tendency to significance. Results of the McGill Pain Questionnaire show a significant improvement in most of the subscores after surgery implying less pain. CONCLUSION: Radical surgery improves the physical burden of chronic rhinosinusitis and pain experience in patients with therapy resistant chronic rhinosinusitis. PMID- 17275552 TI - Feasibility of near real-time image-guided sinus surgery using intraoperative fluoroscopic computed axial tomography. AB - OBJECTIVE: One of the main limitations of image-guided surgery is that navigation relies on the use of a CT scan obtained before surgery and is unable to be updated during the procedure. A software addition has been developed to allow reconstruction of CT-like images from a series of fluoroscopic scans and integrate these into an image-guided system (GE Healthcare Surgical Navigation, Lawrence, MA). We report our initial experience with a series of patients undergoing intraoperative fluoroscopic navigation in sinus surgery. STUDY DESIGN AND SETTINGS: After institutional review board clearance, we prospectively studied 14 consecutive patients undergoing image-guided sinus surgery with the use of intraoperative fluoroscopy. RESULTS: All patients had preoperative and postoperative fluoroscopic images reconstructed into CT-like images. By the conclusion of the study, images were adequate in quality and accurate navigation was achieved. CONCLUSION: Real-time image-guided sinus surgery using fluoroscopy is feasible. Future studies will need to focus on defining the procedures that could benefit, such as tumor resection, to enhance patient safety during these operations. PMID- 17275553 TI - Efficacy of dexamethasone for reducing postoperative nausea and vomiting and analgesic requirements after thyroidectomy. AB - OBJECTIVE: To evaluate the efficacy of dexamethasone for reducing postoperative nausea and vomiting (PONV) and analgesic requirements after thyroidectomy. STUDY DESIGN AND SETTING: In a prospective, randomized, double-blind, placebo controlled study, 75 patients, 20 men and 55 women, received intravenously placebo or dexamethasone at 2 different doses (4 and 8 mg) (n=25 of each) at the end of surgery. A standard general anesthetic technique was used. PONV and analgesic requirements were evaluated. RESULTS: The rate of patients experiencing PONV during the first 24 hours after anesthesia was 64% with dexamethasone 4 mg (P=0.269) and 28% with dexamethasone 8 mg (P=0.001), compared with placebo (76%). The need of indomethacin for intolerable pain was less in patients who had received dexamethasone 8 mg than in those who had received placebo (P=0.009). CONCLUSION: Dexamethasone 8 mg effectively decreases PONV and analgesic requirements after thyroidectomy. PMID- 17275554 TI - Total thyroidectomy is the preferred treatment for patients with Graves' disease and a thyroid nodule. AB - OBJECTIVE: To identify the indications and outcomes of total thyroidectomy for Graves' disease in a North American cohort. STUDY DESIGN AND SETTING: Prospective database of 297 patients undergoing total thyroidectomy in a tertiary care center identified 49 patients with Graves'. RESULTS: There were 37 women and 12 men (mean age, 37.9 years). Common indications for surgery were: refusal of radioactive iodine (20%), thyroid storm (18%), a thyroid nodule (16%), failure of I131(14%), and ophthalmopathy (14%). Complications included: symptomatic hypocalcemia (14%), permanent hypoparathyroidism (0%), and symptoms of recurrent laryngeal nerve injury (0%). Graves' patients had more bleeding (117 mL versus 48 mL, P<0.05). Clinical nodules were malignant in 38%. Papillary thyroid carcinoma occurred in 10% of patients, with 60% multifocal, and 60% lymph node metastases. CONCLUSION: Total thyroidectomy for Graves' has minimal morbidity. Patients with Graves' and a thyroid nodule are at an increased risk for malignancy and should be treated with a total thyroidectomy. PMID- 17275555 TI - Outpatient parathyroid surgery and the differences seen in the morbidly obese. AB - OBJECTIVE: This prospective study examined rapid patient discharge after routine parathyroidectomy to identify differences between morbidly obese and non-morbidly obese patients. The efficacy of supplemental calcium in preventing postoperative hypocalcemia was also assessed. METHODS: Between March 2003 and June 2004, 842 patients with primary hyperparathyroidism underwent outpatient parathyroid surgery. Morbid obesity was defined as 100 pounds above ideal body weight and/or body mass index greater than 39. RESULTS: Fifty-one (6.1%) patients were morbidly obese (mean, 261 lbs; body mass index=45) compared with 791 non-morbidly obese patients (mean, 172 lbs; body mass index=28, P<.001). Morbidly obese patients were more likely to require conversion of laryngeal masked airway to endotracheal intubation (P<.05). Incision length, total operative times, and the total time spent in the post-anesthesia care unit were longer for morbidly obese patients (all, P<.05). Of the 842 patients, only four, all non-morbidly obese, spent the night after their operation. No postoperative untoward events occurred in either group. CONCLUSIONS: Immediate discharge after routine parathyroid surgery is extremely safe for nearly all patients although morbid obesity is associated with a longer operation, a more difficult airway, and a longer stay in the recovery room. PMID- 17275556 TI - Is routine inclusion of level IV necessary in neck dissection for clinically N0 supraglottic carcinoma? AB - OBJECTIVE: Elective level II to IV dissection has become a common practice for patients with N0 neck and supraglottic laryngeal carcinoma. Several authors have questioned the necessity of dissecting level IV and the possible risk of associated morbidities such as chyle leak and phrenic nerve injury. STUDY DESIGN AND SETTING: We reviewed 58 patients who underwent elective functional and lateral neck dissection for supraglottic carcinoma. Node levels were delineated just after the removal of the specimens. The patients were followed at least 3 years postoperatively or until the time of death; recurrence rates and levels were evaluated. RESULTS: Occult lymph node metastases were determined in 14 cases. Level II was the most involved zone (7 patients). Isolated level IV lymph node metastasis was not established. CONCLUSION: We think that routine level IV dissection is not necessary in the management of clinically and radiologically N0 necks in patients with supraglottic laryngeal carcinoma. PMID- 17275557 TI - A clinico-pathological study of laryngeal and hypopharyngeal carcinoma: correlation of cord-arytenoid mobility with histopathologic involvement. AB - OBJECTIVE: This study evaluates the vocal cord and arytenoid mobility in relation to the tumoral involvement of the cricoarytenoid joint (CAJ), thyroarytenoid (TA) muscle, and posterior cricoarytenoid (PCA) muscle in whole-organ sections of total laryngectomy specimens. STUDY DESIGN AND SETTING: The study was prospectively carried out between 1998 and 2003 and involved 133 primary squamous cell carcinoma cases of larynx or pyriform sinus that were treated with total laryngectomy. Preoperative mobility of vocal cords and arytenoids were evaluated separately and correlated with histopathologic findings. RESULTS: In cases with fixed vocal cord CAJ, TA muscle, and PCA muscle were involved in 42.4%, 72.9%, and 27.1% of the cases, respectively, while in cases with fixed arytenoid these structures were affected in 40%, 66.3%, and 25.3% of the cases. Weight effect seemed to play a role in 60% and 50% of the cases of supraglottic and pyriform sinus carcinoma, respectively. CONCLUSION: Careful evaluation of the mobility of the cord arytenoid unit separately helps the surgeon to better understand the patterns of tumoral extension guiding for the appropriate surgery which should be undertaken. PMID- 17275558 TI - Total laryngectomy and T3-T4 laryngeal cancer without other adverse histopathology. AB - OBJECTIVE: We sought to determine the postoperative management, incidence of tumor recurrence in the neck, and outcome in laryngeal cancer patients whose risk for tumor relapse is not clear. STUDY DESIGN AND SETTING: Thirty patients (27 of whom had transglottic tumors) met the study criteria (resected T3-T4 laryngeal cancer, histologically negative cervical nodes, and no other adverse histopathology). A group of 12 patients who underwent surgery alone was compared with a second group of 18 patients with similar characteristics but who received postoperative radiotherapy. RESULTS: Overall survival at five years was 50% in the surgery alone group and 61% in the combined therapy group (P=0.63). Among the 28 evaluable patients with a median follow-up of 44 months, the relapse rate in the neck was 25% in the surgery alone group and was 0% in the postoperatively irradiated group (P=0.07). Recurrences in the neck remained uncontrolled in two of the three patients at the time of death. CONCLUSION AND SIGNIFICANCE: Postoperative radiotherapy deserves consideration in selected cases of T3-T4 laryngeal cancer without adverse histopathology. PMID- 17275559 TI - Adult outpatient tracheostomy care: practices and perspectives. AB - OBJECTIVES: To determine the attitudes, opinions, and current practice of adult outpatient tracheostomy care from the surgeon and primary care physician's perspective. STUDY DESIGN: Multidisciplinary physician survey. RESULTS: Found 53.4% (667 of 1250) and 28.9% (404 of 1400) of otolaryngologists and internists responded, respectively; 47% of otolaryngologists lack standardized tracheostomy discharge protocols. General ward nurses most commonly (33%) provide discharge education. A total of 64% of otolaryngologists felt primarily responsible for tracheostomy care and follow-up; 48% expect the primary physician to provide some or all tracheostomy care. Ninety-seven percent of internists received little or no residency training in tracheostomy care, which was significantly associated with decreased comfort (P<0.0001) and willingness (P<0.0001) to care for these patients. CONCLUSIONS: Tracheostomy care is a concerted effort between the patient, surgeon, primary physician, and interdisciplinary team. Otolaryngologists should strive to standardize tracheostomy discharge, education, and follow-up practices. SIGNIFICANCE: Disparities are highlighted between disciplines in their comfort, willingness, and knowledge of outpatient tracheostomy care. PMID- 17275560 TI - GlideScope video laryngoscopes. PMID- 17275561 TI - An augmented liberatory maneuver for benign paroxysmal positional vertigo for patients who are difficult to move. PMID- 17275562 TI - Bifurcate horn on the tip of the nose. PMID- 17275563 TI - Hutchinson sign and herpes zoster. PMID- 17275564 TI - Glossal vascular leiomyoma. PMID- 17275565 TI - Acute airway obstruction from a thyroglossal duct cyst. PMID- 17275566 TI - Extranasal glial heterotopia: an unusual cause of a lateral neck mass in a child. PMID- 17275567 TI - Unusual malignant transformation of juvenile recurrent respiratory papillomatosis. PMID- 17275568 TI - Spontaneous expulsion of a bronchial foreign body. PMID- 17275569 TI - Successful replantation of an amputated nose after dog bite injury. PMID- 17275570 TI - Pleomorphic adenoma of the palpebral lobe of the lacrimal gland. PMID- 17275571 TI - Small cell carcinoma of the parotid gland. PMID- 17275572 TI - Malignant melanoma of infratemporal fossa. PMID- 17275574 TI - The role of gastric Helicobacter pylori infection in laryngopharyngeal reflux disease. PMID- 17275575 TI - Reply to: coblation lingual tonsillectomy. PMID- 17275578 TI - Metabolic alkalosis, bedside and bench. AB - Although significant contributions to the understanding of metabolic alkalosis have been made recently, much of our knowledge rests on data from clearance studies performed in humans and animals many years ago. This article reviews the contributions of these studies, as well as more recent work relating to the control of renal acid-base transport by mineralocorticoid hormones, angiotensin, endothelin, nitric oxide, and potassium balance. Finally, clinical aspects of metabolic alkalosis are considered. PMID- 17275579 TI - Inherited renal tubulopathies associated with metabolic alkalosis: effects on blood pressure. AB - Inherited tubular disorders associated with metabolic alkalosis are caused by several gene mutations encoding different tubular transporters responsible for NaCl renal handling. Body volume and renin-angiotensin-aldosterone system status are determined by NaCl reabsorption in the distal nephron. Two common hallmarks in affected individuals: hypokalemia and normal / high blood pressure, support the differential diagnosis. Bartter's syndrome, characterized by hypokalemia and normal blood pressure, is a heterogenic disease caused by the loss of function of SLC12A1 (type 1), KCNJ1 (type 2), CLCNKB (type 3), or BSND genes (type 4). As a result, patients present with renal salt wasting and hypercalciuria. Gitelman's syndrome is caused by the loss of funcion of the SLC12A3 gene and may resemble Bartter's syndrome, though is associated with the very low urinary calcium. Liddle's syndrome, also with similar phenotype but with hypertension, is produced by the gain of function of the SNCC1B or SNCC1G genes, and must be distinguished from other entities of inherited hypertension such as Apparently Mineralocorticoid Excess, of glucocorticoid remediable hypertension. PMID- 17275580 TI - Mineralocorticoid hypertension and hypokalemia. AB - Mineralocorticoid hypertension is hypertension associated with the presence of hypokalemia, metabolic alkalosis, and suppression of plasma renin. Mineralocorticoid hypertension represents only 10% of patients with essential hypertension. However, its recognition is important because it is a potentially reversible cause of hypertension. Primary hyperaldosteronism is the most common form of mineralocorticoid hypertension. It is current clinical practice to use the plasma aldosterone-renin ratio and the absolute plasma aldosterone level as screening tests. Confirmatory suppression tests and adrenal imaging are performed in appropriate patients. Three monogenic forms of mineralocorticoid hypertension have been identified including Liddle's syndrome, glucocorticoid-remediable hypertension, and apparent mineralocorticoid excess. In a number of patients with mineralocorticoid hypertension, hypokalemia can be a variable finding. This review highlights mineralocorticoid biology and important features of primary hyperaldosteronism and monogenic hypertension. PMID- 17275581 TI - Physiology of acid-base balance: links with kidney stone prevention. AB - Two processes permit the urine pH and the medullary interstitial pH to remain in an "ideal range" to minimize the risk of forming kidney stones. First, a medullary shunt for NH(3) maintains the urine pH near 6.0 to minimize uric acid precipitation when distal H(+) secretion is high. Second, excreting dietary alkali excreting alkali as a family of organic anions--including citrate--rather than as bicarbonate maintains the urine pH near 6.0 while urinary citrate chelates ionized calcium, which minimizes CaHPO(4) precipitation. In patients with idiopathic hypercalciuria and recurrent calcium oxalate stones, the initial nidus is a calcium phosphate precipitate on the basolateral membrane of the thin limb of the loop of Henle (Randall's plaque). Formation of this precipitate requires medullary alkalinization; K(+) -depletion and augmented medullary H(+)/K(+) -ATPase may be predisposing factors. PMID- 17275582 TI - The evolution-informed optimal dietary potassium intake of human beings greatly exceeds current and recommended intakes. AB - An organism best fits the environment described by its genes, an environment that prevailed during the time period (millions of years) when evolution naturally selected the genes of its ancestors-those who survived to pass on their genes. When an organism's current environment differs from its ancestral one, the environment's mismatch with the organism's genome may result in functional disadvantages for the organism. The genetically conditioned nutritional requirements of human beings established themselves over millions of years in which ancestral hominins, living as hunter-gatherers, ate a diet markedly different from that of agriculturally dependent contemporary human beings. In that context, we sought to quantify the ancestral-contemporary dietary difference with respect to the supply of one of the body's major mineral nutrients: potassium. In 159 retrojected Stone Age diets, human potassium intake averaged 400 +/- 125 mEq/d, which exceeds current and recommended intakes by more than a factor of 4. We accounted for the transition to the relatively potassium-poor modern diet by the fact that the modern diet has substantially replaced Stone Age amounts of potassium-rich plant foods (especially fruits, leafy greens, vegetable fruits, roots, and tubers), with energy-dense nutrient-poor foods (separated fats, oils, refined sugars, and refined grains), and with potassium-poor energy rich plant foods (especially cereal grains) introduced by agriculture (circa 10,000 years ago). Given the fundamental physiologic importance of potassium, such a large magnitude of change in potassium intake invites the consideration in human beings of whether the quantitative values of potassium-influenced physiologic phenomena (eg, blood pressure, insulin and aldosterone secretion rates, and intracellular pH) currently viewed as normal, in fact disaccord with genetically conditioned norms. We discuss the potential implications of our findings in respect to human health and disease. PMID- 17275583 TI - Interrelationships among hypoxia-inducible factor biology and acid-base equilibrium. AB - In this article, we try to summarize the most important novel biological information on the complex interrelationships between acid-base alterations and hypoxia-inducible factor (HIF) signaling. Extracellular and intracellular acid base alterations affect HIF signaling in part independently of hypoxia, and involve, among others, effects on cytoprotection and apoptosis. Conversely, HIF signaling may affect systemic and local acid production rates and has been implicated in the mechanism of the acute hyperventilatory response (ie, respiratory alkalosis) in response to hypoxia as well as for hypoxia-induced pulmonary artery hypertension (PAH), although the latter data are quite preliminary and can be explained by alternative mechanisms. Thus, this review calls attention to these relationships for renal physiologists and nephrologists to stimulate focused clinical observations and specific investigative efforts as proposed in this overview. PMID- 17275584 TI - Acid-base and potassium disorders in liver disease. AB - Acid-base and potassium disorders occur frequently in the setting of liver disease. As the liver's metabolic function worsens, particularly in the setting of renal dysfunction, hemodynamic compromise, and hepatic encephalopathy, acid base disorders ensue. The most common acid-base disorder is respiratory alkalosis. Metabolic acidosis alone or in combination with respiratory alkalosis also is common. Acid-base disorders in patients with liver disease are complex. The urine anion gap may help to distinguish between chronic respiratory alkalosis and hyperchloremic metabolic acidosis when a blood gas is not available. A negative urine anion gap helps to rule out chronic respiratory alkalosis. In this disorder a positive urine anion gap is expected owing to suppressed urinary acidification. Distal renal tubular acidosis occurs in autoimmune liver disease such as primary biliary cirrhosis, but often is a functional defect from impaired distal sodium delivery. Potassium disorders are often the result of the therapies used to treat advanced liver disease. PMID- 17275585 TI - Distal renal tubular acidosis and the potassium enigma. AB - Severe hypokalemia is a central feature of the classic type of distal renal tubular acidosis (RTA), both in hereditary and acquired forms. In the past decade, many of the genetic defects associated with the hereditary types of distal RTA have been identified and have been the subject of a number of reviews. These genetic advances have expanded our understanding of the molecular mechanisms that lead to distal RTA. In this article, we review data published in the literature on plasma potassium from patients with inherited forms of distal RTA. The degree of hypokalemia varies depending on whether the disease is autosomal autosomal-recessive or dominant, but, interestingly, it occurs in defects caused by mutations in genes encoding the AE-1 exchanger, the carbonic anhydrase II gene, and genes encoding different subunits of the H+ adenosine triphosphatase. This shows that a unique defect involving the H+/K+-adenosine triphosphatase leading to renal potassium wastage cannot explain the hypokalemia seen in virtually all types of classic distal RTA. PMID- 17275586 TI - Critical reappraisal of Medical Research Council muscle testing for elbow flexion. AB - PURPOSE: To critically evaluate the current standard for manually assessing strength both clinically and in the scientific literature: the 0-to-5 scale that evolved from the post-World War II report of the British Medical Research Council. Although widely used by surgeons and researchers, no physical analysis of its validity is available. With the elbow used as an example, a static physics experiment is devised to quantify the enormous difference between maximum strength (grade 5/5) and the strength needed to statically flex against gravity (grade 3/5). METHODS: The weight, length, and center of gravity of 27 cadaver forearms were measured to determine the typical torque needed to flex the elbow against gravity. The result is expressed as a percentage of maximum strength, based on published data. RESULTS: Estimated elbow strength needed to flex against gravity was 4% of the maximum strength at the elbow. CONCLUSIONS: Of the 6 possible grades from 0 to 5, the single grade 4/5 represents more than 96% of potential elbow flexion strength. For elbow flexion, grade 4/5 includes both the very weak and the very strong. Grade 3/5 strength may be much weaker than is generally assumed. PMID- 17275587 TI - Use of the Medical Research Council muscle strength grading system in the upper extremity. PMID- 17275589 TI - Reconstruction of the first web space in symbrachydactyly using the reverse radial forearm flap. AB - PURPOSE: To present a new approach for the reconstruction of severe first web contractures using a distally based reverse radial forearm flap in symbrachydactyly patients. METHODS: This study included 6 hands in 5 patients. Subjective evaluation included appearance, parent satisfaction (and patient satisfaction when appropriate), and ability to perform daily activities such as thumb-index grasp and pinch at follow-up evaluations. We measured the angle between the first and second rays using a goniometer at maximum radial abduction, and pinch and grasp strengths were evaluated as an objective assessment. RESULTS: The average follow-up period was 2 years. All parents and patients were happy with the aesthetic appearance. They were completely satisfied in their daily living activities. The average first web angle measurement was 56 degrees . An average of 39 degrees of improvement of web measurement was achieved. For the unilateral 4 patients, the average pinch strength measurement was 80% of the normal contralateral hand and the grip strength was 75% of the normal contralateral hand. CONCLUSIONS: The reverse radial forearm flap was found to be a safe and simple method in the reconstruction of severe first web contractures in symbrachydactyly patients. This method provided good coverage of appropriate thickness and skin quality, and supple soft tissue that filled the first web space. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 17275588 TI - Thumb function and appearance in thrombocytopenia: absent radius syndrome. AB - PURPOSE: To evaluate thumb function and appearance in patients with thrombocytopenia absent radius (TAR) syndrome. METHODS: The size and shape of the 14 thumbs in 7 patients with TAR syndrome were quantified and compared with age matched normals. Function was assessed using a series of standardized tasks. RESULTS: The thumb length averaged 73% relative to the length of the index finger proximal phalanx (normal, 70%) and 36% relative to the length of the entire index finger (normal, 32%). The thumb/index nail width and girth ratios measured 138% and 101%, respectively (normal, 133% and 105%, respectively). The relative thumb/index thumbnail width-to-girth ratio was 1.36, which was significantly greater than the normal average of 1.27, suggesting the TAR thumbs are relatively wide and flat compared with normal thumbs. The thumb interphalangeal joint was held in a neutral posture and did not show active motion in any patient; the metacarpophalangeal joint was held in a position of flexion and had an average of 32 degrees of extension lag. Patients had difficulty with all activities tested, especially grasping large objects. CONCLUSIONS: The thumb in TAR syndrome patients is of relatively normal size and shape; however, the thumb is held in a position of metacarpophalangeal flexion in most patients and function is impaired. PMID- 17275590 TI - Congenital shortening of the flexor digitorum profundus muscle. AB - An 8-year-old boy with a history of the inability to extend the middle finger at the proximal interphalangeal and distal interphalangeal joints with the wrist and metacarpophalangeal joints in the neutral position since the age of 5 months had surgery. The flexor digitorum profundus muscle of the middle finger had a short muscle belly and was replaced in part with mature fat tissue. Histologic examination of the resected tissue showed replacement of a part of the muscle with mature fat tissue. It was speculated that some myosatellite cells, which typically differentiate into skeletal muscle cells, may have erroneously differentiated into adipocytes in the first postnatal year, during which complete development of skeletal muscles occurs. PMID- 17275591 TI - Pediatric scaphoid nonunion. AB - PURPOSE: To report the outcome of pediatric scaphoid nonunions treated with a Herbert screw and bone graft. METHODS: This is a retrospective review of 12 cases of scaphoid nonunion in 12 skeletally immature patients treated with a uniform approach consisting of open reduction, iliac crest bone grafting and Herbert screw fixation. All patients were boys and presented with nonunions of the scaphoid waist. The final follow-up evaluation was at a mean of 32 months, ranging from 22 to 45 months, and consisted of assessing anatomic snuffbox tenderness, wrist arc of motion, grip strength, calculation of the Modified Mayo Wrist score, and assessment of union based on plain radiographs. RESULTS: At the latest follow-up evaluation, all patients were pain free (including absence of snuffbox tenderness) except one who experienced slight discomfort during extreme activities. There was no statistically significant difference in the arc of motion between the surgically treated and healthy sides, and the average grip strength was 96% that of the contralateral extremity. Clinical and radiographic union was present in all cases at a mean of 3.4 months after surgery. The Modified Mayo Wrist score was excellent in 11 patients and good in 1. There were no complications. CONCLUSIONS: Open reduction and internal fixation with a Herbert screw reliably obtained union in all patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 17275592 TI - Arthroplasty of the distal radioulnar joint using a new ulnar head endoprosthesis: preliminary report. AB - PURPOSE: To report our experience using a distal ulnar head endoprosthesis to treat painful disorders of the distal radioulnar joint (DRUJ) secondary to (1) instability and (2) arthrosis. METHODS: Our experience with over 2 years of follow-up study consists of 19 wrists (17 patients). All patients presented complaining of pain and functional disability of the upper limb due to convergence instability or arthrosis of the DRUJ. The patients were studied prospectively. Thirteen patients had a total of 37 previous wrist or DRUJ surgical procedures. Standardized preoperative and postoperative assessments included a patient-reported pain score, a functional satisfaction score, forearm range of motion, grip strength as a percentage of that of the opposite limb, and clinical and radiographic examinations. The Mayo Wrist Score was calculated before surgery and at the last follow-up period. RESULTS: Overall, pain scores decreased 50%, and functional satisfaction scores improved 3-fold. Average grip strength improved by 4 kg, or 16% from preoperative measurements. Forearm rotation was unchanged. All wrists were clinically stable on the latest follow-up examination. Two failures occurred early, at 7 and 14 months. Currently, all prostheses remain clinically and radiographically stable. CONCLUSIONS: Implant arthroplasty of the distal ulna combined with an adequate soft-tissue repair is recommended to improve pain, function, and strength of the wrist and forearm. Prosthetic replacement of the distal ulna restored stability to the DRUJ in patients with partial or complete excision of the ulnar head or DRUJ arthrosis and corrected radioulnar impingement. Incidences of complications or revision surgery to date have been low. Larger clinical and radiographic assessments will be needed to determine the long-term success of distal ulna prosthetic replacement. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 17275593 TI - Oxidation of silicone elastomer finger joints. AB - PURPOSE: We analyzed the oxygen content of 19 retrieved implants and 6 packaged implants to further understand the mechanism of degradation of silicone elastomer finger joints while in vivo. METHODS: Nineteen Swanson (Wright Medical Technology, Arlington, TN) silicone elastomer finger joints were retrieved at revision surgery at an average of 7 years of use. Six packaged and expired implants (5 years after the expiration date) along with the retrieved implants were studied with an elemental analyzer for the total percentage (by weight) of oxygen content. RESULTS: The retrieved implants showed a mean total oxygen content of 0.41% +/- 0.35%, whereas each of the packaged specimens showed less than 0.1% total oxygen content. Eight of the 19 retrieved implants remained unoxidized. There was no correlation between implant fracture and the oxygen content of the retrieved implants. CONCLUSIONS: Our results suggest that silicone elastomers are oxidized in vivo. Although such oxygen embrittlement may have implications in compromising silicone elastomer material mechanics during in vivo use, our data indirectly suggests that mechanical factors also have an important role in the final fracture of the silicone elastomer implant. PMID- 17275594 TI - Biomechanical comparison of fixed-angle volar plate versus fixed-angle volar plate plus fragment-specific fixation in a cadaveric distal radius fracture model. AB - PURPOSE: To test the hypothesis that combining orthogonal fragment-specific fixation with volar fixed-angle fixation provides markedly higher interfragment stability and construct strength compared with volar fixed-angle fixation alone. METHODS: Eight matched pairs of fresh cadaveric hand and forearm specimens were potted upright in cement. Flexor and extensor tendons were isolated at insertion sites and sutured into a looped bundle for loading in flexion and extension, respectively (up to 61 N). Osteotomies to simulate an AO type C2, 3-part fracture pattern were created with a saw. One randomized specimen from each pair received a locking volar plate and a radial pin plate (VP+PP), and the other received a locking volar plate only (VP). The relative angular displacements between the radial, ulnar, and proximal fragments were obtained with a motion analysis system. After stability tests, specimens were compressed to failure in a wrist extended position on a material testing machine. Paired t tests were used to compare the interfragment displacement, construct stiffness, and strength between the 2 groups. RESULTS: Comparing fragment displacement in the VP+PP and VP groups showed that with flexion-extension and radial-ulnar deviation, distal fragment displacement was reduced to a statistically significant degree. The VP+PP group also showed higher failure strength and construct rigidity than the VP group. CONCLUSIONS: In a simulated cadaveric model of the distal radius intra-articular fracture, the combined technique of fragment-specific plating with volar fixed angle fixation alone provides superior biomechanical strength and stability over the volar fixed-angle fixation alone. PMID- 17275595 TI - Early controlled passive motion improves early fracture alignment and structural properties in a closed extra-articular metacarpal fracture in a rabbit model. AB - PURPOSE: To investigate if early controlled passive mobilization was likely to cause harm with regard to affecting the quality and rate of early fracture healing in a closed, potentially unstable, diaphyseal fracture in a rabbit model. METHODS: This was a preclinical, block-randomized, single-blind efficacy trial examining 3 time periods (baseline [day 5], day 14, day 28) and 2 treatment conditions (immobilization, passive motion). Fifty mature, female, New Zealand white rabbits were preconditioned to a non-weight-bearing brace before creating a closed third metacarpal fracture. Fractures were reduced under fluoroscopy and placed in a custom-molded fracture brace. On day 5, rabbits randomly allocated to the early passive motion protocol received twice-daily 15-minute sessions of passive digital motion combined with gentle pinch stabilization of the fracture. Outcome evaluations included lateral x-rays, peripheral quantitative computerized tomography imaging, and 4-point bending to structural failure. RESULTS: Compared with the immobilized fractures, the early controlled passive motion fractures showed significantly better gains in initial stiffness, maximum stiffness, failure load, and energy absorbed per unit area, as well as showing a significant reduction in dorsal fracture angulation. The total callus area was not significantly different between the 2 groups. CONCLUSIONS: During the initial 28 days after the fracture, in this simulated hand, closed, potentially unstable, extra-articular fracture, the early controlled passive motion protocol used in this study led to a clinical and statistical significant reduction in fracture dorsal angulation and improvement in the fracture's ability to resist and bear 4 point bending loads without increasing the total callus area. Therefore, early controlled passive mobilization after a closed, potentially unstable, diaphyseal hand fracture warrants further clinical consideration. PMID- 17275596 TI - The tibial second toe vascularized neurocutaneous free flap for major digital nerve defects. AB - PURPOSE: Most digital nerve defects can be reconstructed by means of nonvascularized nerve grafts or artificial tubes, for example. When the bed is poor, the defect is long, or there is a concomitant soft-tissue loss; however, a vascularized nerve graft may be a better option. Our purpose is to introduce a method of 1-stage reconstruction of complex neurocutaneous defects in the fingers and to report the results and clinical effectiveness at a minimum 1-year follow up period. METHODS: From 1997 to 2005 there were 6 consecutive patients who had a combined soft-tissue and digital nerve defect reconstructed by a vascularized neurocutaneous flap from the tibial (medial) side of the second toe. Three were acute and 3 were chronic cases. One flap was used for the ulnar side of the thumb, 2 for the radial aspect of the index finger, 1 for the radial of the small finger, and 2 for the ulnar side of the small finger. The nerve gap averaged 4.2 cm, and the flap size averaged 3.2 x 2.1 cm. The flaps were revascularized with standard microsurgical techniques to local vessels in the fingers. The nerves were sutured with epineural stitches. A split-thickness skin graft was used to close the donor site of the toe. RESULTS: All flaps survived without complications. At the latest follow-up evaluation static two-point discrimination (s2PD) averaged 8 mm on the pulp. Three patients had normal sensation when tested with Semmes-Weinstein filaments. Subjective feeling was 78% of that of the normal side. Five patients rated their feeling as excellent on a subjective scale. The Disabilities of the Arm, Shoulder, and Hand questionnaire score averaged 5. CONCLUSIONS: The tibial neurocutaneous second toe free flap is suitable for reconstructing a missing nerve and soft-tissue defect in the finger. We found good functional recovery and high satisfaction in this group of patients. The donor site morbidity has been minimal, although delayed healing is common. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 17275597 TI - Nerve transfer to deltoid muscle using the intercostal nerves through the posterior approach: an anatomic study and two case reports. AB - PURPOSE: To evaluate the feasibility of restoring the deltoid function in patients with C5 through C7 root avulsion injuries by transferring 2 intercostal nerves to the anterior branch of the axillary nerve through a posterior approach. The preliminary results of the clinical application of this procedure also are reported. METHODS: The study was performed on 10 fresh cadavers. The lengths of the third, fourth, and fifth intercostal nerves from the costochondral junction to the midaxillary line were recorded. The distance from the pivot point at the midaxillary line to the anterior branch of the axillary nerve was recorded as the tunnel length. All histomorphometric measurements of the axon number were recorded. Based on the anatomic study, the fourth and fifth intercostal nerves were transferred directly to the anterior branch of the axillary nerve in 2 patients. RESULTS: The average distances from the costochondral junction of the third, fourth, and fifth intercostal nerves to the pivot points were 12, 15, and 16 cm, respectively. The average tunnel distances of the third, fourth, and fifth intercostal nerves were 11, 13, and 15 cm, respectively. The average numbers of myelinated nerve fibers of the third, fourth, and fifth intercostal nerves were 742, 830, and 1,353, respectively. At the 2-year follow-up evaluation the preliminary clinical results showed that the deltoid recovered against resistance (M4). The range of motion for shoulder abduction and external rotation were both 95 degrees in the first case and 105 degrees and 95 degrees , respectively, in the second case. Useful functional recovery was achieved and classified as a good result in both patients. CONCLUSIONS: This anatomic study with 2 case reports supports the idea that transfer of 2 intercostal nerves to the anterior branch of the axillary nerve through the posterior approach could be an alternative method for reconstruction of the deltoid muscle in C5 through C7 root avulsion injuries. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 17275598 TI - Comparative biomechanic performances of locked cruciate four-strand flexor tendon repairs in an ex vivo porcine model. AB - PURPOSE: To investigate the effects of 3 different locking configurations on repair strength when used in a cruciate four-strand repair. METHODS: Sixty fresh porcine flexor tendons were transected and repaired with cruciate four-strand core suture repairs with 3 different locking configurations: simple locks (a modification of the Pennigton method), circle locks, and cross locks. Half of the repairs in each locking group were reinforced with a peripheral suture. The tendon repairs were subjected to linear load-to-failure testing. Outcome measures were 2-mm gap force and ultimate tensile strength. RESULTS: The cross lock repair had significantly greater 2-mm gap force and ultimate tensile strength than the simple lock repair, both with and without a peripheral suture. The cross lock repair showed significantly greater 2-mm gap force without a peripheral suture and significantly greater ultimate tensile strength with a peripheral suture than the circle lock repair. With peripheral reinforcement, the cross lock cruciate repair had a mean 2-mm gap force of 92 N and ultimate tensile strength of 119 N. The cross lock cruciate repair consistently produced the strongest biomechanic performance in all outcome measures. CONCLUSIONS: Locking configuration influences the biomechanic performance of cruciate four-strand flexor tendon repairs. Our results suggest that the cruciate repair with cross locks is stronger than repairs with simple locks or circle locks. Whether the results of this ex vivo porcine linear model can be translated to the clinical arena is unknown, because the factors of tendon/sheath friction, tendon healing, and compromised tendon viability from the lock were not addressed. PMID- 17275599 TI - Multiple extensor tendon ruptures with advanced Kienbock's disease. AB - We describe a patient with spontaneous multiple extensor tendon ruptures that were caused by a displaced fragment of the lunate in advanced Kienbock's disease. Complete excision of the lunate, limited carpal fusion, and extensor tendon reconstructions relieved the patient's symptom and restored function. PMID- 17275600 TI - Posterolateral rotatory instability of the elbow with insufficient coronoid process of the ulna: a report of 3 patients. AB - Congruity of the ulnohumeral joint, especially its anterior portion, is an important stabilizer of the elbow joint. We report on 3 patients in whom the insufficiency of the coronoid process, such as nonunion or a flattened trochlear notch, was associated with posterolateral rotatory instability of the elbow. In our opinion, addressing the anterior bony integrity of the ulnohumeral joint, in addition to the ligamentous stabilizer and mechanical axis, is essential to achieve stability in these circumstances. This issue is discussed with a review of the literature. PMID- 17275601 TI - Predicting the outcome of surgery for the proximal interphalangeal joint in Dupuytren's disease. AB - PURPOSE: We prospectively studied the outcome of limited Dupuytren's fasciectomy, in combination with joint release if necessary, for disease involving 49 proximal interphalangeal joints (PIPJs) to identify factors that predispose to recurrent PIPJ contracture. METHODS: Thirty-seven patients were treated over a 4-year period. The flexion contracture of the PIPJ was measured before surgery, immediately after surgery, and at more than 1 year after surgery. RESULTS: A mean preoperative flexion contracture of 67 degrees +/- 22 degrees was corrected to 6 degrees +/- 10 degrees at the time of surgery and 25 degrees +/- 25 degrees at the follow-up evaluation. There was a positive correlation between the severity of the preoperative flexion contracture and recurrent deformity, with a preoperative contracture greater than 60 degrees leading to significantly worse outcome. Incomplete correction of PIPJ flexion contracture during surgery and poor postoperative compliance with therapy were also associated with worse recurrent joint contractures. The digit involved and the necessity for joint release did not significantly affect outcome. CONCLUSIONS: In the absence of recurrent Dupuytren's disease, severe preoperative deformity, incomplete correction at surgery, and noncompliance with therapy predispose patients to worse PIPJ contracture. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II. PMID- 17275602 TI - Cutaneous perforators of the fourth dorsal interosseous space: anatomic study. AB - PURPOSE: Many investigators have studied the vascular anatomy of the dorsal metacarpal arteries but little attention has been paid to the exact distribution of the cutaneous perforators of the dorsum of the hand. We present an anatomic study of the cutaneous perforators within the fourth dorsal interosseous space, which was supposed to have the most inconsistent vascular anatomy. METHODS: Twenty hands were dissected after black latex injection. A skin paddle was outlined along the fourth dorsal metacarpal space. Suprafascial dissection was performed, preserving any vessel piercing the fascia and reaching the skin. Each perforator was traced back to its origin. The location and origin of each perforator was recorded by digital pictures and measured from a reference point. RESULTS: In 17 of the cases (85%) at least 1 perforator was identified within the fourth space piercing the dorsal interosseous muscle fascia and reaching the skin. In 10 hands, a perforator branching off the proximal communicating branch was identified, located a mean distance of 11 mm from the carpometacarpal joint line. CONCLUSIONS: A dissectable perforator was found consistently (17 of 20; 85%) in the proximal third of the fourth dorsal interosseous space branching off the proximal communicating branch. Few perforators branch off the middle third of the dorsal metacarpal artery. The perforator described herein shows the connection between the superficial and deep vascular systems of the ring and small metacarpal spaces, and establishes the anatomic basis for reconstructive flaps. PMID- 17275603 TI - Extensive cutaneous metastatic breast carcinoma of the hand and upper extremity: a case report. AB - Cutaneous metastatic breast carcinoma involving the hand is extremely rare. We report a case of a 39-year-old woman with a history of recurrent invasive ductal adenocarcinoma of the breast who had a right modified radical mastectomy, chemotherapy, and radiation therapy before presenting to our institution with extensive cutaneous metastasis to the upper limb including the hand. The presentation, pathogenesis, incidence, prognosis, management, and differential diagnosis of cutaneous metastatic breast carcinoma to the hand and upper limb are discussed. PMID- 17275604 TI - Bone-tissue-bone repairs for scapholunate dissociation. AB - Scapholunate dissociation is a commonly seen and treated form of carpal instability. Several surgical options have been used for the repair of scapholunate instability over the past 50 years. These have included benign neglect, reduction and percutaneous pinning, primary repair, partial fusions, tendon weaves, and combinations of these. Recent advancements in scapholunate repair and anatomy have been aimed at a more physiologic repair. Composite replacement of the entire scapholunate interval, similar to other tendon repairs seen in orthopedic surgery, has become popular. Bone-tissue-bone (BTB) autograft replacement from the foot has been used but the problems of a secondary surgical site have resulted in other graft site selections. Currently more commonly used grafts are bone-retinaculum-bone, third or second metacarpal-carpal bone, or hamate-capitate grafts, all performed with or without screw augmentation. Vascularized autograft replacement on pedicled grafts from the hand is being explored. This review discusses the surgeons' indications and technical details of the surgery. The lack of long-term outcome measurements for these BTB surgeries makes it difficult for the hand surgeon to determine the appropriate use of these treatment modalities, but early reports have indicated that the BTB graft will be an important part of scapholunate dissociation treatment. PMID- 17275605 TI - Multiple-loop, uniform-tension flexor pulley reconstruction. AB - A technique of pulley reconstruction using multiple loops of gracilis allograft tendon with uniform tension through all the loops is described. PMID- 17275606 TI - A simple, semirigid, and surgeon-friendly tendon retriever and flexor sheath dilator. AB - The repair of flexor tendons remains a challenge to the hand surgeon, and zone II repair requires a trained and experienced surgeon for good results. If the tendon has retracted proximally, however, its retrieval through the inflamed and swollen flexor sheath in acute cases and through a shrunken flexor sheath in case of a delayed repair/reconstruction can test any surgeon's skill and patience. Although there are many methods described in the literature for tendon retrieval, most are either not successful or are traumatic to the tendon or its fibrous sheath. We herein describe a semirigid tendon retriever that can be made intraoperatively and is useful in both acute and delayed repairs/reconstructions. The extremely low cost is a special feature. It has been proven to be a simple and effective method of tendon retrieval and also a flexor sheath dilator in delayed repairs/reconstructions. PMID- 17275607 TI - Solitary osteochondroma of the metacarpal. PMID- 17275608 TI - Diffusion tensor encoding schemes optimized for white matter fibers with selected orientations. AB - A method to produce gradient encoding schemes that minimize the noise of diffusion tensor imaging (DTI) indices for selected fiber orientations has been developed. The accuracy of DTI measurements depends on the gradient encoding scheme used. Most current acquisition schemes contain diffusion directions uniformly distributed in 3D space in order to provide equal noise levels for fibers in any orientation. However, when considering specific fiber bundles such as the corticospinal tract (CST) or parts of fiber bundles, the range of fiber orientations of interest may be limited. We hypothesized that, when studying fiber tracts with a limited range of orientations, measuring diffusion in directions that are uniformly distributed in 3D space may be suboptimal for the noise levels of various DTI indices. Therefore, we first used simulations to determine six diffusion directions that minimize the noise of DTI measurements for selected fiber orientations. The resulting optimized set of directions was then tested on the right CST of a healthy human subject, and its performance was compared with that of conventional acquisition strategies. Both the simulations and the experiments on the human subject demonstrated that the new scheme significantly reduced the standard deviation of DTI indices for tensors with primary eigenvectors within a selected range of orientations. PMID- 17275609 TI - Exploratory voxel-based analysis of diffusion indices and hemispheric asymmetry in normal aging. AB - Age-related microstructural changes in brain white matter can be studied by utilizing indices derived from diffusion tensor imaging (DTI): apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The objective of this study is to examine alterations in FA and ADC by employing exploratory voxel-based analysis (VBA) and region(s) of interest (ROI)-based analysis. A highly nonlinear registration algorithm was used to align the ADC and FA image volumes of different subjects to perform accurate voxel-level statistics for two age groups, as well as for hemispheric asymmetry for both age groups. VBA shows significant age-related decline in FA with frontal predominance (frontal white matter, and genu and anterior body of the corpus callosum), superior portions of a splenium and highly oriented fibers of the posterior limb of the internal capsule and the anterior and posterior limbs of the external capsule. Hemispheric asymmetry of FA, as assessed by VBA, showed that for the young-age group, significant right greater-than-left asymmetry exists in the genu, splenium and body of the corpus callosum and that left-greater-than-right asymmetry exists in the anterior limb of the external capsule and in the posterior limb of the internal capsule, thalamus, cerebral peduncle and temporal-parietal regions. VBA of the hemispheric asymmetry of the middle-age group revealed much less asymmetry. Regions showing age-related changes and hemispheric asymmetry from VBA were, for a majority of the findings, in conformance with ROI analysis and with the known pattern of development and age-related degradation of fiber tracks. The study shows the feasibility of the VBA of DTI indices for exploratory investigations of subtle differences in population cohorts, especially when findings are not localized and/or known a priori. PMID- 17275611 TI - Improved cerebrospinal fluid flow measurements using phase contrast balanced steady-state free precession. AB - We present a demonstration of phase contrast balanced steady-state free precession (PC-bSSFP) for measuring cerebrospinal fluid (CSF) flow in the brain and spine, and a comparison of measurements obtained with this technique to conventional phase contrast using incoherent gradient echoes (PC-GRE). With PC GRE sequences, CSF images suffer from low signal-to-noise ratio (SNR), due to short repetition times required for adequate temporal resolution, and the long relaxation time of CSF. Furthermore, CSF flow is often nonlaminar, causing phase dispersion and signal loss in PC-GRE images. It is hypothesized that PC-bSSFP can improve CSF flow measurements with its high SNR and insensitivity to turbulent flow effects. CSF images acquired from the two techniques were compared in 13 healthy volunteers. Three measures were used to objectively evaluate the PC-bSSFP sequence: the CSF flow percentage, defined as the percentage of the total CSF region exhibiting pulsatile flow, net stroke volume and SNR. Images acquired with PC-bSSFP demonstrated pulsatile CSF flow in 35.8% (P<.005), 11.2% (P<.05) and 27.8% (P<.0005) more pixels than PC-GRE in the prepontine cistern, anterior and posterior cervical subarachnoid space (SAS), respectively. Likewise, measurements of stroke volume in these regions increased by 61.6% (P<.05), 16.8% (P<.001) and 48.3% (P<.0001), respectively. Similar comparisons in the aqueduct showed no statistical difference in stroke volumes between the two techniques (P=.5). The average gain in SNR was 3.3+/-1.7 (P<.001) in the prepontine cistern, 5.0+/-0.2 (P<.01) at the cervical level and 2.0+/-0.4 (P<.001) in the aqueduct in PC-bSSFP magnitude images over PC-GRE images. In addition to the obvious advantage of increased SNR, these results indicate that PC-bSSFP provides more complete measurements of CSF flow data than PC-GRE. PC-bSSFP can be used as a reliable technique for CSF flow quantification for the characterization of normal and altered intracranial CSF flow patterns. PMID- 17275610 TI - Diffusion tensor imaging of native and degenerated human articular cartilage. AB - Diffusion tensor imaging (DTI) is potentially sensitive to collagen degeneration in cartilage. In this study, DTI was measured on human cartilage samples with interventions of trypsin and collagenase. The measured preferred diffusion direction was consistent with the zonal structure of collagen network. The glycosaminoglycan concentration decreased and apparent diffusion coefficient increased with both interventions. The fractional anisotropy (FA) was not affected by trypsin and showed a slight increase with combined trypsin and collagenase intervention. DTI in cartilage is technically challenging due to the low FA and the almost undetectable change with collagen disruption seen here. PMID- 17275613 TI - Flexible statistical modelling detects clinical functional magnetic resonance imaging activation in partially compliant subjects. AB - Clinical functional magnetic resonance imaging (fMRI) occasionally fails to detect significant activation, often due to variability in task performance. The present study seeks to test whether a more flexible statistical analysis can better detect activation, by accounting for variance associated with variable compliance to the task over time. Experimental results and simulated data both confirm that even at 80% compliance to the task, such a flexible model outperforms standard statistical analysis when assessed using the extent of activation (experimental data), goodness of fit (experimental data), and area under the operator characteristic curve (simulated data). Furthermore, retrospective examination of 14 clinical fMRI examinations reveals that in patients where the standard statistical approach yields activation, there is a measurable gain in model performance in adopting the flexible statistical model, with little or no penalty in lost sensitivity. This indicates that a flexible model should be considered, particularly for clinical patients who may have difficulty complying fully with the study task. PMID- 17275612 TI - Derivative temporal clustering analysis: detecting prolonged neuronal activity. AB - Temporal clustering analysis (TCA) and independent component analysis (ICA) are promising data-driven techniques in functional magnetic resonance imaging (fMRI) experiments to obtain brain activation maps in conditions with unknown temporal information regarding the neuronal activity. Although comparable to ICA in detecting transient neuronal activities, TCA fails to detect prolonged plateau brain activations. To eliminate this pitfall, a novel derivative TCA (DTCA) method was introduced and its algorithms with different subtraction intervals were tested on simulated data with a pattern of prolonged plateau brain activation. It was found that the best performance of DTCA method in generating functional maps could be obtained if the subtraction interval is equal to or larger than the length of the rising time of the fMRI response. The DTCA method and its theoretical predication were further investigated and validated using in vivo fMRI data sets. By removing the limitations in the previous TCA, DTCA has shown its powerful capability in detecting prolonged plateau neuronal activities. PMID- 17275615 TI - MRI description of knee medial collateral ligament abnormalities in the absence of trauma: edema related to osteoarthritis and medial meniscal tears. AB - A retrospective case series regarding the knees of 12 adult patients with MRI abnormalities of the medial collateral ligament (MCL), but without clinical history of trauma to the MCL, were collected and compared with six knee MR images from patients with clinical traumatic injuries to their MCLs. The MR images were studied for the extent of edema of the MCL, as well as other associated findings. Edema of the MCL on MRI could be found in three distinct categories of patients: (a) those with trauma to the MCL, which was an expected finding; (b) those without trauma but with medial compartment osteoarthritis; and (c) those without trauma but with degenerative medial meniscal tears. The clinical significance, if any, of the edema found in MCLs without trauma remains unclear. Atraumatic MCL edema may serve as a marker for medial knee compartment osteoarthritis or for a degenerative medial meniscal tear and should not be confused with traumatically induced MCL injuries, although this distinction can often be difficult to make based on MRI findings alone. PMID- 17275614 TI - Automatic 3D tracking of cardiac material markers using slice-following and harmonic-phase MRI. AB - A method to track a grid of cardiac material points in three dimensions using slice-following (SF) tagged magnetic resonance imaging (MRI) and harmonic-phase MRI is presented. A three-dimensional grid of material points on the lines of intersections of short-axis (SA) and long-axis (LA) planes is automatically tracked by combining two-dimensional pathlines that are computed on both SA and LA image planes. This process yields the true three-dimensional motion of points originating on the image plane intersections. Experimental data from normal volunteers, each obtained in four short breath-holds using the SF harmonic phase MRI pulse sequence, is presented. A validation of two-dimensional in-plane tracks using this pulse sequence on a moving phantom is also presented. PMID- 17275616 TI - Investigations of silicone breast implants with the NMR-MOUSE. AB - Silicone breast implants are used for breast augmentation and breast reconstruction. The issues of concern associated with such implants are: (a) the quality control of each implant before implantation, and (b) the detection of implant bleeding after implantation. We have studied the use of the Nuclear Magnetic Resonance-MObile Universal Surface Explorer (NMR-MOUSE) for the nondestructive testing of (a) the quality of implant shells, and (b) changes in implant gel due to leakage of body fluid into the implant. Depth profiles measured nondestructively through implant shells at different positions of each implant by the Profile NMR-MOUSE assured good reproducibility of the quality and thickness of different shell layers. The leakage of implants upon rupture was mimicked by observing changes in the transverse NMR relaxation time of the implant gel upon ingress of physiological saline solution and safflower oil through the rupture. Results demonstrate that nondestructive testing with unilateral NMR is a potential method for use in the quality control of implants and for the screening of implants for rupture after implantation. PMID- 17275617 TI - In vivo measurement of tissue damage, oxygen saturation changes and blood flow changes after experimental traumatic brain injury in rats using susceptibility weighted imaging. AB - Traumatic brain injury (TBI) is a prevalent disease, and many TBI patients experience disturbed cerebral blood flow (CBF) after injury. Moreover, TBI is difficult to quantify with conventional imaging modalities. In this paper, we utilized susceptibility weighted imaging (SWI) as a means to monitor functional blood oxygenation changes and to quantify CBF changes in animals after trauma. In this study using six rats, brain trauma was induced by a weight drop model and the brain was scanned over four time points: pre trauma, and 4 h, 24 h and 48 h post trauma. Five rats survived and one died after trauma. A blood phase analysis using filtered SWI phase images suggested that three rats recovered after 48 h and two rats deteriorated. SWI also suggested that CBF decreased by up to 26%. The CBF change is in agreement with the results of arterial spin labeling methods conducted in this study and with previously published results. Furthermore, SWI revealed an enlargement of the major venous vasculature in deep brain structures, in accordance with the location of diffuse axonal injury. Compared with the traditional, invasive, clinical monitoring of cerebral vascular damage and reduction in blood flow, this method offers a novel, safe and noninvasive approach to quantify changes in oxygen saturation and CBF and to visualize structural changes in blood vasculature after TBI. PMID- 17275618 TI - Correlation between serum ferritin levels and liver iron concentration determined by MR imaging: impact of hematologic disease and inflammation. AB - Liver iron concentration was determined in 28 patients by magnetic resonance imaging using the method of Gandon et al. (Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004;363:357-362). The result showed a significant correlation with blood plasma ferritin content (Spearman's r=.66; P<.001) and a slightly improving correlation coefficient when limited to those patients not known to have inflammation (r=.82; n=17; P<.001). Zooming in on patients with hematologic disease also had a beneficial effect on the correlation between liver iron content and plasma ferritin level (r=.79; n=13; P=.001). It is concluded that in patients without inflammation and in patients with hematologic disease, the content of ferritin in blood is a better predictor of liver iron content than in other patient categories. PMID- 17275619 TI - Comparison of delayed myocardial enhancement in the early and late phase after contrast injection: is it possible to reduce the examination time for myocardial viability study? AB - OBJECTIVES: We studied whether we can obtain a myocardial viability study immediately after contrast injection to reduce the whole cardiac MR examination time. MATERIALS AND METHODS: We examined 36 patients with cardiovascular abnormality on comprehensive cardiac MRI. T1-weighted images with inversion recovery (IR) were obtained 5 min after stress perfusion with 0.05 mmol/kg of gadodiamide and 15 min after the resting perfusion with the same dose. (The latter images were obtained 25 min after the initial administration.) We evaluated the existence, the number of sectors, and the degree of enhancement at each time. The contrast ratio was also calculated. The number of the enhanced sectors and the contrast ratio were statistically compared using Student's t test. RESULTS: All 17 cases of delayed myocardial enhancement at 25 min after contrast injection showed some enhancement at 5 min after contrast injection. However, the number of enhanced sectors was larger at 25 min after the initial injection in 11 cases, and it was statistically significant (P=.017). The degree of enhancement was stronger at 25 min in 14 cases. However, the contrast ratio at 5 and 25 min after contrast injection was not significantly different (P=.245). CONCLUSION: Myocardial viability study immediately after contrast injection is too early to evaluate the extent of myocardial injury. PMID- 17275621 TI - In vivo (31)P MRS study of skeletal muscle metabolism in patients with postpolio residual paralysis. AB - The muscle metabolism of at-rest patients with varying degrees of postpolio residual paralysis (PPRP) was studied and compared with that of controls using in vivo phosphorus magnetic resonance spectroscopy. The phosphocreatine (PCr)/inorganic phosphate (Pi) and PCr/adenosine triphosphate ratios were lower in patients than in controls. Reduction in PCr/Pi suggests abnormalities in oxidative phosphorylation. A significant increase was observed in the phosphomonoester/PCr ratio in patients, indicating the accumulation of intermediary compounds of the glycolytic pathway. Furthermore, the phosphodiester/PCr ratio was also significantly increased in patients. In general, the observed changes in metabolite ratios were found to be related to the degree of residual paralysis, suggesting that metabolic changes are secondary to chronic neurogenic processes. These metabolic alterations appear to be the possible cause of energy deficit and underlying muscle fatigue in PPRP patients. The present results provide an insight into the metabolic impairment and degree of muscle damage in patients with PPRP. PMID- 17275620 TI - Perfusion MR imaging and proton MR spectroscopic imaging in differentiating necrotizing cerebritis from glioblastoma multiforme. AB - We describe a lesion with the magnetic resonance imaging (MRI) characteristics of a glioblastoma mutiforme and demonstrate how perfusion MRI and proton MR spectroscopic imaging can be used to differentiate necrotizing cerebritis from what appeared to be a high-grade glioma. A 43-year-old woman presented to her physician complaining of progressive visual disturbance and headache for several weeks. Conventional MRI demonstrated a parietal peripherally enhancing mass with central necrosis and moderate to severe surrounding T2 hyperintensity, suggesting an infiltrating high-grade glioma. However, advanced imaging, including dynamic susceptibility contrast MRI (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI), suggested a nonneoplastic lesion. The DSC MRI data demonstrated no hyperperfusion within the lesion and surrounding T2 signal abnormality, and the MRSI data showed overall decrease in metabolites in this region, except for lactate. Because of the aggressive appearance to the lesion and the patients' worsening symptoms, a biopsy was performed. The pathologic diagnosis was necrotizing cerebritis. After the commencement of steroid therapy, imaging findings and patient symptoms improved. This report will review the utility of advanced imaging for differentiating inflammatory from neoplastic appearing lesions on conventional imaging. PMID- 17275622 TI - Spectral resolution enhancement by chemical shift imaging. AB - Three-dimensional chemical shift imaging (3D CSI) with appropriate data postprocessing can be used as a tool to improve spectral resolution in samples where large susceptibility differences and limited shim capabilities prevent good sample shimming. Data postprocessing is reduced to the realignment of individual 3D voxel spectra. As a result, the line broadening due to the field inhomogeneity over the sample's volume is reduced to the broadening by inhomogeneity within individual voxels. We compared this method with the resolution enhancement by window multiplication. We demonstrated, theoretically and experimentally, that in the presence of large, lower-order gradients, 3D CSI achieves better resolution enhancement with smaller sensitivity losses. An application of the method to a simple biological system is presented as well. PMID- 17275624 TI - Magnetic resonance imaging segmentation techniques using batch-type learning vector quantization algorithms. AB - In this article, we propose batch-type learning vector quantization (LVQ) segmentation techniques for the magnetic resonance (MR) images. Magnetic resonance imaging (MRI) segmentation is an important technique to differentiate abnormal and normal tissues in MR image data. The proposed LVQ segmentation techniques are compared with the generalized Kohonen's competitive learning (GKCL) methods, which were proposed by Lin et al. [Magn Reson Imaging 21 (2003) 863-870]. Three MRI data sets of real cases are used in this article. The first case is from a 2-year-old girl who was diagnosed with retinoblastoma in her left eye. The second case is from a 55-year-old woman who developed complete left side oculomotor palsy immediately after a motor vehicle accident. The third case is from an 84-year-old man who was diagnosed with Alzheimer disease (AD). Our comparisons are based on sensitivity of algorithm parameters, the quality of MRI segmentation with the contrast-to-noise ratio and the accuracy of the region of interest tissue. Overall, the segmentation results from batch-type LVQ algorithms present good accuracy and quality of the segmentation images, and also flexibility of algorithm parameters in all the comparison consequences. The results support that the proposed batch-type LVQ algorithms are better than the previous GKCL algorithms. Specifically, the proposed fuzzy-soft LVQ algorithm works well in segmenting AD MRI data set to accurately measure the hippocampus volume in AD MR images. PMID- 17275623 TI - A novel, fast entropy-minimization algorithm for bias field correction in MR images. AB - A novel, fast entropy-minimization algorithm for bias field correction in magnetic resonance (MR) images is suggested to correct the intensity inhomogeneity degradation of MR images that has become an increasing problem with the use of phased-array coils. Four important modifications were made to the conventional algorithm: (a) implementation of a modified two-step sampling strategy for stacked 2D image data sets, which included reducing the size of the measured image on each slice with a simple averaging method without changing the number of slices and then using a binary mask generated by a histogram threshold method to define the sampled voxels in the reduced image; (b) improvement of the efficiency of the correction function by using a Legendre polynomial as an orthogonal base function polynomial; (c) use of a nonparametric Parzen window estimator with a Gaussian kernel to calculate the probability density function and Shannon entropy directly from the image data; and (d) performing entropy minimization with a conjugate gradient method. Results showed that this algorithm could correct different types of MR images from different types of coils acquired at different field strengths very efficiently and with decreased computational load. PMID- 17275625 TI - Sequential anisotropic Wiener filtering applied to 3D MRI data. AB - We present three different sequential Wiener filters, namely, isotropic, orientation and anisotropic. The first one is similar to the classical Wiener filter in the sense that it uses an isotropic neighborhood to estimate its parameters. Here we present a sequential version of it. The orientation Wiener filter uses oriented neighborhoods to estimate the structure orientation present at each voxel, giving rise to a modified estimator of the parameters. Finally, the anisotropic Wiener filter combines both approaches adaptively so that the appropriate approach is locally selected. Several synthetic experiments are presented showing the performance of the filters with respect to their parameters. A mean square error analysis is performed using a publicly available magnetic resonance imaging (MRI) brain phantom and a comparison with other filtering approaches is carried out. In addition, results from filtering real MRI data are presented. PMID- 17275627 TI - Kneeling kinematics after total knee arthroplasty: anterior-posterior contact position of a standard and a high-flex tibial insert design. AB - Deep flexion activities including kneeling are desired by patients after total knee arthroplasty. This in vivo radiographic study sought to reveal the effect of tibial insert design on tibiofemoral kinematics during kneeling. One group of patients received standard posterior stabilized tibial inserts, whereas the other group received posterior stabilized tibial inserts (Flex inserts) that were designed to allow more flexion. The patients with the Flex inserts achieved greater range of motion without different tibiofemoral contact behavior. PMID- 17275626 TI - Comparison of conventional versus computer-navigated acetabular component insertion. AB - This retrospective study compared the efficacy of computer navigation and conventional freehand techniques to place acetabular component orientation in the target position of acetabular cup inclination of 45 degrees and anteversion of 20 degrees . We selected 69 patients who had undergone total hip arthroplasty with freehand cup insertion who had computed tomography (CT) to plan for acetabular cup placement of the contralateral side. This group was compared with 98 patients who underwent CT-based cup insertion, and all had postoperative CT. After CT based cup placement, average cup position was 43 degrees inclination (95% confidence interval [CI], 0.97; range, 30 degrees -58 degrees ) and 22.2 degrees anteversion (95% CI, 1.72; range, 5 degrees -38 degrees ). For freehand, average cup position was 45.7 degrees inclination (95% CI, 2.63 degrees ; range, 26 degrees -64 degrees ) and 28.5 degrees anteversion (95% CI, 3.80 degrees ; range, 9 degrees -53 degrees ). F ratio was 5.56 for inclination and 3.67 for anteversion (P < .0001). This study demonstrated substantial statistical improvement in accuracy of cup placement using CT-based navigation compared with freehand methods. PMID- 17275628 TI - Iliopsoas tendonitis a complication after total hip arthroplasty. AB - The causes of pain after total hip arthroplasty are multiple. We present a series of 15 patients (16 cases) who presented with pain related to the iliopsoas tendon. All patients had previously undergone cementless hip arthroplasty and presented with similar symptoms and clinical signs. Surgery was carried out after failure of conservative measures. Release of the iliopsoas tendon from the lesser trochanter gave good symptomatic relief in all except one patient who required reposition of acetabular prosthesis, with the average Harris Hip Score improving from 58 (range, 44-70) to 91 (range, 78-95) postoperatively. This relatively uncommon condition should be considered in the differential diagnosis of all patients who present with groin pain after total hip arthroplasty. Surgical release of the iliopsoas tendon can give excellent results in these patients. PMID- 17275629 TI - Return to athletic activity after total hip arthroplasty. Consensus guidelines based on a survey of the Hip Society and American Association of Hip and Knee Surgeons. AB - A web-based survey was developed to evaluate joint arthroplasty surgeon's preferences for the return to sporting activities after total hip arthroplasty. This survey listed 30 groups of activities (37 specific sports) and was sent to all members of the Hip Society and American Association of Hip and Knee Surgeons. All surgeons were asked to grade each activity as follows: allow, allow with experience, not allowed, or undecided. Results were computed using a power analysis, Z test, and chi(2) test to determine statistical significance. There were a total of 549 responses giving an overall response rate of 72%, with 93% (92/99) of the Hip Society members and 72% (522/727) of American Association of Hip and Knee Surgeons members responding to the survey. Consensus guidelines and postoperative timing for the return to specific activities are presented. PMID- 17275630 TI - Five-year results of metal-on-metal resurfacing arthroplasty in Asian patients. AB - Clinical results of 50 metal-on-metal resurfacing arthroplasties in 45 Japanese patients were evaluated to a minimum follow-up of 5 years. The predominant diagnosis was developmental dysplasia or dislocation of the hip (70%). One patient died of an unrelated cause and another was lost to follow-up. Two hips received revision surgery, including 1 femoral neck fracture and 1 septic loosening. In the remaining 46 hips, 1 hip showed femoral component loosening. Clinical scores of the 46 hips were satisfactory at the final follow-up. The survival rate at 5 years was 96% when failure was attributed to revision for any reason. Metal-on-metal resurfacing arthroplasty in Japanese patients, who have a different distribution of hip diseases from European and American patients, showed similarly promising early clinical results. PMID- 17275631 TI - Cementless alumina-on-alumina total hip arthroplasty in patients younger than 50 years: a 5-year minimum follow-up study. AB - Sixty-seven patients (78 hips) who were younger than 50 years underwent cementless total hip arthroplasty using a porous-coated acetabular cup, an alumina liner, a 28-mm alumina head, and a proximally porous-coated femoral stem. One patient (1 hip) died and 2 patients (3 hips) were lost to follow-up. The remaining 64 patients (74 hips) were followed for 5 to 6 years. Their mean age at the index operation was 37 years. The mean Harris hip score was 94 points at the time of final follow-up. Four patients (4 hips) had mild thigh pain. All acetabular and femoral components were bone-ingrown, and neither pelvic nor femoral osteolysis was identified. No fracture of the ceramic liner or head was identified. Wear of the ceramic components was undetectable in 27 hips in which measurement was possible. PMID- 17275632 TI - The position of the bipolar cup reflects the direction of the hip contact force acting on it. AB - We radiographically measured the bipolar cup position to analyze the direction of joint force acting on the bipolar cup. The abduction angle of the bipolar cup was measured in each radiograph taken immediately and at six 12 weeks and yearly after the operation. Radiographs in patients with weight bearing were also investigated. The results indicated that the abduction angle of the bipolar cup was 24.1 degrees +/- 11.2 degrees immediate postoperatively and was 16.2 degrees +/- 5.1 degrees at 6 weeks, 16.1 degrees +/- 5.1 degrees at 3 months, and 16.2 degrees +/- 5.1 degrees at 1 year. The cup abduction angles with weight bearing were not different from those without weight bearing and were 15.9 degrees +/- 4.9 degrees , 16.2 degrees +/- 4.4 degrees , and 16.1 degrees +/- 4.7 degrees on the supine, double-legged stance, and single-legged stance radiographs, respectively. Because the position of the bipolar cup reflects the direction of loads pivoting on it, the direction of the joint force in the frontal plane acting on the bipolar prosthesis is about 16 degrees to vertical. PMID- 17275633 TI - The mid-term results of a dual offset uncemented stem for total hip arthroplasty. AB - The Synergy stem is a third-generation proximal in-growth, tapered titanium alloy uncemented stem, with standard and high offset versions. Two hundred ten primary hip arthroplasties were performed using the Synergy stem in 193 patients. There were 124 males and 69 females with an average age of 58 years (range, 22-85 years). The average follow-up was 75 months (range, 60-96 years). Only 1 stem has required revision, for a stem survival rate of 99.5%. The overall incidence of thigh pain was 2.8%. Intraoperative undisplaced fractures of the proximal femur occurred in 3.3% of patients and were managed at the time with wiring, with no effect on outcome. Minor osteolysis was seen proximally in 10% of patients, but no osteolysis was seen distal to the porous coating. PMID- 17275634 TI - A second-generation cementless total hip arthroplasty mean 9-year results. AB - Two hundred fifty-eight primary total hip arthroplasties in 231 patients were implanted using a circumferentially, proximally porous-coated, collared femoral component and a cementless, hemispherical, porous-coated acetabular component and followed up for a mean of 9 years (5-14 years). Four femoral components were revised (2 stems for infection and 2 stems for aseptic loosening). One additional femoral component was radiographically loose at last follow-up. Nine hips underwent acetabular revision (4 for instability, 2 for infection, 2 for loosening, and 1 for osteolysis). Ten-year survivorship with revision or loosening of any component as the end point was 92%; with femoral component aseptic loosening as end point, survivorship was 98%; with acetabular aseptic loosening as the end point, survivorship was 99%. Osteolysis was identified in 26 hips (13%). PMID- 17275635 TI - Surgeon energy expenditure during total joint arthroplasty. AB - Although there is extensive literature related to total hip arthroplasty (THA) and total knee arthroplasty (TKA), most of this research has been devoted to analyzing patient outcomes and complications. There are no published articles to date investigating the energy expenditure of the surgeon during these procedures. Using a SenseWear Pro(2) Armband, energy expenditure measured as energy expended during 22 primary THAs or TKAs by a single surgeon was recorded. Total hip arthroplasty required a greater expenditure of energy than TKA (P < .05). No significant trend was detected when comparing patient body mass index to the number of calories used by the surgeon. The physiologic demands placed upon the surgeon for various procedures should be recognized and is an additional factor to consider when determining procedure reimbursement. PMID- 17275636 TI - The effectiveness of warfarin dosing from a nomogram compared with house staff dosing. AB - The purpose of this study is to address the safety and efficacy of a warfarin dosing nomogram. Patients undergoing hip or knee arthroplasty were randomized to warfarin dosed by nomogram (n = 106) or by house staff (n = 110) during their hospital stay. The average daily dose of warfarin was 4.14 mg for the nomogram group and 4.18 mg for the house staff group. On postoperative day 4, the average international normalized ratio was 1.55 in the nomogram group compared with 1.59 in the house staff group. On postoperative day 4, 19.1% of the patients in the nomogram group had a therapeutic international normalized ratio, compared with 14.7% in the house staff group. There were no differences in bleeding or thrombotic complications in the 2 groups. This nomogram appears to be both safe and effective. PMID- 17275638 TI - Functional outcomes after nonrecurrent dislocation of primary total hip arthroplasty. AB - The influence of dislocation on functional outcomes of primary total hip arthroplasty is unclear. The purpose of this study was to assess the effect of nonrecurrent dislocations treated with closed reduction after primary total hip arthroplasty on postoperative outcome in the short to medium term. Ninety-six patients were enrolled in this retrospective case-control study. There were 32 patients who had a postoperative dislocation. The control group consisted of 64 matched patients who did not dislocate. All patients had a minimum of 1-year follow-up. The 2 groups were compared using the SF-12, reduced WOMAC, and satisfaction questionnaire. There was no statistical difference between the 2 groups in subjective functional outcomes using the WOMAC or SF-12. However, there was a trend toward better quality of life scores in the control group, and they were more satisfied with their surgery compared with the dislocation group. PMID- 17275637 TI - Use of palpable tendons for extramedullary tibial alignment in total knee arthroplasty. AB - For extramedullary tibial alignment in total knee arthroplasty, it is important to localize the center of the ankle mortise. Malpositioning of alignment jigs can produce varus or valgus implantation and can lead to inferior clinical and radiologic outcomes. In a cadaver study, we investigated the accuracy of palpable tendons as references for extramedullary tibial alignment in 86 anatomical specimens. To investigate tendon movement with pronation and supination in living patients, we additionally performed 10 magnetic resonance imaging scans. On average, the lateral border of the tibialis anterior tendon was measured 1 cm medial to the center of the talus. The extensor hallucis longus tendon was the most accurate anatomical landmark. Pronation had a small effect, but extensive supination can lead to tendon deviation greater than 1 cm. Our results suggest that the extensor hallucis longus can serve as a useful intraoperative reference to identify the center of the ankle mortise, particularly if marked preoperatively. PMID- 17275639 TI - Unstable hemiarthroplasty of the hip-treated with a simple technique of acetabular augmentation. AB - Hemiarthroplasty of the hip is one of the most frequently performed orthopedic procedures for trauma in the elderly. Dislocation is one of its well-recognized complications and ranges from 1% to 16% (Acta Orthop Scand. 2003;74:45-48) in different series. Often, dislocation can be recurrent when the morbidity is even higher. Suggested methods of treatment for this difficult problem range from closed/open reduction followed by conservative management to Girdlestone excision arthroplasty. We report a unique, simple, and effective method of managing this problem, particularly in those elderly patients who are medically unfit to undergo a total hip arthroplasty or a major revision hip surgery at a later date for a dislocated hemiarthroplasty. Nine patients have been treated with our technique, and none of these patients had a further dislocation over a 6-month to 9-year follow-up. PMID- 17275640 TI - The clinical consequences of flexion gap asymmetry in total knee arthroplasty. AB - This study was carried out to compare femoral component rotation of 18 knees from 18 patients who suffered from lateral flexion instability after total knee arthroplasty (Western Ontario and McMaster University Osteoarthritis [WOMAC], 6.4 points; International Knee Society [IKS] score, 119 points) with 10 asymptomatic controls (WOMAC, 0.1 points; IKS score, 182 points) after total knee arthroplasty. The symptomatic patients showed increased lateral joint laxity as determined by fluoroscopic stress radiography. Femoral component rotation was determined by computed tomography scans. The femoral component rotation was more internally rotated in symptomatic patients (5.5 degrees ) than in controls (1.0 degrees ) (P = .04). Varus laxity in flexion was higher in symptomatic patients (11.0 degrees ) than in controls (7.0 degrees ) (P < .001). Increased lateral flexion laxity is associated with increased internal femoral component rotation and a less favorable clinical outcome. PMID- 17275642 TI - Total knee arthroplasty after failed high tibial osteotomy long-term follow-up of matched groups. AB - Forty patients with 51 knee arthroplasties after high tibial osteotomy were compared with a matched group of patients with primary knee arthroplasties. Patients were matched according to length of follow-up, age, sex, prosthetic design, and surgeon. At an average of 12.6 years, the patients were reviewed and assessed clinically using the Hospital for Special Surgery scoring system. Radiologic assessment was also performed. Although the overall Hospital for Special Surgery scores showed no significant difference between the 2 groups, there were more patients in the osteotomy group with a poor result (P = .027), significantly reduced flexion (P = .006), and higher reoperation rate. There were more failures after high tibial osteotomy. Failures tend to occur in the medium to long term, emphasizing the importance of long-term follow-up. PMID- 17275641 TI - An anatomical study of tibial metaphyseal/diaphyseal mismatch during revision total knee arthroplasty. AB - This cadaveric study determines the relationship of the tibial metaphysis and intramedullary canal of the tibia (diaphysis), particularly relating to revision knee arthroplasty. A total knee arthroplasty was performed in 20 cadaveric tibiae using revision instrumentation with a canal-filling uncemented stem. The offset, which is the distance between the center of the tibial canal and the center of the tibial metaphysis, was measured using the revision system offset bushing. The average distance between the center of the tibial metaphysis and the center of the tibial diaphysis was 4.1 mm (+/-2.9 mm) with an average angle of 105 degrees (0 degrees -70 degrees ). The mean offset was 4.1 mm (+/-2.9) and the mean offset angle was 105 degrees (0 degrees -350 degrees ). The study confirms the center of the tibial diaphysis is not congruous with the center of the metaphysis with wide variations in offsets among individuals. A wide range of offsets are necessary for optimum placement of implants. PMID- 17275643 TI - Polyethylene wear against alumina and zirconia heads in cemented total hip arthroplasty. AB - We compared the polyethylene wear of acetabular sockets articulated with 22.225 mm alumina heads with the polyethylene wear of those articulated with 22.225-mm zirconia heads in cemented total hip arthroplasty during a mean follow-up period of 5.4 years. Using a computer-aided technique, we measured polyethylene wear radiologically in 46 hips with alumina heads and 58 hips with zirconia heads. The preoperative diagnosis in all cases was osteoarthritis. The mean linear wear rate and mean volumetric wear rate of polyethylene sockets against zirconia heads were 0.133 mm/y and 39.8 mm(3)/y, respectively, significantly greater (P < .01) than the wear rates against alumina heads (0.078 mm/y and 24.2 mm(3)/y, respectively). Age at operation, patient body weight as well as height, thickness of polyethylene, and socket abduction angle did not influence the wear rates. We speculate that the excessive polyethylene wear was caused by phase transformation of zirconia, leading to an increase of surface roughness. PMID- 17275644 TI - Impingement contributes to backside wear and screw-metallic shell fretting in modular acetabular cups. AB - Eighty-six polyethylene liners and 56 metallic shells of acetabular components were evaluated by visual and stereomicroscopic examination for impingement, backside polyethylene wear, creep, and fretting at the screw-metallic shell interface using a subjective scoring system. Medical records and radiological data were available in 65 and 46 patients, respectively. Impingement was found in 62 components (75%). Backside polyethylene wear and screw-metallic shell corrosion and fretting were significantly correlated (P < .001) with impingement. Polyethylene creep was significantly correlated to backside wear and tended to be higher for the cups that had impingement (P = .06). No correlation was found between backside polyethylene wear and implant design or cup position. Our results suggest that impingement in a modular acetabular component correlated with increased backside wear and screw-metallic shell corrosion and fretting. PMID- 17275645 TI - Genetic susceptibility to total hip arthroplasty failure--positive association with mannose-binding lectin. AB - Mannose-binding lectin (MBL) may be involved in the biologic cascade of events initiated by wear debris and bacterial infection around loosened total hip arthroplasties (THAs). Individual responses to such stimuli may be dictated by genetic variation caused by single nucleotide polymorphisms (SNPs). We performed a case-control study on 4 MBL SNPs using case patients (n = 91) with aseptic loosening or deep infection (n = 71). Control subjects (n = 150) had clinically and radiologically well-fixed THAs for more than 10 years. Frequency of the C allele (P = .001) and that of the genotype C/C (P = .004) for the -550 SNP were associated with aseptic failure. The codon 54 SNP G allele (P = .012) and G/G genotype (P = .027) frequencies were associated with aseptic failure as well. In the septic group, the frequency of the C allele (P = .01) and that of the genotype C/C (P = .05) for the -550 SNP were significant. Failure of THAs may be under genetic influence to candidate susceptibility genes such as MBL. PMID- 17275646 TI - Pseudogout after total knee arthroplasty. AB - We report a case of a patient who presented with signs and symptoms of acute septic arthritis of the knee 9 years after total knee arthroplasty. Thick white purulent fluid was aspirated from the knee. Microscopy of the fluid demonstrated calcium pyrophosphate dihydrate crystals, and no organisms were cultured. The patient made a rapid recovery after the single aspiration, rest, and nonsteroidal antiinflammatory drugs alone. Eight years after this episode, the patient remains asymptomatic. To the best of our knowledge, no case of calcium pyrophosphate dihydrate arthropathy after total knee arthroplasty has been reported previously. PMID- 17275647 TI - Calcium pyrophosphate dihydrate deposition disease (pseudogout) after total knee arthroplasty. AB - The authors report a case of calcium pyrophosphate dihydrate deposition disease (pseudogout) presenting in the early period after primary total knee arthroplasty. The patient's symptoms resolved with conservative management including colchicine and indomethacin. The presentation of pseudogout resembles septic arthritis and should be included in the differential diagnosis to prevent unnecessary surgery in these patients. PMID- 17275648 TI - Intramedullary strut substitution and impaction allografting cemented revision for the treatment of a periprosthetic fracture in a severely compromised femur. AB - Revision for the treatment of a B3 periprosthetic femoral fracture often requires proximal femoral allograft arthroplasty in physiologically young or tumor prostheses in elderly patients. Extramedullary strut allograft augmentation can only be used when the host femur is structurally adequate for the insertion of the revision stem (periprosthetic femoral fractures type B2) and appears to be an attractive biological concept as early incorporation to the host bone results in a sound biomechanical construct. We report here the simultaneous use of whole femur intramedullary strut substitution along with an extramedullary strut graft placement, with impaction allografting revision to a long cemented femoral prosthesis, to augment the deficient metadiaphyseal bone stock (Paprosky type IV) for the treatment of a complex type B3 periprosthetic femoral fracture. PMID- 17275650 TI - Clostridium cadaveris septic arthritis after total hip arthroplasty in a metastatic breast cancer patient. AB - We report the first known case of septic arthritis in the setting of total hip arthroplasty caused by Clostridium cadaveris, a gas-forming anaerobic enteric organism usually considered a non-pathogen. This case occurred in a patient treated with total hip arthroplasty for metastatic breast cancer involving the acetabulum. The patient was managed successfully with debridement, prosthetic retention, and chronic antibiotic suppression. We propose this mode of care as a successful alternative for some patients with prosthetic joint infection and prohibitive comorbid conditions. PMID- 17275649 TI - Acetabular prosthetic protrusion and sepsis: case report and review of the literature. AB - Acetabular prosthetic protrusio is an unusual complication of total hip arthroplasty that develops from erosion of the medial acetabular wall and intrapelvic migration of the implant. This report reviews 3 cases of severe intrapelvic prosthetic migration where acute or chronic sepsis was associated with the condition. All subjects were female and involved the left hip. In each case, debridement of the intrapelvic implant was required with an intra-abdominal approach. After successful eradication of infection, 2 patients have a well functioning reimplanted prosthesis, and 1 was left with a Girdlestone arthroplasty. Literature review revealed that 11 of 16 similar prosthetic protrusion cases had chronic sepsis, of which, 10 were female and 9 involved the left hip. Chronic infection should be considered when intrapelvic prosthetic migration occurs after total hip arthroplasty. PMID- 17275651 TI - Extensive intrapelvic granuloma formation caused by ceramic fragments after revision total hip arthroplasty. AB - Ceramic debris embedded in a polyethylene liner was identified as the cause for rapid metal wear after revision total hip arthroplasty when a broken ceramic head was replaced by a metal head. Removal of an intrapelvic foreign body granuloma and rerevision hip arthroplasty had to be performed within 2 years after the first revision. PMID- 17275652 TI - Re: Assessment of the proximal femoral morphology using plain radiograph--can it predict the bone quality? PMID- 17275654 TI - Re: Comparison of mobile-bearing and fixed-bearing total knee arthroplasty: a prospective randomized study. PMID- 17275657 TI - Safety of rapid intravenous valproate infusion in pediatric patients. AB - In order to investigate the safety of rapidly infused intravenous valproate in children with seizures, the drug was administered to 18 patients (age range, 1-16 years) at doses ranging from 7.5 to 41.5 mg/kg and rates of 1.5 to 11 mg/kg per minute. Forty-eight intravenous valproate doses were administered during 19 hospital admissions (range, 1-16 doses per admission). Only one adverse event was reported; a 9-year-old male experienced burning at the infusion site while receiving 660 mg intravenous valproate at 6 mg/kg per minute. The patient tolerated three subsequent infusions (one of 330 mg and two of 165 mg) at the same rate with no further discomfort. Electrocardiogram results, available for 18 admissions, revealed no arrhythmias, bradycardias, or hypotensive episodes. No abnormal laboratory results were reported. Rapid intravenous valproate infusion appears to be safe in pediatric patients. PMID- 17275658 TI - A stereotypic "elbowing" movement, a possible new primitive reflex in newborns. AB - The primitive reflexes are brainstem-mediated and play various roles in the child's psychomotor development. The objective of the current study is to describe a new pattern of primitive reflex, noticed in 52 of 81 randomly chosen newborns and young infants during pressing of the subcostal region. Some of them reacted by three-phase stereotypic movement as follows: phase 1: quick adduction of upper arm with flexion of the forearm, with elbow directed toward the site of stimuli, touching the stimulated area; phase 2: abduction and retroflexion of upper arm with the movement of removing the stimulus with the elbow; phase 3: extension and pronation of the forearm. The prevalence of this newly described reflex was 64.2%. The incidence of all three phases together was highest at Day 16 (63.5%); phase 1 was the most frequent at Day 30 (88.5%) in 52 children with positive reflex. At Day 86, only 18.4% of them retained the first phase of the movement and 2% retained the third phase. All reflexes appeared until Day 30. We believe that we have described a new primitive reflex, with all characteristics essential for primitive reflexes. It is definitely involuntary, complex, stereotypic, with decreased incidence over time. Because of the defensive purpose and peculiar manner of this reflex, we named it the "elbowing reflex." PMID- 17275660 TI - Rett syndrome: clinical and electrophysiologic aspects. AB - Rett syndrome is a neurodevelopmental disorder that almost exclusively affects females. The clinical course as well as the electroencephalogram pattern are characteristic and have been correlated to the clinical stages of the disease. Sixty to 70 percent of the patients develop epilepsy. The aim of this retrospective study was to investigate the correlation between clinical stages and electroencephalogram stages and to more specifically correlate epileptic activity in electroencephalograms with the clinical symptoms of patients. The clinical development and electroencephalogram results of 11 patients diagnosed with Rett syndrome between 1 and 33 years old are compared. In 8 of 11 patients, a correlation was found between electroencephalogram stage and clinical stage. In three of them, epileptic activity in the electroencephalogram was not associated with clinical seizures. Some typical symptoms of Rett patients (hand stereotypies, vacant spells) can be difficult to differentiate from seizures. Therefore application of antiepileptic treatment should be well evaluated, as the clinical course is decisive. PMID- 17275659 TI - Evolution and treatment of childhood chronic inflammatory polyneuropathy. AB - Chronic inflammatory demyelinating polyneuropathy is a rare disease in pediatric patients. The disease usually responds well to standard therapies including immunoglobulins, corticosteroids, and plasmapheresis. However, a minority of cases appear refractory to standard treatments. This report presents the evolution of 13 patients with chronic inflammatory demyelinating polyneuropathy monitored in our pediatric neurology clinic between 1975 and 2005, including two recent patients with refractory diseases. The literature regarding treatment of refractory cases in adults and children is also reviewed. PMID- 17275656 TI - Hemorrhagic stroke in children. AB - Hemorrhagic stroke accounts for approximately half of stroke in childhood. Unlike arterial ischemic stroke, there are no consensus guidelines to assist in the evaluation and treatment of these children. This article reviews the literature on the evaluation, treatment, etiology, and neurologic outcome of hemorrhagic stroke in children. Important differences between pediatric and adult hemorrhage are highlighted, as treatment guidelines for adults may not be applicable in all cases. Required future research and potential therapies are also discussed. PMID- 17275661 TI - The impact of Pelizaeus-Merzbacher disease on the family. AB - The impact of Pelizaeus-Merzbacher disease on families and caregivers of affected children has not been well-studied. Parents, relatives, and caregivers from 18 families with 20 affected children with Pelizaeus-Merzbacher disease were asked to complete the Children's Health Questionnaire-Parent Form 50, an instrument used to assess health-related quality of life in children and family impact of illness. Mean and standard deviation (S.D.) of subscale scores were calculated and compared with previously published norms. Agreement between mothers and fathers was calculated using Cronbach's test. Mean scale scores in this cohort were lower than previously published norms for the following categories: physical function (25.9 vs 96.1, >2 S.D.); family activity (55.6 vs 89.7, >1 S.D.); and parental time impact (66.2 vs 87.8, >1 S.D.). However, family cohesion (73.3 vs 72.3, <1 S.D.), self-esteem (71.1 vs 79.8, <1 S.D.), behavior (78.9 vs 75.6, <1 S.D.), and mental health scale scores (74.2 vs 78.5, <1 S.D.) were similar to previously published norms. Parental agreement was poor, with 5 of 8 parent pairs (63%) differing in their responses (<0.7) Although impact on caregiver time and limitation of physical function and family activities is high, parents and caregivers in the cohort appear to remain cohesive and view their children's psychosocial health as similar to normal children. PMID- 17275662 TI - Sleep spindle abnormalities in children with generalized spike-wave discharges. AB - This study investigated sleep and sleep spindle parameters in children with primary generalized spike-and-wave discharges (untreated primary generalized group, nine patients; treated primary generalized group, six patients) and compared these with an age- and sex-matched nonepileptic control group (n = 47). In the untreated primary generalized group, stage 2 onset was significantly shorter, with less spindles in stage 2. In the last stage 2 period of the night, significantly less fast frequency spindles were observed, indicating abnormal dynamics of sleep architecture. In the treated group, sleep patterns were comparable to that of the control group. The data indicate sleep architecture dysfunctions in children with generalized spike-and-wave discharges. These dysfunctions could account for the frequently encountered sleep problems in children with primary generalized epilepsy. PMID- 17275663 TI - Positron emission tomography in Rasmussen's encephalitis. AB - This report presents unusual positron emission tomography findings in an 11-year old male with Rasmussen's encephalitis. This patient underwent fluorine-18 fluorodeoxyglucose positron emission tomography to localize his ictal focus before surgical consideration. Positron emission tomography disclosed marked hypermetabolism in the left cerebral hemisphere and basal ganglia with subnormal right cerebral activity and crossed cerebellar diaschisis. The heterogeneous distribution of metabolism suggests a combination of areas in different stages of ictal and postictal involvement. The hypermetabolic region in the left hemisphere was larger in size and extent (now including the left frontoparietal lobe) than the sole hypermetabolic left temporal lobe on his positron emission tomography from 2 years ago. While this positron emission tomography pattern of progression appears most commonly in Rasmussen's encephalitis case studies, few serial reports exist. The complex positron emission tomography findings of this case emphasize the importance of knowing the history of recent seizures, seizure type, clinical status at time of injection, and electroencephalographic correlation before interpreting functional neuroimaging studies. Finally, positron emission tomography studies can help clarify whether patients with Rasmussen's encephalitis with dominant hemisphere involvement are appropriate candidates for surgery or not. PMID- 17275664 TI - Myoclonic-astatic epilepsy in a child with Sturge-Weber syndrome. AB - A child with Sturge-Weber syndrome and a left occipital leptomeningeal angioma developed focal seizures at 6 years of age that responded initially to oxcarbazepine. After 7 months of seizure freedom, the patient developed typical myoclonic-astatic seizures associated with generalized electrographic discharges, which worsened as oxcarbazepine was increased. The seizures and electroencephalogram improved dramatically in 3 weeks as the oxcarbazepine was withdrawn and valproic acid was initiated. This case demonstrates the importance of recognizing that children with epilepsy due to focal lesions can develop secondary bilateral synchrony that can be aggravated by medications that are effective for partial seizures. In such cases, treatment with a broad-spectrum antiepileptic may be advantageous. PMID- 17275666 TI - Juvenile absence epilepsy exacerbated by valproic acid. AB - Valproic acid is commonly and effectively used in the treatment of idiopathic generalized epilepsies, including juvenile absence epilepsy. Although several adverse effects are associated with this drug, it has only rarely been known to exacerbate seizures. Similar to antiarrhythmic drugs aggravating particular arrhythmias, antiepileptic drugs can paradoxically induce new seizure types or exacerbate existing ones. This reaction is better known with carbamazepine and phenytoin, but is less common with broad-spectrum antiepileptic drugs such as valproic acid. This report describes a case of paradoxical, intravenous valproic acid-induced seizure exacerbation in a child with juvenile absence epilepsy, documented by video-electroencephalography. PMID- 17275665 TI - Myoclonic seizures in a patient with Charcot-Marie-tooth disease. AB - Charcot-Marie-Tooth disease affects both motor and sensory peripheral nerves, with broad variability in its clinical and pathologic expression. The involvement of the central nervous system in this disease has been reported in the past, and on two occasions Charcot-Marie-Tooth disease was associated with myoclonic seizures. The previously reported patients with associated Charcot-Marie-Tooth disease and seizures developed a severe disease and died at a young age. This report describes a now 8-year-old male with Charcot-Marie-Tooth disease type 1A associated with myoclonic seizures and developmental delay. Genetic studies established for the first time the duplication of the PMP-22 gene in a patient with this unusual association, confirming the diagnosis. The patient was treated with carbamazepine, valproate, and lamotrigine, has been seizure-free for over 2 years, and was successfully weaned from his medications. PMID- 17275667 TI - Lacunar stroke and masked hypertension in an adolescent male. AB - Hypertension has not been strongly identified as a risk factor in childhood stroke. This report describes a case of a teenager with a lacunar stroke, the type often observed in adults with hypertensive-associated infarction, and masked hypertension. The patient had normal blood pressure on initial presentation, but on further investigation demonstrated ambulatory hypertension with evidence of hypertensive end-organ damage. This case suggests that hypertension may be a risk factor in children with stroke, especially in cases of lacunar infarct. Evaluation for possible hypertension should be undertaken thoroughly to identify children who may benefit from antihypertensive therapy and therefore, prevent recurrences. PMID- 17275668 TI - Neonatal subependymal giant cell astrocytoma: new case and review of literature. AB - Subependymal giant cell astrocytomas are one of the three major intracranial lesions found in tuberous sclerosis complex. Subependymal giant cell astrocytomas are typically slow-growing tumors of mixed glioneuronal lineage which can become aggressive and cause obstructive hydrocephalus usually in older children and adolescents. Neonatal subependymal giant cell astrocytomas are extremely rare, and their natural history and prognosis are poorly understood. This report investigates an extremely large neonatal subependymal giant cell astrocytoma which was initially identified in utero at 19 weeks of gestation in a high-risk pregnancy with no family history of tuberous sclerosis complex. PMID- 17275669 TI - 3-methylcrotonyl-CoA carboxylase deficiency and severe multiple sclerosis. AB - This report describes a female with isolated 3-methylcrotonyl-CoA carboxylase deficiency. She had a mild Reye-like episode, loss of scalp hair, psychomotor retardation, and an attention-deficit hyperactivity disorder. The diagnosis was made at 13 years of age when she developed relapsing remitting multiple sclerosis with a malignant course. Treatment with steroids had initially a good therapeutic effect on the relapses. The response to interferon beta-1a treatment was poor. On mitoxantrone treatment there was a considerable neurologic recovery. PMID- 17275670 TI - Combined cyclic vomiting and Kearns-Sayre syndromes. AB - The third case of cyclic vomiting syndrome with a large mitochondrial deoxyribonucleic acid rearrangement is described. Multiple neuromuscular anomalies are present that meet the diagnostic criteria for Kearns-Sayre syndrome, as well as severe symmetrical growth retardation. A 3-kilobase mitochondrial deoxyribonucleic acid deletion (nucleotides 10970-14118) was found at 30-40% heteroplasmy in the blood of the child, but not the mother. Although mitochondrial dysfunction and disease-associated mitochondrial deoxyribonucleic acid sequence variants are believed to be present in most cyclic vomiting syndrome cases, these variants are rarely identifiable on "standard" mitochondrial deoxyribonucleic acid testing. However, finding a rearrangement has clinical implications, and standard testing is recommended in those cyclic vomiting syndrome cases with neuromuscular disease and/or growth retardation, whether maternal inheritance is present or not. PMID- 17275671 TI - Facial palsy, corticosteroids, and acute leukemia. PMID- 17275674 TI - Measurement of plasma serotonin in autism. PMID- 17275675 TI - Genetic mechanisms of susceptibility to oxidative lung injury in mice. AB - Genetic background is a known predisposing risk factor for many acute and chronic pulmonary disorders and responses to environmental oxidants. Variation in lung injury responses to oxidative stimuli such as ozone, particles, hyperoxia, and chemotherapeutic agents between genetically standardized inbred mouse strains has been demonstrated. In this review, we discuss quantitative trait loci (QTLs) which contain candidate genes that confer differential susceptibility to oxidative stimuli between strains in mouse models of airway toxicity and disease. We addressed multiple inflammatory, immunity, and antioxidant genes identified as candidate genetic determinants following these strategies, which include tumor necrosis factor (Tnf), toll-like receptor 4 (Tlr4), and the transcription factor NF-E2, related factor 2 (Nrf2). Mice with targeted deletion of these and related genes have provided initial proof of concept for their importance in the respective models. Interestingly, a few regions of the genome appear to have important roles in determining susceptibility to a number of stimuli which may suggest common genetic mechanisms in mice. Though more complete examination of functional association is required, results have potential implications for the role of these candidate genes in the pathogenesis of human pulmonary diseases including asthma, acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and emphysema. PMID- 17275677 TI - Coronary plaque injury triggers neutrophil activation in patients with coronary artery disease. AB - Activation of leukocytes, in particular polymorphonuclear neutrophils (PMN), is considered an early event in unstable coronary disease. Upon activation PMN liberate myeloperoxidase (MPO), an enzyme which binds to the vessel wall and depletes vascular NO bioavailability. Using coronary balloon angioplasty as a trigger to provoke coronary plaque injury, we assessed the time course of neutrophil activation, local and peripheral levels of myeloperoxidase, and systemic vascular NO bioavailability in patients with stable coronary artery disease. Twenty-four patients with stable CAD were enrolled prior to undergoing percutaneous interventions (PCI, n=14) and diagnostic coronary angiography (n=10), respectively. Following angioplasty arterial MPO plasma levels increased (231.5+/-67.6 to 273.8+/-80.4 pg/mg protein; P<0.01) whereas MPO levels in the coronary sinus decreased (240.8+/-74.4 vs 205.4+/-60.1 pg/mg protein; P<0.01) in the absence of elevated serum markers for myocardial necrosis. Following PCI, patients revealed impaired vascular NO bioavailability as reflected by reduced brachial flow-mediated dilation (FMD; 6.25+/-3.03 to 4.90+/-2.70%; P<0.01), whereas FMD increased in the angiography group. Coronary plaque injury provokes rapid activation of PMN in the absence of myocardial necrosis; the coronary circulation emerges as a primary site for deposition of MPO following injury of the coronary vessel wall. Activation of PMN with release of MPO is not only restricted to the target site, but can be assessed systemically and may represent a critical mechanistic link for impaired systemic vascular NO bioavailability in patients suffering unstable coronary disease. PMID- 17275676 TI - NOX5 variants are functionally active in endothelial cells. AB - NADPH oxidases have been identified as sources of reactive oxygen species (ROS) in vascular cells. In addition to the initially described enzyme containing gp91phox (NOX2), several homologues to NOX2 have been identified. Whereas NOX1, NOX2, and NOX4 are expressed in endothelial cells, a functional role of NOX5 containing additional N-terminal calcium-binding domains of varying sequences has not been reported in these cells. NOX5 protein was found in the endoplasmic reticulum of human microvascular endothelial cells (HMEC-1) and in the vascular wall. HMEC-1 cells expressed NOX5beta and NOX5delta as well as a variant lacking calcium-binding domains (NOX5S). NOX5beta and NOX5S increased basal ROS levels. Ionomycin exclusively enhanced NOX5beta-mediated ROS production. Although p22phox, when overexpressed, interacted with both NOX5 proteins, it was not essential for NOX5-mediated ROS production. NOX5 proteins stimulated endothelial cell proliferation and the formation of capillary-like structures whereas depletion of NOX5 by siRNA prevented these responses to thrombin. These data show that endothelial cells express different NOX5 variants including NOX5S lacking calcium-binding domains. NOX5 proteins are functional, promoting endothelial ROS production, proliferation, and the formation of capillary-like structures and contribute to the endothelial response to thrombin. These findings suggest that NOX5 variants play a novel role in controlling ROS-dependent processes in the vasculature. PMID- 17275678 TI - Gp91phox-containing NAD(P)H oxidase increases superoxide formation by doxorubicin and NADPH. AB - Doxorubicin is a highly effective antineoplastic drug associated with a dose dependent cardiotoxicity that may result in irreversible cardiomyopathy and heart failure. Gene variants of the superoxide-generating enzyme NAD(P)H oxidase have recently been associated with this phenotype. We investigated the mechanism of this association using lucigenin-enhanced chemiluminescence, spectrophotometry, electrochemical sensor, and electron paramagnetic resonance spectroscopy. Superoxide production was measured in female wild-type and NAD(P)H oxidase deficient (gp91phox knockout) mice. The magnitude of the increase in superoxide production on the addition of doxorubicin was much higher in hearts of wild-type mice than in enzyme-deficient mice. An increase in superoxide production was observed also on the addition of the NADPH cytochrome P450 reductase. However, doxorubicin reacted with NADPH producing superoxide even in the absence of any enzymatic activity. Taken together, gp91phox-containing NAD(P)H oxidase and NADPH cytochrome P450 reductase can enhance superoxide production caused by the chemical interaction of doxorubicin and NADPH. These findings are in agreement with the recently reported reduced cardiotoxicity following doxorubicin treatment in gp91phox knockout mice and with associations between NAD(P)H oxidase gene variants and sensitivity to doxorubicin. PMID- 17275679 TI - Parthenolide induces a distinct pattern of oxidative stress in cardiac myocytes. AB - Although parthenolide was reported to reduce cardiovascular damage in endotoxic shock and have beneficial effects in myocardial ischemia, its actions on cardiac myocytes have not been reported. Because parthenolide possesses an alpha methylene-gamma-lactone ring and epoxide residue, we hypothesized that it would induce oxidative stress in cardiac myocytes. Superoxide production and sources, viability, glutathione levels, and mitochondrial membrane potential were studied in neonatal rat ventricular myocytes treated with parthenolide. Parthenolide, dose dependently, induced oxidase activity as assessed by superoxide generation in cell lysates. Superoxide formation was increased more than 4-fold with 50 microM parthenolide. At concentrations >5 microM, parthenolide decreased cell viability in a dose-and time-dependent manner, and activated the stress MAP kinases JNK and p38. Over 6 h, parthenolide at concentrations >5 microM markedly depleted intracellular glutathione and led to collapse of the mitochondrial membrane potential. At lower parthenolide concentrations (<5 microM) the source of superoxide was mitochondria; at higher concentrations (>5 microM) the primary source was NADPH oxidase. We conclude that parthenolide causes oxidative stress in cardiac myocytes by inducing superoxide formation by mitochondrial and NADPH oxidase in a dose-dependent manner. Parthenolide may be a useful tool for studying the roles of oxidative stress and mitochondrial dysfunction in the pathogenesis of cardiac hypertrophy and failure. PMID- 17275680 TI - Antioxidant actions of nitroxyl (HNO). AB - Nitrogen oxides are endogenously produced signaling/effector molecules that have the potential to both cause and ameliorate oxidative stress. Whether nitrogen oxides behave as oxidants or antioxidants is dependent on many factors including the cellular environment, the concentration, and the presence of other reactive species. To date, the nitrogen oxide nitroxyl (HNO) has only been reported to possess prooxidant properties. However, some of its chemical properties would predict that it could also serve as an antioxidant. In this study, the possible antioxidant actions of HNO were examined using the yeast Saccharomyces cerevisiae model system. The effect of HNO on membrane lipid peroxidation was examined and HNO was determined to act solely as an antioxidant in this system. In the presence of glutathione, a thiol-containing peptide that scavenges HNO, the antioxidant action was decreased. In addition, the antioxidant properties of HNO were not due to the conversion of HNO to NO. These results were also confirmed with in vitro assays of oxidative stress. Thus, HNO has the potential to preserve lipid membrane integrity by its antioxidant actions. PMID- 17275681 TI - Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. AB - The association between iron, an oxidant catalyst, and atherosclerosis is controversial. In particular, it is unknown whether: (1) stored iron, namely serum ferritin, is correlated with catalytic iron and oxidant damage of human atherosclerotic plaques; (2) catalytic iron is related to oxidative injury within such plaques; (3) plaque oxidant burden is associated with the severity of atherosclerosis. Thus, we assessed low molecular weight iron (LMWI), which represents the metal catalytically active form, together with fluorescent damage products of lipid peroxidation (FDPL) and lipid hydroperoxides (LOOH), in 38 atherosclerotic plaques surgically removed from 38 patients who had undergone selective carotid endarterectomy. In each patient, the levels of serum ferritin were measured and correlated with those of plaque LMWI and lipoperoxides by the Spearman rank correlation test with Spearman rank correlation coefficient (r(S)) calculation. Moreover, in patients selected from the same study population, we compared plaque analyte levels between two groups with different severity of atherosclerotic carotid stenosis, i.e., <90% (group A, n = 25) or > or =90% (group B, n = 13), and between another two groups without (group C, n = 27) and with (group D, n = 11) associated contralateral carotid stenosis > or =50%, indicative of "extensive" and more severe atherosclerotic disease. In group A patients, serum ferritin was directly and significantly correlated with plaque LMWI (r(S) = 0.46, P < 0.025) and FDPL (r(S) = 0.58, P < 0.005), while its correlation with plaque LOOH, albeit direct, did not attain statistical significance. Moreover, a direct and significant relationship was evident between the plaque content of LMWI and that of both FDPL (r(S) = 0.61, P < 0.0025) and LOOH (r(S) = 0.51, P < 0.025), suggesting a prooxidant role of catalytic iron within human atherosclerotic plaques. Considering the 13 patients of group B, a positive and significant correlation was observed between the levels of serum ferritin and those of plaque LMWI (r(S) = 0.83, P < 0.0001); on the other hand, serum ferritin, as well as plaque LMWI, showed no significant correlation with either plaque FDPL or LOOH, conceivably reflecting the small number of patients belonging to group B. Finally, plaque LMWI, FDPL, and LOOH content was significantly higher in group B than in group A, and in group D than in group C. These data suggest a role for catalytic iron in atherosclerotic plaque oxidation and in the severity of atherosclerosis, which appears indeed associated with plaque oxidant burden. PMID- 17275682 TI - Mitochondrial electron transport chain activity is not involved in ultraviolet A (UVA)-induced cell death. AB - Ultraviolet A (UVA), the long wavelength part of the sun's ultraviolet radiation, elicits its harmful effects through production of reactive oxygen species. In this study, we have tested the hypothesis that the mitochondrial electron transport chain, the main source of reactive oxygen species in cells, importantly contributes to UVA-induced cell damage. Model cell lines completely lacking a mitochondrial electron transport chain (rho(0)-cells) were not protected against UVA-induced cell death. Also, primary human fibroblasts and keratinocytes with induced depletion of electron transport chain activity were not better protected against UVA-induced cell death. On the other hand, diphenyleneiodonium and resiniferatoxin, inhibitors of plasma membrane oxidases, protected primary human fibroblasts against UVA, as potently as the lipid peroxidation chain breaker Trolox. These data indicate that plasma membrane electron transport systems, but not the mitochondrial electron transport chain, play a major role in UVA-induced cell death. PMID- 17275683 TI - Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate. AB - Nitrate is abundant in our diet with particularly high levels in many vegetables. Ingested nitrate is concentrated in saliva and reduced to nitrite by bacteria in the oral cavity. We recently reported that application of nitrite-containing saliva to the gastric mucosa increases superficial blood flow and mucus generation via acid-catalyzed formation of bioactive nitrogen oxides including nitric oxide. Here we studied if dietary supplementation with nitrate would protect against gastric damage caused by a nonsteroidal anti-inflammatory drug. Rats received sodium nitrate in the drinking water for 1 week in daily doses of 0.1 or 1 mmol kg(-1). Control rats received 1 mmol kg(-1) sodium chloride. Diclofenac (30 mg kg(-1)) was then given orally and the animals were examined 4 h later. In separate experiments we studied the effects of dietary nitrate on intragastric NO levels and mucus formation. Luminal levels of NO gas were greatly increased in nitrate-fed animals. The thickness of the mucus layer increased after nitrate supplementation and gene expression of MUC6 was upregulated in the gastric mucosa. Nitrate pretreatment dose dependently and potently reduced diclofenac-induced gastric lesions. Inflammatory activity was reduced in the rats receiving nitrate as indicated by lower mucosal myeloperoxidase activity and expression of inducible NO synthase. We conclude that dietary nitrate protects against diclofenac-induced gastric ulcers likely via enhanced nitrite-dependent intragastric NO formation and concomitant stimulation of mucus formation. Future studies will reveal if a diet rich in nitrate can offer an additional nutritional approach to preventing and treating peptic ulcer disease. PMID- 17275684 TI - Hemodynamics influences vascular peroxynitrite formation: Implication for low density lipoprotein apo-B-100 nitration. AB - Hemodynamics, specifically, fluid shear stress, modulates the focal nature of atherogenesis. Superoxide anion (O2(-.)) reacts with nitric oxide (.NO) at a rapid diffusion-limited rate to form peroxynitrite (O2(-.) + .NO-->ONOO(-)). Immunohistostaining of human coronary arterial bifurcations or curvatures, where OSS develops, revealed the presence of nitrotyrosine staining, a fingerprint of peroxynitrite; whereas in straight segments, where PSS occurs, nitrotyrosine was absent. We examined vascular nitrative stress in models of oscillatory (OSS) and pulsatile shear stress (PSS). Bovine aortic endothelial cells (BAEC) were exposed to fluid shear stress that simulates arterial blood flow: (1) PSS at a mean shear stress (tau(ave)) of 23 dyn cm(-2) and a temporal gradient (partial differential(tau)/partial differential(t)) at 71 dyn cm(-2) s(-1), and (2) OSS at tau(ave) = 0.02 dyn cm(- 2) and partial differential(tau)/partial differential(t) = +/- 3.0 dyn cm(-2) s(-1) at a frequency of 1 Hz. OSS significantly up-regulated one of the NADPH oxidase subunits (NOx4) expression accompanied with an increase in O2(-.) production. In contrast, PSS up-regulated eNOS expression accompanied with .NO production (total NO(2)(-) and NO(3)(-)). To demonstrate that O2(-.) and .NO are implicated in ONOO(-) formation, we added low-density lipoprotein cholesterol (LDL) to the medium in which BAEC were exposed to the above flow conditions. The medium was analyzed for LDL apo-B-100 nitrotyrosine by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS). OSS induced higher levels of 3-nitrotyrosine, dityrosine, and o hydroxyphenylalanine compared with PSS. In the presence of ONOO(-), specific apo B-100 tyrosine residues underwent nitration in the alpha and beta helices: alpha 1 (Tyr(144)), alpha-2 (Tyr(2524)), beta-2 (Tyr(3295)), alpha-3 (Tyr(4116)), and beta-2 (Tyr(4211)). Hence, the characteristics of shear stress in the arterial bifurcations influenced the relative production of O2(-.) and .NO with an implication for ONOO(-) formation as evidenced by LDL protein nitration. PMID- 17275685 TI - Immunolocalization of hypochlorite-induced, catalase-bound free radical formation in mouse hepatocytes. AB - The establishment of oxidants as mediators of signal transduction has renewed the interest of investigators in oxidant production and metabolism. In particular, H(2)O(2) has been demonstrated to play pivotal roles in mediating cell differentiation, proliferation, and death. Intracellular concentrations of H(2)O(2) are modulated by its rate of production and its rate of decomposition by catalase and peroxidases. In inflammation and infection, some of the H(2)O(2) is converted to hypochlorous acid, a key mediator of the host immune response against pathogens. In vivo HOCl production is mediated by myeloperoxidase, which uses excess H(2)O(2) to oxidize Cl(-). Mashino and Fridovich (Biochim. Biophys. Acta 956:63-69; 1988) observed that a high excess of HOCl over catalase inactivated the enzyme by mechanisms that remain unclear. The potential relevance of this as an alternative mechanism for catalase activity control and its potential impact on H(2)O(2)-mediated signaling and HOCl production compelled us to explore in depth the HOCl-mediated catalase inactivation pathways. Here, we demonstrate that HOCl induces formation of catalase protein radicals and carbonyls, which are temporally correlated with catalase aggregation. Hypochlorite-induced catalase aggregation and free radical formation that paralleled the enzyme loss of function in vitro were also detected in mouse hepatocytes treated with the oxidant. Interestingly, the novel immuno-spin trapping technique was applied to image radical production in the cells. Indeed, in HOCl-treated hepatocytes, catalase and protein-DMPO nitrone adducts were colocalized in the cells' peroxisomes. In contrast, when hepatocytes from catalase-knockout mice were treated with hypochlorous acid, there was extensive production of free radicals in the plasma membrane. Because free radicals are short-lived species with fundamental roles in biology, the possibility of their detection and localization to cell compartments is expected to open new and stimulating research venues in the interface of chemistry, biology, and medicine. PMID- 17275687 TI - Evidence of oligonucleotides containing 8-hydroxy-2'-deoxyguanosine in human urine. AB - The product of oxidative damage to DNA, 8-hydroxy-2'-deoxyguanosine (8-OHdG), when detected in urine, is considered to be a global, noninvasive biomarker of in vivo oxidative DNA damage. In this paper we describe a novel approach to confirm the presence of oligonucleotides containing 8-OHdG in human urine. Fractions of urine were prepared by gel-filtration chromatography, and the presence of oligonucleotides was confirmed by ELISA using a monoclonal anti-(single-stranded DNA) antibody. Pools of urine fractions were subsequently prepared according to ELISA reactivity, each containing oligonucleotides with a known range of base numbers. The level of 8-OHdG in each pool was subsequently determined using a commercial ELISA kit. Results confirmed that oligonucleotides containing 8-OHdG are present in urine and, most significantly, oligomers of <30-55 bases were found to be associated with 8-OHdG. This finding strongly supports the involvement of nucleotide excision repair (NER) in the removal of 8-OHdG from the cell. The novel approach adopted in this study was validated using cell culture supernatant obtained from an in vitro model comprising CCRF cells exposed to vitamin C; this model has previously been shown to stimulate removal of 8-OHdG from the cell by an NER-dependent process. PMID- 17275686 TI - Redox regulation of the proteasome in T lymphocytes during aging. AB - Proteasome is a major cellular organelle responsible for the regulated turnover of both normal and misfolded proteins. Recent reports from our laboratory have implicated lowered proteasomal chymotryptic activity to be responsible for decreased induction of the transcription factor NFkappaB in T lymphocytes during aging. In this study, we have further analyzed the basis for this decline in proteasomal function, by focusing on the role of oxidative stress. On exposure to the prooxidant BSO, both ATP-stimulatable 26S and ATP-independent 20S proteasomal catalytic activity could be down-regulated in T cells from young donors, mimicking the decline observed in T cells from the elderly. Loss in these catalytic activities, following exposure to prooxidant stimulus, also resulted in a decline in both activation-induced proliferation and degradation of the inhibitor IkappaBalpha, with concomitant increase in the accumulation of carbonylated proteins, mimicking responses seen in T cells from the elderly. Pretreatment with an antioxidant, NAC, could override prooxidant-mediated, but not age-associated, decrease in both 20S and 26S proteasomal activities. These results suggest that the decrease in proteasomal activities observed during aging may be secondary to oxidative stress and underlie immune senescence. PMID- 17275688 TI - Zinc supplementation inhibits lipid peroxidation and the development of atherosclerosis in rabbits fed a high cholesterol diet. AB - Developing atherosclerotic lesions in hypercholesterolemic rabbits are depleted in zinc, while iron accumulates. This study examined the influence of zinc supplementation on the development of atherosclerosis and used isotope dilution gas chromatography-mass spectrometry techniques to measure biomarkers of oxidative lipid damage in atherosclerotic rabbit aorta. Our previous method for F(2)-isoprostane measurement was adapted to include the quantitation of cholesterol oxidation products in the same sample. Two groups of New Zealand white rabbits were fed a high cholesterol (1% w/w) diet and one group was also supplemented with zinc (1 g/kg) for 8 weeks. Controls were fed a normal diet. Zinc supplementation did not significantly alter the increase in total plasma cholesterol levels observed in animals fed high cholesterol. However, in cholesterol-fed animals zinc supplementation significantly reduced the accumulation of total cholesterol levels in aorta which was accompanied by a significant reduction in average aortic lesion cross-sectional areas of the animals. Elevated levels of cholesterol oxidation products (5,6-alpha and beta cholesterol epoxides, 7beta-hydroxycholesterol, 7-ketocholesterol) in aorta and total F(2)-isoprostanes in plasma and aorta of rabbits fed a cholesterol diet were significantly decreased by zinc supplementation. Our data indicate that zinc has an antiatherogenic effect, possibly due to a reduction in iron-catalyzed free radical reactions. PMID- 17275689 TI - Involvement of heat shock protein-70 in the mechanism of hydrogen peroxide induced DNA damage: the role of lysosomes and iron. AB - Heat shock protein-70 (Hsp70) is the main heat-inducible member of the 70-kDa family of chaperones that assist cells in maintaining proteins functional under stressful conditions. In the present investigation, the role of Hsp70 in the molecular mechanism of hydrogen peroxide-induced DNA damage to HeLa cells in culture was examined. Stably transfected HeLa cell lines, overexpressing or lacking Hsp70, were created by utilizing constitutive expression of plasmids containing the functional hsp70 gene or hsp70-siRNA, respectively. Compared to control cells, the Hsp70-overexpressing ones were significantly resistant to hydrogen peroxide-induced DNA damage, while Hsp70-depleted cells showed an enhanced sensitivity. In addition, the "intracellular calcein-chelatable iron pool" was determined in the presence or absence of Hsp70 and found to be related to the sensitivity of nuclear DNA to H(2)O(2). It seems likely that the main action of Hsp70, at least in this system, is exerted at the lysosomal level, by protecting the membranes of these organelles against oxidative stress-induced destabilization. Apart from shedding additional light on the mechanistic details behind the action of Hsp70 during oxidative stress, our results indicate that modulation of cellular Hsp70 may represent a way to make cancer cells more sensitive to normal host defense mechanisms or chemotherapeutic drug treatment. PMID- 17275690 TI - Conclusions about intervention effects should not be based on surrogate end points. PMID- 17275693 TI - Are they satisfied? PMID- 17275694 TI - Use of 3-dimensional color Doppler echocardiography to measure stroke volume in human beings: comparison with thermodilution. AB - BACKGROUND: The availability of accurate noninvasive measurements of cardiac output (CO) would be useful in assessing disease severity and the effects of therapeutic interventions in many different clinical settings. Current noninvasive methods are limited by their dependence on geometric assumptions. We tested the feasibility of a new technique for CO measurements based on 3 dimensional color Doppler echocardiographic (3D-CD) imaging. OBJECTIVE: We sought to compare the accuracy of CO determination in human beings as measured by 3D-CD and conventional 2-dimensional echocardiography (2DE) using thermodilution as the gold standard for comparison. METHODS: Simultaneous 3D-CD, 2DE, and thermodilution data were acquired in 47 patients postcardiac transplantation with good acoustic windows who required routine hemodynamic evaluation with a pulmonary artery catheter. Data were stored on compact disc and analyzed offline using custom software. Echocardiographic data were compared against thermodilution using linear regression and Bland-Altman analysis. RESULTS: Correlation coefficients for 3D-CD and 2DE of the left ventricular outflow tract were r = 0.94 and r = 0.78, respectively. Correlation coefficients for 3D-CD and 2DE of the mitral valve were r = 0.93 and r = 0.75, respectively. Compared with 2DE, 3D-CD demonstrated a smaller bias and narrower limits of agreement in the left ventricular outflow tract (-1.84 +/- 16.8 vs -8.6 +/- 36.2 mL) and mitral valve inflow (-0.2 +/- 15.6 vs 10.0 +/- 26 mL). CONCLUSION: The 3D-CD determination of CO is feasible and accurate. Compared with previous noninvasive modalities, 3D-CD has the advantages of independence of geometric assumptions and ease of image acquisition and analysis. PMID- 17275696 TI - Evaluation of the abdominal aorta and the renal arteries with an intracardiac echocardiography probe placed in the inferior vena cava: a feasibility study. AB - BACKGROUND: Ultrasound evaluation of the abdominal aorta and its branches is usually performed transabdominally. Not infrequently, the image quality is suboptimal. Recently, an intracardiac echocardiography probe has become commercially available. These probes are usually inserted intravenously and advanced to the right heart for diagnostic and monitoring purposes during procedures such as atrial septal defect closure and pulmonary vein isolation. Because of the close anatomic relation between the abdominal aorta and the inferior vena cava, we hypothesized that these probes would be useful in the evaluation of the abdominal aorta and the renal arteries. METHODS: Sixteen patients with normal renal function and no history of hypertension who were undergoing a pulmonary vein isolation procedure or atrial septal defect closure were studied. In each patient, the intracardiac echocardiography probe was inserted in the femoral vein and advanced to the right atrium for the evaluation of the left atrium and the pulmonary veins during the procedure. At the end of the therapeutic procedure, the probe was withdrawn into the inferior vena cava for the evaluation of the aorta and renal arteries. RESULTS: High-resolution images of the abdominal aorta from the diaphragm to its bifurcation were easily obtained in all patients. These images allowed for the evaluation of arterial size, shape, and blood flow. Both renal arteries were easily visualized in each patient. With the probe in the inferior vena cava, both renal arteries were parallel to the imaging plane and, therefore, accurate measurement of renal blood flow velocity and individual renal blood flow were measured. PMID- 17275695 TI - Noninvasive assessment of coronary vasodilating capacity using freehand 3 dimensional echocardiography with rotational scanning. AB - BACKGROUND: Noninvasive measurement of coronary vasomotion is important for the evaluation of patients with coronary artery disease (CAD). We tested the possibility of the assessment of epicardial coronary artery vasodilating capacity using freehand 3-dimensional (3D) echocardiography. METHODS: In 45 individuals (29 control subjects [age 51 +/- 12 years, male:female = 14:15; control group] with normal coronary angiogram and 16 patients with multivessel CAD ([age 60 +/- 12 years, male:female = 9:7; CAD group]), using a 3D echocardiography unit with magnetic tracking system linked to the conventional 2-dimensional ultrasound system, 3D echocardiography image acquisition and reconstruction of the distal left anterior descending coronary artery (LAD) flow were performed before and after sublingual nitroglycerin administration (0.6 mg). Quantitative analysis of coronary vasodilation was performed on cross-sectional 3D images and was compared with the mean diameter of the distal LAD by quantitative coronary angiography. RESULTS: The distal LAD diameter on coronary 3D increased from 2.28 +/- 0.79 to 3.32 +/- 1.07 mm (52.3 +/- 28.5%) in control group and from 2.36 +/- 0.65 to 2.89 +/- 0.81 mm (23.7 +/- 23.9%) in CAD group after nitroglycerin administration (P < .005 vs control group). The cut surface diameter of the 3D LAD flow was 2.17 +/- 0.34 mm and the mean diameter using quantitative coronary angiography was 1.99 +/ 0.28 mm. There was a good correlation between baseline diameter of 3D image and mean quantitative coronary angiography data (R = 0.673, P < .005). CONCLUSION: The vasodilation after nitroglycerin administration is reduced in advanced atherosclerosis and can be noninvasively measured. The 3D reconstruction of the distal LAD flow is a promising noninvasive technique to study coronary vasomotor function. PMID- 17275698 TI - High-resolution myocardial perfusion imaging in mice with high-frequency echocardiographic detection of a depot contrast agent. AB - High-resolution methods for assessing myocardial perfusion in murine models of cardiovascular disease are needed. We hypothesized that regional hypoperfusion could be assessed with ultrahigh-frequency myocardial contrast echocardiography (MCE) and a novel strategy of depot contrast enhancement. MCE was performed with 30-MHz transthoracic imaging 10 seconds and 10 minutes after intravenous administration of microbubbles in control mice, and in mice after left anterior descending coronary artery ligation. MCE was also performed using size-segregated microbubbles. Microbubble behavior in the microcirculation was evaluated with intravital microscopy. In control mice anterior myocardial enhancement was robust at 10 seconds, but left ventricular cavity attenuation precluded evaluation of posterior segments. After 10 minutes, left ventricular cavity signal cleared but myocardial enhancement persisted, permitting analysis of all segments. The degree of enhancement at 10 min was related to microbubble size, implying retention of large microbubbles transiting pulmonary arteriovenous shunts. Intravital microscopy confirmed capillary lodging of large microbubbles. Infarct size by delayed MCE correlated with fluorescent nanospheres (r = 0.94, P < .001). We conclude that complete assessment of regional myocardial perfusion in the mouse heart is possible with high-frequency MCE and a single intravenous contrast agent injection. This technique can be used for characterizing murine models of myocardial infarction and left ventricular remodeling. PMID- 17275697 TI - Determination of size and transmural extent of acute myocardial infarction by real-time myocardial perfusion echocardiography: a comparison with magnetic resonance imaging. AB - OBJECTIVE: The exact determination of acute myocardial infarction (AMI) extent is still a challenging issue. Quantitative myocardial perfusion echocardiography (MPE) with parametric imaging (PI) and gray scale (GS) has been shown to accurately measure infarcted area in animals, but not in human beings. We sought to validate MPE quantification of transmural extent and size of AMI using magnetic resonance imaging (MRI) as a gold standard. METHODS: Twenty patients (12 men, 64 +/- 13 years) underwent MPE and MRI between the second and fifth day post AMI. Infarct area and location, number of involved segments, and transmural extent in each segment were determined by PI using beta value and GS. Results were compared with late enhanced MRI. RESULTS: There was 99% agreement between both methods regarding the segmental location. The correlation between infarct area by MRI and GS was 0.82 (P < .001) whereas MRI and beta PI was 0.92 (P < .001). The correlation between transmural extent by MRI and GS was 0.77 (P < .001), and between MRI and beta PI was 0.93 (P < .001). CONCLUSION: There was a good correlation between MPE, in special beta PI, with MRI in measuring infarcted area and its transmural extent in patients with AMI. PMID- 17275699 TI - Extent of right and left ventricular focal wall-motion abnormalities in differentiating transient apical ballooning syndrome from apical dysfunction as a result of coronary artery disease. AB - Differentiating the ventricular dysfunction caused by apical ballooning syndrome (ABS) from that caused by apical involvement in an acute coronary syndrome (ACS) currently requires coronary angiography. We sought to determine if echocardiography could differentiate these two syndromes by the extent of regional left ventricular (LV) and right ventricular (RV) dysfunction. The location of the hinge point between normal and hypokinetic wall motion for both the RV and LV was blindly determined in 8 patients with ABS and in 16 patients with an initial ACS secondary to obstruction of the left anterior descending coronary artery and an associated apical wall-motion abnormality. The hinge point for each wall was expressed as the percent of the wall from the apex to the annulus that was akinetic and determined for the RV free wall, the interventricular septum, and the LV anterior, inferior, and lateral walls. The ABS group as compared with the ACS group had a significantly greater RV involvement (48 +/- 20% vs 7.3 +/- 15%, P < .0001) and LV lateral wall involvement (53 +/- 18% vs 34 +/- 11%, P = .005). However, there were no differences between these groups for the other LV walls. An RV hinge point 40% from the apex was exceeded in 7 of 8 patients with ABS but in only 1 of 13 patients with ACS (P = .0005). In conclusion, patients with ABS had significantly greater RV free wall and LV lateral wall dysfunction as compared with patients with ACS. This pattern of wall-motion abnormalities, when present, could allow for an early presumptive and noninvasive diagnosis of ABS. PMID- 17275700 TI - Strain rate imaging differentiates hypertensive cardiac hypertrophy from physiologic cardiac hypertrophy (athlete's heart). AB - BACKGROUND: This study sought to determine whether strain rate imaging could distinguish between individuals with hypertensive left ventricular hypertrophy (LVH) and those with strength-training athletic LVH. METHODS: In all, 108 participants (30 hypertensive LVH, 30 strength-training LVH, 48 control) were enrolled. In addition to a baseline echocardiogram, strain, peak systolic strain rate (SR(S)), peak early diastolic strain rate (SR(E)), and peak late diastolic strain rate values were compared in the apical 4-chamber view. RESULTS: Athletes had no significant differences in strain, SR(S), SR(E), or peak late diastolic strain rate compared with control subjects (P = .11, .99, .85, and .09, respectively). Individuals with hypertensive LVH had significantly decreased strain, SR(S), and SR(E) (-16.8 +/- 3.2%, -0.99 +/- 0.15 s(-1), and 1.54 +/- 0.40 s(-1), respectively) compared with control subjects (-21.7 +/- 3.5%, -1.31 +/- 0.27 s(-1), and 2.35 +/- 0.57 s(-1), respectively; all P < .0001). CONCLUSION: Hypertensive LVH has significant longitudinal strain, SR(S), and SR(E) reductions versus control. The lack of these reductions in athletes suggests that strain rate imaging may have clinical use in discerning the physiologic LVH state. PMID- 17275701 TI - Positive isovolumic relaxation velocity detected by a spectral tissue Doppler mapping technique as an indicator of coronary artery disease: a prospective study. AB - BACKGROUND: A positive myocardial velocity during isovolumic relaxation phase (V(IR)) detected by spectral tissue Doppler imaging has been shown to indicate ischemic myocardium. We sought to examine the diagnostic value of positive V(IR) for detecting coronary artery disease (CAD) in patients with chest pain and apparently normal left ventricular contraction. METHODS: A total of 138 patients (74 men, age 69 +/- 8 years) underwent spectral Doppler tissue imaging measurements at the annular and mid left ventricular levels in the apical 4- and 2-chamber views (8 points/patient) at rest in addition to standard echocardiography. Subsequently, patients underwent thallium-201 myocardial perfusion single photon emission computed tomography (n = 98) and/or coronary angiography (n = 60). The duration of positive V(IR) was also assessed. CAD was diagnosed by having more than 75% diameter stenosis in coronary angiography. RESULTS: CAD was present in 41 patients (30%). The duration of positive V(IR) was distributed from 0 to 280 milliseconds with the median value of 100 milliseconds. Presence of positive V(IR) predicted CAD with sensitivity of 80% and specificity of 61%. CONCLUSIONS: Positive V(IR) detected by spectral tissue Doppler imaging is a useful indicator of CAD in patients with apparently normal left ventricular contraction and chest pain. PMID- 17275702 TI - High spatial resolution speckle tracking improves accuracy of 2-dimensional strain measurements: an update on a new method in functional echocardiography. AB - BACKGROUND: We previously found that a 2-dimensional (2D) strain echocardiography method had some limitations in the assessment of low magnitudes and rates of deformation. Here, we study whether a recently introduced high spatial resolution speckle tracking (HRT) method improves accuracy of 2D strain measurements. METHODS: A gelatin block was cyclically compressed by a hydraulic piston. Regional deformations measured by 2D-HRT were compared with reference strains obtained from an embedded pair of sonomicrometry crystals. Global deformations (along the gelatin block) were compared to strains calculated from tracings of piston motion. We tested a wide range of strains (5.4%-21.5%) and combined each measurement with simulated heart rates (24-196/min). RESULTS: Regional deformations measured by 2D-HRT demonstrated excellent correlation (r = 0.99, P < .0001) and agreement (bias +/- 2SD = -0.3 +/- 1.3%) with sonomicrometry. Close correlation (r = 0.99, P < .0001) and agreement (bias +/- 2SD = 0.5 +/- 1.2%) was observed also for global strains measured by 2D-HRT and compared with tracings of piston motion. There was good reproducibility of all tests: interobserver and intraobserver variabilities were 3.2% and 3.4% for regional strains and 3.1% and 3.5% for global strains, respectively. CONCLUSION: In our in vitro setting, the 2D-HRT method produced precise and accurate measurements of strains for clinically relevant ranges of deformation magnitudes and ranges. PMID- 17275703 TI - Hemodynamic effects of tachycardia in patients with relaxation abnormality: abnormal stroke volume response as an overlooked mechanism of dyspnea associated with tachycardia in diastolic heart failure. AB - BACKGROUND: Prevention of tachycardia is an important therapeutic strategy in patients with relaxation abnormality. METHODS: Eleven patients with stable relaxation abnormality (group 1) and 8 healthy individuals (group 2) were enrolled. Left ventricular (LV) mean diastolic pressure, LV dimensions, stroke volume (SV), and LV ejection, filling, and isovolumic times between right atrial pacing rates of 80 and 120/min were compared. RESULTS: Both groups 1 and 2 showed significant decreases in LV mean diastolic pressure when heart rate (HR) increased. At a HR of 80/min, no significant difference was noted between groups 1 and 2 in SV (51.4 +/- 13.0 vs 45.2 +/- 9.0 mL, P = .35). However, a decrement in SV between a HR of 80 and 120/min was significantly greater for group 1. Therefore, group 1 showed a significantly lower SV (30.2 +/- 7.1 vs 40.1 +/- 6.9 mL, P < .05) at a HR of 120/min. In terms of time intervals between HRs of 80 and 120/min, group 1 showed a significantly greater reduction in LV ejection time (84.5 +/- 20.1 vs 30.0 +/- 34.6 milliseconds, P < .005) and a smaller reduction in LV filling time (106.4 +/- 38.5 vs 166.3 +/- 30.7 milliseconds, P < .005) than group 2. CONCLUSIONS: Results of our study suggest that an inadequate SV response to tachycardia may play an important role in the production of dyspnea associated with tachycardia in these patients. PMID- 17275704 TI - Left atrial remodeling in patients younger than 70 years with diastolic and systolic heart failure. AB - OBJECTIVE: We sought to determine left atrial (LA) volume and systolic function (LA remodeling) in younger (<70 years) patients with systolic and diastolic heart failure (HF). METHODS: In all, 32 patients with diastolic HF (left ventricular [LV] ejection fraction > or = 0.50), 26 patients with systolic HF (LV ejection fraction < 0.50), and 48 control subjects were studied. LAlpha volume (cm(3)/m(2)) was echocardiographically determined at mitral valve opening (maximal), mitral valve closure (minimal), and atrial systole (electrocardiographic Rho wave) using the biplane area-length method. The LA active emptying fraction (%) and ejection force (kdyne/m(2)) served as indices of LA systolic function. RESULTS: LA maximal volume was greater in systolic HF than diastolic HF and in the latter greater than control (68.6 +/- 13.8 vs 52 +/- 11.6 vs 42.9 +/- 14.4, respectively, P < .0001). Active emptying fraction was similar between diastolic HF and control, and greater than systolic HF (31.5 +/- 8.1 vs 36.3 +/- 7 vs 26.6 +/- 6.2, respectively, P < .0001), whereas LA ejection force was similar in diastolic and systolic HF and greater than control (5.05 +/- 1.3 vs 4.98 +/- 2.17 vs 3.63 +/- 2.05, respectively, P = .001). Vmax was related to body surface area, brain natriuretic peptide, and LV mass in diastolic HF (multiple R2 = 0.74) and to diastolic blood pressure, LV mass, and early to late transmitral flow velocity ratio in systolic HF (multiple R2 = 0.96). CONCLUSIONS: LA remodeling is more severe in systolic HF than diastolic HF and governed by different mechanisms. This may be of significant clinical relevance regarding the morbidity and mortality of these two conditions. PMID- 17275706 TI - Prevalence and clinical correlates of mitral annulus calcification in Hispanics and non-Hispanic whites. AB - BACKGROUND: Data about mitral annulus calcification (MAC) are sparse in Hispanics. We compare prevalence and clinical correlates of MAC in Hispanics and non-Hispanic whites. METHODS: We reviewed echocardiograms and clinical data of 337 Hispanics and 279 non-Hispanic whites, age 45 to 75 years. In cross-sectional data, prevalence and interrelationships of MAC, coronary heart disease (CHD), and risk factors were compared using multivariable logistic regression. RESULTS: In Hispanics, MAC was significantly associated with CHD (odds ratio [OR] = 2.06, confidence interval [CI] = 1.09-3.87), age (OR = 1.73, CI = 1.21-2.49), female sex (OR = 1.87, CI = 1.01-3.47), smoking (OR = 1.80, CI = 1.01-3.24), and having multiple (>2) risk factors (OR = 3.43, CI = 2.66-4.43). In non-Hispanic whites, MAC was associated with CHD (OR = 4.24, CI = 2.00-8.98), age (OR = 2.87, CI = 1.82-4.50), and having multiple risk factors (OR = 3.59, CI = 2.7-4.77). There were no significant ethnic differences in prevalence of MAC. CONCLUSIONS: Among Hispanics referred for echocardiography, MAC is associated with CHD and risk factors. PMID- 17275705 TI - Noninvasive assessment of pulmonary arterial capacitance by echocardiography. AB - BACKGROUND: Pulmonary arterial capacitance (PAC) has been associated with right ventricular (RV) workload and mortality in pulmonary hypertension, but is not routinely evaluated in children. We investigated whether PAC can be estimated noninvasively by echocardiography. METHODS: We retrospectively determined PAC in 31 children with pulmonary hypertension, using echocardiography, and compared the results with those obtained at cardiac catheterization. RESULTS: PAC derived from echocardiography was similar to that derived from catheterization (mean +/- SD 1.16 +/- 1.0 vs 1.10 +/- 0.95 mL(3) x mm Hg(-1), P = not significant) and the two correlated well (r = 0.74, P < .0001). There was a highly significant polynomial relationship between PAC and RV anterior wall thickness indexed to body surface area (R(2) = 0.54, P < .0001), but not between pulmonary vascular resistance and RV wall thickness. Pulmonary vascular resistance and PAC did not correlate. CONCLUSIONS: Echocardiography can reliably estimate PAC, which strongly correlates with RV hypertrophy, a surrogate for RV work. PMID- 17275707 TI - Biatrial primary synovial sarcoma of the heart. AB - Synovial sarcomas that primarily arise from the heart and pericardium are extremely rare, especially the ones involving both sides of the heart. To date, few cases have been reviewed in the literature. Our patient was a 36-year-old man who presented with primary biatrial synovial sarcoma that also involved the tricuspid annulus, heart valves, and interatrial septum. The tumor was debulked to relieve the atrioventricular obstruction. Molecular analysis confirmed the diagnosis of synovial sarcoma with positive t (X;18) SYT-SSX gene fusion. The patient is currently receiving chemotherapy. From our review of the 20 cases thus far reported in the English-language medical literature, the tumor more frequently affects young male patients, and carries a poor prognosis. Early detection is difficult because of the aggressive nature of the tumor. Like other sarcomas, wide surgical resection remains the mainstay of therapy. Adjuvant radiation therapy for local recurrence and chemotherapy for control of systemic disease may have some beneficial effect on overall survival, but the benefit is likely limited. PMID- 17275708 TI - A rare cause of pericardial constriction in a young man. PMID- 17275709 TI - Prominent crista terminalis: as an anatomic structure leading to atrial arrhythmias and mimicking right atrial mass. AB - Crista terminalis is a fibromuscular ridge at the posterolateral region of the right atrium (RA). Superiorly localized prominent crista terminalis can mimic pathologic RA mass on transthoracic echocardiograms. Transesophageal echocardiography can be used to differentiate nonpathologic structures from pathologic ones. Besides mimicking RA mass, crista terminalis is an important anatomic structure responsible for paroxysmal atrial fibrillation and atrial flutter by initiating ectopic atrial beats. In this case we discuss a patient with atrial arrhythmias who had prominent crista terminalis misdiagnosed as RA mass. PMID- 17275710 TI - Contrast echocardiographic imaging of left ventricular diverticulum in adult patients. PMID- 17275711 TI - A case of traumatic tricuspid valve regurgitation caused by blunt chest trauma. AB - A case of severe tricuspid valve regurgitation caused by ruptured chordae tendineae secondary to blunt chest trauma from a motor vehicle accident is described. A transthoracic echocardiogram did not demonstrate these findings, which were clearly visualized on a transesophageal echocardiogram. We propose that patients with blunt chest trauma be considered for transesophageal echocardiography (unless surface images are of high quality) to evaluate not only the tricuspid valve apparatus but to examine other cardiac structures as early (ie, presymptomatic) treatment is preferable. PMID- 17275712 TI - Right ventricular tissue Doppler parameters in a patient with massive pulmonary embolus. AB - We present right ventricular tissue Doppler findings in a 41-year-old man with pelvic fracture who had a near-fatal pulmonary embolus. We found small early systolic lengthening and reduced delayed systolic shortening using strain and strain rate imaging. There were also delayed and fused diastolic waves. Normal systolic tricuspid annular velocities were absent and there was only one late tricuspid annular ascent velocity. Strain, strain rate, and tricuspid annular velocities were normalized early after surgical embolectomy. PMID- 17275713 TI - Diastolic function: a sonographer's approach to the essential echocardiographic measurements of left ventricular diastolic function. AB - Noninvasive assessment of left ventricular filling pressures by echocardiography has been validated by invasive hemodynamic studies and correlated with clinical findings. A comprehensive echocardiographic examination based on the referral diagnosis and patient symptomatology routinely includes efforts to measure specific parameters of left ventricular diastolic function. We provide a step-by step approach to goal-directed echocardiographic assessment of diastolic function. PMID- 17275714 TI - About left atrial enlargement in dilated cardiomyopathy. PMID- 17275715 TI - Response to: "Double atrial septum with persistent interatrial space: echocardiographic features of a rare atrial septal malformation". PMID- 17275716 TI - Effectively managing antiretroviral therapy: innovative insights for improving patient outcomes. PMID- 17275717 TI - Current clinical issues impacting the lives of patients living with HIV/AIDS. AB - By significantly delaying the onset of AIDS, highly active antiretroviral therapy (HAART) decreases the high rates of mortality and morbidity previously associated with HIV type 1 infection. However, to gain the therapeutic benefits of HAART, patients must commit to lifelong therapy, which carries an increased risk of multiple metabolic comorbidities, including dyslipidemia and hyperglycemia. Hyperlipidemia associated with HAART can be accompanied by abnormal accumulation of adipose tissue in the abdominal and dorsocervical regions, collectively known as lipodystrophy. Additionally, hyperglycemia associated with HAART causes development of type 2 diabetes mellitus. Moreover, patients experiencing adverse metabolic effects associated with HAART have an increased risk for developing cardiovascular disease. Currently, metabolic comorbidities in patients infected with HIV are managed by interventional pharmacotherapy. However, because HAART regimens already have such high pill burdens, treatment of comorbidities with additional drugs may lead to nonadherence. This article will review the differential metabolic effects of various HAART regimens and the clinical implications for patients living with HIV/AIDS. PMID- 17275718 TI - Strategies for improving patient adherence to therapy and long-term patient outcomes. AB - Adherence to treatment regimens is essential to the success of highly active antiretroviral therapy (HAART) in patients infected with HIV. Multiple research studies have clearly demonstrated the close association between proper adherence to HAART and decreases in both plasma HIV RNA levels and HIV-associated mortality rates. In an effort to maintain virologic suppression, adherence levels of 95% are required for patients treated with HAART. However, community reports suggest that actual adherence levels are often far lower than those required for successful HAART; many studies show that 40% to 60% of patients are less than 90% adherent. Multiple reasons for nonadherence to HAART regimens have been reported by patients infected with HIV. Patients with mental illness (e.g., depression) are more than seven times more likely not to adhere to HAART regimens compared with patients without mental illness. Substance abuse is also a major barrier to adherence, with approximately 66% of HIV-infected intravenous drug users reporting suboptimal adherence to HAART regimens. Other barriers to adherence include uncertainty about both the effectiveness of treatment and the consequences of poor adherence, regimen complexity, side effects of treatment, and lack of social support. This article will discuss the strategies that should be used by all members of the multidisciplinary team treating patients with HIV/AIDS to encourage patient adherence to treatment. These strategies include educating and motivating patients, simplifying treatment regimens and tailoring them to individual lifestyles, preparing for and managing side effects, and addressing the concrete issues that may present barriers to adherence. In addition, adherence-boosting interventions that have established efficacy in controlled trials, such as motivational interviewing, and nurse-based interventions for patient populations with low health-literacy will be reviewed. PMID- 17275719 TI - Long-Term suppression of HIV infection: benefits and limitations of current treatment options. AB - HIV type 1, a causative agent of AIDS, is a source of worldwide morbidity and mortality. There are an estimated 1 million people in North America currently living with HIV infection, and more than 40,000 new cases occur annually. Before the advent of highly active antiretroviral therapy (HAART), the mortality rate of HIV infection was nearly 100%, and life expectancy was short. However, successful HAART delays the onset of AIDS, allowing patients to live with chronic HIV infection for 20 years or more. HAART usually consists of a combination of protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs). Although these agents are highly efficacious in delaying the onset of AIDS, their clinical utility is limited by viral resistance, nonadherence to therapy, and drug toxicity. Consequently, multidrug regimens are necessary for successful treatment. Initial NNRTI-based HAART regimens are effective at reducing viral load and boosting CD4(+) cell counts. NNRTI resistance is uncommon, but should it occur, the NNRTI-based therapy needs to be quickly replaced by a PI-based therapy. Triple NRTI-based regimens are recommended only if NNRTI- or PI-based regimens cannot be used. When developing a multidrug regimen, it is also important to select HAART agents with limited adverse effects. Because each HAART agent has its own unique adverse effect profile, selecting a regimen with a favorable profile may be difficult. For example, certain PIs produce adverse metabolic effects that may increase the risk of developing cardiovascular disease. In contrast, NNRTI-based therapies have a different side effect profile. Because each HAART agent has specific limitations, tailoring a regimen to the individual patient is of paramount importance for achieving optimal outcomes. PMID- 17275720 TI - Diversity in practice. PMID- 17275721 TI - Pollio's approach to existential phenomenology: A brief synopsis. PMID- 17275722 TI - The perianesthesia experience from the patient's perspective. AB - The purpose of this study was to investigate the perianesthesia experience from the patient's perspective. An existential phenomenological approach using Pollio's interpretive framework was used. Interpretations were conducted, in part, in a research group. The purpose of the interpretation was to recognize patterns or themes in an experience. Participants were asked to describe specific experiences that stood out for them because experiences which stand out are those that are meaningful. Ten participants (5 males, 5 females) ranging in age from 23 to 66 years were interviewed using phenomenological techniques. The interpretation found the perianesthesia experience to be grounded in self, others, and time, which become figural through experiences of control. Each participant relinquished control, lost control, or strove to gain or maintain control during their surgical experience. The perception of death lurking crossed into figural experiences as well. Images of death, while grouped predominantly with self, were interpreted as the ultimate loss of self, others, and time. Loss of control of self, the relinquishing of control to others, and the temporal experience of control may contribute to perianesthesia stress and anxiety. Nurses in the perianesthesia period have many opportunities to help patients with issues of control. PMID- 17275723 TI - Participation in and satisfaction with perianesthesia continuous professional development. AB - A descriptive correlational study was designed to evaluate ASPAN's continuing professional development (CPD) offerings by determining the modalities that ASPAN members use to obtain specialized perianesthesia education and their level of satisfaction with these offerings. An electronic survey developed by the researchers was used to query members of ASPAN with active email addresses. Participation in CPD offered by ASPAN varies considerably by modality. The respondents in this study preferred and were most satisfied with traditional delivery systems of lecture/seminar that provided clinical information. Participants were also sensitive to cost and location. PMID- 17275724 TI - Sensorineural hearing changes after myelogram. AB - Dire consequences can occur after any medical or surgical procedure. Certain procedures may even cause sensorineural hearing loss (SNHL). Previous studies have demonstrated that certain surgical and medical procedures may result in hearing losses of varying degrees. Although hearing loss is a well-known phenomenon, little consistent information exists about hearing loss after medical or surgical procedures. This one-tailed, directional study compared the effect of myelogram procedures on hearing in selected outpatients. A pre/posttest design was used to measure audiograms in 27 myelogram subjects. Pre- and postprocedure hearing tests were measured by audiometry and compared for differences. Results did not support previous studies that low-frequency hearing loss can occur within 24 hours after myelogram procedure. Clinically relevant information was found in one subject 53 hours post myelogram. PMID- 17275726 TI - With CAD, faster is never better. PMID- 17275725 TI - A comprehensive medication management program in the ambulatory surgery setting. PMID- 17275727 TI - Statistics 101 in research (part 1 of 3 series). PMID- 17275729 TI - Where is the optimism? Warrior teachings to regain the drug discovery spirit. PMID- 17275730 TI - Biotechnology in Ireland: hard work, money and the brain gain. PMID- 17275731 TI - Targeting mammalian target of rapamycin (mTOR) for health and diseases. AB - The macrolide rapamycin is used clinically to treat graft rejection and restenosis. Mammalian target of rapamycin (mTOR) is a central controller of cellular and organism growth that integrates nutrient and hormonal signals, and regulates diverse cellular processes. New studies have linked mTOR to several human diseases including cancer, diabetes, obesity, cardiovascular diseases and neurological disorders. Recent data have also revealed that mTOR is involved in the regulation of lifespan and in age-related diseases. These findings demonstrate the importance of growth control in the pathology of major diseases and overall human health, and underscore the therapeutic potential of the mTOR pathway. PMID- 17275732 TI - Potential role of pharmacogenetics in anti-TNF treatment of rheumatoid arthritis and Crohn's disease. AB - Etanercept, infliximab and adalimumab have shown clinical benefit in immune mediated inflammatory diseases; however, the outcome of treatment with these tumour-necrosis factor inhibitors remains insufficient in approximately 40-60% and approximately 25-40% of individuals with rheumatoid arthritis and Crohn's disease, respectively. Moreover, their use is accompanied by adverse events and unintentional immune suppression. Pharmacogenetics has the potential to increase efficacy and ameliorate adverse events and immune suppression, and its application might be of clinical benefit for patients with rheumatoid arthritis and Crohn's disease. Pharmacogenetic studies have shown associations between single nucleotide polymorphisms in genes encoding enzymes related to the pharmacodynamics of these drugs and treatment outcome. As we discuss here, replication and prospective validation are warranted before pharmacogenetics can be used in clinical practice. PMID- 17275734 TI - In silico selection of active siRNA. AB - RNA interference (RNAi) mediated by short interfering RNA (siRNA) represents a powerful reverse genetics tool, and siRNAs are attracting increasing interest as potential therapeutics. Progress in the design of functional siRNAs has significantly contributed to our understanding of cellular RNA silencing pathways and vice versa. Parameters related to RNA sequence and structure have a strong impact on various steps along the silencing pathway and build the backbone of many siRNA design tools. Recent work has demonstrated that there is more to siRNA design than enhancement of gene silencing activity. Current efforts aim at avoidance of off-target effects, the understanding of siRNA-triggered immunostimulation, and evasion of interference with cellular regulatory RNA. Molecular features determining the biological functions of siRNA and their meaning for computational (in silico) selection are the focus of this review. PMID- 17275735 TI - Scaffold selection and scaffold hopping in lead generation: a medicinal chemistry perspective. AB - Hit selection and lead generation are crucial for the success of the resource demanding lead-optimization phase in drug discovery, and represent a major research area of medicinal chemistry today. Ligand-binding efficiency, ligand complexity, ligand-target profile complementarity and chemical tractability are important parameters in hit selection. As synthesis and assay throughput improve, a large number of analogs based on the same scaffold can be rapidly synthesized and tested. Consequently, more chemistry resources could be devoted to scaffold modifications to expand the candidate pool in lead generation. Most recently discovered druggable targets are promiscuous toward lipophilic ligands, and the hydrophobic portions of hit compounds should be preferentially modified in analog and scaffold design. PMID- 17275733 TI - Targeting structural flexibility in HIV-1 protease inhibitor binding. AB - HIV-1 protease remains an important anti-AIDS drug target. Although it has been known that ligand binding induces large conformational changes in the protease, the dynamic aspects of binding have been largely ignored. Several computational models describing protease dynamics have been reported recently. These have reproduced experimental observations, and have also explained how ligands gain access to the binding site through dynamic behavior of the protease. Specifically, the transitions between three different conformations of the protein have been modeled in atomic detail. Two of these forms were determined by crystallography, and the third was implied by NMR experiments. Based on these computational models, it has been suggested that binding of inhibitors in allosteric sites might affect protease flexibility and disrupt its function. PMID- 17275736 TI - Fragments, network biology and designing multiple ligands. AB - Modulating multiple protein targets simultaneously can be beneficial for treating complex diseases. The redundancy that exists within biological networks means that modulating single proteins might not be sufficient to produce the desired efficacy while, at the same time, minimizing adverse effects. Designing multi target drugs can be challenging for medicinal chemists, with current lead discovery strategies often producing large, complex molecules with low ligand efficiency and poor oral bioavailability. Paradoxically, analyses of the relationship between the selectivity of biologically active compounds and their molecular size suggest that promiscuous compounds should typically be smaller than target-selective compounds. A fragment-based approach to multi-target drug discovery could lead to a new generation of compounds with improved physicochemical and pharmacokinetic properties. PMID- 17275737 TI - Treating desires not diseases: a pill for every ill and an ill for every pill? PMID- 17275738 TI - Disease induction by human microbial pathogens in plant-model systems: potential, problems and prospects. AB - Relatively simple eukaryotic model organisms such as the genetic model weed plant Arabidopsis thaliana possess an innate immune system that shares important similarities with its mammalian counterpart. In fact, some human pathogens infect Arabidopsis and cause overt disease with human symptomology. In such cases, decisive elements of the plant's immune system are likely to be targeted by the same microbial factors that are necessary for causing disease in humans. These similarities can be exploited to identify elementary microbial pathogenicity factors and their corresponding targets in a green host. This circumvents important cost aspects that often frustrate studies in humans or animal models and, in addition, results in facile ethical clearance. PMID- 17275739 TI - Global clinical data interchange standards are here! AB - The Clinical Data Interchange Standards Consortium (CDISC) has succeeded in developing global clinical data interchange standards that are ready for implementation. The various CDISC models are identified and explained in this article as well as how these models work together. In addition to developing the CDISC standards, CDISC is involved actively in many collaborative projects with other organizations as a result of their numerous alliances and partnerships. CDISC standards are supporting not only the pharmaceutical industry but also other initiatives and services in healthcare. PMID- 17275742 TI - Recent advances in Oral Oncology. AB - This paper reviews the main papers related to oral squamous cell carcinoma published in 2006 in oral oncology - an international interdisciplinary journal which publishes high quality original research, clinical trials and review articles, and all other scientific articles relating to the aetiopathogenesis, epidemiology, prevention, clinical features, diagnosis, treatment and management of patients with neoplasms in the head and neck, and orofacial disease in patients with malignant disease. PMID- 17275744 TI - Increased impedance to inspiration ameliorates hemodynamic changes associated with movement to upright posture in orthostatic hypotension: a randomized blinded pilot study. AB - BACKGROUND: Movement to upright posture may result in marked drop of blood pressure with susceptibility to injury from syncope and falls in patients with orthostatic hypotension. OBJECTIVE: The purpose of this study was to determine if increasing negative intrathoracic pressure by using an inspiratory impedance threshold device before change of posture diminishes blood pressure fall by enhancing venous return. METHODS: Eighteen healthy subjects and 22 orthostatic hypotension patients were randomized to either an active (impedance 7 cmH2O) or sham (no inspiratory impedance) impedance threshold device. Arterial blood pressure, heart rate, and estimated stroke volume and total peripheral resistance were recorded in the supine and upright postures using a noninvasive finger arterial blood pressure monitor. After a rest period, the alternate impedance threshold device (sham or active) was tested in each individual. RESULTS: Compared with the sham impedance threshold device test, the active impedance threshold device resulted in significant reduction in the magnitude of upright posture-induced fall in blood pressure and a greater increase of total peripheral resistance after standing in both healthy subjects and orthostatic hypotension patients. Stroke volume was not measurably altered. Among all subjects who exhibited a postural blood pressure drop >10 mmHg on the day of study, active impedance threshold device treatment consistently blunted blood pressure fall during the initial 100 seconds after standing (<0.04). Induced orthostatic symptoms were less severe with the active impedance threshold device both at onset of upright posture and during 30 seconds of standing. CONCLUSION: Enhancing impedance to inspiration may prove useful as adjunctive therapy for diminishing symptoms associated with movement to upright posture in individuals with orthostatic hypotension. PMID- 17275745 TI - Managing orthostatic hypotension: is this inspiration the answer? PMID- 17275746 TI - Regional left atrial voltage in patients with atrial fibrillation. AB - BACKGROUND: Regional differences in fibrosis, particularly related to the posterior wall and septum, may be important in atrial fibrillation (AF). Using electroanatomic mapping, voltage can be used as a measure of fibrosis. OBJECTIVES: The purpose of this study was to determine if patients with AF have disproportionately lower voltage in the septal and posterior walls of the left atrium. METHODS: Sinus rhythm left atrial electroanatomic maps were used in serial patients presenting for left atrial ablation of AF (8-mm tip). Patients undergoing left atrial mapping for focal atrial tachycardia (AT) were used as a comparison group (4-mm tip). Animal experiments were performed to assess the influence of ablation catheter tip size on voltage amplitude. RESULTS: The posterior and septal walls exhibited the lowest voltages in both groups. Compared with the anterior wall, there was a 3.78-fold greater odds of finding a low voltage point (<0.5 mV) in the septum (P <.001) and a 3.37-fold greater odds of finding a low-voltage point in the posterior wall (P <.001) in the AF patients; the proportion of low-voltage points by region were not significantly different in the AT group. In the animal model, the mean voltage obtained from an 8-mm ablation catheter was significantly higher (0.30 +/- 0.17 mV) than that obtained from the same points using a 4-mm catheter (0.22 +/- 0.17, P = .05). CONCLUSION: Regional differences in voltage are present in patients with atrial arrhythmias, with AF patients exhibiting significantly more low-voltage areas in the septum and posterior walls. PMID- 17275747 TI - Substrate mapping and the aging atrium. PMID- 17275748 TI - Left ventricular resynchronization predicted by individual performance of right and left univentricular pacing: a study on the impact of sequential biventricular pacing on ventricular dyssynchrony. AB - BACKGROUND: There is increasing evidence that improvement in left ventricular (LV) mechanical dyssynchrony is correlated with LV functional recovery in patients undergoing cardiac resynchronization therapy (CRT). Recent studies have suggested that sequential biventricular pacing may be important for further optimizing parameters of ventricular dyssynchrony. OBJECTIVE: The purpose of this study was to evaluate the acute effect of varying sequential biventricular pacing settings on echocardiographic parameters of ventricular dyssynchrony and to identify predictors of the optimal setting. METHODS: Twenty-nine patients referred for CRT were evaluated with standard echocardiography and tissue Doppler imaging before and after implantation. Indices of interventricular and intraventricular dyssynchrony were assessed for trends during simultaneous and sequential biventricular pacing. RESULTS: Twelve patients (41%) demonstrated linear trends of decreasing systolic dyssynchrony index with increasing LV preactivation. The mean additional decrease in dyssynchrony index at the optimized setting compared with simultaneous biventricular pacing was 26% (P <.04). Twenty-two patients (76%) demonstrated linear trends to decreasing interventricular dyssynchrony with increasing LV preactivation. The trends were strongly correlated with the magnitude of difference of the respective dyssynchrony measures in right ventricular only and LV only univentricular pacing. A significantly, superior capacity of LV only pacing for ventricular resynchronization was found in this subgroup of patients. CONCLUSION: In patients undergoing CRT, differences in the performance of univentricular pacing are associated with linear trends in ventricular dyssynchrony parameters in sequential biventricular pacing. Quantitative differences in LV univentricular pacing impact on the capacity of biventricular pacing to correct ventricular dyssynchrony. PMID- 17275749 TI - Clinical experience with pacemaker pulse generators and transvenous leads: an 8 year prospective multicenter study. AB - BACKGROUND: Pacemakers have improved the lives of patients worldwide. Unfortunately, the medical community has had little independent information regarding the performance of these vital medical devices. OBJECTIVES: The purpose of this study was to examine the reasons pacemaker pulse generators and transvenous leads were removed from service. We evaluated the causes and major adverse clinical events associated with device end-of-service life behavior and how they were detected and managed. METHODS: Pulse generator and lead data were entered prospectively using a web-based format. Normal battery depletion was signified by the elective replacement indicator appearing >3 years after implant. Lead failure was a device defect causing pacing, sensing, or fixation malfunction, high threshold, or abnormal impedance. Major adverse clinical events were death, angina, heart failure, syncope, and perioperative surgical complications. RESULTS: From 1998 to 2006, 2,652 pulse generator and 615 leads were removed from service. The average pulse generator was implanted for 7.3 +/- 3.1 years (range <1 day to 26 years). The majority of pulse generators (n = 2,317 [87%]) were replaced for normal battery depletion. Severe and accelerated battery depletion, manufacturers' advisories, and electronic or connector defects accounted for 13% of pulse generator removals. The proportion of pulse generators removed from service as a result of manufacturers' advisories, electronic failure, and housing defects were 4%, 2%, and 1%, respectively. Models with rate response capability had shorter battery longevities than those without rate response capability. Major adverse clinical events due to pulse generator end-of service life behavior were related to electronic and connector defects, and both normal and severe battery depletion. Median time to lead failure was 7.2 +/- 5.2 years. Insulation defects caused the majority of lead failures, and most of these leads used polyurethane materials. Lead failure was associated with a 16% incidence of major adverse clinical events. No major adverse clinical events occurred when impending lead failure was detected at routine follow-up. Lead extraction was associated with a 5.6% complication rate, including one death. CONCLUSION: Overall pulse generator performance was satisfactory. Differences in battery longevity were observed among models. In some patients, elective replacement indicators signifying normal battery depletion resulted in major adverse clinical events. Pacemaker follow-up effectively identified pulse generator end-of-service life and often detected impending lead failure, thus avoiding major adverse clinical events. Long-term studies are needed to assess chronic lead performance so that appropriate clinical management strategies, including recommendations for lead extraction, can be developed. PMID- 17275750 TI - Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3. AB - BACKGROUND: Sudden infant death syndrome (SIDS) is one of the leading causes of death during the first year of life. Long QT syndrome (LQTS)-associated mutations may be responsible for 5% to 10% of SIDS cases. We recently established CAV3 encoded caveolin-3 as a novel LQTS-associated gene with mutations producing a gain-of-function, LQT3-like molecular/cellular phenotype. OBJECTIVE: The purpose of this study was to determine the prevalence and functional properties of CAV3 mutations in SIDS. METHODS: Using polymerase chain reaction, denaturing high performance liquid chromatography, and DNA sequencing, postmortem genetic testing of CAV3 was performed on genomic DNA isolated from frozen necropsy tissue on a population-based cohort of unrelated cases of SIDS (N = 134, 57 females, average age = 2.7 months). CAV3 mutations were engineered using site-directed mutagenesis and heterologously expressed in HEK293 cell lines stably expressing the SCN5A encoded cardiac sodium channel. RESULTS: Overall, three distinct CAV3 mutations (V14L, T78M, and L79R) were identified in three of 50 black infants (6-month-old male, 2-month-old female, and 8 month-old female), whereas no mutations were detected in 83 white infants (P <.05). CAV3 mutations were more likely in decedents 6 months or older (2/12) than in infants who died before 6 months (1/124, P = .02). Voltage clamp studies showed that all three CAV3 mutations caused a significant fivefold increase in late sodium current compared with controls. CONCLUSION: This study provides the first molecular and functional evidence implicating CAV3 as a pathogenic basis of SIDS. The LQT3-like phenotype of increased late sodium current supports an arrhythmogenic mechanism for some cases of SIDS. PMID- 17275751 TI - Sudden infant death syndrome and long QT syndrome: the zealots versus the naysayers. PMID- 17275752 TI - Torsades de pointes complicating atrioventricular block: evidence for a genetic predisposition. AB - BACKGROUND: The prevalence of genetic risk factors has not been systematically evaluated in the setting of complete atriventricular (AV) block complicated by long QT syndrome (LQTS). OBJECTIVE: This study was performed to determine to what extent acquired LQTS in the context of AV block has a genetic substrate. METHODS: Among 420 recipients of pacemakers implanted over a 3-year period, we identified retrospectively 29 patients with complete AV block and a QT interval >600 ms in duration. A second study group included 22 randomly selected patients who had AV block and a QT interval <600 ms. Normal controls were 100 consecutive individuals without medical history. Genetic studies screening for HERG, KCNQ1 KCNE1, KCNE2, and SCN5A mutations were performed. RESULTS: We identified four mutations on genes encoding potassium channels in five patients with AV block and acquired LQTS. These mutations were not found among patients with AV block and a QT interval <600 ms in duration or in healthy volunteers. Functional expression of three HERG mutations (R328C, R696C, and R1047L) had a dominant negative effect on wild-type I(Kr). One KCNE2 mutation (R77W) identified in a patient treated with flecainide did not alter I(Kr). CONCLUSIONS: This study showed that complete AV block complicated by LQTS was associated with HERG mutations in 17% of cases. Further studies are needed to identify factors, genetic or environmental, which may be implicated in bradycardia-related abnormalities of ventricular repolarization. PMID- 17275753 TI - Mechanism of origin of conduction disturbances in aging human atrial bundles: experimental and model study. AB - BACKGROUND: Aging is associated with a significant increase in atrial tachyarrhythmias, especially atrial fibrillation. A macroscopic repolarization gradient created artificially by a stimulus at one site before a premature stimulus from a second site is widely considered to be part of the experimental protocol necessary for the initiation of such arrhythmias in the laboratory. How such gradients occur naturally in aging atrial tissue is unknown. OBJECTIVE: The objective of this study was to determine if the pattern of cellular connectivity in aging human atrial bundles produces a mechanism for variable early premature responses. METHODS: Extracellular and intracellular potentials were recorded after control and premature stimuli at a single site in aging human atrial bundles. We also measured cellular geometry, the distribution of connexins, and the distribution of collagenous septa. A model of the atrial bundles was constructed based on the morphological results. Action potential propagation and the sodium current were analyzed after premature stimuli in the model. RESULTS: Similar extracellular potential waveform responses occurred after early premature stimuli in the aging bundles and in the model. Variable premature conduction patterns were accounted for by the single model of aging atrial structure. A major feature of the model results was that the conduction events and the magnitude of the sodium current at multiple sites were very sensitive to small changes in the location and the timing of premature stimuli. CONCLUSION: In aging human atrial bundles stimulated from only a single site, premature stimuli induce variable arrhythmogenic conduction responses. The generation of these responses is greatly enhanced by remodeling of cellular connectivity during aging. The results provide insight into sodium current structural interactions as a general mechanism of arrhythmogenic atrial responses to premature stimuli. PMID- 17275754 TI - Aging and atrial fibrillation research: where we are and where we should go. PMID- 17275755 TI - Temperature modulation of ventricular arrhythmogenicity in a canine tissue model of Brugada syndrome. AB - BACKGROUND: Fever promotes ventricular arrhythmias in Brugada syndrome (BrS). Hypothermia can induce BrS electrocardiogram (ECG) and arrhythmia. However, the mechanisms are unclear. OBJECTIVE: We evaluated the hypothesis that pathological temperatures promoted arrhythmogenesis by modulating the spatial heterogeneity and functional dynamics of right ventricular electrophysiological activity. METHODS: We mapped action potentials (APs) on the epicardial or cut-exposed transmural surfaces and recorded transmural ECGs in 27 arterially perfused canine right ventricular preparations before and after inducing BrS at 32 degrees C, 36.5 degrees C, and 40 degrees C. RESULTS: We observed major intraepicardial dispersion of AP duration (APD) and reversal of transmural gradient of APD in association with manifestation of BrS at 36.5 degrees C. Reducing the temperature to 32 degrees C prolonged APDs and enhanced the phase 1 notch of epicardial APs, while 40 degrees C caused opposite changes. Prominent phase 2 domes of APs frequently led to spontaneous premature ventricular activations (PVAs), which conducted to surrounding regions having shorter APDs. Longer APDs at 32 degrees C and 36.5 degrees C frequently blocked reentry, although they promoted PVA, while shortened APDs at 40 degrees C facilitated reentrant ventricular tachycardia. During bradycardia (2,000 ms), the J-ST elevation in the ECG was enhanced at 32 degrees C and attenuated at 40 degrees C. Rapid pacing (500 ms) eliminated the dome of epicardial APs and enhanced J-ST elevation at each temperature. Blocking the transient outward current, I(to), with 4-aminopyridine reduced J-ST elevation and eliminated the PVA and reentry. CONCLUSIONS: In this BrS model, prolongation and increased dispersion of APDs promoted spontaneous activation during hypothermia, while APD abbreviation facilitated reentry during hyperthermia. I(to) mediated the arrhythmogenicity. PMID- 17275757 TI - The effect of lesion size and tissue remodeling on ST deviation in partial thickness ischemia. AB - BACKGROUND: Myocardial ischemia causes ST segment elevation or depression in electrocardiograms and epicardial leads. ST depression in epicardium overlying the ischemic zone indicates that the ischemia is nontransmural. However, nontransmural ischemia does not always cause ST depression. Especially in animal models, ST depression is hard to reproduce. OBJECTIVE: The purpose of this study was to determine the circumstances in which ST depression could be expected. METHODS: We studied ischemia in a large-scale computer model of the human heart. A realistic representation of the ischemia-induced changes in resting membrane potential was used, which was based on diffusion of extracellular potassium. Ischemia diameter, transmural extent, and tissue conductivity were varied. RESULTS: Our simulations confirm earlier work showing that partial-thickness ischemia, like full-thickness ischemia, typically causes ST elevation in an anisotropic model of the ventricles. However, we identified three situations in which ST depression can occur in overlying leads. The first is a reduced anisotropy ratio of the intracellular conductivity, which may result from hypertrophy and gap-junctional remodeling, circumstances that are likely to accompany ischemia. Second, an increase of the extracellular anisotropy has the same effect. Third, ST depression was found, independent of the anisotropy ratios, in very large and thin ischemic regions, resembling those that may occur in left-main or multivessel disease. CONCLUSION: Both tissue remodeling and geometric factors can explain ST depression in overlying epicardial leads. We note at the same time that ST elevation is found in most circumstances, while depression occurs as a reciprocal effect, even in partial-thickness ischemia. PMID- 17275756 TI - How can a single mutation cause such arrhythmic havoc? PMID- 17275758 TI - ST-segment elevation or TQ-segment depression? PMID- 17275761 TI - Fluctuation of atrial and ventricular lead impedances heralding subtotal separation of device header and generator in a patient with an implantable cardioverter-defibrillator. PMID- 17275760 TI - Nonenhanced magnetic resonance imaging for characterization of acute and subacute radiofrequency ablation lesions. PMID- 17275762 TI - Transvenous catheter-based microwave ablation for atrial flutter. PMID- 17275759 TI - Characterization of acute and subacute radiofrequency ablation lesions with nonenhanced magnetic resonance imaging. AB - BACKGROUND: Magnetic resonance imaging (MRI) has the potential to visualize radiofrequency (RF) ablations, which have become the preferred strategy for treatment of many arrhythmias. However, MRI patterns after RF ablation have not been well investigated. OBJECTIVE: The purpose of this study was to define the characteristic appearance and the effect of time and energy on noncontrast enhanced MRI of RF ablation. METHODS: Using a power-controlled, cooled-tip ablation system, RF ablation lesions (5-50 W for 45 seconds) were created on the right ventricular epicardium in 10 mongrel dogs. T1- and T2-weighted MR images were obtained during 12-hour follow-up and compared with gross anatomy and histopathology. RESULTS: Lesions were successfully visualized with T2- and T1 weighted images 30 minutes to 12 hours after RF ablation. T2 images were more consistent and displayed a characteristic elliptical, high-signal core (contrast to-noise-ratio [CNR] = 18.9 +/- 8.4) with a surrounding 0.5-mm low-intensity rim that on histopathology corresponded to the central tissue necrosis and the transition zone, respectively. T1 images showed a less remarked increase in signal intensity (CNR = 9.6 +/- 7.4) without a surrounding rim. Lesion size and appearance were well defined and unchanged during the 12-hour follow-up (analysis of variance). CNR was independent of applied RF energy and allowed accurate assessment of RF ablation at all time points (r = 0.87 and r = 0.83 for T2 and T1 images, respectively). Transmural lesions, interlesional gaps, and intralesional pathology could be reliably predicted in >90%. CONCLUSION: Noncontrast-enhanced MRI allows accurate assessment of RF ablation and its intralesional pathology during 12-hour follow-up. This finding confirms a possible role of MRI in guiding and evaluating RF application during electrophysiologic ablation procedures. PMID- 17275764 TI - Cardiac myocyte-nonmyocyte electrotonic coupling: implications for ventricular arrhythmogenesis. PMID- 17275763 TI - Atrioventricular junction ablation combined with either right ventricular pacing or cardiac resynchronization therapy for atrial fibrillation: the need for large scale randomized trials. AB - BACKGROUND: Nonrandomized studies suggest that atrioventricular (AV) junction ablation and pacemaker implantation may improve quality of life, ejection fraction, and exercise tolerance in patients with symptomatic drug-refractory atrial fibrillation. OBJECTIVE: The purpose of this study was to determine whether recent randomized trials support the use of AV junction ablation in combination with conventional right ventricular pacemaker therapy or cardiac resynchronization therapy (CRT) in atrial fibrillation. METHODS: Meta-analysis of randomized trials comparing AV junction ablation vs drugs or CRT vs right ventricular pacing for atrial fibrillation. RESULTS: Six randomized trials with 323 patients compared AV junction ablation vs pharmacologic therapy. The majority of these trials did not individually report a statistically significant improvement in survival, stroke, hospitalization, functional class, atrial fibrillation-associated symptoms, left ventricular ejection fraction, exercise capacity, healthcare costs, or quality of life. Overall, all-cause mortality was 3.5% for AV junction ablation patients and 3.3% for controls (relative risk 1.18, 99% confidence interval 0.26-5.22). Three randomized trials with 347 patients compared CRT vs right ventricular pacing in atrial fibrillation. These trials did not individually report a statistically significant improvement in survival, stroke, hospitalization, exercise capacity, or healthcare costs. CRT was associated with a statistically significant improvement in ejection fraction in two of the three trials. Overall, CRT was associated with a trend toward reduced all-cause mortality relative to controls (relative risk 0.51, 99% confidence interval 0.22-1.16). All-cause mortality was 7.1% for CRT patients and 14% for controls. CONCLUSION: Limited randomized trial data have been published regarding AV junction ablation in combination with conventional pacemaker therapy or CRT for atrial fibrillation. Large-scale randomized trials are needed to assess the efficacy of these therapies. PMID- 17275766 TI - What is the rhythm: ventricular or supraventricular? PMID- 17275765 TI - Reentry around the heart. PMID- 17275767 TI - How to use intracardiac echocardiography for atrial fibrillation ablation procedures. PMID- 17275768 TI - Left-sided implantation of biventricular implantable cardioverter-defibrillators in dextrocardia. PMID- 17275769 TI - Left-sided implantation of a biventricular implantable cardioverter-defibrillator in dextrocardia. PMID- 17275770 TI - Clinical considerations for Heart Rhythm allied professionals: understanding heart failure in congenital heart disease patients. PMID- 17275772 TI - Elevated defibrillation thresholds (DFTs) among recipients of a biventricular implantable cardioverter-defibrillator (ICD). PMID- 17275774 TI - Age-related differences in street-crossing decisions: the effects of vehicle speed and time constraints on gap selection in an estimation task. AB - Two experiments were conducted to study how age affects street-crossing decisions in an estimation task, with particular emphasis on how oncoming vehicle speed and a time constraint influence the time gap deemed acceptable for crossing. Experiment 1 showed that when there was a time constraint, all age groups selected a shorter time gap for the higher speed. This was associated with a large number of missed opportunities for the low speed and many unsafe decisions for the high speed. In the second experiment, which had no time constraint, young pedestrians operated in a constant-time mode regardless of speed, whereas older pedestrians accepted shorter and shorter time gaps as speed increased. The results seem to indicate that the effect of speed is due to a mixed operating mode of participants, whose decisions may be based on either time or vehicle distance, depending on the task requirements and on the participant's own ability to meet those requirements. PMID- 17275773 TI - The impact of outlet densities on alcohol-related crashes: a spatial panel approach. AB - BACKGROUND: A number of studies using cross-sectional data have demonstrated that the availability of alcohol, measured by the number and types of alcohol outlets, is directly related to numerous measures associated with drinking and driving. The current study contributes the first observation of relationships over time between alcohol outlet densities on one hand and both automobile crashes and related injuries on the other hand. METHOD: The study examined longitudinal data from 581 consistently defined zip code areas represented in the California Index Locations Database, a geographic information system that coordinates population and ecological data with spatial attributes for areas across the state. Six years of data were collected on features of local populations (e.g., demographics, household size) and places (e.g., retail markets) thought to be related to two measures of automobile crashes (hospital discharges related to car crash injuries geocoded to the zip code of patient residence, and police reports associated with car crashes geocoded to the zip code of crash location). Both crash measures were positively associated with two outlet types: bars, and off-premise outlets. Additionally, restaurants appear to provide a protective effect relative to the residence-based measure. Crash rates were also related to changes in population and place characteristics using random effects models with controls for spatial autocorrelation (nxt=3486 observations). Changes in population and place characteristics of adjacent (spatially lagged) areas were also considered. RESULTS: Over time, both local and lagged population and place characteristics were related to automobile crash-related measures. CONCLUSION: Controlling for cross-sectional differences between zip code areas, changes in numbers of licensed alcohol retail establishments, especially bars and off-premise outlets, affect rates of car crashes and related injuries. PMID- 17275775 TI - In-gel fluorescence probing of RNA-RNA interactions. PMID- 17275776 TI - Effects of backrest design on biomechanics and comfort during seated work. AB - The purpose of this study was to examine the effects of backrest configuration on seatpan and backrest pressure, spinal posture, and comfort. Thirty volunteers (15 male, 15 female) typed a standardized text passage while seated at a computer workstation in five backrest configurations: chair only, chair with a supplementary backrest, and with each of three lumbar pad thicknesses. Pressure, lumbar and cervical angles were collected during 15-min trials. Subjective data were collected during each trial and at the end of the entire protocol. The addition of a supplementary backrest to a standard chair reduced peak and average pressure on the back by 35% and 20%, respectively (P<0.02). Lumbar lordosis was observed only when lumbar pads were used, being greatest with the large pad. Participants preferred backrest configurations that had lower pressure on the back and less lordotic lumbar posture (backrest only or 3 cm lumbar pad), regardless of anthropometrics. Comfort was rated highest in conditions that would not necessarily be considered biomechanically ideal. Further delineation between specific comfort and objective seating variables is required to effectively reduce and prevent low back pain. PMID- 17275777 TI - Chewing in patients with severe neurological impairment. AB - OBJECTIVE AND DESIGN: As degenerative disease, infarction and hemorrhage in the CNS may compromise chewing, the aim was to classify and analyse such chewing disturbances. The case series included clinical and electromyographic recordings from 10 patients (ages 12-78 years) with neurological disorders. RESULTS: Classifications were involuntary munching (two women with dystonia which was abolished during mastication), ceased chewing function (three men with impaired volitional motor control and spasticity from locked-in syndrome, restricted chewing range (two men and one woman with reduced jaw opening due to paradoxical activity after brainstem lesions), and distorted chewing pattern (two men with dystonia resulting in blockings during chewing). CONCLUSION: The effect of the neurological impairment illustrated the complex control of mastication and the interaction between central and peripheral mechanisms, and the variation of the chewing disturbances was surprisingly great, even with similar diagnosis. PMID- 17275778 TI - Egg yolk-derived immunoglobulin (IgY) against Porphyromonas gingivalis 40-kDa outer membrane protein inhibits coaggregation activity. AB - The anaerobic bacterium Porphyromonas gingivalis, a major pathogen in periodontitis, aggregates with a number of oral bacteria to form dental plaque, which is important for its colonization. We previously cloned the gene coding the 40-kDa outer membrane protein (OMP) of P. gingivalis 381 and produced large amounts of the recombinant (r) protein. Affinity-purified rabbit antiserum against r40-kDa OMP effectively inhibited the coaggregation activity of P. gingivalis to oral bacteria, thus 40-kDa OMP was thought to be an important coaggregation factor of P. gingivalis. Further, since it is conserved among many P. gingivalis strains, this coaggregation factor may be an effective target for passive immunotherapy against P. gingivalis infection. Recently, passive immunization approaches using a specific antibody produced from hen egg yolk (IgY) have been developed for oral infectious diseases, and shown to be convenient and economic. In the present study, we immunized hens intramuscularly with r40-kDa OMP and obtained highly purified IgY from the egg yolks. The purified IgY specifically recognized r40-kDa OMP and also reacted with a functional coaggregation-associated domain peptide of 40-kDa OMP. Our results demonstrated that a ratio of purified IgY as low as 2.5 microg/150 microl significantly inhibited the coaggregation of P. gingivalis with Streptococcus gordonii, which was verified by a visual coaggregation assay and radioactivity based quantitative micro-coaggregation assay. We concluded anti-r40-kDa OMP IgY may be useful for passive immunization against periodontal diseases caused by P. gingivalis infection. PMID- 17275779 TI - Atomic force microscopy study of the antimicrobial action of Sushi peptides on Gram negative bacteria. AB - The antibacterial effect of the endotoxin-binding Sushi peptides against Gram negative bacteria (GNB) is investigated in this study. Similar characteristics observed for Atomic force microscopy (AFM) images of peptide-treated Escherichia coli and Pseudomonas aeruginosa suggest that the Sushi peptides (S3) evoke comparable mechanism of action against different strains of GNB. The results also indicate that the Sushi peptides appear to act in three stages: damage of the bacterial outer membrane, permeabilization of the inner membrane and disintegration of both membranes. The AFM approach has provided vivid and detailed close-up images of the GNB undergoing various stages of antimicrobial peptide actions at the nanometer scale. The AFM results support our hypothesis that the S3 peptide perturbs the GNB membrane via the "carpet-model" and thus, provide important insights into their antimicrobial mechanisms. PMID- 17275780 TI - Profilin binding to sub-micellar concentrations of phosphatidylinositol (4,5) bisphosphate and phosphatidylinositol (3,4,5) trisphosphate. AB - Profilin is a small (12-15 kDa) actin binding protein which promotes filament turnover. Profilin is also involved in the signaling pathway linking receptors in the cell membrane to the microfilament system within the cell. Profilin is thought to play critical roles in this signaling pathway through its interaction with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] (P.J. Lu, W.R. Shieh, S.G. Rhee, H.L. Yin, C.S. Chen, Lipid products of phosphoinositide 3-kinase bind human profilin with high affinity, Biochemistry 35 (1996) 14027-14034). To date, profilin's interaction with polyphosphoinositides (PPI) has only been studied in micelles or small vesicles. Profilin binds with high affinity to small clusters of PI(4,5)P(2) molecules. In this work, we investigated the interactions of profilin with sub-micellar concentrations of PI(4,5)P(2) and PI(3,4,5)P(3). Fluorescence anisotropy was used to determine the relevant dissociation constants for binding of sub-micellar concentrations of fluorescently labeled PPI lipids to profilin and we show that these are significantly different from those determined for profilin interaction with micelles or small vesicles. We also show that profilin binds more tightly to sub-micellar concentrations of PI(3,4,5)P(3) (K(D)=720 microM) than to sub-micellar concentrations of PI(4,5)P(2) (K(D)=985 microM). Despite the low affinity for sub-micellar concentration of PI(4,5)P(2), profilin was shown to bind to giant unilamellar vesicles in presence of 0.5% mole fraction of PI(4,5)P(2) The implications of these findings are discussed. PMID- 17275781 TI - A randomised controlled trial of cognitive-behaviour therapy for clinical perfectionism: a preliminary study. AB - Perfectionism can be a problem in its own right and it can impede the progress of treatment of Axis I disorders. This study reports on a preliminary randomised controlled trial of cognitive-behaviour therapy (CBT) for "clinical perfectionism". Twenty participants were randomly assigned to either immediate treatment (IT) (n=10) or a wait list (NL) (n=10). Treatment consisted of ten sessions of CBT over eight weeks. Two participants did not complete the follow-up assessments (10%). Fifteen of the original 20 participants (75%) were clinically significantly improved after treatment and the effect size was large (1.8). Treatment gains were maintained at 8-week and 16-week follow-up. PMID- 17275782 TI - Prediction of interaction mode between a typical ACE inhibitor and MMP-9 active site. AB - To characterize the inhibitory specificity of angiotensin converting enzyme (ACE) inhibitors for matrix metalloproteinase 9 (MMP-9) activity, molecular modeling of these complex was performed referring the recent X-ray structure analyses using lisinopril as an ACE inhibitor. Two interaction modes differing in the orientation of the inhibitor on the active site were identified. Lisinopril was effectively stabilized by specific hydrogen bonds and hydrophobic interactions in the active site of MMP-9, and its hydrophobic group appeared to interact preferentially with the S1 site compared with the S1' site. These findings showed that ACE inhibitors could become important seeds for cardiovascular protection and the development of MMP inhibitors. PMID- 17275783 TI - Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part I. fusion [corrected] inhibition. AB - We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with I573, G572, and L568 on the gp41 N terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion active core. To test and confirm modeling predications, we examined the effect of Ole and HT on HIV-1 fusion complex formation using native polyacrylamide gel electrophoresis and circular dichroism spectroscopy. Ole and HT exhibit dose dependent inhibition on HIV-1 fusion core formation with EC(50)s of 66-58nM, with no detectable toxicity. Our findings on effects of HIV-1 integrase are reported in the subsequent article. PMID- 17275784 TI - Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice. AB - Vascular and cellular invasion into the cartilage is a critical step in the fracture healing. Matrix metalloproteinase-13 (MMP-13) is a member of the zinc dependent endopeptidase family and plays an important role in remodeling of extracellular matrix. Therefore we investigated the possible involvement of MMP 13 in a murine model of stabilized bone fracture healing. Repair of the fracture in MMP-13 deficient (MMP-13(-/-)) mice was significantly delayed and characterized by a retarded cartilage resorption in the fracture callus. Immunohistochemistry indicated severe defects in vascular penetration and chondroclast recruitment to the fracture callus in MMP-13(-/-) mice. Consistent with the observations, the chondrocyte pellets cultured from the MMP13(-/-) mice exhibited diminished angiogenic activities when the pellets were co-cultured with endothelial cells. These results suggest that MMP-13 is crucial to the process of angiogenesis during healing of fracture, especially in the cartilage resorption process. PMID- 17275785 TI - Regulation of ERK5 by insulin and angiotensin-II in vascular smooth muscle cells. AB - ERK5 is involved in proliferation of vascular smooth muscle cells (VSMC). The proliferative actions of insulin and angiotensin-II (A-II) in VSMC are mediated in part by ERK1/2. We hypothesized that insulin and A-II also regulate ERK5 activity in VSMC. Acute treatment (<60min) with insulin or A-II increased phosphorylation of ERK1/2 at 15min and ERK5 at 5min. Chronic treatment (< or = 8h) with insulin increased ERK1/2 phosphorylation by 4h and ERK5 by 8h. A-II stimulated phosphorylation of ERK1/2 by 8h and ERK5 by 4h. The EC(50) for insulin treatment effecting ERK1/2 and ERK5 phosphorylation was 1.5 and 0.1nM, whereas the EC(50) for A-II was 2nM, each. Insulin plus A-II induced an additive effect only on ERK5 phosphorylation. Inhibition of insulin- and A-II-stimulated phosphorylation of ERK5 and ERK1/2 by PD98059 and Wortmannin exhibited differential and time-dependent effects. Taken together, these data indicate that insulin and A-II regulate the activity of ERK5, but different from that seen for ERK1/2. PMID- 17275786 TI - Enrichment of G4 DNA motif in transcriptional regulatory region of chicken genome. AB - G-quadruplex or G4 DNA is a stable, four-stranded DNA structure formed from guanine-rich regions. Based on the hypothesis that G4 DNA participated in the regulation of transcription, we analyzed G4 DNA in 5kb 5' flanking regions of 2892 chicken RefSeq genes with annotated transcription start sites (TSS). In total, 4769 distinct putative G4 DNA motifs (G4M) were identified in 1880 (65%) genes. The pattern of distribution of the G4M showed a gradient along the 5' flanking regions; from -5 to -4kb, to -1kb to the TSS, the frequency (number of G4M per kilobase) increased significantly from 0.192 to 0.768, and 62.56% of the G4M in the 1kb upstream regions were located in the region -400 to the TSS, where a core promoter is always present. Thus, 38.24% of the analyzed genes contained at least one G4M in the 400bp upstream region. Our findings support the hypothesis that G4M are involved in gene transcription. PMID- 17275787 TI - MERRF syndrome without ragged-red fibers: the need for molecular diagnosis. AB - We report a patient with myoclonic epilepsy who underwent muscle biopsy for suspected mitochondrial disease (myoclonic epilepsy with ragged-red fibers, MERRF). In spite of normal histochemical studies and of the absence of a severe COX deficiency, the molecular analysis showed the common MERRF mutation (A8344G) in the tRNA(Lys) gene on mitochondrial DNA. The case serves to illustrate the importance of pursuing the proposed mitochondrial genetic abnormality, even in patients with normal biopsy findings. PMID- 17275788 TI - Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation. AB - Signaling by Toll-like receptors (TLRs) is central to evoking innate immunity, wherein each TLR is activated by distinct pathogen-derived agonists. It has been shown previously that TLR signaling occurs in synergy when certain TLR agonist combinations simultaneously activate immune cells. This synergism may constitute a mechanism critical to ensuring the effective activation of the immune system by multiple TLR activating molecules associated with a given pathogen; however, its underlying mechanism(s) remain unclarified. Here, we provide evidence that TLRs utilizing the MyD88 adaptor selectively cooperate with those utilizing the TRIF adaptor for synergistic induction of a set of target genes, and that this synergism is abrogated in cells lacking either MyD88 or TRIF. Moreover, we also provide evidence that this TLR synergy is mediated, at least in part, by activation of the transcription factor interferon regulatory factor 5 (IRF5). Thus, our findings offer a mechanistic insight into TLR synergy, revealing the hitherto unknown cross talk between the MyD88 and TRIF pathways for a robust TLR mediated activation of the immune system. PMID- 17275789 TI - PPARdelta, but not PPARalpha, activates PGC-1alpha gene transcription in muscle. AB - PGC-1alpha induces mitochondrial biogenesis in muscle and its activity has been related to insulin sensitization. Here, we report that fibrates induce PGC-1alpha gene expression in muscle both in vivo and in vitro. However, only activation via PPARdelta but not PPARalpha underlies this effect. PPARdelta induces PGC-1alpha gene transcription through a PPAR-response element in the PGC-1alpha promoter. Moreover, PGC-1alpha coactivates the PPARdelta-responsiveness of its own gene. A further positive autoregulatory loop of control relies on the induction of PPARdelta expression by PGC-1alpha. These data point to a distinct value of PPARdelta rather than PPARalpha agonists in the improvement of oxidative metabolism in muscle. PMID- 17275790 TI - Modified sympathetic regulation in N-type calcium channel null-mouse. AB - To elucidate the physiological importance of neuronal (N)-type calcium channels in sympathetic controls, we analyzed N-type channel-deficient (NKO) mice. Immunoprecipitation analysis revealed increased interaction between beta3 (a major accessory subunit of N-type channels) and R-type channel-forming CaV2.3 in NKO mice. R-R intervals in NKO ECG recordings were elongated and fluctuating, suggesting disturbed sympathetic tonus. N-type channel inhibitors elongated the R R interval in control mice, whereas R-type channel blocking with SNX-482 significantly affected NKO but not control mice, indicating a compensatory role for R-type channels. Echocardiography and Langendorff heart analysis confirmed a major role for R-type channels in NKO mice. Combined, our biochemical and physiological analyses strongly suggest that the remaining sympathetic tonus in NKO mice is dependent on R-type calcium channels. PMID- 17275791 TI - Voluntary ethanol drinking in mice and ethanol concentrations in the nucleus accumbens. AB - The present study determined ethanol concentrations in the nucleus accumbens (NAcc) of C57BL/6J (B6) mice voluntarily drinking ethanol using an established limited access paradigm. Lickometer circuits were employed to monitor the temporal pattern of consummatory behavior, and serial samples were collected from the NAcc using in vivo microdialysis techniques. Ethanol in the dialysate was measured by gas chromatography with flame ionization detection. During dialysis, mice preferentially consumed sufficient amounts of sweetened ethanol ( approximately 3 g/kg ethanol) to produce low millimolar levels of ethanol in dialysates from the NAcc; water intake was negligible. Overall, there was a positive relationship between total amount of ethanol consumed during the 2 h drinking session and cumulative (as well as peak) ethanol levels in NAcc. Additionally, and the total number of licking responses was positively correlated with the total amount of ethanol consumed. Moreover, the change in NAcc ethanol levels was temporally linked to the pattern of ethanol drinking, with periods of high licking responses on the ethanol tube preceding peak brain ethanol levels. The results indicate that the voluntary consumption of ethanol by B6 mice in a limited access time frame elevates ethanol concentration in NAcc dialysates in a manner consistent with the pattern of ethanol consumption. PMID- 17275792 TI - The effect of task-relevance on primary somatosensory cortex during continuous sensory-guided movement in the presence of bimodal competition. AB - Recent perceptual neuroimaging studies have shown that intermodal selective attention extracts relevant information from one modality at the expense of another at the level of unimodal sensory cortex. The present paper sought 1) to determine the effects of intermodal selective attention on primary somatosensory cortex (S1) during continuous sensorimotor transformations, 2) to investigate the interactions of spatial relationship between the target and distracter modalities on S1 and 3) to identify any potential modulators during continuous sensorimotor transformations. Functional MRI was acquired while participants (n=10) received simultaneous vibrotactile and visuospatial stimulation. In each condition, participants tracked either vibrotactile stimulation (25 Hz), applied to the right index finger with variable intensity, or a visuospatial stimulus, a centrally presented dial where the spatial position of a needle randomly moved, by applying graded force to a force sensing resistor. The distracter modality either originated from a location that was spatially related or distinct to the target that guided movement. Vibrotactile tracking resulted in decreased S1 activation relative to when it was task-irrelevant. Neither S1 activity nor tracking performance was influenced by spatial relationship. In addition the superior parietal lobe/precuneus (BA 7), inferior parietal lobe (BA 40), precentral gyrus (BA 6) and secondary visual areas (BA 18 and 19) may modulate the extraction of task-relevant information while the insula (BA 13) may do so during cases of spatial conflict. We conclude that modulation of S1 is important to the proper execution of sensory-guided movements and that sensorimotor requirements determine the mechanisms of intermodal selective attention. PMID- 17275793 TI - Long-lasting reactive changes observed in microglia in the striatal and substantia nigral of mice after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. AB - Parkinson's disease (PD) is an age-related movement disorder that progresses over a period of 10 to 20 years. The existence of microglia in a long-lasting activated state, expressing MHC II, has been thought to play an important role in the progression of PD. PD mouse models, induced by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), exhibit only transient PD-like movement dysfunction in contrast to MPTP-intoxicated monkeys which show progressive and permanent movement dysfunction. To understand the reasons why the progression does not occur in MPTP-treated mice, we used immunohistochemical analyses to study whether activated microglia in the striatum and/or substantia nigra persist long after MPTP treatment. Microglial changes in the striatum and substantia nigra of mice at 2 days and 6 months after MPTP treatment (four intraperitoneal injections of 20 mg/kg MPTP at two hour intervals) were examined. C57BL/6 mice (which are highly sensitive to MPTP) displayed transient movement dysfunction and highly activated microglia were observed at day two. In contrast, BALB/c mice (which are less sensitive to MPTP) exhibited no movement dysfunction and only slightly activated microglia were observed at day two. After 6 months, the microglia in the striatum and substantia nigra pars compacta of the treated C57BL/6 mice were still more hypertrophic compared with the control, although less hypertrophic than those observed at day two. In the treated BALB/c mice, the microglia were also hypertrophic compared with the control after 6 months. MHC II-positive microglia were undetectable at any time after MPTP treatment in both mice. These data show that MPTP administration results in the existence of persistent activated microglia that are not MHC II-positive, and is independent of the MPTP sensitivity of the mouse strain. These results suggest that long lasting MHC II positive microglia might be required for PD progression. In MPTP-intoxicated mice, the absence of MHC II-positive microglia might explain why there is no progression of PD-like dysfunctional symptoms. PMID- 17275794 TI - Unilateral vestibular deafferentation-induced changes in calcium signaling related molecules in the rat vestibular nuclear complex. AB - Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage gated Ca(2+) channels (VGCC) and intracellular Ca(2+) signaling. Indeed, our previous microarray analysis showed an up-regulation of some calcium signaling related genes such as the alpha2 subunit of L-type calcium channels, calcineurin, and plasma membrane Ca(2+) ATPase 1 (PMCA1) in the ipsilateral vestibular nuclear complex (VNC) following unilateral vestibular deafferentation (UVD). To further elucidate the role of calcium signaling-related molecules in vestibular compensation, we used a quantitative real-time polymerase chain reaction (PCR) method to confirm the microarray results and investigated changes in expression of these molecules at various stages of compensation (6 h to 2 weeks after UVD). We also investigated the changes in gene expression during Bechterew's phenomenon and the effects of a calcineurin inhibitor on vestibular compensation. Real-time PCR showed that genes for the alpha2 subunit of VGCC, PMCA2, and calcineurin were transiently up-regulated 6 h after UVD in ipsilateral VNC. A subsequent UVD, which induced Bechterew's phenomenon, reproduced a complete mirror image of the changes in gene expressions of PMCA2 and calcineurin seen in the initial UVD, while the alpha2 subunit of VGCC gene had a trend to increase in VNC ipsilateral to the second lesion. Pre-treatment by FK506, a calcineurin inhibitor, decelerated the vestibular compensation in a dose-dependent manner. Although it is still uncertain whether these changes in gene expression are causally related to the molecular mechanisms of vestibular compensation, this observation suggests that after increasing the Ca(2+) influx into the ipsilateral VNC neurons via up regulated VGCC, calcineurin may be involved in their synaptic plasticity. Conversely, an up-regulation of PMCA2, a brain-specific Ca(2+) pump, would increase an efflux of Ca(2+) from those neurons and perhaps prevent cell damage following UVD. PMID- 17275795 TI - Inhibitory effect of pinealectomy on the development of cerebellar granule cells in the chick: a stereological study. AB - Melatonin has some effects upon morphological features of various structures in small animals and human being. However, there has been no investigation concerning its physiological role on development of cerebellar granule cells. In this study, the changes induced by pinealectomy procedure on cerebellar development and their granule cell numbers in the chick were investigated using quantitative stereological methods. A total of 15 Hybro Broiler newly hatched chicks were randomly divided into three equal groups: pinealectomy group (n=5) and non-pinealectomized control group (n=5) and sham-operated group (n=5). Pinealectomy procedure and sham operation were done in 3-day-old chicks and all animals were sacrificed for histopathological evaluation and subsequent stereological analysis in the 8th week. Here, it was observed that pinealectomy significantly reduces the granular cell number in cerebellar cortex of the chicks (P<0.001). The present study is the first stereological study to evaluate the histomorphological effects of pinealectomy on the cerebellar granule cells of the chick. We suggest that the granule cell loss in the cerebellar cortex is due to developmental retardation in early postnatal period, although its exact mechanism is not clear. Based on our findings, we intimate that pineal gland/melatonin might play an important role in the development of cerebellar granule cells in the chick. PMID- 17275796 TI - Cortical contusion induces trans-hemispheric reorganization of blood flow maps. AB - Cerebral blood flow (CBF), a surrogate of neural activity in the identification of brain regions involved in specific functions, has been used in this report to trace the compensatory enhancement of activity in non-traumatized areas of the brain following a focal lesion. We have previously shown activation of CBF in the cortex contralateral to a focal contusion, 24 h after the event. The present report extends the characterization of this trans-hemispheric cortical blood flow activation by studying its time course and regional distribution from 4 days to 4 weeks post-trauma. Adult male Sprague-Dawley rats received a cortical impact through a 6.3 mm craniotomy under halothane anesthesia. CBF was measured with the quantitative autoradiographic (14)C-Iodoantipyrine technique, in conscious animals, 4 days, 2 weeks and 4 weeks post-trauma. CBF was severely decreased at the site of impact where necrosis developed later, and it remained depressed in the surrounding areas throughout the observation period. Trans-hemispheric CBF enhancement was maximal at 4 days and it returned to control levels 28 days post trauma. This phenomenon was present in all cortical regions symmetrical to the impact zone, but also in auditory, visual, entorhinal and insular cortex. These results suggest that the participation of the contralateral cortex in the recovery from unilateral brain trauma is not limited to the regions homologous to those that received the impact. The time course of CBF changes was found to be consistent with the recovery of motor function in this model. PMID- 17275797 TI - GABAergic projection neurons in the basal ganglia of the green tree frog (Hyla cinerea). AB - The basal ganglia of tetrapods have been considered to be a conservative system sharing a common pattern with respect to connectivity and transmitters. One important transmitter found in mammalian basal ganglia is gamma-aminobutyric acid (GABA) which is used by nearly all striatal and pallidal projection neurons. In order to investigate whether GABAergic projection neurons exist in the basal ganglia of anurans as well, we combined tracer applications in the diencephalic portion of the lateral forebrain bundle with GABA immunohistochemistry in an isolated brain preparation of the green tree frog Hyla cinerea. Additionally, double-labeling studies using antibodies against GABA, GAD 65, and GAD 67 helped to clarify which neurons could be regarded as GABAergic. On average 7.29-7.40% of striatal and 3.29-3.98% of pallidal projection neurons were strongly GABA immunoreactive; lightly labeled neurons were disregarded. We conclude that GABAergic projection neurons are present in the striatum and dorsal pallidum of H. cinerea, but their numbers are much lower compared to the same regions in mammals. PMID- 17275798 TI - Increases in the phosphorylated form of caveolin-1 in the spinal cord of rats with clip compression injury. AB - The phosphorylation of caveolin-1, a lipid raft protein, alters cell shape, which is an important finding in the activation and migration of inflammatory cells. We studied the level of the phosphorylated form of caveolin-1 (p-caveolin-1) in the spinal cord of rats with a clip compression injury to determine whether the phosphorylation of caveolin-1 is involved in the pathogenesis of spinal cord injury. Spinal cords, sampled on days 0, 1, 4, 7, and 14 post-injury, were analyzed by Western blot and immunohistochemistry. Western blot analysis showed that the level of p-caveolin-1 significantly increased in the spinal cord at day 4 post-injury compared to the sham-operated control (p<0.05), and its increased level remained in the elevated condition until day 14 post-injury. Immunohistochemistry showed that p-caveolin-1 was mainly localized in the macrophages/activated microglia in the injured spinal cords, even though caveolin 1 was immunodetected in neurons and reactive astrocytes as well as in inflammatory macrophages. Considering these findings, we postulated that the increased level of p-caveolin-1 is involved in intracellular signaling in affected cells, particularly macrophages/activated microglia, in the course of rat spinal cord injury. PMID- 17275799 TI - Arachidonic and docosahexaenoic acids reduce the growth of A549 human lung-tumor cells increasing lipid peroxidation and PPARs. AB - Polyunsaturated fatty acids (PUFAs) play an important role in both induction and prevention of carcinogenic process. It is well known that several types of neoplastic cells show decreased total PUFA content, contributing to their resistance to chemotherapy and lipid peroxidation. In the light of this, human lung cancer A549 cells, with low PUFA content, were exposed to arachidonic or docosahexaenoic acid to investigate the effect of n-6 and n-3 PUFAs on growth and elucidate underlying mechanisms. The bulk of the results showed that both n-6 PUFAs and n-3 PUFAs decrease human lung-tumor cell growth in a concentration dependent manner, inducing cell death mainly evident at 100microM concentration. The mechanism underlying the antiproliferative effect of n-6 and n-3 PUFAs appeared to be the same, involving changes in fatty acid composition of biomembranes, production of cytostatic aldehydes derived from lipid peroxidation and able to affect DNA-binding activity of AP-1, and induction of PPAR. From these results it may be hypothesized that n-6 PUFAs, like n-3 PUFAs, are able to inhibit tumor growth. PMID- 17275800 TI - Traces of copper ions deplete glutathione in human hepatoma cell cultures with low cysteine content. AB - BACKGROUND: Cell death induced by intracellular glutathione depletion has been reported to be dependent on the presence of trace amounts of extracellular copper ions. Since little is known about the relationship between glutathione depletion and copper homeostasis, we have in the present study further investigated the role of low amounts of copper ions in glutathione depletion. METHODS: Glutathione turnover was investigated in HeLa and hepatoma cell cultures with normal and low cysteine content in the presence of copper ions (1 and 10micromol/L) and two other glutathione-stimulating agents (lipoic acid and mercury ions). RESULTS: Copper ions (10micromol/L) caused relatively small increases in total amount of glutathione (the sum of the intracellular and the extracellular amount of glutathione) in HeLa and hepatoma cell cultures with normal cysteine levels (420nmol/mL) compared to control cell cultures, whereas lipoic acid and mercury ions strongly increased total glutathione in both types of cell cultures. Lower amount of total glutathione was observed in cell cultures with a lower cysteine levels (84nmol/mL), which is similar to that in human plasma. A strongly decreased total amount of glutathione in the presence of copper ions was observed in hepatoma cell cultures with lower cysteine levels, whereas the other agents showed effects similar to those described for cell cultures with normal cysteine levels. CONCLUSION: Glutathione synthesis in hepatoma cell cultures is probably more sensitive to a low cysteine level than HeLa cell cultures, and the presence of copper ions further decreases the availability of cysteine probably by increasing the disulfide binding to cysteine residues in extracellular proteins, which causes a further decrease of total glutathione. PMID- 17275801 TI - Bilingualism aids conflict resolution: evidence from the ANT task. AB - The need of bilinguals to continuously control two languages during speech production may exert general effects on their attentional networks. To explore this issue we compared the performance of bilinguals and monolinguals in the attentional network task (ANT) developed by Fan et al. [Fan, J., McCandliss, B.D. Sommer, T., Raz, A., Posner, M.I. (2002). Testing the efficiency and independence of attentional networks. Journal of Cognitive Neuroscience, 14, 340-347]. This task is supposed to tap into three different attentional networks: alerting, orienting and executive control. The results revealed that bilingual participants were not only faster in performing the task, but also more efficient in the alerting and executive control networks. In particular, bilinguals were aided more by the presentation of an alerting cue, and were also better at resolving conflicting information. Furthermore, bilinguals experienced a reduced switching cost between the different type of trials compared to monolinguals. These results show that bilingualism exerts an influence in the attainment of efficient attentional mechanisms by young adults that are supposed to be at the peak of their attentional capabilities. PMID- 17275802 TI - A synesthetic walk on the mental number line: the size effect. AB - Are small and large numbers represented similarly or differently on the mental number line? The size effect was used to argue that numbers are represented differently. However, recently it has been argued that the size effect is due to the comparison task and is not derived from the mental number line per se. Namely, it is due to the way that the mental number line is mapped onto the task relevant output component. Here synesthesia was used to disentangle these two alternatives. In two naming experiments a digit-color synesthete showed that the congruity effect was modulated by number size. These results support the existence of a mental number line with a vaguer numerical representation as numbers increase in size. In addition, the results show that in digit-color synesthesia, colors can evoke numerical representation automatically. PMID- 17275803 TI - The arts and sciences of Lawrence Stark. PMID- 17275805 TI - Beta catenin-independent activation of MyoD in presomitic mesoderm requires PKC and depends on Pax3 transcriptional activity. AB - Early activation of myogenesis in the somite depends on signals from surrounding tissues. Canonical beta-catenin dependent Wnt signalling preferentially activates Myf5. We now show, in explant experiments with presomitic mesoderm, that the expression of another myogenic determination factor, MyoD, depends on non canonical Wnt signalling, probably emanating from the dorsal ectoderm. Inhibitors of PKC block MyoD expression, indicating that the intracellular Wnt pathway depends on this kinase. In the absence of Myf5 and Mrf4, this activation is only minorily affected and we identify Pax3 as the transcriptional mediator responsible for MyoD expression. When embryos expressing a constitutively active form of Pax3, PAX3-FKHR, are used for these studies in the presence of PKC inhibitors, MyoD expression is not affected, suggesting that Wnt signalling acts on the transcriptional activity of Pax3. PMID- 17275804 TI - FGF-mediated induction of ciliary body tissue in the chick eye. AB - Upon morphogenesis, the simple neuroepithelium of the optic vesicle gives rise to four basic tissues in the vertebrate optic cup: pigmented epithelium, sensory neural retina, secretory ciliary body and muscular iris. Pigmented epithelium and neural retina are established through interactions with specific environments and signals: periocular mesenchyme/BMP specifies pigmented epithelium and surface ectoderm/FGF specifies neural retina. The anterior portions (iris and ciliary body) are specified through interactions with lens although the molecular mechanisms of induction have not been deciphered. As lens is a source of FGF, we examined whether this factor was involved in inducing ciliary body. We forced the pigmented epithelium of the embryonic chick eye to express FGF4. Infected cells and their immediate neighbors were transformed into neural retina. At a distance from the FGF signal, the tissue transitioned back into pigmented epithelium. Ciliary body tissue was found in the transitioning zone. The ectopic ciliary body was never in contact with the lens tissue. In order to assess the contribution of the lens on the specification of normal ciliary body, we created optic cups in which the lens had been removed while still pre-lens ectoderm. Ciliary body tissue was identified in the anterior portion of lens-less optic cups. We propose that the ciliary body may be specified at optic vesicle stages, at the same developmental stage when the neural retina and pigmented epithelium are specified and we present a model as to how this could be accomplished through overlapping BMP and FGF signals. PMID- 17275806 TI - Vasopressin promotes cardiomyocyte hypertrophy via the vasopressin V1A receptor in neonatal mice. AB - [Arg8]-vasopressin (AVP) is an essential hormone for maintaining osmotic homeostasis and is known to be a potent vasoconstrictor that regulates the cardiovascular system. In the present study, cardiomyocytes were isolated from neonatal mice and used to investigate the effects of AVP on cardiac hypertrophy. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that vasopressin V1A receptor mRNA, but not V1B or V2 receptor mRNA, was expressed in primary cultured neonatal mouse cardiomyocytes. By exposing the cultured neonatal cardiomyocytes to AVP for 24 h, cell surface areas were significantly increased, suggesting that AVP could induce cardiomyocyte growth. We then investigated the expression level of the atrial natriuretic peptide (ANP), which is a marker of cardiac hypertrophy. Stimulation with AVP increased the expression of cardiomyocyte ANP mRNA in a dose- and time-dependent manner. Immunocytochemical studies showed that stimulation with AVP significantly increased the expression of the ANP protein as well. Furthermore, AVP administration activated extracellular signal-regulated kinase (ERK)1/2 in cardiomyocytes. The effects of AVP on these parameters were significantly inhibited by a selective vasopressin V1A receptor antagonist, OPC-21268, and were not observed in cardiomyocytes from mice lacking the vasopressin V1A receptor. In vivo cardiac hypertrophy in response to pressure overload was attenuated in vasopressin V1A receptor deficient (V1AR-KO) mice. Taken together, our data suggest that AVP promotes cardiomyocyte hypertrophy via the vasopressin V1A receptor, which is in part regulated by the pathway of ERK1/2 signaling. PMID- 17275807 TI - Primer-engineered multiplex PCR-RFLP for detection of MTHFR C677T, prothrombin G20210A and factor V Leiden mutations. AB - Single-nucleotide polymorphisms in the genes that code for coagulation factors V (factor V Leiden) and II (prothrombin, G20210A), as well as the methylenetetrahydrofolate reductase (MTHFR, C677T) gene, have been implicated in the majority of cases of hereditary thrombophilia. We have developed a multiplex PCR-RFLP assay based on MnlI endonuclease digestion for the simultaneous detection of mutations in the FV, FII, and MTHFR genes. Digested amplification products were analyzed by gel electrophoresis in a single gel lane and visualized by ethidium bromide. This approach is a rapid and convenient method, hence economic, that alternate to others described for the detection of FVL, G20210A and C677T mutations. PMID- 17275808 TI - Cholesteryl ester transfer protein gene polymorphisms are associated with coronary artery disease in Corsican population (France). AB - The aim of the present study was to investigate the association between coronary artery disease (CAD) and Cholesterol Ester Transfer Protein (CETP) (gaaa)n polymorphisms of the CETP gene in Central Corsica island (France). The study group was composed by 300 unrelated Corsican patients with angiographically documented CAD and 300 unrelated healthy blood donors. Significant differences were observed in the distribution of CETP (gaaa)n alleles between the groups under study (p=0.03; chi(2): 16.8, df: 8). The occurrence of a long allele (408 bp) was higher in cases (12%) than in control group (2%), showing a 6.75-fold increased risk for CAD in Corsica patients (p=0.0055; OR=6.750; 95% CIs=1.47 31.00). The correlation of this polymorphism with the lipid profile (cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides) in the patients group was determined. There was a significant association of the long alleles of CETP (gaaa)n with HDL-C levels. In the patient and in the control groups the LL genotypes had lower HDL-C compared with the SS and SL genotypes (p<0.0001). In summary our results suggest that the genetic variation at the CETP gene may play an important role in determining CAD in Corsican population. PMID- 17275809 TI - Targeting of nebulin fragments to the cardiac sarcomere. AB - Nebulin, a vertebrate skeletal muscle actin binding protein, plays an important role in thin filament architecture. Recently, a number of reports have indicated evidence for nebulin expression in vertebrate hearts. To investigate the ability of nebulin to interact with cardiac myofilaments, we have expressed nebulin cDNA fragments tagged with green fluorescent protein (GFP) in chicken cardiomyocytes and PtK2 cells. Nebulin fragments from both the superrepeats and single repeats were expressed minus and plus the nebulin linker. Nebulin fragment incorporation was monitored by fluorescent microscopy and compared with the distribution of actin, alpha-actinin and titin. Expression of nebulin N-terminal superrepeats displayed a punctate cytoplasmic distribution in PtK2 cells and cardiomyocytes. Addition of the nebulin linker to the superrepeats resulted in association of the punctate staining with the myofibrils. Nebulin C-terminal superrepeats plus and minus the linker localized with stress fibers of PtK2 cells and associated with the cardiac myofilaments at the level of the Z-line. Expression of the single repeats plus and minus the nebulin linker region resulted in both a Z-line distribution and an A-band distribution. These data suggest that N-terminal superrepeat nebulin modules are incapable of supporting interactions with the cardiac myofilaments; whereas the C-terminal nebulin modules can. The expression of the N-terminal or C-terminal superrepeats did not alter the distribution of actin, alpha-actinin or titin in either atrial or ventricular cultures. PMID- 17275810 TI - Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. AB - Bone morphogenetic protein (BMP), a member of the TGF-beta superfamily, is involved in development, morphogenesis, cell proliferation and apoptosis. Dysregulation of BMP signaling has been suggested in tumorigenesis. In an analysis of human colon normal mucosa and tumors at different stages by immunohistochemistry, we observed that the intensity of BMP-4 staining in late adenocarcinomas was stronger than that in normal mucosa and adenomas, while there was no difference in the staining of its receptors (BMPR-IA and BMPR-II) at all stages. The up-regulation of BMP-4 was further validated in another panel of tumor tissues by real-time RT-PCR, showing that BMP-4 mRNA levels in primary colonic carcinomas with liver metastasis were significantly higher than that in the matched normal mucosa. In order to understand the functional relevance of BMP 4 expression in colon cancer progression, BMP-4-overexpressing cell clones were generated from HCT116 cells. Overexpression of BMP-4 did not affect the HCT116 cell growth. The cells overexpressing BMP-4 became resistant to serum-starvation induced apoptosis and exhibited enhanced migration and invasion characteristics. Overexpression of BMP-4 changed cell morphology to invasive spindle phenotype and induced the expression and activity of urokinase plasminogen activator (uPA). These results indicate that BMP-4 confers invasive phenotype during progression of colon cancer. PMID- 17275811 TI - Identification of a population of cells with hematopoietic stem cell properties in mouse aorta-gonad-mesonephros cultures. AB - The aorta-gonad-mesonephros (AGM) region is a primary source of definitive hematopoietic cells in the midgestation mouse embryo. In cultures of dispersed AGM regions, adherent cells containing endothelial cells are observed first, and then non-adherent hematopoietic cells are produced. Here we report on the characterization of hematopoietic cells that emerge in the AGM culture. Based on the expression profiles of CD45 and c-Kit, we defined three cell populations: CD45(low) c-Kit(+) cells that had the ability to form hematopoietic cell colonies in methylcellulose media and in co-cultures with stromal cells; CD45(low) c-Kit( ) cells that showed a granulocyte morphology; CD45(high) c-Kit(low/-) that exhibited a macrophage morphology. In co-cultures of OP9 stromal cells and freshly prepared AGM cultures, CD45(low) c-Kit(+) cells from the AGM culture had the abilities to reproduce CD45(low) c-Kit(+) cells and differentiate into CD45(low) c-Kit(-) and CD45(high) c-Kit(low/-) cells, whereas CD45(low) c-Kit(-) and CD45(high) c-Kit(low/-) did not produce CD45(low) c-Kit(+) cells. Furthermore, CD45(low) c-Kit(+) cells displayed a long-term repopulating activity in adult hematopoietic tissue when transplanted into the liver of irradiated newborn mice. These results indicate that CD45(low) c-Kit(+) cells from the AGM culture have the potential to reconstitute multi-lineage hematopoietic cells. PMID- 17275812 TI - Fetal muscle-derived cells can repair dystrophic muscles in mdx mice. AB - We have previously reported that CD34(+) cells purified from mouse fetal muscles can differentiate into skeletal muscle in vitro and in vivo when injected into muscle tissue of dystrophic mdx mice. In this study, we investigate the ability of such donor cells to restore dystrophin expression, and to improve the functional muscle capacity of the extensor digitorum longus muscle (EDL) of mdx mice. For this purpose green fluorescent-positive fetal GFP(+)/CD34(+) cells or desmin(+)/(-)LacZ/CD34(+) cells were transplanted into irradiated or non irradiated mdx EDL muscle. Donor fetal muscle-derived cells predominantly fused with existing fibers. Indeed more than 50% of the myofibers of the host EDL contained donor nuclei delivering dystrophin along 80-90% of the length of their sarcolemma. The presence of significant amounts of dystrophin (about 60-70% of that found in a control wild-type mouse muscle) was confirmed by Western blot analyses. Dystrophin expression also outcompeted that of utrophin, as revealed by a spatial shift in the distribution of utrophin. At 1 month post-transplant, the recipient muscle appeared to have greater resistance to fatigue than control mdx EDL muscle during repeated maximal contractions. PMID- 17275813 TI - In vitro cultivation of Plasmodium falciparum: studies with modified medium supplemented with ALBUMAX II and various animal sera. AB - RPNI, a combination of three commercially available growth media (RPMI-1640, NCTC 135 and IMDM) has been found to support long term continuous cultivation of 3D7 strain of Plasmodium falciparum in the presence of 10% bovine calf serum. During the present study, the suitability of this medium was evaluated for the development of P. falciparum in the presence of horse, goat and rabbit sera as well as various concentrations of ALBUMAX II. RPNI medium supplemented with 10% bovine calf serum (RPNI-BCS) was used as control. The cultures were maintained in candle jars protocol and parasitaemia was monitored daily up to day 7. Horse, goat and rabbit sera all supported the development of P. falciparum. Horse serum gave best results in RPNI medium and supported continuous culture up to day 100. The parasitaemia in the presence of ALBUMAX was significantly higher in RPNI than in RPMI-1640. Addition of hypoxanthine in RPMI-1640 caused an increase in parasitaemia whereas no obvious advantage could be observed in RPNI. The findings exhibited that medium RPNI has an edge over conventional RPMI-1640 medium for in vitro cultivation of P. falciparum. PMID- 17275814 TI - Degradation of pteridine reductase 1 (PTR1) enzyme during growth phase in the protozoan parasite Leishmania donovani. AB - Pteridine reductase 1 (PTR1) is an essential enzyme of pterin and folate metabolism in the protozoan parasite Leishmania. The present work is focused on the degradation of PTR1 during growth phase in Leishmania donovani. Western blot analysis with PTR1-GFP transfected promastigotes revealed that PTR1 protein was degraded in the stationary phase of growth at the time when the parasites were undergoing metacyclogenesis. Fluorescence microscopy revealed cytoplasmic localization of GFP tagged protein extending to the flagellum in these stationary phase promastigotes, implying that degradation of the protein was not by the usual multivesicular tubule lysosome (MVT) pathway. A probable destruction box of nine amino acids Q63ADLSNVAK71 and possible lysine residue K156 was identified in L. donovani PTR1 to be the site for ubiquitin conjugation. This suggests that PTR1 degradation during the stationary phase of growth is mediated by the proteasome. This leads to lower levels of H4-biopterin, which favors metacyclogenesis, and subsequently results in a highly infective stage of the parasite. Therefore, this finding has importance to identify new target molecule like the proteasome for therapeutic intervention. PMID- 17275816 TI - The high-resolution NMR structure of a single-chain chimeric protein mimicking a SH3-peptide complex. AB - Here we present the high-resolution NMR structure of a chimera (SPCp41) between alpha-spectrin SH3 domain and the decapeptide p41. The tertiary structure mimics perfectly the interactions typically found in SH3-peptide complexes and is remarkably similar to that of the complex between the separate Spc-SH3 domain and ligand p41. Relaxation data confirm the tight binding between the ligand and SH3 part of the chimera. This chimera will serve as a tool for a deeper understanding of the relationship between structure and thermodynamics of binding using a combination of NMR, stability and site-directed mutagenesis studies, which can lead to an effective strategy for ligand design. PMID- 17275815 TI - Active Galpha(q) subunits and M3 acetylcholine receptors promote distinct modes of association of RGS2 with the plasma membrane. AB - RGS proteins accelerate the GTPase activity of heterotrimeric G proteins at the plasma membrane. Association of RGS proteins with the plasma membrane can be mediated by interactions with other membrane proteins and by direct interactions with the lipid bilayer. Here we use fluorescence recovery after photobleaching (FRAP) to characterize interactions between RGS2 and M3 acetylcholine receptors (M3Rs), Galpha subunits and the lipid bilayer. Active Galpha(q) and M3Rs both recruited RGS2-EGFP to the plasma membrane. RGS2-EGFP remained bound to the plasma membrane between interactions with active Galpha(q), but rapidly exchanged between membrane-associated and cytosolic pools when recruited by M3Rs. PMID- 17275817 TI - Eugenol inhibit 7,12-dimethylbenz[a]anthracene-induced genotoxicity in MCF-7 cells: Bifunctional effects on CYP1 and NAD(P)H:quinone oxidoreductase. AB - Typically, chemopreventive agents either inhibit the cytochrome P450s (CYPs) that are essential for the metabolism of carcinogens or induce phase II detoxifying enzymes. This study examined the chemopreventive effect of eugenol on 7,12 dimethylbenz[a]anthracene (DMBA)-induced DNA damage in MCF-7 cells. Eugenol inhibited the formation of the DMBA-DNA adduct in a dose dependent manner. CYP1A1 and CYP1B1 activity, which catalyze the biotransformation of DMBA, were strongly inhibited by eugenol. Eugenol also suppressed the CYP1A induction by DMBA through decreased aryl hydrocarbon receptor activation and subsequent DNA binding. Furthermore, eugenol increased the expression and activity of NAD(P)H:quinone oxidoreductase (QR), a major detoxifying enzyme for DMBA, through NF-E2 related factor2 binding to antioxidant response element in QR gene. Therefore, eugenol has a potent protective effect against DMBA-induced genotoxicity, presumably through the suppression of the DMBA activation and the induction of its detoxification. These results suggest that eugenol has potential as a chemopreventive. PMID- 17275818 TI - Involvement of membrane protein GDE2 in retinoic acid-induced neurite formation in Neuro2A cells. AB - We show that a glycerophosphodiester phosphodiesterase homolog, GDE2, is widely expressed in brain tissues including primary neurons, and that the expression of GDE2 in neuroblastoma Neuro2A cells is significantly upregulated during neuronal differentiation by retinoic acid (RA) treatment. Stable expression of GDE2 resulted in neurite formation in the absence of RA, and GDE2 accumulated at the regions of perinuclear and growth cones in Neuro2A cells. Furthermore, a loss-of function of GDE2 in Neuro2A cells by RNAi blocked RA-induced neurite formation. These results demonstrate that GDE2 expression during neuronal differentiation plays an important role for growing neurites. PMID- 17275819 TI - Evolutionary conservation of bursicon in the animal kingdom. AB - Bursicon bioactivity is essential for tanning of the exoskeleton and for wing spreading behavior that occur in newly emerged adult insects. Previously, we demonstrated that in the fruit fly, Drosophila melanogaster, bursicon exists as a heterodimeric cystine knot protein that activates the leucine-rich repeats containing G protein-coupled receptor 2 (DLGR2). By performing similarity based in silico searches in genomic and complementary DNA databases, we identified bursicon homologous sequences in several protostomian as well as deuterostomian invertebrates. In the genome of the honeybee, Apis mellifera, the coding regions for bursicon cystine knot subunits are organized in a genomic locus of approximately 4 kilobase pairs. Reverse transcription PCR analysis indicates that this region likely codes for two distinct bursicon cystine knot subunits. Our results illustrate the remarkable conservation of bursicon in invertebrate species and provide an avenue for functional analyses of this hormone in a wide range of animal species. PMID- 17275821 TI - Study of a risk-based piping inspection guideline system. AB - A risk-based inspection system and a piping inspection guideline model were developed in this study. The research procedure consists of two parts--the building of a risk-based inspection model for piping and the construction of a risk-based piping inspection guideline model. Field visits at the plant were conducted to develop the risk-based inspection and strategic analysis system. A knowledge-based model had been built in accordance with international standards and local government regulations, and the rational unified process was applied for reducing the discrepancy in the development of the models. The models had been designed to analyze damage factors, damage models, and potential damage positions of piping in the petrochemical plants. The purpose of this study was to provide inspection-related personnel with the optimal planning tools for piping inspections, hence, to enable effective predictions of potential piping risks and to enhance the better degree of safety in plant operations that the petrochemical industries can be expected to achieve. A risk analysis was conducted on the piping system of a petrochemical plant. The outcome indicated that most of the risks resulted from a small number of pipelines. PMID- 17275820 TI - Maternal glucocorticoid deficit affects hypothalamic-pituitary-adrenal function and behavior of rat offspring. AB - Detrimental consequences of prenatal stress include increased hypothalamic pituitary-adrenal (HPA) function, anxiety and depression-like behavior in adult offspring. To identify the role of maternal corticosterone milieu in the fetal programming of adult function, we measured these same behavioral and hormonal endpoints after maternal adrenalectomy (ADX) and replacement with normal or moderately high levels of corticosterone (CORT). Adult male and female offspring exhibited differing HPA responses to maternal ADX. In female offspring of ADX mothers, exaggerated plasma ACTH stress responses were reversed by the higher, but not the lower, dose of maternal CORT. In contrast, male offspring of both ADX and ADX dams with higher CORT replacement showed exaggerated ACTH stress responses. Hypothalamic glucocorticoid receptor (GR) expression was decreased in these latter groups, while hippocampal GR increased only in the ADX offspring. Activity of young offspring of ADX dams replaced with the higher dose of CORT decreased in the open field test of exploration/anxiety, while immobility behavior of adult offspring in the forced swim test of depression increased following maternal ADX or higher levels of CORT replacement. Interestingly, for some measures, none or moderately high CORT replacement resulted in similar deficits in this study. These findings are in accord with consequences of prenatal stress or prenatal dexamethasone exposure, suggesting that a common mechanism may underlie the effects of too low or too high maternal glucocorticoids on adult HPA function and behavior. PMID- 17275822 TI - Mobile robotic sensors for perimeter detection and tracking. AB - Mobile robot/sensor networks have emerged as tools for environmental monitoring, search and rescue, exploration and mapping, evaluation of civil infrastructure, and military operations. These networks consist of many sensors each equipped with embedded processors, wireless communication, and motion capabilities. This paper describes a cooperative mobile robot network capable of detecting and tracking a perimeter defined by a certain substance (e.g., a chemical spill) in the environment. Specifically, the contributions of this paper are twofold: (i) a library of simple reactive motion control algorithms and (ii) a coordination mechanism for effectively carrying out perimeter-sensing missions. The decentralized nature of the methodology implemented could potentially allow the network to scale to many sensors and to reconfigure when adding/deleting sensors. Extensive simulation results and experiments verify the validity of the proposed cooperative control scheme. PMID- 17275823 TI - Acute pulmonary edema secondary to long-term use of oral ritodrine in a woman with a triplet pregnancy. AB - A 28-year-old primigravida who had taken oral ritodrine for 5 months to stop premature uterine contractions and was admitted in labor in the 33rd week of pregnancy developed acute pulmonary edema after cesarean section. Although parenteral ritodrine is the beta-adrenergic agent used most extensively to treat premature labor, only 1 case of pulmonary edema associated with long-term use of oral ritodrine had been reported so far. The present report presents for the first time computed tomographic findings of acute pulmonary edema secondary to tocolytic therapy. PMID- 17275824 TI - Characterization of the RNA polymerase II and III complexes in Leishmania major. AB - Transcription of protein-coding genes in Leishmania major and other trypanosomatids differs from that in most eukaryotes and bioinformatic analyses have failed to identify several components of the RNA polymerase (RNAP) complexes. To increase our knowledge about this basic cellular process, we used tandem affinity purification (TAP) to identify subunits of RNAP II and III. Mass spectrometric analysis of the complexes co-purified with TAP-tagged LmRPB2 (encoded by LmjF31.0160) identified seven RNAP II subunits: RPB1, RPB2, RPB3, RPB5, RPB7, RPB10 and RPB11. With the exception of RPB10 and RPB11, and the addition of RPB8, these were also identified using TAP-tagged constructs of one (encoded by LmjF34.0890) of the two LmRPB6 orthologues. The latter experiments also identified the RNAP III subunits RPC1 (C160), RPC2 (C128), RPC3 (C82), RPC4 (C53), RPC5 (C37), RPC6 (C34), RPC9 (C17), RPAC1 (AC40) and RPAC2 (AC19). Significantly, the complexes precipitated by TAP-tagged LmRPB6 did not contain any RNAP I-specific subunits, suggesting that, unlike in other eukaryotes, LmRPB6 is not shared by all three polymerases but is restricted to RNAP II and III, while the LmRPB6z (encoded by LmjF25.0140) isoform is limited to RNAP I. Similarly, we identified peptides from only one (encoded by LmjF18.0780) of the two RPB5 orthologues and one (LmjF13.1120) of the two RPB10 orthologues, suggesting that LmRPB5z (LmjF18.0790) and LmRPB10z (LmjF13.1120) are also restricted to RNAP I. In addition to these RNAP subunits, we also identified a number of other proteins that co-purified with the RNAP II and III complexes, including a potential transcription factor, several histones, an ATPase involved in chromosome segregation, an endonuclease, four helicases, RNA splicing factor PTSR-1, at least two RNA binding proteins and several proteins of unknown function. PMID- 17275825 TI - An experimental evaluation of host specificity: the role of encounter and compatibility filters for a rhizocephalan parasite of crabs. AB - The encounter/compatibility paradigm of host specificity provides three qualitative pathways to the success or failure of a potential host-parasite interaction. It is usually impossible to distinguish between two of these (encounter and compatibility filters closed versus encounter filter open and compatibility filter closed) because unsuccessful infection attempts are difficult to observe in nature. We were able to open the encounter filter under experimental laboratory conditions. Our analytical system used the rhizocephalan barnacle, Sacculina carcini, a parasitic castrator of the European green crab, Carcinus maenas, and Pachygrapsus marmoratus, a native European crab that occurs with C. maenas but is not parasitized by S. carcini in nature. Penetration followed by unsuccessful infection of P. marmoratus crabs by parasitic barnacle larvae leaves a uniquely permanent record in the thoracic ganglion of the crabs. This provided us with a novel tool to quantify the encounter filter in a host parasite system in nature. We demonstrated, in the laboratory, that the compatibility filter was closed and that, in nature, even where barnacle larvae were present, the encounter filter was also effectively closed. The closure of both filters in nature explains the failure of this potential host-parasite interaction, an outcome favored by selection in both host and parasite. PMID- 17275826 TI - Efficiency of salivary gland invasion by malaria sporozoites is controlled by rapid sporozoite destruction in the mosquito haemocoel. AB - For successful transmission to the vertebrate host, malaria sporozoites must migrate from the mosquito midgut to the salivary glands. Here, using purified sporozoites inoculated into the mosquito haemocoel, we show that salivary gland invasion is inefficient and that sporozoites have a narrow window of opportunity for salivary gland invasion. Only 19% of sporozoites invade the salivary glands, all invasion occurs within 8h at a rate of approximately 200 sporozoites per hour, and sporozoites that fail to invade within this time rapidly die and are degraded. Then, using natural release of sporozoites from oocysts, we show that haemolymph flow through the dorsal vessel facilitates proper invasion. Most mosquitoes had low steady-state numbers of circulating sporozoites, which is remarkable given the thousands of sporozoites released per oocyst, and suggests that sporozoite degradation is a rapid immune process most efficient in regions of high haemolymph flow. Only 2% of Anopheles gambiae haemocytes phagocytized Plasmodium berghei sporozoites, a rate insufficient to explain the extent of sporozoite clearance. Greater than 95% of haemocytes phagocytized Escherichia coli or latex particles, indicating that their failure to sequester large numbers of sporozoites is not due to an inability to engage in phagocytosis. These results reveal the operation of an efficient sporozoite-killing and degradation machinery within the mosquito haemocoel, which drastically limits the numbers of infective sporozoites in the mosquito salivary glands. PMID- 17275827 TI - Relationship between the successful infection by entomopathogenic nematodes and the host immune response. AB - Reproduction of entomopathogenic nematodes requires that they escape recognition by a host's immune system or that they have mechanisms to escape encapsulation and melanization. We investigated the immune responses of larvae for the greater wax moth (Galleria mellonella), tobacco hornworm (Manduca sexta), Japanese beetle (Popillia japonica), northern masked chafer (Cyclocephala borealis), oriental beetle (Exomala orientalis) and adult house crickets (Acheta domesticus), challenged with infective juveniles from different species and strains of entomopathogenic nematodes. The in vivo immune responses of hosts were correlated with nematode specificity and survival found by infection assays. In P. japonica, 45% of injected infective juveniles from Steinernema glaseri NC strain survived; whereas the hemocytes from the beetle strongly encapsulated and melanized the Heterorhabditis bacteriophora HP88 strain, S. glaseri FL strain, Steinernema scarabaei and Steinernema feltiae. Overall, H. bacteriophora was intensively melanized in resistant insect species (E. orientalis, P. japonica and C. borealis) and had the least ability to escape the host immune response. Steinernema glaseri NC strain suppressed the immune responses in susceptible hosts (M. sexta, E. orientalis and P. japonica), whereas S. glaseri FL strain was less successful. Using an in vitro assay, we found that hemocytes from G. mellonella, P. japonica, M. sexta and A. domestica recognized both nematode species quickly. However, many S. glaseri in M. sexta and H. bacteriophora in G. mellonella escaped from hemocyte encapsulation by 24h. These data indicate that, while host recognition underlies some of the differences between resistant and susceptible host species, escape from encapsulation following recognition can also allow successful infection. Co-injected surface-coat proteins from S. glaseri did not protect H. bacteriophora in M. sexta but did protect H. bacteriophora in E. orientalis larva; therefore, surface coat proteins do not universally convey host susceptibility. Comparisons of surface coat proteins by native and SDS-PAGE demonstrated different protein compositions between H. bacteriophora and S. glaseri and between the two strains of S. glaseri. PMID- 17275828 TI - Rosuvastatin regulates vascular smooth muscle cell phenotypic modulation in vascular remodeling: role for the urokinase receptor. AB - The urokinase (uPA)/urokinase receptor (uPAR) multifunctional system is an important mediator of migration and proliferation of vascular smooth muscle cells (VSMC). However, whether uPA/uPAR-directed mechanisms are involved in the beneficial effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on vascular remodeling remains unexplored. In this study, we have investigated the effect of the hydrophilic statin rosuvastatin on neointimal remodeling, and the role of uPAR. Using an ex vivo organ and in vitro cell culture models we demonstrate that rosuvastatin decreases injury-induced neointima formation and proliferation of medial VSMC in porcine coronary arteries, as well as migration and proliferation of human coronary VSMC. Studies on the underlying mechanisms show that rosuvastatin impairs VSMC transition from their physiological contractile to the pathophysiological synthetic phenotype. These effects are mediated, at least in part, via uPAR, as confirmed by means of rosuvastatin directed uPAR expression and uPAR silencing in both models. Our findings provide evidence that rosuvastatin modulates VSMC phenotypic changes and subsequently their proliferation and migration, and indicate the important role for uPAR in these processes. This mechanism contributes to the beneficial non-lipid lowering effect of rosuvastatin on negative vascular remodeling. PMID- 17275829 TI - Learning to walk with a robotic ankle exoskeleton. AB - We used a lower limb robotic exoskeleton controlled by the wearer's muscle activity to study human locomotor adaptation to disrupted muscular coordination. Ten healthy subjects walked while wearing a pneumatically powered ankle exoskeleton on one limb that effectively increased plantar flexor strength of the soleus muscle. Soleus electromyography amplitude controlled plantar flexion assistance from the exoskeleton in real time. We hypothesized that subjects' gait kinematics would be initially distorted by the added exoskeleton power, but that subjects would reduce soleus muscle recruitment with practice to return to gait kinematics more similar to normal. We also examined the ability of subjects to recall their adapted motor pattern for exoskeleton walking by testing subjects on two separate sessions, 3 days apart. The mechanical power added by the exoskeleton greatly perturbed ankle joint movements at first, causing subjects to walk with significantly increased plantar flexion during stance. With practice, subjects reduced soleus recruitment by approximately 35% and learned to use the exoskeleton to perform almost exclusively positive work about the ankle. Subjects demonstrated the ability to retain the adapted locomotor pattern between testing sessions as evidenced by similar muscle activity, kinematic and kinetic patterns between the end of the first test day and the beginning of the second. These results demonstrate that robotic exoskeletons controlled by muscle activity could be useful tools for testing neural mechanisms of human locomotor adaptation. PMID- 17275830 TI - Automated, on-line membrane extraction. AB - Over the last few years, membranes have been used to develop new approaches in analytical extraction, concentration and cleanup. An important advantage of membrane processes is that the sample and the extraction phase can be continuously brought into contact without physical mixing, and may be directly interfaced to an analytical instrument. This provides the basis for automated, real-time monitoring. Membrane extraction has been applied to a wide range of organic and inorganic analytes, and has been directly interfaced with chromatography, spectroscopy and mass spectrometry. Implementations of membrane extraction are diverse, encompassing different types of membranes, module designs and configurations. This review highlights some of these, and particularly the unique capabilities in automated, and on-line measurements. PMID- 17275831 TI - Comparison of available analytical methods to measure trans-octadecenoic acid isomeric profile and content by gas-liquid chromatography in milk fat. AB - Accurate quantification of trans-fatty acids (TFAs) could be achieved by infrared spectroscopy or by gas-liquid chromatography (GLC). Accurate quantification by GLC should be achieved using specific highly polar capillary columns such as 100 m CP-Sil 88 or equivalent. A pre-fractionation of cis and trans-fatty acids could be performed by silver-ion thin-layer chromatography (Ag-TLC), silver-ion solid phase extraction (Ag-SPE), or by high-performance liquid-chromatography (HPLC). A pre-fractionation step allows accurate determination of the isomeric profile but it is not essential to achieve quantification of total trans-18:1 isomers nor to determine the level of vaccenic (trans-11 18:1) acid in dairy fat. TFA content could also be calculated in milk fat based on the TAG profile determined by GLC. In this paper, different GLC methods suitable to measure the total of trans-18:1 isomers, vaccenic acid and trans-18:1 acid isomeric distribution in milk fat were compared. Pre-separation of cis- and trans-18:1 isomers by Ag-TLC followed by GLC analysis under optimal conditions was selected as the reference method. Results obtained using alternative methods including pre-separation by HPLC followed by GLC analysis, direct quantification by GLC or calculation from the triacylglycerol (TAG) profile were compared to data acquired using the reference method. Results showed that accurate quantification of total trans-18:1 isomers and vaccenic acid could be achieved by direct quantification by GLC under optimal chromatographic conditions. This method represents a very good alternative to Ag TLC followed by GLC analysis. On the other hand, we showed that pre-fractionation of fatty acid methyl esters (FAMEs) by HPLC represents a good alternative to Ag TLC, even if some minor isomers are not selectively purified using this procedure. PMID- 17275832 TI - The statistical theory of linear capillary chromatography with uniform stationary phase. AB - Based on the random walk model and probability theory, general relations between the moments of column residence time and the moments of step sojourn time and step displacement are established. And starting from the mass-balances principle of solute molecules in the mobile and stationary phases, the moments of step sojourn time and step displacement are derived and expressed in terms of the basic parameters. Substituting the step moments into the general relations, the moments of column residence time are then obtained. The expression of retention time is completely identical to the well-known, the expressions of second moment or HETP unite and generalize various expressions of stochastic theory and mass balance theory, and the third and forth moments are given in more exact form. PMID- 17275833 TI - Non-suppurative meningoencephalitis of unknown origin in cats and dogs: an immunohistochemical study. AB - Non-suppurative meningoencephalitis of unknown cause is a frequent finding in dogs and cats. Fifty-three dogs and 33 cats with non-suppurative meningoencephalitis of unknown aetiology were examined immunohistochemically for 18 different infectious agents, including viruses, bacteria and prion protein(Sc). In 14 (26%) of the dogs and 13 (39%) of the cats a causative agent was identified in the central nervous system (CNS), two dogs and one cat giving positive results for two infectious agents simultaneously. The study revealed infections with known causative agents (porcine herpes virus 1, feline infectious peritonitis virus, Escherichia coli) and a new disease pattern of parvovirus infection in the CNS of dogs and cats. Infection of the CNS with feline leukaemia virus was found in a cat. Five dogs and four cats gave positive results for West Nile virus (WNV) antigen. In one dog, canine parainfluenza virus antigen was detected in the brain. Four dogs and four cats gave positive results for encephalomyocarditis virus (EMCV). The significance of the detection of WNV and EMCV antigen requires further study. The aetiology remained undetermined in 39 dogs (74%) and 20 cats (61%). Although it is possible that non-infectious causes play a more important role than previously thought, infections with hitherto unrecognized agents cannot be ruled out. PMID- 17275834 TI - Automated real-time measurements of leukocyte chemotaxis. AB - We have previously described an automated system (ECIS/taxis) for measuring chemotactic movement of Dictyostelium amoebae in a folic acid gradient [Hadjout, N., Laevsky, G., Knecht, D.A. and Lynes, M.A., 2001. Automated real-time measurement of chemotactic cell motility. Biotechniques 31, 1130-1138.]. In the ECIS/taxis system, cells migrate in an under-agarose environment, and their position is monitored by determining the impedance change caused by cells crawling onto the surface of an electrode. In this report, we show that chemotaxis of primary and immortalized leukocytes in response to complement (C5a) could be measured using the ECIS/taxis system. Several modifications to the design of the target electrode were tested, and a linear electrode perpendicular to the direction of movement was found to increase the sensitivity and reliability of the assay. Using the optimized ECIS/taxis assay, the dose response of neutrophils and WBC 265-9C cells was established and compared to the Boyden chamber assay. The ECIS/taxis assay system can be used to compare the movement of different cell types, to assess the effect of complex chemotactic gradients, or to determine the effects of pharmaceuticals on chemotactic motility. PMID- 17275835 TI - Structure and action of a C-C bond cleaving alpha/beta-hydrolase involved in nicotine degradation. AB - The enzyme 2,6-dihydroxy-pseudo-oxynicotine hydrolase from the nicotine degradation pathway of Arthrobacter nicotinovorans was crystallized and the structure was determined by an X-ray diffraction analysis at 2.1 A resolution. The enzyme belongs to the alpha/beta-hydrolase family as derived from the chain fold and from the presence of a catalytic triad with its oxyanion hole at the common position. This relationship assigns a pocket lined by the catalytic triad as the active center. The asymmetric unit contains two C(2)-symmetric dimer molecules, each adopting a specific conformation. One dimer forms a more spacious active center pocket and the other a smaller one, suggesting an induced-fit. All of the currently established C-C bond cleaving alpha/beta-hydrolases are from bacterial meta-cleavage pathways for the degradation of aromatic compounds and cover their active center with a 40 residue lid placed between two adjacent strands of the beta-sheet. In contrast, the reported enzyme shields its active center with a 110 residue N-terminal domain, which is absent in the meta-cleavage hydrolases. Since neither the substrate nor an analogue could be bound in the crystals, the substrate was modeled into the active center using the oxyanion hole as a geometric constraint. The model was supported by enzymatic activity data of 11 point mutants and by the two dimer conformations suggesting an induced fit. Moreover, the model assigned a major role for the large N-terminal domain that is specific to the reported enzyme. The proposal is consistent with the known data for the meta-cleavage hydrolases although it differs in that the reaction does not release alkenes but a hetero-aromatic compound in a retro Friedel-Crafts acylation. Because the hydrolytic water molecule can be assigned to a geometrically suitable site that can be occupied in the presence of the substrate, the catalytic triad may not form a covalent acyl-enzyme intermediate but merely support a direct hydrolysis. PMID- 17275836 TI - TFB1 or TFB2 is sufficient for Thermococcus kodakaraensis viability and for basal transcription in vitro. AB - Archaeal RNA polymerases (RNAPs) are most similar to eukaryotic RNAP II (Pol II) but require the support of only two archaeal general transcription factors, TBP (TATA-box binding protein) and TFB (archaeal homologue of the eukaryotic general transcription factor TFIIB) to initiate basal transcription. However, many archaeal genomes encode more than one TFB and/or TBP leading to the hypothesis that different TFB/TBP combinations may be employed to direct initiation from different promoters in Archaea. As a first test of this hypothesis, we have determined the ability of RNAP purified from Thermococcus kodakaraensis (T.k.) to initiate transcription from a variety of T.k. promoters in vitro when provided with T.k. TBP and either TFB1 or TFB2, the two TFBs encoded in the T.k. genome. With every promoter active in vitro, transcription initiation occurred with either TFB1 or TFB2 although the optimum salt concentration for initiation was generally higher for TFB2 (approximately 250 mM K(+)) than for TFB1 (approximately 200 mM K(+)). Consistent with this functional redundancy in vitro, T.k. strains have been constructed with the TFB1- (tfb1; TK1280) or TFB2- (tfb2; TK2287) encoding gene deleted. These mutants exhibit no detectable growth defects under laboratory conditions. Domain swapping between TFB1 and TFB2 has identified a central region that contributes to the salt sensitivity of TFB activity, and deleting residues predicted to form the tip of the B-finger region of TFB2 had no detectable effects on promoter recognition or transcription initiation but did eliminate the production of very short (< or =5 nt) abortive transcripts. PMID- 17275837 TI - A structural comparison of inhibitor binding to PKB, PKA and PKA-PKB chimera. AB - Although the crystal structure of the anti-cancer target protein kinase B (PKBbeta/Akt-2) has been useful in guiding inhibitor design, the closely related kinase PKA has generally been used as a structural mimic due to its facile crystallization with a range of ligands. The use of PKB-inhibitor crystallography would bring important benefits, including a more rigorous understanding of factors dictating PKA/PKB selectivity, and the opportunity to validate the utility of PKA-based surrogates. We present a "back-soaking" method for obtaining PKBbeta-ligand crystal structures, and provide a structural comparison of inhibitor binding to PKB, PKA, and PKA-PKB chimera. One inhibitor presented here exhibits no PKB/PKA selectivity, and the compound adopts a similar binding mode in all three systems. By contrast, the PKB-selective inhibitor A-443654 adopts a conformation in PKB and PKA-PKB that differs from that with PKA. We provide a structural explanation for this difference, and highlight the ability of PKA-PKB to mimic the true PKB binding mode in this case. PMID- 17275838 TI - Interaction of discoidin domain receptor 1 with collagen type 1. AB - Discoidin domain receptor 1 (DDR1) is a widely expressed tyrosine kinase receptor which binds to and gets activated by collagens including collagen type 1. Little is understood about the interaction of DDR1 with collagen and its possible functional implications. Here, we elucidate the binding pattern of the DDR1 extracellular domain (ECD) to collagen type 1 and its impact on collagen fibrillogenesis. Our in vitro assays utilized DDR1-Fc fusion proteins, which contain only the ECD of DDR1. Using surface plasmon resonance, we confirmed that further oligomerization of DDR1-Fc (by means of anti-Fc antibody) greatly enhances its binding to immobilized collagen type 1. Single-molecule imaging by means of atomic force microscopy revealed that DDR1 oligomers bound at overlapping or adjacent collagen molecules and were nearly absent on isolated collagen molecules. Interaction of DDR1 oligomers with collagen was found to modulate collagen fibrillogenesis both in vitro and in cell-based assays. Collagen fibers formed in the presence of DDR1 had a larger average diameter, were more cross-linked and lacked the native banded structure. The presence of DDR1 ECD resulted in "locking" of collagen molecules in an incomplete fibrillar state both in vitro and on surfaces of cells overexpressing DDR1. Our results signify an important functional role of the DDR1 ECD, which occurs naturally in kinase-dead isoforms of DDR1 and as a shedded soluble protein. The modulation of collagen fibrillogenesis by the DDR1 ECD elucidates a novel mechanism of collagen regulation by DDR1. PMID- 17275839 TI - The crystal structure of the extracellular domain of the inhibitor receptor expressed on myeloid cells IREM-1. AB - The immune receptors expressed on myeloid cells (IREM) are type I transmembrane proteins encoded on human chromosome 17 (17q25.1), whose function is believed to be important in controlling inflammation. To date, three IREM receptors have been identified. IREM-1 functions as an inhibitory receptor, whereas IREM-2 and IREM-3 serve an activating function. Here, we report the crystal structure of IREM-1 extracellular domain at 2.6 A resolution. The overall fold of IREM-1 resembles that of a V-type immunoglobulin domain, and reveals overall close homology with immunoglobulin domains from other immunoreceptors such as CLM-1, TREM-1, TLT-1 and NKp44. Comparing the surface electrostatic potential and hydrophobicity of IREM-1 with its murine homologous CLM-1, we observed unique structural properties for the complementary determining region of IREM-1, which suggests that they may be involved in recognition of the IREM-1 ligand. Particularly interesting is the structural conformation and physical properties of the antibody's equivalent CDR3 loop, which we show to be a structurally variable region of the molecule and therefore could be the main structural determinant for ligand discrimination and binding. In addition, the analysis of the IREM-1 structure revealed the presence of four structurally different cavities. Three of these cavities form a continuous hydrophobic groove on the IREM-1 surface, which point to a region of the molecule capable of accommodating potential ligands. PMID- 17275840 TI - Electronic source materials in clinical research: acceptability and validity of symptom self-rating in major depressive disorder. AB - OBJECTIVES: Clinical research projects gather large amounts of data. Typically, information is captured on paper source documents for later transcription to an electronic format, where responses can be checked, and errors, omissions, and inconsistencies can be resolved. These steps contribute delays, cost, and complexity to clinical research, particularly in large-scale multi-site investigations. To address these issues, we used a mobile computing device with a touch-screen display ("tablet PC") to capture clinical data from depressed patients directly into electronic format. We then examined ease of use, the equivalence of responses between paper and electronic methods, and the acceptability of the tablet PC for this clinical population. SETTINGS: Outpatient clinics at four medical centers. METHODS: 80 adults with major depressive disorder (MDD) completed the 16-item Quick Inventory of Depressive Symptomatology -Self-Rated (QIDS-SR(16)), using both traditional paper forms and an electronic representation of the same questions; participants also completed a survey to evaluate their experience. RESULTS: QIDS-SR(16) responses from paper and electronic versions were highly correlated (mean total: 15.3 (SD=5.2) electronic vs. 15.1 (SD=5.2) paper format), and showed high inter-rating reliability for overall score (intra-class correlation 0.987 (with a 95%CI [0.979,0.992])) and high degree of association for individual symptom items. Participants found both methods acceptable and overall found the electronic implementation easier to use. CONCLUSIONS: QIDS-SR(16) values collected electronically from research participants were equivalent to those collected using traditional paper self assessment forms. Participants with MDD found the tablet PC version to be acceptable and easier to use than the paper forms. PMID- 17275841 TI - Exposure to bright light is associated with positive social interaction and good mood over short time periods: A naturalistic study in mildly seasonal people. AB - Bright light is used to treat winter depression and might also have positive effects on mood in some healthy individuals. We examined possible links between bright light exposure and social interaction using naturalistic data. For 20 days in winter and/or summer, 48 mildly seasonal healthy individuals wore a light meter at the wrist and recorded in real-time their behaviours, mood, and perceptions of others during social interactions. Possible short-term effects of bright light were examined using the number of minutes, within any given morning, afternoon or evening, that people were exposed to light exceeding 1000 lux (average: 19.6min). Social interactions were labelled as having occurred under conditions of no, low or high bright light exposure. Independent of season, day, time, and location, participants reported less quarrelsome behaviours, more agreeable behaviours and better mood when exposed to high but not low levels of bright light. Given that the effects were seen only when exposure levels were above average, a minimum level of bright light may be necessary for its positive effects to occur. Daily exposure levels were generally low in both winter and summer. Spending more time outdoors and improving indoor lighting may help optimize everyday social behaviour and mood across seasons in people with mild seasonality. PMID- 17275842 TI - Beneficial effects of phosphatidylcholine during hindlimb reperfusion. AB - BACKGROUND: Microcirculatory dysfunctions and mast cell (MC) reactions play important roles in hypoxic tissue injuries. The aims of this study were to characterize the effects of hindlimb ischemia-reperfusion (I-R) on the periosteal microcirculation and to define the consequences of systemic phosphatidylcholine (PC) therapy during this condition. MATERIALS AND METHODS: Microcirculatory changes were visualized by means of fluorescence intravital videomicroscopy in anesthetized Wistar rats. There was 60 min of complete hindlimb ischemia followed by a 180-min reperfusion in the presence of PC treatment (50 mg/kg i.v.; in the second 10 min of reperfusion) or vehicle. Further two groups served as vehicle- or PC-treated sham-operated controls. The proportion of degranulated MCs and the leukocyte accumulation (myeloperoxidase, MPO assay) were determined in muscle biopsies. RESULTS: I-R significantly increased the muscle MPO activity (from 14.94 to 63.45 mU/mg) and the proportion of degranulated MCs (to 82.5%). The periosteal capillary RBC velocity (RBCV) and the functional capillary density (FCD) had decreased, while the primary and secondary leukocyte-endothelial cell interactions had increased by the end of reperfusion (rolling from 20.8 to 40.0%, and firm adherence from 254 to 872 mm(-2)). PC treatment decreased the leukocyte rolling and sticking, preserved the FCD and improved the RBCV. The MC degranulation and MPO activity diminished significantly in the muscle layer. CONCLUSIONS: PC administration improves I-R-induced periosteal microcirculatory dysfunctions and ameliorates secondary inflammatory reactions. Systemic PC treatment could offer a potential treatment modality during hypoperfusion or inflammatory conditions of the bones. PMID- 17275843 TI - In memoriam: a tribute to dr. Owen H. Wangensteen, the greatest teacher of surgery during the 20th century (1898-1981). AB - My philosophy regarding teaching has been formulated primarily by my close personal relationship with my beloved mentor, Dr. Owen Wangensteen, Professor and Chairman of the Department of Surgery at the University of Minnesota, who is recognized as the greatest teacher of surgery during this last century. By 1930, he had become Chairman of the Department of Surgery of the University of Minnesota Health Sciences Center, a position he held for 37[1/2] years. He transformed the University of Minnesota into a great center for surgery and attracted a group of brilliant young surgeons to do research on impossible problems. His lifelong recognition of the relevance of basic science and the insight to be derived from research in the training of young surgeons created the milieu and opportunities for great surgical achievements. During the period of almost 40 years in which he served as Chairman of the Department of Surgery, he became the greatest surgical educator of the 20th century. The future academic careers for his residents were indeed impressive: 38 became the department chairs; 31 accepted positions as division heads of their departments; 72 were directors of training programs; 110 became full professors; and 18 had appointments as associate professors. In this favorable environment uncluttered by the cobwebs of tradition, significant developments in surgery were forthcoming: open heart surgery; the heart-lung machine; cardiac pacemaker; conservative management of intestinal obstruction; heart, pancreatic, and intestinal transplantation and metabolic surgery for weight loss as well as elevated blood cholesterol; and revolutionary advances in wound repair. PMID- 17275844 TI - VEGF is important for early liver regeneration after partial hepatectomy. AB - BACKGROUND: The aim of the study was to determine the role of Vascular Endothelial Growth Factor (VEGF) on the microvasculature and on angiogenetic gene expression after partial hepatectomy (PH) in the rat model. METHODS: To determine the effect of exogenous and endogenous VEGF after PH, rats were subjected to 70% PH and treated either with VEGF, anti-VEGF or NaCl. Postoperatively (3-168 h), vessel density (VD), vessel diameter (VDi), and intersinusoidal space, liver body weight ratio (LBR), hepatic proliferation and biochemical markers were assessed. To further elucidate the underlying molecular mechanisms hepatic gene expression was determined by customized cDNA arrays and quantitative RT-PCR. RESULTS: In the VEGF group, VD, VDi, and LBR were significantly increased compared with anti-VEGF or controls. Blockage of endogenous VEGF led to a marked increase of biochemical markers. Anti-VEGF almost completely suppressed and VEGF markedly enhanced hepatic proliferation in the first 24 h after surgery. This was associated with a modulation of cell cycle control genes (PC4, Gadd45a, Tis21/BTG2), v-jun, and CD14 by VEGF. CONCLUSIONS: VEGF plays an important role in liver regeneration and this may be due in part through its effects on neovascularization. Whether it may, when given therapeutically, represent a strategy to optimize liver regeneration in problematic patients needs to be clarified. PMID- 17275845 TI - Low-dose phosphodiesterase inhibition improves responsiveness to inhaled nitric oxide in isolated lungs from endotoxemic rats. AB - BACKGROUND: Inhalation of nitric oxide (NO) and inhibition of phosphodiesterase type 5 (PDE5) selectively dilate the pulmonary circulation in patients with acute lung injury (ALI) associated with pulmonary hypertension. PDE5 inhibitors administered at doses that decrease pulmonary artery pressures have been shown to worsen arterial oxygenation. We investigated the efficacy of doses of PDE5 inhibitors that do not reduce pulmonary artery pressure alone (subthreshold doses) to improve the response to inhaled NO in an animal model of ALI. MATERIALS AND METHODS: Adult Sprague-Dawley rats were pre-treated with 0.5 mg/kg Escherichia coli 0111:B4 endotoxin and 16 to 18 h later, their lungs were isolated perfused and ventilated. The thromboxane mimetic U46619 was used to induce pulmonary hypertension. After the determination of subthreshold doses of two different PDE5 inhibitors, either 50 microg zaprinast or 10 ng sildenafil was added to the perfusate and the decrease of pulmonary artery pressure measured in the presence and absence of inhaled NO. RESULTS: In the presence of 4 or 10 ppm NO, zaprinast (-1.6 +/- 0.4 and -2.9 +/- 0.6 mmHg, respectively) and sildenafil ( 1.9 +/- 0.4 and -2.4 + 0.3 mmHg, respectively) improved responsiveness to inhaled NO compared to lungs from rats treated with LPS only (0.7 +/- 0.1 and -1.0 +/- 0.1 mmHg, respectively; P<0.05). Neither zaprinast nor sildenafil prolonged the pulmonary vasodilatory response to inhaled NO. CONCLUSIONS: Subthreshold doses of PDE5 inhibitors improved responsiveness to inhaled NO. Combining inhaled NO with subthreshold doses of PDE5 inhibitors may offer a therapeutic strategy with minimal side-effects in ALI associated with pulmonary hypertension. PMID- 17275846 TI - Statin pre-treatment protects brain against focal cerebral ischemia in diabetic mice. AB - BACKGROUND: Cerebrovascular diseases and other vascular complications are common and cause considerable mortality and morbidity in diabetes mellitus. Recent studies suggest that statins reduce the incidence of stroke in diabetic as well as non-diabetic patients. The outcome of stroke is shown to be worse in diabetics. However, the effect of statins on the outcome of stroke occurring in diabetics is not clear. The purpose of this study was to investigate the effect of pre-treatment with statins on focal cerebral ischemia in diabetic mice. MATERIALS AND METHODS: Swiss albino mice were randomized into two groups. Diabetes was induced in the first group by intravenous streptozotosin injection. The second group served as non-diabetic. After 4 weeks, half of the mice in diabetic and non-diabetic groups were randomized to receive intraperitoneal simvastatin 1 mg/kg/day or saline treatment for 14 days. Subsequently, mice were subjected to 90 min of proximal middle cerebral artery occlusion and 24 h of reperfusion. Sham-operation was also performed for each group. After 24 h of reperfusion, neurological deficits were scored and the infarct volume was measured on Nissl stained brain sections. RESULTS: Infarct volume (median, interquartile range) was significantly increased in the diabetic group (60.7 mm(3)) compared to non-diabetic group (53.4 mm(3)). Statin pre-treatment significantly reduced the infarct volume (to 40.4; 33.5 mm(3), respectively) and neurological disability scores both in diabetic and non-diabetic groups. CONCLUSIONS: These data suggest that diabetes aggravates the ischemic damage after focal cerebral ischemia and statin pre-treatment protects the brain in diabetic as well as healthy animals. Statin treatment may favorably affect stroke outcome in diabetic patients in addition to decreasing stroke incidence. PMID- 17275847 TI - Inhibition of heme oxygenase-1 protects against tissue injury in carbon tetrachloride exposed livers. AB - BACKGROUND/AIMS: During the metabolism of the hepatotoxin carbon tetrachloride (CCl(4)) by cytochrome P450, heme, and free radicals are released. Heme oxygenase (HO-1) is an enzyme that is induced by heme as well as oxidative stress and has been reported to be involved in mediating protection against toxic liver injury. The purpose of the present study was to specify the role of HO-1 in CCl(4) hepatotoxicity. METHODS AND RESULTS: We could demonstrate an up-regulation of HO 1 protein in CCl(4)-exposed liver tissue that reaches its maximum after 6 to 12 h, along with intrahepatic leukocyte accumulation and tissue injury. When animals were pretreated with hemin for augmentation of HO-1 expression, CCl(4)-exposure was associated with a reduction of intrahepatic leukocyte accumulation, while inhibition of CCl(4)-induced HO-1 expression by tin protoporphyrin-IX (SnPP-IX) enhanced leukocytic response. Of interest, however, liver morphology, transaminases, and bile flow as parameters of hepatocellular integrity and excretory function did not concur with reduced leukocyte numbers in the hepatic microcirculation, and revealed best organ function and tissue preservation in case of HO-1 inhibition by SnPP-IX. In contrast, hemin-treated CCl(4)-exposed livers demonstrated pathologic enzyme release and cholestasis. CONCLUSIONS: Taken together, inhibition of HO-1 in CCl(4)-hepatotoxicity protected the liver, while higher HO-1 activity harmed liver tissue, most probably due to interference of the HO-1 pathway with CCl(4)-dependent metabolism via cytochrome P450 and heme overload-associated toxicity. PMID- 17275849 TI - Is cerebral autoregulation impaired in Parkinson's disease? A transcranial Doppler study. AB - Orthostatic hypotension (OH) is one of the many autonomic disturbances observed in Parkinson's disease (PD). It has been debated whether an additional impairment of cerebral autoregulation (CA) in PD patients may exacerbate the consequences of OH upon brain perfusion. We assessed CA in PD patients and the potential influence of dopaminergic agents. CA was determined by means of transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) at rest and during a thigh cuff release test inducing a systemic blood pressure (BP) drop. Fourteen patients were investigated when taking their usual dopaminergic medication and after drug discontinuation for 12 h. A control group was composed of 11 age matched subjects (CS). In comparison with PD patients, CS presented a significantly higher increase of the mean cerebral blood flow velocities in the MCA after the BP drop. Mean velocities were increased above the initial values in all CS, whereas a flattened curve was observed in PD patients. No significant differences could be further observed between the PD patients regarding the BP, the cerebrovascular resistance, the heart rate and the pulsatility index. These results provide evidence of an impaired cerebral autoregulation in PD patients which appears independent of dopaminergic treatment. PMID- 17275848 TI - In vivo observation of leukocyte-endothelium interaction in ischemia reperfusion injury with the dorsal window chamber and the effects of pentoxifylline on reperfusion injury. AB - OBJECTIVE: Ischemia reperfusion injury can cause failure in microsurgical operations. Interaction between leukocytes and endothelium is recognized as an integral step in ischemia reperfusion injury. Pentoxifylline is a methylxanthine derivative that has pharmacological properties that can be beneficial in ischemia reperfusion injury. The aim of this study was to investigate the in vivo effect of pentoxifylline on leukocyte-endothelium interaction in ischemia reperfusion injury. METHODS: Intravital fluorescent microscopy was used to observe leukocyte endothelium interaction in a "dorsal window chamber" model. Twenty-eight postcapillary veins were analyzed in group 1, and twenty-two in group 2. Group 1 received 25 mg/kg pentoxifylline 20 min before reperfusion. Group 2 received an equivalent volume of 0.9% saline at the same time. The period of ischemia was 4 h. RESULTS: Quantification of leukocyte 'sticking' and 'rolling' was done before ischemia and at 30, 60, and 120 min after reperfusion. Offline video analysis was used for evaluating the results. Statistical evaluation showed that pentoxifylline significantly attenuated leukocyte 'sticking' and 'rolling' in postcapillary venules. It was also effective in preventing 'no-reflow' when compared with the control group. CONCLUSION: These results indicate pentoxifylline diminishes leukocyte-endothelium interaction, and may have a therapeutic role in preventing ischemia reperfusion injury in microsurgical operations. PMID- 17275851 TI - Lipid domain boundaries as prebiotic catalysts of peptide bond formation. AB - To address central problems in the origin of life such as the formation of linear polymers composed of only a small number of types of molecules, we have modeled the distribution of peptides in lipid monolayers. We show that short peptides and amino acids accumulate at the boundary between lipid domains, and that the concentration towards the boundary is higher the longer the peptide. We invoke a constraint on diffusion to one dimension as well as on orientation to suggest that polymerization of peptides is more likely to occur at the domain boundary than within domains or in the bulk phase. In a simple model, in which polymerization is taken to occur only at the boundary, we show that the equilibrium distribution of polymer lengths is shifted towards longer peptides. Since the reaction is occurring in a partially non-aqueous environment, hydrolysis is reduced and condensation increased to yield a significant polymerization. We show also that the free energy change from the redistribution of peptides within domains is sufficient to drive the formation of the peptide bond. PMID- 17275850 TI - Increased amyloid beta protein levels in children and adolescents with Down syndrome. AB - BACKGROUND: Persons with Down syndrome (DS) (40 years and older) have neuropathological changes characteristic of Alzheimer disease (AD). Soluble forms of amyloid beta (Abeta) peptide generated from amyloid precursor protein (APP) end at C-terminal residues 40 and 42. The presence of the apolipoprotein E (ApoE) epsilon4 allele is a significant risk factor for the development of sporadic AD. Although preliminary studies have shown an association of plasma Abeta42 and ApoE epsilon4 allele in older persons with DS who have dementia, the relationship between plasma Abeta40 and Abeta42 levels and ApoE phenotypes in children with DS has not been examined. Inflammation might play a role in the growth of DS brains. Neopterin is an immune activation marker for the cell-mediated immune response. OBJECTIVE: To examine the levels of plasma Abeta40, Abeta42, and neopterin in children or adolescents with DS or controls. MATERIALS AND METHODS: Blood was collected from DS (N=35; 7+/-3.8 years old) and their siblings (N=34; 10+/-4.5). Plasma Abeta40 and Abeta42, and neopterin levels were quantitated by sandwich ELISA. RESULTS: Abeta40 and Abeta42 levels were higher in DS than controls. The ratio of Abeta42/Abeta40 was lower in DS than in controls. There were significant negative correlations between age and Abeta40 in DS and controls, and between age and Abeta42 levels in DS but not in controls. There was no association of Abeta40 or Abeta42 levels with Apo E in either group. Neopterin levels were higher in DS than controls, and the levels were not correlated with Abeta40 and Abeta42 levels in DS or controls. CONCLUSIONS: The over expression of APP gene in DS leads to increases in plasma Abeta40 and Abeta42 levels before plaque formation in DS brain. Higher neopterin concentrations in DS reflect inflammatory cell activation. Further studies are needed to determine whether DS children with lower plasma Abeta42/Abeta40 ratios are at increased risk of developing AD during aging than those with higher ratios. PMID- 17275853 TI - A temperature-compensated model for circadian rhythms that can be entrained by temperature cycles. AB - From the viewpoint that reaction rates will change with temperature, we present a general method to build circadian clock models that generate circadian oscillations with almost constant period under different constant ambient temperature, and propose an algorithm estimating the parameter condition for compensated period against the change of temperature based on the PER single feedback loop model of Goldbeter [1995. A model for circadian oscillations in the Drosophila period protein (PER). Proc. R. Soc. London Ser. B 261, 319-324] for Drosophila. We show that the model with derived parameters can realize the temperature compensation over a wide range of temperature, and simultaneously can realize the entrainment to temperature cycles. PMID- 17275852 TI - Evolution of social learning does not explain the origin of human cumulative culture. AB - Because culture requires transmission of information between individuals, thinking about the origin of culture has mainly focused on the genetic evolution of abilities for social learning. Current theory considers how social learning affects the adaptiveness of a single cultural trait, yet human culture consists of the accumulation of very many traits. Here we introduce a new modeling strategy that tracks the adaptive value of many cultural traits, showing that genetic evolution favors only limited social learning owing to the accumulation of maladaptive as well as adaptive culture. We further show that culture can be adaptive, and refined social learning can evolve, if individuals can identify and discard maladaptive culture. This suggests that the evolution of such "adaptive filtering" mechanisms may have been crucial for the birth of human culture. PMID- 17275854 TI - Release of non-neuronal acetylcholine from the isolated human placenta is affected by antidepressants. AB - Non-neuronal acetylcholine (ACh) is released from the human placenta into the extracellular space via organic cation transporters (OCTs). The present experiments investigated whether ACh release from epithelial cells is affected by drugs which are substrates of OCTs. The antidepressant drugs amitriptyline and doxepine were tested as both substances are not approved for pregnant women but frequently used. Release of ACh was measured in 10 min intervals over a period of 100 min. Test substances were added from t=50 min of incubation onwards. The effect was calculated by comparing the ACh release of the last three samples (t=70-100 min; B2) with that immediately before the application of the test substances (t=20-50 min; B1). The baseline ACh release amounted to 2.07+/-0.17 nmol/10 min (n=29; villus). Under control conditions a B2/B1 ratio of 0.78+/-0.02 was obtained. The following B2/B1 ratios were found, when therapeutic drugs were added: 0.54+/-0.04 (n=7; P<0.05) in the presence of 10 microM amitriptyline; 0.44+/-0.04 (10; P<0.01) in the presence of 10 microM doxepin; 0.73+/-0.04 (13) in the presence of 10 microM metformin; 0.76+/-0.06 (7) in the presence of 10 microM minoxidil; 0.63+/-0.03 (10) in the presence of 1 microM theophylline. The results demonstrate that antidepressants reduce the release of non-neuronal ACh at least in the human placenta, most likely by intracellular substrate competition at the polyspecific organic cation transporters (OCTs) but only at concentrations roughly 30-fold above the therapeutic range. Theophylline may also interfere with the release of non-neuronal ACh. PMID- 17275855 TI - Detection of alpha7 nicotinic acetylcholine receptors with the aid of antibodies and toxins. AB - Neuronal nicotinic acetylcholine receptors (nAChRs) containing alpha7 subunit are well represented in the brain and some non-neuronal tissues, and their malfunctioning is associated with diverse pathologies. Therefore, detection and quantification of alpha7 nAChR are important tasks. The affinity-purified antibodies were prepared against the 1-23 and 179-190 fragments of the human and rat alpha7 nAChR extracellular domain. The specificity and selectivity of these alpha7 (1-23) and alpha7 (179-190) antibodies was tested by ELISA in model systems: the E. coli-expressed alpha7 subunit extracellular domain and the pituitary cell line GH(4)C(1) stably expressing human alpha7 nAChR. On the rat brain slices two antibodies and biotinylated alpha-cobratoxin specifically stained the hippocampus region known to be rich in alpha7 nAChR. Western blot analysis revealed that in the human thalamus membranes and in rat brain membranes, antibodies alpha7 (1-23) stained a single band of 62 kDa, while the alpha7 (179-190) antibodies stained a doublet of 53-54 kDa. The results obtained show that utilization of model systems and a combination of several antibodies with appropriately labeled toxins may provide better ways for detection of alpha7 nAChR. PMID- 17275856 TI - ACTX-8, a cytotoxic L-amino acid oxidase isolated from Agkistrodon acutus snake venom, induces apoptosis in Hela cervical cancer cells. AB - ACTX-8 is a protein isolated from Agkistrodon acutus snake venom in our laboratory. It demonstrates cytotoxic activity on various carcinoma cell lines in vitro. However, the mechanism by which ACTX-8 inhibits cell proliferation remains poorly understood. In this study the influence of ACTX-8 on the activation of apoptotic pathway in Hela cells was investigated. We demonstrated that cell death induced by ACTX-8 was concentration- and time-dependent. Apoptotic changes such as phosphatidyl serine externalization and DNA fragmentation were detected in ACTX-8-treated cells. Caspase activation and reactive oxygen species (ROS) production were involved in ACTX-8-induced apoptosis, but pan caspase inhibitor, z-VAD-fmk, could not inhibit cell death induced by ACTX-8 completely, which proved the existence of another pathway for ACTX-8-induced cell death. We found cytochrome c release into cytosol and mitochondrial membrane potential (MMP) dissipation in ACTX-8-treated cells, which indicated that mitochondrial pathway played a role in ACTX-8-induced cell apoptosis. The ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members was not changed by ACTX-8 treatment. However Bad and Bax were translocated from cytosol into mitochondria, and the coimmunoprecipitation result indicated that in mitochondria Bak and Bcl-xL dissociation was followed by the binding of Bad and Bcl-xL. Taken together, the study indicated mitochondrial pathway played an important role in the ACTX-8 induced apoptosis, which was regulated by Bcl-2 family members. PMID- 17275857 TI - Pharmacological characterization of receptor types mediating the dilator action of anandamide on blood vessels of the rat knee joint. AB - This study investigates the actions of N-(2-hydroxyethyl)-5Z,8Z,11Z,14Z eicosatetraenamide (anandamide) on blood flow of the rat knee joint. Topical bolus administration of anandamide (10-1000 nmol) onto the exposed knee joint capsules produced dose-dependent increases in the knee joint blood flow. Various antagonists were tested on the vasodilator response to 100 nmol anandamide. Capsazepine (N-[2-(4-chlorophenyl)ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2 benzazepine-2-carbothioamide), an antagonist of the transient receptor potential vanilloid type 1 (TRPV1) receptor, given at 10 and 100 nmol, suppressed the response by a maximum of 71%. A cannabinoid CB(1) receptor antagonist AM281 (10 nmol) and a CB(2) receptor antagonist AM630 (10 nmol) shortened its duration from 15 min to 5 min. O-1918 (1 nmol), an antagonist of the putative endothelial anandamide/abnormal-cannabidiol receptor, on its own or combined with capsazepine and the two cannabinoid receptor antagonists produced 38% and 24% inhibition on the peak vasodilator response to anandamide, respectively. URB597 (1 nmol), an inhibitor of fatty acid amide hydrolase (FAAH) suppressed the response by 40%, and an anandamide transporter inhibitor [N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z eicosatetraenamide] (AM404; 1 nmol) or a cyclo-oxygenase (COX) inhibitor flurbiprofen (20 nmol) abolished the response. These findings suggest the vasodilator action of anandamide in the rat knee joint involved hydrolysis of the compound by FAAH, production of COX-derived eicosanoid(s), activation of TRPV1 receptors, and a small component involved activation of endothelial anandamide/abnormal-cannabidiol receptors; a minor delayed dilator response was mediated by activation of conventional cannabinoid receptors. PMID- 17275858 TI - Cardiomyocyte apoptosis in the right auricle of patients with ostium secundum atrial septal defect diseases. AB - Ostium secundum atrial septal defect (osASD) is one of the most commonly occurring cardiac malformations. Although some embryological pathways have been elucidated, the molecular etiologies of ASD are not fully understood. Previous microarray analysis in our laboratory identified differentially expressed genes between osASD and normal right auricular myocardium. Of the 1056 differentially expressed genes, 14 genes were related to apoptosis: eight pro-apoptotic genes were up-regulated and six anti-apoptotic genes were down-regulated in ASD patients. In the current study, we utilized semi-quantitative RT-PCR, electron microscopy, TUNEL and flow cytometry to further understand the role of apoptosis in the atrium of osASD patients. RT-PCR results confirmed differential expression data from previous microarray studies. Additionally, while apoptosis was detected in the right auricular myocardium of all osASD patients, it was absent in controls. These data suggested apoptosis may play an important role in the pathogenesis of osASD or possibly occurs as a consequence of volume overload and hemodynamic changes in right atrium of osASD patients. PMID- 17275859 TI - A new Gompertz-type diffusion process with application to random growth. AB - Stochastic models describing growth kinetics are very important for predicting many biological phenomena. In this paper, a new Gompertz-type diffusion process is introduced, by means of which bounded sigmoidal growth patterns can be modeled by time-continuous variables. The main innovation of the process is that the bound can depend on the initial value, a situation that is not provided by the models considered to date. After building the model, a comprehensive study is presented, including its main characteristics and a simulation of sample paths. With the aim of applying this model to real-life situations, and given its possibilities in forecasting via the mean function, discrete sampling based inference is developed. The likelihood equations are not directly solvable, and because of difficulties that arise with the usual numerical methods employed to solve them, an iterative procedure is proposed. The possibilities of the new process are illustrated by means of an application to real data, concretely, to growth in rabbits. PMID- 17275860 TI - On the genesis of unilateral micrographia of the progressive type. AB - We report a patient who, following a focal ischemic lesion of the left basal ganglia, developed right hand micrographia characterised by progressive reduction of letter size during writing (progressive micrographia). The patient did not show relevant cognitive impairments, but achieved pathological scores in tests for verbal fluency, and cognitive flexibility and monitoring. A systematic investigation of the writing performances demonstrated that micrographia showed a clear length effect in whatever writing style or task, while it was not observed in drawing, or in left hand writing to a comparable extent. Right hand progressive micrographia was not affected by a concurrent motor and cognitive load; instead, switching between two kinds of allographic responses and presenting one letter at a time in copying tasks reduced severity of micrographia significantly. These findings support the view that progressive micrographia in our patient could be ascribed to a defect in regulating the motor output on the basis of self-generated strategies. This conclusion would be consistent with neuroimaging evidence about the role of the basal ganglia in the control of motor sequencing, and could suggest that progressive micrographia might be associated with specific executive defects. PMID- 17275861 TI - Photoperiodic regulation of behavioral responsiveness to proinflammatory cytokines. AB - Symptoms of bacterial infection include decreases in body mass (cachexia), induction of depressive-like hedonic tone (anhedonia), decreases in food intake (anorexia), and increases in body temperature (fever). Recognition of bacteria by the innate immune system triggers the release of proinflammatory cytokines which induce these sickness behaviors via actions at central and peripheral targets. In Siberian hamsters, exposure to short day lengths decreases both the production of proinflammatory cytokines and the magnitude of the symptoms of infection. Short day attenuation of sickness behaviors may arise solely from decreased production of cytokines; alternatively, substrates responsible for the generation of sickness behaviors may be less responsive to cytokines in short days. To discriminate among these hypotheses, Siberian hamsters were treated with either bacterial lipopolysaccharide (LPS; 25 microg) or recombinant mouse IL-1beta (rIL 1beta; 100 ng) following 11 weeks of exposure to long (15 h light/day) and short (9 h light/day) photoperiods. Replicating earlier work, the magnitude and/or duration of LPS-induced anorexia, anhedonia, cachexia, and fever were greater in long-day relative to short-day hamsters. A comparable short-day attenuation of sickness behaviors and fever was obtained in response to rIL-1beta treatment, despite treatment with identical concentrations of cytokine. These data suggest that hamsters subjected to immunoenhancing short days exhibit diminished symptoms of infection not solely because infections elicit lower levels of cytokine production, but also because the substrates upon which cytokines act become relatively refractory. PMID- 17275862 TI - 48-h glucose infusion in humans: effect on hormonal responses, hunger and food intake. AB - Experimentally-induced hyperglycemia by prolonged glucose infusion allows investigation of the effects of sustained stimulation of the pancreatic beta-cell on insulin secretion and sensitivity. Hormonal responses to a meal following prolonged glucose infusions have not been investigated. To determine if a 48-h glucose infusion alters hormonal responses to a test meal as well as food intake and hunger in normal weight individuals, 16 subjects (8 men, 8 women, age 18-30 years, mean BMI=21.7+/-1.6 kg/m2) were infused for 48 h with either saline (50 ml/h) or 15% glucose (200 mg/m2/min). Subjects ingested a 600 kcal mixed nutrient meal 3 h after infusion termination. Blood samples were taken during the 48 h and for 4 h following food ingestion. The 48-h glucose infusion elicited a metabolic profile of a glucose intolerant obese subjects, with increased plasma glucose, insulin and leptin (all P<0.01) and increased HOMA-IR (P<0.001). During meal ingestion, early insulin secretion was increased (P<0.05) but post-prandial glucose (P<0.01) and insulin (P<0.01) excursions were lower following the glucose infusion. Post-prandial plasma triglyceride concentrations were increased after glucose compared with saline. Food intake and hunger ratings were not different between the two conditions. Plasma leptin levels were inversely correlated with hunger (P<0.03) in both conditions and with food intake (P<0.003) during the glucose condition only. Thus, a 48-h glucose infusion does not impair post prandial hormonal responses, alter food intake or hunger in normal weight subjects. The glucose-induced increases in plasma leptin result in a stronger inverse relationship between plasma leptin and hunger as well as food intake. These data are the first to demonstrate a relationship between leptin and hunger in normal weight, non-calorically restricted human subjects. PMID- 17275864 TI - [Adenomatoid odontogenic tumor: two cases]. AB - INTRODUCTION: Adenomatoid odontogenic tumor, initially referred to as adenoameloblastoma, is a rare and benign odontogenic tumor. No recurrence has been reported after enucleation-resection. CASE REPORTS: We report two cases of adenomatoid odontogenic tumor, which illustrate the radiological and anatomic features of this tumor. They occurred in two 21 and 14 years-old teenagers who presented gingival swelling. The panoramic radiographs showed a radiolucent lesion with an impacted tooth. Enucleation-resection was performed with good outcome. DISCUSSION: The clinical, radiological and histological features of adenomatoid odontogenic tumor are distinct from those of ameloblastoma. It affects most commonly patients in the second decade of life predominantly females. This tumor is frequently misdiagnosed as other odontogenic cysts or tumors. We discuss the anatomoclinical features and the histogenesis of this rare tumor. PMID- 17275863 TI - [Primary mandibular tuberculosis]. AB - CASE REPORT: A 42 year-old patient presented a chronic submandibular tumefaction. Antibiotics were not effective. Diffuse osteolysis was noted on the panoramic. The diagnosis was provided by biopsy. The patient was cured after 9 months of antituberculosis tritherapy. DISCUSSION: Mandibular tuberculosis osteitis is extremely rare. Clinical and radiological presentation is not specific. Diagnosis can be suggested by the chronic course and the epidemiologic context. PMID- 17275866 TI - How patch configuration affects the impact of disturbances on metapopulation persistence. AB - Disturbances affect metapopulations directly through reductions in population size and indirectly through habitat modification. We consider how metapopulation persistence is affected by different disturbance regimes and the way in which disturbances spread, when metapopulations are compact or elongated, using a stochastic spatially explicit model which includes metapopulation and habitat dynamics. We discover that the risk of population extinction is larger for spatially aggregated disturbances than for spatially random disturbances. By changing the spatial configuration of the patches in the system--leading to different proportions of edge and interior patches--we demonstrate that the probability of metapopulation extinction is smaller when the metapopulation is more compact. Both of these results become more pronounced when colonization connectivity decreases. Our results have important management implication as edge patches, which are invariably considered to be less important, may play an important role as disturbance refugia. PMID- 17275867 TI - Long-term evolution of polygenic traits under frequency-dependent intraspecific competition. AB - We analytically investigate the long-term evolution of a continuously varying quantitative character in a diploid population that is determined additively by a finite number of loci. The trait is under a mixture of frequency-dependent disruptive selection induced by intraspecific competition and frequency independent stabilizing selection. Moreover, the trait is restricted to a finite range by constraints on the particular loci. Our investigations are based on explicit analytical results (provided by Burger [2005. A multilocus analysis of intraspecific competition and stabilizing selection on a quantitative trait. J. Math. Biol. 50, 355-396]; Schneider [2006. A multilocus-multiallele analysis of frequency-dependent selection induced by intraspecific competition. J. Math. Biol. 52, 483-523]) on the short-term dynamics under the assumption of linkage equilibrium. We show that the population always reaches a long-term equilibrium (LTE), i.e., an equilibrium that is resistant against perturbations of mutations of sufficiently small effect. In general, several LTEs can coexist. They can be calculated explicitly, and we provide necessary and sufficient conditions for their existence. In the case that more than one LTE exists, we exemplify numerically that the evolutionary outcome depends crucially on the initial genetic architecture, on the joint distribution of mutational effects across loci, and on the particular realization of the mutation process. Therefore, long term evolution cannot be predicted from the ecology alone. We further show that a partial order exists for the LTEs. The set of LTEs has a 'largest' element, an LTE which is reached during long-term evolution if the effects of the occurring mutant alleles are sufficiently large. PMID- 17275868 TI - Mitochondrial abnormalities--a link to idiosyncratic drug hepatotoxicity? AB - Idiosyncratic drug-induced liver injury (DILI) is a major clinical problem and poses a considerable challenge for drug development as an increasing number of successfully launched drugs or new potential drugs have been implicated in causing DILI in susceptible patient subsets. Although the incidence for a particular drug is very low (yet grossly underestimated), the outcome of DILI can be serious. Unfortunately, prediction has remained poor (both for patients at risk and for new chemical entities). The underlying mechanisms and the determinants of susceptibility have largely remained ill-defined. The aim of this review is to provide both clinical and experimental evidence for a major role of mitochondria both as a target of drugs causing idiosyncratic DILI and as mediators of delayed liver injury. We develop a unifying hypothesis that involves underlying genetic or acquired mitochondrial abnormalities as a major determinant of susceptibility for a number of drugs that target mitochondria and cause DILI. The mitochondrial hypothesis, implying gradually accumulating and initially silent mitochondrial injury in heteroplasmic cells which reaches a critical threshold and abruptly triggers liver injury, is consistent with the findings that typically idiosyncratic DILI is delayed (by weeks or months), that increasing age and female gender are risk factors and that these drugs are targeted to the liver and clearly exhibit a mitochondrial hazard in vitro and in vivo. New animal models (e.g., the Sod2(+/-) mouse) provide supporting evidence for this concept. However, genetic analyses of DILI patient samples are needed to ultimately provide the proof-of-concept. PMID- 17275869 TI - Characterization of Bizzy Nut extracts in estrogen-responsive MCF-7 breast cancer cells. AB - Kola acuminate, also known as Bizzy Nut or Kola Nut, is a natural product that contains bioactive chemicals that possess hormonal properties. The purpose of this study was to characterize the putative phytoestrogenic compounds present in Bizzy Nut for estrogenic-like activity. As an initial step, five extracts (E1 - hexane, E2 - ether, E3 - acetone, E4 - methanol and E5 - water) were sequentially generated using solid-liquid phase extraction and their bioactivity was examined in MCF-7, MDA-MB-468 and LNCaP cancer cell models. MTT cell viability, dye exclusion, caspase activity and microscopic assessment of apoptotic cells demonstrated that extracts of Bizzy were cytotoxic to MCF-7, MDA-MB 468 and LNCaP cells. In MCF-7 cells, the acetone extract (E3) at 100 ppm elicited a potent cytotoxic response with a growth-inhibitory concentration (GI(50)) of 67 ppm. In contrast, E3 stimulated growth in LNCaP cells. The ether extract (E2) showed a dose-dependent cytotoxic response with a GI(50) of 13 ppm in the LNCaP cell line. Examination of the apoptotic response induced by E2 and E3 paralleled the level of cell cytotoxicity observed in both cell lines. The methanol extract (E4) was the only extract that showed a time-, dose-, and estrogen-receptor-dependent stimulation of pS2 gene expression. On the other hand, the acetone extract (E3), which showed the highest degree of cytotoxicity, showed no transcription stimulation of pS2 in MCF-7 cells. Altogether, these data indicate that Bizzy contains unique active hormonal compounds that have specific biological properties that are cell line-dependent. PMID- 17275870 TI - Effects of microcystins on broccoli and mustard, and analysis of accumulated toxin by liquid chromatography-mass spectrometry. AB - Microcystins (MCs) are cyclic heptapeptides and protein phosphatase inhibitors produced by many species of cyanobacteria. MCs have been shown to cause adverse effects on animals as well as plants and therefore methods are needed for analysing MCs in different matrices. We assessed the effects of MC exposure on broccoli (Brassica oleracea var. italica) and mustard (Sinapis alba) by watering the seedlings with water containing 0, 1 or 10 microgMCsL(-1) (concentrations typically found in natural waters). Morphological characteristics, chlorophyll concentrations and chlorophyll fluorescence were investigated, but the only distinct difference compared to control plants was a slight (<10%) growth inhibition seen in broccoli. Afterwards the MC concentration of selected plant samples was quantitated using liquid chromatography-mass spectrometry. Among the four MC variants present in the exposure mixture, only MC-LR was clearly detectable, and the toxin was found only in the roots of broccoli and mustard. The detected MC-LR concentrations ranged from 0.9 to 2.6ng (g fresh weight)(-1). PMID- 17275871 TI - Reciprocal sequence exchange between non-retro viruses and hosts leading to the appearance of new host phenotypes. AB - Divergence among individuals of the same species may be linked to positional retrotransposition into different loci in different individuals. Here we add to recent reports indicating that individual variance occurs due to the integration of non-retroviral (potyviral) RNAs into the host genome via RNA recombination followed by retrotransposition. We report that in bees (Apis mellifera), approximately 30% of all tested populations carry a segment of a dicistrovirus in their genome and have thus become virus-resistant. Reciprocally, segments of host sequences have been found within defective-interfering-like sequences of a dicistrovirus. Similarly, host sequences were found fused to potyviral sequences, previously described integrated into their host genome. A potential, continuous RNA exchange leading to divergence is discussed. PMID- 17275872 TI - Relative dominance of epitope-specific CD8+ T cell responses in an F1 hybrid mouse model of respiratory syncytial virus infection. AB - CD8+ cytotoxic T lymphocytes are key effectors of adaptive immunity for the control of virus infections. Epitope-specific responses are hierarchical and the rules for dominance are not well defined. Here we show that the H2-Kd-restricted RSV M2(82-90) (KdM2(82-90)) epitope dominates the H2-Db-restricted RSV M187-195 (DbM187-195) epitope and influences epitope-specific effector function in the acute and memory phases of the immune response to primary RSV infection in H-2b/d hybrid mice. The hybrid mouse model provides a system to define rules of epitope hierarchy and better understand how antigen presentation and epitope competition affect the phenotype of effector and memory T cells. PMID- 17275873 TI - Destruction of EDTA by mediated electrochemical oxidation process: monitoring by continuous CO2 measurements. AB - The mediated electrochemical oxidation (MEO) process with cerium(IV) in nitric acid as the oxidizing medium was employed for the destruction of ethylenediaminetetraacetic acid (EDTA) in batch and continuous feeding modes. A complete mineralization of EDTA to CO(2) and water was achieved. The system parameters studied were the temperature (343, 353 and 368 K), concentration of nitric acid (2, 3 and 4M), Ce(IV) concentration (0.7-0.95 M), aqueous EDTA concentration (67-268 mM) , flow rate of EDTA addition (3.0-7.5 ml/min), and feeding time (30 min and 2h). The batch process CO(2) pattern clearly showed two distinct kinetic regimes. Accordingly the overall CO(2) formation rate constants were evaluated for fast and slow processes using pseudo first-order kinetics. In case of continuous organic feeding, the CO(2) formation rate constant was obtained using a new proposed mathematical procedure based on geometrical progression. The only parameter in the calculations was the first-order rate constant. The theoretical CO(2) evolution pattern was fitted on to the experimental data to obtain the formation rate constants. The activation energy was calculated based on the CO(2) formation constants and presented. The application of mathematical procedure predicted a steady-state attainment of CO(2) evolution for the destruction process during a long-term organic feeding and observed experimentally. PMID- 17275874 TI - Model-based evaluation of competition between polyphosphate- and glycogen accumulating organisms. AB - Many studies show that glycogen-accumulating non-polyphosphate organisms (GAOs) can compete with polyphosphate-accumulating organisms (PAOs) for organic substrate under anaerobic conditions and may indeed cause the deterioration of enhanced biological phosphorus removal (EBPR) systems. Understanding their behaviors in an anaerobic/aerobic (A/O) system at different operational conditions is essential in developing control strategies that ensure EBPR. A model-based evaluation of competition between PAOs and GAOs under different operational conditions was presented in this study. At 30 degrees C and a 10-day sludge age, the dominance of GAOs in the A/O sequencing batch reactor (SBR) was strongly dependent upon their considerable kinetic advantage in anaerobic acetate uptake. At 20 degrees C and a 10-day sludge age, the kinetic advantage of GAOs in anaerobic acetate uptake could be less, compared to that at 30 degrees C and a 10 day sludge age, leading to the relative dominance of PAOs and a stable phosphorus removal in the A/O system. At 30 degrees C and a 3-day sludge age, the parameters responsible for determining the aerobic distribution of anaerobically stored X(PHA) for both PAOs and GAOs, other than kinetic parameters of anaerobic acetate uptake, are important for them being dominant in the A/O SBR. In a situation when the q(PHA,P) value is lower than q(PHA,G) but comparable, PAOs may still be dominant in the A/O SBR, presumably because their aerobic conversion fraction of biomass production from PHA was higher than that of the GAOs. PMID- 17275875 TI - Heavy metal contaminants in Red Pandora (Pagellus erythrinus) tissues from the Eastern Aegean Sea, Turkey. AB - Heavy metal contents were investigated in different organ tissues of Red Pandora (Pagellus erythrinus) from the eastern Aegean Sea between May 1996 and July 1998. The concentrations of mercury in the muscle tissue ranged between 16 and 716, in liver 125-5451, in gonad 2.0-1858; cadmium in muscle nd-9.6, in liver 1.4-2245, in gonad nd-192; lead in muscle nd-1397, in liver 112-8311, in gonad nd-2927; zinc in muscle 1352-6693, in liver 2710-78705, in gonad 7273-168655; copper in muscle nd-383, in liver nd-21986, in gonad nd-20499 (microg/kg wet weight). The highest concentrations were generally found in the Southern Aegean Sea. All metal levels in muscle tissues are lower than the limits of European Dietary Standards and Guidelines. The metals ratios between liver and muscle indicated that the liver accumulated higher levels of metals than the muscle tissues. The bioaccumulation factor (BAFs) of metals was measured in muscle, liver and gonads. BAFs among the analysed elements showed the descending orders as Zn>Cu>Cd>Pb for muscle and gonads and Cd>Zn>Cu>Pb for liver. PMID- 17275876 TI - The effect of ozonation on natural organic matter removal by alum coagulation. AB - Natural organic matter (NOM) was extracted from a moderately colored, eutrophic surface water source (Forge Pond, Granby, MA), and fractionated into quasi homogeneous fractions. Fulvic acid (FA) and hydrophilic neutrals (HN) were the two most abundant NOM fractions that were isolated. Adsorption affinity of the isolated NOM fractions on preformed aluminum hydroxide flocs increased with increase in specific organic charge of the fractions, except for the two most highly charged fractions, FA and hydrophilic acids (HAA), which showed less adsorption affinity than expected based on their specific organic charge. Prior ozonation of FA and HN fractions resulted in a decline and an increase, respectively, in their adsorption affinity on aluminum hydroxide surface. Prior ozonation of Forge Pond raw water resulted in a progressive decline in dissolved organic carbon (DOC) removal by alum coagulation with increase in ozone dose. It appeared that ozone applied to raw water reacted preferentially with the humic fraction of NOM, resulting in the detrimental effects of ozonation on subsequent NOM removal by alum coagulation being magnified. Forge Pond raw water was pre coagulated to remove humic substances. Ozonation of the pre-coagulated water demonstrated the beneficial effects of ozonation on the removal of non-humic NOM through alum coagulation. A strategy for staged coagulation with intermediate ozonation was proposed for waters containing both humic and non-humic NOM for maximum DOC and specific UV absorbance at 254nm (SUVA) removal. PMID- 17275877 TI - Microorganisms in bioaerosol emissions from wastewater treatment plants during summer at a Mediterranean site. AB - Measurements were conducted at a Mediterranean site (latitude 35 degrees 31' north and longitude 24 degrees 03' east) during summer, to study the concentration of microorganisms emitted from a wastewater treatment plant under intensive solar radiation (520-840 W/m2) and at elevated air temperatures (25-31 degrees C). Air samples were taken with the Air Sampler MAS 100 (Merck) at each stage of an activated-sludge wastewater treatment (pretreatment, primary settling tanks, aeration tanks, secondary settling tanks, chlorination, and sludge processors). Cultivation methods based on the viable counts of mesophilic heterotrophic bacteria, as well as of indicator microorganisms of faecal contamination (total and faecal coliforms and enterococci), and fungi were performed. During air sampling, temperature, solar radiation, relative humidity and wind speed were measured. The highest concentrations of airborne microorganisms were observed at the aerated grit removal of wastewater at the pretreatment stage. A gradual decrease of bioaerosol emissions was observed during the advanced wastewater treatment from the pretreatment to the primary, secondary and tertiary treatment (97.4% decrease of mesophilic heterotrophic bacteria, and 100% decrease of total coliforms, faecal coliforms and enterococci), 95.8% decrease of fungi. The concentration of the airborne microorganisms at the secondary and tertiary treatment of the wastewater was lower than in the outdoor control. At the same time, the reduction of the microbial load at the waste sludge processors was 19.7% for the mesophilic heterotrophic bacteria, 99.4% for the total coliforms, and 100% for the faecal coliforms and the enterococci, 84.2% for the fungi. The current study concludes that the intensive solar radiation, together with high ambient temperatures, as well as optimal wastewater treatment are the most important factors for low numbers of microbes in the air. PMID- 17275878 TI - Stigmastane and hopanes as conserved biomarkers for estimating oil biodegradation in a former refinery plant-contaminated soil. AB - In the last decade, a refinery plant located in Lido Adriano, East Ravenna (Italy) has been subject to mineral oil contamination. The mineral crude oil, extracted from the offshore in Adriatic sea, consisted of 78% aliphatics, cyclic alkanes and saturated polycyclic hydrocarbons, 9% aromatics, polycyclic aromatic hydrocarbons (PAHs) and alkylated derivatives, and 13% of tars/asphaltenes. Analysis of soil after 10 years of natural attenuation revealed a complete depletion of linear (n-C(9)-C(24)), light aromatics (C1-C3/benzenes) and PAHs (C2/naphthalene, C1/phenanthrene); besides a substantial degradation of isoprenoids prystane and phytane, branched and cyclic alkanes. The remaining contaminants which withstood to natural degradation was saturated polycyclic hydrocarbons (perhydro-PAH derivatives), unsaturated polycyclic hydrocarbons (tetrahydro, dihydro-PAH derivatives), terpanes, steranes and unidentified compounds. Such residues resulted in 80% reduction of its concentration after two months of laboratory treatment. Samples were extracted by organic solvents, separated by silica/alumina gel column chromatography and analyzed by gas chromatography-mass selective detector (GC-MSD). Identification and quantification of aliphatic, cyclic alkanes, typical PAHs, terpanes and steranes were carried out to chromatograms of M/Z=85, 83, individual M/Zs, M/Z=191 and 217, respectively. The present work shows that, among numerous biomarkers present in the source oil, stigmastane and two isomers of hopane showed invariable concentrations after laboratory experiments that mimic natural biodegradation in the field, so they can be used as conserved internal biomarkers. These are very useful tools to assess alterations in less stable classes of saturated compounds contained in petroleum. Marked degradation of perhydro, tetrahydro, dihydro-PAH derivatives in the laboratory treatment has been evidenced. PMID- 17275879 TI - Physicochemical substance properties as indicators for unreliable exposure in microplate-based bioassays. AB - In the last years many efforts were made to transform standardized algal test protocols into low-cost microplate assays. While advantages were pointed out frequently, limitations are not systematically addressed, thus hindering a widespread utilisation. In this study a group of organic substances with a wide distribution of volatility (logKAW from -6.53 to -2.13) and lipophilicity (logKOW from 1.26 to 4.92) was investigated with respect to the influence of these physicochemical properties on their algal toxicity in different assays. Therefore the EC50 values were determined with a microplate assay based on ISO 8692 protocol and the results were compared with those of an established algal growth inhibition test conducted in air tight glass vessels. Using the ratio of the EC50 values, a clear connection between biological response and volatility as well as lipophilicity of test substances could be detected. Chemicals with a logKOW higher than 3 or a Henry coefficient logKAW higher than -4 were identified as less effective in the microplate assay than in the comparative assay. The loss in nominal concentration due to physicochemical properties could be shown to contribute to this using HPLC analysis. Consequently, when using microplate assay's one should be aware that lipophilic and volatile chemicals might be underestimated in their toxicity, which could be indicated from evaluating related physicochemical properties modelled from structural information prior to an experimental investigation. PMID- 17275880 TI - Identification of particles containing chromium and lead in road dust and soakaway sediment by electron probe microanalyser. AB - Individual particles containing Cr and/or Pb and other major components were identified in road dust from a heavily used road (hereinafter 'heavy traffic road dust'), road dust from a residential area and soakaway sediment by electron probe microanalyser to locate their sources and carrier particles. Individual particles containing high levels of Cr and/or Pb (>or=0.2%) were identified using wavelength dispersive spectrometry (WDS) map analysis. Chromium, Pb and other major elements were then determined by means of a combination of WDS and energy dispersive spectrometry in all identified particles, 50 particles containing neither Cr nor Pb from each type of road dust and soakaway sediment, and yellow road line markings. WDS map analysis revealed that many particles containing both Cr and Pb were present among the identified particles in heavy traffic road dust, whereas they were minor components in road dust from the residential area and soakaway sediment. The plots of X-ray intensities of Cr vs. Pb were linear for the identified particles containing both Cr and Pb in heavy traffic road dust, and the line closely fitted the plots for the three yellow road line marking samples. Individual particles were then classified using cluster analysis of element components. The results revealed that the adsorption of source materials or released metals onto soil minerals occurred in road dust and soakaway sediment, that the yellow road line markings were sources of Cr and Pb in heavy traffic road dust, and that materials containing Fe as a major component, such as stainless steel, were additional sources of Cr in both road dust and soakaway sediment. PMID- 17275881 TI - Algal bioaccumulation of triclocarban, triclosan, and methyl-triclosan in a North Texas wastewater treatment plant receiving stream. AB - Algae comprise the greatest abundance of plant biomass in aquatic environments and are a logical choice for aquatic toxicological studies, yet have been underutilized in this capacity. The lipid content of many algal species provides a point of entry for trophic transfer of lipophilic organic contaminants. Triclosan (TCS) and triclocarban (TCC), widely used antimicrobial agents found in numerous consumer products, are incompletely removed by wastewater treatment plant (WWTP) processing. Methyl-triclosan (M-TCS) is a metabolite of TCS more lipophilic than the parent compound. The focus of this study was to quantify algal bioaccumulation factors (BAFs) for TCS, M-TCS, and TCC in Pecan Creek, the receiving stream for the City of Denton, Texas WWTP. The complex algal compartment was field identified for collection and verified by laboratory microscopic description as being comprised of mostly filamentous algae (Cladophora spp.) and varying inconsequential levels of epiphytic diatoms and biofilm. Algae and water column samples were collected from the WWTP outfall, an upstream site, and two downstream sites and analysed by isotope dilution gas chromatography/mass spectrometry (GC/MS) for TCS and M-TCS and liquid chromatography/mass spectrometry (LC/MS) for TCC. TCS, M-TCS, and TCC in Pecan Creek water samples taken at and downstream from the WWTP were at low ppt concentrations of 50-200 ng l(-1) and were elevated to low ppb concentrations of 50-400 ng g(-1) fresh weight in algae collected from these stations. The resulting BAFs were approximately three orders of magnitude. TCS, M-TCS and TCC appear to be good candidate marker compounds for evaluation of environmental distribution of trace WWTP contaminants. Residue analysis of filamentous algal species typically occurring in receiving streams below WWTP discharges is a readily obtained indicator of the relative bioaccumulative potential of these trace contaminants. PMID- 17275882 TI - Survey of heavy metal pollution and assessment of agricultural soil in Yangzhong district, Jiangsu Province, China. AB - We investigated concentrations of Hg, Cd, Pb, Zn, Cu, As, Ni, and Cr in samples of soil, cereal, and vegetables from Yangzhong district, China. Compared to subsoils, the sampled topsoils are enriched in Hg, Cd, Cu, Pb, Zn, and As. High levels of Cd and Hg are observed in most agricultural soils. Concentrations of Cr and Ni show little spatial variation, and high Cu, Pb, and Zn contents correspond well to areas of urban development. High As contents are primarily recorded at the two ends of the sampled alluvion. The contents of Cd, Hg, and total organic carbon (TOC) increase gradually to maximum values in the upper parts of soil profiles, while Cr and Ni occur in low concentrations within sampled profiles. As, Pb, Cu, and Zn show patterns of slight enrichment within the surface layer. Compared to data obtained in 1990, Cd and Hg show increased concentrations in 2005; this is attributed to the long-term use of agrochemicals. Cr and Ni contents remained steady over this interval because they are derived from the weathering of parent material and subsequent pedogenesis. The measured As, Cu, Pb, and Zn contents show slight increases over time due to atmospheric deposition of material sourced from urban anthropogenic activity. Low concentrations of heavy metals are recorded in vegetables and cereals because the subalkaline environment of the soil limits their mobility. Although the heavy metal concentrations measured in this study do not pose a serious health risk, they do affect the quality of agricultural products. PMID- 17275883 TI - Size distribution and source identification of total suspended particulate matter and associated heavy metals in the urban atmosphere of Delhi. AB - A study of the atmospheric particulate size distribution of total suspended particulate matter (TSPM) and associated heavy metal concentrations has been carried out for the city of Delhi. Urban particles were collected using a five stage impactor at six sites in three different seasons, viz. winter, summer and monsoon in the year 2001. Five samples from each site in each season were collected. Each sample (filter paper) was extracted with a mixture of nitric acid, hydrochloric acid and hydrofluoric acid. The acid solutions of the samples were analysed in five-particle fractions by atomic absorption spectrometry (AAS). The impactor stage fractionation of particles shows that a major portion of TSPM concentration is in the form of PM0.7 (i.e. <0.7microm). Similarly, the most of the metal mass viz. Mn, Cr, Cd, Pb, Ni, and Fe are also concentrated in the PM0.7 mode. The only exceptions are size distributions pertaining to Cu and Ca. Though, Cu is more in PM0.7 mode, its presence in size intervals 5.4-1.6microm and 1.6 0.7microm is also significant, whilst in case of Ca there is no definite pattern in its distribution with size of particles. The average PM10.9 (i.e. <10.9microm) concentrations are approximately 90.2%+/-4.5%, 81.4%+/-1.4% and 86.4%+/-9.6% of TSPM for winter, summer and monsoon seasons, respectively. Source apportionment reveals that there are two sources of TSPM and PM10.9, while three and four sources were observed for PM1.6 (i.e. <1.6microm) and PM0.7, respectively. Results of regression analyses show definite correlations between PM10.9 and other fine size fractions, suggesting PM10.9 may adequately act as a surrogate for both PM1.6 and PM0.7, while PM1.6 may adequately act as a surrogate for PM0.7. PMID- 17275884 TI - Polychlorinated dibenzo-p-dioxins/furans and polychlorinated biphenyls in fresh fishes from Qiantangjiang River, China. AB - Muscles of two species of fish collected in Qiangtangjiang River were analyzed for polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). Average concentrations of total PCDD/Fs in Crucian carp and White Amur bream were 1.14-7.88 pg g(-1)ww and 1.02-8.18 pg g(-1)ww respectively. Corresponding values for PCBs were 469.36-10972 pg g(-1)ww and 364.79-4948.0 pg g(-1)ww. Average total WHO-TEQ of Crucian carp and White Amur bream from five areas ranged from 0.25 to 2.33 pg g(-1)ww and 0.30 to 1.70 pg g( 1)ww. The contamination level was compared with other studies and risk assessment was discussed. PMID- 17275885 TI - Age dependent acute oral toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and two anaerobic N-nitroso metabolites in deer mice (Peromyscus maniculatus). AB - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) transforms anaerobically into N nitroso compounds: hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and hexahydro-1,3,5 trinitroso-1,3,5-triazine (TNX). Exposure to these N-nitroso metabolites may occur in areas contaminated with explosives, as anaerobic degradation occurs via some bacteria and is one remediation strategy used for RDX. Few papers report acute oral toxicity and none have evaluated age dependent toxicity of RDX or its N-nitroso metabolites. Median lethal dose (LD50) was determined in deer mice (Peromyscus maniculatus) of three age classifications 21 d, 50 d, and 200 d for RDX, MNX, and TNX using the US EPA up-and-down procedure (UDP). Hexahydro-1,3,5 trinitro-1,3,5-triazine and N-nitroso metabolites caused similar overt signs of toxicity. Median lethal dose for 21 d deer mice were 136, 181, and 338 mg/kg for RDX, MNX, and TNX, respectively. Median lethal dose for 50 d deer mice were 319, 575, and 338 mg/kg for RDX, MNX, and TNX, respectively. Median lethal dose for 200 d deer mice were 158, 542, and 999 mg/kg for RDX, MNX, and TNX, respectively. These data suggest that RDX is the most potent compound tested, and age dependent toxicity may exist for all compounds and could play a role in RDX and RDX N nitroso metabolite ecological risk evaluation of terrestrial wildlife at RDX contaminated sites. PMID- 17275886 TI - Beneficial effects of dalteparin on haemostatic function and local tissue oxygenation in patients with diabetes, severe vascular disease and foot ulcers. AB - INTRODUCTION: A state of hypercoagulation and fibrinolytic dysfunction is present in individuals with diabetes, which may contribute to disturbed skin microcirculation and impaired ulcer healing. We have previously reported an improved outcome of chronic diabetic foot ulcers during treatment with dalteparin. In the present study we investigated the effects of dalteparin on skin microcirculation and haemostatic function. MATERIALS AND METHODS: 87 patients with diabetes, peripheral arterial obliterative disease and chronic foot ulcers were investigated in a prospective, randomised, double-blind and placebo controlled study. They were randomised to treatment with subcutaneous injections of 5000 U dalteparin (n=44) or placebo (n=43), once daily until ulcer healing or for a maximum of six months. Plasma fibrinogen, fibrin gel structure [permeability coefficient (Ks) and fiber mass/length ratio (mu)], prothrombin fragment 1+2 (F1+2) antigen, plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator (tPA) antigen were analysed before randomization (baseline value), and at the end of the treatment period. The skin microcirculation of the foot was investigated by transcutaneous oxygen tension (TcPO(2)) and laser Doppler fluxmetry (LDF). RESULTS: The changes (Delta-values) of Ks, mu, tPA and TcPO(2) were higher (p<0.05) during treatment with dalteparin, as compared to the changes during treatment with placebo. At baseline, plasma fibrinogen and Ks were significantly correlated to TcPO(2). CONCLUSIONS: Local skin oxygenation improved and a less thrombogenic fibrin gel structure was formed in patients treated with dalteparin. Beneficial effects on haemostatic function are likely to contribute to the improved skin oxygenation observed during treatment with dalteparin. PMID- 17275888 TI - Induction of apoptosis and inhibition of telomerase activity by arsenic trioxide (As2O3) in endometrial carcinoma cells. AB - OBJECTIVES: To examine the effects of arsenic trioxide (As2O3) on human endometrial carcinoma cell lines with respect to cytotoxicity and the induction of apoptosis and telomerase expression in vitro. METHODS: Four endometrial carcinoma cell lines (Ishikawa, ECC-1, RL-95-2 and Hec-1B) were treated with increasing concentrations of As2O3. RESULTS: As2O3 inhibited proliferation of all cell lines in a concentration and time-dependent manner (IC50 range of 3-7 microM). Coincident with the inhibition of growth, As2O3 also induced apoptosis in all cell lines as measured by the time-dependent increase in M30 antibody fluorescence (binds a caspase-cleaved epitope of cytokeratin 18) detected by flow cytometry, and reduced telomerase activity by decreasing the hTERT mRNA expression. CONCLUSION: As2O3 may exert anti-tumor effects through the induction of the apoptosis pathway and telomerase and hTERT may play an important role in the anti-apoptotic effects which are observed when endometrial cancer cells are treated in vitro with As2O3. PMID- 17275887 TI - Thrombin-thrombomodulin inhibits prourokinase-mediated pleural mesothelial cell dependent fibrinolysis. AB - Fibrin deposition is a hallmark of pleural inflammation and loculation but understanding of mechanisms by which mesothelial cells regulate intrapleural fibrinolysins remains incomplete. We speculated that pleural mesothelial cells regulate local fibrinolytic capacity via processing of single chain urokinase type plasminogen activator (scuPA). Pretreatment of human pleural mesothelial (MeT-5A) cells with TGF-beta or thrombin, either alone or in combination, inhibited urokinase (uPA)-mediated fibrinolysis by MeT-5A. Thrombin, unlike TGF beta, inhibited fibrinolysis without induction of PAI-1, suggesting that thrombin mediated cleavage of scuPA inhibits the fibrinolytic capacity of MeT-5A cells. Thrombin cleaves both purified scuPA as well as that secreted by MeT-5A cells and cell surface thrombomodulin accelerates thrombin-mediated cleavage of scuPA to inhibit cellular fibrinolytic activity. Molecular dynamics analyses demonstrated that thrombin-cleaved scuPA (uPAt) do not acquire a catalytically active conformation and that secondary plasminogen binding sites of uPA implicated in plasminogen activation are distorted in uPAt, explaining, at least in part, why uPAt is a poor enzyme. uPAt was detectable in transudative and exudative pleural effusions from patients. Intrapleural administration of scuPA generated increased levels of uPAt in PF of rabbits with pleural injury and loculation induced by tetracycline in vivo. This pathway is operative in diverse forms of pleural injury, restricts the urokinase-dependent fibrinolytic capacity of pleural mesothelial cells and contributes to local control of fibrinolytic activity via processing of endogenous or exogenous scuPA within the pleural compartment. PMID- 17275889 TI - Which clinical/pathologic factors matter in the era of chemoradiation as treatment for locally advanced cervical carcinoma? Analysis of two Gynecologic Oncology Group (GOG) trials. AB - PURPOSE: To explore clinical/pathologic factors associated with prognosis of patients with locally advanced cervical carcinoma treated with weekly cisplatin and pelvic radiation. METHODS: We retrospectively reviewed data from 335 women who received weekly cisplatin and radiation while participating in similar arms of two GOG studies (protocols 120 and 165). Progression-free survival (PFS) and overall survival (OS) were evaluated for associations between clinical/pathologic factors and prognosis. Prognosis and selected toxicities were also compared between studies. RESULTS: Four-year PFS and OS for stage II patients were 64.2% and 68.1%, respectively for those treated on GOG 120 and 65.8% and 73.9% for those treated on GOG 165, compared to 51.4% and 55.4% for stage III/IV patients respectively treated on GOG 120 and 37.7% and 42.7% respectively for those treated on GOG 165. In multivariate analysis, stage, tumor grade, race and age were independently predictive of PFS and OS (for all, p<0.05). Prolonged (delayed for any cause) radiation was associated with poorer PFS (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.16-3.38; p=0.012) and OS (HR, 1.88; 95% CI, 1.08 3.26; p=0.024) in GOG 165 but not GOG 120. CONCLUSIONS: FIGO stage, tumor grade, race and age are prognostic in patients with locally advanced cervical carcinoma treated with concurrent cisplatin and radiation. This exploratory analysis has generated a hypothesis that clinical staging (as per GOG 165) is less sensitive in detecting aortic nodal metastases compared to surgical staging (as per GOG 120) and may be associated with poorer prognosis particularly when radiation is prolonged. Prospective clinical studies are needed to test this hypothesis. PMID- 17275890 TI - HPV status in sentinel nodes might be a prognostic factor in cervical cancer. AB - OBJECTIVE: Although there have been studies that focused on the correlation between the HPV presence of pelvic lymph nodes and pathological metastasis in patients with cervical cancer, the biologic role of HPV DNA in lymph nodes still remains uncertain. We performed this study to investigate the correlation between the sentinel-node HPV status and pelvic lymph node metastasis in patients with cervical cancer. The patients were followed up for 3 years to evaluate the clinical role of HPV in sentinel nodes as a prognostic factor. METHODS: From August 2001 to July 2003, 57 patients affected by stages IB-IIA cervical cancer had sentinel-node biopsies performed during radical hysterectomy and pelvic and paraaortic lymphadenectomy. Each detected sentinel node was divided into two parts. One part of them was submitted for frozen section examination and the other was submitted for HPV typing by oligonucleotide microarray. After follow up, we analyzed the outcome of the patients with respect to the influence of sentinel-node HPV. RESULTS: Sentinel nodes were identified in all patients. A total of 79 nodes from 57 patients were detected as sentinel nodes. Metastasis in the sentinel nodes were found in 10 patients (17.6%) by frozen section and 11 patients by pathologic examination. The results of sentinel lymph node frozen biopsy were statistically significant for predicting the metastasis of the pelvic lymph nodes (P<0.05), but showed one false-negative case. HPV DNA was detected in the cervical cancer lesions of 55 patients (96.5%) and 80.0% (44/55) of them were found to have HPV DNA in the sentinel nodes as well. HPV DNA was detected in sentinel nodes of 10 patients among 11 patients with lymph node metastasis. Disease recurred in five patients and one of them did not show pelvic lymph node metastasis at surgery. But, all of these patients had HPV in sentinel nodes. The combination of sentinel-node frozen biopsy and HPV typing showed a negative predictive value of 100% in predicting non-metastasis of lymph node and no recurrence of disease. CONCLUSION: Our results suggested the possibility that sentinel-node HPV typing could play a supportive role to reduce the false negative rate of the sentinel-node biopsy. All of five patients with recurrence had HPV infection in the sentinel nodes. Absence of HPV in sentinel nodes showed reliable negative predictive value for lymph node metastasis and recurrence. Additional study will be needed to confirm the clinical application of the sentinel-node procedure and to determine whether there is a correlation of HPV status of sentinel nodes to lymph node metastasis and recurrence in cervical cancer patients. PMID- 17275891 TI - The influence of n-6 fatty acid supplemented diet on the effect of imipramine in an animal model of depression. AB - Recent data have shown an association between polyunsaturated fatty acid and depression. This study examined the effect of the supplementation with n-6 fatty acid on the behavior of rats treated with imipramine and submitted to the Forced Swimming Test (FST). Non-supplemented imipramine-treated rats presented a significant reduction of immobility time in the FST whereas n-6 fatty acid supplemented rats showed a significantly higher immobility time. Imipramine significantly increased norepinephrine plasma concentrations in the two groups. These results show that the diet supplemented with n-6 fatty acid altered the behavior of the animals in the FST, inhibiting the imipramine effect. PMID- 17275892 TI - Participation of dihydrostyryl-2-pyrones and styryl-2-pyrones in the central effects of Polygala sabulosa (Polygalaceae), a folk medicine topical anesthetic. AB - This study was undertaken to evaluate the psychopharmacological effects in mice of the hydroethanolic extract (HE), aqueous, hexane and ethyl acetate (EA) fractions, and 6-methoxy-7-prenyloxycoumarin, three dihydrostyryl-2-pyrones and three styryl-2-pyrones isolated from Polygala sabulosa (Polygalaceae), a folk medicine used as a topical anesthetic. In the elevated plus-maze test (EPM), the HE of P. sabulosa and its EA induced an increase in the percentage of time spent on, and in the frequency of entries into the open arms, as well as in the number of unprotected head-dipping, besides a reduction in protected stretch-attend postures, thus indicating an anxiolytic-like profile of action for this plant species. In the hypnosis test, HE and EA enhanced the duration of pentobarbital induced sleep, a hypnosedative effect confirmed in ethyl ether-induced hypnosis. Moreover, both preparations reduced the duration of the first convulsion induced by pentylenetetrazol, besides decreasing the severity of the seizures. The dihydrostyryl-2-pyrones (1) and (3) as well as styryl-2-pyrones (4) and (7), centrally administered, showed a similar anxiolytic-like effect in the EPM test, while the dihydrostyryl-2-pyrone (2) and styryl-2-pyrone (5) were inactive at the doses used here. These results suggest that P. sabulosa is a herbal medicine which possesses anxiolytic-like, hypnosedative and anticonvulsant effects, and these central effects can be attributed to the presence of the dihydrostyryl-2 pyrone and styryl-2-pyrone compounds. PMID- 17275893 TI - Repeated cannabinoid administration increases indices of noradrenergic activity in rats. AB - The present study examined the impact of repeated administration of a synthetic cannabinoid agonist, WIN 55,212-2 on the coeruleo-cortical pathway, a circuit implicated in anxiety. Male Sprague-Dawley rats received repeated systemic injections of WIN 55,212-2 (3.0 mg/kg). A separate group of rats received repeated WIN 55,212-2 injections followed by a period of abstinence. Control animals received vehicle injections. Ninety minutes following the last injection on day 8, anxiety-related behavior was assessed using the elevated plus maze. The abstinent group was tested after another 8 days. Following behavioral testing, brain tissue was extracted from the locus coeruleus (LC) and probed for tyrosine hydroxylase (TH) expression. In a separate group of animals, in vivo microdialysis was used to monitor extracellular norepinephrine efflux in the frontal cortex following repeated WIN 55,212-2 administration and following a period of abstinence. Repeated administration of WIN 55,212-2 evoked an anxiogenic-like response that was accompanied by an increase in TH protein expression in the LC. A similar neurochemical profile was observed using in vivo microdialysis where an augmented increase in cortical norepinephrine efflux was identified in response to a systemic injection of WIN 55,212-2 on day 8. Anxiety like behavior, catecholamine synthesizing enzyme levels and NE efflux returned to control values after 8 days of abstinence. The present findings indicate that repeated administration of a synthetic cannabinoid receptor agonist induces transient anxiety-like behaviors that correlate with increases in catecholamine synthesizing enzyme expression in the LC and augmented norepinephrine efflux in response to a challenge injection of WIN 55,212-2. PMID- 17275894 TI - Sex differences in (+)-amphetamine- and (+)-methamphetamine-induced behavioral response in male and female Sprague-Dawley rats. AB - (+)-Methamphetamine (METH) and (+)-amphetamine (AMP) are structurally similar drugs that are reported to induce similar pharmacological effects in rats of the same sex. Because pharmacokinetic data suggest female rats should be more affected than males, the current studies sought to test the hypothesis that the behavioral and temporal actions of METH and AMP should be greater in female Sprague-Dawley rats than in males. Using a dosing regimen designed to reduce the possibility of tolerance and sensitization, rats were administered 1.0 and 3.0 mg/kg intravenous drug doses. Distance traveled, rearing events and focal stereotypies (e.g., head weaving, sniffing) were measured. Female rats traveled significantly greater distances and displayed a greater number of rearing events than males after both doses. Analysis of stereotypy ratings after 3.0 mg/kg revealed that focal stereotypies were more pronounced and lasted longer in females. The second study compared the potencies of METH and AMP in inducing locomotor activity and focal stereotypies in each sex. No differences in potency were found when METH and AMP effects were compared within males or females. In summary, these studies showed female rats displayed greater and longer-lasting locomotor activity and more stereotypic behaviors, supporting earlier evidence of significant sexual dimorphism in pharmacokinetics. PMID- 17275896 TI - The effect of walking on fitness, fatness and resting blood pressure: a meta analysis of randomised, controlled trials. AB - OBJECTIVE: The purpose of this review was to perform a meta-analysis on walking intervention studies in order to quantify the magnitude and direction of walking induced changes that may alter selected cardiovascular risk factors. METHOD: Twenty-four randomised controlled trials of walking were assessed for quality on a three-point scale. Data from these studies were pooled and treatment effects (TEs) were calculated for six traditional cardiovascular risk variables: body weight, body mass index (BMI), percentage body fat, aerobic fitness (V(O(2) )max in ml kg(-1) min(-1)) and resting systolic and diastolic blood pressure. Weighted TEs were analysed using a random effects model with weights obtained using the inverse of the individual TE variances. Random effects models were used to investigate the influence of both study quality and exercise volume (<150 vs. > or =150 min week(-1)). RESULTS: Random effects modelling showed that walking interventions increased V(O(2) )max and decreased body weight, BMI, percent body fat and resting diastolic blood pressure in previously sedentary adults (p<0.05 for all). CONCLUSION: The results of this study provide evidence that healthy but sedentary individuals who take up a programme of regular brisk walking improves several known risk factors for cardiovascular disease. PMID- 17275895 TI - Willingness to participate in HIV vaccine trials: the impact of trial attributes. AB - OBJECTIVES: To assess willingness to participate (WTP) in hypothetical Phase III preventive HIV vaccine trials, and the impact of trial attributes on WTP, among low socioeconomic, ethnically diverse adults from communities at elevated risk for HIV infection. METHOD: Participants (n=123; median age=38; 69% male; 37% Latino; 14% African-American) were recruited in Los Angeles in 2003 using multi site, venue-based sampling. WTP was assessed for eight hypothetical HIV vaccine trials that varied across seven dichotomous attributes, using a 2(7-4) fractional factorial experimental design. Individual-specific impact of vaccine trial attributes on WTP was estimated using within-individual ANOVA and then meta analyzed across individuals. RESULTS: Mean WTP for eight hypothetical vaccine trials ranged from 1.74 to 3.81 (1=highly unlikely, 5=highly likely). Lower WTP was associated with vaccine-induced infection risk (impact=0.88, p<0.0001), false HIV-positives (0.53, p<0.0001), no provision of free HIV medications (0.52, p<0.0001), and longer trial duration (0.27; p=0.0002). CONCLUSION: HIV vaccine trial attributes may strongly influence WTP. Although existing candidate vaccines cannot cause HIV infection, perceptions of risk may impede WTP. Eliciting trial preferences and concerns prior to trial implementation may enable accommodation of participant preferences and support tailored interventions to address concerns and misconceptions to facilitate enrollment in safe and ethical trials among vulnerable communities. PMID- 17275897 TI - Associations of androgens with physical activity and fitness in young black and white men: the CARDIA Male Hormone Study. AB - OBJECTIVE: The association between physical activity or cardiovascular fitness and chronic disease risk in men might be mediated, in part, through androgens. Limited data exists on the potential associations of activity or fitness with serum hormones. We examined the associations of serum testosterone and sex hormone binding globulin (SHBG) concentrations with physical activity and cardiorespiratory fitness in black and white young men. METHOD: Data were collected from 391 black and 604 white male participants of the Coronary Artery Risk Development in (Young) Adults (CARDIA) Male Hormone Study aged 24-32 in 1992 1993. Cross-sectional associations of serum total testosterone (TT), bioavailable testosterone (BT) and SHBG levels with self-reported total physical activity score, and in a subset of men (n=617) with cardiorespiratory fitness measured via duration on a treadmill test were assessed. Five-year longitudinal associations of change in hormones with changes in physical activity also were examined. RESULTS: There were no cross-sectional or longitudinal associations of physical activity with SHBG, TT or BT in either black or white men. Fitness was positively associated with SHBG only in white men, but was not associated with TT or BT in either group. CONCLUSION: Overall the results do not support an association of self-reported physical activity with androgens, whereas they do suggest that fitness might be associated with SHBG in white men. PMID- 17275899 TI - Pedometer determined physical activity levels in primary school children from central England. AB - OBJECTIVE: To assess ambulatory physical activity in school children from central England, to examine any variation in activity between weekdays and weekends and to determine the percentage of children meeting recently identified cut-off steps/day for health. METHOD: 208 British primary school children (101 boys and 107 girls, mean age 9.3+/-0.9 years) from central England wore a sealed pedometer for 4 consecutive days (2 weekend and 2 weekdays) during 2006 from which daily step counts were determined. Data were collected over winter, spring and summer terms. Repeated measures analysis of variance was used to examine potential time (weekend versus weekday), gender and age differences in steps/day. RESULTS: Children attained significantly higher mean steps/day during weekdays than weekends (p<0.001), and boys attained significantly higher mean steps/day than girls (p<0.05). Mean steps/day values were 13,827 (38,201) and 10,334 (4436) for weekdays and weekends and 12,263 (3789) and 11,748 (3310) for boys and girls respectively. 28.7% of boys and 46.7% of girls met or exceeded the BMI referenced cut-offs for health. CONCLUSION: Physical activity was greater during weekdays compared to weekends and boys were more active than girls but the majority of children did not meet the health-related cut-off points. PMID- 17275900 TI - An update on the use of B-mode ultrasonography in female pig reproduction. AB - After technological advances allowed for the adaptation of B-mode ultrasonography equipment for use in pig facilities, ultrasonography quickly established itself as an ideal diagnostic aid for determining pregnancy status in pigs. In recent years, B-mode ultrasonography has found increased application in its use for monitoring ovarian activity and in estimating time of ovulation in pigs. B-mode ultrasonography is also valuable in providing a detailed assessment of the sow's ovaries and uterus to determine if pathological conditions exist, which could be contributing to poor individual or herd reproductive performance. In its most recent application in pigs, the gilt genital tract has been characterized peripubertally by ultrasonography in order to detect onset of puberty. The purpose of this review is to provide an update on the current status of B-mode ultrasonography in pig reproduction, and how this technology can be of value when used in pig production medicine. PMID- 17275898 TI - Non-alcoholic beverage and caffeine consumption and mortality: the Leisure World Cohort Study. AB - OBJECTIVE: To examine the effects of non-alcoholic beverage and caffeine consumption on all-cause mortality in older adults. METHODS: The Leisure World Cohort Study is a prospective study of residents of a California retirement community. A baseline postal health survey included details on coffee, tea, milk, soft drink, and chocolate consumption. Participants were followed for 23 years (1981-2004). Risk ratios (RRs) of death were calculated using Cox regression for 8644 women and 4980 men (median age at entry, 74 years) and adjusted for age, gender, and multiple potential confounders. RESULTS: Caffeine consumption exhibited a U-shaped mortality curve. Moderate caffeine consumers had a significantly reduced risk of death (multivariable-adjusted RR=0.94, 95% CI: 0.89, 0.99 for 100-199 mg/day and RR=0.90, 95% CI: 0.85, 0.94 for 200-399 mg/day compared with those consuming <50 mg/day). Individuals who drank more than 1 can/week of artificially sweetened (but not sugar-sweetened) soft drink (cola and other) had an 8% increased risk (95% CI: 1.01-1.16). Neither milk nor tea had a significant effect on mortality after multivariable adjustment. CONCLUSIONS: Moderate caffeine consumption appeared beneficial in reducing risk of death. Attenuation in the observed associations between mortality and intake of tea and milk with adjustment for potential confounders suggests that such consumption identifies those with other mortality-associated lifestyle and health risks. The increased death risk with consumption of artificially sweetened, but not sugar sweetened, soft drinks suggests an effect of the sweetener rather than other components of the soft drinks, although residual confounding remains a possibility. PMID- 17275901 TI - In vitro maturation and early developmental capacity of bovine oocytes cultured in pure follicular fluid and supplementation with follicular wall. AB - Mammalian oocytes mature in follicular fluid (FF), surrounded by follicular cells. In the present study, in vitro maturation of bovine oocytes cultured in FF from dominant follicles 15-17mm in diameter (with various forms of heat pretreatment) and supplementation with follicular wall from follicles 3-5mm in diameter (FW1) were examined. Heat pretreatment of FF was as follows: (1) no treatment (FF1); (2) 56 degrees C for 30min (FF2); and (3) 100 degrees C for 20s (FF3). After IVM in FF1, oocytes underwent IVF and IVC and embryo development was assessed (up to the morula stage). The rate of oocyte maturation was decreased in pure FF1 versus control (44.5% versus 62.8%, P<0.001). In the control medium, FW1 did not significantly affect nuclear maturation. By contrast, the addition of FW1 to FF1 increased the rate of matured oocytes approximately two-fold (85.9% versus 45.6%, P<0.001). Furthermore, the maturation rate in the FF+FW1 system declined (from 85.9 to 71.0%, P<0.001), whereas that in the FF system increased (from 45.6 to 71.6%, P<0.001) with increased temperature of the FF treatment. Supplementation of the control medium with FW1 increased the yield of morulae (42.6% versus 13.7%, P<0.001). However, the stimulatory effect of FW1 on the morula rate was much higher in pure FF1 (72.5% versus 31.7%, P<0.001). These findings indicated, for the first time, the stimulatory impact of FW1 on in vitro maturation and early developmental capacity of bovine oocytes cultured in pure FF from dominant follicles. We also inferred that bovine FF constituents affecting bovine oocyte maturation and the meiosis-promoting ability of the FW were heat labile. PMID- 17275902 TI - The effects of self-disclosure and non self-disclosure of stuttering on listeners' perceptions of a person who stutters. AB - The aim of this study was to examine listener perceptions of an adult male person who stutters (PWS) who did or did not disclose his stuttering. Ninety adults who do not stutter individually viewed one of three videotaped monologues produced by a male speaker with severe stuttering. In one monologue, 30 listeners heard the speaker disclose stuttering at the beginning and in another monologue, 30 listeners heard the speaker disclose stuttering at the end. A third group of 30 listeners viewed a monologue where no disclosure of stuttering occurred. After listeners viewed a monologue, they were asked to rate a set of six Likert scale statements and answer three open-ended questions. The results showed that only one of six Likert statements was significantly different across the three conditions. The only statement that was different was that the speaker was perceived to be significantly more friendly when disclosing stuttering at the end of the monologue than when not disclosing stuttering. There were no significant differences between the percentage of positive and negative comments made by listeners across the three conditions. Listeners' comments to each open-ended question showed they were comfortable listening to stuttering with or without disclosure and slightly more than half of the listeners believed their perceptions of the speaker did not change when he disclosed stuttering. The results also showed that the speaker who disclosed stuttering at the beginning of the monologue received significantly more positive listener comments than when he disclosed stuttering at the end of the monologue. Results are discussed relative to comparisons with the study, the clinical relevance of acknowledging stuttering as a component of treatment, and future research on the self-disclosure of stuttering. EDUCATIONAL OBJECTIVES: The reader will be able to: (1) describe how different groups of listeners perceive and respond to two conditions of self disclosure of stuttering and one condition involving non self-disclosure of stuttering; (2) summarize the range of listener responses to and benefits of self disclosure of stuttering; and (3) describe the value of self-disclosure of stuttering for the listener and the speaker. PMID- 17275904 TI - Hyperbaric oxygen: a potential new therapy for leukemia? PMID- 17275903 TI - Hypoxia and lactate production in trophoblast cells. AB - The etiology of preeclampsia is unknown but is thought to be related to hypoxia in the placenta. We previously reported that the enzyme lactate dehydrogenase (LDH) has increased activity and gene expression in placentas from preeclamptic pregnancies [Tsoi SCM, Zheng J, Xu F, Kay HH. Differential expression of lactate dehydrogenase isozymes (LDH) in human placenta with high expression of LDH-A(4) isozyme in the endothelial cells of pre-eclampsia villi. Placenta 2001;22:317 22]. LDH is responsible for pyruvate conversion to lactate through glycolysis. In this study, we further investigated the role of hypoxia in primary trophoblast cells and a cultured cell line, JEG3 cells, to obtain a better understanding of how it affects the activities of lactate dehydrogenase, lactate production and regulatory genes, as a possible model for preeclampsia. Primary trophoblast cells and JEG3 cells were cultured under 1% oxygen. At 6, 12 and 24h, cells were analyzed for LDHA and LDHB isozyme activities, mRNA and protein expression compared to standard culture conditions. Lactate was measured from cell medium. The hypoxia inducible transcription factor (HIF-1alpha) protein expression was confirmed by western blot. Two lactate transporters (MCT1 and MCT4) mRNA and protein expression were also studied under hypoxia. Finally, lactate was measured in plasma obtained from patients with severe preeclampsia. Under hypoxic conditions, LDHA mRNA is increased in primary trophoblast cells and JEG3 cells. The HIF-1alpha protein expression is higher in hypoxia-treated JEG3 cells than control. LDHA isozyme activity and its protein expression are increased most significantly at 24h of culture under hypoxia. However, LDHB protein is unchanged while its mRNA is decreased. Lactate secretion from JEG3 cells under hypoxia is increased, as is the lactate levels in the plasma from preeclampsia patients. Of the two lactate transporters studied, MCT4 mRNA and protein level are increased under hypoxia. Our findings support the role of hypoxia in inducing HIF-1alpha activity in trophoblasts and increasing LDH transcription as well as its activity. Higher levels of lactate are produced and secreted which may contribute to the higher lactate levels in plasma of preeclamptic patients. These mechanisms may be important in the pathophysiology of preeclampsia. PMID- 17275905 TI - Cloning and characterizing of the ovine MX1 gene promoter/enhancer region. AB - Ovine MX1 (MX1) is expressed in the uterus during the estrous cycle and is strongly up-regulated during early pregnancy in the uterus and peripheral blood leukocytes. In this study we cloned the MX1 gene promoter/enhancer, and tested its response to interferon tau (IFN-tau). To address the role of IFN tau in regulating MX1 expression, serial deletion mutants were prepared along with a clone that contained a full-length promoter including the two proximal ISREs but lacking an intronic ISRE site. Promoter deletions showed the two proximal ISRE sites, but not the intronic ISRE site, were required for maximal response to IFN tau. Interestingly, MX1 promoter deletion mutants revealed the presence of distal positive (-920 to -715) and negative (-715 to -437) regulatory regions. Identifying positive and negative regulatory regions in MX1 promoter will help define the complex regulation of MX1 during early pregnancy in ruminants. PMID- 17275906 TI - Isolation and characterization of a new plasmid pSpnP1 from a multidrug-resistant clone of Streptococcus pneumoniae. AB - A novel Streptococcus pneumoniae plasmid (pSpnP1; 5413bp) has been isolated from the multidrug-resistant clone Poland(23F)-16, and its complete nucleotide sequence has been determined. Sequence analysis predicted seven co-directional open reading frames and comparative analyses revealed that plasmid pSpnP1 is different to pDP1, the only previously described pneumococcal plasmid, whereas it is highly similar to pSt08, a plasmid from Streptococcus thermophilus. A double stranded origin for replication similar to the replication origin of the pC194/pUB110 family was located upstream of the putative rep gene (orf2). It also contained a 144-bp region with over 60% identity to the single-stranded origin type A of the Streptococcus agalactiae plasmid pMV158/pLS1. Detection of single stranded DNA by Southern blot analysis indicated that pSpnP1 replicates via a rolling circle mechanism. Interestingly, the product of orf1 has a putative Zonular occludens toxin conserved domain present in toxigenic strains of Vibrio cholerae. Real-time PCR assays revealed that this ORF was expressed. Hybridization experiments showed that the pSpnP1 replicon was unusual among other examined antibiotic-resistant pneumococcal clones, although the recombinant plasmids based on pSpnP1 were able to replicate in Bacillus subtilis and Lactococcus lactis. PMID- 17275907 TI - Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteins. AB - Lectins are proteins with specificity of binding to certain monosaccharides or oligosaccharides. They can detect abnormal glycosylation patterns on immunoglobulins in patients with various chronic inflammatory diseases, including rheumatoid arthritis and IgA nephropathy (IgAN). However, lectins exhibit binding heterogeneity, depending on their source and methods of isolation. To characterize potential differences in recognition of terminal N acetylgalactosamine (GalNAc) on IgA1, we evaluated the binding characteristics of several commercial preparations of GalNAc-specific lectins using a panel of IgA1 and, as controls, IgA2 and IgG myeloma proteins. These lectins originated from snails Helix aspersa (HAA) and Helix pomatia (HPA), and the plant Vicia villosa (VV). Only HAA and HPA bound exclusively to IgA1, with its O-linked glycans composed of GalNAc, galactose, and sialic acid. In contrast, VV reacted with sugars of both IgA subclasses and IgG, indicating that it also recognized N linked glycans without GalNAc. Furthermore, HAA and HPA from several manufacturers differed in their ability to bind various IgA1 myeloma proteins and other GalNAc-containing glycoproteins in ELISA and Western blot. For serum samples from IgAN patients, HAA was the optimal lectin to study IgA1 glycosylation in ELISA and Western blot assays, including identification of the sites of attachment of the aberrant glycans. The galactose-deficient glycans were site-specific, localized mostly at Thr228 and/or Ser230. Because of the heterogeneity of GalNAc-specific lectins, they should be carefully characterized with appropriate substrates before undertaking any study. PMID- 17275908 TI - Intravitreal long-acting gas in the prevention of early postoperative vitreous hemorrhage in diabetic vitrectomy. AB - OBJECTIVE: To evaluate the hemostatic effects of intravitreal infusion of 10% C3F8 in patients undergoing diabetic vitrectomy on the occurrence of early postoperative recurrent vitreous hemorrhage. DESIGN: Prospective, randomized, observational case series. PARTICIPANTS: Sixty-one eyes (59 patients) that underwent primary pars plana vitrectomy for complications of proliferative diabetic retinopathy from September 2004 to April 2005, with postoperative retinal reattachment > or = 3 months and follow-up > 6 months were enrolled. METHODS: Sixty-one cases were randomly divided into either group 1 (intravitreal 10% C3F8 infusion at the end of surgery) or group 2 (no intravitreal gas). Ultrasound biomicroscopy (UBM) examination of the 3 sclerotomy sites was performed at > or = 2 months postoperatively. Demographic data, history, intraoperative findings, and management of recurrent vitreous hemorrhage were recorded. MAIN OUTCOME MEASURES: Initial time to vitreous clearing (ITVC), percentage of prolonged ITVC (> 5 weeks), and early (< or = 4 weeks) versus late (> 4 weeks) manifest postoperative recurrent vitreous hemorrhage in groups 1 and 2 were compared to determine the effects of 10% C3F8 on prevention of early recurrent vitreous hemorrhage. Multiple logistic regression analyses were performed to examine risk factors related to early recurrent vitreous hemorrhage. RESULTS: Group 1 ITVC was 13.2+/-9.6 days, and group 2 ITVC was 11.3+/-11.1 days (P = 0.26). Prolonged ITVC (> 5 weeks) in each group was 1/31 (3.2%) and 2/30 (6.7%; P = 0.53). Early manifest recurrent vitreous hemorrhage rates in groups 1 and 2 were 0/31 (0%) and 5/30 (16.7%), respectively (P = 0.02). Early manifest recurrent hemorrhage plus prolonged ITVC in the 2 groups were 1/31 (3.2%) and 7/30 (23.3%), respectively (P = 0.02). The incidences of elevated intraocular pressure, iris neovascularization, and significant cataract formation among the 2 groups were too low to detect statistical significance. No evidence of fibrovascular ingrowth was found by UBM examination in either group. Multiple logistic regression analyses in non-gas-infused cases showed that an increased extent of membrane peeling raised the possibility of significant early vitreous rebleeding. CONCLUSIONS: Intraocular tamponade with 10% C(3)F(8) may be a useful adjunct to vitrectomy for proliferative diabetic retinopathy in the reduction of early postoperative recurrent vitreous hemorrhage. PMID- 17275909 TI - Long-term study of Artisan phakic intraocular lens implantation for the correction of moderate to high myopia: ten-year follow-up results. AB - PURPOSE: To determine the long-term performance of the Artisan phakic intraocular lens (PIOL) for the correction of myopia. DESIGN: Long-term (10 years) retrospective follow-up study. PARTICIPANTS: Eighty-nine eyes of 49 patients who underwent Artisan PIOL implantation for the correction of myopia. METHODS: Comparisons were made between preoperative clinical data and the clinical data at 1, 6, and 10 years after surgery. MAIN OUTCOME MEASURES: Refractive stability, refractive predictability, safety, efficacy, best-corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), intraocular pressure, intraoperative problems, corneal endothelial cell density, corneal endothelial cell loss, and glare levels were evaluated. RESULTS: The mean spherical equivalent (SE) after 10 years was 0.70+/-1.00 diopters (D; range, -4.00 to 2.00 D), with no significant change in mean SE between 1, 6, and 10 years. At 10 years, 68.8% of all eyes were within 1.0 D of the intended correction. At 10 years, 31.2% (n = 24) gained 1 or more Snellen lines of BCVA and 2.6% (n = 2) lost more than 2 Snellen lines of BCVA; 93.3% reached a BCVA of 20/40 or better, and 82.0% reached a UCVA of 20/40 or better. The mean intraocular pressure remained stable and was 15.5+/-3.5 mmHg (range, 7-25 mmHg) at 10 years. The mean endothelial cell loss was -8.86+/-16.01% (range, -51.69% to 34.43%) at 10 years. CONCLUSIONS: Long-term results demonstrate that the implantation of an Artisan PIOL for the correction of moderate to high myopia is a stable, predictable, and safe method when strict inclusion criteria for surgery are applied. There was no significant loss of corneal endothelial cells and no reports of long-term glare. PMID- 17275910 TI - Analysis of macular edema after cataract surgery in patients with diabetes using optical coherence tomography. AB - OBJECTIVE: To assess the incidence or progression of macular edema (ME) after cataract surgery in diabetic patients using optical coherence tomography (OCT) and correlating this with degree of diabetic retinopathy or other risk factors. DESIGN: Prospective cohort study. PARTICIPANTS: Fifty diabetic eyes undergoing cataract surgery. METHODS: Each eye underwent 7-field fundus photography no more than 3 months before surgery. Optical coherence tomography testing was performed within 4 weeks before surgery and at 1- and 3-month postoperative visits. Best corrected visual acuity (BCVA) was recorded at each visit. Macular edema was defined as an increase of center point thickness on OCT > 30% from preoperative baseline. MAIN OUTCOME MEASURES: Changes in foveal thickness and BCVA. RESULTS: The incidence of ME on OCT was 22% (95% confidence interval, 13%-35%). The average increase in center point thickness at 1 month for eyes with ME was 202 microm, which resulted in a nearly 1-line loss of vision (0.07 logarithm of the minimum angle of resolution [logMAR] units) compared with eyes without ME gaining >2 lines of vision (0.24 logMAR units) (P>0.001). Eyes with no diabetic retinopathy developed minimal thickening of 18 mum and 14 mum at 1 and 3 months, respectively, associated with approximately 2 and 3 lines of improved vision, respectively (0.22 and 0.26 logMAR units). Eyes with moderate or severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy developed thickening of 145 mum and 131 mum at 1 and 3 months, respectively, associated with <1 and 2 lines of improved visual acuity, respectively (0.08 and 0.17 logMAR units). This difference (P = 0.05) in thickening (127 microm and 117 mum at 1 and 3 months, respectively) was correlated inversely with visual improvement (r = -0.662). Both duration of diabetes > or = 10 years (P = 0.04) and insulin dependence (P = 0.007) were associated with reduced visual improvement. CONCLUSIONS: Diabetic eyes have a high incidence of increased center point thickness on OCT after cataract surgery, associated with a loss of vision at 1 month, with limited visual recovery at 3 months. Treatment to prevent this might improve outcomes in similar individuals after surgery. PMID- 17275911 TI - Phenotypic investigation of human eyes with transplanted autologous cultivated oral mucosal epithelial sheets for severe ocular surface diseases. AB - PURPOSE: To determine the epithelial lineage of origin of surgically removed grafts after autologous cultivated oral mucosal epithelial transplantation (COMET). DESIGN: Retrospective comparative case series. PARTICIPANTS: We studied 6 eyes from 5 patients with total corneal stem cell destruction; 3 eyes were from patients with Stevens-Johnson syndrome and 3 eyes had sustained chemical injury. METHODS: Autologous cultivated oral mucosal epithelial sheets on human amniotic membrane (AM) were transplanted onto the ocular surface. Regrafting (2 eyes) or penetrating keratoplasty (4 eyes) was performed after the initial transplantation procedure for further visual rehabilitation. MAIN OUTCOME MEASURES: The excised grafts were subjected to clinical evaluation and to light, scanning, and transmission electron microscopic (EM) study and to immunohistochemical analysis. RESULTS: In clinically failed grafts, EM and immunohistochemical analysis disclosed only small areas where the original cultivated oral epithelial cells persisted. Neighboring conjunctival epithelial cells had apparently invaded a large portion of the corneal surface (keratin 3[-], Muc5ac[+]); there were many blood vessels and inflammatory cells. In clinically successful grafts, transplanted cultivated oral epithelial cells survived and had adapted well to the host corneal tissues (keratin 3[+], Muc5ac[-]); there was no infiltration by inflammatory cells, nor was there dissolution of the AM substrate. CONCLUSIONS: We posit that the process of graft opacification after COMET is responsible for the loss of transplanted cultivated oral epithelial cells and that this is followed by conjunctival cell invasion onto the corneal surface. We confirmed that in clinically successfully grafted eyes, autologous cultivated oral epithelial cells survived on the corneal surface and maintained ocular surface integrity. PMID- 17275912 TI - Influence of Cr(III) and Cr(VI) on the interaction between sparfloxacin and calf thymus DNA. AB - Cr(III) and Cr(VI) have different binding capacity with sparfloxacin, and have different combination modes with calf thymus DNA. Selecting these two different metal ions, the influence of them on the binding constants between sparfloxacin (SPFX) and calf thymus DNA, as well as the related mechanism has been studied by using absorption and fluorescence spectroscopy. The result shows that Cr(III) has weaker binding capacity to SPFX in the SPFX-Cr(III) binary system, but influences the binding between SPFX and DNA obviously in SPFX-DNA-Cr(III) ternary system. However, although Cr(VI) has a stronger binding capacity to SPFX, it has no effect on the binding between SPFX and DNA. Referring to the different modes of Cr(III) and Cr(VI) binding to DNA, the mechanism of the influence of metal ions on the binding between SPFX and DNA has been proposed. SPFX can directly bind to DNA by chelating DNA base sites. If a metal ion at certain concentration binds mainly to DNA bases, it can decrease the binding constants between SPFX and DNA through competing with SPFX. While if a metal ion at certain concentration mainly binds to phosphate groups of DNA, it can increase the binding constants by building a bridge between SPFX and DNA. If a metal ion at certain concentrations binds neither to bases nor phosphate groups in DNA, it will have no effect on the binding constant between SPFX and DNA. Our result supports Palumbo's conclusion that the binding between SPFX and the phosphata groups is the precondition for the combination between SPFX and DNA, which is stabilized through stacking interactions between the condensed rings of SPFX and DNA bases. PMID- 17275913 TI - Influence of the nature of quantum dot surface cations on interactions with DNA. AB - Quantum dots are semiconductor nanoparticles that are approximately 1-10nm in diameter, similar to small proteins, and their photoluminescence is sensitive to the presence and nature of adsorbates. We have deployed these nanomaterials as luminescent probes of DNA structure. Sequence dependent conformational flexibility of DNA is of great interest due to its implications for drug-DNA and DNA-protein interactions. The counterion atmosphere surrounding DNA plays an important role in its structure, dynamics, and packaging. In this paper, we investigate the effect that various monovalent and divalent cations have on the binding of 4.5 nm CdS quantum dots to oligonucleotides that have sequence directed intrinsic structure. PMID- 17275914 TI - Effect of active site and surface mutations on the reduction potential of yeast cytochrome c peroxidase and spectroscopic properties of the oxidized and reduced enzyme. AB - The reduction potentials of 22 yeast cytochrome c peroxidase (CcP) mutants were determined at pH 7.0 in order to determine the effect of both heme pocket and surface mutations on the Fe(III)/Fe(II) redox couple of CcP, as well as to determine the range in redox potentials that could be obtained through point mutations in the enzyme. Spectroscopic properties of the Fe(III) and Fe(II) forms of the mutant enzymes are also reported. The mutations include variants in the distal and proximal heme pockets as well as on the enzyme surface and involve single, double, and triple point mutations. A spectrochemical redox titration technique used in this study gave an E(0') value of -189 mV for yeast CcP compared to a previously reported value of -194 mV determined by potentiometry [C.W. Conroy, P. Tyma, P.H. Daum, J.E. Erman, Biochim. Biophys. Acta 537 (1978) 62-69]. Both positive and negative shifts in the reduction potential from that of the wild-type enzyme were observed, spanning a range of 113 mV. The His-52-->Asn mutation gave the most negative potential, -259 mV, while a triple mutant in which the three distal pocket residues, Arg-48, Trp-51, and His-52, were all converted to leucine residues gave the most positive potential, -146 mV. PMID- 17275916 TI - Neurobiology of animal models of attention-deficit hyperactivity disorder. AB - Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous, highly heritable, disorder resulting from complex gene-gene and gene-environment interactions. The defining symptoms of hyperactivity, impulsivity and impaired sustained attention are not unique to ADHD. It is therefore not surprising that animals with distinctly different neural defects model the behavioural characteristics of the disorder. Consistent with ADHD being a developmental disorder, animal models are either genetic (spontaneously hypertensive rats (SHR), dopamine transporter (DAT) knock-out mice, SNAP-25 mutant mice, mice expressing a mutant thyroid receptor) or have suffered an insult to the central nervous system during the early stages of development (anoxia, 6 hydroxydopamine). It appears that neural transmission is impaired by either direct disruption of dopaminergic transmission or a more general impairment of neurotransmission that gives rise to compensatory changes in monoaminergic systems that are not sufficient to completely normalize neural function. In general, results obtained with animal studies suggest that dopamine neurons are functionally impaired. However, evidence obtained from some animal models suggests that the noradrenergic and serotonergic neurotransmitter systems may be the target of drugs that ameliorate ADHD symptoms. PMID- 17275917 TI - Gender dimorphism in the myeloid differentiation of bone marrow precursor cells in a murine host bearing a T cell lymphoma. AB - Little information is available regarding the existence of gender dimorphism of tumor growth for most types of tumors. In a previous report we have demonstrated the existence of gender dimorphism in the growth of a murine T cell lymphoma, designated as Dalton's lymphoma (DL); moreover, tumor-associated macrophages (TAM) were found to play a central role in the manifestation of gender dimorphism observed in the growth of this T cell lymphoma. In view of these observations, the present investigation was undertaken to study if gender dimorphism in the growth of a T cell tumor also could be associated with a gender-dependent differential myelopoiesis of bone marrow cells. We have demonstrated the existence of a gender dimorphism in the proliferation, apoptosis and myeloid differentiation of bone marrow cells obtained from male and female tumor-bearing hosts. Androgen and estrogen were found to alter directly the growth properties of bone marrow cells, as also determined by the use of receptor antagonists of these hormones, flutamide and tamoxifen. Bone marrow cells of male and female tumor-bearing hosts also showed a differential expression of the cell cycle and apoptosis regulatory protein p53 and macrophage-colony stimulating factor (M-CSF) genes. Bone marrow cells of male tumor-bearing hosts showed a predominant differentiation in the macrophage lineage whereas those of female tumor-bearing mice were in the granulocyte lineage. Bone marrow-derived macrophages (BMDM) from male and female tumor-bearing mice also showed the existence of gender dimorphism with respect to their differentiation and activation. These observations are of clinical significance with respect to understanding of the host-tumor relationship at the level of gender dimorphism of myelopoiesis. PMID- 17275918 TI - Adjuvant effect of green propolis on humoral immune response of bovines immunized with bovine herpesvirus type 5. AB - Despite recent technological advances in vaccine production, most vaccines depend on the association with adjuvant substances. In this study, propolis, which has been attracting the attention of researchers due to its bioactive properties, was evaluated as an immunological adjuvant. The association of 40mg/dose of an ethanolic extract of green propolis with an inactivated oil vaccine against bovine herpesvirus type 5 (BoHV-5), resulted in a significant increase (P<0.01) in the neutralizing antibody levels, comparing to the bovines that received the same vaccine without propolis. Besides, propolis increased the percentage of animals with high antibody titers (above 32). Phenolic compounds such as artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) and the derivatives of cinnamic acid besides other flavonoid substances were abundant in the propolis extract used, and they could be the main substances with adjuvant action. The effect of the green propolis extract on the humoral immune response can be exploited in the development of new vaccines. PMID- 17275919 TI - Antibody and skin-test responses of sheep vaccinated against Johne's Disease. AB - Current vaccines against Mycobacterium avium subsp. paratuberculosis (MAP, Johne's Disease) may cause animals to react positively when tested for Mycobacterium bovis (Bovis). Therefore, the effects of vaccination on MAP serum Ab and skin-test responses to MAP and Bovis PPD were compared in 25 ewes vaccinated against MAP with 24 control ewes in an infected flock 3 years post vaccination. MAP-specific Ab levels were higher (P<0.001) in vaccinated ewes than in control ewes. All increases in skinfold-thickness from 0 to 48h were greater (P<0.0001) than zero while increases in skinfold-thickness from 48 to 72h were greater (P<0.05) than zero for Johnin but not for Bovis PPD. The Vaccine x PPD x Time interaction for skinfold-thickness was significant (P<0.001) with greater increases to Johnin than to Bovis, but with much greater increases in vaccinated ewes. These data suggest that administration of vaccines against MAP developed from whole organisms increase the likelihood that animals will be classified as "responders" to a Bovis screening test and negative by the follow-up comparative cervical tuberculin test, but they also show that vaccination initiates both humoral and cell-mediated MAP-specific responses. PMID- 17275915 TI - Leptin: at the crossroads of energy balance and systemic inflammation. AB - In addition to playing a central role in energy homeostasis, leptin is also an important player in the inflammatory response. Systemic inflammation is accompanied by fever (less severe cases) or hypothermia (more severe cases). In leptin-irresponsive mutants, the hypothermia of systemic inflammation is exaggerated, presumably due to the enhanced production and cryogenic action of tumor necrosis factor (TNF)-alpha. Mechanisms that exaggerate hypothermia can also attenuate fever, particularly in a cool environment. Another common manifestation of systemic inflammation is behavioral depression. Along with the production of interleukin (IL)-1beta, this manifestation is exaggerated in leptin irresponsive mutants. The enhanced production of TNF-alpha and IL-1beta may be due, at least in part, to insufficient activation of the anti-inflammatory hypothalamo-pituitary-adrenal axis by immune stimuli in the absence of leptin signaling. In experimental animals and humans that are responsive to leptin, suppression of leptin production under conditions of negative energy balance (e.g., fasting) can exaggerate both hypothermia and behavioral depression. Since these manifestations aid energy conservation, exaggeration of these manifestations under conditions of negative energy balance is likely to be beneficial. PMID- 17275920 TI - Rapid up-regulation of c-FLIP expression by BCR signaling through the PI3K/Akt pathway inhibits simultaneously induced Fas-mediated apoptosis in murine B lymphocytes. AB - Cross-linking of BCR rapidly induces protection of B cells from Fas-mediated apoptosis, which has been assumed one of the important survival mechanisms of B cells during antigen stimulation. In the mouse B cell line A20, which is sensitive to Fas-mediated apoptosis, stimulation of BCR inhibited apoptosis induced via Fas upstream of caspase-8 activation with an associated rapid increase in the expression of both short and long forms of cellular caspase 8/FLICE-inhibitory protein (c-FLIP). The c-FLIP competitively inhibited the recruitment of caspase-8 to the death-inducing signaling complex (DISC), which took as long as 3h to form after the stimulation of Fas in A20 cells. Knockdown of c-FLIP by a short hairpin RNA-expressing method rendered BCR-stimulated A20 cells sensitive to Fas-mediated apoptosis. The BCR-induced rapid expression of c FLIP was not affected by inactivation of NF-kappaB, but was inhibited by either treatment with a PI3K inhibitor, LY294002, or expression of a dominant negative PI3K p85 subunit, both of which suppressed phosphorylation of Akt and sensitized BCR-stimulated A20 cells to Fas-mediated apoptosis. Overexpression of constitutively active Akt was shown not only to up-regulate c-FLIP expression but also to render A20 cells resistant to Fas-mediated apoptosis. Moreover, treatment with LY294002 also suppressed BCR-induced up-regulation of c-FLIP expression in spleen B cells. Taken together, BCR-stimulation was shown to rapidly trigger a survival signal against simultaneously or ongoingly stimulated Fas-mediated apoptosis by promoting a PI3K/Akt signaling pathway-mediated up-regulation of c FLIP expression. PMID- 17275921 TI - Neutrophils invade lumbar dorsal root ganglia after chronic constriction injury of the sciatic nerve. AB - To test whether neutrophils (PMN) target lumbar dorsal root ganglia (DRG) following axonal injury leading to neuropathic pain, we visualized PMN infiltration in DRG tissue sections and estimated PMN count by flow cytometry following sciatic chronic constriction injury (CCI). Seven days after CCI, results show PMN within DRG where their count increased by three fold ipsilateral to injury compared to contralateral or sham, concomitant with peak neuropathic pain behavior. Superoxide burst in PMN isolated from rats d7 after CCI was elevated by 170% +/-18 compared to naive and MCP-1 mRNA expression in DRG increased by 8.9+/-2.9 fold, but that of MIP-2, CINC-1, and RANTES did not change. We conclude that CCI causes PMN invasion of the DRG whereby the functional implication of their close proximity to neuronal axon and soma remains unknown. PMID- 17275924 TI - The etiology of medial migration of tympanostomy tubes. PMID- 17275927 TI - Balance sensory organization in children with profound hearing loss and cochlear implants. AB - OBJECTIVES: (1) To determine the feasibility of the use of a modified postural control test under altered sensory conditions in children over 8 years of age, and (2) to assess how deaf children use sensory information for postural control when they have normal or abnormal vestibular responses, and if hearing input from a unilateral cochlear implant, changes their postural behavior. PATIENTS: We selected 36 children, 8 to 11 years of age, with congenital or early-acquired profound sensorineural hearing loss, 13 of them with unilateral cochlear implantation and 22 normal-hearing children. METHODS: The Postural Control (PC) test consists of a force platform with 2 stimulation paradigm conditions: (1) standing on the platform with opened eyes; (2) standing on foam placed on the force platform with closed eyes. Implanted children were tested with the implant turn on and turn off in this condition, in order to evaluate eventual change in the postural control parameters when they have hearing habilitation. The body center of pressure distribution area (COP) and the body sway velocity (SV) were the parameter to evaluate the postural control. RESULTS: Deaf children were classified into two groups according with the vestibular responses: group A (n=28) Children with normal vestibular rotary responses; group B (n=8) children with hypoactive responses. Children in group A had diagnoses of syndromic and non syndromic hereditary deafness, and children in group B had inner ear malformations, post-meningitis deafness, and one child had non-syndromic hereditary deafness with hypoactive vestibular response. In condition 1, when vestibular, somatosensory and visual information were enabled, the COP and SV values did not show any statistically significant differences between groups A, B and control. In condition 2, when visual information was removed and the somatosensory input strongly modified by standing on the foam, group B showed significant higher COP and SV values than groups A and control (p<0.05). In addition, the scalograms by wavelets of children in group B had higher amplitudes increasing the sway frequencies contents up to 3 Hz, not allowing them to maintain the up right stance in similar stimulation than in condition. Implanted children of the group A and B with the implant turn on, in the condition 2, did not show any significant difference in the SV, comparing when they had the implanted turn off. Group A p=0.395 and group B p=0.465 (Wilcoxon ranked test). CONCLUSION: These findings allow us to confirm that this postural test can be performed in children over 8 years old. Also our results suggest that deaf children with associated hypoactive vestibular responses included in our study, despite the etiology of the deafness, primarily use visual and somatosensory information to maintain their postural control. Hearing habilitation with a unilateral cochlear implant has no effect on the observed sensory organization strategy. PMID- 17275926 TI - Evaluation of early postoperative morbidity in pediatric tonsillectomy with the use of sucralfate. AB - OBJECTIVE: The objective of this study is to evaluate the efficacy of sucralfate in alleviating posttonsilectomy morbidity in a pediatric group of patients. METHODS: A prospective, double-blind, randomized, and placebo-controlled study comparing the irrigation of a solution containing either 1g of sucralfate (study group) or 1g of lactulose (control group) was performed on 69 children aged 3-12 years, who underwent tonsillectomy at the University Hospital of Brasilia Medical School. The children were randomly assigned and each one used a solution containing sucralfate or lactulose to swish and swallow four times daily during 7 days. Eleven patients were excluded. The anesthetic was standardized and no premedication was used. Pain magnitude using an "Oucher" scale, nausea, vomiting, bleeding, earache, analgesic drug intake, changes in the interincisor teeth distance, and changes in the weight and temperature were assessed by the surgeon 6, 24h, and 7 days after the surgery. RESULTS: Patients in the study group had significantly lower pain scores in the initial 6 postoperative hours (p<0.05). The difference between the two groups was not statistically significant for the other periods following the procedure or on the evaluation of the other indices. CONCLUSIONS: The use of the sucralfate in pediatric patients undergoing tonsillectomy was not effective in reducing the postoperative morbidity according to the parameters used in this study. The surgical technique with careful mucosal dissection associated with postoperative caries could be more important in the reduction of posttonsilectomy morbidity. PMID- 17275928 TI - Nasal symptoms and signs in children suffering from asthma. AB - OBJECTIVE: A link between the upper and lower airways has been convincingly demonstrated both in health and disease. To what extent the nose may be involved in children's asthma, has so far not been thoroughly investigated. In this study, we compared symptoms and signs from the upper airways in children with asthma and in children without to find out more about this. METHODS: The study group included 27 asthmatic children, the control group 29 age and sex-matched healthy volunteers. The children were investigated by a senior ENT-specialist. Their parents completed questionnaires about symptoms and signs of upper airway disorders. Skin prick tests, total IgE, acoustic rhinometry, and an X-ray of the epipharynx were performed. The data from the groups were compared. RESULTS: Nasal blockage, mouth breathing, day time sleepiness, apnoeas, itching, sneezing, and hearing impairment were more prevalent in asthmatics compared with controls (p<0.05). For nasal blockage the mean VAS-scores were 52.4 and 30.6 for asthmatics and controls, respectively. For daytime sleepiness the corresponding figures were 34.6 and 23.1. The adenoid-nasopharynx-index was larger, indicating reduced palatal airway in the former compared with the latter (p<0.05). CONCLUSIONS: As the site of upper airway obstruction in asthmatic children appears to be the epipharynx, the adenoids may play a key-role. PMID- 17275929 TI - Implications of ATP-binding cassette transporters for brain pharmacotherapies. AB - By preventing pharmacological compounds from achieving therapeutic levels in tissue, ATP-binding cassette (ABC) transporters complicate new drug discoveries. This has profound implications for pharmacotherapies, which go far beyond the need to deliver higher drug dosages. Comparative studies have recently shown that the expression and functionality of efflux proteins vary strongly both between species and strains, and in response to pathophysiological stimuli. This shatters hopes that it might become possible to predict drug biodistribution across species barriers. From this perspective, there is a need for more precise empirical biodistribution experiments to be performed in preparation for clinical trials. In such studies, the accumulation and elimination of drugs should be tested in various species under conditions resembling, as closely as possible, those in which a drug is clinically planned to be used. This approach should markedly enhance the overall success of new drugs and foster progress in neurological therapies. PMID- 17275930 TI - The developing use of heterozygous mutant mouse models in brain monoamine transporter research. AB - 5-Hydroxytryptamine (5-HT), dopamine and norepinephrine are important monoamine neurotransmitters implicated in multiple brain mechanisms and regulated by high affinity transmembrane monoamine transporters. Although knockout mice lacking 5 HT, dopamine or norepinephrine transporters are widely used to assess brain monoamine processes, these models have several methodological limitations. There is mounting evidence that heterozygous mutant mice with reduced (but not abolished) monoamine transporter functions could provide models with greater relevance to the genetics of human disorders, which only rarely involve complete loss-of-function mutations. Here, we discuss why heterozygous mouse models, in addition to knockout mice, might be useful for brain monoamine transporter research. PMID- 17275922 TI - Stimulation of prostaglandin E2-EP3 receptors exacerbates stroke and excitotoxic injury. AB - The effect of PGE(2) EP3 receptors on injury size was investigated following cerebral ischemia and induced excitotoxicity in mice. Treatment with the selective EP3 agonist ONO-AE-248 significantly and dose-dependently increased infarct size in the middle cerebral artery occlusion model. In a separate experiment, pretreatment with ONO-AE-248 exacerbated the lesion caused by N methyl-d-aspartic acid-induced acute excitotoxicity. Conversely, genetic deletion of EP3 provided protection against N-methyl-d-aspartic acid-induced toxicity. The results suggest that PGE(2), by stimulating EP3 receptors, can contribute to the toxicity associated with cyclooxygenase and that antagonizing this receptor could be used therapeutically to protect against stroke- and excitotoxicity-induced brain damage. PMID- 17275931 TI - Sodium sulphite enhances RNA isolation and sensitivity of Cucumber mosaic virus detection by RT-PCR in black pepper. AB - Isolation of intact high quality RNA suitable for RT-PCR from black pepper is greatly hindered by the presence of polyphenols and polysaccharides. These compounds adversely affect the sensitivity of virus detection by RT-PCR. The present study evaluated the effect of sodium sulphite in enhancing RNA yield and quality in a modified acid guanidium thiocyanate-phenol-chloroform (AGPC) protocol. The results were compared with the standard AGPC method and RNeasy Plant Mini Kit (Qiagen) for detection of Cucumber mosaic virus through RT-PCR. The addition of sodium sulphite in the extraction buffer increased the sensitivity of virus detection. Higher sensitivity of detection (than obtained from the kit) was seen when sodium sulphite was used at 0.5%. Similar levels of sensitivity were also observed for the detection of Cucumber mosaic virus from Piper longum. PMID- 17275932 TI - Inhibition of avian metapneumovirus (AMPV) replication by RNA interference targeting nucleoprotein gene (N) in cultured cells. AB - Avian metapneumovirus (AMPV) is the primary causative agent of severe rhinotracheitis in turkeys. It is associated with swollen head syndrome in chickens and is the source of significant economic losses to animal food production. In this study, we designed specific short interfering RNA (siRNA) targeting the AMPV nucleoprotein (N) and fusion (F) genes. Three days post-virus infection, virus titration, real time RT-PCR, and RT-PCR assays were performed to verify the effect of siRNA in AMPV replication. A marked decrease in virus titers from transfected CER cells treated with siRNA/N was observed. Also, the production of N, F, and G mRNAs in AMPV was decreased. Results indicate that N specific siRNA can inhibit virus replication. In future studies, a combination of siRNAs targeting the RNA polymerase complex may be used as a tool to study AMPV replication and/or antiviral therapy. PMID- 17275933 TI - Effects of aqueous exposure to polychlorinated biphenyls (Aroclor 1254) on physiology and behavior of smolt development of Atlantic salmon. AB - Polychlorinated biphenyls (PCBs) are a widespread aquatic contaminant and are present in both wild and hatchery raised Atlantic salmon, Salmo salar. The possible sub-lethal alterations in smolt physiology and behavior due to PCB exposure of salmon have not been widely examined. In this study, we examined the effects of the PCB mixture Aroclor 1254 on survival and smolt development of Atlantic salmon. In separate experiments, fish were exposed as yolk-sac larvae or as juveniles just prior to the parr-smolt transformation in April to 1 microgl( 1) (PCB-1) or 10 microgl(-1) (PCB-10) aqueous Aroclor 1254 (A1254), or vehicle for 21 days. After exposure, yolk-sac larvae were reared at ambient conditions for 1 year, until the peak of smolting the following May. Juveniles were sampled immediately after exposure. Both groups were assessed for behavioral, osmoregulatory, and endocrine disruption of smolt development at the peak of smolting. PCB-1 and PCB-10 treated yolk-sac larvae exhibited significant increases in the rate of opercular movement after 14 and 21 days of exposure. At the peak of smolting, prior exposure as yolk-sac larvae to PCB-1 did not affect behavior, while PCB-10 dramatically decreased volitional preference for seawater. Neither concentration of A1254 had long-term effects on the osmoregulatory or endocrine parameters measured in animals exposed as yolk-sac larvae. Juvenile fish exposed to PCB-1 or PCB-10 during smolting exhibited a dose-dependent reduction in preference for seawater. Fish treated with the higher dose of A1254 also exhibited a 50% decrease in gill Na(+),K(+)-ATPase activity and a 10% decrease in plasma chloride levels in freshwater. In addition, plasma triiodothyronine was reduced 35-50% and plasma cortisol 58% in response to exposure to either concentration; whereas plasma thyroxine, growth hormone, and insulin-like growth factor I levels were unaffected. These results indicate that the effects of exposure to A1254 may vary according to developmental stage. Exposure to A1254 in the freshwater environment can inhibit preparatory adaptations that occur during smolting, thereby reducing marine survival and sustainability of salmon populations. PMID- 17275934 TI - Toxicogenomic responses in rainbow trout (Oncorhynchus mykiss) hepatocytes exposed to model chemicals and a synthetic mixture. AB - As more salmon gene expression data has become available, the cDNA microarray platform has emerged as an appealing alternative in ecotoxicological screening of single chemicals and environmental samples relevant to the aquatic environment. This study was performed to validate biomarker gene responses of in vitro cultured rainbow trout (Oncorhynchus mykiss) hepatocytes exposed to model chemicals, and to investigate effects of mixture toxicity in a synthetic mixture. Chemicals used for 24h single chemical- and mixture exposures were 10 nM 17alpha ethinylestradiol (EE2), 0.75 nM 2,3,7,8-tetrachloro-di-benzodioxin (TCDD), 100 microM paraquat (PQ) and 0.75 microM 4-nitroquinoline-1-oxide (NQO). RNA was isolated from exposed cells, DNAse treated and quality controlled before cDNA synthesis, fluorescent labelling and hybridisation to a 16k salmonid microarray. The salmonid 16k cDNA array identified differential gene expression predictive of exposure, which could be verified by quantitative real time PCR. More precisely, the responses of biomarker genes such as cytochrome p4501A and UDP-glucuronosyl transferase to TCDD exposure, glutathione reductase and gammaglutamyl cysteine synthetase to paraquat exposure, as well as vitellogenin and vitelline envelope protein to EE2 exposure validated the use of microarray applied to RNA extracted from in vitro exposed hepatocytes. The mutagenic compound NQO did not result in any change in gene expression. Results from exposure to a synthetic mixture of the same four chemicals, using identical concentrations as for single chemical exposures, revealed combined effects that were not predicted by results for individual chemicals alone. In general, the response of exposure to this mixture led to an average loss of approximately 60% of the transcriptomic signature found for single chemical exposure. The present findings show that microarray analyses may contribute to our mechanistic understanding of single contaminant mode of action as well as mixture effects, but that its use in screening of complex environmental samples will need to be further evaluated. PMID- 17275935 TI - Amlodipine induced gingival hyperplasia: a rare entity. AB - Drug induced gingival hyperplasia is an uncommon entity. Anticonvulsants, immunosuppressants and calcium channel blockers are often implicated. We report a case of a 52-year old male who developed amlodipine induced gingival hyperplasia. The etiology and treatment modalities are discussed. PMID- 17275937 TI - The value of d-dimer in the diagnosis of acute aortic dissection. PMID- 17275936 TI - Late stent thrombosis after transcoronary transplantation of granulocyte-colony stimulating factor-mobilized peripheral blood stem cells following primary percutaneous intervention for acute myocardial infarction. AB - Transcoronary transplantation of autologous stem cells (ASC) can improve cardiac function after myocardial infarction. For ASC-propagation, granulocyte-colony stimulating factor (G-CSF) is widely used. However, a clinical long-term safety profile of combining G-CSF therapy and transcoronary ASC-transplantation does not exist. We report on three cases of late stent thrombosis in a cohort of 24 patients who had undergone intracoronary infusion of G-CSF-mobilized ASC after primary stenting for acute myocardial infarction. PMID- 17275938 TI - Does education affect smoking behaviors? Evidence using the Vietnam draft as an instrument for college education. AB - This paper tests the hypothesis that education improves health and increases people's life expectancy. It does so by analyzing the effect of education on smoking behaviors. To account for the endogeneity of smoking, the analysis develops an instrumental variable approach which relies on the fact that during the Vietnam War college attendance provided a strategy to avoid the draft. The results indicate that education does affect smoking decisions: educated individuals are less likely to smoke, and among those who initiated smoking, they are more likely to have stopped. PMID- 17275939 TI - Detection of parC mutations in Streptococcus pneumoniae by Real-time PCR and Taqman-MGB probes. AB - A Real-time PCR assay was developed by using Taqman-MGB probes to screen mutations at codons Ser79 and Asp83 of Streptococcus pneumoniae parC. One hundred and thirty levofloxacin-susceptible and forty-two levofloxacin-resistant clinical strains were assayed. Mutations at codon 79 were found among all the levofloxacin resistant strains. Mutations at codon 79 or 83 were found in ten levofloxacin susceptible strains. This procedure is a reliable method for a rapid detection of mutations in the QRDRs of parC gene of S. pneumoniae and could be carried out in a diagnostic laboratory for some high-risk patients or in epidemiological surveys. PMID- 17275940 TI - A comparison of hydrogen photoproduction by sulfur-deprived Chlamydomonas reinhardtii under different growth conditions. AB - Continuous photoproduction of H(2) by the green alga, Chlamydomonas reinhardtii, is observed after incubating the cultures for about a day in the absence of sulfate and in the presence of acetate. Sulfur deprivation causes the partial and reversible inactivation of photosynthetic O(2) evolution in algae, resulting in the light-induced establishment of anaerobic conditions in sealed photobioreactors, expression of two [FeFe]-hydrogenases in the cells, and H(2) photoproduction for several days. We have previously demonstrated that sulfur deprived algal cultures can produce H(2) gas in the absence of acetate, when appropriate experimental protocols were used (Tsygankov, A.A., Kosourov, S.N., Tolstygina, I.V., Ghirardi, M.L., Seibert, M., 2006. Hydrogen production by sulfur-deprived Chlamydomonas reinhardtii under photoautotrophic conditions. Int. J. Hydrogen Energy 31, 1574-1584). We now report the use of an automated photobioreactor system to compare the effects of photoautotrophic, photoheterotrophic and photomixotrophic growth conditions on the kinetic parameters associated with the adaptation of the algal cells to sulfur deprivation and H(2) photoproduction. This was done under the experimental conditions outlined in the above reference, including controlled pH. From this comparison we show that both acetate and CO(2) are required for the most rapid inactivation of photosystem II and the highest yield of H(2) gas production. Although, the presence of acetate in the system is not critical for the process, H(2) photoproduction under photoautotrophic conditions can be increased by optimizing the conditions for high starch accumulation. These results suggest ways of engineering algae to improve H(2) production, which in turn may have a positive impact on the economics of applied systems for H(2) production. PMID- 17275941 TI - An RNAi screening platform to identify secretion machinery in mammalian cells. AB - Integrative approaches to study protein function in a cellular context are a vital aspect of understanding human disease. Genome sequencing projects provide the basic catalogue of information with which to unravel gene function, but more systematic applications of this resource are now necessary. Here, we describe and test a platform with which it is possible to rapidly use RNA interference in cultured mammalian cells to probe for proteins involved in constitutive protein secretion. Synthetic small interfering RNA molecules are arrayed in chambered slides, then incubated with cells and an assay for secretion performed. Automated microscopy is used to acquire images from the experiments, and automated single cell analysis rapidly provides reliable quantitative data. In test arrays of 92 siRNA spots targeting 37 prospective membrane traffic proteins, our approach identifies 7 of these as being important for the correct delivery of a secretion marker to the cell surface. Correlating these findings with other screens and bioinformatic information makes these candidates highly likely to be novel membrane traffic machinery components. PMID- 17275942 TI - Fractionation of proteins with two-sided electro-ultrafiltration. AB - Downstream processing is a major challenge in bioprocess industry due to the high complexity of bio-suspensions itself, the low concentration of the product and the stress sensitivity of the valuable target molecules. A multitude of unit operations have to be joined together to achieve an acceptable purity and concentration of the product. Since each of the unit operations leads to a certain product loss, one important aim in downstream-research is the combination of different separation principles into one unit operation. In the current work a dead-end membrane process is combined with an electrophoresis operation. In the past this concept has proven successfully for the concentration of biopolymers. The present work shows that using different ultrafiltration membranes in a two sided electro-filter apparatus with flushed electrodes brought significant enhancement of the protein fractionation process. Due to electrophoretic effects, the filtration velocity could be kept on a very high level for a long time, furthermore, the selectivity of a binary separation process carried out exemplarily for bovine serum albumin (BSA) and lysozyme (LZ) could be greatly increased; in the current case up to a value of more than 800. Thus the new two sided electro-ultrafiltration technique achieves both high product purity and short separation times. PMID- 17275943 TI - Mechanisms controlling protein release from lipidic implants: effects of PEG addition. AB - Different types of tristearin-based implants for controlled rh-interferon alpha 2a (IFN-alpha) release were prepared by compression and thoroughly characterised in vitro. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was added as a co lyophilisation agent for protein stabilisation and different amounts of polyethylene glycol (PEG) as efficient protein release modifier. To get deeper insight into the underlying mass transport mechanisms, the release of IFN-alpha, HP-beta-CD and PEG into phosphate buffer pH 7.4 was monitored simultaneously and appropriate analytical solutions of Fick's second law of diffusion were fitted to the experimental results. Importantly, the addition of only 5-20% PEG to the lipidic implants significantly altered the resulting protein release rates and the relative importance of the underlying mass transport mechanisms. The release of IFN-alpha from PEG-free implants was purely diffusion controlled. In contrast, in PEG-containing devices other phenomena were also involved in the control of protein release: the IFN-alpha release rate remained about constant over prolonged periods of time and the total amounts of mobile IFN-alpha increased. Interestingly, the release of PEG itself as well as of HP-beta-CD from the implants remained purely diffusion controlled, irrespective of the amount of added PEG. Thus, different mass transport mechanisms govern the release of the drug, co-lyophilisation agent and release modifier out of the lipidic implants. PMID- 17275944 TI - Effective tumor regression by anti-neovascular therapy in hypovascular orthotopic pancreatic tumor model. AB - Pancreatic cancer is one of the most serious cancers with poor therapeutic results and prognosis. In here, we proposed a novel treatment strategy of pancreatic cancer by injuring limited angiogenic vessels with liposome containing adriamycin. At first, we established an orthotopic tumor model, which has a hypovascular characteristic of pancreatic tumor. In this model, we obtained the enhanced therapeutic efficacy with liposome that modified by polyethylene glycol (PEG) and a peptide, Ala-Pro-Arg-Pro-Gly (APRPG), having an affinity to neovessels. Histochemical analysis suggested the degradation of angiogenic vessels after treatment with APRPG-PEG-liposomal adriamycin. In addition, we observed colocalization of fluorescence-labeled APRPG-PEG-liposome with angiogenic endothelial cells, although the biodistribution of (3)H-labeled liposome did not show the difference in the amount of accumulation between PEG modified liposome and APRPG-PEG-modified liposome. These results suggested the availability of the anti-neovascular therapy against pancreatic cancer and supply a new sight indication on chemotherapeutics against pancreatic cancer. PMID- 17275945 TI - Effect of pioglitazone on atherogenic outcomes in type 2 diabetic patients: a comparison of responders and non-responders. AB - The aim of this study was to evaluate the anti-atherogenic efficacy of pioglitazone, a thiazolidinedione derivative, on the change in atherogenic outcomes by comparing responder and non-responder groups in type 2 diabetic patients. Twenty-three patients with poor diabetic control were treated with 15 mg of pioglitazone for 12 months. The levels of fasting plasma glucose (FPG), HbA1c, triglycerides (TG), total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) were measured monthly, and those of remnant-like particle-cholesterol (RLP-C) and lipoprotein (a) [Lp (a)] were measured every 3 months. In Month 6, the patients were divided into two groups according to the decrease in HbA1c level: the responder group showed a decrease of > or =1%; the non-responder group, a decrease of <1%. In the responder group, the levels of FPG and HbA1c decreased significantly after Month 3. The values of the body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) index, LDL-C, and RLP-C were significantly higher in the responder group than in the non-responder group. Although the levels of T-Cho and HDL-C were unchanged in both groups, those of TG and RLP-C were drastically reduced in the responder group. Interestingly, the relative change in Lp (a) was significantly decreased in both groups. These results strongly suggest that pioglitazone is beneficial for type 2 diabetic patients with high levels of BMI, HOMA-IR, LDL-C, and RLP-C, as it helps to prevent the progression of atherosclerosis, including coronary heart diseases. PMID- 17275946 TI - Objective quantification of acetylcholine receptor aggregation using fast Fourier transforms. AB - A new approach for objectively analyzing the aggregation of acetylcholine receptors (AChRs) through power spectrum analysis derived from fast Fourier transform (FFT) of images has been developed. Presently, detection of AChR aggregates at neuromuscular junctions is not easily accomplished. Though the formation of AChR clusters results in periodic gray-level variations that differ with time, no study reporting their correlation with frequency information in the Fourier domain for aggregates' detection purposes exists. To this end, we processed time-lapse images of AChR aggregates' formation on murine myotubes to extract peak values of power spectra. To validate interpretation of the Fourier spectra analysis, a computer routine was developed to semi-automatically count AChR aggregates. We found: (1) logarithmic maxima of Fourier spectra correlated significantly with experimentation time; (2) cluster count correlated significantly with time only after clusters were discernable from images, signifying that this method heavily depended on definitive growth data and thresholding values; (3) exponents of Fourier maxima versus time and cluster count versus time profiles during this phase compared favorably, indicating that both methods were analyzing identical cluster growth rates. Our observations suggest that analysis via FFT power spectrum is sensitive and robust enough to automatically quantify AChR aggregates. PMID- 17275948 TI - Chemical cues, defence metabolites and the shaping of pelagic interspecific interactions. AB - Several observations and model calculations suggest that chemically mediated interactions can structure planktonic food webs. However, only recently have improvements in chemical methods, coupled with ecological assays, led to the characterization of chemical cues that affect the behaviour and/or physiology of planktonic organisms. We are currently beginning to elucidate if or how chemical signals can directly affect the interactions between species and even shape complex community structures in aquatic systems. Here, we highlight recent research on the nature and action of chemical signals in the pelagic marine and freshwater environments, with an emphasis on kairomones and defence metabolites. PMID- 17275947 TI - Overexpression of Pin1 in non-small cell lung cancer (NSCLC) and its correlation with lymph node metastases. AB - BACKGROUND: Pin1 isomerizes the bonds of molecules important for numerous oncogenic and cell-signaling pathways, including Bcl-2, p53, c-Jun, beta-catenin, NF-kappaB, cyclin D1, c-Myc and Raf-1. This can cause a change in conformation leading to alterations in catalytic activity, protein-protein interactions, subcellular localization and protein stability. These alterations have been shown to be associated with cell transformation and cancer progression. Pin1 is overexpressed in several different human cancers. This is the first report of Pin1 overexpression in clinical samples of non-small cell lung cancer (NSCLC). METHODS: Protein expression levels of Pin1 in tumor and normal lung specimens were analyzed for expression of Pin1, cyclin D1, p53 and MDM2 using immunohistochemistry and compared to several clinicopathological characteristics. The mRNA expression of Pin1 was also analyzed using quantitative real-time RT-PCR and compared to clinicopathological characteristics. RESULTS: Pin1 protein was shown to be overexpressed in NSCLC tumor samples, and correlated with lymph node positive disease and tumor stage. High expression of MDM2 also correlated with lymph node positive disease and with poorly differentiated tumors. High expression of MDM2 also correlated with lymph node positive disease and with poorly differentiated tumors. High expression levels of Pin1 correlated with high levels of p53 or MDM2 protein, but did not show a correlation with cyclin D1. However, high levels of MDM2 correlated with cyclin D1 overexpression. Pin1 mRNA was expressed significantly more often in the tumors of smokers than of non smokers. The relationship between the expression of protein and mRNA of Pin1 has obviously showed that protein expression isn't significantly associated with mRNA expression. CONCLUSIONS: Pin1 is overexpressed in many different cancers, including NSCLC, and may possibly be used as a tumor marker or as a target for cancer therapy. PMID- 17275949 TI - Integrin alphavbeta6 mediates HT29-D4 cell adhesion to MMP-processed fibrinogen in the presence of Mn2+. AB - Mn(2+) was found to induce adhesion of HT29-D4 adenoma carcinoma cells to fibrinogen (Fb). This was independent of the expression of the beta3 integrin subunit and involved endogenous alphavbeta6 but not alphavbeta5 integrin. Thus, addition of Mn(2+) led to a change in integrin alphavbeta6 specificity. Furthermore, Mn(2+) was found to strongly activate the extracellular signal regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway in the HT29 D4 cell line. As a MAPK inhibitor strongly reduced the Mn(2+)-induced cell adhesion to Fb, it is suggested that a link between MAPK activation and cell adhesion to Fb exists. Both expression and activity of matrix metalloproteinase-9 (MMP-9) were enhanced by Mn(2+) and this led to Fb processing. MMP inhibitors prevented Mn(2+)-mediated cell adhesion to Fb, leading us to suggest that Mn(2+) promoted convergent changes in integrin alphavbeta6 conformation and Fb structure through activation of ERK/MAPK and MMP-9. Finally, we found that Mn(2+) and activators of the ERK pathway cooperated in HT29-D4 cell adhesion to Fb. Such a process may be involved in bone metastasis of some cancer cells. PMID- 17275950 TI - Expression pattern of Drosophila translin and behavioral analyses of the mutant. AB - Translin is an evolutionarily conserved approximately 27-kDa protein that binds to specific DNA and RNA sequences and has diverse cellular functions. Here, we report the cloning and characterization of the translin orthologue from the fruit fly Drosophila melanogaster. Under protein-denaturing conditions, purified Drosophila translin exists as a mixture of dimers and monomers just like human translin. In contrast to human translin, the Drosophila translin dimers do not appear to be stabilized by disulfide interactions. Drosophila translin shows a ubiquitous cytoplasmic localization in early embryonal syncytial stage, with an enhanced staining in ventral neuroblasts at later stages (8-9), which are probably at metaphase. An elevated expression was seen in several other cell types, such as cells around the tracheal pits in the embryo and oenocytes in the third instar larva. RNA in situ hybridization showed an increased expression in the ventral midline cells of the larval brain, suggesting a neuronal expression, which was corroborated by protein immunostaining. In adult flies, Drosophila translin is localized in the brain neuronal cell bodies and in early spermatocytes. Interestingly, Drosophila translin mutants exhibit an impaired motor response which is sex specific. Taken together, the multiple cellular localizations, the high neuronal expression and the attendant locomotor defect of the Drosophila translin mutant suggest that Drosophila translin may have roles in neuronal development and behavior analogous to that of mouse translin. PMID- 17275952 TI - Isolation measures for prevention of infection with respiratory pathogens in cystic fibrosis: a systematic review? PMID- 17275951 TI - Preventing apoptotic cell death by a novel small heat shock protein. AB - NCBI database analysis indicated that the human C1orf41 protein (small heat shock like protein-Hsp16.2) has sequence similarity with small heat shock proteins (sHsps). Since sHsps have chaperone function, and so prevent aggregation of denatured proteins, we determined whether Hsp16.2 could prevent the heat-induced aggregation of denatured proteins. Under our experimental conditions, recombinant Hsp16.2 prevented aggregation of aldolase and glyceraldehyde-3-phosphate dehydrogenase, and protected Escherichia coli cells from heat stress indicating its chaperone function. Hsp16.2 also formed oligomeric complexes in aqueous solution. Hsp16.2 was found to be expressed at different levels in cell lines and tissues, and was mainly localized to the nucleus and the cytosol, but to a smaller extent, it could be also found in mitochondria. Hsp16.2 could be modified covalently by poly(ADP ribosylation) and acetylation. Hsp16.2 over-expression prevented etoposide-induced cell death as well as the release of mitochondrial cytochrome c and caspase activation. These data suggest that Hsp16.2 can prevent the destabilization of mitochondrial membrane systems and could represent a suitable target for modulating cell death pathways. PMID- 17275953 TI - Monitoring the occurrence of wound infections after cardiac surgery. AB - The aim of this study was to demonstrate the use of a graphical method for real time monitoring of the occurrence of surgical wound infection following cardiac surgery. This included developing and incorporating a risk scoring system so that variations in case-mix could be duly accounted for in the monitoring process. We analysed routinely collected data from a London teaching hospital. These data consisted of records for 2146 patients who had undergone cardiac surgery between April 2000 and March 2004 and whose surgical wounds were followed up as part of the local surveillance programme. The risk model was developed using logistic regression analysis with surgical wound infection diagnosed before hospital discharge as the outcome measure. Factors included in the model were the number of surgical wounds, patient age, operations that combined bypass surgery and valve replacement, renal disease and the number of days between hospital admission and surgery. The model was a good predictor of outcomes recorded within an independent data set (Chi-squared=3.81, P=0.58) and we incorporated it into a graphical tool for monitoring outcomes. The risk model and the associated graphical monitoring method could be valuable tools to assist with infection management. If used in real-time, problems with the care process can be quickly identified allowing timely remedial action to be taken. PMID- 17275954 TI - Healthcare-associated infection among residents of long-term care facilities: a cohort and nested case-control study. AB - Knowledge of infection control measures in nursing homes is limited. This study aimed to assess the incidence of, and potential risk factors for, healthcare associated infection in long-term care facilities in Norway. Incidence of healthcare-associated infection was recorded prospectively in six long-term care facilities located in two major cities in Norway between 1 October 2004 and 31 March 2005. For each resident with an infection we aimed for two controls in a nested case-control study to identify potential risk factors. Incidence of infection was 5.2 per 1000 resident-days. Urinary and lower respiratory tract infections were the most common. Patients confined to their beds [odds ratio (OR=2.7)], who stayed <28 days (OR=1.5), had chronic heart disease (OR=1.3), urinary incontinence (OR=1.5), an indwelling urinary catheter (OR=2.0) or skin ulcers (OR=1.8) were shown to have a greater risk for infection. Age, sex and accommodated in a two- versus single-bed room were not significant factors. Incidence of infection in nursing homes in Norway is within the range reported from other countries. This study identified several important risk factors for healthcare-associated infection. There is a need to prevent infection by implementing infection control programmes including surveillance in long-term care facilities. PMID- 17275955 TI - An outbreak of catalase-negative methicillin-resistant Staphylococcus aureus. AB - The wide dissemination of a major epidemic methicillin-resistant Staphylococcus aureus (MRSA) clone in Brazilian hospitals (Brazilian clone) limits the value of molecular typing techniques such as pulsed-field gel electrophoresis (PFGE) for outbreak investigation. We report the first outbreak of a catalase-negative strain of MRSA, which was initially detected by the unusual result of this phenotypical test. The outbreak occurred in the Hospital Sanatorinhos de Carapicuiba, a 237-bed secondary hospital located in Sao Paulo, Brazil. From May to August 2002, a total of 11 MRSA isolates were recovered from four patients in the intensive care unit. All the isolates were catalase negative and susceptible only to vancomycin and linezolid. Three of the four patients eventually died. Molecular typing demonstrated an indistinguishable PFGE pattern among the 11 isolates, with similarities to the Brazilian clone and the hospital's usual MRSA strain. This report emphasizes the importance of an uncommon phenotypical result as a marker for initiating an outbreak investigation and should encourage clinical laboratories to recognize and report such isolates. PMID- 17275956 TI - Isolation facilities for patients with methicillin-resistant Staphylococcus aureus (MRSA): how adequate are they? PMID- 17275957 TI - Breaking the cycle. PMID- 17275958 TI - Needle protective devices. PMID- 17275959 TI - Prevalence of hospital infection and antibiotic use at a university medical center in Hong Kong. AB - Hospital infection prevalence surveys were performed in our 1400-bed University medical centre in Hong Kong from 1985 to 1988. We investigated the rates of four major hospital-acquired infections (HAIs) (pneumonia, symptomatic urinary tract infection, surgical site infection and laboratory-confirmed bloodstream infection) in order to identify current distribution and any changes after 15 years. A one-day point prevalence study was performed on 7 September 2005. All inpatients were surveyed for HAIs, community-acquired infections (CAIs), risk factors, pathogenic isolates and antibiotics prescribed. Infections were diagnosed according to Centers for Disease Control and Prevention (CDC) criteria. In total, 1021 patients were surveyed; of these, 41 had 42 HAIs (4% prevalence) and 389 (38%) were receiving antibiotics. The commonest HAI was pneumonia (1.4%) followed by bloodstream infection (0.9%) and symptomatic urinary tract infection (0.8%). The prevalence of postoperative surgical site infection was 5.6%. The nosocomial prevalence rate was highest in the Intensive Care Unit, followed by the Pediatric and Neonatal Intensive Care Units, Children's Cancer Centre/Bone Marrow Transplant Unit and Orthopaedics with Traumatology. Meticillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were the commonest pathogens. The rates are significantly lower than previously and reflect the increased resources for infection control made available following the outbreak of severe acute respiratory syndrome (SARS). PMID- 17275960 TI - The endemic situation of Enterobacter aerogenes and Enterobacter cloacae: you will only discover what you are looking for. PMID- 17275961 TI - Patient outcomes after simultaneous bilateral total hip and knee joint replacements. AB - Simultaneous arthroplasties are increasingly being performed during one single anaesthetic event. No national nosocomial surveillance systems have yet reported data on this issue. We compared patient populations undergoing bi- and unilateral total hip (THA) and total knee (TKA) arthroplasties in terms of two outcome variables, deep surgical site infections (SSI) and mortality, by analysing surveillance data from the Finnish Hospital Infection Programme (SIRO). A total of 8201 patients underwent 9831 total arthroplasties during 2001-2004. Of the prosthetic joints, 7.2% were inserted in a bilateral operation (range by hospital, 0.6-19.2%; range by procedure type, 5.2-9.9%). Patients who underwent bilateral operations were younger; more often males, and their ASA score was lower than those who underwent unilateral procedures. The rate of deep SSI in bi- and unilateral THAs and in bi- and unilateral TKAs was 0, 0.5, 1.0 and 0.9%, respectively. Following bilateral operations, four deep SSIs were detected, all from bilateral TKAs, three of which were on the second operative side. In these three cases, single doses of antimicrobial prophylaxis were administered 115, 155 and 218 min before incision (median time in unilateral operations: 47 min). According to multi-variate analysis, bilateral operations were not an independent risk factor for deep SSIs. Mortality did not differ between bi- and unilateral THAs or TKAs. Our surveillance data indicate that simultaneous bilateral surgery did not increase the risk of deep SSIs or death after THA and TKA. Bilateral operations may, however, require specific guidelines regarding antimicrobial prophylaxis. PMID- 17275963 TI - Candidal versus bacterial late-onset sepsis in very low birthweight infants in Israel: a national survey. AB - Candidal infections are one of the common causes of late-onset sepsis (LOS) among very low birthweight (VLBW) infants, and are associated with substantial morbidity and mortality. The aim of this study was to evaluate the perinatal and neonatal risk factors for fungal LOS compared with bacterial LOS in VLBW infants. This was a population-based observational study of VLBW infants in 28 neonatal intensive care units across Israel, with information on 11,830 infants born between 1995 and 2002 from the Israeli National VLBW infant database. The study population comprised 3054 infants with one or more episodes of LOS. Univariate analysis and logistic regression models were used to compare perinatal and neonatal risk factors between infants with fungal sepsis only (N=179) and those with bacterial sepsis only (N=2630). The mean birthweight and gestational age of infants with candidal LOS were significantly lower (940 g; 27.1 weeks) than those in the bacterial LOS group (1027 g; 28.3 weeks) (P<0.001). Logistic regression analysis showed that candidal sepsis, in contrast to bacterial sepsis, was independently associated with decreasing gestational age and bronchopulmonary dysplasia (BPD). In addition, BPD only [odds ratio (OR) 1.84; 95% confidence intervals (CI) 1.03-3.23] and BPD with postnatal steroid therapy (OR 2.66; 95% CI 1.59-4.46) were independently associated with an increased risk for candidal sepsis. PMID- 17275962 TI - Which specimens should be tested for Clostridium difficile toxin? PMID- 17275964 TI - 4-Methyl-1,2,3-selenadiazole-5-carboxylic acid amides: antitumor action and cytotoxic effect correlation. AB - Synthesis and cytotoxic activity of a series of 4-methyl-1,2,3-selenadiazole-5 carboxylic acid amides on human fibrosarcoma HT-1080, mouse hepatoma MG-22A, and mouse fibroblasts 3T3 cell lines are described. The correlation between compound LD(50) and 3T3 fibroblast cell line morphology was shown. In vivo evaluation of amides on mouse sarcoma S-180 confirms high antitumor activity (58-85%). PMID- 17275965 TI - Synthesis, stereochemistry and antimicrobial evaluation of some N morpholinoacetyl-2,6-diarylpiperidin-4-ones. AB - In a search for new leads towards potent antimicrobial agents, an array of novel N-morpholinoacetyl-2,6-diarylpiperidin-4-ones has been synthesized and their in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi and antifungal activity against Candida albicans, Rhizopus sp., Aspergillus niger and Aspergillus flavus were evaluated. Structure and stereochemistry of all the N-morpholinoacetyl-2,6 diarylpiperidin-4-ones have been analyzed using (1)H and (13)C NMR spectroscopic techniques. In all the cases, amide N-CO group is preferentially in coplanar orientation with respect to the dynamically averaged plane of the piperidone ring. Further, all the symmetrically substituted compounds 19, 23, 24, 26 and 27 are expected to adopt half boat conformations while other compounds 20-22 and 25 adopt twist-boat conformations. Structure-activity relationship results for these nine compounds have shown that compounds 26 and 27 exerted excellent antibacterial activity against all the bacterial strains used except 27 against S. aureus. Against C. albicans and A. flavus, compound 24 recorded excellent antifungal activities while against Rhizopus sp., compound 25 showed potent activities. The obtained results may be used as key step for the building of novel chemical compounds with interesting antimicrobial profiles comparable to that of the standard drugs. PMID- 17275966 TI - [Therapy of chronic non infectious uveitis]. AB - PURPOSE: Chronic non infectious uveitis represents two-thirds of the causes of chronic uveitis referred in tertiary referral ophthalmology centre. One case out of 5 may evolve towards blindness. Therapy should be discussed on the basis of the uveitis severity and the diagnosis; it uses topics or systemic drugs, mainly corticosteroids and immunosuppressors. CURRENT KNOWLEDGE AND KEY POINTS: Besides corticosteroids and ciclosporin, use of immunosuppressors and biotherapy in chronic non infectious uveitis is not an indication of the Autorisation de Mise sur le Marche. However, immunosuppressors and biotherapy were the subjects of several studies, although controlled studies are scarce. Controlled studies concerned cyclosporine, azathioprine and intravenous cyclophosphamide in Behcet's disease, ciclosporine and tacrolimus in uveitis of various causes. Therapy of chronic non infectious uveitis was recently enriched by new drugs: mycophenolate mofetil, initially used in transplantation, has its indications extended to systemic diseases; TNF inhibitors initially used in therapy of systemic diseases; interferon efficacy revealed in Behcet's disease is now used in uveitis due to other causes. FUTURE PROSPECTS AND PROJECTS: Controlled studies are suitable in order to determinate the respective part of immunosuppressors and biotherapies in the treatment of chronic non infectious uveitis. PMID- 17275967 TI - [Theoretical epidemiology and vaccine]. AB - BACKGROUND: We describe important findings in theoretical epidemiology related to mass vaccination, including herd immunity and vaccine efficacy measures. POINTS: Through a review of recent publications, we address the following questions: is there optimal vaccine coverage? Is it possible to achieve optimal coverage through individual choice? What are the consequences of a suboptimal vaccination? What is vaccine efficacy and how is it measured? PERSPECTIVES: These results define a framework for analysing how successful mass vaccination may be from a public health perspective. PMID- 17275969 TI - [Recurring syncope after colonoscopy]. PMID- 17275968 TI - [Screening of abdominal aortic involvement using Doppler sonography in active giant cell (temporal) arteritis at the time of diagnosis. A prospective study of 30 patients]. AB - BACKGROUND: Inflammatory involvement of extracranial large-sized arteries occurs in 10-20% of patients with giant cell (temporal) arteritis. Aortic involvement may reveal giant cell arteritis or occur as a late-onset complication, and represents one of the most serious manifestation of the disease with the risk of aortic dissection and/or aneurysm rupture. The thoracic aorta is more frequently involved but abdominal aortitis may also occur in giant cell arteritis. To date, few data are available about abdominal aorta changes at the initial stage of giant cell arteritis. PATIENTS AND METHODS: This prospective monocentric study was conducted between May 1998 and May 2002, and included 30 consecutive patients with biopsy-proven giant cell arteritis. Standard clinical and biological data were collected. Each patient underwent an abdominal aortic Doppler-sonography that looked for aneurysm, ectasia, thickening of the vascular wall, and hypoechoic halo around the aorta. RESULTS: Among the 30 patients of this study (25 women, 5 men, mean age 68.5 years), 4 (13%) had an abdominal aortic aneurysm, with a low diameter (23 to 27 mm), measuring 2 to 5.5 cm in length. A vascular wall thickening superior or equal to 3 mm was noted in 17 patients (68%). A 4 to 8 mm periaortic hypoechoic halo was found in 10 patients (33%). This halo was present in 3 out of the 4 patients with aneurysm. CONCLUSION: Aortic involvement is a potentially serious complication of giant cell arteritis. The question of a systematic screening of this complication remains open to discussion. Our study shows that Doppler sonography may detect morphological abnormalities on the abdominal aorta at the initial stage of giant cell arteritis. These abnormalities comprise mild aneurysms, thickening of the vascular wall and periaortic halo, which could correspond to inflammatory locations of the disease. Complementary studies are needed to assess their specificity and their seriousness. PMID- 17275970 TI - Is the organisation and structure of hospital postnatal care a barrier to quality care? Findings from a state-wide review in Victoria, Australia. AB - OBJECTIVE: to describe the structure and organisation of hospital postnatal care in Victoria, Australia. DESIGN: postal survey sent to all public hospitals in Victoria (n=71) and key-informant interviews with midwives and medical practitioners (n=38). SETTING: Victoria, Australia. PARTICIPANTS: providers of postnatal care in Victorian public hospitals. FINDINGS: there is significant diversity across Victoria in the way postnatal units are structured and organised and in the way care is provided. There are differences in numerous practices, including maternal and neonatal observations and the length of time women spend in hospital after giving birth. Although the benefits of continuity of care are recognised by health care providers, continuity is difficult to provide in the postnatal period. Postnatal care is provided in busy, sometimes chaotic environments, with many barriers to providing effective care and few opportunities for women to rest and recover after childbirth. The findings in this study can, in part, be explained by the lack of evidence that has been available to guide early postnatal care. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: current structures such as standard postnatal documentation (clinical pathways) and fixed length of stay, may inhibit rather than support individualised care for women after childbirth. There is a need to move towards greater flexibility in providing of early postnatal care, including alternative models of service delivery; choice and flexibility in the length of stay after birth; a focus on the individual with far less emphasis on care being structured around organisational requirements; and building an evidence base to guide care. PMID- 17275971 TI - The efficacy of midwifery role models. AB - AIM: to explore the influence of midwifery role models on the role that student midwives learn. DESIGN: a qualitative approach using specifically grounded theory, was adopted. Data were collected by means of unstructured tape-recorded interviews, and analysed using the constant comparative method. SETTING: South of England. PARTICIPANTS: 20 student midwives undertaking either an 18-month pre registration shortened programme or a 3-4-year long programme were included in the study, along with 17 midwives practising in a variety of settings. FINDINGS: students learn the role of midwife in a changing culture, in which some midwives practise autonomously and others continue to rely on doctors to make their decisions. Students emulate the role of the midwife with whom they work. This suggests that all midwives are effective role models. Midwives who demonstrate the role of handmaiden to the doctor are inappropriate role models. They perpetuate a culture of midwifery that neither meets professional expectations nor the needs of women. Because they have power, students emulate these role models when in their presence. Midwives who practise autonomously are appropriate and influential role models. From these role models, students learn how to become autonomous practitioners. They emulate the practice of these role models because they want to, and intimate that they will continue to do so when their name is entered on the Nursing and Midwifery Council Professional Register. IMPLICATIONS: if learning inappropriate behaviours are to be avoided, attention needs to be paid to role modelling. PMID- 17275972 TI - The spirituality of presence in midwifery care. AB - The quality of the relationship between the midwife and the woman is widely acknowledged to be of vital importance in pregnancy and childbirth. The authors argue that presence is the spiritual strength that enables midwives to fully actualise their relational capacity. Presence describes a special way of being there or being with the other person. In order to develop its meaning fully, reference is made to the concepts of responsibility (Martin Buber) and availability (Gabriel Marcel). Responsibility indicates a deep capacity to respond to the needs people have to be heard, understood, respected, and, when it is required, helped and supported. Availability refers to the willingness of a person to give of herself for the sake of others. The aim of this paper is to offer a fresh perspective on the nature of caring midwifery through the use of these unique perspectives on genuine presence. The research method used is an integration of the philosophical reflections with relevant personal reports from women. These reports have been gathered from the research of others. PMID- 17275973 TI - Wound healing after hand surgery in patients with systemic sclerosis--a retrospective analysis of 41 operations in 19 patients. AB - This retrospective study evaluates the results of 41 consecutive hand and forearm operations in 19 patients with systemic sclerosis performed between 1985 and 2000. The mean age of the patients was 50 (14-84) years. Twenty-seven operations were elective and 14 were acute, carried out for skin breakdown and/or skin necrosis. One minor wound healing problem occurred in the elective group. In the acute group, seven of 14 operations healed uneventfully. Four patients had necrosis/infections after surgery, which required further surgery. Two patients had repeated wound infections. Another patient only healed after he stopped smoking. In systemic sclerosis, surgery performed electively does not seem to have increased difficulty with wound healing. Even larger operations, such as wrist arthrodesis or wrist replacement, can be performed safely. In acute cases with spontaneous skin breakdown and/or necrosis and/or critically ischaemic fingers, wound healing is more precarious and several procedures may be necessary to achieve skin healing. PMID- 17275974 TI - Dupuytren's contracture: a cause of an irreducible traumatic dislocation of the proximal interphalangeal joint. PMID- 17275975 TI - Transient bone loss of distal radius and ulna following clean-cut tendon injuries, repair and passive mobilisation. AB - The aim of this study was to investigate whether there is any significant bone loss of the ulna and radius following acute tendon-artery-nerve clean-cut injuries at the wrist level which were repaired and rehabilitated by early passive mobilisation. Fifty-eight patients who underwent such operation were enrolled in this study. Patients in Group I (n=28) had primary tendon repairs alone, in Group II (n=15) primary tendon and nerve repairs and in Group III (n=15) primary tendon, nerve and artery repairs. Bone mineral density (BMD) measurements of the ulna and radius were obtained during the first week, the sixth week, the third month and the 12th month after operation. The results demonstrated that BMD decrease in the ulna was more common than in the radius. When compared with the first week BMD measurements, the highest reduction was seen in the sixth week in Group I and during the third month, when bone loss of both the radius and ulna was considerable in Group II. The bone loss in all groups and subgroups were found to have recovered at the 12th month measurements, except in the distal region of the ulna in Group I. This study suggests that passive immobilisation is deleterious in respect of demineralisation of the forearm bones. PMID- 17275976 TI - Trigger wrist caused by tendon adhesion between the flexor pollicis longus and flexor digitorum superficialis tendons. PMID- 17275977 TI - -759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment. AB - 5-HT2C receptor gene is viewed as an important candidate gene in pharmacogenetic studies of antipsychotic drug-induced weight gain. However, inconsistent results have been obtained in different populations. We investigated the association between the -759C/T polymorphism of the 5-HT2C receptor gene with early phase (after 4 weeks of treatment) weight gain induced by antipsychotic treatment in Korean schizophrenia patients. The study subjects were eighty-four in-patients receiving monotherapy with one of six antipsychotic drugs. Patients with the variant allele (-759T) were found to be less likely to have substantial (> 5%) weight gain (Fisher's exact test, p=0.030), and this association (t=1.91, df=75, p=0.030) was supported by the repeated measures analysis after controlling for possible confounding effects, i.e., age, sex, baseline BMI, and the type of antipsychotic medicine administered. The variant allele also appeared to have a protective effect against weight gain in a subgroup of patients receiving risperidone. These results support the involvement of the -759C/T polymorphism of the 5-HT2C receptor gene in antipsychotics-induced weight gain in the Korean population. PMID- 17275980 TI - Applications of Botulinum toxin in urogynaecology. AB - Botulinum toxin (BTX) is a neurotoxin produced by bacterium clostridium. It is the most poisonous naturally occurring substance known to mankind. The neurotoxin binds to the peripheral cholinergic terminals and inhibits acetylcholine release at that junction leading to flaccid paralysis. This process appears to offer an attractive therapeutic option, filling the void between anticholinergics and surgery in cases of neurogenic and idiopathic detrusor overactivity, detrusor sphincter dyssynergia (DSD), interstitial cystitis and pelvic pain. This article reviews the application of Botulinum toxin A in these conditions. PMID- 17275979 TI - Affective visual event-related potentials: arousal, repetition, and time-on-task. AB - Affective stimulus pictures that differed in valence (unpleasant, neutral, and pleasant) were repeated as targets in an oddball task to elicit event-related potentials (ERPs) in young female adults. Each picture target was repeated consecutively four times, with picture order counterbalanced and time-on-task influences assessed across subjects. Response time decreased from the first to second stimulus presentation and remained stable. Stimulus repetition was associated with voltage increases for N1, P2, N2, and P3, from initial to subsequent presentations. Arousal effects did not interact with stimulus repetition at any latency range. Time-on-task was associated with decreased voltages for the N2 and P3 potentials but was unaffected by stimulus valence. The findings suggest affective arousal, stimulus repetition, and time-on-task independently modulate ERP outcomes at overlapping time ranges. Theoretical implications are discussed. PMID- 17275981 TI - Total and differential leukocyte counts percentiles in normal pregnancy. AB - OBJECTIVE: To establish leukocyte count and leukocyte differential percentiles in normal uncomplicated pregnancy. STUDY DESIGN: This retrospective longitudinal study was performed in an outpatient facility for routine antenatal care. The study population comprised of 726 healthy women from the 5th to the 41st week of pregnancy. Altogether, there were 1749 complete blood count evaluations, of which 481 were in the 1st trimester, 687 in the 2nd trimester and 581 in the 3rd trimester. The total and differential leukocyte counts were determined by an automated cell counter. RESULTS: The leukocyte and neutrophil counts gradually and significantly increased form the 1st to the 3rd trimester. The monocyte count increase became significant only during the 3rd trimester. The eosinophil count did not significantly change throughout pregnancy. The basophil count significantly decreased during the 2nd trimester and returned to 1st trimester values during the 3rd trimester. CONCLUSION: In this study, we provide total and differential leukocyte counts' mean+/-S.D., minimal and maximal values, and the 3rd, 5th, 10th, 50th, 90th, 95th, and 99th percentiles for entire pregnancy and for each trimester separately. These reference values should prove useful for diagnostic and research purposes. PMID- 17275982 TI - Size distributions of fine and ultrafine particles in the city of Strasbourg: correlation between number of particles and concentrations of NO(x) and SO(2) gases and some soluble ions concentration determination. AB - An Electrical Low Pressure Impactor (ELPI) was used during spring and autumn 2003 in the centre of Strasbourg for the measurement of atmospheric aerosols size distribution. The concentration of NO(x) and SO(2) in air was simultaneously measured with specific analysers. Samples were collected in the range 0.007-10 microm in equivalent aerodynamic diameter size. Number distributions are representative of a pollution originating from urban traffic with a particle size distribution exhibiting a nucleation mode below 29 nm and an accumulation mode around 80 nm in size. A mean particle density equal to 39000+/-35000 total particles per cm(3) with a size ranging from 7 to 10 microm was obtained after a sampling period of 2 weeks in spring. About 86.9% of the number of particles have an aerodynamic diameter below 0.1 microm and 13.1% between 0.1 and 1 microm. Correlation coefficients between the number of particles impacted on each ELPI plate and gas concentrations (SO(2) and NO(x)) showed that the numbers of particles with diameter between 0.10 and 0.62 microm are highly related to the NO(x) concentration. This result indicates that particles are traffic induced since NO(x) is mainly emitted by cars as shown by measurements on various sites. Particles are less clearly correlated to the SO(2) concentration. Particle analysis on different ELPI plates for a sampling period of 2 weeks in autumn showed high level of soluble NO(3)(-), SO(4)(2-) and NH(4)(+) ions. Indeed, up to 90% b.w. of these three species were found in the particle range 0.1-1 microm. The formation of particulate NH(4)NO(3) is favoured by high NO(x) concentration, which induces the formation of gaseous HNO(3). PMID- 17275983 TI - Objective performance testing and quality assurance of medical ultrasound equipment. AB - There is an urgent need for a measurement protocol and software analysis for objective testing of the imaging performance of medical ultrasound equipment from a user's point of view. Methods for testing of imaging performance were developed. Simple test objects were used, which have a long life expectancy. First, the elevational focus (slice thickness) of the transducer was estimated and the in-plane transmit focus was positioned at the same depth. Next, the postprocessing look-up-table (LUT) was measured and linearized. The tests performed were echo level dynamic range (dB), contrast resolution (i.e., gamma of display, number of gray levels/dB) and sensitivity, overall system sensitivity, lateral sensitivity profile, dead zone, spatial resolution and geometric conformity of display. The concept of a computational observer was used to define the lesion signal-to-noise ratio, SNR(L) (or Mahalanobis distance), as a measure for contrast sensitivity. All the measurements were made using digitized images and quantified by objective means, i.e., by image analysis. The whole performance measurement protocol, as well as the quantitative measurements, have been implemented in software. An extensive data-base browser was implemented from which analysis of the images can be started and reports generated. These reports contain all the information about the measurements, such as graphs, images and numbers. The approach of calibrating the gamma by using a linearized LUT was validated by processing simultaneously acquired rf data. The contrast resolution and echo level of the rf data had to be compressed by a factor of two and amplified by a gain factor corresponding to 12 dB. This resulted in contrast curves that were practically identical to those obtained from DICOM image data. The effects of changing the transducer center frequency on the spatial resolution and contrast sensitivity were estimated to illustrate the practical usefulness of the developed approach of quality assurance by measuring objective performance characteristics. The developed methods might be considered as a minimum set of objective quality assurance measures. This set might be used to predict clinical performance of medical ultrasound equipment, taking into account the performance at a unique point in space i.e., the coinciding depths of the elevation and in plane (azimuth) foci. Furthermore, it should be investigated whether the approach might be used to compare objectively various brands of equipment and to evaluate the performance specifications given by the manufacturer. Last but not least, the developed approach can be used to monitor, in a hospital environment, the medical ultrasound equipment during its life cycle. The software package may be viewed and downloaded at the website http://www.qa4us.eu. PMID- 17275984 TI - Lower urinary tract symptoms (LUTS) and sexual dysfunction (SD): new targets for new combination therapies? PMID- 17275985 TI - Re: Sandra Lindstedt, Ulla Lindstrom, Eva Ljunggren, Bjorn Wullt and Magnus Grabe. Single-dose antibiotic prophylaxis in core prostate biopsy: impact of timing and identification of risk factors. Eur Urol 2006;50:832-37. PMID- 17275986 TI - Re: Marzio Angelo Zullo, Francesco Plotti, Marco Calcagno, Elettra Marullo, Innocenza Palaia, Filippo Bellati, Stefano Basile, Ludovico Muzii, Roberto Angioli and Pierluigi Benedetti Panici. One-year follow-up of tension-free vaginal tape (TVT) and trans-obturator suburethral tape from inside to outside (TVT-O) for surgical treatment of female stress urinary incontinence: a prospective randomised trial. Eur Urol 2007;51:1376-84. PMID- 17275988 TI - Rebuttal from authors re: Edward M. Messing. Node positive renal cell cancer. Who can be helped? Eur Urol 2007;51:1477-8. PMID- 17275989 TI - Routine stenting after ureteroscopy: think again. PMID- 17275990 TI - Neuroimmunophilin ligands protect cavernous nerves after crush injury in the rat: new experimental paradigms. PMID- 17275991 TI - The stem cell revolution: a biologic nanotechnology. PMID- 17275978 TI - N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. AB - The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal central nervous system (CNS) development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered. PMID- 17275993 TI - Selected papers presented at the 6th International Workshop on Neural Coding, Marburg, Germany, 23-28 August 2005. PMID- 17275992 TI - Conductance versus current noise in a neuronal model for noisy subthreshold oscillations and related spike generation. AB - Biological systems are notoriously noisy. Noise, therefore, also plays an important role in many models of neural impulse generation. Noise is not only introduced for more realistic simulations but also to account for cooperative effects between noisy and nonlinear dynamics. Often, this is achieved by a simple noise term in the membrane equation (current noise). However, there are ongoing discussions whether such current noise is justified or whether rather conductance noise should be introduced because it is closer to the natural origin of noise. Therefore, we have compared the effects of current and conductance noise in a neuronal model for subthreshold oscillations and action potential generation. We did not see any significant differences in the model behavior with respect to voltage traces, tuning curves of interspike intervals, interval distributions or frequency responses when the noise strength is adjusted. These findings indicate that simple current noise can give reasonable results in neuronal simulations with regard to physiological relevant noise effects. PMID- 17275996 TI - Motor neuron disease-like syndrome secondary to trapped fourth ventricle and obstruction of cerebrospinal fluid pathway. AB - The trapped fourth ventricle is caused by occlusion of outlets of fourth ventricle, including cerebral aqueduct and foramina of Luschka and Magendie. It is an uncommon entity that mainly occurs in children with hydrocephalus after successful shunting of lateral ventricles. The most common etiologies of obstruction to outflow of the fourth ventricle are infection and hemorrhage. Typical manifestation of trapped fourth ventricle is posterior fossa syndrome. Here, we report a 22-year-old man with hydrocephalus developed after successful removal of traumatic subdural hemorrhage. After shunting of lateral ventricles, hydrocephalus resolved initially. However, trapped fourth ventricle occurred 9 months later. Unlike previous reports of trapped fourth ventricle, his presentation was motor neuron disease-like syndrome, including hand muscle weakness and atrophy, generalized brisk deep tendon reflexes, and absence of sensory deficits. Imaging study showed isolated dilatation of fourth ventricle and edema of cervical cord from obex to C7 level. After surgical decompression and lysis of adhesion of posterior fossa, neurological deficits well recovered. The pathogenesis of hand muscle atrophy is secondary to cervical cord edema caused by trapped fourth ventricle and obstruction of cerebrospinal fluid (CSF) pathway. Furthermore, the anterior horn cells and lateral corticospinal tract are located in the highly vulnerable region of spinal cord, either possibly due to venous engorgement or arterial insufficiency. PMID- 17275995 TI - Preoperative imaging of superficially located glioma resection using short inversion-time inversion recovery images in high-field magnetic resonance imaging. AB - OBJECTIVES: Short inversion-time inversion recovery (STIR) is the only magnetic resonance imaging (MRI) sequence able to produce high contrast images of both brain-CSF and gray matter-white matter in the central nervous system. The aim of the present study is to evaluate the effectiveness of STIR in imaging tumor involvement of the cortical surface and intra-axial structures, its usefulness in the resection of superficially located gliomas. PATIENTS AND METHODS: In this study, we perform conventional MRI (1.5 T) and STIR (3.0 T) before surgery in 10 patients with superficially located glioma. We estimate the spatial relationship between the tumor bulk, the adjacent cortical surface and intra-axial structures on T2WI (1.5 T) and STIR (3.0 T). STIR findings are applied to resection of the tumor in each case. RESULTS: For all patients, STIR provided more satisfactory images than T2WI of both the cortical surface structures and intra-axial structures surrounding the tumor. During surgery, the clear demonstration of cortical surface structures on preoperative STIR images assisted in determining tumor location and the sulci to be split for the trans-sulcal approach for patients whose cortex was normal in colour. Clear contrast on STIR between the tumor margin and peritumoral edema was useful for tumor resection. CONCLUSION: STIR is able to demonstrate anatomical details of the cortical surface and intra axial structures of the brain and is therefore suitable for the preoperative evaluation of superficially located gliomas. PMID- 17275994 TI - Estrogen receptor alpha regulates expression of the breast cancer 1 associated ring domain 1 (BARD1) gene through intronic DNA sequence. AB - We have used a chromatin immunoprecipitation (ChIP)-based cloning strategy to isolate and identify genes associated with estrogen receptor alpha (ERalpha) in MCF-7 human breast cancer cells. One of the gene regions isolated was a 288bp fragment from the ninth intron of the breast cancer 1 associated ring domain (BARD1) gene. We demonstrated that ERalpha associated with this region of the endogenous BARD 1 gene in MCF-7 cells, that ERalpha bound to three of five ERE half sites located in the 288bp BARD1 region, and that this 288bp BARD1 region conferred estrogen responsiveness to a heterologous promoter. Importantly, treatment of MCF-7 cells with estrogen increased BARD1 mRNA and protein levels. These findings demonstrate that ChIP cloning strategies can be utilized to successfully isolate regulatory regions that are far removed from the transcription start site and assist in identifying cis elements involved in conferring estrogen responsiveness. PMID- 17275998 TI - Connexin 43 expression promotes malignancy of HuH7 hepatocellular carcinoma cells via the inhibition of cell-cell communication. AB - In normal liver, Connexin (Cx) 43 is not detected, but up-regulated in some liver cancers. We herein investigated the role of Cx43 in hepatoma cell carcinogenesis. Cx43-silenced HuH7 cells using shRNA showed lower growth and higher differentiation, and Cx43-overexpressing cells exhibited rapid growth and low differentiation. Unexpectedly, gap junctional intercellular communication (GJIC) was inversely correlated with Cx43 levels. Furthermore, the expression level and promoter activity of Cx32 was negatively regulated by the expression of Cx43. From these data, Cx43 expression may be in part responsible for the malignancy of hepatoma cells through a decrease in GJIC composed of Cx32. PMID- 17275997 TI - Prefrontal cognitive dysfunction following brainstem lesion. AB - Prefrontal cortex (PFC) dysfunction can lead to impairment in planning and behavioral inhibition, as well as personality changes. As ascending monoaminergic brainstem systems modulate PFC functioning, it is possible that lesions in the brainstem lead to symptoms similar to prefrontal dysfunction. A 29-year-old man developed several cognitive and behavioral symptoms after neurosurgery for resection of a pilocytic astrocytoma in the pontine-mesencephalic area. A careful analysis of symptoms indicated PFC dysfunction that could be attributed to lesions in the ascending monoaminergic brainstem systems. Interestingly, the cognitive symptoms improved after treatment with methylphenidate, which is a drug that modules catecholaminergic neurotransmission, thereby supporting this hypothesis. This is a unique case of PFC dysfunction that may be related to post operative lesion of the catecholaminergic nuclei in the brainstem. PMID- 17275999 TI - Supplementation with l-carnitine does not reduce the efficacy of epirubicin treatment in breast cancer cells. AB - One of the cornerstones of therapy for invasive breast cancer includes the use of anthracyclines. Epirubicin, a stereoisomer of doxorubicin, is one of the commonly used anthracyclines. Anthracyclines while effective therapy for breast cancer, have their own unique toxicities, such as cardiomyopathy. l-Carnitine, a quarternary ammonium compound synthesized from methionine and lysine, is required for oxidative metabolism in mitochondria. Cardiac function is closely linked with oxidative metabolism whereby l-carnitine is an essential cofactor. A hypothesis is being investigated to determine if supplementation with carnitine in breast cancer patients treated with epirubicin will reduce the development of cardiac toxicity. We determined whether addition of l-carnitine altered the tumor cytotoxic effects of epirubicin using a number of in vitro cell viability assays in different breast cancer cell lines including BT549, MDA-MB-435, NCI-ADR-RES, MCF7 and T47D. Additionally we investigated the ability of cells to respond to l carnitine following analysis of the expression of carnitine metabolic enzymes by RT-PCR. We determined that supplementation with l-carnitine had no effect on the ability of epirubicin to kill a variety of breast cancer cell lines. Additionally, no differences in the induction of apoptosis by epirubicin were observed. Furthermore, all cell lines examined expressed proteins required for carnitine uptake and use. Our data suggest that supplementation with l-carnitine does not impair the ability of epirubicin to kill breast cancer cells. These results suggest that supplementation with l-carnitine in patients undergoing epirubicin treatment could be safely used to reduce associated cardiotoxicities without fear that the efficacy of chemotherapy is jeopardized. PMID- 17276000 TI - Adsorption of phenol and 4-nitrophenol on granular activated carbon in basal salt medium: equilibrium and kinetics. AB - Batch studies were carried out for studying the adsorption behaviour of phenol and 4-nitrophenol on granular activated carbon from a basal salt medium (BSM) at pH approximately 7.1 and temperature approximately 30 degrees C. The literature review was done in order to review the information for comparison purposes on equilibrium models of phenol and 4-nitrophenol adsorption on activated carbon. The units for measurements reported in these models were found to be diverse, thus making the comparison difficult. These units have been converted into similar units for easy reference. In all, six models of Freundlich, Langmuir, Redlich-Peterson, Radke-Prausnitz, Toth and Fritz-Schlunder as reported in the literature have been fitted to the data of phenol/activated carbon and 4 nitrophenol/activated carbon systems of the present studies using nonlinear regression technique. Based on maximum deviations and correlation coefficients, Langmuir gave the poorest fit for both compounds; Redlich-Peterson, Radke Prausnitz, and four parameter model of Fritz-Schlunder could represent the data with similar accuracy, i.e. with R2-value of 0.98 and maximum deviation approximately 12%. However, for phenol, two parameter model of Freundlich may be recommended because of ease in its parameter estimation and better accuracy. 4 Nitrophenol was found to be more adsorbed than phenol, which is consistent with the result found in literature. The kinetics of the adsorption was found to be intra-particle diffusion controlled with diffusion coefficient values of the order of 10(-13)m2/s. Three distinct phases of kinetics--rapid, medium, and slow- have been observed in this study. PMID- 17276001 TI - Electroosmotic flow behaviour of metal contaminated expansive soil. AB - It is important to study the flow behaviour through soil during electrokinetic extraction of contaminants to understand their removal mechanism. The flow through the expansive soil containing montmorillonite is monitored during laboratory electrokinetic extraction of heavy metal contaminants. The permeability of soil, which increases due to the presence of contaminants, is further enhanced during electrokinetic extraction of contaminants due to osmotic permeability. The variations in flow rates through the soil while the extracting fluid is changed to dilute acetic acid (used to control the increase of pH) and EDTA solution (used to desorb the metal ions from soil) are studied. The trends of removal of contaminants vis-a-vis the changes in the flow through the soil during different phases of electrokinetic extraction are established. Chromium ions are removed by flushing of water through the soil and increased osmotic flow is beneficial. Removal of iron ions is enhanced by induced osmotic flow and desorption of ions by electrokinetic processes. PMID- 17276002 TI - Effects of riluzole and flufenamic acid on eupnea and gasping of neonatal mice in vivo. AB - The pre-Botzinger complex (PBC), part of the ventral respiratory group that is responsible for inspiratory rhythm generation, contains at least two types of pacemaker neurons. In vitro studies have shown that bursting properties of one type of pacemaker relies on a riluzole-sensitive persistent sodium current, whereas bursting of a second type is sensitive to flufenamic acid (FFA), a calcium-dependent nonspecific cationic current blocker. In vitro, under control conditions, the PBC generates fictive eupneic activity that depends on both riluzole-sensitive and FFA-sensitive pacemaker neurons. During hypoxia the PBC generates fictive gasping activity and only riluzole-sensitive pacemaker neurons appear to be necessary for this rhythm. We carried out pharmacological experiments to test the role of respiratory pacemaker neurons in vivo by performing plethysmographic recordings on neonate mice. As reported in vitro, eupnea activity in vivo is abolished only if both FFA and riluzole are coadministered intracisternally, but not when either of them is administered independently. On the other hand riluzole, but not FFA, drastically reduced gasping generation and compromised the ability of mice to autoresucitate. Neither substance P nor forskolin was able to reestablish respiratory activity after riluzole and FFA coapplication. Our results confirm in vitro reports and suggest that eupnea generation in neonates requires a complex neuronal network that includes riluzole- and FFA-sensitive elements and that gasping activity depends mostly on a riluzole-sensitive mechanism. PMID- 17276003 TI - Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer's disease. AB - Alterations in signal transduction pathway of G-protein-coupled receptors (GPCRs) have been found in the cerebrocortex and in the peripheral cultured tissues of patients with Alzheimer's disease (AD). The G-protein-coupled receptor kinase-2 (GRK2) plays an important role in regulating the GPCRs signaling: its increased expression is associated with receptor desensitization. The aim of this study was to explore GRK2 levels in peripheral lymphocytes of AD patients and to establish a correlation between lymphocyte protein concentrations and the degree of cognitive impairment. GRK2 mRNA and protein expression were evaluated in the lymphocytes of AD patients with mild or moderate/severe cognitive impairment and in age-matched healthy subjects. Both GRK2 mRNA and protein expression were higher in AD patients lymphocytes compared to controls. Furthermore, lymphocyte GRK2 levels were significantly correlated to the degree of cognitive decline. Our preliminary data suggest that GRK2 is involved in GPCRs coupling dysfunction observed in AD patients. Further studies are needed in order to verify whether the lymphocyte GRK2 might be utilized as a novel biomarker in AD diagnosis and clinical monitoring. PMID- 17276004 TI - Facilitation of the soleus stretch reflex induced by electrical excitation of plantar cutaneous afferents located around the heel. AB - Previous studies have demonstrated that plantar cutaneous afferents can adjust motoneuronal excitability, which may contribute significantly to the control of human posture and locomotion. However, the role of plantar cutaneous afferents with respect to their location specificity in modulating the mechanically induced stretch reflex still remains unclear. In the present study, it was hypothesized that electrical stimulation of the ipsilateral heel region of the foot is followed by a modulation of spinal excitability, leading to a facilitation of the soleus motor output. The study was performed to investigate the effect of excitation of plantar cutaneous afferents located around the heel on the soleus stretch reflex. The soleus stretch reflex was evoked by rotating the ankle joint in dorsiflexion direction at two different angular velocities of 50 and 200 degrees s(-1). A conditioning pulse train of non-noxious electrical stimulation was delivered to the plantar surface of the heel at different conditioning test intervals ranging from 5 to 100 ms. Excitation of plantar cutaneous afferents around the heel resulted in a pronounced facilitation of the soleus stretch reflex with magnitude and time course comparable for both velocities. This facilitation was manifested by a significant increase of reflex size for conditioning test intervals from 30 to 70 ms. The observed effect implies a potential functional role of cutaneous afferents in balance control conditions where the ankle is naturally disturbed, e.g., during step reactions to external perturbations. PMID- 17276005 TI - Neuropeptide Y acts at Y1 receptors in the rostral ventral medulla to inhibit neuropathic pain. AB - Brain microinjection studies in the rat using local anesthetics suggest that the rostral ventral medulla (RVM) contributes to the facilitation of neuropathic pain. However, these studies were restricted to a single model of neuropathic pain (the spinal nerve ligation model) and to just two stimulus modalities (non noxious tactile stimulus and heat). Also, few neurotransmitter systems have been shown to modulate descending facilitation. After either partial sciatic nerve ligation (PSNL) or spared nerve injury (SNI), we found that unilateral or bilateral microinjection of lidocaine into the RVM reduced not only mechanical allodynia (decreased threshold to von Frey hairs and/or an automated device) and mechanical hyperalgesia (increased paw lifting in response to a noxious pin), but also cold hypersensitivity (increased lifting in response to the hindpaw application of a drop of acetone). Application of a drop of water did not elicit paw withdrawal, indicating that the acetone test is indeed a measure of cold hypersensitivity. We found significant neuropeptide Y Y1-like immunoreactivity within, and lateral to, the midline RVM. Intra-RVM injection of neuropeptide Y (NPY) dose-dependently inhibited the mechanical and cold hypersensitivity associated with PSNL or SNI, an effect that could be blocked by the Y1 receptor antagonist BIBO 3304. We conclude that medullary facilitation spans multiple behavioral signs of allodynia and hyperalgesia in multiple models of neuropathic pain. Furthermore, NPY inhibits behavioral signs of neuropathic pain, possibly by acting at Y1 receptors in the RVM. PMID- 17276006 TI - Choice of external criteria in back pain research: Does it matter? Recommendations based on analysis of responsiveness. AB - Understanding a change score is indispensable for interpretation of results from clinical studies. One way of determining the relevance of change scores is through the use of transition questions that assesses patients' retrospective perception of treatment effect. Unfortunately, results from studies using transition questions are difficult to compare since wording of questions and definitions of important improvements vary between studies. The objectives of this study were to determine the consequence of using different transition questions on pain and disability measures and make proposals for a standardised use of such questions. Two hundred and thirty-three patients with low back pain and/or leg pain were recruited. Participants were followed over an 8-week period and randomised to two groups receiving a 7- (TQ1) and 15-point (TQ2) transition question, respectively, in addition to a numeric rating scale evaluating the importance of the perceived change. Four external criteria were generated using both stringent and less stringent standards to dichotomise patients. Discrimination was determined using area under the receiver operating characteristic curve (ROC(auc)) and responsiveness using standardised response mean (SRM). Results demonstrated small variations in ROC(auc) across the external criteria for all outcome measures. 7% more patients were classified as improved in the group receiving the 15-point TQ compared to the 7-point TQ (stringent standard). SRMs were higher for the retrospective TQs in primary sector patients compared to the serial measures with no difference between TQ1 and TQ2. On the basis of our findings we have outlined a proposal for a standardised use of transition questions. PMID- 17276007 TI - Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: increased expression of ATF-3 and pharmacological characterisation. AB - Intra-articular injection of mono-iodoacetate (MIA) in the rat knee joint induces a histopathology with similarities to osteoarthritis (OA). Typically, a synovitis (days 1-3) is observed followed by thinning of articular cartilage and subsequent lesion of subchondral bone at days 8-14 onwards. Behaviourally, weight-bearing asymmetry is observed, which is sensitive to anti-inflammatory pharmacology at early but not later (days 14+) time points. As subchondral bone is densely innervated, an intriguing possibility is that focal bone pathology may cause neuropathy in this model. In male Wistar rats, activating transcription factor (ATF)-3-immunofluorescence was used as a marker of nerve injury in lumber (L)4 and L5 dorsal root ganglia of the ipsilateral knee. Significantly increased ATF-3 immunoreactivity following MIA treatment was measured in L5 on days 8 and 14 (P<0.05, Kruskal-Wallis and Mann-Whitney U-test), compared to saline controls. Furthermore, in an additional study animals were orally dosed vehicle (5 ml/kg), naproxen (0.3-10 mg/kg), celecoxib (1-10 mg/kg), amitriptyline (3-30 mg/kg) and gabapentin (10-100mg/kg) and evaluated for weight-bearing asymmetry on days 14, 21 and 28 post-MIA. Significant resolution of weight-bearing was observed at high and intermediate doses of amitriptyline and gabapentin at all time points (P<0.05, ANOVA, post-hoc Bonferroni's, vs pre-dose measurements). Transient and weak effects were observed with naproxen (10mg/kg) on days 14 and 28, whereas celecoxib showed no significant effects. Collectively, these data suggest that this putative model of OA is associated with an early phase neuropathy in the L5 innervation territory of the knee. PMID- 17276008 TI - Comment on Koltzenburg et al.: Differential sensitivity of three experimental pain models in detecting the analgesic effects of transdermal fentanyl and buprenorphine. Pain 2006;126:165-74. PMID- 17276009 TI - Targeting potential and anti-HIV activity of lamivudine loaded mannosylated poly (propyleneimine) dendrimer. AB - T-lymphocytes, dendritic cells and macrophages are the target cells for HIV. The infected macrophages are considered as reservoirs for spreading the virus. Treatment of HIV infection therefore must reach these cells in addition to the organs like brain, liver and bone marrow. Lectin receptors, which act as molecular targets for sugar molecules, are found on the surface of these cells of the phagocytic system. The purpose of the present study is to investigate the targeting potential and anti HIV activity of lamivudine (3TC) loaded mannosylated fifth generation Poly (propyleneimine) dendrimers (MPPI). The entrapment efficiency of 3TC loaded MPPI and 5th generation poly(propyleneimine) dendrimer (PPI) were found to be 43.27+/-0.13% and 35.69+/-0.2% respectively. The in vitro drug release profile shows that while PPI releases the drug by 24 h, the MPPI slows down and hence prolongs the release up to 144 h (96.89+/-1.8% in case of MPPI). The results of in vitro ligand agglutination assay indicated that even after conjugation with PPI, mannose displayed binding specificity towards Con A. The subtoxic concentrations of free 3TC, blank PPI, blank MPPI, drug loaded PPI and drug loaded MPPI, determined on MT2 cells, were found to be 0.625, 0.039, 0.156, 0.039 and 0.156 nM/ml respectively. Significant increase in cellular uptake of 3TC was observed when MPPI was used, which was 21 and 8.3 times higher than that of free drug (p<0.001) and PPI (p<0.001) at 48 h respectively. Antiretroviral activity was determined using MT2 cell lines by estimating p24 antigen by ELISA. 3TC loaded PPI and MPPI formulations were found to possess higher anti-HIV activity at a concentration as low as 0.019 nM/ml, as compared to that of free drug, which was found to be extremely significant (p<0.001). The significantly higher anti-HIV activity of PPI and MPPI is due to the enhanced cellular uptake of 3TC in formulation as compared to that of free drug Results suggest that the proposed carrier hold potential to increase the efficacy and reduce the toxicity of antiretroviral therapy. PMID- 17276010 TI - Inhibition of PTEN and activation of Akt by menadione. AB - Menadione (vitamin K(3)) has been shown to activate Erk in several cell lines. This effect has been shown to be due to the activation of EGF receptors (EGFR) as a result of inhibition of some protein tyrosine phosphatases. In the present study, we examined the effects of menadione on Akt in Chinese hamster ovary cells. The phosphorylation of Akt by menadione was not inhibited by AG1478, an inhibitor of EGFR. Menadione inhibited the lipid phosphatase activity of PTEN in a cell-free system. In an intact cell system, menadione inhibited the effect of transfected PTEN on Akt. Thus, one mechanism of its action was considered the accelerated activation of Akt through inhibition of PTEN. This was not the sole mechanism responsible for the EGFR-independent activation of Akt, because menadione attenuated the rate of Akt dephosphorylation even in PTEN-null PC3 cells. The decelerated inactivation of Akt, probably through inhibition of some tyrosine phosphatases, was considered another mechanism of its action. PMID- 17276013 TI - Auditory responses in the visual cortex of neonatally enucleated rats. AB - A number of studies on humans and animals have demonstrated better auditory abilities in blind with respect to sighted subjects and have tried to define the mechanisms through which this compensation occurs. The aim of the present study, therefore, was to examine the participation of primary visual cortex (V1) to auditory processing in early enucleated rats. Here we show, using gaussian noise bursts, that about a third of the cells in V1 responded to auditory stimulation in blind rats and most of these (78%) had ON-type responses and low spontaneous activity. Moreover, they were distributed throughout visual cortex without any apparent tonotopic organization. Optimal frequencies determined using pure tones were rather high but comparable to those found in auditory cortex of blind and sighted rats. On the other hand, sensory thresholds determined at these frequencies were higher and bandwidths were wider in V1 of the blind animals. Blind and sighted rats were also stimulated for 60 min with gaussian noise, their brains removed and processed for c-Fos immunohistochemistry. Results revealed that c-Fos positive cells were not only present in auditory cortex of both groups of rats but there was a 10-fold increase in labeled cells in V1 and a fivefold increase in secondary visual cortex (V2) of early enucleated rats in comparisons to sighted ones. Also, the pattern of distribution of these labeled cells across layers suggests that the recruitment of V1 could originate at least in part through inputs arising from the thalamus. The ensemble of results appears to indicate that cross-modal compensation leading to improved performance in the blind depends on cell recruitment in V1 but probably also plastic changes in lower- and higher-order visual structures and possibly in the auditory system. PMID- 17276012 TI - Environmental lead exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats. AB - Exposure to environmentally relevant levels of lead (Pb(2+)) during early life produces deficits in hippocampal synaptic plasticity in the form of long-term potentiation (LTP) and spatial learning in young adult rats [Nihei MK, Desmond NL, McGlothan JL, Kuhlmann AC, Guilarte TR (2000) N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficits of long-term potentiation and spatial learning. Neuroscience 99:233-242; Guilarte TR, Toscano CD, McGlothan JL, Weaver SA (2003) Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol 53:50 56]. Other evidence suggests that the performance of rats in the Morris water maze spatial learning tasks is associated with the level of granule cell neurogenesis in the dentate gyrus (DG) [Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza P-V, Abrous DN (2003) Spatial memory performance of aged rats in the water maze predicts level of hippocampal neurogenesis. Proc Natl Acad Sci U S A 100:14385-14390]. In this study, we examined whether continuous exposure to environmentally relevant levels of Pb(2+) during early life altered granule cell neurogenesis and morphology in the rat hippocampus. Control and Pb(2+)-exposed rats received bromodeoxyuridine (BrdU) injections (100 mg/kg; i.p.) for five consecutive days starting at postnatal day 45 and were killed either 1 day or 4 weeks after the last injection. The total number of newborn cells in the DG of Pb(2+)-exposed rats was significantly decreased (13%; P<0.001) 1 day after BrdU injections relative to controls. Further, the survival of newborn cells in Pb(2+) exposed rats was significantly decreased by 22.7% (P<0.001) relative to control animals. Co-localization of BrdU with neuronal or astrocytic markers did not reveal a significant effect of Pb(2+) exposure on cellular fate. In Pb(2+) exposed rats, immature granule cells immunolabeled with doublecortin (DCX) displayed aberrant dendritic morphology. That is, the overall length-density of the DCX-positive apical dendrites in the outer portion of the DG molecular layer was significantly reduced up to 36% in the suprapyramidal blade only. We also found that the area of Timm's-positive staining representative of the mossy fibers terminal fields in the CA3 stratum oriens (SO) was reduced by 26% in Pb(2+)-exposed rats. These findings demonstrate that exposure to environmentally relevant levels of Pb(2+) during early life alters granule cell neurogenesis and morphology in the rat hippocampus. They provide a cellular and morphological basis for the deficits in synaptic plasticity and spatial learning documented in Pb(2+)-exposed animals. PMID- 17276011 TI - Fos and glutamate AMPA receptor subunit coexpression associated with cue-elicited cocaine-seeking behavior in abstinent rats. AB - Cocaine-associated cues acquire incentive motivational effects that manifest as craving in humans and cocaine-seeking behavior in rats. We have reported an increase in neuronal activation in rats, measured by Fos protein expression, in various limbic and cortical regions following exposure to cocaine-associated cues. This study examined whether the conditioned neuronal activation involves glutamate AMPA receptors by measuring coexpression of Fos and AMPA glutamate receptor subunits (GluR1, GluR2/3, or GluR4). Rats trained to self-administer cocaine subsequently underwent 22 days of abstinence, during which they were exposed daily to either the self-administration environment with presentations of the light/tone cues previously paired with cocaine infusions (Extinction group) or an alternate environment (No Extinction group). All rats were then tested for cocaine-seeking behavior (i.e. responses without cocaine reinforcement) and Fos and AMPA glutamate receptor subunits were measured postmortem using immunocytochemistry. The No Extinction group exhibited increases in cocaine seeking behavior and Fos expression in limbic and cortical regions relative to the Extinction group. A large number of Fos immunoreactive cells coexpressed GluR1, GluR2/3, and GluR4, suggesting that an action of glutamate at AMPA receptors may in part drive cue-elicited Fos expression. Importantly, there was an increase in the percentage of cells colabeled with Fos and GluR1 in the anterior cingulate and nucleus accumbens shell and cells colabeled with Fos and GluR4 in the infralimbic cortex, suggesting that within these regions, a greater, and perhaps even different, population of AMPA receptor subunit-expressing neurons is activated in rats engaged in cocaine-seeking behavior. PMID- 17276015 TI - [Management of endometriosis: clinical and biological assessment]. AB - No symptom is pathognomonic for endometriosis. Main symptoms are pain (chronic pelvic pain, dysmenorrhea, deep dyspareunia, pain on defecation, cyclic pain) and infertility (grade C). There is no relation between rAFS endometriosis classification and symptoms intensity and frequency (grade B). Endometriosic lesions location and symptoms type are related to each other as well as symptoms intensity and lesions deepness or adhesion numbers (grade B). Clinical evidence is the same for infertile endometriosic women (grade C). Screening for depression is required among patients suffering from chronic endometriosic pelvic pain (grade C). Clinical examination includes: 1) retrocervix area inspection as well as upper part of posterior vaginal wall in search for typical bluish lesions (grade B); 2) vaginal examination in search for: a) uterosacral ligaments nodules (grade B); b) pain in uterosacral ligaments extension (grade B); 3) re examination during menstruation increases its performance (grade B). No biological check-up in endometriosis diagnosis is necessary (grade A). CA 125 increase is related to: endometriomas and deep lesions volume (grade B), surgically treated infertile women prognosis (grade B). Presurgical endometriosis diagnosis is bettered by using diagnosis pattern in selected population (grade B). Rating scales are recommended in diagnosis and therapeutic follow up (grade B). Quality of life scales are useful to evaluate therapeutic efficiency (grade B). PMID- 17276014 TI - Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. AB - Patients with the rare genetic disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS) have defects in DNA nucleotide excision repair (NER). The NER pathway involves at least 28 genes. Three NER genes are also part of the basal transcription factor, TFIIH. Mutations in 11 NER genes have been associated with clinical diseases with at least eight overlapping phenotypes. The clinical features of these patients have some similarities but also have marked differences. NER is involved in protection against sunlight-induced DNA damage. While XP patients have 1000-fold increase in susceptibility to skin cancer, TTD and CS patients have normal skin cancer risk. Several of the genes involved in NER also affect somatic growth and development. Some patients have short stature and immature sexual development. TTD patients have sulfur deficient brittle hair. Progressive sensorineural deafness is an early feature of XP and CS. Many of these clinical diseases are associated with developmental delay and progressive neurological degeneration. The main neuropathology of XP is a primary neuronal degeneration. In contrast, CS and TTD patients have reduced myelination of the brain. These complex neurological abnormalities are not related to sunlight exposure but may be caused by developmental defects as well as faulty repair of DNA damage to neuronal cells induced by oxidative metabolism or other endogenous processes. PMID- 17276016 TI - [Guidelines for the management of painful endometriosis]. AB - OBJECTIVES: To establish guidelines for the medical and surgical management of painful endometriosis. MATERIAL AND METHODS: An exhaustive review on Medline and Cochrane Database between 1980 and 2006 was performed. RESULTS: GnRH agonists, progestins, continuous monophasic oral contraceptives and danazol have a suppressive effect on dysmenorrhoea, nonmenstrual pain and dyspareunia (grade A). Surgical treatment is effective in painful endometriosis (grade B). Complete surgical excision of deep endometriotic lesions with conservation of uterus and ovaries has a limited term efficacy on pain relief (grade C). A multidisciplinary approach is recommended (grade C). The use of the psychotherapy improves the management of chronic pain (grade A). There is a lack of information concerning the therapeutic strategy able to prevent recurrences. Whether endometriosis recurrences occur, medical treatment should be the first line approach (expert opinion). A hysterectomy with salpingo-oophorectomy and complete excision of the lesions is efficient in women with pain recurrence who no longer desire pregnancy (grade C). CONCLUSION: Medical and surgical treatments have a limited term efficacy on painful endometriosis (grade A). The benefit/risk relationship, depending on secondary effect therapy, should be assessed on a case to case basis. PMID- 17276017 TI - [Extragenital endometriosis]. AB - Parietal, appendiceal, pleuropulmonary and diaphragmatic endometriosis represent 5% of endometriosis cases. Diagnosis and management of these extra-genital localisations are described according to the literature. Parietal endometriosis usually requires large resection of the tumor. Appendiceal endometriosis is frequently observed in cases of digestive endometriosis. Induration or rigidity of the appendix due to the presence of deep infiltrating endometriosis justifies appendicectomy. Thoracic and diaphragmatic endometriosis is characterized by the presence of typical symptoms during the perimenstrual periode. Medical treatment obtaining therapeutic amenorrhea is firstly administered and surgery is indicated in cases of symptoms recurrence. PMID- 17276019 TI - Structure-based mutation analysis shows the importance of LRP5 beta-propeller 1 in modulating Dkk1-mediated inhibition of Wnt signaling. AB - A single point mutation (G to T) in the low-density lipoprotein receptor related protein 5 (LRP5) gene results in a glycine to valine amino acid change (G171V) and is responsible for an autosomal dominant high bone mass trait (HBM) in two independent kindreds. LRP5 acts as a co-receptor to Wnts with Frizzled family members and transduces Wnt-canonical signals which can be antagonized by LRP5 ligand, Dickkopf 1 (Dkk1). In the presence of Wnt1, LRP5 or the HBM variant (LRP5 G171V) induces beta-catenin nuclear translocation and activates T cell factor (TCF)-luciferase reporter activity. HBM variant suppresses Dkk1 function and this results in reduced inhibition of TCF activity as compared to that with LRP5. Structural analysis of LRP5 revealed that the HBM mutation lies in the 4th blade of the first beta-propeller domain. To elucidate the functional significance and consequence of the LRP5-G171V mutation in vitro, we took a structure-based approach to design 15 specific LRP5 point mutations. These included (a) substitutions at the G171 in blade 4, (b) mutations in blades 2-6 of beta propeller 1, and (c) mutations in beta-propellers 2, 3 and 4. Here we show that substitutions of glycine at 171 to K, F, I and Q also resulted in HBM-like activity in the presence of Wnt1 and Dkk1. This indicates the importance of the G171 site rather than the effect of specific amino acid modification to LRP5 receptor function. Interestingly, G171 equivalent residue mutations in other blades of beta-propeller 1 (A65V, S127V, L200V, A214V and M282V) resulted in LRP5 G171V-like block of Dkk1 function. However G171V type mutations in other beta propellers of LRP5 did not result in resistance to Dkk1 function. These results indicate the importance of LRP5 beta-propeller 1 for Dkk1 function and Wnt signaling. These data and additional comparative structural analysis of the LRP5 family member LDLR suggest a potential functional role of the first beta propeller domain through intramolecular interaction with other domains of LRP5 wherein Dkk1 can bind. Such studies may also lead to a better understanding of the mechanisms underlying the reduced function of Dkk1-like inhibitory ligands of LRP5 with HBM-like mutations and its relationship to increased bone density phenotypes. PMID- 17276018 TI - Convenience is the key to hepatitis A and B vaccination uptake among young adult injection drug users. AB - BACKGROUND: Despite CDC recommendations to vaccinate injection drug users (IDUs) against hepatitis A virus (HAV) and hepatitis B virus (HBV) infections, coverage remains low. Vaccination programs convenient to IDUs have not been widely implemented or evaluated. We assessed whether convenience and monetary incentives influenced uptake of free vaccine by 18-30-year-old IDUs in five U.S. cities. METHODS: IDUs recruited from community settings completed risk behavior self interviews and testing for antibodies to HAV (anti-HAV) and hepatitis B core antigen (anti-HBc). Vaccine was offered presumptively at pre-test (except in Chicago); on-site availability and incentives for vaccination differed by site, creating a quasi-experimental design. RESULTS: Of 3181 participants, anti-HAV and anti-HBc seroprevalence was 19% and 23%, respectively. Although 83% of participants were willing to be vaccinated, only 36% received > or =1 dose, which varied by site: Baltimore (83%), Seattle (33%), Los Angeles (18%), New York (17%), and Chicago (2%). Participation was highest when vaccine was available immediately on-site and lowest when offered only after receiving results. Monetary incentives may have increased participation when on-site vaccination was not available. CONCLUSION: IDUs were willing to be vaccinated but immediate, on site availability was critical for uptake. Convenience should be a key consideration in designing strategies to increase vaccine coverage among IDUs. PMID- 17276020 TI - Stenotrophomonas maltophilia as a part of normal oral bacterial flora in captive snakes and its susceptibility to antibiotics. AB - Only little is known about normal oral bacterial flora in captive snakes containing Stenotrophomonas maltophilia. This microbe has been reported as a causative agent of numerous infections in reptiles. Therefore, the goal of the study was to detect its presence in the mouths of a significant number of healthy captive snakes and determining its susceptibility to antibiotics at 30 and 37 degrees C. The isolates were obtained in 1999-2005 from mouth swabs of 115 snakes of 12 genera and 22 species-most often Elaphe guttata (24 individuals; 20.9%). Susceptibility to 24 antibiotics was tested by the microdilution method. The microbe was demonstrated in 34 (29.6%) individuals. Overall, 47 strains of S. maltophilia were acquired. Evaluation using PFGE profiles and antibiograms resulted in confirmation of one strain of S. maltophilia in 23 (20.0%) individuals, two strains in nine (7.8%) and three in two (1.8%) snakes. All tested antibiotics were more effective at 37 degrees C, with the partial exception of cotrimoxazole and cefoperazone/sulbactam. At a temperature of 37 degrees C, the lowest frequency of resistance to levofloxacin (no resistant strains), cotrimoxazole and ofloxacin (97.9% of susceptible strains) was recorded. At 30 degrees C, the most active agents were cotrimoxazole (97.9% of susceptible strains), levofloxacin (91.5%) and ofloxacin (85.1%). In conclusion, S. maltophilia is present in the mouths of about one third of healthy captive snakes, showing good susceptibility to cotrimoxazole, some fluoroquinolones and aminoglycosides. The antibiotics (particularly aminoglycosides) are more effective at 37 degrees C. PMID- 17276021 TI - Exploratory field study on Mycoplasma hyopneumoniae infection in suckling pigs. AB - The present study focused on Mycoplasma hyopneumoniae (M. hyopneumoniae) detection by nPCR in nasal swabs of 507 suckling pigs. These animals came from 69 sows (from 1 to 8 parity number) of a farrow-to-finish herd with Enzootic Pneumonia (EP) problems at finishing stages. At 1 and 3 weeks of age (still in the farrowing units), nasal swabs and blood samples were taken from all piglets. Moreover, from these 507 animals, 37 randomly selected pigs were necropsied at 3 weeks of age. From those necropsied pigs, M. hyopneumoniae presence was tested in bronchial and tonsillar swabs. At 1 week post-farrowing, blood samples from sows were collected and used to detect M. hyopneumoniae antibodies. From the 69 analysed sows, 19 (27.5%) were seropositive. Global percentage of pigs with M. hyopneumoniae detection in nasal swabs at 1 and 3 weeks of age was 1.5% (8 out of 507) and 3.8% (19 out of 507), respectively. From these nPCR positive pigs, 89% (24 out of 27) were seronegative and 11% were seropositive. From necropsied animals, the pathogen DNA was detected in two pigs at bronchus level and in another pig at tonsil. In this study, sow parity was not statistically related with sow seropositivity and piglet colonization. These results confirm that M. hyopneumoniae infection may be detected not only in nasal cavities of naturally infected suckling piglets but also at their low respiratory tract airways. Our results suggest that M. hyopneumoniae detection in lower and upper respiratory tract could be an indicator that respiratory problems associated to EP may start relatively early in the production system. In consequence, sow-to-piglet and/or piglet-to piglet transmission in farrowing barns should not be underestimated. PMID- 17276022 TI - Protective and immunomodulatory effect of Gingyo-san in a murine model of acute lung inflammation. AB - To investigate the effects of Gingyo-san (GGS), the traditional Chinese medicinal formula, on the acute lung inflammation induced by LPS in vivo, mice were challenged with intratracheal LPS before treatment with GGS or vehicle. In lung morphology, GGS reduced the infiltration of activated polymorphonuclear neutrophils in the airways, decreased pulmonary edema, reduced nitrosative stress, and improved lung morphology. ELISA or RT-PCR detected the expression of cytokines in BALF and lung tissue. The mechanism of these benefits by treatment with GGS including attenuating expression TNFalpha, IL-1 beta, IL-6, KC, MCP-1, MIP-2, iNOS, and activation of nuclear factor (NF-kappaB and AP-1) in BALF and lung tissue. Particularly, GGS also enhanced the anti-inflammatory cytokine (IL 10) and limited the acute lung inflammation. Therefore, its protection activity against LPS-induced lung inflammatory mediators release might be beneficial in the treatment of endotoxin-associated inflammation. PMID- 17276023 TI - A preliminary investigation into the use of biosensors to screen stomach contents for selected poisons and drugs. AB - The bioluminescence response of two genetically modified (lux-marked) bacteria to potentially toxic compounds (PTCs) in stomach contents was monitored using an in vitro assay. Cells of Escherichia coli HB101 and Salmonella typhimurium both carrying the lux light producing gene on a plasmid (pUDC607) were added to stomach contents containing various concentrations of organic and inorganic compounds. There was some variability in the response of the two biosensors, but both were sensitive to the herbicides glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T); pentachlorophenol (PCP), and inorganic poisons arsenic and mercury at a concentration range likely to be found in stomach contents samples submitted for toxicological analysis. This study demonstrates that biosensor bioassays could be a useful preliminary screening tool in forensic toxicology and that such a toxicological screening should include more than one test organism to maximise the number of PTC's detected. The probability of false positive results from samples containing compounds that may interfere with the assay such as over-the-counter (OTC) drugs and caffeine in tea and coffee was also investigated. Of the substances tested only coffee has the potential to cause false positive results. PMID- 17276024 TI - Massive cholesteatoma of the frontal sinus: case report and review of the literature. AB - A case of a massive cholesteatoma of the frontal sinus in an 80-year-old female is reported. This lesion is very uncommon and a review of the English literature revealed only 12 reported cases. Characteristically, these tumors present unilaterally as a painless, slow-growing mass, often accompanied by frontal headache, proptosis and diplopia, and without a history of frontal sinus infection. Curative treatment includes total excision of the cholesteatoma with adequate drainage, which leaves the patient with an excellent prognosis although late recurrence has been reported. While this type of lesion is very rare, it is nevertheless an important differential diagnosis of frontal sinus tumors, due to the associated destruction of bone. PMID- 17276025 TI - Mesoflavibacter zeaxanthinifaciens gen. nov., sp. nov., a novel zeaxanthin producing marine bacterium of the family Flavobacteriaceae. AB - A novel strictly aerobic, gliding, Gram-negative, rod-shaped, halo- and mesophilic bacterium (TD-ZX30(T)) was isolated from a seawater sample collected on the Pacific coastline of Japan near Kamakura City (Fujisawa, Kanagawa). The temperature range for growth of TD-ZX30(T) was between 16 and 44 degrees C. The DNA G+C content was 32.0mol%. The predominant fatty acids were iso-C(15:1) G, iso C(15:0), iso-C(16:0) 3-OH, iso-C(15:0) 3-OH, Summed feature (iso-C(15:0) 2-OH and/or C(16:1)omega7c), iso-C(17:0) 3-OH, and C(15:0). MK-6 was the only respiratory quinone. Zeaxanthin was the major carotenoid pigment produced but flexirubin-type pigments were not produced. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that TD-ZX30(T) belonged to a distinct lineage in the family Flavobacteriaceae, sharing 93.9% sequence similarity with the nearest species Olleya marilimosa. TD-ZX30(T) could be distinguished from the other members of the family Flavobacteriaceae by a number of chemotaxonomic and phenotypic characteristics. The results of polyphasic taxonomic analyses suggested that TD-ZX30(T) represents a novel genus and a novel species, for which the name Mesoflavibacter zeaxanthinifaciens gen. nov., sp. nov. is proposed. The type strain is TD-ZX30(T) (=NBRC 102119=CCUG 53614=DSM 18436). PMID- 17276026 TI - [Evidence-based medicine: methods and critics]. AB - The evaluation of professional practices is now obligatory. Evidence-Based Medicine, defined as the use of current best evidence in making well-informed decisions, could play a major role for that purpose, as it allows an objective evaluation of the clinical practices by the use of there commendations it gives rise to. The aim of that study was to describe the EBM decision procedure with examples in anaesthesia, and to present its limits, particularly due to the problems of hierarchies of evidence. PMID- 17276027 TI - [Evaluation of a training method for transtracheal punction for emergency oxygenation]. AB - INTRODUCTION: Transtracheal oxygenation is a lifesaving technique in a cannot ventilate, cannot-intubate situation, in setting percutaneous transtracheal catheter. OBJECTIVE: To assess training for cricoid membrane puncture performed with a Ravussin needle. METHOD: Ten residents in anaesthesiology nearing completion of their training participated in the study. Following a didactic session and a video demonstration, participants performed percutaneous transtracheal punctures on fresh cadavers. Success rate and time to perform the puncture were measured. Results are expressed as mean+/-SD. RESULTS: By the third attempt, all procedures were successful. Mean performance time at the first attempt was 31.2+/-21.8 s, progressively decreasing with the following attempts to reach a plateau by the third attempt (20.6+/-19.3s). Performance time varies with the cadaver's morphology and the ability to recognize anatomic landmarks. However, whatever the difficulty, performance time is 40 s or less by the third attempt. CONCLUSION: Percutaneous transtracheal catheter setting is a life saving technique with which every anaesthesiologist should be familiar. Viewing a pedagogic videotape and training on cadavers provides a rapid and effective training method for cricoid membrane puncture. Four attempts seem necessary to obtain an optimal success rate. PMID- 17276028 TI - [Venous gas embolism from pleurovenous fistula]. AB - We report the case of an iatrogenic gas embolism related to a subclavian vein catheterization complicated by a preexisting partial pneumothorax. Catheterization was indicated because of a septic shock due to nosocomial pneumonia. Five days after the catheterization, the haemodynamics and gas exchanges of the patient worsened. A transthoracic echography showed gas embolism in the right heart related to a right partial pneumothorax. A leak between the pleura and the left subclavian vein was diagnosed. The insertion of a chest tube stopped the airflow, by suppressing the pneumothorax. PMID- 17276029 TI - [Non-guideline use of innovative and expensive drugs in pediatrics: assessing clinical practice]. AB - OBJECTIVE: The objective of this study was to analyze in a pediatric hospital the use of expensive drugs as part of the new activity-based system (T2A) of funding for French public hospitals. We identified and analyzed the therapeutic use of these drugs in indications not included in the expert recommendations issued to accompany this change, with the goal of proposing specific pediatric recommendations. METHOD: Analysis of prescriptions from May through September 2005 showed that 259 patients received expensive drugs subject to special reimbursement. The computerized prescription system enabled us to monitor and validate prescriptions daily. Indications for these expensive drugs were ranked by relevance. RESULTS: The prescriptions analyzed covered 26 expensive drugs. Among the 344 "patient-drugs", 80% were expensive drugs for an accepted therapeutic use, 5% for a pertinent therapeutic use (under evaluation), and 15% for "off-label" uses (2% "not approved" and 13% for indications not considered by the recommendations). CONCLUSION: This study showed that some therapeutic uses not approved by the official recommendations are nevertheless justified. Gathering data from other pediatric hospitals is essential to determine the need for pediatric clinical trials. PMID- 17276030 TI - ANAM genogram: historical perspectives, description, and current endeavors. AB - This paper presents a historical overview and current perspective of the Automated Neuropsychological Assessment Metrics (ANAM) test system. We discuss the history of its development along with a synopsis of the evolution of computerized testing that has occurred and led to ANAM over the past 30 years within the Department of Defense (DoD). We include a description of our current system and test library. Finally, we present an overview of advanced development projects that are presently underway. We have intentionally avoided addressing issues of reliability, stability, clinical sensitivity, and construct validity in this paper. These issues are presented in other reports in this special issue. PMID- 17276031 TI - Predicting children's anxiety from early attachment relationships. AB - This study assessed whether infants with anxious-ambivalent attachment develop higher levels of anxiety later in childhood than do infants with secure attachment. Infants (N=136) participated in Ainsworth's Strange Situation Procedure at 12 months of age. The Screen for Child Anxiety Related Emotional Disorders (SCARED) was completed by children and their mothers at 11 years of age. Results show that compared with children who were securely attached in infancy, children who were ambivalently attached had higher levels of school phobia, and, that compared with boys who were securely attached boys who were ambivalently attached had higher levels of social phobia at 11 years. However, in this normative sample, anxious-ambivalent attachment was not related to anxiety levels that approach pathological significance. These findings are discussed within the context of previous research on associations between attachment and anxiety disorders. PMID- 17276032 TI - Support for the predictive validity of the SASC-R: linkages with reactions to an in vivo peer evaluation manipulation. AB - The present study examined the predictive validity of the Social Anxiety Scale for Children-Revised (SASC-R) by investigating associations between children's social anxiety symptoms and their cognitive and behavioral reactions in response to an in vivo peer evaluation manipulation. Participants (N=115) ages 10-13, played a computer game based on the television show Survivor and were randomized to either a peer rejection (i.e., receiving the lowest total 'likeability' score from a group of peer-judges), a peer success (i.e., receiving the highest score), or a neutral peer feedback condition. Children reporting higher levels of social anxiety displayed more negative game-relevant performance expectations as well as more negative cognitive evaluations of both success and failure feedback. Moreover, regardless of feedback valence, children scoring higher on social anxiety reported greater reluctance to engage in game-related social activities. These findings provide support for the predictive validity of the SASC-R. PMID- 17276033 TI - Comparative immunohistochemical study of the dopaminergic systems in two inbred mouse strains (C57BL/6J and DBA/2J). AB - This study investigated possible neurochemical differences in the brain of two inbred mouse strains, C57BL/6J (C57) and DBA/2J (DBA) that in behavioral, memorization and learning tasks under normal and experimental conditions perform differently or often in an opposite manner. The immunohistochemical study, designed to investigate the dopaminergic system, identified many differences within the midbrain A10 area and less marked differences in areas A9 and A8. The number of dopamine transporter (DAT), vesicular monoamine transporter of type 2 (VMT) and tyrosine hydroxylase (TH) immunoreactive cell bodies was significantly higher in the midbrain of DBA mice than in C57 mice (on average +21.5%, P<0.001 in A10: +9.4% in A9, P<0.05: and +5.9% in A8, P<0.1). The distribution patterns of nerve fibres immunoreactive for same antisera also differed significantly in the two strains, especially at prelimbic, infralimbic and anterior cingulate cortical levels. In C57 mice these fibres were scanty whereas in DBA mice they were well represented. In the nucleus accumbens, also the territorial distribution of DAT immunoreactive nerve fibres differed in the two strains. In the midbrain, the galanin immunoreactive axons were more densely distributed in DBA than in C57 mice whereas neurotensin immunoreactive axons were more densely distributed in C57 than in DBA. These distinct immunohistochemical patterns could help to explain why performance differs in the two mouse strains. PMID- 17276035 TI - Lower red blood cell folate enhances the HPV-16-associated risk of cervical intraepithelial neoplasia. AB - OBJECTIVE: We previously reported that higher circulating concentrations of folate are independently associated with a lower likelihood of becoming positive for high-risk human papillomaviruses (HR-HPVs) and of having a persistent HR-HPV infection and a greater likelihood of becoming HR-HPV negative (Cancer Res 2004;64:8788-93). In the present study conducted in the same study population, we tested whether circulating folate concentrations modify the risk of cervical intraepithelial neoplasia (CIN) > or =2 associated with specific types of HR-HPV. METHODS: Multiple logistic regression models were used to assess associations (odds ratio with 95% confidence intervals) across HR-HPV, folate, and rigorously reviewed cervical histology of each subject. RESULTS: HPV-16-positive women with low red blood cell folate were significantly more likely to be diagnosed with CIN > or =2 than were HPV-16-negative women with higher red blood cell folate (odds ratio 9, 95% confidence interval 3.3-24.8). CONCLUSION: To our knowledge, this is the first study reporting an independent association of folate with risk of having CIN > or =2 in a population tested extensively for HR-HPV and CIN that also adequately controlled for several other micronutrients and known risk factors for CIN. Our findings suggest that improving the folate status in HR-HPV infected women may reduce the risk of CIN and thus the risk of cervical cancer. Folate supplementation should be tested as a means of reducing the risk of developing CIN > or =2 in women exposed to HR-HPV, especially HPV-16. PMID- 17276036 TI - High glycine levels are associated with prepulse inhibition deficits in chronic schizophrenia patients. AB - Prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating, is decreased in schizophrenia. The validity of a glutamatergic, N-methyl d-aspartate receptor (NMDAR)-mediated model of PPI disruption is presently equivocal. The NMDAR antagonist ketamine disrupts PPI in rodents, but may increase PPI in healthy volunteers. Glycine (GLY), which acts as an obligatory co agonist at the NMDAR-GLY site, induces PPI deficits in rats although, consistent with the hypo-NMDAR hypothesis, improves negative and cognitive symptoms in schizophrenia patients. We assessed the hypothesis that GLY serum levels may affect PPI parameters in schizophrenia. Forty-five chronically ill medicated schizophrenia patients and 37 matched healthy comparison subjects were tested for PPI of the eyeblink component of the startle reflex measured by electromyogram recording. Patients' demographic variables, symptom severity scores and GLY, serine and glutamate serum levels were obtained. Patients showed deficient PPI in blocks two and three of the PPI session and differed from controls in terms of change of degree of PPI as a function of the prepulse to eliciting stimulus interval. GLY levels correlated negatively with PPI parameters, such that patients with the highest GLY levels showed decreased PPI (rs=-0.4, p=0.03). These preliminary findings indirectly support previous observations on ketamine effects upon PPI in humans and suggest a dissociation of symptomatology and PPI changes as function of NMDAR modulation in schizophrenia. PMID- 17276034 TI - Ankyrin repeat and SOCS box containing protein 4 (Asb-4) interacts with GPS1 (CSN1) and inhibits c-Jun NH2-terminal kinase activity. AB - Asb-4 is a gene that is specifically expressed in the hypothalamic energy homeostasis-associated areas and is down-regulated in the arcuate nucleus of fasted Sprague Dawley and obese Zucker rats. It has two functional domains, the ankyrin repeat and the SOCS box. The function of Asb-4 is unclear. We used yeast two hybridization to search for protein(s) that interact with Asb-4. With Asb-4 minus its SOCS box (Asb-4/Deltasb) as a bait, we screened mouse testis and arcuate nucleus cDNA libraries and identified G-protein pathway suppressor 1 (GPS1, also known as CSN1) as an Asb-4 interacting protein. GPS1 co immunoprecipitated with Asb-4 both in vitro and in human HEK293 cells. When Asb-4 and GPS1 were co-transfected into HEK293 cells, expression of Asb-4 reduced the protein level of GPS1. Deletion of the SOCS box (Asb4/Deltasb) did not abolish the inhibitory effect of Asb-4 on GPS1, indicating that the SOCS box was not needed for its inhibitory effect. In NIH 3T3 L1 cells, expression of GPS1 enhanced c-Jun NH2-terminal kinase (JNK) activity. Co-expression of Asb-4 with GPS1 inhibited JNK activity. Treatment of the cells with insulin (20 nM) stimulated JNK activity. Expression of GPS1 potentiated the stimulatory effect of insulin, whereas co-expression of Asb-4 along with GPS1 inhibited JNK activity. In HEK293 cells expression of GPS1 elevated phosphorylation of insulin receptor substrate 1 (IRS-1) at serine307, co-expression of Asb-4 with GPS1 reduced the IRS-1ser307 phosphorylation. The present study demonstrates that Asb-4 interacts with GPS1 and inhibits JNK activity. PMID- 17276037 TI - Prolonged exposure of methicillin-resistant Staphylococcus aureus (MRSA) COL strain to increasing concentrations of oxacillin results in a multidrug-resistant phenotype. AB - Our previous studies demonstrated that exposure of a bacterium to increasing concentrations of an antibiotic would increase resistance to that antibiotic as a consequence of activating efflux pumps. This study utilises the same approach; however, it employs the methicillin-resistant Staphylococcus aureus (MRSA) COL strain, which is highly resistant to oxacillin (OXA). MRSA COL was adapted to 3200 mg/L of OXA. Changes in resistance to other antibiotics were evaluated and efflux pump activity during the adaptation process was determined. MRSA COL was exposed to stepwise two-fold increases of OXA. At the end of each step, minimum inhibitory concentration determination for erythromycin (ERY) and other antibiotics was conducted. Reserpine (RES) was employed to evaluate whether resistance to ERY was dependent on efflux pump activity. Efflux pump activity was also evaluated using the ethidium bromide (EB) assay. DNA typing of the products of each culture step was conducted to assess purity. Serial exposure of MRSA COL to increasing concentrations of OXA resulted in increased resistance to ERY, which could be eliminated with RES. Evaluation of efflux pump activity by the EB method indicated increased efflux activity. Resistance to ERY was accompanied by resistance to kanamycin, amikacin, ofloxacin, norfloxacin, ciprofloxacin and rifampicin. This is the first time that a multidrug-resistant phenotype has been experimentally produced as a consequence of exposure of the organism to an antibiotic to which it is initially highly resistant. PMID- 17276038 TI - Nosocomial outbreak of genetically related IMP-1 beta-lactamase-producing Klebsiella pneumoniae in a general hospital in Japan. AB - Gram-negative bacteria with acquired metallo-beta-lactamase (MBL) resistance are being increasingly described worldwide. Here we report the first case of an outbreak by a cluster of genetically related strains of Klebsiella pneumoniae producing the IMP-1 MBL. Six isolates of K. pneumoniae with a ceftazidime minimum inhibitory concentration >/=64 microg/mL were collected between February 2003 and June 2004 in Hanyu General Hospital, Saitama, Japan. These isolates were analysed to establish the mechanism of resistance. The zone of inhibition of these isolates using ceftazidime or imipenem disks on Mueller-Hinton agar containing dipicolinic acid was much larger than on Mueller-Hinton agar without dipicolinic acid. Polymerase chain reaction and DNA sequencing confirmed that the isolates contained bla(IMP-1) as well as intI1 as a class I integrase gene. Pulsed-field gel electrophoresis was performed, showing that five of the six isolates were related. This outbreak was controlled by restrained and careful use of antibiotics as well as strict hygiene practices. PMID- 17276039 TI - Differential expression of bla(SHV) related to susceptibility to ampicillin in Klebsiella pneumoniae. AB - Klebsiella pneumoniae usually shows intrinsic resistance to ampicillin and other beta-lactams. bla(SHV) is thought to be a key beta-lactamase gene responsible for this intrinsic resistance to ampicillin. Nevertheless, surveys of clinical strains reveal that some isolates of K. pneumoniae that carry bla(SHV) remain susceptible to ampicillin. To explore susceptibility to ampicillin in relation to bla(SHV) in K. pneumoniae, we analysed the existence and transcription of bla(SHV) and determined beta-lactamase activity as well as the susceptibilities to clinically relevant beta-lactams, including ampicillin in 160K. pneumoniae isolates from China. In total, 141 isolates (88.1%) were detected as bla(SHV) positive, 20 (14.2%) of which were found to be broadly susceptible to all beta lactams tested, including ampicillin. Among the 20 broadly susceptible isolates, sequencing of bla(SHV) revealed synonymous point mutations in 19 isolates and a premature stop codon in 1 isolate. Reverse transcription-polymerase chain reaction failed to detect bla(SHV) mRNA in five isolates (25%). The results demonstrate that differential expression of bla(SHV) in clinical isolates of K. pneumoniae can affect susceptibility to ampicillin. PMID- 17276040 TI - In vitro susceptibility of Spanish isolates of Neisseria gonorrhoeae to cefditoren and five other antimicrobial agents. PMID- 17276041 TI - Interaction of 5-hydroxytryptamine (serotonin) against Aspergillus spp. in vitro. AB - This study examined the direct interaction of serotonin (5-hydroxytryptamine (5 HT)) with Aspergillus species. Accumulation of 5-HT in aspergilli was investigated by immunofluorescence staining and laser confocal scanning microscopy. The influence of 5-HT on fungal ergosterol content, cell membrane integrity, fungal growth and hyphal elongation was determined. 5-HT was localised in the cytoplasm of Aspergillus spp., as 5-HT fluorescent signals appeared after 30min at 4 degrees C and in the presence of inhibitors of oxidative phosphorylation. 5-HT treatment of Aspergillus spp. significantly affected ergosterol synthesis, fungal cell membrane integrity and hyphal elongation (P<0.05). 5-HT treatment for 4h resulted in a lag of re-growth (post-antifungal effect). In conclusion, our findings suggest that 5-HT affects hyphal growth and diminishes fungal cell membrane integrity. PMID- 17276042 TI - Double-quantum filtered heteronuclear correlation spectroscopy under magic angle spinning. AB - We present a simple experimental method to extract the van Vleck second moment of a multiple-spin system under high-resolution condition. The idea is to incorporate a double-quantum (DQ) filter into the pulse sequence of heteronuclear correlation spectroscopy so that a DQ excitation profile can be obtained by measuring a series of 2D spectra. The effects of spinning frequency and proton decoupling are demonstrated on the measurements of two model compounds, viz. hydroxyapatite and brushite. Based on the results obtained for the model compounds, the P-31 homonuclear second moment of the apatite component in rat dentin is characterized. The method is generally suited for the study of bone, enamel and dentin. PMID- 17276043 TI - Calmodulin-mediated reversible immobilization of enzymes. AB - This work demonstrates the use of the protein calmodulin, CaM, as an affinity tag for the reversible immobilization of enzymes on surfaces. Our strategy takes advantage of the of the reversible, calcium-mediated binding of CaM to its ligand phenothiazine and of the ability to produce fusion proteins between CaM and a variety of enzymes to reversibly immobilize enzymes in an oriented fashion to different surfaces. Specifically, we employed two different enzymes, organophosphorus hydrolase (OPH) and beta-lactamase and two different solid supports, a silica surface and cellulose membrane modified by covalently attaching a phenothiazine ligand, to demonstrate the versatility of our immobilization method. Fusion proteins between CaM-OPH and CaM-beta-lactamase were prepared by using genetic engineering strategies to introduce the calmodulin tail at the N-terminus of each of the two enzymes. In the presence of Ca(2+), CaM adopts a conformation that favors interaction between hydrophobic pockets in CaM and phenothiazine, while in the presence of a Ca(2+)-chelating agent such as EGTA, the interaction between CaM and phenothiazine is disrupted, thus allowing for removal of the CaM-fusion protein from the surface under mild conditions. CaM also acts as a spacer molecule, orienting the enzyme away from the surface and toward the solution, which minimizes enzyme interactions with the immobilization surface. Since the method is based on the highly selective binding of CaM to its phenothiazine ligand, and this is covalently immobilized on the surface, the method does not suffer from ligand leaching nor from interference from other proteins present in the cell extract. An additional advantage lies in that the support can be regenerated by passing through EGTA, and then reused for the immobilization of the same or, if desired, a different enzyme. Using a fusion protein approach for immobilization purposes avoids the use of harsh conditions in the immobilization and/or regeneration steps, which could cause inactivation of the immobilized enzyme. Moreover, we have demonstrated that the CaM affinity tag allows immobilization of enzymes on a variety of surfaces without compromising their enzymatic activity substantially; for example, the immobilized OPH retained more than 80% of the activity of the free enzyme. Our results with beta-lactamase showed the feasibility of using a phenothiazine surface in several consecutive loading and regeneration cycles. This can be advantageous when expensive and/or difficult to obtain immobilization surfaces have to be employed; the immobilization surface could be reused to immobilize the same or a different enzyme using the CaM affinity tail. We also determined that the phenothiazine modified silica particles are stable for long periods of time, i.e., up to 2 years when stored at 4 degrees C. It is envisioned that this type of reversible immobilization may find applications in the development of reversible, reusable biosensors and bioreactors endowed with the additional advantage that the biological element at the surface of the sensor or bioreactor could be replaced under mild conditions when needed to sense or process a different target molecule. PMID- 17276044 TI - [Streptococcus pneumoniae serotypes involved in children with pleural empyemas in France]. AB - It has been suggested that the incidence of childhood empyema have increased during the last years in France without clear explanation. Streptococcus pneumoniae is responsible for the vast majority of bacteriological documented cases. Potential prevention of pleural empyemas by the heptavalent pneumococcal conjugate vaccine is dependent on adequation between specific pneumococcal serogroups present in vaccine and those responsible for empyemas. MATERIAL AND METHODS: We retrospectively collected cases of pleural empyemas registered at the National Reference Center for pneumococci (December 2002 to February 2004). Thirty children, aged 4.1+/-3.3 (SD) years, were included. RESULTS: Ten specific serogroups were identified: 1, 3, 5, 6B, 7F, 9V, 14, 18C, 19A, and 23F. Serogroups 19A and 1 were the 2 dominant serogroups and represented 50% of cases. All children infected with serotype 19A were younger than 5 years, whereas serotype 1 was identified in 80% of empyemas in children older than 5 years. Among the 30 patients enrolled, 20 (69%) were infected with serotypes not included in the conjugate vaccine. CONCLUSION: These results thus limit the potential impact of the heptavalent pneumococcal conjugate vaccine on the frequency of pleural empyemas in children. PMID- 17276045 TI - Kofoidinium, Spatulodinium and other kofoidiniaceans (Noctilucales, Dinophyceae) in the Pacific Ocean. AB - Examples of rarely reported dinoflagellates of the family Kofoidiniaceae F.J.R. Taylor (Noctilucales) from the northwest, equatorial and southeast Pacific Ocean are described and illustrated. Kofoidinium was the most ubiquitous genus with a maximum abundance of 10 cells L(-1). Specimens of this genus were identified to four species: Kofoidinium sp. that showed a pointed extension that emerges from the antero-ventral region and K. velelloides, both of which had diameters that ranged from 40 to 200 microm; Kofoidinium pavillardii which showed a rounded epitheca and a larger size (approximately 300-700 microm in diameter); and another species, tentatively identified as K. splendens, that contained red circular inclusions. Further research is needed to clarify the characteristics that separate K. splendens from the other species. This study is the first to record the genus Spatulodinium in tropical waters and in the southern hemisphere. S. cf. pseudonoctiluca was found in the southeast Pacific Ocean, as well as other smaller specimens with a different shape or disposition of the tentacle that may belong to two other species. In the northwest and equatorial Pacific, specimens of Spatulodinium showed a green pigmentation that suggested the existence of the first species known in the order Noctilucales to contain its own chloroplasts. Immature stages of kofoidiniaceans, some containing symbiotic microalgae, are illustrated, as well as mature stages related to Pomatodinium and to unknown genera of kofoidiniaceans. Kofoidiniaceans are shown to be common and widely distributed in the Pacific, and are probably also frequent in other oceans, but are rarely recognised. PMID- 17276046 TI - Morphological redescription of two endocommensal ciliates, Entorhipidium fukuii Uyemura, 1934 and Madsenia indomita (Madsen, 1931) Kahl, 1934 from digestive tracts of sea urchins of the Yellow Sea, China (Ciliophora; Scuticociliatida). AB - Definitions of the genera Entorhipidium and Madsenia have been updated on the basis of the results of studies on the living morphology and infraciliature of the endocommensal ciliates, Entorhipidium fukuii Uyemura, 1934 and Madsenia indomita (Madsen, 1931) Kahl, 1934, isolated from digestive tracts of the sea urchin, Hemicentrotus pulcherrimus. Entorhipidium are flattened marine endocommensal scuticociliates with a sigmoid body shape and conspicuous tail; the buccal cavity is in the anterior half of the cell and the buccal ciliature has a Uronema-like pattern; the somatic kineties form both apical and post-oral sutures. Because of this new definition, a new combination is suggested: Entorhipidium caudatum (Poljansky, 1951) nov. comb. (basionym: Cryptochilidium caudatum Poljansky, 1951). Madsenia are flattened, slender-bodied endocommensal scuticociliates, having a buccal cavity in the anterior half of the cell with M1 and M2 fused into a single structure and both M3 and the paroral membrane short; the somatic kineties form an anterior suture; no caudal bristle was observed. PMID- 17276047 TI - Application of nutrigenomic concepts to Type 2 diabetes mellitus. AB - The genetic makeup that individuals inherit from their ancestors is responsible for variation in responses to food and susceptibility to chronic diseases such as Type 2 diabetes mellitus (T2DM). Common variations in gene sequences, such as single nucleotide polymorphisms, produce differences in complex traits such as height or weight potential, food metabolism, food-gene interactions, and disease susceptibilities. Nutritional genomics, or nutrigenomics, is the study of how foods affect the expression of genetic information in an individual and how an individual's genetic makeup affects the metabolism and response to nutrients and other bioactive components in food. Since both diet and genes alter one's health and susceptibility to disease, identifying genes that are regulated by diet and that cause or contribute to chronic diseases could result in the development of diagnostic tools, individualized intervention, and eventually strategies for maintaining health. Translating this research through clinical studies promises contributions to the development of personalized medicine that includes nutritional as well as drug interventions. Reviewed here are the key nutrigenomic concepts that help explain aspects of the development and complexity of T2DM. PMID- 17276048 TI - Liquid herbal drug preparation from the root of Pelargonium sidoides is effective against acute bronchitis: results of a double-blind study with 124 patients. PMID- 17276049 TI - Periconceptional alcohol consumption-induced changes in embryonic prostaglandin E levels in mouse organogenesis: modulation by nitric oxide. AB - The mechanisms of the teratogenic effects of maternal alcohol consumption remain unclear. The aim of the present work was to study the organogenic PGE(2) levels and the modulation of PGE(2) levels by NO after periconceptional alcohol ingestion. Female mice were intoxicated with a 10% ethanol in drinking water before pregnancy and up to day 10 of gestation. The PGE(2) released from organogenic embryos was measured by radio immunoassay following incubation with or without the addition of either a NO donor or a NO synthase (NOS) inhibitor. In the ethanol-treated females, we found increased percentages of retarded embryos, associated with a significantly elevated resorption rate (p<0.05), very high quantities of morphologically abnormal E.10 embryos (p<0.001) and significantly increased PGE(2) release, as compared to the embryo parameters of control females. While in the control-derived E.10 embryos the NO donor produced significantly increased PGE(2) release, in the ethanol-derived embryos decreased quantities of PGE(2) were observed. L-NMMA inhibited PGE(2) release in both control and ethanol-derived embryos at different concentrations, whereas it decreased PGE(2) content in controls but not in ethanol-derived embryos. The periconceptional alcohol ingestion produced excessive PGE(2) release, decreased PGE(2) content and disruption of the regulatory NO-PGE(2) pathways. These PGs alterations may be related to delayed organogenesis and abnormal neural tube development after chronic periconceptional consumption of alcohol. PMID- 17276050 TI - Humoral immunity, inflammation and cancer. AB - Clinical and experimental data now clearly indicate that chronic inflammation significantly contributes to cancer development. Emerging out of these studies is an appreciation that persistent humoral immune responses exacerbate recruitment and activation of innate immune cells in neoplastic microenvironments where they regulate tissue remodeling, pro-angiogenic and pro-survival pathways that together potentiate cancer development. Population-based studies examining individuals with chronic inflammatory disorders have revealed that states of suppressed cellular immunity, in combination with enhanced humoral immunity and humoral immunity-associated cytokines, cooperate and effectively suppress anti tumor immune responses while simultaneously enhancing angiogenesis and presumably overall cancer risk in afflicted tissue. In addition, studies in transgenic mouse models of de novo organ-specific cancer development have revealed that inflammation mediated by immunoglobulins and immune complexes might be functionally significant parameters of tumor promotion and progression. These recent advances support the hypothesis that enhanced states of local humoral and innate immune activation, in combination with suppressed cellular immunity and failed cytotoxic T cell anti-tumor immunity, alter cancer risk and therefore represent powerful targets for anti-cancer immunotherapeutics. PMID- 17276051 TI - Comparison of bronchodilator responses of levosalbutamol and salbutamol given via a pressurized metered dose inhaler: a randomized, double blind, single-dose, crossover study. AB - BACKGROUND: Salbutamol, the most widely used short-acting beta(2)-agonist, consists of a racemic mixture of equal amounts of two enantiomers, (R)-salbutamol and (S)-salbutamol. The bronchodilator effects of salbutamol are attributed entirely to (R)-salbutamol (levosalbutamol), while (S)-salbutamol has been shown to possess bronchospastic and pro-inflammatory effects both in vitro and in vivo studies. Levosalbutamol, the (R)-enantiomer of salbutamol is currently available only in a liquid formulation for use via a nebulizer. Recently, levosalbutamol to be administered via a pressurized metered dose inhaler (pMDI) has been developed. AIMS: To compare the time-dependent bronchodilator responses of single doses of 100mcg levosalbutamol and 200 mcg racemic salbutamol administered via a pMDI in subjects with stable mild-to-moderate bronchial asthma over a period of 6h. METHODS: Single doses of 100 mcg levosalbutamol, 200 mcg salbutamol and placebo were administered with a pMDI in 30 stable asthmatic subjects in a randomized, double-blind, placebo-controlled, three-way cross over study. Forced expiratory volume in 1s (FEV(1)) and forced vital capacity (FVC) were measured at baseline, and over 6h post-study drug administration. RESULTS: Levosalbutamol and salbutamol produced significantly better bronchodilator responses than placebo. Both the drugs showed equivalent time-dependent bronchodilator responses as measured by area under curve for percent change in FEV(1) and FVC over 6h. The time to onset of action, mean maximum bronchodilator response and duration of bronchodilator response were similar between levosalbutamol and salbutamol. CONCLUSION: A single dose of 100 mcg levosalbutamol administered by a pMDI produced a similar bronchodilator response as salbutamol when measured over 6h in subjects with stable, mild-to-moderate bronchial asthma. PMID- 17276052 TI - Models for intestinal fermentation: association between food components, delivery systems, bioavailability and functional interactions in the gut. AB - There is increasing interest in the human colonic microbiota and in the way its metabolic activities impact on host health and well-being. For most practical purposes, however, the large bowel is inaccessible for routine investigation, and a variety of animal and in vitro model systems have been developed to study the microbiota. In vitro models range from simple closed systems using pure or defined mixed populations of bacteria, or faecal material, to more sophisticated complex multistage continuous cultures that are able to simulate many of the spatial, temporal and environmental attributes that characterize microbiological events in different regions of the large gut. Recent developments using these systems have enabled modelling of surface colonisation and biofilm development, a hitherto neglected area of study. PMID- 17276053 TI - TPM3-ALK expression induces changes in cytoskeleton organisation and confers higher metastatic capacities than other ALK fusion proteins. AB - Translocations of the anaplastic lymphoma kinase (ALK) gene result in the production of a number of oncogenic ALK fusion proteins implicated in tumour development. We have previously shown that X-ALK fusion proteins have differential effects on the proliferation, transformation, and invasion properties of NIH3T3 cells in vitro. In the present study, we have investigated the metastatic potential of various X-ALK expressing cell lines using an experimental lung metastasis assay. We have shown that TPM3-ALK expression bestows higher metastatic capacities than other X-ALK fusion proteins and in addition, that TPM3-ALK fusion protein expression specifically induces changes in cell morphology and cytoskeleton organisation. Co-immunoprecipitation studies demonstrate a specific interaction between TPM3-ALK and endogenous tropomyosin. Together the specific actions of TPM3-ALK on the cytoskeleton organisation offer an interesting hypothesis with respect to the higher cell motility and metastatic potential of this fusion protein. PMID- 17276054 TI - 1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization, in the HL-1 cardiac myocyte. AB - The steroid hormone 1,25(OH)(2)-vitamin D(3) [1,25D] has been shown to affect the growth and proliferation of primary cultures of ventricular myocytes isolated from neonatal rat hearts. The research presented here shows that the vitamin D receptor [VDR] is present in murine cardiac myocytes (HL-1 cells), and that 1,25D affects the growth, proliferation and morphology of these cells. In addition we show that 1,25D effects expression of ANP, myotrophin, and c-myc. Furthermore, 1,25D effects expression and localization of the VDR within the cell. Murine HL-1 cardiac myocytes were grown and treated with 1,25D in culture, and growth and morphology were assessed with microscopic analysis. Cells were counted and protein levels were evaluated through Western blot analysis. Subcellular localization of the VDR was determined using immunofluorescence and confocal microscopy. 1,25D was found to decrease proliferation and alter cellular morphology of the HL-1 cells. Treatment with 1,25D increased expression of myotrophin while decreasing expression of atrial natriuretic peptide [ANP] and c myc. 1,25D treatment also increased expression and nuclear localization of the VDR in these cardiac myocytes. Thus 1,25D is an important hormone involved in modulating and maintaining heart cell structure and function. PMID- 17276056 TI - Synthesis of novel diaryl ethers and their evaluation as antimitotic agents. AB - A series of novel diaryl ethers possessing various functional groups were synthesized and evaluated for antiproliferative activity in human myeloid leukemia HL-60 cells. Among the compounds examined, compounds 10, 17, 20, 24, and 33 showed moderate to potent antiproliferative activity. These derivatives were further examined in terms of their abilities to inhibit tubulin polymerization; however, all of the tested compounds were relatively ineffective. The reference compound E7010 with an IC(50) of 0.34 microM exhibited potent antiproliferative activity and significantly inhibited tubulin polymerization in a dose-dependent manner. PMID- 17276055 TI - Orally active 4-amino-5-diarylurea-furo[2,3-d]pyrimidine derivatives as anti angiogenic agent inhibiting VEGFR2 and Tie-2. AB - During our effort to develop dual VEGFR2 and Tie-2 inhibitors as anti-angiogenic agents for cancer therapy, we discovered 4-amino-5-(4-((2-fluoro-5 (trifluoromethyl)phenyl)- aminocarbonylamino)phenyl)furo[2,3-d]pyrimidine (8a) possessing strong inhibitory activity at both the enzyme and cellular level against VEGFR2 and Tie-2. Compound 8a demonstrated high pharmacokinetic exposure through oral administration, and showed marked tumor growth inhibition and anti angiogenic activity in mouse HT-29 xenograft model via once-daily oral administration. PMID- 17276057 TI - Synthesis and antibacterial activity of 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine quinolones. AB - Synthesis and antibacterial activity of a number of substituted 4,5,6,7 tetrahydro-thieno[3,2-c]pyridine quinolones is reported. The antibacterial activities were evaluated in standard in vitro MIC assay method. Some of the compounds showed in vitro (MIC) antibacterial activity comparable to those of Gatifloxacin, Ciprofloxacin, and Sparfloxacin. PMID- 17276058 TI - Validate antibacterial mode and find main bioactive components of traditional Chinese medicine Aquilegia oxysepala. AB - Traditional Chinese medicines have been used for thousands of years and are still being used as one of the regular treatments for many diseases. However, their mechanisms were still unknown. In this investigation, a possible procedure combining metabonomics and principal component analysis to investigate antibacterial modes of action and find main antimicrobial component in traditional Chinese medicine, Aquilegia oxysepala, is developed. Metabolic profiles of Staphylococcus aureus treated with nine antibiotics of known modes of action and with A. oxysepala were acquired by HPLC/DAD/ESI-MS. After statistical processing by principal components analysis on metabolic profiles, two conclusions could be drawn: (1) the target of A. oxysepala may be similar to that of lincolmensin, erythromycin, chloromycetin, streptomycin, and acheomycin, whose targets are protein; (2) its bioactive component playing main antimicrobial roles on S. aureus may be maguoflorine. PMID- 17276060 TI - Thiazolone-acylsulfonamides as novel HCV NS5B polymerase allosteric inhibitors: convergence of structure-based drug design and X-ray crystallographic study. AB - A novel series of thiazolone-acylsulfonamides were designed as HCV NS5B polymerase allosteric inhibitors. The structure based drug designs (SBDD) were guided by docking results that revealed the potential to explore an additional pocket in the allosteric site. In particular, the designed molecules contain moieties of previously described thiazolone and a newly designed acylsulfonamide linker that is in turn connected with a substituted aromatic ring. The selected compounds were synthesized and demonstrated low muM activity. The X-ray complex structure was determined at a 2.2A resolution and converged with the SBDD principle. PMID- 17276059 TI - Modifications of the GSK3beta substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics. AB - Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3beta substrate mimetic inhibitors towards the development of a potent, small molecule substrate mimetic inhibitor of Akt. PMID- 17276061 TI - In vitro and in vivo profile of 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl) amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), a novel potent MTP inhibitor for obesity. AB - The synthesis of a novel gut selective MTP inhibitor, 5-[(4'-trifluoromethyl biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), and its in vitro and in vivo profile are described. Dirlotapide (3) demonstrated excellent potency against MTP enzyme in HepG2 cells and canine hepatocytes. This novel MTP inhibitor also showed excellent efficacy when tested in a canine food intake model. PMID- 17276062 TI - Transformation of the amyloidogenic peptide amylin(20-29) into its corresponding peptoid and retropeptoid: access to both an amyloid inhibitor and template for self-assembled supramolecular tapes. AB - The highly amyloidogenic peptide sequence of amylin(20-29) was transformed into its corresponding peptoid and retropeptoid sequences to design a novel class of beta-sheet breaker peptides as amyloid inhibitors. This report describes the synthesis of the chiral peptoid building block of L-isoleucine, the solid phase synthesis of the peptoid and retropeptoid sequences of amylin(20-29), and the structural analysis of these amylin derivatives in solution by infrared spectroscopy, circular dichroism, and transmission electron microscopy. It was found that the peptoid sequence did not form amyloid fibrils or any other secondary structures and was able to inhibit amyloid formation of native amylin(20-29). Although the retropeptoid did not form amyloid fibrils it had only modest amyloid inhibitor properties since supramolecular tapes were formed. PMID- 17276063 TI - Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit. AB - A novel series of pyrrolidine-constrained phenethylamines were developed as dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2 diabetes. The cyclohexene ring of lead-like screening hit 5 was replaced with a pyrrolidine to enable parallel chemistry, and protein co-crystal structural data guided the optimization of N-substituents. Employing this strategy, a >400x improvement in potency over the initial hit was realized in rapid fashion. Optimized compounds are potent and selective inhibitors with excellent pharmacokinetic profiles. Compound 30 was efficacious in vivo, lowering blood glucose in ZDF rats that were allowed to feed freely on a mixed meal. PMID- 17276064 TI - Discovery of novel benzimidazolones as potent non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains. AB - Molecular modeling studies led to the rational discovery of N(1)-arylsulfonyl-1,3 dihydro-2H-benzimidazol-2-one as a novel template for the design of new non nucleoside reverse transcriptase inhibitors (NNRTIs) that are active against wild type and mutant strains of HIV-1. It is worth noting that compound 3 proved to have antiretroviral activity similar to that of efavirenz and greater than that of nevirapine, two of the three NNRTIs currently available in antiretroviral therapy. PMID- 17276066 TI - Balance during obstacle crossing following stroke. AB - Difficulty negotiating obstacles may contribute to the high falls rate following stroke. This study examined the impact of stroke on balance during obstacle crossing. Centre of mass (COM) and centre of pressure (COP) were measured as 12 stroke subjects and 12 unimpaired subjects stepped over a 4 cm high obstacle at self-selected speed. Unimpaired subjects also walked at speeds matched to their yoked stroke subject. Compared with unimpaired subjects at matched speed, at unaffected lead toe clearance, anterior-posterior (AP) separation between COM and COP increased in stroke subjects, which might indicate instability. Step lengths before and after the obstacle tended to be reduced which could increase the risk of losing balance forwards. The COM AP velocity was reduced at affected lead toe off following stroke, which may minimise instability. Following stroke the COM and COP were positioned more posteriorly during affected lead toe clearance, which might also assist stability. PMID- 17276065 TI - Introduction of a liaison nurse role in a tertiary paediatric ICU. AB - INTRODUCTION: The Royal Children's Hospital in Melbourne is the only dedicated paediatric hospital in Victoria (population 5 million). The role of the PICU liaison nurse (LN) has been developed to bridge the gap between PICU and the wards within the hospital with the aim of reducing the number of readmissions to the PICU within 48h of discharge. RESULTS: The year of the PICU LN trial (July 2004-June 2005), 1388 patients were discharged from PICU. Sixty-seven patients had unplanned readmission within 48h. This readmission rate (4.8%) is lower than the readmission rate (5.4%) during the year prior to the implementation of the PICU LN. Staff and parents were surveyed at the end of the 12-month trial to evaluate the introduction of the LN role. The response from the surveys was very positive, 98.5% of staff believed the PICU LN to be beneficial and to have made a valuable impact on PICU-ward transfers. Ninety-nine percent of surveyed parents agreed that the LN role is a good idea. CONCLUSION: The PICU LN role at RCH has shown many positive outcomes including improved communication, ward education, improved patient outcomes and decreased readmission rates to ICU. PMID- 17276067 TI - Changes in EMG characteristics and metabolic energy cost during 90-min prolonged running. AB - This study quantified the interaction of integrated electromyography (iEMG) obtained from the vastus lateralis and the metabolic energy cost of running (Cr), an index to assess running economy, during 90-min prolonged running. The iEMG during running was divided into eccentric (ECC) and concentric (CON) phases using a force platform and a knee-joint goniometer. The ratio of ECC to CON (ECC/CON ratio) significantly decreased during 90-min prolonged running in novice distance runners, which would be explained by an increase in muscle activity during the CON phase of running. The average Cr value significantly increased during 90-min prolonged running. The individual's Cr values significantly correlated with the ECC/CON ratio (r=-0.702, P<0.05). These results suggest that changes in the ECC/CON ratio and Cr value during prolonged running are associated. PMID- 17276069 TI - Targeting malignant glioma survival signalling to improve clinical outcomes. AB - Malignant gliomas are common and aggressive brain tumours in adults. Current treatments for glioblastoma multiforme result in a poor median survival of less than 12 months. The blood-brain barrier restricts the delivery of many chemotherapies to the central nervous system, contributing to the failure of treatment. PI3K/Akt and Ras/MAPK pathways have been identified as important oncogenic pathways in these tumours. The PI3K/Akt pathway mediates cell survival and growth, whereas the Ras/MAPK pathway signals cell differentiation, proliferation and anti-apoptosis. Modern targeted therapies include antibodies to circulating growth factors and cell surface receptors, as well as inhibitors of receptor tyrosine kinases and specific intracellular signalling proteins. Monotherapy with most targeted therapies produces only modest efficacy. Better results are achieved in combination with cytotoxic chemotherapies. Future therapeutics should focus on combination therapy with small lipophilic molecules. PMID- 17276068 TI - Oxylipins as developmental and host-fungal communication signals. AB - Pathogenic microbes and their hosts have acquired complex signalling mechanisms to appraise themselves of the environmental milieu in the ongoing battle for survival. Several recent studies have implicated oxylipins as a novel class of host-microbe signalling molecules. Oxylipins represent a vast and diverse family of secondary metabolites that originate from the oxidation or further conversion of polyunsaturated fatty acids. Among the microbial oxylipins, the fungal oxylipins are best characterized and function as hormone-like signals that modulate the timing and balance between asexual and sexual spore development in addition to toxin production. Coupled with other studies that implicate a role for fungal oxylipins in pathogenesis by Aspergillus and Candida spp., these results suggest that host and microbial oxylipins might interfere with the metabolism, perception or signalling processes of each other. PMID- 17276070 TI - The survivorship and results of total knee replacements converted from unicompartmental knee replacements. AB - Unicompartmental knee replacements (UKR) converted to total knee replacements (TKR) have often been viewed with scepticism because of the perceived difficulty of revising a UKR to a TKR. We present the survivorship analysis of a 77 patient cohort as well as the current results of a 35 patient cohort. There were a total of 77 patients in the survivorship study with an average follow-up of 6.9 years and an average Bristol Knee Score of 78.5. Using Kaplan-Meier survivorship analysis, a 91% survivorship at 10 years was demonstrated. The average age at revision to TKR was 66.1 years. The average follow-up period was 10.5 years and a recent clinical and radiological review of the 35 living patients showed an average Bristol Knee Score of 78.2 with 16 excellent, 11 good, five fair and three failed. CONCLUSION: The results of the UKRs have already shown it to be safe, reliable and repeatable. We believe that this study shows that revision of UKR to TKR is not technically difficult and that the results are comparable to the results of primary TKRs. PMID- 17276072 TI - Carbonic anhydrase and matrix metalloproteinase inhibitors. Inhibition of human tumor-associated isozymes IX and cytosolic isozyme I and II with sulfonylated hydroxamates. AB - A series of sulfonylated hydroxamates were synthesized and evaluated as dual inhibitors of both human carbonic anhydrases (hCAs) and matrix metalloproteinases (MMPs), two metalloenzyme families involved in carcinogenesis and tumor invasion processes. The new derivatives were tested on three CA isozymes, the cytosolic isozymes I and II, and the transmembrane, tumor-associated isozyme IX, and also on human gelatinases (MMP-2 and MMP-9). Some of the new derivatives proved to be potent and selective inhibitors of CA II, but only compounds 3b and 6b, devoid of the arylsulfonyl moiety, proved to have a better inhibitory activity on hCA IX than on hCA I and II, in the micromolar range. PMID- 17276071 TI - Synthesis and structure-antibacterial activity relationship investigation of isomeric 2,3,5-substituted perhydropyrrolo[3,4-d]isoxazole-4,6-diones. AB - The synthesis of 2,3,5-substituted perhydropyrrolo[3,4-d]isoxazole-4,6-diones (44 compounds) has been accomplished by the cycloaddition reaction of N-methyl-C arylnitrones with N-substituted maleimides. The compounds were screened for their antibacterial activities and most of them exhibited activity against Enterococcus faecalis (ATCC 29212) and Staphylococcus aureus (ATCC 25923). cis-3a and cis-3d were found fairly effective against E. faecalis (ATCC 29212) and S. aureus (ATCC 25923) with MIC values of 25 and 50microg/ml. With the changes of cis isomers of the compounds to trans, their antibacterial activities also changed against the bacteria studied. First, pharmacophoric fragments had been calculated in accordance with the rules of the electronic-topological method (ETM). Next, both active compounds and pharmacophores had been projected to the nodes of Kohonen's self-organizing maps (SOM) to obtain the weights of pharmacophore fragments as numerical descriptors, that were used after this for the associative neural networks (ASNN) training. A model for the activity prediction was developed as the result of training the ASNNs. PMID- 17276073 TI - Synthesis and alpha(1)-adrenoceptor antagonist activity of derivatives and isosters of the furan portion of (+)-cyclazosin. AB - alpha(1)-Adrenoceptor selective antagonists are crucial in investigating the role and biological functions of alpha(1)-adrenoceptor subtypes. We synthesized and studied the alpha(1)-adrenoceptor blocking properties of new molecules structurally related to the alpha(1B)-adrenoceptor selective antagonist (+) cyclazosin, in an attempt to improve its receptor selectivity. In particular, we investigated the importance of substituents introduced at position 5 of the 2 furan moiety of (+)-cyclazosin and its replacement with classical isosteric rings. The 5-methylfuryl derivative (+)-3, [(+)-metcyclazosin], improved the pharmacological properties of the progenitor, displaying a competitive antagonism and an 11 fold increased selectivity for alpha(1B) over alpha(1A), while maintaining a similar selectivity for the alpha(1B)-adrenoceptor relative to the alpha(1D)-adrenoceptor. Compound (+)-3 may represent a useful tool for alpha(1B) adrenoceptor characterization in functional studies. PMID- 17276074 TI - Novel cationic and neutral glycocholic acid and polyamine conjugates able to inhibit transporters involved in hepatic and intestinal bile acid uptake. AB - To obtain novel drugs able to inhibit transporters involved in bile acid uptake, three compounds were synthesized by conjugating N-(3-aminopropyl)-1,3 propanediamine (PA) with one (BAPA-3), two (BAPA-6), or three (BAPA-8) moieties of glycocholic acid (GC) through their carboxylic group. The expected net charge in aqueous solutions was 2+ (BAPA-3), 1+ (BAPA-6), and 0 (BAPA-8). They were purified by liquid chromatography and their purity checked by HPLC before being chemically characterized by elemental analysis, NMR, and FAB-MS. Using brush border membranes isolated from rat ileum; their ability to inhibit [(14)C]-GC transport (BAPA-3>BAPA-6>BAPA-8) was suggested. This was further investigated 48h after injecting Xenopus laevis oocytes with the mRNA of rat sodium/taurocholate (TC)-cotransporting polypeptide (Ntcp), rat apical sodium-dependent bile salt transporter (Asbt), or the human isoforms OATP-C/1B1 and OATP8/1B3 of organic anion-transporting polypeptides, when maximal functional expression was detected. BAPA-8, BAPA-6, and BAPA-3 induced no inhibition of OATP8/1B3-mediated [(3)H]-TC uptake, but dramatically reduced [(3)H]-TC uptake by OATP-C/1B1. In the cases of Ntcp- and Asbt-mediated [(3)H]-TC uptake, these were sodium-dependent and were inhibited by BAPA-6>BAPA-8>BAPA-3 and BAPA-8>BAPA-6>BAPA-3, respectively. In conclusion, our results suggest that these compounds are potentially interesting research tools for the selective modulation of liver and intestinal uptake of bile acids and other cholephilic compounds. Moreover, they may be of pharmacological usefulness to prevent the acute toxicity of compounds reaching liver cells through specific transporters or to enhance both fecal elimination of bile acids and hence cholesterol consumption for the 'de novo' synthesis of bile acids. PMID- 17276075 TI - Structure-activity relationships of methoctramine-related polyamines as muscarinic antagonist: effect of replacing the inner polymethylene chain with cyclic moieties. AB - The aim of the present paper was to investigate the role of the octamethylene spacer of methoctramine (1) on the biological profile. Thus, this spacer was incorporated into a dianiline or dipiperidine moiety to determine whether flexibility and the basicity of the inner nitrogen atoms are important determinants of potency with respect to muscarinic receptors. The most potent compound was 4, which displayed, in the functional assays, a comparable potency at muscarinic M(2) receptors with respect to 1, and, in the binding assays, a loss of potency and selectivity toward muscarinic M(1) and M(3) receptor subtypes. Both compounds were endowed with antinociceptive activity. Furthermore, in microdialysis tests in rat parietal cortex, they enhanced acetylcholine release, most likely by antagonizing presynaptic muscarinic receptor subtypes. PMID- 17276076 TI - New 1,3-dioxolane and 1,3-dioxane derivatives as effective modulators to overcome multidrug resistance. AB - Multidrug resistance (MDR) to antitumor agents represents a major obstacle to a successful chemotherapy of cancer. Overexpression of P-glycoprotein (p-gp) seems to be the major factor responsible for MDR. A large number of chemically unrelated compounds are known to interact with p-gp resulting in a decreasing resistance. In our efforts related to structure-activity studies of new potential MDR reversal agents we synthesized a series of compounds that differ in the aromatic core structure, the linker, and the basic moiety. For our search of new aromatic core structures we synthesized novel 2,2-diphenyl-1,3-dioxolane, 2,2- diphenyl-1,3-dioxane, and 4,5-diphenyl-1,3-dioxolane derivatives. A range of lipophilic linker structures and protonable basic moieties were synthesized and investigated to optimize the structure of the potential MDR-modulators. The compounds were tested in vitro using human Caco-2 cells. Both the cytotoxicity of the synthons and their ability to resensitize the cells were determined with a MTT assay. The results show that at low concentration various substances reverse tumor cell MDR. Some of the new structures show better effects than established modulators like trifluoperazine. PMID- 17276077 TI - Therapeutic immunization with a glatiramer acetate derivative does not alter survival in G93A and G37R SOD1 mouse models of familial ALS. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. The cause of motor neuron degeneration remains largely unknown, and there is no potent treatment. Overexpression of various human mutant superoxide dismutase-1 (SOD1) genes in mice and rats recapitulates some of the clinical and pathological characteristics of sporadic and familial ALS. Glatiramer acetate (GA) is an approved drug for the treatment of multiple sclerosis and neuroprotective properties in some neurodegenerative conditions. A recent report suggested that GA immunization could delay disease progression in some, but not all, G93A SOD1 transgenic mouse models of amyotrophic lateral sclerosis (ALS). Moreover, it has been theorized that derivatives of GA could enhance immunogenicity and positively affect disease outcomes. The purpose of our study was to assess the neuroprotective efficacy of TV-5010, a high molecular weight GA, in three different SOD1 mutant mouse models. We used large numbers of two SOD1 transgenic mouse strains overexpressing the G93A mutation, B6SJL-TgN[SOD1-G93A]1Gur and B6.Cg-Tg(SOD1-G93A)1Gur/J, and the SOD1 mutant mouse overexpressing G37R (line 29). Regardless of the frequency of injections and the dose, treatment with TV 5010 was ineffective at altering either disease onset or survival in both SOD1 G93A mutants used and in the SOD1 G37R transgenic mice; in multiple studies, disease was accelerated. These studies suggest that, at a range of dosing regimens and carrier used, TV-5010 immunization was ineffective in delaying disease in multiple preclinical therapeutic models for ALS. The biological response in animals, and ultimate clinical translation, will ultimately be dependent on careful and appropriate dose, route and carrier paradigms. PMID- 17276078 TI - Skull base chordoma mimicking a preauricular neoplasm in a child: clinicopathological features and biological behaviour. AB - INTRODUCTION: The extreme rarity of chordomas in childhood, the slow growing nature of these tumours and the diverse symptoms may cause many diagnostic problems. PATIENT: A 9-year-old girl presented with an unusual manifestation of a skull base chordoma. The clinical and pathological features were analysed. RESULT: In the present case, the initial symptoms of the skull base tumour were completely misleading. The otodynia, the masticatory difficulties and the mass in the preauricular region were not characteristic of skull base chordomas. The female sex, the young age, the large tumour size and the atypical histological pattern of the tumour all indicated a very poor prognosis. CONCLUSION: The rarity of this tumour in childhood and the atypical lateral and intracranial spread resulted in a serious delay of the diagnosis and in a fatal outcome. PMID- 17276082 TI - A simple sandwich ELISA (WELYSSA) for the detection of lyssavirus nucleocapsid in rabies suspected specimens using mouse monoclonal antibodies. AB - Monoclonal antibody (MAb)-based capture enzyme-linked immunosorbent assays (ELISA) were developed for the diagnosis of rabies-suspect specimens. A combination of four mouse monoclonal antibodies directed against the rabies virus nucleocapsid was selected and used for the detection. The test was optimized and standardized so that maximum concordance could be maintained with the standard procedures of rabies diagnosis recommended by the WHO expert committee. Using prototype viruses from the different genotypes of lyssavirus and from various geographic origins and phylogenetic lineages, this paper presents a reliable, rapid and transferable diagnostic method, named WELYSSA that readily permits the detection of lyssaviruses belonging to the 7 genotypes of lyssavirus circulating in Europe, Africa, Asia and Oceania. The threshold of detection of lyssavirus nucleocapsids is low (0.8 ng/ml). With a panel of 1030 specimens received for rabies diagnostic testing, this test was found to be highly specific (0.999) and sensitive (0.970) when compared to other recommended rabies diagnostic methods. PMID- 17276083 TI - Molecular cloning of a C-type lectin (LvLT) from the shrimp Litopenaeus vannamei: early gene down-regulation after WSSV infection. AB - C-type lectin is one of the pattern-recognition proteins of the non-self innate immune system in the invertebrates. In this study, a lectin-like cDNA (LvLT) of Litopenaeus vannamei was cloned and characterized. LvLT cDNA consists of 1035 nt encoding for a protein with 345 amino acid residues. The deduced LvLT consists of two putative carbohydrate-recognition domains (CRDs) as found in most C-type lectins. The first CRD consists of an amino acid motif (QPD) for the binding of galactose and the other CRDs consist of amino acid motifs (EPN) for the binding of mannose. Except for some conserved amino acid residues, the CRD of LvLT shared an overall low amino acid sequence identity with CRDs of other lectins. Unlike other shrimp lectins, LvLT is expressed only in the hepatopancreas but not in the hemocytes as revealed by RT-PCR. When juvenile shrimp were challenged with shrimp extracts containing white spot syndrome virus (WSSV), the expression levels of LvLT decreased initially in the first 2 h and then increased to a much higher level after 4 h. The results suggest that the initial reduction in LvLT transcript level may be related to the WSSV infection in shrimp. PMID- 17276081 TI - E-cadherin promotes retinal ganglion cell neurite outgrowth in a protein tyrosine phosphatase-mu-dependent manner. AB - During development of the visual system, retinal ganglion cells (RGCs) require cell-cell adhesion molecules and extracellular matrix proteins for axon growth. In this study, we demonstrate that the classical cadherin, E-cadherin, is expressed in RGCs from E6 to E12 and promotes neurite outgrowth from all regions of the chick retina at E6, E8 and E10. E-cadherin is also expressed in the optic tectum. E-cadherin adhesion blocking antibodies specifically inhibit neurite outgrowth on an E-cadherin substrate. The receptor-type protein tyrosine phosphatase, PTPmu, associates with E-cadherin. In this manuscript, we demonstrate that antisense-mediated down-regulation of PTPmu, overexpression of catalytically inactive PTPmu and perturbation of endogenous PTPmu using a specific PTPmu inhibitor peptide results in a substantial reduction in neurite outgrowth on E-cadherin. Taken together, these findings demonstrate that E cadherin is an important adhesion molecule for chick RGC neurite outgrowth and suggest that PTPmu expression and catalytic activity are required for outgrowth on an E-cadherin substrate. PMID- 17276085 TI - Stationarity distributions of mechanomyogram signals from isometric contractions of extrinsic hand muscles during functional grasping. AB - This study investigates the stationarity of steady state mechanomyogram signals for the purpose of determining appropriate features for signal classification. Mechanomyography is the superficial recording of low frequency vibrations detected over contracting muscles. Steady state mechanomyogram signals, recorded at the belly of the extensor digitorum, flexor digitorum superficialis and flexor pollicis longus muscles during functional grasps were tested for weak stationarity. Twenty percent of the contractions were found to be non-stationary, indicating that time frequency methods may be appropriate for automatic pattern recognition of functional grasp from the mechanomyogram. The distribution of the stationary test statistic was dependent on the type of muscle contractions, suggesting that the test statistic itself might be a discriminating feature for mechanomyogram pattern recognition in applications such as multifunction prosthetic control. Since the major known source of non-stationarity was decreasing variance, it is suggested that shifts in the distribution of the test statistic may indicate the time course of relative muscle contributions to functional grasp. PMID- 17276080 TI - Regulation of lupus-related autoantibody production and clinical disease by Toll like receptors. AB - Autoantigens that contain DNA, RNA, or self-IgG are preferred targets for autoantibodies in systemic lupus erythematosus (SLE). B cells promote SLE pathogenesis by producing autoantibodies, activating autoreactive T cells, and secreting cytokines. We discuss how certain autoreactive B cells are selectively activated, with emphasis on the roles of key Toll-like receptors (TLRs). Although TLR7, which recognizes ssRNA, promotes autoimmune disease, TLR9, which recognizes DNA, unexpectedly regulates disease, despite being required for the secretion of anti-chromatin autoantibodies. We describe positive feedback loops involving B cells, T cells, DCs, and soluble mediators, and how these networks are regulated by TLR signals. PMID- 17276084 TI - Differences in the coordination of agonist and antagonist muscle groups in below knee amputee and able-bodied children during dynamic exercise. AB - A lack of co-contraction may predispose to knee instability or laxity, resulting in additional shear stress on the internal structures of the knee, especially in below-knee amputee (BKA) subjects. The purposes of this study were: (1) to provide information on how BKA children regulate agonist and antagonist muscle coordination, and (2) to quantify the level of knee co-contraction in able-bodied (AB) and BKA children during the stepping-in-place (SIP) task. Fourteen children (7 BKA vs. 7 AB), paired for age, weight and height, participated in this study. One-way ANOVA with Newman-Keuls post hoc tests (p<0.05) were used to compare peak power, the co-contraction index, and the resultant agonist and antagonist moments during different phases of SIP. Statistical analysis revealed that BKA children perform the task with similar kinematics than AB children while they generated less co-contraction in both their non-amputated limb and amputated limb, notably because the two groups of children used different agonist and antagonist muscles during the same periods of the SIP. This lack of co-contraction may reduce knee stability and may stress the internal structures of the knee in both the NAL and AL, and may lead to the development of premature knee osteoarthritis. PMID- 17276086 TI - Variability in response criteria affects estimates of conscious identification and unconscious semantic priming. AB - Three experiments examined the role of response criteria in a masked semantic priming paradigm using an exclusion task. Experiment 1 used on-line prime-report ("report the prime if you saw it") and exclusion instructions in which participants were told to avoid completing a word stem (e.g. mo-) with a word related to a prime (e.g. cash) flashed for 0, 38 or 212ms. Semantic priming (i.e. exclusion failure) was significant in the items analysis, but was moderated by peoples' ability to report the prime in the participant analysis. Prime-report thresholds in Experiment 2 were made more liberal by instructing participants to guess on every trial. Prime-report increased from Experiment 1 as exclusion failures were eliminated. Experiment 3 clarified the relationship between awareness and prime identification using an on-line measure of confidence and different liberal prime report instructions. The current findings suggest that the ability to act upon (via exclusion performance) and report information in a masked prime is determined by a variable response criterion, which can be manipulated as an independent variable. PMID- 17276088 TI - Separate conflict-specific cognitive control mechanisms in the human brain. AB - To ensure optimal task performance, the human brain detects and resolves conflict in information processing via a cognitive control system. However, it is not known whether conflict resolution relies on a single central resource of cognitive control, or on a collection of independent control mechanisms that deal with different types of conflict. In order to address this question, we assessed behavioral and blood-oxygen-level-dependent (BOLD) responses during the simultaneous detection and resolution of two sources of conflict in a modified color-naming Stroop task: conflict stemming from incompatibility between the task relevant and an irrelevant stimulus feature (stimulus-based or Stroop conflict), and conflict stemming from incompatibility between an irrelevant stimulus feature and response features (response-based or Simon conflict). Results show that control mechanisms recruited by stimulus-based conflict resolve stimulus-based conflict, but do not affect the resolution of response-based conflict, and vice versa. The resolution of response-based conflict was distinguished by modulation of activity in premotor cortex, whereas resolution of stimulus-based conflict was distinguished by the modulation of activity in parietal cortex. These results suggest that the human brain flexibly adopts, and independently controls, conflict-specific resolution strategies, biasing motor programming to resolve response-based conflict, and biasing stimulus representations to resolve stimulus based conflict. We propose a non-centralized, modular architecture of cognitive control, where separate control resources operate in parallel, and are recruited in a context-sensitive manner. PMID- 17276087 TI - Hue maps in primate striate cortex. AB - The macaque striate cortex (V1) contains neurons that respond preferentially to various hues. The properties of these hue-selective neurons have been studied extensively at the single-unit level, but it is unclear how stimulus hue is represented by the distribution of activity across neuronal populations in V1. Here we use the intrinsic optical signal to image V1 responses to spatially uniform stimuli of various hues. We found that (1) each of these stimuli activates an array of patches in the supragranular layers of the parafoveal V1; (2) the patches activated by different hues overlapped partially; 3) the peak locations of these patches were determined by stimulus hue. The peaks associated with various hues form well-separated clusters, in which nearby peaks represent perceptually similar hues. Each cluster represents a full gamut of hue in a small cortical area ( approximately 160 microm long). The hue order is preserved within each peak cluster, but the clusters have various geometrical shapes. These clusters were co-localized with regions that responded preferentially to chromatic gratings compared with achromatic ones. Our results suggest that V1 contains an array of hue maps, in which the hue of a stimulus is represented by the location of the peak response to the stimulus. The orderly, organized hue maps in V1, together with the recently discovered hue maps in the extrastriate cortical area V2, are likely to play an important role in hue perception in primates. PMID- 17276089 TI - Defining the limits of taxonomic conservatism in host-plant use for phytophagous insects: molecular systematics and evolution of host-plant associations in the seed-beetle genus Bruchus Linnaeus (Coleoptera: Chrysomelidae: Bruchinae). AB - In this study, we have investigated the limits of taxonomic conservatism in host plant use in the seed-beetle genus Bruchus. To reconstruct the insect phylogeny, parsimony and multiple partitioned Bayesian inference analyses were conducted on a combined data set of four genes. Permutation tests and both global and local maximum-likelihood optimizations of host preferences at distinct taxonomic levels revealed that host-fidelity is still discernible beyond the host-plant tribe level, suggesting the existence of more important than previously thought evolutionary constraints, which are further discussed in details. Our tree topologies are also mostly consistent with extant taxonomic groups. Through the analysis of this empirical data set we also provide meaningful insights on two methodological issues. First, Bayesian inference analyses suggest that partitioning by using codon positions greatly increase the accuracy of phylogenetical reconstructions. Regarding reconstruction of ancestral character states through maximum likelihood, the present study also highlights the usefulness of local optimizations. The issue of over-parameterization is also addressed, as the optimizations with the most parameter-rich models have returned the most counterintuitive results. PMID- 17276090 TI - Ribosomal RNA genes and deuterostome phylogeny revisited: more cyclostomes, elasmobranchs, reptiles, and a brittle star. AB - This is an expanded study of the relationships among the deuterostome animals based on combined, nearly complete 28S and 18S rRNA genes (>3925 nt.). It adds sequences from 20 more taxa to the approximately 45 sequences used in past studies. Seven of the new taxa were sequenced here (brittle star Ophiomyxa, lizard Anolis, turtle Chrysemys, sixgill shark Hexanchus, electric ray Narcine, Southern Hemisphere lamprey Geotria, and Atlantic hagfish Myxine for 28S), and the other 13 were from GenBank and the literature (from a chicken, dog, rat, human, three lungfishes, and several ray-finned fishes, or Actinopterygii). As before, our alignments were based on secondary structure but did not account for base pairing in the stems of rRNA. The new findings, derived from likelihood based tree-reconstruction methods and by testing hypotheses with parametric bootstrapping, include: (1) brittle star joins with sea star in the echinoderm clade, Asterozoa; (2) with two hagfishes and two lampreys now available, the cyclostome (jawless) fishes remain monophyletic; (3) Hexanchiform sharks are monophyletic, as Hexanchus groups with the frilled shark, Chlamydoselachus; (4) turtle is the sister taxon of all other amniotes; (5) bird is closer to the lizard than to the mammals; (6) the bichir Polypterus is in a monophyletic Actinopterygii; (7) Zebrafish Danio is the sister taxon of the other two teleosts we examined (trout and perch); (8) the South American and African lungfishes group together to the exclusion of the Australian lungfish. Other findings either upheld those of the previous rRNA-based studies (e.g., echinoderms and hemichordates group as Ambulacraria; orbitostylic sharks; batoids are not derived from any living lineage of sharks) or were obvious (monophyly of mammals, gnathostomes, vertebrates, echinoderms, etc.). Despite all these findings, the rRNA data still fail to resolve the relations among the major groups of deuterostomes (tunicates, Ambulacraria, cephalochordates and vertebrates) and of gnathostomes (chondrichthyans, lungfishes, coelacanth, actinopterygians, amphibians, and amniotes), partly because tunicates and lungfishes are rogue taxa that disrupt the tree. Nonetheless, parametric bootstrapping showed our RNA-gene data are only consistent with these dominant hypotheses: (1) deuterostomes consist of Ambulacraria plus Chordata, with Chordata consisting of tunicates and 'vertebrates plus cephalochordates'; and (2) lungfishes are the closest living relatives of tetrapods. PMID- 17276091 TI - Eyelid myoclonia with absences: routine EEG is sufficient to make a diagnosis. AB - PURPOSE: To identify the prevalence, clinical characteristics and routine EEG features of the syndrome of eyelid myoclonia with absences (EMA) using a retrospective case control study design. METHODS: EEGs from 1996 to 2005 were searched using the following keywords: eyelid flutter, eyelid blinking, tics, idiopathic generalized epilepsy, clinical absence, atypical absence and photoparoxysmal response. During the same period, patients with a diagnosis of idiopathic generalized epilepsy were identified. Patients with mainly eyelid fluttering/eyelid blinking as their seizure semiology were divided into EMA and non-EMA groups using previously published criteria and compared using parametric (Student's t-test) and non-parametric tests (Chi square) where appropriate. A p value of <0.05 was considered significant. RESULTS: The keywords identified 997 patients, 288 patients were diagnosed with idiopathic generalized epilepsy; 126 had eyelid fluttering/blinking as their major seizure semiology. After excluding 51 patients due to incomplete data, of 75 remaining patients, 26 (9.03%) had EMA. Patients with EMA were (1) older at time of first EEG (OR=2.86; 95% CI=7.00 10.23; p=0.005) (2) more likely to have an event on routine EEG (OR=3.62; 95% CI=1.28-10.19; p=0.01) (3) had >3 events per day (OR=9.73; 95% CI=2.06-45.96; p=0.0012) (4) had higher prevalence of developmental delay (OR=4.46; 95% CI=1.36 14.67; p=0.01) and (5) had normal EEG background compared to the non-EMA group. CONCLUSION: EMA is not uncommon; diagnosis can be made with good clinical history and routine EEG. As developmental delay is a common association with EMA in this study, early identification and treatment are important. PMID- 17276092 TI - Prediction of postoperative outcome with special respect to removal of hemosiderin fringe: a study in patients with cavernous haemangiomas associated with symptomatic epilepsy. AB - PURPOSE: In this study 30 patients with symptomatic epilepsy caused by cavernomas were investigated in a postoperative follow up study to assess predictors for postoperative outcome with respect to indications, time and approach of surgery. METHODS: Thirty patients with cavernomas refractory to medical treatment were scheduled for surgery based on the findings of high-resolution MR imaging and intensive EEG-video monitoring. Postoperative outcome of epilepsy was assessed by follow-up examinations based on the basis of classification by Engel and the International League against epilepsy (ILAE). RESULTS: The following variables were associated with good postoperative outcome: (1) complete resection of hemosiderin fringe surrounding the cavernoma was correlated to less postoperative seizure frequency versus incomplete resection of the hemosiderin fringe according to the outcome protocol of ILAE. (2) Lower duration of epilepsy at the time of operation was correlated to a better postoperative outcome with a benefit for recovery. (3) Absence of hemorrhage before surgery and unifocal seizure onset was a predictor for a favorable outcome, whereas bilateral or multifocal seizure onset zones showed poorer postoperative outcomes. (4) In patients with dual pathology (hippocampal sclerosis in addition to a cavernoma), lesionectomy plus hippocampectomy as opposed to lesionectomy only, had a better outcome than single lesionectomy. CONCLUSION: Postoperative outcome in patients with cavernomas should be the topic of further prospective multicenter studies involving a large number of patients. In addition to the ideal operation time and handling of dual pathology the role of extended resection including perilesional hemorrhages should be taken into account. PMID- 17276094 TI - Knee osteoarthritis in community-dwelling older adults: are there characteristic patterns of pain location? AB - OBJECTIVE: To determine whether there are characteristic patterns of pain location associated with knee osteoarthritis (OA) among community-dwelling older adults. DESIGN: Population-based, cross-sectional survey of 697 adults aged 50 years and over reporting knee pain within the past 6 months. Pain at 13 individual sites at or around the knee was coded. Pain locations in participants with and without "symptomatic knee OA" (defined as symptoms on most days in the past month, at least a definite osteophyte on plain X-ray, and current pain intensity of at least 2 out of 10) were compared. Participants were then grouped by pattern of knee pain location, and their clinical and radiographic characteristics compared. RESULTS: Generalised knee pain (n=313) and medial knee pain (either in isolation or with peripatellar or lateral knee pain: n=175) were the most common patterns. Medial knee pain and distally radiating pain were significantly more likely in those with symptomatic knee OA. Individuals with generalised knee pain with radiation had more persistent, severe pain, and a relatively high proportion had moderate or severe radiographic disease. CONCLUSION: No single pattern of pain location is pathognomonic for knee OA. Attention towards the role of peripheral nociception and central sensitisation in producing medial knee pain and distally radiating knee pain is warranted. PMID- 17276093 TI - Calcification of human articular knee cartilage is primarily an effect of aging rather than osteoarthritis. AB - OBJECTIVE: Pathologic calcification of articular cartilage in human knees is often associated with advanced age and conditions of osteoarthritis (OA). Coincidently, most studies that have characterized calcification in joint cartilage have examined populations that are aged and presenting with clinical symptoms. Generally, these studies rely upon relatively insensitive plain radiographs or synovial fluid crystal analyses to quantify calcium levels. The purpose of this study was to examine the relationship between cartilage calcification and aging in an unselected donor population of diverse age using highly sensitive calcification imaging. METHODS: A group of 106 knee blocks were obtained from 56 individual donors (25 females and 31 males, aged 12-74, avg. 50.3 years). Condylar surfaces were graded on a 4-point OA grading scale for cartilage degeneration. The condyles were cut into approximately 7-10mm thick slabs. Using a Faxitron radiography system, high-resolution images were taken of the slabs to specifically image calcification in cartilage. The quantified calcification areas were then analyzed and correlations with both OA grade and age were assessed. RESULTS: Every knee presented some measurable calcification. The relative calcium deposition had a significant positive correlation with age. This same positive correlation was seen between condyles showing grade 1 and 2 changes. OA grades higher than 2 did not present any further significant increase in calcium levels. CONCLUSION: These observations indicate that age rather than OA is the predominant factor driving progressive pathologic calcification in articular cartilage. PMID- 17276095 TI - Recurrent varicose veins following surgical treatment: our experience with five years follow-up. AB - OBJECTIVE: To report the 5 year outcome of varicose veins surgery and to establish the factors determining recurrence. STUDY DESIGN: Prospective observational study. MATERIALS AND METHODS: This study reports the outcome in 1326 patients treated in a day surgery centre of an institutional referral centre. Patients were investigated clinically and by colour flow duplex scanning before operation. Treatments used included flush ligation of the sapheno-femoral junction (SFJ) and the sapheno-popliteal junction (SPJ). Incompetence of the great saphenous vein (GSV) and small saphenous vein (SSV) were managed by stripping of these veins. Perforating vein ligation and hook phlebectomy were also used. Patients were evaluated 3 weeks and 5 years following treatment by clinical examination and duplex ultrasonography. RESULTS: 412 patients were excluded from the study because they failed to attend for follow-up or did not wear elastic stockings post-operatively. No residual saphenous truncal reflux was found at the initial assessment 3 weeks following surgery. After 5 years, recurrence of varicose veins occurred in 332 patients out of 1326 (25 %). Recurrences arose at the sapheno-femoral junction in 109 out of 862 patients (13%), at the sapheno-popliteal junction in 39 out of 132 patients (30%), in both saphenous regions 38 out of 107 patients (36%) and in 146 out of 225 subjects (65 %) with secondary varicose veins. CONCLUSION: Varicose veins recurred despite technically correct surgery confirmed on post-operative duplex ultrasonography. The likelihood of recurrence increased in the presence of SSV reflux, perforating vein incompetence and post-thrombotic deep vein incompetence. PMID- 17276096 TI - The Amsterdam Acute Aneurysm Trial: suitability and application rate for endovascular repair of ruptured abdominal aortic aneurysms. AB - PURPOSE: To evaluate anatomical suitability and application rate for endovascular repair of patients with a ruptured abdominal aortic aneurysm (RAAA). METHODS: The Amsterdam Acute Aneurysm trial is a multicenter randomised trial comparing open with endovascular treatment in patients with a RAAA (International Standard Randomized Controlled Trial Number (ISRCTN) 66212637). Between April 2004 and January 2006, all consecutive patients with clinical suspicion of a RAAA at presentation were assessed prospectively. Anatomical suitability for endovascular repair was based on use of an aorto-uni-iliac endovascular graft and assessed in patients with a proven aortic rupture on CT angiography (CTA). RESULTS: In 128/256 patients, presenting with clinical suspicion of a ruptured aneurysm, RAAA was diagnosed. 105 patients were brought to a trial center and CTA confirmed RAAA in 83 patients. In 38 of 83 patients (45.8%) with positive CTA, the anatomy of the aorta and iliac arteries was considered suitable for endovascular repair. Exclusion from endovascular repair was due to unsuitable infrarenal neck or iliac anatomy (37 and 8 patients respectively). Overall, endovascular treatment was applicable in 38/128 patients (29.7%) with a RAAA in the Amsterdam region and in 38 out of 105 patients (35.5%) admitted to the trial centers. CONCLUSION: In this prospective cohort of all patients with a RAAA in the Amsterdam Acute Aneurysm Trial region, the suitability for endovascular repair in patients with a RAAA confirmed on CTA is 45.8%, but the application rate was lower. PMID- 17276098 TI - Acute renal injury and dysfunction following elective abdominal aortic surgery. AB - OBJECTIVES: To evaluate the incidence of kidney injury and acute renal dysfunction (ARD) and associated risk factors in open abdominal aortic surgery. MATERIALS AND METHODS: 69 patients undergoing elective infrarenal aortic repair were included in a prospective study. Anaesthesia and haemodynamic management were standardised targeting a mean arterial pressure (MAP) of 70-90 mmHg, pulmonary artery occlusion pressure of 12-14 mmHg and cardiac index >or=2.4 l/min/m(2). Urinary albumin-creatinine and N-acetyl-B-D-glucosaminidase creatinine ratios were measured as indicators of kidney injury. The definition of ARD was based on the RIFLE criteria. RESULTS: Kidney injury was found in most patients. ARD developed in 22% of the patients, and acute renal failure in 4%. The patients with ARD were older, and had lower plasma creatinine and estimated GFR before surgery. ARD was associated with intraoperative hypotension (MAP <60 mmHg >15 min), low cardiac index (<2.4 l/min/m(2)), rhabdomyolysis, and early reoperation. Intraoperative hypotension and postoperative low cardiac output were independent risk factors for ARD in multivariate analysis. CONCLUSIONS: Kidney injury occurs in most patients undergoing infrarenal aortic surgery, but only 22% develop acute renal dysfunction. Hypotension and low cardiac output are risk factors that could be avoided by optimizing perioperative management. PMID- 17276097 TI - Preoperative nutritional status predicts the severity of the systemic inflammatory response syndrome (SIRS) following major vascular surgery. AB - OBJECTIVES: This study examined the relationship between pre-operative nutritional status and systemic inflammatory response syndrome (SIRS) or sepsis following major vascular surgery. DESIGN AND METHODS: Subjects undergoing open AAA repair, EVAR or lower limb revascularisation were studied prospectively. Pre operative nutrition was assessed clinically using Mini-Nutritional Assessment (MNA) and body composition was measured by dual energy X-ray absorptiometry (DEXA) scanning. SIRS severity was assessed for 5 post-operative days and sepsis noted within 30 days of surgery. RESULTS: Using MNA, neither SIRS severity nor sepsis occurrence differed significantly between 'well-nourished' subjects and those 'at risk of malnutrition'. Using DEXA, negative associations existed between body mass index and both SIRS score and SIRS duration. Fat free mass (FFM) was negatively associated with SIRS score and duration. Negative associations also existed between skeletal muscle mass (SMM) and SIRS score and duration. SMM was also negatively correlated with post-operative length of stay in hospital. There were no significant correlations between sepsis and any nutritional indices. CONCLUSIONS: Lower pre-operative nutritional indices, indicating protein energy malnutrition, were associated with more severe systemic inflammatory responses following major vascular surgery. PMID- 17276099 TI - A chip off the old block! AB - A 35 year old male presented 9 months after sustaining a penetrating injury to the neck with a false aneurysm of the common carotid artery (CCA). At exploration, a 5mm piece of granite was embedded in the posterior wall of the CCA with overlying endothelialisation. He was treated with segmental resection and an interposition vein graft. Apart from the risk of foreign body embolisation at the time of the original presentation, it seems remarkable that the patient did not suffer a stroke due to embolism of thrombus that one would normally have expected to form on the highly thrombogenic stone surface. PMID- 17276100 TI - Randomised clinical trial of the duration of compression therapy after varicose vein surgery. AB - OBJECTIVE: To determine whether a period of one or three weeks of compression following varicose vein surgery influenced the outcome. DESIGN: Randomised controlled trial. METHOD: 300 patients aged between 18-80 years underwent unilateral varicose vein surgery in a Day Procedure Unit. Compression bandaging was applied post-operatively for three days. Patients then wore graduated elastic compression stockings randomised to a period of either one or three weeks. Patients were assessed by questionnaire on pain scores at rest and during mobilisation for up to six weeks, total analgesic consumption, duration of time off work, any complications, and patient perception of cosmetic results at various periods up to 12 weeks following surgery. RESULTS: The mean pain score reported by patients over 6 weeks was similar in the two groups (1 week group: mean 2.18, three week group: mean 1.87). The 95% confidence interval (CI) for the mean difference in pain was (-0.05-0.66). Analysis of the pain curves at 1 week, 4 weeks and 6 weeks, showed equivalence at 4 and 6 weeks, but not for 1 week, with the group wearing stockings for only one week complaining of more pain for this period. A significant increase in the total number of analgesia tablets consumed was also found in the group wearing stockings for only one week. No significant differences were found in the other secondary endpoints - return to work (categorised as <2 weeks, 2-6 weeks or 6-12 weeks), patient satisfaction or post-operative complications. CONCLUSION: We found no benefit in wearing compression stockings for more than one week following uncomplicated high saphenous ligation with stripping of the great saphenous vein with respect to post-operative pain, number of complications, time to return to work, or patient satisfaction for up to 12 weeks following surgery. PMID- 17276101 TI - Surgical management of vascular graft infection in severely ill patients by partial resection of the infected prosthesis. AB - INTRODUCTION: In the presented retrospective study, we report on our results with partial resection of infected prosthetic grafts after aorto-bifemoral graft placement in eight male and three female patients. METHODS: In all 11 patients clinical signs of infection were observed and bacteriological cultures were positive. Three patients underwent immediate surgery for perforation of an aneurysm at the distal anastomosis, eight patients underwent elective surgery. In all cases silver-coated Dacron prostheses were implanted. Assessment of outcome was based on survival, limb salvage, persistent or recurrent infection, and prosthetic graft patency. RESULTS: In two cases, a partial wound dehiscence occurred which was treated with ambulant Vacuseal dressings for 16 and 21 days until secondary wound healing was achieved. In eight patients systemic markers of inflammation completed normalised within nine days. Follow-up CT-scans failed to demonstrate any signs of recurrent infection or peri-graft fluid collections. Patients were treated with specific antibiotic therapy for no more than three months. Post-operative bacteriological cultures were negative in all patients. The mean follow-up was 2.5+/-0.5 yrs. During follow-up, none of the patients died and there were no amputations. CONCLUSION: Despite only partial resection of the infected prostheses, the reported surgical procedure offers good results. This approach maybe particularly suitable for the treatment of elderly patients with prosthesis infections. PMID- 17276102 TI - Inferior pancreaticoduodenal artery aneurysms in association with celiac axis stenosis or occlusion. AB - PURPOSE: To describe the pathophysiology, identification and management of inferior pancreaticoduodenal artery aneurysms in association with celiac axis stenosis or occlusion has been reported. REVIEW FINDINGS: These aneurysms are thought to arise due to increased flow through the pancreaticoduodenal arcades. The arcades first enlarge, and then form focal aneurysms which may rupture. The aneurysms can be treated through endovascular techniques or by surgery, though the former is a preferred approach. PMID- 17276103 TI - Neonatal mycotic internal iliac aneurysm due to methicillin-resistant Staphylococcus aureus (MRSA) septicaemia successfully treated by coil embolisation. AB - A 12-day-old term male neonate presented with septic arthritis, multiple skin and intrabdominal abscesses and a mycotic aneurysm of the right internal iliac artery. He was diagnosed as having methicillin resistant staphylococcus aureus (MRSA) septicaemia and deemed unsuitable for surgical treatment of the aneurysm. Coil embolisation of the internal iliac artery was performed, followed by a successful recovery and with no evidence of residual or recurrent infection. The authors describe a method of treating internal iliac mycotic aneurysms in high risk patients by endovascular means, which we believe has not been attempted in this precise scenario before. PMID- 17276104 TI - Strut failure in the body of the Zenith abdominal endoprosthesis. PMID- 17276105 TI - Mobility in patients with venous leg ulceration. AB - OBJECTIVES: To compare mobility in patients with venous leg ulcers to matched controls and determine the influence of mobility, age and ulcer size on ulcer healing. METHODS: 25 leg ulcer patients, and 25 matched controls wore a mobility monitor (ActivPAL, PAL Technologies Ltd, Glasgow, Scotland)) which recorded the number of steps and amount of time spent walking, standing, sitting or lying for a one-week period. A walking index was calculated. The ulcer group were treated with compression bandaging and ulcer healing recorded over 12 weeks. RESULTS: There were 13 female subjects in each group. The median age was 70.5 (range 30 89) years. There was no difference in the amount of time either group spent standing, walking and resting. There was a significant reduction in the number of steps taken and in the walking index in the ulcer group compared to controls (ulcer group, median 6,685 steps/day, range 2074-17,999; control group median 8750, range 4917-16,043, p<0.05, Mann Whitney u test). Smaller ulcers and ulcers of recent onset were most likely to heal within 12 weeks (p=0.005 and p=0.011 respectively, Chi squared test). The percentage of time spent mobilising and resting did not influence ulcer healing (r(s)=-0.125; p=0.55). CONCLUSIONS: Mobility patterns among patients with leg ulcers are not significantly different to age matched controls. Ulcer patients take fewer steps per week compared to controls indicating they have reduced calf muscle pump function. Further studies are required to determine whether therapies which increase calf muscle activity have a role in ulcer treatment. PMID- 17276106 TI - Sleep apnea in the elderly: a specific entity? AB - Sleep apnea is highly prevalent in subjects after age 60, and affects older men and women similarly. Central apneas are often observed in addition to obstructive and mixed events. Pathogenesis of obstructive and central events during sleep in the elderly can be attributed to an amplification of well-established causes of sleep-disordered breathing (SDB) in younger adults. As in middle-aged adults, sleep-related complaints, cardiovascular diseases, depression and traffic accidents should prompt an evaluation by a sleep specialist. However, secondary enuresis and nocturia, cognitive impairment, ophthalmic conditions and repeated falls may be the main complaint in elderly subjects. Sleep studies in the elderly should systematically include reliable means to detect central apneas and periodic leg movements. Untreated SDB in the elderly appears to have a lesser impact on mortality than in middle-aged adults. However, the typical morbidity associated with the disorder in younger adults is observed in the elderly. Elderly symptomatic SDB patients tolerate CPAP no differently than younger patients and should be effectively treated. In conclusion, whether sleep apnea in the elderly represents a specific entity or the same disease as in younger subjects, with some distinctive features, is still unclear. Further research, in particular focusing on the impact of age on SDB outcomes, is needed. PMID- 17276108 TI - Efficacy of a quadrivalent vaccine against respiratory diseases caused by BHV-1, PI3V, BVDV and BRSV in experimentally infected calves. AB - The efficacy of a quadrivalent vaccine against viral bovine respiratory diseases (BRD) was assessed in four experimental studies. Calves between 2 and 9 months of age were allocated to one of two treatment groups (n=9-15) and then received either the vaccine or sterile saline in two doses approximately 3 weeks apart. Three to 5 weeks after the second injection, animals were challenged experimentally with one of the viruses, bovine herpes-virus-1 (BHV-1), parainfluenza type-3 virus (PI(3)V), bovine viral-diarrhoea virus type 1 (BVDV), or bovine respiratory syncytial virus (BRSV) and were then monitored for at least 2 weeks. The administration of the vaccine was associated with enhanced antibody response to all four viruses post-challenge, with the reduction of the amount or duration (or both) of virus shedding in the BHV-1, PI(3)V, BVDV and BRSV studies and with an improvement of some clinical signs in the BHV-1 (nasal discharge, and rectal temperature) and the PI(3)V studies (abnormal respiration, and depression). PMID- 17276109 TI - Brainstem auditory evoked responses in very low birthweight infants with chronic lung disease. AB - Very low birthweight (VLBW) infants who had prolonged oxygen dependence due to chronic respiratory problems, typically neonatal chronic lung disease (CLD), are at high risk of neurodevelopmental impairment. To assess the effect of CLD on neonatal auditory function we studied brainstem auditory evoked response (BAER) in VLBW infants who suffered CLD but no other major perinatal complications or problems. At 37-42 week postconceptional age, the latencies of waves I, III and V in CLD infants were all significantly longer than in normal term infants (all p<0.001). The differences between CLD infants and the term controls were greater for the later waves than for the earlier waves. Abnormally prolonged wave latency (>2.5 SD of the mean measurement) was seen in 7 (21.2%) CLD infants for wave I, suggesting peripheral auditory impairment, 8 (24.2%) for wave III and 14 (42.4%) for wave V. I-V interval in CLD infants was significantly longer than in the term controls (p<0.001). Seven (21.2%) infants had abnormally prolonged I-V interval, suggesting brainstem or central auditory impairment. Of these infants, 2 had both prolonged wave latencies and prolonged I-V interval, suggesting both peripheral and central auditory impairment. Similar abnormalities were found in CLD infants when compared with the BAER in birthweight- and age-matched healthy VLBW infants without CLD. CONCLUSION: Neonatal auditory function is impaired, both peripherally and centrally, at term age in VLBW infants who suffer neonatal CLD. PMID- 17276107 TI - Cyclic guanosine monophosphate phosphodiesterase-5 inhibitor promotes an endothelium NO-dependent-like vasodilation in patients with refractory hypertension. AB - The nitric oxide/cyclic-guanosine 3',5'-monophosphate signaling cascade plays an essential role in cardiovascular homeostasis but its involvement in the pathophysiology of refractory hypertension is unclear. The acute vasodilatory effect of a single oral dose of a phosphodiesterase-5 inhibitor (sildenafil citrate) on the brachial artery dilatation was evaluated in 25 normal healthy volunteers (NL) and in 25 refractory hypertensive patients (RH). Endothelial and vascular smooth muscle functions were assessed two times. First, the brachial artery response to endothelium-dependent (flow-mediated dilatation [FMD]) and independent (glyceryl trinitrate [GTN]) stimuli was examined. The FMD in NL was 14.2+/-3.2% compared to 10.3+/-3.5% in RH (P<0.001) and the GTN-induced responses were 23.5+/-6.3 in NL compared to 18.4+/-5.7% in RH (P<0.001). Two weeks later, the brachial artery responses to FMD were determined before and after the administration of sildenafil citrate. Sildenafil caused a significant, slow and progressive dilatation of the brachial artery until 45 min after administration (4.7+/-3.0%, 6.7+/-3.0% and 9.4+/-3.9% after 15', 30' and 45', respectively, in RH and 3.7+/-1.9%, 7.4+/-2.7% and 10.1+/-3.0%, respectively, in NL). A second FMD stimulus, applied 45 min after ingesting 50mg of sildenafil resulted in an additional significant increase in the vasodilatory response (from 9.4+/-3.9% to 13.0+/-4.0% in RH; P<0.001 and from 10.1+/-3.0 to 14.6+/-4.1 in NL; P<0.001), but this was still significantly less than the response to GTN. Sildenafil citrate caused brachial artery vasodilatation similar to that caused by NO released during FMD in patients with refractory hypertension. PMID- 17276110 TI - Diagnostic work-up of neuropathic pain: computing, using questionnaires or examining the patient? PMID- 17276111 TI - A parametric approach to spectral-spatial EPR imaging. AB - Continuous wave electron paramagnetic resonance imaging for in vivo mapping of spin distribution and spectral shape requires rapid data acquisition. A spectral spatial imaging technique is presented that provides an order of magnitude reduction in acquisition time, compared to iterative tomographic reprojection. The proposed approach assumes that spectral shapes in the sample are well approximated by members from a parametric family of functions. A model is developed for the spectra measured with magnetic field modulation. Parameters defining the spin distribution and spectral shapes are then determined directly from the measurements using maximum a posteriori probability estimation. The approach does not suffer approximation error from limited sweep width of the main magnetic field and explicitly incorporates the variability in signal-to-noise ratio versus strength of magnetic field gradient. The processing technique is experimentally demonstrated on a one-dimensional phantom containing a nitroxide spin label with constant g-factor. Using an L-band EPR spectrometer, spectral shapes and spin distribution are accurately recovered from two projections and a spectral window which is comparable to the maximum linewidth of the sample. PMID- 17276113 TI - Hemoglobin-oxygen-affinity and acid-base properties of blood from the fossorial mole-rat, Cryptomys hottentotus pretoriae. AB - Oxygen affinity and other hematological parameters in strictly subterranean mole rats, Cryptomys hottentotus (subspecies pretoriae) were measured immediately upon capture and after 14-21 days in captivity. The pH, hematocrit, hemoglobin (Hb) concentration, blood oxygen content, 2,3 bisphosphoglycerate (2,3 BPG) concentration and oxygen dissociation curves (ODC), as well as tonometric measurements, were determined using whole blood. Additionally ODCs were also determined for stripped hemolysates of individual animals. Compared to other mammals, blood of freshly caught animals had low pH (7.32+/-0.22), elevated hematocrits (48.4+/-3.8 %) and significantly lower P50 values for whole blood (21.1+/-1.6 mm Hg at pH 7.4) than those reported for other similar-sized fossorial and terrestrial mammals. Blood carbon dioxide content (22.4+/-3.9 mMol L(-1)), hemoglobin concentration (1.9+/-0.15 mMol L(-1)), oxygen content (164.8+/ 26 mL L(-1)), bicarbonate concentrations (22.5+/-3.5 mMol L(-1)) were within the range of values reported for similar-sized mammals. We conclude that high blood oxygen affinity, low body temperature and possibly also high hematocrit enable C. h. pretoriae to maintain an adequate oxygen supply to the tissues in a potentially hypoxic burrow atmospheres, but that the blood of this species shows no exceptional CO2 sensitivity or buffering capacity. PMID- 17276112 TI - Conformational analysis of alkali metal complexes of aspartate dianion and their interactions in gas phase. AB - The gas-phase geometry optimizations of mono and dinuclear complexes of dianionic species of aspartic acid, asp(2-) with lithium, sodium and potassium cations were carried out using density functional calculation at the B3LYP/6-311++G(d,p) level. The metal ion affinities (MIAs) of asp(2-) species and its complexes [asp M](-), M=Li(+), Na(+) and K(+) were determined using the vibrational frequency calculations at the same level of theory. The most stable complex conformer for aspartate complexes with Li(+), Na(+) and K(+) alkali cations were found as a tri coordinated form. All complexations of [asp-M](-) and [asp-M(2)] complexes were found to be exothermic reactions. Relative bond distances between the alkali metal cation M(+) and the binding atoms of aspartate ion in [asp-M](-) and [asp M(2)] complexes are in decreasing order: K(+)>Na(+)>Li(+). PMID- 17276114 TI - K+ and NH4(+) modulate gill (Na+, K+)-ATPase activity in the blue crab, Callinectes ornatus: fine tuning of ammonia excretion. AB - To better comprehend the mechanisms of ionic regulation, we investigate the modulation by Na+, K+, NH4(+) and ATP of the (Na+, K+)-ATPase in a microsomal fraction from Callinectes ornatus gills. ATP hydrolysis obeyed Michaelis-Menten kinetics with KM=0.61+/-0.03 mmol L(-1) and maximal rate of V=116.3+/-5.4 U mg( 1). Stimulation by Na+ (V=110.6+/-6.1 U mg(-1); K0.5=6.3+/-0.2 mmol L(-1)), Mg2+ (V=111.0+/-4.7 U mg(-1); K0.5=0.53+/-0.03 mmol L(-1)), NH4(+) (V=173.3+/-6.9 U mg(-1); K0.5=5.4+/-0.2 mmol L(-1)) and K+ (V=116.0+/-4.9 U mg(-1); K0.5=1.5+/-0.1 mmol L(-1)) followed a single saturation curve, although revealing site-site interactions. In the absence of NH4(+), ouabain (K(I)=74.5+/-1.2 micromol L(-1)) and orthovanadate inhibited ATPase activity by up to 87%; the inhibition patterns suggest the presence of F0F1 and K+-ATPases but not Na+-, V- or Ca2+-ATPase as contaminants. (Na+, K+)-ATPase activity was synergistically modulated by K+ and NH4(+). At 10 mmol L(-1) K+, increasing NH4(+) concentrations stimulated maximum activity to V=185.9+/-7.4 U mg(-1). However, at saturating NH4(+) (50 mmol L( 1)), increasing K+ concentrations did not stimulate activity further. Our findings provide evidence that the C. ornatus gill (Na+, K+)-ATPase may be particularly well suited for extremely efficient active NH4(+) excretion. At elevated NH4(+) concentrations, the enzyme is fully active, regardless of hemolymph K+ concentration, and K+ cannot displace NH4(+) from its exclusive binding sites. Further, the binding of NH4(+) to its specific sites induces an increase in enzyme apparent affinity for K+, which may contribute to maintaining K+ transport, assuring that exposure to elevated ammonia concentrations does not lead to a decrease in intracellular potassium levels. This is the first report of modulation by ammonium ions of C. ornatus gill (Na+, K+)-ATPase, and should further our understanding of NH4(+) excretion in benthic crabs. PMID- 17276115 TI - Sex and seasonal co-variation of arginine vasotocin (AVT) and gonadotropin releasing hormone (GnRH) neurons in the brain of the halfspotted goby. AB - Gonadotropin-releasing hormone (GnRH) and arginine vasotocin (AVT) are critical regulators of reproductive behaviors that exhibit tremendous plasticity, but co variation in discrete GnRH and AVT neuron populations among sex and season are only partially described in fishes. We used immunocytochemistry to examine sexual and temporal variations in neuron number and size in three GnRH and AVT cell groups in relation to reproductive activities in the halfspotted goby (Asterropteryx semipunctata). GnRH-immunoreactive (-ir) somata occur in the terminal nerve, preoptic area, and midbrain tegmentum, and AVT-ir somata within parvocellular, magnocellular, and gigantocellular regions of the preoptic area. Sex differences were found among all GnRH and AVT cell groups, but were time period dependent. Seasonal variations also occurred in all GnRH and AVT cell groups, with coincident elevations most prominent in females during the peak- and non-spawning periods. Sex and temporal variability in neuropeptide-containing neurons are correlated with the goby's seasonally-transient reproductive physiology, social interactions, territoriality and parental care. Morphological examination of GnRH and AVT neuron subgroups within a single time period provides detailed information on their activities among sexes, whereas seasonal comparisons provide a fine temporal sequence to interpret the proximate control of reproduction and the evolution of social behavior. PMID- 17276117 TI - Natural organic matter (NOM) has the potential to modify the multixenobiotic resistance (MXR) activity in freshwater amphipods Eulimnogammarus cyaneus and E. verrucosus. AB - Based on the chemical features of natural organic matter (NOM) with its variety of functional groups, we hypothesized that NOM will modify the multixenobiotic resistance (MXR) of an organism as xenobiotic chemicals do. The MXR system is a general first rather non-specific line of defense against environmental contaminants. The aim of this study was to compare the impacts on MXR activity in amphipod species (Eulimnogammarus cyaneus and E. verrucosus, from Lake Baikal) stressed by cadmium chloride or dissolved NOM for 24 h. NOM exposure concentrations were environmentally realistic. MXR activity was assessed based on rhodamine B efflux; its specificity was proven by a verapamil inhibition assay. It was shown that both NOM and CdCl(2) lead to substantial reduction of the rhodamine B efflux. This suggests that NOM may be regarded as a chemosensor which is able to reduce the efficiency of the MXR system. Possible mechanisms of direct NOM impact on MXR processes are discussed, such as peroxidation of the membranes (including P-glycoproteins) or internal blockage of the MXR pump by bioconcentrated NOM. In general, our results show that well-developed depuration pathways of freshwater organisms in contaminated environments may be impaired by strong chemical stressors and, more important, by natural biogeochemical matrices such as humic substances--humic substances are present in all freshwater systems. PMID- 17276116 TI - Maternal effects, maternal body size and offspring energetics: a study in the common woodlouse Porcellio laevis. AB - What are the consequences of the natural variation in maternal body mass on offspring energetic performance? How are performance traits related to thermal physiology and energetics phenotypically integrated on offspring? To answer these questions, fifty breeding pairs of the common terrestrial isopod Porcellio laevis were set up in the lab. Physiological performance, thermal tolerance and thermal sensitivity were measured in F1 adults. Maternal effects were estimated as: the direct influence of maternal body mass and the variation associated with mothers. Phenotypic integration was evaluated using path analysis. Our results show that: (1) maternal body size affects positively offspring long-term metabolism, (2) maternal variation was significant in many of the physiological traits and (3) there is an intricate set of relationships among traits and importantly, that offspring exhibited compensational strategies among metabolism, thermal sensitivity and thermal tolerance traits. Even if we cannot clearly state whether these maternal influences were because of the genes or the environment that mothers provided and thus no predictions can be done regarding their evolutionary consequences, it seems clear that the role of maternal effects on physiology can no longer be ignored. In this sense, there's a lot to be gained by incorporating explicit experimental protocols to test for maternal effects. PMID- 17276118 TI - Comparison of fatty acid profiles of spawning and non-spawning Pacific herring, Clupea harengus pallasi. AB - Crude lipid and fatty acid composition from liver, intestine, roe, milt and flesh of spawning and non-spawning Pacific herring (Clupea harengus pallasi) were examined to determine the relative effects of spawning on the nutritional value of herring. Depletion of lipid due to spawning condition was significant (P<0.01) in all organ tissues and flesh of spawning herring. The lipid content ranged from an average of 1.9 to 3.4% (wet weight basis) in different organ tissues of spawning herring, to 10.5 to 16% in non-spawning fish. The fatty acid profile exhibited many differences in the relative distribution of individual fatty acids among organ tissues and between the two fish groups. Oleic acid (C18:1n-9), a major monounsaturated fatty acid (MUFA) found in all tissue lipids, decreased significantly (P<0.01) in spawning fish. The two monoenes, C20:1n-9 and C22:1n 11, occurred at high concentrations in the flesh but at only minor proportion in the digestive organs and gonads. Spawning herring also had significantly (P<0.01) higher polyunsaturated fatty acids (PUFA) content in the organ tissues, particularly in the milt and ovary, with docosahexaenoic acid (C22:6n-3, DHA) having the greatest proportion. Among the n-6 fatty acids, only C18:2n-6 and C20:4n-6 occurred at notable amounts and were present in higher proportions in spawning fish. We concluded that although relatively higher n-3 fatty acid content was found in the organ lipids of spawning herring, they are not an energy dense prey food source due to the fact that both flesh and gonads contain a very low amount of lipid. PMID- 17276119 TI - Maternal and dietary carotenoids interactively affect cutaneous basophil responses in growing chickens (Gallus gallus domesticus). AB - This trial examined effects of lutein supplied from maternal (i.e., in ovo) and dietary routes on cutaneous basophil hypersensitivity responses in chickens. Chicks hatched from one of two in ovo carotenoid levels (n=100/level; carotenoid replete or carotenoid-deplete eggs) were fed one of two diet lutein levels (0 or 40 mg diet lutein/kg diet). At 14 d post-hatch, phytohemagglutinin (PHA) was injected into the wing web, and thickness and leukocyte populations were measured at 0 to 48 h. PHA increased wing web thickness at 4 to 48 h post-PHA (p<0.05), and the swelling response was most related to macrophage numbers in the wing web. Swelling occurred more rapidly in chicks from carotenoid-deplete eggs (p<0.05), but eventually reached a greater thickness in chicks from carotenoid-replete eggs (p<0.05). Differences in leukocyte infiltration occurred due to diet and in ovo carotenoid exposure, and indicate that pre- and post-hatch carotenoid exposure had additive or synergistic effects on the PHA-induced wing web response. Evaluation of the cellular contents of the injection site is a much better indicator of the immunomodulatory effects of lutein than measurements of the amount of swelling. PMID- 17276121 TI - Idiopathic hypertrophic osteopathy in a cat. PMID- 17276120 TI - Effect of cobalt ions on the metabolism of some volatile and polar compounds in the marine invertebrates Mytilus galloprovincialis and Actinia equina. AB - The compositions of the volatile and polar fractions from two coexisting Black Sea invertebrates, the mussel Mytilus galloprovincialis and the beadlet anemone Actinia equina, were established. The main metabolites in the volatile fraction from the investigated animals appeared to be methyl esters of fatty acids and fatty aldehydes. In the polar fraction from both animals low concentrations of free acids and nitrogen-containing compounds were obtained. Free carbohydrates were in much higher concentrations in M. galloprovincialis than in A. equina. Some sterols, probably as polar conjugates, were identified mainly in A. equina. Significant changes among all compounds appeared after treatment of both invertebrates with two different concentrations of cobalt ions. The variety of changes in each invertebrate could be due to their different evolutionary status. The effect of cobalt ions was often stronger at medium cobalt-ion concentrations. PMID- 17276123 TI - Prevalence of Rickettsia felis DNA in the blood of cats and their fleas in the United States. AB - Rickettsia felis is associated with fever, headache, myalgia, and macular rash in some infected humans and has been detected in the cat flea (Ctenocephalides felis) in many countries around the world. While some naturally exposed cats have been assessed for antibodies against R felis, to our knowledge, no one has reported use of polymerase chain reaction (PCR) to attempt to amplify R felis DNA from client-owned cats and the fleas collected from them. In this study, we assayed 92 pairs of cat blood and flea extracts from Alabama, Maryland and Texas, using PCR assays that amplify a region of the citrate synthase gene (gltA) and the outer membrane protein B gene (ompB). Of the 92 pairs, 62 of 92 (67.4%) flea extracts and none of the cat blood samples were positive for R felis DNA. PMID- 17276124 TI - [Leptin in pregnancy: facts, questions and future]. AB - Leptin has been primarily considered as a protein secreted by the adipocyte and a regulator of satiety and energy homeostasis. A role for leptin in pregnancy was later suggested as circulating levels of leptin are high in the pregnant woman and leptin is synthetized within the placenta. Placental leptin production is increased in various obstetrical conditions associated with alterations of fetal growth (diabetes, preeclampsia). Furthermore, umbilical leptin can be viewed as a biomarker of fetal adiposity. Our aim is to review the putative roles of leptin in pregnancy. PMID- 17276125 TI - Forensic aspects of complications resulting from cardiopulmonary resuscitation. AB - While cardiopulmonary resuscitation (CPR) can save lives, it can also injure patients. As a result, forensic pathologists often see CPR-related injuries during autopsies that are unrelated to the patients' primary cause of death. Therefore, pathologists must be able to distinguish between CPR-related injuries and those caused by other factors, such as assaults or accidental violence. This distinction is complicated because even therapeutically unimportant injuries can have forensic significance. For example, resuscitative injuries are observed frequently in the neck and the chest. This article focuses mainly on complications due to ventilation and chest compression during CPR. The following iatrogenic complications are described: bruising and abrasions in the face and neck, fractures of the hyoid bone and thyroid cartilage, air way injuries, vomitus aspiration, positional error of the tube for intra-tracheal intubation, petechiae, retinal hemorrhages, subarachnoid hemorrhages, rib and sternum fractures, bone marrow embolism, cardiac injuries including myocardial hemorrhages and frothy heart blood, and injuries to the abdominal organs such as liver and spleen. PMID- 17276126 TI - Abusive head injuries in infants and young children. AB - Abusive head injuries are among the most common causes of serious and lethal injuries in children. These injuries may result from impact or shaking or a combination of these mechanisms. These mechanisms cause the child's head to undergo acceleration-deceleration movements which may create inertial movement of the brain within the cranial compartment. Differential movement between the brain and skull may result in subdural and subarachnoid hemorrhages and traumatic diffuse axonal injury. This paper will discuss the unique anatomical and developmental features of the immature brain, skull, and neck which render young children particularly vulnerable to shearing injuries, the pathology of those injuries, and the mechanisms of these injuries. PMID- 17276127 TI - Restraint asphyxia in in-custody deaths Medical examiner's role in prevention of deaths. AB - In the United States, the office of the Medical Examiner-Coroner is responsible for investigating all sudden and unexpected deaths and deaths by violence. Its jurisdiction includes deaths during the arrest procedures and deaths in police custody. Police officers are sometimes required to subdue and restrain an individual who is violent, often irrational and resisting arrest. This procedure may cause harm to the subject and to the arresting officers. This article deals with our experiences in Los Angeles and reviews the policies and procedures for investigating and determining the cause and manner of death in such cases. We have taken a "quality improvement approach" to the study of these deaths due to restraint asphyxia and related officer involved deaths, Since 1999, through interagency coordination with law enforcement agencies similar to the hospital healthcare quality improvement meeting program, detailed information related to the sequence of events in these cases and ideas for improvements to prevent such deaths are discussed. PMID- 17276128 TI - Treatment of dye wastewater by using photo-catalytic oxidation with sonication. AB - The degradation of Acid Orange 52 in aqueous solutions was investigated by using three processes (photocatalysis, sonolysis, and photocatalysis with sonication). In the case of photocatalysis, although the concentration of Acid Orange 52 decreased to 35% in 480 min, the color of the solution was not disappeared. In the case of sonolysis, it was decomposed completely in 300 min, but the total organic carbon concentration decreased down by only about 13% in 480 min. In the case of photocatalysis with sonication, the concentration of Acid Orange 52 reached to 0 in 240 min and the total organic carbon concentration decreased by about 87% in 480 min. These results indicate that the ultrasonic irradiation enhanced the photocatalytic degradation. The addition of chloride ion (50 ppm) into Acid Orange 52 solution decreased the decomposition efficiency for photocatalysis. In the cases of sonolysis and photocatalysis with sonication, the decomposition efficiency did not change significantly by the addition of chloride ion. These results indicate that chloride ion disturbs the photocatalysis of dye, but the decomposition of dye using the irradiation of ultrasound is not influenced by chloride ion. From these results, it is considered that the photocatalysis with sonication is most effective for the decomposition of dye in the three processes in this study. PMID- 17276129 TI - Epsin: inducing membrane curvature. AB - Epsin was originally discovered by virtue of its binding to another accessory protein, Eps15. Members of the epsin family play an important role as accessory proteins in clathrin-mediated endocytosis. Epsin isoforms have been described that differ in intracellular site of action and/or in tissue distribution, although all epsins essentially contribute to membrane deformation. Besides inducing membrane curvature, epsin also plays a key function as adaptor protein, coupling various components of the clathrin-assisted uptake and fulfils an important role in selecting and recognizing cargo. Furthermore, epsin possesses the ability to block vesicle formation during mitosis. To perform all these functions, epsin, apart from interacting with PtdIns(4,5)P2 via its ENTH domain, also engages in several protein interactions with different components of the clathrin-mediated endocytic system. Recently, RNA interference has successfully been exploited to generate a cell line constitutively silencing epsin expression, which can be used to study internalization of multiple ligands. PMID- 17276130 TI - Optimal decision-making theories: linking neurobiology with behaviour. AB - This article reviews recently proposed theories postulating that, during simple choices, the brain performs statistically optimal decision making. These theories are ecologically motivated by evolutionary pressures to optimize the speed and accuracy of decisions and to maximize the rate of receiving rewards for correct choices. This article suggests that the models of decision making that are proposed on different levels of abstraction can be linked by virtue of the same optimal computation. Also reviewed here are recent observations that many aspects of the circuit that involves the cortex and basal ganglia are the same as those that are required to perform statistically optimal choice. This review illustrates how optimal-decision theories elucidate current data and provide experimental predictions that concern both neurobiology and behaviour. PMID- 17276131 TI - Attitudes and evaluations: a social cognitive neuroscience perspective. AB - Automatic evaluations are crucial for survival, but conscious self-reflection enables the formulation of nuanced evaluations to serve long-term goals. To operate effectively, both automatic and reflective evaluative processes need to integrate stored representations from previous experience (attitudes) with current contexts and goals, but contexts and goals have a more prominent role in reflective evaluation. Recent neuroimaging data provide new insights into the structure and function of evaluation and the dynamic ways that attitudes and reflective processing contribute to evaluation. In this paper, we propose a new iterative-reprocessing (IR) model of the neural bases of evaluation that highlights the role of the prefrontal cortex in the reprocessing of evaluative information. This model makes predictions that inform social-cognitive and cognitive-neuroscientific accounts of evaluation. PMID- 17276132 TI - New approaches for medicinal applications of bioinorganic chemistry. AB - Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. Today, metal-containing imaging agents and therapeutics constitute a multi-billion dollar industry. Recent discoveries in bioinorganic chemistry of potential biomedical importance include the use of metal ions as synthetic scaffolds for the preparation of small molecule therapeutics, which opens up a new route to molecular structure and diversity, as well as the examination of metal-organic frameworks as biological imaging and drug delivery agents. These areas represent some of the most recent and still relatively unexplored themes in inorganic and bioinorganic chemistry that might be exciting and fruitful topics of study for the community interested in 'metals in medicine'. PMID- 17276133 TI - Heat shock does not induce gammaH2AX foci formation but protects cells from N methyl-N'-nitro-N-nitrosoguanidine-induced genotoxicity. AB - The involvement of DNA damage in heat shock-induced cell death remains controversial. To investigate whether heat shock can induce DNA damage, we tested the induction of gammaH2AX foci formation, a sensitive indicator for DNA double strand breaks (DSBs), by heat shock treatment in several cell lines including HeLa, CHL, HepG2, and 293 cells, as well as human spermatozoa. Although heat shock treatment can decrease cell viability, no induction of gammaH2AX foci formation was observed in any of these cells. In addition, a p53-deficient cell line (U2OSE6tet24) and a flap endonuclease 1 (FEN1)-deficient cell line (FL-FEN1( )) also did not show induction of gammaH2AX foci after heat shock treatment. Finally, it was found that 30min of pre-heat shock can inhibit gammaH2AX foci formation induced by an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which is known to induce gammaH2AX foci formation. On the other hand, heat shock after MNNG treatment did not affect the gammaH2AX foci formation induced by MNNG. Taken together, these data suggest that although heat shock might influence the gammaH2AX foci formation process, it does not induce DNA damage in the cells tested in this study. PMID- 17276134 TI - Protective effect of DCTN (trans-dehydrocrotonin) against induction of micronuclei and apoptosis by different mutagenic agents in vitro. AB - The use of medicinal plants to combat diseases has increased in the last years despite the little information available with regard to the possible health risks they represent. The aim of the present study was to determine in vitro the possible clastogenic, apoptotic and cytotoxic effects of the active principle of Croton cajucara, trans-dehydrocrotonin (DCTN), and determine its protective effect against three mutagenic agents using the micronucleus test (MN) and apoptosis index in CHO-K1 cells. Three DNA damage inducing agents were utilized in the clastogenicity and anticlastogenicity tests (methylmethane sulfonate (MMS), mitomycin C (MMC) and doxorubicin (DXR); a negative control (PBS) and solvent control were also included. DCTN at concentrations of 400, 320, 240, 160 and 80microM did not show clastogenic activity in cultured CHO-K1 cells in the micronucleus test, did not induce apoptosis and showed negligible cytotoxicity in all cases. DCTN at concentrations of 240 and 400microM was tested for protective activity using three treatment protocols in relation to positive controls: pre treatment, simultaneous treatment and post-treatment. The micronucleus test showed a protective effect for DCTN which varied among the different treatment protocols and with regard to the different DNA damage inducing agents. In the apoptosis test, DCTN was seen to have a protective effect under the following conditions: (I) at both concentrations in relation to MMS, in all three treatment protocols; (II) at both concentrations against damage caused by MMC with pre treatment and at the higher concentration with simultaneous treatment; (III) at both concentrations against DXR with simultaneous treatment. Therefore, DCTN itself is not a clastogenic or cytotoxic substance, and does not induce apoptosis the in vitro system used. These results together with findings reported for DCTN in vivo, support the indication of this active principle at these concentrations for therapeutic use. PMID- 17276135 TI - Molecular characterization of a variant rhinovirus from an outbreak associated with uncommonly high mortality. AB - BACKGROUND: Human rhinoviruses (HRVs) are the most frequent cause of acute upper respiratory tract infection, however, they are also known to replicate in the lower respiratory tract and associate with more severe respiratory illnesses. An outbreak of HRV occurred in a long-term facility in Santa Cruz, California with unusually high morbidity and mortality. OBJECTIVES: To identify viral characteristics associated with this unique outbreak, genetic relationships between these clinical isolates (SCRVs) and prototype strains of rhinovirus were investigated. STUDY DESIGN: Sequence homology and phylogenetic analyses of the SCRV VP4/VP2 region were performed in conjunction with all HRV prototypes. Due to the importance of the 5'noncoding region (NCR) and the structural genes to viral replication and host immune responses, respectively, we focused on a segment of the HRV genome which includes these regions. Molecular models of SCRV were also assessed. RESULTS: SCRV showed closest similarity to HRV82 with some divergence from the prototype. Amino acid differences were concentrated within predicted neutralization epitopes within VP2, VP3 and VP1. CONCLUSION: Sequence analyses and differences in cell culture growth characteristics suggest that this virus is a variant of HRV which has distinctive properties from its respective prototype strain. PMID- 17276136 TI - Flagellar and global gene regulation in Helicobacter pylori modulated by changes in DNA supercoiling. AB - In Helicobacter pylori, a host-adapted bacterium with a small genome and few dedicated transcriptional regulators, promoter structure, and gene organization suggested a role for DNA topology in the transcriptional regulation of flagellar genes. H. pylori DNA supercoiling, monitored by a reporter plasmid, was relaxed by novobiocin, an inhibitor of DNA gyrase. A decrease in negative supercoiling coincided with lowered transcription of the late flagellin gene flaA. Targeted mutagenesis that either increased or decreased promoter spacer length in the flaA sigma(28) promoter lowered flaA transcript levels, expression of FlaA protein, and flagella formation. It also changed the promoter response to decreased superhelicity. Supercoiling of reporter plasmid DNA in H. pylori varied with growth phase in liquid culture. H. pylori sigma(28) promoters of various spacer length, as well as other supercoiling-sensitive genes, were differentially transcribed during the growth phases, consistent with supercoiling being associated with growth phase regulation. Genome-wide transcript analysis of wild type H. pylori under conditions of reduced supercoiling identified flagellar, housekeeping, and virulence genes, the expression of which correlated with supercoiling change and/or growth phase. These data indicate that global supercoiling changes may help coordinate temporal (growth phase-related) regulation of flagellar biosynthesis and other cellular functions in Helicobacter. PMID- 17276137 TI - Cancer care in Spain. PMID- 17276138 TI - Astrocytes are active players in cerebral innate immunity. AB - Innate immunity is a constitutive component of the central nervous system (CNS) and relies strongly on resident myeloid cells, the microglia. However, evidence is emerging that the most abundant glial cell population of the CNS, the astrocyte, participates in the local innate immune response triggered by a variety of insults. Astrocytes display an array of receptors involved in innate immunity, including Toll-like receptors, nucleotide-binding oligomerization domains, double-stranded RNA-dependent protein kinase, scavenger receptors, mannose receptor and components of the complement system. Following activation, astrocytes are endowed with the ability to secrete soluble mediators, such as CXCL10, CCL2, interleukin-6 and BAFF, which have an impact on both innate and adaptive immune responses. The role of astrocytes in inflammation and tissue repair is elaborated by recent in vivo studies employing cell-type specific gene targeting. PMID- 17276139 TI - RNA interference in parasitic nematodes of animals: a reality check? AB - RNA interference (RNAi) is widely used in Caenorhabditis elegans to identify gene function and has been adapted as a high-throughput screening method to identify genes involved in essential processes. The technique has been applied to parasitic nematodes with variable success and we believe that inconsistent outcomes preclude its use as a robust screen with which to identify potential control targets. In this article, key issues that require clarification are discussed, including the mode of delivery of double-stranded RNA to the parasite, the developmental stage targeted and, perhaps of most importance, whether the RNAi pathway (as defined by studies in C. elegans) is fully functional in some parasitic nematodes. PMID- 17276141 TI - Interferon-gamma gene+874T-A polymorphism is associated with tuberculosis and gamma interferon response. AB - Interferon-gamma is the most important cytokine in resistance to mycobacterial diseases and common variants of interferon-gamma gene could be related to tuberculosis susceptibility. We tested the hypothesis that the interferon gamma+874T-A polymorphism is associated with tuberculosis disease, and affects the interferon-gamma response. We determined by pyrosequencing the distribution of the interferon-gamma+874T-A polymorphism in a Turkish population of 319 patients with pulmonary tuberculosis, 42 children with severe forms of tuberculosis and 115 healthy donors. We also analysed whether any correlation exists between this polymorphism and interferon-gamma response to Mycobacterium tuberculosis antigens by ELISPOT in 58 pulmonary tuberculosis cases, and the results were analysed according to the genotypes. We found that the minor allele (T) frequency was significantly lower in patients with pulmonary tuberculosis when compared to controls (P=0.024, OR=0.7), a similarly significant decrease in the frequency of TT genotype was observed in patients with pulmonary tuberculosis, compared to the control group (P=0.02, OR=0.49). IFN-gamma responses to PPD antigen in TT genotype was found to be significantly higher than the AA group (P>0.001). Non-parametric correlation analysis of ELISPOT data showed significant reverse correlation in PPD, CFP10 and ESAT6 values and IFN gamma +874 genotypes. These results show that the IFN-gamma +874T-A polymorphism is related to the IFN-gamma response and the magnitude of the response decreases during transition from TT- to TA and to AA genotypes. Our data suggest that similar to various Caucasian populations, in a Turkish population the IFN gamma+874 T-A polymorphism is also associated with tuberculosis disease and affects the magnitude of the IFN-gamma response. PMID- 17276140 TI - Vitamin and cofactor biosynthesis pathways in Plasmodium and other apicomplexan parasites. AB - Vitamins are essential components of the human diet. By contrast, the malaria parasite Plasmodium falciparum and related apicomplexan parasites synthesize certain vitamins de novo, either completely or in parts. The various biosynthesis pathways are specific to different apicomplexan parasites and emphasize the distinct requirements of these parasites for nutrients and growth factors. The absence of vitamin biosynthesis in humans implies that inhibition of the parasite pathways might be a way to interfere specifically with parasite development. However, the roles of biosynthesis and uptake of vitamins in the regulation of vitamin homeostasis in parasites needs to be established first. In this article, the procurement of vitamins B(1), B(5) and B(6) by Plasmodium and other apicomplexan parasites is discussed. PMID- 17276143 TI - Conflict about expressing emotions and chronic low back pain: associations with pain and anger. AB - There has been growing interest among researchers and clinicians in the role of ambivalence over emotional expression (AEE) in adjustment to chronic illness. Because of the salience of anger in chronic low back pain, this condition provides a particularly good model in which to examine the role of AEE. This study examined the relation of AEE to pain and anger in a sample of 61 patients with chronic low back pain. Patients completed standardized measures of AEE, pain, and anger. Correlational analyses showed that patients who had higher AEE scores reported higher levels of evaluative and affective pain as well as higher levels of state and trait anger and the tendency to hold in angry thoughts and feelings. Mediational analyses revealed that most of the associations between AEE and pain, and AEE and anger, were independent of one another. These findings suggest that a potentially important relationship exists between AEE and key aspects of living with persistent pain. PERSPECTIVE: This preliminary study suggests that there is a relation between ambivalence over emotional expression and pain and anger in patients with chronic low back pain. Patients who report greater conflict with regard to expressing emotions may be experiencing higher pain and anger. PMID- 17276142 TI - Update on multi-center clinical trials in the United States. AB - This article reviews numerous multi-center clinical trials, either ongoing or in planning stages, which involve diverse clinical applications and emerging technologies in apheresis and transfusion medicine. The investigations summarized herein involve the following specific areas: platelet dosing strategy, thrombotic thrombocytopenia purpura, inflammatory bowel disease, seven-day platelet storage, dendritic cell vaccines, and age-related macular degeneration. PMID- 17276144 TI - Is the latent structure of fear of pain continuous or discontinuous among pain patients? Taxometric analysis of the pain anxiety symptoms scale. AB - Elevated fear of pain is believed to denote a potential mechanism through which pain is maintained over time; however, our knowledge about fear of pain, its measurement, and its conceptualization is far from complete. It has been assumed that the latent structure of fear of pain is multidimensional and continuous. Although there is factor analytic evidence that it is multidimensional, there have been no empiric efforts to establish whether fear of pain is continuous or discontinuous (ie, taxonic or dichotomous latent class variable) in nature. Using taxometric methods in a sample of 650 patients seeking treatment for musculoskeletal or headache pain, we evaluated the latent structure of fear of pain as indexed by the Pain Anxiety Symptoms Scale. Results from analyses of simulated Monte Carlo data, MAXEIG-HITMAX, and MAMBAC and L-mode external consistency tests indicated that the latent structure of fear of pain was nontaxonic, characterized by latent continuity. Results are discussed in relation to the conceptual understanding of fear of pain, implications for treatment, and future directions for research on issues pertinent to pain-related fear. PERSPECTIVE: This article presents an analysis designed to establish whether fear of pain is continuous or discontinuous in clinical samples. The findings, indicating that fear of pain is continuous, are important for understanding the nature of fear of pain and to designing appropriately targeted interventions. PMID- 17276145 TI - Runtime application of Hybrid-Asbru clinical guidelines. AB - Clinical guidelines are a major tool in improving the quality of medical care. However, to support the automation of guideline-based care, several requirements must be filled, such as specification of the guidelines in a machine interpretable format and a connection to an Electronic Patient Record (EPR). For several different reasons, it is beneficial to convert free-text guidelines gradually, through several intermediate representations, to a machine interpretable format. It is also realistic to consider the case when an EPR is unavailable. We propose an innovative approach to the runtime application of intermediate-represented Hybrid-Asbru guidelines, with or without an available EPR. The new approach capitalizes on our extensive work on developing the Digital electronic Guideline Library (DeGeL) framework. The new approach was implemented as the Spock system. For evaluation, three guidelines were specified in an intermediate format and were applied to a set of simulated patient records designed to cover prototypical cases. In all cases, the Spock system produced the expected output, and did not produce an unexpected one. Thus, we have demonstrated the capability of the Spock system to apply guidelines encoded in the Hybrid-Asbru intermediate representation, when an EPR is not available. PMID- 17276146 TI - Spontaneous awakening from nocturnal sleep and cardiac autonomic function in preschool children. AB - A cross-sectional study was carried out to clarify the physiological features of spontaneous awakening from nocturnal sleep (i.e., whether a child can spontaneously wake up on weekday mornings). The study population comprised 116 children at ages 5 and 6 years. Heart rate variability reflecting cardiac sympathetic and parasympathetic activities was measured. Children's typical bedtimes and wake times for weekdays and the presence/absence of spontaneous awakening from nocturnal sleep were reported by parents, and information about obligatory naptimes was provided by preschool teachers. The mean total sleep duration in the children was 625+/-56 (standard deviation) min. Total and nocturnal sleep durations were significantly shorter in 52 children without spontaneous awakening than in 64 children with it. Similarly, the parasympathetic activity was significantly lower in the children without spontaneous awakening, even in using analysis of covariance. Heart rate was significantly increased in the children without spontaneous awakening, but neither total nor nocturnal sleep durations were significant covariates in the analysis of covariance. In conclusion, the absence of spontaneous awakening from nocturnal sleep in preschool children is suggested to be characterized by short sleep duration, parasympathetic hypoactivity, and elevated heart rate. PMID- 17276147 TI - Population pharmacokinetics of tobramycin administered thrice daily and once daily in children and adults with cystic fibrosis. AB - BACKGROUND: Tobramycin pharmacokinetics have not been evaluated previously in a large series of data collected in children and adults with CF receiving once (OD) or three times daily (TD) tobramycin. METHODS: Therapeutic drug monitoring data in children and adults with CF who participated in a randomised clinical trial evaluating efficacy and toxicity of OD versus TD tobramycin (TOPIC study) were analysed retrospectively. Population pharmacokinetic models stratified to treatment schedule were created, and individual pharmacokinetic parameters were calculated. RESULTS: In paediatric patients, volume of distribution per kg body weight (V1) was greater with OD treatment compared to TD (0.401+/-0.092 versus 0.354+/-0.041, p=0.003). Elimination rate was reduced in all patients receiving OD tobramycin compared to TD (children: 0.00197+/-0.00027 versus 0.00291+/ 0.00041, p<0.001, adults: 0.00252+/-0.00008 versus 0.00322+/-0.00050, p<0.001). Tobramycin V1 decreased with increasing age (R(2)=0.3, p<0.001). CONCLUSIONS: The reduced elimination rate in OD may either be caused by circadian pharmacokinetic behaviour of tobramycin or indicates early renal damage caused by high tobramycin doses not detected by biochemical measurements. However, results of our previous work suggest that OD tobramycin may be less nephrotoxic. The higher V1 in children implies that a relative higher tobramycin dose in these patients is needed for the same target peak serum concentration. PMID- 17276148 TI - Does repeated disinfection of the e-Flow rapid nebulizer affect in vitro performance? AB - Repeated disinfection of a nebulizer may modify its performance. During 60 cycles of disinfection with the Nuk steam sterilizer (120 nebulizations), the median volume diameter of tobramycin or colistin, nebulization time and various parameters correlated with the membrane weight of the e-Flow rapid are not modified. Results are similar when tap or purified water is used for washing and disinfection. PMID- 17276149 TI - Is ATP a suitable co-transmitter in carotid body arterial chemoreceptors? AB - A review is presented on carotid body ATP content, effects and release, receptors involved and results of their block by purinergic antagonists, and the possibility of cholinergic-purinergic co-transmission in the carotid body. Glomus cells release ACh and ATP upon physiological stimulation. Both agents and their agonists have chemo-excitatory actions and their combined effects disappear upon blocking n-ACh and P2X receptors. Both ACh and ATP also are capable of exciting the somata of chemosensory neurons of petrosal ganglia. Although a combined cholinergic-purinergic block suppresses the chemosensory activity in neurons co cultured with glomus cells and some carotid body preparations in vitro, basal chemosensory activity and chemosensory responses to hypoxic stimuli persist in cat carotid body preparations in situ and in vitro. Therefore, ATP is an effective excitatory agent for carotid body chemosensory activity, although less potent than ACh; their joint participation may contribute to -- but does not entirely explain -- the transfer of chemoreceptor excitation from glomus cells to sensory endings in carotid body. PMID- 17276152 TI - Isolated infiltrative endometriosis of the sciatic nerve: a report of three patients. AB - OBJECTIVE: To report that isolated endometriosis of the sciatic nerve without further manifestation of endometriosis does exist. DESIGN: We describe our technique of laparoscopic neurolysis of the sciatic nerve and the sacral plexus. SETTING: Department of Gynecology and Obstetrics, St. Elisabeth Hospital, affiliated with the University of Cologne, Cologne, Germany. PATIENT(S): Three female patients with isolated endometriotic infiltration of the endopelvic portion of the sciatic nerve. INTERVENTION(S): Elective laparoscopic neurolysis of the sciatic nerve with removal of endometriosis. MAIN OUTCOME MEASURE(S): Disparition of pain in the patients and histologic information of the endometriosis. RESULT(S): Isolated endometriosis of the sciatic nerve and/or the sacral plexus does exist without any further endometriosis genitalis externa manifestations. CONCLUSION(S): In young patients with sciatica of an unknown genesis, an endometriosis of the sciatic nerve must be evoked, and a laparoscopic exploration of the sciatic nerve must be discussed. PMID- 17276151 TI - Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression. AB - Mesenchymal stromal cells (MSCs) seeded onto biocompatible scaffolds have been proposed for repairing bone defects. When transplanted in vivo, MSCs (expanded in vitro in 21% O(2)) undergo temporary oxygen deprivation due to the lack of pre existing blood vessels within these scaffolds. In the present study, the effects of temporary (48 h) exposure to hypoxia ( or = 1.0 cm2; mean age 73.7 +/- 8.9 years; 57 men and 64 women), treated with and without rosuvastatin according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Echocardiographic, serum lipid, and inflammatory markers were measured at baseline and every 6 months for 18 months. RESULTS: Sixty-one patients (50.4%) with elevated LDL (159.7 +/- 33.4 mg/dl), aortic valve velocity (3.65 +/- 0.64 m/s), and aortic valve area (1.23 +/- 0.42 cm2) received rosuvastatin (20 mg/day), and 60 (49.6%) with a normal LDL (118.6 +/- 37.4 mg/dl), aortic valve velocity (3.62 +/- 0.61 m/s), and aortic valve area (1.20 +/- 0.35 cm2) received no statin. During a mean follow-up of 73 +/- 24 weeks, the change in aortic valve area in the control group was -0.10 +/- 0.09 cm2/year versus -0.05 +/- 0.12 cm2/year in the rosuvastatin group (p = 0.041). The increase in aortic valve velocity was 0.24 +/- 0.30 m/s/year in the control group and 0.04 +/- 0.38 m/s/year in the rosuvastatin group (p = 0.007). There was significant improvement in serum lipid and echocardiographic measures of aortic stenosis in the statin group. CONCLUSIONS: Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the hemodynamic progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process. (Rosuvastatin Affecting Aortic Valve Endothelium; http://www.clinicaltrials.gov/ct/show/NCT00114491?order = 1; NCT0014491). PMID- 17276180 TI - Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. AB - OBJECTIVES: This study sought to identify whether obesity and obstructive sleep apnea (OSA) independently predict incident atrial fibrillation/flutter (AF). BACKGROUND: Obesity is a risk factor for AF, and OSA is highly prevalent in obesity. Obstructive sleep apnea is associated with AF, but it is unknown whether OSA predicts new-onset AF independently of obesity. METHODS: We conducted a retrospective cohort study of 3,542 Olmsted County adults without past or current AF who were referred for an initial diagnostic polysomnogram from 1987 to 2003. New-onset AF was assessed and confirmed by electrocardiography during a mean follow-up of 4.7 years. RESULTS: Incident AF occurred in 133 subjects (cumulative probability 14%, 95% confidence interval [CI] 9% to 19%). Univariate predictors of AF were age, male gender, hypertension, coronary artery disease, heart failure, smoking, body mass index, OSA (hazard ratio 2.18, 95% CI 1.34 to 3.54) and multiple measures of OSA severity. In subjects <65 years old, independent predictors of incident AF were age, male gender, coronary artery disease, body mass index (per 1 kg/m2, hazard ratio 1.07, 95% CI 1.05 to 1.10), and the decrease in nocturnal oxygen saturation (per 0.5 U log change, hazard ratio 3.29, 95% CI 1.35 to 8.04). Heart failure, but neither obesity nor OSA, predicted incident AF in subjects > or =65 years of age. CONCLUSIONS: Obesity and the magnitude of nocturnal oxygen desaturation, which is an important pathophysiological consequence of OSA, are independent risk factors for incident AF in individuals <65 years of age. PMID- 17276181 TI - Gender-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe: a report from the Euro Heart Survey on Atrial Fibrillation. AB - OBJECTIVES: This study sought to investigate gender-related differences in patients with atrial fibrillation (AF) in Europe. BACKGROUND: Gender-related differences may play a significant role in AF. METHODS: We analyzed the data of 5,333 patients (42% female) enrolled in the Euro Heart Survey on Atrial Fibrillation. RESULTS: Compared with men, the women were older, had a lower quality of life (QoL), had more comorbidities, more often had heart failure (HF) with preserved left ventricular systolic function (18% vs. 7%, p < 0.001), and less often had HF with systolic dysfunction (17% vs. 26%, p < 0.001). Among patients with typical AF symptoms (56% of women, 49% of men), there was no gender related difference in the choice of rate or rhythm control. Among patients with atypical or no symptoms (44% of women, 51% of men), women less frequently underwent rhythm control (39% vs. 51%, p < 0.001) than did men. Women underwent less electrical cardioversion (22% vs. 28%, p < 0.001). Prescription of oral anticoagulants was identical (65%) in both genders. One-year outcome was similar except that women had a higher chance for stroke (odds ratio 1.83 in multivariable regression analysis, p = 0.019). CONCLUSIONS: Women with AF had more comorbidities, more HF with preserved systolic function, and a lower QoL than men. In the large group with atypical or no symptoms, women were treated appropriately more conservatively with less rhythm control than men. Women had a higher chance for stroke. Long-term QoL changes and other morbidities and mortality were similar. PMID- 17276182 TI - Stretch-sensitive KCNQ1 mutation A link between genetic and environmental factors in the pathogenesis of atrial fibrillation? AB - OBJECTIVES: This study sought to evaluate mutations in genes encoding the slow component of the cardiac delayed rectifier K+ current (I(Ks)) channel in familial atrial fibrillation (AF). BACKGROUND: Although AF can have a genetic etiology, links between inherited gene defects and acquired factors such as atrial stretch have not been explored. METHODS: Mutation screening of the KCNQ1, KCNE1, KCNE2, and KCNE3 genes was performed in 50 families with AF. The effects of mutant protein on cardiac I(Ks) activation were evaluated using electrophysiological studies and human atrial action potential modeling. RESULTS: One missense KCNQ1 mutation, R14C, was identified in 1 family with a high prevalence of hypertension. Atrial fibrillation was present only in older individuals who had developed atrial dilation and who were genotype positive. Patch-clamp studies of wild-type or R14C KCNQ1 expressed with KCNE1 in CHO cells showed no statistically significant differences between wild-type and mutant channel kinetics at baseline, or after activation of adenylate cyclase with forskolin. After exposure to hypotonic solution to elicit cell swelling/stretch, mutant channels showed a marked increase in current, a leftward shift in the voltage dependence of activation, altered channel kinetics, and shortening of the modeled atrial action potential duration. CONCLUSIONS: These data suggest that the R14C KCNQ1 mutation alone is insufficient to cause AF. Rather, we suggest a model in which a "second hit", such as an environmental factor like hypertension, which promotes atrial stretch and thereby unmasks an inherited defect in ion channel kinetics (the "first hit"), is required for AF to be manifested. Such a model would also account for the age-related increase in AF development. PMID- 17276183 TI - The prevalence and anatomical patterns of intramuscular coronary arteries: a coronary computed tomography angiographic study. AB - OBJECTIVES: This study sought to report prevalence and radiologic patterns of intramuscular coronary arteries (myocardial bridging) on coronary computed tomographic angiography (CCTA). BACKGROUND: Reported prevalence of intramuscular coronary arteries varies between 5% and 86% in autopsy and 0.8% and 4.9% in coronary angiography. Intramuscular coronary arteries can cause technical problems during coronary bypass surgery, including inadvertent perforation of the right ventricle. METHODS: One hundred and eighteen consecutive patients were studied with CCTA using Brilliance 40/64 multidetector computed tomography (Philips Medical Systems, Cleveland, Ohio). Parameters evaluated were number, length, and depth of intramuscular coronary segments; diameter and evidence of atherosclerosis in the involved artery proximal and within the intramuscular segment; and its course in relation to the interventricular septum and right ventricular wall. RESULTS: Forty-seven intramuscular segments were identified in 36 of 118 (30.5%) patients. Most were located in mid left anterior descending coronary artery (LAD), 27 of 47 (57%), and distal LAD, 7 of 47 (15%). The CCTA features in the LAD showed 3 patterns: superficial septal, 10 of 34 (29.4%); deep septal, 14 of 34 (41.1%); and right ventricular type, 10 of 34 (29.4%). Intramuscular segment length ranged from 13 to 40 mm. Coronary diameter proximal and within the affected segment was 2.2 +/- 0.5 mm versus 1.6 +/- 0.6 mm for the LAD, and 1.9 +/- 0.3 mm versus 1.5 +/- 0.6 mm for the remaining arteries, respectively. Depth ranged from 0.1 to 5.6 mm. CONCLUSIONS: Prevalence of intramuscular coronary arteries on CCTA is in concordance with most pathological reports and higher than in angiographic series. The CCTA clearly showed presence, course, and anatomical features of intramuscular coronary arteries. Coronary computed tomographic angiography may provide potentially useful information in the preoperative evaluation of candidates for coronary bypass surgery. PMID- 17276184 TI - Relationship between C-reactive protein levels and regional left ventricular function in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis. AB - OBJECTIVES: This study sought to investigate the relationship between C-reactive protein (CRP) and regional left ventricular (LV) function in asymptomatic individuals without a history of cardiovascular disease. BACKGROUND: C-reactive protein is associated with an increased risk for developing cardiovascular disease. However, the relationship between CRP and subclinical LV dysfunction has not been evaluated in asymptomatic individuals. METHODS: Regional myocardial function was analyzed as peak systolic circumferential shortening strain (Ecc) using the harmonic-phase method by tagged magnetic resonance imaging in 1,164 individuals without symptomatic cardiovascular disease from the MESA (Multi Ethnic Study of Atherosclerosis) trial (age 66.4 +/- 9.6 years old). Regions were defined by coronary territories: left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). The relationship between log-CRP concentration and Ecc was studied by multivariable linear regression after adjustment for demographic characteristics, risk factors, and therapy (including hormone replacement therapy). RESULTS: For each region, associations differed by gender with no association of CRP and regional LV function among women. In men, after adjustment, higher log-CRP was significantly associated with lower (absolute) Ecc in the LAD and RCA regions (regression coefficient 0.37 per unit higher log-CRP [95% confidence interval [CI] 0.08 to 0.65] and 0.31 [95% CI 0.02 to 0.59], respectively) and peak systolic Ecc overall (regression coefficient 0.32 [95% CI 0.05 to 0.58]). In the LCX region, the association was weaker (p = 0.06). CONCLUSIONS: Among individuals without evident heart failure or other cardiovascular disorders, higher CRP was associated with lower systolic myocardial function in all regions in men but not in women. These findings support the role of inflammation and atherosclerosis in incipient myocardial dysfunction. (Multi-Ethnic Study of Atherosclerosis; http://clinicaltrials.gov/ct/show/NCT00005487). PMID- 17276185 TI - Total liquid ventilation provides ultra-fast cardioprotective cooling. AB - OBJECTIVES: We tested whether total liquid ventilation (TLV) can be used to rapidly cool and protect the infarcting heart. BACKGROUND: Decreasing myocardial temperature during ischemia is a powerful cardioprotective strategy, but clinical application has been impaired by lack of practical methodology to quickly cool the heart. METHODS: We performed 30-min coronary artery occlusion/3-h reperfusion in rabbits. Upon occlusion, rabbits underwent either oxygen (Gas), normothermic liquid (Liquid Warm), or cold liquid (Liquid Cool) ventilation. RESULTS: Left atrial chamber temperature decreased to 32.4 degrees +/- 0.2 degrees C within 5 min of onset of cold TLV. Blood gases were within acceptable limits during TLV. In the Liquid Warm group, perfluorocarbon inhalation did not alter infarct size compared with Gas (37.7 +/- 1.3% and 42.5 +/- 4.9% of risk zone, respectively). However, infarction was significantly reduced in the Liquid Cool group (4.0 +/- 0.5%). Cooling only during the initial 30 min of reperfusion did not reduce infarction. CONCLUSIONS: Total liquid ventilation can elicit rapid cardioprotective cooling during ischemia. PMID- 17276186 TI - A cool heart protected from infarction: clinical translation of breathing chilled liquids. PMID- 17276187 TI - Highlights of the 2006 scientific sessions of the Heart Failure Society of America: Seattle, Washington, September 10-13, 2006. PMID- 17276188 TI - Effectiveness of drug-eluting stents in patients with bare-metal in-stent restenosis: meta-analysis of randomized trials. AB - OBJECTIVES: We sought to synthesize the available evidence on the effectiveness of drug-eluting stents for bare-metal in-stent restenosis. BACKGROUND: Although there is clinical evidence that drug-eluting stents are associated with better results than other treatments for in-stent restenosis, they are not yet approved for this indication. Meta-analysis of randomized trials may yield more precise estimates of treatment effects and enable a rapid adoption of effective treatments in clinical practice. METHODS: Data sources included PubMed and conference proceedings. Prespecified criteria were met by 4 randomized studies comparing sirolimus- or paclitaxel-eluting stents versus balloon angioplasty or vascular brachytherapy in 1,230 patients with bare-metal in-stent restenosis. Studies reported the clinical outcomes of efficacy and safety during a minimum of 9 months. The primary outcome was target lesion revascularization. RESULTS: No significant heterogeneity was found across trials, thus showing a similar effect size regardless of the use of balloon angioplasty or vascular brachytherapy as comparators. The risk of target lesion revascularization (odds ratio 0.35, 95% confidence interval [CI] 0.25 to 0.49; p < 0.001) and that of angiographic restenosis (odds ratio 0.36, 95% CI 0.27 to 0.49; p = 0.001) were markedly lower in patients treated with drug-eluting stents. There were no differences between patients treated with drug-eluting stents and those treated with other techniques with respect to the composite of death or myocardial infarction (odds ratio 1.04, 95% CI 0.54 to 2.03; p = 0.55). CONCLUSIONS: Drug-eluting stents are markedly superior to conventional techniques (balloon angioplasty and vascular brachytherapy) and should be considered as first-line treatment for patients with bare-metal in-stent restenosis. PMID- 17276189 TI - President's page: the ACC's international mission: learning, leading, and sharing. PMID- 17276191 TI - The mortality of late stent thrombosis in the drug-eluting stent era--still underemphasized. PMID- 17276192 TI - Platelet dysfunction associated with insulin therapy in patients with type 2 diabetes: please do not throw the baby out with the bathwater! PMID- 17276195 TI - Lessons from the history of wound healing. AB - Despite that most of wound healing history is based on early mysticism, empirical reasoning, and unfounded conclusions, there was a tremendous amount of imagination and brilliance among a few who thought clearly and objectively and were brave enough to defend their new ideas. As we enter the 21st century, new laboratory tools have led us to gather a tremendous amount of scientific data as to the biological events of healing. Surprisingly, this new knowledge has not led to many "breakthroughs" in our management of wounds and scars. Although much has been accomplished, the pieces have yet to be fit together in a way that is truly meaningful for the patient. This brief chapter will discuss examples through the history of healing and the breakthroughs of the 16th to the 20th century in spite of suppression of new ideas. We still face the challenges of "the closed mind" among physicians, scientists, and those who direct funding, and in some cases are analogous to situations that have impeded progress in the past. Great credit should be given to the dedicated teachers and innovators in wound healing who, along with their followers, are bound to break through with solutions to clinical wound care. PMID- 17276196 TI - Pathophysiology of acute wound healing. AB - Wound healing is a complex process that can be divided into at least 3 continuous and overlapping processes: an inflammatory reaction, a proliferative process leading to tissue restoration, and, eventually, tissue remodeling. Wound healing processes are strictly regulated by multiple growth factors and cytokines released at the wound site. Although the desirable final result of coordinated healing would be the formation of tissue with a similar structure and comparable functions as with intact skin, regeneration is uncommon (with notable exceptions such as early fetal healing); healing however results in a structurally and functionally satisfactory but not identical outcome. Alterations that disrupt controlled healing processes would extend tissue damage and repair. The pathobiologic states may lead to chronic or nonhealing wounds or excessive fibrosis. PMID- 17276197 TI - Impaired wound healing. AB - Nonhealing wounds represent a significant cause of morbidity and mortality for a large portion of the population. One of the underlying mechanisms responsible for the failure of chronic wounds to heal is an out-of-control inflammatory response that is self-sustaining. Underappreciation of the inherent complexity of the healing wound has led to the failure of monotherapies, with no significant reduction in wound healing times. A model of the inflammatory profile of a nonhealing wound is one in which the equilibrium between synthesis and degradation has been shifted toward degradation. This review summarizes the current information regarding acute wound healing responses as contrasted to the delayed response characteristic of chronic wounds. In addition, some initial complexity theoretical models are proposed to define and explain the underlying pathophysiology. PMID- 17276198 TI - Abnormal wound healing: keloids. AB - Wound healing is a complex and carefully regulated physiologic response to a traumatic injury. Deregulation of this coordinated process can lead to exuberant scar formation as seen in keloids and hypertrophic scars. Despite their common occurrence, keloids remain one of the most challenging dermatologic conditions to successfully treat and may have significant psychosocial impact for the patient. In this review, we discuss the clinical features, genetics, epidemiology, and treatment of keloids. PMID- 17276199 TI - Advances in wound dressings. AB - Wound dressings have undergone an evolutionary process from natural materials that simply covered and concealed the wound, to materials that focused on moisture management, and more recently, to materials that either deliver active ingredients or interact directly with cells or specific chemicals in the local wound environment. Advances in dressings technology have led to a new proliferation of topical products that do more than just cover and conceal, but that also can facilitate the healing process as well as address specific issues in nonhealing wounds. Dressings may play an important adjunctive role in concert with overall efforts to manage the underlying causes of chronic nonhealing wounds. PMID- 17276200 TI - Clinical aspects of full-thickness wound healing. AB - Optimal management of full-thickness wounds requires a thorough knowledge of wound-healing principles and practices. In the absence of underlying disease, almost every full-thickness wound will heal with minimal intervention; however, the process can be enhanced by judicious wound management. The first clinical decision to be made is whether to repair the wound or to allow it to heal by second intention. This decision is guided by a host of objective and subjective factors. Reconstruction options include primary closure, flaps, and grafts. Materials to aid reconstruction, including the introduction of tissue adhesives, continue to evolve. Both primary and secondary intention wounds are aided by occlusive dressings and adjutants. A plethora of wound-healing adjuncts have been developed to aid wound healing in diseased states, and a working knowledge of their use is beneficial in managing all full-thickness wounds. PMID- 17276201 TI - Stress and wound healing. AB - There are substantial data to suggest that stress-induced disruption of neuroendocrine immune equilibrium is detrimental to health, with the strongest evidence to date in wound healing. Murine and human studies demonstrated that the down-regulation of the early inflammatory response by an increase in cortisol levels results in delayed wound repair and identified several potential cellular mechanisms linking stress and wound healing. The impact of stress on wound healing has been studied almost exclusively in acute experimentally induced wounds. Because chronic wounds are different entities from acute wounds, the cellular/molecular mechanisms by which stress affects acute wound healing may not necessarily be applied to chronic wounds, hence, the need for studies in stress and chronic wound (eg, diabetic foot ulcer) healing. PMID- 17276202 TI - The hormonal regulation of cutaneous wound healing. AB - Conditions of impaired wound healing in the elderly are associated with substantial morbidity and mortality and impose a significant financial burden upon the world's health services. The findings of a series of recent studies have served to highlight the contrasting contributions made by sex steroid hormones to the regulation of cutaneous repair processes. Although estrogens accelerate healing, the actions of the "male" sex hormones 5alpha-dihydrotestosterone and testosterone are primarily deleterious. The shift that occurs in the balance between serum estrogen and androgen levels as a normal feature of human aging may therefore have important consequences for fundamental tissue repair processes. PMID- 17276203 TI - A biochemical approach to wound healing through the use of modalities. AB - Wound healing is a complex pathway that is energy dependent. Nonhealing wounds frequently require the use of physical modalities to achieve healing. There is much debate over which treatment modality to use, with varying clinical results in the literature. This review paper describes a common biochemical pathway that helps the clinician understand, at a molecular level, how the transference of energy to a wound can result in positive clinical results. The mechanisms of action for ultraviolet light, electrical stimulation, and ultrasound are reviewed along with a proposed biochemical roadmap. An emphasis on protein biochemistry is supported with an extensive review of the literature. PMID- 17276204 TI - Stem cells in cutaneous wound healing. AB - Treatment of chronic wounds remains difficult, in spite of better understanding of pathophysiologic principles and greater adherence to recognized standards of care. Even with recent advances stemming from breakthroughs in recombinant growth factors and bioengineered skin, up to almost 50% of chronic wounds that have been present for more than a year remain resistant to treatment. Because of these realities, there is excitement in the use of stem cells to offset impaired healing. Early data appear encouraging, but much work remains to be done. Although pilot studies suggest that multipotent adult stem cells can accelerate wound repair or even reconstitute the wound bed, the answers will need to come from randomized clinical trials. Thus far, considerable focus has been placed on bone marrow-derived mesenchymal stem cells, and there are now promising approaches for introducing them into the wound. It might turn out, however, that other types of stem cells will be more effective, including those derived from hair follicles or, perhaps, subsets of bone marrow-derived cultured cells. Still, proper wound care and adherence to basic principles cannot be bypassed, even by the most sophisticated approaches. PMID- 17276206 TI - Peripheral arterial disease: diagnosis, treatment, and systemic implications. AB - Peripheral arterial disease is common in adults and is found in many patients with lower extremity ulcers. It is important to diagnose peripheral arterial disease not only because of its impact on the involved lower extremity but also because it often occurs with atherosclerotic disease in other vascular beds. Although patient symptoms may be helpful in the diagnosis, most afflicted patients either are asymptomatic or have atypical symptoms. Physical examination, an ankle-brachial index, referral to a noninvasive vascular laboratory, contrast angiography, and magnetic resonance angiography can be helpful diagnostically. Beneficial therapies include smoking cessation, exercise therapy, cholesterol reduction, antiplatelet therapy, and treatment of hypertension and diabetes. For patients with symptomatic claudication, cilostazol can be considered. Patients with nonhealing ulcers, rest pain, or severe claudication should be referred for interventions. PMID- 17276208 TI - The diabetic foot. AB - Diabetic foot problems are common throughout the world, resulting in major medical, social and economic consequences for the patients, their families, and society. Foot ulcers are more likely to be of neuropathic origin, and therefore eminently preventable. People at greatest risk of ulceration can easily be identified by careful clinical examination of the feet: education and frequent follow-up is indicated for these patients. When infection complicates a foot ulcer, the combination can be limb or life-threatening. Infection is defined clinically, but wound cultures assist in identifying the causative pathogens. Tissue specimens are strongly preferred to wound swabs for wound cultures. Antimicrobial therapy should be guided by culture results, and although such therapy may cure the infection, it does not heal the wound. Alleviation of the mechanical load on ulcers (offloading) should always be a part of treatment. Plantar neuropathic ulcers typically heal in 6 weeks with irremovable casting, because pressure at the ulcer site is mitigated and compliance is enforced. The success of other approaches to offloading similarly depends on the patients' adherence to the effectiveness of pressure relief. PMID- 17276207 TI - The decubitus ulcer: many questions but few definitive answers. AB - Decubitus ulcers appear to be associated with insidious trauma. Differential diagnosis can be tricky, and etiology is controversial with sustained localized pressure which plays a significant role. Sustained pressure can stretch soft tissues and blood vessels, causing multiple microthrombi around the point of maximum compression. This leads to prolonged ischemia and produces a plaque of dead tissue surrounded by microthrombi. Prevention often includes regular movement or supports that move the patient. Good nutrition is important, but the adverse effects of fever should not be overlooked. Anti-thrombotic agents should be considered. Occlusive dressings can be used for existing ulcers, while traditional treatments are less appropriate. Pressure and other stresses theoretically should be relieved. PMID- 17276209 TI - Venous ulcers. AB - Chronic venous ulceration is a common and important medical problem, which causes significant morbidity. Venous ulcers are expensive to treat, have substantial economic effects in terms of days of work lost, and adversely impact patient's quality of life. History and clinical findings are helpful in making the diagnosis of venous ulceration, but additional diagnostic testing is helpful in confirming the diagnosis and excluding arterial disease. The objectives of venous ulcer management include healing of the ulcer, prevention of recurrence, and improvement of edema. Compression is the cornerstone of venous ulcer therapy. Adjunctive modalities such as biologic skin substitutes, dressings, debridement, surgical intervention, and drugs may also facilitate the healing process. PMID- 17276205 TI - Gene therapy and wound healing. AB - Wound repair involves the sequential interaction of various cell types, extracellular matrix molecules, and soluble mediators. During the past 10 years, much new information on signals controlling wound cell behavior has emerged. This knowledge has led to a number of novel therapeutic strategies. In particular, the local delivery of pluripotent growth factor molecules to the injured tissue has been intensively investigated over the past decade. Limited success of clinical trails indicates that a crucial aspect of the growth factor wound healing strategy is the effective delivery of these polypeptides to the wound site. A molecular approach in which genetically modified cells synthesize and deliver the desired growth factor in regulated fashion has been used to overcome the limitations associated with the (topical) application of recombinant growth factor proteins. We have summarized the molecular and cellular basis of repair mechanisms and their failure, and we give an overview of techniques and studies applied to gene transfer in tissue repair. PMID- 17276210 TI - Inflammatory ulcers. AB - Skin ulcerations may develop as a manifestation of a variety of different diseases or may result from some nondisease phenomena. Inflammatory ulcers refer specifically to those ulcerations in which inflammation is the primary pathologic process resulting in lesion formation; that is, inflammation is the cause rather than the consequence of the ulcer. This review will consider several types of inflammatory ulcers that the clinician may encounter in his or her practice. PMID- 17276211 TI - Of Latin and its use in medical literature. PMID- 17276212 TI - Patients seen and lessons learned. PMID- 17276214 TI - The Libyan AIDS crisis and a miscarriage of justice. PMID- 17276215 TI - Joao Ramos-e-Silva: my grandfather (June 11, 1898-November 26, 1983). PMID- 17276216 TI - Shoulder instability: surgical versus nonsurgical treatment. PMID- 17276217 TI - Primary repair versus conservative treatment of first-time traumatic anterior dislocation of the shoulder: a randomized study with 10-year follow-up. AB - PURPOSE: The purpose of this study was to compare long-term results after surgical and conservative primary treatment of first-time traumatic anterior shoulder dislocation. METHODS: Arthroscopic diagnosis after first-time traumatic anterior shoulder dislocation was performed, and in cases of a Baker type 1, 2, or 3 lesion, patients were randomized either to conservative treatment with a fixed sling for 1 week followed by a rehabilitation program or to open repair with a similar rehabilitation program. RESULTS: In this study 76 patients (14 female and 62 male patients), aged 15 to 39 years, were randomized to surgical repair (n = 37) or conservative treatment (n = 39). Of the patients, 6.6% had Baker type 1 lesions, 13.2% had type 2 lesions, and 80.3% had type 3 lesions. After a minimum of 2 years' follow-up, 56% had recurrence after conservative treatment and 3% after open repair (P < .005). Among nondislocators, 39% in the conservative group and 7% in the repair group had a positive apprehension test. When evaluated after 10 years by use of the Oxford self-assessment score, 72% of patients in the surgical group had good or excellent results. Of the conservatively treated patients, 75% had unsatisfactory results because of recurrence, instability, and pain or stiffness. CONCLUSIONS: Arthroscopic evaluation after first-time anterior shoulder dislocation revealed a Baker type 2 or 3 lesion in 93.5% of patients. At 2 years' follow-up, 21 (54%) of the conservatively treated patients had recurrence, as compared with 1 patient with recurrence (3%) after open surgical repair. After 8 years, a further 3 patients in the conservatively treated group had redislocations, 1 had subjective instability, and 4 had pain or stiffness, resulting in 74% having unsatisfactory results according to the Oxford score. Of the patients who had surgical repair, 72% had good or excellent results after 10 years. Because open repair produces superior results compared with conservative treatment, we recommend that the surgeon consider performing primary repair in active patients to reduce the risk of recurrence. LEVEL OF EVIDENCE: Level I, high-quality prospective, randomized controlled trial. PMID- 17276218 TI - Complications after arthroscopic rotator cuff repair. AB - PURPOSE: The purpose of this study was to determine the complication rate of a consecutive series of patients undergoing arthroscopic rotator cuff repair. METHODS: From January 2003 to June 2003, all patients undergoing primary arthroscopic rotator cuff repair were identified. A total of 263 patients were identified. Medical records were reviewed to identify complications in the study patients. RESULTS: A total of 28 patients (10.6%) sustained a complication. Complications included shoulder stiffness, failure of healing, infection, reflex sympathetic dystrophy, deep venous thrombosis, and death. CONCLUSIONS: The most common complication was recognized as persistent stiffness that usually responded to extensive physical therapy. Complications after arthroscopic rotator cuff repair are similar to results published for open rotator cuff repair. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17276219 TI - An evaluation of shoulder external rotation braces. AB - PURPOSE: The purpose of the present study was to evaluate 4 commercially available shoulder external rotation braces to determine their ability to achieve and maintain shoulder external rotation. In addition, for each brace, we collected patient-derived data on comfort level, ease of application, and ease of performing activities of daily living during brace wear. METHODS: Four commercially available shoulder external rotation braces were evaluated for their ability to achieve and maintain external rotation in 12 healthy subjects. RESULTS: Significant differences were noted between braces in their ability to achieve and maintain shoulder external rotation, as well as in their comfort ratings. CONCLUSIONS: We have shown that the commercially available shoulder external rotation braces evaluated in this study vary in (1) ability to achieve and maintain a desired position of external rotation of the shoulder, and (2) comfort ratings. CLINICAL RELEVANCE: Selection of an external rotation brace should involve consideration of the device's performance and comfort profile. PMID- 17276220 TI - Biomechanical comparison of 3 suture anchor configurations for repair of type II SLAP lesions. AB - PURPOSE: Our purpose was to compare 3 commonly used suture anchor configurations for repair of type II SLAP lesions. METHODS: Biomechanical testing was performed on 3 groups of 7 cadaveric shoulders by use of an optical linear strain measurement system. Standardized type II SLAP lesions were created and repaired via 3 suture anchor configurations: (1) a single simple suture anterior to the biceps; (2) two simple sutures, one anterior and one posterior to the biceps; and (3) a single mattress suture through the biceps anchor. Cyclic traction was applied to the biceps tendon, and strain failure (defined as 2 mm of permanent displacement), yield, and pullout loads were measured. RESULTS: The mean load to strain failure was 63 N in group 1, 70 N in group 2, and 106 N in group 3. The mean load to ultimate failure was 140 N in group 1, 194 N in group 2, and 194 N in group 3. Strain failure load was significantly higher in the mattress suture group than in either of the other two groups (P < .05). Groups 2 and 3 both had a significantly higher load to ultimate failure than group 1. CONCLUSIONS: When type II SLAP lesions were subjected to cyclic traction, the load to strain failure was greater with a single anchor and mattress suture than with one or two anchors with simple sutures around the labrum. Fixation with two simple sutures appears to provide intermediate load to strain failure. CLINICAL RELEVANCE: The results of this study suggest that a single anchor with a mattress suture may be a biomechanically advantageous construct for the repair of type II SLAP lesions. PMID- 17276221 TI - A biomechanical comparison of 2 ulnar collateral ligament reconstruction techniques. AB - PURPOSE: To biomechanically compare the Jobe transosseous ulnar collateral ligament (UCL) reconstruction procedure and an interference screw reconstruction (ISR) technique versus the intact elbow UCL. METHODS: Intact stiffness of 10 matched cadaveric elbow pairs was tested via submaximal valgus loading at 4 flexion angles. From each pair, a metal ISR and a traditional transosseous Jobe reconstruction was performed with the use of matched hamstring tendon grafts. Initial stiffness (graft tension), overall stiffness, strain, and failure strength of reconstructed elbows were then tested. RESULTS: At each tested flexion angle, Jobe constructs reproduced the initial and overall stiffness of the intact ligament. ISR constructs did not reproduce the overall stiffness of the native ligament at any flexion angle, and they reproduced the initial stiffness only at 30 degrees and 120 degrees of flexion. Jobe constructs were significantly stronger, failing (10 degrees of displacement) at 22.7 Nm after absorbing 1.58 Nm of energy, versus 13.4 Nm and 0.97 Nm for ISR constructs. In all, 40% of bone tunnel reconstructions failed via tunnel fracture, and 70% of interference screw constructs failed via graft slippage. CONCLUSIONS: The failure strength and initial and overall stiffness of a traditional Jobe bone tunnel UCL reconstruction are superior to those of an ISR, and only traditional Jobe bone tunnel reconstruction reproduces the initial and overall stiffness of an intact UCL. CLINICAL RELEVANCE: Many UCL reconstruction techniques have been described, and a paucity of biomechanical data supports their use. This study found the Jobe bone tunnel technique to be biomechanically superior to the ISR technique. PMID- 17276222 TI - Arthroscopic debridement without radial head excision of the osteoarthritic elbow. AB - PURPOSE: This study evaluated the short-term clinical outcomes of patients with osteoarthritis of the elbow joint, including grade III or IV radiocapitellar arthritis, treated with debridement of the radial head in conjunction with arthroscopic ulnohumeral arthroplasty. METHODS: Between 1993 and 1999, in 24 patients (25 elbows) who underwent arthroscopic treatment for degenerative arthritis with impingement, arthroscopic findings revealed grade III or IV radiocapitellar arthritis. All were treated by debridement of the anterior and posterior osteophytes and capsular release alone, while the radial head was left intact. Average patient age was 51 years (range, 16 to 59). Average follow-up was 67 months (range, 24 to 123). Patients were evaluated preoperatively and postoperatively with the subjective/objective scoring system of Andrews and Carson. RESULTS: Of 25 elbows treated, 24 were "better" or "much better" after surgery; 1 patient's condition was unchanged. In all, 21 patients reported minimal or no pain in the elbow, and 4 reported mild to moderate persistent pain. The average flexion-extension arc improved by 21 degrees , and the number of patients with a flexion contracture greater than 5 degrees dropped from 22 to 3 post surgery. According to the elbow rating system of Andrews and Carson, 14 patients had an excellent result, 7 good, 3 fair, and 1 poor. Twelve patients reported no limitations in their daily activities, and 12 experienced occasional problems. No surgical complications were reported. CONCLUSIONS: Arthroscopic debridement of the arthritic elbow provides reasonable pain relief and improves motion even in the presence of moderate to severe radiocapitellar chondral loss. Resecting the arthritic radial head is not essential to obtaining an excellent functional outcome. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17276223 TI - Arthroscopic treatment of symptomatic discoid meniscus in children: classification, technique, and results. AB - PURPOSE: The purpose of this study was to review the operative results of children and young adults treated arthroscopically for symptomatic discoid lateral menisci. METHODS: The medical records and radiographic studies of 27 consecutive patients (30 knees) who underwent arthroscopic treatment for symptomatic discoid meniscus between 1998 and 2002 were reviewed. RESULTS: The mean patient age was 10.1 years (range, 3 to 20 years), with 19 female and 8 male patients. The mean duration of symptoms before surgery was 13.9 months, with 28 knees (93%) having pain and 20 knees (67%) having mechanical symptoms. All patients were treated arthroscopically. Arthroscopic saucerization was successful in 28 of 30 knees. In 2 cases with large complex tears meniscal salvage was not possible and a complete arthroscopic meniscectomy was performed. Operative classification of the menisci revealed 22 complete (4 Wrisberg type) and 8 incomplete discoid menisci, with meniscal tears being present in 23 of 30 (77%). Meniscal instability was noted in 77% of knees (23 of 30), with anterior horn instability in 53% (n = 16), posterior instability in 16% (n = 5), and combined anterior and posterior instability in 6% (n = 2). All cases of anterior horn instability were treated with an outside-in arthroscopic repair technique, whereas all cases of posterior horn instability were treated with meniscal repair via an inside-out arthroscopic technique. Twenty-one patients (23 knees) had full follow-up of greater than 1 year. For these 21 patients, the mean length of follow-up was 37.4 months (range, 12 to 77 months), and at final follow-up, all patients exhibited full knee flexion beyond 135 degrees. Three patients reported residual knee pain, and four reported intermittent mechanical symptoms. At final follow-up, 2 patients felt that their activity level remained partially limited. CONCLUSIONS: Our results show the short-term efficacy of arthroscopic saucerization and repair to the capsule in selected cases of symptomatic discoid menisci. On the basis of this experience and other recent reports documenting a high rate of anterior horn instability, an arthroscopic classification system for discoid lateral menisci is proposed. Menisci are classified as complete or incomplete discoid and are then subclassified based on the presence of instability as a result of deficient capsular attachment and, finally, based on the location of the absent capsular attachment. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17276224 TI - Management of posterior cruciate ligament reconstruction after previous isolated anterior cruciate ligament reconstruction. AB - PURPOSE: The aim of our study was to analyze 20 patients who underwent secondary posterior cruciate ligament (PCL) reconstruction after previous isolated anterior cruciate ligament (ACL) reconstruction had been performed. Our analysis sought to assess ACL graft preservation or failure in these patients. A secondary aim of our study was to identify a testing protocol to be used before any surgery that would help diagnose PCL deficiency and avoid unneeded ACL reconstruction. METHODS: A total of 180 PCL reconstructions were prospectively documented, and 20 patients (11%) were identified who underwent previous isolated ACL reconstruction. Cases were analyzed to determine the quantity of ACL graft failures that had occurred and the need for ACL graft removal due to a fixed posterior subluxation. Patient charts were thoroughly reviewed, so investigators could identify the number of patients with incorrect diagnosis (PCL involvement was overlooked or an intact ACL was replaced) and the number with incorrect management (isolated ACL reconstruction was performed even though PCL involvement was recognized). RESULTS: A fixed posterior subluxation was present in 4 cases; this necessitated subsequent ACL graft resection in 2 patients to release subluxation prior to PCL reconstruction. In all, 7 ACL grafts failed because of overlooked posterolateral instability. In only 11 of 20 cases, the initial ACL graft could be preserved. ACL reconstruction was performed because of incorrect diagnosis in 16 patients and incorrect management in 4. CONCLUSIONS: A considerably high number of overlooked or underestimated PCL injuries led to isolated ACL reconstruction, which indicates that diagnostic difficulties still occur among orthopaedic surgeons who are not highly specialized. Beside persistent posterior laxity, a failed ACL graft was the main reason for a second operation, which required bicruciate ligament reconstruction. To avoid incorrect management and incorrect diagnosis, leading to isolated ACL reconstruction in PCL deficiency, we recommend that stress radiography be performed to detect eventual posterior instability. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17276225 TI - Patellofemoral evaluation with radiographs and computed tomography scans in 60 knees of asymptomatic subjects. AB - PURPOSE: The objectives of this study were to show the results of patellofemoral joint imaging in healthy volunteers, to propose a standardization of the technique, and to test the statistical correlation and reliability of the different imaging results. METHODS: In 30 healthy police academy student volunteers of both sexes, standard knee radiographs and computed tomography (CT) scans were obtained. The angles and distances were measured, and a statistical analysis was applied. The results are presented as mean +/- 2 SDs throughout. RESULTS: The mean Laurin lateral patellofemoral angle on radiographs was 16.4 degrees +/- 8.7 degrees. The mean Insall-Salvati and Caton-Deschamps indexes were 1.09 +/- 0.24 and 0.95 +/- 0.29, respectively. The CT scan values for tilt were determined for the lateral patellofemoral angle by use of both facets (-8.1 degrees +/- 9.8 degrees), the Laurin lateral patellofemoral angle (8.1 degrees +/ 14.5 degrees), the condyle-patellar angle with the lateral facet (14.5 degrees +/- 14 degrees), and the patella major axis (-11.1 degrees +/- 10.6 degrees). The sulcus angle, congruence angle (Merchant angle), and condyle-lateral angle were also obtained on CT scans, with mean values of 139.7 degrees +/- 20.4 degrees , 5.15 degrees +/- 32.6 degrees , and 22.1 degrees +/- 9 degrees , respectively. The tibiofemoral rotation was assessed with the indexes for the distance between the trochlear groove and anterior tibial tuberosity and the distance between the posterior femoral dome and anterior tibial tuberosity. The values for these two indexes were 13.6 +/- 8.8 mm and 17.8 +/- 9.2 mm, respectively. Some parameters showed sex differences. CONCLUSIONS: There are good statistical correlations between some of the tilt values on the radiographs and CT scans, indicating that they move together. The values on the CT scans show good reliability. The CT scans and radiographs are good tests by which to evaluate and quantify patellar alignment. LEVEL OF EVIDENCE: Level I, testing of previously developed diagnostic criteria. PMID- 17276226 TI - Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. AB - PURPOSE: The purpose of this study was to evaluate the repaired tissues formed in full-thickness cartilage defects in a rabbit model implanted with 4 types of chondrogenic cells, including chondrocytes, mesenchymal stem cells (MSCs) and fibroblasts from rabbit, and human umbilical cord blood (hUCB) stem cells. METHODS: Chondrocytes, MSCs, and fibroblasts were isolated from 6-week-old New Zealand rabbits; hUCB stem cells were isolated from the umbilical cord blood of newborn children. These 4 types of cells were cultured in vitro and embedded in polylactic acid (PLA) matrices. Full-thickness defects were produced in the femoral trochlear grooves of both knees in 36 adult New Zealand White rabbits. Cell/PLA composites were transplanted into cartilage defects. A total of 5 groups were formed according to implanted cell type: Group A, chondrocytes; Group B, MSCs; Group C, fibroblasts; Group D, hUCB stem cells; and Group E, no cells (control group). Repaired tissues were evaluated grossly, histologically, and immunohistochemically at 6 weeks and 12 weeks after implantation. RESULTS: In Groups A and B, defects were repaired with hyaline-like cartilage. In Group C, defects were repaired with fibrous tissue. In Group D, defects were repaired primarily with fibrous tissue and scattered chondrocytes; in some specimens, defects were repaired with a thin layer of hyaline-like cartilage at 12 weeks. In Group E, defects were repaired with fibrous tissue. Histologic scores in Groups A and B were significantly higher than those in Groups C, D, and E at 6 and 12 weeks after transplantation. CONCLUSIONS: Full-thickness cartilage defects treated with chondrocyte or MSC transplantation were repaired with hyaline-like cartilage tissue, and repair was significantly better than in tissues treated with fibroblasts and hUCB stem cells, as well as in the control group. Repaired tissues treated with MSCs appeared to have better cell arrangement, subchondral bone remodeling, and integration with surrounding cartilage than did repaired tissues generated by chondrocyte implantation. MSCs might be the most suitable cell source for cartilage repair. Further investigation into hUCB stem cell transplantation is needed. CLINICAL RELEVANCE: In our study of rabbits, MSCs supplied the most promising cell source for cartilage repair. PMID- 17276227 TI - Histologic evaluation of osteochondral loose bodies and repaired tissues after fixation. AB - PURPOSE: The purpose of this study was to evaluate histologic changes in osteochondral loose bodies in the rabbit knee joint and histologic changes in repaired tissue after fixation of osteochondral loose bodies following isolation periods of varying length. METHODS: We harvested osteochondral fragments from the patellar groove in rabbit knee joints and left them in the lateral gutters of the joints for periods of varying duration to create osteochondral loose bodies. We then evaluated histologic and immunohistochemical changes within these loose bodies. Next, we fixed osteochondral loose bodies that had been isolated for various periods within the joints to the osteochondral defect in the patellar groove. Twelve weeks after fixation, repaired tissues were evaluated histologically and immunohistochemically, and results were analyzed according to the varying isolation periods of fragments. RESULTS: Extracellular matrix and type II collagen expression of osteochondral loose bodies deteriorated with increased duration of fragment isolation periods. A significantly negative correlation was noted between length of isolation periods and histologic grading scores. After osteochondral loose bodies had been fixed, repaired tissues deteriorated significantly in accordance with duration of fragment isolation periods. However, in some cases, even when osteochondral fragments had been isolated for 12 weeks, repaired tissues showed dense extracellular matrix stained by safranin O and abundant type II collagen expression, which indicated regeneration of the cartilage layer. CONCLUSIONS: Osteochondral loose bodies and repaired tissues deteriorated after they were fixed to osteochondral defects. Although a direct correlation was noted between isolation periods of fragments and time to their deterioration, some osteochondral loose bodies showed regeneration of cartilage after fixation. CLINICAL RELEVANCE: Clinically, reduction of osteochondral loose bodies should be performed as early as possible, if these can be found. However, even if the fragment seems to be old, fragment fixation is worthy of consideration. PMID- 17276228 TI - Effects of low-intensity pulsed ultrasound on tendon-bone healing in an intra articular sheep knee model. AB - PURPOSE: This study reports the mechanical and histologic properties of intra articular tendon-bone healing with the application of low-intensity pulsed ultrasound (LIPUS) in an ovine knee model. METHODS: A single digital extensor tendon autograft from the right hoof was used as the graft in 89 adult sheep. Femoral fixation was achieved with an EndoButton (Smith & Nephew Endoscopy, Andover, MA) and tibial fixation by tying over a bony post. LIPUS treatment was performed daily for 20 minutes over the femoral and tibial tunnels until sacrifice in all groups, apart from the 26-week group, which was treated only for the first 12 weeks. Histology was performed at 3, 6, 12, and 26 weeks. Mechanical testing was performed at 6, 12, and 26 weeks. RESULTS: The LIPUS-treated group showed increased cellular activity at the tendon-bone interface and general improvement in tendon-bone integration and vascularity. Stiffness and peak load were greater compared with the control group at 26 weeks after surgery (P < .05). CONCLUSIONS: The application of LIPUS appears to improve healing at the tendon bone interface for soft tissue grafts fixed with a suspensory fixation technique. Histology supports a benefit based on increased integration between tendon and bone and a biologically more active interface, which would account for the improved mechanical properties. CLINICAL RELEVANCE: The indications of LIPUS may be expanded to include tendon-bone healing, for example, in anterior cruciate ligament reconstruction. PMID- 17276229 TI - Bone morphogenetic proteins and Smad expression in ovine tendon-bone healing. AB - PURPOSE: Bone morphogenetic proteins (BMPs) are being developed to improve tendon bone healing. To do this, it is essential to understand the endogenous expression of BMPs and their downstream signal transduction factors, Smads, during tendon bone healing. METHODS: An extra-articular patellar tendon-bone healing ovine model was set up, and histologic evaluation of the healing progress at the tendon bone interface at 1, 2, 3, and 6 weeks was performed. Immunohistochemical staining of BMP-2, BMP-7, Smad1, Smad4, and Smad5 was carried out in all sections. RESULTS: The model revealed formation of a loose granuloma tissue layer between the tendon and bone at 1 week, remodeling starting at 2 weeks, and Sharpey-like collagen fiber formation at 3 and 6 weeks. All detected factors were elevated at the tendon-bone interface during healing, and the expression peaked at 2 to 3 weeks. The cells involved were osteoblastic-like cells, osteoclastic like cells, mesenchymal cells, and fibroblasts. BMP-7 staining was mainly at the interface close to the bony side, whereas BMP-2 expression shifted to the tendon side at 6 weeks. The expression pattern of Smad1 and Smad5 was similar to that of BMP-7. Smad1 was also found to be expressed in osteoclastic-like cells at 1 and 2 weeks. Smad4 expression was the highest among all of the factors at all time points. CONCLUSIONS: The data suggest that endogenous BMP-2 and BMP-7 participate in tendon-bone healing and their functions involve their downstream signal transduction mediators, Smad1, Smad4, and Smad5. CLINICAL RELEVANCE: The temporal expression of BMPs should be considered when setting up therapeutic strategies using BMPs. PMID- 17276230 TI - Minor shoulder instability. AB - The wide spectrum of shoulder instability is difficult to include in 1 classification. The distinction between traumatic, unidirectional, and atraumatic multidirectional instability is still widely used, even though this classification is not sufficiently precise to include all the different pathological findings of shoulder instability. We present "minor instability," which is a pathological condition causing a dysfunction of the glenohumeral articulation, especially in combination with microtrauma, repetitive or not, or after a period of immobilization or inactivity. When "minor shoulder instability" is suspected, the patient's history and detailed clinical examination represent the most important factors when establishing the diagnosis. In particular, the apprehension test stressing the middle glenohumeral ligament (MGHL)/labral complex in the position of midabduction and external rotation may be painful and may even reveal anterior instability or subluxation. Conventional radiographs are negative in most cases, as is magnetic resonance imaging arthrography. It is only after an accurate arthroscopic assessment that the pathological lesion can be found. The major pathological process can be identified at the level of the anterior superior labrum, in particular the MGHL complex, and appears as hyperemia, fraying, stretching, loosening, thinning, hypoplasia, or even absence. It may, however, be difficult to distinguish between a normal variant and a pathological lesion. Clinical symptoms and examination should always be correlated with arthroscopic findings. Recommended treatment is to restore shoulder stability and thereby prevent shoulder pain secondary to the increase in laxity. A reduction in range of motion should be expected during the postoperative phase, at least up to six to nine months. External rotation is usually permanently reduced by a few degrees. PMID- 17276231 TI - Arthroscopic suprascapular nerve release at the suprascapular notch in a cadaveric model: an anatomic approach. AB - Arthroscopic release of the suprascapular nerve at the suprascapular notch, to our knowledge, has rarely been described. The purpose of this study was to evaluate the feasibility and relevant anatomic landmarks in a cadaveric model that can be identified arthroscopically for reliable and reproducible arthroscopic release of the superior transverse scapular (STS) ligament. In 8 fresh-frozen cadaveric shoulders, arthroscopic release of the STS ligament was performed. The acromioclavicular joint is first identified while viewing through a posterior subacromial portal. The distal clavicle is then followed medially until the most lateral portion of the coracoclavicular (CC) ligaments (trapezoid ligament) is identified. The most medial margin of the CC ligaments (conoid ligament) is identified, and the trapezoid and conoid ligaments are dissected and identified individually. The conoid ligament is followed inferiorly and medially to the base of the coracoid. At the base of the coracoid, the confluence of the trapezoid and conoid ligaments (CC) and the STS ligament is identified. The STS ligament can be identified coursing horizontally across the field of view. The STS ligament may be incised by use of dissecting scissors through a lateral, accessory lateral, or accessory posterior portal, releasing the suprascapular nerve. PMID- 17276232 TI - Posterior instability of the shoulder following thermal capsulorrhaphy for multidirectional instability. AB - Patients with multidirectional instability (MDI) of the shoulder can be treated with arthroscopic thermal capsulorrhaphy. However, recent literature suggests that complications and failures associated with this technique are on the rise. We present the case of a 30-year-old female patient who was treated for a failed thermal capsulorrhaphy. She had undergone this treatment of her left shoulder for MDI but had persistent pain with overhead activities and clicking in the posterior shoulder. Her history and physical examination were consistent with persistent posterior unidirectional instability of the shoulder. Magnetic resonance imaging showed a possible separation of the capsule from the posterior glenoid. After conservative management had been attempted several times, an arthroscopic repair was performed. At surgery, the anterior and inferior capsule appeared to be tight. However, the posterior capsule was extremely lax and patulous, but intact. A posterior capsule plication was performed arthroscopically, along with a rotator interval closure. Postoperatively, the patient was maintained in a sling that kept the arm in neutral rotation. At 6 weeks, the sling was removed, and a slow, progressive program of therapy was initiated. Stress on the posterior capsule was not permitted for 3 months. At 1 year follow-up, the patient had full pain-free range of motion and returned to participation in sports without limitation. PMID- 17276233 TI - Arthroscopic retrieval of a broken guidewire fragment from the hip joint after cannulated screw fixation of slipped capital femoral epiphysis. AB - The use of cannulated screws for internal fixation of slipped capital femoral epiphysis (SCFE) is recognized as the standard method of treatment and has fewer complications compared with previous methods such as pins or tri-flanged nails. Some complications related to guidewires have been reported in the treatment SCFE. The most dangerous complication is inadvertent advance of the guidewire into the pelvic cavity. Guidewire breakage is frequent and maybe under-reported. Articular migration of a guidewire fragment has potentially devastating effects and implies a second surgical procedure. Open arthrotomy is the traditional method for fragment removal from the hip joint. We report the case of a 12-year old-girl with bilateral SCFE. Both hips were fixed with cannulated screws. A guidewire broke inside her right hip, leaving an articular fragment located at the inferior-posterior acetabular notch. Hip arthroscopy was performed 6 weeks after the index procedure; the fragment was located and removed from the joint. No evidence of cartilage damage other than the perforation created by the guidewire was found. Hip arthroscopy is an attractive option for articular foreign body removal; it has the potential for less morbidity and is adequate for evaluating and treating articular cartilage lesions. PMID- 17276234 TI - A new symptomatic intra-articular cord-like structure associated with discoid meniscus. AB - We introduce a new, not yet described cord-like structure of the knee of children associated with discoid or enlarged menisci. This structure was responsible for knee pathology (loss of extension) in 3 cases. The patients (5 to 8 years of age) complained of knee pain without skeletal abnormality or trauma. Magnetic resonance imaging revealed enlarged or discoid lateral menisci. The patients showed increasing limp with limited range of motion. Lack of extension was between 10 degrees and 45 degrees and continued under anesthesia. During arthroscopy, the menisci and the anterior and posterior cruciate ligaments (ACL, PCL) showed no abnormality other than the variant of the lateral meniscus described above. A tight cord-like structure was imposed, running laterally along the ACL. This cord-like structure was attached to the lateral femoral intercondylar area and the posterior horn region of the lateral meniscus in a sail-like shape. Two knees showed abnormal mobility of the lateral meniscus, tending to luxate. The ligamentous structure was cut stepwise lateral to the ACL, leaving the entire lateral meniscus undisturbed. Finally, full extension was achieved. Examination 7 to 27 months after surgery showed asymptomatic knees. This ligamentous structure is an important differential diagnosis to symptoms usually referred to as meniscus pathology. The appropriate treatment involves dissection. A loss of meniscal tissue followed by development of osteoarthritis can be prevented. PMID- 17276236 TI - Appropriate informed consent, then randomization is the only ethical way! PMID- 17276237 TI - Quality will always distinguish itself. PMID- 17276240 TI - Excimer laser refractive surgery in patients with underlying autoimmune diseases. PMID- 17276241 TI - Spontaneous IOL-CTR dislocation. PMID- 17276244 TI - Phacotrabeculectomy study. PMID- 17276245 TI - Iris hook as a management technique for lens-iris diaphragm retropulsion syndrome. PMID- 17276247 TI - Lens-iris diaphragm retropulsion syndrome and iridotomies. PMID- 17276248 TI - Consultation section. Cataract surgical problem. PMID- 17276255 TI - Descemet's stripping endothelial keratoplasty under topical anesthesia. AB - We describe a technique for performing Descemet's stripping endothelial keratoplasty under topical anesthesia and report the results in 7 patients. No patient reported intraoperative discomfort, and no operative complications were noted. Using a topical anesthetic approach in appropriate patients eliminates the risks associated with retrobulbar and peribulbar blocks. PMID- 17276256 TI - Simple technique to unfold the donor corneal lenticule during Descemet's stripping and automated endothelial keratoplasty. AB - We describe a technique to facilitate unfolding and prevent inversion of the donor corneal lenticule during Descemet's stripping and automated endothelial keratoplasty (DSAEK). The donor corneal lenticule is unfolded in the anterior chamber using a bent 30-gauge needle on a 3 cc air syringe. The needle tip is used to pinion the edge of the lenticule while an air bubble is simultaneously injected between the folded edges of the donor graft. A gentian-violet dye mark placed on the peripheral stromal surface of the donor lenticule is used to confirm proper graft orientation. The simple technique of simultaneously fixating the donor lenticule while injecting air ensures that the graft unfolds correctly and minimizes potential mechanical trauma to the endothelium. PMID- 17276257 TI - Eleven-year follow-up of laser in situ keratomileusis. AB - PURPOSE: To report the long-term (11-year) outcomes (stability and complications) of laser in situ keratomileusis (LASIK) in patients with high myopia. SETTING: University refractive surgery center. METHODS: Seven patients (4 with bilateral treatment and 3 with unilateral treatment) who had myopic LASIK and completed 11 years of follow-up were included in the study. RESULTS: The mean age of the 2 men and 5 women was 41.7 years +/- 6.5 (SD) (range 34 to 50 years). The mean follow up was 140.18 +/- 6.70 months (range 132 to 150 months). At 11 years, the spherical equivalent error was statistically significantly reduced, from a mean of -12.96 +/- 3.17 diopters (D) (range -19.00 to -10.00 D) before LASIK to a mean of -1.14 +/- 1.67 D (range -4.25 to 1.00 D) after (P<.001). Predictability of postoperative refraction 6 months and 11 years after LASIK showed that 6 eyes (55%) were within +/-1.00 D of intended correction. No late postoperative complications occurred. Five patients (8 eyes, 73%) were satisfied with the final outcome. CONCLUSIONS: Laser in situ keratomileusis was moderately predictable in the correction of high degrees of myopia. After the sixth postoperative month, refractive and topographic stability were obtained. No long-term sight threatening complications occurred during the follow-up period. PMID- 17276258 TI - Quality of vision with the Acri. Twin asymmetric diffractive bifocal intraocular lens system. AB - PURPOSE: To assess the quality of vision in patients who had implantation of asymmetric Acri. Twin bifocal diffractive intraocular lenses (IOLs) by evaluating distance and near visual acuities and photopic and mesopic contrast sensitivity under monocular and binocular conditions. SETTING: Fernandez-Vega Ophthalmological Institute, Oviedo, Spain. METHODS: The study comprised 343 consecutive patients who had bilateral implantation of the Acri. Twin system: a distance-weighted 737D IOL and a near-weighted 733D IOL. Monocular and binocular best corrected distance visual acuities, best distance corrected near visual acuity, and distance contrast sensitivity under photopic (85 cd/m(2)) and mesopic (5 cd/m(2)) conditions were determined. RESULTS: Eyes with the 737D IOL had better best corrected distance acuity than eyes with the 733D IOL (mean 0.036 +/- 0.061 logMAR versus 0.141 +/- 0.131 logMAR) (P<.0001). Eyes with the 733D IOL had better best distance corrected near acuity than eyes with the 737D IOL (mean 0.015 +/- 0.115 logMAR versus 0.059 +/- 0.091 logMAR) (P = .0027). Binocularly, the Acri. Twin system allowed good distance and near vision; the means were 0.031 +/- 0.059 logMAR and 0.005 +/- 0.024 logMAR, respectively. Contrast sensitivity with the Acri. Twin system was within normal limits under photopic and mesopic conditions. Contrast sensitivity was statistically significantly better with the Acri. Twin system, followed by the 737D IOL and the 733D IOL under both illumination levels. CONCLUSIONS: Asymmetric bilateral implantation of the Acri. Twin IOL gave good simultaneous distance and near vision with improved contrast sensitivity under photopic and mesopic conditions. Differences between monocular and binocular visual acuity and contrast sensitivity were obtained because of the distance-/near-weighted light distribution of Acri. Twin IOLs. PMID- 17276259 TI - Spherical aberration and coma with an aspherical and a spherical intraocular lens in normal age-matched eyes. AB - PURPOSE: To study optical aberrations in eyes having uneventful cataract surgery and in-the-bag implantation of an aspherical Tecnis Z9000 intraocular lens (IOL) (AMO) or a spherical CeeOn Edge 911 IOL (Pharmacia) and compare the results with those in a group of phakic age-matched eyes. SETTING: Ophthalmic Unit, Hospital and University of Verona, Verona, Italy. MATERIALS: Three groups, each with 30 patients (30 eyes), were examined with the Topcon KR-9000PW topographer/aberrometer. Spherical aberration and coma were analyzed in detail for 4.0 mm optical zone. Internal values were obtained by subtracting corneal aberrations from ocular aberrations. Point spread function and modulation transfer function (MTF) were considered for optical quality. RESULTS: The mean internal spherical aberration Z(4)(0) was -0.048 microm +/- 0.017 (SD) in the Tecnis group, +0.033 +/- 0.026 microm in the 911 Edge group (P<.001), and -0.013 +/- 0.056 microm in the phakic group (P = .149). The mean internal vertical coma Z(3)(-1) was 0.087 +/- 0.056 microm, 0.054 +/- 0.043 microm (P = .005), and 0.044 +/- 0.044 microm (P<.001), respectively. The internal horizontal coma Z(3)(+1) showed a similar pattern; however, total resulting coma was similar in the 3 groups. The mean Strehl ratio was 0.284 +/- 0.166 in the Tecnis group, 0.145 +/- 0.077 in the 911 Edge group (P<.01), and 0.164 +/- 0.097 in the phakic group (P<.01). The MTF curve was better in the Tecnis group (P<.001). CONCLUSIONS: After uneventful implantation, the aspherical IOL yielded better ocular aberration and optical quality results than the spherical IOL. Induced coma was somewhat higher in the Tecnis group; however, the overall results were not affected. Physiologic IOL decentration after correct in-the-bag implantation did not negate the advantages of asphericity. PMID- 17276260 TI - Quality of vision after cataract surgery after Tecnis Z9000 intraocular lens implantation: effect of contrast sensitivity and wavefront aberration improvements on the quality of daily vision. AB - PURPOSE: To compare ocular performance and quality of vision in pseudophakic eyes with an aspherical intraocular lens (IOL) or a conventional spherical IOL. SETTING: Bretonneau University Hospital, Tours, France. METHODS: Twenty patients (40 eyes) were randomly divided in 2 equal groups to bilaterally receive the aspherical Tecnis Z9000 IOL (AMO) or the spherical CeeOn Edge 911 IOL (AMO). Contrast sensitivity was measured and ocular wavefront analysis performed before surgery and 6 months after. Patients completed the Activities of Daily Vision Scale (ADVS) to evaluate patient-centered visual outcomes. Other examinations included refraction before and after mydriasis and pupil diameter. RESULTS: The mean postoperative best corrected visual acuity (logMAR) was 0.03 +/- 0.05 (SD) in the Tecnis group and 0.01 +/- 0.05 in the CeeOn Edge group (P = .41). Refractive evaluation with mydriasis showed a mean myopic shift as low as -0.02 +/- 0.36 diopter (D) in the Tecnis group and -0.51 +/- 0.37 D in the CeeOn Edge group (P = .001). Mesopic contrast sensitivity at high spatial frequencies was significantly better in the Tecnis group (P<.001), while contrast sensitivity under photopic and glare conditions was not different between the 2 groups. Spherical aberration was significantly lower in the Tecnis group, which had a mean Z(4)(0) of 0.01 +/- 0.06 microm, than in the CeeOn Edge group, which had a mean Z(4)(0) of 0.16 +/- 0.12 microm (P<.001). The global score on the ADVS was not statistically different between groups; however, quality of distance vision was better in the Tecnis group than in the CeeOn Edge group (mean 99.0 +/- 2.0 versus 89.2 +/- 3.4) (P<.001). CONCLUSION: Implantation of an aspherical IOL with a negative spherical aberration resulted in reduced ocular spherical aberration and improved mesopic contrast sensitivity and led to better subjective quality of vision. PMID- 17276261 TI - Change in corneal aberrations after cataract surgery with 2 types of aspherical intraocular lenses. AB - PURPOSE: To study the effect of cataract surgery through 3.2 mm superior incisions on corneal aberrations with 2 types of monofocal intraocular lenses (IOLs) with an aspherical design. SETTING: Instituto de Optica, Consejo Superior de Investigaciones Cientificas, and Fundacion Jimenez Diaz, Madrid, Spain. METHODS: Corneal topography of 43 eyes was obtained before and after small corneal incision cataract surgery. Twenty-two eyes had implantation of a Tecnis Z9000 silicone IOL (Advanced Medical Optics) and 21 had implantation of an AcrySof IQ SN60WF acrylic IOL (Alcon Research Labs) using the recommended injector for each IOL type. The intended incision size (3.2 mm) was similar in the 2 groups. Corneal aberrations were estimated using custom-developed algorithms (based on ray tracing) for 10.0 mm and 5.0 mm pupils. Comparisons between preoperative and postoperative measurements and across the groups were made for individual Zernike terms and root-mean-square (RMS) wavefront error. RESULTS: The RMS (excluding tilt and defocus) did not change in the AcrySof IQ group and increased significantly in the Tecnis group with the 10.0 mm and 5.0 mm pupil diameters. Spherical aberration and coma-like terms did not change significantly; however, vertical astigmatism, vertical trefoil, and vertical tetrafoil changed significantly with surgery with the 10.0 mm and 5.0 mm pupil diameters (P<.0005). The induced wave aberration pattern for 3rd- and higher order aberrations consistently showed a superior lobe, resulting from a combination of positive vertical trefoil (Z(3)(-3)) and negative tetrafoil (Z(4)(4)). The mean vertical astigmatism increased by 2.47 microm +/- 1.49 (SD) and 1.74 +/- 1.44 microm, vertical trefoil increased by 1.81 +/- 1.19 microm and 1.20 +/- 1.34 microm, and tetrafoil increased by -1.10 +/- 0.78 microm and -0.89 +/- 0.68 microm in the Tecnis group and AcrySof IQ group, respectively. There were no significant differences between the corneal aberrations in the 2 postoperative groups, although there was a tendency toward more terms or orders changing statistically significantly in the Tecnis group, which had slightly higher amounts of induced aberrations. CONCLUSIONS: Cataract surgery with a small superior incision induced consistent and significant changes in several corneal Zernike terms (vertical astigmatism, trefoil, and tetrafoil), resulting in a significantly increased overall corneal RMS wavefront error. These results can be used to improve predictions of optical performance with new IOL designs using computer eye models and identify the potentially different impact of incision strategies on cataract surgery. PMID- 17276263 TI - Critical flicker fusion test of potential vision. AB - PURPOSE: To continue developing a potential vision test based on the critical flicker fusion (CFF) phenomenon by using a brighter stimulus and optimizing its size. SETTING: Flinders Eye Centre, Flinders Medical Centre, Flinders University, Bedford Park, South Australia, Australia. METHODS: In a prospective nonrandomized study, 225 participants were assigned to 1 of 4 groups: normal, media opacity only, retinal/neural disease only, and cataract plus retinal/neural disease. Participants were recruited if they were 20 years or older but were excluded if they had a neurological disorder or medication known to affect CFF. The CFF thresholds were measured for 3 stimulus sizes: 0.5 degree, 1.0 degree, and 1.5 degrees. Discrimination between groups was tested by analysis of variance and receiver operating characteristic analysis. The relationship between visual acuity and CFF in eyes without media opacity was determined by linear regression and used to predict visual outcomes in 23 eyes having cataract surgery. RESULTS: The mean age of the 225 participants was 71.4 years +/- 13.2 (SD); 134 (59.8%) were women. The normal group had 41 participants, and the other 3 groups had 61 participants each. Critical flicker fusion thresholds were reduced in retinal/neural disease but resistant to image degradation from media opacity. The 1.5-degree stimulus had 88% sensitivity and 90% specificity for discriminating groups. Visual acuity after cataract surgery was accurately predicted within +/-1 line in 43% of eyes, +/-2 lines in 83%, and +/-3 lines in 100%. All eyes with poor visual acuity (>0.50 logMAR) or dense cataract (>4.0 Lens Opacities Classification System III) were predicted within +/-2 lines. CONCLUSIONS: The CFF phenomenon effectively discriminated between subjects with and without retinal/neural disease and accurately predicted visual outcome after cataract surgery. The use of a brighter stimulus enhanced performance in cases of dense media opacity. PMID- 17276262 TI - Influence of 360-degree enhanced optic edge design of a hydrophilic acrylic intraocular lens on posterior capsule opacification. AB - PURPOSE: To compare the rate of posterior capsule opacification (PCO) with the single-piece hydrophilic acrylic foldable Rayner Centerflex 570H intraocular lens (IOL), which has a sharp optic edge design excluding the optic-haptic junction, and the Rayner C-flex 570C IOL, which has an improved 360-degree sharp edge. SETTING: Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany. METHODS: As part of a multicenter U.S. Food and Drug Administration (FDA) study, 42 patients who had implantation of a C-flex IOL in 1 eye after uneventful phacoemulsification were enrolled. Six and 12 months postoperatively, PCO was evaluated by retroillumination photographs using Evaluation of Posterior Capsule Opacification (EPCO) 2000 image-analysis software. The data were then compared with those in a matched group of patients with a Centerflex IOL who participated in a previous FDA study. RESULTS: The mean age of the patients with the C-flex IOL was 71.5 years +/- 8.2 (SD) There was a statistically significant difference in EPCO scores between the C-flex group and Centerflex group. Six months after surgery, the mean EPCO value (total IOL optic) was 0.07 +/- 0.17 in the C-flex group (n = 37) and 0.20 +/- 0.20 in the Centerflex group (n = 36) (P<.01, Wilcoxon test). By 12 months, the mean had increased to 0.16 +/- 0.20 in the C-flex group (n = 37) and 0.35 +/- 0.22 in the Centerflex group (n = 31) (P<.01, Wilcoxon test). CONCLUSIONS: The C-flex IOLs showed good functional results and significantly lower PCO formation than the earlier model Centerflex IOL. The enhanced edge of the C-flex IOL seemed to improve PCO prevention clinically. PMID- 17276264 TI - Optimum target refraction for highly and moderately myopic patients after monofocal intraocular lens implantation. AB - PURPOSE: To determine the optimum target refraction for myopic patients who want to see at both near and intermediate distances without correction after cataract surgery. SETTING: Hayashi Eye Hospital, Fukuoka, Japan. METHODS: Sixty-nine eyes of 69 patients scheduled for phacoemulsification and monofocal intraocular lens (IOL) implantation were studied. The following age groups were recruited: 50s, 60s, and 70s. With addition of a spherical lens of 1.0, 1.5, 2.0, 2.5, or 3.0 diopters (D) after best distance correction (simulation of various degrees of myopia), visual acuity at various distances was measured using the all-distance vision tester. With the assumption that visual acuity of 20/30 is necessary for near and intermediate vision, the distances at which the mean visual acuity reached 20/30 were determined. RESULTS: Six patients did not have all examinations; thus, 24 patients in the 50s group, 23 in the 60s group, and 22 in the 70s group were included in the analysis. With simulation of -1.0 or -1.5 D of myopia, sufficient near visual acuity at 0.3 m was not obtained. With -2.0 D of myopia, visual acuity better than 20/30 was obtained at 0.7 m, 0.5 m, and 0.3 m. However, with -2.5 D of myopia, visual acuity reached 20/30 at 0.5 m and 0.3 m; with -3.0 D of myopia, it reached only 20/30 at 0.3 m. There were no significant differences between the age groups in mean visual acuity from far to near distances except for intermediate visual acuity with -1.0 D and -1.5 D of myopia and for near visual acuity with -2.5 D of myopia. CONCLUSIONS: Eyes with a monofocal IOL that simulates -2.0 D of myopia achieved sufficient visual acuity for both near and intermediate distances in 3 age groups. This indicates that 2.0 D is the optimum target refraction in myopic eyes. PMID- 17276265 TI - Histopathological findings after intracorneal ring segment implantation in keratoconic human corneas. AB - PURPOSE: To evaluate histopathological changes induced in keratoconic corneas after implantation of Intacs intracorneal ring segments (Addition Technology, Inc.). SETTING: Departments of Ophthalmology and Pathology, Hospital Pellegrin, Bordeaux, France. METHODS: This retrospective study included 8 keratoconic, contact-lens-intolerant eyes of 8 patients who had penetrating keratoplasty (PKP) after removal of Intacs inserts because of a poor refractive outcome or insert extrusion. Light microscopy was performed on all specimens after conventional staining. Immunohistochemistry was performed to identify cell types located next to the tunnel using AE1/AE3 cytokeratins, CD34, vimentin, collagen IV, and alpha smooth muscle actin monoclonal antibodies. RESULTS: Conventional histology showed hypoplasia of the epithelium immediately surrounding the channel. There was no evidence of an inflammatory response or foreign-body granuloma. Keratocyte density was decreased above and below the tunnel, and collagen IV synthesis was seen in the scar area. All samples stained negatively with alpha-smooth muscle actin, indicating that myofibroblasts were not present. These changes were no longer visible when PKP was performed more than 6 months after Intacs explantation. CONCLUSIONS: Intacs induced keratocyte apoptosis, probably through a switch to a collagenous synthetic phenotype. Although histological changes seem to be entirely reversible after implant removal, longer follow-up is necessary to determine whether they accelerate corneal thinning and keratoconus progression via apoptosis and release of metalloprotease. PMID- 17276266 TI - Longitudinal study of intraocular lens exchange. AB - PURPOSE: To analyze the indications for intraocular lens (IOL) exchange, interval between the first IOL implantation and the exchange, type and mix of IOLs used, effect on vision, and frequency of complications. SETTING: Cincinnati Eye Institute-Cincinnati-Ohio-USA. METHODS: This retrospective study comprised 49 eyes of 49 adult patients who had IOL exchange between 1986 and 2002 performed by the same surgeon. The mean age was 70 years old, and 55% were women. The mean interval between surgeries was 53.8 months and the mean follow-up, 35.6 months. The patients were divided into 2 groups according to the type of IOL originally implanted: anterior chamber (AC) or posterior chamber (PC). RESULTS: There were 15 eyes with an AC IOL and 34 eyes with a PC IOL. The difference in mean age and follow-up were not statistically significant between groups. The mean interval between the primary surgery and IOL explantation was 82.3 months in the AC IOL group and 37.9 months in the PC IOL group. The main reason for IOL exchange was inflammation (53.34%) and dislocation/decentration (85.30%), respectively. The preoperative best corrected visual acuity was similar in both groups, and visual acuity was maintained or improved in 80%. Vitreous prolapse was the main intraoperative complication. CONCLUSIONS: The primary indication for IOL exchange was intraocular inflammation in patients with an AC IOL and IOL malposition in patients with a PC IOL. The results confirm the safety and positive visual outcome in this complex group of patients. PMID- 17276267 TI - Clinical effects of primary posterior continuous curvilinear capsulorhexis in eyes with single-piece hydrophilic acrylic intraocular lenses with and without haptic angulation. AB - PURPOSE: To evaluate the clinical effects of a primary posterior continuous curvilinear capsulorhexis (PCCC) on the intraocular performance of hydrophilic acrylic single-piece intraocular lenses (IOLs) with and without haptic angulation. SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: A prospective study comprised 52 patients with bilateral age-related cataract who had standard cataract surgery including a PCCC. One eye of each patient was randomized to receive a hydrophilic acrylic IOL with haptic angulation (ACR6D SE, Laboratoires Corneal) and the contralateral eye, a hydrophilic acrylic IOL without haptic angulation (C-flex 570C, Rayner). The following parameters were assessed: regeneratory posterior opacification (RPO) in the central, intermediate, and peripheral areas (scale 0 to 10); anterior capsule opacification (ACO); best corrected visual acuity (BCVA); and contrast sensitivity (CSF). RESULTS: Thirty-one patients completed the 1(1/2) year follow-up. In both IOL groups, RPO within the PCCC was slight in the central area, with a mean score of 0.33 +/- 0.84 (SD) in the angulated IOL group and 0.16 +/- 0.57 in the nonangulated IOL group (P = .29). The mean RPO score in the peripheral area was 2.07 +/- 1.37 and 2.35 +/- 1.45, respectively (P = .12). The difference between the central and peripheral areas was 1.74 in the angulated IOL group (P<.00001) and 2.19 in the nonangulated IOL group (P<.00001). Haptic deformation occurred in 9 eyes (29%) with an angulated IOL and no eye with a nonangulated IOL. There was significantly more ACO in the nonangulated IOL group (P = .012). There were no significant differences in BCVA or CSF between the 2 groups. CONCLUSIONS: Creating a PCCC led to significantly lower RPO intensity within the PCCC area than in the peripheral area in eyes with hydrophilic acrylic IOLs with and without haptic angulation. Haptic angulation had no apparent significant influence on the intensity of RPO or on BCVA and CSF. Haptic deformation may occur in hydrophilic IOLs with angulated haptics. PMID- 17276268 TI - Postcataract endophthalmitis: incidence and microbial isolates in a United Kingdom region from 1996 through 2004. AB - PURPOSE: To investigate the incidence of endophthalmitis after cataract surgery, analyze the microbiologic spectrum of infecting organisms, and assess the diagnostic utility of an anterior chamber paracentesis and vitreous biopsy. SETTING: United Kingdom tertiary referral center used by 13 operating suites. METHODS: A retrospective noncomparative consecutive series comprised 105 postcataract endophthalmitis cases. RESULTS: The annual mean incidence of endophthalmitis over the study period was 0.099% (101/101 920) [corrected] and there was no significant increase in the incidence during the study. The culture positive rate was 58.1% (61/105). Gram-positive microbes were isolated in 93.4% of cases (57/61), with coagulase-negative staphylococci accounting for 62.3% (38/61). Anterior chamber taps yielded positive cultures in 25.7% of cases, and vitreous biopsy was positive in 53.4%. CONCLUSIONS: The incidence of endophthalmitis in this region of the United Kingdom remained stable, with gram positive microbes accounting for 93.4% of the isolates. A combination of anterior chamber tap and vitreous biopsy should be performed in suspected cases of endophthalmitis. PMID- 17276269 TI - Reducing the risk for endophthalmitis after cataract surgery: population-based nested case-control study: endophthalmitis population study of Western Australia sixth report. AB - PURPOSE: To characterize operative and nonoperative risks for the potentially blinding complication of endophthalmitis after cataract surgery. SETTING: Ophthalmology services for the whole state of Western Australia. METHODS: This retrospective population-based nested case-control study in Western Australia covered the period between 1980 and 2000. For each of the 205 cases of endophthalmitis, 4 time-matched controls were randomly selected from all cataract operations performed in the state. Conditional logistic regression was used to estimate multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk factors of interest. RESULTS: Wound location, suturing the wound, and type of cataract operation did not affect the risk for postoperative endophthalmitis. Antibiotic prophylaxis reduced the risk, but only if given as a subconjunctival injection (OR, 0.46; 95% CI, 0.29-0.70). The risk for endophthalmitis was greater with same-day surgery (OR, 2.27; 95% CI, 1.52-3.41) than with admission the day before surgery. A concurrent eyelid procedure was a substantial risk. Surgeons within 2 years of obtaining specialist qualifications were more likely to have a case of endophthalmitis, although this was partly the result of more posterior capsule breaches. Posterior capsule breach increased the risk when it occurred in private hospitals (OR, 13.57; 95% CI, 4.00-45.99), but not in public hospitals. CONCLUSIONS: Nonoperative as well as operative factors are important in the prevention of endophthalmitis. Subconjunctival injection of antibiotics appears to be beneficial for endophthalmitis prophylaxis. The model showed that active risk management strategies designed to optimize hospitalization and chemoprophylaxis may reduce the incidence of endophthalmitis by up to 81%. PMID- 17276270 TI - Functional and anatomical outcomes of vitreoretinal surgery for posterior segment complications after elective cataract surgery. AB - PURPOSE: To assess the outcomes in patients who required 1 or more vitreoretinal interventions for posterior segment complications arising from elective uneventful cataract surgery. SETTING: Tertiary referral center, single-center study. METHODS: A retrospective interventional case series included 56 consecutive patients who were referred for surgical correction of posterior segment complications within 6 months of cataract surgery. The study period was between 1996 and 2003, and the minimum follow-up was 5 months. RESULTS: Posterior segment complications were resolved with a single surgical intervention in 40 cases (71.4%). Within 5 months of primary surgical correction, persisting or newly arising posterior segment complications were noted in 16 cases (28.6%). After a mean of 2.1 +/- 1.4 (SD) additional surgeries, the number of eyes with posterior segment problems decreased to 7 (12.5%) (P = .035). Posterior segment complications requiring more than 1 vitreoretinal intervention included retinal detachment, endophthalmitis, and choroidal hemorrhages. After primary correction surgery, the mean best corrected visual acuity increased from 0.15 +/- 0.24 to 0.37 +/- 0.33 (P = .001) after a single intervention and to 0.39 +/- 0.32 (P>.05) after additional interventions. Although the intraocular pressure (IOP) decreased from 21.8 +/- 16.6 mm Hg to 14.9 +/- 3.4 mm Hg (P = .008), 4 (7.1%) consecutive vascular optic atrophies occurred. A reduction in corneal transparency was observed in 46.4% of patients before primary surgical correction and 12.5% after primary surgical correction (P<.001). CONCLUSIONS: In many cases, posterior segment complications arising from cataract surgery could be repaired with favorable functional and anatomical outcomes by a single vitreoretinal intervention. Additional surgery, if requested, provided stabilization of the anatomical and functional outcomes. PMID- 17276271 TI - Torsional mode versus conventional ultrasound mode phacoemulsification: randomized comparative clinical study. AB - PURPOSE: To compare the intraoperative and short-term postoperative outcomes of cataract surgery performed with torsional mode and conventional ultrasound mode using the Infiniti Vision System (Alcon Laboratories). SETTING: Cataract Service, Zhongshan Ophthalmic Center, Sun-Yat-Sen University, Guangzhou, China. METHODS: In this randomized comparative study, 525 eyes were assigned to phacoemulsification by torsional mode or conventional ultrasound (US) mode. The surgery was performed by an experienced surgeon, and the outcomes were evaluated by an examiner who was masked to treatment assignments. Primary outcome measures were US time (UST), cumulative dissipated energy (CDE), and surgical complications. Patients were seen 1, 7, and 30 days after surgery. Postoperative outcome measures were the final best corrected visual acuity (BCVA) and the change in corneal clarity, central corneal thickness (CCT), and endothelial cell count. RESULTS: The US group had 262 eyes and the torsional group, 263 eyes. All patients completed the follow-up visits. In the eyes with nucleus density grades of 1, 2, 3, and 4, the mean UST was 10.25 seconds +/- 7.4 (SD), 25.14 +/- 5.5 seconds, 36.45 +/- 8.3 seconds, and 61.44 +/- 17.8, respectively, in the US group and 8.32 +/- 6.8 seconds, 18.45 +/- 7.2 seconds, 29.48 +/- 12.4 seconds, and 48.39 +/- 20.3 seconds, respectively, in the torsional group (P<.001); the mean CDE was 1.25 +/- 0.5, 4.18 +/- 1.2, 8.59 +/- 6.5, and 16.51 +/- 9.6, respectively, in the US group and 0.94 +/- 0.3, 3.13 +/- 2.7, 7.47 +/- 12.6, and 14.08 +/- 8.3, respectively, in the torsional group (P<.001). At 1 day and 7 days, the mean BCVA was 0.23 +/- 0.12 logMAR and 0.00 +/- 0.10 logMAR, respectively, in the US group and 0.18 +/- 0.11 logMAR and -0.08 +/- 0.05 logMAR, respectively, in the torsional group (P<.001). At 30 days, the mean BCVA was 0.10 +/- 0.07 logMAR and -0.12 +/- 0.06 logMAR in the US group and the torsional group, respectively (P>.01). At 1 day and 7 days, the mean CCT was 625 +/- 80 microm and 568 +/- 37 microm, respectively, in the US group and 601 +/- 35 microm and 559 +/- 40 microm, respectively, in the torsional group (P<.001). At 30 days, the mean CCT was 531 +/- 30 microm in the US group and 529 +/- 39 microm in the torsional group (P>.01). At 7 days and 30 days, the mean central corneal endothelial cell count was 2135 +/- 858 cells/mm(2) and 2084 +/- 527 cells/mm(2), respectively, in the US group and 2004 +/- 656 cells/mm(2) and 1953 +/- 615 cells/mm(2), respectively, in the torsional group (P<.001). CONCLUSION: The torsional mode may provide more effective lens removal with a lower level of phacoemulsification time and energy. PMID- 17276272 TI - Safety and efficacy of topical anesthesia combined with a lower concentration of intracameral lidocaine in phacoemulsification: paired human eye study. AB - PURPOSE: To assess the safety and efficacy of phacoemulsification under a topical anesthesia combined with intracameral lidocaine 0.5%. SETTING: Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, China. METHODS: A prospective randomized double-blind study was designed in which patients had phacoemulsification performed under topical anesthesia (4 drops of nonpreserved lidocaine 2%) with 0.15 mL intracameral placebo (balanced salt solution) in 1 eye (Group 1) and topical anesthesia with intracameral nonpreserved lidocaine 0.5% in the other eye (Group 2). Endothelial changes, including cell density, coefficient variation of cell size, and percentage of hexagonal cells, were measured by noncontact specular microscopy. Preoperative and postoperative best corrected visual acuity was also documented. The degree of pain throughout surgery was ranked on a 10-point visual analog pain scale. RESULTS: Thirty-three patients were recruited. There was no significant difference in preoperative and postoperative mean endothelial parameters between the 2 groups. Furthermore, mean endothelial cell loss was similar. Mild or no pain (score 0 to 1) was reported by 48.5% in Group 1 and 90.9% in Group 2. Patients reported less pain with combined topical and intracameral lidocaine anesthesia (P = .001, Mann-Whitney test). Vision was significantly improved in both groups. However, 1 patient in Group A developed vitreous loss as a result of involuntary eye movement. CONCLUSION: Combining topical anesthesia with intracameral lidocaine 0.5% [corrected] anesthesia was safe and effective in phacoemulsification with intraocular lens implantation. PMID- 17276273 TI - Prognostic factors for strabismus surgery after cataract surgery. AB - PURPOSE: To evaluate the clinical features of strabismus that present after cataract surgery and determine the motor and sensory results after surgical correction of the strabismus. SETTING: Department of Ophthalmology, the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. METHODS: Thirty-one patients who had strabismus surgery after cataract surgery between January 1996 and June 2004 were included in the study. The clinical features of strabismus and the factors contributing to successful strabismus surgery results were retrospectively analyzed. Sensory functional tests were performed postoperatively. RESULTS: Fifteen patients (48.4%) had exotropia. The types of cataract included traumatic (35.5%), congenital (32.3%), and senile (25.8%). Prolonged deviation was the statistically significant factor contributing to final alignment (P = .023). Fourteen of 31 patients had stereoacuity measurement; all achieved a stereoacuity of 3000 seconds of arc. Five of the 14 patients (35.7%) had better than 200 seconds of arc. CONCLUSIONS: The anatomical results and sensory function of the patients were generally good. When appropriate, surgical intervention to treat strabismus after cataract surgery should be offered, and this is important for restoration of fusion. PMID- 17276274 TI - Suture-related complications after congenital cataract surgery: Vicryl versus Mersilene sutures. AB - PURPOSE: To evaluate 10-0 polyester sutures (Mersilene) and 10-0 absorbable polyglactin sutures (Vicryl) for small-incision congenital cataract surgery. SETTING: Goldschleger Eye Institute, Sheba Medical Center, Tel-Aviv University, Tel-Aviv, Israel. METHODS: A retrospective review comprised 51 patients (70 eyes) who had small-incision congenital cataract extraction and intraocular lens implantation between 1999 and 2005. Surgery was done using Mersilene sutures or Vicryl sutures. Retinoscopy and a careful examination for suture-related complications were done 1 week after surgery and then every month for 6 months. The sutures were removed in cases of local tissue reaction but not for high postoperative astigmatism. The t test was used to evaluate postoperative astigmatism and the Fisher exact test, to evaluate the difference in the incidence of suture-related complications. RESULTS: The patients' age ranged from 2 months to 15 years. Ten cases (18%) of corneal vascularization occurred in the Mersilene group during the 6-month follow-up period. This necessitated suture removal, after which 1 incident of endophthalmitis occurred. In contrast, no suture-related complications were noted in the Vicryl group during that time. The difference in the incidence of complications between the 2 groups approached statistical significance (P = .07). Mean astigmatism 1 week postoperatively was 2.3 diopters (D) +/- 2.1 (SD) in the Mersilene group, which was significantly higher than in the Vicryl group (mean 1.4 +/- 1.1 D) (P = .038). However, the mean astigmatism decreased to less than 1.0 D in both groups during the 6-month follow-up period. CONCLUSION: Vicryl sutures are recommended for small-incision congenital cataract surgery. PMID- 17276275 TI - Phacoemulsification cataract extraction and intraocular lens implantation in patients with uveitis. AB - PURPOSE: To analyze the outcomes of phacoemulsification cataract extraction and intraocular lens (IOL) implantation in patients with uveitis. SETTING: Miyata Eye Hospital, Miyakonojo, Miyazaki, Japan. METHODS: The records of 95 patients (131 eyes) with uveitis who had phacoemulsification cataract extraction and IOL implantation between 1990 and 2001 were retrospectively examined. The postoperative visual outcomes and complications were analyzed. RESULTS: The mean age of the 36 men and 59 women was 61.7 years (range 30 to 87 years) At the final follow-up examination, 111 eyes (84.7%) had improved visual acuity and 97 eyes (74.0%) had a final visual acuity of 0.5 or better. Patients with Behcet's disease had significantly worse visual outcomes than patients with other clinical etiologies of uveitis such as human T-lymphotropic virus type 1 uveitis and Vogt Koyanagi-Harada disease. In 17 eyes (13.0%), relapse of intraocular inflammation occurred within 6 months after surgery; the rate of relapse was highest in patients with Behcet's disease (35.2%). Posterior synechias occurred in 8 eyes (6.1%), pupillary capture in 1 eye (0.8%), intraocular pressure elevation in 11 eyes (8.4%), and cystoid macula edema in 8 eyes (6.1%). In 31 eyes (23.7%), posterior capsule opacification required neodymium:YAG capsulotomy. CONCLUSIONS: The outcomes of phacoemulsification cataract extraction and IOL implantation in patients with uveitis were satisfactory. Patients with Behcet's disease related to intraocular inflammation, however, appeared to have a higher risk for complications and therefore worse outcomes than patients with other clinical etiologies of uveitis. PMID- 17276277 TI - Bilateral methicillin-resistant Staphylococcus aureus keratitis after photorefractive keratectomy. AB - A 52-year-old woman with a history of liver transplantation developed bilateral corneal infiltrates 1 week after uneventful photorefractive keratectomy (PRK). Cultures grew methicillin-resistant Staphylococcus aureus (MRSA), resistant to fluoroquinolone antibiotics. The infections responded to topical vancomycin and resolved bilaterally over 3 weeks. Three months postoperatively, the uncorrected visual acuity (UCVA) was 20/20 in the right eye and 20/25 in the left eye; the best spectacle-corrected visual acuity (BSCVA) was 20/20 in both eyes. During the course of treatment, the patient reported chronic intermittent prophylactic use of oral ciprofloxacin. While fluoroquinolones typically provide excellent postoperative coverage, Staphylococcus organisms have a growing antibiotic resistance to fluoroquinolones, and MRSA may become a more prevalent organism in corneal infections. Chronic subtherapeutic fluoroquinolone use can increase the mutational resistance of Staphylococcus to fluoroquinolone and methicillin. The patient's frequent hospital visits placed her at high risk for MRSA colonization. This case represents the fifth reported case of MRSA keratitis after PRK. PMID- 17276276 TI - Protective effect of free-radical scavengers on corneal endothelial damage in phacoemulsification. AB - PURPOSE: To examine the role of the water-soluble antioxidants glutathione and ascorbic acid in the irrigating solution on corneal endothelial cells following exposure to high-intensity ultrasound energy. SETTING: Goldschleger Eye Research Institute, Sheba Medical Center, Tel-Aviv University, Tel Aviv, Israel. METHODS: Thirty-two rabbit eyes were subjected to prolonged exposure to the phacoemulsification device in the anterior chamber. The eyes were divided into 4 groups that differed only in the composition of the irrigating solution applied to the eyes: balanced salt solution (BSS) BSS Plus BSS containing additional soluble components including glutathione, BSS with 10(-3) M of oxidized glutathione (GSSG), and BSS with 10(-2) M of ascorbic acid. Specular microscopy was performed preoperatively and 1 week after surgery. RESULTS: The BSS group exhibited the highest endothelial cell loss (19.3%), followed by the BSS Plus group (10.6%), the GSSG group (5.2%), and the ascorbic acid group (0.9%). An overall difference was found between the groups (F = 11.046, P<.0001), and all groups demonstrated a statistically significant difference from the control BSS group (P<.02, P = .001, and P<.0001, respectively). CONCLUSIONS: Damage to the cornea is largely due to the free radicals generated by high-intensity ultrasound energy during phacoemulsification. Adding the antioxidants ascorbic acid and GSSG to the irrigation solution significantly reduced the endothelial corneal cell damage. Ascorbic acid in the concentration of 10(-2) M had the highest protective effect; thus, it should be evaluated for clinical use. PMID- 17276278 TI - Bilateral ciliary sulcus implantation of secondary piggyback multifocal intraocular lenses. AB - Ciliary sulcus implantation of secondary multifocal intraocular lenses (IOLs) is an uncommon procedure. We describe a young pseudophakic patient with monofocal IOLs who achieved a high level of satisfaction following bilateral implantation of multifocal IOLs. They were used successfully to correct a residual refractive error for distance vision and to provide spectacle-independence for near vision. Postoperative symptoms such as glare were not problematic. PMID- 17276279 TI - Diffuse lamellar keratitis associated with gonococcal keratoconjunctivitis 3 years after laser in situ keratomileusis. AB - A 29-year-old man presented with a 5-day history of a red eye with a purulent discharge. Three years previously, he had undergone laser in situ keratomileusis elsewhere. A diagnosis of gonococcal keratoconjuntivitis was made clinically and confirmed with culture. The patient subsequently developed diffuse lamellar keratitis (DLK). The keratoconjunctivitis and DLK resolved with antibiotic therapy and topical steroids. The cause and effect relationship of these 2 uncommon events is of interest. PMID- 17276280 TI - Medical considerations before refractive surgery retreatment. AB - We report a case of a significant hyperopic shift 2 years after myopic photorefractive keratectomy with an interim of stability. The patient was an otherwise healthy man who reported a sudden change in vision when climbing to altitude. Medical considerations for refractive shifts should be looked at before retreatment is proposed. Diabetes was diagnosed in our patient; after initiation of insulin, the patient's uncorrected visual acuity returned to 20/20 in both eyes. PMID- 17276281 TI - Early opacification of a single-piece hydrophobic acrylic intraocular lens after a triple procedure. AB - We report a case in which the optic of a single-piece AcrySof acrylic (SA60AT, Alcon) intraocular lens (IOL) became opacified. A 64-year-old man had a triple procedure of vitrectomy, phacoemulsification, and IOL implantation for cataract and a dense vitreous hemorrhage in the left eye. The IOL was clear on the day after surgery, but by the third day, a dusty haze was observed on the surface due to the presence of numerous, small brown corpuscles. The IOL was removed and replaced with another SA60AT. No optic opacification occurred on the replacement IOL. Analysis of the explanted IOL indicated the presence of proteinaceous material but no calcium on the surface. Early postoperative opacification of a single-piece acrylic SA60AT IOL might occur in combined cataract and vitreous surgery, even in eyes in which the posterior capsule is intact and there are no operative complications. PMID- 17276282 TI - Rapidly progressive idiopathic lenticular astigmatism. AB - A myopic 43-year-old woman with early nuclear sclerotic cataract developed more than 11.0 diopters (D) of astigmatism over a 6-month period. This was found to be lenticular in origin. Phacoemulsification with intraocular lens implantation was performed, resulting in residual astigmatism of 0.75 D. To our knowledge, this is the first case of rapidly progressive lenticular astigmatism in an otherwise healthy eye with early nuclear sclerotic cataract. PMID- 17276283 TI - Aggressive small choroidal melanoma presenting as a dense cataract. AB - A 58-year-old woman with an aggressive, invasive, small post-equatorial choroidal melanoma presented with progressively blurred vision and a dense cataract in the affected eye. During phacoemulsification surgery, heavily pigmented retrolental vitreous was identified. Fine needle aspiration biopsy revealed heavily pigmented epithelioid cells without diagnostic features of malignancy. Small epithelioid type choroidal melanoma (2.5 mm x 2.5 mm x 1.5 mm) was confirmed following enucleation. Diffuse preretinal space seeding, vitreous infiltration, forward spreading of tumor cells into the lens capsule and trabecular meshwork resulted in a complicated cataract. PMID- 17276284 TI - Iris damage by inadvertent cannula injection. AB - Iris damage occurred in 2 patients due to the inadvertent forceful injection of a cannula. Despite luer lock syringes, the J-shaped cannula was injected during cortical removal in one eye and during hydration of the incision at the end of the procedure in the second eye. Iris damage should be added to the growing list of injuries that can result from cannula-related complications. PMID- 17276285 TI - Opacification of Array SA40N silicone multifocal intraocular lens. AB - We report opacification of 2 multifocal intraocular lenses (IOLs). Patients with these IOLs may be more likely to require IOL explantation than those with monofocal IOLs. PMID- 17276286 TI - Cystoid macular edema following photorefractive keratectomy complicated by presumptive infectious keratitis. AB - A 71-year-old man developed cystoid macular edema (CME) following photorefractive keratectomy (PRK). He had a history of CME following cataract surgery in both eyes, which had responded well to topical steroid and nonsteroidal antiinflammatory drops. The cataract surgery in the left eye had resulted in a hyperopic surprise, with secondary anisometropia and visual discomfort. For this reason, the patient elected to have PRK. Three weeks after the procedure, he returned, complaining of visual loss. Optical coherence tomography and fluorescein angiography confirmed the presence of CME. This responded well to topical and sub-Tenon's corticosteroids and nonsteroidal antiinflammatory drops. PMID- 17276287 TI - S-fold implantation technique for the AcrySof intraocular lens. PMID- 17276288 TI - Clear corneal incision with trypan-blue-coated blades. PMID- 17276290 TI - Safety of neodymium:YAG laser posterior capsulotomy in phacovitrectomy surgery. PMID- 17276289 TI - Instructions after routine phacoemulsification cataract surgery with clear corneal incision. PMID- 17276291 TI - Topical phenylephrine in laser in situ keratomileusis. PMID- 17276294 TI - Competence in nursing practice: A controversial concept--A focused review of literature. AB - The competency-based approach to education, training and assessment has surfaced as a key policy in industrialised nations. Following the transition of nurse preparation to the higher education sector the need to attenuate the tension of interests between employer and educator arose. While the competency-based approach has the potential to fulfil this, the application of competence to nursing is controversial and little consensus exists on definition. This paper synthesises a significant volume of literature relating to the acceptability and definition of the concept of competence with regard to nursing practice. Subsequent to a focused review of literature, problems inherent to the definition and utilisation of the concept of nursing competence are discussed. Because nursing requires complex combinations of knowledge, performance, skills and attitudes, a holistic definition of competence needs to be agreed upon and operationalised. This could facilitate greater acceptance of the concept and also underpin the development of competency standards and the tools required for the assessment of such. PMID- 17276293 TI - Breast cancer in the elderly: histological, hormonal and surgical characteristics. AB - The characteristics, menstrual risk factors and surgical therapy of 187 consecutive patients more than 70 years of age (mean: 75.9) were investigated and compared with those of 609 patients less than 70 years of age (mean: 53.9). There was no difference in stage, size, state of axillary nodes, grade, histological types, Ki-67, vascular invasion, estrogen receptor rate, and HER-2/neu (+) rate. Positive progesterone receptor rate was higher in older patients (54.7% vs. 63.1%). Tumors were larger (p=0.01) and their stage higher (p=0.014) in patients more than 80 years of age. All menstrual risk factors were similar in the two groups. Positive familial history was more frequent in patients <60 years. Significantly more young patients used hormone replacement therapy (HRT) (21.8 vs. 8.6%). Older patients underwent less breast-conserving surgery (36.1 vs. 55.1%), and less axillary lymph node dissection (ALND) (69.7 vs. 84.9%). We conclude that breast cancer characteristics and menstrual risk factors are similar in the two age groups. PMID- 17276295 TI - The influence of heart rate on gated SPECT images. PMID- 17276296 TI - Primary cardiac lymphoma detected by myocardial perfusion imaging: case report. PMID- 17276298 TI - Regarding the virtues and limitations of combining myocardial perfusion SPECT data acquired by diverse methods. PMID- 17276300 TI - Cardiac magnetic resonance versus SPECT: are all noninfarct myocardial regions created equal? PMID- 17276299 TI - The troponin conundrum: clarification through stress myocardial perfusion SPECT. PMID- 17276301 TI - Attenuation correction: to be or not to be. PMID- 17276302 TI - SPECT attenuation correction: an essential tool to realize nuclear cardiology's manifest destiny. AB - Single photon emission computed tomography (SPECT) myocardial perfusion imaging has attained widespread clinical acceptance as a standard of care for cardiac patients. Yet, physical phenomena degrade the accuracy of how our cardiac images are visually interpreted or quantitatively analyzed. This degradation results in cardiac images in which brightness or counts are not necessarily linear with tracer uptake or myocardial perfusion. Attenuation correction (AC) is a methodology that has evolved over the last 30 years to compensate for this degradation. Numerous AC clinical trials over the last 10 years have shown increased diagnostic accuracy over non-AC SPECT for detecting and localizing coronary artery disease, particularly for significantly increasing specificity and normalcy rate. This overwhelming evidence has prompted our professional societies to issue a joint position statement in 2004 recommending the use of AC to maximize SPECT diagnostic accuracy and clinical usefulness. Phantom and animal studies have convincingly shown how SPECT AC recovers the true regional myocardial activity concentration, while non-AC SPECT does not. Thus, AC is also an essential tool for extracting quantitative parameters from all types of cardiac radionuclide distributions, and plays an important role in establishing cardiac SPECT for flow, metabolic, innervation, and molecular imaging, our manifest destiny. PMID- 17276303 TI - Attenuation correction in cardiac SPECT: the boy who cried wolf? PMID- 17276304 TI - Impact of coronary calcium score on diagnostic accuracy of multislice computed tomography coronary angiography for detection of coronary artery disease. AB - BACKGROUND: The impact of the coronary calcium score on the diagnostic accuracy of multislice computed tomography (MSCT) to detect obstructive coronary stenoses remains controversial. METHODS AND RESULTS: We examined 41 patients (mean Agatston score, 340 +/- 530 [range, 0-2546]) with coronary artery disease with 16 slice MSCT and 60 patients (mean Agatston score, 446 +/- 877 [range, 0-6264]) with 64-slice MSCT. MSCT scans were analyzed with invasive coronary angiography (CA) as the standard of reference. Lesions with luminal narrowing of 50% or greater were considered obstructive. In total, 9% and 2% of uninterpretable segments were excluded from analysis in patients examined with 16- and 64-slice MSCT, respectively. On a segment basis, the percentage of false-negative segments in the groups with Agatston scores of 0 to 100, 101 to 400, and greater than 400 with 16-slice MSCT were 0%, 5.3%, and 2.9% (P = .0005), respectively; other comparisons of false-positive and false-negative segments were not significant. The sensitivity and specificity on a vessel and patient basis with 16- and 64 slice MSCT were not significantly different in different calcium score groups. CONCLUSIONS: A slight impact of coronary calcium was observed on the diagnostic accuracy of 16-slice MSCT CA on a segment basis, with no significant impact on a vessel and patient basis. No significant impact of coronary calcium was observed on the diagnostic accuracy of 64-slice MSCT CA on a segment, vessel, or patient basis. PMID- 17276305 TI - Combined quantitative supine-prone myocardial perfusion SPECT improves detection of coronary artery disease and normalcy rates in women. AB - BACKGROUND: We sought to determine the diagnostic performance of a recently developed combined supine-prone quantification algorithm for myocardial perfusion single photon emission computed tomography (MPS) for the detection of coronary artery disease (CAD) in women. METHODS AND RESULTS: Consecutive MPS scans of women without known CAD and coronary angiography within 3 months of MPS (n = 168) and with a low likelihood of CAD (n = 291) were considered. Total perfusion deficit (TPD) was automatically derived for supine (S-TPD), prone (P-TPD), and combined prone-supine (C-TPD) data sets. The low-likelihood patients were grouped by bra cup size (A/B, n = 102; C, n = 101; and D, n = 88). The areas under the receiver operator characteristic curves for S-TPD, P-TPD, and C-TPD were 0.84 +/- 0.03, 0.88 +/- 0.03, and 0.90 +/- 0.03, respectively. C-TPD had a higher specificity than S-TPD and P-TPD for identification of CAD (stenosis > or =70%) without compromising sensitivity (61%, 76%, and 94% for S-, P-, and C-TPD, respectively; P < .0005 vs S-TPD and P < .05 vs P-TPD). Normalcy rates were higher for C-TPD than for S-TPD or P-TPD. CONCLUSIONS: Combined supine-prone quantitative MPS in women yields significantly increased specificity and normalcy rates without compromising sensitivity for the detection of CAD compared with standard analysis. PMID- 17276306 TI - Prognostic value of SPECT myocardial perfusion imaging in patients with elevated cardiac troponin I levels and atypical clinical presentation. AB - BACKGROUND: We determined the prognostic value of myocardial perfusion imaging (MPI) in patients with atypical clinical presentations and unexpected elevation of cardiac troponin I (cTnI) levels. METHODS AND RESULTS: In 156 consecutive patients with atypical presentations for acute coronary syndromes (ACS) and elevated cTnI levels undergoing MPI within 30 days, rates of all-cause mortality (100% follow-up; median follow-up, 611 days) and 6-month cardiac death and nonfatal myocardial infarction (96% follow-up; median follow-up, 167 days) were determined. The mean age of the patients was 68 +/- 14 years. The majority of the study cohort (96%) was at low to intermediate clinical risk for ACS (Thrombolysis in Myocardial Infarction score for unstable angina/non-ST-segment elevation myocardial infarction <5). The overall event rate was high, with 45 deaths (28.8%). There were 13 cardiac deaths/nonfatal myocardial infarctions in 6 months (8.3%). A normal MPI result was associated with a high event-free survival rate, whereas an abnormal MPI result was associated with a 3-fold and 7-fold higher risk of all-cause mortality and 6-month cardiac events, respectively. An abnormal MPI result was an independent predictor of all-cause death. CONCLUSIONS: In patients with cTnI elevation and a low to intermediate risk for ACS, a normal MPI result portends a good prognosis. Patients with abnormal MPI results have a higher 6-month cardiac event rate and a worse survival rate. PMID- 17276307 TI - Quantitation of infarct size in patients with chronic coronary artery disease using rest-redistribution Tl-201 myocardial perfusion SPECT: correlation with contrast-enhanced cardiac magnetic resonance. AB - BACKGROUND: Rest and rest-redistribution thallium 201 myocardial perfusion single photon emission computed tomography (SPECT) (MPS) has been incompletely validated in patients for determination of the total amount of scarred myocardium. We sought to determine whether rest or redistribution Tl-201 MPS provides an accurate determination of infarct size as defined by delayed contrast-enhanced cardiac magnetic resonance (CMR). METHODS AND RESULTS: We studied patients (n = 44) with chronic coronary artery disease referred for rest-redistribution Tl-201 MPS, who were also studied by contrast-enhanced CMR within 3 +/- 4 days. Patients were considered retrospectively based on a series of patients referred for clinically indicated MPS. Defect size, as a percent of left ventricular mass (% LV), was determined by quantitative perfusion SPECT (QPS) and compared with the volume of delayed hyperenhancement on contrast-enhanced CMR, normalized to LV mass. Infarct size varied from 0% to 43% LV. Rest QPS defect size correlated with the amount of nonviable myocardium assessed by contrast-enhanced CMR (r = 0.76; mean difference, 4.3% +/- 8.0% LV). When delayed thallium data were considered, redistribution QPS was superior to rest QPS for determination of infarct size (redistribution r = 0.90; mean difference, 2.4% +/- 5.2% LV; P = .03 vs rest). CONCLUSION: Rest-redistribution Tl-201 MPS provides a more accurate measurement of total infarct size than rest-only Tl-201 MPS and correlates with contrast enhanced CMR. PMID- 17276308 TI - Diagnostic value of left ventricular function after stress and at rest in the detection of multivessel coronary artery disease as assessed by electrocardiogram gated SPECT. AB - BACKGROUND: Although transient left ventricular (LV) dilation is a well-known marker for extensive coronary artery disease (CAD), few studies have performed quantitative analysis of LV function after stress and at rest to detect extensive CAD. METHODS AND RESULTS: Poststress and resting gated single photon emission computed tomography (SPECT) was performed in 175 patients with suspected CAD. All of the patients underwent coronary angiography within 3 months of gated SPECT. In the 83 patients with multivessel CAD, the summed difference score was greater (9.2 +/- 7.0 vs 3.3 +/- 4.0, P < .0001), the poststress increase in end-systolic volume (ESV) was larger (7.0 +/- 8.0 mL vs -0.8 +/- 4.7 mL, P < .0001), and the poststress increase in ejection fraction (EF) was less (-4.7% +/- 5.4% vs -0.4% +/- 4.5%, P < .0001) than in the 92 patients with insignificant or single-vessel CAD. In the detection of multivessel CAD, a summed difference score of 9 or greater showed a sensitivity of 46% and specificity of 90%, whereas an increase in ESV of 5 mL or greater and a decrease in EF of 5% or greater after exercise had a sensitivity of 66% and 52%, respectively, and specificity of 87% and 83%, respectively. The multivariate discriminant analysis revealed that the combination of poststress increase in ESV, summed difference score, and diabetes mellitus best identified multivessel CAD, with a sensitivity of 72% and specificity of 84% (chi(2), 81.7). CONCLUSIONS: The addition of poststress and at rest LV functional analysis by use of gated SPECT to conventional perfusion analysis helps to better identify patients with multivessel CAD. PMID- 17276309 TI - Prognostic value of gated SPECT in patients with left bundle branch block. AB - BACKGROUND: The aim of this study was to assess the prognostic value of quantitative gated technetium 99m tetrofosmin single photon emission computed tomography (SPECT) imaging in patients with left bundle branch block (LBBB). METHODS AND RESULTS: We followed up 101 consecutive patients with LBBB using Tc 99m tetrofosmin gated SPECT imaging. The mean follow-up was 1.24 years (maximum, 2.48 years). Hard endpoints were all-cause death and acute myocardial infarction. Event-free survival curves were obtained. Optimal cutoff points for left ventricular (LV) volumes and LV ejection fraction (EF) to predict outcome were determined by receiver operating characteristic curve analysis. Of the patients, 94 had an abnormal study. Fifteen hard events occurred (thirteen deaths). Perfusion abnormalities were similar for patients with or without events. For LV function parameters, the survival curves were maximally separated when we used cutoff values of 160 mL or greater for end-diastolic volume (P = .019 and hazard ratio [HR] of 1.04 for hard events, P = .024 and HR of 1.04 for all-cause death), 100 mL or greater for end-systolic volume (P = .043 and HR of 1.04 for hard events, P = .062 and HR of 1.04 for all-cause death), and lower than 35% for LVEF (P = .013 and HR of 0.81 for hard events, P = .047 and HR of 0.81 for all-cause death). CONCLUSION: By use of quantitative gated SPECT imaging, LBBB patients with an end-diastolic volume of 160 mL or greater, end-systolic volume of 100 mL or greater, or LVEF lower than 35% are at increased risk for subsequent cardiac events. PMID- 17276310 TI - Alignment of 3-dimensional cardiac structures in O-15-labeled water PET emission images with mutual information. AB - BACKGROUND: The aim of this study was to develop a method to correct the heart position between two oxygen 15-labeled water cardiac positron emission tomography (PET) image sets to be able to use the equivalent regions of interest for the quantification of the perfusion values in the same myocardial segments. METHODS AND RESULTS: Independent component analysis was applied to the dynamic image sets (simulated phantom and 6 rest-pharmacologic stress and 10 rest-rest image sets of healthy female volunteers) acquired at different time points to separate the cardiac structures (ventricles and myocardium). The separated component images from independent component analysis from the 2 studies of the same individual were aligned with a normalized mutual information-based registration method. The alignment parameters were applied to position the regions of interest in the floating image sets for calculation of the myocardial blood flow values. In the rest case the mean myocardial blood flow value was 0.76 +/- 0.12 mL x g(-1) x min(-1) for the manual method and 0.79 +/- 0.10 mL x g(-1) x min(-1) for the proposed method (by use of the right ventricle component in the alignment), and in the stress case these values were 3.39 +/- 0.70 mL x g(-1) x min(-1) and 4.01 +/- 0.71 mL x g(-1) x min(-1), respectively. No statistically significant difference was found between the methods. CONCLUSION: In the tests with the phantom and patient images the alignment of cardiac structures was shown to be successful. The alignment could be done without the use of information from the myocardial compartment. PMID- 17276311 TI - Assessment of pulmonary thromboendarterectomy by tomographic electrocardiogram gated equilibrium radionuclide angiocardiography compared with electron beam computed tomography. AB - BACKGROUND: Successful thromboendarterectomy for chronic thromboembolic pulmonary hypertension promptly improves right ventricular (RV) function by decreasing RV volume and increasing ejection fraction (EF). Single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) has been validated as a measure of RV and left ventricular (LV) volume and EF. METHODS AND RESULTS: Nine patients with chronic thromboembolic pulmonary hypertension underwent electron beam computed tomography (EBCT) and SPECT ERNA cardiac studies before and after thromboendarterectomy. EBCT and SPECT ERNA measures of RV and LV volume and EF were compared. Before thromboendarterectomy, EBCT and SPECT ERNA RV and LV volumes and RV EF were similar. LV EF was within the normal range with both methods but was slightly greater (P = .004) when measured by EBCT (mean +/- SD, 0.61 +/- 0.08) compared with SPECT ERNA (0.54 +/- 0.10). Thromboendarterectomy measured by EBCT and SPECT ERNA produced marked similar and significant decreases in RV end-systolic (-72 +/- 59 mL vs -58 +/- 25 mL) and end diastolic (-75 +/- 85 mL vs -76 +/- 32 mL) volumes and similar slight increases in RV EF (0.12 +/- 0.07 vs 0.05 +/- 0.06). Slight decreases in mean LV end systolic (-19 +/- 23 mL vs -5 +/- 13 mL, P = .05) and end-diastolic (-32 +/- 53 mL vs -9 +/- 31 mL, P = .21) volumes occurred, with little change in mean LV EF (0.05 +/- 0.07 vs 0.00 +/- 0.10). CONCLUSIONS: SPECT ERNA is an accurate method for measuring RV and LV volume and EF before and after thromboendarterectomy. PMID- 17276312 TI - Early imaging in heart failure: exploring novel molecular targets. PMID- 17276314 TI - Extracardiac abnormalities on myocardial perfusion imaging in a patient undergoing liver transplantation. PMID- 17276313 TI - Diagnostic and prognostic value of BMIPP imaging. PMID- 17276315 TI - Transient perfusion and motion abnormalities in takotsubo cardiomyopathy. PMID- 17276316 TI - Comment on "The role of the translation table in cardiac image display". PMID- 17276320 TI - Self-efficacy and norm measures for lunch fruit and vegetable consumption are reliable and valid among fifth grade students. AB - OBJECTIVE: To determine the reliability and validity of a questionnaire measuring fruit and vegetable (FV) self-efficacy and social norms during school lunch among 5th graders. DESIGN: In this cross-sectional study, students completed lunch food records and a psychosocial questionnaire measuring school lunch FV self-efficacy and social norms regarding consumption during the fall and spring semesters. Test retest reliability was assessed between fall and spring semesters. The measurement model was cross-validated in the spring data. SETTING: One middle school in Houston, Texas. PARTICIPANTS: 275 fifth graders in the 1998 fall semester and 262 of these fifth graders in the 1999 spring semester. MAIN OUTCOME MEASURES: FV consumption and psychosocial variables. ANALYSES: Principal components analyses, confirmatory factor analyses and bivariate correlations. RESULTS: Three scales were identified: Fruit Self-Efficacy, Vegetable Self Efficacy, and FV Social Norms. FV self-efficacy were positively correlated with low-fat vegetable and fruit consumption. Social norms were positively correlated with total vegetable, low-fat vegetable, fruit and total FV consumption. CONCLUSIONS AND IMPLICATIONS: Self-efficacy and norms for eating FV at school lunch are related to lunch FV consumption. Increasing self-efficacy and social norms about consuming FV at school appears to be important targets to improve FV consumption. PMID- 17276321 TI - Training dietitians in basic motivational interviewing skills results in changes in their counseling style and in lower saturated fat intakes in their patients. AB - OBJECTIVE: To test if basic training for dietitians in motivational interviewing (MI) resulted in changes in dietitians' counseling style and improvements in their patients' diet and risk parameters. DESIGN: A randomized controlled trial. SETTING: 9 home-care organizations in the Netherlands. PARTICIPANTS: 37 dietitians, 209 baseline patients, and 142 follow-up diabetes patients. INTERVENTION: Dietitians were randomly allocated to receive basic training in motivational interviewing (MI dietitians, n=18) or not (control dietitians, n=19). MAIN OUTCOME MEASURES: Counseling style of dietitians; total self-reported saturated fat, fruit, and vegetable intake, measured body mass index (BMI), waist circumference, and glycated hemoglobin (Hemoglobin A(1c), HbA(1c)) of patients. ANALYSIS: Analyses of variance and multiple linear regression analyses. Alpha = .05 RESULTS: MI dietitians were significantly more empathetic, more often showed reflection during consultations, and were more likely than control dietitians to let their patients talk for the majority of the consultation. Patients of MI dietitians had significantly lower saturated fat intake levels at posttest compared to patients of control dietitians. No effects on HbA(1c), BMI, and waist circumference were found. CONCLUSIONS AND IMPLICATIONS: Basic training in MI changed the dietitians' counseling style and resulted in lower saturated fat intakes in their patients. PMID- 17276322 TI - Use of a weight loss index for evaluating weight management in adults. AB - OBJECTIVE: A quantitative method for evaluating weight loss using the body mass index (BMI) standard 25, during part or the entire weight loss continuum, was designed and tested. DESIGN: Weight Loss Index (WLI) represents the area under the curve of the graphical representation of the weight loss attempt; x axis=time, y-axis=BMI, BMI standard=25.0. SETTING: Reliability of the WLI for 1-5 years of weight loss efforts in 50 overweight (BMI=39.1+/-7.6) patients was evaluated by comparing their calculated WLI to a weight loss ratio, derived using a traditional 2-point comparison. Weight Loss Index sensitivity was tested by sending weight loss scenarios to obesity experts, who were asked to rank success of each weight loss attempt within a scenario. Expert rankings were compared to WLI rankings. VARIABLES MEASURED: Age, weight, height, BMI, WLI. ANALYSIS: Dependent t-test for WLI versus pre-post BMI values. Spearman's correlation coefficients for WLI versus expert rankings. Significance, P<.05. RESULTS: Weight Loss Index better described weight loss attempts for overweight adults than did traditional 2-point comparisons. Obesity experts could not distinguish differences in weight loss success among patients with fluctuating weights, but the WLI categorically ranked these individuals. CONCLUSIONS AND IMPLICATIONS: Using the WLI, researchers and clinicians can compare the weight loss attempts within an individual, among individuals, and among groups of individuals against the standard BMI reference of 25.0. PMID- 17276323 TI - Trying to find the quickest way: employed mothers' constructions of time for food. AB - OBJECTIVE: The study sought to develop an understanding of how employed mothers constructed time for food provisioning for themselves and their families. DESIGN: A grounded theory approach and semistructured, in-depth interviews. SETTING: A metropolitan area of approximately 1 million people in the northeastern United States. PARTICIPANTS: Thirty-five low-wage employed mothers were purposively recruited to vary in occupation, race/ethnicity, education, household composition, and age using workplace, community, convenience, and snowball sampling. PHENOMENON OF INTEREST: Low-wage employed mothers' constructions of time for food. ANALYSIS: Interview transcripts were analyzed using the constant comparative method. RESULTS: Most mothers expressed feelings of time scarcity. Mothers described 3 timestyles that reflected how they constructed time. Timestyles reflected mothers' experiences of strain and time scarcity, usual time management strategies, and sense of control over time. Mothers prioritized feeding their children but wanted to complete meals quickly in order to move on to other tasks. CONCLUSIONS AND IMPLICATIONS: Recognizing issues of time scarcity and individual differences of timestyles and time management strategies can help researchers better understand food choice practices and assist practitioners in identifying practical food provisioning strategies for low-wage employed mothers. Food policies and recommendations should be evaluated for their relevance to the time scarcity and work strain issues that these mothers faced. PMID- 17276325 TI - Food insecurity and gender are risk factors for obesity. AB - OBJECTIVE: Examine relationships between adult obesity, childhood overweight, and food insecurity. DESIGN: Cross-sectional retrospective study. SETTING: Community settings in Hartford, Connecticut. PARTICIPANTS: Convenience sample of 200 parents and their 212 children, aged 2-12. MAIN OUTCOME MEASURES: Adult obesity (Body Mass Index [BMI] > 30), childhood overweight (BMI-for-age > 95(th) percentile), and household food security (U.S. Department of Agriculture module). ANALYSIS: Chi-square tests between weight status and socioeconomic characteristics. Multinomial regression analyses to determine risk factors for adult obesity and childhood overweight. RESULTS: Over half of parents (51%) were obese, and almost one-third of children (31.6%) were overweight. Over half of households were food insecure. Food insecure adults were significantly more likely to be obese as those who were food secure (Odds Ratio [OR]=2.45, p = .02). Being a girl and having an obese parent doubled the likelihood of children being overweight (OR=2.56, P = .01; OR=2.32, P = .03). Children with family incomes below 100% of poverty were half as likely to be overweight as those with higher incomes (OR=.47, P = .05). Food insecurity did not increase odds of childhood overweight. CONCLUSIONS AND IMPLICATIONS: Obesity prevention programs and policies need to address food insecurity and gender as key risk factors. PMID- 17276324 TI - Food spending behaviors and perceptions are associated with fruit and vegetable intake among parents and their preadolescent children. AB - OBJECTIVE: Examine the role of food spending behaviors and perceptions on fruit and vegetable intake among preadolescent children and their parents. DESIGN: Cross-sectional study. SETTING: Metropolitan city. PARTICIPANTS: Five hundred fifty-five parent/child dyads participating in the PARADE study. More than 50% of participants were African American and nearly 40% of households were low income. VARIABLES MEASURED: Body mass index calculated from child anthropometric data and parents' self-reported height and weight. Adult and child fruit and vegetable intake, annual household income, and food purchase behavior and perceptions obtained from parent questionnaire. ANALYSIS: Analysis of variance used to identify differences in means at P<.05 level. RESULTS: No statistically significant differences in fruit and vegetable intake by income status were observed. Children in households spending the least per week on groceries consumed fewer daily fruits and vegetables. Perceptions of cost of fruits and vegetables were also found to be significantly associated with fruit and vegetable intake among children and parents. CONCLUSIONS AND IMPLICATIONS: Public health efforts to raise awareness of the relatively low cost of fruits and vegetables should be continued. These efforts may be complemented with policy strategies that make fruits and vegetables more viable options for low-income households. PMID- 17276326 TI - Development of a decision tree to determine appropriateness of NVivo in analyzing qualitative data sets. AB - A decision tree was developed to determine when NVivo is an appropriate tool for qualitative analysis. NVivo, a qualitative analysis software package, was used to analyze interviews of 204 Asian, Hispanic, and white parents in 12 states. The experience provided insight into issues that should be considered when deciding to use the software. NVivo can enhance the qualitative research process, quickly process queries, and expand analytical avenues. Before using, however, the following must be considered: training time, establishing inter-coder reliability, number and length of documents, coding time, coding structure, use of automated coding, and possible need for separate databases or additional supporting software. PMID- 17276327 TI - Peer-led theater as a nutrition education strategy. PMID- 17276328 TI - Use of the standardized patient model to develop nutrition counseling skills. PMID- 17276329 TI - Persistence by nutrition education researchers facilitates nutrition education practice. PMID- 17276330 TI - Chk1: a double agent in cell cycle checkpoints. AB - Two cell cycle surveillance systems--the DNA damage checkpoint and the spindle checkpoint--guard against genomic instability. The protein kinase Chk1 is a well established signal transducer in the DNA damage checkpoint. In this issue of Developmental Cell, Zachos et al.(2007) present evidence to indicate that Chk1 also plays a critical role in the spindle checkpoint, suggesting an interplay between the DNA damage and spindle checkpoints. PMID- 17276331 TI - Putting transcription repression and protein destruction in pRb's pocket. AB - The tumor suppressor function of the retinoblastoma protein (pRb) is historically attributed to inhibition of E2F gene transcription. In a recent issue of Nature Cell Biology, Binne and colleagues show that pRB is physically linked to the active anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase, suggesting that pRB-mediated tumor suppression may also function by directing the local degradation of E2F targets, including Skp2 (Binne et al., 2006). PMID- 17276332 TI - Micromanaging alternative splicing during muscle differentiation. AB - A recent report in Genes & Development by Boutz et al. (2007) demonstrates that muscle specific microRNAs (miRNAs) downregulate the alternative splicing regulator nPTB during skeletal muscle differentiation to control a potential network of splicing transitions. The results illustrate how two modes of posttranscriptional regulation combine to direct skeletal muscle development. PMID- 17276333 TI - A matter of some importins: nuclear transport factors in ES cell maintenance and differentiation. AB - A recent paper in Nature Cell Biology reports an unexpected role for nuclear transport proteins in triggering the differentiation of ES cells. The authors show how switching of importin-alpha subtypes exerts a selective gate-keeping function in the nuclear import of key transcription factors that regulate stem cell maintenance and differentiation. PMID- 17276334 TI - Ran and Rac in mouse eggs: cortical polarity and spindle positioning. AB - Polar body formation in eggs proceeds through two extreme asymmetric divisions, requiring precise coordination between spindle position and the polarized acto myosin cortex. Two new studies appearing in this issue of Developmental Cell implicate the small GTPases Ran and Rac in cortical polarity of the mouse egg. PMID- 17276336 TI - Bcl-2-regulated calcium signals as common mediators of both apoptosis and autophagy. AB - The calcium ion, a major intracellular second messenger, is a known mediator of apoptosis and is regulated by the antiapoptotic protein Bcl-2. A paper by Hoyer Hasen et al. (2007) in the current issue of Molecular Cell indicates that calcium also mediates the induction of macroautophagy in a Bcl-2 regulated fashion and identifies a signaling pathway through which calcium exerts its action. These intriguing findings provoke speculation as to how a cell decides to undergo either apoptosis or macroautophagy in response to calcium signals. PMID- 17276335 TI - Epigenetic arbitration of cell fate decisions: tipping the bias. AB - Epigenetic modifications of nucleosomal histones are thought to mediate transcriptional states and impose heritable instructions upon differentiation. In a paper of Torres-Padilla and colleagues in Nature, protein modification at arginine residues, namely of core histones, is correlated with cell fate determination at the 4-cell stage in the mouse embryo. This represents the first link of global epigenetic instructions associated with specification of early cell lineages. PMID- 17276337 TI - Endothelium-microenvironment interactions in the developing embryo and in the adult. AB - The vascular endothelium is best known for its role in oxygen and nutrient delivery to the various tissues. Growing evidence supports a far more complex role in tissue homeostasis. In particular, reciprocal interactions between endothelial cells and the local microenvironment may regulate organ development and pattern formation. Such interactions appear to be important also in the adult, in normal and pathological conditions. PMID- 17276338 TI - Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis. AB - To clarify the mechanisms that support the continuity of actively cycling tissues of long-lived organisms, we investigated the composition of a mouse spermatogenic stem cell system by pulse-chase of the undifferentiated spermatogonia, the population responsible for stem cell functions, in combination with transplantation and regeneration assays after pulse-labeling. We demonstrate that in addition to "actual stem cells," which are indeed self-renewing, a second population ("potential stem cells") also exists, which is capable of self renewing but do not self-renew in the normal situation. Potential stem cells rapidly turn over in normal testes, suggesting that they belong to the transit amplifying, rather than the dormant, population. During the long natural course, actual stem cells are occasionally lost and compensated for by progeny of their neighbors. In this process, potential stem cells are postulated to shift their modes from transit amplification to self-renewal, thus playing an essential role to ensure spermatogenesis integrity. PMID- 17276339 TI - Whole-somite rotation generates muscle progenitor cell compartments in the developing zebrafish embryo. AB - Somites are transient, mesodermally derived structures that give rise to a number of different cell types within the vertebrate embryo. To achieve this, somitic cells are partitioned into lineage-restricted domains, whose fates are determined by signals secreted from adjacent tissues. While the molecular nature of many of the inductive signals that trigger formation of different cell fates within the nascent somite has been identified, less is known about the processes that coordinate the formation of the subsomitic compartments from which these cells arise. Utilizing a combination of vital dye-staining and lineage-tracking techniques, we describe a previously uncharacterized, lineage-restricted compartment of the zebrafish somite that generates muscle progenitor cells for the growth of appendicular, hypaxial, and axial muscles during development. We also show that formation of this compartment occurs via whole-somite rotation, a process that requires the action of the Sdf family of secreted cytokines. PMID- 17276340 TI - BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms. AB - The adult, virgin mammary gland is a highly organized tree-like structure formed by ducts with hollowed lumen. Although lumen formation during pubertal development appears to involve apoptosis, the molecular mechanisms that regulate this process are not known. Here, we demonstrate that disruption of the BH3-only proapoptotic factor Bim in mice prevents induction of apoptosis in and clearing of the lumen in terminal end buds during puberty. However, cells that fill the presumptive luminal space are eventually cleared from the adjacent ducts by a caspase-independent death process. Within the filled Bim(-/-) ducts, epithelial cells are deprived of matrix attachment and undergo squamous differentiation prior to clearing. Similarly, we also detect squamous differentiation in vitro when immortalized mammary epithelial cells are detached from the matrix. These data provide important mechanistic information on the processes involved in sculpting the mammary gland and demonstrate that BIM is a critical regulator of apoptosis in vivo. PMID- 17276341 TI - RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination. AB - The forkhead transcription factor, DAF-16, a downstream target of the insulin/IGF I signaling pathway in C. elegans, is indispensable both for lifespan regulation and stress resistance. The molecular mechanisms involved in regulating DAF-16 transcriptional activation remain undefined. Here, we have identified an E3 ubiquitin ligase, RLE-1 (regulation of longevity by E3), which regulates aging in C. elegans. Disruption of RLE-1 expression in C. elegans increases lifespan; this extension of lifespan is due to elevated DAF-16 protein but not to changes of daf 16 mRNA levels. We have also found that RLE-1 catalyzes DAF-16 ubiquitination, leading to degradation by the proteasome. Elimination of RLE-1 expression in C. elegans causes increased transcriptional activation and sustained nuclear localization of DAF-16. Overexpression of DAF-16 in rle-1 mutants increases worm lifespan, while disruption of DAF-16 expression in rle-1 mutants reverses their longevity. Thus, RLE-1 is an E3 ubiquitin ligase of DAF-16 that regulates C. elegans aging. PMID- 17276342 TI - Chk1 is required for spindle checkpoint function. AB - The spindle checkpoint delays anaphase onset in cells with mitotic spindle defects. Here, we show that Chk1, a component of the DNA damage and replication checkpoints, protects vertebrate cells against spontaneous chromosome missegregation and is required to sustain anaphase delay when spindle function is disrupted by taxol, but not when microtubules are completely depolymerized by nocodazole. Spindle checkpoint failure in Chk1-deficient cells correlates with decreased Aurora-B kinase activity and impaired phosphorylation and kinetochore localization of BubR1. Furthermore, Chk1 phosphorylates Aurora-B and enhances its catalytic activity in vitro. We propose that Chk1 augments spindle checkpoint signaling and is required for optimal regulation of Aurora-B and BubR1 when kinetochores produce a weakened signal. In addition, Chk1-deficient cells exhibit increased resistance to taxol. These results suggest a mechanism through which Chk1 could protect against tumorigenesis through its role in spindle checkpoint signaling. PMID- 17276343 TI - Kinesin-mediated transport of Smad2 is required for signaling in response to TGF beta ligands. AB - During vertebrate development, Activin/Nodal-related ligands signal through Smad2, leading to its activation and accumulation in the nucleus. Here, we demonstrate that Smad2 constantly shuttles between the cytoplasm and nucleus both in early Xenopus embryo explants and in living zebrafish embryos, providing a mechanism whereby the intracellular components of the pathway constantly monitor receptor activity. We have gone on to demonstrate that an intact microtubule network and kinesin ATPase activity are required for Smad2 phosphorylation and nuclear accumulation in response to Activin/Nodal in early vertebrate embryos and TGF-beta in mammalian cells. The kinesin involved is kinesin-1, and Smad2 interacts with the kinesin-1 light chain subunit. Interfering with kinesin activity in Xenopus and zebrafish embryos phenocopies loss of Nodal signaling. Our results reveal that kinesin-mediated transport of Smad2 along microtubules to the receptors is an essential step in ligand-induced Smad2 activation. PMID- 17276344 TI - The master switch gene sex-lethal promotes female development by negatively regulating the N-signaling pathway. AB - Notch (N) signaling is used for cell-fate determination in many different developmental contexts. Here, we show that the master control gene for sex determination in Drosophila melanogaster, Sex-lethal (Sxl), negatively regulates the N-signaling pathway in females. In genetic assays, reducing Sxl activity suppresses the phenotypic effects of N mutations, while increasing Sxl activity enhances the effects. Sxl appears to negatively regulate the pathway by reducing N protein accumulation, and higher levels of N are found in Sxl(-) clones than in adjacent wild-type cells. The inhibition of N expression does not depend on the known downstream targets of Sxl; however, we find that Sxl protein can bind to N mRNAs. Finally, our results indicate that downregulation of the N pathway by Sxl contributes to sex-specific differences in morphology and suggest that it may also play an important role in follicle cell specification during oogenesis. PMID- 17276345 TI - Cortical beta-catenin and APC regulate asymmetric nuclear beta-catenin localization during asymmetric cell division in C. elegans. AB - In C. elegans, Wnt signaling regulates a number of asymmetric cell divisions. During telophase, WRM-1/beta-catenin localizes asymmetrically to the anterior cortex and the posterior daughter's nucleus. However, cortical WRM-1's functions are not known. Here, we use a membrane-targeted form of WRM-1 to show that cortical WRM-1 inhibits Wnt signaling and the nuclear localization of WRM-1. These functions are mediated by APR-1/APC, which regulates WRM-1 nuclear export. We also show that APR-1 as well as PRY-1/Axin and Dishevelled homologs localize asymmetrically to the cortex. Our results suggest a model in which cortical WRM-1 recruits APR-1 to the anterior cortex before and during division, and the cortical APR-1 stimulates WRM-1 export from the anterior nucleus at telophase. Because beta-catenin and APC are localized to the cortex in many cell types in different species, our results suggest that these cortical proteins may regulate asymmetric divisions or Wnt signaling in other organisms as well. PMID- 17276346 TI - The Ran GTPase mediates chromatin signaling to control cortical polarity during polar body extrusion in mouse oocytes. AB - The molecular basis for asymmetric meiotic divisions in mammalian oocytes that give rise to mature eggs and polar bodies remains poorly understood. Previous studies demonstrated that the asymmetrically positioned meiotic chromosomes provide the cue for cortical polarity in mouse oocytes. Here we show that the chromatin-induced cortical response can be fully reconstituted by injecting DNA coated beads into metaphase II-arrested eggs. The injected DNA beads induce a cortical actin cap, surrounded by a myosin II ring, in a manner that depends on the number of beads and their distance from the cortex. The Ran GTPase plays a critical role in this process, because dominant-negative and constitutively active Ran mutants disrupt DNA-induced cortical polarization. The Ran-mediated signaling to the cortex is independent of the spindle but requires cortical myosin II assembly. We hypothesize that a Ran(GTP) gradient serves as a molecular ruler to interpret the asymmetric position of the meiotic chromatin. PMID- 17276347 TI - Rac activity is polarized and regulates meiotic spindle stability and anchoring in mammalian oocytes. AB - Mammalian meiotic divisions are asymmetrical and generate a large oocyte and two small polar bodies. This asymmetry results from the anchoring of the meiotic spindle to the oocyte cortex and subsequent cortical reorganization, but the mechanisms involved are poorly understood. We investigated the role of Rac in oocyte meiosis by using a fluorescent reporter for Rac-GTP. We find that Rac-GTP is polarized in the cortex overlying the meiotic spindle. Polarization of Rac activation occurs during spindle migration and is promoted by the proximity of chromatin to the cortex. Inhibition of Rac during oocyte maturation caused a permanent block at prometaphase I and spindle elongation. In metaphase II arrested oocytes, Rac inhibition caused the spindle to detach from the cortex and prevented polar body emission after activation. These results demonstrate that Rac-GTP plays a major role in oocyte meiosis, via the regulation of spindle stability and anchoring to the cortex. PMID- 17276348 TI - A helping hand for cytochrome p450 enzymes. AB - In this issue of Cell Metabolism, Espenshade and colleagues (Hughes et al., 2007) show that the hemoprotein Dap1/PGRMC1 forms a stable complex with several members of the cytochrome P450 superfamily of enzymes and positively regulates their activities. This action indicates an important role for Dap1/PGRMC1 in P450 catalyzed reactions, some of which are involved in the metabolism of sterols and pharmaceutical compounds. PMID- 17276349 TI - Fly foie gras: modeling fatty liver in Drosophila. AB - Lipids provide an essential source of metabolites and energy in normal development as well as during periods of food deprivation. A recent study in Drosophila (Gutierrez et al., 2007) reveals a novel role in regulating lipid metabolism for specialized cells called oenocytes that present striking functional similarities to mammalian hepatocytes. PMID- 17276350 TI - The metabolic sensor GCN2 branches out. AB - GCN2 is a sensor of amino acid deprivation that triggers a repression of global protein synthesis while simultaneously inducing translation of specific proteins. In this issue of Cell Metabolism, Guo and Cavener (2007) present a much broader role for GCN2 in controlling lipid homeostasis in response to amino acid deprivation. PMID- 17276351 TI - How do I fatten thee? Let me count the ways... AB - Glycerol-3-phosphate acyltransferase (GPAT) initiates the synthesis of triacylglycerol and phospholipids and, in the process, regulates the formation of several lipid metabolites known to be intracellular signaling molecules. The recent identification of a new GPAT isoform (Cao et al., 2006) suggests a role for GPAT isoforms in nutrient-mediated signaling. PMID- 17276352 TI - An afferent vagal nerve pathway links hepatic PPARalpha activation to glucocorticoid-induced insulin resistance and hypertension. AB - Glucocorticoid excess causes insulin resistance and hypertension. Hepatic expression of PPARalpha (Ppara) is required for glucocorticoid-induced insulin resistance. Here we demonstrate that afferent fibers of the vagus nerve interface with hepatic Ppara expression to disrupt blood pressure and glucose homeostasis in response to glucocorticoids. Selective hepatic vagotomy decreased hyperglycemia, hyperinsulinemia, hepatic insulin resistance, Ppara expression, and phosphoenolpyruvate carboxykinase (PEPCK) enzyme activity in dexamethasone treated Ppara(+/+) mice. Selective vagotomy also decreased blood pressure, adrenergic tone, renin activity, and urinary sodium retention in these mice. Hepatic reconstitution of Ppara in nondiabetic, normotensive dexamethasone treated PPARalpha null mice increased glucose, insulin, hepatic PEPCK enzyme activity, blood pressure, and renin activity in sham-operated animals but not hepatic-vagotomized animals. Disruption of vagal afferent fibers by chemical or surgical means prevented glucocorticoid-induced metabolic derangements. We conclude that a dynamic interaction between hepatic Ppara expression and a vagal afferent pathway is essential for glucocorticoid induction of diabetes and hypertension. PMID- 17276354 TI - Xanthine oxidoreductase is a regulator of adipogenesis and PPARgamma activity. AB - In an effort to identify novel candidate regulators of adipogenesis, gene profiling of differentiating 3T3-L1 preadipocytes was analyzed using a novel algorithm. We report here the characterization of xanthine oxidoreductase (XOR) as a novel regulator of adipogenesis. XOR lies downstream of C/EBPbeta and upstream of PPARgamma, in the cascade of factors that control adipogenesis, and it regulates PPARgamma activity. In vitro, knockdown of XOR inhibits adipogenesis and PPARgamma activity while constitutive overexpression increases activity of the PPARgamma receptor in both adipocytes and preadipocytes. In vivo, XOR -/- mice demonstrate 50% reduction in adipose mass versus wild-type littermates while obese ob/ob mice exhibit increased concentrations of XOR mRNA and urate in the adipose tissue. We propose that XOR is a novel regulator of adipogenesis and of PPARgamma activity and essential for the regulation of fat accretion. Our results identify XOR as a potential therapeutic target for metabolic abnormalities beyond hyperuricemia. PMID- 17276353 TI - The GCN2 eIF2alpha kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid. AB - Metabolic adaptation is required to cope with episodes of protein deprivation and malnutrition. GCN2 eIF2alpha kinase, a sensor of amino acid deficiency, plays a key role in yeast and mammals in modulating amino acid metabolism as part of adaptation to nutrient deprivation. The role of GCN2 in adaptation to long-term amino acid deprivation in mammals, however, is poorly understood. We found that expression of lipogenic genes and the activity of fatty acid synthase (FAS) in the liver are repressed and lipid stores in adipose tissue are mobilized in wild type mice upon leucine deprivation. In contrast, GCN2-deficient mice developed liver steatosis and exhibited reduced lipid mobilization. Liver steatosis in Gcn2(-/-) mice was found to be caused by unrepressed expression of lipogenic genes, including Srebp-1c and Fas. Thus, our study identifies a novel function of GCN2 in regulating lipid metabolism during leucine deprivation in addition to regulating amino acid metabolism. PMID- 17276355 TI - Menage-a-trois 1 is critical for the transcriptional function of PPARgamma coactivator 1. AB - The Cdk7/cyclin H/menage-a-trois 1 (MAT1) heterotrimer has proposed functions in transcription as the kinase component of basal transcription factor TFIIH and is activated in adult hearts by Gq-, calcineurin-, and biomechanical stress dependent pathways for hypertrophic growth. Using cardiac-specific Cre, we have ablated MAT1 in myocardium. Despite reduced Cdk7 activity, MAT1-deficient hearts grew normally, but fatal heart failure ensued at 6-8 weeks. By microarray profiling, quantitative RT-PCR, and western blotting at 4 weeks, genes for energy metabolism were found to be suppressed selectively, including targets of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1). Cardiac metabolic defects were substantiated in isolated perfused hearts and isolated mitochondria. In culture, deleting MAT1 with Cre disrupted PGC-1 function: PGC 1alpha failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4 PGC-1alpha was functionally defective, and PGC-1beta was likewise deficient. PGC 1 bound to both MAT1 and Cdk7 in coprecipitation assays. Thus, we demonstrate a requirement for MAT1 in the operation of PGC-1 coactivators that control cell metabolism. PMID- 17276356 TI - Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. AB - Cytochrome P450 enzymes are heme-dependent monoxygenases that play a central role in human physiology. Despite the numerous physiological processes that P450 enzymes impact, the electron donors P450 oxidoreductase and cytochrome b5 are the only proteins known to interact with and modulate the activity of ER microsomal P450s. Here, we report that Dap1/PGRMC1 is required for ER P450 function in yeast and humans. We show that S. pombe Dap1 is a hemoprotein that binds and positively regulates Cyp51A1 and Cyp61A1, two P450s required for sterol biosynthesis. Similarly, loss of human PGRMC1 reduces activity of Cyp51A1, blocking cholesterol synthesis and increasing production of toxic sterol intermediates. PGRMC1 stably binds Cyp51A1 and human P450s from three additional families including Cyp3A4, which metabolizes pharmaceutical compounds. These findings demonstrate that PGRMC1 is required for P450 activity and suggest that interindividual variation in PGRMC1 function may impact multiple biochemical pathways and drug metabolism. PMID- 17276359 TI - HHV-6: an underestimated virus. Proceedings of the 5th International Conference on HHV-6&7. May 1-3, 2006. Barcelona, Spain. PMID- 17276357 TI - Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. AB - Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and old rats and found that acute stimulation of AMPK-alpha(2) activity by 5'-aminoimidazole-4-carboxamide-1-beta-D ribofuranoside (AICAR) and exercise was blunted in skeletal muscle of old rats. Furthermore, mitochondrial biogenesis in response to chronic activation of AMPK with beta-guanidinopropionic acid (beta-GPA) feeding was also diminished in old rats. These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging. PMID- 17276360 TI - Apoptotic effects of Human Herpesvirus-6A on glia and neurons as potential triggers for central nervous system autoimmunity. AB - BACKGROUND: Human Herpesvirus type 6 (HHV-6A and/or HHV-6B) has been tentatively associated with multiple sclerosis (MS). However, there is currently no direct proof of pathogenicity. OBJECTIVES: To determine whether exposure to HHV-6 variants is capable of inducing programmed cell death (apoptosis) in representative cell types of the central nervous system (CNS). STUDY DESIGN: HHV 6A and HHV-6B variants were grown on human T cell lines HSB2 and MOLT-3, respectively. Human neuronal (SK-N-SH), astrocytes (CRT), and oligodendrocytes (TC620) cell lines were exposed in vitro to infected T cells in a trans-well system for up to 4 days (5x10(4) cells target cells and 2x10(6) T cells). Apoptosis was measured by a FACS-based method. RESULTS: Exposure to HHV-6A induced apoptosis in a time-dependent manner, while exposure to HHV-6B did not. Three days after exposure, apoptosis was increased compared to normalized controls, by 239% in neurons, 321% in astrocytes, and 326% in oligodendrocytes, respectively. CONCLUSIONS: This study provides the demonstration that exposure to immune cells carrying replicating HHV-6A may injure glial cells and neurons by inducing apoptosis, and direct evidence for a causal association between HHV-6A with MS and related disorders. PMID- 17276361 TI - Infection of murine oligodendroglial precursor cells with Human Herpesvirus 6 (HHV-6)--establishment of a murine in vitro model. AB - BACKGROUND: Human Herpesvirus 6 was previously demonstrated to infect human oligodendroglial precursor cells (OPCs) in vitro causing cell cycle arrest and premature differentiation with consequent loss of the precursor pool. OBJECTIVES: To develop an in vitro murine OPC model to study the cell cycle and differentiation effects of HHV-6 in more readily available, genetically well defined cells free of the risk of contamination with human herpesviruses. STUDY DESIGN: Murine OPCs were exposed to infectious HHV-6A or HHV-6B and analyzed for production of viral transcripts, particles, and replicating virus. FACS analysis and specific markers were used to evaluate effects on cell cycling and differentiation. RESULTS: HHV-6 infection of murine OPCs resulted in production of both immediate-early and some late transcripts but no replicating virus by TaqMan quantitative PCR or electron microscopy. Both a specific G1/S cell cycle arrest and premature loss of OPCs through differentiation into oligodendrocytes as previously seen with human precursors were recapitulated. CONCLUSIONS: Infection of murine OPCs by HHV-6 reproduces the critical phenotypes of cell cycle arrest and altered differentiation seen in human cells. The murine system provides a highly defined, accessible, and reproducible source of cells permitting the elucidation of specific viral and cell cycle genes involved in CNS viral infections of OPCs. PMID- 17276363 TI - Clinical parameters and HHV-6 active replication in relapsing-remitting multiple sclerosis patients. AB - BACKGROUND: Although the etiology of multiple sclerosis (MS) remains uncertain, clinical, epidemiological, and laboratory findings suggest that environmental factors may be involved in the disease. OBJECTIVE: This study was undertaken in order to investigate the possible relation of human herpesvirus-6 (HHV-6) in relapsing-remitting MS (RRMS). STUDY DESIGN: A one-year follow-up study was performed analyzing serum samples of 63 patients with RRMS and 63 healthy blood donors (HBD) by a quantitative real time PCR, to measure HHV-6 prevalence and viral load. Clinical data (starting age and EDSS increase) were collected. RESULTS: (i) We found 25.4% of RRMS patients with at least one positive serum sample along the one year follow-up. (ii) 19.1% of RRMS samples in relapse had HHV-6 active infection vs. 7.9% of RRMS samples in remission. (iii) We only found variant A. (iv) RRMS patients with HHV-6 active replication initiated the disease 1.9 years earlier, and they had a higher EDSS increase. CONCLUSIONS: A higher HHV 6A frequency of active infection seems to be related with the exacerbations in a subset of RRMS patients. Regarding the relationship between HHV-6A active infection and the clinical data in RRMS patients, further investigations are needed. PMID- 17276364 TI - Differentiated human neural stem cells: a new ex vivo model to study HHV-6 infection of the central nervous system. AB - BACKGROUND: HHV-6 is the etiologic agent of exanthem subitum, a pediatric illness that may be associated with clinical and laboratory signs of central nervous system involvement. The absence of suitable experimental models has so far hampered the elucidation of the mechanisms of HHV-6-mediated neural cell damage. Recently, the growing knowledge in neurobiology has permitted the establishment of long-term cultures of human neural stem cells (hNSC) that, by virtue of their self-renewal capacity and multipotentiality, provide a valuable tool for the study of neurodegenerative disorders. OBJECTIVES AND STUDY DESIGN: We studied the effects of HHV-6 infection in differentiated cultures of hNSC derived from the telencephalic and diencephalic regions of a 13.5 week post conception (pcw) fetal brain. The prototypic HHV-6 strain GS (subgroup A) was used. RESULTS: hNSC were differentiated ex vivo to obtain mixed cultures encompassing astrocytes, neurons and oligodendrocytes. These differentiated hNSC cultures were found to be susceptible to productive HHV-6A infection, resulting in the formation of syncytia associated with phenotypic alterations. CONCLUSION: These results demonstrate that hNSC may provide a physiologically relevant model to investigate the pathogenic role of HHV-6 in central nervous system disorders. PMID- 17276365 TI - A perspective on human herpes virus 6 (HHV-6). PMID- 17276367 TI - Is human herpesvirus-6 a trigger for chronic fatigue syndrome? AB - Chronic fatigue syndrome (CFS) is an illness currently defined entirely by a combination of non-specific symptoms. Despite this subjective definition, CFS is associated with objective underlying biological abnormalities, particularly involving the nervous system and immune system. Most studies have found that active infection with human herpesvirus-6 (HHV-6)--a neurotropic, gliotropic and immunotropic virus--is present more often in patients with CFS than in healthy control and disease comparison subjects, yet it is not found in all patients at the time of testing. Moreover, HHV-6 has been associated with many of the neurological and immunological findings in patients with CFS. Finally, CFS, multiple sclerosis and seizure disorders share some clinical and laboratory features and, like CFS, the latter two disorders also are being associated increasingly with active HHV-6 infection. Therefore, it is plausible that active infection with HHV-6 may trigger and perpetuate CFS in a subset of patients. PMID- 17276366 TI - Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue. AB - BACKGROUND: Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression. OBJECTIVES: We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir. STUDY DESIGN: Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study. RESULTS: Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients. CONCLUSION: These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect. PMID- 17276368 TI - HHV-6 and the immune system: mechanisms of immunomodulation and viral escape. AB - Clinical and experimental evidence indicates that human herpesvirus 6 (HHV-6) can interfere with the function of the host immune system through a variety of mechanisms. Both HHV-6A and B can infect, either productively or nonproductively, several types of immune cells. The primary target for HHV-6 replication, both in vitro and in vivo, is the CD4+ T lymphocyte, a pivotal cell in the generation of humoral and cell-mediated adaptive immune responses. HHV-6A, but not B, also replicates in various cytotoxic effector cells, such as CD8+ T cells, gammadelta T cells and natural killer cells. In professional antigen-presenting cells like macrophages and dendritic cells, HHV-6 infection is typically nonproductive; yet, it induces dramatic functional abnormalities, including a selective suppression of IL-12, a critical cytokine in the generation of Th1-polarized antiviral immune responses. This and other immunomodulatory effects seem to be mediated by the engagement of the primary HHV-6 receptor, CD46. Moreover, HHV-6 infection results in a generalized loss of CD46 expression in lymphoid tissue, which may lead to an aberrant activation of autologous complement. Additional mechanisms of immunomodulation by HHV-6 include alterations in cell surface receptor expression and cytokine/chemokine production. HHV-6 can also modulate influence responses through the expression of virally-encoded homologs of chemokines and chemokine receptors. By modulating specific antiviral immune responses, HHV-6 can facilitate its own spread and persistence in vivo, as well as enhance the pathogenic effects of other agents, such as human immunodeficiency virus. PMID- 17276369 TI - Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome. AB - BACKGROUND: Human herpesvirus 6 (HHV-6) and 7 (HHV-7) have been suggested as possible triggering agents for chronic fatigue syndrome (CFS). OBJECTIVES: To determine the possible association of HHV-6 and HHV-7 infections with CFS. STUDY DESIGN: The prevalence of latent/persistent and active viral infections by nPCR, characteristic of HHV-6 variants using restriction endonuclease analysis and changes of lymphocyte subsets in peripheral blood by laser flow-cytometry in 17 CFS patients was examined. In addition, 12 patients with unexplained chronic fatigue and 20 blood donors (BD) were studied. RESULTS: No difference in prevalence of latent/persistent single viral infections between the patients and BD was found but dual infection rate was significantly higher in CFS patients. Active HHV-6 and dual (HHV-6 + HHV-7) infections were detected in CFS patients only and frequency of HHV-7 reactivation was also significantly higher in these patients. HHV-6 variant B was predominant in CFS patients (12/13). The changes of immunological parameters in CFS patients with active dual infection were characterized by significant decrease of CD3+ and CD4+ T cells, significant increase of CD95+ cells and decrease of CD4+/CD8+ ratio. CONCLUSIONS: HHV-6 and HHV-7 may be involved in the pathogenesis of CFS and reactivation of both viruses may provoke changes in the phenotype of circulating lymphocytes. PMID- 17276370 TI - Human herpesvirus 6 and central nervous system disease in hematopoietic cell transplantation. AB - Human herpesvirus 6 infects virtually all children within the first few years of life and like other herpesviruses, establishes latency after primary infection. In immunocompromised hosts, especially hematopoietic cell transplant (HCT) recipients, HHV-6 has been demonstrated to reactivate frequently. This reactivation has been associated with a number of different clinical endpoints in HCT recipients, including central nervous system (CNS) disease. There have been many detailed descriptions of individual patients with HHV-6-associated encephalitis. In addition, longitudinal observational studies have established a correlation between systemic HHV-6 reactivation and CNS dysfunction. Further research is needed to define optimal diagnostic, prevention, and treatment strategies. PMID- 17276371 TI - Detection of HHV-6B in post-mortem central nervous system tissue of a post-bone marrow transplant recipient: a multi-virus array analysis. AB - BACKGROUND: HHV-6 has been implicated in a number of neurological disorders. Recent evidence has suggested high incidence of HHV-6 infection in patients (46%) undergoing allogeneic bone marrow transplant (BMT). OBJECTIVE: To investigate whether HHV-6 plays a role in the development of fatal encephalopathy in an allogeneic post-BMT patient using an unbiased approach. RESULTS: Detection of HHV 6 viral DNA sequence and RNA expression were demonstrated in fresh frozen post mortem autopsy material derived from the insular cortex using a multi-virus array platform. In addition, PCR analysis by real-time quantitative TaqMan demonstrated high viral burden in multiple brain regions tested. Sequencing analysis of PCR product confirmed the virus to be HHV-6 variant B. CONCLUSIONS: Active infection as demonstrated by expression of viral RNA and high viral load in the CNS suggest a possible pathogenic role of HHV-6 in development neurologic complications post BMT. PMID- 17276372 TI - Human herpesvirus 6B inhibits cell proliferation by a p53-independent pathway. AB - BACKGROUND: Various forms of cellular stress can activate the tumour suppressor protein p53, an important regulator of cell cycle arrest, apoptosis, and cellular senescence. Cells infected by human herpesvirus 6B (HHV-6B) accumulate aberrant amounts of p53. OBJECTIVES: The aim of this study was to investigate the role of p53 accumulation in the HHV-6B-induced cell cycle arrest. STUDY DESIGN: The role of p53 was studied using the p53 inhibitor pifithrin-a, and cells genetically deficient in functional p53 by homologous recombination. RESULTS: In response to HHV-6B infection, epithelial cells were arrested in the G1/S phase of the cell cycle concomitant with an aberrant accumulation of p53. However, the known p53 induced mediator of cell cycle arrest, p21, was not upregulated. Approximately 90% of the cells expressed HHV-6B p41, indicative of viral infection. The presence of pifithrin-a, a p53 inhibitor, did not reverse the HHV-6B-induced cell cycle block. In support of this, HHV-6B infection of p53(-/-) cells induced a cell cycle block before S-phase with kinetics similar to or faster than that observed by infection in wt cells. CONCLUSIONS: HHV-6B infection inhibited host cell proliferation concomitantly with p53 accumulation, but importantly the block in cell cycle occurred by a pathway independent of p53. PMID- 17276373 TI - Antiviral activity of diverse classes of broad-acting agents and natural compounds in HHV-6-infected lymphoblasts. AB - BACKGROUND: HHV-6 replication requires complex and poorly understood interactions between viral and cellular factors. OBJECTIVES: Several natural compounds or broad-acting pharmacological agents were studied in an attempt to discover new targets for anti-HHV-6 therapy. STUDY DESIGN: The antiviral activity was determined in human T-lymphoblasts, using HHV-6A (GS)-infected HSB-2 cells, HHV 6B (Z29)-infected MOLT-3 cells and HHV- 6B (HST)-infected MT4 cells. Virus replication was measured by CPE and qPCR assay. Foscarnet was included as the reference compound. RESULTS: Among the 15 natural compounds tested, only 'red marine algae' (an extract rich in sulfated polysaccharides) exhibited strong activity when added during virus adsorption. Among the broad-acting pharmacological agents, chloroquine, artemisinin, hypericin, ribavirin, resveratrol and glycyrrhizic acid were all inactive. Amantadine produced a reproducible inhibition of HHV-6 replication, albeit at relatively high concentrations. Except for lamotrigine, which was moderately active against HHV 6B, several antiepileptic drugs were shown to have no activity. We included several compounds which we previously described as potent HHV-6 inhibitors, i.e., the non-nucleoside inhibitor CMV423 and the acyclic nucleoside phosphonate analogues cidofovir and 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-3 deazaadenine. The latter compound exhibited remarkable anti-HHV-6 activity. CONCLUSION: Further optimization of compounds belonging to diverse classes of antiherpetic agents, for their specific action against HHV-6, is warranted. PMID- 17276374 TI - HHV-6 DNA in peripheral blood mononuclear cells after liver transplantation. AB - BACKGROUND: Human herpesvirus-6 (HHV-6) infections have been reported after liver transplantation. In this study, the detection of HHV-6 DNA in peripheral blood mononuclear cells (PBMC) was compared with HHV-6 antigenemia in liver transplant patients. OBJECTIVES: Forty-three adult liver recipients were frequently monitored by HHV-6 antigenemia test, which detects the viral antigens in PBMC, but is rather qualitative than quantitative. STUDY DESIGN: From the same PBMC specimens HHV-6 DNA was demonstrated by in situ hybridization using a biotinylated probe and quantified as positive cells/10, 000 PBMC. Altogether 330 blood specimens were analyzed. RESULTS: During the first 6 months (mean 12 days) after transplantation, 35/43 patients developed HHV-6 antigenemia. Concurrently, HHV-6 DNA-positive cells with mean peak number of 661(+/-574)/10, 000 were detected in 33/35 patients. Seven patients received ganciclovir treatment because of concurrent CMV infection with mean peak number of HHV-6 DNA-positive cells 381(+/-336) before and 34(+/-59)/10, 000 after the treatment (p = 0.03). All CMV infections responded to ganciclovir, but HHV-6 DNAemia disappeared slowly, within 79 days (mean 36 days). Without antivirals, HHV-6 DNAemia/antigenemia lasted usually longer. CONCLUSIONS: Detection of HHV-6 DNA in PBMC correlated well with HHV-6 antigenemia, and may be used in the monitoring of transplant patients. PMID- 17276375 TI - In search of effective anti-HHV-6 agents. AB - Since HHV-6, like HCMV, is a beta-herpesvirus, anti-HCMV drugs such as (val)ganciclovir, foscarnet and cidofovir may, by extrapolation, be advocated for the treatment of HHV-6 infections. At present, no prime candidate for the treatment of HHV-6 infections has been identified or even proposed, which means that the search for antiviral drugs effective against HHV-6-associated diseases should be encouraged. In essence, this search is going into two directions: nucleoside and non-nucleoside analogues. To the first category belong S2242, an N7-substituted purine acyclic derivative; A-5021, a cyclopropyl nucleoside analogue; cyclopropavir, a methylene cyclopropane analogue; lipophilic ester prodrugs of the acyclic nucleoside phosphonate cidofovir; and various other "old" and "new" acyclic nucleoside phosphonate analogues including those derived from the 2, 4-diaminopyrimidine (DAPy) skeleton. To the non-nucleoside category belong a number of quinoline-3-carboxamide, aryl sulfone, benzimidazole riboside and phenylenediamine sulfonamide derivatives which could be further optimized from a structure-activity relationship (SAR) viewpoint so as to specifically target HHV 6 replication. Also, specific protein kinase inhibitors may be pursued as anti HHV-6 agents, a representative example being the compound CMV423 which, being inhibitory to (cellular) protein tyrosine kinases, exhibits potent and selective activity against HHV-6. PMID- 17276376 TI - Human herpesvirus-6 infection in solid organ and stem cell transplant recipients. AB - HHV-6 has in recent years become recognized as a potential significant pathogen in both solid organ and stem cell transplant recipients. HHV-6 infections are common after transplantation regardless of the utilized diagnostic technique. Several different clinical manifestations have been described including fever, bone marrow suppression, encephalitis, skin rash, and hepatitis. The most important end-organ disease is encephalitis in stem cell transplant recipients that has been reported to have a mortality of at least 40%. HHV-6 is also considered an immunomodulatory and immunosuppressive virus that may facilitate super-infections with other opportunistic pathogens such as CMV and fungal infections and thereby contribute to overall mortality. No established therapy exists but both ganciclovir and foscarnet have been reported to have in vitro and in vivo efficacy against HHV-6. PMID- 17276377 TI - Human herpesvirus 6 reactivation and inflammatory cytokine production in patients with drug-induced hypersensitivity syndrome. AB - BACKGROUND: Human herpesvirus 6 (HHV-6) reactivation has been suggested to modify the clinical features of drug induced hypersensitivity syndrome (DIHS). However, mechanisms for viral reactivation and modification of the clinical features remain unclear. OBJECTIVE: To determine whether cytokines play an important role in viral reactivation and modification of the clinical features. STUDY DESIGN: We examined the kinetics of serum cytokines and viral load in HHV-6 infections of six patients with DIHS. RESULTS: HHV-6 infection occurred three to four weeks after the onset of disease. Elevated TNF-alpha and IL-6 levels were observed to precede HHV-6 infection in four of the six patients. Although high levels of IL-6 were observed in samples collected prior to HHV-6 infection, the amounts of this cytokine significantly decreased to undetectable levels during viral infection in five of the six patients. Subsequently, serum IL-6 levels were increased after viral infection in five patients. IL-1beta levels were also increased at the time of viral infection in three of the six patients. Neither IL-4 nor IFN-gamma could be detected in any of the samples. CONCLUSION: These results demonstrate that cytokines play an important role in HHV-6 reactivation in patients with DIHS. PMID- 17276378 TI - Anchoring in time estimation. AB - In two experiments, an anchoring account of the misestimation of future task duration was tested. This account states that such misestimation occurs because previous task duration serves as an anchor for predictions, leading to underestimation when a longer task follows a shorter one and overestimation when a shorter task follows a longer one. Before estimating the duration of a focal task, participants selected a figure (anchor) of a longer or shorter duration produced by other participants in previous research on the same task (Experiment 1) or a different task (Experiment 2). In both experiments, misestimation differed according to the relative duration of the anchor to the focal task. Underestimation occurred with the shorter anchor and overestimation occurred with the longer one, suggesting that estimates were distorted in the direction of the anchors. This finding is discussed in relation to the role of prior task experience in moderating this anchoring effect. PMID- 17276379 TI - Comparison of ancient and modern Clonorchis sinensis based on ITS1 and ITS2 sequences. AB - In 1975, an ancient corpse buried in 167 BC was found at Jiangling County, Hubei Province of China. The eggs of Clonorchis sinensis found in the gall bladder of the corpse were preserved well. In the present paper, we extracted the genomic DNA from the ancient eggs and modern eggs, respectively, and the internal transcribed spacer 1 and 2 (ITS1 and ITS2) at ribosomal RNA genes were studied. The results show that ITS2 sequences from the ancient sample were identical with those from modern samples, but in ITS1 differences in 15 nucleotide positions were found between the ancient and modern samples. The results demonstrated that it is possible to extract and sequence DNA from ancient parasite eggs. The ITS1 sequence obtained differed from all modern ones available to date. This might indicate sequence divergence through time, or might reflect a sequence polymorphism that may eventually be found also in modern samples. PMID- 17276380 TI - The outcome of manuscripts submitted to the American Journal of Ophthalmology between 2002 and 2003. AB - PURPOSE: To investigate the outcome of manuscripts submitted to the American Journal of Ophthalmology (AJO) between July 23, 2002 and December 31, 2003. DESIGN: Observational series. METHODS: Data were collected on all Full-Length Articles and Brief Reports submitted to the AJO. Data were recorded for rejected or withdrawn manuscripts about the date of submission and decision, category of decision, type of article, manuscript region of origin, alternate journal of manuscript, date of publication, and impact factor and immediacy index of the subsequent journal. Corresponding data were collected from the manuscripts accepted over the same period. The Advanced PubMed online database was searched to determine if the rejected or withdrawn manuscripts were published elsewhere. The impact factor and the immediacy index of the journal of the subsequent journal was then recorded and compared with those of the AJO, using the year 2004 for comparison. RESULTS: Of 2,026 manuscripts submitted, 1,444 were rejected by the AJO or withdrawn by the authors and 50% of these were subsequently published elsewhere in a PubMed listed journal. The rejected or withdrawn articles were typically published in lower impact journals, most commonly in general ophthalmology journals in the author's region or in subspecialty journals, although several were published in higher impact journals. The 727 articles were published in 94 different journals and usually with an extended delay. CONCLUSIONS: Rejection of a manuscript by the AJO does not preclude publication, but rejected manuscripts are published more often in journals that serve a smaller readership and are cited less frequently, although exceptions exist. PMID- 17276381 TI - Underdevelopment of optic radiation in children with amblyopia: a tractography study. AB - PURPOSE: To detect the abnormalities of the optic radiation (OR) in children with amblyopia by diffusion tensor imaging (DTI) and tractography. DESIGN: Prospective, nonrandomized clinical trial. METHODS: Fourteen children with amblyopia and 14 normally sighted children underwent DTI scanning. After the ORs were reconstructed by using tractography algorithm, voxels through which the anterior parts of ORs passed were determined for their values of fractional anisotropy (FA). The paired t test was applied to compare their mean FA values of right OR and left OR in the control group. For the amblyopia group, analysis of variance was conducted to determine the effect of laterality and vision status on the FA values. In addition, the voxel numbers of anterior and posterior parts of both ORs were calculated. The Student t test was used to compare the average FA of bilateral ORs and voxel numbers between the two groups. RESULTS: Comparison demonstrated left-higher-than-right asymmetry in both amblyopic children and normal children. We found no significant difference of average FA between the amblyopic group (0.4832 +/- 0.0225) and control group (0.4770 +/- 0.0273). Voxel numbers of the anterior parts of both ORs were not significantly different between the two groups, whereas voxel numbers of their posterior parts in the controls were more than that of amblyopic children. CONCLUSION: Tractography showed more voxels in the posterior ORs of normal children than in the amblyopic children, indicating that normal children have better development of the ORs. The underdevelopment of the ORs might reflect the dysfunction of visual cortex in children with amblyopia. PMID- 17276382 TI - Epithelial herpetic simplex keratitis recurrence and graft survival after corneal transplantation in patients with and without atopy. AB - PURPOSE: To compare the incidence of herpes simplex virus (HSV) epithelial recurrence and graft survival after penetrating keratoplasty (PK) in patients with and without self-reported atopy. DESIGN: Retrospective cohort comparative study. METHODS: SETTING: Cornea Service, Wills Eye Hospital. STUDY POPULATION: Patients who presented with previously diagnosed ocular HSV between March 2003 and March 2004 and who underwent primary PK for ocular HSV at the Cornea Service. From the 58 patients invited, 49 patients (50 eyes) were included. Nine patients were ineligible in accordance with the exclusion criteria: no active classic HSV episode before PK, immunosuppression, less than one year of follow-up, previous history of PK before presentation at the Service. Eligible patients filled out a questionnaire regarding their history of atopic disease, considering: presence of allergic rhinitis, asthma, or atopic dermatitis. Ocular history was obtained through chart review. main outcome measures: Incidence of epithelial HSV recurrences and corneal graft survival in both groups. RESULTS: Each group (atopic and nonatopic) included 25 eyes. The atopic patients had a mean incidence of 0.07 episode/eye year (SD +/- 0.9) compared with 0.12/eye year (standard deviation [SD] +/- 0.21) in the nonatopics (P = .002). At 10 years of follow-up, the survival rate in the atopics was of 92% and in the nonatopics was of 79% (P = .88). CONCLUSIONS: Nonatopics had significantly more epithelial recurrences after PK compared to atopics; however, both groups presented low incidences of recurrences and high graft survival rates. PMID- 17276383 TI - Identification of prion inhibitors by a fluorescence-polarization-based competitive binding assay. PMID- 17276384 TI - Ultrasensitive biochemical sensors based on microcantilevers of atomic force microscope. PMID- 17276386 TI - Characterization of liposomes coated with S-layer proteins from lactobacilli. AB - The stability of liposomes coated with S-layer proteins from Lactobacillus brevis and Lactobacillus kefir was analyzed as a previous stage to the development of a vaccine vehicle for oral administration. The interactions of the different S layer proteins with positively charged liposomes prepared with soybean lecithin or dipalmitoylphosphatidylcholine were studied by means of the variation of the Z potential at different protein-lipid ratios, showing that both proteins were able to attach in a greater extent to the surface of soybean lecithin liposomes. The capacity of these particles to retain carboxyfluorescein or calcein by exposure to bile salts, pancreatic extract, pH change and after a thermal shock showed that both S-layer proteins increased the stability of the liposomes in the same magnitude. The non-glycosylated protein from L. brevis protects more efficiently the liposomes at pH 7 than those from L. kefir even without treatment with glutaraldehyde. PMID- 17276385 TI - Uptake and release of [(3)H]GABA in human dental pulp. AB - The purpose of this study was to determine whether (a) an uptake system for gamma aminobutyric acid (GABA) exists in human dental pulp, (b) GABA can be released from nerves in this tissue, and (c) GABA(B) autoreceptors modulate release of this transmitter. Segments of vital pulp were incubated in [(3)H]GABA (0.1-10 microM) for up to 120 min, washed, and the retained [(3)H] extracted and assayed. Some tissues were treated with GABA uptake inhibitors (nipecotic acid or NO-711) prior to incubation. At concentrations of 0.1 and 1.0 microM the uptake of [(3)H]GABA was saturated after 90 min of incubation. At 10 microM, at least two uptake compartments were apparent, and the amount of [(3)H]GABA retained was five fold greater than 0.1 microM. The uptake inhibitors reduced [(3)H]GABA accumulation by more than 80%. In the release study, pulp was incubated in [(3)H]GABA (0.5 microM) for 90 min, and superfused with Krebs solution containing NO-711 (5 microM). Electrical stimulation increased the overflow of [(3)H]; a GABA(B) autoreceptor agonist (baclofen) inhibited, whilst an antagonist, Sch 50911, enhanced this release. The effects of baclofen were reversed by Sch 50911. These results imply that GABA can be taken up and bound firmly in compartments within human dental pulp, GABA can be released from isolated pulp segments by electrical stimulation, and this release is modulated by GABA(B) autoreceptors. PMID- 17276387 TI - Drive for thinness, affect regulation and physical activity in eating disorders: a daily life study. AB - Using Ecological Momentary Assessment, the within patient associations between drive for thinness, emotional states, momentary urge to be physically active and physical activity were studied in 32 inpatients with an eating disorder. Participants received an electronic device and had to indicate at nine random times a day during 1 week their momentary drive for thinness, positive and negative emotional states and their urge to be physically active and physical activity. Multilevel analyses indicated that patients with higher mean levels for urge to be physically active were characterized by lower body mass index (BMI) and chronically negative affect whereas patients with higher mean levels for physical activity were characterized by lower BMI and higher dispositions for drive for thinness. In addition, within patient relations between drive for thinness and urge to be physically active were moderated by BMI and chronically negative affect whereas within patient relations between drive for thinness and physical activity were moderated by BMI. Finally, also positive emotional states were significantly associated with physical activity within patients. By using a daily process design, characteristics of physical activity were revealed that have not been identified with assessment methods that have a lower time resolution. PMID- 17276388 TI - Molecular pathways of angiogenesis inhibition. AB - A large body of evidence now demonstrates that angiostatic therapy represents a promising way to fight cancer. This research recently resulted in the approval of the first angiostatic agent for clinical treatment of cancer. Progress has been achieved in decrypting the cellular signaling in endothelial cells induced by angiostatic agents. These agents predominantly interfere with the molecular pathways involved in migration, proliferation and endothelial cell survival. In the current review, these pathways are discussed. A thorough understanding of the mechanism of action of angiostatic agents is required to develop efficient anti tumor therapies. PMID- 17276389 TI - VEGF is critical for spontaneous differentiation of stem cells into cardiomyocytes. AB - Cardiomyocyte regeneration is limited in adult life and is not sufficient to compensate for cell loss with myocardial infarction. Hence, the identification of a useful source of cardiomyocyte progenitors is of great interest for possible use in regenerative therapy. In this study, we isolated stem cells derived from human subcutaneous adipose tissue. The expression of Nkx2.5 and GATA-4 can be observed by PCR directly after extraction and during cultivation in some of these cells. Cardiac Troponin T and myosin light chain-2v become positive after 12 days of cultivation. To define respective factors responsible for spontaneous differentiation, we measured VEGF level in ADSC conditioned medium. Our data showed that ADSC secrete significant amount of VEGF (283.5pg per microgram DNA) and that anti-VEGF receptor antibodies blocked the cardiac differentiation. In conclusion, we demonstrated the spontaneous differentiation of human subcutaneous adipose-derived stem cells into a cardiomyocyte phenotype under standard culturing conditions. PMID- 17276390 TI - Neonatal growth cartilage: equine tissue specific gene expression. AB - Endochondral bone formation is an important process in development and growth of the skeleton; still many of the mechanisms of growth cartilage remain unknown. The aim of this study was to identify genes specifically expressed in growth cartilage by constructing a subtraction cDNA library of the articular-epiphyseal cartilage complex from neonatal foal. Two hundred and eighty-four differently expressed clones, representing five novel and 37 known genes, were detected by subtraction hybridization. The tissue specificity of these genes was verified by reverse Northern analysis, and tissue distribution was determined by Northern blot analysis. Genes were classified according to predicted function. The largest functional group was the extracellular matrix, followed by transcription, signalling, cytokines and growth factors. Gremlin, Angiopoietin-like 7, and Small acidic protein have previously not been detected in growth cartilage. Based on earlier descriptions of these genes, they may represent interesting candidates in future studies of developmental orthopedic disorders. PMID- 17276391 TI - The Prp19/Pso4 core complex undergoes ubiquitylation and structural alterations in response to DNA damage. AB - Prp19/Pso4, a U-box containing E3 ligase, has a demonstrated role in pre-mRNA splicing, but has also been implicated in both yeast and mammalian cells as having a direct role in DNA damage processing. In this report, we provide further evidence in support of this latter assertion. We show that hPrp19 forms an ubiquitylated oligomeric species that is resistant to disruption by SDS gel electrophoresis under nonreducing conditions suggesting that is mediated by a thiolester between ubiquitin and a cysteine residue in Prp19. The level of this species is significantly enhanced upon treatment of cells with DNA damaging agents, and its association with chromatin is increased. In addition, hPrp19 is known to form a stable core complex with Cdc5L, Plrg1, and Spf27; however, ubiquitylated hPrp19 fails to interact with either Cdc5L or Plrg1 indicating that DNA damage can induce profound alterations to the hPrp19 core complex. Finally, we show that overexpression of hPrp19 in human cells provides a pro-survival affect in that it reduces the levels of apoptosis observed after exposure of cells to DNA damage. PMID- 17276392 TI - Structural characterization of the photoswitchable fluorescent protein Dronpa C62S. AB - The photoswitching behavior of green fluorescent proteins (GFPs) or GFP-like proteins is increasingly recognized as a new technique for optical marking. Recently, Ando and his colleagues developed a new green fluorescent protein Dronpa, which possesses the unique photochromic property of being photoswitchable in a non-destructive manner. To better understand this mechanism, we determined the crystal structures of a new GFP Dronpa and its mutant C62S, at 1.9 Angstroms and 1.8 Angstroms, respectively. Determination of the structures demonstrates that a unique hydrogen-bonding network and the sulfur atom of the chromophore are critical to the photoswitching property of Dronpa. Reversible photoswitching was lost in cells expressing the Dronpa-C62S upon repetitive irradiation compared to the native protein. Structural and mutational analyses reveal the chemical basis for the functional properties of photoswitchable fluorescent proteins and provide the basis for subsequent coherent engineering of this subfamily of Dronpa homologs. PMID- 17276393 TI - Human cellular prion protein hPrPC is sorted to the apical membrane of epithelial cells. AB - Propagation of the scrapie isoform of the prion protein (PrP(Sc)) depends on the expression of endogenous cellular prion (PrP(C)). During oral infection, PrP(Sc) propagates, by conversion of the PrP(C) to PrP(Sc), from the gastrointestinal tract to the nervous system. Intestinal epithelium could serve as the primary site for PrP(C) conversion. To investigate PrP(C) sorting in epithelia cells, we have generated both a green fluorescent protein (EGFP) or hemagglutinin (HA) tagged human PrP(C) (hPrP(C)). Combined molecular, biochemical, and single living polarized cell imaging characterizations suggest that hPrP(C) is selectively targeted to the apical side of Madin-Darby canine kidney (MDCKII) and of intestinal epithelia (Caco2) cells. PMID- 17276394 TI - Disruption of the intracellular Ca2+ homeostasis in the cardiac excitation contraction coupling is a crucial mechanism of arrhythmic toxicity in aconitine induced cardiomyocytes. AB - Aconitine is an effective ingredient in Aconite tuber, an important traditional Chinese medicine. Aconitine is also known to be a highly toxic diterpenoid alkaloid with arrhythmogenic effects. In the present study, we have characterized the properties of arrhythmic cytotoxicity and explored the possible mechanisms of aconitine-induced cardiomyocytes. Results show that aconitine induces significant abnormity in the spontaneous beating rate, amplitude of spontaneous oscillations and the relative intracellular Ca(2+) concentration. Also, mRNA transcription levels and protein expressions of SR Ca(2+) release channel RyR(2) and sarcolemmal NCX were elevated in aconitine-induced cardiomyocytes. However, co treatment with ruthenium red (RR), a RyR channel inhibitor, could reverse the aconitine-induced abnormity in intracellular Ca(2+) signals. These results demonstrate that disruption of intracellular Ca(2+) homeostasis in the cardiac excitation-contraction coupling (EC coupling) is a crucial mechanism of arrhythmic cytotoxicity in aconitine-induced cardiomyocytes. Moreover, certain inhibitors appear to play an important role in the detoxification of aconitine induced Ca(2+)-dependent arrhythmias. PMID- 17276396 TI - Conditional RNA interference achieved by Oct-1 POU/rtTA fusion protein activator and a modified TRE-mouse U6 promoter. AB - RNA interference (RNAi) is a powerful technique and is widely used to down regulate expression of specific genes in cultured cells and in vivo. In this paper, we report our development of a new tetracycline-inducible RNAi expression using a modified TRE-mouse U6 promoter in which the distal sequence element (DSE) was replaced by the tetracycline-responsive element (TRE). The modified TRE-mouse U6 promoter can be activated by a Tet-on version tetracycline-regulated artificial activator rTetOct which was constructed by fusing the rtTA DNA binding domain with the Oct-1 POU activation domain. This rTetOct/TRE-U6 system was successfully applied to conditionally and reversibly down-regulate the expression of endogenous p53 gene in MCF7 cells, and the expression of beta-defensin gene (mBin1b) either transiently expressed in COS7 cells or stably expressed in CHO cells. PMID- 17276395 TI - A p53-type response element in the GDF15 promoter confers high specificity for p53 activation. AB - GDF15 is a transcriptional target gene for p53 and its family members, p63 and p73. Its promoter region contains two p53-type response elements, RE1 and RE2, and RE2 confers p53-specific transactivation. RE2 contains several mismatches from the canonical p53 response element (RRRCWWGYYY). Two mismatches in the RRR span and T base of the RE2 core sequence in the most 3' quarter-site are critical for inhibiting the binding affinity to p63 and p73 and corresponding promoter activity. Our results strongly suggest that differential DNA-binding affinities between p53 family member proteins act, at least in part, to confer specific target gene activation. PMID- 17276397 TI - Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line. AB - p53 is a key modulator of a variety of cellular stresses. In human neuroblastomas, p53 is rarely mutated and aberrantly expressed in cytoplasm. In this study, we have identified a novel p53 mutant lacking its COOH-terminal region in neuroblastoma SK-N-AS cells. p53 accumulated in response to cisplatin (CDDP) and thereby promoting apoptosis in neuroblastoma SH-SY5Y cells bearing wild-type p53, whereas SK-N-AS cells did not undergo apoptosis. We found another p53 (p53DeltaC) lacking a part of oligomerization domain and nuclear localization signals in SK-N-AS cells. p53DeltaC was expressed largely in cytoplasm and lost the transactivation function. Furthermore, a 3'-part of the p53 locus was homozygously deleted in SK-N-AS cells. Thus, our present findings suggest that p53 plays an important role in the DNA-damage response in certain neuroblastoma cells and it seems to be important to search for p53 mutations outside DNA binding domain. PMID- 17276398 TI - Differentiation of a hepatic phenotype after heterotropic transplantation of heart, kidney, brain, and skin tissues into liver in F344 rats. AB - While organ-specific stem cells with roles in tissue injury repair have been documented, their pathogenic significance in diseases and the factors potentially responsible for their activation remain largely unclear. In the present study, heart, kidney, brain, and skin samples from F344 transgenic rats carrying the GFP gene were transplanted into normal F344 rat liver one day after an intraperitoneal injection (i.p.) of carbon tetrachloride (CCl(4)) to test their differentiation capacity. The transplantation was carried out by female donors to male recipients, and vice versa. One week after transplantation, GFP antigen positive cells with phenotypic characteristics of hepatocytes were noted. After two weeks, their extent increased, and at 4 weeks, large areas of strongly GFP stained cells developed. All recipient livers had GFP antigen-positive hepatocyte cells. PCR analysis coupled with laser capture micro-dissection (LCM) revealed those cells to contain GFP DNA. Thus, our results indicate that tissue stem cells have multipotential ability, differentiating into hepatocytes when transplanted into an injured liver. PMID- 17276399 TI - Cross-talk between Smad and p38 MAPK signalling in transforming growth factor beta signal transduction in human glioblastoma cells. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine involved in the regulation of cell proliferation, differentiation, and survival. Malignant tumour cells often do not respond to TGF-beta by growth inhibition, but retain responsiveness to cytokine in regulating extracellular matrix deposition, cell adhesion, and migration. We demonstrated that TGF-beta1 does not affect viability or proliferation of human glioblastoma T98G, but increases transcriptional responses exemplified by induction of MMP-9 expression. TGF-beta receptors were functional in T98G glioblastoma cells leading to SMAD3/SMAD4 nuclear translocation and activation of SMAD-dependent promoter. In parallel, a selective activation of p38 MAPK, and phosphorylation of its substrates: ATF2 and c-Jun proteins were followed by a transient activation of AP-1 transcription factor. Surprisingly, an inhibition of p38 MAPK with a specific inhibitor, SB202190, abolished TGF-inducible activation of Smad-dependent promoter and decreased Smad2 phosphorylation. It suggests an unexpected interaction between Smad and p38 MAPK pathways in TGF-beta1-induced signalling. PMID- 17276401 TI - The death domain of IRAK-1: an oligomerization domain mediating interactions with MyD88, Tollip, IRAK-1, and IRAK-4. AB - Ligand binding in the Toll-like/interleukin-1 receptor family results in the recruitment of an intracellular signaling complex. IRAK-1, which is centrally involved in this complex, is able to homo-oligomerize and to bind to Tollip and the adapters MyD88 and IRAK-4. The interactions of IRAK-1 with MyD88 or Tollip are mediated by the N-terminal part of IRAK-1, containing the death domain with the highly conserved threonine at position 66 (T66). Mutation of this amino acid into alanine or aspartic acid stabilized binding to MyD88, Tollip, and IRAK-4, allowing the definitive experimental proof, that all these interactions are mediated by the death domain of IRAK-1. Homo-oligomerization of IRAK-1, which is mediated by the death domain too, is not affected by mutation of T66. Finally, mutation of IRAK-1 at T66 not only allowed stable binding to the signaling adapters, but also enhanced its signaling capacity. PMID- 17276400 TI - Novel cell culture device enabling three-dimensional cell growth and improved cell function. AB - A better understanding of cell biology and cell-cell interactions requires three dimensional (3-D) culture systems that more closely represent the natural structure and function of tissues in vivo. Here, we present a novel device that provides an environment for routine 3-D cell growth in vitro. We have developed a thin membrane of polystyrene scaffold with a well defined and uniform porous architecture and have adapted this material for cell culture applications. We have exemplified the application of this technology by growing HepG2 liver cells on 2- and 3-D substrates. The performance of HepG2 cells grown on scaffolds was significantly enhanced compared to functional activity of cells grown on 2-D plastic. The incorporation of thin membranes of porous polystyrene to create a novel device has been successfully demonstrated as a new 3-D cell growth technology for routine use in cell culture. PMID- 17276402 TI - AMP-activated protein kinase mediates VEGF-stimulated endothelial NO production. AB - Vascular endothelial growth factor (VEGF) is an important regulator of endothelial cell function. VEGF stimulates NO production, proposed to be a result of phosphorylation and activation of endothelial NO synthase (eNOS) at Ser1177. Phosphorylation of eNOS at this site also occurs after activation of AMP activated protein kinase (AMPK) in cultured endothelial cells. We therefore determined whether AMPK mediates VEGF-stimulated NO synthesis in endothelial cells. VEGF caused a rapid, dose-dependent stimulation of AMPK activity, with a concomitant increase in phosphorylation of eNOS at Ser1177. Infection of endothelial cells with an adenovirus expressing a dominant negative mutant AMPK partially inhibited both VEGF-stimulated eNOS Ser1177 phosphorylation and NO production. VEGF-stimulated AMPK activity was completely inhibited by the Ca(2+)/calmodulin-dependent protein kinase kinase inhibitor, STO-609. Stimulation of AMPK via Ca(2+)/calmodulin-dependent protein kinase kinase represents a novel signalling mechanism utilised by VEGF in endothelial cells that contributes to eNOS phosphorylation and NO production. PMID- 17276404 TI - Differential activation of CREB by Akt1 and Akt2. AB - Members of Akt family are highly conserved protein kinase and yet, they show clearly distinct in vivo functions. Here, we have examined the abilities of Akt1 and Akt2 to activate CREB. We found that, in contrast to Akt1 that induces CREB phosphorylation at Ser-133 and CREB target gene expression, Akt2 was unable to induce CREB phosphorylation at Ser-133 in vivo and CREB target gene expression. This difference is specific to CREB as both Akt1 and Akt2 similarly inhibits FoxO1 mediated gene expression. We further showed that the regulatory domain of Akt plays a critical role to confer Akt substrate specificity as substitution of regulatory domain of Akt1 with that of Akt2 abolished the ability of Akt1 to activate CREB. We suggest that the regulatory domain of Akts contributes to the functional difference between Akt1 and Akt2. PMID- 17276403 TI - 3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells. AB - Cytochrome CYP1A (CYP1A) enzymes catalyze bioactivation of 3-methylcholanthrene (MC) to genotoxic metabolites. Here, we tested the hypothesis that CYP1A2 catalyzes formation of MC-DNA adducts that are preferentially formed in the promoter region of CYP1A1, resulting in modulation of CYP1A1 gene expression. MC bound covalently to plasmid DNA (50 micro g) containing human CYP1A1 promoter (pGL3-1A1), when incubated with wild-type (WT) liver microsomes (2 mg) and NAPPH 37 degrees C for 2h, giving rise to 9 adducts, as determined by (32)P postlabeling. Eighty percent of adducts was located in the promoter region. Transient transfection of the adducted plasmids into rat hepatoma (H4IIE) cells for 16h, followed by MC (1 micro M) treatment for 24h inhibited reporter (luciferase) gene expression by 75%, compared to unadducted controls. Our results suggest that CYP1A2 plays a key role in sequence-specific MC-DNA adduct formation in the CYP1A1 promoter region, leading to attenuation of CYP1A1 gene expression. PMID- 17276405 TI - Synaptic neurotransmission protein UNC-13 affects RNA interference in neurons. AB - Caenorhabditis elegans UNC-13 is an integral component of the synaptic vesicle cycle, functioning in the priming step. A recent yeast two-hybrid screen against UNC-13 identified three interacting proteins that are thought to function in pathways other than neurotransmitter release. One such protein, ERI-1, negatively regulates exogenous RNA interference in the nervous system and other tissues. This study investigates a role for UNC-13 in RNAi through analysis of RNAi penetrance in unc-13 and eri-1 mutant strains. Feeding these strains double stranded RNA corresponding to a neuronally expressed GFP reporter resulted in a significant reduction of GFP in double mutants compared to GFP expression in eri 1 mutants, indicating that UNC-13 functions in conjunction with ERI-1 in RNAi. There is no evidence for altered neurotransmission in eri-1 mutants. PMID- 17276406 TI - The CDK5 activator, p39, binds specifically to myosin essential light chain. AB - Cyclin-dependent kinase 5 (Cdk5) has been shown to regulate adhesion and migration of lens and corneal epithelial cells. To explore protein-protein interactions that may mediate these functions, we performed yeast two-hybrid screening on an embryonic rat lens library using Cdk5 and its regulators, p35 and p39 as baits. This screen identified an interaction between p39 and non-muscle myosin essential light chain (MLC(17)). GST pull-down experiments demonstrated that p39 binds directly to MLC(17) through a strong binding site in the N terminal 109 amino acids of p39. Immunoprecipitation of proteins from Cos1 cells co-transfected with GFP-MLC(17) and HA-p39 confirmed that these proteins interact intracellularly. Immunofluorescence microscopy of co-transfected lens epithelial cells showed that GFP-MLC(17) and HA-p39 co-localize along cytoskeletal fibrils. Moreover, endogenous rat lens p39 co-immunoprecipitated with MLC(17) and myosin heavy chain II (MHC II), demonstrating that the interaction is physiological and serves to link p39 to the cytoskeleton. PMID- 17276407 TI - Contribution of reactivated RUNX3 to inhibition of gastric cancer cell growth following suberoylanilide hydroxamic acid (vorinostat) treatment. AB - Vorinostat (suberoylanilide hydroxamic acid, SAHA) represents a new class of highly potent histone deacetylase (HDAC) inhibitors that cause growth arrest, differentiation, and apoptosis of many tumor types in vitro and in vivo. RUNX3, a gastric tumor suppressor, is epigenetically silenced in gastric cancer cells. This study investigates the role of RUNX3 in vorinostat-induced suppression of gastric cancer cell growth. RUNX3 was up-regulated by vorinostat in gastric cancer cell lines not expressing RUNX3. In terms of cell viability, the mean IC(50) of vorinostat in RUNX3-negative cells was significantly lower than that seen in RUNX3-positive cells, indicating that the former are more sensitive to vorinostat in terms of growth arrest than are RUNX3-positive lines. The mechanism underlying this difference was found to be reactivation of RUNX3 expression by vorinostat and concomitant increase in acetylated histone H3 in the promoter region of RUNX3. Using three RUNX3-negative cell lines, we determined the contribution of RUNX3 reactivation to growth inhibition and induction of apoptosis following treatment of cells with vorinostat and found that up regulated RUNX3 was significantly responsible for tumor suppressive activities. PMID- 17276408 TI - Calcium channel antagonists: clinical uses--past, present and future. AB - The calcium channel antagonists are a mature group of drugs directed at cardiovascular diseases including hypertension, angina, peripheral vascular disorders and some arrhythmic conditions. Their sites and mechanisms of actions have been well explored over the past two decades and their interactions at the alpha(1) subunit of L-type channels (Ca(V)1.1-1.4) have made them valuable molecular tools for channel classification and localization. With the realization that other members of the voltage-gated calcium channel family exist--Ca(V)2.1 2.3 and Ca(V)3.1-3.3--considerable effort has been directed to drug discovery at these channel types where therapeutic prospects exist for a variety of disorders including pain, epilepsy, affective disorders, neurodegenerative disorders, etc. In contrast to the situation with the L-type channel antagonists success in developing small molecule antagonists of therapeutic utility for these other channel types has thus far been lacking. The reasons for this are explored and potential new directions are indicated including male fertility, bone growth, immune disorders, cancer and schistosomiasis. PMID- 17276409 TI - Structurally novel histamine H3 receptor antagonists GSK207040 and GSK334429 improve scopolamine-induced memory impairment and capsaicin-induced secondary allodynia in rats. AB - GSK207040 (5-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl 2-pyrazinecarboxamide) and GSK334429 (1-(1-methylethyl)-4-({1-[6 (trifluoromethyl)-3-pyridinyl]-4-piperidinyl}carbonyl)hexahydro-1H-1,4-diazepine) are novel and selective non-imidazole histamine H(3) receptor antagonists from distinct chemical series with high affinity for human (pK(i)=9.67+/-0.06 and 9.49+/-0.09, respectively) and rat (pK(i)=9.08+/-0.16 and 9.12+/-0.14, respectively) H(3) receptors expressed in cerebral cortex. At the human recombinant H(3) receptor, GSK207040 and GSK334429 were potent functional antagonists (pA(2)=9.26+/-0.04 and 8.84+/-0.04, respectively versus H(3) agonist induced changes in cAMP) and exhibited inverse agonist properties (pIC(50)=9.20+/ 0.36 and 8.59+/-0.04 versus basal GTPgammaS binding). Following oral administration, GSK207040 and GSK334429 potently inhibited cortical ex vivo [(3)H]-R-alpha-methylhistamine binding (ED(50)=0.03 and 0.35 mg/kg, respectively). Functional antagonism of central H(3) receptors was demonstrated by blockade of R-alpha-methylhistamine-induced dipsogenia in rats (ID(50)=0.02 and 0.11 mg/kg p.o. for GSK207040 and GSK334429, respectively). In more pathophysiologically relevant pharmacodynamic models, GSK207040 (0.1, 0.3, 1 and 3mg/kg p.o.) and GSK334429 (0.3, 1 and 3mg/kg p.o.) significantly reversed amnesia induced by the cholinergic antagonist scopolamine in a passive avoidance paradigm. In addition, GSK207040 (0.1, 0.3 and 1mg/kg p.o.) and GSK334429 (3 and 10mg/kg p.o.) significantly reversed capsaicin-induced reductions in paw withdrawal threshold, suggesting for the first time that blockade of H(3) receptors may be able to reduce tactile allodynia. Novel H(3) receptor antagonists such as GSK207040 and GSK334429 may therefore have therapeutic potential not only in dementia but also in neuropathic pain. PMID- 17276410 TI - Isoliquiritigenin inhibits IkappaB kinase activity and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human endothelial cells. AB - Isoliquiritigenin (ILTG) is a flavonoid with chalcone structure (4,2',4' trihydroxychalcone), an active component present in plants like Glycyrrhiza and Dalbergia which showed various biological activities including anti-inflammatory, anti-carcinogenic and antihistamic. As very little is known in regard to the underlying mechanism involved in explaining the various activities of the compound, we carried out a detailed study on the effect of ILTG on the expression of cell adhesion molecules on human primary endothelial cells. We demonstrate here that ILTG inhibits TNF-alpha induced adhesion of neutrophils to endothelial monolayer by blocking the expression of ICAM-1, VCAM-1 and E-selectin. Since NF kappaB is a major transcription factor involved in the transcriptional regulation of cell adhesion molecules, thus we studied the status of NF-kappaB activation in ILTG treated endothelial cells. We demonstrate that ILTG inhibits the translocation and activation of nuclear factor-kappaB (NF-kappaB) by blocking the phosphorylation and subsequent degradation of IkappaBalpha. As oxidative stress is also known to regulate the activation of NF-kappaB to modulate TNF-alpha signaling cascade, we tested the effect of ILTG on reactive oxygen species (ROS). We found that it inhibits TNF-alpha induced ROS production in endothelial cells. These results have important implications for using ILTG or its derivatives towards the development of effective anti-inflammatory molecules. PMID- 17276411 TI - Histone deacetylase inhibitor Trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines. AB - DNA methylation and chromatin structure are two modes of epigenetic control of genome function. Although it is now well established that chromatin silencing could lead to DNA methylation, the relation between chromatin activation and DNA demethylation is unclear. It was generally believed that expression of methylated genes could only be restored by demethylating agents, such as 5-aza-deoxycytidine (5-azaCdR), and that inhibition of histone deacetylation by Trichostatin A (TSA) only activates transcription of unmethylated genes. In this report, we show that increase of histone acetylation by TSA was associated with a significant decrease in global methylation. This global demethylation occurs even when DNA replication is blocked by hydroxyurea, supporting a replication-independent-mechanism of demethylation. TSA also induces histone acetylation, demethylation and expression of the methylated E-CADHERIN and RARbeta2 genes. However, the genome-wide demethylation induced by TSA does not affect all methylated tumor suppressor genes equally suggesting that induction of acetylation and demethylation by TSA shows some gene selectivity. Taken together, our data provide evidence for a reversible crosstalk between histone acetylation and DNA demethylation, which has significant implications on the use of HDAC inhibitors as therapeutic agents. PMID- 17276412 TI - Molecular aspects of the histamine H3 receptor. AB - The cloning of the histamine H(3) receptor (H(3)R) cDNA in 1999 by Lovenberg et al. [10] allowed detailed studies of its molecular aspects and indicated that the H(3)R can activate several signal transduction pathways including G(i/o) dependent inhibition of adenylyl cyclase, activation of phospholipase A(2), Akt and the mitogen activated kinase as well as the inhibition of the Na(+)/H(+) exchanger and inhibition of K(+)-induced Ca(2+) mobilization. Moreover, cloning of the H(3)R has led to the discovery several H(3)R isoforms generated through alternative splicing of the H(3)R mRNA. The H(3)R has gained the interest of many pharmaceutical companies as a potential drug target for the treatment of various important disorders like obesity, myocardial ischemia, migraine, inflammatory diseases and several CNS disorders like Alzheimer's disease, attention-deficit hyperactivity disorder and schizophrenia. In this paper, we review various molecular aspects of the hH(3)R including its signal transduction, dimerization and the occurrence of different H(3)R isoforms. PMID- 17276413 TI - Detecting pop-out targets in contexts of varying homogeneity: investigating homogeneity coding with event-related brain potentials (ERPs). AB - Searching for a target among many distracting context elements might be an easy or a demanding task. Duncan and Humphreys (Duncan, J., Humphreys, G.W., 1989. Visual search and stimulus similarity. Psychol. Rev. 96, 433-458) showed that not only the target itself plays a role in the difficulty of target detection. Similarity among context elements and dissimilarity of target and context are two main factors also affecting search efficiency. Moreover, many studies have shown that search becomes particularly efficient with large set sizes and perfectly homogeneous context elements, presumably due to grouping processes involved in target-context segmentation. Especially N2p amplitude has been found to be modulated by the number of context elements and their homogeneity. The aim of the present study was to investigate the influence of context elements of different heterogeneities on search performance using event-related brain potentials (ERPs). Results showed that contexts with perfectly homogeneous elements were indeed special: they were most efficient in visual search and elicited a large N2p differential amplitude effect. Increasing context heterogeneity led to a decrease in search performance and a reduction in N2p differential amplitude. Reducing the number of context elements led to a marked performance decrease for random heterogeneous contexts but not for grouped heterogeneous contexts. Behavioral and N2p results delivered evidence (a) in favor of specific processing modes operating on different spatial scales (b) for the existence of homogeneity coding postulated by Duncan and Humphreys. PMID- 17276415 TI - Coregulation of light neurofilament mRNA by poly(A)-binding protein and aldolase C: implications for neurodegeneration. AB - The multifunctional proteins aldolase C and poly (A)-binding protein (PABP) undergo competitive interactions in cells coexpressing aldolase C and NF-L. A specific in vivo interaction between aldolase C and NF-L mRNA had been localized to a 68 nt segment of the transcript spanning the translation termination signal. It is shown here that the poly (A)-binding protein (PABP) binds the body of the NF-L transcript and increases its levels of expression when an excess of PABP is transiently provided in trans. Immunoprecipitation of PABP-associated ribonucleoprotein complexes of human spinal cord pulls down the dimeric form of aldolase C suggesting that their co-regulation of NF-L expression could be linked to the oligomerization status of aldolase C. An ex vivo model of mRNA decay has assessed mechanisms whereby aldolase C and PABP control NF-L expression. This model shows that aldolase C is a zinc-activated ribonuclease that cleaves the transcript at sites closed to the end-terminal structures. Immunological and biochemical depletion of endogenous PABP increases the instability of the transcript suggesting that PABP shields the NF-L mRNA from aldolase attack. An in vitro model shows that a mutant NF-L 68, in which the 45 nt of proximal 3'-UTR is replaced with unrelated sequence, is not degraded by aldolase C. Taken together, the findings might have important consequences for understanding causal mechanisms underlying neurodegeneration. PMID- 17276414 TI - Macromolecules involved in production and metabolism of beta-amyloid at the brain barriers. AB - One of the notable features of Alzheimer's disease (AD) is the overabundance of beta-amyloid peptides in brain fluids, leading to the formation and deposition of insoluble amyloid plaques. Previous work in this lab demonstrates that the normal choroid plexus, a primary component of the blood-cerebrospinal fluid barrier, has the capacity to remove beta-amyloid from the cerebrospinal fluid, potentially preventing the formation of beta-amyloid plaques. The purpose of this work was to determine whether the choroid plexus and/or the brain capillaries, a primary component of the blood-brain barrier, possessed the capacity to produce or degrade beta-amyloid peptides. Using quantitative real-time RT-PCR, immunodetection and enzyme activity assays, we demonstrated the presence in brain barriers of several key enzymes involved in beta-amyloid production, namely, amyloid precursor protein and beta-secretase, and in beta-amyloid metabolism and alternate processing, such as insulin degrading enzyme, endothelin-converting enzyme-1, neprilysin and alpha-secretase. Furthermore, beta-amyloid presence, in the absence of its application in culture media, was detected in an immortalized choroidal epithelial cell line, known as Z310 cells. The ability of the choroid plexus to produce and degrade beta-amyloid, in addition to its transport function, suggests a vital role of this tissue in maintaining beta-amyloid homeostasis. Disruption of this homeostasis due to aging, injury or toxicant exposure may contribute to accumulation of beta-amyloid peptides in the brain fluids, leading to AD. PMID- 17276418 TI - Sex steroid hormones and sexual dimorphism of chemosensory structures in a terrestrial salamander (Plethodon shermani). AB - The volume of the vomeronasal organ (VNO) in the terrestrial salamander Plethodon shermani was approximately 1.7 times larger in adult males compared to adult females, even though male body size was, on average, slightly smaller than female body size. VNO cell density, however, was the same in adult males and females. The sex difference in VNO volume was found in sexually immature animals as well, indicating that the increase of plasma androgens that occurs at sexual maturity does not produce the sex difference in VNO volume. There was no difference in VNO volume between reproductive and non reproductive adult females, despite differences in plasma estradiol (E2) levels. The volumes of the main olfactory epithelium and muscles regulating diameter of the external nares were similar between males and females, indicating that the VNO per se, and not other aspects of the nasal cavity, was sexually dimorphic. To conclude, the sex difference in VNO volume appears to be a permanent sex difference that develops before sexual maturity. Future studies will examine the functional consequences of this structural sexual dimorphism in a peripheral sensory organ, the VNO. PMID- 17276416 TI - GABAergic circuits and the stress hyporesponsive period in the rat: ontogeny of glutamic acid decarboxylase (GAD) 67 mRNA expression in limbic-hypothalamic stress pathways. AB - Development of the hypothalamo-pituitary-adrenocortical (HPA) axis is marked by a diminution in stress responsiveness early in the postnatal period (days 4-14 in the rat). This 'stress hyporesponsive period' (SHRP) is thought to be at least in part centrally mediated. To investigate central mechanisms underlying the SHRP, this study assessed expression of glutamic acid decarboxylase (GAD) 67 in key stress-regulatory regions in the forebrain following acute stress with or without prior maternal deprivation. This isoform of GAD is known to be induced by stress in the adult and is believed to be a major contributor to production of the inhibitory neurotransmitter GABA under stimulated conditions. Expression of GAD67 mRNA was increased in the hippocampus, central amygdala and dorsomedial hypothalamus in pups tested early in the SHRP (day 6) or after its conclusion (day 18). In contrast, restraint caused a down-regulation of GAD67 mRNA in these structures when tested later in the SHRP (day 12). GAD67 mRNA expression was not affected by prior maternal deprivation in these regions. Reduced GABA production in the hippocampus (interneurons) is consistent with enhanced HPA axis inhibition, whereas reduced amygdalar expression predicts impaired stress excitation. Expression of GAD67 mRNA in the bed nucleus of the stria terminalis (BST) was minimally affected by acute restraint or maternal deprivation during the SHRP. However, older animals showed down-regulation of basal expression following maternal deprivation and substantial GAD67 mRNA up-regulation in both deprived and non-deprived groups following acute restraint. In contrast, non responsiveness of the BST during the SHRP suggests either that BST GABA circuits are not actively engaged by stressors during this period or that circuits regulating BST GAD67 production are not yet in place. Overall, the data implicate forebrain GABA circuits in inhibition of HPA axis activity during the SHRP. PMID- 17276419 TI - Auditory nerve input is not an absolute requirement for the expression, distribution and calcium permeability of AMPA receptors in the adult rat ventral cochlear nucleus. AB - In order to understand whether glutamatergic excitatory presynaptic input is an absolute requirement for the adult regulation of postsynaptic glutamate receptors we analyzed if a period of 11 days of excitatory deprivation affects the expression, distribution and Ca(2+) permeability of AMPA receptor subunits in the ventral cochlear nucleus of the rat. Bilateral cochlear ablations were performed in 30-day-old rats. After 11 days of survival, immunohistochemistry for GluR1, GluR2/3 and GluR4 AMPA receptor subunits showed no changes in the normal pattern of distribution, with GluR2/3 and GluR4 immunoreactivity predominating, and little GluR1. No changes in the amount of these AMPA receptor subunits were found between normal and cochleotomized rats in Western blots. AMPA receptors lacking the GluR2 subunit are Ca(2+) permeable. Kainate-induced Co(2+) uptake histochemistry, which labels AMPA Ca(2+) permeable receptors, demonstrated no changes in somatic labeling intensity for Co(2+), 11 days after cochleotomy. Therefore, our data indicate that excitatory input is not an absolute requirement to maintain AMPA receptor subunit expression, distribution and functional properties such as Ca(2+) permeability in VCN neurons. Nevertheless, subtle changes in AMPA receptors through regulatory post-transductional mechanisms cannot be ruled out. PMID- 17276417 TI - The role of 5-HT(7) receptors in the control of seizures. AB - Serotonin exerts its effects via at least 14 different receptor subtypes, but the role of only a few of them has been studied in relation to the control of seizures. A negative role of 5-HT(7) receptors has recently been proposed. To evaluate further in unstressed and stressed animals the possible role of this receptor subtype in the control of brain excitability, we treated mice with antagonists and agonists of these receptors prior to exposure to swim stress and the intravenous infusion of picrotoxin, a non-competitive GABA(A) receptor antagonist. In accordance with the previous studies, swim stress increased the doses of picrotoxin producing two convulsant signs (running/bouncing clonus, tonic hindlimb extension) and death, i.e., swim stress increased the seizure threshold for picrotoxin. SB-269970 (10-30 mg/kg ip), a selective antagonist of 5 HT(7) receptors, and ritanserin (1 mg/kg ip), a nonselective 5-HT (2/7) antagonist, failed to affect, while 5-carboxamidotryptamine (5-CT), a potent 5-HT (1/7) receptor agonist, increased in unstressed and swim-stressed mice the doses of picrotoxin producing convulsions and death. The anticonvulsant effect obtained with 5-CT 0.5 mg/kg was not greater than that obtained with 0.1 mg/kg. The 5-CT (0.1 mg/kg ip)-induced increase of the seizure threshold for picrotoxin in stressed mice was abolished with SB-269970 (10 mg/kg), but not with WAY-100635 (0.3 mg/kg), a selective antagonist of 5-HT(1A) receptors, suggesting that the anticonvulsant effect of 5-CT against convulsions produced by picrotoxin was achieved via 5-HT(7) receptors. The results suggest a positive role of 5-HT(7) receptors in the control of seizures. PMID- 17276420 TI - The effects of reversible inactivation of postero-temporal visual cortex on neuronal activities in cat's area 17. AB - 'Spontaneous' and visually evoked action potentials were recorded from single neurons in cytoarchitectonic area 17 (striate cortex, area V1) of anaesthetized and immobilized cats, prior to, during and after brief reversible inactivation of the ipsilateral postero-temporal visual (PTV) cortex (presumed homologue of primate inferotemporal cortex). Inactivation of PTV cortex resulted: 1) in significant changes in the response magnitude (mostly a reduction) to optimal and/or sub-optimal visual stimuli in over 55% of area 17 cells and 2) significant changes (usually a reduction) in the 'spontaneous' (background) activity of about two-thirds of the cells in which inactivation of PTV cortex significantly affected the magnitude of responses to optimal stimuli. In over 85% of the significantly affected area 17 cells, rewarming PTV cortex to normal temperature (36 degrees C) resulted in the recovery of both the magnitude of responses and the background activity to levels not significantly different from pre inactivation levels. Irrespective of the significance of changes in the magnitude of responses, in a substantial proportion of area 17 cells, inactivation of PTV cortex resulted in changes in some receptive field characteristics. Thus, there were substantial (20% or more) changes in orientation tuning widths (in over a quarter of the sample) and/or direction selectivity indices (in about a third of the sample). Thus, the feedback signals originating from PTV cortex, like signals originating from some other 'higher-order' visual cortical areas exert a clear modulatory influence on the responsiveness, background activity and some receptive field properties of neurons in the ipsilateral area 17. PMID- 17276421 TI - Involvement of forebrain in parabrachial neuronal activation induced by aversively conditioned taste stimuli in the rat. AB - We previously have shown that forebrain inputs increase responses of amiloride sensitive NaCl-best neurons to the conditioned stimulus (CS) in the rat parabrachial nucleus (PBN) after the establishment of conditioned taste aversion (CTA) to NaCl. In the present study, we examined the effects of aversively conditioned NaCl taste stimulation on Fos-like immunoreactivity (FLI) in the PBN using awake intact and decerebrate rats. In Experiment 1, the CTA-trained and sham-conditioned control rats were intraorally infused with 0.1 M NaCl or 0.1 M NaCl mixed with 10(-4) M amiloride, a sodium-channel blocker. Significantly more NaCl-stimulated FLI was observed in the central medial (cms) and external lateral subnuclei (els) of PBN in the CTA-trained group than in the control group. In both groups, amiloride markedly reduced NaCl-stimulated FLI in the cms but not in the els. In Experiment 2, we found that after decerebration, there was no significant difference in FLI between the CTA-trained and sham-conditioned groups. These results suggest that (1) amirolide-sensitive taste information of NaCl projects mainly to the cms; (2) sensory information of aversive taste stimuli is likely to be represented in the els; and (3) forebrain inputs are required for elevated FLI in the PBN after CTA. PMID- 17276422 TI - Region-specific mechanisms for testosterone-induced Fos in hamster brain. AB - Hamsters self-administer androgens. Previously, we determined that testosterone (T) activates select steroid- and opiate-sensitive brain regions. Is T-stimulated neuronal activation androgenic? Thirty-five castrated males with physiologic T replacement (n=7/group) were pre-treated with the androgen antagonist flutamide (15 mg/kg sc) or ethanol (0.25 ml) and infused into the lateral ventricle (ICV) for 4 h with 40 microg T (TF and TE, respectively) or 40 microl vehicle (VF and VE). To determine if androgens and opiates activate overlapping brain areas, 7 additional males received 20 mug morphine sulfate ICV following ethanol injection (ME). Immediately after ICV infusion, animals were perfused. Sixty-micrometer coronal brain slices were stained for Fos. Fos-positive neurons were counted in a 0.3-mm(2) area from 5 regions previously shown to express T-induced Fos: the posteromedial bed nucleus of the stria terminalis (BSTPM), posteromedial amygdala (MeP), lateral habenula (LHb), ventral tegmental area, and lateral pontine nucleus. T induced Fos in all areas reported previously (TE vs. VE, p<0.05), except LHb (p>0.05). Morphine induced Fos in all 5 brain regions (ME vs. VE, p<0.05), indicating that androgens and opiates activate overlapping brain regions. Flutamide alone did not induce Fos (VF vs. VE, p>0.05). Moreover, flutamide treatment blocked T-induced Fos expression only in the steroid sensitive BSTPM, suggesting that androgens mediate neuronal activation in this area (mean+/-SEM: TF: 68.4+/-13.2 vs. TE: 137.9+/-17.6, p<0.05). The absence of flutamide effects on T-induced Fos in the steroid-sensitive MeP (TE: 210.6+/-50.0 vs. TF: 215.3+/-28.2, p>0.05) suggests that distinct mechanisms activate Fos in individual androgen-responsive nuclei. PMID- 17276424 TI - Assessing the effects of surfactants on the physical properties of liposome membranes. AB - Knowledge of the partition process of environmentally significant molecules between biological membranes and their surroundings is of vital importance to explain their activity and toxicity, as well as phenomena like absorption, distribution and metabolism. In this research effort, we have studied membrane interactions of three surfactants: t-octylphenoxypolyethoxyethanol (Triton X 100), cetyltrimethylammonium chloride (CTAC) and dodecylbenzene sulphonate (SDBS). Unilamellar liposomes (LUVs) of egg yolk phosphatidylcholine (EPC) were used as membrane models. The partition coefficient, a fundamental parameter in assessing the behaviour of xenobiotic compounds, was determined for SDBS and Triton X-100 by derivative spectrophotometry and fluorescence quenching. The effect of these surfactants upon the physico-chemical characteristics (fluidity, diameter and surface charge) of the liposome membrane was also determined. Results show that all the three surfactants cause an increase in fluidity of the liposome membrane, although for low surfactant concentrations uncharacteristic membrane rigidity was observed, probably due to a change in lipid packing density. PMID- 17276423 TI - Lack of NF-kappaB1 (p105/p50) attenuates unloading-induced downregulation of PPARalpha and PPARalpha-regulated gene expression in rodent heart. AB - OBJECTIVE: Unloading of the rodent heart activates the fetal gene program, decreases peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARalpha-regulated gene expression (MCAD), and induces cardiomyocyte atrophy. NF kappaB regulates the fetal gene program and PPARalpha-regulated gene expression during cardiac hypertrophy and induces atrophy in skeletal muscle. Our objective was to test the hypothesis that NF-kappaB is the regulator for activation of the fetal gene program, for downregulation of PPARalpha and PPARalpha-regulated gene expression, and for cardiomyocyte atrophy in the heart subjected to mechanical unloading. METHODS: Activation of the inhibitory kappa B kinase beta (IKKbeta)/NF kappaB pathways were measured in the heterotopically transplanted rat heart using Western blotting of total and phospho-IKKbeta and using transcription factor ELISA's for the five members of the NF-kappaB family (p65 (Rel A), p105/p50, c Rel, RelB, and p100/p52). In loss of function experiments, we transplanted hearts of p105/p50 knockout mice into wildtype mice and compared changes in gene expression and cardiomyocyte size with wildtype hearts transplanted into wildtype mice. RESULTS: Total and phospho-IKKbeta levels significantly increased in the transplanted heart seven days after surgery. The activation of IKKbeta was paralleled by increased DNA binding activity of p65 and p105/p50. Mechanical unloading induced myosin heavy chain beta expression and decreased cardiomyocyte size in hearts of both wildtype and p105/p050 knockout animals. In contrast, the downregulation of PPARalpha and MCAD was significantly attenuated or prevented in the hearts of p105/p50 knockout mice. CONCLUSIONS: The IKKbeta/p65/p50 pathway is activated in the unloaded rodent heart and a likely regulator for the downregulation of PPARalpha and PPARalpha-regulated gene expression. PMID- 17276425 TI - A more flexible parametric estimation of univariate reference intervals: a new method based on the GS-distribution. AB - BACKGROUND: Reference interval estimation is an important issue in clinical laboratories. Present methods are based either on data transformation or on non parametric approaches. METHODS: We present a new technique based in a family of statistical distributions known as GS-distributions that provide a suitable model for continuous unimodal variables. We compare, both by simulation studies an on actual data, the reference intervals estimated by using non-parametric methods and data transformations suggested by the IFCC and those obtained by fitting a GS distribution. Simulated data are generated from various distributions to evaluate the accuracy of these methods. In each case, confidence intervals for the resulting reference intervals are obtained by bootstrap. RESULTS: In all the cases, the GS-distribution based method provides comparable or more accurate results than the non-parametric methods. In most cases, the proposed method produces better results than those obtained by transforming the original data. CONCLUSIONS: Our results suggest that the method for computing reference intervals based on GS-distribution is a valid alternative for the current non parametric methods. PMID- 17276426 TI - Control of sperm concentration is necessary for standardization of sperm cryopreservation in aquatic species: evidence from sperm agglutination in oysters. AB - A lack of standardization in sperm cryopreservation of aquatic organisms is one of the main reasons for inconsistency observed among various studies. In particular, there have been few attempts to standardize sperm concentration during procedural optimization. This study was intended to call attention to sperm concentration standardization through research of sperm agglutination in Pacific oysters Crassostrea gigas. Sperm agglutination after thawing is a relatively frequent phenomenon observed for various aquatic species, especially when sub-optimal cryopreservation protocols are used; however, no systematic attempts have been made to explain this phenomenon. The present study evaluated various factors affecting sperm agglutination of thawed samples from diploid and tetraploid Pacific oysters, and is the first detailed report addressing the sperm agglutination phenomenon of thawed samples from any aquatic organism. Agglutination of oyster sperm was classified into six levels with a scale ranging from 0 (homogenous suspension) to 5 (well-developed "noodles"). It was found that agglutination in thawed samples was mainly due to the lack of sufficient cryoprotectant for a specific sperm concentration. Interestingly, high levels of agglutination did not necessarily lead to low fertilization. On the contrary, some sperm cells appeared to gain protection from the formation of peripheral agglutination within 0.5-ml French straws. The exact mechanism of sperm agglutination remains unclear. However, morphological examination of cross sections of the noodles (agglutination level 5) indicated at least two forms of agglutination (formed with and without cryoprotectant) which could be used as a tool to understand the cryopreservation process within the micro-environment of the straw. Furthermore, the fact that the level of sperm agglutination was directly determined by sperm concentration, in addition to the type of cryoprotectant, cryoprotectant concentration, and cooling and thawing methods emphasized the importance of procedural standardization and systematic optimization and integration of protocols involving multiple factors. PMID- 17276427 TI - Altered poly(ADP-ribose) metabolism impairs cellular responses to genotoxic stress in a hypomorphic mutant of poly(ADP-ribose) glycohydrolase. AB - Genotoxic stress activates nuclear poly(ADP-ribose) (PAR) metabolism leading to PAR synthesis catalyzed by DNA damage activated poly(ADP-ribose) polymerases (PARPs) and rapid PAR turnover by action of nuclear poly(ADP-ribose) glycohydrolase (PARG). The involvement of PARP-1 and PARP-2 in responses to DNA damage has been well studied but the involvement of nuclear PARG is less well understood. To gain insights into the function of nuclear PARG in DNA damage responses, we have quantitatively studied PAR metabolism in cells derived from a hypomorphic mutant mouse model in which exons 2 and 3 of the PARG gene have been deleted (PARG-Delta2,3 cells), resulting in a nuclear PARG containing a catalytic domain but lacking the N-terminal region (A domain) of the protein. Following DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), we found that the activity of both PARG and PARPs in intact cells is increased in PARG-Delta2,3 cells. The increased PARG activity leads to decreased PARP-1 automodification with resulting increased PARP activity. The degree of PARG activation is greater than PARP, resulting in decreased PAR accumulation. Following MNNG treatment, PARG-Delta2,3 cells show reduced formation of XRCC1 foci, delayed H2AX phosphorylation, decreased DNA break intermediates during repair, and increased cell death. Our results show that a precise coordination of PARPs and PARG activities is important for normal cellular responses to DNA damage and that this coordination is defective in the absence of the PARG A domain. PMID- 17276428 TI - Phagocytosis and remodeling of collagen matrices. AB - The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for the integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lung fibroblast behavior in vitro in terms of collagen uptake and matrix remodeling. Therefore, in the present work, the response of human fibroblasts (IMR-90) to the structural state of collagen was studied with respect to phagocytosis in the presence and absence of inhibitors. Protein content and transcript levels for collagen I (Col-1), matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and heat shock protein 70 (HSP-70) were characterized as a function of collagen matrix concentration, structure and cell culture time to assess effects on cellular collagen matrix remodeling processes. Phagocytosis of collagen was assessed quantitatively by the uptake of collagen coated fluorescent beads incorporated into the collagen matrices. Significantly higher levels of collagen phagocytosis were observed for the cells grown on the denatured collagen versus native collagen matrices. Significant reduction in collagen phagocytosis was observed by blocking several phagocytosis pathways when the cells were grown on denatured collagen versus non-denatured collagen. Collagen phagocytosis inhibition effects were significantly greater for PDL57 IMR 90 cells versus PDL48 cells, reflecting a reduced number of collagen processing pathways available to the older cells. Transcript levels related to the deposition of new extracellular matrix proteins varied as a function of the structure of the collagen matrix presented to the cells. A four-fold increase in transcript level of Col-1 and a higher level of collagen matrix incorporation were observed for cells grown on denatured collagen versus cells grown on non denatured collagen. The data suggest that biomaterial matrices incorporating denatured collagen may promote more active remodeling toward new extracellular matrices in comparison to cells grown on non-denatured collagen. A similar effect of cellular action toward denatured (wound-related) collagen in the remodeling of tissues in vivo may have significant impact on tissue regeneration as well as the progression of collagen-related diseases. PMID- 17276429 TI - Phosphatidic acid as a regulator of matrix metalloproteinase-9 expression via the TNF-alpha signaling pathway. AB - Phosphatidic acid (PA) is implicated in pathophysiological processes associated with cellular signaling events and inflammation, which include the expressional regulation of numerous genes. Here, we show that PA stimulation increases matrix metalloproteinase-9 (MMP-9) expression in macrophages through tumor necrosis factor (TNF)-alpha signaling. We performed antibody array analysis on proteins from macrophages stimulated with PA. PA was found to induce the production of TNF alpha, but not of TNF receptor (TNFR)1 and TNFR2 in a time-dependent manner and stimulated significant, though delayed, MMP-9 expression. PA induced the phosphorylations of both ERK1/2 and p38, but not of c-jun amino-terminal kinase. Moreover, only ERK1/2 inhibition by U0126 suppressed PA-induced TNF-alpha production and MMP-9 expression. Neutralizing TNF-alpha, TNFR1 or TNFR2 antibodies significantly suppressed PA-induced MMP-9 expression, suggesting that the production of TNF-alpha in response to PA preceded the expression of MMP-9. Moreover, lipopolysaccharide-induced PA also led to TNF-alpha release and resulted in MMP-9 expression. Taken together, these observations suggest that PA may play a role in MMP-9 regulation through ERKs/TNF-alpha/TNFRs-dependent signaling pathway. PMID- 17276430 TI - Systematic screening of LNA/2'-O-methyl chimeric derivatives of a TAR RNA aptamer. AB - We synthesized and evaluated by surface plasmon resonance 64 LNA/2'-O-methyl sequences corresponding to all possible combinations of such residues in a kissing aptamer loop complementary to the 6-nt loop of the TAR element of HIV-1. Three combinations of LNA/2'-O-methyl nucleoside analogues where one or two LNA units are located on the 3' side of the aptamer loop display an affinity for TAR below 1nM, i.e. one order of magnitude higher than the parent RNA aptamer. One of these combinations inhibits the TAR-dependent luciferase expression in a cell assay. PMID- 17276431 TI - Administration of exogenous ghrelin in obese patients with polycystic ovary syndrome: effects on plasma levels of growth hormone, glucose, and insulin. AB - OBJECTIVE: To assess the effects of the administration of exogenous ghrelin, a peptide with potent GH-releasing activity and glucose-enhancing and insulin lowering properties, in obese patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective, controlled study. SETTING: Academic research environment. PATIENT(S): Twenty obese women with PCOS, and 15 obese controls. INTERVENTION(S): Oral glucose tolerance test (OGTT) and ghrelin test (1 microg/kg i.v. bolus). MAIN OUTCOME MEASURE(S): Basal hormonal assays, including ghrelin, were performed. Glucose, insulin, and C-peptide were assessed in a fasting condition and during the OGTT. Growth hormone, insulin, and glucose were measured basally and every 15 minutes for 90 minutes after the injection of ghrelin. RESULT(S): Both groups showed an insulin response to the glucose load above the normal range. Significantly lower levels of ghrelin were detected in patients with PCOS compared to controls (108.96 +/- 27.65 Fmol/mL versus 162.47 +/- 42.23 Fmol/mL). Administration of ghrelin markedly enhanced GH levels in both groups (1,888.59 +/ 1,209.53 ng/mL and 1,639.95 +/- 631.79 ng/mL per 90 minutes as GH area under the curve, respectively), with a peak occurring 30 minutes after injection. Ghrelin also induced a trend toward an increase in plasma glucose levels, and a significant decrease in insulin concentrations in both groups. CONCLUSION(S): The injection of ghrelin seems to override the GH secretion defect in obese women with PCOS, and to induce glucoinsulinemic changes in both controls and obese patients with PCOS. PMID- 17276432 TI - Current alcohol use, hormone levels, and hot flashes in midlife women. AB - Current alcohol use is associated with a lower risk of hot flashes through a mechanism that does not include changes in sex steroid hormone levels. PMID- 17276433 TI - Initial experience with a donor egg bank. AB - OBJECTIVE: To report on the establishment of a commercial donor egg bank (CryoEggs International, LP) and to present our initial experience from the first four patients to receive eggs. DESIGN: Case report. SETTING: Private fertility clinic. PATIENT(S): The four recipient women were aged 43, 43, 40, and 33 years. All had cycle day FSH levels greater than 25 mIU/mL. All were given the option of fresh donor egg IVF but opted to use frozen donor oocytes. INTERVENTION(S): Purchased and quarantined frozen donor eggs were thawed and inseminated using intracytoplasmic sperm injection (ICSI). Subsequent embryos were transferred on day 3. MAIN OUTCOME MEASURE(S): Clinical pregnancy as defined by presence of cardiac activity. RESULT(S): There was a thawed egg survival rate of 76%, a fertilization rate of 74%, a pregnancy rate (PR) of 50%, with an average of 2.75 embryos per transfer and an implantation rate of 27%. CONCLUSION(S): Although very preliminary, these results indicate that more widespread use of frozen donor eggs obtained from a commercial egg bank may be feasible in the future, changing the landscape of donor egg IVF. PMID- 17276434 TI - Struma ovarii coincident with Hashimoto's thyroiditis: an unusual cause of hyperthyroidism. AB - OBJECTIVE: To report the identification of struma ovarii in a patient with a history of struma ovarii and new hyperthyroidism. DESIGN: Case report. SETTING: Academic research hospital. PATIENT(S): A woman with hyperthyroidism who has struma ovarii coincident with Hashimoto's thyroiditis. INTERVENTION(S): Laparoscopic salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Measurement of thyroid hormone parameters before and after surgery. RESULT(S): After removal of the second struma ovarii, hyperthyroidism resolved. CONCLUSION(S): In a patient with two different causes of abnormal thyroid function, it is important to seek an encompassing clinical scenario. PMID- 17276435 TI - Uterine leiomyomas express a molecular pattern that lowers retinoic acid exposure. AB - OBJECTIVE: To analyze expression of the retinoic acid signaling pathway genes that are involved in retinol metabolism, transport, transcriptional activation, and transcriptional products in spontaneous human leiomyomas. DESIGN: Laboratory study of human leiomyoma and patient-matched myometrial tissue. PATIENT(S): Eight women undergoing hysterectomy for symptomatic leiomyomas. INTERVENTION(S): Confirmation of an altered retinoic acid pathway analyzed by microarray, real time reverse transcription-polymerase chain reaction, Western blot, immunohistochemistry, and high-performance liquid chromatography (HPLC). MAIN OUTCOME MEASURE(S): Gene and protein expression. RESULT(S): Regardless of patient demographics and leiomyoma location and size, we found decreased expression of the major genes involved in retinoic acid pathway including alcohol dehydrogenase 1 (-3.97- +/- 0.03-fold), aldehyde dehydrogenase-1 (-3.1- +/- 0.07-fold), cellular retinol binding protein-1 (-2.62- +/- 0.04-fold), and cellular retinoic acid binding protein-1 (-2.42- +/- 0.20-fold). Cytochrome P450 (CYP 26A1), which is responsible for retinoic acid metabolism, was highly up-regulated in leiomyomas (+5.4- +/- 0.53-fold). Nuclear receptors demonstrated a complex pattern of under-expression (RARalpha, RARbeta, RXRalpha, RXRgamma) and over expression (RARgamma, RXRbeta) at both the mRNA and protein level. Differences in protein amounts were confirmed by Western blot. Finally, a reduced amount of cellular ATRA and 9-cis retinoic acid was confirmed by HPLC in leiomyomas compared with myometrial tissues. CONCLUSION(S): Molecular alterations in the retinoic acid pathway of leiomyomata result in a decrease in retinoic acid exposure. PMID- 17276436 TI - Assisted reproductive technology in the United States: 2001 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology registry. AB - OBJECTIVE: To summarize the procedures and outcomes of assisted reproductive technologies (ART) that were initiated in the United States in 2001. DESIGN: Data were collected electronically using the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System software and submitted to the American Society for Reproductive Medicine/SART Registry. PARTICIPANT(S): Three hundred eighty-five clinics submitted data on procedures performed in 2001. Data were collated after November 2002 [corrected] so that the outcomes of all pregnancies would be known. MAIN OUTCOME MEASURE(S): Incidence of clinical pregnancy, ectopic pregnancy, abortion, stillbirth, and delivery. RESULT(S): Programs reported initiating 108,130 cycles of ART treatment. Of these, 79,042 cycles involved IVF (with and without micromanipulation), with a delivery rate per retrieval of 31.6%; 340 were cycles of gamete intrafallopian transfer, with a delivery rate per retrieval of 21.9%; 661 were cycles of zygote intrafallopian transfer, with a delivery rate per retrieval of 31.0%. The following additional ART procedures were also initiated: 8,147 fresh donor oocyte cycles, with a delivery rate per transfer of 47.3%; 14,509 frozen ET procedures, with a delivery rate per transfer of 23.5%; 3,187 frozen ETs employing donated oocytes or embryos, with a delivery rate per transfer of 27.4%; and 1,366 cycles using a host uterus, with a delivery rate per transfer of 38.7%. In addition, 112 cycles were reported as combinations of more than one treatment type, 8 cycles as research, and 85 as embryo banking. As a result of all procedures, 29,585 deliveries were reported, resulting in 41,168 neonates. CONCLUSION(S): In 2001, there were more programs reporting ART treatment and a significant increase in reported cycles compared with 2000. PMID- 17276437 TI - Assessment of gonadotropin therapy in male hypogonadotropic hypogonadism. AB - The objective of this study was to determine the efficacy of gonadotropin therapy in men with hypogonadotropic hypogonadism. Gonadotropin therapy is a safe and effective therapy for hypogonadotropic hypogonadism. PMID- 17276438 TI - Carotid intima-media thickness is inversely associated with olive oil consumption. AB - BACKGROUND: Intima-media thickness (IMT) is a valid marker for generalized vascular disease whose main risk factors are associated with food habits and lifestyle. A Mediterranean food pattern may have a protective effect on cardiovascular mortality. OBJECTIVE: To assess the relationship between carotid IMT and olive oil consumption. METHODS: One hundred and ninety nine patients were randomly extracted from 1055 asymptomatic high cardiovascular risk participants at the AP-UNAV recruitment center of the PREDIMED (PREvencion con DIeta MEDiterranea) project. Demographic and clinical variables were collected, and a validated semiquantitative food frequency questionnaire (137 items) was administered at the inclusion interview. A B-mode ultrasound imaging technique was used to measure the mean common carotid IMT. RESULTS: The mean age was 67.3 years and 53.3% were women. Energy-adjusted olive oil consumption quintiles were assessed as the main exposure after adjusting for potential dietary and non dietary confounders. Using continuous carotid IMT as the outcome in an ANCOVA analysis, the adjusted IMT means throughout quintiles showed an inverse association with a plateau after the second quintile, with statistical differences when the adjusted IMT mean of the merged four upper quintiles were compared with the lowest quintile (p<0.05). The averaged (both sides) mean IMT of the common carotid was dichotomised and values above the median (0.804 mm) were used to identify carotid atherosclerotic damage. We also found an inverse association of olive oil consumption with high IMT, throughout the second to the fifth quintile as compared with the lowest quintile. The adjusted OR was of 0.08 (95% confidence interval, CI, of 0.02-0.37; p=0.001) after merging the four upper quintiles. CONCLUSION: The inverse association between the olive oil consumption and the carotid IMT could suggest a protective role of olive oil against the development of carotid atherosclerosis in persons at high cardiovascular risk. PMID- 17276439 TI - A digital database of wrist bone anatomy and carpal kinematics. AB - The skeletal wrist consists of eight small, intricately shaped carpal bones. The motion of these bones is complex, occurs in three dimensions, and remains incompletely defined. Our previous efforts have been focused on determining the in vivo three-dimensional (3-D) kinematics of the normal and abnormal carpus. In so doing we have developed an extensive database of carpal bone anatomy and kinematics from a large number of healthy subjects. The purpose of this paper is to describe that database and to make it available to other researchers. CT volume images of both wrists from 30 healthy volunteers (15 males and 15 females) were acquired in multiple wrist positions throughout the normal range of wrist motion. The outer cortical surfaces of the carpal bones, radius and ulna, and proximal metacarpals were segmented and the 3-D motion of each bone was calculated for each wrist position. The database was constructed to include high resolution surface models, measures of bone volume and shape, and the 3-D kinematics of each segmented bone. The database does not include soft tissues of the wrist. While there are numerous digital anatomical databases, this one is unique in that it includes a large number of subjects and it contains in vivo kinematic data as well as the bony anatomy. PMID- 17276440 TI - A new general approach to purify proteins from complex mixtures. AB - The selection of chromatography media and their sequential use represent a major difficulty to isolate a single protein from very crude protein extracts. The process described here consists of two main steps: (i) a rational selection of few media from a relatively large collection and (ii) the definition of the sequence of columns to get the best purity of the target protein. From the first step, one sorbent is selected for its properties to capture the protein to purify, regardless whether other protein impurities are also co-adsorbed; then 5 7 other complementary sorbents are identified to remove impurities but without interacting with the target protein under the same buffering conditions. The second step consists in superimposing sorbents under a cascade manner with the sorbent in charge to capture the target protein located in the last position. Non adsorbed proteins are eliminated in the flowthrough; other impurities are progressively removed by the sorbent sequence and the target protein is finally desorbed and isolated from the last sorbent using an optimized gradient. All operations are performed with a single adsorption buffer for all columns and all monitoring performed by means of mass spectrometry associated with ProteinChip arrays and polyacrylamide gel electrophoresis. Examples of protein isolation/identification from human serum are described namely thyroxin-binding proteins and transferrin. The first is isolated thanks to a series of dye chromatography media, the second (transferrin) using current chromatographic media. In both cases the target proteins were purified at a level estimated of about 95% and 85%, respectively. Isolated proteins were pure enough for the purpose of formal identification by either peptide fingerprinting or sequencing. PMID- 17276441 TI - Trends in sample preparation for classical and second generation proteomics. AB - Sample preparation is a fundamental step in the proteomics workflow. However, it is not easy to find compiled information updating this subject. In this paper, the strategies and protocols for protein extraction and identification, following either classical or second generation proteomics methodologies, are reviewed. Procedures for: tissue disruption, cell lysis, sample pre-fractionation, protein separation by 2-DE, protein digestion, mass spectrometry analysis, multidimensional peptide separations and quantification of protein expression level are described. PMID- 17276442 TI - Reversed-phase liquid chromatography column testing and classification: physicochemical interpretation based on a wide set of stationary phases. AB - The high number of stationary phases commercially available for liquid chromatography makes the choice of the analyst a real headache. In order to provide a tool to carry out this choice on objective basis, the present work proposes interpretations of the column classifications obtained, thanks to a previously described testing procedure. The meaning of principal components was attributed to crossing over information carried by loading plots and groups revealed by hierarchical cluster analysis (HCA) on the corresponding score plots. At high solvent ratio, the retention seemed to be governed by enthalpy, whereas at low solvent ratio, entropic phenomena were predominating. Finally, the behavior of known families of RPLC columns was studied giving rise either to homogeneous groups like polar embedded grafts columns or to scattered families like Aqua type columns. PMID- 17276444 TI - An HII liquid crystal-based delivery system for cyclosporin A: physical characterization. AB - In the present study we demonstrate that large quantities of cyclosporin A and three dermal penetration enhancers (phosphatidylcholine, ethanol, or Labrasol) can be solubilized into reverse hexagonal (HII) liquid crystalline structures composed of monoolein, tricaprylin, and water. The microstructural characteristics of these complex multi-component systems were elucidated by rheological, SAXS, and DSC measurements. Addition of up to 20 wt% phosphatidylcholine improved significantly the elastic properties of the systems (lower values of tandelta) and increased the thermal stability of the mesophases enabling us to solubilize up to 6 wt% cyclosporin A and two other enhancers (Labrasol and ethanol) to obtain stable mesophases at physiological temperature. Rheological measurements revealed that solubilization of cyclosporin A alone has a destabilizing effect on the reverse hexagonal phases: it caused a deterioration in the elastic properties of the systems, leading to more liquid-like behavior and resulting in very short relaxation times (0.04-0.1 s). Labrasol, solubilized at high concentrations (up to 12 wt%) into the liquid crystals, also demonstrated a destabilizing effect on the HII structure: the decreasing elasticity of the system was attributed to Labrasol's presumed locus at the interface and its ability to bind water, as shown by DSC measurements. Ethanol had a destabilizing effect similar to that of Labrasol, yet the effect appeared to be more pronounced, probably due to its higher water-binding capability. PMID- 17276443 TI - Real dispersion of isolated fumed silica nanoparticles in highly filled PMMA prepared by high energy ball milling. AB - Fumed silica nanoparticles with 14 nm of diameter were blended with poly(methylmethacrylate), PMMA, by means of a high energy ball milling process. AFM analysis revealed how this process of blending allows obtaining a very homogeneous dispersion of the nanoparticles within the PMMA. Furthermore, it was observed that the properties of the composite are highly dependent on the active milling time: (i) SEM inspection showed that the particle size of the silica-PMMA nanocomposite decreases and (ii) DSC analysis demonstrated that the Tg also decreases due to a reduction in the molecular weight of the PMMA caused by chain scission during the high energy blending process. Two Tg's were obtained in the case of the nanocomposite when milling times were higher than 6 h, one of them being even higher than that of the PMMA without being subjected to the HEBM process. This result was assigned to surface-induced molecular weight segregation near the nanoparticles surface. It has been demonstrated the possibility of preparing transparent nanocomposites with excellent moldability. PMID- 17276445 TI - A general contact mechanical formulation of multilayered structures and its application to deconvolute thickness/mechanical properties of glue used in surface force apparatus. AB - Currently data obtained from surface force apparatus experiments are convoluted with the mechanical response of glue of unknown thickness, used to bond mica sheets to the substrates. This paper describes a formulation to precisely deconvolute out the forces between the mica sheets by determining the thickness of glue, knowing the mechanical properties of the glue. The formulation consists of a general solution based on the noniterative Hankel transform of the Laplace equation. The generality is achieved by treating all the layers except the one in contact as an effective lumped system consisting of a set of springs in series, where each spring represents a layer. The solution is validated by nanoindentation of trilayer systems consisting of layers with widely diverse mechanical properties, some differing from each other by three orders of magnitude. SFA experiments are done with carefully metered slabs of glue. The proposed method is validated by comparing the actual glue thicknesses with those determined using the present analysis. PMID- 17276446 TI - Electrophysiologic characteristics and outcome of segmental ostial superior vena cava isolation in patients with paroxysmal atrial fibrillation initiated by superior vena cava ectopy: comparison with pulmonary vein isolation. AB - BACKGROUND: This study investigated the electrophysiologic characteristics and outcome of superior vena cava (SVC) segmental ostial isolation (SOI) in patients with SVC-initiated paroxysmal atrial fibrillation (PAF). METHODS: Ninety-five patients with PAF underwent pulmonary vein (PV) SOI using a basket catheter whether the PAF originating from PVs was observed or not. Fifteen of those patients also underwent SVC SOI in the same manner due to evidence of SVC origin PAF. RESULTS: The SVC musculature networks and electrical connections with the atrium (multiple separate electrical connections in 10, multiple separate musculature networks with separate electrical connections in 1, and a continuous broad electrical connection in 4 SVCs) were similar to those of the PV musculature. However, the occurrence of an electrical connection recovery after SOI in patients with recurrent atrial fibrillation was lower for SVCs (25%) than PVs (58%). CONCLUSIONS: Superior vena cava SOI appears to have a lower recurrent conduction rate than PV SOI. PMID- 17276447 TI - Superiority of the limb leads over the precordial leads on the 12-lead ECG in monitoring fluctuating fluid overload in a patient with congestive heart failure. AB - A 78-year old woman with congestive heart failure had fluctuating peripheral edema and weights while hospitalized and was subsequently followed in the cardiac clinic. Sums of the amplitudes of the QRS complexes for the leads I + II (SigmaQRS(I + II)), the 6 limb leads (SigmaQRS(6L)), the 6 precordial leads (SigmaQRS(V1-V6)), and all 12 leads (SigmaQRS(12L)) were calculated. Analysis showed that SigmaQRS(I + II) and SigmaQRS(6L) correlated very well with corresponding weights (r = 0.78, P .01 and r = 0.75, P = .02, respectively), whereas SigmaQRS(V1-V6) and SigmaQRS(12L) did not (r = 0.20, P = .60 and r = 0.47, P = .20, respectively). The reason for the poor correlation of the latter two was the erratic values of SigmaQRS(V1-V6) in serial electrocardiogram recordings. SigmaQRS(I + II) and SigmaQRS(6L) are useful for serially following patients with congestive heart failure and peripheral edema. PMID- 17276448 TI - An electrocardiogram marker to detect paroxysmal atrial fibrillation. AB - An electrocardiogram marker to detect patients who have paroxysmal atrial fibrillation (PAF) is reported. The data set of ECG records made available by PhysioNet for Cardiology Challenge 2001 was used. The method uses a filtered time series with a frequency range between 3 and 9 Hz obtained from the electrocardiogram record. Typically, frequencies observed when a patient is in atrial fibrillation and atrial flutter is within this frequency range. Filtering was done using wavelets. Thereafter, the temporal properties of this filtered time series are studied. The temporal properties studied are the standard deviation, standard deviation of successive differences, and the length of the ellipse in the Poincare plot. The results indicate that these temporal properties of patients with PAF are depressed compared to the healthy group. A marker based on these temporal properties shows promise in detecting PAF when patients are in normal sinus rhythm. Results also show that the values for these temporal properties for a patient with PAF show little variation with time, and its measure is not dependent on the time of occurrence of a PAF episode. PMID- 17276450 TI - Comparison of the Selvester QRS scoring system applied on standard versus high resolution electrocardiographic recordings. AB - A comparison was performed between the points measured using the Selvester QRS scoring system in 60 electrocardiograms (ECGs) displayed in both a standard format as well as a 4-fold magnified (quad-plot) format. Fifty criteria (a maximum possibility of 31 points) were evaluated in each ECG. The data indicate that in 50% of the ECGs, an identical number of points were measured. However, there was a single point difference in 31%, 2 points in 15%, and more than 2 points in 4%. The differences were primarily because of points scored on the quad plot but not on the standard ECG. Thus, a systematic underestimation of infarct size may occur when the Selvester QRS score is measured manually from a standard ECG. PMID- 17276449 TI - Dropped beat: Sir William Osler's tenuous embracement of the electrocardiogram. PMID- 17276451 TI - Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. AB - BACKGROUND: Reference ranges for electrocardiogram (ECG) intervals, heart rate, and QRS axis in general use by medical personnel and ECG readers are unrepresentative of true age- and sex-related values in large populations and are not based on modern electrocardiographic and ECG reading technology. METHODS AND RESULTS: The results of ECG interpretation by cardiologists using digital technology for viewing and interpreting ECGs were compiled from single, baseline ECGs of 79,743 individuals included in pharmaceutical company-sponsored clinical trials. Women comprised 48% of the total population. Ages ranged from 3 months to 99 years, and the bulk of the population (56%) was aged 40 to 70 years. Striking differences in numerical ECG values based on age and sex were observed. A subgroup of 46,129 individuals with a very low probability of cardiovascular disease was identified. The following were the reference ranges for this subgroup, determined using the 2nd and 98th percentiles: heart rate, 48 to 98 beats/min; PR interval, 113 to 212 milliseconds; QRS interval, 69 to 109 milliseconds; frontal plane QRS axis, -40 degrees to 91 degrees ; QT interval, 325 to 452 milliseconds; QTc-Bazett, 361 to 457 milliseconds; and QTc-Fridericia, 359 to 445 milliseconds. There were marked age- and sex-related variations in the reference ranges of this subgroup, and they differ substantially from previously reported norms. Small differences were observed in ECG values obtained using our digital methods as compared with readings done using paper tracings and values computed by 2 commercial computer algorithms. CONCLUSIONS: We observed large differences in electrocardiographic heart rate, interval, and axis reference ranges in this study compared with those reported previously and with reference ranges in general use. We also observed a large influence of age and sex upon normal values. Very large cohorts are required to fully assess age- and sex related variation of reference ranges. Electrocardiographic reference ranges should be modernized. PMID- 17276452 TI - Ljuba Bacharova: interview with Professor Leonid Ivanovich Titomir, DSc. PMID- 17276453 TI - Accessory-pathway block on alternate beats in the Wolff-Parkinson-White syndrome: supernormal conduction as the mechanism. AB - The Holter monitor electrocardiograms were taken from 2 patients with intermittent Wolff-Parkinson-White syndrome. In these patients, when the heart rate was increased, accessory-pathway block on alternate beats was found and was maintained for a considerably long period. In one patient, when accessory-pathway block on alternate beats was found, a ventricular extrasystole occurred. After the long compensatory pause after that extrasystole, a sinus impulse was blocked in the accessory pathway, showing that the effective refractory period of the accessory pathway is markedly long. These findings strongly suggest that alternate sinus impulses fell in the supernormal period of the accessory pathway. An attempt was made to explain the mechanism of accessory-pathway block on alternate beats by using the concept of supernormal conduction in the accessory pathway, in the same way as in bundle-branch block on alternate beats. PMID- 17276454 TI - Use of bifunctional hybrid beta-lactamases for epitope mapping and immunoassay development. AB - Mapping of epitopes is a crucial step for the study of immune pathways, the engineering of vaccines and the development of immunoassays. In this work, the Bacillus licheniformis beta-lactamase BlaP has been engineered to display heterologous polypeptides in a permissive and solvent-exposed loop. When combined with phage display, this modified enzyme can be used for epitope mapping by cloning random gene fragments. The procedure presented in this paper allows the selection of large infectious phage libraries with high diversity and efficient beta-lactamase activities. A useful aspect of the proposed technique results from the possibility of using the beta-lactamase activity carried by phages to evaluate the proportion of immobilised phages during the successive enrichment steps of the library or competition experiments with the selected phages. Another advantage of the technique derives from the fact that the epitope is selected as a bifunctional hybrid protein, which can be overproduced and purified. The resulting recombinant protein associates an epitope with a specific and efficient enzymatic activity. This constitutes an original tool for immunoassay development. A virus influenza hemagglutinin (HA1)-gene fragment library has been generated with this system and used to identify a linear epitope. PMID- 17276455 TI - Seminal proteins but not sperm induce morphological changes in the Drosophila melanogaster female reproductive tract during sperm storage. AB - In most insects, sperm transferred by the male to the female during mating are stored within the female reproductive tract for subsequent use in fertilization. In Drosophila melanogaster, male accessory gland proteins (Acps) within the seminal fluid are required for efficient accumulation of sperm in the female's sperm storage organs. To determine the events within the female reproductive tract that occur during sperm storage, and the role that Acps and sperm play in these events, we identified morphological changes that take place during sperm storage in females mated to wild-type, Acp-deficient or sperm-deficient males. A reproducible set of morphological changes occurs in a wild-type mating. These were categorized into 10 stereotypic stages. Sperm are not needed for progression through these stages in females, but receipt of Acps is essential for progression beyond the first few stages of morphological change. Furthermore, females that received small quantities of Acps reached slightly later stages than females that received no Acps. Our results suggest that timely morphological changes in the female reproductive tract, possibly muscular in nature, may be needed for successful sperm storage, and that Acps from the male are needed in order for these changes to occur. PMID- 17276456 TI - Role of an alternatively spliced form of alphaII-spectrin in localization of connexin 43 in cardiomyocytes and regulation by stress-activated protein kinase. AB - Decreases in the expression of connexin 43 and the integrity of gap junctions in cardiac muscle, induced by the constitutive activation of the c-Jun N-terminal kinase (JNK) signaling pathway, have been linked to conduction defects and sudden cardiac failure in mice [Petrich BG, Gong X , Lerner DL , Wang X , Brown JH , Saffitz JE , Wang Y. c-Jun N-terminal kinase activation mediates downregulation of connexin 43 in cardiomyocytes. Circ Res. 91 (2002) 640-647; B.G. Petrich, B.C. Eloff, D.L. Lerner, A. Kovacs, J.E. Saffitz, D.S. Rosenbaum, Y. Wang, Targeted activation of c-Jun N-terminal kinase in vivo induces restrictive cardiomyopathy and conduction defects. J. Biol. Chem. 2004;279: 15330-15338]. We examined the membrane cytoskeletal protein, alphaII-spectrin, which associates with connexin 43, to learn if changes in its association with connexin 43 are linked to the instability of gap junctions. Several forms of alphaII-spectrin are expressed in the heart, including one, termed alphaII-SH3i, which contains a 20-amino-acid sequence next to the SH3 domain of repeat 10. In adult mouse heart, antibodies to all forms of alphaII-spectrin labeled the sarcolemma, transverse ("t-") tubules and intercalated disks of cardiomyocytes. In contrast, antibodies specific for alphaII-SH3i labeled only gap junctions and transverse tubules. In transgenic hearts, in which the JNK pathway was constitutively activated, alphaII-SH3i was lost specifically from gap junctions but not from t-tubules while other isoforms of alphaII-spectrin were retained at intercalated disks. Immunoprecipitations confirmed the decreased association of alphaII-SH3i with connexin 43 in transgenic hearts compared to controls. Furthermore, activation of JNK in neonatal myocytes blocked the formation of gap junctions by exogenously expressed Cx43-GFP fusion protein. Similarly, overexpression of the SH3i fragment in the context of repeats 9-11 of alphaII-spectrin specifically caused the accumulation of Cx43-GFP in the perinuclear region and inhibited its accumulation at gap junctions. These results support a critical role for the alphaII-SH3i isoform of spectrin in intracellular targeting of Cx43 to gap junctions and implicates alphaII-SH3i as a potential target for stress signaling pathways that modulate intercellular communication. PMID- 17276457 TI - A divalent metal-mediated switch controlling protein-induced DNA bending. AB - Architectural proteins that reconfigure the paths of DNA segments are required for the establishment of functional interfaces in many genomic transactions. A single-chain derivative of the DNA architectural protein integration host factor was found to adopt two stable conformational states in complex with a specific DNA target. In the so-called open state, the degree of protein-induced DNA bending is reduced significantly compared with the closed state. The conformational switch between these states is controlled by divalent metal binding in two electronegative zones arising from the lysine-to-glutamate substitution in the protein body proximal to the phosphate backbone of one DNA arm. We show that this switch can be employed to control the efficiency of site specific recombination catalyzed by lambda integrase. Introduction of acidic residues at the protein-DNA interface holds potential for the design of metal mediated switches for the investigation of functional relationships. PMID- 17276458 TI - The Grb2/PLD2 interaction is essential for lipase activity, intracellular localization and signaling in response to EGF. AB - The adaptor protein Grb2 associates with phospholipase D2 (PLD2), but it is not known if this interaction is necessary for the functionality of the lipase in vivo. We demonstrate that stable short hairpin RNA (shRNA)-based silencing of Grb2, a critical signal transducer of the epidermal growth factor receptor (EGFR) and linker to the Ras/Erk pathway, resulted in the reduction of PLD2 activity in COS7 cells. Transfection of a Grb2 construct refractory to shGrb2 silencing (XGrb2(SiL)) into the Grb2-knockdown cells (COS7(shGrb2)), resulted in the nearly full rescue of PLD2 activity. However, Grb2-R86K, an SH2-deficient mutant of Grb2 that is incapable of binding to PLD2, failed to induce an enhancement of the impaired PLD2 activity in COS7(shGrb2) cells. Grb2 and PLD2 are directly associated and Grb2 is brought down with anti-myc antibodies irrespective of the presence or absence of EGFR activation. Immunofluorescence microscopy showed that co-transfected PLD2 and Grb2 re-localize to Golgi-like structures after EGF stimulation. Since this was not observed in cotransfection experiments with Grb2 and PLD2-Y169/179F, a lipase mutant that does not bind to Grb2, we inferred that Grb2 serves to hijack PLD2 to the perinuclear Golgi region through its SH2 domain. Supporting this is the finding that the primary cell line HUVEC expresses PLD2 diffusely in the cytoplasm and in the perinuclear Golgi region, where PLD2 and Grb2 colocalize. Such colocalization in primary cells increased after stimulation with EGF. These results demonstrate for the first time that the presence of Grb2 and its interaction with localized intracellular structures is essential for PLD2 activity and signaling in vivo. PMID- 17276459 TI - Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. AB - Using a combined master equation and kinetic cluster approach, we investigate RNA pseudoknot folding and unfolding kinetics. The energetic parameters are computed from a recently developed Vfold model for RNA secondary structure and pseudoknot folding thermodynamics. The folding kinetics theory is based on the complete conformational ensemble, including all the native-like and non-native states. The predicted folding and unfolding pathways, activation barriers, Arrhenius plots, and rate-limiting steps lead to several findings. First, for the PK5 pseudoknot, a misfolded 5' hairpin emerges as a stable kinetic trap in the folding process, and the detrapping from this misfolded state is the rate-limiting step for the overall folding process. The calculated rate constant and activation barrier agree well with the experimental data. Second, as an application of the model, we investigate the kinetic folding pathways for human telomerase RNA (hTR) pseudoknot. The predicted folding and unfolding pathways not only support the proposed role of conformational switch between hairpin and pseudoknot in hTR activity, but also reveal molecular mechanism for the conformational switch. Furthermore, for an experimentally studied hTR mutation, whose hairpin intermediate is destabilized, the model predicts a long-lived transient hairpin structure, and the switch between the transient hairpin intermediate and the native pseudoknot may be responsible for the observed hTR activity. Such finding would help resolve the apparent contradiction between the observed hTR activity and the absence of a stable hairpin. PMID- 17276461 TI - Lobe IB of the ATPase domain of Kar2p/BiP interacts with Ire1p to negatively regulate the unfolded protein response in Saccharomyces cerevisiae. AB - The endoplasmic reticulum HSP70 chaperone BiP/Kar2p is both the sensor for the unfolded protein response (UPR) in the yeast Saccharomyces cerevisiae and a target of transcriptional up-regulation by this signaling pathway. In this study, the molecular form of Kar2p that interacts with the Ire1p transmembrane receptor kinase to inhibit UPR signaling was shown to be the substrate-free, ATP-bound conformation. Oligosaccharide shielding experiments localized the binding site for Ire1p to the top of the back face of lobe IB of the Kar2p ATPase domain. The interaction between Kar2p and Ire1p is abolished by substitution of glutamic acid for glutamine 88, a residue on the surface of lobe IB that is likely to be shielded by ectopic oligosaccharide side-chains that also prevented the interaction between the two proteins. Glutamine 88 is conserved significantly throughout the HSP70 chaperone family and others have shown that the NMR resonances of the corresponding glutamine residue in Thermus thermophilus DnaK display chemical shift perturbations between the ATP-bound and ADP-bound states and in the presence of a substrate peptide. We conclude that glutamine 88 is part of or close to the Ire1p-binding site displayed on the ATP-bound conformation of Kar2p. Binding of an unfolded polypeptide to the substrate-binding domain of Kar2p could alter the positioning of glutamine 88 and other residues on lobe IB involved in binding Ire1p, releasing Ire1p for activation of UPR signaling. PMID- 17276460 TI - Elucidation of the active conformation of the APS-kinase domain of human PAPS synthetase 1. AB - Bifunctional human PAPS synthetase (PAPSS) catalyzes, in a two-step process, the formation of the activated sulfate carrier 3'-phosphoadenosine 5'-phosphosulfate (PAPS). The first reaction involves the formation of the 5'-adenosine phosphosulfate (APS) intermediate from ATP and inorganic sulfate. APS is then further phosphorylated on its 3'-hydroxyl group by an additional ATP molecule to generate PAPS. The former reaction is catalyzed by the ATP-sulfurylase domain and the latter by the APS-kinase domain. Here, we report the structure of the APS kinase domain of PAPSS isoform 1 (PAPSS1) representing the Michaelis complex with the products ADP-Mg and PAPS. This structure provides a rare glimpse of the active conformation of an enzyme catalyzing phosphoryl transfer without resorting to substrate analogs, inactivating mutations, or catalytically non-competent conditions. Our structure shows the interactions involved in the binding of the magnesium ion and PAPS, thereby revealing residues critical for catalysis. The essential magnesium ion is observed bridging the phosphate groups of the products. This function of the metal ion is made possible by the DGDN-loop changing its conformation from that previously reported, and identifies these loop residues unambiguously as a Walker B motif. Furthermore, the second aspartate residue of this motif is the likely candidate for initiating nucleophilic attack on the ATP gamma-phosphate group by abstracting the proton from the 3'-hydroxyl group of the substrate APS. We report the structure of the APS-kinase domain of human PAPSS1 in complex with two APS molecules, demonstrating the ability of the ATP/ADP-binding site to bind APS. Both structures reveal extended N termini that approach the active site of the neighboring monomer. Together, these results significantly increase our understandings of how catalysis is achieved by APS-kinase. PMID- 17276462 TI - An index to measure the effects of temperature change on trophic interactions. AB - Experimental studies document the fact that environmental temperature changes can affect the timing of interactions in many consumer-resource systems through altered, or shifted, phenologies of the species involved. We develop a simple mathematical model that shows one method to measure, quantitatively, the magnitude of the shift. Under different temperature regimes we compute the intersection of two regions in a joint phenology space: the region where temporal interactions can occur and the region where particular-sized predators consume particular-sized prey. The area of the intersection provides a numerical value for measuring the effective interaction. A comparison of the areas for different temperature histories defines an index, or yardstick, for quantitatively assessing the effects of temperature variations on phenological shifts. PMID- 17276463 TI - Role of non-neuronal cholinergic system in breast cancer progression. AB - We have previously reported the expression of functional muscarinic acetylcholine receptors (mAChR) in two different murine mammary adenocarcinoma cell lines LM2 and LM3. Activation of mAChR with carbachol (CARB) increased proliferation in both tumor cell lines in a concentration-dependent manner. In LM3 cells CARB promoted proliferation via M(3) receptor activation by inositol 1,4,5 triphosphate and nitric oxide (NO) production. CARB-induced LM2 cells proliferation needed both M(2) and M(1) receptor activation increasing prostaglandin E(2) liberation and arginase catabolism respectively. Our present results indicate that CARB stimulates LM2 and LM3-induced angiogenesis and tumor growth. This activation follows different patterns. In LM2 tumor, M(1) and M(2) receptors activation stimulates neovascularization by arginase II and cyclooxygenase-2 (COX-2)-derived products while M(1) and M(3) receptors mediate CARB-induced tumor growth by the same effector enzymes. In LM3 tumor, we observe that M(1) and M(2) receptors are involved in agonist-stimulated angiogenesis by COX and NOS1-derived products while tumor growth is stimulated by M(3) and M(2) receptors activation and COX-2-derived prostanoids. Taken together these data present, at least in part, a picture of the regulation that different mAChR subtypes activation exerts on angiogenesis and growth of two different murine mammary adenocarcinomas. PMID- 17276464 TI - In vivo release of non-neuronal acetylcholine from human skin by dermal microdialysis: effects of sunlight, UV-A and tactile stimulus. AB - Non-neuronal acetylcholine (ACh) is expressed in epithelial, endothelial and immune cells. For example, the in vivo release of ACh from the human skin pretreated with botulinum toxin has recently been demonstrated. In the present experiments the effects of light (sunlight and solar radiation by a commercial UV A applier) and of a tactile stimulus on the release of non-neuronal ACh were investigated. Release of ACh from the proximal and distal shin, i.e. anterior tibial region, was measured by dermal microdialysis in 20 min samples over a time period of at least 140 min. Control experiments were performed in a dark room throughout. In some experiments volunteers were exposed to sunshine (80-140 min) or the shin region was illuminated (80-95 min) by a commercial UV-A lamp (400 W at a distance of 50 cm). In control experiments ACh release between 20 and 80 min (B1) amounted to 118+/-32 pmol (n=17) and gradually declined between 80 and 140 min (B2) to 112+/-34 pmol, resulting in a B2/B1 ratio of 0.95. When the skin was exposed to sunlight ACh release increased from 205+/-58 pmol (B1) to 349+/-122 pmol resulting in a B2/B1 ratio of 1.70. UV-A radiation, however, had no significant effect on the B2/B1 ratio. When very smooth tactile stimuli were applied by a cotton wool tip for 20 min to the skin close to the microdialysis membranes in a dark room, ACh release was increased from 9+/-2 pmol/20 min to 52+/-36 (n=7). In conclusion, the in vivo release of ACh from the human skin appears to be regulated by external stimuli like sunlight and tactile stimuli. PMID- 17276465 TI - Importance of dental records for victim identification following the Indian Ocean tsunami disaster in Thailand. AB - OBJECTIVES: To determine the usefulness of dental records for victim identification following the Indian Ocean tsunami disaster in Thailand, and to evaluate the dental identification system in Thailand, the homeland of a large number of the victims. STUDY DESIGN: A descriptive study conducted at the Thai Tsunami Repatriation Centre in Phangnga Province one year after the tsunami hit Thailand on the 26th December 2004. METHODS: The dental records of 3750 dead bodies and 3547 missing persons in the Thai Tsunami Victim Identification (TTVI) database, updated on 12th December 2005, were analysed. RESULTS: The identification rate of missing persons with dental records was significantly higher than that of those without (P<0.01). Most victims identified by dental records were returned home within the first four months after the disaster. Dental records were the primary identifier in 46.2% of those identified. However, among the Thai citizens reported missing, only 2.0% used dental identification, 18.1% had dental charts and 0.8% had dental X-rays. In addition, only 7.4% of Thai dental records could be used for dental identification and one-third of Thai victims remained the majority of those unidentified. CONCLUSIONS: Based on this study, the usefulness of dental records for victim identification in a disaster was confirmed. The dental identification system for nationals of Thailand could not work efficiently due to lack of dental records and insufficient recorded detail. PMID- 17276466 TI - Increases in asthma hospital admissions associated with the end of the summer vacation for school-age children with asthma in two cities from England and Scotland. AB - In school-age asthmatics, an increase in hospitalizations has been reported in early autumn. This increase in admissions is conjectured to be associated with the return back to school. In the UK schools in England complete their summer vacations 2 weeks later than in Scotland and so there should be a lag between the two countries in the increase in asthma episode. Daily hospital asthma admission data from Aberdeen (in Scotland) and Doncaster (in England) for the period July 23rd to October 8th for years 1999-2004 were included in the analysis. There are peaks in hospitalization after the return back to school for both Aberdeen and Doncaster with the peak for Doncaster appearing 2 weeks after Aberdeen. This study has demonstrated peaks in admissions in school-age children around the return back to school in two cities where different school return dates were reflected in a 2-week lag effect. These data therefore provide strong evidence that peaks in admissions are associated with the end of the summer holidays. PMID- 17276468 TI - [Useful imaging in maxillofacial surgery. Part II: practical applications]. AB - Various pathologic patterns are discussed with advice on appropriate radiographic imaging. The choice of the most suitable modality for each condition depends on the need to obtain the most accurate results. Panoramic radiography remains a basic and low cost method. Choice of CT or MR as the principal or only modality depends on anatomic patterns: CT being preferred for bone and cavities, MR for soft tissue and cavity content. Much progress has been made in MR machines and the variety of sequences enables high discrimination between normal and pathologic tissues. PMID- 17276469 TI - [Mandibular chloroma]. AB - CASE REPORT: A 23 year-old girl was admitted for a facial tumefaction, fixed to the mandible. The X-rays showed a fuzzy osteolytic lesion of the mandibular angle. The CT-scan confirmed the rupture of the cortical bone and the extension to the soft tissue. Biopsy provided the diagnosis of granulocytic monoblastic sarcoma (chloroma). Chemotherapy was efficient. DISCUSSION: Mandibular localizations of chloroma are rare. Granulocytic monoblastic sarcoma is a localized tumor made of extramedullar immature granulocytes, in general associated (or more rarely preceded by) with leukemia. Early diagnosis is important because high dose chemotherapy induction may completely cure leukemia. PMID- 17276470 TI - Estrogen receptor signaling pathways in human non-small cell lung cancer. AB - Lung cancer is the most common cause of cancer mortality in male and female patients in the US. The etiology of non-small cell lung cancer (NSCLC) is not fully defined, but new data suggest that estrogens and growth factors promote tumor progression. In this work, we confirm that estrogen receptors (ER), both ERalpha and ERbeta, occur in significant proportions of archival NSCLC specimens from the clinic, with receptor expression in tumor cell nuclei and in extranuclear sites. Further, ERalpha in tumor nuclei was present in activated forms as assessed by detection of ER phosphorylation at serines-118 and -167, residues commonly modulated by growth factor receptor as well as steroid signaling. In experiments using small interfering RNA (siRNA) constructs, we find that suppressing expression of either ERalpha or ERbeta elicits a significant reduction in NSCLC cell proliferation in vitro. Estrogen signaling in NSCLC cells may also include steroid receptor coactivators (SRC), as SRC-3 and MNAR/PELP1 are both expressed in several lung cell lines, and both EGF and estradiol elicit serine phosphorylation of SRC-3 in vitro. EGFR and ER also cooperate in promoting early activation of p42/p44 MAP kinase in NSCLC cells. To assess new strategies to block NSCLC growth, we used Faslodex alone and with erlotinib, an EGFR kinase inhibitor. The drug tandem elicited enhanced blockade of the growth of NSCLC xenografts in vivo, and antitumor activity exceeded that of either agent given alone. The potential for use of antiestrogens alone and with growth factor receptor antagonists is now being pursued further in clinical trials. PMID- 17276471 TI - Novel Hedgehog pathway targets against basal cell carcinoma. AB - The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence. PMID- 17276473 TI - St. John's wort and irinotecan-induced diarrhea. PMID- 17276472 TI - Thio-dimethylarsinate is a common metabolite in urine samples from arsenic exposed women in Bangladesh. AB - Over the last 6 years, much work on arsenic species in urine samples has been directed toward the determination of the reduced dimethylated arsenic species, DMA(III), because of its high toxicity and perceived key role in the metabolism of inorganic arsenic. Recent work, however, has suggested that DMA(III) may at times have been misidentified because its chromatographic properties can be similar to those of thio-dimethylarsinate (thio-DMA). We analyzed by HPLC-ICPMS (inductively coupled plasma mass spectrometry) urine samples from 75 arsenic exposed women from Bangladesh with total arsenic concentrations ranging from 8 to 1034 microg As/L and found that thio-DMA was present in 44% of the samples at concentrations ranging mostly from trace amounts to 24 microg As/L (one sample contained 123 microg As/L). Cytotoxicity testing with HepG2 cells derived from human hepatocarcinoma indicated that thio-DMA was about 10-fold more cytotoxic than dimethylarsinate (DMA). The widespread occurrence of thio-DMA in urine from these arsenic-exposed women suggests that this arsenical may also be present in other urine samples and has so far escaped detection. The work highlights the need for analytical methods providing specific determinations of arsenic compounds in future studies on arsenic metabolism and toxicology. PMID- 17276474 TI - Parametric harmonic-to-fundamental ratio contrast echocardiography: a novel approach to identification and accurate measurement of left ventricular area under variable levels of ultrasound signal attenuation. AB - OBJECTIVES: We introduced a harmonic-to-fundamental ratio (HFR) of the radiofrequency (RF) signals that reduces confounding effects of attenuation. We studied whether HFR analysis of RF signals received from contrast microbubbles allows accurate measurement of the left ventricular (LV) cavity area under varying levels of attenuation. BACKGROUND: Attenuation is a fundamental problem in ultrasound imaging and limits the use of clinical echocardiography. METHODS: RF data from short axis systolic and diastolic scans were obtained from 14 open chest dogs following left-atrial bolus of Optison. Attenuation was induced by interposed silicone pads calibrated to induce 7dB or 14dB reductions of the backscattered RF signal. RF images were reconstructed from the RF signals, HFR values calculated for each image pixel for 0dB, 7dB and 14dB attenuation conditions, and LV area obtained by summation of "LV cavity pixels". A reference LV cavity area was obtained from endocardial border tracings in enhanced scans by experts. RESULTS: Correlation of the HFR-defined and reference areas at systole was R=0.95, R=0.94, and R=0.91 for 0dB, 7dB and 14dB levels of attenuation, respectively, and at diastole was R=0.95 for 0dB, 7dB and 14dB levels of attenuation. The mean difference from both systolic and diastolic values was <1.45 cm(2) (i.e. negligible) in all attenuation settings. CONCLUSION: Our novel HFR method supports precise measurement of the LV cavity area in contrast images with simulated high attenuation of ultrasound signals. PMID- 17276475 TI - Sequence and annotation of the 288-kb ATCV-1 virus that infects an endosymbiotic chlorella strain of the heliozoon Acanthocystis turfacea. AB - Acanthocystis turfacea chlorella virus (ATCV-1), a prospective member of the family Phycodnaviridae, genus Chlorovirus, infects a unicellular, eukaryotic, chlorella-like green alga, Chlorella SAG 3.83, that is a symbiont in the heliozoon A. turfacea. The 288,047-bp ATCV-1 genome is the first virus to be sequenced that infects Chlorella SAG 3.83. ATCV-1 contains 329 putative protein encoding and 11 tRNA-encoding genes. The protein-encoding genes are almost evenly distributed on both strands and intergenic space is minimal. Thirty-four percent of the viral gene products resemble entries in the public databases, including some that are unexpected for a virus. For example, these unique gene products include ribonucleoside-triphosphate reductase, dTDP-d-glucose 4,6 dehydratase, potassium ion transporter, aquaglyceroporin, and mucin-desulfating sulfatase. Comparison of ATCV-1 protein-encoding genes with the prototype chlorella virus PBCV-1 indicates that about 80% of the ATCV-1 genes are present in PBCV-1. PMID- 17276477 TI - A host cell membrane protein, golgin-97, is essential for poxvirus morphogenesis. AB - Acquisition of the membrane and genome encapsidation is an important step in the replication of enveloped viruses. The biogenesis of the poxviral primary membrane and the core as well as the mechanisms of their maturation are poorly understood. Using RNA interference approach, we demonstrate that a cellular trans-Golgi network membrane protein, golgin-97, is essential for virus replication. Analysis of the virion morphology in the cells depleted of golgin-97 shows that the protein is required for the virus morphogenesis and, in particular, for the formation of the first infectious virus form, mature virus, but not its precursor, immature virus. This suggests that golgin-97 may be involved in the maturation of the virus core and, potentially, the virus membrane. PMID- 17276479 TI - The role of aluminum in slow sand filtration. AB - Engineering enhancement of slow sand filtration has been an enigma in large part because the mechanisms responsible for particle removal have not been well characterized. The presumed role of biological processes in the filter ripening process nearly precluded the possibility of enhancing filter performance since interventions to enhance biological activity would have required decreasing the quality of the influent water. In previous work, we documented that an acid soluble polymer controls filter performance. The new understanding that particle removal is controlled in large part by physical chemical mechanisms has expanded the possibilities of engineering slow sand filter performance. Herein, we explore the role of naturally occurring aluminum as a ripening agent for slow sand filters and the possibility of using a low dose of alum to improve filter performance or to ripen slow sand filters. PMID- 17276478 TI - The effect of biomass characteristics on the partitioning and sorption hysteresis of 17alpha-ethinylestradiol. AB - A membrane bioreactor (MBR) and a conventional bioreactor (CBR) were operated under various conditions to manipulate the biomass characteristics and evaluate the ensuing effects on the partitioning and sorption hysteresis of 17alpha ethinylestradiol (EE2). When the biomass was grown without nitrogen limitation, the biomass mean particle size had a dramatic effect on the observed partitioning coefficient (K(d)) and on sorption hysteresis index (HI). MBR K(d) (0.33-0.57L/g) values were equal to or larger than those of the CBR (0.25-0.33L/g). Under nitrogen-deficient conditions, the correlations between the biomass particle size and K(d) and HI were poor, likely because of extracellular polymeric substances. The K(d) and HI were determined for initial EE2 concentrations between 100 and 1000microg/L. Changing the SRT did not manipulate particle size, and the effects on K(d) and HI were not dramatic. This study also numerically explored the impacts of sorption hysteresis on the removal of pharmaceutical compounds. PMID- 17276476 TI - Human immunodeficiency virus-like particles activate multiple types of immune cells. AB - The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses. PMID- 17276480 TI - Copper desorption from Gelidium algal biomass. AB - Desorption of divalent copper from marine algae Gelidium sesquipedale, an algal waste (from agar extraction industry) and a composite material (the algal waste immobilized in polyacrylonitrile) was studied in a batch system. Copper ions were first adsorbed until saturation and then desorbed by HNO(3) and Na(2)EDTA solutions. Elution efficiency using HNO(3) increases as pH decreases. At pH=1, for a solid to liquid ratio S/L=4gl(-1), elution efficiency was 97%, 95% and 88%, the stoichiometric coefficient for the ionic exchange, 0.70+/-0.02, 0.73+/-0.05 and 0.76+/-0.06 and the selectivity coefficient, 0.93+/-0.07, 1.0+/-0.3 and 1.1+/ 0.3, respectively, for algae Gelidium, algal waste and composite material. Complexation of copper ions by EDTA occurs in a molar proportion of 1:1 and the elution efficiency increases with EDTA concentration. For concentrations of 1.4, 0.88 and 0.57 mmoll(-1), the elution efficiency for S/L=4gl(-1), was 91%, 86% and 78%, respectively, for algae Gelidium, algal waste and composite material. The S/L ratio, in the range 1-20gl(-1), has little influence on copper recovery by using 0.1M HNO(3). Desorption kinetics was very fast for all biosorbents. Kinetic data using HNO(3) as eluant were well described by the mass transfer model, considering the average metal concentration in the solid phase and the equilibrium relationship given by the mass action law. The homogeneous diffusion coefficient varied between 1.0 x 10(-7)cm(2)s(-1) for algae Gelidium and 3.0 x 10(-7)cm(2)s(-1) for the composite material. PMID- 17276481 TI - Sludge characteristics in anaerobic SBR system producing hydrogen gas. AB - In this study, sludge characteristics of anaerobic sequencing batch reactor (ASBR) were investigated to improve and optimize the efficiency of the system converting starch into biohydrogen. The effect of stratification in settling phase on H2-producing ASBR, which results in settleable and non-settleable sludge, was observed using a batch experiment. It was concluded that specific H2 activity of decanting non-settleable sludge was higher than that of settleable sludge, which may be the reason of low yield in H2-producing ASBR. In addition, effect of settling time on settleable sludge, which is another key operational parameter, was also analysed using another set of batch experiment. Settling time of the sludge was found to be an important parameter in H2-producing ASBR. Specific H2 activity varied inversely with the duration for which settleable microorganisms were contained in settling phase. Microbial species, responsible for H2 activity in each condition, were identified using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis. PMID- 17276482 TI - Anaerobic biodegradability and treatment of grey water in upflow anaerobic sludge blanket (UASB) reactor. AB - Feasibility of grey water treatment in an upflow anaerobic sludge blanket (UASB) reactor operated at different hydraulic retention time (HRT) of 16, 10 and 6h and controlled temperature of 30 degrees C was investigated. Moreover, the maximum anaerobic biodegradability without inoculum addition and maximum removal of chemical oxygen demand (COD) fractions in grey water were determined in batch experiments. High values of maximum anaerobic biodegradability (76%) and maximum COD removal in the UASB reactor (84%) were achieved. The results showed that the colloidal COD had the highest maximum anaerobic biodegradability (86%) and the suspended and dissolved COD had similar maximum anaerobic biodegradability of 70%. Furthermore, the results of the UASB reactor demonstrated that a total COD removal of 52-64% was obtained at HRT between 6 and 16 h. The UASB reactor removed 22-30% and 15-21% of total nitrogen and total phosphorous in the grey water, respectively, mainly due to the removal of particulate nutrients. The characteristics of the sludge in the UASB reactor confirmed that the reactor had a stable performance. The minimum sludge residence time and the maximum specific methanogenic activity of the sludge ranged between 27 and 93 days and 0.18 and 0.28 kg COD/(kg VS d). PMID- 17276483 TI - Experimental and statistical determination of indicator parameters for the evaluation of fly ash and boiler ash PCDD/PCDF concentration from municipal solid waste incinerators. AB - On-line detectable indicator parameters in the flue gas of municipal solid waste incinerators (MSWI) such as chlorinated benzenes (PCBz) are well known surrogate compounds for gas-phase PCDD/PCDF concentration. In the here presented work derivation of indicators is broadened to the detection of fly and boiler ash fractions with increased PCDD/PCDF content. Subsequently these fractions could be subject to further treatment such as recirculation in the combustion chamber to destroy their PCDD/PCDF and other organic pollutants' content. Aim of this work was to detect suitable on-line detectable indicator parameters in the gas phase, which are well correlated to PCDD/PCDF concentration in the solid residues. For this, solid residues and gas-phase samples were taken at three MSWI plants in Bavaria. Analysis of the ash content from different plants yielded a broad variation range of PCDD/PCDF concentrations especially after disturbed combustion conditions. Even during normal operation conditions significantly increased PCDD/PCDF concentrations may occur after unanticipated disturbances. Statistical evaluation of gas phase and ash measurements was carried out by means of principal component analysis, uni- and multivariate correlation analysis. Surprisingly, well known indicators for gas-phase PCDD/PCDF concentration such as polychlorinated benzenes and phenols proved to be insufficiently correlated to PCDD/PCDF content of the solid residues. Moreover, no single parameter alone was found appropriate to describe the PCDD/PCDF content of fly and boiler ashes. On the other hand, multivariate fitting of three or four parameters yielded convenient correlation coefficients of at least r=0.8 for every investigated case. Thereby, comprehension of plant operation parameters such as temperatures and air flow alongside concentrations of inorganic compounds in the gas phase (HCl, CO, SO2, NOx) gave the best results. However, the suitable set of parameters suited best for estimation of PCDD/PCDF concentration in solid residues has to be derived anew for each individual plant and type of ash. PMID- 17276484 TI - Heavy metal resistance and genotypic analysis of metal resistance genes in gram positive and gram-negative bacteria present in Ni-rich serpentine soil and in the rhizosphere of Alyssum murale. AB - Forty-six bacterial cultures, including one culture collection strain, thirty from the rhizosphere of Alyssum murale and fifteen from Ni-rich soil, were tested for their ability to tolerate arsenate, cadmium, chromium, zinc, mercury, lead, cobalt, copper, and nickel in their growth medium. The resistance patterns, expressed as minimum inhibitory concentrations, for all cultures to the nine different metal ions were surveyed by using the agar dilution method. A large number of the cultures were resistant to Ni (100%), Pb (100%), Zn (100%), Cu (98%), and Co (93%). However, 82, 71, 58 and 47% were sensitive to As, Hg, Cd and Cr(VI), respectively. All cultures had multiple metal-resistant, with heptametal resistance as the major pattern (28.8%). Five of the cultures (about of 11.2% of the total), specifically Arthrobacter rhombi AY509239, Clavibacter xyli AY509235, Microbacterium arabinogalactanolyticum AY509226, Rhizobium mongolense AY509209 and Variovorax paradoxus AY512828 were tolerant to nine different metals. The polymerase chain reaction in combination with DNA sequence analysis was used to investigate the genetic mechanism responsible for the metal resistance in some of these gram-positive and gram-negative bacteria that were, highly resistant to Hg, Zn, Cr and Ni. The czc, chr, ncc and mer genes that are responsible for resistance to Zn, Cr, Ni and Hg, respectively, were shown to be present in these bacteria by using PCR. In the case of, M. arabinogalactanolyticum AY509226 these genes were shown to have high homology to the czcD, chrB, nccA, and mer genes of Ralstonia metallidurans CH34. Therefore, Hg, Zn, Cr and Ni resistance genes are widely distributed in both gram-positive and gram-negative isolates obtained from A. murale rhizosphere and Ni-rich soils. PMID- 17276486 TI - Oily wastewater treatment using a novel hybrid PBR-UASB system. AB - In this study, anaerobic treatability of oily wastewater was investigated in a hybrid reactor system consisting of a packed bed reactor (PBR) followed by an upflow anaerobic sludge blanket (UASB) reactor at 35 degrees C. The system was operated using real pet food wastewater at different hydraulic retention times and loading rates for 165 d. The PBR was packed with sol-gel/alginate beads containing immobilized enzyme which hydrolyzed the oil and grease (O&G) into free long chain fatty acids, that were biodegraded by the UASB. The hybrid system was operated up to an oil loading rate of 4.9 kg O&Gm(-3)d(-1) (to the PBR) without any operational problems for a period of 100 d, with COD and O&G removal efficiencies above 90% and no sludge flotation was observed in the UASB. Beads supplement to the PBR was less than 2 g d(-1) and the relative activity was about 70%. Further increment in O&G loading to 18.7 kg O&Gm(-3)d(-1) caused destabilization of the system with 0.35% (v float/v feed) sludge float removed from the UASB. PMID- 17276485 TI - Induction and activity of oxidative stress-related proteins during waterborne Cd/Zn-exposure in brown trout (Salmo trutta). AB - We studied how transcript levels of metallothionein (MT), Cu/Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) as well as functional protein levels of MT, SOD and CAT in brown trout tissues changed during a 15-days waterborne exposure to Cd and Zn. Trout from a river with low levels of metals (the Stribekken River) was transferred to a river with high levels of Cd and Zn (the Naustebekken River) and exposed up to 15 days. The aim of this transfer experiment was to investigate how exposure to Cd and Zn induced transcription and activities of central antioxidant enzymes and proteins in an environmental setting. Significant uptake of both Cd and Zn was observed in gills during the 15 days exposure, and Cd levels was found to correlate significantly with transcript levels of MT-A, SOD, GPx and GR. Gill concentrations of Zn did not correlate significantly with the transcript levels of the stress genes studied, but Zn might have triggered transcription of proteins which dealt with subsequent accumulation of Cd. SOD and CAT activities increased in gills after transfer, but MT protein levels decreased. In liver, SOD activity and MT protein levels increased, while in kidney only MT protein concentrations were elevated after transfer. There was a general lack of consistency between mRNA transcription and enzyme activities, indicating that these proteins and enzymes are not solely under transcriptional control. PMID- 17276488 TI - Ultrasound and ozone assisted biological degradation of thermally pretreated and anaerobically pretreated distillery wastewater. AB - The present work is aimed at increasing the overall efficiency of the treatment process of distillery spent wash using a combination of different treatment techniques. Initially the effluent samples were subjected to Thermal Pretreatment (TPT-DW) and anaerobic treatment (ANA-DW). Advanced oxidation techniques, viz., Ultrasound (US) and Ozone were then used for further COD reduction followed by the conventional aerobic oxidation using mixed microbial consortium. Pretreatment of TPT-DW with US and Ozone (as stand alone techniques) enhanced the subsequent aerobic oxidation rate. For US treated sample, a maximum of 13% COD reduction was attained at the end of 48 h of aerobic oxidation, while for the ozone treated effluent a maximum of 45.6% COD reduction was obtained as compared to mere 1.8% COD reduction for the control (TPT-DW directly subjected to aerobic oxidation) indicating a 25 times increase in the rate of aerobic biodegradation of ozonated sample. Anaerobically treated effluent sample (ANA-DW) could be successfully treated aerobically. In this case, however, the use of advanced oxidation techniques did not result in any synergistic effects. The rate of the aerobic oxidation was slightly higher for the control (ANA-DW directly subjected to aerobic oxidation) as compared to the sample pretreated using ultrasound or ozonation. TOC analysis revealed that between the two pretreatments studied, ozone was found to be superior over US as it led to both COD as well as TOC reduction during the aerobic oxidation step for ANA-DW effluent stream. PMID- 17276487 TI - Preparation of coal slurry with organic solvents. AB - In this study, various organic solvents were used to prepare coal slurries and the rheological and thermal properties of coal-organic solvent slurries were examined. Solvents with molecules containing unpaired electrons (high basicity) show high extraction power and cause swelling of coal. Therefore, coal-organic solvent slurries usually showed higher viscosities compared to coal-water slurry. In addition, coal slurries prepared by alcohols and cyclohexanone demonstrated lower settling rates but a high specific sedimentation volume presumably because these solvents swelled coal particles well and led to the formation of weak gel structures in the bulk. In addition, ethanol and cyclohexanone are capable of breaking a considerable amount of hydrogen bonds in coal and subsequently opening up the structures. Thus, more surface area is available for combustion and the combustion rate of coal slurries was increased. PMID- 17276490 TI - Monometal and competitive adsorption of heavy metals by sewage sludge-amended soil. AB - Sewage sludge-amended soils may alter their ability to adsorb heavy metals over time, due to the decomposition of sludge-borne organic matter. Thus, we studied Cd, Ni, and Zn adsorption by a sewage sludge-amended soil (Typic Xerofluvent) before and after one-year incubation in both monometal and competitive systems. In the monometal system, the order of decreasing sorption was Zn>Cd>Ni. Competition significantly reduced metal K(d), especially that of Cd which decreased by nearly 50%. Over the course of the incubation there was a 31% reduction of soil organic matter content. At the same time, in competitive systems Cd K(d) significantly decreased, while Zn K(d) significantly increased, and Ni K(d) remained unaffected. This study shows that sewage sludge-amended soils may change in their ability to sorb heavy metals over time at high metal concentrations. The data suggest that Cd is likely to be of most environmental significance in such soils, since it exhibited decreased sorption under competitive conditions and as the organic matter content of the soil was reduced. The potential for long-term release of metals should be considered in the risk assessment associated with sewage sludge addition to soils, particularly in climates where degradation of organic matter is likely to be enhanced. PMID- 17276489 TI - Changes in PCDD/PCDF formation processes during instationary phases of combustor operation--exemplified by the use of Cl4DD isomer patterns. AB - In this paper results of various measurement campaigns at different municipal waste incineration (MWI) plants concerning the change of the PCDD/PCDF isomer distribution in the crude gas during transiently impaired combustion conditions are presented. The focus is on the Cl4DD isomer distributions exemplarily for all other homologue groups to demonstrate the change in PCDD/PCDF formation mechanism at transient combustion conditions. Additionally to crude gas samples, at one plant filter and boiler ash were investigated simultaneously to determine if there is any difference in the isomer distribution between the matrices. For the ash from an electrostatic precipitator (ESP ash), the boiler ash and the corresponding crude gas sample, nearly identical changes in the Cl4DD isomer distribution under transient combustion conditions in relation to the normal operation process could be detected. By comparing the Cl4DD isomer distributions from different incineration plants (two municipal waste incinerators and one little incinerator burning wood chips for heating domestic household) under transient combustion conditions, in all cases the 1,3,6,8- and 1,3,7,9-Cl4DD were dominating the isomer distribution, whereas under normal operation other isomers were predominant. Obviously PCDD/PCDF formation mechanisms under transient combustion conditions are independent from the type of incinerator and of the burned fuel, respectively. Data sets were analyzed with respect to the possible reaction mechanism via chlorophenols and a good correlation of 2,4,6 trichlorophenol during the second phase of a start-up process and during a CO experiment was found. To get more detailed information about possible formation mechanisms, at one plant the dependence of the PCDD/PCDF isomer distribution on the different matrices was studied. Separate analysis of fly ash collected at the boiler exit, subsequent gas phase, ESP ash and boiler ash under normal operation conditions showed that, apart from the fly ash, the Cl4DD isomer distributions are nearly the same in the different matrices. Surprisingly, the Cl4DD isomer distribution of the fly ash was more similar to the distributions found under transient combustion conditions. PMID- 17276491 TI - Recommendations for the reporting of pleural mesothelioma. AB - It has been evident for decades that pathology reports are very variable even within a single institution. Standardization of reporting is the optimal way to ensure that information necessary for patient management, prognostic and predictive factor assessment, grading, staging, analysis of outcomes, and tumor registries is included in pathology reports. In recent years, 2 societies (first the Association of Directors of Anatomic and Surgical Pathology [ADASP] and then the College of American Pathologists [CAP]) have undertaken to publish guidelines for the reporting of common cancers. The CAP assigned multidisciplinary groups of pathologists, surgeons, radiation, and medical oncologists to develop the protocols. Other pathologists and clinicians then reviewed them. After those reviews the protocols were reviewed by multiple CAP committees and finally approved by the Board of Governors. The ADASP, in contrast, chose a pathologist expert in each filed to assemble a group from within the pathology community (with clinician input if desired) to write specific cancer protocols. These were then approved by the ADASP council and subsequently by the membership. Although both societies began the process at approximately the same time, the streamlined approach adopted by the ADASP enabled them to publish years earlier in pathology journals frequented by anatomic pathologists. Although the formats are somewhat different, the contents are essentially the same. The American College of Surgery Commission on Cancer (COC) accredits cancer centers in the United States. Recently, the COC decided to require elements, deemed as essential by the CAP, to be described in all pathology reports in their accredited cancer centers as of January 2004. Importantly, they do not require that the specific CAP protocols or synoptic reports be used. The ADASP has updated all of its protocols to comply with the COC requirements in the form of 37 uniform checklists. The checklists use the staging criteria sited in the American Joint Committee on Cancer 2002 Staging Manual (sixth edition) but include a variety of other references listed in each of the checklists. Moreover, the checklists are formatted for ease of use. They may be used as templates for uniform reporting and are designed to be compatible with voice-activated transcription. The different elements in these revised ADASP diagnostic checklists have been divided into required and optional. The term required in this context only signifies compliance with the COC guidelines. The ADASP realizes that specimens and practices vary, and it will not be possible to report these elements in every case. However, the ADASP hopes that pathologists will find these checklists to be useful in daily clinical practice, while facilitating compliance with the new COC requirements. PMID- 17276492 TI - Release of copper from sintered tungsten-bronze shot under different pH conditions and its potential toxicity to aquatic organisms. AB - Sintered tungsten-bronze is a new substitute for lead shot, and is about to be deposited in and around the wetlands of North America. This material contains copper in the alloyed form of bronze. This in vitro study was performed according to U.S. Fish and Wildlife Service criteria to determine the dissolution rate of copper from the shot, and to assess the toxic risk that it may present to aquatic organisms. The dissolution of copper from tungsten-bronze shot, pure copper shot, and glass beads was measured in a buffered, moderately hard, synthetic water of pH 5.5, 6.6, and 7.8 over a 28-day period. The dissolution of copper from both the control copper shot and the tungsten-bronze shot was affected significantly by the pH of the water and the duration of dissolution (all p values<0.000). The rate of copper release from tungsten bronze shot was 30 to 50 times lower than that from the copper shot, depending on pH (p<0.0000). The observed expected environmental concentration of copper released from tungsten-bronze shot after 28 days was 0.02 microg/L at pH 7.8, and 0.4 microg/L at pH 5.6, using a loading and exposure scenario specific in a U.S. Fish and Wildlife Service protocol. Ratio Quotient values derived from the highest EEC observed in this study (0.4 microg/L), and the copper toxic effect levels for all aquatic species listed in the U.S. Environmental Protection Agency ambient water quality criteria database, were all far less than the 0.1 criterion value. Given the conditions stipulated by the U.S. Fish and Wildlife Service and the U.S. Environmental Protection Agency, heavy loading from discharged tungsten-bronze shot would not pose a toxic risk to potable water, or to soil. Consequently, it would appear that no toxic risks to aquatic organisms will attend the use of tungsten-bronze shot of the approved composition. Given the likelihood that sintered tungsten-bronze of the same formula will be used for fishing weights, bullets, and wheel balance weights, it is expected that the use of this new material in these applications will not be associated with toxic risks to aquatic life. PMID- 17276493 TI - Using genetic algorithms to calibrate a water quality model. AB - With the increasing concern over the impact of diffuse pollution on water bodies, many diffuse pollution models have been developed in the last two decades. A common obstacle in using such models is how to determine the values of the model parameters. This is especially true when a model has a large number of parameters, which makes a full range of calibration expensive in terms of computing time. Compared with conventional optimisation approaches, soft computing techniques often have a faster convergence speed and are more efficient for global optimum searches. This paper presents an attempt to calibrate a diffuse pollution model using a genetic algorithm (GA). Designed to simulate the export of phosphorus from diffuse sources (agricultural land) and point sources (human), the Phosphorus Indicators Tool (PIT) version 1.1, on which this paper is based, consisted of 78 parameters. Previous studies have indicated the difficulty of full range model calibration due to the number of parameters involved. In this paper, a GA was employed to carry out the model calibration in which all parameters were involved. A sensitivity analysis was also performed to investigate the impact of operators in the GA on its effectiveness in optimum searching. The calibration yielded satisfactory results and required reasonable computing time. The application of the PIT model to the Windrush catchment with optimum parameter values was demonstrated. The annual P loss was predicted as 4.4 kg P/ha/yr, which showed a good fitness to the observed value. PMID- 17276494 TI - Changes in organic matter and residual effect of amendment with two-phase olive mill waste on degraded agricultural soils. AB - Agricultural soils from many parts of the Mediterranean region are very poor in organic matter and are exposed to progressive degradation processes. Therefore, additions of the olive-mill waste from a continuous two-phase system as an organic amendment can improve soil quality and hence mitigate the negative environmental and agronomic limitations of these soils. A field study under semiarid Mediterranean conditions was conducted to evaluate the changes in organic matter after four consecutive annual additions of olive-mill watery husk (OMWH) waste and the de-oiled two-phase olive pomace (TPOP) waste on an olive grove soil: a cutanic Luvisol (CL). Treatments included a control, OMWH (30 and 60 Mg ha(-1), DW equivalent), and TPOP (27 and 54 Mg ha(-1), DW equivalent). Also, a two-year greenhouse study using wheat (Triticum aestivum L.) was conducted to evaluate the residual effects of adding OMWH to CL soil and to a degraded Leptic Cambisol (LC). Treatments included five OMWH rates ranging from 0 to 40 Mg ha(-1). Significant increases in total organic carbon (TOC), water soluble organic carbon (WSOC), humic and fulvic acids, and aggregate stability were observed in the treated plots, and the highest humification index was obtained when OMWH was applied at the lowest rate. The increase in aggregate stability correlated positively and highly significantly (P<0.01) with the humic and fulvic acid and WSOC contents. In the greenhouse, significant increases in TOC, carbohydrates, aggregate stability, total N, available K, and cation exchange capacity were observed in both soils. However, available P decreased significantly. There was an increased residual fertilization effect of OMWH for both soils. The best fits to grain yield and OMWH rates were with a linear regression for the CL soil (R(2)=0.957 and P<0.01), and a quadratic regression for the LC soil (R(2)=0.960 and P<0.01). PMID- 17276495 TI - Dissolved and bioavailable contaminants in the Seine river basin. AB - Diffusive Gradient in Thin Films (DGT) and Semi-Permeable Membrane Devices (SPMDs) were deployed in the Seine river basin in order to assess labile metals and truly dissolved Polycyclic Aromatic Hydrocarbons. We show that the tools are reliable in aquatic environments to assess the speciation of dissolved contaminants and hence provide a good insight into the potential bioavailability of contaminants. The deployment of the DGT and SPMDs in contrasting environments in the Seine river basin allowed distinction to be made of availability of contaminants between headwater streams and much more impacted river reaches and an assessment of bioavailability. At the stations under urban influence, the impact of dissolved organic matter on both copper and PAHs bioavailability is less pronounced than at upstream stations, where humic substances dominate. PMID- 17276496 TI - MEFV mutations in Tunisian patients suffering from familial Mediterranean fever. AB - OBJECTIVES: To identify the frequency and distribution of familial Mediterranean fever (FMF) gene (MEFV) mutations in Tunisian patients. PATIENTS AND METHODS: This study was performed in the Genetic Department of Tunis University Hospital. A clinical diagnosis of FMF was made according to published criteria. Mutation screening of the MEFV gene was performed in the Human Genetic Laboratory of the "Faculte de Medecine de Tunis" for 8 mutations including the 5 most common known mutations M694V, V726A, M694l, M680l, and E148Q. The tests performed were polymerase chain reaction (PCR) restriction-digestion for M694V, V726A, M680l, R761H, E148Q; amplification refractory mutation system for A744S, M694l; and PCR electrophoresis assay for l692del. RESULTS: Of the 139 unrelated patients investigated, 61 (44%) had 1 or 2 mutations. In 78 (56%) probands no mutation was identified: 28 patients were homozygous; 16 were compound-heterozygous; 2 had complex alleles; and 17 had only 1 identifiable mutation. Of the mutations, M680l, M694V, M694l, V726A, A744S, R761H, l692DEL, and E148Q accounted for 32, 27, 13, 5, 3, 1, 1, and 18%, respectively. CONCLUSION: The profile of the MEFV gene mutations in the Tunisian population is concordant with other Arab populations but with some differences. M680l is the most common mutation, while V726A, the commonest mutation among Arabs, is rare in our population. PMID- 17276497 TI - How common are connective tissue disorders in patients with autoimmune hepatitis? PMID- 17276498 TI - Exploring the cause of the most ancient clinical sign of medicine: finger clubbing. AB - OBJECTIVE: Digital clubbing is regarded as the oldest clinical sign of medicine. The cause of this unique finger deformity has remained elusive throughout the centuries. For 3 decades our group has studied the etiology of this acropachy. This article reviews the current knowledge on the cause of digital clubbing. METHODS: PubMed database (www.pubmed.gov) was accessed. In clinical queries/clinical study service we entered "clubbing" or "hypertrophic osteoarthropathy," choosing the "etiology" category with a "broad sensitive" search scope. The time span was from January 1975 to August 2006. Additionally, this article narrates the chronology of our research on the pathogenesis of clubbing. RESULTS: The many dreadful internal illnesses associated with digital clubbing have in common enhanced platelet/endothelial cell activation. Emerging evidence suggests that, in hypoxic conditions with extrapulmonary shunting of blood, large megakaryocyte fragments fail to enter the pulmonary circulation. Instead they gain access to the systemic circulation impacting at the most distal sites, there releasing growth factors and thus inducing clubbing. In cases of lung cancer, the purported growth factor could gain direct entrance to the systemic circulation. Vascular endothelial growth factor (VEGF) may play a central role in the development of digital clubbing. It is a platelet-derived factor induced by hypoxia, and it is also abnormally produced by diverse malignant tumors fostering their uncontrolled growth. On the other hand VEGF produces vascular hyperplasia, edema, and fibroblast/osteoblast proliferation. Such are clubbing histologic characteristics. Enhanced VEGF expression has been reported in practically all internal illnesses associated with this type of finger deformity. Recent studies have demonstrated high circulating levels as well as increased local expression of VEGF in different groups of patients with digital clubbing. CONCLUSION: Abnormal expression of VEGF may be the cause of digital clubbing. PMID- 17276499 TI - Abnormalities of homocysteine and B vitamins in the nephrotic syndrome. AB - INTRODUCTION: The nephrotic syndrome is associated with heightened risk for arterial and venous thrombosis. Multiple derangements of hemostasis and acquired risk factors such as hyperlipidemia and hypertension contribute to this risk. The prevalence in the nephrotic syndrome of high circulating levels of homocysteine and of low levels of the B vitamins that are involved in its metabolism, which may play a role in thrombosis, is not well defined. MATERIALS AND METHODS: In 84 patients with nephrotic syndrome and 84 sex- and age-matched controls, hemostasis variables and the circulating levels of total homocysteine (tHcy), vitamin B(6), B(12) and folates were measured. RESULTS: tHcy levels were higher, vitamin B(6) and vitamin B(12) levels were lower in nephrotic patients than in controls. The association of low vitamin B(6) levels with the nephrotic syndrome was independent of any other alteration associated with the disease. Eighty-two percent of patients with the nephrotic syndrome had vitamin B(6) levels falling in the lowest quartile of the normal distribution. Antithrombin deficiency, factor V Leiden, antiphospholipid antibodies, hypertension, dyslipidemia, were more frequent in patients with the nephrotic syndrome than in controls. CONCLUSIONS: Patients with the nephrotic syndrome have multiple risk factors for thrombosis. We report that they frequently have low circulating levels of vitamin B(6), which associate with a heightened risk for venous and arterial thrombosis. PMID- 17276500 TI - Regulation of the metastasis suppressor gene MKK4 in ovarian cancer. AB - OBJECTIVES: MKK4 is a metastasis suppressor that is downregulated in some ovarian cancers. We sought to investigate whether promoter methylation, loss of heterozygosity, or changes in phosphorylation are involved in MKK4 dysregulation during ovarian carcinogenesis. METHODS: Bisulfite sequencing was used to determine MKK4 promoter methylation. PCR analysis of tumor/normal DNA was performed to determine LOH at the MKK4 locus. Normal human ovarian surface epithelium (HOSE) and SKOV-3 cells were serum starved and treated with EGF, TGFbeta, or wortmannin. Western blotting was performed using antibodies that detect total and phosphorylated MKK4. RESULTS: No MKK4 promoter hypermethylation was detected in 21 ovarian cancers. LOH was detected at the MKK4 intragenic marker D17S969 in 35% of cases and at D17S1303 in 20%. MKK4 protein was detected in 97% of ovarian tumors. The inactivated phosphoserine 80 (ser-80) form comprised 62% of phosphorylated MKK4 protein in ovarian tumors. Treatment of HOSE or SKOV-3 cells with EGF induced a 1.7- to 4.2-fold increase in phosphorylation of ser-80 MKK4 without altering total MKK4 protein. TGFbeta increased MKK4 ser-80 phosphorylation by 5.4-fold above baseline. The PI3K/Akt pathway inhibitor wortmannin decreased the amount of ser-80 MKK4 by 50%, and inhibited EGF stimulation of MKK4 ser-80 phosphorylation by 60%. CONCLUSIONS: LOH of MKK4 occurs in some ovarian cancers, but without loss of MKK4 protein. MKK4 expression does not appear to be downregulated by promoter methylation. Peptide growth factors induce MKK4 ser-80 phosphorylation, which downregulates its activity. PI3K/Akt pathway inhibitors can partially block ser-80 phosphorylation and this may have therapeutic implications. PMID- 17276502 TI - Understanding the intricate network of signaling molecules. PMID- 17276503 TI - Comparative quantitative assessment of GnRH- and LH-receptor mRNA expression in the urinary tract of sexually intact and spayed female dogs. AB - Ovariectomy interrupts the regulatory loop in the hypothalamus-pituitary-gonad axis, leading to a several-fold increase in gonadotropin levels. This rise in hormonal secretion may play a causal role in ovariectomy-related urinary incontinence. The purpose of this study was to examine the effect of ovariectomy in bitches on the expression of GnRH- and LH-receptors in the lower urinary tract, and assess the relationship between receptor expression and plasma gonadotropin concentrations. Plasma gonadotropins were measured in 37 client owned bitches. Biopsies were harvested from the mid-ventral bladder wall in all dogs, and from nine further locations within the lower urinary tract in 17 of the 37 animals. Messenger RNA of the LH and GnRH receptors was quantified using RT PCR with the TaqMan Universal PCR Master Mix. Gonadotropins were measured with a canine-specific FSH-immunoradiometric assay and LH-radioimmunoassay. The hierarchical mixed ANOVA model using MINITAB, Mann-Whitney U-test, unpaired means comparison and linear regressions using StatView were applied for statistical analyses. Messenger RNA for both receptors was detected in all biopsy samples. Age was negatively correlated to mRNA expression of the LH and the GnRH receptors. A relationship between the mRNA values and the plasma gonadotropin concentrations was not established. Evaluation of results within each of the biopsy locations revealed greater LH-receptor expression in the proximal second quarter of the urethra in spayed bitches than in intact bitches (P=0.0481). Increased mRNA expression of LH receptors in this location could possibly play a role in the decrease in closing pressure of the urethra following ovariectomy. PMID- 17276501 TI - Anticancer and chemosensitizing effects of 2,3-DCPE in ovarian carcinoma cell lines: link with ERK activation and modulation of p21WAF1/CIP1, Bcl-2 and Bcl-xL expression. AB - OBJECTIVE: Emergence of chemoresistance in the course of treatments with platinum drugs remains a major hurdle to ovarian carcinoma therapy. We have previously shown that acquisition of cisplatin resistance by OAW42-R ovarian carcinoma cells was associated with the loss of ERK activation in response to cisplatin. To try to sensitize this cell line by restoring ERK activation, we tested a new synthetic compound, 2[[3-(2,3-dichlorophenoxy)propyl]amino]ethanol (2,3-DCPE), which was described to induce ERK activation and to display anticancer properties. METHODS: We treated four ovarian carcinoma cell lines with 2,3-DCPE, alone or combined with cisplatin. We characterized its effects on apoptosis induction and proliferation and correlated them with molecular modulations. RESULTS: We showed that 2,3-DCPE induced cell death and ERK phosphorylation in a time- and concentration-dependent manner in OAW42-R cells. 2,3-DCPE-triggered apoptosis was also associated with the inhibition of Bcl-2 expression and, to a less extent, with that of Bcl-xL. Treatment with 2,3-DCPE also elicited a strong G0/G1 cell cycle arrest, accompanied with p21WAF1/CIP1 up-regulation. All of these effects revealed to be irreversible. Moreover, 2,3-DCPE exerted a cytostatic effect on OAW42, IGROV1-R10 and SKOV3 ovarian carcinoma cells, the sensitivity to 2,3-DCPE appearing in particular linked with a low basal level of P-ERK. Finally, we showed that 2,3-DCPE increased the cytotoxic effect of cisplatin in OAW42-R resistant cells. CONCLUSION: Our results emphasized the potential interest of 2,3-DCPE, used alone or combined with cisplatin, for ovarian carcinoma treatment. The absence of basal P-ERK may constitute a predictive marker of response to this novel therapy. PMID- 17276505 TI - Seasonal variability of denitrification efficiency in northern salt marshes: an example from the St. Lawrence Estuary. AB - In coastal ecosystems, denitrification is a key process in removing excess dissolved nitrogen oxides and participating in the control of eutrophication process. Little is known about the role of salt marshes on nitrogen budgets in cold weather coastal areas. Although coastal salt marshes are important sites for organic matter degradation and nutrient regeneration, bacterial-mediated nitrogen cycling processes, such as denitrification, remain unknown in northern and sub arctic regions, especially under winter conditions. Using labelled nitrogen (15N), denitrification rates were measured in an eastern Canadian salt marsh in August, October and December 2005. Freshly sampled undisturbed sediment cores were incubated over 8h and maintained at their sampling temperatures to evaluate the influence of low temperatures on the denitrification rate. From 2 to 12 degrees C, average denitrification rate and dissolved oxygen consumption increased from 9.6 to 25.5 micromol N2 m-2 h-1 and from 1.3 to 1.8 mmol O2 m-2 h 1, respectively, with no statistical dependence of temperature (p>0.05). Nitrification has been identified as the major nitrate source for denitrification, supplying more than 80% of the nitrate demand. Because no more than 31% of the nitrate removed by sediment is estimated to be denitrified, the presence of a major nitrate sink in sediment is suspected. Among possible nitrate consumption mechanisms, dissimilatory reduction of nitrate to ammonium, metal and organic matter oxidation processes are discussed. Providing the first measurements of denitrification rate in a St. Lawrence Estuary salt marsh, this study evidences the necessity of preserving and restoring marshes. They constitute an efficient geochemical filter against an excess of nitrate dispersion to coastal waters even under cold northern conditions. PMID- 17276504 TI - Genetic studies of stuttering in a founder population. AB - Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions with nominal evidence for linkage were found on chromosomes 3 (P=0.013, 208.8 centiMorgans (cM)), 13 (P=0.012, 52.6 cM), and 15 (P=0.02, 100 cM). Regions with nominal evidence for association with stuttering that overlapped with a linkage signal are located on chromosomes 3 (P=0.0047, 195 cM), 9 (P=0.0067, 46.5 cM), and 13 (P=0.0055, 52.6 cM). We also conducted the first meta-analysis for stuttering using results from linkage studies in the Hutterites and The Illinois International Genetics of Stuttering Project and identified regions with nominal evidence for linkage on chromosomes 2 (P=0.013, 180-195 cM) and 5 (P=0.0051, 105-120 cM; P=0.015, 120-135 cM). None of the linkage signals detected in the Hutterite sample alone, or in the meta analysis, meet genome-wide criteria for significance, although some of the stronger signals overlap linkage mapping signals previously reported for other speech and language disorders. EDUCATIONAL OBJECTIVES: After reading this article, the reader will be able to: (1) summarize information about the background of common disorders and methodology of genetic studies; (2) evaluate the role of genetics in stuttering; (3) discuss the value of using founder populations in genetic studies; (4) articulate the importance of combining several studies in a meta-analysis; (5) discuss the overlap of genetic signals identified in stuttering with other speech and language disorders. PMID- 17276506 TI - Retroviral microarray-based platform on nanostructured TiO2 for functional genomics and drug discovery. AB - Living-cell microarrays are powerful tools for functional genomics and drug discovery. However, despite several attempts to improve this technology, it is still a challenge to obtain microarrays of cells efficiently overexpressing or downregulating specific genes to address complex phenotypes. Here, we present a cell-based microarray for phenotype screening on primary and cancer cells based on the localized reverse infection by retroviruses. Viral vectors are immobilized on a nanostructured titanium dioxide (ns-TiO2) film obtained by depositing a supersonic beam of titania clusters on a glass substrate. We validated the retroviral cell array by overexpression of GFP reporter genes in primary and cancer cells, and by RNA interference of p53 in primary cells by analyzing effects in cell growth. We demonstrate that ns-TiO2 retroviral arrays are an enabling tool for the study of gene function of families of genes for complex phenotypes and for the identification of novel drug targets. PMID- 17276507 TI - Biodegradable magnesium-hydroxyapatite metal matrix composites. AB - Recent studies indicate that there is a high demand to design magnesium alloys with adjustable corrosion rates and suitable mechanical properties. An approach to this challenge might be the application of metal matrix composite (MMC) based on magnesium alloys. In this study, a MMC made of magnesium alloy AZ91D as a matrix and hydroxyapatite (HA) particles as reinforcements have been investigated in vitro for mechanical, corrosive and cytocompatible properties. The mechanical properties of the MMC-HA were adjustable by the choice of HA particle size and distribution. Corrosion tests revealed that HA particles stabilised the corrosion rate and exhibited more uniform corrosion attack in artificial sea water and cell solutions. The phase identification showed that all samples contained hcp-Mg, Mg(17)Al(12), and HA before and after immersion. After immersion in artificial sea water CaCO3 was found on MMC-HA surfaces, while no formation of CaCO3 was found after immersion in cell solutions with and without proteins. Co-cultivation of MMC-HA with human bone derived cells (HBDC), cells of an osteoblasts lineage (MG-63) and cells of a macrophage lineage (RAW264.7) revealed that RAW264.7, MG 63 and HBDC adhere, proliferate and survive on the corroding surfaces of MMC-HA. In summary, biodegradable MMC-HA are cytocompatible biomaterials with adjustable mechanical and corrosive properties. PMID- 17276508 TI - Role of dorsal vagal motor nucleus orexin-receptor-1 in glycemic responses to acute versus repeated insulin administration. AB - The potent orexigenic neuropeptide, orexin-A (ORX-A), acts at multiple sites within the central neuroaxis to control autonomic responses to energy imbalance, including the dorsal vagal motor nucleus (DMV), where it regulates pancreatic efferent nerve firing. Recent evidence that recurrent insulin-induced hypoglycemia (RIIH) attenuates lateral hypothalamic ORX-A-ergic neuronal transcriptional activation and prepro-orexin gene expression suggests that this phenotype undergoes functional adaptation to repeated glucoprivation. We examined the hypothesis that RIIH-associated patterns of ORX-A neurotransmission and/or orexin-receptor-1 (OR-1) expression within the DMV may be correlated with exacerbated hypoglycemic and impaired pancreatic counterregulatory responses to repeated insulin administration. Male rats were pretreated by bilateral intra-DMV infusion of the OR-1 antagonist, SB-334867, or vehicle prior to s.c. injection of Humulin NPH (NPH), or diluent alone. Other animals were injected with one or four doses of NPH, on as many days, or diluent alone, and pretreated by bilateral intra-DMV administration of graded doses of ORX-A or vehicle on the final day of the study. Effects of acute versus repeated insulin administration on ORX-A and OR-1 protein levels in the microdissected dorsal vagal complex (DVC) were evaluated by radioimmunoassay and Western blot analyses, respectively. SB-334867 treatment prior to acute NPH administration decreased plasma glucose and suppressed peak glucagon secretion, whereas exogenous ORX-A administration prior to RIIH did not reverse amplified patterns of hypoglycemia. RIIH did not alter intra-DVC ORX-A tissue concentrations, but diminished OR-1 levels in that site. These results show that DMV OR-1 function is critical for optimal glucagon secretory responsiveness to acute hypoglycemia, and that RIIH-associated downregulation of receptor expression in that brain site may contribute to impaired restoration of euglycemia. The current data provide unique evidence that ORX-A acts via OR-1-dependent mechanisms within DMV to regulate glucagon counterregulatory function during hypoglycemia, and that decreased receptor mediated signaling during RIIH may underlie characteristic intensification of hypoglycemia. PMID- 17276509 TI - Blockade of neurotensin receptors during amphetamine discontinuation indicates individual variability. AB - Psychostimulant-induced locomotor sensitization has been related to changes within the mesolimbic dopamine system and has been suggested to be useful to study mechanisms underlying drug craving. Neurotensin is a neuropeptide co localized with dopamine in the mesolimbic system. The response to novelty has been suggested to be a predictor of enhanced vulnerability to behavioral sensitization. The effects of repeated treatment with the neurotensin antagonist SR48692 after amphetamine discontinuation were investigated in mice previously classified as high responders (HRs) or low responders (LRs) to novelty. Mice were repeatedly treated with 2.0mg/kg amphetamine, every other day for 11 days. During the first 7 days after amphetamine discontinuation, the animals received a daily injection of saline or 0.3mg/kg SR48692. On the eighth day after amphetamine discontinuation all subjects received a 2.0mg/kg amphetamine challenge injection. Then, mice were tested for an open field behavior and after 90min, were sacrificed for Fos expression quantification in the nucleus accumbens. Both HRs and LRs expressed amphetamine-induced sensitized locomotor activation and increased expression of Fos protein. Treatment with SR48692 prevented behavioral sensitization and Fos protein expression enhancement in LRs but not in HRs mice. These data suggest that neurotensin plays a role in individual variability to amphetamine-induced sensitization. PMID- 17276510 TI - Activities of cellulase and amylase in soils as influenced by insecticide interactions. AB - Interaction effects of the insecticides monocrotophos and quinalphos (organophosphates), and cypermethrin (pyrethroid), on microbial activities in two agricultural soils-black vertisol soil and red alfinsol soil were tested for 30 days under laboratory conditions. Individual application of the three insecticides at 5, 10 and 25microg g(-1) to the soil distinctly enhanced the activities of cellulase and amylase. Insecticide combinations involving monocrotophos or quinalphos with cypermethrin yielded synergistic, antagonistic and additive interaction effects on both enzymes in the soils. At lower levels, 5 and 10microg g(-1), the insecticides in combination interacted additively or synergistically toward both enzymes. But, both combinations at the highest level of 25microg g(-1) exhibited an antagonistic interaction, with a reduction in enzyme activities to a level lower than that of the control. Interaction effects of insecticides in combinations on two enzyme activities in both soils were related to populations of cellulolytic and amylolytic organisms in soils under the impact of combination of insecticides. These interaction responses were persistent even for 30 days. PMID- 17276512 TI - Patients' attitudes to Helicobacter pylori breath and stool antigen tests compared to blood serology. AB - BACKGROUND: The National Institute for Health and Clinical Excellence (NICE) recommends that patients with uninvestigated dyspepsia, unresponsive to proton pump inhibitors, should be tested for Helicobacter pylori using a stool antigen or urea breath test rather than blood-based serology. OBJECTIVE: To determine if a stool antigen or urea breath test is acceptable to patients. METHOD: Satisfaction questionnaire circulated to all primary care patients who had blood serology for H. pylori between January and July 2004. RESULTS: Four hundred and sixty-two out of 717 Gloucestershire patients returned the questionnaire. Three quarters of respondents stated that they would be willing to provide a stool or breath H. pylori test if they were told they were more accurate than the blood test. If the blood test was not available, 58% stated they would prefer the breath test and 34% the stool test. When patients were not given an explanation for the transfer to the new tests, only 11% stated they would prefer to provide a stool and 19% the breath test. 80% required an extra appointment for their blood test. CONCLUSION: The majority of patients would be happy to provide a stool sample or breath test provided they are made aware that these tests are more accurate than blood serology. PMID- 17276511 TI - Synthesis and pharmacochemical study of new Cu(II) complexes with thiophen-2-yl saturated and alpha,beta-unsaturated substituted carboxylic acids. AB - Copper complexes with thiophen-2-yl saturated and alpha,beta-unsaturated carboxylic acids as ligands were prepared, characterized and pharmacochemically studied. The available evidence supports a dimeric structure for the complexes of the general formula [Cu2(L)4(MeOH)2] where L are the anions of thiophene 2 carboxylic acid (HL1), 2-(thiophen-2-yl)-acetic acid (HL2), 3-thiophen-2-yl acrylic acid (HL3), 2-phenyl-3-thiophen-2-yl-acrylic acid (HL4) respectively. The crystal structure of [Cu2(L1)4(MeOH)2] (2) was determined while preliminary X-ray analysis of the copper complex with L4 isolated from MeOH/DMSO solution proved to contain three crystallographically independent dimers of the formula [Cu2(L4)4(MeOH)(dmso)][Cu2(L4)4(MeOH)2][Cu2(L4)4(dmso)2].8MeOH (9). Since lipophilicity is a significant physicochemical property determining distribution, bioavailability, metabolic activity and elimination, we tried to measure experimentally their lipophilicity from RPTLC method. The copper complexes and the ligands (thiophen-2-yl saturated and alpha,beta-unsaturated carboxylic acids) were tested in vitro on: (a) soybean lipoxygenase inhibition, (b) interaction with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, (c) the HO* mediated oxidation of DMSO, (d) inhibition of lipid peroxidation, (e) scavenging of superoxide anion radicals and in vivo for the inhibition of carrageenin induced rat paw edema. The compounds have shown important antioxidant activity, significant anti-inflammatory activity and potent inhibition of soybean lipoxygenase as a result of their physichochemical features. Complex [Cu2(L1)4(MeOH)2] (2) presents the higher in vivo activity (77.4%) followed by complex [Cu2(L2)4(MeOH)2] (4) (51%). Both complexes are more potent anti inflammatory agents compared to their respective ligands. Moreover we have performed in vitro studies upon their effect on dsDNA, using adsorptive transfer stripping voltammetry and a dsDNA modified carbon paste electrode. Our conclusions were mainly based upon the effect of the studied compounds on the oxidation signal of guanine and adenine. From the given data it seems that complexes show similarities in their behaviour. PMID- 17276513 TI - Differentiating major depressive disorder in youths with attention deficit hyperactivity disorder. AB - BACKGROUND: Youths with attention deficit hyperactivity disorders (ADHD) frequently have comorbid major depressive disorders (MDD) sharing overlapping symptoms. Our objective was to examine which depressive symptoms best discriminate MDD among youths with ADHD. METHODS: One-hundred-eleven youths with ADHD (5.2-17.8 years old) and their parents completed interviews with the K-SADS PL and respective versions of the child or the parent Mood and Feelings Questionnaire (MFQ-C, MFQ-P). Controlling for group differences, logistic regression was used to calculate odds ratios reflecting the accuracy with which various depressive symptoms on the MFQ-C or MFQ-P discriminated MDD. Stepwise logistic regression then identified depressive symptoms that best discriminated the groups with and without MDD, using cross-validated misclassification rate as the criterion. RESULTS: Symptoms that discriminated youths with MDD (n=18) from those without MDD (n=93) were 4 of 6 mood/anhedonia symptoms, all 14 depressed cognition symptoms, and only 3 of 11 physical/vegetative symptoms. Mild irritability, miserable/unhappy moods, and symptoms related to sleep, appetite, energy levels and concentration did not discriminate MDD. A stepwise logistic regression correctly classified 89% of the comorbid MDD subjects, with only age, anhedonia at school, thoughts about killing self, thoughts that bad things would happen, and talking more slowly remaining in the final model. LIMITATIONS: Results of this study may not generalize to community samples because subjects were drawn largely from a university-based outpatient psychiatric clinic. CONCLUSIONS: These findings stress the importance of social withdrawal, anhedonia, depressive cognitions, suicidal thoughts, and psychomotor retardation when trying to identify MDD among ADHD youths. PMID- 17276515 TI - Females of the communally breeding rodent, Octodon degus, transfer antibodies to their offspring during pregnancy and lactation. AB - Females in numerous rodent species engage in communal nesting and breeding, meaning that they share a nest to rear their young together. One potential benefit to communally nesting mothers is that infants improve their immunocompetence. Thus, suckling from two or more females might provide newborns with a more diverse array of antibodies and defensive cells. As a first step toward testing the immunocompetence hypothesis, we assessed whether female degus (Octodon degus), a communally nesting and breeding caviomorph rodent, transfer immunoglobulins to their young through the yolk sac or placenta while in the uterus and, during lactation, through milk. With this aim, adult degu females were immunized with four antigens, including two mollusk hemocyanins from Concholepas and Megathura (CCH and KLH, respectively), porcine thyroglobulin and tetanus toxoid. Specific antibodies against the experimental antigens were used to track the origin of antibodies in the young. To establish the presence of specific antibodies of IgG and IgA isotypes in sera and milk of animals, an indirect enzyme-linked immunosorbent assay (ELISA) was developed. Degu females produced specific antibodies against antigens not found in their natural environment, and mothers were able to transfer the induced antibodies to their litters during pregnancy (IgG) and during lactation (IgA). However, we recorded only limited evidence of degu offspring acquiring antibodies from lactating mothers other than their own, giving little support to the increased immunocompetence hypothesis. PMID- 17276514 TI - Therapeutic drug and cardiovascular disease risk monitoring in patients with bipolar disorder. AB - OBJECTIVES: We assessed whether patients with bipolar disorder received serum drug level and toxicity monitoring for mood stabilizers and assessment of cardiovascular disease (CVD)-related risk factors attributed to atypical antipsychotic medications. METHODS: A population-based study of individuals with bipolar disorder was conducted between July 2004 and July 2006. Based on American Psychiatric and American Diabetes Association guidelines, we assessed whether patients received recommended drug level and toxicity monitoring tests on or within 6 months for mood stabilizers, and lipid and glucose tests for atypical antipsychotics. Multivariable regression was used to determine the patient factors associated with receipt of lab tests. RESULTS: Of the 435 patients (mean age=49 years, 14.3% female, 22.8% nonwhite), 60.3% were currently prescribed mood stabilizers and 65.5% were prescribed atypical antipsychotics. Overall, 39.7% received a serum drug level for mood stabilizers, 38.8% received a thyroid function test for lithium, and the majority (71.4%-75.9%) received complete blood counts and hepatic function tests for valproate or carbamazepine. About half of patients prescribed atypical antipsychotics received cholesterol counts (49.6%), and 68.7% received serum glucose levels. After adjusting for patient factors, women prescribed atypical antipsychotics were less likely than men to receive cholesterol counts (OR=0.43; p<0.05). LIMITATIONS: Single-site retrospective study and a relatively short observation period. CONCLUSIONS: About half of patients received recommended lab tests for mood stabilizers and atypical antipsychotics. Additional research regarding whether the receipt of these lab tests is associated with improved outcomes will inform efforts to improve quality of care related to drug toxicities and CVD risk factors in patients with bipolar disorder. PMID- 17276516 TI - Internal consistency of Waldrop Physical Anomaly Scale in schizophrenic patients. AB - The aim of the study is to investigate the reliability (internal consistency) of the Waldrop Physical Anomaly Scale in patients with schizophrenia. The subjects were 76 schizophrenic patients (43 men, 33 women) and 82 normal controls (42 men, 40 women) of Bulgarian origin who were examined for minor physical anomalies. The correlations between the anomalies are low in schizophrenia, which indicates poor internal consistency of the scale, probably due to the heterogeneity of the anomalies in terms of location, character, and time of prenatal development. Some sex-related differences in the scale's reliability are indicated. The findings suggest the necessity of a more comprehensive scale by including informative morphogenetic variants, which can provide reliable anomaly assessment, distinguishing between minor malformations and phenogenetic variants and indicating the possible period of prenatal adversity. PMID- 17276517 TI - Tumour necrosis factor-alpha (TNF-alpha) increases nuclear factor kappaB (NFkappaB) activity in and interleukin-8 (IL-8) release from bovine mammary epithelial cells. AB - Epithelia play important immunological roles at a variety of mucosal sites. We examined NFkappaB activity in control and TNF-alpha treated bovine mammary epithelial monolayers (BME-UV cells). A region of the bovine IL-8 (bIL-8) promoter was sequenced and a putative kappaB consensus sequence was identified bioinformatically. We used this sequence to analyse nuclear extracts for IL-8 specific NFkappaB activity. As a surrogate marker of NFkappaB activation, we investigated IL-8 release in two models. Firstly in BME-UV monolayers, IL-8 release in the presence of pro- and anti-inflammatory agents was determined by enzyme-linked immunosorbent assay (ELISA). Secondly, we measured IL-8 secretion from a novel model of intact mucosal sheets of bovine teat sinus. IL-8 release into bathing solutions was assessed following treatment with pro- and anti inflammatory agents. TNF-alpha enhanced NFkappaB activity in bovine mammary epithelial monolayers. p65 NFkappaB homodimer was identified in both control and TNF-alpha treated cells. Novel sequencing of the bovine IL-8 promoter identified a putative kappaB consensus sequence, which specifically bound TNF-alpha inducible p50/p65 heterodimer. TNF-alpha induced primarily serosal IL-8 release in the cell culture model. Pre-treatment with anti-TNF or dexamethasone inhibited TNF-alpha induced IL-8 release. High dose interleukin-1beta (IL-1beta) induced IL 8 release, however significantly less potently than TNF-alpha. Bovine mammary mucosal tissue released high basal levels of IL-8 which were unaffected by TNF alpha or IL-1beta but inhibited by both dexamethasone and anti-TNF. These data support a role for TNF-alpha in activation of NFkappaB and release of IL-8 from bovine mammary epithelial cells. PMID- 17276519 TI - Treating leprosy: an Erb-al remedy? AB - The leprosy pathogen Mycobacterium leprae attacks Schwann cells in the peripheral nervous system, causing them to demyelinate. Recent work by Tapinos et al. shows that a direct mechanism of demyelination induced by M. leprae depends on the binding of the bacterium to the receptor tyrosine kinase ErbB2 on Schwann cells and the resulting activation of the Ras-Raf-MEK-ERK pathway. These findings have relevance for the potential treatment of leprosy and they highlight parallels between the dedifferentiation signal in leprosy and that in nerve injury and cancer. PMID- 17276518 TI - Carrier frequency of the 35delG and A1555G deafness mutations in the Argentinean population. Impact on the newborn hearing screening. AB - OBJECTIVE: Hearing loss is a complex multifactorial disorder caused by genetic and environmental factors. The 35delG mutation in the GJB2 gene is the most prevalent mutation in Caucasian patients with genetic sensorineural deafness. The A1555G mutation in the mitochondrial 12S rRNA is the main genetic alteration associated with aminoglycoside-induced deafness. The aim of this study was to evaluate the prevalence of both mutations in general population of Argentina. METHODS: A total of 712 samples of unrelated healthy blood donors and 330 newborn dried blood spots were studied by PCR-RFLP. RESULTS: The 35delG mutation was detected in 11/ 712 unrelated blood donors. The carrier frequency found in this sample (1/65) proved to be lower than that found in Southern European countries, mainly Spain and Italy, from where Argentina originally received its major immigration waves. When the populations of Southern Europe were considered altogether, this difference reached statistical significance. The A1555G mutation was not found in any of the 1042 samples tested. CONCLUSIONS: Taking into account the 35delG carrier frequency found in this study, it could be estimated that 130 160 children with congenital deafness due to mutations in the connexin genes would be born per year in Argentina. In contrast, the mitochondrial mutation A1555G appears to be infrequent in general Argentinean population. PMID- 17276520 TI - Balancing prostanoid activity in the human vascular system. AB - The imbalance theory proposes that arterial thrombosis is dependent on a ratio or balance between the cyclooxygenase (COX)-1-dependent generation of thromboxane in platelets and the COX-2-dependent generation of prostacyclin in the endothelium. Accordingly, by reducing endothelium-derived prostacyclin levels, selective COX-2 inhibitors would increase susceptibility to vasoconstriction, platelet activation and atherothrombosis. This imbalance theory has been frequently used to legitimize the potential for increased cardiovascular risk associated with the use of these agents. Surprisingly, the imbalance theory is based not on human vascular biology but on the analysis of urinary prostacyclin metabolites. In this review, I discuss the theory in the context of direct studies of human vascular biology, which indicate that the imbalance theory is based on incorrect assumptions and is not plausible. PMID- 17276521 TI - Brain reward systems and compulsive drug use. AB - Compulsive drug intake is a hallmark of addiction, yet a mechanistic understanding of this process has been elusive. Drug use is initiated primarily to obtain the excitatory actions of addictive drugs on brain reward systems. Paradoxically, excessive drug intake can decrease the activity of reward systems, reflected in elevated intracranial self-stimulation thresholds in rats, probably by engaging compensatory mechanisms to counter drug effects. Recent evidence suggests that compulsive drug intake might develop in response to such adaptive decreases in brain reward systems. Further, the actions of addictive drugs on reward systems are susceptible to classical conditioning processes, providing a potential mechanism by which drug-paired stimuli can induce powerful cravings and precipitate relapse in abstinent drug users. These findings provide a conceptual framework for improving our understanding of compulsive drug use, and might facilitate the development of novel therapeutics for substance abuse disorders. PMID- 17276522 TI - Simultaneous detection of potato viruses, PLRV, PVA, PVX and PVY from dormant potato tubers by TaqMan real-time RT-PCR. AB - The requirements of sprouting dormant potato tubers for biological or serological assays or RNA extraction for nucleic acid and PCR assays add to the cost of virus screening. Recently, cheaper, reliable and more rapid methods for the screening of potato tuber-seed pieces for viruses have been developed that do not require sprouted tubers for indexing, including TaqMan real-time RT-PCR. Although the assays are often designed for minimal time and reagent use, they still require a time-consuming and laborious RNA extraction step. This paper describes an assay where four common potato-infecting viruses, Potato leafroll virus, Potato virus A, Potato virus X and Potato virus Y, were detected simultaneously from total RNA and saps of dormant potato tubers in a quadruplex real-time RT-PCR. Factors critical for the detection of these viruses in saps of dormant potato tubers included: optimum dilution and inhibition of RNAses, and the optimization of the reverse transcription and PCR steps. Potato virus detection directly from tuber saps was comparable to that from purified total plant RNA, and this represents significant savings of time and expense. The TaqMan system developed in this study detected between 200 and 400 copies of potato virus RNA. PMID- 17276523 TI - Impairment of lipid storage by cadmium in the European eel (Anguilla anguilla). AB - Because European silver eels (Anguilla anguilla) fast during their reproductive migration to the Sargasso Sea, the successful completion of their unusual life cycle depends on quantity of lipids stored beforehand. These lipids are mainly accumulated during the growth phase stage of the animals, called yellow eel, as triglycerides in muscle. They are then catabolized to provide sufficient energy to enable migration, gonad maturation and spawning. In the laboratory, we investigated the possible impact of cadmium on the lipid storage efficiency of yellow eels in order to evaluate the possible contribution of this pollutant to the reported decline of European eel populations. Eels were exposed to dissolved cadmium at nominal concentrations of 0 and 5 microgL(-1) for 1 month. Cd toxicity was then examined by studying the activity and expression level of several enzymes involved in liver lipolysis and lipogenesis and by determining lipid content in muscle. Contaminated eels showed a lower body weight growth with a lower efficiency of lipid storage compared to controls. Using two complementary approaches, genetic and enzymatic, it was possible to conclude that this impairment is mainly explained by an increased utilisation of triglycerides since cadmium contamination did not trigger a reduced fatty acid synthesis. These observations suggest an increased fat consumption in presence of cadmium, which could compromise successful reproduction. PMID- 17276524 TI - Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells. AB - BACKGROUND: GLP-1 is secreted into the circulation after food intake. The main biological effects of GLP-1 include stimulation of glucose dependent insulin secretion and induction of satiety feelings. Recently, it was demonstrated in rats and humans that GLP-1 can stimulate renal excretion of sodium. Based on these data, the existence of a renal GLP-1 receptor (GLP-1R) was postulated. However, the exact localization of the GLP-1R and the mechanism of this GLP-1 action have not yet been investigated. METHODS: Primary porcine proximal tubular cells were isolated from porcine kidneys. Expression of GLP-1R was measured at the mRNA level by quantitative RT-PCR. Protein expression of GLP-1R was verified with immunocytochemistry, immunohistochemistry and Western blot analysis. Functional studies included transport assessments of sodium and glucose using three different GLP-1 concentrations (200 pM, 2 nM and 20 nM), 200 pM exendin-4 (GLP-1 analogue) and an inhibitor of the dipeptidylpeptidase IV (DPPIV) enzyme (P32/98 at 10 microM). Finally, the expression of NHE3, the predominant Na(+)/H(+) exchanger in proximal tubular cells, was also investigated. RESULTS: GLP-1R, NHE3 and DPPIV were expressed at the mRNA level in porcine proximal tubular kidney cells. GLP-1R expression was confirmed at the protein level. Staining of human and pig kidney cortex revealed that GLP-1R was predominantly expressed in proximal tubular cells. Functional assays demonstrated an inhibition of sodium re-absorption with GLP-1 after 3 h of incubation. Exendin-4 and GLP-1 in combination with P32/98 co-administration had no clear influence on glucose and sodium uptake and transport. CONCLUSION: GLP-1R is functionally expressed in porcine proximal tubular kidney cells. Addition of GLP-1 to these cells resulted in a reduced sodium re-absorption. GLP-1 had no effect on glucose re-absorption. We conclude that GLP-1 modulates sodium homeostasis in the kidney most likely through a direct action via its GLP-1R in proximal tubular cells. PMID- 17276525 TI - Pharmacological and biochemical characterization of bradykinin B2 receptors in the mouse colon: influence of the TNBS-induced colitis. AB - This study analyzed bradykinin (BK)-evoked contractile responses in the mouse colon under normal and inflammatory conditions. BK and the preferential B(2) receptor agonists Hyp(3)-BK, Lys-BK, Met-Lys-BK and Tyr(8)-BK produced a marked and concentration-related contraction of the normal mouse colon, whereas the selective B(1) receptor agonist des-Arg(9)-BK had no effect. BK-induced contraction was concentration-dependently antagonized (in a non-competitive manner) by both B(2) receptor antagonists Hoe 140 and FR173657, but not the B(1) receptor antagonist des-Arg(9)-[Leu(8)]-BK. Analysis of the possible mechanisms implicated in the contractile responses of BK in the mouse colon revealed the involvement of the neural release of acetylcholine, the activation of L- and N type voltage-gated calcium channels, and the release of neuropeptides, prostanoids and leukotrienes. The contraction induced by BK was markedly increased in preparations obtained from TNBS-treated mice. The up-regulation of B(2) receptors following the induction of colitis was confirmed with binding studies using [(3)H]-BK, which revealed a marked increase in B(2) receptor densities, without alterations of affinity. We provide convincing evidence on the relevance of B(2) receptors in the mouse colon under normal conditions, as well as under an inflammatory profile of colitis. Selective B(2) receptor antagonists might well represent rational therapeutic options for treating inflammatory bowel diseases. PMID- 17276526 TI - Increased cell survival, migration, invasion, and Akt expression in PTHrP overexpressing LoVo colon cancer cell lines. AB - Parathyroid hormone-related protein (PTHrP) has been localized in human colon cancer tissue and cell lines. We have previously shown that PTHrP increases colon cancer cell proliferation, extracellular matrix adhesion, and cell-surface integrin alpha6beta4 expression. Since cancer cell migration, invasion, and survival are crucial components of metastasis, and colon cancer has a high metastatic potential, in this study we used the human colon cancer cell line LoVo as a model system to study the effects of PTHrP on these parameters. PTHrP expression was modulated by stable transfection with a construct expressing PTHrP (-36 to +139). We report that PTHrP increases cell migration, invasion, and survival. PTHrP altered cell morphology, with PTHrP-overexpressing cells exhibiting increased spreading and several long protrusions. PTHrP also increased the steady-state mRNA levels of the integrin alpha6 and beta4 subunits, indicating a direct and/or indirect effect of PTHrP on the transcriptional and/or post-transcriptional regulation of integrin alpha6 and beta4 expression. Integrin alpha6beta4 activates the phosphoinositol 3-kinase (PI3-K)/Akt pathway, leading to glycogen synthase kinase-3 (GSK-3) deactivation. PTHrP overexpression also led to an increase in active Akt and inactive GSK-3 levels, indicating that the PTHrP mediated upregulation of integrin alpha6beta4 expression may activate the PI3-K pathway, resulting in increased cell survival, migration and invasion. PMID- 17276529 TI - Comparison between stenting and balloon in elderly patients undergoing primary angioplasty for ST-segment elevation myocardial infarction. AB - BACKGROUND: Coronary stenting has been shown to improve clinical outcome in comparison with balloon angioplasty in patients with ST-segment elevation myocardial infarction (STEMI). However, few data have been reported so far in the elderly. Thus, the aim of the current study was to evaluate the benefits from routine stenting in this high-risk subset of patients. METHODS: In the Zwolle-6 randomized trial a total of 1683 consecutive patients with STEMI was randomized to stenting or balloon angioplasty without any exclusion criteria. One year follow-up data were available from all patients. RESULTS: Among a total of 143 patients older than 75 years, 73 were randomized to stent and 67 to balloon angioplasty. No difference was observed in 1-year mortality (17.1% vs 11.9%, p=NS), reinfarction (9.2% vs 11.9%, p=NS), target vessel revascularization (15.8% vs 14.9%, p=NS) or major adverse cardiac events (28.9% vs 26.9%, p=NS) between the groups at 1-year follow-up. CONCLUSION: In conclusion, our study showed that as compared to balloon angioplasty, the clinical benefits of routine coronary stenting in the setting of acute myocardial infarction may not be necessarily applicable to elderly patients. PMID- 17276528 TI - The integration of signaling by multiprotein complexes containing Raf kinases. AB - In vivo, eukaryotic cells are subjected simultaneously to a broad array of signals ranging from mitogens and inflammatory inputs to environmental stresses and developmental cues. The combinatorial nature of cellular signaling necessitates that a cell integrate its signal transduction pathways so as to implement rapidly and efficiently an appropriate suite of responses. Emerging evidence indicates that, over the course of evolution, cells have developed multiprotein signaling complexes, or "signalosomes" that mediate the coordinate regulation of different signaling pathways. Such molecular signal integration contrasts with the classical notion of signaling complexes assembled by scaffold proteins-entities that function to segregate specific pathways from one another. This review will focus on two signal integrating multiprotein complexes that involve Raf family kinases: the MLK3-B-Raf-Raf-1 complex and the Raf-1-Mst-2 complex. PMID- 17276527 TI - Biological consequences of dosage dependent gene regulatory systems. AB - Chromatin and gene regulatory molecules tend to operate in multisubunit complexes in the process of controlling gene expression. Accumulating evidence suggests that varying the amount of any one member of such complexes will affect the function of the whole via the kinetics of assembly and other actions. In effect, they exhibit a "balance" among themselves in terms of the activity of the whole. When this fact is coupled with genetic and biological observations stretching back a century, a synthesis emerges that helps explain at least some aspects of a variety of phenomena including aneuploid syndromes, dosage compensation, quantitative trait genetics, regulatory gene evolution following polyploidization, the emergence of complexity in multicellular organisms, the genetic basis of evolutionary gradualism and potential implications for heterosis and co-evolving genes complexes involved with speciation. In this article we will summarize the evidence for this potential synthesis. PMID- 17276530 TI - The impact of budgets for gatekeeping physicians on patient satisfaction: evidence from fundholding. AB - Between 1991 and 1998 English general practices had the option of holding budgets for prescribing and elective secondary care. Fundholding was reintroduced in 2005. We examine the effect of fundholding on patients' satisfaction with their practice, using a cross section of 4441 patients from 60 practices in the last year of fundholding (1998). We employ instrumental variables to allow for the endogeneity of fundholding. Patients of fundholders were less satisfied with the opening hours of their practice, their GP's knowledge of their medical history, with their GP's ability to arrange tests and willingness to refer to a specialist, and were more likely to agree that their doctor was more concerned about keeping costs down. Fundholder practices performed better on a number of process measures of care, and fundholding patients were more satisfied with additional non-medical services provided by the practice. The probability that patients were overall at least very satisfied with their GP practice was 0.073 (95% CI, 0.009-0.138) smaller in fundholding practices. PMID- 17276531 TI - Multi-attribute utility function or statistical inference models: a comparison of health state valuation models using the HUI2 health state classification system. AB - A key issue in health state valuation modelling is the choice of functional form. The two most frequently used preference based instruments adopt different approaches; one based on multi-attribute utility theory (MAUT), the other on statistical analysis. There has been no comparison of these alternative approaches in the context of health economics. We report a comparison of these approaches for the health utilities index mark 2. The statistical inference model predicts more accurately than the one based on MAUT. We discuss possible explanations for the differences in performance, the importance of the findings, and implications for future research. PMID- 17276532 TI - The earnings of informal carers: wage differentials and opportunity costs. AB - A substantial proportion of working age individuals in Britain are looking after sick, disabled or elderly people, often combining their work and caring responsibilities. Previous research has shown that informal care is linked with substantial opportunity costs for the individual due to forgone wages as a result of non-labour market participation. In this paper we show that informal carers exhibit further disadvantages even when participating. Using the British Household Panel Study (BHPS) we decompose wage differentials and show that carers can expect lower returns for a given set of characteristics, with this wage penalty varying along the pay distribution and by gender. Furthermore, opportunity costs from forgone wages and wage penalties are estimated and found to be substantial. PMID- 17276533 TI - A population-based case-cohort study of the risk of myocardial infarction following radiation therapy for breast cancer. AB - OBJECTIVE: To describe the risk of acute myocardial infarction (AMI) after radiation therapy (RT) for breast cancer (BrCa) in an exposed population. METHODS: We identified and validated cases of AMI (vAMI), by electrocardiographic or enzyme criteria, among all 6680 women who received post-operative RT following lumpectomy or mastectomy, within 12 months following diagnosis of BrCa between 1982 and 1988 in Ontario, Canada. We identified women without vAMI whose death certification was ascribed to AMI (dAMI). We abstracted risk factors and treatment exposures for a random sample of women from the 6680, and for all with vAMI or dAMI. The hazards of vAMI and of dAMI were estimated using multivariate Cox proportional hazards models, corrected for study design. RESULTS: We validated 121 cases of vAMI and identified 92 cases of dAMI. The risk of vAMI associated with RT to the left breast HR=1.96 (1.09,3.54) among women at age >/= 60 at time of RT, adjusted for history of smoking and prior MI. The adjusted HR dAMI=1.90 (1.08,3.35) for exposure to anterior internal mammary node (IMC) RT. Among women who received anterior left breast boost RT, increasing area of the boost is associated with adjusted HR vAMI=1.02 (1.00,1.03)/cm(2), and adjusted HR dAMI=1.02 (1.01,1.03)/cm(2). CONCLUSION: The risks of vAMI and dAMI following RT for BrCa are related to anatomic sites of RT (left breast, area of anterior left breast boost field, and anterior IMC field). PMID- 17276534 TI - Prevalence and numbers of coliphages and Campylobacter jejuni bacteriophages in New Zealand foods. AB - Vegetable samples were tested for the presence of coliphages. None of the 55 samples contained these phages at concentrations greater than 10 g(-1) (the limit of detection). Spiking and recovery experiments indicated that the method was efficient at detecting coliphage T4 added to the food, and so it was concluded that phage titres were not being falsely underestimated. In addition 51 samples of chicken skin from retail portions were tested for the presence and numbers of coliphages and for presence only of Campylobacter jejuni phages. Coliphages were isolated from 46 samples (90.2% positive), at up to 2570 PFU 10 g sample(-1) but no C. jejuni phages were isolated. Several other methods were used to isolate C. jejuni phages from retail chicken but none was successful. However, when pooled whole chicken rinses from 39 flocks were tested for the presence of C. jejuni phages, 11 (28.2%) of the flocks were positive. It is possible that phages present on birds at the start of processing were either inactivated or simply diluted out during spin chilling. These data add to the body of information indicating that phages can readily be isolated from certain foods and indicate that consumers are exposed to them on a regular basis. PMID- 17276535 TI - Molecular stochastic simulations of chromatophore vesicles from Rhodobacter sphaeroides. AB - A kinetic model is presented for photosynthetic processes under varying illumination based on the recently introduced steady state model of the photosynthetic chromatophore vesicles of the purple bacterium Rhodobacter sphaeroides. A stochastic simulation system is built up from independent copies of the different transmembrane proteins, each encapsulating its own set of binding sites and internal states. The proteins are then connected through pools for each of the metabolites. A number of steady state and time-dependent scenarios are presented showing that even under steady state conditions the stochastic model exhibits a different behavior than a continuous description. We find that the electronic coupling between the light harvesting complexes increases the efficiency of the core complexes which eventually allows the bacteria to bridge short illumination outages at already lower light intensities. Some new experiments are proposed by which the DeltapH dependent characteristic of the bc(1) complex or the proton buffering capacity of the vesicle could be determined. PMID- 17276538 TI - Fighting back against male-killers. AB - Male-killing endosymbionts create a genetic black hole into which host nuclear genes vanish. In a recent paper, Hornett et al. transferred male-killing Wolbachia between different strains of the butterfly Hypolimnas bolina through hybridization and backcrossing. Their results provide unambiguous evidence of genetic variation for resistance to male-killers. A possible consequence of such variation is that male-killing might appear and disappear quickly on an evolutionary timescale. PMID- 17276537 TI - A phase II study of days 1 and 8 combination of docetaxel plus gemcitabine for the second-line treatment of patients with advanced non-small-cell lung cancer and good performance status. AB - OBJECTIVE: We conducted a phase II trial to evaluate the efficacy and toxicity of a combination consisting of second-line docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum based chemotherapy. PATIENTS AND METHODS: ELIGIBILITY CRITERIA: histologically confirmed advanced NSCLC with progressive disease to platinum-based chemotherapy, ECOG performance status (PS) 0 or 1, and adequate kidney, liver and bone marrow function. Treatment consisted of docetaxel 36 mg/m(2) i.v. over 60 min followed by gemcitabine 1000 mg/m(2) i.v. over 30 min on days 1 and 8 of each 3-week cycle for a planned six cycles or unacceptable toxicity. RESULTS: Of the 52 patients enrolled, 50 were evaluable for response and toxicity. The mean age was 59 years (range 42-79), 46 male and 4 female. Histology subtypes were: adenocarcinoma 26 patients, bronchioloalveolar 1 patient, large cell carcinoma 5 patients, and squamous cell carcinoma 18 patients. Thirty-eight patients had ECOG PS 1 and 12 patients had PS 0. The median number of cycles administered was four (range 2-6). The overall response rate was 28%. The median follow-up was 9 months (range 5-34 months). The median survival time (MST) was 8.2 months (95% CI, 4-12%), and the 1 year survival was 25%. The median progression-free survival was 4.4 months (95% CI, 2-6%). In the Cox regression model, survival was only significantly affected by the PS. The median survival in patients with PS 0 was 17.8 months (95% CI, 18.8-21.8%) compared with a median survival for patients with PS 1 of 6.1 months (95% CI, 4.1-8.2%) (P=0.0057). TOXICITY: three patients had grade 3 anemia, three patients had grade 3 thrombocytopenia, four patients had grade 3 neutropenia and only one patient developed grade 4 febrile neutropenia. Non-hematologic toxicity was also mild; the most frequent was asthenia, with grade 3 in eight patients (16%), and one patient with grade 4. CONCLUSION: This regimen of docetaxel in combination with gemcitabine in advanced second-line NSCLC is an active and safe regimen. PMID- 17276536 TI - Reducible poly(amido ethylenediamine) for hypoxia-inducible VEGF delivery. AB - Delivery of the hypoxia-inducible vascular endothelial growth factor (RTP-VEGF) plasmid using a novel reducible disulfide poly(amido ethylenediamine) (SS-PAED) polymer carrier was studied in vitro and in vivo. In vitro transfection of primary rat cardiomyoblasts (H9C2) showed SS-PAED at a weighted ratio of 12:1 (polymer/DNA) mediates 16 fold higher expression of luciferase compared to an optimized bPEI control. FACS analysis revealed up to 57+/-2% GFP positive H9C2s. The efficiency of plasmid delivery to H9C2 using SS-PAED was found to depend upon glutathione (GSH) levels inside the cell. SS-PAED mediated delivery of RTP-VEGF plasmid produced significantly higher levels of VEGF expression (up to 76 fold) under hypoxic conditions compared to normoxic conditions in both H9C2 and rat aortic smooth muscle cells (A7R5). Using SS-PAED, delivery of RTP-VEGF was investigated in a rabbit myocardial infarct model using 100 mug RTP-VEGF. Results showed up to 4 fold increase in VEGF protein expression in the region of the infarct compared to injections of SS-PAED/RTP-Luc. In conclusion, SS-PAED mediated therapeutic delivery improves the efficacy of ischemia-inducible VEGF gene therapy both in vitro and in vivo and therefore, has potential for the promotion of neo-vascular formation and improvement of tissue function in ischemic myocardium. PMID- 17276539 TI - Sly FOXP2: genomic conflict in the evolution of language. PMID- 17276540 TI - Guidelines of care for acne vulgaris management. AB - DISCLAIMER: Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient. PMID- 17276541 TI - Liposomal amphotericin B in comparison to sodium stibogluconate for cutaneous infection due to Leishmania braziliensis. AB - BACKGROUND: New World cutaneous leishmaniasis among Israeli travelers is mostly acquired in the Amazon Basin of Bolivia where Leishmania viannia (V.) braziliensis is endemic. Treatment with systemic pentavalent antimonial compounds is effective in achieving clinical cure in only 75% of cases. In this study, we assessed liposomal amphotericin B (AmBisome) as an alternative treatment for cutaneous L (V.) braziliensis infection. METHODS: A prospective evaluation was performed for cutaneous leishmaniasis due to L (V.) braziliensis, proven by polymerase chain reaction. A 3-mg/kg AmBisome dose was given for 5 consecutive days, and a sixth dose on day 10, all in an outpatient setting. This therapy was compared with a series of historical patients who were treated with sodium stibogluconate (SSG). RESULTS: Seven consecutive patients, 5 males and 2 females, received AmBisome treatment. All were returned travelers infected in Bolivia; their mean age was 23.1 years; 5 had failed to respond to a full course of SSG; two had a primary lesion; none had mucosal lesions. All achieved complete clinical cure within less than 1 month. Mean follow-up of 12 months revealed no relapses. Side effects were mild, and none had to terminate treatment prematurely. Comparison of AmBisome to SSG treatment shows that the former is safer, with fewer recurrence rates. Additionally, the expense of the total care with AmBisome is less than with SSG: 45% less if SSG was given in an inpatient setting; 15% less when SSG was given in an outpatient setting. LIMITATIONS: This was a nonrandomized study, with relatively few patients. CONCLUSION: AmBisome treatment for L (V.) braziliensis appears to be effective, better tolerated, and to have more cost benefit in countries where hospital-care costs are significant. PMID- 17276542 TI - From sporadic atypical nevi to familial melanoma: risk analysis for melanoma in sporadic atypical nevus patients. AB - BACKGROUND: Atypical nevi (AN), present in either a familial or a sporadic setting, are strong indicators of increased melanoma risk. OBJECTIVE: To estimate the extent of this risk and the extent of reclassification of sporadic to familial cases during follow-up. METHODS: We studied 167 sporadic patients with AN (>or=5). At the end of follow-up we updated the family history regarding melanoma and performed germline mutation analysis of the known melanoma susceptibility genes. RESULTS: We found a relative risk for melanoma of 46.1 (95% confidence interval 21.0-87.5). Six of 167 patients were carriers of a CDKN2A mutation. At the end of follow-up, 10 of 136 patients with sporadic AN reported being a member of a melanoma family. LIMITATIONS: This study was conducted in an area with a founder mutation in many of its melanoma families; therefore the results may not be applicable to other populations. CONCLUSION: We report a high relative risk of 46.1 of melanoma development in patients with sporadic AN. A significant proportion of this Dutch cohort reported additional cases in their families over time. PMID- 17276543 TI - Measuring the stringency of states' indoor tanning regulations: instrument development and outcomes. AB - OBJECTIVES: We sought to describe the development of an instrument to quantify the stringency of state indoor tanning legislation in the United States, and the instrument's psychometric properties. The instrument was then used to rate the stringency of state laws. METHODS: A 35-item instrument was developed. An overall stringency measure and 9 stringency subscales were developed, including one measuring minors' access to indoor tanning. Stringency measures showed good internal consistency and interrater reliability. RESULTS: In all, 55% of the 50 states and the District of Columbia had any indoor tanning law, and 41% had any law addressing minors' access. Oregon, Illinois, South Carolina, Florida, Indiana, Iowa, and Rhode Island had high overall stringency scores, and Texas and New Hampshire were the most restrictive with regard to minors' access. LIMITATIONS: Measurement of actual enforcement of the laws was not included in this study. CONCLUSIONS: The instrument appears to be an easy-to-use, reliable, and valid methodology. Application of the instrument to actual laws showed that, in general, state laws are relatively weak, although there was considerable variability by state. PMID- 17276544 TI - Treatment of extensive cutaneous metastatic melanoma with topical diphencyprone. AB - Diphencyprone is a potent contact sensitizer sometimes used to treat alopecia areata and cutaneous warts. A patient with previous primary nodular melanoma on the scalp developed extensive, confluent cutaneous metastases near the primary site, unsuitable for treatment with surgery or radiotherapy. Topical treatment with diphencyprone as a single agent resulted in regression of all lesions, and the patient remains well 18 months later. Topical immunotherapy with diphencyprone was an inexpensive and well-tolerated treatment for extensive cutaneous melanoma metastases in our patient unsuitable for other therapies. PMID- 17276546 TI - Measurement of compliance with hand hygiene. AB - Compliance with hand hygiene is widely recognized as the most important factor in preventing transmission of infection to patients in health care settings. However, there is no standardized method for measuring compliance. The three major methods used are direct observation, self-report and indirect measurement of hand hygiene product usage. This review discusses the methods of compliance monitoring and the advantages and drawbacks of each. PMID- 17276547 TI - Intimate partner violence and emergency department screening: computerized screening versus usual care. AB - STUDY OBJECTIVE: To compare a computer-based method of screening for intimate partner violence (intimate partner violence) with usual care in an emergency department (ED) setting. METHODS: During 3 distinct but consecutive 2-week periods, women who presented to the ED were asked to complete a computer-based health survey with or without intimate partner violence screening questions in addition to receiving usual intimate partner violence care (ie, screened voluntarily by ED providers and documented in medical record). The screening, detection, referral and service rates were compared between women who completed the computer-based health survey with the intimate partner violence screening questions to usual care. RESULTS: Of the 411 women who completed the computer based health survey with the intimate partner violence questions, 99.8% were screened for intimate partner violence compared to 33% of the 594 women who received usual care (67.1% difference; 95% CI 63.3%, 70.9%). The computer-based health survey detected 19% intimate partner violence positive whereas usual care detected 1% (17.8% difference; 95% CI 13.9%, 21.7%). Referral to social work was higher among those screened by the computer-based health survey (10%) versus usual care (<1%) (9.7% difference; 95% CI 6.7%, 12.7%). Only 20 subjects received intimate partner violence services, although it was slightly higher among those screened by the computer-based health survey (4%) compared to usual care (1%) (4.0% difference; 95% CI 2.0%, 6.1%). CONCLUSION: We found that a computer-based approach led to significantly higher intimate partner violence screening and detection rates compared to usual care. Receipt of intimate partner violence services was also higher than usual care but was not optimal. Computer technology makes routine screening easier and allows us to redirect our energies to addressing patients' intimate partner violence problems. PMID- 17276549 TI - Accessibility of Internet references in Annals of Emergency Medicine: is it time to require archiving? AB - STUDY OBJECTIVE: We seek to evaluate the accessibility of all Internet references appearing in Annals of Emergency Medicine from 2000, 2003, and 2005. Secondary objectives are to determine whether the number of Internet references is increasing and to describe how Internet references are inaccessible. METHODS: We visually scanned all articles for references made in the printed version of Annals of Emergency Medicine for 2000, 2003, and 2005. We identified the Internet references and grouped them into 11 categories according to the results of entering the uniform resource locator (URL) into the Internet browser. RESULTS: We identified 15,745 references published in Annals of Emergency Medicine. The proportion of Internet references increased from 1% of the total references in 2000 to 5.4% in 2005. Internet references were not readily accessible for 40 of 51 Internet references in 2000 (78%; 95% confidence interval [CI] 65% to 88%), 161 of 286 Internet references in 2003 (56%; 95% CI 50% to 62%), and 111 of 249 Internet references in 2005 (45%; 95% CI 39% to 51%). Inaccessibility was most commonly manifested by URLs that no longer link to active Web sites (172 of 312 inaccessible Internet references [55%]; 95% CI 50% to 61%) and URLs that linked to generic home pages where the authors' referenced material could not be found (115 of 312 inaccessible Internet references [37%]; 95% CI 32% to 42%). CONCLUSION: In Annals of Emergency Medicine, older Internet references appear to be less accessible than newer references. Internet reference archiving is one solution to preserving this information for future readers. PMID- 17276548 TI - Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial. AB - STUDY OBJECTIVE: We compare the analgesic efficacy and adverse effects of oral prednisolone/acetaminophen and oral indomethacin/acetaminophen combination therapy in the treatment of acute goutlike arthritis in patients presenting to an emergency department (ED). METHODS: This is a double-blind, randomized, controlled study in a university hospital emergency department (ED) in the New Territories of Hong Kong. Patients older than 17 years and presenting between February 1, 2003, and June 30, 2004, with a clinical diagnosis of goutlike arthritis were randomized to receive either oral prednisolone/acetaminophen or oral indomethacin/acetaminophen combination therapy. Primary outcome measures were pain scores, time to resolution of symptoms and signs, and adverse effects. Secondary outcome measures were the need for additional acetaminophen and relapse rate. RESULTS: There were 90 patients randomized: 46 patients to the indomethacin group and 44 patients to the prednisolone group. Baseline characteristics, including pain scores, were similar in the 2 groups. Both treatment groups had a similar decrease in pain score in the ED. The mean rate of decrease in pain score with activity for indomethacin was -1.7+/-1.6 (SD) mm per day and for prednisolone was -2.9+/-2.0 (SD) mm per day (mean difference 1.2 mm/day; 95% confidence interval 0.4 to 2.0 mm/day; P=.0026). Although these differences were statistically significant, at no time was the difference in mean pain score greater than 13 mm. Therefore, it is unclear whether these differences are clinically significant. The mean total dose of acetaminophen consumed by the prednisolone group was significantly more than in the indomethacin group (mean 10.3 g, range 1 to 21 g versus mean 6.4 g, range 1 to 21 g). Twenty-nine patients in the indomethacin group and 12 patients in the prednisolone group experienced adverse effects (P<.05). The commonest adverse effects in the indomethacin group were nausea, indigestion, epigastric pain, dizziness, and gastrointestinal bleeding (N=5; 11%). None of the patients in the prednisolone group developed gastrointestinal bleeding. The relapse rate for both groups was similar. CONCLUSION: In the treatment of acute goutlike arthritis, oral prednisolone/acetaminophen combination is as effective as oral indomethacin/acetaminophen combination in relieving pain but is associated with fewer adverse effects. PMID- 17276550 TI - In vitro and in vivo characterization of opioid activities of endomorphins analogs with novel constrained C-terminus: evidence for the important role of proper spatial disposition of the third aromatic ring. AB - In the present study, the C-terminus of endomorphin (Tyr(1)-Pro(2)-Trp/Phe(3) Phe(4)-NH(2), EMs) analogs [Xaa(4)-R]EMs, modified by substitution of a non aromatic residue for Phe(4) and ending up with -NH-benzyl, were designed to generate an atypical conformationally constrained peptide set. We investigated the effects of these analogs on the opioid receptors affinity, guinea pig ileum (GPI) and mouse vas deferens (MVD) activity, system arterial pressure (SAP), heart rate (HR), antinociception and colonic motility. Analogs 5 ([D-V(4) Bzl]EM1) and 10 ([D-V(4)-Bzl]EM2), which exhibit appropriate spatial orientations of the third aromatic ring, were about 3-4 times more potent than their parents both in vivo and in vitro. However, a drastic loss of activity was found in analogs 2 ([A(4)-Bzl]EM1) and 7 ([A(4)-Bzl]EM2), which possess improper spatial orientations of the third aromatic ring. Interestingly, analog 7 or 3 ([G(4) Bzl]EM1), when injected intravenously (i.v.), produced significantly different changes in SAP from their parents. Surprisingly, analog 4 displayed relatively higher vasodepressor activity but significantly less potent colonic contractile activity than analog 5. This may be elicited by the differences in the spatial disposition of the third aromatic ring, which were verified by molecular modeling. Our results indicate that the proper spatial disposition of the third aromatic ring plays an important role in the regulation of pharmacological activities of EMs. PMID- 17276551 TI - Melatonin and the aging brain. AB - The events associated with brain aging are enumerated with emphasis on increased oxidative and inflammatory processes and on mitochondrial dysfunction. Several of these factors are further increased in a wide range of overt age-related neurological diseases. This generality has given impetus to concepts concerning similar therapeutic approaches common to a series of neurodegenerative disorders. Animal and cell culture models of several such disorders have benefited from the application of melatonin. The mechanisms underlying the neuroprotective properties of melatonin are likely to involve activation of specific melatonin receptors. This can lead to modulation of transcription factors and consequent altered gene expression, resulting in enhancement of antioxidant enzymes and downregulation of basal levels of inflammation. Melatonin has potential utility both in slowing normal brain aging and in treatment of neurodegenerative conditions. This is reinforced by the low cost of melatonin and its very low toxic hazard. PMID- 17276552 TI - Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11-15 years: a randomised controlled trial. AB - This trial assessed the immunogenicity, safety and reactogenicity of a two-dose hepatitis B immunisation regimen (thiomersal-free Engerix-B 20 microg HBsAg doses 6 months apart) compared to the standard three-dose vaccination regimen (preservative-free Engerix-B 10 microg HBsAg doses, 0, 1, 6 month dose schedule) in healthy adolescents aged 11-15 years. Subjects were randomly assigned (2:1 ratio) to one of the two regimens (258 to the two-dose [20 microg] and 126 to the three-dose [10 microg] regimen) (Study ID 103860/280). One month after the final vaccine dose, the seroprotection (anti-HBs >or=10mIU/ml) rate in the two-dose (20 microg) group (233/241 individuals -96.7% seroprotected) was non-inferior to the seroprotection rate in the three-dose (10 microg) group (111/113 individuals 98.2% seroprotected). Both regimens were shown to be safe and well tolerated. Two doses of Engerix-B (20 microg HBsAg) could be considered as an alternative to standard three-dose Engerix-B (10 microg HBsAg) immunisation for adolescents aged 11-15 years. PMID- 17276553 TI - Identifying the epitope-specific T cell response to virus infections. AB - Virus infection induces an adaptive immune response by T cells that is specific for defined viral epitopes. The epitope-specific analysis of T cells has become an important tool for investigating the anti viral response following infection or vaccination. In this review, the inherent differences in the procedures to identify the epitopes are discussed. Specifically, the screening of lymphocytes for epitope specific responses and the usage of mass spectrometry for sequencing of viral epitopes are evaluated. PMID- 17276554 TI - Changing perspective on immunization against influenza. AB - Current vaccination strategies against influenza rely on decades old technology of strain selection and prolonged labor-intensive, embryonated chicken-egg based production methods. Although, containing both major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), the immunity engendered by these vaccines is dominated by the anti-HA response. Consequently, current vaccines are susceptible to failure resulting from significant antigenic drift or shift in the time elapsing from the selection of the vaccine candidate strain and wild-type virus exposure. Therefore, immunity may be of short duration. There must be a change in vaccine strategy to include immunization with both HA and NA to broaden the immune response against influenza. Inclusion of the more slowly evolving NA in a vaccine against influenza will reduce the vulnerability to antigenic changes in a potential emerging influenza virus. Alternative production technologies such as recombinant baculovirus and yeast should be explored to decrease vaccine production times. PMID- 17276555 TI - Dermal testing of vaccines for children at high risk of allergies. AB - Vaccinations for children with allergic diseases often need to be postponed or terminated because of the presumed risk of an immediate-type allergic reaction such as anaphylaxis. A new skin test protocol for predicting allergic reactions using the vaccine itself and the following stepwise vaccination method were developed and tested. Intradermal tests using 1:10 and 1:100 diluted measles vaccine indicated that the former was superior to the latter because a positive reaction against 1:10 diluted vaccine was found in 28.6% of 49 patients with severe allergic diseases including bronchial asthma, atopic dermatitis, food allergies and allergies to two or more allergens with high levels of IgE, as compared with the reaction against 1:100 diluted vaccine in 10.2% of the patients. Patients negative for 1:10 skin tests were safe from the following full dose vaccine shots. Three patients showed very strong local reactions against measles vaccine, and avoided receiving the following full-dose shot. Positive reactions to skin tests of 1:10 diluted vaccine were found in 11 patients, who were given stepwise vaccinations. Three patients had adverse reactions, and two of them had been negative for 1:100 skin tests. In the case of influenza vaccine, skin tests were again more sensitive to 1:10 than to 1:100 diluted vaccine, because 3 out of 14 patients with positive reactions showed immediate-type adverse reactions against the following stepwise vaccinations, and 1 of them was negative for the 1:100 skin test. Moreover, the results of the skin prick test (undiluted vaccine) and the intradermal skin test (1:10 diluted vaccine) indicated that the latter was more useful in both cases of measles (54 patients) and influenza vaccine (69 patients). Overall, the skin test using 1:10 diluted vaccine was the more suitable for predicting an immediate-type reaction to measles and influenza vaccinations. Patients having negative 1:10 skin tests can be expected to show no adverse reactions to the remaining injections and even the positive subjects will complete the course of vaccine doses by the stepwise method. PMID- 17276556 TI - Mimotope vaccines for cancer immunotherapy. AB - Cancer vaccines need to be designed to effectively induce tumor-specific CD8(+) T cells, the key effector cells in immune responses against tumors. These T cells recognize peptides generated from cellular proteins by limited proteolysis, and bound and presented at cell surfaces by MHC class I molecules. Mimotopes, mimetics of T cell epitopes, have been derived from known epitopes by sequence modification, or developed de novo using combinatorial peptide libraries to scan the entire sequence space for peptides that induce the desired T cell responses. Mimotopes of both types have been tested in clinical vaccination trials for treatment of cancer. PMID- 17276558 TI - Protection and immune response in pigs intradermally vaccinated against porcine reproductive and respiratory syndrome (PRRS) and subsequently exposed to a heterologous European (Italian cluster) field strain. AB - The purpose of this study was to assess the immune response in pigs intradermally vaccinated with a commercially available attenuated porcine reproductive and respiratory virus (PRRSV) vaccine (Porcilis PRRS) and subsequently exposed to a heterologous (Italian cluster) field strain of virulent PRRSV. A total of 18, 4 week-old pigs seronegative for PRRSV were allocated to 1 of 3 groups (groups A, B, and C). At 5 weeks of age, pigs of groups A (n=6 pigs) and B (n=6 pigs) were vaccinated intramuscularly and intradermally, respectively, with Porcilis PRRS. The more conventional intramuscular route of vaccination was included for comparative purposes with the intradermal route of vaccination (performed with the I.D.A.L. vaccinator). Pigs of group C (n=6 pigs) were kept as nonvaccinated controls. At post-vaccination (PV) days 7, 14, 21, 28, and 35, blood samples were collected for detection of vaccine virus (PCR) and antibodies (ELISA), and for changes in PBMC (flow cytometry). At PV day 35, pigs of all groups were each exposed (challenged) intranasally to a heterologous field strain (78% ORF5 sequence homology between vaccine and field virus) belonging to the Italian cluster of the European genotype of PRRSV. At post-challenge (PC) days 0, 3, 7, 10, 13, and 17, blood samples were collected for detection and quantitation of virus and antibodies, and for changes in PBMC as described above for blood samples collected PV. Throughout the experiment all pigs were observed daily for clinical signs. At PC days 7 and 17, two pigs and four pigs, respectively, of each group were euthanized and examined for macroscopic lesions. Following vaccination some pigs of groups A and B had a detectable viremia that in two pigs (one pig of group A and one pig of group B) lasted until PV day 28. However, all pigs (groups A, B, and C) remained clinically normal. All vaccinated pigs developed a serological response (ELISA) to PRRSV. Presumptive evidence for vaccine-induced protective immunity against the heterologous challenge strain was provided by finding that viremia following challenge was generally less (incidence) and significantly less (titers) in vaccinated pigs than in nonvaccinated pigs. No differences were apparent between pigs vaccinated intramuscularly and those vaccinated intradermally. The absence of virulent-virus induced clinical signs and macroscopic lesions in nonvaccinated as well as in vaccinated pigs precluded a more definitive evaluation of the magnitude of protective immunity provided by vaccination or by the route of vaccination. Some likely treatment-associated changes in lymphocyte subpopulations were observed among the three treatment groups. These changes and their potential relationship to protective immunity are discussed. PMID- 17276559 TI - Receptor mediated targeting of M-cells. AB - The intestinal epithelium is a complex system of highly specialised cells that provide digestive and absorptive functions as well as innate and adaptive immunity. Induction of an adaptive immune response in the intestine can occur through the interaction of antigen with M-cells that overlay the lymphoid aggregates of the intestine (Peyer's patches). This study demonstrated that specific common microbial pathogen-associated molecular patterns are recognised by pattern recognition receptors on the surface of the M-cells and this interaction initiates transcytosis through the M-cell of particulate antigen from the intestinal milieu to underlying antigen presenting cells within the Peyer's patch. The study has found that among the pattern recognition molecules that have a role in recognising bacterial components, the apical expression of alpha5beta1 integrin was important for the transcytotic function of M-cells. A proportion of intestinal enterocytes transform to an M-cell morphology in vitro, when cultured with Peyer's patch cells and our studies have demonstrated that CD4+ cells are integral for the development of M-cells in vitro. PMID- 17276557 TI - Non-toxic Pseudomonas aeruginosa exotoxin A expressing the FMDV VP1 G-H loop for mucosal vaccination of swine against foot and mouth disease virus. AB - Synthetic peptides derived from the G-H loop of the foot and mouth disease virus (FMDV) capsid protein VP1 are relatively poor at recapitulating the native conformation present in the virus, and thus are often poor immunogens. We hypothesized that a candidate mucosal vaccine against FMDV could be developed using the non-toxic Pseudomonas aeruginosa exotoxin A (ntPE) to deliver the G-H loop in its native conformation. An added benefit of this approach is the potential for ntPE to serve as an effective carrier/adjuvant molecule for delivery of the fusion protein across the epithelial barrier by virtue of its capacity to bind to CD91. A chimeric protein (ntPE-GH) was generated by inserting the coding sequence of the G-H loop into an expression plasmid encoding ntPE, in place of the native Ib loop. Recombinant ntPE-GH and wild-type ntPE were each expressed in Escherichia coli, purified over a nickel resin, then administered intranasally to the pigs, with or without the mucosal adjuvant cholera toxin (CT). Both the ntPE and ntPE-GH induced mucosal and systemic immune responses against ntPE; moreover, ntPE-GH administered without CT induced anti-GH loop serum IgG antibodies. In conclusion, these data demonstrate that ntPE can be used as a mucosal carrier/adjuvant to induce an immune response against the VP1 G-H loop of FMDV. PMID- 17276560 TI - Intra-cultivar variability of the soil-to-grain transfer of fallout 137Cs and 90Sr for winter wheat. AB - Differences between the root uptake of fallout radionuclides by different cultivars ('inter-cultivar' variability) growing on the same field may be influenced not only by genetic differences of the cultivars, but also by the spatial variability of the soil-to-grain transfer within the cultivation area of each cultivar. This 'intra-cultivar' variability was investigated in 2001 and 2002 for 137Cs and 90Sr using three winter wheat cultivars with four replicates for each cultivar at three different sites in Bavaria, Germany. The intra cultivar variability proved to be in the same range as the inter-cultivar variability which was determined earlier at the same sites for both radionuclides. An ANOVA of the 137Cs data set revealed that the variability of the 137Cs soil-to-grain transfer was caused by the soil and climate (year) at the field sites and the interaction of cultivar and field. A significant contribution of the factor 'cultivar' alone to the variability could not be detected. This may be due to the complex environmental conditions to which plants are exposed in field experiments. To find wheat cultivars with minimal uptake of fallout radionuclides it may be better to examine the molecular mechanisms of their root uptake in order to identify targets for breeding "safer" plants. PMID- 17276561 TI - Case series of 148 tongue-tied newborn babies evaluated with the assessment tool for lingual frenulum function. AB - OBJECTIVE: the Assessment Tool for Lingual Frenulum Function (ATLFF) is the only available tool designed to assess newborn babies for the severity of tongue-tie. The aim of this study was to describe the ATLFF scores obtained on a series of 148 tongue-tied newborn babies. DESIGN: prospective case series. SETTING: a 420 bed community hospital in St. Paul, Minnesota, USA. PARTICIPANTS: newborn babies admitted to the normal newborn nursery from October 1, 2000 to May 1 2002. MEASUREMENTS AND FINDINGS: all babies in the nursery were examined for tongue tie. One-hundred and forty-eight tongue-tied babies were examined using the ATLFF by at least one of three examiners. The ATLFF could not be completed on five babies. Of the remaining babies, 40 (28%) received 'perfect' scores, five (3.5%) received 'acceptable' scores, and 19 (13.3%) received 'function impaired' scores. The remaining 79 (55.2%) babies received scores that did not fall into any of the three categories of scores. The inter-rater agreement on whether or not the baby had a score of 'function impaired' on the ATLFF was moderate (kappa=0.44). KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: few tongue-tied babies had a score of 'function impaired' on the ATLFF. It is a major limitation of the ATLFF that it does not classify most babies. The development and testing of a useful tool to determine which tongue-tied babies will have difficulty with breast feeding remains a research priority. PMID- 17276562 TI - Congenital unilateral upper limb muscular hypertrophy associated with contracture of an extrinsic extensor tendon. AB - We report a case of congenital unilateral upper limb muscular hypertrophy which presented with loss of extensor tendon excursion of a single digit in late adolescence. The reason for the problem arising is not clear and is not clearly explained by the underlying congenital pathology. PMID- 17276563 TI - Re: Comparison between percutaneous transverse fixation and intramedullary K wires in treating closed fractures of the metacarpal neck of the little finger. PMID- 17276564 TI - Arthroscopic interposition arthroplasty of the first carpometacarpal joint. AB - First carpometacarpal joint arthritis is a common condition encountered by hand surgeons. Traditionally, surgical approaches have included arthrodesis, trapeziectomy or reconstructive arthroplasty techniques. Previously, we described a technique for arthroscopic debridement and interposition arthroplasty of the first carpometacarpal joint. Patients with Eaton stages II and III symptomatic first carpometacarpal joint arthritis recalcitrant to >6 months of non-operative therapy underwent arthroscopic debridement of the first carpometacarpal joint with interposition of an acellular dermal matrix allograft (GRAFTJACKET). In this paper, we describe outcomes following this procedure. Postoperatively, all patients reported symptomatic relief and 94% stated that they were partially, or completely, satisfied. More than 70% of patients reported no to mild difficulty in performing activities of daily living (average grip strength = 18.5 kg, pinch strength = 3.9kg). Complications were minimal. Outcomes from this study compare favourably to those of other series, demonstrating that this technique is a viable option for treatment of Eaton stages II and III first carpometacarpal arthritis. PMID- 17276566 TI - Impacts of landscape remediation on the heavy metal pollution dynamics of a lake surrounded by non-ferrous smelter waste. AB - Heavy metal concentrations and potential bioavailability are reported for sediment in a shallow flood detention lake surrounded by reclaimed, smelter contaminated land. A range of sediment column proxy indicators is used to explore changes in pollution dynamics with remediation. Sediment concentrations of Pb and Zn are high at approximately 600 and 20,000 mg kg(-1), respectively. Less than 7% of total Pb is potentially bioavailable following sequential extraction as opposed to 47% of Zn. Metal transfer mechanisms to lake sediment include detrital inputs, scavenging by particulates and biogeochemical precipitation. Sedimentary evidence indicates that detrital inputs to the lake declined following land reclamation after which it is proposed that dissolved inputs increased with leaching of reworked waste material. Whilst downcore metal profiles may be subject to post-depositional change, diatom analysis suggests more recent improvements in water quality. The potential for post-remediation pollution episodes relating to metal release from historic sedimentary stores should be considered in future remediation strategies. PMID- 17276567 TI - We also need bold experiments: a response to Starfield's "Commentary: Pathways of influence on equity in health". PMID- 17276568 TI - The political economy of AIDS leadership in developing countries: an exploratory analysis. AB - The commitment of high-level government leaders is widely recognized as a key factor in curbing national AIDS epidemics. But where does such leadership come from? This paper presents a quantitative analysis of the determinants of AIDS leadership in 54 developing countries, using the 2003 AIDS Program Effort Index "political support" score as an indicator of political commitment. Explanatory variables include measures of political institutions as well as economic development and integration. Models developed in the analysis explain over half of the variation in commitment across the countries in the sample. In particular, press freedoms, income equality, and HIV prevalence stand out as determinants of political commitment. PMID- 17276569 TI - Involvement of nitric oxide in cocaine-induced erections and ejaculations after paradoxical sleep deprivation. AB - OBJECTIVES: As nitric oxide (NO) is involved in penile erectile (PE) function and also influences the sleep-wake cycle, we speculated that NO could play a role in PE and ejaculation of paradonical sleep deprivation (PSD) rats. METHODS: Animals were pretreated with N(G)-nitro-L-arginine methyl ester (L-NAME, ip) and L arginine (ip and icv) prior to saline or cocaine injection. RESULTS: Cocaine induced PE in 90% of PSD rats, 60% of which ejaculated. L-NAME reduced the frequency of erection, but had no effect in the proportion of PSD-cocaine injected rats displaying this response. L-NAME had no effect in saline groups. L Arginine in PSD-saline rats reduced the proportion of animals displaying PE at the highest dose and reduced the frequency of PE at all doses in both saline and cocaine groups. The icv administration of L-arginine reduced PE only in PSD cocaine rats. Results indicate that common to both drugs, whether it was NO synthase (NOS) inhibitor or NO precursor, was their capacity to strongly reduce PE frequency in cocaine-treated rats. Moreover, L-arginine (ip) played a relevant inhibitory role in the erection displayed by PSD rats. CONCLUSIONS: Our findings suggest that the stimulating effects of PSD associated or not with cocaine on erection can be modified by alterations in the NO system. PMID- 17276570 TI - Anti-inflammatory and lysosomal stability actions of Cleome gynandra L. studied in adjuvant induced arthritic rats. AB - The present study was aimed to assess the anti-arthritic nature of Cleome gynandra L. (Cat's whiskers) against Freund's complete adjuvant induced arthritis in rats. The ethanolic extract of C. gynandra was administered orally at a dose of 150 mg/kg body weight for 30 days to the experimental rats after the induction of adjuvant arthritis. The anti-inflammatory activity of C. gynandra leaves was assessed by paw volume measurement, and its capacity to stabilize lysosomal enzyme activities in the plasma and liver of control and experimental rats. The activity of pathophysiological enzymes such as AST, ALT, ALP, cathepsin-D, beta glucuronidase, N-acetyl-beta-glucosaminidase LDH and the levels of glycoproteins were also estimated in plasma and liver. The increased levels of both lysosomal enzymes and protein-bound carbohydrates in arthritic rats were significantly suppressed to near normal level by the administration of C. gynandra extract. Further, the significantly elevated plasma levels of TNF-alpha found in arthritic rats were found to be significantly restored back to near normal levels by the extract in experimental animals. The membrane stabilizing activity of the extract was further evidenced by histological observations made on the limb tissue. Recently, we have reported the presence of many biologically active phyto chemicals such as triterpenes, tannins, anthroquinones, flavonoids, saponins, steroids, resins, lectins, glycosides, sugars, phenolic compounds, and alkaloids in the extract of C. gynandra and these compounds might be responsible for the anti-arthritic properties observed in the present study. The possible mechanism of action of the C. gynandra extract may be through its stabilizing action on lysosomal membranes and there by preventing the spread of inflammation. PMID- 17276571 TI - Human constitutive androstane receptor mediated methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1). AB - Sulfotransferases (SULTs) catalyzed sulfation is important in the regulation of biological activities of hormones and neurotransmitters, the metabolism of drugs, and the detoxification of xenobiotic toxicants. Sulfation also leads to the bioactivation of procarcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) is a major SULT catalyzing the sulfation of hydroxysteroids and xenobiotic alcohols. Our previous studies had shown that the anti-folate drug methotrexate (MTX) can up-regulate several major isoforms of human SULTs. To determine the mechanisms controlling the regulation of hSULT2A1, the 5'-flanking region of hSULT2A1 was constructed into the pGL3-Basic luciferase reporter vector. The transcriptional regulation mechanism of hSULT2A1 promoter was studied using Caco-2 cell line based on the reporter gene assay. Nuclear receptor co transfection results indicated that human constitutive androstane receptor (hCAR) and human retinoid X receptor alpha (hRXRalpha) were involved in the transcriptional regulation of hSULT2A1. RNA interference experiments further proved the role of hCAR in hSULT2A1 regulation. Progressive promoter deletion, DNA sequence alignment, and site directed promoter mutation results suggested that an imperfect inverted repeat DNA motif, IR2 (-186AGCTCAGATGACCC-173), within the hSULT2A1 promoter region mediated the hSULT2A1 induction by MTX. Furthermore, electrophoretic mobility shift assay and super shift assay were employed to characterize the interactions of hCAR and hRXRalpha with the IR2 element. In summary, we identified an IR2 DNA cis-element located at -186/-173 of hSULT2A1 promoter region; the IR2 element mediates the MTX induction of hSULT2A1 through interacting with hCAR and hRXRalpha. PMID- 17276573 TI - Direct inhibition of endothelial nitric oxide synthase by hydrogen sulfide: contribution to dual modulation of vascular tension. AB - We characterized actions of hydrogen sulfide (H(2)S) on tension of isolated rat and mouse aortae, and then examined if H(2)S could directly modulate activity of endothelial nitric oxide (NO) synthase (eNOS). Isometric tension was recorded in rat and mouse aortic rings. Activity of recombinant bovine eNOS was determined as conversion of [(3)H]-arginine into [(3)H]-citrulline. NaHS, a H(2)S donor, caused contraction at low concentrations and relaxation at high concentrations in both rat and mouse aortae precontracted with phenylephrine. The contractile and relaxant effects of NaHS were enhanced and partially blocked, respectively, by the K(+)(ATP) channel inhibitor glibenclamide in the rat, but not mouse, aortae. In the KCl-precontracted rat aorta, NaHS produced glibenclamide-resistant contraction and relaxation. NaHS produced only relaxation, but not contraction, in the endothelium-denuded aortae, and also in the endothelium-intact aortae in the presence of inhibitors of NOS or soluble guanylate cyclase. NaHS pretreatment greatly attenuated the relaxation induced by acetylcholine, but not by an NO donor, in the tissues. Finally, we found that NaHS inhibited the conversion of [(3)H]-arginine into [(3)H]-citrulline by recombinant eNOS. NaHS thus causes contraction and relaxation in rat and mouse aortae. K(+)(ATP) channels are considered to contribute only partially to the NaHS-evoked relaxation. Most interestingly, our data demonstrate direct inhibition of eNOS by NaHS, probably responsible for its contractile activity, being evidence for a novel function of H(2)S. PMID- 17276572 TI - Characterization of WIF-B9/R cells as an in vitro model with hepatocyte-like polarity and enhanced expression of canalicular ABC transporters involved in phase III of hepatic detoxification. AB - The rat hepatoma/human fibroblast hybrid cell line WIF-B9 was developed to be used in studies requiring maintained hepatocyte-like polarity. To enhance their usefulness in order to investigate hepatic phase III detoxification process, we have characterized a subline of WIF-B9 cells (WIF-B9/R) obtained by exposure to progressively increasing cisplatin concentrations (up to 10 microM) and double sub-clonal selection. As compared to WIF-B9 cells, the cytostatic effect of cisplatin and doxorubicin on WIF-B9/R cells was lower (>10-fold), whereas the ability to reduce cell loading of cisplatin, doxorubicin, rhodamine 123 and calcein was higher. As their parent cells, WIF-B9/R cells express hepatocyte-like polarity. However, they have enhanced stable expression of Mdr1, Mrp1, Mrp2, Mrp3 and BCRP, but not Bsep/BSEP, as determined by real-time quantitative RT-PCR and western blot. Differentiation to hepatocyte-like phenotype was characterized by the formation of canalicular-like structures, containing in their membranes immunocytochemically detectable Mdr1, Mrp2 and BCRP. Functionality of these ABC transporters was evaluated by using specific substrates and inhibitors. Thus, canalicular-like structures were able to concentrate calcein, rhodamine 123 and doxorubicin. Moreover, verapamil, probenecid and Hoechst-33342 inhibited doxorubicin efflux and enhanced its content in WIF-B9/R cells. Probenecid inhibited calcein efflux and increased calcein cell load, but had no effect on cell loading of rhodamine 123, which was increased by verapamil and Hoechst 33342. In conclusion, WIF-B9/R cells are a useful model of polarized cells to study, in the absence of Bsep/BSEP, hepatic phase III of the detoxification process of several compounds whose canalicular transport is mediated by ABC proteins. PMID- 17276574 TI - The action of the bacterial toxin, microcin B17, on DNA gyrase. AB - Microcin B17 (MccB17) is a peptide-based bacterial toxin that targets DNA gyrase, the bacterial enzyme that introduces supercoils into DNA. The site and mode of action of MccB17 on gyrase are unclear. We review what is currently known about MccB17-gyrase interactions and summarise approaches to understanding its mode of action that involve modification of the toxin. We describe experiments in which treatment of the toxin at high pH leads to the deamidation of two asparagine residues to aspartates. The modified toxin was found to be inactive in vivo and in vitro, suggesting that the Asn residues are essential for activity. Following on from these studies we have used molecular modelling to suggest a 3D structure for microcin B17. We discuss the implications of this model for MccB17 action and investigate the possibility that it binds metal ions. PMID- 17276575 TI - Quality of closed chest compression in ambulance vehicles, flying helicopters and at the scene. AB - CONTEXT: Transport of patients during resuscitation is a critical procedure. In both, ambulances and helicopters the quality of resuscitation is potentially hampered due to the movement of the vehicle and confined space. To date, however, no direct comparison of the quality of resuscitation at the scene, during a helicopter flight and in a moving ambulance has been made. OBJECTIVE: Direct comparison of the quality of resuscitation at the scene, during a helicopter flight and in a moving ambulance. DESIGN: The study was performed in July 2005 as a randomised cross-over trial comparing different environments for resuscitation. SETTING: Medical University of Vienna. PARTICIPANTS: Eleven European Resuscitation Council (ERC) approved health care professionals. INTERVENTIONS: Interventions during resuscitation: (a) in a moving ambulance, (b) in a flying helicopter, were compared to those staying at the (c) scene (control). Each participant performed resuscitation in all three environments. MAIN OUTCOME MEASURES: Quality of chest compression during resuscitation. RESULTS: Compared to resuscitation at the scene, efficiency of chest compressions during a helicopter flight was 86% and 95% in the moving ambulance 95%. There were no differences in secondary outcomes (time without chest compression, total number of incorrect hand position relative to total compressions, and total number of incorrect pressure release relative to total compressions). CONCLUSIONS: Resuscitation during transport is feasible and relatively efficient. There is some difference between the environments, but there is no relevant difference between helicopters and ambulances regarding the effectiveness of CPR. PMID- 17276577 TI - Regulating overabundant ungulate populations: an example for elk in Rocky Mountain National Park, Colorado. AB - In many areas of the world, populations of native ungulates have become so abundant that they are believed to be harming vegetation and disrupting ecosystem function. Methods for controlling overabundance populations include culling animals from the population and controlling fertility using contraceptives. However, understanding the feasibility these alternatives requires insight into their long-term effects on populations. We constructed a simulation model to evaluate options for regulating elk populations in and around Rocky Mountain National Park and used the model to compare different treatment options. Methods were evaulated with respect to the time required to reduce the population to a target level, the number of animals treated and/or culled and the risk of extinction. We contrasted culling with lifetime-effect contraceptives and yearlong contraceptives. Lifetime contraceptives required treating the fewest animals to maintain the population at desired targets. However, this approach also causes the greatest population variability and potential risk of extinction. Yearlong contraceptives required treatment of dramatically more animals but had essentially no extinction risk whereas culling produced intermediate levels of both extinction risk and number of animals treated. These results characterize the risks and benefits of alternative control strategies for overabundant wildlife. They emerge from a modeling approach that can be broadly useful in helping managers in choose between alternatives for regulating overabundant wildlife. PMID- 17276576 TI - The endocannabinoid pathway in Huntington's disease: a comparison with other neurodegenerative diseases. AB - Endocannabinoids are endogenous agonists of cannabinoid receptors, and comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol are the best-studied members of this class of lipid mediators, and it is now widely accepted that their in vivo concentration and biological activity are largely dependent on a "metabolic control." Therefore, the proteins that synthesize, transport and degrade endocannabinoids, and that together with the target receptors form the so called "endocannabinoid system," are the focus of intense research. This new system will be presented in this review, in order to put in a better perspective the impact of its modulation on Huntington's disease. In particular, the effect of agonists/antagonists of endocannabinoid receptors, or of inhibitors of endocannabinoid metabolism, will be discussed in the context of onset and progression of Huntington's disease, and will be compared with other neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, and amyotropic lateral sclerosis. Also the plastic changes of endocannabinoids in multiple sclerosis will be reviewed, as a paradigm of their impact in neuroinflammatory disorders. PMID- 17276578 TI - Economic and policy instrument analyses in support of the scrap tire recycling program in Taiwan. AB - Understanding the cost-effectiveness and the role of economic and policy instruments, such as the combined product tax-recycling subsidy scheme or a tradable permit, for scrap tire recycling has been of crucial importance in a market-oriented environmental management system. Promoting product (tire) stewardship on one hand and improving incentive-based recycling policy on the other hand requires a comprehensive analysis of the interfaces and interactions in the nexus of economic impacts, environmental management, environmental valuation, and cost-benefit analysis. This paper presents an assessment of the interfaces and interactions between the implementation of policy instruments and its associated economic evaluation for sustaining a scrap tire recycling program in Taiwan during the era of the strong economic growth of the late 1990s. It begins with an introduction of the management of the co-evolution between technology metrics of scrap tire recycling and organizational changes for meeting the managerial goals island-wide during the 1990s. The database collected and used for such analysis covers 17 major tire recycling firms and 10 major tire manufacturers at that time. With estimates of scrap tire generation and possible scale of subsidy with respect to differing tire recycling technologies applied, economic analysis eventually leads to identify the associated levels of product tax with respect to various sizes of new tires. It particularly demonstrates a broad perspective of how an integrated econometric and engineering economic analysis can be conducted to assist in implementing policy instruments for scrap tire management. Research findings indicate that different subsidy settings for collection, processing, and end use of scrap tires should be configured to ameliorate the overall managerial effectiveness. Removing the existing boundaries between designated service districts could strengthen the competitiveness of scrap tires recycling industry, helping to reduce the required levels of product tax and subsidy. With such initial breakthroughs at hand to handle the complexity of scrap tire recycling technologies, there remains unique management and policy avenues left to explore if a multi-dimensional solution is to be successful in the long run. PMID- 17276579 TI - Prenatal detection of fetal growth restriction by fetal femur volume: efficacy assessment using three-dimensional ultrasound. AB - As fetal growth restriction (FGR) may have increased risks with perinatal morbidity and mortality, it is very important to detect FGR prenatally. Fetal femur dysplasia is associated with a variety of congenital syndromes and FGR as well. To date, no prenatal assessment of fetal FV in predicting FGR using three dimensional (3D) ultrasound (US) has been reported. In this study, we used 3D US to test the efficacy of fetal femur volume (FV) measurement in predicting FGR. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and efficacy of fetal FV assessed by 3D US in detecting FGR according to the Bayes' theorem. All the fetuses were singletons and were followed up to delivery to determine whether they were complicated with FGR or not. In total, 304 fetuses without FGR and 42 fetuses with FGR were included for FV assessment in utero by 3D US. Our results showed fetal FV assessed by 3D US can differentiate fetuses with FGR from fetuses without FGR well. The best predicting threshold for FGR is at the 10th percentile of FV. Using the 10th percentile as the cutoff, the sensitivity of fetal FV in predicting FGR was 71.4%, specificity 94.1%, positive predictive value 62.5%, negative predictive value 96.0% and accuracy 91.3%. In addition, fetal FV is superior to fetal biparietal diameter and fetal abdominal circumference in predicting FGR. In conclusion, fetal FV assessed by 3D US can be applied to detect FGR well prenatally. We believe fetal FV assessment by 3D US would be a useful test in detecting fetuses with FGR. PMID- 17276580 TI - The Actifetus system: a multidoppler sensor system for monitoring fetal movements. AB - Fetal heart rate (FHR) monitoring is a crucial part of monitoring at-risk pregnancies and labor. Its aim is to detect any abnormalities that might indicate acute fetal distress and a need for rapid treatment to avoid death or serious sequelae, including cerebral handicap. The use of fetal biophysical profiles in high-risk pregnancies (gravidic hypertension, in utero infection, etc.) helps to distinguish healthy fetuses from those with chronic conditions. Fetal biophysical profile scores have been developed that integrate five biophysical parameters, one of which is derived from the FHR. The major parameters detected are the rate of fetal movements, fetal tone, fetal breathing movement and amniotic fluid volume. All of those parameters except FHR are obtained by prolonged echographic observation and cannot be used routinely. We developed in this study a new multigate multitransducer pulsed Doppler system for survey of fetal behavior. Fast Fourier transform and autocorrelation function have been used for processing and analyzing ultrasonic Doppler signals generated by fetal movements. Several parameters are analyzed in each of the 12 x 5 = 60 Doppler gates: amplitude of signals reflected by moving fetal structures, velocity, direction and amplitude of displacement of fetal structure (heart, chest, limbs). From these parameters it is possible to calculate FHR and characterize fetal activity. Preliminary in vivo results obtained in 15 pregnant women (30 to 36 wk) are very encouraging but they have yet to be confirmed in future studies. These results also demonstrate the advantages of transducers designed for improved fetal movement detection. The algorithms needs to be precise enough to allow the Actifetus system to function in real time. We now have at our disposal some algorithms that succeed in quantifying FHR and fetal movements with a signal from a given sensor at a given depth. This study confirms the feasibility of monitoring fetal movements by the Actifetus system and demonstrates the importance of the characterization of fetal rhythms (and fetal behavior). The Actifetus system will serve as a new mean for studying fetal response to environment and detecting anomalies related to fetal suffering. PMID- 17276582 TI - Editorial comment on: the relationship between objective frequency-volume chart data and the I-PSS in men with lower urinary tract symptoms. PMID- 17276583 TI - The relationship between objective frequency-volume chart data and the I-PSS in men with lower urinary tract symptoms. AB - OBJECTIVE: The International Prostate Symptom Score (I-PSS) is considered a benchmark in defining the severity of lower urinary tract symptoms (LUTS). However, its relationship with variables of the frequency-volume (FV) chart, an objective measure of LUTS, is not well understood. We analyzed this relationship between the I-PSS and FV chart variables in men with LUTS. METHODS: Patients referred for the investigation of uncomplicated LUTS completed an I-PSS and a 3-d FV chart. Correlation coefficients were used to describe the relationship between total I-PSS and its components with the FV variables. The distributions of FV variable scores within the categories of I-PSS severity were also examined. The effect of patient's quality of life score on I-PSS and FV variables was analyzed using regression. RESULTS: A total of 104 patients completed both the I-PSS and FV chart. The association between FV variables and I-PSS scores was generally weak, with 24-h frequency being the strongest (r = 0.43) and with considerable overlap within each severity category. There was weak association between the I PSS for nocturia and urgency and their FV counterparts. The number of self reported nocturnal voids tended to be overestimated. These discrepancies were partly explained by the patient's quality of life rating, which reduced the level of variation between I-PSS score and FV variables and accounted for some of the overestimation. CONCLUSION: Weak associations were found between the self-rated I PSS scores and FV measures of voiding, suggesting that the accurate assessment of LUTS requires self-reported measures of symptoms and objective measures of voiding behaviour. Significant differences between the two types of data might be explained by perceived quality of life. PMID- 17276584 TI - Pattern storage in a sparsely coded neural network with cyclic activation. AB - We investigate an artificial neural network model with a modified Hebb rule. It is an auto-associative neural network similar to the Hopfield model and to the Willshaw model. It has properties of both of these models. Another property is that the patterns are sparsely coded and are stored in cycles of synchronous neural activities. The cycles of activity for some ranges of parameter increase the capacity of the model. We discuss basic properties of the model and some of the implementation issues, namely optimizing of the algorithms. We describe the modification of the Hebb learning rule, the learning algorithm, the generation of patterns, decomposition of patterns into cycles and pattern recall. PMID- 17276585 TI - Single molecule FRET for the study on structural dynamics of biomolecules. AB - Single molecule fluorescence resonance energy transfer (FRET) is the technique that has been developed by combining FRET measurement and single molecule fluorescence imaging. This technique allows us to measure the dynamic changes of the interaction and structures of biomolecules. In this study, the validity of the method was tested using fluorescence dyes on double stranded DNA molecules as a rigid spacer. FRET signals from double stranded DNA molecules were stable and their average FRET values provided the distance between the donor and acceptor in agreement with B-DNA type helix model. Next, the single molecule FRET method was applied to the studies on the dynamic structure of Ras, a signaling protein. The data showed that Ras has multiple conformational states and undergoes transition between them. This study on the dynamic conformation of Ras provided a clue for understanding the molecular mechanism of cell signaling switches. PMID- 17276586 TI - New structural variation in evolutionary searches of RNA neutral networks. AB - RNA secondary structure is an important computational model to understand how genetic variation maps into phenotypic (structural) variation. Evolutionary innovation in RNA structures is facilitated by neutral networks, large connected sets of RNA sequences that fold into the same structure. Our work extends and deepens previous studies on neutral networks. First, we show that even the 1 mutant neighborhood of a given sequence (genotype) G0 with structure (phenotype) P contains many structural variants that are not close to P. This holds for biological and generic RNA sequences alike. Second, we analyze the relation between new structures in the 1-neighborhoods of genotypes Gk that are only a moderate Hamming distance k away from G0, and the structure of G0 itself, both for biological and for generic RNA structures. Third, we analyze the relation between mutational robustness of a sequence and the distances of structural variants near this sequence. Our findings underscore the role of neutral networks in evolutionary innovation, and the role that high robustness can play in diminishing the potential for such innovation. PMID- 17276587 TI - Modelling of syntactical processing in the cortex. AB - Probably the hardest test for a theory of brain function is the explanation of language processing in the human brain, in particular the interplay of syntax and semantics. Clearly such an explanation can only be very speculative, because there are essentially no animal models and it is hard to study detailed neural processing in humans. The approach presented in this paper uses well established basic neural mechanisms in a plausible global network architecture that is formulated essentially in terms of cortical areas and their intracortical and corticocortical interconnections. The neural implementation of this system shows that the comparatively intricate logical task of understanding semantico syntactical structures can be mastered by a neural network architecture. The system presented also shows additional context awareness, in particular the model is able to correct ambiguous input to a certain degree, e.g. the input "bot show/lift green wall" with an artificial ambiguity between "show" and "lift" is correctly interpreted as "bot show green wall" since a wall is not liftable. Furthermore, the system is able to learn new object words during runtime. PMID- 17276588 TI - Interaction between CD44 and hyaluronate induces chemoresistance in non-small cell lung cancer cell. AB - CD44s is a principle hyaluronate (HA) receptor and has been reported to play an important role in cancer cell invasion and metastasis. The aim of our study is to determine if the interaction between HA and CD44s influences in vitro chemosensitivity of non-small cell lung cancer (NSCLC). NSCLC cell line, H322 cells, transfected with the CD44s gene (H322/CD44s) cultured on HA coated plates were more resistant to cisplatin (CDDP) than that on bovine serum albumin. Multidrug resistance protein2 (MRP2) expression was induced in H322/CD44s cells cultured on HA. MRP2 inhibitor, MK571, not only suppressed MRP2 expression but also reversed CDDP resistance. These results suggest that the interaction between CD44s and HA play a pivotal role in acquired resistance to CDDP in NSCLC and MRP2 could be involved in this potential mechanism. PMID- 17276589 TI - Hsp27, Hsp70 and mismatch repair proteins hMLH1 and hMSH2 expression in peripheral blood lymphocytes from healthy subjects and cancer patients. AB - Mismatch repair (MMR) deficiency and higher expression levels of heat shock proteins (Hsps) have been implicated with drug resistance to topoisomerase II poisons (doxorubicin) and to platinum compounds (cisplatin). This study was designed to determine individual influences of doxorubicin and cisplatin treatment on the expression of Hsp27, Hsp70, hMLH1 and hMSH2 proteins and in the DNA damage status in peripheral blood lymphocytes (PBLs). In addition, we studied whether these proteins and the DNA damage correlated with the survival of cancer patients. PBLs from 10 healthy donors and 25 cancer patients (before and after three cycles of chemotherapy) were exposed to in vitro treatments: C (control), HS (heat shock at 42 degrees C), Do or Pt (doxorubicin or cisplatin alone), and HS+Do or HS+Pt (heat shock+doxorubicin or heat shock+cisplatin). PBLs were collected at time 0 (T0: immediately after drug treatment) and after 24h of repair (T24). Hsp27, Hsp70, hMLH1 and hMSH2 were studied by immunocytochemistry and the DNA damage by alkaline comet assay. Immunofluorescence studies and confocal microscopy revealed that hMLH1 and hMSH2 colocalized with Hsp27 and Hsp72 (inducible form of Hsp70). hMLH1 and hMSH2 were significantly induced by Pt and HS+Pt at T24 in cancer patients, but only modestly influenced by Do. Cancer patients presented higher basal expression of total and nuclear Hsp27 and Hsp70 than controls, and these proteins were also increased by HS, Do and HS+Do. The Hsp70 induction by Pt and HS+Pt was noted in cancer patients, especially nuclear Hsp70. In cancer patients, basal DNA damage was slightly higher than in healthy persons; and after Pt and HS+Pt treatments, DNA migration and number of apoptotic cells were higher than controls. Hsps accomplished a cytoprotective function in pre-chemotherapy PBLs (HS before Do or Pt), but not in post-chemotherapy samples. In Pt-treated patients the ratio N/C (nuclear/cytoplasmic) of Hsp27 was related to disease free survival and overall survival, and hMSH2 correlated with overall survival. The results point to the utility of these molecules and of the comet assay as possible predictive markers. PMID- 17276590 TI - Human esophageal cancer endothelial cells increase tumor growth by incorporating with mouse endothelium. AB - Current in vivo investigations of tumor angiogenesis mainly rely on the results obtained from engrafted models in mice. In the present study, we attempt to assess the potential of human tumor endothelium to form neovasculature in different engrafted tumor models. The tumor endothelial cells were isolated from human esophageal squamous cell carcinoma, and then identified by anti-VEGFR1/2 immunoreactions and tube formation assay. Esophageal and lung cancer cells were subcutaneously inoculated into nude mice with human esophageal cancer endothelial cells (HECECs), respectively. The human umbilical vein endothelial cells (HUVECs) were also co-inoculated into mice with esophageal cancer cells as a control. The engrafted tumor growth was significantly promoted by co-inoculation of HECECs in comparison with injection of esophageal tumor cells alone. Immunohistochemistry of anti-CD31 and anti-huCD31 was performed to detect the micro-vessels in the engrafted tumors which revealed that the HECECs formed humanized micro-vessels and significantly increased the micro-vessel density in engrafted tumors comparing with the tumors without HECECs. However, HUVEC cells could not enhance the esophageal tumor growth and the growth of lung tumors could not be increased by HECECs, either. Few humanized blood vessels were found in these two groups of xenografts. These results suggest that the specific interaction between HECECs and esophageal tumor cells contributes to the neovasculature construction and esophageal tumor growth in xenografts. PMID- 17276591 TI - A methodology for the quantitative risk assessment of major accidents triggered by seismic events. AB - A procedure for the quantitative risk assessment of accidents triggered by seismic events in industrial facilities was developed. The starting point of the procedure was the use of available historical data to assess the expected frequencies and the severity of seismic events. Available equipment-dependant failure probability models (vulnerability or fragility curves) were used to assess the damage probability of equipment items due to a seismic event. An analytic procedure was subsequently developed to identify, evaluate the credibility and finally assess the expected consequences of all the possible scenarios that may follow the seismic events. The procedure was implemented in a GIS-based software tool in order to manage the high number of event sequences that are likely to be generated in large industrial facilities. The developed methodology requires a limited amount of additional data with respect to those used in a conventional QRA, and yields with a limited effort a preliminary quantitative assessment of the contribution of the scenarios triggered by earthquakes to the individual and societal risk indexes. The application of the methodology to several case-studies evidenced that the scenarios initiated by seismic events may have a relevant influence on industrial risk, both raising the overall expected frequency of single scenarios and causing specific severe scenarios simultaneously involving several plant units. PMID- 17276592 TI - Chemical constituents in particulate emissions from an integrated iron and steel facility. AB - Particle emissions from four integrated iron and steel plant processes, i.e., coke making, sintering, cold forming, and hot forming, were investigated in this study. Particle compositions of 21 element species, 11 ionic species, elemental carbon (EC), organic carbon (OC) and 16 polyaromatic hydrocarbons (PAHs) were analyzed to create "fingerprints" of the particles emitted from various processes in an integrated iron and steel plant. Results indicated that element compositions (0.11-0.42 g/g), water-soluble ions (0.34-0.52 g/g), elemental carbon (0.008-0.14 g/g), organic carbon (0.02-0.06 g/g) and PAHs (0.52-6.2 mg/g) contributed to the particle mass. In general, sulfur had a higher mass contribution than the other elements, which resulted from the use of coal, flux, heavy oil, and many recycled materials in the iron and steel plant. The particle mass contribution of potassium and chlorine in the sinter plant was higher than in other processes; this may be attributed to the lower boiling point and volatility of potassium. In addition, many recycled materials were fed into the sinter plant, causing a high concentration of potassium and chlorine in the particle phase. Eight PAH compounds were analyzed in the four processes. The carcinogenic compound Benzo(a)pyrene (BaP) was detectable only in the sintering process. PMID- 17276593 TI - Mathematical models applied to the Cr(III) and Cr(VI) breakthrough curves. AB - Trivalent and hexavalent chromium continuous biosorption was studied using residual brewer Saccharomyces cerevisiae immobilized in volcanic rock. The columns used in the process had a diameter of 4.5 cm and a length of 140 cm, working at an inlet flow rate of 15 mL/min. Breakthrough curves were used to study the yeast biosorption behavior in the process. The saturation time (ts) was 21 and 45 h for Cr(III) and Cr(VI), respectively, and a breakthrough time (tb) of 4 h for Cr(III) and 5 h for Cr(VI). The uptake capacity of the biosorbent for Cr(III) and Cr(VI) were 48 and 60 mg/g, respectively. Two non-diffusional mathematical models with parameters t0 and sigma were used to adjust the experimental data obtained. Microsoft Excel tools were used for the mathematical solution of the two parameters used. PMID- 17276594 TI - Modeling of adsorption isotherms of phenol and chlorophenols onto granular activated carbon. Part I. Two-parameter models and equations allowing determination of thermodynamic parameters. AB - The adsorption equilibrium isotherms of five phenolic compounds from aqueous solutions onto granular activated carbon (GAC) were studied and modeled. Phenol (Ph), 2-chlorophenol (2-CP), 4-chlorophenol (4-CP), 2,4-dichlorophenol (DCP), and 2,4,6-trichlorophenol (TCP) were chosen for the adsorption tests. To predict the adsorption isotherms and to determine the characteristic parameters for process design, seven isotherm models: Langmuir (five linear forms), Freundlich, Elovich, Temkin, Fowler-Guggenheim, Kiselev, and Hill-de Boer models were applied to experimental data. The results reveal that the adsorption isotherm models fitted the data in the order: Fowler-Guggenheim>Hill-de Boer>Temkin>Freundlich>Kiselev>Langmuir isotherms. Adsorption isotherms modeling shows that the interaction of phenolic compounds with activated carbon surface is localized monolayer adsorption, that is adsorbed molecules are adsorbed at definite, localized sites. Each site can accommodate only one molecule. The interaction among adsorbed molecules is repulsive and there is no association between them, adsorption is carried out on energetically different sites and is an exothermic process. Uptake of phenols increases in the order Ph<2-CP<4 CP10 Gy by allowing the PTV to be underdosed in such a way that the radiobiological model predicts a decrease in subclinical disease control probability of (typically) 1% to a few percent. CONCLUSION: The trade-off between parotid gland sparing and underdosages in the PTV has been quantified by the use of an alternative method to present dose-volume information and by the use of a radiobiological model to predict subclinical disease control probability. PMID- 17276610 TI - Academic career selection and retention in radiation oncology: the Joint Center for Radiation Therapy experience. AB - PURPOSE: The United States healthcare system has witnessed declining reimbursement and increasing documentation requirements for longer than 10 years. These have decreased the time available to academic faculty for teaching and mentorship. The impact of these changes on the career choices of residents is unknown. The purpose of this report was to determine whether changes have occurred during the past decade in the proportion of radiation oncology trainees from a single institution entering and staying in academic medicine. METHODS AND MATERIALS: We performed a review of the resident employment experience of Harvard Joint Center for Radiation Therapy residents graduating during 13 recent consecutive years (n = 48 residents). The outcomes analyzed were the initial selection of an academic vs. nonacademic career and career changes during the first 3 years after graduation. RESULTS: Of the 48 residents, 65% pursued an academic career immediately after graduation, and 44% remained in academics at the last follow-up, after a median of 6 years. A later graduation year was associated with a decrease in the proportion of graduates immediately entering academic medicine (odds ratio, 0.78; 95% confidence interval, 0.65-0.94). However, the retention rate at 3 years of those who did immediately enter academics increased with a later graduation year (p = 0.03). CONCLUSION: During a period marked by notable changes in the academic healthcare environment, the proportion of graduating Harvard Joint Center for Radiation Therapy residents pursuing academic careers has been declining; however, despite this decline, the retention rates in academia have increased. PMID- 17276612 TI - Low-dose radiotherapy as a chemopotentiator of gemcitabine in tumors of the pancreas or small bowel: a phase I study exploring a new treatment paradigm. AB - PURPOSE: To determine the maximum tolerated dose of upper abdominal low-dose fractionated radiotherapy (<1.0 Gy per fraction) given in combination with, and as a chemopotentiator for, gemcitabine. METHODS AND MATERIALS: Gemcitabine was given at 1,250 mg/m(2) at 10 mg/m(2)/min on Days 1 and 8 of a 3-week cycle. Low dose fractionated radiotherapy was tested at two dose levels: 60 cGy per fraction and 70 cGy per fraction. Radiotherapy was given b.i.d. on Days 1, 2, 8, and 9. Four cycles were planned. RESULTS: Twenty-seven patients have been put on study. Ten patients have been entered in Phase I: 6 with metastatic/recurrent pancreatic carcinoma and 4 with unresectable pancreatic/small bowel carcinoma. Two of four patients at Dose Level 2 experienced dose-limiting toxicity. The overall radiographic response was 30%, and median survival was 11 months (range, 4-37 months). CONCLUSION: Low-dose fractionated radiotherapy to the upper abdomen is well tolerated at 60 cGy per fraction when combined with gemcitabine. Phase II evaluation is ongoing. PMID- 17276613 TI - The failure patterns of oral cavity squamous cell carcinoma after intensity modulated radiotherapy-the university of iowa experience. AB - PURPOSE: Determine the failure patterns of oral cavity squamous cell carcinoma (SCC) treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between May 2001 and July 2005, 55 patients with oral cavity SCC were treated with IMRT for curative intent. Forty-nine received postoperative IMRT, 5 definitive IMRT, and 1 neoadjuvant. Three target volumes were defined (clinical target CTV1, CTV2, and CTV3). The failure patterns were determined by coregistration or comparison of the treatment planning computed tomography to the images obtained at the time of recurrence. RESULTS: The median follow-up for all patients was 17.1 months (range, 0.27-59.3 months). The median follow-up for living patients was 23.9 months (range, 9.3-59.3 months). Nine patients had locoregional failures: 4 local failures only, 2 regional failures only, and 3 had both local and regional failures. Five patients failed distantly; of these, 3 also had locoregional failures. The 2-year overall survival, disease-specific survival, local recurrence-free survival, locoregional recurrence-free survival, and distant disease-free survival was 68%, 74%, 85%, 82%, and 89%, respectively. The median time from treatment completion to locoregional recurrence was 4.1 months (range, 3.0-12.1 months). Except for 1 patient who failed in contralateral lower neck outside the radiation field, all failed in areas that had received a high dose of radiation. The locoregional control is strongly correlated with extracapsular extension. CONCLUSIONS: Intensity-modulated RT is effective for oral cavity SCC. Most failures are in-field failures. Further clinical studies are necessary to improve the outcomes of patients with high-risk features, particularly for those with extracapsular extension. PMID- 17276614 TI - Adjuvant concurrent chemoradiation for adenocarcinoma of the distal common bile duct. AB - PURPOSE: To examine the effect of adjuvant chemoradiation for adenocarcinoma of the distal common bile duct (DCBD) after pancreaticoduodenectomy (PD) on local control and survival. METHODS AND MATERIALS: A total of 34 cases of adenocarcinoma of the DCBD were treated with PD and adjuvant chemoradiation at Johns Hopkins Hospital between 1994 and 2003. Median radiation dose was 5,040 cGy (range, 4,000-5,400 cGy). Concurrent 5-fluorouracil-based chemotherapy was given with radiation therapy, followed by maintenance chemotherapy. RESULTS: The median follow-up of patients alive at the time of analysis was 41 months. Death occurred in 21 of 34 patients (62%) during the follow-up period, all from progressive, distant metastatic disease. Median overall survival was 36.9 months, with a 5 year survival of 35%. On multivariate analysis, only nodal status significantly predicted survival (p < 0.02). For patients with negative and positive lymph nodes, 5-year survival was 100% and 24%, respectively. Actuarial 5-year local control was 70%. Compared with historical controls who underwent PD alone, patients who underwent surgery and adjuvant chemoradiation had significantly longer survival (36.9 months vs. 22 months; p < 0.05). Overall survival was significantly longer for both lymph node negative and lymph node positive patients (p < 0.05). CONCLUSIONS: Adjuvant chemoradiation after PD for adenocarcinoma of the DCBD may improve local control and overall survival. The predominant mode of failure is distant metastatic disease, highlighting the need for improved systemic therapy. PMID- 17276615 TI - Relationships between rectal wall dose-volume constraints and radiobiologic indices of toxicity for patients with prostate cancer. AB - PURPOSE: The purpose of this article was to investigate how exceeding specified rectal wall dose-volume constraints impacts on the risk of late rectal bleeding by using radiobiologic calculations. METHODS AND MATERIALS: Dose-volume histograms (DVH) of the rectal wall of 250 patients with prostate cancer were analyzed. All patients were treated by three-dimensional conformal radiation therapy, receiving mean target doses of 80 Gy. To study the main features of the patient population, the average and the standard deviation of the distribution of DVHs were generated. The mean dose , generalized equivalent uniform dose formulation (gEUD), modified equivalent uniform dose formulation (mEUD)(0), and normal tissue complication probability (NTCP) distributions were also produced. The DVHs set was then binned into eight classes on the basis of the exceeding or the fulfilling of three dose-volume constraints: V(40) = 60%, V(50) = 50%, and V(70) = 25%. Comparisons were made between them by , gEUD, mEUD(0), and NTCP. RESULTS: The radiobiologic calculations suggest that late rectal toxicity is mostly influenced by V(70). The gEUD and mEUD(0) are risk factors of toxicity always concordant with NTCP, inside each DVH class. The mean dose, although a reliable index, may be misleading in critical situations. CONCLUSIONS: Both in three-dimensional conformal radiation therapy and particularly in intensity modulated radiation therapy, it should be known what the relative importance of each specified dose-volume constraint is for each organ at risk. This requires a greater awareness of radiobiologic properties of tissues and radiobiologic indices may help to gradually become aware of this issue. PMID- 17276616 TI - A dosimetric evaluation of conventional helmet field irradiation versus two-field intensity-modulated radiotherapy technique. AB - PURPOSE: To compare dosimetric differences between conventional two-beam helmet field irradiation (external beam radiotherapy, EBRT) of the brain and a two-field intensity-modulated radiotherapy (IMRT) technique. METHODS AND MATERIALS: Ten patients who received helmet field irradiation at our institution were selected for study. External beam radiotherapy portals were planned per usual practice. Intensity-modulated radiotherapy fields were created using the identical field angles as the EBRT portals. Each brain was fully contoured along with the spinal cord to the bottom of the C2 vertebral body. This volume was then expanded symmetrically by 0.5 cm to construct the planning target volume. An IMRT plan was constructed using uniform optimization constraints. For both techniques, the nominal prescribed dose was 3,000 cGy in 10 fractions of 300 cGy using 6-MV photons. Comparative dose-volume histograms were generated for each patient and analyzed. RESULTS: Intensity-modulated radiotherapy improved dose uniformity over EBRT for whole brain radiotherapy. The mean percentage of brain receiving >105% of dose was reduced from 29.3% with EBRT to 0.03% with IMRT. The mean maximum dose was reduced from 3,378 cGy (113%) for EBRT to 3,162 cGy (105%) with IMRT. The mean percent volume receiving at least 98% of the prescribed dose was 99.5% for the conventional technique and 100% for IMRT. CONCLUSIONS: Intensity modulated radiotherapy reduces dose inhomogeneity, particularly for the midline frontal lobe structures where hot spots occur with conventional two-field EBRT. More study needs to be done addressing the clinical implications of optimizing dose uniformity and its effect on long-term cognitive function in selected long lived patients. PMID- 17276617 TI - Outcome after radiosurgery for brain metastases in patients with low Karnofsky performance scale (KPS) scores. AB - PURPOSE: The objective of this retrospective study was evaluation of the outcome after stereotactic radiosurgery (SRS) in patients with intracranial metastases and poor performance status. METHODS AND MATERIALS: Forty consecutive patients with metastatic brain tumors and Karnofsky performance scale (KPS) scores < or =50 (mean, 43 +/- 8; median, 40) treated with SRS were analyzed. Poor performance status was caused by presence of intracranial metastases in 28 cases (70%) and resulted from uncontrolled extracerebral disease in 12 (30%). RESULTS: Survival after SRS varied from 3 days to 11.5 months (mean, 3.8 +/- 2.9 months; median, 3.3 months). Survival probability constituted 0.50 +/- 0.07 at 3 months and 0.20 +/- 0.05 at 6 months posttreatment. Cause of low KPS score (p = 0.0173) and presence of distant metastases beside the brain (p = 0.0308) showed statistically significant associations with overall survival in multivariate Cox proportional hazards regression analysis. Median survival was 6.0 months if low KPS score was caused by cerebral disease and distant metastases in regions beyond the brain were absent, 3.3 months if low KPS score was caused by cerebral disease and distant metastases in regions beyond the brain were present, and 1.0 month if poor performance status resulted from extracerebral disease. CONCLUSIONS: Identification of the cause of low KPS score (cerebral vs. extracerebral) in patients with metastatic brain tumor(s) may be important for prediction of the outcome after radiosurgical treatment. If poor patient performance status without surgical indications is caused by intracranial tumor(s), SRS may be a reasonable treatment option. PMID- 17276618 TI - Irradiation promotes Akt-targeting therapeutic gene delivery to the tumor vasculature. AB - PURPOSE: To determine whether radiation-induced increases in nitric oxide (NO) production can influence tumor blood flow and improve delivery of Akt-targeting therapeutic DNA lipocomplexes to the tumor. METHODS AND MATERIALS: The contribution of NO to the endothelial response to radiation was identified using NO synthase (NOS) inhibitors and endothelial NOS (eNOS)-deficient mice. Reporter encoding plasmids complexed with cationic lipids were used to document the tumor vascular specificity and the efficacy of in vivo lipofection after irradiation. A dominant-negative Akt gene construct was used to evaluate the facilitating effects of radiotherapy on the therapeutic transgene delivery. RESULTS: The abundance of eNOS protein was increased in both irradiated tumor microvessels and endothelial cells, leading to a stimulation of NO release and an associated increase in tumor blood flow. Transgene expression was subsequently improved in the irradiated vs. nonirradiated tumor vasculature. This effect was not apparent in eNOS-deficient mice and could not be reproduced in irradiated cultured endothelial cells. Finally, we combined low-dose radiotherapy with a dominant negative Akt gene construct and documented synergistic antitumor effects. CONCLUSIONS: This study offers a new rationale to combine radiotherapy with gene therapy, by directly exploiting the stimulatory effects of radiation on NO production by tumor endothelial cells. The preferential expression of the transgene in the tumor microvasculature underscores the potential of such an adjuvant strategy to limit the angiogenic response of irradiated tumors. PMID- 17276619 TI - Predicting outcome of patients with high-grade gliomas after radiotherapy using quantitative analysis of T1-weighted magnetic resonance imaging. AB - PURPOSE: The aim of this study was to test the hypothesis that measuring quantitative changes in signal intensity early after radiotherapy (RT) in the contrast-enhancing tumor rim and nonenhancing core may be a noninvasive marker of early treatment response in patients with high-grade gliomas. METHODS AND MATERIALS: Twenty patients with high-grade gliomas had magnetic resonance imaging (MRI) performed 1 week before RT, during Weeks 1 and 3 of RT, and every 1 to 3 months after RT as part of a clinical prospective study. Regions of interest (ROI) including contrast-enhancing rim, and the nonenhancing core were defined automatically based on a calculated image of post- to precontrast T1-weighted MRI. Pretreatment T1-weighted MRI signal intensity changes were compared with Weeks 1 and 3 RT and 1 and 3 months post-RT MRI. Clinical and MRI parameters were then tested for prediction of overall survival. RESULTS: Regional T1-weighted signal intensity changes in both the contrast-enhancing rim and the nonenhancing core were observed in all patients during Week 1 and Week 3 of RT. Imaging parameters including signal intensity change within the nonenhancing core after Weeks 1 to 2 RT (p = 0.004), Weeks 3 to 4 RT (p = 0.002) and 1 month after completion of RT (p = 0.002) were predictive of overall survival. Using multivariate analysis including RTOG recursive partitioning analysis (RPA) and signal intensity change, only the signal intensity change in the nonenhancing core at 1 month after RT (p = 0.01) retained significance. CONCLUSION: Quantitative measurements of T1-weighted MRI signal intensity changes in the nonenhancing tumor core (using ratios of pre-post values) may provide valuable information regarding early response during treatment and improve our ability to predict posttreatment outcome. PMID- 17276620 TI - Conformal therapy improves the therapeutic index of patients with anal canal cancer treated with combined chemotherapy and external beam radiotherapy. AB - PURPOSE: To evaluate the clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with anal canal cancer, in terms of local control (LC), freedom from relapse (FFR), and overall survival (OS) rates, and to estimate long-term toxicity data. METHODS AND MATERIALS: Sixty historical patients, treated with conventional radiation techniques (C-RT), were used as controls, and 62 consecutive patients were treated with 3D-CRT. Patients treated with 3D-CRT received 54 Gy in 30 fractions delivered continuously, compared with 45-58.9 Gy (median dose, 54 Gy) in a split course in patients treated with C-RT. Chemotherapy consisted of 5-fluorouracil with either mitomycin-C or cis-platinum given concurrently with radiation. Survival curves were performed using the Kaplan-Meier model, and the Cox proportional hazards model was used for multivariate analysis of risk factors. RESULTS: No differences in stage and age distribution were observed between the two groups. Patients treated with 3D-CRT and C-RT had an actuarial 5-year LC rate of 85.1% and 61.1%, respectively (p = 0.0056); the FFR rate was 70.2% and 46.1% (p = 0.0166), and the OS rate was 80.7% and 53.9% (p = 0.0171). In multivariate analysis, factors of significance for LC were nodal (N) status (p < 0.001); for OS, 3D-CRT (p = 0.038), N status (p = 0.011), and T status (p = 0.012); and for FFR, 3D-CRT (p = 0.024) and N status (p < 0.001). CONCLUSION: The use of 3D-CRT allows patients with anal canal cancer to complete radiation and chemotherapy without interruption for toxicity, with significant improvements in LC, FFR, and OS. PMID- 17276622 TI - Effects of under- and overcrowding on exploratory behavior in the elevated plus maze. AB - The present work investigated whether the number of rats housed in a cage affects exploration of an elevated plus-maze. Male Wistar-derived rats were kept 1, 2, 3, 4, 6, 8, 12, 16, or 24 to same size cages either for 1 or 14 days and tested in the elevated plus-maze. Rats kept 6 to a cage were arbitrarily considered controls because this is the housing condition adopted in many laboratories, ours included. In comparison to controls, 1-day housed rats kept 1, 2, 16, and 24 to a cage decreased the percentage of entries into the open arms. Similar decreases were also found in the time spent in the open arms, the only exception being the group with rats kept 16 to a cage which failed to show significant differences from the control group. Fourteen-day housed rats kept 1, 2, 16, or 24 to a cage decreased the percentage of entries and time spent in the open arms. We found plus-maze exploration to be similar in groups in which rats were kept from 4 to 12 to a cage. The present data indicate that anxiogenic effects resulting from under- and overcrowding should be taken into consideration in behavioral studies. PMID- 17276621 TI - The impact of induction chemotherapy and the associated tumor response on subsequent radiation-related changes in lung function and tumor response. AB - PURPOSE: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. METHODS AND MATERIALS: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. RESULTS: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. CONCLUSIONS: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction. PMID- 17276623 TI - Gender differences in injection risk behaviors at the first injection episode. AB - OBJECTIVES: To examine gender differences in drug injection equipment sharing at injecting initiation. METHODS: Young injecting drug users (IDUs) in New York City February 1999-2003 were surveyed about injection risk behaviors and circumstances at initiation. Analyses were gender-stratified and excluded participants who initiated alone. Multiple logistic regression estimated adjusted odds ratios. RESULTS: Participants (n=249) were 66% male and 82% White. Mean initiation age was 19.2; mean years since initiating was 3.0. Women were significantly more likely to cite social network influence as a reason for initiating, to have male and sex partner initiators, and to share injecting equipment than men. Among women, sharing any injection equipment was associated with initiation by a sex partner and having > or =2 people present. Among men, being injected by someone else predicted sharing any injection equipment, while using a legally obtained syringe was protective. CONCLUSIONS: Social persuasion stemming from sexual and/or social relationships with IDUs may increase women's risk of sharing injection equipment at initiation, and consequently, their early parenteral risk of acquiring blood-borne infections. Interventions should focus on likely initiates, especially women in injecting-discordant sex partnerships, and IDUs (potential initiators). PMID- 17276625 TI - Psychiatric predictors of adolescent and young adult drug use and abuse: what have we learned? PMID- 17276624 TI - Using mathematical modeling and control to develop structured treatment interruption strategies for HIV infection. AB - The goal of this article is to suggest that mathematical models describing biological processes taking place within a patient over time can be used to design adaptive treatment strategies. We demonstrate using the key example of treatment strategies for human immunodeficiency virus type-1 (HIV) infection. Although there has been considerable progress in management of HIV infection using highly active antiretroviral therapies, continuous treatment with these agents involves significant cost and burden, toxicities, development of drug resistance, and problems with adherence; these latter complications are of particular concern in substance-abusing individuals. This has inspired interest in structured or supervised treatment interruption (STI) strategies, which involve cycles of treatment withdrawal and re-initiation. We argue that the most promising STI strategies are adaptive treatment strategies. We then describe how biological mechanisms governing the interaction over time between HIV and a patient's immune system may be represented by mathematical models and how control methods applied to these models can be used to design adaptive STI strategies seeking to maintain long-term suppression of the virus. We advocate that, when such mathematical representations of processes underlying a disease or disorder are available, they can be an important tool for suggesting adaptive treatment strategies for clinical study. PMID- 17276626 TI - Difficulties in emotion regulation and impulse control during cocaine abstinence. AB - RATIONALE: Prior research has shown that cocaine dependence is associated with dysfunction of brain systems involved in emotions and motivational states. OBJECTIVES: To examine whether difficulties in emotion regulation are associated with early cocaine abstinence using the recently validated Difficulties in Emotion Regulation Scale (DERS). METHOD: Recently abstinent treatment-seeking cocaine patients (n=60) completed the DERS during their first week of inpatient treatment and at discharge (3-4 weeks later), and scores were compared with community controls (n=50). RESULTS: Compared with controls, cocaine-dependent individuals reported difficulties relating to understanding emotions, managing emotions and impulse control in the first week of abstinence. With continued abstinence, cocaine-dependent individuals showed continued difficulties only in impulse control. CONCLUSION: Cocaine-dependent individuals report emotion regulation difficulties, particularly during early abstinence. Additionally, protracted distress-related impulse control problems suggest potential relapse vulnerability. PMID- 17276627 TI - The absence of DSM-IV nicotine dependence in moderate-to-heavy daily smokers. AB - BACKGROUND: Current theoretical models of nicotine dependence assume a close relationship between use and dependence; however, previous data suggest that many daily smokers fail to develop nicotine dependence. OBJECTIVES: To determine what percentage of daily smokers fail to meet DSM-IV criteria for nicotine dependence within their lifetime, how non-dependence relates to duration and quantity of cigarette use, and whether other tobacco use and/or specific dependence criteria differentiate never-dependent and dependent smokers. METHODS: Cross-sectional data collected via personal interview from a nationally representative sample of 8213 past year daily smokers were analyzed. RESULTS: Approximately 39.4% of daily smokers never reached nicotine dependence. While the probability of remaining non dependent decreased with smoking quantity and duration since the onset of daily smoking, a substantial portion of individuals (37.7%) who reported smoking >or=10 cigarettes per day and began smoking daily >or=10 years prior, remained never nicotine dependent. CONCLUSIONS: The absence of nicotine dependence in heavy daily smokers may result from limitations in the measurement of dependence and/or nicotine exposure. Alternatively, some individuals may be relatively resistant to becoming nicotine dependent despite extensive use. The latter explanation would have important implications for understanding the nature of nicotine dependence. PMID- 17276628 TI - Covalent genomic DNA modification patterns revealed by denaturing gradient gel blots. AB - Several approaches are used to survey genomic DNA methylation patterns, including Southern blot, PCR, and microarray strategies. All of these methods are based on the use of methylation-sensitive isoschizomer restriction enzyme pairs and/or sodium bisulfite treatment of genomic DNA. They have many limitations, including PCR bias, lack of comprehensive assessment of methylated sites, labor-intensive protocols, and/or the need for expensive equipment. Since the presence of 5 methylcytosine alters the melting properties of DNA molecules, denaturing gradient gel blots (DGG blots), a gene scanning technique which detects differences in DNA fragments based on differential melting behavior, were used to examine genomic modification patterns in normal tissues. Variations in melting behavior, observed as restriction fragment melting polymorphisms (RFMPs), were detected in various tissues from single individuals in all human and mouse genes tested, suggesting the presence of widespread differential cell type-specific DNA modification. Additional DGG blot experiments comparing genomic DNA to unmethylated cloned DNA suggested that the melting variants were most likely caused by DNA methylation differences. The results suggest that the use of DGG blots can provide a comprehensive and rapid method for comparing complex in vivo DNA modification patterns in normal adult somatic cells. PMID- 17276629 TI - Role of sialidase in Mycoplasma alligatoris-induced pulmonary fibroblast apoptosis. AB - Mycoplasma alligatoris causes acute lethal cardiopulmonary disease of susceptible hosts. A survey of its genome implicated sialidase and hyaluronidase, synergistic regulators of hyaluronan receptor CD44-mediated signal transduction leading to apoptotic cell death, as virulence factors of M. alligatoris. In this study, after the existence of a CD44 homolog in alligators was established by immunolabeling primary pulmonary fibroblasts with monoclonal antibody IM7 against murine CD44, the sialidase inhibitor 2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA) was used to examine the effects of sialidase on fibroblast apoptosis following in vitro infection with M. alligatoris. While their CD44 expression remained constant, infected cells exhibited morphologic changes characteristic of apoptosis including decreased size, rounding, disordered alpha-tubulin, and nuclear disintegration compared to untreated controls. DANA was a potent, non toxic inhibitor of the sialidase activity, equivalent to about 1mU of Clostridium perfringens Type VI sialidase, expressed by M. alligatoris in the inoculum. Although DANA did not measurably reduce the proportion of infected fibroblasts labeled by a specific ligand of activated caspases, co-incubation with DANA protected (P<0.01) fibroblasts in a concentration-dependent fashion from the M. alligatoris-induced trends toward increased apoptosis receptor CD95 expression, and increased 5-bromo-2'-deoxyuridine incorporation measured in a terminal dUTP nick end-labeling apoptosis assay. In contrast, incubation with 200-fold excess purified C. perfringens sialidase alone did not affect CD95 expression or chromatin integrity, or induce fibroblast apoptosis. From those observations we conclude that interaction of its sialidase with hyaluronidase or another virulence factor(s) is necessary to elicit the pro-apoptotic effects of M. alligatoris infection. PMID- 17276630 TI - Biofilms and their relevance to veterinary medicine. AB - Bacteria are renowned for their ability to tolerate and adapt to a wide range of adverse environmental conditions. The primary mechanism that facilitates these adaptations is thought to be the capacity to form and maintain biofilms. Within a biofilm, bacteria become attached to a surface where they exist in complex communities which are able to interact with each other through intracellular communication and thus rapidly adapt to changing environments. The organisms within biofilms are notorious for their resistance towards the host immune response and antibacterial agents compared to their free-living planktonic counterparts. Consequently, biofilms are of significant importance to both clinical and veterinary science. However, although bacterial infections are widely reported in animals their association with biofilms is rarely discussed. The aim of this review is to look at the characteristics of biofilm infections in humans and to relate this knowledge to veterinary science in order to assess their relevance in this area. PMID- 17276631 TI - In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet. AB - Equine herpesvirus 1 (EHV-1) is an important equine pathogen that causes respiratory disease, abortion, neonatal death and paralysis. Although vaccines are available, they are not fully protective and outbreaks of disease may occur in vaccinated herds. Therefore, there is an urgent need for effective antiviral treatment. For three abortigenic (94P247, 97P70 and 99P96) and three neuropathogenic isolates (97P82, 99P136 and 03P37), the effect of acyclovir, ganciclovir, cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) and foscarnet on plaque number was studied. Additionally, for isolate 97P70, the effect on plaque size was investigated. Ganciclovir was most potent in reducing plaque number, followed by PMEDAP and acyclovir. Adefovir and cidofovir were less effective and foscarnet was the least effective compound. There were no differences detected for acyclovir, ganciclovir, adefovir and PMEDAP between the abortigenic and neuropathogenic isolates. One abortigenic isolate (99P96) was more susceptible to cidofovir and two neuropathogenic isolates (99P136 and 03P37) were less susceptible to foscarnet. For isolate 97P70, all compounds resulted in a significant reduction of plaque size. The most remarkable effect was observed for cidofovir. It was 40-fold more effective in reducing plaque size than in reducing plaque number. In conclusion, ganciclovir was the most potent compound and therefore, may be a valuable candidate for the treatment of EHV-1 infections in horses. The antiviral effect of foscarnet on plaque number was highly dependent on the viral isolate tested. Therefore, it is no valuable antiviral for the treatment of herpesvirus-infections. Cidofovir, although less effective in reducing plaque number, had a strong effect on plaque size. PMID- 17276632 TI - The Roach muscle bundle and umbilical cord coiling. AB - OBJECTIVE: To determine if presence of the Roach muscle, a small muscle bundle lying just beside the umbilical artery, contributes to umbilical cord coiling. METHODS: 251 umbilical cords were examined. The umbilical coiling index (UCI) was calculated as the number of coils divided by the cord length in cm. Cords were classified as hypocoiled (UCIp90). On microscopic examination of a cross section of the cord, absence or presence of a Roach muscle was determined. The t-test for independent samples and logistic regression were used for statistical analysis. RESULTS: A Roach muscle was observed in 101 cords. The mean UCI was higher in cords with the muscle bundle (0.23 coils/cm) than in cords without a muscle (0.18 coils/cm). Difference in mean: 0.05 coils/cm (95% C.I. 0.01-0.09). OR for hypercoiling in presence of the muscle was 2.98 (95% C.I. 1.57-5.64). OR for hypocoiling in the presence of the muscle was 1.49 (95% C.I. 0.79-2.81). CONCLUSIONS: Our results suggest that presence of a Roach muscle bundle contributes to umbilical cord coiling. Given the divergence in umbilical cord coiling within subgroups with or without this muscle, other factors must play a more dominant role. PMID- 17276633 TI - Use of avidin/biotin-liposome system for enhanced peritoneal drug delivery in an ovarian cancer model. AB - The goal of this study was to determine the distribution of the avidin/biotin liposome system in an ovarian cancer xenograft model. Optimal avidin/biotin liposome injection sequence with enhanced liposome accumulation to the peritoneum was determined. Two weeks after NIH:OVCAR-3 cell inoculation, rats were divided into three groups. Group 1 (B-A) (n=4), received an intraperitoneal injection of (99m)Tc-blue-biotin-liposomes 30 min before an intraperitoneal injection of avidin. Group 2 (A-B) (n=4), received an intraperitoneal injection of avidin 30 min before an intraperitoneal injection of (99m)Tc-blue-biotin-liposomes. Group 3 (A-B 2h) (n=5), received an intraperitoneal injection of avidin 2h before an intraperitoneal injection of (99m)Tc-blue-biotin-liposomes. Three additional non tumor nude rats served as controls in each group, and were subjected to the same injection sequences. Scintigraphic imaging commenced at various times post (99m)Tc-blue-biotin-liposome injection. After imaging, rats were euthanized at 23 h post-liposome injection for tissue biodistribution. Images showed no apparent difference in liposome distribution between control and tumor animals. Regional uptake analysis at 4h for tumor rats showed significantly higher lymphatic channel uptake in the A-B 2h group (p<0.05) and a trend of increased peritoneal uptake in A-B group. By 22 h, peritoneal and lymphatic channel uptake was similar for all groups. At necropsy, most activity was found in blue-stained omentum, diaphragm, mediastinal and abdominal nodes. Bowel activity was minimal. These results correlate with previous normal rat studies, and demonstrate potential use of this avidin/biotin-liposome system for prolonging drug delivery to the peritoneal cavity and associating lymph nodes in this ovarian cancer xenograft model. PMID- 17276634 TI - Woodfordia fruticosa: traditional uses and recent findings. AB - Woodfordia fruticosa Kurz of the family Lythraceae is a plant of tropical and subtropical region with a long history of medicinal use. A wide range of chemical compounds including tannins (especially those of macrocyclic hydrolysable class), flavonoids, anthraquinone glycosides, and polyphenols have been isolated from this species in recent times. Extracts and metabolites of this plant, particularly those from flowers and leaves, possess useful pharmacological activities. A comprehensive account of the chemical constituents and the biological activities is presented and a critical appraisal of the ethnopharmacological issues is included in view of the many recent findings of importance on this plant. PMID- 17276635 TI - Gastroprotective effect and cytotoxicity of terpenes from the Paraguayan crude drug "yagua rova" (Jatropha isabelli). AB - A new jatrophone derivative (6), jatrophone (3), jatropholone A (4) and jatropholone B (5), acetyl aleuritolic acid (1), cyperenoic acid (2) and a monoterpene were isolated from the rhizomes of the Paraguayan crude drug Jatropha isabelli. The compounds were characterized by spectroscopic means. The gastroprotective effect of jatrophone, jatropholone A and B as well as 9beta,13alpha-dihydroxyisabellione 6 and the triterpene 1 was assessed in the HCl/EtOH-induced gastric lesions model in mice. Jatrophone elicited a strong gastroprotective effect with no significant differences between 25, 50 or 100 mg/kg and reducing lesions from 88 to 93%. The jatropholones A and B showed remarkable differences in the gastroprotective assay. Jatropholone A presented a dose-related response, with maximum effect (54% lesion reduction) at the highest dose (100 mg/kg), jatropholone B showed a strong action at all the doses, reducing lesions by 83-91%. The cytotoxicity of the compounds was assessed towards fibroblasts and AGS cells. Jatrophone was toxic against both cell lines (IC50 values: 2.8 and 2.5 microM, respectively). Jatropholone B (5) was not cytotoxic while jatropholone A (4) displayed a selective effect against AGS cells (IC50: 49 microM). The relevance of stereochemistry in the biological effects is clear comparing the effect of jatropholone A and B against AGS cells, with IC50 values of 49 and > 1000 microM for the beta and alpha C-16 isomers, respectively. The results provide scientific support for the use of "yagua rova" as a gastroprotective crude drug in Paraguayan traditional medicine. PMID- 17276637 TI - Indian medicinal plants as a source of antimycobacterial agents. AB - It is estimated that one-third of the world's population is infected with tubercle bacillus and the problem of tuberculosis (TB) has been intensified due to HIV pandemic providing a large reservoir of highly susceptible individuals. Since no anti-TB drugs have been introduced in past 30 years, there is an urgent need to search for and develop new, effective and affordable anti-TB drugs. In this scenario, the plant kingdom with enormous chemical diversity may be looked as an important source of new anti-TB agents. Of 17,500 higher plant species occurring in India only about 365 species have been evaluated so far for antimycobacterial activity. The present review article describes the 255 (70% of 365) plant species from a wide range of families that have shown antimycobacterial activity. The species are enumerated in table format describing plant species and family, plant part used, type of extract and in vitro activity (MIC value), information on active compounds, if any, and uses in the ethnomedicine and Ayurveda. Interestingly, most of the plant species have shown strong positive ethnopharmacological correlation with the traditional knowledge. In addition, the recent in vitro screening methods for antimycobacterial activity are also described in brief. An attempt has been made to highlight the promising plant species for further investigation as leads for drug development. PMID- 17276636 TI - Protective effect of steamed American ginseng (Panax quinquefolius L.) on V79-4 cells induced by oxidative stress. AB - Heat-processed Asian ginseng roots (Panax ginseng C.A. Meyer), also known as "red ginseng" in Asia, are reported to have more bioactivity than the no-processed white ginseng roots. Therefore, American fresh ginseng roots (Panax quinquefolius L.) were processed to the red ginseng and examined changes in bioactivity during heating process. The fresh America ginseng roots were steamed at 100 degrees C for 30, 60, 90 and 120 min, and their bioactivities were examined by analyzing the content of ginsenosides and total phenolics, and measuring DPPH and superoxide radical scavenging acivity and their protective effects on V79-4 cells viability and lipid peroxidation. The heating treatment proportionally increased total ginsenosides (4.97%, w/w) content compared with white ginseng (3.27%) and total phenolics from 444.5 mg GAE/100 g to 489.6-574.2 mg GAE/100 g. The antioxidant activity also increased from 285 mg/100 g (vitamin C equivalent) to 353-487 mg/100 g. Heated ginseng showed high levels of DPPH radical scavenging activity (59.5-88.5%) and the high level of superoxide radical scavenging activity (44.2-90.9%). The heated ginseng protected cell viability against H2O2 induced oxidative damage, and enhanced the activities of superoxide dismutase and catalase by dose dependently in V79-4 cells. PMID- 17276638 TI - Parkinsonia aculeata aqueous extract fraction: biochemical studies in alloxan induced diabetic rats. AB - The antidiabetic effect of Parkinsonia aculeata water soluble fraction (WSF) made of aerial parts of the plant (leaves and flowers) was investigated in alloxan diabetic rats. Its effect was compared with that of insulin (positive control). The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum glucose, total cholesterol, HDL cholesterol, triglycerides, urinary glucose and urea, and the weight of epididymal adipose tissue, liver, kidneys and the skeletal muscles (soleus and extensor digitorum longus). Oral administration of WSF (125 or 250 mg/kg) for 16 days exhibited a significant reduction in serum and urinary glucose, urinary urea, total cholesterol, HDL-cholesterol and triglycerides in alloxan diabetic rats. An improvement of hepatic glycogen, a decrease of liquid and food intake, and a significantly positive actions in the weight of skeletal muscles (soleus and extensor digitorum longus) and kidneys were also observed, but just diabetic group treated with WSF at a dose of 125 mg/kg showed significant reduction in urinary volume, body weight, an improvement of epididymal adipose tissue and a positive action in liver weight. The effects of WSF on the physico-metabolic parameters was comparable to those observed in diabetic insulin treated group. The results of this work suggest that P. aculeate may have new clinical significant choice in diabetes mellitus illness, and could explain the basis for its traditional use to manage diabetes-related complications by rural community of northeast of Brazil. PMID- 17276639 TI - Fatal iatrogenic BaSO4 embolism: morphological and ultrastructural findings confirmed by X-ray microanalysis and ICP-AES. AB - A 42-year-old woman died from massive barium sulfate (BaSO(4)) lung embolism after a balloon catheter intended for elective colonography was inserted into her vagina. The vaginal insertion of the balloon catheter caused a bilateral laceration of the vaginal wall which was followed by penetration of BaSO(4) into the afferent veins and massive pulmonary embolism. Fluoroscopy performed during the fatal events and post-mortem X-rays revealed a radio-opaque substance in the vagina and uterus, the pelvic vessels and the vena cava, the right heart chambers, the lungs, and the kidneys. In addition to lungs, finely granular intravascular particles were demonstrated histologically in several organs including the brain and the glomerular capillaries. Scanning (SEM) and transmission (TEM) electron microscopy together with X-ray microanalysis, and inductively coupled plasma atomic emission spectrometry (ICP-AES) allowed the definite identification of BaSO(4) in lungs and confirmed its capacity to penetrate the pulmonary filter and to embolise via the systemic circulation in various organs. PMID- 17276640 TI - [Segmental occlusion of the internal carotid artery with collateral reinjection downstream from the carotid sinus]. AB - The preoperative evaluation before coronary bypass led to the discovery of complete atheromatous obstruction of the internal carotid artery sinus in a 79 year-old man free of any neurological symptom. Downstream from the carotid sinus, the patency of the internal carotid artery was ensured by a collateral branch fed by the ipsilateral external carotid artery. This exceptional anatomic variation can be explained by a persistent embryonic artery. The recognition of this atypical feature is clinically relevant because surgery may be possible in some cases, while it is not technically feasible in patients with total obstruction. PMID- 17276641 TI - [Ischemic stroke caused by Takayasu's arteritis]. AB - Takayasu's disease is a non specific, chronic, inflammatory panarteritis. It affects the aorta, its chief collaterals and the pulmonary arteries. Clinical manifestations depend on the site and the severity of the occlusive vascular lesion. We report a case observed in a young woman who presented ischemic stroke as the inaugural sign of Takayasu's disease. PMID- 17276642 TI - [Validation of an emergency care physician training program "two-point flash US"]. AB - BACKGROUND: The development of a short training program for emergency care physicians for rapid ultrasound assessment of two points (the groin and popliteal areas) could be useful for later implementation of a safe home care strategy for patients with suspected deep vein thrombosis before the results of a complete duplex-Doppler exploration are available. PURPOSE: Validation of the proposed training program by studying inter-operator agreement (trainee versus vascular physician) in a multicentric assessment of 60 emergency care physicians. Establish the learning curve. METHODOLOGY: Theoretical training: two-page document with schematic drawings and consultation of image bank on the Web. Practical training: 25 patients in all, the last 15 as an independent operator, writing a standardized report. Interoperator agreement: (a) centralized data collection and independent analysis of the report written by the trainee and a vascular physician for the same patients (n(o) 11 to 25); (b) determination of the coefficient of variance, kappa, and construction of the learning curve (900 agreement points for 60 trainees). INCLUSION CRITERIA: (a) Treated distal or proximal thrombosis recruited by the vascular physician (blinded to the result of the flash US); patient's oral consent. EXPECTED RESULTS: Learning curve leveling off at about the 20th patient with a kappa>0.61 or even 0.80. ORIGINAL CONTRIBUTION OF THE PROJECT: (a) Prospective, multicentric, blinded study: (i) confirming the feasibility of a two-point venous ultrasound performed by emergency care physicians; (ii) validation of the contents and duration of a short simplified training program; (b) Validation of a decision criterion for home care; If validated, this type of training program might be applied in other disciplines (intensive care, geriatrics). PMID- 17276643 TI - [Pathophysiology of pain in venous disease]. AB - Pain is the leading complaint of patients with venous disease. It has a significant effect on the patient's quality-of-life. For the clinician and the researcher however it is difficult to apprehend how pain is related to the venous disease, both because of the multiple factors involved and because of the lack of any strong relationship between pain symptoms and the severity of the venous disease. Currently, several hypotheses concerning the pathogenesis of pain in venous disease have focused on the causal impact of local inflammation. Over the last five years, a large body of evidence has been accumulation showing an inflammatory reaction around varicose veins, but the precise mechanism of how inflammatory mediators interact with venous nociceptors, which might explain part of the variability in pain observed in venous disease, remains elusive, both clinically and experimentally. PMID- 17276644 TI - [Prolonged postpneumococcal meningitis inflammatory syndrome]. PMID- 17276645 TI - The use of propofol sedation for transrectal ultrasonography-guided prostate biopsy is associated with high patient satisfaction and acceptability. PMID- 17276647 TI - [Critical reading of treatment trials]. AB - In view of the enormous quantity of medical information published, critical reading is essential for the rapid selection of information relevant to the physician's practice. Methodological quality is essential. The study design that produces the best evidence of the effects of an intervention is the randomized controlled clinical trial. Valid and reliable metaanalysis can increase the precision of these results. Only studies using clinically relevant outcome measures, analyzed according to intention to treat, deserve attention. Trials of lower methodological quality must be considered as hypothesis-generating trials. The groups receiving the study treatment and the reference treatment must be comparable to avoid sampling bias. The simpler the statistics, the more reliable the results, as a general rule. PMID- 17276646 TI - Macrophage biospecific extraction and high performance liquid chromatography for hypothesis of immunological active components in Cordyceps sinensis. AB - A method, namely macrophage biospecific extraction and high performance liquid chromatography for screening potential immunological active components in Cordyceps sinensis, a well-known traditional Chinese medicine, was developed. Two components, which could interact with macrophage, in aqueous extract of C. sinensis (WECS) were found by comparing the HPLC chromatograms of WECS before and after interacted with macrophage. The two compounds were identified as guanosine and adenosine. Their effects on mice macrophage were also investigated in vitro. The results showed that adenosine and guanosine could attenuate NO (p<0.01) but augment interleukin-lbeta (IL-1beta) (p<0.05) release of macrophage during the tested concentrations. In addition, guanosine (0.10 micromol/ml) also increased alpha-tumor necrosis factor (TNF-alpha) release of macrophage. The data suggest that macrophage biospecific extraction and HPLC is a useful method to screen immunological active components from Chinese medicines. PMID- 17276648 TI - [Validation of a questionnaire to screen for harmful use of alcohol and cannabis in the general population: CRAFFT-ADOSPA]. AB - BACKGROUND: Adolescents and young adults seeing a nurse or physician for any reason should be screened for psychoactive substance use. Several English language questionnaires are available to screen for and assess harmful use of psychoactive substances among adolescents, but to our knowledge, no such instrument exists in French. The aim of the ADOTECNO study was therefore to develop simple and efficient tools for this purpose. METHODS: Two questionnaires widely used in French epidemiologic studies (CRAFFT-ADOSPA to screen for harmful use and POSIT to assess the seriousness of consumption from physical, psychological and social viewpoints) were completed by 1728 secondary and post secondary school students. Statistical analyses assessed correlations between the questionnaires and calibrated optimal cutoff points for the different tools included in ADOTECNO. RESULTS: Correlations between psychoactive substance consumption, responses to the CRAFFT-ADOSPA questionnaire, and POSIT factor A scores showed that CRAFFT-ADOSPA provided early detection of regular alcohol intoxication and of regular and daily cannabis use. At a score of 2, CRAFFT ADOSPA detects harmful substance use, and at a score higher than or equal to 3 it demonstrates serious substance use. CONCLUSION: These findings enabled us to recommend useful cutoff values for the CRAFFT-ADOSPA tools for screening subjects at moderate or high risk of substance abuse. This simple broad screening should be complemented for the subjects found to be at risk by a computer-assisted POSIT to guide practitioners in selecting an approach (educational, school, family, psychological, psychiatric, etc.) to care and management according to the specific types of impairment resulting from substance use. PMID- 17276650 TI - [Dispersed cost control as a factor in hospital costs]. PMID- 17276649 TI - [Fabry disease: proposed guidelines from a French expert group for its diagnosis, treatment and follow-up]. AB - Fabry disease is a rare and under-recognized disease associated with an altered X linked gene controlling hydrolase alpha-galactosidase A activity. This mutation impairs the glycosphingolipid metabolism. A multisystemic disease with a highly variable clinical presentation, its principal symptom is acroparesthesia. Manifestations of Fabry disease occur mostly in hemizygous males but also in heterozygous females. Before enzyme replacement therapy was available, life expectancy was about 50 years in men and 70 years in women. Early diagnosis is essential to prevent irreversible organ damage. Diagnosis is based on an assay of alpha-galactosidase A activity in male patients and on genetic analysis in female patients. Prognosis is related principally to three complications: involvement of the central nervous system, kidneys, and heart. Management of Fabry patients should in all cases combine symptomatic therapy and regular clinical, laboratory and morphological follow-up by specialists in genetic metabolic diseases. Enzyme replacement therapy should be considered in all adult male patients and should probably begin early. In adult heterozygous female patients and in children, this treatment should be considered only for patients with severe pain, organ damage, or central nervous system, kidney, or heart involvement. After a proband is identified, a genealogical tree should be used to identify other affected members of the family. PMID- 17276651 TI - The VP1 structural protein of enterovirus 71 interacts with human ornithine decarboxylase and gene trap ankyrin repeat. AB - Enterovirus 71 (EV71) is a major etiological agent of hand, foot and mouth disease (HFMD). Several outbreaks in East Asia were associated with neurological complications and numerous deaths. EV71 possesses four structural proteins VP1 VP4 that are necessary in the formation of the pentameric icosahedral capsid. The viral capsid contributes to virulence, and VP1 is a prime target for EV71 vaccine development. Using yeast two-hybrid analysis, we demonstrated binding affinity between VP1 and three human proteins, i.e. ornithine decarboxylase (ODC1), gene trap ankyrin repeat (GTAR), and KIAA0697 expressed in brain tissue. These interactions were authenticated by co-immunoprecipitation experiments, and by indirect immunofluorescent confocal microscopy of transfected and EV71-infected Vero cells. The significant interaction between VP1 and ODC1 may compromise the latter's activity, and interfere with polyamine biosynthesis, growth and proliferation of EV71-infected cells. The interaction between VP1 and GTAR is noteworthy, since ankyrin proteins are associated with certain neural cell adhesion molecules and with the CRASH neurological syndrome. Given that VP1 is synthesized in large amounts during productive infection, these viral-host protein interactions may provide insights into the role of VP1 in the pathogenesis of EV71 disease and its neurological complications such as acute flaccid paralysis and encephalitis. PMID- 17276652 TI - The latent structure of cognitive symptom exaggeration on the Victoria Symptom Validity Test. AB - Previous studies have focused on the ability of cognitive symptom validity tests to identify simulated malingering or distinguish between clinical samples of individuals at low or high risk of cognitive symptom exaggeration. However, no published studies have examined the latent structure of negative response bias on cognitive tests: measures of cognitive symptom exaggeration may evaluate a continuum of poor effort/invalid responding or a dichotomy of adequate versus inadequate effort. The present study examined whether Victoria Symptom Validity Test (VSVT) indices evaluate a latent dimension or category of response distortion. The VSVT and personality data were obtained from 300 individuals who participated in neuropsychological evaluations as part of standard clinical care. Results indicated that VSVT accuracy scores measure a latent category of inadequate/adequate effort. Individuals classified as taxon members showed significantly poorer performance IQ and memory relative to individuals not classified as exhibiting distortion. The base rate of the identified cognitive symptom exaggeration taxon was estimated to be approximately .13-.14 in the present sample. Likelihood ratios are presented to assist clinical detection of individuals exhibiting the category of cognitive symptom exaggeration. PMID- 17276653 TI - Posttraumatic stress disorder symptoms following media exposure to tragic events: impact of 9/11 on children at risk for anxiety disorders. AB - With the extensive media coverage on September 11, 2001, adults and children indirectly witnessed the terrorist attacks leading to the deaths of almost 3,000 people. An ongoing longitudinal study provided the opportunity to examine pre event characteristics and the impact of this media exposure. We assessed symptoms of PTSD in 166 children and 84 mothers who had no direct exposure to the 9/11 attacks. The sample included children who had parents with or without anxiety and mood disorders, and who had been assessed for the presence or absence of temperamental behavioral inhibition (BI). We found a 5.4 percent rate of symptomatic PTSD in response to 9/11 in children and 1.2 percent in their mothers. Children's identification with victims of the attack, and for younger children, the amount of television viewing predicted increased risk of PTSD symptoms. Parental depression was associated with higher symptoms, and pre-event levels of family support was associated with a lower risk for PTSD symptoms. BI in children was also linked to lower rates of PTSD symptoms, suggesting that a cautious and fearful approach to novelty may offer protection against exposure to media-based traumatic images. Media viewing of tragic events is sufficient to produce PTSD symptoms in vulnerable populations such as children. Given the links between PTSD symptoms and viewing habits, parental monitoring of media exposure may be important for younger children. PMID- 17276654 TI - Applying genetic programming to the prediction of alternative mRNA splice variants. AB - Genetic programming (GP) can be used to classify a given gene sequence as either constitutively or alternatively spliced. We describe the principles of GP and apply it to a well-defined data set of alternatively spliced genes. A feature matrix of sequence properties, such as nucleotide composition or exon length, was passed to the GP system "Discipulus." To test its performance we concentrated on cassette exons (SCE) and retained introns (SIR). We analyzed 27,519 constitutively spliced and 9641 cassette exons including their neighboring introns; in addition we analyzed 33,316 constitutively spliced introns compared to 2712 retained introns. We find that the classifier yields highly accurate predictions on the SIR data with a sensitivity of 92.1% and a specificity of 79.2%. Prediction accuracies on the SCE data are lower, 47.3% (sensitivity) and 70.9% (specificity), indicating that alternative splicing of introns can be better captured by sequence properties than that of exons. PMID- 17276655 TI - A pair of new statistical parameters for quality control in RNA interference high throughput screening assays. AB - RNA interference (RNAi) high-throughput screening (HTS) enables massive parallel gene silencing and is increasingly being used to reveal novel connections between genes and disease-relevant phenotypes. The application of genome-scale RNAi relies on the development of high-quality RNAi HTS assays. To obtain high-quality HTS assays, there is a strong need for an easily interpretable and theoretically based quality control (QC) metric. Signal-to-noise ratio (S/N), signal-to background ratio (S/B), and Z-factor have been adopted as QC metrics in HTS assays. In this paper, I proposed a pair of new parameters, strictly standardized mean difference (SSMD) and coefficient of variability in difference (CVD), as QC metrics in RNAi HTS assays. Compared to S/B and S/N, SSMD and CVD capture the variabilities in both compared populations. Compared to Z-factor, SSMD and CVD have a clear probability interpretation and a solid statistical basis. Accordingly, the cutoff criteria of using SSMD or CVD as a QC metric in HTS assays are fully theoretically based. In addition, I discuss the relationship between the SSMD-based criterion and the popular Z-factor-based criterion and elucidate why p-value from t-test of testing mean difference fails to serve as a QC metric. PMID- 17276656 TI - Resolving the resolution of array CGH. AB - Many recent technologies have been designed to supplant conventional metaphase CGH technology with the goal of refining the description of segmental copy number status throughout the genome. However, the emergence of new technologies has led to confusion as to how to describe adequately the capabilities of each array platform. The design of a CGH array can incorporate a uniform or a highly variable element distribution. This can lead to bias in the reporting of average or median resolutions, making it difficult to provide a fair comparison of platforms. In this report, we propose a new definition of resolution for array CGH technology, termed "functional resolution," that incorporates the uniformity of element spacing on the array, as well as the sensitivity of each platform to single-copy alterations. Calculation of these metrics is automated through the development of a Java-based application, "ResCalc," which is applicable to any array CGH platform. PMID- 17276657 TI - Assessment of glucose metabolism from the projections using the wavelet technique in small animal pet imaging. AB - The dynamic positron emission tomography (PET) images are usually modeled to extract the physiological parameters. However, to avoid reconstruction of the dynamic sequence of images with subjective data filtering, it is advantageous to apply the kinetic modeling in the projection space and to reconstruct single parametric image slices. Using the advantage of the wavelets to compress the data and to filter the noise in the sinogram, we applied the graphical analysis method (Patlak) to generate a single parametric sinogram (WAV-SINO) from PET data acquired in seven normal rats measured with fluorodeoxyglucose (FDG) in the heart. The same data set was analysed with the graphical method in the spatial domain from the sinograms (USUAL-SINO), and also from images reconstructed with non-filtered backprojection (USUAL-nFBP) and filtered backprojection (USUAL-FBP). The myocardial metabolic rates for glucose (MMRG) obtained with USUAL-nFBP, USUAL FBP, USUAL-SINO and WAV-SINO were found to be, respectively, 7.54, 6.75, 6.52 and 6.98micromol/100g/min. While the variance with respect to USUAL-FBP was about 142% for USUAL-nFBP, 99.6% for USUAL-SINO and 101.9% for WAV-SINO, the spatial resolution as assessed from the profiles through the myocardial walls of the reconstructed images was 112% for USUAL-FBP and 105% for WAV-SINO relative to the high resolution USUAL-nFBP. The WAV-SINO parametric images showed slightly better visual quality than those obtained from the spatial domain. Finally, the wavelet filtering technique allowed to reduce the computing time, the storage space and particularly the variance in the MMRG parametric images while preserving the spatial resolution. PMID- 17276658 TI - Interpersonal trauma, war zone exposure, and posttraumatic stress disorder among veterans with schizophrenia. AB - The present study examined the prevalence of war zone exposure, interpersonal trauma and post-traumatic stress disorder (PTSD) in veterans with primary schizophrenia hospitalized on a VA inpatient psychiatric unit. Data were collected on a sample of male veterans (N=165) with a primary diagnosis of schizophrenia or schizoaffective disorder, who were consecutively admitted to a VAMC inpatient psychiatric unit. The prevalence of interpersonal trauma exposure and comorbid PTSD were assessed. Analyses also explored differences between those patients who had been identified with PTSD to those who screened positive but had not been previously identified as having PTSD. Ninety-six percent of the sample endorsed interpersonal trauma or exposure to a war zone. The prevalence of PTSD was 47% (n=78), although only 14% (n=11) of those who screened positive for PTSD had a diagnosis of PTSD in their medical record. Among those screening positive, having a chart diagnosis of PTSD was associated with more severe PTSD symptoms and combat exposure. Results suggest that PTSD is highly prevalent and under diagnosed among veterans with schizophrenia. Increased assessment of trauma and PTSD in this population is warranted. PMID- 17276659 TI - Modulation of innate and adaptive immunity by lactoferrin in human immunodeficiency virus (HIV)-infected, antiretroviral therapy-naive children. AB - Oral lactoferrin supplementation in human immunodeficiency virus (HIV)-infected, antiretroviral therapy-naive children resulted in a skewing of T-lymphocytes towards more differentiated subpopulations. Phagocytosis (P=0.01) and killing (P=0.009), Toll-like receptor 2 expression (P=0.01) and the interleukin 12/interleukin-10 ratio (P=0.001) were also improved by lactoferrin. Lactoferrin supplementation results in immune modulation and could be useful in HIV infection. PMID- 17276660 TI - Progressive changes of white matter integrity in schizophrenia revealed by diffusion tensor imaging. AB - Recent magnetic resonance imaging (MRI) studies using diffusion tensor imaging (DTI) have suggested reduced fractional anisotropy (FA) in the white matter (WM) of the brain in patients with schizophrenia. We tried to examine whether such reduction in FA exists and whether such changes in FA progress in an age dependent manner in a Japanese sample of chronic schizophrenia. FA values were compared between 42 patients with chronic schizophrenia and 42 controls matched for age and gender, by using DTI with voxel-by-voxel and region-of-interest analyses. Correlations of FA values with age and duration of illness were examined. Patients with schizophrenia showed lower FA values, compared to controls, in the widespread WM areas including the uncinate fasciculi and cingulum bundles. A significant group-by-age interaction was found for FA in the WM, i.e., age-related reduction of FA was more pronounced in schizophrenics than in controls. A significant negative correlation between FA and duration of illness was also found in the WM. Our data confirmed decreased FA in schizophrenics, compared to controls in the widespread WM areas. Such decreased FA values in schizophrenia might be attributable, at least in part, to progressive changes after the onset of the illness. PMID- 17276661 TI - [Screening for biliary atresia and stool colour: Method of colorimetric scale]. AB - Biliary atresia is a rare disease, but it is the major cause of neonatal cholestasis and the major indication for liver transplantation in children. Kasai procedure can restore bile flow and prevent or slow progression of disease in a proportion of patients. Data show that the earlier the Kasai procedure is performed, the better is the outcome. Therefore, rapid referral to an experienced centre, for prompt diagnosis and surgery, is strongly recommended. Unfortunately, the disease is often detected late, and Kasai procedure is performed after 60 days of age. In an attempt to achieve earlier diagnosis and better outcome of Kasai procedure, we propose to institute routine screening for biliary atresia using a stool colorimetric scale. This should help to identify earlier children who have acholic stools and may have biliary atresia. We postulate that this screening method will allow improving the results of the Kasai procedure and providing children with the best chance of survival with their native liver. PMID- 17276662 TI - [Diagnosing cow's milk allergy: a logical procedure]. PMID- 17276663 TI - Solid lipid nanodispersions containing mixed lipid core and a polar heterolipid: characterization. AB - This paper describes the characterization of solid lipid nanodispersions (SLN) prepared with a 1:1 mixture of theobroma oil and goat fat as the main lipid matrix and Phospholipon 90G (P90G) as a stabilizer heterolipid, using polysorbate 80 as the mobile surfactant, with a view to applying the SLN in drug delivery. The 1:1 lipid mixture and P90G constituting the lipid matrix was first homogeneously prepared by fusion. Thereafter, the SLN were formulated with a gradient of polysorbate 80 and constant lipid matrix concentration by melt-high pressure homogenisation. The SLN were characterized by time-resolved particle size analysis, zeta potential and osmotic pressure measurements, differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). Transmission electron microscopy (TEM) and isothermal heat conduction microcalorimetry (IMC) which monitors the in situ crystallization were also carried out on the SLN containing P90G and 1.0 % w/w of polysorbate 80. The results obtained in these studies were compared with SLN prepared with theobroma oil with and without phospholipid. Particle size analysis of SLN indicated reduction in size with increase in concentration of mobile surfactant and was in the lower nanometer range after 3 months except SLN prepared without P90G or polysorbate 80. The lipid nanoparticles had negative potentials after 3 months. WAXD and DSC studies revealed low crystalline SLN after 3 months of storage except in WAXD of SLN formulated with 1.0 % w/w polysorbate 80. TEM micrograph of the SLN containing 1.0 % w/w polysorbate 80 revealed discrete particles whose sizes were in consonance with the static light scattering measurement. In situ crystallization studies in IMC revealed delayed crystallization of the SLN with 1.0 % w/w polysorbate 80. Results indicate lipid mixtures produced SLN with lower crystallinity and higher particle sizes compared with SLN prepared with theobroma oil alone with or without P90G, and would lead to higher drug incorporation efficiency when used in formulation of actives. Mixtures of theobroma oil and goat fat would be suitable for the preparation of nanostructured lipid carriers. SLN of theobroma oil containing phospholipid could prove to be a good ocular or parenteral drug delivery system considering the low particle size, particle size stability and in vivo tolerability of the component lipids. SLN prepared with lipid admixture, which had higher increase in d(90%) on storage are suitable for preparation of topical and transdermal products. PMID- 17276664 TI - Alginate-based pellets prepared by extrusion/spheronization: a preliminary study on the effect of additive in granulating liquid. AB - The aim of this study was to investigate the possibility of producing alginate based pellets by extrusion/spheronization and also to improve the formation of spherical alginate-based pellets by investigating the effect of additive in granulating liquid on characteristics and drug release from resulting pellets. Two types of sodium alginate (30%) were evaluated in combination with theophylline (20%), microcrystalline cellulose (50%) and different granulation liquids. The pellets were then prepared in a basket extruder, then spheronized and dried. The final products were characterized by morphological examination and drug release study. Different additives in the granulating liquid influenced the ability of the extruded mass to form pellets (the processability) with this technique. However, different sodium alginate types responded to shape modifications to a different extent. Long, dumbbell-shaped pellets were obtained with viscous granulating liquids. However, short, nearly spherical pellets were obtained with watery granulation liquid with calcium chloride that reduced the swelling ability of sodium alginate. Improvements in the pellet characteristics were also dependent on the sodium alginate type employed. Most of pellet formulations released about 75-85% drug within 60min and showed a good fit into both Higuchi and Korsmeyer-Peppas equations. Higher amount of 3% calcium chloride, as a granulating liquid, in the formulation showed higher mean dissolution time resulting from the cross-linking properties of calcium ions to the negative charges of alginate molecules. PMID- 17276665 TI - Mechanical characterization of pharmaceutical solids: a comparison between rheological tests performed under static and dynamic porosity conditions. AB - The aim of this work was to verify how and to what extent rheological tests, carried out under dynamic (Heckel) and static (creep, stress/strain) porosity conditions, may serve as a valuable complement to the classic Heckel tests in the characterization of viscoelastic and densification properties of solid materials for pharmaceutical use. Six different modified (pregelatinized) starches were compressed in a rotary tablet machine equipped to measure force and punch displacement. Tablets were obtained using flat-faced 6mm diameter punches at different compression pressures. Compression cycles performed at the maximal pressure of 200MPa were used to build the Heckel plots. Ejected tablets at the 10%, 20%, 30%, and 40% porosity levels were used for the stress/strain and creep tests. Parameters obtained with both types of tests were consistent with each other. In particular, among the six starches, lower viscosity values corresponded to lower P(Y) values, and lower elastic modulus values corresponded to lower elastic recovery of the tablet. Mechanical properties of materials can be better characterized if viscoelastic tests performed under dynamic porosity conditions (Heckel analysis) are supported by classical viscoelastic tests carried out under conditions of static porosity. PMID- 17276666 TI - Studies on acidification in two-phase biomethanation process of municipal solid waste. AB - Biomethanation of municipal solid waste (MSW) is a slow process and the yield of biogas is usually low. Enhancement of acidification is necessary to increase the biogas yield in biomethanation of MSW. MSW contains a significant fraction of ligno-cellulosic material. The acidification of these materials influences the biogas yield. In the present study, hydrolysis and acidification have been considered as a combined phase. Experiments have been conducted to study the effect of recirculation of leachate on the acidification stage of the two-phase biomethanation process. Chemical oxygen demand (COD) and volatile fatty acid (VFA) were considered as indicator parameters. The study was also conducted to investigate the effect of using acid and alkali solution of 0.1% concentration in the acidification study. It was observed that daily recirculation of leachate does not have any major impact on the acidification process. It was also observed that treatment of MSW with sodium hydroxide yields leachate of significantly higher COD and VFA values compared to others. PMID- 17276667 TI - Exercise-induced anaphylaxis and pregnancy. PMID- 17276669 TI - Influence of uterine exteriorization versus in situ repair on post-Cesarean maternal pain: a randomized trial. AB - BACKGROUND: This study was done to compare post-cesarean delivery pain associated with routine exteriorization of the uterus versus in situ uterine repair in the puerperium. METHODS: This prospective study included 206 women who underwent cesarean delivery under general anesthesia and who were randomly assigned to two groups based on the site of uterine repair: exteriorized uterine repair (102 women) versus in situ uterine repair (104 women). Exclusion criteria were neuraxial blockade and patient refusal to participate. Visceral and incisional pain was assessed on the first and second postoperative nights using a visual analog score of 0-100 mm. RESULTS: There were no significant differences between the groups in maternal age, weight, gestational age, race, preoperative hemoglobin or gravidity. All subjects underwent general anesthesia and had a low transverse incision of the uterus. Exteriorization was associated with higher postoperative visceral pain scores: first night 66.7 vs. 43.5 (P<0.001); second night 44.6 vs. 23.9 (P<0.001). The incidence of postoperative fever and wound infection, postoperative hemoglobin and duration of hospital stay were similar between groups. CONCLUSION: Exteriorization of the uterus for repair of the uterine incision increases the first- and second-night postoperative pain significantly in women undergoing cesarean section. PMID- 17276670 TI - Local infiltration of epinephrine-containing lidocaine with bicarbonate reduces superficial bleeding and pain during labor epidural catheter insertion: a randomized trial. AB - BACKGROUND: Superficial bleeding after labor epidural catheter placement is a common phenomenon. In addition to delaying securing the epidural catheter, it may loosen the adhesive catheter dressing. The primary aim of this study was to determine whether skin infiltration with epinephrine-containing rather than plain lidocaine reduces superficial bleeding after catheter placement. Secondary objectives were to determine whether adding epinephrine and/or sodium bicarbonate affected infiltration pain. METHODS: After institutional review board approval and informed consent, 80 healthy women receiving epidural analgesia during labor were randomly assigned in a double-blind manner to four local anesthetic mixtures (n=20 in each group): group L: lidocaine 1.5%, group LB: lidocaine 1.5% with 8.4% sodium bicarbonate, group LE: lidocaine 1.5% with epinephrine 1:200000, and group LEB: lidocaine 1.5% with epinephrine 1:200000 and 8.4% sodium bicarbonate. Clinical endpoints included the amount of superficial bleeding at the catheter site, pain during local anesthetic infiltration and epidural catheter movement during labor. RESULTS: Demographic data were similar among the groups. The addition of epinephrine to lidocaine significantly reduced superficial bleeding. Solutions containing epinephrine were well tolerated and caused no cardiovascular disturbances. The addition of epinephrine did not increase pain, while bicarbonate reduced it [verbal score (scale 0-10) 3.6+/-2.2 vs. 2.6+/-1.8; P=0.04]. There were no differences in epidural catheter movement among the groups; no catheters became displaced during labor. CONCLUSION: Local infiltration of epinephrine-containing lidocaine before epidural catheter insertion reduces superficial bleeding and the addition of bicarbonate decreases pain during skin infiltration. PMID- 17276668 TI - Prediction of hypotension during spinal anesthesia for Cesarean section and its relation to the effect of crystalloid or colloid preload. AB - BACKGROUND: If parturients prone to develop caval compression in the supine position were identified before delivery, this might be a method of predicting hypotension during caesarean section under spinal anesthesia. Colloid preloading is superior to crystalloid in reducing the risk for spinal anesthetic-induced hypotension. It is postulated that parturients preoperatively susceptible to the supine position would benefit the most from colloid preloading. METHODS: Fifty five healthy parturients scheduled for elective cesarean section under spinal anesthesia were preoperatively investigated with a supine stress test with measurement of maternal heart rate, blood pressure, right uterine artery pulsatility index and symptoms in the left lateral and supine positions. They were then randomized to receive a colloid or crystalloid preload before anesthesia. RESULTS: The stress test was positive, indicating a reduced tolerance to the supine position, in 36%. The sensitivity and specificity of the stress test for clinically significant hypotension (symptomatic hypotension) for patients randomized to the crystalloid group (n=25) were 69 and 92% respectively. Patients with a positive stress test receiving a crystalloid preload showed a higher frequency of hypotension compared to all other groups, 90% vs. 33%, (P=0.003) and also a greater need for ephedrine, mean dose (SD): 20.0 (9.7) vs. 8.4 (9.0) mg (P=0.002). CONCLUSIONS: Pregnant women with a positive preoperative supine stress test constitute a subset at increased risk for clinically significant hypotension during cesarean delivery under spinal anesthesia. These women seem more likely to benefit from prophylactic colloid solution than women with a negative stress test. PMID- 17276671 TI - Clinical value of combined determination of plasma L-DOPA/tyrosine ratio, S100B, MIA and LDH in melanoma. AB - AIM OF THE STUDY: L-DOPA/tyrosine ratio (an index of tyrosinase activity), melanoma antigens S100B and MIA, lactate deshydrogenase (LDH) and their combinations were evaluated for clinical value as tumour markers in melanoma. METHODS: Blood samples were obtained in 170 melanoma patients (stage I-II: n=57, III: n=54, IV: n=59) at inclusion and in a sub-group of 82 subjects during follow up for up to 4 years. Laboratory analyses were performed by HPLC (L-DOPA, L tyrosine), immunoassays (S100B, MIA) and colourimetry (LDH). RESULTS: All markers, except LDH, were elevated in stage IV versus other stages. S100B and MIA highly correlated, especially in stage IV (r(s): 0.849, p<0.001). The combination of L-DOPA/tyrosine ratio with S100B displayed the highest sensitivity/specificity (73/70%) to confirm stage III-IV or stage IV alone (69/75%) (ROC optimised cut off). Only the L-DOPA/tyrosine ratio significantly increased (+36% over 5 months, p=0.001) during progression from stage I-III to higher stages. S100B, MIA and LDH, but not the L-DOPA/tyrosine ratio, responded to progression towards death in stage IV. All markers exhibited a prognostic value in deceased patients (n=44); S100B and MIA were the best predictors of survival time by Cox proportional hazards regression. CONCLUSION: The combination of plasma L-DOPA/tyrosine ratio and S100B appears an attractive approach for the biological follow-up of melanoma patients. PMID- 17276672 TI - Guidelines on the standards for the training of specialised health professionals dealing with breast cancer. AB - According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care. PMID- 17276673 TI - Overexpression of LAPTM4B-35 closely correlated with clinicopathological features and post-resectional survival of gallbladder carcinoma. AB - Gallbladder carcinoma (GBC) is a malignancy with dismal prognosis and unclear gene expression profile. We aimed to first present the expression of LAPTM4B-35, one product of a cancer associated gene recently cloned in hepatocellular carcinoma (HCC), and its correlation with clinicopathological features and prognosis of GBC. Immunohistochemical detection of LAPTM4B-35 was performed on samples from 75 patients with GBC. LAPTM4B-35 protein was overexpressed in 57 patients (76%) with GBC. The staining scores were significantly related to histology type, lymph node involvement, distant metastasis, Nevin staging and differentiation of GBC (P<0.05). Univariate analysis revealed that overall or disease-free survival of patients was inversely associated with its staining scores (P<0.001). Multivariate analysis showed that LAPTM4B-35 staining score was an independent prognostic marker for both overall and disease-free post resectional survival of GBC (P=0.004 and 0.027, respectively). LAPTM4B-35 overexpressed in a majority of GBCs and correlated with clinicopathological features and post-resectional survival. PMID- 17276674 TI - A review of composting as a management alternative for beef cattle feedlot manure in southern Alberta, Canada. AB - Composting is gaining increased acceptance as a management alternative for the large volumes of manure produced by southern Alberta's beef cattle feedlots. Research on windrow composting of feedlot manure was initiated at the Lethbridge Research Centre of Agriculture and Agri-Food Canada in 1996. Early studies looked at physical and chemical changes during composting. Studies have also been conducted on greenhouse gas emissions during composting and the effect of composting on reduction of pathogens, parasites and weed seed viability. The quality of commercially-produced composts at southern Alberta feedlots has been examined as has the mineralization rates of soil-applied composts. This paper reviews results from our feedlot manure composting research program. PMID- 17276675 TI - Feasibility study of the anaerobic digestion of dewatered pig slurry by means of polyacrylamide. AB - Liquid livestock waste can be managed by separating liquid and solid fractions then treating each separately by applying best available technology, such as anaerobic digestion for the solid fraction. There is an increasing use of polyacrylamide (PAM) as a flocculant agent to improve solid-liquid separation. In the present work, the anaerobic toxicity of PAM residues and the optimal range of total solids concentration for maximum methane production were studied as a function of PAM dosage. Results showed that dry matter and its volatile solids content increased significantly with increasing PAM dosage. Batch anaerobic tests showed that methane yield decreased linearly with increasing total solids, while the methane production per unit of raw substrate reached a maximum at 16.4% total solids. No PAM toxicity was measured for PAM concentrations below 415 g/kg total solids, but some indirect inhibitory phenomena were observed, such as a limited hydrolysis rate due to particle aggregation, and inhibition of methanogenesis by high ammonia concentration. PMID- 17276677 TI - Self-aggregation of zinc chlorophylls possessing perfluoroalkyl chains in fluorous solvents: Selective extraction of the self-aggregates with fluorous phase and accelerated formation of the ordered supramolecules in this phase. AB - Zinc 3(1)-hydroxy-13(1)-oxo-chlorins possessing various perfluorooctyl groups in the 17-propionate were prepared by modifying naturally occurring chlorophyll-a. The synthetic compound having four perfluorooctyl groups readily self-assembled to form large J-aggregates, which were dissolved in fluorous phases with more ordered supramolecular structures than in a hydrocarbon solvent. PMID- 17276676 TI - A new 4-(2-methylquinolin-4-ylmethyl)phenyl P1' group for the beta-amino hydroxamic acid derived TACE inhibitors. AB - A new P1' group for TACE inhibitors was identified by eliminating the oxygen atom in the linker of the original 4-(2-methylquinolin-4-ylmethoxy)phenyl P1' group. Incorporation of this 4-(2-methylquinolin-4-ylmethyl)phenyl group onto different beta-aminohydroxamic acid cores provided compound 18, which demonstrated potent porcine TACE (p-TACE) and human whole blood activity, excellent PK properties, and good selectivity against a variety of MMPs. PMID- 17276678 TI - Degradation of DNA by bisulfite treatment. AB - A significant level of target degradation was caused by bisulfite treatment for methylcytosine-selective hydrolysis. The depyrimidination proceeded via addition of bisulfite to pyrimidines in DNA. The quantification with real-time PCR after conventional bisulfite treatment showed a large decrease in the amount of full length DNA. PMID- 17276679 TI - A non-toxic Hsp90 inhibitor protects neurons from Abeta-induced toxicity. AB - The molecular chaperones have been implicated in numerous neurodegenerative disorders in which the defining pathology is misfolded proteins and the accumulation of protein aggregates. In Alzheimer's disease, hyperphosphorylation of tau protein results in its dissociation from microtubules and the formation of pathogenic aggregates. An inverse relationship was demonstrated between Hsp90/Hsp70 levels and aggregated tau, suggesting that Hsp90 inhibitors that upregulate these chaperones could provide neuroprotection. We recently identified a small molecule novobiocin analogue, A4 that induces Hsp90 overexpression at low nanomolar concentrations and sought to test its neuroprotective properties. A4 protected neurons against Abeta-induced toxicity at low nanomolar concentrations that paralleled its ability to upregulate Hsp70 expression. A4 exhibited no cytotoxicity in neuronal cells at the highest concentration tested, 10 microM, thus providing a large therapeutic window for neuroprotection. In addition, A4 was transported across BMECs in vitro, suggesting the compound may permeate the blood-brain barrier in vivo. Taken together, these data establish A4, a C terminal inhibitor of Hsp90, as a potent lead for the development of a novel class of compounds to treat Alzheimer's disease. PMID- 17276680 TI - Quinuclidines as selective agonists for alpha-7 nicotinic acetylcholine receptors. AB - The alpha7 subtype of the neuronal nicotinic acetylcholine receptors (nAChRs) was targeted for the design of selective agonists deriving from the quinuclidine scaffold. Arylidene groups at the 3-position and N-methyl quinuclidine were found to be selective agonists with EC(50)s of 1.5 and 40 microM, respectively. PMID- 17276681 TI - Discovery of novel 2,3-diarylfuro[2,3-b]pyridin-4-amines as potent and selective inhibitors of Lck: synthesis, SAR, and pharmacokinetic properties. AB - 2,3-Diarylfuro[2,3-b]pyridine-4-amines are a novel class of potent and selective inhibitors of Lck. The discovery, synthesis, and structure activity relationships of this series of inhibitors are reported. The most promising compounds were also profiled to deduce their pharmacokinetic properties. PMID- 17276682 TI - Synthesis, antimycobacterial activity evaluation, and QSAR studies of chalcone derivatives. AB - In order to develop relatively small molecules as antimycobacterial agents, twenty-five chalcones were synthesized, their activity was evaluated, and quantitative structure-activity relationship (QSAR) was developed. The synthesis was based on the Claisen-Schimdt scheme and the resultant compounds were tested for antitubercular activity by luciferase reporter phage (LRP) assay. Compound C(24) was found to be the most active ( approximately 99%) in this series based on the percentage reduction in Relative Light Units at both 50 and 100 microg/ml levels, followed by compound C(21). Four compounds at the 50 microg/ml and eight compounds at the 100 microg/ml showed activity above 90% level. QSAR model was developed between activity and spatial, topological, and ADME descriptors for the 50 microg/ml data. The statistical measures such as r, r(2), q(2), and F values obtained for the training set were in acceptable range and hence this relationship was used for the test set. The predictive ability of the model is satisfactory (q(2)=0.56) and it can be used for designing similar group of compounds. PMID- 17276683 TI - N-Hydroxythiosemicarbazones: synthesis and in vitro antitubercular activity. AB - N-Hydroxythiosemicarbazide was prepared by two methods starting from 2,4 dimethoxy benzyl amine and hydroxylamine hydrochloride, which in turn was reacted with various aldehydes and ketones to obtain the titled compounds. Eighteen compounds were tested for their in vitro activity against Mycobacterium tuberculosis H37Rv using the agar dilution method. Compound 10p was found to be the most potent compound (MIC: 0.28 microM) and was 2.5 times more active than standard isoniazid. PMID- 17276684 TI - From pyrroles to 1-oxo-2,3,4,9-tetrahydro-1H-beta-carbolines: a new class of orally bioavailable mGluR1 antagonists. AB - Exploiting the SAR of the known pyrrole derivatives, a new class of mGluR1 antagonists was designed by replacement of the pyrrole core with an indole scaffold and consequent cyclization of the C-2 position into a tricyclic beta carboline template. The appropriate exploration of the position C-6 with a combination of H-bond acceptor groups coupled with bulky/lipophilic moieties led to the discovery of a new series of mGluR1 antagonists. These compounds exhibited a non-competitive behavior, excellent pharmacokinetic properties, and good in vivo activity in animal models of acute and chronic pain, after oral administration. PMID- 17276685 TI - High-affinity carbamate analogues of morphinan at opioid receptors. AB - A series of carbamate analogues were synthesized from levorphanol (1a), cyclorphan (2a) or butorphan (3a) and evaluated in vitro for their binding affinity at mu, delta, and kappa opioid receptors. Functional activities of these compounds were measured in the [(35)S]GTPgammaS binding assay. Phenyl carbamate derivatives 2d and 3d showed the highest binding affinity for kappa receptor (K(i)=0.046 and 0.051 nM) and for mu receptor (K(i)=0.11 and 0.12 nM). Compound 1c showed the highest mu selectivity. The preliminary assay for agonist and antagonist properties of these ligands in stimulating [(35)S]GTPgammaS binding mediated by the kappa opioid receptor illustrated that all of these ligands were kappa agonists. At the mu receptor, compounds 1b, 1c, 2b, and 3b were agonists, while compounds 2c-e and 3c-e were mu agonists/antagonists. PMID- 17276686 TI - Synthesis and biological evaluation of two glycerolipidic prodrugs of didanosine for direct lymphatic delivery against HIV. AB - Novel glycerolipidic prodrugs of didanosine and didanosine monophosphate designed to by-pass the hepatic first pass metabolism were synthesized and tested for their cytotoxicity and anti-HIV-1 activity. Formulation as liposomes of dipalmitoylphosphatidylcholine was elaborated. A simple quantitative HPLC-UV method was developed and validated, and ESI-MS was used for qualitative purpose. These two prodrugs exhibited promising biological activities against HIV-1 in in vitro infected cell culture. PMID- 17276687 TI - Structure-based design of benzylamino-acridine compounds as G-quadruplex DNA telomere targeting agents. AB - The design, synthesis, biophysical and biochemical evaluation is presented of a new series of benzylamino-substituted acridines as G-quadruplex binding telomerase inhibitors. Replacement of the previously reported anilino substituents by benzylamino groups results in enhanced quadruplex interaction, and for one compound, superior telomerase inhibitory activity. PMID- 17276688 TI - Long distance running increases plantar pressures beneath the metatarsal heads: a barefoot walking investigation of 200 marathon runners. AB - BACKGROUND: The growing popularity of endurance sports activities is associated with a growing number of metatarsal stress fractures in recreational runners. Excessive foot loading has been suggested as a potential cause for these problems [Bennell, K, Matheson G, Meeuwisse W, Brukner P. Risk factors for stress fractures. Sports Med 1999;28(2):91-122]. Therefore, the question arises whether long distance running affects foot loading characteristics like ground reaction forces and peak pressure in specific areas of the foot. PURPOSE: To investigate the effects of long distance running on plantar pressure patterns before and after a marathon race. STUDY DESIGN: Repeated measurements of recreational runners before and after a marathon race. METHODS: Two hundred participants of the third Muenster marathon, 2004, were measured before and after the race with plantar pressure measurements during barefoot walking on a capacitive platform. The ratio between forefoot and toe loading was calculated to assess a suggested loading shift between these areas. RESULTS: The results of the whole group of participants revealed a significant difference in foot loading characteristics before and after the race. Post-race peak pressure and impulse values were higher in the forefoot regions and reduced under the toes. CONCLUSIONS: The increased peak pressure under the metatarsal heads after the race indicates a load shift from the toes to the metatarsal heads. This suggests an increased loading of the metatarsal bones and could explain the increased incidence of metatarsal stress fractures in long distance runners. PMID- 17276689 TI - Multiple brain metastases from malignant thymoma. AB - A rare case of thymic carcinoma with multiple brain metastasis is reported. In our extensive review of the literature only six of 30 reports of intracranial thymoma metastasis describe multiple metastases. A 38-year-old man presented with signs of raised intracranial pressure that had began 15 days previously. Cranial MRI revealed over 70 cystic lesions in the supra and infratentorial regions. Stereotactic biopsy was planned. On the second day of his admission he deteriorated and died the following day. The autopsy revealed a mass in the mediastinum. In the brain parenchyma were multiple cystic lesions between 0.5 and 3 cm in diameter. Histopathologically they were diagnosed as metastases from the thymic carcinoma. The mean survival with a single brain metastasis is approximately 256 days, whereas with multiple brain metastases it is only 64 days, thus treatment of this tumor demands prompt surgery whenever possible and optimal adjuvant therapy. PMID- 17276691 TI - Histology and ultrastructure of pericardial cells of Scaptotrigona postica Latreille (Hymenoptera, Apidae) in workers and queens of different ages. AB - The paper presents a study of the pericardial cells of Scaptotrigona postica an eusocial Brazilian stingless bee. Light and electron microscopy was used in a comparative study on workers and queens of different ages, exerting different functions in the colony. The pericardial cells are found only in the pericardial sinus, mainly in groups around the dorsal vessel. Each cell is enclosed by the basal membrane and its peripheral region is characterized by folds of the plasma membrane, which form canals and loops. The points where the plasma membrane folds is frequently closed by diaphragms, that along with the basal lamina form a barrier to substances from hemolymph. Along the membrane limiting the canals and loops, an intense endocytic activity through coated vesicles takes place indicating a selective absorption of hemolymph components. In older individuals, workers or queens, the cells exhibit larger quantities of cytoplasm inclusions, heterogeneous vacuoles containing the final products of intracellular digestion, and autophagic vacuoles with concentric membranous structures. The pericardial cells general morphology is in accordance with the role in processing metabolites captured from hemolymph and storage of indigested residues. PMID- 17276690 TI - Naphthoindole-based analogues of tryptophan and tryptamine: synthesis and cytotoxic properties. AB - The efficacy of anthracycline based anticancer drugs is limited by pleiotropic drug resistance of tumor cells. Aiming at the design of anthracyclinone congeners capable of circumventing drug resistance, we synthesized naphthoindole containing derivatives of tryptophan and tryptamine. In doing so we adapted the traditional, gramine based approach for tryptophan and tryptamine synthesis. The most potent new compound, 3-(2-aminoethyl)-4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione (16), was equally cytotoxic (IC(50) within low micromolar concentrations) for human K562 leukemia and HCT116 colon carcinoma cell lines and their isogenic sublines with genetically defined determinants of altered drug response, that is, the expression of the multidrug transporter P-glycoprotein and loss of pro apoptotic p53. Each of these mechanisms conferred resistance to the reference drug adriamycin. In contrast, naphthotryptamine 16, although less potent than adriamycin, was equally toxic for wild type cell lines and drug resistant counterparts. Moreover, at 3-5 microM 16 inhibited topoisomerase I in vitro. Thus, our novel naphthoindole based derivative of tryptamine gained new activities important for anticancer therapy, namely, suppression of topoisomerase I and the ability to overcome resistance mediated by P-glycoprotein expression and p53 dysfunction. PMID- 17276692 TI - Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain. AB - The YAC128 mouse model of Huntington disease (HD) exhibits motor abnormalities, cognitive dysfunction and selective neuropathology which are similar to the human disease. Backcrossing YAC128 mice from the FVB/N strain onto the C57BL/6 strain and the 129 strain revealed that striatal volume loss and motor dysfunction are penetrant on all three genetic backgrounds. The severity of HD-like phenotypes in these mice is modulated by strain and this variation is not accounted for by differences in mutant huntingtin expression. In contrast, nuclear localization of mutant htt is modulated by strain and is correlated with the severity of neuropathology. Differences in phenotypic severity between the strains provide the opportunity to identify modifier genes which could impact the pathogenesis of HD. Importantly, the demonstration of penetrance across all three strains permits examining the effect of specific genes on the phenotypic severity in YAC128 mice without necessarily backcrossing onto the FVB/N strain background. PMID- 17276693 TI - Subclavian flap aortoplasty: still a safe, reproducible, and effective treatment for infant coarctation. AB - OBJECTIVE: Subclavian flap repair of infant coarctation has been criticized and in many centers abandoned in favor of resection with end-to-end anastomosis. The goal of this study was to examine intermediate and long-term results of infant subclavian flap aortoplasty, which has been the preferred technique at our institution over the last two decades. METHODS: Our patient database identified all infants (age<1 year) who underwent repair of isthmic coarctation via thoracotomy between January 1984 and December 2004. Procedure details and late results were collected by retrospective review of hospital and clinic data. Follow-up was 95.8% complete at a mean of 6.7 years. RESULTS: Between January 1984 and December 2004, 119 infants underwent isolated subclavian flap repair of coarctation. Mean age and weight at operation were 35+/-52 days (range 1-269 days) and 3.5+/-1.3kg (range 0.7-9.3kg), respectively. Concomitant pulmonary artery banding was performed in 22% (26/119). In-hospital mortality was 4% (5/119) and cumulative late mortality was 6% (7/114) of patients with long-term follow-up. Actuarial survival at 1, 5, and 10 years was 91, 85, and 85%, respectively. Overall re-intervention rate for re-stenosis was 11% (12/114); 10 patients (9%) underwent balloon angioplasty while 3 patients (3%) required operative revision. All re-stenoses occurred in the descending aorta, and all occurred in patients who had undergone neonatal repair. At late follow-up, there were no significant neurologic events (left recurrent laryngeal nerve injury, stellate ganglion dysfunction, or paraplegia), no clinically significant ischemic arm complications, and no flap aneurysms. CONCLUSIONS: Subclavian flap aortoplasty remains our procedure of choice for isthmic coarctation, as it is a simple, technically straightforward technique with a low incidence of re-stenosis and serious early and late morbidity. Furthermore, subclavian flap re-stenoses are easily treated with percutaneous intervention and seldom require surgical re intervention via thoracotomy. PMID- 17276694 TI - Sexual versus individual differentiation: the controversial role of avian maternal hormones. AB - Avian embryos are exposed not only to endogenous sex steroids, which are produced by their gonads and have a key role in sexual differentiation, but also to maternal steroids transferred into the egg yolk, which can modulate the development of individual differences in behavior. Studies of maternal hormones have primarily focused on ultimate questions (evolutionary trade-offs, functional significance), whereas proximate mechanistic questions have been largely ignored. A central problem that must be addressed is how exposure to maternal hormones affects the individual phenotype without interfering with sexual differentiation. Separate effects could result from the action of different hormones, at different doses or at different times, on different targets. PMID- 17276695 TI - Innate control of adaptive immunity: dendritic cells and beyond. AB - Innate immune recognition of pathogens triggers both immediate defenses against the invading pathogens and the initiation of adaptive immune responses. Dendritic cells (DCs) play a key role in sensing and processing microbial information and directing the differentiation of naive lymphocytes to effector cells suitable against particular types of infections. These processes within DCs are intricately controlled at the levels of the cell, anatomical location, migration and their interaction with other cell types. This review focuses on recent understanding of the contributions of several key cell types, which regulate, and are regulated by DCs, in the generation of adaptive immune responses. PMID- 17276697 TI - Some issues raised by the current influenza H5N1 outbreak. PMID- 17276696 TI - Novel regional and developmental NMDA receptor expression patterns uncovered in NR2C subunit-beta-galactosidase knock-in mice. AB - NMDA receptor "knock-in" mice were generated by inserting the nuclear beta galactosidase reporter at the NR2C subunit translation initiation site. Novel cell types and dynamic patterns of NR2C expression were identified using these mice, which were unnoticed before because reagents that specifically recognize NR2C-containing receptors are non-existent. We identified a transition zone from NR2C-expressing neurons to astrocytes in an area connecting the retrosplenial cortex and hippocampus. We demonstrate that NR2C is expressed in a subset of S100beta-positive/GFAP-negative glial cells in the striatum, olfactory bulb and cerebral cortex. We also demonstrate novel areas of neuronal expression such as retrosplenial cortex, thalamus, pontine and vestibular nuclei. In addition, we show that during cerebellar development NR2C is expressed in transient caudal rostral gradients and parasagittal bands in subsets of granule cells residing in the internal granular layer, further demonstrating heterogeneity of granule neurons. These results point to novel functions of NR2C-containing NMDA receptors. PMID- 17276698 TI - Spatial distribution of active muscle fibre characteristics in the upper trapezius muscle and its dependency on contraction level and duration. AB - The aim of this study was to provide direct in vivo information of the physiological and structural characteristics of active muscle fibres from a large part of the upper trapezius muscle. Two-dimensional (2-D) multi-channel surface electromyography recordings were used, with 13 x 10 electrodes covering 6 x 4.5 cm of the skin's surface. A previously developed method was applied to detect individual propagating motor unit action potentials and to estimate their corresponding muscle fibre conduction velocity (MFCV) and muscle fibre orientation (MFO). Using these estimates, spatial distributions of MFCV and MFO were examined for five male subjects performing isometric shoulder elevation at different force levels. The main results were: (1) the general relationship between MFCV and force generation was non-systematic, with a positive relationship at the inferior part of the muscle, (2) the spatial distribution of MFCV at different force levels and fatigue was inhomogeneous and (3) the MFO was slightly different (6 degrees ) of the muscle fibres with origin superior compared to inferior to the C7 vertebra. These findings provide new information of the MFO of contracting muscle fibres and knowledge of the physiological characteristics of a large part of the upper trapezius muscle that previously was based on observations from human cadavers only. PMID- 17276699 TI - Metabolic mapping using 2D 31P-MR spectroscopy reveals frontal and thalamic metabolic abnormalities in schizophrenia. AB - (31)Phosphorus magnetic resonance spectroscopy ((31)P-MRS) allows in vivo investigation of cerebral phospholipid and energy metabolism. Using 2D chemical shift imaging, this method can be applied to study multiple brain areas and to assess concentrations of both phospholipids and high-energy phosphates. The purpose of our study was to assess multiregional metabolic profiles in schizophrenia using a 2D-resolved MRS technique, and to assess the intercorrelation of findings. We applied (31)P-MRS chemical shift imaging in 31 schizophrenia patients (12 antipsychotic-naive first-episode and 19 antipsychotic free multi-episode patients) and 31 healthy age- and sex-matched controls. Spatially resolved maps were compared for the main metabolites of the (31)P spectrum. Metabolites of phospholipid (PME and PDE) and energy (PCr and Pi) metabolism were significantly reduced in bilateral prefrontal and medial temporal (including hippocampal) brain regions, caudate nucleus, thalamus and anterior cerebellum as compared to controls. Moreover, factor analysis of these changes showed a characteristic spatial pattern of changes, which demonstrates significant associations between alterations of phospholipid and energy metabolism, and between metabolic alterations and severity of symptoms (BPRS total score, but not SANS or SAPS scores). This suggests a pattern of intercorrelated changes of these metabolic markers. Results support the notion of disturbed phospholipid turnover in schizophrenia, probably unrelated to prior pharmacological treatment, and associated with increased energy demand. PMID- 17276700 TI - Testing morphology-based hypotheses of phylogenetic relationships in Parmeliaceae (Ascomycota) using three ribosomal markers and the nuclear RPB1 gene. AB - Parmeliaceae is the largest family of lichen-forming fungi with more than 2000 species and includes taxa with different growth forms. Morphology was widely employed to distinguish groups within this large, cosmopolitan family. In this study we test these morphology-based groupings using DNA sequence data from three nuclear and one mitochondrial marker from 120 taxa that include 59 genera and represent the morphological and chemical diversity in this lineage. Parmeliaceae is strongly supported as monophyletic and six well-supported main clades can be distinguished within the family. The relationships among them remain unresolved. The clades largely agree with the morphology-based groupings and only the placement of four of the genera studied is rejected by molecular data, while four other genera belong to clades previously unrecognised. The classification of these previously misplaced genera, however, has already been questioned by some authors based on morphological evidence. These results support morphological characters as important for the identification of monophyletic clades within Parmeliaceae. PMID- 17276701 TI - A phosphorimager-based filter binding thyroid hormone receptor competition assay for chemical screening. AB - INTRODUCTION: A phosphorimager-based filter binding thyroid hormone receptor (THR) competition assay has been developed for use in verifying hits from compound library screens. METHODS: This method employs in vitro translated ligand binding domains (LBDs) of THRalpha and THRbeta, separation through nitrocellulose via a 96-well vacuum manifold, and analysis of receptor-bound radioactivity by phosphorimaging. RESULTS: A standard curve of [I(125)]T3 showed a linear response over the dynamic range of a competition assay, and a comparison of Sephadex G-25 column separation and gamma counting with en masse filtration and phosphorimaging revealed similar IC(50) and K(i) values when using unlabeled T3 as competitor. In addition, this method produced IC(50) and K(i) values for the known T3 competitors [3,5-Dimethyl-4-(4'-hydoxy-3'-isopropylbenzyl) phenoxy] acetic acid (GC-1) and 3,5-diiodothyropropionic acid (DITPA) similar to those reported elsewhere. DISCUSSION: These data suggest that filtration and phosphorimaging adequately and properly reproduces binding values associated with THR competition. Further, this method gave a 3-fold reduction in time and a 40-fold reduction in radioactive waste over the column-based method. These reductions allow for a substantial increase in assay throughput. Taken together, these data suggest that en masse filtration and phosphorimaging is an efficient and tractable method for verifying large groups of putative T3 competitors in vitro. PMID- 17276702 TI - Proximal radial fracture after revision of distal biceps tendon repair: a case report. PMID- 17276703 TI - Effect of mid-late mouse fetus' microenvironment on the growth of tumor cells after intrauterine transplantation. AB - Successful intrauterine transplantation (IUT) of stem cells for treatment of fetal defects in some animal models of human diseases has prompted us to study the mechanisms of transplantation, immunological tolerance and embryonic environment. The objective of this study was to determine whether intrauterine transplantation of tumor cells would affect the survival and growth of the tumor cells themselves as well as fetus development. A total of 2 x 10(6) H(22) cells or S(180) cells were transplanted into the amniotic or abdominal cavity of NIH mice on D9-D12 or D13-D18 of gestation. The adult and newborn NIH mice which were inoculated with the same number of H(22) cells and S(180) cells by intraperitoneal injection were used as positive controls for the cancer bearing control group while undisrupted fetuses of the same gestation were used as negative controls (i.e. for the normal development) group. The development of fetuses transplanted with tumor cells in utero was monitored by several developmental indices, and the tumor growth of them were observed by some distinctive bearing cancer index. The H(22) transplanted group was further assessed for minimal cancer bearing by detection of alpha-fetoprotein (AFP) using radioimmunoassay (RIA) and reverse transcription-polymerase chain reaction (RT PCR). In addition, tumor burden and the development of the F1 generation of the mice by IUT were also investigated. Protein kinase C (PKC) and proliferating cell nuclear antigen (PCNA) of GFP-expressing H(22) cells transplanted in the uterus were analyzed under laser confocal microscopy. There was no significant difference in the developmental indices between the experimental and control groups. HE staining of the major organs, including liver, kidney, and lung, showed that these organs properly developed. No tumor ascites were found in those delivered mice after intrauterine transplantation with H(22) cells and S(180) cells. Furthermore, as minimal bearing cancer index for H(22) cells, AFP expression analyzed by RIA and RT-PCR indicated that no tumor cells were detected in the experimental groups. The F1 progenies developed normally without any signs of tumor development. Fluorescence analysis revealed that expression of PKC and PCNA was markedly reduced in the H(22) cells after injection for 24, 48, and 72 h. Our study showed that the tumor cells did not grow in the mice by intrauterine transplantation, whereas transplantation of the same number of tumor cells resulted in obvious ascites tumor in the adult and newborn mice. Furthermore, the differentiation and proliferation of H(22) cells changed dramatically after injection. Our results suggest that, while the embryonic transplantation of tumor cells does not affect fetal development, the survival and growth of implanted tumor cells may be significantly inhibited in the embryonic microenvironment. PMID- 17276705 TI - The genetic basis of abdominal aortic aneurysms: a review. AB - INTRODUCTION: The pathogenesis of abdominal aortic aneurysm (AAA) remains poorly understood, however significant evidence has emerged in recent years to suggest a chronic inflammatory process. Observational studies have highlighted a familial trend towards AAA development among relatives of affected individuals and it is thought that inflammatory genes may influence an individual's susceptibility. Conflicting reports exist over single gene versus multiple gene inheritance patterns in addition to a collection of studies examining individual inflammatory genes. This paper reviews the evidence for a genetic predisposition to aneurysm formation including familial and segregation studies in addition to experimental evidence investigating specific candidate genes. METHOD: Medline and Pubmed database searches were conducted using the search terms abdominal aortic aneurysm and gene. Papers were reviewed and references manually searched for further relevant publications which were added to the data. Papers were categorised under the headings familial, segregation and candidate gene studies. RESULTS: A review of 58 papers is presented under sub-headings as above. In the case of the candidate gene section, a brief report of the functional relevance of each gene is included. CONCLUSION: A summary of the evidence presented is given and the direction of future work in this field is briefly considered. PMID- 17276704 TI - Susceptibility to induction of long-term depression is associated with impaired memory in aged Fischer 344 rats. AB - The current study employed aged and young male Fischer 344 rats to examine the relationship between long-term depression (LTD), age, and memory. Memory performance was measured on two tasks that are sensitive to hippocampal function; inhibitory avoidance and spatial discrimination on the Morris water maze. The slope of the extracellular excitatory postsynaptic field potential was recorded from CA3-CA1 synapses in hippocampal slices. Low frequency stimulation (LFS) induced a modest LTD only in aged animals under standard recording conditions. The decrease in synaptic transmission examined only in aged animals correlated with memory scores on the spatial task and LTD was not observed in aged animals with the highest memory scores. LTD induction was facilitated by increasing the Ca(2+)/Mg(2+) ratio of the recording medium or employing a paired-pulse stimulation paradigm. Age differences disappeared when LFS was delivered under conditions of elevated Ca(2+)/Mg(2+) in the recording medium. Using multiple induction episodes under conditions which facilitate LTD-induction, no age related difference was observed in the maximum level of LTD. The results indicate that the increased susceptibility to LTD induction is associated with impaired memory and results from a shift in the induction process. The possible relationship between LTD and memory function is discussed. PMID- 17276706 TI - Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. AB - The ferroportin (FPN1) Q248H polymorphism has been associated with increased serum ferritin (SF) levels in sub-Saharan Africans and in African Americans (AA). AA participants of the HEIRS Study who did not have HFE C282Y or H63D who had elevated initial screening SF (> or =300 microg/L in men and >= or =200 microg/L in women) (defined as cases) were frequency-matched to AA participants with normal SF (defined as controls) to investigate the association of the Q248H with elevated SF. 10.4% of cases and 6.7% of controls were Q248H heterozygotes (P=0.257). Q248H homozygosity was observed in 0.5% of the cases and none of the controls. The frequency of Q248H was higher among men with elevated SF than among control men (P=0.047); corresponding differences were not observed among women. This appeared to be unrelated to self-reports of a previous diagnosis of liver disease. Men with elevated SF were three times more likely than women with elevated SF to have Q248H (P=0.012). There were no significant differences in Q248H frequencies in men and women control participants. We conclude that the frequency of the FPN1 Q248H polymorphism is greater in AA men with elevated SF than in those with normal SF. PMID- 17276707 TI - Enhancer identification through comparative genomics. AB - With the availability of genomic sequence from numerous vertebrates, a paradigm shift has occurred in the identification of distant-acting gene regulatory elements. In contrast to traditional gene-centric studies in which investigators randomly scanned genomic fragments that flank genes of interest in functional assays, the modern approach begins electronically with publicly available comparative sequence datasets that provide investigators with prioritized lists of putative functional sequences based on their evolutionary conservation. However, although a large number of tools and resources are now available, application of comparative genomic approaches remains far from trivial. In particular, it requires users to dynamically consider the species and methods for comparison depending on the specific biological question under investigation. While there is currently no single general rule to this end, it is clear that when applied appropriately, comparative genomic approaches exponentially increase our power in generating biological hypotheses for subsequent experimental testing. It is anticipated that cardiac-related genes and the identification of their distant-acting transcriptional enhancers are particularly poised to benefit from these modern capabilities. PMID- 17276710 TI - Epileptic encephalopathy with bilateral continuous spike-waves during slow sleep in a child with vacuolating megalencephalic leukoencephalopathy. AB - This case report describes the clinical evolution of a symptomatic epileptic encephalopathy with bilateral continuous spike-waves during slow wave sleep (BCSWS) in a 3-year-old girl. Her epilepsy with focal motor seizures during sleep was later complicated by myoclonic, atonic and clonic seizures culminating in BCSWS. The clinical picture, clinical course and magnetic resonance imaging findings were characterstic of primary white matter disease, probably, vacuolated megalencephalic leukoencephalopathy with subcortical cysts (MLC). To the best of our knowledge, this is the first reported case of BSCWS in a patient with leukodystrophies or MLC. This case report indicates that epileptic encephalopathy with BSCWS may be a cause of neurological or neuropsychological deterioration in MLC. PMID- 17276709 TI - Characterization of a new gene (SLC10) with a spliced leader from Taenia solium. AB - An unknown gene, SLC10, was cloned by spliced leader-based polymerase chain reaction from Taenia solium. The full length of SLC10 was found to be 635 bp, encoding an 18.223 kDa protein. ELISA results showed that none of 70 normal and 75 cysticercosis sera samples reacted with purified recombinant SLC10 protein. Using an immunohistochemical method, it was revealed that the native SLC10 protein distributed extensively in inner cyst walls but not in the scolex in Cysticercus cellulosae. Together with predicted results, it is suggested that the SLC10 protein is a non-secretory structural protein, which is not involved in induction of the host's immune reactions against infection at least at the larval stage. PMID- 17276708 TI - Transcriptional pathways in second heart field development. AB - The heart is the first organ to form and function during vertebrate development and is absolutely essential for life. The left ventricle is derived from the classical primary or first heart field (FHF), while the right ventricle and outflow tract are derived from a distinct second heart field (SHF). The recent discovery of the SHF has raised several fundamental and important questions about how the two heart fields are integrated into a single organ and whether unique molecular programs control the development of the two heart fields. This review briefly highlights the contributions of the SHF to the developing and mature heart and then focuses primarily on our current understanding of the transcriptional pathways that function in the development of the SHF and its derivatives. PMID- 17276711 TI - Coinheritance of mutated SMN1 and MECP2 genes in a child with phenotypic features of spinal muscular atrophy (SMA) type II and Rett syndrome. AB - Spinal muscular atrophy (SMA) is a neuromuscular autosomal recessive disease characterized by progressive muscle weakness and atrophy combined with motor neuron degeneration caused by mutations in the SMN 1 gene locus (5q11.2-13.2). Rett syndrome (RS) is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2 (Xq28) and characterized by normal development until 6-12 months of age, followed by regression with loss of acquired skills, gradual onset of microcephaly, stereotypic hand movements and psychomotor delay. We report a 6 year-old girl who, at 2 years of age, presented with hypotonia, psychomotor delay, amyotrophy and areflexia of the lower extremities. Molecular DNA analysis (PCR-RFLP's) for SMA type II revealed that both exons 7 and 8 of SMN 1 gene were deleted. Over the past 4 years, onset of stereotypic hand-washing movements, epileptic seizures, microcephaly, hyperventilation/breath-holding attacks and severe psychomotor delay raised the suspicion of the coexistence of RS. DNA analysis (DGGE and sequencing) identified the hotspot missense mutation R306C (c.916C>T) in exon 4 of the MECP2 gene. The coinheritance of SMA and RS, two rare monogenic syndromes in the same patient, has not been previously reported. Thorough clinical evaluation in combination with DNA analysis, allowed accurate diagnosis, providing valuable information for the genetic counseling of the family. PMID- 17276712 TI - Regulation of stromal cell-derived factor-1 and exhaled nitric oxide in asthmatic children following montelukast and ketotifen treatment. AB - BACKGROUND: Montelukast and ketotifen are oral anti-allergy medications in asthmatic children. This study investigates the modulation effect of montelukast and ketotifen on children with intermittent to mild persistent asthma as demonstrated by the levels of peak expiratory flow (PEF), asthma scores (AS), exhaled nitric oxide (eNO) and plasma stromal cell-derived factor-1 (SDF-1) concentration in a randomized, prospective study. METHODS: Fifty asthmatic children were enrolled and received 8 weeks of treatment with oral montelukast sodium 5mg chewable tablet administered once daily, or 1mg ketotifen, and were followed for a 4-week post-treatment washout period. ENO concentration, AS and PEF were measured before, 2, 4, 6 and 8 weeks after initial treatment, and 4 weeks after cessation of treatment. RESULTS: Montelukast therapy was showed to improve AS, PEF and eNO within 2 weeks and remained the improvement during the treatment period. Montelukast also significantly decreased plasma SDF-1 levels after 8 weeks of treatment. In contrast, the ketotifen treatment revealed no significant effects in these clinical parameters until 4 and 6 weeks of the therapy, and did not suppress plasma SDF-1 levels after 8 weeks of treatment. To prove whether montelukast directly suppressed SDF-1 induction, we studied effects of montelukast on the LPS-induced SDF-1 expression and SDF-1-induced chemotaxis of monocytic (THP-1) cells. Montelukast, but not ketotifen, could suppress SDF-1 expression and its related chemotaxis on THP-1 monocytic cells. CONCLUSIONS: Leukotriene receptor antagonist, such as montelukast, may be a better non-steroid anti-inflammatory drug for mild childhood asthma in preventing airway inflammation. PMID- 17276713 TI - Substance P and acetylcholine are co-localized in the pathway mediating mucociliary activity in Rana pipiens. AB - Mucociliary activity is an important clearance mechanism in the respiratory system of air breathing vertebrates. Substance P (SP) and acetylcholine play a key role in the stimulation of the mucociliary transport in the frog palate. In this study, retrograde neuronal tracing was combined with immunocytochemistry for SP and choline acetyl transferase (ChAT) in the trigeminal ganglion and for neurokinin-1 receptor (NK1R) in the palate of Rana pipiens. The cells of origin of the palatine nerve were identified in the trigeminal ganglion using the retrograde tracer Fluorogold (FG). Optimal labeling of FG cells in the trigeminal ganglion was obtained at 96 h of exposure. Immunoflorescent shows that SP and acetylcholine are co-localized in 92% of the cells labeled with FG in the trigeminal ganglion. NK1 receptors were found in the membrane of epithelial and goblet cells of the palate. Ultrastructural study of the palate showed axonal like endings with vesicles in connection with epithelial and goblet cells. These results further support the concerted action of both neurotransmitters in the regulation of mucociliary activity in the frog palate. PMID- 17276714 TI - Purification and characterization of calpain and calpastatin from rainbow trout, Oncorhynchus mykiss. AB - Although the calpain system has been studied extensively in mammalian animals, much less is known about the properties of mu-calpain, m-calpain, and calpastatin in lower vertebrates such as fish. These three proteins were isolated and partly characterized from rainbow trout, Oncorhynchus mykiss, muscle. Trout m-calpain contains an 80-kDa large subunit, but the approximately 26-kDa small subunit from trout m-calpain is smaller than the 28-kDa small subunit from mammalian calpains. Trout mu-calpain and calpastatin were only partly purified; identity of trout mu calpain was confirmed by labeling with antibodies to bovine skeletal muscle mu calpain, and identity of trout calpastatin was confirmed by specific inhibition of bovine skeletal muscle mu- and m-calpain. Trout mu-calpain requires 4.4+/-2.8 microM and trout m-calpain requires 585+/-51 microM Ca(2+) for half-maximal activity, similar to the Ca(2+) requirements of mu- and m-calpain from mammalian tissues. Sequencing tryptic peptides indicated that the amino acid sequence of trout calpastatin shares little homology with the amino acid sequences of mammalian calpastatins. Screening a rainbow trout cDNA library identified three cDNAs encoding for the large subunit of a putative m-calpain. The amino acid sequence predicted by trout m-calpain cDNA was 65% identical to the human 80-kDa m-calpain sequence. Gene duplication and polyploidy occur in fish, and the amino acid sequence of the trout m-calpain 80-kDa subunit identified in this study was 83% identical to the sequence of a trout m-calpain 80-kDa subunit described earlier. This is the first report of two isoforms of m-calpain in a single species. PMID- 17276715 TI - Bacterial expression and characterization of molluscan IDO-like myoglobin. AB - The indoleamine 2,3-dioxygenase (IDO)-like myoglobin (Mb) is a unique type of Mb isolated from the buccal mass of several archgastropod species. Here, we expressed Sulculus diversicolor IDO-like Mb as a GST-fusion protein in bacteria. The visible spectrum of GST-fusion IDO-like Mb shows characteristic alpha- and beta-peaks, indicating that it binds oxygen. To identify residues important in heme and oxygen binding, we constructed site-directed mutants. We initially replaced each of the 7 histidines of S. diversicolor IDO-like Mb with alanine. The spectra of three mutants (H74A, H288A, and H332A) revealed a remarkable loss of absorbance around 414 nm, indicating that they cannot bind heme. His(74), His(288), and His(332) were also replaced by arginine or tyrosine. Neither H332R nor H332Y contains heme, suggesting that His(332) is the proximal ligand of IDO like Mb. In contrast, both H74R and H288Y mutants were isolated in the heme binding oxy-form. The autoxidation rates of these two mutants showed that they can bind oxygen as stably as wild-type. His(74) and His(288) might be partially associated with heme-binding, but do not act as the distal ligand. The S. diversicolor IDO-like Mb seems to stably bind oxygen in a different manner from normal myoglobins. PMID- 17276716 TI - Identification and quantification of histidine-rich glycoprotein (HRG) in the blood plasma of six marine bivalves. AB - Histidine-rich Glycoprotein (HRG) is a metal-binding protein described from the blood plasma of a pteriomorph bivalve, the marine mussel Mytilus edulis L. We demonstrate here, using Cd-Immobilized Metal Affinity Chromatography (IMAC), SDS PAGE, Western Blotting, and ELISA, that HRG is present in three additional pteriomorphs and two heterodont bivalves. ELISA indicates that HRG is the predominant blood plasma protein in all six species (41 to 61% of total plasma proteins by weight). Thus, HRG appears to be a widespread metal-binding protein in the plasma of bivalves. PMID- 17276717 TI - Effects of gonadotropin-releasing hormone analog (GnRHa) on steroidogenic factor 1 (SF-1) and estrogen receptor beta (ERbeta) gene expression in the black porgy (Acanthopagrus schlegeli). AB - We examined effects of GnRHa on expression of steroidogenic factor-1 (SF-1) and estrogen receptor beta (ERbeta) in the pituitary and gonad of protandrous black porgy (Acanthopagrus schlegeli). Fish were intraperitoneally injected with 0.2 microg GnRHa/g fish and then pituitary, gonad and plasma were sampled at 0, 6, 12, 24 and 48 h after injection. In gonad, the mRNA levels of the SF-1 were high at 6 h post injection, and then continuously decreased until 24 h; high expression of ERbeta mRNA levels was only observed at 12 h. In contrast, pituitary SF-1 mRNA levels were very low during the experimental period. GnRHa stimulation caused a significant increase of plasma testosterone (T) and estradiol-17beta (E(2)) after 24 h. We suggest that SF-1 and ERbeta play an important role in the development of gonad and these genes are involved with sex change in fish. PMID- 17276718 TI - Comparison of dinner with bedtime administration of insulin glargine in type 1 diabetic patients treated with basal-bolus regimen. AB - OBJECTIVE: To establish the equivalence in efficacy (HbA(1c)) of insulin glargine injected at dinner versus bedtime in a large number of patients with type 1 diabetes using a fast-acting analogue (FAA) or regular human insulin (RHI) as prandial insulin in an insulin glargine-bolus regimen. RESEARCH DESIGN AND METHODS: In a 26-week trial, 1178 patients with type 1 diabetes and treated with different basal-bolus regimens were randomized to receive insulin glargine once daily at dinner (n=589) or at bedtime (n=589) while continuing their previous prandial insulin (FAA: 75%; RHI: 25% of patients). The primary objective was to demonstrate equivalence in terms of HbA(1c) levels at endpoint. RESULTS: Baseline characteristics were similar in the two groups. At endpoint, HbA(1c) (mean+/ standard deviation [S.D.]) had decreased by 0.25+/-0.66% to 7.77+/-0.96% in the dinnertime group (P<0.0001), and by 0.24+/-0.76% to 7.83+/-1.07% in the bedtime group (P<0.0001). The HbA(1c) difference between dinner and bedtime was -0.022% (two-sided 90% confidence interval [CI] -0.09; 0.05), demonstrating statistical equivalence of HbA(1c) at endpoint between the two groups. Equivalence was also demonstrated within prandial groups: HbA(1c) difference between dinner and bedtime was -0.03% (two-sided 90% CI: -0.11; 0.06) for FAAs and -0.04% (two-sided 90% CI: -0.19; 0.11) for RHIs. The incidence of severe hypoglycaemia did not differ between the treatment groups. CONCLUSION: These data confirm that insulin glargine in combination with either FAA or RHI is equally effective and safe, whether it is administered at dinner or bedtime. PMID- 17276720 TI - Fluorescent in situ hybridization (FISH) in bone marrow and peripheral blood of leukemia patients: implications for occupational surveillance. AB - Although there has been a rapid rise in the application of fluorescent in situ hybridization (FISH) analysis of bone marrow tissue for the staging and prognosis determination of hematopoietic malignacies such as the chronic and acute leukemias, it's application as a surveillance tool for leukemogen exposed high risk occupational cohorts is understandably limited by the invasiveness of sample collection. While some small occupational studies have been performed using FISH in peripheral blood with promising results, some of the basic assumptions made in utilizing the FISH technique have not been fully explored. These include selection of the correct hematopoietic cell to assay (myeloid or lymphoid); selection of appropriate chromosomal markers and the sensitivity of peripheral blood FISH in detecting unbalanced genomic abnormalities. In this study, we performed a pilot 'validation' exercise utilizing the FISH technique and standard metaphase cytogenetics, comparing results in tandem pairs of peripheral blood with bone marrow cells, where clonal abnormalities arise. Samples were taken from patients with known chromosomal lesions associated with active leukemia. We carefully chose markers most frequently associated with leukemogen-inducing DNA damage and probes that have been utilized successfully in clinical practice. Ten de novo or therapy-related acute myeloid leukemia (t-AML) patients underwent bone marrow cell karyotyping and fluorescent in situ hybridization (FISH) analysis. Parallel peripheral blood samples were concommitently drawn and evaluated with FISH using the same probes. In six of eight paired samples treated with a 3-day phytohemagglutinin (PHA) stimulation, typically used to assay lymphocytes and their progenitors, we detected abnormal clones. In one of the two remaining cases, we identified an abnormal clone in both bone marrow and PHA-stimulated peripheral blood, although at a level in the peripheral blood sample that would typically be reported as "non-diagnostic" for clinical purposes. These results suggest that use of FISH in PHA stimulated peripheral blood samples with probes commonly employed in t-AML evaluations (chromosomes 5q, 7q, 8, 11q) to detect cytogenetic abnormalities in peripheral blood represents a potentially promising though as yet, under-utilized approach for the occupational surveillance of workers exposed to leukemogens, especially if it could be linked to automated high-throughput assays for increased sensitivity. PMID- 17276721 TI - A flow injection sampling resonance light scattering system for total protein determination in human serum. AB - A novel flow injection method with resonance light scattering detection was developed for the determination of total protein concentrations. This method is based on the enhancement of RLS signals from Methyl Blue (MB) by protein. The enhanced RLS intensities at 333 nm, in a pH 4.1 acidic aqueous solution, were proportional to the protein concentration over the range 2.0-37.3 and 1.0-36.0 microg ml-1 for human serum albumin (HSA) and bovine serum albumin (BSA), respectively. The corresponding limits of detection (3sigma) of 45 ng ml-1 for HSA and 80 ng ml-1 for BSA were attained. The method was successfully applied to the quantification of total proteins in human serum samples, the maximum relative error is less than 1% and the recovery is between 98% and 102%. The sample throughput was 60 h-1. PMID- 17276722 TI - Cooperative energy transfer frequency upconversion in Tb3+/Yb3+-codoped oxyfluoride glasses. AB - In this report, we investigate the cooperative energy transfer frequency upconversion in Tb3+/Yb3+-codoped SiO2-Al(2)O(3)-Na2O-ZnF(2) oxyfluoride glasses under 980 nm diode laser excitation. The influence of both Tb3+ and Yb3+ concentration on the emission bands were investigated. With a lower Tb3+ concentration, the emission bands around 381, 416 and 438 nm, and 489, 545, 587 and 623 nm associated with (5)D(3), (5)G(6)-->(7)F(J) (J=6, 5, 4) and (5)D(4)- >(7)F(J) (J=6, 5, 4, 3) transitions were observed. However, only (5)D(4)- >(7)F(J) (J=6, 5, 4, 3) transitions appear in a higher Tb3+ concentration. The integrated upconversion luminescence intensity was examined when the temperature of sample was varied from 40 to 450 K. The dependence of the upconversion emission intensity upon the excitation power was also examined, and the upconversion mechanisms were discussed. PMID- 17276724 TI - Enhanced fluorescence of 3-(naphthalene-2-ylimino)-1-phenylbutan-1-one-Tb with 1,10-phenanthroline ternary system and its analytical application. AB - A new Schiff base ligand: 3-(naphthalene-2-ylimino)-1-phenylbutan-1-one (NPB) was synthesized. Its fluorescence intensity with terbium(III) was greatly enhanced by the addition of 1,10-phenanthroline (Phen) in the chloroform solution. The mechanism of fluorescence enhancement was studied. The results indicate the formation of a ternary NPB-Phen-Tb complex. In the ternary system, Phen can transfer the energy absorbed by Phen and NPB to Tb(3+). PMID- 17276723 TI - The study of resonance Raman scattering spectrum on the surface of Cu nanoparticles with ultraviolet excitation and density functional theory. AB - Cu colloid was prepared by oxidation-reduction; it was relatively steady in fixed conditions, with size about 10-30 nm. The Raman spectrum of p-hydroxybenzoic acid (PHBA) in Cu colloid solution with the ultraviolet (UV) excitation at 325 nm, was obtained, even it is usually difficult to obtain Raman signals in Ag or Au in the UV region. It was found that the Raman signal intensities result from the resonance enhanced of surface plasmon resonance of Cu nanoparticles excited at 325 nm. The adsorption behavior of PHBA on the Cu nanoparticles was studied by combining with density functional theory (DFT); it was found that the calculated Raman frequencies were in good agreement with experimental value. So one can conclude that the simplified model is probably reasonable to describe some resonance Raman experiments. PMID- 17276725 TI - Synthesis and spectroscopic properties of rare earth picrate complexes with a new biphenylamide. AB - The new ligand N-benzyl-2-{2'-[(benzyl-ethyl-carbamoyl)-methoxy]-biphenyl-2 yloxy}-N-ethyl-acetamide (L) and its complexes of rare earth picrates were synthesized. The complexes were characterized by elemental analysis, IR, UV-vis spectra and conductivity measurements. The fluorescence properties of the europium complex in solid state and in CHCl(3), ethyl acetate, acetone, acetonitrile and DMF were investigated. Under the excitation, the europium complex exhibited characteristic emissions of europium. The lowest triplet state energy level of the ligand indicates that the triplet state energy level of the ligand matches better to the resonance level of Eu(III) than Tb(III) ion. PMID- 17276726 TI - Diacylglycerol kinase alpha suppresses tumor necrosis factor-alpha-induced apoptosis of human melanoma cells through NF-kappaB activation. AB - We investigated the implication of diacylglycerol kinase (DGK) alpha (type I isoform) in melanoma cells because we found that this DGK isoform was expressed in several human melanoma cell lines but not in noncancerous melanocytes. Intriguingly, the overexpression of wild-type (WT) DGKalpha, but not of its kinase-dead (KD) mutant, markedly suppressed tumor necrosis factor (TNF)-alpha induced apoptosis of AKI human melanoma cells. In the reverse experiment, siRNA mediated knockdown of DGKalpha significantly enhanced the apoptosis. The overexpression of other type I isoforms (DGKbeta and DGKgamma) had, on the other hand, no detectable effects on the apoptosis. These results indicate that DGKalpha specifically suppresses the TNF-alpha-induced apoptosis through its catalytic action. We found that the overexpression of DGKalpha-WT, but not of DGKalpha-KD, further enhanced the TNF-alpha-stimulated transcriptional activity of an anti-apoptotic factor, NF-kappaB. Conversely, DGKalpha-knockdown considerably inhibited the NF-kappaB activity. Moreover, an NF-kappaB inhibitor blunted the anti-apoptotic effect of DGKalpha overexpression. Together, these results strongly suggest that DGKalpha is a novel positive regulator of NF kappaB, which suppresses TNF-alpha-induced melanoma cell apoptosis. PMID- 17276728 TI - Non-ion channel blockers as anti-arrhythmic drugs (reversal of structural remodeling). AB - Approximately 90% of patients with atrial fibrillation have concomitant cardiovascular disease, such as hypertension, heart failure or valve disease. These diseases have been found to substantially affect the structure of atrial tissue, and thereby the occurrence of atrial fibrillation. At the molecular level, angiotensin II, oxidative stress and pro-inflammatory mediators are of particular importance in the induction of pro-arrhthymic atrial dilation, myocardial hypertrophy and interstitial atrial fibrosis. Elucidating the signalling pathways responsible for the process of structural atrial remodeling has helped to define novel non-ion channel drug targets for atrial fibrillation. PMID- 17276727 TI - Effects of anti-hypertensive drugs on vessel rarefaction. AB - The microcirculation largely determines peripheral vascular resistance and substantially contributes to arterial hypertension. In both human arterial hypertension and animal models of hypertension, genetic, fetal and other mechanisms associated with hypertension can reduce the formation and number of microvessels (i.e. parallel-connected arterioles and capillaries). Impaired formation of microvessels (impaired angiogenesis) and microvascular rarefaction can, on the other hand, contribute to increased peripheral resistance and raise blood pressure. Interestingly, drugs targeting the renin-angiotensin-aldosterone system (i.e. angiotensin-converting enzyme inhibitors and AT(1) receptor blockers) induce angiogenesis in vivo in the majority of animal studies. Furthermore, recent clinical studies demonstrate that long-term antihypertensive treatment increases capillary density in the skin of hypertensive patients without diabetes. These effects of angiotensin-converting enzyme inhibitors and AT(1) receptor blockers can be mediated by activation of bradykinin pathways, resulting in the generation of vascular endothelial growth factor, nitric oxide and, consequently, angiogenesis. In conclusion, specific antihypertensive drugs can induce angiogenesis and reduce or even reverse microvascular rarefaction. This might improve target organ damage in, and slow the development of, hypertension. PMID- 17276729 TI - Epac and the cardiovascular system. AB - Exchange protein activated by cyclic AMP (Epac) -- a cyclic AMP-activated guanine nucleotide exchange factor for Ras-like GTPases -- has emerged as a novel mediator of pivotal processes in the cardiovascular system, including cellular calcium handling, hypertrophy, integrin-mediated cell adhesion, establishment of cell polarity, cell migration and endothelial barrier functioning. Epac controls these various cellular responses apparently by signaling to several effector proteins. Spatiotemporal dynamics in the subcellular distribution of Epac-driven signaling networks probably determine the net outcome of cyclic AMP signaling in the cardiovascular system. PMID- 17276730 TI - Regulators of G protein signalling: a spotlight on emerging functions in the cardiovascular system. AB - Regulator of G protein signalling (RGS) proteins are GTPase-activating proteins for heterotrimeric G protein alpha subunits, and are therefore physiologically and pathophysiologically important negative regulators of G-protein-coupled receptor signalling in the cardiovascular system. Owing to the functional redundancy of many of the 20 RGS, and more than 20 RGS-like, proteins even within a single cell, animal models shedding light on the functions of individual RGS proteins are often missing. Nevertheless, RGS2 is a member of this protein family, for which specific functions in the vasculature and the heart are now emerging. Recent data show that the 519-amino acid RGS3, the only RGS protein with an additional G protein betagamma dimer binding domain, largely alters the signalling of G(i) proteins to the monomeric GTPases Rac1 and RhoA in cardiomyocytes. In addition, an alternative approach using transgenic animals expressing RGS-resistant G protein alpha subunits now highlights the contributions of RGS proteins to distinct signalling pathways in the heart. PMID- 17276731 TI - Tipping the gatekeeper: S1P regulation of endothelial barrier function. AB - The lysophospholipid sphingosine 1-phosphate (S1P) is a pleiotropic signaling lipid present constitutively in plasma, and secreted locally at elevated concentrations at sites of inflammation. S1P maintains essential variable homeostatic functions in addition to inducing pathophysiology through the activation of five specific high-affinity G-protein-coupled receptors. Therefore, S1P can function as an extracellular rheostat regulating tonic and acutely evoked functions. Although S1P receptors can regulate lymphoid development and lymphocyte trafficking, and different opinions exist on the roles of receptor agonism and functional antagonism in regulating lymphocyte recirculation, this personal perspective highlights the pivotal control points regulated by constitutive and induced S1P receptor tone at vascular endothelial and lymphatic endothelial barriers, through which S1P agonism impacts on both innate and adaptive immunity. We also emphasize how specific, proof-of-concept chemical tools complement genetic approaches by enabling reversible perturbation of the S1P-S1P(1) receptor axis and, thus, clarifying in vivo mechanisms in the absence of developmental compensations. PMID- 17276732 TI - Therapeutic implications of the TLR and VDR partnership. AB - The innate immune system provides the host with an immediate and rapid defense against invading microbes. Detection of foreign invaders is mediated by a class of receptors that are known as the pattern recognition receptors, such as the family of Toll-like receptors (TLRs). In humans, ten functional TLRs have been identified and they respond to conserved pathogen-associated molecular patterns derived from bacteria, mycoplasma, fungi and viruses. TLR activation leads to direct antimicrobial activity against both intracellular and extracellular bacteria, and induces an antiviral gene program. Recently, it was reported that TLR2 activation leads to the use of vitamin D3 as a mechanism to combat Mycobacterium tuberculosis. Here, we focus on recent findings concerning the TLR induced antimicrobial mechanisms in humans and the therapeutic implications of these findings. Owing to their capability to combat a wide array of pathogens, TLRs are attractive therapeutic targets. However, additional knowledge about their antimicrobial mechanisms is needed. PMID- 17276733 TI - Nature or nurture in mosquito resistance to malaria? AB - The genetic basis of mosquito resistance to malaria parasites is well established and currently receives a lot of attention. However this is not the sole determinant of the success or failure of an infection. In a recent article, Lambrechts and colleagues report the influence of the quality of the external environment of a mosquito on infection. They indicate that external variations could substantially reduce the importance of resistance genes in determining infection by malaria parasites. Furthermore, these variations could influence future plans to use malaria-resistant transgenic mosquitoes to control parasite transmission. PMID- 17276736 TI - Structural methodologies for auditing SNOMED. AB - SNOMED is one of the leading health care terminologies being used worldwide. As such, quality assurance is an important part of its maintenance cycle. Methodologies for auditing SNOMED based on structural aspects of its organization are presented. In particular, automated techniques for partitioning SNOMED into smaller groups of concepts based primarily on relationships patterns are defined. Two abstraction networks, the area taxonomy and p-area taxonomy, are derived from the partitions. The high-level views afforded by these abstraction networks form the basis for systematic auditing. The networks tend to highlight errors that manifest themselves as irregularities at the abstract level. They also support group-based auditing, where sets of purportedly similar concepts are focused on for review. The auditing methodologies are demonstrated on one of SNOMED's top level hierarchies. Errors discovered during the auditing process are reported. PMID- 17276735 TI - Intrinsic ability of GM+IL-4 but not Flt3L-induced rat dendritic cells to promote allogeneic T cell hyporesponsiveness. AB - The influence of GM+IL-4 and Flt3 ligand (FL) on phenotype and function of BM derived DC from Lewis rats was investigated. GM+IL-4-induced DC, despite expression of CD80/CD86, were less stimulatory than FL-induced DC that expressed low CD80/CD86 and were efficient stimulators of allogeneic T cells. GM+IL-4 DC were CD11b+ OX62lo, whereas FL DC were CD11blo OX62+. Following activation, GM+IL 4 DC produced IL-10 and IL-6, but no IL-12p70, and were resistant to further maturation. FL DC produced IL-12p70, IFN-alpha/beta, IL-10 and IL-6 and underwent maturation. Repeated stimulation of T cells with GM+IL-4 DC inhibited proliferation, cytokine production and induced early T cell apoptosis. FL DC activated T cells produced large amounts of IFN-gamma/IL-10 and exhibited late T cell apoptosis/necrosis. In vivo, GM+IL-4 DC induced alloAg-specific hyporesponsiveness following T cell restimulation. These results demonstrate that GM+IL-4 DC display intrinsic regulatory properties, inducing passive-cell-death in T cells with potential for inactivation/regulation of alloreactive T cells in transplantation. PMID- 17276734 TI - The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. AB - In systemic lupus erythematosus, TNFalpha is elevated in the serum and correlates with disease activity and triglyceride levels. The stimuli that drive TNFalpha in this setting are incompletely understood. This study was designed to evaluate monocyte chromatin at the TNFalpha locus to identify semi-permanent changes that might play a role in altered expression of TNFalpha. SLE patients with relatively quiescent disease (mean Physician Global Assessment=0.6) and healthy controls were recruited for this study. TNFalpha expression was measured by intracellular cytokine staining of different monocyte subsets in patients (n=24) and controls (n=12). Histone acetylation at the TNFalpha locus was measured by chromatin immunoprecipitation using a normalized quantitative PCR in patients (n=46) and controls (n=24). There were no differences in the overall fractions of cells expressing CD14 in SLE patients compared to controls; however, the fraction of DR+/CD16+ cells expressing CD14 was slightly higher as was true in the monocyte subset defined by DR+/CD11b+. Within the monocyte population defined by physical characteristics and DR+/CD14+, TNFalpha expressing cells were more frequent in SLE patients compared to controls. Both the fraction of positive cells and the mean fluorescence intensity were higher in patients than controls. Consistent with this was the finding that monocytes from patients had increased TNFalpha transcripts and more highly acetylated histones at the TNFalpha locus compared to controls. Furthermore, patients with the highest levels of TNFalpha histone acetylation were more likely to have had consistently elevated erythrocyte sedimentation rates, and to have required cytotoxic use. Histone acetylation, associated with increased transcriptional competence of TNFalpha, may play a role in certain inflammatory aspects of the disease. PMID- 17276737 TI - Cytoskeletal structure in cells harboring two mutations: R133C in NOTCH3 and 5650G>A in mitochondrial DNA. AB - We have previously described a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) caused by R133C mutation in NOTCH3 and with a concomitant myopathy caused by a G to A point mutation at base pair 5650 (5650G>A) in the gene encoding tRNA(Ala) in mitochondrial DNA (mtDNA). In the present study, we have examined the morphology of the cytoskeletal components in fibroblasts and myoblasts of this patient. Immunolabeling revealed that tubulin network was sparse and formed asters in these cells, whereas no changes were found in actin and vimentin networks in comparison to the control cell lines. Furthermore, mitochondria were less abundant and the branches of the mitochondrial network were reduced in number. Muscle histochemical analysis showed ragged red fibres (RRFs) and cytochrome c oxidase (COX)-negative fibres. The mean proportion of mtDNA with 5650G>A was lower in histologically normal muscle fibres than in the COX-negative fibres and in the RRFs. These findings suggest that 5650G>A is a pathogenic mtDNA mutation. However, the changes in tubulin network and mitochondrial distribution in patient fibroblasts and myoblasts cannot solely be explained by this mutation. PMID- 17276738 TI - CHOP (C/EBP homologous protein) and ASNS (asparagine synthetase) induction in cybrid cells harboring MELAS and NARP mitochondrial DNA mutations. AB - Mitochondrial dysfunction caused by mutations in mitochondrial DNA (mtDNA) is related to a variety of diseases including MELAS and NARP syndromes. However, little is known about the intracellular responses induced by mtDNA mutations. In order to identify genes whose expression is altered as a result of the presence of mtDNA mutations, DNA microarray analysis was performed using human 143B osteosarcoma cells harboring 3243A>G [tRNA-Leu (UUR)] and 8993T>G [ATPase6 Leu156Arg] mtDNA mutations associated with MELAS and NARP syndromes (2SD and NARP3-1 cybrid cells), respectively. We found that mRNA and protein levels of ATF4, CHOP and ASNS were upregulated in 2SD and NARP3-1 cells as compared with parental cells. Reporter assays demonstrated that transcription of CHOP and ASNS genes was upregulated through the AARE (amino acid regulatory element) and NSRE-1 (nutrient-sensing response element-1) enhancer elements to which ATF4 binds, respectively. Furthermore, knockdown of ATF4 by RNA interference reduced CHOP and ASNS transcription in 2SD and NARP3-1 cells. These results suggest that the presence of mtDNA mutations elicits upregulation of CHOP and ASNS genes through the elevation of ATF4 expression and its binding to the AARE and NSRE-1, respectively. PMID- 17276739 TI - MELAS and L-arginine therapy. AB - We investigated the endothelial function in MELAS patients and also evaluated the therapeutic effects of L-arginine. Concentrations of L-arginine during the acute phase of MELAS were significantly lower than in control subjects. L-arginine infusions significantly improved all symptoms suggesting stroke within 30 min, and oral administration significantly decreased frequency and severity of stroke like episodes. Flow-mediated dilation (FMD) in patients showed a significant decrease than those in the controls. Two years of oral supplementation of L arginine significantly improved endothelial function to the control levels and was harmonized with the normalized plasma levels of L-arginine in patients. L arginine therapy showed promise in treating stroke-like episodes in MELAS. PMID- 17276741 TI - Detoxifying function of cytochrome c against oxygen toxicity. AB - The detoxifying function of cytochrome c to scavenge O2-* and H2O2 in mitochondria is confirmed experimentally. A model of respiratory chain operating with two electron-leak pathways mediated by cytochrome c is suggested to illustrate the controlling mechanism of ROS level in mitochondria. A concept of mitochondrial radical metabolism is suggested based on the two electron-leak pathways mediated by cytochrome c are metabolic routes of O2-*. Two portions of oxygen consumption can be found in mitochondria. The main portion of oxygen consumed in the electron transfer of respiratory chain is used in ATP synthesis, while a subordinate part of oxygen consumed by the leaked electrons contributes to ROS generation. It is found that the amount of electron leak of respiratory chain is not fixed, but varies with age and pathological states. The models of respiratory chain operating with two cytochrome c-mediated electron-leak pathways and a radical metabolism of mitochondria accompanied with energy metabolism are helpful to comprehend the pathological problems caused by oxygen toxicity. PMID- 17276740 TI - Diagnostic challenges of mitochondrial DNA disorders. AB - Although mitochondrial disorders are increasingly being recognized, confirming a specific diagnosis remains a great challenge due to the genetic and clinical heterogeneity of the disease. The heteroplasmic nature of most pathogenic mitochondrial DNA mutations and the uncertainties of the clinical significance of novel mutations pose additional complications in making a diagnosis. Suspicion of mitochondrial disease among patients with multiple, seemingly unrelated neuromuscular and multi-system disorders should ideally be confirmed by the finding of deleterious mutations in genes involving mitochondrial biogenesis and functions. The genetics are complex, as the primary mutation can be either in the nuclear or the mitochondrial DNA (mtDNA). MtDNA mutations are often maternally inherited, but can also be sporadic or secondary to mutations in nuclear-encoded mitochondrial-targeted genes. Several well-defined clinical syndromes associated with specific mutations have been described, yet the genotype-phenotype correlation is often unclear and most patients do not fit within any defined syndrome and even within a family the expressivity of the disease can be extremely variable. This article describes examples representing diagnostic challenges of mitochondrial diseases that include the limitations of the mutation detection method, the occurrence of mitochondrial disease in families with another known neuromuscular disorder, atypical clinical presentation, the lack of correlation between the degree of mutant heteroplasmy and the severity of the disease, variable penetrance, and nuclear gene defects causing mtDNA depletion. PMID- 17276742 TI - Screening of common mitochondrial mutations in Chinese patients with mitochondrial encephalomyopathies. AB - To investigate the spectrum of common mitochondrial mutations in Northern China during the years of 2000-2005, 552 patients of mitochondrial encephalomyopathies clinically diagnosed as MELAS, MERRF or Leigh's syndrome, 14 cases of LHON and 46 cases of aminoglycoside induced deafness along with their family members, accepted routine point mutation tests at nucleotide positions 3243, 8344, 8993, 11778 or 1555 in mitochondrial genome. PCR-RFLP analysis, site-specific PCR and PCR-sequencing methods were used to identify the mutations. Fifty-seven cases with A3243G mutation, 4 cases with A8344G, 2 cases with T8993C and 1 case with T8993G were identified from the 552 encephalomyopathy patients. In addition, one case with G11778A was found from the 14 cases of LHON, and 5 cases with A1555G from the 46 cases of aminoglycoside ototoxicity patients. Additional screening for T8356G and T3271C merely had limited significance for the diagnosis of MERRF and MELAS. Differential diagnosis among mitochondrial encephalomyopathies was often complicated due to many similar clinical manifestations. For A3243G mutation, the proportion of mutant mtDNA was not related to severity of the disease but to the age of onset. PMID- 17276743 TI - Hypertension among Polish males during the economic transition. AB - In the late 1980s and early 1990s Polish society experienced deep political, economic and social changes. The aim of the study is to investigate whether changes that occurred in Poland during the transformation significantly influenced the risk of hypertension among adult men. We find that irrespective of age, marital status, education, degree of urbanization, lifestyle variables (smoking, drinking alcohol, and physical activity), and BMI the risk of hypertension after 1989 was higher than before transformation (odds ratio=1.45, p<0.001). Psychosocial factors are proposed as factors which might at least partly explain the higher risk of hypertension during the first years of economic transition in Poland. PMID- 17276744 TI - FGF23 is a hormone-regulating phosphate metabolism--unique biological characteristics of FGF23. AB - FGF23 was identified as the last member of FGF23 family. Recent investigations indicate that excess actions of FGF23 cause several hypophosphatemic diseases whereas deficient FGF23 activity results in hyperphosphatemic tumoral calcinosis. These results indicate that FGF23 is a hormone that regulates serum phosphate level in contrast to other FGF family members that work as local factors. Furthermore, FGF23 requires Klotho for its signaling in addition to a canonical FGF receptor. These unique characteristics of FGF23 expanded our knowledge about the diversity of FGF family members and specificity of FGF23. PMID- 17276745 TI - The rapidly expanding field of autism research. PMID- 17276746 TI - Using the autism diagnostic interview--revised to increase phenotypic homogeneity in genetic studies of autism. AB - BACKGROUND: Many chromosomal regions for susceptibility to autism spectrum disorders (ASDs) have been identified, but few have reached genomewide significance. In response, researchers have attempted to increase the power of their analyses by stratifying samples to increase phenotypic homogeneity. Although homogeneity has typically been defined by a single variable, resultant groups often differ in other dimensions that may be directly pertinent. Group differences in age, gender, IQ, and measures of autism severity are examined as related to Autism Diagnostic Interview-Revised (ADI-R) domains previously used for subsetting or Quantitative Trait Analysis (QTL). METHODS: Participants were research participants and clinic referrals for assessment of possible autism. Assessments included the ADI-R, Autism Diagnostic Observation Schedule, Vineland Adaptive Behavior Scales, and a developmental or cognitive test. Data were collected for 983 individuals, ages 4 to 52 years, with diagnoses of autism and ASDs. RESULTS: Findings suggest that, of several potential grouping variables, only restricted and repetitive behaviors associated with Insistence on Sameness were independent of age, IQ, and autism severity. CONCLUSIONS: Results emphasize the potential unintended effects of stratification and the importance of understanding such interrelationships between phenotypic characteristics when defining subgroups or performing QTL. PMID- 17276747 TI - Evidence for cortical dysfunction in autism: a proton magnetic resonance spectroscopic imaging study. AB - BACKGROUND: Although brain imaging studies have reported neurobiological abnormalities in autism, the nature and distribution of the underlying neurochemical irregularities are unknown. The purpose of this study was to examine cerebral gray and white matter cellular neurochemistry in autism with proton magnetic resonance spectroscopic imaging (MRSI). METHODS: Proton MRSI examinations were conducted in 26 males with autism (age 9.8 +/- 3.2 years) and 29 male comparison subjects (age 11.1 +/- 2.4 years). Estimates of cerebral gray and white matter concentrations of N-acetylaspartate (NAA), creatine + phosphocreatine, choline-containing compounds, myo-inositol, and glutamate + glutamine (Glx) were made by linear regression analysis of multi-slice MRSI data and compared between groups. Regional estimates of metabolite concentration were also made with multivariate linear regression, allowing for comparisons of frontal, temporal, and occipital gray matter, cerebral white matter, and the cerebellum. RESULTS: Patients with autism exhibited significantly lower levels of gray matter NAA and Glx than control subjects. Deficits were widespread, affecting most cerebral lobes and the cerebellum. No significant differences were detected in cerebral white matter or cerebellar metabolite levels. CONCLUSIONS: These results suggest widespread reductions in gray matter neuronal integrity and dysfunction of cortical and cerebellar glutamatergic neurons in patients with autism. PMID- 17276748 TI - Developmental disabilities modification of the Children's Global Assessment Scale. AB - BACKGROUND: Interventions for pervasive developmental disorders (PDD) aim to alleviate symptoms and improve functioning. To measure global functioning in treatment studies, the Children's Global Assessment Scale was modified and psychometric properties of the revised version (DD-CGAS) were assessed in children with PDD. METHODS: Developmental disabilities-relevant descriptors were developed for the DD-CGAS, and administration procedures were established to enhance rater consistency. Ratings of clinical case vignettes were used to assess inter-rater reliability and temporal stability. Validity was assessed by correlating the DD-CGAS with measures of functioning and symptoms in 83 youngsters with PDD. Sensitivity to change was assessed by comparing change from baseline to post-treatment with change on the Aberrant Behavior Checklist Irritability and Clinical Global Impressions-Improvement subscale scores in a subset of 14 children. RESULTS: Inter-rater reliability (intraclass correlation coefficient [ICC] = .79) and temporal stability (average ICC = .86) were excellent. The DD-CGAS scores correlated with measures of functioning and symptoms with moderate to large effect sizes. Changes on the DD-CGAS correlated with changes on the Aberrant Behavior Checklist-I (r = -.71) and Global Impressions Scale-I (r = -.52). The pre-post DD-CGAS change had an effect size of .72. CONCLUSIONS: The DD-CGAS is a reliable instrument with apparent convergent validity for measuring global functioning of children with PDD in treatment studies. PMID- 17276750 TI - Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures. AB - BACKGROUND: Methylphenidate has been shown elsewhere to improve hyperactivity in about half of treated children who have pervasive developmental disorders (PDD) and significant hyperactive-inattentive symptoms. We present secondary analyses to better define the scope of effects of methylphenidate on symptoms that define attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), as well as the core autistic symptom domain of repetitive behavior. METHODS: Sixty-six children (mean age 7.5 y) with autistic disorder, Asperger's disorder, and PDD not otherwise specified, were randomized to varying sequences of placebo and three different doses of methylphenidate during a 4-week blinded, crossover study. Methylphenidate doses used approximated .125, .25, and .5 mg/kg per dose, twice daily, with an additional half-dose in the late afternoon. Outcome measures included the Swanson, Nolan, and Pelham Questionnaire revised for DSM-IV (ADHD and ODD scales) and the Children's Yale-Brown Obsessive Compulsive Scales for PDD. RESULTS: Methylphenidate was associated with significant improvement that was most evident at the .25- and .5-mg/kg doses. Hyperactivity and impulsivity improved more than inattention. There were not significant effects on ODD or stereotyped and repetitive behavior. CONCLUSIONS: Convergent evidence from different assessments and raters confirms methylphenidate's efficacy in relieving ADHD symptoms in some children with PDD. Optimal dose analyses suggested significant interindividual variability in dose response. PMID- 17276751 TI - Elaborative verbal encoding and altered anterior parahippocampal activation in adolescents and young adults at genetic risk for schizophrenia using FMRI. AB - BACKGROUND: First-degree relatives of persons with schizophrenia are at elevated risk for the illness, demonstrate deficits in verbal memory, and exhibit structural abnormalities in the medial temporal lobe (MTL). We used functional magnetic resonance imaging (fMRI) to assess brain activity in the MTL during novel and repeated word-pair encoding. METHODS: Participants were 21 non psychotic, first-degree relatives of persons with schizophrenia and 26 matched healthy controls (ages 13-28). fMRI signal change was measured using a Siemens 1.5T MR scanner, and data were analyzed using SPM-2. Verbal memory was assessed using the Miller Selfridge (MS) Context Memory test prior to scanning. RESULTS: The groups were comparable on demographics, intelligence and post-scan word recognition. Relatives at genetic risk (GR) had significantly more psychopathology than controls and worse performance on the MS test (p < .05). GR participants exhibited greater repetition suppression of activation in the left and right anterior parahippocampus (PHA, in the region of the entorhinal cortex region), after controlling for possible confounders. Controls and GR participants with above-median MS performance showed significantly greater repetition suppression of activation in left inferior frontal gyrus than those scoring below the median. CONCLUSIONS: This is the first study to demonstrate an alteration of brain activity in the PHA in persons at GR for schizophrenia. PMID- 17276753 TI - Resisting prescribing pressure for sildenafil. PMID- 17276752 TI - Stop killing people who kill people. PMID- 17276754 TI - When in doubt, disclose. PMID- 17276749 TI - Early pharmacological treatment of autism: a rationale for developmental treatment. AB - Autism is a dynamic neurodevelopmental syndrome in which disabilities emerge during the first three postnatal years and continue to evolve with ongoing development. We briefly review research in autism describing subtle changes in molecules important in brain development and neurotransmission, in morphology of specific neurons, brain connections, and in brain size. We then provide a general schema of how these processes may interact with particular emphasis on neurotransmission. In this context, we present a rationale for utilizing pharmacologic treatments aimed at modifying key neurodevelopmental processes in young children with autism. Early treatment with selective serotonin reuptake inhibitors (SSRIs) is presented as a model for pharmacologic interventions because there is evidence in autistic children for reduced brain serotonin synthesis during periods of peak synaptogenesis; serotonin is known to enhance synapse refinement; and exploratory studies with these agents in autistic children exist. Additional hypothetical developmental interventions and relevant published clinical data are described. Finally, we discuss the importance of exploring early pharmacologic interventions within multiple experimental settings in order to develop effective treatments as quickly as possible while minimizing risks. PMID- 17276755 TI - Intuitive prosthetic limb control. PMID- 17276756 TI - Haemoglobin targets: we were wrong, time to move on. PMID- 17276757 TI - Sexuality in chronic illness: no longer ignored. PMID- 17276758 TI - Can lethal injection for execution really be "fixed"? PMID- 17276759 TI - Population growth and the Millennium Development Goals. PMID- 17276760 TI - Clarification: human rights abuse and other criminal violations in Port-au Prince, Haiti. PMID- 17276762 TI - Rosemary Basson: working to normalise women's sexual reality. PMID- 17276763 TI - Haemoglobin concentrations in chronic kidney disease. PMID- 17276764 TI - Effect of smoking on lifestyle interventions to prevent diabetes. PMID- 17276767 TI - Methadone and QTc prolongation. PMID- 17276768 TI - Barriers against STDs: what about planned pregnancy? PMID- 17276769 TI - Human papillomavirus vaccine policy. PMID- 17276770 TI - Acute myeloid leukaemia. PMID- 17276771 TI - Health politics: the illegitimate child of health policy. PMID- 17276772 TI - Applied interest-group analysis in reproductive health policy. PMID- 17276773 TI - In praise of Rockefeller. PMID- 17276774 TI - A focus on trees will miss the forest. PMID- 17276775 TI - When the book is wrong. PMID- 17276776 TI - Homeland security reaches the anus. PMID- 17276777 TI - Targeted reinnervation for enhanced prosthetic arm function in a woman with a proximal amputation: a case study. AB - BACKGROUND: The function of current artificial arms is limited by inadequate control methods. We developed a technique that used nerve transfers to muscle to develop new electromyogram control signals and nerve transfers to skin, to provide a pathway for cutaneous sensory feedback to the missing hand. METHODS: We did targeted reinnervation surgery on a woman with a left arm amputation at the humeral neck. The ulnar, median, musculocutaneous, and distal radial nerves were transferred to separate segments of her pectoral and serratus muscles. Two sensory nerves were cut and the distal ends were anastomosed to the ulnar and median nerves. After full recovery the patient was fit with a new prosthesis using the additional targeted muscle reinnervation sites. Functional testing was done and sensation in the reinnervated skin was quantified. FINDINGS: The patient described the control as intuitive; she thought about using her hand or elbow and the prosthesis responded appropriately. Functional testing showed substantial improvement: mean scores in the blocks and box test increased from 4.0 (SD 1.0) with the conventional prosthesis to 15.6 (1.5) with the new prosthesis. Assessment of Motor and Process Skills test scores increased from 0.30 to 1.98 for motor skills and from 0.90 to 1.98 for process skills. The denervated anterior chest skin was reinnervated by both the ulnar and median nerves; the patient felt that her hand was being touched when this chest skin was touched, with near-normal thresholds in all sensory modalities. INTERPRETATION: Targeted reinnervation improved prosthetic function and ease of use in this patient. Targeted sensory reinnervation provides a potential pathway for meaningful sensory feedback. PMID- 17276778 TI - Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. AB - BACKGROUND: Recombinant human erythropoietin is commonly used for treatment of anaemia. Our aim was to determine whether targeting different haemoglobin concentrations with such treatment is associated with altered all-cause mortality and cardiovascular events in patients with anaemia caused by chronic kidney disease. METHODS: We did a meta-analysis of randomised controlled clinical trials that were identified in medical databases and trial registration websites. Trials were eligible for inclusion if they assessed the effects of targeting different haemoglobin concentrations in patients with anaemia caused by chronic disease who were randomly assigned to treatment with recombinant human erythropoietin, recruited at least 100 patients, and had a minimum follow-up of 12 weeks. FINDINGS: We analysed nine randomised controlled trials that enrolled 5143 patients. There was a significantly higher risk of all-cause mortality (risk ratio 1.17, 95% CI 1.01-1.35; p=0.031) and arteriovenous access thrombosis (1.34, 1.16-1.54; p=0.0001) in the higher haemoglobin target group than in the lower haemoglobin target group in the fixed effects model without heterogeneity between studies. There was a significantly higher risk of poorly controlled blood pressure (1.27, 1.08-1.50; p=0.004) in the higher haemoglobin target group than in the lower target haemoglobin group with the fixed effects model; however, this was not significant in the random effects model (1.31, 0.97-1.78; p=0.075). The incidence of myocardial infarction was much the same in the two groups. INTERPRETATION: To target higher haemoglobin concentrations when treating patients with anaemia caused by chronic kidney disease with recombinant human erythropoietin puts such patients at increased risk of death. Current guidelines do not include an upper limit for the target haemoglobin concentration; such an upper limit should be considered in future recommendations. PMID- 17276779 TI - Cost-effectiveness of pneumococcal conjugate vaccination in the prevention of child mortality: an international economic analysis. AB - BACKGROUND: Routine vaccination of infants against Streptococcus pneumoniae (pneumococcus) needs substantial investment by governments and charitable organisations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate these data into an economic analysis of pneumococcal vaccination of infants in countries eligible for financial support from the Global Alliance for Vaccines & Immunization (GAVI). METHODS: We constructed a decision analysis model to compare pneumococcal vaccination of infants aged 6, 10, and 14 weeks with no vaccination in the 72 countries that were eligible as of 2005. We used published and unpublished data to estimate child mortality, effectiveness of pneumococcal conjugate vaccine, and immunisation rates. FINDINGS: Pneumococcal vaccination at the rate of diptheria-tetanus-pertussis vaccine coverage was projected to prevent 262,000 deaths per year (7%) in children aged 3-29 months in the 72 developing countries studied, thus averting 8.34 million disability-adjusted life years (DALYs) yearly. If every child could be reached, up to 407,000 deaths per year would be prevented. At a vaccine cost of International 5 dollars per dose, vaccination would have a net cost of 838 million dollars, a cost of 100 dollars per DALY averted. Vaccination at this price was projected to be highly cost-effective in 68 of 72 countries when each country's per head gross domestic product per DALY averted was used as a benchmark. INTERPRETATION: At a vaccine cost of between 1 dollar and 5 dollars per dose, purchase and accelerated uptake of pneumococcal vaccine in the world's poorest countries is projected to substantially reduce childhood mortality and to be highly cost-effective. PMID- 17276780 TI - Wilson's disease. AB - Progressive hepatolenticular degeneration, or Wilson's disease, is a genetic disorder of copper metabolism. Knowledge of the clinical presentations and treatment of the disease are important both to the generalist and to specialists in gastroenterology and hepatology, neurology, psychiatry, and paediatrics. Wilson's disease invariably results in severe disability and death if untreated. The diagnosis is easily overlooked but if discovered early, effective treatments are available that will prevent or reverse many manifestations of this disorder. Studies have identified the role of copper in disease pathogenesis and clinical, biochemical, and genetic markers that can be useful in diagnosis. There are several chelating agents and zinc salts for medical therapy. Liver transplantation corrects the underlying pathophysiology and can be lifesaving. The discovery of the Wilson's disease gene has opened up a new molecular diagnostic approach, and could form the basis of future gene therapy. PMID- 17276781 TI - Sexual sequelae of general medical disorders. AB - That sexual symptoms can signal serious underlying disease confirms the importance of sexual enquiry as an integral component of medical assessment. Data on sexual function are sparse in some medical specialties. However, increased scientific understanding of the central and peripheral physiology of sexual response could help to identify the pathophysiology of sexual dysfunction from disease and medical interventions, and also to ameliorate or prevent some dysfunctions. Many common general medical disorders have negative effects on desire, arousal, orgasm, ejaculation, and freedom from pain during sex. Chronic disease also interferes indirectly with sexual function, by altering relationships and self-image and causing fatigue, pain, disfigurement, and dependency. Current approaches to assessment of sexual dysfunction are based on models that combine psychological and biological aspects. PMID- 17276782 TI - The eye in hypertension. AB - Hypertension has a range of effects on the eye. Hypertensive retinopathy refers to retinal microvascular signs that develop in response to raised blood pressure. Signs of hypertensive retinopathy are frequently seen in adults 40 years and older, and are predictive of incident stroke, congestive heart failure, and cardiovascular mortality--independently of traditional risk factors. Hypertension is also a major risk factor for the development of other retinal vascular diseases, such as retinal vein and artery occlusion, and ischaemic optic neuropathy. High blood pressure increases the risk of both development of diabetic retinopathy and its progression. Adequate control of blood pressure has been proven in randomised clinical trials to reduce vision loss associated with diabetic retinopathy. Finally, hypertension has been implicated in the pathogenesis of glaucoma and age-related macular degeneration. Recognition of the ocular effects of blood pressure could allow physicians to better manage patients with hypertension, and to monitor its end-organ effects. PMID- 17276783 TI - A bumpy ride to a discarded diagnosis. PMID- 17276784 TI - Will carrots or sticks raise influenza immunization rates of health care personnel? AB - New Joint Commission on the Accreditation of Healthcare Organizations standards require health care organizations to implement staff influenza immunization programs and track employee immunization rates. Although the Centers for Disease Control and Prevention have recommended influenza immunizations for health care workers since 1981, employee vaccination rates have stagnated at 30% to 40% for several years. With the recent attention on these low rates, some institutions have increased employee rates significantly with robust, multifaceted immunization programs. Others have attempted to require immunizations as a condition of employment. Declinations signed by those who refuse immunizations also have been proposed. This article examines recommendations for employee influenza immunizations and the evidence for effective strategies that increase coverage rates. With so much misunderstanding about the influenza immunization, robust interactive education, and onsite, easily accessible vaccination at no cost to employees--the carrots--may be more successful in increasing rates than are declinations and work exclusion--the sticks. Strong immunization programs may create the tipping point for making influenza immunizations as routine in health care as gloves. More robust staff immunization programs, evaluations of their effectiveness, surveillance of health care employee immunization rates, as well as further evidence of effectiveness of declinations and work exclusions should guide further policy formation and implementation. PMID- 17276785 TI - Pandemic influenza: what infection control professionals should know. AB - During the last century, 3 influenza A pandemics have occurred, and pandemic influenza will inevitably occur in the future. Although the timing and severity of the next pandemic cannot be predicted, the probability that a pandemic will occur has increased based on the current outbreaks of A(H5N1) in Asia, Europe, and Africa. Because of these widespread outbreaks, the World Health Organization declared a phase 3 pandemic alert in the fall of 2005. Early detection is essential to prevent the spread of avian influenza. Planning now can be achieved by integrating interventions to ensure a prompt and effective response to a pandemic. This article provides an overview of the current status of A(H5N1) influenza worldwide and recommendations for the prevention and control of avian influenza should it emerge in humans in the United States. PMID- 17276786 TI - Changing health care worker behavior in relation to respiratory disease transmission with a novel training approach that uses biosimulation. AB - BACKGROUND: This pilot study was conducted to determine whether supplementing standard classroom training methods regarding respiratory disease transmission with a visual demonstration could improve the use of personal protective equipment among emergency department nurses. METHODS: Participants included 20 emergency department registered nurses randomized into 2 groups: control and intervention. The intervention group received supplemental training using the visual demonstration of respiratory particle dispersion. Both groups were then observed throughout their work shifts as they provided care during January-March 2005. RESULTS: Participants who received supplemental visual training correctly utilized personal protective equipment statistically more often than did participants who received only the standard classroom training. CONCLUSION: Supplementing the standard training methods with a visual demonstration can improve the use of personal protective equipment during care of patients exhibiting respiratory symptoms. PMID- 17276787 TI - Nurses' attitudes and beliefs about influenza and the influenza vaccine: a summary of focus groups in Alabama and Michigan. AB - BACKGROUND: The U.S. Advisory Committee on Immunization Practices (ACIP) recommends influenza immunization among United States health care workers (HCWs) to reduce the spread of influenza to and from workers and patients. Despite these recommendations, influenza immunization coverage of health care workers is less than 50%. PARTICIPANTS AND METHODS: Eight focus groups of registered nurses (RNs) were conducted in Birmingham, Alabama (n = 34) and Detroit, Michigan (n = 37). In each city, the focus groups consisted of 2 groups each of vaccinated and unvaccinated RNs. RESULTS: These focus groups revealed that many nurses were concerned about influenza vaccine effectiveness and safety; their lack of information about the vaccine plays a part in their willingness to promote it to patients. Unvaccinated nurses tended to be less aware of the ACIP recommendations for HCW vaccination, and overall, nurses were not aware of the rationale for HCW vaccination. Attitudes were mixed regarding mandatory influenza vaccination programs, including the hope that such programs would result in higher vaccination rates and concern about potential disciplinary action if vaccine was declined. Participants believed that increasing convenience was the key to increasing HCW vaccination. CONCLUSIONS: Our findings confirm the importance of comprehensive approaches that combine education and convenience, and suggest that emphasizing the rationale for HCW vaccination may contribute to increasing vaccination rates. PMID- 17276788 TI - Hospital infectious disease emergency preparedness: a survey of infection control professionals. AB - BACKGROUND: Hospital preparedness for infectious disease emergencies is imperative for local, regional, and national response planning. METHODS: A secondary data analysis was conducted of a survey administered to Infection Control Professionals (ICPs) in May, 2005. RESULTS: Most hospitals have ICP representation on their disaster committee, around-the-clock infection control support, a plan to prioritize health care workers to receive vaccine or antivirals, and non-health care facility surge beds. Almost 20% lack a surge capacity plan. Some lack negative pressure rooms for current patient loads or any surge capacity. Less than half have a plan for rapid set-up of negative pressure, and Midwest hospitals are less likely than other areas to have such plans. Smaller hospitals have less negative pressure surge capacity than do larger hospitals. About half have enough health care workers to respond to a surge that involves < or =50 patients; few can handle > or =100 patients. Many do not have sufficient ventilators or can handle < or =10 additional ventilated patients. Most do not have enough National Institute for Occupational Safety and Health approved respirators, and less than half have sufficient surgical masks to handle a significant surge. CONCLUSIONS: United States hospitals lack negative pressure, health care worker, and medical equipment/supplies surge capacity. Hospitals must continue to address gaps in infectious disease emergency planning. PMID- 17276789 TI - Novel use of the intranet to document health care personnel participation in a mandatory influenza vaccination reporting program. AB - BACKGROUND: The Advisory Committee on Immunization Practices and the Healthcare Infection Control Practices Advisory Committee recommend health care personnel (HCP) influenza vaccination to prevent transmission to patients. Recommendations include documenting declination and providing feedback of rates. We report the use of the intranet to achieve recommendations with mandatory participation of 20,170 HCP in an 1100-bed hospital. METHODS: Employees were required to log onto the intranet and select "vaccine received," "contraindicated," or "declined." Declining employees automatically received a screen with education about vaccination. A Microsoft Structured Query Language database was created and linked to a Human Resource database. Administrators were provided feedback on participation rates. Employees were notified of the program via letter. Reminders were provided through managers and newsletters. RESULTS: Eighty-nine percent (17,998/20,170) accessed the intranet. Fifty-five percent (11,068) indicated "vaccine received" versus 38% in 2004-2005 (P < .000001), 31% (6300) "declined," and 3% (630) had "contraindications." Unit rates ranged from 24% to 91%. CONCLUSION: The intranet provides a tool for measuring and reporting participation, declination, and vaccination rates. The intranet and a mandatory participation program were associated with an increase in rates. Low rates in HCP with access to, and education about, vaccine may impact consideration of a mandatory vaccination program. PMID- 17276790 TI - Perceptions related to human avian influenza and their associations with anticipated psychological and behavioral responses at the onset of outbreak in the Hong Kong Chinese general population. AB - BACKGROUND: Anticipated psychological responses and perceptions of risk have not been examined prior to the outbreak of an epidemic. METHODS: Using a cross sectional, telephone survey, 805 Chinese adults in Hong Kong were interviewed anonymously in November, 2005 to examine beliefs related to H5N1 avian influenza and anticipated responses. RESULTS: Of respondents, 71.4% and 52.4%, respectively, believed that bird-to-human or human-to-human H5N1 transmission would occur in the next year. In the event of a bird-to-human or human-to-human outbreak in Hong Kong, many anticipated high fatality rates (70.5% and 74.4%, respectively), permanent physical damage (52.0% and 54.9%, respectively), inadequate vaccines (50.0% and 64.4%, respectively), insufficient medicine supplies (43.7% and 54.5%, respectively), inadequate hospital infection control (35.1% and 43.3%, respectively), high susceptibility of family members contracting H5N1 (13.9% and 24.3%, respectively), and impact on oneself/family worse than those of severe acute respiratory syndrome (21.2 and 25.0%, respectively). Most anticipated at least 1 of the 7 studied stress-related responses (e.g., panic) or the adoption of at least 1 of the 5 studied preventive behavioral measures (e.g., avoiding going out). CONCLUSION: Panic and interruption of daily routines may occur in the event of a human avian influenza outbreak. Dissemination of accurate, timely information would reduce unnecessary distress and unwanted behaviors. PMID- 17276791 TI - How to provide an effective primary health care in fighting against severe acute respiratory syndrome: the experiences of two cities. AB - OBJECTIVES: This study was designed to compare the response and management of severe acute respiratory syndrome (SARS) by the family physicians of the Hong Kong and the Toronto health systems, and to provide evidence to improve health policy and practices in a newly emerging infectious disease. METHODS: A questionnaire was sent to family medicine tutors affiliated with either the Chinese University of Hong Kong or the University of Toronto in 2003. The survey questions covered training for SARS, the use of screening tools, an anxiety scale, clinical practices, and demographic data. RESULTS: 137 (74.8%) and 51 (34%) doctors from Hong Kong and Toronto replied to the questionnaire, respectively. Most (80-84.6%) had no training in infectious disease control and were not confident in dealing with SARS (68.1-73.5%). In Hong Kong, the screening tools provided by international agencies did not meet the local needs. In Toronto, lack of a centralized hospital admission policy and fully public laboratory probably resulted in appointment cancellation and dissatisfaction. There may be a need for deployment of personnel between institutions but loss of income was not a major concern. CONCLUSIONS: Sharing the "lessons learned" in different regions during a SARS outbreak will help prepare for the next epidemic. PMID- 17276792 TI - Attitudes of health care workers to influenza vaccination: why are they not vaccinated? AB - BACKGROUND: Compliance rates with influenza vaccination among health care workers (HCW) are historically low. Although a safe and effective vaccine is available, the reasons for such poor compliance are not well understood. METHODS: After a campaign encouraging HWC to vaccinate against influenza, we conducted an epidemiologic survey to evaluate the reasons for compliance and accompanied the impact of these measures (campaign and questionnaire) during the subsequent 2 years. RESULTS: Compliance rate was 34.4%. Multivariate analysis showed that "older age" (P = .008), "believing that most departmental colleagues had been vaccinated" (P < .0001), and "having cared for patients suffering from severe influenza" (P = .031) were significantly associated with compliance with influenza vaccination. The main reason given for being vaccinated was "individual protection" and, to a lesser extent, "protection for the patient." In subsequent years, compliance rates among those participating in the survey fell to 20.2% in 2004, when the only measure taken was the questionnaire, and to 12.75% in 2005, when no educational intervention was scheduled. CONCLUSION: We conclude that a better understanding of HCW's negative attitude regarding influenza vaccination is needed as are more appealing and convincing continuous education programs, to ensure motivation for influenza vaccination over a longer period. PMID- 17276793 TI - An analysis of the current status of hospital emergency preparedness for infectious disease outbreaks in Beijing, China. AB - BACKGROUND: In the event of a large-scale infectious disease outbreak, hospitals will play a critical role. The objective of our study is to understand the current status of hospitals preparedness for infectious disease outbreaks in Beijing and to provide basic information for infectious disease prevention and control in hospitals. METHODS: One hundred fifty-two secondary and tertiary care hospitals in Beijing were surveyed by a standardized questionnaire. Data related to hospital demographic information and their emergency plans, laboratory diagnosis capacity, medical treatment procedures for infectious diseases, stockpiles of drugs and personal protective equipment, and staff training were collected. RESULTS: Responses were received from 134 (88.2%) of the 152 hospitals surveyed. Overall, hospitals reported that the number of physicians and nurses in infectious disease accounted for only 1.8% of the total physicians and 2.5% of the total nurses, and surgery beds accounted for 8.5% of all the fixed beds. Approximately 93.3% of the hospitals surveyed reported that they had an emergency plan, and none of those reported that their laboratories were able to isolate and identify all 8 kinds of common pathogens of infectious diseases: 22.4% of the hospitals had medical treatment procedures for all these infectious diseases, 23.1% had stored specific drugs for treatment, 2.2% had all personal protective equipment, and 30.6% reported that their health care staff had been trained in hospital emergency preparedness for infectious diseases. In general, emergency preparedness for infectious diseases in tertiary care hospitals was better than that in secondary care hospitals; the preparedness at general hospitals was better than that at specialized hospitals; and that at teaching hospitals was better than that at nonteaching hospitals. CONCLUSION: Emergency preparedness for infectious disease at hospitals in Beijing was in an early stage of development during this survey. Comprehensive measures should be developed and implemented to enhance their capacity for infectious disease emergency. PMID- 17276794 TI - Frequent stepping on and off the footstool contaminates the operative field. PMID- 17276795 TI - Recurrent infections caused by Pseudomonas aeruginosa strains in a unique patient. PMID- 17276796 TI - Can avian bird flu virus pass through the eggshell? An appraisal and implications for infection control. PMID- 17276798 TI - KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. PMID- 17276799 TI - Corpora amylacea in a leiomyoma of soft tissue. AB - A case of myxoid leiomyoma of deep soft tissue is described. The patient was a 42 year-old woman who presented with menorrhagia, and an ischiorectal mass was identified. A total hysterectomy was performed, and the mass was removed. On gross examination, the mass was 6cm x 5cm x 4cm and had a mucoid cut surface. Histologic examination revealed a myxoid leiomyoma with abundant intracellular corpora amylacea (CA). An infarcted leiomyoma was present in the hysterectomy specimen. The patient remains well, with no evidence of recurrence 3 years after surgery. Leiomyomas of deep soft tissue are rare, and, to our knowledge, none have been described containing CA. PMID- 17276800 TI - A depression screen and intervention for older ED patients. AB - The objectives of this study were to determine the effect of screening examinations for depression on the care of older emergency department (ED) patients and to assess recognition of depression by emergency physicians (EPs). This was a prospective interventional study of 267 patients 70 years or older. Patients were screened for depression using the Short-Form Geriatric Depression Scale, and the results were presented to EPs after assessing EP recognition of depression. The prevalence of depression was 16.5% (44/267; 95% confidence interval, 12.0%-20.9%). Fifteen (34.1%) of 44 patients with depression were recognized by EPs as being depressed. Screening results did not alter care in any of the 44 patients with depression. No patients were given referrals or discharge instructions specifically to address depression. Depression is highly prevalent and poorly recognized in older ED patients. Use of the Short-Form Geriatric Depression Scale did not alter care of older patients with depression. PMID- 17276801 TI - Can elevated troponin I levels predict complicated clinical course and inhospital mortality in patients with acute pulmonary embolism? AB - OBJECTIVE: The purpose of this study was to evaluate the value of elevated cardiac troponin I (cTnI) for prediction of complicated clinical course and in hospital mortality in patients with confirmed acute pulmonary embolism (PE). METHODS AND RESULTS: This study was a retrospective chart review of patients diagnosed as having PE, in whom cTnI testing was obtained at emergency department (ED) presentation between January 2002 and April 2006. Clinical characteristics; echocardiographic right ventricular dysfunction; inhospital mortality; and adverse clinical events including need for inotropic support, mechanical ventilation, and thrombolysis were compared in patients with elevated cTnI levels vs patients with normal cTnI levels. One hundred sixteen patients with PE were identified, and 77 of them (66%) were included in the study. Thirty-three patients (42%) had elevated cTnI levels. Elevated cTnI levels were associated with inhospital mortality (P = .02), complicated clinical course (P < .001), and right ventricular dysfunction (P < .001). In patients with elevated cTnI levels, inhospital mortality (odds ratio [OR], 3.31; 95% confidence interval [CI], 1.82 9.29), hypotension (OR, 7.37; 95% CI, 2.31-23.28), thrombolysis (OR, 5.71; 95% CI, 1.63-19.92), need for mechanical ventilation (OR, 5.00; 95% CI, 1.42-17.57), and need for inotropic support (OR, 3.02; 95% CI, 1.03-8.85) were more prevalent. The patients with elevated cTnI levels had more serious vital parameters (systolic blood pressure, pulse, and oxygen saturation) at ED presentation. CONCLUSION: Our results indicate that elevated cTnI levels are associated with higher risk for inhospital mortality and complicated clinical course. Troponin I may play an important role for the risk assessment of patients with PE. The idea that an elevation in cTnI levels is a valuable parameter for the risk stratification of patients with PE needs to be examined in larger prospective studies. PMID- 17276802 TI - Specialized emergency nurses treating ankle and foot injuries: a randomized controlled trial. AB - OBJECTIVE: To cope with emergency departments (EDs) being progressively overcrowded, the concept of specialized emergency nurses (SENs) was conceived. In this study, the ability of SENs to treat ankle/foot injuries was assessed. METHODS: Regular emergency nurses were trained in a 2-day session that addressed all aspects of ankle/foot injuries. A randomized controlled trial was set up in which the diagnostic accuracy of SENs was compared with that of house officers (HOs). Secondary outcome parameter was patient satisfaction measured by a standardized questionnaire. RESULTS: In total, 512 consecutive patients were included. The sensitivity of SENs was 0.94 (95% confidence interval [CI], 0.78 0.99) compared with 0.78 (95% CI, 0.57-0.91) of HOs. Specificity was 0.94 (95% CI, 0.90-0.97) for SENs compared with 0.95 (95% CI, 0.91-0.98) for HOs. The delivered care by SENs was found to be significantly better and the median waiting time at the ED was significantly reduced (21 minutes for SENs vs 32 minutes for HOs). CONCLUSIONS: Specialized emergency nurses are capable of assessing and treating ankle/foot injuries accurately with excellent patient satisfaction and with a reduction of waiting times. Other injury-specific courses are now developed for this approach. PMID- 17276804 TI - Helicopter emergency medical services and stroke care regionalization: measuring performance in a maturing system. AB - This study retrospectively analyzed 123 patients undergoing helicopter emergency medical services transport for ischemic stroke (ischemic cerebrovascular accident) to the Massachusetts General Hospital during 2000-2004. To assess for system improvements over time, data were analyzed between the 2 consecutive 30 month periods comprising the 5-year study. Patients transported during the latter 30 months were transported from lesser distances (P = .002), were more likely to be younger than 65 years (P = .005), and were more likely to have documented symptom onset time (P = .03) and National Institutes of Health Stroke Scale (odds ratio, 3.6; 95% confidence interval, 1.7-7.6; P = .001). Time end points analysis found no significant improvements in any intervals compared across the 2 study eras. Age older than 65 years was the only covariate associated with a more rapid arrival at the Massachusetts General Hospital (odds ratio, 2.4; 95% CI, 1.1-5.4; P = .03). This study of our stroke transport system identified both areas of good performance and also areas for focusing further improvement efforts. PMID- 17276803 TI - Clinical prediction rule to distinguish pelvic inflammatory disease from acute appendicitis in women of childbearing age. AB - OBJECTIVE: We aimed to develop a clinical prediction rule to distinguish pelvic inflammatory disease (PID) from acute appendicitis in women of childbearing age. METHODS: We reviewed medical records over a 4-year period of female patients of childbearing age who had presented with abdominal pain at an urban emergency department and had either appendicitis (n = 109) or PID (n = 72). A prediction rule was developed by use of recursive partitioning based on significant factors for the discrimination. RESULTS: The significant factors to favor PID over appendicitis were (1) no migration of pain (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.5-11.5), (2) bilateral abdominal tenderness (OR, 16.7; 95% CI, 5.3-50.0), and (3) absence of nausea and vomiting (OR, 8.4; 95% CI, 2.8-24.8). The prediction rule could rule out appendicitis from PID with sensitivity of 99% (95% CI, 94-100%) when classified as a low-risk group by the following factors: (1) no migration of pain, (2) bilateral abdominal tenderness, and (3) no nausea and vomiting. CONCLUSION: We developed a prediction rule for childbearing-aged women presenting with acute abdominal pain to distinguish acute appendicitis from PID based on 3 simple, clinical features: migration of pain, bilateral abdominal tenderness, and nausea and vomiting. Prospective validation is needed in other settings. PMID- 17276805 TI - ED presentations of acute renal infarction. AB - OBJECTIVE: The objective of the study was to investigate initial clinical characteristics that can suggest an early diagnosis of patients with acute renal infarction presenting with flank and/or abdominal pain in the emergency department (ED). METHODS: From January 1, 1996, through December 31, 2005, 20 adult patients with renal infarction diagnosed by contrast-enhanced computed tomography in the ED were enrolled. Medical records, including demographic data, risk factors for thromboembolism, initial clinical presentations, laboratory data, treatment programs and outcomes, were retrospectively reviewed and analyzed. RESULTS: Mean patient age was 60.3 years (range, 21-80). The estimated incidence of renal infarction was 0.004% (20 of 481,540) among the ED census. The median time of onset of symptoms before the ED visit was 31 hours (range, 1-285). Eighteen patients (90%) had a history of more than 1 risk factor for thromboembolic events. In clinical presentations, all the patients had either abdominal or flank pain and tenderness. Nineteen patients (95%) had an elevated serum lactate dehydrogenase level with a mean +/- SD of 812.1 +/- 569.4 U/L. Sixteen patients (80%) presented with the triad--persisting flank or abdominal pain/tenderness, elevated serum lactate dehydrogenase level, and proteinuria. Among all 20 patients, 10 patients (50%) were diagnosed as having renal infarction at the initial ED visit. No specific clinical characteristics could be identified to distinguish those patients diagnosed early and those with delayed diagnosis. All 20 patients received medical treatment with coumadin, which was given in combination with heparin treatment in 11, peripheral intravenous and/or local intra-arterial thrombolytics with urokinase in 5, and mitral valve replacement in 1. No patient died. Although 4 patients had a mildly elevated serum creatinine level (>1.5 mg/dL) during hospitalization, none of them needs dialysis after more than 1 year of follow-up. CONCLUSIONS: In this study, we delineated specifically clinical features for emergency physicians to raise their suspicion index for an early diagnosis of patients with renal infarction, a disease which is uncommon and is usually delayed or missed at initial ED presentation. PMID- 17276806 TI - Electrocardiographic features and prognosis in acute diagonal or marginal branch occlusion. AB - The aim of our study was to analyze electrocadiographic changes in patients with acute myocardial infarction related to the occlusion of diagonal (DG) or marginal (MG) branch. We selected 13 cases with DG and 12 with MG occlusion on angiography and evaluated their electrocardiogram (ECG) patterns on admission obtained in emergency department (ED) of university hospital with catheterization laboratory serving everyday interventional cardiology duty for ACS. Most characteristic ECG changes in acute occlusion of DG observed in 12 patients (92.3%) included ST segment elevation in leads V(2) and V(3) (mean, 1.2 +/- 0.5 mm; maximum, 1.7 mm) and ST-segment depression in leads II and III (mean, 0.9 +/- 0.4 mm; maximum, 1.5 mm). Most characteristic ECG changes for acute occlusion of MG were ST-segment depression in leads V(5) and V(6) (mean, 0.9 +/- 0.4 mm; maximal, 1 mm) observed in 11 (91.7%) patients, ST-segment depression in lead II (mean, 0.7 +/- 0.2 mm; maximal, 0.8 mm) in 10 (83.3%,) and in leads V(2) and V(3), and aVF in 8 (66.7%) of cases. Risk of complications including cardiogenic shock and death was high in both groups especially during acute phase of myocardial infarction. Prevalence of borderline ECG changes in patients with acute coronary occlusion confirms how important is precise ECG interpretation usually initially done by ED physician. PMID- 17276807 TI - Electrocardiographic artifacts due to electrode misplacement and their frequency in different clinical settings. AB - Misplacement of electrodes can change the morphology of an electrocardiogram (ECG) in clinical important ways. To assess the frequency of these errors in different clinical settings, we collected ECGs routinely performed at the cardiology outpatient clinic and the intensive care unit. Lead misplacement was suspected when one of the following morphological changes occurred: QRS axis between 180 degrees and -90 degrees , positive P wave in lead aVR, negative P waves in lead I and/or II, very low (<0.1 mV) amplitude in an isolated peripheral lead, or abnormal R progression in the precordial leads. We analyzed 838 ECGs and identified 37 ECGs suspicious for electrode misplacement, from which 7 were confirmed. The frequency of ECG artifacts due to switched electrodes was 0.4% (3/739) at the outpatient clinic and 4.0% (4/99) at the intensive care unit (P = .005). In conclusion, errors in ECG performance do occur with an increasing frequency in an acute medical care setting. PMID- 17276808 TI - Accuracy of the cerebrospinal fluid results to differentiate bacterial from non bacterial meningitis, in case of negative gram-stained smear. AB - OBJECTIVE: The aim of this study was to evaluate the usefulness of various laboratory results for differential diagnosis of bacterial (BM) and nonbacterial meningitis (NBM) with negative initial Gram stain. DESIGN AND SETTING: A prospective multicenter study was conducted in the emergency departments of 3 teaching hospitals. PARTICIPANTS AND METHODS: Consecutive adult patients with a diagnosis of meningitis based on compatible clinical features and cerebrospinal fluid (CSF) culture findings with a CSF leukocyte count greater than 5/mm(3) were included in the study. Symptoms, examination findings, data from laboratory results, including CSF results and serum C-reactive protein (CRP) levels, and clinical outcome were assessed. RESULTS: One hundred fifty-one patients (age, 35 +/- 15 years) with confirmed meningitis were admitted: 133 with NBM and 18 with BM. CRP and procalcitonin (PCT) levels, CSF white cell and absolute neutrophil counts, and CSF glucose/blood glucose and CSF protein levels were significantly higher in the BM group. However, as diagnostic indicators of BM, none of these variables except PCT was more efficient than that of the emergency physician. Values of the area under the receiver operating characteristic curve were 0.59 (95% confidence interval [CI], 0.21-0.82), 0.79 (95% CI, 0.47-0.92), 0.18 (95% CI, 0.0-0.43), 0.70 (95%CI, 0.30-0.89), 0.81 (95% CI, 0.58-0.92), and 0.98 (95% CI, 0.83-1.0) for CSF leukocyte count, percentage of CSF leukocyte, CSF/blood glucose ratio, CSF protein level, serum CRP, and serum PCT (P < .05 vs CRP), respectively. CONCLUSION: CSF results have a modest role in distinguishing BM from NBM in a negative Gram stain for bacteria. PCT serum levels seem to be an excellent predictor of BM. PMID- 17276810 TI - Right upper lobe pulmonary edema as consequence of mitral regurgitation. PMID- 17276809 TI - Health care facilities' "war on terrorism": a deliberate process for recommending personal protective equipment. AB - The protection of health care facility (HCF) staff from the effects of weapons of mass destruction has gained heightened attention since the 9-11 terrorist attacks. One critical component of protection is personal protective equipment (PPE). No universal standard exists for an "essential" level of PPE for HCF staff. The absence of such a standard raises the need for development of national policy for PPE levels, particularly in HCFs. We describe a process used by the Veterans Health Administration for recommending policy for "essential" PPE levels. Although the recommendations are specific for Veterans Health Administration, the process, findings, and applications may be useful to other institutions as they attempt to resolve this critical issue. This descriptive account will serve to generate practical scientific debate in the academic community and lead to definitive public policy recommendations for the Nation's HCFs in executing their roles in the event of a terrorist attack. PMID- 17276812 TI - Unrecognized periorbital penetrating nail in the brain: case report. PMID- 17276811 TI - Delayed clinical decompensation and death after pediatric nifedipine overdose. PMID- 17276813 TI - A vaccine misadventure. PMID- 17276814 TI - The "forbidden" chest x-ray: tension pyopneumothorax. PMID- 17276815 TI - All stressed out and no pump to go. PMID- 17276816 TI - Feeling bloated. PMID- 17276817 TI - Transorbital ventricular decompression in an acutely decompensated hydrocephalic ED patient. PMID- 17276818 TI - Acute heart failure associated with venlafaxine poisoning. PMID- 17276819 TI - Detection of a giant wooden foreign body with multidetector computed tomography and multiplanar reconstruction imaging. AB - We describe the case of an unusual (unbelievable) giant wooden foreign body traversing the neck via the glabella. The relationship between the giant wooden foreign body and the nasopharynx air column was demonstrated through multidetector computed tomography (CT). The wooden foreign body mimicking air on a standard CT window setting was distinguished from air with the use of a higher CT window setting. Cases of accidental penetration injury of the head and neck by foreign bodies are not rare, but the entry of giant wooden foreign bodies into the neck via the glabella has never been reported in the literature. In our case patient, such a giant wooden foreign body was detected neither in the emergency department nor during radiologic investigations (conventional radiograms and standard CT) until the patient underwent multidetector CT 8 days after the related accident. PMID- 17276820 TI - Inability to pass a nasogastric tube: a surgical emergency. PMID- 17276821 TI - Anticholinergic toxicity associated with the ingestion of lupini beans. PMID- 17276822 TI - Fat embolism syndrome with multiple hypointensity signals detected by head magnetic resonance imaging demonstrating a favorable outcome: a case report. PMID- 17276823 TI - Isolated headache as the sole manifestation of dural sinus thrombosis: a case report with literature review. PMID- 17276824 TI - Tension viscerothorax mimicking tension pneumothorax. PMID- 17276825 TI - Ectopic pregnancy presenting as rectal pain. PMID- 17276826 TI - Nursemaid's elbow in a 31-year-old female. PMID- 17276827 TI - Disseminated head and neck emphysema with pneumocephalus due to air compressor injury into orbit. PMID- 17276828 TI - Fulminant fatal toxic shock syndrome with Staphylococcus aureus. PMID- 17276829 TI - Massive hiatal hernia masquerading as a tension pneumothorax. PMID- 17276830 TI - Retrobulbar hemorrhage resulting from syncopal seizures after a dental procedure. PMID- 17276831 TI - Takotsubo cardiomyopathy associated with sepsis in type 2 diabetes mellitus. PMID- 17276832 TI - Uncommon cardiovascular manifestations after a Latrodectus bite. PMID- 17276833 TI - Inverted U wave, a specific electrocardiographic sign of cardiac ischemia. PMID- 17276834 TI - Misleadingly migratory pain in acute renal infarction. PMID- 17276835 TI - Recurrent hyponatremia under desmopressin overdosing: is abuse a possible explication? PMID- 17276836 TI - An irreducible posterior knee dislocation. PMID- 17276837 TI - Axillary artery dissection due to blunt shoulder trauma. PMID- 17276838 TI - Stress-induced cardiomyopathy: takotsubo left ventricular dysfunction. PMID- 17276839 TI - Pneumocephalus secondary to an epidural blood patch. PMID- 17276840 TI - Severe headache caused by dilatative arteriopathy of the internal carotid artery. PMID- 17276841 TI - Spontaneous splenic rupture secondary to pegfilgrastim to prevent neutropenia in a patient with non-small-cell lung carcinoma. PMID- 17276842 TI - Acute myocardial infarction in the setting of an apparent pacemaker anomaly: ventricular pseudofusion. PMID- 17276843 TI - Spontaneous subarachnoid hemorrhage after intravenous epinephrine use for multiple bee stings. PMID- 17276844 TI - Severe explosive headache: a sole presentation of acute myocardial infarction in a young man. PMID- 17276845 TI - Complete common iliac artery transection: an easily misdiagnosed but fatal complication of blunt abdominal injury. PMID- 17276846 TI - Cardiac rescue with intra-aortic balloon counterpulsation in refractory shock due to acute meningococcemia. PMID- 17276848 TI - The effect of the gravitation of the moon on acute myocardial infarction. PMID- 17276847 TI - Proper observation of patient-related factors is an important determinant in the use of the D-dimer test for exclusion of venous thromboembolism in the ED. PMID- 17276849 TI - Internet-based survey on the use of additional lead electrocardiograms and fibrinolysis of posterior and right ventricular acute myocardial infarctions. PMID- 17276851 TI - The case for treatment guidelines. PMID- 17276852 TI - Rapid orthodontic tooth movement aided by alveolar surgery in beagles. AB - INTRODUCTION: It has been reported that oral surgery can accelerate orthodontic tooth movement. The purpose of this study was to evaluate the effects of alveolar surgery that undermines interseptal bone in orthodontic tooth movement. METHODS: Ten male beagles, aged 12 to 15 months, were used in this study. Extraction of the mandibular second premolar and alveolar surgery to reduce the osteal resistance on the mesial side of the extraction socket were performed on the experimental side; on the control side, only the second premolar was extracted. The first premolars were distalized against the third premolars with orthodontic nickel-titanium coil springs on the both sides. The beagles were killed in the first, second, third, fourth, and eighth weeks after orthodontic force application. RESULTS: The first premolar on the experimental side moved more rapidly than that on the control side (P <.01). Tissue slices were obtained for histological evaluation. No obvious root resorption and no irreversible injury to the pulp were observed on either side. Active and extensive bone resorption in the compressive area and bone deposition in the tension area were observed on the experimental sides. CONCLUSIONS: Self-fluorescence checks showed that more new bone was deposited in the tension area of the experimental side than on the control side (P <.05). These results suggest that alveolar surgery might be an effective and safe way to aid orthodontic tooth movement. PMID- 17276853 TI - Xeno III self-etching adhesive in orthodontic bonding: the next generation. AB - INTRODUCTION: The newer single-step self-etching adhesives that etch, prime, and apply the resin bonding agent simultaneously without rinsing have been increasing in popularity in orthodontic bonding. The purpose of this study was to compare the bond strengths and to evaluate the debonding site (with the adhesive remnant index), when a conventional acid-etch conditioner and a self-etching adhesive system (Xeno III, Dentsply DeTrey GmbH, Konstanz, Germany) were used with either a composite resin adhesive (Transbond XT, 3M Unitek, Monrovia, Calif) or a resin modified glass ionomer cement (Fuji Ortho LC, GC Corp, Tokyo, Japan). METHODS: One hundred twenty extracted human premolars were mounted in acrylic resin and randomly assigned to 6 groups of 20 teeth each. Shear-peel bond strength testing was performed after thermocycling (5 degrees C-55 degrees C for 500 times) with a Zwick 1440 compression machine (Zwick, Ulm, Germany). RESULTS: The results showed that the bond strengths achieved with Xeno III were comparable with the traditional methods of either 37% phosphoric acid or 10% polyacrylic acid for both Transbond XT and Fuji Ortho LC. Adhesive remnant index scores showed less adhesive remaining on the tooth surface in the Xeno III/Transbond XT adhesive only (no primer) group. CONCLUSIONS: Xeno III can be used to bond orthodontic brackets with the adhesives in this study. PMID- 17276854 TI - Applicability of mathematical curve-fitting procedures to late mixed dentition patients with crowding: a clinical-experimental evaluation. AB - INTRODUCTION: This study aimed at investigating the applicability of a polynomial function laterally, combined with a parabola or hyperbolic cosine function in the front, for mandibular curve-fitting purposes in late mixed dentition patients with crowding. The possible advantages of using a bilateral center of gravity for curve construction were examined. METHODS: After digitizing 30 mandibular casts (14 boys, 16 girls), 14 coordinates per model were used to fit a hyperbolic cosine function or a parabola in the anterior segment and a third-degree polynomial function bilaterally, by using the method of least squares. The lateral functions were fitted by using a mirrored center of gravity for the premolar/molar area. To assess curve fit and enable comparison with other studies, Pearson correlation coefficients, residuals, mean square error, root mean square values, and average perpendicular distance of the points to the constructed curve were calculated. RESULTS AND CONCLUSIONS: High correlation coefficients were found (mean, 0.994; SD, 0.004). The mean square error (1.80 mm2, SD, 1.12 mm2) and the average root mean square value (1.28 mm, SD, 0.42 mm) appears to be comparable with other studies. Combined with the relatively low average perpendicular distance of the points to the curve (mean, 0.47 mm; SD, 0.16 mm), it seems that this method is successful in describing mandibular arch forms of mixed dentition patients with crowding, and it could be a useful tool in treatment planning. PMID- 17276855 TI - Comparison of 2 distalization systems supported by intraosseous screws. AB - INTRODUCTION: The aim of this study was to compare the effects of 2 distalization systems supported by intraosseous screws for maxillary molar distalization. METHODS: Forty subjects with skeletal Class I dental Class II malocclusion were divided into group 1 (8 girls, 12 boys) and group 2 (11 girls, 9 boys). An anchorage unit was prepared by placing an intraosseous screw in the premaxillary area of each subject. To increase the anchorage in group 2, we used an acrylic plate resembling the Nance button around the screw. The screws were placed and immediately loaded to distalize the maxillary first molars or second molars when they were present. Skeletal and dental changes were measured on cephalograms, and dental casts were obtained before and after distalization. RESULTS: The average distalization times were 4.6 months for group 1 and 5.4 months for group 2. On the cephalograms, the maxillary first molars were tipped 9.05 degrees in group 1 and 0.75 degrees in group 2. The mean distal movements were 3.95 mm in group 1 and 3.88 mm in group 2. On the dental casts, the mean distalization amounts were 4.85 mm for group 1 and 3.70 mm for group 2. In group 1, the maxillary molars were rotated distopalatally to a moderate degree, but this was not significant in group 2. Mild protrusion of the maxillary central incisors was also recorded for group 1 but not for group 2. However, there were no changes in overjet, overbite, and mandibular plane angle measurements for either group. CONCLUSIONS: Immediately loaded intraosseous screw-supported anchorage units were successful for molar distalization in both groups. In group 2, side effects such as molar tipping and rotation were smaller, but distalization times were longer and hygiene was poorer. PMID- 17276856 TI - Dental health assessed more than 10 years after interproximal enamel reduction of mandibular anterior teeth. AB - INTRODUCTION: We investigated whether interdental enamel reduction using fine diamond disks with air cooling, followed by polishing, leads to iatrogenic damage or reduced interradicular distances. METHODS: Our subjects were 61 consecutive patients who had received mesiodistal enamel reduction of all 6 mandibular anterior teeth more than 10 years previously. Dental caries, bleeding on probing, probing depths, and gingival recessions were assessed with standard techniques. Incisor irregularities and tooth width/thickness ratios were measured on models, and the patients were asked about any increased tooth sensitivity. The reference group comprised 16 students. RESULTS: No new caries lesions were detected. Three mature adults had some minor labial gingival recessions. There was no evidence of root pathology. The distance between the roots of the mandibular incisors was statistically significantly greater in the patients who had received stripping than in those who had not; 59 of 61 patients reported no increased sensitivity to temperature variations. The overall irregularity index at follow-up was only 0.67 (SD, 0.64). CONCLUSIONS: Interdental enamel reduction according to this protocol did not result in iatrogenic damage. Dental caries, gingival problems, or alveolar bone loss did not increase, and the distances between the roots of the teeth in the mandibular anterior region were not reduced. The overall incisor irregularity at the follow-up examination was small. PMID- 17276857 TI - Patients' perceptions of recovery after routine extraction of healthy premolars. AB - INTRODUCTION: In this prospective study, we evaluated patients' perceptions of recovery after orthodontic premolar extractions. METHODS: Thirty patients (18 girls, 12 boys, mean age 14.6 +/- 3.8 years) were given a health-related quality of life questionnaire to be completed each postoperative day (POD) for 7 days. The questionnaire was designed to assess each patient's perception of recovery: pain, oral function, general activity measures, and other variables. The impact of possible predictor variables, such as age, sex, length of surgical procedure, number of simultaneous extractions, and time during the day, was assessed. RESULTS: Severe pain (16.7%, 3.3%) and consumption of analgesics (70%, 13.2%) declined dramatically from POD 1 to POD 2. Improvements in oral function and other symptoms were evident by POD 2. Absence from school resembled interference in daily activities (POD 2). Age was the most significant predictor variable, with results showing delayed recoveries for patients older than 15 years. The most striking differences were reported for enjoying food (P <.05), taste (P <.05), and food stagnation (P <.05). The number of extractions performed at the same appointment had no affect on posttreatment recovery. CONCLUSIONS: This study was designed to provide baseline health-related quality of life information with which to compare other surgical procedures frequently needed in orthodontic treatment, such as removal of third molars and exposure of impacted teeth. Additionally, it provides information for patients and clinicians on postoperative recovery after premolar orthodontic extractions. PMID- 17276859 TI - Treatment effects of the bionator and high-pull facebow combination followed by fixed appliances in patients with increased vertical dimensions. AB - INTRODUCTION: The purpose of this study was to evaluate the effectiveness of a first phase of bionator and high-pull facebow treatment followed by a second phase of fixed appliance therapy in growing subjects with increased vertical dimensions. METHODS: The records of 24 subjects with high-angle skeletal relationships (mean MPA value approximately 30 degrees) treated consecutively with this protocol were examined. Cephalometric measurements were compared with those obtained from 23 sets of records of an untreated group matched according to age, gender, vertical skeletal relationships, and time intervals between records. The matched group of patients was from the University of Michigan Elementary and Secondary School Growth Study. Lateral cephalograms were analyzed prior to the start of treatment (T1, mean age 9.1 years), at the start of phase 2 treatment (T2, mean age 11.9 years), and after phase 2 treatment (T3, mean age 14.7 years). The total treatment duration (phase 1, retention, and phase 2) for the treated group was 5.5 years, whereas the control group total time interval averaged 5.6 years. RESULTS: As to sagittal relationships, no significant differences were found between treated subjects and controls at the end of the 2-phase treatment for all measurements. Counterintuitively, the bionator and high-pull headgear combination worsened the hyperdivergent facial pattern at a clinically significant level, as shown by analysis of final facial forms. The treated group exhibited a significantly larger MPA value than controls (2.5 degrees) as well as a larger inclination of the Frankfort horizontal to the occlusal plane (2.8 degrees ). CONCLUSIONS: Based on the analysis of this sample, the examined therapeutic protocol does not appear to be a recommendable option for treatment of subjects with increased vertical dimensions. PMID- 17276858 TI - The effects of oral appliance therapy on occlusal function in patients with obstructive sleep apnea: a short-term prospective study. AB - INTRODUCTION: The aim of this study was to objectively and prospectively assess whether oral appliances (OAs) alter occlusal function in patients treated for snoring or obstructive sleep apnea. METHODS: The occlusal contact area (OCA) and bite force (Bf) of 12 patients who used OAs were measured with pressure-sensitive sheets in the morning and evening with the Dental Prescale Occluzer System. OCA and Bf were compared in each measurement period by using ANOVA. Percentage changes in the morning relative to the evening (OCA(M-E) and Bf(M-E)) were compared between the 2 periods by using the Wilcoxon signed rank test. Correlations between percentage changes in pretreatment and posttitration ((Pre Post)OCA and (Pre-Post)Bf), age, and cephalometric variables were also assessed. RESULTS: Patients showed significant decreases in OCA and Bf when posttitration readings were compared with corresponding pretreatment measurements. OCA(M-E) and Bf(M-E) were significantly different between pretreatment and posttitration, suggesting that OCA and Bf tend to be smaller in the morning with OA use. (Pre Post)Bf measured in the evening correlated with age. CONCLUSIONS: Effects on occlusal function after OA use were observed. These results suggest that practitioners should pay attention to the possible side effects of OAs on the dentition when treating patients with snoring or obstructive sleep apnea. PMID- 17276860 TI - Kinesiographic and sonographic changes in young Class II patients treated with functional appliances. AB - INTRODUCTION: The aim of this prospective, longitudinal, case-series study was to analyze the effect of orthodontic treatment by means of an activator appliance on the temporomandibular joint disc-condyle complex. METHODS: The sample included 27 consecutively treated subjects with Class II Division 1 malocclussions (21 boys, 6 girls) who underwent orthodontic therapy with activators. The average pretreatment age was 11 years 2 months. Before treatment, all subjects were free of signs and clinical symptoms of temporomandibular joint disorders. The average treatment time with the activator appliance was 366 days; then all patients had Class I dental relationships. Kinesiographic and sonographic records before and after orthodontic treatment with the activator appliance were used to evaluate the disc-condyle complex. Univariate statistics were used in these outcome measurements to evaluate differences before and after treatment. RESULTS: After treatment, the maximum opening increased significantly (4.81 mm), but the lateral and protrusive excursions did not change. The sonographic study showed no differences in temporomandibular joint sounds before and after treatment. CONCLUSIONS: These results suggest that orthodontic treatment with an activator in a child without signs and clinical symptoms of temporomandibular joint disorders before treatment is not a risk factor for the development of temporomandibular pathology or mandibular dysfunction. PMID- 17276861 TI - Evaluation of the treatment changes of functional posterior crossbite in the mixed dentition. AB - INTRODUCTION: Functional posterior crossbite (FPXB) malocclusion is frequently seen in the deciduous or mixed dentition. It is often accompanied by lateral mandibular shift and mandibular midline deviation because of the reduction in the width of the maxillary dental arch. The aims of this prospective study were to examine in detail the morphologic, skeletal, dental, and functional effects of FPXB, and the effects of maxillary expansion treatment with quad-helix appliance. METHODS: The experimental group consisted of 35 FPXB patients (20 girls, 15 boys) having a mean age of 10.6 +/- 1.4 years; the control group consisted of 31 normocclusive subjects (18 girls, 13 boys) with a mean age of 9.8 +/- 1.6 years. Lateral, posteroanterior, and submentovertex cephalograms, transcranial temporomandibular joint radiographs, joint vibration analysis, and electromyographic recordings were obtained from every patient before and after maxillary expansion. Magnetic resonance images were taken before treatment for diagnostic purposes. These data were collected at 1 time point in the controls. RESULTS: The pretreatment posteroanterior, submentovertex, and transcranial temporomandibular joint radiographs showed mandibular asymmetry relative to the cranial base and condylar malpositioning in the glenoid fossa. Joint vibration analysis findings showed different vibrations between the crossbite and noncrossbite sides, and imbalanced electromyographic findings in the experimental group. After treatment, the asymmetric morphology and position of the mandible and condyles were eliminated, and the stomatognathic system functions were normalized. CONCLUSIONS: Early orthodontic treatment of FPXB creates optimum conditions for normal growth of the craniofacial skeleton and normal function of the stomatognathic system. PMID- 17276862 TI - Relationship between orthodontic anomalies and masticatory function in adults. AB - INTRODUCTION: Normal mastication requires the coordinated action of many elements, including teeth, salivary glands, tongue, and masticatory muscles. Dysfunction in any of these areas can result in impaired masticatory function. Few studies dealt with the influence of occlusal conditions on the masticatory function. Our aim in this study was to examine to what extent masticatory function is impaired in subjects with occlusal anomalies. METHODS: Masticatory function was studied in 102 untreated adults. They were observed while chewing a standard test food for 20, 30, and 40 chewing strokes. Orthodontic condition was assessed with the index of complexity, outcome, and need (ICON). From the masticatory test, 3 variables were obtained: median particle size (MPS), broadness of the particle distribution (BPD), and masticatory frequency (F). RESULTS: MPS was significantly larger in subjects with ICON scores >43 (definite need subsample) than in subjects with ICON scores < or =43 (no-need subsample) when the masticatory test was performed with 20, 30, or 40 cycles (P =.05, .03, and .01, respectively). BPD also followed the same trend, but the differences were not significant (P = .33, .16, .14 for 20, 30, and 40 cycles, respectively). Also, the differences in F between the 2 subsamples were not significant (P = .26, .45, .37). CONCLUSIONS: The results suggest that, in addition to esthetic considerations, improving a patient's chewing function by improving occlusal relationships could be an indication for orthodontic treatment. PMID- 17276863 TI - Longitudinal development of caries lesions after orthodontic treatment evaluated by quantitative light-induced fluorescence. AB - INTRODUCTION: The aim of this investigation was to use quantitative light-induced fluorescence to study the natural behavior of white-spot lesions that developed in orthodontic patients during treatment with fixed orthodontic appliances, after the removal of those appliances. METHODS: The sample comprised 58 consecutively recruited patients who were at least 12 years old and who had been treated with a fixed appliance for at least 1 year in the department of orthodontics at the Academic Center for Dentistry Amsterdam, The Netherlands. They were examined with quantitative light-induced fluorescence for the presence and the extent of caries on the buccal surfaces of their teeth directly after debonding and 6 weeks and 6 months later. The fluorescence loss (DeltaF [%]) and area of lesions (mm2) were determined for all lesions found. RESULTS: A total of 421 carious lesions were recorded at debracketing with an average fluorescence loss (DeltaF(0)) of 10.3% (SD, 5.4%). During the study, 15 lesions were lost from quantitative light induced fluorescence analysis: 11 lesions (DeltaF(MAX,0) >25%) in 2 subjects were restored, and 4 were not analyzed because they were not imaged properly. Lesions varied from incipient, ie, white spot (DeltaF(0) <10%, n = 257), to advanced, ie, dentinal (DeltaF(0) >25%, n = 12). A small lesion improvement was seen 6 weeks after debracketing (P <.01), and a further lesion improvement was seen after 6 months (P <.01). Incipient lesions on average showed a smaller improvement (relative decrease, 2%; SD, 20%) than lesions with DeltaF(0) >10% (relative decrease, 12%; SD, 20%; P <.01). CONCLUSIONS: The lesions that developed during orthodontic treatment improved once the fixed appliances were removed even when they were advanced, but the overall regression was small. PMID- 17276864 TI - Thermal and mechanical characteristics of stainless steel, titanium-molybdenum, and nickel-titanium archwires. AB - INTRODUCTION: In recent years, nickel-titanium (Ni-Ti) archwires have been developed that undergo thermal transitions. Before the practitioner can fully utilize these products, the effect of those transitions within the clinical application must be understood. METHODS: The transitional temperatures and mechanical stiffnesses of 3 archwire alloys--stainless steel, beta-titanium, and Ni-Ti--were investigated were for 7 products. Among the nickel-titanium alloys, 2 were thought to represent classic Ni-Ti products and 3 copper (Cu)-Ni-Ti products. By using 2 techniques, differential scanning calorimetry to measure heat flow and dynamic mechanical analysis to measure storage modulus, transition temperatures were evaluated from -30 degrees C to +80 degrees C. RESULTS: With regard to the first technique, no transitions were observed for the stainless steel alloy, the beta-titanium alloy, and 1 of the 2 classic Ni-Ti products. For the other classic Ni-Ti product, however, a martensitic-austenitic transition was suggested on heating, and a reverse transformation was suggested on cooling. As expected, the Cu-Ni-Ti 27, 35, and 40 products manifested austenitic finish temperatures of 29.3 degrees C, 31.4 degrees C, and 37.3 degrees C, respectively, as the enthalpy increased from 2.47 to 3.18 calories per gram. With regard to the second technique, the storage modulus at a low frequency of 0.1 Hz paralleled static mechanical tests for the stainless steel alloy (183 gigapascal [GPa]), the beta-titanium alloy (64 GPa), and the Nitinol Classic (3M Unitek, Monrovia, Calif) product that represented a stable martensitic phase (41 GPa). The remaining 4 Ni-Ti products generally varied from 20 to 35 GPa when the low temperature or martensitic phase was present and from 60 to 70 GPa after the high temperature or austenitic phase had formed. CONCLUSIONS: From the clinical viewpoint, the Orthonol (Rocky Mountain Orthodontics, Denver, Colo), Cu-Ni-Ti 27, Cu-Ni-Ti 35, and Cu-Ni-Ti 40 (SDS/Ormco, Glendora, Calif) products increased at least twofold in stiffness as temperature increased, best emulating the stiffness of Nitinol Classic below the transformational temperature and the stiffness of TMA (SDS/Ormco, Glendora, Calif) above the transformational temperature. Of the 3 Cu-Ni-Ti products, the least differences were found between Cu-Ni-Ti 27 and Cu-Ni Ti 35, thereby questioning the justification for 3 similar products. PMID- 17276865 TI - Effect of blood and saliva contamination on shear bond strength of brackets bonded with 4 adhesives. AB - INTRODUCTION: The purpose of this study was to assess the effect of blood and saliva contamination on the shear bond strength of 4 orthodontic adhesives. METHODS: Four adhesives (Transbond XT primer [3M Unitek, Monrovia, Calif], Transbond Plus self-etch primer [3M Unitek], Assure hydrophilic primer [Reliance, Itasca, Ill], and SmartBond cyanoacrylate [Gestenco, Gothenburg, Sweden]) were used to bond stainless steel maxillary central incisor brackets to 120 bovine permanent mandibular incisors. The teeth were randomly divided into 12 groups of 10 specimens, and each primer-adhesive combination was tested under different enamel conditions: dry, and blood and saliva contamination after priming. Shear forces were applied to the samples with a testing machine. Bond strengths were measured in megapascals. RESULTS: Statistical evaluations showed that the shear bond strength of the SmartBond cyanoacrylate adhesive group was significantly lower than all other groups; however, it was the only adhesive that was not affected by contamination. Saliva and blood contamination resulted in significant drops in shear bond strengths of the Transbond XT and Assure groups. Transbond Plus self-etch primer was also negatively affected by blood contamination, although it was suitable for bonding with saliva contamination. PMID- 17276866 TI - Shear bond strength of an amorphous calcium-phosphate-containing orthodontic resin cement. AB - INTRODUCTION: Amorphous calcium phosphate (ACP) materials have recently been introduced with the promise of reducing demineralization around orthodontic brackets. The purpose of this in vitro study was to compare the shear bond strength of orthodontic brackets bonded with enamel using a commercially available orthodontic adhesive containing ACP to that of brackets bonded with a conventional resin-based orthodontic adhesive. METHODS: Thirty extracted molars were collected. The first group of 30 brackets was bonded to either the mesiobuccal or distobuccal tooth surface with a conventional resin-based composite adhesive. The second group of 30 brackets was bonded with the ACP adhesive to the buccal cusp that was not used by the first group. Each tooth received 2 brackets; 1 bonded with a conventional resin-based composite adhesive and the other with the ACP-containing orthodontic adhesive. Specimens were stored in water at 37 degrees C for 24 hours and then tested for shear bond strength in an Instron universal testing machine. A paired t-test was used to compare the mean shear bond strength between the 2 adhesives. The ARI scores were analyzed using the chi-squared test. All statistical tests were performed at alpha =.05. RESULTS: The t-test detected a highly significant difference in the mean shear bond strength between the 2 groups (P <.001). There was no evidence to suggest a statistical difference between the groups' ARI scores (P = .37). CONCLUSIONS: Under the conditions of this in vitro study, orthodontic brackets bonded to teeth with an ACP-containing composite material failed at significantly lower forces than brackets bonded to teeth with the conventional resin-based composite orthodontic cement. PMID- 17276867 TI - Relationship between index of complexity, outcome and need, dental aesthetic index, peer assessment rating index, and American Board of Orthodontics objective grading system. AB - INTRODUCTION: The objectives of this study were to examine the relationships among 4 indexes that are used to score orthodontic treatment need and outcome, and to determine whether 1 index could replace the other 3. The index of complexity, outcome, and need (ICON), the dental aesthetic index (DAI), the peer assessment rating (PAR) index, and the American Board of Orthodontics objective grading system (ABO-OGS) were studied. The use of the ICON is desirable because it is faster to use than separate indexes for assessing different treatment facets. METHODS: One hundred pretreatment and posttreatment study models were randomly selected from an accredited graduate orthodontic clinic at University of Illinois at Chicago, Chicago, Ill. The sample was assessed by using the PAR index, the DAI, the ABO-OGS, and the ICON. The data were analyzed descriptively and the relationships evaluated by using the Spearman rank order correlation coefficient. RESULTS: The study showed a significant correlation between the DAI and the ICON with respect to treatment need (r = .5523, P <.001). The PAR index and the ABO-OGS had significant correlations with the ICON for treatment outcome (pretreatment PAR vs ICON, r = .6840, P <.001; posttreatment PAR vs ICON, r = .3466, P <.001; ABO-OGS vs ICON, r = .2654, P <.01). CONCLUSIONS: The ICON can be used in place of the PAR and the ABO-OGS for assessing treatment outcome and in place of the DAI for assessing treatment need. PMID- 17276868 TI - Orthodontic materials research and applications: part 2. Current status and projected future developments in materials and biocompatibility. AB - The purpose of this 2-part opinion article was to project the developments expected to occur in the next few years in orthodontic materials research and applications. Part 1 reviewed developments in bonding to enamel. Part 2 looks at other orthodontic materials applications and explores emerging research strategies for probing the biological properties of materials. In the field of metallic brackets, expansion of the use of titanium alloys with improved hardness and nickel-free steels with better corrosion resistance and increased hardness is expected. Manufacturing techniques might be modified to include laser-welding methods and metal injection molding. Esthetic bracket research will involve the synthesis of high-crystallinity biomedical polymers with increased hardness and stiffness, decreased water sorption, and improved resistance to degradation. New plastic brackets might incorportate ceramic wings. Fiber-reinforced composite archwires, currently experimental, could soon be commercially available, and long term applications of shape-memory plastics might become viable. Advancements in elastomeric materials will result in polymers with reduced relaxation, broader use of fluoride-releasing elastomers with decreased relaxation, and large-scale film coating of elastomers to decrease reactivity, water sorption, and degradation. Finally, biocompatibility assessments will incorporate testing of potential endocrinological action. New polymer formulations might be tested in adhesive and plastic bracket manufacturing, based on benzoic ring-free monomers to avoid the adverse effects of the estrogenic molecule bisphenol-A. PMID- 17276869 TI - Orthodontics in 3 millennia. Chapter 13: the temporomandibular joint and orthognathic surgery. AB - The temporomandibular joint has always been the practitioner's no-man's land. Who's in charge here? The general dentist, the prosthodontist, the oral surgeon, the otolaryngologist, the psychiatrist, or the orthodontist? Theories about the cause of problems are as varied as the specialties involved. Is the cause anatomic, occlusal, neuromuscular, myofascial, psychological, or multifactorial? In another adjunctive domain, the major early advances in orthognathic surgery were the discovery of anesthesia, the experiences of World War I surgeons, and the refinement of maxillary techniques. PMID- 17276870 TI - Interdisciplinary treatment of localized juvenile periodontitis: a new perspective to an old problem. AB - What can be done for a 17-year-old girl with localized juvenile periodontitis, a Class II malocclusion, and flared teeth? Is it possible to regain epithelial attachment and rebuild the bone architecture? Is it possible to achieve good esthetics and occlusion with conventional orthodontic treatment, or is an interdisciplinary approach needed? What sequence should be followed? What is the prognosis for the affected teeth in the long term? Our aim in this article was to review the literature and present a clinical case to shed more light on the subject. PMID- 17276872 TI - Inserting a Flash movie into a PowerPoint presentation. AB - Macromedia Flash is a multimedia authoring software that is used to create dynamic presentations for the World Wide Web. Flash allows you to mix sound, animation, and graphics into a single file that can be added to a PowerPoint presentation for dynamic effect. PMID- 17276871 TI - The effectiveness of a single osteointegrated implant combined with pendulum springs for molar distalization. AB - The aim of this report was to present the clinical efficiency of a single osteointegrated implant combined with pendulum springs for molar distalization. A 15-year-old girl sought treatment for irregular anterior teeth and poor smile esthetics. A novel appliance was designed that combined osteointegrated implants with 0.032-in beta-titanium wire and pendulum springs. The treatment results were evaluated from lateral cephalometric radiographs. Distalization of the maxillary first molars was achieved in 6 months. Total treatment time was 21 months. Facial esthetics improved as a consequence of treatment. This appliance design offers reliable molar distalization, even when absolute anchorage is required. PMID- 17276873 TI - Litigation, legislation, and ethic. Integrating the fourth dimension into orthodontic administration. PMID- 17276874 TI - Foreword. PMID- 17276877 TI - Calcium-binding proteins and their role in allergic diseases. AB - Calcium-binding proteins (CBPs) are ubiquitous pollen allergens and important food allergens in fish and amphibians. Calcium-binding allergens containing two EF-hands (polcalcins) have been detected and characterized in pollen from trees, grasses, and weeds. Timothy grass Phl p 7 is the most cross-reactive allergen among polcalcins. Although there is cross-reactivity described within the subfamilies of calcium-binding allergens, there are no strong indications for IgE cross-reactivity between CBPs from plants, fish, and humans. Therefore, Phl p 7 could be used as marker to identify multiple pollen-sensitized patients, whereas cod Gad c 1 or carp Cyp c 1 could be selected for the diagnosis of fish allergy. Hom s 4, a calcium-binding autoantigen, might be an interesting candidate to monitor chronic skin inflammation in atopic and nonatopic individuals. Diagnostic tests containing these molecules could allow the identification of most patients sensitized to calcium-binding allergens/antigens. In general, IgE recognition of calcium-binding allergens is influenced by binding or release of calcium ions. This knowledge could be used to engineer hypoallergenic CBPs for specific immunotherapy. PMID- 17276878 TI - Pollen NAD(P)H oxidases and their contribution to allergic inflammation. AB - This article provides an overview of NADPH oxidase and its role in allergic inflammation. A background and historical perspectives of NADPH oxidase are first provided, followed by a detailed overview of mammalian NADPH oxidase subunits and their functional organization. Plant NADPH oxidase, the authors' discovery of NADPH oxidase in pollens, and their contribution to allergic inflammation are then discussed, concluding with a discussion of future directions and outstanding questions that require attention. PMID- 17276879 TI - Impact of native, recombinant, and cross-reactive allergens on humoral and T-cell mediated immune responses. AB - Many native allergens have been purified to homogeneity from natural sources, and whole arrays of recombinant and cross-reactive allergens have been produced in large amounts as biologically active molecules. These allergens offer potent research tools to investigate humoral and T cell-mediated immune responses to allergens in healthy and allergic individuals, providing methods for verifying the responses in a reproducible and dose-dependent manner. Dissecting the immune responses to allergens at cellular and molecular levels provides models for studying the different aspects of T-cell activation and the development of immunologic memory and effector functions. A deep understanding of these mechanisms will fundamentally change the current practice of allergy diagnosis, treatment, and prevention. PMID- 17276880 TI - Recognition of lipids from pollens by CD1-restricted T cells. AB - Allergic rhinitis and asthma should be considered as organ-specific inflammatory diseases in which the genetic background has determined a local overproduction of Th2-type cytokines and an over-expansion of particular APCs and T cells. Among the latter, a potential pathogenetic role could be assumed for natural killer T cells, expressing both invariant (Valpha24/Vbeta11) and classic alphabeta or gammadelta T-cell receptors. Recent studies support this notion and also suggest that surface pollen substances of nonprotein structure, such as lipid components recognized by CD1, could be viewed as one of the foreign materials against which the immune system of the allergic subject can mount a local inflammatory response. PMID- 17276876 TI - Bioinformatics approaches to classifying allergens and predicting cross reactivity. AB - Allergenic proteins from very different environmental sources have similar sequences and structures. This fact may account for multiple allergen syndromes, whereby a myriad of diverse plants and foods may induce a similar IgE-based reaction in certain patients. Identifying the common triggering protein in these sources, in silico, can aid designing individualized therapy for allergen sufferers. This article provides an overview of databases on allergenic proteins, and ways to identify common proteins that may be the cause of multiple allergy syndromes. The major emphasis is on the relational Structural Database of Allergenic Proteins (SDAP []), which includes cross-referenced data on the sequence, structure, and IgE epitopes of over 800 allergenic proteins, coupled with specially developed bioinformatics tools to group all allergens and identify discrete areas that may account for cross-reactivity. SDAP is freely available on the Web to clinicians and patients. PMID- 17276881 TI - Chimeric human fcgamma-allergen fusion proteins in the prevention of allergy. AB - Allergic responses are strongly associated with Th2-type immune responses, and modulation of the skewed Th2 response toward a more balanced response is the major goal of allergen immunotherapy (IT) in allergic disorders. To achieve this goal, several approaches have been tested. The authors previously showed that a human immunoglobulin (Ig) Fcgamma-Fcvarepsilon fusion protein (GE2) that directly cross-links FcvarepsilonRI and FcgammaRIIb on human mast cells and basophils was able to inhibit degranulation, and they reasoned that human gamma-allergen fusion protein would achieve a similar inhibitory effect in an allergen-specific fashion while preserving the immunogenicity of the allergen component. Therefore, the authors constructed and developed a human-cat chimeric fusion protein composed of the human Fcgamma1 and the cat allergen Fel d1 (Felis domesticus) for cat allergen-specific IT. This article summarizes the therapeutic features and potential of this novel fusion protein for allergic IT. PMID- 17276883 TI - A rice-based edible vaccine expressing multiple T-cell epitopes to induce oral tolerance and inhibit allergy. AB - Plant pollens are the most common cause of seasonal allergic disease. The number of patients undergoing treatment for allergies to the pollen of Japanese cedar (major antigens, Cry j 1 and Cry j 2) has increased steadily each year. A rice seed-based edible vaccine has been shown to be effective for treating Japanese cedar pollinosis. Rice seeds containing the major T-cell epitopes derived from cedar pollen allergens were orally administrated to mice before systemic challenge with total pollen protein. Mucosal immune tolerance leading to a reduction of allergen-specific IgE, T-cell proliferative reactions, and histamine were induced, resulting in suppression of allergy-specific symptoms such as sneezing. Oral seed-based peptide immunotherapy offers a safe, simple, and cost effective alternative to conventional allergen-specific immunotherapy using crude allergen extracts for treating allergic disease. A human version of rice seed based edible vaccine containing seven T-cell epitopes from the Cry j 1 and Cry j 2 allergens was recently developed and is undergoing safety assessments. PMID- 17276884 TI - Commentary from the editor. PMID- 17276882 TI - New perspectives for use of native and engineered recombinant food proteins in treatment of food allergy. AB - Food allergy has emerged as an important target for research on curative treatment and prevention, with most efforts focusing on peanut, cow's milk, and egg allergy. This article reviews the recent developments in the potential treatments for IgE-mediated food allergy using native and engineered recombinant food proteins. PMID- 17276886 TI - Chlamydia pneumoniae stimulates the proliferation of HUVEC through the induction of VEGF by THP-1. AB - Chlamydia pneumoniae, a gram-negative bacterium, is an important human intracellular pathogen; studies of C. pneumoniae pathogenesis have shown that the organism can infect many cell types associated with both respiratory and vascular sites, including arterial smooth muscle cells, macrophages and vascular endothelium. Recently, the recognition of atherosclerosis as an inflammatory disease in its genesis, progression and ultimate clinical manifestations has created an interesting area of vascular research. We assessed the hypothesis that growth factors from THP-1 macrophages infected with C. pneumoniae are involved in the regulation of cell proliferation in HUVEC. The induction of these factors were dependent on time of infection, as medium harvested 48 h after infection had a greater activity than media harvested at 12 or 24 h after infection. Heat killed C. pneumoniae produced similar results to those of live bacteria. In addition, conditioned medium filtered sterile from infected macrophages induced the proliferation of HUVEC, thus demonstrating its angiogenic potential. Moreover, pretreatment of macrophages with cytochalasin D, a phagocytosis inhibitor, yielded almost comparable results, suggesting that bacterium cell attachment is sufficient for VEGF, IL-1beta and IL-8 induction. Further studies are necessary to elucidate the biological role of chlamydial involvement in the complex and mutifactored processes of angiogenesis and possibly contribute to the development of therapeutic strategies. PMID- 17276885 TI - Histamine affects STAT6 phosphorylation via its effects on IL-4 secretion: role of H1 receptors in the regulation of IL-4 production. AB - Signal Transducer and Activator of Transcription (STAT)-6 is a transcriptional factor activated mainly through the cytokines IL-4 and IL-13 leading to the Th2 cell differentiation. Th2 cells play a role in the etiology and pathogenesis of allergic disease. Histamine alters the Th1/Th2 cytokine balance towards the Th2 cytokine profile and consequently plays a role in allergic diseases and asthma. This study was designed to investigate the effects of histamine on the STAT6 phosphorylation. C57/BL6 splenocytes were pretreated with different concentrations of histamine (10(-)(4) M to 10(-)(13) M) followed by stimulation with PMA+ionomycin or IL-4. The phosphorylated and total basal STAT6 levels were assessed by employing the immunoblotting technique. Histamine caused the hyper phosphorylation of STAT6. H1 receptor antagonist pyrilamine reversed the effect of histamine on STAT6 phosphorylation. However, H2 receptor antagonist ranitidine and H3/H4 receptor antagonist thioperamide did not affect the histamine mediated hyper-phosphorylation of STAT6. Furthermore, H1 receptor agonist betahistine enhanced the phosphorylation of STAT6 whereas H2 receptor agonist amthamine did not affect the phosphorylation STAT6. Furthermore, tyrosine kinase inhibitor, tyrphostin, inhibited the histamine mediated phosphorylation of STAT6 when stimulated with PMA+ionomycin. The effects of histamine on the STAT6 phosphorylation were indirect since they were blocked either by the antibodies to IL-4 and IL-13 or in IL-4 knock out mice in the presence of IL-13 antibody. These observations suggest that histamine indirectly affected the STAT6 phosphorylation via its effects on the secretion of cytokines (IL-4) and H1 receptor played a role in this process. PMID- 17276888 TI - Antibody response against neem leaf preparation recognizes carcinoembryonic antigen. AB - An immune serum generated in Swiss mice against an aqueous preparation from neem leaf was reactive with carcinoembryonic antigen (CEA) and a peptide sequence derived from it. Using ELISA, we have demonstrated that CEA reactive antibody titer (chiefly IgG2a) was significantly decreased after absorption of the immune sera with CEA. Neem leaf preparation (NLP) generated immune sera was also reactive with CEA in immunoblotting and CEA reactive component in the NLP sera can be immunoprecipitated. Identical recognition of CEA expressed on human colorectal cancer specimens, by anti-CEA monoclonal antibody and NLP sera was documented by immunohistochemistry. NLP generated sera could also react with NLP in ELISA and this reactivity was decreased after absorption of the NLP with anti CEA antibody. Estimation of protein in NLP revealed the presence of it, at least 10% of the total dry weight. In addition, existence of flavone and quercetin was also evidenced from LC-MS analysis. Further studies are needed to identify the antigenic component may have some homology with CEA molecule. This unique property of neem may be utilized for the immunotherapy of CEA positive tumors. PMID- 17276887 TI - Antiangiogenic activity of Diallyl Sulfide (DAS). AB - Antiangiogenic activity of Diallyl sulfide (DAS) was studied using in vivo as well as in vitro models. In vivo antiangiogenic activity was studied using B16F 10 melanoma cell induced capillary formation in C57BL/6 mice. DAS significantly inhibited tumour directed capillary formation. Studies of serum cytokine profile of angiogenesis induced animals clearly showed that DAS significantly reduced the production of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha and GM CSF which are known proangiogenic factors. The serum level of VEGF, an important proangiogenic factor, in angiogenesis induced animals was found to be significantly reduced upon treatment with DAS which may be due to its efficacy in the down regulation of VEGF mRNA expression. Administration of DAS significantly enhanced the production of antiangiogenic factors such as IL-2 and TIMP. In vitro studies using rat aortic ring assay showed that administration of DAS at no n toxic concentrations significantly inhibited microvessel sprouting. Studies using Human umbilical vein endothelial cells (HUVECs) clearly demonstrated that administration of DAS significantly retarded endothelial cell proliferation, migration, invasion and tube formation. These data clearly suggests that antiangiogenic activity of DAS can be related to its negative regulation of proangiogenic factors such as VEGF and proinflammatory cytokines and positive regulation of antiangiogenic factors such as IL-2 and TIMP. PMID- 17276889 TI - Differential effects of ginsenosides on NO and TNF-alpha production by LPS activated N9 microglia. AB - Ginsenosides, the main active components of ginseng, have been reported to exert neuroprotective effects in the central nervous system. In this report, the effects of ginsenoside-Rd and -Rb2, two protopanaxadiols, and ginsenoside-Rg1 and -Re, two protopanaxatriols, on the production of nitric oxide (NO) and TNF-alpha (TNF-alpha) by lipopolysaccharide (LPS)-activated N9 microglial cells were studied. All ginsenosides studied potently suppressed TNF-alpha production in LPS activated N9 cells. Ginsenoside-Rg1 and -Re, but not ginsenoside-Rb2 and -Rd, inhibited the production of NO in LPS-activated N9 cells. Ginsenosides inhibited the phosphorylation of c-Jun NH2-terminal kinase (JNK), c-Jun and extracellular signal-regulated kinase (ERK), The findings herein show that the inhibition of LPS-induced ERK1/2 and JNK activation may be a contributing factor to the main mechanisms by which ginsenosides inhibits RAW264.7. To clarify the mechanistic basis for its ability to inhibit TNF-alpha and NO induction, the effect of ginsenosides on transcription factor NF-kappaB protein level was also examined. These activities were associated with the down-regulation of inhibitor kappaB (IkappaB). These findings suggest that the inhibition of LPS-induced NO formation and TNF-alpha production in microglia by ginsenosides is due to its inhibition of NF-kappaB, which may be the mechanistic basis for the anti-inflammatory effects of ginsenosides. The significant suppressive effects of ginsenosides on proinflammatory responses of microglia implicate their therapeutic potential in neurodegenerative diseases accompanied by microglial activation. PMID- 17276890 TI - BCG-infected adherent mononuclear cells release cytokines that regulate group 1 CD1 molecule expression. AB - Increasing evidence is now available showing that CD1-restricted T cell responses against non-peptide mycobacterial antigens could play a role in the immune resistance against tuberculosis. BCG, widely used in anti-tubercular vaccination, shares various constituents with Mycobacterium tuberculosis, but does not provide full protection. In the present study we have investigated the pattern of group 1 CD1 molecule expression in adherent mononuclear cells (AMNC) of human peripheral blood, infected in vitro with BCG. Shortly after exposure to BCG, both BCG positive and BCG-negative AMNC showed a moderate CD1 expression elicited by BCG induced release of GM-CSF presumably acting through an autocrine and a paracrine mechanism. This was demonstrated using two-color flow cytometry with green fluorescent BCG and anti-CD1 PE-labeled antibodies. However, high CD1 expression induced by exogenously added GM-CSF in AMNC was reduced if target cells were cocultivated with BCG. Monoclonal antibodies against IL-10 partially restored CD1 expression, thus showing that IL-10, released from infected AMNC, is involved, at least in part, in CD1 negative modulation. Therefore, through a complex cytokine network, including not yet identified factor(s), BCG triggers but does not allow full expression of CD1 on AMNC. It cannot be excluded that this mechanism could play a role in the limited efficiency of BCG vaccination. PMID- 17276891 TI - Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. AB - Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and up-regulation of pro inflammatory cytokines. Mitogen-activated protein kinases (MAPKs), such as the p38 and the c-Jun N-terminal kinase (JNK) modulate the transcription of many genes involved in the inflammatory process. Curcumin is a polyphenol derived from Curcuma longa, which is known to have anti-inflammatory activity. The aim of this study was to study the effects and mechanisms of action of curcumin, on chronic colitis in rats. Inflammation response was assessed by histology and myeloperoxidase activity (MPO). We determined the production of Th1 and Th2 cytokines and nitrites in colon mucosa, as well as the expression of inducible nitric oxide synthase (iNOS), cyclo-oxygenase(COX)-1 and-2 by western blotting and inmmunohistochemistry. Finally, we studied the involvement of MAPKs signaling in the protective effect of curcumin in chronic colonic inflammation. Curcumin (50-100 mg/kg/day) were administered by oral gavage 24 h after trinitrobenzensulfonic acid (TNBS) instillation, and daily during 2 weeks before sacrifice. Curcumin significantly attenuated the damage and caused substantial reductions of the rise in MPO activity and tumour necrosis factor alpha (TNF) alpha. Also curcumine was able to reduce nitrites colonic levels and induced down regulation of COX-2 and iNOS expression, and a reduction in the activation of p38 MAPK; however, no changes in the activation of JNK could be observed. In conclusion, we suggest that inhibition of p38 MAPK signaling by curcumin could explain the reduced COX-2 and iNOS immunosignals and the nitrite production in colonic mucosa reducing the development of chronic experimental colitis. PMID- 17276893 TI - Induction of immune tolerance by oral IVIG. AB - In the last years evidence has been provided for the importance of B cells in the pathogenesis of rheumatoid arthritis (RA). Several studies have supported the concept that humoral immunity, manifested by the production of autoantibodies, such as rheumatoid factors (RFs), plays a significant role in the course of the disease. Specific targeting of autoantibody-producing B cells, such as RF producing B cells, should therefore be a promising new approach in the treatment of RA. We used a mouse model to induce human RF responses and asked the question whether oral treatment with the antigen (human IgG) recognized by RFs could induce immune tolerance to RF responses. Balb/c mice were orally treated with polyvalent human IgG before and after immunization with insoluble immune complexes (ICs) that triggered the induction of RFs. Serum titers of RFs were significantly reduced after both primary and booster immunization when human IgG was given as a single oral dose or continuously in drinking water. Continuous treatment with human IgG even prevented booster effects on RFs when treatment started after primary immunization. Treatment with IgG fragments provided evidence that the observed effect of human IgG was mediated by the Fc part and not the Fab part of IgG. Furthermore, transfer of spleen cells obtained from mice after oral treatment with human IgG suppressed RF responses in recipient mice. These data give promising indications that oral human IgG might represent an alternative approach for immunosuppressive B-cell targeted therapies in RA. PMID- 17276892 TI - Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-kappaB signaling pathways. AB - Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of the traditionally used Chinese herb Paeonia lactiflora Pallas, has anti-inflammatory, antioxidant and cardiovascular protective activities. We studied how the levels of intercellular adhesion molecule-1 (ICAM-1), one of the key molecules in the development of atherosclerosis, might be affected by paeonol in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Paeonol concentration-dependently inhibited the production of ICAM-1; it inhibited nuclear factor-kappaB (NF-kappaB) p65 translocation into the nucleus and the phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also blocked the TNF-alpha-induced phosphorylation of p38 and extracellular signal regulated kinase (ERK), which are involved in regulating ICAM-1 production by TNF alpha. Paeonol inhibited U937 monocyte adhesion to HUVECs stimulated by TNF alpha, suggesting that it may inhibit the binding of monocytes to endothelium by regulating the production of critical adhesion molecules by TNF-alpha. The inhibitory effect of paeonol on ICAM-1 production might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways, which are involved in TNF-alpha induced ICAM-1 production. Thus, paeonol may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis. PMID- 17276895 TI - Nasal decongestion test in allergic rhinitis: definition of responder. AB - BACKGROUND: Nasal airflow, as measured by rhinomanometry, is frequently impaired in allergic rhinitis (AR). The decongestion test evaluates whether the application of an intranasal vasoconstrictor drug increases nasal airflow. OBJECTIVE: The aim of this study was to define the characteristics of decongestion test responders. METHODS: 123 subjects (112 males and 11 females, mean age 22.9+/-5.7 years) with AR were studied. Nasal eosinophils, rhinomanometry, and decongestion test were assessed in all subjects. RESULTS: The optimal cut-off for % variation of nasal airflow and nasal eosinophils >5 was = 34.4, with sensibility = 82.7% (95%CI 73.7-89.6) and specificity = 80% (95%CI 59.3-93.1). CONCLUSIONS: The clinical relevance of this study is that non responders may have a likely moderate-severe allergic inflammation that should be adequately evaluated and treated. PMID- 17276894 TI - Temporal variation in CB2R levels following T lymphocyte activation: evidence that cannabinoids modulate CXCL12-induced chemotaxis. AB - Cannabinoids have long been proposed to affect the immune system, especially as one of the cannabinoid receptors, the cannabinoid receptor-2 (CB(2)R) has been found almost exclusively on immune cells. Here, using human in vitro activated peripheral blood-derived T lymphocytes we investigated the long-term changes in cannabinoid receptor protein expression following cellular activation and the effects of cannabinoids on migration. We report that resting T lymphocytes do not detectably express either the cannabinoid receptor-1 (CB(1)R) or CB(2)R at the protein level. However, CB(2)R protein expression is upregulated in a biphasic manner in T lymphocytes following activation by superantigen. The cannabinoids 2 AG and JWH-133 were found to elicit activation of downstream biochemical effectors (as assessed by the phosphorylation of the ERK1/2 MAP kinases). Neither 2-AG nor JWH-133 induced chemotaxis in day 5 activated T lymphocytes, when receptor expression was at its highest. Interestingly, both 2-AG and JWH-133 inhibited CXCL12-induced chemotaxis, suggesting a modulatory role for cannabinoids in activated T lymphocytes. PMID- 17276896 TI - The effects of the EW dipeptide optical and chemical isomers on the CFU-S population in intact and irradiated mice. AB - The influence of Glu-Trp (EW) synthetic dipeptide isomers on hemopoietic progenitor cells and certain immune response reactions is determined by their optical and chemical properties. Thus, the all L-amino acid containing dipeptides L-Glu-L-Trp and L-gammaGlu-L-Trp have no effect on proliferation of committed and pluripotent CFU-S in intact bone marrow. The optical isomers of the Glu residue are an essential determinant of the EW dipeptide biological activity. The inversion of the amino acid optical form imparts suppressor properties: D-Glu-D Trp,D--gammaGlu-D-Trp, D-Glu-L-Trp and D-gammaGlu-L-Trp inhibit proliferation of hemopoietic progenitors in intact bone marrow. The type of the peptide bond between L-Glu and Trp is another important factor for the biological activity of the L-Glu-containing peptides. Unlike L-Glu-D-Trp with alpha-peptide bond, the dipeptide L-gammaGlu-D-Trp with gamma-peptide bond stimulates CFU-S-8 proliferation in intact bone marrow. The diverse effects of the EW optical isomers on hemopoietic progenitors underlie the radioprotective properties of the D-Glu-containing dipeptides and the radiotherapeutic ones of the L-Glu dipeptides. In animals, pre-irradiation injection of D-Glu-D-Trp, D-gammaGlu-D Trp, D-Glu-L-Trp, D-gammaGlu-L-Trp, or post-irradiation injection of L-Glu-L-Trp, L-gammaGlu-L-Trp promoted regeneration of the hemopoietic progenitor population. PMID- 17276897 TI - Induction of inflammatory cytokines by cartilage extracts. AB - Shark cartilage extracts were examined for induction of cytokines and chemokines in human peripheral blood leukocytes. Primary leukocyte cultures were exposed to a variety of aqueous and organic extracts prepared from several commercial brands of shark cartilage. From all commercial sources of shark cartilage tested the acid extracts induced higher levels of TNFalpha than other extracts. Different commercial brands of shark cartilage varied significantly in cytokine-inducing activity. TNFalpha induction was seen as early as 4 h and IFNgamma at detectable levels for up to four days. Shark cartilage extracts did not induce physiologically significant levels of IL-4. Results suggest that shark cartilage, preferentially, induces Th1 type inflammatory cytokines. When compared to bovine cartilage extract, collagen, and chondroitin sulfate, shark cartilage induced significantly higher levels of TNFalpha. Treatment with digestive proteases (trypsin and chymotrypsin) reduced the cytokine induction response by 80%, suggesting that the active component(s) in cartilage extracts is proteinaceous. The induction of Th1 type cytokine response in leukocytes is a significant finding since shark cartilage, taken as a dietary supplement for a variety of chronic degenerative diseases, would be contraindicated in cases where the underlying pathology of the chronic condition is caused by inflammation. PMID- 17276898 TI - Inhibition of infection caused by severe acute respiratory syndrome-associated coronavirus by equine neutralizing antibody in aged mice. AB - The high susceptibility of elderly to severe acute respiratory syndrome associated coronavirus (SARS-CoV) indicates how crucial it is to protect the elderly by various strategies. Aged BALB/c mice displayed a high susceptibility to SARS-CoV and have been a valuable platform for evaluation of strategies against SARS-CoV infection. In this study, we confirmed the validity of this model using various methods, and verified that equine anti-SARS-CoV F(ab')(2) can prevent aged animals from SARS-CoV infection. In a therapeutic setting, treatment with anti-SARS-CoV F(ab')(2) decreased viral load more than several thousand folds in the lungs. Thus, this antibody should be a potential candidate for treatment of elderly patients suffering from SARS. PMID- 17276899 TI - Characterization and anti-tumor activity of pollen polysaccharide. AB - The polysaccharide LBPP was extracted and isolated from the pollen of Brassica napus L., and the anti-tumor activity was evaluated on Sarcoma 180-bearing mice and B16 melanoma-bearing mice through transplantable animal tumor. Mice were treated with three doses of the polysaccharide LBPP (50, 100 and 200 mg/kg body weight) for 10 days. Tumor weight, relative spleen and thymus weight, lymphocyte proliferation, natural killer cell activity, delayed type hypersensitivity (DTH), phagocytic function of monocyte, serum hemolysis antibody and peripheral blood of tumor-bearing mice were studied. At the doses of 100 and 200 mg/kg, a significant decrease (P<0.01) in tumor formation, a significant increase (P<0.05) in relative spleen and thymus weight, natural killer cell activity, phagocytic function of monocyte, lymphocyte proliferation, and serum hemolysis antibody, and a significant improvement of peripheral blood abnormality (P<0.05) and anemia (P<0.01) were observed. Results of these studies demonstrated that the polysaccharide LBPP had anti-tumor activity, which was mediated by immunomodulation and leukogenic and antianemic actions. PMID- 17276900 TI - Sea turtles: navigating with magnetism. AB - Young sea turtles use the Earth's magnetic field as a source of navigational information during their epic transoceanic migrations and while homing. A new study using satellite telemetry has now demonstrated for the first time that adult turtles also navigate using the Earth's magnetic field. PMID- 17276901 TI - Bonobos. PMID- 17276902 TI - Drosophila melanogaster's history as a human commensal. PMID- 17276903 TI - Increased outbreeding in yeast in response to dispersal by an insect vector. PMID- 17276904 TI - Crayfish respond to electrical fields. PMID- 17276905 TI - Invertebrate memory: wide-eyed ants retrieve visual snapshots. AB - Ants retrieve visual memories to guide them en route to their goal. A new study shows that wood ants use object width to retrieve the correct visual memory at the appropriate position along their route. A computational model that accurately reproduces the ants' behaviour raises questions about the underlying mechanisms. PMID- 17276906 TI - Fungal pathogenesis: gene clusters unveiled as secrets within the Ustilago maydis code. AB - The genome sequence of a second plant pathogenic fungus is now available, revealing unique gene clusters encoding secretory proteins that are induced during infection and regulate pathogenesis. Gene clusters play important roles in pathogenic fungi, yet their evolution and maintenance remain a mystery. PMID- 17276907 TI - Evolution: lending a helping hand in sperm competition? AB - Most females mate with many males. This can be costly, but the benefits to females are often unclear. A new study raises the possibility that females could benefit through an unconventional genetic pathway, while also showing that males can inadvertently increase rival males' fitness in surprising ways. PMID- 17276909 TI - Cognitive training: neural correlates of expert skills. AB - Expertise is a ubiquitous pre-requisite for modern life, but little is known about what neural mechanisms underpin the acquisition or employment of such skills. Recent evidence from functional magnetic imaging studies suggests that a network of frontal and parietal regions plays a crucial role. PMID- 17276908 TI - Cell division: mid-level management. AB - When a fission yeast cell divides, the anillin-like protein mid1p helps to position the contractile ring in the cell middle. Recent experiments from two groups have shown how the cell-polarity factor pom1p negatively regulates the distribution of mid1p. PMID- 17276910 TI - Genome evolution: a double take for Paramecium. AB - The surprising discovery of a whole-genome duplication in the otherwise compact genome of Paramecium tetraurelia displays the early forces driving gene retention and loss. PMID- 17276911 TI - Extra-retinal vision: firing at will. AB - Recent evidence suggests that a key visual motion centre in the brain ignores extra-retinal motor information concerning reflexive eye movement. Instead it seems that neurons sensitive to oculomotor actions in this area fire at will. PMID- 17276912 TI - Intraflagellar transport protein 27 is a small G protein involved in cell-cycle control. AB - BACKGROUND: Intraflagellar transport (IFT) is a motility process operating between the ciliary/flagellar (interchangeable terms) membrane and the microtubular axoneme of motile and sensory cilia. Multipolypeptide IFT particles, composed of complexes A and B, carry flagellar precursors to their assembly site at the flagellar tip (anterograde) powered by kinesin, and turnover products from the tip back to the cytoplasm (retrograde) driven by cytoplasmic dynein. IFT is essential for the assembly and maintenance of almost all eukaryotic cilia and flagella, and mutations affecting either the IFT motors or the IFT particle polypeptides result in the inability to assemble normal flagella or in defects in the sensory functions of cilia. RESULTS: We found that the IFT complex B polypeptide, IFT27, is a Rab-like small G protein. Reduction of the level of IFT27 by RNA interference reduces the levels of other complex A and B proteins, suggesting that this protein is instrumental in maintaining the stability of both IFT complexes. Furthermore, in addition to its role in flagellar assembly, IFT27 is unique among IFT polypeptides in that its partial knockdown results in defects in cytokinesis and elongation of the cell cycle and a more complete knockdown is lethal. CONCLUSION: IFT27, a small G protein, is one of a growing number of flagellar proteins that are now known to have a role in cell-cycle control. PMID- 17276913 TI - The C. elegans glycopeptide hormone receptor ortholog, FSHR-1, regulates germline differentiation and survival. AB - BACKGROUND: The mammalian glycopeptide hormone receptors (GPHRs) are key regulators of reproductive development, and their homologs are widely distributed throughout the animal kingdom. The C. elegans genome encodes a single GPHR family member, FSHR-1, which shares equal identity to the FSH, LH, and TSH receptors from mammals. RESULTS: Because loss of fshr-1 function does not produce a visible phenotype in C. elegans, we conducted a genome-wide RNAi-feeding screen to identify genes that perform functions that overlap with those of fshr-1. This approach led to the identification of the PUF family members fbf-1 and fbf-2 (the fbfs). Whereas a weak reduction in fbf activity caused little or no discernable effect in the wild-type, an equivalent loss in the fshr-1(0) mutant background resulted in a highly penetrant germline-masculinization phenotype. Furthermore, many fshr-1(0);fbf(RNAi) animals failed to maintain a germline stem cell niche. We also show that fshr-1 and the fbfs promote germline survival and prevent apoptosis with fog-1 and fog-3 and that simultaneous loss of fshr-1 and the fbfs can override the canonical requirement for fog-1 and fog-3 in the execution of the male-germline fate. Finally, we provide evidence that FSHR-1 controls germline processes nonautonomously via the soma and that FSHR-1 acts through a canonical signaling pathway involving Galpha(s) and adenyl cyclase. CONCLUSIONS: Our results indicate a conserved role for GPHR family receptors in controlling germline development and fertility. Our data suggest a model whereby FSHR-1 signaling acts in parallel to the known sex-determination pathway to control multiple aspects of germline development. PMID- 17276915 TI - Active inbreeding in a cichlid fish and its adaptive significance. AB - Levels of inbreeding are highly variable in natural populations. Inbreeding can be due to random factors (like population size), limited dispersal, or active mate choice for relatives. Because of inbreeding depression, mating with kin is often avoided, although sometimes intermediately related individuals are preferred (optimal outbreeding). However, theory predicts that the advantages of mating with close kin can override the effects of inbreeding depression, but in the animal kingdom, empirical evidence for this is scarce. Here we show that both sexes of Pelvicachromis taeniatus, an African cichlid with biparental brood care, prefer mating with unfamiliar close kin over nonkin, suggesting inclusive fitness advantages for inbreeding individuals. Biparental care requires synchronous behavior among parents. Since parental care is costly, there is a conflict between parents over care, which can reduce offspring fitness. Relatedness is expected to enhance cooperation among individuals. The comparison of the parental behavior of in- and outbreeding pairs showed that related parents were more cooperative and invested more than unrelated parents. Since we found no evidence for inbreeding depression, our results suggest that in P. taeniatus, inbreeding is an advantageous strategy. PMID- 17276914 TI - A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest. AB - BACKGROUND: Vertebrate oocytes are arrested in metaphase II of meiosis prior to fertilization by cytostatic factor (CSF). CSF enforces a cell-cycle arrest by inhibiting the anaphase-promoting complex (APC), an E3 ubiquitin ligase that targets Cyclin B for degradation. Although Cyclin B synthesis is ongoing during CSF arrest, constant Cyclin B levels are maintained. To achieve this, oocytes allow continuous slow Cyclin B degradation, without eliminating the bulk of Cyclin B, which would induce release from CSF arrest. However, the mechanism that controls this continuous degradation is not understood. RESULTS: We report here the molecular details of a negative feedback loop wherein Cyclin B promotes its own destruction through Cdc2/Cyclin B-mediated phosphorylation and inhibition of the APC inhibitor Emi2. Emi2 bound to the core APC, and this binding was disrupted by Cdc2/Cyclin B, without affecting Emi2 protein stability. Cdc2 mediated phosphorylation of Emi2 was antagonized by PP2A, which could bind to Emi2 and promote Emi2-APC interactions. CONCLUSIONS: Constant Cyclin B levels are maintained during a CSF arrest through the regulation of Emi2 activity. A balance between Cdc2 and PP2A controls Emi2 phosphorylation, which in turn controls the ability of Emi2 to bind to and inhibit the APC. This balance allows proper maintenance of Cyclin B levels and Cdc2 kinase activity during CSF arrest. PMID- 17276916 TI - A role for NuSAP in linking microtubules to mitotic chromosomes. AB - The spindle apparatus is a microtubule (MT)-based machinery that attaches to and segregates the chromosomes during mitosis and meiosis. Self-organization of the spindle around chromatin involves the assembly of MTs, their attachment to the chromosomes, and their organization into a bipolar array. One regulator of spindle self-organization is RanGTP. RanGTP is generated at chromatin and activates a set of soluble, Ran-regulated spindle factors such as TPX2, NuMA, and NuSAP . How the spindle factors direct and attach MTs to the chromosomes are key open questions. Nucleolar and Spindle-Associated Protein (NuSAP) was recently identified as an essential MT-stabilizing and bundling protein that is enriched at the central part of the spindle . Here, we show by biochemical reconstitution that NuSAP efficiently adsorbs to isolated chromatin and DNA and that it can directly produce and retain high concentrations of MTs in the immediate vicinity of chromatin or DNA. Moreover, our data reveal that NuSAP-chromatin interaction is subject to Ran regulation and can be suppressed by Importin alpha (Impalpha) and Imp7. We propose that the presence of MT binding agents such as NuSAP, which can be directly immobilized on chromatin, are critical for targeting MT production to vertebrate chromosomes during spindle self-organization. PMID- 17276917 TI - Nocturnal male sex drive in Drosophila. AB - Many behaviors and physiological processes including locomotor activity, feeding, sleep, mating, and migration are dependent on daily or seasonally reoccurring, external stimuli. In D. melanogaster, one of the best-studied circadian behaviors is locomotion. The fruit fly is considered a diurnal (day active/night inactive) insect, based on locomotor-activity recordings of single, socially naive flies. We developed a new circadian paradigm that can simultaneously monitor two flies in simple social contexts. We find that heterosexual couples exhibit a drastically different locomotor-activity pattern than individual males, females, or homosexual couples. Specifically, male-female couples exhibit a brief rest phase around dusk but are highly active throughout the night and early morning. This distinct locomotor-activity rhythm is dependent on the clock genes and synchronized with close-proximity encounters, which reflect courtship, between the male and female. The close-proximity rhythm is dependent on the male and not the female and requires circadian oscillators in the brain and the antenna. Taken together, our data show that constant exposure to stimuli emanating from the female and received by the male olfactory and other sensory systems is responsible for the significant shift in intrinsic locomotor output of socially interacting flies. PMID- 17276918 TI - A mutation in zebrafish hmgcr1b reveals a role for isoprenoids in vertebrate heart-tube formation. AB - In vertebrates, the morphogenetic assembly of the primitive heart tube requires the medial migration and midline fusion of the bilateral myocardial epithelia. Several mutations that result in abnormal heart-tube formation have been studied; however, an understanding of the underlying molecular and cellular mechanisms of the migration and fusion of these epithelial sheets is far from complete. In a forward genetic screen to identify genes regulating early zebrafish heart development, we identified a mutation in the 3-hydroxy-3-methylglutaryl-Coenzyme A reductase 1b (hmgcr1b) gene that affects myocardial migration to the midline and subsequent heart-tube morphogenesis. The mutant phenotype can be rescued with injections of mevalonate, the direct product of HMGCR activity. Furthermore, treatment of embryos with pharmacological inhibitors of isoprenoid synthesis, which occurs downstream of mevalonate production, resulted in defective heart tube formation. Interestingly, in hmgcr1b mutant embryos and embryos treated with HMGCR inhibitors, both RasCT20-eGFP and RhoaCT32-eGFP fusion proteins were mislocalized away from the plasma membrane in embryonic myocardial cells. We conclude that protein prenylation, acting downstream of Hmgcr1b and possibly through Ras and, or, Rho signaling, is required for the morphogenesis of the myocardial sheets for formation of the primitive heart tube. PMID- 17276919 TI - Mechanisms of spindle-pole organization are influenced by kinetochore activity in mammalian cells. AB - The spindle is a fusiform bipolar-microtubule array that is responsible for chromosome segregation during mitosis. Focused poles are an essential feature of spindles in vertebrate somatic cells, and pole focusing has been shown to occur through a centrosome-independent self-organization mechanism where microtubule motors cross-link and focus microtubule minus ends. Most of our understanding of this mechanism for pole focusing derives from studies performed in cell-free extracts devoid of centrosomes and kinetochores. Here, we examine how sustained force from kinetochores influences the mechanism of pole focusing in cultured cells. We show that the motor-driven self-organization activities associated with NuMA (i.e., cytoplasmic dynein) and HSET are not necessary for pole focusing if sustained force from kinetochores is inhibited in Nuf2- or Mis12-deficient cells. Instead, pole organization relies on TPX2 as it cross-links spindle microtubules to centrosome-associated mitotic asters. Thus, both motor-driven and static-cross linking mechanisms contribute to spindle-pole organization, and kinetochore activity influences the mechanism of spindle-pole organization. The motor-driven self-organization of microtubule minus ends at spindle poles is needed to organize spindle poles in vertebrate somatic cells when kinetochores actively exert force on spindle microtubules. PMID- 17276920 TI - Filament formation of the Escherichia coli actin-related protein, MreB, in fission yeast. AB - Proteins structurally related to eukaryotic actins have recently been identified in several prokaryotic organisms. These actin-like proteins (MreB and ParM) and the deviant Walker A ATPase (SopA) play a key role in DNA segregation and assemble into polymers in vitro and in vivo. MreB also plays a role in cellular morphogenesis. Whereas the dynamic properties of eukaryotic actins have been extensively characterized, those of bacterial actins are only beginning to emerge. We have established the fission yeast Schizosaccharomyces pombe as a cellular model for the functional analysis of the Escherichia coli actin-related protein MreB. We show that MreB organizes into linear bundles that grow in a symmetrically bidirectional manner at 0.46 +/- 0.03 microm/min, with new monomers and/or oligomers being added along the entire length of the bundle. Organization of linear arrays was dependent on the ATPase activity of MreB, and their alignment along the cellular long axis was achieved by sliding along the cortex of the cylindrical part of the cell. The cell ends appeared to provide a physical barrier for bundle elongation. These experiments provide new insights into the mechanism of assembly and organization of the bacterial actin cytoskeleton. PMID- 17276921 TI - Male-killing bacteria trigger a cycle of increasing male fatigue and female promiscuity. AB - Sex-ratio distorters are found in numerous species and can reach high frequencies within populations. Here, we address the compelling, but poorly tested, hypothesis that the sex ratio bias caused by such elements profoundly alters their host's mating system. We compare aspects of female and male reproductive biology between island populations of the butterfly Hypolimnas bolina that show varying degrees of female bias, because of a male-killing Wolbachia infection. Contrary to expectation, female bias leads to an increase in female mating frequency, up to a point where male mating capacity becomes limiting. We show that increased female mating frequency can be explained as a facultative response to the depleted male mating resources in female biased populations. In other words, this system is one where male-killing bacteria trigger a vicious circle of increasing male fatigue and female promiscuity. PMID- 17276922 TI - Intrinsic control of precise dendritic targeting by an ensemble of transcription factors. AB - Proper information processing in neural circuits requires establishment of specific connections between pre- and postsynaptic neurons. Targeting specificity of neurons is instructed by cell-surface receptors on the growth cones of axons and dendrites, which confer responses to external guidance cues. Expression of cell-surface receptors is in turn regulated by neuron-intrinsic transcriptional programs. In the Drosophila olfactory system, each projection neuron (PN) achieves precise dendritic targeting to one of 50 glomeruli in the antennal lobe. PN dendritic targeting is specified by lineage and birth order , and their initial targeting occurs prior to contact with axons of their presynaptic partners, olfactory receptor neurons. We search for transcription factors (TFs) that control PN-intrinsic mechanisms of dendritic targeting. We previously identified two POU-domain TFs, acj6 and drifter, as essential players. After testing 13 additional candidates, we identified four TFs (LIM-homeodomain TFs islet and lim1, the homeodomain TF cut, and the zinc-finger TF squeeze) and the LIM cofactor Chip that are required for PN dendritic targeting. These results begin to provide insights into the global strategy of how an ensemble of TFs regulates wiring specificity of a large number of neurons constituting a neural circuit. PMID- 17276923 TI - AKT-1 regulates DNA-damage-induced germline apoptosis in C. elegans. AB - The cellular response to genotoxic stress involves the integration of multiple prosurvival and proapoptotic signals that dictate whether a cell lives or dies. In mammals, AKT/PKB regulates cell survival by modulating the activity of several apoptotic proteins, including p53. In Caenorhabditis elegans, akt-1 and akt-2 regulate development in response to environmental cues by controlling the FOXO transcription factor daf-16, but the role of these genes in regulating p53 dependent apoptosis is not known. In this study, we show that akt-1 and akt-2 negatively regulate DNA-damage-induced apoptosis in the C. elegans germline. The antiapoptotic activity of akt-1 is independent of its target gene daf-16 but dependent on cep-1/p53. Although only akt-1 regulates the apoptotic activity of cep-1, both akt-1 and akt-2 modulate the intensity of the apoptotic response independently of the transcriptional activity of CEP-1. Finally, we show that AKT 1 regulates apoptosis but not cell-cycle progression downstream of the HUS-1/MRT 2 branch of the DNA damage checkpoint. PMID- 17276924 TI - Bilateral inferior petrosal sinus sampling in the management of ACTH-dependent Cushing's syndrome. PMID- 17276925 TI - Apoptosis-related markers for predicting progression of prostate cancer. PMID- 17276926 TI - Assessment of bilateral inferior petrosal sinus sampling (BIPSS) in the diagnosis of Cushing's disease. AB - BACKGROUND: The differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS) remains a challenging issue for clinical endocrinologists. In this respect, bilateral inferior petrosal sinus sampling (BIPSS) appears to be the most sensitive and specific test. Here, we report our 15-year experience of analyzing the performance of BIPSS, both in the correct diagnosis and in the precise lateralization of tumors in patients with Cushing's disease (CD). METHODS: Between 1992 and 2006, 18 patients with CD (16 females, 2 males; age range, 14-56 years) were admitted to Taipei Veterans General Hospital and subjected to BIPSS plus ovine corticotropin-releasing hormone (oCRH) stimulation. Four of them had previously undergone transsphenoidal hypophysectomy (TSH) and had a recurrence thereafter. BIPSS was performed by inserting a catheter in the right and left inferior petrosal sinus for ACTH assay via a femoral vein puncture. An inferior petrosal sinus/peripheral ACTH ratio (C/P ratio) > or = 2 at baseline > or = 3 after oCRH injection indicated a pituitary origin of ACTH secretion, and an interpetrosal ACTH gradient (IPS ratio) > or = 1.4 at baseline or after oCRH indicated evidence of lateralization. RESULTS: Positive BIPSS results were found in 16 patients at baseline and in 17 patients after oCRH injection. In 17 out of 18 patients, TSH was subsequently carried out and a pituitary source was confirmed on histopathologic examination. The only 1 false-negative test result was noted in a patient who had undergone previous TSH. Thus, the sensitivities of BIPSS for the diagnosis of CD before and after oCRH stimulation were 89% and 94%, respectively. Moreover, using an IPS ratio > or = 1.4 as a criterion, BIPSS correctly lateralized the tumor in 9 of 17 and 10 of 17 patients at baseline and after oCRH stimulation, respectively, including in 2 patients who had a centrally located tumor and who had an IPS ratio < 1.4. Thus, the sensitivities of lateralization of BIPSS were 53% and 59%, respectively. None of the 4 patients who had previous TSH were precisely localized by BIPSS. If these 4 patients were excluded, the sensitivities of BIPSS for localizing in the patients who had not undergone previous operation increased to 70% (9/13) at baseline and 77% (10/13) after oCRH stimulation, respectively. CONCLUSION: BIPSS combined with oCRH stimulation is a safe and reliable examination both in the differential diagnosis of CD and in the correct lateralization of pituitary microadenoma in patients without previous pituitary surgery. Nevertheless, this procedure may provide misleading results in patients who have received previous pituitary surgery. PMID- 17276928 TI - Role of hepatic nitric oxide synthases in rats with thioacetamide-induced acute liver failure and encephalopathy. AB - BACKGROUND: Hepatic encephalopathy is neuropsychiatric derangement secondary to hepatic decompensation or portal-systemic shunting. Nitric oxide (NO) synthase inhibition aggravates encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure, suggesting a protective role of NO. This study investigated the roles of endothelium-derived constitutive NO synthase (eNOS) and inducible NOS (iNOS) in the liver of rats with fulminant hepatic failure and encephalopathy. METHODS: Male Sprague-Dawley rats (300-350 g) were randomized to receive TAA 350 mg/kg/day, by intraperitoneal injection or normal saline for 3 days. Severity of encephalopathy was assessed with the Opto Varimex animal activity meter. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin were measured. Hepatic iNOS and eNOS RNA and protein expressions were assessed by reverse transcription-polymerase chain reaction and Western blot analyses, respectively. RESULTS: The TAA group showed lower motor activity counts than the normal saline group. Hepatic eNOS, but not iNOS, mRNA and protein expressions were enhanced in the TAA group. In addition, hepatic eNOS mRNA expression was negatively correlated with total movement but positively correlated with ALT and AST. Protein expression of hepatic eNOS was positively correlated with ALT, AST and bilirubin. CONCLUSION: Upregulation of hepatic eNOS was observed in rats with TAA-induced fulminant hepatic failure and encephalopathy, which might play a regulatory role. PMID- 17276927 TI - Role of p21(WAF1) and p27(KIP1) in predicting biochemical recurrence for organ confined prostate adenocarcinoma. AB - BACKGROUND: Both p21(WAF1) and p27(KIP1) have been reported as prognostic markers predicting biochemical failure for prostate cancers. We examined the expression and prognostic significance of p21(WAF1) and p27(KIP1) in organ-confined (pT2) prostate cancer patients. METHODS: The medical records of 53 pT2 prostate adenocarcinomas were analyzed retrospectively. Radical prostatectomy specimens were stained using anti-p21(WAF1) and anti-p27(KIP1) antibodies. Biochemical relapse was defined as 2 consecutive elevations in serum prostate specific antigen (PSA) level > 0.2 ng/mL with an interval of more than 3 months. The prognostic significance of p21(WAF1) and p27(KIP1) expression was assessed. RESULTS: p21WAF1 immunoreactivity was found in 19 patients (35.8%). Twenty-nine tumors (54.7%) had decreased p27(KIP1) expression. Both markers were not associated with Gleason scores (p = 1.00 for both). At a median follow-up of 49 months, 15 patients (28.3%) experienced biochemical recurrence. Both p21 and p27 had no prognostic significance in log-rank test (p = 0.98 and p = 0.64, respectively). CONCLUSION: p21(WAF1) and p27(KIP1) expression have no role in predicting biochemical relapse for stage pT2 prostate cancers. PMID- 17276929 TI - Toward a better understanding of sinonasal mucosal melanoma: clinical review of 23 cases. AB - BACKGROUND: Primary sinonasal mucosal melanoma is a rare disease, occurring far less often than cutaneous lesions. The objective of this study was to review the records of patients diagnosed with primary sinonasal mucosal melanoma. METHODS: We performed a retrospective review of the medical records of 23 patients with sinonasal mucosal melanoma who were treated at Taipei Veterans General Hospital between 1982 and 2002. RESULTS: Sixteen of the 23 patients were male and 7 were female; their mean age was 68.2 years (range, 39-87 years). At diagnosis, the melanoma was limited to lesions located in the sinonasal area in 20 patients, and had spread in 3 patients. Local recurrence developed in 9 patients, neck metastasis in 5, and distant metastasis in 19. The 5-year disease-specific survival and local control rates were 22.26% and 52.30%, respectively. CONCLUSION: In our experience, primary sinonasal mucosa melanoma is prone to spread from the site of origin. The major obstacle in improving overall survival is achieving systemic control. PMID- 17276930 TI - An adult with aortic arch interruption associated with sinus venosus atrial septal defect and partial anomalous pulmonary venous connection. AB - Interruption of the aortic arch is a rare and usually lethal congenital anomaly that is often associated with multiple cardiac malformations. Most neonates with aortic arch interruption perish once the ductus arteriosus closes after birth. However, sporadic cases have been reported to survive into adulthood uneventfully. Here, we report a 19-year-old male with a 3-month history of exertional dyspnea. A series of cardiovascular studies confirmed the presence of aortic arch interruption in conjunction with sinus venosus atrial septal defect and partial anomalous pulmonary venous connection. To the best of our knowledge, such an association has not been previously reported in adults. PMID- 17276931 TI - Villous adenoma of the ureter with manifestation of mucus hydroureteronephrosis. AB - Ureteral tumor is prone to result in lumen obstruction. Villous adenoma is most frequently found in the colon and rectum, seldom in the urinary tract and even more rarely in the ureter or pelvis. Herein, we present a case of bilateral renal stones of more than 10 years' duration with the chief complaint of right flank pain. Obstruction of the right upper ureter with hydroureteronephrosis was observed on sonography, computed tomography and retrograde pyelography. Ureteroscopy revealed papillary tumor obstructing the upper third of the ureter and inducing hydroureteronephrosis with abundant mucoid content. The ureteral tumor proved to be villous adenoma by pathologic examination. It should be noted that ureteral villous adenoma may be related to previous enteric-type metaplastic mucosa or ureteritis glandularis, demonstrates profuse production of mucus, and may eventually undergo malignant transformation. PMID- 17276932 TI - Management of transorbital brain injury. AB - Transorbital brain injuries caused by metal bar penetration are uncommon and often cause serious damage without prompt treatment. Artifacts caused by the penetrating metal bar on computed tomography (CT) often obscure the actual brain damage along the path of penetration, and delayed treatment for the brain insult may result. We present 2 cases of transorbital brain injury following penetration by a metal bar. CT scans were initially performed on both patients. However, image resolution was poor and the extent of brain damage could not be ascertained due to severe artifacts associated with the metal bars. Both patients deteriorated in the emergency room and subsequently received surgical intervention. One patient recovered uneventfully. Unfortunately, the other patient died following surgery due to an unrecognized intracranial hemorrhage with brain herniation. Based on this experience, we recommend prompt surgical decompression with early CT follow-up to determine the true extent of brain damage and assess for possible delayed events inpatients with extended transorbital brain injuries caused by metal bars. PMID- 17276934 TI - Closed-tube SNP genotyping without labeled probes/a comparison between unlabeled probe and amplicon melting. AB - Two methods for closed-tube single nucleotide polymorphism (SNP) genotyping without labeled probes have become available: unlabeled probe and amplicon melting. Unlabeled probe and amplicon melting assays were compared using 5 SNPs: human platelet antigens 1, 2, 5, and 15 and a C>T variant located 13910 base pairs (bp) upstream of the lactase gene. LCGreen Plus (Idaho Technology, Salt Lake City, UT) was used as the saturating DNA dye. Unlabeled probe data were readily interpretable and accurate for all amplicon lengths tested. Five targets that ranged in size from 42 to 72 bp were well resolved by amplicon melting on the LightScanner (Idaho Technology) or LightTyper (Roche, Indianapolis, IN) with no errors in genotyping. However, when larger amplicons (206 bp) were used and analyzed on lower resolution instruments (LightTyper and I-Cycler, Bio-Rad, Hercules, CA), the accuracy of amplicon genotyping was only 73% to 77%. When 2 temperature standards were used to bracket the amplicon of interest, the accuracy of amplicon genotyping of SNPs was increased to 100% (LightTyper) and 88% (I Cycler). PMID- 17276933 TI - Low frequency of promoter methylation of O6-methylguanine DNA methyltransferase and hMLH1 in ulcerative colitis-associated tumors: comparison with sporadic colonic tumors. AB - To cast light on the contribution of methylation to genesis of ulcerative colitis (UC)-associated tumors, promoter methylation and expression of O6-methylguanine DNA methyltransferase (MGMT), hMLH1, p16INK4, and E-cadherin were examined in 14 low-grade dysplasias (LGDs), 15 high-grade dysplasias (HGDs), and 14 adenocarcinomas associated with UC and, for comparison, in 30 sporadic adenomas with LGD, 30 adenomas with HGD, and 60 adenocarcinomas, using methylation specific polymerase chain reaction and immunohistochemical analysis. The frequency of MGMT and hMLH1 methylation in UC-associated tumors was low, with a significant difference between HGD and sporadic adenomas with HGD of the left hemicolon. The methylation frequency of p16INK4 in UC-associated tumors was also relatively low compared with sporadic colonic tumors. For E-cadherin, methylation was limited in both types of tumor. Decrease of expression of MGMT, hMLH1, and p16INK4 was significantly correlated with methylation. Thus, compared with the sporadic type, contribution of methylation to UC-associated tumorigenesis seems to be low. PMID- 17276935 TI - A Review of beta2 -glycoprotein-l antibody testing results from a peer-driven multilaboratory quality assurance program. AB - We evaluated the results of lgG beta2-glycoprotein-I (B2GPI) antibody assays in a multilaboratory setting by analyzing data from an external quality assurance program for the 2003 through 2005 cycles for 27 serum samples, including quantitative IgG-B2GPI values and qualitative interpretation and grading (ie, negative or positive; grade of positivity), according to method type and in conjunction with clinical data. We report high interlaboratory variation in numeric IgG-B2GPI results, comparable to that reported for IgG anticardiolipin antibody (aCL) testing, and some method-based variation. For example, interlaboratory coefficients of variation for IgG-B2GPI were more than 50% in 19 samples (70%). For qualitative reporting, there was generally better consensus than previously reported for semiquantitative IgG-aCL testing; although 100% consensus occurred for only 11 samples (41%), more than 90% of laboratories agreed for 19 samples (70%). In some cases, laboratory findings (negative or positive IgG-B2GPI) did not agree with clinical information. Despite the lack of formal standardization for IgG-B2GPI testing compared with IgG-aCL, there seems to be better cross-laboratory consensus. Improvement in standardization of these assays is still required to improve interlaboratory and intermethod concordance of results and interpretation between laboratories and the clinical usefulness of IgG-B2GPI testing. PMID- 17276936 TI - Host-dependent patterns of tissue injury in invasive pulmonary aspergillosis. AB - Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in neutropenic, nonneutropenic, and other immunocompromised patients. We therefore compared the patterns of infection and inflammation among 3 cohorts of immunocompromised patients with profound neutropenia, nonneutropenic immunosuppression, and hematopoietic stem cell transplantation. Lesions of IPA in neutropenic patients and hematopoietic stem cell transplant (HSCT) recipients were similar and consisted predominantly of angioinvasion and intraalveolar hemorrhage. The frequency of these histologic findings in neutropenic patients and HSCT recipients differed significantly from those of nonneutropenic patients (P < .05). It is noteworthy that even if HSCT recipients have normal peripheral blood neutrophil counts, there may be no influx into sites of infection. In the nonneutropenic cohort, lesions of IPA consisted mainly of neutrophilic and monocytic infiltrates and inflammatory necrosis. Thus, the status of innate host defenses contributes significantly to the histologic patterns observed in IPA. PMID- 17276937 TI - Mediastinal adenopathy, lung infiltrates, and hemophagocytosis: unusual manifestation of pediatric anaplastic large cell lymphoma: report of two cases. AB - To date, only 1 report describes an anaplastic large cell lymphoma (ALCL) associated with hemophagocytosis in the pediatric population. To better characterize this unusual manifestation of ALCL, we identified 2 additional cases. Both patients had fever, cytopenia, decreased fibrinogen level, mediastinal or hilar adenopathy, minimal to no peripheral adenopathy, and lung infiltrates. Bone marrow biopsies and aspirates revealed striking hemophagocytosis but no ALCL. One patient fulfilled the criteria for hemophagocytic syndrome, but the other lacked 1 criterion. Both patients were initially given a misdiagnosis of infection-associated hemophagocytosis. Definitive diagnosis required lymph node biopsies that showed CD30+, anaplastic lymphoma kinase-l+ ALCL. Both tumors responded to standard lymphoma chemotherapy. One patient achieved complete remission, whereas the other patient died of complications after 2 cycles of therapy. These findings are similar to the first reported case and indicate that pediatric ALCL can manifest with an unusual constellation of symptoms consisting of hemophagocytosis, mediastinal or hilar adenopathy, and lung infiltrates. PMID- 17276938 TI - Examination of platelet function in whole blood under dynamic flow conditions with the cone and plate(let) analyzer: effect of erythrocytosis and thrombocytosis. AB - We studied cone and plate(let) analysis (CPA) for evaluating global platelet function in whole blood under arterial flow conditions (approximately 1,800 seconds(-1)). CPA allows direct visualization and quantitation of platelet adhesion (surface coverage [SC]) and determination of average aggregate size (AS) following brief shearing of a small blood sample (3.2% sodium citrate) in plastic wells. By using blood from healthy volunteers manipulated to alter platelet or RBC counts and blood from patients with myeloproliferative disorders (MPDs), quantitative and qualitative changes in SC and AS were observed. Thrombocytosis resulted in increased SC, whereas erythrocytosis increased AS. The RBC volume (mean corpuscular volume) had no effect. It is interesting that differences in CPA AS were discerned among subgroups of patients with MPD undergoing different treatment regimens. These studies suggest that CPA platelet deposition patterns may provide novel insight into global platelet function during hemodynamic flow. PMID- 17276939 TI - Comparison of apolipoprotein B and non-high-density lipoprotein cholesterol for identifying coronary artery disease risk based on receiver operating curve analysis. AB - Whether or non-high-density lipoprotein cholesterol is equivalent to apolipoprotein B (apo B) for screening remains controversial. One reason for continued controversy is that most studies express results as relative risk/hazard or odds ratios based on P values that reflect diagnostic values poorly. Apo B and lipoprotein lipids were compared in 437 men. The results were evaluated by multivariate techniques and by receiver operating characteristic (ROC) curves. When analyzed by ROC curves, the difference between Apo B and lipoprotein lipids proved to be less than would be anticipated from the odds ratios. Although, after adjustment, the difference was about 14% by odds ratios, ROC analysis showed only a small difference of about 1%. These data show that clinical studies should analyze the data using an absolute measure of risk such as ROC curves rather than just relative indexes. Such a small absolute difference may also explain discrepancies between studies. PMID- 17276940 TI - Expression of p63 in thymomas and normal thymus. AB - The p63 gene, a member of the p53 family, is an epithelial marker expressed in embryonic ectoderm, breast myoepithelium, prostate, oral epithelium, epidermis, and urothelium. The DeltaN-p63 isoforms of p63, which are believed to behave as oncogenes, are expressed in squamous cell carcinoma, basal cell carcinoma, and transitional cell carcinoma. Only a few authors have looked for p63 expression in thymomas and normal thymus. We, therefore, thought of undergoing such a search by taking advantage of our archival material. We studied 66 cases of thymoma (1 type A, 8 type AB, 12 type B1, 19 type B2, 12 type B3, and 14 type C/thymic carcinoma) and 10 specimens of normal human thymus arranged in tissue microarrays. All thymomas (including thymic carcinomas) were positive for p63 regardless of type. Most of the epithelial cells of the normal thymus were also positive for this marker. PMID- 17276941 TI - Chasing colonic "polyps": features that predict underlying adenomas in initially nondiagnostic endoscopic biopsy specimens. AB - Initial tissue sections from biopsies of endoscopically apparent colonic polyps may not always demonstrate a lesion to account for the clinical findings. Studies have shown that deeper sections and/or reorientation reveal lesions in 10% to 31% of initially nondiagnostic cases. However, many are clinically inconsequential hyperplastic or inflammatory polyps, and, thus, exhaustive efforts to identify them may not be justified. The aim of this study was to identify clinical parameters that predict the detection of adenomas in initially nondiagnostic endoscopic biopsies of colonic "polyps." We reoriented, reembedded, and obtained deeper tissue levels on 100 initially nondiagnostic biopsy specimens of clinically apparent polyps and found 9% to contain tubular adenomas. Only 3% of polyps smaller than 5 mm proved to be adenomas, compared with 22% of those 5 mm or larger (P < .01). We conclude that nondiagnostic biopsy specimens of polyps measuring 5 mm or more should be further evaluated because they are more likely to represent adenomas, whereas smaller lesions are usually clinically inconsequential. PMID- 17276942 TI - S100A4 protein and mesothelin expression in dysplasia and carcinoma of the extrahepatic bile duct. AB - We evaluated the expression of S100A4 protein and mesothelin in dysplasia and carcinoma of the extrahepatic bile duct (EBD) and their potential use as adjuncts for differentiating carcinomatous and significant high-grade dysplastic epithelium from reactive or inflammatory glandular atypia of the EBD. We used immunohistochemical analysis on formalin-fixed tissue sections from 10 cases of carcinoma, 6 cases of high-grade dysphasia (HGD), 4 cases of low-grade dysplasia (LGD), and 10 cases of benign or reactive or inflammatory epithelium from the EBD. Expression of S100A4 protein was observed in 8 invasive carcinomas (80%), 5 HGD/carcinoma in situ cases (83%), and 0 LGDs. Mesothelin was expressed in 5 (50%) of 10 adenocarcinomas, 1 (17%) of 6 HGD/adenocarcinoma in situ cases, and 0 LGDs. No case of normal or reactive epithelium was positive for S100A4 protein or mesothelin. Mesothelin has moderate sensitivity and high specificity, whereas S100A4 protein is sensitive and specific for the identification of carcinoma and HGD of the EBD. S100A4 protein alone or combined with mesothelin can be used as an adjunct in differentiating carcinomatous and significant high-grade dysplastic epithelium from LGD and reactive or inflammatory glandular atypia of the EBD. PMID- 17276943 TI - Usefulness of optical density values from heparin-platelet factor 4 antibody testing and probability scoring models to diagnose heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia (HIT) is a complication caused by antibodies directed to the heparin-platelet factor 4 (PF4) complex with a seemingly paradoxical high risk of thrombosis. Discontinuation of heparin and administration of an alternative anticoagulant is important in prevention of catastrophic thrombosis. Diagnosis is challenging and based on clinical probability models (Warkentin 4 Ts and Chong scale) and, to a lesser degree, laboratory testing. Enzyme-linked immunosorbent assay (ELISA) measurement of heparin-PF4 antibodies is commonly used but has low predictive values for thrombosis. We analyzed 105 cases of suspected HIT and compared optical density values and the Warkentin 4 Ts for sensitivity, specificity, positive predictive value, and negative predictive value (NPV). The predictive value of ELISA alone was inferior to the Warkentin 4 Ts score. The sensitivity and NPV of the clinical score was improved by incorporating ELISA results. The combination of a negative ELISA result with low probability 4 Ts resulted in an NPV of 94%. PMID- 17276944 TI - Mitotic rate in melanoma: a reexamination. AB - We reexamined the relationship between mitotic rate and overall survival in more than 1,200 cases of cutaneous melanoma with long-term follow-up. Like others, we found that mitotic rate was significantly associated with survival (P < 4 x 10( 8)) and more prognostic than tumor ulceration but was not an independent prognosticator because it was significantly associated with tumor thickness and ulceration. Thus, all 3 histologic variables are interrelated; among these, tumor thickness is the most important. Although mitotic rate can be effectively categorized in 3 groups (1/mm2, 1/mm2(-4)/mm2, and > 4/mm2), the optimal way to use mitotic rate remains unclear, and even this simplification requires determining the raw number per square millimeter. Because the collective information provided by tumor thickness, mitotic rate, ulceration, patient age, and site of tumor about hard outcomes such as 5-year fatality is limited and because measuring mitotic rate requires extra time, we recommend that mitotic rate need not be part of routine reports on cutaneous melanoma. Nevertheless, mitotic rate should continued to be measured in academic centers and other sites that maintain large prospective databases on melanoma, and it should be included in further studies of prognosis and adjuvant therapies for cutaneous melanoma. PMID- 17276945 TI - Performance characteristics of five automated CA 19-9 assays. AB - Serum concentrations of cancer antigen (CA) 19-9 can be useful in monitoring response to therapy in pancreatic cancer. The objective of this study was to evaluate 5 automated CA 19-9 assays: ARCHITECT 12000 (Abbott Diagnostics, Abbott Park, IL), ADVIA Centaur (Bayer Diagnostics, Tarrytown, NY), UniCel Dxl 800 (Beckman Coulter, Fullerton, CA), IMMULITE 2000 (Diagnostic Products, Los Angeles, CA), and Elecsys E170 (Roche Diagnostics, Indianapolis, IN). All methods were evaluated for limit of detection, linearity, imprecision, method comparison, and reference intervals. Limit of detection results were all below 2.0 kU/L and met the manufacturers' claims. Linearity had deviation from target values that ranged from 4.5% to 26.7%. All methods showed acceptable imprecision with total coefficients of variation less than 8%. Method comparison by Passing-Bablok analysis resulted in slopes ranging from 1.00 to 2.06 and correlation coefficients of 0.85 to 0.98. Between 97.6% and 99.2% of results from healthy volunteers were less than 35 kU/L. All methods show acceptable analytic performance. PMID- 17276946 TI - Castleman disease of the hyaline-vascular type confined to the kidney. AB - The case is a 38-year-old man in whom a solitary subcapsular left renal cortical mass was successfully resected. Comorbidities included a benign epididymal cyst and a history of nephrolithiasis. Computed tomographic imaging demonstrated a 1.8 cm enhancing mass in the anterior midregion of the kidney. An open partial nephrectomy was performed, and histopathologic examination established a diagnosis of the hyaline-vascular type of Castleman disease (CD). The patient had an uneventful postoperative course and has experienced no local or metastatic recurrence in the 10 months since surgery. CD localized in the kidney is an exceptionally rare occurrence but should be included in the complete differential diagnosis of solitary renal cortical mass lesions. PMID- 17276947 TI - The expanded use of HPV testing in gynecologic practice per ASCCP-guided management requires the use of well-validated assays. PMID- 17276948 TI - Diagnosis of metastatic melanoma by fine-needle biopsy: analysis of 2,204 cases. AB - Fine-needle biopsy (FNB) has been reported as a rapid, minimally invasive technique for the diagnosis of metastatic melanoma. The diagnostic accuracy of FNB was assessed in a consecutive series of 2,204 FNBs of clinically suspicious lesions from patients with previous primary melanomas treated at the Sydney Melanoma Unit, Sydney, Australia, between January 1992 and December 2002. The sensitivity and specificity of FNB were 96.3% and 98.9%, respectively. There were 5 false-positive cases (0.6%), which were verified as metastatic adenocarcinoma (3 cases) or reactive processes (organizing hematoma and chronic osteomyelitis, 1 each). False-negative diagnoses (6.7% of cases) were associated with a variety of clinicopathologic factors, including difficult-to-access anatomic sites (eg, high axilla or deep inguinal), small lesions, and lesional characteristics such asfibrosis, necrosis, or cystic change. FNB is a highly accurate, rapid, and cost effective procedure for the diagnosis of metastatic melanoma and should be considered as the initial diagnostic procedure of choice in patients with melanoma with clinically suspected metastases. PMID- 17276949 TI - Histologic criteria for adrenocortical proliferative lesions: value of mitotic figure variability. AB - This study compared 3 systems and a newly designed stepwise discriminant diagnostic system (SDDS) to assess accuracy, reproducibility, and reliability in adrenocortical nodular hyperplasia (ACNH; n = 82), adenoma (ACA; n = 78), and carcinoma (ACC; n = 32) (diagnoses according to World Health Organization criteria; median follow-up, 135 months). In cross-validations, we studied cortex appearance, growth pattern, cytoplasmic features, nuclear parameters, mitotic figure counting (MFC), necrosis, invasion, and stromal-inflammatory reactions. The SDDS independent predictors were MFC/high-power field SD, anisokaryosis, cortex appearance, and stromal reaction, correctly classifying 100% of ACNH, 91% of ACA, and 88% of ACC cases. The Hough system correctly classified 78% of ACNH, 81% of ACA, and 84% of ACC cases; the Weiss and van Slooten systems correctly classified 100% of ACNH, 0% of ACA, and 92% of ACC cases. MFC variability is the most important adrenocortical malignancy criterion. Accurate malignancy diagnosis requires multiple variable evaluations, provided by SDDS (the most specific system) and the Weiss or van Slooten system (the most sensitive). SDDS is the most useful system for distinguishing tumors from ACNH (myxoid stroma and anisokaryosis). PMID- 17276950 TI - Comparison of evaluations for hormone receptors in breast carcinoma using two manual and three automated immunohistochemical assays. AB - The aims of this study were to compare the quality of immunohistochemical assays of estrogen receptor (ER) and progesterone receptor (PR) and to compare the intermethod variability of assays from different manufacturers. immunohistochemical staining was entrusted to the following laboratories in Japan: Kyowa Medex, dealing with the products of BioGenex (Mishima, Shizuoka), DAKO Japan (Kyoto) and Ventana Japan (Yokohama). All slides were semiquantitatively evaluated according to the Allred score. Intermethod variability showed fair to moderate multirater kappa values for ER and PR (for total score, ER, kappa = 0.34; PR, kappa = 0.45). Another scoring system was also applied in which, irrespective of the intensity of nuclear staining, the proportion of cells stained in each specimen was recorded as 0; less than 1%; 1% or more and less than 10%; or 10% or more. Intermethod variability showed substantial multirater kappa values for ER and PR (according to percentage of positive cells, ER, kappa = 0.67; PR, kappa = 0.72). Concerning intermethod consistency, the scoring system based on the percentage of positive cells was advantageous over other scoring systems. PMID- 17276951 TI - The dilution of benzalkonium chloride (BAK) in the tear film. AB - The claim that benzalkonium chloride (BAK) synergistically enhances the antibiotic efficacy of gatifloxacin ophthalmic solution 0.3% (preserved with 0.005% BAK [50 microg/mL), Zymar; Allergan Inc., Irvine, Calif, USA) has been the subject of several studies. The purpose of this prospective clinical study was to test the hypothesis that BAK would be significantly diluted shortly after topical ocular administration and would thereafter have little or no effect on the enhancement of the antibiotic efficacy of commercial gatifloxacin on the ocular surface. This hypothesis was tested by investigators who measured the concentration of tear film BAK at successive time points after topical administration of commercial gatifloxacin. After subjects (N=10) received 5 separate instillations of a single 35-microL drop of gatifloxacin 0.3% ophthalmic solution in each eye, tear samples were collected at 30 sec, 1 min, 3 min, 5 min, and 20 min, with the use of graduated 5-microL glass microcapillaries. A validated high-performance liquid chromatography method was used to measure the concentration of BAK in each tear sample. The results showed rapid BAK dilution to 6.4 microg/mL, 3.2 microg/mL, 1.4 microg/mL, below the detection limit, and below the detection limit at 30 sec, 1 min, 3 min, 5 min, and 20 min after instillation of a single 35-microL drop of gatifloxacin. Because such rapid dilution reduces the concentration of BAK to near zero in minutes and does not allow the time (1 h) required for effective bacterial kill power, BAK is not expected to have a clinically significant effect on enhancement of the antimicrobial efficacy of gatifloxacin on the human ocular surface. PMID- 17276952 TI - Effects of alendronate and risedronate on bone mineral density and bone turnover markers in late postmenopausal women with osteoporosis. AB - This study was undertaken to compare the effects of alendronate and risedronate on bone mineral density (BMD) and bone turnover markers (BTMs) in late postmenopausal women with osteoporosis. Thirty women older than 60 y of age were randomly assigned to receive alendronate 10 mg (n=16) or risedronate 5 mg (n=14) on a daily basis. The patients were followed every 3 mo for 12 mo. BMD measurements were taken at baseline and at the end of the study, and BTMs were measured at 3-mo intervals. By the end of the study, there were statistically significant increases in BMD in both groups at all sites at which they were measured (P<.001). However, these differences were not statistically significant between groups. By the end of the study, all BTMs had decreased significantly and to a similar extent in both groups. The most significant change was observed in the third month of the study. A negative correlation was noted between percentage change in bonespecific alkaline phosphatase and femoral neck BMD (r=-0.467). This study reported no difference between the 2 drugs in their effects on BMD and BTMs. PMID- 17276953 TI - Holter monitoring for 24 hours in patients with thromboembolic stroke and sinus rhythm diagnosed in the emergency department. AB - It is well known that patients with ischemic stroke show ST-T abnormalities and various rhythm abnormalities on an electrocardiogram (ECG). The most commonly encountered rhythm abnormality is atrial fibrillation. It was recently shown that paroxysmal atrial fibrillation (PAF) is an important causative factor in patients with stroke. Detection of PAF is important in identifying the cause, prognosis, and treatment in patients with thromboembolic stroke. Investigators in the present study followed patients with thromboembolic stroke who had been admitted to the emergency department in sinus rhythm; 24-h Holter monitoring was used, and patients were assessed at referral and every 6 h for 24 h with ECG, which was used to detect rhythm disturbances, especially PAF. In 26 patients with stroke who came to the emergency department, acute thromboembolic stroke was diagnosed on the basis of magnetic resonance imaging; no rhythm abnormalities were noted on Holter monitoring. Eighteen patients were male and 8 were female (mean age: 66+/ 13 y). Arrhythmia was identified on ECG in 3 patients (11%) and on 24-h Holter monitoring in 24 patients (92%). PAF was diagnosed in 3 patients (11%) on ECG and in 11 patients (42%) on Holter monitoring. In 2 patients, nonsustained ventricular tachycardia was detected only on Holter monitoring, which was found to be significantly superior to ECG for the detection of arrhythmias (P<.001). Investigators found no significant relationship between PAF and variables such as hypertension, diabetes, coronary artery disease, history of myocardial infarction, ST-T changes, and elevations in cardiac markers. However, a significant relationship (P<.01) was seen between nonsustained ventricular tachycardia and a history of myocardial infarction. No relationship was discerned between arrhythmia and stroke localization. Study results suggested that (1) PAF is a commonly diagnosed rhythm abnormality, and (2) Holter monitoring is superior to routine ECG for the detection of arrhythmias such as PAF in patients anticipated to have thromboembolic stroke with sinus rhythm. PMID- 17276954 TI - Enhancement of ultrasound contrast agent in high-intensity focused ultrasound ablation. AB - High-intensity focused ultrasound (HIFU) is becoming an increasingly attractive modality for ablation. Enhancement of HIFU is an important issue that has been discussed and investigated worldwide. Ultrasound contrast agents are considered to constitute an efficient medium for changing acoustic characteristics and improving energy deposition in the focal region. The role of microbubbles in inducing enhanced heating, cavitation, and other related events in HIFU ablation has been investigated, with the goal of improving coagulation necrosis volume or decreasing acoustic power and exposure duration. Consequently, with the use of ultrasound contrast agents, applications of HIFU are expected to become more efficient, safe, and accurate and to produce fewer adverse effects. This paper reviews studies that have been conducted to investigate the enhancement of ultrasound contrast agents in HIFU ablation through experiments that were carried out in vitro and in vivo; an analysis of results of this enhancement mechanism is provided. PMID- 17276955 TI - Comparison of simultaneous antegrade/vein graft cardioplegia with antegrade cardioplegia for myocardial protection. AB - Antegrade cardioplegic delivery via the aorta ensures distribution of cardioplegic solution through open arteries, but distribution may not be adequate beyond a stenotic coronary artery. This potential problem can be overcome by direct delivery of cardioplegia via a vein graft. The purpose of this study was to compare simultaneous antegrade/vein graft cardioplegia with antegrade cardioplegia during coronary artery bypass surgery. Twenty patients were divided into 2 groups. In group 1, intermittent antegrade cardioplegia was provided (n=10). In group 2, intermittent antegrade cardioplegia was supplemented by antegrade perfusion of vein grafts after distal anastomoses were completed (n=10). Data on enzyme release and hemodynamics were obtained preoperatively, before the induction of anesthesia, just before cross-clamping, immediately after aortic unclamping, and at 1, 6, 12, 24, and 48 h after unclamping. Enzyme release (creatinine phosphokinase-isoenzyme MB, cardiac troponin I, myoglobin) was similar in both groups (P>.05). Furthermore, no significant difference was noted in the incidence of postoperative low cardiac output syndrome, perioperative myocardial infarction, or ventricular arrhythmia (P>.05). In conclusion, both techniques permitted rapid postoperative recovery of myocardial function. Supplementation of antegrade perfusion of vein grafts with antegrade cold blood cardioplegia offered no advantage to study patients.However, hemostasis of a distal anastomosis may be controlled by this technique. PMID- 17276956 TI - The effectiveness of various doses of octreotide for sulfonylurea-induced hypoglycemia after overdose. AB - This study was conducted to investigate the effectiveness of various doses of octreotide in reducing hypoglycemic attacks and the need for dextrose in patients with refractory and recurrent hypoglycemia related to sulfonylurea toxicity. This study was carried out at the Center of Experimental Research of Selcuk University Meram School of Medicine in Konya, Turkey. A total of 40 New Zealand rabbits of both sexes, weighing between 2500 and 3000 g, were used in this experiment. Rabbits were randomly divided into 4 groups, each of which consisted of 10 animals. All animals were given oral gliclazide 100 mg. For the treatment of hypoglycemic attacks in group I, only 15 mL of 50% dextrose (7.5 g) was given intravenously; in groups II, III, and IV, octreotide was given in doses of 25 ug, 50 ug, and 100 ug, respectively. Octreotide was given to groups II, III, and IV at the 8th hour (when hypoglycemic attacks were induced), along with an intravenous infusion of an additional 15 mL of 50% dextrose (7.5 g) for each hypoglycemic attack that occurred. After the toxic dose was given, the rabbits were given the amount of dextrose used before and after octreotide administration, and the numbers of hypoglycemic attacks were recorded. The values of blood glucose for all animals were read every hour on the hour from the beginning of the study, and the study ended at the 24th hour, when hypoglycemic attacks stopped. A significant difference was observed between groups I, II, and IV in numbers of hypoglycemic attacks that occurred and dextrose doses given between 9 and 24 h (P=.001). The findings of this study suggest that a single dose of octreotide 100 ug may be used to reduce the number of refractory and recurrent hypoglycemic attacks that occur because of sulfonylurea overdose; large prospective studies are needed to validate these findings. PMID- 17276957 TI - Determination of risk factors for hypertension through the classification tree method. AB - Most current statistical strategies for determining risk factors for hypertension (HT) among certain populations have proved inconclusive. In this study, the classification tree method, which is more practical and easy to understand than other statistical methods, was used to determine the risk for HT among outpatients in a clinic in Denizli province, western Turkey, between January 2002 and July 2004. The effects of 14 risk factors (body mass index, waist-to-hip ratio, age, serum total cholesterol, serum triglycerides, sex, HT in first-degree relatives, diabetes mellitus, smoking, stress factors, alcohol consumption, dyslipidemia in first-degree relatives, dyslipidemia [previously diagnosed], and saturated fat consumption) on HT were evaluated in this population. In all, 1761 adults at the outpatient clinic were recruited for lipid and HT measurements. The classification tree method revealed 7 main risk factors (body mass index, waist to-hip ratio, sex, serum triglycerides, serum total cholesterol, HT in first degree relatives, and saturated fat consumption) for HT. The findings of the present study suggest that the classification tree is a valuable statistical method for evaluating multiple risk factors for HT. PMID- 17276959 TI - Median and ulnar nerve block for endoscopic carpal tunnel release. AB - A median and ulnar nerve block was administered for endoscopic carpal tunnel release. Three (14.2%) of 21 patients required further anesthesia with local anesthetic agents and sedation. No solution ran back to the surgical site. This technique is rapid and reliable, and it seems to be suitable for outpatient surgery. PMID- 17276958 TI - Circulating complement (C3 and C4) for differentiation of SIRS from sepsis. AB - The systemic inflammatory response of the body to invading microorganisms, called sepsis, leads to profound activation of the complement (C3 and C4) system. The present study was conducted to compare the use of serum C3 and C4 levels with C reactive protein (CRP) and thrombocyte and leukocyte counts in differentiating patients with systemic inflammatory response syndrome (SIRS) from those with sepsis. Over a 6-mo period, all patients with SIRS or sepsis who stayed in the intensive care unit for >24 h were enrolled in the study. At admission, each patient's clinical status was recorded, and blood was taken for laboratory analysis (complete blood count, CRP, C3, and C4). A total of 58 patients with SIRS and 41 patients with sepsis were admitted to the study. The mean+/-SD thrombocyte count was found to be significantly lower in septic patients (179,975+/-95,615) than in those with SIRS (243,165+/-123,706) (P=.005); no difference in plasma concentrations of CRP and levels of C3 and C4 was noted between groups. The thrombocyte count was determined to be the most reliable parameter for differentiating between SIRS and sepsis (highest area under the curve=0.656). PMID- 17276960 TI - Reduction of cardiovascular risk and mortality: a population-based approach. AB - The purpose of this study was to evaluate risk pattern and mortality in a general population epidemiologic study performed by a staff of hypertension specialists working as the "good father of a family," with lifestyle and therapeutic advice and instrumental measurements. Mortality among the study population (n=856) during the 4-y study was compared with that recorded in the general population during the 4-y period before the study; those who refused to participate in the study were also recorded (n=280). Among study subjects, blood pressure decreased by 3.6/3.5 mm Hg (P<.01/P<.0001), serum total cholesterol by 3.8% (P<.0001), and low-density lipoprotein cholesterol by 10.9% (P<.01); awareness of hypertension increased by 87% (P<.0001); 20% of hypercholesterolemic patients (P<.01) and 28% of diabetic patients (P<.001) were identified; and 40% of hypertensive patients (P<.0001) were treated. Overall 4-y mortality was 12.5% in study subjects, 36.6% in renitent subjects (P<.0001 vs enrolled), and 19.9% during the period preceding the study (P<.0001 vs enrolled); cardiovascular mortality rates were 5.8%, 18.6% (P<.0001), and 11.4% (P<.0001), respectively. In particular, the frequency of fatal stroke was 0.06%, 3.8% (P<.0001), and 2.5% (P<.0001), respectively, and that of fatal coronary events was 3.4%, 7.5% (P<.0001), and 4.6% (P<.0001), respectively. In conclusion, when an epidemiologic professional staff member approaches patients in a manner similar to that of the "good father of a family," a better risk pattern and lower mortality rates (particularly cerebrovascular and coronary) are seen in those who are receptive to the care provided; those who decide not to participate in health care opportunities do not benefit. PMID- 17276961 TI - Progression of glaucoma associated with the Sirsasana (headstand) yoga posture. AB - This article reports a case of progressive glaucomatous optic neuropathy and visual field loss that occurred in a patient who practiced the Sirsasana (headstand) yoga posture on a daily basis for many years. Visual field analysis was performed through standard automated perimetry. Intraocular pressure (IOP) was measured through pneumotonometry in the sitting position and in the head-down position. Stereo-optic disc photographs were obtained. IOP increased significantly in the head-down position. Optic disc evaluation revealed a new disc hemorrhage in the left eye. Visual field analysis over a period of 2 y showed progression of a superior arcuate defect in the left eye. Transient increases in IOP associated with the yoga headstand posture may lead to progressive glaucomatous optic nerve damage and visual field loss. PMID- 17276963 TI - Effect of interleukin-5 receptor-alpha short hairpin RNA-expressing vector on bone marrow eosinophilopoiesis in asthmatic mice. AB - Bone marrow eosinophilopoiesis induced by interleukin (IL)-5 is a major contributor to eosinophilic airway inflammation in asthma. However,research on the use of IL-5 receptor alpha (IL-5Ralpha) as the target has seldom been reported. This study was undertaken to explore the effects of inhibition of IL 5Ralpha expression through an IL-5Ralpha short hairpin RNA-expressing vector on bone marrow eosinophilopoiesis and airway inflammation in an asthmatic mouse model. An effective plasmid vector was selected that could express short hairpin RNA targeted at IL-5Ralpha (P-IL-5Ralpha). An adenovirus vector (Ad) was then constructed that was inserted in an effective template sequence (Ad-IL-5Ralpha). An animal model of asthma was established by sensitizing and challenging Balb/c mice with ovalbumin. Animals were treated intravenously with Ad-IL-5Ra and changes in bone marrow eosinophilopoiesis and airway inflammation were detected in asthmatic mice. Investigators found that P-IL-5Ra-3 targeted at the sequence of CAG CTG CCT GGT TCG TCT T markedly suppressed IL-5Ralpha expression in B lymphoma cells in vitro. In addition, Ad-IL-5Ralpha could suppress IL-5Ralpha expression in murine bone marrow cells in vitro and in vivo, and it could significantly decrease IL-5-induced eosinophilia in cultured bone marrow cells. Additional studies indicated that intravenously injected Ad-IL-5Ralpha not only selectively reduced the number of eosinophils in the bone marrow, peripheral blood, and bronchoalveolar lavage fluid, it also relieved airway inflammation in asthmatic mice. Results reported here show that blocking of IL-5Ralpha expression through RNA interference can enhance effective treatment of asthma, and that bone marrow can be used as a key targeted organ in the treatment of asthmatic mice. PMID- 17276962 TI - Effects of tibolone on abdominal subcutaneous fat, serum leptin levels, and anthropometric indices: a 6-month, prospective, randomized, placebo-controlled, double-blind study. AB - This study was undertaken to evaluate the effects of tibolone on abdominal subcutaneous fat, serum leptin levels (SLLs), and anthropometric indices, and to investigate potential relationships between SLLs, subcutaneous abdominal fat thickness, and anthropometric indices in postmenopausal women. In a 6-mo, prospective, randomized, double-blind, placebo-controlled study, 40 healthy postmenopausal women aged 42 to 67 y (mean: 50+/-4.7 y) were randomly assigned to 1 of 2 groups; during a 6-mo treatment period, the first group received tibolone (Livial tablet; Organon, The Netherlands; 2.5 mg/d; n=19) and the other group was given placebo (n=21). Fasting SLLs determined by enzyme-linked immunosorbent assay, subcutaneous abdominal fat thickness assessed by ultrasound, and anthropometric indices of body weight, body mass index, waist and hip circumference, and waist-to-hip ratio (WHR) were recorded at the beginning and the end of the study. Statistical analyses were performed with Mann-Whitney, Wilcoxon, and Spearman tests. P values <.05 were considered significant. No significant differences between the 2 groups were reported in terms of all baseline characteristics. After 6 mo, body weight (+0.77+/-0.43 kg) and SLLs (+14.7+/-6.4 ng/mL) increased in the placebo control group, whereas waist circumference (-2.6+/-3.0 cm), hip circumference (-3.6+/-3.5 cm), and subcutaneous abdominal fat thickness (-4.3+/-4.8 cm) decreased significantly in the tibolone group (P<.05). At the end of the study, group comparisons revealed significant differences in waist and hip circumference and subcutaneous abdominal fat thickness (P<.05). At baseline, SLLs were correlated with subcutaneous abdominal fat thickness and all anthropometric indices except WHR (P<.05). Subcutaneous abdominal fat thickness was also highly correlated with all indices except WHR (P<.0001). Tibolone was found to decrease waist and hip circumference, as well as subcutaneous abdominal fat thickness. Also, tibolone appeared to attenuate weight gain and leptin increase. SLLs and subcutaneous abdominal fat thickness were positively correlated with all anthropometric indices except WHR. PMID- 17276964 TI - Endometrial apoptosis induced by a 900-MHz mobile phone: preventive effects of vitamins E and C. AB - Numerous reports have described the effects induced by an electromagnetic field (EMF) in various cellular systems. The purposes of this study were to examine oxidative stress that promotes production of reactive oxygen species induced by a 900-megahertz (MHz) mobile phone and the possible ameliorating effects of vitamins E and C on endometrial tissue against EMF-induced endometrial impairment and apoptosis in rats. Animals were randomly grouped as follows: (1) sham operated control group (n=8), (2) 900 MHz EMF-exposed group (n=8; 30 min/d for 30 d), and (3) 900 MHz EMF-exposed group, treated with vitamins E and C (n=8; 50 mg/kg intramuscularly and 20 mg/kg body weight intraperitoneally before daily EMF exposure). Malondialdehyde (an index of lipid peroxidation) was used as a marker of oxidative stress-induced endometrial impairment; Bcl-2, Bax, caspase-3, and caspase-8 were assessed immunohistochemically. In this study, increased malondialdehyde levels in endometrial tissue and apoptosis illustrated the role of the oxidative mechanism induced by exposure to a 900-MHz mobile phone-like device and vitamins E and C; via free radical scavenging and antioxidant properties, oxidative tissue injury and apoptosis were ameliorated in rat endometrium. In conclusion, exposure to 900-MHz radiation emitted by mobile phones may cause endometrial apoptosis and oxidative stress, but treatment with vitamins E and C can diminish these changes and may have a beneficial effect in preventing endometrial changes in rats. PMID- 17276965 TI - Comparison of the effectiveness of reboxetine versus fluoxetine in patients with atypical depression: a single-blind, randomized clinical trial. AB - The atypical subtype of depression appears to be well validated and common, and it is unique among Axis I disorders in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) in that it includes a personality trait, rejection sensitivity, as a criterion. Drug selection remains a challenge for the clinician who treats patients with this subtype of depression. Noradrenergic antidepressants have been thought to have prominent effects in improving such symptoms as loss of motivation, drive, and energy, which are among the core symptoms of patients with atypical depression. Thus it can be speculated that noradrenergic antidepressants might be superior to serotonergic antidepressants in reducing symptoms of atypical depression. This is the first study to compare the efficacy of fluoxetine, a selective reuptake inhibitor of serotonin, and reboxetine, a selective reuptake inhibitor of norepinephrine, in the treatment of patients with atypical depression. A total of 43 patients with atypical depression according to DSM-IV were randomly assigned to receive fluoxetine or reboxetine over an 8-wk clinical trial. Patients with a Structured Clinical Interview for DSM-IV diagnosis of personality disorder accounted for 54% of those with atypical depression in this sample. Patients with personality disorders were typically young and were unable to maintain a marriage. Adverse effects such as dry mouth, sweating, headache, and urinary retention were more prominent in the reboxetine group than among those given fluoxetine. Although a greater number of patients treated with reboxetine dropped out of treatment, the pattern of response was very similar for both drugs, and both were effective in reducing symptoms of depression. The presence of a personality disorder in patients with atypical depression did not affect the response to either of the antidepressants. These findings might suggest that drugs with norepinephrine or a 5 hydroxytryptamine mechanism of action might act through a common pathway, resulting in a similar response in terms of core symptoms of depression. If tolerability, efficacy, and cost-effectiveness of antidepressants are considered, the best antidepressant is the one that can be used by the patient, whether or not a personality disorder accompanies atypical depression. PMID- 17276966 TI - The prevalence of insulin resistance in nondiabetic nonobese patients with chronic kidney disease. AB - This study was undertaken to evaluate the prevalence of insulin resistance (IR) and associated factors in nondiabetic, nonobese patients with chronic kidney disease (CKD) who had not yet received dialysis therapy. A group of 89 consecutive patients (42 male, 47 female) who were hospitalized in the Nephrology Clinic at Dicle University, had recently been diagnosed with CKD, and had not yet been treated with dialysis were enrolled in the study, as was a control group of 30 healthy volunteers. Diabetic and obese patients were excluded. IR was determined by the homeostasis model assessment of IR (HOMA-IR) formula. Blood samples were taken after an overnight fasting period to establish serum glucose, insulin, C-peptide, albumin, lipid profile, hematocrit, bicarbonate, and intact parathormone (iPTH) levels. The mean age of patients was 48.7+/-19.7 y (men, 49.5+/-21.5 y; women, 48.1+/-18.0 y); other mean values were as follows: glucose, 98.4+/-20.6 mg/dL; insulin, 16.7+/-16.2 microU/mL; HOMA-IR, 5.46+/-1.14; hemoglobin (Hgb), 8.7+/-1.6 g/dL; calcium-phosphorus product (Ca x P), 52.2+/ 16.2 mg2/dL2; iPTH, 377.7+/-258.1 pg/mL, and bicarbonate (HCO3), 16.6+/-5.3 mEq/L. HOMA-IR was significantly higher in patients with stage 4 CKD than in controls (P<.001); serum levels of urea, creatinine clearance (CrCl), C-reactive protein (CRP), albumin, total cholesterol, high-density lipoprotein cholesterol (HDL-C), Hgb, HCO3, Ca x P, and iPTH were found to be associated with HOMA-IR when a comparison was made with the control group. According to correlation analyses of possible risk factors in patients with IR, positive correlations with age, body mass index, CRP, Ca x P product, and iPTH, and negative correlations with albumin, CrCl, Hgb, and HDL-C were found. A high percentage of IR was found, and this percentage increased as glomerular filtration rate decreased in patients with stage 4 CKD. In addition, a correlation was found between IR and parameters such as age, body mass index, CRP, Ca x P, iPTH, albumin, CrCl, Hgb, and HDL-C. PMID- 17276967 TI - The impact of urinary incontinence on female sexual function. AB - Although urinary incontinence is not a life-threatening disorder, it has been shown to have detrimental effects on quality of life in terms of psychological, social, and sexual problems. In this study, investigators explored the effects of different types of urinary incontinence on female sexual function with a reliable and validated questionnaire, the Female Sexual Function Index (FSFI). One hundred fifty-three women with complaints of incontinence were enrolled in the study. An age-matched group of 89 women who had no incontinence or lower urinary tract disorders were enrolled as a control group; all completed the FSFI. Incontinence was classified as urge, stress, and mixed type. Pelvic organ prolapse (POP), if present, was also recorded. FSFI scores were compared between the incontinent and control groups. A multivariate linear regression analysis model was used to explore the effects of patient characteristics on total FSFI domain score. All domain scores of FSFI except lubrication and pain were statistically significant in the incontinence group (for total domain score, P=.005). For FSFI, in terms of types of incontinence, the difference was significant when the group with mixed urinary incontinence was compared with the control group. In multivariate linear regression analysis, age, presence of POP, and mode of delivery were predictors of female sexual function. Mixed urinary incontinence, when compared with other types, had a significant impact on sexual function. When POP was also present, no negative effects were noted in incontinent women. PMID- 17276968 TI - Incidence of ischemic brain lesions in hyperbaric chamber inside attendants. AB - Concern is growing about the negative long-term effects of hyperbaric exposure on the central nervous system of divers. This study was conducted with magnetic resonance imaging (MRI) to evaluate attendants that work inside hyperbaric chambers (known as inside attendants) for hyperintense brain lesions. Ten inside attendants and 10 healthy nondiving subjects were included in the study. A questionnaire was used to obtain information about subjects' medical history, hyperbaric exposure history, alcohol intake, and smoking habits. T1-weighted, T2 weighted, and fluid-attenuated inversion recovery images were acquired with a 1.5 T MRI device. A lesion was included in the count if it was hyperintense on both T2-weighted and fluid-attenuated inversion recovery images. Although MRI revealed 3 hyperintense brain lesions in 2 of 10 inside attendants and in none of the controls, the differences between groups were not statistically significant (P=.147). The number of brain lesions counted did not correlate with the age of the inside attendants (r=0.007; P=.978), the number of hyperbaric exposures (r= 0.203; P=.574), or the duration of work as an inside attendant (r=0.051; P=.890). Investigators found a correlation, however, between the number of cigarettes smoked in a day and the number of brain lesions identified (r=0.779; P<.01). An increased incidence of hyperintense brain lesions was not observed in inside attendants who had never experienced decompression sickness compared with nondiving controls. Additional multicenter epidemiologic studies are needed if the occupational safety of inside attendants is to be enhanced. PMID- 17276969 TI - Effects of sibutramine on thermogenesis in obese patients assessed via immersion calorimetry. AB - Glucose utilization studies show that sibutramine-induced thermogenesis is mediated via selective sympathetic activation of brown adipose tissue. The goal of the present study was to use a new calorimetry method in which resting metabolic rate is enhanced to evaluate the effects of sibutramine treatment on thermogenesis. Sixty obese women were included in the study. Subjects were divided into 2 equal groups-the placebo and sibutramine treatment groups. The sibutramine group was given sibutramine 10 mg daily for 12 wk. At baseline and at the end of the 12-wk treatment period, thermogenic measurements were taken with the use of water immersion calorimetry. Subjects were examined at weeks 4, 8, and 12 of treatment to identify adverse effects. Body mass index, measured at 31.5+/ 2.05 kg/m2 in the placebo group, decreased to 30.4+/-2.94 kg/m(2) after 12 wk (P=.07). In the sibutramine group, it decreased from 33.5+/-4.1 kg/m(2) to 30.9+/ 4.8 kg/m(2) (P<.05). In the sibutramine group, mean thermogenic response changed from a baseline value of 1.27+/-0.29 kcal/kg/h to 1.44+/-0.13 kcal/kg/h after 12 wk of treatment. In the placebo group, the baseline value was 1.56+/-0.27 kcal/kg/h; it changed to 1.33+/-0.36 kcal/kg/h at the end of 12 wk. The findings of this study suggest that sibutramine treatment promotes thermogenesis, thus facilitating weight loss. Calorimetry enhances resting metabolism through more efficient heat transfer from the body. PMID- 17276970 TI - Pitfalls in radiologic and histopathologic diagnosis of urologic disease--report of 4 cases. AB - Cases are presented to illustrate pitfalls in radiologic and histopathologic diagnosis in urology. In a 73-year-old woman, ultrasound revealed calcification in an irregular mass arising from the left wall of the bladder. Bladder biopsy reported the mass as papillary transitional cell carcinoma. Histologically, the specimen showed marked hyperplasia of the urothelium with formation of Brunn's nests and no evidence of dysplasia or malignancy. A review of medical images showed that the mass was a calcified uterine fibroid. In a 36-year-old man, a calcified opacity in the pelvis was reported as a ureteric calculus, and the patient underwent ureteroscopy. No stone was found. A review of an intravenous urogram showed that the radio-opaque shadow appeared outside the left ureter. A 41-year-old man with tetraplegia developed hydronephrosis as the result of a calculus in the renal pelvis. Ureteric stenting was performed, followed by shock wave lithotripsy. A follow-up x-ray of the abdomen showed a small radioopacity that projected over the line of the left ureter at the L-3 level-probably a ureteric calculus. A review of a computed tomography scan revealed that the calculus, noted on plain film at the level of L-3, had become extruded and was lying posterior to the ureter. A 59-year-old man underwent nephrectomy for a 5-cm solid lesion in the mid pole of the left kidney. Histology showed multiple synchronous renal cell carcinomas and angiomyolipomas. The patient underwent further investigation for von Hippel-Lindau disease and tuberous sclerosis. A review of tissue blocks from the nephrectomy specimen, however, showed no evidence of angiomyolipoma. What was interpreted as renal angiomyolipoma was actually simple distorted blood vessels in areas of renal scarring. To prevent mistakes in diagnosis and to detect medical errors without delay, the authors recommend that physicians set aside time to reflect upon their clinical practice, regularly participate in honest and informal case discussions, and seek a second opinion when in doubt. PMID- 17276971 TI - Reward deficiency syndrome in obesity: a preliminary cross-sectional trial with a Genotrim variant. AB - Obesity is the second largest preventable cause of death in the United States. Even though it was classified as a disease in 1985, traditionally, obesity has been treated primarily as a behavioral problem that requires only modifications in diet and exercise. Similar to research on obesity, clinical studies have elucidated the role of biologic and genetic factors in alcoholism and other conditions previously classified as behavioral. These studies showed that behavioral adjustments alone may not address underlying genetic causes. We hypothesize that biologic and genetic factors must be addressed synergistically while behavioral modifications are implemented to adequately treat obese patients. We hypothesize that a predisposition to glucose craving and obesity is due to inadequate dopaminergic activity in the reward center of the brain. This defect drives individuals to engage in activities of behavioral excess, which, in turn, enhance brain dopamine function. Consumption of large quantities of alcohol or carbohydrates (carbohydrate bingeing) stimulates production and usage of dopamine within the brain; the term reward deficiency syndrome (RDS) may be used to categorize such biologic influences on behavior. We propose that a novel approach to nutritional supplementation may be required to target the role of RDS in obesity. In this regard, GenoTrim, a DNA-customized nutritional solution, has been developed and is currently under investigation in several clinical studies. Through its mechanism of action, GenoTrim addresses the genetic influence of RDS on obesity. In this cross-sectional study, 24 subjects were studied after they had completed a case report format questionnaire. For this assessment, we used a novel assessment tool-a path analysis. This statistical regression model is used to (1) examine the effectual relationships between various systems within a multisystem matrix, and (2) measure the contributory roles of those relationships in obesity, enabling the development of targeted and effective therapeutic interventions. PMID- 17276972 TI - Evaluation of tumor markers CA-125 and CEA in acute myocardial infarction. AB - Serum carbohydrate antigen (CA-125) and carcinoembryonic antigen (CEA) have always been of clinical importance in the diagnosis and follow-up of various tumors. This study was devised to investigate the relationship between these tumor markers and acute myocardial infarction (MI). Seventy consecutive cases (59 male patients with a diagnosis of acute ST segment elevation MI and 11 male patients with a diagnosis of non-ST segment elevation MI; mean age, 57+/-8.2 y) were admitted to the University Medical Center and were included in this study as "the patient group." All patients in the patient group underwent transthoracic echocardiographic examination on the third day of hospitalization. On the basis of echocardiographic findings, these 70 patients were grouped according to left ventricular ejection fraction (EF) values; EF <55% (group 1) (n=40) and EF >or=55% (group 2) (n=30). Other parameters, including systolic pulmonary artery pressure (sPAP) and mean pulmonary artery pressure (mPAP), were also measured on transthoracic echocardiography. Serial blood samples (for follow-up of myocardial enzymes (eg, creatine kinase MB [CKMB], troponin I [TnI], troponin T, and other routine parameters) were drawn from each patient. Serum concentrations of CEA and CA-125 measured at the 72nd hour of hospitalization and peak serum concentrations of CKMB and TnI in the patient group were collected for comparison between subgroups (groups 1 and 2) and with "the control group," which included 30 subjects (mean age, 54+/-7.6 y) with no history or evidence of overt cardiac disease and with normal echocardiographic findings. The presence of any condition characterized by potential elevations in CA-125, CEA, and myocardial enzymes (CKMB, TnI) was considered an exclusion criterion. Patients included in patient groups 1 and 2 differed significantly in terms of mean EF, mean sPAP, mean mPAP, and mean CA-125 values (P<.001 for CA-125; P<.05 for the other values). EF was found to be negatively correlated with sPAP (r=-0.692, P=.000) and mPAP (r= 0.393, P=.001). EF was also negatively correlated with CA-125 (r=-0.557, P=.000). A positive correlation was noted between CA-125 and sPAP (r=0.396, P=.001) and between CA-125 and mPAP (r=0.754, P=.000). A statistically significant difference was identified between the patient and control groups with regard to values for EF, PAP, CA-125, and myocardial enzymes (CKMB and TnI) (P<.05 for mPAP; P<.001 for the other values). The serum concentration of CA-125, but not of CEA, may be elevated in those with acute MI compared with normal subjects. Regardless of the presence of pulmonary hypertension, elevations in CA-125 during myocardial infarction were significantly correlated with the severity of left ventricular systolic dysfunction on transthoracic echocardiography. PMID- 17276973 TI - Clinical importance of elevated CK-MB and troponin I levels in congestive heart failure. AB - Myocyte necrosis has been considered to play a fundamental role in the pathophysiology of congestive heart failure (CHF), which has usually evolved as a consequence of depletion of compensatory mechanisms and contractile reserve of myocardium. Elevated levels of creatine kinase MB (CK-MB) and troponin I (Tn-I) have been regarded as biochemical markers of myocyte necrosis. This study was planned to investigate the specificity and sensitivity of Tn-I and CK-MB in CHF and to examine the correlation of these markers with disease severity. A total of 104 patients (38 female, 66 male; mean age, 66 y [range, 36-89]) with symptoms and signs of heart failure on admission and with a reduced left ventricular ejection fraction (EF; by transthoracic echocardiography) were labeled "the patient group," and 58 patients (40 female,18 male; mean age, 61 y [range, 34 77]) with no signs or symptoms of CHF and with a normal EF detected by transthoracic echocardiography were included in the study as "the control group." Left ventricular EFs, end-diastolic diameters, and end-systolic diameters of patients in both groups were measured. Blood samples were drawn from all patients in both groups on admission, so that levels of CK-MB and Tn-I could be measured. All patients in both groups also underwent coronary angiography. Conditions leading to elevation of CK-MB or Tn-I were considered exclusion criteria. The 2 groups failed to show any significant differences in terms of mean age and the presence of coronary artery disease, hypertension, or diabetes mellitus (P>.05). Mean EF in the patient group was lower than that in the control group (P<.05). Mean CK-MB and Tn-I in the patient group were significantly higher than in the control group (P<.05). In the patient group, hypertensive patients were found to have significantly higher mean values of CK-MB than were seen in normotensive patients in the same group (P<.05). In the patient group, 52 cases were considered to be class I-II (New York Heart Association [NYHA]) (group 1), and 52 were considered to be class III-IV (group 2). Group 1, group 2, and the control group did not differ significantly from one another with regard to the presence of coronary artery disease, hypertension, and diabetes mellitus (P>.05). The mean EF in group 2 was significantly lower than that in group 1 and in the control group (P<.05); the mean EF in group 1 was significantly lower than that in the control group (P<.05). Group 1 values did not differ significantly from those of group 2 or the control group in terms of enzymatic markers (P>.05), but group 2 had significantly higher mean values of CK-MB and Tn-I than were noted in the control group (P<.05). The uphill course of CK-MB and Tn-I values from the control group to group 2 (NYHA class III-IV) was statistically significant (P<.05). Serum concentrations of CK-MB and Tn-I may become elevated in severely symptomatic patients with CHF (particularly NYHA class III-IV), demonstrating a relationship between clinical severity of the disease and elevation of myocardial enzymes (CK-MB and Tn-I). PMID- 17276974 TI - Binasal cannula versus face mask for oxygen therapy in patients with chronic pulmonary disease. AB - Oxygen therapy, which is ordered frequently for patients with chronic pulmonary disease, remains a cornerstone of modern medical practice. This study was conducted to compare the efficiency and comfort of a binasal cannula versus a face mask during oxygen therapy. Sixty hypoxemic patients participated in this randomized controlled study. While each patient was hypoxemic, arterial blood gas analysis was performed before oxygen supplementation was begun. Arterial oxygen saturation was continuously monitored during oxygen therapy with a face mask or a binasal cannula. Subjects were allowed to return to their oxygen saturation level in room air before the device for oxygen treatment was changed. The same procedure was then repeated with the other device. Patient comfort was evaluated through the use of a questionnaire that was completed after each treatment period. The mean age+/-standard deviation was 62+/-13 y. No statistically significant difference was noted in oxygen saturation levels achieved with the 2 devices. The binasal cannula reached target oxygen levels (P=.007) more quickly than the face mask. The binasal cannula was reported to be significantly more comfortable (P=.0001), and had significantly fewer reports of dyspnea and restlessness, and was less of a nuisance (P=.019, P=.0001, and P=.0001, respectively). The binasal cannula was preferred for oxygen therapy by 71% of study patients. Although the efficiency of the 2 devices did not differ remarkably, the binasal cannula was regarded as a more comfortable and time saving device for delivery of oxygen therapy to hypoxic patients. PMID- 17276975 TI - The scolicidal effects of honey. AB - Echinococcosis is a zoonosis that is caused by adult or larval tapeworms belonging to the genus Echinococcus. Until now, no studies have sought to determine the scolicidal effects of honey. Therefore, the present study was undertaken to explore the scolicidal effects of honey in different concentrations for various exposure times. Tubes that contained at least 500 protoscolices were supplemented with 1%, 5%, 10%, 25%, and 50% concentrations of honey. Tubes were maintained at room temperature for 0.5, 1, 2, 3, 4, 5, and 10 min. At the end of the incubation times, the viability of protoscolices was assessed through a trypan blue exclusion test. The effective dose of honey was applied intraperitoneally to determine whether it caused an anaphylactic reaction or hyperglycemia. Honey concentrations of 10% or greater killed all protoscolices. The scolicidal effects of honey began at the end of the third minute. Honey did not cause adverse effects when applied intraperitoneally. In this study, an investigation of the scolicidal effects of honey showed that it is highly effective at a 10% concentration. On the basis of in vivo study results, the investigators concluded that honey is a potent scolicidal agent. PMID- 17276976 TI - Modeling human papillomavirus vaccine effectiveness: quantifying the impact of parameter uncertainty. AB - The development of models is based on assumptions, which inevitably embed a level of uncertainty. Quantifying such uncertainty is particularly important when modeling human papillomavirus (HPV) vaccine effectiveness; the natural history of infection and disease is complex, and age- and type-specific data remain scarce and incomplete. The aim of this study was to predict the impact of HPV-6/11/16/18 vaccination, using a cohort model and measuring parameter uncertainty. An extensive fitting procedure was conducted, which identified 164 posterior parameter combinations (out of 200,000 prior parameter sets) that fit simultaneously HPV type-specific incidence and prevalence data for infection, cervical intraepithelial neoplasia (CIN), and squamous cell carcinoma (SCC). Results based on these posterior parameter sets suggest that vaccinating girls aged 12 years (vaccine efficacy = 95%, no waning) would reduce their lifetime risk of HPV infection, CIN1, CIN2/3, and SCC by 21% (80% credibility interval: 17, 29), 24% (80% credibility interval: 17, 31), 49% (80% credibility interval: 36, 60), and 61% (80% credibility interval: 47, 73), respectively. If vaccine efficacy is reduced or vaccine protection is assumed to wane, uncertainty surrounding predictions widens considerably. Important priorities for future research are to understand the role of natural immunity and to measure the duration of vaccine protection because results were most sensitive to these parameters. PMID- 17276977 TI - GH3-mediated auxin homeostasis links growth regulation with stress adaptation response in Arabidopsis. AB - Plants constantly monitor environmental fluctuations to optimize their growth and metabolism. One example is adaptive growth occurring in response to biotic and abiotic stresses. Here, we demonstrate that GH3-mediated auxin homeostasis is an essential constituent of the complex network of auxin actions that regulates stress adaptation responses in Arabidopsis. Endogenous auxin pool is regulated, at least in part, through negative feedback by a group of auxin-inducible GH3 genes encoding auxin-conjugating enzymes. An Arabidopsis mutant, wes1-D, in which a GH3 gene WES1 is activated by nearby insertion of the (35)S enhancer, exhibited auxin-deficient traits, including reduced growth and altered leaf shape. Interestingly, WES1 is also induced by various stress conditions as well as by salicylic acid and abscisic acid. Accordingly, wes1-D was resistant to both biotic and abiotic stresses, and stress-responsive genes, such as pathogenesis related genes and CBF genes, were upregulated in this mutant. In contrast, a T DNA insertional mutant showed reduced stress resistance. We therefore propose that GH3-mediated growth suppression directs reallocation of metabolic resources to resistance establishment and represents the fitness costs of induced resistance. PMID- 17276978 TI - TAK1 MAPK kinase kinase mediates transforming growth factor-beta signaling by targeting SnoN oncoprotein for degradation. AB - Transforming growth factor-beta (TGF-beta) regulates a variety of physiologic processes through essential intracellular mediators Smads. The SnoN oncoprotein is an inhibitor of TGF-beta signaling. SnoN recruits transcriptional repressor complex to block Smad-dependent transcriptional activation of TGF-beta-responsive genes. Following TGF-beta stimulation, SnoN is rapidly degraded, thereby allowing the activation of TGF-beta target genes. Here, we report the role of TAK1 as a SnoN protein kinase. TAK1 interacted with and phosphorylated SnoN, and this phosphorylation regulated the stability of SnoN. Inactivation of TAK1 prevented TGF-beta-induced SnoN degradation and impaired induction of the TGF-beta responsive genes. These data suggest that TAK1 modulates TGF-beta-dependent cellular responses by targeting SnoN for degradation. PMID- 17276979 TI - Golgi GDP-fucose transporter-deficient mice mimic congenital disorder of glycosylation IIc/leukocyte adhesion deficiency II. AB - Modification of glycoproteins by the attachment of fucose residues is widely distributed in nature. The importance of fucosylation has recently been underlined by identification of the monogenetic inherited human disease "congenital disorder of glycosylation IIc," also termed "leukocyte adhesion deficiency II." Due to defective Golgi GDP-fucose transporter (SLC35C1) activity, patients show a hypofucosylation of glycoproteins and present clinically with mental and growth retardation, persistent leukocytosis, and severe infections. To investigate effects induced by the loss of fucosylated structures in different organs, we generated a mouse model for the disease by inactivating the Golgi GDP transporter gene (Slc35c1). Lectin binding studies revealed a tremendous reduction of fucosylated glycoconjugates in tissues and isolated cells from Slc35c1(-/-) mice. Fucose treatment of cells from different organs led to partial normalization of the fucosylation state of glycoproteins, thereby indicating an alternative GDP-fucose transport mechanism. Slc35c1-deficient mice presented with severe growth retardation, elevated postnatal mortality rate, dilatation of lung alveoles, and hypocellular lymph nodes. In vitro and in vivo leukocyte adhesion and rolling assays revealed a severe impairment of P-, E-, and L-selectin ligand function. The diversity of these phenotypic aspects demonstrates the broad general impact of fucosylation in the mammalian organism. PMID- 17276980 TI - Mechanism of inactivation of plasminogen activator inhibitor-1 by a small molecule inhibitor. AB - The inactivation of plasminogen activator inhibitor-1 (PAI-1) by the small molecule PAI-1 inhibitor PAI-039 (tiplaxtinin) has been investigated using enzymatic analysis, direct binding studies, site-directed mutagenesis, and molecular modeling studies. Previously PAI-039 has been shown to exhibit in vivo activity in various animal models, but the mechanism of inhibition is unknown. PAI-039 bound specifically to the active conformation of PAI-1 and exhibited reversible inactivation of PAI-1 in vitro. SDS-PAGE indicated that PAI-039 inactivated PAI-1 predominantly through induction of PAI-1 substrate behavior. Preincubation of PAI-1 with vitronectin, but not bovine serum albumin, blocked PAI-039 activity while analysis of the reciprocal experiment demonstrated that preincubation of PAI-1 with PAI-039 blocked the binding of PAI-1 to vitronectin. Together, these data suggest that the site of interaction of the drug on PAI-1 is inaccessible when PAI-1 is bound to vitronectin and may overlap with the PAI-1 vitronectin binding domain. This was confirmed by site-directed mutagenesis and molecular modeling studies, which suggest that the binding epitope for PAI-039 is localized adjacent to the previously identified interaction site for vitronectin. Thus, these studies provide a detailed characterization of the mechanism of inhibition of PAI-1 by PAI-039 against free, but not vitronectin-bound PAI-1, suggesting for the first time a novel pool of PAI-1 exists that is vulnerable to inhibition by inactivators that bind at the vitronectin binding site. PMID- 17276982 TI - Actions of aprataxin in multiple DNA repair pathways. AB - Mutations in the Aptx gene lead to a neurological disorder known as ataxia oculomotor apraxia-1. The product of Aptx is Aprataxin (Aptx), a DNA-binding protein that resolves abortive DNA ligation intermediates. Aprataxin catalyzes the nucleophilic release of adenylate groups covalently linked to 5' phosphate termini, resulting in termini that can again serve as substrates for DNA ligases. Here we show that Aprataxin acts preferentially on adenylated nicks and double strand breaks rather than on single-stranded DNA. Moreover, we show that whereas the catalytic activity of Aptx resides within the HIT domain, the C-terminal zinc finger domain provides stabilizing contacts that lock the enzyme onto its high affinity AMP-DNA target site. Both domains are therefore required for efficient AMP-DNA hydrolase activity. Additionally, we find a role for Aprataxin in base excision repair, specifically in the removal of adenylates that arise from abortive ligation reactions that take place at incised abasic sites in DNA. We suggest that Aprataxin may have a general proofreading function in DNA repair, removing DNA adenylates as they arise during single-strand break repair, double strand break repair, and in base excision repair. PMID- 17276981 TI - p53-Dependent Aph-1 and Pen-2 anti-apoptotic phenotype requires the integrity of the gamma-secretase complex but is independent of its activity. AB - The presenilin-dependent gamma-secretase activity, which is responsible for the generation of amyloid beta-peptide, is a high molecular weight complex composed of at least four components, namely, presenilin-1 (or presenilin-2), nicastrin, Aph-1, and Pen-2. Previous data indicated that presenilins, which are thought to harbor the catalytic core of the complex, also control p53-dependent cell death. Whether the other components of the gamma-secretase complex could also modulate the cell death process in mammalian neurons remained to be established. Here, we examined the putative contribution of Aph-1 and Pen-2 in the control of apoptosis in TSM1 cells from a neuronal origin. We show by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and DNA fragmentation analyses that the overexpression of Aph-1a, Aph-1b, or Pen-2 drastically lowered staurosporine induced cellular toxicity. In support of an apoptosis rather than necrosis process, Aph-1 and Pen-2 also lower staurosporine- and etoposide-induced caspase 3 expression and diminished caspase-3 activity and poly(ADP-ribose) polymerase inactivation. The Aph-1 and Pen-2 anti-apoptotic phenotype was associated with a drastic reduction of p53 expression and activity and lowered p53 mRNA transcription. Furthermore, the Aph-1- and Pen-2-associated reduction of staurosporine-induced caspase-3 activation was fully abolished by p53 deficiency. Conversely, Aph-1a, Aph-1b, and Pen-2 gene inactivation increases both caspase-3 activity and p53 mRNA levels. Finally, we show that Aph-1 and Pen-2 did not trigger an anti-apoptotic response in cells devoid of presenilins or nicastrin, whereas the protective response was still observed in fibroblasts devoid of beta amyloid precursor protein and amyloid precursor protein like-protein 2. Furthermore, Aph-1- and Pen-2-associated protection against staurosporine-induced caspase-3 activation was not affected by the gamma-secretase inhibitors N-[N-(3,5 difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester and difluoromethylketone. Altogether, our study indicates that Aph-1 and Pen-2 trigger an anti-apoptotic response by lowering p53-dependent control of caspase 3. Our work also demonstrates that this phenotype is strictly dependent on the molecular integrity of the gamma-secretase complex but remains independent of the gamma-secretase catalytic activity. PMID- 17276983 TI - Molecular and functional analyses of a novel class I secretory nuclease from the human pathogen, Leishmania donovani. AB - The primitive protozoan pathogen of humans, Leishmania donovani, resides and multiplies in highly restricted micro-environments within their hosts (i.e. as promastigotes in the gut lumen of their sandfly vectors and as amastigotes in the phagolysosomal compartments of infected mammalian macrophages). Like other trypanosomatid parasites, they are purine auxotrophs (i.e. lack the ability to synthesize purines de novo) and therefore are totally dependent upon salvaging these essential nutrients from their hosts. In that context, in this study we identified a unique 35-kDa, dithiothreitol-sensitive nuclease and showed that it was constitutively released/secreted by both promastigote and amastigote developmental forms of this parasite. By using several different molecular approaches, we identified and characterized the structure of LdNuc(s), a gene that encodes this new 35-kDa class I nuclease family member in these organisms. Homologous episomal expression of an epitope-tagged LdNuc(s) chimeric construct was used in conjunction with an anti-LdNuc(s) peptide antibody to delineate the functional and biochemical properties of this unique 35-kDa parasite released/secreted enzyme. Results of coupled immunoprecipitation-enzyme activity analyses demonstrated that this "secretory" enzyme could hydrolyze a variety of synthetic polynucleotides as well as several natural nucleic acid substrates, including RNA and single- and double-stranded DNA. Based on these cumulative observations, we hypothesize that within the micro-environments of its host, this leishmanial "secretory" nuclease could function at a distance away from the parasite to harness (i.e. hydrolyze/access) host-derived nucleic acids to satisfy the essential purine requirements of these organisms. Thus, this enzyme might play an important role(s) in facilitating the survival, growth, and development of this important human pathogen. PMID- 17276984 TI - The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. AB - Dengue virus (DV) is a positive sense RNA virus replicating in the cytoplasm in membranous compartments that are induced by viral infection. The non-structural protein (NS) 4A is one of the least characterized DV proteins. It is highly hydrophobic with its C-terminal region (designated 2K fragment) serving as a signal sequence for the translocation of the adjacent NS4B into the endoplasmic reticulum (ER) lumen. In this report, we demonstrate that NS4A associates with membranes via 4 internal hydrophobic regions, which are all able to mediate membrane targeting of a cytosolic reporter protein. We also developed a model for the membrane topology of NS4A in which the N-terminal third of NS4A localizes to the cytoplasm, while the remaining part contains three transmembrane segments, with the C-terminal end localized in the ER lumen. Subcellular localization experiments in DV-infected cells revealed that NS4A resides primarily in ER derived cytoplasmic dot-like structures that also contain dsRNA and other DV proteins, suggesting that NS4A is a component of the membrane-bound viral replication complex (RC). Interestingly, the individual expression of DV NS4A lacking the 2K fragment resulted in the induction of cytoplasmic membrane alterations resembling virus-induced structures, whereas expression of full length NS4A does not induce comparable membrane alterations. Thus, proteolytic removal of the 2K peptide appears to be important for induction of membrane alterations that may harbor the viral RC. These results shed new light on the role of NS4A in the DV replication cycle and provide a model of how this protein induces membrane rearrangements and how this property may be regulated. PMID- 17276985 TI - Alterations in linker flexibility suppress DNA topoisomerase I mutant-induced cell lethality. AB - Eukaryotic DNA topoisomerase I (Top1p) catalyzes changes in DNA topology via the formation of a covalent enzyme-DNA intermediate, which is reversibly stabilized by the anticancer agent camptothecin (CPT). Crystallographic studies of the 70 kDa C terminus of human Top1p bound to duplex DNA describe a monomeric protein clamp circumscribing the DNA helix. The structures, which lack the N-terminal domain, comprise the conserved clamp, an extended linker domain, and the conserved C-terminal active site Tyr domain. CPT bound to the covalent Top1p-DNA complex limits linker flexibility, allowing structural determination of this domain. We previously reported that mutation of Ala(653) to Pro in the linker increases the rate of enzyme-catalyzed DNA religation, thereby rendering Top1A653Pp resistant to CPT (Fiorani, P., Bruselles, A., Falconi, M., Chillemi, G., Desideri, A., and Benedetti P. (2003) J. Biol. Chem. 278, 43268-43275). Molecular dynamics studies suggested mutation-induced increases in linker flexibility alter Top1p catalyzed DNA religation. To address the functional consequences of linker flexibility on enzyme catalysis and drug sensitivity, we investigated the interactions of the A653P linker mutation with a self-poisoning T718A mutation within the active site of Top1p. The A653P mutation suppressed the lethal phenotype of Top1T718Ap in yeast, yet did not restore enzyme sensitivity to CPT. However, the specific activity of the double mutant was decreased in vivo and in vitro, consistent with a decrease in DNA binding. These findings support a model where changes in the flexibility or orientation of the linker alter the geometry of the active site and thereby the kinetics of DNA cleavage/religation catalyzed by Top1p. PMID- 17276986 TI - Specific features of the prion protein transmembrane domain regulate nascent chain orientation. AB - The sequence of a transmembrane (TM) domain and the adjacent regions are important for recognition, orientation, and integration at the translocon during membrane protein biosynthesis. However, the sequences of individual TM domains vary considerably. Although some general effects of electrostatic and hydrophobic interactions have been observed, it is still not clear what features of diverse sequences influence TM domain orientation. Here we utilized the ability of the prion protein (PrP) to be synthesized in multiple topological forms to assay the effects of substitutions and mutations on TM domain orientation. Several of the TM domains we tested appear to contain no inherent information regulating orientation. In contrast, we found that the middle region of the PrP TM domain significantly reduces the ability of the chain to invert its orientation in the translocon. We also observed that the C-terminal region of the PrP TM domain influences orientation, and we characterized the orientation differences between two forms of a physiologically relevant polymorphism in this region. Specifically, we found that the identity of a single amino acid, that at position 129, can significantly alter PrP TM domain orientation. Because position 129 is the location of the disease-associated Met/Val polymorphism, we discuss both how this small change may affect TMD orientation and the larger biological implications of these results. PMID- 17276987 TI - The brefeldin A-inhibited guanine nucleotide-exchange protein, BIG2, regulates the constitutive release of TNFR1 exosome-like vesicles. AB - The type I, 55-kDa tumor necrosis factor receptor (TNFR1) is released from cells to the extracellular space where it can bind and modulate TNF bioactivity. Extracellular TNFR1 release occurs by two distinct pathways: the inducible proteolytic cleavage of TNFR1 ectodomains and the constitutive release of full length TNFR1 in exosome-like vesicles. Regulation of both TNFR1 release pathways appears to involve the trafficking of cytoplasmic TNFR1 vesicles. Vesicular trafficking is controlled by ADP-ribosylation factors (ARFs), which are active in the GTP-bound state and inactive when bound to GDP. ARF activation is enhanced by guanine nucleotide-exchange factors that catalyze replacement of GDP by GTP. We investigated whether the brefeldin A (BFA)-inhibited guanine nucleotide-exchange proteins, BIG1 and/or BIG2, are required for TNFR1 release from human umbilical vein endothelial cells. Effects of specific RNA interference (RNAi) showed that BIG2, but not BIG1, regulated the release of TNFR1 exosome-like vesicles, whereas neither BIG2 nor BIG1 was required for the IL-1beta-induced proteolytic cleavage of TNFR1 ectodomains. BIG2 co-localized with TNFR1 in diffusely distributed cytoplasmic vesicles, and the association between BIG2 and TNFR1 was disrupted by BFA. Consistent with the preferential activation of class I ARFs by BIG2, ARF1 and ARF3 participated in the extracellular release of TNFR1 exosome-like vesicles in a nonredundant and additive fashion. We conclude that the association between BIG2 and TNFR1 selectively regulates the extracellular release of TNFR1 exosome like vesicles from human vascular endothelial cells via an ARF1- and ARF3 dependent mechanism. PMID- 17276988 TI - Cell confluence-induced activation of signal transducer and activator of transcription-3 (Stat3) triggers epithelial dome formation via augmentation of sodium hydrogen exchanger-3 (NHE3) expression. AB - Cell confluence induces the activation of signal transducer and activator of transcription-3 (Stat3) in various cancer and epithelial cells, yet the biological implications and the associated regulatory mechanisms remain unclear. Because confluent polarized epithelia demonstrate dome formation and sodium influx that mimic the onset of differentiation, we sought to elucidate the role of Stat3 in association with the regulation of selective epithelial transporters in this biological phenomenon. This study established the correlation between Stat3 activation and cell confluence-induced dome formation in Madin-Darby canine kidney cells (MDCK) by following Stat3 activation events in dome-forming cells. Epifluorescent and confocal microscopy provided evidence showing specific localization of phosphorylated Stat3 Tyr(705) in the nuclei of dome-forming cells at initial stages. The relationship was further elucidated by the establishment of tetracycline-inducible expression of constitutive Stat3 mutant (Stat3-C) in MDCK cells or expression of dominant negative Stat3 (Stat3-D) stable cell lines (MDCK and NMuMG). Dome formation was promoted by the expression of Stat3-C but inhibited by Stat3-D. Two trans-epithelial transporters, NHE3 and ENaC alpha subunit, were found to be increased during cell confluence. Interestingly, NHE3 expression could be specifically up-regulated by Stat3-C but inhibited by Stat3-D through promoter regulation, whereas NHE1 and ENaC alpha-subunit were not affected by Stat3 expression. Application of NHE3 shRNA, NHE3 inhibitors (EIPA and S3226) suppressed confluence-induced dome formation in MDCK or NMuMG cells. These results demonstrate a cell confluence-induced Stat3 signaling pathway in epithelial cells in triggering dome formation through NHE3 augmentation. PMID- 17276989 TI - A novel role for the glucocorticoid receptor in the regulation of monocyte chemoattractant protein-1 mRNA stability. AB - Monocyte chemoattractant protein-1 (MCP-1) plays an important role in attracting monocytes to sites of inflammation and is the dominant mediator of macrophage accumulation in atherosclerotic plaques. We have previously shown that glucocorticoids inhibit the secretion of MCP-1 in arterial smooth muscle cells (SMC) by markedly decreasing MCP-1 mRNA stability. We now report that the destabilization of MCP-1 mRNA is mediated by the glucocorticoid receptor (GR). The GR antagonist, RU486, blocked the effect of the glucocorticoid dexamethasone (Dex) on MCP-1 mRNA stability in SMC culture. Using a previously reported in vitro mRNA gel shift and stability assay, antibodies to the GR blocked the ability of cytoplasmic extracts from Dex-treated SMC to decay MCP-1 mRNA. Recombinant human GR (rhGR) bound in a concentration-dependent manner to in vitro transcribed MCP-1 mRNA, whereas other members of the steroid hormone receptor family did not. Binding of GR to MCP-1 mRNA was specific as it was not found to bind other mRNAs. Immunoprecipitation of GR in extracts from Dex-treated SMC followed by real-time reverse transcription-PCR demonstrated that endogenous GR was bound specifically to MCP-1 mRNA. The addition of exogenous rhGR blocked the ability of extracts from Dex-treated SMC to degrade MCP-1 mRNA, suggesting that exogenous rhGR can compete with an endogenous GR-containing degradative complex. These data suggest a novel role for the GR in binding to and facilitating mRNA degradation. These results provide novel insights into GR function and may provide a new approach to attenuate the inflammatory response mediated by MCP-1. PMID- 17276991 TI - Ubiquitin-interacting motifs inhibit aggregation of polyQ-expanded huntingtin. AB - Expansion of polyglutamine (polyQ) tracts within proteins underlies a number of neurodegenerative diseases, such as Huntington disease, Kennedy disease, and spinocerebellar ataxias. The resulting mutant proteins are unstable, forming insoluble aggregates that are associated with components of the ubiquitin system, including ubiquitin, ubiquitin-like proteins, and proteins that bind to ubiquitin. Given the presence of these ubiquitin-binding proteins in the insoluble aggregates, we examined whether heterologous expression of short motifs that bind ubiquitin, termed ubiquitin-interacting motifs (UIMs), altered the aggregation of polyQ-expanded huntingtin (Htt), the protein product of the Huntington disease gene. We found that a subset of UIMs associated with mutant Htt. The ability to interact with ubiquitin was necessary, but not sufficient, for interaction with mutant Htt. Furthermore, we found that expression of single, isolated UIMs inhibited aggregation of mutant Htt. These data suggest that isolated UIMs might serve as potential inhibitors of polyQ-aggregation in vivo. PMID- 17276990 TI - Cdc7-Dbf4 and the human S checkpoint response to UVC. AB - The S checkpoint response to ultraviolet radiation (UVC) that inhibits replicon initiation is dependent on the ATR and Chk1 kinases. Downstream effectors of this response, however, are not well characterized. Data reported here eliminated Cdc25A degradation and inhibition of Cdk2-cyclin E as intrinsic components of the UVC-induced pathway of inhibition of replicon initiation in human cells. A sublethal dose of UVC (1 J/m(2)), which selectively inhibits replicon initiation by 50%, failed to reduce the amount of Cdc25A protein or decrease Cdk2-cyclin E kinase activity. Cdc25A degradation was observed after irradiation with cytotoxic fluences of UVC, suggesting that severe inhibition of DNA chain elongation and activation of the replication checkpoint might be responsible for the UVC-induced degradation of Cdc25A. Another proposed effector of the S checkpoint is the Cdc7 Dbf4 complex. Dbf4 interacted weakly with Chk1 in vivo but was recognized as a substrate for Chk1-dependent phosphorylation in vitro. FLAG-Dbf4 formed complexes with endogenous Cdc7, and this interaction was stable in UVC-irradiated HeLa cells. Overexpression of FLAG- or Myc-tagged Dbf4 abrogated the S checkpoint response to UVC but not ionizing radiation. These findings implicate a Dbf4 dependent kinase as a possible target of the ATR- and Chk1-dependent S checkpoint response to UVC. PMID- 17276992 TI - A network-based analysis of polyanion-binding proteins utilizing human protein arrays. AB - The existence of interactions between many cellular proteins and various polyanionic surfaces within a cell is now well established. The functional role of such interactions, however, remains to be clearly defined. The existence of protein arrays, with a large selection of different kinds of proteins, provides a way to better address a number of aspects of this question. We have therefore investigated the interaction between five cellular polyanions (actin, tubulin, heparin, heparan sulfate, and DNA) and approximately 5,000 human proteins using protein microarrays in an attempt to better understand the functional nature of such interaction(s). We demonstrate that a large number of polyanion-binding proteins exist that contain multiple positively charged regions, are often disordered, are involved in phosphorylation processes, and appear to play a role in protein-protein interaction networks. Considering the crowded nature of cellular interiors, we propose that polyanion-binding proteins interact with a wide variety of polyanionic surfaces in cells in a functionally significant manner. PMID- 17276993 TI - HIV gp41 C-terminal heptad repeat contains multifunctional domains. Relation to mechanisms of action of anti-HIV peptides. AB - T20 (Fuzeon), a novel anti-human immunodeficiency virus (HIV) drug, is a peptide derived from HIV-1 gp41 C-terminal heptad repeat (CHR). Its mechanism of action has not yet been defined. We applied Pepscan strategy to determine the relationship between functional domains and mechanisms of action of five 36-mer overlapping peptides with a shift of five amino acids (aa): CHR-1 (aa 623-658), C36 (aa 628-663), CHR-3 (aa 633-668), T20 (aa 638-673), and CHR-5 (aa 643-678). C36 is a peptide with addition of two aa to the N terminus of C34. Peptides CHR-1 and C36 contain N-terminal heptad repeat (NHR)- and pocket-binding domains. They inhibited HIV-1 fusion by interacting with gp41 NHR, forming stable six-helix bundles and blocking gp41 core formation. Peptide T20 containing partial NHR- and lipid-binding domains, but lacking pocket-binding domain, blocked viral fusion by binding its N- and C-terminal sequences with gp41 NHR and cell membrane, respectively. Peptide CHR-3, which is located in the middle between C36 and T20, overlaps >86% of the sequences of these two peptides, and lacks pocket- and lipid binding domains, exhibited marginal anti-HIV-1 activity. These results suggest that T20 and C36 contain different functional domains, through which they inhibit HIV-1 entry with distinct mechanisms of action. The multiple functional domains in gp41 CHR and their binding partners may serve as targets for rational design of new anti-HIV-1 drugs and vaccines. PMID- 17276995 TI - Prognostic value of the New York Heart Association classification in end-stage renal disease. AB - BACKGROUND: The New York Heart Association (NYHA) classification is a strong predictor of mortality and an established instrument for risk stratification in patients with heart disease but data on the validity of this classification in end-stage renal disease (ESRD) are sparse. METHODS: In this study, we tested the predictive value of the NYHA in patients with ESRD and compared it with that of two established indexes of disease severity, i.e. the Khan index and the renal disease severity score (RDSS). The study cohort was composed of 1322 incident patients in a dialysis registry (772 male and 550 female, age 61+/-16 years). RESULTS: During the follow-up period (41+/-27 months) 551 patients died. A multivariate COX model including the NYHA classification explained 39% of the variation in mortality, a figure almost identical to that of a model based on the RDSS (37%) and superior (P<0.001) to that provided by the Khan index-based model (32%). The area under the receiver operating characteristic curve of NYHA classification, as related to all-cause mortality, was 0.74 (95% CI: 0.71-0.77, P<0.001). Again, RDSS had a predictive value for mortality (0.74, 95% CI: 0.72 0.77) identical to that of NYHA and higher than that of the Khan index (0.70, 95% CI: 0.67-0.72). CONCLUSION: The NYHA is a powerful predictor of mortality in ESRD and provides prognostic information equal or superior to that given by other established indexes of disease severity. Given the pervasive nature of cardiovascular disease in ESRD, this classification may be recommended for risk stratification in this population. PMID- 17276996 TI - Radiation protection and international intrigue. PMID- 17276994 TI - Hepatitis B vaccine and risk of relapse after a first childhood episode of CNS inflammatory demyelination. AB - Public concern about possible increases in the risk of multiple sclerosis associated with hepatitis B vaccination has led to low vaccination coverage. We investigated whether this vaccination after a first episode of acute CNS inflammatory demyelination in childhood increased the risk of conversion to multiple sclerosis. We studied the French Kid Sclerose en Plaques (KIDSEP) neuropaediatric cohort of patients enrolled between 1994 and 2003 from their first episode of acute CNS inflammatory demyelination (inclusion in the cohort) until the occurrence of a second episode, up to 2005. A Cox proportional hazards model of time-dependent vaccine exposure was used to evaluate the effect of vaccination (hepatitis B, tetanus) during follow-up on the risk of second episode occurrence (conversion to multiple sclerosis). The cohort included 356 subjects with a mean follow-up of 5.8 years (SD 2.7). Relapse occurred in 146 (41%) subjects during follow-up; 33 subjects were exposed to hepatitis B vaccine and 28 to tetanus vaccine at some time during follow-up. The adjusted hazard ratio (HR) for relapse occurring within 3 years of hepatitis B vaccination was 0.78 (0.32 1.89) and during any time period was 1.09 (0.53-2.24). The adjusted HR for relapse occurring within 3 years of tetanus vaccination was 0.99 (0.58-1.67) and during any time period was 1.08 (0.63-1.83). We conclude that vaccination against hepatitis B or tetanus after a first episode of CNS inflammatory demyelination in childhood does not appear to increase the risk of conversion to multiple sclerosis, although the possibility of a small increase in risk cannot be excluded. PMID- 17276997 TI - Microdosimetric analysis for high LET radiation. AB - For short range high linear energy transfer (LET) radiation therapy the biological effects are strongly affected by the heterogeneity of the specific energy (z) distribution delivered to tumour cells. Three-dimensional (3-D) dosimetry information at the cellular level is required for this study. An ideal approach would be the reconstruction of the cell and the radiation source microdistribution from sequential autoradiographic sections, which is, however, not a practical solution. In this paper, a novel microdosimetry analysis method, which obtains the specific energy (z) distribution directly from the morphological information in individual autoradiographic sections, is applied to human glioblastoma multifore (GBM) and normal brain tissue specimens in boron neutron capture therapy. The results are consistent with Monte Carlo simulation and demonstrate a uniform radiation source distribution in both GBM and normal brain tissues. We also hypothesise a biophysical model based on specific energy for survival analysis. The specific energy distributions to cell nuclei were calculated with a uniform radiation source distribution. By combining this microdosimetric analysis with measured cell survival data at the low dose region, a cell survival curve at high doses is predicted, which is consistent with the commonly used simple exponential curve model for high LET radiation. PMID- 17276998 TI - Energy deposition stochastics and track structure: what about the target? AB - The broad field of microdosimetry, as reflected in the proceedings of the 13 previous symposia in this series, has been largely concerned with the microscopic stochastics of energy deposition from ionising radiations of different qualities, the ways in which these can be described and the information that they can provide towards mechanistic understanding of the biological effects of radiation and for practical applications. Directions of the research have been strongly influenced by technical developments at particular times, most notably the tissue equivalent proportional counter and later Monte Carlo track-structure simulation methods. Essential to the research have been evolving notions as to characteristics of the relevant biological targets, and in particular their sizes and structures in relation to the microscopic features of the radiation. Over the decades since the first Symposium on Microdosimetry, in 1967, emphasis has fluctuated from key targets being assumed to be of nanometre dimensions, then up to one micrometer, ten micrometers, and then back again to a few nanometres. Some of these historical threads are traced through the successive symposia, culminating in current emphasis on the predominant importance of clustered damage in DNA, first revealed by track-structure simulations, but tempered by recognition also of the contribution that novel 'non-targeted' effects may play in the overall biological consequences of radiation. PMID- 17276999 TI - Investigation of the neutron energy distribution of the IRSN 241Am-Be(alpha,n) source. AB - The neutron energy distribution of the IRSN standard 241Am-Be(alpha,n) source was measured using a proton recoil liquid scintillator, BC501A, >1.65 MeV. The experimental data were compared with the ISO recommended neutron energy distribution for an Am-Be source and some significant discrepancies were observed. Monte Carlo simulations were then performed to investigate on the neutron source term in order to consider the different parameters between the IRSN Am-Be source and the one used to establish the neutron emission spectrum recommended by the ISO standard. The variation of the parameters of the source did not explain the remaining discrepancies. A good agreement with the experimental results was observed when the theoretical neutron energy distribution from Geiger and Van der Zwan was introduced in the study as new source term. These investigations showed that the ISO recommended Am-Be distribution might not be well suited to represent the neutron energy distribution of all Am-Be sources, and that the manufacturing of the sources might play a major role in the neutron fluence energy distribution. PMID- 17277000 TI - Surgical outcome of stage III and IV adrenocortical carcinoma. AB - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor usually diagnosed at an advanced stage on invasion of or adherence to adjacent organs. We report surgical outcome of stage III and IV ACCs. METHODS: ACCs from seven patients at clinical stage II (n = 1), III (n = 4), or IV (n = 2) were resected. Combined resection of the liver and inferior vena cava was performed in six patients. Morbidity, mortality, recurrence and survival were analyzed. RESULTS: The pathological stage was stage III in five patients and stage IV in two patients. The mortality was zero and the morbidity was two of seven (29%) patients. The estimated 3-year disease-free and overall survivals for stage III were 20% and 40%, respectively, with a median follow-up of 32 months (range, 11-58). The mean disease-free survival was 21.0 +/- 9.0 months (95% CI: 3.3-38.7). The 3-year disease-free and overall survivals for stage III and IV were 14.3% and 28.6%, respectively. The mean disease-free survival time was 18.6 +/- 6.7 months (95% CI: 5.4-31.8). The most frequent site of metastasis was the lungs, seen in four patients, and liver in three patients. Loco-regional, intra-abdominal lymph node, peritoneum, bone, brain recurrences were also seen in one patient each. The mean survival after recurrence was 19.0 +/- 3.3 months (95% CI: 12.6-25.5), and the 50% survival was 18.4 months with mitotan and cytotoxic drug therapy. CONCLUSIONS: Resection for stage III, IV ACCs affords the possibility of negative margins, acceptable peri-operative morbidity and mortality, and prolongs survival in selected patients. PMID- 17277001 TI - Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate. AB - Bisphosphonates reduce the rate of bone resorption and bone remodelling. Given daily, they decrease the risk of fractures in postmenopausal osteoporosis. When bisphosphonates were given at extended drug-free intervals this antifracture efficacy was generally not seen. This may be due to the different pattern of bone remodelling changes. Data from randomised clinical studies of ibandronate, given orally or intravenously, at different doses and for variable time intervals to women with osteoporosis were examined to explore the relationship between intermittent bisphosphonate therapy, changes in bone resorption and fracture risk. The magnitude of the reduction of the rate of bone resorption at the end of the drug-free interval rather than its fluctuation pattern after bisphosphonate administration determines antifracture efficacy, provided that these fluctuations occur within the premenopausal range. Prolongation of the drug-free interval beyond 2 weeks should be compensated by a dose higher than the cumulative daily dose. PMID- 17277002 TI - In vivo evidence for apoptosis in the bone marrow in systemic lupus erythematosus. AB - An increase in leucocyte apoptosis and impaired clearance of apoptotic cells has been observed in patients with systemic lupus erythematosus (SLE). Apoptotic cells are likely to be a key source of autoantigens in SLE as they express many of the nuclear autoantigens (in surface blebs and apoptotic bodies) that are relevant to this disease. The clearance of apoptotic cells is usually a rapid process, such that few cells are usually seen in the extracellular environment in vivo. We report a case in which multiple apoptotic bodies were observed in the bone marrow of a patient with SLE that was complicated by an immune-mediated pancytopenia. We have subsequently examined the frequency of apoptotic cells, identified morphologically, and by caspase-3 staining in bone-marrow trephine samples taken from patients with SLE over a 10-year period of follow-up. A high proportion of bone marrows contained apoptotic debris. The novel demonstration of apoptotic bodies in vivo in patients with SLE is unusual and supports the notion that the marrow may be a target organ in the disease. Their abundance is also consistent with the hypothesis that normal clearance mechanisms are defective and/or overwhelmed in SLE. PMID- 17277003 TI - Investigation of association between the TRAF family genes and RA susceptibility. AB - OBJECTIVE: The tumour necrosis factor (TNF) receptor-associated factor (TRAF) family is important in activating multiple inflammatory and immune related processes induced by cytokines such as TNFalpha and interleukin-1. These genes therefore represent strong candidate susceptibility factors for rheumatoid arthritis (RA). A study was undertaken to investigate the association between single nucleotide polymorphisms (SNPs) spanning six TRAF genes and RA in a British population. METHODS: Twenty-three haplotype tagging (ht) SNPs and 26 random SNPs spanning the six TRAF genes were initially tested for association in a cohort of 351 unrelated patients with RA and 368 controls. Any SNPs demonstrating an association were genotyped in further samples. Sequenom MassARRAY technology was preferentially used for genotyping. Both single point and haplotypic analyses were performed. RESULTS: Forty-four SNPs were successfully genotyped and conformed to Hardy-Weinberg expectation. A single SNP, rs7514863, mapping upstream of the TRAF5 gene and affecting a putative transcription factor binding site, demonstrated a significant association across the entire cohort of 1273 cases with RA compared with 2463 healthy controls (OR for minor T allele 1.2 (95% CI 1.06 to 1.36), p = 0.005). The association was stronger in the subgroup carrying at least one copy of the shared epitope alleles (OR 1.43 (95% CI 1.18 to 1.73), p = 0.0003). CONCLUSION: These findings provide evidence for the association of an SNP upstream of a strong candidate RA susceptibility gene, TRAF5, in a large cohort of patients and controls. Further association and functional studies are required to investigate the role of this variant, or one in linkage disequilibrium with it, in RA disease causation. PMID- 17277005 TI - Development of dedicated STEM with high stability. AB - We developed a dedicated scanning transmission electron microscope with high stability. The mechanical and electronic stabilities of the microscope were substantially improved, e.g. the specimen drift rate was found to be <0.2 nm min( 1). The Fourier transform of an ADF image showed spots of 0.105 nm at an acceleration voltage of 200 kV without spherical aberration corrector. The stabilized STEM instrument allows us to acquire distortion-free STEM images and high-signal to noise ratio analyses. We have shown the outline of the instrument and preliminary results. PMID- 17277004 TI - Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies. AB - OBJECTIVES: The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high-dose intravenous immunoglobulin (IVIG) in inflammatory myopathies by investigating the effects on muscle function and immunological molecules in skeletal muscle of polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) patients. METHODS: Thirteen treatment-resistant patients, 6 PM, 4 DM, 2 IBM and 1 juvenile DM, were treated with 2 g/kg of IVIG, three times at monthly intervals. Functional Index in Myositis and serum creatinine kinase (CK) levels were determined, and muscle biopsies were performed before treatment and after the third IVIG infusion. Immunological molecules were also studied in biopsies taken 24-48 h after the first infusion. RESULTS: Improved muscle function was observed in three patients (1 PM, 1 DM and 1 IBM) and CK levels decreased in five. T cells, macrophages, major histocompatibility complex (MHC) class I antigen on muscle fibres, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and membranolytic attack complex (MAC) deposits on capillaries were present to an equal degree in biopsies before and after IVIG treatment. No correlation between the clinical response and molecular changes was found. CONCLUSIONS: The clinical effects of high-dose IVIG on muscle function in patients with refractory inflammatory active myositis did not correspond to effects on any of the investigated molecules in our study. T cells, macrophages, phenotypical changes in muscle fibres and endothelial cell activation were still present after treatment. These observations question a role for IVIG as an immune modulating therapy in patients with inflammatory myopathies. PMID- 17277006 TI - The creation of a novel fluorescent protein by guided consensus engineering. AB - Consensus engineering has been used to increase the stability of a number of different proteins, either by creating consensus proteins from scratch or by modifying existing proteins so that their sequences more closely match a consensus sequence. In this paper we describe the first application of consensus engineering to the ab initio creation of a novel fluorescent protein. This was based on the alignment of 31 fluorescent proteins with >62% homology to monomeric Azami green (mAG) protein, and used the sequence of mAG to guide amino acid selection at positions of ambiguity. This consensus green protein is extremely well expressed, monomeric and fluorescent with red shifted absorption and emission characteristics compared to mAG. Although slightly less stable than mAG, it is better expressed and brighter under the excitation conditions typically used in single molecule fluorescence spectroscopy or confocal microscopy. This study illustrates the power of consensus engineering to create stable proteins using the subtle information embedded in the alignment of similar proteins and shows that the benefits of this approach may extend beyond stability. PMID- 17277007 TI - Improving quality at the hospital psychiatric ward level through the use of the EFQM model. AB - OBJECTIVE: To describe the implementation of the European Foundation for Quality Management (EFQM) model as a quality framework for improving a psychiatric hospital ward. METHODOGY: Two self-assessments were conducted using the EFQM model. The self-assessment methods combined two approaches proposed by the EFQM: the award simulation approach and the questionnaire approach. Work groups were set up to improve the areas for improvement identified on the self-assessment. RESULTS: The EFQM was a useful framework for self-assessment at the ward level and a good system for identifying areas for improvement. Only one of the 32 sub criteria did not apply at the ward level. The self-assessment score was 209 points in 2003 and 311 points 2 years later (an increase of 48.8% from the initial score). DISCUSSION: The main difficulties were ensuring that clinical personnel understood the EFQM model, the extra effort demanded by the initial phase and the lack of decision-making capacity in certain relevant areas. Adapting the self-assessment methodology to the specific context facilitated the process, as did a high level of involvement of the part of manager and staff. CONCLUSIONS: It is possible to implement the EFQM model at the hospital was level and it has a positive influence on staff communication and involvement. It is important, when working at this level, to adequately focus the scope of the project on improving quality in those areas where there is decision-making capacity. PMID- 17277008 TI - Expectations and received knowledge by surgical patients. AB - OBJECTIVE: Here, the aim is to compare surgical patients' knowledge expectations at admission with the knowledge they received during their hospital stay. DESIGN: The study used a descriptive and comparative design. SETTING: The study was conducted on surgical wards at one randomly selected university hospital in Finland. PARTICIPANTS: The sample (n = 237) consisted of surgical patients (traumatological, gastroenterological, urological and heart and thorax surgery) admitted to hospital during a 2-month period in 2003. METHODS: The data were collected by two specially developed, parallel questionnaires: Hospital Patients' Knowledge Expectations and Hospital Patients' Received Knowledge. These 40-item instruments used a four-tier response scale and made a distinction between the bio-physiological, functional, experiential, ethical, social and financial dimensions of knowledge. The data were analysed statistically. RESULTS: Surgical patients received less knowledge than they felt they expected on the bio physiological, functional, experiential, ethical, social and financial dimensions. Their knowledge expectations and the knowledge they received were related to age, gender and level of basic education. CONCLUSIONS: The results highlighted the need for improved patient education. Surgical patients expect to receive more knowledge than they actually receive on all dimensions. The most problematic areas in the education of surgical patients are the experiential, ethical, social and financial dimensions of knowledge. In particular, younger patients, female patients and patients with a higher level of education require more attention. PMID- 17277009 TI - Patient, carer and staff experience of a hospital-based stroke service. AB - OBJECTIVE: Here, the aim is to study the experiences of patients, carers and staff throughout a hospital stroke care pathway. DESIGN: Focus groups of patients, carers and staff followed a semi-structured format to elucidate experiences. The groups were recorded, transcribed and subjected to thematic analysis. Analyses were verified by researchers and participants. RESULTS: Patients and carers produced four overlapping themes: 'information', 'staff attitudes', 'availability of care/treatment' and 'considering the whole person in context'. The carers' group produced two additional themes: 'accommodation of patients' individual needs' and 'burden of care'. Their experiences were complex and multi-faceted; positive views of the whole service co-existed with negative views of some aspects. The staff groups produced six themes: 'specialist service', 'split service', 'availability of care', 'consistency of care', 'staff morale' and 'wish for change'. Positive views of the specialist service were tempered by problems with physical and professional separation, staff shortages and 'hierarchical practice' that reduced collective decision-making. CONCLUSION: Some of the patients' and carers' perspectives have not been previously reported in the stroke literature, including a desire for individualized treatment, the consideration of wider, non-physical needs and the carers' sense of burden. In addition, the study revealed how staff, carers and patients viewed each other and the service and demonstrated the concordance of their perceptions. However, staff showed little insight into the users' need for information and negative experiences of care. In contrast with previous research, lack of emotional care, poor continuity of care and lack of staff knowledge and skills were not identified as problems. PMID- 17277010 TI - Performance improvement based on integrated quality management models: what evidence do we have? A systematic literature review. AB - PURPOSE: Health care organizations have to improve their performance for multiple stakeholders and organize integrated care. To facilitate this, various integrated quality management models can be used. This article reviews the literature on the Malcolm Baldrige Quality Award (MBQA) criteria, the European Foundation Quality Management (EFQM) Excellence model (Excellence award models) and the Chronic Care Model. The focus is on the empirical evidence for improved performance by the implementation of interventions based on these models. DATA SOURCES: A systematic literature review from 1995 to May 2006 in the Pubmed, Cochrane, and ABI- databases was conducted. STUDY SELECTION: After selection, 37 studies were included, 16 in the Excellence award model search and 21 in the Chronic Care Model search. DATA EXTRACTION AND RESULTS OF ANALYSIS: Data were retrieved about the main intervention elements, study design, evidence level, setting and context factors, data collection and analysis, principal results and performance dimensions. No Excellence Award model studies with controlled designs were found. For the Chronic Care Model, one systematic review, one meta analysis and six controlled studies were included. Seventeen studies (2 in Excellence award model, 15 in Chronic Care Model) reported one or more significant results. CONCLUSION: There is some evidence that implementing interventions based on the 'evidence based developed' Chronic Care Model may improve process or outcome performances. The evidence for performance improvement by interventions based on the 'expert based developed' MBQA criteria and the EFQM Excellence model is more limited. Only a few studies include balanced measures on multiple performance dimensions. Considering the need for integrated care and chronic care improvement, the further development of these models for guiding improvements in integrated care settings and their specific context factors is suggested. PMID- 17277011 TI - Improving adherence to family planning guidelines in Kenya: an experiment. AB - QUALITY PROBLEM: Research in Kenya in the mid-1990s suggested poor quality family planning services and limited access to services. Clinical guidelines for family planning and reproductive health were published in 1991 and updated in 1997, but never widely distributed. CHOICE OF SOLUTION: Managers and trainers chose intensive, district-level training workshops to disseminate guidelines and update health workers on guideline content and best practices. INTERVENTION: Training workshops were held in 41 districts in 1999. Trainees were instructed to update their untrained co-workers afterwards. As a reinforcement, providers in randomly selected areas received a 'cascade training package' of instructional materials and training tips. Providers in 15 randomly selected clinics also received 'supportive supervision' visits as a second reinforcement. EVALUATION METHODOLOGY: A cluster-randomized experiment in 72 clinics assessed the overall impact of the training and the marginal benefits of the two reinforcing activities. Researchers and trainers created several dozen indicators of provider knowledge, attitudes, beliefs and practices. Binomial and multivariate analyses were used to compare changes over time in indicators and in aggregated summary scores. Data from patient interviews were analysed to corroborate provider practice self-reports. Cost data were collected for an economic evaluation. RESULTS: Post-test data collected in 2000 showed that quality of care and access increased after the intervention. The cascade training package showed less impact than supportive supervision, but the former was more cost-effective. LESSONS LEARNED: Service delivery guidelines, when properly disseminated, can improve family planning practices in sub-Saharan Africa. PMID- 17277012 TI - Does setting adolescent-friendly standards improve the quality of care in clinics? Evidence from South Africa. AB - OBJECTIVE: To determine whether setting and implementing adolescent-friendly standards improves the quality of adolescent services in clinics. DESIGN: The evaluation used a quasi-experimental case-control design. SETTING/PARTICIPANTS: Eleven public health clinics involved in the adolescent-friendly program [The National Adolescent Friendly Clinic Initiative (NAFCI)] and 11 control clinics. INTERVENTION: This included implementation of a set of 10 adolescent-friendly standards and 41 corresponding criteria. MAIN OUTCOME MEASURES: Percentage scores were achieved for each standard and criterion. Clinics were awarded a Gold Star if they achieved an overall clinic score (average standard score) of >or=90%, a Silver Star for a score between 60 and 89% and a Bronze Star for a score between 30 and 59%. RESULTS: The NAFCI clinics performed better than the control clinics on most criteria. The combined average overall clinic score of all the NAFCI clinics (79.9%) was significantly higher (P = 0.005) than the overall score for the control group clinics (60.9%). Results showed that the longer NAFCI was implemented at a clinic, the higher the score and the more likely that clinic would be accredited as an 'adolescent friendly' clinic. NAFCI clinics performed significantly better than the control clinics on criteria specific to the provision of adolescent-friendly services including knowledge of adolescent rights and non-judgmental attitudes of staff. CONCLUSION: Setting and implementing standards and criteria improves the quality of adolescent services in clinics. The standards and criteria should be set on the basis of the characteristics of adolescent-friendly services and quality of care indicators. Best results are achieved when a facilitator trained in quality improvement methodologies supports clinics. PMID- 17277013 TI - Language proficiency and adverse events in US hospitals: a pilot study. AB - OBJECTIVE: To examine differences in the characteristics of adverse events between English speaking patients and patients with limited English proficiency in US hospitals. SETTING: Six Joint Commission accredited hospitals in the USA. METHOD: Adverse event data on English speaking patients and patients with limited English proficiency were collected from six hospitals over 7 months in 2005 and classified using the National Quality Forum endorsed Patient Safety Event Taxonomy. RESULTS: About 49.1% of limited English proficient patient adverse events involved some physical harm whereas only 29.5% of adverse events for patients who speak English resulted in physical harm. Of those adverse events resulting in physical harm, 46.8% of the limited English proficient patient adverse events had a level of harm ranging from moderate temporary harm to death, compared with 24.4% of English speaking patient adverse events. The adverse events that occurred to limited English proficient patients were also more likely to be the result of communication errors (52.4%) than adverse events for English speaking patients (35.9%). CONCLUSIONS: Language barriers appear to increase the risks to patient safety. It is important for patients with language barriers to have ready access to competent language services. Providers need to collect reliable language data at the patient point of entry and document the language services provided during the patient-provider encounter. PMID- 17277014 TI - Sex ratio and time to pregnancy: analysis of four large European population surveys. AB - OBJECTIVE: To test whether the secondary sex ratio (proportion of male births) is associated with time to pregnancy, a marker of fertility. Design Analysis of four large population surveys. Setting Denmark and the United Kingdom. Participants 49 506 pregnancies. MAIN OUTCOME MEASURE: Secondary sex ratio. RESULTS: No association was found between the sex ratio and time to pregnancy and no discernible trend was found for sex ratio with time to pregnancy, either within individual datasets or in the pooled analysis. The odds ratios were 0.97 (95% confidence interval 0.90 to 1.04) for contraceptive failures, 1.01 (0.96 to 1.05) for time to pregnancy of 2-4 months, 1.02 (0.97 to 1.08) for 5-10 months, 0.98 (0.93 to 1.03) for 11 months or more, and 0.88 (0.74 to 1.06) for fertility treatment, with 0-1 months as the reference category. CONCLUSION: No association was found between the secondary sex ratio and time to pregnancy. PMID- 17277015 TI - Macromolecular transport in heart valves. I. Studies of rat valves with horseradish peroxidase. AB - The present study aims to experimentally elucidate subtle structural features of the rat valve leaflet and the related nature of macromolecular transport across its endothelium and in its subendothelial space, information necessary to construct a rational theoretical model that can explain observation. After intravenous injection of horseradish peroxidase (HRP), we perfusion-fixed the aortic valve of normal Sprague-Dawley rats and found under light microscopy that HRP leaked through the leaflet's endothelium at very few localized brown spots, rather than uniformly. These spots grew nearly as rapidly with HRP circulation time before euthanasia as aortic spots, particularly when the time axis only included the time the valve was closed. These results suggest that macromolecular transport in heart valves depends not only on the direction normal to, but also parallel to, the endothelial surface and that convection, as well as molecular diffusion, plays an important role in macromolecular transport in heart valves. Transmission electron microscopy of traverse leaflet sections after 4-min HRP circulation showed a very thin ( approximately 150 nm), sparse layer immediately beneath the endothelium where the HRP concentration was much higher than that in the matrix below it. Nievelstein-Post et al.'s (Nievelstein-Post P, Mottino G, Fogelman A, Frank J. Arterioscler Thromb 14: 1151-1161, 1994) ultrarapid freezing/rotary shadow etching of the normal rabbit valve's subendothelial space supports the existence of this very thin, very sparse "valvular subendothelial intima," in analogy to the vascular subendothelial intima. PMID- 17277016 TI - Endogenous RGS proteins modulate SA and AV nodal functions in isolated heart: implications for sick sinus syndrome and AV block. AB - G protein-coupled receptors play a pivotal role in regulating cardiac automaticity. Their function is controlled by regulator of G protein signaling (RGS) proteins acting as GTPase-activating proteins for Galpha subunits to suppress Galpha(i) and Galpha(q) signaling. Using knock-in mice in which Galpha(i2)-RGS binding and negative regulation are disrupted by a genomic Galpha(i2)G184S (GS) point mutation, we recently (Fu Y, Huang X, Zhong H, Mortensen RM, D'Alecy LG, Neubig RR. Circ Res 98: 659-666, 2006) showed that endogenous RGS proteins suppress muscarinic receptor-mediated bradycardia. To determine whether this was due to direct regulation of cardiac pacemakers or to alterations in the central nervous system or vascular responses, we examined isolated, perfused hearts. Isoproterenol-stimulated beating rates of heterozygote (+/GS) and homozygote (GS/GS) hearts were significantly more sensitive to inhibition by carbachol than were those of wild type (+/+). Even greater effects were seen in the absence of isoproterenol; the potency of muscarinic-mediated bradycardia was enhanced fivefold in GS/GS and twofold in +/GS hearts compared with +/+. A(1)-adenosine receptor-mediated bradycardia was unaffected. In addition to effects on the sinoatrial node, +/GS and GS/GS hearts show significantly increased carbachol-induced third-degree atrioventricular (AV) block. Atrial pacing studies demonstrated an increased PR interval and AV effective refractory period in GS/GS hearts compared with +/+. Thus loss of the inhibitory action of endogenous RGS proteins on Galpha(i2) potentiates muscarinic inhibition of cardiac automaticity and conduction. The severe carbachol-induced sinus bradycardia in Galpha(i2)G184S mice suggests a possible role for alterations of Galpha(i2) or RGS proteins in sick sinus syndrome and pathological AV block. PMID- 17277018 TI - The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment. AB - Recent clinical and animal studies have shown that collateral artery growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin-converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the ANG II type 1 receptor. After ileal artery ligation, mesenteric collateral growth did not occur in untreated, young, spontaneously hypertensive rats. Significant luminal expansion occurred in collaterals of spontaneously hypertensive rats treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the ACEI captopril, but not ANG II type 1 (losartan) or type 2 (PD-123319) receptor blockers. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its antioxidant properties. RT-PCR demonstrated that ANG II type 1 receptor and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral artery growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals. PMID- 17277017 TI - Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents. AB - Alternans of cardiac repolarization is associated with arrhythmias and sudden death. At the cellular level, alternans involves beat-to-beat oscillation of the action potential (AP) and possibly Ca(2+) transient (CaT). Because of experimental difficulty in independently controlling the Ca(2+) and electrical subsystems, mathematical modeling provides additional insights into mechanisms and causality. Pacing protocols were conducted in a canine ventricular myocyte model with the following results: 1) CaT alternans results from refractoriness of the sarcoplasmic reticulum Ca(2+) release system; alternation of the L-type calcium current has a negligible effect; 2) CaT-AP coupling during late AP occurs through the sodium-calcium exchanger and underlies AP duration (APD) alternans; 3) increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity extends the range of CaT and APD alternans to slower frequencies and increases alternans magnitude; its decrease suppresses CaT and APD alternans, exerting an antiarrhythmic effect; and 4) increase of the rapid delayed rectifier current (I(Kr)) also suppresses APD alternans but without suppressing CaT alternans. Thus CaMKII inhibition eliminates APD alternans by eliminating its cause (CaT alternans) while I(Kr) enhancement does so by weakening CaT-APD coupling. The simulations identify combined CaMKII inhibition and I(Kr) enhancement as a possible antiarrhythmic intervention. PMID- 17277019 TI - Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model. AB - The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers. PMID- 17277020 TI - Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin. AB - We assessed whether aspirin (acetylsalicylic acid, ASA), administered before reperfusion, abrogates the infarct size (IS)-limiting effect of atorvastatin (ATV). Statins reduce IS. This dose-dependent effect is mediated by upregulation of cycloxygenase-2 (COX2) and PGI(2) production. Administration of selective COX2 inhibitors either with ATV for 3 days or immediately before coronary occlusion blocks the IS-limiting effect of ATV. Sprague-Dawley rats received 3-day ATV (10 mg x kg(-1) x day(-1)) or water alone. Rats underwent 30 min coronary artery occlusion and 4 h reperfusion (IS protocol, n=8 in each group), or rats underwent 30 min coronary artery occlusion and 10 min reperfusion (enzyme expression and activity protocol, n=4 in each group). Immediately before reperfusion rats received intravenous ASA (5, 10, or 20 mg/kg) or saline. Area-at-risk (AR) was assessed by blue dye and IS by triphenyltetrazolium chloride. ATV reduced IS (10.1 +/- 1.4% of the AR) compared with controls (31.0 +/- 2.2%). Intravenous ASA alone did not affect IS (29.0 +/- 2.6%); however, ASA dose dependently (5, 10, and 20 mg/kg) attenuated the protective effect of ATV on IS (15.8 +/- 0.9%, 22.0 +/- 1.6%, and 23.7 +/- 3.8%, respectively). ASA dose dependently blocked the upregulation of COX2 by ATV. COX2 activity was as follows: control, 8.93 +/- 0.90 pg/mg; ATV, 75.85 +/- 1.08 pg/mg; ATV + ASA5, 34.39 +/- 1.48 pg/mg; ATV + ASA10, 19.87 +/- 1.10 pg/mg; and ATV + ASA20, 9.36 +/- 0.94 pg/mg. ASA, administered before reperfusion in doses comparable to those used in the clinical setting, abrogates the IS-limiting effect of ATV in a model with mechanical occlusion of the coronary artery. This potential adverse interaction should be further investigated in the clinical setting of acute coronary syndromes. PMID- 17277021 TI - Activators of the PKA and PKG pathways attenuate RhoA-mediated suppression of the KDR current in cerebral arteries. AB - This study tested whether activation of protein kinase A (PKA) and G (PKG) pathways would attenuate the ability of RhoA to suppress the delayed rectifier K(+) (K(DR)) current and limit agonist-induced depolarization and constriction. Smooth muscle cells from rat cerebral arteries were enzymatically isolated, and whole cell K(DR) currents were monitored with conventional patch-clamp electrophysiology. The K(DR) current averaged 21.2 +/- 2.3 pA/pF (mean +/- SE) at +40 mV and was potently inhibited by UTP. Current suppression was eliminated in the presence of C3 exoenzyme, confirming that this modulation is dependent on RhoA. Activation of PKA (dibutyryl-cAMP, forskolin) or PKG (dibutyryl-cGMP, sodium nitroprusside, nitric oxide) similarly abolished the ability of UTP to suppress K(DR) and did so without effect on baseline current. Using pressure myography techniques, we stripped cerebral arteries of endothelium and preconstricted them with UTP; these were subsequently shown to hyperpolarize and dilate to both forskolin and sodium nitroprusside. An increase in K(V) channel activity was found to partly underlie these associated changes, as constriction to 4-aminopyridine (K(DR) channel blocker) was greater after PKA or PKG activation. We conclude from our electrophysiological and functional observations that the PKA and PKG pathways attenuate the ability of UTP to depolarize and constrict cerebral arteries in part by minimizing the RhoA-mediated suppression of the K(DR) current. PMID- 17277022 TI - PTEN reduces cuff-induced neointima formation and proinflammatory cytokines. AB - An inflammatory response followed by vascular injury plays an important role in neointima formation and development of atherosclerotic lesions, which are in part mediated by proinflammatory cytokines. Using a cuff injury model, we examined the effects of adenovirus-mediated overexpression of phosphatase and tensin homology deleted on chromosome 10 (PTEN) on neointima formation and the proinflammatory response. A cuff was placed around the femoral artery, and adenovirus expressing human PTEN type 1 (AdPTEN) or Escherichia coli beta-galactosidase (AdLacZ) was injected between the cuff and the adventitia. After 14 days, the arteries were examined histopathologically and by Western blotting. The significant reduction of neointima formation by AdPTEN compared with AdLacZ was accompanied by reduced cell proliferation and increased adventitial cell apoptosis. AdPTEN also reduced expression of phosphorylated I kappa B-alpha, but not nonphosphorylated I kappa B alpha. Western blotting revealed that AdPTEN reduced the cuff injury-induced expression levels of monocyte chemoattractant protein-1, TNF-alpha, and IL-1 beta and their expression in all layers of the arterial wall. In contrast, cuff induced macrophage invasion, which was also inhibited by AdPTEN, was detected only at the intimal surface and in the adventitia. In cultured vascular smooth muscle cells, PTEN directly inhibited ANG II-induced monocyte chemoattractant protein-1 expression as quantified by real-time PCR and Western blotting. Our results suggest that overexpression of PTEN reduces neointima formation, possibly in part through inhibition of the inflammatory response by macrophage invasion and proinflammatory cytokine expression. PMID- 17277023 TI - Speckle-tracking echocardiography correctly identifies segmental left ventricular dysfunction induced by scarring in a rat model of myocardial infarction. AB - Speckle-tracking echocardiography (STE) uses a two-dimensional echocardiographic image to estimate two orthogonal strain components. The aim of this study was to assess sensitivity of circumferential (S(circ)) and radial (S(rad)) strains to infarct-induced left ventricular (LV) remodeling and scarring of the LV in a rat. To assess the relationship among S(circ), S(rad), and scar size, two-dimensional echocardiographic LV short-axis images (12 MHz transducer, Vivid 7 echo machine) were collected in 34 Lewis rats 4 to 10 wk after ligation of the left anterior descending artery. Percent segmental fibrosis was assessed from histological LV cross sections stained by Masson trichrome. Ten normal rats served as echocardiographic controls. S(circ) and S(rad) were assessed by STE. Histological data showed consistent scarring of anterior and lateral segments with variable extension to posterior and inferior segments. Both S(circ) and S(rad) significantly decreased after myocardial infarction (P<0.0001 for both). As anticipated, S(circ) and S(rad) were lowest in the infarcted segments. Multiple linear regression showed that segmental S(circ) were similarly dependent on segmental fibrosis and end-systolic diameter (P<0.0001 for both), whereas segmental S(rad) measurements were more dependent on end-systolic diameter (P<0.0001) than on percent fibrosis (P<0.002). STE correctly identifies segmental LV dysfunction induced by scarring that follows myocardial infarction in rats. PMID- 17277024 TI - Redox regulation of ischemic preconditioning is mediated by the differential activation of caveolins and their association with eNOS and GLUT-4. AB - Reactive oxygen species (ROS) generated during ischemia-reperfusion (I/R) enhance myocardial injury, but brief periods of myocardial ischemia followed by reperfusion [ischemic preconditioning (IP)] induce cardioprotection. Ischemia is reported to stimulate glucose uptake through the translocation of GLUT-4 from the intracellular vesicles to the sarcolemma. In the present study we demonstrated involvement of ROS in IP-mediated GLUT-4 translocation along with increased expression of caveolin (Cav)-3, phospho (p)-endothelial nitric oxide synthase (eNOS), p-Akt, and decreased expression of Cav-1. The rats were divided into the following groups: 1) control sham, 2) N-acetyl-L-cysteine (NAC, free radical scavenger) sham (NS), 3) I/R, 4) IP + I/R (IP), and 5) NAC + IP (IPN). IP was performed by four cycles of 4 min of ischemia and 4 min of reperfusion followed by 30 min of ischemia and 3, 24, 48 h of reperfusion, depending on the protocol. Increased mRNA expression of GLUT-4 and Cav-3 was observed after 3 h of reperfusion in the IP group compared with other groups. IP increased expression of GLUT-4, Cav-3, and p-AKT and p-eNOS compared with I/R. Coimmunoprecipitation demonstrated decreased association of Cav-1/eNOS in the IP group compared with the I/R group. Significant GLUT-4 and Cav-3 association was also observed in the IP group. This association was disrupted when NAC was used in conjunction with IP. It clearly documents a significant role of ROS signaling in Akt/eNOS/Cav-3 mediated GLUT-4 translocation and association in IP myocardium. In conclusion, we demonstrated a novel redox mechanism in IP-induced eNOS and GLUT-4 translocation and the role of caveolar paradox in making the heart euglycemic during the process of ischemia, leading to myocardial protection in a clinically relevant rat ischemic model. PMID- 17277025 TI - Wave intensity analysis of left ventricular filling: application of windkessel theory. AB - We extend our recently published windkessel-wave interpretation of vascular function to the wave intensity analysis (WIA) of left ventricular (LV) filling dynamics by separating the pressure changes due to the windkessel from those due to traveling waves. With the use of LV compliance, the change in pressure due solely to LV volume changes (windkessel pressure) can be isolated. Inasmuch as the pressure measured in the cardiovascular system is the sum of its windkessel and wave components (excess pressure), it can be substituted into WIA, yielding the isolated wave effects on LV filling. Our study of six open-chest dogs demonstrated that once the windkessel effects are removed from WIA, the energy of diastolic suction is 2.6 times greater than we previously calculated. Volume related changes in pressure (i.e., the windkessel or reservoir effect) must be considered first when wave motion is analyzed. PMID- 17277026 TI - Mechanoelectric feedback leads to conduction slowing and block in acutely dilated atria: a modeling study of cardiac electromechanics. AB - Atrial fibrillation, a common cardiac arrhythmia, is promoted by atrial dilatation. Acute atrial dilatation may play a role in atrial arrhythmogenesis through mechanoelectric feedback. In experimental studies, conduction slowing and block have been observed in acutely dilated atria. In the present study, the influence of the stretch-activated current (I(sac)) on impulse propagation is investigated by means of computer simulations. Homogeneous and inhomogeneous atrial tissues are modeled by cardiac fibers composed of segments that are electrically and mechanically coupled. Active force is related to free Ca(2+) concentration and sarcomere length. Simulations of homogeneous and inhomogeneous cardiac fibers have been performed to quantify the relation between conduction velocity and I(sac) under stretch. In our model, conduction slowing and block are related to the amount of stretch and are enhanced by contraction of early activated segments. Conduction block can be unidirectional in an inhomogeneous fiber and is promoted by a shorter stimulation interval. Slowing of conduction is explained by inactivation of Na(+) channels and a lower maximum upstroke velocity due to a depolarized resting membrane potential. Conduction block at shorter stimulation intervals is explained by a longer effective refractory period under stretch. Our observations are in agreement with experimental results and explain the large differences in intra-atrial conduction, as well as the increased inducibility of atrial fibrillation in acutely dilated atria. PMID- 17277027 TI - Erythrocyte-associated transients in capillary PO2: an isovolemic hemodilution study in the rat spinotrapezius muscle. AB - Mathematical simulations of oxygen delivery to tissue from capillaries that take into account the particulate nature of blood flow predict the existence of oxygen tension (Po(2)) gradients between erythrocytes (RBCs). As RBCs and plasma alternately pass an observation point, these gradients are manifested as rapid fluctuations in Po(2), also known as erythrocyte-associated transients (EATs). The impact of hemodilution on EATs and oxygen delivery at the capillary level of the microcirculation has yet to be elucidated. Therefore, in the present study, phosphorescence quenching microscopy was used to measure EATs and Po(2) in capillaries of the rat spinotrapezius muscle at the following systemic hematocrits (Hct(sys)): normal (39%) and after moderate (HES1; 27%) or severe (HES2; 15%) isovolemic hemodilution using a 6% hetastarch solution. A 532-nm laser, generating 10-micros pulses concentrated onto a 0.9-microm spot, was used to obtain plasma Po(2) values 100 times/s at points along surface capillaries of the muscle. Mean capillary Po(2) (Pc(O(2)); means +/- SE) significantly decreased between conditions (normal: 56 +/- 2 mmHg, n = 45; HES1: 47 +/- 2 mmHg, n = 62; HES2: 27 +/- 2 mmHg, n = 52, where n = capillary number). In addition, the magnitude of Po(2) transients (DeltaPo(2)) significantly decreased with hemodilution (normal: 19 +/- 1 mmHg, n = 45; HES1: 11 +/- 1 mmHg, n = 62; HES2: 6 +/- 1 mmHg, n = 52). Results suggest that the decrease in Pc(O(2)) and DeltaPo(2) with hemodilution is primarily dependent on Hct(sys) and subsequent microvascular compensations. PMID- 17277028 TI - Short-term pretreatment with low-dose hydrogen peroxide enhances the efficacy of bone marrow cells for therapeutic angiogenesis. AB - Therapeutic angiogenesis can be induced by the implantation of bone marrow cells (BMCs). Hydrogen peroxide (H(2)O(2)) has been shown to increase VEGF expression and to be involved in angiogenesis. We tested the hypothesis that pretreatment with H(2)O(2) enhances the efficacy of BMCs for neovascularization. H(2)O(2) pretreatment was done by incubating mouse BMCs in 5 microM H(2)O(2) for 30 min, followed by washing twice with PBS. The H(2)O(2)-pretreated and untreated BMCs were then studied in vitro and in vivo. RT-PCR analysis showed that expression of VEGF and Flk-1 mRNA was significantly higher in H(2)O(2)-pretreated BMCs than in untreated BMCs after 12 and 24 h of culture (P<0.01). Pretreatment with H(2)O(2) also effectively enhanced the VEGF production and endothelial differentiation from BMCs after 1 and 7 days of culture (P<0.05). To estimate the angiogenic potency in vivo, H(2)O(2)-pretreated or untreated BMCs were intramuscularly implanted into the ischemic hindlimbs of mice. After 14 days of treatment, many of the H(2)O(2)-pretreated BMCs were viable, showed endothelial differentiation, and were incorporated in microvessels. Conversely, the survival and incorporation of the untreated BMCs were relatively poor. Microvessel density and blood flow in the ischemic hindlimbs were significantly greater in the mice implanted with H(2)O(2)-pretreated BMCs than in those implanted with untreated BMCs (P<0.05). These results show that the short-term pretreatment of BMCs with low-dose H(2)O(2) is a novel, simple, and feasible method of enhancing their angiogenic potency. PMID- 17277029 TI - Endothelial function across an oral contraceptive cycle in women using levonorgestrel and ethinyl estradiol. AB - Oral contraceptive pills (OCPs) are a popular contraception method. Currently, lower-dose ethinyl estradiol formulations are most commonly prescribed, although they have been linked to increased arterial vascular risk. The aim of this study was to investigate endothelial function in healthy young women using lower-dose ethinyl estradiol OCPs. We examined flow-mediated, endothelium-dependent and nitroglycerin-mediated, endothelium-independent vasodilation of the brachial artery, comparing two doses of ethinyl estradiol/levonorgestrel OCPs in 15 healthy young women on two study days: once during the active phase and once during the placebo phase of an OCP cycle. Group low dose (LD) (n=7) active pills contained 150 microg levonorgestrel/30 microg ethinyl estradiol versus Group very low dose (VLD) (n=8) with 100 microg levonorgestrel/20 microg ethinyl estradiol. Endothelium-dependent vasodilation was lower during the active phase in Group VLD (5.33 +/- 1.77% vs. 7.23 +/- 2.60%; P=0.024). This phase difference was not observed in Group LD (8.00 +/- 0.970% vs. 7.61 +/- 1.07%; P=0.647). Endothelium independent vasodilation did not differ between phases in either group. Finally, we measured endothelium-dependent vasodilation in two additional women who received 10 microg of unopposed ethinyl estradiol. Endothelium-dependent vasodilation was increased by unopposed ethinyl estradiol compared with the placebo phase (10.88 +/- 2.34% vs. 6.97 +/- 1.83%). These results suggest that levonorgestrel may antagonize the activity of ethinyl estradiol. Thus both the progestin type and estradiol dose need to be considered when assessing arterial vascular risk of OCP use in women. PMID- 17277030 TI - Endothelial senescence after high-cholesterol, high-fat diet challenge in baboons. AB - Increasing evidence indicates that replicative senescence and premature endothelial senescence could contribute to endothelial dysfunction. This study aims at testing the hypothesis that a high-fat diet may lead to premature vascular endothelial senescence in a nonhuman primate model. We isolated endothelial cells from left and right femoral arteries in 10 baboons before and after a 7-wk high-fat dietary treatment. We compared the morphological alterations, replicative capacities, and senescence-associated beta-galactosidase activities (SA-beta-gal) at these two time points. We found that high-fat diet increased the prevalence of endothelial senescence. Endothelial replicative capacities declined dramatically, and SA-beta-gal activities increased significantly in postdietary challenge. There was no change in telomeric length using quantitative flow fluorescence in situ hybridization analysis, suggesting that some stressors lead to cell senescence independent of telomere dysfunction. Our findings that high-fat diet causes endothelial damage through the premature senescence suggest a novel mechanism for the diet-induced endothelial dysfunction. PMID- 17277031 TI - Role of L-type calcium channels and PKC in active tone development in rabbit coronary artery. AB - The present study investigated active tone development in isolated ring segments of rabbit epicardial coronary artery. Endothelium-denuded (E-) or endothelium intact (E+) vessels treated with the NO synthase inhibitor N(omega)-nitro-L arginine (100 microM) developed active tone, which was enhanced by stretch and reversed by the NO donor sodium nitroprusside (SNP; IC(50)=9 nM). Nifedipine abolished active tone and the contractile response to phorbol dibutyrate (PDBu; 10 nM) with the same potency (IC(50)=8 nM), whereas 300 nM PDBu responses were only partially blocked by nifedipine. The classical and novel PKC inhibitors GF 109203X (IC(50)=1-2 microM) and chelerythrine (IC(50)=4-5 microM) and the classical PKC inhibitor Go-6976 (IC(50)=0.3-0.4 microM) blocked both active tone and 10 nM PDBu responses with similar potency. Active tone development was associated with depolarization of membrane potential (E(m)) and a shift to the left of the E(m)-vs.-contraction relationship determined by varying extracellular potassium. The depolarization and leftward shift were reversed by either chelerythrine (10 microM) or SNP (30 nM). PDBu (100-300 nM) increased peak L-type calcium channel (Ca(v)) currents in isolated coronary myocytes, and this effect was reversed by chelerythrine (1 microM) or Go-6976 (200 nM). SNP (500 nM) reduced Ca(v) currents only in the presence of the PKA blocker 8-bromo-2'-O monobutyryl-cAMPS, Rp isomer (10 microM). In conclusion, active tone development in coronary artery is suppressed by basal NO release and is dependent on both enhanced Ca(v) activity and classical PKC activity. Both E(m)-dependent and independent processes contribute to contraction. Our results suggest that one E(m)-independent process is direct enhancement of Ca(v) current by PKC. PMID- 17277032 TI - Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise. AB - Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/ 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS ( 2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS ( 0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS. PMID- 17277033 TI - Carotid intima-media thickness and coronary atherosclerosis: weak or strong relations? AB - AIMS: Measurement of change in carotid intima-media thickness (CIMT) has been proposed as an alternative for the occurrence of cardiovascular (CV) events in the assessment of therapeutic interventions. Nevertheless, criticism has been voiced based on observations indicating a weak relation between CIMT and coronary atherosclerosis as well as on the virtual absence of data showing that progression of CIMT indeed predicts coronary artery disease (CAD) and stroke. METHODS AND RESULTS: We set out to review the evidence on these issues by performing a literature search on these topics. Of the 34 studies on the relation of CIMT with coronary atherosclerosis, as assessed by angiography (n=33) or intravascular ultrasound (n=1), 30 showed a modest positive relationship; the magnitude of which was similar to that found in autopsy studies. Of all studies on CIMT and future CV events (n=18), 17 showed graded positive relationships. At present, only one study has provided evidence on the relation of change in CIMT and future CV events, showing an increased risk with CIMT progression. The paucity of data on progression and future CV risk is partly attributable to time windows required to complete these studies. CONCLUSION: The modest relation between CIMT and coronary atherosclerosis most likely reflects variability in atherosclerosis development between the vascular beds rather than limitations of CIMT measurements. Additional data on the relation between change in CIMT and future CV events is required and currently is in progress. PMID- 17277034 TI - Stent treatment of coronary artery bifurcation lesions. PMID- 17277036 TI - Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. AB - OBJECTIVE: We sought to evaluate the efficacy and safety of vildagliptin, a new dipeptidyl peptidase-4 inhibitor, added to metformin during 24 weeks of treatment in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a double blind, randomized, multicenter, parallel group study of a 24-week treatment with 50 mg vildagliptin daily (n = 177), 100 mg vildagliptin daily (n = 185), or placebo (n = 182) in patients continuing a stable metformin dose regimen (> or =1,500 mg/day) but achieving inadequate glycemic control (A1C 7.5-11%). RESULTS: The between-treatment difference (vildagliptin-placebo) in adjusted mean change (AMDelta) +/- SE in A1C from baseline to end point was -0.7 +/- 0.1% (P < 0.001) and -1.1 +/- 0.1% (P < 0.001) in patients receiving 50 or 100 mg vildagliptin daily, respectively. The between-treatment difference in the AMDelta fasting plasma glucose (FPG) was -0.8 +/- 0.3 mmol/l (P = 0.003) and -1.7 +/- 0.3 mmol/l (P < 0.001) in patients receiving 50 or 100 mg vildagliptin daily, respectively. Adverse events (AEs) were reported by 63.3, 65.0, and 63.5% of patients receiving 50 mg vildagliptin daily, 100 mg vildagliptin daily, or placebo, respectively. Gastrointestinal AEs were reported by 9.6 (P = 0.022 vs. placebo), 14.8, and 18.2% of patients receiving 50 mg vildagliptin daily, 100 mg vildagliptin daily, or placebo, respectively. One patient in each treatment group experienced one mild hypoglycemic event. CONCLUSIONS: Vildagliptin is well tolerated and produces clinically meaningful, dose-related decreases in A1C and FPG as add-on therapy in patients with type 2 diabetes inadequately controlled by metformin. PMID- 17277035 TI - Lack of respiratory chain complex I impairs alternative oxidase engagement and modulates redox signaling during elicitor-induced cell death in tobacco. AB - Alternative oxidase (AOX) functions in stress resistance by preventing accumulation of reactive oxygen species (ROS), but little is known about in vivo partitioning of electron flow between AOX and the cytochrome pathway. We investigated the relationships between AOX expression and in vivo activity in Nicotiana sylvestris and the complex I-deficient CMSII mutant in response to a cell death elicitor. While a specific AOX1 isoform in the active reduced state was constitutively overexpressed in CMSII, partitioning through the alternative pathway was similar to the wild type. Lack of correlation between AOX content and activity indicates severe metabolic constraints in nonstressed mutant leaves. The bacterial elicitor harpin N(Ea) induced similar timing and extent of cell death and a twofold respiratory burst in both genotypes with little change in AOX amounts. However, partitioning to AOX was increased twofold in the wild type but remained unchanged in CMSII. Oxidative phosphorylation modeling indicated a twofold ATP increase in both genotypes. By contrast, mitochondrial superoxide dismutase activity and reduced forms of ascorbate and glutathione were higher in CMSII than in the wild type. These results demonstrate genetically programmed flexibility of plant respiratory routes and antioxidants in response to elicitors and suggest that sustained ATP production, rather than AOX activity by itself or mitochondrial ROS, might be important for in planta cell death. PMID- 17277037 TI - Significance of endothelial progenitor cells in subjects with diabetes. PMID- 17277038 TI - Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. AB - OBJECTIVE: To determine the prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic population and to compare the prevalence of cardiovascular disease (CVD) and its risk factors between people with and without NAFLD. RESEARCH DESIGN AND METHODS: The entire sample of type 2 diabetic outpatients (n = 2,839) who regularly attended our clinic was screened. Main outcome measures were NAFLD (by patient history and liver ultrasound) and manifest CVD (by patient history, review of patient records, electrocardiogram, and echo-Doppler scanning of carotid and lower limb arteries). RESULTS: The unadjusted prevalence of NAFLD was 69.5% among participants, and NAFLD was the most common cause (81.5%) of hepatic steatosis on ultrasound examination. The prevalence of NAFLD increased with age (65.4% among participants aged 40-59 years and 74.6% among those aged > or = 60 years; P < 0.001) and the age-adjusted prevalence of NAFLD was 71.1% in men and 68% in women. NAFLD patients had remarkably (P < 0.001) higher age and sex-adjusted prevalences of coronary (26.6 vs. 18.3%), cerebrovascular (20.0 vs. 13.3%), and peripheral (15.4 vs. 10.0%) vascular disease than their counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with prevalent CVD independent of classical risk factors, glycemic control, medications, and metabolic syndrome features. CONCLUSIONS: NAFLD is extremely common in people with type 2 diabetes and is associated with a higher prevalence of CVD. Follow-up studies are needed to determine whether NAFLD predicts the development and progression of CVD. PMID- 17277039 TI - Influence of breastfeeding on obesity and type 2 diabetes risk factors in Latino youth with a family history of type 2 diabetes. AB - OBJECTIVE: To determine whether breastfeeding is related to total adiposity, regional adiposity, and glucose and insulin dynamics in overweight Latino youth throughout puberty. RESEARCH DESIGN AND METHODS: The relation between breastfeeding and diabetes risk was determined in 240 overweight (BMI > or =85th percentile) Latino children (aged 8-13 years) with a positive family history of type 2 diabetes. Children were examined at baseline (Tanner pubertal stage 1) and for 2 more years as they advanced in pubertal maturation. Children were divided into the following categories: never breastfed (n = 102), breastfed 0-5.99 months (n = 61), breastfed 6-11.99 months (n = 24), and breastfed > or =12 months (n = 53). Tanner pubertal stage was determined by physical examination. Visceral and subcutaneous abdominal fat were determined by magnetic resonance imagining, and total body fat, total lean tissue mass, and percent body fat were measured by dual-energy X-ray absorptiometry. Fasting and postchallenge glucose were assessed with a 2-h oral glucose tolerance test. Insulin sensitivity (SI), acute insulin response (AIR), and disposition index ([DI] an index of beta-cell function) were measured by frequently sampled intravenous glucose tolerance test and minimal modeling. Data were analyzed using linear mixed-effects modeling. RESULTS: There were no significant effects of breastfeeding categories on adiposity (i.e., total fat mass, total lean tissue mass, percent body fat), fat distribution (visceral and subcutaneous abdominal fat), fasting glucose or 2-h glucose, or insulin dynamics (SI, AIR, and DI) at Tanner pubertal stage 1 or on changes in these variables over pubertal transitions in overweight Latino youth. CONCLUSIONS: In this population of high-risk Latino youth, there were no significant protective effects of breastfeeding on adiposity or type 2 diabetes risk factors at Tanner pubertal stage 1 or across advances in maturation. PMID- 17277040 TI - The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. AB - OBJECTIVE: We sought to compare the effects of combined calcium and vitamin D supplementation versus placebo on blood glucose and markers of inflammation in nondiabetic adults aged > or =65 years. RESEARCH DESIGN AND METHODS: A total of 314 Caucasian adults without diabetes received either 500 mg calcium citrate and 700 IU vitamin D(3) or placebos daily for 3 years in a double-blind, randomized, controlled trial designed for bone-related outcomes. In a post hoc analysis, fasting plasma glucose (FPG), insulin sensitivity (estimated by homeostasis model assessment of insulin resistance [HOMA-IR]), plasma C-reactive protein, and interleukin-6, were measured at baseline and 3 years. RESULTS: The effects of combined calcium-vitamin D supplementation on 3-year change in FPG depended on baseline FPG (P = 0.02 for interaction). Therefore, we conducted analyses separately in participants with normal fasting glucose (NFG) (FPG <5.6 mmol/l, n = 222) and impaired fasting glucose (IFG) (FPG 5.6-6.9 mmol/l, n = 92) at baseline. Among participants with IFG at baseline, those who took combined calcium-vitamin D supplements had a lower rise in FPG at 3 years compared with those on placebo (0.02 mmol/l [0.4 mg/dl] vs. 0.34 mmol/l [6.1 mg/dl], respectively, P = 0.042) and a lower increase in HOMA-IR (0.05 vs. 0.91, P = 0.031). In the NFG subgroup, there was no difference in the change in FPG or HOMA IR between the two treatment arms. There were no differences in C-reactive protein or interleukin-6 between the two treatment arms in either subgroup. CONCLUSIONS: In healthy, older adults with IFG, supplementation with calcium and vitamin D may attenuate increases in glycemia and insulin resistance that occur over time. However, our findings should be considered hypothesis generating and need to be confirmed in randomized trials specifically designed for the outcomes of interest. PMID- 17277041 TI - Prenatal exposures and glucose metabolism in adulthood: are effects mediated through birth weight and adiposity? AB - OBJECTIVE: Birth weight has been associated with the risk of type 2 diabetes in several studies. We investigated whether prenatal influences on birth weight (gestational age, parity, preeclampsia, prepregnancy BMI, smoking during pregnancy, and socioeconomic position [SEP]) were associated with glucose metabolism in midlife and the role of birth weight for gestational age (BGA) and adult adiposity in mediating these associations. RESEARCH DESIGN AND METHODS: Data from 7,518 participants of the 1958 British Birth Cohort with information on A1C at age 45 years were analyzed. Associations between prenatal exposures and A1C > or =6% were examined using a series of logistic regression models. The basic model consisted of all prenatal factors (except parity) adjusted for sex and family history of type 2 diabetes. Further adjustments included BGA only, concurrent adiposity only (BMI and waist circumference), and BGA plus adiposity. RESULTS: In the basic model, preeclampsia (odds ratio 1.78 [95% CI 1.14-2.80]), prepregnancy BMI > or =25 kg/m(2) (1.90 [1.45-2.47]), maternal smoking (1.33 [1.04-1.71]), and manual SEP (1.87 [1.36-2.58]) were independently associated with A1C at 45 years of age. Adjustment for BGA had little impact on the prenatal factors/A1C associations, whereas adjustment for adult adiposity at 45 years substantially reduced associations for prepregnancy BMI, smoking during pregnancy, and SEP. CONCLUSIONS: Prenatal exposures were related to blood glucose levels in mid-adulthood. Associations for several prenatal factors were largely mediated through adult adiposity but surprisingly not through birth weight. Prenatal exposures are likely to have the strongest effect on glucose metabolism indirectly through their influence on adiposity. PMID- 17277042 TI - Using continuous glucose monitoring to measure the frequency of low glucose values when using biphasic insulin aspart 30 compared with biphasic human insulin 30: a double-blind crossover study in individuals with type 2 diabetes. AB - OBJECTIVE: Rapid-acting insulin analogs in basal-bolus regimens can reduce nocturnal hypoglycemia, so it is conceivable that twice-daily biphasic insulin analogs might reduce hypoglycemia in patients with insulin-treated type 2 diabetes. We used a continuous glucose monitoring system (CGMS) and self-reported episodes to investigate differences in the frequency of low glucose values in patients with type 2 diabetes, using either biphasic insulin aspart 30 (BIAsp 30) or biphasic human insulin 30 (BHI 30). RESEARCH DESIGN AND METHODS: This was a double-blind, two-period, crossover trial involving 160 subjects. After 8 weeks' run-in, subjects were randomized to the first of two 16-week treatment periods. RESULTS: No differences in overall incidence of low interstitial glucose (IG) were found. Twenty-four-hour plots of CGMS showed low IG was more frequent at night than during the day and was unrecognized by patients. At night, subjects spent significantly less time (percentage of total CGMS recorded) with IG <3.5 and <2.5 mmol/l during BIAsp 30 than during BHI 30 treatment, respectively (<3.5 mmol/l: 6.36 vs. 7.93% [mean], 0.67 vs. 2.43% [median], P = 0.018; <2.5 mmol/l: 2.35 vs. 2.86% [mean], 0 vs. 0% [median], P = 0.0467). No treatment difference in A1C was observed. CONCLUSIONS: Overall rates of low glucose over 24 h were not different but were twice as frequent at night than during the day in individuals with type 2 diabetes. Compared with BHI 30, BIAsp 30 was associated with similar low IG readings over 24 h but with fewer nocturnal episodes and less self reported nocturnal hypoglycemia. PMID- 17277043 TI - Associations of MTHFR DNMT3b 4977 bp deletion in mtDNA and GSTM1 deletion, and aberrant CpG island hypermethylation of GSTM1 in non-obstructive infertility in Indian men. AB - Methylenetetrahydrofolate (MTHFR) and DNMT3b play imperative roles in DNA synthesis and de novo methylation. GSTM1 is involved in detoxification of carcinogens. Mitochondrial DNA deletion has been associated with lower motility in human sperm. We analysed if polymorphisms in MTHFR (C677T and A1298C) and DNMT3b (C46359T) are associated with non-obstructive male infertility. We also analysed if folate, vitamin B(12), homocysteine (Hcy), 8'-hydroxy-2' deoxygnanosine (8-OHdG) levels, dietary folate intake and mtDNA deletion (4977 bp) affects fertility, such interactions are modified by deletion and methylation of GSTM1. In this case-control study, we included 179 oligoasthenoteratozoospermia patients and 200 fertile men. Single-nucleotide polymorphism analysis was performed by PCR-restriction fragment length polymorphism. The MTHFR (C677T and A1298C) and DNMT3b (C46359T) frequencies did not differ significantly in two groups. GSTM1 in association with mtDNA 4977 deletion is significantly associated with infertility. Plasma folate and vitamin B(12) levels are decreased and total Hcy is elevated in infertile men. GSTM1 methylation status was investigated by methylation-specific PCR. Methylation is significantly correlated with GSTM1 reduced/loss of expression in infertile men. Infertile men have significantly higher 8-OHdG levels. Dietary folate intake is not linked with GSTM1 methylation. Low folate intake in association with CT + TT genotypes (C677T) has significant protective effect on GSTM1 methylation. Results indicate that micronutrients, 8-OHdG levels, mtDNA deletion and GSTM1 promoter methylation are frequent alterations in infertility. PMID- 17277044 TI - Long pentraxin 3 in pulmonary infection and acute lung injury. AB - Long pentraxin 3 (PTX3) is a newly discovered acute phase protein produced at the sites of infection and inflammation by tissue cells, macrophages, monocytes, and dendritic cells. PTX3 plays an important role in preventing infection of certain fungi, bacteria, and viruses in the lung. Recombinant PTX3 has been proposed as a potential antifungal molecule for therapy. However, under certain experimental conditions, such as intestinal ischemia-reperfusion, high volume mechanical ventilation, or severe bacterial infection, increased expression of PTX3 is associated with more severe lung injury. Therefore, it is necessary to further explore the sources of PTX3 in the lung and the regulatory mechanisms of its expression. It is also essential to further determine how PTX3 binds to pathogens, complement, and apoptotic cells, and to determine whether PTX3 has a specific receptor in targeted cells. These studies will provide insight into the pathological processes of pulmonary infection and acute lung injury and provide potential novel therapeutic strategies to control pulmonary infections without severe lung injury. PMID- 17277045 TI - Downregulation of migration inhibitory factor is critical for estrogen-mediated attenuation of lung tissue damage following trauma-hemorrhage. AB - Although studies have shown that 17beta-estradiol (E(2)) prevents neutrophil infiltration and organ damage following trauma-hemorrhage, the mechanism by which E(2) inhibits neutrophil transmigration remains unknown. Macrophage migration inhibitory factor (MIF) is thought to play a central role in exacerbation of inflammation and is associated with lung injury. MIF regulates the inflammatory response through modulation of Toll-like receptor 4 (TLR4). Activation of TLR4 results in the release of proinflammatory cytokines and chemokines, which induce neutrophil infiltration and subsequent tissue damage. We hypothesized that E(2) mediates its salutary effects in the lung following trauma-hemorrhage via negative regulation of MIF and modulation of TLR4 and cytokine-induced chemotaxis. C3H/HeOuJ mice were subjected to trauma-hemorrhage (mean blood pressure 35 +/- 5 mmHg for approximately 90 min, then resuscitation) or sham operation. Mice received vehicle, E(2), or E(2) in combination with recombinant mouse MIF protein (rMIF). Trauma-hemorrhage increased lung MIF and TLR4 protein levels as well as lung and systemic levels of cytokines/chemokines. Treatment of animals with E(2) following trauma-hemorrhage prevented these changes. However, administration of rMIF protein with E(2) abolished the E(2)-mediated decrease in lung TLR4 levels, lung and plasma levels of IL-6, TNF-alpha, monocyte chemoattractant protein-1, and keratinocyte-derived chemokine (KC). Administration of rMIF protein also prevented E(2)-mediated reduction in neutrophil influx and tissue damage in the lungs following trauma-hemorrhage. These results suggest that the protective effects of E(2) on lung injury following trauma-hemorrhage are mediated via downregulation of lung MIF and TLR4 induced cytokine/chemokine production. PMID- 17277046 TI - A Ba2+-resistant, acid-sensitive K+ conductance in Na+-absorbing H441 human airway epithelial cells. AB - By analysis of whole cell membrane currents in Na(+)-absorbing H441 human airway epithelial cells, we have identified a K(+) conductance (G(K)) resistant to Ba(2+) but sensitive to bupivacaine or extracellular acidification. In polarized H441 monolayers, we have demonstrated that bupivacaine, lidocaine, and quinidine inhibit basolateral membrane K(+) current (I(Bl)) whereas Ba(2+) has only a weak inhibitory effect. I(Bl) was also inhibited by basolateral acidification, and, although subsequent addition of bupivacaine caused a further fall in I(Bl), acidification had no effect after bupivacaine, demonstrating that cells grown under these conditions express at least two different bupivacaine-sensitive K(+) channels, only one of which is acid sensitive. Basolateral acidification also inhibited short-circuit current (I(SC)), and basolateral bupivacaine, lidocaine, quinidine, and Ba(2+) inhibited I(SC) at concentrations similar to those needed to inhibit I(Bl), suggesting that the K(+) channels underlying I(Bl) are part of the absorptive mechanism. Analyses using RT-PCR showed that mRNA encoding several two-pore domain K(+) (K2P) channels was detected in cells grown under standard conditions (TWIK-1, TREK-1, TASK-2, TWIK-2, KCNK-7, TASK-3, TREK-2, THIK-1, and TALK-2). We therefore suggest that K2P channels underlie G(K) in unstimulated cells and so maintain the driving force for Na(+) absorption. Since this ion transport process is vital to lung function, K2P channels thus play an important but previously undocumented role in pulmonary physiology. PMID- 17277047 TI - Regression of chronic hypoxic pulmonary hypertension by simvastatin. AB - The 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor, simvastatin, has been shown to attenuate chronic hypoxic pulmonary hypertension (CHPH). Here, we assess whether simvastatin is capable of inducing regression of established CHPH and explore potential mechanisms of statin effect. Rats (n = 8 in each group) were exposed to chronic hypoxia (10% Fi(O(2))) for 2 or 4 wk. Simvastatin treatment (20 mg.kg(-1).day(-1)) commenced after 2 wk of hypoxia, at which time CHPH was fully established, reduced mean pulmonary artery pressure (19 +/- 0.5 vs. 27 +/- 0.9 mmHg; P < 0.001), the ratio of right ventricular free wall to left ventricular plus septal weight (0.41 +/- 0.03 vs. 0.54 +/- 0.03; P < 0.001), and medial thickening of small pulmonary arteries (13 +/- 0.4 vs. 16 +/- 0.4%; P < 0.01) compared with 4-wk hypoxic controls. Supplementation with mevalonate (50 mg.kg(-1).day(-1)) prevented the attenuation of CHPH induced by simvastatin during 2 wk of hypoxia. Because statins are known to inhibit Rho-kinase (ROCK), we determined expression of ROCK-1 and -2 in whole lung by Western blot and ROCK activity by phosphorylation of the myosin-binding subunit of myosin phosphatase. Expression of both ROCK-1 and -2 were markedly diminished in simvastatin-treated animals during normoxia and hypoxia (2- and 4-wk) exposure (P < 0.01). ROCK activity was increased threefold under hypoxic conditions and normalized with simvastatin treatment (P < 0.001). We conclude that simvastatin attenuates and induces regression of established CHPH through inhibition of HMG-CoA reductase. Inhibition of ROCK expression and activity may be an important mechanism of statin effect. PMID- 17277048 TI - Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-alpha in human airway smooth muscle cells. AB - Tumor necrosis factor (TNF)-alpha is a potent inflammatory cytokine implicated in the exacerbation of asthma. Chronic exposure to TNF-alpha has been reported to induce G protein-coupled receptor desensitization, but adenylyl cyclase sensitization, in airway smooth muscle cells by an unknown mechanism. Cyclic AMP, which is synthesized by adenylyl cyclases in response to G protein-coupled receptor signals, is an important second messenger involved in the regulation of the airway muscle proliferation, migration, and tone. In other cell types, TNF alpha receptors transactivate the EGF receptor, which activates raf-1 kinase. Further studies in transfected cells show that raf-1 kinase can phosphorylate and activate some isoforms of adenylyl cyclase. Cultured human airway smooth muscle cells were treated with TNF-alpha in the presence or absence of inhibitors of prostaglandin signaling, protein kinases, or G(i) proteins. TNF-alpha caused a significant dose- (1-10 ng/ml) and time-dependent (24 and 48 h) increase in forskolin-stimulated adenylyl cyclase activity, which was abrogated by pretreatment with GW5074 (a raf-1 kinase inhibitor), was partially inhibited by an EGF receptor inhibitor, but was unaffected by pertussis toxin. TNF-alpha also increased phosphorylation of Ser(338) on raf-1 kinase, indicative of activation. IL-1beta and EGF sensitization of adenylyl cyclase activity was also sensitive to raf-1 kinase inhibition by GW5074. Taken together, these studies link two signaling pathways not previously characterized in human airway smooth muscle cells: TNF-alpha transactivation of the EGF receptor, with subsequent raf-1 kinase-mediated activation of adenylyl cyclase. PMID- 17277049 TI - Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension. AB - Idiopathic pulmonary arterial hypertension (PAH) is characterized by proliferation of pulmonary vascular endothelial and smooth muscle cells causing increased vascular resistance and right heart failure. Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) are believed to cause the familial form of the disease. Reduced expression of BMPR2 is also noted in secondary PAH. Recent advances in the therapy of PAH have improved quality of life and survival, but many patients continue to do poorly. The possibility of treating PAH via improving BMPR2 signaling is thus a rational consideration. Such an approach could be synergistic with or additive to current treatments. We developed adenoviral vectors containing the BMPR2 gene. Transfection of cells in vitro resulted in upregulation of SMAD signaling and reduced cell proliferation. Targeted delivery of vector to the pulmonary vascular endothelium of rats substantially reduced the pulmonary hypertensive response to chronic hypoxia, as reflected by reductions in pulmonary artery and right ventricular pressures, right ventricular hypertrophy, and muscularization of distal pulmonary arterioles. These data provide further evidence for a role for BMPR2 in PAH and provide a rationale for the development of therapies aimed at improving BMPR2 signaling. PMID- 17277050 TI - Characterization of the signaling domain of the NO-responsive regulator NorR from Ralstonia eutropha H16 by site-directed mutagenesis. AB - In Ralstonia eutropha H16, the nitric oxide (NO)-responsive transcriptional activator NorR controls the expression of a dicistronic operon that encodes a membrane-bound NO reductase, NorB, and a protein of unknown function, NorA. The N terminal domain (NTD) of NorR is responsible for perception of the signal molecule, nitric oxide. Thirteen out of 29 conserved residues of the NTD were exchanged by site-directed mutagenesis. Replacement of R63, R72, D93, D96, C112, D130, or F137 strongly decreased NorR-dependent promoter activation, while the exchange of Y95 or H110 led to an increase in promoter activity compared to that of the wild type. A purified truncated NorR comprising only the NTD (NorR-NTD) contained one iron atom per molecule and was able to bind NO in the as-isolated state. Based on the iron content of NorR-NTD proteins with single amino acid replacements, residues R72, D93, D96, C112, and D130 are likely candidates for iron ligands. Residues R63, Y95, and H110 appear not to be involved in NO binding but may take part in subsequent steps of the signal transduction mechanism of NorR. PMID- 17277051 TI - sigmaB regulates IS256-mediated Staphylococcus aureus biofilm phenotypic variation. AB - Biofilm formation in Staphylococcus aureus is subject to phase variation, and biofilm-negative derivatives emerge sporadically from a biofilm-positive bacterial population. To date, the only known mechanism for generating biofilm phenotypic variation in staphylococci is the reversible insertion/excision of IS256 in biofilm-essential genes. In this study, we present evidence suggesting that the absence of the sigma(B) transcription factor dramatically increases the rate of switching to the biofilm-negative phenotype in the clinical isolate S. aureus 15981, under both steady-state and flow conditions. The phenotypic switching correlates with a dramatic increase in the number of IS256 copies in the chromosomes of biofilm-negative variants, as well as with an augmented IS256 insertion frequency into the icaC and the sarA genes. IS256-mediated biofilm switching is reversible, and biofilm-positive variants could emerge from biofilm negative sigma(B) mutants. Analysis of the chromosomal insertion frequency using a recombinant IS256 element tagged with an erythromycin marker showed an almost three-times-higher transposition frequency in a Deltasigma(B) strain. However, regulation of IS256 activity by sigma(B) appears to be indirect, since transposase transcription is not affected in the absence of sigma(B) and IS256 activity is inhibited to wild-type levels in a Deltasigma(B) strain under NaCl stress. Overall, our results identify a new role for sigma(B) as a negative regulator of insertion sequence transposition and support the idea that deregulation of IS256 activity abrogates biofilm formation capacity in S. aureus. PMID- 17277054 TI - IntDOT interactions with core- and arm-type sites of the conjugative transposon CTnDOT. AB - CTnDOT is a Bacteroides conjugative transposon (CTn) that has facilitated the spread of antibiotic resistances among bacteria in the human gut in recent years. Although the integrase encoded by CTnDOT (IntDOT) carries the C-terminal set of conserved amino acids that is characteristic of the tyrosine family of recombinases, the reaction it catalyzes involves a novel step that creates a short region of heterology at the joined ends of the element during recombination. Also, in contrast to tyrosine recombinases, IntDOT catalyzes a reaction that is not site specific. To determine what types of contacts IntDOT makes with the DNA during excision and integration, we first developed an agarose gel-based assay for CTnDOT recombination, which facilitated the purification of the native IntDOT protein. The partially purified IntDOT was then used for DNase I footprinting analysis of the integration site attDOT and the excision sites attL and attR. Our results indicate that CTnDOT has five or six arm sites that are likely to be involved in forming higher-order nucleoprotein complexes necessary for synapsis. In addition, there are four core sites that flank the sites of strand exchange during recombination. Thus, despite the fact that the reaction catalyzed by IntDOT appears to be different from that typically catalyzed by tyrosine recombinases, the protein-DNA interactions required for higher-order structures and recombination appear to be similar. PMID- 17277053 TI - His(20) provides the sole functionally significant side chain in the essential TonB transmembrane domain. AB - The cytoplasmic membrane protein TonB couples the protonmotive force of the cytoplasmic membrane to active transport across the outer membrane of Escherichia coli. The uncleaved amino-terminal signal anchor transmembrane domain (TMD; residues 12 to 32) of TonB and the integral cytoplasmic membrane proteins ExbB and ExbD are essential to this process, with important interactions occurring among the several TMDs of all three proteins. Here, we show that, of all the residues in the TonB TMD, only His(20) is essential for TonB activity. When alanyl residues replaced all TMD residues except Ser(16) and His(20), the resultant "all-Ala Ser(16) His(20)" TMD TonB retained 90% of wild-type iron transport activity. Ser(16)Ala in the context of a wild-type TonB TMD was fully active. In contrast, His(20)Ala in the wild-type TMD was entirely inactive. In more mechanistically informative assays, the all-Ala Ser(16) His(20) TMD TonB unexpectedly failed to support formation of disulfide-linked dimers by TonB derivatives bearing Cys substitutions for the aromatic residues in the carboxy terminus. We hypothesize that, because ExbB/D apparently cannot efficiently down regulate conformational changes at the TonB carboxy terminus through the all-Ala Ser(16) His(20) TMD, the TonB carboxy terminus might fold so rapidly that disulfide-linked dimers cannot be efficiently trapped. In formaldehyde cross linking experiments, the all-Ala Ser(16) His(20) TMD also supported large numbers of apparently nonspecific contacts with unknown proteins. The all-Ala Ser(16) His(20) TMD TonB retained its dependence on ExbB/D. Together, these results suggest that a role for ExbB/D might be to control rapid and nonspecific folding that the unregulated TonB carboxy terminus otherwise undergoes. Such a model helps to reconcile the crystal/nuclear magnetic resonance structures of the TonB carboxy terminus with conformational changes and mutant phenotypes observed at the TonB carboxy terminus in vivo. PMID- 17277052 TI - Streptococcus gordonii Hsa environmentally constrains competitive binding by Streptococcus sanguinis to saliva-coated hydroxyapatite. AB - Competition between pioneer colonizing bacteria may determine polymicrobial succession during dental plaque development, but the ecological constraints are poorly understood. For example, more Streptococcus sanguinis than Streptococcus gordonii organisms are consistently isolated from the same intraoral sites, yet S. gordonii fails to be excluded and survives as a species over time. To explain this observation, we hypothesized that S. gordonii could compete with S. sanguinis to adhere to saliva-coated hydroxyapatite (sHA), an in vitro model of the tooth surface. Both species bound similarly to sHA, yet 10- to 50-fold excess S. gordonii DL1 reduced binding of S. sanguinis SK36 by 85 to >95%. S. sanguinis, by contrast, did not significantly compete with S. gordonii to adhere. S. gordonii competed with S. sanguinis more effectively than other species of oral streptococci and depended upon the salivary film on HA. Next, putative S. gordonii adhesins were analyzed for contributions to interspecies competitive binding. Like wild-type S. gordonii, isogenic mutants with mutations in antigen I/II polypeptides (sspAB), amylase-binding proteins (abpAB), and Csh adhesins (cshAB) competed effectively against S. sanguinis. By contrast, an hsa-deficient mutant of S. gordonii showed significantly reduced binding and competitive capabilities, while these properties were restored in an hsa-complemented strain. Thus, Hsa confers a selective advantage to S. gordonii over S. sanguinis in competitive binding to sHA. Hsa expression may, therefore, serve as an environmental constraint against S. sanguinis, enabling S. gordonii to persist within the oral cavity, despite the greater natural prevalence of S. sanguinis in plaque and saliva. PMID- 17277055 TI - In vivo demonstration of FNR dimers in response to lower O(2) availability. AB - Escherichia coli FNR is an O(2)-sensing transcription factor. In vitro studies indicate that anaerobic iron-sulfur cluster acquisition promotes FNR dimerization. Here, two-hybrid assays show that iron-sulfur cluster-dependent FNR dimers are formed in vivo in response to lower O(2) availability, consistent with the current model of FNR activation. PMID- 17277056 TI - Expression of the bviIR and cepIR quorum-sensing systems of Burkholderia vietnamiensis. AB - Burkholderia vietnamiensis has both the cepIR quorum-sensing system that is widely distributed among the Burkholderia cepacia complex (BCC) and the bviIR system. Comparison of the expression of cepI, cepR, bviI, and bviR-luxCDABE fusions in B. vietnamiensis G4 and the G4 cepR and bviR mutants determined that the expression of bviI requires both a functional cognate regulator, BviR, and functional CepR. The cepIR system, however, is not regulated by BviR. Unlike the cepIR genes in other BCC species, the cepIR genes are not autoregulated in G4. N Acyl-homoserine lactone (AHL) production profiles in G4 cepI, cepR, bviI, and bviR mutants confirmed the regulatory organization of the G4 quorum-sensing systems. The regulatory network in strain PC259 is similar to that in G4, except that CepR positively regulates cepI and negatively regulates cepR. AHL production and the bviI expression levels in seven B. vietnamiensis isolates were compared. All strains produced N-octanoyl-homoserine lactone and N-hexanoyl-homoserine lactone; however, only one of four clinical strains but all three environmental strains produced the BviI synthase product, N-decanoyl-homoserine lactone (DHL). The three strains that did not produce DHL expressed bviR but not bviI. Heterologous expression of bviR restored DHL production in these strains. The bviIR loci of the non-DHL-producing strains were sequenced to confirm that bviR encodes a functional transcriptional regulator. Lack of expression of G4 bviI in these three strains indicated that an additional regulatory element may be involved in the regulation of bviIR expression in certain strains of B. vietnamiensis. PMID- 17277057 TI - Role of the PDZ domains in Escherichia coli DegP protein. AB - PDZ domains are modular protein interaction domains that are present in metazoans and bacteria. These domains possess unique structural features that allow them to interact with the C-terminal residues of their ligands. The Escherichia coli essential periplasmic protein DegP contains two PDZ domains attached to the C terminal end of the protease domain. In this study we examined the role of each PDZ domain in the protease and chaperone activities of this protein. Specifically, DegP mutants with either one or both PDZ domains deleted were generated and tested to determine their protease and chaperone activities, as well as their abilities to sequester unfolded substrates. We found that the PDZ domains in DegP have different roles; the PDZ1 domain is essential for protease activity and is responsible for recognizing and sequestering unfolded substrates through C-terminal tags, whereas the PDZ2 domain is mostly involved in maintaining the hexameric cage of DegP. Interestingly, neither of the PDZ domains was required for the chaperone activity of DegP. In addition, we found that the loops connecting the protease domain to PDZ1 and connecting PDZ1 to PDZ2 are also essential for the protease activity of the hexameric DegP protein. New insights into the roles of the PDZ domains in the structure and function of DegP are provided. These results imply that DegP recognizes substrate molecules targeted for degradation and substrate molecules targeted for refolding in different manners and suggest that the substrate recognition mechanisms may play a role in the protease-chaperone switch, dictating whether the substrate is degraded or refolded. PMID- 17277058 TI - Performance of the translational apparatus varies with the ecological strategies of bacteria. AB - Protein synthesis is the predominant activity of growing bacteria; the protein synthesis system accounts for more than one-half the cell's dry mass and consumes most of the cell's energy during rapid growth. Translation has been studied extensively using model organisms, and the translational apparatus is qualitatively similar in terms of structure and function across all known forms of life. However, little is known about variation between organisms in translational performance. Using measurements of macromolecular content in a phylogenetically diverse collection of bacteria with contrasting ecological strategies, we found that the translational power (the rate of protein synthesis normalized to the mass of the protein synthesis system) is three- to fourfold higher among bacteria that respond rapidly to nutrient availability than among bacteria that respond slowly. An analysis of codon use in completely sequenced bacterial genomes confirmed that the selective forces acting on translation vary with the ecological strategy. We propose that differences in translational power result from ecologically based variation among microbes in the relative importance of two competing benefits: reducing the biomass invested in the protein synthesis system and reducing the energetic expense of protein synthesis. PMID- 17277059 TI - The transcriptional regulators NorG and MgrA modulate resistance to both quinolones and beta-lactams in Staphylococcus aureus. AB - MgrA is a known regulator of the expression of several multidrug transporters in Staphylococcus aureus. We identified another regulator of multiple efflux pumps, NorG, by its ability, like that of MgrA, to bind specifically to the promoter of the gene encoding the NorA efflux pump. NorG is a member of the family of the GntR-like transcriptional regulators, and it binds specifically to the putative promoters of the genes encoding multidrug efflux pumps NorA, NorB, NorC, and AbcA. Overexpression of norG produces a threefold increase in norB transcripts associated with a fourfold increase in the level of resistance to quinolones. In contrast, disruption of norG produces no change in the level of transcripts of norA, norB, and norC but causes an increase of at least threefold in the transcript level of abcA, associated with a fourfold increase in resistance to methicillin, cefotaxime, penicillin G, and nafcillin. Overexpression of cloned abcA caused an 8- to 128-fold increase in the level of resistance to all four beta-lactam antibiotics. Furthermore, MgrA and NorG have opposite effects on norB and abcA expression. MgrA acts as an indirect repressor for norB and a direct activator for abcA, whereas NorG acts as a direct activator for norB and a direct repressor for abcA. PMID- 17277060 TI - Characterization of a pseudomonad 2-nitrobenzoate nitroreductase and its catabolic pathway-associated 2-hydroxylaminobenzoate mutase and a chemoreceptor involved in 2-nitrobenzoate chemotaxis. AB - Pseudomonas fluorescens strain KU-7 is a prototype microorganism that metabolizes 2-nitrobenzoate (2-NBA) via the formation of 3-hydroxyanthranilate (3-HAA), a known antioxidant and reductant. The initial two steps leading to the sequential formation of 2-hydroxy/aminobenzoate and 3-HAA are catalyzed by a NADPH-dependent 2-NBA nitroreductase (NbaA) and 2-hydroxylaminobenzoate mutase (NbaB), respectively. The 216-amino-acid protein NbaA is 78% identical to a plasmid encoded hypothetical conserved protein of Polaromonas strain JS666; structurally, it belongs to the homodimeric NADH:flavin mononucleotide (FMN) oxidoreductase like fold family. Structural modeling of complexes with the flavin, coenzyme, and substrate suggested specific residues contributing to the NbaA catalytic activity, assuming a ping-pong reaction mechanism. Mutational analysis supports the roles of Asn40, Asp76, and Glu113, which are predicted to form the binding site for a divalent metal ion implicated in FMN binding, and a role in NADPH binding for the 10-residue insertion in the beta5-alpha2 loop. The 181-amino-acid sequence of NbaB is 35% identical to the 4-hydroxylaminobenzoate lyases (PnbBs) of various 4-nitrobenzoate-assimilating bacteria, e.g., Pseudomonas putida strain TW3. Coexpression of nbaB with nbaA in Escherichia coli produced a small amount of 3-HAA from 2-NBA, supporting the functionality of the nbaB gene. We also showed by gene knockout and chemotaxis assays that nbaY, a chemoreceptor NahY homolog located downstream of the nbaA gene, is responsible for strain KU-7 being attracted to 2-NBA. NbaY is the first chemoreceptor in nitroaromatic metabolism to be identified, and this study completes the gene elucidation of 2-NBA metabolism that is localized within a 24-kb chromosomal locus of strain KU-7. PMID- 17277062 TI - Intermolecular forces and enthalpies in the adhesion of Streptococcus mutans and an antigen I/II-deficient mutant to laminin films. AB - The antigen I/II family of surface proteins is expressed by most oral streptococci, including Streptococcus mutans, and mediates specific adhesion to, among other things, salivary films and extracellular matrix proteins. In this study we showed that antigen I/II-deficient S. mutans isogenic mutant IB03987 was nearly unable to adhere to laminin films under flow conditions due to a lack of specific interactions (0.8 x 10(6) and 1.1 x 10(6) cells cm(-2) at pH 5.8 and 6.8, respectively) compared with parent strain LT11 (21.8 x 10(6) and 26.1 x 10(6) cells cm(-2)). The adhesion of both the parent and mutant strains was slightly greater at pH 6.8 than at pH 5.8. In addition, atomic force microscopy (AFM) experiments demonstrated that the parent strain experienced less repulsion when it approached a laminin film than the mutant experienced. Upon retraction, combined specific and nonspecific adhesion forces were stronger for the parent strain (up to -5.0 and -4.9 nN at pH 5.8 and 6.8, respectively) than for the mutant (up to -1.5 and -2.1 nN), which was able to interact only through nonspecific interactions. Enthalpy was released upon adsorption of laminin to the surface of the parent strain but not upon adsorption of laminin to the surface of IB03987. A comparison of the adhesion forces in AFM with the adhesion forces reported for specific ligand-receptor complexes resulted in the conclusion that the number of antigen I/II binding sites for laminin on S. mutans LT11 is on the order of 6 x 10(4) sites per organism and that the sites are probably arranged along exterior surface structures, as visualized here by immunoelectron microscopy. PMID- 17277061 TI - Genome of the opportunistic pathogen Streptococcus sanguinis. AB - The genome of Streptococcus sanguinis is a circular DNA molecule consisting of 2,388,435 bp and is 177 to 590 kb larger than the other 21 streptococcal genomes that have been sequenced. The G+C content of the S. sanguinis genome is 43.4%, which is considerably higher than the G+C contents of other streptococci. The genome encodes 2,274 predicted proteins, 61 tRNAs, and four rRNA operons. A 70-kb region encoding pathways for vitamin B(12) biosynthesis and degradation of ethanolamine and propanediol was apparently acquired by horizontal gene transfer. The gene complement suggests new hypotheses for the pathogenesis and virulence of S. sanguinis and differs from the gene complements of other pathogenic and nonpathogenic streptococci. In particular, S. sanguinis possesses a remarkable abundance of putative surface proteins, which may permit it to be a primary colonizer of the oral cavity and agent of streptococcal endocarditis and infection in neutropenic patients. PMID- 17277063 TI - Characterization of the proteasome accessory factor (paf) operon in Mycobacterium tuberculosis. AB - In a previous screen for Mycobacterium tuberculosis mutants that are hypersusceptible to reactive nitrogen intermediates (RNI), two genes associated with the M. tuberculosis proteasome were identified. One of these genes, pafA (proteasome accessory factor A), encodes a protein of unknown function. In this work, we determined that pafA is in an operon with two additional genes, pafB and pafC. In order to assess the contribution of these genes to RNI resistance, we isolated mutants with transposon insertions in pafB and pafC. In contrast to the pafA mutant, the pafB and pafC mutants were not severely sensitized to RNI, but pafB and pafC were nonetheless required for full RNI resistance. We also found that PafB and PafC interact with each other and that each is likely required for the stability of the other protein in M. tuberculosis. Finally, we show that the presence of PafA, but not PafB or PafC, regulates the steady-state levels of three proteasome substrates. Taken together, these data demonstrate that PafA, but not PafB or PafC, is critical for maintaining the steady-state levels of known proteasome substrates, whereas all three proteins appear to play a role in RNI resistance. PMID- 17277064 TI - Species-specific functioning of the Pseudomonas XcpQ secretin: role for the C terminal homology domain and lipopolysaccharide. AB - Secretins are oligomeric proteins that mediate the export of macromolecules across the bacterial outer membrane. The members of the secretin superfamily possess a C-terminal homology domain that is important for oligomerization and channel formation, while their N-terminal halves are thought to be involved in system-specific interactions. The XcpQ secretin of Pseudomonas spp. is a component of the type II secretion pathway. XcpQ from Pseudomonas alcaligenes is not able to functionally replace the secretin of the closely related species Pseudomonas aeruginosa. By analysis of chimeric XcpQ proteins, a region important for species-specific functioning was mapped between amino acid residues 344 and 478 in the C-terminal homology domain. Two chromosomal suppressor mutations were obtained that resulted in the proper functioning in P. aeruginosa of P. alcaligenes XcpQ and inactive hybrids. These mutations caused a defect in the synthesis of the lipopolysaccharide (LPS) outer core region. Subsequent analysis of different LPS mutants showed that changes in the outer core and not the loss of O antigen caused the suppressor phenotype. High concentrations of divalent cations in the growth medium also allowed P. alcaligenes XcpQ and inactive hybrids to function properly in P. aeruginosa. Since divalent cations are known to affect the structure of LPS, this observation supports the hypothesis that LPS has a role in the functioning of secretins. PMID- 17277065 TI - pilQ Missense mutations have diverse effects on PilQ multimer formation, piliation, and pilus function in Neisseria gonorrhoeae. AB - Type IV pili are required for virulence in Neisseria gonorrhoeae, as they are involved in adherence to host epithelium, twitching motility, and DNA transformation. The outer membrane secretin PilQ forms a homododecameric ring through which the pilus is proposed to be secreted. pilQ null mutants are nonpiliated, and thus, all pilus-dependent functions are eliminated. Mutagenesis was performed on the middle one-third of pilQ, and mutants with colony morphologies consistent with the colony morphology of nonpiliated or underpiliated bacteria were selected. Nineteen mutants, each with a single amino acid substitution, were isolated and displayed diverse phenotypes in terms of PilQ multimer stability, pilus expression, transformation efficiency, and host cell adherence. The 19 mutants were grouped into five phenotypic classes based on functionality. Four of the five mutant classes fit the current model of pilus functionality, which proposes that a functional pilus assembly apparatus, not necessarily full-length pili, is required for transformation, while high levels of displayed pili are required for adherence. One class, despite having an underpiliated colony morphology, expressed high levels of pili yet adhered poorly, demonstrating that pilus expression is necessary but not sufficient for adherence and indicating that PilQ may be directly involved in host cell adherence. The collection of phenotypes expressed by these mutants suggests that PilQ has an active role in pilus expression and function. PMID- 17277067 TI - A phosphoenolpyruvate-dependent phosphotransferase system is the principal maltose transporter in Streptococcus mutans. AB - We report that a phosphoenolpyruvate-dependent phosphotransferase system, MalT, is the principal maltose transporter for Streptococcus mutans. MalT also contributes to maltotriose uptake. Since maltose and maltodextrins are products of starch degradation found in saliva, the ability to take up and ferment these carbohydrates may contribute to dental caries. PMID- 17277066 TI - Region-specific insertion of transposons in combination with selection for high plasmid transferability and stability accounts for the structural similarity of IncP-1 plasmids. AB - The overall architecture of IncP-1 plasmids is very conserved in that the accessory genes are typically located in one or two specific regions: between oriV and trfA and between the tra and trb operons. Various hypotheses have been formulated to explain this, but none have been tested experimentally. We investigated whether this structural similarity is due to region-specific transposition alone or also is reliant on selection for plasmids with insertions limited to these two regions. We first examined the transposition of Tn21Km into IncP-1beta plasmid pBP136 and found that most Tn21Km insertions (67%) were located around oriV. A similar experiment using the oriV region of IncP-1beta plasmid pUO1 confirmed these results. We then tested the transferability, stability, and fitness cost of different pBP136 derivatives to determine if impairment of these key plasmid characters explained the conserved plasmid architecture. Most of the pBP136 derivatives with insertions in transfer genes were no longer transferable. The plasmids with insertions in the oriV-trfA and tra-trb regions were more stable than other plasmid variants, and one of these also showed a significantly lower fitness cost. In addition, our detailed sequence analysis of IncP-1 plasmids showed that Tn402/5053-like transposons are situated predominantly between the tra and trb operons and close to the putative resolution site for the ParA resolvase, a potential hot spot for those transposons. Our study presents the first empirical evidence that region-specific insertion of transposons in combination with selection for transferable and stable plasmids explains the structural similarity of IncP-1 plasmids. PMID- 17277068 TI - Microarray analysis of transposon insertion mutations in Bacillus anthracis: global identification of genes required for sporulation and germination. AB - A transposon site hybridization (TraSH) assay was developed for functional analysis of the Bacillus anthracis genome using a mini-Tn10 transposon which permitted analysis of 82% of this pathogen's genes. The system, used to identify genes required for generation of infectious anthrax spores, spore germination, and optimal growth on rich medium, was predictive of the contributions of two conserved hypothetical genes for the phenotypes examined. PMID- 17277069 TI - Localized tufts of fibrils on Staphylococcus epidermidis NCTC 11047 are comprised of the accumulation-associated protein. AB - Staphylococcus epidermidis is both a human skin commensal and an opportunistic pathogen, causing infections linked to implanted medical devices. This paper describes localized tufts of fibrillar appendages on a subpopulation (25%) of wild-type (WT) S. epidermidis NCTC 11047 cells. The fibrils (122.2 +/- 10.8 nm long) are usually in a lateral position on the cells. Fibrillar (Fib(+)) and nonfibrillar (Fib(-)) subpopulations were separated (enriched) by 34 sequential partitions of WT cells between a buffer phase and a hexadecane phase. Following enrichment, hydrophobic cells from the hexadecane phase comprised 70% Fib(+) cells and the less hydrophobic cells from the buffer phase entirely comprised Fib(-) cells. The Fib(+) and Fib(-) subpopulations did not revert on subculture (34 times) on solid medium. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cell surface proteins from WT, Fib(+), and Fib(-) cells revealed two high-molecular-mass proteins (280 kDa and 230 kDa) on the WT and Fib(+) cells that were absent from the Fib(-) cells. Amino acid sequencing revealed that fragments of both the 280- and 230-kDa proteins had 100% identity to the accumulation-associated protein (Aap). Aap is known to cause biofilm formation if it is truncated by loss of the terminal A domain. Immunogold staining with anti-Aap antibodies labeled tuft fibrils of the WT and Fib(+) cells but not the cell surface of Fib(-) cells. The tufts were labeled with N terminally directed antibodies (anti-A domain), showing that the fibrillar Aap was not truncated on the cell surface. Thus, the presence of full-length Aap correlated with the low biofilm-forming abilities of both WT and Fib(+) S. epidermidis NCTC 11047 populations. Reverse transcription-PCR showed that aap was transcribed in both Fib(+) and Fib(-) cells. We therefore propose that full length Aap is expressed on cells of S. epidermidis NCTC 11047 as tufts of short fibrils and that fibril expression is regulated at a posttranscriptional level. PMID- 17277070 TI - Sortase-catalyzed assembly of distinct heteromeric fimbriae in Actinomyces naeslundii. AB - Two types of adhesive fimbriae are expressed by Actinomyces; however, the architecture and the mechanism of assembly of these structures remain poorly understood. In this study we characterized two fimbrial gene clusters present in the genome of Actinomyces naeslundii strain MG-1. By using immunoelectron microscopy and biochemical analysis, we showed that the fimQ-fimP-srtC1-fimR gene cluster encodes a fimbrial structure (designated type 1) that contains a major subunit, FimP, forming the shaft and a minor subunit, FimQ, located primarily at the tip. Similarly, the fimB-fimA-srtC2 gene cluster encodes a distinct fimbrial structure (designated type 2) composed of a shaft protein, FimA, and a tip protein, FimB. By using allelic exchange, we constructed an in-frame deletion mutant that lacks the SrtC2 sortase. This mutant produces abundant type 1 fimbriae and expresses the monomeric FimA and FimB proteins, but it does not assemble type 2 fimbriae. Thus, SrtC2 is a fimbria-specific sortase that is essential for assembly of the type 2 fimbriae. Together, our experiments pave the way for several lines of molecular investigation that are necessary to elucidate the fimbrial assembly pathways in Actinomyces and their function in the pathogenesis of different biofilm-related oral diseases. PMID- 17277071 TI - Initial steps of colicin E1 import across the outer membrane of Escherichia coli. AB - Data suggest a two-receptor model for colicin E1 (ColE1) translocation across the outer membrane of Escherichia coli. ColE1 initially binds to the vitamin B(12) receptor BtuB and then translocates through the TolC channel-tunnel, presumably in a mostly unfolded state. Here, we studied the early events in the import of ColE1. Using in vivo approaches, we show that ColE1 is cleaved when added to whole cells. This cleavage requires the presence of the receptor BtuB and the protease OmpT, but not that of TolC. Strains expressing OmpT cleaved ColE1 at K84 and K95 in the N-terminal translocation domain, leading to the removal of the TolQA box, which is essential for ColE1's cytotoxicity. Supported by additional in vivo data, this suggests that a function of OmpT is to degrade colicin at the cell surface and thus protect sensitive E. coli cells from infection by E colicins. A genetic strategy for isolating tolC mutations that confer resistance to ColE1, without affecting other TolC functions, is also described. We provide further in vivo evidence of the multistep interaction between TolC and ColE1 by using cross-linking followed by copurification via histidine-tagged TolC. First, secondary binding of ColE1 to TolC is dependent on primary binding to BtuB. Second, alterations to a residue in the TolC channel interfere with the translocation of ColE1 across the TolC pore rather than with the binding of ColE1 to TolC. In contrast, a substitution at a residue exposed on the cell surface abolishes both binding and translocation of ColE1. PMID- 17277072 TI - Essentiality of ribosomal and transcription antitermination proteins analyzed by systematic gene replacement in Escherichia coli. AB - We describe here details of the method we used to identify and distinguish essential from nonessential genes on the bacterial Escherichia coli chromosome. Three key features characterize our method: high-efficiency recombination, precise replacement of just the open reading frame of a chromosomal gene, and the presence of naturally occurring duplications within the bacterial genome. We targeted genes encoding functions critical for processes of transcription and translation. Proteins from three complexes were evaluated to determine if they were essential to the cell by deleting their individual genes. The transcription elongation Nus proteins and termination factor Rho, which are involved in rRNA antitermination, the ribosomal proteins of the small 30S ribosome subunit, and minor ribosome-associated proteins were analyzed. It was concluded that four of the five bacterial transcription antitermination proteins are essential, while all four of the minor ribosome-associated proteins examined (RMF, SRA, YfiA, and YhbH), unlike most ribosomal proteins, are dispensable. Interestingly, although most 30S ribosomal proteins were essential, the knockouts of six ribosomal protein genes, rpsF (S6), rpsI (S9), rpsM (S13), rpsO (S15), rpsQ (S17), and rpsT (S20), were viable. PMID- 17277073 TI - Translocation of alpha-synuclein expressed in Escherichia coli. AB - alpha-Synuclein is a major component of Lewy bodies in Parkinson's disease. Although no signal sequence is apparent, alpha-synuclein expressed in Escherichia coli is mostly located in the periplasm. The possibilities that alpha-synuclein translocated into the periplasm across the inner membrane by the SecA or the Tat targeting route identified in bacteria and that alpha-synuclein was released through MscL were excluded. The signal recognition particle-dependent pathway is involved in the translocation of alpha-synuclein. The C-terminal 99-to-140 portion of the alpha-synuclein molecule plays a signal-like role for its translocation into the periplasm, cooperating with the central 61-to-95 section. The N-terminal 1-to-60 region is not required for this translocation. PMID- 17277074 TI - Coordinated high-light response of genes encoding subunits of photosystem I is achieved by AT-rich upstream sequences in the cyanobacterium Synechocystis sp. strain PCC 6803. AB - Genes encoding subunits of photosystem I (PSI genes) in the cyanobacterium Synechocystis sp. strain PCC 6803 are actively transcribed under low-light conditions, whereas their transcription is coordinately and rapidly down regulated upon the shift to high-light conditions. In order to identify the molecular mechanism of the coordinated high-light response, we searched for common light-responsive elements in the promoter region of PSI genes. First, the precise architecture of the psaD promoter was determined and compared with the previously identified structure of the psaAB promoter. One of two promoters of the psaAB genes (P1) and of the psaD gene (P2) possessed an AT-rich light responsive element located just upstream of the basal promoter region. These sequences enhanced the basal promoter activity under low-light conditions, and their activity was transiently suppressed upon the shift to high-light conditions. Subsequent analysis of psaC, psaE, psaK1, and psaLI promoters revealed that their light response was also achieved by AT-rich sequences located at the -70 to -46 region. These results clearly show that AT-rich upstream elements are responsible for the coordinated high-light response of PSI genes dispersed throughout Synechocystis genome. PMID- 17277075 TI - Thiopurines, DNA damage, DNA repair and therapy-related cancer. AB - AIMS: The thiopurines, azathioprine, 6-mercaptopurine and 6-thioguanine are one of the success stories of chemotherapy. They are effective immunosuppressants and anti-cancer agents and are prescribed increasingly to treat inflammatory diseases. Although their metabolism has been studied in detail, the optimal use of thiopurines has been guided predominantly by clinical experience and the precise molecular events that underlie their therapeutic activity have remained unclear. The aim of this article is to review some of the properties of the thiopurines and relate them to possible therapeutic mechanisms. In particular, I consider the contribution that DNA substitution by 6-thioguanine makes to their effects as well as some of the possible harmful reactions that DNA 6-thioguanine might undergo. CONCLUSIONS: The increased chemical reactivity of DNA 6 thioguanine underlies its cytotoxic effects and is an important contributor to the anti-leukaemic effects of the thiopurines. The same enhanced reactivity may contribute to the increased risk of acute myeloid leukaemia and skin cancer in thiopurine-treated organ transplant patients. PMID- 17277076 TI - Direct measurement of force generation by actin filament polymerization using an optical trap. AB - Actin filament polymerization generates force for protrusion of the leading edge in motile cells. In protrusive structures, multiple actin filaments are arranged in cross-linked webs (as in lamellipodia or pseudopodia) or parallel bundles (as in filopodia). We have used an optical trap to directly measure the forces generated by elongation of a few parallel-growing actin filaments brought into apposition with a rigid barrier, mimicking the geometry of filopodial protrusion. We find that the growth of approximately eight actin parallel-growing filaments can be stalled by relatively small applied load forces on the order of 1 pN, consistent with the theoretical load required to stall the elongation of a single filament under our conditions. Indeed, large length fluctuations during the stall phase indicate that only the longest actin filament in the bundle is in contact with the barrier at any given time. These results suggest that force generation by small actin bundles is limited by a dynamic instability of single actin filaments, and therefore living cells must use actin-associated factors to suppress this instability to generate substantial forces by elongation of parallel bundles of actin filaments. PMID- 17277078 TI - Open-cap conformation of intramembrane protease GlpG. AB - The active sites of intramembrane proteases are positioned in the lipid bilayer to facilitate peptide bond hydrolysis in the membrane. Previous crystallographic analysis of Escherichia coli GlpG, an intramembrane protease of the rhomboid family, has revealed an internal and hydrophilic active site in an apparently closed conformation. Here we describe the crystal structure of GlpG in a more open conformation, where the capping loop L5 has been lifted, exposing the previously buried and catalytically essential Ser-201 to outside aqueous solution. A water molecule now moves into the putative oxyanion hole that is constituted of a main-chain amide (Ser-201) and two conserved side chains (His 150 and Asn-154). The loop movement also destabilizes a hydrophobic side chain (Phe-245) previously buried between transmembrane helices S2 and S5 and creates a side portal from the lipid to protease active site. These results provide insights into the conformational plasticity of GlpG to accommodate substrate binding and catalysis and into the chirality of the reaction intermediate. PMID- 17277077 TI - Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis. AB - There is emerging evidence for the existence of secretory pathways for superoxide dismutase (SOD1) mutants linked to amyotrophic lateral sclerosis (ALS) and for neurotoxicity of extracellular mutant SOD1. This evidence led us to test immunization protocols aiming to reduce the burden of extracellular SOD1 mutants in nervous tissue of mice models of ALS, by using bacterially purified recombinant SOD1 mutant protein as an immunogen. First, a vaccination was tested on a G37R SOD1 mouse strain with late-onset disease exhibiting levels of mutant SOD1 protein at 4-fold higher than normal SOD1 levels. Repeated injections of adjuvant/SOD1 mutant with a final booster injection before symptoms at 6 months of age were effective in delaying disease onset and extending the life span of G37R SOD1 mice by >4 weeks. Western blot analysis with a monoclonal antibody specific to mutant SOD1 forms provided evidence of clearance of SOD1 species in the spinal cord of vaccinated G37R SOD1 mice. In contrast, this vaccination approach failed to confer significant protection in G93A SOD1 mice with extreme overexpression of mutant SOD1. Nonetheless, a passive immunization through intraventricular infusion of purified anti-human SOD1 antibody with osmotic minipump succeeded in alleviating disease symptoms and prolonging the life span of G93A SOD1 mice. From these results, we propose that immunization strategies should be considered as potential avenues for treatment of familial ALS caused by SOD1 mutations. PMID- 17277079 TI - Light-powering Escherichia coli with proteorhodopsin. AB - Proteorhodopsin (PR) is a light-powered proton pump identified by community sequencing of ocean samples. Previous studies have established the ecological distribution and enzymatic activity of PR, but its role in powering cells and participation in ocean energy fluxes remains unclear. Here, we show that when cellular respiration is inhibited by depleting oxygen or by the respiratory poison azide, Escherichia coli cells expressing PR become light-powered. Illumination of these cells with light coinciding with PR's absorption spectrum creates a proton motive force (pmf) that turns the flagellar motor, yielding cells that swim when illuminated with green light. By measuring the pmf of individual illuminated cells, we quantify the coupling between light-driven and respiratory proton currents, estimate the Michaelis-Menten constant (Km) of PR (10(3) photons per second/nm2), and show that light-driven pumping by PR can fully replace respiration as a cellular energy source in some environmental conditions. Moreover, sunlight-illuminated PR+ cells are less sensitive to azide than PR- cells, consistent with PR+ cells possessing an alternative means of maintaining cellular pmf and, thus, viability. Proteorhodopsin allows Escherichia coli cells to withstand environmental respiration challenges by harvesting light energy. PMID- 17277081 TI - Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. AB - Mast cells are immune sentinels that participate in the defense against bacteria and parasites. Resident within the joint, mast cells become activated in human rheumatoid arthritis and are implicated in the pathogenesis of experimental murine synovitis. However, their arthritogenic role remains undefined. Using a model of autoantibody-induced arthritis, we show that mast cells contribute to the initiation of inflammation within the joint by elaboration of IL-1. Mast cells become activated to produce this cytokine via the IgG immune complex receptor FcgammaRIII. Interestingly, mast cells become dispensable for the perpetuation of arthritis after delivery of IL-1, highlighting the contribution of this lineage to arthritis induction. These findings illuminate a mechanism by which mast cells can participate in the pathogenesis of autoimmune inflammatory arthritis and provide insights of potential relevance to human rheumatoid arthritis. PMID- 17277082 TI - Brain shape in human microcephalics and Homo floresiensis. AB - Because the cranial capacity of LB1 (Homo floresiensis) is only 417 cm(3), some workers propose that it represents a microcephalic Homo sapiens rather than a new species. This hypothesis is difficult to assess, however, without a clear understanding of how brain shape of microcephalics compares with that of normal humans. We compare three-dimensional computed tomographic reconstructions of the internal braincases (virtual endocasts that reproduce details of external brain morphology, including cranial capacities and shape) from a sample of 9 microcephalic humans and 10 normal humans. Discriminant and canonical analyses are used to identify two variables that classify normal and microcephalic humans with 100% success. The classification functions classify the virtual endocast from LB1 with normal humans rather than microcephalics. On the other hand, our classification functions classify a pathological H. sapiens specimen that, like LB1, represents an approximately 3-foot-tall adult female and an adult Basuto microcephalic woman that is alleged to have an endocast similar to LB1's with the microcephalic humans. Although microcephaly is genetically and clinically variable, virtual endocasts from our highly heterogeneous sample share similarities in protruding and proportionately large cerebella and relatively narrow, flattened orbital surfaces compared with normal humans. These findings have relevance for hypotheses regarding the genetic substrates of hominin brain evolution and may have medical diagnostic value. Despite LB1's having brain shape features that sort it with normal humans rather than microcephalics, other shape features and its small brain size are consistent with its assignment to a separate species. PMID- 17277083 TI - Thermodynamic analysis of progesterone receptor-promoter interactions reveals a molecular model for isoform-specific function. AB - Human progesterone receptors (PR) exist as two functionally distinct isoforms, PR A and PR-B. The proteins are identical except for an additional 164 residues located at the N terminus of PR-B. To determine the mechanisms responsible for isoform-specific functional differences, we present here a thermodynamic dissection of PR-A-promoter interactions and compare the results to our previous work on PR-B. This analysis has generated a number of results inconsistent with the traditional, biochemically based model of receptor function. Specifically, statistical models invoking preformed PR-A dimers as the active binding species demonstrate that intrinsic binding energetics are over an order of magnitude greater than is apparent. High-affinity binding is opposed, however, by a large energetic penalty. The consequences of this penalty are 2-fold: Successive monomer binding to a palindromic response element is thermodynamically favored over preformed dimer binding, and DNA-induced dimerization of the monomers is largely abolished. Furthermore, PR-A binding to multiple PREs is only weakly cooperative, as judged by a 5-fold increase in overall stability. Comparison of these results to our work on PR-B demonstrates that whereas both isoforms appear to have similar DNA binding affinities, PR-B in fact has a greatly increased intrinsic binding affinity and cooperative binding ability relative to PR-A. These differences thus suggest that residues unique to PR-B allosterically regulate the energetics of cooperative promoter assembly. From a functional perspective, the differences in microscopic affinities predict receptor-promoter occupancies that accurately correlate with the transcriptional activation profiles seen for each isoform. PMID- 17277080 TI - Transcriptomic analysis of growth heterosis in larval Pacific oysters (Crassostrea gigas). AB - Compared with understanding of biological shape and form, knowledge is sparse regarding what regulates growth and body size of a species. For example, the genetic and physiological causes of heterosis (hybrid vigor) have remained elusive for nearly a century. Here, we investigate gene-expression patterns underlying growth heterosis in the Pacific oyster (Crassostrea gigas) in two partially inbred (f = 0.375) and two hybrid larval populations produced by a reciprocal cross between the two inbred families. We cloned cDNA and generated 4.5 M sequence tags with massively parallel signature sequencing. The sequences contain 23,274 distinct signatures that are expressed at statistically nonzero levels and show a highly positively skewed distribution with median and modal counts of 9.25 million and 3 transcripts per million, respectively. For nearly half of these signatures, expression level depends on genotype and is predominantly nonadditive (hybrids deviate from the inbred average). Statistical contrasts suggest approximately 350 candidate genes for growth heterosis that exhibit concordant nonadditive expression in reciprocal hybrids; this represents only approximately 1.5% of the >20,000 transcripts. Patterns of gene expression, which include dominance for low expression and even underdominance of expression, are more complex than predicted from classical dominant or overdominant explanations of heterosis. Preliminary identification of ribosomal proteins among candidate genes supports the suggestion from previous studies that efficiency of protein metabolism plays a role in growth heterosis. PMID- 17277085 TI - Biosynthesis of gamma-butyrolactone autoregulators that switch on secondary metabolism and morphological development in Streptomyces. AB - A factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) is a representative of the gamma-butyrolactone autoregulators that trigger secondary metabolism and morphogenesis in the Gram-positive, filamentous bacterial genus Streptomyces. Here, we report the A factor biosynthesis pathway in Streptomyces griseus. The monomeric AfsA, containing a tandem repeat domain of approximately 80 aa, catalyzed beta-ketoacyl transfer from 8-methyl-3-oxononanoyl-acyl carrier protein to the hydroxyl group of dihydroxyacetone phosphate (DHAP), thus producing an 8-methyl-3-oxononanoyl-DHAP ester. The fatty acid ester was nonenzymatically converted to a butenolide phosphate by intramolecular aldol condensation. The butenolide phosphate was then reduced by BprA that was encoded just downstream of afsA. The phosphate group on the resultant butanolide was finally removed by a phosphatase, resulting in formation of A factor. The 8 methyl-3-oxononanoyl-DHAP ester produced by the action of AfsA was also converted to A factor in an alternative way; the phosphate group on the ester was first removed by a phosphatase and the dephosphorylated ester was converted nonenzymatically to a butenolide, which was then reduced by a reductase different from BprA, resulting in A factor. Because introduction of afsA alone into Escherichia coli caused the host to produce a substance having A factor activity, the reductase(s) and phosphatase(s) were not specific to the A factor biosynthesis but commonly present in bacteria. AfsA is thus the key enzyme for the biosynthesis of gamma-butyrolactones. PMID- 17277084 TI - Indirect activation of a plant nucleotide binding site-leucine-rich repeat protein by a bacterial protease. AB - Nucleotide binding site-leucine-rich repeat (NBS-LRR) proteins mediate pathogen recognition in both mammals and plants. The molecular mechanisms by which pathogen molecules activate NBS-LRR proteins are poorly understood. Here we show that RPS5, a NBS-LRR protein from Arabidopsis, is activated by AvrPphB, a bacterial protease, via an indirect mechanism. When transiently expressed in Nicotiana benthamiana leaves, full-length RPS5 protein triggered programmed cell death, but only when coexpressed with AvrPphB and a second Arabidopsis protein, PBS1, which is a specific substrate of AvrPphB. Using coimmunoprecipitation analysis, we found that PBS1 is in a complex with the N-terminal coiled coil (CC) domain of RPS5 before exposure to AvrPphB. Deletion of the RPS5 LRR domain caused RPS5 to constitutively activate programmed cell death, even in the absence of AvrPphB and PBS1, and this activation depended on both the CC and NBS domains. The LRR and CC domains both coimmunoprecipitate with the NBS domain but not with each other. Thus, the LRR domain appears to function in part to inhibit RPS5 signaling, and cleavage of PBS1 by AvrPphB appears to release RPS5 from this inhibition. An amino acid substitution in the NBS site of RPS5 that is known to inhibit ATP binding in other NBS-LRR proteins blocked activation of RPS5, whereas a substitution thought to inhibit ATP hydrolysis constitutively activated RPS5. Combined, these data suggest that ATP versus ADP binding functions as a molecular switch that is flipped by cleavage of PBS1. PMID- 17277086 TI - Role of the C terminus of the ribonucleotide reductase large subunit in enzyme regeneration and its inhibition by Sml1. AB - Ribonucleotide reductase maintains cellular deoxyribonucleotide pools and is thus tightly regulated during the cell cycle to ensure high fidelity in DNA replication. The Sml1 protein inhibits ribonucleotide reductase activity by binding to the R1 subunit. At the completion of each turnover cycle, the active site of R1 becomes oxidized and subsequently regenerated by a cysteine pair (CX2C) at its C-terminal domain (R1-CTD). Here we show that R1-CTD acts in trans to reduce the active site of its neighboring monomer. Both Sml1 and R1-CTD interact with the N-terminal domain of R1 (R1-NTD), which involves a conserved two-residue sequence motif in the R1-NTD. Mutations at these two positions enhancing the Sml1-R1 interaction cause SML1-dependent lethality. These results point to a model whereby Sml1 competes with R1-CTD for association with R1-NTD to hinder the accessibility of the CX2C motif to the active site for R1 regeneration. PMID- 17277087 TI - A novel major facilitator superfamily protein at the tonoplast influences zinc tolerance and accumulation in Arabidopsis. AB - Zinc (Zn) is an essential micronutrient required by all cells but is toxic in excess. We have identified three allelic Zn-sensitive mutants of Arabidopsis (Arabidopsis thaliana). The gene, designated ZINC-INDUCED FACILITATOR1 (ZIF1), encodes a member of the major facilitator superfamily of membrane proteins, which are found in all organisms and transport a wide range of small, organic molecules. Shoots of zif1 mutants showed increased accumulation of Zn but not other metal ions. In combination with mutations affecting shoot-to-root Zn translocation, zif1 hma2 hma4 triple mutants accumulated less Zn than the wild type but remained Zn sensitive, suggesting that the zif1 Zn-sensitive phenotype is due to altered Zn distribution. zif1 mutants were also more sensitive to cadmium but less sensitive to nickel. ZIF1 promoter-beta-glucuronidase fusions were expressed throughout the plant, with strongest expression in young tissues, and predominantly in the vasculature in older tissues. ZIF1 expression was highly induced by Zn and, to a lesser extent, by manganese. A ZIF1-green fluorescent protein fusion protein localized to the tonoplast in transgenic plants. MTP1 has been identified as a tonoplast Zn transporter and a zif1-1 mtp1-1 double mutant was more sensitive to Zn than either of the single mutants, suggesting ZIF1 influences a distinct mechanism of Zn homeostasis. Overexpression of ZIF1 conferred increased Zn tolerance and interveinal leaf chlorosis in some transgenic lines in which ZIF1 expression was high. We propose that ZIF1 is involved in a novel mechanism of Zn sequestration, possibly by transport of a Zn ligand or a Zn ligand complex into vacuoles. PMID- 17277088 TI - Diverse subcellular locations of cryptogein-induced reactive oxygen species production in tobacco Bright Yellow-2 cells. AB - Reactive oxygen species (ROS) play a crucial role in many cellular responses and signaling pathways, including the oxidative burst defense response to pathogens. We have examined very early events in cryptogein-induced ROS production in tobacco (Nicotiana tabacum) Bright Yellow-2 suspension cells. Using Amplex Red and Amplex Ultra Red reagents, which report real-time H2O2 accumulation in cell populations, we show that the internal signal for H2O2 develops more rapidly than the external apoplastic signal. Subcellular accumulation of H2O2 was also followed in individual cells using the 2',7'-dichlorofluorescein diacetate fluorescent probe. Major accumulation was detected in endomembrane, cytoplasmic, and nuclear compartments. When cryptogein was added, the signal developed first in the nuclear region and, after a short delay, in the cell periphery. Interestingly, isolated nuclei were capable of producing H2O2 in a calcium dependent manner, implying that nuclei can serve as a potential active source of ROS production. These results show complex spatial compartmentalization for ROS accumulation and an unexpected temporal sequence of events that occurs after cryptogein application, suggesting novel intricacy in ROS-signaling cascades. PMID- 17277089 TI - S-nitrosoglutathione reductase affords protection against pathogens in Arabidopsis, both locally and systemically. AB - Nitric oxide and S-nitrosothiols (SNOs) are widespread signaling molecules that regulate immunity in animals and plants. Levels of SNOs in vivo are controlled by nitric oxide synthesis (which in plants is achieved by different routes) and by S nitrosoglutathione turnover, which is mainly performed by the S nitrosoglutathione reductase (GSNOR). GSNOR is encoded by a single-copy gene in Arabidopsis (Arabidopsis thaliana; Martinez et al., 1996; Sakamoto et al., 2002). We report here that transgenic plants with decreased amounts of GSNOR (using antisense strategy) show enhanced basal resistance against Peronospora parasitica Noco2 (oomycete), which correlates with higher levels of intracellular SNOs and constitutive activation of the pathogenesis-related gene, PR-1. Moreover, systemic acquired resistance is impaired in plants overexpressing GSNOR and enhanced in the antisense plants, and this correlates with changes in the SNO content both in local and systemic leaves. We also show that GSNOR is localized in the phloem and, thus, could regulate systemic acquired resistance signal transport through the vascular system. Our data corroborate the data from other authors that GSNOR controls SNO in vivo levels, and shows that SNO content positively influences plant basal resistance and resistance-gene-mediated resistance as well. These data highlight GSNOR as an important and widely utilized component of resistance protein signaling networks conserved in animals and plants. PMID- 17277090 TI - Candidate genes and quantitative trait loci affecting fruit ascorbic acid content in three tomato populations. AB - Fresh fruit and vegetables are a major source of ascorbic acid (vitamin C), an important antioxidant for the human diet and also for plants. Ascorbic acid content in fruit exhibits a quantitative inheritance. Quantitative trait loci (QTL) for ascorbic acid content have been mapped in three tomato populations derived from crosses between cultivated tomato varieties (Solanum lycopersicum accessions) and three related wild species or subspecies. The first population consists of a set of introgression lines derived from Solanum pennellii, each containing a unique fragment of the wild species genome. The second population is an advanced backcross population derived from a cross between a cultivated tomato and a Solanum habrochaites (formerly Lycopersicum hirsutum) accession. The third population is a recombinant inbred line population derived from the cross between a cherry tomato line and a large fruited line. Common regions controlling ascorbic acid content have been identified on chromosomes 2, 8, 9, 10, and 12. In general, the wild alleles increased ascorbic acid content, but some improvement could also be provided by S. lycopersicum. Most QTLs appeared relatively stable over years and in different environments. Mapping of candidate genes involved in the metabolism of ascorbic acid has revealed a few colocations between genes and QTLs, notably in the case of a monodehydroascorbate reductase gene and a QTL present in two of the populations on chromosome 9 (bin 9-D), and a previously mapped GDP-mannose epimerase and a QTL on chromosome 9 (bin 9-J). PMID- 17277091 TI - Overexpression of pectin methylesterase inhibitors in Arabidopsis restricts fungal infection by Botrytis cinerea. AB - Pectin, one of the main components of plant cell wall, is secreted in a highly methylesterified form and is demethylesterified in muro by pectin methylesterase (PME). The action of PME is important in plant development and defense and makes pectin susceptible to hydrolysis by enzymes such as endopolygalacturonases. Regulation of PME activity by specific protein inhibitors (PMEIs) can, therefore, play a role in plant development as well as in defense by influencing the susceptibility of the wall to microbial endopolygalacturonases. To test this hypothesis, we have constitutively expressed the genes AtPMEI-1 and AtPMEI-2 in Arabidopsis (Arabidopsis thaliana) and targeted the proteins into the apoplast. The overexpression of the inhibitors resulted in a decrease of PME activity in transgenic plants, and two PME isoforms were identified that interacted with both inhibitors. While the content of uronic acids in transformed plants was not significantly different from that of wild type, the degree of pectin methylesterification was increased by about 16%. Moreover, differences in the fine structure of pectins of transformed plants were observed by enzymatic fingerprinting. Transformed plants showed a slight but significant increase in root length and were more resistant to the necrotrophic fungus Botrytis cinerea. The reduced symptoms caused by the fungus on transgenic plants were related to its impaired ability to grow on methylesterified pectins. PMID- 17277092 TI - Rapid classification of phenotypic mutants of Arabidopsis via metabolite fingerprinting. AB - We evaluated the application of gas chromatography-mass spectrometry metabolic fingerprinting to classify forward genetic mutants with similar phenotypes. Mutations affecting distinct metabolic or signaling pathways can result in common phenotypic traits that are used to identify mutants in genetic screens. Measurement of a broad range of metabolites provides information about the underlying processes affected in such mutants. Metabolite profiles of Arabidopsis (Arabidopsis thaliana) mutants defective in starch metabolism and uncharacterized mutants displaying a starch-excess phenotype were compared. Each genotype displayed a unique fingerprint. Statistical methods grouped the mutants robustly into distinct classes. Determining the genes mutated in three uncharacterized mutants confirmed that those clustering with known mutants were genuinely defective in starch metabolism. A mutant that clustered away from the known mutants was defective in the circadian clock and had a pleiotropic starch-excess phenotype. These results indicate that metabolic fingerprinting is a powerful tool that can rapidly classify forward genetic mutants and streamline the process of gene discovery. PMID- 17277093 TI - A novel ankyrin-repeat membrane protein, IGN1, is required for persistence of nitrogen-fixing symbiosis in root nodules of Lotus japonicus. AB - Nitrogen-fixing symbiosis of legume plants with Rhizobium bacteria is established through complex interactions between two symbiotic partners. Similar to the mutual recognition and interactions at the initial stages of symbiosis, nitrogen fixation activity of rhizobia inside root nodules of the host legume is also controlled by specific interactions during later stages of nodule development. We isolated a novel Fix(-) mutant, ineffective greenish nodules 1 (ign1), of Lotus japonicus, which forms apparently normal nodules containing endosymbiotic bacteria, but does not develop nitrogen fixation activity. Map-based cloning of the mutated gene allowed us to identify the IGN1 gene, which encodes a novel ankyrin-repeat protein with transmembrane regions. IGN1 expression was detected in all organs of L. japonicus and not enhanced in the nodulation process. Immunoanalysis, together with expression analysis of a green fluorescent protein IGN1 fusion construct, demonstrated localization of the IGN1 protein in the plasma membrane. The ign1 nodules showed extremely rapid premature senescence. Irregularly enlarged symbiosomes with multiple bacteroids were observed at early stages (8-9 d post inoculation) of nodule formation, followed by disruption of the symbiosomes and disintegration of nodule infected cell cytoplasm with aggregation of the bacteroids. Although the exact biochemical functions of the IGN1 gene are still to be elucidated, these results indicate that IGN1 is required for differentiation and/or persistence of bacteroids and symbiosomes, thus being essential for functional symbiosis. PMID- 17277094 TI - EpsinR2 interacts with clathrin, adaptor protein-3, AtVTI12, and phosphatidylinositol-3-phosphate. Implications for EpsinR2 function in protein trafficking in plant cells. AB - Members of the epsin family of proteins (epsins) are characterized by the presence of an epsin N-terminal homology (ENTH) domain. Epsins have been implicated in various protein-trafficking pathways in animal and yeast (Saccharomyces cerevisiae) cells. Plant cells also contain multiple epsin-related proteins. In Arabidopsis (Arabidopsis thaliana), EPSIN1 is involved in vacuolar trafficking of soluble proteins. In this study, we investigated the role of Arabidopsis EpsinR2 in protein trafficking in plant cells. EpsinR2 contains a highly conserved ENTH domain but a fairly divergent C-terminal sequence. We found that the N-terminal ENTH domain specifically binds to phosphatidylinositol-3-P in vitro and has a critical role in the targeting of EpsinR2. Upon transient expression in protoplasts, hemagglutinin epitope-tagged EpsinR2 was translocated primarily to a novel cellular compartment, while a minor portion localized to the Golgi complex. Protein-binding experiments showed that EpsinR2 interacts with clathrin, AtVTI12, and the Arabidopsis homologs of adaptor protein-3 delta adaptin and adaptor protein-2 alpha-adaptin. Localization experiments revealed that hemagglutinin epitope-tagged EpsinR2 colocalizes primarily with delta adaptin and partially colocalizes with clathrin and AtVTI12. Based on these findings, we propose that EpsinR2 plays an important role in protein trafficking through interactions with delta-adaptin, AtVTI12, clathrin, and phosphatidylinositol-3-P. PMID- 17277095 TI - Cytokinin import rate as a signal for photosynthetic acclimation to canopy light gradients. AB - Plants growing in dense canopies are exposed to vertical light gradients and show photosynthetic acclimation at the whole-plant level, resulting in efficient photosynthetic carbon gain. We studied the role of cytokinins transported through the transpiration stream as one of probably multiple signals for photosynthetic acclimation to light gradients using both tobacco (Nicotiana tabacum) and Arabidopsis (Arabidopsis thaliana). We show that substantial variation in leaf transpiration parallels the light gradient in tobacco canopies and experimental reduction of the transpiration rate of a leaf, independent of light, is sufficient to reduce photosynthetic capacity in both species, as well as transcript levels of the small subunit of Rubisco (rbcS) gene in Arabidopsis. Mass spectrometric analysis of xylem sap collected from intact, transpiring tobacco plants revealed that shaded leaves import less cytokinin than leaves exposed to high light. In Arabidopsis, reduced transpiration rate of a leaf in the light is associated with lower cytokinin concentrations, including the bioactive trans-zeatin and trans-zeatin riboside, as well as reduced expression of the cytokinin-responsive genes ARR7 and ARR16. External application of cytokinin to shaded leaves rescued multiple shade effects, including rbcS transcript levels in both species, as did locally induced cytokinin overproduction in transgenic tobacco plants. From these data, we conclude that light gradients over the foliage of a plant result in reduced cytokinin activity in shaded leaves as a consequence of reduced import through the xylem and that cytokinin is involved in the regulation of whole-plant photosynthetic acclimation to light gradients in canopies. PMID- 17277096 TI - Feedback regulation of xylem cytokinin content is conserved in pea and Arabidopsis. AB - Increased-branching mutants of garden pea (Pisum sativum; ramosus [rms]) and Arabidopsis (Arabidopsis thaliana; more axillary branches) were used to investigate control of cytokinin export from roots in relation to shoot branching. In particular, we tested the hypothesis that regulation of xylem sap cytokinin is dependent on a long-distance feedback signal moving from shoot to root. With the exception of rms2, branching mutants from both species had greatly reduced amounts of the major cytokinins zeatin riboside, zeatin, and isopentenyl adenosine in xylem sap compared with wild-type plants. Reciprocally grafted mutant and wild-type Arabidopsis plants gave similar results to those observed previously in pea, with xylem sap cytokinin down-regulated in all graft combinations possessing branched shoots, regardless of root genotype. This long distance feedback mechanism thus appears to be conserved between pea and Arabidopsis. Experiments with grafted pea plants bearing two shoots of the same or different genotype revealed that regulation of root cytokinin export is probably mediated by an inhibitory signal. Moreover, the signaling mechanism appears independent of the number of growing axillary shoots because a suppressed axillary meristem mutation that prevents axillary meristem development at most nodes did not abolish long-distance regulation of root cytokinin export in rms4 plants. Based on double mutant and grafting experiments, we conclude that RMS2 is essential for long-distance feedback regulation of cytokinin export from roots. Finally, the startling disconnection between cytokinin content of xylem sap and shoot tissues of various rms mutants indicates that shoots possess powerful homeostatic mechanisms for regulation of cytokinin levels. PMID- 17277097 TI - Overproduction of abscisic acid in tomato increases transpiration efficiency and root hydraulic conductivity and influences leaf expansion. AB - Overexpression of genes that respond to drought stress is a seemingly attractive approach for improving drought resistance in crops. However, the consequences for both water-use efficiency and productivity must be considered if agronomic utility is sought. Here, we characterize two tomato (Solanum lycopersicum) lines (sp12 and sp5) that overexpress a gene encoding 9-cis-epoxycarotenoid dioxygenase, the enzyme that catalyzes a key rate-limiting step in abscisic acid (ABA) biosynthesis. Both lines contained more ABA than the wild type, with sp5 accumulating more than sp12. Both had higher transpiration efficiency because of their lower stomatal conductance, as demonstrated by increases in delta(13)C and delta(18)O, and also by gravimetric and gas-exchange methods. They also had greater root hydraulic conductivity. Under well-watered glasshouse conditions, mature sp5 plants were found to have a shoot biomass equal to the wild type despite their lower assimilation rate per unit leaf area. These plants also had longer petioles, larger leaf area, increased specific leaf area, and reduced leaf epinasty. When exposed to root-zone water deficits, line sp12 showed an increase in xylem ABA concentration and a reduction in stomatal conductance to the same final levels as the wild type, but from a different basal level. Indeed, the main difference between the high ABA plants and the wild type was their performance under well-watered conditions: the former conserved soil water by limiting maximum stomatal conductance per unit leaf area, but also, at least in the case of sp5, developed a canopy more suited to light interception, maximizing assimilation per plant, possibly due to improved turgor or suppression of epinasty. PMID- 17277098 TI - AGF1, an AT-hook protein, is necessary for the negative feedback of AtGA3ox1 encoding GA 3-oxidase. AB - Negative feedback is a fundamental mechanism of organisms to maintain the internal environment within tolerable limits. Gibberellins (GAs) are essential regulators of many aspects of plant development, including seed germination, stem elongation, and flowering. GA biosynthesis is regulated by the feedback mechanism in plants. GA 3-oxidase (GA3ox) catalyzes the final step of the biosynthetic pathway to produce the physiologically active GAs. Here, we found that only the AtGA3ox1 among the AtGA3ox family of Arabidopsis (Arabidopsis thaliana) is under the regulation of GA-negative feedback. We have identified a cis-acting sequence responsible for the GA-negative feedback of AtGA3ox1 using transgenic plants. Furthermore, we have identified an AT-hook protein, AGF1 (for the AT-hook protein of GA feedback regulation), as a DNA-binding protein for the cis-acting sequence of GA-negative feedback. The mutation in the cis-acting sequence abolished both GA-negative feedback and AGF1 binding. In addition, constitutive expression of AGF1 affected GA-negative feedback in Arabidopsis. Our results suggest that AGF1 plays a role in the homeostasis of GAs through binding to the cis-acting sequence of the GA-negative feedback of AtGA3ox1. PMID- 17277099 TI - Unique human tumor antigens: immunobiology and use in clinical trials. AB - The individual, unique tumor Ags, which characterize each single tumor, were described 50 years ago in rodents but their molecular characterization was limited to few of them and obtained during the last 20 years. Here we summarize the evidence for the existence and the biological role of such Ags in human tumors, although such evidence was provided only during the last 10 years and by a limited number of studies, a fact leading to a misrepresentation of unique Ags in human tumor immunology. This was also due to the increasing knowledge on the shared, self-human tumor Ags, which have been extensively used as cancer vaccines. In this review, we highlight the biological and clinical importance of unique Ags and suggest how they could be used in clinical studies aimed at assessing their immunogenic and clinical potential both in active and adoptive immunotherapy of human tumors. PMID- 17277100 TI - The PI3K p110delta is required for down-regulation of RAG expression in immature B cells. AB - At the immature B cell stage the BCR signals the down-regulation of the RAG genes and Ig L chain (LC) allelic and isotype exclusion. The signaling pathway that regulates these events is poorly characterized. We demonstrate that immature B cells from mice deficient in the PI3K catalytic subunit p110delta fail to suppress RAG expression and inappropriately recombine kappa and lambda LC loci. In addition, in the presence of the autoantigen, clonal deletion and receptor editing still takes place, demonstrating that these processes are independent of p110delta. These results demonstrate a role for p110delta in the regulation of RAG gene expression and thereby LC allelic/isotype exclusion. PMID- 17277101 TI - Loss of TLR2, TLR4, and TLR5 on Langerhans cells abolishes bacterial recognition. AB - It is unknown whether closely related epidermal dendritic cells, Langerhans cells (LCs), and dermal dendritic cells (DDCs) have unique functions. In this study, we show that human DDCs have a broad TLR expression profile, whereas human LCs have a selective impaired expression of cell surface TLR2, TLR4, and TLR5, all involved in bacterial recognition. This distinct TLR expression profile is acquired during the TGF-beta1-driven development of LCs in vitro. Consequently, and in contrast to DDCs, LCs weakly respond to bacterial TLR2, TLR4, and TLR5 ligands in terms of cytokine production and maturation, as well as to whole Gram positive and Gram-negative bacteria, whereas their responsiveness to viral TLR ligands and viruses is fully active and comparable to DDCs. Unresponsiveness of LCs to bacteria may be a mechanism that contributes to tolerance to bacterial commensals that colonize the skin. PMID- 17277102 TI - Non-T cell activation linker (NTAL) negatively regulates TREM-1/DAP12-induced inflammatory cytokine production in myeloid cells. AB - The engagement of triggering receptor expressed on myeloid cells 1 (TREM-1) on macrophages and neutrophils leads to TNF-alpha and IL-8 production and enhances inflammatory responses to microbial products. For signal transduction, TREM-1 couples to the ITAM-containing adapter DNAX activation protein of 12 kDa (DAP12). In general, ITAM-mediated signals lead to cell activation, although DAP12 was recently implicated in inhibitory signaling in mouse macrophages and dendritic cells. To date, signals downstream of the TREM-1 and DAP12 complex in myeloid cells are poorly defined. By analyzing receptor-induced tyrosine phosphorylation patterns, we discovered that the ligation of TREM-1 leads to tyrosine phosphorylation of the non-T cell activation linker (NTAL; also called linker of activation in B cells or LAB) in a myelomonocytic cell line and primary human granulocytes. Using RNA interference to decrease the expression levels of NTAL, we demonstrate that in NTAL knockdown cell lines the phosphorylation of ERK1/2 is enhanced. In addition, low levels of NTAL are correlated with decreased and delayed mobilization of Ca(2+) after TREM-1 triggering. Most importantly, we demonstrate that NTAL acts as a negative regulator of TNF-alpha and IL-8 production after stimulation via TREM-1. Our results show that activation signals delivered via DAP12 can be counterbalanced by the adaptor NTAL, identifying NTAL as gatekeeper of TREM-1/DAP12-induced signaling in myeloid cells. PMID- 17277103 TI - Distinct differentiation potential of blood monocyte subsets in the lung. AB - Peripheral blood monocytes are a population of circulating mononuclear phagocytes that harbor potential to differentiate into macrophages and dendritic cells. As in humans, monocytes in the mouse comprise two phenotypically distinct subsets that are Gr1(high)CX(3)CR1(int) and Gr1(low)CX(3)CR1(high), respectively. The question remains whether these populations contribute differentially to the generation of peripheral mononuclear phagocytes. In this study, we track the fate of adoptively transferred, fractionated monocyte subsets in the lung of recipient mice. We show that under inflammatory and noninflammatory conditions, both monocyte subsets give rise to pulmonary dendritic cells. In contrast, under the conditions studied, only Gr1(low)CX(3)CR1(high) monocytes, but not Gr1(high)CX(3)CR1(int) cells, had the potential to differentiate into lung macrophages. However, Gr1(high)CX(3)CR1(int) monocytes could acquire this potential upon conversion into Gr1(low)CX(3)CR1(high) cells. Our results therefore indicate an intrinsic dichotomy in the differentiation potential of the two main blood monocyte subsets. PMID- 17277105 TI - IL-2 is essential for TGF-beta to convert naive CD4+CD25- cells to CD25+Foxp3+ regulatory T cells and for expansion of these cells. AB - IL-2 and TGF-beta both have important roles in the induction and maintenance of immunologic tolerance, but whether these cytokines act separately or together to achieve this effect is poorly understood. Although others have reported that IL-2 can directly enhance forkhead box protein P3 (Foxp3) transcription factor expression by natural CD4(+)CD25(+) regulatory T cells, in this study, we report that the role of IL-2 on the generation of peripheral regulatory CD4(+) cells is indirect. Ab neutralization studies and experiments with IL-2-deficient mice have revealed that IL-2 is required for TGF-beta to induce naive CD4(+)CD25(-) cells to become CD25(+) and express Foxp3, and develop the characteristic properties of CD4(+)CD25(+) regulatory cells. This effect of IL-2 on the generation and expansion of these adaptive Foxp3(+) regulatory cells is nonredundant, but IL-4, IL-7, and IL-15, other common gamma-chain cytokines, could sustain Foxp3 expression. Because subjects with autoimmune diseases often have defects in the production of IL-2 and/or TGF-beta, the generation of autologous T regulatory cells ex vivo with these cytokines for transfer in vivo may have considerable therapeutic potential. PMID- 17277104 TI - Selective thymus settling regulated by cytokine and chemokine receptors. AB - To generate T cells throughout adult life, the thymus must import hemopoietic progenitors from the bone marrow via the blood. In this study, we establish that thymus settling is selective. Using nonirradiated recipient mice, we found that hemopoietic stem cells were excluded from the thymus, whereas downstream multipotent progenitors (MPP) and common lymphoid progenitors rapidly generated T cells following i.v. transfer. This cellular specificity correlated with the expression of the chemokine receptor CCR9 by a subset of MPP and common lymphoid progenitors but not hemopoietic stem cells. Furthermore, CCR9 expression was required for efficient thymus settling. Finally, we demonstrate that a prethymic signal through the cytokine receptor fms-like tyrosine kinase receptor-3 was required for the generation of CCR9-expressing early lymphoid progenitors, which were the most efficient progenitors of T cells within the MPP population. We conclude that fms-like tyrosine kinase receptor-3 signaling is required for the generation of T lineage-competent progenitors, which selectively express molecules, including CCR9, that allow them to settle within the thymus. PMID- 17277106 TI - Imatinib mesylate inhibits antigen-specific memory CD8 T cell responses in vivo. AB - Imatinib mesylate (IM) is effective at inducing complete cytogenetic remission in patients with chronic myelogenous leukemia. Because its influence on CD8 T cell responsiveness in vivo is unknown, we investigated the effects of IM by analyzing the response of OT-1 CD8 T cells to Listeria monocytogenes (LM) that express the cognate epitope OVA(257-264) (LM-OVA). In vitro, IM had no effect on Ag-specific expansion, cell division, cell cycle progression, or IFN-gamma expression in naive or memory OT-1 T cells. However, IM induced apoptosis of naive and memory OT-1 T cells at doses of >5 microM. At 15 microM IM, OT-1 T cells did not survive in in vitro cultures. The primary response of OT-1 T cells in vivo to LM-OVA infection was unaltered. In contrast, continuous IM treatment resulted in a diminished memory OT-1 response. The expression of IL-7Ralpha, a receptor required for memory cell survival, was lower (on OT-1 cells) in animals receiving IM. These results indicate that IM treatment affects the ability of the CD8 memory pool to respond to Ag and has the potential to increase susceptibility to infection. PMID- 17277108 TI - Differential CD40/CD40L expression results in counteracting antitumor immune responses. AB - Establishment of host-protective memory T cells against tumors is the objective of an antitumor immunoprophylactic strategy such as reinforcing T cell costimulation via CD40-CD40L interaction. Previous CD40-targeted strategies assumed that T cell costimulation is an all-or-none phenomenon. It was unknown whether different levels of CD40L expression induce quantitatively and qualitatively different effector T cell responses. Using mice expressing different levels of CD40L, we demonstrated that the greater the T cell CD40L expression the less tumor growth occurred; the antitumor T cell response was host protective. Lower levels of CD40L expression on T cells induced IL-10-mediated suppression of tumor-regressing effector CD8(+) T cells and higher productions of IL-4 and IL-10. Using mice expressing different levels of CD40 or by administering different doses of anti-CD40 Ab, similar observations were recorded implying that the induction of protumor or antitumor T cell responses was a function of the extent of CD40 cross-linking. IL-10 neutralization during priming with tumor Ags resulted in a stronger tumor-regressing effector T cell response. Using IL-10(-/-) DC for priming of mice expressing different levels of CD40L and subsequent transfer of the T cells from the primed mice to nu/nu mice, we demonstrated the protumor role of IL-10 in the induction of tumor-promoting T cells. Our results demonstrate that a dose-dependent cross-linking of a costimulatory molecule dictates the functional phenotype of the elicited effector T cell response. The T cell costimulation is a continuum of a function that induces not only graded T cell responses but also two counteracting responses at two extremes. PMID- 17277107 TI - Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin alphaMbeta2. AB - Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal disease in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is of critical importance in host defense and the prime task of cells of the innate immune system. We previously demonstrated that the integrin alpha(M)beta(2) (CD11b/CD18) is the major leukocyte receptor involved in C. albicans recognition, mediating both adhesive and migratory responses to the fungus. In the present study, we demonstrate that various C. albicans strains release a protease-sensitive activity into their conditioned medium that supports alpha(M)beta(2)-mediated cell adhesion and migration. The isolation and characterization of this protein was undertaken by two independent approaches: 1) immunoaffinity purification on a mAb raised to conditioned medium which blocked alpha(M)beta(2)-dependent adhesion and migration; and 2) affinity chromatography on purified alpha(M)beta(2). Each approach led to the isolation of the same protein, which was unequivocally identified as pH-regulated Ag 1 (Pra1p), based on mass spectrometry and amino acid sequence analyses. C. albicans mutant strains lacking Pra1p were unable to support leukocyte adhesion or migration. In a neutrophil-mediated fungal killing assay, such mutant strains were resistant to killing and/or phagocytosis. Addition of purified Pra1p or reagents that block alpha(M)beta(2) function prevented killing of Pra1p-expressing but not Pra1p-deficient strains of C. albicans. Together, these data indicate that Pra1p is a ligand of alpha(M)beta(2) on C. albicans and that the soluble form of Pra1p may assist the fungus in escaping host surveillance. PMID- 17277109 TI - Changes in the role of the CD45 protein tyrosine phosphatase in regulating Lck tyrosine phosphorylation during thymic development. AB - CD45-dependent dephosphorylation of the negative regulatory C-terminal tyrosine of the Src family kinase Lck, promotes efficient TCR signal transduction. However, despite the role of CD45 in positively regulating Lck activity, the distinct phenotypes of CD45 and Lck/Fyn-deficient mice suggest that the role of CD45 in promoting Lck activity may be differentially regulated during thymocyte development. In this study, we have found that the C-terminal tyrosine of Lck (Y505) is markedly hyperphosphorylated in total thymocytes from CD45-deficient mice compared with control animals. In contrast, regulation of the Lck Y505 phosphorylation in purified, double-negative thymocytes is relatively unaffected in CD45-deficient cells. These changes in the role of CD45 in regulating Lck phosphorylation during thymocyte development correlate with changes in coreceptor expression and the presence of coreceptor-associated Lck. Biochemical analysis of coreceptor-associated and nonassociated Lck in thymocytes, and in cell lines varying in CD4 and CD45 expression, indicate that CD45-dependent regulation of Lck Y505 phosphorylation is most evident within the fraction of Lck that is coreceptor associated. In contrast, Lck Y505 phosphorylation that is not coreceptor associated is less affected by the absence of CD45. These data define distinct pools of Lck that are differentially regulated by CD45 during T cell development. PMID- 17277110 TI - Francisella tularensis-infected macrophages release prostaglandin E2 that blocks T cell proliferation and promotes a Th2-like response. AB - Francisella tularensis is a highly infectious bacterial pathogen, and is likely to have evolved strategies to evade and subvert the host immune response. In this study, we show that F. tularensis infection of macrophages alters T cell responses in vitro, by blocking T cell proliferation and promoting a Th2-like response. We demonstrate that a soluble mediator is responsible for this effect and identify it as PGE(2). Supernatants from F. tularensis-infected macrophages inhibited IL-2 secretion from both MHC class I and MHC class II-restricted T cell hybridomas, as well as enhanced a Th2-like response by inducing increased production of IL-5. Furthermore, the soluble mediator blocked proliferation of naive MHC class I-restricted T cells when stimulated with cognate tetramer. Indomethacin treatment partially restored T cell proliferation and lowered IL-5 production to wild-type levels. Macrophages produced PGE(2) when infected with F. tularensis, and treatment of infected macrophages with indomethacin, a cyclooxygenase-1/cyclooxygenase-2 inhibitor, blocked PGE(2) production. To further demonstrate that PGE(2) was responsible for skewing of T cell responses, we infected macrophages from membrane PGE synthase 1 knockout mice (mPGES1(-/-)) that cannot produce PGE(2). Supernatants from F. tularensis-infected membrane PGE synthase 1(-/-) macrophages did not inhibit T cell proliferation. Furthermore, treatment of T cells with PGE(2) recreated the effects seen with infected supernatant. From these data, we conclude that F. tularensis can alter host T cell responses by causing macrophages to produce PGE(2). This study defines a previously unknown mechanism used by F. tularensis to modulate adaptive immunity. PMID- 17277111 TI - Stromal derived growth factor-1alpha: another mediator in neural-emerging immune system through Tac1 expression in bone marrow stromal cells. AB - Stromal cell-derived growth factor-1alpha (SDF-1alpha) is a member of the CXC chemokines and interacts with the G protein, seven-transmembrane CXCR4 receptor. SDF-1alpha acts as a chemoattractant for immune and hemopoietic cells. The Tac1 gene encodes peptides belonging to the tachykinin family with substance P being the predominant member. Both SDF-1alpha and Tac1 peptides are relevant hemopoietic regulators. This study investigated the effects of SDF-1alpha on Tac1 expression in the major hemopoietic supporting cells, the bone marrow stroma, and addresses the consequence to hemopoiesis. Reporter gene assays with the 5' flanking region of Tac1 showed a bell-shaped effect of SDF-1alpha on luciferase activity with 20 ng/ml SDF-1alpha acting as stimulator, whereas 50 and 100 ng/ml SDF-1alpha acted as inhibitors. Gel shift assays and transfection with wild-type and mutant IkappaB indicate NF-kappaB as a mediator in the repressive effects at 50 and 100 ng/ml SDF-1alpha. Northern analyses and ELISA showed correlations among reporter gene activities, mRNA (beta-preprotachykinin I), and protein levels for substance P. Of relevance is the novel finding by long-term culture initiating cell assays that showed an indirect effect of SDF-1alpha on hemopoiesis through substance P production. The results also showed neurokinin 1 and not neurokinin 2 as the relevant receptor. Another crucial finding is that substance P does not regulate the production of SDF-1alpha in stroma. The studies indicate that SDF-1alpha levels above baseline production in bone marrow stroma induce the production of substance P to stimulate hemopoiesis. Substance P, however, does not act as autocrine stimulator to induce the production of SDF 1alpha. This study adds SDF-1alpha as a mediator within the neural-immune hemopoietic axis. PMID- 17277112 TI - Type I IFN-producing CD4 Valpha14i NKT cells facilitate priming of IL-10 producing CD8 T cells by hepatocytes. AB - Upon entering the liver CD8 T cells encounter large numbers of NKT cells patrolling the hepatocyte (HC) surface facing the perisinusoidal space. We asked whether hepatic NKT cells modulate the priming of CD8 T cells by HC. Hepatic (alpha-galactosyl-ceramide-loaded CD1d dimer binding) NKT cells produce predominantly IL-4 when stimulated with glycolipid-presenting HC but predominantly IFN-gamma when stimulated with glycolipid-presenting dendritic cells. These NKT cells prime naive CD8 T cells to a (K(b)-presented) peptide ligand if they simultaneously recognize a CD1d-binding glycolipid presented to them on the surface of the responding CD8 T cells that they prime. No IL-10 producing CD8 T cells are detected if these T cells are primed by either HC or NKT cells. In contrast, IL-10 is produced by HC-primed CD8 T cells if IFN-beta producing NKT cells are coactivated by the same HC presenting a glycolipid (in the context of CD1d) and an antigenic peptide (in the context of K(b)). Hence, IL 10-producing CD8 T cells are generated in a type I IFN-dependent manner if the three cell types (CD8 T cells, NKT cells, and ligand-presenting HC) specifically and closely interact. IL-10-producing CD8 T cells generated under these conditions down-modulate IL-2 (and proliferative) responses of naive CD4 or CD8 T cells primed by DC. If in close proximity, NKT cells can thus locally modulate the phenotype of CD8 T cells during their priming by HC thereby limiting the local activation of proinflammatory immune effector cells and protecting the liver against immune injury. PMID- 17277113 TI - Cognate CD4+ help elicited by resting dendritic cells does not impair the induction of peripheral tolerance in CD8+ T cells. AB - Peripheral tolerance is required to prevent autoimmune tissue destruction by self reactive T cells that escape negative selection in the thymus. One mechanism of peripheral tolerance in CD8(+) T cells is their activation by resting dendritic cells (DC). In contrast, DC can be "licensed" by CD4(+) T cells to induce cytotoxic function in CD8(+) T cells. The question that then arises, whether CD4(+) T cell help could impair peripheral tolerance induction in self-reactive CD8(+) T cells, has not been addressed. In this study we show that CD4(+) T cell activation by resting DC results in helper function that transiently promotes the expansion and differentiation of cognate CD8(+) T cells. However, both the CD4(+) and CD8(+) T cell populations ultimately undergo partial deletion and acquire Ag unresponsiveness, disabling their ability to destroy OVA-expressing pancreatic beta cells and cause diabetes. Thus, effective peripheral tolerance can be induced by resting DC in the presence of CD4(+) and CD8(+) T cells with specificity for the same Ag. PMID- 17277114 TI - CD18 is required for intestinal T cell responses at multiple immune checkpoints. AB - The intestinal immune response to oral Ags involves a complex multistep process. The requirements for optimal intestinal T cell responses in this process are unclear. LFA-1 plays a critical role in peripheral T cell trafficking and activation, however, its role in intestinal immune responses has not been precisely defined. To dissect the role of LFA-1 in intestinal immune responses, we used a system that allows for segregation of T cell migration and activation through the adoptive transfer of LFA-1-deficient (CD18(-/-)) CD4(+) T cells from DO11.10 TCR transgenic mice into wild-type BALB/c mice. We find that wild-type mice adoptively transferred with CD18(-/-) DO11.10 CD4(+) T cells demonstrate decreases in the numbers of Ag-specific T cells in the intestinal lamina propria after oral Ag administration. We also find that in addition to its role in trafficking to intestinal secondary lymphoid organs, LFA-1 is required for optimal CD4(+) T cell proliferation in vivo upon oral Ag immunization. Furthermore, CD18(-/-) DO11.10 CD4(+) T cells primed in the intestinal secondary lymphoid organs demonstrate defects in up-regulation of the intestinal-specific trafficking molecules, alpha(4)beta(7) and CCR9. Interestingly, the defect in trafficking of CD18(-/-) DO11.10 CD4(+) T cells to the intestinal lamina propria persists even under conditions of equivalent activation and intestinal-tropic differentiation, implicating a role for CD18 in the trafficking of activated T cells into intestinal tissues independent of the earlier defects in the intestinal immune response. This argues for a complex role for CD18 in the early priming checkpoints and ultimately in the trafficking of T cells to the intestinal tissues during an intestinal immune response. PMID- 17277115 TI - Regulation of CD8+ T lymphocyte effector function and macrophage inflammatory cytokine production by retinoic acid receptor gamma. AB - Vitamin A and its derivatives regulate a broad array of immune functions. The effects of these retinoids are mediated through members of retinoic acid receptors (RARs) and retinoid X receptors. However, the role of individual retinoid receptors in the pleiotropic effects of retinoids remains unclear. To dissect the role of these receptors in the immune system, we analyzed immune cell development and function in mice conditionally lacking RARgamma, the third member of the RAR family. We show that RARgamma is dispensable for T and B lymphocyte development, the humoral immune response to a T-dependent Ag and in vitro Th cell differentiation. However, RARgamma-deficient mice had a defective primary and memory CD8(+) T cell response to Listeria monocytogenes infection. Unexpectedly, RARgamma-deficient macrophages exhibited impaired inflammatory cytokine production upon TLR stimulation. These results suggest that under physiological condition, RARgamma is a positive regulator of inflammatory cytokine production. PMID- 17277116 TI - Peroxisome proliferator-activated receptor gamma control of dendritic cell function contributes to development of CD4+ T cell anergy. AB - There is increasing evidence that dendritic cell (DC) immunogenicity is not only positively regulated by ligands of pattern recognition receptors, but also negatively by signals that prevent DC activation and full functional maturation. Depending on their activation status, DCs can induce either immunity or tolerance. In this study, we provide molecular evidence that the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) is a negative regulator of DC maturation and function. Sustained PPARgamma activation in murine DCs reduced maturation-induced expression of costimulatory molecules and IL-12, and profoundly inhibited their capacity to prime naive CD4(+) T cells in vitro. Using PPARgamma-deficient DCs, generated by Cre-mediated ablation of the PPARgamma gene, agonist-mediated suppression of maturation-induced functional changes were abrogated. Moreover, absence of PPARgamma increased DC immunogenicity, suggesting a constitutive regulatory function of PPARgamma in DCs. Adoptive transfer of PPARgamma-activated Ag-presenting DCs induced CD4(+) T cell anergy, characterized by impaired differentiation resulting in absent Th1 and Th2 cytokine production and failure of secondary clonal expansion upon restimulation. Collectively, our data support the notion that PPARgamma is an efficient regulator of DC immunogenicity that may be exploited to deliberately target CD4(+) T cell-mediated immune responses. PMID- 17277117 TI - High IFN-gamma production of individual CD8 T lymphocytes is controlled by CD152 (CTLA-4). AB - CD8 T cell expansion and cytokine production is needed to generate an effective defense against viral invasion of the host. These features of CD8 T lymphocytes are regulated, especially during primary responses, by positive and negative costimulation. We show in this study that surface expression of CD152 is highly up-regulated on activated CD8 T lymphocytes during primary immune responses, suggesting a prominent regulatory role. Indeed, production of the proinflammatory cytokine IFN-gamma, but not TNF-alpha, by CD8 T cells was inhibited by CD152 engagement. The inhibition was regulated independent of proliferation and IL-2 production, but dependent on the quality of the TCR signaling. We show that signals induced by CD152 on activated CD8 T lymphocytes reduce the frequency of IFN-gamma(high)-expressing cells. Our data also show that in activated CD8 T cells, the CD152-mediated inhibition of cytokine production is more pronounced than inhibition of their proliferation. PMID- 17277118 TI - NK3-like NK cells are involved in protective effect of polyinosinic-polycytidylic acid on type 1 diabetes in nonobese diabetic mice. AB - Type 1 diabetes in NOD mice is characterized by the uncontrolled Th1 immune responses and deficiency of regulatory or suppressor cells. Previous study has shown that NOD mice treated with polyinosinic-polycytidylic acid (poly(I:C)) have a markedly reduced incidence of diabetes, but the underlying mechanisms remain unclear. In this study, we report that the prevention of diabetes by poly(I:C) is associated with the formation of Th2-enriched environment in spleen and pancreas. We further show that the prevention of diabetes and the formation of Th2-enriched environment depend on the presence of NK cells. Long-term poly(I:C)-treated NK cells exhibit a NK3-like phenotype, and are involved in the induction of Th2 bias of spleen cells in response to islet autoantigens via TGF-beta-dependent manner. Therefore, NK cells mediate the protective effect of poly(I:C) possibly through the promotion of Th2 bias of immune responses. These findings suggest that NK cells can participate in the regulation of autoimmune diabetes. PMID- 17277119 TI - Selective use of TRAM in lipopolysaccharide (LPS) and lipoteichoic acid (LTA) induced NF-kappaB activation and cytokine production in primary human cells: TRAM is an adaptor for LPS and LTA signaling. AB - TLR signal via Toll-IL-1R (TIR) homology domain-containing adaptor proteins. One of these adaptors, Toll-IL-1R domain-containing adaptor inducing IFN-beta-related adaptor molecule (TRAM), has been shown to be essential for TLR4 signaling in TRAM(-/-) mice and cell lines. Previously, we showed that MyD88 or Mal dominant negative constructs did not inhibit LPS induction of cytokines in primary human M CSF-derived macrophages. A possible explanation was redundancy of the adaptors during LPS signaling. TRAM is a suitable candidate to compensate for these adaptors. To investigate a potential role for TRAM in LPS signaling in human M CSF-derived macrophages, we engineered an adenoviral construct expressing dominant-negative TRAM-C117H (AdTRAMdn). Synovial fibroblasts (SF) and human umbilical endothelial cells (HUVECs) were used as a nonmyeloid comparison. AdTRAMdn inhibited LPS-induced signaling in SFs and HUVECs, reducing NF-kappaB activation and cytokine production, but did not inhibit LPS signaling in M-CSF derived human macrophages. Further investigation of other TLR ligands showed that AdTRAMdn was also able to inhibit signaling initiated by lipoteichoic acid, a TLR2 ligand, in SFs and HUVECs and lipoteichoic acid and macrophage-activating lipopeptide 2 signaling was also inhibited in TRAM(-/-) murine embryonic fibroblasts. We conclude that TRAM is an adaptor protein for both TLR4 and TLR2/6 signaling in SFs, HUVECs, and murine embryonic fibroblasts, but cannot demonstrate a role in human macrophages. PMID- 17277120 TI - Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. AB - Thymus-derived, naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells (nTregs) and Tregs induced in the periphery (iTregs) have both been implicated in regulating immune responses. However, the relationship between these populations in the same host, and their relative contribution to the overall Treg pool, has not been examined. Using a tumor-induced T cell tolerance model, we find that expansion of nTregs and de novo generation of iTregs both contribute to tumor specific T cell tolerance. In this system in which the number of tumor-specific nTregs can be controlled, the efficiency of nTreg expansion significantly exceeds that of the induction of Tregs from uncommitted progenitors in the tumor-bearing host. However, pre-existing nTregs are neither required for the induction of Tregs nor measurably impact on the extent of their accumulation. Instead, induction of Ag-specific regulatory cells from naive cells is intrinsically influenced by the tumor microenvironment and the presence of tumor Ag. PMID- 17277121 TI - A role for mammalian target of rapamycin in regulating T cell activation versus anergy. AB - Whether TCR engagement leads to activation or tolerance is determined by the concomitant delivery of multiple accessory signals, cytokines, and environmental cues. In this study, we demonstrate that the mammalian target of rapamycin (mTOR) integrates these signals and determines the outcome of TCR engagement with regard to activation or anergy. In vitro, Ag recognition in the setting of mTOR activation leads to full immune responses, whereas recognition in the setting of mTOR inhibition results in anergy. Full T cell activation is associated with an increase in the phosphorylation of the downstream mTOR target S6 kinase 1 at Thr(421)/Ser(424) and an increase in the mTOR-dependent cell surface expression of transferrin receptor (CD71). Alternatively, the induction of anergy results in markedly less S6 kinase 1 Thr(421)/Ser(424) phosphorylation and CD71 surface expression. Likewise, the reversal of anergy is associated not with proliferation, but rather the specific activation of mTOR. Importantly, T cells engineered to express a rapamycin-resistant mTOR construct are resistant to anergy induction caused by rapamycin. In vivo, mTOR inhibition promotes T cell anergy under conditions that would normally induce priming. Furthermore, by examining CD71 surface expression, we are able to distinguish and differentially isolate anergic and activated T cells in vivo. Overall, our data suggest that by integrating environmental cues, mTOR plays a central role in determining the outcome of Ag recognition. PMID- 17277122 TI - Bacterial c-di-GMP is an immunostimulatory molecule. AB - Cyclic diguanylate (c-di-GMP) is a bacterial intracellular signaling molecule. We have shown that treatment with exogenous c-di-GMP inhibits Staphylococcus aureus infection in a mouse model. We now report that c-di-GMP is an immodulator and immunostimulatory molecule. Intramammary treatment of mice with c-di-GMP 12 and 6 h before S. aureus challenge gave a protective effect and a 10,000-fold reduction in CFUs in tissues (p < 0.001). Intramuscular vaccination of mice with c-di-GMP coinjected with S. aureus clumping factor A (ClfA) Ag produced serum with significantly higher anti-ClfA IgG Ab titers (p < 0.001) compared with ClfA alone. Intraperitoneal injection of mice with c-di-GMP activated monocyte and granulocyte recruitment. Human immature dendritic cells (DCs) cultured in the presence of c-di-GMP showed increased expression of costimulatory molecules CD80/CD86 and maturation marker CD83, increased MHC class II and cytokines and chemokines such as IL-12, IFN-gamma, IL-8, MCP-1, IFN-gamma-inducible protein 10, and RANTES, and altered expression of chemokine receptors including CCR1, CCR7, and CXCR4. c-di-GMP-matured DCs demonstrated enhanced T cell stimulatory activity. c-di-GMP activated p38 MAPK in human DCs and ERK phosphorylation in human macrophages. c-di-GMP is stable in human serum. We propose that cyclic dinucleotides like c-di-GMP can be used clinically in humans and animals as an immunomodulator, immune enhancer, immunotherapeutic, immunoprophylactic, or vaccine adjuvant. PMID- 17277124 TI - AID-/-mus-/- mice are agammaglobulinemic and fail to maintain B220-CD138+ plasma cells. AB - The terminal stage of B cell differentiation culminates in the formation of plasma cells (PC), which secrete large quantities of Igs. Despite recent progress in understanding the molecular aspect of PC differentiation and maintenance, the requirement for the synthesis of secretory Igs as a contributing factor has not been explored. To address this issue, we generated activation-induced cytidine deaminase (AID)/secretory mu-chain (mus) double-knockout mice, in which a normally diverse repertoire of B cell receptors is retained, yet B cells are unable to synthesize secretory Igs. These mice possess polyclonal B cells but have no serum Igs. Following immunization in vivo, PCs, identified by CD138 expression and loss of the B220 marker, were starkly reduced in number in spleen and bone marrow of AID(-/-)mus(-/-) agammaglobulinemic mice compared with wild type mice. Upon mitogenic stimulation in vitro, AID(-/-)mus(-/-) B cells differentiated into plasmablasts to some extent, but showed reduced survival compared with wild-type B cells. We found no evidence that this reduced survival was attributable to accumulation of membrane IgM. Our results indicate that the synthesis of secretory Igs is a requirement for maintenance of B220(-)CD138(+) PCs. PMID- 17277123 TI - TLR signaling fine-tunes anti-influenza B cell responses without regulating effector T cell responses. AB - Influenza is a ssRNA virus that has been responsible for widespread morbidity and mortality; however, the innate immunological mechanisms that drive the adaptive anti-influenza immune response in vivo are yet to be fully elucidated. TLRs are pattern recognition receptors that bind evolutionarily conserved pathogen associated molecular patterns, induce dendritic cell maturation, and consequently aid the development of effective immune responses. We have examined the role of TLRs in driving effective T and B cell responses against influenza virus. We found TLR3 and its associated adapter molecule, Toll/IL-R domain-containing adaptor-inducing IFN-beta, did not play a role in the development of CD4(+) or CD8(+) T cell responses against influenza virus, nor did they influence influenza specific B cell responses. Surprisingly, TLR7 and MyD88 also played negligible roles in T cell activation and effector function upon infection with influenza virus; however, their signaling was critical for regulating anti-influenza B cell Ab isotype switching. The induction of appropriate anti-influenza humoral responses involved stimulation of TLRs on B cells directly and TLR-induced production of IFN-alpha, which acted to reduce IgG1 and increase IgG2a/c class switching. Notably, direct TLR signaling on B cells or T cell help through the CD40-CD40L interaction was sufficient to support B cell proliferation and IgG1 production, whereas IFN-alpha was critical for fine-tuning the nature of the isotype switch. Taken together, these data reveal that TLR signaling is not required for anti-influenza T cell responses, but through both direct and indirect means orchestrates appropriate anti-influenza B cell responses. PMID- 17277125 TI - Suppression of the effector phase of inflammatory arthritis by double-stranded RNA is mediated by type I IFNs. AB - Innate immune receptors that recognize nucleic acids, such as TLRs and RNA helicases, are potent activators of innate immunity that have been implicated in the induction and exacerbation of autoimmunity and inflammatory arthritis. Polyriboinosine-polyribocytidylic acid sodium salt (poly(IC)) is a mimic of dsRNA and viral infection that activates TLR3 and the RNA helicases retinoic acid induced gene-1 and melanoma differentiation-associated gene-5, and strongly induces type I IFN production. We analyzed the effects of systemic delivery of poly(IC) on the inflammatory effector phase of arthritis using the collagen Ab induced and KRN TCR-transgenic mouse serum-induced models of immune complex mediated experimental arthritis. Surprisingly, poly(IC) suppressed arthritis, and suppression was dependent on type I IFNs that inhibited synovial cell proliferation and inflammatory cytokine production. Administration of exogenous type I IFNs was sufficient to suppress arthritis. These results suggest a regulatory role for innate immune receptors for dsRNA in modulating inflammatory arthritis and provide additional support for an anti-inflammatory function of type I IFNs in arthritis that directly contrasts with a pathogenic role in promoting autoimmunity in systemic lupus. PMID- 17277126 TI - Peripheral tolerance induction using ethylenecarbodiimide-fixed APCs uses both direct and indirect mechanisms of antigen presentation for prevention of experimental autoimmune encephalomyelitis. AB - MHC class II (MHC II)-restricted T cell responses are a common driving force of autoimmune disease. Accordingly, numerous therapeutic strategies target CD4(+) T cells with the hope of attenuating autoimmune responses and restoring self tolerance. We have previously reported that i.v. treatment with Ag-pulsed, ethylenecarbodiimide (ECDI)-fixed splenocytes (Ag-SPs) is an efficient protocol to induce Ag-specific tolerance for prevention and treatment of experimental autoimmune encephalomyelitis (EAE). Ag-SPs coupled with peptide can directly present peptide:MHC II complexes to target CD4(+) T cells in the absence of costimulation to induce anergy. However, Ag-SPs coupled with whole protein also efficiently attenuates Ag-specific T cell responses suggesting the potential contribution of alternative indirect mechanisms/interactions between the Ag-SPs and target CD4(+) T cells. Thus, we investigated whether MHC II compatibility was essential to the underlying mechanisms by which Ag-SP induces tolerance during autoimmune disease. Using MHC-deficient, allogeneic, and/or syngeneic donor Ag SPs, we show that MHC compatibility between the Ag-SP donor and the host is not required for tolerance induction. Interestingly, we found that ECDI treatment induces apoptosis of the donor cell population which promotes uptake and reprocessing of donor cell peptides by host APCs resulting in the apparent MHC II independent induction of tolerance. However, syngeneic donor cells are more efficient at inducing tolerance, suggesting that Ag-SPs induce functional Ag-SP tolerance via both direct and indirect (cross-tolerance) mechanisms leading to prevention and effective treatment of autoimmune disease. PMID- 17277127 TI - Abrogation of antibody-mediated allograft rejection by regulatory CD4 T cells with indirect allospecificity. AB - Alloantibody is an important effector mechanism for allograft rejection. In this study, we tested the hypothesis that regulatory T cells with indirect allospecificity can prevent humoral rejection by using a rat transplant model in which acute rejection of MHC class I-disparate PVG.R8 heart grafts by PVG.RT1(u) recipients is mediated by alloantibody and is dependent upon help from CD4 T cells that can recognize the disparate MHC alloantigen only via the indirect pathway. Pretransplant treatment of PVG.RT1(u) recipients with anti-CD4 mAb plus donor-specific transfusion abrogated alloantibody production and prolonged PVG.R8 graft survival indefinitely. Naive syngeneic splenocytes injected into tolerant animals did not effect heart graft rejection, suggesting the presence of regulatory mechanisms. Adoptive transfer experiments into CD4 T cell reconstituted, congenitally athymic recipients confirmed that regulation was mediated by CD4 T cells and was alloantigen-specific. CD4 T cell regulation could be broken in tolerant animals either by immunizing with an immunodominant linear allopeptide or by depleting tolerant CD4 T cells, but surprisingly this resulted in neither alloantibody generation nor graft rejection. These findings demonstrate that anti-CD4 plus donor-specific transfusion treatment results in the development of CD4 regulatory T cells that recognize alloantigens via the indirect pathway and act in an Ag-specific manner to prevent alloantibody mediated rejection. Their development is associated with intrinsic tolerance within the alloantigen-specific B cell compartment that persists after T cell help is made available. PMID- 17277128 TI - The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. AB - IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor complex R1 subunits that are preferentially expressed on cells of epithelial origin; thus, we henceforth refer to them as the IL-20 subfamily cytokines. In this study, we show that primary human keratinocytes (KCs) express receptors for these cytokines and that IL-19, IL-20, IL-22, and IL-24 induce acanthosis in reconstituted human epidermis (RHE) in a dose-dependent manner. These cytokines also induce expression of the psoriasis-associated protein S100A7 and keratin 16 in RHE and cause persistent activation of Stat3 with nuclear localization. IL-22 had the most pronounced effects on KC proliferation and on the differentiation of KCs in RHE, inducing a decrease in the granular cell layer (hypogranulosis). Furthermore, gene expression analysis performed on cultured RHE treated with these cytokines showed that IL-19, IL-20, IL-22, and IL-24 regulate many of these same genes to variable degrees, inducing a gene expression profile consistent with inflammatory responses, wound healing re-epithelialization, and altered differentiation. Many of these genes have also been found to be up-regulated in psoriatic skin, including several chemokines, beta-defensins, S100 family proteins, and kallikreins. These results confirm that IL-20 subfamily cytokines are important regulators of epidermal KC biology with potentially pivotal roles in the immunopathology of psoriasis. PMID- 17277129 TI - The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. AB - Endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) is involved in the final processing of endogenous peptides presented by MHC class I molecules to CTLs. We generated ERAP1-deficient mice and analyzed cytotoxic responses upon infection with three viruses, including lymphocytic choriomeningitis virus, which causes vigorous T cell activation and is controlled by CTLs. Despite pronounced effects on the presentation of selected epitopes, the in vivo cytotoxic response was altered for only one of several epitopes tested. Moreover, control of lymphocytic choriomeningitis virus was not impaired in the knockout mice. Thus, we conclude that lack of ERAP1 has little influence on antiviral immunohierarchies and antiviral immunity in the infections studied. We also focused on the role of ERAP1 in cross-presentation. We demonstrate that ERAP1 is required for efficient cross-presentation of cell-associated Ag and of OVA/anti OVA immunocomplexes. Surprisingly, however, ERAP1 deficiency has no effect on cross-presentation of soluble OVA, suggesting that for soluble exogenous proteins, final processing may not take place in an environment containing active ERAP1. PMID- 17277130 TI - Epitope-dependent effect of anti-murine TIM-1 monoclonal antibodies on T cell activity and lung immune responses. AB - The TAPR locus containing the TIM gene family is implicated in the development of atopic inflammation in mouse, and TIM-1 allelic variation has been associated with the incidence of atopy in human patient populations. In this study, we show that manipulation of the TIM-1 pathway influences airway inflammation and pathology. Anti-TIM-1 mAbs recognizing distinct epitopes differentially modulated OVA-induced lung inflammation in the mouse. The epitopes recognized by these Abs were mapped, revealing that mAbs to both the IgV and stalk domains of TIM-1 have therapeutic activity. Unexpectedly, mAbs recognizing unique epitopes spanning exon 4 of the mucin/stalk domains exacerbated immune responses. Using Ag recall response studies, we demonstrate that the TIM-1 pathway acts primarily by modulating the production of T(H)2 cytokines. Furthermore, ex vivo cellular experiments indicate that TIM-1 activity controls CD4(+) T cell activity. These studies validate the genetic hypothesis that the TIM-1 locus is linked to the development of atopic disease and suggest novel therapeutic strategies for targeting asthma and other atopic disorders. PMID- 17277131 TI - Dendritic cells sensitize TCRs through self-MHC-mediated Src family kinase activation. AB - It is unclear whether peptide-MHC class II (pMHC) complexes on distinct types of APCs differ in their capacity to trigger TCRs. In this study, we show that individual cognate pMHC complexes displayed by dendritic cells (DCs), as compared with nonprofessional APCs, are far better in productively triggering Ag-specific TCRs independently of conventional costimulation. As we further show, this is accomplished by the unique ability of DCs to robustly activate the Src family kinases (SFKs) Lck and Fyn in T cells even in the absence of cognate peptide. Instead, this form of SFK activation depends on interactions of DC-displayed MHC with TCRs of appropriate restriction, suggesting a central role of self-pMHC recognition. DC-mediated SFK activation leads to "TCR licensing," a process that dramatically increases sensitivity and magnitude of the TCR response to cognate pMHC. Thus, TCR licensing, besides costimulation, is a main mechanism of DCs to present Ag effectively. PMID- 17277132 TI - TNF receptor-associated factor 2-dependent canonical pathway is crucial for the development of Peyer's patches. AB - Activation of the noncanonical pathway through the interaction of lymphotoxin (LT)-alpha(1)beta(2) and LT-betaR is essential for the development of secondary lymphoid organs including lymph nodes (LN) and Peyer's patches (PP). Although TNFR-associated factor (TRAF) 2 and TRAF5 were identified as signal transducers for the LT-betaR, roles for TRAF2 and TRAF5 in the development of secondary lymphoid organs remain obscure. In this study, we show that PP but not mesenteric LN development is severely impaired in traf2(-/-) and traf2(-/-)traf5(-/-) mice. Development of VCAM-1(+) and ICAM-1(+) mesenchymal cells and expression of CXCL13, a crucial chemokine for the development of PP, are severely impaired in PP anlagen in the intestines of traf2(-/-) mice. Surprisingly, TNF-alpha stimulation potently up-regulates cxcl13 mRNA expression in wild-type murine embryonic fibroblasts, which is impaired in traf2(-/-) and relA(-/-) murine embryonic fibroblasts. Moreover, RelA is recruited to the promoter of cxcl13 gene upon TNF-alpha stimulation and PP development is impaired in TNFR type 1 (tnfr1)( /-) mice. These results underscore a crucial role for the TNFR1-TRAF2-RelA dependent canonical pathway in the development of PP through up-regulation of cxcl13 mRNA. PMID- 17277133 TI - CXC chemokine ligand 9/monokine induced by IFN-gamma production by tumor cells is critical for T cell-mediated suppression of cutaneous tumors. AB - The role of tumor-produced chemokines in the growth of malignancies remains poorly understood. We retrieved an in vivo growing MCA205 fibrosarcoma and isolated tumor cell clones that produce both CXCL9/monokine induced by IFN-gamma (Mig) and CXCL10/IFN-gamma-inducible protein 10 following stimulation with IFN gamma and clones that produce IFN-gamma-inducible protein 10 but not Mig. The Mig deficient variants grew more aggressively as cutaneous tumors in wild-type mice than the Mig-producing tumor cells. The growth of Mig-expressing, but not Mig deficient, tumor cells was suppressed by NK and T cell activity. Transduction of Mig-negative variants to generate constitutive tumor cell production of Mig resulted in T cell-dependent rejection of the tumors and in induction of protective tumor-specific CD8(+) T cell responses to Mig-deficient tumors. The results indicate a critical role for tumor-derived Mig in T cell-mediated responses to cutaneous fibrosarcomas and suggest the loss of Mig expression as a mechanism used by tumor cells to evade these responses. PMID- 17277134 TI - Fas receptor clustering and involvement of the death receptor pathway in rituximab-mediated apoptosis with concomitant sensitization of lymphoma B cells to fas-induced apoptosis. AB - Ab binding to CD20 has been shown to induce apoptosis in B cells. In this study, we demonstrate that rituximab sensitizes lymphoma B cells to Fas-induced apoptosis in a caspase-8-dependent manner. To elucidate the mechanism by which Rituximab affects Fas-mediated cell death, we investigated rituximab-induced signaling and apoptosis pathways. Rituximab-induced apoptosis involved the death receptor pathway and proceeded in a caspase-8-dependent manner. Ectopic overexpression of FLIP (the physiological inhibitor of the death receptor pathway) or application of zIETD-fmk (specific inhibitor of caspase-8, the initiator-caspase of the death receptor pathway) both specifically reduced rituximab-induced apoptosis in Ramos B cells. Blocking the death receptor ligands Fas ligand or TRAIL, using neutralizing Abs, did not inhibit apoptosis, implying that a direct death receptor/ligand interaction is not involved in CD20-mediated cell death. Instead, we hypothesized that rituximab-induced apoptosis involves membrane clustering of Fas molecules that leads to formation of the death inducing signaling complex (DISC) and downstream activation of the death receptor pathway. Indeed, Fas coimmune precipitation experiments showed that, upon CD20 cross-linking, Fas-associated death domain protein (FADD) and caspase-8 were recruited into the DISC. Additionally, rituximab induced CD20 and Fas translocation to raft-like domains on the cell surface. Further analysis revealed that, upon stimulation with rituximab, Fas, caspase-8, and FADD were found in sucrose-gradient raft fractions together with CD20. In conclusion, in this study, we present evidence for the involvement of the death receptor pathway in rituximab-induced apoptosis of Ramos B cells with concomitant sensitization of these cells to Fas-mediated apoptosis via Fas multimerization and recruitment of caspase-8 and FADD to the DISC. PMID- 17277135 TI - p21CIP1/WAF1 controls proliferation of activated/memory T cells and affects homeostasis and memory T cell responses. AB - Development of autoantibodies and lupus-like autoimmunity by 129/Sv x C57BL/6 p21(-/-) mice has established that cell cycle deregulation is one the defective pathways leading to break of tolerance. Memory T cell accumulation is thought to be related to tolerance loss in murine lupus models. We studied T cell memory responses in C57BL/6 p21(-/-) mice that develop lupus-like disease manifestations. p21 did not affect primary proliferation of naive T cells, and was required for cycling control, but not for apoptosis of activated/memory T cells. When we induced apoptosis by secondary TCR challenge, surviving memory T cells depended on p21 for proliferation control. Under conditions of secondary T cell stimulation that did not cause apoptosis, p21 was also needed for regulation of activated/memory T cell expansion. The requirement for p21 in the control of T cell proliferation of activated/memory T cells suggests that in addition to apoptosis, cycling regulation by p21 constitutes a new pathway for T cell homeostasis. Concurring with this view, we found accumulation in p21(-/-) mice of memory CD4(+) T cells that showed increased proliferative potential after TCR stimulation. Furthermore, OVA immunization of p21(-/-) mice generated hyperresponsive OVA-specific T cells. Overall, the data show that p21 controls the proliferation of only activated/memory T cells, and suggest that p21 forms part of the memory T cell homeostasis mechanism, contributing to maintenance of tolerance. PMID- 17277136 TI - A novel postpriming regulatory check point of effector/memory T cells dictated through antigen density threshold-dependent anergy. AB - CTLs act as the effector arm of the cell-mediated immune system to kill undesirable cells. Two processes regulate these effector cells to prevent self reactivity: a thymic selection process that eliminates autoreactive clones and a multistage activation or priming process that endows them with a license to kill cognate target cells. Hitherto no subsequent regulatory restrictions have been ascribed for properly primed and activated CTLs that are licensed to kill. In this study we show that CTLs possess a novel postpriming regulatory mechanism(s) that influences the outcome of their encounter with cognate target cells. This mechanism gauges the degree of Ag density, whereupon reaching a certain threshold significant changes occur that induce anergy in the effector T cells. The biological consequences of this Ag-induced postpriming control includes alterations in the expression of cell surface molecules that control immunological synapse activity and cytokine profiles and induce retarded cell proliferation. Most profound is genome-wide microarray analysis that demonstrates changes in the expression of genes related to membrane potential, TCR signal transduction, energy metabolism, and cell cycle control. Thus, a discernible and unique gene expression signature for anergy as a response to high Ag density has been observed. Consequently, activated T cells possess properties of a self referential sensory organ. These studies identify a new postpriming control mechanism of CTL with anergenic-like properties. This mechanism extends our understanding of the control of immune function and regulation such as peripheral tolerance, viral infections, antitumor immune responses, hypersensitivity, and autoimmunity. PMID- 17277137 TI - Phenotypic and functional analysis of immune CD8+ T cell responses induced by a single injection of a HIV DNA vaccine in mice. AB - HIV DNA vaccines are potent inducers of cell-mediated immune (CMI) response in mice but elicit poor HIV-specific IFN-gamma-producing T cells in monkeys and humans. In this study, we performed kinetic analyses on splenocytes of BALB/c mice that were immunized by a single injection with a unique DNA vaccine. Using IFN-gamma-ELISPOT and multiparametric FACS analysis, we characterized the induced CMI response. We found that the response was detectable for at least 63 wk. ELISPOT detection of IFN-gamma-producing T cells showed a profile with two waves separated by a long period of minimal response. Multiparametric FACS analysis showed two populations of CD3(+)CD8(+) T cells that were specific for all HIV Ags. These cells had similar robust proliferation abilities and contained granzyme B. However, only a few produced IFN-gamma. Both IFN-gamma-producing and non-IFN-gamma-producing HIV-specific CD8(+) T cells were detected in the early stage (week (W)1 and W2 postimmunization (PI)), in the prolonged intermediate period of minimal response (W4-W26 PI), and in the final late phase of increased response (W30-W63 PI). Our longitudinal characterization showed that both subsets of cells underwent expansion, contraction, and memory generation/maintenance phases throughout the lifespan of the animal. Altogether, these findings bring insight to the heterogeneity of the immune T cell response induced by a single immunization with this DNA and strengthen the concept that used of the IFN-gamma ELISPOT assay alone may be insufficient to detect critical T cell responses to candidate HIV vaccines. PMID- 17277138 TI - Requirement for phosphoinositide 3-kinase p110delta signaling in B cell antigen receptor-mediated antigen presentation. AB - The BCR serves to both signal cellular activation and enhance uptake and presentation of Ags by B cells; however, the intracellular signaling mechanisms linking the BCR to Ag presentation functions have been controversial. PI3Ks are critical signaling enzymes controlling many cellular processes, with the p110delta isoform playing a critical role in BCR signaling. In this study, we used pharmacological and genetic approaches to evaluate the role of p110delta signaling in Ag presentation by primary B lymphocytes. It was found that activation of allogeneic T cells is significantly reduced when B cells are pretreated with global PI3K inhibitors, but was intact when p110delta signaling was specifically inactivated. In contrast, inactivation of p110delta significantly impaired the ability of B cells to activate T cells in a BCR mediated Ag uptake and presentation model. Prestimulation of p110delta inactivated B cells with anti-CD40 or LPS could not rescue their BCR-mediated Ag presentation ability to normal levels. p110delta signaling was required for efficient presentation of either anti-Ig or protein Ag via a lysozyme-specific BCR. p110delta-inactivated B cells were able to internalize Ag normally, and no defects in association of Ag with lysosome-associated membrane protein 1(+) late endosomes were observed; however, these cells were less effective in forming polarized conjugates with Ag-specific T cells. Our data demonstrate a role for p110delta signaling in B cell Ag presentation function, implicating 3 phosphoinositides and their targets in the latter stages of this process. PMID- 17277139 TI - The N terminus of the non-T cell activation linker (NTAL) confers inhibitory effects on pre-B cell differentiation. AB - SLP-65 and the linker for activation of T cells (LAT) are central adaptor proteins that link the activated pre-BCR to downstream events in pre-B cells. Recently, a new transmembrane adaptor called NTAL/LAB/LAT2 (hereafter called NTAL for non-T cell activation linker) with striking functional and structural similarity to LAT has been identified in B cells. In this study, we compare the function of NTAL and LAT in pre-BCR signaling and show that, in contrast to LAT, NTAL does not induce pre-BCR down-regulation, calcium flux, or pre-B cell differentiation. To test whether differences between NTAL-mediated and LAT mediated signaling are caused by the missing phospholipase C (PLC)-gamma binding motif in NTAL, we inserted the PLC-gamma1/2 binding motif of LAT into NTAL. This insertion rendered NTAL capable of activating pre-BCR down-regulation and calcium flux. Unexpectedly however, the ability of NTAL to induce calcium flux was not sufficient to promote pre-B cell differentiation, suggesting that the PLC-gamma binding motif has only partial effects on NTAL-mediated pre-BCR signaling. By generating chimeric swap mutants, we identified the N terminus of NTAL as an inhibitory domain that prevents pre-B cell differentiation while allowing pre-BCR down-regulation and receptor-mediated calcium flux. Our data suggest that, in addition to the missing PLC-gamma1/2 binding motif, the N terminus is responsible for the functional differences between NTAL and LAT in pre-B cells. PMID- 17277140 TI - The arthritis severity quantitative trait loci Cia4 and Cia6 regulate neutrophil migration into inflammatory sites and levels of TNF-alpha and nitric oxide. AB - Neutrophils are required for the development of arthritis, and their migration into the synovial tissue coincides with the onset of clinical disease. Synovial neutrophil numbers also correlate with rheumatoid arthritis disease activity and severity. We hypothesized that certain arthritis severity genes regulate disease via the regulation of neutrophil migration into the joint. This hypothesis was tested in the synovial-like air pouch model injected with carrageenan using arthritis-susceptible DA and arthritis-resistant F344 rats. DA had nearly 3-fold higher numbers of exudate neutrophils compared with F344 (p < 0.001). Five DA.F344(QTL) strains congenic for severity loci and protected from autoimmune arthritis were studied. Only DA.F344(Cia4) (chromosome 7) and DA.F344(Cia6) (chromosome 8) congenics had significantly lower exudate neutrophil counts compared with DA. TNF-alpha levels were 2.5-fold higher in DA exudates as compared with F344 exudates, and that difference was accounted for by the Cia4 locus. Exudate levels of NO, a known inhibitor of neutrophil chemotaxis, were higher in F344, compared with DA, and that difference was accounted for by Cia6. This is the first time that non-MHC autoimmune arthritis loci are found to regulate three central components of the innate immune response implicated in disease pathogenesis, namely neutrophil migration into an inflammatory site, as well as exudate levels of TNF-alpha and NO. These observations underscore the importance of identifying the Cia4 and Cia6 genes, and suggest that they should generate useful novel targets for development of new therapies. PMID- 17277141 TI - Genetic dissection of spontaneous autoimmunity driven by 129-derived chromosome 1 Loci when expressed on C57BL/6 mice. AB - Extensive evidence indicates that genetic predisposition is a central element in susceptibility to systemic lupus erythematosus both in humans and animals. We have previously shown that a congenic line carrying a 129-derived chromosome 1 interval on the C57BL/6 background developed humoral autoimmunity. To further dissect the contribution to autoimmunity of this 129 interval, we have created six subcongenic strains carrying fractions of the original 129 region and analyzed their serological and cellular phenotypes. At 1 year of age the congenic strain carrying a 129 interval between the microsatellites D1Mit15 (87.9 cM) and D1Mit115 (99.7 cM) (B6.129chr1b) had high levels of autoantibodies, while all the other congenic lines were not significantly different from the C57BL/6 controls. The B6.129chr1b strain displayed only mild proliferative glomerulonephritis despite high levels of IgG and C3 deposited in the kidneys. FACS analysis of the spleens revealed that the B6.129chr1b mice had a marked increase in the percentage of activated T cells associated with a significant reduction in the proportion of CD4(+)CD25(high) regulatory T cells. Moreover, this analysis showed a significantly reduced percentage of marginal zone B cells that preceded autoantibody production. Interestingly the 129chr1b-expressing bone marrow derived macrophages displayed an impaired uptake of apoptotic cells in vitro. Collectively, our data indicate that the 129chr1b segment when recombined on the C57BL/6 genomic background is sufficient to induce loss of tolerance to nuclear Ags. These findings have important implication for the interpretation of the autoimmune phenotype associated with gene-targeted models. PMID- 17277142 TI - Insect baculoviruses strongly potentiate adaptive immune responses by inducing type I IFN. AB - Baculoviruses (BVs) are dsDNA viruses that are pathogenic for insects. They have been used worldwide as selective bioinsecticides and for producing recombinant proteins in insect cells. Surprisingly, despite their widespread use in research and industry and their dissemination in the environment, the potential effects of these insect viruses on the immune responses of mammals remain totally unknown. We show in this study that BVs have strong adjuvant properties in mice, promoting potent humoral and CD8(+) T cell adaptive responses against coadministered Ag. BVs also induce the in vivo maturation of dendritic cells and the production of inflammatory cytokines. We demonstrate that BVs play a major role in the strong immunogenicity of virus-like particles produced in the BV-insect cell expression system. The presence of even small numbers of BVs among the recombinant proteins produced in the BV expression system may therefore strengthen the immunological properties of these proteins. This adjuvant behavior of BVs is mediated primarily by IFN-alphabeta, although mechanisms independent of type I IFN signaling are also involved. This study demonstrates that nonpathogenic insect viruses may have a strong effect on the mammalian immune system. PMID- 17277143 TI - Mucosal HIV-1 pox virus prime-boost immunization induces high-avidity CD8+ T cells with regime-dependent cytokine/granzyme B profiles. AB - The quality of virus-specific CD8(+) CTL immune responses generated by mucosal and systemic poxvirus prime-boost vaccines were evaluated in terms of T cell avidity and single-cell analysis of effector gene expression. Intranasal (I.N.) immunization regimes generated higher avidity CTL responses specific for HIV K(d)Gag(197-205) (amino acid sequence AMQMLKETI; H-2K(d) binding) compared with i.m. immunization regime. Single-cell RT-PCR of K(d)Gag(197-205)-specific mucosal and systemic CTL revealed that the cytokine and granzyme B expression profiles were dependent on both the route and time after immunization. The I.N./i.m. immunized group elicited elevated number of CTL-expressing granzyme B mRNA from the genitomucosal sites compared with the i.m./i.m. regime. Interestingly, CTL generated after both I.N. or i.m. immunization demonstrated expression of Th2 cytokine IL-4 mRNA that was constitutively expressed over time, although lower numbers were observed after I.N./I.N. immunization. Results suggest that after immunization, Ag-specific CTL expression of IL-4 may be an inherent property of the highly evolved poxvirus vectors. Current observations indicate that the quality of CTL immunity generated after immunization can be influenced by the inherent property of vaccine vectors and route of vaccine delivery. A greater understanding of these factors will be crucial for the development of effective vaccines in the future. PMID- 17277144 TI - RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. AB - RICK is a kinase that has been implicated in Nod1 and Nod2 signaling. In addition, RICK has been proposed to mediate TLR signaling in that its absence confers reduced responses to certain bacterial products such as LPS. We show here that macrophages and mice lacking RICK are defective in their responses to Nod1 and Nod2 agonists but exhibit unimpaired responses to synthetic and highly purified TLR agonists. Furthermore, production of chemokines induced by the bacterial dipeptide gamma-d-glutamyl-meso-diaminopimelic acid was intact in MyD88 deficient mice but abolished in RICK-null mice. Stimulation of macrophages with muramyl dipeptide, the Nod2 activator, enhanced immune responses induced by LPS, IFN-gamma, and heat-killed Listeria in wild-type but not in RICK- or Nod2 deficient macrophages. Finally, we show that the absence of RICK or double deficiency of Nod1 and Nod2 was associated with reduced cytokine production in Listeria-infected macrophages. These results demonstrate that RICK functions in innate immunity by mediating Nod1 and Nod2 signaling but not TLR-mediated immune responses. PMID- 17277145 TI - Mucosal luminal manipulation of T cell geography switches on protective efficacy by otherwise ineffective parenteral genetic immunization. AB - Genetic immunization holds great promise for future vaccination against mucosal infectious diseases. However, parenteral genetic immunization is ineffective in control of mucosal intracellular infections, and the underlying mechanisms have remained unclear. By using a model of parenteral i.m. genetic immunization and pulmonary tuberculosis (TB), we have investigated the mechanisms that determine the failure and success of parenteral genetic immunization. We found that lack of protection from pulmonary Mycobacterium tuberculosis (M.tb) challenge by i.m. immunization with a recombinant adenovirus-vectored tuberculosis vaccine was linked to the absence of M.tb Ag-specific T cells within the airway lumen before M.tb challenge despite potent T cell activation in the systemic compartments. Furthermore, pulmonary mycobacterial challenge failed to recruit CD8 T cells into the airway lumen of i.m. immunized mice. Such defect in T cell recruitment, intra airway CTL, and immune protection was restored by creating acute inflammation in the airway with inflammatory agonists such as virus. However, the Ag-specific T cells recruited as such were not retained in the airway lumen, resulting in a loss of protection. In comparison, airway exposure to low doses of soluble M.tb Ags not only recruited but retained Ag-specific CD8 T cells in the airway lumen over time that provided robust protection against M.tb challenge. Thus, our study reveals that mucosal protection by parenteral immunization is critically determined by T cell geography, i.e., whether Ag-specific T cells are within or outside of the mucosal lumen and presents a feasible solution to empower parenteral immunization strategies against mucosal infectious diseases. PMID- 17277146 TI - Rapid clonal expansion and prolonged maintenance of memory CD8+ T cells of the effector (CD44highCD62Llow) and central (CD44highCD62Lhigh) phenotype by an archaeosome adjuvant independent of TLR2. AB - Vaccines capable of eliciting long-term T cell immunity are required for combating many diseases. Live vectors can be unsafe whereas subunit vaccines often lack potency. We previously reported induction of CD8(+) T cells to Ag entrapped in archaeal glycerolipid vesicles (archaeosomes). In this study, we evaluated the priming, phenotype, and functionality of the CD8(+) T cells induced after immunization of mice with OVA-Methanobrevibacter smithii archaeosomes (MS OVA). A single injection of MS-OVA evoked a profound primary response but the numbers of H-2K(b)OVA(257-264)-specific CD8(+) T cells declined by 14-21 days, and <1% of primarily central phenotype (CD44(high)CD62L(high)) cells persisted. A booster injection of MS-OVA at 3-11 wk promoted massive clonal expansion and a peak effector response of approximately 20% splenic/blood OVA(257-264)-specific CD8(+) T cells. Furthermore, contraction was protracted and the memory pool (IL 7Ralpha(high)) of approximately 5% included effector (CD44(high)CD62L(low)) and central (CD44(high)CD62L(high)) phenotype cells. Recall response was observed even at >300 days. CFSE-labeled naive OT-1 (OVA(257-264) TCR transgenic) cells transferred into MS-OVA-immunized recipients cycled profoundly (>90%) within the first week of immunization indicating potent Ag presentation. Moreover, approximately 25% cycling of Ag-specific cells was seen for >50 days, suggesting an Ag depot. In vivo, CD8(+) T cells evoked by MS-OVA killed >80% of specific targets, even at day 180. MS-OVA induced responses similar in magnitude to Listeria monocytogenes-OVA, a potent live vector. Furthermore, protective CD8(+) T cells were induced in TLR2-deficient mice, suggesting nonengagement of TLR2 by archaeal lipids. Thus, an archaeosome adjuvant vaccine represents an alternative to live vectors for inducing CD8(+) T cell memory. PMID- 17277147 TI - Expression of the p60 autolysin enhances NK cell activation and is required for listeria monocytogenes expansion in IFN-gamma-responsive mice. AB - Both peptidoglycan and muropeptides potently modulate inflammatory and innate immune responses. The secreted Listeria monocytogenes p60 autolysin digests peptidoglycan and promotes bacterial infection in vivo. Here, we report that p60 contributes to bacterial subversion of NK cell activation and innate IFN-gamma production. L. monocytogenes deficient for p60 (Deltap60) competed well for expansion in mice doubly deficient for IFNAR1 and IFN-gammaR1 or singly deficient for IFN-gammaR1, but not in wild-type, IFNAR1(-/-), or TLR2(-/-) mice. The restored competitiveness of p60-deficient bacteria suggested a specific role for p60 in bacterial subversion of IFN-gamma-mediated immune responses, since in vivo expansion of three other mutant L. monocytogenes strains (DeltaActA, DeltaNamA, and DeltaPlcB) was not complemented in IFN-gammaR1(-/-) mice. Bacterial expression of p60 was not required to induce socs1, socs3, and il10 expression in infected mouse bone marrow macrophages but did correlate with enhanced production of IL-6, IL-12p70, and most strikingly IFN-gamma. The primary source of p60 dependent innate IFN-gamma was NK cells, whereas bacterial p60 expression did not significantly alter innate IFN-gamma production by T cells. The mechanism for p60 dependent NK cell stimulation was also indirect, given that treatment with purified p60 protein failed to directly activate NK cells for IFN-gamma production. These data suggest that p60 may act on infected cells to indirectly enhance NK cell activation and increase innate IFN-gamma production, which presumably promotes early bacterial expansion through its immunoregulatory effects on bystander cells. Thus, the simultaneous induction of IFN-gamma production and factors that inhibit IFN-gamma signaling may be a common strategy for misdirection of early antibacterial immunity. PMID- 17277148 TI - TLR9 signaling in B cells determines class switch recombination to IgG2a. AB - Although IgG2a is the most potent Ab isotype in the host response to viral and bacterial infections, the regulation of class switch recombination to IgG2a in vivo is not yet well understood. Recognition of pathogen-associated molecular patterns by dendritic cells expressing TLRs, like TLR7, recognizing ssRNA, or TLR9, recognizing DNA rich in nonmethylated CG motifs (CpG), favors induction of Th1 responses. It is generally assumed that these Th1 responses are responsible for the TLR-mediated induction of IgG2a. Using virus-like particles loaded with CpGs, we show here that TLR9 ligands can directly stimulate B cells to undergo isotype switching to IgG2a. Unexpectedly, TLR9 expression in non-B cells did not affect isotype switching in the Ab response against virus-like particles. Thus, TLR9 can regulate isotype switching to IgG2a directly by interacting with B cells rather than indirectly by inducing Th1 responses. PMID- 17277149 TI - Heat shock protein 27 regulates neutrophil chemotaxis and exocytosis through two independent mechanisms. AB - The targets of the p38 MAPK pathway responsible for regulation of neutrophil chemotaxis and exocytosis are unknown. One target of this pathway is the actin binding protein, heat shock protein 27 (Hsp27). Therefore, we tested the hypothesis that Hsp27 mediates p38 MAPK-dependent chemotaxis and exocytosis in human neutrophils through regulation of actin reorganization. Sequestration of Hsp27 by introduction of anti-Hsp27 Ab, but not an isotype Ab, inhibited fMLP stimulated chemotaxis, increased cortical F-actin in the absence of fMLP stimulation, and inhibited fMLP-stimulated exocytosis. Pretreatment with latrunculin A prevented actin reorganization and the changes in fMLP-stimulated exocytosis induced by Hsp27 sequestration. To determine the role of Hsp27 phosphorylation, wild-type, phosphorylation-resistant, or phosphorylation mimicking recombinant Hsp27 was introduced into neutrophils by electroporation. The phosphorylation-resistant mutant significantly reduced migration toward fMLP, whereas none of the Hsp27 proteins affected fMLP-stimulated or TNF-alpha stimulated exocytosis or actin polymerization. Endogenous Hsp27 colocalized with F-actin in unstimulated and fMLP-stimulated neutrophils, whereas phosphorylated Hsp27 showed cytosolic localization in addition to colocalization with F-actin. Our results suggest that Hsp27 regulates neutrophil chemotaxis and exocytosis in an actin-dependent, phosphorylation-independent manner. Phosphorylation of Hsp27 regulates chemotaxis, but not exocytosis, independent of regulation of actin reorganization. PMID- 17277150 TI - Fas-associated death domain-containing protein-mediated antiviral innate immune signaling involves the regulation of Irf7. AB - The induction of type I (alphabeta) IFN following virus infection is necessary for the stimulation of effective antiviral host defense. In fibroblasts, a subset of primary genes (including those encoding IFN-beta and IFN-alpha4) are induced directly by intracellular dsRNA generated by the virus during its replication. These primary type I IFNs induce expression of IFN regulatory factor (IRF)-7, required for production of a second cascade of IFN-alpha subtypes and the further establishment of a complete antiviral state. Previously, we had reported on a role for Fas-associated death domain-containing protein (FADD) in the control of TLR-independent innate immune responses to virus infection. Our data in this study demonstrate that FADD is not only required for efficient primary gene induction, but is also essential for induction of Irf7 and effective expression of secondary IFN-alphas and other antiviral genes. Ectopic overexpression of IRF 7 partially rescued dsRNA responsiveness and IFN-alpha production, and a constitutively active variant of IRF-7 displayed normal activity in Fadd(-/-) murine embryonic fibroblasts. MC159, a FADD-interacting viral protein encoded by the molluscum contagiosum poxvirus was found to inhibit dsRNA-activated signaling events upstream of IRF-7. These data indicate that FADD's antiviral activity involves regulation of IRF-7-dependent production of IFN-alpha subtypes and consequent induction of secondary antiviral genes. PMID- 17277152 TI - Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. AB - Influenza virus-infected cells undergo apoptosis and become susceptible to phagocytosis by macrophages in vitro, and this leads to the propagation of the virus being inhibited. We previously showed that inhibitors of phagocytosis increased the rate of mortality among influenza virus-infected mice. However, the mode of the phagocytosis of influenza virus-infected cells in vivo has not been investigated. We, in this study, assessed this issue by histochemically analyzing bronchoalveolar lavage cells and lung tissue obtained from C57BL/6 mice infected with influenza A/WSN (H1N1) virus. Both neutrophils and macrophages accumulated in the lung soon after the viral challenge, and either type of cell was capable of phagocytosing influenza virus-infected, apoptotic cells. Changes in the level of phagocytosis and the amount of virus in lung tissue roughly correlated with each other. Furthermore, alveolar macrophages prepared from influenza virus infected mice showed greater phagocytic activity than those from uninfected mice. The phagocytic activity of macrophages was stimulated in vitro by a heat-labile substance(s) released from influenza virus-infected cells undergoing apoptosis. These results suggested that the level of phagocytosis is augmented both quantitatively and qualitatively in the lung of influenza virus-infected animals so that infected cells are effectively eliminated. Finally, lack of TLR4 caused an increase in the rate of mortality among influenza virus-challenged mice and a decrease in the level of phagocytosis of apoptotic cells in the lung. TLR4 could thus play an important role in the host defense against influenza by positively regulating the phagocytic elimination of infected cells. PMID- 17277151 TI - PU.1 redirects adenovirus to lysosomes in alveolar macrophages, uncoupling internalization from infection. AB - Adenovirus is endocytosed and efficiently destroyed by human and murine alveolar macrophages (AMs) and rapidly cleared from the lungs of wild-type but not GM-CSF( /-) mice. We hypothesized that GM-CSF may regulate adenovirus clearance in AMs via the transcription factor PU.1 by redirecting virion trafficking from the nucleus to lysosomes. This hypothesis was tested in murine AM cell lines with altered GM-CSF and/or PU.1 expression including MH-S (GM-CSF(+/+)PU.1(Pos)), mAM (GM-CSF(-/-)/PU.1(Neg)), and mAM(PU.1+) (GM-CSF(-/-)/PU.1(Pos); PU.1-transduced mAM cells) and A549 (an epithelial-like cell line) using a human adenovirus expressing a beta-galactosidase reporter. In PU.1(Neg) mAM and A549 cells, adenovirus efficiently escaped from endosomes, translocated to the nucleus, and expressed the viral reporter in most cells. In marked contrast, in PU.1(Pos) mAM(PU.1+) and MH-S cells, adenovirus failed to escape from endosomes, colocalized exclusively with endosome/lysosome markers (Rab5, Rab7, and Lamp1), and rarely expressed the reporter. Retroviral expression of PU.1 in A549 cells blocked endosomal escape, nuclear translocation and reporter expression. Inhibition of endosome acidification also blocked escape, nuclear translocation, and reporter expression in PU.1(Neg) cells. The effect of PU.1 on viral trafficking and transduction could not be explained by an effect on endosome acidification or on differences in viral load. PU.1 reduced expression of integrin beta(5), a host factor important for endosomal escape of adenovirus, suggesting that PU.1 redirects adenoviral trafficking by modulating integrin signaling. These results demonstrate that PU.1 uncouples infection from internalization in AMs, providing a mechanism for AMs to avoid infection by adenovirus during clearance. PMID- 17277153 TI - FTY720 ameliorates Th1-mediated colitis in mice by directly affecting the functional activity of CD4+CD25+ regulatory T cells. AB - Following the present concepts, the synthetic sphingosine analog of myriocin FTY720 alters migration and homing of lymphocytes via sphingosine 1-phosphate receptors. However, several studies indicate that the immunosuppressive properties of FTY720 may alternatively be due to tolerogenic activities via modulation of dendritic cell differentiation or based on direct effects on CD4(+)CD25(+) regulatory T cells (Treg). As Treg play an important role for the cure of inflammatory colitis, we used the Th1-mediated 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis model to address the therapeutic potential of FTY720 in vivo. A rectal enema of TNBS was given to BALB/c mice. FTY720 was administered i.p. from days 0 to 3 or 3 to 5. FTY720 substantially reduced all clinical, histopathologic, macroscopic, and microscopic parameters of colitis analyzed. The therapeutic effects of FTY720 were associated with a down-regulation of IL-12p70 and subsequent Th1 cytokines. Importantly, FTY720 treatment resulted in a prominent up-regulation of FoxP3, IL-10, TGFbeta, and CTLA4. Supporting the hypothesis that FTY720 directly affects functional activity of CD4(+)CD25(+) Treg, we measured a significant increase of CD25 and FoxP3 expression in isolated lamina propria CD4(+) T cells of FTY720-treated mice. The impact of FTY720 on Treg induction was further confirmed by concomitant in vivo blockade of CTLA4 or IL-10R which significantly abrogated its therapeutic activity. In conclusion, our data provide clear evidence that in addition to its well-established effects on migration FTY720 leads to a specific down-regulation of proinflammatory signals while simultaneously inducing functional activity of CD4(+)CD25(+) Treg. Thus, FTY720 may offer a promising new therapeutic strategy for the treatment of IBD. PMID- 17277154 TI - CD44 is a negative regulator of acute pulmonary inflammation and lipopolysaccharide-TLR signaling in mouse macrophages. AB - CD44 is a transmembrane adhesion molecule and hemopoietic CD44 has an essential role in hyaluronan clearance and resolution of noninfectious lung injury. In this study, we examined the role of CD44 in acute pulmonary inflammation and in the regulation of LPS-TLR signaling. Following intratracheally LPS treatment, CD44(-/ ) mice demonstrated an exaggerated inflammatory response characterized by increased inflammatory cell recruitment, elevated chemokine expression in bronchoalveolar lavage fluid, and a marked increase in NF-kappaB DNA-binding activity in lung tissue in vivo and in macrophages in vitro. Furthermore, CD44(-/ ) mice were more susceptible to LPS-induced shock. Reconstitution of hemopoietic CD44 reversed the inflammatory phenotype. We further found that the induction of the negative regulators of TLR signaling IL-1R-associated kinase-M, Toll interacting protein, and A20 by intratracheal LPS in vivo and in macrophages in vitro was significantly reduced in CD44(-/-) mice. Collectively, these data suggest CD44 plays a previously unrecognized role in preventing exaggerated inflammatory responses to LPS by promoting the expression of negative regulators of TLR-4 signaling. PMID- 17277155 TI - New animal model of shigellosis in the Guinea pig: its usefulness for protective efficacy studies. AB - It has been difficult to evaluate the protective efficacy of vaccine candidates against shigellosis, a major form of bacillary dysentery caused by Shigella spp. infection, because of the lack of suitable animal models. To develop a proper animal model representing human bacillary dysentery, guinea pigs were challenged with virulent Shigella flexneri serotype 2a (strains 2457T or YSH6000) or S. flexneri 5a (strain M90T) by the intrarectal (i.r.) route. Interestingly, all guinea pigs administered these Shigella strains developed severe and acute rectocolitis. They lost approximately 20% of their body weight and developed tenesmus by 24 h after Shigella infection. Shigella invasion and colonization of the distal colon were seen at 24 h but disappeared by 48 h following i.r. infection. Histopathological approaches demonstrated significant damage and destruction of mucosal and submucosal layers, thickened intestinal wall, edema, erosion, infiltration of neutrophils, and depletion of goblet cells in the distal colon. Furthermore, robust expression of IL-8, IL-1beta, and inducible NO synthase mRNA was detected in the colon from 6 to 24 h following Shigella infection. Most importantly, in our new shigellosis model, guinea pigs vaccinated with an attenuated S. flexneri 2a SC602 strain possessing high levels of mucosal IgA Abs showed milder symptoms of bacillary dysentery than did animals receiving PBS alone after Shigella infection. In the guinea pig, administration of Shigella by i.r. route induces acute inflammation, making this animal model useful for assessing the protective efficacy of Shigella vaccine candidates. PMID- 17277156 TI - Receptor for advanced glycation endproducts mediates neutrophil migration across intestinal epithelium. AB - Receptor for advanced glycation endproducts (RAGE) is an Ig superfamily cell surface receptor that interacts with a diverse array of ligands associated with inflammatory responses. In this study, we provide evidence demonstrating that RAGE is involved in inflammatory responses in the intestines. We showed that RAGE is expressed in intestinal epithelial cells, primarily concentrated at the lateral membranes close to the apical cell junction complexes. Although RAGE expression was low in epithelium under normal conditions, this protein was up regulated after treatment with the inflammatory cytokines IFN-gamma and/or TNF alpha. RAGE expression was also elevated in colon tissue samples from patients with inflammatory bowel diseases. Using in vitro transmigration assays, we found that RAGE mediates neutrophil (polymorphonuclear leukocytes (PMN)) adhesion to, and subsequent migration across, intestinal epithelial monolayers. This activity appears to be mediated by the binding of RAGE to the PMN-specific beta(2) integrin CD11b/CD18. Thus, these results provide a novel mechanism for the regulation of PMN transepithelial migration and may suggest a new therapeutic target for intestinal inflammation. PMID- 17277157 TI - Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. AB - GATA-3 plays a critical role in allergic diseases by regulating the release of cytokines from Th2 lymphocytes. However, the molecular mechanisms involved in the regulation of GATA-3 in human T lymphocytes are not yet understood. Using small interfering RNA to knock down GATA-3, we have demonstrated its critical role in regulating IL-4, IL-5, and IL-13 release from a human T cell line. Specific stimulation of T lymphocytes by costimulation of CD3 and CD28 to mimic activation by APCs induces translocation of GATA-3 from the cytoplasm to the nucleus, with binding to the promoter region of Th2 cytokine genes, as determined by chromatin immunoprecipitation. GATA-3 nuclear translocation is dependent on its phosphorylation on serine residues by p38 MAPK, which facilitates interaction with the nuclear transporter protein importin-alpha. This provides a means whereby allergen exposure leads to the expression of Th2 cytokines, and this novel mechanism may provide new approaches to treating allergic diseases. PMID- 17277158 TI - CD43 collaborates with P-selectin glycoprotein ligand-1 to mediate E-selectin dependent T cell migration into inflamed skin. AB - Activated T cell migration into nonlymphoid tissues is initiated by the interactions of P- and E-selectin expressed on endothelial cells and their ligands on T cells. P-selectin glycoprotein ligand-1 (PSGL-1) has been the only E selectin ligand demonstrated to function during the in vivo migration of activated T cells. We show in this study that CD43-deficient Th1 cells, like PSGL 1-deficient cells, exhibited reduced E-selectin-binding activity compared with wild-type cells. Th1 cells with a PSGL-1 and CD43 double deficiency showed even less E-selectin-binding activity. In migration assays in which adoptively transferred cells migrate to inflamed skin P- and E-selectin dependently, CD43 contributed significantly to PSGL-1-independent Th1 cell migration. In addition, in vivo activated T cells from the draining lymph nodes of sensitized mice deficient in PSGL-1 and/or CD43 showed significantly decreased E-selectin-binding activity and migration efficiency, with T cells from double-deficient mice showing the most profound decrease. Collectively, these results demonstrate that the CD43 expressed on activated T cells functions as an E-selectin ligand and thereby mediates T cell migration to inflamed sites, in collaboration with PSGL 1. PMID- 17277159 TI - Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: role of IkappaBalpha kinase and TGF-beta-activated kinase-1. AB - Numerous recent reports suggest that statins (hydroxy-3-methylglutaryl-CoA reductase inhibitors) exhibit potential to suppress tumorigenesis through a mechanism that is not fully understood. Therefore, in this article, we investigated the effects of simvastatin on TNF-alpha-induced cell signaling. We found that simvastatin potentiated the apoptosis induced by TNF-alpha as indicated by intracellular esterase activity, caspase activation, TUNEL, and annexin V staining. This effect of simvastatin correlated with down-regulation of various gene products that mediate cell proliferation (cyclin D1 and cyclooxygenase-2), cell survival (Bcl-2, Bcl-x(L), cellular FLIP, inhibitor of apoptosis protein 1, inhibitor of apoptosis protein 2, and survivin), invasion (matrix mellatoproteinase-9 and ICAM-1), and angiogenesis (vascular endothelial growth factor); all known to be regulated by the NF-kappaB. We found that simvastatin inhibited TNF-alpha-induced NF-kappaB activation, and l-mevalonate reversed the suppressive effect, indicating the role of hydroxy-3-methylglutaryl CoA reductase. Simvastatin suppressed not only the inducible but also the constitutive NF-kappaB activation. Simvastatin inhibited TNF-alpha-induced IkappaBalpha kinase activation, which led to inhibition of IkappaBalpha phosphorylation and degradation, suppression of p65 phosphorylation, and translocation to the nucleus. NF-kappaB-dependent reporter gene expression induced by TNF-alpha, TNFR1, TNFR-associated death domain protein, TNFR associated factor 2, TGF-beta-activated kinase 1, receptor-interacting protein, NF-kappaB-inducing kinase, and IkappaB kinase beta was abolished by simvastatin. Overall, our results provide novel insight into the role of simvastatin in potentially preventing and treating cancer through modulation of IkappaB kinase and NF-kappaB-regulated gene products. PMID- 17277160 TI - Glucocorticoid conditioning of myeloid progenitors enhances TLR4 signaling via negative regulation of the phosphatidylinositol 3-kinase-Akt pathway. AB - The immunomodulatory effects of glucocorticoids (GCs) have been described as bimodal, with high levels of GCs exerting immunosuppressive effects and low doses of GCs being immunopermissive. While the mechanisms used by GCs to achieve immunosuppression have been investigated intensely, the molecular mechanisms underlying the permissive effects of GCs remain uncharacterized. Herein, we demonstrate that GC conditioning during the differentiation of myeloid progenitors into macrophages (Mphis) results in their enhanced LPS responsiveness, demonstrated by an overexpression of the inflammatory cytokines TNF-alpha, IL-6, and IL-12. Inflammatory cytokine overexpression resulted from an increased activation of NF-kappaB and the MAPK signaling cascade and a reduced activation of the PI3K-Akt pathway following LPS stimulation. GC conditioning during Mphi differentiation induced an increase in the expression of SHIP1, a phosphatase that negatively regulates the PI3K signaling pathway. Small interfering RNA-mediated knockdown of SHIP1 expression increased PI3K-dependent Akt activation and subsequently decreased inflammatory cytokine expression, suggesting GC-mediated up-regulation of SHIP1 expression is responsible for the augmentation in inflammatory cytokine production following LPS stimulation. We also show that splenic Mphis purified from normal mice that were implanted with timed-release GC pellets exhibited an enhanced LPS responsiveness and increased SHIP1 expression, indicating that GCs can regulate SHIP1 expression in vivo. Our results suggest that minor fluctuations in physiological levels of endogenous GCs can program endotoxin-responsive hemopoietic cells during their differentiation by regulating their sensitivity to stimulation. PMID- 17277161 TI - K-ras is critical for modulating multiple c-kit-mediated cellular functions in wild-type and Nf1+/- mast cells. AB - p21(ras) (Ras) proteins and GTPase-activating proteins (GAPs) tightly modulate extracellular growth factor signals and control multiple cellular functions. The specific function of each Ras isoform (H, N, and K) in regulating distinct effector pathways, and the role of each GAP in negatively modulating the activity of each Ras isoform in myeloid cells and, particularly, mast cells is incompletely understood. In this study, we use murine models of K-ras- and Nf1 deficient mice to examine the role of K-ras in modulating mast cell functions and to identify the role of neurofibromin as a GAP for K-ras in this lineage. We find that K-ras is required for c-kit-mediated mast cell proliferation, survival, migration, and degranulation in vitro and in vivo. Furthermore, the hyperactivation of these cellular functions in Nf1(+/-) mast cells is decreased in a K-ras gene dose-dependent fashion in cells containing mutations in both loci. These findings identify K-ras as a key effector in multiple mast cell functions and identify neurofibromin as a GAP for K-ras in mast cells. PMID- 17277162 TI - IgE modulates neutrophil survival in asthma: role of mitochondrial pathway. AB - The high-affinity IgE receptor (FcepsilonRI) has recently been reported to be expressed by neutrophils in atopic asthmatic individuals, leading to speculations that IgE could influence biological functions of these cells. In this study, we demonstrate that monomeric human IgE delayed spontaneous apoptosis of primary human neutrophils from atopic asthmatics in vitro. This effect was not dependent on FcepsilonRI cross-linking or autocrine release of soluble mediators; however, it was associated with increased expression of the antiapoptotic myeloid cell leukemia-1 protein, retention of the proapoptotic molecule Bax in the cytoplasm, decreased release of Smac from mitochondria, and reduced caspase-3 activity. Taken together, our results indicate that in vitro IgE can delay programmed cell death of neutrophils from allergic asthmatics and this may possibly contribute to neutrophilic inflammation in atopic asthma. PMID- 17277164 TI - Selective activation of Fyn/PI3K and p38 MAPK regulates IL-4 production in BMMC under nontoxic stress condition. AB - Mast cells have the ability to react to multiple stimuli, implicating these cells in many immune responses. Specific signals from the microenvironment in which mast cells reside can activate different molecular events that govern distinct mast cells responses. We previously demonstrated that hydrogen peroxide (H(2)O(2)) promotes IL-4 and IL-6 mRNA production and potentates FcepsilonRI induced cytokine release in rat basophilic leukemia RBL-2H3 cells. To further evaluate the effect of an oxidative microenvironment (which is physiologically present in an inflammatory site) on mast cell function and the molecular events responsible for mast cell cytokine production in this environment, we analyzed the effect of H(2)O(2) treatment on IL-4 production in bone marrow-derived, cultured mast cells. Our findings show that nanomolar concentrations of H(2)O(2) induce cytokine secretion and enhance IL-4 production upon FcepsilonRI triggering. Oxidative stimulation activates a distinct signal transduction pathway that induces Fyn/PI3K/Akt activation and the selective phosphorylation of p38 MAP kinase. Moreover, H(2)O(2) induces AP-1 and NFAT complexes that recognize the IL-4 promoter. The absence of Fyn and PI3K or the inhibition of p38 MAPK activity demonstrated that they are essential for H(2)O(2)-driven IL-4 production. These findings show that mast cells can respond to an oxidative microenvironment by initiating specific signals capable of eliciting a selective response. The findings also demonstrate the dominance of the Fyn/p38 MAPK pathway in driving IL-4 production. PMID- 17277163 TI - Signaling in lipopolysaccharide-induced stabilization of formyl peptide receptor 1 mRNA in mouse peritoneal macrophages. AB - To identify the TLR4-initiated signaling events that couple to formyl peptide receptor (FPR)1 mRNA stabilization, macrophages were treated with LPS along with a selection of compounds targeting several known signaling pathways. Although inhibitors of protein tyrosine kinases, MAPKs, and stress-activated kinases had little or no effect on the response to LPS, LY294002 (LY2) and parthenolide (an IkappaB kinase inhibitor) were both potent inhibitors. LY2 but not parthenolide blocked the LPS-induced stabilization of FPR1 mRNA. Although both LY2 and wortmannin effectively blocked PI3K activity, wortmannin had little effect on FPR1 expression and did not modulate the decay of FPR1 mRNA. Moreover, although LY2 was demonstrated to be a potent inhibitor of PI3K activity, a structural analog of LY2, LY303511 (LY3), which did not inhibit PI3K, was equally effective at preventing LPS-stimulated FPR1 expression. The mammalian target of rapamycin activity (measured as phospho-p70S6 kinase) was activated by LPS but not significantly blocked by LY2. In addition, although rapamycin blocked mTOR activity, it did not inhibit FPR1 mRNA expression. Finally, the mechanisms involved in stabilization of FPR1 by LPS could be distinguished from those involved in stabilization of AU-rich mRNAs because the prolonged half-life of FPR1 mRNA was insensitive to the inhibition of p38 MAPK. These findings demonstrate that LY2/LY3 targets a novel TLR4-linked signaling pathway that selectively couples to the stabilization of FPR1 mRNA. PMID- 17277165 TI - Differential biological role of CD3 chains revealed by human immunodeficiencies. AB - The biological role in vivo of the homologous CD3gamma and delta invariant chains within the human TCR/CD3 complex is a matter of debate, as murine models do not recapitulate human immunodeficiencies. We have characterized, in a Turkish family, two new patients with complete CD3gamma deficiency and SCID symptoms and compared them with three CD3gamma-deficient individuals belonging to two families from Turkey and Spain. All tested patients shared similar immunological features such as a partial TCR/CD3 expression defect, mild alphabeta and gammadelta T lymphocytopenia, poor in vitro proliferative responses to Ags and mitogens at diagnosis, and very low TCR rearrangement excision circles and CD45RA(+) alphabeta T cells. However, intrafamilial and interfamilial clinical variability was observed in patients carrying the same CD3G mutations. Two reached the second or third decade in healthy conditions, whereas the other three showed lethal SCID features with enteropathy early in life. In contrast, all reported human complete CD3delta (or CD3epsilon) deficiencies are in infants with life-threatening SCID and very severe alphabeta and gammadelta T lymphocytopenia. Thus, the peripheral T lymphocyte pool was comparatively well preserved in human CD3gamma deficiencies despite poor thymus output or clinical outcome. We propose a CD3delta >> CD3gamma hierarchy for the relative impact of their absence on the signaling for T cell production in humans. PMID- 17277166 TI - A SmD peptide induces better antibody responses to other proteins within the small nuclear ribonucleoprotein complex than to SmD protein via intermolecular epitope spreading. AB - Autoantibody response against the small nuclear ribonucleoprotein (snRNP) complex is a characteristic feature of systemic lupus erythematosus. The current investigation was undertaken to determine whether activation of SmD-reactive T cells by synthetic peptides harboring T cell epitopes can initiate a B cell epitope spreading cascade within the snRNP complex. T cell epitopes on SmD were mapped in A/J mice and were localized to three regions on SmD, within aa 26-55, 52-69, and 86-115. Immunization with synthetic peptides SmD(31-45), SmD(52-66), and SmD(91-110) induced T and B cell responses to the peptides, with SmD(31-45) inducing the strongest response. However, only SmD(52-66) immunization induced T cells capable of reacting with SmD. Analysis of sera by immunoprecipitation assays showed that intermolecular B cell epitope spreading to U1RNA-associated A ribonucleoprotein and SmB was consistently observed only in the SmD(52-66) immunized mice. Surprisingly, in these mice, Ab responses to SmD were at low levels and transient. In addition, the sera did not react with other regions on SmD, indicating a lack of intramolecular B cell epitope spreading within SmD. Our study demonstrates that T cell responses to dominant epitope on a protein within a multiantigenic complex are capable of inducing B cell responses to other proteins within the complex. This effect can happen without generating a good Ab response to the protein from which the T epitope was derived. Thus caution must be taken in the identification of Ags responsible for initiating autoimmune responses based solely on serological analysis of patients and animals with systemic autoimmune disorders. PMID- 17277167 TI - Expansion of CD4+CD25+and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. AB - Regulatory T cells (Tregs) are thought to affect the severity of various infectious and autoimmune diseases. The incidence of autoimmune disease is higher in fertile women than in men. Thus, we investigated whether Treg numbers were modulated during the menstrual cycle by sex hormones. In fertile nonpregnant women, we detected an expansion of CD4(+)CD25(+)FOXP3(+) Tregs in the late follicular phase of the menstrual cycle. This increase was tightly correlated with serum levels of estradiol and was followed by a dramatic decrease in Treg numbers at the luteal phase. Women who have had recurrent spontaneous abortions (RSA) showed similarly low numbers of Tregs at both the follicular and luteal phases, comparable to numbers we observed in postmenopausal women. In addition to decreased numbers, Tregs from women with RSA were also functionally deficient, as higher numbers were required to exert a similar magnitude of suppression to CD4(+)CD25(+)FOXP3(+) cells from fertile women. Consequently, reproductive failure might result from the inability of Tregs in women with RSA to expand during the preimplantatory phase combined with their lower functional capacity. Additionally, the modulation of Treg numbers we observed in fertile women suggests that the stage of the menstrual cycle should be taken into account when Treg numbers are investigated clinically. PMID- 17277168 TI - Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. AB - CD4(+)CD25(+) T regulatory cells (Tregs) play an essential role in maintaining immunologic homeostasis and preventing autoimmunity. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance to nuclear components. We hypothesized that altered function of CD4(+)CD25(high) Tregs might play a role in the breakdown of immunologic self-tolerance in patients with SLE. In this study, we report a significant decrease in the suppressive function of CD4(+)CD25(high) Tregs from peripheral blood of patients with active SLE as compared with normal donors and patients with inactive SLE. Notably, CD4(+)CD25(high) Tregs isolated from patients with active SLE expressed reduced levels of FoxP3 mRNA and protein and poorly suppressed the proliferation and cytokine secretion of CD4(+) effector T cells in vitro. In contrast, the expression of FoxP3 mRNA and protein and in vitro suppression of the proliferation of CD4(+) effector T cells by Tregs isolated from inactive SLE patients, was comparable to that of normal individuals. In vitro activation of CD4(+)CD25(high) Tregs from patients with active SLE increased FoxP3 mRNA and protein expression and restored their suppressive function. These data are the first to demonstrate a reversible defect in CD4(+)CD25(high) Treg function in patients with active SLE, and suggest that strategies to enhance the function of these cells might benefit patients with this autoimmune disease. PMID- 17277169 TI - IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis. AB - Experimental autoimmune encephalomyelitis (EAE), a T cell-mediated inflammatory disease of the CNS, is a rodent model of human multiple sclerosis. IL-23 is one of the critical cytokines in EAE development and is currently believed to be involved in the maintenance of encephalitogenic responses during the tissue damage effector phase of the disease. In this study, we show that encephalitogenic T cells from myelin oligodendrocyte glycopeptide (MOG)-immunized wild-type (WT) mice caused indistinguishable disease when adoptively transferred to WT or IL-23-deficient (p19 knockout (KO)) recipient mice, demonstrating that once encephalitogenic cells have been generated, EAE can develop in the complete absence of IL-23. Furthermore, IL-12/23 double-deficient (p35/p19 double KO) recipient mice developed EAE that was indistinguishable from WT recipients, indicating that IL-12 did not compensate for IL-23 deficiency during the effector phase of EAE. In contrast, MOG-specific T cells from p19KO mice induced EAE with delayed onset and much lower severity when transferred to WT recipient mice as compared with the EAE that was induced by cells from WT controls. MOG-specific T cells from p19KO mice were highly deficient in the production of IFN-gamma, IL 17A, and TNF, indicating that IL-23 plays a critical role in development of encephalitogenic T cells and facilitates the development of T cells toward both Th1 and Th17 pathways. PMID- 17277170 TI - Drosophila melanogaster Thor and response to Candida albicans infection. AB - We used Drosophila melanogaster macrophage-like Schneider 2 (S2) cells as a model to study cell-mediated innate immunity against infection by the opportunistic fungal pathogen Candida albicans. Transcriptional profiling of S2 cells coincubated with C. albicans cells revealed up-regulation of several genes. One of the most highly up-regulated genes during this interaction is the D. melanogaster translational regulator 4E-BP encoded by the Thor gene. Analysis of Drosophila 4E-BP(null) mutant survival upon infection with C. albicans showed that 4E-BP plays an important role in host defense, suggesting a role for translational control in the D. melanogaster response to C. albicans infection. PMID- 17277171 TI - Genome survey sequencing of the wine spoilage yeast Dekkera (Brettanomyces) bruxellensis. AB - The hemiascomycete yeast Dekkera bruxellensis, also known as Brettanomyces bruxellensis, is a major cause of wine spoilage worldwide. Wines infected with D. bruxellensis develop distinctive, unpleasant aromas due to volatile phenols produced by this species, which is highly ethanol tolerant and facultatively anaerobic. Despite its importance, however, D. bruxellensis has been poorly genetically characterized until now. We performed genome survey sequencing of a wine strain of D. bruxellensis to obtain 0.4x coverage of the genome. We identified approximately 3,000 genes, whose products averaged 49% amino acid identity to their Saccharomyces cerevisiae orthologs, with similar intron contents. Maximum likelihood phylogenetic analyses suggest that the relationship between D. bruxellensis, S. cerevisiae, and Candida albicans is close to a trichotomy. The estimated rate of chromosomal rearrangement in D. bruxellensis is slower than that calculated for C. albicans, while its rate of amino acid evolution is somewhat higher. The proteome of D. bruxellensis is enriched for transporters and genes involved in nitrogen and lipid metabolism, among other functions, which may reflect adaptations to its low-nutrient, high-ethanol niche. We also identified an adenyl deaminase gene that has high similarity to a gene in bacteria of the Burkholderia cepacia species complex and appears to be the result of horizontal gene transfer. These data provide a resource for further analyses of the population genetics and evolution of D. bruxellensis and of the genetic bases of its physiological capabilities. PMID- 17277172 TI - Phosphopantetheinyl transferase CfwA/NpgA is required for Aspergillus nidulans secondary metabolism and asexual development. AB - Polyketide synthases (PKSs) and/or nonribosomal peptide synthetases (NRPSs) are central components of secondary metabolism in bacteria, plants, and fungi. In filamentous fungi, diverse PKSs and NRPSs participate in the biosynthesis of secondary metabolites such as pigments, antibiotics, siderophores, and mycotoxins. However, many secondary metabolites as well as the enzymes involved in their production are yet to be discovered. Both PKSs and NRPSs require activation by enzyme members of the 4'-phosphopantetheinyl transferase (PPTase) family. Here, we report the isolation and characterization of Aspergillus nidulans strains carrying conditional (cfwA2) and null (DeltacfwA) mutant alleles of the cfwA gene, encoding an essential PPTase. We identify the polyketides shamixanthone, emericellin, and dehydroaustinol as well as the sterols ergosterol, peroxiergosterol, and cerevisterol in extracts from A. nidulans large scale cultures. The PPTase CfwA/NpgA was required for the production of these polyketide compounds but dispensable for ergosterol and cerevisterol and for fatty acid biosynthesis. The asexual sporulation defects of cfwA, DeltafluG, and DeltatmpA mutants were not rescued by the cfwA-dependent compounds identified here. However, a cfwA2 mutation enhanced the sporulation defects of both DeltatmpA and DeltafluG single mutants, suggesting that unidentified CfwA dependent PKSs and/or NRPSs are involved in the production of hitherto-unknown compounds required for sporulation. Our results expand the number of known and predicted secondary metabolites requiring CfwA/NpgA for their biosynthesis and, together with the phylogenetic analysis of fungal PPTases, suggest that a single PPTase is responsible for the activation of all PKSs and NRPSs in A. nidulans. PMID- 17277174 TI - Simultaneous detection of Mycobacterium bovis and Mycobacterium tuberculosis in human cerebrospinal fluid. PMID- 17277175 TI - Identification of Staphylococcus species with the VITEK 2 system: the case of Staphylococcus hominis. PMID- 17277173 TI - Developmental regulation of an adhesin gene during cellular morphogenesis in the fungal pathogen Candida albicans. AB - Candida albicans expresses specific virulence traits that promote disease establishment and progression. These traits include morphological transitions between yeast and hyphal growth forms that are thought to contribute to dissemination and invasion and cell surface adhesins that promote attachment to the host. Here, we describe the regulation of the adhesin gene ALS3, which is expressed specifically during hyphal development in C. albicans. Using a combination of reporter constructs and regulatory mutants, we show that this regulation is mediated by multiple factors at the transcriptional level. The analysis of ALS3 promoter deletions revealed that this promoter contains two activation regions: one is essential for activation during hyphal development, while the second increases the amplitude of this activation. Further deletion analyses using the Renilla reniformis luciferase reporter delineate the essential activation region between positions -471 and -321 of the promoter. Further 5' or 3' deletions block activation. ALS3 transcription is repressed mainly by Nrg1 and Tup1, but Rfg1 contributes to this repression. Efg1, Tec1, and Bcr1 are essential for the transcriptional activation of ALS3, with Tec1 mediating its effects indirectly through Bcr1 rather than through the putative Tec1 sites in the ALS3 promoter. ALS3 transcription is not affected by Cph2, but Cph1 contributes to full ALS3 activation. The data suggest that multiple morphogenetic signaling pathways operate through the promoter of this adhesin gene to mediate its developmental regulation in this major fungal pathogen. PMID- 17277176 TI - Selecting a genetic region for molecular analysis of hepatitis B virus transmission. PMID- 17277177 TI - DNA looping kinetics analyzed using diffusive hidden Markov model. AB - Tethered particle experiments use light microscopy to measure the position of a micrometer-sized bead tethered to a microscope slide via an approximately micrometer-length polymer, to infer the behavior of the invisible polymer. Currently, this method is used to measure rate constants of DNA loop formation and breakdown mediated by repressor protein that binds to the DNA. We report a new technique for measuring these rates using a modified hidden Markov analysis that directly incorporates the diffusive motion of the bead, which is an inherent complication of tethered particle motion because it occurs on a timescale between the sampling frequency and the looping time. We compare looping lifetimes found with our method, which are consistent over a range of sampling frequencies, to those obtained via the traditional threshold-crossing analysis, which vary depending on how the raw data are filtered in the time domain. Our method does not involve such filtering, and so can detect short-lived looping events and sudden changes in looping behavior. PMID- 17277178 TI - Point-like protrusion as a prestalk intermediate in membrane fusion pathway. AB - The widely accepted pathway of membrane fusion begins with the fusion stalk representing the initial intermediate of hemifusion. The lipid structures preceding hemifusion and their possible influence on fusion kinetics were not addressed. Here, we suggest the point-like protrusion as a prestalk fusion intermediate, which has energy lower than that of stalk and, therefore, does not limit the fusion rate. We demonstrate that by calculating the energy of the point like protrusion, which depends on the lipid monolayer elastic parameters and the strength of the intermembrane hydration repulsion. The point-like protrusion completes the fusion-through-hemifusion model of membrane merger. PMID- 17277179 TI - Electrocatalytic oxidation of guanine, guanosine, and guanosine monophosphate. AB - The electrochemical behavior of guanine, guanosine, and guanosine monophosphate (GMP) at redox polymer film modified indium tin oxide electrodes is examined by voltammetry and redox titration. Utilizing the redox polymer-coated electrodes as indicator electrodes, a new method for measuring the oxidation potentials, based on monitoring their catalytic oxidation by different redox polymer coated electrodes at different pH, was proposed in this work. The oxidation potentials of 0.81 V and 1.02 V versus normal hydrogen electrode were determined for guanine and guanosine/GMP under physiological conditions, the lowest oxidation potentials ever reported, to our knowledge. PMID- 17277180 TI - A cell-based model exhibiting branching and anastomosis during tumor-induced angiogenesis. AB - This work describes the first cell-based model of tumor-induced angiogenesis. At the extracellular level, the model describes diffusion, uptake, and decay of tumor-secreted pro-angiogenic factor. At the cellular level, the model uses the cellular Potts model based on system-energy reduction to describe endothelial cell migration, growth, division, cellular adhesion, and the evolving structure of the stroma. Numerical simulations show: 1), different tumor-secreted pro angiogenic factor gradient profiles dramatically affect capillary sprout morphology; 2), average sprout extension speeds depend on the proximity of the proliferating region to the sprout tip, and the coordination of cellular functions; and 3), inhomogeneities in the extravascular tissue lead to sprout branching and anastomosis, phenomena that emerge without any prescribed rules. This model provides a quantitative framework to test hypotheses on the biochemical and biomechanical mechanisms that control tumor-induced angiogenesis. PMID- 17277181 TI - Electrophoresis of positioned nucleosomes. AB - We present in this article an original approach to compute the electrophoretic mobility of rigid nucleo-protein complexes like nucleosomes. This model allows us to address theoretically the influence of complex position along DNA, as well as wrapped length of DNA on the electrophoretic mobility of the complex. The predictions of the model are in qualitative agreement with experimental results on mononucleosomes assembled on short DNA fragments (<400 bp). Influences of additional experimental parameters like gel concentration, ionic strength, and effective charges are also discussed in the framework of the model, and are found to be qualitatively consistent with experiments when available. Based on the present model, we propose a simple semi-empirical formula describing positioning of nucleosomes as seen through electrophoresis. PMID- 17277182 TI - Response to bistability in apoptosis: roles of bax, bcl-2, and mitochondrial permeability transition pores. PMID- 17277183 TI - Protein secondary structure and orientation in silk as revealed by Raman spectromicroscopy. AB - Taking advantage of recent advances in polarized Raman microspectroscopy, and based on a rational decomposition of the amide I band, the conformation and orientation of proteins have been determined for cocoon silks of the silkworms Bombyx mori and Samia cynthia ricini and dragline silks of the spiders Nephila clavipes and Nephila edulis. This study distinguished between band components due to beta-sheets, beta-turns, 3(1)-helices, and unordered structure for the four fibers. For B. mori, the beta-sheet content is 50%, which matches the proportion of residues that form the GAGAGS fibroin motifs. For the Nephila dragline and S. c. ricini cocoon, the beta-sheet content (36-37% and 45%, respectively) is higher than the proportion of residues that belong to polyalanine blocks (18% and 42%, respectively), showing that adjacent GGA motifs are incorporated into the beta sheets. Nephila spidroins contain fewer beta-sheets and more flexible secondary structures than silkworm fibroins. The amorphous polypeptide chains are preferentially aligned parallel to the fiber direction, although their level of orientation is much lower than that of beta-sheets. Overall, the results show that the four silks exhibit a common molecular organization, with mixtures of different amounts of beta-sheets and flexible structures, which are organized with specific orientation levels. PMID- 17277184 TI - 2,2,2-Trifluoroethanol changes the transition kinetics and subunit interactions in the small bacterial mechanosensitive channel MscS. AB - 2,2,2-Trifluoroethanol (TFE), a low-dielectric solvent, has recently been used as a promising tool to probe the strength of intersubunit interactions in membrane proteins. An analysis of inner membrane proteins of Escherichia coli has identified several SDS-resistant protein complexes that separate into subunits upon exposure to TFE. One of these was the homo-heptameric stretch-activated mechanosensitive channel of small conductance (MscS), a ubiquitous component of the bacterial turgor-regulation system. Here we show that a substantial fraction of MscS retains its oligomeric state in cold lithium-dodecyl-sulfate gel electrophoresis. Exposure of MscS complexes to 10-15 vol % TFE in native membranes or nonionic detergent micelles before lithium-dodecyl-sulfate electrophoresis results in a complete dissociation into monomers, suggesting that at these concentrations TFE by itself disrupts or critically compromises intersubunit interactions. Patch-clamp analysis of giant E. coli spheroplasts expressing MscS shows that exposure to TFE in lower concentrations (0.5-5.0 vol %) causes leftward shifts of the dose-response curves when applied extracellularly, and rightward shifts when added from the cytoplasmic side. In the latter case, TFE increases the rate of tension-dependent inactivation and lengthens the process of recovery to the resting state. MscS responses to pressure ramps of different speeds indicate that in the presence of TFE most channels reside in the resting state and only at tensions near the activation threshold does TFE dramatically speed up inactivation. The effect of TFE is reversible as normal channel activity returns 15-30 min after a TFE washout. We interpret the observed midpoint shifts in terms of asymmetric partitioning of TFE into the membrane and distortion of the bilayer lateral pressure profile. We also relate the increased rate of inactivation and subunit separation with the capacity of TFE to perturb buried interhelical contacts in proteins and discuss these effects in the framework of the proposed gating mechanism of MscS. PMID- 17277185 TI - Further evidence for the absence of polyproline II stretch in the XAO peptide. AB - It has been suggested that the alanine-based peptide with sequence Ac-XX-[A](7) OO-NH(2), termed XAO where X denotes diaminobutyric acid and O denotes ornithine, exists in a predominantly polyproline-helix (P(II)) conformation in aqueous solution. In our recent work, we demonstrated that this "polyproline conformation" should be regarded as a set of local conformational states rather than as the overall conformation of the molecule. In this work, we present further evidence to support this statement. Differential scanning calorimetry measurements showed only a very small peak in the heat capacity of an aqueous solution of XAO at 57 degrees C, whereas the suggested transition to the P(II) structure should occur at approximately 30 degrees C. We also demonstrate that the temperature dependence of the (3)J(HNHalpha) coupling constants of the alanine residues can be explained qualitatively in terms of Boltzmann averaging over all local conformational states; therefore, this temperature dependence proves that a conformational transition does not occur. Canonical MD simulations with the solvent represented by the generalized Born model, and with time averaged NMR-derived restraints, demonstrate the presence of an ensemble of structures with a substantial amount of local P(II) conformational states but not with an overall P(II) conformation. PMID- 17277186 TI - Studying molecular motor-based cargo transport: what is real and what is noise? AB - Noise is a major problem in analyzing tracking data of cargos moved by molecular motors. We use Bayesian statistics to incorporate what is known about the noise in parsing the trajectory of a cargo into a series of constant velocity segments. Tracks with just noise and no underlying motion are fit with constant velocity segments to produce a calibration curve of fit quality versus average segment duration. Fits to tracks of moving cargos are compared to the calibration curves with similar noise. The fit with the optimum number of constant velocity states has the least number of segments needed to match the fit quality of the calibration curve. We have tested this approach using tracks with known underlying motion generated by computer simulations and with a specially designed in vitro experiment. We present the results of using this parsing approach to analyze transport of lipid droplets in Drosophila embryos. PMID- 17277187 TI - Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-response element binding proteins. AB - cAMP-response element binding (CREB) proteins are involved in transcriptional regulation in a number of cellular processes (e.g., neural plasticity and circadian rhythms). The CREB family contains activators and repressors that may interact through positive and negative feedback loops. These loops can be generated by auto- and cross-regulation of expression of CREB proteins, via CRE elements in or near their genes. Experiments suggest that such feedback loops may operate in several systems (e.g., Aplysia and rat). To understand the functional implications of such feedback loops, which are interlocked via cross-regulation of transcription, a minimal model with a positive and negative loop was developed and investigated using bifurcation analysis. Bifurcation analysis revealed diverse nonlinear dynamics (e.g., bistability and oscillations). The stability of steady states or oscillations could be changed by time delays in the synthesis of the activator (CREB1) or the repressor (CREB2). Investigation of stochastic fluctuations due to small numbers of molecules of CREB1 and CREB2 revealed a bimodal distribution of CREB molecules in the bistability region. The robustness of the stable HIGH and LOW states of CREB expression to stochastic noise differs, and a critical number of molecules was required to sustain the HIGH state for days or longer. Increasing positive feedback or decreasing negative feedback also increased the lifetime of the HIGH state, and persistence of this state may correlate with long-term memory formation. A critical number of molecules was also required to sustain robust oscillations of CREB expression. If a steady state was near a deterministic Hopf bifurcation point, stochastic resonance could induce oscillations. This comparative analysis of deterministic and stochastic dynamics not only provides insights into the possible dynamics of CREB regulatory motifs, but also demonstrates a framework for understanding other regulatory processes with similar network architecture. PMID- 17277188 TI - Dynamics of synaptic SfiI-DNA complex: single-molecule fluorescence analysis. AB - A single-molecule analysis was applied to study the dynamics of synaptic and presynaptic DNA-protein complexes (binding of two DNA and one DNA duplex, respectively). In the approach used in this study, the protein was tethered to a surface, allowing a freely diffusing fluorescently labeled DNA to bind to the protein, thus forming a presynaptic complex. The duration of fluorescence burst is the measure of the characteristic lifetime of the complex. To study the formation of the synaptic complex, the two SfiI-bound duplexes with the labeled donor and acceptor were used. The synaptic complex formation by these duplexes was detected by the fluorescence resonance energy transfer approach. The duration of the fluorescence resonance energy transfer burst is the measure of the characteristic lifetime of the synaptic complex. We showed that both synaptic and presynaptic complexes have characteristic dissociation times in the range of milliseconds, with the synaptic SfiI-DNA complex having the shorter dissociation time. Comparison of the off-rate data for the synaptic complex with the rate of DNA cleavage led to the hypothesis that the complex is very dynamic, so the formation of an enzymatically active synaptic complex is a rather rare event in these series of conformational transitions. PMID- 17277189 TI - Infrared spectroscopic study of stratum corneum model membranes prepared from human ceramides, cholesterol, and fatty acids. AB - The outermost layer of the skin, the stratum corneum, consists of corneocytes surrounded by lipid domains. The main lipid classes in stratum corneum are cholesterol, ceramides (CER), and free fatty acids forming two crystalline lamellar phases. However, only limited information is available on whether the various lipid classes participate in the same crystalline lattices or if separate domains are formed within the lipid lamellae. In this article infrared spectroscopic studies are reported of hydrated mixtures prepared from cholesterol, human CER, and free fatty acids. Evaluation of the methylene stretching vibrations revealed a conformational disordering starting at approximately 60 degrees C for all mixtures. Examination of the rotational ordering (scissoring and rocking vibrations) of mixtures prepared from equimolar cholesterol and CER with a variation in the level of free fatty acids showed that at lower free fatty acid content orthorhombic and hexagonal domains coexist in the lipid lamellae. Increasing the fatty acid level to an equimolar cholesterol/CER/fatty acid mixture reveals the dominant presence of an orthorhombic lattice, confirming x-ray diffraction studies. Replacing the protonated free fatty acid chains by their perdeuterated counterparts demonstrates that free fatty acids and CER participate in the same orthorhombic lattice up to a level of slightly less than 1:1:0.75 cholesterol/CER/free fatty acids molar ratio but that free fatty acids also form separate domains within the lipid lamellae at equimolar ratios at room temperature. However, no evidence for this has been observed at 32 degrees C. Extrapolating these findings to the situation in stratum corneum led us conclude that in stratum corneum, fatty acids and CER participate in the orthorhombic lattice at 32 degrees C, the skin temperature. PMID- 17277190 TI - ADP regulates movements of mitochondria in neurons. AB - Mitochondria often reside in subcellular regions with high metabolic demands. We examined the mechanisms that can govern the relocation of mitochondria to these sites in respiratory neurons. Mitochondria were visualized using tetramethylrhodamineethylester, and their movements were analyzed by applying single-particle tracking. Intracellular ATP ([ATP](i)) was assessed by imaging the luminescence of luciferase, the fluorescence of the ATP analog TNP-ATP, and by monitoring the activity of K(ATP) channels. Directed movements of mitochondria were accompanied by transient increases in TNP-ATP fluorescence. Application of glutamate and hypoxia reversibly decreased [ATP](i) levels and inhibited the directed transport. Injections of ATP did not rescue the motility of mitochondria after its inhibition by hypoxia. Introduction of ADP suppressed mitochondrial movements and occluded the effects of subsequent hypoxia. Mitochondria decreased their velocity in the proximity of synapses that correlated with local [ATP](i) depletions. Using a model of motor-assisted transport and Monte Carlo simulations, we showed that mitochondrial traffic is more sensitive to increases in [ADP](i) than to [ATP](i) depletions. We propose that consumption of synaptic ATP can produce local increases in [ADP](i) and facilitate the targeting of mitochondria to synapses. PMID- 17277191 TI - Association free energy of dipalmitoylphosphatidylserines in a mixed dipalmitoylphosphatidylcholine membrane. AB - Blood coagulation is strongly dependent on the binding of vitamin K-dependent proteins to cell membranes containing phosphatidylserine (PS) via gamma carboxyglutamic acid (Gla) domains. The process depends on calcium, which can induce nonideal behavior in membranes through domain formation. Such domain separation mediated by Ca(2+) ions or proteins can have an important contribution to the thermodynamics of the interaction between charged peripheral proteins and oppositely charged membranes. To characterize the properties of lipid-lipid interactions, molecular dynamics, and free energy simulations in a mixed bilayer membrane containing dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine were carried out. The free energy of association between dipalmitoylphosphatidylserines in the environment of dipalmitoylphosphatidylcholines has been calculated by using a novel approach to the dual topology technique of the PS-PC hybrid. Two different methods, free energy perturbation and thermodynamic integration, were used to calculate the free energy difference. In thermodynamic integration runs three schemes were applied to evaluate the integral at the limits of lambda --> 0 or lambda --> 1. Our studies show that the association of two PSs in the environment of PCs is repulsive in the absence of Ca(2+) and becomes favorable in their presence. We also show that the mixed component membrane should exhibit nonideal behavior that will lead to PS clustering. PMID- 17277192 TI - Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. AB - Integrin-mediated adhesion is regulated by multiple features of the adhesive surface, including its chemical composition, topography, and physical properties. In this study we investigated integrin lateral clustering, as a mechanism to control integrin functions, by characterizing the effect of nanoscale variations in the spacing between adhesive RGD ligands on cell spreading, migration, and focal adhesion dynamics. For this purpose, we used nanopatterned surfaces, containing RGD-biofunctionalized gold dots, surrounded by passivated gaps. By varying the spacing between the dots, we modulated the clustering of the associated integrins. We show that cell-surface attachment is not sensitive to pattern density, whereas the formation of stable focal adhesions and persistent spreading is. Thus cells plated on a 108-nm-spaced pattern exhibit delayed spreading with repeated protrusion-retraction cycles compared to cells growing on a 58-nm pattern. Cell motility on these surfaces is erratic and nonpersistent, leaving thin membrane tethers bound to the RGD pattern. Dynamic molecular profiling indicated that the adhesion sites formed with the 108-nm pattern undergo rapid turnover and contain reduced levels of zyxin. These findings indicate that a critical RGD density is essential for the establishment of mature and stable integrin adhesions, which, in turn, induce efficient cell spreading and formation of focal adhesions. PMID- 17277193 TI - Evidence for outer hair cell driven oscillatory fluid flow in the tunnel of corti. AB - Outer hair cell (OHC) somatic motility plays a key role in mammalian cochlear frequency selectivity and hearing sensitivity, but the mechanism of cochlear amplification is not well understood and remains a matter of controversy. We have visualized and quantified the effects of electrically evoked OHC somatic motility within the gerbil organ of Corti using an excised cochlear preparation. We found that OHC motility induces oscillatory motion of the medial olivocochlear fibers where they cross the tunnel of Corti (ToC) in their course to innervate the OHCs. We show that this motion is present at physiologically relevant frequencies and remains at locations distal to the OHC excitation point. We interpret this fiber motion to be the result of oscillatory fluid flow in the ToC. We show, using a simple one-dimensional hydromechanical model of the ToC, that a fluid wave within the tunnel can travel without significant attenuation for distances larger than the wavelength of the cochlear traveling wave at its peak. This ToC fluid wave could interact with the cochlear traveling wave to amplify the motion of the basilar membrane. The ToC wave could also provide longitudinal coupling between adjacent sections of the basilar membrane, and such coupling may be critical for cochlear amplification. PMID- 17277196 TI - Bradycardic therapy improves left ventricular function and remodeling in dogs with coronary embolization-induced chronic heart failure. AB - Both beta-adrenergic blockade and bradycardia may contribute to the therapeutic effect of beta-blockers in chronic heart failure (CHF). This study tested the relative importance of bradycardia by comparing cilobradine (Cilo), a sinus node inhibitor, with a beta-blocker, metoprolol (Meto), in an established canine model of CHF. Dogs were chronically instrumented for hemodynamic and left ventricular (LV) volume measurements. CHF was created by daily coronary embolization via a chronically implanted coronary (left anterior descending coronary artery) catheter. After establishment of CHF, control (n=6), Meto (30 mg/day, n=5), Cilo (low) (1 mg/kg/day, n=5), or Cilo (high) (3 mg/kg/day, n=5) was given orally for 12 weeks. Systemic hemodynamics, echocardiography, and pressure volume analysis were measured at baseline, at CHF, and 3 months after treatment in an awake state. Protein levels of cardiac sarcoplasmic reticulum calcium-ATPase (SERCA2a), ryanodine receptor (RyR2), and Na+-Ca2+ exchanger (NCX1) were measured by Western blot. RyR2 protein kinase A (PKA) phosphorylation was determined by back phosphorylation. After 12 weeks, Meto and Cilo (high and low) produced similar bradycardic effects, accompanied by a significantly improved LV dP/dt versus control [Meto, 2602+/-70; Cilo (low), 2517+/-45; Cilo (high), 2579+/-78; control, 1922+/-115 mm Hg/s; p<0.05]. Both Meto and Cilo (high) normalized protein levels of SERCA2a and NCX1 and reversed PKA hyperphosphorylation of RyR2, in contrast to controls. High-dose cilobradine effectively produced bradycardia and improved cardiac function after CHF, comparable with metoprolol. Restored protein levels of SERCA2a and improved function of RyR2 may be important mechanisms associated with cilobradine therapy. PMID- 17277194 TI - Imaging electrically evoked micromechanical motion within the organ of corti of the excised gerbil cochlea. AB - The outer hair cell (OHC) of the mammalian inner ear exhibits an unusual form of somatic motility that can follow membrane-potential changes at acoustic frequencies. The cellular forces that produce this motility are believed to amplify the motion of the cochlear partition, thereby playing a key role in increasing hearing sensitivity. To better understand the role of OHC somatic motility in cochlear micromechanics, we developed an excised cochlea preparation to visualize simultaneously the electrically-evoked motion of hundreds of cells within the organ of Corti (OC). The motion was captured using stroboscopic video microscopy and quantified using cross-correlation techniques. The OC motion at approximately 2-6 octaves below the characteristic frequency of the region was complex: OHC, Deiter's cell, and Hensen's cell motion were hundreds of times larger than the tectorial membrane, reticular lamina (RL), and pillar cell motion; the inner rows of OHCs moved antiphasic to the outer row; OHCs pivoted about the RL; and Hensen's cells followed the motion of the outer row of OHCs. Our results suggest that the effective stimulus to the inner hair cell hair bundles results not from a simple OC lever action, as assumed by classical models, but by a complex internal motion coupled to the RL. PMID- 17277197 TI - Tamoxifen inhibits topoisomerases, depletes mitochondrial DNA, and triggers steatosis in mouse liver. AB - Although tamoxifen can trigger steatohepatitis, the mechanism of steatosis is unclear. We hypothesized that this DNA-intercalating, cationic amphiphilic drug could accumulate within mitochondria to impair fatty acid oxidation, respiration, and mitochondrial DNA relaxation and synthesis. We studied the in vitro effects of tamoxifen on topoisomerases and mouse liver mitochondria and its in vivo hepatic effects in mice treated for 1 to 28 days with a daily dose of tamoxifen reproducing the plasma concentrations observed in humans. In vitro, tamoxifen inhibited topoisomerase-mediated plasmid DNA relaxation. It accumulated 40-fold inside mitochondria and inhibited both respiration and fatty acid oxidation. In vivo, a single dose of tamoxifen inhibited palmitic acid oxidation and hepatic lipoprotein secretion. Tamoxifen administration also decreased mitochondrial DNA synthesis and progressively depleted hepatic mitochondrial DNA, down to 40% of control values at 28 days. The decrease in mitochondrial DNA-encoded respiratory complexes sensitized mitochondria to the inhibitory effects of tamoxifen on mitochondrial respiration. Hepatic steatosis was absent at 5 days, mild at 12 days, and moderate at 28 days. The fatty acid synthase protein was normally expressed at 12 days but was decreased by 52% at 28 days. In conclusion, tamoxifen decreases hepatic triglyceride secretion, and it accumulates electrophoretically in mitochondria, where it impairs beta-oxidation and respiration. Tamoxifen also inhibits topoisomerases and mitochondrial DNA synthesis and progressively depletes hepatic mitochondrial DNA in vivo. These combined effects could decrease fat removal from the liver, thus causing hepatic steatosis despite a secondary down-regulation of hepatic fatty acid synthase expression. PMID- 17277198 TI - Formation of tellurium nanocrystals during anaerobic growth of bacteria that use Te oxyanions as respiratory electron acceptors. AB - Certain toxic elements support the metabolism of diverse prokaryotes by serving as respiratory electron acceptors for growth. Here, we demonstrate that two anaerobes previously shown to be capable of respiring oxyanions of selenium also achieve growth by reduction of either tellurate [Te(VI)] or tellurite [Te(IV)] to elemental tellurium [Te(0)]. This reduction achieves a sizeable stable-Te isotopic fractionation (isotopic enrichment factor [epsilon] = -0.4 to -1.0 per ml per atomic mass unit) and results in the formation of unique crystalline Te(0) nanoarchitectures as end products. The Te(0) crystals occur internally within but mainly externally from the cells, and each microorganism forms a distinctly different structure. Those formed by Bacillus selenitireducens initially are nanorods ( approximately 10-nm diameter by 200-nm length), which cluster together, forming larger ( approximately 1,000-nm) rosettes composed of numerous individual shards ( approximately 100-nm width by 1,000-nm length). In contrast, Sulfurospirillum barnesii forms extremely small, irregularly shaped nanospheres (diameter < 50 nm) that coalesce into larger composite aggregates. Energy dispersive X-ray spectroscopy and selected area electron diffraction indicate that both biominerals are composed entirely of Te and are crystalline, while Raman spectroscopy confirms that they are in the elemental state. These Te biominerals have specific spectral signatures (UV-visible light, Raman) that also provide clues to their internal structures. The use of microorganisms to generate Te nanomaterials may be an alternative for bench-scale syntheses. Additionally, they may also generate products with unique properties unattainable by conventional physical/chemical methods. PMID- 17277199 TI - Green autofluorescence in dinoflagellates, diatoms, and other microalgae and its implications for vital staining and morphological studies. AB - Green autofluorescence (GAF) has been described in the short flagellum of golden and brown algae, the stigma of Euglenophyceae, and cytoplasm of different life stages of dinoflagellates and is considered by some researchers a valuable taxonomic feature for dinoflagellates. In addition, green fluorescence staining has been widely proposed or adopted to measure cell viability (or physiological state) in areas such as apoptosis of phytoplankton, pollutant stresses on algae, metabolic activity of algae, and testing treatment technologies for ships' ballast water. This paper reports our epifluorescence microscopic observations and quantitative spectrometric measurements of GAF in a broad phylogenetic range of microalgae. Our results demonstrate GAF is a common feature of dinoflagellates, diatoms, green algae, cyanobacteria, and raphidophytes, occurs in the cytoplasm and particularly in eyespots, accumulation bodies, spines, and aerotopes, and is caused by molecules other than chlorophyll. GAF intensity increased with time after cell death or fixation and with excitation by blue or UV light and was affected by pH. GAF of microalgae may be only of limited value in taxonomy. It can be strong enough to interfere with the results of green fluorescence staining, particularly when stained samples are observed microscopically. GAF is useful, however, for microscopic study of algal morphology, especially to visualize cellular components such as eyespots, nucleus, aerotopes, spines, and chloroplasts. Furthermore, GAF can be used to visualize and enumerate dinoflagellate cysts in marine and estuarine sediments in the context of anticipating and monitoring harmful algal blooms and in tracking potentially harmful dinoflagellates transported in ships' ballast tanks. PMID- 17277200 TI - shift from acetoclastic to H2-dependent methanogenesis in a west Siberian peat bog at low pH values and isolation of an acidophilic Methanobacterium strain. AB - Methane production and archaeal community composition were studied in samples from an acidic peat bog incubated at different temperatures and pH values. H(2) dependent methanogenesis increased strongly at the lowest pH, 3.8, and Methanobacteriaceae became important except for Methanomicrobiaceae and Methanosarcinaceae. An acidophilic and psychrotolerant Methanobacterium sp. was isolated using H(2)-plus-CO(2)-supplemented medium at pH 4.5. PMID- 17277201 TI - Efficient synthesis of simvastatin by use of whole-cell biocatalysis. AB - Simvastatin is a semisynthetic derivative of the fungal polyketide lovastatin and is an important drug for lowering cholesterol levels in adults. We have developed a one-step, whole-cell biocatalytic process for the synthesis of simvastatin from monacolin J. By using an Escherichia coli strain overexpressing the previously discovered acyltransferase LovD (X. Xie, K. Watanabe, W. A. Wojcicki, C. C. Wang, and Y. Tang, Chem. Biol. 13:1161-1169, 2006), we were able to achieve >99% conversion of monacolin J to simvastatin without the use of any chemical protection steps. The key finding was a membrane-permeable substrate, alpha dimethylbutyryl-S-methyl-mercaptopropionate, that was efficiently utilized by LovD as the acyl donor. The process was scaled up for gram-scale synthesis of simvastatin. We also demonstrated that simvastatin synthesized via this method can be readily purified from the fermentation broth with >90% recovery and >98% purity as determined by high-performance liquid chromatography. Bioconversion using high-cell-density, fed-batch fermentation was also examined. The whole-cell biocatalysis can therefore be an attractive alternative to currently used multistep semisynthetic transformations. PMID- 17277202 TI - Universal sample preparation method for characterization of bacteria by matrix assisted laser desorption ionization-time of flight mass spectrometry. AB - Mass spectrometry has been a very useful method to rapidly identify microorganisms associated with infectious diseases, detect bioterrorism threats, and discriminate among different subtypes of a pathogen. In this study, we developed a universal method for bacterial identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The effects on the mass spectrum of different experimental conditions, including the amount of bacterial cells used and treatment procedures with different solutions, matrix species, and solvents, were examined, and an optimized protocol was developed. Several different bacterial species, including Yersinia pestis, Escherichia coli, Burkholderia cepacia, Bacillus anthracis, and Staphylococcus aureus, which covered the gram-negative and -positive species and spore-producing and non-spore producing species, were analyzed to evaluate the utility of the protocol. The results showed that five different species and different strains of the same species (9 strains of S. aureus and 10 strains of E. coli) could be discriminated clearly by their peak profiles in a mass range of 1,000 to 20,000 Da. This protocol is simple, rapid, and easy to perform; has excellent reproducibility; and is suitable for the construction of a mass spectrum fingerprinting database, which helps in fast bacterial identification via database searching. PMID- 17277203 TI - Effect of lignocellulose-derived inhibitors on growth of and ethanol production by growth-arrested Corynebacterium glutamicum R. AB - In cellulosic ethanol production, pretreatment of a biomass to facilitate enzymatic hydrolysis inevitably yields fermentation inhibitors such as organic acids, furans, and phenols. With representative inhibitors included in the medium at various concentrations, individually or in various combinations, ethanol production by Corynebacterium glutamicum R under growth-arrested conditions was investigated. In the presence of various inhibitors, the 62 to 100% ethanol productivity retained by the C. glutamicum R-dependent method far exceeded that retained by previously reported methods. PMID- 17277205 TI - Consumption of methane and CO2 by methanotrophic microbial mats from gas seeps of the anoxic Black Sea. AB - The deep anoxic shelf of the northwestern Black Sea has numerous gas seeps, which are populated by methanotrophic microbial mats in and above the seafloor. Above the seafloor, the mats can form tall reef-like structures composed of porous carbonate and microbial biomass. Here, we investigated the spatial patterns of CH(4) and CO(2) assimilation in relation to the distribution of ANME groups and their associated bacteria in mat samples obtained from the surface of a large reef structure. A combination of different methods, including radiotracer incubation, beta microimaging, secondary ion mass spectrometry, and catalyzed reporter deposition fluorescence in situ hybridization, was applied to sections of mat obtained from the large reef structure to locate hot spots of methanotrophy and to identify the responsible microbial consortia. In addition, CO(2) reduction to methane was investigated in the presence or absence of methane, sulfate, and hydrogen. The mat had an average delta(13)C carbon isotopic signature of -67.1 per thousand, indicating that methane was the main carbon source. Regions dominated by ANME-1 had isotope signatures that were significantly heavier (-66.4 per thousand +/- 3.9 per thousand [mean +/- standard deviation; n = 7]) than those of the more central regions dominated by ANME-2 ( 72.9 per thousand +/- 2.2 per thousand; n = 7). Incorporation of (14)C from radiolabeled CH(4) or CO(2) revealed one hot spot for methanotrophy and CO(2) fixation close to the surface of the mat and a low assimilation efficiency (1 to 2% of methane oxidized). Replicate incubations of the mat with (14)CH(4) or (14)CO(2) revealed that there was interconversion of CH(4) and CO(2.) The level of CO(2) reduction was about 10% of the level of anaerobic oxidation of methane. However, since considerable methane formation was observed only in the presence of methane and sulfate, the process appeared to be a rereaction of anaerobic oxidation of methane rather than net methanogenesis. PMID- 17277204 TI - Prevalence of Shiga toxin-producing Escherichia coli stx1, stx2, eaeA, and rfbE genes and survival of E. coli O157:H7 in manure from organic and low-input conventional dairy farms. AB - Manure samples were collected from 16 organic (ORG) and 9 low-input conventional (LIC) Dutch dairy farms during August and September 2004 to determine the prevalence of the STEC virulence genes stx(1) (encoding Shiga toxin 1), stx(2) (encoding Shiga toxin 2), and eaeA (encoding intimin), as well as the rfbE gene, which is specific for Escherichia coli O157. The rfbE gene was present at 52% of the farms. The prevalence of rfbE was higher at ORG farms (61%) than at LIC farms (36%), but this was not significant. Relatively more LIC farms were positive for all Shiga toxin-producing E. coli (STEC) virulence genes eaeA, stx(1), and stx(2), which form a potentially highly virulent combination. Species richness of Enterobacteriaceae, as determined by DGGE, was significantly lower in manure positive for rfbE. Survival of a green fluorescent protein-expressing E. coli O157:H7 strain was studied in the manure from all farms from which samples were obtained and was modeled by a biphasic decline model. The time needed to reach the detection limit was predominantly determined by the level of native coliforms and the pH (both negative relationships). Initial decline was faster for ORG manure but leveled off earlier, resulting in longer survival than in LIC manure. Although the nonlinear decline curve could theoretically be explained as the cumulative distribution of an underlying distribution of decline kinetics, it is proposed that the observed nonlinear biphasic pattern of the survival curve is the result of changing nutrient status of the manure over time (and thereby changing competition pressure), instead of the presence of subpopulations differing in the level of resistance. PMID- 17277206 TI - Historical and contemporary NaCl concentrations affect the duration and distribution of lag times from individual spores of nonproteolytic clostridium botulinum. AB - In this study we determined the effect of NaCl concentration during sporulation (0 or 3.0% [wt/vol] added NaCl) and subsequent growth (0 or 2.0% [wt/vol] added NaCl) on the distributions of times associated with various stages of the lag phase of individual spores of nonproteolytic Clostridium botulinum strain Eklund 17B. The effects of NaCl on the probability of germination and the probability of subsequent growth were also determined. Spore populations exhibited considerable heterogeneity at all stages of lag phase for each condition tested. Germination time did not correlate strongly with the times for later stages in the lag phase, such as outgrowth and doubling time. Addition of NaCl to either the sporulation or growth media increased the mean times for, and variability of, all the measured stages of the lag phase (germination, emergence, time to one mature cell, and time to first doubling). There was a synergistic interaction between the inhibitory effects of NaCl in the sporulation medium and the inhibitory effects of NaCl in the subsequent growth medium on the total lag time and each of its stages. Addition of NaCl to either the sporulation medium or the growth medium reduced both the probability of germination and the probability of a germinated spore developing into a mature cell, but the interaction was not synergistic. Spores formed in medium with added NaCl were not better adapted to subsequent growth in suboptimal osmotic conditions than spores formed in medium with no added NaCl were. Knowledge of the distribution of lag times for individual spores and quantification of the biovariability within lag time distributions may provide insight into the underlying mechanisms and can be used to improve predictions of growth in food and to refine risk assessments. PMID- 17277207 TI - Transposon mutagenesis to improve the growth of recombinant Saccharomyces cerevisiae on D-xylose. AB - Saccharomyces cerevisiae L2612 transformed with genes for xylose reductase and xylitol dehydrogenase (XYL1 and XYL2) grows well on glucose but very poorly on d xylose. When a gene for d-xylulokinase (XYL3 or XKS1) is overexpressed, growth on glucose is unaffected, but growth on xylose is blocked. Spontaneous or chemically induced mutants of this engineered yeast that would grow on xylose could, however, be obtained. We therefore used insertional transposon mutagenesis to identify two loci that can relieve this xylose-specific growth inhibition. One is within the open reading frame (ORF) of PHO13, and the other is approximately 500 bp upstream from the TAL1 ORF. Deletion of PHO13 or overexpression of TAL1 resulted in a phenotype similar to the insertional mutation events. Quantitative PCR showed that deletion of PHO13 increased transcripts for TAL1, indicating that the growth inhibition imposed by the overexpression of XYL3 on xylose can be relieved by an overexpression of transcripts for downstream enzymes. These results may be useful in constructing better xylose-fermenting S. cerevisiae strains. PMID- 17277208 TI - Improved fluorescent in situ hybridization method for detection of bacteria from activated sludge and river water by using DNA molecular beacons and flow cytometry. AB - Fluorescent in situ hybridization (FISH) remains a key technique in microbial ecology. Molecular beacons (MBs) are self-reporting probes that have potential advantages over linear probes for FISH. MB-FISH strategies have been described using both DNA-based and peptide nucleic acid (PNA)-based approaches. Although recent reports have suggested that PNA MBs are superior, DNA MBs have some advantages, most notably cost. The data presented here demonstrate that DNA MBs are suitable for at least some FISH applications in complex samples, providing superior discriminatory power compared to that of corresponding linear DNA-FISH probes. The use of DNA MBs for flow cytometric detection of Pseudomonas putida resulted in approximately double the signal-to-noise ratio of standard linear DNA probes when using laboratory-grown cultures and yielded improved discrimination of target cells in spiked environmental samples, without a need for separate washing steps. DNA MBs were also effective for the detection and cell sorting of both spiked and indigenous P. putida from activated sludge and river water samples. The use of DNA MB-FISH presents another increase in sensitivity, allowing the detection of bacteria in environmental samples without the expense of PNA MBs or multilaser flow cytometry. PMID- 17277209 TI - Multiplex PCR assay for detection of Vibrio vulnificus biotype 2 and simultaneous discrimination of serovar E strains. AB - In the present work we develop a multiplex PCR assay for the detection and identification of the fish pathogen Vibrio vulnificus biotype 2 with discriminating potential for zoonotic strains (serovar E). The PCR assay allowed the identification of two new biotype 2 serovar E human isolates from culture collections. Finally, the multiplex was successfully applied to both diagnosis and carrier detection in field samples. PMID- 17277211 TI - Spatial and temporal population dynamics of a naturally occurring two-species microbial community inside the digestive tract of the medicinal leech. AB - The medicinal leech, Hirudo verbana, is one of the simplest naturally occurring models for digestive-tract symbioses, where only two bacterial species, Aeromonas veronii bv. sobria (gamma-Proteobacteria) and a Rikenella-like bacterium (Bacteroidetes), colonize the crop, the largest compartment of the leech digestive tract. In this study, we investigated spatial and temporal changes of the localization and microcolony structure of the native symbionts in the crop, after ingestion of a sterile blood meal, by fluorescence in situ hybridization. The population dynamics differed between the two symbiotic bacteria. A. veronii was detected mainly as individual cells inside the intraluminal fluid (ILF) during 14 days after feeding (daf) unless it was found in association with Rikenella microcolonies. The Rikenella-like bacteria were observed not only inside the ILF but also in association with the luminal surface of the crop epithelium. The sizes of Rikenella microcolonies changed dynamically through the 14-day period. From 3 daf onward, mixed microcolonies containing both species were frequently observed, with cells of both species tightly associating with each other. The sizes of the mixed microcolonies were consistently larger than the size of either single-species microcolony, suggesting a synergistic interaction of the symbionts. Lectin staining with succinylated wheat germ agglutinin revealed that the planktonic microcolonies present in the ILF were embedded in a polysaccharide matrix containing N-acetylglucosamine. The simplicity, symbiont-symbiont interaction, and mixed microcolonies of this naturally occurring, digestive-tract symbiosis lay the foundation for understanding the more complex communities residing in most animals. PMID- 17277210 TI - The antifungal protein AFP from Aspergillus giganteus inhibits chitin synthesis in sensitive fungi. AB - The antifungal protein AFP from Aspergillus giganteus is highly effective in restricting the growth of major human- and plant-pathogenic filamentous fungi. However, a fundamental prerequisite for the use of AFP as an antifungal drug is a complete understanding of its mode of action. In this study, we performed several analyses focusing on the assumption that the chitin biosynthesis of sensitive fungi is targeted by AFP. Here we show that the N-terminal domain of AFP (amino acids 1 to 33) is sufficient for efficient binding of AFP to chitin but is not adequate for inhibition of the growth of sensitive fungi. AFP susceptibility tests and SYTOX Green uptake experiments with class III and class V chitin synthase mutants of Fusarium oxysporum and Aspergillus oryzae showed that deletions made the fungi less sensitive to AFP and its membrane permeabilization effect. In situ chitin synthase activity assays revealed that chitin synthesis is specifically inhibited by AFP in sensitive fungi, indicating that AFP causes cell wall stress and disturbs cell integrity. Further evidence that there was AFP induced cell wall stress was obtained by using an Aspergillus niger reporter strain in which the cell wall integrity pathway was strongly induced by AFP. PMID- 17277212 TI - Use of high-affinity cell wall-binding domains of bacteriophage endolysins for immobilization and separation of bacterial cells. AB - Immobilization and magnetic separation for specific enrichment of microbial cells, such as the pathogen Listeria monocytogenes, depends on the availability of suitable affinity molecules. We report here a novel concept for the immobilization and separation of bacterial cells by replacing antibodies with cell wall-binding domains (CBDs) of bacteriophage-encoded peptidoglycan hydrolases (endolysins). These polypeptide modules very specifically recognize and bind to ligands on the gram-positive cell wall with high affinity. With paramagnetic beads coated with recombinant Listeria phage endolysin-derived CBD molecules, more than 90% of the viable L. monocytogenes cells could be immobilized and recovered from diluted suspensions within 20 to 40 min. Recovery rates were similar for different species and serovars of Listeria and were not affected by the presence of other microorganisms. The CBD-based magnetic separation (CBD-MS) procedure was evaluated for capture and detection of L. monocytogenes from artificially and naturally contaminated food samples. The CBD separation method was shown to be superior to the established standard procedures; it required less time (48 h versus 96 h) and was the more sensitive method. Furthermore, the generalizability of the CBD-MS approach was demonstrated by using specific phage-encoded CBDs specifically recognizing Bacillus cereus and Clostridium perfringens cells, respectively. Altogether, CBD polypeptides represent novel and innovative tools for the binding and capture of bacterial cells, with many possible applications in microbiology and diagnostics. PMID- 17277213 TI - Novel method for rapid assessment of antibiotic resistance in Escherichia coli isolates from environmental waters by use of a modified chromogenic agar. AB - We validated a novel method for screening Escherichia coli resistance to antibiotics in environmental samples using modified Difco MI agar (Becton Dickinson) impregnated with selected antibiotics (tetracycline, ampicillin, cephalexin, and sulfamethoxazole), termed MI-R. This method combines an existing rapid assessment technique for E. coli enumeration with clinical reference data for breakpoint analysis of antibiotic resistance and was developed to address issues encountered when clinical methods are used with environmental samples. Initial trials conducted using strains of E. coli with resistance to the selected antibiotics showed that this method was reproducible and accurate with respect to antibiotic resistance. Trials using wastewater effluent demonstrated the precision of the method, and the levels of resistance found in effluent were directly comparable to the levels of antibiotic resistance determined using the more traditional CLSI (formerly NCCLS) disk susceptibility test. All wastewater isolates growing on MI-R plates were confirmed to be resistant using the CLSI disk susceptibility test. Bacterial resistance to ampicillin (38% +/- 4% overall), sulfamethoxazole, tetracycline (21% +/- 3% overall), and ciprofloxacin (6% +/- 1%) were found in wastewater effluent. A successful trial was also conducted with water collected from the Brisbane River, Australia. The levels of antibiotic resistance in E. coli ranged from 0 to 47% for ampicillin, from 0 to 24% for tetracycline, from 0 to 63% for sulfamethoxazole, and from 0 to 1% for ciprofloxacin, with the highest incidence of resistance associated with wastewater treatment plant discharges. This method has great potential for rapid and representative assessment of antibiotic resistance in E. coli and could allow increased sample analysis, resulting in greater confidence in spatial analysis in environmental studies. PMID- 17277214 TI - Comparison of a reporter assay and immunomagnetic separation real-time reverse transcription-PCR for the detection of enteroviruses in seeded environmental water samples. AB - Two newly developed protocols for infective virus detection were compared to the plaque assay. An immunomagnetic separation procedure coupled with real-time reverse transcription-PCR of viral nucleic acids was developed to identify intact enteroviral particles, and a reporter cell system responding to viral replication based on fluorescent resonance energy transfer for detection of infectious enteroviruses was tested. Both new procedures detected infective viruses in environmental samples at the same level as the plaque assay. PMID- 17277215 TI - Human enteropathogen load in activated sewage sludge and corresponding sewage sludge end products. AB - This study demonstrated a significant reduction in the concentrations of Cryptosporidium parvum and Cryptosporidium hominis oocysts, Giardia lamblia cysts, and spores of human-virulent microsporidia in dewatered and biologically stabilized sewage sludge cake end products compared to those of the respective pathogens in the corresponding samples collected during the sludge activation process. PMID- 17277216 TI - Comparison of levels of inactivation of two isolates of Giardia lamblia cysts by UV light. AB - The effects of 254-nm UV irradiation on two human isolates (WB and H3) of Giardia lamblia cysts were assessed using a collimated beam protocol and a Mongolian gerbil model. The levels of infection of cysts in the gerbils were assessed based on the presence of cysts in feces and the presence and activity of trophozoites in the small intestine of inoculated gerbils. The results suggest that there were differences in the infectivities of the WB and H3 isolates, as well as in susceptibilities of the parasites to UV light. Without UV exposure, gerbils were more readily infected by isolate H3 cysts. After UV exposure of the cysts, however, the gerbils were more susceptible to isolate WB cysts. PMID- 17277217 TI - Erosion from Staphylococcus aureus biofilms grown under physiologically relevant fluid shear forces yields bacterial cells with reduced avidity to collagen. AB - An estimated 65% of infective diseases are associated with the presence of bacterial biofilms. Biofilm-issued planktonic cells promote blood-borne, secondary sites of infection by the inoculation of the infected sites with bacteria from the intravascular space. To investigate the potential role of early detachment events in initiating secondary infections, we studied the phenotypic attributes of Staphylococcus aureus planktonic cells eroding from biofilms with respect to expression of the collagen adhesin, CNA. The collagen-binding abilities of S. aureus have been correlated to the development of osteomyelitis and septic arthritis. In this study, we focused on the impact of CNA expression on S. aureus adhesion to immobilized collagen in vitro under physiologically relevant shear forces. In contrast to the growth phase-dependent adhesion properties characteristic of S. aureus cells grown in suspension, eroding planktonic cells expressed invariant and lower effective adhesion rates regardless of the age of the biofilm from which they originated. These results correlated directly with the surface expression level of CNA. However, subsequent analysis revealed no qualitative differences between biofilms initiated with suspension cells and secondary biofilms initiated with biofilm-shed planktonic cells. Taken together, our findings suggest that, despite their low levels of CNA expression, S. aureus planktonic cells shed from biofilms retain the capacity for metastatic spread and the initiation of secondary infection. These findings demonstrate the need for a better understanding of the phenotypic properties of eroding planktonic cells, which could lead to new therapeutic strategies to target secondary infections. PMID- 17277218 TI - Water transport in intact yeast cells as assessed by fluorescence self-quenching. AB - Intact yeast cells loaded with 5- and-6-carboxyfluorescein were used to assess water transport. The results were similar to those previously reported for protoplasts assessed by using either fluorescence or light scattering, and the activation energies were 8.0 and 15.1 kcal mol(-1) (33.4 and 63.2 kJ mol(-1)) for a strain overexpressing AQY1 aquaporin and a parental strain, respectively. PMID- 17277219 TI - Quantitative real-time PCR detection of toxic Nodularia cyanobacteria in the Baltic Sea. AB - A specific quantitative real-time PCR (qPCR) method was developed for the quantification of hepatotoxin nodularin-producing Nodularia, one of the main bloom-forming cyanobacteria in the Baltic Sea. Specific PCR primers were designed for subunit F of the nodularin synthetase gene (ndaF), which encodes the NdaF subunit of the nodularin synthetase gene complex needed for nodularin production. The qPCR method was applied to water samples (a total of 120 samples) collected from the Baltic Sea in July 2004. As few as 30 ndaF gene copies ml(-1) of seawater could be detected, and thus, the method was very sensitive. The ndaF gene copy numbers and nodularin concentrations were shown to correlate in the Baltic seawater, indicating the constant production of nodularin by Nodularia. This qPCR method for the ndaF gene can be used for detailed studies of Nodularia blooms and their formation. ndaF gene copies and nodularin were detected mostly in the surface water but also in deeper water layers (down to 30 m). Toxic Nodularia blooms are not only horizontally but also vertically widely distributed, and thus, the Baltic fauna is extensively exposed to nodularin. PMID- 17277220 TI - Genetic diversity and potential function of microbial symbionts associated with newly discovered species of Osedax polychaete worms. AB - We investigated the genetic diversity of symbiotic bacteria associated with two newly discovered species of Osedax from Monterey Canyon, CA, at 1,017-m (Osedax Monterey Bay sp. 3 "rosy" [Osedax sp. MB3]) and 381-m (Osedax Monterey Bay sp. 4 "yellow collar") depths. Quantitative PCR and clone libraries of 16S rRNA gene sequences identified differences in the compositions and abundances of bacterial phylotypes associated with the newly discovered host species and permitted comparisons between adult Osedax frankpressi and juveniles that had recently colonized whalebones implanted at 2,891 m. The newly discovered Osedax species hosted Oceanospirillales symbionts that are related to Gammaproteobacteria associated with the previously described O. frankpressi and Osedax rubiplumus (S. K. Goffredi, V. J. Orphan, G. W. Rouse, L. Jahnke, T. Embaye, K. Turk, R. Lee, and R. C. Vrijenhoek, Environ. Microbiol. 7:1369-1378, 2005). In addition, Osedax sp. MB3 hosts a diverse and abundant population of additional bacteria dominated by Epsilonproteobacteria. Ultrastructural analysis of symbiont-bearing root tissues verified the enhanced microbial diversity of Osedax sp. MB3. Root tissues from the newly described host species and O. frankpressi all exhibited collagenolytic enzyme activity, which covaried positively with the abundance of symbiont DNA and negatively with mean adult size of the host species. Members of this unusual genus of bone-eating worms may form variable associations with symbiotic bacteria that allow for the observed differences in colonization and success in whale fall environments throughout the world's oceans. PMID- 17277221 TI - Rapid screening method for analyzing the conjugated linoleic acid production capabilities of bacterial cultures. AB - In this paper we describe a rapid method for identifying bacteria which convert free linoleic acid to conjugated linoleic acid (CLA). This method is based on spectrophotometric detection of CLA and compares well with the standard gas liquid chromatography method. This method should facilitate high-throughput screening of bacterial isolates for the ability to produce conjugated fatty acids. PMID- 17277222 TI - Plasmid replicon typing of commensal and pathogenic Escherichia coli isolates. AB - Despite the critical role of plasmids in horizontal gene transfer, few studies have characterized plasmid relatedness among different bacterial populations. Recently, a multiplex PCR replicon typing protocol was developed for classification of plasmids occurring in members of the Enterobacteriaceae. Here, a simplified version of this replicon typing procedure which requires only three multiplex panels to identify 18 plasmid replicons is described. This method was used to screen 1,015 Escherichia coli isolates of avian, human, and poultry meat origin for plasmid replicon types. Additionally, the isolates were assessed for their content of several colicin-associated genes. Overall, a high degree of plasmid variability was observed, with 221 different profiles occurring among the 1,015 isolates examined. IncFIB plasmids were the most common type identified, regardless of the source type of E. coli. IncFIB plasmids occurred significantly more often in avian pathogenic E. coli (APEC) and retail poultry E. coli (RPEC) than in uropathogenic E. coli (UPEC) and avian and human fecal commensal E. coli isolates (AFEC and HFEC, respectively). APEC and RPEC were also significantly more likely than UPEC, HFEC, and AFEC to possess the colicin-associated genes cvaC, cbi, and/or cma in conjunction with one or more plasmid replicons. The results suggest that E. coli isolates contaminating retail poultry are notably similar to APEC with regard to plasmid profiles, with both generally containing multiple plasmid replicon types in conjunction with colicin-related genes. In contrast, UPEC and human and avian commensal E. coli isolates generally lack the plasmid replicons and colicin-related genes seen in APEC and RPEC, suggesting limited dissemination of such plasmids among these bacterial populations. PMID- 17277223 TI - Tropheryma whipplei in the environment: survey of sewage plant influxes and sewage plant workers. AB - We studied the prevalence of Tropheryma whipplei in influxes to 46 sewage treatment plants and in stool, mouthwash fluids, and dental plaques of 64 healthy workers in those facilities and 146 disease control patients. T. whipplei was found in sewage water, in stool of healthy individuals, and significantly more often in stool of workers exposed to sewage water. PMID- 17277224 TI - Characterization of an Escherichia coli O157:H7 plasmid O157 deletion mutant and its survival and persistence in cattle. AB - Escherichia coli O157:H7 causes hemorrhagic colitis and hemolytic-uremic syndrome in humans, and its major reservoir is healthy cattle. An F-like 92-kb plasmid, pO157, is found in most E. coli O157:H7 clinical isolates, and pO157 shares sequence similarities with plasmids present in other enterohemorrhagic E. coli serotypes. We compared wild-type (WT) E. coli O157:H7 and an isogenic DeltapO157 mutant for (i) growth rates and antibiotic susceptibilities, (ii) survival in environments with various acidity, salt, or heat conditions, (iii) protein expression, and (iv) survival and persistence in cattle following oral challenge. Growth, metabolic reactions, and antibiotic resistance of the DeltapO157 mutant were indistinguishable from those of its complement and the WT. However, in cell competition assays, the WT was more abundant than the DeltapO157 mutant. The DeltapO157 mutant was more resistant to acidic synthetic bovine gastric fluid and bile than the WT. In vivo, the DeltapO157 mutant survived passage through the bovine gastrointestinal tract better than the WT but, interestingly, did not colonize the bovine rectoanal junction mucosa as well as the WT. Many proteins were differentially expressed between the DeltapO157 mutant and the WT. Proteins from whole-cell lysates and membrane fractions of cell lysates were separated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two dimensional gel electrophoresis. Ten differentially expressed approximately 50 kDa proteins were identified by quadrupole-time of flight mass spectrometry and sequence matching with the peptide fragment database. Most of these proteins, including tryptophanase and glutamate decarboxylase isozymes, were related to survival under salvage conditions, and expression was increased by the deletion of pO157. This suggested that the genes on pO157 regulate some chromosomal genes. PMID- 17277225 TI - A novel lux operon in the cryptically bioluminescent fish pathogen Vibrio salmonicida is associated with virulence. AB - The cold-water-fish pathogen Vibrio salmonicida expresses a functional bacterial luciferase but produces insufficient levels of its aliphatic-aldehyde substrate to be detectably luminous in culture. Our goals were to (i) better explain this cryptic bioluminescence phenotype through molecular characterization of the lux operon and (ii) test whether the bioluminescence gene cluster is associated with virulence. Cloning and sequencing of the V. salmonicida lux operon revealed that homologs of all of the genes required for luminescence are present: luxAB (luciferase) and luxCDE (aliphatic-aldehyde synthesis). The arrangement and sequence of these structural lux genes are conserved compared to those in related species of luminous bacteria. However, V. salmonicida strains have a novel arrangement and number of homologs of the luxR and luxI quorum-sensing regulatory genes. Reverse transcriptase PCR analysis suggests that this novel arrangement of quorum-sensing genes generates antisense transcripts that may be responsible for the reduced production of bioluminescence. In addition, infection with a strain in which the luxA gene was mutated resulted in a marked delay in mortality among Atlantic salmon relative to infection with the wild-type parent in single-strain challenge experiments. In mixed-strain competition between the luxA mutant and the wild type, the mutant was attenuated up to 50-fold. It remains unclear whether the attenuation results from a direct loss of luciferase or a polar disturbance elsewhere in the lux operon. Nevertheless, these findings document for the first time an association between a mutation in a structural lux gene and virulence, as well as provide a new molecular system to study Vibrio pathogenesis in a natural host. PMID- 17277226 TI - Vertical transmission of a phylogenetically complex microbial consortium in the viviparous sponge Ircinia felix. AB - Many marine demosponges contain large amounts of phylogenetically complex yet highly sponge-specific microbial consortia within the mesohyl matrix, but little is known about how these microorganisms are acquired by their hosts. Settlement experiments were performed with the viviparous Caribbean demosponge Ircinia felix to investigate the role of larvae in the vertical transmission of the sponge associated microbial community. Inspections by electron microscopy revealed large amounts of morphologically diverse microorganisms in the center of I. felix larvae, while the outer rim appeared to be devoid of microorganisms. In juveniles, microorganisms were found between densely packed sponge cells. Denaturing gradient gel electrophoresis (DGGE) was performed to compare the bacterial community profiles of adults, larvae, and juvenile sponges. Adults and larvae were highly similar in DGGE band numbers and banding patterns. Larvae released by the same adult individual contained highly similar DGGE banding patterns, whereas larvae released by different adult individuals showed slightly different DGGE banding patterns. Over 200 bands were excised, sequenced, and phylogenetically analyzed. The bacterial diversity of adult I. felix and its larvae was comparably high, while juveniles showed reduced diversity. In total, 13 vertically transmitted sequence clusters, hereafter termed "IF clusters," that contained sequences from both the adult sponge and offspring (larvae and/or juveniles) were found. The IF clusters belonged to at least four different eubacterial phyla and one possibly novel eubacterial lineage. In summary, it could be shown that in I. felix, vertical transmission of microorganisms through the larvae is an important mechanism for the establishment of the sponge-microbe association. PMID- 17277227 TI - Dynamics and biodiversity of populations of lactic acid bacteria and acetic acid bacteria involved in spontaneous heap fermentation of cocoa beans in Ghana. AB - The Ghanaian cocoa bean heap fermentation process was studied through a multiphasic approach, encompassing both microbiological and metabolite target analyses. A culture-dependent (plating and incubation, followed by repetitive sequence-based PCR analyses of picked-up colonies) and culture-independent (denaturing gradient gel electrophoresis [DGGE] of 16S rRNA gene amplicons, PCR DGGE) approach revealed a limited biodiversity and targeted population dynamics of both lactic acid bacteria (LAB) and acetic acid bacteria (AAB) during fermentation. Four main clusters were identified among the LAB isolated: Lactobacillus plantarum, Lactobacillus fermentum, Leuconostoc pseudomesenteroides, and Enterococcus casseliflavus. Other taxa encompassed, for instance, Weissella. Only four clusters were found among the AAB identified: Acetobacter pasteurianus, Acetobacter syzygii-like bacteria, and two small clusters of Acetobacter tropicalis-like bacteria. Particular strains of L. plantarum, L. fermentum, and A. pasteurianus, originating from the environment, were well adapted to the environmental conditions prevailing during Ghanaian cocoa bean heap fermentation and apparently played a significant role in the cocoa bean fermentation process. Yeasts produced ethanol from sugars, and LAB produced lactic acid, acetic acid, ethanol, and mannitol from sugars and/or citrate. Whereas L. plantarum strains were abundant in the beginning of the fermentation, L. fermentum strains converted fructose into mannitol upon prolonged fermentation. A. pasteurianus grew on ethanol, mannitol, and lactate and converted ethanol into acetic acid. A newly proposed Weissella sp., referred to as "Weissella ghanaensis," was detected through PCR-DGGE analysis in some of the fermentations and was only occasionally picked up through culture-based isolation. Two new species of Acetobacter were found as well, namely, the species tentatively named "Acetobacter senegalensis" (A. tropicalis-like) and "Acetobacter ghanaensis" (A. syzygii-like). PMID- 17277228 TI - Selective phylogenetic analysis targeting 16S rRNA genes of hyperthermophilic archaea in the deep-subsurface hot biosphere. AB - International drilling projects for the study of microbial communities in the deep-subsurface hot biosphere have been expanded. Core samples obtained by deep drilling are commonly contaminated with mesophilic microorganisms in the drilling fluid, making it difficult to examine the microbial community by 16S rRNA gene clone library analysis. To eliminate mesophilic organism contamination, we previously developed a new method (selective phylogenetic analysis [SePA]) based on the strong correlation between the guanine-plus-cytosine (G+C) contents of the 16S rRNA genes and the optimal growth temperatures of prokaryotes, and we verified the method's effectiveness (H. Kimura, M. Sugihara, K. Kato, and S. Hanada, Appl. Environ. Microbiol. 72:21-27, 2006). In the present study we ascertained SePA's ability to eliminate contamination by archaeal rRNA genes, using deep-sea hydrothermal fluid (117 degrees C) and surface seawater (29.9 degrees C) as substitutes for deep-subsurface geothermal samples and drilling fluid, respectively. Archaeal 16S rRNA gene fragments, PCR amplified from the surface seawater, were denatured at 82 degrees C and completely digested with exonuclease I (Exo I), while gene fragments from the deep-sea hydrothermal fluid remained intact after denaturation at 84 degrees C because of their high G+C contents. An examination using mixtures of DNAs from the two environmental samples showed that denaturation at 84 degrees C and digestion with Exo I completely eliminated archaeal 16S rRNA genes from the surface seawater. Our method was quite useful for culture-independent community analysis of hyperthermophilic archaea in core samples recovered from deep-subsurface geothermal environments. PMID- 17277229 TI - Genetic variability in prostaglandin synthesis, fish intake and risk of colorectal polyps. AB - Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Metabolism of omega-6 (n-6) PUFAs results in the production of pro-inflammatory mediators whereas downstream products of omega-3 (n-3) PUFAs have lower inflammatory activity. Elevated n-3 PUFA intake from dietary fish may be associated with lower risk of colorectal neoplasia among those with genetic variants resulting in higher levels of pro-inflammatory mediators. We investigated interactions between dietary fish intake and polymorphisms in cyclooxygenase (COX)-1, COX-2, ALOX5 and PGIS in a case-control study of adenomas (N = 522), hyperplastic polyps (N = 194) and polyp-free controls (N = 626). Polyp risk did not differ by fish intake. A suggested interaction with fish intake was observed for COX-1 P17L. Among those who were homozygous wild type, increasing fish intake was associated with a modestly reduced risk of adenoma, whereas among those with at least one variant allele, the reverse trend was observed (p interaction = 0.08). The interaction was statistically significant when non steroidal anti-inflammatory drug (NSAID) use was also taken into account: among those with COX-1 17PP genotypes, high fish intake and regular NSAID use was associated with a decreased risk compared with low fish intake and low NSAID use (odds ratio = 0.60, 95% confidence interval 0.33-1.09). The opposite association was observed among those with COX-1 17PL or LL genotypes (p-interaction = 0.04). Our results suggest that the effects of dietary n-3 PUFA intake and NSAID use may differ by genetic variation in COX-1. PMID- 17277231 TI - Bax and Bak genes are essential for maximum apoptotic response by curcumin, a polyphenolic compound and cancer chemopreventive agent derived from turmeric, Curcuma longa. AB - Curcumin, an active ingredient of turmeric (Curcuma longa), inhibits proliferation and induces apoptosis in cancer cells, but the sequence of events leading to cell death is poorly defined. The objective of this study was to examine the molecular mechanisms by which multidomain pro-apoptotic Bcl-2 family members Bax and Bak regulate curcumin-induced apoptosis using mouse embryonic fibroblasts (MEFs) deficient in Bax, Bak or both genes. Curcumin treatment resulted an increase in the protein levels of both Bax and Bak, and mitochondrial translocation and activation of Bax in MEFs to trigger drop in mitochondrial membrane potential, cytosolic release of apoptogenic molecules [cytochrome c and second mitochondria-derived activator of caspases (Smac)/direct inhibitor of apoptosis protein-binding protein with low isoelectric point], activation of caspase-9 and caspase-3 and ultimately apoptosis. Furthermore, MEFs derived from Bax and Bak double-knockout (DKO) mice exhibited even greater protection against curcumin-induced release of cytochrome c and Smac, activation of caspase-3 and caspase-9 and induction of apoptosis compared with wild-type MEFs or single knockout Bax(-/-) or Bak(-/-) MEFs. Interestingly, curcumin treatment also caused an increase in the protein level of apoptosis protease-activating factor-1 in wild-type MEFs. Smac N7 peptide enhanced curcumin-induced apoptosis, whereas Smac siRNA inhibited the effects of curcumin on apoptosis. Mature form of Smac sensitized Bax and Bak DKO MEFs to undergo apoptosis by acting downstream of mitochondria. The present study demonstrates the role of Bax and Bak as a critical regulator of curcumin-induced apoptosis and over-expression of Smac as interventional approaches to deal with Bax- and/or Bak-deficient chemoresistant cancers for curcumin-based therapy. PMID- 17277230 TI - Nucleophosmin suppresses oncogene-induced apoptosis and senescence and enhances oncogenic cooperation in cells with genomic instability. AB - Cells from patients with genomic instability syndromes have high predisposition to cancer. However, little is known about whether these mutant cells have high susceptibility to oncogenic transformation. We have tested the hypothesis that a defect in maintaining genome integrity is necessary but not sufficient alone for oncogenic transformation and needs to collaborate with other signals in order to produce full oncogenic transformation. Using genetically matched primary cells deficient for the Fanconi complementation group C gene (Fancc) and the ataxia telangiectasia mutated gene (Atm), we found that certain forms of oncogenic activation and cooperation require a combination of genomic instability with increased expression of nucleophosmin (NPM) to prevent oncogenic stress-induced apoptosis or senescence. Intriguingly, co-expression of c-Myc and NPM leads to a synergistic increase in the proliferation rate in Fancc-/- or Atm-/- cells. Analysis of p53 stabilization and activation by c-Myc demonstrates that over expression of NPM significantly reduces the accumulation of the activated p53 but not the stability of p53. Moreover, NPM is shown to enhance transforming activity of co-expressed Myc and Ras in wild-type and, to a greater degree, in Fancc-/- or Atm-/- cells, suggesting a role in oncogenic cooperation. Finally, a partial knockdown of NPM is sufficient to cause massive apoptosis in Fancc-/- or Atm-/- cells co-expressing c-Myc and Ras while sparing untransformed cells. Our study demonstrates a novel mechanism of NPM tumorigenesis by establishing NPM as a crucial inhibitor of oncogene-induced apoptosis and senescence. PMID- 17277232 TI - Leukocyte polycyclic aromatic hydrocarbon-DNA adduct formation and colorectal adenoma. AB - Consumption of charbroiled red meat and meat-derived polycyclic aromatic hydrocarbons (PAHs) has been associated with risk of colorectal adenoma, a precursor of colorectal cancer. Furthermore, leukocyte PAH-DNA adduct levels have been demonstrated to increase in response to charbroiled red meat intake but to date there have been no studies that have investigated the relationship between leukocyte PAH-DNA adduct levels and risk of colorectal adenoma. We investigated the relation of leukocyte PAH-DNA adduct formation and colorectal adenoma in a clinic-based case-control study of colorectal adenomas. The study comprised 82 cases of colorectal adenoma and 111 polyp-free controls, none of whom were current smokers. Leukocyte PAH-DNA adducts were measured by a sensitive chemiluminescence immunoassay using an antiserum elicited against DNA modified with (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydro benzo[a]pyrene that recognizes several PAHs bound to human DNA. Leukocyte PAH-DNA adduct levels were higher among colorectal adenoma cases (median, 1.4 adducts per 10(8) nucleotides) than polyp-free controls (median, 1.2 adducts per 10(8) nucleotides) (P = 0.02). There was a positive association between PAH-DNA adduct level and adenoma prevalence: each unit increase in PAH-DNA adduct level (per 10(8) nucleotides) was associated with an odds ratio (OR) of 1.5 [95% confidence interval (CI), 1.1-2.2]. In addition, a comparison of the lowest quartile for PAH DNA adduct level with the highest quartile yielded an OR of 2.8 (95% CI, 1.2-6.5; P(trend) = 0.048) for risk of colorectal adenoma. These data support a link between PAH exposure and colorectal adenoma. PMID- 17277233 TI - Prostaglandin receptor EP2 is responsible for cyclooxygenase-2 induction by prostaglandin E2 in mouse skin. AB - The EP2 prostanoid receptor is one of the four subtypes of receptors for prostaglandin E2 (PGE2). We previously reported that deletion of EP2 led to resistance to chemically induced mouse skin carcinogenesis, whereas overexpression of EP2 resulted in enhanced tumor development. The purpose of this study was to investigate the underlying molecular mechanisms. We found that EP2 knockout mice had reduced cyclooxygenase-2 (COX-2) expression after 12-O tetradecanoylphorbol-13-acetate (TPA) treatment compared with wild-type (WT) mice. Further, primary keratinocytes from EP2 transgenic mice had increased COX-2 expression after either TPA or PGE2 treatment and COX-2 expression was blocked by 10 microM SQ 22,536, an adenylate cyclase inhibitor. EP2 knockout mice had significantly decreased, whereas EP2 transgenic mice had significantly increased PGE2 production in response to a single treatment of TPA. Cyclic AMP response element-binding protein (CREB) phosphorylation was elevated to a greater extent in keratinocytes from EP2 transgenic mice compared with those of WT mice following PGE2 treatment. A protein kinase A (PKA) inhibitor reduced PGE2 mediated CREB phosphorylation in keratinocytes from EP2 transgenic mice. Furthermore, we found that there was no CREB phosphorylation in EP2 knockout mice following PGE2 treatment. PGE2-induced DNA synthesis (cell proliferation) was significantly decreased in keratinocytes from EP2 knockout mice following pretreatment with 10 microM SQ 22,536. Taken together, EP2 activation of the PKA/CREB-signaling pathway is responsible for keratinocyte proliferation and our findings reveal a positive feedback loop between COX-2 and PGE2 that is mediated by the EP2 receptor. PMID- 17277235 TI - Processed meat intake, CYP2A6 activity and risk of colorectal adenoma. AB - Red and processed meat intake is associated with increased risks of both colorectal adenoma and cancer. Processed meats contain nitrate and nitrite, precursors of N-nitroso compounds (NOCs); furthermore, meats cooked at high temperatures contain heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Specific NOC, HCA and PAH are mutagens and animal carcinogens. We conducted a case-control study of 146 cases of colorectal adenoma, diagnosed at sigmoidoscopy or colonoscopy, and 228 polyp-free controls. We calculated odds ratios (ORs) [and 95% confidence intervals (CIs)] and found a 2-fold increased risk in the highest, compared with the lowest, quartile of processed meat intake (95% CI = 1.0-4.0). We estimated nitrate and nitrite intake from meat using published data from the literature as well as from actual measurements of meats analyzed recently. We evaluated the interaction of processed meat and nitrate plus nitrite intake with CYP2A6 activity, an enzyme able to metabolize some NOC to their carcinogenic form. Results for both methods of estimating nitrate and nitrite intake were similar; compared with the lowest, the highest quartile based on measured values was associated with a 2-fold elevated risk (95% CI = 1.0-3.9). Adjustment for the HCA 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx) attenuated the association (OR = 1.6, 95% CI = 0.8-3.2), but other HCA and PAH had minimal effect. Higher CYP2A6 activity was not associated with risk and there was no evidence of an interaction of CYP2A6 activity with nitrate and nitrite intake. Our results suggest that nitrite and nitrate intake from processed meat intake increases the risk of colorectal adenoma after accounting for HCA and PAH. PMID- 17277236 TI - A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett's esophagus and esophageal adenocarcinoma. AB - Oxidative stress appears to be important in the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Single-nucleotide polymorphisms (SNPs) of antioxidant enzyme genes may play a part in determining individual susceptibility to these diseases. The Factors Influencing the Barrett's Adenocarcinoma Relationship (FINBAR) study is a population-based, case control study of BE and EAC in Ireland. DNA from EAC (n = 207), BE (> or =3 cm BE at endoscopy with specialized intestinal metaplasia on biopsy, n = 189) and normal population controls (n = 223) were analyzed. Several SNPs spanning the genes for glutathione S-transferase P1 (GSTP1), manganese superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPX2) were genotyped using multiplex polymerase chain reaction and SNaPshottrade mark. The chi(2) test was used to compare genotype and allele frequencies between case and control subjects. Linkage disequilibrium between SNPs was quantified using Lewontin's D' value and haplotype frequency estimates obtained using Haploview. Eleven SNPs were genotyped (six for GSTP1, three for MnSOD and two for GPX2); all were in Hardy Weinberg equilibrium. None was significantly associated with EAC or BE even before Bonferroni correction. Odds ratios for EAC for individual SNPs ranged from 0.68 [95% confidence interval (CI) 0.43-1.08] to 1.25 (95% CI 0.73-2.16), and for BE from 0.84 (95% CI 0.52-1.30) to 1.30 (95% CI 0.85-1.97). SNPs in all three genes were in strong linkage disequilibrium (D' > 0.887) but haplotype analysis did not show any significant association with EAC or BE. SNPs involving the GSTP1, MnSOD and GPX2 genes were not associated with BE or EAC. Further studies aimed at identifying susceptibility genes should focus on different antioxidant genes or different pathways. PMID- 17277238 TI - The association between a surgeon's learning curve with endovascular aortic aneurysm repair and previous institutional experience. AB - The purpose of the present study was to determine whether an institution's prior endovascular experience influenced the learning curve of subsequent surgeons. A prospective analysis of the initial 70 endovascular abdominal aortic aneurysm repair (EVAR) cases attempted by an individual surgeon was performed with the primary outcome variable being achievement and 30-day maintenance of initial clinical success. Along with standard statistical analyses, the cumulative sum failure method (CUSUM) was used to analyze the learning curve, with a predetermined acceptable failure rate of 10%. Seventy elective EVAR cases were performed by this surgeon during a 4-year period (2000-2004) (mean age, 73.7 -/+ 5.4 years; mean aneurysm diameter 63.3 -/+ 7.2 mm). Initial clinical success was achieved in 68 of 70 cases (97%), which differed significantly with that of our initial surgeon (88.5%, P = .01). Causes of failure in the present series included 1 early mortality (1.4%) and 1 case of conversion to open repair with no instances of type I endoleak or endograft limb thrombosis. Both surgeons' cases were plotted sequentially with CUSUM curves revealing a significantly shorter learning curve for the second surgeon. Optimal results were achieved following 10 to 20 EVAR cases, as opposed to 60 cases in the initial series. Such an analysis confirms that as an institution's experience with EVAR increases, an individual surgeon's learning curve shortens considerably. PMID- 17277237 TI - Cognitive function after carotid artery revascularization. AB - Clinical investigations designed to contrast the efficacy of carotid endarterectomy (CEA) versus best medical therapy and CEA versus carotid artery stenting (CAS) in patients with carotid artery stenosis have been based on the traditional endpoints of stroke, myocardial infarction, and death. Cognitive function is being increasingly recognized as an important outcome measure that affects patient well-being and functional status. However, it has not been evaluated systematically in the context of carotid revascularization. A decline in cognitive function could occur from microembolic ischemia during surgical dissection (CEA) or intravascular instrumentation (CAS). It could also occur from hypoperfusion during clamping (CEA) or balloon dilation (CAS). Conversely, restoring perfusion could improve cognitive dysfunction that might have occurred from a state of chronic hypoperfusion. It is still unclear whether these complex interactions ultimately result in a net improvement or a deterioration of cognitive function. Furthermore, it is not known whether the 2 methods of carotid revascularization have a differential effect on cognitive outcomes. It is becoming increasingly clear, though, that there is a positive relationship between improvement in cognition and improvement in functional outcome of patients. Vascular surgeons will be well served to remain informed and even actively engaged in the development of this field if they wish to continue providing the high-quality, well-informed care they have traditionally offered to patients with carotid stenosis. PMID- 17277239 TI - Catheter thrombolysis of thrombosed hepatic arteries in liver transplant recipients: predictors of success and role of thrombolysis. AB - Hepatic artery thrombosis is an uncommon complication of liver transplantation. However, it is a major indication for re-transplantation. The use of transcatheter thrombolysis and subsequent surgical revascularization as a graft salvage procedure is discussed. Four of 5 cases (80%) were successful in re establishing flow and uncovering underlying arterial anatomic defects. None were treated definitively by endoluminal measures due to an inability to resolve the underlying anatomic defects. However, 2 of 5 cases (40%) went on to a successful surgical revascularization and represent successful long-term outcome of transcatheter thrombolysis followed by definitive surgical revascularization. We conclude that, definitive endoluminal success cannot be achieved without resolving associated, and possibly instigating, underlying arterial anatomical defects. However, reestablishing flow to the graft can unmask underlying lesions as well as asses surrounding vasculature thus providing anatomical information for a more elective, better planned and definitive surgical revision. PMID- 17277240 TI - Benefits of a supervised exercise program after lower limb bypass surgery. AB - This study evaluated the efficacy of an exercise program after arterial bypass surgery. Patients undergoing bypass surgery were randomized to a control group (group I), with standard preoperative and postoperative care, or the intervention group (group II) with a supervised exercise program of twice-weekly treadmill assessments from 4 to 10 weeks postoperatively. Ankle-brachial pressure indices and hemodynamic measurements were recorded before and after exercise. The mean increase of maximum walking distance was 3.8% in group I and 175.4% in group II (P = .001). There was a significant difference between group I and II in the mean ankle-brachial pressure indices increase at the second assessment (0.08 versus 0.23; P = .02). A supervised exercise program leads to better improvement after lower limb bypass surgery for ischemia, but the feasibility of a formal exercise program would be undermined by the reluctance of patients to participate, both in the short-term and long-term. PMID- 17277241 TI - Patterns of venous reflux and obstruction in patients with skin damage due to chronic venous disease. AB - Identified were characteristics of individuals with skin damage related to chronic venous disease. Patients with chronic venous disease (n = 164) were evaluated with duplex ultrasound imaging and were placed in classes 4, 5, and 6 according to the CEAP classification. Their findings were compared with 100 class 2 controls. The prevalence of deep venous thrombosis was higher in the study group (23.7%) versus controls (5.1%; P < .0001), as was the prevalence of deep, perforator, and combined patterns of disease (P < .0001, P < .0007, and P < .0001). The mean duration of disease in controls 2 was shorter compared with the study group (P = .0019). The prevalence of reflux and obstruction within the study group was higher than in controls (P = .0021). Skin changes accurately reflect severity of chronic venous disease. Superficial and perforator vein reflux is the major cause of disease. PMID- 17277242 TI - Combined endovenous ablation and transilluminated powered phlebectomy: is less invasive better? AB - This study was undertaken to evaluate the evolution of operative vein approaches from combined "open" saphenous stripping-stab avulsion phlebectomy to combined "minimally invasive" endovenous ablation-transilluminated powered phlebectomy with a focus on comparing clinical outcomes. All patients undergoing a combined operative approach for concomitant saphenous vein insufficiency and associated varicose tributary veins between January 1, 1998 and December 31, 2005 were identified. Patients were stratified by operative approach into 3 groups: combined saphenous vein stripping-stab avulsion phlebectomy (STRIP-PHLEB); combined saphenous vein stripping-transilluminated phlebectomy (STRIP-TPP); and combined endovenous ablation-transilluminated phlebectomy (EVAB-TPP). Clinical volume, indications, technical details, and complications were retrospectively reviewed. Over the 8-year period, there were 72 limbs in 59 patients treated with STRIP-PHLEB, 92 limbs in 81 patients with STRIP-TPP, and 99 limbs in 76 patients with EVAB-TPP, with a time-dependent transition in operative techniques noted. There was no difference in distribution of CEAP clinical classification between groups, overall with most limbs in the C2-C4 categories (93.1%) and fewer in the C5-C6 categories (6.9%). There was no difference in overall complication rates between STRIP-PHLEB and EVAB-TPP, although the distribution of complications did shift with a trend toward more wound problems noted in procedures involving saphenous stripping (STRIP-PHLEB 5.6%, STRIP-TPP 6.5%, EVAB-TPP 2.0%; P = NS), and more hematomas in procedures involving transilluminated powered phlebectomy (STRIP-PHLEB 5.6%, STRIP-TPP 16.3%, EVAB-TPP 6.9%; P < .05; see Table 2). Complications associated with the endovenous ablation portion were low including technical inability to cannulate 1.6%, saphenous re-cannulation 2.4%, hematoma 2.4%, severe phlebitis 3.1%, venous thromboembolism 0.8%, and no wound or thermal injury problems. With the shift of combined operative vein approaches for concomitant saphenous vein insufficiency and varicose tributary veins towards "minimally invasive" techniques the overall complication rate has remained unchanged. While combined endovenous ablation-transilluminated phlebectomy offers some advantage of "less" invasiveness, this perceived benefit should be balanced against unchanged overall risk over traditional operative approaches. PMID- 17277243 TI - Paradoxical neutrophil elastase release in endovascular abdominal aortic aneurysm repair. AB - Endovascular repair of abdominal aortic aneurysm potentially avoids problems associated with prolonged aortic cross-clamping that occurs with open repair, but it appears to have its own biologic consequences, which may relate to neutrophil elastase release. Blood samples of consecutive patients undergoing open or endovascular abdominal aneurysm repair were analyzed for neutrophil elastase/alpha(1)-antitrypsin complex and free elastase. Free elastase rose from baseline and fell quickly in open repair patients, returning to baseline by 144 hours. In the endovascular repair group, it continued to increase for up to 144 hours. Bound elastase increased to 24 hours, returning to baseline in endovascular repair patients by 72 hours, but remaining elevated in open repair patients at 144 hours. Open repair patients showed raised elastase/alpha(1) antitrypsin complex and initial raised free elastase levels. High free elastase levels in endovascular repair patients may reflect less bound elastase and may paradoxically lead to a prolonged inflammatory postoperative response. PMID- 17277244 TI - Novel repair of venous aneurysms secondary to arteriovenous dialysis fistulae. AB - This report describes the surgical management of 12 hemodialysis patients with arteriovenous fistulae in whom non-infected, fusiform venous aneurysms developed that compromised access for dialysis. The venous aneurysmal changes were too extensive to permit excision and primary veno-venous anastomosis. To avoid the use of synthetic interpositional grafts, the venous aneurysms were left in situ and reduced in size to match the diameters of the veins entering and exiting the aneurysms. After decompression, the lumens of the venous aneurysms were reduced by firing staple lines along the longitudinal axes of the venous aneurysms and excision of the aneurysmal tissue anterior to the staple lines. Twenty-eight aneurysms were repaired by this method of reduction aneurysmoplasty, in 15 operations on 12 patients over the past 10 years. There were no wound infections or dehiscences and no bleeding or hematomas. After the operations, the arteriovenous fistulae were used continuously for hemodialysis until the patients died (7 patients for 36 months -/+ 28 SD), were lost to follow-up (1 patient at 30 days postoperatively), until the arteriovenous fistulae thrombosed following revision of the arteriovenous anastomosis (1 patient at 41 months postoperatively), or until the arteriovenous fistulae was ligated to relieve pain in the upper arm (1 patient at 6 months postoperatively). Two patients continue to use their arteriovenous fistulae until and including the time of this report at 10 and 11 months, respectively. Reduction aneurysmoplasty as described in this report offers an effective and low-risk option for the management of venous aneurysms secondary to arteriovenous fistulae in hemodialysis patients. PMID- 17277245 TI - Endovascular abdominal aortic aneurysm sizing and case planning using the TeraRecon Aquarius workstation. AB - The gold standard for preoperative evaluation of an aortic aneurysm is a computed tomography angiogram (CTA). Three-dimensional reconstruction and analysis of the computed tomography data set is enormously helpful, and even sometimes essential, in proper sizing and planning for endovascular stent graft repair. To a large extent, it has obviated the need for conventional angiography for morphologic evaluation. The TeraRecon Aquarius workstation (San Mateo, Calif) represents a highly sophisticated but user-friendly platform utilizing a combination of task specific hardware and software specifically designed to rapidly manipulate large Digital Imaging and Communications in Medicine (DICOM) data sets and provide surface-shaded and multiplanar renderings in real-time. This article discusses the basics of sizing and planning for endovascular abdominal aortic aneurysm repair and the role of 3-dimensional analysis using the TeraRecon workstation. PMID- 17277246 TI - Endovascular management of a ruptured splenic artery aneurysm. PMID- 17277247 TI - Treatment of bleeding varicose veins of the scrotum with percutaneous coil embolization of the left spermatic vein: a case report. AB - Percutaneous coil embolization of the spermatic vein offers a minimally invasive method for treating symptomatic varicose veins of the scrotum. We describe the case of a 63-year-old man with multiple comorbidities and persistent bleeding from scrotal varicosities. Venography revealed significant left spermatic vein reflux and a large left varicocele. Percutaneous coil embolization of the left spermatic vein completely resolved the bleeding from the left side of the patient's scrotum. Although many vascular specialists possess the technical skills to perform this procedure, they may not be familiar with its use in the treatment of scrotal varicosities and varicoceles. PMID- 17277248 TI - Endovascular treatment of false aneurysm of the thyrocervical trunk. AB - The thyrocervical trunk is the second superior branch off the subclavian artery. Pseudoaneurysm of the thyrocervical trunk has been reported after attempted internal jugular vein cannulation for central venous or hemodialysis access. The treatment of pseudoaneurysms of the thyrocervical trunk depends on the findings from color flow Doppler ultrasonography and angiography. Although pseudoaneurysms of the thyrocervical trunk are rare, the treatment options should be clear. Surgical ligation is an effective technique that is safe and well-defined, but control through a cervical incision may be difficult. Endovascular treatment of the pseudoaneurysm may be accomplished with coil embolization of the artery, which is described. PMID- 17277249 TI - Esophageal stent erosion into the common carotid artery. AB - A pseudoaneurysm of the common carotid artery was found with computed tomography in a 62-year-old woman with an esophageal stent that had eroded through her skin. The pseudoaneurysm was treated with a self-expanding nitinol stent; after massive hemoptysis, an endograft was placed on the pseudoaneurysm. The patient then underwent ligation of the left common carotid artery, proximal to the carotid bulb, and excision of the endograft and previously placed coils. The esophageal stent wires were so that they could no longer impinge the common carotid artery. PMID- 17277250 TI - Endovascular stent-graft repair of penetrating descending thoracic aortic ulcer. AB - This article presents a case in which covered stent-graft cuffs were used to treat a penetrating ulcer of the descending thoracic aorta. An 80-year-old woman presented with penetrating ulcer in the descending thoracic aorta. Two endovascular stent graft cuffs were used for total exclusion of the penetrating ulcer, because the patient had a high operative risk. Her postoperative course was uneventful, and follow-up computed tomographic angiography showed complete coverage of the ulcer without evidence of leak. This case demonstrates that endoluminal stent-graft repair of penetrating descending thoracic aortic ulcers is a safe, less-invasive treatment, especially for elderly, high-risk patients. PMID- 17277251 TI - Optimal medical management of peripheral arterial disease. PMID- 17277254 TI - Current issues in health policy: a primer for the orthopaedic surgeon. AB - Political, social, and economic forces occupy an increasingly larger role in health care. It is essential that orthopaedic surgeons become familiar with the ever-changing landscape within which they practice. Greater comprehension of the current issues in health policy will enable practitioners to appreciate these issues and understand the importance of the involvement of the AAOS in the political process. Five topics in particular will continue to have a great impact on the practice of orthopaedic surgery: the flawed Medicare payment formula, implementation of a pay-for-performance program, the creation of gainsharing agreements between hospitals and physicians, the medical liability crisis, and the importance of advocacy with the political action committee of the AAOS. PMID- 17277252 TI - Setting the bar in phase II trials: the use of historical data for determining "go/no go" decision for definitive phase III testing. AB - PURPOSE: Phase II trials aim to determine whether a cancer treatment is sufficiently promising to justify phase III study. Whether an agent is declared promising in a phase II trial depends on prespecified "null" and "alternative" rates of an outcome of interest such as tumor response. In some cases, the null must be determined with reference to historical data. We sought to determine the proportion of phase II trials that require historical data to establish the null and to determine how these historical estimates were derived. EXPERIMENTAL DESIGN: We conducted a systematic review of phase II trials published in the Journal of Clinical Oncology or Cancer in the 3 years to June 2005. Data were extracted following a prespecified protocol. RESULTS: We retrieved 251 papers, of which 117 were found to be ineligible; 70 of 134 included trials (52%) were defined as requiring historical data for design. Nearly half (32, 46%) of these papers did not cite the source of the historical data used, and just 9 (13%) clearly gave a single historical estimate as the rationale for the null. Trials that failed to cite prior data appropriately were significantly more likely to declare an agent to be active (82% versus 33%; P=0.005). No study incorporated statistical methods to account for either sampling error or possible differences in case mix between the phase II sample and the historical cohort. CONCLUSIONS: Many phase II trials require historical data to determine null response rates. Simple guidelines may improve design and reporting of such trials. PMID- 17277255 TI - Double-bundle reconstruction of the anterior cruciate ligament: anatomic and biomechanical rationale. AB - Patients continue to suffer residual pain and instability following anterior cruciate ligament reconstruction. Although overall outcomes of anterior cruciate ligament reconstruction are favorable, improved outcomes can be achieved. Recent biomechanical studies have questioned the ability of conventional single-bundle anterior cruciate ligament constructs to adequately restore normal knee kinematics. Consequently, the use of double-bundle anterior cruciate ligament constructs has been recommended to restore knee stability more effectively. Recent biomechanical data indicate that double-bundle anterior cruciate ligament reconstruction may provide better anteroposterior and rotational knee stability than do conventional single-bundle techniques. Studies are needed to evaluate the clinical impact of double-bundle reconstruction techniques on long-term functional outcomes. PMID- 17277256 TI - Intramedullary nailing of the lower extremity: biomechanics and biology. AB - The intramedullary nail or rod is commonly used for long-bone fracture fixation and has become the standard treatment of most long-bone diaphyseal and selected metaphyseal fractures. To best understand use of the intramedullary nail, a general knowledge of nail biomechanics and biology is helpful. These implants are introduced into the bone remote to the fracture site and share compressive, bending, and torsional loads with the surrounding osseous structures. Intramedullary nails function as internal splints that allow for secondary fracture healing. Like other metallic fracture fixation implants, a nail is subject to fatigue and can eventually break if bone healing does not occur. Intrinsic characteristics that affect nail biomechanics include its material properties, cross-sectional shape, anterior bow, and diameter. Extrinsic factors, such as reaming of the medullary canal, fracture stability (comminution), and the use and location of locking bolts also affect fixation biomechanics. Although reaming and the insertion of intramedullary nails can have early deleterious effects on endosteal and cortical blood flow, canal reaming appears to have several positive effects on the fracture site, such as increasing extraosseous circulation, which is important for bone healing. PMID- 17277257 TI - Evaluation of the elderly patient with an abnormal gait. AB - Distinguishing between the normal gait of the elderly and pathologic gaits is often difficult. Pathologic gaits with neurologic causes include frontal gait, spastic hemiparetic gait, parkinsonian gait, cerebellar ataxic gait, and sensory ataxic gait. Pathologic gaits with combined neurologic and musculoskeletal causes include myelopathic gait, stooped gait of lumbar spinal stenosis, and steppage gait. Pathologic gaits with musculoskeletal causes include antalgic gait, coxalgic gait, Trendelenburg gait, knee hyperextension gait, and other gaits caused by inadequate joint mobility. A working knowledge of the characteristics of these gaits and a systematic approach to observational gait examination can help identify the causes of abnormal gait. Patients with abnormal gait can benefit from the treatment of the primary cause of the disorder as well as by general fall-prevention interventions. Treatable causes of gait disturbance are found in a substantial proportion of patients and include normal-pressure hydrocephalus, vitamin B(12) deficiency, Parkinson's disease, alcoholism, medication toxicity, cervical spondylotic myelopathy, lumbar spinal stenosis, joint contractures, and painful disorders of the lower extremity. PMID- 17277258 TI - Reconstruction of the rheumatoid thumb. AB - Thumb deformities are common manifestations of rheumatoid arthritis and represent a significant source of disability. A clear understanding of the pathophysiology of the disease is essential in directing treatment. Differential diagnosis for flexible deformities includes soft-tissue imbalances as well as tendon ruptures. In its early stages, thumb involvement can be treated nonsurgically or with soft tissue reconstruction. With more advanced disease, arthrodesis and arthroplasty often are required. Isolated interphalangeal involvement is best addressed with arthrodesis. Metacarpophalangeal involvement can be treated with arthroplasty in low-demand patients or with arthrodesis in more active patients. Trapezium resection arthroplasty provides excellent relief for patients with carpometacarpal joint destruction. PMID- 17277259 TI - The 36-item short form. AB - The use of patient-derived, objective outcome measures has expanded substantially within the orthopaedic literature. Quality-of-life instruments are categorized as general health or as condition-specific questionnaires. The Medical Outcomes Study 36-Item Short Form (SF-36) is a general health-based survey of quality of life. It has been validated, is used widely across medical disciplines, and can be self-administered by the patient with reliability. The SF-36 has been implemented to define disease conditions, to determine the effect of treatment, to differentiate the effect of different treatments, and to compare orthopaedic conditions with other medical conditions. However, a bias of lower over upper extremity function has been demonstrated with the SF-36, as have limitations in assessment of certain physical activities of daily living as well as upper and lower limits on the detection of certain changes in quality-of-life status. Nevertheless, with an adequate knowledge of its effectiveness and limitations, the SF-36 can be a useful tool in many branches of orthopaedic surgery. PMID- 17277261 TI - What is the place for placebo in the management of psychogenic disease? PMID- 17277262 TI - An increasing need for early detection of body dysmorphic disorder by all specialties. PMID- 17277263 TI - Overconfidence in warfare. PMID- 17277264 TI - Hubris and Nemesis in heads of government. PMID- 17277265 TI - Forced change of language. PMID- 17277266 TI - Commercial aircraft cabin altitude. PMID- 17277267 TI - Clinical studies in medical journals. PMID- 17277268 TI - 'A brief history of homeopathy'. PMID- 17277269 TI - Inconvenient truths. PMID- 17277270 TI - Bacillary dysentery in Egypt, 1943-1944. PMID- 17277271 TI - Normal hearing tests: is a further appointment really necessary? PMID- 17277272 TI - Gender bias in research. PMID- 17277273 TI - The diagnosis of art: diastrophic dysplasia and Hephaistos. PMID- 17277274 TI - Optimizing diabetes care: perspectives from a practical view point. PMID- 17277275 TI - Training tomorrow's surgeons. PMID- 17277276 TI - Challenges of treating thyroid disease: the need for a revisit. PMID- 17277277 TI - The demise of nursing in the United Kingdom: a warning for medicine. PMID- 17277278 TI - Care closer to home: past mistakes, future opportunities. PMID- 17277279 TI - Health care participants' dualism: are new sub-species evolving? PMID- 17277281 TI - Church, Crown and City: changing fortunes in controlling health care. PMID- 17277280 TI - Illness related deception: social or psychiatric problem? AB - In this paper we question the validity of factitious disorder as a meaningful psychiatric diagnosis. When the diagnosis is used there is often the assumption that the person engaging in the 'deception' is not lying in the traditional sense of being deliberately misleading. Moreover, little is known about the aetiology or psychopathology underlying factitious disorder, and the legitimacy of deception as a mental disorder has been questioned. It is argued that while illness deception may be more common that hitherto assumed, factitious disorder as a distinct type of psychiatric disorder is conceptually flawed, diagnostically impractical and clinically unhelpful and should be dropped from existing nosologies. PMID- 17277282 TI - The tortuous history of the implementation of early ambulation after delivery. PMID- 17277283 TI - Informed consent for elective surgery--what is best practice? PMID- 17277284 TI - Research governance impediments to clinical trials: a retrospective survey. AB - OBJECTIVE: We sought to evaluate the delays, between-centre variations in practice, and opportunity costs attributable to delays in research governance approval of clinical trials in the United Kingdom. DESIGN: Retrospective survey. SETTING: Research and Development (R&D) departments at 50 UK National Health Service hospital trusts governing 57 hospital sites. PARTICIPANTS: R&D departments participating in four randomized multicentre clinical trials coordinated by our Neurosciences Trials Unit. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Median delay between application and research governance approval. RESULTS: Only half of the R&D departments used the UK online R&D form. Only a single copy of the application was required by 96% of R&D departments. The median delay between application and research governance approval was 44 working days (inter-quartile range 23-80). A delay of >20 working days was incurred by 43 applications (75%), of which 24 (56%) were not explicable and 11 (20%) were attributable to local funding negotiations. Based on the trial randomization rates at each centre, 108 patients (17% of all patients randomized) could have been randomized during the delay, at a crude cost to funding agencies of 53,743 pounds; if a four week delay was deemed acceptable, 75 patients (12% of all patients randomized) could have been randomized during unacceptable delays, at a crude cost to funding agencies of 37,700 pounds. CONCLUSIONS: The UK research governance system incurs unacceptably long and costly delays for clinical trials. Urgent reform is needed, including rapid design and uniform implementation of the 'bureaucracy busting' measures in Best Research for Best Health. PMID- 17277285 TI - Fever, haemoptysis and a mass in the heart. PMID- 17277286 TI - The miracle at St Alfege's: seventy years on. PMID- 17277287 TI - Of saving children. PMID- 17277288 TI - Esophageal endoscopic ultrasound/endobronchial ultrasound-guided fine needle aspiration: a new dawn for the respiratory physician? PMID- 17277289 TI - The British 1958 cohort: a message for obstetricians and pediatricians. PMID- 17277290 TI - An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. PMID- 17277291 TI - The carbon footprint of the American Thoracic Society meeting. PMID- 17277292 TI - Asthma mortality in Michigan for the years 2002 to 2005, ages 5-34. PMID- 17277293 TI - Mechanical tooth cleaning before chlorhexidine application. PMID- 17277294 TI - Breastfeeding, weight gain in infancy, and overweight at seven years of age: the prevention and incidence of asthma and mite allergy birth cohort study. AB - Compared with nonbreastfed children, breastfed children tend to have a lower body mass index (BMI) at about 1 year of age. How the BMI of breastfed children develops after the first year when this difference in BMI at 1 year of age is considered is not clear. The authors studied the association between breastfeeding and BMI development from 1 to 7 years of age independently of BMI at 1 year of age. Longitudinal BMI data reported by parents of 2,347 Dutch children born in 1996-1997 who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort study were collected. Linear regression and mixed-effects models were used for data analyses. Mean BMI at 1 year of age was 17.2 kg/m(2) (standard deviation, 1.4). Compared with nonbreastfed children, children breastfed for >16 weeks had a lower BMI at 1 year of age, after adjustment for confounders (beta = -0.22, 95% confidence interval: -0.39, -0.06). The association between breastfeeding and BMI between 1 and 7 years of age was negligible, while a high BMI at 1 year of age was strongly associated with a high BMI between 1 and 7 years of age in the same model. These findings suggest that the lower BMI and lower risk of overweight among breastfed children later in life are already achieved at 1 year of age. PMID- 17277295 TI - Evaluation of the effects of infrared beak trimming in broiler breeder chicks. AB - Detailed behavioural observations were made of broiler breeder chicks after their beaks had been trimmed by an automated infrared treatment at one day of age or by the traditional hot-blade method at one day or seven days, or after they had been sham-trimmed or left untreated. Observations took place immediately after the treatments and at regular intervals until six weeks of age; beak length and bodyweight were also measured regularly. There were no significant effects on the behaviour of the chicks in the first hour after trimming or in the subsequent six weeks. Variability in beak length was low within the treatments and there was significant regrowth, but it was least in the birds that had been hot-blade trimmed at seven days. Both beak-trimming methods were associated with small but significant reductions in bodyweight, with the hot-blade-treated birds being more affected. PMID- 17277296 TI - Relationships between tail biting in pigs and disease lesions and condemnations at slaughter. AB - Two matched case-control studies were performed at an abattoir with a capacity of 780 pigs per hour, each study using the approximately 7000 pigs slaughtered on one day. In the first study, the severity of tail biting and pneumonia were recorded in pigs with bitten or intact tails. In the second study, the tail score, sex, and the presence of pleuritis, externally visible abscesses and trimming were recorded in pigs with bitten or intact tails. In study 1, there was no significant association between the tail score and the percentage of lung tissue affected by lesions typical of enzootic pneumonia, but there was a significant association between the severity of tail biting and the prevalence of lungs with abscesses and/or pleuritic lesions (P<0.0001). In study 2, there were significant associations between the severity of tail biting, and the prevalence of external carcase abscesses and carcase trimming; the carcases of castrated males had evidence of tail biting more frequently than the carcases of females (P<0.05). PMID- 17277297 TI - Effects of premedication with fentanyl and midazolam on mask induction of anaesthesia of dogs with sevoflurane. AB - Fourteen beagles were used to determine the effects of fentanyl and midazolam as a premedicant for mask induction of anaesthesia with sevoflurane. The drugs were administered to each dog in a randomised cross-over design with a seven-day washout period between experiments. After a 15-minute equilibration period, a treatment consisting of fentanyl (10 mug/kg bodyweight) and midazolam (0.2 mg/kg) was given either intravenously or intramuscularly. Anaesthesia was then induced by the use of a facemask with sevoflurane in 100 per cent oxygen at a flow rate of 4 l/minute. Vaporiser settings were increased by 0.8 per cent at 15-second intervals until the value corresponding to 4.8 per cent sevoflurane was achieved. The time to the onset and cessation of involuntary movements, loss of the palpebral reflex, negative response to tail-clamp stimulation, and endotracheal intubation and cardiopulmonary variables were measured. Both the treatments with tentanyl and midazolam resulted in a shorter and smoother induction of anaesthesia than treatment with saline, and the cardiopulmonary changes were smaller and milder. PMID- 17277298 TI - Repair of a salivary duct fistula in a horse without using a stent. AB - A salivary duct fistula in a horse was repaired surgically without using a stent. Seventeen months after the operation the skin incision had healed without complications and the fistula had not recurred. PMID- 17277299 TI - Association between polyarthritis and thrombocytopenia and increased prevalence of vectorborne pathogens in Californian dogs. PMID- 17277300 TI - Fracture of the lumbar vertebrae in two cows. PMID- 17277301 TI - Necrotic vulvovaginitis in dairy cattle in Israel. PMID- 17277302 TI - Effect of infusion of 60 mg/kg oxytetracycline on forelimb flexor tendon contracture in calves. PMID- 17277303 TI - TB in llamas caused by Mycobacterium bovis. PMID- 17277305 TI - Arthrotomy and arthrodesis of the fetlock joint in cattle. PMID- 17277306 TI - Communication skills. PMID- 17277307 TI - Communication skills. PMID- 17277308 TI - Communication skills. PMID- 17277309 TI - Efficacy of haemorrhagic septicaemia alum-precipitated vaccine. PMID- 17277310 TI - Universal newborn hearing screening and early identification of deafness: parents' responses to knowing early and their expectations of child communication development. AB - This article presents results from an interview study of 45 parents/caregivers (representing 27 families) whose infants were correctly identified as deaf during the first phase of the implementation of the national universal Newborn Hearing Screening Programme in England. Average age of children when parents were interviewed was 25 weeks. Two issues are explored: (a) how parents talk about significance of knowing early that their child is deaf and (b) parents' expectations of their child's development in light of early identification. Although results demonstrate clear support from parents' perspective of knowing early, they also identify the psychological complexities of recognizing both the grief and reassurance that early knowledge brings; the risks of early knowledge inducing timetables of expectations that create distress when not met speedily; the extent to which parental models of the developmental advantages of early identification are underpinned by notions of normal speech and the possibility of being like hearing children; and the pervasiveness of deficit and illness models associated with having identified deafness early. Implications for parental support and professional responses are also discussed. PMID- 17277311 TI - An electrostatic/hydrogen bond switch as the basis for the specific interaction of phosphatidic acid with proteins. AB - Phosphatidic acid (PA) is a minor but important phospholipid that, through specific interactions with proteins, plays a central role in several key cellular processes. The simple yet unique structure of PA, carrying just a phosphomonoester head group, suggests an important role for interactions with the positively charged essential residues in these proteins. We analyzed by solid state magic angle spinning 31P NMR and molecular dynamics simulations the interaction of low concentrations of PA in model membranes with positively charged side chains of membrane-interacting peptides. Surprisingly, lysine and arginine residues increase the charge of PA, predominantly by forming hydrogen bonds with the phosphate of PA, thereby stabilizing the protein-lipid interaction. Our results demonstrate that this electrostatic/hydrogen bond switch turns the phosphate of PA into an effective and preferred docking site for lysine and arginine residues. In combination with the special packing properties of PA, PA may well be nature's preferred membrane lipid for interfacial insertion of positively charged membrane protein domains. PMID- 17277312 TI - STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. AB - Interleukin-17 (IL-17)-producing helper T (TH) cells, named as TH(IL-17), TH17, or inflammatory TH (THi), have been recently identified as a novel effector lineage. However, how cytokine signals mediate THi differentiation is unclear. We found that IL-6 functioned to up-regulate IL-23R and that IL-23 synergized with IL-6 in promoting THi generation. STAT3, activated by both IL-6 and IL-23, plays a critical role in THi development. A hyperactive form of STAT3 promoted THi development, whereas this differentiation process was greatly impaired in STAT3 deficient T cells. Moreover, STAT3 regulated the expression of retinoic acid receptor-related orphan receptor gamma-T (RORgamma t), a THi-specific transcriptional regulator; STAT3 deficiency impaired RORgamma t expression and led to elevated expression of T-box expressed in T cells (T-bet) and Forkhead box P3 (Foxp3). Our data thus demonstrate a pathway whereby cytokines regulate THi differentiation through a selective STAT transcription factor that functions to regulate lineage-specific gene expression. PMID- 17277313 TI - A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. AB - Cytochrome P4502S1 (CYP2S1) is expressed at high levels in epithelial tissues and is inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) via the aryl hydrocarbon receptor (AHR). Transcriptional initiation of mouse Cyp2s1 was found to occur at three regions, approximately 198, 102, and 22 nucleotides from the translational initiation codon. Approximately 400 nucleotides upstream of its translational initiation codon, mouse Cyp2s1 contains three overlapping xenobiotic-responsive element (XRE) sequences, which make a major contribution toward dioxin inducibility. Each XRE sequence in this trimeric XRE can bind the AHR/aryl hydrocarbon receptor nuclear translocator (ARNT) dimer in a dioxin dependent fashion in vitro and can mediate dioxin-dependent transcription. Cyp2s1 is also markedly inducible by hypoxia. Induction is dependent on hypoxiainducible factor-1 (HIF-1) and is mediated in large part by three overlapping hypoxia response elements (HREs) embedded within the trimeric XRE segment. Although each HRE within this segment can bind HIF-1alpha/ARNT in vitro, the most 3' HRE contributes the most toward hypoxia inducibility. AHR/ARNT and HIF-1alpha/ARNT dimers bind to the region containing the trimeric XRE segment of the endogenous Cyp2s1 gene in vivo in a dioxin-dependent fashion and hypoxia-dependent fashion, respectively. These observations identify a novel regulatory cassette that mediates changes in Cyp2s1 expression. PMID- 17277314 TI - SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development. AB - In mammals, male sex is determined by the Y-chromosomal gene Sry (sex-determining region of Y chromosome). The expression of Sry and subsequently Sox9 (SRY box containing gene 9) in precursors of the supporting cell lineage results in the differentiation of these cells into Sertoli cells. Sertoli cells in turn orchestrate the development of all other male-specific cell types. To ensure that Sertoli cells differentiate in sufficient numbers to induce normal testis development, the early testis produces prostaglandin D(2) (PGD(2)), which recruits cells of the supporting cell lineage to a Sertoli cell fate. Here we show that the gene encoding prostaglandin D synthase (Pgds), the enzyme that produces PGD(2), is expressed in Sertoli cells immediately after the onset of Sox9 expression. Promoter analysis in silico and in vitro identified a paired SOX/SRY binding site. Interestingly, only SOX9, and not SRY, was able to bind as a dimer to this site and transactivate the Pgds promoter. In line with this, a transgenic mouse model showed that Pgds expression is not affected by ectopic Sry expression. Finally, chromatin immunoprecipitation proved that SOX9 but not SRY binds to the Pgds promoter in vivo. PMID- 17277315 TI - Predicting foot ulcers in patients with diabetes: a systematic review and meta analysis. AB - Clinical guidelines recommend that all patients with diabetes should be screened annually to establish their risk of foot ulceration. The aim of this systematic review was to quantify the predictive value of diagnostic tests, physical signs and elements from the patient's history in relation to diabetic foot ulcers. Observational studies were identified from: electronic databases (MEDLINE, EMBASE and CINAHL); bibliographies of studies meeting the inclusion criteria; review articles and clinical guidelines; direct contact with authors. Published reports of cohort and case-control studies were considered for inclusion. Pooled estimates were calculated from absolute numbers as weighted mean differences, standard mean differences or odds ratios. Adjusted odds ratios from published reports were also extracted. We identified five case-control and 11 cohort studies. The incidence of foot ulcers ranged from 8% to 17% in the cohort studies, with varying lengths of follow-up. Diagnostic tests and physical signs that detect peripheral neuropathy (biothesiometry, monofilaments and absent ankle reflexes), and those that detect excessive plantar pressure (peak plantar pressure and joint deformity) were all significantly associated with future diabetic foot ulceration. However, there was a paucity of evidence concerning the predictive value of symptoms and signs. Further research is needed to establish the independent factors associated with diabetic foot ulceration, particularly elements from a patient's history and physical examination. PMID- 17277316 TI - Derivation and validation of a clinical index for prediction of rapid progression of kidney dysfunction. AB - BACKGROUND: Chronic kidney disease is common among the elderly, and these patients are at risk of progressive kidney dysfunction. AIM: To develop an index to predict rapid progression of kidney dysfunction. DESIGN: Community-based cohort divided into derivation (n = 6789) and validation (n = 3395) subsets. METHODS: We identified 10 184 subjects aged >/=66 years from computerized laboratory data. Prescription drug data was used to define disease categories and medication exposure, and an index for predicting rapid progression of kidney dysfunction (> or =25% decline in glomerular filtration rate over a 2-year period) was obtained from a logistic regression model in the derivation cohort. The risk score for each subject was calculated by summing the component variables together, which were subsequently categorized into five risk classes. RESULTS: Five predictors of rapid progression were identified: age >75 years, cardiac disease, diabetes mellitus, gout, and use of anti-emetic medications. Rates of rapid progression for risk classes I through V were 8.6%, 10.9%, 13.9%, 15.6%, and 24.1%, respectively, for the derivation cohort, and 8.4%, 11.6%, 15.5%, 17.3%, 21.9%, respectively, for the validation cohort. The risk index distinguished between low and high risk of rapid progression, with a 2.5-fold greater risk for the highest, compared to the lowest, risk decile. DISCUSSION: Readily available clinical data can be used to identify most elderly at risk of rapid progression of kidney dysfunction. This simple index could help clinicians to identify patients at risk, and implement strategies to slow the progression of kidney dysfunction. PMID- 17277317 TI - Life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy. AB - BACKGROUND: Limited data are available on the life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy (HAART). AIM: To provide such an estimate using a semi-parametric projection. DESIGN: Statistical analysis. METHODS: Follow-up data for patients newly diagnosed with HIV infection in Taiwan (HIV/AIDS Cohort) from 1 May 1997 to 30 April 2003 (n = 3351, only 1% are injecting drug users) were analysed using the Kaplan-Meier method. The survival function for an age- and gender-matched reference population was generated by the Monte Carlo method from the life-table of the general population. A constant excess hazard model was used to project long-term survival of HIV-infected patients, with linear extrapolation of a logit transformed curve of survival ratio between HIV-infected patients and the reference population. RESULTS: The 5-year survival rate was 58% in patients who had already developed AIDS at diagnosis (AIDS group), and 89% in those who had not (non-AIDS group). Extrapolation yielded an expected mean survival time of 10.6 years after diagnosis for the AIDS group, and 21.5 years after diagnosis for the non-AIDS group. DISCUSSION: Our results support the expansion of HIV screening programs to minimize delay in diagnosis. With continuing advances in HAART, this estimate of survival in initially asymptomatic patients may be conservative. Their long life expectancy raises questions about what kind of preventive heath services should be offered. These should be addressed through further analysis of overall benefit and cost-effectiveness. PMID- 17277318 TI - The JBS-2 guidelines on prevention of cardiovascular disease in clinical practice: an opportunity missed. PMID- 17277319 TI - A hyperglycaemic hyperosmolar state in a young child: diagnostic insights from a quantitative analysis. AB - This teaching exercise demonstrates how the application of principles of physiology can identify the cause of a severe degree of hyperglycaemia (plasma glucose concentration 80 mmol/l) in a very young patient with newly diagnosed diabetes mellitus, determine whether the patient has diabetic ketoacidosis, and highlight the potential risks for this patient on admission and during initial therapy. A consultation with Professor McCance was sought to determine whether this patient had an unusual degree of 'insulin resistance'. There were also uncertainties regarding the acid-base diagnosis. The patient did not appear to have an important degree of metabolic acidosis as judged from his pH of 7.39 and plasma bicarbonate concentration of 20 mmol/l in arterial blood; hence the diagnostic impression was that he had a hyperglycaemic hyperosmolar state. However, his plasma anion gap was significantly elevated, and remained so for 60 h, despite the administration of insulin. Issues in management concerning the basis for this severe degree of hyperglycaemia and how to minimize the risk of developing cerebral oedema are addressed. The missing links in this interesting story emerge during a discussion between the medical team and their mentor, Professor McCance. PMID- 17277320 TI - IgG4-associated multifocal systemic fibrosis presenting with fever of unknown origin. PMID- 17277321 TI - AIDS and the Black Death. PMID- 17277323 TI - Passing on. PMID- 17277324 TI - Differential trends in alcohol-related mortality: a register-based follow-up study in Finland in 1987-2003. AB - AIMS: To assess to what extent alcohol-related mortality has changed by age, sex and education in Finland in 1987-2003, a period which saw two periods of economic growth, separated by a severe depression (1991-1995). METHODS: A register-based follow-up study of all over 15-year-old Finnish men and women. Age, sex and education of the participants were measured at the time of the 1985, 1990, 1995 and 2000 censuses. Follow-up for mortality was for 1987-2003. The outcome measure was alcohol-related mortality, which was defined using information on the underlying and contributory causes of death. RESULTS: Among men and women aged 45 years and over, the trends in alcohol-related mortality were associated with economic cycles. Among those aged less than 45 years, alcohol-related mortality decreased from the early 1990s, but intoxication-related accidents and violence still contributed largely to premature mortality. The unfavourable trend for older men resulted from an increase in mortality due to directly alcohol attributable diseases, alcohol-related diseases of the circulatory system and accidents and violence, and for older women from an increase due to intoxication related accidents and violence, and alcohol-attributable diseases. Alcohol related mortality was higher in lower educational groups, and among women the educational gap widened towards the end of the study period. CONCLUSIONS: This study shows that trends in both economic conditions and per capita consumption of alcohol are not associated with trends in alcohol-related mortality in all population subgroups. In health policy more attention should be paid to divergent trends in gender, age and education specific alcohol-related mortality. PMID- 17277325 TI - Improvements in extremity dose assessment for ionising radiation medical applications. AB - This study aims at testing the INTE ring dosemeter based on MCP-Ns and TLD-100 detectors on users from the field of medical applications, namely radiopharmacists, personnel at a cyclotron facility with corresponding FDG synthesis cells, interventional radiology technologists and radiologists. These users were chosen due to the fact that they have a significantly high risk of exposure to their hands. Following previous results, MCP-Ns TL thin material was used for radiology measurements, whereas TLD-100 was preferred for other applications. The dosemeters were tested to make sure that they were waterproof and that they could be sterilised properly prior to use. Results confirm the need to implement finger dosimetry, mainly for interventional radiologists as finger dose can be >50 times higher than whole-body dose and 3 times higher than wrist dose. PMID- 17277326 TI - Track structure: time evolution from physics to chemistry. AB - This review discusses interaction cross sections of charged particles (electrons, protons, light ions) with atoms and molecules. The focus is on biological relevant targets like liquid water which serves as a substitute of soft tissue in most Monte Carlo codes. The spatial distribution of energy deposition patterns by different radiation qualities and their importance to the time evolution from the physical to the chemical stage or radiation response is discussed. The determination of inelastic interaction cross sections for charged particles in condensed matter is discussed within the relativistic plane-wave Born approximation and semi-empirical models. The dielectric-response-function of liquid water is discussed. PMID- 17277327 TI - Measurement and simulation of lineal energy distribution at the CERN high energy facility with a tissue equivalent proportional counter. AB - The response of a tissue equivalent proportional counter (TEPC) in a mixed radiation field with a neutron energy distribution similar to the radiation field at commercial flight altitudes has been studied. The measurements have been done at the CERN-EU High-Energy Reference Field (CERF) facility where a well characterised radiation field is available for intercomparison. The TEPC instrument used by the ARC Seibersdorf Research is filled with pure propane gas at low pressure and can be used to determine the lineal energy distribution of the energy deposition in a mass of gas equivalent to a 2 microm diameter volume of unit density tissue, of similar size to the nuclei of biological cells. The linearity of the detector response was checked both in term of dose and dose rate. The effect of dead-time has been corrected. The influence of the detector exposure location and orientation in the radiation field on the dose distribution was also studied as a function of the total dose. The microdosimetric distribution of the absorbed dose as a function of the lineal energy has been obtained and compared with the same distribution simulated with the FLUKA Monte Carlo transport code. The dose equivalent was calculated by folding this distribution with the quality factor as a function of linear energy transfer. The comparison between the measured and simulated distributions show that they are in good agreement. As a result of this study the detector is well characterised, thanks also to the numerical simulations the instrument response is well understood, and it's currently being used onboard the aircrafts to evaluate the dose to aircraft crew caused by cosmic radiation. PMID- 17277328 TI - Calibration and background measurements with a tissue equivalent proportional counter. AB - A tissue-equivalent-proportional counter (TEPC) instrument has been used as the reference instrument for cosmic radiation measurement at flight altitudes by several institutes. For purposes of characterisation the response of the instrument has been investigated under different standard radiation conditions, in terms of radiation particle, energy and angle of incidence. Photon sources and photon beams of energies up to 6.6 MeV and neutron beams up to 200 MeV were used. To have a better understanding of the shielding influence of the instrument assembly, the angle dependence of response was analysed for several radiation conditions. Specific measurement conditions were simulated with the Monte Carlo transport code, FLUKA. The measured instrument response was compared with simulation results. It was demonstrated, that simulations were very helpful to understand the instrument's response. The TEPC instrument used by the Austrian Research Centre Seibersdorf (ARCS) research simulates the energy deposition in a unit density tissue volume of 2 microm diameter, of similar size to a cell nucleus. Pure propane at low pressure is used as measurement gas. To characterise the instrument at low dose rates background measurements were done 800 m below ground and at the ultra low level laboratory in Gran Sasso, 1380 m below ground. These results were compared with measurements on the Earth's surface at different altitudes on mountains up to 3480 m above sea level. The significant increase of the expected dose rate is well reproduced by the experiments at mountain altitudes. As a result of this study a full characterisation and a thorough understanding of the performance and reliability of the detector was achieved. PMID- 17277329 TI - In-flight dose estimates for aircraft crew and pregnant female crew members in military transport missions. AB - Aircraft fighter pilots may experience risks other than the exposure to cosmic radiation due to the characteristics of a typical fighter flight. The combined risks for fighter pilots due to the G-forces, hypobaric hypoxia, cosmic radiation exposure, etc. have determined that pregnant female pilots should remain on ground. However, several military transport missions can be considered an ordinary civil aircraft flight and the question arises whether a pregnant female crew member could still be part of the aircraft crew. The cosmic radiation dose received was estimated for transport missions carried out on the Hercules C-130 type of aircraft by a single air squad in 1 month. The flights departed from Lisboa to areas such as: the Azores, several countries in central and southern Africa, the eastern coast of the USA and the Balkans, and an estimate of the cosmic radiation dose received on each flight was carried out. A monthly average cosmic radiation dose to the aircraft crew was determined and the dose values obtained were discussed in relation to the limits established by the European Union Council Directive 96/29/Euratom. The cosmic radiation dose estimates were performed using the EPCARD v3.2 and the CARI-6 computing codes. EPCARD v3.2 was kindly made available by GSF-National Research Centre for Environment and Health, Institute of Radiation Protection (Neuherberg, Germany). CARI-6 (version July 7, 2004) was downloaded from the web site of the Civil Aerospace Medical Institute, Federal Aviation Administration (USA). In this study an estimate of the cosmic radiation dose received by military aircraft crew on typical transport missions is made. PMID- 17277330 TI - SCOOP: a simple method for identification of novel protein superfamily relationships. AB - MOTIVATION: Profile searches of sequence databases are a sensitive way to detect sequence relationships. Sophisticated profile-profile comparison algorithms that have been recently introduced increase search sensitivity even further. RESULTS: In this article, a simpler approach than profile-profile comparison is presented that has a comparable performance to state-of-the-art tools such as COMPASS, HHsearch and PRC. This approach is called SCOOP (Simple Comparison Of Outputs Program), and is shown to find known relationships between families in the Pfam database as well as detect novel distant relationships between families. Several novel discoveries are presented including the discovery that a domain of unknown function (DUF283) found in Dicer proteins is related to double-stranded RNA binding domains. AVAILABILITY: SCOOP is freely available under a GNU GPL license from http://www.sanger.ac.uk/Users/agb/SCOOP/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 17277331 TI - Disease-specific genomic analysis: identifying the signature of pathologic biology. AB - MOTIVATION: Genomic high-throughput technology generates massive data, providing opportunities to understand countless facets of the functioning genome. It also raises profound issues in identifying data relevant to the biology being studied. RESULTS: We introduce a method for the analysis of pathologic biology that unravels the disease characteristics of high dimensional data. The method, disease-specific genomic analysis (DSGA), is intended to precede standard techniques like clustering or class prediction, and enhance their performance and ability to detect disease. DSGA measures the extent to which the disease deviates from a continuous range of normal phenotypes, and isolates the aberrant component of data. In several microarray cancer datasets, we show that DSGA outperforms standard methods. We then use DSGA to highlight a novel subdivision of an important class of genes in breast cancer, the estrogen receptor (ER) cluster. We also identify new markers distinguishing ductal and lobular breast cancers. Although our examples focus on microarrays, DSGA generalizes to any high dimensional genomic/proteomic data. PMID- 17277332 TI - NetMatch: a Cytoscape plugin for searching biological networks. AB - NetMatch is a Cytoscape plugin which allows searching biological networks for subcomponents matching a given query. Queries may be approximate in the sense that certain parts of the subgraph-query may be left unspecified. To make the query creation process easy, a drawing tool is provided. Cytoscape is a bioinformatics software platform for the visualization and analysis of biological networks. AVAILABILITY: The full package, a tutorial and associated examples are available at the following web sites: http://alpha.dmi.unict.it/~ctnyu/netmatch.html, http://baderlab.org/Software/NetMatch. PMID- 17277333 TI - Automatic correspondence of tags and genes (ACTG): a tool for the analysis of SAGE, MPSS and SBS data. AB - A critical step in any SAGE, MPSS and SBS data analysis is tag-to-gene assignment. Current available tools are limited by a tag-by-tag annotation process and/or do not provide the dataset that is used to produce a complete tag to-gene mapping. We developed ACTG, a web-based application that allows a large scale tag-to-gene mapping using several reference datasets. ACTG can annotate SAGE (14 or 21 bp), MPSS (17 or 20 bp) and SBS (16 bp) data for both human and mouse organisms. AVAILABILITY: http://retina.med.harvard.edu/ACTG/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 17277334 TI - DFprot: a webtool for predicting local chain deformability. AB - DFprot is a web-based server for predicting main-chain deformability from a single protein conformation. The server automatically performs a normal-mode analysis (NMA) of the uploaded structure and calculates its capability to deform at each of its residues. Non-specialists can easily and rapidly obtain a quantitative first approximation of the flexibility of their structures with a simple and efficient interface. AVAILABILITY: http://sbg.cib.csic.es/Software/DFprot. PMID- 17277335 TI - Hardware acceleration of processing of mass spectrometric data for proteomics. AB - MOTIVATION: High-resolution mass spectrometers generate large data files that are complex, noisy and require extensive processing to extract the optimal data from raw spectra. This processing is readily achieved in software and is often embedded in manufacturers' instrument control and data processing environments. However, the speed of this data processing is such that it is usually performed off-line, post data acquisition. We have been exploring strategies that would allow real-time advanced processing of mass spectrometric data, making use of the reconfigurable computing paradigm, which exploits the flexibility and versatility of Field Programmable Gate Arrays (FPGAs). This approach has emerged as a powerful solution for speeding up time-critical algorithms. We describe here a reconfigurable computing solution for processing raw mass spectrometric data generated by MALDI-ToF instruments. The hardware-implemented algorithms for de noising, baseline correction, peak identification and deisotoping, running on a Xilinx Virtex 2 FPGA at 180 MHz, generate a mass fingerprint over 100 times faster than an equivalent algorithm written in C, running on a Dual 3 GHz Xeon workstation. PMID- 17277336 TI - Lean body mass to estimate GFR. PMID- 17277337 TI - Elevation of plasma D-dimer is closely associated with venous thrombosis produced by double-lumen catheter in pre-dialysis patients. AB - BACKGROUND: A double-lumen catheter (DLC) is used as a temporary blood access in emergency haemodialysis and continuous haemodialysis. There are various reports concerning thrombosis related to use of DLC and other catheters. The objective of this study is to assess the incidence of venous thrombosis when using DLC in patients undergoing blood purification. Method. Forty-eight Japanese patients, hospitalized in the Saitama Medical University hospital from December 2004 to April 2005, who had DLC insertion as a temporary blood access for blood purification. The existence of a thrombus was determined using ultrasonography, before catheter insertion, and every 2 days after insertion up to 3 weeks. At the time of DLC insertion, general blood tests including plasma D-dimer, and serum C reactive protein (CRP) were performed. When DLC was removed, plasma D-dimer and serum CRP were measured. RESULTS: In 30 of 48 (62.5%) patients with DLC insertion as a temporary blood access for haemodialysis, venous thrombi with diameters>1.1 mm were detected by venous ultrasonography. No predictive factors were recognized except an increase in plasma D-dimer that was significantly higher in the patients with venous thrombus. The changes in plasma D-dimer were 3.54 (SE 0.8) microg/dl in patient with thrombus, and 0.29 (0.30) microg/dl in patient without thrombus (P=0.004). CONCLUSIONS: The study suggests that changes in plasma D dimer after the insertion of the catheter may be used to predict thrombus formation and is more accurate than baseline measurements, and easier than other new markers. PMID- 17277338 TI - Linear anti-glomerular basement membrane IgG but no glomerular disease: Goodpasture's syndrome restricted to the lung. PMID- 17277339 TI - Implementation of 'K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease' after the introduction of cinacalcet in a population of patients on chronic haemodialysis. AB - BACKGROUND: The purpose of the present study was to evaluate the impact of cinacalcet administration on the attainment of Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (NFK-K/DOQI) targets, in a group of dialysis patients with secondary hyperparathyroidism that were not controlled with vitamin D metabolites due to inadequate elevations in serum calcium and/or phosphorus. METHODS: Twenty-eight patients undergoing haemodialysis that presented secondary hyperparathyroidism (PTH > 300 pg/ml) with difficulty to use vitamin D either because of hypercalcaemia (>10.2 mg/dl) and/or hyperphosphoraemia (>5.5 mg/dl) were included in this study. The follow-up period was 9 months before and after the introduction of cinacalcet. We started by adding 30 mg of cinacalcet orally once daily to their previous vitamin D metabolite treatment. The following variables were calculated and recorded: the mean of all measurements of serum Ca, P and parathyroid hormones (PTH), and Ca x P in each patient; calcium in dialysate (mEq/l); doses of vitamin D administered; doses of cinacalcet used, and the average prescription of calcium-based phosphate binders, sevelamer hydrochloride and aluminum binders, corresponding to two periods according to the introduction of cinacalcet. The proportions of patients with different serum Ca levels as well as serum P levels; serum PTH levels and CaxP at the beginning and at the end of the nine month period of treatment with cinacalcet were calculated. RESULTS: Serum PTH (826.9 +/- 325 vs 248.1 +/- 77.3, P < 0.001), serum calcium (9.9 +/- 0.6 vs 8.6 +/- 0.4, P < 0.001) and the Ca x P product (94.7 +/- 7.3 vs 43.6 +/- 8.5; P < 0.001) diminished significantly whereas serum phosphorus remained unchanged (4.8 +/- 1.5 vs 4.3 +/- 1.1; P = NS). Before cinacalcet, 23 patients had severe hyperparathyroidism (serum PTH > 500) and 15 patients hypercalcaemia (serum calcium >10.2 mg/dl). After 9 months of treatment, all 28 patients showed serum PTH < 500 pg/ml and serum calcium <10.2 mg/dl; 64.7% of the patients achieved Ca, P, Ca x P and PTH objectives simultaneously. While the mean dose of cinacalcet increased along the 9 months of treatment (P < 0.001), there were no significant changes in vitamin D metabolites (P = 0.5), neither in the mean doses of calcium-containing agents, nor in the mean prescribed doses of sevelamer (P < 0.01), and aluminium-containing agents diminished significantly (P < 0.05). CONCLUSIONS: In summary, the combination of cinacalcet and low doses of vitamin D improved significantly the control of PTH and Ca x P in patients with severe secondary hyperparathyroidism on chronic haemodialysis, without adverse effects and with lower doses of phosphate binders. PMID- 17277341 TI - Gastrointestinal stromal tumours (GIST) in kidney transplant recipients--a report of two cases. PMID- 17277340 TI - Thin basement membrane nephropathy cannot be diagnosed reliably in deparaffinized, formalin-fixed tissue. AB - In diagnostic renal pathology, electron microscopy is ideally performed on glutaraldehyde-fixed, plastic resin-embedded tissue (EM-G). When no glomeruli are present in the portion of the biopsy fixed in glutaraldehyde, formalin-fixed, paraffin-embedded tissue can be reprocessed for electron microscopy (EM-F). The usefulness of this salvage technique for the diagnosis of thin basement membrane nephropathy (TBMN) has not been studied systematically. Here we compare the glomerular basement membrane (GBM) thickness by EM-G vs EM-F in 21 renal biopsies, including TBMN (eight patients), normals (two patients), minimal change disease (MCD) (six patients) and diabetic nephropathy (DN) (five patients). There was significant reduction of the GBM thickness by EM-F compared with EM-G across all diagnostic categories in all 21 cases. The mean percentage reduction in GBM thickness was 23% for the TBMN cases, 40% for the normal/MCD cases and 34% for the DN cases. Four patients with MCD had a mean GBM thickness by EM-F that fell below the defining threshold for diagnosis of TBMN. For the TBMN cases, the 99th percentile for GBM thickness by EM-F was 194 nm, suggesting that the diagnosis of TBMN by EM-F can be excluded with confidence if the GBM thickness is above 200 nm. No clear criteria could be established to diagnose TBMN by EM-F. Renal pathologists should be aware that reprocessing of paraffin tissue for EM causes artifactual GBM thinning that precludes accurate diagnosis of TBMN. PMID- 17277342 TI - A novel Cys1638Tyr NC1 domain substitution in alpha5(IV) collagen causes Alport syndrome with late onset renal failure without hearing loss or eye abnormalities. AB - BACKGROUND: Mutations in the type IV collagen gene, COL4A5, are associated with Alport syndrome, characterized by ultrastructural abnormalities of the glomerular basement membrane (GBM), with or without progressive loss of renal function, characteristic ophthalmic signs and/or high tone sensorineural deafness. More than 300 sequence variants in type IV collagen have been identified, including alterations in the non-collagenous NC1 domain. METHODS: We performed linkage analysis and sequencing to identify the mutation in a New Zealand family with Alport glomerulonephritis and late onset renal failure without hearing loss or eye abnormalities. RESULTS: We report a novel c.4913G>A (p.Cys1638Tyr) alteration in the NC1 domain of COL4A5, identified in a moderately large family, eight of whom were confirmed by renal biopsy to have renal abnormalities. Only three of eight mutant male members of the pedigree progressed to end-stage renal failure. The remaining five mutant males exhibit either chronic renal disease at age 36, 46 and 72, or as yet show no renal disease at ages 39 and 39. Extra-renal manifestations such as sensorineural deafness or ocular changes were absent from all family members carrying the mutation. CONCLUSION: This variant is the first reported to affect the tenth of 12 cysteine residues in the NC1 domain. We conclude that the cysteine to tyrosine substitution in the NC1 domain of the alpha5(IV) collagen chain in this family leads to a mild form of Alport syndrome, including absence of extra-renal features. PMID- 17277344 TI - Mouse models for congenital nephrogenic diabetes insipidus: what can we learn from them? PMID- 17277343 TI - Hyperleptinaemia and chronic inflammation after peritonitis predicts poor nutritional status and mortality in patients on peritoneal dialysis. AB - BACKGROUND: The serum leptin level is elevated in patients undergoing peritoneal dialysis (PD) and associated with a loss of lean body mass. The nutritional status of PD patients may further be worsened following peritonitis. We investigated the association between hyperleptinaemia, inflammation and malnourishment in PD-related peritonitis. METHODS: We conducted a prospective study on PD patients who developed peritonitis. Blood samples were obtained as baseline (D0) before the onset of peritonitis, and once peritonitis developed, leptin, adiponectin (ADPN) and other inflammatory markers were collected, on day 1 (D1), day 7 (D7) and day 42 (D42) of peritonitis. Patients were followed-up for any censor event or 1 year after peritonitis. RESULTS: Forty-two patients with a mean age of 62.9+/-13.2 years were recruited. Fourteen (33.3%) were diabetic. The serum leptin levels increased significantly from baseline to day 1 and 7, but fell back to the premorbid state at day 42. In contrast, the ADPN level decreased from a baseline value of 15.60+/-10.4 microg/ml to 13.01+/-8.1 microg/ml on day 1 (P=0.01) but rose to 14.39+/-8.9 microg/ml on day 7 (P=0.28) and 13.87+/-7.9 microg/ml on day 42 (P=0.21). High-sensitivity C-reactive protein (hs-CRP) increased significantly from baseline to day 1, 7 and even at day 42. The lean body mass (LBM) and nutritional markers decreased significantly after peritonitis. For patients with high hs-CRP (>3.0 mg/l) at day 42, there was a higher mortality rate than for those with lower hs-CRP (<3.0 mg/l, P=0.02), even if they were in clinical remission of peritonitis. CONCLUSIONS: Our study confirmed an increase in serum leptin during acute peritonitis and a prolonged course of systemic inflammation after apparent clinical remission of peritonitis. These factors related to the persistent chronic inflammation may contribute to the development of malnourishment and poor survival rate. PMID- 17277345 TI - High incidence of renal failure in patients with aortic aneurysms. AB - BACKGROUND: Renal failure (RF) is a well-recognized complication of aortic aneurysms (AA) although its incidence has been poorly documented previously. The purpose of this study is to examine the incidence of RF in patients with AA and prognosis of AA patients with RF. METHODS: Renal function, complications and prognosis of AA patients with RF were retrospectively reviewed in 350 AA patients (median age 69.8+/-10.7 years) in the International Medical Center of Japan from 1989 to 1999. RESULTS: Among 350 patients with AA, 90 patients (25.7%) had chronic renal failure (CRF) at the initiation of follow-up. The number of CRF patients increased to 117 (33.4%) at 30 months of follow-up. Forty-four out of 160 patients (27.5%) who had aortic surgery developed postoperative acute renal failure (ARF). Stepwise logistic regression analysis revealed that age (>or=65 years), hypertension and multiple aneurysms were independent risk factors for CRF, whereas dissecting aneurysms, preoperative serum creatinine (sCr) levels and duration of surgery were independent risk factors for postoperative ARF in AA patients. In the 5-year follow-up of AA patients with CRF, the mean slopes of 1/serum-creatinine did not significantly differ between conservative treatment and surgical treatment. The survival rates were 49.5% in the conservative treatment group and 67.3% in the surgical treatment group. CONCLUSION: Our data suggest that the management of renal function including blood pressure from an early stage in AA patients is important since CRF is highly prevalent in AA patients and affects their prognosis and mortality. PMID- 17277346 TI - The predictors of central and obstructive sleep apnoea in haemodialysis patients. AB - BACKGROUND: Sleep apnoea (SA) is often observed in haemodialysis patients, but there have been few studies on types of SA and their predictors. We therefore investigated the prevalence and types of SA and the associations between types of SA and clinical factors in haemodialysis patients. METHODS: We initially examined nocturnal oxygen desaturation index (ODI) (desaturation of >4%/events per hour) in 119 haemodialysis patients (68 males, mean age of 61.4 years). Patients with ODI of more than five were diagnosed as having SA. Then, 30 patients underwent polysomnography and we measured Apnoea-hypopnoea index (AHI), which was calculated as the number of apnoeas plus hypopnoeas per hour of sleep. Clinical characteristics were examined in all patients. RESULTS: Forty-one (34.5%) of the 119 patients had SA. Twenty-seven (22.7%) of the 119 patients had SA with subjective symptoms such as daytime somnolence and snoring. There was a significant difference between body mass index (BMI) in patients with SA and that in patients without SA (22.5 vs 19.8 kg/m2, P<0.001). There were significantly higher prevalences of hypertension (85.4 vs 66.7%, P<0.05) and diabetes mellitus (36.6 vs 10.3%, P<0.01) in patients with SA than those in patients without SA. Multivariable analysis showed that BMI was independently associated with the occurrence of SA (OR 1.20, 95% CI 1.05-1.38). Mean AHI of 30 patients who underwent polysomnography was 53.2+/-28.9 [central apnoea, 4.1+/-5.6 (8%); obstructive apnoea, 21.7+/-21.5 (42%); mixed apnoea, 4.9+/-8.0 (9%); hypopnoea, 21.4+/-15.5 (41%)]. The number of obstructive apnoea events per hour was significantly correlated with BUN (r=0.490, P<0.01), Cr (r=0.418, P<0.05) and BMI (r=0.489, P<0.01) and was inversely correlated with serum bicarbonate (r=-0.646, P<0.01) and brain natriuretic peptide (BNP) (r=-0.481, P<0.01). The number of central apnoea events per hour was correlated inversely with PaO2 (r=-0.393, P<0.05) and PaCO2 (r=-0.388, P<0.05) and tended to be correlated with cardiothoracic ratio (CTR) (r=0.347, P=0.060). CONCLUSIONS: There is a high prevalence of SA in haemodialysis patients. The dominant type of SA in haemodialysis patients is obstructive sleep apnoea (OSA). Uraemia (BUN, Cr), metabolic acidosis (serum bicarbonate) and BMI are good predictors of OSA. PaO2, PaCO2 and CTR are good predictors of central sleep apnoea (CSA). Good management of these factors might improve SA in haemodialysis patients. PMID- 17277347 TI - A German family with glucocorticoid-remediable aldosteronism. AB - BACKGROUND: The prevalence of primary hyperaldosteronism (PHA) in the hypertensive population has increased in recent years. Glucocorticoid-remediable aldosteronism (GRA) is a rare monogenic form of PHA. Here we report a German family with GRA. Since the phenotype of GRA varies widely, we asked whether recommended algorithms for PHA diagnosis distinguish GRA from other forms of PHA. METHODS: Plasma aldosterone (pg/ml) and renin (pg/ml) levels were determined in three hypertensive family members with GRA before and after sodium loading with 2 l of saline (0.9%), during posture and after 1 week of 2 mg dexamethasone daily. 24 h blood pressure and urinary excretion of aldosterone, cortisol precursors and metabolites were measured before and after dexamethasone. Southern blot hybridization and long-range PCR were performed to identify the chimeric gene. RESULTS: All three affected patients had normal potassium levels but markedly increased aldosterone/renin ratios of 472, 213 and >322 (normal range<50) indicating PHA. Sodium loading failed to lower plasma aldosterone below the threshold of 50 pg/ml in all patients. During posture, aldosterone increased in one but decreased in both other GRA patients. Elevated 18-hydroxycortisol, free aldosterone and its main metabolite aldosterone-18-glucuronid and tetrahydroaldosterone returned to normal range after 1 week dexamethasone in all patients, but blood pressure was reduced only in one patient. The chimeric gene was identified in affected family members by Southern blot and PCR. CONCLUSIONS: The aldosterone/renin ratio is a valid screening and sodium loading a valid confirmation test in GRA. Determination of elevated urinary excretion of specific aldosterone metabolites and identification of the chimeric gene are mandatory since a lacking blood pressure response to dexamethasone can be misleading. PMID- 17277348 TI - Right ventricular hypertrophy and diastolic dysfunction in arterial switch patients without pulmonary artery stenosis. AB - OBJECTIVE: To assess pulmonary flow dynamics and right ventricular (RV) function in patients without significant anatomical narrowing of the pulmonary arteries late after the arterial switch operation (ASO) by using magnetic resonance imaging (MRI). METHODS: 17 patients (mean (SD), 16.5 (3.6) years after ASO) and 17 matched healthy subjects were included. MRI was used to assess flow across the pulmonary trunk, RV systolic and diastolic function, and RV mass. RESULTS: Increased peak flow velocity (>1.5 m/s) was found across the pulmonary trunk in 14 of 17 patients. Increased RV mass was found in ASO patients: 14.9 (3.4) vs 10.0 (2.6) g/m2 in normal subjects (p<0.01). Delayed RV relaxation was found after ASO: mean tricuspid valve E/A peak flow velocity ratio = 1.60 (0.96) vs 1.92 (0.61) in normal subjects (p = 0.03), and E-deceleration gradients = -1.69 (0.73) vs -2.66 (0.96) (p<0.01). After ASO, RV mass correlated with pulmonary trunk peak flow velocity (r = 0.49, p<0.01) and tricuspid valve E-deceleration gradients (r = 0.35, p = 0.04). RV systolic function was well preserved in patients (ejection fraction = 53 (7)% vs 52 (8)% in normal subjects, p = 0.72). CONCLUSIONS: Increased peak flow velocity in the pulmonary trunk was often observed late after ASO, even in the absence of significant pulmonary artery stenosis. Haemodynamic consequences were RV hypertrophy and RV relaxation abnormalities as early markers of disease, while systolic RV function was well preserved. PMID- 17277349 TI - Intensive statin therapy in acute coronary syndromes and stable coronary heart disease: a comparative meta-analysis of randomised controlled trials. AB - BACKGROUND: Intensive statin therapy reduces major adverse cardiovascular events (MACE), but the effect on mortality is unclear. OBJECTIVE: To determine whether intensive statin therapy reduces all-cause mortality compared with moderate statin therapy in patients with recent acute coronary syndromes (ACS) and stable coronary heart disease (CHD). METHODS: Medline, Embase, the Cochrane Database, the internet, and conference proceedings from 1966 to 2006 were searched to identify relevant trials. Selection criteria were randomised allocation to intensive statin therapy (atorvastatin 80 mg/day, simvastatin 80 mg/day, or rosuvastatin 20-40 mg/day) versus moderate statin therapy, recent ACS or stable CHD at the time of randomisation, and > or =6 months of follow-up. RESULTS: Six trials, encompassing 110 271 patient-years, were pooled. In patients with recent ACS, intensive statin therapy reduced all-cause mortality from 4.6% to 3.5% over 2.0 years (OR = 0.75, 95% CI 0.61 to 0.93). In patients with stable CHD, intensive statin therapy had no effect on all-cause mortality over 4.7 years (OR = 0.99, 95% CI 0.89 to 1.11). Overall, intensive statin therapy was associated with a reduction in MACE (OR = 0.84, 95% CI 0.77 to 0.91) and admissions to hospital for heart failure (OR = 0.72, 95% CI 0.62 to 0.83). Intensive statin therapy was also associated with an increase in hepatic transaminases >3 times normal (OR = 3.73, 95% CI 2.11 to 6.58) and a trend towards increased creatine kinase >10 times normal and/or rhabdomyolysis (OR = 1.96, 95% CI 0.50 to 7.63). CONCLUSIONS: Compared with moderate statin therapy, intensive statin therapy reduces all-cause mortality in patients with recent ACS but not in patients with stable CHD. PMID- 17277351 TI - The interaction of interventricular pacing intervals and left ventricular lead position during temporary biventricular pacing evaluated by tissue Doppler imaging. AB - OBJECTIVE: To determine the effects of interventricular pacing interval and left ventricular (LV) pacing site on ventricular dyssynchrony and function at baseline and during biventricular pacing, using tissue Doppler imaging. METHODS: Using an angioplasty wire to pace the left ventricle, 20 patients with heart failure and left bundle branch block underwent temporary biventricular pacing from lateral (n = 20) and inferior (n = 10) LV sites at five interventricular pacing intervals: +80, +40, synchronous, -40, and -80 ms. RESULTS: LV ejection fraction (EF) increased (mean (SD) from 18 (8)% to 26 (10)% (p = 0.016) and global mechanical dyssynchrony decreased from 187 (91) ms to 97 (63) ms (p = 0.0004) with synchronous biventricular pacing compared to unpaced baseline. Sequential pacing with LV preactivation produced incremental improvements in EF and global mechanical dyssynchrony (p<0.0001 and p = 0.0026, respectively), primarily as a result of reductions in inter-LV-RV dyssynchrony (p = 0.0001) rather than intra LV dyssynchrony (NS). Results of biventricular pacing from an inferior or lateral LV site were comparable (for example, synchronous biventricular pacing, global mechanical dyssynchrony: lateral LV site, 97 (63) ms; inferior LV site, 104 (41) ms (NS); EF: lateral LV site, 26 (10)%; inferior LV site, 27 (10)% (NS)). ECG morphology was identical during biventricular pacing through an angioplasty wire and a permanent lead. CONCLUSIONS: Sequential biventricular pacing with LV preactivation most often optimises LV synchrony and EF. An inferior LV site offers a good alternative to a lateral site. Pacing through an angioplasty wire may be useful in assessing the acute effects of pacing. PMID- 17277350 TI - Assessing the effectiveness of primary angioplasty compared with thrombolysis and its relationship to time delay: a Bayesian evidence synthesis. AB - BACKGROUND: Meta-analyses of trials have shown greater benefits from angioplasty than thrombolysis after an acute myocardial infarction, but the time delay in initiating angioplasty needs to be considered. OBJECTIVE: To extend earlier meta analyses by considering 1- and 6-month outcome data for both forms of reperfusion. To use Bayesian statistical methods to quantify the uncertainty associated with the estimated relationships. METHODS: A systematic review and meta-analysis published in 2003 was updated. Data on key clinical outcomes and the difference between time-to-balloon and time-to-needle were independently extracted by two researchers. Bayesian statistical methods were used to synthesise evidence despite differences between reported follow-up times and outcomes. Outcomes are presented as absolute probabilities of specific events and odds ratios (ORs; with 95% credible intervals (CrI)) as a function of the additional time delay associated with angioplasty. RESULTS: 22 studies were included in the meta-analysis, with 3760 and 3758 patients randomised to primary angioplasty and thrombolysis, respectively. The mean (SE) angioplasty-related time delay (over and above time to thrombolysis) was 54.3 (2.2) minutes. For this delay, mean event probabilities were lower for primary angioplasty for all outcomes. Mortality within 1 month was 4.5% after angioplasty and 6.4% after thrombolysis (OR = 0.68 (95% CrI 0.46 to 1.01)). For non-fatal reinfarction, OR = 0.32 (95% CrI 0.20 to 0.51); for non-fatal stroke OR = 0.24 (95% CrI 0.11 to 0.50). For all outcomes, the benefit of angioplasty decreased with longer delay from initiation. CONCLUSIONS: The benefit of primary angioplasty, over thrombolysis, depends on the former's additional time delay. For delays of 30-90 minutes, angioplasty is superior for 1-month fatal and non-fatal outcomes. For delays of around 90 minutes thrombolysis may be the preferred option as assessed by 6-month mortality; there is considerable uncertainty for longer time delays. PMID- 17277352 TI - Circulating endothelial progenitor cells and clinical outcome in patients with congestive heart failure. AB - BACKGROUND: Circulating endothelial progenitor cells (EPCs) are increased in conditions associated with ischaemia and can potentially support angiogenesis and vasculogenesis. EPC levels were also shown to predict outcome in patients with atherosclerotic vascular disease. We tested the hypothesis that circulating EPC can predict outcome in patients with congestive heart failure (CHF). METHODS: EPC colony-forming units were measured in the peripheral blood of 107 consecutive patients with CHF with New York Heart Association (NYHA) functional class II-IV. Serum levels of vascular endothelial growth factor (VEGF), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and high-sensitivity C-reactive protein (hsCRP) were also measured. End points were defined as CHF-related hospital admissions and all-cause mortality. RESULTS: Age (p = 0.01), diabetes mellitus (p = 0.002) and EPC levels (p = 0.02) were found to be independent predictors of all-cause mortality. EPC levels did not predict CHF-related hospitalisations. EPC levels correlated positively with NYHA (p = 0.05, r = 0.19), but did not correlate with VEGF, NT-pro-BNP or hsCRP. EPC levels did not differ by the aetiology of CHF. CONCLUSIONS: EPC levels are independent predictors of all-cause mortality among patients with CHF. PMID- 17277353 TI - A national survey of the prevalence, incidence, primary care burden and treatment of atrial fibrillation in Scotland. AB - OBJECTIVE: To examine the epidemiology, primary care burden and treatment of atrial fibrillation (AF). DESIGN: Cross-sectional data from primary care practices participating in the Scottish Continuous Morbidity Recording scheme between April 2001 and March 2002. SETTING: 55 primary care practices (362 155 patients). PARTICIPANTS: 3135 patients with AF. RESULTS: The prevalence of AF in Scotland was 9.4/1000 in men and 7.9/1000 in women (p<0.001) and increased with age (to 71/1000 in individuals aged >85 years). The prevalence of AF decreased with increasing socioeconomic deprivation (9.2/1000 least deprived and 7.5/1000 most deprived category, p = 0.02 for trend). 71% of patients with AF received rate-controlling medication: beta-blocker 28%, rate-limiting calcium-channel blocker 42% and digoxin 43%. 42% of patients received warfarin, 44% received aspirin and 78% received more than one of these. Multivariable analysis showed that men and women aged > or =75 years were more likely (than those aged <75 years) to be prescribed digoxin (men OR 1.41, 95% CI 1.14 to 1.74; women OR 1.88, 95% CI 1.50 to 2.37) and aspirin (2.04, 1.66 to 2.51; 1.79, 1.42 to 2.25) and less likely to receive an antiarrhythmic drug (0.62, 0.48 to 0.81; 0.52, 0.39 to 0.70) or warfarin (0.74, 0.60 to 0.91; 0.58, 0.46 to 0.73). Adjusted analysis showed no socioeconomic gradient in prescribing. CONCLUSIONS: AF is a common condition, more so in men than in women. Deprived individuals are less likely to have AF, a finding raising concerns about socioeconomic gradients in detection and prognosis. Recommended treatments for AF were underused in women and older people. This is of particular concern, given the current trends in population demographics and the evidence that both groups are at higher risk of stroke. PMID- 17277354 TI - Vascular disease in a population-based cohort of individuals hospitalised with coeliac disease. AB - OBJECTIVES: To evaluate the risk of cardiovascular disease in individuals with coeliac disease (CD). DESIGN: Swedish national hospital-based register data were used to identify 13,358 individuals who had been diagnosed with CD (1964-2003) and 64,118 age-matched and sex-matched individuals without CD. Cox regression was used to estimate the risk of vascular disease in subjects with CD. Analyses were restricted to individuals with a follow-up of >1 year and with no vascular disease before study entry. RESULTS: CD was associated with myocardial infarction (HR 1.27; 95% CI 1.09 to 1.48), angina pectoris (1.46; 1.25 to 1.70), heart failure (1.41; 1.22 to 1.62), brain haemorrhage (1.40; 1.05 to 1.88) and ischaemic stroke (1.35; 1.14 to 1.60). These risk estimates were similar when analyses were restricted to adults in whom vascular disease had been listed as the main diagnosis. In post-hoc analyses, where reference individuals were restricted to inpatients, no association was found between CD and later vascular disease, except for a lower risk of heart failure (0.79; 0.68 to 0.92). CONCLUSIONS: The positive association between CD and later vascular disease may be explained by ascertainment bias. PMID- 17277355 TI - Effects of triacylglycerol and diacylglycerol oils on blood clearance, tissue uptake, and hepatic apolipoprotein B secretion in mice. AB - Prior studies have suggested that FAs liberated in the small intestine from ingested 1,3-diacylglycerol (DAG) are inefficiently incorporated into triglyceride (TG) in enterocytes, with less chylomicron TG entering the circulation postprandially. We found less TG, but more monacylglyerol and DAG, with similar total acylglycerol in newly secreted chylomicrons after oral DAG or triacylglycerol (TAG). However, clearance of DAG-chylomicrons was more rapid than that of TAG-chylomicrons; this was associated with more efficient in vitro LPL mediated lipolysis of DAG-derived chylomicrons. Intravenously infused DAG was also cleared faster than TAG in normal mice, via both LPL-mediated lipolysis and apolipoprotein E (apoE)-dependent hepatic uptake. Infusions of TAG, but not DAG, increased plasma TG levels. Greater delivery of DAG-derived FA to the liver during infusion of DAG led to greater TG secretion versus TAG; this allowed the maintenance of similar hepatic TG levels after DAG and TAG infusions. Of note, apoB secretion was similar after DAG versus TAG, indicating the assembly of larger very low density lipoproteins after DAG. In conclusion, reduced plasma TG levels, after oral or intravenous DAG, result from more efficient clearance of DAG by both LPL lipolysis and apoE-mediated hepatic endocytosis. DAG emulsions may by useful for intravenous nutrition in people with preexisting hypertriglyceridemia. PMID- 17277356 TI - Glycogen synthase kinase-3 represses cyclic AMP response element-binding protein (CREB)-targeted immediate early genes in quiescent cells. AB - Despite its central role in cell survival and proliferation, the transcriptional program controlled by GSK-3 is poorly understood. We have employed a systems level approach to characterize gene regulation downstream of PI 3-kinase/Akt/GSK 3 signaling in response to growth factor stimulation of quiescent cells. Of 31 immediate-early genes whose induction was dependent on PI 3-kinase signaling, 12 were induced directly by inhibition of GSK-3. Most of the GSK-3-regulated genes encoded transcription factors, growth factors, and signaling molecules. Binding sites for CREB were highly over-represented in the upstream regions of these genes, with 9 genes containing CREB sites that were conserved in mouse orthologs. Binding sites predicted in 6 genes were confirmed by CREB chromatin immunoprecipitation and forskolin induction of CBP binding. Moreover, CREB siRNA substantially blocked induction of 5 genes by forskolin and of 3 genes following inhibition of GSK-3. These results indicate that GSK-3 actively represses gene expression in quiescent cells, with inhibition of CREB playing a key role in this transcriptional response. PMID- 17277357 TI - Interaction of potassium cyanide with the [Ni-4Fe-5S] active site cluster of CO dehydrogenase from Carboxydothermus hydrogenoformans. AB - The Ni-Fe carbon monoxide (CO) dehydrogenase II (CODHII(Ch)) from the anaerobic CO-utilizing hydrogenogenic bacterium Carboxydothermus hydrogenoformans catalyzes the oxidation of CO, presumably at the Ni-(micro(2)S)-Fe1 subsite of the [Ni-4S 5S] cluster in the active site. The CO oxidation mechanism proposed on the basis of several CODHII(Ch) crystal structures involved the apical binding of CO at the nickel ion and the activation of water at the Fe1 ion of the cluster. To understand how CO interacts with the active site, we have studied the reactivity of the cluster with potassium cyanide and analyzed the resulting type of nickel coordination by x-ray absorption spectroscopy. Cyanide acts as a competitive inhibitor of reduced CODHII(Ch) with respect to the substrate CO and is therefore expected to mimic the substrate. It inhibits the enzyme reversibly, forming a nickel cyanide. In this reaction, one of the four square-planar sulfur ligands of nickel is replaced by the carbon atom of cyanide, suggesting removal of the micro(2)S from the Ni-(micro(2)S)-Fe1 subsite. Upon reactivation of the inhibited enzyme, cyanide is released, and the square-planar coordination of nickel by 4S ligands is recovered, which includes the reformation of the Ni-(micro(2)S)-Fe1 bridge. The results are summarized in a model of the CO oxidation mechanism at the [Ni-4Fe-5S] active site cluster of CODHII(Ch) from C. hydrogenoformans. PMID- 17277358 TI - Diversity in mating behavior of hermaphroditic and male-female Caenorhabditis nematodes. AB - In this study, we addressed why Caenorhabditis elegans males are inefficient at fertilizing their hermaphrodites. During copulation, hermaphrodites generally move away from males before they become impregnated. C. elegans hermaphrodites reproduce by internal self-fertilization, so that copulation with males is not required for species propagation. The hermaphroditic mode of reproduction could potentially relax selection for genes that optimize male mating behavior. We examined males from hermaphroditic and gonochoristic (male-female copulation) Caenorhabditis species to determine if they use different sensory and motor mechanisms to control their mating behavior. Instead, we found through laser ablation analysis and behavioral observations that hermaphroditic C. briggsae and gonochoristic C. remanei and Caenorhabditis species 4, PB2801 males produce a factor that immobilizes females during copulation. This factor also stimulates the vulval slit to widen, so that the male copulatory spicules can easily insert. C. elegans and C. briggsae hermaphrodites are not affected by this factor. We suggest that sensory and motor execution of mating behavior have not significantly changed among males of different Caenorhabditis species; however, during the evolution of internal self-fertilization, hermaphrodites have lost the ability to respond to the male soporific-inducing factor. PMID- 17277359 TI - The flamenco locus controls the gypsy and ZAM retroviruses and is required for Drosophila oogenesis. AB - In Drosophila, the as yet uncloned heterochromatic locus flamenco (flam) controls mobilization of the endogenous retrovirus gypsy through the repeat-associated small interfering (rasi) RNA silencing pathway. Restrictive alleles (flamR) downregulate accumulation of gypsy transcripts in the somatic follicular epithelium of the ovary. In contrast, permissive alleles (flamP) are unable to repress gypsy. DIP1, the closest transcription unit to a flam-insertional mutation, was considered as a good candidate to be a gypsy regulator, since it encodes a dsRNA-binding protein. To further characterize the locus we analyzed P induced flam mutants and generated new mutations by transposon mobilization. We show that flam is required somatically for morphogenesis of the follicular epithelium, the tissue where gypsy is repressed. This developmental activity is necessary to control gypsy and another retroelement, ZAM. We also show that flam is not DIP1, as none of the new permissive mutants affect the DIP1 coding sequence. In addition, two deletions removing DIP1 coding sequences do not affect any of the flamenco functions. Our results suggest that flamenco extends proximally to DIP1, spanning >130 kb of transposon-rich heterochromatin. We propose a model explaining the multiple functions of this large heterochromatic locus. PMID- 17277360 TI - Unusual pattern of nucleotide sequence variation at the OS-E and OS-F genomic regions of Drosophila simulans. AB - Nucleotide variation at the genomic region encompassing the odorant-binding protein genes OS-E and OS-F (OS region) was surveyed in two populations of Drosophila simulans, one from Europe and the other from Africa. We found that the European population shows an atypical and large haplotype structure, which extends throughout the approximately 5-kb surveyed genomic region. This structure is depicted by two major haplotype groups segregating at intermediate frequency in the sample, one haplogroup with nearly no variation, and the other at levels more typical for this species. This pattern of variation was incompatible with neutral predictions for a population at a stationary equilibrium. Nevertheless, neutrality tests contrasting polymorphism and divergence data fail to detect any departure from the standard neutral model in this species, whereas they confirm the non-neutral behavior previously observed at the OS-E gene in D. melanogaster. Although positive Darwinian selection may have been responsible for the observed unusual nucleotide variation structure, coalescent simulation results do not allow rejecting the hypothesis that the pattern was generated by a recent bottleneck in the history of European populations of D. simulans. PMID- 17277361 TI - Prospects for association mapping in classical inbred mouse strains. AB - The collection of classical inbred mouse strains displays heritable variation in a large number of complex traits. Many generations of historical recombination have contributed to the panel of classical strain genomes, raising the possibility that quantitative trait loci could be located with high resolution by correlating strain genotypes and phenotypes. Although this association mapping framework has been successful in several empirical applications, its expected performance remains unclear. We used computer simulations based on a publicly available, dense single-nucleotide polymorphism (SNP) map to measure the power and false-positive rate of association mapping on a genomic scale across 30 commonly used classical inbred strains. Expected power is (i) often low for phenotypic effect sizes that are realistic for complex traits, (ii) highly variable across the genome, and (iii) correlated with linkage disequilibrium, aspects of the allele frequency distribution, and haplotype characteristics, as predicted by theory. Simulations also demonstrate clear potential for spurious associations to be generated by unequal relatedness among the strains. These findings suggest that association mapping in the classical strains is best applied in combination with other procedures, such as QTL mapping. PMID- 17277362 TI - Brc1-mediated rescue of Smc5/6 deficiency: requirement for multiple nucleases and a novel Rad18 function. AB - Smc5/6 is a structural maintenance of chromosomes complex, related to the cohesin and condensin complexes. Recent studies implicate Smc5/6 as being essential for homologous recombination. Each gene is essential, but hypomorphic alleles are defective in the repair of a diverse array of lesions. A particular allele of smc6 (smc6-74) is suppressed by overexpression of Brc1, a six-BRCT domain protein that is required for DNA repair during S-phase. This suppression requires the postreplication repair (PRR) protein Rhp18 and the structure-specific endonucleases Slx1/4 and Mus81/Eme1. However, we show here that the contribution of Rhp18 is via a novel pathway that is independent of PCNA ubiquitination and PRR. Moreover, we identify Exo1 as an additional nuclease required for Brc1 mediated suppression of smc6-74, independent of mismatch repair. Further, the Apn2 endonuclease is required for the viability of smc6 mutants without extrinsic DNA damage, although this is not due to a defect in base excision repair. Several nucleotide excision repair genes are similarly shown to ensure viability of smc6 mutants. The requirement for excision factors for the viability of smc6 mutants is consistent with an inability to respond to spontaneous lesions by Smc5/6 dependent recombination. PMID- 17277363 TI - The nonmuscle myosin phosphatase PP1beta (flapwing) negatively regulates Jun N terminal kinase in wing imaginal discs of Drosophila. AB - Drosophila flapwing (flw) codes for serine/threonine protein phosphatase type 1beta (PP1beta). Regulation of nonmuscle myosin activity is the single essential flw function that is nonredundant with the three closely related PP1alpha genes. Flw is thought to dephosphorylate the nonmuscle myosin regulatory light chain, Spaghetti Squash (Sqh); this inactivates the nonmuscle myosin heavy chain, Zipper (Zip). Thus, strong flw mutants lead to hyperphosphorylation of Sqh and hyperactivation of nonmuscle myosin activity. Here, we show genetically that a Jun N-terminal kinase (JNK) mutant suppresses the semilethality of a strong flw allele. Alleles of the JNK phosphatase puckered (puc) genetically enhance the weak allele flw1, leading to severe wing defects. Introducing a mutant of the nonmuscle myosin-binding subunit (Mbs) further enhances this genetic interaction to lethality. We show that puc expression is upregulated in wing imaginal discs mutant for flw1 and pucA251 and that this upregulation is modified by JNK and Zip. The level of phosphorylated (active) JNK is elevated in flw1 enhanced by puc. Together, we show that disruption of nonmuscle myosin activates JNK and puc expression in wing imaginal discs. PMID- 17277364 TI - The genetics of hybrid male sterility between the allopatric species pair Drosophila persimilis and D. pseudoobscura bogotana: dominant sterility alleles in collinear autosomal regions. AB - F(1) hybrid male sterility is thought to result from interactions between loci on the X chromosome and dominant-acting loci on the autosomes. While X-linked loci that contribute to hybrid male sterility have been precisely localized in many animal taxa, their dominant autosomal interactors have been more difficult to localize precisely and/or have been shown to be of relatively smaller effect. Here, we identified and mapped at least four dominant autosomal factors contributing to hybrid male sterility in the allopatric species pair Drosophila persimilis and D. pseudoobscura bogotana. Using these results, we tested predictions of reduced recombination models of speciation. Consistent with these models, three of the four QTL associated with hybrid male sterility occur in collinear (uninverted) regions of these genomes. Furthermore, these QTL do not contribute significantly to hybrid male sterility in crosses between the sympatric species D. persimilis and D. pseudoobscura pseudoobscura. The autosomal loci identified in this study provide the basis for introgression mapping and, ultimately, for molecular cloning of interacting genes that contribute to F(1) hybrid sterility. PMID- 17277365 TI - How repeatable are associations between polymorphisms in achaete-scute and bristle number variation in Drosophila? AB - Currently, the relevance of common genetic variants--particularly those significantly associated with phenotypic variation in laboratory studies--to standing phenotypic variation in the wild is poorly understood. To address this, we quantified the relationship between achaete-scute complex (ASC) polymorphisms and Drosophila bristle number phenotypes in several new population samples. MC22 is a biallelic, nonrepetitive-length polymorphism 97 bp downstream of the scute transcript. It has been previously shown to be associated with sternopleural bristle number variation in both sexes in a set of isogenic lines. We replicated this association in a large cohort of wild-caught Drosophila melanogaster. We also detected a significant association at MC22 in an outbred population maintained under laboratory conditions for approximately 25 years, but the phenotypic effects in this sample were opposite from the direction estimated in the initial study. Finally, no significant associations were detected in a second large wild-caught cohort or in a set of 134 nearly isogenic lines. Our ability to repeat the initial association in wild samples suggests that it was not spurious. Nevertheless, inconsistent results from the other three panels suggest that the relationship between polymorphic genetic markers and loci contributing to continuous variation is not a simple one. PMID- 17277367 TI - Genomewide analysis of epistatic effects for quantitative traits in barley. AB - The doubled-haploid (DH) barley population (Harrington x TR306) developed by the North American Barley Genome Mapping Project (NABGMP) for QTL mapping consisted of 145 lines and 127 markers covering a total genome length of 1270 cM. These DH lines were evaluated in approximately 25 environments for seven quantitative traits: heading, height, kernel weight, lodging, maturity, test weight, and yield. We applied an empirical Bayes method that simultaneously estimates 127 main effects for all markers and 127(127-1)/2=8001 interaction effects for all marker pairs in a single model. We found that the largest main-effect QTL (single marker) and the largest epistatic effect (single pair of markers) explained approximately 18 and 2.6% of the phenotypic variance, respectively. On average, the sum of all significant main effects and the sum of all significant epistatic effects contributed 35 and 6% of the total phenotypic variance, respectively. Epistasis seems to be negligible for all the seven traits. We also found that whether two loci interact does not depend on whether or not the loci have individual main effects. This invalidates the common practice of epistatic analysis in which epistatic effects are estimated only for pairs of loci of which both have main effects. PMID- 17277368 TI - Evolutionary framework for protein sequence evolution and gene pleiotropy. AB - In this article, we develop an evolutionary model for protein sequence evolution. Gene pleiotropy is characterized by K distinct but correlated components (molecular phenotypes) that affect the organismal fitness. These K molecular phenotypes are under stabilizing selection with microadaptation (SM) due to random optima shifts, the SM model. Random coding mutations generate a correlated distribution of K molecular phenotypes. Under this SM model, we further develop a statistical method to estimate the "effective" number of molecular phenotypes (K(e)) of the gene. Therefore, for the first time we can empirically evaluate gene pleiotropy from the protein sequence analysis. Case studies of vertebrate proteins indicate that K(e) is typically approximately 6-9. We demonstrate that the newly developed SM model of protein evolution may provide a basis for exploring genomic evolution and correlations. PMID- 17277366 TI - Evolution of the male-determining gene SRY within the cat family Felidae. AB - In most placental mammals, SRY is a single-copy gene located on the Y chromosome and is the trigger for male sex determination during embryonic development. Here, we present comparative genomic analyses of SRY (705 bp) along with the adjacent noncoding 5' flank (997 bp) and 3' flank (948 bp) in 36 species of the cat family Felidae. Phylogenetic analyses indicate that the noncoding genomic flanks and SRY closely track species divergence. However, several inconsistencies are observed in SRY. Overall, the gene exhibits purifying selection to maintain function (omega = 0.815) yet SRY is under positive selection in two of the eight felid lineages. SRY has low numbers of nucleotide substitutions, yet most encode amino acid changes between species, and four different species have significantly altered SRY due to insertion/deletions. Moreover, fixation of nonsynonymous substitutions between sister taxa is not consistent and may occur rapidly, as in the case of domestic cat, or not at all over long periods of time, as observed within the Panthera lineage. The former resembles positive selection during speciation, and the latter purifying selection to maintain function. Thus, SRY evolution in cats likely reflects the different phylogeographic histories, selection pressures, and patterns of speciation in modern felids. PMID- 17277369 TI - Power and precision of alternate methods for linkage disequilibrium mapping of quantitative trait loci. AB - Linkage disequilibrium (LD) analysis in outbred populations uses historical recombinations to detect and fine map quantitative trait loci (QTL). Our objective was to evaluate the effect of various factors on power and precision of QTL detection and to compare LD mapping methods on the basis of regression and identity by descent (IBD) in populations of limited effective population size (N(e)). An 11-cM region with 6-38 segregating single-nucleotide polymorphisms (SNPs) and a central QTL was simulated. After 100 generations of random mating with N(e) of 50, 100, or 200, SNP genotypes and phenotypes were generated on 200, 500, or 1000 individuals with the QTL explaining 2 or 5% of phenotypic variance. To detect and map the QTL, phenotypes were regressed on genotypes or (assumed known) haplotypes, in comparison with the IBD method. Power and precision to detect QTL increased with sample size, marker density, and QTL effect. Power decreased with N(e), but precision was affected little by N(e). Single-marker regression had similar or greater power and precision than other regression models, and was comparable to the IBD method. Thus, for rapid initial screening of samples of adequate size in populations in which drift is the primary force that has created LD, QTL can be detected and mapped by regression on SNP genotypes without recovering haplotypes. PMID- 17277370 TI - A balance between two nuclear localization sequences and a nuclear export sequence governs extradenticle subcellular localization. AB - During animal development, transcription factor activities are modulated by several means, including subcellular localization. The Hox cofactor Extradenticle (Exd) has a dynamic subcellular localization, such that Exd is cytoplasmic by default, but is nuclear when complexed with another homeodomain protein, Homothorax (Hth). These observations raise the question of whether dimerization with Hth simply induces Exd's nuclear localization or, alternatively, if Hth is also necessary for Exd activity. To address this question, we analyzed the nuclear transport signals in Exd, including a divergent nuclear export signal (NES) and two nuclear localization signals (NLSs). We show that, although these signals are weak compared to canonical signals, they balance each other in Exd. We also provide evidence that Exd contains an NLS mask that contributes to its cytoplasmic localization. With these signals characterized, we generated forms of Exd that are nuclear localized in the absence of Hth. Surprisingly, although these Exd forms are functional, they do not phenocopy Hth overexpression. These findings suggest that Hth is required for Exd activity, not simply for inducing its nuclear localization. PMID- 17277372 TI - Test of genetical isochronism for longitudinal samples of DNA sequences. AB - Longitudinal samples of DNA sequences, the DNA sequences sampled from the same population at different time points, have increasingly been used to study the evolutionary process of fast-evolving organisms, e.g., RNA virus, in recent years. We propose in this article several methods for testing genetical isochronism or detecting significant genetical heterochronism in this type of sample. These methods can be used to determine the necessary sample size and sampling interval in experimental design or to combine genetically isochronic samples for better data analysis. We investigate the properties of these test statistics, including their powers of detecting heterochronism, assuming different evolutionary processes using simulation. The possible choices and usages of these test statistics are discussed. PMID- 17277371 TI - The evolution of sex and recombination in response to abiotic or coevolutionary fluctuations in epistasis. AB - Evolutionary biologists have identified several factors that could explain the widespread phenomena of sex and recombination. One hypothesis is that host parasite interactions favor sex and recombination because they favor the production of rare genotypes. A problem with many of the early models of this so called Red Queen hypothesis is that several factors are acting together: directional selection, fluctuating epistasis, and drift. It is thus difficult to identify what exactly is selecting for sex in these models. Is one factor more important than the others or is it the synergistic action of these different factors that really matters? Here we focus on the analysis of a simple model with a single mechanism that might select for sex: fluctuating epistasis. We first analyze the evolution of sex and recombination when the temporal fluctuations are driven by the abiotic environment. We then analyze the evolution of sex and recombination in a two-species coevolutionary model, where directional selection is absent (allele frequencies remain fixed) and temporal variation in epistasis is induced by coevolution with the antagonist species. In both cases we contrast situations with weak and strong selection and derive the evolutionarily stable (ES) recombination rate. The ES recombination rate is most sensitive to the period of the cycles, which in turn depends on the strength of epistasis. In particular, more virulent parasites cause more rapid cycles and consequently increase the ES recombination rate of the host. Although the ES strategy is maximized at an intermediate period, some recombination is favored even when fluctuations are very slow. By contrast, the amplitude of the cycles has no effect on the ES level of sex and recombination, unless sex and recombination are costly, in which case higher-amplitude cycles allow the evolution of higher rates of sex and recombination. In the coevolutionary model, the amount of recombination in the interacting species also has a large effect on the ES, with evolution favoring higher rates of sex and recombination than in the interacting species. In general, the ES recombination rate is less than or equal to the recombination rate that would maximize mean fitness. We also discuss the effect of migration when sex and recombination evolve in a metapopulation. We find that intermediate parasite migration rates maximize the degree of local adaptation of the parasite and lead to a higher ES recombination rate in the host. PMID- 17277373 TI - Rampant gene exchange across a strong reproductive barrier between the annual sunflowers, Helianthus annuus and H. petiolaris. AB - Plant species may remain morphologically distinct despite gene exchange with congeners, yet little is known about the genomewide pattern of introgression among species. Here we analyze the effects of persistent gene flow on genomic differentiation between the sympatric sunflower species Helianthus annuus and H. petiolaris. While the species are strongly isolated in testcrosses, genetic distances at 108 microsatellite loci and 14 sequenced genes are highly variable and much lower (on average) than for more closely related but historically allopatric congeners. Our analyses failed to detect a positive association between levels of genetic differentiation and chromosomal rearrangements (as reported in a prior publication) or proximity to QTL for morphological differences or hybrid sterility. However, a significant increase in differentiation was observed for markers within 5 cM of chromosomal breakpoints. Together, these results suggest that islands of differentiation between these two species are small, except in areas of low recombination. Furthermore, only microsatellites associated with ESTs were identified as outlier loci in tests for selection, which might indicate that the ESTs themselves are the targets of selection rather than linked genes (or that coding regions are not randomly distributed). In general, these results indicate that even strong and genetically complex reproductive barriers cannot prevent widespread introgression. PMID- 17277374 TI - Genetic mapping in the presence of genotyping errors. AB - Genetic maps are built using the genotypes of many related individuals. Genotyping errors in these data sets can distort genetic maps, especially by inflating the distances. We have extended the traditional likelihood model used for genetic mapping to include the possibility of genotyping errors. Each individual marker is assigned an error rate, which is inferred from the data, just as the genetic distances are. We have developed a software package, called TMAP, which uses this model to find maximum-likelihood maps for phase-known pedigrees. We have tested our methods using a data set in Vitis and on simulated data and confirmed that our method dramatically reduces the inflationary effect caused by increasing the number of markers and leads to more accurate orders. PMID- 17277375 TI - Prediction of breeding values and selection responses with genetic heterogeneity of environmental variance. AB - There is empirical evidence that genotypes differ not only in mean, but also in environmental variance of the traits they affect. Genetic heterogeneity of environmental variance may indicate genetic differences in environmental sensitivity. The aim of this study was to develop a general framework for prediction of breeding values and selection responses in mean and environmental variance with genetic heterogeneity of environmental variance. Both means and environmental variances were treated as heritable traits. Breeding values and selection responses were predicted with little bias using linear, quadratic, and cubic regression on individual phenotype or using linear regression on the mean and within-family variance of a group of relatives. A measure of heritability was proposed for environmental variance to standardize results in the literature and to facilitate comparisons to "conventional" traits. Genetic heterogeneity of environmental variance can be considered as a trait with a low heritability. Although a large amount of information is necessary to accurately estimate breeding values for environmental variance, response in environmental variance can be substantial, even with mass selection. The methods developed allow use of the well-known selection index framework to evaluate breeding strategies and effects of natural selection that simultaneously change the mean and the variance. PMID- 17277376 TI - Role of the mod(mdg4) common region in homolog segregation in Drosophila male meiosis. AB - Homologous chromosomes must pair and establish stable connections during prophase I of meiosis to segregate reliably from each other at anaphase I. In most organisms, the stable connections, called chiasmata, arise from crossovers. In Drosophila males, homologs pair and segregate without crossing over. Chiasmata are replaced by a homolog conjunction complex that includes the Stromalin in Meiosis (SNM) and Modifier of Mdg4 in Meiosis (MNM) proteins. MNM is one of 31 alternative splice products of mod(mdg4), all of which share a common 402-amino acid N terminus and differ at their C termini. Previous data demonstrated that an MNM-specific exon is required for homolog conjunction, but did not address whether the N-terminal common region, which includes a BTB domain that can mediate coalescence of protein-DNA complexes, is also required. Here we describe a mutation in the common region of mod(mdg4), Z3-3401, that causes qualitatively similar phenotypes as the MNM-specific alleles but disrupts X-Y segregation much more drastically than autosomal segregation. The mutant MNM protein in Z3-3401 is expressed throughout prophase I in spermatocytes but the protein is confined to the cytoplasm, suggesting that the Z3-3401 mutation disrupts a signal required for nuclear localization or retention. Z3-3401 fails to complement a large battery of lethal and semilethal alleles in the common region for meiotic nondisjunction, including an allele containing an amino acid substitution at a conserved residue in the BTB/POZ domain, consistent with a general requirement for the mod(mdg4) common region in homolog segregation. PMID- 17277377 TI - nup154 genetically interacts with cup and plays a cell-type-specific function during Drosophila melanogaster egg-chamber development. AB - Nucleoporin Nup154 is a Drosophila component of the nuclear pore complex (NPC), evolutionarily conserved from yeast to humans. While functional studies carried out in both yeast and metazoan cells indicated that Nup154 homologs are key elements of the NPC framework, the striking phenotypic specificity displayed by nup154 hypomorphic mutant alleles suggested that Nup154 might play additional roles in the context of the NPC. Actually, genetic analyses demonstrated that mutant nurse-cell nuclei do not undergo a normal chromosome dispersal process, uncovering an essential requirement for nup154 gene function during oogenesis. In this report, we show that Nup154 interacts genetically and physically with Cup, a germline-specific protein implicated in multiple aspects of female gametogenesis, including the regulation of the nurse-cell chromosome structure. The two proteins colocalize in vivo and are co-immunoprecipitated from ovarian extracts. Moreover, cup, nup154 double mutants exhibit much stronger oogenesis defects than single mutants. Our findings delineate an intriguing scenario where an ubiquitous nucleoporin might directly influence specialized developmental events. PMID- 17277379 TI - Differential gene expression of Caenorhabditis elegans grown on unmethylated sterols or 4alpha-methylsterols. AB - Transcriptional profiles of Caenorhabditis elegans grown on unmethylated sterols (desMSs) or on 4alpha-methylsterols (4MSs) were compared using microarrays. Thirty-four genes were upregulated and 2 were downregulated>2-fold by growth on 4MSs, including 13 cuticle collagen (col) genes, 1 cuticulin gene (cut-1), 2 groundhog-like (grl) genes, and 1 groundhog gene (grd-4); col-36 and grl-20 were increased 12- and 19-fold, respectively. Fifteen of these 17 genes have been assigned to metabolic mountain 17, suggesting coordinate 4MS-mediated regulation of expression. Quantitative RT-PCR was performed on 27-51 h old animals grown on cholesterol (a desMS) or lophenol (a 4MS). col-36 and grl-20 showed similar cyclic peaks of expression in cholesterol and similar alterations in lophenol, suggesting coregulation. Of six additional grl genes, only grl-3 was upregulated on lophenol; the rest were downregulated. Cyclicity of expression was lost or altered in all six. Nuclear receptor genes nhr-23, nhr-25, nhr-41, and daf-12 all showed cyclic expression in cholesterol and significant downregulation in lophenol by RT-PCR. Expression of the insulin-like receptor daf-2 was lower in lophenol, whereas that of its major downstream target daf-16 was higher. Thus, major changes in gene expression accompany growth on 4MSs, but with surprisingly little effect on normal growth and development. PMID- 17277378 TI - Novel mad2 alleles isolated in a Schizosaccharomyces pombe gamma-tubulin mutant are defective in metaphase arrest activity, but remain functional for chromosome stability in unperturbed mitosis. AB - A previously isolated fission yeast gamma-tubulin mutant containing apparently stabilized microtubules proliferated at an approximately identical rate as wild type, yet the mutant mitosis spindle dynamics were aberrant, particularly the kinetochore microtubule dynamics. Progression through mitosis in the mutant, however, resulted in mostly accurate chromosome segregation. In the absence of the spindle assembly checkpoint gene, mad2+, the spindle dynamics in the gamma tubulin mutant were greatly compromised, leading to a high incidence of chromosome missegregation. Unlike in wild-type cells, green fluorescent protein (GFP)-tagged Mad2 protein often accumulated near one of the poles of an elongating spindle in the gamma-tubulin mutant. We isolated novel mad2 mutants that were defective in arresting mitotic progression upon gross perturbation of the spindle formation but remained functional for the viability of the gamma tubulin mutant. Further, the mad2 mutations did not appreciably destabilize minichromosomes in unperturbed mitoses. When overexpressed ectopically, these mutant Mad2 proteins sequestered wild-type Mad2, preventing its function in mitotic checkpoint arrest, but not in minichromosome stability. These results indicated that the Mad2 functions required for checkpoint arrest and chromosome stability in unperturbed mitosis are genetically discernible. Immunoprecipitation studies demonstrated that GFP-fused mutant Mad2 proteins formed a Mad1-containing complex with altered stability compared to that formed with wild-type Mad2, providing clues to the novel mad2 mutant phenotype. PMID- 17277380 TI - Docosahexaenoic acid synthesis from alpha-linolenic acid by rat brain is unaffected by dietary n-3 PUFA deprivation. AB - Rates of conversion of alpha-linolenic acid (alpha-LNA, 18:3n-3) to docosahexaenoic acid (DHA, 22:6n-3) by the mammalian brain and the brain's ability to upregulate these rates during dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) are unknown. To answer these questions, we measured conversion coefficients and rates in post-weaning rats fed an n-3 PUFA deficient (0.2% alpha-LNA of total fatty acids, no DHA) or adequate (4.6% alpha LNA, no DHA) diet for 15 weeks. Unanesthetized rats in each group were infused intravenously with [1-(14)C]alpha-LNA, and their arterial plasma and microwaved brains collected at 5 minutes were analyzed. The deficient compared with adequate diet reduced brain DHA by 37% and increased brain arachidonic (20:4n-6) and docosapentaenoic (22:5n-6) acids. Only 1% of plasma [1-(14)C]alpha-LNA entering brain was converted to DHA with the adequate diet, and conversion coefficients of alpha-LNA to DHA were unchanged by the deficient diet. In summary, the brain's ability to synthesize DHA from alpha-LNA is very low and is not altered by n-3 PUFA deprivation. Because the liver's reported ability is much higher, and can be upregulated by the deficient diet, DHA converted by the liver from circulating alphaLNA is the source of the brain's DHA when DHA is not in the diet. PMID- 17277381 TI - Monounsaturated fatty acyl-coenzyme A is predictive of atherosclerosis in human apoB-100 transgenic, LDLr-/- mice. AB - ACAT2, the enzyme responsible for the formation of cholesteryl esters incorporated into apolipoprotein B-containing lipoproteins by the small intestine and liver, forms predominantly cholesteryl oleate from acyl-CoA and free cholesterol. The accumulation of cholesteryl oleate in plasma lipoproteins has been found to be predictive of atherosclerosis. Accordingly, a method was developed in which fatty acyl-CoA subspecies could be extracted from mouse liver and quantified. Analyses were performed on liver tissue from mice fed one of four diets enriched with one particular type of dietary fatty acid: saturated, monounsaturated, n-3 polyunsaturated, or n-6 polyunsaturated. We found that the hepatic fatty acyl-CoA pools reflected the fatty acid composition of the diet fed. The highest percentage of fatty acyl-CoAs across all diet groups was in monoacyl-CoAs, and values were 36% and 46% for the n-3 and n-6 polyunsaturated diet groups and 55% and 62% in the saturated and monounsaturated diet groups, respectively. The percentage of hepatic acyl-CoA as oleoyl-CoA was also highly correlated to liver cholesteryl ester, plasma cholesterol, LDL molecular weight, and atherosclerosis extent. These data suggest that replacing monounsaturated with polyunsaturated fat can benefit coronary heart disease by reducing the availability of oleoyl-CoA in the substrate pool of hepatic ACAT2, thereby reducing cholesteryl oleate secretion and accumulation in plasma lipoproteins. PMID- 17277383 TI - Old wine in new bottle. PMID- 17277382 TI - Electrospray mass spectrometry of human hair wax esters. AB - Wax esters extracted from human hair have been examined by capillary GC-MS and by nano electrospray ionization (ESI) mass spectrometry using a tandem quadrupole mass spectrometer. Initially, the wax esters were examined by capillary GC-MS using conventional means, thus revealing an incomplete chromatographic resolution of the complex array of >200 wax esters ranging from 28 to 40 carbons in length, including saturated/straight-chained, unsaturated/straight-chained, saturated/branched, and unsaturated/branched molecular species. ESI of wax esters produced ammonium adduct ions [M+NH4]+, and collisional activation of these ions formed abundant [RCO2H2]+ product ions. Wax esters containing a double bond in the fatty acyl or fatty alcohol portion of the molecule revealed identical behavior, suggesting little influence of the double bond on the ionization process or subsequent decomposition. The wax ester mixture was analyzed by ESI and tandem mass spectrometry using multiple reaction monitoring and neutral loss scanning. The neutral loss experiment [loss of NH3 and CH2=CH-(CH2)nCH3] was particularly effective at rapidly surveying the complex biological mixture, identifying>160 different wax esters that range from 24 to 42 total carbons. PMID- 17277384 TI - The role of pathology and pathologists in the detection and management of cancer. PMID- 17277385 TI - Clinical relevance of intra-operative sentinel lymph node examination in breast cancer management. AB - OBJECTIVES: To determine the sensitivity, accuracy, and clinical relevance of intra-operative examination of sentinel lymph nodes in breast cancer management. DESIGN: Retrospective study. SETTING: Private anatomical pathology practice. PARTICIPANTS: Three hundred breast cancer patients who underwent axillary sentinel lymph node biopsies for intra-operative assessment between January 2004 and March 2006. MAIN OUTCOME MEASURES: Correct identification of metastatic carcinoma in sentinel lymph nodes during intra-operative examination, sparing patient a second surgery. RESULTS: The intra-operative diagnosis of sentinel lymph node biopsies from 300 consecutive patients were compared with the final pathological diagnoses. The final pathology results showed metastatic carcinoma in 74 patients, of whom 63 (85%) were correctly diagnosed during frozen section examination. There was no false-positive case (positive predictive value 100%). The sensitivity for detecting macro- and micro-metastases were 95% and 50%, respectively (P<0.01). The sensitivity for detecting metastases in T1 and T2/above tumours were 72% and 90%, respectively (P<0.05). CONCLUSIONS: Intra operative examination is a reliable and sensitive method for the detection of sentinel lymph node metastasis. Eighty-five percent of the patients with metastatic disease were correctly diagnosed and spared a second operation for axillary dissection. The disadvantage of missing a positive lymph node is by far outweighed by the advantage of a single stage operation in case of a positive diagnosis. The benefit of intra-operative examination was slightly less in patients with smaller tumours. PMID- 17277386 TI - Fine-needle aspiration cytology of thyroid nodules--how well are we doing? AB - OBJECTIVES: To review the accuracy of fine-needle aspiration cytology in diagnosing non-toxic thyroid nodules and determine what factors are predictive of malignancy in patients with indeterminate cytology results. DESIGN: Retrospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Patients with non-toxic thyroid nodules undergoing thyroidectomy from December 1999 to December 2003. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive value of fine-needle aspiration cytology, predictive factors for malignancy in patients with indeterminate fine-needle aspiration cytology results. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of fine-needle aspiration cytology were 54%, 100%, 100%, and 75% respectively. For the 92 patients with fine-needle aspiration cytology reported as 'indeterminate for malignancy', aspiration cytology subgroup (P=0.005) and age (P=0.001) were significant risk factors for diagnosing malignancy. CONCLUSIONS: Fine-needle aspiration cytology has high positive predictive value for thyroid cancer, enabling us to 'rule-in' malignant lesions with confidence. Among those with indeterminate fine-needle aspiration cytology, atypical cell lesions and age greater than 40 years conferred increased risk of malignancy. PMID- 17277387 TI - A study on body weight perception and weight control behaviours among adolescents in Hong Kong. AB - OBJECTIVE: To examine the relationships between body weight perceptions, estimated body mass index, gender, and weight control behaviours. DESIGN: Cross sectional survey. SETTING: Three secondary schools in Hong Kong. PARTICIPANTS: A total of 1132 secondary school forms 1 and 3 students. MAIN OUTCOME MEASURES: The strength of agreement between perceived weight and estimated body mass index, and the association between perceived weight, estimated body mass index, and weight control behaviours. RESULTS: A total of 14% of students were estimated to be overweight or obese. The agreement between actual (estimated) body mass index and perceived weight was poor in females and fair in males (Kappa 0.137 and 0.225, respectively). In females, there was no evidence of a relationship between body mass index and weight control behaviours. However, there was a relationship between perceived weight and weight control behaviours such that females who perceived themselves as overweight were more likely to exercise, restrict caloric intake, self medicate with diet pills, purge, or use laxatives. In males, there was evidence of a relationship between perceived weight, body mass index, and weight control behaviours. Males who perceived themselves as overweight or were overweight, were more likely to exercise or restrict caloric intake. CONCLUSIONS: Body weight perceptions are not in agreement with actual weight in adolescents. This discrepancy is more marked in females who use a variety of weight control behaviours. These behaviours are motivated by perceived weight rather than actual (estimated) body mass index. Overweight adolescents should be encouraged to adopt appropriate weight control behaviours for their health needs. PMID- 17277388 TI - Incidence of neonatal chlamydial conjunctivitis and its association with nasopharyngeal colonisation in a Hong Kong hospital, assessed by polymerase chain reaction. AB - OBJECTIVES: Using polymerase chain reactions, this study aimed to evaluate the incidence of neonatal chlamydial conjunctivitis in our region of Hong Kong and explore any association between such conjunctivitis and nasopharyngeal colonisation with Chlamydia trachomatis. DESIGN: Prospective epidemiological study. SETTING: Regional hospital, Hong Kong. PATIENTS: Consecutive patients with neonatal conjunctivitis presenting to our hospital were recruited from May 2004 to April 2005 inclusive. Both eyes were investigated separately for Chlamydia trachomatis by polymerase chain reaction, direct immunofluorescent assay, and cell culture by two assigned ophthalmologists. Neonates diagnosed to have ocular Chlamydia trachomatis infection were subjected to additional nasopharyngeal investigations. Complete sets of ocular and nasopharyngeal investigations were also undertaken 1 week after oral erythromycin treatment to confirm complete eradication of Chlamydia trachomatis. RESULTS: Of 192 patients with neonatal conjunctivitis, 24 were diagnosed to have chlamydial conjunctivitis. Fifteen of them had nasopharyngeal colonisation with Chlamydia trachomatis. Among the 20 neonatal chlamydial conjunctivitis patients that completed the follow-up study, one suffered treatment failure. None had clinically diagnosed systemic Chlamydia trachomatis infection 3 months after oral erythromycin. CONCLUSIONS: The incidence of neonatal chlamydial conjunctivitis in our region of Hong Kong was 4 in 1000 live births, of whom 63% had nasopharyngeal presence of Chlamydia trachomatis. Owing to the high rate of nasopharyngeal isolation and possibility of treatment failure, post-treatment ocular and nasopharyngeal polymerase chain reaction testing for Chlamydia trachomatis may be considered to confirm complete eradication. PMID- 17277389 TI - Vaginal hysterectomies in patients without uterine prolapse: a local perspective. AB - OBJECTIVE: To review the results of vaginal hysterectomies in patients without uterine prolapse. DESIGN: Retrospective chart review. SETTING: University affiliated hospital, Hong Kong. PATIENTS: Patients who had vaginal hysterectomies in the absence of uterine prolapse, from 1999 to 2005 inclusive. MAIN OUTCOME MEASURES: The number, indications, operative procedures, and complications of such hysterectomies. RESULTS: A total of 94 patients who underwent vaginal hysterectomy fulfilled the inclusion criteria. They accounted for 4.3 to 8.2% of all hysterectomies performed annually for benign diseases in the department, over the inclusive period 2000 to 2004. The incidences of complications, except bladder injuries, were comparable to those reported in other studies. The incidence of vault haematoma decreased as each surgeon's experience increased and more attention was paid to 'bleeders' at the 'four and eight o'clock areas' and more cephalic regions of the vaginal incision. Increased size of the uterus was an important determinant of the risk of complications. CONCLUSIONS: Vaginal hysterectomy is an underutilised approach in Hong Kong. With more experience and better patient selection, complication rates can be further reduced. Further evaluation is suggested for the role of bleeders at 'four and eight o'clock regions' as potential causes of vault haematoma. PMID- 17277390 TI - Management and outcome of antenatally diagnosed congenital cystic adenomatoid malformation of the lung. AB - OBJECTIVE: To review the management and outcome of babies with antenatally diagnosed congenital cystic adenomatoid malformation. DESIGN: Retrospective cohort review. SETTING: Tertiary neonatal care unit at Queen Mary Hospital and antenatal diagnostic centre at Tsan Yuk Hospital. PATIENTS: Consecutive patients with antenatally suspected congenital cystic adenomatoid malformation in their concepti among antenatal patients attending Tsan Yuk Hospital from 1994 to 2002. Twenty-four of 33 cases were referred to Queen Mary Hospital for postnatal management and for whom comprehensive records were available for analysis in 23. INTERVENTIONS: Postnatal interventions in their babies included investigational imaging for congenital cystic adenomatoid malformation and surgery. MAIN OUTCOME MEASURES: Antenatal and postnatal outcome, as well as pathology of the excised lesions. RESULTS: Antenatal outcome: termination of pregnancy in two cases and spontaneous abortion in one; in-utero regression was documented in nine cases and in one hydropic change was apparent. Postnatal outcome: only eight of 20 babies born alive had symptoms in neonatal period. Two developed serious infective complications in infancy, one with documented in-utero regression. Pulmonary parenchymal abnormalities were detected on computed tomography of the thorax in six of seven cases with normal or non-specific chest radiograph findings. Among nine cases with in-utero regression, congenital cystic adenomatoid malformation was confirmed by operative histology in five and abnormal computed tomography findings in three. Fifteen babies underwent surgical excision, one of whom died because of severe pre-existing pulmonary hypoplasia and nine endured minor postoperative complications. A favourable outcome was documented at a mean follow up of 22 months (range, 2 months-7 years). CONCLUSIONS: In-utero regression of congenital cystic adenomatoid malformation on antenatal ultrasound may not represent genuine resolution. Computed tomographic thorax should be considered in all newborns with antenatally diagnosed congenital cystic adenomatoid malformation, and if confirmed early operation before first hospital discharge is recommended. PMID- 17277391 TI - Introducing external cephalic version in a Malaysian setting. AB - OBJECTIVE: To assess the outcome of external cephalic version for routine management of malpresenting foetuses at term. DESIGN: Prospective observational study. SETTING: Tertiary teaching hospital, Malaysia. PATIENTS: From September 2003 to June 2004, a study involving 41 pregnant women with malpresentation at term was undertaken. An external cephalic version protocol was implemented. Data were collected for identifying characteristics associated with success or failure of external cephalic version. MAIN OUTCOME MEASURES: Maternal and foetal outcome measures including success rate of external cephalic version, maternal and foetal complications, and characteristics associated with success or failure; engagement of presenting part, placental location, direction of version, attempts at version, use of intravenous tocolytic agent, eventual mode of delivery, Apgar scores, birth weights, and maternal satisfaction with the procedure. RESULTS: Data were available for 38 women. External cephalic version was successful in 63% of patients; the majority (75%) of whom achieved a vaginal delivery. Multiparity (odds ratio=34.0; 95% confidence interval, 0.67-1730) and high amniotic fluid index (4.9; 1.3-18.2) were associated with successful external cephalic version. Engagement of presenting part (odds ratio=0.0001; 95% confidence interval, 0.00001-0.001) and a need to resort to backward somersault (0.02; 0.00001-0.916) were associated with poor success rates. Emergency caesarean section rate for foetal distress directly resulting from external cephalic version was 8%, but there was no perinatal or maternal adverse outcome. The majority (74%) of women were satisfied with external cephalic version. CONCLUSIONS: External cephalic version has acceptable success rates. Multiparity, liquor volume, engagement of presenting part, and the need for backward somersault were strong predictors of outcome. External cephalic version is relatively safe, simple to learn and perform, and associated with maternal satisfaction. Modern obstetric units should routinely offer the procedure. PMID- 17277392 TI - Update on the treatment of diabetic retinopathy. AB - OBJECTIVES: To describe the classification, clinical features, and evaluation of diabetic retinopathy and to review its conventional as well as most updated management. DATA SOURCES: Literature search of Medline up to October 2006. STUDY SELECTION: Key words for the literature search were 'diabetic', 'retinopathy', 'treatment', 'laser photocoagulation', 'vitrectomy', 'corticosteroid', 'protein kinase C inhibitor', and 'VEGF inhibitor'. DATA EXTRACTION: Original articles, review papers, and book chapters were reviewed. DATA SYNTHESIS: Diabetic retinopathy remains one of the leading causes of blindness worldwide. The duration of diabetes and severity of hyperglycaemia are the major risk factors. It progresses from non-proliferative diabetic retinopathy to proliferative diabetic retinopathy through various stages, and the accurate diagnosis of its stage is important. Strict metabolic control and tight blood pressure control can significantly reduce the risk of developing retinopathy and its progression, but are difficult to achieve in clinical practice. Laser photocoagulation and vitrectomy are effective in preventing severe visual loss from sight-threatening diabetic retinopathy and its complications, but both modalities have potential side-effects. Results from clinical trials for protein kinase C inhibitors, intravitreal steroid injections, anti-vascular endothelial growth factor agents, angiotensin converting enzyme inhibitors, and growth hormone inhibitors are promising. Evidence from past clinical trials does not support a role for anti platelet agents, aldose reductase inhibitors, and advanced glycation end-products inhibitors. CONCLUSION: Strict metabolic control, tight blood pressure control, laser photocoagulation, and vitrectomy remain the conventional management of diabetic retinopathy. Further clinical trials exploring the role of protein kinase C inhibitors, intravitreal steroid, anti-vascular endothelial growth factor agents, angiotensin converting enzyme inhibitors, growth hormone, and other potential therapies for diabetic retinopathy are actively ongoing. In the near future, results from these clinical trials may lead to the introduction of additional treatments and a corresponding reduction in the frequency of visual loss due to diabetic retinopathy. PMID- 17277393 TI - Gastro-intestinal stromal tumours: a review of current management options. AB - Gastro-intestinal stromal tumours are uncommon malignancies of the gastro intestinal tract, accounting for only 0.2% of all gastro-intestinal malignancies, but are the most common of abdominal sarcomas. Classically, they have been considered amenable only to early stage surgical intervention. Recent advances in targeted cancer therapies have led to the development of effective non-surgical treatment options. This article discusses the epidemiology and physiopathology of, as well as treatment options available for, this uncommon disease. PMID- 17277394 TI - Carnitine-acylcarnitine translocase deficiency in three neonates presenting with rapid deterioration and cardiac arrest. AB - We report on three Chinese neonates with carnitine-acylcarnitine translocase deficiency. They presented within the first 48 hours of life. Two neonates were found in cardiac arrest; one of them survived after resuscitation. The third neonate suddenly developed cardiorespiratory insufficiency and succumbed eventually. The clustering of three cases in 5 years suggests that carnitine acylcarnitine translocase deficiency is not rare in our Chinese population. We advocate that investigation for metabolic diseases including carnitine acylcarnitine translocase deficiency should be performed in cases of sudden infant death and unexplained abrupt clinical deterioration in the early neonatal period. Non-ketotic hypoglycaemia is an early clue. The mainstay of initial treatment is glucose infusion at a rate greater than 7 mg/kg/minute, which inhibits beta-oxidation of fatty acids (the defective enzymatic steps in carnitine-acylcarnitine translocase deficiency) and thus prevents the accumulation of toxic long-chain acylcarnitines. PMID- 17277395 TI - Hepatic portal venous gas complicating septic thrombophlebitis of the superior mesenteric vein. AB - Hepatic portal venous gas is a rare radiological finding with a wide spectrum of underlying pathologies. We describe a case of hepatic portal venous gas due to septic thrombophlebitis of the superior mesenteric vein. The clinical management of portomesenteric venous gas and the importance of computed tomography in delineating its underlying causes are discussed. PMID- 17277396 TI - Olanzapine-induced diabetic ketoacidosis in a Chinese man. AB - We present a case report of a 22-year-old Chinese man with schizophrenia and dissocial personality disorder who was normoglycaemic before taking olanzapine. After commencing olanzapine he developed diabetic ketoacidosis and was managed in the intensive care unit of a general hospital. Olanzapine was stopped and replaced by haloperidol 5 mg/day. He was put on a strict 1500 kcal diabetic diet and required insulin injections to maintain a normal blood sugar level despite cessation of olanzapine for 4 months. Doctors prescribing olanzapine should be aware of the risk of diabetes mellitus. Baseline and regular monitoring of body weight, body mass index, and fasting blood glucose are essential to prevent serious consequences. PMID- 17277397 TI - Fahr's disease: a differential diagnosis of frontal lobe syndrome. AB - Fahr's disease refers to a rare syndrome characterised by symmetrical and bilateral intracranial calcification. The basal ganglia are the most common site of involvement and most cases present with extra-pyramidal symptoms. We describe two men with Fahr's diseases who presented with prominent frontal lobe symptoms. The first man presented with frequent uncontrollable bursts of laughter and crying spells. He later developed mild dysarthric speech and choreoathetoid movement. The second man presented with progressive changes in personality and behaviour. In both cases, there were no parkinsonian features. Computed tomographic scans of both patients demonstrated extensive symmetrical calcification over the basal ganglia and dentate nuclei. A repeated imaging scan in the second patient revealed progressive cerebral atrophy but reduction in the calcification. No underlying cause for the bilateral calcification was found. As frontal lobe symptoms are usually inconspicuous in the early stage, the presence of these symptoms might be overlooked in clinical practice when compared with those suffering from prominent movement disorders. PMID- 17277398 TI - Hybrid endovascular operation for ruptured thoracic aortic aneurysm. AB - The rupture of a thoracic aortic aneurysm is a life-threatening emergency. Conventional open surgical repair carries a high mortality and morbidity. We report an elderly patient who suffered from rupture of a proximal descending thoracic aortic aneurysm close to the aortic arch. A hybrid operation consisting of a right-to-left carotid bypass followed by endovascular repair of the descending thoracic aorta was carried out. The patient recovered uneventfully. A hybrid endovascular repair should be considered the treatment of choice for rupture of a thoracic aortic aneurysm near the arch. PMID- 17277399 TI - Peritoneal computed tomography: a diagnostic tool for genital oedema in patients on peritoneal dialysis. PMID- 17277400 TI - Red eyes after a gang-fight. PMID- 17277401 TI - Visiting community pharmacists project. PMID- 17277402 TI - Typhoid osteomyelitis of the spine is not "extremely rare". PMID- 17277403 TI - Dual aetiologies for hyperinsulinaemic hypoglycaemia in one patient. PMID- 17277404 TI - [Sarcoidosis, easy to miss]. PMID- 17277405 TI - [Sarcoidosis in Iceland 1981-2003]. AB - OBJECTIVE: To investigate the incidence of sarcoidosis in Iceland, its clinical manifestations and potential environmental influences. MATERIALS AND METHODS: All histopathological diagnoses of non-necrotizing granulomas generated in Iceland during the period 1981-2003 were reviewed with respect to a diagnosis of sarcoidosis. Further, patients were identified by searching hospital discharge diagnoses at the University Hospital in Reykjavik and the Regional Hospital in Northern Iceland. Only histologically verified cases were included. RESULTS: A total of 235 patients were found with histopathologically proven sarcoidosis. Limited to patients verified by tissue diagnosis, the annual incidence of sarcoidosis is 3,84/100.000/year. The incidence was found to be 2,8/100,000/year during the first half of the investigation period and 5,0/100,000/year during the second. This rate is lower than in other Nordic countries. There were 122 women and 113 men. The mean age at diagnosis was 50,8 years for women and 47,5 for men. The mean age at diagnosis was higher in Iceland than elsewhere. Clinically, respiratory symptoms predominated. Ocular symptoms and erythema nodosum are rare, and life-threatening cardiovascular and neurological manifestations are distinctly unusual. CONCLUSION: The low incidence is undoubtedly due to the strict inclusion criteria in the present study, i.e. only those with a tissue diagnosis were included. We have no explanation as to the higher age at diagnosis in Iceland than elsewhere. Registration of possible environmental factors and clinical evaluation may be improved. PMID- 17277406 TI - [A surgeon's thoughts on academic activity]. PMID- 17277407 TI - [Chronic eosinophilic pneumonia in Iceland: clinical features, epidemiology and review]. AB - OBJECTIVE: The objective of the study was to describe the incidence and clinical features of chronic eosinophilic pneumonia (CEP) in Iceland and review recent literature. MATERIAL AND METHODS: Retrospective study where information was obtained from clinical charts from 1990-2004. Records, imaging studies and histopathology were evaluated. RESULTS: During the study period 10 individuals were diagnosed with CEP, 7 males and 3 females. Mean age was 58 years. None of the patients was a current smoker. The incidence of CEP during the study period was 0.23 per 100,000/year but increased to 0.54 per 100,000/year during the last 5 years of the study period. Clinical symptoms were malaise, cough, dyspnea, sweating and weight loss. Sedimentation rate was 72 mm/h and C-reactive protein (CRP) 125 mg/L. Eight of the ten patients had increase in blood eosinophils. On chest auscultation crackles were heard in seven patients and wheezing in three. Forced vital capacity (FVC) was 75% of predicted value and forced expiratory volume in one second (FEV1) was 73% of predicted. Mean PO2 was 68 mmHg. All the patients had classic diffuse bilateral opacities on chest radiograph that most commonly were peripheral. All patients were treated with corticosteroids and responded well. The average initial dose of Prednisolone was 42.5 mg per day. Seven of the patients relapsed but they all responded well to repeated treatment. CONCLUSIONS: Chronic eosinophilic pneumonia is a rare disorder but it has specific radiologic and histologic features. It is important to think of the disease in patients with diffuse infiltrates that are resistant to antibiotics. CEP responds well to corticosteroids but there is a high relapse rate, which also responds to treatment. PMID- 17277408 TI - [Choroidal haemangioma worsens after laser therapy for skin port-wine nevus and improves with photodynamic therapy in the eye]. AB - A young man with facial port-wine nevus on one side of his face underwent skin laser treatment on his facial lesions and experienced worsening visual acuity from 0.9 to 0.4 and metamorphosis afterwards in the ipsilateral eye. He was found to have a choroidal haemangioma with an exudative retinal detachment. He received photodynamic therapy resulting in resolution of subretinal fluid and shrinkage of the haemangioma. Visual acuity decreased to 0.1 one week following photodynamic treatment, but improved steadily after that. Nine months following the treatment the visual acuity is 0.5 and metamorphosis is absent. PMID- 17277409 TI - Perfect sorting by reversals is not always difficult. AB - We propose new algorithms for computing pairwise rearrangement scenarios that conserve the combinatorial structure of genomes. More precisely, we investigate the problem of sorting signed permutations by reversals without breaking common intervals. We describe a combinatorial framework for this problem that allows us to characterize classes of signed permutations for which one can compute, in polynomial time, a shortest reversal scenario that conserves all common intervals. In particular, we define a class of permutations for which this computation can be done in linear time with a very simple algorithm that does not rely on the classical Hannenhalli-Pevzner theory for sorting by reversals. We apply these methods to the computation of rearrangement scenarios between permutations obtained from 16 synteny blocks of the X chromosomes of the human, mouse, and rat. PMID- 17277410 TI - Ortholog clustering on a multipartite graph. AB - We present a method for automatically extracting groups of orthologous genes from a large set of genomes by a new clustering algorithm on a weighted multipartite graph. The method assigns a score to an arbitrary subset of genes from multiple genomes to assess the orthologous relationships between genes in the subset. This score is computed using sequence similarities between the member genes and the phylogenetic relationship between the corresponding genomes. An ortholog cluster is found as the subset with the highest score, so ortholog clustering is formulated as a combinatorial optimization problem. The algorithm for finding an ortholog cluster runs in time O(absolute value(E) + absolute value(V) log absolute value(V)), where V and E are the sets of vertices and edges, respectively, in the graph. However, if we discretize the similarity scores into a constant number of bins, the runtime improves to O(absolute value(E) + absolute value(V)). The proposed method was applied to seven complete eukaryote genomes on which the manually curated database of eukaryotic ortholog clusters, KOG, is constructed. A comparison of our results with the manually curated ortholog clusters shows that our clusters are well correlated with the existing clusters. PMID- 17277412 TI - Accurate cancer classification using expressions of very few genes. AB - We aim at finding the smallest set of genes that can ensure highly accurate classification of cancers from microarray data by using supervised machine learning algorithms. The significance of finding the minimum gene subsets is three-fold: 1) It greatly reduces the computational burden and "noise" arising from irrelevant genes. In the examples studied in this paper, finding the minimum gene subsets even allows for extraction of simple diagnostic rules which lead to accurate diagnosis without the need for any classifiers. 2) It simplifies gene expression tests to include only a very small number of genes rather than thousands of genes, which can bring down the cost for cancer testing significantly. 3) It calls for further investigation into the possible biological relationship between these small numbers of genes and cancer development and treatment. Our simple yet very effective method involves two steps. In the first step, we choose some important genes using a feature importance ranking scheme. In the second step, we test the classification capability of all simple combinations of those important genes by using a good classifier. For three "small" and "simple" data sets with two, three, and four cancer (sub)types, our approach obtained very high accuracy with only two or three genes. For a "large" and "complex" data set with 14 cancer types, we divided the whole problem into a group of binary classification problems and applied the 2-step approach to each of these binary classification problems. Through this "divide-and-conquer" approach, we obtained accuracy comparable to previously reported results but with only 28 genes rather than 16,063 genes. In general, our method can significantly reduce the number of genes required for highly reliable diagnosis. PMID- 17277414 TI - Multiclass cancer classification using semisupervised ellipsoid ARTMAP and particle swarm optimization with gene expression data. AB - It is crucial for cancer diagnosis and treatment to accurately identify the site of origin of a tumor. With the emergence and rapid advancement of DNA microarray technologies, constructing gene expression profiles for different cancer types has already become a promising means for cancer classification. In addition to research on binary classification such as normal versus tumor samples, which attracts numerous efforts from a variety of disciplines, the discrimination of multiple tumor types is also important. Meanwhile, the selection of genes which are relevant to a certain cancer type not only improves the performance of the classifiers, but also provides molecular insights for treatment and drug development. Here, we use Semisupervised Ellipsoid ARTMAP (ssEAM) for multiclass cancer discrimination and particle swarm optimization for informative gene selection. ssEAM is a neural network architecture rooted in Adaptive Resonance Theory and suitable for classification tasks. ssEAM features fast, stable, and finite learning and creates hyperellipsoidal clusters, inducing complex nonlinear decision boundaries. PSO is an evolutionary algorithm-based technique for global optimization. A discrete binary version of PSO is employed to indicate whether genes are chosen or not. The effectiveness of ssEAM/PSO for multiclass cancer diagnosis is demonstrated by testing it on three publicly available multiple class cancer data sets. ssEAM/PSO achieves competitive performance on all these data sets, with results comparable to or better than those obtained by other classifiers. PMID- 17277411 TI - EMatch: discovery of high resolution structural homologues of protein domains in intermediate resolution cryo-EM maps. AB - Cryo-EM has become an increasingly powerful technique for elucidating the structure, dynamics, and function of large flexible macromolecule assemblies that cannot be determined at atomic resolution. However, due to the relatively low resolution of cryo-EM data, a major challenge is to identify components of complexes appearing in cryo-EM maps. Here, we describe EMatch, a novel integrated approach for recognizing structural homologues of protein domains present in a 6 10 A resolution cryo-EM map and constructing a quasi-atomic structural model of their assembly. The method is highly efficient and has been successfully validated on various simulated data. The strength of the method is demonstrated by a domain assembly of an experimental cryo-EM map of native GroEL at 6 A resolution. PMID- 17277413 TI - Correcting base-assignment errors in repeat regions of shotgun assembly. AB - Accurate base-assignment in repeat regions of a whole genome shotgun assembly is an unsolved problem. Since reads in repeat regions cannot be easily attributed to a unique location in the genome, current assemblers may place these reads arbitrarily. As a result, the base-assignment error rate in repeats is likely to be much higher than that in the rest of the genome. We developed an iterative algorithm, EULER-AIR, that is able to correct base-assignment errors in finished genome sequences in public databases. The Wolbachia genome is among the best finished genomes. Using this genome project as an example, we demonstrated that EULER-AIR can 1) discover and correct base-assignment errors, 2) provide accurate read assignments, 3) utilize finishing reads for accurate base-assignment, and 4) provide guidance for designing finishing experiments. In the genome of Wolbachia, EULER-AIR found 16 positions with ambiguous base-assignment and two positions with erroneous bases. Besides Wolbachia, many other genome sequencing projects have significantly fewer finishing reads and, hence, are likely to contain more base-assignment errors in repeats. We demonstrate that EULER-AIR is a software tool that can be used to find and correct base-assignment errors in a genome assembly project. PMID- 17277416 TI - Accuracy assessment of diploid consensus sequences. AB - If the origins of fragments are known in genome sequencing projects, it is straightforward to reconstruct diploid consensus sequences. In reality, however, this is not true. Although there are proposed methods to reconstruct haplotypes from genome sequencing projects, an accuracy assessment is required to evaluate the confidence of the estimated diploid consensus sequences. In this paper, we define the confidence score of diploid consensus sequences. It requires the calculation of the likelihood of an assembly. To calculate the likelihood, we propose a linear time algorithm with respect to the number of polymorphic sites. The likelihood calculation and confidence score are used for further improvements of haplotype estimation in two directions. One direction is that low-scored phases are disconnected. The other direction is that, instead of using nominal frequency 1/2, the haplotype frequency is estimated to reflect the actual contribution of each haplotype. Our method was evaluated on the simulated data whose polymorphism rate (1.2 percent) was based on Ciona intestinalis. As a result, the high accuracy of our algorithm was indicated: The true positive rate of the haplotype estimation was greater than 97 percent. PMID- 17277415 TI - Predicting protein-protein interactions from protein domains using a set cover approach. AB - One goal of contemporary proteome research is the elucidation of cellular protein interactions. Based on currently available protein-protein interaction and domain data, we introduce a novel method, Maximum Specificity Set Cover (MSSC), for the prediction of protein-protein interactions. In our approach, we map the relationship between interactions of proteins and their corresponding domain architectures to a generalized weighted set cover problem. The application of a greedy algorithm provides sets of domain interactions which explain the presence of protein interactions to the largest degree of specificity. Utilizing domain and protein interaction data of S. cerevisiae, MSSC enables prediction of previously unknown protein interactions, links that are well supported by a high tendency of coexpression and functional homogeneity of the corresponding proteins. Focusing on concrete examples, we show that MSSC reliably predicts protein interactions in well-studied molecular systems, such as the 26S proteasome and RNA polymerase II of S. cerevisiae. We also show that the quality of the predictions is comparable to the Maximum Likelihood Estimation while MSSC is faster. This new algorithm and all data sets used are accessible through a Web portal at http://ppi.cse.nd.edu. PMID- 17277417 TI - Colored de Bruijn graphs and the genome halving problem. AB - Breakpoint graph analysis is a key algorithmic technique in studies of genome rearrangements. However, breakpoint graphs are defined only for genomes without duplicated genes, thus limiting their applications in rearrangement analysis. We discuss a connection between the breakpoint graphs and de Bruijn graphs that leads to a generalization of the notion of breakpoint graph for genomes with duplicated genes. We further use the generalized breakpoint graphs to study the Genome Halving Problem (first introduced and solved by Nadia El-Mabrouk and David Sankoff). The El-Mabrouk-Sankoff algorithm is rather complex, and, in this paper, we present an alternative approach that is based on generalized breakpoint graphs. The generalized breakpoint graphs make the El-Mabrouk-Sankoff result more transparent and promise to be useful in future studies of genome rearrangements. PMID- 17277418 TI - Distorted metrics on trees and phylogenetic forests. AB - We study distorted metrics on binary trees in the context of phylogenetic reconstruction. Given a binary tree T on n leaves with a path metric d, consider the pairwise distances {d(u,v)} between leaves. It is well known that these determine the tree and the d length of all edges. Here, we consider distortions [symbol: see text] of d such that, for all leaves u and v, it holds that absolute value(d(u,v) - [symbol: see text](u,v)) < f/2 if either d(u,v) < M + f/2 or [symbol: see text](u,v) < M + f/2, where d satisfies f < or = d(e) < or = g for all edges e. Given such distortions, we show how to reconstruct in polynomial time a forest T1, ..., Talpha such that the true tree T may be obtained from that forest by adding alpha - 1 edges and alpha - 1 < or = 2(-omega(M/g)) n. Our distorted metric result implies a reconstruction algorithm of phylogenetic forests with a small number of trees from sequences of length logarithmic in the number of species. The reconstruction algorithm is applicable for the general Markov model. Both the distorted metric result and its applications to phylogeny are almost tight. PMID- 17277420 TI - Metabolic flux estimation--a self-adaptive evolutionary algorithm with singular value decomposition. AB - Metabolic flux analysis is important for metabolic system regulation and intracellular pathway identification. A popular approach for intracellular flux estimation involves using 13C tracer experiments to label states that can be measured by nuclear magnetic resonance spectrometry or gas chromatography mass spectrometry. However, the bilinear balance equations derived from 13C tracer experiments and the noisy measurements require a nonlinear optimization approach to obtain the optimal solution. In this paper, the flux quantification problem is formulated as an error-minimization problem with equality and inequality constraints through the 13C balance and stoichiometric equations. The stoichiometric constraints are transformed to a null space by singular value decomposition. Self-adaptive evolutionary algorithms are then introduced for flux quantification. The performance of the evolutionary algorithm is compared with ordinary least squares estimation by the simulation of the central pentose phosphate pathway. The proposed algorithm is also applied to the central metabolism of Corynebacterium glutamicum under lysine-producing conditions. A comparison between the results from the proposed algorithm and data from the literature is given. The complexity of a metabolic system with bidirectional reactions is also investigated by analyzing the fluctuations in the flux estimates when available measurements are varied. PMID- 17277419 TI - DNA deformation energy as an indirect recognition mechanism in protein-DNA interactions. AB - Proteins that bind to specific locations in genomic DNA control many basic cellular functions. Proteins detect their binding sites using both direct and indirect recognition mechanisms. Deformation energy, which models the energy required to bend DNA from its native shape to its shape when bound to a protein, has been shown to be an indirect recognition mechanism for one particular protein, Integration Host Factor (IHF). This work extends the analysis of deformation to two other DNA-binding proteins, CRP and SRF, and two endonucleases, I-CreI and I-PpoI. Known binding sites for all five proteins showed statistically significant differences in mean deformation energy as compared to random sequences. Binding sites for the three DNA-binding proteins and one of the endonucleases had mean deformation energies lower than random sequences. Binding sites for I-PpoI had mean deformation energy higher than random sequences. Classifiers that were trained using the deformation energy at each base pair step showed good cross-validated accuracy when classifying unseen sequences as binders or nonbinders. These results support DNA deformation energy as an indirect recognition mechanism across a wider range of DNA-binding proteins. Deformation energy may also have a predictive capacity for the underlying catalytic mechanism of DNA-binding enzymes. PMID- 17277421 TI - Quartet-based phylogeny reconstruction with answer set programming. AB - In this paper, a new representation is presented for the Maximum Quartet Consistency (MQC) problem, where solving the MQC problem becomes searching for an ultrametric matrix that satisfies a maximum number of given quartet topologies. A number of structural properties of the MQC problem in this new representation are characterized through formulating into answer set programming, a recent powerful logic programming tool for modeling and solving search problems. Using these properties, a number of optimization techniques are proposed to speed up the search process. The experimental results on a number of simulated data sets suggest that the new representation, combined with answer set programming, presents a unique perspective to the MQC problem. PMID- 17277422 TI - On the length of the longest exact position match in a random sequence. AB - A mixed Poisson approximation and a Poisson approximation for the length of the longest exact match of a random sequence across another sequence are provided, where the match is required to start at position 1 in the first sequence. This problem arises when looking for suitable anchors in whole genome alignments. PMID- 17277424 TI - Child rights and protection. PMID- 17277425 TI - Regulating vaccines: can health-economics tools be used profitably? PMID- 17277426 TI - Effect of iron supplementation on physical performance in children and adolescents: systematic review of randomized controlled trials. AB - OBJECTIVE: To evaluate the effect of iron supplementation on physical performance in children (0-18 years) through systematic review of randomised controlled trials (RCTs). DATA SOURCES: Electronic databases, personal files, handsearch of reviews, bibliographies of books, abstracts and proceedings of international conferences. REVIEW METHODS: RCTs with interventions that included oral or parenteral iron supplementation, fortified formula milk, or cereals were evaluated. The physical performance outcomes studied were heart rate, treadmill endurance times, blood lactate, and oxygen consumption. RESULTS: A total of three studies were included, in all of which iron was supplemented in the form of oral medicinal iron. At 5, 6 and 7 miles per hour running speeds, the pooled weighted mean (95% Cl) difference (WMD) in the heart rate (per minute) between the iron and the placebo, following exercise was -7.3 (-19.6, 4.9; p = 0.241), -6.6 (- 19.9, 6.6; p = 0.327), and -8.0 (-19.7, 3.7; p = 0.182), respectively. After excluding the study with nonanemic subjects, the corresponding figures were -13.1 (-23.2, -3.1; p= 0.01), -14.2 (-22.3, -6.1; p = 0.001) and -12.7 (-23.5, 1.9; p = 0.021), respectively. Oxygen consumption, estimated in two studies, showed no significant difference between the treatment groups. Blood lactate levels were estimated in one study only at two different doses of iron, and were significantly lower (p < 0.05) in iron supplemented group in comparison to placebo both before (7.71 and 7.55 mg/dL versus 8.43 mg/dL) and after (14.36 and 14.35 mg/dL versus 16.48 mg/dL) exercise. Treadmill endurance time was significantly better in iron supplemented group when compared with placebo in one study. CONCLUSIONS: Iron supplementation may have a positive effect on the physical performance of children, as evaluated through the post exercise heart rate in anemic subjects, blood lactate levels and treadmill endurance time. In view of the limited data availability, this finding cannot be considered conclusive. PMID- 17277427 TI - Bullying in schools: prevalence and short-term impact. AB - OBJECTIVES: To estimate the prevalence of bullying in school children and to examine its association with common symptoms in childhood. DESIGN: Prospective survey using a pre-tested questionnaire for conducting a semi structured health interview. SETTING: Randomly selected Public and private schools in a rural area. SUBJECTS: Children aged 8-12 years studying in three schools and their parents. RESULTS: Bullying was reported by 157 (31.4%) of the 500 children interviewed. There was no significant difference in the prevalence of bullying amongst boys and girls in co-education schools. However, it was significantly low in schools enrolling girls alone. Teasing and keeping names were the commonest forms noticed. Causing physical hurt was reported bv 25 (16%) students. Only 24 (24%) parents were aware that their children were being bullied. Feeling sad, preferring to stay alone and frequent tearing of clothes were almost exclusively noted in bullied children and bullied children were more likely to report symptoms such as school phobia, vomiting and sleep disturbances. CONCLUSION: Bullying is a common phenomenon amongst school going children. Frequent bullying is associated with certain symptoms and school absenteeism. Healthcare professionals. should be aware of this phenmnenon so that they can diagnose the underlying cause when these symptoms are reported and plan for appropriate interventions. PMID- 17277428 TI - Bone mineral density in beta-thalassemia major and intermedia. AB - OBJECTIVE: This study was conducted to assess bone mineral density (BMD) and bone mineral content (BMC) in patients with thalassemia major and intermedia, and to correlate them with biochemical and hematological profile. DESIGN: 106 thalassemic patients (49 major and 57 intermedia) were scanned by dual energy xray absorptiometry technique for BMD and BMC at lumbar spine and femoral neck. The effects of sex, transfusion/chelation program as well as hemoglobin, calcium, phosphorus, alkaline phosphatase and serum ferritin level were also evaluated on BMD and BMC. RESULTS: Patients with thalassemia major and intermedia, younger than 20 yr, showed lower BMD and BMC in the lumbar region (p < 0.05). Both parameters correlated significantly with hemoglobin level; other biochemical and hematological parameters did not influence BMD and BMC values. CONCLUSION: Bone marrow density is a good index of bone status in patients with Thalassemia and should be done in these patients annually. PMID- 17277429 TI - Effect of feeding type on the efficacy of phototherapy. AB - OBJECTIVE: The objective of this study was to assess the efficacy of phototherapy for nonhemolytic hyperbilirubinemia and rebound bilirubin levels in breast-fed newborns as compared with mixed-fed (breast milk and formula) newborns. STUDY DESIGN/SETTING: Prospective study of effects of feeding type on response to phototherapy in newborns. METHODS: The subjects were 53 full-term healthy newborns with nonhemolytic hyperbilirubinemia [defined as total serum bilirubin 12 mg/dL (205.2 micromol/L) in the first 48 hours of life or 15 mg/dl (256.5 micromol/L), on subsequent days]. Groups were formed according to type of feeding. Group 1 consisted of 28 breast-fed newborns and group 2 consisted of 25 mixed-fed newborns. Phototherapy was terminated when total serum bilirubin concentration fell to 14 mg/dL (< 239.4 micromol/L). Rebound bilirubin measurements were obtained 24 hours after phototherapy ended. RESULTS: The groups were comparable with respect to age at the start of phototherapy. The amount of weight loss (relative to birth weight) recorded at the start of phototherapy was significantly greater in group 1 than in group 2 (8.1+/- 3.9% vs. 5.4+/- 2.6% p = 0.004). The duration of phototherapy was significantly longer in group 1 than in group 2 (38.6+/- 12.6 h vs. 26.8+/- 9.4 h; P < 0.001). The 24-hour rate of decrease in bilirubin concentration in group 2 was significantly higher than that in group 1 [5.4+/- 2.2 mg/dL/d (92.3+/-37.6 micromol/L/d) vs. 4+/- 1.3 mg/dL/d (68.4+/- 22.2 micromol/L/d); p = 0.01]. The overall rate of decrease in bilirubin concentration in group 1 was significantly lower than that in group 2 [0.16+/- 0.05 mg/dL/h (2.73+/- 0.85 micromol/L/h) vs. 0.22+/- 0.09 mg/dL/h (3.76+/- 1.53 micromol/L/h); p = 0.01]. There was no significant difference between the two groups with respect to rebound bilirubin concentration (P = 0.184). CONCLUSION: Phototherapy effectively reduced bilirubin levels in breastfed newborns with hyperbilirubinemia, but these patients show significantly slower response to this treatment than mixed-fed newborns. PMID- 17277430 TI - Limiting authorship in Indian Pediatrics: an initiative to curb gift authorship. AB - Indian Pediatrics limited the number of authorship to 5, 4 and 2 for Brief Reports (BR), Case Reports (CR), and Letters to the Editor (LE), respectively from January 2003, to curb gift authorship. To analyze the impact of this policy, a comparative analysis was conducted for years 2002-2004. Mean (SD) number of authors was comparable for the three categories over 2002-2004 [BR: 4.2(1.7), 3.8(1.4), 3.9(1.5); CR: 3.3(0.8), 3.3(0.8), 3.2(0.8); LE: 2.1(1.3), 1.9(0.9), 1.8(0.5); P > 0.05]. There was a significant reduction in the number of Senior authors during 2003-2004, as compared to 2002 (P > 0.05). The policy resulted in fewer authorship credits for Senior authors. PMID- 17277431 TI - Glanzmann thrombasthenia in a neonate. AB - Glanzmann thrombasthenia is a qualitative platelet function disorder manifested by skin bleeds, epistaxis, gingival bleeding, gastrointestinal hemorrhage, hematuria, hemarthrosis, intracranial hemorrhage and visceral hematomas. We report a six day old newborn presenting with hematuria following suprapubic aspiration, who was diagnosed as Glanzmann thrombasthenia. We believe it to be the youngest case reported in the literature. PMID- 17277432 TI - Deep vein thrombosis with Staphylococcus aureus septicemia. AB - Deep vein thrombosis (DVT) in children is usually associated with inherited or acquired hypercoagulable state, mechanical obstruction, fractures of long bones, central venous catheterization and prolonged immobility. We report DVT in 4 children with culture proven staphylococcal septicemia. One child died, while other three survived with appropriate antibiotics and anticoagulation therapy. PMID- 17277434 TI - Beaus lines. PMID- 17277433 TI - Pericardial tamponade in neonate following migration of a sialastic central venous catheter. AB - Central venous catheters constitute an essential part of most neonatal intensive care units (NICU). However, they are known to be associated with several complications. We here with report a rare lethal complication of pericardial effusion with cardiac tamponade occurred in a term neonate following central venous line. PMID- 17277437 TI - A technique of transporting neonates with gastroschisis. PMID- 17277438 TI - Primary tuberculosis of mandible. PMID- 17277439 TI - Acute renal impairment after oral ibuprofen for medical closure of patent ductus arteriosus. PMID- 17277440 TI - Structure of cyclophilin from Leishmania donovani at 1.97 A resolution. AB - The crystal structure of cyclophilin from Leishmania donovani (LdCyp) has been determined and refined at 1.97 A resolution to a crystallographic R factor of 0.178 (R(free) = 0.197). The structure was solved by molecular replacement using cyclophilin from Trypanosoma cruzi as the search model. LdCyp exhibits complete structural conservation of the cyclosporin-binding site with respect to the homologous human protein, as anticipated from LdCyp-cyclosporin binding studies. Comparisons with other cyclophilins show deviations primarily in the loop regions. The solvent structure encompassing the molecule has also been analyzed in some detail. PMID- 17277441 TI - Structure of rat acidic fibroblast growth factor at 1.4 A resolution. AB - Fibroblast growth factors (FGFs) constitute a family of 22 structurally related heparin-binding polypeptides that are involved in the regulation of cell growth, survival, differentiation and migration. Here, a 1.4 A resolution X-ray structure of rat FGF1 is presented. Two molecules are present in the asymmetric unit of the crystal and they coordinate a total of five sulfate ions. The structures of human, bovine and newt FGF1 have been published previously. Human and rat FGF1 are found to have very similar structures. PMID- 17277443 TI - Crystallization and preliminary X-ray analysis of cryptolepain, a novel glycosylated serine protease from Cryptolepis buchanani. AB - Cryptolepain is a stable glycosylated novel serine protease purified from the latex of the medicinally important plant Cryptolepis buchanani. The molecular weight of the enzyme is 50.5 kDa, as determined by mass spectrometry. The sequence of the first 15 N-terminal resides of the protease showed little homology with those of other plant serine proteases, suggesting it to be structurally unique. Thus, it is of interest to solve the structure of the enzyme in order to better understand its structure-function relationship. X-ray diffraction data were collected from a crystal of cryptolepain and processed to 2.25 A with acceptable statistics. The crystals belong to the orthorhombic space group C222(1), with unit-cell parameters a = 81.78, b = 108.15, c = 119.86 A. The Matthews coefficient was 2.62 A(3) Da(-1) with one molecule in the asymmetric unit. The solvent content was found to be 53%. Structure determination of the enzyme is under way. PMID- 17277442 TI - Crystallization of the archaeal transcription termination factor NusA: a significant decrease in twinning under microgravity conditions. AB - The transcription termination factor NusA from Aeropyrum pernix was crystallized using a counter-diffusion technique in both terrestrial and microgravity environments. Crystallization under microgravity conditions significantly reduced the twinning content (1.0%) compared with terrestrially grown crystals (18.3%) and improved the maximum resolution from 3.0 to 2.29 A, with similar unit-cell parameters. Based on a comparison of the crystal parameters, the effect of microgravity on protein crystallization is discussed. PMID- 17277444 TI - A multi-step strategy to obtain crystals of the dengue virus RNA-dependent RNA polymerase that diffract to high resolution. AB - Dengue virus, a member of the Flaviviridae genus, causes dengue fever, an important emerging disease with several million infections occurring annually for which no effective therapy exists. The viral RNA-dependent RNA polymerase NS5 plays an important role in virus replication and represents an interesting target for the development of specific antiviral compounds. Crystals that diffract to 1.85 A resolution that are suitable for three-dimensional structure determination and thus for a structure-based drug-design program have been obtained using a strategy that included expression screening of naturally occurring serotype variants of the protein, the addition of divalent metal ions and crystal dehydration. PMID- 17277445 TI - Crystallization and preliminary X-ray analysis of Escherichia coli RNase HI-dsRNA complexes. AB - RNase H binds RNA-DNA hybrid and double-stranded RNA (dsRNA) duplexes with similar affinity, but only cleaves the RNA in the former. To potentially gain insight into the conformational origins of substrate recognition by the enzyme from Escherichia coli, cocrystallization experiments were carried out with RNase HI-dsRNA (enzyme-inhibitor) complexes. Crystals were obtained of two complexes containing 9-mer and 10-mer RNA duplexes that diffracted X-rays to 3.5 and 4 A resolution, respectively. PMID- 17277446 TI - Crystallization and preliminary X-ray analysis of MotY, a stator component of the Vibrio alginolyticus polar flagellar motor. AB - The polar flagellum of Vibrio alginolyticus is rotated by the sodium motor. The stator unit of the sodium motor consists of four different proteins: PomA, PomB, MotX and MotY. MotX and MotY, which are unique components of the sodium motor, form the T-ring structure attached to the LP ring in the periplasmic space. MotY has a putative peptidoglycan-binding motif in its C-terminal region and MotX is suggested to interact with PomB. Thus, MotX and MotY are thought to be required for incorporation and stabilization of the PomA/B complex. In this study, mature MotY composed of 272 amino-acid residues and its SeMet derivative were expressed with a C-terminal hexahistidine-tag sequence, purified and crystallized. Native crystals were grown in the hexagonal space group P6(1)22/P6(5)22, with unit-cell parameters a = b = 104.1, c = 132.6 A. SeMet-derivative crystals belonged to the same space group with the same unit-cell parameters as the native crystals. Anomalous difference Patterson maps of the SeMet derivative showed significant peaks in their Harker sections, indicating that the derivatives are suitable for structure determination. PMID- 17277447 TI - Expression, purification, crystallization and preliminary X-ray diffraction analysis of the VP8* sialic acid-binding domain of porcine rotavirus strain OSU. AB - The rotavirus outer capsid spike protein VP4 is utilized in the process of rotavirus attachment to and membrane penetration of host cells. VP4 is cleaved by trypsin into two domains: VP8* and VP5*. The VP8* domain is implicated in initial interaction with sialic acid-containing cell-surface carbohydrates and triggers subsequent virus invasion. The VP8* domain from porcine OSU rotavirus was cloned and expressed in Escherichia coli. Different crystal forms (orthorhombic P2(1)2(1)2(1) and tetragonal P4(1)2(1)2) were harvested from two distinct crystallization conditions. Diffraction data have been collected to 2.65 and 2.2 A resolution and the VP8*(65-224) structure was determined by molecular replacement. PMID- 17277448 TI - Purification, crystallization and preliminary X-ray analysis of the regulatory subunit of aspartate kinase from Thermus thermophilus. AB - Aspartate kinase (AK) from Thermus thermophilus, which catalyzes the first step of threonine and methionine biosynthesis, is regulated via feedback inhibition by the end product threonine. To elucidate the mechanism of regulation of AK, the regulatory subunit (the beta subunit of T. thermophilus AK) was crystallized in the presence of the inhibitor threonine. Diffraction data were collected to 2.15 A at a synchrotron source. The crystal belongs to the cubic space group P4(3)32 or P4(1)32, with unit-cell parameters a = b = c = 141.8 A. PMID- 17277449 TI - Crystallization and preliminary crystallographic analysis of human Atg4B-LC3 complex. AB - The reversible modification of Atg8 with phosphatidylethanolamine (PE) is crucial for autophagy, the bulk degradation process of cytoplasmic components by the vacuolar/lysosomal system. Atg4 is a cysteine protease that is responsible for the processing and deconjugation of Atg8. Human Atg4B (HsAtg4B; a mammalian orthologue of yeast Atg4) and LC3 (a mammalian orthologue of yeast Atg8) were expressed and purified and two complexes, one consisting of HsAtg4B(1-354) and LC3(1-120) (complex I; the product complex) and the other consisting of HsAtg4B(1 354) and LC3(1-124) (complex II; the substrate complex), were crystallized using polyethylene glycol 3350 as a precipitant. In both complexes His280 of HsAtg4B was mutated to alanine. The crystals belong to the same space group P2(1)2(1)2(1), with unit-cell parameters a = 47.5, b = 91.8, c = 102.6 A for complex I and a = 46.9, b = 90.9, c = 102.5 A for complex II. Diffraction data were collected to a resolution of 1.9 A from both crystals. PMID- 17277450 TI - Cloning, expression, purification, crystallization and preliminary X-ray crystallographic study of DHNA synthetase from Geobacillus kaustophilus. AB - The aerobic Gram-positive bacterium Geobacillus kaustophilus is a bacillus species that was isolated from deep-sea sediment from the Mariana Trench. 1,4 Dihydroxy-2-naphthoate (DHNA) synthetase plays a vital role in the biosynthesis of menaquinone (vitamin K(2)) in this bacterium. DHNA synthetase from Geobacillus kaustophilus was crystallized in the orthorhombic space group C222(1), with unit cell parameters a = 77.01, b = 130.66, c = 131.69 A. The crystal diffracted to a resolution of 2.2 A. Preliminary studies and molecular-replacement calculations reveal the presence of three monomers in the asymmetric unit. PMID- 17277451 TI - Crystallization and X-ray diffraction analysis of the beta-ketoacyl-acyl carrier protein reductase FabG from Aquifex aeolicus VF5. AB - The gene product of fabG from Aquifex aeolicus has been heterologously expressed in Escherichia coli. Purification of the protein took place using anion-exchange and size-exclusion chromatography and the protein was then crystallized. Diffraction data were collected to a maximum resolution of 1.8 A and the initial phases were determined by molecular replacement. The A. aeolicus FabG protein is a putative beta-ketoacyl-acyl carrier protein reductase. Structure-function studies of this protein are being performed as part of a larger project investigating naturally occurring deviations from highly conserved residues within the short-chain oxidoreductase (SCOR) family. PMID- 17277452 TI - Crystallization and X-ray diffraction analysis of the DNA-remodelling protein DnaD from Bacillus subtilis. AB - The DnaD protein is an essential component of the chromosome-replication machinery of the Gram-positive bacterium Bacillus subtilis and is part of the primosomal cascade that ultimately loads the replicative ring helicase DnaC onto DNA. Moreover, DnaD is a global regulator of DNA architecture, as it forms higher order nucleoprotein structures in order to open supercoiled DNA. Here, the crystallization and preliminary X-ray diffraction analysis of the two domains of DnaD from B. subtilis are reported. Crystals of the N-terminal domain are trigonal, with either P3(1)21 or P3(2)21 space-group symmetry, and diffracted X rays to 2.0 A resolution; crystals of the C-terminal domain are hexagonal, with space group P6(1) or P6(5), and diffracted X-rays to 2.9 A resolution in-house. Determination of the structure of the DnaD domains will provide insight into how remodelling of the nucleoid is associated with priming of replication in the model Gram-positive organism B. subtilis. PMID- 17277453 TI - Purification, crystallization and preliminary X-ray analysis of Hsp33 from Saccharomyces cerevisiae. AB - The heat-shock protein Hsp33 from the yeast Saccharomyces cerevisiae has been overexpressed, purified and crystallized. A crystal was obtained using the hanging-drop vapour-diffusion method and a data set was collected to 2.7 A resolution. The crystal belongs to space group P4(3)2(1)2, with unit-cell parameters a = b = 96.43, c = 132.22 A, alpha = beta = gamma = 90 degrees . The asymmetric unit is assumed to contain two subunits of Hsp33, with a V(M) value of 2.96 A(3) Da(-1) and a solvent content of 58.41%. PMID- 17277454 TI - Crystallization and preliminary X-ray diffraction analysis of omega-amino acid:pyruvate transaminase from Chromobacterium violaceum. AB - The enzyme omega-transaminase catalyses the conversion of chiral omega-amines to ketones. The recombinant enzyme from Chromobacterium violaceum has been purified to homogeneity. The enzyme was crystallized from PEG 4000 using the microbatch method. Data were collected to 1.7 A resolution from a crystal belonging to the triclinic space group P1, with unit-cell parameters a = 58.9, b = 61.9, c = 63.9 A, alpha = 71.9, beta = 87.0, gamma = 74.6 degrees . Data were also collected to 1.95 A from a second triclinic crystal form. The structure has been solved using the molecular-replacement method. PMID- 17277455 TI - Crystallization and preliminary crystallographic analysis of DtsR1, a carboxyltransferase subunit of acetyl-CoA carboxylase from Corynebacterium glutamicum. AB - DtsR1, a carboxyltransferase subunit of acetyl-CoA carboxylase derived from Corynebacterium glutamicum, was crystallized by the sitting-drop vapour-diffusion method using polyethylene glycol 6000 as a precipitant. The crystal belongs to the trigonal system with space group R32 and contains three subunits in the asymmetric unit. A molecular-replacement solution was found using the structure of transcarboxylase 12S from Propionibacterium shermanii as a search model. PMID- 17277456 TI - Purification, crystallization and preliminary X-ray diffraction studies of D tagatose 3-epimerase from Pseudomonas cichorii. AB - D-Tagatose 3-epimerase (D-TE) from Pseudomonas cichorii catalyzes the epimerization of various ketohexoses at the C3 position. The epimerization of D psicose has not been reported with epimerases other than P. cichorii D-TE and D psicose 3-epimerase from Agrobacterium tumefaciens. Recombinant P. cichorii D-TE has been purified and crystallized. Crystals of P. cichorii D-TE were obtained by the sitting-drop method at room temperature. The crystal belongs to the monoclinic space group P2(1), with unit-cell parameters a = 76.80, b = 94.92, c = 91.73 A, beta = 102.82 degrees . Diffraction data were collected to 2.5 A resolution. The asymmetric unit is expected to contain four molecules. PMID- 17277457 TI - Crystallization and preliminary X-ray diffraction study of glycerol kinase from the hyperthermophilic archaeon Thermococcus kodakaraensis. AB - Glycerol kinase from the hyperthermophilic archaeon Thermococcus kodakaraensis was crystallized and preliminary crystallographic studies of the crystals were performed. Crystals were grown at 293 K by the sitting-drop vapour-diffusion method. Native X-ray diffraction data were collected to 2.4 A resolution using synchrotron radiation at station BL44XU of SPring-8. The crystal belongs to the rhombohedral space group R3, with unit-cell parameters a = b = 217.48, c = 66.48 A. Assuming the presence of two molecules in the asymmetric unit, the V(M) value was 2.7 A(3) Da(-1) and the solvent content was 54.1%. The protein was also cocrystallized with substrates and diffraction data were collected to 2.7 A resolution. PMID- 17277458 TI - Purification, partial characterization, crystallization and preliminary X-ray diffraction of a novel cardiotoxin-like basic protein from Naja naja atra (South Anhui) venom. AB - A novel cardiotoxin-like basic protein was isolated from the venom of the Chinese cobra (Naja naja atra) from the south of Anhui in China. The protein inhibits the expression of vascular endothelial growth factor and basic fibroblast growth factor in human lung cancer cell line H1299 and induces the haemolysis of rabbit erythrocytes under low-lecithin conditions. After a two-step chromatographic purification, the resultant 7 kDa protein was crystallized by the hanging-drop vapour-diffusion method at room temperature. A complete data set was collected to 2.35 A resolution using an in-house X-ray diffraction system. The crystal belongs to space group P4(1)2(1)2, with unit-cell parameters a = b = 43.2, c = 147.9 A. There are two molecules in the crystallographic asymmetric unit. PMID- 17277459 TI - The use of in situ proteolysis in the crystallization of murine CstF-77. AB - The cleavage-stimulation factor (CstF) is required for the cleavage of the 3'-end of messenger RNA precursors in eukaryotes. During structure determination of the 77 kDa subunit of the murine CstF complex (CstF-77), it was serendipitously discovered that a solution infected by a fungus was crucial for the crystallization of this protein. CstF-77 was partially proteolyzed during crystallization; this was very likely to have been catalyzed by a protease secreted by the fungus. It was found that the fungal protease can be replaced by subtilisin and this in situ proteolysis protocol produced crystals of sufficient size for structural studies. After an extensive search, it was found that 55% glucose can be used as a cryoprotectant while maintaining the diffraction quality of the crystals; most other commonly used cryoprotectants were detrimental to the diffraction quality. PMID- 17277460 TI - Crystallization and preliminary X-ray crystallographic analysis of the receptor uncoupled mutant of Galphai1. AB - In order to understand the molecular mechanisms by which G-protein-coupled receptors (GPCRs) activate G proteins, the K349P mutant of Galpha(i1) (K349P), which is unable to couple to the muscarinic acetylcholine receptor, was prepared and its crystals were grown along with those of wild-type Galpha(i1) protein (WT). The two proteins were crystallized under almost identical conditions, thus enabling a detailed structural comparison. The crystallization conditions performed well irrespective of the identity of the bound nucleotide (GDP or GTPgammaS) and the crystals diffracted to resolutions of 2.2 A (WT.GDP), 2.8 A (WT.GTPgammaS), 2.6 A (K349P.GDP) and 3.2 A (K349P.GTPgammaS). PMID- 17277461 TI - Crystallization and preliminary X-ray crystallographic studies of Pz peptidase A from Geobacillus collagenovorans MO-1. AB - Pz peptidase A is an intracellular M3 metallopeptidase found in the thermophile Geobacillus collagenovorans MO-1 that recognizes collagen-specific tripeptide units (Gly-Pro-Xaa). Pz peptidase A shares common reactions with mammalian thimet oligopeptidase (TOP) and neurolysin, but has extremely low primary sequence identity to these enzymes. In this work, Pz peptidase A was cocrystallized with a phosphine peptide inhibitor (PPI) that selectively inhibits TOP and neurolysin. The crystals belong to space group P2(1), with unit-cell parameters a = 56.38, b = 194.15, c = 59.93 A, beta = 106.22 degrees . This is the first crystallographic study of an M3 family peptidase-PPI complex. PMID- 17277463 TI - Initiation and progression of superficial bladder cancer: Can genes provide the key? PMID- 17277464 TI - Sinonasal T-Cell lymphomas: A clinicopathologic study of a possibly distinct entity. AB - BACKGROUND: Most cases of sinonasal lymphomas reported in the literature which show positive expression for Epstein-Barr virus are CD2+, CD3-, CD43+ and CD56+, and also show a germ-line T-cell receptor genotype. Five-year survival is usually around 50%. We report a group of patients with T-cell sinonasal lymphoma that showed distinct immunophenotypic and molecular profiles and a more aggressive behavior. PATIENTS AND METHODS: Nineteen cases representing approximately 75% of sinonasal lymphoma diagnosed and treated at our institution between 1988 and 1997 were studied. They comprised 12 males and 7 females, with an age range of 10 to 73 years (median 46 years). The remaining cases (about 25%) were B-cell lymphomas. The morphology of the cases was evaluated together with a limited immunophenotyping. In situ hybridization for EBV mRNA was performed in 18 cases. Polymerase chain reaction (PCR) for T-cell receptor (TCR) gene rearrangement was performed in 15 cases. Clinical follow-up information was available on 14 patients. All cases showed a pattern of large-cell lymphoma, and three exhibited an immunoblastic morphology. The tumors showed extensive soft tissue invasion, necrosis and ulceration. While perineural invasion was a prominent feature, perivascular invasion was not noticed. RESULTS: Seventeen tumors (84%) were CD3 positive. PCR analysis showed TCR gene rearrangement in 7 of 15 cases (46%). Fifteen cases (79%) were positive for EBV. The 14 patients with available clinical information had extensive local diseases, with stages ranging from IE to IIIE, where none showed positive bone marrow involvement. The 14 patients received chemotherapy with or without radiation therapy. Ten of the 14 patients (71%) died of the disease after a median of seven months, including all seven patients with positive TCR gene rearrangement. CONCLUSION: Our findings suggest that sinonasal T-cell lymphoma represents a heterogeneous group of diseases with different phenotypic, genotypic and biological characteristics. Cases that show TCR gene rearrangement may represent a more aggressive subtype of the disease. PMID- 17277465 TI - Analysis of the apolipoprotein B gene 3' hypervariable region among nationals of the Abu Dhabi Emirate and comparisons with other populations. AB - BACKGROUND: Among all the polymorphic markers available to date, a hypervariable region located in the 3' of the human apolipoprotein B gene has been extensively studied in global populations throughout the world. PATIENTS AND METHODS: Using a polymerase chain reaction-based assay, we investigated the allele and genotype frequency distributions of the alleles (corresponding to repeats of a 30 base pair core DNA sequence) of this hypervariable region in a group of 367 unrelated nationals (201 males, 166 females) from the United Arab Emirates. RESULTS: We found 18 different alleles, ranging from 21 to 55 repeats, making up 51 genotypes that occurred in Hardy-Weinberg proportions and were associated with a heterozygosity index of 80.9%. The allele frequency distribution was different from that of other populations in that it was trimodal, with peaks at 31, 37 and 47 repeats, with corresponding relative frequencies of 16.1%, 25.1% and 6.0%. A four-allele model, which allowed comparisons with other reports, revealed distribution differences with all other ethnic groups except South Asians and Serbs. CONCLUSION: This marker is very informative for the Emirati population, and will be very useful for UAE-specific DNA fingerprinting. It will also be a valuable tool for assessing the role of apolipoprotein B in cardiovascular diseases. PMID- 17277466 TI - Use of FISH analysis for diagnosis of renal cell carcinoma subtypes. AB - BACKGROUND: Cytogenetic and molecular genetic techniques have been used in demonstrating the chromosomal abnormalities which characterize specific subtypes of renal cell carcinoma (RCC). The aim of this study was to determine the efficiency of fluorescent in situ hybridization (FISH) technique in characterizing various subtypes of RCC based on the presence of specific chromosome abnormalities found in each RCC subtype. MATERIALS AND METHODS: FISH was performed on touch imprint smears from eight renal cell carcinomas histologically confirmed by established criteria. RESULTS: In four tumors with histologic features of chromophobe renal cell carcinoma (ChRCC), interphase FISH was performed using centromeric probes for chromosomes 1, 2, 6, 10, 12, 17 and 21. All four ChRCC tumors showed one FISH signal corresponding to one copy number for each of these chromosomes. Two papillary RCCs included in this study showed trisomy 7 and 17, and loss of chromosome Y, using the corresponding chromosome centromeric probes. Similarly, we tested two clear cell RCCs for chromosome 3 short arm deletion with DNA probe 3p21.3. Both tumors showed loss of 3p21.3 signal. CONCLUSION: We conclude that interphase FISH performed on touch imprint smears is a relatively simple, rapid and reliable method for detecting chromosome abnormalities which are specific for various subtypes of RCC. PMID- 17277467 TI - Congenital diaphragmatic hernia: A local experience. AB - BACKGROUND: The objective of this study was to review infants with congenital diaphragmatic hernia (CDH) from the clinical and surgical aspects, and to analyze the risk factors affecting the outcome. PATIENTS AND METHODS: The records of 33 infants with CDH who were admitted to the Neonatal Intensive Care Unit (NICU) from January 1989 to July 1996 were retrospectively reviewed. The mean gestational age was 38.87A+/-2.6 weeks and the mean birth weight was 2896A+/-700 g. The male to female ratio was 2:1. Twenty-six infants had left-sided and seven had right-sided CDH. All infants required mechanical ventilation within six hours of being born. RESULTS: Nineteen infants survived until hospital discharge and 14 infants died, giving an overall mortality rate of 43%. We noted that pH of less than 7.3, PaCO2 of more than 45 mm Hg, or peak inspiratory pressure of more than 25 cm, were associated with high mortality. A higher risk of mortality was also seen in infants with persistent pulmonary hypertension of the newborn (PPHN). Survival rate was observed to be slightly higher in infants who had surgical repair beyond 48 hours of age. Survivors and nonsurvivors were comparable in terms of a 5-minute Apgar score, sex, mode of delivery, PaCO2 at presentation, the site of diaphragmatic defect, air leak syndrome, associated congenital heart disease, and the presence of stomach or viscera in the thorax. CONCLUSION: High ventilatory support and moderate-to-severe respiratory acidosis at presentation and PPHN during hospital course were found to be associated with high mortality. PMID- 17277468 TI - A study of membranoproliferative glomerulonephritis in Iran. AB - BACKGROUND: The aim of this study was to review the morphologic patterns of membranoproliferative glomerulonephritis (MPGN) in 100 Iranian patients using light microscopy (LM) and electron microscopy (EM), and to compare the treatment and outcome in 13 patients with two biopsies. PATIENTS AND METHODS: A retrospective study of 713 kidney biopsies of Iranian patients received between 1981 to 1994 was carried out. Of the 713 kidney biopsies, MPGN (n=106) and membranous glomerulopathy (n=112) made up the highest numbers of cases. RESULTS: Among 100 MPGN patients, 55 (55%) were MPGN type I, 10 were type II (10%), and 35 type III (35%). Eighty-three (83%) had nephrotic proteinuria, 39 (39%) had hematuria, and 52 (52%) were hypertensive. Complement levels were estimated in 58, with low C3 in 10. The glomerular involvement was irregular, with focal hypercellularity in 47 patients (47%), widely patent capillaries in 50 (50%), arteriosclerosis in 48 (48%), and with hyaline change in 25 (25%). Follow-up data (22-130 months) was available in 61 (61%) patients: 6 (10%) died after 14-56 months, 27 (44%) were on maintenance hemodialysis for 15-110 months, and three received transplants. Thirteen patients had detailed follow-up and a second biopsy after 24-120 months. All 13 presented with edema and nephrotic range proteinuria, with hematuria and hypertension in five and azotemia in four. Seven of the 13 patients received initial steroids, followed by antiplatelet or antihypertensive drugs. Four (type III) patients received antiplatelet and antihypertension drugs, and two (type III) received only antihypertensive drugs. In the first biopsy, glomerular changes by light microscopy were non-uniform in 7 of 10 (70%) type III MPGN cases. Vascular changes were absent or mild in 11, and moderate in two. In the second biopsies, 10 showed decrease in cellularity, with many open capillaries, persistence of deposits by EM in all, and progression of vascular sclerosis in eight, and tubulointerstitial changes in 10. Among the 13, six were clinically stable, another six received dialysis followed by transplant in three, and one had relapses with episodes of cryoglobulinemia. Three patients died. CONCLUSION: There is a high incidence of MPGN in Iranian patients, with a substantial number of type III MPGN cases. Second biopsies showed decreased cellularity, but increase in chronic tubulointerstitial and vascular cases. Steroids did not appear to benefit the outcome in types I and III MPGN patients compared to patients who received antihypertensive and antiplatelet treatment without steroids. PMID- 17277469 TI - Emotional distress in women presenting for breast imaging. AB - BACKGROUND: The aim of this study was to assess anxiety and depression in a sample of women presenting for imaging of the breast following a clinical referral. Emotional distress in the women was also assessed in relation to demographic factors, reason for referral, presence of breast symptoms, type of imaging procedure performed, and self-reported pain and discomfort during imaging. PATIENTS AND METHODS: The study comprised 167 patients. The Hopkins Symptom Checklist-25 (HSCL-25) and a discomfort rating scale were used to assess emotional distress and discomfort or pain experienced during the imaging. RESULTS: While less than 10% of all subjects scored above psychiatric cut-off points for anxiety and depression, 25% and 20% reported significant distress associated with anxiety and depression symptoms, respectively. Education alone was associated with higher anxiety scores, while the presence of breast symptoms significantly increased depression scores and reports of specific nonsomatic symptoms of depression. Higher anxiety and depression scores were also associated with pain experienced during the imaging procedure. CONCLUSION: Emotional distress may negatively impact womenas experience of breast imaging. Screening for emotional distress is important within the context of breast imaging. PMID- 17277470 TI - What's your diagnosis? Neuronal ceroid lipofuscinosis. PMID- 17277471 TI - Effect of diabetes mellitus on quality of life: A review. PMID- 17277472 TI - Fibrodysplasia ossificans progressiva. PMID- 17277473 TI - Congenital (granular cell) epulis of the newborn: A case report with immunohistochemical study on the histogenesis. PMID- 17277474 TI - Paradoxical enlargement of lymph nodes during therapy of central nervous system tuberculosis. PMID- 17277476 TI - Congenital absence of oval window. PMID- 17277475 TI - Rhodotorula rubra fungemia in an immunocompromised patient. PMID- 17277478 TI - Congenital diaphragmatic hernia: The impact of preoperative stabilization on outcome. PMID- 17277477 TI - Listeria mMonocytogenes bacteremia and meningitis in a Saudi newborn. PMID- 17277479 TI - Rupture of the pubic symphysis: Diagnosis, treatment and clinical outcome. PMID- 17277480 TI - Storing insulin in a clay pot in the desert causes no loss of activity: A preliminary report. PMID- 17277481 TI - The value of postictal electroencephalogram in temporal lobe seizures. PMID- 17277482 TI - Unresectable hepatoblastoma: The role of preoperative chemotherapy. PMID- 17277483 TI - Hypertensive disorders of pregnancy: Prevalence, classification and adverse outcomes in northwestern Saudi Arabia. PMID- 17277484 TI - Necrotizing enterocolitis in Saudi Arabia: Experience in a referral neonatal intensive care unit. PMID- 17277485 TI - Chest pain asthma: A neglected variant? PMID- 17277486 TI - Coarctation of the aorta: A call for early detection. PMID- 17277487 TI - Reply: Coarctation of the aorta: A call for early detection. PMID- 17277492 TI - Deltamethrin-impregnated bed nets and curtains in an anthroponotic cutaneous leishmaniasis control program in northeastern Iran. AB - BACKGROUND: Anthroponotic cutaneous leishmaniasis (ACL) has long been a significant public health problem in northeastern Iran. The objective of this study was to determine the efficacy of deltamethrin-impregnated vs. nonimpregnated bed nets (NIBs) and curtains (NICs) in ACL control. PATIENTS: Deltamethrin-impregnated bed nets (IBs) and curtains (ICs) with 25 mg ai/m2 were distributed among 160 households in one district and NIBs and NICs were distributed among the same number of households in another district. A third district with a similar numbers of households served as a control. Health education mes- sages were disseminated to ensure the populationas complicance with the proper use of bed nets and curtains. Sticky paper traps were used to assess the effect of insecticide-impregnated bed nets and curtains on the density of Phlebotomus sergenti. Deltamethrin susceptibility and also bioassay tests were carried out on the species by WHO standard method. Case findings were done by house-to-house visits once a season and all the inhabitants of the selected households in each district were examined. RESULTS: IBs and ICs provided good protection against sandfly bites and reduced the transmission of ACL in the intervention district, while NIBs and NICs provided no protection. There was no significant difference in monthly density of P. sergenti indoors and outdoors among the districts (P>0.05). This species was susceptible to delta- methrin in the field population in the area. Bioassays confirmed that the nets treated with deltamethrin remained effective for more than 3 months. CONCLUSION: Personal protection is an effective and sustainable means of preventing and controlling ACL and can reduce dependence on insecticides. We encourage the use of IBs and ICs to control ACL in other high-risk areas of Iran and Afghanistan during the active season of sandflies. PMID- 17277494 TI - Pulmonary amyloidosis in a patient with lymphocytic interstitial pneumonia. PMID- 17277495 TI - Portal-mesenteric vein thrombosis as an unusual presentation of Meckel's diverticulum complication. PMID- 17277497 TI - Gigantic cerebral hydatid cysts in childhood. PMID- 17277496 TI - Human papilloma virus-16/18 cervical infection among women attending a family medical clinic in Riyadh. AB - BACKGROUND: Prevalence information is lacking on human papillomavirus types 16 and 18 (HPV-16/18) infection in cervical tissues of women residing in Riyadh, Saudi Arabia. In addition, there are no observations on progression to cervical intraepithelial neoplasia (CIN). SUBJECTS AND METHODS: Pap smear and HPV-16/18 DNA detection by PCR followed by Southern blotting was performed on 120 subjects (Saudi and other Arab nationals) during routine gynecological examination. Some HPV-positive subjects were followed for 4 years, by Pap smear every 6 months and by HPV DNA detection at the end of 4 years. RESULTS: Overall HPV-16/18 prevalence was 31.6%. HPV-16 prevalence alone was 13.3%, HPV-16 as a mixed infection with HPV-18 was 15%, and all HPV-16 was 28.3%. HPV-18 alone was 3.3%, HPV-18 as a mixed infection with HPV-16 was 15%, and all HPV-18 was 18.3%. Ten subjects had cervical abnormalities with the Pap smear test, six of whom were HPV-16/18 positive, 1 with HPV-16, 1 with HPV-18, and 4 with a mixed infection of HPV 16/18. Of all 23 HPV-16/18-positive subjects, either as individual or mixed infection, followed for 4 years, 7 showed abnormal cytology, 6 at initial examination and 1 during follow-up. Of these 7, 6 reverted to normal without treatment and 1 was treated and became normal after 3 years. None of the subjects progressed to CIN-III. CONCLUSION: A high prevalence of HPV-16/18 was found, but with a low rate of progression to CIN. A significant association with abnormal cytology was found only in patients with HPV-16/18 mixed infection. PMID- 17277498 TI - Bronchiolitis obliterans organizing pneumonia: experience at three hospitals in Riyadh. AB - BACKGROUND: Because reports of bronchiolitis obliterans organizing pneumonia (BOOP) are lacking from the Middle East, we conducted a retrospective review of of all histopathologically proven cases of BOOP over a 10-year period at three tertiary care hospitals in Riyadh and describe the clinical features and outcome. METHODS: Charts at the three hospitals were searched using a specific code for BOOP or cryptogenic organizing pneumonia (COP). Lung specimens had to show histological proof of BOOP with a compatible clinical picture. Chest radiographs and high-resolution CT scans were reviewed. RESULTS: Twenty cases of biopsy proven BOOP had well-documented clinical and radiographic data. There were 11 males and 9 females (mean age, 58 years; range, 42-78). The clinical presentation of BOOP was acute or subacute pneumonia-like illness with cough (85%), fever (70%) dyspnea, (85%) and crackles (80%). The most frequent radiological pattern was a bilateral alveolar infiltrate. The most common abnormality on pulmonary function testing (n=14) was a restrictive pattern (11 patients). Most patients (70%) had no underlying cause (idiopathic BOOP). Other associations included thyroid cancer, rheumatoid arthritis, syphilis and Wegner's granulomatosis. Ten patients (50%) had a complete response to steroids, 6 (30%) had a partial response and 3 (15.8%) with secondary BOOP had rapid progressive respiratory failure and died. CONCLUSION: The clinical presentation of BOOP in our patients is similar to other reported series. A favorable outcome occurs in the majority of cases. However, BOOP may occasionally be associated with a poor prognosis, particularly when associated with an underlying disease. PMID- 17277499 TI - Metabolic syndrome in normal-weight Iranian adults. AB - BACKGROUND: This study provides the first reported estimates of the prevalence of the metabolic syndrome in a normal-weight Iranian population. SUBJECTS AND METHODS: In this population-based cross-sectional study, the study population consisted of a representative sample of 1737 males and 1707 females aged > or = 20 years with normal body mass index (BMI) (18.5-24.9 kg/m2 for both genders). The metabolic syndrome was defined according to the Adult Treatment Panel III guidelines. We present means and proportions, and multivariate odds ratios that quantify the association between metabolic syndrome and normal BMI quartiles, controlling for age, physical activity, smoking and education. RESULTS: The overall prevalence of the metabolic syndrome in normal-weight men and women were 9.9% and 11.0% (P=0.2) respectively. Men had a lower BMI than women, while their waist circumference (WC) was higher. The prevalence of high WC and low high density lipoprotein cholesterol (HDL-C) was higher in women, while high blood pressure, high triglyceride levels and having at least one metabolic risk factor were more prevalent in men. Individuals in the highest category of normal BMI had significantly higher odds for being at risk for metabolic syndrome compared to those in the first category (OR: 5.21 for men and 2.15 for women). There was an increasing trend in odds for having all the metabolic syndrome components except for high fasting blood sugar (FBS) and high WC in men. Women showed a similar increasing trend except for high FBS across normal BMI quartiles. CONCLUSION: The prevalence of the metabolic syndrome in normal-weight Iranian adults is relatively high. Therefore, interventions for prevention of cardiovascular disease could be considered in this population. PMID- 17277500 TI - Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in Bahrain: a nationwide primary care diabetes clinic-based study. AB - BACKGROUND: Although epidemiological studies have persistently shown a high prevalence of diabetes in Arabs, the control of diabetes is still poor and complications of diabetes are common. We examined the prevalence of diabetic peripheral neuropathy (DN), neuropathic foot ulceration (FU) and peripheral vascular disease (PVD), and potential risk factors for these complications among patients attending primary care diabetes clinics in Bahrain. PATIENTS AND METHODS: We studied 1477 diabetic patients (Type 2 diabetes 93%); to, including 635 men and 842 women, with ages ranging from 18-75 years in a cross-sectional study. The main predictor variables were demographic and clinical data, including assessment of foot and blood parameters. RESULTS: Mean age of the patients and duration of diabetes were 57.3 +/- 6.32 and 9.5 +/- 8.4 years, respectively. DN was present in 36.6% of the population, FU in 5.9%, and PVD in 11.8%. Diabetic patients with neuropathy were older than patients without neuropathy (P=0.001) and had had diabetes longer (P=0.002). Diabetic patients with foot ulcers had more severe neuropathy and higher vibration perception thresholds values than patients without foot ulcers (P<0.05). Older age, poor glycemic control, longer duration of diabetes, elevated cholesterol levels, current smoking, obesity defined by body mass index, large waist circumference, elevated triglycerides levels and hypertension but not gender, were significant risk factors for DN in both the univariate and the multivariate analyses (P< 0.05). DN and PVD also remained significant risk factors for foot ulceration in the multiple logistic regression analysis. CONCLUSION: Rates of DN and PVD are high among diabetic patients in Bahrain. Implementation of strategies for prevention, early detection, and appropriate treatment at the primary health care level are urgently needed. PMID- 17277501 TI - A case of urinary bladder benign polyp treated successfully by resection in a child. PMID- 17277502 TI - The role of endoscopy in childhood chronic abdominal pain. PMID- 17277503 TI - Brucellosis in Saudi Arabia: Past, present and future. PMID- 17277504 TI - Sleep disorders in Saudi health care workers. AB - BACKGROUND: The objective of the study was to screen for sleep habits and various sleep disorders, using a standard questionnaire. PATIENTS AND METHODS: The questionnaire was designed to assess sleep habits, the degree of daytime sleepiness using the Epworth Sleepiness Scale (ESS), and specific sleep problems. A random sample of Saudi employees working as medical or paramedical personnel was selected. RESULTS: There were 163 respondents (65%) comprising 33 females and 130 males. The mean ESS score was 9.4. Sixty-four respondents (39.3%) had an ESS score of more than 10, i.e., excessive daytime sleepiness (EDS). When subjects with poor sleep habits and/or sleep problems were excluded, there were 65 anormala sleepers, with a mean ESS score of 8.9+/-3.6. This did not differ from the rest of the sample population, who had a score of 9.8+/-3.7 (P=0.15). Subjects with inadequate sleep or insomnia consisted of 17 females (51.5%) and 45 males (34.6%). There were seven subjects, all males (5.4%), with habitual snoring. Ten males (7.7%) and two females (6.1%) reported having breathing pauses while asleep. Symptoms of restless leg syndrome, sleep paralysis, and cataplexy were reported by 21 (12.9%), 26 (16.0%) and two (1.2%) subjects, respectively. CONCLUSION: The prevalence of EDS in the Saudi population is higher compared to that reported from other populations when a Western ESS normal range is used. Nevertheless, the range of normal score of ESS is probably broader for Saudis compared to other populations. In general, sleep disorders are common but unrecognized in our community. PMID- 17277505 TI - Hepatitis C virus genotypes in a cohort of Middle Eastern patients. AB - BACKGROUND: The epidemiology of hepatitis C virus infection has been well characterized in Western Europe, North America and Japan. Less is known about it in other regions of the world. In order to fully understand the relationship between host and virus, it is important to study the effect of virus infection in all regions of the world. In this report, we have analyzed patients from the United Arab Emirates, Egypt and Jordan. DESIGN AND METHODS: Serum from 81 Middle Eastern HCV ELISA-2-positive patients was analyzed for the presence of HCV RNA by PCR. RNA-positive patients were genotyped by selective hybridization of amplicons to HCV genotype-specific oligonucleotides (InnoLipa2, Innogenetics, Belgium). Where possible, data was also obtained on racial origin, liver histology, serum ALT, prothrombin time, albumin, and risk factors for infection. RESULTS: Sixty five of 81 patients were HCV RNA-positive. A higher proportion of Middle Eastern patients were genotype 4 compared to equivalent studies from Western Europe, USA and Japan. However, the most common genotype was 1a. No significant difference in genotype was found between patients with chronic hepatitis and patients with cirrhosis. CONCLUSIONS: Eight of 65 (12%) patients were genotype 4, but the most common genotype was 1a, a aWesterna genotype (24/65, 37%). The mean age of cirrhotics was low compared to Western studies. This may be due to infection in early childhood or race-related host factors. Twelve of 65 patients (18%) were not classifiable for genotype using InnoLipa2. This may be due to multiple infecting genotypes in these patients, or unusual, non 13 HCV genotypes which cannot be classified by InnoLipa2. PMID- 17277506 TI - ANCA-associated glomerulonephritis: Relationship of main ANCA subtypes to renal outcome, age and sex of the patients. AB - BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) have been proven to be useful diagnostic tools in patients with systemic vasculitis and glomerulonephritis. These antibodies exist in two types, a cytoplasmic pattern (cANCA) and a perinuclear pattern (pANCA). The effect of the main ANCA subtypes on renal outcome and its relationship to demographic findings and clinical features of patients with ANCA-associated glomerulonephritis has not been adequately studied. PATIENTS AND METHOD: In this prospective study, we compared the clinical features at presentation and the renal outcome after 1 year of follow-up between two groups of patients with cANCA (n=22) and pANCA (n=29) consecutively encountered over a one-year period. RESULT: At presentation, rapidly progressive glomerulonephritis (RPGN), and after 1 year of follow-up, endstage renal disease (ESRD) were seen more commonly in patients with pANCA than cases with cANCA (P=0.001 and P=0.004, respectively). Seropositivity for cANCA was more common in male and pANCA in female patients (P=0.005). Occurrence of the pulmonary-renal syndrome or extra-renal manifestations, such as sinusitis and skin rash, did not differ significantly among the two groups of patients with cANCA and pANCA. CONCLUSION: Patients with pANCA present more frequently with RPGN, leading to a poorer renal survival compared to cases with cANCA. RPGN and pANCA are more common in females. PMID- 17277507 TI - Immunogenicity of FDA DTP versus WHO DTP. AB - BACKGROUND: The aim of this report was to study the immunogenicity of three doses of DTP in six-week-old Saudi infants when given either as World Health Organization (WHO) DTP or Federal Drug Administration (FDA) DTP formula. METHODS: As part of the Haemophilus influenzae type b immunization research protocol, six week-old infants were randomized into three groups to receive three doses of HbOC and WHO DTP formula, HbOC and FDA DTP formula, or in a control group to receive the usual vaccines without HbOC, at six weeks, three months and five months. Antibody levels for PRP, tetanus, diphtheria and pertussis were measured after the third dose. The results of diphtheria, pertussis and tetanus are presented in this paper. RESULTS: After three doses, no difference was found between anti-PRP when given with either FDA DTP or WHO DTP formula. Also anti-tetanus and anti diphtheria antibodies were significantly higher in the group vaccinated with HbOC and FDA DTP formula, compared to children vaccinated with WHO DTP formula. No negative interactions with other vaccines were observed after the third dose. Conclusion. Although diphtheria and tetanus antigens in the FDA formula are half the concentration in the WHO formula, they are more antigenic. There is a need for methods of potency assay to be re-evaluated. PMID- 17277509 TI - Factors influencing job satisfaction among primary health care (PHC) physicians in Riyadh, Saudi Arabia. PMID- 17277508 TI - How the discrepancy between symptoms and peak expiratory flow rate influences evaluation of asthma severity. AB - BACKGROUND: Recent asthma guidelines recommend the assessment of severity levels based on the most severe symptoms and peak expiratory flow rate (PEFR). Discrepancies are frequently encountered in the use of these variables in determining the severity levels of asthmatics. The objective of this study was to determine the difference in asthma severity levels as assessed by either symptoms alone or by PEFR alone, as compared with the assessment by the asthma guidelines. PATIENTS AND METHODS: Severity levels that were determined by recent asthma guidelines for 60 asthmatic patients were reassessed, based on symptoms alone and PEFR alone. They were compared for any significant differences to the asthma guidelines. RESULTS: Asthmatics were aged between 15 and 70 (mean 34) years, and 63.8% were females. Severity levels by symptoms alone were different from the guidelines in 27 cases (45%). Of these, 89% showed a tendency toward higher severity levels. Severity levels by PEFR alone were different in only three cases (5%). In both comparisons, differences of severity levels were significant (P<0.0001), but assessment by symptoms alone showed more deviation (x(2) =162.1) than PEFR alone (x(2) =73.1). CONCLUSION: The study documented significant discrepancies in asthma severity assessed by symptoms alone and PEFR alone, when compared to the recent asthma guidelines. Severity assessed by symptoms alone showed lower levels, and the use of PEFR tended to categorize some asthmatics into a more severe level. PMID- 17277510 TI - Abdominal aortic aneurysm in infant. PMID- 17277511 TI - Bacterial endocarditis presenting with decreased vision. PMID- 17277512 TI - Parathyroid carcinoma: A report of two cases. PMID- 17277513 TI - Anticipation in a family with autosomal dominant spinocerebellar ataxia. PMID- 17277514 TI - Ovarian cancer recurrence at the laparoscopic port for cholecystectomy. PMID- 17277515 TI - Duodenal varices causing massive lower gastrointestinal hemorrhage. PMID- 17277516 TI - Scorpion envenomation in children: Should all stings be given antivenom? PMID- 17277518 TI - Epidemiology of hydatid disease in Riyadh: A hospital-based study. PMID- 17277517 TI - The frequency of IgE antibodies specific to inhalant and food allergens in adult asthmatic patients in Riyadh, Saudi Arabia. PMID- 17277519 TI - Pattern of skin diseases at King Khalid National Guard Hospital: A 12-month prospective study. PMID- 17277520 TI - Primary hyperparathyroidism and vitamin D deficiency: A combination still encountered in Asian countries. PMID- 17277521 TI - A more positive diagnosis of irritable bowel syndrome in Saudi patients. PMID- 17277523 TI - Trends in rates of delivery of extremely low birth weight babies in Afif, Saudi Arabia. PMID- 17277522 TI - Black fire ant (Solenopsis richteri) sting producing anaphylaxis: A report of 10 cases from Najran. PMID- 17277525 TI - Sildenafil (Viagra) may cause nasal stuffiness. PMID- 17277524 TI - Cardiac angiosarcoma presenting as right heart failure secondary to pulmonary vascular carcinomatosis. PMID- 17277526 TI - Evidence-based medicine for the new millennium: Critical appraisal and pragmatic approach. PMID- 17277527 TI - Evidence-bases medicine: What is the evidence? PMID- 17277528 TI - Liposarcoma: A clinicopathological study of 73 cases diagnosed at King Faisal Specialist Hospital and Research Centre. AB - BACKGROUND: Liposarcoma is one of the most common adult soft tissue sarcomas, being second only to malignant fibrous histiocytoma. It ranges from the well differentiated lipoma-like and myxoid tumors, to extremely cellular or pleomorphic malignant neoplasms. The clinical behavior is variable and reflects the variable microscopic picture. PATIENTS AND METHODS: Clinicopathological studies of liposarcoma in Saudi Arabia are lacking. In this study, we reviewed all liposarcoma cases reported at KFSH&RC from 1981 to 1996. Seventy-three cases of liposarcoma were studied morphologically. The cases were classified using the WHO International Classification of Diseases (ICD). Data regarding follow-up, mode of therapy, recurrence and survival status were available for 37 cases (50.68%). Survival analysis was performed. The patientsa ages ranged from 15-94 years, with peak incidence between the ages 40 and 60 years. There was a male predominance of 1.3:1. RESULTS: The most common location was the thigh (36 cases), accounting for 49.3% of cases, followed by the retroperitoneum (16 cases), accounting for 21.9%. The most common histologic type was myxoid liposarcoma (41 cases; 56.2%), followed by well-differentiated liposarcoma (16 cases; 21.9%), including dedifferentiated liposarcoma (5 cases; 6.8%), pleomorphic liposarcoma (13 cases; 17.8%) and round-cell liposarcoma (3 cases; 4.1%). Twenty-two patients (59.45%) were treated by surgery only, and 13 patients (35.13%) were treated by a combination of surgery and postoperative radiotherapy. One patient was treated by surgery, radiotherapy and chemotherapy, and died one month after diagnosis. Another patient was treated by radiotherapy alone and is still alive after a four-year follow-up period. The correlation between survival and recurrence with tumor type, location in regard to surgical accessibility, and mode of therapy, was not statistically significant. CONCLUSION: Site, histologic type and completeness of surgical excision were the most important factors in predicting prognosis and planning therapy for patients with liposarcoma. The overall prognosis depends on many variable factors. Complete surgical excision reduces the recurrence rate. The role of chemotherapy and radiotherapy is not well established. PMID- 17277529 TI - Lipids and related parameters in Saudi type II diabetes mellitus patients. AB - BACKGROUND: Non-insulin dependent diabetes mellitus (type II DM) is frequently associated with abnormal levels of lipids, particularly in patients with poor diabetic control. This study was designed to investigate the influence of type II DM on levels of plasma lipids and other related parameters in Saudi patients. Saudi Arabia has a high prevalence of diabetes mellitus in the adult population. Since the Saudi population presents a unique group with different dietary habits, lifestyle and genetic make-up, we investigated the lipids, lipoprotein and apolipoprotein pattern in Saudi type II DM patients. MATERIALS AND METHODS: This study was conducted on 2835 diabetic patients (1361 males, 1474 females) and 200 age-matched healthy adults from the same areas with no history of diabetes mellitus. Data collected included height, weight, body mass index (BMI), blood pressure and other relevant parameters. Lipids, lipoproteins and apolipoproteins were estimated, and correlation studies were carried out between these parameters. Lipids, lipoproteins and apolipoproteins were also correlated with the fasting blood glucose. RESULTS: Our results showed significant elevation in cholesterol and triglyceride, apo A and apo B levels in the diabetic males and females compared to the controls. Approximately 37% of the total DM patients fell in the borderline risk group, while 28.4% fell in the high-risk group for development of cardiovascular disease. Lipoproteins did not differ significantly. Cholesterol, triglyceride, VLDL, LDL and Hb A1c correlated positively with glucose (P<0.05), while triglyceride, VLDL, HDL, LDL, apo A and apo B showed significant correlation with cholesterol, where all parameters increased with cholesterol except HDL, which decreased as cholesterol increased. CONCLUSION: The findings point toward high prevalence of dyslipidemia in type II DM Saudi patients. PMID- 17277530 TI - Familial clustering of type II diabetes mellitus (DM) diagnosed under the age of 40 years in Yemen: Is it early-onset type II DM or maturity-onset diabetes of the young? AB - BACKGROUND: Clinical presentation of type II diabetes mellitus (DM) has frequently been observed at an early age in developing countries, probably as a result of genetic, epidemiological and demographic factors. This study aimed to investigate the pattern of familial clustering of type II DM in patients who developed clinical diabetes before the age of 40 years. PATIENTS AND METHOD: The study involved family pedigrees, clinical assessments and laboratory investigations of 191 patients with type II DM, and 260 age-matched randomly selected non-diabetic controls. RESULTS: The prevalence of type II DM was found to be statistically higher among parents (P<0.0001), fullsiblings (P<0.0001), half-siblings (P<0.001), uncles (P<0.01) and aunts (P<0.001) of the index patients, as compared to the corresponding relatives of nondiabetic controls. The odds ratio of the family history index (FHI), in association with type II DM in probands who had no family history of diabetes (FHI=0.0), was significantly negative (OR=0.34; 95% CI 0.23, 0.52; P<0.0001). At an FHI level of 0.5-1.0, there was a slight nonsignificant increase in odds ratio for diabetes (OR=1.53; 95% CI 0.95, 2.45; P=0.08). A higher level of FHI (A(3)1.5) was associated with a significant increase in odds ratio for diabetes (OR=3.75; 95% CI 2.13, 6.64; P<0.0001). The age-corrected relative risk of type II DM for the offspring of diabetic parents was found to be progressively increasing from a nonconsanguineous diabetic father (22%) or mother (26.5%), to nonconsanguineous conjugal diabetic parents (27%) and to the offspring of consanguineous single or conjugal diabetic parents (37.5%). On the contrary, the age-corrected relative risk for the offspring of nonconsanguineous and consanguineous nondiabetic parents was characteristically lower (14% for each). Maturityonset diabetes of the young (MODY) was suspected in 10 probands (5%), and early-onset type II DM in the offspring of conjugal diabetic parents in 16 probands (9%). The remaining 165 probands (86%) were unclassified due to lack of specific classification criteria. CONCLUSION: The considerable familial clustering of type II DM diagnosed under the age of 40 years in this study population reflects the presence of a strong genetic component in its etiology. In addition, the development of early-onset type II DM was more likely associated with a consanguineous and/or conjugal diabetic parents and probably MODY subtype among a substantial number of patients. Epidemiological and demographic factors might have been implicated, especially in those with negative parental diabetic history. PMID- 17277531 TI - Audit of prescribing patterns in Saudi primary health care: What lessons can be learned? AB - BACKGROUND: The prescription of drugs is one of the most important factors in the rising costs of health services. The lack of proven benefit, and the definite cost and side effects of many prescriptions, have been found in many studies. The aim of the present study is to assess the prescribing pattern of primary health care (PHC) physicians in Riyadh city, the capital of Saudi Arabia. PATIENTS AND METHODS: Prescriptions issued from eight PHC centers over two weeks (six months apart) were analyzed. The health centers were randomly selected to represent the geographical parts of Riyadh city. RESULTS: A total of 17,067 prescriptions were analyzed. The most frequently prescribed drugs were antihistamines (25%), paracetamol (20.3%) and antibiotics (14.7%). Upper respiratory tract infection (URTI) was the diagnostic label used on more than half of the prescriptions. On the other hand, drugs for chronic illnesses such as diabetes mellitus (DM) and hypertension were written in a minority of the prescriptions. Antibiotics were prescribed for 26% and antihistamines for 28% of patients with URTI. Although it is well known that a large proportion of patients seen in PHC have a significant psychological or psychiatric disorder, no diagnoses of mental disorders were made. CONCLUSION: There is a pressing need for education of both patients and doctors regarding the benefit of treatment and control of chronic illnesses, and the limited contribution that the doctor or an antibiotic can make to many self limiting conditions like URTI. Doctors should be educated on more appropriate and cost-effective prescribing. The detection and management of psychological disorders need special emphasis. PMID- 17277532 TI - A hospital-based survey of primary hyperparathyroidism in the Asir Region: Low prevalence or underdiagnosis? AB - BACKGROUND: The number of patients with primary hyperparathyroidism (PHP) seen at the Asir Central Hospital (ACH) is remarkably low. This observation has raised the question of whether there is a low prevalence of PHP in the Asir region, whether it is underdiagnosed, or perhaps a combination of both factors. PATIENTS AND METHODS: A survey of 15 hospitals in the Asir region was conducted for cases of PHP. All case notes of the patients with PHP seen at ACH were reviewed. Also, a sample of patients seen at ACH was chosen randomly. The charts of those found to have hypercalcemia were reviewed for the inclusion of PHP in the diagnostic work-up. RESULTS: Only 13 patients with PHP were discovered. The eight patients with PHP seen at ACH had advanced bone manifestations and seven of them had renal manifestations. Hypercalcemia was found in 39 out of 655 patients seen at ACH. None of these had been investigated for PHP. CONCLUSION: The number of patients with PHP seen in hospitals in the Asir region is very low. Underdiagnosis seems to be an important factor. Therefore, it is felt that there is a need for greater awareness of the disease in the region. Furthermore, there is a need for a national survey to measure the prevalence of PHP in Saudi Arabia. PMID- 17277533 TI - Splenectomy for hematological diseases: The Qatif Central Hospital experience. AB - BACKGROUND: In the Eastern Province of Saudi Arabia, an area known for various hemoglobinopathies, splenectomy is performed rather frequently. This study is an analysis of our experience with splenectomy performed for various hematological disorders between 1988 and 1997, outlining the indications, complications and outcome. PATIENTS AND METHODS: This is a retrospective analysis of all patients who had splenectomy at our hospital during this period. One hundred and forty three patients were treated for various hematological disorders at our hospital. These disorders included sickle cell disease (SCD) (100 patients), sickle ss thalassemia (S-ss-thal) (13 patients), ss-thalassemia major (15 patients), Hb H disease (3 patients), idiopathic thrombocytopenic purpura (ITP) (5 patients), Gaucheras disease (2 patients), hereditary spherocytosis (1 patient), autoimmune hemolytic anemia (1 patient), thalassemia intermediate (2 patients) and chronic myeloid leukemia (1 patient). RESULTS: The indications for splenectomy in those with SCD and S-ss-thal were: hypersplenism (26 patients), major splenic sequestration crisis (23 patients), minor recurrent splenic sequestration crisis (50 patients), splenic abscess (12 patients), and massive splenic infarction (2 patients). Splenectomy in these patients was beneficial in reducing their transfusion requirements and its attendant risks, eliminating the discomfort from mechanical pressure of the enlarged spleen, avoiding the risks of acute splenic sequestration crisis, and managing splenic abscess. For those with thalassemia, total splenectomy was beneficial in reducing their transfusion requirements, while partial splenectomy was beneficial only as a temporary measure, as regrowth of splenic remnant in these patients subsequently led to increase in their transfusion requirements. Those with ITP, hereditary spherocytosis, and autoimmune hemolytic anemia showed excellent response following splenectomy. There was no mortality, and the postoperative morbidity was 5.6%. CONCLUSION: With careful perioperative management, splenectomy is both safe and beneficial in a selected group of patients with hematological diseases. PMID- 17277534 TI - Human sensitization to Prosopis juliflora antigen in Saudi Arabia. AB - BACKGROUND: Allergenicity to Prosopis juliflora pollen antigen has been reported from only a few countries, including the US, South Africa, India and Kuwait. In some parts of Saudi Arabia, species of Prosopis have been introduced by the millions as roadside ornamentation. There appear to be four flowering seasons during which pollen grains float in all directions. However, the role of Prosopis pollen as the sensitizing and/or triggering agent of allergic asthma and/or rhinitis in the Kingdom has never been evaluated. PATIENTS AND METHODS: A total of 473 allergic patients suffering from bronchial asthma in four different geographical regions (Abha, Qassim, Hofuf and Gizan), and attending allergy clinics and chest disease centers of university and Ministry of Health hospitals in the region were tested for immediate hypersensitivity reaction to Prosopis juliflora allergens. Airborne pollen grains at one center were also studied for one full year, using volumetric sampling techniques. RESULTS: A total of 76.1% patients in Qassim, 37.5% in Gizan, 29% in Abha and 11% in Hofuf reacted positively to Prosopis antigen. Multiple sensitivities to other pollen antigens were detected in all patients. The level of airborne Prosopis pollen detected in Gizan exceeded 90 grains m -3 of air. CONCLUSION: In view of the documented evidence of Prosopis-involved allergenicity, the role of Prosopis pollen as a sensitizing factor in Saudi Arabia has been confirmed. However, the cause of elicitation of symptoms in many multiple sensitive patients, together with the question of cross-reactivities, needs thorough and detailed investigation. In vitro confirmation of all positive results is also required to incriminate Prosopis as one of the major allergens in parts of Saudi Arabia. PMID- 17277536 TI - Colorectal operative experience in general surgical training at King Faisal Specialist Hospital and Research Centre. PMID- 17277537 TI - Infantile hypophosphatasia. PMID- 17277535 TI - Early detection of typhoid by polymerase chain reaction. AB - BACKGROUND: Typhoid is a common problem in developing countries. Cultivation of bacteria and serology (especially Widal test) give unacceptable levels of false negative and false-positive results, respectively. PATIENTS AND METHODS: In this study, a recently introduced polymerase chain reaction-based technique (which has 100% specificity for Salmonella typhi) was compared with blood culture and Widal test during the first week of illness of 82 suspected cases of typhoid. RESULTS: The respective figures of positivity for PCR, blood culture and Widal test were 71.95%, 34.1%, and 36.5%. A control group of 20 healthy persons gave figures of 0%, 0%, and 33.3%, respectively. CONCLUSION: We conclude that this PCR-based technique is not only absolutely specific, but also very sensitive and, therefore, much superior to blood culture and Widal test for the early diagnosis of typhoid. PMID- 17277538 TI - Bilateral empyema thoracis treated by staged thoracotomies. PMID- 17277539 TI - Hodgkin's disease presenting with multiple cervical sinuses and abscess formation. PMID- 17277540 TI - Anaplastic KI-1 (CD30) positive large cell lymphoma of the stomach mimicking Hodgkin's disease: A case report and review of the literature. PMID- 17277542 TI - Placental teratoma: A case report and review of the literature. PMID- 17277541 TI - Cryptophthalmos syndrome (Fraser syndrome) with cardiac findings in a Saudi newborn. PMID- 17277543 TI - Acute aseptic meningitis associated with administration of immunoglobulin in children: A case report and review of the literature. PMID- 17277544 TI - Overweight status: Body image and weight control beliefs and practices among female college students. PMID- 17277546 TI - Volatile substance abuse: Experience from Al Amal Hospital, Jeddah. PMID- 17277545 TI - Hyperplastic, premalignant and malignant lesions of the prostate gland. PMID- 17277547 TI - Lack of reinfection after Helicobacter pylori eradication in duodenal ulcer disease: A prospective study from Turin, Italy. PMID- 17277548 TI - The clinical pattern and complications of severe malaria in the Gizan region of Saudi Arabia. PMID- 17277549 TI - Can ear lobe thickness be used for estimation of gestational age? PMID- 17277550 TI - Kikuchi disease presenting as anemia. PMID- 17277551 TI - Recognition and treatment of mental disorders in primary health care. PMID- 17277552 TI - Reply: Recognition and treatment of mental disorders in primary health care. PMID- 17277553 TI - Acute hydrops of the gallbladder in a 10-year-old boy with infectious hepatitis. PMID- 17277554 TI - Reply: Cancer patients' awareness of their disease and prognosis. PMID- 17277557 TI - A less invasive approach for ruptured aneurysm with intracranial hematoma: coil embolization followed by clot evacuation. AB - OBJECTIVE: The presence of an intracerebral hematoma from a ruptured aneurysm is a negative predictive factor and it is associated with high morbidity and mortality rates even though clot evacuation followed by the neck clipping is performed. Endovascular coil embolization is a useful alternative procedure to reduce the surgical morbidity and mortality rates. We report here on our experiences with the alternative option of endovascular coil placement followed by craniotomy for clot evacuation. MATERIALS AND METHODS: Among 312 patients who were admitted with intracerebral subarachnoid hemorrhage during the recent three years, 119 cases were treated via the endovascular approach. Nine cases were suspected to show aneurysmal intracerebral hemorrhage (ICH) on CT scan and they underwent emergency cerebral angiograms. We performed immediate coil embolization at the same session of angiographic examination, and this was followed by clot evacuation. RESULTS: Seven cases showed to have ruptured middle cerebral artery (MCA) aneurysms and two cases had internal carotid artery aneurysms. The clinical status on admission was Hunt-Hess grade (HHG) IV in seven patients and HHG III in two. Surgical evacuation of the clot was done immediately after the endovascular coil placement. The treatment results were a Glasgow Outcome Scale score of good recovery and moderate disability in six patients (66.7%). No mortality was recorded and no procedural morbidity was incurred by both the endovascular and direct craniotomy procedures. CONCLUSION: The results indicate that the coil embolization followed by clot evacuation for the patients with aneurysmal ICH may be a less invasive and quite a valuable alternative treatment for this patient group, and this warrants further investigation. PMID- 17277558 TI - Assessment of lymph node metastases by contrast-enhanced MR imaging in a head and neck cancer model. AB - OBJECTIVE: We wanted to investigate the accuracy of contrast-enhanced MR imaging for the detection of lymph node metastases in a head and neck cancer rabbit model. MATERIALS AND METHODS: The metastatic lymph node model we used was created by inoculating VX2 tumors into the auricles of six New Zealand White rabbits. T1 weighted MR images were obtained before and after injecting gadopentetate dimeglumine at three weeks after tumor cell inoculation. The sizes, signal intensity ratios (i.e., the postcontrast signal intensities of the affected nodes relative to the adjacent muscle) and the enhancement patterns of 36 regional lymph nodes (parotid and caudal mandibular nodes) were evaluated on MR images and then compared with the histopathologic findings. RESULTS: No statistical difference was found between the sizes of 12 metastatic (10.5+/-3.2 mm) and 24 hyperplastic (8.0+/-3.6 mm) lymph nodes (p > 0.05). On the contrast-enhanced T1 weighted MR images, nine metastatic and four hyperplastic lymph nodes had peripheral high and central low signal intensity, whereas three metastatic and 20 hyperplastic lymph nodes had homogeneous high signal intensity. Using a signal intensity ratio less than one as a diagnostic criterion for a metastatic lymph node, the sensitivity, specificity and positive and negative predictive values of the enhanced MR images were 75% (9/12), 83% (20/24), 69% (9/13) and 87% (20/23), respectively, with areas under receiver-operating-characteristic curve values of 0.81. CONCLUSION: This experimental study confirms that metastatic and hyperplastic lymph nodes can be differentiated using MR images on the basis of the contrast uptake patterns, but that they cannot be differentiated using any particular size criteria. PMID- 17277559 TI - Assessment of the right ventricular function and mass using cardiac multi detector computed tomography in patients with chronic obstructive pulmonary disease. AB - OBJECTIVE: We wanted to assess the relationship between measurements of the right ventricular (RV) function and mass, with using cardiac multi-detector computed tomography (MDCT) and the severity of chronic obstructive pulmonary disease (COPD) as determined by the pulmonary function test (PFT). MATERIALS AND METHODS: Measurements of PFT and cardiac MDCT were obtained in 33 COPD patients. Using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, the patients were divided into three groups according to the severity of the disease: stage I (mild, n = 4), stage II (moderate, n = 15) and stage III (severe, n = 14). The RV function and the wall mass were obtained by cardiac MDCT. The results were compared among the groups using the Student-Newman-Keuls method. Pearson's correlation was used to evaluate the relationship between the right ventricular ejection fraction (RVEF) and the wall mass results with the PFT results. P-values less than 0.05 were considered statistically significant. RESULTS: The RVEF and mass were 47+/-3% and 41+/-2 g in stage I, 46+/-6% and 46+/-5 g in stage II, and 35+/-5% and 55+/-6 g in stage III, respectively. The RVEF was significantly lower in stage III than in stage I and II (p < 0.01). The RV mass was significantly different among the three stages, according to the disease severity of COPD (p < 0.05). The correlation was excellent between the MDCT results and forced expiratory volume in 1 sec (r = 0.797 for RVEF and r = -0.769 for RV mass) and forced expiratory volume in 1 sec to the forced vital capacity (r = 0.745 for RVEF and r = -0.718 for RV mass). CONCLUSION: Our study shows that the mean RV wall mass as measured by cardiac MDCT correlates well with the COPD disease severity as determined by PFT. PMID- 17277560 TI - Nodular ground-glass opacities on thin-section CT: size change during follow-up and pathological results. AB - OBJECTIVE: To evaluate the inter-group differences in growth and the pathological results of nodular ground-glass opacities (GGOs) according to their size and focal solid portions. MATERIALS AND METHODS: Ninety-six nodular GGOs in 55 individuals followed by CT for at least one month from an initial chest CT were included. Forty nodular GGOs in 30 individuals were pathologically confirmed to be: adenocarcinoma (n = 15), bronchioloalveolar carcinoma (BAC) (n = 11), atypical adenomatous hyperplasia (AAH) (n = 8), focal interstitial fibrosis (n = 5) and aspergillosis (n = 1). Lesions were categorized based on high-resolution CT findings: pure nodular GGO (PNGGO) < or = 10 mm, PNGGO > 10 mm, mixed nodular GGO (MNGGO) < or = 10 mm, and MNGGO > 10 mm. In each group, the change in size during the follow-up period, the pathological results and the rate of malignancy were evaluated. RESULTS: Three MNGGO lesions, and none of the PNGGO, grew during the follow-up period. Resected PNGGOs < or = 10 mm were AAH (n = 6), BAC (n = 5), and focal interstitial fibrosis (n = 1). Resected PNGGOs > 10 mm were focal interstitial fibrosis (n = 4), AAH (n = 2), BAC (n = 2), and adenocarcinoma (n = 2). Resected MNGGOs < or = 10 mm were adenocarcinoma (n = 2), and BAC (n = 1). Resected MNGGOs > 10 mm were adenocarcinoma (n = 11), BAC (n = 3), and aspergillosis (n = 1). CONCLUSION: Mixed nodular GGOs (MNGGOs) had the potential for growth; most were pathologically adenocarcinoma or BAC. By contrast, PNGGOs were stable for several months to years; most were AAH, BAC, or focal interstitial fibrosis. PMID- 17277561 TI - MRI of the breast for the detection and assessment of the size of ductal carcinoma in situ. AB - OBJECTIVE: The aim of the study was to compare the accuracy of magnetic resonance imaging (MRI) and mammography for the detection and assessment of the size of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: The preoperative contrast enhanced MRI and mammography were analyzed in respect of the detection and assessment of the size of DCIS in 72 patients (age range: 30-67 years, mean age: 47 years). The MRI and mammographic measurements were compared with the histopathologic size with using the Pearson's correlation coefficients and the Mann-Whitney u test. We evaluated whether the breast density, the tumor nuclear grade, the presence of comedo necrosis and microinvasion influenced the MRI and mammographic size estimates by using the chi-square test. RESULTS: Of the 72 DCIS lesions, 68 (94%) were detected by MRI and 62 (86%) were detected by mammography. Overall, the Pearson's correlation of the size between MRI and histopathology was 0.786 versus 0.633 between mammography and histopathology (p < 0.001). MRI underestimated the size by more than 1 cm (including false negative examination) in 12 patients (17%), was accurate in 52 patients (72%) and overestimated the size by more than 1 cm in eight patients (11%) whereas mammography underestimated the size in 25 patients (35%), was accurate in 31 patients (43%) and overestimated the size in 16 patients (22%). The MRI, but not the mammography, showed significant correlation for the assessment of the size of tumor in noncomedo DCIS (p < 0.001 vs p = 0.060). The assessment of tumor size by MRI was affected by the nuclear grade (p = 0.008) and the presence of comedo necrosis (p = 0.029), but not by the breast density (p = 0.747) or microinvasion (p = 0.093). CONCLUSION: MRI was more accurate for the detection and assessment of the size of DCIS than mammography. PMID- 17277562 TI - CT diagnosis of Fitz-Hugh and Curtis syndrome: value of the arterial phase scan. AB - OBJECTIVE: We wanted to evaluate the role of the arterial phase (AP) together with the portal venous phase (PP) scans in the diagnosis of Fitz-Hugh-Curtis syndrome (FHCS) with using computed tomography (CT). MATERIALS AND METHODS: Twenty-five patients with FHCS and 25 women presenting with non-specifically diagnosed acute abdominal pain and who underwent biphasic CT examinations were evaluated. The AP scan included the upper abdomen, and the PP scan included the whole abdomen. Two radiologists blindly and retrospectively reviewed the PP scans first and then they reviewed the AP plus PP scans. The diagnostic accuracy of FHCS on each image set was compared for each reader by analyzing the area under the receiver operating characteristic curve (Az). Weighted kappa (wk) statistics were used to measure the interobserver agreement for the presence of CT signs of the pelvic inflammatory disease (PID) on the PP images and FHCS as the diagnosis based on the increased perihepatic enhancement on both sets of images. RESULTS: The individual diagnostic accuracy of FHCS was higher on the biphasic images (Az = 0.905 and 0.942 for reader 1 and 2, respectively) than on the PP images alone (Az = 0.806 and 0.706, respectively). The interobserver agreement for the presence of PID on the PP images was moderate (wk = 0.530). The interobserver agreement for FHCS as the diagnosis was moderate on only the PP images (wk = 0.413), but it was substantial on the biphasic images (wk = 0.719). CONCLUSION: Inclusion of the AP scan is helpful to depict the increased perihepatic enhancement, and it improves the diagnostic accuracy of FHCS on CT. PMID- 17277563 TI - Transcatheter arterial embolization of nonvariceal upper gastrointestinal bleeding with N-butyl cyanoacrylate. AB - OBJECTIVE: To evaluate the clinical efficacy and safety of transcatheter arterial embolization (TAE) with N-Butyl Cyanoacrylate (NBCA) for nonvariceal upper gastrointestinal bleeding. MATERIALS AND METHODS: Between March 1999 and December 2002, TAE for nonvariceal upper gastrointestinal bleeding was performed in 93 patients. The endoscopic approach had failed or was discarded as an approach for control of bleeding in all study patients. Among the 93 patients NBCA was used as the primary embolic material for TAE in 32 patients (28 men, four women; mean age, 59.1 years). The indications for choosing NBCA as the embolic material were: inability to advance the microcatheter to the bleeding site and effective wedging of the microcatheter into the bleeding artery. TAE was performed using 1:1-1:3 mixtures of NBCA and iodized oil. The angiographic and clinical success rate, recurrent bleeding rate, procedure related complications and clinical outcomes were evaluated. RESULTS: The angiographic and clinical success rates were 100% and 91% (29/32), respectively. There were no serious ischemic complications. Recurrent bleeding occurred in three patients (9%) and they were managed with emergency surgery (n = 1) and with a successful second TAE (n = 2). Eighteen patients (56%) had a coagulopathy at the time of TAE and the clinical success rate in this group of patients was 83% (15/18). CONCLUSION: TAE with NBCA is a highly effective and safe treatment modality for nonvariceal upper gastrointestinal bleeding, especially when it is not possible to advance the microcatheter to the bleeding site and when the patient has a coagulopathy. PMID- 17277564 TI - Interventional management of malignant colorectal obstruction: use of covered and uncovered stents. AB - OBJECTIVE: We wanted to evaluate usefulness of uncovered stent in comparison with covered stent for the palliative treatment of malignant colorectal obstruction. MATERIALS AND METHODS: Covered (n = 52, type 1 and type 2) and uncovered (n = 22, type 3) stents were placed in 74 patients with malignant colorectal obstruction. Stent insertion was performed for palliative treatment in 37 patients (covered stent: n = 23 and uncovered stent: n = 14). In the palliative group, the data on the success of the procedure, the stent patency and the complications between the two groups (covered versus uncovered stents) were compared. RESULTS: The technical success rate was 89% (33/37). Symptomatic improvement was achieved in 86% (18/21) of the covered stent group and in 92% (11/12) of the uncovered stent group patients. The period of follow-up ranged from three to 319 days (mean period: 116+/-85 days). The mean period of stent patency was 157+/-33 days in the covered stent group and 165+/-25 days in the uncovered stent group. In the covered stent group, stent migration (n = 11), stent fracture (n = 2) and poor expansion of the stent (n = 2) were noted. In the uncovered stent group, tumor ingrowth into the stents (n = 3) was noted. CONCLUSION: Self-expanding metallic stents are effective for relieving malignant colorectal obstruction. The rate of complications is lower in the uncovered stent group than in the covered stent group. PMID- 17277565 TI - Peliosis hepatis with hemorrhagic necrosis and rupture: a case report with emphasis on the multi-detector CT findings. AB - We report here on an uncommon case of peliosis hepatis with hemorrhagic necrosis that was complicated by massive intrahepatic bleeding and rupture, and treated by emergent right lobectomy. We demonstrate the imaging findings, with emphasis on the triphasic, contrast-enhanced multidetector CT findings, as well as reporting the clinical outcome in a case of peliosis hepatis with fatal hemorrhage. PMID- 17277566 TI - Hepatic parasitic abscess caused by clonorchiasis: unusual CT findings of clonorchiasis. AB - Clonorchiasis is caused by a chronic infestation of liver flukes, Clonorchis sinensis, and these reside mainly in the medium- and small-sized intrahepatic bile ducts. Therefore, diffuse, uniform, minimal or mild dilatation of these bile ducts, particularly in the periphery, without dilatation of the extrahepatic bile duct is the typical finding on several imaging modalities. We report here on the CT findings of an unusual case of hepatic parasitic abscess that was caused by clonorchiasis; this malady mimicked cholangiocarcinoma, and there was no dilatation of the intrahepatic bile ducts. PMID- 17277567 TI - Magnetic resonance imaging of transient left ventricular apical ballooning related to emotional stress: a case report. AB - Transient left ventricular apical ballooning is characterized by transient wall motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of coronary arterial occlusion. A 66-year-old woman presented to the emergency department with chest pain that mimicked acute myocardial infarction. An aortogram showed akinesis from the mid to apical left ventricle with sparing of the basal segments. Four days later, she underwent MRI, which demonstrated characteristic apical contractile dysfunction, the same as the aortogram, without evidence of myocardial infarction on the MRI. Two weeks later, her symptoms were resolved and follow-up echocardiography showed normal ventricular function. PMID- 17277568 TI - CNS involvement in hemophagocytic lymphohistiocytosis: CT and MR findings. AB - Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by proliferation of benign histiocytes, and this commonly involves the liver, spleen, lymph nodes, bone marrow and central nervous system (CNS). We report here on the CT and MR imaging findings in a case of CNS HLH that showed multiple ring enhancing masses mimicking abscess or another mass on the CT and MR imaging. PMID- 17277569 TI - Diffusion-weighted MR imaging of unusual white matter lesion in a patient with Menkes disease. AB - We report here on the diffusion-weighted imaging of unusual white matter lesions in a case of Menkes disease. On the initial MR imaging, the white matter lesions were localized in the deep periventricular white matter in the absence of diffuse cortical atrophy. The lesion showed diffuse high signal on the diffusion-weighted images and diffuse progression and persistent hyperintensity on the follow up imaging. Our case suggests that the white matter lesion may precede diffuse cortical atrophy in a patient with Menkes disease. PMID- 17277570 TI - Study of the human visual cortex: direct cortical evoked potentials and stimulation. AB - The authors studied the visual cortex of 15 patients undergoing studies for medically intractable epilepsy. Although the subdural and strip electrode placement varied in each of these patients, there were enough electrodes over the visual cortex to complete studies involving evoked potentials and direct cortical stimulation. Visual evoked potentials were elicited using two check sizes (50 and 16 min) for pattern reversal studies, 50 min checks for on-off stimulation, 50 min checks for horizontal and vertical hemifields and simple flash for the VEP. These studies demonstrated that the pattern reversal and on-off stimuli caused very complex, multipotential waveforms in striate and vision associational cortex that do not resemble the response obtained at the scalp. Different volumes of visual cortex are activated by stimulation with 16 min checks, 50 min checks and simple flash. Flash activates the largest volume of visual cortex and it is likely that this finding is what makes this test of so little value clinically. Direct cortical stimulation shows that colored responses are generated primarily in the posterior striate cortex and inferior occipital lobe, while movement is primarily generated by the visual association cortex. No complex visual images were obtained by stimulation of either the striate cortex or visual association cortex. The brain mechanisms that lead to formed visual images remain to be identified. PMID- 17277571 TI - Interictal EEG in temporal lobe epilepsy in childhood. AB - The authors clarified the value of interictal discharges and verified which extratemporal regions may also show epileptiform activity in temporal lobe epilepsy (TLE) in childhood. Thirty consecutive patients aged 3 to 18 years (mean age = 12.16 years; 16 male) with TLE associated with hippocampal atrophy were studied. Each patient had 1 to 15 interictal EEG recordings (mean: 5.6; total = 192 EEGs). Video-EEG monitoring was performed in 20 patients. All patients had MRI. The findings were compared with a control group of 53 consecutive TLE adult outpatients with hippocampal atrophy. Each adult patient underwent 3 to 21 routine EEGs (mean: 10.67; total = 566). Interictal EEGs of children with TLE showed extratemporal epileptiform discharges more frequently than EEGs of adults with TLE. Frontal, parietal, and occipital discharges were more frequently seen in children (P < 0.05). These results suggest a close interaction between temporal and other cerebral regions in children with epilepsy and provide further evidence of the existence of neural networks. PMID- 17277572 TI - Incorporating abbreviated EEGs in the initial workup of patients who present to the emergency room with mental status changes of unknown etiology. AB - Patients frequently present to the emergency room (ER) with mental status changes without obvious cause. The EEG is underused in this population. The authors investigated whether an abbreviated EEG (AbEEG) can be incorporated in the early evaluation of these patients to provide useful information. A 5-minute AbEEG was performed using a preformed electrode placement system on 25 patients who presented to the ER with mental status changes of unknown cause. AbEEG findings were categorized as normal, showing diffuse abnormalities, focal abnormalities, electrographic seizures, or uninterpretable. Using retrospective chart review, the authors determined if the cause of mental status change was a diffuse encephalopathy or a nonneurologic event (DENNE), a focal brain abnormality, nonconvulsive status epilepticus (NCSE), psychogenic, or unknown, and if particular AbEEG findings were associated with specific causes of altered sensorium. The AbEEG identified NCSE in two patients who presented with new-onset seizures. The presence of diffuse slowing on the AbEEG was highly suggestive of mental status changes due to DENNE. AbEEGs can be successfully incorporated in the early evaluation of patients who present to the ER with mental status changes of unknown cause and provide useful information in this setting. PMID- 17277573 TI - Does the hippocampal atrophy correlate with the cortical theta power in elderly subjects with a range of cognitive impairment? AB - A previous study with a small sample (N = 39) showed a significant correlation between the cortical theta activity and the hippocampal volume in different stages of cognitive impairment in aged subjects. The recent study was aimed to replicate these results in a much bigger sample. The authors examined a sample of 121 right-handed subjects. The sample consisted of 37 healthy controls, 40 patients with questionable dementia, and 44 patients with mild dementia assessed by Clinical Dementia Rating. All subjects underwent EEG and brain MRI. Mean spectral power was calculated, and volume of hippocampal segments was measured. EEG theta power of the left and right hemisphere correlated significantly with the hippocampal volume on the left and right side in different stages of cognitive impairment. An increase of theta power was associated with decreased hippocampal volume. No other significant correlations were found for alpha or beta band power. No correlation was found between cortical theta and global brain volume. There seems to be a direct relationship between neuronal loss of the hippocampus and changed cortical theta activity for different stages of cognitive impairment in aged subjects. PMID- 17277574 TI - Human high frequency somatosensory evoked potential components are refractory to circadian modulations of tonic alertness. AB - The impact of vigilance states, such as sleep or arousal changes, on the high frequency (600 Hz) components (HFOs) of somatosensory evoked potentials (SEPs) is known. The present study sought to characterize the effects of circadian fluctuations of tonic alertness on HFOs in awake humans. Median nerve SEPs were recorded at four times during a 24-hour waking period. In parallel to the SEP recordings, a reaction-time (RT) task was performed to assess tonic alertness. Additionally, the spontaneous EEG was monitored. The low-frequency SEP component N20 and the early and late HFO parts did not change across the measurement sessions. In contrast, RTs were clearly prolonged at night and on the second morning. EEG also showed increased delta power at night. HFOs are sensitive to pronounced vigilance changes, such as sleep, but are refractory to fluctuations of tonic alertness. Tonic alertness is regarded to be the top-down cognitive control mechanism of wakefulness, whereas sleep is mediated by overwhelming bottom-up regulation, which seems apparently more relevant for, at least in part, subcortically triggered high-frequency burst generation in the ascending somatosensory system. PMID- 17277575 TI - Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. AB - The H-coils are a novel development in transcranial magnetic stimulation (TMS), designed to achieve effective stimulation of deep neuronal regions without inducing unbearable fields cortically, thus broadly expanding the potential feasibility of TMS for research and for treating various neurologic disorders. This study compared the field distribution of two H-coil versions, termed H1 and H2, and of a standard figure-of-eight coil. Three-dimensional electrical field distributions of the H1 and H2-coils, designed for effective stimulation of prefrontal regions, and of a standard figure-8 coil, were measured in a head model filled with physiologic saline solution. With stimulator output at 120% of the hand motor threshold, suprathreshold field is induced by the H1-coil at lateral and medial frontal regions at depths of up to 4 to 5 cm, and by the H2 coil at medial prefrontal regions up to 2 to 3 cm, and at lateral frontal regions up to 5 to 6 cm. The figure-8 coil induced suprathreshold field focally under the coil's central segment, at depths of up to 1.5 cm. The ability of the H-coils to stimulate effectively deeper neuronal structures is obtained at the cost of a wider electrical field distribution in the brain. However, the H-coils enable simultaneous stimulation of several brain regions, whereas the depth penetration in each region can be controlled either by adjusting the stimulator output, and/or by varying the distance between various coil elements and the skull. PMID- 17277576 TI - Intraoperative risk of seizures associated with transient direct cortical stimulation in patients with symptomatic epilepsy. AB - Direct cortical stimulation--either with the 60-Hz stimulation or the train-of five technique--is commonly agreed on being the gold standard for intraoperative mapping of the motor cortex and the motor pathways but may result in an intraoperative seizure. The occurrence of intraoperative stimulation associated seizures with respect to symptomatic epilepsy was evaluated in a group of 129 patients undergoing tumor resection within the central region. Data were reviewed with respect to the frequency of seizures with both stimulation techniques and symptomatic epilepsy. Direct stimulation of the motor cortex was performed with a train of five consecutive pulses, an interstimulus interval of 4 ms, an individual pulse width of 0.5 ms, and 40 mA stimulation intensity at maximum. In 1 of 63 patients (1.6%) presenting with symptomatic epilepsy, a stimulation associated seizure occurred, and 1 of the other 66 patients (1.5%) had a seizure (n.s., not significant). In the literature, stimulation associated seizures are reported in 1.2% with the train-of-five technique and significantly more frequently in 9.5% with the 60-Hz technique (P < 0.001). In summary, there is no increased risk of the occurrence of stimulation-associated seizures during surgery for patients with symptomatic epilepsy compared with those patients without. PMID- 17277577 TI - Magnetic brainstem stimulation of the facial nerve. AB - Electrophysiological evaluation of cranial nerves provides information on its functional aspects and may be a valuable adjunct to imaging. In 10 normal subjects, we used transcranial magnetic stimulation with a double cone coil at the posterior head region to obtain orbicularis oris motor evoked potentials. Our findings suggest activation of descending facial fibers proximal to brainstem motoneurons. This method is advocated as an adjunct in the electrodiagnostic workup of facial nerve dysfunction. PMID- 17277578 TI - Motor evoked potentials after transcranial magnetic stimulation support hypothesis of coexisting central mechanism in obstetric brachial palsy. AB - Six infants with obstetric brachial palsy, ranging from 4 to 7 months of age, were investigated. One was suspected of having extensive brachial plexus lesions and five were suspected of having a unilateral lesion of both roots C5 and C6. All were referred to our center to investigate the possibility for reconstructive surgery. In all infants, even at this age, transcranial magnetic stimulation resulted in motor evoked potentials (MEP) in the biceps (in one, in the brachioradial) muscles. Averaging could not be done because of the intraindividual variation in latency. The MEP was easier to recognize if evoked when the infant had the arm bent. In all five infants suspected of upper brachial plexus lesion with avulsion of both roots C5 and C6 and/or complete rupture of the upper trunk, proven in four, an MEP on the lesioned side could be evoked. Combined with earlier investigations showing (almost) normal EMG and somatosensory evoked potentials in infants with upper plexus lesion, this leads us to the conclusion that the paralysis of these infants cannot only be attributed to the peripheral axonal damage alone but that central plasticity must also play an important role. As this is a slow process, some infants might not yet be able to use the paralytic muscles. Some theoretic issues are discussed. PMID- 17277579 TI - Motor unit action potential duration, I: variability of manual and automatic measurements. AB - The aim of this work is to analyze the variability in manual measurements of motor unit action potential (MUAP) duration and to evaluate the effectiveness of well-known algorithms for automatic measurement. Two electromyographists carried out three independent duration measurements of a set of 240 MUAPs. The intraexaminer and interexaminer variabilities were analyzed by means of the Gage Reproducibility and Repeatability method. The mean of the three closest manually marked positions was considered the gold standard of the duration markers positions (GSP). The results of four well-known automatic methods for estimating MUAP duration were compared to the GSP. Manual measurements of duration showed a lot of variability, with the combined intraoperator and interoperator variability greater than 30%. The greatest difference between manual positions was 11.2 ms. The mean differences between the GSP and those obtained with the four automatic methods ranged between 0.6 and 8.5 ms. Both manual and automatic measurements of MUAP duration show a high degree of variability. More precise methods are needed to improve the accuracy and reliability of the estimates of this parameter. PMID- 17277580 TI - Motor unit action potential duration, II: a new automatic measurement method based on the wavelet transform. AB - The aim of this work is to present and evaluate a new algorithm, based on the wavelet transform, for the automatic measurement of motor unit action potential (MUAP) duration. A total of 240 MUAPs were studied. The waveform of each MUAP was wavelet-transformed, and the start and end points were estimated by regarding the maxima and minima points in a particular scale of the wavelet transform. The results of the new method were compared to the gold standard of duration marker positions obtained by manual measurement. The new method was also compared to a conventional algorithm, which we had found to be best in a previous comparative study. To evaluate the new method against manual measurements, the dispersion of automatic and manual duration markers were analyzed in a set of 19 repeatedly recorded MUAPs. The differences between the new algorithm's marker positions and the gold standard of duration marker positions were smaller than those observed with the conventional method. The dispersion of the new algorithm's marker positions was slightly less than that of the manual one. Our new method for automatic measurement of MUAP duration is more accurate than other available algorithms and more consistent than manual measurements. PMID- 17277581 TI - Sympathetic skin response and axon count in carpal tunnel syndrome. AB - The aim of this study was to determine the sensitivity of sympathetic skin response (SSR) in evaluating autonomic involvement in carpal tunnel syndrome (CTS) while simultaneously showing the axonal loss by motor unit number estimation (MUNE). Bilateral SSR were recorded by suprasternal stimulus in 50 hands of 31 patients and compared with 50 hands of 25 healthy volunteers. The groups were examined for sympathetic symptoms and sympathetic symptom scores (SSS) were determined. Axon count was performed on the abductor pollicis brevis (APB) muscle by using the MUNE method (with incremental technique) in both groups. There was no SSR difference between groups, although a significant difference was found for SSS. No relationships were found between SSR parameters and SSS or the electrophysiologic stage. MUNE of the APB muscle was significantly lower in CTS group and there was a negative correlation between MUNE and the electrophysiologic stage. The comparison of the MUNE and the amplitude of median compound muscle action potential indicated that MUNE is a highly sensitive method of determining severity in patients with CTS. In evaluating autonomic involvement in CTS, SSR does not seem to be a sensitive method. MUNE is a good indicator of motor reserve and can be helpful when following the treatment and prognosis of CTS in clinical practice. PMID- 17277582 TI - Central processing of acute muscle pain in chronic low back pain patients: an EEG mapping study. AB - The presence of perceptual sensitization and related brain responses was examined in 14 chronic low back pain (CLBP) patients and 13 healthy controls comparable in age and sex. Multichannel EEG recordings and pain ratings were obtained during the presentation of 800 painful electrical intramuscular and intracutaneous stimuli each to the left m. erector spinae and the left m. extensor digitorum. Perception and pain thresholds were not significantly different between the two groups, though patients showed significantly more perceptual sensitization. Across all stimulation conditions, a larger EEG component 80 milliseconds after stimulation was observed in the CLBP group. No significant group differences were found for the N150. The component 260 milliseconds after stimulus onset was significantly smaller in the CLBP group. N80, N150, and perceptual sensitization were significantly positively correlated. These results indicate enhanced perceptual sensitization and enhanced processing of the sensory-discriminative aspect of pain, as expressed in the N80 component, in CLBP patients. This may be one neurophysiologic basis of sensitization and the chronicity process. The lower P260 component in the patients may be explained in terms of tonic pain inhibiting phasic pain or may be related to the affective distress observed in this patient group. PMID- 17277583 TI - The prognostic value of ventilatory efficiency with beta-blocker therapy in heart failure. AB - PURPOSE: Beta-blockade (BB) has been shown to improve outcomes among patients with heart failure (HF). The impact this pharmacological approach has on the prognostic information gained from cardiopulmonary exercise testing (CPX) is, however, unclear. METHODS: Four hundred seventeen subjects diagnosed with HF underwent CPX. The numbers of subjects prescribed and not prescribed a BB agent were 167 and 250, respectively. Subjects were tracked for cardiac-related mortality after CPX. RESULTS: Values are reported for the no-BB versus the BB group throughout. Age (57.9 +/- 13.3 vs 55.6 +/- 12.5), peak VO2 (16.2 +/- 5.7 vs 16.5 +/- 5.5 mL x kg(-1) x min(-1)), VE/VCO2 slope (34.2 +/- 9.0 vs 33.2 +/- 7.4), and peak RER (1.07 +/- 0.16 vs 1.05 +/- 0.14) were similar between groups (P > 0.05). Multivariate Cox regression analysis revealed that the VE/VCO2 slope was the superior predictor of death in both groups (chi-square: 71.9, P < 0.001; and 18.4, P < 0.001). The optimal threshold values for VE/VCO2 slope in the no-BB and BB groups were 36.0 and 34.3, respectively. CONCLUSIONS: The results of the present study indicate that BB does not alter the prognostic value/characteristics of the VE/VCO2 slope. Findings from previous investigations examining the prognostic significance of CPX predominantly using HF groups not receiving a BB agent may, therefore, still be applicable in modern-day clinical practice. PMID- 17277585 TI - Physical activity, diet, and incident diabetes in relation to an ADRA2B polymorphism. AB - PURPOSE: The 12Glu9 polymorphism of the alpha2B-adrenergic receptor gene may impair insulin secretion and modify the effects of a lifestyle intervention on the risk of type 2 diabetes, but the interaction with specific lifestyle components is unknown. We assessed the associations of leisure-time physical activity (LTPA), dietary changes, and weight loss on the risk of type 2 diabetes according to the 12Glu9 polymorphism in 481 participants of the Finnish Diabetes Prevention Study. METHODS AND RESULTS: The lifestyle intervention decreased the risk of diabetes in 9Glu carriers (9Glu9, intervention vs control, relative risk (RR) = 0.23, 95% confidence interval (CI) 0.09-0.62), but not in 12Glu12 homozygotes. In the combined intervention and control groups, increased total LTPA as estimated with a questionnaire decreased the risk of diabetes in 12Glu carriers (12Glu12, upper vs lower third, RR = 0.12, 95% CI 0.03-0.53) but not in 9Glu9 homozygotes (P for the interaction 0.033). In contrast, favorable dietary changes, estimated using a dietary score, reduced the risk of diabetes in those with the 9Glu9 genotype (upper vs lower third, RR = 0.21, 95% CI 0.06-0.75) but not in those with the 12Glu allele. Weight loss significantly decreased the risk of diabetes only in 12Glu carriers. CONCLUSION: Increased LTPA decreased the risk of type 2 diabetes more in those with the 12Glu allele of the ADRA2B gene, whereas dietary changes may have mediated the greater risk reduction of the lifestyle intervention in 9Glu homozygotes. PMID- 17277584 TI - Maximal strength training of the legs in COPD: a therapy for mechanical inefficiency. AB - PURPOSE: A diminished mechanical efficiency (work/O2 consumed) accompanies chronic obstructive pulmonary disease (COPD), and increased mechanical efficiency has been attained by maximal strength training (MST) with an emphasis on the maximal rate of force mobilization in the concentric phase in healthy subjects. This study combined these observations and evaluated the impact of short-term MST on patients with COPD. METHODS: Twelve patients with COPD (FEV1 = 1.1 +/- 0.1) were pretested and then randomly assigned to either an MST group (N = 6) or a normal activity control group (N = 6). Within each MST training session (three times per week for 8 wk), patients performed four sets of seated leg presses with a focus on the rate of force development at an intensity that only allowed the performance of five repetitions. RESULTS: Patients who performed MST significantly improved their rate of force development (105 +/- 22.8%), mechanical efficiency (32 +/- 7%), and FEV1 (21.5 +/- 6.8%), whereas these variables were unchanged in the controls. Neither group changed either peak oxygen consumption (VO2peak) or body mass. CONCLUSION: In combination with the observed improvement in FEV1, these data certainly support the therapeutic role for MST in the treatment of COPD. PMID- 17277586 TI - Muscular strength, aerobic fitness, and metabolic syndrome risk in Flemish adults. AB - PURPOSE: To investigate the association of muscular strength and aerobic fitness with a continuous metabolic syndrome risk score in male and female adults. METHODS: This cross-sectional study included 1019 (571 men) Flemish adults, aged 18-75. Muscular strength was evaluated by measuring isometric knee extension and flexion peak torque, using a Biodex System Pro 3 dynamometer. Aerobic fitness was quantified as VO2peak and was determined during a maximal cycle ergometer exercise test. Both strength and aerobic fitness were scaled for differences in FFM, using allometric analyses. A validated metabolic syndrome risk score that was based on waist circumference, triglycerides, blood pressure, fasting plasma glucose, and HDL cholesterol was used. Metabolic syndrome risk score, strength, and aerobic fitness were analyzed as continuous variables using multiple linear regression. RESULTS: Metabolic syndrome risk was inversely associated with strength, independently of aerobic fitness, and after adjustment for age, height, education level, smoking status, and dietary intake in women (beta = -0.172, P < 0.001). In men, however, adjustment for aerobic fitness attenuated the inverse association between strength and metabolic syndrome risk (beta = -0.044, P > 0.05). Independently of strength, aerobic fitness was inversely associated with metabolic syndrome risk (men: beta = -0.309, P < 0.001; women: beta = -0.208, P < 0.001). Furthermore, independent associations were found for strength and aerobic fitness with several individual metabolic syndrome risk factors in women, and most of these associations were only partially mediated by central and general adiposity indicators. CONCLUSION: Although cross-sectional, the present results support inclusion of strength training in addition to aerobic exercise in physical activity recommendations for women, because both types of activity might show additional effects in reducing the risk of the metabolic syndrome. PMID- 17277587 TI - Prevalence of preseason conditioning among high school athletes in two spring sports. AB - PURPOSE: To determine the prevalence and predictors of preseason conditioning among high school athletes. METHODS: Cross-sectional survey of 451 high school athletes participating on girls and boys track and boys soccer teams in five public high schools in Seattle, WA, spring 2005. Questions were modified from validated surveys of physical activity for adolescents. The main outcome measure was meeting criteria for adequate preseason conditioning, which specify a combination of aerobic conditioning (vigorous exercise for at least 300 min x wk( 1)) and stretching and strengthening exercises (at least three times a week for any duration). Log-binomial regression was performed to examine factors associated with preseason conditioning. RESULTS: The majority of athletes met the criteria for each of the components (59% for aerobic conditioning, 62% for stretching, 63% for strengthening). As defined by meeting the criteria for all three components, 33% of the athletes had adequate preseason conditioning. Of those athletes meeting criteria for all three components, the majority reported at least 1 month of conditioning to prepare for the season. Varsity athletes were more likely to meet the preseason conditioning criteria compared with junior varsity athletes (38 vs 25%, prevalence ratio 1.5, 95% CI 1.0-2.1). Athletes who reported help with conditioning from a coach were twice as likely to have adequate preseason conditioning compared with those who did not receive help from a coach (45 vs 23%, prevalence ratio 1.8, 95% CI 1.3-2.4). CONCLUSION: The majority of athletes in this study did meet criteria for each individual conditioning component (aerobic, stretching, strengthening), but only a minority met all three criteria. These findings highlight the need for school- or coach sponsored involvement to ensure that all athletes engage in comprehensive preseason conditioning programs. PMID- 17277588 TI - Estradiol and tamoxifen reverse ovariectomy-induced physical inactivity in mice. AB - Decreased physical activity and increased body mass are associated with estrogen deficiency. PURPOSE: To determine whether estrogen or the estrogen analog, tamoxifen, could reverse those detrimental effects after surgical ovariectomy in mice. METHODS: Ten-week-old C57BL/6 mice were sham operated (sham, N = 6) or ovariectomized (OVX, N = 9). After 4 wk of voluntary wheel running, placebo (OVX P) or 17beta-estradiol (OVX-E2) pellets were implanted and the mice ran an additional 4 wk. A second study followed in which mice received placebo, 17beta estradiol, or tamoxifen (OVX-Tam) simultaneously with ovariectomies. Distances run per 24 h and body masses were analyzed by two-way ANOVA with repeated measures. RESULTS: During the initial 4 wk, OVX mice ran approximately 80% less and had approximately 20% greater body masses compared with sham mice (P < 0.001). Estradiol replacement quickly reversed the inactivity as OVX-E2 mice increased their running from 1.9 +/- 0.3 km x 24 h(-1) to 6.9 +/- 0.7 km within a week of replacement, which was equivalent to shams (8.1 +/- 0.7 km), whereas OVX P mice ran only 0.5 +/- 0.2 km (P < 0.01). OVX-E2 mice tended to maintain body mass after estradiol replacement, whereas the OVX-P mice continued to increase mass. OVX mice that received tamoxifen had high running activity, approximately 9 km x 24 h(-1), and maintained body mass. CONCLUSION: The removal of ovarian hormones caused mice to become inactive and gain body mass. Hormone therapy in the form of 17beta-estradiol or tamoxifen rapidly stimulated voluntary wheel running and reversed body mass gains, indicating that estrogen receptor binding was involved in regulating physical activity. PMID- 17277589 TI - Delayed blood reoxygenation following maximum voluntary contraction. AB - PURPOSES: To characterize the total hemoglobin concentration ([THb]) and oxyhemoglobin saturation (%HbO2) time courses after brief dorsiflexion maximal voluntary contractions (MVC) and to determine whether these responses varied by gender. METHODS: Eighteen healthy, moderately physically active subjects (nine male) lay supine and performed two or more 3-s dorsiflexion MVC. [THb] and %HbO2 were measured continuously in the tibialis anterior muscle using near-infrared spectroscopy (NIRS). The data from 0 to 150 s postcontraction were analyzed using single- and multicomponent exponential models. RESULTS: The mean (standard error) precontraction [THb] and %HbO2 values were 78.5 (7.3) microM and 65.0 (0.8) %, respectively, and decreased during the contraction. After the contraction, [THb] grew exponentially, characterized by amplitude (A), 8.7 (1.3) microM; time delay (TD), 0.2 (0.2) s, and time constant (tau), 5.9 (0.6) s. Fifteen subjects had a secondary decay phase characterized by A, 1.9 (0.7) microM; TD, 59.2 (6.4) s; and tau, 12.4 (2.3) s. Eight subjects experienced an initial decay in %HbO2, characterized by A, 1.8 (0.8) %; TD, 0.0 (0) s; and tau, 4.2 (0.3) s. Then, %HbO2 grew exponentially, being characterized by A, 7.9 (0.9) %; TD, 10.1 (1.0) s; and tau, 9.7 (2.0) s. Finally, in 16 subjects, there was a secondary decay phase, characterized by A, 2.6 (0.4) %; TD, 54.4 (7.5) s; and tau, 18.9 (2.6) s. There were no gender differences in any kinetic parameter. CONCLUSIONS: There are three phases to the post-MVC oxygen supply-demand coupling: 1) rising oxygen demand relative to supply; 2) rising oxygen supply relative to demand; and 3) restoration of precontraction oxygen supply-demand matching. These processes are unaffected by gender. PMID- 17277590 TI - Muscle deoxygenation and neural drive to the muscle during repeated sprint cycling. AB - PURPOSE: To investigate muscle deoxygenation and neural drive-related changes during repeated cycling sprints in a fatiguing context. METHODS: Nine healthy male subjects performed a repeated-sprint test (consisting of 10 x 6-s maximal sprints interspaced by 30 s of recovery). Oxygen uptake was measured breath-by breath; muscle deoxygenation of the vastus lateralis was assessed continuously using the near-infrared spectroscopy technique. Surface electromyograms (RMS) of both vastus lateralis and biceps femoris were also recorded. Furthermore, before and after the repeated-sprint test, the percentage of muscle activation by voluntary drive (twitch-interpolated method) was measured during a maximal voluntary contraction. RESULTS AND DISCUSSION: Consistent with previous research, our data showed a significant power decrement during repeated-sprint exercise. There was also a progressive muscle deoxygenation, but our data showed that the ability of the subjects to use available O2 throughout the entire repeated-sprint test was well preserved. Our data displayed a significant decrement in the RMS activity during the acceleration phase of each sprint across the repeated-sprint exercise. Moreover, decrement in motor drive was confirmed after exercise by a significant decrease in both percentage of voluntary activation and RMS/M-wave ratio during a maximal voluntary contraction. CONCLUSION: In this experimental design, our findings suggest that the ability to repeat short-duration (6 s) sprints was associated with the occurrence of both peripheral and central fatigue. PMID- 17277591 TI - LeuCAM and reactive oxygen species during long-term exercise combined with sleep and energy deficiency. AB - INTRODUCTION: During the Norwegian military ranger-training course, cadets are exposed to prolonged physical exercise combined with sleep-, energy-, and food deficiency. The open-window postexercise hypothesis indicates that after hard physical activity, there is an increased risk of contracting infectious diseases. PURPOSE: The purpose of the present study was to determine leukocyte reactive oxygen species (ROS) levels, total antioxidant status (TAS), leukocyte expression of the cell adhesion molecules CD62L and CD11b, and plasma levels of soluble adhesion molecule L-selectin before, during, and in the recovery phase of a military ranger-training course. METHODS: Ten cadets from the Norwegian Military Academy were recruited to the study. Flow cytometry was used to study the intracellular levels of ROS in leukocytes (basally, as well as after in vitro stimulation with phorbol myristate acetate (PMA)), applying the probes dihydroethidium (DHE) and dihydrorhodamine 123 (DHR) and the leukocyte expression of adhesion molecules CD62L and CD11b. ELISA was used to assess the plasma levels of soluble L-selectin, and TAS in plasma was measured using the ABTS+ reduction assay kit. RESULTS: The basal levels of ROS as well as PMA-stimulated ROS in leukocytes declined gradually during the ranger-training course, being lowest on the last day (P < 0.05). The level of TAS increased (P < 0.01) during the course. A striking decrease (P < 0.001) was observed in leukocyte CD62L expression and was sustained even after 3 d of recovery. The leukocyte expression of CD11b remained unchanged. CONCLUSION: The ranger-training course leads to a partial exhaustion of the leukocyte ROS-generating machinery and to a nearly total extinguishing of leukocyte CD62L expression. These changes may support the open window hypothesis indicating reduced ability to combat microbial invasions before total restitution. PMID- 17277592 TI - Oxidative stress in half and full Ironman triathletes. AB - INTRODUCTION: Ultraendurance athletes who maintain a very high volume of exercise may, as a result of greater production of reactive oxygen species (ROS), be particularly susceptible to oxidative damage. PURPOSE: This study sought to examine and compare pre- and postrace markers of oxidative stress in ultraendurance athletes training for, and competing in, either a half or a full Ironman triathlon. METHODS: Resting and postexercise blood was sampled from 16 half Ironman triathletes, 29 full Ironman triathletes, and age-matched, relatively inactive controls. Blood was analyzed for markers of oxidative stress (malondialdehyde (MDA) concentration) and antioxidant status (glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD) activities). RESULTS: Compared with controls, the half Ironman triathletes had significantly (P < 0.001) higher erythrocyte GPX activity at rest, whereas the Ironman triathletes had significantly (P < 0.05) lower resting plasma MDA and significantly (P < 0.05) greater resting activities of GPX and CAT compared with controls. As a result of the half Ironman triathlon, there was a significant (P < 0.05) increase in MDA and significant (P < 0.05) decreases in erythrocyte GPX, SOD, and CAT activities. These changes also occurred in response to the Ironman triathlon; MDA significantly (P < 0.05) increased, and there were significant (P < 0.001) decreases in GPX, CAT, and SOD activities. Users of antioxidant supplements in both the half and full Ironman races had significantly (P < 0.05) elevated MDA after races compared with nonsupplementers. CONCLUSION: The present investigation indicates that training for and competing in half and full Ironman triathlons has different effects on erythrocyte antioxidant enzyme activities and oxidative stress. PMID- 17277593 TI - Postexercise myostatin and activin IIb mRNA levels: effects of strength training. AB - PURPOSE: Muscle hypertrophy is likely to result from the cumulative effects of repeated bouts of resistance exercise (RE) on postexercise molecular responses. Therefore, we determined muscle growth- and regeneration-related mRNA expression in response to a single RE bout both before and after a strength-training (ST) period. By means of this novel longitudinal setting, we examined whether postexercise gene expression at the transcriptional level is different in the trained and untrained state. METHODS: Eleven untrained healthy older men and 11 controls (age 62.3 +/- 6.3 yr) volunteered as subjects. Muscle biopsies from the vastus lateralis muscle were taken at rest and 1 and 48 h after five sets of 10 repetition leg press RE both before and after 21 wk of supervised ST. RESULTS: Myostatin and myogenin mRNA expression, determined by real-time RT-PCR, increased (P < 0.05) after ST. Conversely, the single RE bout decreased myostatin mRNA after ST, with the decrease showing a negative correlation (r = -0.65, P < 0.05) with the long-term increase in myostatin during ST. Furthermore, RE before ST increased myogenin mRNA (P < 0.05) and tended to increase after ST (P = 0.08). Myostatin receptor activin IIb mRNA levels were decreased at 1 h after RE in the pre-ST condition (P = 0.05) and also tended to decrease in the post-ST condition (P = 0.07). RE-induced downregulation in myostatin mRNA correlated with the ST induced increase in total body muscle mass (r = -0.82, P = 0.002). CONCLUSIONS: A single bout of RE in older men can downregulate the expression of myostatin receptor activin IIb mRNA. ST influences the response of myostatin to RE, as short-term RE-induced downregulation of myostatin was observed only after ST. The results also indicate that RE-induced alterations in myostatin mRNA expression may have a role in ST-induced muscle hypertrophy. PMID- 17277594 TI - Effects of whey isolate, creatine, and resistance training on muscle hypertrophy. AB - PURPOSE: Studies that have attributed gains in lean body mass to dietary supplementation during resistance exercise (RE) training have not reported these changes alongside adaptations at the cellular and subcellular levels. Therefore, the purpose of this study was to examine the effects of two popular supplements- whey protein (WP) and creatine monohydrate (CrM) (both separately and in combination)--on body composition, muscle strength, fiber-specific hypertrophy (i.e., type I, IIa, IIx), and contractile protein accrual during RE training. METHODS: In a double-blind randomized protocol, resistance-trained males were matched for strength and placed into one of four groups: creatine/carbohydrate (CrCHO), creatine/whey protein (CrWP), WP only, or carbohydrate only (CHO) (1.5 g x kg(-1) body weight per day). All assessments were completed the week before and after an 11-wk structured, supervised RE program. Assessments included strength (1RM, three exercises), body composition (DEXA), and vastus lateralis muscle biopsies for determination of muscle fiber type (I, IIa, IIx), cross-sectional area (CSA), contractile protein, and creatine (Cr) content. RESULTS: Supplementation with CrCHO, WP, and CrWP resulted in significantly greater (P < 0.05) 1RM strength improvements (three of three assessments) and muscle hypertrophy compared with CHO. Up to 76% of the strength improvements in the squat could be attributed to hypertrophy of muscle involved in this exercise. However, the hypertrophy responses within these groups varied at the three levels assessed (i.e., changes in lean mass, fiber-specific hypertrophy, and contractile protein content). CONCLUSIONS: Although WP and/or CrM seem to promote greater strength gains and muscle morphology during RE training, the hypertrophy responses within the groups varied. These differences in skeletal muscle morphology may have important implications for various populations and, therefore, warrant further investigation. PMID- 17277596 TI - Endurance running performance after 48 h of restricted fluid and/or energy intake. AB - PURPOSE: To determine the effect of a 48-h period of either fluid restriction (FR), energy restriction (ER), or fluid and energy restriction (F + ER) on 30-min treadmill time trial (TT) performance in temperate conditions. METHODS: Thirteen males participated in four randomized 48-h trials (mean +/- SD: age, 21 +/- 3 yr; VO2max 50.9 +/- 4.3 mL x kg(-1) x min(-1)). Control (CON) participants received their estimated energy (2903 +/- 199 kcal x d(-1)) and water (3912 +/- 500 mL x d(-1)) requirements. For FR, participants received their energy requirements and 193 +/- 50 mL x d(-1) water to drink, and for ER, participants received their water requirements and 290 +/- 20 kcal x d(-1). F + ER was a combination of FR and ER. After 48 h, participants performed a 30-min treadmill TT in temperate conditions (19.7 +/- 0.6 degrees C). A separate investigation (N = 10) showed the TT to be highly reproducible (CV 1.6%). RESULTS: Body mass loss (BML) was 0.6 +/- 0.4% (CON), 3.2 +/- 0.5% (FR), 3.4 +/- 0.3% (ER), and 3.6 +/- 0.3% (F + ER). Compared with CON (6295 +/- 513 m), less distance was completed on ER (10.3%) and F + ER (15.0%: P < 0.01). Although less distance was completed on FR (2.8%), this was not significantly different from CON. CONCLUSIONS: These results show a detrimental effect of a 48-h period of ER but no significant effect of FR on 30 min treadmill TT performance in temperate conditions. Therefore, these results do not support the popular contention that modest hypohydration (2-3% BML) significantly impairs endurance performance in temperate conditions. PMID- 17277595 TI - Effects of resistance exercise on lipolysis during subsequent submaximal exercise. AB - PURPOSE: This study examined effects of prior resistance exercise on fat metabolism during subsequent submaximal exercise with different recovery periods between exercise bouts. METHODS: Ten male subjects performed three types of exercise regimens: 1) submaximal endurance exercise only (E), 2) submaximal endurance exercise with prior resistance exercise and 20 min of rest (RE20), and 3) submaximal endurance exercise with prior resistance exercise and 120 min of rest (RE120). Resistance exercise consisted of six exercises, each with three to four sets at 10-repetition maximum. Subjects performed cycle ergometer exercise at 50% of the maximal oxygen uptake for 60 min. RESULTS: Prior resistance exercise caused increases in blood lactate, plasma norepinephrine, serum growth hormone (GH), insulin, and glycerol concentrations (P < 0.01). Before the submaximal exercise, serum free fatty acid (FFA) concentration was higher in the RE120 than in the RE20 and E trials (P < 0.01), although concentrations of plasma norepinephrine, serum GH, insulin, and glycerol were higher in the RE20 than in the RE120 and E trials (P < 0.05). Concentrations of FFA and glycerol during the 60-min submaximal exercise were higher in the RE120 and RE20 trials than in the E trial (P < 0.05). No significant difference was observed in the acetoacetate and 3-hydroxybutyrate responses. In the RE20 trial, fat oxidation throughout the 60 min submaximal exercise (mean value) was greater than in the E trial (P < 0.05), but no significant difference was found between the RE120 and E trials. CONCLUSION: Fat availability during the submaximal exercise was enhanced by prior resistance exercise. However, augmentation of fat oxidation was observed only in the trial with shorter rest between resistance exercise and submaximal exercise bouts (RE20 trial). PMID- 17277597 TI - Influence of hydration status on thermoregulation and cycling hill climbing. AB - PURPOSE: Although dehydration can impair endurance performance, a reduced body mass may benefit uphill cycling by increasing the power-to-mass ratio. This study examined the effects of a reduction in body mass attributable to unreplaced sweat losses on simulated cycling hill-climbing performance in the heat. METHODS: Eight well-trained male cyclists (mean +/- SD: 28.4 +/- 5.7 yr; 71.0 +/- 5.9 kg; 176.7 +/- 4.7 cm; VO2peak: 66.2 +/- 5.8 mL x kg(-1) x min(-1)) completed a maximal graded cycling test on a stationary ergometer to determine maximal aerobic power (MAP). In a randomized crossover design, cyclists performed a 2-h ride at 53% MAP on a stationary ergometer, immediately followed by a cycling hill-climb time-to exhaustion trial (88% MAP) on their own bicycle on an inclined treadmill (8%) at approximately 30 degrees C. During the 2-h ride, they consumed either 2.4 L of a 7% carbohydrate (CHO) drink (HIGH) or 0.4 L of water (LOW) with sport gels to match for CHO content. RESULTS: After the 2-h ride and before the hill climb, drinking strategies influenced body mass (LOW -2.5 +/- 0.5% vs HIGH 0.3 +/- 0.4%; P < 0.001), HR (LOW 158 +/- 15 vs HIGH 146 +/- 15 bpm; P = 0.03), and rectal temperature (T(re): LOW 38.9 +/- 0.2 vs HIGH 38.3 +/- 0.2 degrees C; P = 0.001). Despite being approximately 1.9 kg lighter, time to exhaustion was significantly reduced by 28.6 +/- 13.8% in the LOW treatment (LOW 13.9 +/- 5.5 vs HIGH 19.5 +/- 6.0 min, P = 0.002), as was the power output for a fixed speed (LOW 308 +/- 28 vs HIGH 313 +/- 28 W, P = 0.003). At exhaustion, T(re) was higher in the LOW treatment (39.5 vs HIGH 39.1 degrees C; P < 0.001), yet peak HR, blood lactate, and glucose were similar. CONCLUSION: Exercise-induced dehydration in a warm environment is detrimental to laboratory cycling hill-climbing performance despite reducing the power output required for a given speed. PMID- 17277598 TI - Gait-related risk factors for exercise-related lower-leg pain during shod running. AB - PURPOSE: Exercise-related lower-leg pain (ERLLP) is a common chronic sports injury. In clinical practice, deviant gait biomechanics are frequently considered to play a role in the development of ERLLP, although there is scarce scientific evidence that gait-related variables predispose athletes to this injury. The purpose of this study was to examine prospectively the gait-related risk factors for ERLLP during shod running in a young, physically active population. METHODS: The gait pattern during shod running of 400 physical education students was evaluated at the beginning of their academic study. This was accomplished by means of plantar pressure measurements and 3D gait kinematics. After this evaluation, the same sports physician registered all sports injuries during this study. RESULTS: During the follow-up period, 46 subjects developed ERLLP, of whom 29 subjects had bilateral complaints. Thus, 75 symptomatic lower legs (35 left and 40 right) were classified into the ERLLP group. Bilateral feet of 167 subjects who sustained no injuries at the lower extremities served as the referent group. Cox regression analysis revealed that subjects who will develop ERLLP have an altered running pattern compared with the referent subjects. More specifically, these subjects showed a significantly increased pronation excursion, accompanied by more pressure underneath the medial side of the foot, a delayed maximal eversion, and an accelerated reinversion. CONCLUSION: The findings of this study suggest that altered gait biomechanics during shod running play a role in the genesis of ERLLP and, thus, should be considered in prevention and rehabilitation of this pathology. PMID- 17277599 TI - Optimal loading for maximal power output during lower-body resistance exercises. AB - PURPOSE: The influence of various loads on power output in the jump squat (JS), squat (S), and power clean (PC) was examined to determine the load that maximizes power output in each lift. METHODS: Twelve Division I male athletes participated in four testing sessions. The first session involved performing one-repetition maximums (1RM) in the S and PC, followed by three randomized testing sessions involving either the JS, S, or PC. Peak force, velocity, and power were calculated across loads of 0, 12, 27, 42, 56, 71, and 85% of each subject's 1RM in the JS and S and at 10% intervals from 30 to 90% of each subject's 1RM in the PC. RESULTS: The optimal load for the JS was 0% of 1RM; absolute peak power was significantly lower from the optimal load at 42, 56, 71, and 85% of 1RM (P < or = 0.05), whereas peak power relative to body mass was significantly lower at 27% of 1RM in addition to 42, 56, 71, and 85% of 1RM. Peak power in the S was maximized at 56% of 1RM; however, power was not significantly different across the loading spectrum. The optimal load in the PC occurred at 80% of 1RM. Relative peak power at 80% of 1RM was significantly different from the 30 and 40% of 1RM. CONCLUSION: This investigation indicates that the optimal load for maximal power output occurs at various percentages of 1RM in the JS, S, and PC. PMID- 17277600 TI - Relationship between %HRmax, %HR reserve, %VO2max, and %VO2 reserve in elite cyclists. AB - PURPOSE: To evaluate the relations between %HRmax, %HRR, %VO2max, and %VO2R in elite cyclists and to check whether the intensity scale recommended by ACSM in its 1998 position stand is also applicable to this specific population. METHODS: Twenty-six male elite road cyclists (25.1 +/- 0.7 yr, 71.0 +/- 1.2 kg, 70.9 +/- 1.2 mL x kg(-1) x min(-1), 433.9 +/- 9.8 W) performed an incremental maximal exercise test (50 W x 3 min(-1)). Individual linear regressions based on HR and VO2 values measured at rest, end of each stage, and maximum, were used to calculate slopes and intercepts, and to predict %HRmax, %HRR, %VO2max, or %VO2R for a given exercise intensity. RESULTS: Below 85% VO2max or VO2R, predicted %HRmax values were significantly higher (P < 0.001) than the ACSM intensity scale (58, 65, 73, and 87% vs 55, 62, 70, and 85% HRmax at 40, 50, 60, and 80% VO2max, and 48, 61, 74% vs 35, 55, and 70% HRmax at 20, 40, and 60% VO2R). The %HRR versus %VO2max regression mean slope (1.069 +/- 0.01) and intercept (-5.747 +/- 0.80) were significantly different (P < 0.0001) from 1 and 0, respectively. Conversely, the %HRR versus %VO2R regression was indistinguishable from the line of identity (mean slope = 1.003 +/- 0.01; mean intercept = 0.756 +/- 0.7). Predicted %VO2R values were equivalent to %HRR in the 35-95%HRR range. %VO2max was equivalent to %HRR at and above 75%HRR, and it was significantly higher at (P < 0.05) and below 65%HRR (P < 0.001). CONCLUSION: The intensity scale recommended by ACSM underestimates exercise intensity in elite cyclists. Prediction of %HRR by %VO2R is better than by %VO2max. Thus, elite cyclists should use %HRR in relation to %VO2R rather than in relation to %VO2max. PMID- 17277601 TI - Force-velocity and power-velocity relationships during maximal short-term rowing ergometry. AB - INTRODUCTION: Maximal rowing power-velocity relationships that exhibit ascending and descending limbs and a local maximum have not been reported. Further, duty cycle (portion of the stroke occupied by the pull phase) is unconstrained during rowing and is known to influence average muscular power output. PURPOSE: Our purposes for conducting this study were to fully describe maximal short-term rowing force-velocity and power-velocity relationships. Within the context of those purposes, we also aimed to determine the apex of the power-velocity relationship and the influence of freely chosen duty cycle on stroke power. METHODS: Collegiate varsity male rowers (N = 11, 22.9 +/- 2.3 yr, 84.1 + 12.1 kg, 184 +/- 7 cm) performed five maximal rowing trials using an inertial load ergometer. For each stroke, we determined force and power averaged for the pull phase and the complete stroke, instantaneous peak force and power, average handle velocity for the pull phase, handle velocity at peak instantaneous force and power, pull time, recovery time, and freely chosen duty cycle. Force-velocity and power-velocity relationships were characterized using regression analyses, and optimal velocities were determined from the regression coefficients. RESULTS: Pull force-velocity (r2 = 0.99) and peak instantaneous force-velocity (r2 = 0.93) relationships were linear. Stroke power (r2 = 0.98), pull power (r2 = 0.99), and instantaneous peak power (r2 = 0.99) were quadratic, with apexes at 2.04, 3.25, and 3.43 m x s(-1), respectively. Maximum power values were 812 +/- 28 W (9.8 +/- 0.4 W x kg(-1)), 1995 +/- 67 W (23.9 +/- 0.7 W x kg(-1)), and 3481 +/- 112 W (41.9 +/- 1.3 W x kg(-1)) for stroke, pull, and instantaneous power, respectively. Freely chosen duty cycle decreased from 58 +/- 1% on the first stroke to 26 +/- 1% on the fifth stroke. CONCLUSIONS: These data characterized the maximal rowing force-velocity and power-velocity relationships and identified the optimal velocity for producing maximal rowing power. Differences in maximum pull and stroke power emphasized the importance of duty cycle. PMID- 17277602 TI - Postexercise heart rate recovery accelerates in strength-trained athletes. AB - The left ventricle morphologically adapts to endurance exercise training (eccentric cardiac remodeling) and strength exercise training (concentric remodeling). In addition, the acceleration of vagally mediated heart rate (HR) recovery after exercise is one of the functional adaptations of the heart in endurance-trained humans. However, the effect of strength training on HR recovery is unclear. PURPOSE: The purpose of this study was to investigate whether postexercise HR recovery accelerates in strength-trained athletes. METHODS: Subjects were young strength-trained athletes (ST; N = 12), endurance-trained athletes (ET; N = 12), and age-matched sedentary control men (C; N = 12). HR and oxygen uptake were measured during submaximal exercise (cycling exercise, 40% maximal oxygen uptake for 8 min) and 30 s after the exercise (the postexercise period). RESULTS: Left ventricular end-diastolic dimension was higher in both types of athletes compared with C, but greater in ET than in ST (C, 4.3 +/- 0.1 cm; ET, 5.0 +/- 0.1 cm; ST, 4.8 +/- 0.1 cm). Left ventricular average wall thickness was greater in ST in comparison with ET, although it was higher in both trained men compared with C (C, 0.85 +/- 0.02 cm; ET, 0.90 +/- 0.02 cm; ST, 1.00 +/- 0.02 cm). The time constant of postexercise HR decay, an index of vagally mediated postexercise HR recovery, was lower in ST and ET compared with C (C, 94.4 +/- 9.2 s; ET, 65.9 +/- 4.3 s; ST, 69.1 +/- 4.0 s). Oxygen pulse was greater in ST and ET than in C (C, 9.4 +/- 0.6 mL per beat; ET, 13.0 +/- 0.9 mL per beat; ST, 12.8 +/- 0.4 mL per beat), and it results in increased oxygen debt for both types of athletes (C, 0.257 +/- 0.024 L; ET, 0.343 +/- 0.030 L; ST, 0.331 +/- 0.017 L). We did not find significant differences in these indices between ST and ET. CONCLUSIONS: These results suggest that the HR recovery immediately after exercise is accelerated in both strength- and endurance-trained athletes. PMID- 17277603 TI - School-based physical activity does not compromise children's academic performance. AB - PURPOSE: The purpose of this study was twofold: 1) to evaluate the effectiveness of a school-based physical activity intervention, Action Schools! BC (AS! BC), for maintaining academic performance in a multiethnic group of elementary children, and 2) to determine whether boys and girls' academic performance changed similarly after participation in AS! BC. METHODS: This was a 16-month cluster randomized controlled trial. Ten schools were randomized to intervention (INT) or usual practice (UP). One INT school administered the wrong final test, and one UP school graded their own test, so both were excluded. Thus, eight schools (six INT, two UP) were included in the final analysis. Children (143 boys, 144 girls) in grades 4 and 5 were recruited for the study. We used the Canadian Achievement Test (CAT-3) to evaluate academic performance (TotScore). Weekly teacher activity logs determined amounts of physical activity delivered by teachers to students. Physical activity was determined with the Physical Activity Questionnaire for Children (PAQ-C). Independent t-tests compared descriptive variables between groups and between boys and girls. We used a mixed linear model to evaluate differences in TotScore at follow-up between groups and between girls and boys. RESULTS: Physical activity delivered by teachers to children in INT schools was increased by 47 min x wk(-1) (139 +/- 62 vs 92 +/- 45, P < 0.001). Participants attending UP schools had significantly higher baseline TotScores than those attending INT schools. Despite this, there was no significant difference in TotScore between groups at follow-up and between boys and girls at baseline and follow-up. CONCLUSION: The AS! BC model is an attractive and feasible intervention to increase physical activity for students while maintaining levels of academic performance. PMID- 17277604 TI - American College of Sports Medicine position stand. Exercise and fluid replacement. AB - This Position Stand provides guidance on fluid replacement to sustain appropriate hydration of individuals performing physical activity. The goal of prehydrating is to start the activity euhydrated and with normal plasma electrolyte levels. Prehydrating with beverages, in addition to normal meals and fluid intake, should be initiated when needed at least several hours before the activity to enable fluid absorption and allow urine output to return to normal levels. The goal of drinking during exercise is to prevent excessive (>2% body weight loss from water deficit) dehydration and excessive changes in electrolyte balance to avert compromised performance. Because there is considerable variability in sweating rates and sweat electrolyte content between individuals, customized fluid replacement programs are recommended. Individual sweat rates can be estimated by measuring body weight before and after exercise. During exercise, consuming beverages containing electrolytes and carbohydrates can provide benefits over water alone under certain circumstances. After exercise, the goal is to replace any fluid electrolyte deficit. The speed with which rehydration is needed and the magnitude of fluid electrolyte deficits will determine if an aggressive replacement program is merited. PMID- 17277605 TI - The 6-min walk test: a useful test in elderly patients with heart failure? PMID- 17277607 TI - Accuracy of radiopill telemetry during distance running in the heat. PMID- 17277609 TI - Molecular epidemiology of genital chlamydial infection among male patients attending an STD clinic in Taipei, Taiwan. AB - OBJECTIVE: To assess the epidemiology of genital Chlamydia trachomatis infection among men attending an STD clinic in Taipei, Taiwan. STUDY: Between July 2004 and June 2005, a total of 426 first-void urine specimens from male patients were tested for C. trachomatis by using a urine-based PCR DNA amplification assay. RESULTS: The overall prevalence of genital C. trachomatis infection was 16.4%. Youth, current symptoms, the presence of N. gonorrhoeae infection, and inconsistent use of condoms were positively associated with C. trachomatis infection. The most common chlamydia strain present was genotype E, followed by D and Da, F, K, J, G, and H. CONCLUSIONS: C. trachomatis genital infection was prevalent among male patients attending a STD clinic in Taipei. Young Taiwanese men attending STD clinics should be counselled on condom use. PMID- 17277610 TI - Clustering of syringe sharing and unprotected sex risk behaviors in male injecting drug users in China. AB - OBJECTIVES: To investigate, among male injecting drug users (IDU), the relationships between higher risk IDU-related and sex-related behaviors. GOAL: To highlight the clustering effects of the 2 forms of risk behaviors. STUDY DESIGN: Behavioral surveillance surveys conducted in Sichuan were analyzed (n = 3105). RESULTS: Of all respondents, 35.7% had injected with others' used syringes in the last 6 months, which was associated with female sex workers (FSW) and nonregular sex partners (NRP) partnership (OR = 1.81 and 1.59 respectively), and having had unprotected sex with FSW, NRP, and regular sex partners (OR = 1.96, 1.57, and 1.38 respectively). Higher drug use frequency was associated with having unprotected sex with FSW (among client of FSW, OR = 1.7) and with NRP (among those with NRP, OR = 1.61). Giving used syringes to others for injection was also associated with unprotected sex with NRP (OR = 1.97). CONCLUSIONS: Interventions are urgently required to reduce both IDU-related and sex-related risk behaviors among male IDU. PMID- 17277611 TI - Trends in the use of sexually transmitted disease diagnostic technologies in California, 1996-2003. AB - OBJECTIVE: To describe trends in STD diagnostic test volume and test technology in California from 1996 to 2003. STUDY: A self-administered survey was mailed annually to licensed clinical laboratories in California that performed STD testing. Data were collected on volume and diagnostic test type for chlamydia, gonorrhea, syphilis, chancroid, HIV, hepatitis B, herpes simplex virus (HSV), and human papilloma virus (HPV). Data were analyzed for trends over time. RESULTS: Response rates ranged from 77% to 99% per survey year. The total number of chlamydia, gonorrhea, and syphilis tests increased from 8.1 to 9.3 million annually. The proportion of chlamydia and gonorrhea tests performed using nucleic acid amplification testing increased from 5% to 66% and from 1% to 59%, respectively. Gonorrhea culture testing decreased from 42% to 10% of all gonorrhea tests. HIV test volume increased from 2.4 to 3.1 million tests. Newer technology tests for HSV and HPV were less common but increased in use. Non public health laboratories conducted over 90% of all STD testing. CONCLUSIONS: Analyzing trends in diagnostic technologies enhances our understanding of the epidemiology of STDs and monitoring laboratory capacity and practices facilitates implementation of STD control activities. PMID- 17277613 TI - Role of nitric oxide in the development of distant metastasis from squamous cell carcinoma. AB - BACKGROUND: Metastasis, the dissemination of malignant cells to distant sites, remains one of the most significant factors responsible for death from cancer. Recent studies have shown some improvement in the rate of distant metastasis (DM) with the addition of chemotherapy to surgery and radiation for treatment of head and neck squamous cell carcinoma (HNSCC). However, diagnosis and treatment at an early stage ultimately leads to a better prognosis. The prediction of which patients will develop metastasis and the selection of treatment most effective at preventing and treating metastasis remains dependent on an incomplete understanding of prognostic factors and the biological and molecular basis for metastatic development. This study was undertaken using an in vivo model to investigate the possible role of nitric oxide (NO) in the development of metastasis from HNSCC. The findings will result in better understanding of the metastatic process for HNSCC, with the potential to develop and implement therapies that could prevent and treat metastasis in patients. OBJECTIVES/HYPOTHESIS: 1) To analyze whether in vivo videomicroscopy (IVVM) is useful for the study of DM from squamous cell carcinoma of the head and neck; 2) with use of IVVM, investigate the effect of the biological mediators NO and interleukin (IL)-1 on the adhesion of circulating human HNSCC cells in the hepatic microcirculation. STUDY DESIGN: Prospective study using an animal model. METHODS: Phase 1: athymic nude rats and mice were used for IVVM experiments. The cremaster muscle and liver, used as arterial and venous flow models, were tested to determine whether IVVM was useful for the study of human HNSCC interactions with the microcirculation. A human squamous cell carcinoma cell line (FaDu) labeled with the intracytoplasmic fluorescent marker BCECF-am. was used for all experiments. Videomicroscopic images of FaDu cells in the microcirculation were analyzed for cell adhesion, morphology, deformation, circulation, location of adhesion within the microcirculation, and alteration of microvascular circulation. Phase 2: the effect of IL-1, NO, and NO inhibitors on HNSCC cell adhesion in the hepatic microcirculation of nude mice was analyzed by IVVM. This was followed by histologic determination of the ratio of FaDu cells present for liver area analyzed. Nude mice were treated with 1) IL-1; 2) L-arginine (an NO substrate); or 3) L-N-monomethyl-L-arginine (an NO synthase inhibitor) alone or in combination. These data were analyzed statistically to determine the effect on cell adhesion in the liver. RESULTS: IVVM provided a method for the study of circulating HNSCC with the microcirculation in both the cremaster and liver models. FaDu cells were arrested at the inflow side of the circulation, with maintenance of cell integrity. L-arginine and IL-1 both increased FaDu cell arrest in the liver above baseline (P = .00008 and P = .03), and the combination of these agents potentiated the effect (P = .000009). CONCLUSIONS: IVVM allows direct assessment of circulating HNSCC with the microcirculation and is a powerful model for the study of DM. NO and IL-1 play a role in increasing the arrest of HNSCC in the liver and are important in the generation of DM in patients with HNSCC. PMID- 17277614 TI - 5-Fluorouracil ointment for the treatment of otitis media with effusion. AB - OBJECTIVES/HYPOTHESIS: Our aim was to evaluate the combined effect of 5 fluorouracil (5-FU) and myringotomy for the treatment of otitis media with effusion (OME). OME is usually treated with medication, myringotomy, or insertion of a ventilation tube (VT). Except for VT insertion, however, treatment effects are short-lived. VT insertion has numerous sequelae: increased susceptibility to infection, large perforation of the tympanic membrane, cholesteatoma, and eventual hearing deterioration. We estimated the depressant action of 5-FU on normal cell proliferation in vitro. In addition, clinically, we assessed whether 5-FU has the potential to prolong the effect of myringotomy. STUDY DESIGN: An in vitro study and a clinical study were conducted. MATERIALS AND METHODS: In study I, fibroblasts harvested from the peritoneum of three green fluorescent protein transgenic mice were cultured with different doses of 5-FU. After 2 weeks, their proliferation rates were compared. In study II, patients (54 males, 47 females) were selected randomly from a group of patients with intractable OME. Myringotomy with or without a single dose of 5-FU ointment (approximately 0.10-0.30 mg) was performed in group I (n = 64) and group II (n = 37), respectively. The natural closure rates of the tympanic membrane were assessed in both groups. RESULTS: In vitro, 5-FU inhibited the growth of fibroblasts in a dose-dependent manner. The average time to tympanic membrane closure was 20.5 days in group I and 8.1 days in group II. No adverse events were observed in either group. CONCLUSIONS: Topical application of 5-FU ointment is useful in prolonging the effect of myringotomy. 5-FU ointment therapy is easy, safe, and cost-effective and may be of wide application. PMID- 17277615 TI - Laser eustachian tuboplasty: two-year results. AB - OBJECTIVE/HYPOTHESIS: Laser eustachian tuboplasty (LETP) combined with appropriate medical management will eliminate the chronic presence of middle ear effusions in selected patients. METHODS: The study population consisted of 13 adults with otitis media with effusion (OME). Patients underwent slow-motion video endoscopy to identify the location and extent of surgical resection. A diode or argon laser was used to vaporize areas of hypertrophic mucosa and submucosa along the cartilaginous eustachian tube. Patients were evaluated at 6, 12, and 24 months. Successful outcome was defined as absence of OME. Patients with evidence of reflux disease or allergic rhinitis were treated with medical therapy before surgery and throughout the follow-up period as indicated. RESULTS: LETP combined with medical management eliminated OME in 36% (4 of 11) of patients at 6 months, 40% (4 of 10) at 1 year, and 38% (3 of 8) at 2 years. Failure of LETP correlated with presence of laryngopharyngeal reflux (P = .01) or allergic disease (P = .05) for the results at 1 year but not at 2 years. CONCLUSIONS: LETP combined with appropriate medical management may be an effective treatment in select patients with chronic persistent eustachian tube dysfunction. A controlled trial with a larger number of subjects will be necessary to determine the efficacy of LETP and identify those factors predictive of successful outcome. PMID- 17277616 TI - Distress in spouses and patients after treatment for head and neck cancer. AB - BACKGROUND: The objective of this study is to obtain insight into distress in spouses and patients treated for head and neck cancer. METHODS: Forty-one patient spouse pairs completed the Hospital Anxiety and Depression Scale (HADS). Inclusion criteria included curative treatment for head and neck cancer. Exclusion criteria were visiting the clinic without a spouse, bad news at the routine follow-up examination, diseases causing cognitive dysfunction, and poor understanding of the Dutch language. Next to the HADS, the assessment protocol included age, gender, health status, coping strategy, time since cancer treatment, tumor stage and site, treatment modality, functional and social impairment, and caregiving burden. RESULTS: A clinical level of distress was noted in 20% of the spouses and in 27% of the patients. Distress in spouses was related to the presence of a feeding tube in patients, a passive coping style, less vitality, and a disrupted daily life schedule resulting from caregiving. Distress in patients was related to the presence of a feeding tube, speech and swallowing problems, less social contacts, a passive style of coping, and nonexpression of emotions. CONCLUSION: Distress is often present in spouses and patients treated for head and neck cancer. Routine screening for psychologic distress is recommended. PMID- 17277617 TI - Efficacy of radiologic screening for distant metastases and second primaries in newly diagnosed patients with head and neck cancer. AB - OBJECTIVES: Detection of distant metastases and second primary tumors in newly diagnosed patients with head and neck cancer has usually a major effect on prognosis but does not always influence clinical management. This must be considered when radiologic screening investigations are used. The present study particularly evaluates how often additional neoplastic lesions detected by screening had an impact on therapy. STUDY DESIGN: The authors conducted a single institution retrospective analysis. METHODS: The medical records of 260 patients with newly diagnosed squamous cell carcinoma of the head and neck treated between 1999 and 2002 were retrospectively analyzed. Before therapy, all patients had undergone screening by computed tomography scan of the chest, abdominal ultrasound, and bone scintigraphy. RESULTS: Screening investigations identified 16 patients (6.2%) with distant metastases and six patients (2.3%) with simultaneous second primaries. Chest computed tomography scan detected 20 neoplastic lesions; abdominal ultrasound and bone scintigraphy each detected 2. Three findings of distant metastases proved to be false-positive during follow up. Of the 22 patients with positive screening results, clinical management was affected in 13 (59.1%). Twelve were originally scheduled for curative surgery and 10 had chest abnormalities. CONCLUSION: Chest computed tomography scan was the most effective screening investigation, which should be routinely used whenever curative surgery of head and neck cancer is planned. Abdominal ultrasound and bone scintigraphy may sometimes be valuable before extensive surgical treatment of far advanced disease. In patients scheduled for primary radiotherapy, radiologic screening had hardly any consequence and should be confined to conventional x-ray of the chest. PMID- 17277618 TI - Protein expression of the tumor suppressors p16INK4A and p53 and disease progression in recurrent respiratory papillomatosis. AB - BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a benign condition that rarely metastasizes as invasive squamous cell carcinoma. Although this disease is associated with human papillomavirus, the role of this virus in tumorigenesis is unclear. OBJECTIVES: The aim of this study is to assess the involvement of the tumor suppressors P16INK4A and p53 in RRP tumor progression. DESIGN: Immunohistochemistry of p16INK4A and p53 was performed on biopsies of recurrent squamous papillomas and invasive lesions in nine patients. RESULTS: Twenty biopsies were graded as papillomas (RP), three as papillomas with high-grade dysplasia/carcinoma in situ (HGD/CIS), and two as invasive squamous cell carcinoma (SCCA). Forty-five percent of RP and 60% of HGD/CIS/SCCA expressed p16INK4A. Fifty percent of RP and 100% of HGD/CIS/SCCA expressed p53. The difference in the frequency of p53-positive staining between HGD/CIS and SCCA (100% of tissues examined) and RP (50% of tissues examined) approached statistical significance. Neither p16INK4A nor p53 was predictive of invasive transformation. CONCLUSIONS: Expression of p16INK4A, which is a surrogate for the tumor suppressor retinoblastoma (Rb), did not immediately lead to invasive disease. There is no correlation between disease severity of RRP and level of p16INK4A. PMID- 17277619 TI - Complications of chronic suppurative otitis media and their management. AB - OBJECTIVE: The objective of this is to determine the incidence of otogenic complications of chronic suppurative otitis media (CSOM) and its management. STUDY DESIGN: The authors conducted a retrospective study. METHODS: The study was conducted at the tertiary referral and teaching hospital. An analysis was made about the clinical and operative findings, surgical techniques and approaches, the overall management and recovery of the patients. The data were then compared with the relevant and available literature. RESULTS: Of the 70 cases, 47 (67%) had a single complication, of which eight (11%) had intracranial and 39 (56%) had extracranial complications. Twenty-three (33%) had two or more complications. The commonly encountered intracranial complications were otitic meningitis, lateral sinus thrombosis, and cerebellar abscess, which were seen in 13 (19%), 10 (14%), and 6 (9%) cases, respectively. Among the extracranial complications, mastoid abscess, postauricular fistula, and facial palsy were encountered in 26 (37%), 17 (24%) and 10 (14%) patients, respectively. Surgeries were the main mode of treatment for these conditions. According to severity, we found four different types of the lateral sinus involvement. Three patients with otitic facial palsy failed to regain full facial function despite surgery. A total of nine patients with the diagnosis of otitic meningitis, lateral sinus thrombosis and interhemispheric abscess expired. It constituted the mortality rate of 13% in our study. CONCLUSION: CSOM complications, despite its reduced incidence, still pose a great challenge in developing countries as the disease present in the advanced stage leading to difficulty in management and consequently higher morbidity and mortality. PMID- 17277620 TI - Effect of surgical treatment on lymphoproliferation in advanced supraglottic laryngeal cancer. AB - OBJECTIVES: The capacity of cell immunity to act against tumor cells has been presented as a decisive influence in the prognosis of patients with cancer. The aim of this study was to evaluate lymphoproliferation in nonadherent peripheral blood cell cultures of patients with advanced supraglottic laryngeal cancer. STUDY DESIGN: Fourteen patients with advanced supraglottic laryngeal cancer were studied prospectively. Lymphoproliferation was quantified by adding 3H-thymidine and measured in counts/minute using liquid scintillation spectrometry. Based on the ratio between stimulated and baseline cultures, the proliferation index was calculated before and 236 +/- 18 days after the surgery. RESULTS: Lymphoproliferation was lower in patients than in healthy controls (P = .01) in the preoperative as well as in the late postoperative period (P = .006 and P = .02, respectively). However, there was no change from preoperative to late postoperative. CONCLUSION: Pre- and postoperative results show that patients with advanced supraglottic laryngeal cancer present lymphoproliferation diminished before the surgery, and in the late postoperative period, there was no recovery of immune capacity evaluated by lymphoproliferation measurement. PMID- 17277621 TI - Identification of viruses in patients with postviral olfactory dysfunction. AB - OBJECTIVE: Causative viruses of postviral olfactory dysfunction (PVOD) have not yet been identified. The aim of this study was to investigate causative viruses in patients with PVOD. STUDY DESIGN AND METHODS: Nasal discharge was collected from 24 patients with PVOD. We investigated the presence of 10 viruses in nasal discharge and examined the time course, with regard to changes in olfactory dysfunction and nasal obstruction in patients with PVOD, using questionnaires, acoustic rhinometry, and olfactory tests. RESULTS: Rhinoviruses were detected in 10 patients by electrophoresis. Rhinoviruses were also confirmed in four patients by nucleotide sequences. Viral serotypes were identified to be human rhinovirus (HRV)-40, HRV-75, HRV-78, and HRV-80. One of the four patients complained of anosmia, whereas another complained of dysosmia. Olfactory testing did not show significant improvement at 4, 8, 11, and 24 weeks after the first visit in the four patients, although results of acoustic rhinometry significantly improved. Two of the four patients complained of olfactory dysfunction even 6 months after the first visit. Coronavirus and parainfluenza virus were detected in one patient each, and Epstein-Barr viruses were detected in three patients. CONCLUSIONS: This study for the first time detected rhinovirus, coronavirus, parainfluenza virus, and Epstein-Barr virus in nasal discharge of patients with PVOD. Furthermore, the present study suggests that rhinoviruses can cause olfactory dysfunction through mechanisms other than nasal obstruction and that rhinoviruses can induce various severities and different time courses of olfactory dysfunction. PMID- 17277622 TI - Extracranial head and neck schwannomas: a clinical analysis of 33 patients. AB - OBJECTIVE: To study the clinical features, diagnosis, and management of the extracranial head and neck schwannomas. STUDY DESIGN: Retrospective study. METHODS: The clinical data of 33 patients with schwannoma of the head and neck from 1996 to 2006 were studied retrospectively. RESULTS: Extracranial head and neck schwannomas usually presented as solitary and well-demarcated lesions with insidious course. Although benign, the lesion can cause secondary symptoms, such as nasal obstruction, dysphasia, and hoarseness, relevant to location of the lesion. Fine needle aspiration cytology, computed tomography scans, and magnetic resonance imaging may provide limited implications in the diagnosis of schwannomas, whereas postoperative pathologic examination establishes the final diagnosis. CONCLUSIONS: Complete surgical excisions with appropriate approaches have proven to be efficient and successful in the treatment of head and neck schwannomas. PMID- 17277623 TI - Anatomic continuity of longitudinal pharyngeal and esophageal muscles. AB - OBJECTIVES: The pharyngeal and esophageal shortenings during deglutition are attributable to longitudinal muscle contraction. The two shortenings may be independent events because the longitudinal pharyngeal and esophageal muscular insertions are believed to be separated from each other. The aim of this study was to investigate the superior attachments of the longitudinal esophageal muscle. STUDY DESIGN: Prospective. METHODS: With use of dissection, sectional anatomy, and confocal microscopy, 30 adult cadavers were examined in this study. RESULTS: We found that the longitudinal esophageal muscle fibers had multiple superior insertions. Some of the fibers were continuous with the longitudinal pharyngeal muscles and merged with a membrane-like fascia that anchored the pharyngoesophageal wall to the thyroid cartilage. CONCLUSIONS: This study demonstrates that the longitudinal pharyngeal and esophageal muscle fibers are continuous with each other and are integrated with fibrous and cartilaginous structures. Such anatomic integrity at the pharyngoesophageal junction is important for the function of the upper esophageal sphincter. PMID- 17277624 TI - Surgical techniques and results of lateral thoracic cutaneous, myocutaneous, and conjoint flaps for head and neck reconstruction. AB - BACKGROUND: This paper aims at presentation of our surgical techniques and results of the lateral thoracic (LT) flaps for head and neck reconstructions. METHOD: There were seven LT cutaneous, seven LT myocutaneous, and two LT conjoint myocutaneous flaps for reconstruction of head and neck mucosal or cutaneous defects. RESULTS: The largest flap size was 22 cm x 13 cm. All donor sites were closed primarily. The highest point of reconstruction was in the nasopharynx internally and zygoma externally. All flaps survived without major complication. CONCLUSIONS: The LT flap has the versatility of cutaneous, myocutaneous, and conjoint flaps with pectoralis major or latissimus dorsi myocutaneous flaps to reconstruct large surgical defects. It has a large, reliable surface area, a long pedicle to reach nasopharynx and zygoma, and has less bulky muscle to facilitate tubular reconstruction of circumferential pharyngeal defect, one-stage operation, esthetic hidden donor site scar in axillary region, and minimal donor site morbidity. It is an additional reliable pedicle flap in our armamentarium for reconstruction of both cutaneous and mucosal defects in the head and neck region. PMID- 17277625 TI - Effects of halofuginone on fibrosis formation secondary to experimentally induced subglottic trauma. AB - OBJECTIVE: The aim of the study was to assess the antifibrotic effect of systemically applied halofuginone after subglottic injury. MATERIALS AND METHODS: After standardized trauma to subglottic area, rats were divided into two groups: a study group that received treatment and a control group that did not. The rats were treated with 0.1 mg/kg/day intraperitoneal halofuginone injection for 30 days. The larynx specimens were examined histopathologically under light microscope for epithelization, inflammation, necrosis, and fibrosis. RESULTS: The fibrosis indexes of the treated group were significantly less than those of the control group (P < .01). CONCLUSIONS: Systemically applied halofuginone hydrobromide decreases fibrosis/scar tissue formation secondary to experimentally induced acute subglottic trauma. PMID- 17277626 TI - Pulmonary recovery after rigid bronchoscopic retrieval of airway foreign body. AB - OBJECTIVE: The aim of this study was to determine how long postoperative pulmonary care is needed in patients after rigid bronchoscopic retrieval of foreign body from the airway and to identify the factors affecting pulmonary recovery. MATERIALS AND METHOD: A retrospective review of 98 pediatric patients who had foreign body removed from the airway by rigid bronchoscopic procedure was conducted. After the removal of the foreign body, the time required for complete clinical and radiologic pulmonary recovery was reviewed for each subject. Factors examined included age, sex, preoperative symptoms, preoperative radiologic findings, duration between the aspiration event and treatment, the type of foreign body, the location of foreign body impaction, operation time, immediate postoperative radiologic changes, and treatment outcome. RESULTS: More than 1 week for the complete pulmonary recovery was required in 25 (25.5%) cases, whereas 74.5% of subjects fully recovered within 1 week after the removal of foreign body. In the univariate analysis, preoperative inflammatory symptoms, and radiologic findings, an operation time of over 50 minutes and the aggravation of immediate postoperative radiologic findings predicted a delayed pulmonary recovery (more than 1 week). In the multivariate analysis, three of four variables previously noted, except preoperative inflammatory symptoms, showed significant predictability for a delayed pulmonary recovery. CONCLUSION: The recovery time of more than 1 week after rigid bronchoscopic retrieval of airway foreign body was associated with preoperative inflammatory findings by radiologic study, a prolonged procedure over 50 minutes, and aggravation of the immediate postoperative radiologic findings. Therefore, long-term pulmonary care is required for this group of patients. PMID- 17277627 TI - Blepharokymographic analysis of eyelid motion in Bell's palsy. AB - OBJECTIVE: To present characteristics of eyelid motion measured by blepharokymography in Bell's palsy patients and to discuss possible roles and limitations of blepharokymography. STUDY DESIGN: Retrospective analysis. METHODS: The study included 72 patients with Bell's palsy who presented to the Department of Otolaryngology at Asan Medical Center, Seoul, Korea, between April 2002 and March 2005, and who underwent both electroneuronography and blepharokymography. Parameters of eyelid motion were measured using revised blepharokymography. Correlations between blepharokymography and electroneuronography or House Brackmann grade were examined by Spearman rank correlation and Kendall's tau-b correlation, respectively. RESULTS: Compared with the normal side, all parameters of eyelid motion except opening time were decreased on the palsy side, with peak closing velocity showing the greatest difference (40.2%). On average, paralytic eyelids moved down 6.5 mm in 277 ms with a peak velocity of 55.4 mm/s, whereas normal eyelids moved down 9.7 mm in 214 ms, with a peak velocity of 142.6 mm/s. Subtle paralytic eyelid motion or "lid lag" could be objectively documented by blepharokymography to have longer and gentler downward slopes in displacement curves. Most blepharokymographic parameters correlated with ocular electroneuronography and House-Brackmann grade. CONCLUSIONS: Slow or incomplete closure of paralytic eyelids can be graphically and numerically analyzed by blepharokymography. Blepharokymography may be useful for evaluating status, predicting prognosis, and assessing effects of rehabilitative procedures, including gold weight implants in patients with facial palsy. PMID- 17277628 TI - Pediatric endoscopic dacryocystorhinostomy failures: who and why? AB - OBJECTIVE: The objectives of this study are to report outcomes of pediatric patients with nasolacrimal duct obstruction (NLDO) who underwent primary endoscopic dacryocystorhinostomy (DCR) and discuss causes of failure. STUDY DESIGN: The authors conducted a retrospective case series. METHODS: Charts of all patients less than 16 years of age who underwent primary endoscopic DCR from 1997 to 2004 were reviewed. Patients were grouped based on the presence or absence of facial anomalies or syndromes and whether the NLDO was congenital or acquired. Success was defined as complete resolution of symptoms, improvement included anatomic patency or partial symptoms, and failure as no improvement or demonstration of patency. RESULTS: Thirty-four patients (43 ducts) aged 11 months to 14 years were identified. There were 17 males and 17 females. Follow up ranged from 2 to 54 months (average, 21 months). Twenty-four patients (29 ducts) had congenital NLDO, seven patients (11 ducts) had congenital syndromes associated with craniofacial abnormalities, and three patients (three ducts) had acquired NLDO. In patients with congenital NLDO without craniofacial abnormalities or syndromes, 22 of 29 eyes (76%) were cured with another three (10%) showing improvement. Only one of 11 (9%) eyes of patients with congenital craniofacial abnormality or syndrome experienced complete resolution and only four of 11 (36%) eyes showed improvement. Of the patients with acquired NLDO, two of three (67%) of the eyes were cured and one (33%) improved. CONCLUSIONS: Endoscopic DCR is safe and effective for most children, although patients with craniofacial abnormalities or syndromes are extremely difficult to cure. PMID- 17277629 TI - Arteriovenous malformations of the tongue: a spectrum of disease. AB - OBJECTIVES: To examine our vascular anomalies team's experience with tongue arteriovenous malformations (AVM) with specific emphasis on the spectrum on disease and surgical management. METHODS: Retrospective chart review of 11 patients (10 female, 1 male), discovered from 1997 to 2005 with histological, radiographic, and clinical characteristics consistent with tongue AVM. RESULTS: Four patients displayed advanced disease with malformations involving the tongue, floor of mouth, and neck. Contributions from multiple feeding arteries were identified by angiography as each patient reported a prior history of surgical or embolic procedures. These lesions required preoperative embolization and extensive resection with complex reconstruction (mean operating time, 10.9 hr). One patient had evidence of recurrent disease (mean follow-up, 24.6 mo). In contrast, seven patients presented with discreet tongue malformations with a single feeding lingual artery. These patients reported no prior intervention, required only one resection (mean operating time, 2.8 hr), and have shown no evidence of recurrence (mean follow-up, 11 mo). Slight histologic differences between advanced versus focal tongue AVM were identified. CONCLUSIONS: This study suggests that tongue AVM can occur within a spectrum of disease with different clinical presentations, radiographic findings, and histology among patients with focal versus advanced lesions. Inadequate treatment is thought to contribute to collateral flow and disease progression in advanced AVM, making further management difficult. However, focal tongue AVM may represent early lesions that are more amenable to surgical management. PMID- 17277630 TI - Fully implantable hearing aids in patients with congenital auricular atresia. AB - INTRODUCTION: Patients with congenital auricular atresia suffer from a conductive hearing loss (HL) with an air-bone gap of 50 to 60 dB. Conventional bone conducting or bone anchored hearing aids are treatment options with several disadvantages and a biophysical limitation of almost no sound attenuation in the skull bone. Surgical construction of the sound conducting apparatus has been performed by others and modified by us into a three-step procedure with in vivo prefabrication of the external ear canal and the tympanic membrane. Although the results improved after inauguration of our modifications, there still remains an air-bone gap that makes air conducting hearing aids necessary in many patients. Implantable hearing aids have been developed for patients with perceptional HL and normal middle ear function but not for patients with middle ear disease or malformation. OBJECTIVES: Our objectives were to improve the hearing results of auricular atresia. STUDY DESIGN: Prospective. METHODS: The surgical instruments, the transducer, and the operative technique of the only fully implantable hearing aid (Otologics Fully Implantable Middle Ear Transducer) clinically available were modified. They were implanted in five patients with congenital auricular atresia and their audiologic outcome evaluated. RESULTS: After activation and fitting of the devices, patients experienced an improvement of sound-field thresholds up to 50 dB HL. The mean functional gain in a three frequency pure-tone average was approximately 35 dB HL. CONCLUSIONS: This technique appears to provide a completely new dimension for the audiologic rehabilitation of patients with severe malformation of the middle ear. PMID- 17277631 TI - Natural course of retention cysts of the maxillary sinus: long-term follow-up results. AB - OBJECTIVES: Retention cysts of the maxillary sinus are an incidental finding on radiographs. These cysts usually appear as rounded, dome-shaped, soft tissue masses, most often on the floor of the maxillary sinus. The aim of this study was to investigate the long-term natural course of retention cysts of the maxillary sinus. METHODS: Between November 1997 and October 2002, 40 patients were incidentally found to have retention cysts of the maxillary sinus on Waters view films. Seventeen of these patients were followed for 38 to 102 (mean, 60) months. Medical records, endoscopic nasal examinations, and Waters view of all 40 patients were reviewed. The size of each retention cyst and the ratio of cyst size to antral size were measured. RESULTS: Of the 40 patients, 21 (52.5%) had cysts in the left maxillary sinus, 17 (42.5%) had cysts in the right maxillary sinus, and 2 (5%) had cysts in both sinuses. Thirty of the 43 (69.7%) cysts appeared to arise from the floor of the sinus. Cyst size ranged from 108 mm to 1,001 mm, and the ratio of cyst size to antral size ranged from 12.8% to 96.9%, as measured on Waters view. Follow-up Waters view films in 17 patients showed that seven cysts disappeared completely, two decreased in size, four showed no significant change in size, and five increased in size. CONCLUSIONS: Most retention cysts of the maxillary sinus spontaneously regressed or showed no significant change in size over the long term. These findings suggest that, in the absence of associated complications, "wait and see" may be the appropriate management strategy for these retention cysts. PMID- 17277632 TI - Endonasal endoscopic repair of Sternberg's canal cerebrospinal fluid leaks. AB - OBJECTIVES: Management of cerebrospinal fluid leaks or encephaloceles of Sternberg's canal is challenging. Transnasal visualization of this area is difficult, especially when large pneumatization is present. External approaches to this region involve aggressive surgery and are often associated with significant morbidity. The aim of the study was to assess the real effectiveness of an endoscopic endonasal approach for treating cerebrospinal fluid leaks of the lateral recess of the sphenoid sinus. STUDY DESIGN: The authors conducted a retrospective evaluation. METHODS: Clinical charts of patients with cerebrospinal fluid leaks and/or encephaloceles of Sternberg's canal treated at our institution were retrospectively reviewed. All these patients were managed with an endonasal endoscopic procedure. RESULTS: Fifteen patients (9 female and 6 male) were included in this study. Nine patients underwent a transethmoidal-pterygoidal sphenoidal approach with a multilayer reconstructive technique. No cerebrospinal fluid leak recurrences were observed during follow up (mean follow up 37.6 +/- 21.7 standard deviation months) CONCLUSIONS: The transethmoidal-pterygoidal sphenoidal approach provides a wide, safe, and direct route to the lateral recess of the sphenoid sinus. Multilayered reconstruction of the skull base defects must be considered the first option for this kind of lesion. PMID- 17277634 TI - Repair of a malleus-handle fracture using calcium phosphate bone cement. AB - We report a case of a 60-year-old woman who reported a popping sound in her left ear, induced by changes in pressure, since she pulled her index finger out of her ear canal after accidentally inserting it while washing her hair. Otoscopic examination revealed a wrinkled tympanic membrane and irregular malleus handle. An isolated malleus-handle fracture resulting from barotrauma was suspected. The fracture was repaired surgically using calcium phosphate bone cement. Postoperatively, the problem disappeared and her hearing recovered. This case is the first to demonstrate the efficacy of calcium phosphate bone cement for repairing a malleus-handle fracture. PMID- 17277633 TI - Analysis of salvage operation in head and neck microsurgical reconstruction. AB - In this study, we examined salvage operations after reexploration in head and neck reconstruction and analyzed ways to solve problems. Free flap reconstruction of the head and neck lesion was carried out for 513 cases in our hospital over the past 12 years. Twenty-one cases of reexploration were caused by postoperative thrombosis (4.1%). We could only salvage seven cases (33.3%) of 21 cases from flap thrombosis. All seven cases were included in the category of venous thrombosis, and they were undertaken within 3 days postoperatively. Our results have shown that once thrombosis occurs, there is little possibility of flap salvage, particularly 3 days after operation and in infectious cases. When no flow phenomena are observed and no flap salvage is deemed possible, aggressive treatment such as a second free flap or next pedicle flap should be chosen as soon as possible to avoid any delay in postoperative treatment. PMID- 17277635 TI - War, politics, and voice: the vocal fold paralysis of George Orwell. AB - BACKGROUND: In 1936, like many individuals who felt the menace of fascism, George Orwell traveled to Spain to lend his support to the cause of the Republic, battling a right-wing coup. Spain, during its Civil War, was an eye-opening experience for him, yielding insights that allowed, and even compelled him to write Animal Farm and 1984. Spain was also a close brush with death. In May of 1937, in a trench on a windswept ridge near Huesca, Orwell was shot through the neck by a sniper, leaving him with a paralyzed vocal fold. DESIGN: A thorough review of firsthand accounts of Orwell's injury and subsequent care was made. These are presented in the context of current knowledge of ballistics, penetrating neck trauma, and vocal fold paralysis. RESULTS AND CONCLUSION: Orwell survived largely because of the nature of his wounding with a high-velocity jacketed military round. His recovery followed a course in many ways typical for patients with vocal fold paralysis. His writings leave us a unique and extraordinary account of the experience of being shot, of the medical care of the day, of the handicap of paralytic dysphonia, and of survival and heroism under extraordinary circumstances. PMID- 17277637 TI - The clinicians' aspects of parathyroid adenomas. PMID- 17277638 TI - Nurses' reassessment of postoperative pain after analgesic administration. AB - OBJECTIVES: To identify when and how nurses reassess patients' pain after analgesic administration in the postoperative context. METHODS: Fifty-two nurses were observed caring for postoperative patients (N=364) in 2 surgical settings in a major metropolitan hospital. Seventy-four observation periods of 2 hours duration were studied. The research assistant observed nurses' activities in caring for the allocated patients', detailing behavioral and verbal responses onto audiotape. RESULTS: Of the 316 pain activities that occurred in 74 observation periods, 14 (4.4%) were reassessments after analgesic administration. Four themes were evident from the 14 reassessments: opportunistic reassessment, the use of simple questioning, a focus on surgical wound pain not procedural pain, and nurse-initiated reassessment. CONCLUSIONS: Despite the focus on meeting standards of care in the area of pain management, there was an extraordinary lack of patient reassessment by nurses after the administration of analgesics. Given the raised awareness internationally on assessment generally and a lack of evidence focused on reassessment after an intervention, this may explain why research is failing to identify shifts in pain severity scores and indeed patient pain. PMID- 17277639 TI - Quantification of analgesic use in children with sickle cell disease. AB - OBJECTIVES: The purposes of this study were: (1) to quantify analgesic use in children with sickle cell disease who were hospitalized for a vaso-occlusive episode, using the Medication Quantification Scale (MQS) and (2) to examine the relationships between pain intensity scores, number of painful areas marked on a body outline diagram, number of word descriptors of pain quality, and amount of analgesic medications administered. METHODS: Children (5 to 19 y) were asked daily to provide pain intensity ratings and describe the location and quality of their pain. The nursing flowsheets were also reviewed to determine the dose, routes, and the number of times analgesic medications were administered in the previous 24 hours. RESULTS: Mean worst pain intensity score on the day of admission was 84.0+/-9.9 (range 63.8 to 100) on the 0 to 100 Oucher numeric rating scale. The mean MQS score administered on the day of admission was 15.7+/ 4.9 (range 6 to 24). This score decreased significantly by 1.2+/-0.5 (P<0.0001; range 0.9 to 2.5) each day of hospitalization. Significant correlations were found between various pain characteristics and total MQS scores prescribed at time of admission. DISCUSSION: The MQS was a useful and sensitive measure to quantify analgesic use in patients with sickle cell disease who were hospitalized for an acute painful episode. The MQS score accounted for variations in the types of analgesic medications, routes of administration, dosing schedules, and opioid dosing requirements. PMID- 17277640 TI - The coexistence of neuropathic pain, sleep, and psychiatric disorders: a novel treatment approach. AB - The diagnosis and treatment of neuropathic pain may be complicated by comorbid conditions such as sleep disturbances, depression, and anxiety. The interrelationship between the index neuropathic pain state and these comorbidities is complex: comorbid conditions exacerbate pain, and in turn, pain exacerbates the comorbid conditions. Because comorbidities can negatively impact response to pain treatment, healthcare providers should assess comorbidities as part of the diagnostic work-up, and management strategies should be designed to treat the whole patient, not just the pain. Theoretically, therapies that not only reduce pain, but also improve sleep and reduce anxiety and depression can provide multiple benefits without the risk of increased side effects inherent in combination therapy. Anticonvulsants and antidepressants have demonstrated efficacy in improving neuropathic pain and positively impacting comorbid sleep and mood disturbances. Novel anticonvulsants that can address one or more comorbidities in addition to pain may represent viable treatment options for patients with neuropathic pain. PMID- 17277641 TI - Myofascial trigger points are very prevalent in patients with chronic tension type headache: a double-blinded controlled study. AB - OBJECTIVES: Myofascial pain syndromes due to trigger points (TrPs) are clinical entities, but more evidence is needed to evaluate TrP palpation. Chronic tension type headache (CTTH) is the most prevalent chronic headache with high socioeconomic costs. The primary aim was to study whether TrP palpation can distinguish patients with headache patients from healthy controls. DESIGN: Double blinded, controlled design. PATIENTS: Twenty patients with the diagnosis of CTTH, and 20 healthy age-matched and sex-matched control participants. RESULTS: TrP palpation revealed more TrPs in patients (N=17) versus controls (N=6) (P=0.0005). Referred pain was also more frequent in patients (N=17) versus controls (N=9) (P=0.04). Further, TrP palpation also identified a higher pain intensity than at a control point (CtP) in both groups (P=0.0001). Pain intensity at TrPs in patients was higher than in controls (P=0.0010), and CtPs were also more tender in patients than in controls (P=0.0167). For spontaneous electromyographic activity no difference between TrPs versus CtPs within or between groups could be detected. CONCLUSIONS: These findings suggest that active TrPs are much more frequent in CTTH than in controls and the number and pain intensity of TrPs may be used to distinguish between the 2 groups. Spontaneous electromyographic activity could not be demonstrated, and the underlying biology of TrPs is still unclear. PMID- 17277642 TI - The role of the fear-avoidance model in female workers with neck-shoulder pain related to computer work. AB - OBJECTIVE: This study explores the fear-avoidance model in a sample of women with neck-shoulder pain related to computer work who were still functioning at the workplace. Exploring this model in this population could produce starting points for new treatment approaches in occupational health. METHODS: Fifty-eight women with work-related neck-shoulder pain and 45 healthy controls were included. Differences in components of the fear-avoidance model between cases and controls were computed using t tests. In addition, correlations were calculated and structural equation modeling techniques were performed to investigate the fear avoidance model in the case group. RESULTS: In line with the fear-avoidance model, cases had lower performance levels and felt significantly more disabled compared with their controls but showed, in contrast to the model, significantly lower levels of catastrophizing thoughts. Of the fear-avoidance beliefs measures, all correlations were significant except, between catastrophizing and fear of movement. Fear-avoidance beliefs about work seem to play an important role in disability levels of work-related neck-shoulder pain patients as illustrated by the high(est) association with disabilities. The results of the present study also showed that the original fear-avoidance model proposed in people with work related neck-shoulder pain who are still functioning at the workplace could only be confirmed by 1 of the 3 fit indices. Interestingly, adding an extrapath between fear-avoidance beliefs and disability in the original model approached good model fit as shown by all 3 fit indices. DISCUSSION: In line with the fear avoidance model, the current results addressed the importance of pain-related fear in people with neck-shoulder pain disability related to computer work. Interestingly, and not in accordance with the fear-avoidance model, fear avoidance beliefs directly influence disability levels in the current sample; regardless of lower levels of performance that is, physical impairment. PMID- 17277643 TI - Perceived control and negative affect predict expected and experienced acute clinical pain: a structural modeling analysis. AB - OBJECTIVES: Risk factors for elevated levels of clinical and experimental pain have been shown to be independently predicted by the individual's perception of personal control, negative emotional states, and pain expectancy. In this study we examine the mutual simultaneous association of these factors in the experience of dental extraction pain. METHODS: Using structural equation modeling we examined the relationship between desired and predicted personal control, negative emotional state and the expectation of pain to predict worst treatment pain. A convenience sample of 381 patients receiving walk-in emergency dental treatment were enrolled. Half of the patients were randomly selected for generating the measurement model, the hold-out subsample was used to confirm the model. RESULTS: Overall fit indices were adequate for both models [chi(2)/df > or = 1.37, Comparative Fit Index (CFI) > or = 0.96, Standardized Root-Mean-Square Residual (SRMR) < or = 0.05, Root Mean Square Error of Approximation (RMSEA) < or = 0.06], coefficients of determination were meaningful (R(2) > or = 0.14), and factor loadings (beta's) were significant (P's < 0.001) for each step in both models. DISCUSSION: A sequential pathway was revealed wherein patients' desire for control over the aversiveness of treatment and their prediction of having control over those events (whether desired or not) facilitated a negative emotional state. Negative emotional state in turn influenced expected treatment pain and subsequently the level of treatment pain actually experienced. We conclude that the perception of personal control is a clinically important and cognitively-mediated factor that influences the level of acute pain experienced during stressful clinical procedures. PMID- 17277644 TI - Clinical predictors of success and failure for lumbar facet radiofrequency denervation. AB - OBJECTIVE: To determine the clinical factors associated with the success and failure of radiofrequency denervation of the lumbar facet joints. METHODS: Clinical data were garnered from 3 academic medical centers on 192 patients with low back pain who underwent radiofrequency denervation after a positive response to diagnostic blocks. Success was defined as >/=50% pain relief lasting at least 6 months. Factors evaluated for their association with outcome included duration of pain, opioid use, symptom location, paraspinal tenderness, pain exacerbated by extension/rotation (ie, facet loading), MRI abnormalities, diabetes, smoking, scoliosis, obesity, prior surgery and levels treated. RESULTS: The only factor associated with a successful outcome was paraspinal tenderness. Variables that correlated with treatment failure were 'facet loading,' long duration of pain, and previous back surgery. CONCLUSIONS: It is counterproductive to use 'facet loading' as the sole basis for choosing patients for facet interventions. In patients at high risk for treatment failure, taking additional steps to reduce the rate of false-positive screening blocks may improve outcomes. PMID- 17277645 TI - Cognitions related to chronic pain: revision and extension of the cognitive evaluation questionnaire. AB - OBJECTIVES: The assessment of cognitive reactions to chronic pain is less well developed than other areas of pain assessment. The aim of the first study was to revise the Cognitive Evaluation Questionnaire of Philips whereas the second study examined its properties and validity in a new sample of people with chronic pain. METHODS: The revised scale underwent item analysis in 87 undergraduates, all of whom had pain of at least 1-month duration during the previous year, and was correlated with Skevington's Beliefs about Pain Control Questionnaire and 3 ratings of pain severity over time. In a second study, 96 participants with chronic pain (50 females) completed the Revised Cognitive Evaluation Questionnaire, the Survey of Pain Attitudes-Brief, the Center for Epidemiologic Studies Depression Scale, and sections of the Sickness Impact Profile. Hierarchical regression examined the construct validity of the revised scales in relation to psychosocial functioning and depression. RESULTS: Results showed acceptable internal consistency in both samples, and significant correlations with pain severity and the beliefs scales in Study 1. In Study 2, all but 2 scales showed correlations with the measure of beliefs about pain. The hierarchical multiple regression results showed that only Disability belief predicted psychosocial functioning, whereas Control from the beliefs measure and the new revised Causal Rumination and Concern with Effects of Pain scales predicted the CES-D depression scores. DISCUSSION: The revised cognitive scales in themselves were significant predictors in Study 2, and their contribution was more effective for depression than for psychosocial functioning. The results showed promise for the revised scale and are discussed in relation to previous research, with recommendations for future research into the cognitive reactions of individuals with chronic pain. PMID- 17277646 TI - Can the sensory symptoms of restless legs syndrome be assessed using a qualitative pain questionnaire? AB - OBJECTIVES: The sensations of restless legs syndrome (RLS) are described as paresthesias and dysesthesias, sensations which also occur in neuropathic pain. Whether validated pain assessment tools can be used to measure the quality and severity of RLS sensations has not been explored. METHODS: Patients with RLS (n=25) completed the RLS severity scale of the International Restless Legs Syndrome Study Group, the McGill Pain Questionnaire (MPQ), and a Visual Analog Scale. Words chosen frequently were also compared with those describing different pain types. RESULTS: The International Restless Legs Syndrome Study Group RLS severity scale score correlated significantly with the Pain Rating Index, and number of words chosen derived from the MPQ, but not with the visual analog scale estimate of pain intensity. The words chosen by patients with RLS showed no significant correlation with words chosen by patients with either neuropathic or nociceptive pain. DISCUSSION: The quality and severity of the sensation of RLS can be measured on the MPQ, and severity calculated from MPQ indices correlates significantly with a standard RLS severity measure. Thus the nonpainful sensations of RLS appear to be a subclinical form of pain. PMID- 17277647 TI - A randomized controlled trial on the effectiveness of mild water-filtered near infrared whole-body hyperthermia as an adjunct to a standard multimodal rehabilitation in the treatment of fibromyalgia. AB - OBJECTIVES: To evaluate whether mild water-filtered near infrared whole-body hyperthermia (NI-WBH) produces an additional benefit when applied as an adjunct to a standard multimodal rehabilitation (MR) compared with MR only in patients with fibromyalgia (FM). METHODS: One hundred thirty-nine patients of a German inpatient rehabilitation hospital meeting the ACR 1990 criteria for FM were randomly allocated to NI-WBH (heating-up to 38.1 degrees C body core temperature followed by a 15 min heat retention period) and MR or MR only, twice a week over 3 weeks. Main outcome measures were affective and sensory pain assessed by a German version of the McGill Pain Questionnaire, measured at baseline, postintervention, 3 and 6 months postintervention and analyzed by intention to treat. RESULTS: Repeated measures analysis of covariance showed significant differences between groups for both primary outcome measures in favor of NI-WBH and MR compared with MR only (P<0.001 for affective pain, P=0.001 for sensory pain). Secondary analyses on pain intensity, FM-related quality of life and tender point assessment yielded similar results. Moderate effect sizes were observed for all outcome measures considered (range, 0.41 to 0.75). NI-WBH related side effects were observed in 14 of 69 participants (20%) but all disappeared in less than 30 minutes. DISCUSSION: The study indicates that NI-WBH is a worthwhile adjunct to MR in the treatment of FM. PMID- 17277648 TI - Fear of pain influences outcomes after exercise-induced delayed onset muscle soreness at the shoulder. AB - OBJECTIVES: This study investigated whether anxiety, fear of pain, or pain catastrophizing were predictive of pain-related outcomes after induced delayed onset muscle soreness (DOMS) at the shoulder. METHODS: Healthy participants (19 males and 23 females) were eligible for participation if they had (a) no history of neck or shoulder pain, (b) no sensory or motor impairments of the upper extremity, (c) not regularly participating in upper-extremity weight training, (d) not currently or regularly taking pain medication, and (e) no history of upper-extremity surgery. Participants completed self-report measures for fear of pain, pain catastrophizing, and anxiety. Then, participants underwent a standard fatigue protocol to induce DOMS in the shoulder external rotator muscles. Participants were reassessed 24 hours after DOMS induction on clinical and evoked pressure pain reports, muscle force production, self-report of upper-extremity disability, and kinesiophobia. Stepwise regression models considered sex, anxiety, pain intensity, fear of pain, and pain catastrophizing as outcome predictors. RESULTS: Fear of pain alone explained 16% (P=0.008) of the variance in clinical pain and 10% (P=0.047) evoked pressure pain intensity. Clinical pain intensity alone explained 11% (P<0.031) of the variance in muscle force production. Clinical pain intensity and fear of pain explained 50% (P<0.001) of the variance in upper-extremity disability, whereas fear of pain and sex accounted for 26% (P=0.005) of the variance in kinesiophobia. CONCLUSIONS: With the exception of muscle force production, fear of pain had a consistent influence on shoulder DOMS outcomes, even after controlling for pain intensity. This study suggests fear of pain may be a relevant psychologic factor to consider in clinical studies investigating the development and treatment of chronic shoulder pain. PMID- 17277649 TI - Quantifying allodynia in patients suffering from unilateral neuropathic pain using von frey monofilaments. AB - OBJECTIVES: The aim of this study is to investigate whether quantitative sensory testing with Von Frey monofilaments (VFMs) can be used for the quantification of allodynia in patients with chronic neuropathic pain, and how the pain threshold of affected skin differs from healthy skin. METHODS: Using VFMs, we aimed to determine the pain threshold in 22 patients suffering from allodynia as a consequence of a chronic unilateral neuropathic pain syndrome. We performed quantitative sensory testing according to the Method of Limits protocol. We used the patient's own contralateral side and 5 healthy control participants to obtain reference values. RESULTS: On the affected side, we found in 20 out of 22 patients that the pain threshold could be determined with the monofilaments. On average, these 20 patients indicated pain upon the application of monofilament with logarithmic nr. 4.56, whereas no pain threshold could be determined on the contralateral, unaffected side, and in the healthy control participants for any monofilament. DISCUSSION: We showed that although etiology and pathophysiology of allodynia vary individually, with VFMs the clinical symptom allodynia can be quantified in a simple and practical fashion in almost all patients. PMID- 17277650 TI - The influence of patients' and primary care practitioners' beliefs and expectations about chronic musculoskeletal pain on the process of care: a systematic review of qualitative studies. AB - OBJECTIVES: To review qualitative, empirical studies exploring the influence of patients' and primary care practitioners' beliefs and expectations on the process of care for chronic musculoskeletal pain. METHODS: A multidisciplinary review group searched 9 bibliographic databases. The group worked in pairs to screen titles and abstracts for relevance, to quality appraise relevant studies, to extract data from high-quality studies and to undertake a thematic analysis of this data. RESULTS: We identified 12,994 abstracts from our searches, of which we obtained 113 full-text articles as their abstracts contained insufficient information for us to decide on their eligibility. We appraised 22 qualitative studies, 15 of which were included in the analysis. Themes identified included; (1) beliefs about pain, (2) expectations of treatment, (3) trust, and (4) patient education. Both patients and practitioners wanted clear communication within the consultation and to be respected, but conflicts existed on nearly all other aspects of the consultation, some of which at present may seem insurmountable and may lead to difficulties in achieving positive outcomes. DISCUSSION: To tackle the challenges and conflicts identified within the review, change may have to occur, not just in individual patient and practitioner beliefs and behavior, but also at an organizational and system level, for example, changes in undergraduate and postgraduate education and changes in the organization and availability of health services. PMID- 17277651 TI - High-dose morphine for intractable phantom limb pain. AB - Phantom limb pain is difficult to treat as existing therapies have limited effectiveness and what works for one person may not work for another. This makes the fact that research is ongoing and advancing even more important to many people who have this problem. We are reporting a case of intractable phantom limb pain whose pain did not respond to usual line of treatment and only high dose of morphine made the patient totally pain free. PMID- 17277652 TI - Management of descending necrotizing mediastinitis using minimally invasive video assisted thoracoscopic surgery. AB - Early diagnosis and aggressive surgical drainage are very important for successful treatment of descending necrotizing mediastinitis (DNM). However, the surgical techniques used for DNM treatment remain controversial. The purpose of this study was to evaluate the effectiveness of video-assisted thoracoscopic surgery (VATS) and cervical drainage for the management of DNM. Nine patients diagnosed with DNM were treated from May 2001 to April 2004. The mean age of the patients was 51.1+/-15.0 years. VATS and cervical drainage, including debridement and drainage of the mediastinum and pleura, were performed simultaneously. The mean postoperative hospital stay was 20.6+/-6.6 days. One patient (11%) died of sepsis and renal failure on the 15th postoperative day. Minimal mastication difficulty developed in 2 patients (22%). The mean postoperative follow-up period was 28.7+/-14.7(5 to 52) months. All the survivors are in good health with no recurrences. VATS was safe, effective, and a less invasive surgical option for the management of DNM and should be considered as a good alternative therapeutic modality. PMID- 17277653 TI - Prospective randomized trial on low-pressure versus standard-pressure pneumoperitoneum in outpatient laparoscopic cholecystectomy. AB - Inpatient low-pressure pneumoperitoneum laparoscopic cholecystectomy (LPLC) has been shown to have less postoperative pain (especially shoulder-tip pain). No report so far has documented the use of lower-pressure pneumoperitoneum in outpatient laparoscopic cholecystectomy (LC). A prospective randomized trial was conducted in Tung Wah Hospital, Day Surgery Centre from January 2004 to December 2004. A total of 40 patients were recruited and 20 of whom were allocated to each arm. Outcome measures included operation time, treatment-related morbidity, mortality, postoperative pain (eg, shoulder-tip pain), consumption of analgesics, and level of satisfaction. All patients in both groups could be discharged on the same day. Patients' demographics and operation time were comparable in both groups. There were no treatment-related morbidity and mortality, nor was there any significant difference in postoperative pain. Less shoulder-tip pain was observed in the LPLC group though without significant difference (5% vs. 20%; P=0.151). Three patients in the LPLC group needed higher insufflation pressure (12 mm Hg) because of inadequate exposure and adhesions, and the operations were successful in all of them. Otherwise, no conversion to open procedure was noted in both groups. The consumption of analgesics was minimal and a high level of satisfaction was achieved in both groups of patients. The present study demonstrated no difference in LPLC and standard-pressure pneumoperitoneum laparoscopic cholecystectomy in the outcomes of outpatient LC. Routine use of lower-pressure pneumoperitoneum in outpatient LC would not be recommended unless in selected straightforward cases. PMID- 17277654 TI - Laparoscopy-assisted distal pancreatectomy with mobilization of the distal pancreas and the spleen outside the abdominal cavity. AB - Laparoscopic ligation of the peripancreatic vessels or duct requires a particularly skillful technique. If the pancreatic tail and the spleen can be mobilized outside of the abdominal cavity, surgeons can perform these procedures as easily as ordinary open surgery. We developed a novel approach to laparoscopy assisted distal pancreatectomy without hand-assist. In brief, the pancreatic tail and the spleen were mobilized laparoscopically from the retroperitoneum until the celiac axis was exposed, then the pancreatic tail and the spleen were laparoscopically mobilized outside the peritoneal cavity from a small incision at the upper abdomen. After mobilization, the distal pancreatectomy was performed as usual open method. This approach offers better results in coping with organs, which seem to be difficult to resect through laparoscopic surgery alone. PMID- 17277655 TI - The role of tactile feedback in laparoscopic surgery. AB - Two experiments aiming at comparing palpation with gloved fingers, conventional laparoscopic instruments, and a laparoscopic instrument with a sensor array attached to its end effector are described. The sensor array provides the surgeon with visually presented tactile information. Fifteen subjects were asked to discriminate hardness and size of objects (rubber balls hidden in pig's intestine) with the 3 palpation methods. The experiments showed that the gloved fingers are better at differentiating hardness and size compared with conventional laparoscopic instruments and the instrument with sensor. There was no significant difference between conventional instruments and the instrument with sensor, although the results showed a higher average score with the instrument with sensor. This indicates that visual presentation may not be an ideal way of presenting tactile information. It also indicates that the presence of the array does not make the task more difficult. PMID- 17277656 TI - Laparoscopic Collis gastroplasty and Nissen fundoplication for reflux esophagitis with shortened esophagus in Japanese patients. AB - BACKGROUND: There is an extremely small number of surgical cases of laparoscopic Collis gastroplasty and Nissen fundoplication (LCN procedure) in Japan, and it is a fact that the surgical results are not thoroughly examined. PURPOSE: To investigate the results of LCN procedure for shortened esophagus. PATIENTS AND METHODS: The subjects consisted of 11 patients who underwent LCN procedure for shortened esophagus and followed for at least 2 years after surgery. The group of subjects consisted of 3 men and 8 women with an average age of 65.0+/-11.6 years, and an average follow-up period of 40.7+/-14.4 months. Esophagography, pH monitoring, and endoscopy were performed to assess preoperative conditions. Symptoms were clarified into 5 grades between 0 and 4 points, whereas patient satisfaction was assessed in 4 grades. The use of postoperative acid-reducing medication and the recurrence of esophagitis were also investigated. RESULTS: None of the patients experienced intraoperative complications, received transfusions, required conversion to open surgery, or died postoperatively. The average preoperative heartburn, regurgitation, and dysphagia scores were 2.36+/ 1.29, 2.27+/-1.19, and 1.82+/-1.78 points, respectively. These scores improved after surgery to 0.55+/-1.21 (P=0.0063), 0.55+/-1.21 (P=0.0094), and 1.0+/-1.18 (P=0.1236) points, respectively. All patients had esophagitis preoperatively, which recurred in 3 patients (27%). In these 3 patients, acid-secreting mucosa was confirmed on the oral side of the wrap, by positive Congo-red staining. Hiatal hernia recurred in one patient, who also experienced recurrent esophagitis. Five patients received acid-reducing medication postoperatively. The degree of satisfaction was excellent in 2, good in 6 patients, fair in 2, and poor in 1 patient(s). CONCLUSIONS: Although the LCN procedure can be performed safely, the outcome was not necessarily satisfactory. The LCN procedure requires avoidance of residual acid-secreting mucosa on the oral side of the wrapped neoesophagus. If acid-secreting mucosa remains, continuous acid suppression therapy should be employed postoperatively. PMID- 17277657 TI - Telerobotic-assisted laparoscopic right hemicolectomy: lateral to medial or medial to lateral dissection? AB - BACKGROUND: We previously reported that telerobotic-assisted laparoscopic colectomy was feasible and could be accomplished safely. Nonetheless, we found that the current iteration of da Vinci was not well suited to a lateral to medial (LtM) dissection of the colonic mesentery. The motion scaling made the large excursion arcs required for adequate exposure in a LtM dissection cumbersome to achieve. AIM: As a result, the aim of this study was to compare the ability of the da Vinci telerobotic surgical system to perform telerobotic-assisted laparoscopic right hemicolectomy using a LtM dissection with a medial to lateral (MtL) dissection technique. METHODS: We compared 8 consecutive da Vinci-assisted laparoscopic right hemicolectomies performed using a LtM dissection to 8 consecutive operations using a MtL dissection technique. Results were compared using analysis of variance. RESULTS: Age for the 2 groups were not significantly different: LtM 64 (43 to 71) years and MtL 56 (39 to 68) years. Body mass index was similar: LtM 27 (22 to 34) and MtL 25 (20 to 32) kg/m. Total surgical time (including cystoscopy and intraoperative colonoscopy) were similar: LtM 212 (188 to 610) minutes and MtL 203 (135 to 220) minutes. There was no significant difference in lymph node harvest: LtM 12 (3 to 20) lymph nodes and MtL 18 (3 to 35) lymph nodes. There were no deaths or anastomotic leaks in either groups. Median length of stay was similar for both groups: LtM 5 (3 to 10) days and MtL 4 (2 to 9) days. CONCLUSIONS: da Vinci-assisted laparoscopic right hemicolectomy using a MtL dissection technique achieves similar outcomes as a LtM dissection approach. PMID- 17277658 TI - The use of bioabsorbable staple line reinforcement for circular stapler (BSG "Seamguard") in colorectal surgery: initial experience. AB - Of all the complications associated with colorectal surgery, the most devastating and constant, despite all techniques being performed properly is anastomotic leakage, especially in left colon and rectal resections with rates as high as 50% when the rectum is involved. In 2005, our center published the preliminary experience with the use of linear staple line reinforcement for colon surgery. The purpose of this paper is to present a series of cases using a new conformation of bioabsorbable reinforcement for circular staplers in 5 patients, 2 patients with rectal cancer, 2 patients with diverticular disease, and 1 patient with sigmoid cancer. These initial data are very promising and has encouraged us to continue using this device on further patients. PMID- 17277659 TI - Elective laparoscopy in diagnosis and treatment of recurrent small bowel obstruction. AB - BACKGROUND: To evaluate the feasibility, efficacy, and safety of laparoscopy in diagnosis and treatment of recurrent small bowel obstruction. METHODS: Retrospective analysis of 253 patients who underwent therapeutic laparoscopy for recurrent small bowel obstruction from June 1996 to May 2005 was carried out. Patients with acute small bowel obstruction, bowel obstruction due to tumor, and obstructed inguinal hernias were excluded from analysis. RESULTS: Laparoscopy diagnosed cause of obstruction in all except 3 (1.18%) patients. The etiology included adhesions (38%), incarcerated ventral incisional hernias (32%), Meckel diverticulum (7%), stricture (14%), volvulus (3%), intussusception (4%). One hundred sixty nine patients were managed totally laparoscopically with adhesiolysis. Therapeutic bowel intervention other than adhesiolysis was required in 84 patients, of which 33 procedures were performed totally laparoscopically and remaining 51 procedures were completed with laparoscopically guided target incision. Five patients required conversion to open celiotomy. Iatrogenic enterotomies occurred in 3 patients and small bowel perforation during manipulation occurred in 1 patient. Postoperative procedure-related complications were seen in 44 patients. There was one mortality due to postoperative arrhythmia and cardiac failure. CONCLUSIONS: Laparoscopic diagnosis and treatment of recurrent small bowel obstruction is feasible, safe, and can be performed electively in selected cases. PMID- 17277660 TI - Transdiaphragmatic approach to the thorax using mini-invasive devices. AB - Operative management of synchronous abdominal and thoracic pathology has traditionally used 2 separate incisions. The introduction of laparoscopic devices has allowed the development of new techniques. The feasibility of a laparotomy and transdiaphragmatic access to the pleural cavity using mini-invasive instruments is presented. Three patients underwent combined thoracic and abdominal procedure through a laparotomy and transdiaphragmatic access using mini invasive devices. The procedure was proposed for both elective and emergency procedures: the first to achieve histologic diagnosis and to perform resection of synchronous metastases, the latter in a trauma setting for control bleeding. The access was provided by a circumferential incision of 5 cm length at the periphery of the diaphragm, starting close to the esophageal hiatus and carried from behind forward 2.5 cm away from the lateral insertions of the diaphragm to the chest wall. After deflation of the lung a 30-degree-angled telescope, stapling instruments, and other devices were introduced through the diaphragm incision. We obtained good intraoperative view of the pleural cavity, safe removal of abdominal and pulmonary pathology at the same time, and early repair of the injured pleura with control of hemostasis. We had no associated mortality or postoperative complications. In the first 2 patients, histology confirmed complete removal of the lesion. No case of insufficient tissue for primary diaphragmatic closure was documented and none prosthetic material was required. The interesting aspect of this report lies in the combined management of abdominal and thoracic lesion through a laparotomy and transdiaphragm approach of the pleura using mini-invasive devices. Our series indicate that simultaneous thoracic and abdominal surgery is feasible and safe in selected patients. We feel that there is a considerable learning curve with this technique and future studies will have to prove the feasibility of this procedure. PMID- 17277662 TI - Brachial plexus injury with emphasis on axillary nerve paralysis after thoracoscopic sympathicotomy for axillary hyperhidrosis. AB - Thoracic sympathicotomy for the treatment of axillary hyperhidrosis with the use of 2 mm thoracoscope and instruments is a simple and safe procedure. Nerve paralysis of any type after thoracic sympathicotomy is an extremely rare event. We report a 44-year-old woman who developed brachial plexus injury of her left arm after thoracoscopic sympathicotomy for axillary hyperhidrosis. The lesion involved the whole arm. All nerves of the brachial plexus except the axillary nerve recovered quickly. An axillary nerve type lesion was observed for 7 weeks, until the patient fully recovered all functions of her arm. The mechanism is believed not to be caused by the procedure itself, but by dorsal overextension of the abducted arm during the operation. PMID- 17277661 TI - Laparoscopic repair of incarcerated low spigelian hernia with transperitoneal PTFE DualMesh. AB - There are different types of hernias that can develop at certain sites in the abdominal wall. Spigelian hernia (SH) is a protrusion of abdominal contents through a defect in the spigelian aponeurosis, in proximity to the external margin of the rectus muscle. Usually, abdominal wall hernia sac contains the omentum but may also contain small intestine that might become trapped in the hernia. When ischemia of herniated contents is suspected, urgent surgical treatment is advocated. Elective laparoscopic repair of SH is still under discussion. However, a recent randomized study comparing open and laparoscopic repair as elective treatment suggested that extraperitoneal laparoscopic repair is the technique that offers best results for the patients. Recent development of new biologic materials and technologies in laparoscopy has led to improved results. We report the successful repair of incarcerated low SH that was successfully managed by urgent laparoscopic intraperitoneal onlay polytetrafluoroethylene mesh hernioplasty. PMID- 17277663 TI - Laparoscopic pyelolithotomy with intraperitoneal ultrasonic lithotripsy: report of a novel minimally invasive technique for intracorporeal stone ablation. AB - We present the case of a 71-year-old Hispanic woman with a 4-cm stone in the renal pelvis of a kidney with thin parenchyma. Retrograde pyelography revealed a normal ureter and normal ureteropelvic junction. A ureteral stent was placed. Six weeks after the stent was placed, a differential renal scan revealed 18% function of the involved kidney. A percutaneous nephrolithotomy was not performed because of the thin parenchyma and intrarenal anatomy, which would have complicated access. The patient underwent an uncomplicated laparoscopic pyelolithotomy. The stone was placed into an Endocatch entrapment sack. The open end of the Endocatch sack was brought through a trocar site, and a nephroscope and ultrasonic lithotripter were deployed. The stone was fragmented and aspirated in the standard manner, thereby avoiding the need to extend the 12-mm trocar incision for stone extraction. The stone fragmentation and extraction time was 14 minutes. The patient was stone-free and discharged home in the morning of the first postoperative day without complications. PMID- 17277664 TI - Video-assisted thoracoscopic surgery for catamenial hemoptysis: the rationale of preoperative computed tomography-guided hook-wire localization. AB - Catamenial hemoptysis is a rare disease. Hormone ablation therapy is the treatment of choice with multiple side effects. We report a case of pulmonary endometriosis with deep and changeable focus. Successful treatment was obtained with the combine use of computed tomography-guided hook-wire localization and video-assisted thoracoscopic surgery. Owing to benign and curable in nature, we suggest a more aggressive attitude toward this disease before proceeding to hormone ablation therapy. The role of preoperative localization in the management of such disease was also discussed. PMID- 17277665 TI - Laparoscopic resection of type I choledochal cyst in an adult and Roux-en-Y hepaticojejunostomy: a case report and literature review. AB - Choledochal cysts are rare cystic dilatations of the extrahepatic biliary tree, the intrahepatic bile ducts, or both and carry a substantial risk of malignant transformation. Type I choledochal cysts, which involve the entire common hepatic and common bile ducts, represent 80% to 90% of these lesions. We report laparoscopic excision of symptomatic type I choledochal cyst in a 37-year-old woman, and review the literature. Laparoscopic excision of the extrahepatic biliary tree from the hepatic confluence to the anomalous pancreatobiliary junction with en bloc cholecystectomy and reconstruction with a Roux-en-Y hepaticojejunostomy was accomplished. Postoperative recovery was uneventful with a hospital stay of 3 days. She remains well and asymptomatic at 6 months of follow-up. Laparoscopic excision of choledochal cysts may be safely accomplished with a prompt recovery. Further experience with this approach in larger number of patients is justified and long-term follow-up data are needed. PMID- 17277666 TI - Complication of a percutaneous endoscopic gastrostomy tube causing duodenal ischemia. AB - A 33-year-old woman with a percutaneous endoscopic gastrostomy tube was admitted with bilious vomiting, 1 month after her feeding tube was replaced by a temporary Foley catheter. A computed tomography scan of her abdomen revealed a 4.5 cm by 7.5 cm fluid-filled structure in the distal duodenum surrounding the Foley feeding tube. Approximately 100 mL of fluid was aspirated from the Foley's balloon port. We hypothesized that the Foley catheter was flushed inappropriately through the balloon port, causing an iatrogenic ischemic duodenal injury. Conservative management was successful in the intensive care unit. This case highlights an unusual complication of percutaneous endoscopic gastrostomy tubes. In addition, it emphasizes the temporary nature of Foley catheters as replacement gastrostomy tubes, and the importance of training in the handling of feeding tubes. PMID- 17277668 TI - Melanotic nonpsammomatous trigeminal schwannoma as the first manifestation of Carney complex: case report. AB - OBJECTIVE: Melanotic schwannoma is a rare neoplasm, classifiable as a peripheral nerve sheath tumor, and differentiated from a typical schwannoma by heavy pigmentation. Psammoma bodies can be visualized in more than 50% of melanotic schwannomas. Half of patients with such "psammomatous melanotic schwannomas" have Carney complex, a dominantly transmitted autosomal disorder. Most recently, the tumor suppressor gene, PRKAR1A, coding for the Type 1alpha regulatory subunit of protein kinase A was found to be mutated in approximately half of the known Carney complex families. Although cranial schwannomas have been described in patients with Carney complex, their numbers are too small to be considered a definite part of the syndrome. Furthermore, only melanotic schwannomas with psammoma bodies are included as diagnostic criteria for Carney complex. The objective of this report is to communicate a case of trigeminal nonpsammomatous melanotic schwannoma as the first manifestation of Carney complex. CLINICAL PRESENTATION: A 34-year-old woman presented with odontalgia, right V3 hypoesthesia, V2 paresthesia, and diplopia. Magnetic resonance imaging scans of the brain revealed a small tumor with homogenous contrast in the right trigeminal pathway. INTERVENTION: We performed an extradural approach to the right cavernous sinus by a middle fossa approach. The lateral wall was opened between the cranial nerves, and a soft and black tumor was resected in a piecemeal fashion. Histology and immunohistochemical analysis of the tumor were compatible with melanotic schwannoma, but no psammomatous bodies were identified. Endocrine evaluation showed that this patient's symptoms fulfilled the diagnostic criteria of Carney complex, with lentiginosis, multiple breast ductal adenomas, multiple hypoechoic nodules on thyroid ultrasonography, and a 4 x 5-cm asymptomatic atrial cardiac myxoma, which was removed 15 days after the neurosurgery. Three months later, a recurrence of melanotic schwannoma was identified. Molecular analyses of genomic and somatic deoxyribonucleic acid from the patient found a 578 to 579delTG mutation of PRKAR1A. CONCLUSION: We present the unusual case of a nonpsammomatous trigeminal melanotic schwannoma associated with Carney complex, with confirmed PRKAR1A gene mutation. Our case highlights that neurosurgeons, in the presence of a melanotic schwannoma, should be aware of the features of the Carney complex because, in such cases, pre- and postoperative management is significantly affected. We also postulate that the absence of psammoma bodies or cranial localization do not exclude this diagnosis. PMID- 17277669 TI - Primary malignant melanoma of the cerebellopontine angle: a diagnostic dilemma: case report. AB - OBJECTIVE: To present a rare case of a primary malignant melanoma of the central nervous system presenting as a cerebellopontine angle (CPA) tumor and to delineate aspects of the clinical presentation and magnetic resonance imaging scan characteristics that may suggest this unusual condition. CLINICAL PRESENTATION: The clinical presentation consisted of a short duration of right sided sensorineural hearing loss, facial weakness, and ataxia in a previously healthy man. Brain magnetic resonance imaging scans showed a right-sided CPA tumor exhibiting shortening of T1 and T2 relaxation times, but overall neuroradiological features were not consistent with any commonly occurring CPA tumors. INTERVENTION: Gross total excision of the lesion was accomplished via a right suboccipital craniectomy. Histological examination revealed a malignant melanoma. A detailed search excluded extracranial primary melanoma. CONCLUSION: Correlation of clinical and imaging findings offer the most important clues in the diagnosis of such unusual primary malignant tumors of the CPA. A history of rapid onset of audiovestibular symptoms, presence of facial palsy, and shortening of T1 and T2 relaxation times on magnetic resonance imaging scans should arouse the clinician's suspicions. PMID- 17277670 TI - Rapidly growing dysembryoplastic neuroepithelial tumor: case report. AB - OBJECTIVE: During the past 15 years, the concept of dysembryoplastic neuroepithelial tumors has continued to evolve. We present an interesting case of dysembryoplastic neuroepithelial tumor that showed rapid growth during a short period of time. CLINICAL PRESENTATION: A 9-year-old boy had been experiencing intractable complex partial seizures since the age of 7 years. Magnetic resonance imaging scans demonstrated a well-demarcated 3.5-cm lesion with a 1.5-cm ring enhanced core in the left temporal lobe. One month later, the lesion had rapidly grown to occupy three times more space than on the first evaluation, with the ring-enhanced core reaching approximately five times its initial volume. INTERVENTION: A combined tumor removal and epileptogenic focus resection surgery was performed immediately. In the pathological examination, the presence of the specific glioneuronal element with a Ki-67 labeling index of lower than 1%, as well as the glial component with a Ki-67 labeling index of 8%, led to a postoperative diagnosis of dysembryoplastic neuroepithelial tumor, complex form. No adjuvant therapy was performed. Five years after surgery, there is no evidence of any recurrence and the boy continues to be seizure free without antiepileptic drugs. CONCLUSION: The lesion did not behave as a stable benign entity as it is generally accepted, and is, therefore, presented as an argument in favor of an early and complete resection. PMID- 17277671 TI - Pediatric intradural extramedullary synovial sarcoma: case report. AB - OBJECTIVE: The diagnosis of intradural synovial sarcoma has not been previously published. This report provides a summary of the literature on this tumor and on tumors arising in this location, as well as a description of this patient's clinical course. CLINICAL PRESENTATION: An 11-year-old girl presented with back pain and radiculopathy. A magnetic resonance imaging scan of the spine revealed a spinal intradural, extramedullary mass at L2-L4 and four additional nodules of enhancement. INTERVENTION: The mass was nearly totally resected. Radiation and chemotherapy were administered. Intracranial metastases became evident during treatment. The patient died of the disease 14 months after diagnosis. CONCLUSION: The rapid progression of leptomeningeal metastasis despite maximal treatment demonstrates the aggressive nature of the tumor and the need for further study. PMID- 17277672 TI - Deep brain stimulation of the globus pallidus for generalized dystonia in GM1 Type 3 gangliosidosis: technical case report. AB - OBJECTIVE: GM1 Type 3 gangliosidosis is a lysosomal storage disorder for which no specific treatment is available. It is characterized by progressive generalized dystonia, which is refractory to pharmacological treatment and results in severe disability and life-threatening complications. We performed bilateral pallidal stimulation in a patient with GM1 gangliosidosis and report the 12-month postoperative course. CLINICAL PRESENTATION: A 24-year old woman presented with genetically confirmed GM1 gangliosidosis, resulting in severe progressive generalized dystonia. INTERVENTION: Leads were implanted bilaterally into the internal part of the globus pallidus under stereotactic guidance. At follow-up visits, both the patient and the neurologists who performed the assessment were unaware of whether the neurostimulator was on or off. The patient was videotaped with a standardized protocol and scored by an independent expert. CONCLUSION: After 1 year of follow-up, double-blind comparison of the patient's status with and without neurostimulation showed a 20% improvement, with a significant functional benefit, but no change in disease progression. Although further studies are needed to evaluate this therapeutic approach, this report suggests that pallidal stimulation might be a promising treatment for dystonia caused by GM1 Type 3 gangliosidosis. PMID- 17277674 TI - The Creation of Adam by Michelangelo Buonarroti (1475-1564). PMID- 17277678 TI - Treatment of ruptured intracranial aneurysms: looking to the past to register the future. AB - OBJECTIVE: The outcomes reported in the International Subarachnoid Aneurysm Trial (ISAT), a multicenter, prospective, randomized trial to directly compare surgical clipping with endovascular coiling as treatments for ruptured intracranial aneurysms, have been misinterpreted by many to indicate the superiority of coiling to surgical clipping in all instances. To better understand the results of ISAT and their implications for practice patterns, we compared the ISAT results with the results of other published studies regarding the treatment of ruptured intracranial aneurysms. METHODS: Data from 19 published studies were compared with each other and with ISAT results. Outcomes examined were overall rates of mortality, rebleeding, poor outcome (disability and death), procedural complication rates, and rates of reoperation and nontotal occlusion. RESULTS: In the 19 published studies, mean procedural complication rates were similar (surgical clipping, 11%; endovascular coiling, 9%); ISAT did not report procedural complications. ISAT rates were within the range of the other studies for overall mortality, total rebleeding, and poor outcome. Reoperation rates in the other studies were similar to those of ISAT (endovascular coiling, 12.5%; surgical clipping, 3.4%). The ISAT rate for less than 100% occlusion for endovascular coiling (6%) was below the range in the other studies (8.3-70.4%). CONCLUSION: Discrepancies with the results of other published studies, procedural limitations in study design, and lack of some data endpoints and subgroup analysis raise concerns regarding extracting generalizations from the conclusions of ISAT. We think that the creation of a national registry would further the study of treatment of ruptured intracranial aneurysms. PMID- 17277679 TI - A population-based study of neurosurgical and endovascular treatment of ruptured, intracranial aneurysms in a small neurosurgical unit. AB - OBJECTIVE: Since the introduction of endovascular embolization, the optimal treatment of ruptured aneurysms has been debated. Much of this debate has been based on results from large neurovascular centers and may not be applicable to small neurosurgical centers with low annual aneurysm loads. We think that the results of small centers, such as ours, may also be of some interest. METHODS: This study included 286 patients treated endovascularly or operated on by the senior investigator (KW) before November 2004. They all had an angiographically verified aneurysm as the source of bleeding in the subarachnoid hemorrhage. Variables related to presentation, radiological findings, treatment, and outcome were recorded. RESULTS: A significantly higher proportion (66.3%) of the endovascular patients had complete or near-complete recovery (Glasgow Outcome Scale 5) compared with the surgically treated patients (47.8%). When clinical outcomes were dichotomized into favorable (Glasgow Outcome Scale 4-5) and unfavorable (Glasgow Outcome Scale 1-3), no difference was found between the two treatment groups. Treatment-related mortality or morbidity was equal. Significantly more patients were converted from endovascular to surgical treatment than vice versa. No surgically treated patients rebled, whereas four endovascular patients rebled from their previously treated aneurysm. CONCLUSION: At present in our hospital, the endovascular modality seems to yield a better clinical outcome than surgery and has become our treatment of choice. With increasing use and further refinement of the endovascular techniques, the difference in outcomes between the treatment modalities will probably change even further in favor of the endovascular technique. PMID- 17277680 TI - Foramen magnum meningiomas: clinical outcome after microsurgical resection via a posterolateral suboccipital retrocondylar approach. AB - OBJECTIVE: We analyzed a consecutive series of patients operated for a foramen magnum (FM) meningioma located on the ventral aspect of the medulla oblongata via a posterolateral suboccipital retrocondylar approach with regard to long-term surgical outcome. METHODS: Clinical data in a consecutive series of 25 patients experiencing a meningioma attached to dura of the anterior or anterolateral FM rim were retrospectively reviewed. RESULTS: The most common symptoms of the 19 women and six men (mean age, 59.2 yr) was cervico-occipital pain (72%) and gait disturbance (32%). Clinical examination revealed gait ataxia in 48% of the patients. As depicted from preoperative magnetic resonance imaging (MRI), dural attachment of the meningioma at the FM rim was anterior in 36% and anterolateral in 64% of cases. Tumor removal was accomplished via a posterolateral suboccipital retrocondylar approach in all patients. A Simpson Grade 2 resection was achieved in 96% of the patients. Permanent surgical morbidity and mortality rates were 8 and 4%, respectively. No tumor recurrence was observed after a mean follow-up period of 6.1 years (range, 1-14 yr) with clinical and MRI examination, and 80% of the patients have regained full daily activity. CONCLUSION: Anterior and anterolateral FM meningiomas that displace the medulla/spinal cord can be safely and completely resected via a posterolateral suboccipital retrocondylar approach. A tumor remnant should be left on critical neurovascular structures in cases with poor arachnoid dissection planes. PMID- 17277681 TI - Significant tumor volume reduction of meningiomas after stereotactic radiotherapy: results of a prospective multicenter study. AB - OBJECTIVE: Stereotactic radiosurgery (SRS) is well established in the treatment of cranial base meningiomas. Fractionated stereotactic radiotherapy (SRT) offers an additional treatment option. Data for radiological regression differ, ranging from 13 to 61%. Therefore, the aims of this prospective study were to quantitatively analyze tumor volume (TV) shrinkage and to calculate determining factors. METHODS: Eighty-four patients were examined under equal conditions before and after SRT. Fat-saturated axial T1-weighted contrast-enhanced magnetic resonance imaging scans with 1- to 3-mm slice thickness were used. After image fusion, TV was drawn in each slice to analyze TV shrinkage three-dimensionally by the planning system. RESULTS: Mean TV had shrunk by 33% at 24 months (P = 0.02) and by 36% at 36 months (P = 0.0007) after SRT. With regard to half-year intervals, TV reduction decreased continuously towards a steady state (P < 0.0001). Younger age (P = 0.001) and smaller TV (P = 0.01) are determining factors. There was no correlation between TV reduction, prescribed dose, histological classification, sex, or previous operations. CONCLUSION: Meningiomas shrink significantly after SRT. TV shrinkage declines towards a steady state, which is not yet defined. Younger age and smaller TV are determining factors. Previous operations, sex, prescribed dose, or histological subtypes do not affect TV shrinkage. Eighteen to 24 months after irradiation, when symptoms are clinically stable, is the best time for the first magnetic resonance imaging scans evaluating tumor control and shrinkage. PMID- 17277682 TI - Endoscopic resection of thoracic paravertebral and dumbbell tumors. AB - OBJECTIVE: Neurogenic paravertebral tumors are uncommon neoplasms arising from neurogenic elements within the thorax. These tumors may be dumbbell shaped, extending into the spinal canal or exclusively paraspinal. Generally encapsulated, they are located in the posterior mediastinum. In this report, we present our experience in the thoracoscopic resection of these tumors, including surgical technique and potential pitfalls. METHODS: A retrospective review of patients undergoing endoscopic surgery for paravertebral tumors was undertaken. Patient demographics, charts, operative reports, and pre- and postoperative images were reviewed. RESULTS: Between 1997 and 2004, 13 patients were treated thoracoscopically for paravertebral tumors in our departments. Our population consisted of four men and nine women. The median age was 44.9 years (range, 29-66 yr). Eight patients presented with pain, dyspnea, cough, and weakness. Five patients had tumors found incidentally. Sizes of the tumors varied from 3 to 9 cm. Final pathology included four neurofibromas, eight schwannomas, and one unclassified granular cell tumor. Gross total resection was achieved endoscopically in all cases. Three patients required a hemilaminectomy for resection of the intraspinal dumbbell component of the tumor during the same operation. The mean operative time was 229.5 minutes. The mean estimated blood loss was 371.1 ml. Postoperative morbidities included one each of tongue swelling, ulnar neuropathy, and intercostal hyperesthesia. The mean hospital stay was 2.8 days. CONCLUSION: Paravertebral tumors in the posterior mediastinum are amenable to endoscopic removal, even in hard to reach locations. Tumors with intraspinal extension can be removed concurrently by performing a hemilaminectomy, followed by thoracoscopy, without the need for a thoracotomy. PMID- 17277683 TI - Temporal lobe surgery for intractable epilepsy in children: an analysis of outcomes in 126 children. AB - OBJECTIVE: Temporal lobectomy is a well-established neurosurgical procedure for temporal lobe epilepsy. In this study, we conducted a retrospective review of children with drug-resistant temporal lobe epilepsy to evaluate seizure outcome after temporal lobe surgery. METHODS: We reviewed the medical records of 126 children who had surgery for temporal lobe epilepsy at The Hospital for Sick Children between 1983 and 2003. The records were examined for preoperative and intraoperative factors that could predict patient outcome after surgery. RESULTS: The mean age at seizure onset was 5.9 years. The mean seizure duration before surgery was 5.6 years. All patients had preoperative computed tomographic scans, magnetic resonance imaging scans, or both. The mean age at the time of surgery was 13.5 years. Sixty-two patients underwent left temporal resections and 64 patients underwent right temporal resections. The histopathology of the temporal resections revealed low-grade brain tumors in 65 children (52%) and cavernous malformations in four children. Ganglioglioma and astrocytoma were the most common tumors encountered. Mesial temporal sclerosis was found in 16 patients (13%), astrogliosis in 15 patients (12%), and cortical dysplasia in eight patients (7%). Postoperative follow-up of at least 2 years was available for 106 patients and ranged up to 13.0 years. Seventy-four percent of patients had an Engel Class I or II outcome. Patients with temporal lobe lesions had better outcomes compared with those without lesions (P < 0.05). Patients without a history of secondary generalization of seizures also had a better outcome when compared with those with secondary generalization. Complications in the form of contralateral homonymous hemianopsia, dysphasia, and infection were found in 5% of patients. Twelve patients had a second temporal lobe procedure for intractable recurrent seizures. After a second procedure, seven patients returned to a seizure-free state. CONCLUSION: Temporal lobe resections for epilepsy in children are effective and safe procedures, with a favorable impact on seizure control. Repeat temporal resections for recurrent seizures may also be effective in restoring a seizure-free outcome to children. PMID- 17277684 TI - Wartime traumatic cerebral vasospasm: recent review of combat casualties. AB - OBJECTIVE: Blast-related neurotrauma is associated with the severest casualties from Operation Iraqi Freedom (OIF). A consequence of this is cerebral vasospasm. This study evaluated all inpatient neurosurgical consults related to battle injury from OIF. METHODS: Evaluation of all admissions from OIF from April 2003 to October 2005 was performed on patients with neurotrauma and a diagnostic cerebral angiogram. Differences between patients with and without vasospasm and predictors of vasospasm were analyzed. RESULTS: Fifty-seven out of 119 neurosurgical consults were evaluated. Of these, 47.4% had traumatic vasospasm; 86.7% of patients without vasospasm and 80.8% of patients with vasospasm sustained blast trauma. Average spasm duration was 14.3 days, with a range of up to 30 days. Vasospasm was associated with the presence of pseudoaneurysm (P = 0.05), hemorrhage (P = 0.03), the number of lobes injured (P = 0.012), and mortality (P = 0.029). Those with vasospasm fared worse than those without (P = 0.002). The number of lobes injured and the presence of pseudoaneurysm were significant predictors of vasospasm (P = 0.016 and 0.02, respectively). There was a significant quadratic trend towards neurological improvement for those receiving aggressive open surgical treatment (P = 0.002). In the vasospasm group, angioplasty with microballoon significantly lowered middle cerebral artery and basilar blood-flow velocities(P = 0.046 and 0.026, respectively). CONCLUSION: Traumatic vasospasm occurred in a substantial number of patients with severe neurotrauma, and clinical outcomes were worse for those with this condition. However, aggressive open surgical and endovascular treatment strategies may have improved outcome. This was the first study to analyze the effects of blast related injury on the cerebral vasculature. PMID- 17277685 TI - Pain syndromes after missile-caused peripheral nerve lesions: part 1--clinical characteristics. AB - OBJECTIVE: To report on the clinical characteristics of pain and factors influencing pain intensity in patients with missile-caused nerve injuries. METHODS: The prospective study included 326 patients with clinically significant pain syndromes including complex regional pain syndrome Type II, deafferentation pain, reinnervation pain, and neuralgic pain. Diagnostic procedures were analyzed, factors influencing the pain intensity were identified, and the patients' characteristics, pain characteristics, and other clinical symptoms and signs were compared between different types of pain syndromes. RESULTS: The rate of painful injuries ranged from 17.3 to 22.9% for mixed nerves and from 2.6 to 4.6% for motor nerves. Peripheral nerve block and sympathetic block were useful and safe adjuvant diagnostic procedures, obtaining pain relief in 66.7% of patients with neuralgic pain and in 90.1% of patients with complex regional pain syndrome Type II. Pain started 2.6 days after injury in patients with complex regional pain syndrome Type II and 11.9 days after injury in patients with painful nerve adhesions (analysis of variance, P < 0.001). Permanent pain was more frequent (79.1%) than paroxysmal pain, superficial pain was more frequent (55.2%) than deep pain, and burning pain was the most frequent pain descriptor (43.6%). Ten factors were found to significantly influence the pain intensity (binary logistic analysis), including three independent predictors (multivariate analysis): type of pain syndrome (P < 0.001), multiple nerve damage in the injury site (P = 0.022), and onset of pain in the first two days after injury (P = 0.031). CONCLUSION: Pain syndromes after missile-caused nerve injury differ significantly regarding time of pain onset, pain characteristics, and other symptoms and signs. The type of pain syndrome, multiple nerve damage, and early onset of pain are independent predictors of initial pain intensity. Although medical history and physical examination are the main diagnostic keys, nerve exploration preceded by a nerve block and sympathetic block are safe and useful adjuvant diagnostic procedures. PMID- 17277686 TI - Pain syndromes after missile-caused peripheral nerve lesions: part 2--treatment. AB - OBJECTIVE: To analyze treatment procedures and treatment outcomes of painful missile-caused nerve injuries and factors influencing the outcome. METHODS: The study included 326 patients with clinically significant pain syndromes, including complex regional pain syndrome Type II, deafferentation pain, reinnervation pain, and neuralgic pain. Treatment modalities included drug therapy, nerve surgery, sympatholysis, and dorsal root entry zone operation. Pain intensity was assessed before and after the treatment using a visual analog scale, and treatment outcome was defined as successful (pain relief >70%), fair (pain relief between 50 and 69%), or poor (pain relief <50%). The outcome was compared between different pain syndromes and different treatment modalities. RESULTS: A successful outcome was achieved in 28.6% of patients with deafferentation pain, in 76.9% of patients with complex regional pain syndrome Type II, and in 87.9 to 100% of patients with other pain syndromes (P = 0.002). Each type of pain syndrome required a specific treatment algorithm, but average pain relief was similar for all definitive treatment modalities (range, 81-88%; P > 0.05). Ten factors were found to significantly influence the treatment outcome, but only three factors were independent predictors of a successful outcome: type of pain syndrome (P < 0.001), severity of nerve injury (P < 0.001), and absence of pain paroxysms (P = 0.03). CONCLUSION: The treatment outcome of painful nerve injury depends on several factors, including the type of pain syndrome, severance of nerve injury, and absence of pain paroxysms. Drug therapy (carbamazepine, amitriptyline, or gabapentin) should be recommended, at least as a part of treatment, for patients with reinnervation pain, deafferentation pain, and complex regional pain syndrome Type II. Nerve surgery should be recommended for patients with posttraumatic neuralgia, either as the first treatment choice (acute nerve compression or intraneural foreign particles) or after unsuccessful pharmacological treatment (other causes of neuralgic pain). PMID- 17277687 TI - Trigeminal nerve radiosurgical treatment in intractable chronic cluster headache: unexpected high toxicity. AB - OBJECTIVE: We have previously reported short-term results of a prospective open trial designed to evaluate trigeminal nerve radiosurgical treatment in intractable chronic cluster headache (CCH). Medium- and long-term results have not yet been reported. METHODS: Ten patients presenting with a severe and drug resistant CCH were enrolled (nine men, one woman). The radiosurgical treatment was performed according to the technique usually used for trigeminal neuralgia in our department. A single 4-mm shot was positioned at the level of the cisternal portion of the trigeminal nerve. The median distance between the center of the shot and the emergence of the nerve was 9.35 mm (range, 7.5-13.3 mm). The median of this maximum dose to the brainstem was 8.0 Gy (range, 4.0-11.1 Gy). Mean age was 49.8 years (range, 32-77 yr). Mean duration of the CCH was 9 years (range, 2 33 yr). The mean follow-up period was 36.3 months (range, 24-48 mo). RESULTS: Two patients had complete relief of CCH. One patient had a good result with evolution in an episodic form. Seven patients had no improvement. Nine patients developed a new trigeminal nerve disturbance: three developed paresthesia with no hypoesthesia and six developed hypoesthesia, including two patients with deafferentation pain. Only one patient had neither paresthesia nor hypoesthesia. CONCLUSION: We confirmed, with medium- and long-term evaluation, the high rate of toxicity and failure of the technique. The high toxicity, despite a methodology identical to the one used in trigeminal neuralgia, leads us to suspect an underlying specificity of the nerve in CCH. We do not recommend radiosurgery for treatment of intractable CCH. PMID- 17277688 TI - Long-term results of radiosurgery for refractory cluster headache. AB - OBJECTIVE: Medically refractory cluster headache (CH) is a debilitating condition for which few surgical modalities have proven effective. Previous reports involving short-term follow-up of CH patients have reported modest degrees of pain relief after radiosurgery of the trigeminal nerve ipsilateral to symptom onset. With the recent success of deep brain stimulation as a surgical modality for these patients, it becomes imperative for the long-term risks and benefits of radiosurgery to be more extensively delineated. To address this issue, we present our findings from the largest retrospective series of patients undergoing radiosurgery for CH with extended follow-up periods. METHODS: Between 1997 and 2001, 10 patients with CH underwent gamma knife radiosurgery at our institution. All patients fulfilled clinical criteria for treatment, including complete resistance to pharmacotherapy (usually methysergide, verapamil, and lithium), pain primarily localized to the ophthalmic division of the trigeminal nerve, and psychological stability. The mean age at radiosurgery was 40.3 years (range, 26 62 yr), and the average CH duration was 11.3 years (range, 2-21 yr). Patients received 75 Gy to the 100% isodose line delivered to the most proximal part of the trigeminal nerve where the 50% isodose line was outside the brainstem (4-mm collimator), with a mean follow-up period of 39.7 months (range, 5-88 mo). Pain relief was defined as excellent (free of CH with minimal or no medications), good (50% reduction of CH severity and frequency with medications), fair (25% reduction of CH severity and frequency with medications), or poor (less than 25% reduction of CH severity and frequency with medications). RESULTS: After radiosurgery, pain relief was poor in nine patients and fair in one patient. Six patients with poor to fair relief initially experienced excellent to good relief (range, 2 wk-2 yr after treatment) before regressing. Five patients (50%) experienced trigeminal nerve dysfunction, manifesting predominantly as facial numbness after treatment. CONCLUSION: Although some patients may experience short term pain relief, none had relief sustainable for longer than 2 years. The results from this series indicate that radiosurgery of the trigeminal nerve does not provide long-term pain relief for medically refractory CH. PMID- 17277689 TI - Long-term results of microsurgical treatment of lumbar spinal stenosis by unilateral laminotomy for bilateral decompression. AB - OBJECTIVE: Laminectomy and bilateral laminotomy are the standard procedures for decompression of lumbar spinal stenosis (LSS). With the aim of less invasiveness and better preservation of spinal stability, the technique of unilateral laminotomy for bilateral decompression (ULBD) was developed. However, limited follow-up data exist to determine the efficiency and outcome of ULBD. Therefore, the authors present their 10-year experience with ULBD and postoperative long term results. METHODS: One hundred thirty-three consecutive patients (73 men and 60 women; mean age, 63 yr) meeting clinical and radiographic criteria for LSS who underwent first-time ULBD between 1994 and 1999 entered the study. The study parameters were set to ensure a follow-up period of at least 4 years. All patients were available for short-term follow-up re-evaluation within 3 months, and 102 (77%) of the 133 patients were available for long-term examination after a mean duration of 5.6 years. The scale of Finneson and Cooper was used for evaluation of the clinical results. RESULTS: One hundred thirty patients (97.7%) improved immediately after surgery. Ninety-four (92.2%) of the 102 patients available for long-term follow-up examination remained improved, and 85.3% had an excellent-to-fair operative result. The incidence of complications was 9.8%. Resurgery for complication was necessary in three patients, for restenosis in seven patients, and for spinal instability in two patients, accounting for a reoperation rate of 11.8%. CONCLUSION: ULBD allows achievement of good and long lasting operative results in patients with LSS. Postoperative deterioration, recurrences, and spinal instability are infrequent. For the authors, ULBD is the preferred technique to treat symptomatic LSS. PMID- 17277690 TI - In vitro study of biomechanical behavior of anterior and transforaminal lumbar interbody instrumentation techniques. AB - OBJECTIVE: To study the biomechanical behavior of lumbar interbody instrumentation techniques using titanium cages as either transforaminal lumbar interbody fusion (TLIF) or anterior lumbar interbody fusion (ALIF), with and without posterior pedicle fixation. METHODS: Six fresh-frozen lumbar spines (L1 L5) were loaded with pure moments of +/-7.5 Nm in unconstrained flexion extension, lateral bending, and axial rotation. Specimen were tested intact, after implantation of an ALIF or TLIF cage "stand-alone" in L2-L3 or L3-L4, and after additional posterior pedicle screw fixation. RESULTS: In all loading directions, the range of motion (ROM) of the segments instrumented with cage and pedicle screw fixation was below the ROM of the intact lumbar specimen for both instrumentation techniques. A significant difference was found between the TLIF cage and the ALIF cage with posterior pedicle screw fixation for the ROM in flexion-extension and axial rotation (P < 0.05). Without pedicle screw fixation, the TLIF cage showed a significantly increased ROM and neutral zone compared with an ALIF cage "stand-alone" in two of the three loading directions (P < 0.05). CONCLUSION: With pedicle screw fixation, the ALIF cage provides a higher segmental stability than the TLIF cage in flexion-extension and axial rotation, but the absolute biomechanical differences are minor. The different cage design and approach show only minor differences of segmental stability when combined with posterior pedicle screw fixation. PMID- 17277691 TI - Spectrum of genotype and clinical manifestations in cerebral cavernous malformations. AB - OBJECTIVE: Cerebral cavernous malformations (CCMs) are focal dysmorphic blood vessel anomalies predisposing individuals to hemorrhagic stroke and epilepsy. CCMs are sporadic or inherited as autosomal dominant disease with three known genes. The hypothesis that genetic heterogeneity would account for the remarkable variability in CCM manifestations was tested. METHODS: CCM cases were prospectively enrolled. Germline CCM1 gene mutations were sought in 89 CCM samples. Associations with clinical manifestations and lesion characteristics were made among 41 symptomatic familial cases, including one cohort of 26 cases with CCM1 mutations and a second cohort of 15 cases without identifiable CCM1 mutations. The 15 cases were screened for CCM2 and CCM3 mutations. RESULTS: CCM1 mutations were found in 34 out of 50 subjects with familial disease and in none of 39 sporadic CCM cases. CCM2 and CCM3 mutations were found in three out of 10 families screened without CCM1 mutations. Clinical manifestations in 22 Hispanic American cases with identical CCM1 mutations were highly variable. Fewer CCM1 patients experienced hemorrhage than others with familial disease (P = 0.0139 for all cases and P = 0.0442 for symptomatic cases). Adjusting for sex and age improved the logistic regression model, suggesting decreased numbers of patients with hemorrhage in CCM1 familial disease (P = 0.003 for all cases and P = 0.014 for symptomatic cases). Hemorrhage differences were not related to size or number of lesions. CONCLUSION: Factors in addition to CCM1 germline mutation contribute to CCM clinical manifestations. However, this evidence suggests that familial cases with CCM1 mutations may have less severe clinical manifestations than other familial cases. PMID- 17277692 TI - Diode laser-assisted carotid bypass surgery: an experimental study with morphological and immunohistochemical evaluations. AB - OBJECTIVE: Conventional suturing methods of microvascular anastomosis are associated with various degrees of vascular wall damage that can lead to thrombosis and bypass occlusion. An experimental model of double end-to-side venous graft anastomosis on the common carotid artery was set up to compare conventional suturing methods with a low-power diode laser vascular welding technique. METHODS: The experiments were performed on 40 rabbits that underwent implantation of a 15-mm segment of jugular vein on the common carotid artery. The proximal end-to-side suture was performed by eight interrupted stitches; the distal suture, which was done using a laser welding technique, was supported by four stay sutures. The animals were evaluated after 2 days (n = 15), 9 days (n = 15), and 30 days (n = 10). The vascular segments were excised and subjected to histological, immunohistochemical, and ultrastructural evaluation. RESULTS: The average clamping time to perform both anastomoses was 35 minutes. At the end of the follow-up period, one case of complete occlusion was observed after 9 days and one case was observed after 30 days. Surgical observations and pathological evaluation indicated that adoption of the laser welding technique reduced operative time and bleeding. Histologically, a reduction of thrombosis, inflammation, myointimal hyperplasia, and dystrophic calcification was observed in laser-assisted anastomoses. A better preservation of the endothelium was also evident in laser-treated anastomoses. The observed differences were deemed statistically significant (P < 0.05). CONCLUSION: Our study demonstrated the efficacy of diode laser welding in improving surgical techniques of high-flow bypass and in reducing the vascular wall damage observed with conventional methods. PMID- 17277693 TI - Treatment of malignant gliomas with mitoxantrone-loaded poly (lactide-co glycolide) microspheres. AB - OBJECTIVE: Mitoxantrone (MTZ) has potent in vitro activity against malignant glioma cell lines, but it cannot be used effectively as a systemic agent for the treatment of brain tumors because of its poor central nervous system penetration. However, MTZ-loaded poly(lactide-co-glycolide) (PLGA) microspheres may be injected into the peritumoral area and into tumor tissue to provide effective and sustained local drug concentrations without causing systemic side effects. METHODS: Fisher rats were randomized into three groups. The first group (n = 9) was concomitantly implanted with rat glioma (RG2) cells and blank PLGA microspheres. The second group (n = 6) was implanted with RG2 cells and MTZ loaded PLGA microspheres. The third group (n = 9) was implanted with RG2 cells, and MTZ-loaded PLGA microspheres were injected into the same area after 7 days. Animals were sacrificed on Day 15 or 35. Tumor volumes were measured after hematoxylin and eosin staining. Distribution kinetics of MTZ in the brain was determined by high-performance liquid chromatography in nine rats injected with MTZ-loaded microspheres. RESULTS: The tumor volumes were 76 +/- 11 and 107 +/- 11 mm (mean +/- standard error) on Days 15 (n = 6) and 35 (n = 3), respectively, in the control group. In rats treated with MTZ-loaded microspheres on Day 7, tumor volumes were significantly reduced to 17 +/- 4 and 23 +/- 2 mm on Days 15 (n = 6) and 35 (n = 3), respectively. No tumor formation was observed when glioma cells and MTZ-loaded PLGA microspheres were implanted concomitantly (n = 6). No systemic side effects or parenchymal inflammatory infiltration were observed in either group of rats. Brain MTZ concentration was highest at the injection site and declined with time and distance from the injection site and with time. CONCLUSION: These data demonstrate that MTZ-loaded PLGA microspheres can deliver therapeutic concentrations of drug to the tumor and prevent glioma growth without causing side effects. This treatment method may increase the efficiency of antineoplastic therapy and positively impact survival. PMID- 17277694 TI - Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice. AB - OBJECTIVE: To determine the effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth and associated angiogenesis in the brains of nude mice. METHODS: Human glioblastoma cells (10 U87MG cells) in 1 mul of medium were stereotactically injected during a 20-minute period into the caudate/putamen of nude mice. The mice were intraperitoneally treated daily with Cilengitide or solvent (control) beginning 5 days after tumor injection. The mice were sacrificed from 1 hour to 63 days after tumor implantation and examined for tumor size, vascularity, apoptosis, and cell replication. RESULTS: This injection technique resulted in a highly reproducible, localized, spherical tumor cell placement in the parenchyma without reflux into the subarachnoid space or penetration into the ventricle. Serial brain sections showed the tumor size remained unchanged at 1 to 2 mm for approximately 30 to 40 days. Thereafter, the control tumors showed exponential growth to a volume of 120 mm, with death of the mice at approximately 8 to 9 weeks. Serial staining for Ki-67, a marker for cell replication, and CD31, an indicator for angiogenesis, demonstrated an increase in proportion to the growth of the tumor. In contrast, the tumor volume in Cilengitide-treated mice stayed unchanged at 1 to 2 mm during the entire length of the experiment, with staining for Ki-67 and CD31 remaining low. CONCLUSION: This standardized brain tumor model is highly reproducible and useful for testing new treatment regimens. Cilengitide is highly effective in suppressing blood vessel growth, thereby controlling orthotopic growth of this glioblastoma cell line. PMID- 17277696 TI - Clarence Sumner Greene, Sr.: the first African-American neurosurgeon. AB - Largely because of the advances of the Civil Rights movement in the mid-20th century, an increasing number of African-Americans have had the opportunity to become physicians and enter the distinguished field of neurosurgery. Many have made the most of this opportunity, becoming prominent in both academics and private practice. Unfortunately, the details regarding the first African-American neurosurgeon, Clarence Sumner Greene, Sr., have remained in relative obscurity. Born on December 26, 1901 in Washington, D.C., Dr. Greene received his M.D. from the Howard University College of Medicine with distinction in 1936. After 7 years of general surgery residency and 4 years as a professor of surgery at Howard University, he was granted the opportunity by the legendary Wilder G. Penfield to train in neurosurgery at the world-renowned Montreal Neurological Institute from 1947 to 1949. Receiving high praise from Dr. Penfield, Dr. Greene became the first African-American certified by the American Board of Neurological Surgery on October 22, 1953. Subsequently, he was appointed as chair of neurosurgery at Howard University, where he successfully treated intracranial aneurysms, brain tumors, and herniated intervertebral discs until his tragic death in 1957. The diligence and perseverance of Clarence Sumner Greene, Sr., M.D., D.D.S., F.A.C.S. enabled him to overcome incredible odds to become the first African-American neurosurgeon, trained by Dr. Penfield at the Montreal Neurological Institute. A true pioneer, his achievements have opened the door for subsequent African Americans to enhance the field of neurosurgery. PMID- 17277697 TI - Friedrich-Christian Rosenthal: surgeon and anatomist. AB - Friedrich-Christian Rosenthal was a prominent German anatomist and surgeon. He was born in Greifswald, Germany on June 3, 1780. In his time, he was best known for his work on the olfactory system and ichthyology. However, his late work also led to his description of the eponymous canal in the cochlea and basal cerebral vein. After an itinerant academic, military, and professional career, he died of tuberculosis in Greifswald on December 5, 1829, working to the end on an unfinished treatise on the anatomy of the brain and cranial nerves. PMID- 17277695 TI - Metabolic remodeling of malignant gliomas for enhanced sensitization during radiotherapy: an in vitro study. AB - OBJECTIVE: To investigate a novel method to enhance radiosensitivity of gliomas via modification of metabolite flux immediately before radiotherapy. Malignant gliomas are highly glycolytic and produce copious amounts of lactic acid, which is effluxed to the tumor microenvironment via lactate transporters. We hypothesized that inhibition of lactic acid efflux would alter glioma metabolite profiles, including those that are radioprotective. H magnetic resonance spectroscopy (MRS) was used to quantify key metabolites, including those most effective for induction of low-dose radiation-induced cell death. METHODS: We inhibited lactate transport in U87-MG gliomas with alpha-cyano-4-hydroxycinnamic acid (ACCA). Flow cytometry was used to assess induction of cell death in treated cells. Cells were analyzed by MRS after ACCA treatment. Control and treated cells were subjected to low-dose irradiation, and the surviving fractions of cells were determined by clonogenic assays. RESULTS: MRS revealed changes to intracellular lactate on treatment with ACCA. Significant decreases in the metabolites taurine, glutamate, glutathione, alanine, and glycine were observed, along with inversion of the choline/phosphocholine profile. On exposure to low-dose radiation, ACCA pretreated U-87MG cells underwent rapid morphological changes, which were followed by apoptotic cell death. CONCLUSION: Inhibition of lactate efflux in malignant gliomas results in alterations of glycolytic metabolism, including decreased levels of the antioxidants taurine and glutathione and enhanced radiosensitivity of ACCA-treated cells. Thus, in situ application of lactate transport inhibitors such as ACCA as a novel adjunctive therapeutic strategy against glial tumors may greatly enhance the level of radiation-induced cell killing during a combined radio- and chemotherapeutic regimen. PMID- 17277699 TI - Alternatives to statins. Nonprescription options for lowering cholesterol. PMID- 17277700 TI - Cola consumption on a regular basis associated with lower bone density. PMID- 17277701 TI - Depression may go undiagnosed, untreated following stroke. PMID- 17277702 TI - Health benefits of eating fish outweigh potential risks. PMID- 17277703 TI - Rheumatoid arthritis. Help for aching joints. PMID- 17277704 TI - Mayo Clinic office visit. Addiction to pain medication. An interview with W. Michael Hooten, M.D. PMID- 17277706 TI - Do you need less sleep as you age? PMID- 17277705 TI - Everyday fitness. Staying active may help you live longer. PMID- 17277707 TI - I have asthma, and my doctor cautions against taking aspirin. Why? PMID- 17277708 TI - Women and screening. Preventing, detecting common health problems. PMID- 17277709 TI - Overview of trends in modern psychopharmacology. PMID- 17277710 TI - An association of intrusive, repetitive phrases with lamotrigine treatment in bipolar II disorder. AB - INTRODUCTION: Bipolar disorder is frequently associated with obsessional symptoms. However, no reports have identified a pattern of obsessionality that is associated with a specific mood stabilizer treatment. METHODS: A chart review was conducted on five patients with bipolar II disorder who spontaneously reported a form of obsessionality characterized by intrusive, recurrent phrases after taking lamotrigine. RESULTS: Development of the phrases occurred from 7-42 years after mood disorder onset and occurred only after initiation of lamotrigine treatment. The phrases improved with lamotrigine discontinuation or dose reduction and recurred with lamotrigine re-challenge or upon dose escalation. CONCLUSION: A possible mechanism for the development of the intrusive phrases involves the influence of lamotrigine on glutamatergic regulation in a bipolar II disorder population vulnerable to the expression of obsessionality. Limitations of this report include its observational nature, small number of cases reported, and confound of concomitant medication use. PMID- 17277712 TI - Compulsive buying disorder: a review of the evidence. AB - Compulsive buying disorder is characterized by excessive or poorly controlled preoccupations, urges, or behaviors regarding shopping and spending that lead to subjective distress or impaired functioning. Compulsive buying disorder is estimated to have a lifetime prevalence of 5.8% in the United States general adult population. In clinical settings, most individuals with compulsive buying disorder are women (approximately 80%). This gender difference may be artifactual. Compulsive buying disorder is typically chronic or intermittent, with an age of onset in the late teens or early 20s. Comorbid mood and anxiety disorders, substance use disorders, eating disorders, and other disorders of impulse control are common, as are Axis II disorders. The disorder occurs worldwide, mainly in developed countries with market-based economies, and it tends to run in families with mood disorders and substance abuse. There is no standard treatment for compulsive buying disorder, but group cognitive-behavioral models seem promising, and psychopharmacologic treatments are being actively studied. Other treatment options include simplicity circles, 12-step programs, financial counseling, bibliotherapy, marital therapy, and financial counseling. Directions for future research are discussed. PMID- 17277711 TI - Alzheimer's disease: progress in the development of anti-amyloid disease modifying therapies. AB - The amyloid hypothesis--the leading mechanistic theory of Alzheimer's disease- states that an imbalance in production or clearance of amyloid beta (Abeta) results in accumulation of Abeta and triggers a cascade of events leading to neurodegeneration and dementia. The number of persons with Alzheimer's disease is expected to triple by mid-century. If steps are not taken to delay the onset or slow the progression of Alzheimer's disease, the economic and personal tolls will be immense. Different classes of potentially disease-modifying treatments that interrupt early pathological events (ie, decreasing production or aggregation of Abeta or increasing its clearance) and potentially prevent downstream events are in phase II or III clinical studies. These include immunotherapies; secretase inhibitors; selective Abeta42-lowering agents; statins; anti-Abeta aggregation agents; peroxisome proliferator-activated receptor-gamma agonists; and others. Safety and serious adverse events have been a concern with immunotherapy and gamma-secretase inhibitors, though both continue in clinical trials. Anti-amyloid disease-modifying drugs that seem promising and have reached phase III clinical trials include those that selectively target Abeta42 production (eg, tarenflurbil), enhance the activity of alpha-secretase (eg, statins), and block Abeta aggregation (eg, transiposate). PMID- 17277714 TI - Psychosocial treatment of depression and suicidality in adolescents. AB - Depression is a common disorder among adolescents and is associated with a high risk of suicide. Suicide is the third leading cause of death among adolescents in the United States. Currently, there are only two evidence-based psychotherapies for adolescence depression: cognitive-behavioral therapy and interpersonal psychotherapy. Furthermore, psychosocial interventions that specifically target suicidal behavior in adolescents are even fewer in number than treatments for depression. This article will review the psychosocial interventions for depression and suicidality in adolescents and will describe a recently developed treatment that is under study for depressed suicidal adolescents. PMID- 17277715 TI - Do children and adolescents have differential response rates in placebo controlled trials of fluoxetine? AB - OBJECTIVE: Recent acute efficacy trials of antidepressants in youth have suggested that high placebo-response rates in children (< 12 years of age) indicate that children may be more responsive to non-specific treatment interventions. Yet, these studies generally have not presented age-specific outcome data. The objective of this study was to compare the efficacy outcomes for children (< 12 years of age) and adolescents (> or = 12 years of age) using the combined data from two previously published double-blind, placebo-controlled trials of fluoxetine. METHODS: Children (< 12 years of age) and adolescents (> or = 12 years of age) with major depressive disorder were randomized to fluoxetine or placebo for 8-9 weeks of treatment. Outcome was assessed using the Children's Depression Rating Scale-Revised (CDRS-R) and Clinical Global Impressions scale. RESULTS: Random regression of the CDRS-R showed a treatment group by age group interaction (F(1,338)=4.10, P=.044), indicating that the treatment effect was significantly more pronounced in children than adolescents. Within children, response at exit to fluoxetine was significantly better than placebo (56.9% vs 33.3%; P=.009). Adolescent response rates at exit were not significantly different between the groups (51.1% vs 38.6%; P=.128). Remission rates were low for both groups. CONCLUSION: In the combined fluoxetine trials, drug-placebo difference was greater in children compared with adolescents. Contrary to expectations, the placebo-response rate was lower in the children than the adolescents. PMID- 17277716 TI - Factors in the assessment of suicidality in youth. AB - Suicide remains a leading cause of death among youth, and suicide ideation and behavior are relatively common in both normal and clinical populations. Clinicians working with young people must assess for the presence of suicidal ideation, suicidal behavior, and other risk factors, in order to determine the level of risk. This paper provides the clinician with a summary of risk factors for youth suicide, as well as providing standardized terminology to enhance assessment of suicidal ideation and behavior. PMID- 17277717 TI - Recent advances in the treatment and management of excessive daytime sleepiness. AB - Excessive daytime sleepiness (EDS) is a prevalent complaint among patients in psychiatric care. Patients with conditions of EDS have often been misdiagnosed with depression due to their complaints of lack of energy, poor concentration, memory disturbance, and a reduced interest in life. Impaired alertness associated with EDS can be detrimental to a person's quality of life by causing decreased work performance, self-consciousness, low self esteem, and social isolation. Excessive sleepiness is also associated with various health problems, comorbid medical and psychiatric conditions, and fatal accidents occurring after the driver has fallen asleep at the wheel. Contributing factors leading to EDS range from insufficient sleep hours to central nervous system-mediated debilitating hypersomnolence. Circadian rhythm disorders, sleep disorders such as obstructive sleep apnea and narcolepsy, and medications that cause sleepiness may also contribute to symptoms of EDS. Recognition of the symptoms of sleep deprivation is essential, as many such patients do not have a clear awareness of their own sleepiness. Treatment options, depending upon the condition, include light therapy or appropriate airway management techniques such as nasal continuous positive airway pressure (CPAP). Occasionally, wakefulness-promoting medications are necessary, particularly in patients with narcolepsy. In this expert roundtable supplement, Stephen P. Duntley, MD, reviews the definition and prevalence of EDS and discusses the contributing factors and consequences of daytime sleepiness. Next, Richard K. Bogan, MD, FCCP, gives an overview of the differential diagnosis of EDS and the assessment tools available for identifying sleepiness in symptomatic patients. Finally, Mary B. O'Malley, MD, PhD, reviews treatment of EDS, including counseling on sleep hygiene and duration of sleep, mechanical treatments, bright-light therapy, and wake-promoting medications. PMID- 17277725 TI - Safety and efficacy of intravenous sodium valproate in the treatment of acute migraine. AB - This multicenter study investigated the safety and efficacy of intravenous valproate in acute migraine attacks and the possible impact of prophylactic valproate pre-treatment. Thirty-six patients established on migraine prophylaxis were administered 500 mg sodium valproate intravenously against acute migraine attacks. Pain development was assessed by visual analogue scale up to a 24 hours follow up interview to detect e.g. possible relapse symptoms. A subgroup analysis examined whether prophylactic treatment with valproate affected its acute anti migraine efficacy. A meaningful headache reduction within two hours was achieved in all 12 patients with and in 20 out of 24 patients without valproate prophylaxis. Headache-associated signs and symptoms were substantially reduced. No serious side-effects were reported. The results confirm the therapeutic value of intravenous valproate in acute migraine attacks described in literature and show a beneficial effect on all investigated efficacy parameters with a trend to even better response in patients receiving valproate prophylaxis. PMID- 17277726 TI - 18FDG PET in hallucinating and non-hallucinating patients. AB - OBJECTIVE: The aim of the study was to detect whether the abnormal regional brain activity correlates with auditory verbal hallucination-proneness (AVH) in a group of patients with schizophrenia and schizophrenia-related psychoses. METHODS: 15 patients with prominent AVH (score for hallucination intensity--item 3 in the PANSS > or =4) and 15 control patients without AVH (item 3 PANSS score < or =2) underwent 18FDG positron emission tomography at rest. RESULTS: SPM group analysis revealed an increased uptake of 18FDG in the right middle frontal gyrus (BA46) in subjects with high verbal hallucination score compared to non-hallucinating patients (p<0.001, uncorrected). Activation in BA46 positively correlated with the intensity of hallucinations (Spearman r=0.57; p<0.001). CONCLUSIONS: The observed functional recruitment of the right prefrontal cortex in subjects with high hallucination score may reflect impairment in the integration of intended actions and sensory feedback resulting in misattribution of internal events to an external source. This mechanism may form the cognitive basis for AVH. PMID- 17277727 TI - The endocrine profiles in men with localized and locally advanced prostate cancer treated with radical prostatectomy. AB - OBJECTIVE: Prostate cancer is now recognized as one of the principal medical problems facing male population and the commonest cancer in males in delevoped countries. The aim of this study was to find out whether serum hormone levels differ significantly in localized (pT2) and locally advanced (pT3-pT4 or N1) prostate cancer. METHODS: In 250 men (mean age+/-SEM: 63.8+/-0.4) who underwent radical retropubic prostatectomy for histologically confirmed prostate cancer were analyzed serum samples for total testosterone, dehydroepiandrosterone sulfate, estradiol, progesterone, prolactin, cortisol, sex hormone-binding globulin, luteinizing hormone and follicle stimulating hormone. Free testosterone content was calculated from total testosterone and SHBG concentrations. RESULTS: Significantly lower serum level of FSH, i.e. 5.63+/-0.31 vs. 7.07+/-0.65 U/L was found in patients with localized prostate cancer than in locally advanced (p<0.05). Significant correlation was found between serum levels of DHEAS and cortisol in both groups (p<0.02), estradiol and prolactin in patients with locally advanced prostate cancer, as well between LH and prolactin (p<0.05). No differences were found in other observed hormones. CONCLUSION: The results point to importance of hormone status as possible additional prognostic marker for patients with prostate cancer. Considerable research is needed to further understand influence of hormones on prostate cancer. PMID- 17277728 TI - Nitric oxide in prepubertal rat ovary contribution of the ganglionic nitric oxide synthase system via superior ovarian nerve. AB - Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. Considering the existence of the nitric oxide/ nitric oxide synthase system in the peripheral neural system and in the ovary, the aim of this work was to analyze if the liberation of NO in the ovarian compartment of prepubertal rats is of ovarian and/or ganglionic origin. The analysis is carried out from a physiological point of view using the experimental coeliac ganglion- Superior Ovarian Nerve--ovary model with and without ganglionic cholinergic stimulus Acetylcholine (Ach) 10(-6) M. Non selective and selective inhibitors of the synthase nitric oxide enzyme were added to the ovarian and ganglionic compartment, and the liberation of nitrites (soluble metabolite of the nitric oxide) in the ovarian incubation liquid was measured. We found that the non selective inhibitor L-nitro-arginina methyl ester (L-NAME) in the ovarian compartment decreased the liberation of nitrites, and that Aminoguanidine (AG) in two concentrations in a non-dose dependent form provoked the same effect. The addition of Ach in ganglion magnified the effect of the inhibitors of the NOS enzyme. The most relevant results after the addition of inhibitors in ganglion were obtained with AG 400 and 800 microM. The inhibition was made evident with and without the joint action of Ach in ganglion. These data suggest that the greatest production of NO in the ovarian compartment comes from the ovary, mainly the iNOS isoform, though the coeliac ganglion also contributes through the superior ovarian nerve but with less quantity. PMID- 17277729 TI - Effect of fluoxetine on circadian rhythm of melatonin in patients with major depressive disorder. AB - OBJECTIVES: The purpose of this study is to explore the response of melatonin circadian rhythm to fluoxetine treatment and its relationship with clinical therapeutic effect. METHODS: This study investigated salivary melatonin in 13 outpatients with major depressive disorder and age- and sex-matched healthy controls. Depressed patients received six weeks fluoxetine (20 mg/day) treatment, and saliva was collected before and four weeks after treatment. In sampling days, a total of 12 time-point salivary melatonin was measured over 24-hours. Multioscillator cosinor model was used to fit the rhythms. RESULTS: There was no difference of circadian melatonin rhythms in depressed patients, and melatonin was not significantly lower after fluoxetine treatment. To our surprise, the melatonin amplitude (Before minus After) was positively correlated with the improvement in Hamilton Depression Rating Scale (HDRS) scores at day 42 whereas there was no such correlation at day 28. CONCLUSIONS: Melatonin rhythms were similar between depressed patients and matched healthy controls. The interesting finding that the difference of salivary melatonin amplitude was correlated with the clinical improvement after six weeks fluoxetine treatment deserve further study. PMID- 17277730 TI - Increase in body weight is a non-motor side effect of deep brain stimulation of the subthalamic nucleus in Parkinson's disease. AB - Deep brain stimulation of the subthalamic nucleus (DBS STN) is an effective treatment method in advanced Parkinson's disease (PD) providing marked improvement of its major motor symptoms. In addition, non-motor effects have been reported including weight gain in PD patients after DBS STN. Using retrospective survey, we aimed to evaluate weight changes in our patients with advanced PD treated with DBS STN. We inquired 25 PD patients (16 men, 9 women), of mean age 55 (42-65) years, mean PD duration 15 (9-21) years, who previously received bilateral DBS STN. We obtained valid data from 23 patients. In the first survey, 1 to 45 months after DBS, weight gain was found in all patients comparing to pre DBS period. The mean increase was 9.4 kg (from 1 to 25 kg). The patients' mean body mass index (BMI) increased from 23.7 to 27.0 kg/m2, i.e. by 3.3 kg/m2 (+2 to +6.1 kg/m2). In the repeated survey one year later, in 12 of the patients body weight moderately decreased, 3 did not change, and 6 patients further increased their weight. Possible explanations of body weight gain after DBS STN include a reduction of energy output related to elimination of dyskinesias, improved alimentation or direct influence on function of lateral hypothalamus by DBS STN. PMID- 17277731 TI - Salivary alpha-amylase levels and hyperbolic discounting in male humans. AB - OBJECTIVE: Little is known regarding the role of the sympathetic-adrenal medullary (SAM) system in self-control and impulsivity in intertemporal choice (delay discounting), although the roles of dopaminergic and serotonergic systems have been extensively examined. This study was aimed to examine the relationships between salivary alpha-amylase (sAA, a non-invasive biological marker of adrenergic/SAM activities) levels and hyperbolic discounting, which is of interest in psychoneuroendocrinology and neuroeconomics. METHODS: We assessed degrees to which delayed monetary gains were discounted (hyperbolic discount rates) in healthy male students. Participants' sAA were also assessed. RESULTS: We observed negative relationships between sAA and hyperbolic discounting of small, medium, and large monetary gains. CONCLUSIONS: The results indicate that subjects with low sAA are impulsive in intertemporal choice. Implications for the roles of adrenergic and SAM systems in self-control in intertemporal choice are discussed. PMID- 17277732 TI - Lateralized electrodermal dysfunction and complexity in patients with schizophrenia and depression. AB - OBJECTIVE: Recent evidence indicates that in psychiatric patients with schizophrenia and depression, lateralized EDA changes linked to temporal-limbic electrophysiological dysfunction occur. These clinical findings provide evidence for brain asymmetry and disruptions related to integrative brain activity in pathological conditions. METHODS: These changes in brain asymmetry may be assessed by linear analysis of EDA measurement and nonlinear analysis of brain complexity calculated as information entropy. Two groups of patients with established diagnosis of paranoid schizophrenia (N=35), unipolar depression (N=35) and a control group of 35 healthy controls were examined by measurement of bilateral electrodermal activity (EDA). In non-linear data analysis of the EDA time series in resting state the method of recurrence quantification analysis was applied. RESULTS: In these patients significant right-left EDA asymmetry and asymmetry of information entropy calculated by non-linear recurrence quantification analysis of EDA records have been found. Similar asymmetry has not been observed in the group of healthy controls. CONCLUSIONS: Because information entropy reflects the complexity of the deterministic structure in the system, then unilaterally increased entropy in patients with schizophrenia and depression likely indicates specific nonlinear disturbances in limbic circuits that modulate EDA. These data are in accordance with recent findings that indicate apparent differences in nonlinear neural patterns in the psychiatric diseases and nonlinear behavior of healthy brain. PMID- 17277733 TI - Mood disorder in a patient with Smith-Magenis syndrome: a case report. AB - Smith-Magenis syndrome (SMS) is a microdeletion syndrome characterized by physical and neurobehavioural features. This report describes the case of a 27 year old female affected by SMS associated with a diagnosis, according to DSMIV criteria, of Mood Disorder N.O.S. and Intermittent Explosive Disorder. To our knowledge, the association of SMS with mood shifts has never been reported. Considering the genetic alterations that characterizes the SMS, further investigations on the region of the chromosome 17p11.2 could help produce more information on the role of melatonin in the genesis of mood disorder. PMID- 17277734 TI - The effect of repetitive transcranial magnetic stimulation (rTMS) add on serotonin reuptake inhibitors in patients with panic disorder: a randomized, double blind sham controlled study. AB - BACKGROUND: Transcranial magnetic stimulation (rTMS) can modulate cortical activity. The goal of our study was to assess whether rTMS would facilitate effect of serotonin reuptake inhibitors in patients with panic disorder. METHOD: Fifteen patients suffering from panic disorder resistant to serotonin reuptake inhibitor (SRI) therapy were randomly assigned to either active or to sham rTMS. The aim of the study was to compare the 2 and 4 weeks efficacy of the 10 sessions 1 Hz rTMS with sham rTMS add on SRI therapy. We use 1 Hz, 30 minutes rTMS, 110% of motor threshold administered over the right dorso-lateral prefrontal cortex (DLPFC). The same time schedule was used for sham administration. Fifteen patients finished the study,. Psychopathology was assessed using the rating scales CGI, HAMA, PDSS and BAI before the treatment, immediately after the experimental treatment and 2 weeks after the experimental treatment by an independent reviewer. RESULTS: Both groups improved during the study period but the treatment effect did not differ between groups in any of the instruments. CONCLUSION: Low frequency rTMS administered over the right dorso-lateral prefrontal cortex after 10 sessions did not differ from sham rTMS add on serotonin reuptake inhibitors in patients with panic disorder. PMID- 17277735 TI - Changes in Rx1 and Pax6 activity at eye field stages differentially alter the production of amacrine neurotransmitter subtypes in Xenopus. AB - PURPOSE: Both rx1 and pax6 are expressed during the initial formation of the vertebrate eye field, and they are thought to be crucial for maintenance of the retinal stem cells in the ciliary marginal zone. However, both genes continue to be expressed in different layers of the differentiating retina, suggesting that they have additional roles in cell type specification. Because previous work suggested that amacrine cell subtypes are derived from biased progenitors in the eye field, we tested whether altering Rx1 or Pax6 activity during eye field stages affects the production of three neurotransmitter subtypes of amacrine cells. METHODS: Gain-of-function and loss-of-function hormone-inducible constructs of Rx1 and Pax6 were used to alter Rx1 and Pax6 protein or activity levels after the formation of the eye field. The major-retina producing blastomere of the 32-cell stage Xenopus embryo (D1.1.1) was injected with mRNA encoding one of these proteins and mRNA encoding GFP to label the altered lineage. Embryos were treated with synthetic hormone at either early (stage 12) or late (stage 16) eye field stages and they developed to tadpole stages (stage 44/45) when the cells in the central retina have differentiated. Amacrine cell subtypes (dopamine [DA], neuropeptide Y [NPY], gamma aminobutyrate acid [GABA]) were detected by immunofluorescence histology and the numbers of each type of cell produced within the affected lineage were counted. The percent contribution of the D1.1.1 lineage to a particular amacrine subtype after stage 12 or stage 16 hormone treatment were independently compared to those from gfp mRNA-injected control embryos that were similarly treated with hormone. RESULTS: Increasing Rx1 at early eye field stages promotes NPY amacrine cells and represses GABA and DA amacrine cells, and at late eye field stages significantly represses DA and NPY phenotypes but has a diminished effect on the GABA phenotype. Increasing Pax6 at early eye field stages represses NPY and DA amacrine cells but does not affect the GABA phenotype, whereas in the late eye field it significantly represses only the DA phenotype. CONCLUSIONS: Rx1 and Pax6 differentially modify the ability of eye field precursors to produce different neurotransmitter subtypes of amacrine cells. These effects varied for each of the subtypes investigated, indicating that amacrine cells are not all specified by a single genetic program. Furthermore, some cases were time-dependent, indicating that the downstream effects change as development proceeds. PMID- 17277736 TI - Partial paternal uniparental disomy (UPD) of chromosome 1 in a patient with Stargardt disease. AB - PURPOSE: Stargardt disease (STGD) is the most common juvenile macular dystrophy, characterized by central visual impairment. All recessively inherited cases are thought to be due to mutations in the ABCA4 gene, mapped to 1p21-p13. METHODS: To describe a form of non-mendelian inheritance in a patient with STGD identified through the course of a conventional mutational screening performed on 77 STGD families. DNA from the patient and relatives was analyzed for variants in all 50 exons of the ABCA4 gene by screening on the ABCR400 microarray; results were confirmed by direct sequencing. Haplotype analyses, standard and high-resolution (HR) karyotypes, and multiplex ligation-dependent probe amplification (MLPA) were also performed. RESULTS: A patient with STGD caused by the homozygous p.Arg1129Leu mutation in the ABCA4 gene was found to be the daughter of a noncarrier mother and a father who was heterozygous for this change. Haplotype analysis suggested that no maternal ABCA4 allele was transmitted to the patient. Microsatellite markers spanning the entire chromosome 1 identified a homozygous region of at least 4.4 Mb, involving the ABCA4 gene. The cytogenetic study revealed normal female karyotype. Further evaluation with MLPA showed the patient had a normal dosage for both copies of the ABCA4 gene, thus suggesting partial paternal isodisomy but not a maternal microdeletion. CONCLUSIONS: We report that recessive STGD can rarely be inherited from only one unaffected carrier parent in a non-mendelian manner. This study also demonstrates that genomic alterations contribute to only a small fraction of disease-associated alleles for ABCA4. PMID- 17277737 TI - Large genomic rearrangements within the PCDH15 gene are a significant cause of USH1F syndrome. AB - PURPOSE: Protocadherin-15 (PCDH15) is one of the five genes currently identified as being mutated in Usher 1 syndrome and defines Usher syndrome type 1F (USH1F). When PCDH15 was systematically analyzed for mutations in a cohort of USH1 patients, a number of deletions were found. Here we characterize these deletions as to extent, position, and breakpoints. METHODS: Microsatellite and single nucleotide polymorphism (SNP) analyses, used in a preliminary survey of an Usher cohort of 31 patients, revealed large deletions in three patients. These deletions were further characterized by semiquantitative PCR assays to narrow down the breakpoints. RESULTS: The analysis of the three large deletions revealed that all six breakpoints are different. The breakpoint junction was identified in one patient and the four other breakpoints were mapped to 4 kb. There were no specific distinguishing features of the isolated breakpoints. CONCLUSIONS: A complete screen of PCDH15 should include a search for large deletions. Failure to screen for gross genomic rearrangements is likely to significantly lower the mutation detection rate. A likely explanation for the high rate of such deletions is the unusual gene structure. PCDH15 gene spans nearly 1 Mb for a corresponding open reading frame (ORF) of 7,021 bp. The intron sizes of PCDH15 are up to 150 kb, and the first three exons of the gene cover 0.42 Mb. The genomic structure of any gene should be taken into consideration when designing a mutation screening strategy. PMID- 17277738 TI - FOXL2 mutations in Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome. AB - PURPOSE: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant disorder where eyelid malformation associated with (type I) or without (type II) premature ovarian failure (POF). It is ascribed to mutations in the forkhead transcriptional factor2 (FOXL2) gene. The purpose of this study is to identify mutations in FOXL2 of Chinese patients with BPES. METHODS: Genomic DNA was prepared from leucocytes of peripheral venous blood. The coding regions and nearby intron sequences of FOXL2 were analyzed by cycle and cloning sequencing. RESULTS: Four mutations in FOXL2 were identified in six families, including c.241T>C, c.650C>G, c.804dupC, and c.672_701dup. Of the four, the c.241T>C and c.650C>G were novel and would result in missense changes of the encoded proteins, i.e., p.Tyr81His and p.Ser217Cys, respectively. The c.672_701dup (p.Ala224_Ala234dup) was detected in three families, indicating a mutation hotspot. The c.804dupC (p.Gly269ArgfsX265) mutation was found in one family. CONCLUSIONS: Our results expand the spectrum of FOXL2 mutations and confirm the mutation hotspot in FOXL2. PMID- 17277739 TI - Retina regeneration in the chick embryo is not induced by spontaneous Mitf downregulation but requires FGF/FGFR/MEK/Erk dependent upregulation of Pax6. AB - PURPOSE: To elucidate the early cellular events that take place during induction of retina regeneration in the embryonic chick, focusing on the relationship between fibroblast growth factor (FGF) signaling and the regulation of Pax6 and Mitf. METHODS: The retina of embryonic day 4 (E4) chicks was removed and a heparin coated bead soaked in fibroblast growth factor 2 (FGF2) was placed into the optic cup. The pharmacological inhibitor PD173074 was used to inhibit FGF receptors, PD98059 was used to inhibit MAP kinase-kinase/extracellular signal regulated kinase (MEK/Erk) signaling. Retroviral constructs for paired box 6 (Pax6), MEK, and microphthalmia (Mitf) were also used in overexpression studies. Immunohistochemistry was used to examine pErk, Pax6, Mitf, and melanosomal matrix protein 115 (MMP115) immunoreactivity and bromodeoxyuridine (BrdU) incorporation at different time points after removing the retina. RESULTS: The embryonic chick has the ability to regenerate a new retina by the process of transdifferentiation of the retinal pigment epithelium (RPE). We observed that during the induction of transdifferentiation, downregulation of Mitf was not sufficient to induce transdifferentiation at E4 and that FGF2 was required to drive Pax6 protein expression and cell proliferation, both of which are necessary for transdifferentiation. Furthermore, we show that FGF2 works through the FGFR/MEK/Erk signaling cascade to increase Pax6 expression and proliferation. Ectopic Mitf expression was able to inhibit transdifferentiation by acting downstream of FGFR/MEK/Erk signaling, likely by inhibiting the increase in Pax6 protein in the RPE. CONCLUSIONS: FGF2 stimulates Pax6 expression during induction of transdifferentiation of the RPE through FGFR/MEK/Erk signaling cascade. This Pax6 expression is accompanied by an increase in BrdU incorporation. In addition, we show that Mitf is spontaneously downregulated after removal of the retina even in the absence of FGF2. This Mitf downregulation is not accompanied by Pax6 upregulation, demonstrating that FGF2 stimulated Pax6 upregulation is required for transdifferentiation of the RPE. Furthermore, we show that ectopic Mitf expression is able to protect the RPE from FGF2 induced transdifferentiation by inhibiting Pax6 upregulation. PMID- 17277740 TI - Vitreous induces heme oxygenase-1 expression mediated by transforming growth factor-beta and reactive oxygen species generation in human retinal pigment epithelial cells. AB - PURPOSE: When human retinal pigment epithelial (RPE) cells come in contact with vitreous, they undergo changes in gene expression that include inflammatory and anti-oxidant responses. The effects of vitreous on expression of heme oxygenase-1 (HO-1), metallothionein (MT) -1a and -2a, and c-fos were investigated. Activator protein-1 (AP-1) binding sites are located in the promoter region of HO-1 and MT genes and the effects of vitreous on c-fos activity were investigated. METHODS: Low passage cultures of human RPE cells were grown in the presence or absence of vitreous or transforming growth factor-beta (TGF-beta). The expression of HO-1 and MTs was measured by real time PCR and, in the case of HO-1, by immunoblotting and immunofluorescence microscopy. Specific inhibitors were used to investigate possible signaling pathways. The effect of vitreous on activation of AP-1 transcription factor was determined by immunoblotting, electrophoretic mobility shift assays, or immunofluorescence microscopy. RESULTS: Incubation of RPE cells with vitreous resulted in increased expression of HO-1, MT-1a and MT-2a. TGF-beta caused an increase in HO-1 expression, although not to the extent mediated by vitreous, but had little effect on MT expression. Addition of inhibitors of TGF beta signaling (SB431542 or TGF-beta-neutralizing antibodies) decreased the vitreous induction of HO-1. Several reactive oxygen species (ROS) quenchers inhibited the TGF-beta-induced or vitreous-induced elevation of HO-1 mRNA but had no effect on vitreous-mediated induction of MT expression. Inhibitors of the mitogen-activated protein kinase (p38MAPK; SB203580) and Jun N-terminal kinase (JNK; SP600125) pathways inhibited vitreous-induction of HO-1. C-fos, a component of AP-1 transcription factor complexes, exhibited increased expression and activation in the presence of vitreous. CONCLUSIONS: TGF-beta, a known component of vitreous, can account for some but not all of the regulation of the anti oxidant, anti-inflammatory HO-1 gene in human RPE cells, but it does not participate in the vitreous-mediated upregulation of MTs. Both vitreous and TGF beta signals increased HO-1 expression via ROS but the latter were not involved in vitreous-mediated MT expression. Increased p38, JNK, and c-fos activation may be implicated in vitreous modulation of HO-1. PMID- 17277741 TI - Quantitative genetics of age-related retinal degeneration: a second F1 intercross between the A/J and C57BL/6 strains. AB - PURPOSE: Previously, several quantitative trait loci (QTL) that influence age related retinal degeneration (ageRD) were demonstrated in a cross between the C57BL/6J-c(2J) and BALB/cByJ strains (B x C). In this study, as a complementary approach to ongoing recombinant progeny testing for the purpose of identifying candidate quantitative trait genes (QTG), a second test cross using the A/J and the pigmented C57BL/6J strains (A x B) was carried out. The albino A/J strain was selected because it had the most amount of ageRD among several inbred strains tested, and the pigmented C57BL/6J strain was selected because along with its coisogenic counterpart C57BL/6J-c(2J) it had the least amount of ageRD. Thus, the effect of pigment on ageRD could be tested at the same time that the C57BL/6 genetic background was kept in common between the crosses from the two studies for the purpose of comparison. METHODS: A non-reciprocal F1 intercross between the A/J and C57BL/6J strains produced 170 F2 progeny. At 8 months of age after being maintained in relatively dim light, F2 mice, control mice and mice of other strains were evaluated for retinal degeneration by measurement of the thickness of the outer nuclear layer of the retina. The F2 mice were genotyped with dinucleotide repeat markers spanning the genome. Correlation of genotype with phenotype was made with Map Manager QTX software. RESULTS: Comparison of several strains of mice including the pigmented strains 129S1/SvImJ and C57BL/6J and the albino strains A/J, NZW/LacJ, BALB/cByJ and C57BL/6J-c(2J), showed significant differences in ageRD. The greatest difference was between the albino A/J strain and the pigmented C57BL/6J strain. However, there was no significant difference between the pigmented C57BL/6J and its albino coisogenic counterpart C57BL/6J c(2J). Neither was there significant difference between the pigmented and albino F2 mice from the A x B cross. On the other hand, F2 males had a small but significantly lower amount of ageRD than females. Several QTL were identified in the A x B cross but surprisingly none of the 3 major QTL present in the original B x C cross (Chrs 6, 10, and 16) was present. There were minor QTL on proximal Chr 12 and proximal Chr 14 in common between the two crosses, and the proximal Chr 12 QTL was present in a previous light damage study involving the B and C strains. At least one sex-limited QTL was present on the X chromosome with a peak in a different location from that of a sex-limited QTL in the previous B x C study. In addition, the protective X allele was from the BALB/cByJ strain in the B x C cross and from C57BL/6J in the A x B cross. In both crosses, the C57BL/6J X chromosome allele was recessive. CONCLUSIONS: Significant differences were observed in ageRD among several inbred strains of mice maintained in relatively dim light. AgeRD was not influenced by pigment but was influenced by gender, albeit to a small degree. The presence of the same QTL in one light-induced and two ageRD studies suggests at least partial commonality in retinal degeneration pathways of different primary cause. However, the three main QTL present in the B x C cross were absent from the A x B cross. This suggests that the genetic determinants responsible for the greater sensitivity to ageRD of BALB/cByJ and A/J relative to C57BL/6J are not the same. This is supported by the presence of sex-limited X-chromosome QTL in the two crosses in which the C57BL/6J allele is protective relative to the A allele and sensitive relative to the C allele. The findings in the two studies of differing allelic relationships of QTG, and differing QTL aid the identification of candidate genes mapping to critical QTL. Identifying natural modifying genes that influence retinal degeneration resulting from any causal pathway, especially those QTG that are protective, will open avenues of study that may lead to broad based therapies for people suffering retinal degenerative diseases. PMID- 17277744 TI - Scleral granuloma associated with presumed diffuse immune lymphocytosis syndrome. PMID- 17277745 TI - Corneal striae in thyroid eye disease. PMID- 17277742 TI - Identification and expression of Hop, an atypical homeobox gene expressed late in lens fiber cell terminal differentiation. AB - PURPOSE: To identify transcripts expressed late in lens fiber cell maturation that might regulate fiber cell fusion, organelle degradation, or other events associated with the maturation of lens fiber cells. METHODS: cDNA libraries were prepared from microdissected regions of chicken embryo lenses using a PCR-based method. Subtractive hybridization was used to identify transcripts expressed exclusively in fiber cells that had detached from the lens capsule. Database searches and PCR amplification with degenerate primers were used to identify human, mouse, rat, rabbit, and bovine orthologs of one such sequence and to confirm its expression in the lenses of these animals. The ability of in vitro transcribed and translated protein to bind DNA was assessed by mobility shift assays. The locus encoding this transcript and an area about 6 kb upstream of the translation start site were sequenced. The microscopic morphology of lenses from mice in which the locus encoding this protein had been disrupted by the insertion of a nuclear-targeted bacterial lacZ sequence were analyzed. Gene expression was analyzed by PCR, in situ hybridization, and by staining for beta-galactosidase activity in lenses expressing lacZ in place of the coding sequence. Knockout lenses expressing green fluorescent protein in a mosaic pattern were sectioned in the equatorial plane and viewed with a confocal microscope to assess the presence of cell-cell fusions during fiber cell maturation. RESULTS: Subtractive hybridization identified transcripts encoding Hop, a short, atypical homeodomain containing protein that had previously been shown to be an important regulator of gene expression in the heart and lung. Chicken Hop did not bind to known homeodomain-binding sequences in DNA. In chicken embryos, Hop transcripts were first detected at E6. At all stages analyzed, Hop mRNA was only detected in cells that had detached from the lens capsule. Mice in which the Hop coding sequence was replaced with nuclear-targeted beta-galactosidase showed that Hop was expressed in the mouse lens in a similar pattern to the chicken lens. Characterization of lenses from mice lacking Hop revealed no morphological phenotype and no apparent defects in the degradation of nuclei or fiber cell fusion during fiber cell maturation. CONCLUSIONS: The expression pattern of Hop provides the first evidence that new transcription is initiated in lens fiber cells after they detach from the capsule. Hop may be the first of a class of genes with this pattern of expression. Although lens abnormalities have yet to be identified in mice lacking Hop, the genomic sequences that regulate Hop expression in the lens may be useful for expressing exogenous transcripts selectively in fiber cells just before they fuse with their neighbors and degrade their organelles. PMID- 17277743 TI - Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A188 from the alphaA-crystallin promoter. AB - PURPOSE: During growth of the embryonic eye, dose- and site-specific expression of heparin-binding growth factors is critical for the formation of an appropriate vascular supply. Overexpression of vascular endothelial growth factor-A(188) (VEGF-A(188)), a strongly heparin-binding, endothelial-specific mitogen, leads to severe disturbance of vascular and overall ocular morphology. This study aimed to evaluate the effects of VEGF-A(188) overexpression on growth of ocular tissue components. METHODS: Stereological and immunohistochemical methods were employed to identify the vascular profiles, ocular tissue proportions, and cell types in VEGF-A(188) transgenic mice and compare them with wild-type mice. RESULTS: In VEGF-A(188) transgenic mice, both lens tissue and total ocular volume were reduced, whereas cross-sectional areas of hyaloid blood vessels, retina, iris, and optic stalk tissues were significantly increased compared to wild-type mice. Endothelial and pericyte cell numbers in the hyaloid vasculature of transgenic mice were increased three fold, with pericytes assuming their characteristic extraluminal position. CONCLUSIONS: Overexpression of VEGF-A(188) in the murine lens results in microphthalmia, in addition to hypertrophy and persistence of the hyaloid vasculature. This is similar to the human disorder persistent hyperplastic primary vitreous (PHPV). The murine model is a useful, experimental paradigm for investigation of this condition. PMID- 17277746 TI - Intraocular lens migration following posterior capsulotomy in retinitis pigmentosa. PMID- 17277747 TI - Acceptance of cataract surgery in a cohort of Tanzanians with operable cataract. AB - BACKGROUND: In spite of recent increases in the number of surgeries carried out within some hospitals and programmes in sub-Saharan Africa, there are indications that the acceptance of cataract surgery remains quite low. METHODS: We conducted a population-based prospective (cohort) study of cataract patients from 12 villages in Hai district of Kilimanjaro region, Tanzania. Those identified with operable cataract were informed of the regular community programmes (within 5 km) in place providing transportation and high-quality surgery. At years 1 and 2 after the survey, we traced the patients to determine uptake of cataract surgery. RESULTS: Among patients eligible for surgery (128), 31 could not be followed up after 1 year due to deaths, moving, and refusal. Among the remaining patients, 18 accepted surgery in the first year and four accepted in the second year. Among these 22 patients, only five were blind or with severe visual impairment. The most elderly were those least likely to accept surgery. DISCUSSION: Even with bridging strategies in place to make cataract surgery accessible and affordable, the uptake of cataract surgery remains low. Strategies aimed to identifying and referring all patients recognizing vision loss as a personal disability rather than using predefined vision cutoffs will likely be most successful in reducing the burden of vision loss due to cataract. PMID- 17277748 TI - CRMP-5-IgG in patient with paraneoplastic optic neuritis with lung adenocarcinoma. PMID- 17277749 TI - Acute leber hereditary optic neuropathy in a 73-year-old man. PMID- 17277750 TI - Recovery of stereoacuity 27 years after trauma: an unusual case. PMID- 17277751 TI - Prevention and control of proliferative vitreoretinopathy: primary retinal detachment surgery using silicone oil as a planned two-stage procedure in high risk cases. AB - AIMS: For rhegmatogenous retinal detachment, reattachment with a single procedure is associated with better visual outcomes. In the past, silicone oil has been used mostly as a last resort following failed primary surgery. This study evaluates a novel approach to patients at high risk of primary failure, using silicone tamponade as the primary stage of a planned two-stage procedure. METHODS: We report a series of 140 eyes that underwent primary surgery for rhegmatogenous retinal detachment. Patients at higher risk of surgical failure (eg giant retinal tear, inability to posture, poor view, uncertainty of location of primary break, primary proliferative vitreoretinopathy (PVR), multiple tears with rolled posterior edges, retinoschisis/detachment, staphyloma with macular hole) were managed by a planned staged procedure using primary silicone oil tamponade. This was followed by silicone removal at a later date. RESULTS: Fifty four eyes underwent scleral buckling alone, with primary success in 52/54 (96%). Fifty-three eyes underwent vitrectomy and gas, achieving primary success in 50/53 (94%). Thirty-three eyes were classified high risk and managed with primary silicone. Silicone was safely removed in 22/25. In eight eyes, silicone was retained without attempt at removal. In total, primary retinal reattachment was achieved in 128 of 140 eyes (91.4%). Of these, 124 (97%) did not require long term tamponade. Only four eyes (2.9%) developed PVR. DISCUSSION: A planned two stage approach to highrisk cases of retinal detachment using primary silicone oil tamponade followed by silicone removal can achieve a high primary reattachment rate with less than 3% incidence of PVR. PMID- 17277752 TI - A retrospective analysis to determine the effect of independent treatment centres on the case mix for microsurgical training. AB - AIM: To determine the effect of Independent Sector Treatment Centres (ISTC) on microsurgical training. METHODS: A novel scoring protocol for stratification of cases suitable for microsurgical training was devised. This scoring protocol was applied to all patients who underwent cataract surgery on a single consultant dedicated training list between September and November 2004. These patients are representative of patients remaining on the waiting list after ISTC selection, that is, the residual case mix. Patients who underwent cataract surgery on the same consultant list in the same period in 2003 were also analysed when there was no ISTC or other waiting list initiative in operation. RESULTS: Data was available for 129 patients. Seventy three patients underwent cataract surgery between September and November 2003 and 56 patients underwent cataract surgery in the same period in 2004. Using the devised scoring protocol, the mean score in the 2003 group was 1.08 +/-1.75 (range, 0.0-10.5) and for the 2004 group the mean score was 2.31 +/-2.65 (range, 0.0-4.5). A Mann-Whitney test showed that there was a statistically significant difference between the scores in the two groups (P=0.0009). With Independent Sector Treatment Centre implementation the percentage of cases suitable only for consultants increased fourfold. CONCLUSION: The decrease in suitable cases for training as shown in this study is likely to have serious consequences on microsurgical training in the UK. We recommend that the results of this study are considered in any current or future plans for ISTC continuation and expansion. PMID- 17277754 TI - Minimally invasive surgery-endoscopic retinal detachment repair in patients with media opacities. AB - PURPOSE: Evaluate the use of an ophthalmic endoscope in patients with a retinal detachment and anterior media opacity. MATERIALS AND METHODS: A retrospective interventional case series. Search of a comprehensive database of retinal detachment patients with pre-operatively impaired anterior segments such that lens extraction, a keratoprosthesis, or extensive anterior segment manipulation was required for adequate repair. Pars plana vitrectomy was carried out with an endoscope without manipulation of the anterior segment. Characteristics of the detachment were recorded, as were complications/subsequent surgeries, pre operative, 3-month post-operative, and final follow-up visual acuities. RESULTS: Before surgery, five patients had a gas-induced cataract after a failed pneumatic retinopexy; one patient had a Reis-Buckler's dystrophy and corneal ulcer; three patients had synechiae around iris-fixed lenses. One patient had proliferative vitreoretinopathy. The median pre-operative vision was hand motion (20/30 to light perception). The median final visual acuity was 20/30 (20/20-20/200). Two patients required a subsequent lens extraction, one patient had a recurrent detachment. CONCLUSION: In appropriate retinal detachment patients, endoscopy can be safe and effective, while limiting the scope of the surgical intervention. PMID- 17277755 TI - Muckle-Wells syndrome: another cause of acute anterior uveitis. PMID- 17277753 TI - Expression of immature and mature retinal cell markers in retinoblastoma. AB - AIM: To clarify the expression of immature and mature retinal cell makers in retinoblastoma cells and to give insights into the cell origin of the retinoblastoma. MATERIALS AND METHODS: Five samples from five eyes diagnosed with retinoblastomas were analysed by a standard immunohistochemistry using antibodies against Nestin and the hairy and enhancer of split mammalian homologue-1 (HES-1), both as markers for undifferentiated cells, and against Chx10, as a marker for both undifferentiated retinal cells and mature bipolar cells. Photoreceptor specific nuclear receptor (PNR) was used as a postmitotic rod photoreceptor cell specific marker, glial fibrillary acidic protein (GFAP) as a mature glia cell marker, and microtubule-associated protein (MAP) 2 as a mature neuronal cell marker. RESULTS: Nestin was detected in what were possibly Muller cells, but not in the tumour stroma. HES-1 was not detected in the retinoblastoma tissue. Chx10 was detected in one of the five samples. In this one sample, Chx10 expression was confined in a minor portion of the retinoblastoma cells. PNR was not detected in the retinoblastoma tissue. Expression of GFAP was detected only in the stromal cells of the tumour, which presumably represents reactive stromal astrocytes. In contrast, in all the samples, MAP2 was expressed in most of the retinoblastoma cells. CONCLUSIONS: The results of the current study support that retinoblastomas are derived from mature neural cells but do not originate from tumour stem cell(s). PMID- 17277756 TI - Ethnic differences in refraction and ocular biometry in a population-based sample of 11-15-year-old Australian children. AB - PURPOSE: To examine the prevalence of refractive error and distribution of ocular biometric parameters among major ethnic groups in a population-based sample of 11 15-year-old Australian children. METHODS: The Sydney Myopia Study examined 2353 students (75.3% response) from a random cluster-sample of 21 secondary schools across Sydney. Examinations included cycloplegic autorefraction, and measures of corneal radius of curvature, anterior chamber depth, and axial length. RESULTS: Participants mean age was 12.7 years (range 11.1-14.4); 49.4% were female. Overall, 60.0% of children had European Caucasian ethnicity, 15.0% East Asian, 7.1% Middle Eastern, and 5.5% South Asian. The most frequent refractive error was mild hyperopia (59.4%, 95% confidence interval (CI), 53.2-65.6), defined as spherical equivalent (SE) +0.50 to +1.99 D. Myopia (SE-0.50 D or less) was found in 11.9%, 95% (CI 6.6-17.2), and moderate hyperopia (SE> or =+2.00 D) in 3.5%, 95% (CI 2.8-4.1). Myopia prevalence was lower among European Caucasian children (4.6%, 95% CI 3.1-6.1) and Middle Eastern children (6.1%, 95% CI 1.3-11.0) than among East Asian (39.5%, 95%, CI 25.6-53.5) and South Asian (31.5%, 95%, CI 21.6 41.4) children. European Caucasian children had the most hyperopic mean SE (+0.82 D) and shortest mean axial length (23.23 mm). East Asian children had the most myopic mean SE (-0.69 D) and greatest mean axial length (23.86 mm). CONCLUSION: The overall myopia prevalence in this sample was lower than in recent similar aged European Caucasian population samples. East Asian children in our sample had both a higher prevalence of myopia and longer mean axial length. PMID- 17277757 TI - Aspergillus fumigatus keratitis after laser in situ keratomileusis: a case report and review of post-LASIK fungal keratitis. PMID- 17277758 TI - Acute endophthalmitis following intravitreal bevacizumab (Avastin) injection. AB - PURPOSE: To report two cases of acute endophthalmitis following intravitreal bevacizumab injection. METHODS: Two patients with exudative age-related macular degeneration were treated sequentially with an intravitreal injection of bevacizumab and developed signs of severe but painless infectious endophthalmitis 2 days later. Vitreous samples were obtained, followed by the injection of vancomycin 1 mg/0.1 ml and ceftazidime 2.25 mg/0.1 ml. Pulsed-field gel electrophoresis (PFGE) was used to determine whether the isolated microorganisms were the same. RESULTS: Coagulase-negative staphylococci were identified and isolated from the vitreous specimen of both patients. PFGE revealed different patterns of banding, excluding that interpatient contamination occured. CONCLUSIONS: Infectious endophthalmitis is a potential complication of intravitreal bevacizumab injection. PMID- 17277759 TI - Increased risk of concurrent primary malignancies in patients diagnosed with a primary malignant epithelial ovarian tumor. AB - Ovarian cancer and second malignant neoplasms are found to occur rather frequently in the same patient. From a clinical perspective, it is important to have quantitative information on concurrent malignancies in the same year of diagnosis of the epithelial ovarian cancer. In this population-based study, we used data from the Netherlands Nationwide Network for Registry of histo- and cytopathology (PALGA) and the Netherlands Cancer Registry (NCR). Data of the ovarian cancer as well as data on previous or later cancers were obtained. Age specific cancer rates from the NCR were used to calculate expected numbers of cancer. Between 1987 and 1993, histopathology reports were identified of 4577 patients with primary epithelial malignant or primary borderline malignant ovarian cancers and its longitudinal data. As the database may lack detailed information on histopathology, a recent sample of 789 patients diagnosed with ovarian cancer in 1996-2003 was comprehensively studied as well. In the eventual data analysis of 5366 patients, 244 cases (4.5%) of concurrent primary malignancy were reported in the same year that the malignant epithelial ovarian tumor had been diagnosed against 51 expected. The observed vs expected ratio was 4.8 and the 95% confidence interval (CI) (4.3-5.5). For cancer of the uterus/endometrium the observed vs expected ratio was 62.3 (95% CI 52.5-73.5). For skin, breast, colorectal, urinary bladder, renal and cervical cancer the ratio was also larger than unity. The elevated risk of concurrent cancer may lead to clinical screening protocols. The findings on endometrial cancer may prompt research on common etiologies and biomarkers. PMID- 17277760 TI - Human leukocyte antigen G expression: as a significant prognostic indicator for patients with colorectal cancer. AB - Aberrant expression of human leukocyte antigen G (HLA-G) has been proposed to be involved in tumor escape mechanisms. It has been also proposed that detection of HLA-G might service as a potential biomarker for diagnosis or prediction of the clinical outcomes in ovarian and breast cancers, carcinoma of the lung and endometrial cancer. The aim of this current study is to determine if HLA-G is expressed in colorectal carcinomas and if the expression is associated with clinicopathological and prognostic data. The expression of HLA-G was investigated immunohistochemically in 201 patients with colorectal carcinomas. The correlation between HLA-G status, clinicopathological factors and the overall survival rate was analyzed. In this prospectively study, HLA-G protein expression was observed in 64.6% (130/201) of the primary site colorectal carcinomas, but not in the normal colorectal tissues or benign adenomas. HLA-G expression in the tumors was significantly correlated with the depth of invasion, histological grade, host immune response, lymph nodal metastasis and clinical stages of the disease (P=0.001, 0.0001, 0.002, 0.001 and 0.031, respectively). Patients with HLA-G positive tumors had a significantly shorter survival time than those patients with tumors that were HLA-G negative (P=0.0001). As well, in multivariate analysis, HLA-G demonstrated an independent prognostic factor (P=0.021, relative risk 3.14; 95% confidence interval, 1.34-8.10). Therefore, it can be gathered that HLA-G might serve as an independent prognostic factor for colorectal cancer patients. PMID- 17277761 TI - D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30. AB - The distinction between seminoma and embryonal carcinoma based on morphology alone can sometimes be problematic, requiring the use of immunohistochemistry to facilitate diagnosis. D2-40 is a monoclonal antibody that reacts with an oncofetal antigen expressed by fetal germ cells and testicular germ cell tumors. The diagnostic value of D2-40 immunohistochemistry in distinguishing seminoma from embryonal carcinoma has not been determined. D2-40 immunoreactivity was evaluated in a series of testicular germ cell tumors and compared with that of KIT (CD117) and CD30, to assess the relative utility of this marker in discriminating between seminoma and embryonal carcinoma. Forty testicular germ cell neoplasms were examined, which included 19 seminomas, three embryonal carcinomas, three teratomas, one yolk sac tumor, and 14 mixed germ cell tumors. The 14 cases of mixed germ cell tumors contained components of seminoma (n=7), embryonal carcinoma (n=11), teratoma (n=10), yolk sac tumor (n=2), and choriocarcinoma (n=1). All cases of pure seminoma and the seminomatous components of mixed germ cell tumors exhibited positive immunoreactivity for D2-40. Focal positivity for D2-40 was also observed in 29% of the embryonal carcinoma samples. D2-40 immunoreactivity in seminomas was characterized by diffuse membrane staining, whereas for embryonal carcinomas, staining was focal and distributed along the apical surfaces of the neoplastic cells. Immunohistochemical staining for KIT was observed in 92% of the seminoma samples and in none of the embryonal carcinomas. Conversely, CD30 expression was identified in 93% of the embryonal carcinoma samples and in none of the seminomas. Other germ cell components showed no immunoreactivity for D2-40, KIT, or CD30. KIT and CD30 are effective immunohistochemical markers in separating seminoma from embryonal carcinoma. Although a highly sensitive marker for seminomas, D2-40 positivity was also observed in a subset of embryonal carcinomas, thus limiting the utility of this antibody for discriminating between these two malignancies. PMID- 17277762 TI - Colonic neuropathological aspects in patients with intractable constipation due to obstructed defecation. AB - One of the most frequent subtypes of constipation is represented by obstructed defecation, and it has recently been reported that these patients may have colonic motor abnormalities in addition to alterations of the anorectal area. However, it is unknown whether these patients display abnormalities of the enteric nervous system, as reported in other groups of constipated subjects. For this reason, we evaluated the neuropathologic aspects of the enteric nervous system in a homogeneous group of patients with obstructed defecation. Colonic specimens from 11 patients (nine women, age range 39-66 years) undergoing surgery for symptoms refractory to any therapeutic measure, including biofeedback training, were obtained and examined by means of conventional histological methods and immunohistochemistry (NSE, S100, c-Kit, formamide-mAb, Bcl-2, CD34, alfa-actin). Analysis of the specimens showed that the enteric neurons were significantly decreased only in the submucosal plexus of patients (P<0.0001 vs controls), whereas the enteric glial cells of constipated patients were reduced in both the myenteric (P=0.018 vs controls) and the submucosal plexus (P=0.004 vs controls). No difference between patients and controls were found concerning c Kit and CD34 expression, and the number of apoptotic neurons. These findings support the concept that at least a subgroup of patients with obstructed defecation and severe, intractable symptoms display abnormalities of the enteric nervous system, mostly related to the enteric glial cells. These findings might explain some of the pathophysiological abnormalities, and help to better understand this condition. PMID- 17277763 TI - Exuberant type 2 pneumocyte hyperplasia associated with spontaneous pneumothorax: secondary reactive change mimicking adenocarcinoma. AB - A wide variety of pulmonary and pleural histological changes is recognized in the setting of spontaneous pneumothorax. In this study, we describe a previously unreported lesion that was encountered in four males, 24-41 years of age. In addition to reactive eosinophilic pleuritis, subpleural emphysematous blebs, prominent eosinophilic exudate and lung atelectasis, the histology comprised exuberant type 2 pneumocyte hyperplasia, which was atypical enough to consider a diagnosis of adenocarcinoma in all four cases. Lung atelectasis and localized acute lung injury are factors likely responsible for this unusual histology, and along with the clinical history are important in recognizing the benign nature of this lesion. Awareness of this severe pneumocyte reaction in the setting of pneumothorax can help to prevent misdiagnosis as malignancy. PMID- 17277765 TI - ALK-positive diffuse large B-cell lymphoma: report of four cases and review of the literature. AB - We report detailed clinical and pathologic features of four cases of anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL), a rare entity with only 29 currently reported cases. This study is the third largest of all reported series. Biopsies from four adult patients aged 41, 49, 53, and 71 years (three lymph nodes and one nasopharyngeal mass) exhibited immunoblastic/plasmablastic morphology. By immunohistochemistry and/or flow cytometry, they expressed cytoplasmic ALK-1, CD138, VS38 (3/3), monoclonal cytoplasmic light chain, CD45, EMA, CD4, and CD57 (2/3), and were negative for CD3, CD30, CD56, and TIA-1. Two showed variable CD79a expression, and one had rare CD20(+) cells. Two of three cases exhibited rare CD43(+) reactivity. One case showed scattered cytokeratin(+) cells, which could possibly lead to a misdiagnosis of carcinoma. After CHOP and radiotherapy, two stage I patients were free of disease at 58 and 36 months, whereas a stage IV patient was dead of disease at 22 months. PMID- 17277764 TI - Reelin expression in human prostate cancer: a marker of tumor aggressiveness based on correlation with grade. AB - Reelin is a glycoprotein that plays a critical role in the regulation of neuronal migration during brain development and, since reelin has a role in the control of cell migration, it might represents an important factor in cancer pathology. In this study, 66 surgical specimens of prostate cancer were analyzed for reelin expression by immunohistochemical method. The reelin expression was correlated with Gleason score and individual Gleason patterns. Reelin expression was found in 39% prostate cancers. Stromal tissues, normal epithelial cells and prostate intraepithelial neoplasia (PIN) of any grade around and distant from cancer were always negative for reelin. Reelin was found in malignant prostatic epithelial glands of 50% cases Gleason score 10, 52% Gleason score 9, 56% Gleason score 8, 18% Gleason score 7, while no sample of prostate cancers with Gleason score 6 showed reelin expression (P=0,005). As reelin staining is frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns. While Gleason 3 pattern did not show reelin immunoreactivity, reelin expression was found in 35% Gleason 4 patterns and 45% Gleason 5 patterns (P<0.001). Our results demonstrated for the first time that reelin is expressed in prostate cancer and not in benign prostate tissue and its expression occurs in higher Gleason score and correlates significantly with increasing of single Gleason patterns. This suggests reelin may behave as a specific histological marker and may represent a useful biomarker to predict aggressive phenotypic behavior of prostatic cancer cells. PMID- 17277766 TI - Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma. AB - Breast carcinoma with a high histologic grade is highly invasive and metastatic. One reason for its irregular morphology is the formation of excessive protrusions due to assemblages of branched actin filament networks. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein2 (WAVE2), a member of the WASP protein family. In this study, the localization Arp2 and WAVE2 in breast carcinoma was investigated to clarify whether coexpression of the two proteins is associated with histologic grade or patient outcome. Immunohistochemical staining of Arp2 and WAVE2 was performed on mirror specimens of 197 breast carcinomas, and the association between coexpression of the two proteins and clinicopathologic factors was examined. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of Arp2 and WAVE2 coexpression in breast carcinoma. Coexpression of Arp2 and WAVE2 was detected in 64 (36%) of 179 invasive ductal carcinomas and in 2 (11%) of 18 ductal carcinomas in situ, but was not detected in any adjacent non-cancerous tissue. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with high histologic grade (P<0.0001), and cases with lymph node metastasis (P=0.0150). The patients whose cancer cells showed such coexpression had shorter disease-free (P=0.0002) and overall survival (P=0.0122) than patients whose cancer cells expressed only one or none of Arp2 and WAVE2. Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent factor for both tumor recurrence (P=0.0308) and death (P=0.0455). These results indicate that coexpression of Arp2 and WAVE2 is a significant prognostic factor that is closely associated with aggressive morphology of invasive ductal carcinoma of the breast. PMID- 17277767 TI - Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer. AB - Mammalian Sterile20-like kinase 1 (Mst1) is a member of the yeast Ste20-related kinase family known to be involved in the process of apoptosis initiated by a variety of stimuli. The aim of this study was to determine the prognostic significance of Mst1 expression in colorectal cancer. A series of 1197 mismatch repair-proficient colorectal cancers retrieved from a tissue microarray were randomized into two study groups. On the first group (n=599) receiver operating characteristic curves were used to determine the most clinically useful cutoffs to describe Mst1 expression with respect to T stage, N stage, tumor grade, vascular invasion and overall survival. The association of Mst1 expression and each outcome was immunohistochemically evaluated on the second study group (n=598) as well as on a third study group comprising 141 mismatch-repair deficient colorectal cancers. A univariate analysis in the second study group showed that loss of cytoplasmic Mst1 was associated with higher T stage (P=0.001), higher N stage (P=0.029), vascular invasion (P=0.017) and overall survival (P=0.014). Nuclear Mst1 expression was not significantly associated with N stage, T stage or vascular invasion but was associated with tumor grade. In mismatch-repair-deficient colorectal cancers, loss of cytoplasmic Mst1 was associated with higher N stage (P=0.019) and shortened survival (P=0.0001). In a multivariate analysis, loss of cytoplasmic Mst1 was an independent adverse prognostic factor in this group of patients. Methylation analysis on 32 cases showed that the loss of cytoplasmic Mst1 expression is not likely due to promoter methylation. In summary, loss of cytoplasmic Mst1 expression is a marker of tumor progression in mismatch-repair-proficient as well as mismatch-repair-deficient colorectal cancers. These results are suggestive of a tumor suppressor role for Mst1 in human colorectal cancer. PMID- 17277768 TI - Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma. AB - The hallmark of chromophobe renal cell carcinoma is multiple chromosomal losses from among chromosomes 1, 2, 6, 10 and 17. Chromophobe renal cell carcinoma with distant metastases or sarcomatoid transformation are uncommon and little is known about their chromosomal abnormalities. We collected six sarcomatoid chromophobe renal cell carcinomas and three primary chromophobe renal cell carcinomas with distant metastases. A cytogenetic analysis by fluorescent in situ hybridization on paraffin-embedded tissue was performed using centromeric probes for chromosomes 1, 2, 6, 10 and 17. We found more than one signal in four of six (66%) sarcomatoid chromophobe renal cell carcinomas, in both sarcomatoid and adjacent epithelial components. Both primary chromophobe renal cell carcinomas and matched metastases showed single signals for all chromosomes studied in two cases and no abnormalities in the remaining case. We concluded that: (1) both epithelial and sarcomatoid components of sarcomatoid chromophobe renal cell carcinoma show different genetic abnormalities from those characteristic of chromophobe renal cell carcinoma; (2) sarcomatoid chromophobe renal cell carcinomas frequently have multiple gains (polysomy) of chromosomes 1, 2, 6, 10 and 17; (3) distant metastases show the same genetic patterns, usually chromosomal losses (monosomy), found in the primary tumors. PMID- 17277769 TI - eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. AB - Regulation of protein synthesis is critical for cell growth and maintenance. Ageing in many organisms, including humans, is accompanied by marked alterations in both general and specific protein synthesis. Whether these alterations are simply a corollary of the ageing process or have a causative role in senescent decline remains unclear. An array of protein factors facilitates the tight control of messenger RNA translation initiation. The eukaryotic initiation factor 4E (eIF4E), which binds the 7-monomethyl guanosine cap at the 5' end of all nuclear mRNAs, is a principal regulator of protein synthesis. Here we show that loss of a specific eIF4E isoform (IFE-2) that functions in somatic tissues reduces global protein synthesis, protects from oxidative stress and extends lifespan in Caenorhabditis elegans. Lifespan extension is independent of the forkhead transcription factor DAF-16, which mediates the effects of the insulin like signalling pathway on ageing. Furthermore, IFE-2 deficiency further extends the lifespan of long-lived age and daf nematode mutants. Similarly, lack of IFE-2 enhances the long-lived phenotype of clk and dietary-restricted eat mutant animals. Knockdown of target of rapamycin (TOR), a phosphatidylinositol kinase related kinase that controls protein synthesis in response to nutrient cues, further increases the longevity of ife-2 mutants. Thus, signalling via eIF4E in the soma is a newly discovered pathway influencing ageing in C. elegans. PMID- 17277770 TI - The Ets transcription factor GABP is required for cell-cycle progression. AB - The transition from cellular quiescence (G0) into S phase is regulated by the mitogenic-activation of D-type cyclins and cyclin-dependent kinases (Cdks), the sequestration of the Cdk inhibitors (CDKIs), p21 and p27, and the hyperphosphorylation of Rb with release of E2F transcription factors. However, fibroblasts that lack all D-type cyclins can still undergo serum-induced proliferation and key E2F targets are expressed at stable levels despite cyclical Rb-E2F activity. Here, we show that serum induces expression of the Ets transcription factor, Gabpalpha, and that its ectopic expression induces quiescent cells to re-enter the cell cycle. Genetic disruption of Gabpalpha prevents entry into S phase, and selectively reduces expression of genes that are required for DNA synthesis and degradation of CDKIs, yet does not alter expression of D-type cyclins, Cdks, Rb or E2Fs. Thus, GABP is necessary and sufficient for re-entry into the cell cycle and it regulates a pathway that is distinct from that of D-type cyclins and CDKs. PMID- 17277771 TI - Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. AB - Insulin stimulates protein synthesis and cell growth by activation of the protein kinases Akt (also known as protein kinase B, PKB) and mammalian target of rapamycin (mTOR). It was reported that Akt activates mTOR by phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2). However, in recent studies the physiological requirement of Akt phosphorylation of TSC2 for mTOR activation has been questioned. Here, we identify PRAS40 (proline-rich Akt/PKB substrate 40 kDa) as a novel mTOR binding partner that mediates Akt signals to mTOR. PRAS40 binds the mTOR kinase domain and its interaction with mTOR is induced under conditions that inhibit mTOR signalling, such as nutrient or serum deprivation or mitochondrial metabolic inhibition. Binding of PRAS40 inhibits mTOR activity and suppresses constitutive activation of mTOR in cells lacking TSC2. PRAS40 silencing inactivates insulin-receptor substrate-1 (IRS-1) and Akt, and uncouples the response of mTOR to Akt signals. Furthermore, PRAS40 phosphorylation by Akt and association with 14-3-3, a cytosolic anchor protein, are crucial for insulin to stimulate mTOR. These findings identify PRAS40 as an important regulator of insulin sensitivity of the Akt-mTOR pathway and a potential target for the treatment of cancers, insulin resistance and hamartoma syndromes. PMID- 17277772 TI - Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. AB - Posttranslational modifications of histones, such as methylation, regulate chromatin structure and gene expression. Recently, lysine-specific demethylase 1 (LSD1), the first histone demethylase, was identified. LSD1 interacts with the androgen receptor and promotes androgen-dependent transcription of target genes by ligand-induced demethylation of mono- and dimethylated histone H3 at Lys 9 (H3K9) only. Here, we identify the Jumonji C (JMJC) domain-containing protein JMJD2C as the first histone tridemethylase regulating androgen receptor function. JMJD2C interacts with androgen receptor in vitro and in vivo. Assembly of ligand bound androgen receptor and JMJD2C on androgen receptor-target genes results in demethylation of trimethyl H3K9 and in stimulation of androgen receptor-dependent transcription. Conversely, knockdown of JMJD2C inhibits androgen-induced removal of trimethyl H3K9, transcriptional activation and tumour cell proliferation. Importantly, JMJD2C colocalizes with androgen receptor and LSD1 in normal prostate and in prostate carcinomas. JMJD2C and LSD1 interact and both demethylases cooperatively stimulate androgen receptor-dependent gene transcription. In addition, androgen receptor, JMJD2C and LSD1 assemble on chromatin to remove methyl groups from mono, di and trimethylated H3K9. Thus, our data suggest that specific gene regulation requires the assembly and coordinate action of demethylases with distinct substrate specificities. PMID- 17277773 TI - Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. AB - Throughout adulthood, new neurons are continuously added to the dentate gyrus, a hippocampal subregion that is important in spatial learning. Whether these adult generated granule cells become functionally integrated into memory networks is not known. We used immunohistochemical approaches to visualize the recruitment of new neurons into circuits supporting water maze memory in intact mice. We show that as new granule cells mature, they are increasingly likely to be incorporated into circuits supporting spatial memory. By the time the cells are 4 or more weeks of age, they are more likely than existing granule cells to be recruited into circuits supporting spatial memory. This preferential recruitment supports the idea that new neurons make a unique contribution to memory processing in the dentate gyrus. PMID- 17277774 TI - Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. AB - Dopamine (DA) D1 receptor (D1R) stimulation in prefrontal cortex (PFC) produces an 'inverted-U' dose-response, whereby either too little or too much D1R stimulation impairs spatial working memory. This response has been observed across species, including genetic linkages with human cognitive abilities, PFC activation states and DA synthesis. The cellular basis for the inverted U has long been sought, with in vitro intracellular recordings supporting a variety of potential mechanisms. The current study demonstrates that the D1R agonist inverted-U response can be observed in PFC neurons of behaving monkeys: low levels of D1R stimulation enhance spatial tuning by suppressing responses to nonpreferred directions, whereas high levels reduce delay-related firing for all directions, eroding tuning. These sculpting actions of D1R stimulation are mediated in monkeys and rats by cyclic AMP intracellular signaling. The evidence for an inverted U at the cellular level in behaving animals promises to bridge in vitro molecular analyses with human cognitive experience. PMID- 17277775 TI - Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. AB - A recessive form of severe osteogenesis imperfecta that is not caused by mutations in type I collagen has long been suspected. Mutations in human CRTAP (cartilage-associated protein) causing recessive bone disease have been reported. CRTAP forms a complex with cyclophilin B and prolyl 3-hydroxylase 1, which is encoded by LEPRE1 and hydroxylates one residue in type I collagen, alpha1(I)Pro986. We present the first five cases of a new recessive bone disorder resulting from null LEPRE1 alleles; its phenotype overlaps with lethal/severe osteogenesis imperfecta but has distinctive features. Furthermore, a mutant allele from West Africa, also found in African Americans, occurs in four of five cases. All proband LEPRE1 mutations led to premature termination codons and minimal mRNA and protein. Proband collagen had minimal 3-hydroxylation of alpha1(I)Pro986 but excess lysyl hydroxylation and glycosylation along the collagen helix. Proband collagen secretion was moderately delayed, but total collagen secretion was increased. Prolyl 3-hydroxylase 1 is therefore crucial for bone development and collagen helix formation. PMID- 17277776 TI - Differential translation efficiency of orthologous genes is involved in phenotypic divergence of yeast species. AB - A major challenge in comparative genomics is to understand how phenotypic differences between species are encoded in their genomes. Phenotypic divergence may result from differential transcription of orthologous genes, yet less is known about the involvement of differential translation regulation in species phenotypic divergence. In order to assess translation effects on divergence, we analyzed approximately 2,800 orthologous genes in nine yeast genomes. For each gene in each species, we predicted translation efficiency, using a measure of the adaptation of its codons to the organism's tRNA pool. Mining this data set, we found hundreds of genes and gene modules with correlated patterns of translational efficiency across the species. One signal encompassed entire modules that are either needed for oxidative respiration or fermentation and are efficiently translated in aerobic or anaerobic species, respectively. In addition, the efficiency of translation of the mRNA splicing machinery strongly correlates with the number of introns in the various genomes. Altogether, we found extensive selection on synonymous codon usage that modulates translation according to gene function and organism phenotype. We conclude that, like factors such as transcription regulation, translation efficiency affects and is affected by the process of species divergence. PMID- 17277777 TI - Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. AB - Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region. This approach accurately predicted the location and function of independently identified regulatory elements with high sensitivity and specificity and uncovered a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2). Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome. PMID- 17277778 TI - Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. AB - Autoimmune diseases are thought to result from imbalances in normal immune physiology and regulation. Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2). In order to test directly that an approximately twofold reduction in IL-2 underpins the Idd3 linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory effects of the naturally occurring susceptibility alleles of Il2. Reduced IL-2 production achieved by either genetic mechanism correlates with reduced function of CD4(+) CD25(+) regulatory T cells, which are critical for maintaining immune homeostasis. PMID- 17277779 TI - The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. AB - T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-kappaB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17 dependent signaling in autoimmune and inflammatory disease. PMID- 17277781 TI - Focused-ion-beam thinning of frozen-hydrated biological specimens for cryo electron microscopy. AB - Cryo-electron microscopy can provide high-resolution structural information about cells and organelles in the nearly native, frozen-hydrated state. Applicability, however, is limited by difficulties encountered in preparing suitably thin, vitreously frozen biological specimens. We demonstrate, by cryo-electron tomography of Escherichia coli cells, that a focused ion beam (FIB) can be used to thin whole frozen-hydrated cells in a convenient and essentially artifact-free way. PMID- 17277780 TI - Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin. AB - The autoimmune regulator Aire is expressed in a small proportion of medullary thymic epithelial cells (mTECs) and is crucial in the induction of central T cell tolerance. The origin and development of Aire(+) mTECs, however, are not well understood. Here we demonstrate that the tight-junction components claudin-3 and claudin-4 (Cld3,4) were 'preferentially' expressed in Aire(+) mTECs. In early ontogeny, Cld3,4(hi) TECs derived from the most apical layer of the stratified thymic anlage first expressed known mTEC markers such as UEA-1 ligand and MTS10. We provide evidence that such Cld3,4(hi) UEA-1(+) TECs represented the initial progenitors specified for Aire(+) mTECs, whose development crucially required NF kappaB-inducing kinase and the adaptor molecule TRAF6. Our results suggest that Aire(+) mTECs represent terminally differentiated cells in a unique lineage arising during thymic organogenesis. PMID- 17277782 TI - A retroviral strategy that efficiently creates chromosomal deletions in mammalian cells. AB - Chromosomal deletions, as a genetic tool for functional genomics, remain underexploited for vertebrate stem cells mostly because presently available methods are too labor-intensive. To address this, we developed and validated a set of complementary retroviruses that creates a wide range of nested chromosomal deletions. When applied to mouse embryonic stem cells (ESCs), this retrovirus based method yielded deletions ranging from 6 kb to 23 Mb (average 2.9 Mb), with an efficiency of 64% for drug-selected clones. Notably, several of the engineered ESC clones, mostly those with large deletions, showed major alteration in cell fate. In comparison to other methods that have also exploited retroviruses for chromosomal engineering, this modified strategy is more efficient and versatile because it bypasses the need for homologous recombination, and thus can be exploited for rapid and extensive functional screens in embryonic and adult stem cells. PMID- 17277783 TI - Ubc9 fusion-directed SUMOylation (UFDS): a method to analyze function of protein SUMOylation. AB - Although small ubiquitin-like modifier (SUMO) is conjugated to proteins involved in diverse cellular processes, the functional analysis of SUMOylated proteins is often hampered by low levels of specific SUMOylated proteins in the cell. Here we describe a SUMO-conjugating enzyme (Ubc9) fusion-directed SUMOylation (UFDS) system, which allows efficient and selective in vivo SUMOylation of proteins. Although SUMOylation of overexpressed p53 and STAT1 was difficult to detect in HEK293 cells, up to 40% of p53 and STAT1 were conjugated with endogenous SUMO when fused to Ubc9. We verified the specificity of UFDS using SUMOylation-site mutants and showed that the method is not dependent on SUMO ligases. Using UFDS we demonstrated that SUMOylation of STAT1 inhibits its phosphorylation at Tyr701 and discovered p53 multi-SUMOylation in vivo. We propose that UFDS will be useful for the analysis of function of SUMOylation in protein interactions, subcellular localization as well as enzymatic activity. PMID- 17277785 TI - Vitamin B6 conjugation to nuclear corepressor RIP140 and its role in gene regulation. AB - Pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, is an important cofactor in amino acid metabolism, and supplementary vitamin B6 has protective effects in many disorders. Other than serving as a cofactor, it can also modulate the activities of steroid hormone receptors and transcription factors. However, the molecular basis of this modulation is unclear. Here, we report that mouse nuclear receptor interacting protein 140 (RIP140) can be modified by PLP conjugation. We mapped the modification site to Lys613 by LC-ESI MS/MS analysis. This modification enhanced its transcriptional corepressive activity and its physiological function in adipocyte differentiation. We attribute this effect to increased interaction of RIP140 with histone deacetylases and nuclear retention of RIP140. This study uncovers a new physiological role of vitamin B6 in gene regulation by PLP conjugation to a transcriptional coregulator, which represents a new function of an old form of protein post-translational modification that has important biological consequences. PMID- 17277784 TI - Structural basis for viral late-domain binding to Alix. AB - The modular protein Alix is a central node in endosomal-lysosomal trafficking and the budding of human immunodeficiency virus (HIV)-1. The Gag p6 protein of HIV-1 contains a LYPx(n)LxxL motif that is required for Alix-mediated budding and binds a region of Alix spanning residues 360-702. The structure of this fragment of Alix has the shape of the letter 'V' and is termed the V domain. The V domain has a topologically complex arrangement of 11 alpha-helices, with connecting loops that cross three times between the two arms of the V. The conserved residue Phe676 is at the center of a large hydrophobic pocket and is crucial for binding to a peptide model of HIV-1 p6. Overexpression of the V domain inhibits HIV-1 release from cells. This inhibition of release is reversed by mutations that block binding of the Alix V domain to p6. PMID- 17277787 TI - Conditioning regimens for acute lymphoblastic leukaemia allografts. PMID- 17277788 TI - Allogeneic hemopoietic stem cell transplants for patients with relapsed acute leukemia: long-term outcome. AB - We assessed the long-term outcome of patients with relapsed acute myeloid (n=86) or acute lymphoid leukemia (n=66), undergoing an allogeneic hemopoietic stem cell transplantation in our unit. The median blast count in the marrow was 30%. Conditioning regimen included total body irradiation (TBI) (10-12 Gy) in 115 patients. The donor was a matched donor (n=132) or a family mismatched donor (n=20). Twenty-two patients (15%) survive disease free, with a median follow-up of 14 years: 18 are off medications. The cumulative incidence of transplant related mortality is 40% and the cumulative incidence of relapse related death (RRD) is 45%. In multivariate analysis of survival, favorable predictors were chronic graft-versus-host disease (GvHD) (P=0.0003), donor other than family mismatched (P=0.02), donor age less than 34 years (P=0.02) and blast count less than 30% (P=0.07). Patients with all four favorable predictors had a 54% survival. In multivariate analysis of relapse, protective variables were the use of TBI (P=0.005) and cGvHD (P=0.01). This study confirms that a fraction of relapsed leukemias is cured with an allogeneic transplant: selection of patients with a blast count <30%, identification of young, human leukocyte antigen-matched donors and the use of total body radiation may significantly improve the outcome. PMID- 17277789 TI - CMV monitoring using blood cells and plasma: a comparison of apples with oranges? AB - Quantitative cytomegalovirus (CMV) monitoring is still far from being standardized between transplant centers. In the present study, we compared assays for quantitative CMV monitoring using blood cells and plasma. Four hundred and thirty-five consecutive samples from 29 patients with active CMV infection after allogeneic T-cell-depleted hemopoietic stem cell transplantation were tested in parallel using pp65 antigenemia and quantitative CMV polymerase chain reaction (PCR) in blood cells and plasma (COBAS AMPLICOR CMV MONITOR). Although only 142 (53.1%) of 253 positive samples were concordantly identified by all three assays, the number of positive samples detected by each assay was not different and the quantitative values were correlated, provided that nucleic acid (NA) in plasma was isolated by COBAS AmpliPrep and not by the manual protocol. Six (18%) of 34 episodes with active CMV infection were not detected using CMV PCR in plasma; whereas in times of white blood cell aplasia or blast crisis of leukemia, samples with active CMV infection in plasma could not be detected using blood cells. We conclude that CMV monitoring in whole blood could be favorable compared with assays using plasma or blood cells alone. Automated NA isolation could become an attractive tool for a more sensitive and better standardized molecular diagnostics. PMID- 17277790 TI - Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group. AB - Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3 4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT. PMID- 17277791 TI - Intestinal thrombotic microangiopathy induced by FK506 in rats. AB - Thrombotic microangiopathy (TMA) is one of the severe complications after stem cell transplantation (SCT) and is associated with graft-versus-host disease (GVHD) prophylaxis including FK506. In this study, we experimented on rats using FK506 to demonstrate the occurrence of intestinal TMA. FK506 was administrated into Wistar/ST rats intraperitoneally for 7 days. Rats were examined histopathologically after FK506 injection using light and electron microscopy and immunohistochemistry. FK506 concentrations in whole blood were measured by enzyme immunoassay. In the acute phase, hemorrhagic lesions with multifocal erosions and crypt loss were found in the small intestines of all treated rats. Capillary vessels were dilated, and a few platelet thrombi were found. Electron microscopy demonstrated degenerative swelling of endothelial cells and platelet aggregates adhering to the vessel walls. In the later phase, epithelial regenerative failure, characterized by crypt ghosts, was found in the affected mucosa. Apoptotic epithelial cells were increased in number. The extent of intestinal injury was proportional to the whole blood levels of FK506. The intestinal lesions in rats were consistent with TMA and induced by the injection of FK506 alone. Apoptotic enteropathy was also observed and similar to intestinal GVHD. In this study, we established an intestinal TMA model induced by immunosuppressant (Tacrolimus) only without irradiation. PMID- 17277792 TI - Involvement of OX40 ligand+ mast cells in chronic GVHD after allogeneic hematopoietic stem cell transplantation. PMID- 17277793 TI - Analysis of factors affecting development of carpal tunnel syndrome in patients with Hurler syndrome after hematopoietic cell transplantation. AB - Children with Hurler syndrome (mucopolysaccharidosis type IH (MPSIH)) have skeletal, joint and soft tissue abnormalities that may persist or progress after hematopoietic stem cell transplantation (HSCT). We report our single center experience with development of carpal tunnel syndrome (CTS) in 43 children with MPSIH after HSCT. Twenty-three children (59%) developed CTS following HSCT; 19 of the 39 children with enzyme activity in the normal or heterozygous range developed CTS (49%), whereas all four children with low heterozygous or absent enzyme activity developed CTS after HSCT. Fourteen of 19 related donor marrow recipients, eight of 19 of those receiving an unrelated donor graft and one of five unrelated cord blood recipients developed CTS. The mean age at surgical release was 4.8 years. With each year increase in age at HSCT, there was a 55% increased risk. Age and enzyme activity after HSCT were significant factors in the development of CTS. Transplantation by 2 years of age reduced the risk of developing CTS by 46%; higher enzyme activity led to a 78% reduction in the risk of developing CTS. However, children transplanted for MPSIH remain at risk for the development of CTS, and should be monitored on an ongoing basis by nerve conduction velocity testing. PMID- 17277794 TI - Mobilization, harvesting and selection of peripheral blood stem cells in patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation. AB - Peripheral blood stem cells (PBSC) were mobilized in 130 patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation using cyclophosphamide 2 g/m(2) and either granulocyte colony-stimulating factor (G CSF) 5 mcg/kg/day (for systemic lupus erythematosus (SLE) and secondary progressive multiple sclerosis, SPMS) or G-CSF 10 mcg/kg/day (for relapsing remitting multiple sclerosis (RRMS), Crohn's disease (CD), systemic sclerosis (SSc), and other immune-mediated disorders). Mobilization-related mortality was 0.8% (one of 130) secondary to infection. Circulating peripheral blood (PB) CD34(+) cells/microl differed significantly by disease. Collected CD34(+) cells/kg/apheresis and overall collection efficiency was significantly better using Spectra apheresis device compared to the Fenwall CS3000 instrument. Patients with SLE and RRMS achieved the lowest and the highest CD34(+) cell yields, respectively. Ex vivo CD34(+) cell selection employing Isolex 300iv2.5 apparatus was significantly more efficient compared to CEPRATE CS device. Circulating PB CD34(+) cells/microl correlated positively with initial CD34(+) cells/kg/apheresis and enriched product CD34(+) cells/kg. Mean WBC and platelet engraftment (ANC>0.5 x 10(9)/l and platelet count >20 x 10(9)/l) occurred on days 9 and 11, respectively. Infused CD34(+) cell/kg dose showed significant direct correlation with faster white blood cell (WBC) and platelet engraftment. When adjusted for CD34(+) cell/kg dose, patients treated with a myeloablative regimen had significantly slower WBC and platelet recovery compared to non-myeloablative regimens. PMID- 17277795 TI - The antibiotic resistome: the nexus of chemical and genetic diversity. AB - Over the millennia, microorganisms have evolved evasion strategies to overcome a myriad of chemical and environmental challenges, including antimicrobial drugs. Even before the first clinical use of antibiotics more than 60 years ago, resistant organisms had been isolated. Moreover, the potential problem of the widespread distribution of antibiotic resistant bacteria was recognized by scientists and healthcare specialists from the initial use of these drugs. Why is resistance inevitable and where does it come from? Understanding the molecular diversity that underlies resistance will inform our use of these drugs and guide efforts to develop new efficacious antibiotics. PMID- 17277797 TI - Beyond the bench. AB - Joshua Lederberg's latest honor, the Presidential Medal of Freedom Award, recognized not only his many scientific accomplishments but those that benefited society as well. PMID- 17277796 TI - Cannibalism and fratricide: mechanisms and raisons d'etre. AB - Cannibalism and fratricide refer to the killing of genetically identical cells (siblings) that was recently documented in two Gram-positive species, Bacillus subtilis and Streptococcus pneumoniae, respectively. Cannibalism occurs during the early stages of sporulation in B. subtilis, whereas fratricide occurs in S. pneumoniae during natural genetic transformation. Here, we compare and contrast these two phenomena and discuss whether these processes are fundamentally different from the more traditional 'chemical warfare' among bacteria. PMID- 17277798 TI - The cellular world according to Hsp90. AB - An international conference focusing on the Hsp90 molecular chaperone was recently held in Seeon, Germany. The program provided a current synopsis on a wide array of topics, including structural insights, roles in established and novel cellular pathways and disease implications. PMID- 17277799 TI - Crystal structure of CETP: new hopes for raising HDL to decrease risk of cardiovascular disease? PMID- 17277800 TI - Keeping the right dosage. PMID- 17277801 TI - Tudor hooks up with DNA repair. PMID- 17277802 TI - Easing selenocysteine into proteins. PMID- 17277804 TI - Transcriptional noise and the fidelity of initiation by RNA polymerase II. AB - Eukaryotes transcribe much of their genomes, but little is known about the fidelity of transcriptional initiation by RNA polymerase II in vivo. I suggest that 90% of Pol II initiation events in yeast represent transcriptional noise, and that the specificity of initiation is comparable to that of DNA-binding proteins and other biological processes. This emphasizes the need to develop criteria that distinguish transcriptional noise from transcription with a biological function. PMID- 17277807 TI - The price of healthy eating: cost and nutrient value of selected regular and healthier supermarket foods in New Zealand. AB - AIM: To estimate the difference in cost and nutrient value for selected regular and healthier supermarket food items in New Zealand. METHOD: Electronic sales data from supermarket shoppers (n=882) from February 2004 to January 2005 were used to determine the 1000 top-selling food items. These items were categorised according to food type. Five regular items and five healthier options were selected per category to create two shopping baskets for which cost and nutrient data were then compared. RESULTS: The total weekly household cost did not differ substantially overall: NZ90.21 dollars for the regular basket vs NZ96.63 dollars for the healthy basket. However, healthier options were more expensive for some specific food categories: meat and poultry (27%); butter and margarine (44%); and cheese (19%). Healthier options were less expensive for canned fish (10%). Per unit weight, the healthier basket contained considerably less energy (29%), total fat (35%), saturated fat (52%), sugar (56%), and sodium (20%) than the regular basket. CONCLUSIONS: Cost is frequently perceived to be a barrier to a healthy diet, yet our analyses demonstrate that substantial improvements in nutrition are possible without incurring an increase in price for many staple food categories. However, healthier options within some important food categories, notably meat and spreads, are more expensive. Consideration should be given to ways in which this cost differential can be addressed to favour key healthy diet choices. PMID- 17277808 TI - Food choices among students using the school food service in New Zealand. AB - AIM: The aim of the current study is to describe the demographic characteristics and food choices of school canteen/tuckshop users. METHOD: Data for the current study were collected as part of the 2002 National Children's Nutrition Survey. 3275 students aged 5 to 14 completed a food frequency questionnaire and food habits interview. RESULTS: More than half of all students (58%) bought some or most of their food and drink from the school canteen. Among younger students, canteen users were more likely to be Maori or Pacific people and from more economically disadvantaged backgrounds. Most of the older students (74%) bought most or some of their food consumed at school from the school canteen and few demographic differences were statistically significant. Canteen use was associated with frequent consumption of some high-sugar/high-fat foods in a dose response manner, even after controlling for how much or how little food students brought from home or bought at dairies/takeaway shops. Among younger students, canteen users were significantly more likely to drink soft drinks (i.e. carbonated drinks such as cola) 5+ times a week, eat meat pies/ sausage rolls 3+ times a week, and have chocolate/sweets/lollies (candy) 4+ times a week. Older students using the school canteen were significantly less likely to eat the recommended 2 servings of fruit and 3 servings of vegetables daily and more likely to be frequent consumers of pies and sausage rolls and chocolate/sweets/lollies. CONCLUSION: As canteen use was associated with frequent consumption of some high-sugar/high-fat foods, school canteens should be encouraged to offer more healthy food options, make healthier foods cheaper and more desirable for students, and limit the availability of less healthy foods. PMID- 17277809 TI - Relationship of different measures of socioeconomic status with cardiovascular disease risk factors and lifestyle in a New Zealand workforce survey. AB - AIMS: To compare cardiovascular disease (CVD) risk factor levels of men and women in a local workforce with measures of socioeconomic (SES) status. METHODS: Participants were from a cross-sectional health screening survey of a multiracial workforce carried out between May 1988 and April 1990. 5677 Maori, Pacific Island, and Other workers (comprising 4108 men and 1569 women) aged 40 to 78 years participated. SES measures included the New Zealand Socioeconomic Index (NZSEI), combined household income, and level of education. RESULTS: In general, all SES status measures showed higher mean body mass index levels and waist-to hip ratios, higher odds of cigarette smoking, and lower stature in the lower SES strata compared to the highest SES stratum. Both income and education showed higher 5-year CVD risks and lower leisure time physical activity levels in the lower SES strata compared to the highest. The odds of raised blood pressure were highest in people with no tertiary education compared to those with a university education. Lower income groups had higher fasting and 2-hour glucose levels, higher urinary albumin excretion, and an almost 2-fold odds of diabetes mellitus compared to the highest income group. CONCLUSIONS: There was a trend to a more adverse pattern of CVD risk factor levels in the lower SES groups. The strongest associations were related to income and education rather than the NZSEI. Raised blood pressure was associated with education, and prevalence of diabetes mellitus with income. An increased living standard, more resources for primary health care, and health promotion targeting the community level should be beneficial. Effective strategies for reducing the risk level among deprived groups are needed to minimise the adverse social gradient in CVD risk factors. PMID- 17277810 TI - Indices and perception of crowding in Pacific households domicile within Auckland, New Zealand: findings from the Pacific Islands Families Study. AB - AIMS: Pacific peoples (mostly of Samoan, Tongan, Niuean, or Cook Islands origin) have a higher proportion of reported household crowding than any other ethnic group in New Zealand. However, there are multiple ways crowding can be measured. This paper reports the prevalence and concordance of Pacific peoples' own perception of household crowding together with three commonly employed indices, the American Crowding Index (ACI), Canadian National Occupancy Standard (CNOS), and Equivalised Crowding Index (ECI). METHODS: A cohort of Pacific infants born during 2000 in Auckland was followed. Maternal home interviews were conducted at 6-weeks, 12-months, and 24-months postpartum. Household membership information was obtained from the 12-month interviews. Agreement was assessed using the kappa statistic. RESULTS: In total, 1224 mothers completed the 12-month interview. Overall, 30% of mothers perceived crowding to be an issue for their households. Crowding was indicated by ACI for 37%, by CNOS for 32%, and by ECI for 59% of households. Agreement between measures ranged from poor (kappa=0.36) to moderate (kappa=0.61). In regression analyses, self-reported perception of crowding had better validity than ACI, CNOS, or ECI indices. CONCLUSION: Estimated household crowding prevalence depends on the index used. Self-reported perception of crowding appears the best measure and ECI the worst. Regardless of the index used, crowding remains an important problem for Pacific people despite recent initiatives within New Zealand. PMID- 17277811 TI - Benign papillary mesothelioma of the peritoneum in association with gastric adenocarcinoma. PMID- 17277812 TI - Cigarette pack covers (of health warnings) and individual freedom: the debate continues. PMID- 17277813 TI - More evidence for action on New Zealand's obesogenic school environment and food pricing. PMID- 17277814 TI - Percutaneous coronary intervention in New Zealand. PMID- 17277815 TI - Metabolic syndrome prevalence in a multicultural population in Auckland, New Zealand. AB - OBJECTIVE: To estimate ethnic-specific metabolic syndrome prevalence in the Auckland region and to identify the main reasons for the differences. METHODS: A cross-sectional survey of adults aged between 35-74 years within the Auckland area using a dual sampling frame with both cluster sampling and random selection from electoral rolls. Participants included 1006 Maori, 996 Pacific people, and 2020 of other ethnicity (mainly Europeans). RESULTS: The prevalence of metabolic syndrome (using the 2001 ATPIII definition, age and gender adjusted) were: Maori 32%, Pacific people 39%, and Others 16%. Maori were twice as likely as others (OR=2.01, 95% CI: 1.53 to 2.64) to have the metabolic syndrome while Pacific people were two and a half times as likely (OR=2.54, 95% CI: 1.93 to 3.35), after adjusting for multiple CVD risk factors other than the components of the syndrome. Adjusting these ethnic differences in prevalences for each of the components of the syndrome separately indicated that most of the differences could be accounted for by differences in obesity. In addition, more than a third of people with diabetes did not have the metabolic syndrome. CONCLUSIONS: The prevalences of metabolic syndrome were significantly higher in Pacific people and Maori compared to Others and measures of obesity accounted for most of the ethnic differences. PMID- 17277816 TI - Endotoxin and indoor allergen levels in kindergartens and daycare centres in Wellington, New Zealand. AB - AIMS: A large majority of children in New Zealand attend daycare centres and kindergartens early in life. Overseas studies have demonstrated a possible protective effect of daycare attendance against asthma and allergy later in life. One hypothesised agent for this protection is high levels of endotoxin, which have not previously been measured in New Zealand childcare facilities. The purpose of this study was to measure endotoxin and indoor allergens in kindergartens and daycare centres in the Wellington region. METHODS: Dust samples were collected from 18 kindergartens and 18 daycare centres and analysed for endotoxin by the kinetic limulus amebocyte lysate assay and for indoor allergens by double monoclonal/polyclonal antibody ELISA. RESULTS: The geometric mean level (95% CI) was 29,206 EU/g (19,410-43,950) for endotoxin, 0.25 mcg/g (0.04-2.28) for Der p 1, 1.24 mcg/g (0.80-1.90) for Fel d 1, 0.43 mcg/g (0.26-0.71) for Can f 1, and 0.028 mcg/g (0.020-0.039) for Bla g 2. CONCLUSIONS: Endotoxin levels in daycare centres and kindergartens in Wellington, New Zealand are similar to domestic dwellings in Wellington, however indoor allergen levels are much lower. The low indoor allergens in the daycare centres and kindergartens are unlikely to be problematic for sensitised infants, although some individual childcare facilities had very high Der p 1 levels. PMID- 17277818 TI - Colchicine overdose: the devil is in the detail. AB - Colchicine, a highly poisonous alkaloid, is a commonly used treatment for gout, Bechet's disease, and familial Mediterranean fever. Despite the knowledge of its side effects, the near universally fatal consequence of a significant overdose is commonly under-appreciated. In this report, we present a case series of 9 patients over the past 15 years (from within the Auckland region of New Zealand) that have presented with a colchicine overdose. Surprisingly, a significant number were accidental overdoses and all cases, apart from one, resulted in death. We question the current knowledge base about the toxicity of this drug amongst prescribers, patients, and their families and its use in the treatment of acute gout. Given its extremely narrow therapeutic index, should the manner in which medical practitioners prescribe this drug be reassessed? PMID- 17277819 TI - Medical image. Tularaemic cervical lymphadenopathy. PMID- 17277817 TI - Metabolic control with insulin pump therapy: the Waikato experience. AB - AIM: To report the effect of insulin pump therapy on glycaemic control and on hypoglycaemia and ketosis rates in Type 1 diabetic patients. METHODS: A retrospective audit of the management of patients with Type 1 diabetes treated with insulin pump therapy at the Waikato Diabetes Service (Hamilton, New Zealand) between September 1997 and December 2004. RESULTS: The data of 105 patients currently on continuous subcutaneous insulin infusion (CSII) at the time of data collection were examined. CSII use had occurred for a mean of 3.0+/-2.6 years. HbA1c% improved significantly from 8.9+/-1.3% to 7.9+/-1.0% (P<0.001) at 3 months and 7.9+/-0.95% (P<0.001) at 6 months post CSII. This reduction was maintained after 1, 2, and 3 years and the difference was statistically significant (P<0.001). In the adolescent subgroup (n=27) we observed a similar significant reduction in HbA1c% that was maintained after 1 year of pump therapy. The incidence of severe hypoglycaemia was reduced from 0.75 cases per patient-year during multiple daily injection (MDI) pre-pump to 0.05 cases per patient-year during CSII (P<0.001). In some cases hypoglycaemia awareness was restored. There was no evidence to suggest increased tendency for diabetic ketoacidosis (DKA) with continuing use of insulin pumps. Conclusion Our experience showed that insulin pump therapy was effective and safe for both adults and adolescents with Type 1 diabetes. The reduction in HbA1c% was both statistically and clinically highly significant. Wider usage of this technology in New Zealand is warranted. PMID- 17277820 TI - An opinion on elective and acute care services in New Zealand. PMID- 17277821 TI - Silane based concepts on bonding resin composite to metals. AB - INTRODUCTION: The longevity of silane promoted adhesion of surface conditioned metallic materials is of concern in dentistry and poses both a functional and esthetic dilemma for the patient and dental professionals. Several methods for surface conditioning exist, but some are employed more frequently in clinical practice. AIM OF THE REVIEW: This overview aims to characterize and discuss the most commonly used surface conditioning methods based on silanization. The primary chemical features in silane treatment will also be presented. METHOD OF REVIEW: The literature regarding silane utilization was systematically selected and 68 cited references published during 1967-2005 were reviewed. Technical descriptions of different silica-coating (silicatization) methods are presented and some comparative clinical and in vitro experiences are reported. Some other surface condition methods applied in dental laboratories were also selected for presentation. CONCLUSION: It is concluded in this overview tribochemical silica coating followed by a mandatory silane coupling agent application is a clinically proved, relevant adhesion promotion method to enhance the bonding of resin composites to metallic dental materials. PMID- 17277822 TI - Fatigue strength of fragmented incisal edges restored with a fiber reinforced restorative material. AB - AIM: The aim of this study was to determine the compressive fatigue limits (CFLs) of fractured incisor teeth restored using either a conventional adhesive composite technique or using fiber-reinforced composites (FRCs). METHODS AND MATERIALS: Fifteen extracted sound upper incisor teeth were prepared by cutting away the incisal one-third part of their crowns horizontally. The teeth were restored using three techniques. Group A (control group) was restored by reattaching the original incisal edge to the tooth. Group B was restored using particulate filler composite (PFC). Group C was restored with PFC and FRC by adding a thin layer of FRC to the palatal surface of the teeth. The bonding system used was a conventional etch system with primer and adhesive. All restored teeth were stored in water at room temperature for 24 h before they were loaded under a cyclic load with a maximum controlled regimen using a universal testing machine. The test employed a staircase approach with a maximum of 103 cycles or until failure occurred. Data were analyzed using analysis of variance (ANOVA) (p=0.05). Failure modes were visually examined. RESULTS: Group A (reattaching fractured incisal edge) revealed the lowest CFL values, whereas the creation of a new incisal edge with PFC revealed a 152% higher CFL value compared to Group A. Group C (teeth restored with FRC) revealed a 352% higher CFL than the control group. ANOVA revealed the restoration technique significantly affected the compressive fatigue limit (p<0.001). The failure mode in Group A and B was debonding of the restoration from the adhesive interface. While in Group C, the sample teeth fractured below their cemento-enamel junctions. CONCLUSION: These results suggested an incisally fractured tooth restored with the combination of PFC and FRC-structure provided the highest CFL. PMID- 17277823 TI - The effect of thermocycling on the adhesion of self-etching adhesives on dental enamel and dentin. AB - AIM: The aim of the present study was to investigate the effectiveness of one total-etch self-priming adhesive and two one-step self-etching adhesive systems on the adhesion of a resin composite to both dentin and enamel. The effect of thermocycling on the adhesion was also investigated. The null hypothesis tested was thermocycling would not affect bond strengths to enamel and dentin treated with self-etching adhesives or a total-etch adhesive. METHODS AND MATERIALS: Two single-step self-etching adhesives [Xeno III (XE3) and Prompt L-Pop (PP)] and one two-step total-etch adhesive system (Prime & Bond NT) (P&B NT) were used in this study. Thirty caries-free unrestored human third molars were used to make specimens of enamel and dentin. Different adhesives were applied on enamel and dentin surfaces according to the manufacturer's instructions then hybrid composite restorative material was condensed on the surface using a mold. The bonded specimens were stored in distilled water at 37 masculineC for 24 hours before being tested. Half of the bonded specimens were tested for shear bond strength without thermocycling. The other half of the test specimens were thermocycled using a thermocycling apparatus in water baths held at 5 masculineC and 55 masculineC with a dwell time of one minute each for 10,000 cycles prior to shear testing. The mean shear bond strength before and after thermocycling was calculated, and the results were subjected to two-way analysis of variance (ANOVA) and repeated measure design to show the interaction between different materials and different times. RESULTS: The results showed shear bond strength on both enamel and dentin of the total-etch adhesive and the self-etching adhesives decreased after the specimens were subjected to thermocycling. CONCLUSIONS: The null hypothesis tested "thermocycling would not affect bond strengths treated with self-etching adhesives" was rejected. Furthermore, the study revealed the following: 1. The shear bond strength to both enamel and dentin of the total-etch adhesive and the self-etching adhesives decreased after the specimens were subjected to thermocycling. 2. XE3 achieved the highest bond strength to both enamel and dentin (26.994+/-1.17 and 25.22+/-1.26, respectively). 3. XE3 showed even better bonding after thermocycling to enamel and dentin than the total etching system or PP. 4. Although PP bonded to enamel showed lower shear bond strength value than XE3, it has durable bond strength even after thermocycling. PMID- 17277824 TI - Shear bond strength of resin modified glass ionomer cement bonded to different tooth-colored restorative materials. AB - AIM: The aim of this study was to determine in vitro the shear bond strength (MPa) and the type of bond failure when resin-modified glass ionomer cement (RMGIC) was bonded with different tooth-colored restorative materials. METHODS AND MATERIALS: The RMGIC tested was Fuji II LC (FL) and the tooth-colored restorative materials used were composite resin Point-4 (P4), Compomer Dyract AP (DY), and Ormocere Admira (AD). A total number of 60 FL specimens were prepared using Teflon molds. The specimens were divided into six equal groups. Each group of ten specimens was bonded to a tested tooth-colored restorative material as follows: Group I--etched FL bonded to P4; Group II--non-etched FL bonded to P4; Group III--etched FL bonded to DY; Group IV--non-etched FL bonded to DY; Group V- etched FL bonded to AD; and Group VI--non-etched FL bonded to AD. The specimens were stored in distilled water at 37 degrees C for 24 hours. The shear bond strength was measured in a universal testing machine, and the fractured surfaces were examined under a stereomicroscope. RESULTS: The results of the shear bond strength indicated the lowest mean value (14.46 MPa) was in Group III, and this was significantly different from the values of other groups (p<0.05). However, Groups V and VI recorded the highest mean values (24.5 MPa and 28.39 MPa) which were significantly different (p<0.05) when compared to other groups. Groups I, II, and IV showed no significant difference with mean values of 20.06, 19.99, and 20.1 MPa which were significantly different from other groups (p<0.05). CONCLUSION: AD showed the highest shear bond strength to RMGIC. All groups demonstrated a cohesive failure in FL except for Group IV where a cohesive failure in DY was recorded. AD showed good shear bond strength when laminated with FL. PMID- 17277825 TI - Effectiveness of second-generation light-emitting diode (LED) light curing units. AB - AIM: The purpose of this study was to evaluate the effectiveness of three commercially available light emitting diode (LED) light curing units (LCU) (Elipar FreeLight--3M ESPE; UltraLume LED2--Ultradent; and Single V--BioArt) for polymerizing Z250-A3 composite (3M ESPE) using Knoop hardness, polymerization depth, and flexural strength properties. METHODS AND MATERIALS: The XL 2500 (3M ESPE) LCU, which is a conventional halogen unit, was used as a control. In all cases the curing time was 20 seconds. Hardness was determined 24 hours after composite cure for 10 samples of 8 mm diameter and 2 mm height for each LCU tested. Samples were stored dry in a light-proof container prior to testing. The depth of cure of the composite was measured immediately after composite polymerization for each LCU using three samples 4 mm in diameter and 6 mm in height. Flexural strength was determined for five samples 24 hours after immersion in distilled water at 37 degrees C. Each sample measured 25 mm in length, 2 mm in width, and 2 mm in height for each LCU tested. CONCLUSION: The results were treated statistically for comparison of the LCUs. In all cases the results obtained by LED LCUs were not different or were higher than a conventional halogen LCU. CLINICAL SIGNIFICANCE: Second generation LED LCUs were as effective as/or more effective than a halogen LCU for polymerization of the used composite. The present study shows second generation LEDs have the potential to replace halogen LCUs. PMID- 17277826 TI - Radiometric and spectrophotometric analysis of third generation light-emitting diode (LED) light-curing units. AB - AIMS: Light-emitting diode (LED) polymerization of dental restorative materials has become increasingly popular. However, individual light-curing unit (LCU) functions (intensity and/or wavelength emission) may not conform to manufacturer specifications due to quality control issues. The purpose of this study was to evaluate the quality of irradiance, in terms of power density (intensity) and spectral distribution (peak wavelength), emitted from LED and quartz-tungsten halogen (QTH) LCUs in vitro. The battery expenditure of these LED units was also tested. METHODS AND MATERIALS: The intensity and spectral distribution from four third generation LED (Smartlite PS, Coltolux LED, radii Plus, Diopower) and one QTH (Schein Visible Cure) light sources were measured using six different dental curing light meters (Coltolux, Cure Right, Demetron 100, Demetron LED., Hilux, and Light Meter-200) and a visible-ultraviolet light spectrophotometer (Hitachi Elmer-Perkins). The battery life was also plotted for each light source following a 1500 second duration period. The data obtained from radiometric and spectrophotometric analysis was compared to manufacturer specifications. RESULTS: Radiometric evaluation revealed LED light units tested did not satisfy manufacturer claims for minimum intensities. Spectral emissions from the LED light sources did meet manufacturer requirements. No clinically appreciable battery drain was evidenced from testing all re-chargeable LED units. CONCLUSION: Despite limitations LED technology appears to be an effective alternative for curing of light-activated esthetic restorative materials. Additional advantages associated with LED curing lights include ergonomic handling capabilities, negative heat generation, and minimal maintenance concerns. PMID- 17277827 TI - The Knoop hardness of a composite resin polymerized with different curing lights and different modes. AB - AIM: The purpose of this study was to compare the surface hardness of a hybrid composite resin polymerized with different curing lights. METHODS AND MATERIALS: Two 3.0 mm thick composite resin discs were polymerized in a prepared natural tooth mold using: (1) a conventional quartz-tungsten halogen light (QTH- Spectrum 800); (2) a high-intensity halogen light, Elipar Trilight (TL) standard/exponential mode; (3) a high-intensity halogen light, Elipar Highlight (HL)-standard/soft-start mode; (4) a light-emitting diode, Elipar Freelight (LED); and (5) a plasma-arc curing light, Virtuoso (PAC). Exposure times were 40 seconds for the halogen and LED lights, and three and five seconds for the PAC light. Following polymerization, the Knoop hardness was measured at the bottom and the top surfaces of the discs. RESULTS: Significant differences were found between top and bottom Knoop Hardness number (KHN) values for all lights. The hardness of the top and bottom surfaces of both specimens cured by the PAC light was significantly lower than the other lights. No significant hardness differences were observed between the remaining curing units at the top of the 2.0 mm specimens. Significant differences were found between the LED and two modes of HL on the bottom surfaces. For the 3.0 mm thick samples, while significant differences were noted between LED and TL standard mode and between the two TL curing modes on the top, significant differences were only observed between QTH and the standard modes of TL and HL at the bottom. PMID- 17277828 TI - Gap formation between different cavity walls and resin composite systems on primary and permanent teeth. AB - AIM: The aim of this study was to compare the effectiveness of five self-etching and etch-rinse dentin-bonding agents in achieving a gap-free adaptation between the restorative material and the dentin in primary and permanent teeth. METHODS AND MATERIALS: Gaps located at the restoration dentin interface were evaluated using scanning electron microscopy (SEM). RESULTS: There were more gaps on the corner of the cavities, but no significant difference was detected between different cavity walls (p>0,05). Statistical results of the SEM analysis revealed fewer gaps in the restorations made with self-etching dentin bonding agents than etch-rinse agents at the restoration-dentin interface in both primary and permanent teeth. CONCLUSION: Self-etching bonding systems were preferable in primary and permanent teeth according to the results of this study. However, further studies should be conducted to determine a favorable strategy to eliminate the gaps on the corners of cavities and maintain a gap-free adaptation between resin composite and tooth structure. PMID- 17277829 TI - Effect of photoactivation systems and resin composites on the microleakage of esthetic restorations. AB - AIM: The aim of this study was to evaluate the influence of four photoactivation systems [quartz tungsten halogen (QTH), light-emitting diode (LED), argon ion laser (AL), and plasma arc curing PAC)] on cementum/dentin and enamel microleakage of Class II restorations using a microhybrid [Z250-3M ESPE] and two packable composites [(SureFil-Dentsply and Tetric Ceram HB-Ivoclair/Vivadent]. METHODS AND MATERIALS: Three hundred sixty "vertical-slot Class II cavities" were prepared at the mesial surface of bovine incisors using a 245 carbide bur in a highspeed handpiece. Specimens were divided into twelve groups (composite photoactivation systems). Half of the specimens had the gingival margin placed in enamel (n=15) and the other half in cementum/dentin (n=15). Composites were inserted and cured in 2 mm increments according to manufacturers' recommended exposure times. After polishing, the samples were immersed in 2% methylene blue solution, sectioned, and evaluated at the gingival margins. Data were submitted to statistical analysis using the Kruskal-Wallis and Mann-Whitney tests. RESULTS: No significant differences were found among the photoactivation systems and among resin composites (p>0.05). Microleakage was not significantly affected by location (enamel vs. cementum/dentin, p>0.05). These findings suggested neither the photoactivation systems nor the resin composite types might have an effect on the microleakage at gingival margins Class II cavities. PMID- 17277830 TI - Effect of two light-emitting diode (LED) and one halogen curing light on the microleakage of Class V flowable composite restorations. AB - AIM: The disadvantages of light cured composite resin materials with respect to microleakage are predominantly a result of polymerization shrinkage upon curing. It has been shown curing methods play a significant role in polymerization shrinkage of light-cured composite resins. The purpose of this study was to investigate the effect of light-emitting diode (LED) light curing units (LCUs) compared with a halogen LCU on microleakage of three different flowable composites using self-etch adhesives. METHODS AND MATERIALS: A total of 63 extracted human premolars were prepared with standardized Class V cavity preparations on the buccal and lingual surfaces of each tooth. The occlusal margin of the cavities was located on the enamel and the gingival margin was on dentin. Teeth were randomly assigned to three groups of 21 teeth each as follows: Group 1: Adper Prompt L-Pop + Filtek Flow (3M ESPE); Group 2: AdheSE + Tetric Flow (Ivoclar, Vivadent); and Group 3: Clearfil Protect Bond + Clearfil Protect Liner F (Kuraray Medical Inc.). All the groups were subdivided into three groups according to the curing lights used (n=7). Two LED LCUs, Elipar FreeLight and Elipar FreeLight 2 (3M ESPE), and one halogen-based LCU, Hilux Expert (Benlioglu ), were used. All teeth were then immersed in 0.5% basic fuchsin dye solution for 24 hours after thermocycling (500 cycles; between 5 degrees C to 55 degrees C). The teeth then were longitudinally sectioned and observed under a stereomicroscope (40X magnification) by two examiners. The degree of dye penetration was recorded separately for enamel and dentin. Data were analyzed with the Kruskal-Wallis and Mann-Whitney tests with the Bonferroni correction. RESULTS: No statistically significant differences in microleakage were observed between groups either on enamel or dentin (p>0.05). CONCLUSION: With the limitation of this in vitro study, the differences in microleakage between LCUs used were not statistically significantly different. Elipar Free Light 2 reduces curing time which can be considered as an advantage. PMID- 17277831 TI - The effect of different finishing and polishing systems on the surface roughness of different composite restorative materials. AB - AIM: The purpose of this in vitro study was to examine the effect of two different finishing systems on the surface roughness of different types of composite restorative materials. METHODS AND MATERIALS: Thirty specimens, 8 mm in diameter and 3 mm in depth, were prepared using a microfill composite (Clearfil ST, Kuraray Co. Ltd., Osaka, Japan), a hybrid composite (Clearfil AP-X, Kuraray Co. Ltd., Osaka, Japan), and a packable composite (Clearfil Photo Posterior, Kuraray Co. Ltd., Osaka, Japan) cured against a Mylar matrix strip to create a baseline surface. The average surface roughness was measured using a surface profilometer (Surftest 211, Mitutoyo, Japan) in five different positions on each sample before and after finishing with one of the two finishing systems [Sof-Lex discs (3M) and Po-Go (Dentsply)]. The obtained data were analyzed by two-way analysis of variance (ANOVA) at a p=0.05 significance level. RESULTS: There were statistically significant differences in the average surface roughness (Ra, microm) between the Mylar matrix strip, Sof-Lex discs, and Po-Go discs (p<0.05). For all tested materials, the Mylar matrix strip provided smoother surfaces than both of the finishing systems (p<0.05). When the finishing discs were compared, Sof-Lex discs produced a smoother surface than Po-Go discs for all tested materials (p<0.05). CONCLUSION: The Mylar matrix strip provided a smoother surface than Sof-Lex and Po-Go discs. Furthermore, Sof-Lex discs produced smoother surfaces than Po-Go discs. Sof-Lex and Po-Go systems produced clinically acceptable surface roughness for microfill, hybrid, and packable composite resin materials. The effect of finishing and polishing systems on surface roughness was dependent on both the system and the composite resin restorative material. PMID- 17277832 TI - The influence of commercially pure titanium and titanium-aluminum-vanadium alloy on the final shade of low-fusing porcelain. AB - AIMS: The aims of this study were to investigate the influence of commercially pure titanium (PTi) and titanium-aluminum-vanadium (Ti-6Al-4V) alloys (TiA) on the final shade of low-fusing porcelain bonded to them and to compare the shade changes with those of three conventional metal-ceramic systems. METHODS AND MATERIALS: A titanium casting unit was used to cast PTi and Ti-6Al-4V alloy specimens followed by A3 shade low-fusing porcelain (Noritake) being bonded to them. Gold-based (AuA), palladium-based (PdA), and nickel-chromium (Ni-Cr) alloys were cast with an automatic centrifugal casting machine, then A3 shade conventional porcelain material (Vita, VMK 95) was applied to them. Ten specimens of each metal were then fabricated. The CIE L* a* b* color coordinates of the specimens were measured with a spectrophotometer. RESULTS: All alloys had significant color changes when compared with A3 shade tabs. The color differences from the shade tabs were 5.79 for the Ti-6Al-4V group, 6.46 for PdA alloy, 8.12 for AuA alloy, 8.15 for Ni-Cr alloy, and 12.58 for PTi. The specimens differed from the shade tabs primarily because of the differences in a* and b* coordinate values. CONCLUSIONS: Predictable shade reproduction of metal-ceramic restorations (MCRs) may be impaired by the underlying metal. The PTi had the greatest color differences among all the tested metal when compared with the shade tabs, whereas the Ti-6Al-4V alloy had the lowest. PTi is more likely to affect the final shade of low-fusing porcelain than Ti-6Al-4V alloy. PMID- 17277833 TI - A comparison of two different methods and materials used to repair polycarbonate crowns. AB - AIM: The aim of this study was to evaluate the bond strength and crown-repair material interface of polycarbonate crown repaired using flowable resin composite and hybrid resin composite following two different surface preparations. METHODS AND MATERIALS: The facial surfaces of fifty-two polycarbonate crowns were flattened and roughened. Specimens were then divided into four test groups. A bonding agent alone (Groups 1 and 2) or a combination of methylmethacrylate (MMA) + bonding agent (Groups 3 and 4) was applied to the prepared surfaces. Then either a flowable (Groups 1 and 3) or a microfilled hybrid (Groups 2 and 4) resin composite was placed on the surfaces. Forty-eight of the original fifty-two specimens were used for shear bond strength testing. Failure types (adhesive, cohesive, and mixed) were evaluated. The remaining four specimens, one from each group, were used for crown-resin composite interface analysis using a scanning electron microscope (SEM). RESULTS: There were significant differences in both mean shear bond strength values and failure types (P<0.05). The SEM evaluation revealed a close interface relationship in Groups 3 and 4. CONCLUSION: MMA monomer application on a polycarbonate crown prior to application of an adhesive agent improved the shear bond strength of the repair material. PMID- 17277835 TI - Split-increment technique: an alternative approach for large cervical composite resin restorations. AB - AIM: This article proposes and describes the split-increment technique as an alternative for placement of composite resin in large cervical carious lesions which extend onto the root surface. TECHNIQUE: Two flat 1.5 mm thick composite resin increments were used to restore these cervical carious lesions. Prior to light-curing, two diagonal cuts were made in each increment in order to split it into four triangular-shaped flat portions. The first increment was applied to cover the entire axial wall and portions of the four surrounding walls. The second increment was applied to fill the cavity completely covering the first one and the rest of the four surrounding walls as well as sealing all cavity margins. CLINICAL SIGNIFICANCE: This technique results in the reduction of the C-factor and the generated shrinkage stresses by directing the shrinking composite resin during curing towards the free, unbonded areas created by the two diagonal cuts. The proposed technique would also produce a more naturally looking restoration by inserting flat dentin and enamel increments of composite resin of a uniform thickness which closely resembles the arrangement of natural tooth structure. PMID- 17277834 TI - Effect of centripetal and incremental methods in Class II composite resin restorations on gingival microleakage. AB - AIM: The aim of this study was to evaluate the microleakage at gingival margins below the cementoenamel junction (CEJ) of Class II composite restorations using various placement techniques. METHODS AND MATERIALS: Sound human maxillary premolars were selected. Eighty slot-style cavities on the mesial or distal surfaces were prepared with the cervical margins located apical to the CEJ. The specimens were divided into two groups based on the restorative technique utilized (centripetal or incremental). Each group was then categorized into two subgroups according to the type of matrix used resulting in a total of four experimental groups as follows: IP=Incremental and Palodent matrix, IT = Incremental and Transparent matrix, CP= Centripetal and Palodent matrix, and CT = Centripetal and Transparent matrix. Following restoration with a total etch adhesive (Single Bond) and a resin composite (Z100), the teeth were thermocycled. Then specimens were immersed in 0.5% basic fuchsin dye for 24 hours at a temperature of 37 degrees C. Sectioned restorations were examined under a stereomicroscope (40X magnification), and the extent of the microleakage was scored and recorded. Data were analyzed using the Kruskal-Wallis non-parametric statistical test (P=0.05). RESULTS: In the four groups of the study no significant differences in the mean rank of microleakage were observed (p>0.05). CONCLUSION: When the gingival margin was located on cementum, the kind of matrix and filling technique did not reduce the microleakage. PMID- 17277836 TI - Time-resolved methods in biophysics. 4. Broadband pump-probe spectroscopy system with sub-20 fs temporal resolution for the study of energy transfer processes in photosynthesis. AB - In this paper we discuss how to push the temporal resolution limits of transient absorption spectroscopy in order to detect very fast processes (energy relaxation, energy or charge transfer, vibrational coherence) taking place in molecules of biological relevance. After reviewing the main principles of femtosecond pump-probe spectroscopy, we describe an experimental setup based on two synchronized non-collinear optical parametric amplifiers (NOPAs). Each NOPA can be independently configured to generate ultra-broadband sub-10 fs visible pulses, tunable 10-15 fs visible pulses, tunable 15-40 fs near-infrared pulses (900-1500 nm). This system enables to perform pump-probe experiments over nearly two octaves of spectrum with sub-20 fs temporal resolution. We then present an application example highlighting the capability of this instrument to track excited state dynamics in biomolecules on the sub-100 fs timescale: the study of carotenoid-bacteriochlorophyll energy transfer processes in peripheral light harvesting complexes (LH2) from purple bacteria. We show that, by comparing excited-state dynamics of the carotenoids in organic solvents and inside the LH2 complexes, it is possible to visualize in the time domain the primary events in photosynthesis. PMID- 17277837 TI - Relation between intracellular location and photodynamic efficacy of 5 aminolevulinic acid-induced protoporphyrin IX in vitro. Comparison between human glioblastoma cells and other cancer cell lines. AB - A promising clinical application of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PP IX) is fluorescence detection and photodynamic treatment of residual tumour tissue during surgical resection of high grade malignant glioma. U373 MG human glioblastoma cells were used as a model system to study the relation between intracellular location and photodynamic efficacy of 5-ALA induced PP IX in more detail. Therefore, ultra-sensitive fluorescence microscopy, using either optical excitation of whole cells or selective excitation of the plasma membrane by an evanescent electromagnetic field, was combined with quantitative measurements of intracellular porphyrin amount and phototoxicity. Glioblastoma cells accumulated PP IX to a moderate extent as compared to T47D breast cancer cells (high accumulation) or OV2774 ovarian cancer cells (low accumulation). Although photodynamic inactivation of the different cell lines (decreasing in the order T47D > U373 MG > OV2774) seemed to be directly related to PP IX accumulation, examination of the data in more detail revealed that photodynamic efficacy per photosensitizer molecule (PE) was about two times higher in glioblastoma and ovarian cancer cells as compared to breast cancer cells. The different photodynamic efficacy of PP IX was related to the different intracellular location. In contrast to breast cancer cells where PP IX fluorescence was localized in small granules, PP IX fluorescence in glioblastoma cells and ovarian cancer cells originated mainly from cellular membranes. Thus, the intracellular location of PP IX in a predominantly lipophilic environment, characterized by a comparably high photostability (probed by photobleaching and photoproduct formation) and a lower degree of porphyrin aggregation (probed previously by fluorescence decay kinetics), seems to be the key factor for high photodynamic efficacy of 5-ALA-induced PP IX. In the case of OV2774 ovarian cancer cells, however, a low PP IX accumulation limited cell inactivation upon irradiation, whereas the results obtained for glioblastoma cells are encouraging to develop PDT to an additional therapeutic option for the treatment of tumour margins in patients who underwent fluorescence-guided resection of high grade malignant glioma after 5-ALA administration. PMID- 17277838 TI - Effect of the labelling ratio on the photophysics of fluorescein isothiocyanate (FITC) conjugated to bovine serum albumin. AB - The non-linearity of the fluorescence emission on increasing the probe to protein ratio has long been regarded as problematic and has lead to the development of dyes to overcome this effect. One of the causes of this non-linear response can be ascribed to the overlap of the label's own absorption and emission spectra. At higher labelling ratios, this affords the possibility of a reasonably efficient energy migration pathway, thus reducing the observed quantum yield of the dye. In this work we study the photophysics of fluorescein isothiocyanate (FITC) when conjugated to bovine serum albumin (BSA) at different labelling ratios (in the range FITC : BSA 1 : 17-15 : 1) using both steady state and time-resolved fluorescence techniques where on going from under labelled to over labelled samples a decrease in the initial (and steady state) anisotropy is observed, accompanied by an increase in the complexity of the decay kinetics and a decrease in the average lifetime. The band structure, elucidated by synchronous scan fluorescence spectroscopy, is also found to change on increased labelling. These results can be applied to the study of protein conformation and were confirmed by the analysis of denaturing BSA using urea. PMID- 17277839 TI - Support-controlled chemoselective olefin-imine addition photocatalyzed by cadmium sulfide on a zinc sulfide carrier. AB - The semiconductor catalyzed photoaddition of cyclopentene or cyclohexene to various novel electron-poor imines of type p-XC(6)H(4)(CN)C[double bond, length as m-dash]N(COPh) (X = H, F, Cl, Br, Me, MeO) was investigated as a function of the nature of the cadmium sulfide photocatalyst. Irradiation (lambda>/= 350 nm) of silica supported cadmium sulfide surprisingly did not afford the expected olefin-imine adducts but an imine hydrocyanation product via an unprecedented dark reaction. However, when silica was replaced by zinc sulfide as the support for cadmium sulfide, the expected homoallylic N-benzoyl-alpha-amino cyanides were isolated in yields of 65-84%. Thus, chemoselectivity is introduced through replacing an insulating by a semiconducting support, a hitherto unknown effect in semiconductor photocatalysis. From the sign of the time resolved photovoltage it is found that the mixed metal sulfide interface CdS/ZnS increases the lifetime of photogenerated electron-hole pairs by about one order of magnitude as compared to the SiO(2)/CdS system. The reaction rate increases with increasing imine sigma Hammett constants and decreasing stability of intermediate benzyl radicals. PMID- 17277840 TI - Visible-light induced hydrogen production using a polypeptide-chlorophyll complex with alpha-helix conformation. AB - Hydrogen production was accomplished under visible-light irradiation by using a system consisting of a biomolecule (chlorophyll a), methylviologen, ethylenediaminetetraacetic acid disodium salt and Pt-loaded poly(l-glutamate) (Poly(Glu)), in aqueous decylammonium chloride (DeAC) solution. Spectroscopic studies revealed that chlorophyll a is solubilized in the hydrophobic clusters of Pt-loaded Poly(Glu)-decylammonium chloride. In the Poly(Glu)-DeAC complex, the electron transfer occurred between chlorophyll a and methylviologen leading to hydrogen production. The most noticeable result is that the rate of hydrogen evolution depends on the change from the random coil to the alpha-helix in conformation of Poly(Glu) induced by the cooperative binding with DeAC. PMID- 17277841 TI - Photodegradation mechanism and reaction kinetics of recombinant human interferon alpha2a. AB - The photodegradation mechanism of recombinant human interferon-alpha2a (IFNalpha2a) has been investigated using absorption, fluorescence, and circular dichroism (CD) spectroscopies, and fluorescence photobleaching kinetics measurements under various conditions. After photobleaching, the absorption profile of aromatic amino acid residues in IFNalpha2a was almost absent, and an absorption profile showing a monotonic increase toward short wavelengths was observed. According to the CD spectrum analysis, partial unfolding of IFNalpha2a was accompanied by a complete loss of fluorescence. This unfolding was attributed to tryptophan-mediated photoinduced disulfide bond cleavage. Photooxygenation and photoionization of tryptophan (Trp) residues followed by subsequent radical reactions were the main photodegradation pathways of IFNalpha2a. Photobleaching kinetics was faster in acidic solution (pH 2.5) than in neutral solution (pH 7.4). The variation of photobleaching kinetics seemed to be caused by the structural differences in IFNalpha2a according to the solution pH. The relationship between the protein conformation and photobleaching rate could be explained based on the competition between excited state energy transfer and the photoionization process in Trp residues. PMID- 17277842 TI - Rufloxacin-induced photosensitization in yeast. AB - The fluoroquinolone Rufloxacin (RFX) is active as specific inhibitor of bacterial gyrase. The adverse effects of the photosensitization induced by fluoroquinolones are well known. A predominant type II photosensitizing activity of Rufloxacin has already been demonstrated on simpler models (free nucleosides, calf thymus DNA), whereas a cooperative mechanism was corroborated on more complex ones (plasmid and fibroblast). The purpose of this study is to examine the drug photocytoxicity in another complex cellular model, a wild-type eukaryotic fast-growing microorganism whose cultivation is cheap and easily managed, Saccharomyces cerevisiae. This work represents the first report of the potential photogenotoxicity of Rufloxacin. Particular emphasis was given to DNA modifications caused in yeast by the formation of Rufloxacin photomediated toxic species, such as hydrogen peroxide and formaldehyde. Drug phototoxicity on yeast was evaluated by measuring DNA fragmentation (single/double strand breaks) using single cell gel electrophoresis assay and 8-OH-dGuo, a DNA photooxidation biomarker, by HPLC-ECD. Cellular sensitivity was also assessed by cell viability test. The extra- and intracellular RFX concentration (as well as its main photoproduct) was verified by HPLC-MS, whereas the cytotoxic species were evaluated by colorimetric assays. The results confirm the phototoxicity of Rufloxacin on yeast cell and are in agreement with those previously obtained with human fibroblast and with simpler models used recently, and provide a clear link between DNA photosensitization and overall phototoxicity. PMID- 17277843 TI - UV screening in higher plants induced by low temperature in the absence of UV-B radiation. AB - Epidermally located UV-B absorbing hydroxycinnamic acid derivatives and flavonoids serve as a screen against potentially damaging UV-B (280-315 nm) radiation in higher plants. We investigated the effect of low temperature on epidermal screening as assessed by a chlorophyll fluorescence technique. The epidermal UV-transmittance of greenhouse-grown Vicia faba plants was strongly dependent on growth temperatures between 21 and 9 degrees C, with significant differences already between 21 and 18 degrees C. There was a good correlation between epidermal UV-A and UV-B absorbance and the absorbance of whole leaf extracts at the respective wavelengths. Whereas in Oxyria digyna and Rumex longifolius no temperature dependence of epidermal transmittance could be detected, it was confirmed for seven other crop plant species, including summer and winter varieties, and for Arabidopsis thaliana. Dicotyledoneous plants showed a stronger response than monocotyledoneous ones. In all investigated species, the response in the UV-A spectral region was similar to that in the UV-B, suggesting that flavonoids were the responsible compounds. In V. faba, mature leaves did not respond with a change in epidermal transmittance upon transfer from warm to cool conditions or vice versa, whereas developing leaves did acclimate to the new conditions. We conclude that temperature is an important determinant of the acclimation of epidermal UV transmittance to environmental conditions in many plant species. The potential adaptive value of this response is discussed. PMID- 17277845 TI - [Abstracts of the XXXVIII Annual Meeting of the Genetics Society of Chile, 23-25 November 2005, Puerto Varas, Chile]. PMID- 17277844 TI - [Abstracts of the XLIX annual meeting of the Biology Society of Chile, XXIX annual meeting of the Biochemical and Molecular Biology Society of Chile, XVIII annual meeting of the Botanical Society of Chile, 22-25 November 2006]. PMID- 17277848 TI - [Prognostic factors and outcome of community-acquired pneumonia in hospitalized adult patients]. AB - BACKGROUND: Severity assessment of community-acquired pneumonia (CAP) patients allows the clinician to decide the place of management and guide empirical antimicrobial treatment. AIM: To assess admission prognostic factors and outcome of CAP in immunocompetent adult patients hospitalized in 21 medical centers in Chile. MATERIAL AND METHODS: Prospective evaluation of non immunocompromised adults with CAP admitted to 21 Chilean hospitals between July and August, 1999. All patients were assessed on admission and followed until discharge or death. RESULTS: During the study period, 1,194 patients (aged 68+/-17 years, 573 males) were evaluated. Seventy two percent had an underlying disease (especially chronic cardiovascular, neurological, respiratory diseases and diabetes mellitus), and 90% were treated with beta-lactamic agents (especially a third generation cephalosporin or penicillin). Mean hospital length of stay was 11+/-9 days, 10% were admitted to Intermediate Care or Intensive Care Units (ICU), 6% were mechanically ventilated and in-hospital mortality was 15.7%. Admission prognostic factors associated with hospital mortality were: advanced age, male gender, presence of comorbidity (chronic cardiovascular, renal, neurological and hepatic disease), undernutrition, suspicion of aspiration, altered mental status, low blood pressure, tachypnea, absence of fever, high blood urea nitrogen, multilobar radiographic pulmonary infiltrates, high risk categories from Chilean Respiratory Diseases Society Consensus, admission to Intermediate Care Units or ICU, and mechanical ventilation. In the multivariate analysis, prognostic factors associated with high hospital mortality were: mental confusion, high blood urea nitrogen, multilobar pneumonia, presence of comorbidity and absence of fever on admission. CONCLUSIONS: These results validate in Chile, findings from foreign studies. PMID- 17277849 TI - [Frequency of TEL/AML1 and BCR/ABL fusion genes in children with acute lymphoblastic leukemia]. AB - BACKGROUND: t(12;21) (p12;q22) and t(9;22) (q34;q11) translocations have prognostic significance in acute lymphoblastic leukemia (ALL). The fusion genes TEL/AML1 y BCR/ABL, generated by these translocations, can be easily detected using molecular biology technique. AIM: To study the frequency of TEL/AML1 y BCR/ABL fusion genes in children with ALL. MATERIAL AND METHODS: Fifty-six children with ALL (age range 1 month- 14 years) were studied, thirty-eight from our Temuco Hospital and 18 from the Metropolitan Region. TEL/AML1 y BCR/ABL fusion genes were detected in bone marrow samples using a reverse transcriptase nested polymerase chain reaction (RT-PCR). RESULTS: TEL/AML 1 and BCR/ABL fusion gene transcripts were detected in 13 (23%) and 2 (4%) children, respectively. No differences in survival were observed between children with positive or negative transcripts for TEL/AML1 fusion gene. However, those positive for BCR/ABL fusion gene, had a significantly lower survival. CONCLUSIONS: The frequency of TEL/AML1 and BCR/ABL fusion gene transcripts in these children with ALL is similar to that described by other authors. PMID- 17277850 TI - [Split night polysomnography to titrate continuous positive airway pressure therapy in adult patients with obstructive sleep apnea]. AB - BACKGROUND: Nasal continuous positive airway pressure therapy (CPAP) in the treatment of choice for adult obstructive sleep apnea (OSA). The diagnosis is established with polysomnography, but this study is expensive and must be repeated in those patients that require CPAP, to titrate the pressure of the therapy. Split polysomnography during one night to establish the diagnosis and titrate the pressure has been proposed to reduce costs. AIM: To assess if CPAP pressure can be adequately titrated in patients with OSA using a split-night polysomnography. MATERIAL AND METHODS: One hundred fifty six patients with OSA were studied with split night polysomnography. CPAP pressure titration was considered adequate when there were less than five apnea/hypopnea episodes per hour, the registry time was more than 30 min, REM sleep occurred in more than 15% of the time and measurements were made in supine position. RESULTS: An adequate titration was achieved in 80% of patients. The variables associated with an adequate titration were a higher registry time during the titration period, a higher percentage of stage III/IV or REM sleep during such period and the comfort experienced by the patient during the study. On the other hand, patients with an inadequate titration had a longer basal registry period. CONCLUSIONS: An adequate CPAP pressure can be prescribed to 80% of patients subjected to a split-night polysomnography. The basal registry period should not be longer than three hours, to allow an adequate titration lapse. PMID- 17277851 TI - [One year follow up of successful coronary angioplasty in non selected patients]. AB - BACKGROUND: Re-stenosis after percutaneous coronary angioplasty (PTCA) is related to clinical and angiographic features. AIM: To describe the clinical and angiographic characteristic of our patients with coronary cardiopathy subjected to PTCA and the predictor factors for re-stenosis. MATERIAL AND METHODS: We gathered the clinical and angiographic characteristics of all patients who underwent a successful PTCA of a native coronary artery. All patients had a clinical assessment one year after the procedure. Patients were classified in Group 1, if they did not have angina or coronary events after the angioplasty or Group 2, if they had angina or a coronary event after the procedure. Only Group 2 patients were subjected to a coronary angiogram. RESULTS: We collected 383 PTCA procedures. Follow up information was obtained in 92.2%. Three hundred forty two patients (89.3%) were assessed one year the procedure. Nine patients (2.3%) died of a cardiovascular cause. Ninety patients (26.3%) were classified in Group 2. In 65 patients, angiographic re-stenosis was demonstrated (19%). Re-stenosis occurred in 36 and 13% of patients with an without Diabetes Mellitus, respectively (p <0.01). The other clinical predictor variables were a history of myocardial infarction (p =0.007), obesity (p =0.041) and hypercholesterolemia (p =0.050). None of the angiographic characteristics predicted restenosis. Stents were protective factors against restenosis (15.6% in stented lesions vs 25.4% in nonstented; p =0.01). CONCLUSIONS: Re-stenosis after angioplasty occurred in 19% of our patients with angina or coronary events. The clinical variables associated with a higher risk of re-stenosis were diabetes (the main risk factor), previous myocardial infarction, obesity and hypercholesterolemia. Angiographic variables were not associated with re-stenosis. The use of stents decreases the incidence of re-stenosis in all groups). PMID- 17277852 TI - [Early steroid withdrawal in pediatric renal transplantation]. AB - BACKGROUND: Cardiovascular risk, growth failure and the new immunosuppressive drugs, have encouraged steroid withdrawal or total avoidance with promising results in renal transplant (Tx) immunosuppression. AIM: To evaluate a new immunosuppressor protocol with early withdrawal of steroids in pediatric kidney transplant. PATIENTS AND METHODS: Prospective study in pediatric patients older than 1 year and low immunological risk. Group A (n =28): steroids in decreasing doses until day 7 post Tx, tacrolimus (FK) and mycophenolate mofetil (MMF). Group B (n =28) control: steroids, cyclosporine and azathioprine or steroids, FK and MMF. In both groups the induction therapy included basiliximab. Anthropometric and biochemical variables (renal function, lipid profile, hematological, blood glucose and acid-base equilibrium), acute rejection and CMV infection, were evaluated. Mean values and variations for continuous variables were calculated at months 1, 6, 12 and 18. RESULTS: Two children were withdrawn before month 2, one had an untreatable diarrhea and the second died due to Aspergillus septicemia. Mean values at months 1, 6, 12 and 18 for groups A and B: Creatinine clearance (ml/min): 85.4 vs 89; 79.9 vs 83; 89 vs 80; 79.8 vs 80.6 (p: ns); hematocrit (%): 28.8 vs 30.4; 31.7 vs 34.4; 34.4; 32.4 vs 34.8; 34.4 vs 35.5 (p: ns). Total cholesterol (mg/dl): 151 vs 206; 139 vs 174; 138 vs 186; 140 vs 180 (p <0.05). Mean delta height/age Z score at the first year: 0.5 vs 0.15; 0.7 vs 0.22; 0.97 vs 0.25 (p <0.05). Mean systolic blood pressure Z score: 0.9 vs 1.5; 0.5 vs 0.9; 0.3 vs 0.8; 0.1 vs 1.0 (p <0.05). The height/age Z score was significantly superior in patients without steroids. A normalization of growth patterns at month 18 was observed (< 0.05). Both groups presented a negative variation of creatinine clearance during the follow-up, but it was minor in the study group (p <0.05). Two acute rejections were found in each group, and no difference in CMV infections was observed. CONCLUSIONS: Early steroid withdrawal in pediatric renal transplant recipients was effective and safe and did not increase the risk of rejection. PMID- 17277853 TI - [Evaluation of a stroke unit at a university hospital in Chile]. AB - BACKGROUND: Stroke is the second specific cause of death in Chile, with a mortality rate of 48.6 per 100.000 inhabitants. It accounts for 6% of all hospitalizations among adults. AIM: To study the type of patients hospitalized at a Stroke Unit in a general hospital and the costs and benefits of such unit. MATERIAL AND METHODS: A descriptive and retrospective study using a patient registry, developed in Access that included separate sections for ischemic and hemorrhagic stroke. Established diagnostic criteria were used. The mean costs per patient and complications were also calculated. RESULTS: During 2003, 425 stroke patients were admitted to our hospital and 105 (age range 30-89 years, 58% female) were hospitalized at the Stroke Unit. Eighty-three percent had ischemic and 16% had hemorrhagic stroke. The most common etiologies were thrombosis in 41%, embolism in 36%, lacunar in 13%, arterial dissection in 5% and transient ischemic attack in 3%. Fifty eight percent of patients had partial anterior ischemic stroke (PACI), 73% had hypertension and 29.5% diabetes. Only 18% arrived to the Stroke Unit with less of 6 hours of evolution, 7% of patients were admitted within the 3 hours after the onset of symptoms and 18%, from 3 to 6 hours. The mean length of stay in the Stroke Unit was 6.6 days and at the hospital 9.9 days (p <0.01). The mean costs per patient at the Stroke Unit and at the hospital were US$ 5.550 and US$ 4.815, respectively (p =ns). CONCLUSIONS: The Stroke Unit decreases hospital stay days without raising costs importantly. The inclusion criteria for stroke patients admitted to the Unit were adequate and the stroke registry allowed a good assessment of the Unit operation. PMID- 17277854 TI - [Long term results for intermediate and high grade localized non Hodgkin lymphoma, treated with chemotherapy and radiotherapy]. AB - BACKGROUND: Treatment of intermediate and high grade non-Hodgkin lymphoma (NHL) includes chemotherapy with or without radiotherapy, depending on the clinical stage. The standard treatment for advanced NHL is 8 cycles of combined chemotherapy, cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Patients presenting with localized disease are treated with fewer chemotherapy cycles and involved field radiotherapy, with good results. AIM: To evaluate the treatment results including overall survival (OS) and event-free survival (EFS) in localized aggressive NHL patients treated at the Pontificia Universidad Catolica de Chile, Clinical Hospital. PATIENTS AND METHODS: Retrospective analysis of all patients with Ann Arbor stages I and II referred to the hematology and radiotherapy clinic between 1998 and 2003. OS and EFS analysis was made according to the Kaplan and Meier method. Log-rank and Cox methods were used for univariate and multivariate analyses, respectively. Chemotherapy and radiotherapy toxicities were scored according to World Health Organization (WHO) and Radiation Therapy Oncology Group (RTOG) scales, respectively. RESULTS: 39 patients (20 men), aged between 20 to 85 years, were the source for this study. The average follow-up was 51 months (range 6-115). The 5 years OS and EFS were 72,4% and 63,3%, respectively. On univariate analysis, age over 60 was the only variable that affected negatively OS and EFS. Acute toxicity caused by chemotherapy and radiotherapy was uncommon. CONCLUSIONS: Age over 60 was the only independent variable associated with poor prognosis. The number of chemotherapy cycles and the drug combination did not influence the results. These results support the usefulness of a shortened chemotherapy regimen plus involved field radiotherapy. PMID- 17277856 TI - [Comparison of three brands of intracardiac pacemaker leads]. AB - BACKGROUND: Electrode lead design and materials influence their performance, stability and manipulation characteristics. In our laboratory, we use straight intracardiac, active fixation, steroid eluting leads. These features are shared by three brands of pacemaker distributors. AIM: To compare the short term results of three brands of leads used in our laboratory in patients requiring the implant of a pacemaker or cardioverter. MATERIAL AND METHODS: One hundred and four patients (mean age 70 years, 59 males) subjected to a pacemaker or cardioverter implant were studied and followed during the first three months post implant. In these patients, 49 Guidant Flextend 4087 or 4088, 27 Saint Jude Tendril 1488T and 10 Medtronic Capsurefix 5076 leads were implanted in the right atrium and 60 Guidant Flextend 4087 or 4088, 29 Saint Jude Tendril 1488T and 19 Medtronic Capsurefix 5076 leads were implanted in the right ventricle. RESULTS: Implant parameters were adequate for all leads. A sub-acute rise in ventricular stimulation threshold was detected in one Flextrend lead. Three atrial leads (two Flextend and one Capsurefix) and one Capsurefix ventricular lead experienced an acute displacement. One patient with a Flextend lead, had a cardiac tamponade caused by an atrial perforation. CONCLUSIONS: The three brands of leads tested can be successfully implanted with comparable parameters and without differences in the evolution of patients during the first three months. PMID- 17277855 TI - [Insulin sensitivity in children aged 6 to 16 years: association with nutritional status and pubertal development]. AB - BACKGROUND: There is a high prevalence of obesity and hyperinsulinism among Chilean prepuberal children. AIM: To evaluate insulin sensitivity (IS) using fasting insulin, the Homeostasis Model Assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) in Chilean children. MATERIAL AND METHODS: Body mass index (BMI), total body fat percentage (%TBF) using the sum of 4 skin folds, abdominal obesity determined through waist circumference (WC), pubertal maturation using five Tanner stages, fasting glucose (Glu) and insulin (Ins), were measured in 354 children aged 6 to 15 years (173 males). IS was evaluated using HOMA and QUICKI. RESULTS: IS was strongly associated with %TBF and WC. Ins, HOMA and QUICKI were significantly correlated with BMI (r =0.412; 0.405 y -0.442, respectively), %TBF (r =0.370; 0.367 y -0.394, respectively), and WC (r =0.452; 0.446 y -0.481, respectively). Ins and HOMA increased and QUICKI decreased significantly (p <0.0001) with age. Children in a similar Tanner stage did not have differences in Ins, HOMA and QUICKI. No differences in Ins, HOMA and QUICKI were observed between children in Tanner stages 1 and 2. However, children in Tanner stages 1 and 2, had significantly lower Ins and HOMA and higher QUICKI than those in Tanner 3 to 5 stages. The highest Ins quartile for Tanner stages 1 and 2 was 10.0 micro UI/dl; for Tanner stages 3 to five, the figure was 15.6 microUI/dl. CONCLUSIONS: These results confirm the relationship of IS with BMI, %TBF, WC and pubertal maturation. IS decreases significantly and fasting Ins levels increase approximately 50% with puberty. This fact must be considered for the diagnosis of hyperinsulinism and insulin resistance in children. PMID- 17277857 TI - [McLeod syndrome: Multisystem involvement associated with neuroacanthocytosis linked to X chromosome. report of two related cases]. AB - Neurological abnormalities associated with spiculated, "acanthocytic" red cells in blood have been described as neuroacanthocytosis. This is a heterogeneous group of conditions that can be clearly subdivided on the basis of recent genetic findings. The McLeod Syndrome, one of the core neuroacanthocytosis syndromes, is a rare X-linked disorder caused by mutations of the XK gene, an X-chromosomal gene of unknown function characterized by haemopoietic abnormalities and late onset neurological and muscular defects. We report two Chilean brothers with the McLeod phenotype who showed important psychiatric features. The diagnosis may be elusive if the presence of acanthocytosis is not properly studied. We describe a method which allowed the diagnosis that unmasked acanthocytosis. Otherwise the condition could have remained undiagnosed as it had been for decades in this family. This syndrome must be considered when assessing a familial movement disorder, specially affecting males with relevant psychiatric features. A reliable test for acanthocytosis assessment is available. PMID- 17277858 TI - [Marfan syndrome]. AB - Marfan Syndrome is an autosomic dominant genetic disorder of the elastic fibers of connective tissue. Although neonatal and infant forms of the disease exist, the classic Marfan Syndrome is the most frequent form of presentation in childhood and adolescence, with a hereditary background in 70 to 85% of cases. Due to the natural evolution of the disease, there is a progressive involvement of different organs or systems such as skeletal, cardiovascular, dura, ocular, skin-integument and lungs. However, the suspicion must arise on skeletal clinical aspects which are first evident signs. The cardiovascular involvement appears later but is the major life threatening complication. When suspecting Marfan phenotype, it is mandatory to apply Ghent criteria based on family history and clinical findings to establish the diagnosis. If diagnosis is confirmed, the severity of organ involvement must be assessed, to take preventive and/or therapeutic measures, including the search of new cases among relatives. When patients do not fulfill the diagnostic criteria, they must have a yearly evaluation considering the natural progressive evolution of the disease. The aim of this review is to spread and unify criteria on this disease whose diagnosis is eminently clinical, that requires early integral and updated management by a multidisciplinary group, to obtain the best quality of life and survival. PMID- 17277859 TI - [The possible temporal lobe syndrome of Ivan IV the Terrible]. AB - Ivan IV "The Terrible" was the first Tsar of all Russias and was crowned in 1547. He extended Russian territories and opened the route to Siberia in successful campaigns against Tartars. He increased his personal power to the point of generating an autocracy that isolated him progressively from the council of Boyars. He had a complex personality and his acts were impregnated by a profound religiousness, episodes of rage, mood changes and a sense of "personal fate". All these traits configure the controversial "temporal lobe personality". The possible association between these personality traits and the eventual epilepsy that Ivan IV could suffer, is discussed. This association is called "temporal lobe syndrome". Considering the mood changes, with severe irritability and episodes of control loss alternated with feelings of guilt, sadness and isolation, another possibility is that the Tsar had an affective bipolar disorder or, less probably, a personality disorder. PMID- 17277861 TI - [Cholesterol embolism: report of one case]. AB - We report a 72 year-old male, that after a coronary angiogram presented pain, reduced distal skin temperature of both limbs, cyanosis of toes with preserved peripheral pulses and a rapidly progressive renal failure. Afterwards, the patient suffered a sudden bilateral amblyopia and hematochezia. Cholesterol embolism was confirmed with a skin biopsy and fundoscopy. A colonoscopy showed a possible ischemic colitis. After six months of follow up, the patient lost the distal phalanges of three toes, and renal failure stabilized, with a serum creatinine of 2.5 mg/dl. The diagnosis of cholesterol embolism is often missed, but it has a one year mortality of 80% and the presence of renal failure is the main prognostic indicator. Other prognostic indicators are the presence of high blood pressure, previous renal failure and peripheral artery disease. PMID- 17277862 TI - [On medical professionalism]. PMID- 17277863 TI - [Gastrointestinal stromal tumours (GIST)]. PMID- 17277864 TI - [Biological and psychosocial factors that predict health promoting lifestyles]. AB - BACKGROUND: One of the goals of the national health reform is to promote a healthy lifestyle in all the population. The determinants of healthy lifestyles need to be identified to guide people towards this purpose. AIM: To analyze the health promoting lifestyle (HLP) in a community of Concepcion and to identify the personal factors that might be predictors of such lifestyle. MATERIAL AND METHODS: Pender's health promotion model was used as the conceptual framework for exploring the HLP among 360 persons aged from 15 to 64 years, free from chronic diseases. Data were obtained by a semi structured questionnaire and the following scales were used to measure HLP: perceived health status, perceived self esteem, and perceived self efficacy. Relationships between personal factors and HLP were studied. Data were processed with SAS software and analyzed with descriptive and inferential statistics. RESULTS: Only 52.2% of the sample had a healthy lifestyle. The variables sex, age, occupation, access to health care, self esteem, perceived health status and perceived self efficacy had a significant effect on HLP. A regression model showed that self esteem, self efficacy, sex, age, occupation and access to health care explained 30% of the variation in health lifestyle. CONCLUSIONS: Only half of the studied sample had a healthy lifestyle. The variables obtained with the regression model, should be considered to create effective interventions encouraging persons to integrate healthy behaviors to their life. PMID- 17277865 TI - [Knowledge about their disease and treatment among patients with rheumatoid arthritis]. AB - BACKGROUND: The transfer of information in the physician-patient relationship is important, especially in chronic diseases such as Rheumatoid Arthritis (RA), since it influences the perception and behavior that the patient has about his or her illness. AIM: To evaluate the level of knowledge and concern of their illness and treatment and their relationship with functional disability, perception of the pain and global assessment of disease activity, in patients with RA. PATIENTS AND METHODS: Cross sectional study of 104 patients (mean age 56 years, 100 women) with RA. Demographic and clinical variables were registered. The knowledge about their illness and requirement of further information and concern about aspects of the illness and treatment, were assessed. Physical functioning was measured using the Health Assessment Questionnaire (HAQ). A visual analogue (VAS) and Likert scales were used for a global assessment of disease activity. RESULTS: Sixty percent of patients had only primary school studies. The median evolution of the illness was 14 years. Ninety eight percent knew their diagnosis and 91% required further information. There was a high degree of concern about the disease and treatment. The average HAQ score was 0.9. There was a statistically significant relationship between HAQ score and pain VAS (r =0.41, p <0.01). There was a moderate agreement between the global assessment of disease activity made by patients and physicians (Kappa =0.499; p =0.000). CONCLUSIONS: Even though patients with RA are informed about their disease, they require further information. Their highest concern is about the functional consequences of RA and they perceive a higher activity of the disease than their treating physicians. PMID- 17277866 TI - [Intensified insulin therapy plus antineuritic medication is more effective than antineuritics alone in painful diabetic neuropathy]. AB - BACKGROUND: The basis of the treatment of painful diabetic neuropathy is the use of drugs that block the transmission of pain (antineuritics) and a good metabolic control of underlying disease. AIM: To describe the outcomes of 17 type-2 diabetics with painful neuropathy, treated between 1988 and 2005 with symptomatic therapy plus intensified insulin. MATERIAL AND METHODS: Review of medical records of 17 type-2 diabetic patients, aged 63+/-11 years and a duration of diabetes of 15+/-8 years. All patients received intensified insulin therapy with 0.35 units/kg of NPH insulin (2/3 before breakfast and 1/3 evening meal), plus capillary glucose measurements and regular insulin (with sliding-scale centered in approximately 0.1 units/kg) before the 3 main meals. All patients were also treated with gabapentin, nortriptyline or clomipramine. Pain was assessed using a visual analog score of 10 points. RESULTS: After 1 year, glycosilated hemoglobin decreased from 10.0+/-1.4% to 7.7+/-1.2% (p approximately =0.003). Pain decreased from 10 to 5.1+/-3.3 at one month, 2.3+/-3.2 at six months, and 3.1+/-3.6 at 1 year (p <0.01). There was a direct statistical correlation between the reduction of HbA1C and pain decline (r =0.736; p =0.037). Pain scores were lower than those reported elsewhere for Pregabalin (n =76; p =0.05), Lamotrigine (n =27; p <0.0005), Topiramate (n =208; p <0.005), and Gabapentin (n =84; p <0.025). The lack of difference to Sodium Valproate (n =21; p =0.07) had borderline significance. CONCLUSIONS: The addition of intensified insulin therapy to the symptomatic treatment of painful neuropathy in type-2 diabetics, significantly enhanced the reduction of pain. The lowering of glycosilated hemoglobin was a significant predictor of success in pain reduction. PMID- 17277867 TI - [Perception of abuse among medical students of the University of Chile]. AB - BACKGROUND: Even though studying Medicine and perceiving abuse seem to be two opposite situations, recent investigations in Chile and abroad find that this is a frequent and pervasive combination. These studies also report the negative effects in the lives of students as well as the impact on the profession as a whole. AIM: To ascertain the perception of abusive situations in medical students during training at the University of Chile. MATERIAL AND METHODS: Descriptive and cross sectional study in which a questionnaire was applied to all the students enrolled in 2nd, 3rd, 5th and 7th year during 2001 and 2002. Using short vignettes, they were asked if they had experienced verbal, psychological, physical and sexual abuse, at least once, during their training, by whom and the eventual effects derived from it. RESULTS: We obtained 757 questionnaires. Of the surveyed students, 91% reported having perceived at least one abusive episode during training. Teachers and fellow students were identified as the main offenders. Among the effects of such behavior, 32% mentioned that they considered dropping out of the career as a consequence of this experience. DISCUSSION: The perception of abuse in medical students is common and has adverse effects. Efforts should be made to draw attention to this problem to prevent it. PMID- 17277868 TI - [Rectal barostat in irritable bowel syndrome]. AB - BACKGROUND: Many patients with irritable bowel syndrome (IBS) have lowered sensory thresholds to rectal distention when compared to control subjects, a phenomenon called visceral hypersensitivity. AIM: To investigate the usefulness of a rectal barostat as a diagnostic tool in IBS and if there are differences in visceral hypersensitivity in different groups of IBS patients. PATIENTS AND METHODS: Ten healthy subjects and 19 IBS patients, defined using Rome II criteria (12 with constipation, three with diarrhea and four alternating between diarrhea and constipation), were studied. Sequential isobaric rectal distentions, from 2 mmHg up to a maximal pressure of 52 mmHg or when the patients reported pain, were carried out. Visceral hypersensitivity was defined as a pain threshold under 38 mmHg. RESULTS: Only 26% of IBS patients had visceral hypersensitivity (16% and 43% of patients with IBS and constipation and IBS and diarrhea or alternating symptoms, respectively, p =NS). Pain threshold in controls, patients with IBS and constipation and patients with IBS and diarrhea or alternating symptoms was 43.8+/-6.6, 45.3+/-9.2 and 40.8+/-9.2 mmHg, respectively (p =NS). CONCLUSIONS: Our results do not support the usefulness of the electronic rectal barostat as a diagnostic method to diagnose IBS. PMID- 17277869 TI - [Adverse reactions to L-asparaginase in children with acute lymphatic leukemia]. AB - BACKGROUND: The low notification of Adverse Drug Reactions (ADR) underscores the need for pharmacological surveillance systems that allow their detection, evaluation, prevention and registry especially in patients receiving multiple medications. AIM: To communicate the ADR observed with the use E coli asparaginase (E coli ASP) in children with Acute Lymphatic Leukemia (ALL). PATIENTS AND METHODS: Cross-sectional study of clinical records of all the patients aged less than 15 years with ALL (n =52) and treated between January 1996 and April 2000. The suspicion of ADR to E coli ASP was evaluated using the Karch and Lasagna algorithm. Probable and definitive cases of ADR to E coli ASP were subjected to a protocol of clinical and epidemiological data. The risk factors associated to ADR to E coli ASP, were also determined. RESULTS: Fifty children aged 1 to 13 years (33 men) were studied. In 20 (40%), an ADR to E coli ASP, was suspected. After the use of the algorithm, the ADR was considered definite in two patients, probable in 17 and possible in one. The registered clinical events were urticaria in 17, anaphylactic shock in four, transient alterations of hepatic functions test in seven and hypofibrinogenemia in four. The test of cutaneous sensitivity to the administration of E coli ASP, performed prior to the administration of the drug, were positive in nine of the 20 children with adverse reactions. No children died. CONCLUSIONS: The application of the Karch anbd Lasagna algorithm, allowed us to objectively classify suspected cases of ADR by E coli ASP. PMID- 17277870 TI - [Clinical picture at the onset of type 1 diabetes mellitus in children]. AB - BACKGROUND: Type 1 diabetes mellitus (DM1) is a disease of increasing incidence among children. The time elapsed between the beginning of symptoms and the diagnosis of the disease is, in most cases, very extended. AIM: To report the clinical picture at onset and laboratory features of children with DM1. MATERIAL AND METHODS: Retrospective review of all medical records of patients admitted to the hospital with a DM1 of recent onset. RESULTS: Sixty three males aged 95+/-47 months and 34 females aged 109+/-51 months, were studied. Males were significantly younger than females (p <0.05). The lapse between symptoms onset and the diagnosis of the disease was longer in girls than in boys (46+/-46 and 26+/-26 days respectively, p <0.02). There was an inverse correlation between plasma glucose and the lapse between symptoms onset and the diagnosis of disease. The most common clinical picture of the disease was the classical symptoms of diabetes (polyuria, polydipsia, weight loss), in 60% of cases. Thirty seven percent had developed ketoacidosis at the time of the diagnosis. Ketoacidosis was more common between 1988 and 1995, as compared with the period 1996-2003 (50% and 28.8%, respectively). The onset of symptoms occurred between April and August (Winter in the Southern Hemisphere) in 38% of cases. CONCLUSIONS: DM1 is a disease of increasing incidence among children, whose diagnosis is delayed, even though symptoms are evident. The lower incidence of ketoacidosis in our patients between 1996 and 2003 is encouraging. PMID- 17277871 TI - [Genetic studies of a Chilean family with three different dental anomalies]. AB - BACKGROUND: Congenital dental anomalies can affect up to 25% of the population. AIM: To report the genetic study of a family with dental anomalies. MATERIAL AND METHODS: We studied a Chilean family presenting with three independent dental phenotypes: third molar agenesis, supernumerary teeth, and dentinal dysplasia type I. We searched for mutations in candidate genes proposed for tooth agenesis and supernumerary teeth: IRF6, FGFR1, MSX1, MSX2, PAX9, PRDM16 and TGFA. We also studied DSPP as a candidate gene for dentinal dysplasia type I. RESULTS: We did not find mutations in FGFR1, MSX2, PAX9, PRDM16, or TGFA. We found a MSX1 mutation (G16D) in both affected and unaffected family members. Also, we found a genetic variation not described before in IRF6 in the dentinal dysplasia type I case. CONCLUSIONS: Further investigation is necessary to evaluate if these variants are functional in nature. Finally, we are reporting a mutation in DSPP in an asymptomatic 2-year-old child, which illustrates the ethical pitfalls of interpreting molecular data for genetic counseling of young and/or asymtomatic individuals. PMID- 17277872 TI - [Increasing rates of Down syndrome among newborns in Chile from 1972 to 2005]. AB - BACKGROUND: There are some records shrowing that the frequency of Down syndrome is experiencing an increase over time. AIM: To verify whether the frequency of Down syndrome is increasing in the maternity of the University of Chile Clinical Hospital, or in other Chilean hospitals participating in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) and compare the rates with other world registries of congenital malformations. MATERIAL AND METHODS: The information was obtained from the ECLAMC databases of the maternity. The Down syndrome incidence rates were calculated from 1997 to 2005 and rate curves were constructed. RESULTS: The overall rate of Down syndrome was 3.36 per 10,000 born alive. This rate experienced a significant increase in the study period. These rates differ in the different Chilean regions, being higher in Santiago and lower in the Southern regions of the country. The mean age of mothers of newborns with or without Down syndrome was 36+/-6 and 29+/-6 years, respectively, p >0.001. CONCLUSIONS: The rates of newborns with Down syndrome increased in the period 1972-2005, bearing a close relationship with the increase in maternal ages. PMID- 17277873 TI - [Tumor necrosis factor receptor associated periodic syndrome (TRAPS). Report of two cases]. AB - Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is an autoinflammatory disorder associated to a mutation of the Tumor Necrosis Factor Receptor 1 (TNFR1) whose clinical presentation consists on recurrent episodes of prolonged fever, abdominal pain, myalgias, migratory cutaneous erythema, conjunctivitis or periorbitary edema. The diagnosis is confirmed by genetic analysis of the TNFR1 gene. Its main complication is amyloidosis and the treatment is based on the use of corticosteroids or anti-TNF antibodies. We report a 17 year-old male and 23 year-old female with the syndrome. Both cases had heterozygous mutations of the TNFR1 gene, C30R in the first case and T50M in the second case. PMID- 17277874 TI - [Anisakiasis in a patient with a small hiatal hernia. Report of one case]. AB - We describe the presence of anisakiasis in a patient who had a small hiatal hernia. A 60 year-old women presented general malaise, burning pain, flatulence, persistent nausea and abdominal distension during five days before consulting. She referred that she ate a dish of marinated raw fish with lemon and pepper ("cebiche") and after a few hours the symptoms began. An esophagogastroscopy showed a white colour larva of approximately three cm with the cephalic end partially adhered and localized in the mucosa of the hiatal hernia. During the procedure the worm was easily extracted. The morphologic study of the specimen identified it as a stage IV larva of Pseudoterranova sp. The clinical condition of the patient improved after the extraction of the parasite. PMID- 17277875 TI - [Panic attacks in a patient treated with isotretinoin for acne. Report of one case]. AB - The use of isotretinoin as a treatment for acne is related to psychiatric syndromes such as psychosis and depression. On the other hand, several drugs have been identified as causing panic attacks. A relationship between dermatologic and psychiatric disease has also been established. We report a 20 year-old male who started to suffer panic attacks after using isotretinoin for acne. PMID- 17277876 TI - [Ambulatory management of community acquired pneumonia in the elderly]. AB - Community Acquired Pneumonia (CAP) is the first cause of death by respiratory disease in Chile and the first specific cause of death in people over 80 years of age. The geriatric population has a greater risk of suffering pneumonia, its complications and consequently dying. This is not only related to chronological age but also to certain factors related to ageing such as the presence of comorbidity, malnutrition, and cognitive impairment. An atypical presentation that delays the diagnosis and treatment also increases the risk of complications. CAP in the elderly is caused by the same pathogens that cause it in younger patients. S pneumoniae is the main pathogen followed by viral infections particularly in winter. An important strategy to reduce CAP related health costs, is the identification of patients who are at low risk of complications and who therefore could be managed at home. Optimum management of CAP in the elderly includes early diagnosis and the definition of clinical severity, early antibiotic treatment at the right dose and for an adequate length of time and a correct decision whether the patient should be managed in hospital or at home. PMID- 17277877 TI - [Conflicts of interest in clinical practice. Ethical analysis of some relationships with the pharmaceutical industry]. AB - Sometimes, the prescription practice of physicians can be influenced by factors that are not related to scientific evidence due to the appearance of several conflicts of interest. These conflicts cause social concern and have prompted actions to regulate the ethics of individual and corporative activities related to healthcare. We analyzed the ethical problems involved in the physician industry relationship. For this purpose, we considered as the main actors related to this problem, the pharmaceutical industry and their marketing strategies, medical doctors and the independence and objectivity that should guide prescriptions and, finally, patients and their right to receive prescriptions based on scientific evidence. From the point of view of the Bioethics principles, Beneficence would not be respected when gifts or other donations received from the industry affect doctor's independence. Non Maleficence principle could be jeopardized if there is an increased risk of treatment failure and finally Justice could be altered if there is a cost increase for either patients or health institutions. As a conclusion, we consider that the presence of conflicts of interest in the relationship of physicians with the pharmaceutical industry is an important ethical problem. In consequence, this group endorses the recommendations of the Chilean Association of Medical Scientific Societies and advices to include ethical guidelines on this topic in the curriculum of medical schools. PMID- 17277878 TI - [Interchangeability of biological drugs: considerations about the approval of biogeneric formulations in Chile]. AB - Once drug patents expire, the health authorities can approve the registry of similar products. They must request to the manufacturer, the bibliographic background of the original product and the analytical results that certify drug quality. An inspection of the premises of the manufacturer is also required. The main goal of this approval is to decrease cost, considering that the original product is usually more expensive. This is a current situation due to the imminent expiration of the patents of many biopharmaceutical products. Therefore, in Chile, the Public Health (ISP) and the Ministry of Health should consider that for this kind of products, until now, there are no interchangeable generic drugs, and that the similar drugs that are offered have a different chemical composition, since they have been manufactured through different processes. In the case of biological drugs (e.g. erythropoietir, somatotropin, heparin) the quality and homogeneity depend from the manufacture process. Its complete composition can not be absolutely elucidated; therefore small impurities or conformational variants can elicit an altered immune response or unexpected adverse reactions. This indicates that the approval of a biogeneric drug requires in addition to pharmacokinetic studies, preclinical and clinical analytical studies such as physicochemical assays, biological and immunological test. This issues have been established by WHO and have been incorporated for the main drug registry entities all over the world (FDA, EMEA, ANVISA) to approve biogeneric products. PMID- 17277879 TI - [Subacute combined degeneration of the spinal cord caused by vitamin B12 deficiency]. PMID- 17277880 TI - [Palliative Care for renal patients]. PMID- 17277881 TI - Current perspectives on histone demethylases. AB - The posttranslational modification of histones plays an important role in chromatin regulation. Histone methylation influences constitutive heterochromatin, genomic imprinting, X-chromosome inactivation and gene transcription. Histone demethylase catalyzes the removal of methyl groups on lysine or arginine residues of histones. Two kinds of histone lysine demethylases have been identified, including lysine specific demethylase 1 and Jumonji C (JmjC) domain family proteins. These histone demethylases are involved in the regulation of gene expression. Histone modification is a dynamic process, and the imbalance of histone methylation has been linked to cancers. Therefore, histone demethylases may represent a new target for anti-cancer therapy. PMID- 17277883 TI - Tolerance of mice to lipopolysaccharide is correlated with inhibition of caspase 3-mediated apoptosis in mouse liver cells. AB - Bacterial endotoxin lipopolysaccharide (LPS) often results in multiple organ failure. However, pre-exposure of mice to a sublethal dose of LPS renders the animal tolerant to a lethal dose of LPS. This study was designed to determine whether pre-exposure of a small dose of LPS was able to suppress apoptosis in mice when challenged with LPS in combination with D-galactosamine, and to investigate the expression changes of the apoptosis-associated molecules. The results showed that a characteristic apoptotic DNA fragmentation existed in mouse livers of the LPS-naive group, but not in control groups; and the mice of the LPS naive group were all dead after 2 d. However, in the LPS-tolerance groups, both the lethal rate and apoptotic DNA fragmentation were suppressed after the mice were challenged with LPS/D-galactosamine, and the protection against the lethality and apoptotic reaction could be maintained for up to 7 d. In this period, significantly lower levels of caspase-3 and its mRNA appeared in LPS tolerant groups compared to those of the LPS-naive group (P<0.05), and the caspase-3 activities gradually recovered as the observation was prolonged. Our findings suggest that LPS tolerance could suppress apoptosis in mouse liver cells, and the expression and activity of caspase-3 could be down-regulated. PMID- 17277882 TI - Triptolide inhibits cyclooxygenase-2 and inducible nitric oxide synthase expression in human colon cancer and leukemia cells. AB - Triptolide (TP), a traditional Chinese medicine, has been reported to be effective in the treatment of autoimmune diseases and exerting antineoplastic activity in several human tumor cell lines. This study investigates the antitumor effect of TP in human colon cancer cells (SW114) and myelocytic leukemia (K562), and elucidates the possible molecular mechanism involved. SW114 and K562 cells were treated with different doses of TP (0, 5, 10, 20, or 50 ng/ml). The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Results demonstrated that TP inhibited the proliferation of both tumor cell lines in a dose-dependent manner. To further investigate its mechanisms, the products prostaglandin E(2) (PGE(2)) and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay (ELISA). Our data showed that TP strongly inhibited the production of NO and PGE(2). Consistent with these results, the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX 2) was up-regulated both at the mRNA level and the protein expression level, as shown by real-time RT-PCR and Western blotting. These results indicated that the inhibition of the inflammatory factor COX-2 and iNOS activity could be involved in the antitumor mechanisms of TP. PMID- 17277884 TI - Cloning, sequencing and expression analysis of the first cellulase gene encoding cellobiohydrolase 1 from a cold-adaptive Penicillium chrysogenum FS010. AB - A cellobiohydrolase 1 gene (cbh1) was cloned from Penicillium chrysogenum FS010 by a modified thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR). DNA sequencing shows that cbh1 has an open reading frame of 1590 bp, encoding a putative protein of 529 amino acid residues. The deduced amino acid sequence revealed that CBHI has a modular structure with a predicted molecular mass of 56 kDa and consists of a fungal type carbohydrate binding module separated from a catalytic domain by a threonine rich linker region. The putative gene product is homologous to fungal cellobiohydrolases in Family 7 of the glycosyl hydrolases. A novel cbh1 promoter (1.3 kb) was also cloned and sequenced, which contains seven putative binding sites (5'-SYGGRG-3') for the carbon catabolite repressor CRE1. Effect of various carbon sources to the cbh1 transcription of P. chrysogenum was examined by Northern analysis, suggesting that the expression of cbh1 is regulated at transcriptional level. The cbh1 gene in cold-adaptive fungus P. chysogenum was expressed as an active enzyme in Saccharomyces cerevisiae H158. The recombinant CBHI accumulated intracellularly and could not be secreted into the medium. PMID- 17277885 TI - TRAF3 interacts with Smac/DIABLO and enhances the proapoptotic effect of Smac/DIABLO in cytoplasm. AB - Smac/DIABLO (second mitochondria-derived activator of caspase/direct IAP-binding protein with low PI) is a 29 kDa mitochondrial precursor protein, which is proteolytically processed in mitochondria into a 23 kDa mature protein. It is released from the mitochondrial intermembrane space to cytosol after an apoptotic trigger. Smac/DIABLO acts as a dimer and it contributes to caspase activation by sequestering the inhibitor of apoptosis proteins (IAPs). In order to further investigate the mechanism of Smac/DIABLO action, we used the mature form of Smac/DIABLO as a bait and screened proteins that interact with mature Smac/DIABLO in human liver cDNA library using the yeast two-hybrid system. Forty-two colonies were obtained after 5.8x10(6) colonies were screened by nutrition limitation and X-galactosidase assay. After DNA sequence analysis and homology retrieval, one of the candidate proteins was identified as TRAF domain of the TNF receptor associated factor 3 (TRAF3). The interaction site between TRAF3 and Smac/DIABLO was identified by beta-galactosidase test. The interaction between TRAF3 and Smac/DIABLO via TRAF domain was identified in vivo by co-immunoprecipitation in HepG2 cells, and the direct interaction between TRAF3 and Smac/DIABLO in vitro was identified by GST-pull down assay. Co-expression of TRAF3 and mature Smac/DIABLO in 293 cells could enhance the Smac/DIABLO-mediated apoptosis. These results suggested that TRAF3 interacted with Smac/DIABLO via TRAF domain, leading to an increased proapoptotic effect of Smac/DIABLO in cytoplasm. PMID- 17277886 TI - Comparison of transformation efficiency of piggyBac transposon among three different silkworm Bombyx mori Strains. AB - The transformation rate of three different strains of silkworm Bombyx mori was compared after the introduction of enhanced green fluorescence protein (EGFP) encoding genes into the silkworm eggs by microinjection of a mixture of piggyBac vector and helper plasmid containing a transposase-encoding sequence. Although there were no significant differences among the three strains in the percentages of fertile moths in microinjected eggs (P=0.1258), the percentages of G(0) transformed moths in fertile moths and injected eggs were both significantly different (P=0.01368 and P=0.02398, respectively). The transformation rate of the Nistari strain (Indian strain) was significantly higher than that of the other two strains, Golden-yellow-cocoon (Vietnamese strain) and Jiaqiu (Chinese strain), which had similar rate. These results indicate that the transformation efficiency of the piggyBac-based system might vary with silkworm strains with different genetic backgrounds. The presence of endogenous piggyBac-like elements might be an important factor influencing the transformation efficiency of introduced piggyBac-derived vectors, and the diverse amount and activation in different silkworm strains might account for the significant differences. PMID- 17277888 TI - Adiponectin decreases plasma glucose and improves insulin sensitivity in diabetic Swine. AB - To investigate the effects of recombinant human adiponectin on the metabolism of diabetic swine induced by feeding a high-fat/high-sucrose diet (HFSD), diabetic animal models were constructed by feeding swine with HFSD for 6 months. The effects of recombinant adiponectin were assessed by detecting the change of plasma glucose levels by commercially available enzymatic method test kits and evaluating the insulin sensitivity by oral glucose tolerance test (OGTT). About 1.5 g purified recombinant adiponectin was produced using a 15-liter fermenter. A single injection of purified recombinant human adiponectin to diabetic swine led to a 2- to 3-fold elevation in circulating adiponectin, which triggered a transient decrease in basal glucose level (P<0.05). This effect on glucose was not associated with an increase in insulin level. Moreover, after adiponectin injection, swine also showed improved insulin sensitivity compared with the control (P<0.05). Adiponectin might have the potential to be a glucose-lowering agent for metabolic disease. Adiponectin as a potent insulin enhancer linking adipose tissue and glucose metabolism could be useful to treat insulin resistance. PMID- 17277887 TI - Protective effects of vitamin E against oxidative damage induced by Abeta1 40Cu(II) complexes. AB - beta-amyloid peptide (Abeta) is considered to be responsible for the formation of senile plaques, which is the hallmark of Alzheimer's disease (AD). Oxidative stress, manifested by protein oxidation and lipid peroxidation, among other alterations, is a characteristic of AD brain. A growing body of evidence has been presented in support of Abeta(1-40) forming an oligomeric complex that binds copper at a CuZn superoxide dismutase-like binding site. Abeta(1-40)Cu(II) complexes generate neurotoxic hydrogen peroxide (H(2)O(2)) from O(2) via Cu(2+) reduction, though the precise reaction mechanism is unclear. The toxicity of Abeta(1-40) or the Abeta(1-40)Cu(II) complexes to cultured primary cortical neurons was partially attenuated when (+)-alpha-tocopherol (vitamin E) as free radical antioxidant was added at a concentration of 100 mM. The data derived from lactate dehydrogenase (LDH) release and the formation of H(2)O(2) confirmed the results from the MTT assay. These findings indicate that copper binding to Abeta(1-40) can give rise to greater production of H(2)O(2), which leads to a breakdown in the integrity of the plasma membrane and subsequent neuronal death. Groups treated with vitamin E exhibited much slighter damage, suggesting that vitamin E plays a key role in protecting neuronal cells from dysfunction or death. PMID- 17277889 TI - Suppression of type 1 Insulin-like growth factor receptor expression by small interfering RNA inhibits A549 human lung cancer cell invasion in vitro and metastasis in xenograft nude mice. AB - Cancer invasion and metastasis, involving a variety of pathological processes and cytophysiological changes, contribute to the high mortality of lung cancer. The type 1 insulin-like growth factor receptor (IGF-1R), associated with cancer progression and invasion, is a potential anti-invasion and anti-metastasis target in lung cancer. To inhibit the invasive properties of lung cancer cells, we successfully down-regulated IGF-1R gene expression in A549 human lung cancer cells by small interfering RNA (siRNA) technology, and evaluated its effects on invasion-related gene expression, tumor cell in vitro invasion, and metastasis in xenograft nude mice. A549 cells transfected with a plasmid expressing hairpin siRNA for IGF-1R showed a significantly decreased IGF-1R expression at the mRNA level as well as the protein level. In biological assays, transfected A549 cells showed a significant reduction of cell-matrix adhesion, migration and invasion. Consistent with these results, we found that down-regulation of IGR-1R concomitantly accompanied by a large reduction in invasion-related gene expressions, including MMP-2, MMP-9, u-PA, and IGF-1R specific downstream p-Akt. Direct tail vein injections of plasmid expressing hairpin siRNA for IGF-1R significantly inhibited the formation of lung metastases in nude mice. Our results showed the therapeutic potential of siRNA as a method for gene therapy in inhibiting lung cancer invasion and metastasis. PMID- 17277890 TI - Purification and characterization of cytosolic glyceraldehyde-3-phosphate dehydrogenase from the dromedary camel. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12), a key enzyme of carbon metabolism, was purified and characterized to homogeneity from skeletal muscle of Camelus dromedarius. The protein was purified approximately 26.8 folds by conventional ammonium sulphate fractionation followed by Blue Sepharose CL-6B chromatography, and its physical and kinetic properties were investigated. The native protein is a homotetramer with an apparent molecular weight of approximately 146 kDa. Isoelectric focusing analysis showed the presence of only one GAPDH isoform with an isoelectric point of 7.2. The optimum pH of the purified enzyme was 7.8. Studies on the effect of temperature on enzyme activity revealed an optimal value of approximately 28-32 degrees with activation energy of 4.9 kcal/mol. The apparent K(m) values for NAD(+) and DL-glyceraldehyde-3 phophate were estimated to be 0.025+/-0.040 mM and 0.21+/-0.08 mM, respectively. The V(max) of the purified protein was estimated to be 52.7+/-5.9 U/mg. These kinetic parameter values were different from those described previously, reflecting protein differences between species. PMID- 17277891 TI - The use of magnesium in bronchial asthma: a new approach to an old problem. AB - Magnesium deficiency is a common electrolyte disorder in patients with acute severe asthma, but intracellular magnesium content better reflects its homeostasis than does its serum concentration. Magnesium takes part in many metabolic processes in the organism, including energy metabolism, protein and nucleic acid synthesis, cell cycle, the binding of substances to the plasma membrane, and maintenance of cytoskeletal and mitochondrial integrity. It also modulates ion transport and influences intracellular calcium concentration. Maintenance of the cells' transmembrane gradient depends on the presence of magnesium, and hypomagnesemia may result in an increase in neuromuscular cell excitability. Magnesium is a cation modulating the smooth muscle contractility of different tissues: hypomagnesemia causes their contraction and hypermagnesemia their relaxation. Suggestions of a positive influence of magnesium in the treatment of asthma exacerbation have been known for a long time, but research results differ. A single dose of intravenous magnesium sulfate given to patients with acute asthma exacerbation has been shown to be safe, but its efficiency is still under discussion. According to the Global Initiative for Asthma GINA-2005, magnesium sulfate administration is not recommended for routine treatment, but it is permitted in patients with severe asthma exacerbation not responding to treatment (evidence category A). Recommendations of the British Thoracic Society allow one dose of magnesium sulfate to patients with acute severe asthma exacerbation and inadequate initial response to broncho-dilating inhalation treatment (evidence category A). Future investigations should help to establish the indications for magnesium use in the treatment of acute asthma exacerbations as well as the magnesium dose and the scheme of its administration. PMID- 17277893 TI - Antichlamydial antibodies and citric acid in patients with chronic prostatitis. AB - INTRODUCTION: The aim of the study was to evaluate the correlation between the presence of anti-C. trachomatis (C.t.) antibodies in serum and expressed prostatic secretions (EPS) and the concentration of citric acid in patients with chronic prostatitis. MATERIALS AND METHODS: The study involved 34 men with chronic prostatitis. The leukocyte count, presence of anti-C.t. antibodies (IgA, IgG), and citric acid concentration were determined in the EPS. The serum was examined for IgM, IgA, and IgG anti-C.t. antibodies. Specific antibodies were determined using the EIA method. The concentration of citric acid was measured using the ultraviolet method. RESULTS: Inflammation of the prostate (210 PMN) was found in 61.8% of the patients. A reduction in citric acid concentration in the EPS was detected in 58.8% of the men. Specific serum antibodies were detected in 58.8% of the patients, including 23.5% with IgM, 32.4% with IgA, and 44.1% with IgG. In all patients, serum IgM and IgA antibody titers were low, while those of IgG antibodies were strongly positive in 46.7% of the patients. Anti-C.t. antibodies in the EPS were detected in 44.1% of the patients, including 32.4% with IgA and 35.3% with IgG. In contrast to serum, the titers of IgG antibodies in the EPS were low in all the patients, while those of IgA were strongly positive in 54.5% of cases. In patients with positive serological outcomes, 85% had reduced concentrations of citric acid. CONCLUSIONS: The occurrence of anti C.t. antibodies is usually accompanied by a decrease in the concentration of citric acid in the prostatic secretion. PMID- 17277892 TI - Transcriptional regulation in thymic epithelial cells for the establishment of self tolerance. AB - Thymic epithelial cells (TECs) play pivotal roles in the establishment of self tolerance through critical dialogue with developing thymocytes. Unique actions of two transcriptional regulators within TECs, NF-kappaB-inducing kinase (NIK) and an autoimmune regulator (AIRE), for the establishment of self tolerance have recently been highlighted by studies using a strain of mouse bearing a natural mutation of the NIK gene (aly mice) and gene-targeted mice, respectively. Previous studies have demonstrated essential roles of NIK downstream of the lymphotoxin-beta receptor (LTbetaR), which is essential for the development of secondary lymphoid organs; aly mice lack all lymph nodes and Peyer's patches because of the defective LTbetaR signaling. Additional roles of NIK in thymic organogenesis downstream of LTPR, mainly through the developmental regulation of TECs, have now emerged, although the corresponding ligand(s) for LTbetaR participating in this action have not been fully characterized. In contrast, AIRE, a gene responsible for the development of an organ-specific autoimmune disease that demonstrates monogenic autosomal recessive inheritance, contributes to the establishment of self tolerance probably by controlling the expression of self antigens through yet undetermined molecular mechanisms. Thus, it is highly likely that a group of genes control self tolerance within TECs through unique and coordinated actions, and that an understanding of this process would help to unravel the pathogenesis of autoimmune disease. PMID- 17277894 TI - Peroxisome proliferator-activated receptor gamma (PPAR gamma) and sepsis. AB - This review describes the role of the nuclear hormone receptor PPARgamma as a double-edged sword in sepsis. On the one hand, PPARgamma inhibits pro inflammatory gene expression, predominantly by scavenging transcription factors and their cofactors, thus preventing them from binding to their cognate binding sites in the promoters of target genes. The expressions of the affected genes, such as those for inducible nitric oxide synthase, TNF-alpha, or IL-1beta, are repressed. Therefore, PPARgamma is suggested to be beneficial in hyper inflammatory diseases, such as sepsis. In animal models of sepsis, PPARgamma agonist pretreatment auspiciously attenuated inflammation compared with control animals, accompanied by their improved survival rate. On the other hand, PPARgamma provokes apoptosis, which in the hyper-inflammatory phase of sepsis might be helpful because the number of immune cells, such as monocytes, macrophages, and neutrophils, involved in secreting high amounts of proinflammatory mediators will be reduced. In contrast, during the anti inflammatory phase, cell death of immune cells, especially of T lymphocytes, is supposed to be deleterious. Under these circumstances, a second infection cannot be adequately answered, thus causing septic shock and multi-organ dysfunction syndrome. Therefore the role of PPARgamma is still ambiguous. Particularly its role in initiating apoptosis awaits further clarification to finally elucidate its impact on sepsis development. PMID- 17277895 TI - Immunological system status and the appearance of respiratory system disturbances in thymectomized patients. AB - INTRODUCTION: Adult-onset thymoma may be responsible for several diseases, such as pure red cell aplasia, myasthenia gravis, and immunodeficiency (Good's syndrome). Thymectomy does not always improve the patient's condition, and may even produce additional symptoms. Its pathogenesis is still not entirely understood, but autoimmunological processes and bone marrow defect are the most frequently suggested. MATERIALS AND METHODS: Eleven patients (mean age: 56.2+/ 15.5 years) were analyzed 6 months to 10 years after thymectomy due to thymoma as were 25 healthy persons serving as controls. Enzyme-linked immunosorbent assay (ELISA) and flow cytometry techniques were used to evaluate the immunological status of the subjects. RESULTS: Good's syndrome was diagnosed in one patient, 4 subjects suffered from myasthenia gravis, and recurrent infections of upper and lower respiratory tract appeared in 9 patients. The immunological analyses (ELISA and flow cytometry) revealed a significantly lower IgG level (p<0.05), percentage of peripheral blood B lymphocytes (p<0.0005), and CD4:CD8 ratio (p<0.05) in thymectomized patients compared with the healthy controls. The percentages of CD4+ and CD8+ T lymphocytes expressing CD28 antigen were significantly lower in thymectomized patients than in healthy subjects (p<0.005 and p<0.01, respectively). The percentage of naive T helper lymphocytes was significantly lower in the patients than in the control group (p<0.05). CONCLUSIONS: Immunodeficiency and recurrent infections may be the first symptoms of immunological disturbances after thymectomy in adults. It is suggested that regular medical monitoring of these patients is important in preventing further complications, which may result in irreversible lung tissue destruction. PMID- 17277897 TI - A biogeochemical framework for metal detoxification in sulfidic systems. AB - We develop a comprehensive biogeochemical framework for understanding and quantitatively evaluating metals bio-protection in sulfidic microbial systems. We implement the biogeochemical framework in CCBATCH by expanding its chemical equilibrium and biological sub-models for surface complexation and the formation of soluble and solid products, respectively. We apply the expanded CCBATCH to understand the relative importance of the various key ligands of sulfidic systems in Zn detoxification. Our biogeochemical analysis emphasizes the relative importance of sulfide over other microbial products in Zn detoxification, because the sulfide yield is an order of magnitude higher than that of other microbial products, while its reactivity toward metals also is highest. In particular, metal-titration simulations using the expanded CCBATCH in a batch mode illustrate how sulfide detoxifies Zn, controlling its speciation as long as total sulfide is greater than added Zn. Only in the absence of sulfide does complexation of Zn to biogenic organic ligands play a role in detoxification. Our biogeochemical analysis conveys fundamental insight on the potential of the key ligands of sulfidic systems to effect Zn detoxification. Sulfide stands out for its reactivity and prevalence in sulfidic systems. PMID- 17277898 TI - Expression and phylogenetic analyses of human endogenous retrovirus HC2 belonging to the HERV-T family in human tissues and cancer cells. AB - Recently, a new HERV-T family, representative of the HERV-S71 and HERV-HC2 family, was identified using a screen for envelope genes and a computer-assisted database search. Here, we investigate expression of pol fragments of HERV-HC2 belonging to the HERV-T family in various human tissues and cancer cells. The pol gene was expressed in nearly all human tissues examined and in all cancer cell lines. Expression analyses suggest that the pol gene of HERV-HC2 family is more actively transcribed in human cancer cells than in normal tissues, suggesting a functional role during carcinogenesis. Phylogenetic analysis of the HERV-HC2 pol family revealed three groups (I, II, and III) generated through evolutionary divergence during primate evolution, indicating that they were integrated into primate genomes approximately 56 million years (MY) ago and have evolved at a rate of 0.2% nucleotide differences per MY. Our data might contribute to an understanding of the information on the transcriptional and pathological potential of the HERV-T family in human disease, including cancer. PMID- 17277899 TI - Polymorphic Alu insertions and the genetic structure of Iberian Basques. AB - Eight Alu sequences (ACE, TPA25, PV92, APO, FXIIIB, D1, A25 and B65) were analyzed in two samples from Navarre and Guipuzcoa provinces (Basque Country, Spain). Alu data for other European, Caucasus and North African populations were compiled from the literature for comparison purposes to assess the genetic relationships of the Basques in a broader geographic context. Results of both MDS plot and AMOVA revealed spatial heterogeneity among these three population clusters clearly defined by geography. On the contrary, no substantial genetic heterogeneity was found between the Basque samples, or between Basques and other Europeans (excluding Caucasus populations). Moreover, the genetic information obtained from Alu data conflicts with hypotheses linking the origin of Basques with populations from North Africa (Berbers) or from the Caucasus region (Georgia). In order to explain the reduced genetic heterogeneity detected by Alu insertions among Basque subpopulations, values of the Wright's F(ST )statistic were estimated for both Alu markers and a set of short tandem repeats (STRs) in terms of two geographical scales: (1) the Basque Country, (2) Europe (including Basques). In the Basque area, estimates of Wahlund's effect for both genetic markers showed no statistical difference between Basque subpopulations. However, when this analysis was performed on a European scale, F(ST) values were significantly higher for Alu insertions than for STR alleles. From these results, we suggest that the spatial heterogeneity of the Basque gene pool identified in previous polymorphism studies is relatively recent and probably caused by a differential process of genetic admixture with non-Basque neighboring populations modulated by the effect of a linguistic barrier to random mating. PMID- 17277896 TI - IBR3, a novel peroxisomal acyl-CoA dehydrogenase-like protein required for indole 3-butyric acid response. AB - Indole-3-butyric acid (IBA) is an endogenous auxin that acts in Arabidopsis primarily via its conversion to the principal auxin indole-3-acetic acid (IAA). Genetic and biochemical evidence indicates that this conversion is similar to peroxisomal fatty acid beta-oxidation, but the specific enzymes catalyzing IBA beta-oxidation have not been identified. We identified an IBA-response mutant (ibr3) with decreased responses to the inhibitory effects of IBA on root elongation or the stimulatory effects of IBA on lateral root formation. However, ibr3 mutants respond normally to other forms of auxin, including IAA. The mutant seedlings germinate and develop normally, even in the absence of sucrose, suggesting that fatty acid beta-oxidation is unaffected. Additionally, double mutants between ibr3 and acx3, which is defective in an acyl-CoA oxidase acting in fatty acid beta-oxidation, have enhanced IBA resistance, consistent with a distinct role for IBR3. Positional cloning revealed that IBR3 encodes a putative acyl-CoA dehydrogenase with a consensus peroxisomal targeting signal. Based on the singular defect of this mutant in responding to IBA, we propose that IBR3 may act directly in the oxidation of IBA to IAA. PMID- 17277900 TI - Anthocyaninless1 gene of Arabidopsis thaliana encodes a UDP-glucose:flavonoid-3-O glucosyltransferase. AB - We isolated several mutants of Arabidopsis thaliana (L.) Heynh. that accumulated less anthocyanin in the plant tissues, but had seeds with a brown color similar to the wild-type. These mutants were allelic with the anthocyaninless1 (anl1) mutant that has been mapped at 15.0 cM of chromosome 5. We performed fine mapping of the anl1 locus and determined that ANL1 is located between the nga106 marker and a marker corresponding to the MKP11 clone. About 70 genes are located between these two markers, including three UDP-glucose:flavonoid-3-O-glucosyltransferase like genes and a glutathione transferase gene (TT19). A mutant of one of the glucosyltransferase genes (At5g17050) was unable to complement the anl1 phenotype, showing that the ANL1 gene encodes UDP-glucose:flavonoid-3-O glucosyltransferase. ANL1 was expressed in all tissues examined, including rosette leaves, stems, flower buds and roots. ANL1 was not regulated by TTG1. PMID- 17277901 TI - Enhancement of cytotoxicity against Vero E6 cells persistently infected with SARS CoV by Mycoplasma fermentans. AB - We previously reported that cells with persistent severe acute respiratory syndrome coronavirus (SARS-CoV) infection were established after apoptotic events. In the present study, we investigated the cytopathic effects of dual infection with SARS-CoV and Mycoplasma fermentans on Vero E6 cells. Dual infection completely killed cells and prevented the establishment of persistent SARS-CoV infection. M. fermentans induced inhibition of cell proliferation, but the cells remained alive. Apoptosis was induced easily in M. fermentans-infected cells, indicating that they were primed for apoptosis. These results indicated that M. fermentans enhances apoptosis in surviving cells that have escaped from SARS-CoV-induced apoptosis. PMID- 17277902 TI - Detection strategies of tick-borne encephalitis virus in Swedish Ixodes ricinus reveal evolutionary characteristics of emerging tick-borne flaviviruses. AB - The flaviviral tick-borne encephalitis virus (TBEV) is a human pathogen having significant impact on public health. The geographical distribution of TBEV and TBEV-like viruses is increasing, which makes it important to characterise the natural virus populations. Here we present four RT-PCR strategies designed for detection of broad types of tick-borne flaviviruses. Sequence information on more than 32% of a TBEV genome was generated from a small pool of ticks collected in the Stockholm archipelago on the island of Toro. The sequences were characterised and compared with those of other tick-borne flaviviruses, which classified the virus as Western European TBEV. PMID- 17277903 TI - A chlorophyll c2 analogue from the marine brown alga Eisenia bicyclis inactivates the infectious hematopoietic necrosis virus, a fish rhabdovirus. AB - We screened in vitro antiviral activity against a salmonid pathogenic virus, infectious hematopoietic necrosis virus (IHNV), from the extracts of a total of 342 species of marine algae collected from the Japanese coastline. The anti-IHNV activity was found primarily in MeOH extracts, and the extract from one marine brown alga in particular, Eisenia bicyclis, showed high anti-IHNV activity. The anti-IHNV compound was isolated and purified as MC15 from the E. bicyclis extract, and the chemical structure was determined by several spectrometric analyses. The antiviral compound was proved to be a chlorophyll c2 derivative lacking the metal ion Mg(2+). MC15 showed similar antiviral activity against other salmonid enveloped viruses such as Paralichthys olivaceus virus and Oncorhynchus masou virus, and stability against any pH and temperatures up to 100 degrees C. No cytotoxicity was observed at up to 5 microg/ml. The antiviral mechanism of MC15 appears to be direct inactivation of the viral particles. A time course study showed that the inactivation of IHNV was completed within 40 min when 200 PFU of IHNV was reacted with MC15 at 800 ng/ml. PMID- 17277904 TI - Implantation of a distractible titanium cage after cervical corpectomy: technical experience in 20 consecutive cases, by M. Payer, Volume 148, Issue 11, November 2006, Pages 1173-1180. PMID- 17277907 TI - Characterization of Aeromonas virulence using an immunocompromised mouse model. AB - An immunocompromised mouse model was used to characterize Aeromonas strains for their ability to cause opportunistic, extraintestinal infections. A total of 34 isolates of Aeromonas (A. hydrophila [n = 12]), A. veronii biotype sobria [n = 7], A. caviae [n = 4], A. enchelia [n = 4], A. allosaccharophila [n = 2], A. salmonicida (n = 4), and A. bestiarum [n = 1]) were introduced by intraperitoneal injection into immunocompetent or chemically compromised (using cyclophosphamide) mice. The ability of each isolate to persist in the liver and spleen tissue was monitored at 24 hours after exposure. A majority ofA. hydrophila and A veronii v. sobria strains, but none of the isolates of other Aeromonas species, were capable of persistent colonization (<300 cells/mg spleen and liver tissue at 24 hours). The presence or absence of several putative virulence factors (cytotoxicity to HEp-2, lipase activity, elastase activity, and hemolysis) were determined for each isolate using in vitro tests. There were no correlations between the presence or absence of biochemical test results for putative virulence factors and persistence of the isolate in spleen and liver tissue at 24 hours. PMID- 17277908 TI - Inhibition of cyanide-insensitive respiration in Klebsiella oxytoca SYSU-011 by 8 hydroxyquinolone. AB - The inhibition of the cyanide (KCN)-insensitive respiration of Klebsiella oxytoca SYSU-011 by 8-hydroxyquinoline (8-HQ) was determined. Results showed that the profile of the rate of oxygen uptake of normal-grown and 8-HQ-grown K. oxytoca SYSU-011 was biphasic and similar, suggesting that 8-HQ did not inhibit the respiration of normal-grown K. oxytoca SYSU-011. A different biphasic KCN inhibition profile of respiration was observed for KCN-grown cells treated with and without 8-HQ. No decrease in respiration rate of KCN-grown cells and a 40% decrease in respiration rate of KCN-grown cells treated with 8-HQ were observed when KCN concentration was 10(-1) mM. Comparing differences of the profiles of oxygen uptake in KCN-grown cells with and without 8-HQ addition indicated that 8 HQ inhibited expression of the KCN-insensitive pathway carried out by nonheme oxidase. Greater inhibition of NADH oxidase activity by 2-n-heptyl-4 hydroxyquinoline-N-oxide from the cell membrane of the KCN-grown cells treated with 8-HQ, and more H2O2 production from these cells with than without 8-HQ, suggest that the function of the cyanide-insensitive pathway can stabilize the respiration of the cyanide-grown cells to prevent the production of H2O2. PMID- 17277909 TI - Acute confusional state following a whiplash injury: a case of multiple cervical artery dissection. PMID- 17277910 TI - A study of subtle blood brain barrier disruption in a placebo-controlled trial of natalizumab in relapsing remitting multiple sclerosis. AB - Natalizumab, an anti-alpha4 integrin antibody, significantly reduces the number of visibly enhancing multiple sclerosis (MS) lesions. In this substudy of a 2 year trial of natalizumab monotherapy versus placebo, contrast-enhanced imaging investigated for subtle blood brain barrier (BBB) leakage in relapsing remitting (RRMS) patients, and whether such leakage is modified by natalizumab. After 24 weeks on treatment, 40 patients from 3 centres (27 on natalizumab and 13 on placebo) were studied. T1 weighted images were obtained before and at set timepoints up to 46 minutes after gadolinium (Gd)-DTPA (0.3 mmol/kg to 18 patients, 0.15 mmol/kg to 22). Paired regions of interest were placed around non enhancing lesions and contralateral normal appearing white matter (NAWM). BBB leakage was inferred through post-Gd T1 weighted signal intensity (SI) change. SI change was greater in T2 non-enhancing lesions than paired NAWM at all timepoints (P<0.005), indicating BBB leakage in lesions. No significant difference in inferred BBB leakage was observed between treatment arms as measured by SI change of lesions (P>0.05 for all timepoints, joint test P=0.24), or in SI change of NAWM (joint test P=0.37). T1 hypointense and isointense lesions exhibited similar SI changes (joint test P=0.12). There is evidence of a subtle BBB leakage within visibly non-enhancing lesions in RRMS that was not modified by alpha4 integrin blockade in this substudy cohort. PMID- 17277911 TI - Reboxetine improves motor function in chronic stroke. A pilot study. AB - Animal experiments have indicated that noradrenergic agents can improve the recovery from stroke. In this double-blind placebo-controlled crossover study, hemiparetic chronic stroke patients (n = 10) received a single dose of the noradrenaline reuptake inhibitor reboxetine or placebo. Then the patients participated in one hour of physiotherapy focused on function of the paretic hand. Three different motor assessments (tapping speed, grip strength, dexterity evaluation) were performed before drug intake, 1.5 hours later and after the physiotherapy session. Transcranial magnetic stimulation (TMS) was used to investigate motor excitability by measuring motor thresholds and amplitudes of motor evoked potentials. Both hands were studied. Compared with placebo, reboxetine ingestion was followed by an increase of tapping speed and grip strength in the paretic but not in the unaffected hand. No further improvement was noticed after physiotherapy. TMS results and dexterity measurements remained unchanged. We conclude that reboxetine improved simple hand functions in chronic stroke patients. Reboxetine should be considered as an additional tool in neurorehabilitation. PMID- 17277913 TI - Expression of vascular endothelial growth factor by plasma cells in the sclerotic bone lesion of a patient with POEMS syndrome. PMID- 17277912 TI - Tau missing from CSF: a case report. PMID- 17277914 TI - The "enhanced N35" somatosensory evoked potential: its associations and potential utility in the clinical evaluation of dystonia and myoclonus. AB - In median nerve somatosensory evoked potentials, the cortical N35 amplitude sometimes exceeds the P25 amplitude (C3'/C4' referred to Fz; "enhanced N35" feature). Six hundred consecutive patient median nerve SEPs were retrospectively analysed and compared with 27 controls. The feature was more often present in patients with dystonia (62%) than in patients with other disorders (22%; relative risk for the condition 2.8; Fisher's exact p=0.003) or control subjects (7.4%; odds ratio 20; p=0.0006). Similarly, the feature was more often present in patients with myoclonus (38%) than in patients with other disorders (22%; relative risk 1.7; p=0.02) or control subjects (odds ratio 7.5; p=0.006). There was no clear relationship of the feature to short latency SEP abnormalities except in cases of myoclonus. Further comparison was made of the characteristics of 72 patients each, with and without the feature, whose short latency SEP components were normal. The relationship of the feature to dystonia or myoclonus held true in this case-controlled arm of the study. The sensitivity and specificity were 65% and 78% respectively for any form of dystonia; 43% and 79% respectively for any form of myoclonus. The feature was even more specific in both conditions when compared with controls (93%). Most cases of dystonia with an identifiable cause in this study were of secondary forms. It is known that this feature often occurs in association with "giant" SEPs in some myoclonic conditions. However, its occurrence in dystonia may be a useful new finding in an established test, helping to identify a condition where there is increasing evidence for disordered sensorimotor integration. PMID- 17277917 TI - Management of floating knee. PMID- 17277918 TI - [Therapeutic strategies for chronic constipation in childhood: pediatric gastroenterological and surgical aspects]. AB - Chronic constipation in childhood results from (1) psychological/behavioural causes, (2) functional or organic gastrointestinal outlet obstruction, or (3) slowing of transit within the colon. Functional chronic constipation is treated by a complex conservative bowel management. Constipation refractory to routine medical treatment reveals, in a significant number of cases, organic causes. Histology of bowel biopsies is essential for the preoperative diagnosis of chronic constipation. Defective innervated bowel segments require surgical treatment. Intraoperative histological staining of bowel biopsies allows proper resection of aganglionic or dysganglionic bowel. This contribution describes the interdisciplinary, clinicopathological interactions involving children with chronic constipation. PMID- 17277919 TI - [Hypoganglionosis as a cause of chronic constipation]. AB - Hypoganglionosis comprises 3-5% of gastrointestinal innervation defects which are connected to therapy-resistant chronic constipation in children and adults. Similar to Hirschsprung's disease, hypoganglionosis may be complicated by megacolon formation and must be considered in the differential diagnosis. Three main subtypes may be distinguished: congenital hypoplastic hypoganglionosis occurs predominantly in Hirschsprung's disease proximal to the aganglionic segment and consists of small paucicellular ganglia with increased interganglionic distances. Oligoneuronal dysganglionic hypoganglionosis manifests in childhood. Initially, myenteric ganglia are of normal size and have normal interganglionic spacing and normal neuronal content. However, nerve cells are hypoplastic and ganglia undergo progressive nerve cell loss. This type of hypoganglionosis may progress into atrophic hypoganglionosis, which shows a morphology similar to hypoplastic hypoganglionosis. All subtypes of hypoganglionosis result in decreased acetylcholinesterase activity in the nerve fiber network of the muscularis propria. The pathogenesis of hypoganglionosis is still poorly understood. In Hirschsprung associated hypoganglionosis, mutations in the RET and GDNF-genes have been found. Despite a heterozygote GDNF+/- animal model for hypoganglionosis, no GDNF mutations have so far been demonstrated in human Hirschsprung independent, isolated hypoganglionosis. PMID- 17277920 TI - [Stem cells of the enteric nervous system: causal therapy for Hirschsprung's disease?]. AB - Stem cells are self-renewing cells with the potential to generate different cell types. The human organism depends on stem cells for organ development during embryogenesis. Upon completion of organogenesis, stem cells are also necessary for organ maintenance ("homeostasis") and for tissue regeneration. In view of the manifold functions of stem cells, it is not surprising that their malfunction results in diseases like Hirschsprung's disease, a disorder of the enteric nervous system of complex etiology. Potential stem cell application for the regeneration of diseased organs, such as the enteric nervous system in Hirschsprung's disease, is currently a focus of intense research. PMID- 17277921 TI - ATP signaling site in the ARM domain of atrial natriuretic factor receptor guanylate cyclase. AB - Atrial natriuretic factor (ANF) receptor guanylate cyclase (ANF-RGC) is a single transmembrane spanning modular protein. It binds ANF to its extracellular module and activates its intracellular catalytic module located at its carboxyl end. This results in the accelerated production of cyclic GMP, which acts as a critical second messenger in decreasing blood pressure. Two mechanistic models have been proposed for the ANF signaling of ANF-RGC. One is ATP-dependent and the other ATP-independent. In the former, ATP works through the ARM (ATP-regulated transduction module) of ANF-RGC. This model has recently been challenged [Antos et al. (2005) J Biol Chem 280:26928-26932] in support of the ATP-independent model. The present in-depth study analyzes the major principles of this challenge and concludes that the challenge lacks merit. The study then moves on to dissect the ATP mechanism of ANF signaling of ANF-RGC. It shows that the ATP photoaffinity probe, [gamma(32)P]-8-azido-ATP, reacts with Cys(634) residue in the ATP-binding pocket of ARM, and also signals the ANF-dependent activation of ANF-RGC. The target site of the 8-azido (nitrene) group is between the Cys(634) and Val(635) bond of the ATP-binding pocket. Thus, the study experimentally validates the ARM model-predicted role of Val(635) in the folding pattern of the ATP-binding pocket. And, it also identifies another residue Cys(634) that along with eight already identified residues is a part of the fold around the adenine ring of the ATP pocket. This information establishes the direct role of ATP in ANF signal transduction model of ANF-RGC, and provides a significant advancement on the mechanism by which the ATP-dependent transduction model operates. PMID- 17277922 TI - The importance of a clean face: the effect of different washing procedures on the association of Tamm-Horsfall glycoprotein and other urinary proteins with calcium oxalate crystals. AB - This study was undertaken to determine whether the use of different washing procedures could explain dissident findings in published studies examining the role of urinary macromolecules in urolithiasis. Calcium oxalate monohydrate (COM) crystals were deposited from or added to the same sieved urine, washed with copious or limited amounts of distilled water, or with methanol, and examined by field emission scanning electron microscopy (FESEM). Demineralized extracts were analysed by SDS-PAGE and Western blotting for Tamm-Horsfall glycoprotein (THG), human serum albumin (HSA), osteopontin (OPN) and prothrombin fragment 1 (PTF1). Synchrotron X-ray diffraction (SXRD) with Rietveld whole-pattern peak fitting and profile analysis was used to determine non-uniform crystal strain and crystallite size in crystals generated from inorganic solutions in the presence of increasing concentrations of THG and prothrombin (PT). HSA and PTF1 were present in all demineralized crystal extracts, confirming their inclusion within COM. OPN was present in all extracts except those derived from pure inorganic COM crystals, because of its occlusion within small numbers of calcium oxalate dihydrate (COD) crystals contaminating the COM population. THG was absent from the demineralized extracts of all crystals washed copiously with water, but present in those washed with methanol or limited amounts of water. FESEM showed extraneous organic material associated only with crystals whose extracts contained THG, confirming that the protein does not bind permanently to the COM crystal surface and is not occluded within the mineral bulk. This was confirmed by SXRD, which showed that non-uniform strain and crystallite size remained unaltered in crystals grown in the presence of increasing THG concentrations. However, non-uniform strain increased and crystallite size decreased with increasing PT concentrations, demonstrating unambiguously that PT is included in COM crystals. It was concluded that scrupulous care must be taken to ensure the complete removal of extraneous THG adventitiously associated with CaOx crystals in order to avoid inaccurate analysis of crystal matrix protein content and possible misinterpretation of experimental data. PMID- 17277923 TI - Balloon kyphoplasty in the management of vertebral compression fractures: an updated systematic review and meta-analysis. AB - This systematic review updates the understanding of the evidence base for balloon kyphoplasty (BKP) in the management of vertebral compression fractures. Detailed searches of a number of electronic databases were performed from March to April 2006. Citation searches of included studies were undertaken and no language restrictions were applied. All controlled and uncontrolled studies were included with the exception of case reports. Prognostic factors responsible for pain relief and cement leakage were examined using meta-regression. Combined with previous evidence, a total of eight comparative studies (three against conventional medical therapy and five against vertebroplasty) and 35 case series were identified. The majority of studies were undertaken in older women with osteoporotic vertebral compression fractures with long-term pain that was refractory to medical treatment. In direct comparison to conventional medical management, patients undergoing BKP experienced superior improvements in pain, functionality, vertebral height and kyphotic angle at least up to 3-years postprocedure. Reductions in pain with BKP appeared to be greatest in patients with newer fractures. Uncontrolled studies suggest gains in health-related quality of life at 6 and 12-months following BKP. Although associated with a finite level of cement leakage, serious adverse events appear to be rare. Osteoporotic vertebral compression fractures appear to be associated with a higher level of cement leakage following BKP than non-osteoporotic vertebral compression fractures. In conclusion, there are now prospective studies of low bias, with follow-up of 12 months or more, which demonstrate balloon kyphoplasty to be more effective than medical management of osteoporotic vertebral compression fractures and as least as effective as vertebroplasty. Results from ongoing RCTs will provide further information in the near future. PMID- 17277924 TI - End-of-life care for nursing home residents dying from cancer in Nova Scotia, Canada, 2000-2003. AB - INTRODUCTION: With our population aging, an increasing proportion of cancer deaths will occur in nursing homes, yet little is known about their end-of-life care. This paper identifies associations between residing in a nursing home and end-of-life palliative cancer care, controlling for demographic factors. METHODS: For this population-based study, a data file was created by linking individual level data from the Nova Scotia Cancer Centre Oncology Patient Information System, Vital Statistics, and the Halifax and Cape Breton Palliative Care Programs for all persons 65 years and over dying of cancer from 2000 to 2003. Multivariate logistic regression was used to compare nursing home residents to nonresidents. RESULTS: Among the 7,587 subjects, 1,008 (13.3%) were nursing home residents. Nursing home residents were more likely to be female [adjusted odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2-1.7], older (for > or = 90 vs 65 69 years OR 5.4, CI 4.1-7.0), rural (OR 1.5, CI 1.2-1.8), have only a death certificate cancer diagnosis (OR 4.2, CI 2.8-6.3), and die out of hospital (OR 8.5, CI 7.2-10.0). Nursing home residents were less likely to receive palliative radiation (OR 0.6, CI 0.4-0.7), medical oncology consultation (OR 0.2, CI 0.1 0.4), and palliative care program enrollment (Halifax OR 0.2, CI 0.2-0.3; Cape Breton OR 0.4, CI 0.3-0.7). CONCLUSION: Demographic characteristics and end-of life services differ between those residing and those not residing in nursing homes. These inequalities may or may not reflect inequities in access to quality end-of-life care. PMID- 17277925 TI - Critical weight loss in head and neck cancer--prevalence and risk factors at diagnosis: an explorative study. AB - GOALS OF WORK: Critical weight loss (> or =5% in 1 month or > or =10% in 6 months) is a common phenomenon in head and neck cancer patients. It is unknown which complaints are most strongly related to critical weight loss in head and neck cancer patients at the time of diagnosis. The aim of this explorative study was to assess the prevalence of critical weight loss and to analyze risk factors for critical weight loss in head and neck cancer patients before treatment. MATERIALS AND METHODS: Critical weight loss and factors reducing dietary intake were assessed in 447 patients referred to an ear, nose and throat clinic at the time of diagnosis. MAIN RESULTS: In total, data of 407 patients were analyzed. Critical weight loss was present in 19% of the patients. Patients with cancer in the hypopharynx, oropharynx/oral cavity and supraglottic larynx had the highest risk for critical weight loss. Loss of appetite, dysphagia/passage difficulties and loss of taste/aversion were significantly (p < 0.05) associated with critical weight loss. CONCLUSIONS: Already before treatment, critical weight loss is a considerable problem in head and neck cancer patients. Critical weight loss is frequently observed in patients with cancer in the hypopharynx, oropharynx/oral cavity and supraglottic larynx. PMID- 17277926 TI - Speed of haemoglobin response in patients with cancer: a review of the erythropoietic proteins. AB - BACKGROUND: Patients with cancer-related anaemia generally have a poor prognosis. Evidence suggests that an effective erythropoietic protein (epoetin)-mediated haemoglobin (Hb) response provides marked improvement in quality of life (QoL). An early Hb response to erythropoietic protein therapy in these patients would appear ideal but few studies have compared the speed of response to different erythropoietic proteins, or the potential benefits associated with an early Hb response. RESULTS AND DISCUSSION: The pharmacokinetic/pharmacodynamic profiles of commercially available erythropoietic proteins are reviewed along with available clinical data to examine Hb response and associated clinical outcomes for each of these agents. Randomised, head-to-head trials comparing epoetin alfa and darbepoetin alfa suggest that patients administered with epoetin alfa achieve a satisfactory Hb response significantly earlier than those given darbepoetin alfa, and with consistently lower monthly transfusion rates. Non-comparative studies support this, suggesting also that epoetin beta may provide a relatively faster Hb response in a greater number of patients than either epoetin alfa or darbepoetin alfa, irrespective of malignancy or chemotherapy type. Moreover, studies suggest consistently that a 'front-loading' dosing regimen with epoetin alfa does not convey improved speed of Hb response over epoetin beta administered according to current clinical practice guidelines. CONCLUSIONS: Given the poor prognosis of anaemic patients with cancer, the use of an agent which provides clinical benefits quickly but with minimal thromboembolic risk, should be considered an essential component of anaemia management in these patients. However, more head-to-head studies are required to confirm the relative efficacy of currently available erythropoietic proteins. PMID- 17277927 TI - The interplay of pollination, costs of reproduction and plant size in maternal fertility limitation in perennial Paeonia officinalis. AB - Although several factors can limit female fertility in perennial plants, rarely have they been jointly studied in a single species over several years. In this study we experimentally manipulate seed production and simultaneously analyse the potential contribution of pollen limitation, costs of reproduction and plant size to variation in seed output over a 3-year period in the perennial herb Paeonia officinalis, in southern France. Since this rare species is threatened by forest closure in many sites we also examine the causes of female fertility variation in relation to habitat closure (open habitat vs. woodland). P. officinalis has a partial self-incompatibility system and only very low ability for autonomous self pollination in the absence of pollinators. However, supplementary pollination of individual plants in three consecutive years did not significantly increase seed production above natural levels. Forest closure was associated with a decline in ovule and seed production, which again was not due to pollen limitation since supplementary pollination had no significant effect on seed set in the woodland habitat. Comparison of the maternal fertility of plants which were previously excluded from reproduction with those which were hand pollinated to maximise seed set in two previous years produced no evidence that seed production in year three is limited by costs associated with prior reproduction. Likewise, flowering probability was not related to prior seed production but was however positively related to plant size. The absence of any influence of pollen limitation or prior reproduction on seed production suggests that sub-maximal seed production in long lived perennial herbs may be part of a size-dependent strategy that maximises life-time seed production and fitness without compromising survival. PMID- 17277928 TI - Extreme weather change and the dynamics of oviposition behavior in the pipevine swallowtail, Battus philenor. AB - Prospects of global increases in extreme weather change provide incentive to examine how such change influences animal behavior, for example, behavior associated with resource use. In this study, we examined how oviposition behavior in a southern Arizona population of pipevine swallowtails (Battus philenor L.) responded to changes in their Aristolochia host resource and vegetative background caused by the North American monsoon system. Summer monsoon rains resulted in a flush of non-host vegetation and a more than doubling in rate of landings by host-searching females on non-host vegetation. Rates of discovery of the host species A. watsoni Woot. Standl. decreased by 50% after monsoon rains. Rains did not alter host density appreciably, but resulted in significant increases in host plant size and new growth, two indicators of host suitability for B. philenor larvae. After the rains, mean clutch size on individual host plants increased by a factor of 2.5; the mean proportion of host plants encountered on which a female laid eggs also increased significantly. Females were discriminating about the host plants on which they laid eggs after alightment; plants accepted for oviposition were larger, bore more new growth, and bore fewer larvae than rejected plants. Contrary to predictions from foraging theory, degree of discrimination did not change seasonally. Finally, the rate at which eggs were laid increased seasonally, suggesting that oviposition rates were limited more before monsoon rains by the relatively low quality of hosts than they were after the rains by the relatively low rate at which hosts were found. This latter result suggests that, while butterflies possess behavioral flexibility to respond to extreme weather change, such flexibility may have limits. In particular, expected increases in the severity and frequency of droughts may result in reduced oviposition rates, reductions that could have adverse demographic consequences. PMID- 17277929 TI - Population cycles and changes in body size of the lynx in Alaska. AB - The lynx Lynx canadensis is a common predator in the boreal forests of North America. Its population fluctuates during a 9- to 11-year cycle in synchrony with the population size of its main prey, the snowshoe hare Lepus americanus. Using adult museum specimens, we studied changes in skull (and hence body) size of the lynx in Alaska during the second half of the 20th century. The population cycle in Alaska averaged 9 years, similar to that reported in the neighbouring Yukon. Using harvest data of lynx as an estimate of population size, we found that skull size was negatively related to population size. This relationship was strongest not for the population density in the year of death (X), but for year X-3, a carry-over effect from the first year (or years) of life, indicating that conditions during the fast-growth years are determining body size. We suggest that the density-dependent effect is probably due to changes in food supply, either resulting from the adverse effects of competition or a possible diminished availability of food. Two skull parameters decreased significantly during the second half of the 20th century. We do not know the cause for the year effect and suggest that it might be due to a long-term change in the availability of prey. Canine size did not change during the study period, probably an indication that snowshoe hares maintained their status as the main prey of the lynx throughout the study period. PMID- 17277930 TI - Form and performance: body shape and prey-capture success in four drift-feeding minnows. AB - Identifying links between morphology and performance for ecologically relevant tasks will help elucidate the relationships between organismal design and fitness. We conducted a laboratory study to quantify the relationship between variation in body shape and prey-capture success in four drift-feeding minnow species. We offered drifting prey to individual fish in a test flume, counted successful strikes to measure prey-capture success and recorded the position (X, Y coordinates) of ten landmarks on each fish's outline to delineate the specimen's form. We then quantified shape variation among species and related it to capture performance through thin-plate spline analysis. Body shape varied significantly among species and with specimen size and was the major determinant of capture success, explaining 45-47% of its variability. Prey-capture success at differing velocities differed among species, but once the effects of shape and size were accounted for, those differences were no longer significant. Allometric shape changes appeared responsible for most of the ontogenetic variation in capture performance, although other size-related, non-shape factors also seemed relevant. Fishes with deeper, shorter bodies, more caudally placed median fins and larger, more upward-pointing mouths exhibited greater capture success than more fusiform fish, suggesting that streamlining, which is energetically advantageous for sustained swimming, entails a cost in terms of prey-capture ability. Our findings demonstrate a strong connection between organismal shape and performance and provide empirical evidence of the cost of morphological specialization for fishes in the drift-feeding functional guild. PMID- 17277931 TI - Immuno-PET of undifferentiated thyroid carcinoma with radioiodine-labelled antibody cMAb U36: application to antibody tumour uptake studies. AB - PURPOSE: We tested the suitability of the chimeric monoclonal anti-human CD44 splice version 6 antibody (cMAb U36) for targeting and visualising human anaplastic thyroid carcinoma with PET. We also performed experiments aimed at elucidating the relation between tumour interstitial fluid pressure (TIFP) and the tumour uptake of antibodies. METHODS: The affinity and specificity of the cMAb U36 for KAT-4 cells were evaluated in vitro, as was the Na+/I- symporter (NIS) expression. Biodistribution studies were performed on KAT-4 carcinoma bearing mice injected with 124I-cMAb U36 or free iodine. Biodistribution studies were also performed in animals treated with the specific TGF-beta1 and -beta3 inhibitor Fc:TbetaRII, which lowers TIFP. Treated and non-treated animals were scanned by microPET. RESULTS: Cultured human undifferentiated/anaplastic thyroid carcinoma KAT-4 cells expressed low levels of NIS and uptake of free iodine was insignificant. The cMAb U36 expressed an affinity (KD) of 11+/-2 nM. Tumour radioactivity uptake reached maximum values 48 h after injection of 124I-cMAb U36 (approximately 22%IA/g). KAT-4 carcinomas were readily identified in all 124I immuno-PET images. Radioactivity tumour uptake in Fc:TbetaRII-treated animals was significantly lower at 24 and 48 h after injection, and five times higher thyroid uptake was also noted. CONCLUSION: We successfully used 124I-cMAb U36 to visualise CD44v6-expressing human anaplastic thyroid carcinoma. Given the lack of NIS expression in KAT-4, tumour visualisation is not due to free iodine uptake. Lowering the TIFP in KAT-4 carcinomas did not increase the uptake of mAbs into tumour tissue. PMID- 17277932 TI - The calcium-sensing protein synaptotagmin 7 is expressed on different endosomal compartments in endocrine, neuroendocrine cells or neurons but not on large dense core vesicles. AB - Synaptotagmin (syt) isoforms function as calcium sensor in post-Golgi transport although the precise transport step and compartment(s) concerned are still not fully resolved. As syt7 has been proposed to operate in lysosomal exocytosis and in exocytosis of large dense core vesicles (LDCVs), we have addressed the distribution of endogenous syt7 in insulin-secreting cells. These cells express different syt7 isoforms comparable to neurons. According to subcellular fractionation and quantitative confocal immunocytochemistry, syt7 is not found on LDCVs or on synaptic-like microvesicles but colocalizes with Rab7 on endosomes and to structures near to or at the plasma membrane. Similarly, endogenous syt7 was absent from LDCVs in pheochromocytoma PC12 cells. In contrast, syt7 localised to lysosomes in both, PC12 cells and hippocampal neurons. In conclusion, endogenous syt7 shows a wider distribution than previously reported but does not qualify as vesicular calcium sensor in SLMV or LDCV exocytosis according to its localisation. PMID- 17277933 TI - Cataleptic effects of gamma-hydroxybutyrate (GHB), its precursor gamma butyrolactone (GBL), and GABAB receptor agonists in mice: differential antagonism by the GABAB receptor antagonist CGP35348. AB - RATIONALE: Gamma-hydroxybutyrate (GHB) is used to treat narcolepsy but is also abused. GHB has many actions in common with the GABA(B) receptor agonist baclofen. OBJECTIVE: To further study the role of GABA(B) receptors in the effects of GHB. MATERIALS AND METHODS: The experiments examined the ability of the GABA(B) receptor antagonist CGP35348 to attenuate GHB-induced catalepsy in comparison with its ability to attenuate the cataleptic effects of GABA(B) receptor agonists. RESULTS: In C57BL/6J mice, GHB, the GHB precursor gamma butyrolactone (GBL), and the GABA(B) receptor agonists baclofen and SKF97541 all produced catalepsy but differed in potency (i.e., SKF97541>baclofen>GBL>GHB) and in onset of action. The cataleptic effects of drug combinations were assessed at the time of peak effect of each compound, i.e., 60 min after CGP35348 and 60, 30, 30, and 15 min after baclofen, SKF97541, GHB, and GBL, respectively. At 100 mg/kg, CGP35348 shifted the dose-response curves of baclofen and SKF97541 to the right but not those of GHB and GBL; at 320 mg/kg, CGP35348 shifted the curves of all four compounds to the right. CONCLUSIONS: The finding that CGP35348 was about threefold less potent to antagonize GHB and GBL than baclofen and SKF97541 is further evidence that the mechanisms mediating the effects of GHB and GABA(B) agonists are not identical. Differential involvement of GABA(B) receptor subtypes, or differential interactions with GABA(B) receptors, may possibly explain why GHB is effective for treating narcolepsy and is abused whereas baclofen is not. PMID- 17277934 TI - Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol. AB - RATIONALE: The stop-signal reaction time (SSRT) task measures inhibition of a response that has already been initiated, i.e. the ability to stop. 'Impulsive' human subjects, e.g. with attention deficit and hyperactivity disorder (ADHD), have longer SSRTs. Both SSRT and go-trial reaction time (GoRT) may be sensitive to drugs such as d-amphetamine, methylphenidate and modafinil, both in normal subjects and those with ADHD. OBJECTIVES: To investigate the effects of modafinil (3, 10, 30 and 100 mg/kg) and methylphenidate (0.3, 1.0 and 3.0 mg/kg) on SSRT task performance in the rat. To investigate the possible contribution of dopamine receptors in the action of these drugs using the mixed D1/D2 dopamine receptor antagonist cis-flupenthixol. RESULTS: Modafinil significantly decreased SSRT with little effect on GoRT but only in rats with slow baseline SSRTs. Fast SSRTs were not changed by modafinil. Methylphenidate decreased GoRTs of all rats. However, methylphenidate had baseline-dependent effects on SSRT, decreasing SSRT in slow responders but increasing SSRT in fast responders. Cis-flupenthixol (0.01, 0.04 and 0.125 mg/kg) had no effects on SSRT but increased GoRT at higher doses. At the lowest dose (0.01 mg/kg), cis-flupenthixol failed to disrupt the SSRT decreasing effects of either modafinil or methylphenidate, whereas at 0.04 mg/kg, the cis-flupenthixol-dependent increase in GoRT was antagonised by methylphenidate but not by modafinil. CONCLUSIONS: This evidence supports a hypothesis that stop and go processes are under control of distinct neurochemical mechanisms. PMID- 17277935 TI - Influence of nicotine on positive affect in anhedonic smokers. AB - RATIONALE: The possibility that individuals administer nicotine to self-regulate persistent negative affect has received interest as a possible explanation for the high prevalence of affectively vulnerable smokers. Relatively overlooked, however, is the possibility that smokers might also self-administer nicotine to elevate low positive affect. OBJECTIVES: This study examined whether nicotine administration augmented anhedonic smokers' positive affective response to a positive mood induction. MATERIALS AND METHODS: Fifty regular smokers (50% female) underwent two positive mood inductions during which they smoked either a nicotinized or denicotinized cigarette in counterbalanced order. Positive affect was assessed before and at two time points after smoking. RESULTS: Random effects regression showed a significant anhedonia by condition-by-time interaction [t(181)=-2.01, p = 0.04], supporting the hypothesis that anhedonia moderated nicotine's effect on changes in positive affect. Simple effect analyses showed a significant condition-by-time interaction among high anhedonic smokers [t(91)= 2.47, p = 0.01] but not among less anhedonic smokers [t(91)= 0.34, p = 0.73]. CONCLUSION: Smoking nicotine vs placebo heightened anhedonic smokers' ability to be induced into a positive mood, whereas nicotine had no effect on more hedonic smokers' positive mood. PMID- 17277937 TI - Reproducibility of onset and recovery oxygen uptake kinetics in moderately impaired patients with chronic heart failure. AB - Oxygen (O2) kinetics reflect the ability to adapt to or recover from exercise that is indicative of daily life. In patients with chronic heart failure (CHF), parameters of O2 kinetics have shown to be useful for clinical purposes like grading of functional impairment and assessment of prognosis. This study compared the goodness of fit and reproducibility of previously described methods to assess O2 kinetics in these patients. Nineteen CHF patients, New York Heart Association class II-III, performed two constant-load tests on a cycle ergometer at 50% of the maximum workload. Time constants of O2 onset- and recovery kinetics (tau) were calculated by mono-exponential modeling with four different sampling intervals (5 and 10 s, 5 and 8 breaths). The goodness of fit was expressed as the coefficient of determination (R2). Onset kinetics were also evaluated by the mean response time (MRT). Considering O2 onset kinetics, tau showed a significant inverse correlation with peak- VO2 (R = -0.88, using 10 s sampling intervals). The limits of agreement of both tau and MRT, however, were not clinically acceptable. O2 recovery kinetics yielded better reproducibility and goodness of fit. Using the most optimal sampling interval (5 breaths), a change of at least 13 s in tau is needed to exceed normal test-to-test variations. In conclusion, O2 recovery kinetics are more reproducible for clinical purposes than O2 onset kinetics in moderately impaired patients with CHF. It should be recognized that this observation cannot be assumed to be generalizable to more severely impaired CHF patients. PMID- 17277938 TI - Mechanomyographic assessment of contractile properties within seven segments of the human deltoid muscle. AB - The aim of this study was to determine, by a non-invasive whole muscle mechanomyographic technique (wMMG), how muscle segment contractile properties varied within the segments of the multifunctional deltoid muscle, and how such variations in contractile properties may reflect the muscle segment's function and fibre type composition. We hypothesised that muscle segment contractile properties, consistent with slower twitch muscle fibre populations, would be associated with the deltoid's prime mover abductor muscle segment (middle head), rather than the prime mover flexor and extensor muscle segments (anterior and posterior heads). Eighteen healthy and athletic University students (nine males and nine females; mean age 20-24 years) volunteered for this study. Each subject's right upper limb was secured with the forearm flexed to 30 degrees and the shoulder in 45 degrees of abduction. The wMMG laser sensor was positioned perpendicular to the middle of each muscle segment, to record the involuntary lateral displacement of the muscle belly following a maximal, single twitch, percutaneous neuromuscular stimulation (PNS) [180 V (max.); 80 mA (max.); 50 mus]. Ten trials were recorded from each of the seven deltoid segments for a total of 70 trials per subject. From each segment, eight variables were analysed from the recorded wMMG waveforms; maximal displacement (D (max)); delay time (T (d)); contraction time (T (c)); sustain time (T (s)); relaxation time (T (r)) and half relaxation time ((1/2)T (r)), average rate of contraction (ARC) and the average rate of relaxation (ARR). The results indicated that the contractile properties of the seven segments of the deltoid muscle showed significant (P < 0.05) variation in a medial to lateral direction. Medially the strap-like segments of the anterior (S1, S2) and posterior heads (S4-S7), with larger moment arms for shoulder flexion and extension respectively, had the fastest contractile properties. In contrast the multipennate segment 3, with the largest moment arm for shoulder abduction, had the slowest contractile properties (P < 0.05). Muscle segment contractile properties were matched to the biomechanical and architectural characteristics of the individual muscle segments. PMID- 17277936 TI - From anxiety to autism: spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats. AB - RATIONALE: Social behaviors are disrupted in several psychiatric disorders. The amygdala is a key brain region involved in social behaviors, and amygdala pathology has been implicated in disease states ranging from social anxiety disorder to autism. OBJECTIVE: To test the effects of progressive disruption of the inhibitory function within the basolateral nucleus of the amygdala (BLA) on conspecific social interaction in rats and investigate functional networks from the ventral medial prefrontal cortex (mPFCv) to the BLA. MATERIALS AND METHODS: BLA inhibitory tone was disrupted by priming it with the stress-peptide corticotrophin releasing factor (CRF) receptor agonist urocortin 1 (Ucn 1, 6 fmol), or by selective lesioning of a subset of BLA-GABAergic interneurons containing neurokinin 1 receptors using the targeted toxin SSP-Saporin. The effects of the disruption of GABAergic tone in the BLA were examined using a repeated exposure and habituation paradigm of social interaction (SI/h). Lesions and selectivity of lesions were confirmed postmortem. Additionally, effects of stimulating mPFCv on cFos activity in interneurons of the BLA were examined. RESULTS: Rats primed with Ucn 1 showed persistent social inhibition, which could be overcome with habituation, putatively modeling social anxiety. Rats with a selective lesioning of a subset of GABAergic interneurons in the BLA exhibited persistent social inhibition that was not reversed by SI/h paradigm. We also demonstrate selective functional inputs to this subset of interneurons when mPFCv was activated. CONCLUSIONS: These models with different gradations of disrupted BLA inhibition could help to study social dysfunction in disorders ranging from social anxiety to autism spectrum disorders. PMID- 17277940 TI - Avian-like attributes of a virtual brain model of the oviraptorid theropod Conchoraptor gracilis. AB - An almost complete adult endoneurocranium of Conchoraptor gracilis Barsbold 1986 (Oviraptoridae; ZPAL MgD-I/95), discovered at the Hermiin Tsav locality (the Upper Cretaceous) in Mongolia, is analyzed. A virtual model of the endoneurocranial cavity was derived from CT scans and represents the most complete maniraptoran endocast to date. It displays reduced olfactory bulbs, large cerebral hemispheres in contact with the expanded cerebellum, an epiphysial projection, optic lobes displaced latero-ventrally, presumptive cerebellar folia, enlarged cerebellar auricles, and a deep medulla oblongata with a prominent ventral flexure. Contrary to Archaeopteryx, the shortened olfactory tract and cerebellum overtopping cerebral hemispheres of Conchoraptor resemble conditions in modern birds. Calculating brain mass relative to body mass indicates that Conchoraptor falls within the range of extant birds, whereas Archaeopteryx occupies a marginal position. Most of the endoneurocranial attributes, however, have a less birdlike appearance in Conchoraptor than do corresponding structures in Archaeopteryx and modern birds in which 1) postero-laterally expanded hemispheral domains broadly overlap the optic lobes, 2) the epiphysis projects to the posterior cerebrum, 3) lateral extension of the optic lobes substantially decreases a brain length-to-width ratio, 4) optic lobe and anterior hindbrain are superposed in lateral view, and 5) cerebellar and midbrain compartments are in distinct superposition. The endoneurocranial characteristics of Conchoraptor, taken together, suggest that the animal had a keen sense of vision, balance, and coordination. The data presented in this study do not allow an unambiguous assessment whether the avian-like endoneurocranial characteristics of the flightless Conchoraptor evolved convergently to those of avian theropods, or indicate a derivation of oviraptorosaurs from volant ancestors. PMID- 17277939 TI - Assessment of post-competition peak blood lactate in male and female master swimmers aged 40-79 years and its relationship with swimming performance. AB - The main purpose of this study was to measure the post-competition blood lactate concentration ([La](b)) in master swimmers of both sexes aged between 40 and 79 years in order to relate it to age and swimming performance. One hundred and eight swimmers participating in the World Master Championships were assessed for [La](b) and the average rate of lactate accumulation (La'; mmol l(-1) s(-1)) was calculated. In addition, 77 of them were also tested for anthropometric measures. When the subjects were divided into 10-year age groups, males exhibited higher [La](b) than women (factorial ANOVA, P < 0.01) and a steeper decline with ageing than female subjects. Overall, mean values (SD) of [La](b) were 10.8 (2.8), 10.3 (2.0), 10.3 (1.9), 8.9 (3.2) mmol l(-1) in women, and 14.2 (2.5), 12.4 (2.5), 11.0 (1.6), 8.2 (2.0) mmol l(-1) in men for, respectively, 40-49, 50-59, 60-69, 70-79 years' age groups. When, however, [La](b) values were normalised for a "speed index", which takes into account swimming speed as a percentage of world record, these sex-related differences, although still present, were considerably attenuated. Furthermore, the differences in La' between males and females were larger in the 40-49 age group (0.34 vs 0.20 mmol l(-1) s(-1) for 50-m distance) than in the 70-79 age group (0.12 vs 0.14 mmol l(-1) s(-1) for 50-m distance). Different physiological factors, supported by the considered anthropometric measurements, are suggested to explain the results. PMID- 17277941 TI - Afforestation of abandoned farmland with conifer seedlings inoculated with three ectomycorrhizal fungi - impact on plant performance and ectomycorrhizal community. AB - The aim of a 3-year study was to investigate whether inoculation of Pinus sylvestris L. and Picea abies (L.) Karst. seedlings with mycorrhizas of Cenococcum geophilum Fr., Piceirhiza bicolorata, and Hebeloma crustuliniforme (Bull.) Quel. has any impact on: 1) survival and growth of outplanted seedlings on abandoned agricultural land, and 2) subsequent mycorrhizal community development. For inoculation, the root system of each plant was wrapped in a filter paper containing mycelium, overlaid with damp peat-sand mixture and wrapped in a paper towel. In total, 8,000 pine and 8,000 spruce seedlings were planted on 4-ha of poor sandy soil in randomized blocks. Already after the first year natural mycorrhizal infections prevailed in the inoculated root systems, and introduced mycorrhizas were seldom found. Yet, the seedlings that had been pre inoculated with C. geophilum and the P. bicolorata during the whole 3-year period showed significantly higher survival and growth as compared to controls. Moreover, the independent colonization of roots by C. geophilum and the P. bicolorata from natural sources was also observed. A diverse mycorrhizal community was detected over two growing seasons in all treatments, showing low impact of inoculation on subsequent fungal community development. A total of 19 additional ectomycorrhizal morphotypes was observed, which clustered into two well-separated groups, according to host tree species (pine and spruce). In conclusion, the results showed limited ability to increase tree survival and growth, and to manipulate the mycorrhizal community even by extensive pre inoculations, indicating that fungal community formation in root systems is governed mainly by environmental factors. PMID- 17277942 TI - GintMT1 encodes a functional metallothionein in Glomus intraradices that responds to oxidative stress. AB - A full-length metallothionein (MT) gene (GintMT1) was isolated from Glomus intraradices extraradical mycelium. This is the first MT gene reported in the genus Glomus, third in the Glomeromycota. Functional analysis of GintMT1 in a MT defective Saccharomyces cerevisiae strain indicates that it encodes a functional MT. Gene expression analyses revealed that the transcript levels of GintMT1 were elevated in mycelia treated with 5 mM Cu or paraquat but inhibited in mycelia treated with 50 microM Cu or 450 microM Cd. The elevated expression of GintMT1 in the 5 mM Cu-treated mycelia together with the ability of GintMT1 to provide tolerance to a Cu-sensitive yeast suggests that GintMT1 might afford protection against Cu. Induction of GintMT1 expression by paraquat and 5 mM Cu, treatments that also produced an oxidative damage to the fungal membranes, suggests that GintMT1 may play a role in the regulation of the redox status of the extraradical mycelium of G. intraradices. PMID- 17277943 TI - Arbuscular mycorrhizal structure and fungi associated with mosses. AB - We investigated the colonization and diversity of arbuscular mycorrhizal (AM) fungi associated with 24 moss species belonging to 16 families in China. AM fungal structures, i.e. spores, vesicles, hyphal coils (including intracellular hyphae), or intercellular nonseptate hyphae, were found in 21 moss species. AM fungal structures (vesicles, hyphal coils, and intercellular nonseptate hyphae) were present in tissues of 14 moss species, and spores and nonseptate hyphae on the surface of gametophytes occurred in 15 species. AM fungal structures were present in 11 of the 12 saxicolous moss species and in six of the ten terricolous moss species, but absent in two epixylous moss species. AM fungal structures were only observed in moss stem and leaf tissues, but not in rhizoids. A total of 15 AM fungal taxa were isolated based on trap culture with clover, using 13 moss species as inocula. Of these AM fungi, 11 belonged to Glomus, two to Acaulospora, one to Gigaspora, and one to Paraglomus. Our results suggest that AM fungal structures commonly occur in most mosses and that diverse AM fungi, particularly Glomus species, are associated with mosses. PMID- 17277944 TI - Unique pattern of R-gene variation within populations in Arabidopsis. AB - An understanding of the variation pattern in disease resistance (R) genes is essential for its use in breeding programs aimed at neutralizing the threat of pathogens. Although the variation between populations is well known, there is little research about R-gene variation patterns within populations. Here, we investigate the polymorphism at three R-gene loci of 39 individual plants from nine populations of Arabidopsis thaliana. Our data suggest that alleles of each locus from individuals within a local population were either nearly identical, or highly diverse as ones between populations. The vast majority (92.5%) of within population variation was shared globally, with high levels of allelic diversity (up to 11.7%) and abundant diverse-alleles. This unique pattern of within population variation at R-loci suggests that individual plants within a population had the great potential to maintain a high level of globally-shared polymorphisms, and that the diversifying selection was the major force maintaining such polymorphisms. Consequently, the shared-polymorphism became recyclable for new R-genes, as the corresponding avirulence re-emerges in pathogen populations. PMID- 17277945 TI - Prime-trial processing demands and their impact on distractor processing in a spatial negative priming task. AB - A spatial negative priming (NP) paradigm was used where trials were presented in pairs, first the 'prime' and then the 'probe', and where participants responded manually to a target's location. In Experiment 1, three prime-trial types were used: distractor-plus-target, predictable distractor-only, and unpredictable distractor-only, with prime-probe trial onset delays of 2, 5 or 10 s (NP longevity). In Experiment 2, the latter two prime-trials were employed with onset delays of 75 and 750 ms (distractor response activation-inhibition sequence). With the exception of the 10 s onset delay, the spatial NP effect data (NP size, longevity, distractor response activation-inhibition sequence) was the same for all three prime-trial types. Thus, the varying processing demands associated with each of the prime-trial types (e.g., selection, intervening response) did not alter prime distractor processing so that they differentially contributed to the spatial NP process. The three prime-trial types can be used interchangeably, within limits, to study the NP process. PMID- 17277946 TI - Micronucleus frequency in peripheral blood lymphocytes and buccal mucosa cells of copper smelter workers, with special regard to arsenic exposure. AB - Occupational exposure in copper smelters may produce various adverse health effects including cancer which, according to available epidemiologic data, is associated mainly with exposure to arsenic. Despite a number of well-documented studies reporting an increased risk of cancer among copper smelters workers, the data on genotoxic effects in this industry are scarce. In view of the above, an assessment of micronuclei (MN) frequency in peripheral blood lymphocytes and buccal epithelial cells from copper smelter workers was undertaken. Additionally, the clastogenic/aneugenic effect in lymphocytes was assessed with the fluorescence in situ hybridization (FISH). The study was conducted in three copper smelters in southwestern Poland. The subjects (n = 72) were enrolled among male workers at departments where As concentration in the air was up to at 80 microg/m(3). Exposure was assessed by measurement of arsenic concentration in urine and toenail samples. The control group (n = 83) was recruited from healthy male individuals living in central Poland who did not report any exposure to known genotoxins. The results of our study showed a significant increase in MN frequency in peripheral blood lymphocytes and in buccal epithelial cells of smelter workers, compared to the controls (7.96 +/- 4.28 vs. 3.47 +/- 1.70 and 0.98 +/- 0.76 vs. 0.50 +/- 0.52, respectively). The FISH technique revealed the presence of clastogenic and aneugenic effects in peripheral blood lymphocytes in both groups. The clastogenic effect was slightly more pronounced in the smelter workers; however, the difference was not statistically significant. The mean arsenic concentrations in urine (total arsenic species) and in toenail samples in the exposed group were 54.04 +/- 42.26 microg/l and 7.63 +/- 7.24 microg/g, respectively, being significantly different from control group 11.01 +/- 10.84 microg/l and 0.51 +/- 0.05 microg/g. No correlation between As content in urine or toenail samples and the genotoxic effect was found under study. PMID- 17277947 TI - Percutaneous vertebroplasty in tumoral osteolysis. AB - Percutaneous vertebroplasty is a minimally invasive, radiologically guided procedure in which bone cement is injected into structurally weakened or destructed vertebrae in order to achieve additional biomechanical stability. In addition to treating osteoporotic vertebral fractures, this technique gains popularity to relieve pain by stabilizing vertebrae compromised by, for example, metastases, aggressive hemangiomas or multiple myeloma that are at risk of pathologic fracture. Since conservative treatment with narcotic analgesics, bed rest, biphosphonates and back bracing for several weeks is often ineffective and the analgesic effect of radiation therapy is delayed, percutaneous vertebroplasty may play a beneficial role in the management of metastases to the spine. PMID- 17277948 TI - A simple method to estimate cardiac function during routine multi-row detector CT exams. AB - Cardiac dysfunction may be suggested at computed tomography (CT) exams by the presence of morphological abnormalities such as cardiac enlargement and thickening of the pulmonary interlobular septa. However, these morphological signs are non specific. We evaluated whether right-to-left cardiac transit time of contrast during single-level timing scans could predict the cardiac output and ejection fraction. In a consecutive group of 100 patients referred for body CT, a preliminary single-level study was used to measure the right-to-left ventricular transit time of intravenously injected contrast medium. In all these patients, the cardiac index (cardiac output corrected for body surface area, CI) and ejection fraction (EF) were calculated using cardiac magnetic resonance imaging (CMR). Data of the first half (50 patients, group A) were used to establish a method and concept to predict the cardiac index and ejection fraction with CT. The method was validated in the next half (50 patients, group B) by comparing the predicted CT results with those obtained with CMR. There was a good correlation of the observed CI with CMR and observed transit time on CT in group B (P < 0.05; R(2) 0.70 ). Functional CT estimates of CI and EF in group B correlated well with the CMR results for CI and EF (P < 0.05; R(2) 0.66 for CI and P < 0.05; R(2) 0.49 for EF). The presence of a right-to-left ventricular transit time of more than 10.5 s indicated cardiac dysfunction with a specificity and positive predictive value of 100%. Right-to-left transit time obtained during routine body CT exams can provide valuable physiological information on global cardiac function. PMID- 17277949 TI - Regulation of the chitobiose-phosphotransferase system in Vibrio cholerae. AB - Vibrio cholerae harbours a phosphotransferase system (PTS) enabling the organism to utilise chitosan oligosaccharide, e.g. derived from deacetylated chitin. As shown recently, this utilization system is encoded by the ORFs VC1281-1283 (Meibom et al. in Proc Natl Acad Sci USA, 101:2524-2529, 2004). By using a transcriptional reporter fusion technique, we identified the regulator of the system and characterised gene expression. Furthermore, we found that gene expression of this PTS system is influenced by catabolite regulation and also by an Mlc homologue (VC2007), which in E. coli is a global regulator of sugar metabolism. PMID- 17277950 TI - Similar topographical distribution of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonism-dementia complex in people living in the Kii peninsula of Japan suggests a single tauopathy. AB - The presence of many neurofibrillary tangles (NFTs) in the central nervous system is a hallmark of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) in people living in the Kii peninsula of Japan and in the island of Guam. To determine whether or not ALS and PDC are on a spectrum of a single tauopathy, we investigated the topography of NFTs semiquantitatively in two patients with ALS, three with PDC, and two with "PDC plus ALS" (PDC followed by ALS) on the basis of clinical symptoms. NFTs were counted under x100 magnification of Gallyas-Braak stained preparations and were plotted on brain maps of the hemisphere, brainstem, and the spinal cord. In all cases, the hippocampus, particularly in the CA1 field, the parahippocampal gyrus, amygdaloid nucleus, and the temporal poles were most severely affected. In the neocortex, layers II-III were more severely affected by NFTs than layers V-VI. In the spinal cord, a few NFTs were revealed in the intermediate gray. NFTs were dense in all cases of PDC and "PDC plus ALS" and variable in density in ALS cases, although the topography was similar between them. We conclude that similar topographical distribution of NFTs in ALS and PDC in people living in the Kii peninsula of Japan suggests a single tauopathy. PMID- 17277951 TI - Phenylacetate and benzoate clearance in a hyperammonemic infant on sequential hemodialysis and hemofiltration. AB - An infant with a suspected inborn metabolism error was treated with a metabolic cocktail of intravenous sodium phenylacetate (NaPh) and sodium benzoate (NaBz) for hyperammonemia. Sequential hemodialysis (HD) then hemofiltration (HF) was performed due to hyperammonemia. Dialytic and convective clearance (K; ml/min) of ammonia, NaPh, and NaBz was measured. The K of ammonia was 57 and 37 for HD and HF, respectively. The K of NaBz was 37 and 12 for HD and HF, respectively. The K of NaPh was 38 and 14 ml/min for HD and HF, respectively. Despite high clearance of both NaPh and NaBz by HD and HF, the hyperammonemia was corrected. PMID- 17277952 TI - Long-term efficacy of low-density lipoprotein apheresis for focal and segmental glomerulosclerosis. AB - Recently, there have been reports on the efficacy of low-density lipoprotein (LDL) apheresis (LDL-A) for focal and segmental glomerulosclerosis (FSGS) in pediatric patients. However, there have been few reports on the long-term efficacy of LDL-A for FSGS in such patients. We report here a case of long-term efficacy of LDL-A for FSGS. The patient was a 13-year-old boy with FSGS who presented with steroid-resistant and cyclosporine-resistant nephrotic syndrome and hyperlipidemia. LDL-A was performed 24 times on one year. Following LDL-A, serum concentrations of LDL, very low-density lipoprotein (VLDL), apoprotein B, and vascular endothelial growth factor significantly decreased, and urinary excretion of protein also decreased. In addition, 3 years after LDL-A, the pathology findings on a second renal biopsy had improved. The patient has been in remission from FSGS for 12 years since LDL-A. These findings suggest that LDL-A may be useful in maintaining long-term remission from pediatric FSGS. PMID- 17277953 TI - Vesicoureteral reflux: surgical and endoscopic treatment. AB - The optimal management of vesicoureteral reflux (VUR) is quite controversial. For many years, only antibiotic prophylaxis and open surgery were considered possible options. Since the first descriptions in the early 1980s, endoscopic treatment (ET) has gained popularity and is now considered a valid alternative both to open surgery and antibiotic prophylaxis. Many surgical antireflux techniques have been described in the past 50 years. The general principle of reflux surgery, usually defined as ureteric reimplantation, is elongation of the submucosal ureteral tunnel with creation of a flap-valve mechanism. The antireflux operation can also be carried out laparoscopically, either extravesically or intravesically (pneumovesicum). Open surgery is associated with a high success rate (>95%) regardless of the technique adopted. However, because it is invasive, it is limited to selected cases. Laparoscopic technique is less invasive, but the mean operative time is much longer and results depend significantly on the learning curve. ET involves injecting material endoscopically into the submucosal space under the ureteric orifice. It is associated with a good success rate (about 80% after one injection). Advantages of this minimally invasive treatment include repeatability and the fact that postoperative complications are rare. With a second injection, after few months if needed, the success rate of ET approaches that of open surgery. Our 20-year experience in ET is described in detail in this paper, as this technique has changed the management algorithm for VUR dramatically. PMID- 17277954 TI - Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis. AB - We prospectively evaluated the effects of L-carnitine supplementation on plasma free carnitine (FC) levels, serum lipid profile, and erythropoietin (rhEPO) requirement in 24 children treated with peritoneal dialysis (PD; n=16) or hemodialysis (HD; n=8). The study was divided into a 3-month observation period, and a 3-month treatment period during which patients received 20 mg/kg per day of L-carnitine given orally. Clinical, biochemical, and hematological data were collected every 3 months. FC levels were measured in plasma and peritoneal dialysate by tandem mass spectrometry. There were no statistically significant changes in lipid levels, hemoglobin, or rhEPO requirements during the course of the study. Fifteen patients (13 PD, 2 HD) had plasma FC levels measured before and after treatment; FC levels increased from 32.1 +/- 14.1 micromol/l to 80.9 +/ 38.7 micromol/l (P<0.001). In PD patients, dialysate FC losses increased from 106 +/- 78 micromol/day at baseline to 178 +/- 119 micromol/day after supplementation. Positive correlations between FC plasma levels and dialysate levels (R=0.507) or daily excretion (R=0.603) were found after treatment. In our case series, an oral dose of 20 mg/kg per day of L-carnitine restored FC levels and produced a positive carnitine balance with no significant effects on hematological parameters or lipid profile over a 3-month period. Prolonged treatment duration may be required to obtain significant results. PMID- 17277955 TI - [Cardiotoxic and neurotoxic effects after accidental intravascular bupivacaine administration. Therapy with lidocaine propofol and lipid emulsion]. AB - Accidental intravascular administration of bupivacaine can cause severe neurotoxic and cardiotoxic effects. We report a case of suspected bupivacaine intoxication due to intravascular injection via an epidural catheter and treatment with lidocaine, propofol, and a 20% lipid emulsion resulting in fast resolution of cardiotoxic and neurotoxic effects. Possible mechanisms of action of the medications used are discussed. PMID- 17277956 TI - [Laryngopharyngeal morbidity following general anaesthesia. Anaesthesiological and laryngological aspects]. AB - Laryngeal and pharyngeal complaints are among the subjective problems most frequently reported by patients after general anaesthesia involving endotracheal intubation, others being pain, nausea and vomiting. Hoarseness, sore throat, and vocal cord injuries restrict patients' social lives, and in some cases also their working lives. The most frequent types of laryngeal injury are swollen mucosa and haematoma of the vocal cords. Vocal cord paralysis occurs much less frequently. Knowledge of the pathophysiological aspects and other relevant factors associated with laryngopharyngeal morbidity are essential cornerstones of quality assurance in perioperative respiratory tract management. In this review specific sections are devoted to the implications of anaesthesia involving endotracheal intubation and laryngeal masks for laryngopharyngeal morbidity, and also particular aspects of thyroid gland surgery, cardiothoracic and bariatric surgery and obstetric and paediatric anaesthesia, and medicolegal aspects. PMID- 17277957 TI - [Realisation of material costs in anaesthesia. Alternatives to the reimbursement via diagnosis-related groups]. AB - BACKGROUND AND GOAL: For reimbursement via diagnosis-related groups (DRG), lump compensation-based payment of medical cases in German hospitals requires a case related measuring and billing of resources that has to be consistent with DRG guidelines. Only through this, can the real costs be compared with the standard costs as calculated by the hospital reimbursment system (InEK) on a case-related basis and the DRG-specific break-even level be identified. METHODS: In the present paper the authors introduce and validate two newly created alternative methods for case-related allocation of material costs in the field of anaesthesia. Method 1 allows online documentation of material costs via pre defined anaesthesia standards. This full cost method is suitable for hospitals that have implemented an electronic hospital information system in their daily clinical documentation routine. For other hospitals method 2 could be applicable as the case-related allocation of material costs is done retrospectively based on the data collected in an electronic anaesthesia protocol record system (andoc, medlinq). RESULTS: Method 1 makes it possible to allocate 90.3% of anaesthesia related material costs to a specific case corresponding to a Pearsson coefficient of 0.77. After iterative improvement through optimisation of modules the documentation quality could be raised to >98% and a Pearsson coefficient of 0.96. Although the expense for implementation and maintenance is considerable, the necessary documentation work for the clinician is low. Method 2 demands no further clinical effort in documentation and implementation and 49.1% of all material costs can be assigned on a case-related basis. CONCLUSIONS: The online documentation of material costs via predefined anaesthesia standards accounts for nearly all material costs in anaesthesia and only a negligible documentation effort is necessary for the clinician. Nevertheless, a complex and time-consuming configuration of standards and a continuous iterative alignment of the modules with the actual processes are required. Due to its process-orientated character, method 1 can also be used for workflow optimisation in terms of standard operating procedures (SOPs). Allocation of material costs with data from the electronic anaesthesia record system is a method that can be easily implemented but only a partial case relation is rendered possible. PMID- 17277958 TI - Cryogenic grinding pre-treatment improves extraction efficiency of fluoroquinolones for HPLC-MS/MS determination in animal tissue. AB - An efficiency extraction of fluoroquinolones in chicken muscle was achieved by pulverizing it in a freezer mill before treatment with NaOH (10mM)/MeCN (1:1). The improvement of cryogenic grinding in the extraction was demonstrated for the same piece (whole leg) of four chickens treated with enrofloxacin in equal doses. A confirmatory method based on high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was used to analyze the extracts. The chromatographic separation was achieved in 5 min with a Synergi Fusion-RP 80A (50 x 2 mm, 4 microm) column filled with a hybrid polymer. The HPLC was coupled with a detector based in a quadrupole-linear ion trap Q-TRAP that allows a confirmatory detection according to the European legislation. The specificity of the method was assessed by testing a number of representative blank muscle samples (n = 10) to verify the absence of potential interfering compounds. The limits of detection and quantitation were 2 and 5 ng g(-1) of quinolones in muscle samples, respectively. The chromatographic method was demonstrated to be linear for the range studied (5 500 ng g(-1)) with the P value for lack-of-fit in the ANOVA table greater or equal to 0.10 (calibration coefficient 0.9998 and 0.9996 for ciprofloxacin and enrofloxacin, respectively). The mean intra-day relative standard deviation (RSD) (n = 6, c = 50 ng g(-1)) was 6%; inter-day assay gave a RSD of 12%. The extraction and clean-up were carried out in one step with very satisfactory recovery data (between 65 and 101%). PMID- 17277960 TI - [Bisphosphonates in the therapy of fibrous dysplasia. Relevant data and practical aspects]. AB - Fibrous dysplasia covers a variety of rather different clinical pictures. Its therapy therefore has to be individually adapted. In addition to the orthopaedic surgeon, endocrinologists and craniofacial surgeons are also involved in the process. In the present contribution the role of modern bisphosphonates as a conservative treatment strategy is discussed with regard to the prevalent therapeutic possibilities. The literature as well as personal experience show them to be an especially valid option for the treatment of polyostotic fibrous dysplasia and the various syndromes. PMID- 17277959 TI - The relevance of the IgG subclass of autoantibodies for blister induction in autoimmune bullous skin diseases. AB - Autoimmune bullous skin diseases are characterized by autoantibodies and T cells specific to structural proteins maintaining cell-cell and cell-matrix adhesion in the skin. Existing clinical and experimental evidence generally supports a pathogenic role of autoantibodies for blister formation. These autoantibodies belong to several IgG subclasses, which associate with different functional properties and may thus determine the pathogenic potential of IgG antibodies. In pemphigus diseases, binding of IgG to keratinocytes is sufficient to cause intraepidermal blisters without engaging innate immune effectors and IgG4 autoantibodies seem to mainly mediate acantholysis. In contrast, in most subepidermal autoimmune blistering diseases, complement activation and recruitment and activation of leukocytes by autoantibodies are required for blister induction. In these conditions, tissue damage is thought to be mainly mediated by IgG1, but not IgG4 autoantibodies. This review summarizes the current knowledge on the pathogenic relevance of the IgG subclass of autoantibodies for blister formation. Characterization of the pathogenically relevant subclass(es) of autoantibodies not only provides mechanistic insights, but should greatly facilitate the development of improved therapeutic modalities of autoimmune blistering diseases. PMID- 17277961 TI - [Introduction to bisphosphonates. History and functional mechanisms]. AB - The development of bisphosphonates is based on our studies in the 1960s on the mechanism of mineralization. It was shown that biological fluids contained mineralization inhibitors which we identified as inorganic pyrophosphate. Pyrophosphate, which, along with longer polyphosphates, has long been known as a water softener due to its inhibition of calcium carbonate formation, also has the ability to inhibit calcium phosphate crystal formation as well as dissolution. When given parenterally (but not orally), they also inhibit experimentally induced mineralization in vivo in animals. Their lack of effectiveness on oral application, as well as for bone destruction, is due to enzymatic cleavage in the body. We therefore sought analogues which had similar properties but were not biologically degraded. The bisphosphonates, which have a P-C-P instead of a P-O-P bond, fulfilled these criteria. They have been known since the middle of the 19th century and have also been used industrially as water softeners. We discovered that they bind to calcium phosphate crystals in the same way as pyrophosphate and inhibit calcium phosphate binding as well as its dissolution. In vivo, they inhibit mineralization as well as bone destruction. While the first process can be explained by a physicochemical mechanism, the second is cellular and involves the inhibition of the formation, lifespan and activity of osteoclasts. The molecular mechanism is dependent on the structure of the bisphosphonate. The structurally more simple molecules without nitrogen incorporate the P-C-P bond in ATP containing molecules and become toxic to the osteoclasts. The more active nitrogen containing bisphosphonates inhibit mevalonate metabolism due to the specific inhibition of farnesyl pyrophosphate synthase. This leads to a reduction in geranylgeranyl pyrophosphate, which is necessary for osteoclast survival. PMID- 17277962 TI - Outdoor cultivation of microalgae for carotenoid production: current state and perspectives. AB - Microalgae are a major natural source for a vast array of valuable compounds, including a diversity of pigments, for which these photosynthetic microorganisms represent an almost exclusive biological resource. Yellow, orange, and red carotenoids have an industrial use in food products and cosmetics as vitamin supplements and health food products and as feed additives for poultry, livestock, fish, and crustaceans. The growing worldwide market value of carotenoids is projected to reach over US$1,000 million by the end of the decade. The nutraceutical boom has also integrated carotenoids mainly on the claim of their proven antioxidant properties. Recently established benefits in human health open new uses for some carotenoids, especially lutein, an effective agent for the prevention and treatment of a variety of degenerative diseases. Consumers' demand for natural products favors development of pigments from biological sources, thus increasing opportunities for microalgae. The biotechnology of microalgae has gained considerable progress and relevance in recent decades, with carotenoid production representing one of its most successful domains. In this paper, we review the most relevant features of microalgal biotechnology related to the production of different carotenoids outdoors, with a main focus on beta-carotene from Dunaliella, astaxanthin from Haematococcus, and lutein from chlorophycean strains. We compare the current state of the corresponding production technologies, based on either open-pond systems or closed photobioreactors. The potential of scientific and technological advances for improvements in yield and reduction in production costs for carotenoids from microalgae is also discussed. PMID- 17277963 TI - Flow-FISH analysis and isolation of clostridial strains in an anaerobic semi solid bio-hydrogen producing system by hydrogenase gene target. AB - By using hydrogenase gene-targeted polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR), the predominant clostridial hydrogenase that may have contributed to biohydrogen production in an anaerobic semi-solid fermentation system has been monitored. The results revealed that a Clostridium pasteurianum like hydrogenase gene sequence can be detected by both PCR and RT-PCR and suggested that the bacterial strain possessing this specific hydrogenase gene was dominant in hydrogenase activity and population. Whereas another Clostridium saccharobutylicum-like hydrogenase gene can be detected only by RT-PCR and suggest that the bacterial strain possessing this specific hydrogenase gene may be less dominant in population. In this study, hydrogenase gene-targeted fluorescence in situ hybridization (FISH) and flow cytometry analysis confirmed that only 6.6% of the total eubacterial cells in a hydrogen-producing culture were detected to express the C. saccharobutylicum-like hydrogenase, whereas the eubacteria that expressed the C. pasteurianum-like hydrogenase was 25.6%. A clostridial strain M1 possessing the identical nucleotide sequences of the C. saccharobutylicum-like hydrogenase gene was then isolated and identified as Clostridium butyricum based on 16S rRNA sequence. Comparing to the original inoculum with mixed microflora, either using C. butyricum M1 as the only inoculum or co-culturing with a Bacillus thermoamylovorans isolate will guarantee an effective and even better production of hydrogen from brewery yeast waste. PMID- 17277964 TI - [Somatic complaints in mothers of children with developmental language disorders]. AB - BACKGROUND: In preliminary studies of mothers of children with developmental language disorders it was found that the mothers' quality of life was diminished and that they suffered from increased emotional disorders. Studies have shown that women with emotional problems also experience increased somatic afflictions. This phenomenon has not yet been confirmed in the context of mothers of children with developmental language disorders. MATERIALS AND METHODS: Ninety mothers (aged 21-48 years) of 90 preschoolers diagnosed with a developmental language disorder, but otherwise of normal development, were questioned using the Giessen Complaint Questionnaire (Giessener Beschwerdebogen, GBB), to assess their level of somatic complaints. The multivariate statistical method used was the regression analysis. RESULTS: In comparison to women of the same age in the normal population, the mothers in this study had significantly more somatic symptoms. This was shown to be true even for those mothers who, though specifically asked, could not name any particular illness. In mothers of children being treated for developmental language disorders, psychosomatic complaints occurred more frequently. The same result can be observed in mothers who perceived a lack of adequate support in caring for their children as opposed to those who perceived support to be adequate. CONCLUSIONS: Physicians and health workers treating children with developmental language disorders must reckon with a considerable number of mothers with somatic complaints. As these complaints often occur without any specific illness, they must be considered psychosomatic in nature. These findings are in accordance with earlier studies looking at the relationship between specific emotional disorders and diminished quality of life of those affected. Specific channels of help include utilization of self-help groups or mothers' groups, educational enhancement programs and speech therapists. PMID- 17277965 TI - [Extraesophageal reflux in patients suffering from Zenker's diverticulum]. AB - INTRODUCTION: Patients with Zenker's diverticulum often present with a hiatal hernia. Theoretically, the gastric acid fluid could rise up to the hypopharynx producing an injury to the mucosa of Killian's triangle and hypertrophy of the cricopharyngeal muscle. We performed dual-channel pH monitoring in healthy people as a control group and in patients with a Zenker's diverticulum to elucidate the relationship between Zenker's diverticulum and gastroesophageal reflux disease (GERD) as well as extraesophageal reflux (EER). METHODS: Patients with Zenker's diverticulum underwent dual-channel 24-h pH monitoring to exclude the possibility of an EER or a GERD. The measurements were performed in 4 patients preoperatively and postoperatively as well as in 14 patients only postoperatively. The control group consisted of healthy volunteers who did not suffer from a reflux disease (n=20). In each group we determined the number of refluxes, the fraction time, the RAI (reflux area index), and the DeMeester Score Index. In addition we classified the severity of the EER with a grading system which was developed in an earlier study in our department. RESULTS: Patients with a Zenker's diverticulum suffered significantly from EER (p<0.01). The difference between the patients measured preoperatively and the patients postoperatively was minor. More than 72% of the patients suffered from a severe EER. CONCLUSIONS: Patients with a Zenker's diverticulum have a high possibility of suffering from EER and GERD. The pathophysiology of this relationship can only be speculated. In addition to a cricopharyngeal myotomy, long-term therapy with a PPI (proton pump inhibitor) seems indicated. PMID- 17277966 TI - [Oesophageal tumours--what does the surgeon need from the radiologist?]. AB - Surgery is the most important therapeutic discipline for oesophageal cancers and the surgeon has specific questions for the radiologist which can require various imaging procedures. The radiological presentation is, for example, necessary for the topographic imaging of larger space occupying processes, the localization and axial spread of which are important for the surgical procedure chosen. Imaging diagnostics helps with the identification of R0 resectable patients. High resolution computed tomography (CT) of the mediastinum is used to clarify the spatial relationship between oesophageal cancer and the tracheobronchial system. This method also helps demonstrate the presence of fistulas in the tracheobronchial system or mediastinum. Using a neck or thorax CT, or a PET-CT distant metastases can be documented and a second tumour excluded. Imaging procedures gain additional significance for the evaluation of the T stage of the oesophageal tumour or the response to neoadjuvant therapy concepts, for which an earliest possible response evaluation is of great importance. Imaging procedures are also of importance in aftercare as it is sometimes possible and valuable to carry out surgery for local relapses. PMID- 17277968 TI - Risk of second non-hematological malignancies among 376,825 breast cancer survivors. AB - Breast cancer survivors are at increased risk of treatment-related second cancers. This study is the first to examine risk 30 or more years after diagnosis and to present absolute risks of second cancer which accounts for competing mortality. We identified 23,158 second non-hematological malignancies excluding breast in a population-based cohort of 376,825 one-year survivors of breast cancer diagnosed from 1943 to 2002 and reported to four Scandinavian cancer registries. We calculated standardized incidence ratios (SIR) and utilized a competing-risk model to calculate absolute risk of developing second cancers. The overall SIR for second cancers was 1.15 (95% confidence interval [CI] = 1.14 1.17). The SIR for potentially radiotherapy-associated cancers 30 or more years after breast cancer diagnosis was 2.19 (95% CI = 1.87-2.55). However, the largest SIRs were observed for women aged <40 years followed for 1-9 years. At 20 years after breast cancer diagnosis, the absolute risk of developing a second cancer ranged from 0.6 to 10.3%, depending on stage and age; the difference in the absolute risk compared to the background population was greatest for women aged <40 years with localized disease, 2.3%. At 30 years post breast cancer diagnosis, this difference reached 3.2%. These risks were small compared to the corresponding risk of dying from breast cancer. Although the absolute risks were small, we found persistent risks of second non-hematological malignancies excluding breast 30 or more years after breast cancer diagnosis, particularly for women diagnosed at young ages with localized disease. PMID- 17277969 TI - Osteoprogenitor response to low-adhesion nanotopographies originally fabricated by electron beam lithography. AB - It is considered that cells can use filopodia, or microspikes, to locate sites suitable for adhesion. This has been investigated using a number of mature cell types, but, to our knowledge, not progenitor cells. Chemical and topographical cues on the underlying substrate are a useful tool for producing defined features for cells to respond to. In this study, arrays of nanopits with different symmetries (square or hexagonal arrays with 120 nm diameters, 300 nm center centre spacings) and osteoprogenitor cells were considered. The pits were fabricated by ultra-high precision electron-beam lithography and then reproduced in polycarbonate by injection moulding with a nickel stamp. Using scanning electron and fluorescence microscopies, the initial interactions of the cells via filopodia have been observed, as have subsequent adhesion and cytoskeletal formation. The results showed increased filopodia interaction with the surrounding nanoarchitecture leading to a decrease in cell spreading, focal adhesion formation and cytoskeletal organisation. PMID- 17277970 TI - Stereological analysis of the poly-(DL-lactide-co-glycolide) submicron sphere prepared by solvent/non-solvent chemical methods and centrifugal processing. AB - Fine particles made of poly(lactide-co-glycolide) (DLPLG) are excellent candidates for controlled release of delivering drugs and genes, because of their degradable nature. The preparation of DLPLG submicron spheres poses serious challenges that are not necessarily present when preparing macroparticles. In the present paper, DLPLG powder is produced with chemical method using solvent/non solvent systems with subsequent centrifugation of the solution. The samples were characterized by infrared spectroscopy (IR), scanning electron microscopy (SEM) and stereological analysis. By changing the aging time with non-solvent and time and velocity of the centrifugal processing, it is possible to influence on the morphology and uniformity of the copolymer particles. Powder of the series with short aging time with non-solvent and longest time and velocity of the centrifugal processing has smallest particles and highest uniformity, where mean particles sizes were between 150 nm and 230 nm depending on which stereological parameters are considered (D(max), maximal diameters, feret X or feret Y). PMID- 17277971 TI - Corrosion resistance studies on grain-boundary etched drug-eluting stents. AB - In this paper we compare the influence of different microstructures on the corrosion resistance of new drug-eluting stainless steel stents, which have been produced by grain-boundary-selective electrochemical etching processes. The morphology of the stent surfaces was analysed by scanning electron microscopy (SEM), and the surface composition was investigated with Auger electron spectroscopy (AES) as well as with energy dispersive X-ray analysis (EDX). The passivity of the different microstructured stents was studied by cyclovoltammetry in Ringer solution. Release of nickel and chromium was assessed after potentiostatic experiments in Ringer solution by analysing the collected electrolyte with AAS. For stents produced by different two-step etching procedures bringing about ideal morphologies regarding the mechanical and biological properties of the surface, no significant differences in the passivation behaviour could be observed. A two-step process using first nitric acid and oxalic acid in a second step produces stent surfaces with very good corrosion properties: electrochemical analysis shows that the range of stable passivity is the same as for conventional stent surfaces, and low rates of nickel and chromium release are observed. The etching procedures do not seem to change the surface oxide layer composition. PMID- 17277973 TI - Studies of P(L/D)LA 96/4 non-woven scaffolds and fibres; properties, wettability and cell spreading before and after intrusive treatment methods. AB - Poly(L/D)lactide 96/4 fibres with diameters of 50 and 80 microm were produced. The smaller diameter fibres were carded and needle punched to form a non-woven mat. Fibres and non-woven mats were hydrolysed for a period of 20 weeks. Fibres and pressed non-woven discs were treated with low-temperature oxygen plasma and alkaline KOH hydrolysis and ethanol washing was used as a reference treatment. The non-wovens lost 50% of their tear strength after 8 weeks in vitro while the fibres still retained 65% tensile strength after 20 weeks. Hydrolysation time in KOH, treatment time and power settings of the oxygen plasma were all directly proportional to the mechanical properties of the fibres. Increasing time (and power) resulted in lower tensile properties. Rapid wetting of the scaffolds was achieved by oxygen plasma, KOH hydrolysation and ethanol washing. Cell culturing using fibroblast cell line was carried out for the treated and non-treated non woven scaffolds. In terms of adhesion and the spreading of the cells into the scaffold, best results after 3-day culturing were obtained for the oxygen plasma treated scaffolds. PMID- 17277972 TI - Premixed macroporous calcium phosphate cement scaffold. AB - Calcium phosphate cement (CPC) sets in situ to form resorbable hydroxyapatite and is promising for orthopaedic applications. However, it requires on-site powder liquid mixing during surgery, which prolongs surgical time and raises concerns of inhomogeneous mixing. The objective of this study was to develop a premixed CPC scaffold with macropores suitable for tissue ingrowth. To avoid the on-site powder-liquid mixing, the CPC paste was mixed in advance and did not set in storage; it set only after placement in a physiological solution. Using 30% and 40% mass fractions of mannitol porogen, the premixed CPC scaffold with fibers had flexural strength (mean +/- sd; n = 5) of (3.9 +/- 1.4) MPa and (1.8 +/- 0.8) MPa, respectively. The scaffold porosity reached (68.6 +/- 0.7)% and (74.7 +/- 1.2)%, respectively. Osteoblast cells colonized in the surface macropores of the scaffold and attached to the hydroxyapatite crystals. Cell viability values for the premixed CPC scaffold was not significantly different from that of a conventional non-premixed CPC known to be biocompatible (P > 0.1). In conclusion, using fast-dissolving porogen and slow-dissolving fibers, a premixed macroporous CPC scaffold was developed with strength approaching the reported strengths of sintered porous hydroxyapatite implants and cancellous bone, and non-cytotoxicity similar to a biocompatible non-premixed CPC. PMID- 17277974 TI - Increase of the final setting time of brushite cements by using chondroitin 4 sulfate and silica gel. AB - Chondroitin 4-sulfate (C4S) is a bioactive glycosaminoglycan with inductive properties in bone and tissue regeneration. Dicalcium phosphate dehydrate cements (known as brushite) are biocompatible and resorbable materials used in bone and dental surgery. In this study we analyzed the effect of C4S on the setting of a calcium phosphate cement and the properties of the resulting material. Brushite based cement powder was synthesised by mixing monocalcium phosphate with beta tricalcium phosphate and sodium pyrophosphate. When the concentration of C4S, in the liquid added to the cement powder, was between 1 and 8% the cement final setting time increases. Furthermore, the cement diametral tensile strength remains unaffected when solutions with concentrations of C4S below 5% were used, but decreases at higher C4S concentrations. Calorimetric analysis showed that the cements prepared with C4S alone and in combination with silica gel have a greater content of hydrated water. We concluded from our study that the addition of small amounts of C4S increases the cement setting time without affecting its diametral tensile strength and at the same time improves the cement's hydrophilicity. PMID- 17277975 TI - In situ study on the curing process of calcium phosphate bone cement. AB - The aim of this study was to follow the entire curing process of modified alpha TCP cement, and to explore how the liquid phase affects the curing reaction. Two calcium phosphate bone cements (CPCs) with a variety of aqueous solution were studied for comparison. In situ X-ray diffraction analysis and pH testing were employed to follow the chemical reaction, while quantitative ultrasonic measurement (QUS) was carried out to monitor the physical change. Results showed that CPC powders were completely consumed after 72 h. Two steps were presented in apatite formation. The first step was the precipitation of carbonated hydroxyapatite (CHA), and in the second step, conversion of calcium deficient hydroxyapatite (CDHA) was the dominant reaction. Finally, CPCs were fully converted to apatite except the cement with NaH2PO4 as liquid phase, because acidic environment inhibited the conversion of apatite. The pH increased linearly after mixing, when supersaturation was reached, it decreased to pH approximately 6.0 gradually. Ultrasound measurement indicated that the variation of speed of sound (SOS) was related to both apatite formation and microstructural evolution. Ultrasonic attenuation coefficient (UAC) was able to quantitatively describe the curing process from viscous paste to elastic solid as a function of curing time. Moreover, the curing reaction conformed to classical dissolution-precipitation mechanism. PMID- 17277976 TI - Age-related changes in ac-impedance spectroscopy studies of normal human dentine. AB - Non-destructive methods, such as the ac-impedance technique, have recently been applied to early caries detection and to identify micro-leakage between tooth structure and filling materials. However, in vitro impedance measurements are affected by a number of external factors. The purpose of present study was to investigate the effect of the age of teeth on impedance measurements of human dentine by employing electrical impedance spectroscopy (EIS). Fully hydrated dentine samples were prepared from extracted third molars of 20 and 50 year old patients. Ac-impedance measurements were carried out over a wide frequency range. Impedance measurements showed that there were differences in impedance between young and older dentine. In their circuit models, both resistance and capacitance were found to be significantly different (p < 0.05) for the two age groups. One of the age-related changes in dentine is the formation of peritubular dentine on the inner walls of dentinal tubules and we propose that this is responsible for the differences in impedance. Sample or patient age therefore must be considered when making impedance measurements on any tooth. PMID- 17277978 TI - Surface modification of organic polymers with bioactive titanium oxide without the aid of a silane-coupling agent. AB - Polyethylene (PE), polyethylene terephthalate (PET), ethylene-vinyl alcohol copolymer (EVOH), and poly(epsilon-caprolactam) (Nylon 6) were successfully modified with a thin crystalline titanium oxide layer on their surfaces by a simple dipping into a titanium alkoxide solution and a subsequent soak in hot HCl solution, without the aid of a silane-coupling agent. The surface modified polymers formed a bone-like apatite layer in a simulated body fluid (SBF) within a period of 2 days. PE, PET, and Nylon 6 formed an apatite layer faster and had a higher adhesive strength to the apatite. Three-dimensional fabrics with open spaces in various sizes containing such surface modified polymer fibers are expected to be useful as bone substitutes, since they may be able to form apatite on their constituent fibers in the living body, and thus, integrate with living bone. PMID- 17277977 TI - Dynamic fatigue and strength characterization of three ceramic materials. AB - Fracture strength and fatigue parameters of three ceramic materials submitted to dynamic fatigue were evaluated. A machinable leucite-reinforced dental ceramic, aluminum oxide, and yttria-stabilized zirconia (YSZ) were tested. The inert strength of the materials was determined in air (25 degrees C) at stressing rates of 70, 250, 400 MPa/s for Porcelain, Alumina and YSZ respectively. The data was analyzed using a two-parameter Weibull distribution. The Weibull modulus (m) and the characteristic of fracture (sigma0) parameters were determined for each material. Specimens were also tested in 3-point bending at different stressing rates in distilled/deionized water at 37 degrees C (dynamic fatigue) in order to calculate the fatigue parameters n and ln B. The strength for each material was characterized using Strength-Probability-Time (SPT) diagrams for 1 day, 1 year and 10 years. YSZ showed a high-fracture strength sigma0 (1,459 MPa) at a failure probability of 63.2% and high resistance to subcritical crack growth. YSZ and alumina showed better resistance to slow crack growth than porcelain, indicating less susceptibility to strength degradation by stress corrosion. Lifetime predictions after 10 years indicate a reduction of 50%, 36% and 29% in strength for porcelain, alumina and YSZ respectively. YSZ seems to be a very promising material for long-term dental and biomedical applications. PMID- 17277979 TI - Synthesis of triclinic calcium pyrophosphate crystals. AB - This paper presents a method for preparing crystals of triclinic calcium pyrophosphate (t-CPPD). A calcium pyrophosphate intermediate is first prepared by reaction of potassium pyrophosphate and calcium chloride. Samples of the intermediate are dissolved in hydrochloric acid and urea added. Upon heating to 95-100 degrees C, hydrolysis of the urea causes the pH to rise and t-CPPD crystallises out. Purity of the product was ascertained by chemical and physical analysis. Where large crystals are required an unstirred system is used, while smaller crystals are produced by stirring the reaction mixture. PMID- 17277980 TI - Gelatine/PLLA sponge-like scaffolds: morphological and biological characterization. AB - Biodegradable synthetic polymers such as poly(lactic acid) (PLA) are widely used to prepare scaffolds for cell transplantation and tissue growth, using different techniques set up for the purpose. However the poor hydrophilicity of these polymers represents the main limitation to their use as scaffolds because it causes a low affinity for the cells. An effective way to solve this problem could be represented by the addition of biopolymers that are in general highly hydrophilic. The present work concerns porous biodegradable sponge-like systems based on poly(L-lactic acid) (PLLA) and gelatine. Morphology and porosity characteristics of the sponges were studied by scanning electron microscopy and mercury intrusion porosimetry respectively. Blood compatibility was investigated by bovine plasma fibrinogen (BPF) adsorption test and platelet adhesion test (PAT). The cell culture method was used in order to evaluate the ability of the matrices to work as scaffolds for tissue regeneration. The obtained results indicate that the sponges have interesting porous characteristics, good blood compatibility and above all good ability to support cell adhesion and growth. In fact viable and metabolically active animal cells were found inside the sponges after 8 weeks in culture. On this basis the systems produced seem to be good candidates as scaffolds for tissue regeneration. PMID- 17277981 TI - Analysis of rheological properties of bone cements. AB - The rheological properties of three commercially available bone cements, CMW 1, Palacos R and Cemex ISOPLASTIC, were investigated. Testing was undertaken at both 25 and 37 degrees C using an oscillating parallel plate rheometer. Results showed that the three high viscosity cements exhibited distinct differences in curing rate, with CMW 1 curing in 8.7 min, Palacos R and Cemex ISOPLASTIC in 13 min at 25 degrees C. Furthermore it was found that these curing rates were strongly temperature dependent, with curing rates being halved at 37 degrees C. By monitoring the change of viscosity with time over the entire curing process, the results showed that these cements had differing viscosity profiles and hence exhibit very different handling characteristics. However, all the cements reached the same maximum viscosity of 75 x 10(3) Pa s. Also, the change in elastic/viscous moduli and tan delta with time, show the cements changing from a viscous material to an elastic solid with a clear peak in the viscous modulus during the latter stages of curing. These results give valuable information about the changes in rheological properties for each commercial bone cement, especially during the final curing process. PMID- 17277982 TI - Fabrication of porous low crystalline calcite block by carbonation of calcium hydroxide compact. AB - Calcium carbonate (CaCO(3)) has been widely used as a bone substitute material because of its excellent tissue response and good resorbability. In this experimental study, we propose a new method obtaining porous CaCO(3) monolith for an artificial bone substitute. In the method, calcium hydroxide compacts were exposed to carbon dioxide saturated with water vapor at room temperature. Carbonation completed within 3 days and calcite was the only product. The mechanical strength of CaCO(3) monolith increased with carbonation period and molding pressure. Development of mechanical strength proceeded through two steps; the first rapid increase by bonding with calcite layer formed at the surface of calcium hydroxide particles and the latter increase by the full conversion of calcium hydroxide to calcite. The latter process was thought to be controlled by the diffusion of CO(2) through micropores in the surface calcite layer. Porosity of calcite blocks thus prepared had 36.8-48.1% depending on molding pressure between 1 MPa and 5 MPa. We concluded that the present method may be useful for the preparation of bone substitutes or the preparation of source material for bone substitutes since this method succeeded in fabricating a low-crystalline, and thus a highly reactive, porous calcite block. PMID- 17277983 TI - Apatite formation and cellular response of a novel bioactive titanium. AB - The modification of titanium and titanium alloy surface properties by chemical and electrochemical techniques has opened new possibilities to improve the bioactivity and, in general, the biological performance of the implants once in vivo. One of the main aims is the achievement of a surface oxide layer that stimulates hydroxylapatite mineralization and, also, shows osteoconductive properties once in the host. In the present study, two different bioactive surfaces have been prepared following the method purposed by the group of Kokubo and a new method, BioSpark, involving high voltage anodic polarisation and alkali etching both on surface mineralization potential. The aim of the present work was to evaluate and compare the mineralization capability and the early cell response of titanium modified with a new bioactive method and with a well-known and widely tested biomimetic treatment, both compared to non treated titanium. Physical and chemical (energy dispersion spectroscopy, thin film X-ray diffractometry) and morphological (scanning electron microscopy) characterisation of the novel surface features has been performed. Also the effect of the novel surface properties on both hydroxyapatite precipitation and early cellular response has been investigated using in vitro models. The results have shown that both treatments produce an active outer layer on titanium but do not impair cells activity and support osteoblasts processes. BioSpark showed high bioactivity and good mineral phase deposition even after early incubation time, these properties were found in Kokubo's surface as previously published. Mineralisation mechanisms of the two materials were different, and while this mechanisms was well characterised and reported for Kokubo's surface, it was still unclear for BioSpark. In this paper an explanation was given and catalytic properties of the latter surface was bound to both well known crystal titanium oxide exhibiting anatase lattice and a certain level of calcium and phosphorus doping, which promoted chemical and physical variation in anatase properties. At the same time early osteoblasts response to Kokubo's and BioSpark's surface was characterised and, no significant differences was found. PMID- 17277984 TI - Novel elastic material from collagen for tissue engineering. AB - Elastic collagen gel (e-gel) was prepared from salmon atelocollagen fibrillar gel reinforced by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) mediated cross linking (f-gel). The preparation consisted of a simple heat treatment of the f gel at 80 degrees C, in which the f-gel drastically shrank and the collagen fibril structure was deformed. The e-gel obtained showed rubber-like elasticity; its stress-strain behavior little changed through repeated stretching. The elongation at the breaking point was approximately 230%. Furthermore, normal human osteoblasts showed good attachment and proliferation on the e-gel. These results suggest its potential to be utilized for the development of tissue engineering. PMID- 17277986 TI - Biocompatibility of ultra-high molecular weight polyethylene (UHMW-PE) stabilized with alpha-tocopherol used for joint endoprostheses assessed in vitro. AB - Adding the natural antioxidant alpha-tocopherol to ultra-high molecular weight polyethylene (UHMW-PE) can remarkably delay the oxidation of hip cups made thereof. However, alpha-tocopherol is likely to undergo different chemical transformations during manufacturing and sterilization of hip cups than in human metabolism. Therefore, the biocompatibility of the putative transformation products has to be investigated. In-vitro tests with L929 mice fibroblast-cells gave no evidence for cytotoxicity. To further ensure the biocompatibility, in vitro tests with human cells were carried out in this study. Two different human cell lines, one adherent cell line, HF-SAR, and one suspension culture, GSJO, were tested on UHMW-PE-tablets (diameter: 15 mm; thickness: 2 mm; processed according to standard procedures for artificial hip-cups) with and without alpha tocopherol with respect to cell viability, proliferation and morphology by means of cell counting, WSt-1 proliferation assay and scanning electron microscopy. Similar proliferation rates were found with both polyethylene samples. Further, we found intact morphology in light and electron microscopy on each substrate. The morphologic characteristics of skin fibroblasts were not changed by any material. Normal adherence and spreading of the fibroblasts was found on controls of glass, as well as on polystyrene and on stabilized and unstabilized polyethylene. The characteristic behaviour as suspension of the GSJO cells remained unchanged. The mitochondrial activity, as studied by WST-1 cell proliferation reagent, was identical on each substrate during the whole observation period of 7 days. PMID- 17277985 TI - Short term evaluation of material blood compatibility using a microchannel array. AB - New short-term evaluation of material blood compatibility was attempted using a microchannel array with human blood under a flow condition. The microchannel array chips were made of silicon, having 8,736 microchannels of 10 microm-wide, 30 microm-long, and 4.5 microm-deep on the average, as the models of capillary blood vessels. Titanium, chromium, albumin and collagen were coated onto the chips to examine the difference of material blood compatibility and the effect of protein adsorption on it. The time for the first 100 microl portion of whole blood to pass through the channels (blood pass-through time, BPT) was measured under a pressure difference of 20 cmH2O. Simultaneously, the flow behavior of blood cells was observed by an optical microscope. The BPT tends to correlate well with the level of platelet adhesion. The highest BPT as well as platelet adhesion was observed on collagen, followed by titanium, chromium, silicon, and albumin. These results indicate that the BPT can detect the different levels of platelet adhesion and thrombus formation on microchannel surface and that the protein adsorption onto chip surface can influence BPT. We concluded that this method could be applied to evaluate initial blood compatibility of materials within several minutes in vitro. PMID- 17277988 TI - The surface modification of stainless steel and the correlation between the surface properties and protein adsorption. AB - Protein adsorption on a biomaterial surface is of great importance as it usually induces unfavorable biological cascades, with the result that much surface modification research has had to be performed in an effort to prevent this. In this study, we developed surface modification methods for stainless steel, which is a representative metal for biomedical device. The stainless steels were first smoothened to different extents by electropolishing, in order to obtain a rough or smooth surface. On these two kinds of substrates, we introduced epoxide groups to the metal surface by silanization with 3-glycidoxypropyltrimethoxysilane (GPTS). Then, various polymers such as poly(ethylene glycol) (PEG), poly(tetrahydrofuran glycol) (PTG), poly(propylene glycol) (PPG) and poly(dimethylsiloxane) (PDMS) were grafted on the silanized stainless steels. Each surface modification step was confirmed by various analytical methods. Contact angle measurement revealed that the surface hydrophilicity was controllable by polymer grafting. Root-mean-square (RMS) data of atomic force microscopy showed that surface roughness was dramatically changed by electropolishing. Based on these results, the correlation between surface properties and protein adsorption was investigated. In the protein adsorption study, we observed that all of the polymer-grafted stainless steels exhibited lower protein adsorption, when compared with bare stainless steel. Moreover, a hydrophilic and smooth surface was found to be the best of choice for decreasing the protein adsorption. PMID- 17277987 TI - The effect of low-intensity pulsed ultrasound on bone healing in SR-PLLA rod fixed experimental distal femur osteotomy in rat. AB - The effects of low-intensity pulsed ultrasound (30 mW/cm2) were investigated in experimental cancellous bone fracture healing in bioabsorbable self-reinforced poly-L-lactide (SR-PLLA) rod fixed distal femur osteotomy in rats. A transverse transcondylar osteotomy was fixed with one SR-PLLA rod in 32 male Wistar rats of the age of 20 weeks. Half of the rats had a daily 20-min ultrasound exposure for three weeks. The follow-up times were three, six, and 12 weeks. Radiographical, histological, microradiographical, oxytetracycline labeling, and histomorphometrical analyses were performed. No foreign-body reactions were noted. The biocompatibility of SR-PLLA and ultrasound was found to be good. In the radiological and histological assessments there was a slight tendency for enhanced healing in the ultrasound group at three weeks, but at six and 12 weeks no differences were observed. The histomorphometrical and oxytetracycline labeling analyses showed that ultrasound exposure had no significant effects on bone healing. The present study shows that there were no obvious findings to support the hypothesis that low-intensity pulsed ultrasound enhances bone healing in self-reinforced poly-L-lactide (SR-PLLA) rod fixed experimental metaphyseal distal femur osteotomy in rats. The observed good biocompatibility provides a safe starting-point for clinical trials on bioabsorbable fixation combined with low-intensity ultrasound. PMID- 17277989 TI - An unusual case report of small bowel Candida overgrowth as a cause of diarrhea and review of the literature. PMID- 17277990 TI - Tumor anti-angiogenic gene therapy with microencapsulated recombinant CHO cells. AB - Microencapsulation of recombinant cells is a novel promising approach to tumor therapy in which therapeutic protein is sustainable and long-term delivered by microencapsulated cells. The semi-permeable membrane of microcapsule can protect cell from host's immune rejection, increase the chemical stability of therapeutic protein and circumvent the problems of toxicity, limited half-lives and variation in circulating levels. Endostatin, a potent and specific angiogenesis inhibitor, could suppress the growth of primary and metastatic lesions in multiple murine tumor models. In this paper, APA microcapsules with high strength kept intact over 35 days and recombinant CHO cells kept the rapid proliferation viability and the continuous endostatin-expression function. The study of tumor treatment showed that the implantation of microencapsulated recombinant CHO cells decreased the neovascularization of tumor tissue by 59.4% and inhibited the B16 melanoma growth by 77.4%. Twenty days after tumor cell injection, 80% of animals treated with microencapsulated CHO-endo cells were alive compared to only 50% of animals in either control or mock control groups. Therefore, continuous delivery of endostatin from microencapsulated recombinant cells represents a feasible approach to tumor therapy. PMID- 17277991 TI - Protein transport to choroid and retina following periocular injection: theoretical and experimental study. AB - Ocular neovascularization is a major cause of blindness in several diseases including age-related macular degeneration (choroidal neovascularization) and diabetic retinopathy (retinal neovascularization). Antiangiogenic agents with clinically significant effects exist, but a key question remains: how to effectively deliver drugs to the site of neovascularization. Periocular delivery of drugs or proteins is less invasive and safer than intravitreous delivery, but little is known regarding how and to what extent agents access intraocular tissues after periocular injection. We present a computational model of drug or protein transport into the eye following periocular injection to quantify movement of macromolecules across the sclera of the mouse eye. We apply this model to the movement of green fluorescent protein (GFP) across the mouse eye and fit the results of in vivo experiments to find transport parameters. Using these parameters, the model gives the profile of interstitial GFP concentration across the sclera, choroid and retina. We compare this to predictions of transport following intravitreous injections. We then scale up the model to estimate the transport of GFP into the human choroid and retina; the thicker sclera decreases transscleral delivery. This is the first model of ocular drug delivery to explicitly account for transport properties of each eye layer. PMID- 17277992 TI - Characterization of the practice and attitudes of genetic counselors with doctoral degrees. AB - Potential advantages and disadvantages of doctoral training in genetic counseling have been debated. In this study, individual interviews were conducted to characterize the practice and attitudes of genetic counselors who have achieved doctoral degrees in any field. Participants (N=31) were more likely to spend time in research and less likely to spend time in clinic than genetic counselors in general. Advantages identified by participants were consistent with theorized advantages, and included increased knowledge, wider research roles, additional opportunities and greater respect. Disadvantages identified by participants focused more on individual perspectives than previously theorized profession-wide disadvantages. These included increased time commitment and decreased patient contact. The attitudes of participants towards the development of doctoral training in genetic counseling were generally positive. The results suggest that doctoral training in genetic counseling would have more benefits than drawbacks for individuals pursuing this degree. PMID- 17277993 TI - Assessing the informational needs of adolescents with a genetic condition: what do they want to know? AB - Adolescence is a period of challenges that can be more stressful for someone with a genetic condition. The purpose of this descriptive pilot study was to assess the informational needs of adolescents with a genetic condition. To our knowledge, this is the first study that has attempted to identify these needs. A convenience sample of adolescents between 12-19 years of age with either phenylketonuria or congenital adrenal hyperplasia and who had not previously received genetic counseling was recruited. Recruitment ended once the themes were saturated (n=17). A twenty item open/close-ended questionnaire was used to assess participants' knowledge of their genetic condition, what they wanted to know about their condition and in what manner. Almost all of the adolescents knew the name and genetic basis of their condition while most were aware of the risk of recurrence in a future pregnancy. Parents and doctors respectively, were identified as the primary and secondary sources of genetic information. Despite their evolving independence, almost all of the participants favoured receiving medical information with their parents present. The majority of participants felt that patients should begin receiving genetic information before the age of 12 years. Thematic analysis revealed that adolescents wanted to understand the science behind their condition, how their condition affects them, and how to manage it. The results highlight (i) the importance that adolescents place on parental involvement in their medical care (ii) that adolescents would like information about the genetics of their condition at a much younger age than when they usually receive genetic counseling and (iii) the benefits that can be gained by this patient population from receiving genetic counseling. PMID- 17277994 TI - The effect of disruptions during counseling on recall of genetic risk information: the case of cystic fibrosis. AB - Genetic counseling is a communication process with two main functions: information provision and supportive counseling. The information transmission function may be compromised by disruptions that occur during counseling. At least two mediators are possible: (a) disruptions may interfere with memory by creating distractions and divided attention during encoding or (b) disruptions may degrade the flow of interaction which requires that participants engage in conversation repair rather than the task at hand. This study examined both alternatives in a group of parents (N=20 families, 40 individual parents) whose infant had received a newborn screening for cystic fibrosis (CF). Upon arrival at the hospital, each parent completed a questionnaire designed to assess his or her knowledge of CF. Their interaction with the genetic counselor was videotaped and coded for the presence of disruptions. Six weeks after the counseling, parents again completed the knowledge measure. The data showed a direct negative effect for disruptions during counseling on memory for CF-related risk information six weeks later. Disruptions also produced the anticipated effect on conversation, but counter to expectations, interruptions of conversation flow was positively associated with knowledge at time 2. PMID- 17277995 TI - Increasing utilization of cancer genetic counseling services using a patient navigator model. AB - Rarely has utilization of genetic counseling for Hereditary Breast and Ovarian Cancer (HBOC) been studied separately from utilization of testing. At Kaiser Permanente Colorado, consistently only 30% of all members referred for HBOC attend genetic counseling. To increase the volume of genetic counseling appointments, a patient navigator approach was pilot tested in a randomized controlled trial over 3 months. A total of 125 members were referred for HBOC genetic counseling (55 randomized to PN, 70 randomized to usual care). Utilization of referrals for Navigator-assisted members was 44%, compared to 31% in the usual care arm (p=0.16). The patient navigator significantly decreased time to appointment, with over 80% of Navigator-assisted members seen for genetic counseling less than three months from referral date, compared to 32% in usual care (p=0.002). patient navigator assistance shortens time from referral to appointment for HBOC genetic counseling, and may increase utilization of such services. PMID- 17277996 TI - Living with multiple endocrine neoplasia type 1: decent care-insufficient medical and genetic information: a qualitative study of MEN 1 patients in a Swedish hospital. AB - This qualitative study explores how 29 Swedish patients with Multiple Endocrine Neoplasia type 1 (MEN1) experience living with the condition, appraisal of the clinical follow-up program, and surveys their future expectations. The aim of this study is to build knowledge about this patient group in order to provide optimal care. The participants describe physical, psychological, and social limitations in their daily activities and how these limitations influence quality of life. Our findings indicate that a majority of patients have adjusted to their situation, describing themselves as being healthy despite physical symptoms and treatment. The participants received decent care in the clinical follow-up program, - however, greater effort should be put into patient information. These patients might benefit from genetic counseling. Health professionals involved should recognize their potential impact and influence on a patient's ability to adjust to these circumstances. Antonovsky's Sense of Coherence theory is used to discuss these findings. PMID- 17277997 TI - Spiritual assessment in genetic counseling. AB - One hundred and twenty seven full members of the National Society of Genetic Counselors participated in this study exploring current spiritual assessment practices of genetic counselors and reactions to a spiritual assessment tool. While 60% of genetic counselors reported they had performed a spiritual assessment within the past year, fewer than 8.7% of these counselors assessed spirituality in more than half of their sessions. Counselors reporting high perceived relevance of spiritual assessment performed an assessment more frequently than those reporting a low perceived relevance. Barriers to spiritual assessment included lack of time, insufficient skills, and uncertainty regarding the role of spiritual assessment within genetic counseling. Almost two-thirds of counselors expressed that having a spiritual assessment tool would increase their ability to elicit relevant information. These data suggest a need for increased training regarding the methods for and relevance of spiritual assessment in genetic counseling. Recommendations for future directions of research are explored. PMID- 17277999 TI - Off-target properties of pharmacotherapy and the importance of mechanistic investigations in early clinical phase drug development. PMID- 17277998 TI - Response to aspirin and clopidogrel in patients scheduled to undergo cardiovascular surgery. AB - BACKGROUND: Recent data indicate that among patients undergoing percutaneous coronary intervention low platelet response to aspirin is associated with clopidogrel low response. It is unclear whether these findings extend to other patient populations. We, therefore, aimed to evaluate the relation between response to aspirin and clopidogrel among patients scheduled to undergo cardiac or vascular surgery. METHODS: Patients who were scheduled for cardiac or vascular surgery and had taken aspirin 81-325 mg daily for at least a week and clopidogrel 75 mg daily for at least 3 days underwent blood testing for platelet function. One hundred patients were included in the current analysis. Platelet function was evaluated by the modified TEG platelet mapping assay with addition of ADP or arachidonic acid (AA), and by the PFA-100 assay with collagen-epinephrine (CEPI) or collagen-ADP (CADP) cartridges. Low response to aspirin or clopidogrel was defined as inhibition < or =20% for TEG-AA or TEG-ADP, respectively. RESULTS: Thirteen patients (13%) were low responders to aspirin and 34 (34%) were low responders to clopidogrel. Eight patients were low responders to both drugs. There were no differences in clinical characteristics between drug low responders versus sensitive patients. Aspirin low responders had lower TEG-ADP inhibition (19.5 +/- 6 vs. 35.8 +/- 3%, P = 0.03) and tended to have lower PFA-CADP time (84.7 +/- 7 vs. 105.6 +/- 5 s, P = 0.1) than aspirin sensitive patients. Clopidogrel low responders had lower TEG-AA inhibition (58 +/- 6 vs. 75.1 +/- 4%, P = 0.01) and PFA-CEPI time (168 +/- 13 vs. 200.4 +/- 10 s, P = 0.07) than clopidogrel sensitive patients. CONCLUSIONS: In patients scheduled to undergo cardiovascular surgery low response to aspirin is associated with low response to clopidogrel. PMID- 17278002 TI - Calreticulin: raising awareness of apoptosis. PMID- 17278000 TI - A dose-finding clinical trial of staphylokinase SY162 in patients with long-term venous access catheter thrombotic occlusion. AB - BACKGROUND: We investigated the safety and efficacy of several dosing regimens of catheter-directed staphylokinase (SY162) bolus administration for the treatment of long-term venous access catheter occlusion. METHODS: This open-label, ascending dose study enrolled 24 subjects. Three doses of SY162 were evaluated in three cohorts (0.15 mg, 0.3 mg and 0.45 mg) with eight subjects each. Catheter function was evaluated 30 min after the first bolus administration. In case of incomplete catheter function restoration, a second bolus was administered with reassessment of catheter function 30 min thereafter. Cathetergram was repeated to assess thrombus resolution. RESULTS: Complete restoration of catheter withdrawal function was observed in 2 (25%), 1 (13%) and 7 (88%) subjects after the first bolus in the first, second and third cohort respectively and in 4 (50%), 7 (88%) and 7 (88%) patients after the second administration of SY162. There were no bleeding complications nor other adverse events related to SY162. CONCLUSIONS: The doses tested in this trial were well tolerated and safe. A dose-response effect within the dose range tested was observed. A 2 ml bolus injection of 0.45 mg SY162 resulted in optimal efficacy after 30 min. PMID- 17278004 TI - Cohort studies of etiology and survival after cancer: the unique needs for uninterrupted funding. AB - The existing prospective cohorts are providing key data that are guiding public health and clinical practice in many different areas. The existing cohorts can also provide the biological specimens and data to address genetic determinant of cancer now, rather than in a decade, and at far less cost than that proposed for a new national U.S. cohort. Review and funding mechanisms are needed to avoid disruption in follow-up and the associated damage to existing cohorts. PMID- 17278005 TI - Effects of Cadmium (CdCl(2)) on development and hatching of eggs in European squid (Loligo vulgaris Lamarck, 1798) (Cephalopoda: Loliginidae). AB - This is the first study related to the effects of cadmium (Cd) on the development and hatching of eggs of Loligo vulgaris. The eggs were exposed to concentrations varying from 10 to 100,000 microg Cd/l for up to 1 month. During the study period natural sea water salinity (37 PSU), ambient temperature (ranging 16.5-21.5 degrees C) and light conditions of 12-h light: 12-h dark for 744-h were used prior to the hatching. For 96-h, mortality rate of 100% of the eggs was found at cadmium concentration of 100,000 microg Cd/l, and the same mortality rate of the eggs were found at 1,000 and 10,000 microg Cd/l for 744-h and 696-h, respectively. Hatching took place between hours 456 and 576 in the control group and between hours 480 and 576 in 10 and 100 microg Cd/l groups. Total hatching rates were calculated to be 98.2 +/- 1.6% for control group, 99.4 +/- 0.6% for 10 microg Cd/l group and 98.6 +/- 1.2% for 100 microg Cd/l group. Hatching successes were estimated as 69.5 +/- 13.8% for control group, 84.5 +/- 8.2% for 10 microg Cd/l group and 76.9 +/- 5.9% for 100 microg Cd/l group. In the 100,000 microg Cd/l treatment, the egg degeneration began from animal pole of the eggs in 16 h, and 50% and 100% of them died in the initial stage at 72-h and 96-h, respectively. In the 10,000 microg Cd/l group, the eggs which reached at stage 19 (IX) were deformed and 50% and 100% of them died at 312-h and 696-h, respectively. In 1,000 microg Cd/l group, however, the eggs developed abnormally from stage 21 (X-XI) and reached at stage 29 (XIX), and 50% and 100% of them died in 624-h and in 744-h, respectively. There were significant differences in survival rates of the eggs among the concentrations (p < 0.05). The current study demonstrated that Cd adversely affects the development, survival and hatching of L. vulgaris eggs; however, no mortality was observed in 10 microg Cd/l and 100 microg Cd/l groups. PMID- 17278006 TI - A classification of U.S. estuaries based on physical and hydrologic attributes. AB - A classification of U.S. estuaries is presented based on estuarine characteristics that have been identified as important for quantifying stressor response relationships in coastal systems. Estuaries within a class have similar physical and hydrologic characteristics and would be expected to demonstrate similar biological responses to stressor loads from the adjacent watersheds. Nine classes of estuaries were identified by applying cluster analysis to a database for 138 U.S. estuarine drainage areas. The database included physical measures of estuarine areas, depth and volume, as well as hydrologic parameters (i.e., tide height, tidal prism volume, freshwater inflow rates, salinity, and temperature). The ability of an estuary to dilute or flush pollutants can be estimated using physical and hydrologic properties such as volume, bathymetry, freshwater inflow and tidal exchange rates which influence residence time and affect pollutant loading rates. Thus, physical and hydrologic characteristics can be used to estimate the susceptibility of estuaries to pollutant effects. This classification of estuaries can be used by natural resource managers to describe and inventory coastal systems, understand stressor impacts, predict which systems are most sensitive to stressors, and manage and protect coastal resources. PMID- 17278007 TI - Quantification of the impact of land-use changes on ecosystem services: a case study in Pingbian County, China. AB - Pingbian Miao Autonomous County is one of the poorest rural areas in China. Land use changes, mainly driven by agricultural expansion and deforestation, may significantly impact ecosystem services and functions, but such effects are difficult to quantify. In the present study, Landsat image data were combined with the published coefficients about the world and China ecosystem to quantify land-use and ecosystem service changes in the mountainous area. A sensitivity analysis was employed to determine the effect of manipulating these coefficients on the estimated values. Our results show that during the past decades (from 1973 to 2004) forests and grasslands were converted into shrubland and cropland, respectively, resulting in a continuous decrease in ecosystem service (from 124.5 US$ x 10(6) in 1973 to 100.4 US$ x 10(6) in 2004). We found that the decrease of mixed forest in the study area was the largest contributor (i.e., 25.4 US$ x 10(6)) to the decline of the ecosystem service. Therefore we propose that future land-use policy should pay more attention to the crucial ecosystem functions of these forests (including tropical forest), and that it is necessary to balance the relationship between the livelihood of local farmers and environmental protection in order to maintain a healthy and stable ecosystem. PMID- 17278008 TI - Physico-chemical characteristics of some waters used for drinking and domestic purposes in the Niger Delta, Nigeria. AB - Physico-chemical characteristics of some river and hand-dug well waters used for drinking and domestic purposes in the oil rich Niger Delta area of Nigeria were assessed using standard methods. The concentrations of the parameters in the river water samples ranged in the following order: pH (5.6-6.9), temperature (26.90-28.60 degrees C), turbidity (23-63 NTU), electrical conductivity (52-184 mus/cm), DO (5.4-7.2 mg/l), BOD (21-57 mg/l), TDS (6.0-217 mg/l), PO4 (3-) (0.19 1.72 mg/l), SO4 (2-) (25-36.8 mg/l), NO3 (-) (20.3-28 mg/l), Fe (6.07-15.71 mg/l), Zn (0.04-0.24 mg/l), Pb (0.01-0.17 mg/l), Ni (0.01-0.13 mg/l), Vn (0.01 0.20 mg/l) and Hg (0.001-0.002 mg/l). The concentrations of these parameters in the hand-dug well water ranged in the following order: pH (5.7-6.8) temperature (26-30 degrees C), turbidity (134-171 NTU), electrical conductivity (160-340 mus/cm), DO (5.4-6.4 mg/l), BOD (13-34 mg/l), TDS (110-190 mg/l), PO(4) (3-) (0.84-1.84 mg/l), SO4 (2-) (10.6-28.1 mg/l), NO3 (-) (11.3-23 mg/l), Fe (13.17 16.31 mg/l), Ni (0.01-0.02 mg/l), Vn (0.01-0.04 mg/l) and Hg (0.001-0.004 mg/l). The concentrations of BOD, turbidity, NO3 (-) and Fe in the water samples were above WHO and FMENV permissible limits for safe drinking water. The results suggest that the use of such waters for drinking and domestic purposes pose a serious threat to the health of the users and calls for the intervention of government agencies. PMID- 17278011 TI - Beta-1 adrenergic receptor antisense-oligodeoxynucleotides ameliorates left ventricular remodeling in 2-Kidney, 1-Clip rats. AB - Gene therapy has been applied to reduce blood pressure in rats. However, little is known about the effects of gene therapy on both blood pressure and left ventricular (LV) remodeling. This study was designed to compare the antihypertensive effect of ss(1) adrenergic receptor antisense oligodeoxynucleotides (ss(1)- AS-ODN) by delivery with the different charge ratios cationic liposomes DOTAP/DOPE and its impact on the LV remodeling in rats with 2-Kidney, 1-Clip (2K1C) Hypertension. Five charge ratios of liposome/ODN were tested in 2K1C rats. There was hypertension, cardiac dysfunction, LV hypertrophy and LV collagen deposition in 2K1C rats. On the basis of the magnitude and duration of hypotension, 2.0 was determined to be the optimal charge ratio, which decreased blood pressure by up to 39 mm Hg for 27 days. ss(1) AS-ODN preserved cardiac function and inhibited LV mass and LV interstitial collagen deposition. In conclusion, cationic liposomes DOTAP/DOPE improve the antihypertensive effects of ss(1)-AS-ODN in renovascular hypertension and 2.0 were determined to be the optimal charge ratio. This study demonstrated that cardiac ss(1)-AR played a key role in LV remodeling and ss1-AS-ODN ameliorates cardiac dysfunction and LV remodeling. PMID- 17278010 TI - Amelioration of beryllium induced alterations in hepatorenal biochemistry and ultramorphology by co-administration of tiferron and adjuvants. AB - Influence of adjuvants i.e., alpha-tocopherol (25 mg/kg, p.o.) and piperine (10 mg/kg, p.o.) on therapeutic potential of chelator tiferron (300 mg/kg, i.p.) was evaluated to encounter toxicogenic events of beryllium exposure. Albino rats were exposed to beryllium nitrate (1 mg/kg, i.p.) daily for 28 days followed by treatment of aforesaid therapeutic agents for 5 consecutive days. Results were considered to be significant at p < or =0.01 and p < or =0.05. Exposure to beryllium increased its concentration in liver, kidney and serum causing significant alterations in the activity of CYP-450 2E1 system, microsomal lipid peroxidation and protein; alkaline phosphtase, lactate dehydrogenase, gamma glutamyl transpeptidase, bilirubin, creatinine and urea in serum; activity of acid phosphatase, alkaline phosphatase, adenosine triphosphatase, glucose-6 phosphatase and succinic dehydrogenase in liver and kidney. Beryllium exposure also induced severe alterations in histopathology and ultramorphology of liver and kidney proving its toxic consequences at cellular level. Tiferron along with adjuvants dramatically reversed alterations of all variables more towards control rather than individual treatment. Study concluded that tiferron in combination with alpha-tocopherol and piperine respectively was beneficial in diluting beryllium induced systemic toxicity; however, combination of tiferron and piperine presented more pronounced therapeutic potential. PMID- 17278009 TI - Kelp as a bioindicator: does it matter which part of 5 m long plant is used for metal analysis? AB - Kelp may be useful as a bioindicator because they are primary producers that are eaten by higher trophic level organisms, including people and livestock. Often when kelp or other algae species are used as bioindicators, the whole organism is homogenized. However, some kelp can be over 25 m long from their holdfast to the tip of the blade, making it important to understand how contaminant levels vary throughout the plant. We compared the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in five different parts of the kelp Alaria nana to examine the variability of metal distribution. To be useful as a bioindicator, it is critical to know whether levels are constant throughout the kelp, or which part is the highest accumulator. Kelp were collected on Adak Island in the Aleutian Chain of Alaska from the Adak Harbor and Clam Cove, which opens onto the Bering Sea. In addition to determining if the levels differ in different parts of the kelp, we wanted to determine whether there were locational or size-related differences. Regression models indicated that between 14% and 43% of the variation in the levels of arsenic, cadmium, chromium, manganese, mercury, and selenium was explained by total length, part of the plant, and location (but not for lead). The main contributors to variability were length (for arsenic and selenium), location (mercury), and part of the plant (for arsenic, cadmium, chromium and manganese). The higher levels of selenium occurred at Clam Cove, while mercury was higher at the harbor. Where there was a significant difference among parts, the holdfast had the highest levels, although the differences were not great. These data indicate that consistency should be applied in selecting the part of kelp (and the length) to be used as a bioindicator. While any part of Alaria could be collected for some metals, for arsenic, cadmium, chromium, and manganese a conversion should be made among parts. In the Aleutians the holdfast can be perennial while the blade, whipped to pieces by winter wave action, is regrown each year. Thus the holdfast may be used for longer-term exposure for arsenic, cadmium, chromium and manganese, while the blade can be used for short term exposure for all metals. Cadmium, lead and selenium were at levels that suggest that predators, including people, may be at risk from consuming Alaria. More attention should be devoted to heavy metal levels in kelp and other algae from Adak, particularly where they may play a role in a subsistence diets. PMID- 17278012 TI - Tachyphylaxis to the inhibitory effect of L-type channel blockers on ACh-induced [Ca2+]i oscillations in porcine tracheal myocytes. AB - Discrepancies about the role of L-type voltage-gated calcium channels (VGCC) in acetylcholine (ACh)-induced [Ca(2+)](i) oscillations in tracheal smooth muscle cells (TSMCs) have been seen in recent reports. We demonstrate here that ACh induced [Ca(2+)](i) oscillations in TMCS were reversibly inhibited by three VGCC blockers, nicardipine, nifedipine and verapamil. Prolonged (several minutes) application of VGCC blockers, led to tachyphylaxis; that is, [Ca(2+)](i) oscillations resumed, but at a lower frequency. Brief (15-30 s) removal of VGCC blockers re-sensitized [Ca(2+)](i) oscillations to inhibition by the agents. Calcium oscillations tolerant to VGCC blockers were abolished by KB-R7943, an inhibitor of the reverse mode of Na(+)/Ca(2+) exchanger (NCX). KB-R7943 alone also abolished ACh-induced [Ca(2+)](i) oscillations. Enhancement of the reverse mode of NCX via removing extracellular Na(+) reversed inhibition of ACh-induced [Ca(2+)](i) oscillations by VGCC blockers. Inhibition of non-selective cation channels using Gd(3+) slightly reduced the frequency of ACh-induced [Ca(2+)](i) oscillations, but did not prevent the occurrence of tachyphylaxis. Altogether, these results suggest that VGCC and the reverse mode of NCX are two primary Ca(2+) entry pathways for maintaining ACh-induced [Ca(2+)](i) oscillations in TSMCs. The two pathways complement each other, and may account for tachyphylaxis of ACh-induced [Ca(2+)](i) oscillations to VGCC blockers. PMID- 17278013 TI - Infections and human tissue transplants: review of FDA MedWatch reports 2001 2004. AB - BACKGROUND: More than 1.5 million tissue allografts are transplanted annually in the U.S. As part of the federal effort to improve tissue safety, FDA's May 2005 Current Good Tissue Practices (CGTP) Rule requires tissue establishments to report to FDA serious infectious adverse events following allograft transplantation. To provide baseline data, we summarize reports of such infections received by FDA prior to the CGTP Rule. METHODS: We reviewed reports received by FDA's MedWatch adverse event reporting system during 2001-2004. Our case definition was a reported infection in a human tissue transplant recipient within 1 year of transplantation. We examined demographics, tissue type, clinical outcomes and interventions, infectious organism(s), time from transplant to infection and reporter characteristics. RESULTS: We identified 83 reports of infections following allograft transplantations. Median patient age was 40 years (range: 1 month-87 years). The allografts included heart valves (42%), tendons (33%), bones (8%), blood vessels (6%), ocular tissues (5%), and skin (4%). Commonly reported outcomes and interventions were hospitalization (72%), antibiotic therapy (46%) and graft removal (42%). Nine of 11 patients who expired had received heart valves. In 65 reports that identified suspected organisms, bacteria were most common (42), followed by fungi (25) and prions (1). The median time from transplant to infection was 5.5 weeks (range: 3 days-52 weeks). Tissue manufacturers submitted 26% of reports. Among the remaining 74%, the reporters were quality assurance staff, infection control or risk management personnel (45%); physicians (15%); consumers (15%); nurses (13%); and surgical staff (12%). CONCLUSION: This is the first review of reports to FDA for infections following allograft tissue transplantations. Infections led to serious outcomes and involved many tissue types. Although we were unable to confirm that reported infections were caused by the suspected tissue product, required reporting by tissue establishments and improvements in adverse event investigation will help to improve tissue safety surveillance. PMID- 17278014 TI - Down-regulation of iNOS and TNF-alpha expression by kaempferol via NF-kappaB inactivation in aged rat gingival tissues. AB - The primary objective of this study was to evaluate the ability and mechanism of action of kaempferol, which is contained in extracts from Nelumbo nucifera, a well-known Oriental herb used in traditional medicine, with regard to the inhibition of iNOS and TNF-alpha expression in aged rat gingival tissues. We conducted an investigation into the age-related effects of kaempferol on reactive oxygen species (ROS) and GSH oxidative status in samples of aged gingival tissues. Western blotting was conducted in order to determine the expression of iNOS, TNF-alpha, p38 MAPK, NIK/IKK, p65 and IkappaBalpha in the sample tissues. Electrophoretic mobility shift assays (EMSA) were conducted in an effort to characterize the binding activities of NF-kappaB transcription factors in the aged rat gingival nuclear extracts. Our results indicate that kaempferol reduced ROS levels and augmented GSH levels in a dose-dependent manner in the aged gingival tissues. Kaempferol was shown to effect a significant reduction in iNOS and TNF-alpha protein levels, as compared to control gingival tissue samples. The results of Western blot analysis revealed that kaempferol treatment effected the reduction of iNOS and TNF-alpha expression, decreased nuclear p65 and increased cytosolic p65, down-regulation of Erk, p38, JNK and NIK/IKK expression. The EMSA results also indicated that kaempferol, when administered to the rat tissues, attenuated the NF-kappaB nuclear binding activity. Kaempferol may inhibit ROS generation via the inhibition of iNOS and TNF-alpha expression in aged gingival tissues, via the modulation of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways. PMID- 17278015 TI - Efficacy and safety of iguratimod compared with placebo and salazosulfapyridine in active rheumatoid arthritis: a controlled, multicenter, double-blind, parallel group study. AB - We conducted a 28-week, randomized, double-blind, parallel-group study of iguratimod in 376 Japanese patients with active rheumatoid arthritis to compare the efficacy and safety of the drug with those of placebo and salazosulfapyridine. In the American College of Rheumatology (ACR) 20 response rate, iguratimod was superior to placebo (53.8% versus 17.2%; Fisher's exact test, P < 0.001) and was not inferior to salazosulfapyridine (63.1% versus 57.7%, 95% confidence interval for the rate difference, -7.9% to 18.7%). Iguratimod began exhibiting its therapeutic effect within 8 weeks after the initiation of treatment and was effective even in patients who had a poor response to previous treatment with disease-modifying antirheumatic drugs. No statistically significant difference was noted in the incidence of adverse reactions between iguratimod and salazosulfapyridine. The study results suggest that iguratimod could become a new option for the treatment of rheumatoid arthritis. PMID- 17278016 TI - Long-term safety study of iguratimod in patients with rheumatoid arthritis. AB - We conducted a 52-week clinical study of iguratimod in 394 Japanese patients with rheumatoid arthritis to evaluate the long-term safety of the drug. Iguratimod was administered orally at a daily dose of 25 mg for the first 4 weeks and 50 mg for the subsequent 48 weeks. Some of the patients continued the treatment for 100 weeks for their benefit. The cumulative incidence of adverse events for 100 weeks was 97.6%. The cumulative incidence of adverse reactions was 65.3%; unfavorable symptoms and signs (excluding abnormal laboratory data changes) accounted for 33.2% of the reactions, and abnormal laboratory data changes accounted for 50.4%. The continued treatment rate was 66.8% at week 28 and 53.6% at week 52. For reference, the American College of Rheumatology (ACR) 20 response rate was calculated for the patients who had assessable disease activity, who did not violate the study protocol, and who continued the study treatment at weeks 28 and 52. The rate was 46.9% at week 28 and 41.0% at week 52. To use iguratimod safely for a long time, patients should be observed closely for adverse reactions such as increased hepatic enzymes. PMID- 17278017 TI - Scientific basis for the efficacy of combined use of antirheumatic drugs against bone destruction in rheumatoid arthritis. AB - Finding a means to ameliorate and prevent bone destruction is one of the urgent issues in the treatment of rheumatoid arthritis. Recent studies revealed bone resorbing osteoclasts to be essential for arthritic bone destruction, but to date there has been scarce experimental evidence for the underlying mechanism of the bone-protective effect of antirheumatic drugs. Here we examined the effects of one or a combination of disease-modifying antirheumatic drugs (DMARDs) on osteoclast differentiation to provide a cellular and molecular basis for their efficacy against bone destruction. The effects on osteoclast precursor cells and osteoclastogenesis-supporting cells were distinguished by two in vitro osteoclast culture systems. Methotrexate (MTX), bucillamine (Buc) and salazosulphapyridine (SASP) inhibited osteoclastogenesis by acting on osteoclast precursor cells and interfering with receptor activator of NF-kappaB ligand (RANKL)-mediated induction of the nuclear factor of activated T cells (NFAT) c1. MTX and SASP also suppressed RANKL expression on osteoclastogenesis-supporting mesenchymal cells. Interestingly, the combination of three antirheumatic drugs exerted a marked inhibitory effect on osteoclastogenesis even at a low dose at which there was much less of an effect when administered individually. These results are consistent with the reported efficacy of combined DMARDs therapy in humans and suggest that osteoclast culture systems are useful tools to provide an experimental basis for the bone-protective effects of antirheumatic drugs. PMID- 17278018 TI - The serum concentration of infliximab in cases of autologous blood donation for patients with rheumatoid arthritis. AB - Our aim was to determine whether the use of infliximab for rheumatoid arthritis (RA) patients is associated with an increased rate of postoperative complications. In this study we evaluated the serum concentration of infliximab to study the influence of autologous blood donation (AB donation) in patients who were administered infliximab and underwent total knee replacement (TKR). We examined five RA patients. Infliximab combined with methotrexate was administered at 3 mg/kg every 8 weeks for all patients. We carried out the TKR operation in the middle of the 8-week interval in which infliximab was administered. The AB donation consisted of 400 ml pooled AB drawn at one point 2 weeks following the final administration of infliximab. Serum infliximab levels were measured using an enzyme-linked immunosorbent assay. Mean serum infliximab levels were 5.46 +/- 5.62 microg/ml 2 weeks after the final administration of infliximab, 2.02 +/- 1.66 microg/ml just before the operation, and 1.48 +/- 1.31 microg/ml 1 day post operation. Moreover, the mean serum level in an autologous blood bag sampled just before AB donation was 5.02 +/- 4.79 microg/ml. This study indicated the serum level of infliximab in the stored blood remained at almost the same level as the collected autologous blood. However, even after autotransfusion those levels were decreased compared with levels measured just before the operation. Therefore, we conclude that there is little influence of AB donation on the risks of infliximab. PMID- 17278019 TI - Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan (RECONFIRM). AB - This study aims to reconfirm the clinical efficacy and related factors of infliximab therapy, the first biological agent introduced to Japanese patients with rheumatoid arthritis (RA). Data of 351 RA patients with infliximab were collected retrospectively from three major centers for management of rheumatic diseases in Japan. Infliximab was infused according to the approved method, and the clinical response was evaluated following 22 weeks of infliximab therapy in 258 patients using the European League Against Rheumatism (EULAR) response criteria. DAS28-CRP (Disease Activity Score including a 28-joint count/C-reactive protein) with a threshold of 4.1 or 2.7 for the high or low disease activity cut off was also used. A total of 90.3% of patients exhibited high disease activity before infliximab therapy. After 22 weeks of infliximab therapy, the proportions of patients exhibiting high activity, moderate activity, low activity, or in clinical remission were 27.9%, 33.3%, 10.9%, or 27.9%, respectively, thereby indicating good overall efficacy of infliximab therapy. A good or moderate overall response to therapy was achieved in 84.5% of patients. Male sex, rheumatoid factor (RF) negativity, low CRP, lower swollen joint count and a low prednisolone dose were significantly related to the clinical response. Furthermore, male sex, older age, and a high tender joint count had a significant correlation with treatment discontinuation as a result of adverse reactions. In conclusion, we have reconfirmed the effectiveness of infliximab in Japanese patients with RA by using DAS28-CRP and EULAR response criteria. These data will facilitate more efficacious use of this expensive biological agent in the daily practice of rheumatology in Japan. PMID- 17278020 TI - Ten years results of bucillamine in the treatment of rheumatoid arthritis. AB - A 10-year cohort study was performed, involving all of the 118 patients treated with bucillamine in our hospital between 1988 and 1990. Evaluation was made on the basis of erythrocyte sedimentation rate, grip strength, joint score, duration of morning stiffness, and Lansbury index consisting of the above four parameters. Eleven patients were male and 107 were female, with a mean age of 53 years (range: 20-79 years) and a mean duration of illness of 8.2 years (range: 2-31 years). Lansbury index remained significantly suppressed throughout the 10-year period of treatment. Continuous treatment was possible for 10 years in 18 patients (15%: 2 men and 16 women). Stage of disease did not advance in 14 patients. Six patients met the criteria for remission. Of all patients, 50% dropped out of treatment at 2.4 years after the start of treatment and 75% at 5 years. The 100 patients who dropped out could be roughly divided into three groups. One third of them dropped out because of lack of or attenuation of response. Another third dropped out because of referral to other medical facilities or discontinuation of visits to our hospital, and the remaining third dropped out because of adverse reactions to treatment. There was no particular trend in terms of sex, age, duration of sickness, drugs used before bucillamine, or level of activity of rheumatoid arthritis. There were no significant difference in the stage and class of the disease, and other backgrounds between 10-year treatment group and dropout group. PMID- 17278021 TI - Pulmonary-renal syndrome in systemic sclerosis: a report of three cases and review of the literature. AB - We describe three cases of acute renal failure with diffuse alveolar hemorrhage, which is designated pulmonary-renal syndrome (PRS), in systemic sclerosis (SSc) and review the literature to better define this rare but severe complication of SSc. The clinical course of three SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage are reported, and the literature published between 1967 and 2005 is reviewed following a PubMed search. Including our cases, a total of 19 SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage have been reported. Pulmonary-renal syndrome developing in SSc patients can be categorized clinicopathologically into three entities: PRS with thrombotic microangiopathy, PRS with small vessel vasculitides accompanied with SSc, and d-penicillamine-induced Goodpasture-like syndrome. Patients with scleroderma PRS with thrombotic microangiopathy, to which group our all patients belong, often developed diffuse alveolar hemorrhage after receiving high-dose corticosteroid therapy. Pulmonary-renal syndrome is a fatal complication of SSc and results from different pathogenic processes. Prompt differential diagnosis between the subsets is critical, because therapeutic strategy may differ in the use of high-dose corticosteroid and plasma exchange between the subsets of PRS. Clinical courses of the patients with PRS with thrombotic microangiopathy suggest that high-dose corticosteroid therapy is a trigger of diffuse alveolar hemorrhage in patients with diffuse SSc with signs of thrombotic microangiopathy. PMID- 17278022 TI - CD40-CD40 ligand signal induces the intercellular adhesion molecule-1 expression through nuclear factor-kappa B p50 in cultured salivary gland epithelial cells from patients with Sjogren's syndrome. AB - The purpose of this study is to clarify signal transduction of expression of the intercellular adhesion molecule-1 (ICAM-1) via CD40-CD40 ligand in salivary glands of patients with Sjogren's syndrome (SS). We used cultured salivary gland epithelial cells (SG cells) from 15 SS patients and 8 controls obtained by labial minor salivary gland biopsy. First, ICAM-1 expression was determined with reverse transcriptase-polymerase chain reaction and flow cytometry in the presence or absence of soluble CD40L (sCD40L). Next, SG cells were transfected with plasmids of pGL1.3-Luc inserted with promoter region of ICAM-1, pGL1.3kB(-)-Luc mutated in nuclear factor kappa-B (NF-kappaB) binding site of pGL1.3-Luc and pNF-kappaB-Luc by lipofection method. Luciferase activity of the cells was measured in the presence or absence of sCD40L or sCD40L and an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). Finally NF-kappaB family proteins of cell nuclear extracts were determined. ICAM-1 expression was significantly enhanced with sCD40L at the mRNA and protein level. Activity of pNF-kappaB-Luc and pGL1.3-Luc was significantly elevated by stimulation with sCD40L and suppressed by PDTC. NF kappaB p50 protein level was elevated by stimulation with sCD40L and suppressed by PDTC. Our results suggest that sCD40L enhances the ICAM-1 expression by activation of NF-kappaB p50 in the SS SG cells. PMID- 17278023 TI - Bilateral ureteral stenosis and duodenal perforation in a patient with dermatomyositis. AB - We report the case of a 19-year-old man with dermatomyositis who developed abdominal pain and anuria. The examination revealed bilateral ureteral stenosis. The patient also developed multiple ulcerations of the duodenum with perforations. The clinical feature was considered to represent that of juvenile dermatomyositis, which is characterized by systemic necrotizing vasculitis. Rheumatologists should be alerted about this serious complication in patients with childhood or young adult dermatomyositis presenting with abdominal complaints. PMID- 17278024 TI - Adult T-cell lymphoma mimicking Henoch-Schonlein purpura. AB - We report a male patient with adult T-cell lymphoma, who was initially diagnosed clinically as having Henoch-Schonlein purpura (HSP) with abdominal pain and specific purpura. Adult T-cell lymphoma-like cells were minimal and abdominal lymph nodes were transiently swollen, and the symptoms were improved by supportive management. Although the clinical course was compatible with HSP, the histological examination revealed infiltration of lymphocytes rather than neutrophils. Later he developed lymphoma and was treated with chemotherapy. This rare case suggests the importance of skin biopsies to seek the underlying pathology in adult HSP. PMID- 17278026 TI - A case of SAPHO (synovitis-acne-pustulosis-hyperostosis-osteomyelitis) syndrome in which [18F]fluorodeoxyglucose positron emission tomography was useful for differentiating from multiple metastatic bone tumors. AB - We report the case of a 50-year-old Japanese woman with SAPHO (synovitis-acne pustulosis-hyperostosis-osteomyelitis) syndrome. Radiographs showed osteosclerosis of the cervical and lumbar vertebrae, as well as osteosclerosis and osteolysis of the right femoral neck, resembling multiple metastatic bony lesions. Arriving at a diagnosis required hematological and imaging tests. Whole body bone scintigraphy identified diffuse uptake from the lower cervical vertebrae to the lumbar vertebrae and marked uptake in the right femoral neck. However, with [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) scanning, abnormal [(18)F]FDG uptake was not detected in cervical and lumbar spine, or in the femoral neck. Bone biopsy showed signs of chronic nonspecific inflammation, rather than tumor or infection. Based on these findings, the patient was diagnosed with SAPHO syndrome unaccompanied by skin lesions, and administration of non-steroidal anti-inflammatory drugs provided pain relief. PMID- 17278025 TI - A case of mixed connective tissue disease complicated with thymic carcinoma and Hashimoto's thyroiditis. AB - We report the case of a 63-year-old woman who suffered from mixed connective tissue disease (MCTD) complicated with thymic carcinoma and Hashimoto's thyroiditis. Although many systemic syndromes associated with thymoma and thymic carcinoma, i.e., myasthenia gravis, pure red cell aplasia, hypogammaglobulinemia, and Hashimoto's thyroiditis, are known, this is the first report of MCTD complicated with thymic carcinoma. It was suggested that MCTD may be a paraneoplastic syndrome associated with thymic carcinoma. PMID- 17278027 TI - Leukoencephalopathy during administration of etanercept for refractory rheumatoid arthritis. AB - A 74-year-old Japanese woman was diagnosed with rheumatoid arthritis due to polyarthralgia. She was prescribed various disease-modifying anti-rheumatic drugs, but most of them were discontinued because of side effects or poor effectiveness. She was referred to our hospital in 2004, and etanercept was administered from June 2005. This resulted in rapid improvement of polyarthritis; however, she developed disorientation from February 2006. She was admitted to our hospital because of convulsions and loss of consciousness. She was diagnosed with progressive multifocal leukoencephalopathy on the basis of clinical symptoms and magnetic resonance imaging of the brain. In this significant and important case, leukoencephalopathy occurred during etanercept administration, and we refer to the risk of anti-TNFalpha drugs. PMID- 17278029 TI - HLA-B51 and cigarette smoking as risk factors for chronic progressive neurological manifestations in Behcet's disease. PMID- 17278028 TI - CD8+ T lymphocytes infiltrate predominantly in the inflammatory foci of MPO-ANCA positive thoracic hypertrophic pachymeningitis in a patient with HLA-A24. AB - Hypertrophic pachymeningitis (HP) is extremely rare and an inflammatory process that thickens the dura mater. A 59-year-old Japanese woman developed backache, became paraplegic, and magnetic resonance imaging revealed diffuse thickening of the thoracic dura mater encompassing the spinal cord. Although a test for myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) was shown to be positive, vasculitis was not found and CD8(+) T lymphocytes that predominated in the inflammatory foci. Both interleukin (IL)-2 and IL-6 were markedly elevated in not only sera but also cerebrospinal fluids, very much higher in the latter. Human leukocyte antigen (HLA) typing revealed A24 positivity, suggesting this molecule was interacting with CD8(+) T lymphocytes. It was suggested that immunological disharmony and autoimmunity would play a pivotal role in the development of HP under genetic background of HLA-A24, and HP would be one feature of multiple organ involvement in ANCA-associated diseases. PMID- 17278031 TI - The influence of angiography table shields and height on patient and angiographer irradiation during interventional radiology procedures. AB - PURPOSE: To quantify the influence of angiography table height on patient and angiographer irradiation, as compared with other routine protective measures such as the use of protective shields hanging at the tableside and from the ceiling of angiography suites. METHODS: An experimental study was carried out in which a phantom (substitute for a human body) placed on the angiography table was irradiated by pulsed fluoroscopy. Entrance exposure rates were measured at the phantom surface (surrogate of patient skin exposure by incident X-ray beam) and at 60 cm from the phantom (analog to angiographer skin exposure by scatter). Exposure rates were measured at levels corresponding to the knees, testes, waist, xyphoid appendix, shoulders, and eyes of an angiographer 178 cm tall. Measurements were repeated at angiography table heights of 85, 95, 105, and 110 cm from the floor, with and without protective shields. RESULTS: Moving the table from its highest to lowest position increased by 32% the phantom entrance exposure but decreased scatter to the angiographer. Scatter to the angiographer could be reduced most by using the protective shields (30-105 times less), but low table heights provided relatively more important protection (412-1121 muSv/hr reduction, or 15-72% scatter reduction) when shields were not used (e.g., for unprotected regions of the angiographer's body such as the hands). CONCLUSION: Working at lower table heights provides a little additional protection to exposed body parts of angiographers, at the cost of somewhat higher patient exposure. Although small, this incremental protection could be clinically relevant in the long term. The choice of table position should be a compromise based on multiple factors, including at least patient exposure, scatter to angiographers, and angiographer comfort. PMID- 17278032 TI - Subcutaneous venous port implantation in patients with bilateral breast surgery. AB - The purpose of this study was to evaluate the long-term follow-up results of subcutaneous venous ports implanted in patients with bilateral mastectomies. We retrospectively reviewed the hospital charts and the electronic database of 17 patients with bilateral mastectomies whom had venous port implantation in our interventional radiology suit. A total of 17 ports were implanted to the paramedian (n = 3) and anterolateral (standard; n = 12) chest wall, on the trapezius muscle (n = 1), and to the antecubital fossa (n = 1). The mean age was 48.29 years (range: 35-60 years). The mean time interval from time of surgery to port implantation was 34 months (range: 1-84 months). The mean follow-up time was 15 months (range: 7-39 months). Follow-up parameters and classification of the complications was defined according to the SIR guidelines. No procedure-related complication occurred. A single case of mild late infection was noted and the infection rate was 0.19/1000 catheter days. Infusion chemotherapy administration was still going on in eight patients. Two patients died during the follow-up and four patients were lost after 6 months. Port removal was performed in three patients at follow-up because of the end of treatment. One trapezius port and one paramedian port weres among the removed ports without any problem. Although we have a limited number of patients, port placement to the anterior chest wall, either paramedian or anterolateral, on the trapezius muscle or to the antecubital fossa depending on the extent of the bilateral breast surgeries that can be performed with low complication rates by a careful patient and anatomical location selection by involving the patients in the decision-making process. We believe that patient education and knowledge of possible complications have high importance in follow-up. PMID- 17278033 TI - Nucleoplasty in the treatment of lumbar diskogenic back pain: one year follow-up. AB - PURPOSE: The spine is an important source of pain and disability, affecting two thirds of adults at some time in their lives. Treatment in these patients is mainly conservative medical management, based on medication, physical therapy, behavioral management, and psychotherapy, surgery being limited to elective cases with neurologic deficits. This study was carried out to evaluate the efficacy of percutaneous nucleoplasty in patients affected by painful diskal protrusions and contained herniations. METHODS: From February 2004 to October 2005, 72 patients (48 men, 24 women; mean age 48 years) affected by lumbar disk herniation were treated with nucleoplasty coblation. All patients were evaluated clinically and with radiography and MRI in order to confirm the presence of lumbalgic and/or sciatalgic pain, in the absence of major neurologic deficit and with lack of response after 6 weeks of conservative management. RESULTS: Average preprocedural pain level for all patients was 8.2 (on a visual analog scale of 1 to 10), while the average pain level at 12 months follow-up was 4.1. At the 1 year evaluation, 79% of patients demonstrated a statistically significant improvement in numeric pain scores (p < 0.01): 17% (12 patients) were completely satisfied with complete resolution of symptoms, and 62% (43 patients) obtained a good result. CONCLUSION: Our data indicate that nucleoplasty coblation is a promising treatment option for patients with symptomatic disk protrusion and herniation who present with lumbalgic and/or sciatalgic pain, have failed conservative therapies, and are not considered candidates for open surgery. PMID- 17278034 TI - Radiological insertion and management of peritoneovenous shunt. AB - The purpose of the study was to report our experience of the management of complications following the insertion of a peritoneovenous shunt for intractable malignant ascites. From June 1999 to January 2006, 26 patients underwent insertion of a peritoneovenous shunt for ascites by interventional radiologists. We have used ultrasound and shuntography to assist in the diagnosis of the cause of shunt blockage. Successful techniques for the restoration of the shunt function include port- pumping, stripping of any fibrin sheath, and revision of either the venous or peritoneal catheter. The procedure was initially successful in all patients with continued patency until death in 17. A further four patients are still alive with a functioning shunt. There was one rapid postprocedure death resulting from pulmonary edema. Two patients developed pneumothorax, managed successfully with either a chest drain or aspiration. Shunt dysfunction occurred eight times in seven patients. There were five successful revisions in four patients. Overall, shunt patency has been maintained in 80.1% of patients. Shunt dysfunction is seen in a significant number of patients, but successful revision of the shunt can be achieved in the majority. PMID- 17278035 TI - Preoperative embolization of hypervascular Castleman's disease of the mediastinum. AB - We report the case of a 31-year-old woman with mediastinal Castleman's disease of the hyaline vascular type. This large tumor was safely resected after arterial embolization. We describe the steps of this interventional procedure and discuss related necessary precautions. PMID- 17278036 TI - Value of single-dose contrast-enhanced magnetic resonance angiography versus intraarterial digital subtraction angiography in therapy indications in abdominal and iliac arteries. AB - The objective of the study was to prove the value of single-dose contrast enhanced magnetic resonance angiography [three-dimensional (3D) ceMRA] in abdominal and iliac arteries versus the reference standard intra-arterial digital subtraction angiography (i.a.DSA) when indicating a therapy. Patients suspected of having abdominal or iliac artery stenosis were included in this study. A positive vote of the local Ethics Committe was given. After written informed consent was obtained, 37 patients were enrolled, of which 34 were available for image evaluation. Both 3D ceMRA and i.a. DSA were performed for each patient. The dosage for 3D ceMRA was 0.1 mmol/kg body weight in a 1.5-T scanner with a phased array coil. The parameters of the 3D-FLASH sequence were as follows: TR/TE 4.6/1.8 ms, effective thickness 3.5 mm, matrix 512 x 200, flip angle 30 degrees , field of view 420 mm, TA 23 s, coronal scan orientation. Totally, 476 vessel segments were evaluated for stenosis degree by two radiologists in a consensus fashion in a blinded read. For each patient, a therapy was proposed, if clinically indicated. Sensitivity, specificity, positive and negative predictive values, and accuracy for stenoses > or = 50% were 68%, 92%, 44%, 97%, and 90%, respectively. In 13/34 patients, a discrepancy was found concerning therapy decisions based on MRA findings versus therapy decisions based on the reference standard DSA. The results showed that the used MRA imaging technique of abdominal and iliac arteries is not competitive to i.a. DSA, with a high rate of misinterpretation of the MRAs resulting in incorrect therapies. PMID- 17278037 TI - Asymptomatic lumbar vertebral erosion from inferior vena cava filter perforation. AB - In 2002, a 24-year-old female trauma patient underwent prophylactic inferior vena cava filter placement. Recurrent bouts of renal stones prompted serial CT imaging in 2004. In this brief report, we describe erosion and ossification of the L3 vertebral body by a Greenfield filter strut. PMID- 17278038 TI - Radiologic variations in gastrorenal shunts and collateral veins from gastric varices in images obtained before balloon-occluded retrograde transvenous obliteration. AB - PURPOSE: To investigate variations in the features of gastrorenal shunts and collateral veins shown by balloon-occluded retrograde venography (B-RTV) and by superior mesenteric and celiac arteriography. METHODS: A retrospective analysis was performed of the variation in these features on B-RTV and arteriography images obtained from 130 patients who have undergone these studies prior to balloon-occluded retrograde transvenous obliteration at our hospital since 1993. RESULTS: At least one gastrorenal shunt was revealed in 97% (126/130) of cases. Types of gastrorenal shunts observed were as follows: only one main gastrorenal shunt, 94% (118/126) of cases; two main gastrorenal shunts with a ring-like appearance, 3% (4/126); and some gastrorenal shunts to the left renal vein, 3% (4/126). Collateral veins detected were as follows: left inferior phrenic vein, 75% (95/126) of cases; pericardiacophrenic vein, 40% (50/126); gonadal vein, 13% (16/126); retroperitoneal veins, 65% (82/126). CONCLUSION: It is very important to know the exact configuration of any gastrorenal shunts in order to guide advancement of the balloon catheter into the shunt and to avoid unexpected injection of the sclerosing agent. PMID- 17278039 TI - Spontaneous repositioning of a chest port catheter by contrast medium injection. PMID- 17278040 TI - Combination of unicuspid aortic valve, aortic coarctation, and aberrant right subclavian artery in a child: MR imaging and CTA findings. PMID- 17278041 TI - Laparoscopy-assisted distal gastrectomy with laparoscopic sentinel lymph node biopsy after endoscopic mucosal resection for early gastric cancer. AB - BACKGROUND: There has been a trend toward minimally invasive treatment of early gastric cancer. We report the preliminary results of laparoscopy-assisted distal gastrectomy with laparoscopic sentinel lymph node biopsy after endoscopic mucosal resection. METHODS: Six patients underwent laparoscopy-assisted distal gastrectomy after endoscopic mucosal resection between February 2002 and October 2005 at Mie University Hospital. These patients first underwent laparoscopic sentinel lymph node biopsy and then laparoscopy-assisted distal gastrectomy with lymphadenectomy. RESULTS: No patient underwent conversion to open surgery during the operation. None of the patients had any postoperative complications. The mean length of postoperative hospital stay was 11.3 days. Sentinel lymph nodes were identified laparoscopically in five patients. There were 20 sentinel and 85 nonsentinel lymph nodes in the six patients. Postoperatively, tissue sections showed that none of the lymph nodes were metastasized. Immunohistochemistry with D2-40 antibody showed that there were normal lymphatics in the submucosal layer with mucosal defects at the endoscopic mucosal resection site. No patients had any tumor recurrence during followup. CONCLUSIONS: Laparoscopy-assisted distal gastrectomy after endoscopic mucosal resection was a safe and curative procedure. Endoscopic mucosal resection before sentinel lymph node biopsy was acceptable for early gastric cancer. PMID- 17278043 TI - Aberrant sexual behaviours in Parkinson's disease during dopaminergic treatment. PMID- 17278042 TI - Effect of Momordica grosvenori on oxidative stress pathways in renal mitochondria of normal and alloxan-induced diabetic mice. Involvement of heme oxygenase-1. AB - BACKGROUND: Oxidative stress plays an important role in the pathogenesis of diabetes and diabetic nephropathy. Momordica grosvenori (MG), a traditional medicinal herb used as substitute sugar for obese and diabetes, exhibits anti oxidative activity in vitro. AIM OF THE STUDY: This study investigated the effect of MG on renal mitochondrial lipid peroxidation, anti-oxidative defense system, and a potent oxidative stress-responsive protein, heme oxygenase-1 (HO-1) of nondiabetic and alloxan-diabetic mice in different stages of diabetes. METHODS: Male Balb/c mice were rendered diabetic by a single intra-peritoneal injection of alloxan (200 mg/kg), while control mice received sham saline injection. Control and diabetic mice were further subdivided according to their treatments: control (saline), low dose MG (150 mg/kg) and high dose MG (300 mg/kg), which were administered immediately after confirmation of hyperglycemia by gavage daily over an 8-week period. Mice were killed by cervical dislocation at 4th and 8th week, respectively, and serum and renal tissues were harvested. Serum glucose, lipid profile and renal function were evaluated; renal homogenate were subjected to determination of malondialdehyde (MDA) and glutathione (GSH) concentration, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GSH-Px) and HO-1 activities, together with Mn-SOD and HO-1 mRNA expression; paraffin-embedded renal tissues was used for routine histopathological examination. RESULTS: Short term diabetes caused hyperglycemia and intensified oxidative stress in renal mitochondrial demonstrated by higher MDA and lower GSH levels than control group, accompanied by increased mRNA expression and activity of HO-1 and Mn-SOD, and augmented GSH-Px activity. Low dose of MG administration ameliorated hyperglycemia, inhibited HO-1 and Mn-SOD mRNA expression and reduced HO-1, Mn SOD, GSH-Px activities. Diabetic mice did not demonstrate early symptoms of diabetic nephropathy until 8th week, characterized by hyperglycemia, hyperlipidemia, and renal damage. A progressive increment in MDA level and decrease in GSH level, as well as reduced mRNA expression and activity of Mn-SOD and HO-1 in the kidney were observed. Low dose of MG attenuated diabetic nephropa thy symptoms partially, inhibited lipid peroxidation, up-regulated HO-1 and Mn SOD mRNA expression, and increased HO-1 activity. Conclusions The study confirmed the involvement of oxidative stress in the development of diabetes mediated by the pro- and antioxidant role of HO-1, and pointed to the possible anti-oxidative mechanism of the anti-diabetic and nephroprotective action of MG. PMID- 17278044 TI - 31P-MRS of skeletal muscle is not a sensitive diagnostic test for mitochondrial myopathy. AB - Clinical phenotypes of persons with mitochondrial DNA (mtDNA) mutations vary considerably. Therefore, diagnosing mitochondrial myopathy (MM) patients can be challenging and warrants diagnostic guidelines. (31)phosphorous magnetic resonance spectroscopy ((31)P-MRS) have been included as a minor diagnostic criterion for MM but the diagnostic strength of this test has not been compared with that of other commonly used diagnostic procedures for MM. To investigate this, we studied seven patients with single, large-scale deletions-, nine with point mutations of mtDNA and 14 healthy subjects, who were investigated for the following: 1) (31)P-MRS of lower arm and leg muscles before and after exercise, 2) resting and peak-exercise induced increases of plasma lactate, 3) muscle morphology and -mitochondrial enzyme activity, 4) maximal oxygen uptake (VO(2max)), 5) venous oxygen desaturation during handgrip exercise and 6) a neurological examination. All MM patients had clinical symptoms of MM, > 2% ragged red fibers in muscle, and impaired oxygen desaturation during handgrip. Fourteen of 16 patients had impaired VO(2max), 10/16 had elevated resting plasma lactate, and 10/11 that were investigated had impaired citrate synthase-corrected complex I activity. Resting PCr/P(i) ratio and leg P(i) recovery were lower in MM patients vs. healthy subjects. PCr and ATP production after exercise were similar in patients and healthy subjects. Although the specificity for MM of some (31)P MRS variables was as high as 100%, the sensitivity was low (0-63%) and the diagnostic strength of (31)P-MRS was inferior to the other diagnostic tests for MM. Thus, (31)P-MRS should not be a routine test for MM, but may be an important research tool. PMID- 17278045 TI - Hydrophobic grafted and cross-linked starch nanoparticles for drug delivery. AB - The synthesis of modified hydrophobic starch nanoparticles using long chain fatty acids was accomplished. Grafting of fatty acid on the starch was done using potassium persulphate as catalyst and the formation of graft polymer was confirmed by FTIR spectra. The thermal properties of the native and grafted starch were investigated using simultaneous TG-DTA and DSC. The graft polymerization was found to be depending on the temperature and the duration of the reaction. The modified starch nanoparticles were cross-linked with sodium tripoly phosphate for better stabilization. Morphology of the grafted starch nanoparticles was studied by SEM and AFM. Drug-loading and the controlled release of the drug from the nanoparticles was studied using indomethacin as model drug. PMID- 17278047 TI - Recurrent group A streptococcal vulvovaginitis in adult women: family epidemiology. AB - Group A beta-hemolytic streptococcal (GAS) vulvovaginitis has been reported in prepubertal girls. In adult women, a vaginal carrier state has been described, but vulvovaginitis is rarely reported. We describe 2 cases of recurrent GAS vulvovaginitis in women whose husbands were gastrointestinal carriers of GAS. Characterization of the isolated strains demonstrated that identical emm types of GAS were shared by partners. Treatment of both partners resulted in resolution of vaginitis. On the basis of negative vaginal culture results obtained after treatment of each individual episode of vaginitis, we believe that the female patients were reinfected as a result of exposure to their husbands, with shedding likely to have occurred in bed. These cases reiterate the necessity for adequate screening of the patient's family and contacts in cases of recurrent GAS infection by culturing all potential areas of GAS carriage. PMID- 17278046 TI - Effect of bioactive peptides isolated from yeastolate, lactalbumin and NZCase in the insect cell growth. AB - In this study, we have described the biological activity of various hydrolysates and its effect on cell growth, growth rate and doubling time. A potent cell culture enhancer factor was observed in the yeastolate hydrolysates, mainly in the protein fractions with low molecular weight. In this case, a growth enhancer of 60.66% was obtained. Despite a lower efficiency of crude lactalbumin hydrolysates (14%), when lactalbumin and yeastolate were added together to the culture, the cell yields were of 102%, showing a synergic effect. Nevertheless, sub fraction from LMW, of lactalbumin, obtained by Sephadex G-10 gel filtration chromatography showed a higher positive effect (23.3%) than low molecular weight fraction of lactalbumin without this chromatography step (11.3%). It is suggested that low molecular weight lactalbumin could have some inhibitory protein. On the other hand, NZCase low molecular weight showed a positive effect of 29.33%, while its sub fractions showed a negative effect of 5.5%. With these data we can suggest that these hydrolysates could be an important element to design new media, serum free, being helpful in protein recombinant production. PMID- 17278048 TI - Caspofungin in the treatment of symptomatic candiduria. AB - BACKGROUND: Because the urine concentrations achieved by echinocandin antifungal agents are low, drugs from this class are excluded from consideration when candiduria treatment is selected. METHODS: We performed a retrospective view (sponsored by Merck Research Laboratories) of case records of patients participating in phase II-III clinical studies of caspofungin to identify patients with candiduria. RESULTS: Of 12 case records collected by Merck Research Laboratories, 6 met the criteria for significant candiduria, allowing the evaluation of caspofungin therapy as judged by J.D.S. Three reported cases of candiduria secondary to hematogenous renal candidiasis were promptly eradicated. Of greater significance are 3 cases of complicated, ascending Candida glabrata infection (i.e., C. glabrata infection plus renal insufficiency), which were successfully treated with caspofungin. CONCLUSIONS: Caspofungin may have a role in treating complicated Candida urinary tract infections, especially when the infection is caused by non-albicans species of Candida. PMID- 17278049 TI - Diagnosis of coccidioidomycosis by antigen detection using cross-reaction with a Histoplasma antigen. AB - BACKGROUND: In 2005, patients with coccidioidomycosis were observed to have positive Histoplasma antigen test results. METHODS: We performed a review of the records of patients with coccidioidomycosis who were under our care who underwent testing for Histoplasma antigen to determine the value of this test in the diagnosis of coccidioidomycosis. Many of the patients were immunosuppressed and critically ill. RESULTS: The Histoplasma antigen test had positive results when urine samples from 11 (58%) of 19 patients who had acute or chronic coccidioidomycosis were tested. The sensitivity was highest for patients who had acute coccidioidomycosis, and antigenuria was detected in 11 (79%) of 14 patients. One patient who had chronic coccidioidomycosis but who had a negative result when a urine sample was tested had antigen detected in bronchoalveolar lavage fluid. CONCLUSIONS: Physicians should be alerted that infections with Coccidioides species may cause positive Histoplasma antigen test results. There is potential for the use of this test in the diagnosis of coccidioidomycosis by taking advantage of this observed cross-reactivity. The greatest benefit appears to be in the population of seriously ill patients with acute pneumonia who live in areas that are endemic for Coccidioides infection. PMID- 17278050 TI - Severe photosensitivity causing multifocal squamous cell carcinomas secondary to prolonged voriconazole therapy. AB - A 32-year-old woman was treated with long-term voriconazole therapy for recurrent aspergillosis associated with chronic granulomatous disease. A short time after commencement of voriconazole therapy, a severe photosensitivity reaction developed. Continued voriconazole exposure led to the development of multifocal facial squamous cell carcinomas. The photosensitivity reaction resolved after the patient changed therapy to posaconazole. PMID- 17278051 TI - Revaccination with measles, tetanus, poliovirus, Haemophilus influenzae type B, meningococcus C, and pneumococcus vaccines in children after hematopoietic stem cell transplantation. AB - BACKGROUND: There is a decrease in antibody levels after hematopoietic stem cell transplant (HSCT), and such patients may be at increased risk of acquiring vaccine-preventable infection. A simple and validated revaccination schedule is required. The aim of this study was to evaluate the immunogenicity of a revaccination schedule for pediatric HSCT recipients. METHODS: Thirty-eight children (age, 1-18 years) who had undergone autologous or allogeneic HSCT for malignant diseases were recruited. All children received vaccinations in accordance with a predefined schedule. Antibody concentrations were measured before and 2-4 weeks after vaccination against tetanus; Haemophilus influenzae type b (Hib); meningococcus C; measles; poliovirus serotypes 1, 2, and 3; and 9 pneumococcus serotypes. RESULTS: Before vaccination, protective antibody levels were found for tetanus in 95% of patients (geometric mean concentration [GMC], 0.07 IU/mL; 95% CI, 0.05-0.1 IU/mL), for Hib in 63% (GMC, 0.34 microg/mL; 95% CI, 0.21-0.57 microg/mL), for measles in 60% (GMC, 102 mIU/mL; 95% CI, 41-253 mIU/mL), for meningococcus C in 11% (geometric mean titer [GMT], 1:4; 95% CI, 1:2 1:8.4), for all 3 poliovirus serotypes in 29%, and for all 9 pneumococcal serotypes in 0%. Vaccination resulted in a significant increase (P < or = .05) in antibody levels to each vaccine antigen studied, with 100% of patients achieving protection against tetanus (GMC, 2.2 IU/mL; 95% CI, 1.8-2.7 IU/mL), 100% achieving protection against Hib (GMC, 8.4 microg/mL; 95% CI, 7.6-9.3 microg/mL), 100% achieving protection against measles (GMC, 2435 mIU/mL; 95% CI, 1724-3439 mIU/mL), 100% achieving protection against meningococcus C (GMT, 1:5706; 95% CI, 1:3510-1:9272), 92% achieving protection against the 3 poliovirus serotypes, and > or = 80% achieving protection against each of the heptavalent pneumococcal conjugate vaccine-associated serotypes. No factors relevant to age, underlying disease, or treatment type were found to significantly influence responses. CONCLUSION: Revaccination of pediatric HSCT recipients in accordance with this revaccination schedule provides a high level of protection against these vaccine preventable diseases. PMID- 17278053 TI - Reimmunization after therapy for childhood cancer. PMID- 17278052 TI - Revaccination of children after completion of standard chemotherapy for acute leukemia. AB - BACKGROUND: After the treatment of patients with acute leukemia, there is a decrease in vaccine-specific antibody and an increased susceptibility to certain vaccine-preventable diseases. A simple revaccination schedule is warranted. METHOD: Fifty-nine children (age, 1-18 years) who had completed standard chemotherapy in accordance with Medical Research Council of United Kingdom protocols were recruited. All children received a single dose of Haemophilus influenzae type b (Hib), tetanus, diphtheria, acellular pertussis, meningococcus C, polio, measles, mumps, and rubella vaccines > or = 6 months after completion of treatment. Antibody concentrations were measured before vaccination and 2-4 weeks and 12 months after vaccination. RESULTS: Prevaccination antibody levels were protective for all patients for tetanus (geometric mean concentration [GMC], 0.13 IU/mL; 95% CI, 0.1-0.17 IU/mL), for 87% for Hib (GMC, 0.5 microg/mL; 95% CI, 0.37-0.74 microg/mL), for 71% for measles (GMC, 301 mIU/mL; 95% CI, 163-557 mIU/mL), for 12% for meningococcus C (geometric mean titer [GMT], 1:2.9; 95% CI, 1:2.2 to 1:3.9), and for 11% for all 3 poliovirus serotypes. Revaccination resulted in a significant increase in levels of antibody to each vaccine antigen, with 100% of patients achieving optimal antitetanus antibody concentrations (defined as > 0.1 IU/mL; 1.5 IU/mL; 95% CI, 1.1-2.1 IU/mL), 93% achieving optimal antibody concentrations to Hib (defined as > 1.0 microg/mL; 6.5 microg/mL; 95% CI, 5.1-8.2 microg/mL), 94% achieving optimal antibody concentrations to measles (defined as > or = 120 mIU/mL; 2720 mIU/mL; 95% CI, 1423-5198 mIU/mL), 96% achieving optimal antibody concentrations to meningococcus C (defined as > or = 1:8; 1:1000; 95% CI, 1:483-1:2064), and 85% achieving optimal antibody concentrations to all the 3 poliovirus serotypes (defined as > or = 1:8). For the majority of subjects, protection persisted for at least 12 months after vaccination. CONCLUSION: Revaccination of children after standard chemotherapy is important, and protection can be achieved in the majority of these children using a simple schedule of 1 vaccine dose at 6 months after completion of leukemia therapy. PMID- 17278054 TI - Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study. AB - BACKGROUND: Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear. METHODS: We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates. RESULTS: Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 [15%] of 168 vs. 30 [28%] of 109; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 [7%] of 168 vs. 29 [27%] of 109; OR, 0.21; 95% CI, 0.10-0.46; P<.0001); children with HEV-71 genogroup B5 were more likely to be part of a family cluster (OR, 6.26; 95% CI, 2.77-14.18; P<.0001). Children with HEV-71 and coinfected with another enterovirus or adenovirus were no more likely to have CNS disease. CONCLUSIONS: Genogroups of HEV-71 may differ with regard to the risk of causing CNS disease and the association with family clusters. Dual infections are common, and all possible causes should be excluded before accepting that the first virus identified is the causal agent. PMID- 17278055 TI - Meningococcal meningitis: unprecedented incidence of serogroup X-related cases in 2006 in Niger. AB - BACKGROUND: In Niger, epidemic meningococcal meningitis is primarily caused by Neisseria meningitidis (Nm) serogroup A. However, since 2002, Nm serogroup W135 has been considered to be a major threat that has not yet been realized, and an unprecedented incidence of Nm serogroup X (NmX) meningitis was observed in 2006. METHODS: Meningitis surveillance in Niger is performed on the basis of reporting of clinically suspected cases. Cerebrospinal fluid specimens are sent to the reference laboratory in Niamey, Niger. Culture, latex agglutination, and polymerase chain reaction are used whenever appropriate. Since 2004, after the addition of a polymerase chain reaction-based nonculture assay that was developed to genogroup isolates of NmX, polymerase chain reaction testing allows for the identification of Nm serogroup A, Nm serogroup B, Nm serogroup C, NmX, Nm serogroup Y, and Nm serogroup W135. RESULTS: From January to June 2006, a total of 4185 cases of meningitis were reported, and 2905 cerebrospinal fluid specimens were laboratory tested. NmX meningitis represented 51% of 1139 confirmed cases of meningococcal meningitis, but in southwestern Niger, it represented 90%. In the agglomeration of Niamey, the reported cumulative incidence of meningitis was 73 cases per 100,000 population and the cumulative incidence of confirmed NmX meningitis was 27.5 cases per 100,000 population (74.6 cases per 100,000 population in children aged 5-9 years). NmX isolates had the same phenotype (X : NT : P1.5), and all belonged to the same sequence type (ST-181) as the NmX isolates that were circulating in Niamey in the 1990s. Nm serogroup W135 represented only 2.1% of identified meningococci. CONCLUSIONS: This is, to our knowledge, the first report of such a high incidence of NmX meningitis, although an unusually high incidence of NmX meningitis was also observed in the 1990s in Niamey. The increasing incidence of NmX meningitis is worrisome, because no vaccine has been developed against this serogroup. Countries in the African meningitis belt must prepare to face this potential new challenge. PMID- 17278056 TI - Measurement of adult antibacterial drug use in 130 US hospitals: comparison of defined daily dose and days of therapy. AB - BACKGROUND: Hospitals are advised to measure antibiotic use and monitor its relationship to resistance. The World Health Organization's recommended metric is the defined daily dose (DDD). An alternative measure is the number of days of therapy (DOT). The purpose of this study was to contrast these measures. METHODS: We measured the use of 50 antibacterial drugs that were administered to adults who were discharged from 130 US hospitals during 1 August 2002-31 July 2003. RESULTS: Of 1,795,504 patients, 1,074,174 received at least 1 dose of an antibacterial drug (59.8%). The mean (+/- standard deviation) of total antibacterial drug use measured by the number of DDDs per 1000 patient-days and the number of DOTs per 1000 patient-days were not significantly different (792+/ 147 and 776+/-120, respectively; P=.137), although the correlation was poor (r=0.603). For some individual drugs, such as levofloxacin and linezolid, there was no significant difference between DDDs per 1000 patient-days and DOTs per 1000 patient-days, because the administered daily dosage was nearly equivalent to the DDD. When the administered dosage exceeded the DDD, such as for ampicillin sulbactam and cefepime, estimates of use based on DDDs per 1000 patient-days significantly exceeded those based on DOTs per 1000 patient-days (P<.001). When the administered dosage was less than the DDD, such as for piperacillin tazobactam and ceftriaxone, estimates of use based on DDDs per 1000 patient-days were significantly lower than those based on DOTs per 1000 patient-days (P<.001). CONCLUSION: The measurement of aggregate hospital antibiotic use by DDDs per 1000 patient-days and DOTs per 1000 patient-days is discordant for many frequently used antibacterial drugs, because the administered dose is dissimilar from the DDD recommended by the World Health Organization. DDD methods are useful for benchmarking purposes but cannot be used to make inferences about the number of DOTs or relative use for many antibacterial drugs. PMID- 17278057 TI - Measuring antimicrobial use: the way forward. PMID- 17278058 TI - Clinical evaluation of the microscopic-observation drug-susceptibility assay for detection of tuberculosis. AB - BACKGROUND: There is an urgent need for low-cost methods for rapid, accurate detection of Mycobacterium tuberculosis in clinical specimens. The microscopic observation drug-susceptibility (MODS) assay is a relatively low-cost and simple liquid culture method that has been proposed for use in resource-limited environments. METHODS: This prospective study evaluated the performance of the MODS assay for detection of M. tuberculosis in persons undergoing evaluation for pulmonary tuberculosis in Brazil and Honduras. Respiratory specimens were evaluated using smear microscopy, culture on Lowenstein-Jensen medium, and culture using the MODS assay. A subset of specimens was also cultured using the Mycobacterial Growth Indicator Tube (MGIT) 960 automated system (Becton Dickinson). A study subject was considered to have tuberculosis if at least 1 culture on Lowenstein-Jensen medium was positive for M. tuberculosis. FINDINGS: A total of 1639 respiratory specimens obtained from 854 study subjects were analyzed. On a per-subject basis, MODS sensitivity was 97.5% (95% confidence interval [CI], 95.7-98.6), and specificity was 94.4% (95% CI, 93.1-95.2). Median times to detection were 21 days (interquartile range [IQR], 17-25 days) and 7 days (IQR, 5-10) for culture on Lowenstein-Jensen medium and for the MODS assay, respectively (P<.01). For 64 specimens cultured using the MGIT 960 automated system, median time to growth was similar for the MODS assay (7 days; IQR, 7-10 days) and the MGIT 960 automated system (8 days; IQR, 6-11.5 days; P=.16). The percentage of contaminated cultures was lower for the MODS assay than for culture on Lowenstein-Jensen medium (3.8% vs. 5.8%; P<.01). CONCLUSIONS: The MODS assay is a relatively simple test whose good performance characteristics for detection of pulmonary tuberculosis may make it suitable for resource-limited environments. PMID- 17278059 TI - Mutant selection window hypothesis updated. AB - The mutant selection window hypothesis postulates that, for each antimicrobial pathogen combination, an antimicrobial concentration range exists in which selective amplification of single-step, drug-resistant mutants occurs. This hypothesis suggests an antimutant dosing strategy that is keyed to the upper boundary of the selection window: the mutant prevention concentration. Correlations are described between the mutant prevention concentration--a static parameter that is measured with agar plates--and fluctuating drug concentrations that restrict mutant amplification in vitro and in animals. When drug resistance is acquired stepwise, the mutant selection window increases, making the suppression of each successive mutant increasingly more difficult. For agents that kill drug-resistant mutants in a drug concentration-dependent manner, the use of the area under the 24-h time-drug concentration curve value divided by the value of the mutant prevention concentration is suggested as an index for designing antimutant dosing regimens. The need for such regimens is emphasized by a clinical example in which acquisition of drug resistance occurs concurrently with eradication of susceptible bacterial cells. These data support using the mutant selection window to optimize antimicrobial dosing regimens. PMID- 17278060 TI - Human T lymphotropic virus type 1 (HTLV-1) proviral load in asymptomatic carriers, HTLV-1-associated myelopathy/tropical spastic paraparesis, and other neurological abnormalities associated with HTLV-1 infection. AB - Recent reports have demonstrated that human T lymphotropic virus type 1 (HTLV-1) is associated with other neurological abnormalities in addition to HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been well established that high HTLV-1 proviral loads are associated with the development of HAM/TSP. We now demonstrate, for the first time, to our knowledge, that HTLV-1 proviral loads in patients with other neurological abnormalities are also significantly higher than in asymptomatic HTLV-1 carriers. PMID- 17278061 TI - Associations among Epstein-Barr virus subtypes, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder in bone marrow transplant recipients. AB - The association between Epstein-Barr virus subtype, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder was examined in a group of 25 bone marrow transplant recipients. A highly statistically significant correlation was observed between the human leukocyte antigen B51 allele and development of posttransplantation lymphoproliferative disorder (P=.0016). This study provides, to our knowledge, the first evidence that the human leukocyte antigen B51 allele might predispose bone marrow transplant recipients to Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder. PMID- 17278062 TI - A meta-analysis on the effects of antibiotic treatment on duration of symptoms caused by infection with Campylobacter species. AB - Eleven randomized, controlled trials of antibiotic treatment versus placebo in patients with Campylobacter species infection were pooled in a meta-analysis. Antibiotic treatment shortened the duration of intestinal symptoms by 1.32 days (95% confidence interval, 0.64-1.99; P<.0001). Because of problems with drug resistance, a restrictive attitude towards the administration of antibiotics in uncomplicated cases is advised. PMID- 17278063 TI - The health burden of Campylobacter infection and the impact of antimicrobial resistance: playing chicken. PMID- 17278064 TI - A febrile illness with generalized papular rash involving the palms and soles. PMID- 17278065 TI - Necrotizing soft-tissue infection: diagnosis and management. AB - Necrotizing soft-tissue infections (NSTIs) are highly lethal. They are frequent enough that general and specialty physicians will likely have to be involved with the management of at least 1 patient with NSTI during their practice, but they are infrequent enough that familiarity with the disease will seldom be achieved. Establishing the diagnosis of NSTI can be the main challenge in treating patients with NSTI, and knowledge of all available tools is key for early and accurate diagnosis. The laboratory risk indicator for necrotizing fasciitis score can be helpful for distinguishing between cases of cellulitis, which should respond to medical management alone, and NSTI, which requires operative debridement in addition to antimicrobial therapy. Imaging studies are less helpful. The mainstay of treatment is early and complete surgical debridement, combined with antimicrobial therapy, close monitoring, and physiologic support. Novel therapeutic strategies, including hyperbaric oxygen and intravenous immunoglobulin, have been described, but their effect is controversial. Identification of patients at high risk of mortality is essential for selection of patients that may benefit from future novel treatments and for development and comparison of future trials. PMID- 17278066 TI - Emerging viruses: coming in on a wrinkled wing and a prayer. AB - The role that bats have played in the emergence of several new infectious diseases has been under review. Bats have been identified as the reservoir hosts of newly emergent viruses such as Nipah virus, Hendra virus, and severe acute respiratory syndrome-like coronaviruses. This article expands on recent findings about bats and viruses and their relevance to human infections. It briefly reviews the history of chiropteran viruses and discusses their emergence in the context of geography, phylogeny, and ecology. The public health and trade impacts of several outbreaks are also discussed. Finally, we attempt to predict where, when, and why we may see the emergence of new chiropteran viruses. PMID- 17278067 TI - Activities, achievements, and lessons learned during the first 10 years of the Foodborne Diseases Active Surveillance Network: 1996-2005. AB - Since the establishment of the Foodborne Diseases Active Surveillance Network (FoodNet) in 1996, it has been an essential resource for the surveillance and investigation of foodborne disease in the United States. FoodNet has had a major impact on food safety because it conducts population-based, active surveillance for laboratory-confirmed infections from 9 pathogens commonly transmitted through food. Each year, FoodNet publishes the National Report Card on Food Safety, which is used by regulatory agencies, industry and consumer groups, and public health personnel to prioritize and evaluate food safety interventions and monitor progress toward national health objectives. FoodNet also determines the human health impact of foodborne illness by conducting related epidemiological studies that contribute to the estimates of the overall burden of foodborne illness, attribute the burden of foodborne illness to specific foods and settings, and address important foodborne disease-related issues, such as antimicrobial resistance and sequelae from foodborne infections. This article summarizes the activities, achievements, and lessons learned during the first 10 years of FoodNet. PMID- 17278068 TI - Metabolic syndrome in HIV-infected patients from an urban, midwestern US outpatient population. AB - BACKGROUND: The association between the use of highly active antiretroviral therapy (HAART) and an increased risk of metabolic syndrome and cardiovascular disease remains unclear. METHODS: We conducted a prospective, cross-sectional study of the risk factors associated with metabolic syndrome and cardiovascular disease among patients from an urban outpatient human immunodeficiency virus (HIV) clinic. Evaluation included laboratory data that were obtained after an overnight fast and a health survey that assessed traditional risk factors associated with cardiovascular disease, HIV-related factors, and comorbidities. Data collected were compared with data files from a cohort from the National Health and Nutrition Examination Survey (NHANES; 2001-2002) of persons who were seronegative for HIV infection who were matched for age, sex, race, and tobacco use. RESULTS: Four hundred seventy-one HIV-infected subjects provided complete data. The overall prevalence of metabolic syndrome was similar between the group HIV-infected patients and the group of persons who were seronegative for HIV infection (25.5% vs. 26.5%, respectively), although the HIV-infected patients had a significantly smaller waist circumference, lower body mass index, lower high density lipoprotein cholesterol levels, higher triglyceride levels, and lower glucose levels, compared with the subjects from the NHANES cohort. Framingham 10 year risk scores were also similar between the 2 groups. HIV-infected patients with metabolic syndrome were more likely to be diabetic, older, and white and have a high CD4 cell count and body mass index, compared with patients without metabolic syndrome (P<.05 for all). The type or duration of antiretroviral therapy was not an independent risk factor for metabolic syndrome. CONCLUSIONS: The prevalence of metabolic syndrome is high among HIV-infected persons, but not higher than the prevalence among HIV-uninfected persons. Traditional risk factors play a more significant role in the development of metabolic syndrome than do HIV treatment-associated factors. PMID- 17278069 TI - Metabolic syndrome in HIV-infected patients: no different than the general population? PMID- 17278070 TI - The incidence and natural history of osteonecrosis in HIV-infected adults. AB - BACKGROUND: Osteonecrosis is increasingly recognized as a debilitating complication of human immunodeficiency virus (HIV) infection, but the natural history has not been well described. We previously documented a high prevalence (4.4%) of magnetic resonance imaging (MRI)-documented osteonecrosis of the hip in a cohort of 339 asymptomatic HIV-infected patients. The present study was designed to determine the incidence of newly diagnosed osteonecrosis in this cohort and to describe the natural history of osteonecrosis in HIV-infected patients. METHODS: Asymptomatic HIV-infected patients with a previous hip MRI negative for osteonecrosis underwent follow-up MRI. Patients with asymptomatic or symptomatic osteonecrosis were enrolled in a natural history study, which included serial MRIs and a physiotherapy follow-up. RESULTS: Two hundred thirty nine patients underwent a second MRI a median of 23 months after the initial MRI. Osteonecrosis of the femoral head was diagnosed in 3 patients (incidence, 0.65 cases per 100 person-years). During the period of January 1999 through April 2006, symptomatic hip osteonecrosis developed in 13 clinic patients (incidence, 0.26 cases per 100 person-years). Among 22 patients enrolled with symptomatic hip osteonecrosis, 18 had bilateral involvement of the femoral heads, and 7 had osteonecrosis involving other bones. Two (11%) of 18 asymptomatic patients and 13 (59%) of 22 symptomatic patients underwent total hip replacement. The percentage of involvement of the weight-bearing surface of the femoral head and the rate of progression to total hip replacement was significantly greater (P<.001) in symptomatic patients than in asymptomatic patients. CONCLUSIONS: HIV-infected patients are at approximately 100-fold greater risk of developing osteonecrosis than the general population. Disease progression is slower in asymptomatic patients than in symptomatic patients. Given the high frequency of total hip replacement in symptomatic patients, studies to assess preventive and treatment strategies are essential. PMID- 17278071 TI - Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment. AB - BACKGROUND: We evaluated the immunologic impact of highly active antiretroviral therapy in subjects who maintained human immunodeficiency virus type 1 (HIV-1) suppression through 6 years of receiving a lopinavir-ritonavir-based regimen. METHODS: A total of 100 antiretroviral-naive subjects with any CD4+ T cell count initiated therapy with lopinavir-ritonavir, stavudine, and lamivudine. Sixty three subjects who remained in the study for 6 years were assessed. Laboratory measurements included plasma HIV-1 RNA levels, multiparameter flow cytometry of immune cells, and markers of maturation and activation. RESULTS: After 6 years, 62 of 63 subjects had plasma HIV-1 RNA levels <50 copies/mL. The mean increase in CD4+ T cell count was 528 cells/microL (P<.001), and 81% of subjects had CD4+ T cell counts >500 cells/microL, compared with 21% of subjects at baseline. The mean ratio of CD4+ T cell count to CD8+ T cell count increased from 0.38 at baseline to 0.96 at year 6 (P<.001). The percentage of subjects with cell counts below the lower limit of normal at year 6, compared with at baseline, was significantly decreased for total T cells, B cells, and natural killer cells. At year 6, the median CD4+ T cell activation level was 3.4%, and the median CD8+ T cell activation level was 5.8%. CONCLUSIONS: The receipt of a lopinavir-ritonavir based regimen resulted in ongoing immune reconstitution through 6 years of therapy in a cohort of HIV-1-infected, antiretroviral-naive subjects with suppressed HIV-1 RNA levels. Normalization of activation marker expression on CD4+ and CD8+ T cell subsets was demonstrated. PMID- 17278073 TI - When a paradoxical increase in serum galactomannan antigen during caspofungin therapy is not paradoxical after all. PMID- 17278075 TI - Illness in travelers visiting friends and relatives: what can be concluded? PMID- 17278078 TI - Group A streptococcal pharyngitis and penicillin G. PMID- 17278080 TI - Community-acquired Listeria monocytogenes meningitis in adults. PMID- 17278079 TI - IMP-4-producing Pseudomonas aeruginosa in a French patient repatriated from Malaysia: impact of early detection and control measures. PMID- 17278082 TI - High colonization pressure might compromise the efficiency of routine methicillin resistant Staphylococcus aureus screening. PMID- 17278083 TI - Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. PMID- 17278084 TI - The influence of parental origin of X chromosome genes on the stature of patients with 45 X Turner syndrome. AB - Thirty-seven 45 X Turner syndrome patients with confirmed peripheral blood lymphocyte karyotype were initially selected to determine the origin of the retained X chromosome and to correlate it with their parents' stature. Blood samples were available in 25 families. The parental origin of the X chromosome was determined in 24 informative families through the analysis of the exon 1-CAG repeat variation of the androgen receptor gene. In 70.8% of the cases, the retained X chromosome was maternal in origin and 29.2% was paternal. When we classified the patients according to maternal (Xm) or paternal (Xp) X chromosome, there was a positive correlation between patients' and maternal heights only in the Xm group. There was no correlation with paternal height in either group, and a significant correlation with target height was only observed in the Xm group. In conclusion, maternal height is the best variable correlating with the height of 45 X Turner syndrome patients who retain the maternal X chromosome, suggesting a strong influence of genes located on the maternal X chromosome on stature. PMID- 17278085 TI - Mitochondrial genome differences between the stingless bees Melipona rufiventris and Melipona mondury (Apidae: Meliponini). AB - Within the Meliponini, a widely distributed group of stingless bees, Melipona rufiventris has been considered as a single, cohesive species. Recently, analysis of morphological characters led to the splitting of this species into two species, M. mondury and M. rufiventris. The former occurs in the Atlantic Rain Forest ranging from Santa Catarina to Bahia States, while the latter is found in other parts of Brazil. We used PCR + RFLP to identify genetic marker patterns of the mtDNA between these species. Nine mtDNA regions were amplified and digested with four restriction enzymes (EcoRI, EcoRV, HindIII, and HinfI). Six species specific restriction sites were identified for M. mondury and M. rufiventris with all enzymes, except for HindIII. The molecular data agree with the morphological classification. PMID- 17278086 TI - Cloning, sequencing, expression, and antigenic characterization of rMSP4 from Anaplasma marginale isolated from Parana State, Brazil. AB - Anaplasmosis is a bovine intraerythrocytic disease caused by the bacterium Anaplasma marginale; it causes significant economic losses in tropical and subtropical regions, worldwide. The msp4 gene of an A. marginale strain isolated in Paran , Brazil, was amplified by PCR and sequenced; its cloning into the pET102/D-TOPO vector produced an msp4-6xHis-V5-HP thioredoxin fusion gene construct. This recombinant clone was over-expressed in Escherichia coli BL21(DE 3); the expressed fusion protein was found almost entirely in the insoluble form (inclusion bodies) in the cell lysate. The inclusion bodies were solubilized with urea and the recombinant protein was purified by Ni-NTA column and dialyzed. This method produced a relatively high yield of rMSP4, which was used to immunize rabbits. The deduced amino acid sequence encoded by MSP4 showed 99% homology to A. marginale isolates from Florida, USA, and from Minas Gerais, Brazil. Both rMSP4 and native MSP4 were recognized by post-immunization rabbit serum, showing that rMSP4 has conserved epitopes. As antigenicity was preserved, rMSP4 might be useful for the development of vaccine against anaplasmosis. PMID- 17278087 TI - Kinetics of PME/Pi in pig kidneys during cold ischemia. AB - Quality assessment of renal grafts via (31)P magnetic resonance spectroscopy (MRS) has been investigated since 1986. As ATP concentrations decay rapidly during cold ischemia, the ratio of phosphomonoesters (PME) to inorganic phosphate (Pi(O)) within the organ (PME/Pi(O)) is commonly used as a quality marker and is considered to be the most reliable parameter. MRS did not lead to any delay in the transplantation procedure since it was performed during the time necessary for immunological matching (cross-match). Differences in the time period until transplantation call for extrapolation of the measured ratio to the end of cold ischemia before correlating with graft performance after transplantation. Therefore, quantitative determination of PME/Pi(O) kinetics is essential. As a model for metabolite decay in human renal grafts, pig kidneys obtained from a slaughterhouse were monitored for up to 80 h via (31)P MRS at 2 T. By employing chemical shift imaging (CSI) with a spatial resolution of approximately 1 x 1 x 4 cm(3), it was possible to reduce partial volume effects significantly. The improved spectral resolution gained through CSI enabled reliable PME/Pi(O) ratios to be determined only from those voxels containing renal tissue. Spectra were fitted automatically using the magnetic resonance user interface (MRUI), with prior knowledge obtained from unlocalized spectra when necessary. A monoexponential time dependence of PME/Pi(O) for histidine-tryptophane-alpha ketoglutarate (HTK)-perfused kidneys during cold ischemia was observed, and the determined value of the decay constant alpha was 0.0099 +/- 0.0012 h(-1). In University of Wisconsin solution (UW)-perfused kidneys, an alpha of 0.0183 +/- 0.0053 h(-1) was determined. Determination of the decay constant enables a usable extrapolation of PME/Pi(O) for quality assessment of UW perfusion and a reliable extrapolation for HTK-perfused human renal grafts. PMID- 17278088 TI - Modeling dynamic cerebral blood volume changes during brain activation on the basis of the blood-nulled functional MRI signal. AB - Recently, vascular space occupancy (VASO) based functional magnetic resonance imaging (fMRI) was proposed to detect dynamic cerebral blood volume (CBV) changes using the blood-nulled non-selective inversion recovery (NSIR) sequence. However, directly mapping the dynamic CBV change by the NSIR signal change is based on the assumption of slow water exchange (SWE) around the capillary regime without cerebral blood flow (CBF) effects. In the present study, a fast water exchange (FWE) model incorporating with flow effects was derived from the Bloch equations and implemented for the quantification of dynamic CBV changes using VASO-fMRI during brain activation. Simulated results showed that only subtle differences in CBV changes estimated by these two models were observed on the basis of previously published VASO results. The influence of related physiological and biophysical factors within typical ranges was evaluated in steady-state simulations. It was revealed that in the transient state the CBV curves could be delayed in comparison with measured NSIR curves owing to the imbalance between the inflowing and outflowing blood signals. PMID- 17278089 TI - Breast tumours following combined hormone replacement therapy express favourable prognostic factors. AB - The aim of the present study was to evaluate the association between different types of hormone replacement therapy (HRT) and risk of specific breast cancer subgroups. A population-based prospective cohort study including 12,583 peri- or postmenopausal women were followed using record-linkage with national cancer registries. During an average follow-up of 4.5 years, 332 cases of invasive breast cancer were diagnosed. Tumour samples were available from 283 cases. These tumours were re-evaluated according to histological type, grade, and mitotic index. Evaluation of tumours included estrogen and progesterone receptor status (ERalpha, ERbeta and PgR), as well as expression of Ki67, HER2, cyclin D1 and p27. The incidence of breast cancer in current users of combined HRT (CHRT) was significantly higher than in non-users. The difference corresponded to an adjusted relative risk (95% confidence interval) of 3.01 (2.35-3.84) as obtained using a Cox's proportional hazards analysis. CHRT was associated with lobular tumours (3.48:1.99-6.10), grade 1 tumours (4.46:2.79-7.13) and tumours with a low mitotic index (4.35:2.99-6.34). CHRT was not related to any specific subgroup in terms of ERalpha-, ERbeta- or PgR-expression. CHRT was associated with low proliferating tumours, defined by the Ki67 index (3.58:2.60-4.93), HER2 amplified tumours (4.40:1.93-10.06), low expression of the oncogene cyclin D1 (3.14:2.32 4.23) and high expression of the tumour suppressor gene p27 (3.47:2.40-5.01). Use of estrogen-alone HRT (ERT) was not associated with any statistically significant risk of breast cancer. We conclude that the use of CHRT is associated with an increased incidence of breast tumours with comparatively favourable prognostic factors. PMID- 17278090 TI - A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland). AB - High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50 69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk. PMID- 17278091 TI - Smoking and survival after breast cancer diagnosis. AB - We examined whether a history of smoking is associated with an increased risk of death from any cause or from breast cancer, among women diagnosed with breast cancer. This was a prospective observational study among 5,056 women from the Nurses' Health Study with Stages I-III invasive breast cancer diagnosed between 1978 and 2002 and for whom we had information on smoking, and who were followed until January 2002 or death, whichever came first. Subjects were classified as current, former or never smokers based upon smoking status at the biennial questionnaire immediately preceding the breast cancer diagnosis. In multivariate adjusted analyses, compared with never smokers, women who were current smokers had a 43% increased adjusted relative risk (RR) [95% confidence interval (95% CI): 1.24-1.65] of death from any cause. A strong linear gradient was observed with the number of cigarettes per day smoked, p-trend <0.0001; the RR (95% CI) for 1-14, 15-24 and 25 or more cigarettes per day was 1.27 (1.01-1.61), 1.30 (1.08-1.57) and 1.79 (1.47-2.19). In contrast, there was no association with current smoking and breast cancer death; the RR (95% CI) was 1.00 (0.83-1.19). Current and past smokers were more likely than never smokers to die from primary lung cancer, chronic obstructive pulmonary disease and other lung diseases. We conclude that a history of smoking increased mortality following diagnosis with breast cancer, but did not increase mortality from breast cancer. PMID- 17278092 TI - Evidence for the role of aberrant DNA methylation in the pathogenesis of Lynch syndrome adenomas. AB - Colorectal cancer (CRC) forms through a series of histologic steps that are accompanied by mutations and epigenetic alterations, which is called the polyp cancer sequence. The role of epigenetic alterations, such as aberrant DNA methylation, in the polyp-cancer sequence in sporadic CRC and particularly in hereditary colon cancer is not well understood. Consequently, we assessed the methylation status of CDKN2A/p16, MGMT, MLH1 and p14(ARF) in adenomas arising in the Lynch syndrome, a familial colon cancer syndrome caused by MLH1 and MSH2 mutations, to determine if DNA methylation is a "second hit" mechanism in CRC and to characterize the role of DNA methylation in the polyp phase of the Lynch syndrome. We found MLH1 and p14(ARF) are methylated in 53 and 60% of the Lynch syndrome adenomas and in 4 and 20% of sporadic adenomas, whereas CDKN2A/p16 and MGMT are methylated in 6 and 14% of the Lynch syndrome adenomas versus 50 and 64% of sporadic adenomas. Therefore, the frequency and pattern of gene methylation varies between the Lynch syndrome and sporadic colon adenomas, implying differences in the molecular pathogenesis of the tumors. MLH1 methylation in the Lynch syndrome adenomas suggests gene methylation might have a role in the initiation of these neoplasms. PMID- 17278093 TI - Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patients. AB - NY-ESO-1 specific humoral responses are frequently observed in patients with various types of NY-ESO-1 antigen expressing tumors. In a large proportion of NY ESO-1 antibody-positive patients of NY-ESO-1-specific CD8 T-cells can also be detected suggesting that monitoring of the NY-ESO-1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY-ESO-1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY-ESO-1 protein formulated with cholesterol-bearing hydrophobized pullulan (CHP-NY-ESO-1) and investigated the humoral immune responses against NY-ESO-1. Seven patients were NY-ESO-1 antibody negative and 2 patients were positive prior to vaccination. Vaccination with CHP NY-ESO-1 resulted in the induction or increase of NY-ESO-1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY-ESO-1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY-ESO 1 antibody-positive cancer patients. A peptide spanning amino acids 91-108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero-positive patients, being the most dominant antigenic epitope in NY-ESO-1 for antibody recognition in cancer patients. In conclusion, we showed that CHP-NY-ESO 1 protein vaccination had a potent activity for inducing humoral immune responses against NY-ESO-1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY-ESO-1. PMID- 17278094 TI - The effects of combined antioxidant (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single-strand breaks and levels of insulin-like growth factor-1/IGF-binding protein 3 in the ferret model of lung cancer. AB - Insulin-like growth factor 1 (IGF-1) and its major binding protein, IGF binding protein 3 (IGFBP-3) are implicated in lung cancer and other malignancies. We have previously shown that the combination of three major antioxidants [beta-carotene (BC), alpha-tocopherol (AT) and ascorbic acid (AA)] can prevent lung carcinogenesis in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-treated and smoke-exposed (SM) ferret model, which is highly analogous to humans. The present study is aimed at determining the effect of the combination of BC, AT and AA on antioxidant capacity, lymphocyte DNA damage, plasma IGF-1 and IGFBP-3 concentrations, as well as on IGF-1/IGFBP-3 mRNA expression in the tissues (lung and liver) of the ferrets. Ferrets were treated with or without combined antioxidant (BC, AT and AA) supplementation (AOX) for 6 months in the following 4 groups: (i) control; (ii) SM+NNK; (iii) AOX; and (iv) SM+NNK+AOX. Combined AOX supplementation significantly attenuated SM+NNK induced lymphocyte DNA damage in the ferret, while increasing resistance to oxidative damage when challenged with H(2)O(2) in vitro. Ferrets treated with SM+NNK had significantly lower IGFBP-3 mRNA expression in lungs, whereas there was significantly higher IGFBP-3 mRNA expression in the liver, as well as higher circulating IGFBP-3 concentrations. Combined AOX supplementation did not affect the plasma or tissue (lung and liver) ratio of IGF-1/IGFBP-3. Combined antioxidant supplementation provides protection against smoke-induced oxidative DNA damage, but does not affect the IGF-1/IGFBP-3 system. Differential expression of IGFBP-3 in different tissues indicates that caution should be taken when using plasma IGFBP-3 as a biomarker of tissue status. PMID- 17278095 TI - Reproductive and hormonal factors and risk of lung cancer in women: a prospective cohort study. AB - Several lines of evidence suggest that endocrine factors may play a role in the development of lung cancer, but the evidence is limited and inconsistent. We investigated the association of reproductive and hormonal factors with risk of lung cancer in the National Breast Screening Study, which included 89,835 Canadian women aged 40-59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases provided data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between hormonal factors and lung cancer. During a mean of 16.4 years of follow-up, we observed 750 incident lung cancer cases. After adjustment for covariates, parous women were not at increased risk of lung cancer (HR = 1.18, 95% CI 0.94-1.47) relative to nulliparous women; however, there was a modest increase in risk with increasing parity, reaching a HR of 1.42, 95% CI 1.06-1.88 in women who had 5 or more live births (p for trend 0.02). Among parous women, age at first live birth was inversely associated with risk. Women who had their first live birth at age 30 or older were at reduced risk relative to women who had their first live birth below age 23 (HR 0.68, 95% CI 0.50-0.93, p for trend 0.004). These associations did not differ by age at enrollment (40-49 vs. 50-59 years old), but were somewhat strengthened when attention was restricted to never smokers. Ever use of exogenous hormones showed little association with lung cancer risk; however, long term users of hormone replacement therapy were at slightly increased risk. Our results add to the limited existing evidence that certain reproductive and hormonal factors may be associated with lung cancer risk in women. PMID- 17278097 TI - Insulin resistance is inversely related to prostate cancer: a prospective study in Northern Sweden. AB - Factors related to insulin resistance have been implicated in prostate cancer development, however, few analytical studies support such an association. We performed a case control study on 392 prostate cancer cases and 392 matched controls nested in a prospective cohort in Northern Sweden. Plasma concentrations of C-peptide, leptin, glycated haemoglobin (HbA1c) and fasting and post-load glucose were analysed and homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Conditional logistic regression analyses were used to calculate odds ratios (OR) of prostate cancer. High levels of C-peptide, HOMA-IR, leptin and HbA1c were associated with significant decreases in risk of prostate cancer, with ORs for top vs. bottom quartile for C-peptide of 0.59 (95% Confidence Interval [CI], 0.40-0.89; p(trend) = 0.008), HOMA-IR 0.60 (95% CI, 0.38-0.94; p(trend) = 0.03), leptin 0.55 (95% CI, 0.36-0.84; p(trend) = 0.006) and HbA1c 0.56 (95% CI, 0.35-0.91; p(trend) = 0.02). All studied factors were strongly inversely related to risk among men less than 59 years of age at blood sampling, but not among older men, with a significant heterogeneity between the groups for leptin (p(heterogeneity) = 0.006) and fasting glucose (p(heterogeneity) = 0.03). C-peptide and HOMA-IR were strongly inversely related to non-aggressive cancer but were non-significantly positively related to risk of aggressive disease (p(heterogeneity) = 0.007 and 0.01, respectively). Our data suggest that androgens, which are inversely associated with insulin resistance, are important in the early prostate cancer development, whereas insulin resistance related factors may be important for tumour progression. PMID- 17278096 TI - Analysis of molecular pathways in sporadic neuroendocrine tumors of the gastro entero-pancreatic system. AB - Little is known about the molecular pathogenesis of neuroendocrine tumors (NET) of the gastro-entero-pancreatic (GEP) system. We analyzed genetic and epigenetic alterations as well as the CpG island methylator phenotype (CIMP). The study comprised 118 well-differentiated fore- and mid-gut GEP-NET from 71 patients. In addition to loss of heterozygosity (LOH), microsatellite instability (MSI) and the methylation status of various tumor associated genes were examined. The expression profile of p16, APC and MENIN was investigated by immunohistochemistry. None of the tumors was highly microsatellite unstable, LOH was found in 22.2%. Significant differences in promoter hypermethylation were identified in the RUNX3 and the O(6)-MGMT genes. We found a significant loss of p16 expression in insulinomas (p = 0.05) and functional NET (p = 0.01), respectively. APC was expressed less in gastrinomas (p = 0.01) and functional GEP NET (p = 0.05) vs. nonfunctional tumors. MENIN expression was reduced in pancreatic vs. extrapancreatic NET (p = 0.008) and in insulinomas vs. nonfunctional GEP-NET (p = 0.019) and NET associated with the carcinoid syndrome (p = 0.029). Further CIMP and a Ki-67 index >10% showed a close correlation. Outcome analysis of 19 patients showed a better survival for CIMP-negative patients. The analyses identified significant genetic and epigenetic alterations in well-differentiated fore- and mid-gut NET. CIMP, similar to Ki-67, might turn out to be of prognostic relevance. PMID- 17278098 TI - BRCA1-IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR. AB - Cyclin D1 plays an important role in cell cycle progression. In breast cancer, Cyclin D1 expression is deregulated by several mechanisms. We previously showed that in breast cancer cells, overexpression of BRCA1-IRIS induces Cyclin D1 overexpression and increases cell proliferation. BRCA1-IRIS alone or in complex with steroid receptor co-activators was targeted to the cyclin D1 promoter pre bound by the c-Jun/AP1 and activated its transcription, which could explain the co-overexpression of BRCA1-IRIS and Cyclin D1 in breast cancer cells coupled with their increased proliferation. We report here an alternate or a complementary pathway by which BRCA1-IRIS activates Cyclin D1 expression. BRCA1-IRIS overexpression decreases the expression of the dual specificity phosphatase, DUSP3/VHR, an endogenous inhibitor of several MAPKs, including c-Jun N-terminal kinase. Although, the mechanism by which BRCA1-IRIS overexpression accomplishes that is not yet known, it is sufficient to induce Cyclin D1 overexpression in a human mammary epithelial cell model. Cyclin D1 overexpression could be blocked by co-overexpression of VHR in those cells. Furthermore, in 2 breast cancer cell lines that overexpress both BRCA1-IRIS and Cyclin D1 (MCF-7 and SKBR3) depletion of BRCA1-IRIS by RNA interference attenuated the expression of Cyclin D1 by elevating the expression level of VHR. These data demonstrate a critical role for BRCA1-IRIS in human breast cancer cell-cycle control and suggest that deregulated expression of BRCA1-IRIS is likely to reduce dependence on normal physiological growth stimuli, thereby providing a growth advantage to tumor cells and a potential mechanism of resistance to endocrine therapy. PMID- 17278099 TI - Increased expression of VEGF121/VEGF165-189 ratio results in a significant enhancement of human prostate tumor angiogenesis. AB - Vascular endothelial growth factor (VEGF) is a proangiogenic factor upregulated in many tumors. The alternative splicing of VEGF mRNA renders 3 major isoforms of 121, 165 and 189 amino-acids in humans (1 less amino-acid for each mouse VEGF isoform). We have designed isoform specific real time QRT-PCR assays to quantitate VEGF transcripts in mouse and human normal and malignant prostates. In the human normal prostate, VEGF(165) was the predominant isoform (62.8% +/- 5.2%), followed by VEGF(121) (22.5% +/- 6.3%) and VEGF(189) (p < 0.001) (14.6% +/ 2.1%). Prostate tumors showed a significant increase in the percentage of VEGF(121) and decreases in VEGF(165) (p < 0.01) and VEGF(189) (p < 0.05). However, the amount of total VEGF mRNA was similar between normal and malignant prostates. VEGF(164) was the transcript with the highest expression in the mouse normal prostate. Unlike human prostate cancer, tumors from TRAMP mice demonstrated a significant increase in total VEGF mRNA levels and in each of the VEGF isoforms, without changes in the relative isoform ratios. Morpholino phosphorodiamide antisense oligonucleotide technology was used to increase the relative amount of VEGF(121) while proportionally decreasing VEGF(165) and VEGF(189) levels in human prostate cell lines, through the modification of alternative splicing, without changing transcription levels and total amount of VEGF. The increase in the VEGF(121)/VEGF(165-189) ratio in PC3 cells resulted in a dramatic increase in prostate tumor angiogenesis in vivo. Our results underscore the importance of VEGF(121) in human prostate carcinoma and demonstrate that the relative expression of the different VEGF isoforms has an impact on prostate carcinogenesis. PMID- 17278101 TI - Biliary tract cancer and stones in relation to chronic liver conditions: A population-based study in Shanghai, China. AB - Biliary tract cancers are relatively rare but fatal tumors. Apart from a close link with gallstones and cholangitis, risk factors for biliary tract cancer are obscure. Chronic liver conditions, including liver cirrhosis, have been linked to a higher risk of biliary tract cancer. In a population-based case-control study conducted in Shanghai, China, we investigated the relationships of a history of chronic hepatitis and liver cirrhosis as well as a family history of liver cancer with biliary tract cancer risk. The study included 627 patients with biliary tract cancers (368 gallbladder, 191 bile duct and 68 ampulla of Vater), 1,037 patients with biliary stones (774 gallbladder stones and 263 bile duct stones) and 959 healthy subjects randomly selected from the population. Bile duct cancer was associated with self-reports of chronic liver conditions, including a history of chronic hepatitis (OR = 2.0, 95% CI 0.9-4.4), liver cirrhosis (OR = 4.7, 95% CI 1.9-11.7) and a family history of primary liver cancer (OR = 2.0, 95% CI 1.0 3.9). The excess risk persisted after adjustment for gallstones and were more pronounced among subjects without gallstones (OR = 5.0, 95% CI 1.3-20.0 and OR = 4.9, 95% 2.0-12.2, respectively). History of liver conditions was also associated with an excess of biliary stones (OR = 1.9, 95% CI 1.2-3.0). No association was found for cancers of the gallbladder and ampulla of Vater. A history of chronic hepatitis and cirrhosis may be risk factors for extraheptic bile duct cancer. Given that chronic infection with hepatitis B virus (HBV) is the most common cause of liver disease in China, serologic markers of HBV need to be measured in future studies to examine the link between HBV and bile duct cancer. PMID- 17278102 TI - TAP expression reduces IL-10 expressing tumor infiltrating lymphocytes and restores immunosurveillance against melanoma. AB - Many immune therapeutic strategies are under development for melanoma to treat metastatic disease and prevent disease reoccurrence. However, human melanoma cells are often deficient in antigen processing and this appears to play a role in their expansion and escape from immunosurveillance. For example, expression of the transporters associated with antigen processing (TAP1 and TAP2) is down regulated in the mouse melanoma cell line B16F10. This results in a lack of tumor associated antigen processing, low surface expression of MHC Class I molecules and low immunogenicity. We observe that restoration of TAP1 expression by transfection resurrects the processing and presentation of viral antigens, and the melanoma-associated antigen, TRP-2. Immunization with irradiated B16F10/rTAP1 transfected cells generates CTLs that are capable of killing B16F10/rTAP1 transfected targets and B16F10 targets deficient in TAP1. Furthermore, B16F10/rTAP1 transfectants grow at a significantly slower rate in mice than B16F10 cells. In an experimental model that closely recapitulates the clinical situation, treatment of B16F10 tumors in mice with a vaccinia virus vector expressing TAP1 also significantly decreases tumor growth in vivo. Furthermore, tumors treated with vaccinia TAP1 had significantly reduced numbers of immunosuppressive, CD3(+)/IL-10 positive, tumor infiltrating lymphocytes. Therefore, TAP1 expression restores both antigen presentation and immunogenicity in B16F10 melanoma cells and concomitantly reduces immunosuppressive IL-10 production at the local tumor site, thereby increasing immunosurveillance mechanisms against tumors. PMID- 17278100 TI - A modified version of galectin-9 suppresses cell growth and induces apoptosis of human T-cell leukemia virus type I-infected T-cell lines. AB - ATL is a fatal malignancy of T lymphocytes caused by HTLV-I infection and remains incurable. Galectins are a family of animal lectins that function both extracellularly (by interacting with cell surface and extracellular matrix glycoproteins and glycolipids) and intracellularly (by interacting with cytoplasmic and nuclear proteins) to modulate signaling pathways. We found that protease-resistant galectin-9 by modification of its linker peptide, hG9NC(null), prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells. The suppression of cell growth was inhibited by lactose, but not by sucrose, indicating that beta-galactoside binding is essential for hG9NC(null)-induced cell growth suppression. hG9NC(null) induced cell cycle arrest by reducing the expression of cyclin D1, cyclin D2, cyclin B1, Cdk1, Cdk4, Cdk6, Cdc25C and c Myc, and apoptosis by reducing the expression of XIAP, c-IAP2 and survivin. Most of these genes are regulated by NF-kappaB, which plays a critical role in oncogenesis by HTLV-I. hG9NC(null) suppressed IkappaBalpha phosphorylation, resulting in suppression of NF-kappaB. Most importantly, treatment with hG9NC(null) (6.7 mg/kg injected intraperitoneally every day) reduced tumor formation from an HTLV-I-infected T-cell line when these cells were inoculated subcutaneously into SCID mice. Our results suggest that hG9NC(null) could be a suitable agent for the management of ATL. PMID- 17278103 TI - CEBPbeta, JunD and c-Jun contribute to the transcriptional activation of the metastasis-associated C4.4A gene. AB - The glycosylphosphatidylinositol-anchored molecule C4.4A, which shares structural features with uPAR, is frequently expressed on carcinomas with upregulated expression during tumor progression. Moreover, rare expression on nontransformed epithelial cells is strongly increased during tissue remodeling, e.g., during wound healing. This strictly regulated expression prompted us to define transcriptional activation of the C4.4A gene. C4.4A transcription was analyzed in 2 syngenic rat tumor cell lines with low or high metastatic potential, respectively. Though genomic C4.4A DNA was present in both lines, C4.4A mRNA and transcription of a reporter construct containing the C4.4A promoter was only observed in the metastasizing subline. Deletions and point mutations in the C4.4A promoter-driven reporter construct revealed that activation of the TATA-less, GC rich core promoter (-1 to -50 bp) does not suffice to initiate transcription that requires coactivation of a proximal response element (-71 to -88 bp) and can be further increased by more distal response elements (-89 to -133 bp). Mobility shift and cotransfection studies showed that Sp3 binding enhances C4.4A transcription, whereas potential Sp1 binding sites were ineffective. C4.4A transcription essentially requires C/EBPbeta binding to a TRE/CCAAT composite element (-71 to -88 bp) as measured by ChIP assay. C4.4A transcription is strikingly enhanced by cotransfection with JunD or c-Jun, such that C4.4A is most strongly transcribed even in the C4.4A-negative tumor cell line after cotransfection with C/EBPbeta plus JunD or c-Jun. Thus, upregulation of C/EBPbeta during tumor progression and wound repair may well provide a sufficient trigger for transcription of the C4.4A gene. PMID- 17278104 TI - Imaging of Vx-2 rabbit tumors with alpha(nu)beta3-integrin-targeted 111In nanoparticles. AB - Earlier tumor detection can improve 5-year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. alpha(nu)beta(3) Targeted (111)In nanoparticles (NP) were developed and studied for detection of tumor angiogenesis. Studies were conducted in New Zealand white rabbits implanted 12 days earlier with Vx-2 tumor. alpha(nu)beta(3)-Targeted (111)In/NP bearing approximately 10 (111)In/NP vs. approximately 1 (111)In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand-targeting specificity. alpha(nu)beta(3)-Integrin-targeted NP with approximately 10 (111)In/NP provided better (p < 0.05) tumor-to-muscle ratio contrast (6.3 +/- 0.2) than approximately 1 (111)In/NP (5.1 +/- 0.1) or nontargeted particles with approximately 10 (111)In/NP (3.7 +/- 0.1) over the initial 2-hr postinjection. At 18 hr, mean tumor activity in rabbits receiving alpha(nu)beta(3)-integrin-targeted NP was 4 fold higher than the nontargeted control. Specificity of the NP for the tumor neovasculature was supported by in vivo competition studies and by fluorescence microscopy of alpha(nu)beta(3)-targeted fluorescent-labeled NP. Biodistribution studies revealed that the primary clearance organ in rabbits as a %ID/g tissue was the spleen. Circulatory half-life (t(1/2)beta) was estimated to be approximately 5 hr using a 2-compartment model. alpha(nu)beta(3)-Targeted (111)In perfluorocarbon NP may provide a clinically useful tool for sensitively detecting angiogenesis in nascent tumors, particularly in combination with secondary high resolution imaging modalities, such as MRI. PMID- 17278105 TI - Maternal smoking and the epidemic of testicular cancer--a nested case-control study. AB - For no apparent reason, the incidence of testicular cancer has increased to epidemic proportions in many countries. Pregnancy smoking has been suggested to be a cause. Previous analytical studies have been negative, but the inherent difficulties in retrospective assessment of this exposure have led to no definite conclusion. We have conducted a population-based case-control study on 192 cases of testicular germ-cell cancer-born in Sweden in 1973 onwards and aged >/=15 at cancer diagnosis-and 494 matched controls, where data on maternal smoking were collected during pregnancy. We found no association with testicular cancer for maternal smoking during pregnancy (OR, 0.91; 95% CI, 0.64-1.30), and there was no evidence of a dose-response effect. We conclude that the epidemic rise in testicular cancer in many populations is not due to the surge in smoking among women. PMID- 17278106 TI - Regulatory T-cell function of adult T-cell leukemia/lymphoma cells. AB - Adult T-cell leukemia/lymphoma (ATLL) patients are highly immunocompromised, but the underlying mechanism responsible for this state remains obscure. Recent studies demonstrated that FOXP3, which is a master control gene of naturally occurring regulatory T (Treg) cells, is expressed in the tumor cells from a subset of patients with ATLL. Since most ATLL cells express both CD4 and CD25, these tumors might originate from CD4(+)CD25(+)FOXP3(+) Treg cells, based on their phenotypic characteristics. However, whether ATLL cells actually function as Treg cells has not yet been clearly demonstrated. Here, we show that ATLL cells from a subset of patients are not only hypo-responsive to T-cell receptor mediated activation, but also suppress the proliferation of autologous CD4(+) non ATLL cells. Furthermore, ATLL cells from this subset of patients secrete only small amounts of IFN-gamma, and suppress IFN-gamma production by autologous CD4(+) non-ATLL cells. These are the first data showing that ATLL cells from a subset of patients function as Treg cells in an autologous setting. The present study provides novel insights into understanding the immunopathogenesis of ATLL, i.e., how HTLV-1-infected cells can survive in the face of host immune responses. It also adds to our understanding of ATLL patients' severely immunocompromised state. PMID- 17278107 TI - Identification of a novel single nucleotide polymorphism in the first tandem repeat sequence of the thymidylate synthase 2R allele. AB - Thymidylate synthase (TS) activity is an important determinant of response to chemotherapy with fluoropyrimidine prodrugs and its expression is largely determined by the number of functional upstream stimulatory factor (USF) E-box consensus elements present in the 5'regulatory region of the TYMS gene. Two known polymorphisms in this area, a variable number of tandem repeat (VNTR) consisting of 2 or 3 repeats (2R/3R) of a 28-bp sequence and a further G > C single nucleotide substitution within the second repeat of the 3R, result in genotypes with between 2 and 4 functional repeats in most humans. Here, we identify a further G > C SNP in the first repeat of the TYMS 2R allele, which effectively abolishes the only functional USF protein binding site in this promoter. The frequency of the new allele was found to be 4.2% (95% CI = 1.4-9.6%), accounting for 8.8% (95% CI = 2.9-19.3%) of all 2R alleles in our patient cohort. Thus, we observed that the lowest number of inherited functional binding sites is 1 instead of 2 as previously thought, and could potentially be 0 in a homozygous individual. This would severely decrease TS expression and may have implications for predicting efficacy and toxicity of therapy with commonly used fluorouracil based therapy regimes. PMID- 17278110 TI - Human papillomavirus-16 DNA methylation patterns support a causal association of the virus with oral squamous cell carcinomas. AB - Infection with human papillomavirus-16 (HPV-16) is the cause of most anogenital carcinomas. This virus is also detected in about 20% of all head and neck squamous cell carcinomas. While there is strong evidence for a causal etiological role in the case of tonsillar carcinomas, causal association with malignant lesions of the oral cavity is not yet conclusive. Our previous investigations of HPV-16 DNA methylation in anogenital sites have identified hypermethylation of the L1 gene and part of the long control region in many malignant lesions, but rarely in asymptomatic infections and low-grade precancerous lesions. Here, we report hypermethylation of this diagnostically important segment of the viral DNA in 10 out of 12 HPV-16 positive oral carcinomas from Mexican patients. These data indicate epigenetic changes of HPV-16 in oral carcinomas similar to those in anogenital carcinomas, suggesting carcinogenic processes under the influence of HPV-16 in most if not all of these oral malignant lesions. PMID- 17278108 TI - Soluble isoforms but not the transmembrane form of coxsackie-adenovirus receptor are of clinical relevance in epithelial ovarian cancer. AB - The coxsackie-adenovirus receptor (hCAR) has been extensively studied in context of adenoviral-based gene therapy for cancer. However, there is strong evidence that besides its decisive role in coxsackie and adenovirus cell-entry, hCAR is a component of epithelial tight junctions and involved in cell-cell adhesions in normal and cancer cells. Furthermore, this adhesion molecule behaves like a cell surface receptor endowed with tumor suppressive properties via signal transduction. Moreover, 3 truncated soluble isoforms of hCAR were recently identified. We investigated the quantitative expression of all known CAR isoforms in a training set of 140 ovarian cancer samples and 21 controls by RT-PCR. The expression levels of the various isoforms were compared with clinicopathologic parameters and their prognostic significance was assessed. Expression levels of all CAR isoforms were elevated in ovarian carcinomas as compared with those of non-malignant controls. mRNA-expression correlated with protein levels. Moreover, expression of the soluble isoforms CAR 3/7 and CAR 4/7 but not that of hCAR was significantly increased in advanced ovarian cancer as revealed by a highly significant correlation with FIGO stage and residual disease > 2 cm in diameter after debulking surgery. High expression of CAR 3/7 and 4/7 was shown to be of independent prognostic relevance for progression-free (CAR 4/7) and overall survival (CAR 3/7 and CAR 4/7). In conclusion, soluble CAR isoforms 3/7 and 4/7 may play a pivotal role in ovarian cancer biology, possibly by counteracting migration- and growth-inhibitory properties of the membranous hCAR and thus favoring cancer cell dissemination throughout the peritoneal cavity. PMID- 17278112 TI - Hemoglobin SE disease: a concise review. AB - An infant with Hb SE disease is reported. He was clinically well. Review of the literature shows that patients aged 18 and younger are usually well. On the other hand, more than half of those aged 20 and older developed sickling-related complications, including potentially life-threatening acute chest syndrome. These patients have 60-65% Hb S, similar to the percent Hb S in patients with Hb S/beta(+)-thalassemia. Their hematological features and clinical course appear to parallel those of Hb S/beta(+)-thalassemia. Patients have variable levels of anemia, and some develop clinical complications. With population migrations and increasing racial intermarriages, Hb SE disease is expected to be encountered more often around the globe. Patients with Hb SE disease should be followed and managed in a similar fashion as those with Hb S/beta(+)-thalassemia, and treated appropriately when they develop sickling-related symptoms and complications. PMID- 17278114 TI - Osteoporosis in young haemophiliacs from western India. AB - Arthropathies and joint deformities in patients with severe hemophilia result in prolonged immobilization, reduced physical activity, and predispose them for osteoporosis. This can lead to an increasing tendency of bone fragility and fractures in patients after trivial trauma. The aim of this study was to find out (i) the prevalence of osteoporosis in hemophilia patients and (ii) the association of osteoporosis with hemophilic arthropathy and related restricted physical activity. In this case-control study, 50 consecutive severe hemophilia patients aged between 20 and 50 years were evaluated for osteoporosis with measurement of bone mass density (BMD) by a DEXA scan and values were compared with that of 50 sex matched normal healthy controls. Major joints of the limbs were evaluated to determine the extent of joint damage and related disability. Forty-two patients had severe hemophilia A and 8 patients severe hemophilia B (efficient factor activity < 0.01 U/ml). BMD values (gms/cm(2)) of lumbar spine and left hip of the patients were significantly lower than that of controls (0.825 vs. 0.939; P < 0.0001 and 0.725 vs. 0.938; P < 0.0001, respectively). The incidence of osteoporosis (T score: -2.5 or more) was significantly higher in hemophiliacs. Incidence of fractures in adult life was also significantly higher in hemophiliacs compared to controls (12% vs. 0%). There was statistically significant correlation between joint evaluation scores and BMD of hip, but not with that of the lumbar spine. There was no correlation between Hepatitis-C virus status and BMD of any site. This shows that development of osteoporosis is a significant problem in patients with severe hemophilia in this country. Hence appropriate preventive measures such as early treatment and adequate mobilization, exercises, encouragement to participate in sporting activities, early assessment of bone density, and administration of anti-osteoporotic therapy is recommended. PMID- 17278115 TI - Identification of a unique epigenetic sub-microenvironment in prostate cancer. AB - The glutathione S-transferase P1 (GSTP1) gene promoter is methylated in tumour cells in more than 90% of prostate carcinomas. Recently, GSTP1 promoter methylation was identified in tumour-associated stromal cells in addition to the tumour epithelium. To define the extent and location of stromal methylation, epigenetic mapping using pyrosequencing quantification of GSTP1 promoter methylation and an anatomical three-dimensional reconstruction of an entire human prostate specimen with cancer were performed. Normal epithelium and stroma, tumour epithelium, and tumour-associated stromal cells were laser capture microdissected from multiple locations throughout the gland. As expected, the GSTP1 promoter in both normal epithelium and normal stromal cells distant from the tumour was not methylated and the tumour epithelium showed consistently high levels of promoter methylation throughout. However, tumour-associated stromal cells were found to be methylated only in a localized and distinct anatomical sub field of the tumour, revealing the presence of an epigenetically unique microenvironment within the cancer. Morphologically, the sub-field consisted of typical, non-reactive stroma, representing a genomic alteration in cells that appeared otherwise histologically normal. Similar epigenetic anatomical mapping of a control prostate gland without cancer showed low background methylation levels in all cell types throughout the specimen. These data suggest that stromal cell methylation can occur in a distinct sub-region of prostate cancer and may have implications for understanding tumour biology and clinical intervention. PMID- 17278116 TI - Formation of 8-nitroguanine and 8-oxoguanine due to reactions of peroxynitrite with guanine. AB - Reactions of peroxynitrite with guanine were investigated using density functional theory (B3LYP) employing 6-31G** and AUG-cc-pVDZ basis sets. Single point energy calculations were performed at the MP2/AUG-cc-pVDZ level. Genuineness of the calculated transition states (TS) was tested by visually examining the vibrational modes corresponding to the imaginary vibrational frequencies and applying the criterion that the TS properly connected the reactant and product complexes (PC). Genuineness of all the calculated TS was further ensured by intrinsic reaction coordinate (IRC) calculations. Effects of aqueous media were investigated by solvating all the species involved in the reactions using the polarizable continuum model (PCM). The calculations reveal that the most stable nitro-product complex involving the anion of 8-nitroguanine and a water molecule i.e. 8NO(2)G(-) + H(2)O can be formed according to one reaction mechanism while there are two possible reaction mechanisms for the formation of the oxo-product complex involving 8-oxoguanine and anion of the NO(2) group i.e. 8OG + NO(2)(-). The calculated relative stabilities of the PC, barrier energies of the reactions and the corresponding enthalpy changes suggest that formation of the complex 8OG + NO(2)(-) would be somewhat preferred over that of the complex 8NO(2)G(-) + H(2)O. The possible biological implications of this result are discussed. PMID- 17278118 TI - Sudden-onset blindness in sickle cell disease due to retinal artery occlusion. AB - Central retinal artery occlusion (CRAO) is a rare and potentially devastating cause of acute blindness in sickle cell disease (SCD) that is unique compared to classic sickle retinopathy. Few details related to this complication in SCD are known, including its risk factors, pathogenesis, presentation, treatment and outcomes. We present three patients with SCD and retinal artery occlusion. The overall variability in clinical presentation, treatment and prognosis reported in the literature underscores the need for a greater understanding of these factors as they relate to this complication in SCD. PMID- 17278117 TI - Fatal adenovirus hepatitis during maintenance therapy for childhood acute lymphoblastic leukemia. AB - Disseminated adenoviral infection with hepatitis is rare in children undergoing standard chemotherapy. We report on a 3(1/2)-year-old male with fatal adenovirus hepatitis receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Adenoviral hepatitis was proven by histology, viral culture, and PCR in a liver biopsy. Quantitative real-time PCR in the peripheral blood showed adenoviral DNA copy number >10(9)/ml. Despite aggressive supportive care and antiviral treatment with cidofovir, the patient died rapidly due to fulminant liver failure. Diagnostic and treatment options for adenovirus infection remain unsatisfactory for these patients. We propose suggestions for diagnosis and therapy. PMID- 17278119 TI - Prognostic significance of lymph node metastasis and surgical margin status for distal cholangiocarcinoma. AB - BACKGROUND AND OBJECTIVES: Prognostic indicators for patients with distal cholangiocarcinoma have not been confirmed because of its rarity. The aim of this study was to identify useful prognostic factors in patients undergoing surgical resection for distal cholangiocarcinoma. METHODS: Charts of 43 patients with distal cholangiocarcinoma who underwent surgical resection were retrospectively reviewed. Pancreatoduodenectomy was performed in 35 patients, and segmental bile duct resection in 8. Potential clinicopathological prognostic factors were examined by univariate and multivariate survival analysis. RESULTS: Postoperative complications occurred after surgery in 19 patients (44%), but there was no mortality. Overall survival rates were 72%, 53%, and 44% for 1, 3, and 5 years, respectively (median survival time, 26.0 months). Univariate analysis found that older age, pathological pancreatic invasion, lymph node metastasis, perineural invasion, positive surgical margin, and TNM stages II and III were significant predictors of poor prognosis (P < 0.05). Furthermore, lymph node metastasis and positive surgical margin were found to be significant independent predictors of poor prognosis with a Cox proportional hazards regression model (P < 0.05). CONCLUSIONS: These results suggest that lymph node metastasis and positive surgical margin as determined by surgical resection might be useful in predicting post-surgical outcome in patients with distal cholangiocarcinoma. PMID- 17278120 TI - A retrospective review of hearing in children with retinoblastoma treated with carboplatin-based chemotherapy. AB - BACKGROUND: Retinoblastoma occurs in approximately 4 per million children per year in the United States, usually before 2 years of age. In developed countries, 95% of children with tumor in one eye can be cured with enucleation, while children with tumor in both eyes require individualized therapy to preserve vision. Although enucleation and radiation are very effective therapies for children with bilateral disease, the resultant visual impairment, cosmetic deformity and risk for new tumors result in morbidity to these children who otherwise have a near normal lifespan. Therefore, since 1994, chemoreduction with vincristine, carboplatin, and etoposide combined with focal treatment, have been used successfully. However, a major concern with the use of carboplatin has been ototoxicity. PROCEDURES: To determine whether carboplatin, in the doses and schedule used by us and others to treat retinoblastoma (18.6 mg/kg q 4 weeks for six cycles) results in hearing impairment, we reviewed the records of 248 children with retinoblastoma, 164 of whom had received carboplatin. Children generally received carboplatin, vincristine, and etoposide (CEV) for six cycles of chemotherapy. RESULTS: Hearing evaluations prior to initiating therapy were abnormal in 14 patients (5.6%). No patients with normal initial audiograms were found to have abnormal studies following repeated evaluations. CONCLUSION: While ototoxicity is a potential concern in this young patient population, carboplatin in the treatment of retinoblastoma does not appear to produce impairment. Screening can identify children who require frequent audiologic follow-up, but children whose hearing is normal prior to therapy do not require routine surveillance following six cycles of standard CEV therapy. PMID- 17278121 TI - Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children's Oncology Group phase II study. AB - BACKGROUND: The prognosis for children with brain stem glioma remains grim. Based on studies suggesting efficacy of vincristine and oral VP-16, The Pediatric Oncology Group (POG, now part of the Children's Oncology Group) conducted a study using these agents in combination with standard external beam radiation for children with newly diagnosed brain stem glioma. METHODS: Children were eligible for the study if they 3-21 years of age, had MRI-evidence of a diffuse intrinsic pontine glioma, and had neurologic deficits of <6 months duration. Patients received local radiotherapy to a dosage of 54 Gy. Chemotherapy consisted of two 28-day cycles of vincristine, 1.5 mg/m(2), days 1, 8, and 15 and oral VP-16, 50 mg/m(2), days 1-21, starting concurrent with radiation, and continuing for ten cycles following radiation. RESULTS: Of the 31 children enrolled, 30 were eligible and evaluable for survival and toxicity. Their median age was 8 years (range 3-14 years). Seven patients (23%) had a partial response following radiation, 18 (60%) had stable disease, 2 (7%) had progressive disease, and response in 3 patients (10%) was not measured. All 30 children have died. Overall survival at 1 year was 27 +/- 7% and at 2 years, 3 +/- 2%. The median survival was 9 months (range 3-36 months). Hematologic toxicity was significant; other toxicities included constipation, mucositis, emesis, and infection. CONCLUSION: The addition of vincristine and oral VP-16 to standard external beam radiation causes moderate toxicity and does not improve survival of children with diffuse intrinsic brain stem glioma. PMID- 17278122 TI - Bone marrow necrosis as a presenting feature of childhood acute lymphoblastic leukemia. PMID- 17278123 TI - Successful treatment with modified CHOP-rituximab in pediatric AIDS-related advanced stage Burkitt lymphoma. AB - Burkitt lymphoma is the most common AIDS-related lymphoma (ARL) in childhood. The major issues in adult and pediatric ARL include identifying the optimal chemotherapy regimen and the concurrent treatment of both rituximab and highly active anti-retroviral therapy (HAART). We present a case of advanced stage Burkitt lymphoma in an 8-year-old female with acquired immunodeficiency syndrome (AIDS), who was successfully treated with a 3 month course of modified CHOP-R (cyclophosphamide, daunorubicin, vincristine, prednisone, and rituximab) and HAART therapy. The combination of rituximab and chemotherapy with HAART therapy may be well-tolerated and effective in HIV/AIDS patients with Burkitt lymphoma. PMID- 17278124 TI - Recent progress in the field of glycopeptide synthesis. AB - Glycosylation is a common post-translational modification of proteins. Although its significance in biological system is well recognized, approaches to analyze carbohydrate function are limited. This is because of difficulty in obtaining homogeneous glycoproteins from natural sources. Due to the progress of the carbohydrate and peptide chemistry, syntheses of various homogeneous glycopeptides and glycoproteins, which are suitable for biological studies, have been achieved by chemical means. In this review, we briefly summarize recent advances in the field of glycopeptide synthesis after 1999. PMID- 17278125 TI - Neuromuscular junction in abdominal muscles of Drosophila melanogaster during adulthood and aging. AB - The neuromuscular junction (NMJ) of Drosophila melanogaster has been established as a productive model for the study of synaptogenesis, synaptic plasticity, vesicle recycling, and other synaptic functions in embryos and larvae. It also has potential for the study of long-term plasticity during adult life and degenerative processes associated with aging. Here we provide a detailed description of the morphology and ultrastructure of the NMJ on abdominal dorsal longitudinal muscles throughout adult life from eclosion to senescence. In contrast to the case in the larva, the predominant type of terminals in these muscles in the adult fly consists of only two or three branches with tightly packed synaptic boutons. We observed qualitative and quantitative changes as mean bouton size increased gradually during adulthood, and the largest boutons were present in the old fly. The length of nerve branches first increased and thereafter decreased gradually during most of adult life. Branch diameter also decreased progressively, but branch number did not change. The subsynaptic reticulum became progressively thinner, and "naked" boutons were found in old flies. Ultrastructural traits gave indications of an age-associated increment in autophagy, larger synaptic vesicles, and impaired endocytosis. We propose that NMJ aging in the fly correlates with impaired endocytosis and membrane dynamics. This view finds a functional correlate in flies carrying a temperature-sensitive mutation in shibire that reversible blocks endocytosis; age significantly reduces the time required for complete paralysis and increases the time of recovery, thus confirming the age-dependent alteration in vesicle dynamics. PMID- 17278126 TI - Role of ASCA and the NOD2/CARD15 mutation Gly908Arg in predicting increased surgical costs in Crohn's disease patients: a project of the European Collaborative Study Group on Inflammatory Bowel Disease. AB - BACKGROUND: NOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD. METHODS: CD patients in a prospectively designed community-based multinational European and Israeli cohort (n = 228) followed for mean 8.3 (SD 2.6) years had blood drawn for measurement of ASCA (IgG, IgA), Arg702Trp, Gly908Arg, and Leu1007fsinsC. Days spent in the hospital and the costs of medical and surgical hospitalizations and medications were calculated. RESULTS: The median duration of surgical hospitalizations was longer in Gly908Arg-positive than -negative patients, 3.5 and 1.5 days/patient-year (P < 0.01), and in ASCA-positive than -negative patients, 1.1 and 0 days/patient-year (P < 0.001). Median surgical hospitalization cost was 1,580 euro/patient-year in Gly908Arg-positive versus 0 euro/patient-year in -negative patients (P < 0.01), and 663 euro/patient-year in ASCA-positive versus 0 euro/patient-year in negative patients (P < 0.001). Differences in cost of medications between groups were not significant. The effect of Gly908Arg was expressed in countries with higher Gly908Arg carriage rates. ASCA raised surgical costs independently of the age at diagnosis of disease. Arg702Trp and Leu1007fsinsC did not affect the cost of health care. CONCLUSIONS: Since CD patients positive for Gly908Arg and ASCA demonstrated higher health care costs, it is possible that measurement of Gly908Arg and ASCA at disease diagnosis can forecast the expensive CD patients. PMID- 17278127 TI - Hypokalemia associated with infliximab: a pharmacovigilance perspective. PMID- 17278128 TI - Corticofugal modulation of acoustically induced Fos expression in the rat auditory pathway. AB - To investigate the corticofugal modulation of acoustic information ascending through the auditory pathway of the rat, immunohistochemical techniques were used to study the functional expression of Fos protein in neurons. With auditory stimulation at different frequencies, Fos expression in the medial geniculate body (MGB), inferior colliculus (IC), superior olivary complex, and cochlear nucleus was examined, and the extent of Fos expression on the two sides was compared. Strikingly, we found densely Fos-labeled neurons in all divisions of the MGB after both presentation of an auditory stimulus and administration of a gamma-aminobutyric acid type A (GABA(A)) antagonist (bicuculline methobromide; BIM) to the auditory cortex. The location of Fos-labeled neurons in the ventral division (MGv) after acoustic stimulation at different frequencies was in agreement with the known tonotopic organization. That no Fos-labeled neurons were found in the MGv with acoustic stimuli alone suggests that the transmission of ascending thalamocortical information is critically governed by corticofugal modulation. The dorsal (DCIC) and external cortices (ECIC) of the IC ipsilateral to the BIM-injected cortex showed a significantly higher number of Fos-labeled neurons than the contralateral IC. However, no difference in the number of Fos labeled neurons was found between the central nucleus of the IC on either side, indicating that direct corticofugal modulation occurs only in the ECIC and DCIC. Further investigations are needed to assess the functional implications of the morphological differences observed between the descending corticofugal projections to the thalamus and the IC. PMID- 17278129 TI - Severe ulcerative colitis complicated by an arterial thrombus in the brachiocephalic trunk. PMID- 17278130 TI - Differential distribution of the MeCP2 splice variants in the postnatal mouse brain. AB - Mutations in the gene encoding methyl CpG binding protein 2 (MeCP2) are the primary cause of the neurodevelopmental disorder Rett syndrome (RTT). Mecp2 deficient mice develop a neurological phenotype that recapitulates many of the symptoms of RTT, including postnatal onset of the neurological deficits. MeCP2 has two isoforms, MeCP2e1 and MeCP2e2, with distinct amino termini, which are generated by alternative splicing. We examined the distribution of the Mecp2 splice variants in the postnatal mouse brain by in situ hybridization and found regional and age-related differences in transcript abundance. In newborn mice, signals for total Mecp2 and the Mecp2e2 transcripts were widely distributed, with overlapping expression patterns throughout the brain. Expression of the Mecp2e2 splice variant became largely restricted to nuclei within the dorsal thalamus (DT) and cortical layer V in juvenile animals, a pattern that was maintained into adulthood. In contrast, the total Mecp2 riboprobe only weakly labeled the DT and cortical layer V in juvenile and adult animals, although it heavily labeled surrounding brain regions, suggesting that Mecp2e1 is the predominant transcript outside the thalamus. Quantitative real-time PCR was used to measure Mecp2e1 and Mecp2e2 abundance in the diencephalon of adult mice, demonstrating significantly more Mecp2e2 in the DT than in the hypothalamus, which is in agreement with the Mecp2e2 in situ hybridization. The differential distribution of the Mecp2e1 and Mecp2e2 transcripts indicates regional and developmental regulation of Mecp2 splicing in the postnatal mouse brain. PMID- 17278131 TI - Differential hypertrophy and atrophy among all types of cutaneous innervation in the glabrous skin of the monkey hand during aging and naturally occurring type 2 diabetes. AB - Diabetic neuropathy (DN) is a common severe complication of type 2 diabetes. The symptoms of chronic pain, tingling, and numbness are generally attributed to small fiber dysfunction. However, little is known about the pathology among innervation to distal extremities, where symptoms start earliest and are most severe, and where the innervation density is the highest and includes a wide variety of large fiber sensory endings. Our study assessed the immunochemistry, morphology, and density of the nonvascular innervation in glabrous skin from the hands of aged nondiabetic rhesus monkeys and from age-matched monkeys that had different durations of spontaneously occurring type 2 diabetes. Age-related reductions occurred among all types of innervation, with epidermal C-fiber endings preferentially diminishing earlier than presumptive Adelta-fiber endings. In diabetic monkeys epidermal innervation density diminished faster, became more unevenly distributed, and lost immunodetectable expression of calcitonin gene related peptide and capsaicin receptors, TrpV1. Pacinian corpuscles also deteriorated. However, during the first few years of hyperglycemia, a surprising hypertrophy occurred among terminal arbors of remaining epidermal endings. Hypertrophy also occurred among Meissner corpuscles and Merkel endings supplied by Abeta fibers. After longer-term hyperglycemia, Meissner corpuscle hypertrophy declined but the number of corpuscles remained higher than in age-matched nondiabetics. However, the diabetic Meissner corpuscles had an abnormal structure and immunochemistry. In contrast, the expanded Merkel innervation was reduced to age-matched nondiabetic levels. These results indicate that transient phases of substantial innervation remodeling occur during the progression of diabetes, with differential increases and decreases occurring among the varieties of innervation. PMID- 17278132 TI - Vestibular neurons in the rat contain imidazoleacetic acid-ribotide, a putative neurotransmitter involved in blood pressure regulation. AB - A substantial body of research has led to the recognition that the vestibular system participates in blood pressure modulation during active movements and changes in posture, and that this modulation is effected at least partly by the caudal vestibular nuclei. The I-4 isomer of imidazoleacetic acid-ribotide (IAA RP) is a putative neurotransmitter/modulator that is thought to be an endogenous regulator of general sympathetic drive, particularly systemic blood pressure. The present study employed immunofluorescence and light and electron microscopic immunocytochemistry to visualize IAA-RP in the vestibular nuclei of adult male rats. The results demonstrate IAA-RP immunolabeling of subpopulations of vestibular neurons in the descending nucleus and the caudal half of the medial nucleus, with scattered immunostained vestibular neurons also present more rostrally. On the basis of double immunofluorescence staining for IAA-RP and calbindin, many of these ribotide-immunoreactive neurons appear to be innervated by cerebellar Purkinje cell afferents. Ultrastructural observations in the caudal vestibular nuclei confirm the IAA-RP immunolocalization in cell bodies and dendritic processes, and in some myelinated axons and presynaptic boutons. The regional distribution of IAA-RP immunoreactivity corresponds to the location of vestibular neurons involved in autonomic functions. The presence of IAA-RP in those neurons suggests that they participate specifically in vestibulo-autonomic regulation of blood pressure. The localization of immunostain in processes and terminals suggests that vestibulo-autonomic activity is subject to local feedback control. Overall, the observations offer a chemoanatomic basis for understanding the vestibular side effects commonly experienced by patients treated with clonidine and other imidazoline-related drugs. PMID- 17278133 TI - Skeletal morphology and postmetamorphic ontogeny of Acris crepitans (Anura: Hylidae): a case of miniaturization in frogs. AB - Acris crepitans is a small, semiaquatic member of the treefrog family Hylidae. Much recent attention has been paid to this species because of reports of population declines and malformations, yet few works have considered the skeletal anatomy of this common North American frog. Herein, we provide a detailed description of the morphology and adult ontogeny of the skeleton of A. crepitans, and discuss novel morphologies, interesting postmetamorphic developmental patterns, and intraspecific skeletal variation. The reduced amount of adult ossification, as well as several novel morphologies present in this species, are consistent with patterns of miniaturization seen in other anurans. For example, the skull is poorly ossified, but most of the cranial cartilages are heavily mineralized, the nasal bones are fused to endochondral ossification of the tectum nasi, the palatines are reduced, and the prootics and exoccipitals are not fused to one another (although the prootics are well-developed and ornamented). In addition, several specimens exhibit abnormalities, which might indicate that: (1) the population was under an acute malformation outbreak, (2) a high incidence of small skeletal malformations is normal in this species, (3) the population is under stress because of habitat fragmentation, (4) there is environmental deterioration in the region where the specimens were collected, and/or (5) the species is now showing signs of decline in southern Missouri. Regardless of the cause, it is clear that further examination of skeletal variability in A. crepitans, including ossification patterns and the frequency of abnormalities, is warranted. PMID- 17278134 TI - Morphology, constraints, and scaling of frontal sinuses in the hartebeest, Alcelaphus buselaphus (Mammalia: Artiodactyla, Bovidae). AB - The frontal sinuses of bovid mammals display a great deal of diversity, which has been attributed to both phylogenetic and functional influences. In-depth study of the hartebeest (Alcelaphus buselaphus), a large African antelope, reveals a number of previously undescribed details of frontal sinus morphology. In A. buselaphus, the frontal sinuses conform closely to the shape of the frontal bone, filling nearly the entire element. However, the horncores are never extensively pneumatized, contrasting with the condition seen in many other bovids. This evidence is inconsistent with the hypothesis that sinuses are opportunistic pneumatizing agents, suggesting that phylogenetic factors also play a role in determining sinus size. Both cranial sutures and neurovasculature appear to constrain the growth of sinuses in part. In turn, the sinus also affects the growth of the parietal; apparently this element is not truly pneumatized by the sinus in most cases, but the bone's shape changes under the influence of the sinus. Furthermore, the sinuses present relatively few struts when compared with the sinuses of some other bovids, such as Ovis. By adapting methods previously developed for measuring structural parameters of trabecular bone, it is possible to quantify certain aspects of sinus morphology. These include the number of bony struts within the sinus, the spacing of these struts, and the size of individual cavities within the sinus. Some differences in the number of struts are evident between subspecies. Similarly, significant differences occur in the relative number of struts between male and female A. buselaphus, which may be related to behavior. The volume of the sinus is strongly correlated with the size of the frontal, but less so with overall cranial size. This finding illustrates the importance of choosing variables carefully when comparing sinus sizes and growth between species. PMID- 17278135 TI - Localization of TrkC to Schwann cells and effects of neurotrophin-3 signaling at neuromuscular synapses. AB - Neurotrophins and their receptors, the Trks, are differentially expressed among the cell types that make up neuromuscular and other synapses, but the function and directionality of neurotrophin signaling at synapses are poorly understood. Here we demonstrate, via immunostaining, Western blotting, and RT-PCR analyses, that TrkC, the receptor for neurotrophin-3 (NT3), is expressed by mouse perisynaptic and myelinating Schwann cells from birth through adulthood and is unaltered after denervation. Analyses of transgenic mice in which the NT3 coding sequence is replaced by lacZ showed that NT3 is expressed in motor neurons and Schwann cells during perinatal development, but not in adult mice. In muscle, NT3 is expressed by intrafusal muscle fibers within spindles, as has been previously reported. Surprisingly, NT3 is also expressed in extrafusal muscle fibers during perinatal life and in adults. Genetic approaches were used to explore the roles of NT3 and TrkC signaling at neuromuscular synapses. Overexpression of NT3 in muscle fibers during development resulted in an increased number of perisynaptic Schwann cells at neuromuscular synapses, without altering synaptic size, suggesting that muscle-derived NT3 might act as a mitogen or trophic factor for Schwann cells. Conditional deletion of NT3 from motor neurons did not alter the number of Schwann cells or other aspects of neuromuscular synaptic structure, suggesting that motor-neuron-derived NT3 is not required for normal development of perisynaptic Schwann cells or synapses. Together, these results demonstrate that NT3 expression is developmentally regulated in skeletal muscle and may modulate the number of Schwann cells at neuromuscular synapses. PMID- 17278136 TI - Cadherin expression in the developing mouse olfactory system. AB - Although odor receptors have been implicated in establishing the topography of olfactory sensory neurons (OSNs) in the olfactory bulb (OB), it is likely other molecules are also involved. The cadherins (CDHs) are a large family of cell adhesion molecules that mediate cell:cell interactions elsewhere in the central nervous system. However, their distribution and role in the olfactory system have remained largely unexplored. We previously demonstrated that intracellular binding partners of cadherins, the catenins, have unique spatiotemporal patterns of expression in the developing olfactory system. To further our understanding of cadherin function within the developing olfactory system, we now report on the localization of 11 classical cadherins-CDH1, 2, 3, 4, 5, 6, 8, 10, 11, 13, and 15. We demonstrate the expression of all but CDH5 and CDH15 in neuronal and/or glial cells in primary olfactory structures. CDH1 and CDH2 are expressed by OSNs; CDH2 expression closely parallels that seen for gamma-catenin in OSN axons. CDH3 and CDH11 are expressed by olfactory ensheathing glia, which surround OSN axons in the outer OB. CDH2, CDH4, and CDH6 are expressed within neuropil. CDH2, CDH4, CDH6, CDH8, CDH10, CDH11, and CDH13 are expressed by projection neurons within the main and accessory OBs. We conclude that cadherin proteins in the developing olfactory system are positioned to underlie the formation of the odorant map and local circuits within the OB. PMID- 17278137 TI - Fiber connections of the corpus glomerulosum pars rotunda, with special reference to efferent projection pattern to the inferior lobe in a percomorph teleost, tilapia (Oreochromis niloticus). AB - Fiber connections of the corpus glomerulosum pars rotunda (GR) in a teleost, tilapia Oreochromis niloticus, were studied by biotinylated dextran amine injections into the GR and inferior lobe. After tracer injections into the GR, major groups of labeled somata were found bilaterally in the cortical nucleus and ipsilaterally in the nucleus intermedius. Numerous labeled terminals were found ipsilaterally in the central nucleus, nucleus of lateral recess, and diffuse nucleus (NDLI) of the inferior lobe. Some other connections were also elucidated in the present study, although these were less abundant. Notably, efferent projections to the inferior lobe were not evenly distributed within each lobar nucleus. Labeled terminals were confined to the cell body zone of central nucleus and the outer cell-sparse layer of the nucleus of lateral recess. The rostrolateral portion of NDLI and ventrolateral portion of middle to caudal NDLI received few GR fibers, the rostromedial portion of NDLI a moderate density of fibers, and the rest of the nucleus numerous fibers. These different portions of the NDLI, to some extent, also differed in other afferent and efferent connections, suggesting regional specialization of the nucleus. Furthermore, restricted injections to the lobar nuclei suggest different efferent projections of the component cells of the GR: large and small cells. The large cells project only to the central nucleus, whereas the small cells project to the NDLI and nucleus of lateral recess. Therefore, the two types of GR cells appear to constitute parallel pathways from the pretectum to the inferior lobe. PMID- 17278138 TI - Noradrenergic axon terminals contact gastric preautonomic neurons in the paraventricular nucleus of the hypothalamus in rats. AB - Hypothalamic neural activity is modulated by viscerosensory signals that are carried in large part by noradrenergic (NA) inputs to the paraventricular nucleus of the hypothalamus (PVN). The present study examined the ultrastructural relationship of NA axon varicosities with the somata and dendrites of identified gastric preautonomic PVN neurons in adult male rats. NA varicosities were visualized by immunoperoxidase labeling of dopamine beta hydroxylase (DbH), and gastric preautonomic PVN neurons were identified by immunogold labeling of pseudorabies virus (PRV) transported retrogradely and transneuronally from injection sites in the stomach wall. Among 1,136 DbH-positive varicosities identified within the parvocellular PVN in four rats, approximately 36% formed either a close apposition or a synaptic contact with a somatic or dendritic profile. The majority of identified contacts between DbH- and PRV-positive profiles were classified as close appositions that lacked clear synaptic specializations. Approximately 65% of identified synaptic contacts between DbH- and PRV-positive profiles were classified as symmetric (Gray's type II) synapses. DbH-positive terminals formed close appositions and synaptic contacts with dendritic and somatic compartments of PRV-positive neurons, although dendrites were contacted nearly five times more often than somata. These findings invite continued work to delineate the functional role of NA signaling pathways in conveying interoceptive signals to preautonomic PVN neurons under normal and pathophysiological conditions. PMID- 17278139 TI - Decreased neurogenesis in aged rats results from loss of granule cell precursors without lengthening of the cell cycle. AB - It is well established that neurogenesis in the dentate gyrus slows with aging, but it is unclear whether this change is due to slowing of the cell cycle, as occurs during development, or to loss of precursor cells. In the current study, we find that the cell cycle time of granule cell precursors in middle-aged male rats is not significantly different from that in young adults. The size of the precursor pool, however, was 3-4 times smaller in the middle-aged rats, as determined using both cumulative bromodeoxyuridine (BrdU) labeling as well as labeling with the endogenous marker of cell proliferation, proliferating cell nuclear antigen (PCNA). Loss of precursor cells was much greater in the granule cell layer than in the hilus, suggesting that dividing cells in the hilus belong to a distinct population, most likely glial progenitors, that are less affected by aging than neuronal precursors. BrdU-labeled precursor cells and young neurons, labeled with doublecortin, appeared to be lost equally from rostral and caudal, as well as suprapyramidal and infrapyramidal, subregions of the granule cell layer. However, doublecortin staining did show large parts of the caudal granule cell layer with few if any young neurons at both ages. Taken together, these findings indicate that precursor cells are not distributed evenly within the dentate gyrus in adulthood but that precursors are lost from throughout the dentate gyrus in old age with no concomitant change in the cell cycle time. PMID- 17278140 TI - Purkinje cell compartmentation as revealed by zebrin II expression in the cerebellar cortex of pigeons (Columba livia). AB - Purkinje cells in the cerebellum express the antigen zebrin II (aldolase C) in many vertebrates. In mammals, zebrin is expressed in a parasagittal fashion, with alternating immunopositive and immunonegative stripes. Whether a similar pattern is expressed in birds is unknown. Here we present the first investigation into zebrin II expression in a bird: the adult pigeon (Columba livia). Western blotting of pigeon cerebellar homogenates reveals a single polypeptide with an apparent molecular weight of 36 kDa that is indistinguishable from zebrin II in the mouse. Zebrin II expression in the pigeon cerebellum is prominent in Purkinje cells, including their dendrites, somata, axons, and axon terminals. Parasagittal stripes were apparent with bands of Purkinje cells that strongly expressed zebrin II (+ve) alternating with bands that expressed zebrin II weakly or not at all ( ve). The stripes were most prominent in folium IXcd, where there were seven +ve/ ve stripes, bilaterally. In folia VI-IXab, several thin stripes were observed spanning the mediolateral extent of the folia, including three pairs of +ve/-ve stripes that extended across the lateral surface of the cerebellum. In folium VI the zebrin II expression in Purkinje cells was stronger overall, resulting in less apparent stripes. In folia II-V, four distinct +ve/-ve stripes were apparent. Finally, in folia I (lingula) and X (nodulus) all Purkinje cells strongly expressed zebrin II. These data are compared with studies of zebrin II expression in other species, as well as physiological and neuroanatomical studies that address the parasagittal organization of the pigeon cerebellum. PMID- 17278141 TI - Murine model of prosthesis failure for the long-term study of aseptic loosening. AB - We examined a novel mouse model of wear debris-induced prosthesis instability and osteolysis, and its application for the evaluation of therapy. A stainless steel or titanium-alloy pin was implanted into the proximal tibia to form a contiguous surface with the articular cartilage. In some mice, titanium particles were injected into the tibial canal during the surgery, followed by monthly intraarticular injection. MicroCT scans revealed that the implants without particle challenge were stable without bone mineral density changes for 6 months. Histological analysis showed new bone formation around the implant at 6 weeks postsurgery. Periprosthetic soft tissue with inflammatory cells was a ubiquitous finding at the interface between the implant and surrounding bone in samples exposed to titanium particles, and expression of IL-1beta, TNFalpha, and CD68 was common in these joints. Pullout tests indicated that an average 5N load was required to pull out stable implants from surrounding bone. However, particle stimulation dramatically reduced the pullout force to less than 0.4 N. The feasibility of in vivo gene transfer on this model was confirmed by X-gal staining of synovial membrane and periprosthetic tissue after injection of AAV LacZ in the prosthetic joint. This murine model of weight-bearing knee prosthesis provides an economical, reproducible, and easily obtained means to study joint arthroplasty failure. The ability to evaluate the biomechanical properties of the prosthetic joint, in addition to histological and biochemical examination, results in a useful model to investigate many of the properties of prosthetic joint components during the response to debris-associated osteolysis. PMID- 17278143 TI - Retinotectal ganglion cells in the zebrafish, Danio rerio. AB - The morphology of retinotectal ganglion cells was investigated by retrograde transport of dextran amines applied into the optic tectum in vitro. Based on criteria such as stratification pattern and size of the dendritic processes, as well as the shape and position of the soma within the dendritic field, three main groups of ganglion cell types with a total of nine different types were identified. The first group included monostratified cells, of which two types (Ma(2) and Mb(5)) may be ON- and OFF-variants, and the third (Mb(6)) had its dendritic field as a narrow band at the inner border of the inner plexiform layer. These three cells had the largest dendritic fields, with areas exceeding 40,000 microm(2). In two additional monostratified cells the dendrites were spread over the entire width of either sublamina a or sublamina b of the inner plexiform layer (Ma, Mb). They were of intermediate size with mean dendritic field areas between 10,000 and 20,000 microm(2). The second group contained two types of bistratified cells (Bb(4/5) and Bb(4,5/5,6)) with two distinct bands of dendritic stratifications in sublamina b. One of them had the smallest dendritic field (below 5,000,mm(2)) of all cell types in the sample. The diffuse cells of the third group had their dendrites across the entire width of the inner plexiform layer. The sample of retinotectal cells investigated in this study included types described previously (Mangrum et al. [2002] Vis Neurosci 19:767 779) but also new types not described previously. PMID- 17278142 TI - Differential expression of class 3 and 4 semaphorins and netrin in the lamprey spinal cord during regeneration. AB - To explore the role of axon guidance molecules during regeneration in the lamprey spinal cord, we examined the expression of mRNAs for semaphorin 3 (Sema3), semaphorin 4 (Sema4), and netrin during regeneration by in situ hybridization. Control lampreys contained netrin-expressing neurons along the length of the spinal cord. After spinal transection, netrin expression was downregulated in neurons close (500 mum to 10 mm) to the transection at 2 and 4 weeks. A high level of Sema4 expression was found in the neurons of the gray matter and occasionally in the dorsal and the edge cells. Fourteen days after spinal cord transection Sema4 mRNA expression was absent from dorsal and edge cells but was still present in neurons of the gray matter. At 30 days the expression had declined to some extent in neurons and was absent in dorsal and edge cells. In control animals, Sema3 was expressed in neurons of the gray matter and in dorsal and edge cells. Two weeks after transection, Sema3 expression was upregulated near the lesion, but absent in dorsal cells. By 4 weeks a few neurons expressed Sema3 at 20 mm caudal to the transection but no expression was detected 1 mm from the transection. Isolectin I-B(4) labeling for microglia/macrophages showed that the number of Sema3-expressing microglia/macrophages increased dramatically at the injury site over time. The downregulation of netrin and upregulation of Sema3 near the transection suggests a possible role of netrin and semaphorins in restricting axonal regeneration in the injured spinal cord. PMID- 17278144 TI - Reporting birth defects surveillance data 1968-2003. PMID- 17278150 TI - Effects of hyperbaric oxygen treatment on tendon graft and tendon-bone integration in bone tunnel: biochemical and histological analysis in rabbits. AB - Despite moderate success in clinical applications, outcome of tendon grafts employed for anterior cruciate ligament (ACL) reconstruction remains unsatisfactory. This study investigated the effects of hyperbaric oxygen (HBO) on neovascularization at the tendon-bone junction, collagen fibers of the tendon graft, and the tendon graft-bony interface incorporated into the osseous tunnel in rabbits. Forty rabbits were assigned to two groups. The HBO group was exposed to 100% oxygen at 2.5 atmospheres pressure for 2 h daily, 5 consecutive days in a week. The control group was maintained in cages exposed to normal air. Histological studies of 12 rabbits were performed postoperatively at 6, 12, and 18 weeks. Biomechanical studies of 24 rabbits were conducted postoperatively at 12 and 18 weeks. Electron microscopy (EM) analyses of four rabbits were performed postoperatively at 18 weeks. Experimental results demonstrated that a higher number of Sharpey's fibers bridged the newly formed fibrocartilage and graft in the HBO group than in the control group. In addition, HBO treatment increased neovascularization and enhanced the incorporation of the progressive interface between tendon graft and bone. Biomechanical analysis showed that the HBO group achieved higher maximal pullout strength than the control group. Examination by EM showed that HBO treatment resulted in regenerated collagen fibers with increased compaction and regularity. Based on experimental results, HBO treatment is a treatment modality that potentially improves outcome following ACL reconstruction. PMID- 17278151 TI - Astrocytic hypertrophy in dysmyelination influences the diffusion anisotropy of white matter. AB - The effect of a proteolipid protein (PLP) mutation on the developing white matter anisotropy was examined by diffusion tensor magnetic resonance imaging (DT-MRI) in a noninvasive study of a mouse model of Pelizaeus-Merzbacher disease (PMD). The jimpy PLP mutation in mice produces an irreversible dysmyelination in jimpy males, whereas heterozygous females exhibit a transient hypomyelination, as assessed by a longitudinal study of the same mice during development. Modifications of the different individual DT-MRI parameters were highlighted by specific changes in tissue structures caused by the mutation that includes the hypomyelination, axonal abnormalities, and recovery. Astrocytic hypertrophy is a striking cellular event in dysmyelinated jimpy brain, where most axons or bundles of fibers are entirely wrapped by astrocyte cytoplasmic processes, so its influences on DT-MRI parameters in dysmyelination were examined for the first time. DT-MRI data of the jimpy brain were compared with those obtained from dysmyelination of (oligo-TTK) transgenic mice, induced by oligodendrocyte killing, which have a mild astrocyte hypertrophy (Jalabi et al., 2005), and from recovering jimpy females, which have reduced astrocyte hypertrophy. The unique morphological feature of astrocytes in jimpy males coupled with an increase in the water channel protein aquaporin 4 (AQP4) was found to facilitate the directional water diffusion in the white matter. In addition to the major changes of DT-MRI parameters in the two dysmyelinated mice caused by the myelin loss and axonal modifications, the amplified magnitude of radial and axial diffusions in jimpy males was attributed principally to the strongly pronounced astrocyte hypertrophy. PMID- 17278152 TI - Ifosfamide neuropsychiatric toxicity in patients with cancer. AB - Ifosfamide is a chemotherapy agent commonly used in the treatment of several solid tumors and hematologic malignancies. Common ifosfamide toxicities are bone marrow suppression, alopecia, nausea and vomiting. Less common, but striking, are the rare but dramatic neuropsychiatric toxicities with discrete neurological symptoms and delirium. We report here a case of ifosfamide neuropsychiatric toxicity which presented with an isolated psychotic disorder with delusions, and was successfully treated with methylene blue. Current literature on treatment and prophylaxis of this clinically challenging chemotherapy-induced complication is presented. PMID- 17278153 TI - Psychological adjustment of survivors of localised prostate cancer: investigating the role of dyadic adjustment, cognitive appraisal and coping style. AB - OBJECTIVES: The aim of this study was to identify the factors that contribute to psychological adjustment in prostate cancer patients two or more years post treatment. METHOD: One hundred and sixty-seven men who had undergone treatment for localised prostate cancer participated in this study. In the sample 63 participants had undergone external beam radiotherapy (EBRT), 55 radical prostatectomy (RP), 27 EBRT plus hormone therapy (EBRT/HT), and the remainder a combination of treatments. Patients completed the UCLA-PCI, the POMS, CISS, DAS and a threat appraisal questionnaire. RESULTS: The majority of patients reported relatively positive adjustment in most domains except sexual functioning. For those who reported ongoing psychological difficulty mood disturbance was associated with sexual bother, dyadic adjustment, threat appraisal, self-efficacy appraisal and emotion-focussed coping. Lower levels of urinary bother were associated with the use of more task-focussed coping. Emotion-focussed coping and threat appraisal mediated the relationship between sexual bother and mood disturbance. Emotion-focussed coping moderated the influence of dyadic adjustment on mood disturbance. CONCLUSIONS: Dyadic adjustment, threat appraisal and coping style play a significant role in the long-term psychological adjustment of prostate cancer patients. The results of the current study indicate that the use of emotion-focussed coping to manage sexual bother appears to result in poor psychological adjustment, which indicates the need for further education or intervention to manage sexual dysfunction. ETHICS CLEARANCE: Human ethics approval was granted from Southern Health, Peter MacCallum Cancer Centre and the Monash University Ethics Committee before commencement of data collection. PMID- 17278154 TI - PCI without on-site surgical backup. PMID- 17278155 TI - The current status and future direction of percutaneous coronary intervention without on-site surgical backup: an expert consensus document from the Society for Cardiovascular Angiography and Interventions. PMID- 17278156 TI - Supramolecular aggregates of dendritic multishell architectures as universal nanocarriers. PMID- 17278160 TI - Magnetic nanoparticles: synthesis, protection, functionalization, and application. AB - This review focuses on the synthesis, protection, functionalization, and application of magnetic nanoparticles, as well as the magnetic properties of nanostructured systems. Substantial progress in the size and shape control of magnetic nanoparticles has been made by developing methods such as co precipitation, thermal decomposition and/or reduction, micelle synthesis, and hydrothermal synthesis. A major challenge still is protection against corrosion, and therefore suitable protection strategies will be emphasized, for example, surfactant/polymer coating, silica coating and carbon coating of magnetic nanoparticles or embedding them in a matrix/support. Properly protected magnetic nanoparticles can be used as building blocks for the fabrication of various functional systems, and their application in catalysis and biotechnology will be briefly reviewed. Finally, some future trends and perspectives in these research areas will be outlined. PMID- 17278161 TI - Azoporphyrin: the porphyrin analogue of azobenzene. PMID- 17278162 TI - Reactions of iminium ions with Michael acceptors through a Morita-Baylis-Hillman type reaction: enantiocontrol and applications in synthesis. PMID- 17278163 TI - Chiral Bronsted acids in the catalytic asymmetric Nazarov cyclization--the first enantioselective organocatalytic electrocyclic reaction. PMID- 17278165 TI - Dynamics of thiolate chains on a gold nanoparticle. PMID- 17278164 TI - Batchwise growth of silica cone patterns via self-assembly of aligned nanowires. AB - Silica-cone patterns self-assembled from well-aligned nanowires are synthesized using gallium droplets as the catalyst and silicon wafers as the silicon source. The cones form a triangular pattern array radially on almost the whole surface of the molten Ga ball. Detailed field-emission scanning electron microscopy (SEM) analysis shows that the cone-pattern pieces frequently slide off and are detached from the molten Ga ball surface, which leads to the exposure of the catalyst surface and the growth of a new batch of silicon oxide nanowires as well as the cone patterns. The processes of growth and detachment alternate, giving rise to the formation of a volcano-like or a flower-like structure with bulk-quantity pieces of cone patterns piled up around the Ga ball. Consequently, the cone patterned layer grows batch by batch until the reaction is terminated. Different to the conventional metal-catalyzed growth model, the batch-by-batch growth of the triangular cone patterns proceeds on the molten Ga balls via alternate growth on and detachment from the catalyst surface of the patterns; the Ga droplet can be used continuously and circularly as an effective catalyst for the growth of amorphous SiO(x) nanowires during the whole growth period. The intriguing batchwise growth phenomena may enrich our understanding of the vapour-liquid solid (VLS) growth mechanism for the catalyst growth of nanowires or other nanostructures and may offer a different way of self-assembling novel silica nanostructures. PMID- 17278166 TI - Evolutionary shape control during colloidal quantum-dot growth. AB - Size-dependent optical properties of semiconductor nanocrystals are of great interest because of the myriad of phenomena stemming from them. The preparation of more complex colloidal shapes will facilitate the systematic study of shape dependent phenomena. It is shown that a strategy to obtain systematically more complex nanocrystal structures is to exert a sequence of shape-directing steps during the colloidal growth. Using experiments based on multiple reagent injections we show how changes in the type of surfactant introduced during growth of CdSe nanocrystals promotes shape evolution. On this basis, we propose a means to achieve a further generation of shape design in nanometer-sized colloids by using a series of growth steps, each one building from the previous conditions of shape as well as surface-specific reactivity. To understand the shape formation and stability in nanocrystalline colloids, and particularly the importance of surface ligands, we introduce an analogy with the thermodynamics of droplets. PMID- 17278167 TI - Estrogenic analogues synthesized by click chemistry. PMID- 17278168 TI - Effect of electron donors on the radical polymerization of vinyl acetate mediated by [Co(acac)2]: degenerative transfer versus reversible homolytic cleavage of an organocobalt(III) complex. AB - The molecular structure of bis(acetylacetonate)cobalt(II) ([Co(acac)2]) in solution and in the presence of the electron donors (ED) pyridine (py), NEt3, and vinyl acetate (VOAc) was investigated using 1H NMR spectroscopy in C6D6. The extent of formation of ligand adducts, [Co(acac)2(ED)x], varies in the order py>NEt3>VOAc (no interaction). Density functional theory (DFT) calculations on a model system agree with Co--ED bond strengths decreasing in the same order. The effect of electron donors on the [Co(acac)2]-mediated radical polymerization of VOAc was examined at 30 degrees C by the addition of excess py or NEt3 to the complex in the molar ratio [VOAc]0/[Co]0/[V-70]0/[py or NEt3]0=500:1:1:30 (V 70=2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile)). As previously reported by R. Jerome et al., the polymerization showed long induction periods in the absence of ED. However, a controlled polymerization without an induction period took place in the presence of ED, though the level of control was poorer. The effective polymerization rate decreased in the order py>NEt3. A similar behavior was found when these electron donors were added to an ongoing [Co(acac)2] mediated radical polymerization of VOAc. On the basis of the NMR and DFT studies, it is proposed that the polymerization is controlled by the reversible homolytic cleavage of an organocobalt(III) dormant species in the presence of ED. Conversely, the faster polymerization after the induction period in the absence of ED is due to a degenerative transfer process with the radicals produced by the continuous decomposition of the excess initiator. Complementary experiments provide additional results in agreement with this interpretation. PMID- 17278169 TI - The oxygen-bridge templating approach to eight- and nine-membered carbocycles: recent developments based on catalytic reactions. AB - Recent developments concerning metal-catalyzed reactions have led to the implementation of new, rapid, and practical routes to eight- and nine-membered carbocycles based on an oxygen-bridge templated cyclization. PMID- 17278170 TI - Site-specific DNA cleavage on a solid support: a method for mismatch detection. PMID- 17278171 TI - Copper-catalyzed cross-coupling reaction of grignard reagents with primary-alkyl halides: remarkable effect of 1-phenylpropyne. PMID- 17278172 TI - An enantioselective CpRu-catalyzed Carroll rearrangement. PMID- 17278173 TI - Second-trimester uterine artery Doppler pulsatility index and maternal serum PP13 as markers of pre-eclampsia. AB - OBJECTIVE: To evaluate whether measurement of maternal serum PP13 at 22 to 24 weeks of gestation, alone or in combination with second-trimester biochemical markers or uterine artery pulsatility measured by Doppler velocimetry, is useful in predicting those women at risk of developing pre-eclampsia. STUDY DESIGN: A nested case-control study of pre-eclampsia cases with controls matched for gestational age and storage time for the maternal serum. PP13 was tested by an ELISA, with the samples blinded to pregnancy outcome. All patients also underwent uterine artery Doppler flow velocimetry at 22-24 weeks to measure the mean pulsatility index (PI). Results for Inhibin, Activin, PAPP-A and Free beta-hCG were available from previous studies. RESULTS: There were 73 controls and five cases with early pre-eclampsia in which delivery was induced prior to 35 weeks. In addition, there were a further seven cases with pre-eclampsia in which delivery was not induced before term. Median PP13 levels for controls and all cases were 295.9 and 212.6 pg/ml, and 171.2 pg/ml amongst the early pre-eclampsia cases, with the MoMs 1.00, 0.94 and 0.63, respectively (p < 0.001). Receiver operator characteristic (ROC) curve analysis for either all cases or early cases versus controls yielded areas under the curve of 0.588 (95% CI: 0.42-0.76; p = 0.1526) and 0.693 (0.47-0.92; p = 0.0441) for PP13. At a specificity set to 0.80, the sensitivity for PP13 in the early cases was 0.40 and that in all cases was 0.25. Combining PP13 bivariately with any of the markers (PI, PAPP-A, Activin, Inhibin or Free beta-hCG) tested in the 22-24 week period did not improve the detection of early, late or all cases of pre-eclampsia compared with either marker alone. CONCLUSION: Late second-trimester PP13 alone is unlikely to be useful in predicting pre-eclampsia and early pre-eclampsia, and its prediction does not increase when coupled with second-trimester Doppler PI or other potential biochemical markers. Measuring between-trimester temporal changes may be worthy of further investigation. PMID- 17278174 TI - First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system. AB - BACKGROUND: PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. MATERIALS AND METHODS: PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (<1.5 kg), low birthweight (<2.5 kg), large birthweight (>4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group. Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. RESULTS: ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. CONCLUSIONS: The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and development by breaking down IGF binding proteins and causing the release of free IGF for uptake into cells to promote growth. In those cases that eventually result in poor fetal growth, levels of PAPP-A and ADAM12 at 11-14 weeks are significantly lower than normal-in this instance, lowered PAPP-A and ADAM12 would result in less free IGF being available for cell uptake and growth stimulation. Further studies may elucidate if screening using such modalities can lead to new potential treatments for poorly growing fetuses. PMID- 17278175 TI - Foetal magnetic resonance imaging and echogenic bowel. AB - OBJECTIVES: To evaluate how foetal magnetic resonance imaging (MRI) may change the diagnosis in cases of ultrasound (U/S) findings of echogenic bowel (EB). METHODS: Seventeen foetuses with EB underwent serial U/S examinations, foetal MRI, cystic fibrosis screening and maternal viral serologic tests. MRI protocol included T2-weighted half-Fourier acquired single-shot turbo spin-echo (HASTE) sequence and gradient echo (GE) T1-weighted images. Foetal abdominal MRI analyzed patterns were size and signal of small bowel, colon and rectum, ascites and abdominal mass. All neonates had complete clinical examination, abdominal sonography, and a 6 months clinical follow-up. RESULTS: Eleven foetuses with isolated EB had normal MRI and normal outcome. In comparison, all the 6 foetuses whose U/S patterns showed associated signs had abnormal MRI (p < 0.001). Five had proven pathology (83.3%: 5/6) and only 1 (16.7%: 1/6) had no proven pathology and normal postnatal outcome (p = 0.001). For those five, foetal MRI showed bowel abnormalities with one case of bowel duplication and four cases of bowel obstruction. Two out of the four cases of bowel obstruction were genetically diagnosed as cystic fibrosis. The two remaining cases were diagnosed as ileal atresia. CONCLUSION: MRI could provide additive information in cases of EB associated with bowel dilatation. PMID- 17278176 TI - Whole genome amplification from a single cell: a new era for preimplantation genetic diagnosis. AB - Preimplantation genetic diagnosis (PGD) is a technique used for determining the genetic status of a single cell biopsied from embryos or oocytes. Genetic analysis from a single cell is both rewarding and challenging, especially in PGD. The starting material is very limited and not replaceable, and the diagnosis has to be made in a very short time. Different whole genome amplification (WGA) techniques have been developed to specifically increase the DNA quantities originating from clinical samples with limited DNA contents. In this review, currently available WGA techniques are introduced and, among them, multiple displacement amplification (MDA) is discussed in detail. MDA generates abundant assay-ready DNA to perform broad panels of genetic assays through its ability to rapidly amplify genomes from single cells. The utilization of MDA for single-cell molecular analysis is expanding at a high rate, and MDA is expected to soon become an integral part of PGD. PMID- 17278177 TI - Isolated left-sided congenital diaphragmatic hernia: cardiac axis and displacement before fetal viability has no role in predicting postnatal outcome. AB - OBJECTIVES: The purpose of this retrospective study was to determine whether objective assessment of cardiac shifting on two-dimensional ultrasonography can predict postnatal outcome in fetuses with isolated left-sided congenital diaphragmatic hernia (CDH). MATERIALS AND METHODS: Still images at the level of the four-chamber view were obtained in 23 fetuses with left-sided CDH. A group of 12 fetuses (3 non-survivors and 9 survivors) were examined at two periods, between 20 and 30 weeks and between 31 and 40 weeks. A further 11 fetuses (2 non survivors and 9 survivors) were examined between 31 and 40 weeks. Fetal heart axis and position were determined manually and associated with postnatal outcome. RESULTS: The cardiac axis remained constant in the 9 survivors (15.5 +/- 3.2 versus 17.2 +/- 3.3, p = 0.71) and 3 non-survivors (19.0 +/- 11.5 versus 18.5 +/- 11.8, p = 0.97). There was no statistical difference between the 9 survivors and 3 non-survivors at the two periods. Cardiac displacement remained constant in the 9 survivors (0.2 +/- 0.02 versus 0.2 +/- 0.02, p = 0.32) but increased significantly in the 3 non-survivors (0.2 +/- 0.04 versus 0.4 +/- 0.02, p = 0.015). The difference between survivors and non-survivors was statistically significant between the18 survivors and 5 non-survivors examined between 31 and 40 weeks of gestation (0.2 +/- 0.02 versus 0.4 +/- 0.02, p = 0.037). CONCLUSION: This study does not support the hypothesis that objective assessment of mediastinal shift in fetuses with left-sided CDH has a role in predicting postnatal outcome before fetal viability, which is when it would be more useful for counseling patients regarding whether to continue with the pregnancy or to opt for termination. PMID- 17278178 TI - Unambiguous structural characterization of hydantoin reaction products using 2D HMBC NMR spectroscopy. AB - Data from two-dimensional (2D) NMR experiments were used to identify the reaction products resulting from the opening of pyroglutamates with isocyanates or thioisocyanates. The reaction has the potential to produce compounds that would have very similar one-dimensional proton ((1)H) or carbon-13 ((13)C) NMR spectra. Careful analysis of (1)H--(1)H COSY, (1)H--(1)H NOESY, and HMBC data, including chemical shifts and coupling constants, were used to distinguish correctly between carbamoyl-2-pyrrolidinone, hydantoin, and perhydro-1,3-diazepine-2,4 dione type structures that could result from this reaction. This work describes their preparation and subsequent identification using 2D NMR spectroscopy, and includes complete (13)C assignments of the reaction products. The 2D NMR techniques and analysis described here can be applied successfully to other synthetic reactions with the potential to produce isomeric products. PMID- 17278180 TI - Elimination of spin diffusion effects in saturation transfer experiments: application to hydrogen exchange in proteins. AB - The NMR saturation transfer experiment is widely used to characterize exchange processes in proteins that take place on the ms-s timescale. However, spin diffusion effects are inherently associated with the saturation transfer experiment and may overshadow the effect of the exchange processes of interest. As shown here, the effects from spin diffusion and exchange processes can be separated by varying the field strength of the saturation pulse, thereby allowing correct exchange rates to be obtained. The method is demonstrated using the hydrogen exchange process in the protein Escherichia coli thioredoxin as an example. PMID- 17278179 TI - Spin-spin coupling and substituent and halogen isotope shift effects in the fluorine NMR spectra of fluorinated cyclopropanes and cyclopropyl ethers. AB - The (19)F NMR spectra of a series of fluorinated cyclopropanes, most of which contain chlorine or bromine on the ring, have been observed and analyzed. A scheme has been developed to assign the resonances and the molecular stereochemistry, based on substituent effects, comparison of related molecules, and isotope shifts induced by the halogens. Replacement of fluorine by chlorine shifts cis fluorine resonances to lower field, and bromine has an even greater downfield influence. However, the shift effect of bromine compared to chlorine on gem or trans fluorines is variable. The magnitude of the isotope shifts is found to be regularly related to the geometrical relationship of the halogen to the observed fluorine and thus makes a significant contribution to the fluorine assignments. The three-bond spin-spin coupling constants between fluorine atoms in cyclopropanes display unusual behavior and are not helpful for assignment of the fluorine resonances. The signs of the coupling constants have been investigated by spin-tickling experiments, and the previously developed relation of the coupling constant sign to its temperature dependence has been found to be violated for some molecules. PMID- 17278182 TI - Re: Oral anticoagulants and the risk of osteoporotic fractures among elderly. PMID- 17278183 TI - Survey research methods in evaluation and case-control studies. AB - Survey research methods are widely used in two types of analytic studies: evaluation studies that measure the effects of interventions; and population based case-control studies that investigate the effects of various risk factors on the presence of disease. This paper provides a broad overview of some design and analysis issues related to such studies, illustrated with examples. The lack of random assignment to treatment and control groups in many evaluation studies makes controlling for confounders critically important. Confounder control can be achieved by matching in the design and by various alternative methods in the analysis. One popular analytic method of controlling for confounders is propensity scoring, which bears a close resemblance to survey weighting. The use of population-based controls has become common in case-control studies. For reasons of cost, population-based controls are often identified by telephone surveys using random digit dialling (RDD) sampling methods. However, RDD surveys are now experiencing serious problems with response rates. A recent alternative approach is to select controls from frames such as driver license lists that contain valuable demographic information for use in matching. Methods of analysis developed in the survey sampling literature are applicable, at least to some degree, in the analyses of evaluation and population-based case-control studies. In particular, the effects of complex sample designs can be taken into account using survey sampling variance estimation methods. Several survey analysis software packages are available for carrying out the computations. PMID- 17278184 TI - Combining information from multiple surveys to enhance estimation of measures of health. AB - Survey estimates are often affected by non-sampling errors due to missing data, coverage error, and measurement or response error. Such non-sampling errors can be difficult to assess, and possibly correct for, using information from a single survey. Thus, combining information from multiple surveys can be beneficial. In addition, combining information from multiple surveys can help to reduce sampling error. This article describes four examples of projects undertaken by researchers within and outside the National Center for Health Statistics of the Centers for Disease Control and Prevention, in which information from multiple surveys was combined to adjust for non-sampling errors and thereby enhance estimation of various measures of health. The four projects can be described briefly as follows: (1) combining estimates from a survey of households and a survey of nursing homes to extend coverage; (2) using information from an interview survey to bridge the transition in race reporting in the United States census; (3) combining information from an examination survey and an interview survey to improve on analyses of self-reported data; and (4) combining information from two interview surveys to enhance small-area estimation. The article highlights the goals, techniques, and results from the four projects and discusses issues that can arise when information is combined from multiple surveys. Published in 2007 by John Wiley & Sons, Ltd. PMID- 17278185 TI - Correcting for non-compliance of repeated binary outcomes in randomized clinical trials: randomized analysis approach by Yutaka Matsuyama, Statistics in Medicine 2002; 21:675-687. PMID- 17278186 TI - Determinants of participation in social support groups for prostate cancer patients. AB - OBJECTIVE: This study aims at determining factors related to the intention to participate and actual participation in social support groups for prostate cancer patients, using the framework of the theory of planned behavior. The factors studied are background variables, medical variables, psychosocial variables and attitude, social norms and perceived control. METHODS: From various sources, 238 prostate cancer patients were recruited. The patients filled out a questionnaire, containing standardized instruments on several psychosocial problems and social support, besides questions on demographic and medical characteristics. A specific questionnaire was developed to assess attitude, social norms and perceived control concerning the participation in support groups. From the recruited men, 48 participated in one of the support groups organized by the researchers. RESULTS: Logistic regression revealed that age, lack of social support, a positive attitude and a high perceive control are predictive for the intention to participate in a social support group. Perceived control and the number of prostate-specific problems did predict the factual participation. CONCLUSION: Many prostate cancer patients report psychosocial problems. A more positive attitude towards group participation and the availability of support groups at short travel distance facilitates the interest in and the factual group participation. PRACTICAL IMPLICATIONS: Urologist and urological nurses can play a role in creating a more positive attitude towards group participation, especially if the social support system is weak. Groups should be organized close to patients' place of residence. PMID- 17278188 TI - Clinical role and importance of fluorescence in situ hybridization method in diagnosis of H pylori infection and determination of clarithromycin resistance in H pylori eradication therapy. AB - H pylori is etiologically associated with gastritis, gastric and duodenal ulcers, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Eradicating H pylori may convert rapidly the outcome of related diseases with the use of more accurate diagnostic molecular tests. Indeed some of the tests cannot give the evidence of current infection; H pylori can be detected by noninvasive and invasive methods, the latter requiring an endoscopy. Eradication failure is a big problem in H pylori infection. Recently, clarithromycin resistance in H pylori strains is increasing and eradication therapy of this bacterium is becoming more difficult. Molecular methods have frequently been applied besides phenotypic methods for susceptibility testing to detect clarithromycin resistance due to mutations in the 2143 and 2144 positions of 23S rRNA gene. Fluorescence in situ hybridization (FISH) method on paraffin embedded tissue is a rapid, accurate and cost-effective method for the detection of H pylori infection and to determine clarithromycin resistance within three hours according to the gold standards as a non-culture method. This method can also be applied to fresh biopsy samples and the isolated colonies from a culture of H pylori, detecting both the culturable bacillary forms and the coccoid forms of H pylori, besides the paraffin embedded tissue sections. This technique is helpful for determining the bacterial density and the results of treatment where clarithromycin has been widely used in populations to increase the efficacy of the treatment and to clarify the treatment failure in vitro. PMID- 17278189 TI - Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis. AB - AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expressions in the development and progression of reflux esophagitis-Barrett's metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin embedded tissue samples by immunohistochemistry including patients with reflux esophagitis (n = 7), Barrett's metaplasia (n = 14), Barrett and esophagitis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant. RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett's metaplasia and the other groups. No major changes were observed between Barrett, esophagitis, and Barrett and concomitant esophagitis. Barrett and concomitant dysplasia, and adenocarcinoma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = -0.82). CONCLUSION: Decreased GST and increased expression of MMP-9 in Barrett's metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dysplasia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett's esophagus might be useful to identify patients at higher risk for progression to cancer. PMID- 17278190 TI - p53-expressing conditionally replicative adenovirus CNHK500-p53 against hepatocellular carcinoma in vitro. AB - AIM: To develop a conditionally replicative gene-viral vector system called CNHK500-p53, which contains dual promoters within the E1 region, and combines the advantages of oncolytic virus and gene therapies for hepatocellular carcinoma (HCC). METHODS: CNHK500-p53 was constructed by using human telomerase reverse transcriptase (hTERT) promoter to drive adenovirus E1a gene and hypoxia response element (HRE) promoter to drive adenovirus E1b gene. p53 gene expressing cassette was inserted into the genome of replicative virus. Viral replication experiments, cytopathic effect (CPE) and methyl thiazolyl tetrazolium (MTT) assay were performed to test the selective replication and oncolytic efficacy of CNHK500 p53. RESULTS: Immunohistochemistry verified that infection with CNHK500-p53 was associated with selective replication of adenovirus and production of p53 protein in telomerase-positive and hypoxia-inducible factor-dependent HCC cells. p53 protein secreted from HepG2, infected with CNHK500-p53 was significantly higher than that infected with nonreplicative adenovirus Ad-p53 in vitro (388 +/- 34.6 microg/L vs 76.3 +/- 13.17 microg/L). Viral replication experiments showed that replication of CNHK500-p53 and CNHK500 or WtAd5, was much stronger than that of Ad-p53 in tested HCC cell lines. CPE and MTT assay indicated that CNHK500-p53 selectively replicated in and killed HCC cells while leaving normal cells unaffected. CONCLUSION: A more efficient gene-viral system is developed by combining selective oncolysis with exogenous expression of p53 against HCC cells. PMID- 17278192 TI - Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray. AB - AIM: To explore the molecular events taking place during human colon cancer development and progression through high-throughput tissue microarray analysis. METHODS: We constructed two separate tissue microarrays containing 1.0 mm or 1.5 mm cylindrical samples acquired from 112 formalin-fixed and paraffin-embedded blocks, including carcinomas (n = 85), adenomatous polyps (n = 18), as well as normal para-cancerous colon tissues (n = 9). Immunohistochemical staining was applied to the analysis of the consecutive tissue microarray sections with antibodies for 11 different proteins, including p53, p21, bcl-2, bax, cyclin D1, PTEN, p-Akt1, beta-catenin, c-myc, nm23-h1 and Cox-2. RESULTS: The protein expressions of p53, bcl-2, bax, cyclin D1, beta-catenin, c-myc, Cox-2 and nm23-h1 varied significantly among tissues from cancer, adenomatous polyps and normal colon mucosa (P = 0.003, P = 0.001, P = 0.000, P = 0.000, P = 0.034, P = 0.003, P = 0.002, and P = 0.007, respectively). Chi-square analysis showed that the statistically significant variables were p53, p21, bax, beta-catenin, c-myc, PTEN, p-Akt1, Cox-2 and nm23-h1 for histological grade (P = 0.005, P = 0.013, P = 0.044, P = 0.000, P = 0.000, P = 0.029, P = 0.000, P = 0.008, and P = 0.000, respectively), beta-catenin, c-myc and p-Akt1 for lymph node metastasis (P = 0.011, P = 0.005, and P = 0.032, respectively), beta-catenin, c-myc, Cox-2 and nm23-h1 for distance metastasis (P = 0.020, P = 0.000, P = 0.026, and P = 0.008, respectively), and cyclin D1, beta-catenin, c-myc, Cox-2 and nm23-h1 for clinical stages (P = 0.038, P = 0.008, P = 0.000, P = 0.016, and P = 0.014, respectively). CONCLUSION: Tissue microarray immunohistochemical staining enables high throughput analysis of genetic alterations contributing to human colon cancer development and progression. Our results implicate the potential roles of p53, cyclin D1, bcl-2, bax, Cox-2, beta-catenin and c-myc in development of human colon cancer and that of bcl-2, nm23-h1, PTEN and p-Akt1 in progression of human colon cancer. PMID- 17278191 TI - Early apoptosis and cell death induced by ATX-S10Na (II)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells. AB - AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (II). METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting. RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-x(L), were decreased in Bax- and p53-independent manner. CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na (II) are mediated by p53-Bax network and low levels of Bcl-2 and Bcl-x(L) proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy. PMID- 17278193 TI - Neural mechanism of acupuncture-modulated gastric motility. AB - AIM: To investigate the acupuncture-modulated gastric motility and its underlying neural mechanism. METHODS: Intragastric pressure and/or waves of gastric contraction in rats were recorded by intrapyloric balloon and changes of gastric motility induced by acupuncture stimulation were compared with the background activity before any stimulation. Gastro-vagal or splanchnic-sympathetic nerves were recorded or cut respectively for investigating the involvement of autonomic nerve pathways. Spinalization experiment was also performed. RESULTS: Acupuncture stimulation by exciting A delta and/or C afferent fibers, could only modulate gastric motility. Acupuncture-stimulation on fore- and hind-limbs evoked a moderate gastric motility followed by increased vagus discharges with unchanged sympathetic activity, while the same stimulus to the acupoints in abdomen resulted in reversed effects on gastric motility and autonomic nervous activities. The inhibitory gastric response was completely abolished by splanchnic denervation, but the facilitative gastric response to stimulation of acupoints in limbs was not influenced, which was opposite to the effect when vagotomy was performed. The similar depressive effects were produced by the stimulation at the acupoints homo-segmental to the gastric innervation in the animals with or without spinalization. However, the facilitation induced by the stimulation at the acupoints hetero-segmental to the gastric innervation was not observed in the spinalized animals. CONCLUSION: Facilitative effects of stimulating hetero-segmental acupoints are involved in the intact preparation of vagal nerves and spinal cord, while the inhibitory response induced by stimulating homo-segmental acupoints is involved in the intact preparation of sympathetic nerves. Only the acupuncture-stimulation with intensity over the threshold of A delta and/or C afferent fibers can markedly modulate gastrointestinal motility. PMID- 17278187 TI - Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation. AB - Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords "liver", "ischaemic reperfusion", "ischaemic preconditioning", "regeneration", "hepatectomy" and "transplantation". The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growth-promoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation. PMID- 17278194 TI - Experimental study of therapeutic efficacy of Baicalin in rats with severe acute pancreatitis. AB - AIM: To observe the therapeutic efficacy of Baicalin in rats with severe acute pancreatitis (SAP) and explore its therapeutic mechanisms. METHODS: The SAP rat models were randomly divided into the model control group, Baicalin treatment group, octreotide treatment group and sham operation group. All groups were randomly subdivided into 3 h, 6 h and 12 h groups with 15 rats in each group. The survival, ascites volume and pathological changes of pancreas in all rats were observed at different time points after operation. The plasma amylase content and serum TNF-alpha, IL-6, malonaldehyde (MDA) and PLA(2) contents were also determined. RESULTS: The survival was not obviously different between the treated groups, and was significantly higher in treated groups at 12 h compared to the model control group (P < 0.05, 15 vs 10). The ascites/body weight ratio at 3 h and 6 h was significantly lower in Baicalin treatment group compared to the model control group and octreotide treatment group (P < 0.05, 1.00 vs 2.02 and 1.43 and P < 0.001, 2.29 (1.21) vs 2.70 (0.80) and 2.08 (2.21), respectively). The contents of amylase, TNF-alpha, IL-6, MDA and PLA(2) were significantly lower in the treated groups than in the model control group (P < 0.05, 4342 vs 5303, 5058 vs 6272 in amylase, P < 0.01, 21.90 vs 36.30, 23.80 vs 39.70, 36 vs 54.35 in MDA and 56.25 vs 76.10 in PlA(2), or P < 0.001, 65.10 and 47.60 vs 92.15 in TNF alpha, 3.03 vs 5.44, 2.88 vs 6.82, 2.83 vs 5.36 in IL-6, respectively). The pathological scores of pancreas in the treated groups were significantly lower than that in the model control group (P < 0.05, 9.00 vs 10.05, 6.00 vs 9.00, 8.00 vs 10.05), but no marked difference was found between the treated groups. CONCLUSION: The Baicalin injection has significant therapeutic effects on SAP rats, its effects are similar to those of octreotide. The Baicalin injection is also cheap and has a big application range, quite hopefully to be used in clinical treatment of SAP. PMID- 17278195 TI - Antidiabetic effects of chitooligosaccharides on pancreatic islet cells in streptozotocin-induced diabetic rats. AB - AIM: To investigate the effect of chitooligosaccharides on proliferation of pancreatic islet cells, release of insulin and 2 h plasma glucose in streptozotocin-induced diabetic rats. METHODS: In vitro, the effect of chitooligosaccharides on proliferation of pancreatic islet cells and release of insulin was detected with optical microscopy, colorimetric assay, and radioimmunoassay respectively. In vivo, the general clinical symptoms, 2 h plasma glucose, urine glucose, oral glucose tolerance were examined after sixty days of feeding study to determine the effect of chitooligosaccharides in streptozotocin induced diabetic rats. RESULTS: Chitooligosaccharides could effectively accelerate the proliferation of pancreatic islet cells. Chitooligosaccharides (100 mg/L) had direct and prominent effect on pancreastic beta cells and insulin release from islet cells. All concentrations of chitooligosaccharides could improve the general clinical symptoms of diabetic rats, decrease the 2 h plasma glucose and urine glucose, and normalize the disorders of glucose tolerance. CONCLUSION: Chitooligosaccharides possess various biological activities and can be used in the treatment of diabetes mellitus. PMID- 17278196 TI - A randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation. AB - AIM: To evaluate the efficacy and safety of tegaserod, 6 mg twice daily (b.i.d.), in men and women with chronic constipation (CC) from China. METHODS: This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatment free baseline period, patients were randomized to receive either tegaserod (6 mg b.i.d.) or placebo (b.i.d.) for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements (CSBMs) during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients' daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events (AEs). RESULTS: A total of 607 patients were randomized to receive either tegaserod (n = 304) or placebo (n = 303). Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo (1.39 vs 0.91, P = 0.0002). A statistically significant difference in favor of tegaserod was also observed for a mean increase > or = 1 CSBM/wk over wk 1-4 (47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018) and for the absolute number of > or = 3 CSBMs/wk over wk 1-4 (25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021). Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod (3.6%) compared with placebo (1.7%). CONCLUSION: Tegaserod treatment improved multiple symptoms of CC and was associated with a favorable safety profile. PMID- 17278197 TI - Influence of age on outcome of total laparoscopic fundoplication for gastroesophageal reflux disease. AB - AIM: To demonstrate that age does not influence the choice of treatment for gastroesophageal reflux disease (GERD). We hypothesized that the outcome of total fundoplication in patients > 65 years is similar to that of patients aged < or = 65 years. METHODS: Four hundred and twenty consecutive patients underwent total laparoscopic fundoplication for GERD. Three hundred and fifty-five patients were younger than 65 years (group Y), and 65 patients were 65 years or older (group E). The following elements were considered: presence, duration, and severity of GERD symptoms; presence of a hiatal hernia; manometric evaluation, 24 h pH monitoring data, duration of operation; incidence of complications; and length of hospital stay. RESULTS: Elderly patients more often had atypical symptoms of GERD and at manometric evaluation had a higher rate of impaired esophageal peristalsis in comparison with younger patients. A mild intensity of heartburn often leads physicians to underestimate the severity of erosive esophagitis. The duration of the operation was similar between the two groups. The incidence of intraoperative and postoperative complications was low and the difference was not statistically significant between the two groups. An excellent outcome was observed in 92.9% young patients and 91.9% elderly patients. CONCLUSION: Laparoscopic antireflux surgery is a safe and effective treatment for GERD even in elderly patients, warranting low morbidity and mortality rates and a significant improvement of symptoms comparable to younger patients. PMID- 17278199 TI - Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan. AB - AIM: To investigate active cytomegalovirus (CMV) infection following the cyclosporine A (CyA) treatment of steroid-refractory ulcerative colitis (UC). METHODS: Twenty-three patients with severe UC not responding to steroid therapy (male 14, and female 9) enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA (average 4 mg/kg per day) for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology (IgM antibody by ELISA), quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin (HE)-stained colonic biopsies. CMV infection was indicated by positive results in any test. RESULTS: No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV (IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%). There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection (83.3%) required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION: Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immuno suppressive therapy. PMID- 17278198 TI - Chios mastic treatment of patients with active Crohn's disease. AB - AIM: To evaluate the effectiveness of mastic administration on the clinical course and plasma inflammatory mediators of patients with active Crohn's disease (CD). METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Activity Index (CDAI), Nutritional Risk Index (NRI), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values +/- SE and P < 0.05 was considered to indicate statistical significance. RESULTS: Patients exhibited significant reduction of CDAI (222.9 +/- 18.7 vs 136.3 +/- 12.3, P = 0.05) as compared to pretreament values. Plasma IL-6 was significantly decreased (21.2 +/- 9.3 pg/mL vs 7.2 +/- 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 +/- 13.1 mg/mL vs 19.7 +/ 5.5, P = 0.028). TAP was significantly increased (0.15 +/- 0.09 vs 0.57 +/- 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION: The results suggest that mastic significantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately active CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD. PMID- 17278200 TI - Patients without hepatocellular carcinoma progression after transarterial chemoembolization benefit from liver transplantation. AB - AIM: To assess the outcome of patients, who underwent transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) and subsequently liver transplantation (OLT) irrespective of tumor size when no tumor progression was observed. METHODS: Records, imaging studies and pathology of 84 patients with HCC were reviewed. Ten patients were not treated at all, 67 patients had TACE and 35 of them were listed for OLT. Tumor progression was monitored by ultrasound and AFP level every 6 wk. Fifteen patients showed signs of tumor progression without transplantation. The remaining 20 patients underwent OLT. Further records of 7 patients with HCC seen in histological examination after OLT were included. RESULTS: The patients after TACE without tumor progression underwent transplantation and had a median survival of 92.3 mo. Patients, who did not qualify for liver transplantation or had signs of tumor progression had a median survival of 8.4 mo. The patients without treatment had a median survival of 3.8 mo. Independent of International Union Against Cancer (UICC) stages, the patients without tumor progression and subsequent OLT had longer median survival. No significant difference was seen in the OLT treated patients if they did not fulfill the Milan criteria. CONCLUSION: Selection of patients for OLT based on tumor progression results in good survival. The evaluation of HCC patients should not only be based on tumor size and number of foci but also on tumor progression and growth behavior under therapy. PMID- 17278202 TI - High-altitude gastrointestinal bleeding: an observation in Qinghai-Tibetan railroad construction workers on Mountain Tanggula. AB - AIM: To investigate the gastrointestinal bleeding (GIB) in people from lowland to high altitude and in workers on Mountain Tanggula and its causes as well as treatment and prophylaxis. METHODS: From 2001 to October 2003, we studied GIB in 13502 workers constructing the railroad on Mountain Tanggula which is 4905 m above the sea level. The incidence of GIB in workers at different altitudes was recorded. Endoscopy was performed when the workers evacuated to Golmud (2808 m) and Xining (2261 m). The available data on altitude GIB were analyzed. RESULTS: The overall incidence of GIB was 0.49% in 13502 workers. The incidence increased with increasing altitude. The onset of symptoms in most patients was within three weeks after arrival at high altitude. Bleeding manifested as hematemesis, melaena or hematochezia, and might be occult. Endoscopic examination showed that the causes of altitude GIB included hemorrhage gastritis, gastric ulcer, duodenal ulcer, and gastric erosion. Experimental studies suggested that acute gastric mucosal lesion (AGML) could be induced by hypoxic and cold stress, which might be the pathogenesis of altitude GIB. Those who consumed large amount of alcohol, aspirin or dexamethasone were at a higher risk of developing GIB. Persons who previously suffered from peptic ulcer or high-altitude polycythemia were also at risk of developing GIB. Early diagnosis, evacuation, and treatment led to early recovery. CONCLUSION: GIB is a potentially life threatening disease, if it is not treated promptly and effectively. Early diagnosis, treatment and evacuation lead to an early recovery. Death due to altitude GIB can be avoided if early symptoms and signs are recognized. PMID- 17278201 TI - Esophageal mesenchymal tumors: endoscopy, pathology and immunohistochemistry. AB - AIM: To study the endoscopic, pathological and immunohistochemical features of esophageal mesenchymal tumors. METHODS: Twenty-nine patients diagnosed as esophageal mesenchymal tumors by electronic endoscopy and endoscopic ultrasound (EUS) were observed under light microscopes, and all tissues were stained by the immunohistochemical method. The expression of CD117, CD34, SMA and desmin were measured by staining intensity of cells and positive cell ratios. RESULTS: Endoscopically, esophageal gastrointestinal stromal tumors (GISTs) and leiomyomas (LMs) had similar appearances, showing submucosal protuberant lesions. They all showed low echo images originated from the muscularis propria or muscularis mucosa on EUS. Endoscopy and EUS could not exactly differentiate esophageal GISTs from LMs. Microscopically, there were two kinds of cells: spindle cell type and epitheloid cell type in esophageal GISTs. Leiomyomas and leiomyosarcomas were only of spindle cell type. One malignancy was found in five cases of esophageal GISTs, and one malignancy in 24 cases of leiomyomas and leiomyosarcomas. Using Fisheros exact method, the differences of malignant lesion proportion were not significant between esophageal LMs and GISTs, 1/5 vs 1/24 (P > 0.05). All cases of esophageal GISTs were positive for CD117, and 3 cases were also positive for CD34. The 24 cases of leiomyomas and leiomyosarcomas were all negative for CD117 and CD34. The differences of positive rates of CD117 and CD34 were significant between esophageal GISTs and LMs, 5/5 vs 0/24, 3/5 vs 0/24 (P < 0.005). All leiomyomas and leiomyosarcomas were positive for SMA, and desmin. Among 5 cases of esophageal GISTs, 2 cases were SMA positive, and 1 case was desmin positive. The differences in positive rates and expression intensity of SMA and desmin were significant between esophageal LMs and GISTs, 24/24 vs 2/5, 24/24 vs 1/5 (P < 0.005). CONCLUSION: The most common esophageal mesenchymal tumors are leiomyomas, and esophageal GISTs are less common. Most of esophageal LMs and GISTs are benign. Endoscopy and EUS are the effective methods to diagnose esophageal mesenchymal tumors and they can provide useful information for the treatment of these tumors. However, they cannot exactly differentiate esophageal GISTs from LMs. Pathological, especially immunohistochemical features are useful to differentiate GISTs from leiomyomas. PMID- 17278203 TI - Differences in characteristics of patients with and without known risk factors for hepatocellular carcinoma in the United States. AB - AIM: To examine the clinical characteristics of a subgroup of patients with hepatocellular carcinoma (HCC) and compare them to those with known risk factors. METHODS: We used the HCC database of 306 patients seen at our institution from January 1, 1995 to December 31, 2001. Of the 306 patients, 63 (20%, group 1) had no known risk factors (hepatitis C virus, hepatitis B virus, alcohol, hemochromatosis or cirrhosis from any cause) and 243 (group 2) had one or more risk factors. RESULTS: The median age was similar in both groups, but there were disproportionate numbers of younger (< 30 years old), older (> 80 years) patients, women (33% vs 18%), and Caucasians (81% vs 52%) in group 1 as compared to group 2. There were fewer Asians (2% vs 11%) and African Americans (13% vs 27%) in group 1. Abdominal pain (70% vs 37%) was more common while gastrointestinal bleeding (0% vs 11%) and ascites (4% vs 17%) were less common in group 1 compared to group 2. Group 1 had larger tumor burden (median size 9.4 cm vs 5.7 cm) at the time of presentation, but there were no differences in the site (right, left or bilateral lesions), or number of tumors between the two groups. CONCLUSION: HCC patients without identifiable risk factors have different characteristics and clinical presentation compared to those with known risk factors. Absence of cirrhosis and larger tumor burden may explain the differences in the presenting symptoms. PMID- 17278204 TI - Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases. AB - AIM: To investigate the association between serum insulin-like growth factor 1 (IGF-1), osteocalcin, and parathyroid hormone (PTH) levels with the etiology and clinical condition of patients with chronic liver disease. METHODS: Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection: bilharziasis (9 patients), hepatitis B virus (HBV, 12 patients) and hepatitis C virus (HCV, 29 patients). The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control group. HBsAg, HBcAbIgM, HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction (RT-PCR). Anti-bilharzial antibodies were detected by indirect haem- agglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted. RESULTS: Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin (14.7 +/- 0.54 vs 3.6 +/- 0.10, P < 0.05), while that for PTH was positively correlated with total protein (70.1 +/- 2.17 vs 6.7 +/- 0.10, P < 0.05) in patients with HCV infection. CONCLUSION: Low serum IGF 1 level seems to play a critical role in the bone loss in patients with chronic liver disease. Elevated biochemical markers of bone remodeling suggest high turnover in patients with viral infection and reflect severity of the clinical stage. PMID- 17278205 TI - Per rectal portal scintigraphy as a useful tool for predicting esophageal variceal bleeding in cirrhotic patients. AB - AIM: To investigate potential roles of per rectal portal scintigraphy in diagnosis of esophageal varices and predicting the risk of bleeding. METHODS: Fifteen normal subjects and fifty cirrhotic patients with endoscopically confirmed esophageal varices were included. Patients were categorized into bleeder and non-bleeder groups according to history of variceal bleeding. All had completed per rectal portal scintigraphy using (99m)Technetium pertechnetate. The shunt index was calculated from the ratio of (99m)Technetium pertechnetate in the heart and the liver. Data were analyzed using Student's t-test and receiver operating characteristics. RESULTS: Cirrhotic patients showed a higher shunt index than normal subjects (63.80 +/- 25.21 vs 13.54 +/- 6.46, P < 0.01). Patients with variceal bleeding showed a higher shunt index than those without bleeding (78.45 +/- 9.40 vs 49.35 +/- 27.72, P < 0.01). A shunt index of over 20% indicated the presence of varices and that of over 60% indicated the risk of variceal bleeding. CONCLUSION: In cirrhotic patients, per rectal portal scintigraphy is a clinically useful test for identifying esophageal varices and risk of variceal bleeding. PMID- 17278206 TI - Increased plasma malondialdehyde and fructosamine in anemic H pylori infected patients: effect of treatment. AB - AIM: To unravel the possible association of malondialdehyde (MDA) and fructosamine in anemic H pylori infected patients and to observe the alteration in MDA and fructosamine levels in these patients after treatment for one month. METHODS: Fructosamine, MDA and glucose were estimated in 22 anemic H pylori infected patients and 16 healthy controls. Hematological parameters were also evaluated in both the groups using Sysmex-K-100 automated cell counter. The H pylori infected patients were randomly divided into two groups. H pylori infected patients in Group I received both iron supplementation and anti-H pylori therapy, while patients in Group II received only iron supplementation. All the biochemical and hematological parameters were estimated after one month of treatment. RESULTS: In anemic H pylori infected patients, while MDA (5.41 +/- 2.16 vs 2.26 +/- 0.50; P < 0.05) and fructosamine (2.64 +/- 0.93 vs 1.60 +/- 0.35; P < 0.05) were significantly increased, iron (32.72 +/- 14.93 vs 110.25 +/- 26.58; P < 0.05), hemoglobin (6.9 +/- 2.6 vs 12.66 +/- 0.74; P < 0.05) and ferritin (28.82 +/- 16.27 vs 140.43 +/- 30.72; P < 0.05) levels were significantly decreased compared with the controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with MDA. In Group I, while MDA level decreased significantly (3.11 +/- 1.73 vs 5.50 +/- 2.46; P < 0.05), there was a significant increase in iron (84.09 +/- 29.51 vs 36.09 +/- 17.81; P < 0.05), hemoglobin (10.40 +/- 1.11 vs 7.42 +/- 1.90; P < 0.05) and ferritin (116.91 +/- 63.34 vs 30.46 +/- 17.81; P < 0.05) levels after one month. There was no significant change in the levels of fructosamine in group I after treatment. Similarly, no significant alterations were noted in the levels of MDA, fructosamine, hemoglobin or ferritin in Group II patients after one month of treatment. CONCLUSION: An increased level of fructosamine and MDA was found in anemic H pylori infected patients. Present data supports the premise that lipid peroxides per se do play a role in the glycation of plasma proteins. Furthermore, the findings from this study indicate that treatment for both anemia and H pylori infections is required for lowering the levels of lipid peroxides in these patients. PMID- 17278207 TI - Esophagotracheal fistula caused by gastroesophageal reflux 9 years after esophagectomy. AB - Fistula between digestive tract and airway is one of the complications after esophagectomy with lymph node dissection. A case of esophagotracheal fistula secondary to esophagitis 9 years after esophagectomy and gastric pull-up for treatment of esophageal carcinoma is described. It was successfully treated with transposition of a pedicled pectoralis major muscle flap. PMID- 17278208 TI - A case of biliary gastric fistula following percutaneous radiofrequency thermal ablation of hepatocellular carcinoma. AB - Percutaneous radiofrequency thermal ablation (RFA) is an effective and safe therapeutic modality in the management of liver malignancies, performed with ultrasound guidance. Potential complications of RFA include liver abscess, ascites, pleural effusion, skin burn, hypoxemia, pneumothorax, subcapsular hematoma, hemoperitoneum, liver failure, tumour seeding, biliary lesions. Here we describe for the first time a case of biliary gastric fistula occurred in a 66 year old man with a Child's class A alcoholic liver cirrhosis as a complication of RFA of a large hepatocellular carcinoma lesion in the III segment. In the light of this case, RFA with injection of saline between the liver and adjacent gastrointestinal tract, as well as laparoscopic RFA, ethanol injection (PEI), or other techniques such as chemoembolization, appear to be more indicated than percutaneous RFA for large lesions close to the gastrointestinal tract. PMID- 17278209 TI - Spontaneous rupture of a hepatic hydatid cyst into the peritoneum causing only mild abdominal pain: a case report. AB - Hydatid disease is an endemic disease in certain areas of the world. It is located mostly in the liver. Spontaneous rupture of the hydatid cyst into the peritoneum is a rare condition, which is accompanied by serious morbidity and mortality generally. We present herein a case with a spontaneous rupture of a hepatic hidatid disease into the peritoneum without any serious symptoms. A 15 year-old boy was admitted to the emergency room with a mild abdominal pain lasting for a day. Physical examination revealed only mild abdominal tenderness. There was no history of trauma or complaints related to hydatid diseases. Ultrasonography showed a large amount of free fluid and a cystic lesion with irregular borders in the liver. He was operated on. Postoperative albendazol therapy was given for 2 mo. No recurrence or secondary hydatidosis was seen on CT investigation in the 3rd, 6th and 12th mo following surgery. PMID- 17278210 TI - Carcinosarcoma of the liver with mesenchymal differentiation. AB - We report an extremely rare case where a mesenchymal differentiation, especially embryonal sarcoma, was demonstrated in cholangiocarcinoma. At autopsy, a yellowish-white tumor (15 cm x 12 cm) was found in the right hepatic lobe, and there were several daughter nodules in both hepatic lobes. Histologically, most of the main tumor and all of the daughter nodules examined showed sarcomatous changes (spindle cells, pleomorphic cells and hyalization). Histologic examination of a part of the main tumor disclosed a focus of adenocarcinoma within the tumor. The frequent transitions between the adenocarcinomatous areas and the sarcomatous areas suggested that sarcomatous transformation occurred in the cholangiocarcinoma and then spread rapidly. Immunohistochemically, the adenocarcinomatous elements were positive for cytokeratin, carcinoembryonic antigen (CEA) and epithelial membrane antigen, and negative in the sarcomatous cells. Vimentin was positive only in the sarcomatous elements. The findings of the present case support the view that carcinosarcomas represent carcinomas that develop sarcomatous elements via metaplasia of the epithelial element. PMID- 17278211 TI - Metastatic melanoma to the common bile duct causing obstructive jaundice: a case report. AB - Metastatic melanoma to the common bile duct is very rare with only 18 cases reported so far. We report a 46 year old women who, 18 mo after excision of a skin melanoma, developed a painless progressive obstructive jaundice. At operation a melanoma within the distal third of the common bile duct was found. There were no other secondaries within the abdomen. The common bile duct, including the tumor, was resected and anastomosed with Roux-en-Y jejunal limb. The patient survived 31 mo without any sign of local recurrence and was submitted to three other operations for axillar and brain secondaries, from which she finally died. Radical resection of metastatic melanoma to the common bile duct may result in lifelong relief of obstructive jaundice. It is safe and relatively easy to perform. In other cases, a less aggressive approach, stenting or bypass procedures, should be adopted. PMID- 17278212 TI - Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion. AB - Gastric acid plays an important role in digesting food (especially protein), iron absorption, and destroying swallowed micro-organisms. H+ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms. Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like (ECL) cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, long-term hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastrin levels, leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concern, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and clinically in the regulation of gastric acid secretion. PMID- 17278213 TI - Impact of tiny miRNAs on cancers. AB - miRNAs are a class of small, approximately 22nt, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They play profound and pervasive roles in manipulating gene expression involved in cell development, proliferation and apoptosis in various eukaryotes, which, in theory, could provide an access to many human diseases in theory. Recent evidence demonstrates that aberrant miRNA expression is a hallmark of tumor development, revealing that miRNA genes could function as potential oncogenes and repressors in the human body. miRNAs can affect tumorigenesis mainly by interrupting the cell cycle at the cellular level and by interacting with signaling, oncogenes and with the response to environmental factors at the molecular level. The established miRNA expression signature could be a potent tool to diagnose and treat human cancers in the future. PMID- 17278214 TI - Chromosome 11 aneusomy in esophageal cancers and precancerous lesions--an early event in neoplastic transformation: an interphase fluorescence in situ hybridization study from south India. AB - AIM: To detect aneusomic changes with respect to chromosome 11 copy number in esophageal precancers and cancers wherein the generation of cancer-specific phenotypes is believed to be associated with specific chromosomal aneuploidies. METHODS: We performed fluorescence in situ hybridization (FISH) on esophageal tissue paraffin sections to analyze changes in chromosome 11 copy number using apotome-generated images by optical sectioning microscopy. Sections were prepared from esophageal tumor tissue, tissues showing preneoplastic changes and histologically normal tissues (control) obtained from patients referred to the clinic for endoscopic evaluation. RESULTS: Our results demonstrated that aneusomy was seen in all the cancers and preneoplastic tissues, while none of the controls showed aneusomic cells. There was no increase in aneusomy from precancers to cancers. CONCLUSION: Our results suggest that evaluation of chromosome 11 aneusomy in esophageal tissue using FISH with an appropriate signal capture analysis system, can be used as an ancillary molecular marker predictive of early neoplastic changes. Future studies can be directed towards the genes on chromosome 11, which may play a role in the neoplastic transformation of esophageal precancerous lesions to cancers. PMID- 17278215 TI - Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo. AB - AIM: To investigate the effects of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3 yl) propionic acid (NM-3) alone and in combination with carboplatin on tumor growth and apoptosis in mouse models of human gastric cancer constructed by subcutaneous implantation of histologically intact tumor tissue. METHODS: Human gastric cancer SGC-7901 tissues were implanted into the dorsal subcutis of nude mice. One week after tumors reached to a volume of 50-100 mm(3) for around 1 wk, these mice were randomly divided into 8 groups (n = 10). NM-3 was injected peritoneally at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg every other day for 5 wk, combined with carboplatin (5 mg/kg) every third day for 4 wk. As controls of combined treatment, another 4 groups of mice were injected with either NM-3 at 10 mg/kg, 20 mg/kg or 40 mg/kg, or with carboplatin alone (5 mg/kg). The control mice received normal saline. Tumor weight, tumor growth inhibition (TGI), and intratumoral microvessel density (MVD) were evaluated. Apoptosis of human gastric cancer was detected by TUNEL method and flow cytometry analysis, respectively. RESULTS: The mean tumor volume (692.40 +/- 58.43 mm(3), 548.30 +/- 66.02 mm(3), 382.13 +/- 43.52 mm(3)) after treatment with carboplatin combined NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg was lower than that after treatment with either NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg or with carboplatin alone. Compared with the normal saline group, NM-3 administered at 10 mg/kg, 20 mg/kg or 40 mg/kg significantly reduced the tumor weight in these groups (P < 0.05). Carboplatin used alone at 5 mg/kg showed minimal effects. But NM-3 in combination with carboplatin had greater effects of tumor weight than either NM-3 or carboplatin alone. NM-3 alone at the dose 10 mg/kg or in combination with carboplatin had no obvious effects on body changes. Two mice died of diarrhea in each of the two groups treated with 40 mg/kg NM-3 or with 40 mg/kg NM-3 in combination with carboplatin. A significant increase in apoptosis was observed in the NM-3 treated groups, and the effect was more significant in the groups treated with carboplatin in combination with NM-3 at 10 mg/kg, 20 mg/kg and 40 mg/kg, than in the control group. The induction of apoptosis was positively associated with the dose of NM-3. NM-3 significantly reduced the neo microvascular formation of gastric cancer. The MVD was lower in the groups treated with NM-3 or with NM-3 in combination with carboplatin than in the group treated with carboplatin or in the normal saline group (P < 0.05). CONCLUSION: The results suggest that the inhibitory effect of NM-3 on gastric cancer growth is mediated through decreased angiogenesis and the increased induction of apoptosis. Furthermore, NM-3 alone at the dose of 10 mg/kg or in combination with carboplatin has no obvious effects on body changes, indicating that NM-3 in combination with carboplatin may be effective in the treatment of gastric cancer. The toxicity of NM-3 needs further studies. PMID- 17278216 TI - Usefulness of two independent histopathological classifications of tumor regression in patients with rectal cancer submitted to hyperfractionated pre operative radiotherapy. AB - AIM: To assess the usefulness of two independent histopathological classifications of rectal cancer regression following neo-adjuvant therapy. METHODS: Forty patients at the initial stage cT3NxM0 submitted to preoperative radiotherapy (42 Gy during 18 d) and then to radical surgical treatment. The relationship between "T-downstaging" versus regressive changes expressed by tumor regression grade (TRG 1-5) and Nasierowska-Guttmejer classification (NG 1-3) was studied as well as the relationship between TRG and NG versus local tumor stage ypT and lymph nodes status, ypN. RESULTS: Complete regression (ypT0, TRG 1) was found in one patient. "T-downstaging" was observed in 11 (27.5%) patients. There was a weak statistical significance of the relationship between "T-downstaging" and TRG staging and NG stage. Patients with ypT1 were diagnosed as TRG 2-3 while those with ypT3 as TRG5. No lymph node metastases were found in patients with TRG 1-2. None of the patients without lymph node metastases were diagnosed as TRG 5. Patients in the ypT1 stage were NG 1-2. No lymph node metastases were found in NG 1. There was a significant correlation between TRG and NG. CONCLUSION: Histopathological classifications may be useful in the monitoring of the effects of hyperfractionated preoperative radiotherapy in patients with rectal cancer at the stage of cT3NxM0. There is no unequivocal relationship between "T downstaging" and TRG and NG. There is some concordance in the assessment of lymph node status with ypT, TRG and NG. TRG and NG are of limited value for the risk assessment of the lymph node involvement. PMID- 17278217 TI - Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B. AB - AIM: To assess the performance of several non-invasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis (F > or = 2 by METAVIR) and cirrhosis (F4 by METAVIR) in chronic hepatitis B (CHB). METHODS: One hundred and ten consecutive patients (80 males, 30 females, mean age: 42.6 +/- 11.3) with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio (APRI), Fornso index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index (GUCI), Hui's model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive (PPV) and negative (NPV) predictive values, accuracy and area under the curve (AUC). RESULTS: PPV for significant fibrosis was excellent (100%) with Forns and high (> 92%) with APRI, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker (NPV < 65%). Fibrotest had the best PPV and NPV for cirrhosis (87% and 90%, respectively). Fibrotest showed the best AUC for both significant fibrosis and cirrhosis (0.85 and 0.76, respectively). Stepwise combination algorithms of APRI, Fibrotest and biopsy showed excellent performance (0.96 AUC, 100% NPV) for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION: In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis. PMID- 17278218 TI - Serum-free culture of H pylori intensifies cytotoxicity. AB - AIM: To perform a long culture passage of H pylori without serum, taking into account its cytotoxicity and the presence of the probable new cytotoxic factor. METHODS: One sample of H pylori 60190 (ATCC 49503) was grown on Brain Heart Infusion (BHI) agar containing 0.5% 2,6-di-O-methyl-beta-cyclodextrin without any serum, being passaged 70-100 times every 3-4 d for approximately 2 h, while another sample of H pylori contained 70 mL/L fetal calf serum without 2,6-di-O methyl-beta-cyclodextrin. Their supernatant and extract after 16 h in culture were evaluated for changes in cell morphology and for cell viability using HeLa cells. Furthermore, the characteristics of the probable cytotoxic factor in the extract were examined on partial purification studies and its cytotoxicity was evaluated in various human cells. RESULTS: The supernatant and the extract of the bacterium grown on serum-free medium had strong cytotoxicity compared with those grown on serum-containing medium. They irreversibly damaged HeLa cells without vacuolation that was altogether different from that of the bacterium when grown with serum. Their cytotoxicity was easily measured by cell viability assay. The probable cytotoxic factor partially purified and detected by chromatography had characteristics difference from that of vacuolating toxin and a broad cytotoxicity toward various cell lines. CONCLUSION: Serum-free long culture method of H pylori makes its supernatant and its extract cytotoxic enough to be easily measured by cell viability assay. The probable cytotoxic factor has a unique characteristic and might be a new cytotoxin. PMID- 17278219 TI - Pretreatment with adenosine and adenosine A1 receptor agonist protects against intestinal ischemia-reperfusion injury in rat. AB - AIM: To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury. METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N(6)-cyclopentyladenosine, A1 receptor agonist or 8-cyclopentyl-1,3-dipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase, malondialdehyde, and reduced glutathione levels were measured. RESULTS: Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist. CONCLUSION: The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content. PMID- 17278220 TI - Influence of dexamethasone on inflammatory mediators and NF-kappaB expression in multiple organs of rats with severe acute pancreatitis. AB - AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-kappaB expression in multiple organs of SAP rats as well as the mechanisms involved. METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathological score of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-alpha contents in blood. The tissue microarray was used to detect the expression levels of NF-kappaB p65 protein in multiple organs. RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-alpha levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-kappaB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-kappaB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-kappaB expression in the lung was found in any group. CONCLUSION: Dexamethasone can lower the amylase, endotoxin and TNF-alpha levels as well as mortality of SAP rats. NF-kappaB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-kappaB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis. PMID- 17278221 TI - Inhibitory effects of saikosaponin-d on CCl4-induced hepatic fibrogenesis in rats. AB - AIM: To investigate the suppressive effect of saikosaponin-d (SSd) on hepatic fibrosis in rats induced by CCl(4) injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha) and interleukins-6 (IL-6). METHODS: Hepatic fibrosis models were induced by subcutaneous injection of CCl(4) at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses (1.0, 1.5 and 2.0 mg/kg) once daily for 6 wk in combination with CCl(4), while the control group received olive oil instead of CCl(4). At the end of the experiment, rats were anesthetized and killed (except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in low-dose group). Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase (ALT), triglyeride (TG), albumin (ALB), globulin (GLB), hyaluronic acid (HA) and laminin (LN) in serum and the content of hydroxyproline (HYP) in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-alpha and IL 6 in liver homogenate was evaluated by enzyme-linked immunosorbent assay (ELISA) and the levels of NF-kappaBp65 and I-kappaBalpha in liver tissue were analyzed by Western blotting. RESULTS: Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-alpha and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SSd markedly reduced all the above parameters compared with the model group, especially in the medium group (ALT: 412 +/- 94.5 IU/L vs 113.76 +/- 14.91 IU/L, TG: 0.95 +/- 0.16 mmol/L vs 0.51 +/- 0.06 mmol/L, GLB: 35.62 +/- 3.28 g/L vs 24.82 +/- 2.73 g/L, HA: 42.15 +/- 8.25 ng/mL vs 19.83 +/- 3.12 ng/mL, LN: 27.56 +/- 4.21 ng/mL vs 13.78 +/- 2.57 ng/mL, HYP: 27.32 +/- 4.32 mug/mg vs 16.20 +/- 3.12 mug/mg, TNF-alpha: 4.38 +/- 0.76 ng/L vs 1.94 +/- 0.27 ng/L, IL-6: 28.24 +/- 6.37 pg/g vs 12.72 +/- 5.26 pg/g, respectively, P < 0.01). SSd also decreased ALB in serum (28.49 +/- 4.93 g/L vs 37.51 +/- 3.17 g/L, P < 0.05). Moreover, the expression of NF-kappaB p65 in the liver of treated groups was lower than that in model groups while the expression of I-kappaBalpha was higher in treated group than in model group (P < 0.01). The expression of NF kappaBp65 and TNF-alpha had a positive correlation with the level of HA in serum of rats after treatment with CCl(4) (r = 0.862, P < 0.01; r = 0.928, P < 0.01, respectively). CONCLUSION: SSd attenuates CCl(4)-induced hepatic fibrosis in rats, which may be related to its effects of hepato-protective and anti inflammation properties, the down-regulation of liver TNF-alpha, IL-6 and NF kappaBp65 expression and the increased I-kappaBalpha activity in liver. PMID- 17278222 TI - Protection of Veratrum nigrum L. var. ussuriense Nakai alkaloids against ischemia reperfusion injury of the rat liver. AB - AIM: To investigate the protective effects and possible mechanisms of Veratrum nigrum L.var. ussuriense Nakai alkaloids (VnA) on hepatic ischemia/reperfusion (I/R) injury in rats. METHODS: Forty male Wistar rats were randomly divided into four experimental groups (n = 10 in each): (A) Control group (the sham operation group); (B) I/R group (pretreated with normal saline); (C) Small-dose (10 microg/kg) VnA pretreatment group; (D) Large-dose (20 microg/kg) VnA pretreatment group. Hepatic ischemia/reperfusion (Hepatic I/R) was induced by occlusion of the portal vein and the hepatic artery for 90 min, followed by reperfusion for 240 min. The pretreatment groups were administered with VnA intraperitoneally, 30 min before surgery, while the control group and I/R group were given equal volumes of normal saline. Superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity and nitric oxide (NO) content in the liver tissue at the end of reperfusion were determined and liver function was measured. The expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin (ES) were detected by immunohistochemical examinations and Western blot analyses. RESULTS: The results showed that hepatic I/R elicited a significant increase in the plasma levels of alanine aminotransferase (ALT: 74.53 +/- 2.58 IU/L vs 1512.54 +/- 200.76 IU/L, P < 0.01) and lactic dehydrogenase (LDH: 473.48 +/- 52.17 IU/L vs 5821.53 +/- 163.69 IU/L, P < 0.01), as well as the levels of MPO (1.97 +/- 0.11 U/g vs 2.57 +/- 0.13 U/g, P < 0.01) and NO (69.37 +/- 1.52 micromol/g protein vs 78.39 +/- 2.28 micromol/g protein, P < 0.01) in the liver tissue, all of which were reduced by pretreatment with VnA, respectively (ALT: 1512.54 +/- 200.76 IU/L vs 977.93 +/ 89.62 IU/L, 909.81 +/- 132.76 IU/L, P < 0.01, P < 0.01; LDH: 5821.53 +/- 163.69 IU/L vs 3015.44 +/- 253.01 IU/L, 2448.75 +/- 169.4 IU/L, P < 0.01, P < 0.01; MPO: 2.57 +/- 0.13 U/g vs 2.13 +/- 0.13 U/g, 2.07 +/- 0.05 U/g, P < 0.01, P < 0.01; NO: 78.39 +/- 2.28 micromol/g protein vs 71.11 +/- 1.73 micromol/g protein, 68.58 +/- 1.95 micromol/g protein, P < 0.05, P < 0.01). The activity of SOD (361.75 +/- 16.22 U/mg protein vs 263.19 +/- 12.10 U/mg protein, P < 0.01) in the liver tissue was decreased after I/R, which was enhanced by VnA pretreatment (263.19 +/ 12.10 U/mg protein vs 299.40 +/- 10.80 U/mg protein, 302.09 +/- 14.80 U/mg protein, P < 0.05, P < 0.05). Simultaneously, the histological evidence of liver hemorrhage, polymorphonuclear neutrophil infiltration and the overexpression of ICAM-1 and E-selectin in the liver tissue were observed, all of which were attenuated in the VnA pretreated groups. CONCLUSION: The results demonstrate that VnA pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of antioxidant capacity, reduction of inflammatory responses and suppressed expression of ICAM-1 and E-selectin. PMID- 17278223 TI - Gastrointestinal symptoms in a Japanese population: a health diary study. AB - AIM: To investigate the incidence of gastrointestinal symptoms and the nature of consequent utilization of health care services in a Japanese population. METHODS: Using self-report, we conducted a prospective cohort study of a nationally representative sample of the Japanese population over a one-month period to determine the incidence of gastrointestinal symptoms of all kinds and resultant health care utilization. Both information on visits to physicians and use of complementary and alternative medicine therapies were collected. RESULTS: From a total of 3568 in the recruitment sample, 3477 participants completed a health diary (response rate 97%). The data of 112 participants with baseline active gastrointestinal diseases were excluded from the analysis, leaving 3365 participants in the study. The incidence of gastrointestinal symptoms was 25% and the mean number of symptomatic episodes was 0.66 in a month. Abdominal pain, diarrhea, nausea, constipation and dyspepsia were the most frequent symptoms. Female gender, younger age, and low baseline quality of life were risk factors for developing these symptoms. The participants were more likely to treat themselves, using dietary, complementary or alternative medicines, than to visit physicians, except in the case of vomiting. CONCLUSION: Gastrointestinal symptoms are common in the Japanese population, with an incidence of 25%. Abdominal pain, diarrhea, nausea, constipation and dyspepsia are the most frequent symptoms. Risk factors for developing these symptoms include female gender, younger age, and low baseline quality of life. PMID- 17278224 TI - Recent i.v.-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon: an open-label pilot study. AB - AIM: To investigate the use of high dose consensus-interferon in combination with ribavirin in former iv drug users infected with hepatitis C. METHODS: We started, before pegylated (PEG)-interferons were available, an open-label study to investigate the efficacy and tolerability of high dose induction therapy with consensus interferon (CIFN) and ribavirin in treatment of naiive patients with chronic hepatitis C. Fifty-eight patients who were former iv drug users, were enrolled receiving 18 microg of CIFN daily for 8 wk, followed by 9 mug daily for up to wk 24 or 48 and 800 mg of ribavirin daily. End point of the study was tolerability and eradication of the virus at wk 48 and sustained virological response at wk 72. RESULTS: More than 62% of patients responded to the treatment with CIFN at wk 24 or 48, respectively, showing a negative qualitative PCR [genotype 1 fourteen patients (56%), genotype 2 five (50%), genotype 3 thirteen (87%), genotype 4 four (50%)]. Forty-eight percent of genotype 1 patients showed sustained virological response (SVR) six months after the treatment. CONCLUSION: CIFN on a daily basis is well tolerated and side effects like leuko- and thrombocytopenia are moderate. End of therapy (EOT) rates are slightly lower than the newer standard therapy with pegylated interferons. CIFN on a daily basis might be a favourable therapy regimen for patients with GT1 and high viral load or for non-responders after failure of standard therapy. PMID- 17278225 TI - Elastic band ligation of hemorrhoids: flexible gastroscope or rigid proctoscope? AB - AIM: To compare rigid proctoscope and flexible endoscope for elastic band ligation of internal hemorrhoids. METHODS: Patients between 18 and 80 years old, with chronic complaints (blood loss, pain, itching or prolapse) of internal hemorrhoids of grade 1-3, were randomized to elastic band ligation by rigid proctoscope or flexible endoscope (preloaded with 7 bands). Patients were re treated every 6 wk until the cessation of complaints. Evaluation by three dimensional anal endosonography was performed. RESULTS: Forty-one patients were included (median age 52.0, range 27-79 years, 20 men). Nineteen patients were treated with a rigid proctoscope and twenty two with a flexible endoscope. Twenty nine patients had grade 1 hemorrhoids, 9 patients had grade 2 hemorrhoids and 3 patients had grade 3 hemorrhoids. All patients needed a minimum of 1 treatment and a maximum of 3 treatments. A median of 4.0 bands was used in the rigid proctoscope group and a median of 6.0 bands was used in the flexible endoscope group (P < 0.05). Pain after ligation tended to be more frequent in patients treated with the flexible endoscope (first treatment: 3 vs 10 patients, P < 0.05). Three-dimensional endosonography showed no sphincter defects or alterations in submucosal thickness. CONCLUSION: Both techniques are easy to perform, well tolerated and have a good and fast effect. It is easier to perform more ligations with the flexible endoscope. Additional advantages of the flexible scope are the maneuverability and photographic documentation. However, treatment with the flexible endoscope might be more painful and is more expensive. PMID- 17278226 TI - Immunohistochemical analysis of p53, cyclinD1, RB1, c-fos and N-ras gene expression in hepatocellular carcinoma in Iran. AB - AIM: To study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS: Paraffin-embedded tissue samples of 25 patients (18 males and 7 females) with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during 2000-2001, and stained using immunohistochemistry method (avidin-biotin-peroxidase) for detection of p53, cyclinD1, RB1, c-fos and N-ras proteins. RESULTS: Six (24%), 5 (20%), 12 (48%) and 2 samples (8%) were positive for p53, cyclinD1, C-fos and N-ras expression, respectively. Twenty-two (88%) samples had alterations in the G1 cell-cycle checkpoint protein expression (RB1 or cyclinD1). P53 positive samples showed a higher (9 times) risk of being positive for RB1 protein than p53 negative samples. Loss of expression of RB1 in association with p53 over-expression was observed in 4 (66.7%) of 6 samples. Loss of expression of RB1 was seen in all cyclinD1 positive, 20 (90.9%) N-ras negative, and 11 (50%) C-fos positive samples, respectively. CyclinD1 positive samples showed a higher (2.85 and 4.75 times) risk of being positive for c-fos and N-ras expression than cyclinD1 negative samples. CONCLUSION: The expression of p53, RB1 and c-fos genes appears to have a key role in the pathogenesis of hepatocellular carcinoma in Iran. Simultaneous overexpression of these genes is significantly associated with their loss of expression during development of hepatocellular carcinoma. PMID- 17278227 TI - Achalasia and thyroid disease. AB - AIM: To investigate some possible etiologies of achalasia by screening patients with achalasia for some autoimmune diseases such as thyroid disease. METHODS: We examined 30 known cases of achalasia (20 females, 10 males). Their age ranged 15 70 years. All of them were referred to our institute for treatment. Their sera were evaluated to detect some possible associations with rheumatoid disease, thyroid disease, inflammatory process, anemia, etc. RESULTS: Seven out of 30 patients (23%) had thyroid disease including four patients with hypothyroidism (13.3%), two patients with hyperthyroidism (6.6%), and one had only thyroid nodule but was in euthyroid state (3.3%). Two of these hypothyroid patients had no related clinical symptoms (subclinical) and two had clinical manifestations of hypothyroidism. There were no correlations between the intensity of thyroid diseases and the severity of achalasia symptoms. CONCLUSION: The etiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. Thyroid disease presents concomitantly with achalasia in about one fourth of our patients who may have a common etiology. PMID- 17278228 TI - Analysis of immune responses against H pylori in rabbits. AB - AIM: To investigate the immunogenicity of H pylori proteins, to evaluate the production rate of anti H pylori IgG antibodies in relation to time and to demonstrate the fidelity of newly optimized in-house enzyme-linked immunosorbent assay (ELISA) technique as an alternative for H pylori infection assay. METHODS: In the present study, 100 microg of formalin-fixed H pylori whole cell antigens was injected into an experimental animal (New Zealand white female rabbit) intramuscularly on d 0, 16, 27 and 36. The first two doses were injected with adjuvants. On d 0, a serum sample was collected from the rabbit before immunization and this pre-immunized serum was used as a negative control for the whole study. To evaluate the immunogenic responses of the injected antigen, serum samples were collected from the rabbit at regular intervals up to d 42. The sera were analyzed using in-house ELISA and Western blot techniques. RESULTS: The production of anti H pylori IgG antibodies in the rabbit in response to the injected antigen increased almost exponentially up to d 14 and after that it was maintained at the same level until the last day (d 42). By analyzing the immune profiles of immunized sera, 11 proteins were identified to be immunogenic, among them 2 (approximately 100 kDa and 85 kDa) were most prominent. CONCLUSION: Analysis of the immune responses against pathogenic microorganisms like H pylori is necessary for the development of various diagnostic and preventive approaches. The results of this experiment reveal that the formalin-fixed H pylori whole cell antigens injected into the rabbit are highly immunogenic. These prominent proteins (approximately 100 kDa and 85 kDa) might have higher immunogenic effects among humans infected with H pylori and some of these immunogenic proteins can be included in diagnostic approaches based on serology and also for vaccine formulation. The in-house ELISA is a promising alternative compared to invasive techniques. PMID- 17278229 TI - Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats. AB - AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and beta-carotene levels were measured in all the groups. RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 +/- 2.81 vs 13.15 +/- 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and beta-carotene levels. CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity. PMID- 17278230 TI - Distribution of trace metal concentrations in paired cancerous and non-cancerous human stomach tissues. AB - AIM: To assess whether trace metal concentrations (which influence metabolism as both essential and non-essential elements) are increased or decreased in cancerous tissues and to understand the precise role of these metals in carcinogenesis. METHODS: Concentrations of trace metals including Cd, Ni, Cu, Zn, Fe, Mg and Ca in both cancerous and non-cancerous stomach tissue samples were determined by atomic absorption spectrometry (AAS). Tissue samples were digested using microwave energy. Slotted tube atom trap was used to improve the sensitivity of copper and cadmium in flame AAS determinations. RESULTS: From the obtained data in this study, the concentrations of nickel, copper and iron in the cancerous human stomach were found to be significantly higher than those in the non-cancerous tissues, by using t-test for the paired samples. Furthermore, the average calcium concentrations in the cancerous stomach tissue samples were found to be significantly lower than those in the non-cancerous stomach tissue samples by using t-test. Exceedingly high Zn concentrations (207-826 mg/kg) were found in two paired stomach tissue samples from both cancerous and non-cancerous parts. CONCLUSION: In contrast to the literature data for Cu and Fe, the concentrations of copper, iron and nickel in cancerous tissue samples are higher than those in the non-cancerous samples. Furthermore, the Ca levels are lower in cancerous tissue samples than in non-cancerous tissue samples. PMID- 17278231 TI - Evaluation of the effect of partial splenic embolization on platelet values for liver cirrhosis patients with thrombocytopenia. AB - AIM: To investigate the effect of partial splenic embolization (PSE) on platelet values in liver cirrhosis patients with thrombocytopenia and to determine the effective embolization area for platelet values improvement. METHODS: Blood parameters and liver function indicators were measured on 10 liver cirrhosis patients (6 in Child-Pugh grade A and 4 in grade B) with thrombocytopenia (platelet values < 80 x 10(3)/microL) before embolization. Computed tomography scan was also needed in advance to acquire the splenic baseline. After 2 to 3 d, angiography and splenic embolization were performed. A second computed tomography scan was made to confirm the embolization area after 2 to 3 wk of embolization. The blood parameters of patients were also examined biweekly during the 1 year follow-up period. RESULTS: According to the computed tomography images after partial splenic embolization, we divided all patients into two groups: low (< 30%), and high (> or = 30%) embolization area groups. The platelet values were increased by 3 times compared to baseline levels after 2 wk of embolization in high embolization area group. In addition, there were significant differences in platelet values between low and high embolization area groups. GPT values decreased significantly in all patients after 2 wk of embolization. The improvement in platelet and GPT values still persisted until 1 year after PSE. In addition, 3 of 4 (75%) Child-Pugh grade B patients progressed to grade A after 2 mo of PSE. The complication rate in < 30% and > or = 30% embolization area groups was 50% and 100%, respectively. CONCLUSION: Partial splenic embolization is an effective method to improve platelet values and GPT values in liver cirrhosis patients with thrombocytopenia and the > or = 30% embolization area is meaningful for platelet values improvement. The relationship between the complication rate and embolization area needs further studies. PMID- 17278232 TI - Therapeutic effects of caspase-1 inhibitors on acute lung injury in experimental severe acute pancreatitis. AB - AIM: To assess the therapeutic effect of Caspase-1 inhibitors (ICE-I) on acute lung injury (ALI) in experimental severe acute pancreatitis (SAP). METHODS: Forty two SD rats were randomly divided into 3 groups: healthy controls (HC, n = 6); SAP-S group (n = 18); SAP-ICE-I group (n = 18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion. In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum IL-1beta was measured by ELISA. Intrapulmonary expression of Caspase-1, IL-1beta and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated. RESULTS: Serum IL-1beta levels in SAP-S group were 276.77 +/- 44.92 pg/mL at 6 h, 308.99 +/- 34.95 pg/mL at 12 h, and 311.60 +/ 46.51 pg/mL at 18 h, which were increased significantly (P < 0.01, vs HC). In SAP-ICE-I group, those values were decreased significantly (P < 0.01, vs SAP-S). Intrapulmonary expression of Caspase-1, IL-1beta and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group (P < 0.01, vs HC). The expression of IL-1beta and IL-18 mRNA were decreased significantly in the SAP-ICE-I group (P < 0.01, vs SAP-S), whereas Caspase-1 mRNA expression had no significant difference (P > 0.05). The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly (P < 0.05 at 6 h, P < 0.01 at 12 h and 18 h, vs HC) and they were decreased significantly in the SAP ICE-I group (P < 0.05, vs SAP-S). Caspase-1 inhibitors ameliorated the severity of ALI in SAP. CONCLUSION: Caspase-1 activation, and overproduction of IL-1beta and IL-18 play an important role in the course of ALI, and Caspase-1 inhibition is effective for the treatment of ALI in experimental SAP. PMID- 17278233 TI - Evaluation of prognostic markers in severe drug-induced liver disease. AB - AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hyos rule and the most important predictors for outcome. METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed. RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD, and 140 (52.8%) of them were female. hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminant hepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52 85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012). CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal medicine stands out as the most common drug for DILD. While antitubercular drugs are found to be the primary etiological factor for fetal DILD, hepatic encephalopathy, ascites, jaundice, alcohol abuse and direct bilirubin levels are associated with the death of DILD patients. PMID- 17278235 TI - A case of acute infectious mononucleosis presenting with very high ferritin. AB - Hepatitis is an important but uncommon manifestation of acute Epstein Barr infection. Infectious mononucleosis is usually a disease of young adults. We report a case of infectious mononucleosis in a 72-year old jaundiced gentleman with ferritin level of 2438 that normalised on clinical improvement. PMID- 17278234 TI - Diagnosis and management of colonic injuries following blunt trauma. AB - AIM: To retrospectively evaluate the preoperative diagnostic approaches and management of colonic injuries following blunt abdominal trauma. METHODS: A total of 82 patients with colonic injuries caused by blunt trauma between January 1992 and December 2005 were enrolled. Data were collected on clinical presentation, investigations, diagnostic methods, associated injuries, and operative management. Colonic injury-related mortality and abdominal complications were analyzed. RESULTS: Colonic injuries were caused mainly by motor vehicle accidents. Of the 82 patients, 58 (70.3%) had other associated injuries. Laparotomy was performed within 6 h after injury in 69 cases (84.1%), laparoscopy in 3 because of haemodynamic instability. The most commonly injured site was located in the transverse colon. The mean colon injury scale score was 2.8. The degree of faecal contamination was classified as mild in 18 (22.0%), moderate in 42 (51.2%), severe in 14 (17.1%), and unknown in 8 (9.8%) cases. Sixty-seven patients (81.7%) were treated with primary repair or resection and anastomosis. Faecal stream diversion was performed in 15 cases (18.3%). The overall mortality rate was 6.1%. The incidence of colonic injury-related abdominal complications was 20.7%. The only independent predictor of complications was the degree of peritoneal faecal contamination (P = 0.02). CONCLUSION: Colonic injuries following blunt trauma are especially important because of the severity and complexity of associated injuries. A thorough physical examination and a combination of tests can be used to evaluate the indications for laparotomy. One stage management at the time of initial exploration is most often used for colonic injuries. PMID- 17278236 TI - An autopsy case showing massive fibrinoid necrosis of the portal tracts of the liver with cholangiographic findings similar to those of primary sclerosing cholangitis. AB - An 81-year-old Japanese man with jaundice was strongly suspected clinically of having primary sclerosing cholangitis based on clinical examinations and later died of hepatic failure. The entire course of the disease lasted about 10 mo. The autopsy revealed extensive fibrinoid necrosis in the liver, kidney, spleen, pancreas, lung, lymph nodes, and pleura. Particularly extensive fibrinoid necrosis in the portal tracts of the liver induced severe stenoses of the intrahepatic bile ducts, resulting in cholestasis in association with prominent liver injury. There were no findings indicating primary sclerosing cholangitis. The hepatic lesions in this case did not coincide with any known disease including collagen diseases. To clarify the cause of irregular stenoses of the intrahepatic biliary trees on cholangiographic findings, we postulate that some form of immunological derangement might be involved in pathogenesis of fibrinoid necrosis. However, the true etiology remains unknown. PMID- 17278237 TI - Pouchitis and pre-pouch ileitis developed after restorative proctocolectomy for ulcerative colitis: a case report. AB - We report a case of pouchitis and pre-pouch ileitis, and inflammation in the neo terminal ileum proximal to the pouch, developed after restorative proctocolectomy for ulcerative colitis. A 35-year old female presented with fever and abdominal pain five weeks after ileostomy closure following proctocolectomy. Computed tomography showed collection of feces in the pouch and proximal ileum. A drainage tube was placed in the pouch perianally, and purulent feces were discharged. With antibiotic treatment, her symptoms disappeared, but two weeks later, she repeatedly developed fever and abdominal pain along with anal bleeding. Pouchscopy showed mucosal inflammation in both the pouch and the pre-pouch ileum. The mucosal cytokine production was elevated in the pouch and pre-pouch ileum. With antibiotic and corticosteroid therapy, her symptoms were improved along with improvement of endoscopic inflammation and decrease of mucosal cytokine production. The fecal stasis with bacterial overgrowth is the major pathogenesis of pouchitis and pre-pouch ileitis in our case. PMID- 17278238 TI - Cytomegalovirus hepatitis and myopericarditis. AB - Cytomegalovirus (CMV) infection in inmunocompetent hosts generally is asymptomatic or may present as a mononucleosis syndrome but rarely can lead to severe organ complications. We report a case of simultaneous hepatic and pericardic CMV infection in a 36-year old immunocompetent man. He was admitted to coronary unit with fever, chest pain radiated to shoulders, changes on electrocardiogram with diffuse ST elevation and modest laboratory elevations in the MB fraction of creatine kinase (CK-MB) of 33.77 microg/L (0.1-6.73), serum cardiac troponin T of 0.904 ng/mL (0-0.4), creatine kinase of 454 U/L (20-195) and myoglobin of 480.4 microg/L (28-72). Routine laboratory test detected an elevation of aminotransferase level: alanine aminotransferase 1445 U/L, aspartate aminotransferase 601 U/L. We ruled out other causes of hepatitis with normal results except IgM CMV. The patient was diagnosed with myopericarditis and hepatitis caused by cytomegalovirus and started symptomatic treatment with salicylic acid. In few days the laboratory findings became normal and the patient was discharged. PMID- 17278240 TI - Treatment regimen design in clinical radiotherapy for hepatoma. PMID- 17278239 TI - Indian patients with nonalcoholic fatty liver disease presenting with raised transaminases are different at presentation. PMID- 17278241 TI - Drug advertising. GAO spurs advocates to urge FDA fast-track oversight of drug ads. PMID- 17278243 TI - Sentencing. HIV-positive inmate gets 10 more years for biting officer. PMID- 17278242 TI - Funding. CARE Act passage could bring new services to rural patients. PMID- 17278244 TI - Prevention. United Nations to review circumcision recommendations. PMID- 17278245 TI - Self-proclaimed South African AIDS activists denied asylum. PMID- 17278246 TI - Consolidation is granted in 4 HIV defamation cases. PMID- 17278248 TI - HIV and prisons. Number of HIV-positive inmates decreases for 5th straight year. PMID- 17278247 TI - Judge to decide on interstate HIV exposure case. PMID- 17278249 TI - Prisons. PLRA's 3-strike rule works against HIV-positive prisoner. PMID- 17278250 TI - Pandemic. United Nations details progress in fight against AIDS. PMID- 17278251 TI - PLRA trips up inmate's unlawful HIV-disclosure claim. PMID- 17278253 TI - Sentencing. Civil commitment affirmed for HIV-positive sexual offender. PMID- 17278252 TI - Prisoner's HIV, TB exposure claim survives dismissal. PMID- 17278254 TI - Outbreak news. Yellow fever, Togo. PMID- 17278255 TI - Respecting the power of denial. PMID- 17278256 TI - Studying students in Montessori schools. PMID- 17278257 TI - Israeli doctors resist HIV testing of surgeons. PMID- 17278258 TI - World's first public-private cord blood bank launched in United Kingdom. PMID- 17278260 TI - Magnetic counter-gravity flow separation of electrically prepolarised lymphoid cells. AB - A novel principle is proposed for a differential separation of live cells (such as leucocytes) from a main flow. A microfluidic device with planar insulated electrodes as the side walls of the channel was manufactured and tested. An array of insulated vertical conductor wires was inserted along the axis of the channel and used to impose Lorentz forces upon polarisable particles that moved with the flow. Polystyrene microspheres and lymphoid cell lines (DOHH2 and K562) were used to test the ability of the setting to impose a force field that induced consistent vertical motion. The direction of electric current was found to directly influence the number of cells or microspheres that were sampled at the surface of the flow. Lorentz force was considered to be active upon cells due to an overall polarisation of the membrane surface. The consequence of the magnetic force was that the polarised cells were moved vertically upwards (opposing gravity). The setting was effective for increasing the number of extracted cells from a main flow or for increasing the concentration of DOHH2 cells in a mixed population with K562 in culture medium. The limitations of the work parameters (potential-current) were found to be dependent upon the cell type. PMID- 17278259 TI - Improved outcome after relapse in children with acute myeloid leukaemia. AB - In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122 patients who received re induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival were duration of first complete remission (CR1) and stem cell transplantation (SCT) in CR1. In early relapse (<1 year in CR1), survival was 21 +/- 5% compared with 48 +/- 6% in late relapse. For children receiving re-induction therapy, survival in early relapse was 29 +/- 6% and 51 +/- 6% in late. Patients treated in CR1 with SCT, autologous SCT or chemotherapy had a survival of 18 +/- 9, 5 +/- 5 and 41 +/- 5%, respectively. Survival was 62 +/- 6% in 64 children given SCT as part of their relapse therapy. A significant proportion of children with relapsed AML can be cured, even those with early relapse. Children who receive re-induction therapy, enter remission and proceed to SCT can achieve a cure rate of 60%. PMID- 17278261 TI - Activated platelet-derived microparticles in thalassaemia. AB - Thromboembolic complications have been documented in thalassaemia patients. The aggregability of abnormal red blood cells and the high level of membrane-derived microparticles (MPs) stemming from blood cells are thought to be responsible for the associated thrombotic risk. We investigated the number of MPs, their cellular origin and their procoagulant properties in beta-thalassaemia. Fresh whole blood was simultaneously stained for annexin V, cellular antigens and the known density beads. The procoagulant properties of these phosphatidylserine (PS)-bearing MPs were also measured by assessing the platelet factor-3-like activity in the blood. Flow cytometric results showed that splenectomised beta-thalassaemia/HbE patients had significantly higher levels of PS-bearing MPs than non-splenectomised beta thalassaemia/HbE patients and normal individuals (P < 0.0001). There was a good correlation between PS-bearing MPs and PS-bearing platelets, reflecting the existence of chronic platelet activation in beta-thalassaemia/HbE patients (r(s) = 0.511, P < 0.001). The cellular origin of PS-bearing MPs showed mostly activated-platelet origin with adhesion (CD41a/CD62P/CD36). Moreover, the platelet procoagulant activity was higher in splenectomised beta-thalassaemia/HbE patients when compared with non-splenectomised (P < 0.05) and normal individuals (P < 0.01), and the amount correlated with PS-bearing MPs (rs = 0.560, P < 0.001). These findings suggest that MPs originate from activated platelets with a potential to aggravate thrombotic events when the numbers are excessive, as is commonly seen in splenectomised beta-thalassaemia/HbE patients. PMID- 17278263 TI - Epstein-Barr virus early-antigen antibodies before allogeneic haematopoietic stem cell transplantation as a marker of risk of post-transplant lymphoproliferative disorders. AB - The occurrence of post-transplant lymphoproliferative disorders (PTLDs) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents a clinical problem. Pretransplant Epstein-Barr virus serological status and viral load was determined in 21 recipients and 28 control transplanted patients, with (+) and without (-) PTLD, respectively. Early-antigen immunoglobulin G (EA-IgG) was detected in 12/21 PTLD+ patients, but only 2/28 PTLD patients (P = 0.00023, Odds ratio = 17.42). High viral load was detected in peripheral blood mononuclear cells at PTLD diagnosis, independently of deleted LMP1. Detection of EA-IgG in allo-HSCT recipients pretransplantation might be considered as risk factor for PTLD development. PMID- 17278264 TI - Comparison of the survival implications of tumour-associated versus cancer-testis antigen expression in acute myeloid leukaemia. PMID- 17278262 TI - Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms. AB - This study was undertaken to further elucidate the biological mechanisms underlying the frequent event of transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL). The gene expression profiles of 20 paired lymph node biopsies, derived from the same patient pre- and post-transformation, were analysed using the Lymphochip cDNA microarray. TP53 mutation analysis was performed and copy number alterations at the c-REL and CDNK2A examined. Immunohistochemistry was performed on an independent panel of paired transformation paraffin-embedded samples. Transformed follicular lymphoma was predominantly of the germinal centre B-like phenotype both at the mRNA and protein level. Despite this homogeneity, transformation proceeded by at least two pathways. One mechanism was characterised by high proliferation, as assessed by the co-ordinately expressed genes of the proliferation signature. This group was associated with the presence of recurrent oncogenic abnormalities. In the remaining cases, proliferation was not increased and transformation proceeded by alternative routes as yet undetermined. Genes involved in cellular proliferation prevailed amongst those that were significantly increased upon transformation and T cell and follicular dendritic-associated genes predominated amongst those that decreased. t-FL is a germinal centre B (GCB)-like malignancy that evolves by two pathways, one that is similar in proliferation rate to the antecedent FL and the other that has a higher proliferation rate and is characterised by the presence of recognised oncogenic abnormalities. PMID- 17278265 TI - Inappropriate use of meta-analysis to estimate efficacy of probiotics. PMID- 17278266 TI - Barrett's esophagus and obesity. PMID- 17278267 TI - Inflammatory bowel disease in young children. PMID- 17278268 TI - What about endoscopic invisible Barrett's esophagus? PMID- 17278269 TI - Bugs be gone? Prophylaxis of infection in acute pancreatitis. PMID- 17278270 TI - Osteoporosis and inflammatory bowel disease. PMID- 17278271 TI - Palmar lipid deposits and profound hypercholesterolemia that resolved after orthotopic liver transplantation for primary biliary cirrhosis. PMID- 17278272 TI - Smoking and DNA mismatch repair polymorphisms in colorectal polyps and cancer. PMID- 17278273 TI - Urinary sodium/potassium ratio on random sample as a useful tool to assess diuretic-induced natriuresis on chronic liver disease-associated ascitis. PMID- 17278274 TI - Pitfalls of cyst fluid findings obtained by endoscopic ultrasonography fine needle aspiration on a pancreatic lymphoepithelial cyst. PMID- 17278275 TI - Pulmonary aspiration of a capsule endoscope. PMID- 17278276 TI - HBsAg-negative HBV mutant transfusion-related acute hepatitis B. PMID- 17278277 TI - Transient type III atrioventricular block after infliximab infusion in a fistulizing perianal Crohn's disease patient. PMID- 17278278 TI - Bedside examination of the stomach through PEG catheters using a superthin, battery-powered endoscope. PMID- 17278279 TI - Effective steroid pulse therapy for the biliary stenosis caused by autoimmune pancreatitis. PMID- 17278284 TI - For the patient. What causes diabetes in Japanese Brazilians? PMID- 17278280 TI - Obesity. PMID- 17278285 TI - For the patient. Preeclampsia among pregnant women: high blood pressure and protein in the urine. PMID- 17278286 TI - For the patient. Simple steps to control congestive heart failure. PMID- 17278287 TI - For the patient. Breast-conserving surgery and radiation therapy: do the two go hand-in-hand as recommended? PMID- 17278289 TI - Preventing bedsores. They can be painful and deadly. The good news is that a few simple steps can keep many bedsores from reaching that stage. PMID- 17278288 TI - For the patient. A higher calcium intake may be important in weight loss diets. PMID- 17278291 TI - Hot stuff has the right stuff. PMID- 17278292 TI - Is overweight okay? PMID- 17278290 TI - Metformin: now or later? PMID- 17278293 TI - When arteries get inflamed. Headaches are the most common symptom of temporal arteritis, but the anemia, weight loss, and malaise it produces means other diseases are often suspected. PMID- 17278294 TI - Giving cancer its walking papers. Research demonstrates that exercise benefits cancer patients. PMID- 17278295 TI - By the way, doctor. I've been out in the sun all my life. My forehead has been sunburned a thousand times. I now wear a hat. Is there something I could use to repair the damage to the areas of my forehead that have been sunburned too much? PMID- 17278296 TI - Low back pain: causes, symptoms, and diagnosis. PMID- 17278297 TI - Exercise and malignancy: can you walk away from cancer? PMID- 17278298 TI - Food for thought: the polymeal. PMID- 17278299 TI - On call. Last month I developed severe weakness on the whole left side of my face. My doctor diagnosed Bell's palsy and referred me to a neurologist. I recovered before I got to see her, so I didn't keep the appointment. Although my face is now back to normal, I'd like to know more about the condition. What can you tell me? PMID- 17278300 TI - Bronchodilator use in asthma: the art of prescribing bronchodilators correctly, taking advantage of their differences and reducing risks. PMID- 17278301 TI - Evaluating the efficiency of polymerase chain reaction in diagnosing pulmonary tuberculosis in indigenous and non-indigenous patients. PMID- 17278302 TI - Prevalence of asthma in the Federal District of Brasilia, Brazil. PMID- 17278303 TI - Peak expiratory flow. It's better to measure! PMID- 17278304 TI - Brazilian ratification of the Framework Convention on Tobacco Control: a question of public health. PMID- 17278305 TI - The frequency of benign prostate hypertrophy in Calabar. AB - The present study was to find out through histopathological records the most frequently occurring disease of the prostate from suspected prostate diseases in Calabar, Cross River State, Nigeria. A total number of 324 cases of prostatic biopsies and autopsy materials recorded in the histopathology laboratory of the University of Calabar Teaching Hospital (UCTH), Calabar between 1986 and 1995 were used for this study. Benign prostatic hypertrophy was observed as the major pathology among all the diseases of the prostate gland recorded in UCTH in Calabar having accounted for 76.3% (261 out of 342) while prostatic carcinoma accounted for 19% (65 out of 324), rest 4.7% (16 out of 342) were inflammatory lesions. The result indicated that benign prostatic hypertrophy occurs in men from 40 years and above. The frequency increased with age, reaching a maximum of 34.5% (90 out of 261) in the age group (70-79) years old. The people in Cross River State should be informed of the high frequency of benign prostatic hypertrophy and should be advised to seek health care promptly in suspected prostate related illness. PMID- 17278306 TI - Pulmonary infiltrates in critically ill patients: the importance of lung biopsy. PMID- 17278307 TI - Pediatric asthma--the impact of hospital admissions. PMID- 17278308 TI - Core biopsy; tru-cut biopsy, lance biopsy or punch biopsy with a tissue-cutting needle (punch cutting--PCut)? PMID- 17278309 TI - Scientific production of the Brazilian Society of Pulmonology and Phthisiology: 1979-2006. PMID- 17278310 TI - Respiratory sleep disorders and fibromyalgia. PMID- 17278311 TI - Pulmonologists, awake! PMID- 17278312 TI - Bibliography. Current world literature. Protein and amino acid metabolism. PMID- 17278313 TI - Acute laryngeal obstruction in a Nigerian Hospital: Clinical presentation and management. AB - OBJECTIVES: To determine the clinical presentations and management of patients with acute laryngeal obstruction. PATIENTS AND METHODS: A retrospective study of 36 patients with acute laryngeal obstruction to the accident and emergency unit (A&E), emergency paediatric unit (EPU) and the Ear, Nose and Throat diseases clinic (ENT) of the University of Ilorin Teaching Hospital between January 1998 and the December 2002 are presented. RESULTS: The age ranges of the patient were between 1.5 years to 46 years (mean age 29.6 years with male/female ratio of 2:1 Breathlessness (83.3%), hoarseness (66.7%), and noisy breathing (50%) were the main symptoms at presentation. CONCLUSIONS: These 36 patients represented 4.9 % of the in-patients seen by the Otolaryngologists during the period under review and 75% of cases of acute upper airway obstruction managed during this period. The commonest cause of obstruction in this study was laryngeal tumours (47.2%) laryngeal carcinoma (27.8%) in the adults and juvenile laryngeal papillomas (19.4%) in the paediatric age group; other causes were laryngeal infections (acute and chronic) represented 20% of aetiologic factors. Impacted laryngeal foreign bodies occurred in 5(13.9%) all in the paediatric age group. Eleven (30.6%) were managed conservatively with antibiotics and antikoch's therapy; 12(33.3%) had emergency tracheostomy prior to definitive treatment of direct laryngoscopy in 10 patients (27.8%) for biopsy, removal of foreign bodies and extirpations of juvenile laryngeal papillomas and 3(8.3%) were managed by endotracheal intubations. Health education of the public is recommended to ensure early presentation in hospital as soon as symptoms of laryngeal tumours are noticed and health care providers should refer such cases early. PMID- 17278314 TI - Ventilator-associated pneumonia. PMID- 17278315 TI - Commentary. Ultrasound measurement of the fibrous cap in symptomatic and asymptomatic atheromatous carotid plaques. PMID- 17278317 TI - Commentary. Human thrombin for treatment of pseudoaneurysms: comparison of bovine and human thrombin sonogram-guided injection. PMID- 17278316 TI - Histopathological findings in nephrectomy specimens--A review of 42 cases. AB - OBJECTIVE: This study aims at determining the histopathological findings in nephrectomy specimens in the University of Maiduguri Teaching Hospital. METHODS: A retrospective study of all cases of nephrectomies in UMTH between January 1993 and December 2003. RESULTS: There were 42 cases of unilateral nephrectomies, 26 (61.9%) males and 16 (38.1.9%) females giving a ratio of 1.6:1. Of these, 23 (54.8%) were benign and 19(45.2%) malignant. Chromic interstitial/pyelonephritis was the commonest indication for nephrectomy and this accounted for 28.6% of all cases. Nephroblastoma, the second commonest, accounted for 23.8% of all cases and is the major malignant indication for nephrectomies. Renal cell carcinoma and hydronephrosis accounted for 7(16.7%) cases each; polycystic kidney, transitional cell carcinoma and non-Hodgkin's lymphoma. CONCLUSION: There is need to emphasise the importance of early diagnosis and proper treatment of urinary tract infections, since chronic interstitial/pyelonephritis is the commonest indication for nephrectomy in our environment. This will go long way in reducing the rate nephrectomies on our patients. PMID- 17278318 TI - Commentary. Treating aortic dissection and penetrating aortic ulcer with stent graft: thirty cases. PMID- 17278319 TI - Commentary. Perioperative and long-term cardiovascular outcomes in patients undergoing endovascular treatment compared with open vascular surgery for abdominal aortic aneurysm or iliaco-femoro-popliteal bypass. PMID- 17278320 TI - Commentary. Neoaortic reconstruction for aortic graft infection: need for endovascular adjunctive therapies? PMID- 17278321 TI - Commentary. Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation. PMID- 17278322 TI - The metabolic syndrome: Review of current concepts. AB - The metabolic syndrome incorporates into a single entity, insulin resistance and its associated cluster of related cardiovascular metabolic risk factors including type 2 diabetes mellitus, essential hypertension, dyslipidamia and central obesity. Various hypotheses (thrifty genotype/phenotype, limbic-hypothalamic and altered homeostatic mechanisms) have been used to explain the interaction between genetic, intrauterine and environmental factors, leading to this enigmatic concept. Current interest addresses the roles of fat-derived adiponectin, inflammatory markers (C-reactive protein, leucocytes, interleukin and tumour necrosis factor), endothelial dysfunction and disordered haemostasis (plasminogen activator inhibitor-1 and fibrinogen). Angiotensin II, endothelin-1 and increased salt sensitivity contribute to the development of hypertension in metabolic syndrome. The main significance of the syndrome is the heightened risk of cardiovascular morbidity and mortality arising from increased atherogenic potential. Therapeutic interventions are multidimensional in approach, and aimed at enhancing insulin sensitivity and ameliorating the consequences of insulin resistance. Promotion of African native lifestyle characterised by high degree of physical activity and fibre diet is and appropriate tool for primary prevention of metabolic syndrome. PMID- 17278323 TI - Socio-demographic factors of adult malignant lymphomas in Benin City, Nigeria. AB - AIM: The aim of this study is to determine the incidence and sociodemographic factors associated with adult malignant lymphoma in Benin City, Niger Delta region of Nigeria. METHOD: A retrospective study of 205 patients with a diagnosis of lymphoma seen over a 13-year period (1990-2003) at the University of Benin Teaching Hospital, Nigeria. They were analyzed in the context of gender, marital status, geographical abode, educational and occupational status. The patients had sufficient data recorded at diagnosis to allow retrospective assignment into the various subtypes. RESULTS: There were 70 males and 135 females with a male-to female ratio of 1:1:9. Non-Hodgkin's lymphoma (NHL) was more frequent (83%) while Hodgkin's lymphoma had incidence of 17%. Marital status (P = 0.0002), geographical abode (p = 0.0046), educational (P = 0.0045) and occupational status (p = 0.0001) were significantly associated with the malignant lymphoma at presentation. All the lymphoma subtypes were most common in patients who resided in Delta state, a major oil producer. The majority of the lymphoma patients (46.3%) had tertiary form of education. The highest and lowest social classes were most likely to have lymphoma, which may have been related to age and industrial exposure. CONCLUSION: Poverty and illiteracy are additional problems with patients with malignant lymphomas. Living in Delta State where the petrochemical industries and gas flare sites are located may be a risk factor for the development of lymphoma. PMID- 17278325 TI - Congenital anomalies of the eye and adnexae in Edo State, Nigeria. AB - AIMS AND OBJECTIVES: Congenital ocular anomalies are the result of defective development of the ocular tissues during intrauterine life. The aim of this study was to increase awareness amongst Ophthalmologists and other healthcare providers on some cogenital ocular anomalies seen in clinical practice. PATIENTS AND METHODS: The 5 cases presented in this study were cases seen during our routine clinics at the University of Benin Teaching Hospital, Benin City, Edo State and Irrua Specialist Teaching Hospital, Edo State. Informed consent was obtained from the patients regarding the study and the illustrative photographs displayed in the study. Case reports of various congenital anomalies involving the eye and adnexae in Edo State, Nigeria seen over a 1-year period are presented. RESULTS: The first 2 cases were cases of clinical anophthalmos/micophthalmos. The causative factor in one of them was presumably maternal drug (traditional medicine) ingestion for a period of 5 months during pregnancy. The others were cases of dermoid cyst, congenital lid eversion and congenital corneal opacities. CONCLUSION: The literature on congenital anomalies of the eye and adnexae is briefly reviewed. PMID- 17278324 TI - [Insomnia and increased use of sleep medication among seniors: problems and alternative treatment]. AB - OBJECTIVE: To investigate the problem of insomnia and increased used of sleep medication among seniors and to look at an alternative form of treatment (cognitive-behavioural therapy [CBT]) that has been adapted specifically for this population. QUALITY OF EVIDENCE: MEDLINE and PsycINFO were searched from 1990 to 2005 using the key words insomnia, elderly (older adults), hypnotics (sleep medication), and cognitive behavior therapy. When discussing the efficacy of treatment, sources quoted offer level I evidence. Studies on the deleterious effects of hypnotics primarily offer level II evidence, so their findings must be interpreted with caution (some studies present conflicting results). MAIN MESSAGE: Insomnia in elderly people is associated with marked distress or deterioration in social or physical functioning. Hypnotics can be dangerous for elderly people because they raise the risk of adverse effects on cognitive function and the risk of drug-drug interactions. Treatment should be based on CBT alone or on a combination of CBT and appropriate pharmaceutical therapy. CONCLUSION: Cognitive-behavioural therapy adapted specifically to the problem of insomnia in seniors is one of the recommended options. The gains often include a notable decrease in use of sleep medication and in the emotional distress associated with insomnia. PMID- 17278326 TI - Idiopathic interstitial pneumonias in LUTH--A morphologic study of three cases. AB - OBJECTIVE: Idiopathic interstitial pneumonias are rarely diagnosed in our environment. However in in the year 2000 a group of new cases were histologically diagnosed in the Department of Morbid Anatomy of the Lagos University Teaching Hospital (LUTH). This study aims to review the clinical and morphologic features of the three cases or Idiopathic Interstitial Pneumonias seen at surgicals and autopsy over a 10 year period (March 1995 to March 2005) in LUTH; as well as discuss some clinicopathologic features of interstitial pneumonias. MATERIALS AND METHODS: A review of the cases seen at surgicals and autopsy from March 1995 to March 2005 was done by retrieving the relevant reports. Cases described with interstitial pneumonitis were re-evaluated and their respective paraffin blocks re-cut for special staining to better demonstrate the changes in morphology. RESULTS: A total of 3 cases were retrieved from the ten year period reviewed. Incidentally, all occurred in the year 2000. Their mean age was 57 years and the male to female ratio was 2:1. The 'Usual Interstitial Pneumonitis' pattern was more common. CONCLUSION: Interstitial pneumonias are rare in our environment; the apparent emergence of three cases in the year 2000 alone is a curiosity as a search over a ten year period (March 1995 to March 2005) yielded no other histologically convincing case. An increased index of clinical suspicion on the part of our clinicians and pathologists as well as collaborative research involving several specialists and Medical Institutions will be required to determine the true frequency of this disease in our environment and its peculiar clinicopathological features. PMID- 17278327 TI - [Microsociology and theoretical change: in the court of Mario Biagioli]. PMID- 17278328 TI - A bibliography of Marianna Paulucci (1835-1919). PMID- 17278329 TI - Migration over the life course in XIXth century Netherlands and the American north: a comparative analysis based on genealogies and population registers. PMID- 17278330 TI - Is there life outside the migrant network? German immigrants in XIXth century Netherlands and the need for a more balanced migration typology. PMID- 17278331 TI - [History and family on the route to Santiago de Compostela]. PMID- 17278332 TI - Antibody-induced failure of botulinum toxin type A therapy in a patient with masseteric hypertrophy. AB - BACKGROUND: With the expanding use of botulinum toxin, much concern about the antibody against botulinum toxin is arising. Unlike neurologic indications such as cervical dystonia, antibody-induced failure of botulinum toxin therapy has never been reported in the cosmetic field. OBJECTIVE: The objective was to describe a case of an antibody-induced failure of botulinum toxin type A (BTX-A) therapy (BOTOX, Allergan, Inc.) that occurred in a patient with masseteric hypertrophy. METHODS AND MATERIALS: We present a 20-year-old girl who developed antibody-induced therapy failure after the fourth injection series. Sixty units of toxin was injected at each series and the intertreatment interval was four to five months. RESULTS: Frontalis test revealed no paresis of muscle after a unilateral injection of BTX-A. Circulating antibodies against BTX-A were detected by indirect enzyme-linked immunosorbent assay and mouse protection assay. CONCLUSION: This case is unique in that, first, immunoresistance developed in a patient of cosmetic indication where only a small dose of BTX-A was administered and, second, antibodies developed on the so-called new formulation of BOTOX. Our case alerts cosmetic surgeons to the importance of antibody against the botulinum toxin. PMID- 17278333 TI - Professional misconduct--vasectomy procedures. PMID- 17278334 TI - Nothing natural is shameful: vestiges of a debate about sex and science in a group of Late Medieval manuscripts. PMID- 17278335 TI - [Critical notes on the text of Celsus's De medicina]. PMID- 17278336 TI - A multimethod approach to evaluate chemical dot thermometers for oral temperature measurement. AB - Limited research has explored the accuracy of chemical dot thermometers for oral temperature measurement in adults. This study was undertaken to assess the agreement between oral temperatures taken with an electronic thermometer and single-use chemical dot thermometers in healthy women undergoing surgical delivery. During operative delivery, oral temperatures taken every 15 minutes with both the reference electronic thermometer (ETT) and a Tempa.DOT (TDT) chemical dot thermometer were compared. Data were analyzed using paired t tests, the Bland and Altman plot, and the concordance correlation coefficient. The total number of paired observations for the 62 subjects was 212. The mean difference between the two measurements was 0.35 +/- 0.32 degrees C (p < .0001, 95% CI 0.31, 0.40). Additional analysis indicated a serious undermeasurement by TDT of ETT temperatures. Data from multiple methods of analysis indicate that the Tempa.DOT chemical dot thermometer significantly undermeasures ETT and is not a reliable indicator of oral temperature. PMID- 17278337 TI - Psychometric properties of the Readiness for Hospital Discharge Scale. AB - The purpose of the study was to assess the psychometrics properties of the Readiness for Hospital Discharge Scale (RHDS), a 23-item instrument that measures patients' perception of readiness for discharge. Data were obtained from 356 respondents from two urban tertiary medical centers (adult and children's) in the midwestern United States who were participants in a larger study of predictors and outcomes of readiness for hospital discharge. Confirmatory factor analysis, contrasted group comparisons, and predictive validity testing supported the 4 factor structure and construct validity of the instrument. Following deletion of two poorly performing items, Cronbach's alpha for the revised 21-item scale was 0.90. The RHDS can be a useful tool for measurement of readiness for discharge for clinical and research purposes. PMID- 17278338 TI - Psychometric properties of Spanish versions of the FACES II and Dyadic Adjustment Scale. AB - Although Hispanic Americans are one of the fastest growing ethnic populations in the United States, use and psychometric testing of Spanish versions of two instruments commonly used to measure quality of the couple's relationship and family functioning, the Dyadic Adjustment Scale (DAS) and the FACES II, have not been reported. The purpose of this study was to test the psychometric properties of the newly translated Spanish version of these two instruments. In this bilingual sample of 78 adults, internal consistencies were acceptable (.72 to .77 for the FACES II; .67 to .93 for the DAS) and test-retest correlations were high (.80 to .88 FACES II; .79 to .87 DAS). Correlations between the Spanish and English versions were also high (.87 to .94 FACES II; .91 to .99 DAS). Psychometric findings support the reliability and validity of the Spanish versions of these newly translated measures. PMID- 17278339 TI - Development and validation of the Health Care Satisfaction Questionnaire (HCSQ) in elders. AB - The Health Care Satisfaction Questionnaire (HCSQ) was designed for the evaluation of health care and services in a manner that controls acquiescence bias yet is characterized by a simple structure. The HCSQ was developed and validated within the context of the Program of Research to Integrate Services for the Maintenance of Autonomy (PRISMA) in the Sherbrooke and Quebec City areas of Quebec, Canada. Exploratory and confirmatory factor analyses were done with 873 subjects and confirmed the multidimensional nature of the concept of satisfaction. Three factors explained more than 52% of the total variance. The analysis of internal consistency produced Cronbach alpha coefficients of .93, .74, and .78 for Factors 1, 2, and 3, respectively. The alpha of the overall scale was .92. The intraclass correlation coefficient (test-retest) for the entire scale was .72 (95% CI: .52 .84). In light of these findings, the characteristics and multidimensional perspective of the HCSQ appear to be useful for measuring and advancing knowledge about health care and services satisfaction. PMID- 17278340 TI - Maternal Postpartum Quality of Life Questionnaire. AB - This article summarizes the development and psychometric properties of the first self-administered, paper-and-pencil instrument that measures maternal quality of life during the early postpartum period. The definition, domains, and conceptual model by Ferrans and Powers (QLI) were used to develop the Maternal Postpartum Quality of Life (MAPP-QOL) tool. A convenience sample of 184 mothers completed the MAPP-QOL at week 1 and 3 postpartum. Component analysis revealed five domains: psychological/baby; socioeconomic; relational/spouse-partner; relational/family-friends; and health & functioning. Internal consistency reliability for the five subscales resulted in Cronbach's alpha coefficients ranging from .82 to .96. Stability reliability ranged from .66 to .76. The MAPP QOL and a single-item measure of life satisfaction correlated (r = .69), suggesting convergent validity; discriminant validity was supported by negative correlations with the three negative mood states of the Multiple Affect Adjective Check List-Revised (MAACL-R) as well as poor sleep and fatigue scores. Acceptable reliability and construct validity suggest that the MAPP-QOL may be used in research. Further testing with larger and more diverse samples is recommended. PMID- 17278341 TI - The association of parental alcohol abuse and depression with severe emotional and behavioural problems in adolescents: a clinical study. AB - BACKGROUND: Earlier studies have indicated associations between parental psychiatric problems, such as depression, and substance abuse and adolescent problems. AIMS: This study aimed to determine whether parental psychiatric problems are associated with problems and problem behaviour in adolescents in a clinical sample. METHODS: The study subjects were 70 outpatient adolescents (age 13-18 years, boys 30%) and their parents. The adolescents were assessed using the structural clinical interview for DSM-III-R (SCID) and a semi-structured questionnaire, and the parents were interviewed using a semi-structured questionnaire. RESULTS: Maternal alcohol abuse and depression were associated with serious problems, especially among girls, and paternal alcohol abuse was associated with adolescent health-compromising behaviour. Maternal depression and alcohol abuse had no association with adolescent health-compromising behaviour. Maternal depression without alcohol abuse was associated with the diagnosis of major depressive disorder in adolescents, but not with other adolescent problems, while paternal depression without alcohol abuse was not associated with any adolescent problems. CONCLUSIONS: Despite the small study sample, these findings indicate that parental psychiatric problems and alcohol abuse are correlated with adolescent psychological problems and should be considered and assessed when assessing adolescents. PMID- 17278342 TI - Epidemiological studies on mental health needs of Asian population in New Zealand. AB - BACKGROUND: New Zealand has recently experienced a massive and rapid influx of Asian migrants. The Asian population has doubled in 10 years and is now the third largest ethnic group. MATERIALS: Databases reviewed include Medline, NZ government reports and NZ media releases. DISCUSSION: Despite the significant growth in the Asian population, most of whom are in a vulnerable age group for mental morbidity and are exposed to adverse experiences, accurate and systematically obtained information on the mental health of Asians is lacking. CONCLUSION: This paper argues for a need to conduct a well-designed epidemiological study on the mental health needs of Asians in New Zealand. Recommendations on how to pursue this epidemiological study are provided. PMID- 17278343 TI - Personal tragedy or system failure: a qualitative analysis of narratives of caregivers of people with severe mental illness in Hong Kong and Taiwan. AB - BACKGROUND: Most studies agree that mental illness brings a heavy objective and subjective burden of care on the family and especially the caregivers. However, very little attention has been paid to the wider context in which this burden is shaped and sustained. MATERIAL: In-depth interviews were conducted with 11 caregivers in Hong Kong and Taiwan and subsequent analysis identified four major themes: mystical knowledge beyond understanding, persistent self-blame and lay explanation, inertia of caregivers and non-responsive service system, and unsatisfying encounters with medical staff. DISCUSSION: The results of the study indicate that these families did not get the services they needed. In spite of recounting many system failures, most respondents attributed their situation to tragedy and misfortune at personal and family levels. Such a discourse is closely connected to a wider context of health and social care. The Hong Kong subjects complained more, felt more helpless, and had more persistent self-blame and lay explanation than the Taiwanese subjects. CONCLUSIONS: To reduce such experiences, this paper calls for inclusive policies for the family, new education strategies and reflections on the roles of mental health professionals in empowerment and advocacy beyond conventional treatment, counseling and education. PMID- 17278344 TI - Schneiderian first rank symptoms in a sample of schizophrenic patients in Egypt. AB - BACKGROUND: Schneiderian first rank symptoms are included in the most influential operative diagnostic criteria, such as the ICD-10 and the DSM-IV. Many studies have examined their prevalence in the West, but their prevalence in non-Western countries still needs to be explored given that cultural beliefs are so different. AIMS: The aim of this study is to shed some light on Schneiderian first rank symptoms (FRS) as they occur in patients with schizophrenia in Egypt. METHOD: Forty-two patients were interviewed, their demographic characteristics studied and FRS elicited. The SPSS computer program was used to analyse the data. RESULTS: The prevalence rate of FRS was found to be 67%, which is similar to previous studies both in the East and the West. The study also showed that demographic variables had no significant relation to the prevalence of FRS except for nationality and social status. CONCLUSION: Schneiderian first rank symptoms transcend cultural barriers. However, strong cultural beliefs about the influence of supernatural forces on humans should nonetheless be carefully considered in eliciting delusions of control, influence or passivity. PMID- 17278345 TI - Heavy use of psychiatric inpatient care from the perspective of the patients affected. AB - BACKGROUND: Patients who spend an above-average amount of time in inpatient care are termed heavy users. Up to this point, very little has been known about what drives these patients to their heavy use of inpatient treatment. AIM: For this reason, the present study investigates the causes for frequent inpatient admissions of heavy users from the perspective of the patients affected. METHODS: Twenty heavy users who were identified in a quantitative preliminary study were interviewed using a qualitative analysis of the contents. RESULTS: Heavy users housed in sheltered accommodation either experienced frequent inpatient stays because of their symptomatic burden, or because of poor integration in their residences. Among the heavy users living in private residences was a subgroup that compensated for the lack of support from the private sphere with frequent hospital visits. A second subgroup turned to hospital care only during acute relapse episodes. In a third subgroup, secondary substance abuse accounted for the high demand for inpatient treatment. CONCLUSION: Findings suggest that, using community-based psychiatric support offers tailored to the needs of the heavy user subgroups, inpatient treatment could be avoided. PMID- 17278346 TI - Homeless children and parents: short-term mental health outcome. AB - BACKGROUND: Homeless families are an increasing but marginalised part of society. They have diverse and complex needs that have often not been addressed by the available services. There is some evidence that psychosocial factors continue to be detrimental to the mental health of these families even after rehousing. METHOD: Thirty-five homeless families were assessed on their mental health (Hospital Anxiety and Depression Scale, Eyberg Child Behaviour Inventory Scale, Health of the Nation Outcome Scales for Children and Adolescents), parenting problems (Parenting Daily Hassles Scale), and service satisfaction (semi structured interview) following admission to two homeless hostels, and four months later, when most families (69%) had been rehoused in the community. RESULTS: Children and their mothers continued to experience high rates of mental health problems whilst resident in the hostels and after rehousing. However, a proportion of parents expressed a subjective improvement, which was often associated with their housing and social circumstances. A diverse range of further needs was described. CONCLUSIONS: There is a need to address the complex problems experienced by these families, with housing only forming one aspect of this provision. Interagency strategy, commissioning and services are required to meet the needs of this vulnerable group of parents and children. PMID- 17278347 TI - How social difficulties produce cognitive problems during the mediation of psychosis: a qualitative study. AB - BACKGROUND: The study examines effects of social difficulties such as invalidating and stressful relationships and lack of social support on cognitive processes in psychosis. METHODS: Biographical and ethnographic methods deriving insights from personal experience of psychosis; interactions with patients in hospital and hostel care and from group work. CONCLUSIONS: Social stresses can damage the self, resulting in disarray to executive control, serial ordering, organizational and retrieval processes. Negative social experiences also skew probability judgements of the likelihood of threat/ betrayal which may be confirmed by coincidences--resulting in the adoption of a risky decisional style. This maximizes perceptions confirming of a delusional belief. PMID- 17278348 TI - Family perspective on community treatment orders: a New Zealand study. AB - BACKGROUND: People with serious mental disorders typically live with family members. Despite increasing interest in compulsory community treatment for such patients, the experience and views of their family members have been little studied. MATERIAL: Qualitative interviews with 27 family members, whose relatives have been subject to compulsory community treatment. DISCUSSION AND CONCLUSIONS: Family members are generally in favour of the use of compulsory community treatment orders. They perceive a positive influence on their relative, on themselves, on family relationships, and on relations with the clinical team. Family members are aware of the ethical and other dilemmas that attend the use of compulsory community care. PMID- 17278349 TI - Homelessness and mental illness: a literature review and a qualitative study of perceptions of the adequacy of care. PMID- 17278350 TI - Biological actions of calcium. PMID- 17278351 TI - Professor Ebashi's journey toward the discovery of troponin: a personal recollection. PMID- 17278352 TI - Highlights of the history of calcium regulation of striated muscle. PMID- 17278353 TI - Troponin: structure, function and dysfunction. PMID- 17278354 TI - From the crystal structure of troponin to the mechanism of calcium regulation of muscle contraction. PMID- 17278355 TI - Ca ion and the troponin switch. PMID- 17278356 TI - Disposition and dynamics: interdomain orientations in troponin. PMID- 17278358 TI - Tropomyosin: regulator of actin filaments. PMID- 17278357 TI - Structural basis for calcium-regulated relaxation of striated muscles at interaction sites of troponin with actin and tropomyosin. AB - In summary, we have shown that the TnI-TnC-TnT2 ternary complex (-52 kDa) has a mobile actin-binding domain (-6.1 kDa) that tumbles independently of the core domain. By docking the mobile domain and the core domain into the cryo-EM map obtained for thin filaments at low Ca2+, a model for actin-troponin interaction has been obtained. This model shows the atomic details of interactions of actin with the mobile domain and suggests the mechanism by which troponin generates a shift in the azimuthal position of tropomyosin in response to changes in Ca2+ levels. In this model the mobile domain of troponin interacts with three actins and one troponin interacts with four actin molecules. The relationship between myosin and the mobile domain suggests that the latter may work as a fail-safe latch to secure a relaxed state. The model also provides insights into many mutations associated with human cardiomyopathy and has implications for the function of other actin-binding proteins. Coordinates of the mobile domain have been deposited in the Protein Data Bank under accession codes 1VDI (low Ca2+) and 1VDJ (high Ca2+). Chemical shifts of the mobile domain have been deposited in the BMRB under accession ID 18140. PMID- 17278359 TI - Tropomyosin and troponin cooperativity on the thin filament. PMID- 17278360 TI - Conformational changes in reconstituted skeletal muscle thin filaments observed by fluorescence spectroscopy. PMID- 17278362 TI - Crystal structures of tropomyosin: flexible coiled-coil. AB - Tropomyosin (Tm) is a 400 angstroms long coiled coil protein, and with troponin it regulates contraction in skeletal and cardiac muscles in a [Ca2+]-dependent manner. Tm consists of multiple domains with diverse stabilities in the coiled coil form, thus providing Tm with dynamic flexibility. This flexibility must play important roles in the actin binding and the cooperative transition between the calcium regulated states of the entire muscle thin filament. In order to understand the flexibility of Tm in its entirety, the atomic coordinates of Tm are needed. Here we report the two crystal structures of Tm segments. One is rabbit skeletal muscle alpha-Tm encompassing residues 176-284 with an N-terminal extension of 25 residues from the leucine zipper sequence of GCN4, which includes the region that interacts with the troponin core domain. The other is alpha-Tm encompassing residues 176-273 with N- and C-terminal extensions of the leucine zipper sequences. These two crystal structures imply that this molecule is a flexible coiled coil. First, Tm's are not homogeneous and smooth coiled coils, but instead they undulate, with highly fluctuating local parameters specifying the coiled coil. Independent fluctuating showed by two crystal structures is important. Second, in the first crystal, the coiled coil is bent by 9 degrees in the region centered about Y214-E218-Y221, where the inter-helical distance has its maximum. On the other hand, no bend is observed at the same region in the second crystal even if its inter-helical distance has also its maximum. E218, an unusual negatively charged residue at the a position in the heptad repeat, seems to play the key role in destabilizing the coiled coil with alanine destabilizing clusters. PMID- 17278361 TI - Calcium structural transition of troponin in the complexes, on the thin filament, and in muscle fibres, as studied by site-directed spin-labelling EPR. AB - We have measured the intersite distance, side-chain mobility and orientation of specific site(s) of troponin (Tn) complex on the thin filaments or in muscle fibres as well as in solution by means of site-directed spin labeling electron paramagnetic resonance (SDSL-EPR). We have examined the Ca(2+)-induced movement of the B and C helices relative to the D helix in a human cardiac (hc)TnC monomer state and hcTnC-hcTnI binary complex. An interspin distance between G42C (B helix) and C84 (D helix) was 18.4 angstroms in the absence of Ca2+. The distance between Q58C (C helix) and C84 (D helix) was 18.3 angstroms. Distance changes were observed by the addition of Ca2+ and by the formation of a complex with TnI. Both Ca2+ and TnI are essential for the full opening -3 angstroms of the N-domain in cardiac TnC. We have determined the in situ distances between C35 and C84 by measuring pulsed electron-electron double resonance (PELDOR) spectroscopy. The distances were 26.0 and 27.2 A in the monomer state and in reconstituted fibres, respectively. The addition of Ca2+ decreased the distance to 23.2 angstroms in fibres but only slightly in the monomer state, indicating that Ca2+ binding to the N-lobe of hcTnC induced a larger structural change in muscle fibres than in the monomer state. We also succeeded in synthesizing a new bifunctional spin labels that is firmly fixed on a central E-helix (94C-101C) of skeletal(sk)TnC to examine its orientation in reconstituted muscle fibres. EPR spectrum showed that this helix is disordered with respect to the filament axis. We have studied the calcium structural transition in skTnI and tropomyosin on the filament by SDSL EPR. The spin label at a TnI switch segment (C133) showed three motional states depending on Ca2+ and actin. The data suggested that the TnI switch segment binds to TnC N-lobe in +Ca2+ state, and that in -Ca2+ state it is free in TnC-I-T complex alone while fixed to actin in the reconstituted thin filaments. In contrast, the side chain spin labels along the entire tropomyosin molecule showed no Ca(2+)-induced mobility changes. PMID- 17278363 TI - C. elegans model for studying tropomyosin and troponin regulations of muscle contraction and animal behavior. PMID- 17278364 TI - Structural and functional analysis of troponins from scallop striated and human cardiac muscles. PMID- 17278365 TI - Cooperativity in the regulation of force and the kinetics of force development in heart and skeletal muscles: cross-bridge activation of force. PMID- 17278366 TI - Heart failure, ischemia/reperfusion injury and cardiac troponin. AB - Over the forty years since its discovery, there has been a profound transition in thinking with regard to the role of troponin in the control of cardiac function. This transition involved a change in perception oftroponin as a passive molecular switch responding to membrane controlled fluctuations in cytoplasmic Ca2+ to a perception of troponin as a critical element in signaling cascades that actively engage in control of cardiac function. Evidence demonstrating functionally significant developmental and mutant isoform switches and post-translational modifications of cardiac troponin complex proteins, troponin I (cTnI) and troponin T (cTnT) provided convincing evidence for a more complicated role of troponin in control of cardiac function and dynamics. The physiological role of these modifications of troponin is reviewed in this monograph and has also been reviewed elsewhere (Solaro and Rarick, 1998; Gordon et al., 2000; Solaro et al., 2002a; Kobayashi and Solaro, 2005). Our focus here is on studies related to modifications in troponin that appear important in the processes leading from compensated hypertrophy to heart failure. These studies reveal the potentially significant role of post-translational modifications of troponin in these processes. Another focus is on troponin as a target for inotropic agents. Pharmacological manipulation of troponin by small molecules remains an important avenue of approach for the treatment of acute and chronic heart failure (Kass and Solaro, 2006). PMID- 17278367 TI - Troponin mutations in cardiomyopathies. PMID- 17278368 TI - Molecular pathogenic mechanisms of cardiomyopathies caused by mutations in cardiac troponin T. PMID- 17278369 TI - Cardiac troponin levels as a preferable biomarker of myocardial cell degradation. PMID- 17278370 TI - Regulation by myosin: how calcium regulates some myosins, past and present. PMID- 17278372 TI - Calcium-induced release of calcium from the sarcoplasmic reticulum. PMID- 17278371 TI - Calcium inhibition of Physarum myosin as examined by the recombinant heavy mero myosin. PMID- 17278373 TI - Dysregulation of the gain of CICR through ryanodine receptor1 (RyR1): the putative mechanism underlying malignant hyperthermia. PMID- 17278374 TI - Ion pumping by calcium ATPase of sarcoplasmic reticulum. PMID- 17278375 TI - Regulation of cell functions by Ca2+ oscillation. PMID- 17278376 TI - Evidence about the structural behaviour of myosin crossbridges during muscle contraction. AB - It has been a great honor and a particular pleasure to participate in this meeting to celebrate the fortieth anniversary of the discovery of troponin by Professor Ebashi, whom I have been privileged to know for many years of my scientific life. I thought therefore it would be appropriate to described briefly what was happening in studies of another aspect of muscle contraction over somewhat the same time period. PMID- 17278377 TI - Structural alterations of thin actin filaments in muscle contraction by synchrotron X-ray fiber diffraction. AB - Strong evidence has been accumulated that the conformational changes of the thin actin filaments are occurring and playing an important role in the entire process of muscle contraction. The conformational changes and the mechanical properties of the thin actin filaments we have found by X-ray fiber diffraction on skeletal muscle contraction are explored. Recent studies on the conformational changes of regulatory proteins bound to actin filaments upon activation and in the force generation process are also described. Finally, the roles of structural alterations and dynamics of the actin filaments are discussed in conjunction with the regulation mechanism and the force generation mechanism. PMID- 17278378 TI - Regulation of muscle contraction by Ca2+ and ADP: focusing on the auto oscillation (SPOC). AB - A molecular motor in striated muscle, myosin II, is a non-processive motor that is unable to perform physiological functions as a single molecule and acts as an assembly of molecules. It is widely accepted that a myosin II motor is an independent force generator; the force generated at a steady state is usually considered to be a simple sum of those generated by each motor. This is the case at full activation (pCa < 5 in the presence of MgATP); however, we found that the myosin II motors show cooperative functions, i.e., non-linear auto-oscillation, named SPOC (SPontaneous Oscillatory Contraction), when the activation level is intermediate between those of contraction and relaxation (that is, at the intermediate level of pCa, 5-6, for cardiac muscle, or at the coexistence of MgATP, MgADP and inorganic phosphate (Pi) at higher pCa (> 7) for both skeletal and cardiac muscles). Here, we summarize the characteristics of SPOC phenomena, especially focusing on the physiological significance of SPOC in cardiac muscle. We propose a new concept that the auto-oscillatory property, which is inherent to the contractile system of cardiac muscle, underlies the molecular mechanism of heartbeat. Additionally, we briefly describe the dynamic properties of the thin filaments, i.e., the Ca(2+)-dependent flexibility change of the thin filaments, which may be the basis for the SPOC phenomena. We also describe a newly developed experimental system named "bio-nanomuscle," in which tension is asserted on a single reconstituted thin filament by interacting with crossbridges in the A-band composed of the thick filament lattice. This newly devised hybrid system is expected to fill the gap between the single-molecule level and the muscle system. PMID- 17278379 TI - Muscle contraction mechanism based on actin filament rotation. PMID- 17278380 TI - On the walking mechanism of linear molecular motors. PMID- 17278381 TI - Modeling of the F-actin structure. PMID- 17278382 TI - Lung diseases in South Africa: an overview. AB - The profile of both infectious and non-infectious lung diseases in South Africa over the past century reflects prevailing sociopolitical and economic forces. The lung, perhaps more than any other organ system is influenced by poverty, occupation and personal habits. These influences are seen in the association between tuberculosis and pneumoconiosis first described in miners, the increasing prevalence of asthma and smoking-related chronic obstructive pulmonary disease, and the current dual epidemics of tuberculosis and infections associated with the human immunodeficiency virus (HIV). The global prediction for developing countries is that by the year 2020 respiratory diseases (including infections) will account for a large majority of deaths and a considerable burden of disability adjusted life years. The country-wide Demographic and Health Surveys of 1998 and 2003 have provided data on symptom prevalence in South Africa. The Lung Health Survey 2002 performed in Cape Town provides disease prevalence and has identified complex interactions between causative factors and disease. Consistent and biologically plausible associations between smoking and susceptibility to tuberculosis and pneumonia in HIV-infected patients have been reported. These findings are relevant both to the planners of public health interventions, and to researchers exploring disease mechanisms and potential remedies. PMID- 17278383 TI - TB epidemiology and human genetics. AB - The impact of tuberculosis (TB) is considerably lower than one may expect, since in the absence of immunosuppression, fewer than 10% of infected individuals will develop active disease. The relatively low proportion of individuals who progress to active disease after infection can probably be ascribed to innate resistance in most infected individuals, since vaccination using BCG or a previous episode of TB does not work reliably or effectively to confer protection in high burden parts of the world. Innate factors affecting resistance or susceptibility can be modulated by the environment and such external influences cannot be ignored. Specifically, we will address bacterial variability as well as environmental factors such as diet, smoking, helminths and hormones. We will also discuss host genes that may be involved in susceptibility or resistance at various stages of infection or disease. The discovery of as yet unknown genes impacting on TB susceptibility or disease course may lead to new insights into mechanisms of disease and novel therapies. With adaptive immunity being of little value and good TB control programmes being rare, innate resistance is still our best defence against this PMID- 17278384 TI - Bacterial infections of the lung in normal and immunodeficient patients. AB - The lung is exposed to enormous quantities of air and to potentially infectious agents, but serious infections rarely occur, a testament to the extraordinary natural defences of the respiratory tract. The most common causes of bacterial lung infections in normal hosts include Streptococcus pneumoniae, Haemophilus species, Staphylococcus aureus and Mycobacterium tuberculosis. In compromised hosts, the bacterial causes of pneumonia are much broader, including species not usually considered of high virulence in humans. Indeed infection with one of these unusual bacterial species demands a search for an immunocompromising condition. Normal defences of the respiratory tract include non-specific physical factors (the 'mucociliary escalator'), and innate factors, including defensins, lysozyme and phagocytic cells (polymorphonuclear leukocytes, pulmonary alveolar macrophages and dendritic cells). Antibacterial defences are enhanced by opsonins, including those intrinsically present (surfactant and complement components) and induced immunoglobulins. Immunocompromising conditions, in which bacterial lung infections frequently occur, include (but are not limited to) hypogammaglobulinaemia, chronic granulomatous disease and primary ciliary dyskinesia. Each of these conditions illustrates the essential role of the disabled element of the innate and adaptive immune system in maintaining sterility of the lower respiratory tract. PMID- 17278385 TI - Pathogenesis of avian flu H5N1 and SARS. AB - Avian influenza A (H5N1) and severe acute respiratory syndrome (SARS) coronavirus are infections that cause a severe viral pneumonia leading to acute respiratory dysfunction syndrome and carry a high case-fatality rate. We have investigated innate immune responses to both viruses using primary human macrophages and respiratory epithelial cells as in vitro models. In contrast to human influenza A H1NI viruses, the H5N1 viruses hyper-induce cytokines (tumour necrosis factor [TNF]alpha, interferon beta) and chemokines (IP10, MIP1alpha, MCP) in in vitro cultures of primary human macrophages. A similar differential effect is observed in primary human bronchial epithelial cells and in type 2 pneumocytes although TNFalpha is not induced in respiratory epithelial cells. The cell signalling pathways responsible for this differential effect remain to be explored. Preliminary data suggest that such differential signalling involves p38 MAP kinase rather than NF-kappaB. SARS coronavirus infection of primary human macrophages is associated with a strong induction of chemokines without an associated type 1 interferon response. These observations may be relevant in disease pathogenesis. PMID- 17278386 TI - Immunity and tolerance to Aspergillus fumigatus. AB - The inherent resistance to diseases caused by Aspergillus fumigatus suggests the occurrence of regulatory mechanisms that provide the host with adequate defence without necessarily eliminating the fungus or causing unacceptable levels of host damage. Efficient responses to the fungus require different mechanisms of immunity. Dendritic cells (DCs) are uniquely able to decode the fungus-associated information and translate it into qualitatively different T helper (Th) and regulatory (Treg) cell responses. A division of labour occurred between functionally distinct Treg that were coordinately activated by a CD28/B.7 dependent costimulatory pathway after exposure of mice to Aspergillus conidia. Early in infection, inflammation was controlled by the expansion, activation and local recruitment of CD4+CD25+ Treg capable of suppressing neutrophils through the combined actions of interleukin (IL10) and cytotoxic T lymphocyte antigen 4 (CTLA4) on indoleamine 2,3-dioxygenase (IDO). The levels of IFNgamma produced in this early phase set the subsequent adaptive stage by conditioning the IDO dependent tolerogenic program of DCs and the subsequent activation and expansion of tolerogenic Treg, which produced IL10 and transforming growth factor (TGF)beta, inhibited Th2 cells, and prevented allergy to the fungus. Thus, regulation is an essential component of the host response in infection and allergy to the fungus, and its manipulation may allow the pathogen to overcome host resistance and promote disease. PMID- 17278387 TI - Pentraxins in innate immunity and inflammation. AB - C-reactive protein, the first innate immunity receptor identified, and serum amyloid P component are classic short pentraxins produced in the liver. Long pentraxins, the prototype of which is PTX3, are expressed in a variety of tissues. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to TLR engagement and inflammatory cytokines. PTX3 acts as a functional ancestor of antibodies, recognizing microbes, activating complement, facilitating pathogen recognition by phagocytes, hence playing a non-redundant role in resistance against selected pathogens, in particular in the lung. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor at the crossroads between innate immunity, inflammation, matrix deposition and female fertility. PMID- 17278388 TI - How superoxide production by neutrophil leukocytes kills microbes. AB - Neutrophils represent the primary innate immune response to infection by bacteria and fungi which they ingest, kill and digest. Killing and digestion are dependent upon oxygen consumption by the NADPH oxidase which generates superoxide (O2-) in the phagocytic vacuole. Killing was thought to occur by free radical reactions of reactive oxygen species (ROS) with the microbes, or through the generation of HOCI by myeloperoxidase acting on H2O2. However, in knockout mice lacking the neutral proteases cathepsin G and elastase, these ROS do not kill microbes despite normal production of oxygen free radicals and halogenation. It turns out that the oxidase has another function. The passage of electrons is electrogenic and the charge generated across the wall of the phagocytic vacuole must be compensated if electron transport is to continue. This compensation is largely accomplished by the passage of Cl-, which enters the vacuole from the granules, where it is present at a concentration of about 500mM, into the cytosol. The pH of the vacuole is regulated by a Na+/H+ exchanger, NHE1, which pumps Na+ out of the vacuole in exchange for cytosolic H+ together with a flux of K+ into the vacuole through the BKCa channel. These ion fluxes and pH changes serve to promote microbial killing and digestion by optimizing conditions for the action of the enzymes released from the cytoplasmic granules. PMID- 17278389 TI - Linking innate to adaptive immunity through dendritic cells. AB - The function of dendritic cells (DCs) in linking innate to adaptive immunity is often summarized with two terms. DCs are sentinels, able to capture, process and present antigens and to migrate to lymphoid tissues to select rare, antigen reactive T cell clones. DCs are also sensors, responding to a spectrum of environmental cues by extensive differentiation or maturation. The type of DC and the type of maturation induced by different stimuli influences the immunological outcome, such as the differentiation of Thl vs. Th2 T cells. Here we summarize the contributions of DCs to innate defences, particularly the production of immune enhancing cytokines and the activation of innate lymphocytes. Then we outline three innate features of DCs that influence peripheral tolerance and lead to adaptive immunity: a specialized endocytic system for antigen capture and processing, location and movements in vivo, and maturation in response to an array of stimuli. A new approach to the analysis of DC biology is to target antigens selectively to maturing DCs in vivo. This leads to stronger, more prolonged and broader (many immunogenic peptides) immunity by both T cells and B cells. PMID- 17278390 TI - Macrophage receptors and innate immunity: insights from dectin-1. AB - The innate ability of macrophages to induce an immune response to pathogens is dependent upon germline encoded pattern recognition receptors which recognise conserved microbial structures. These receptors not only mediate pathogen recognition, but promote microbial uptake and killing and the induction of inflammatory responses. Although the recently described Toll-like receptors (TLR) have been shown to play a central role in mediating the intracellular signals involved, the non-TLRs also have important functions in these processes. Once such receptor is Dectin-1, a myeloid expressed signalling C-type lectin-like receptor which is involved in the innate recognition of fungal pathogens. Dectin 1 can induce a variety of cellular responses, including phagocytosis, the respiratory burst and cytokine production. These responses are mediated through novel signalling pathways induced from the cytoplasmic immuno-receptor tyrosine based activation-like motif of the receptor. Although the in vivo role of Dectin 1 has still to be fully elucidated, there is emerging evidence that this receptor plays a role in the inflammatory response to pulmonary fungal pathogens and that it is involved in certain autoimmune and respiratory diseases. PMID- 17278391 TI - Toll-like receptors and control of mycobacterial infection in mice. AB - Microbial products including mycobacterial antigens are recognized by distinct Toll-like receptors (TLRs) resulting in activation of cells of the innate immune system. Ablation of most of the TLR signalling in mice deficient for the common adaptor protein MyD88 revealed that TLRs are crucial for the activation of an innate immune response as MyD88-deficient mice are highly sensitive to infection with Mycobacterium tuberculosis. Despite the profound defect of the innate immune response, MyD88 deficiency allows the emergence of an adaptive immunity. These data demonstrate that activation of multiple TLRs contributes to an efficient innate response to mycobacteria, while MyD88-dependent signalling is dispensable to generate adaptive immunity. PMID- 17278392 TI - Population of lungs by mast cells. AB - Mast cells are tissue-resident cells that are localized particularly in the skin, gastrointestinal tract and respiratory tract. They are mainly recognised for their role in adaptive immunity and allergy where cross-linking of surface-bound IgE results in acute mediator release giving early symptoms, and cytokine production contributing to chronic changes. The mast cell is now also increasingly recognized for its role in innate immunity conferred by its repertoire of complement and Toll receptors. Thus, mast cell deletion has been shown to suppress certain innate immune responses in murine models. Our interest is in the mechanisms involved in population of tissues by mast cells, particularly the airways. Mast cells are released from the bone marrow into the blood as committed precursors. These cells circulate in very low numbers and accumulate in tissues where they proliferate and mature under the influence of local cytokines and growth factors that define the mature phenotype appropriate for their location. Chemoattraction is important at critical phases in the life history of the mast cell, i.e. movement towards and through the bone marrow sinus endothelium, recruitment to tissues and movement within the tissues to the location of the mature cell. These phases are dependent on chemoattractants generated at specific locations acting on cell surface receptors whose repertoire evolves as the mast cell matures. PMID- 17278393 TI - Innate immunity and mucus structure and function. AB - Many of the proteins associated with innate immunity in the upper respiratory tract are to be found localized into mucus gels and the mucin-rich surface layers of the epithelium and the cilia. Mucus is a relatively dilute suspension of such macromolecules being around 2-4% solids in normal induced sputum. These proteins scavenge, immobilise and/or kill pathogens and at the same time immobilize them into the mucus. Mucus is moved from the lung by the mucociliary clearance mechanisms or by cough. Some 190 proteins are readily detectable in sputum by proteomics methods and about 100 in bronchial air-liquid interface culture secretions. This cell culture system mimics the surface ciliated phenotype of the large airways very well and about 85 secreted proteins are common to both culture and sputum secretions. The major single protein by weight in cell culture secretions is MUC5B and in sputum a mixture of MUC5B and MUC5AC. The three epithelial mucins MUC1, 4 and 16 are also detectable in both secretions. In this paper the roles that these molecules play in protecting and stabilising the ciliated surface and building the gel will be discussed. The role of water and ion homeostasis is particularly crucial in mucus gel formation and evidence is gathering that it is perturbation of hydration mechanisms that may play into defective mucus leading subsequently to stasis and mechanical problems. PMID- 17278394 TI - Collectins and host defence. AB - The collectins are a small family of soluble oligomeric proteins containing collagenous regions and C-type lectin domains. They are related in structure and function to complement protein C1q, and to H-, L- and M-ficolins. In humans, the collectins mannose-binding lectin (MBL) and surfactant proteins A and D (SP-A, SP D) have important roles in innate immunity. MBL occurs mainly in blood plasma and in the upper respiratory tract. It binds to neutral sugar arrays on microorganisms and acts as an opsonin either directly (by binding to cell-surface calreticulin) or indirectly by activating complement. MBL circulates in complex with any of three proteases, named MBL-associated serine proteases (MASPs)-1, -2 and -3. MBL-MASP-2 complexes activate complement, but the role of MBL-MASP-1 and MBL-MASP-3 complexes is not yet known. MBL deficiency occurs at high frequency, and is associated with susceptibility to infection, particularly in infants. SP-A and SP-D are most abundant in the lungs, and also bind to microorganisms and inhaled particulates, mainly by lectin-sugar interactions. They do not activate complement, but act as opsonins and agglutinators, and have additional effects on cellular regulation. Mice deficient in SP-A or SP-D are susceptible to lung infections, and SP-D-deficient mice develop an emphysema-like condition. PMID- 17278395 TI - Infections and asthma pathogenesis: a critical role for dendritic cells? AB - Respiratory viral infections can influence the course of asthma at different time points. Severe respiratory viral infections at early age might be associated with a higher prevalence of asthma in later childhood. In established asthma, viral infections are a frequent cause of asthma exacerbation. Epidemiological and experimental animal data can illuminate the mechanisms by which viral infections can lead to sensitization to antigen and exacerbate ongoing allergic airway inflammation. In experimental rodent models of asthma, respiratory viral infection at the time of a first inhaled antigen exposure is described to induce Th2 sensitization and to enhance the allergic response to a second encounter with the same antigen. Virus infections can modulate airway dendritic cell function by up-regulation of costimulatory molecule expression, enhanced recruitment, and by inducing an inflammatory environment, all leading to an enhanced antigen presentation and possibly changing the normal tolerogenic response to inhaled antigen into an immunogenic response. In established asthma, respiratory viral infections attract several inflammatory cells, alter receptor expression on airway smooth muscle and modulate neuroimmune mechanisms, possibly leading to exacerbation of disease. Animal data suggest that the link between respiratory viral infections and increased asthma is causally related, the viral infection acting on the immune and structural cells to enhance antigen presentation and inflammatory cell recruitment. PMID- 17278396 TI - Innate and adaptive immunity in lung cancer. AB - The immune system is alerted to the presence of a pathogen through the activation of the innate immune system. The message is transmitted to the cells of the adaptive immunity through activated antigen-presenting cells. The development of specific immunity capable of eliminating the pathogen is orchestrated by cytokines and chemokines produced by the innate system. When everything functions optimally, the pathogen is eradicated and specific memory response is established. This finely tuned system can be subverted by pathogens, leading to disease. Immunity to cancer is orchestrated in the same way and it is now recognized that the early stages of tumour development are recognized by the cells of innate immunity that transmit this message to the cells of adaptive immunity. The molecules that alert the immune system and are also its targets are tumour antigens. Two important antigens for lung tumour-specific immunity are MUC1 and cyclin B1. We discuss how each molecule interacts with the innate and the adaptive immunity and the types of the immune responses that result for these interactions. We also discuss the state of immunosuppression of adaptive immunity in cancer patients due to chronic activation of the innate immune system. PMID- 17278397 TI - Update on Crawford v. Washington. PMID- 17278398 TI - Crisis in access to care: geriatric psychiatry services unobtainable at any price. PMID- 17278399 TI - An occupational health services initiative at a women's hospital in Kabul, Afghanistan. AB - This article describes the process of developing targeted occupational health services for the health care workers in a women's hospital in Kabul, Afghanistan, as part of a larger project to establish an obstetrics and gynecology residency training program at the facility. The goal was to create a feasible and sustainable program to: (1) address basic health care needs impacting the ability of these Afghan health care workers to optimize learning opportunities; (2) decrease absenteeism due to illness; (3) decrease the likelihood of infectious disease transmission among staff, from staff to patients, and from patients to staff; (4) foster belief that a healthy and safe working environment is a basic right; (5) begin to collect preliminary health status indicators on health care workers in this employee population; and (6) serve as an adaptable program to expand to other Afghan health care workers. PMID- 17278400 TI - Outbreak bias in illness reporting and case confirmation in ciguatera fish poisoning surveillance in south Florida. AB - OBJECTIVE: Ciguatera fish poisoning is a potentially life-threatening disease caused by eating coral reef fish contaminated with ciguatoxins and is the most common marine poisoning. However, existing surveillance systems capture few cases. To improve regional ciguatera surveillance in South Florida, this study compared ciguatera illnesses in the Florida Poison Information Center-Miami (FPICM) call database to ciguatera cases in the Florida Department of Health (FDOH) disease surveillance systems. METHODS: Univariate and multivariate logistic regression were used to identify predictors of when FPICM reported ciguatera illnesses to FDOH and whether FDOH confirmed reported ciguatera cases. RESULTS: FPICM staff preferentially reported ciguatera illnesses that were of shorter duration (adjusted odds ratio [AOR] = 0.84 per additional illness day; 95% confidence interval [CI] 0.74, 0.97); outbreak-associated (AOR = 7.0; 95% CI 2.5, 19.5); and clinically more severe (AOR = 21.6; 95% CI 2.3, 198.5). Among ciguatera illnesses reported to FDOH, outbreak-associated illnesses were more likely than single, sporadic illnesses to become confirmed surveillance cases (crude OR = 11.1; 95% CI 2.0, 62.5). CONCLUSIONS: The over-representation of outbreak-associated ciguatera cases underestimates the true contribution of sporadic illnesses to ciguatera disease burden. This bias should be considered when evaluating surveillance systems that include both outbreak-associated and sporadic illness reports. PMID- 17278401 TI - Relating West Nile virus case fatality rates to demographic and surveillance variables. AB - OBJECTIVE: The purpose of this ecological study was to relate West Nile virus (WNV) human case fatality rates to county-level demographic and surveillance variables, thereby characterizing the populations to which WNV poses the greatest threat. METHODS: The authors acquired data on human, avian, and mosquito WNV infections for the 13 states in which there were 100 or more human cases during 2003. The data on avian and mosquito infections were converted into surveillance variables using empirical Bayes methodology. A preliminary logistic regression model was formulated to relate these surveillance variables and demographic variables to case fatality rates. The statistical technique of backward elimination was applied to obtain a final model in terms of the variables most useful for predicting case outcomes. RESULTS: The probability of a fatal outcome depends on the poverty rate for the county in which the infected person lives (p = 0.0283), the average temperature (p < 0.0001), and surveillance variables reflecting the fractions of Culex pipiens and Culex restuans mosquitoes among infected mosquitoes (p = 0.0079; p = 0.0076). CONCLUSIONS: Effective WNV educational programs and control measures are vital, especially in poverty stricken areas. A uniform protocol for disseminating county-level data could facilitate timely responses to WNV outbreaks and to emerging infectious diseases more generally. PMID- 17278403 TI - Preventing influenza: vaccine systems and practices in the Southeast. AB - OBJECTIVES: The purpose of this study was to determine from state and local health departments: (1) how they purchase, distribute, and fund influenza vaccine; (2) whether they experienced a shortage in 2003/04; (3) how the shortages were handled; and (4) how they prepared for distribution in 2004/05. METHODS: A web-based survey was completed from June to August 2004 in eight Southeastern states. RESULTS: Data were obtained from each state and 222 local health departments. Major differences between and within states were found with regard to purchasing, distributing, and funding influenza vaccine. Although the majority of health departments experienced periods of shortages in 2003/2004, surpluses of vaccine remained at the end of the season. There was little evidence of interaction between the public and private sectors to share vaccine resources in response to shortages. Tracking systems for redistribution of vaccine or follow-up were often not in place. Entering the 2004/05 season, 25% of states and 11% of counties were not developing any special procedures to deal with shortages beyond what was in place earlier. CONCLUSIONS: Better systems and funding are needed, especially for adult influenza vaccine delivery and for redistribution of influenza vaccine in response to shortages. PMID- 17278402 TI - Infectious disease hospitalizations among older American Indian and Alaska Native adults. AB - OBJECTIVES: American Indians and Alaska Natives (AI/AN) adults > or = 65 years of age (older adults) have the second highest age group-specific infectious disease (ID) hospitalization rate. To assess morbidity and disparities of IDs for older AI/AN adults, this study examined the epidemiology of overall and specific infectious disease hospitalizations among older AI/AN adults. METHODS: ID hospitalization data for older AI/AN adults were analyzed by using Indian Health Service hospital discharge data for 1990 through 2002 and comparing it with published findings for the general U.S. population of older adults. RESULTS: ID hospitalizations accounted for 23% of all hospitalizations among older AI/AN adults. The average annual ID hospitalization rate increased 5% for 1990-1992 to 2000-2002; however, the rate increased more than 20% in the Alaska and the Southwest regions. The rate for older AI/AN adults living in the Southwest region was greater than that for the older U.S. adult population. For 2000-2002, lower respiratory tract infections accounted for almost half of all ID hospitalizations followed by kidney, urinary tract, and bladder infections, and cellulitis. CONCLUSIONS: The ID hospitalization rate increased among older AI/AN adults living in the Southwest and Alaska regions, and the rate for the older AI/AN adults living in the Southwest region was higher than that for the U.S. general population. Prevention measures should focus on ways to reduce ID hospitalizations among older AI/AN adults, particularly those living in the Southwest and Alaska regions. PMID- 17278404 TI - Can data from programs for the prevention of mother-to-child transmission of HIV be used for HIV surveillance in Kenya? AB - OBJECTIVE: In Africa, HIV surveillance is conducted among antenatal clinic (ANC) attendees using unlinked-anonymous testing (UAT). In Kenya, the utility of prevention of mother-to-child transmission (PMTCT) program data for HIV surveillance was evaluated. METHODS: UAT and PMTCT data were compared at the same clinics and for the same time (2003 UAT survey) period. The HIV testing uptake for PMTCT was defined as the number of ANC attendees tested for HIV out of those who had their first ANC visit during the ANC surveillance period. Odds ratios and 95% confidence intervals were calculated to determine associations between demographic characteristics and HIV testing acceptance. RESULTS: Of 39 ANC-UAT sites, six had PMTCT data. PMTCT data were recorded across several logbooks with varying quality. For PMTCT, 2,239 women were offered HIV testing and 1,258 (56%) accepted; for UAT, 1,852 women were sampled. Median UAT-based HIV prevalence was 12.8% (range, 8.1%-26.3%) compared with 14.4% (range, 7.0%-27.2%) in PMTCT. HIV testing acceptance for PMTCT ranged from 48% to 69% across clinics, and was more likely among primigravidae than multigravidae. CONCLUSION: Because of varying PMTCT data quality and varying HIV testing acceptance for PMTCT, PMTCT-based HIV prevalence estimates cannot currently replace UAT-based estimates in Kenya. PMID- 17278405 TI - The effect of message type on physician compliance with disease reporting requirements. AB - OBJECTIVE: Despite the existence of mandatory reporting laws, the underreporting of disease conditions to public health authorities is widespread. This article describes an evaluation of the effects of using different appeals to promote complete and timely reporting to the New York State Occupational Lung Disease Registry (NYS OLDR). METHODS: Three-hundred sixty-eight physicians who had not reported patients were randomly assigned to receive correspondence emphasizing either the legal obligation to report, the public health benefits of reporting, or both. Chi-square tests were used to determine if the proportion of physicians who subsequently reported patients differed by message group. Chi-square tests and the Kruskall Wallis rank sum test were used to test for differences in the completeness and timeliness of reports received from physicians in the three message groups. RESULTS: Physicians receiving correspondence describing the legal obligation to report were more likely to report patients than those receiving only the benefit message, while those receiving correspondence describing the public health benefits of reporting submitted more complete reports than those receiving only the obligation message. CONCLUSIONS: To maximize physician reporting, it is important for public health agencies to emphasize both the legal and public health basis for reporting conditions in correspondence to physicians. PMID- 17278406 TI - Self-reported hepatitis C virus antibody status and risk behavior in young injectors. AB - OBJECTIVE: This study was conducted to assess the accuracy of self-reported hepatitis C virus (HCV) antibody (anti-HCV) serostatus in injection drug users (IDUs), and examine whether self-reported anti-HCV serostatus was associated with recent injection risk behavior. METHODS: In five U.S. cities (Baltimore, Chicago, Los Angeles, New York, and Seattle), 3,004 IDUs from 15 to 30 years old were recruited for a baseline interview to determine eligibility for a randomized controlled trial of a behavioral intervention. HIV and HCV antibody testing were performed, and subject data (e.g., demographics, drug and sexual risk behavior, and history of HIV and HCV testing) were collected via audio computer administered self-interview. Risk behavior during the previous three months was compared to self-reported anti-HCV serostatus. RESULTS: Anti-HCV prevalence in this sample of young IDUs was 34.1%. Seventy-two percent of anti-HCV-positive and 46% of anti-HCV-negative IDUs in this sample were not aware of their HCV serostatus. Drug treatment or needle exchange use was associated with increased awareness of HCV serostatus. Anti-HCV-negative IDUs who knew their serostatus were less likely than those unaware of their status to inject with a syringe used by another IDU or to share cottons to filter drug solutions. Knowledge of one's positive anti-HCV status was not associated with safer injection practices. CONCLUSIONS: Few anti-HCV-positive IDUs in this study were aware of their serostatus. Expanded availability of HCV screening with high quality counseling is clearly needed for this population to promote the health of chronically HCV infected IDUs and to decrease risk among injectors susceptible to acquiring or transmitting HCV. PMID- 17278408 TI - Inadequate prenatal care and elevated blood lead levels among children born in Providence, Rhode Island: a population-based study. AB - OBJECTIVE: This study was conducted to determine whether children born to mothers receiving inadequate prenatal care are at an increased risk for having an elevated blood lead level during early childhood. METHODS: The authors conducted a population-based study of children born in Providence, Rhode Island, from 1997 to 2001 whose mothers had received adequate, intermediate, or inadequate prenatal care. The children's blood lead levels were compared between groups using bivariate and logistic regression. To understand the regulatory implications and public health impact of changing the definition of an elevated blood lead level, "elevated" was defined as 5 microg/dL, 10 microg/dL, and 15 microg/dL. RESULTS: Children born to mothers who received inadequate prenatal care were at an elevated risk for having an elevated blood lead level later in life. This relationship remained statistically significant for each definition of elevated blood lead level and after controlling for other socio-economic status measures and birthweight (at 5 microg/dL, odds ratio [OR] = 1.36, 95% confidence interval [CI] 1.09, 1.68, p = 0.006; at 10 microg/dL, OR = 1.68, 95% CI 1.26, 2.24, p < 0.0004; at 15 microg/dL, OR = 1.83, 95% CI 1.10, 3.04, p = 0.019) represent an opportune moment to identify expectant mothers living in lead-contaminated environments. CONCLUSIONS: Results suggest that conducting lead screening as a regular part of prenatal care provision could help identify women possibly experiencing ongoing lead exposure and help reduce or prevent exposures to their offspring. PMID- 17278409 TI - A state-based analysis of public health preparedness programs in the United States. AB - OBJECTIVES: Given the national effort to respond to the challenge of terrorism post-9/11, this study examined the organizational structure of state public health preparedness programs across the country, their administration, and the personnel and resources supported through federal cooperative agreements and state funds. METHODS: In Fall 2004, the Association of State and Territorial Health Officials surveyed state public health preparedness directors of all 50 states and territories of the United States regarding the organizational structure, administration, personnel, and resources of the state public health preparedness programs. RESULTS: Individuals representing 45 states and the District of Columbia responded to the web-based questionnaire for a response rate of 88.2%, States tended to subdivide their organizations into regions for preparedness purposes. More than half the established preparedness regions (53.8%) were created post-9/11. Preparedness program directors frequently reported directly to either the state health official (40.0%) or a deputy state health official (33.3%). Responsibility for both the Centers for Disease Control and Prevention (CDC) and Health Resources and Services Administration (HRSA) cooperative agreements was predominantly vested in one person (73.3%). Federal resources were found to support needed preparedness workforce (CDC mean = 117.1 full-time equivalents [FTEs]; HRSA mean = 10.6 FTEs). In addition, 36.6% of the states also contributed to the public health preparedness budget. CONCLUSIONS: This study of state public health agency preparedness provides new information about state-level organizational structure, administration, and support of preparedness programs. It offers the first comprehensive insights into the approaches states have adopted to build infrastructure and develop capacity through CDC and HRSA funding streams. PMID- 17278407 TI - The association between childhood asthma and community violence, Los Angeles County, 2000. AB - OBJECTIVE: This study's objective is to determine if there is an association between rates of violence and rates of childhood asthma in Los Angeles County communities. METHODS: Rates of hospitalization for assault and for asthma were calculated for each ZIP Code and city in Los Angeles County. Linear regression was used to determine the effect of assault rates on asthma rates while controlling for potential confounders such as poverty and racial/ethnic distribution. At the city level, crime rates were included in the model as additional measures of community violence. RESULTS: Hospitalization rates for childhood asthma and assaults were significantly correlated at both the city (r = 0.80) and the ZIP Code (r = 0.54) levels. The association remained significant when controlling for poverty and racial/ethnic distribution with linear regression (p < 0.0001). At the city level, the variables measuring the crime rate were not significant predictors of asthma hospitalizations. CONCLUSIONS: Community violence as measured by the rate of assault hospi; talizations is associated with childhood asthma in Los Angeles County. Health care providers should consider their asthmatic patients' social environments when devising treatment plans. PMID- 17278410 TI - The contribution of specific causes of death to sex differences in mortality. AB - OBJECTIVE: Men have higher mortality rates than women for most causes of death. This study was conducted to determine the contribution of specific causes of death to the sex difference in years of potential life lost (YPLL). METHODS: The authors examined data from the National Health Interview Survey with linked mortality data through 1997. Using survival analysis estimates, a stochastic simulation model to simulate death events for cohorts of white, African American, and Latino adults was created. RESULTS: YPLL from all causes were greater among men than women. Homicide, motor vehicle accidents, and suicide accounted for 33% of YPLL sex difference among whites, 36% among African Americans, and 52% among Latinos. For all three racial/ethnic groups, cardiovascular disease (principally ischemic heart disease) was the second largest contributor to the sex difference in YPLL (29% among whites, 23% among African Americans, and 25% among Latinos). Lung cancer was also important among whites and African Americans, accounting for 15% and 17% of the sex difference in YPLL from all causes, respectively. CONCLUSIONS: Ischemic heart disease, lung cancer, and traumatic deaths account for as much as three-quarters of the excess YPLL among men, suggesting that a few modifiable behaviors such as the use of tobacco, alcohol. PMID- 17278412 TI - Financing health care for the poor in Turkey: is a temporary solution becoming a permanent scheme? PMID- 17278411 TI - Smoking prevalence among asian americans: findings from the National Latino and Asian American Study (NLAAS). AB - OBJECTIVE: National studies suggest that the prevalence of current smoking among Asian Americans is lower than that for other racial/ethnic groups. However, these studies may have yielded inaccurate estimates because of the underrepresentation of non-English-speaking groups. Using data from the National Latino and Asian American Study (NLAAS), the authors estimated the prevalence of current and lifetime smoking among Asian Americans. METHODS: Current and lifetime smoking status was assessed through a population-based survey administered to Asian American adults aged 18 and older. RESULTS: An overall current smoking prevalence of 14.9% was found, with notable differences by gender, nativity, and other sociodemographic factors. The prevalence of current smoking was higher among foreign-born vs. U.S.-born men (24.9% vs. 15.6%), while U.S.-born women had a higher prevalence than foreign-born women (6.3% vs. 11.7%). Overall, 28.3% of Asian Americans were ever smokers (including current and former smokers), suggesting that approximately half of ever smokers cease smoking. Results indicated that some Asian American groups are more likely to initiate smoking and/or be more likely to continue smoking. CONCLUSION: Results revealed that the prevalence of current smoking exceeds that of the general U.S. population for some Asian American groups and suggest that excluding non-English-speaking Asian Americans may underestimate the prevalence of smoking among men. Findings indicate that some Asian American groups are at greater risk for initiating smoking and/or continuing smoking, and highlight the need for tailored interventions that address differential smoking patterns by gender, nativity, and other social characteristics. PMID- 17278413 TI - When public health meets market forces: Rapanos v U.S. Army Corps of Engineers. PMID- 17278414 TI - Urban evacuations and rural America: lessons learned from Hurricane Rita. PMID- 17278415 TI - Exoneration reduces adult conflict's effects on preschoolers' cognitions, behavioral distress, and physiology. AB - In this experiment, the authors investigated the influence of exoneration from blame on children's overt behavioral distress and physiological reactivity following the presentation of overheard adult conflict. The participants were 48 children (48-71 months of age) and their mothers. Through random assignment, the authors presented 16 children with statements that exonerated them from an overheard disagreement between two adults, did not address 16 during a similar disagreement, and presented 16 with a neutral discussion of difficulties. Exonerated children responded with less distress than did nonaddressed children, but did not differ from children presented the neutral discussion, except for overt behavioral distress. Nonaddressed children most often blamed themselves for the argument. Exonerating statements may protect children from attributional error and resultant physiological arousal during adult conflict. PMID- 17278416 TI - The frontal hypothesis of cognitive aging: factor structure and age effects on four frontal tests among healthy individuals. AB - With 101 healthy aging adult participants, the authors investigated whether executive functions are a unitary concept. The authors established the factor structure of the Wisconsin Card Sorting Test (WCST; E. A. Berg, 1948), the Stroop color and word test (C. J. Golden, 1978), verbal fluency using the Controlled Oral Word Association Test (COWAT; Benton, 1967), and the Digits Backwards subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R; D. Wechsler, 1981). The authors also evaluated the extent to which age and other demographic variables predicted common underlying properties of these frontal tests. Results revealed an age-related decline in executive abilities differentially reflected by the selected tasks. These data suggest caution using the COWAT to evaluate executive abilities in older people. The authors interpret findings to support the unitary view of executive abilities and the executive decline proposed by the frontal hypothesis. PMID- 17278417 TI - Younger children's changing self-concepts: boys and girls from preschool through second grade. AB - The author investigated age- and gender-related changes in self-evaluative judgments of 87 children followed from preschool through 2nd grade. Focusing on cognitive, physical, and peer competence assessed by the Pictorial Scale of Perceived Competence and Social Acceptance (PSPCSA; S. Harter & R. Pike, 1984), the author tested PSPCSA subscale measures for changes in their mean levels, for intercorrelations, and for correlations with external criteria, and then analyzed results for gender and grade trends. Gender effects were not identified in the analyses. Mean-level changes occurred, but patterns of change differed. External measures (teacher ratings) did not relate to children's self-perceptions (physical and social competences). Whereas external measures of academic competence correlated significantly with children's self-evaluations, the correlations across grade levels did not differ significantly. PMID- 17278418 TI - Adult age, gender, and race group differences in images of aging. AB - Younger and older African American and Caucasian American adults, who were matched by age (M age = 40.63 years), completed a survey on perceptions of aging and subjective age. The 2 groups did not differ in the age they considered someone to be old (M age = 74.5 years). However, when asked which age was the happiest age, African Americans chose a significantly younger age (M age = 18.26 years) than did Caucasian Americans (M age = 31.32 years), and this racial group difference interacted with age differences such that older Caucasian Americans named an older age than did younger Caucasian Americans. The authors found no such age difference for African Americans. When asked if old age was a happy time, 60% of Caucasian Americans answered yes, whereas only 2% of African Americans answered yes. These and other differences in images and concerns of old age and subjective age suggest a far more negative view of aging for African Americans and a need for changes in the provision of positive information about aging for this group. PMID- 17278419 TI - Differentiation at higher levels of cognitive ability: evidence from the United States. AB - Most psychologists and educators assume that intelligence is a linear construct, meaning that smart people simply have more intelligence than their less gifted peers. Likewise, individuals with mental retardation are thought to have less intelligence. In contrast to this widely accepted belief, the authors posed an alternative hypothesis--that intelligence is qualitatively different in various populations. Using factor analysis of a standardization sample of the Woodcock Johnson Test of Cognitive Ability (R. W. Woodcock & M. B. Johnson, 1989), the authors examined the nature of intellect across ability. Results indicated that the amount of variance attributable to Spearman's g declined as measured intellectual ability increased. PMID- 17278420 TI - [Development of optimized combination and clinical application of thrombosis and hemostasis experimental study]. PMID- 17278421 TI - [Antithrombotic mechanisms of holothurian glycosaminoglycan extracted from sea cucumber]. AB - OBJECTIVE: To investigate the antithrombotic mechanisms of holothurian glycosaminoglycan (GAG) extracted from sea cucumber. METHODS: Human endothelial cell line EA. hy926 cells were treated with 10 mg/L GAG or 10U/mL unfractionated heparin (UFH) by short-term (15 min - 2 h) and longer-time incubation (6 h - 48 h). Different doses of GAG were used to stimulate EA. hy926. Released free tissue factor pathway inhibitor(TFPI) was determined by ELISA assay. TFPI expression was investigated by immunofluorescent method and TFPI mRNA level by real-time PCR. In a 96-wells microtitre plate, pooled normal plasma containing different concentrations of GAG was allowed to clot by addition of thrombin and calcium chloride, fibrinolysis was induced by addition of t-PA. TRR (TAFI-related retardation of clot lysis) was used to assess thrombin-activatable fibrinolysis inhibitor(TAFI) functional activity. RESULTS: GAG increased TFPI synthesis, expression and secretion in a dose- and time dependent manner. GAG at low concentrations could lengthen while at intermediate concentrations could shorten clot lysis times significantly as compared to control values. TRR was dose dependently decreased on addition of GAG. CONCLUSIONS: GAG increases TFPI synthesis, expression and secretion of endothelial cells. GAG at intermediate concentrations significantly affects clot stability of a developing clot by means of diminishing TAFI activation. PMID- 17278422 TI - [A preliminary study of an inherited macrothrombocytopenia disorder with abnormal large granules]. AB - OBJECTIVE: To study the platelet morphology and function of an inherited macrothrombocytopenia disorder with abnormal large granules. METHODS: Platelet size and structure were investigated by both light microscopy and electron microscopy. The platelet membrane expression of GP I b, GP II b, GPIII a, P selectin and CD63 were analyzed by using respective monoclonal antibodies. Platelet 5-hydroxy-tryptamine was measured with spectrophotofluorometer. RESULTS: Both the patient and her father had large granules in their platelets, with exocytosis being easily observed. The expressions of GP I b, GP II b and GP II a on the platelets were in normal range, while P-selectin and CD63 were somewhat increased. The abnormal large granules were not the alpha granules, lysosomes or dense bodies. CONCLUSION: Both morphological and functional abnormalities of the platelets from the patient are clearly distinguishable from other hereditary giant platelet disorders. It would probably represent a novel platelet disorder. PMID- 17278423 TI - [The fibrinolytic activity in leukemic cell lines and its alteration on all-trans retinoic acid treatment]. AB - OBJECTIVES: To study the fibrinolytic activity and the expression of uPAR and Annexin II in leukemic cell lines and their alterations on all-trans retinoic acid ( ATRA) treatment. METHODS: The fibrinolytic activity was measured by chromogenic assay in NB4, SHI-1, K562, Jurkat and Raji cell lines. The protein expression of uPAR and Annexin II on cells surface and the mRNA expression of uPAR and Annexin II in cells of these cell lines were detected using flow cytometry and RT-PCR method respectively. RESULTS: The plasmin activity in supernatant was increased significantly after incubation of SHI-1 and NB4 cells with plasminogen. The plasmin activity of NB4 cells was obviously decreased by ATRA. The plasmin activity of NB4 and SHI-1 cells was significantly decreased by uPAR monoclonal antibodies. The expressions of uPAR and Annexin II and their mRNA in SHI-1 and NB4 cells were higher than that in other cell lines. ATRA could remarkably decrease the expressions of Annexin II and uPAR and their mRNA in NB4 cells. CONCLUSION: In leukemia cell lines, NB4 and SHI-1 cells have stronger fibrinolytic activity. Both Annexin II and uPAR on the leukemic cell membranes might contribute to this activity. The high fibrinolytic activity can be corrected by ATRA by down-regulating Annexin I and uPAR mRNA and protein expression in NB4 cells. PMID- 17278424 TI - [Identification of IgG subclass and FVIII binding epitope of an acquired FVIII inhibitor in a bullous pemphigoid patient]. AB - OBJECTIVE: To identify the clinical and laboratory diagnosis of a bullous pemphigoid patient with acquired hemophilia A (AH-A). To identify FVIII binding epitope and IgG subclass of the FVIII inhibitor, and explore the molecular mechanism for AH-A pathogenesis. METHODS: Plasma FVIII activity( FVIII: C) was determined by one-stage assay, the titre of FYIII inhibitor by Bethesda Unit (BU). IgG purification of patient plasma or normal pooled plasma was finished by protein A-agarose column chromatography. Activated partial thromboplastin time (APTT) was assayed for uncovering FVIII inhibitor effect on FVIII in vivo. Combined Western blot analysis by anti-IgG1, IgG2, IgG3 and IgG4 antibodies was used to determine the relative concentration of patient' s IgG subclass. IgG subclass concentrations were quantified by nephelometric method. Solid-phase binding assay of FVIII and FVIII inhibitor, combined with Western blot was used to recognize the binding epitope at which the FVIII inhibitor bound to FVIII. RESULTS: (1) Plasma APTT value of patient was prolonged evidently and could not be corrected by normal pooled plasma. Patient's FVIII: C was < 1.5%. The titre of FVIII inhibitor in patient plasma was 147.8 BU. (2) The purified patient IgG was able to inhibit FVIII: C of normal pooled plasma significantly with a dose dependent manner, and the patient plasma could prolong rabbit plasma APTT markedly with a time dependent manner. (3) The FVIII inhibitor was predominantly then of IgG4 subtype with a minority IgG1, and the concentration of IgG4 and IgG1 in the patient was higher than that in normal. The FVIII inhibitor reacted with FVIII 44 x 10(3) fragment epitope. CONCLUSIONS: The inhibiting effect of FVIII inhibitors on FVIII: C in the bullous pemphigoid patient with AH-A is determined and the IgG subclass of the FVIII inhibitor is identified. A binding epitope for the FVIII inhibitor is a FVIII 44 x 10(3) fragment. The results provides evidence for understanding the pathogenesis of AH-A. PMID- 17278426 TI - [Cloning and functional analysis of P2X7 receptor from J6-1 leukemia cells]. AB - OBJECTIVE: To clone the entire coding sequence and analyze the function of P2X7 receptor of J6-1 human leukemia cells. METHODS: The entire coding sequence of P2X7 receptor was amplified by RT-PCR and then inserted into pTARGET plasmid to construct an eukaryotic expressing plasmid followed by DNA sequencing. HEK293 cells stably expressing P2X7 receptor were obtained after transfection and screening, and confirmed by RT-PCR and Western blotting. The bleb formation upon agonist stimulation was observed under phase contrast microscope. RESULTS: The entire coding sequence of P2X7 receptor of J6-1 cells was successfully cloned. DNA sequencing analysis revealed a substitution of G559, for A559, causing a substitution of Glu187 for Gln187. The P2X7 receptor derived from J6-1 cells could be functionally expressed in HEK293 cells, in which bleb formation could be detected upon stimulation. CONCLUSIONS: The entire coding sequence of P2X7 receptors was successfully cloned from J6-1 leukemia cells. Other unknown mechanism may contribute to the dysfunction of P2X7 receptor in these cells. PMID- 17278425 TI - [A novel mutation in antithrombin gene results in hereditary antithrombin deficiency]. AB - OBJECTIVE: To investigate the antithrombin (AT) activity (AT: A) and AT antigen (AT: Ag) level in a Chinese family with type I antithrombin (AT) deficiency, and to explore the molecular mechanism of AT deficiency. METHODS: Immuno-nephelometry and chromogenic assay were used to detect the plasma level of AT: A and AT: Ag, respectively. Genomic DNA was isolated from the peripheral blood, and all the seven exons and exon-intron boundaries of AT gene were amplified by PCR and direct sequencing. RESULTS: The plasma levels of AT: A and AT: Ag of the proband were 45% and 97 mg/L, respectively, which led to a type I AT deficiency. A heterozygous T to A mutation was found at nucleotide 9833 in exon 5 resulting in a Tyr363Stop nonsense mutation. The sequencing results from the pedigree indicated that four other members also had this mutation. CONCLUSION: This heterozygous nonsense mutation of T9833A in exon 5 resulting in venous thrombosis is a novel genetic defect of hereditary AT deficiency, which has not been described before. PMID- 17278427 TI - [Cloning, expression and biological characterization of hTFPI-2 gene]. AB - OBJECTIVE: To clone the human tissue factor pathway inhibitor-2 (hTFPI-2) gene and express it by using prokaryotic expression system. METHODS: The hTFPI-2 coding region was obtained by RT-PCR from human placenta total RNA. The coding fragment was then inserted into prokaryotic expression vector pET19b and expressed in E. coli BL21 by IPTG induction. The produced inclusion bodies were dissolved by denaturalizing chemicals, purified by ion exchange chromatograph, and refolded in air to form proper disulfide bonds. Chromogenic and gelatin zymography methods were used to evaluate the inhibiting effects of hTFPI-2 on trypsin, plasmin and MMPs individually. The inhibitory activity of hTFPI-2 on fabrisarcoma was investigated by matrigel. RESULTS: The coding fragment of hTFPI 2 was cloned successfully and the protein was expressed as inclusion bodies which account for 20% - 30% of total host protein. The refolded hTFPI-2 could inhibit the invasive ability of fibrisarcoma HT-1080 as well as activity of plasmin, trypsin and MMPs. CONCLUSIONS: The activated hTFPI-2 is obtained by using prokaryotic expressed system effectively. PMID- 17278428 TI - [Study on the peripheral blood dendritic cells subtypes and the expression of co stimulating molecules on dendritic cells and B cells in severe aplastic anemia patients]. AB - OBJECTIVE: To investigate the quantities of monocyte-derived dendritic cell precursors (pDC1) and plasmacytoid dendritic cell precursors (pDC2) in peripheral blood mononuclear cells (PBMC) of severe aplastic anemia (SAA) patients before and after immune suppressive therapy (IST), the ratio of the pDC1 to pDC2, and the expression of co-stimulating molecules (CD80, CD86, CD40) on dendritic cells (DC) and B cells in SAA patients. METHODS: By means of three color monoclonal antibody labeling technology, the quantities and ratio of pDC1 and pDC2 in PBMC were detected in 26 SAA patients at active phase, 13 at recovery phase and 15 normal controls respectively. The aforementioned parameters of 10 SAA patients were tested before and 2 months after IST. The expression of CD80, CD86 and CD40 on DC and B lymphocytes were detected in 16 SAA patients and 15 normal controls. RESULTS: The percentages of pDC1 and the ratio of pDC1/pDC2 of controls were (0.41 +/- 0.05)% and 1.58 +/- 0.18 respectively, and those of SAA patients at active phase were (0.67 +/- 0.13)% and 2.70 +/- 0.32 respectively, [pDC1 (P < 0.05); pDC1/ pDC2 ratio (P < 0.01)]. The aforementioned parameters in convalescent SAA patients decreased to (0.43 +/- 0.10)%, and 1.78 +/- 0.36 respectively, being no difference from those of normal controls. The percentages of pDC1 and pDC2 in 10 SAA patients were (0.87 +/- 0.31)%, and (0.35 +/- 0.09)%, before IST, and (0.24 +/- 0.09)%, (0.14 +/- 0.04)%, after IST, being significantly decreased (P < 0.05). The percentages of CD86 expression on DC of controls was (11.97 +/- 4.31)%, and that of SAA patients was (29.84 +/- 3.02) % (P < 0.05). The percentages of CD80, CD40 and CD86 expression on lymphocytes of controls were (2.57 +/- 0.44)%, (7.34 +/- 1.22)% and (1.86 +/- 1.11)%, respectively, and those of SAA patients were (5.17 +/- 0.68)%, (8.85 +/- 2.94)% and (5.98 +/- 0.96)% respectively (P < 0.05, P < 0.01). The percentage of CD86 expression on B lymphocytes in controls was 8.04 +/- 0.66%, and in SAA patients was (20.46 +/- 2.78)%, (P < 0.05). CONCLUSION: The pDC subtypes were abnormal and the percentage of pDC1 is increased in SAA patients, which are associated with stage of this disease. DC and B Lymphocytes in SAA patients upregulated expression of costimulatory molecules (CD86) which cause the T lymphocyte abnormally activated. PMID- 17278430 TI - [Study of clinical outcome and analysis of prognosis related factor in children with acute myeloid leukemia]. AB - OBJECTIVE: To analyse the clinical outcome and the prognostic factor of childhood acute myeloid leukemia (AML). METHODS: Disease-free survival (DFS), event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method and prognostic factors were evaluated by Cox regression with SPSS in 141 childhood AML in our hospital from August 1995 to July 2004. The patients were divided into 2 groups: acute promyelocytic leukemia (APL) as group A and AML other than APL as group B. RESULTS: Of the 90 group B patients, 54.4% (49/90) achieved complete remission (CR) after one course chemotherapy , with a total CR rate of 76.7%. The cumulative 5 year DFS and OS rate for group B patients were (28.4 +/- 9.0)% and (35.5 +/- 6.3)%, the 51 group A patients were (94.3 +/- 4.0)% and (81.4 +/- 5.7)%, and for total 141 AML patients were (56.9 +/- 6.3)% and (53.3 +/- 4.8)% respectively. Multivariate analysis demonstrated that higher bone marrow blast cell percentage at diagnosis, CR after more than one course of chemotherapy and less than six courses of consolidation chemotherapy were risk prognostic factors in childhood AML other than APL (P < 0.05). CONCLUSION: The prognosis of childhood APL is better, while of childhood t(8;21) AML is no better than other FAB subtypes. PMID- 17278431 TI - [Effect of diallyl disulfide on the expression and secretion of VEGF in HL-60 cells]. AB - OBJECTIVE: To investigate the proliferation inhibition of human leukemic cell line HL-60 and the expression of vascular endothelial growth factor (VEGF) mRNA and secretion of VEGF protein in HL-60 cells treated with diallyl disulfide (DADS). METHODS: MTT was used to test the cell growth, semi-quantitative RT-PCR and ELISA to study the expression of VEGF mRNA and secretion of VEGF protein. RESULTS: DADS significantly inhibited proliferation of HL-60 cell and the inhibiting effects showed a dose (r > 0.9, P < 0.01) and time-dependent( r > 0.7, P < 0.01) manner. The expression of VEGF mRNA and secretion of VEGF protein could be down regulated by 0.625, 1.250, and 2.500 microg/mL DADS in HL-60 cells for 24,48 and 72 hours exposure and the effects also showed dose -dependence(r > 0.9, P < 0.01). The growth inhibition rates of DADS in HL-60 cells at three dosages for 24 hours were (8.19 +/- 3.34)%, (16.79 +/- 2.07)% and (21.30 +/- 2.72)%, those for 48 hours were (11.93 +/- 3.93)%, (22.81 +/- 2.31)% and (30.74 +/- 2.03)%, for 72 hours were (16.68 +/- 2.37)%, (28.54 +/- 3.26)% and (36.59 +/- 2.37)% respectively, The difference between the DADS-treated and untreated HL-60 cells was statistically significant (P < 0.01). There were also statistically significant differences among the three groups of different dosages (P < 0.01). CONCLUSION: DADS can effectively inhibit the proliferation of HL-60 cells. DADS probably exerts its anti-leukemia effects by reducing the expression of VEGF mRNA and secretion of VEGF protein in HL-60 cells. PMID- 17278432 TI - [Analysis on tongue manifestations of 488 cases of Warm disease in Qing Dynasty]. AB - 488 cases of warm disease with tongue diagnosis picked up from 29 monographs providing materials of tongue diagnosis are sorted out of 51 monographs of medical records in the Qing Dynasty. Statistics and analysis were made on these 488 cases of tongue diagnoses, according to the classification of tongue manifestations in the Textbook of Diagnostics of Chinese Medicine for TCM schools of higher education. Results showed that, among all the cases, the recording rate of tongue fur was 65. 16% and was the highest one of the recording materials. The frequencies of different fur recorded from high to low were yellow, white and black. From 1850 to 1911 in the Qing Dynasty, occurrence rate of tongue coating had changed. Those of white, yellow and compound fur were increased. On the contrary, that of black fur was decreased. The recording rate of the color of tongue proper was 23. 16%, among which the proportions of red and crimson tongue were the highest. The recording rate of fur quality of fur was 37. 7%. From 1850 to 1911 in the Qing Dynasty, the recording rate of greasy fur reached the first place in fur quality. Tongue diagnosis was applied in warm- heat and damp-heat types of Warm Disease and pestilence. PMID- 17278429 TI - [Analysis of angiogenesis related proteins and its implication in type-2 hereditary hemorrhagic telangiectasia]. AB - OBJECTIVE: To detect the level of transforming growth factor-beta1 (TGF-beta1), TGF-beta2, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor-alpha (PDGFRalpha) in plasma and peripheral blood leukocytes in a hereditary hemorrhagic telangiectasia type 2 (HHT-2) family, and explore the implication of angiogenesis related proteins in HHT-2 pathogenesis. METHODS: The diagnosis of the HHT-2 patient was based on clinical features and further confirmed by determining a C1231T mutation of activin receptor-like kinase 1 (ALK1) gene. Five other new members in this family were evaluated with ALK1 gene screening and clinical manifestation. Plasma level of TGF-beta1, TGF-beta2 or VEGF was measured by ELISA, and the expression of PDGFRalpha,TGF-beta1, and VEGF in peripheral blood leukocytes by flow cytometry combined with direct or indirect immunofluorescence. RESULTS: No C1231T mutation was detected in exon 8 of ALK1 gene in the 5 new members. Plasma TGF-beta1 and TGF-beta2 concentration in 3 affected HHT case was (16 954 +/- 3 709) ng/L and (11 548 +/- 2 611) ng/L, respectively, compared with that of normal control, the difference was not significant (P > 0.05). VEGF concentration in the 3 HHT patients, 6 unaffected family members and 6 normal controls was (179.2 +/- 22.0) microg/L, (149.8 +/- 22.7) microg/L and (132.9 +/- 21.0) microg/ L, respectively. Plasma VEGF level in HHT patients was significantly higher than that in normal subjects (P < 0.025). Peripheral leukocyte PDGFRalpha and VEGF in HHT patients and unaffected family members were markedly higher than that of normal control (P < 0.05 and P < 0.02), while TGF-beta1 distribution was similar in HHT patients and normal subjects. CONCLUSION: Compared with normal controls there is no difference in plasma TGF beta1 concentration on peripheral leukocytes of HHT patients. Plasma VEGF concentration or leukocytes VEGF expression in HHT is significantly higher than that of normal subjects. Leukocytes PDGFRalpha expression in HHT is significantly higher than that of normal control. These changes may be associated with a compensable mechanism in HHT. PMID- 17278433 TI - [On authors of Lingnan Weisheng Fang (Lingnan Hygiene Prescription)]. AB - By applying philological methods, the authors of different chapters of Lingnan Weisheng Fang (Lingnan Hygiene Prescription) were investigated based on historical materials and epitaphs. The date of compilation of the book was also approximately investigated. PMID- 17278434 TI - [Zhang Zhongjings lost formulas not included in Shanghan Lun (Treatise on Cold Pathogenic Diseases)]. AB - In addition to the medical formulas of Zhang Zhongjing mostly existed in Shanghan Lun (Treatise on Cold Pathogenic Diseases) and Jinkui Yaolve Fanglun (Synopsis of Prescriptions of the Golden Chamber ) collated by Lin Yi in the Song Dynasty, there are some other lost formulas scattered in Beiji Qianjin Yao Fang (Essential Recipes for Emergent Use Worth a Thousand Gold), Qianjin Yi Fang (A Supplement to Recipes Worth a Thousand Gold ) , Waitai Miyao (Arcane Essentials from the Imperial Library) , written in the Tang Dynasty, and Taiping Shenghui Fang (Tiping Holy Prescriptions for Universal Relief) and Isimpo (Prescriptions from the Heart of Medicine)and those written in the Song Dynasty. Based on the textual research, collation, differentiation of Zhongjings formulas in different texts and medical works, the lost formulas of Zhongjing were collected besides those in Shanghan Lun (Treatise on Cold Pathogenic Diseases) and Jinkui Yaolve Fanglun (Synopsis of Prescriptions of the Golden Chamber), and then the state of the formulas were identified. PMID- 17278435 TI - [Exertion of dredging and guiding technique in Zhu Bing Yuan Hou Lun ( General Treatise on Causes and Manifestations of All Diseases)]. AB - Zhu Bing Yuan Hou Lun (General Treatise on Causes and Manifstations of All Diseases) is an immortal monograph of clinical pathology and science of clinical manifestations. It always encloses health preserving method and dredging and guiding technique for preventing and treating disease following the description of the various syndromes of a disease. Many contents about dredging and guiding technique recorded in the book were lost already, and the contents fully exert the technique. For instance, it explains the concrete method of interpreting the skill of doing the technique, elucidates the theories, explains the basic terms straightaway, and encloses the doctor's advises after doing the technique. The book emphasizes swallowing saliva when regulating qi, and preserving thoughts are combined when doing the technique, as well as diet indications and contraindications. The "six- word pithy knack" is determined firstly in the book and paired with different Zang-fu organs, as well as emphasizing the performance of the technique based on syndrome differentiation. PMID- 17278437 TI - [Investigation of editions of Wenrebing Zhinan Ji (Collection of Guide for Warm Heat Disease)]. AB - Wenrebing Zhinan Ji (Collection of Guide for Warm Heat Disease) was not a lengthy work, but it had quite a few influences among the medical works of warm heat disease. Regarding the evolvement of the edition and contents of the book, relative records in some authoritative bibliographic tool references had mistakes, errors and defects. The records of the author were complicated and confusing. There were five versions of the book recorded in the Quanguo Zhongyi Tushu Lianhe Mulu (Nationwide Union Catalog of Books of Traditional Chinese Medicine). The study found that there are other versions to be added here, including Wenre Zuiyan (Verbosity of Warm Heat Disease) supplemented to Sanjia Yian Heke (United Collection of Medical Cases of Three Physicians) and Wenre Jingwei (Longitude and Latitude of Warm Heat Diseases) by Wang Mengying, with the xylographic version of Guangxu of the Qing Dynasty excluded. Each version possesses its own special features and values. PMID- 17278436 TI - [Study on Jisi Yi'an (Medical Cases of Multitude Thought) of Yi Jusun, a famous doctor of Lingnan region]. AB - Textual research was made on Jisi Yian (Medical Cases of Multitude Thought), a book of medical cases written by Yi Jusun, whose nickname is Chubai, one of the "Four Warriors of Buddha", modern four heads school in favor of classical prescriptions in Lingnan region. The now extant hand- written copy of this medical book is collected in the Shu Renzhi's Juxiang Hall in the early period of Republic of China. Analyses are made on the medical records of treating difficult and critical illness applied by Yi Jusun. The Shengma Biejia San (skunk bugbane and Carapax Amydae Powder) proposed by him played a vital role in preventing and curing plague in modern Guangdong Province. PMID- 17278438 TI - [Studies on developmental features of theories of syndrome differentiation of zang-fu viscera in Qin and Han Dynasties]. AB - The formation of the theories of visceral manifestations as well as channels and collaterals in the books Huangdi Neijing (Inner Canon of Huangdi) and Nan Jing (Classic of Questioning) laid down the theoretical foundation for the theories of syndrome differentiation of zang--fu viscera. From the early occurrence of syndrome classification to that of the disease manifestations of zang and fu viscera, the theories of syndrome differentiation of zang--fu viscera were basically not put into practice until Shanghan Zabing Lun (Treatise on Cold Pathogenic and Miscellaneous Diseases) appeared. The theories of syndrome differentiation of zang--fu viscera in the Qin and Han Dynasties were not systematic and were scattered, indicating that it was a period of gestation for the theories. PMID- 17278439 TI - [Research and headstream of scope of chest bi]. AB - The name of chest bi was originated from Neijing (Internal Canon), with its discussion related to the lung. The concept of chest bi was broadened and varied in the latter works of traditional Chinese Medicine in later generations. Nowadays, the textbook of Internal Medicine of Chinese Medicine, the state and the professional standards define thechest bi to coronary heart disease, thus reducing the scope of chest bi. PMID- 17278440 TI - [Investigation of acupoints on Du (governor) channel]. AB - The origin and variation of acupoints on the Du channel are investigated by analyzing and studying the number and distribution of points recorded in the ancient medical works. It is found that the amount and distribution of the points were different in different ages. The distributions of the points were not only located on the midline of the face, head, nape and posterior midline but also on both sides of the spine from the period of Neijing (Inner Canon) to that of Zhenjiu Jiayi Jing (A-B Classic of Acupuncture and Moxibustion). Since the period of Tongren Shuxue Zhenjiu Tujing (Illustration Classic of Acupoints on Bronze Statue) in the Song dynasty, only those points of the midline from the face, nape to the spine are remained there until now. Meanwhile, the amount of points were also varied because of the cognition to the points on the spine. Huangdi Neijing Taisu (Grand Simplicity of Inner Canon of Huangdi) compiled in the Tang Dynasty first mentioned the arguments about the varied points on the channel. The records by Yang Shangshan and Wang Bing indicate that the main differences on the cognition of the channel andits points appeared during the period of the Tang Dynasty to the Song Dynasty. PMID- 17278441 TI - [The origin and development of temporomandibular dislocation reduced intraorally ]. AB - The earliest records of temporomandibular dislocation reduced inside the oral cavity can be found in Yinshu (The Pulling Book) unearthed in Han Bamboo script in 1984 in Zhangjiashan, Hubei Province. Later on, physicians of different dynasties developed the etiology, pathogenesis, symptoms, signs and treatment of temporomandibular dislocation on the basis of Yinshu (The Pulling Book). Although the manipulations recorded in Yinshu (The Pulling Book) were rather simple, but they were used continuously as a basic clinical manipulation of orthopaedics. PMID- 17278442 TI - [Huang Kuan,the first doctor wno studied abroad in the United States and the United Kingdom]. AB - Huang Kuan was the first doctor western medicine of who studied basic sciences at Monson Academy in US in 1 847. Two years later, he went over to Scotland, wheve, he had complete medical training and received his medical degree at Edinburgh University in UK. He made great contribution to spread western medicine from West to China. At that time he was known as one of the best surgeons in the east of the Cape of Good Hope. His achievement is unforgettable in medical history of China. PMID- 17278444 TI - [Probing the cause on Wang Qingrens idea of "Fallacious theory, effective prescription" of Wang Qingren]. AB - The theory of human body in Yilin Gaicuo (Correction on Errors in Medical Classics) by Wang Qingren in late Qing Dynasty is different from that of traditional Chinese Medicine and that of anatomy of western medicine. However, the prescriptions recorded in Yilin Gaicuo (Correction on Errors in Medical Classics) are indeed effective clinically. The paradox of "Fallacious theory, effective prescription" suggests that the theories of Wang Qingren are not superficial in anatomy. By carefully analyzing the concept of zang-fu organs and concept of qi and blood as well as the theory of human body in Yilin Gaicuo (Correction on Errors in Medical Classics), although many viewpoints of theories of Wang Qingren deviates from that of traditional Chinese Medicine, they inherits the qi and blood concept, the core theory of Chinese Medicine. Therefore, the theories belong to the theoretical scope of Chinese Medicine. The root of "Fallacious theory, effective prescription" is in the heritage of the qi and blood concept. The set view of Wang Qingren in criticizing the theories of traditional Chinese Medicine and establishing new theories revealed in this process possesses the significance of revelation to the contemporary Chinese Medicine. PMID- 17278443 TI - [Fifty years of medical education of Hainan Province]. AB - The 50 years' history of medical education of Hainan Province in new China was investigated in the study. The developmental histories of Hainan College of Medicine and Hainan Secondary Health School were stated, dealing with the enhancement of the cultivation of health professionals to provide public health service and the great improvement of the condition of lacking doctor and medicine in hinterland area of the province. PMID- 17278445 TI - Insurer's decision, your responsibility. PMID- 17278446 TI - Making change work. PMID- 17278447 TI - Trashed on the Web: now what? PMID- 17278448 TI - Time to add a second shift? PMID- 17278449 TI - NPs and PAs: a seller's market. PMID- 17278450 TI - One good move made all the difference. PMID- 17278452 TI - Circulus arteriosus cerebri: a study of variation in the fetal and adult human brains of south Indians. AB - The Circle of Willis or Circulus Arteriosus Cerebri and its branches are subject to many variations. The Circle of Willis with a classical description is very rare. The constituent arteries forming the circle vary greatly in size in different individuals and on two sides in the same subject. Study by dissection or by angiographic methods by several workers has shown that deviations from the normal pattern occur in a very high proportion of cases. There are differing views regarding the variations in the circle. Thus, this study was done to compare our findings with the others. In the present study, each artery taking part in the circle has been described in relation to the length, size and its origin separately and the findings have been compared. PMID- 17278451 TI - [Site specific mutagenesis by homologous recombination in embryonic stem cells]. AB - Twenty years ago, the production of mice whose genomes have been deliberatly modified revolutionised biology. Indeed, it is now possible to eliminate a gene's expression to various levels in desired locations, and also to broadcast these genetic modifications created in vitro to the progeny. The isolation and culture of embryonic stem cells (ES) and the discovery of the mechanism of homologous recombination between two sequences of DNA in the 80's, have contributed to the development of site-directed mutagenesis. Today, site specific mutagenesis by homologous recombination in embryonic stem cells is a powerful technique and is widely used throughout the world. In parallel, new techniques to invalidate targeted genes are emerging. These genetics tools, which we will introduce, allow for a better understanding of a gene's function both in fundamental and clinical research. It is now possible to create murine models of human genetic diseases including Lesch-Nhyan syndrome, Adenomatous Polyposis and Duchenne muscular dystrophy which we will discuss as examples. PMID- 17278453 TI - [Increase neuroanatomic definition of nervous central system structures by addition on slices of ferric chloride]. AB - The authors have described a new method of coloration on anatomic slices of the central nervous system realised on formolated subjects. They have presented their first results on their experiences carried out on the different levels of the brain, and this simple method of proceeding shows how interesting it could be for all practicians of Neurosciences and for the teaching of Neuroanatomy. PMID- 17278454 TI - Assessment of the main pancreatic duct using computed tomography with multiplanar reconstructions. AB - The aim of this study was to assess the morphology of the main pancreatic duct (MPD) using multiplanar reconstructions and to compare this with the morphology of the MPD of anatomic subjects. MATERIALS AND METHODS: The morphology of the MPD was studied by means of multiplanar reconstructions obtained on the one hand from thin tomodensitometric slices and on the other hand from the dissection of anatomic subjects. This study involved 15 subjects in each group. RESULTS: Full multiplanar reconstruction was obtained in 13 cases. In 2 cases, the isthmus did not appear in the reconstructions. The morphology of the MPD was similar in both groups. The length of the MPD was identical at the head and isthmus of the pancreas in both groups but was greater in the dissection group than in the reconstruction group in the body and tail areas of the pancreas. The diameter of the MPD was greater at the head of the pancreas in the dissection group and was identical in both groups for the other segments of the MPD. CONCLUSIONS: Multiplanar tomodensitometric reconstruction of the main pancreatic duct is feasible. This new technique, currently under evaluation, could allow the study of canalar pathologies of the pancreas through tomodensitometry. PMID- 17278455 TI - Co-existence of the pectoralis quartus and pectoralis intermedius muscles. AB - During the routine dissection studies on the right side of a 56-year-old female cadaver we encountered co-existence of the pectoralis quartus and pectoralis intermedius muscles. The pectoralis quartus originated from the costochondral junction of the fifth and sixth ribs, and then extended laterally under the border of pectoralis major muscle, but it was entirely separate from it. The pectoralis quartus formed a long flat band with an average width of 1.5 cm. It then inserted as an aponeurosis to the both of lateral lip of the intertubercular groove of the humerus and tendon of the short head of the biceps brachii muscle. Furthermore, the pectoralis intermedius muscle was a fleshy slip between the pectoralis minor and pectoralis quartus muscles and arose from the third and fourth ribs. It then united to the tendon of the short head of the biceps brachii muscle two cm below the coracoid process. PMID- 17278456 TI - Bifid liver presenting with anomalous quadrate and caudate lobes and a transverse gallbladder. AB - The current Observation reports multiple anomalies of the liver of a 55-year-old male cadaver. Observations revealed the presence of anomalies on the diaphragmatic and visceral surfaces of the liver. The diaphragmatic surface presented with a deep furrow that run obliquely from the fissure for the inferior vena cava to the inferior border of the liver. It divided the liver partially into the right and left segments that remained united by the liver tissue that measured about 0.7 cm thick. The two segments were easily pulled apart for up to 3 cm. A similar fissure did not appear on the visceral surface. The visceral surface presented with multiple anomalies that included a vertically oriented porta hepatis, abnormal Y-shaped fissures on the right lobe, transverse gallbladder, absence of the caudate process on the caudate lobe, abnormal quadrate lobe, and transverse fissure on the right lobe. The three fissures that formed a Y-shaped configuration delineated the quadrate lobe. The right and left arms of the Y-shaped fissure terminated in the porta hepatis. Congenital anomalies of the adult liver are rare; therefore continued documentation of such anomalies remains to be important in medical sciences and in the understanding of liver ontogeny. PMID- 17278457 TI - Reduced support vector machines: a statistical theory. AB - In dealing with large data sets, the reduced support vector machine (RSVM) was proposed for the practical objective to overcome some computational difficulties as well as to reduce the model complexity. In this paper, we study the RSVM from the viewpoint of sampling design, its robustness, and the spectral analysis of the reduced kernel. We consider the nonlinear separating surface as a mixture of kernels. Instead of a full model, the RSVM uses a reduced mixture with kernels sampled from certain candidate set. Our main results center on two major themes. One is the robustness of the random subset mixture model. The other is the spectral analysis of the reduced kernel. The robustness is judged by a few criteria as follows: 1) model variation measure; 2) model bias (deviation) between the reduced model and the full model; and 3) test power in distinguishing the reduced model from the full one. For the spectral analysis, we compare the eigenstructures of the full kernel matrix and the approximation kernel matrix. The approximation kernels are generated by uniform random subsets. The small discrepancies between them indicate that the approximation kernels can retain most of the relevant information for learning tasks in the full kernel. We focus on some statistical theory of the reduced set method mainly in the context of the RSVM. The use of a uniform random subset is not limited to the RSVM. This approach can act as a supplemental algorithm on top of a basic optimization algorithm, wherein the actual optimization takes place on the subset-approximated data. The statistical properties discussed in this paper are still valid. PMID- 17278458 TI - Backpropagation algorithms for a broad class of dynamic networks. AB - This paper introduces a general framework for describing dynamic neural networks- the layered digital dynamic network (LDDN). This framework allows the development of two general algorithms for computing the gradients and Jacobians for these dynamic networks: backpropagation-through-time (BPTT) and real-time recurrent learning (RTRL). The structure of the LDDN framework enables an efficient implementation of both algorithms for arbitrary dynamic networks. This paper demonstrates that the BPTT algorithm is more efficient for gradient calculations, but the RTRL algorithm is more efficient for Jacobian calculations. PMID- 17278459 TI - A kernel-based two-class classifier for imbalanced data sets. AB - Many kernel classifier construction algorithms adopt classification accuracy as performance metrics in model evaluation. Moreover, equal weighting is often applied to each data sample in parameter estimation. These modeling practices often become problematic if the data sets are imbalanced. We present a kernel classifier construction algorithm using orthogonal forward selection (OFS) in order to optimize the model generalization for imbalanced two-class data sets. This kernel classifier identification algorithm is based on a new regularized orthogonal weighted least squares (ROWLS) estimator and the model selection criterion of maximal leave-one-out area under curve (LOO-AUC) of the receiver operating characteristics (ROCs). It is shown that, owing to the orthogonalization procedure, the LOO-AUC can be calculated via an analytic formula based on the new regularized orthogonal weighted least squares parameter estimator, without actually splitting the estimation data set. The proposed algorithm can achieve minimal computational expense via a set of forward recursive updating formula in searching model terms with maximal incremental LOO AUC value. Numerical examples are used to demonstrate the efficacy of the algorithm. PMID- 17278460 TI - A fuzzy min-max neural network classifier with compensatory neuron architecture. AB - This paper proposes a fuzzy min-max neural network classifier with compensatory neurons (FMCNs). FMCN uses hyperbox fuzzy sets to represent the pattern classes. It is a supervised classification technique with new compensatory neuron architecture. The concept of compensatory neuron is inspired from the reflex system of human brain which takes over the control in hazardous conditions. Compensatory neurons (CNs) imitate this behavior by getting activated whenever a test sample falls in the overlapped regions amongst different classes. These neurons are capable to handle the hyperbox overlap and containment more efficiently. Simpson used contraction process based on the principle of minimal disturbance, to solve the problem of hyperbox overlaps. FMCN eliminates use of this process since it is found to be erroneous. FMCN is capable to learn the data online in a single pass through with reduced classification and gradation errors. One of the good features of FMCN is that its performance is less dependent on the initialization of expansion coefficient, i.e., maximum hyperbox size. The paper demonstrates the performance of FMCN by comparing it with fuzzy min-max neural network (FMNN) classifier and general fuzzy min-max neural network (GFMN) classifier, using several examples. PMID- 17278461 TI - Dynamics of winner-take-all competition in recurrent neural networks with lateral inhibition. AB - This paper studies the behavior of recurrent neural networks with lateral inhibition. Such network architecture is important in biological neural systems. General conditions determining the existence, number, and stability of network equilibria are derived. The manner in which these features depend upon steepness of neuronal activation functions and the strength of lateral inhibition is demonstrated for a broad range of nondecreasing activation functions including the discontinuous threshold function which represents the infinite gain limit. For uniform lateral inhibitory networks, the lateral inhibition is shown to sharpen neuron output patterns by increasing separation of suprathreshold activity levels of competing neurons. This results in the tendency of one neuron's output to dominate those of the others which can afford a "winner-take all" (WTA) mechanism. Importantly, multiple stable equilibria may exist and shifts in inputs levels may yield network state transitions that exhibit hysteresis. A limitation of using lateral inhibition to implement WTA is further demonstrated. The possible significance of these identified network dynamics to physiology and pathophysiology of the striatum (particularly in Parkinsonian rest tremor) is discussed. PMID- 17278463 TI - Design of asymptotic estimators: an approach based on neural networks and nonlinear programming. AB - A methodology to design state estimators for a class of nonlinear continuous-time dynamic systems that is based on neural networks and nonlinear programming is proposed. The estimator has the structure of a Luenberger observer with a linear gain and a parameterized (in general, nonlinear) function, whose argument is an innovation term representing the difference between the current measurement and its prediction. The problem of the estimator design consists in finding the values of the gain and of the parameters that guarantee the asymptotic stability of the estimation error. Toward this end, if a neural network is used to take on this function, the parameters (i.e., the neural weights) are chosen, together with the gain, by constraining the derivative of a quadratic Lyapunov function for the estimation error to be negative definite on a given compact set. It is proved that it is sufficient to impose the negative definiteness of such a derivative only on a suitably dense grid of sampling points. The gain is determined by solving a Lyapunov equation. The neural weights are searched for via nonlinear programming by minimizing a cost penalizing grid-point constraints that are not satisfied. Techniques based on low-discrepancy sequences are applied to deal with a small number of sampling points, and, hence, to reduce the computational burden required to optimize the parameters. Numerical results are reported and comparisons with those obtained by the extended Kalman filter are made. PMID- 17278462 TI - Basic difference between brain and computer: integration of asynchronous processes implemented as hardware model of the retina. AB - There exists a common view that the brain acts like a Turing machine: The machine reads information from an infinite tape (sensory data) and, on the basis of the machine's state and information from the tape, an action (decision) is made. The main problem with this model lies in how to synchronize a large number of tapes in an adaptive way so that the machine is able to accomplish tasks such as object classification. We propose that such mechanisms exist already in the eye. A popular view is that the retina, typically associated with high gain and adaptation for light processing, is actually performing local preprocessing by means of its center-surround receptive field. We would like to show another property of the retina: The ability to integrate many independent processes. We believe that this integration is implemented by synchronization of neuronal oscillations. In this paper, we present a model of the retina consisting of a series of coupled oscillators which can synchronize on several scales. Synchronization is an analog process which is converted into a digital spike train in the output of the retina. We have developed a hardware implementation of this model, which enables us to carry out rapid simulation of multineuron oscillatory dynamics. We show that the properties of the spike trains in our model are similar to those found in vivo in the cat retina. PMID- 17278464 TI - The AIC criterion and symmetrizing the Kullback-Leibler divergence. AB - The Akaike information criterion (AIC) is a widely used tool for model selection. AIC is derived as an asymptotically unbiased estimator of a function used for ranking candidate models which is a variant of the Kullback-Leibler divergence between the true model and the approximating candidate model. Despite the Kullback-Leibler's computational and theoretical advantages, what can become inconvenient in model selection applications is their lack of symmetry. Simple examples can show that reversing the role of the arguments in the Kullback Leibler divergence can yield substantially different results. In this paper, three new functions for ranking candidate models are proposed. These functions are constructed by symmetrizing the Kullback-Leibler divergence between the true model and the approximating candidate model. The operations used for symmetrizing are the average, geometric, and harmonic means. It is found that the original AIC criterion is an asymptotically unbiased estimator of these three different functions. Using one of these proposed ranking functions, an example of new bias correction to AIC is derived for univariate linear regression models. A simulation study based on polynomial regression is provided to compare the different proposed ranking functions with AIC and the new derived correction with AICc. PMID- 17278465 TI - Distribution modeling of nonlinear inverse controllers under a Bayesian framework. AB - The inverse controller is traditionally assumed to be a deterministic function. This paper presents a pedagogical methodology for estimating the stochastic model of the inverse controller. The proposed method is based on Bayes' theorem. Using Bayes' rule to obtain the stochastic model of the inverse controller allows the use of knowledge of uncertainty from both the inverse and the forward model in estimating the optimal control signal. The paper presents the methodology for general nonlinear systems and is demonstrated on nonlinear single-input-single output (SISO) and multiple-input-multiple-output (MIMO) examples. PMID- 17278466 TI - Nonlinear adaptive wavelet control using constructive wavelet networks. AB - In this paper, an adaptive wavelet-network-based control approach is proposed for highly nonlinear uncertain dynamical systems. Wavelet network, as a kind of universal approximator, has two novel properties--orthonormality and multiresolution. The orthonormal property ensures that adding a new resolution (new wavelets) does not affect the existing wavelet network that may have been well tuned. In the sequel, the online adjustment of the structure of the nonlinear adaptive wavelet controller (AWC) can be done in a constructive manner by gradually increasing the network resolution. The multiresolution property, on the other hand, assures a guaranteed improvement of the approximation precision when a new resolution is added. In real life problems we are unable to know the adequate size of a network, either a neural network (NN) or a wavelet network, to produce the required approximation precision. By virtue of the novel wavelet network properties, a coarse or very simple structure can be selected first. If the system fails to converge after the elapse of a dwell time, a new wavelet resolution is considered to be necessary and added directly. In this manner, the AWC can be easily constructed and tuned from the coarse to finer levels until the performance requirement is satisfied. The trial and error way of selecting the network structure, which may lead to either an inadequate or a highly redundant structure, can be avoided. In this paper, the proposed adaptive wavelet network is applied first to a class of nonlinear dynamical systems with a partially known model and an affine-in-input structure. Then, the adaptive wavelet network is applied to a class of nonlinear nonaffine dynamical systems. PMID- 17278468 TI - A kernel approach for semisupervised metric learning. AB - While distance function learning for supervised learning tasks has a long history, extending it to learning tasks with weaker supervisory information has only been studied recently. In particular, some methods have been proposed for semisupervised metric learning based on pairwise similarity or dissimilarity information. In this paper, we propose a kernel approach for semisupervised metric learning and present in detail two special cases of this kernel approach. The metric learning problem is thus formulated as an optimization problem for kernel learning. An attractive property of the optimization problem is that it is convex and, hence, has no local optima. While a closed-form solution exists for the first special case, the second case is solved using an iterative majorization procedure to estimate the optimal solution asymptotically. Experimental results based on both synthetic and real-world data show that this new kernel approach is promising for nonlinear metric learning. PMID- 17278467 TI - Uncertainty estimation using fuzzy measures for multiclass classification. AB - Uncertainty arises in classification problems when the input pattern is not perfect or measurement error is unavoidable. In many applications, it would be beneficial to obtain an estimate of the uncertainty associated with a new observation and its membership within a particular class. Although statistical classification techniques base decision boundaries according to the probability distributions of the patterns belonging to each class, they are poor at supplying uncertainty information for new observations. Previous research has documented a multiarchitecture, monotonic function neural network model for the representation of uncertainty associated with a new observation for two-class classification. This paper proposes a modification to the monotonic function model to estimate the uncertainty associated with a new observation for multiclass classification. The model, therefore, overcomes a limitation of traditional classifiers that base decisions on sharp classification boundaries. As such, it is believed that this method will have advantages for applications such as biometric recognition in which the estimation of classification uncertainty is an important issue. This approach is based on the transformation of the input pattern vector relative to each classification class. Separate, monotonic, single-output neural networks are then used to represent the "degree-of-similarity" between each input pattern vector and each class. An algorithm for the implementation of this approach is proposed and tested with publicly available face-recognition data sets. The results indicate that the suggested approach provides similar classification performance to conventional principle component analysis (PCA) and linear discriminant analysis (LDA) techniques for multiclass pattern recognition problems as well as providing uncertainty information caused by misclassification. PMID- 17278469 TI - A method of face recognition based on fuzzy c-means clustering and associated sub NNs. AB - The face is a complex multidimensional visual model and developing a computational model for face recognition is difficult. In this paper, we present a method for face recognition based on parallel neural networks. Neural networks (NNs) have been widely used in various fields. However, the computing efficiency decreases rapidly if the scale of the NN increases. In this paper, a new method of face recognition based on fuzzy clustering and parallel NNs is proposed. The face patterns are divided into several small-scale neural networks based on fuzzy clustering and they are combined to obtain the recognition result. In particular, the proposed method achieved a 98.75 % recognition accuracy for 240 patterns of 20 registrants and a 99.58% rejection rate for 240 patterns of 20 nonregistrants. Experimental results show that the performance of our new face-recognition method is better than those of the backpropagation NN (BPNN) system, the hard c-means (HCM) and parallel NNs system, and the pattern-matching system. PMID- 17278470 TI - Reducing and filtering point clouds with enhanced vector quantization. AB - Modern scanners are able to deliver huge quantities of three-dimensional (3-D) data points sampled on an object's surface, in a short time. These data have to be filtered and their cardinality reduced to come up with a mesh manageable at interactive rates. We introduce here a novel procedure to accomplish these two tasks, which is based on an optimized version of soft vector quantization (VQ). The resulting technique has been termed enhanced vector quantization (EVQ) since it introduces several improvements with respect to the classical soft VQ approaches. These are based on computationally expensive iterative optimization; local computation is introduced here, by means of an adequate partitioning of the data space called hyperbox (HB), to reduce the computational time so as to be linear in the number of data points N, saving more than 80% of time in real applications. Moreover, the algorithm can be fully parallelized, thus leading to an implementation that is sublinear in N. The voxel side and the other parameters are automatically determined from data distribution on the basis of the Zador's criterion. This makes the algorithm completely automatic. Because the only parameter to be specified is the compression rate, the procedure is suitable even for nontrained users. Results obtained in reconstructing faces of both humans and puppets as well as artifacts from point clouds publicly available on the web are reported and discussed, in comparison with other methods available in the literature. EVQ has been conceived as a general procedure, suited for VQ applications with large data sets whose data space has relatively low dimensionality. PMID- 17278472 TI - Model risk for European-style stock index options. AB - In empirical modeling, there have been two strands for pricing in the options literature, namely the parametric and nonparametric models. Often, the support for the nonparametric methods is based on a benchmark such as the Black-Scholes (BS) model with constant volatility. In this paper, we study the stochastic volatility (SV) and stochastic volatility random jump (SVJ) models as parametric benchmarks against feedforward neural network (FNN) models, a class of neural network models. Our choice for FNN models is due to their well-studied universal approximation properties of an unknown function and its partial derivatives. Since the partial derivatives of an option pricing formula are risk pricing tools, an accurate estimation of the unknown option pricing function is essential for pricing and hedging. Our findings indicate that FNN models offer themselves as robust option pricing tools, over their sophisticated parametric counterparts in predictive settings. There are two routes to explain the superiority of FNN models over the parametric models in forecast settings. These are nonnormality of return distributions and adaptive learning. PMID- 17278471 TI - Face recognition using total margin-based adaptive fuzzy support vector machines. AB - This paper presents a new classifier called total margin-based adaptive fuzzy support vector machines (TAF-SVM) that deals with several problems that may occur in support vector machines (SVMs) when applied to the face recognition. The proposed TAF-SVM not only solves the overfitting problem resulted from the outlier with the approach of fuzzification of the penalty, but also corrects the skew of the optimal separating hyperplane due to the very imbalanced data sets by using different cost algorithm. In addition, by introducing the total margin algorithm to replace the conventional soft margin algorithm, a lower generalization error bound can be obtained. Those three functions are embodied into the traditional SVM so that the TAF-SVM is proposed and reformulated in both linear and nonlinear cases. By using two databases, the Chung Yuan Christian University (CYCU) multiview and the facial recognition technology (FERET) face databases, and using the kernel Fisher's discriminant analysis (KFDA) algorithm to extract discriminating face features, experimental results show that the proposed TAF-SVM is superior to SVM in terms of the face-recognition accuracy. The results also indicate that the proposed TAF-SVM can achieve smaller error variances than SVM over a number of tests such that better recognition stability can be obtained. PMID- 17278473 TI - Direction-dependent learning approach for radial basis function networks. AB - Direction-dependent scaling, shaping, and rotation of Gaussian basis functions are introduced for maximal trend sensing with minimal parameter representations for input output approximation. It is shown that shaping and rotation of the radial basis functions helps in reducing the total number of function units required to approximate any given input-output data, while improving accuracy. Several alternate formulations that enforce minimal parameterization of the most general radial basis functions are presented. A novel "directed graph" based algorithm is introduced to facilitate intelligent direction based learning and adaptation of the parameters appearing in the radial basis function network. Further, a parameter estimation algorithm is incorporated to establish starting estimates for the model parameters using multiple windows of the input-output data. The efficacy of direction-dependent shaping and rotation in function approximation is evaluated by modifying the minimal resource allocating network and considering different test examples. The examples are drawn from recent literature to benchmark the new algorithm versus existing methods. PMID- 17278474 TI - Bayesian neural networks for internet traffic classification. AB - Internet traffic identification is an important tool for network management. It allows operators to better predict future traffic matrices and demands, security personnel to detect anomalous behavior, and researchers to develop more realistic traffic models. We present here a traffic classifier that can achieve a high accuracy across a range of application types without any source or destination host-address or port information. We use supervised machine learning based on a Bayesian trained neural network. Though our technique uses training data with categories derived from packet content, training and testing were done using features derived from packet streams consisting of one or more packet headers. By providing classification without access to the contents of packets, our technique offers wider application than methods that require full packet/payloads for classification. This is a powerful advantage, using samples of classified traffic to permit the categorization of traffic based only upon commonly available information. PMID- 17278475 TI - The impact of arithmetic representation on implementing MLP-BP on FPGAs: a study. AB - In this paper, arithmetic representations for implementing multilayer perceptrons trained using the error backpropagation algorithm (MLP-BP) neural networks on field-programmable gate arrays (FPGAs) are examined in detail. Both floating point (FLP) and fixed-point (FXP) formats are studied and the effect of precision of representation and FPGA area requirements are considered. A generic very high speed integrated circuit hardware description language (VHDL) program was developed to help experiment with a large number of formats and designs. The results show that an MLP-BP network uses less clock cycles and consumes less real estate when compiled in an FXP format, compared with a larger and slower functioning compilation in an FLP format with similar data representation width, in bits, or a similar precision and range. PMID- 17278476 TI - Dynamically reconfigurable silicon array of spiking neurons with conductance based synapses. AB - A mixed-signal very large scale integration (VLSI) chip for large scale emulation of spiking neural networks is presented. The chip contains 2400 silicon neurons with fully programmable and reconfigurable synaptic connectivity. Each neuron implements a discrete-time model of a single-compartment cell. The model allows for analog membrane dynamics and an arbitrary number of synaptic connections, each with tunable conductance and reversal potential. The array of silicon neurons functions as an address-event (AE) transceiver, with incoming and outgoing spikes communicated over an asynchronous event-driven digital bus. Address encoding and conflict resolution of spiking events are implemented via a randomized arbitration scheme that ensures balanced servicing of event requests across the array. Routing of events is implemented externally using dynamically programmable random-access memory that stores a postsynaptic address, the conductance, and the reversal potential of each synaptic connection. Here, we describe the silicon neuron circuits, present experimental data characterizing the 3 mm x 3 mm chip fabricated in 0.5-microm complementary metal-oxide semiconductor (CMOS) technology, and demonstrate its utility by configuring the hardware to emulate a model of attractor dynamics and waves of neural activity during sleep in rat hippocampus. PMID- 17278477 TI - An experimental study on nonlinear function computation for neural/fuzzy hardware design. AB - An experimental study on the influence of the computation of basic nodal nonlinear functions on the performance of (NFSs) is described in this paper. Systems' architecture size, their approximation capability, and the smoothness of provided mappings are used as performance indexes for this comparative paper. Two widely used kernel functions, the sigmoid-logistic function and the Gaussian function, are analyzed by their computation through an accuracy-controllable approximation algorithm designed for hardware implementation. Two artificial neural network (ANN) paradigms are selected for the analysis: backpropagation neural networks (BPNNs) with one hidden layer and radial basis function (RBF) networks. Extensive simulation of simple benchmark approximation problems is used in order to achieve generalizable conclusions. For the performance analysis of fuzzy systems, a functional equivalence theorem is used to extend obtained results to fuzzy inference systems (FISs). Finally, the adaptive neurofuzzy inference system (ANFIS) paradigm is used to observe the behavior of neurofuzzy systems with learning capabilities. PMID- 17278478 TI - Density-induced support vector data description. AB - The purpose of data description is to give a compact description of the target data that represents most of its characteristics. In a support vector data description (SVDD), the compact description of target data is given in a hyperspherical model, which is determined by a small portion of data called support vectors. Despite the usefulness of the conventional SVDD, however, it may not identify the optimal solution of target description especially when the support vectors do not have the overall characteristics of the target data. To address the issue in SVDD methodology, we propose a new SVDD by introducing new distance measurements based on the notion of a relative density degree for each data point in order to reflect the distribution of a given data set. Moreover, for a real application, we extend the proposed method for the protein localization prediction problem which is a multiclass and multilabel problem. Experiments with various real data sets show promising results. PMID- 17278479 TI - Rival-model penalized self-organizing map. AB - As a typical data visualization technique, self-organizing map (SOM) has been extensively applied to data clustering, image analysis, dimension reduction, and so forth. In a conventional adaptive SOM, it needs to choose an appropriate learning rate whose value is monotonically reduced over time to ensure the convergence of the map, meanwhile being kept large enough so that the map is able to gradually learn the data topology. Otherwise, the SOM's performance may seriously deteriorate. In general, it is nontrivial to choose an appropriate monotonically decreasing function for such a learning rate. In this letter, we therefore propose a novel rival-model penalized self-organizing map (RPSOM) learning algorithm that, for each input, adaptively chooses several rivals of the best-matching unit (BMU) and penalizes their associated models, i.e., those parametric real vectors with the same dimension as the input vectors, a little far away from the input. Compared to the existing methods, this RPSOM utilizes a constant learning rate to circumvent the awkward selection of a monotonically decreased function for the learning rate, but still reaches a robust result. The numerical experiments have shown the efficacy of our algorithm. PMID- 17278481 TI - Nonlinear knowledge in kernel approximation. AB - Prior knowledge over arbitrary general sets is incorporated into nonlinear kernel approximation problems in the form of linear constraints in a linear program. The key tool in this incorporation is a theorem of the alternative for convex functions that converts nonlinear prior knowledge implications into linear inequalities without the need to kernelize these implications. Effectiveness of the proposed formulation is demonstrated on two synthetic examples and an important lymph node metastasis prediction problem. All these problems exhibit marked improvements upon the introduction of prior knowledge over nonlinear kernel approximation approaches that do not utilize such knowledge. PMID- 17278480 TI - On the almost periodic solution of cellular neural networks with distributed delays. AB - By exponential dichotomy about differential equations, a formal almost periodic solution (APS) of a class of cellular neural networks (CNNs) with distributed delays is obtained. Then, within different normed spaces, several sufficient conditions guaranteeing the existence and uniqueness of an APS are proposed using two fixed-point theorems. Based on the continuity property and some inequality techniques, two theorems insuring the global stability of the unique APS are given. Comparing with known literatures, all conclusions are drawn with slacker restrictions, e.g., do not require the integral of the kernel function determining the distributed delays from zero to positive infinity to be one, and the activation functions to be bounded, etc.; besides, all criteria are obtained by different ways. Finally, two illustrative examples show the validity and that all criteria are easy to check and apply. PMID- 17278482 TI - Sparse model identification using a forward orthogonal regression algorithm aided by mutual information. AB - A sparse representation, with satisfactory approximation accuracy, is usually desirable in any nonlinear system identification and signal processing problem. A new forward orthogonal regression algorithm, with mutual information interference, is proposed for sparse model selection and parameter estimation. The new algorithm can be used to construct parsimonious linear-in-the-parameters models. PMID- 17278483 TI - New delay-dependent stability criteria for neural networks with time-varying delay. AB - In this letter, a new method is proposed for stability analysis of neural networks (NNs) with a time-varying delay. Some less conservative delay-dependent stability criteria are established by considering the additional useful terms, which were ignored in previous methods, when estimating the upper bound of the derivative of Lyapunov functionals and introducing the new free-weighting matrices. Numerical examples are given to demonstrate the effectiveness and the benefits of the proposed method. PMID- 17278484 TI - Thermoradiotherapy is underutilized for the treatment of cancer. PMID- 17278485 TI - Evaluating the impact of X-ray spectral shape on image quality in flat-panel CT breast imaging. AB - In recent years, there has been an increasing interest in exploring the feasibility of dedicated computed tomography (CT) breast imaging using a flat panel digital detector in a truncated cone-beam imaging geometry. Preliminary results are promising and it appears as if three-dimensional tomographic imaging of the breast has great potential for reducing the masking effect of superimposed parenchymal structure typically observed with conventional mammography. In this study, a mathematical framework used for determining optimal design and acquisition parameters for such a CT breast imaging system is described. The ideal observer signal-to-noise ratio (SNR) is used as a figure of merit, under the assumptions that the imaging system is linear and shift invariant. Computation of the ideal observer SNR used a parallel-cascade model to predict signal and noise propagation through the detector, as well as a realistic model of the lesion detection task in breast imaging. For all evaluations, the total mean glandular dose for a CT breast imaging study was constrained to be approximately equivalent to that of a two-view conventional mammography study. The framework presented was used to explore the effect of x-ray spectral shape across an extensive range of kVp settings, filter material types, and filter thicknesses. The results give an indication of how spectral shape can affect image quality in flat-panel CT breast imaging. PMID- 17278486 TI - Development of a computer-aided diagnostic scheme for detection of interval changes in successive whole-body bone scans. AB - Bone scintigraphy is the most frequent examination among various diagnostic nuclear medicine procedures. It is a well-established imaging modality for the diagnosis of osseous metastasis and for monitoring osseous tumor response to chemotherapy and radiation therapy. Although the sensitivity of bone scan examinations for detection of bone abnormalities has been considered to be relatively high, it is time consuming to identify multiple lesions such as bone metastases of prostate and breast cancers. In addition, it is very difficult to detect subtle interval changes between two successive abnormal bone scans, because of variations in patient conditions, the accumulation of radioisotopes during each examination, and the image quality of gamma cameras. Therefore, we developed a new computer-aided diagnostic (CAD) scheme for the detection of interval changes in successive whole-body bone scans by use of a temporal subtraction image which was obtained with a nonlinear image-warping technique. We carried out 58 pairs of successive bone scans in which each scan included both posterior and anterior views. We determined 107 "gold-standard" interval changes among the 58 pairs based on the consensus of three radiologists. Our computerized scheme consisted of seven steps, i.e., initial image density normalization on each image, image matching for the paired images, temporal subtraction by use of the nonlinear image-warping technique, initial detection of interval changes by use of temporal-subtraction images, image feature extraction of candidates of interval changes, rule-based tests by use of 16 image features for removing some false positives, and display of the computer output for identified interval changes. One hundred seven gold standard interval changes included 71 hot lesions (uptake was increased compared with the previous scan, or there was new uptake in the current scan) and 36 cold lesions (uptake was decreased or disappeared) for anterior and posterior views. The overall sensitivity in the detection of interval changes, including both hot and cold lesions evaluated by use of the resubstitution and the leave-one-case-out methods, were 95.3%, with 5.97 false positives per view, and 83.2% with 6.02, respectively. The temporal subtraction image for successive whole-body bone scans has the potential to enhance the interval changes between two images, which also can be quantified. Furthermore, the CAD scheme for the detection of interval changes by use of temporal subtraction images would be useful in assisting radiologists' interpretation on successive bone scan images. PMID- 17278487 TI - Dosimetric prerequisites for routine clinical use of photon emitting brachytherapy sources with average energy higher than 50 kev. AB - This paper presents the recommendations of the American Association of Physicists in Medicine (AAPM) and the European Society for Therapeutic Radiology and Oncology (ESTRO) on the dosimetric parameters to be characterized, and dosimetric studies to be performed to obtain them, for brachytherapy sources with average energy higher than 50 keV that are intended for routine clinical use. In addition, this document makes recommendations on procedures to be used to maintain vendor source strength calibration accuracy. These recommendations reflect the guidance of the AAPM and the ESTRO for its members, and may also be used as guidance to vendors and regulatory agencies in developing good manufacturing practices for sources used in routine clinical treatments. PMID- 17278488 TI - Comparison of the epson expression 1680 flatbed and the vidar VXR-16 dosimetry PRO film scanners for use in IMRT dosimetry using gafchromic and radiographic film. AB - Intensity-modulated radiotherapy (IMRT) treatment plan verification is often done using Kodak EDR2 film and a Vidar Dosimetry PRO film digitizer. However, since many hospitals are moving towards a filmless environment, access to a film processor may not be available. Therefore, we have investigated a newly available Gafchromic EBT film for IMRT dosimetry. Planar IMRT dose distributions are delivered to both EBT and EDR2 film and scanned with the Vidar VXR-16 as well as an Epson Expression 1680 flatbed scanner. The measured dose distributions are then compared to those calculated with a Pinnacle treatment planning system. The IMRT treatments consisted of 7-9 6 MV beams for treatment of prostate, head and neck, and a few other sites. The films were analyzed using FilmQATM (3cognition LLC) software. Comparisons between measured and calculated dose distributions are reported as dose difference (DD) (pixels within +/-5%), distance to agreement (DTA) (3 mm), as well as gamma values (y) (dose= +/-3%, dist. =2 mm). Using EDR2 with the Vidar scanner is an established technique and agreement between calculated and measured dose distributions was better than 90% in all indices (DD, DTA, and gamma). However, agreement with calculations deteriorated reaching the lower 80% for EBT film scans with the Vidar scanner in logarithmic mode. The EBT Vidar scans obtained in linear mode showed an improved agreement to the upper 80% range, but artifacts were still observed across the scan. These artifacts were very distinct in all EBT scans and can be attributed to the way the film is transported through the scanner. In the Epson scanner both films are rigidly immobilized and the light source scans over the film. It was found that the Epson scanner performed equally well with both types of film giving agreement to better than 90% in all indices. PMID- 17278489 TI - Multiple-estimate monte carlo calculation of the dose rate constant for a cesium 131 interstitial brachytherapy seed. AB - The purpose of this study was to calculate a more accurate dose rate constant for the 131Cs (model CS-1, IsoRay Medical, Inc., Richland, WA) interstitial brachytherapy seed. Previous measurements of the dose rate constant for this seed have been reported by others with incongruity. Recent direct measurements by thermoluminescence dosimetry and by gamma-ray spectroscopy were about 15% greater than earlier thermoluminescence dosimetry measurements. Therefore, we set about to calculate independent values by a Monte Carlo approach that combined three estimates as a consistency check, and to quantify the computational uncertainty. The calculated dose rate constant for the 131Cs seed was 1.040 cGy h(-1) U(-1) for an ionization chamber model and 1.032 cGy h(-1) U(-1) for a circular ring model. A formal value of 2.2% uncertainty was calculated for both values. The range of our multiestimate values were from 1.032 to 1.061 cGy h(-1) U(-1). We also modeled three 125I seeds with known dose rate constants to test the accuracy of this study's approach. PMID- 17278490 TI - Automated matching and segmentation of lymphoma on serial CT examinations. AB - In patients with lymphoma, identification and quantification of the tumor extent on serial CT examinations is critical for assessing tumor response to therapy. In this paper, we present a computer method to automatically match and segment lymphomas in follow-up CT images. The method requires that target lymph nodes in baseline CT images be known. A fast, approximate alignment technique along the x, y, and axial directions is developed to provide a good initial condition for the subsequent fast free form deformation (FFD) registration of the baseline and the follow-up images. As a result of the registration, the deformed lymph node contours from the baseline images are used to automatically determine internal and external markers for the marker-controlled watershed segmentation performed in the follow-up images. We applied this automated registration and segmentation method retrospectively to 29 lymph nodes in 9 lymphoma patients treated in a clinical trial at our cancer center. A radiologist independently delineated all lymph nodes on all slices in the follow-up images and his manual contours served as the "gold standard" for evaluation of the method. Preliminary results showed that 26/29 (89.7%) lymph nodes were correctly matched; i.e., there was a geometrical overlap between the deformed lymph node from the baseline and its corresponding mass in the follow-up images. Of the matched 26 lymph nodes, 22 (84.6%) were successfully segmented; for these 22 lymph nodes, several metrics were calculated to quantify the method's performance. Among them, the average distance and the Hausdorff distance between the contours generated by the computer and those generated by the radiologist were 0.9 mm (stdev. 0.4 mm) and 3.9 mm (stdev. 2.1 mm), respectively. PMID- 17278491 TI - MCNP-based computational model for the Leksell gamma knife. AB - We have focused on the usage of MCNP code for calculation of Gamma Knife radiation field parameters with a homogenous polystyrene phantom. We have investigated several parameters of the Leksell Gamma Knife radiation field and compared the results with other studies based on EGS4 and PENELOPE code as well as the Leksell Gamma Knife treatment planning system Leksell GammaPlan (LGP). The current model describes all 201 radiation beams together and simulates all the sources in the same time. Within each beam, it considers the technical construction of the source, the source holder, collimator system, the spherical phantom, and surrounding material. We have calculated output factors for various sizes of scoring volumes, relative dose distributions along basic planes including linear dose profiles, integral doses in various volumes, and differential dose volume histograms. All the parameters have been calculated for each collimator size and for the isocentric configuration of the phantom. We have found the calculated output factors to be in agreement with other authors' works except the case of 4 mm collimator size, where averaging over the scoring volume and statistical uncertainties strongly influences the calculated results. In general, all the results are dependent on the choice of the scoring volume. The calculated linear dose profiles and relative dose distributions also match independent studies and the Leksell GammaPlan, but care must be taken about the fluctuations within the plateau, which can influence the normalization, and accuracy in determining the isocenter position, which is important for comparing different dose profiles. The calculated differential dose volume histograms and integral doses have been compared with data provided by the Leksell GammaPlan. The dose volume histograms are in good agreement as well as integral doses calculated in small calculation matrix volumes. However, deviations in integral doses up to 50% can be observed for large volumes such as for the total skull volume. The differences observed in treatment of scattered radiation between the MC method and the LGP may be important in this case. We have also studied the influence of differential direction sampling of primary photons and have found that, due to the anisotropic sampling, doses around the isocenter deviate from each other by up to 6%. With caution about the details of the calculation settings, it is possible to employ the MCNP Monte Carlo code for independent verification of the Leksell Gamma Knife radiation field properties. PMID- 17278492 TI - Biological dose volume histograms during conformal hypofractionated accelerated radiotherapy for prostate cancer. AB - Radiobiological data suggest that prostate cancer has a low alpha/beta ratio. Large radiotherapy fractions may, therefore, prove more efficacious than standard radiotherapy, while radiotherapy acceleration should further improve control rates. This study describes the radiobiology of a conformal hypofractionated accelerated radiotherapy scheme for the treatment of high risk prostate cancer. Anteroposterior fields to the pelvis deliver a daily dose of 2.7 Gy, while lateral fields confined to the prostate and seminal vesicles deliver an additional daily dose of 0.7 Gy. Radiotherapy is accomplished within 19 days (15 fractions). Dose volume histograms, calculated for tissue specific alpha/beta ratios and time factors, predict a high biological dose to the prostate and seminal vesicles (77-93 Gy). The biological dose to normal pelvic tissues is maintained at standard levels. Radiobiological dosimetry suggests that, using hypofractionated and accelerated radiotherapy, high biological radiation dose can be given to the prostate without overdosing normal tissues. PMID- 17278493 TI - Ambient illumination revisited: a new adaptation-based approach for optimizing medical imaging reading environments. AB - Ambient lighting in soft-copy reading rooms is currently kept at low values to preserve contrast rendition in the dark regions of a medical image. Low illuminance levels, however, create inadequate viewing conditions and may also cause eye strain. This eye strain may be potentially attributed to notable variations in the luminance adaptation state of the reader's eyes when moving the gaze intermittently between the brighter display and darker surrounding surfaces. This paper presents a methodology to minimize this variation and optimize the lighting conditions of reading rooms by exploiting the properties of liquid crystal displays (LCDs) with low diffuse reflection coefficients and high luminance ratio. First, a computational model was developed to determine a global luminance adaptation value, Ladp, when viewing a medical image on display. The model is based on the diameter of the pupil size, which depends on the luminance of the observed object. Second, this value was compared with the luminance reflected off surrounding surfaces, Ls, under various conditions of room illuminance, E, different values of diffuse reflection coefficients of surrounding surfaces, Rs, and calibration settings of a typical LCD. The results suggest that for typical luminance settings of current LCDs, it is possible to raise ambient illumination to minimize differences in eye adaptation, potentially reducing visual fatigue while also complying with the TG18 specifications for controlled contrast rendition. Specifically, room illumination in the 75-150 lux range and surface diffuse reflection coefficients in the practical range of 0.13 0.22 sr(-1) provide an ideal setup for typical LCDs. Future LCDs with lower diffuse reflectivity and with higher inherent luminance ratios can provide further improvement of ergonomic viewing conditions in reading rooms. PMID- 17278494 TI - Synchronized dynamic dose reconstruction. AB - Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined. PMID- 17278495 TI - Dose response of BaFBrl: Eu2+ storage phosphor plates exposed to megavoltage photon beams. AB - The BaFBrI:Eu2+ storage phosphor plate (SPP) is a reusable radiation image detector, widely used in diagnostic computed radiography, x-ray crystallography and radioactive tracer studies. When exposed to ionizing radiation, the SPP stores a latent image until it is scanned with a red reading laser which causes blue photostimulated luminescent (PSL) photons to be emitted. The mechanism of formation of the latent image is still poorly understood, especially for megavoltage photon beams. In order to gain insight into this mechanism and aid applications to high-energy beam dosimetry, the authors have directly determined the SPP generation efficiency, W, the energy required to produce one quantum of emitted PSL when it is irradiated by 60Co and 6 MV photon beams. This was done in four steps: 1. The SPP, in a water-equivalent plastic (WEP) phantom, was exposed to a 60Co or 6 MV beam, which had been calibrated to give a known absorbed dose to water in a water phantom at the position of the sensitive layer of the SPP. 2. Monte Carlo simulations were used to calculate the ratio of the dose to the sensitive layer in the WEP phantom to the dose to water at the same position in a water phantom. 3. A bleaching experiment was used to determine the number of photons emitted by a plate given a known dose. 4. The generation efficiency was calculated from the number of photons and the dose. This method is much more direct than previous calculations for kilovoltage x-ray beams based on quantum noise analysis. W was found, within experimental uncertainty, to be 190 eV for 60Co and 160 eV for 6 MV, independent of dose. The values for kilovoltage x-ray beams determined previously agree, within their large uncertainty, with these values for megavoltage beams. PMID- 17278496 TI - Absorption spectroscopy of EBT model GAFCHROMIC film. AB - The introduction of radiochromic films has solved some of the problems associated with conventional 2D radiation detectors. Their high spatial resolution, low energy dependence, and near-tissue equivalence make them ideal for measurement of dose distributions in radiation fields with high dose gradients. Precise knowledge of the absorption spectra of these detectors can help to develop more suitable optical densitometers and potentially extend the use of these films to other areas such as the measurement of the radiation beam spectral information. The goal of this study is to present results of absorption spectra measurements for the new GAFCHROMIC film, EBT type, exposed to 6 MV photon beam in the dose range from 0 to 6 Gy. Spectroscopic analysis reveals that in addition to the two main absorption peaks, centered at around 583 and 635 nm, the absorption spectrum in the spectral range from 350 to 800 nm contains six more absorption bands. Comparison of the absorption spectra reveals that previous HD-810, MD-55, as well as HS GAFCHROMIC film models, have nearly the same sensitive layer base material, whereas the new EBT model, GAFCHROMIC film has a different composition of its sensitive layer. We have found that the two most prominent absorption bands in EBT model radiochromic film do not change their central wavelength position with change in a dose deposited to the film samples. PMID- 17278497 TI - Comparison between a built-in "dual side" chest imaging device and a standard "single side" CR. AB - An integrated readout computed radiography system (Fuji XU-D1) incorporating dual side imaging plates (ST-55BD) was analyzed in terms of modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) for standard beam qualities RQA 9 and RQA 5. NPS and DQE were assessed using a detector entrance air kerma consistent with clinical practice for chest radiography. Similar investigation was performed on a standard reader (Fuji FCR 5000) using single-side imaging plates (ST-VI). Negligible differences were found between the MTFs of the two imaging systems for RQA 9, whereas for RQA 5 the single-side system exhibited slightly superior MTF. Regarding noise response, the dual-side system turned out to be better performing for both beam qualities over a wide range of frequencies. For RQA 9, at 8 microGy, the DQE of the dual-side system was moderately higher over the whole frequency range, whereas for RQA 5, at 10 microGy, significant improvement was found at low- and midrange frequencies. As an example, at 1 cycle/mm, the following improvements in the DQE of the dual-side system were observed: +22% (RQA 9, at 8 microGy), +50% (RQA 9, at 30 microGy), and +45% (RQA 5, at 10 microGy). PMID- 17278499 TI - Evaluation of information-theoretic similarity measures for content-based retrieval and detection of masses in mammograms. AB - The purpose of this study was to evaluate image similarity measures employed in an information-theoretic computer-assisted detection (IT-CAD) scheme. The scheme was developed for content-based retrieval and detection of masses in screening mammograms. The study is aimed toward an interactive clinical paradigm where physicians query the proposed IT-CAD scheme on mammographic locations that are either visually suspicious or indicated as suspicious by other cuing CAD systems. The IT-CAD scheme provides an evidence-based, second opinion for query mammographic locations using a knowledge database of mass and normal cases. In this study, eight entropy-based similarity measures were compared with respect to retrieval precision and detection accuracy using a database of 1820 mammographic regions of interest. The IT-CAD scheme was then validated on a separate database for false positive reduction of progressively more challenging visual cues generated by an existing, in-house mass detection system. The study showed that the image similarity measures fall into one of two categories; one category is better suited to the retrieval of semantically similar cases while the second is more effective with knowledge-based decisions regarding the presence of a true mass in the query location. In addition, the IT-CAD scheme yielded a substantial reduction in false-positive detections while maintaining high detection rate for malignant masses. PMID- 17278498 TI - Optimization of dual-energy imaging systems using generalized NEQ and imaging task. AB - Dual-energy (DE) imaging is a promising advanced application of flat-panel detectors (FPDs) with a potential host of applications ranging from thoracic and cardiac imaging to interventional procedures. The performance of FPD-based DE imaging systems is investigated in this work by incorporating the noise-power spectrum associated with overlying anatomical structures ("anatomical noise" modeled according to a 1/f characteristic) into descriptions of noise-equivalent quanta (NEQ) to yield the generalized NEQ (GNEQ). Signal and noise propagation in the DE imaging chain is modeled by cascaded systems analysis. A Fourier-based description of the imaging task is integrated with the GNEQ to yield a detectability index used as an objective function for optimizing DE image reconstruction, allocation of dose between low- and high-energy images, and selection of low- and high-kVp. Optimal reconstruction and acquisition parameters were found to depend on dose; for example, optimal kVp varied from [60/150] kVp at typical radiographic dose levels (approximately 0.5 mGy entrance surface dose, ESD) but increased to [90/150] kVp at high dose (ESD approximately 5.0 mGy). At very low dose (ESD approximately 0.05 mGy), detectability index indicates an optimal low-energy technique of 60 kVp but was largely insensitive to the choice of high-kVp in the range 120-150 kVp. Similarly, optimal dose allocation, defined as the ratio of low-energy ESD and the total ESD, varied from 0.2 to 0.4 over the range ESD=(0.05-5.0) mGy. Furthermore, two applications of the theoretical framework were explored: (i) the increase in detectability for DE imaging compared to conventional radiography; and (ii) the performance of single-shot vs double-shot DE imaging, wherein the latter is found to have a DQE approximately twice that of the former. Experimental and theoretical analysis of GNEQ and task based detectability index provides a fundamental understanding of the factors governing DE imaging performance and offers a framework for system design and optimization. PMID- 17278500 TI - Robust experiment design for estimating myocardial beta adrenergic receptor concentration using PET. AB - Myocardial beta adrenergic receptor (beta-AR) concentration can substantially decrease in congestive heart failure and significantly increase in chronic volume overload, such as in severe aortic valve regurgitation. Positron emission tomography (PET) with an appropriate ligand-receptor model can be used for noninvasive estimation of myocardial beta-AR concentration in vivo. An optimal design of the experiment protocol, however, is needed for sufficiently precise estimates of beta-AR concentration in a heterogeneous population. Standard methods of optimal design do not account for a heterogeneous population with a wide range of beta-AR concentrations and other physiological parameters and consequently are inadequate. To address this, we have developed a methodology to design a robust two-injection protocol that provides reliable estimates of myocardial beta-AR concentration in normal and pathologic states. A two-injection protocol of the high affinity beta-AR antagonist [18F]-(S)-fluorocarazolol was designed based on a computer-generated (or synthetic) population incorporating a wide range of beta-AR concentrations. Timing and dosage of the ligand injections were optimally designed with minimax criterion to provide the least bad beta-AR estimates for the worst case in the synthetic population. This robust experiment design for PET was applied to experiments with pigs before and after beta-AR upregulation by chemical sympathectomy. Estimates of beta-AR concentration were found by minimizing the difference between the model-predicted and experimental PET data. With this robust protocol, estimates of beta-AR concentration showed high precision in both normal and pathologic states. The increase in beta-AR concentration after sympathectomy predicted noninvasively with PET is consistent with the increase shown by in vitro assays in pig myocardium. A robust experiment protocol was designed for PET that yields reliable estimates of beta-AR concentration in a population with normal and pathologic states. This methodology is applicable in general to optimal estimation of parameters in heterogeneous populations. PMID- 17278501 TI - Development of dosimetry using detectors of diagnostic digital radiography systems. AB - Dosimetry using an imaging plate (IP) of computed radiography (CR) systems was developed for quality control of output of the x-ray equipment. Sensitivity index, or the S number, of the CR systems was used for estimating exposure dose under the routine condition: exposure dose from 1.0 to 1.0 x 10(2) microC kg(-1), tube voltages from 50 to 120 kV, and added filtration from 0 to 4.0 mm Al. The IP was calibrated by using a 6 cc ionization chamber having traceability to the National Standard Ionization Chamber. The uncertainty concerning the fading effect was suppressed less than 1.9% by reading the latent image 4 min+/-5 s after irradiation at the room temperature 25.9+/-1.0 degrees C. The S number decreased linearly on the logarithmic graph regardless of the beam quality as exposure dose increased. The relationship between the exposure dose (E) and the S number was fitted by the equation E=a' X S(-b). The coefficient a' decreased when the added filtration and the tube voltage were increased. The coefficient b was 0.977+/-0.007 in all beam qualities. The dosimetry using the IP and the equation can estimate the exposure dose in a range from 9.0 x 10(-2) to 5.0 microC kg(-1) within an uncertainty of +/-5% required by the Japanese Industry Standard. This dose range partially included the doses under routine condition. The doses between 1.0 and 1.0 x 10(2) microC kg(-1) under the routine condition can be shifted to the 5% region by using an absorber. The IP dosimetry is applicable to the quality control of the CR systems. PMID- 17278502 TI - Calculation of lateral buildup ratio using Monte Carlo simulation for electron radiotherapy. AB - Monte Carlo simulation was used to calculate the lateral buildup ratio (LBR) used in estimating the percentage depth dose (PDD) and dose per monitor unit for an irregular shaped cutout field in electron radiotherapy. Monte Carlo code BEAMnrc/EGSnrc was used to build a simulation model for a Varian 21 EX linear accelerator producing clinical electron beams with energies of 4, 6, 9, 12, and 16 MeV. The model is optimized by adjusting the incident electron energy within the Monte Carlo simulation so that the calculated PDD curves agree with the measurement within +/-2%. The LBR is calculated from the PDD curves for different diameters of circular cutouts. Although Monte Carlo simulation requires a longer time to create a LBR database compared to measurement using scanning water tank and dosimeter, the simulation models for different electron energies, applicators, and cutouts are very similar. As the calculations can be carried out in a batch mode automatically run by a computer, human efforts in carrying out measurements in the treatment room and fabricating the circular cutouts in the mold room are greatly saved. Moreover, the simulation avoids human error in the experimental setup and can better handle the electron scattering affecting accuracy in the measurement. Using Monte Carlo simulation to calculate the LBR is proved to be useful in the commissioning of the electron beams for electron radiotherapy. PMID- 17278503 TI - Depth absorbed dose and LET distributions of therapeutic 1H, 4He, 7Li, and 12C beams. AB - The depth absorbed dose and LET (linear energy transfer) distribution of different ions of clinical interest such as 1H, 4He, 7Li, and 12C ions have been investigated using the Monte Carlo code SHIELD-HIT. The energies of the projectiles correspond to ranges in water and soft tissue of approximately 260 mm. The depth dose distributions of the primary particles and their secondaries have been calculated and separated with regard to their low and high LET components. A LET value below 10 eV/nm can generally be regarded as low LET and sparsely ionizing like electrons and photons. The high LET region may be assumed to start at 20 eV/nm where on average two double-strand breaks can be formed when crossing the periphery of a nucleosome, even though strictly speaking the LET limits are not sharp and ought to vary with the charge and mass of the ion. At the Bragg peak of a monoenergetic high energy proton beam, less than 3% of the total absorbed dose is comprised of high LET components above 20 eV/nm. The high LET contribution to the total absorbed dose in the Bragg peak is significantly larger with increasing ion charge as a natural result of higher stopping power and lower range straggling. The fact that the range straggling and multiple scattering are reduced by half from hydrogen to helium increases the possibility to accurately deposit only the high LET component in the tumor with negligible dose to organs at risk. Therefore, the lateral penumbra is significantly improved and the higher dose gradients of 7Li and 12C ions both longitudinally and laterally will be of major advantage in biological optimized radiation therapy. With increasing charge of the ion, the high LET absorbed dose in the beam entrance and the plateau regions where healthy normal tissues are generally located is also increased. The dose distribution of the high LET components in the 7Li beam is only located around the Bragg peak, characterized by a Gaussian type distribution. Furthermore, the secondary particles produced by high energy 7Li ions in tissuelike media have mainly low LET character both in front of and beyond the Bragg peak. PMID- 17278504 TI - Dose contributions from large-angle scattered particles in therapeutic carbon beams. AB - In carbon therapy, doses at center of spread-out Bragg peaks depend on field size. For a small field of 5 x 5 cm2, the central dose reduces to 96% of the central dose for the open field in case of 400 MeV/n carbon beam. Assuming the broad beam injected to the water phantom is made up of many pencil beams, the transverse dose distribution can be reconstructed by summing the dose distribution of the pencil beams. We estimated dose profiles of this pencil beam through measurements of dose distributions of broad uniform beams blocked half of the irradiation fields. The dose at a distance of a few cm from the edge of the irradiation field reaches up to a few percent of the central dose. From radiation quality measurements of this penumbra, the large-angle scattered particles were found to be secondary fragments which have lower LET than primary carbon beams. Carbon ions break up in beam modifying devices or in water phantom through nuclear interaction with target nuclei. The angular distributions of these fragmented nuclei are much broader than those of primary carbon particles. The transverse dose distribution of the pencil beam can be approximated by a function of the three-Gaussian form. For a simplest case of mono-energetic beam, contributions of the Gaussian components which have large mean deviations become larger as the depth in the water phantom increases. PMID- 17278505 TI - Technical note: a deformable phantom for dynamic modeling in radiation therapy. AB - A deformable phantom was developed to aid in quality assurance for dynamic imaging and targeting techniques in radiation therapy. Made of simple materials combined with standard components for imaging and motion experiments, this phantom can be relatively easily constructed and used for both diagnostic imaging and dosimetry. Repeat imaging studies indicate that the phantom meets criteria of relative attenuation, deformation, and reproducibility of configuration, necessary for quality assurance of radiographic and tomographic targeting. PMID- 17278506 TI - Evaluation of clinical margins via simulation of patient setup errors in prostate IMRT treatment plans. AB - This work evaluates: (i) the size of random and systematic setup errors that can be absorbed by 5 mm clinical target volume (CTV) to planning target volume (PTV) margins in prostate intensity modulated radiation therapy (IMRT); (ii) agreement between simulation results and published margin recipes; and (iii) whether shifting contours with respect to a static dose distribution accurately predicts dose coverage due to setup errors. In 27 IMRT treatment plans created with 5 mm CTV-to-PTV margins, random setup errors with standard deviations (SDs) of 1.5, 3, 5 and 10 mm were simulated by fluence convolution. Systematic errors with identical SDs were simulated using two methods: (a) shifting the isocenter and recomputing dose (isocenter shift), and (b) shifting patient contours with respect to the static dose distribution (contour shift). Maximum tolerated setup errors were evaluated such that 90% of plans had target coverage equal to the planned PTV coverage. For coverage criteria consistent with published margin formulas, plans with 5 mm margins were found to absorb combined random and systematic SDs = 3 mm. Published recipes require margins of 8-10 mm for 3 mm SDs. For the prostate IMRT cases presented here a 5 mm margin would suffice, indicating that published recipes may be pessimistic. We found significant errors in individual plan doses given by the contour shift method. However, dose population plots (DPPs) given by the contour shift method agreed with the isocenter shift method for all structures except the nodal CTV and small bowel. For the nodal CTV, contour shift DPP differences were due to the structure moving outside the patient. Small bowel DPP errors were an artifact of large relative differences at low doses. Estimating individual plan doses by shifting contours with respect to a static dose distribution is not recommended. However, approximating DPPs is acceptable, provided care is taken with structures such as the nodal CTV which lie close to the surface. PMID- 17278507 TI - Characterization of the ADII-33 diamond detector. AB - Dosimetry characteristics of the ADII-33 diamond detector were investigated. Sensitivity, stability, bias voltage, hardening, dose rate, energy dependence, and spatial resolution were examined. Current generated in the detector was found to be proportional to the bias voltage applied to the detector with stability degrading as a function of the bias voltage. The average current increased with increasing bias voltage. The statistical fluctuation in current was less than 0.3% regardless of the applied bias voltage. The optimal bias voltage, at which the current uncertainty is negligible, was found to be 125+/-25 V. The detector was hardened up to 85 kGy without significant degradation in output signal. A sub linearity in the current as a function of dose rate was observed when the dose rate varied from 600.0 to 11.1 cGy/min. A fitting parameter of delta=0.978 was observed in the power relationship of IinfinityDdelta. When comparing the diamond detector readings to corrected ion chamber readings over a wide energy range of electron beams, differences of only 0.2% were observed suggesting no energy dependence for electron beam. PDD curves for a 10 x 10 cm2 field for 6 and 20 MV photon beams measured with the diamond detector and the farmer type ion chamber were also compared and they closely agreed up to a depth of 14 cm. Beyond a depth of 14 cm, diamond detector starts to overestimate the PDD curve reaching difference of 1.90% and 1.0% at 18 cm depth for 6 and 20 MV, respectively, to those values measured with the ion chamber. The diamond detector presents slightly better spatial resolution than the Exradin A16 microchamber. We conclude that at the optimal bias voltage, this new diamond detector is stable and the uncertainties in the current will not affect its suitability for clinical use. If compared against a calibrated ion chamber to correct any energy and dose rate dependence and considering any radiation damage effect, this diamond detector can be used to measure absolute and relative dose. PMID- 17278508 TI - Computation of the glandular radiation dose in digital tomosynthesis of the breast. AB - Tomosynthesis of the breast is currently a topic of intense interest as a logical next step in the evolution of digital mammography. This study reports on the computation of glandular radiation dose in digital tomosynthesis of the breast. Previously, glandular dose estimations in tomosynthesis have been performed using data from studies of radiation dose in conventional planar mammography. This study evaluates, using Monte Carlo methods, the normalized glandular dose (DgN) to the breast during a tomosynthesis study, and characterizes its dependence on breast size, tissue composition, and x-ray spectrum. The conditions during digital tomosynthesis imaging of the breast were simulated using a computer program based on the Geant4 toolkit. With the use of simulated breasts of varying size, thickness and tissue composition, the DgN to the breast tissue was computed for varying x-ray spectra and tomosynthesis projection angle. Tomosynthesis projections centered about both the cranio-caudal (CC) and medio-lateral oblique (MLO) views were simulated. For each projection angle, the ratio of the glandular dose for that projection to the glandular dose for the zero degree projection was computed. This ratio was denoted the relative glandular dose (RGD) coefficient, and its variation under different imaging parameters was analyzed. Within mammographic energies, the RGD was found to have a weak dependence on glandular fraction and x-ray spectrum for both views. A substantial dependence on breast size and thickness was found for the MLO view, and to a lesser extent for the CC view. Although RGD values deviate substantially from unity as a function of projection angle, the RGD averaged over all projections in a complete tomosynthesis study varies from 0.91 to 1.01. The RGD results were fit to mathematical functions and the resulting equations are provided. PMID- 17278510 TI - Rigid 2D/3D slice-to-volume registration and its application on fluoroscopic CT images. AB - Registration of single slices from FluoroCT, CineMR, or interventional magnetic resonance imaging to three dimensional (3D) volumes is a special aspect of the two-dimensional (2D)/3D registration problem. Rather than digitally rendered radiographs (DRR), single 2D slice images obtained during interventional procedures are compared to oblique reformatted slices from a high resolution 3D scan. Due to the lack of perspective information and the different imaging geometry, convergence behavior differs significantly from 2D/3D registration applications comparing DRR images with conventional x-ray images. We have implemented a number of merit functions and local and global optimization algorithms for slice-to-volume registration of computed tomography (CT) and FluoroCT images. These methods were tested on phantom images derived from clinical scans for liver biopsies. Our results indicate that good registration accuracy in the range of 0.50 and 1.0 mm is achievable using simple cross correlation and repeated application of local optimization algorithms. Typically, a registration took approximately 1 min on a standard personal computer. Other merit functions such as pattern intensity or normalized mutual information did not perform as well as cross correlation in this initial evaluation. Furthermore, it appears as if the use of global optimization algorithms such as simulated annealing does not improve reliability or accuracy of the registration process. These findings were also confirmed in a preliminary registration study on five clinical scans. These experiments have, however, shown that a strict breath-hold protocol is inevitable when using rigid registration techniques for lesion localization in image-guided biopsy retrieval. Finally, further possible applications of slice-to-volume registration are discussed. PMID- 17278509 TI - How extensive of a 4D dataset is needed to estimate cumulative dose distribution plan evaluation metrics in conformal lung therapy? AB - The purpose of this study was to investigate the number of intermediate states required to adequately approximate the clinically relevant cumulative dose to deforming/moving thoracic anatomy in four-dimensional (4D) conformal radiotherapy that uses 6 MV photons to target tumors. Four patients were involved in this study. For the first three patients, computed tomography images acquired at exhale and inhale were available; they were registered using B-spline deformation model and the computed transformation was further used to simulate intermediate states between exhale and inhale. For the fourth patient, 4D-acquired, phase sorted datasets were available and each dataset was registered with the exhale dataset. The exhale-inhale transformation was also used to simulate intermediate states in order to compare the cumulative doses computed using the actual and the simulated datasets. Doses to each state were calculated using the Dose Planning Method (DPM) Monte Carlo code and dose was accumulated for scoring on the exhale anatomy via the transformation matrices for each state and time weighting factors. Cumulative doses were estimated using increasing numbers of intermediate states and compared to simpler scenarios such as a "2-state" model which used only the exhale and inhale datasets or the dose received during the average phase of the breathing cycle. Dose distributions for each modeled state as well as the cumulative doses were assessed using dose volume histograms and several treatment evaluation metrics such as mean lung dose, normal tissue complication probability, and generalized uniform dose. Although significant "point dose" differences can exist between each breathing state, the differences decrease when cumulative doses are considered, and can become less significant yet in terms of evaluation metrics depending upon the clinical end point. This study suggests that for certain "clinical" end points of importance for lung cancer, satisfactory predictions of accumulated total dose to be received by the distorting anatomy can be achieved by calculating the dose to but a few (or even simply the average) phases of the breathing cycle. PMID- 17278511 TI - An iterative three-dimensional electron density imaging algorithm using uncollimated compton scattered x rays from a polyenergetic primary pencil beam. AB - X-ray film-screen mammography is currently the gold standard for detecting breast cancer. However, one disadvantage is that it projects a three-dimensional (3D) object onto a two-dimensional (2D) image, reducing contrast between small lesions and layers of normal tissue. Another limitation is its reduced sensitivity in women with mammographically dense breasts. Computed tomography (CT) produces a 3D image yet has had a limited role in mammography due to its relatively high dose, low resolution, and low contrast. As a first step towards implementing quantitative 3D mammography, which may improve the ability to detect and specify breast tumors, we have developed an analytical technique that can use Compton scatter to obtain 3D information of an object from a single projection. Imaging material with a pencil beam of polychromatic x rays produces a characteristic scattered photon spectrum at each point on the detector plane. A comparable distribution may be calculated using a known incident x-ray energy spectrum, beam shape, and an initial estimate of the object's 3D mass attenuation and electron density. Our iterative minimization algorithm changes the initially arbitrary electron density voxel matrix to reduce regular differences between the analytically predicted and experimentally measured spectra at each point on the detector plane. The simulated electron density converges to that of the object as the differences are minimized. The reconstruction algorithm has been validated using simulated data produced by the EGSnrc Monte Carlo code system. We applied the imaging algorithm to a cylindrically symmetric breast tissue phantom containing multiple inhomogeneities. A preliminary ROC analysis scores greater than 0.96, which indicate that under the described simplifying conditions, this approach shows promise in identifying and localizing inhomogeneities which simulate 0.5 mm calcifications with an image voxel resolution of 0.25 cm and at a dose comparable to mammography. PMID- 17278512 TI - Using a priori structural information from magnetic resonance imaging to investigate the feasibility of prostate diffuse optical tomography and spectroscopy: a simulation study. AB - Implementation of diffuse optical tomography (DOT) for prostate cancer is challenging because the prostate is a deep-seated organ. We investigated whether diffuse optical tomography (DOT) and spectroscopy could be applied to monitor the physiology of prostate cancer using a small probe that could be placed endorectally. We manually segmented the prostate, the intraprostatic tumor, and the rectum using data from endorectal magnetic resonance imaging. These structures were reconstructed and meshed with tetrahedral finite elements in three dimensions. A 2 x 4 cm probe that has ten sources and 52 detectors were placed to face the anterior wall of the rectum in our simulation. Optical properties of the organs were obtained from the literature in the near infrared regime. Diffusion approximation was used to simulate photon migration with finite element method. Five wavelengths were used to simulate tissue absorption with realistic water, oxy- and deoxyhaemoglobin concentrations in the prostate. We combined a global search based on genetic algorithm with gradient-driven local search methods to fit the simulated data. Our results suggest that the optical properties and the concentrations of the chromophores of the prostate and the prostate cancer can be reliably recovered from the measurements using an endorectal probe. Prostate DOT is worth further investigation for clinical application. PMID- 17278513 TI - Evaluation of the spatial resolution characteristics of a cone-beam breast CT scanner. AB - The purpose of this study was to examine the spatial resolution of a prototype pendant-geometry cone-beam breast computed tomography (CT) system. Modulation transfer functions (MTFs) of the reconstructed image in the coronal (x and y) plane were computed as a function of the cone angle, the radial distance from the axis of rotation, the size of the reconstruction matrix, the back-projection filter used, and the number of projections acquired for the reconstruction. The results show that the cone angle and size of the reconstruction matrix have minimal impact on the MTF, while the MTF degraded radially from the axis of rotation (from 0.76 at 2.6 mm from axis of rotation down to 0.37 at 76.9 mm from axis of rotation at f=0.5 mm(-1)). The Ramp reconstruction filter increases the MTF near the axis of rotation relative to the Shepp-Logan filter, while an increase in the number of projections from 500 to 1000 increased the MTF near the periphery of the reconstructed image. The MTF in the z direction (anterior posterior direction) was also evaluated. The z-direction MTF values tend to be higher when compared to the coronal MTF (0.85 at f =0.5 mm(-1)), and tend to be very constant throughout the coronal plane direction. The results suggest that an increase in the MTF for the prototype breast CT system is possible by optimizing various scanning and reconstruction parameters. PMID- 17278514 TI - A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy. AB - We have developed a comprehensive theoretical model for rigorously describing the spatial and temporal dynamics of oxygen (3O2) consumption and transport and microscopic photodynamic dose deposition during photodynamic therapy (PDT) in vivo. Previously published models have been improved by considering perfused vessels as a time-dependent 3O2 source and linking the 3O2 concentration in the vessel to that within the tissue through the Hill equation. The time-dependent photochemical 3O2 consumption rate incorporates sensitizer photobleaching effects and an experimentally determined initially nonuniform photosensitizer distribution. The axial transport of 3O2 is provided for in the capillaries and in the surrounding tissue. A self-sensitized singlet oxygen (1O2)-mediated bleaching mechanism and the measured, initially nonuniform distribution of mesotetrahydroxyphenyl chlorin at 3 h after intravascular administration were used to demonstrate the capabilities of the model. Time-evolved distributions of 3O2 concentration were obtained by numerically solving two-dimensional diffusion with-reaction equations both in the capillary and the adjacent tissue. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin-3O2 saturation (SO2) within the vessels, irreversible sensitizer degradation due to photobleaching, and the microscopic distributions of 3O2, sensitizer concentration, and 1O2 dose deposition under various irradiation conditions. The simulations reveal severe axial gradients in 3O2 and in photodynamic dose deposition in response to a wide range of clinically relevant treatment parameters. Thus, unlike former Krogh cylinder-based models, which assume a constant 3O2 concentration at the vessel, this new model identifies conditions in which 3O2 depletion and minimal deposition of reacting 1O2 exist near the end of axial segments of vessels and shows that treatment-limiting 3O2 depletion is induced at fluence rates as low as 10 mW cm(-2). These calculations also demonstrate that intercapillary heterogeneity of photosensitizer contributes significantly to the distribution of photodynamic dose. This more rigorous mathematical model enables comparison with experimentally observable, volume averaged quantities such as SO2 and the loss of sensitizer fluorescence through bleaching that have not been included in previous analyses. Further, it establishes some of the intrinsic limitations of such measurements. Specifically, our simulations demonstrate that tissue measurements of SO2 and of photobleaching are necessarily insensitive to microscopic heterogeneity of photodynamic dose deposition and are sensitive to intercapillary spacing. Because prior knowledge of intercapillary distances in tumors is generally unavailable, these measurements must be interpreted with caution. We anticipate that this model will make useful dosimetry predictions that should inform optimal treatment conditions and improve current clinical protocols. PMID- 17278515 TI - Organ and effective doses in newborns and infants undergoing voiding cystourethrograms (VCUG): a comparison of stylized and tomographic phantoms. AB - The time-sequence videotape-analysis methodology, developed [Sulieman et al., Radiology 178, 653-658 (1991)] for use in tissue dose estimations in adult fluoroscopy examinations and utilized [Bolch et al., Med. Phys. 30, 667-680 (2003)] for analog fluoroscopy in newborn patients, has been extended to the study of digital fluoroscopic examinations of the urinary bladder in newborn and infant female patients. Individual frames of the fluoroscopic and radiographic video were analyzed with respect to unique combinations of field size, field center, projection, tube potential, and tube current (mA), and integral tube current (mAs), respectively. The dosimetry study was conducted on five female patients of ages ranging from four-days to 66 days. For each patient, three different phantoms were utilized: a stylized computational phantom of the reference newborn (3.5 kg), a tomographic computational phantom of the reference newborn (3.5 kg), and (3) a tomographic computational phantom uniformly rescaled to match patient total-body mass. The latter phantom set circumvented the need for mass-dependent rescaling of recorded technique factors (kVp, mA, mAs, etc.), and thus represented the highest degree of patient specificity in the individual organ dose assessment. Effective dose values for the voiding cystourethrogram examination ranged from 0.6 to 3.2 mSv, with a mean and standard deviation of 1.8+/-0.9 mSv. The ovary and colon equivalent doses contributed in total approximately 65%-80% of the effective dose in these fluoroscopy studies. Percent differences in the effective dose assessed using the two tomographic phantoms (one fixed at 3.5 kg with rescaled technique factors rescaled and one physically rescaled to individual patient masses with no adjustment of recorded technique factors) ranged for -49% to +15%. Percent differences in effective dose found using the 3.5 kg stylized phantom and the 3.5 kg tomographic phantom, both with patient-specific rescaling of technique factors, ranged from -10% to +17%. These differences are due in part to a reduced ovary dose in the tomographic phantom for right posterior oblique (RPO) views when compared to those seen in the stylized phantom. PMID- 17278516 TI - Jaws-only IMRT using direct aperture optimization. AB - Using direct aperture optimization, we have developed an inverse planning approach that is capable of producing efficient intensity modulated radiotherapy (IMRT) treatment plans that can be delivered without a multileaf collimator. This "jaws-only" approach to IMRT uses a series of rectangular field shapes to achieve a high degree of intensity modulation from each beam direction. Direct aperture optimization is used to directly optimize the jaw positions and the relative weights assigned to each aperture. Because the constraints imposed by the jaws are incorporated into the optimization, the need for leaf sequencing is eliminated. Results are shown for five patient cases covering three treatment sites: pancreas, breast, and prostate. For these cases, between 15 and 20 jaws only apertures were required per beam direction in order to obtain conformal IMRT treatment plans. Each plan was delivered to a phantom, and absolute and relative dose measurements were recorded. The typical treatment time to deliver these plans was 18 min. The jaws-only approach provides an additional IMRT delivery option for clinics without a multileaf collimator. PMID- 17278517 TI - Performance of a high fill factor, indirect detection prototype flat-panel imager for mammography. AB - Empirical and theoretical investigations of the performance of a small-area, high spatial-resolution, active matrix flat-panel imager, operated under mammographic conditions, is reported. The imager is based on an indirect detection array incorporating a continuous photodiode design, as opposed to the discrete photodiode design employed in conventional flat-panel imagers. Continuous photodiodes offer the prospect of higher fill factors, particularly for arrays with pixel pitches below approximately 100 microm. The array has a pixel-to-pixel pitch of 75 microm and a pixel format of 512 x 512, resulting in an active area of approximately 3.8 x 3.8 cm2. The array was coupled to two commercially available, structured CsI: Tl scintillators of approximately 150 microm thickness: one optimized for high light output (FOS-HL) and the other for high spatial resolution (FOS-HR), resulting in a pair of imager configurations. Measurements of sensitivity, modulation transfer function (MTF), noise power spectra (NPS), and detective quantum efficiency (DQE) were performed with a 26 kVp mammography beam at exposures ranging from approximately 0.5 to approximately 19 mR. MTF results from both CsI:Tl scintillators show that the array demonstrates good spatial resolution, indicating effective isolation between adjacent pixels. The effect of additive noise of the system on DQE was observed to be significantly higher for the FOS-HR scintillator compared to the FOS-HL scintillator due to lower sensitivity of the former. For the FOS-HL scintillator, DQE performance was generally high at high exposures, limited by the x-ray quantum efficiency, Swank factor and the MTF of the scintillators. For both scintillators, the DQE performance degrades at lower exposures due to the relatively large contribution of additive noise. Theoretical calculations based on a cascaded systems model were found to be in general agreement with the empirically determined NPS and DQE values. Finally, such calculations were used to predict potential DQE performance for hypothetical 50 microm pixel pitch imagers, employing similar continuous photodiode design and realistic inputs derived from the empirical measurements. PMID- 17278518 TI - Method to rotate an endovascular device around the axis of a vessel using an external magnetic field. AB - A magnetic guidance methodology to rotate a device around the catheter axis is proposed. The specific medical application is to intracranial aneurysms. An endovascular device, the asymmetric stent, has a low porosity region that is rotated to cover the aneurysm neck so as to reduce the blood flow into and hence obliterate the aneurysm. The magnetic guidance system consists of a magnetic device attached to the asymmetric stent and an external homogeneous magnetic field of 0.1 T. This magnetic field puts a torque on the magnetic moment of the magnetic device, thereby rotating the stent for proper orientation. For the magnetic device with the required magnetic moment of 0.001 A m2, a cylindrical neodymium permanent magnet is proposed due to its favorable material characteristics while a coil electromagnet with iron core appears impractical due to demagnetizing effects. PMID- 17278519 TI - Retrospective monte carlo dose calculations with limited beam weight information. AB - An important unresolved issue in outcomes analysis for lung complications is the effect of poor or completely lacking heterogeneity corrections in previously archived treatment plans. To estimate this effect, we developed a novel method based on Monte Carlo (MC) dose calculations which can be applied retrospectively to RTOG/AAPM-style archived treatment plans (ATP). We applied this method to 218 archived nonsmall cell lung cancer lung treatment plans that were originally calculated either without heterogeneity corrections or with primitive corrections. To retrospectively specify beam weights and wedges, beams were broken into Monte Carlo-generated beamlets, simulated using the VMC++ code, and mathematical optimization was used to match the archived water-based dose distributions. The derived beam weights (and any wedge effects) were then applied to Monte Carlo beamlets regenerated based on the patient computed tomography densities. Validation of the process was performed against five comparable lung treatment plans generated using a commercial convolution/superposition implementation. For the application here (normal lung, esophagus, and planning target volume dose distributions), the agreement was very good. Resulting MC and convolution/superposition values were similar when dose distributions without heterogeneity corrections or dose distributions with corrections were compared. When applied to the archived plans (218), the average absolute percent difference between water-based MC and water-based ATPs, for doses above 2.5% of the maximum dose was 1.8+/-0.6%. The average absolute percent difference between heterogeneity-corrected MC and water-based ATPs increased to 3.1+/-0.9%. The average absolute percent difference between the MC heterogeneity-corrected and the ATP heterogeneity-corrected dose distributions was 3.8+/-1.6% (available in 132/218 archives). The entire dose-volume-histograms for lung, tumor, and esophagus from the different calculation methods, as well as specific dose metrics, were compared. The average difference in maximum lung dose between water based ATPs and heterogeneity-corrected MC dose distributions was -1.0+/-2.1 Gy. Potential errors in relying on primitive heterogeneity corrections are most evident from a comparison of maximum lung doses, for which the average MC heterogeneity-corrected values were 5.3+/-2.8 Gy less than the ATP heterogeneity corrected values. We have demonstrated that recalculation of archived dose distributions, without explicit information about beam weights or wedges, is feasible using beamlet-based optimization methods. The method provides heterogeneity-corrected dose data consistent with convolution-superposition calculations and is one feasible approach for improving dosimetric data for outcomes analyses. PMID- 17278520 TI - Effect of respiratory motion on the delivery of breast radiotherapy using SMLC intensity modulation. AB - This study evaluates the effects of respiratory motion on breast radiotherapy delivered using segmented multileaf collimator (SMLC) intensity modulation. An anthropomorphic breast phantom was constructed of polystyrene plates between which radiographic films were inserted. The phantom was mounted on a moving platform to simulate one-dimensional sinusoidal oscillation with variable amplitude and frequency. The motion effect on two breast IMRT techniques, a beamlet-based plan created using the Corvus treatment planning system and an aperture-based plan, was evaluated via film comparison. Motion-induced differences in the treatment region are generally within +5%, with the exception of the posterior field edge and the apex of the breast in the Corvus IMRT plan. Considering the experimental uncertainty arising from the setup and film dosimetry, this result indicates that respiratory motion-induced dose variations are generally relatively insignificant. It appears that the anterior hot spots observed in the Corvus IMRT plan result from the high intensity fluence delivered to the "virtual bolus" area which must be created during the planning process in order to provide "flash" for the respiratory motion. The potential magnitude of such effects resulting from the interplay between fluence modulation and patient motion are unique to the individual planning system and planning technique, as well as the delivery equipment and technique. Such effects should be carefully investigated prior to the implementation of IMRT for breast radiotherapy. PMID- 17278521 TI - Dosimetric evaluation of daily rigid and nonrigid geometric correction strategies during on-line image-guided radiation therapy (IGRT) of prostate cancer. AB - The purpose of this study is to evaluate a geometric image guidance strategy that simultaneously correct for various inter-fractional rigid and nonrigid geometric uncertainties in an on-line environment, using field shape corrections (called the "MU-MLC" technique). The effectiveness of this strategy was compared with two other simpler on-line image guidance strategies that are more commonly used in the clinic. To this end, five prostate cancer patients, with at least 15 treatment CT studies each, were analyzed. The prescription dose was set to the maximum dose that did not violate the rectum and bladder dose-volume constraints, and hence, was unique to each patient. Deformable image registration and dose tracking was performed on each CT image to obtain the cumulative treatment dose distributions. From this, maximum, minimum, and mean dose, as well as generalized equivalent uniform dose (gEUD) were calculated for each image guidance strategy. As expected, some dosimetric differences in the clinical target volume (CTV) were observed between the three image guidance strategies investigated. For example, up to +/-2% discrepancy in prostate minimum dose were observed among the techniques. Of them, only the "MU -MLC" technique did not reduce the prostate minimum dose for all patients (i.e., > or = 100%). However, the differences were clinically not significant to indicate the preference of one strategy over another, when using a uniform 5 mm margin size. For the organ-at-risks (OARs), the large rectum sparing effect (< or =5.7 Gy, gEUD) and bladder overdosing effect (< or = 16 Gy, gEUD) were observed. This was likely due to the use of bladder contrast during CT simulation studies which was not done during the treatment CT studies. Therefore, ultimately, strategies to maintain relatively constant rectum and bladder volumes, throughout the treatment course, are required to minimize this effect. In conclusion, the results here suggest that simple translational corrections based on three-dimensional (3D) images is adequate to maintain target coverage, for margin sizes at least as large as 5 mm. In addition, due to large fluctuations in OAR volumes, innovative image guidance strategies are needed to minimize dose and maintain consistent sparing during the whole course of radiation therapy. PMID- 17278522 TI - Comment on: "Basic investigations on the performance of a normoxic polymer gel with tetrakis-hydroxy-methyl-phosphonium chloride as an oxygen scavenger: reproducibility, accuracy, stability, and dose rate dependence" [Med. Phys. 33, 2506-2518 (2006)]. PMID- 17278523 TI - The need for a dose calibration protocol for brachytherapy sources. PMID- 17278524 TI - Dynamics of target selection in multiple object tracking (MOT). AB - In four experiments we address the question whether several visual objects can be selected voluntarily (exogenously) and then tracked in a Multiple Object Tracking paradigm and, if so, whether the selection involves a different process. Experiment 1 showed that items can indeed be selected based on their labels. Experiment 2 showed that to select the complement set to a set that is automatically (exogenously) selected--e.g. to select all objects not flashed- observers require additional time and that given 1080 ms they were able to select and track them as well as those selected automatically. Experiment 3 showed that the additional time needed in the previous experiment cannot be attributed solely to time required to disengage attention from the initially automatic selections. Experiment 4 showed that the added time provides a monotonically greater benefit when there are more targets, suggesting a serial process. These results are discussed in relation to the Visual Index (FINST) theory which assumes that visual indexes are captured by a data-driven process. It is suggested that voluntarily allocated attention can be used to facilitate the automatic attention capture by objects of interest. PMID- 17278526 TI - Searching for asymmetries in the detection of gaze contact versus averted gaze under different head views: a behavioural study. AB - Eye contact is a crucial social cue constituting a frequent preliminary to interaction. Thus, the perception of others' gaze may be associated with specific processes beginning with asymmetries in the detection of direct versus averted gaze. We tested this hypothesis in two behavioural experiments using realistic eye stimuli in a visual search task. We manipulated the head orientation (frontal or deviated) and the visual field (right or left) in which the target appeared at display onset. We found that direct gaze targets presented among averted gaze distractors were detected faster and better than averted gaze targets among direct gaze distractors, but only when the head was deviated. Moreover, direct gaze targets were detected very quickly and efficiently regardless of head orientation and visual field, whereas the detection of averted gaze was strongly modulated by these factors. These results suggest that gaze contact has precedence over contextual information such as head orientation and visual field. PMID- 17278525 TI - On the origin of vertical line bisection errors. AB - Four experiments examined the biases of individual subjects when attempting to bisect vertical lines, and tested various hypotheses concerning the origin of vertical bisection errors (VBEs). In each experiment, individual differences on the vertical line bisection task were compared to individual differences on another task to evaluate whether the tasks were systematically related. In the first experiment, VBEs were found not to correlate with horizontal line bisection errors (HBEs). In the second experiment, VBEs were found not to correlate with the size of the horizontal-vertical illusion (HVI). In the third experiment, VBEs were found not to correlate with differences in perceived length of vertical lines presented in the upper and lower visual fields that were displaced horizontally. In the fourth experiment, VBEs were found to correlate with bisection errors of an open vertical interval. The results of the first three studies are counter to various hypotheses of the origins of vertical bisection errors. The last experiment suggests that lines, per se, are unnecessary for VBEs. Rather, it is important that the upper and lower segments of the stimulus that are judged to be equal on vertical bisection tasks are co-extensive. PMID- 17278527 TI - Chromatic collinear facilitation, further evidence for chromatic form perception. AB - Collinear facilitation of contrast detection of achromatic stimuli has been studied over the past decade by different groups. We measured collinear facilitation of chromatic contrast detection under equal-luminance (photometric quantity) and under isoluminance (minimum motion technique) conditions, as two different controls. The facilitation was tested for chromatic contrast detection of a foveal Gabor signal flanked by two high chromatic-contrast Gabor signals. The results indicated a significant facilitation in the presence of spatial adjacent collinear chromatic contrast signals, when the flankers were located at a short distance, across all observers for three chromatic channels. The facilitation was compared to a non-collinear flanker configuration. The results indicated no facilitation effect at the opposing phase configuration, at a short flanker distance, whereas a small facilitation was observed with a configuration at a longer flanker distance. The findings suggest that the performance and specificity of chromatic collinear facilitation is not impaired with regard to achromatic mechanisms. PMID- 17278528 TI - Influences of attention on auditory aftereffects following purely visual adaptation. AB - Recently, Kitagawa and Ichihara (2002) demonstrated that visual adaptation to an expanding or contracting disk produces a cross-modal visually-induced auditory loudness aftereffect (VALAE), which they attributed to cross-correlations of motion in three-dimensional space. Our experiments extend their results by providing evidence that attending selectively to one of two competing visual stimuli of the same saliency produces a cross-modal VALAE that favors the attended stimulus. These cross-modal attentional effects suggest the existence of integrative spatial mechanisms between vision and audition that are affected by attention. PMID- 17278529 TI - Illusory boundary interpolation from local association field. AB - We previously showed that interpolation between vertically misaligned luminance edges of same polarity of contrast is preferred to that between co-linear edges of opposite polarity of contrast, although it results in illusory tilt (Roncato and Casco, 2003). We here analyze the spatial conditions that produce this illusory binding of vertically misaligned edges of light and dark tiles, alternated in a row, and in counterphase with those in the rows above and below. We find that, independently of scale and number of tiles in a row, the illusion is perceived when the vertical misalignment of more than three tiles is smaller than or equal to 9' and the horizontal separation between co-linear edges is smaller than or equal to 13'. These short distances suggest that the underlying mechanism is local. Both our phenomenological and psychophysical results support the notion of a local short-range association field, selective to contrast polarity, which produces a binding solution different from that of a phase independent long-range mechanism. We suggest that the occurrence of the illusion at local-level is a result of the activation, within a local short-range association field, of units with orientation different from that stimulated by the physical edges. These units are not inhibited when they are close, iso oriented and co-linear, and the misaligned edges from which they propagate have the same contrast polarity. We found that horizontal and vertical spatial limits for the interpolation covary but not such that their ratio is fixed, indicating that the two edges can be connected by projections having a relatively wide range of orientations. PMID- 17278530 TI - Increased levels of transforming growth factor-betal and -beta2 in the aqueous humor of patients with neovascular glaucoma. AB - BACKGROUND AND OBJECTIVE: To measure the concentrations of transforming growth factor-betal and beta2 (TGF-beta1 and TGF-beta2) in the aqueous humor of patients with neovascular glaucoma (NVG). PATIENTS AND METHODS: Patients were divided into four groups: NVG secondary to central retinal vein occlusion (group 1), NVG secondary to proliferative diabetic retinopathy (group 2), central retinal vein occlusion without rubeosis (group 3), and senile cataract (group 4). The total TGF-beta 1 and TGF-beta2 concentrations in the aqueous humor of the four groups were measured by enzyme linked immunosorbent assay. RESULTS: The mean concentrations of total TGF-betal were 600.7 +/-436.7 microg/mL in group 1, 802.0 +/-359.5 pg/mL in group 2, and undetectable in groups 3 and group 4 (P < .05). The mean concentrations of total TGF-beta2 were 6,307.9+/- 2,206.2 microg/mL in group 1, 5,908.0+/-2,033.2 microg/mL in group 2, 899.7+/- 425.6 microg/mL in group 3, and 385.7 +/-89.9 microg/mL in group 4. The total TGF-betal and TGF beta2 concentrations in groups 1 and 2 were significantly higher than those in groups 3 and 4, whereas the total TGF-beta2 concentration in group 3 was significantly higher than that in group 4 (P < .05). There was no significant difference in the TGF-betal or TGF-beta2 concentrations between groups 1 and 2 (P> .05). CONCLUSIONS: The abnormally high concentrations of TGF-betal and TGF beta2 in the aqueous humor of patients with NVG may explain some aspects of the pathogenesis of NVG and the high failure rate of filtering operations in NVG. PMID- 17278531 TI - Surgical management of retinal detachment in highly myopic eyes with macular hole. AB - BACKGROUND AND OBJECTIVES: To evaluate the visual and anatomical outcomes of surgery for retinal detachment due to macular hole in highly myopic eyes with pronounced posterior staphyloma. PATIENTS AND METHODS: Data for all patients with high myopia who underwent surgery for retinal detachment resulting from macular hole from 1993 to 2002 in one hospital were evaluated. Patient characteristics, best-corrected visual acuity preoperatively and at last examination, surgical technique, anatomical success, and follow-up period were extracted and analyzed statistically. RESULTS: Twenty-six of the 27 patients (28 eyes) were female (96%) with a mean age of 59.8 years; mean follow-up was 17.3 months. Mean axial length was 29.1+/-2.74 mm; mean myopia was -16.4 +/- 3.1 diopters. Marked posterior staphyloma was detected in 71%. Seven eyes had undergone failed scleral buckling as the primary procedure; intravitreal SF6 injection was the primary procedure in 12 eyes. Twenty-three eyes underwent deep vitrectomy with use of high viscosity silicone oil. Overall anatomical success was achieved in 92.9% (26 of 28 eyes); 78.6% had visual improvement. CONCLUSIONS: Vitreous surgery combined with other necessary adjunct procedures such as membrane peeling and use of retinal tamponade, as a primary or a secondary procedure, seems to be successful in achieving retinal reattachment in eyes with macular hole and posterior staphyloma. PMID- 17278532 TI - Cataract surgery takes longer in functionally monocular patients. AB - BACKGROUND AND OBJECTIVES: To determine differences in the amount of work involved in caring for functionally monocular patients who undergo cataract surgery compared with binocularly sighted patients. PATIENTS AND METHODS: This was a retrospective study that included 100 consecutive functionally monocular patients and 100 binocularly sighted control patients matched by age (+/-5 years) and date of surgery ( +/-1 year). Office records were reviewed to determine several measures of office and operating room work effort. RESULTS: There was no difference between groups in preoperative telephone calls (P = .136), postoperative telephone calls (P = .580), preoperative office visits (P = .875), postoperative office visits (P = .601), or the number of times surgery was scheduled (P = 1.00). Monocular patients required more time for surgery (37.4 minutes) than binocular patients (32.4 minutes) (P= .010). CONCLUSIONS: It takes longer to perform cataract surgery on functionally monocular patients than on binocularly sighted patients. PMID- 17278533 TI - Imaging of iris lesions with high-speed optical coherence tomography. AB - BACKGROUND AND OBJECTIVES: To image and measure iris tumors with optical coherence tomography (OCT). PATIENTS AND METHODS: High-speed (2,000-4,000 axial scan/sec and 4-16 frames/sec) 1.3-micron wavelength anterior segment OCT prototypes were used to image 6 eyes of 6 patients with a variety of iris lesions, including focal iris nevus, diffuse iris nevus, amelanotic iris nevus, iris melanocytosis, and iris melanoma. OCT images were compared with slit-lamp photography and ultrasound biomicroscopy. RESULTS: OCT at 1.3-micron wavelength could penetrate the full thickness of the iris lesions and allow three dimensional measurement of lesion size. Internal reflectivity is correlated with pigmentation. OCT is a convenient non-contact method that provides imaging of the clinically important angle structures (scleral spur and angle recess). CONCLUSIONS: OCT is a new imaging modality that complements slit-lamp photography and ultrasound biomicroscopy for serial evaluation of iris PMID- 17278535 TI - Estimation of intraocular pressure in rabbits with commonly used tonometers. AB - BACKGROUND AND OBJECTIVES: To validate accuracy and reproducibility of the Perkins tonometer, pneumatonometer, and Tono-Pen XL (Medtronic Solan, Jacksonville, FL) in estimating intraocular pressure (IOP) in rabbits. MATERIALS AND METHODS: IOP was increased from 5 to 50 mm Hg in 5-mm increments. Measurements were compared to readings of two digital manometers simultaneously measuring real IOP in the anterior chamber and vitreous cavity. Interobserver accuracy was evaluated using 4 eyes with the Perkins tonometer. RESULTS: The Perkins tonometer and Tono-Pen XL underestimated IOP and were more accurate at pressures less than 30 mm Hg. No statistically significant difference was found between real IOP and Tono-Pen XL readings. The pneumatonometer overestimated pressures in the low ranges but was accurate at pressures greater than 40 mm Hg. The Tono-Pen XL had more variability than the Perkins tonometer and pneumatonometer at high IOP. CONCLUSIONS: None of the tonometers are accurate or reproducible in estimating IOP in rabbits over the tested range. Pneumatonometry, although not very accurate, has the advantage of having acceptable variability. PMID- 17278534 TI - A method for three-dimensional imaging of the retina in human eyes. AB - BACKGROUND AND OBJECTIVES: An optical system for three-dimensional imaging of the retinal tissue in human eyes is described. PATIENTS AND METHODS: A laser beam was projected at an oblique angle on the retina and scanned to acquire 40 optical section images in a 1.0 x 1.5 mm retinal area. Because the incident laser beam was not coaxial with the viewing system, structures at various retinal depths appeared laterally displaced according to their depth location on the optical section image. The optical section images were segmented to construct a series of en face retinal images, parallel to the retinal surface and displaced in depth. Imaging was performed in three control subjects. RESULTS: A series of 8 depth displaced en face images of retinal layers was reconstructed in each eye, which allowed enhanced visualization of the retinal structures and vasculatures. En face depth-displaced retinal images provided improved contrast compared with fundus images and delineated the foveal depression and the surrounding retinal vasculatures. CONCLUSIONS: An optical system for three-dimensional retinal imaging was developed that has potential as a tool for evaluation of retinal pathologies associated with chorioretinal diseases. PMID- 17278536 TI - Comparison between a fundus camera and scanning laser ophthalmoscope in acquiring fluorescence emission in vitro. AB - BACKGROUND AND OBJECTIVES: To compare the fluorescence measurements acquired from a fundus camera with those from a scanning laser ophthalmoscope (SLO) camera. MATERIALS AND METHODS: The fundus camera and the SLO camera were used to capture images of 29 cuvettes each containing serially diluted sodium fluorescein dye in normal saline. The intensity levels of the resulting images were plotted as a function of concentration to compare the two cameras. Ten samples of serially diluted indocyanine green (ICG) dye in bovine serum were also measured. RESULTS: Both cameras revealed that fluorescence intensity varied as a function of the logarithmic concentration of the dye, independent of the actual dye used, with expected decrease in fluorescence at very high concentrations of dye due to quenching of fluorescence. There were very small variations on repeated trials with the fundus camera, whereas the SLO camera exhibited marked variability, particularly at higher concentrations of dye. Measurements acquired with the SLO camera varied as a function of time, which did not occur with the fundus camera. The image averaging software on the SLO camera caused shifts in the grayscale values measured that depended on the initial amount of fluorescence measured in the raw samples. CONCLUSIONS: Although these differences may cause modest qualitative differences in imaging the ocular fundus, the variation in data obtained from the SLO camera would seem problematic if quantification of the amounts of fluorescence is required. PMID- 17278537 TI - Late onset of acute angle-closure glaucoma following neodymium:YAG laser posterior capsulotomy. AB - Acute angle-closure glaucoma due to vitreous prolapse immediately following neodymium:YAG (Nd:YAG) laser posterior capsulotomy in eyes with posterior chamber intraocular lens implants is rare. Previously described cases were associated with advanced age, excessive amounts of laser energy, and a large-diameter capsular opening. The authors describe a case of acute angle-closure glaucoma occurring 21 days after Nd:YAG laser posterior capsulotomy in a young patient with a small-diameter capsule opening and a small amount of laser energy to stress the importance of close extended follow-up even in eyes with a theoretical low risk for this complication PMID- 17278538 TI - Full-thickness eccentric macular hole following vitrectomy with internal limiting membrane peeling. AB - A 65-year-old man presented after macular hole surgery with trypan blue-assisted internal limiting membrane peeling in his left eye. Although the patient had no visual complaints in the left eye, on clinical examination an eccentric full thickness macular hole was noted just inside the superior vascular arcade and documented by optical coherence tomography. The patient was observed and continued to remain asymptomatic. PMID- 17278539 TI - Surgical management of inner lamellar macular hole. AB - The purpose of this study was to determine whether pars plana vitrectomy membrane peeling and fluid-air exchange could improve optical coherence tomography and visual acuity outcomes in a patient with an inner lamellar macular hole when the patient remains in the face-down position for 3 days after surgery. Three weeks postoperatively, optical coherence tomography revealed a normal macular contour. Two months postoperatively, best-corrected visual acuity improved from 20/60 to 20/30. Surgery may be a useful option to study further in patients with symptomatic inner lamellar macular holes. PMID- 17278541 TI - Valsalva retinopathy associated with vigorous dancing in a discotheque. AB - Valsalva retinopathy develops in response to a Valsalva maneuver. Decreased visual acuity may be caused by preretinal hemorrhage, which is related to the fovea, or by vitreous hemorrhage. The hemorrhage usually clears spontaneously. A case of Valsalva maculopathy in a young, healthy boy caused by physical exertion while dancing at a club is described. Reduced visual acuity and premacular hemorrhage spontaneously resolved during the 5-month postoperative period. PMID- 17278540 TI - Large submacular hemorrhage following PDT with verteporfin in patients with occult CNVM secondary to age-related macular degeneration. AB - A review of the charts for all patients who developed large submacular hemorrhages following photodynamic therapy for choroidal neovascular membranes secondary to age-related macular degeneration yielded three patients who met the criteria for a large submacular hemorrhage. All three patients were treated for exudative age-related macular degeneration and were taking warfarin for chronic anticoagulation. Before photodynamic therapy, the international normalized ratio ranged from 1.2 to 1.6. All three patients had received at least one previous verteporfin treatment in the study eye. All three hemorrhages were not noted immediately after photodynamic therapy and were documented within 1 to 2 weeks following the procedure. Patients with age-related macular degeneration who are receiving warfarin therapy and undergoing repeat verteporfin treatments appear to be at risk for submacular hemorrhages. PMID- 17278542 TI - Ab externo technique for accurate haptic placement of transscleral sutured posterior chamber intraocular lenses. AB - A modified technique is presented for transscleral suture fixation of posterior chamber intraocular lenses for aphakic correction in cases with inadequate capsular support. An ab externo approach for suture externalization is described that minimizes intraocular manipulation and facilitates accurate placement of haptics in the ciliary sulcus, thereby reducing the risk of lens tilt and decentration. This technique eliminates intraocular suture knots and reduces the amount of time the globe is open during surgery by creating two intraocular suture loops in preparation for posterior chamber intraocular lens placement before creating a limbal incision. PMID- 17278543 TI - A new small-incision technique for injector implantation of transsclerally sutured foldable lenses. AB - A new, minimally invasive technique for clear cornea implantation of one-piece acrylic posterior chamber lenses for transscleral suture fixation in aphakic eyes without capsular support is described. Based on the techniques of modern small incision cataract surgery, implantation was performed through a self-sealing, 2.75-mm temporal clear cornea incision using the injector technique. This was possible by modifying the insertion of the lens into the cartridge and introducing a new suturing technique of the lens. Suturing of the leading haptic end was performed while the lens was still securely stored inside the cartridge. The trailing haptic was tied after implantation. By using a self-sealing tunnel incision and injector technique, significant fluid egress and consecutive transient hypotony may be minimized throughout the procedure and early visual rehabilitation achieved. PMID- 17278545 TI - Total care system for maintaining a comfortable prone position after vitreoretinal surgery. AB - A care system to maintain a comfortable prone position after vitreoretinal surgery was developed. Four positions and face-down gear including a TV-watching table were prepared in patients' rooms. Patients could take one position and then change to another position actively as desired. Thirty-nine patients used this system for 4 days after vitreoretinal surgery with intravitreal gas injection. Patients rated the system on a questionnaire. Patients who used the TV-watching table expressed more satisfaction than the patients who did not use it. Also, patients' active selection of various prone postures was important physically and mentally. PMID- 17278546 TI - Use of the Honan balloon as a compression device for intravitreal triamcinolone acetonide injection. AB - Obtaining a lower intraocular pressure (IOP) before an intravitreal injection is important to avoid the danger of an immediate increase in IOP. This article describes the use of the Honan balloon to reduce the IOP before an intravitreal triamcinolone acetonide injection instead of the other procedures described in the literature, which may increase the risk of complications. The results of the technique in 19 patients with retinal vein occlusion are reported. Honan balloon was applied at 30 mm Hg for 10 minutes and the injection was then performed no more than 5 minutes after the removal of the Honan balloon. In no more than 10 minutes, this procedure resulted in a significant reduction in IOP. No complications such as central retinal artery occlusion were observed after the injection. PMID- 17278548 TI - Disaster recovery. PMID- 17278544 TI - Successful removal of a large conjunctival cyst using colored 2.3% sodium hyaluronate. AB - A 39-year-old woman was referred for the management of a large conjunctival cyst in her right eye. A mixture of trypan blue and 2.3% sodium hyaluronate was injected into the cyst using a 27-gauge needle to achieve a complete removal of the cyst. This new technique provided excellent visualization to achieve an easy and complete resection of the large conjunctival cyst. Colored 2.3% sodium hyaluronate is effective in delineating the capsule and preserving its integrity during the removal of a large conjunctival cyst. Such a technique may also have a role in facilitating visualization and excision of other cystic lesions from the ocular surface. PMID- 17278547 TI - What's happening in health informatics? PMID- 17278549 TI - Vendor consolidation: still riding the wave. Plenty of buyers and sellers in 2006 as vendors tried to get footholds in growing niches. PMID- 17278550 TI - Practices go beyond basics with EDI. Clinics are starting to use electronic data interchange for more than just claims processing. PMID- 17278551 TI - Software tackles a persistent challenge. PMID- 17278552 TI - EMRs are still full of surprises. PMID- 17278553 TI - Readers perspectives. "The majority of physicians will not voluntarily adopt speech recognition and self-editing transcribing technology". PMID- 17278554 TI - Coevolving memetic algorithms: a review and progress report. AB - Coevolving memetic algorithms are a family of metaheuristic search algorithms in which a rule-based representation of local search (LS) is coadapted alongside candidate solutions within a hybrid evolutionary system. Simple versions of these systems have been shown to outperform other nonadaptive memetic and evolutionary algorithms on a range of problems. This paper presents a rationale for such systems and places them in the context of other recent work on adaptive memetic algorithms. It then proposes a general structure within which a population of LS algorithms can be evolved in tandem with the solutions to which they are applied. Previous research started with a simple self-adaptive system before moving on to more complex models. Results showed that the algorithm was able to discover and exploit certain forms of structure and regularities within the problems. This "metalearning" of problem features provided a means of creating highly scalable algorithms. This work is briefly reviewed to highlight some of the important findings and behaviors exhibited. Based on this analysis, new results are then presented from systems with more flexible representations, which, again, show significant improvements. Finally, the current state of, and future directions for, research in this area is discussed. PMID- 17278555 TI - An effective PSO-based memetic algorithm for flow shop scheduling. AB - This paper proposes an effective particle swarm optimization (PSO)-based memetic algorithm (MA) for the permutation flow shop scheduling problem (PFSSP) with the objective to minimize the maximum completion time, which is a typical non deterministic polynomial-time (NP) hard combinatorial optimization problem. In the proposed PSO-based MA (PSOMA), both PSO-based searching operators and some special local searching operators are designed to balance the exploration and exploitation abilities. In particular, the PSOMA applies the evolutionary searching mechanism of PSO, which is characterized by individual improvement, population cooperation, and competition to effectively perform exploration. On the other hand, the PSOMA utilizes several adaptive local searches to perform exploitation. First, to make PSO suitable for solving PFSSP, a ranked-order value rule based on random key representation is presented to convert the continuous position values of particles to job permutations. Second, to generate an initial swarm with certain quality and diversity, the famous Nawaz-Enscore-Ham (NEH) heuristic is incorporated into the initialization of population. Third, to balance the exploration and exploitation abilities, after the standard PSO-based searching operation, a new local search technique named NEH_1 insertion is probabilistically applied to some good particles selected by using a roulette wheel mechanism with a specified probability. Fourth, to enrich the searching behaviors and to avoid premature convergence, a simulated annealing (SA)-based local search with multiple different neighborhoods is designed and incorporated into the PSOMA. Meanwhile, an effective adaptive meta-Lamarckian learning strategy is employed to decide which neighborhood to be used in SA-based local search. Finally, to further enhance the exploitation ability, a pairwise-based local search is applied after the SA-based search. Simulation results based on benchmarks demonstrate the effectiveness of the PSOMA. Additionally, the effects of some parameters on optimization performances are also discussed. PMID- 17278556 TI - A fast adaptive memetic algorithm for online and offline control design of PMSM drives. AB - A fast adaptive memetic algorithm (FAMA) is proposed which is used to design the optimal control system for a permanent-magnet synchronous motor. The FAMA is a memetic algorithm with a dynamic parameter setting and two local searchers adaptively launched, either one by one or simultaneously, according to the necessities of the evolution. The FAMA has been tested for both offline and online optimization. The former is based on a simulation of the whole system- control system and plant--using a model obtained through identification tests. The online optimization is model free because each fitness evaluation consists of an experimental test on the real motor drive. The proposed algorithm has been compared with other optimization approaches, and a matching analysis has been carried out offline and online. Excellent results are obtained in terms of optimality, convergence, and algorithmic efficiency. Moreover, the FAMA has given very robust results in the presence of noise in the experimental system. PMID- 17278557 TI - A multiobjective memetic algorithm based on particle swarm optimization. AB - In this paper, a new memetic algorithm (MA) for multiobjective (MO) optimization is proposed, which combines the global search ability of particle swarm optimization with a synchronous local search heuristic for directed local fine tuning. A new particle updating strategy is proposed based upon the concept of fuzzy global-best to deal with the problem of premature convergence and diversity maintenance within the swarm. The proposed features are examined to show their individual and combined effects in MO optimization. The comparative study shows the effectiveness of the proposed MA, which produces solution sets that are highly competitive in terms of convergence, diversity, and distribution. PMID- 17278558 TI - Evolutionary algorithms refining a heuristic: a hybrid method for shared-path protections in WDM networks under SRLG constraints. AB - An evolutionary algorithm (EA) can be used to tune the control parameters of a construction heuristic to an optimization problem and generate a nearly optimal solution. This approach is in the spirit of indirect encoding EAs. Its performance relies on both the heuristic and the EA. This paper proposes a three phase parameterized construction heuristic for the shared-path protection problem in wavelength division multiplexing networks with shared-risk link group constraints and applies an EA for optimizing the control parameters of the proposed heuristics. The experimental results show that the proposed approach is effective on all the tested network instances. It was also demonstrated that an EA with guided mutation performs better than a conventional genetic algorithm for tuning the control parameters, which indicates that a combination of global statistical information extracted from the previous search and location information of the best solutions found so far could improve the performance of an algorithm. PMID- 17278559 TI - A memetic algorithm for VLSI floorplanning. AB - Floorplanning is an important problem in very large scale integrated-circuit (VLSI) design automation as it determines the performance, size, yield, and reliability of VLSI chips. From the computational point of view, VLSI floorplanning is an NP-hard problem. In this paper, a memetic algorithm (MA) for a nonslicing and hard-module VLSI floorplanning problem is presented. This MA is a hybrid genetic algorithm that uses an effective genetic search method to explore the search space and an efficient local search method to exploit information in the search region. The exploration and exploitation are balanced by a novel bias search strategy. The MA has been implemented and tested on popular benchmark problems. Experimental results show that the MA can quickly produce optimal or nearly optimal solutions for all the tested benchmark problems. PMID- 17278560 TI - Wrapper-filter feature selection algorithm using a memetic framework. AB - This correspondence presents a novel hybrid wrapper and filter feature selection algorithm for a classification problem using a memetic framework. It incorporates a filter ranking method in the traditional genetic algorithm to improve classification performance and accelerate the search in identifying the core feature subsets. Particularly, the method adds or deletes a feature from a candidate feature subset based on the univariate feature ranking information. This empirical study on commonly used data sets from the University of California, Irvine repository and microarray data sets shows that the proposed method outperforms existing methods in terms of classification accuracy, number of selected features, and computational efficiency. Furthermore, we investigate several major issues of memetic algorithm (MA) to identify a good balance between local search and genetic search so as to maximize search quality and efficiency in the hybrid filter and wrapper MA. PMID- 17278561 TI - On the hybridization of memetic algorithms with branch-and-bound techniques. AB - Branch-and-bound (BnB) and memetic algorithms represent two very different approaches for tackling combinatorial optimization problems. However, these approaches are compatible. In this correspondence, a hybrid model that combines these two techniques is considered. To be precise, it is based on the interleaved execution of both approaches. Since the requirements of time and memory in BnB techniques are generally conflicting, a truncated exact search, namely, beam search, has opted to be carried out. Therefore, the resulting hybrid algorithm has a heuristic nature. The multidimensional 0-1 knapsack problem and the shortest common supersequence problem have been chosen as benchmarks. As will be shown, the hybrid algorithm can produce better results in both problems at the same computational cost, especially for large problem instances. PMID- 17278562 TI - A memetic algorithm for multiple-drug cancer chemotherapy schedule optimization. AB - This correspondence introduces a multidrug cancer chemotherapy model to simulate the possible response of the tumor cells under drug administration. We formulate the model as an optimal control problem. The algorithm in this correspondence optimizes the multidrug cancer chemotherapy schedule. The objective is to minimize the tumor size under a set of constraints. We combine the adaptive elitist genetic algorithm with a local search algorithm called iterative dynamic programming (IDP) to form a new memetic algorithm (MA-IDP) for solving the problem. MA-IDP has been shown to be very efficient in solving the multidrug scheduling optimization problem. PMID- 17278563 TI - Implementation of an effective hybrid GA for large-scale traveling salesman problems. AB - This correspondence describes a hybrid genetic algorithm (GA) to find high quality solutions for the traveling salesman problem (TSP). The proposed method is based on a parallel implementation of a multipopulation steady-state GA involving local search heuristics. It uses a variant of the maximal preservative crossover and the double-bridge move mutation. An effective implementation of the Lin-Kernighan heuristic (LK) is incorporated into the method to compensate for the GA's lack of local search ability. The method is validated by comparing it with the LK-Helsgaun method (LKH), which is one of the most effective methods for the TSP. Experimental results with benchmarks having up to 316228 cities show that the proposed method works more effectively and efficiently than LKH when solving large-scale problems. Finally, the method is used together with the implementation of the iterated LK to find a new best tour (as of June 2, 2003) for a 1904711-city TSP challenge. PMID- 17278564 TI - Estimation of the dynamic spinal forces using a recurrent fuzzy neural network. AB - Estimation of the dynamic spinal forces from kinematics data is very complicated because it involves the handling of the relationship between kinematic variables and electromyography (EMG) signals, as well as the relationship between EMG signals and the forces. A recurrent fuzzy neural network (RFNN) model is proposed to establish the kinematics-EMG-force relationship and model the dynamics of muscular activities. The EMG signals are used as an intermediate output and are fed back to the input layer. Since EMG is a direct reflection of muscular activities, the feedback of this model has a physical meaning. It expresses the dynamics of muscular activities in a straightforward way and takes advantage from the recurrent property. The trained model can then have the forces predicted directly from kinematic variables while bypassing the costly procedure of measuring EMG signals and avoiding the use of a biomechanics model. A learning algorithm is derived for the RFNN model. PMID- 17278565 TI - Robust fault-tolerant control for a biped robot using a recurrent cerebellar model articulation controller. AB - A design technique of a recurrent cerebellar model articulation controller (RCMAC)-based fault-tolerant control (FTC) system is investigated to rectify the nonlinear faults of a biped robot. The proposed RCMAC-based FTC (RCFTC) scheme contains two components: 1) an online fault estimation module based on an RCMAC is used to provide approximation information for any nonnominal behavior due to the system failure and modeling error of the biped robot; and 2) a controller module consisting of a computed torque controller and a robust FTC is utilized to achieve FTC. In the controller module, the computed torque controller reveals a basic stabilizing controller to stabilize the system, and the robust FTC is utilized to compensate for the effects of the system failure so as to achieve fault accommodation. The adaptive laws of the RCFTC system are rigorously established based on the Lyapunov function, so that the stability of the system can be guaranteed. Finally, two simulation cases of a biped robot are presented to illustrate the effectiveness of the proposed design method. Simulation results show that the RCFTC system can effectively recover the control performance for the system in the presence of the nonlinear faults and modeling uncertainties. PMID- 17278566 TI - Kernel CMAC with improved capability. AB - The cerebellar model articulation controller (CMAC) has some attractive features, namely fast learning capability and the possibility of efficient digital hardware implementation. Although CMAC was proposed many years ago, several open questions have been left even for today. The most important ones are about its modeling and generalization capabilities. The limits of its modeling capability were addressed in the literature, and recently, certain questions of its generalization property were also investigated. This paper deals with both the modeling and the generalization properties of CMAC. First, a new interpolation model is introduced. Then, a detailed analysis of the generalization error is given, and an analytical expression of this error for some special cases is presented. It is shown that this generalization error can be rather significant, and a simple regularized training algorithm to reduce this error is proposed. The results related to the modeling capability show that there are differences between the one-dimensional (1-D) and the multidimensional versions of CMAC. This paper discusses the reasons of this difference and suggests a new kernel-based interpretation of CMAC. The kernel interpretation gives a unified framework. Applying this approach, both the 1-D and the multidimensional CMACs can be constructed with similar modeling capability. Finally, this paper shows that the regularized training algorithm can be applied for the kernel interpretations too, which results in a network with significantly improved approximation capabilities. PMID- 17278567 TI - A novel evolutionary approach for optimizing content-based image indexing algorithms. AB - Optimization of content-based image indexing and retrieval (CBIR) algorithms is a complicated and time-consuming task since each time a parameter of the indexing algorithm is changed, all images in the database should be indexed again. In this paper, a novel evolutionary method called evolutionary group algorithm (EGA) is proposed for complicated time-consuming optimization problems such as finding optimal parameters of content-based image indexing algorithms. In the new evolutionary algorithm, the image database is partitioned into several smaller subsets, and each subset is used by an updating process as training patterns for each chromosome during evolution. This is in contrast to genetic algorithms that use the whole database as training patterns for evolution. Additionally, for each chromosome, a parameter called age is defined that implies the progress of the updating process. Similarly, the genes of the proposed chromosomes are divided into two categories: evolutionary genes that participate to evolution and history genes that save previous states of the updating process. Furthermore, a new fitness function is defined which evaluates the fitness of the chromosomes of the current population with different ages in each generation. We used EGA to optimize the quantization thresholds of the wavelet-correlogram algorithm for CBIR. The optimal quantization thresholds computed by EGA improved significantly all the evaluation measures including average precision, average weighted precision, average recall, and average rank for the wavelet-correlogram method. PMID- 17278568 TI - The ideal free distribution: theory and engineering application. AB - We extend the theory of the "ideal free distribution" (IFD) from theoretical ecology by providing methods to analytically find the distribution for a relatively general class of "suitability" functions. We show that the resulting IFD is a Nash equilibrium and an evolutionarily stable strategy (ESS). Moreover, we show that for a certain cost function it is a global optimum point. We introduce the "replicator dynamics" for the IFD and show that we provide an allocation strategy that is guaranteed to achieve the IFD. Finally, we show how this allocation strategy can achieve an IFD for a multizone temperature control problem that corresponds to achieving the maximum uniform temperature on a grid under a multivariable saturation constraint. PMID- 17278569 TI - Learning automata-based solutions to the nonlinear fractional knapsack problem with applications to optimal resource allocation. AB - This paper considers the nonlinear fractional knapsack problem and demonstrates how its solution can be effectively applied to two resource allocation problems dealing with the World Wide Web. The novel solution involves a "team" of deterministic learning automata (LA). The first real-life problem relates to resource allocation in web monitoring so as to "optimize" information discovery when the polling capacity is constrained. The disadvantages of the currently reported solutions are explained in this paper. The second problem concerns allocating limited sampling resources in a "real-time" manner with the purpose of estimating multiple binomial proportions. This is the scenario encountered when the user has to evaluate multiple web sites by accessing a limited number of web pages, and the proportions of interest are the fraction of each web site that is successfully validated by an HTML validator. Using the general LA paradigm to tackle both of the real-life problems, the proposed scheme improves a current solution in an online manner through a series of informed guesses that move toward the optimal solution. At the heart of the scheme, a team of deterministic LA performs a controlled random walk on a discretized solution space. Comprehensive experimental results demonstrate that the discretization resolution determines the precision of the scheme, and that for a given precision, the current solution (to both problems) is consistently improved until a nearly optimal solution is found--even for switching environments. Thus, the scheme, while being novel to the entire field of LA, also efficiently handles a class of resource allocation problems previously not addressed in the literature. PMID- 17278570 TI - Group decision-making model with incomplete fuzzy preference relations based on additive consistency. AB - In decision-making problems there may be cases in which experts do not have an in depth knowledge of the problem to be solved. In such cases, experts may not put their opinion forward about certain aspects of the problem, and as a result they may present incomplete preferences, i.e., some preference values may not be given or may be missing. In this paper, we present a new model for group decision making in which experts' preferences can be expressed as incomplete fuzzy preference relations. As part of this decision model, we propose an iterative procedure to estimate the missing information in an expert's incomplete fuzzy preference relation. This procedure is guided by the additive-consistency (AC) property and only uses the preference values the expert provides. The AC property is also used to measure the level of consistency of the information provided by the experts and also to propose a new induced ordered weighted averaging (IOWA) operator, the AC-IOWA operator, which permits the aggregation of the experts' preferences in such a way that more importance is given to the most consistent ones. Finally, the selection of the solution set of alternatives according to the fuzzy majority of the experts is based on two quantifier-guided choice degrees: the dominance and the nondominance degree. PMID- 17278571 TI - An active vision system for multitarget surveillance in dynamic environments. AB - This paper presents a novel agent-based method for the dynamic coordinated selection and positioning of active-vision cameras for the simultaneous surveillance of multiple objects-of-interest as they travel through a cluttered environment with a-priori unknown trajectories. The proposed system dynamically adjusts not only the orientation but also the position of the cameras in order to maximize the system's performance by avoiding occlusions and acquiring images with preferred viewing angles. Sensor selection and positioning are accomplished through an agent-based approach. The proposed sensing-system reconfiguration strategy has been verified via simulations and implemented on an experimental prototype setup for automated facial recognition. Both simulations and experimental analyses have shown that the use of dynamic sensors along with an effective online dispatching strategy may tangibly improve the surveillance performance of a sensing system. PMID- 17278572 TI - A real-time gaze position estimation method based on a 3-D eye model. AB - This paper proposes a new gaze-detection method based on a 3-D eye position and the gaze vector of the human eyeball. Seven new developments compared to previous works are presented. First, a method of using three camera systems, i.e., one wide-view camera and two narrow-view cameras, is proposed. The narrow-view cameras use autozooming, focusing, panning, and tilting procedures (based on the detected 3-D eye feature position) for gaze detection. This allows for natural head and eye movement by users. Second, in previous conventional gaze-detection research, one or multiple illuminators were used. These studies did not consider specular reflection (SR) problems, which were caused by the illuminators when working with users who wore glasses. To solve this problem, a method based on dual illuminators is proposed in this paper. Third, the proposed method does not require user-dependent calibration, so all procedures for detecting gaze position operate automatically without human intervention. Fourth, the intrinsic characteristics of the human eye, such as the disparity between the pupillary and the visual axes in order to obtain accurate gaze positions, are considered. Fifth, all the coordinates obtained by the left and right narrow-view cameras, as well as the wide-view camera coordinates and the monitor coordinates, are unified. This simplifies the complex 3-D converting calculation and allows for calculation of the 3-D feature position and gaze position on the monitor. Sixth, to upgrade eye-detection performance when using a wide-view camera, the adaptive selection method is used. This involves an IR-LED on/off scheme, an AdaBoost classifier, and a principle component analysis method based on the number of SR elements. Finally, the proposed method uses an eigenvector matrix (instead of simply averaging six gaze vectors) in order to obtain a more accurate final gaze vector that can compensate for noise. Experimental results show that the root mean square error of gaze detection was about 0.627 cm on a 19-in monitor. The processing speed of the proposed method (used to obtain the gaze position on the monitor) was 32 ms (using a Pentium IV 1.8-GHz PC). It was possible to detect the user's gaze position at real-time speed. PMID- 17278573 TI - High-performance object tracking and fixation with an online neural estimator. AB - Vision-based target tracking and fixation to keep objects that move in three dimensions in view is important for many tasks in several fields including intelligent transportation systems and robotics. Much of the visual control literature has focused on the kinematics of visual control and ignored a number of significant dynamic control issues that limit performance. In line with this, this paper presents a neural network (NN)-based binocular tracking scheme for high-performance target tracking and fixation with minimum sensory information. The procedure allows the designer to take into account the physical (Lagrangian dynamics) properties of the vision system in the control law. The design objective is to synthesize a binocular tracking controller that explicitly takes the systems dynamics into account, yet needs no knowledge of dynamic nonlinearities and joint velocity sensory information. The combined neurocontroller-observer scheme can guarantee the uniform ultimate bounds of the tracking, observer, and NN weight estimation errors under fairly general conditions on the controller-observer gains. The controller is tested and verified via simulation tests in the presence of severe target motion changes. PMID- 17278574 TI - Self-organized coordinated motion in groups of physically connected robots. AB - An important goal of collective robotics is the design of control systems that allow groups of robots to accomplish common tasks by coordinating without a centralized control. In this paper, we study how a group of physically assembled robots can display coherent behavior on the basis of a simple neural controller that has access only to local sensory information. This controller is synthesized through artificial evolution in a simulated environment in order to let the robots display coordinated-motion behaviors. The evolved controller proves to be robust enough to allow a smooth transfer from simulated to real robots. Additionally, it generalizes to new experimental conditions, such as different sizes/shapes of the group and/or different connection mechanisms. In all these conditions the performance of the neural controller in real robots is comparable to the one obtained in simulation. PMID- 17278575 TI - Adaptive critic designs for discrete-time zero-sum games with application to H(infinity) control. AB - In this correspondence, adaptive critic approximate dynamic programming designs are derived to solve the discrete-time zero-sum game in which the state and action spaces are continuous. This results in a forward-in-time reinforcement learning algorithm that converges to the Nash equilibrium of the corresponding zero-sum game. The results in this correspondence can be thought of as a way to solve the Riccati equation of the well-known discrete-time H(infinity) optimal control problem forward in time. Two schemes are presented, namely: 1) a heuristic dynamic programming and 2) a dual-heuristic dynamic programming, to solve for the value function and the costate of the game, respectively. An H(infinity) autopilot design for an F-16 aircraft is presented to illustrate the results. PMID- 17278577 TI - A wavelet-chaos methodology for analysis of EEGs and EEG subbands to detect seizure and epilepsy. AB - A wavelet-chaos methodology is presented for analysis of EEGs and delta, theta, alpha, beta, and gamma subbands of EEGs for detection of seizure and epilepsy. The nonlinear dynamics of the original EEGs are quantified in the form of the correlation dimension (CD, representing system complexity) and the largest Lyapunov exponent (LLE, representing system chaoticity). The new wavelet-based methodology isolates the changes in CD and LLE in specific subbands of the EEG. The methodology is applied to three different groups of EEG signals: 1) healthy subjects; 2) epileptic subjects during a seizure-free interval (interictal EEG); 3) epileptic subjects during a seizure (ictal EEG). The effectiveness of CD and LLE in differentiating between the three groups is investigated based on statistical significance of the differences. It is observed that while there may not be significant differences in the values of the parameters obtained from the original EEG, differences may be identified when the parameters are employed in conjunction with specific EEG subbands. Moreover, it is concluded that for the higher frequency beta and gamma subbands, the CD differentiates between the three groups, whereas for the lower frequency alpha subband, the LLE differentiates between the three groups. PMID- 17278576 TI - Sensory feedback in a half-center oscillator model. AB - We hypothesize that one role of sensorimotor feedback for rhythmic movements in biological organisms is to synchronize the frequency of movements to the mechanical resonance of the body. Our hypothesis is based on recent studies that have shown the advantage of moving at mechanical resonance and how such synchronization may be possible in biology. We test our hypothesis by developing a physical system that consists of a silicon-neuron central pattern generator (CPG), which controls the motion of a beam, and position sensors that provide feedback information to the CPG. The silicon neurons that we use are integrated circuits that generate neural signals based on the Hodgkin-Huxley dynamics. We use this physical system to develop a model of the interaction between the sensory feedback and the complex dynamics of the neurons to create the closed loop system behavior. This model is then used to describe the conditions under which our hypothesis is valid and the general effects of sensorimotor feedback on the rhythmic movements of this system. PMID- 17278578 TI - Epileptic seizure detection using genetically programmed artificial features. AB - Patient-specific epilepsy seizure detectors were designed based on the genetic programming artificial features algorithm, a general-purpose, methodic algorithm comprised by a genetic programming module and a k-nearest neighbor classifier to create synthetic features. Artificial features are an extension to conventional features, characterized by being computer-coded and may not have a known physical meaning. In this paper, artificial features are constructed from the reconstructed state-space trajectories of the intracranial EEG signals intended to reveal patterns indicative of epileptic seizure onset. The algorithm was evaluated in seven patients and validation experiments were carried out using 730.6 hr of EEG recordings. The results with the artificial features compare favorably with previous benchmark work that used a handcrafted feature. Among other results, 88 out of 92 seizures were detected yielding a low false negative rate of 4.35%. PMID- 17278580 TI - Heart sound cancellation based on multiscale products and linear prediction. AB - This paper presents a novel method for Heart Sound (HS) cancellation from Lung Sound (LS) records. The method uses the multiscale product of the wavelet coefficients of the original signal to detect HS-included segments. Once the HS segments are identified, the method removes them from the wavelet coefficients at every level and estimates the created gaps by using a set of linear prediction filters. It is shown that if the segment to be predicted is stationary, a final record with no audible artifacts such as clicks can be reconstructed using this approach. The results were promising for HS removal from LS records and showed no hampering of the main components of the LS. The results were confirmed both qualitatively by listening to the reconstructed signal and quantitatively by spectral analysis. PMID- 17278579 TI - Pattern recognition of sleep in rodents using piezoelectric signals generated by gross body movements. AB - Current research on sleep using experimental animals is limited by the expense and time-consuming nature of traditional EEG/EMG recordings. We present here an alternative, noninvasive approach utilizing piezoelectric films configured as highly sensitive motion detectors. These film strips attached to the floor of the rodent cage produce an electrical output in direct proportion to the distortion of the material. During sleep, movement associated with breathing is the predominant gross body movement and, thus, output from the piezoelectric transducer provided an accurate respiratory trace during sleep. During wake, respiratory movements are masked by other motor activities. An automatic pattern recognition system was developed to identify periods of sleep and wake using the piezoelectric generated signal. Due to the complex and highly variable waveforms that result from subtle postural adjustments in the animals, traditional signal analysis techniques were not sufficient for accurate classification of sleep versus wake. Therefore, a novel pattern recognition algorithm was developed that successfully distinguished sleep from wake in approximately 95% of all epochs. This algorithm may have general utility for a variety of signals in biomedical and engineering applications. This automated system for monitoring sleep is noninvasive, inexpensive, and may be useful for large-scale sleep studies including genetic approaches towards understanding sleep and sleep disorders, and the rapid screening of the efficacy of sleep or wake promoting drugs. PMID- 17278581 TI - Automated pediatric cardiac auscultation. AB - Most of the relevant and severe congenital cardiac malfunctions can be recognized in the neonatal period of a child's life. Misclassification of a congenital heart defect may have serious consequences on the long-term outcome of the affected child. Experienced cardiologists can usually evaluate heart murmurs with secure confidence, whereas nonspecialists, with less clinical experience, may have more difficulty. There is an acute shortage of physicians in South Africa and many rural clinics are run by nurses. Automated screening based on electronic auscultation at clinic level could therefore be of great benefit. This paper describes an automated artificial neural network as well as a direct ratio and a wavelet analysis technique, to discriminate between pathological and nonpathological heart sounds. To test the performance of the three techniques, auscultation data and electrocardiogram (ECG)-data of 163 patients, aged between 2 mo and 16 yr, were digitized. The neural network achieved a sensitivity and specificity of 90% and 96.5%, respectively, when tested with the Jack-knife method. Statistical analysis of the input to the final sigmoid function shows that a better than 99% sensitivity and specificity can be achieved if sufficient training data are available. PMID- 17278582 TI - Implantable 9-channel telemetry system for in vivo load measurements with orthopedic implants. AB - Knowledge of the loads to which orthopedic implants are subjected is a fundamental prerequisite for their optimal biomechanical design, long-term success, and improved rehabilitation outcomes. In vivo load measurements are more accurate than those obtained using mathematical musculoskeletal models. An inductively powered integrated circuit inside the implant measures six load components as well as the temperature and supplied voltage. This low-power circuit includes a 9-channel multiplexer, a programmable memory, a pulse interval modulator, and a radio-frequency transmitter. Together with a few passive components, the integrated circuit is mounted on a ceramic substrate with thick film hybrid technology. The sensor signals are multiplexed, modulated, and transmitted to an external device. The microcontroller of the external device regulates the alternating magnetic field produced by a power oscillator and synchronizes the pulse interval modulated data stream. A personal computer displays forces, moments, and temperatures in real time. The new telemetry transmitter has, thus far, been used for in vivo load measurements in three patients with shoulder endoprostheses. Eight instrumented vertebral body replacements are ready for implantation, and an instrumented tibial tray is being submitted to laboratory tests. PMID- 17278583 TI - Tracking spike-amplitude changes to improve the quality of multineuronal data analysis. AB - During extracellular electrophysiological recording experiments, the waveform of neuronal spikes recorded from a single neuron often changes. These spike-waveform changes make single-neuron identification difficult, particularly when the activities of multiple neurons are simultaneously recorded with a multichannel microelectrode, such as a tetrode or a heptode. We have developed a tracking method of individual neurons despite their changing spike amplitudes. The method is based on a bottom-up hierarchical clustering algorithm that tracks each neuron's spike cluster during temporally overlapping clustering periods. We evaluated this method by comparing spike sorting with and without cluster tracking of an identical series of multineuronal spikes recorded from monkey area TE neurons responding to a set of visual stimuli. According to Shannon's information theory, errors in spike-amplitude tracking reduce the expected value of the amount of information about a stimulus set that is transferred by the spike train of a cluster. In this study, cluster tracking significantly increased the expected value of the amount of information transferred by a spike train (p < 0.01). Additionally, the stability of the stimulus preference and that of the cross-correlation between clusters improved significantly (p < 0.000001). We conclude that cluster tracking improves the quality of multineuronal data analysis. PMID- 17278584 TI - A mu-rhythm matched filter for continuous control of a brain-computer interface. AB - A brain-computer interface (BCI) is a system that provides an alternate nonmuscular communication/control channel for individuals with severe neuromuscular disabilities. With proper training, individuals can learn to modulate the amplitude of specific electroencephalographic (EEG) components (e.g., the 8-12 Hz mu rhythm and 18-26 Hz beta rhythm) over the sensorimotor cortex and use them to control a cursor on a computer screen. Conventional spectral techniques for monitoring the continuous amplitude fluctuations fail to capture essential amplitude/phase relationships of the mu and beta rhythms in a compact fashion and, therefore, are suboptimal. By extracting the characteristic mu rhythm for a user, the exact morphology can be characterized and exploited as a matched filter. A simple, parameterized model for the characteristic mu rhythm is proposed and its effectiveness as a matched filter is examined online for a one-dimensional cursor control task. The results suggest that amplitude/phase coupling exists between the mu and beta bands during event-related desynchronization, and that an appropriate matched filter can provide improved performance. PMID- 17278585 TI - Assessment of biocompatibility of chronically implanted polyimide and platinum intrafascicular electrodes. AB - Longitudinal intrafascicular electrodes (LIFEs) are electrodes designed to be placed inside the peripheral nerve to improve stimulation selectivity and to increase the recording signal-to-noise ratio. We evaluated the functional and morphological effects of either Pt wire LIFEs or polyimide-based thin-film LIFEs implanted in the rat sciatic nerve for 3 mo. The newly designed thin-film LIFEs are more flexible, can be micromachined and allow placement of more active electrode sites than conventional Pt LIFEs. Functional results at 1 mo indicated an initial decline in the nerve conduction velocity and in the amplitude of muscle responses, which recovered during the following 2 mo towards normal values. Morphological results showed that both types of LIFEs induced a mild scar response and a focal but chronic inflammatory reaction, which were limited to a small area around the electrode placed in the nerve. Both types of LIFEs can be considered biocompatible and cause reversible, minimal nerve damage. PMID- 17278586 TI - Cerebrospinal fluid flow in the normal and hydrocephalic human brain. AB - Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity. PMID- 17278587 TI - Thermal parametric imaging in the evaluation of skin burn depth. AB - The aim of this paper is to determine the extent to which infrared (IR) thermal imaging may be used for skin burn depth evaluation. The analysis can be made on the basis of the development of a thermal model of the burned skin. Different methods such as the traditional clinical visual approach and the IR imaging modalities of static IR thermal imaging, active IR thermal imaging and active dynamic IR thermal imaging (ADT) are analyzed from the point of view of skin burn depth diagnostics. In ADT, a new approach is proposed on the basis of parametric image synthesis. Calculation software is implemented for single-node and distributed systems. The properties of all the methods are verified in experiments using phantoms and subsequently in vivo with animals with a reference histopathological examination. The results indicate that it is possible to distinguish objectively and quantitatively burns which will heal spontaneously within three weeks of infliction and which should be treated conservatively from those which need surgery because they will not heal within this period. PMID- 17278588 TI - Quantification of tremor and bradykinesia in Parkinson's disease using a novel ambulatory monitoring system. AB - An ambulatory system for quantification of tremor and bradykinesia in patients with Parkinson's disease (PD) is presented. To record movements of the upper extremities, a sensing units which included miniature gyroscopes, has been fixed to each of the forearms. An algorithm to detect and quantify tremor and another algorithm to quantify bradykinesia have been proposed and validated. Two clinical studies have been performed. In the first study, 10 PD patients and 10 control subjects participated in a 45-min protocol of 17 typical daily activities. The algorithm for tremor detection showed an overall sensitivity of 99.5% and a specificity of 94.2% in comparison to a video reference. The estimated tremor amplitude showed a high correlation to the Unified Parkinson's Disease Rating Scale (UPDRS) tremor subscore (e.g., r = 0.87, p < 0.001 for the roll axis). There was a high and significant correlation between the estimated bradykinesia related parameters estimated for the whole period of measurement and respective UPDRS subscore (e.g., r = -0.83, p < 0.001 for the roll axis). In the second study, movements of upper extremities of 11 PD patients were recorded for periods of 3-5 hr. The patients were moving freely during the measurements. The effects of selection of window size used to calculate tremor and bradykinesia related parameters on the correlation between UPDRS and these parameters were studied. By selecting a window similar to the period of the first study, similar correlations were obtained. Moreover, one of the bradykinesia related parameters showed significant correlation (r = -0.74, p < 0.01) to UPDRS with window sizes as short as 5 min. Our study provides evidence that objective, accurate and simultaneous assessment of tremor and bradykinesia can be achieved in free moving PD patients during their daily activities. PMID- 17278589 TI - Imaging electrical impedance from acoustic measurements by means of magnetoacoustic tomography with magnetic induction (MAT-MI). AB - We have conducted computer simulation and experimental studies on magnetoacoustic tomography with magnetic induction (MAT-MI) for electrical impedance imaging. In MAT-MI, the object to be imaged is placed in a static magnetic field, while pulsed magnetic stimulation is applied in order to induce eddy current in the object. In the static magnetic field, the Lorentz force acts upon the eddy current and causes acoustic vibrations in the object. The propagated acoustic wave is then measured around the object to reconstruct the electrical impedance distribution. In the present simulation study, a two-layer spherical model is used. Parameters of the model such as sample size, conductivity values, strength of the static and pulsed magnetic field, are set to simulate features of biological tissue samples and feasible experimental constraints. In the forward simulation, the electrical potential and current density are solved using Poisson's equation, and the acoustic pressure is calculated as the forward solution. The electrical impedance distribution is then reconstructed from the simulated pressure distribution surrounding the sample. The present computer simulation results suggest that MAT-MI can reconstruct conductivity images of biological tissue with high spatial resolution and high contrast. The feasibility of MAT-MI in providing high spatial resolution images containing impedance related information has also been demonstrated in a phantom experiment. PMID- 17278590 TI - Multisite recording of extracellular potentials produced by microchannel-confined neurons in-vitro. AB - Towards establishing electrical interfaces with patterned in vitro neurons, we have previously described the fabrication of hybrid elastomer-glass devices polymer-on-multielectrode array technology and obtained single-electrode recordings of extracellular potentials from confined neurons (Claverol-Tinture et al., 2005). Here, we demonstrate the feasibility of spatially localized multisite recordings from individual microchannel-guided neurites extending from microwell confined somas with good signal-to-noise ratios (20 dB) and spike magnitudes of up to 300 microV. Single-cell current source density (scCSD) analysis of the spatio-temporal patterns of membrane currents along individual processes is illustrated. PMID- 17278591 TI - Design of surface electrode array for measuring conduction velocity in the human genioglossus muscle. AB - A new appliance, incorporating linear arrays of pin electrodes for genioglossus (GG) surface electromyography measurement, is presented. This design enables the estimation of GG muscle fiber conduction velocity, which decreases with fatigue. The performance of the device was evaluated for ten healthy human subjects during fatiguing and force varying contractions. PMID- 17278592 TI - Methods of solving reduced lead systems for inverse electrocardiography. AB - In the context of inverse electrocardiography, we examine the problem of using measurements from sets of electrocardiographic leads that are smaller than the number of nodes in the associated geometric models of the torso. We compared several methods to estimate the solution from such reduced-lead measurements sets both with and without knowledge of prior statistics of the measurements. We present here simulation results that indicate that deleting rows of the forward matrix corresponding to the unmeasured leads performs best in the absence of prior statistics, and that Bayesian (or least-squares) estimation performs best in the presence of prior statistics. PMID- 17278593 TI - Comments on "algorithm for tissue ischemia estimation based on electrical impedance spectroscopy". PMID- 17278594 TI - Convert. . . A new dentist's approach to practice. PMID- 17278595 TI - AAP clarifies guidelines for management of periodontal patients. PMID- 17278596 TI - Let's relate impressioning to die trimming. PMID- 17278597 TI - Patient-centered treatment planning: part 1. PMID- 17278598 TI - Creating new face of dentistry: dental spas. PMID- 17278599 TI - Rediscovering the artistic beauty of dentistry with porcelain veneers. PMID- 17278600 TI - A new smile for a new life. AB - In this article we have shown that with meticulous planning, proper preparation, and good communication, state-of-the-art dentistry can be performed (Figure 14). Our attention to detail in every aspect of this case provided us with exceptional results. By using the Captek crowns as an alternative to conventional porcelain fused-to-metal crowns, we were able to provide this beautiful young woman with both a functional and aesthetically pleasing smile. PMID- 17278601 TI - Antimicrobial host response therapy in periodontics: a modern way to manage disease, part 2. PMID- 17278602 TI - Immediate placement and immediate loading of implants: restoring a smile in one day. PMID- 17278603 TI - From root canal to art form achieving transcendence. PMID- 17278604 TI - Clinically enhancing the connection between endodontic and restorative treatment for better case prognosis. AB - This article focuses on the endodontic-restorative interface. The reduction of bacterial contamination via chemical-mechanical debridement during conventional endodontic treatment, in conjunction with canal obturation and timely restorative treatment using a rubber dam to prevent the microbial recontamination of the canal system, will significantly improve the clinical outcome. PMID- 17278606 TI - Implementing a crown service policy in your practice. PMID- 17278605 TI - Managing stress with composite resin, part 2: the class V restoration. PMID- 17278607 TI - Selecting new technologies and equipment: a decision-making process. PMID- 17278608 TI - Ten commonly asked computer questions. . . and answers: part 2. PMID- 17278609 TI - [Neonatal diarrhoea in pigs: alpha- and beta2-toxin produced by Clostridium perfringens]. AB - Since 2001 the Pig Health Unit of Utrecht University has been consulted by various pig farms regarding neonatal diarrhoea. When preventive measures against E. coli-induced diarrhoea had no or limited results, the diarrhoeic piglets were investigated further. The microbiological and pathological findings were indicative of infection with Clostridium perfringens. Toxin typing by polymerase chain reaction led to the detection of genes encoding a-toxin (cpa) and beta2 toxin (cpb2). Surprisingly, alpha- and beta2-toxin-producing C. perfringens was isolated from all tested herds with piglets with neonatal diarrhoea. From our observations, it is likely that many herds in the Netherlands are infected with beta2-toxin-producing C. perfringens strains. As present vaccines lack beta2 toxoid and thus do not provide piglets with protection against beta2-induced diarrhoea. PMID- 17278610 TI - [Sporotrichosis in a cat and it's owner]. PMID- 17278611 TI - [Professional teeth cleaning is more than plaque removal]. AB - Telephone enquiries about the cost of cleaning the teeth of cats or dogs cannot be answered without clinical investigation of the animal and oral examination under sedation or anaesthesia. This article describes the procedures used during the professional cleaning of the teeth of companion animals. An itemized list of procedures and their cost means that the era of "shopping around" for teeth cleaning is past. PMID- 17278612 TI - [Screaming like a......]. PMID- 17278613 TI - [Judgement on the self vaccination of swine rule]. PMID- 17278614 TI - [Research priorities of the MRSA problem in the Dutch animal husbandry]. PMID- 17278615 TI - [Equine atypical myopathy]. PMID- 17278616 TI - [Reaction to "Professional Rabbit"]. PMID- 17278617 TI - Maximum-likelihood variance components analysis of heritabilities of cranial nonmetric traits. AB - Nonmetric traits of the cranium are often used to support hypotheses of the history and divergence of human populations. These studies rely on the assumption that nonmetric traits are heritable, yet few skeletal series exist with associated pedigree information that allow for the calculation of additive genetic variance, or heritability. In addition, traits for which heritabilities have been published represent dichotomous present/absent forms instead of the range of expression that can be observed for many nonmetric characters. In the present study I use a maximum-likelihood variance components analysis to calculate univariate narrow-sense heritability estimates on the skeletal series from Hallstatt, Austria, for 9 sutural bones, 27 multilevel traits, and dichotomized present/absent forms for 19 of these multilevel characters. Most of the trait heritabilities do not differ significantly from a model of h2 = 0, and they have large standard errors. In a heuristic comparison of multilevel versus dichotomous trait forms, most of the nonmetric characters showed no differences in heritability between the two methods used for parsing the phenotypic variation, although where differences were noted, the presence-absence version had higher heritabilities. These results have implications not only for the use of particular nonmetric traits in population studies but also for the practice of character dichotomization in data collection. PMID- 17278618 TI - Ethnic differences in the prevalence of inherited thrombophilic polymorphisms in an asymptomatic Australian prenatal population. AB - Differences in the prevalence of thrombophilias in different ethnic populations have been demonstrated. Because the Australian population includes many different ethnic groups, we sought to assess the effect of ethnicity in our Australian prenatal population on the prevalence of thrombophilic polymorphisms. Asymptomatic, nulliparous women (n = 1,129) recruited for a large prospective study were included in this analysis. These women had no personal or family history of venous thromboembolism and were not known to be carrying an inherited or acquired thrombophilia. Ethnicity was determined at recruitment, and women were categorized as being of Northern European, Southern European, Middle Eastern, Asian, or Other ethnicity. These women underwent genotyping for the following polymorphisms: factor V Leiden G1691A, prothrombin gene A20210G mutation, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and thrombomodulin C1418T. The factor V Leiden allele was seen significantly more frequently in patients of Middle Eastern background compared to those of Northern European and Asian ethnicity (p < 0.05). The prothrombin gene mutation was seen significantly more frequently in patients of Southern European ethnicity compared to those of Northern European or Asian ethnicity (p < 0.05). The MTHFR C677T allele (mutant) was significantly less common in those of Asian ethnicity compared to patients of Northern European and Southern European ethnicity (p < 0.0005). There were no significant differences seen with the MTHFR A1298C polymorphism. The mutant thrombomodulin allele was seen significantly more frequently in Asian women compared to Northern European, Southern European, or Middle Eastern women (p < 0.005). There are important ethnic differences in the prevalence of thrombophilic polymorphisms in the Australian prenatal population. PMID- 17278619 TI - Reanalysis of Eurasian population history: ancient DNA evidence of population affinities. AB - Mitochondrial hypervariable region I genetic data from ancient populations at two sites in Asia-Linzi in Shandong (northern China) and Egyin Gol in Mongolia-were reanalyzed to detect population affinities. Data from 51 modern populations were used to generate distance measures (Fst's) to the two ancient populations. The tests first analyzed relationships at the regional level and then compiled the top regional matches for an overall comparison to the two probe populations. The reanalysis showed that the Egyin Gol and Linzi populations have clear distinctions in genetic affinity. The Egyin Gol population as a whole appears to bear close affinities with modern populations of northern East Asia. The Linzi population seems to have some genetic affinities with the West, as suggested by the original analysis, although the original attribution of "European-like" seems to be misleading. We suggest that the Linzi individuals are potentially related to early Iranians, who are thought to have been widespread in parts of Central Eurasia and the steppe regions in the first millennium B.C., although some significant admixture between a number of populations of varying origin cannot be ruled out. We also examine the effect of sequence length on this type of genetic data analysis and discuss the results of previous studies on the Linzi sample. PMID- 17278621 TI - Genetic structure of Dagestan populations: a study of 11 Alu insertion polymorphisms. AB - We examined genetic variation in nine populations of Dagestan using 11 autosomal Alu insertion polymorphisms to investigate the genetic structure of indigenous groups and to assess their genetic relationship with world populations. Genetic differentiation among mountain inhabitants (Gsr = 2%) is comparable to that for European populations. Traces of genetic drift are detectable only for endogamous and small Ando-Dido-speaking ethnic groups, and they coincide with the most linguistically diverse region of Dagestan. Multidimensional scaling analyses among West Eurasian populations revealed that mountain inhabitants of Dagestan are closely related to Anatolian and Cyprus Turks. Thus our frequency data are consistent with the available Y-chromosome data, according to which the Middle East and the Caucasus share a considerable portion of the gene pool. Overall, our results corroborate the initially suggested genetic contribution of Middle Eastern populations to Caucasus populations. PMID- 17278620 TI - Genetic structure in contemporary south Tyrolean isolated populations revealed by analysis of Y-chromosome, mtDNA, and Alu polymorphisms. AB - Most of the inhabitants of South Tyrol in the eastern Italian Alps can be considered isolated populations because of their physical separation by mountain barriers and their sociocultural heritage. We analyzed the genetic structure of South Tyrolean populations using three types of genetic markers: Y-chromosome, mitochondrial DNA (mtDNA), and autosomal Alu markers. Using random samples taken from the populations of Val Venosta, Val Pusteria, Val Isarco, Val Badia, and Val Gardena, we calculated genetic diversity within and among the populations. Microsatellite diversity and unique event polymorphism diversity (on the Y chromosome) were substantially lower in the Ladin-speaking population of Val Badia compared to the neighboring German-speaking populations. In contrast, the genetic diversity of mtDNA haplotypes was lowest for the upper Val Venosta and Val Pusteria. These data suggest a low effective population size, or little admixture, for the gene pool of the Ladin-speaking population from Val Badia. Interestingly, this is more pronounced for Ladin males than for Ladin females. For the pattern of genetic Alu variation, both Ladin samples (Val Gardena and Val Badia) are among the samples with the lowest diversity. An admixture analysis of one German-speaking valley (Val Venosta) indicates a relatively high genetic contribution of Ladin origin. The reduced genetic diversity and a high genetic differentiation in the Rhaetoroman- and German-speaking South Tyrolean populations may constitute an important basis for future medical genetic research and gene mapping studies in South Tyrol. PMID- 17278622 TI - MtDNA variation in the Altai-Kizhi population of southern Siberia: a synthesis of genetic variation. AB - The native peoples of Gorno Altai in southern Siberia represent a genetically diverse population and have been of great interest to anthropological genetics. In particular, the southern Altaian population is argued to be the best candidate for the New World ancestral population. In this study we sampled Altai-Kizhi from the southern Altaian village of Mendur-Sokkon, analyzed mtDNA RFLP markers and HVS-I sequences, and compared the results to other published mtDNA data from Derenko et al. (2003) and Shields et al. (1993) encompassing the same region. Because each independent study uses different sampling techniques in characterizing gene pools, in this paper we explore the accuracy and reliability of evolutionary studies on human populations. All the major Native American haplogroups (A, B, C, and D) were identified in the Mendur-Sokkon sample, including a single individual belonging to haplogroup X. The most common mtDNA lineages are C (35.7%) and D (13.3%), which is consistent with the haplogroup profiles of neighboring Siberian groups. The Mendur-Sokkon sample exhibits depressed HVS-I diversity values and neutrality test scores, which starkly differs from the Derenko et al. (2003) data set and more closely resembles the results for neighboring south Siberian groups. Furthermore, the multidimensional scaling plot of DA genetic distances does not cluster the Altai samples, showing different genetic affinities with various Asian groups. The findings underscore the importance of sampling strategy in the reconstruction of evolutionary history at the population level. PMID- 17278623 TI - Evolution of inbreeding coefficients and effective size in the population of Saguenay Lac-St.-Jean (Quebec). AB - We computed mean inbreeding coefficients (FIT, FIS, and FST) based on approximately 2,700 ascending pedigrees of contemporary people from Saguenay Lac St-Jean (Quebec, Canada). This allowed us to appreciate the accumulated inbreeding and to follow the evolution of these coefficients since the founding of Quebec. One of the results was the expected increase in FST. Relying on this parameter, we computed the effective size (Ne) of the contemporary population, obtaining a value around 1,000, in agreement with previous estimations. We noticed a decrease of Ne through history despite the population's growing size. PMID- 17278624 TI - Polymorphism of the APOE locus in the Azores Islands (Portugal). AB - Our aim in this study is to report on the polymorphism of the APOE gene in the Azores Islands (Portugal) to obtain a population baseline of the existing variation in this locus, known to be one of the genetic determinants of plasma lipid levels. One hundred twenty-six Azorean individuals were typed for the APOE polymorphism using standard PCR-RFLP. Allele frequencies obtained for APOE*2, APOE*3, and APOE*4 were 6.75%, 83.73%, and 9.52%, respectively. The APOE*3/*3 genotype presented the highest frequency (69.84%), and the APOE*4/*4 genotype had the lowest frequency (0.79%). Genotype frequencies were in conformity with Hardy Weinberg expectations. The observed genotype and allele frequencies were similar to those reported for other Iberian samples. Furthermore, Nei's gene diversity (H = 0.2864 +/- 0.0351) was similar to that reported for samples from mainland Portugal. The data generated from this study will be of importance in the context of ongoing studies concerning the factors that influence lipid levels in the Azorean population. PMID- 17278625 TI - HLA class I antigen and HLA-A, -B, and -C haplotype frequencies in Uruguayans. AB - HLA class I antigens were determined for 959 unrelated Uruguayans. The predominant HLA alleles were A2, Cw4, and B35, and the most frequently observed two-loci haplotypes were A2-B44 and B35-Cw4. The most frequent three-loci HLA haplotype was A2-Cw5-B44. We compared the Uruguayan sample with similar data from other populations. PMID- 17278626 TI - Before your move--get moving! PMID- 17278627 TI - Clinical evaluation of total-etch and self-etch bonding systems for preventing sensitivity in Class 1 and Class 2 restorations. AB - The author conducted an in vivo investigation to compare the clinical performance of 4 commercial bonding agents on postoperative sensitivity. Restorations in this study were limited to Class I and Class II lesions. The patient pool consisted of 36 patients and 72 teeth (2 teeth per patient) with either a Class I or Class II lesion > 1 mm in depth present in both teeth. The 4 adhesives tested in this study were distributed among patients as follows: on the first tooth, 12 patients received an application of adhesive 1, 12 received adhesive 2, and 12 received adhesive 3. All 36 patients received an application of adhesive 4 on the second tooth. All lesions were restored using a submicron particle hybrid composite. One day and 1-week recall evaluations to measure sensitivity were taken by administrative staff in-office and by telephone. An independent clinician assessed the 1-month recall of each patient with the patient present in a clinical setting. No statistically significant differences were seen among the groups at any recall interval; however, the fourth adhesive performed consistently better than the other 3 at all intervals. All 4 bonding agents performed with clinically acceptable outcomes after a 30-day period. Certain lesion, tooth, and patient characteristics may predispose restorations to sensitivity. PMID- 17278628 TI - Enamel acid etching: a review. AB - Bonding to enamel has over 50 years of history. Efforts have been made to develop or introduce a simplified alternative, but enamel acid etching remains the most effective procedure for stable enamel bonding. Although acid etching is considered the most popular procedure in dentistry, there are characteristics that deserve special attention because of how crucial they can be in many clinical situations. This article reviews some of these aspects of enamel bonding using the acid-etching technique. PMID- 17278629 TI - Lingual nerve vulnerability: risk analysis and case report. AB - A known neurologic complication of third molar surgery is lingual nerve injury. Certain risk factors can cause lingual nerve injury during the extraction of mandibular third molars. This article will review the existing literature regarding lingual nerve injuries and related risk factors, and it attempts to study lingual nerve vulnerability during extraction of lower third molars, particularly in cases of distoangular impaction. The case report describes exposure of the lingual nerve during the extraction of the lower third molar. Also presented are 4 specific risk factors of lingual nerve injury. Recommendations are given to avoid lingual nerve trauma during removal of mandibular third molars. PMID- 17278630 TI - Properly fitted custom-made mouthguards. AB - With an increase in sporting activities comes an increase in orofacial injuries. A properly fitted mouthguard has been shown to provide protection against orofacial injuries and trauma to the teeth and supporting tissues such as the lips, cheeks, and tongue. However, because it is not mandatory that all athletes (amateur and professional) wear a mouthguard, many do not for reasons such as fit, comfort, social stigma, and speaking constraints. Athletes prefer mouthguards to be comfortable, soft, and resilient, which is characteristic of a custom-fitted mouthguard. This article will review reasons athletes prefer not to wear mouthguards and advantages of a custom-made mouthguard, as well as describe a process to fabricate a custom-made mouthguard. PMID- 17278631 TI - Q&A with Dr Don Clem. Interview. PMID- 17278632 TI - Q&A with Dr Bruce DeGinder. Interview. PMID- 17278633 TI - Achieving predictable, beautiful smiles using a dento-facial esthetic diagnosis system. PMID- 17278634 TI - [Vladimir Butureanu]. PMID- 17278635 TI - Semmelweis and hygiene: why simple solutions may fail. PMID- 17278636 TI - [Surgical relationship between France and Romania]. AB - Because 2006 is "The Year of Francophony", we considered necessary to remember the relationship between France and Romania, focusing on the surgical relationship and on the great Romanian surgeons. We talk, shortly, about the Romanian surgeons formed or specialised in France, about their contribution in the developing of Romanian surgery and the contribution of French surgeons in the developing of Romanian surgery, since 19th century. PMID- 17278637 TI - Digestive tumor bank protocol: from surgical specimens to genomic studies of digestive cancers. AB - Cancer is a complex polygenic and multifactorial disease, resulting from successive dynamic changes in the genome of somatic cells and from the accumulation of molecular alterations in both tumour cells and host cells. For the majority of cancers, including many malignancies of the gastrointestinal tract, our current means of diagnosis and treatment of the tumors are grossly insufficient. In recent years the development of several gene expression profiling methods such as comparative genomic hybridization (CGH), differential display, serial analysis of gene expression (SAGE) and DNA arrays, together with the sequencing of the human genome, has provided an opportunity to monitor and investigate the complete cascade of molecular events leading to tumor development and progression. Given the central role played by surgeons in the current management of patients with solid cancers, it is of paramount importance for them to know the principles characterizing this laboratory tools to critically assess the results originating from this biotechnology. We describe in this article the scientific partnership between Fundeni Clinical Institute Bucharest, Romania and RNtech Company, Paris, France for the development of a center of biological resources (Biobank) as well as the standardized protocol of working with the biological samples, the ongoing projects and the future perspectives. PMID- 17278638 TI - [Small bowel tumors. Clinical course and therapeutic aspects]. AB - The small bowel tumors are rare and their diagnosis is difficult. Therefore, they are usually discovered in advanced stages and often a surgical intervention is imposed due to acute complications generated by the tumors. Sometimes, they are accidentally found during other surgical procedures. We present 25 cases of small bowel tumors treated between 1996-2005. Among these cases, 4 (16%) were located in the duodenum, 10 (40%) in the jejunum and 10 (40%) in the ileum. In one case, there were multiple tumor locations spread along the mesenterial bowel and mesentery. Recently, pre- operative diagnosis has become more accurate due to modem imaging modalities, such as computed tomography, which has established the diagnosis in 12 cases. From the therapeutical perspective, the surgical intervention (spread segmentary resections/enterostomies) is the only method which improves survival rate. In our study, this approach was possible in 15 patients (60%). It was noticed that the tumor recurrences are frequent and occur early. Post-operative morbidity (12 cases--48%) and mortality (3 cases--12%) rates remain rather high. PMID- 17278640 TI - [194 laparoscopic cholecystectomy. Anesthetic and surgical details]. AB - In this clinic and prospective study we investigated the anesthetic and surgical particularities in laparoscopic cholecystectomy for 194 patients. Approximately the two third of patients have had a great mortality risk (ASA III and IV). 139 patients have had severe comorbid conditions. All patients were under general anesthesia with oro-tracheal intubation. The surgical time was between 27 and 148 minutes. The subjects of this study were old patients with acute cholecystitis and severe comorbid conditions. No significant incident or complication were noted, all patients have had a good outcome. PMID- 17278639 TI - [Conservative management in blunt splenic trauma]. AB - We reviewed for analysis the charts of two groups of adults patients with blunt splenic injuries issued from two University Hospital Centers; the group 1 (G1) of 22 patients and the group 2 (G2) of 20 patients. The results of actually therapeutic procedures concerning blunt splenic injuries and subsequently the effectiveness of non operative treatment were evaluated. Splenectomy was performed in G1 for 11 patients, instead of 19 patients in G2 (p = 0.0003), whereas, the non surgical treatment was done in 9 patients and 1 patient, respectively (p = 0.02). The mean Splenic Injury Score (SIS) was 2,95 in G1 and 3.47 in G2 (p = 0.03). The spleen was preserved in G1 for 8 patients, instead 1 patient in G2 (p = 0.04). In G1, the non operative treatment was successfully accomplished in 66% of patients. It was obtained with lack of mortality, with a lower overall morbidity and a lower length of hospital stay than in splenectomized patients, but the latter group accounted higher values of Injury Severity Scores (p < 0.05). If proper selection criteria for non operative management are used, more than a third of patients with blunt splenic injury can be treated by splenic preservation at least as safely as splenectomized patients. PMID- 17278641 TI - [Flexible ureteroscopic approach in upper urinary tract pathology]. AB - In many prestigious centers, flexible ureteroscopy (FU) has rapidly evolved into a routine application. Our goal was to evaluate the efficiency of FU in upper urinary tract pathology. Between October 2002 and January 2006, 106 patients underwent FU for upper urinary tract pathology: retrograde (23 for diagnosis, 7 for follow up after conservative treatment of upper urinary tract TCC and 67 therapeutical) and antegrade (9 cases) procedures. Therapeutical retrograde FU was indicated for: stones (59 cases), symptomatic pyelocaliceal diverticulum with intra-diverticular lithiasis (7 cases) and pyelocaliceal TCC (3 cases). Antegrade FU was performed 9 cases with ureteral or uretero-enteric strictures. In all cases we used a 7.5F Storz flexible ureteroscope. As energy sources we used Nd:YAG laser and an electrohydraulic lithotripsy device. Diagnosis retrograde FU identified upper urinary tract abnormalities in 95.7%. In the patients with lithiasis, the procedure was considered a success if complete stone clearance or lithotripsy in fragments smaller than 3 mm was achieved. The over-all success rate in these cases was 72.7%. In 57.1% with pyelocaliceal diverticula laser incision of the narrow isthmus was practiced, followed by electrohydraulic lithotripsy of the stones. All the 4 cases were stone-free at the end of the procedure. In 66.7% of patient with TCC, evaluation at 6 and 12 and 18 months demonstrated no tumoral recurrence. In 77.8% patients with ureteral or uretero enteric strictures who underwent antegrade FU, postoperative evaluation at 6 and 18 months showed good results. No intra- or postoperative complications were described. According to our experience, FU could be an efficient method in upper urinary tract pathology diagnosis and treatment in selected cases. FU has opened a vista of endless limits in upper urinary tract endoscopy. PMID- 17278642 TI - [Laparoscopic hysterectomy in very large uterus]. AB - Laparoscopic hysterectomy is an efficient alternative to vaginal hysterectomy when the vaginal approach is difficult. In patients presenting very large uterus or large lateral myomas, the primary uterine arteries coagulation at their origins allow a safe laparoscopic hysterectomy. We report this surgical procedure carried out without incidents in three cases when uterus weighed more than 700 g and suggest the primary uterine arteries approach by retrograde umbilical tracking in large benign uterus. PMID- 17278643 TI - Lichtenstein tension-free repair of inguinal hernia. AB - Recurrences have been a significant problem following hernia repair. The purpose of this study was to present our experience of Lichtenstein tension-free repair of inguinal hernia. In this retrospective study, 223 inguinal hernia repairs were performed between September 2000 and August 2003 in 203 patients, using a polypropylene mesh. The main outcome measure was early and late complications and especially recurrences. There were 189 males (93.1%) and 14 females (6.9%). Inguinal hernia was indirect in 70% of cases (n=156), direct in 25% (n=56), and of the mixed type in 5% (n=11). Bilateral inguinal hernia was found in 20 patients (9.8%). 210 (94.2%) of hernias were de novo, while 13 (5.8%) were recurrences. The mean patients age was 54.3 years (range, 32-71 years). The follow-up was completed in 160 patients (78.8%) by clinical examination. The median follow-up period was 3.0 years (range, 1-5 years). Seroma and postoperative neuralgia were observed in one and 5 patients respectively. There was only one recurrence (0.4%) four years later. Lichtenstein tension-free mesh repair of inguinal hernia is a simple and safe method, with no significant early and late morbidity and achieved a method with no recurrence during the follow-up period. PMID- 17278644 TI - Limberg flap reconstruction for the treatment of pilonidal sinus disease. AB - Pilonidal disease is a common chronic disorder of the sacrococcygeal area affecting young people. Recent reports have advocated different surgical approaches, such as open or closed technique, but recurrence complicates all forms of treatment. We conducted this case review to evaluate the validity of Limberg flap reconstruction method in the treatment of chronic recurrent pilonidal disease. In the period between September 2003 and December 2004, 32 male patients with complicated/recurrent pilonidal disease were operated on using the Limberg flap reconstruction method. The patients' mean age was 26.4 + 1.6 years (range 19-47 years). All patients fared well, had a satisfactory wound healing, had minimal pain and were mobilized immediately after surgery. They stayed at hospital for 6 to 32 hours. No patient had serious wound infection or flap ischemia. They all returned to normal activity within 4 to 12 days. Follow up ranged between 14 and 28 months. No patient had recurrence during the above period. Limberg flap reconstruction has several advantages compared to the classical surgical methods for the treatment of pilonidal disease. The patients have a short hospital stay, are mobilized soon after surgery and have a minimal morbidity and recurrence rate. PMID- 17278645 TI - [Resection and reconstruction of the esophagus with a triple approach: thoracic, abdominal, cervical]. PMID- 17278646 TI - Pancreatic abscess due to perforation of duodenal diverticulum. AB - Duodenal diverticula are usually incidental findings, but some times could be complicated with inflammatory or pressures effects to pancreas tissue. We present a rare case of pancreatic abscess caused by a perforated diverticulum, arising from the distal end of the second part of the duodenum. PMID- 17278647 TI - Intussusception of efferent intragastric loop after gastrojejunostomy--an exceptional cause of high occlusion and hematemesis. AB - Jejunogastric intussusception (GI) is an extremely rare complication of gastrojejunostomy (GJS) that may appear any time after surgical intervention. Less than 200 cases have been reported so far, on very small series. Young female, 32, who 12 years ago was operated for a gastroduodenal disease that she doesn't know many details about. She presented severe pain in the superior abdominal segment posteriorly irradiated, incoercible biliary nausea followed by hematemesis. The endoscopic, imaging and biological explorations suggested a huge gastric tumor that occupied the whole stomach and was bleeding diffusely. The rapid acute evolution asked for the urgent laparotomy that emphasized: soft tumour mass, intragastrically mobile without any scar at the stomach or duodenum level; adherent to the posterior of the stomach we discovered a ball of jejunal loops that couldn't be undone. The anterior gastrotomy sets the diagnosis: JGI of the efferent loops of a GJS. We hardly managed to reduce the intussusception, without resection, the loop being absolutely viable. In order to prevent a relapse, and because the anastomosis was not justified it was taken down. JGI in a patient presenting GJS must be taken into consideration in the presence of epigastric pain that would not cease, biliary nausea followed by hematemesis and rapid deterioration of general health status. PMID- 17278648 TI - [Two steps liver resection with right portal vein ligation for two giant hemangiomas of the left and right lobes]. AB - The liver failure is one of the most life threatening complication after extensive liver resections. In resections that exceed 70% of liver parenchyma, a two steps approach with portal branch ligation is the best alternative. The aim of the paper is to present the management of a 65-year-old female admitted into hospital for two giant symptomatic liver hemangiomas in the left lobe: segment III-20 cm. and in the right lobe: segments V-VIII-19 cm, which were non resectable in the same intervention because the small amount of liver parenchyma left, and for these we decided a two steps surgery: left atypical resection with right portal vein ligation in the first step, attending 4 month for atrophy hypertrophy process, and then right typical hepatectomy for second hemangioma who practically occupied all right liver. The postoperative course, was favorable after both interventions, with 7 days postsurgery hospitalisation, despite some hepatic failure symptoms: coagulation disturbance, increasing of bilirubin and ALAT, ASAT levels, ascites. PMID- 17278649 TI - [A rare cause of peritoneal fistula]. AB - The abdominal pregnancy is an extremely rare variety of the ectopic pregnancy. The symptoms are atypical, which causes a delay in putting the diagnosis, which is established most of the times when complications appear, which are always severe, and endanger the patients lives. This paper presents a rare complication of the abdominal pregnancy, at about 6 months old, stopped in evolution, complicated by an abscess, generalised peritonitis and peritoneal fistula. The diagnosis and treatment of the abdominal ectopic pregnancy are discussed. PMID- 17278650 TI - Invasive amebiasis. AB - Digestive amoebiasis with his invasive form is an unusual pathology encountered in the temperate zone. This could lead to a life threatening complication: systemic amoebiasis. A 55-year-old male was treated successfully of systemic amoebiasis in a third referral hospital. The diagnosis was established based on epidemiology data and microscopical identification of trophozoites of Entamoeba histolytica. The amoebicidal, antibiotic and supportive treatments was firstly administrated. The clinical picture of intestinal amoebiasis raised from dysenteric syndrome to necrotizing enteritis. The bowel perforation with localized peritonitis was followed by chronic enteric fistula. Amoebic liver abscess, as the most frequent extraintestinal complication, was concomitantly diagnosed and treated. Urinary amoebiasis was considered as complication in the context of systemic dissemination: any other location could become a site of an amoebic abscess. Multidisciplinary approach was the successful key in the management of the patient, including antiparasitic therapy and antibiotic prophylaxis, intensive care and multiple surgical approaches. The diagnosis of digestive amoebiasis and systemic complication may be delayed in nonendemic areas, leading to advanced and complicated stages of the disease. The surgical approach is most efficiently to treat a large liver amoebic abscess and intraperitoneal collections. PMID- 17278652 TI - [108th French Surgery Congress and 2nd Francophone Surgery Congress, October 2-4, 2006, Paris]. PMID- 17278651 TI - [12th National Bulgarian Congress of Surgery, Sofia October 5-6, 2006]. PMID- 17278653 TI - [Third National Congress of Romanian Society for Endoscopic Surgery and other interventional techniques(ARCE), October 4-7, 2006, Timisoara]. PMID- 17278654 TI - [10th World Congress of Endoscopic Surgery, September 13-16, 2006, Berlin]. PMID- 17278655 TI - Health related quality of life (HRQL) scoring (DR-12 score) in tuberculosis- additional evaluative tool under DOTS. AB - The study was conducted among patients diagnosed as pulmonary or extra pulmonary tuberculosis attending DOTS facilities at New Delhi Tuberculosis Centre, Delhi. The objectives of the study are; to evaluate the impairment of health related quality of life in patients of tuberculosis by evolving a HRQL questionnaire (DR 12 score) and to validate the new scoring method by making serial assessments of health related quality of life of the patients during anti-tubercular therapy initially, at the end of intensive phase (IP) and at the completion of treatment. Seventy eight consecutive patients aged between 15-60 years put on DOTS treatment at New Delhi Tuberculosis Centre, Delhi were subjected to a HRQL questionnaire (DR-12 score) at 0 week, 8 weeks and at the completion of treatment. The new scoring method contained questions on twelve parameters related to symptoms, physiological, psychological and social well-being of TB patients. The patients were asked to evaluate these twelve parameters on a score of 1-3. All the individual parameters were equally weighted. The data so obtained regarding these scores was analysed using unpaired t-test, paired t-test, one way Anova test and Pearson corelation coefficient test. The patients who converted at the end of intensive phase had a significantly higher gain in scores as against, those who failed to convert even after extension of intensive phase (p=0.019). Significantly higher scores were observed among those who had a favourable outcome as against those who had unfavourable outcome at the completion of treatment (p=0.029). Thus, DR-12 score was found to have a strong construct validity and useful additional evaluative tool for patients under DOTS therapy. PMID- 17278656 TI - Larvicidal activity of the fungus Aphanomyces (oomycetes : Saprolegniales) against Culex quinquefasciatus. AB - Several species of fungi are currently being considered for operational use in the microbial control of mosquito larvae. The oomycetous fungi are the prominent ones amongst them because of their ability to complete life cycle in water. During our studies on zoosporic fungi from riverine waters of Mula and Mutha flowing through Pune City, Maharashtra, India, Aphanomyces laevis de Bary (Oomycetes: Saprolegniales) was isolated from polluted waters. After critical observations it was found to be mosquito larvicidal. Sporulating hemp seed cultures when inoculated under laboratory conditions revealed that it causes 80%/ mortality after seven days to Culex quinquefasciatus larvae. Laboratory assays were conducted to determine the effects of water quality on the ability of the isolate to infect mosquito larvae in varying degrees of pollution levels. In all the experiments, a non sexual strain of Aphanomyces (zoospores) was found to be the pathogenic agent for the Culex larvae. PMID- 17278657 TI - Epidemiology of a new focus of localized cutaneous leishmaniasis in Himachal Pradesh. AB - A new focus of localised cutaneous leishmaniasis has emerged along the Satluj River valley in the mountainous region of north west Himachal Pradesh. The main endemic region extends from Pooh subdivision of Kinnaur district to Kumarsain subdivision of Shimla district with adjoining Nirmand subdivision of Kullu District comprising 86 villages. The climate of the affected areas varies from temperate to subtropical. A total of 285 cases were recorded from 1988 to January, 2005. The age of these patients varied from 10 months to 75 years, with 63 children (<12Years), and a male to female ratio of 1: 0.9. The duration of disease was 15 days to 48 months with majority (85%) presenting between 1-6 months. The number of lesions varied from 1-8, and were mostly seen on exposed parts of the body. Morphologically, lesions were asymptomatic, dry, nodular or crusted nodulo-ulcerative plaques. Tissue smear positivity for amastigotes was 43%. The characterization of 14 strains of these Leishmania revealed presence of both Leishmania tropica (n=3) and Leishmania donovani (n=11). Identification of the 42 sandflies collected from the peridomestic environment of the patients, revealed Phlebotomus longiductus - 29, P. major 8, P. kandelaki 2, while 2 remained unidentified. The patients were treated with intralesional sodium stibogluconate and majority showed excellent response. PMID- 17278658 TI - Bacterial isolates from mechanically ventilated patients with nosocomial pneumonia within intensive care unit of a tertiary care center. AB - Nosocomial pneumonia is a common complication in mechanically ventilated patients. A study was carried out to determine the incidence, common bacterial etiologic agents and their antimicrobial susceptibility, and outcome of such pneumonia in an Intensive Care Unit (ICU) of a tertiary care center. In Surgical ICU (SICU) 176 patients required mechanical ventilation for more than 72 hours. A total of 39 (22.1%) of these patients developed nosocomial bacterial pneumonia as determined by microbiological assays. Endotracheal aspirate cultures detected a single bacterial isolate in 22 (56.4%) patients while two and three organisms were isolated from 10 (25.6%) and 7 (17.9%) patients respectively. Fifty three (84.1%) of a total of 63 isolates were Gram negative bacilli. The most frequently encountered pathogens were Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter species among the Gram negative bacilli and Staphylococcus aureus among the Gram positives. Resistance of bacterial isolates varied from 24 to 90% against commonly used antibiotics. Amikacin had the best profile, with 14% to 55% resistance against various isolates. Twenty three (59%) of 39 patients with pneumonia expired in the ICU. P. aeruginosa (25.6%) and K. pneunmoniae (17.9%) were the predominant isolates in these patients. Nosocomial pneumonia with high mortality is a frequent occurrence in mechanically ventilated patients in our ICU setting. Gram negative organisms with high levels of antimicrobial resistance are the most common isolates. Regular surveillance and monitoring of changes in antibiotic susceptibility of bacterial pathogens and appropriate therapeutic measures are likely to reduce the mortality in these patients. PMID- 17278659 TI - Surveillance of bacteriological quality of natural water resources in rural areas around Kasauli Town, Distt. Solan, Himachal Pradesh. AB - A study was conducted to find out the bacteriological quality of water during the monsoon season in local areas around Kasauli Town, and to evaluate the management of water resources in rural areas. The water samples were collected from bowries and hand pumps. As there is no municipal water supply in majority of these areas, the local residents depends mainly on these natural resources without any treatment of water. All the 14 surface water samples collected from bowries were found bacteriologically polluted with total coliform count ranging from 35-1800+. The main contaminants isolated were atypical thermotolerant E. coli, Pseudomonas fluorescence, Enterobacter cloacae, Aeromonas liquifaciens, Citrobacter freundii and Pseudomonas pseudomaleii. Among seven hand pump samples, two were found to have Coliform count 80 and 250 respectively. These two water samples were found contaminated with Citrobacter freundii and E. coli &Aeromonas liquefaciens respectively. These bacteriological contaminations appear to be both from vegetative & human or animal excreta sources. The study therefore suggested that the water from these natural resources requires treatment either by boiling or chlorination before human consumption to avoid any outbreak. PMID- 17278660 TI - Malaria control using deltamethrin impregnated mosquito nets/ insecticide treated bed nets: experience in armed forces. AB - The study was undertaken to evaluate the impact of deltamethrin-impregnated mosquito nets on malaria incidence, mosquito density, any adverse side effect among users. A field trial was carried out over a period of three years in two adjacent military stations at Allahabad (UP), keeping one as a trial and other as a control station. During first year, baseline data were collected and during next two years residual spray was replaced with use of deltamethrin impregnated mosquito nets in trial station. The use of deltamethrin-impregnated mosquito nets/insecticide treated bed nets resulted in a significant decline in malaria incidence and Annual Parasite Index (API). The average mosquito density of Anopheline mosquitoes decreased by 67.8% and Culex by 49.7%. The insecticide was found safe for use amongst troops. Use of deltamethrin-impregnated mosquito nets has beneficial impact on integrated control of malaria. PMID- 17278661 TI - An outbreak of dengue fever in Veerannapet village, Cherial Mandal, of Warangal district, Andhra Pradesh. AB - An epidemiological and entomological investigation was carried out in Veerannapet village, Cherial Mandal of Warangal district, Andhra Pradesh. The study showed that all age groups and both the sexes were affected with the disease. Fever and bodyache was the first presenting feature, which was self-limiting and lasted for 4-5 days. Of the 19 Serum Samples tested, 17 showed high titre to Dengue antigen with 10 showing diagnostic titre. Five samples were positive for IgM antibodies to dengue virus. Larval surveys indicates high Breteau index (30.40%), House index (23.20%) and Container index (9.17%). The clinico-epidemiological and entomological investigation indicates present episode of fever outbreak is due to dengue fever. Strengthening and intensification of surveillance along with educating the community is recommended for prevention of outbreak. PMID- 17278662 TI - Seroprevalence of HSV1 and HSV2 infections in family planning clinic attenders. AB - Few studies from India documented seroprevalence of HSV 1 and 2 infection in different population groups. We determined HSV 1 and 2 seroprevalence in a cohort of adults 16-40 year of age, attending the family planning clinic. For the overall study population, 63% were seropositives, 33.3% for HSV 1 alone. 16.6% for HSV 2 and 13.3% had mixed infection. By the statistical analysis, the mean age difference between the two sexes for either infection was not significant. HSV-2 seroprevalence was associated with an increasing age. Men were more likely than women to be seropositive for HSV2. More studies from India are required to coroborate our findings. PMID- 17278663 TI - Prevalence of leucorrhoea among married women in the age group of 15-44 years in a rural community. PMID- 17278664 TI - Defaulters in relation to number of doses of hepatitis B vaccination in hospital staff at S.R.T.R. Medical College, Ambajogai. PMID- 17278665 TI - Solar disinfection of drinking water. PMID- 17278666 TI - Coconut chutney : so unsafe a dish! PMID- 17278667 TI - Bangalore slums free of filarial infection ? PMID- 17278668 TI - Invasive aspergillosis in an immunocompetent host. AB - Invasive aspergillosis is an uncommon opportunistic infection usually seen in immunocompromised patients. Despite extensive therapeutic measures the outcome is usually unfavourable. We report a case of invasive aspergillosis in an immunocompetent individual. PMID- 17278669 TI - The impact of cannabis on driving. AB - BACKGROUND: Cannabis is known to have detrimental effects on human performance and may also affect driving adversely. However, studies designed to examine this issue have provided equivocal findings. We set up this study to further determine the effect of cannabis on driving. METHODS: We used a cross-sectional, case control design with drivers aged 20-49 who were involved in a fatal crash in the United States from 1993 to 2003; drivers were included if they had been tested for the presence of cannabis and had a confirmed blood alcohol concentration of zero. Cases were drivers who had at least one potentially unsafe driving action recorded in relation to the crash (e.g., speeding); controls were drivers who had no such driving action recorded. We calculated the crude and adjusted odds ratios (ORs) of any potentially unsafe driving action in drivers who tested positive for cannabis but negative for alcohol consumption. In computing for the adjusted OR, we controlled for age, sex, and prior driving record. RESULTS: Five percent of drivers tested positive for cannabis. The crude OR of a potentially unsafe action was 1.39 (99% CI = 1.21-1.59) for drivers who tested positive for cannabis. Even after controlling for age, sex, and prior driving record, the presence of cannabis remained associated with a higher risk of a potentially unsafe driving action (1.29, 99% CI = 1.11-1.50). CONCLUSION: Cannabis had a negative effect on driving, as would be predicted from human performance studies. This finding supports the need for interventions to decrease the prevalence of driving under the influence of cannabis, and indicates that further studies should be conducted to investigate the dose-response relationship between cannabis and safe driving. PMID- 17278670 TI - Nutrient intakes and food consumption patterns among Ontario students in grades six, seven, and eight. AB - BACKGROUND: The increased prevalence of overweight in Canadian children has stimulated interest in their lifestyle behaviours. The purpose of this research was to investigate dietary intake and food behaviours of Ontario students in grades six, seven, and eight. METHODS: Males and females from grades six to eight were recruited from a stratified random selection of schools from Ontario. Data were collected using the web-based "Food Behaviour Questionnaire", which included a 24-hour diet recall and food frequency questionnaire. Nutrients were analyzed using ESHA Food Processor and the 2001 Canadian Nutrient File database. Body Mass Index (BMI) was calculated based on self-reported weight and height, and classified according to the Centers for Disease Control BMI for age percentiles. RESULTS: The sample included males (n = 315) and females (n = 346) in grades 6, 7, and 8 from 15 schools in Ontario. According to Canada's Food Guide to Healthy Eating (CFGHE), median intakes were below recommendations for all participants, with the exception of meat and alternatives. Participants consumed a median of 54%, 15%, 31%, 11%, and 8% of total energy from carbohydrates, protein, total fat, saturated fat, and added sugars, respectively. Participants consumed 25% of total energy from foods from the "other" food group (CFGHE). Males had higher intakes of energy, carbohydrates, fat, saturated fat, monounsaturated fat, protein, thiamine, niacin, iron, and zinc than females (all p < 0.05), and consumed more grain products servings (p < 0.05). CONCLUSION: The high consumption of "other" foods, at the expense of nutrient-dense food groups, may ultimately be contributing to the increased weights in childhood and adolescence. PMID- 17278671 TI - Can food banks sustain nutrient requirements? A case study in Southwestern Ontario. AB - BACKGROUND: Concerns about adequate food supply is a mounting problem in Canada, making food bank visits a necessity for over 820,000 Canadians. Given this reliance, the purpose of this study was to compare contents of food hampers with Canadian guidelines, at a large urban food bank in Southwestern Ontario that intends to provide 3 days worth of food per person. METHOD: Thirty hampers of each available size (for 1-6 people) were sampled (N = 180). Food items were recorded and analyzed for caloric value, food group, and macro- and micro nutrient values. Results were compared to Dietary Reference Intakes (DRI) and Canada's Food Guide to Healthy Eating. RESULTS: 99% of hampers did not provide 3 days worth of nutrients. Grains and cereals met the lower range of Canada's Food Guide recommendations, and fruits and vegetables, meats and alternatives, and dairy products were below recommended levels, as were numerous vitamins and minerals, including vitamins A, D, B12, C, riboflavin, niacin, calcium, magnesium and zinc. Carbohydrates were slightly above recommended DRI, and energy from fat and protein scarcely met the minimums recommended. Hampers contained 1.6 days worth of energy per person. DISCUSSION: The energy available per person was below recommendations for most Canadians. Nutrients missing from the hampers can come from fresh fruits, vegetables, dairy products, and meats and alternatives. However, many low-income families have limited finances to purchase these foods which are relatively more expensive than processed foods. Encouraging more perishable food donations and storage facilities to maximize the nutritional intake for clients is imperative. PMID- 17278673 TI - Culture Connection Project: promoting multiculturalism in elementary schools. AB - OBJECTIVE: To promote multiculturalism among grade school students through drama education. PARTICIPANTS: Grade 3-6 students (N = 665) from 6 targeted schools including lead-class students (n = 158) representing each school. SETTINGS: Elementary schools in Windsor-Essex County, Ontario, Canada. INTERVENTION: In this non-experimental design study, group discussions conducted with each lead class to explore students' understanding of multiculturalism were developed into an interactive drama performance and performed for all grades 3-6 students in their respective schools. A follow-up drama workshop was offered to each lead class one week after the drama performance. All students completed a 7-item questionnaire before and after the drama performance and after the drama workshop. Pre-test and post-test data collected were analyzed using T-test and ANOVA to determine the effects of drama education on students' attitudes toward multiculturalism. OUTCOMES: Statistical analysis at 0.05 significance level revealed that both the performance and the drama workshop heightened students' awareness of racism, and instilled cultural respect through "talking with others", "accepting others", and "believing that they can make a difference" in multiculturalism promotion. CONCLUSION: Drama education was an effective experiential tool for promoting multiculturalism in a school setting. The key to promoting inter-racial harmony is to respect and accept individual differences and to broaden the social determinants of health by providing culture safety care. PMID- 17278672 TI - Global Youth Voices: engaging Bedouin youth in health promotion in the Middle East. AB - OBJECTIVE: This study evaluated the six-phase Global Youth Voices model (EIPARS) for engaging youth in community health promotion in the Middle East: 1) engagement, 2) issue identification, 3) planning, 4) action, 5) Rs; research, reflect, reward and 6) sustainability. PARTICIPANTS AND SETTING: 20 Grade 9 students (10 boys, 10 girls) from two Bedouin communities: 10 from Tuba-Zangaria in North Israel; 10 from Segev Shalom in the Negev--South Israel. INTERVENTION: Using low-end (photo-voice, photography) and high-end internet-based technology, youth identified and documented the strengths and weaknesses of their communities, and then undertook a community action project focusing on one important issue. Workbooks including process guides and tools for each step of the EIPARS model are available online at: http://www.globalyouthvoices.org/resources.html. OUTCOMES: Similar issues were identified in each community: e.g., smoking, injuries, friendships, Bedouin culture. Unique issues identified were suicide at Tuba and industrial pollution at Segev Shalom. Students at Tuba selected Suicide Prevention for a community project and prepared a PowerPoint presentation for educating their peers, teachers and parents. Youth from Segev Shalom created a video and photo exhibit on Violence Prevention. Photo-essays and their action projects were uploaded to the Global Youth Voices website for virtual discussion and sharing with youth globally (www.globalyouthvoices.org/middle-east/greetings-en.html). CONCLUSION: This project demonstrated that the EIPARS model can be used successfully for engaging youth and creating youth-driven community action in the Middle East. This public health intervention provides a positive approach for building cooperation in conflicted regions. PMID- 17278674 TI - The tobacco control community of tomorrow: a vision for training. AB - OBJECTIVE: Current and emerging public health challenges require a new approach to research training. The purpose of the CIHR-Strategic Training Program in Tobacco Research (STPTR) is to equip the next generation of scientific leaders with the knowledge, skills and experiences that will enhance their ability to conduct tobacco research that will have a positive impact on the health of the population. PARTICIPANTS: Graduate students or post-doctoral fellows from any university in Canada who are working with a STPTR Mentor in the broad area of tobacco control. SETTING: Mentors at three universities: University of British Columbia, University of Toronto, and University of Waterloo. INTERVENTION: The STPTR currently has four elements: a video course linking STPTR trainees and mentors across universities; an annual meeting; stipend awards that free CIHR STPTR fellows to concentrate on research; and personal, cross-disciplinary research mentoring. OUTCOMES: Feedback solicited from current and past trainees at the three-year point of the program suggests that there are four key value added benefits associated with being a trainee in the STPTR: transdisciplinary connectedness, community building, capacity building, and exposure. CONCLUSION: Feedback from trainees at different stages in their training experience, different academic institutions, and different academic disciplines will inform the ongoing framing of the STPTR and may inform future training programs in other disciplines of chronic disease prevention, health promotion, and the emerging science of population-level intervention. PMID- 17278675 TI - [Treatment retention and evolution of clientele in a low threshold methadone substitution treatment program in Montreal]. AB - OBJECTIVES: To evaluate client treatment retention and evolution in terms of living conditions, at-risk behaviours, and the use of psychoactive substances (PAS) over a one-year period, following admission into a low-threshold methadone program in Montreal. METHOD: Individual interviews were administered to 114 clients from Relais-Methadone (RM) at admission and one year after treatment initiation. Participants reported on PAS consumption and unsafe practices of drug use and sexual behaviours at high risk for transmission of HIV, sexually transmitted infections (STI) and other blood-borne viruses (BBV). Services utilized by clients were documented from Relais-Methadone files. Bivariate analyses were used to compare data recorded at admission and one-year follow-up. RESULTS: The treatment retention rate after one year at RM was 64%. However, by taking into account those clients who were transferred to a regular program during the study period, as well as those who voluntarily tapered their methadone treatment (16.7%), the status of 80.7% of clients demonstrated improvement one year after admission into treatment. Furthermore, the clients who remained in treatment for a year for whom information was available (n = 60) showed a tendency towards more stable living conditions. They also demonstrated a significant decrease in both the number of PAS injections and in risky behaviours related to drug consumption. A statistically significant decrease in the frequency of heroine and cocaine use was also observed. By contrast, however, two thirds of the individuals in treatment after a year (n = 42) maintained or increased their daily consumption of other PAS. DISCUSSION: The treatment retention rate is comparable to other low or regular threshold substitution programs. The results support previous studies showing that the methadone substitution treatment reduces heroine and cocaine consumption, and decreases the number of unsafe behaviours that could potentially transmit HIV, STI and BBV for the majority of clients who remained in treatment. Future research could focus attention on people who abandon treatment and those who present at-risk behaviours during treatment. PMID- 17278676 TI - Participant-collected, mail-delivered oral fluid specimens can replace traditional serosurveys: a demonstration-of-feasibility survey of hepatitis A virus-specific antibodies in adults. AB - BACKGROUND: Although population-based serosurveys offer an optimal measure of cumulative infection rates, they are seldom performed due to high cost and complex logistics. Use of participant self-collected oral fluid as a diagnostic specimen and mail for specimen delivery has the potential of generating reliable, population-representative data at limited cost. METHODS: A survey of oral fluid HAV-specific immunoglobulin G (an indicator of past HAV infection) was undertaken in a provincially representative sample of 20-39 year olds as a pilot study. A provincial administrative database served as the sampling frame. Potential participants were invited by mail to collect oral fluid and complete a questionnaire at home and return both by mail. Additional telephone prompting was directed at slow responders. Oral fluid was tested using a validated ELISA. RESULTS: From among 2,448 potential participants, contact by mail or telephone was made with 1,009 eligible subjects; 59% (585) participated. Materials withstood mailing and the quality of self-collected specimens was excellent. A positive test result was found in 22.1% overall and in 15.7% of self-reported non vaccinated subjects. Among Canadian-born, non-vaccinated individuals, the positive test rate increased progressively from 1.2% (95% CI: 0-6.3) in 20-24 year olds to 16.4% (95% CI: 9.5-23.3) in 35-39 year olds. Antibody prevalence was higher among Canadian-born non-immunized 20-29 year olds who reported travel to developing countries (33.3%, 95% CI: 11.6-55.1) than in non-travellers (2.5%, 95% CI: 0.7-6.2). CONCLUSIONS: Mail-based population surveys of infection markers in oral fluid are feasible provided an appropriate sampling frame is used. This survey revealed a high anti-HAV antibody prevalence in young Canadian adults, increasing with age and travel to developing countries. PMID- 17278677 TI - Addressing the non-medical determinants of health: a survey of Canada's health regions. AB - BACKGROUND: The Canadian health system is undergoing reform. Over the past decade a prominent trend has been creation of health regions. This structural shift is concurrent with a greater emphasis on population health and the broad determinants of health. In parallel, there is a movement toward more intersectoral collaboration (i.e., collaboration between diverse segments of the health system, and between the health system and other sectors of society). The purpose of this exploratory study is to determine the self-reported level of internal action (within regional health authorities) and intersectoral collaboration around 10 determinants of health by regional health authorities across Canada. METHODS: From September 2003 to February 2004, we undertook a survey of regional health authorities in Canadian provinces (N = 69). Using SPSS 12.0, we generated frequencies for the self-reported level of internal and intersectoral action for each determinant. Other analyses were done to compare rural/suburban and urban regions, and to compare Western, Central and Eastern Canada. RESULTS: Of the 10 determinants of health surveyed, child development and personal health practices were self-reported by the majority of health regions to receive greatest attention, both internally and through intersectoral activities. Culture, gender and employment/working conditions received least attention in most regions. CONCLUSION: The exploratory survey results give us the first Canadian snapshot of health regions' activities in relation to the broad range of non-medical determinants of health. They provide a starting data set for baselining future progress, and for beginning deeper analyses of specific areas of action and intersectoral collaboration. PMID- 17278678 TI - Factors associated with condom use among Aboriginal people: a systematic review. AB - OBJECTIVES: To review evidence on factors associated with condom use among Aboriginal people and the methodological quality of studies assessing these factors. METHODS: A systematic review of published and unpublished literature was undertaken. Searches of databases and indexes were performed and authors were contacted directly. Studies reporting on associations between any independent variables and a condom use outcome were included. Data on the quality of each study was extracted, and the strength of evidence for associations between risk factors and condom use outcomes was assessed by counting the number of studies and sample size of each study. RESULTS: Searches yielded 17 analyses on 10 independent samples that met the inclusion criteria. Most studies were cross sectional and utilized small non-representative samples. Some evidence for a negative association between condom use and having a steady partner emerged; and a negative association between White male/Alaska Native female sex partner pairs was found. Evidence was insufficient to judge associations between other risk factors and condom use. CONCLUSIONS: The quality and quantity of evidence regarding the predictors of condom use in Aboriginal populations is limited. A concerted effort in primary research on facilitators of and barriers to condom use which are specific to and appropriate for Aboriginal people is needed to inform effective condom promotion interventions for Aboriginal communities. PMID- 17278679 TI - The relationship between diabetes and tuberculosis in Saskatchewan: comparison of registered Indians and other Saskatchewan people. AB - BACKGROUND: Saskatchewan Aboriginal people are experiencing epidemics of both type 2 diabetes (T2DM) and tuberculosis (TB). The purpose of this study was to determine if a relationship exists between diabetes and TB in Saskatchewan and to establish whether there is a difference in the degree of any association between Aboriginal and non-Aboriginal people. METHODS: Utilizing Saskatchewan Health databases, TB incidence (cases identified from 1986-2001) was compared between four subpopulations identified from 1991-1995: Registered Indians (RI) with and without diabetes, and other Saskatchewan people (OSKP) with and without diabetes. RESULTS: Diabetic women aged 20-59 years had higher average annual incidence rates of TB than non-diabetic women, but within-population rate ratios of TB in diabetic versus non-diabetic women were only significant in those aged 50-59 (2.7 [CI 1.28, 5.72] in RI and 3.9 [CI 1.58, 9.67] in OSKP). No other within population diabetic subgroup had significantly higher rates of TB. The only male diabetic group that had a higher rate of TB were RI plus OSKP men aged 50-59 years. Overall, diabetes preceded TB in 87/111 individuals with both diseases (p < 0.0001). CONCLUSIONS: Our results suggest that T2DM is a predictor for TB in Saskatchewan women aged 20-59 but particularly in RI and OSKP women aged 50-59 years. This has implications for TB screening and prevention initiatives. PMID- 17278680 TI - The changing age distribution of prostate cancer in Canada. AB - BACKGROUND: Prostate cancer incidence rates are still increasing steadily; mortality rates are levelling, possibly decreasing; and hospitalization rates for many diagnoses are decreasing. Our objective is to examine changes in age distributions of prostate cancer during these times of change. METHODS: Prostate cancer cases were derived from the Canadian Cancer Registry, prostate cancer deaths from Vital Statistics, hospitalizations from the Hospital Morbidity File. Age-standardized rates were calculated based on the 1991 Canadian population. A prevalence correction for incidence rates was calculated. RESULTS: Age-specific incidence rates increased until 1995 for all ages, but a superimposed peak (1991 94) was greatest between ages 60-79. After 1995, increases in incidence continued for the under-70 age groups. Prevalence correction indicated the greatest underestimation of incidence rates for the oldest ages, but was less in Canada than in the United States. Mortality rates increased until 1994, then levelled and slowly decreased; age-specific mortality rates showed the greatest increase for the oldest ages but the earliest downturn for younger age groups. While hospitalizations dropped drastically after 1991, this drop was confined to elderly men (70+). CONCLUSIONS: Dramatic changes in age distributions of prostate cancer incidence, mortality and hospitalizations altered age profiles of men with prostate cancer. This illustrated the changing nature of prostate cancer as a public health issue and has important implications for health care provision, e.g., the increased numbers of younger new patients have different needs from the increasing numbers of elderly long-term patients who now spend less time in hospital. PMID- 17278681 TI - The Manitoba Healthy Baby Prenatal Benefit Program: who is participating? AB - BACKGROUND: Programs offering income supplements for lower-income pregnant women have been introduced in order to reduce the incidence of poor perinatal outcomes. This study used a population-based approach to examine the characteristics of mothers who received the Healthy Baby Prenatal Benefit in Manitoba. METHODS: All women giving birth between August 2001 and April 2003 (n = 22,643) were studied using de-identified linked administrative data. Multivariate logistic regression was used to determine factors that predicted receipt of the benefit, adjusting for potential confounding effects. Separate regressions were run for all mothers, and for a group of mothers eligible to receive the benefit (N = 1962). RESULTS: Almost 29% of mothers giving birth during the study period received the prenatal benefit. Mothers were more likely to receive the benefit if they: lived outside of Winnipeg; received income assistance during pregnancy; were younger at their first birth; were unmarried; made prenatal physician visits; experienced maternal depression; were having a first birth; and lived in the lowest income areas. Despite all being eligible, only 67% of non-Winnipeg and 80% of Winnipeg women receiving income assistance received the benefit. Factors related to benefit receipt for those eligible were: living in Winnipeg; making prenatal visits; not being a young teen at current birth; and experiencing a first birth. CONCLUSION: It is important to look not only at the characteristics of benefit recipients but also at those not receiving the benefit, in order to develop strategies to reach those who may most need and benefit from the program. PMID- 17278682 TI - Determining physical activity patterns of suburban British Columbia residents. AB - BACKGROUND: Physical activity is well recognized for its role in disease prevention. Public health surveillance and action is warranted to combat the escalating economic and human costs associated with physical inactivity. METHODS: This study examined the proportion of the population who were physically active at intensities, durations and frequencies specified as the minimum to accrue health benefit as per Canada's Physical Activity Guidelines. Data were collected from 769 suburban residents via a telephone survey, and analyzed using three methods: Individual Assessment (IA) where individuals met the required frequency, intensity and duration through a combination of activities; Categorical Assessment (CA) where individuals met the required frequency, intensity and duration in one or more categories leading to duplicated head-counts; and, Time based Assessment (TA) where individuals met the required time per week (recommended frequency x duration) in a category through some combination of activity. Z-scores were used to test the null hypothesis that the proportion of people meeting the criteria in more than one category was zero. RESULTS: The number of people meeting the guidelines in more than one category (CA) is significantly different (p < 0.01) from zero for adults and the combined population, but not for children. Enough people are meeting the guidelines in more than one category to significantly influence the percentage calculated if one is not careful to avoid counting duplicates. Furthermore, significant differences were found between IA and TA for children, adults and the combined population with the time-based assessment significantly over-predicting the IA results. INTERPRETATION: While 75% of the respondents reported they had been physically active during the previous week, only 39% of respondents reported enough physical activity to meet the guidelines for health benefits. This number varies widely depending on the method of classification. Canadians should be reminded of the physical activity guidelines by their health care providers to insure that those who are active are active frequently enough to accrue health benefit. PMID- 17278683 TI - Pseudomonas aeruginosa necrotizing chondritis complicating high helical ear piercing case report: clinical and public health perspectives. AB - BACKGROUND: Auricular or high helical ear piercing is an increasingly widespread fashion trend that is associated with an increased risk of potentially serious post-piercing complications such as auricular perichondritis. CASE REPORT: An 11 year-old girl developed severe auricular perichondritis following piercing of the upper helical cartilage of her ear at a hairdressing salon. Four days post piercing, she returned to the same salon for a haircut during which the pierced site was manipulated. She presented to her family physician and was treated unsuccessfully with oral cephalexin. She was then referred to an infectious diseases consultant and received antipseudomonal intravenous antibiotics with subsequent resolution. She also required debridement and removal of necrotic cartilage. Public health investigation evaluated potential sources of infection including the piercing gun, disinfectant solutions, and hair cutting spray water bottles. Final culture results of the ear helical aspirate grew Pseudomonas aeruginosa. Pseudomonas aeruginosa was also cultured from one of the water bottles used to wet her hair during the haircut. DISCUSSION: Although the pseudomonal strains from the water bottle were different than the infecting one, this contamination presents a potential source of wound infection. Damage to the helical cartilage caused by the piercing gun may also have contributed to this infection. Initial empiric antibiotic therapy for these kinds of infection must include anti-pseudomonal coverage. Auricular or high helical ear piercing using a piercing gun is not recommended. PMID- 17278685 TI - [70 years ago]. PMID- 17278684 TI - Get me a neurosurgeon, stat! PMID- 17278686 TI - [Comment from a devoted reader]. PMID- 17278687 TI - [ENT-pediatrics on the pages of the journal]. PMID- 17278688 TI - [My teacher]. PMID- 17278689 TI - [Vestnik Otorinolaringologii in my life]. PMID- 17278690 TI - [Vestnik Otorhinolaringologii--reflections on the occasion of the journal anniversary]. PMID- 17278692 TI - [B.S. Preobrazhensky's school and its contribution to development of present-day otorhinolaryngology]. PMID- 17278691 TI - [How academician V.I. Voyachek taught us to catch "a hare"]. PMID- 17278693 TI - [Occupational ENT diseases: the past, present and future]. PMID- 17278694 TI - [Establishment of ENT allergology on the pages of Vestnik Otorinolaringologii]. PMID- 17278695 TI - [Vestibular problem: an analytical review of publications for 70 years]. PMID- 17278696 TI - [Endoscopic endonasal microsurgery in otorhinolaryngological practice]. PMID- 17278697 TI - [The problem of laryngeal cancer on the pages of Vestnik Otorinolaringologii]. PMID- 17278698 TI - [Current potentialities of laser radiation in otorhinolaryngological practice]. PMID- 17278699 TI - [Current status of surgical rehabilitation of patients with inflammation of the middle ear]. PMID- 17278700 TI - [Vestnik Otorinolaringologii--new prospects (communicative diseases: experimental and clinical approaches)]. PMID- 17278701 TI - Food restriction induced thyroid changes and their reversal after refeeding in female rats and their pups. AB - In the present study, two groups of pregnant female rats were submitted to food restriction (24 h fast versus 24 h diet intake) from the 14th day of pregnancy until either the 14th day (group B) or the 4th day after parturition (group C). All pups and their mothers were sacrificed on day 14 after delivery. The body weight of the 14-day-old pups (group B) was 46% less than the controls (group A). Free thyroxine and free triiodothyronine levels in the plasma were reduced by 44 and 16% in pups and by 20 and 36% in their mothers, respectively. These reductions were correlated with a decrease in thyroid iodine content of the pups (-50%) and their mothers (-24%). Radioiodine uptake (131I) by the thyroid gland of pups was significantly increased by 27%. Plasma TSH levels were decreased by 38% in pups and by 44% in dams. Morphological changes in thyroid glands were observed in energy restricted dams and in their pups. Some of follicles in pups were empty. Moroever in dams, we noted the presence of peripheral resorbed vacuoles, sign of thyroid hyperactivity. After a refeeding (group C) period of ten days, total recovery occurred in plasma thyroid hormone levels (FT4 and FT3) and in thyroid iodine contents of pups in spite of a partial recovery of body weights and plasma TSH levels. In dams, a partial recovery occurred in plasma thyroid hormone levels in spite of total recovery in thyroid iodine contents, while plasma TSH levels exceeded control values. A significant amelioration in thyroid histological aspects was observed in pups and their dams. PMID- 17278702 TI - Investigation of protective effects of selenium and vitamin E against DNA oxidation, membrane damage and alteration of COMT metabolism in smoke-exposed male mice (Mus musculus, Balb/c). AB - In our study, the protective effects of vitamin E and Se (selenium) against cigarette smoke hazards on second-hand smoker (passive smoker) male mice (Balb/c) were investigated. Serum MDA levels in the smoke-exposed mice were found higher than serum MDA levels of control mice and Se- and vitamin E-treated mice. But, the MDA levels of smoke-exposed plus Se- and vitamin E-treated mice were found lower than MDA levels of smoke-exposed mice at the end of the three and five months. According to these results, application of vitamin E and Se, when given to smoke-exposed mice together, had an additive protective effect against cigarette smoke hazards (p < 0.05). Vitamin E also had protective effect on formation of 8-OHdG in smoke-exposed mice. The serum 8-OHdG amounts of smoke exposed plus vitamin E-treated mice were found low, but the serum 8-OHdG amounts of smoke-exposed mice were found high. Also 8-OHdG levels in the serum of the smoke-exposed mice were increased which occurs as a result of DNA oxidation (p < 0.05). At the end of the three and five months, COMT (catechol-o-methyl transferase) activity of smoke-exposed mice livers were increased but, vitamin E and/or Se showed a significant protective effect on changing of COMT activity only at the end of the 5 months. Our results showed that MDA levels and 8-OHdG amounts were increased in the serum of smoke-exposed mice. On the other hand, vitamin E and Se had an additive protective effect against increasing MDA level. Also vitamin E had a protective effect against formation of 8-OHdG amounts and COMT activity alterations. PMID- 17278704 TI - Neurotoxic and general effects of combined subchronic exposure of rats to insecticides and heavy metals. AB - Three different insecticides: dimethoate, cypermethrin and amitraz were given, alone or combined with the heavy metals Pb, Hg and Cd, to male Wistar rats per os for 12 weeks from their 4th week of life. After the treatment period, the left hemisphere of the rats was exposed in urethane anaesthesia, and spontaneous and evoked cortical activity was recorded from the primary sensory areas. The effects of dimethoate on the spontaneous activity, and of dimethoate and amitraz on the evoked responses, were increased by the metal combination treatment, whereby the metals alone had no effect on the spontaneous and mild effect on the evoked activity. Finally, the animals were dissected, organ weights measured, and relative organ weights calculated. The weight gain of all treated groups was significantly retarded compared to the control. Several organ weights were also significantly reduced, mainly in groups receiving insecticide plus metal treatment. The toxic interactions observed in this work indicate that combined human exposure to environmental pesticide residues and heavy metals may have unexpectedly severe effects. PMID- 17278703 TI - Effects of citrus flavonoids on redox homeostasis of toxin-injured liver in rat. AB - In order to evaluate the effect of diosmin-hesperidin containing drug on redox balance and Cu, Zn, Fe and Mn concentrations of toxin-injured liver, Wistar albino rats were subjected to thioacetamide administration (500 mg TAA/l in their drinking water) with and without drug (425 mg/kg body weight/day). Animals were treated for 30 days. No significant change in the concentration of Zn, Cu, Mn and Fe in the liver was measured in TAA-treated animals compared to control. Diosmin hesperidin mixture treatment increased levels of Fe and Zn and decreased concentration of Cu of the liver in TAA-treated animals. These alterations were not significant. Decrease of both the total scavenger capacity (TSC) and the activity of superoxide dismutase (SOD) in liver homogenates were observed in TAA treated rats. The diosmin-hesperidin-supplemented diet also significantly decreased the TSC and activity of SOD in liver of both the control and toxin treated animals. On the basis of results it seems that high dosage of the diosmin hesperidin mixture induces slight changes in the Cu, Zn, Mn and Fe content of the liver, however it may decrease the scavenger capacity and the activity of SOD when applied either alone or together with thioacetamide. PMID- 17278705 TI - Immunotoxicological investigation of subacute combined exposure with low doses of Pb, Hg and Cd in rats. AB - Detectable interactions between NOEL (No Observed Effect Level) doses of Pb, Hg and Cd in general toxicological, hematological, and immune function parameters were investigated. The metals (Pb-acetate, 20 mg/kg; HgCl2, 0.40 mg/kg; CdCl2, 1.61 mg/kg) were combined. First, the rats received the combination Pb + Hg + Cd for 4 weeks per os. Significant difference vs. control was found only in the weight of lung and popliteal lymph node (PLN). The Pb + Hg and Pb + Cd combinations significantly decreased the PLN to 100 g body weight and PLN to brain weight ratio, and Pb+Hg also decreased the relative adrenal weight. After 12 weeks treatment with the same doses, effects on the thymus, kidney, and adrenal weights in the Pb + Hg, and thymus weight in the Pb + Cd, combination were seen. Pb + Cd also affected the white and red blood cell count and hematocrit. Combined with Hg or Cd, NOEL dose Pb showed toxicity, indicating that exposure limits may be inefficient in combined exposure situations. PMID- 17278706 TI - Importance of spontaneous micronucleated erythrocytes in bottlenose dolphin (Tursiops truncatus) to marine toxicology studies. AB - The objective of the work was to characterize the presence of spontaneous micronucleated erythrocytes (MNES) from peripheral blood of bottlenose dolphins (Tursiops truncatus) to evaluate the possibility to use this species as potential bioindicator of genotoxic compounds. Forty-eight blood samples from 12 bottlenose dolphins were obtain from three Mexican dolphinariums, and from 10 dolphins was possible to obtain more than one sample at different sampling times. Smears were processed and observed with an epifluorescence microscope. The average of MNES and polychromatic erythrocytes (PCE) from the 48 samples was 24.3 +/- 6.1 MNES/10,000 total erythrocytes (TE), and 9.1 +/- 5.5 PCE/1,000 TE. MNES and PCE number did not show differences between gender and age. No variations in the MNES values of the bottlenose dolphins that were sampled more than one occasion were found. Comparisons among dolphinariums revealed differences in MNES frequency, with the highest significant frequency observed in dolphins from dolphinarium "A" (26.0 +/- 5.9 MNES/10,000 TE) than dolphinarium "B" (19.5 +/- 3.1 MNES/10,000 TE) (p < 0.05) and dolphinarium "C" (18.6 +/- 3.5 MNES/10,000 TE) (p < 0.007). The presence of MNES and PCE in the bottlenose dolphin may provide a useful marine mammal model to detect DNA damage by means of micronuclei test in peripheral blood erythrocytes to evaluate genotoxicity and cytotoxicity expositions. PMID- 17278707 TI - The concentrations of antioxidant compounds in the hepatopancreas, the gills and muscle of some freshwater crayfish species. AB - We examined the concentrations of vitamin E (vit E), sulphydryl groups (-SH), total protein and protein electrophoretic profiles in the hepatopancreas, the gills and muscle of three freshwater crayfish species: Noble crayfish (Astacus astacus), stone crayfish (Austropotamobius torrentium) and spiny cheek crayfish (Orconectes limosus). Vit E concentration in the hepatopancreas of O. limosus was lower compared to A. astacus, while in the gills of O. limosus it was lower compared to both A. astacus and A. torrentium. The concentration of -SH groups was lower in the hepatopancreas of A. astacus compared to A. torrentium and O. limosus. In the gills of A. astacus and A. torrentium the concentration of -SH groups was higher compared to O. limosus. Protein concentration was higher in the hepatopancreas of A. torrentium compared to A. astacus and O. limosus. A lower protein concentration in muscle of A. torrentium was found compared to O. limosus and A. astacus. Electrophoretic analysis of proteins indicated species and tissue specifities between investigated crayfish species. Our results represent the first study of its kind and provide the basis for future studies that will consider our reported parameters as potential biomarkers for biomonitoring of basic environmental conditions and some anthropogenic impacts. PMID- 17278708 TI - Amplified fragment length polymorphism (AFLP) is useful for finding markers associated with QTL for architectural trait in Hedysarum coronarium L. AB - Amplified fragment length polymorphism (AFLP) has been proposed as a valuable tool for finding molecular markers linked to QTL controlling architectural trait. Segregation of polymorphic AFLP fragments was followed in F2 offsprings Hedysarum coronarium derived from two native wild accesions crossing: Jebel Zit x El Haouaria, which had previously characterised by morphological and AFLP markers. A comparison of profiles from the morphologically contrasted parental individuals and F2 offspring has been assessed using five AFLP primer combinations. These generated 178 bands revealed by silver-stained denaturing polyacrylamide gels, of which 150 were polymorphic. Several AFLP markers appeared to be implied in the orthotropic form that can assist the selection and improve Hedysarum forage crop. PMID- 17278710 TI - The molecular biology and immunology of glioblastoma multiforme (GBM) with the presentation of an immunotherapy protocol for a clinical trial. AB - After a short explanatory Introduction, an immunotherapy protocol is presented for glioblastoma multiforme (GBM). GBM is considered to be an incurable tumor; tumor-free survival over 2 to 3 years is so rare that when it happens the original diagnosis is questioned. It is known that the type of the genetic mutation that a given GBM tumor harbors strongly influences the length of survival. However, most patients with GBM are receiving treatment without the preparation of a microarray gene map of their tumors. It is possible that the reason for a rare and exceptional long survival was not the treatment that the patient received, but the type of gene mutations that the tumor was exposed to. It is recognized that any therapeutic approach should ideally be evaluated against the background of all prognostic factors of each individual case, prominent among them the microarray gene map of the tumor. In practice, this is not easily achieved, while the patient is in need of, and is expecting, prompt therapy. Insurance companies do not reimburse the patient, or the clinical investigators, or their institutions for investigational diagnostic tests, or such treatment modalities. A temporary compromise is possible. The emergence of empirically administered treatment modalities with extraordinary efficacy has occasionally been recorded in the history of medical oncology. In some of these rare clinical trials, the control groups were discontinued (to the dismay of the statisticians), and the control patients were enrolled in the treatment groups so to escape doom and share the benefit of the unfolding high remission inductions experienced in the treatment group. Chemo-radiotherapy of Hodgkin's disease and cisplatin therapy of certain testicular carcinomas provided the first eclat examples. More recently, the rapidly approved and marketed imitanib mesylate for Ph-chromosome-positive chronic myelogenous leukemia and the anti-HER2/neu monoclonal antibody trastuzumab, and the not yet marketed double tyrosine kinase (ErbB1/2) inhibitor lapatinib (Tykerb, GlaxoSmithKline) for a subgroup of breast carcinoma patients excelled. Thus, a clinical trial for GBM, but without precise pre-identification of all its prognostic factors, however with a great deal of evidence-based empirical expectations of benefits, for patients with rapid advarcement toward a fatal outcome, implying an element of urgency, appears to be justified. PMID- 17278709 TI - Induction of programmed cell death in aging Prorocentrum donghaiense cells as was evidenced preliminarily by the identification of associated transcripts. AB - Prorocentrum donghaiense caused large-scale red tides off Chinese coast in recent years. Expressed sequence tag (EST) analysis was carried out for this dinoflagellate in order to identify the genes involved in its proliferation and death. A cDNA library was constructed for P. donghaiense at late exponential growth phase, and 308 groups of EST were generated, which include 36 contigs and 272 singletons. Among 22 groups showed homologies with known genes, 2 matched significantly with caspase and proliferating cell nuclear antigen. Caspase and proliferating cell nuclear antigen are 2 key proteins involved in programmed cell death. Their identification evidenced preliminarily the induction of PCD in aging P. donghaiense. The identified included also calmodulin and protein phosphatase, two proteins involved in diverse cell processes including PCD by binding to or modifying others. PMID- 17278711 TI - Staphylococci induce the production of melanoma differentiation-associated protein-7/IL-24. AB - Mda-7 or IL-24, a novel member of the IL-10 cytokine family has growth inhibitory effect on several human cancers including melanoma via selective apoptosis. Expression of IL-24 could be induced in human PBMC by treatment with phytohaemagglutinin, lypopolisaccharide, IL-4 or influenza A virus infection. MATERIALS AND METHODS: Human PBMC were stimulated with staphylococcal strains originating from clinical specimens, and the appearance of IL-24 at the level of transcription and translation was followed by RT-nested PCR and Western blot assays. RESULTS: All staphylococcal strains induced IL-24 mRNA. Staphylococci, pathogenic or not, did induce the production of IL-24 in PBMC, but there was a difference between the different staphylococcal strains in their effect on the production of the IL-24 protein. CONCLUSIONS: The pathogenic S. aureus or bacteria belonging to the normal flora of the skin (S. epidermidis and S. saprophyticus) as factors stimulating the production of the Mda-7 protein may be a crucial lead in the investigation of different skin lesions. PMID- 17278712 TI - Pathogenesis of Epstein-Barr virus (EBV)-carrying lymphomas. AB - The EBV carrier state is almost general in men. The virus induces B lymphocyte proliferation in vitro, but this is counteracted in vivo by the immune response. Therefore, EBV-induced malignancies occur only when the immune response is impaired, e.g. in transplant recipients. The versatility of the viral gene expression strategy secures the consistent maintainance of the virus in healthy individuals. The viral proteins required for transformation render the cell immunogenic. Expression of the transforming genes leads to rejection, but these genes are not required for the maintenance of the viral genome. EBV is an important contributor for malignant transformation, even when it does not directly induce cell proliferation. Several mechanisms have been unravelled in EBV-associated tumors whereby the virus may modify the cellular phenotype and may influence the interaction of tumor cells with their microenvironment. The virus carrier state can lead to the evasion of apoptosis and can intensify the response to growth promoting signals, too. PMID- 17278713 TI - Efficacy of recombinant herpes simplex virus 1 glycoprotein D candidate vaccines in mice. AB - To compare the immunogenity of the herpes simplex virus 1 (HSV-1/HHV-1) recombinant glycoprotein D (gD1), as a potential protective vaccine, Balb/c mice were immunized with either gD1/313 (the ectodomain of the gD1 fusion protein consisting of 313 amino acid residues), or the plasmid pcDNA3.1-gD (coding for a full length gD1 protein, FLgD1). A live attenuated HSV-1 (deleted in the gE gene), and a HSV-1 (strain HSZP)-infected cell extract served as positive controls, and three non-structural recombinant HSV-1 fusion proteins (ICP27, UL9/OBP and thymidine kinase--TK) were used as presumed non-protective (negative) controls. Protection tests showed that the LD50 value of the challenging infectious virus increased 90-fold in mice immunized with ICP27, but remained unchanged in other control mice immunized with TK and OBP polypeptides. A significant protection (the LD50 value of challenging virus increased 800-fold) was noted following immunization with gD1/313, while immunization with the gE-del virus and/or the gD1 DNA vaccine resulted in a more than 4,000-fold increase of the challenging virus dose killing 50% of the animals. Using ELISA, elevated antibody titers were detected following immunizations with gD1/313, gE-del virus, and/or HSV-1-infected-cell extract. In addition, all of the three non-structural proteins elicited a good humoral response (with titres ranging from 1:16,000 to 1:128,000). The lowest IgG response (1:8,000) was noted after immunization with the gD1 DNA vaccine. Peripheral blood leukocytes (PBLs) as well as splenocytes from mice immunized with gD1/313, gE-del virus, and gD1-plasmid responded in lymphocyte transformation test (LTT) to the presence of purified gD1/313 antigen. For PBLs, the most significant stimulation of thymidine incorporation was registered at a gD1/313 concentration of 5 microg/100 microl, while the splenocytes from DNA vaccine-immunized mice responded already at a concentration of 1 microg/100 microl. PMID- 17278714 TI - Prevalence of Chlamydia trachomatis and oncogenic human papillomavirus types in cytologic atypia of the uterine cervix. AB - A history of having substantial Chlamydia trachomatis exposure as detected by serum antibodies is a cofactor of human papillomavirus (HPV) mediated cervical carcinogenesis. In this study, we examined the concurrent C. trachomatis infections in cytologic atypia of the uterine cervix in order to evaluate the impact of C. trachomatis infection in patients with high risk for cervical intraepithelial neoplasia. Cervical scrapes form 707 patients were subjected to PCR amplification with primer sets for HPV and C. trachomatis. Based on negative beta-globin results, 10 specimens were not eligible for further analysis. Oncogenic HPV types were detected in 278 specimens (39.8%). C. trachomatis was found only in six specimens (0.9%). In conclusion, concurrent C. trachomatis infection was uncommon and hence it was an improbable risk factor in cytologic atypia. PMID- 17278715 TI - Detection of Mycoplasma bovis with an improved pcr assay. AB - A Mycoplasma bovis species-specific PCR assay has been developed with improvement of a previously described method (Ghadersohi et al., 1997). This test and its semi-nested version (Hayman and Hirst, 2003) did not function at all in our hands. A new reverse primer (Mbr2) was designed using previously published sequence data. For testing specificity, DNA was extracted from the most frequently occurring mycoplasma species and bacteria of bovine origin. The new PCR detected only Mycoplasma bovis. Moreover, no cross-reaction was observed with the genetically closest relative species, M. agalactiae. The target organism could be detected in a dose as low as 150 CFU ml(-1) in broth cultures using ethidium-bromide-stained agarose gels. PMID- 17278716 TI - Differentiation of mycoplasma gallisepticum strains using molecular methods. AB - Increasing use of Mycoplasma gallisepticum (MG) live vaccines has led to a need for the differentiation of MG strains. The MG strains MK-7, MS-16, S6, FS-9 and R strains and the MG live vaccine strain F were compared by random amplification of polymorphic DNA (RAPD) in this study. Using RAPD, different patterns were found among the MG strains. In addition to this, we examined the differentiating potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) primers targeted at the crmA, crmB, crmC, gapA, mgc2 and pvpA genes encoding cytadherence-related surface proteins. These proteins may take part in the pathogenesis of MG-induced disease. Differentiation of strain F is based on the identification of restriction enzyme sites in the PCR amplicons. Using HphI enzyme, crmC PCR amplicons produced different RFLP patterns. Digestion of amplicons of gapA-specific PCR with MboI enzyme also produced distinct patterns. Differences were observed among strains R and F by digestion of mgc2 PCR amplicons with HaelIl and VspI enzymes and digestion of pvpA PCR amplicons with AccI, PvulI and ScrFI endonucleases. This method can be used for the rapid differentiation of vaccine strain from wild strains. Differentiation of MG strains is a great advantage for diagnosticians or practitioners and it is useful for epidemiological studies. PMID- 17278717 TI - Cloning and characterisation of the ahpA gene of Pasteurella multocida serogroup b:2 (strain P52): short communication. AB - Pasteurella multocida B:2 is responsible for haemorrhagic septicaemia in cattle and buffaloes, causing severe economic losses in the developing countries. In the present study, the ahpA gene of P. multocida B:2 (P52) was cloned, sequenced and compared with the previously reported ahpA gene sequence in P. multocida A:1, which is responsible for its haemolytic phenotype. E. coli DH5a cells were further transformed with recombinant plasmid carrying the ahpA gene from P. multocida B:2 (P52) but SDS-PAGE analysis failed to show the expression of haemolysin protein. Slight haemolysis was albeit observed in horse blood agar plates streaked with recombinant E. coli carrying the ahpA gene. Our study indicates that there is 99.6% similarity and 0.4% divergence between ahpA gene of P. multocida B:2 (P52) and P. multocida A: 1, while membrane topology analysis has predicted that ahpA is an inner membrane protein with two strong hydrophobic regions at the N and C terminals. The presence of significant homology in ahpA sequence in A: 1 and B:2 perhaps suggests a common mechanism of pathogenesis in different species of animals. PMID- 17278719 TI - Recent developments in canine atopic dermatitis: a review. AB - Atopic dermatitis (AD) is a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features. New results on the pathogenesis and therapeutic aspects are discussed in this review. IgE-mediated hypersensitivity may be involved in the largest subset of atopic patients, yet there is another subset for which such involvement cannot be documented. Alterations in epidermal barrier function, priming of cutaneous antigen presenting cells with IgE, intrinsic keratinocyte defects, and development of autoimmunity are also factors that contribute to the primary disease. Polymorphisms in regions of the genome that are of key importance to the inflammatory response contribute to the patient's clinical picture. Secondary infections, especially with Staphylococcus and yeast organisms, strongly modify or augment the inflammatory response, which changes over time. After the treatment of secondary infections and skin inflammation the avoidance of causal allergens would prevent relapse. Another causative therapy is the variously effective allergen-specific immunotherapy. The newest treatments for canine AD (cyclosporin A and tacrolimus) are highly effective at suppressing the allergic response and comparable to treatment with glucocorticoids. Canine AD presents a substantial diagnostic and therapeutic challenge over a patient's lifetime, and no single treatment is universally effective. PMID- 17278718 TI - The chicken pituitary-specific transcription factor PIT-1 is involved in the hypothalamic regulation of pituitary hormones. AB - Pit-1 is a pituitary-specific POU-domain DNA binding factor, which binds to and trans-activates promoters of growth hormone- (GH), prolactin- (PRL) and thyroid stimulating hormone-beta- (TSHbeta) encoding genes. Thyrotropin-releasing hormone (TRH) is located in the hypothalamus and stimulates TSH, GH and PRL release from the pituitary gland. In the present study, we successfully used the cell aggregate culture system for chicken pituitary cells to study the effect of TRH administration on the ggPit-l* (chicken Pit-1), GH and TSHbeta mRNA expression in vitro. In pituitary cell aggregates of 11-day-old male broiler chicks the ggPit-l * mRNA expression was significantly increased following TRH administration, indicating that the stimulatory effects of TRH on several pituitary hormones are mediated via its effect on the ggPit-l* gene expression. Therefore, a semiquantitative RT-PCR method was used to detect possible changes in GH and TSHbeta mRNA levels. TRH affected both the GH and TSHbeta mRNA levels. The results of this in vitro study reveal that ggPit-1 * has a role in mediating the stimulatory effects of TRH on pituitary hormones like GH and TSHbeta in the chicken pituitary. PMID- 17278720 TI - Seroprevalence of neosporosis in beef and dairy cattle breeds in Northeast Hungary. AB - In order to assess the seroprevalence of bovine neosporosis with indirect fluorescent antibody test (IFAT), blood samples were collected randomly from 1063 beef and dairy cattle belonging to 12 different breeds in Northeast Hungary. Antibodies to Neospora caninum were detected in 27 (2.5%) of the animals, kept on 19 of the 42 settlements included in this survey. Since samples were collected on 50 farms, herd prevalence amounted to 38%. The percentage of cattle with seroconversion increased with age, suggesting a postnatal source of infection. The highest rate of positivity was detected in Aberdeen Angus (3.3%) and Holstein Friesian cows (3.2%), and the lowest in Limousine (0.9%), but no breed predisposition was statistically substantiated. Neosporosis was more prevalent in dairy (3.4%) than in beef (1.9%) cattle, although the difference was not significant. Only three out of the seropositive cows, all of them Holstein Friesians, had a history of abortion. PMID- 17278721 TI - Babesia divergens becoming extinct in cattle of Northeast Hungary: new data on the past and present situation. AB - Previously unpublished data from 1958 to 1967 attest the occurrence of Babesia divergens in cattle in several endemic foci of Northeast Hungary. During that period the number of clinical cases showed fluctuation with intervals of 4-5 years and monophasic seasonality (peaking in June). In order to assess the current status of bovine babesiosis in that region, blood samples were collected from 654 cattle on 44 farms of 36 settlements in or near the endemic area during 2005, and serum levels of IgG antibodies to B. divergens were measured by indirect fluorescent antibody test (IFAT). Only 2 samples (0.3%) showed positivity. In one village clinical babesiosis was observed over the past few years. Animals brought into the endemic area during the spring developed haemoglobinuria in the summer of the same year, but those introduced during the summer or autumn showed clinical signs only after two years. Sampled animals born and raised locally had neither haemoglobinuria nor seroconversion. Reduction in the number of cases during the past decades may have been influenced by the availability of hosts (i.e. decrease of cattle breeding) and the activity of vectors associated with climate-related changes (e.g. increase of annual sunlight hours in the endemic area). This is the first report on the prevalence of antibodies to B. divergens in cattle in Hungary. PMID- 17278722 TI - Epidemiological and pathological study on the causes of abortion in sheep and goats in Hungary (1998-2005). AB - The objective of the investigations was to study the causes of abortion in sheep and goats in Hungary during a 7.5-year period. The authors investigated 246 cases of ovine and 75 cases of caprine abortions by different diagnostic methods. An infectious origin was found in 126 cases (51.2%) of ovine and 19 cases (25%) of caprine abortions. The most important cause of ovine and caprine abortions was Chlamydophila abortus infection with a prevalence of 46% and 17%, respectively. Other infections causing sheep and goat abortions were present only in 5.2% and 8% of the cases, respectively. The results obtained by different diagnostic methods are discussed. PMID- 17278723 TI - Detection of helicobacter candidatus suis by PCR in oesophagogastric ulcers of swine in Italy. AB - The aim of this study was to evaluate by PCR the presence of Helicobacter spp. in gastric mucus from the fundic region of the stomach and to investigate its role in oesophagogastric ulcers in swine bred and regularly slaughtered in Piedmont (Northern Italy). Stomachs from 595 regularly slaughtered swine were subjected to gross pathological examination in order to evaluate the presence of gastric ulcers (revealed in 75 cases, 12.6%). Histopathological examination was performed to better characterise erosions and ulcers. DNA extracted from gastric mucus collected from all the ulcer-affected and from 25 normal stomachs was submitted to PCR using Helicobacter spp. 16S rRNA gene target primers. Sixty-three percent (47/75) of the affected stomachs was positive as well as 24% (6/25) of the non affected ones. Sequence analysis from 5 positive samples showed 99% homology with Helicobacter candidatus suis 16S ribosomal RNA gene. PMID- 17278724 TI - Application of real-time RT-PCR utilising lux (light upon extension) fluorogenic primer for the rapid detection of avian influenza viruses. AB - A real-time RT-PCR assay utilising light upon extension fluorogenic primer (LUX RT-PCR) was developed for the rapid and efficient detection of avian influenza viruses (AIV). The assay detected each of the AIV isolates tested (16/16) and gave negative results with heterologous pathogens (17/17). The detection limit of the assay proved to be 10(-0.5) EID50/0.2 ml and 10(1.5) EID50/0.2 ml in allantoic fluid of virus-infected embryonated chicken eggs and in spiked chicken faeces samples, respectively. Based on its specificity, sensitivity and relative simplicity, the LUX RT-PCR assay provides a novel, rapid and cost-effective diagnostic tool for avian influenza surveillance and monitoring programs. PMID- 17278726 TI - 'Caring for patients involves keeping them from harm'. PMID- 17278725 TI - PVL-positive MRSA threatens nurses. PMID- 17278727 TI - 'Do we need to have senior nurses on NHS commissioning bodies'? PMID- 17278728 TI - What does your union do for you? PMID- 17278729 TI - Let's talk about sex. PMID- 17278730 TI - Preparing for smoking cessation ahead of the ban. AB - By summer 2007 smoking in all enclosed public places will be banned in the UK, while in October the legal minimum age to buy tobacco is to rise from 16 to 18 in England and Wales. As well as protecting against environmental tobacco smoke the government believes an additional 600,000 smokers will quit as a result of the ban. Through the NHS smokers can access support to help them quit. Nurses in all settings have an important role to play in educating and supporting smokers to quit. PMID- 17278731 TI - Cardiac monitoring. Part 2-- Recording a 12-lead ECG. PMID- 17278732 TI - Understanding cholesterol and its role in heart disease. AB - This article looks at cholesterol and its function in the body. It explores cholesterol's role in cardiovascular disease and the factors that contribute to high levels in the blood. PMID- 17278734 TI - Novel strategy of nitrogen removal from domestic wastewater using pilot Orbal oxidation ditch. AB - A pilot-scale Orbal oxidation ditch was operated for 17 months to optimize nitrogen removal from domestic wastewater of average COD to total nitrogen ratio of 2.7, with particular concern about the roles of dissolved oxygen (DO), mixed liquor suspended solids (MLSS) and return activated sludge (RAS) recycle ratio. Remarkable simultaneous nitrification and denitrification (SND) was observed and mean total nitrogen (TN) removal efficiency up to 72.1% was steadily achieved, at DO concentration in the out, middle and inner channel of 0.1, 0.4 and 0.7 mg/L, respectively, with an average MLSS of 5.5 g/L and RAS recycle ratio of 150%. Although the out channel took the major role in TN removal, the role of middle channel should never be ignored. The denitrification potential could be fully developed under low DO, high MLSS with adequate RAS ratio. The sludge settleability was amazingly improved under low DO operation mode, and some explanations were tried. In addition, a series of simplified batch tests were done to determine whether novel microorganisms could make substantial contribution to the performance of nitrogen removal. The results indicated that the SND observed in this Orbal oxidation ditch was more likely a physical phenomenon. PMID- 17278735 TI - Biosorption of cadmium(II) and lead(II) ions from aqueous solutions onto dried activated sludge. AB - The removal of heavy-metal ions from aqueous solutions by using dried activated sludge has been investigated in batch systems. Effect of solution pH, initial metal ion concentration, and temperature were determined. The results of the kinetic studies showed that the uptake processes of the two metal ions(Cd(lII) and Pb(ll)) followed the pseudo-second-order rate expression. The equilibrium data fitted very well to both the Langmuir and Freundlich adsorption models. The FT-IR analysis showed that the main mechanism of Cd(ll) and Pb(II) biosorption onto dried activated sludge was their binding with amide I group. PMID- 17278736 TI - Removal of a type of endocrine disruptors--di-n-butyl phthalate from water by ozonation. AB - Ozonation of synthetic water containing a type of endocrine disruptor--di-n-butyl phthalate (DBP) was examined. Key impact factors such as pH, temperature, ionic strength, ozone dosage and initial DBP concentration were investigated. In addition, the activities of radicals on uncatalysed and catalysed ozonation were studied. The degradation intermediate products were followed and the kinetic of the ozonation were assessed as well. Results revealed that ozonation of DBP followed two mechanisms. Firstly, the reaction rate of direct ozonation was slower at lower pH, temperature, and ionic strength. Secondly, when these factors were increased for indirect radical reaction, higher percentage of DBP was removed with the increase of the initial ozone dosage and the decrease of the initial DBP concentration. In addition, tert-butanol, humic substances and Fe(II) affected DBP ozonation through the radical pathway. It was determined that ozonation was restrained by adding tert-butanol for its radical inhibition effect. Furthermore, humic substances enhanced the reaction to some extent, but a slight negative effect would be encountered if the optimum dosage was exceeded. As a matter of fact, Mn(II) affected the ozonation by "active sites" mechanism. In the experiment, three different kinds of intermediate products were produced during ozonation, but the amount of products for each one of them decreased as pH, temperature, ionic strength and initial ozone dosage increased. A kinetic equation of the reaction between ozone and DBP was obtained. PMID- 17278738 TI - Performance of a novel vertical-flow settler: a comparative study. AB - By increasing particle concentration and G value (root-mean-square velocity gradient) to enhance flocculation, a novel vertical-flow settler was designed to increase sedimentation effectiveness, and to simultaneously improve operational stabilization. Due to the gradual decrease in upward flow-rate of raw water, a flocs blanket would form and suspend in the middle section of the settler, not at the bottom as in a conventional clarifier. Enough large flocs, resulted from flocculation or filtration, would continuously settle out of the flocs blanket, and simultaneously, the flocs in raw water or those forming above the blanket would ceaselessly enter the flocs blanket. As a result, the flocs concentration in the blanket could keep a dynamic balance. The hydrodynamic shear in the blanket was improved by flow separation, which was induced by the abrupt change in flow channel. Due to the floes blanket and improved hydrodynamic shear, flocculation would be enhanced, which was helpful for removing fine particles in raw water. A comparative study showed that the novel vertical-flow settler had a much better performance in the removal of the particles in raw water than a conventional one, when they treated kaolin suspensions of different concentrations (500, 100 and 50 mg/L, respectively) coagulated by polyaluminum chloride(PAC1) at the up-flow rates of I and 2 mm/s, respectively. PMID- 17278737 TI - Effect of humic substances on the precipitation of calcium phosphate. AB - For phosphorus (P) recovery from wastewater, the effect of humic substances (HS) on the precipitation of calcium phosphate was studied. Batch experiments of calcium phosphate precipitation were undertaken with synthetic water that contained 20 mg/L phosphate (as P) and 20 mg/L HS (as dissolved organic carbon, DOC) at a constant pH value in the range of 8.0--10.0. The concentration variations of phosphate, calcium (Ca) and HS were measured in the precipitation process; the crystalline state and compositions of the precipitates were analysed by powder X-ray diffraction (XRD) and chemical methods, respectively. It showed that at solution pH 8.0, the precipitation rate and removal efficiency of phosphate were greatly reduced by HS, but at solution pH > or =9.0, the effect of HS was very small. The Ca consumption for the precipitation of phosphate increased when HS was added; HS was also removed from solution with the precipitation of calcium phosphate. At solution pH 8.0 and HS concentrations <==3.5 mg/L, and at pH > or =9.0 and HS concentrations < or =10 mg/L, the final precipitates were proved to be hydroxyapatite (HAP) by XRD. The increases of solution pH value and initial Ca/P ratio helped reduce the influence of HS on the precipitation of phosphate. PMID- 17278739 TI - Influence of different substrates on the formation and characteristics of aerobic granules in sequencing batch reactors. AB - The effects of different substrates on the aerobic granulation process were studied using laboratory-scale sequencing batch reactors (SBRs). Four parallel granules sequencing batch reactors (GSBR): R1, R2, R3, and R4 were fed with acetate, glucose, peptone and fecula, respectively. Stable aerobic granules were successfully cultivated in R1, R2, R4, and smaller granules less than 500 microm were formed in R3. Morphology and the physic-chemical characteristics of aerobic granules fed with different carbon substrates were investigated by the four reactors operated under the same pressure. The aerobic granules in the four reactors were observed and found that peptone was the most stable one due to its good settleability even after a sludge age as short as 10 d. A strong correlation was testified between the characteristics of aerobic granules and the properties of carbon substrates. The stability of aerobic granules was affected by extracellular polymer substances (EPS) derived from microorganism growth during feast time fed with different carbon substrates, and the influence of the property of storage substance was greater than that of its quantity. Optimal carbon substrates, which are helpful in the cultivation and retention of well settling granules and in the enhancement of the overall ability of the aerobic granules reactors, were found. PMID- 17278740 TI - Al(III) speciation distribution and transformation in high concentration PACl solutions. AB - Effects of Al(III) concentration and pH on the speciation of Al(III) in polyaluminum chloride (PACl) solutions especially on the Al13 fraction were investigated. A series of PACl samples were prepared over the range of Al(III) concentration from 0.01 to 2.0 mol/L with the B (OH/Al ratio) value from 1.0 to 2.5 by forced hydrolysis of AlCl3. The samples were characterized by ferron assay, pH and 27Al NMR. It was shown that the Al(lIII) concentration had a dramatic effect on the hydrolysis processes and the species distribution of PACl was in relate to the decrease of pH. The fraction of Al species, Alb, (or A113) decreased and Al, increased with increase of total Al(III) concentration. Under the condition of AI(llI) 2.0 mol/L, B = 2.5, the pH value was 2.73 and no Al13 could be detected. During diluting and aging, the species distribution evolved. The Al13 could then be detected again and the amounts increased with time. If the diluted samples were concentrated by freeze dry at -35 degrees C or heating at 80 degrees C, the pH value and Al13 content would decrease with the increased concentration. It demonstrated that the key factor for formation of Al13 in concentrated PACl was pH value. PMID- 17278741 TI - Ultrafiltration with in-line coagulation for the removal of natural humic acid and membrane fouling mechanism. AB - Experimental and theoretical analysis were made on the natural humic acid removal and the membrane fouling of ultrafiltration (UF) with in-line coagulation. The results showed dissolved organic carbon (DOC) and UV254 removals by the UF with in-line coagulation at pH 7 were increased from 28% to 53% and 40% to 78% in comparison with direct UF treatment respectively. At the same time, the analysis of high performance liquid chromatography showed that UF with coagulation had significant improvement of removal of humic acid with molecular weights less than 6000 Da in particular. Compared to direct UF, the in-line coagulation UF also kept more constant permeate flux and very slight increase of transmembrane pressure during a filtration circle. Two typical membrane fouling models were used by inducing two coefficients Kc and Kp corresponding to cake filtration model and pore narrowing model respectively. It was found that membrane fouling by pore-narrowing effect was effectively alleviated and that by cake-filtration was much decreased by in-line coagulation. Under the condition of coagulation prior to ultrafiltration at pH 7, the cake layer formed on the membrane surface became thicker, but the membrane filtration resistance was lower than that at pH 5 with the extension of operation time. PMID- 17278743 TI - Removal effect on Mesocyclops leukarti and mutagenicity with chlorine dioxide. AB - Mesocyclops leukurti of zooplankton propagates excessively in eutrophic water body and it cannot be effectively inactivated by the conventional drinking water treatment process. In order to tackle this problem, a study of removal effect on Mesocyclops leukarti with chlorine dioxide in a waterworks was performed. The results showed that Mesocyclops leukarti could be effectively removed from water by 1.0 mg/L chlorine dioxide preoxidation combined with the conventional drinking water treatment process. Higher oxidizability and molecular state of chlorine dioxide in water is the key to the inactivation of Mesocyclops leukarti. The chlorite, disinfection by-products (DBPs) of chlorine dioxide, was stable at 0.45 mg/L, which is lower than that critical value of the USEPA. GC-MS examination showed that the quantity of organic substance in the water treated by chlorine dioxide obviously decreased. Ames test further revealed that the mutagenicity was reduced by chlorine dioxide with respect to prechlorine. The propagation of Mesocyclops leukarti can be inactivated effectively and safely by chlorine dioxide pre-oxidation. PMID- 17278742 TI - Removal of Cr from tannery sludge by bioleaching method. AB - Bioleaching of Cr(Ill) from tannery sludge using the mixture of ingenuous iron- and sulfur-oxidizing bacteria was investigated in batch flasks. Experiments involved the adaptation of indigenous iron- and sulfur-oxidizing bacteria, the pre-acidification the sludge to pH 6.0 and the addition of energy substrates. Results showed the inoculation of mixture of ingenuous iron- and sulfur-oxidizing bacteria and co-addition of Fe2+ and elemental sulfur accelerated acid production and increase of oxidation-reduction potential originating from the bio-oxidation of Fe2+ and elemental sulfur. Dissolved Cr concentration increased concomitant with pH decreased in the sludge and reached its maximum removal of 95.6%. The amelioration of the odor of bioleached sludge could be noted. However, 20.4% of N, 24.5% of P and 14.3% of organic matter were lost in the bioleaching process. The residual Cr content in the leached tannery sludge was acceptable for use in agriculture. This study had shown the feasibility of applying the bioleaching process, developed for sewage sludge, to tannery sludge with high Cr. PMID- 17278744 TI - Effect of components in activated sludge liquor on membrane fouling in a submerged membrane bioreactor. AB - By a membrane bioreactor with a settle tank in long-term operation and batch experiments, the effects of flocs, soluble microorganism products (SMPs) and metal ions in activated sludge liquor on membrane fouling were investigated. The results showed that foulants absorbed each other and formed a fouling layer as a "second membrane" influencing the permeability of the membrane. The "gel layer" caused by SMPs and "cake layer" by flocs showed great differences in morphology by analysis of scanning electron microscope and atomic force microscope. The "gel layer" was more compact and of poor permeability. When the membrane flux was 40 L/(m(2) x h), the rate of membrane fouling caused by supernatant (0.011 MPa/h) was greater than that by sludge liquor (0.0063 MPa/h). SMPs played very important roles on membrane fouling. In the bulking sludge, with SMPs increasing, the rate of membrane fouling (0.0132 MPa/h) was faster. While after flocculation of the SMPs, the rate of fouling decreased to 0.0034 MPa/h. Flocs could keep holes in their overlaps. They could alleviate membrane fouling by preventing the SMPs directly attaching on membrane surface. PMID- 17278745 TI - Characterization of products from photooxidation of toluene. AB - Photooxidation reaction of toluene in smog chamber systems was initiated by the UV radiation of toluene/CH3ONO/NOx mixtures. The products of the photooxidation reaction of toluene and its subsequent reactions were analyzed directly utilizing Fourier transform infrared spectrometer (FTIR). Detailed assignments to FTIR spectrum of gas-phase products were given. The information of some important functional groups in the products, such as, carbonyl groups (C-O), hydroxyl groups ( -OH), carboxylic acid (-COOH), C-C bonding, N-O bonding and C-H bonding (C-H), was got from this analysis. These results were compared to those analyzed by aerosol time of flight mass spectrometer (ATOFMS). It was found that there are some differences between FTIR analysis of gas-phase products and that of particle phase, for example, the products with carbonyl groups, which were connected to unsaturated chemical bonds, was relatively higher in the gas phase, while ketones, aldehydes, carboxylic acid and organonitrates were the dominant functional groups in the aerosol-phase reaction products. The possible reaction pathways of some important products in the gas phase were also discussed. PMID- 17278746 TI - Observations of nitrous acid and its relative humidity dependence in Shanghai. AB - Nitrous acid, HNO2, is an important precursor of OH radicals in the troposphere. Measurements of HNO2 and NO2, using differential optical absorption spectroscopy (DOAS), were performed in Shanghai, China for a period from October 22, 2004 to January 4, 2005. The mean (and median) hourly concentrations of HNO2 and NO2 during this period were 1.1 (0.7) ppb and 24 (21.4) ppb respectively. A correlation between HNO2/NO2 and PMI,( mass concentrations was obtained. This correlation suggests that significant heterogeneous chemical production of HNO2 may occur through NO2 reactions on aerosol surfaces. This hypothesis was further supported by detailed analysis of selected pollution episodes in this study. At the same time, the water dependence of HNO2 formation was studied by analysis of relative humidity (RH). It showed that the maximum HNO2/NO2 ratio was increased along with RH below 70% and inhibited at RH>70%. PMID- 17278747 TI - Acidity and conductivity of Pinus massoniana bark as indicators to atmospheric acid deposition in Guangdong, China. AB - Barks of Pinus massonianm collected from two polluted sites, Qujiang and Xiqiaoshan, and from the relatively clean site Dinghushan were used to evaluate the pollution indication by the determination of their acidity and conductivity. The acidity of the inner and outer barks from the polluted sites was significantly higher than those from the clean site, suggesting that the acidity of the bark occurred in concurrent with the air pollution. The significant lower pH values of the outer bark than the inner bark collected from all sites indicated that the outer bark was more sensitive than the inner bark in response to acid pollution, implying that the outer bark is more preferable when used as indication of atmospheric acid pollution. The conductivities of the inner barks differed significantly among the three sites, with higher values at the clean site. However, the significant differences were not observed among these sites. Furthermore, the pH values for the inner and outer barks were not correlated with the conductivity, which did not coincide with some other studies. PMID- 17278748 TI - Physicochemical characteristics of ambient particles settling upon leaf surfaces of urban plants in Beijing. AB - Particulate pollution is a serious health problem throughout the world, exacerbating a wide range of respiratory and vascular illnesses in urban areas. Urban plants play an important role in reducing particulate pollution. Physicochemical characteristics of ambient particles settling upon leaf surfaces of eleven roadside plants at four sites of Beijing were studies. Results showed that density of particles on the leaf surfaces greatly varied with plant species and traffic condition. Fraxinus chinensis, Sophora japonica, A ilanthus altissima, Syringa oblata and Prunus persica had larger densities of particles among the tall species. Due to resuspension of road dust, the densities of particles of Euonymus japonicus and Parthenocissus quinquefolia with low sampling height were 2-35 times to other taller tree species. For test plant species, micro-roughness of leaf surfaces and density of particles showed a close correlation. In general, the larger micro-roughness of leaf surfaces is, the larger density of particles is. Particles settling upon leaf surfaces were dominantly PM, (particulate matter less than 10 microm in aerodynamic diameter; 98.4%) and PM25 (particulate matter less than 2.5 microm in aerodynamic diameter; 64.2%) which were closely relative to human health. Constant elements of particles were C, O, K, Ca, Si, Al, Mg, Na, Fe, S, Cl and minerals with higher content were SiO2, CaCO3, CaMg(CO3)2, NaCI and 2CaSO4 x H20, SiO2. CaCO3 and CaMg(CO3)2 mainly came from resuspension of road dust. 2CaSO4 x H20 was produced by the reaction between CaCO3 derived from earth dust or industrial emission and SO2, H2SO4 or sulfate. NaCl was derived from sea salt. PMID- 17278749 TI - Free cupric ions in contaminated agricultural soils around a copper mine in eastern Nanjing City, China. AB - To determine the environmental free metal ion activity was a recent hot issue. A method to measure low-level free cupric ion activity in soil solution extracted with 0.01 mol/L KNO3 was developed by using cupric ion-selective electrode (ISE) and calibrating with Cu-buffer solution. Three copper buffers including iminodiacetic acid (IDA), ethylenediamine (EN), and glycine (Gly) were compared for calibrating the Cu-ISE curves in the range of free cupric ions (pCu2+) 7-13. The Cu-EN buffer showed the best electrode response and thus was applied as the calibration buffer. The pCu2+ of 39 contaminated agricultural soils around a copper mine was measured, ranging from 5.03 to 9.20. Most Cu in the soil solutions was found to be complexed with dissolved soil organic matters, averaging 98.1%. The proportion of free Cu2+ ions in the soil solutions decreased with the increasing of solution pH. Soluble Cu and free Cu2+ ions concentrations were analyzed by multiple linear regressions to evaluate the effects of soil properties on metal levels and speciation. The results showed that soil solution pH was the most significant factor influencing pCu2+ (with R2 value of 0.76), while not important for the soluble Cu concentration. PMID- 17278750 TI - Effects of elevated pO3 on carbon cycle between above and belowground organs of trees. AB - Translocation of carbohydrate from leaves to roots via phloem and reallocation from roots to leaves via xylem regulate the allocation of carbon (C) between above and belowground organs of trees. To quantitatively analyze effects of elevated ozone concentrations pO3 on the internal cycle of C, juvenile beech and spruce were grown in phytotrons and exposed to ambient and elevated pO3 (i.e. twice-ambient O3 levels, restricted to < 150 ppb) for two growing seasons. The translocation of C in the phloem and xylem was quantitatively studied by investigating the phloem/xylem-loading of sugars, the differentiation of stem conductive tissue and the hourly water flow through the stem. Results in the present study shown, elevated pO3 significantly decreased C translocation from shoot to roots in beech by reducing both sugar concentration in the phloem and conductive phloem area. Elevated pO3 also significantly decreased C reallocation from the roots to the shoot in beech by reducing both of sugar concentration in the xylem and transpiration rate. The adverse effects of elevated pO3 on C translocation in the phloem and xylem, however, were small in spruce. Contrasting to beech, spruce is less sensitive to elevated pO3, regarding to phloem differentiation and sugar concentrations in the phloem and xylem. PMID- 17278751 TI - Determination of respiration, gross nitrification and denitrification in soil profile using BaPS system. AB - A facility of BaPS (Barometric Process Separation) was used to determine soil respiration, gross nitrification and denitrification in a winter wheat field with depths of 0-7, 7-14 and 14-21 cm. N2O production was determined by a gas chromatograph. Crop root mass and relevant soil parameters were measured. Results showed that soil respiration and gross nitrification decreased with the increase of soil depth, while denitrification did not change significantly. In comparison with no-plowing plot, soil respiration increased significantly in plowing plot, especially in the surface soil of 0-7 cm, while gross nitrification and denitrification rates were not affected by plowing. Cropping practice in previous season was found to affect soil gross nitrification in the following wheat growing season. Higher gross nitrification rate occurred in the filed plot with preceding crop of rice compared with that of maize for all the three depths of 0 7, 7-14 and 14-21 cm. A further investigation indicated that the nitrification for all the cases accounted for about 76% of the total nitrogen transformation processes of nitrification and denitrification and the N2O production correlated with nitrification significantly, suggesting that nitrification is a key process of soil N2O production in the wheat field. In addition, the variations of soil respiration and gross nitrification were exponentially dependent on root mass (P<0.001). PMID- 17278752 TI - Polycyclic aromatic hydrocarbon in urban soil from Beijing, China. AB - Polycyclic aromatic hydrocarbons (EPA-PAHs) in the urban surface soils from Beijing were determined using gas chromatography and mass spectrometry (GC-MS). It is significantly complementary for understanding the PAHs pollution in soil of integrated Beijing city on the basis of the information known in the outskirts. The total concentration of 16 EPA-PAH was from 0.467 to 5.470 microg/g and was described by the contour map. Compound profiles presented that the 4-, 5- and 6 ring PAHs were major compositions. The correlation analysis showed that PAHs have the similar source in the most sampling sites and BaP might be considered as the indicator of PAHs. Characteristic ratios of anthracene (An)/(An+ phenanthrene (Phe)), fluoranthene (Flu)/(Flu+ pyrene (Pyr)) and benzo [a]pyrene (BaP)/benzo [g,h,i]perylene (BghiP) indicated that the PAHs pollutants probably mainly originated from the coal combustion and it was not negligible from vehicular emission. The level of PAHs in our study area was compared with other studies. PMID- 17278753 TI - Relationships between humic substance-bound mercury contents and soil properties in subtropical zone. AB - The bioavailability of humic substance-bound mercury (HS-Hg) has been established, while the distribution of HS-Hg in soils in relation to soil properties remains obscure. Path analysis and principal component analysis were employed in present study to investigate how soil factors influence the contents of HS-Hg in soils. Results showed that HS-Hg ranged from 0.0192 to 0.2051 mg/kg in soils. The two fractions existed in soils as humic acid-bound mercury (HA-Hg) > fulvic acid-bound mercury (FA-Hg) and the ratio of HA-Hg/FA-Hg was 1.61 on the average. Soil organic carbon (OC) and HS favorably determined soil HS-Hg and the two fractions. The mercury source forming HS-Hg derived from soil total mercury and HS-Hg. FA-Hg and HA-Hg served as mercury source for each other. In acidic soils, FA-Hg and HA-Hg consistently rose with the increase of OC, and generally HA-Hg increased more dramatically. Soils with lower pH and lighter texture contained more HS-Hg, particularly fraction of FA-Hg. Among all influencing factors, organic material source showed the strongest effect, followed by other soil properties and soil mercury source. PMID- 17278754 TI - Assessing availability, phytotoxicity and bioaccumulation of lead to ryegrass and millet based on 0.1 mol/L ca(NO3)2 extraction. AB - This study was conducted to assess availability, phytotoxicity and bioaccumulation of lead (Pb) to ryegrass (Lolium perenne L.) and millet (Echinochloa crusgalli) based on the 0.1 mol/L Ca(NO3), extraction. Effect of soil properties on availability, phytotoxicity and bioaccumulation of Pb to the two plants was also evaluated. Five soils with pH values varying from 3.8 to 7.3, organic carbon (OC) contents from 0.7% to 2.4%, and clay contents from 11.6% to 35.6% were selected. Soils were spiked with Pb to achieve a range of concentrations: 250, 500, 1000, 3000 and 5000 mg/kg. Pb availability in the spiked soils was estimated by extracting soil with 0.1 mol/L Ca(NO3)2. The results indicate that plants yield decreased with decreasing soil pH and increased with increasing soil clay and OC content. Negative relationship between available Pb and the relative dry matter growth (RDMG) of the two plants were significantly related. Available Pb used to assess EC20 (20% effective concentration) and EC50 (50% effective concentration) of millet was 119 and 300 mg/kg, respectively. Available Pb used to assess EC20 and ECs, of ryegrass was 63 and 157 mg/kg, respectively. Bioaccumulation, expressed as bioconcentration factors of Pb, was inversely related to soil pH, soil OC and clay content. Strong relationships were found between available lead and uptake by the two plants (i was 0.92 and 0.95 respectively). In general, 0.1 mol/L Ca(NO3)2 available Pb may be used to assess the availability, phytotoxicity and bioaccumulation of lead to the two plants tested. PMID- 17278755 TI - Genotoxicity of vegetables irrigated by industrial wastewater. AB - Wastewater effluents from textile dyeing and printing industries of Sanganer are discharged directly, without any treatment, into Amani Shah Nallah drainage. The drainage water takes the dissolved toxicants to flora and fauna, including crops and seasonal vegetables, being grown in the land adjoining the Nallah drainage. Thus mutagenic potential of vegetables irrigated by the water of Amani Shah Nallah drainage was investigated in the present study. The vegetables irrigated by ground water from Sanganer have also been analyzed to determine possible adverse effects of these wastewater effluents on aqua duct. PMID- 17278756 TI - Isolation and characterization of gasoline-degrading bacteria from gas station leaking-contaminated soils. AB - The effects of culture conditions in vitro and biosurfactant detection were studied on bacterial strains capable of degrading gasoline from contaminated soils near gas station. The main results were summarized as follows. Three bacteria (strains Q 10, Q14 and Q18) that were considered as efficiently degrading strains were isolated and identified as Pseudomonas sp., Flavobacterium sp. and Rhodococcus sp., respectively. The optimal growth conditions of three bacteria including pH, temperature and the concentration of gasoline were similar. The reduction in surface tension was observed with all the three bacteria, indicating the production of biosurfactant compounds. The value of surface tension reduced by the three strains Q10, Q14 and Q18 was 32.6 mN x m, 12.4 mNx m and 21.9 mN x m, respectively. Strain Q10 could be considered as a potential biosurfactant producer. Gasoline, diesel oil, benzene, toluene, ethylbenzene and xylene (BTEX) could easily be degraded by the three isolates. The consortium was more effective than the individual cultures in degrading added gasoline, diesel oil, and BTEX. These results indicate that these strains have great potential for in situ remediation of soils contaminated by gas station leaking. PMID- 17278757 TI - Effect of SO2 on the performance of Ag-Pd/Al2O3 for the selective catalytic reduction of NOx with C2H5OH. AB - The influence of SO2 on the performance of Ag-Pd/Al2O3 for the selective catalytic reduction (SCR) of NOx with C2H5OH was investigated experimentally. The activity test results suggest that Ag-Pd/Al203 shows a small activity loss in the presence of SO2 when using C2H5OH as a reductant. In situ DRIFTS spectra show that the activity loss originates from the formation of surface sulphate species on the Ag-Pd/Al2O3. The surface sulphate species formation inhibits the formation of nitrate, whereas hardly changes the partial oxidation of C2HsOH. Compared with the NOx reduction by C3H6 an obvious suppression of the surface sulphate species formation was observed by DRIFTS experiment when using C2H50H as a reductant. This phenomenon reveals the better catalytic performance and strong SO2 tolerance of Ag-Pd/Al2O3-C2H5OH system. PMID- 17278758 TI - Preparation and application of efficient TiO2 /ACFs photocatalyst. AB - Activated carbon fibers (ACFs) supported titanium dioxide (TiO2) photocatalyst was developed by sol-gel method. The surface morphology and microstructure of the photocatalyst were characterized with scan electron microscope(SEM), X-ray diffraction patterns and specific surface area analysis. The prepared photocatalyst is specially helpful for the removal of low molecular weight organic pollutants in wastewater. Decomposition efficiency of methylene blue solution by TiO2/ACFs catalyst reached almost 100% under 60 min reaction, while the decomposition efficiency by pure TiO2 was only 25% under 3 h reaction. The mineralization of toluene aqueous solution was measured by total organic carbon instrument, and the evolution of intermediate species was detected by gas chromatograph instrument. The results indicated that the prepared photocatalyst not only enhanced the photoactivity of TiO2, but also suppressed the emergence of intermediate species, which may be more deleterious to human. The enhancement of photocatalysis was due to increased efficiency of adsorption and desorption, which were control steps in heterogeneous photocatalysis. PMID- 17278759 TI - Genotoxicity evaluation and a primary risk assessment of organic pollutants in the drinking water sources of Nanjing, China. AB - An increasing number of industrial, agricultural, and commercial chemicals in the aquatic environment leads to various deleterious effects on organisms, which is becoming an increasingly serious problem in China. In this study, the comet assay was conducted to investigate the genotoxicity to human body caused by organic concentrates in the drinking water sources of Nanjing City from Yangtze River of China, and health and ecology risk due to expose to these organic pollutants were evaluated with the multimedia environmental assessment system (MEAS). For all the water samples, they were collected from four different locations in the drinking water sourcr samples, es of Nanjing City. The results of the comet assay showed that all the organic concentrates from the water samples could induce different levels DNA damages on human peripheral blood lymphocytes, and a statistically significant difference (p<0.01) was observed compared with the solvent control, which demonstrated the genotoxicity was in existence. According to the ambient severity (AS) of individual compound, we had sorted out the main organic pollutants in the drinking water source of the four waterworks, and the results showed that there was some potential hazard to human body for all the source water, namely the total ambient severity (TAS) of health for each water source was more than 1. However, the TAS of ecology for each water source was less than 1, which indicated that it was safe to ecology. The results of this investigation demonstrate the application of the comet assay and the MEAS in aquatic environmental monitoring studies, and the comet assay found to be fast, sensitive, and suitable for genotoxicity monitoring programs of drinking water source. PMID- 17278761 TI - Arsenic species analysis in porewaters and sediments using hydride generation atomic fluorescence spectrometry. AB - It was observed that the atomic fluorescence emission due to As(V) could has a 10% to 40% of fluorescence emission signal during the determination of As(III) in the mixture of As(III) and As(V). Besides, interferes from heavy metals such as Pb(lIl), Cu(ll) can cause severe increase of the signals as compared to the insignificant effects caused by Cd(II), Zn(ll), Mn(II) and Fe(Ill). On the basis of further studies, the masking agent of 8-hydroxyquinoline was used as an efficient agent to eliminate interference of As(V) emission and the heavy metal of Cu2+ and Pb2+ in the measurements of arsenic species. After a series standard additions and CRM researches, a sensitive and interference-free analytical procedure was developed for the speciation of arsenic in samples of porewaters and sediments in Poyang Lake, China. PMID- 17278760 TI - Removal of PCDD/Fs and PCBS from sediment by oxygen free pyrolysis. AB - Abstract: Few studies have dealt on the evaluation of volatilization and decomposition reactions of dioxins from sediment by oxygen free pyrolysis. In this study, the performance of pyrolysis on the removal of dioxins from sediment was investigated. Dioxin concentrations of the raw sediment and the solid residues after pyrolysis were analyzed at different conditions. Results showed a removal efficiency of 99.9999% for total dioxins at 800 degrees C and retention time of 30 min. All the polychlorinated dibenzo-furans (PCDFs) have been removed and were not formed in the solid residues at the retention time range of 30-90 min at 800 degrees C. Close to 100% removal of polychlorinated dibenzo-p-dioxins (PCDDs) was also achieved. Only trace PCDDs were detected in the solid yields at a retention time of 60 min. The highest removal efficiency of polychlorinated biphenyls (PCBs) was more than 99.9994% at a retention time of 30 min. During cooling period following pyrolysis, however, the concentration of total dioxins in solid residues increased 130 times as compared to that of the raw sediment under air atmosphere. This confirmed that some complex reactions do occur to form PCDD/Fs and PCBs from 800 to 400 degrees C in the presence of oxygen. Oxygen-free atmosphere therefore can prevent formation of dioxin during thermal process thus generating clean solid residues. PMID- 17278762 TI - A novel, simple and sensitive resonance scattering spectral method for the determination of chlorite in water by means of rhodamine B. AB - A new resonance scattering method was proposed for the determination of chlorite, basing on the resonance scattering effect of rhodamine dye. In HCl-sodium acetate buffer solution, chlorite oxidizes I- into I2 and the reaction of I2 and excess I results in I3- It is respectively combined with rhodamine dyes, including rhodamine B (RhB), butyl rhodamine B (b-RhB), rhodamine G (RhG) and rhodamine S (RhS), to form association complex particles, which exhibit stronger resonance scattering (RS) effect at 400 nm. The chlorite concentration of ClO2- in the range of 0.00726-0.218 microg/ml, 0.0102-0.292 microg/ml, 0.00726 0.145 microg/ml and 0.0290 0.174 microg/ml is respectively linear to the RS intensity of association complex particle systems at 400 nm for the RhB, b-RhB, RhG and RhS. The detection limits of the four systems were respectively 0.00436, 0.00652, 0.00580 and 0.01450 microg/ml ClO2-. In the four systems, the RhB system possesses good stability and high sensitivity. It has been applied to the analysis of chlorite in wastewater with satisfactory results. PMID- 17278763 TI - Phosphorus sorption capacities in a headstream landscape--the pond chain structure. AB - Abstract: Understanding phosphorus sorption phenomena in different wetland sediments is important in controlling the P output in headstream watersheds. The pond chain structure (PCS) is widespread in the headstream agricultural watersheds in the southeast of China. Phosphorus sorption characteristics were determined for pond surface sediments (0--12 cm) along a pond chain structure in Liuchahe watershed of Chaohu Lake. Results showed that P sorption capacities (expressed by P sorption index (PSI)) varied both with the landscape position of the ponds and sediment depth. From foothill ponds to riverside ponds the P sorption capacities indicated a significant gradient variability. The higher elevation ponds showed greater sorption capacities, and with the pond elevation decline, P sorption capacities gradually decreased. Some physico-chemical properties, such as pH, oxalate-extractable Fe (Fe,o), organic matter (TOC) and Mehlich I-extractable Ca, Mg of pond sediments also indicated significant gradient variability from high elevation ponds to low elevation ponds. Feox was the sediment parameters most highly positively correlated with PSI and was the key factor in controlling P sorption capacity in the pond chain structure (r=0.92, p<0.001). Long-term hydrologic and sediment inputs can affect the distribution of sediment constituents and further affect the P sorption capacity. Making the best of the spatial difference of sorption capacities of ponds in watersheds to control nonpoint source P pollutant is necessary. PMID- 17278764 TI - Impact of hydrothermal process on the nutrient ingredients of restaurant garbage. AB - In order to recover the nutrient resource from restaurant garbage, a complete trial with 2 factors on 5 levels of experiments was carried out. The temperature and heating time are the main factors influencing on hydrothermal process (HP) by which improves the degradability and digestibility of the restaurant garbage favorably to make animal feeds or fertilizer. The results showed the variation of protein, saccharide, and oil in the garbage. It showed that protein dissolved and liquefied during hydrothermal process, which made organic nitrogen in solid phase transfer to liquid phase. After heating at 180 degrees C for 60 min, organic nitrogen in liquid phase began to transform into ammonia. It also showed that hydrothermal process could promote the dextrinization, dissolution of the starch and its hydrolysis to reducing sugar, due to that starch in the restaurant garbage decreases and reducing sugar increases. When the temperature reached 140 degrees C, the reducing sugar started to decrease due to chemical reactions. The cellulose was stable at 100--180cC. The floatable oil increased markedly in the hydrothermal process. The suitable condition for de-oil was observed at 160 degrees C heating for 80 min. Furthermore, the extraction of grease from the solid phase accords with first-order reaction dynamic model. PMID- 17278765 TI - Entropy method for determination of weight of evaluating indicators in fuzzy synthetic evaluation for water quality assessment. AB - Considering the difficulty of fuzzy synthetic evaluation method in calculation of the multiple factors and ignorance of the relationship among evaluating objects, a new weight evaluation process using entropy method was introduced. This improved method for determination of weight of the evaluating indicators was applied in water quality assessment of the Three Gorges reservoir area. The results showed that this method was favorable for fuzzy synthetic evaluation when there were more than one evaluating objects. One calculation was enough for calculating every monitoring point. Compared with the original evaluation method, the method predigested the fuzzy synthetic evaluation process greatly and the evaluation results are more reasonable. PMID- 17278766 TI - Spatial and temporal relationships between precipitation and ANPP of four types of grasslands in northern China. AB - Precipitation is considered to be the primary resource limiting terrestrial biological activity in water-limited regions. Its overriding effect on the production of grassland is complex. In this paper, field data of 48 sites (including temperate meadow steppe, temperate steppe, temperate desert steppe and alpine meadow) were gathered from 31 published papers and monographs to analyze the relationship between above-ground net primary productivity (ANPP) and precipitation by the method of regression analysis. The results indicated that there was a great difference between spatial pattern and temporal pattern by which precipitation influenced grassland ANPP. Mean annual precipitation (MAP) was the main factor determining spatial distribution of grassland ANPP (r(2) = 0.61, P < 0.01); while temporally, no significant relationship was found between the variance of ANPP and inter-annual precipitation for the four types of grassland. However, after dividing annual precipitation into monthly value and taking time lag effect into account, the study found significant relationships between ANPP and precipitation. For the temperate meadow stcppe, the key variable determining inter-annual change of ANPP was last August May precipitation (r(2) 0.47, P= 0.01); for the temperate steppe, the key variable was July precipitation (r(2)= 0.36, P= 0.02); for the temperate desert steppe, the key variable was April-June precipitation (r(2)=0.51, P< 0.01); for the alpine meadow, the key variable was last September-May precipitation (r(2)= 0.29, P < 0.05). In comparison with analogous research, the study demonstrated that the key factor determining inter-annual changes of grassland ANPP was the cumulative precipitation in certain periods of that year or the previous year. PMID- 17278767 TI - Methodology to determine regional water demand for instream flow and its application in the Yellow River Basin. AB - In order to realistically reflect the difference between regional water demand for instream flow and river ecological water demand as well as to resolve the problem that water demand may be counted repeatedly, a concept of regional water demand for minimum instream flow have been developed. The concept was used in the process of determining river functions and calculating ecological water demand for a river. The Yellow River watershed was used to validate the calculation methodology for regional water demand. Calculation results indicate that there are significant differences in water demands among the different regions. The regional water demand at the downstream of the Yellow River is the largest about 14.893 X 10(9) m(3)/a. The regional water demand of upstream, Lanzhou-Hekou section is the smallest about -5.012 x 10(9) m(3)/a. The total ecological water demand of the Yellow River Basin is 23.06 X 10(9) m(3)/a, about the 39% of surface water resources of the Yellow River Basin. That means the maximum available surface water resources should not exceed 61% in the Yellow River Basin. The regional river ecological water demands at the Lower Section of the Yellow River and Longyangxia-Lanzhou Section exceed the surface water resources produced in its region and need to be supplemented from other regions through the water rational planning of watershed water resources. These results provides technical basis for rational plan of water resources of the Yellow River Basin. PMID- 17278768 TI - Computerized multichannel lung sound analysis. Development of acoustic instruments for diagnosis and management of medical conditions. PMID- 17278769 TI - Separating heart sounds from lung sounds. Accurate diagnosis of respiratory disease depends on understanding noises. PMID- 17278770 TI - Empirical mode decomposition and fractal dimension filter. A novel technique for denoising explosive lung sounds. PMID- 17278771 TI - Crackle sounds analysis by empirical mode decomposition. Nonlinear and nonstationary signal analysis for distinction of crackles in lung sounds. PMID- 17278772 TI - Modeling human respiratory impedance. Comparing the best method with the least estimation errors. PMID- 17278773 TI - Acoustical respiratory flow. A review of reliable methods for measuring air flow. PMID- 17278774 TI - Smart smooth muscle spring-dampers. Smooth muscle smart filtering helps to more efficiently protect the arterial wall. PMID- 17278775 TI - Ensemble-based RNA secondary structure characterization. PMID- 17278776 TI - Interoperability: the cure for what ails us. PMID- 17278777 TI - FDA-regulated validation in clinical and nonclinical environments. PMID- 17278778 TI - [Modern strategy of diagnostics and management of patients with rheumatoid arthritis]. PMID- 17278779 TI - [Serum concentration of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) correlates with markers of the disease activity in early rheumatoid arthritis]. AB - The aim of the study was to analyse the correlations between serum concentrations of the tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and clinical markers of the disease activity in patients with early rheumatoid arthritis. The study group consisted of 30 RA patients, untreated with disease modifying anti rheumatic drugs or corticosteroids, with disease duration less than 3 years. The analysis of serum concentrations of TIMPs was based on a quantitative sandwich ELISA. We found the positive correlations between serum TIMP-1 level and clinical markers of the disease activity such as the Ritchie articular index, erythrocyte sedimentation rate (ESR) and disease activity score (DAS) (in all cases p<0.05). Furthermore, we observed positive correlations between serum TIMP-2 concentration and ESR (p<0.01). We conclude that studied tissue inhibitors of matrix metalloproteinases might be useful clinical markers of the disease activity in early rheumatoid arthritis. PMID- 17278780 TI - [The leptin concentration in patients with primary arterial hypertension]. AB - Leptin seems to play a role in the pathogenesis of arterial hypertension by activation of the sympathetic nervous system, influencing water - electrolyte balance and vascular remodeling. It is not known whether leptin is a factor participating in the pathogenesis of primary arterial hypertension or its higher concentration in patients with arterial hypertension reflects only the presence of other factors leading to increased blood pressure. The aim of the study was to try to estimate the leptin participation in the development of the arterial hypertension, to evaluate the concentration of leptin in blood serum of patients with mild, moderate and severe arterial hypertension and to determine the relationships between the observed leptin concentration, arterial hypertension degree according to WHO criteria and body mass. The investigations were performed on 74 untreated patients aged 19-74 years (mean 47 +/- 12 years ). In this group there were 33 women aged 35-74 years (mean 51 +/- 10 years) and 41 men aged 19-73 years (mean 45 +/- 14 years). The mild arterial hypertension was observed in 24 patients, moderate hypertension in 34 patients and severe hypertension in 16. The obesity, identified when BMI was equal or higher than 30 kg/m2, was observed in 4 patients with mild hypertension, in 9 with moderate hypertension and in 6 with severe hypertension. All patients had normal renal function. The leptin concentration was determined by the radioimmunological method using the Human Leptin RIA Kit by LINCO Research, Inc. (Cat# HL-81 K). The analysis of the obtained results was performed using Statistica for Windows PL.V5.0. RESULTS: The concentration of leptin in patients with mild hypertension was 3.61 +/- 2.22 ng/ml, in patients with moderate hypertension was 12.65 +/- 8.48 and in patients with severe hypertension 33.51 +/- 28.45 ng/ml. The concentration of leptin in obese patients was 24.83 +/- 26.60 and in patients without obesity was 10.57 +/- 11.99 ng/ml. CONCLUSIONS: 1. In patients with moderate and severe hypertension the leptin serum concentration is significantly higher than mild hypertension, and in patients with severe hypertension the leptin serum concentration is significantly higher than in patients with moderate hypertension. 2. In patients suffering from arterial hypertension the leptin serum concentration is positively correlated with the body mass index. 3. The leptin serum concentration is statistically significantly higher in women with arterial hypertension as compared to the male patients with the same disease. 4. In both male and female groups of patients the leptin serum concentration is positively correlated with the arterial hypertension degree. 5. In female patients suffering from arterial hypertension the leptin serum concentration is positively correlated with the body mass and body mass index. PMID- 17278781 TI - [Plasminogenesis in blood of patients with chronic myeloproliferative syndromes]. AB - The aim of the study was the evaluation of the participation of fibrinolytic system in the pathogenesis of haemostasis disturbances on the base of the determination of plasminogenesis intensity and some other fibrinolytic parameters. The study was performed in the group of 73 patients suffering from chronic meyloproliferative syndromes aged 36-78 (means 54,0) years: in 22 with chronic myelogenous leukemia (CML), in 25 with polycythemia vera (PV), in 21 with essential thrombocythemia (ET) and in 5 patients with meylofibrosis (MF). Control group contained 30 healthy volunteers sex and age matched. In the citric plasma obtained from venous blood concentration of plasmin-alpha2 antiplasmin complexes (PAP) using immunosorbed method (ELISA), alpha-2-antiplasmin with chromogenic method, concentration of fibrinogen and fibrin/ /fibrinogen degradation products (FDP) were determined. In blood plasma of patients with chronic myeloproliferative syndromes increased concentration of PAP complexes was detected what is the evidence of high intensity of plasmin generation. PMID- 17278782 TI - [The destiny of persons with diabetes mellitus type 2 after first myocardial infarction--analysis of the cohort living in well defined environment]. AB - Ischemic heart disease (IHD) and acute myocardial infarction (AMI) present several important specificities in their clinical course. The problem how these circumstances influence the life of the persons with diabetes (DM) in longer perspective is not well elaborated. Therefore the assessment of the medical history of persons with DM after first MI was undertaken based on analysis of the following endpoints: the recurrence of MI, hospitalization due to acute heart ischemic incidents, the procedure of coronary revascularization, appearance of stroke, death due to cardiovascular causes. INVESTIGATED GROUP AND METHODS: During the years 1996-2000 69 subjects with AMI were hospitalized from the area of the local, urban hospital. The medical documentation supplemented by the patient and family home reviews and data from death registry office for the period of 2 years since the hospitalization due to first AMI was analyzed. RESULTS: In the group under study the males aged between 61 and 70 years were preponderant - 20,3%, the largest females subgroup was in the age between 71 and 80 years - 17,4%. The first AMI was the revelatory of the previously not known DM in 30,4% of cases, 21,7% subjects had the diagnosis of DM made in the last 5 years before first AMI. The symptoms of IHD were present before first AMI in 49% of subjects. 82% of them had the Q type AMI in 23% localized in inferior, in 17% in anterior and in 16% in lower-posterior wall of the heart. The frequencies of other then hyperglycaemia risk factors were: arterial hypertension - 67%, obesity and overweight respectively 38% and 26%, smoking - 32%, dyslipidemia - 28%. The risk factors were often multiple in the form of metabolic syndrome. During the 2 years of the follow-up after first AMI, 34,6% of subjects died. In 72,2% of this subgroup the mortality was due to the cardiovascular syndromes - recurrent MI, cardiac failure, stroke and "generalized atherosclerosis". The rate of hospitalization caused by acute ischemic incidents was 25%, recurrent MI - 11,5%, cardiosurgical intervention - 5,8%, stroke - 3,8%. CONCLUSIONS: The mortality level of 34,6% during 2 years after first AMI due to new cardiovascular events is the measure of the specific unfavourable prognosis for diabetic persons after first AMI. It underlines the need of the implementation in this subgroup of the intensified cardio-diabetological secondary prevention plan. PMID- 17278783 TI - [Neoplastic pericarditis--the role of different diagnostic procedures]. AB - The aim of the study was to assess the role of different diagnostic procedures in the recognition of malignant pericarditis. Consecutive medical records of the patients with pericardial effusion treated with pericardiocentesis or pericardioscopy in the period of 1982-2002 were analyzed retrospectively. Criteria of neoplastic pericarditis were: positive result of pericardial fluid cytology and/or neoplastic infiltration found in pericardial biopsy specimen. Criteria of non-neoplastic pericarditis were: negative result of pericardial fluid cytology and pericardial biopsy specimen, no neoplastic disease diagnosed at presentation and during 3-years of follow up. Malignant pericarditis was diagnosed in 47 patients (pts), nonmalignant in 51. Echocardiographic signs of cardiac tamponade were found in 80% of pts with neoplastic pericarditis and 40% of pts with non-malignant disease (p = 0.0001). Chest CT scan revealed the presence of enlarged mediastinal lymph nodes in 94% of pts with malignant pericarditis and only 11% of pts with non-malignant disease (p = 0.00001). Pericardial thickness on CT scan exceeded 8 mm in 75% of the pts with malignant pericarditis and 8% of pts with nonmalignant disease (p = 0.0003). Pericardial fluid (pf) CEA concentration was significantly higher in the patients with neoplastic pericarditis than in the pts with non-malignant process. CEA > 5 ng/ml and Cyfra 21-1>50 ng/ml were found in 43% of the pts with malignant pericarditis and none of the pts with benign pericarditis. Thus we recommend chest CT scan and pericardial fluid tumor markers (CEA and Cyfra 21-1) assessment as the procedures helpful in the recognition of malignant pericarditis. PMID- 17278784 TI - [Fenofibrate--induced myopathy in a patient with undiagnosed hypothyroidism--case report and a review of the literature]. AB - Hypothyroidism is one of the common causes of the secondary hypercholesterolemia. The prevalence of hypothyroidism in the general population is estimated to be as high as about 1.5%. Frequency of the hypothyroidism in patients with hyperlipidemia is high, and can be observed in 4.2-10% in different populations. Most commonly, there is no need to treat the hypothyroid patients with the hypolipidemic drugs. Substitution treatment with the thyroid hormones usually results in either normalization or significant decreasing of the lipid levels. Hypothyroidism with symptoms of involvement of skeletal muscles is referred as to hypothyroid myopathy in English literature, and can be present in 30-80% patients with deficiency of the thyroid hormones. Hypothyroidism is a risk factor of developing of toxic injury of muscles, what is thought to be related to hypolipidemic drug intake. We report a case of a patient with undiagnosed hypothyroidism with muscle involvement manifestation, who was treated with fenofibrate due to accidentally diagnosed hypercholesterolemia. Hypolipidemic management resulted in rapid exacerbation of previously moderate myopathy. High concentrations of muscle enzymes and moderate increasing of creatinine concentration were detected. Improvement was observed after discontinuation of fenofibrate administration, but muscle symptoms and elevation of muscle enzymes and creatinine persisted. After administration of levothyroxin, muscle weakness and laboratory abnormalities were observed no longer. After several months of follow-up we believe that treatment with fenofibrate in our patient was complicated with muscle tissue damage and exacerbated symptoms of myopathy originally related to decompensated hypothyroidism. PMID- 17278785 TI - [New possibilities of making the diagnosis of Caplan syndrome]. AB - We describe a 56-year old man with rheumatoid arthritis and pulmonary nodules detected by HRCT. Needle biopsy confirmed the diagnosis of Caplan syndrome. PMID- 17278786 TI - [Effect of cardiac rehabilitation on blood lipids]. PMID- 17278787 TI - [Age and ethanol metabolism]. PMID- 17278788 TI - [Primary and secondary prevention of sudden cardiac death]. PMID- 17278789 TI - [Physical activity and selected adipokines: adiponectin, leptin and resistin]. PMID- 17278790 TI - [Application of anti-cD154, anti-CD25 and anti-CD152 antibodies--attempt to achieve immunological tolerance]. PMID- 17278791 TI - Dehydrating of flax fiber with microwave heating for biocomposite production. AB - The feasibility of microwave dehydrating flax fiber was evaluated using a commercial domestic microwave oven at four power settings representing 200, 300, 400 and 500 Watt (W) power level. Due to the possibility of local heating and consequent fiber degradation, the changes in color of the flax fiber at different levels of temperature were also investigated. The dehydration processes at various power levels were simulated by Page model. Based on visual inspection, color analysis and scanning electron microscopy (SEM) of the fiber, it was revealed that discoloration of the fiber occurred at about 170 degrees C. At 200 and 300 W power level, after 10 minutes of dehydrating, the moisture content of the fiber reached from initial 7.9% close to 2.0 and 1.0%, respectively. For 400 W power level, the moisture content of the fiber dropped to 0. 10% in about 9.5 minutes. Major discoloration of the fiber was noticed when dehydration was proceed beyond 4.5 minutes for 500 W treatment. The Page model very well fitted the experimental data. The coefficients of determination calculated from the model and the experimental data increased with increase in applied microwave power PMID- 17278792 TI - A finite difference thermal model of a cylindrical microwave heating applicator using locally conformal overlapping grids: part II--numerical results and experimental evaluation. AB - In this paper, we present numerical results obtained from a robust, locally conformal 3-D Orthogonal Grid Finite Difference (OGFD) thermal algorithm introduced in Part I of our current investigation [Al-Rizzo et al., 2006] integrated with an Orthogonal Grid Finite-Difference Time Domain (OGFDTD) scheme [Al-Rizzo et al., 2000], which accurately models the volumetric electromagnetic (EM) power deposition pattern. A unified meshing scheme, which utilizes identical overlapping grids in Cartesian and cylindrical coordinates, is employed within the load zone in the OGFDTD and OGFD models. Local temperature profiles excited by the absorbed microwave energy were measured at seven locations within the sample as a function of heating time. In order to benchmark, or validate our model, an alternative analysis of the coupled EM and thermal simulations was performed using state-of-the-art, Finite Element Method-based Ansoft's High Frequency Structure Simulator (HFSS) and the coupled thermal/stress analysis tool ePHYSICS (http://www.ansoft.com). Additionally, we compare our numerical simulations against measured dynamic temperature profiles induced within a mineral ore sample maintained for exposure period of 28.5 minutes inside a cylindrical multimode heating furnace energized at 915 MHz with a microwave source power of 12.5 kW and accompanied with significant temperature elevation. A combination of convective and radiation thermal boundary conditions are considered at the interfaces between the cavity walls, air, and sample. There is a general agreement between simulated and measured spatial and temporal temperature profiles, which validates the proposed model. Results indicate that inevitable fluctuations in the frequency spectrum and output power of the magnetron, non-uniformity of sample packing, and heat released by uncontrolled exothermic chemical reactions have a significant effect on the comparisons between measured and computed temperature patterns. PMID- 17278793 TI - Modelling of industrial conveyorized applicators using higher order vector finite elements. AB - This paper presents a finite element time domain method for the solution of Maxwell's equations in microwave heating applicators using first and second order vector finite elements. Results are compared with experimental data and it has been shown that second order vector finite elements have many advantages over first order elements. Capitalising on the high accuracy and low computational cost attainable by higher order elements, an industrial conveyor belt system is numerically analyzed. PMID- 17278794 TI - A density-independent method for high moisture content measurement using a microstrip transmission line. AB - This paper describes a method to measure high moisture content in materials from 190% to 350% on a dry weight basis. The method uses a microstrip transmission line, on which the material under test is overlaid. A parameter calculated from the attenuation and phase shift of the microwave signal is proposed to measure the moisture content. The experiments were performed on samples of sawdust, and the results show that the method is able to determine high moisture content independent of density. The standard error of calibration for the moisture content determination was 12.4% in the moisture content range from 190% to 350%. PMID- 17278795 TI - Properties of microwave cavities for radiometric temperature measurement. AB - Cavity-type coupling structures can be used for industrial microwave radiometric temperature measurement in lossy dielectrics. The cavity properties which determine the measured radiometric signal are defined and applied, and a simple technique for measuring these properties is described. PMID- 17278796 TI - Point/counterpoint. It is important that medical physicists be involved in the development and implementation of integrated hospital information systems. PMID- 17278797 TI - Characterization of the susceptibility artifact around a prostate brachytherapy seed in MRI. AB - Magnetic distortions surrounding a typical brachytherapy seed (IMC6711, OncoSeed) within a clinical magnetic resonance imager were modeled for a number of different seed orientations with respect to the main magnetic field. From these distortion maps, simulated images were produced. The simulated images were then compared to images experimentally acquired using a spin echo technique on a Philips 1.5 T magnetic resonance imaging scanner. The modeled images were found to conform very well to those acquired experimentally, thus allowing one to establish where the seed is positioned within the complex image distortion patterns. The artifact patterns were dependent on the orientation of the seed with the main magnetic field, as well as the direction of the read encode gradient. While all imaging schemes which employ a unidirectional linear read encode trajectory should produce the artifacts modeled in this article, sequences other than spin echo may produce additional artifacts. Gradient echo and steady state free precession imaging techniques were also performed on the seed for comparison. PMID- 17278798 TI - Using fluence separation to account for energy spectra dependence in computing dosimetric a-Si EPID images for IMRT fields. AB - This study develops a method to improve the dosimetric accuracy of computed images for an amorphous silicon flat-panel imager. Radially dependent kernels derived from Monte Carlo simulations are convolved with the treatment-planning system's energy fluence. Multileaf collimator (MLC) beam hardening is accounted for by having separate kernels for open and blocked portions of MLC fields. Field size-dependent output factors are used to account for the field-size dependence of scatter within the imager. Gamma analysis was used to evaluate open and sliding window test fields and intensity modulated patient fields. For each tested field, at least 99.6% of the points had gamma < 1 with a 3%, 3-mm criteria. With a 2%, 2-mm criteria, between 81% and 100% of points had gamma < 1. Patient intensity modulated test fields had 94%-100% of the points with gamma < 1 with a 2%, 2-mm criteria for all six fields tested. This study demonstrates that including the dependencies of kernel and fluence on radius and beam hardening in the convolution improves its accuracy compared with the use of radial and beam hardening independent kernels; it also demonstrates that the resultant accuracy of the convolution method is sufficient for pretreatment, intensity modulated patient field verification. PMID- 17278799 TI - On relating the generalized equivalent uniform dose formalism to the linear quadratic model. AB - Two main approaches are commonly used in the literature for computing the equivalent uniform dose (EUD) in radiotherapy. The first approach is based on the cell-survival curve as defined in the linear-quadratic model. The second approach assumes that EUD can be computed as the generalized mean of the dose distribution with an appropriate fitting parameter. We have analyzed the connection between these two formalisms by deriving explicit formulas for the EUD which are applicable to normal distributions. From these formulas we have established an explicit connection between the two formalisms. We found that the EUD parameter has strong dependence on the parameters that characterize the distribution, namely the mean dose and the standard deviation around the mean. By computing the corresponding parameters for clinical dose distributions, which in general do not follow the normal distribution, we have shown that our results are also applicable to actual dose distributions. Our analysis suggests that caution should be used in using generalized EUD approach for reporting and analyzing dose distributions. PMID- 17278800 TI - Direct aperture deformation: an interfraction image guidance strategy. AB - A new scheme, called direct aperture deformation (DAD), for online correction of interfraction geometric uncertainties under volumetric imaging guidance is presented. Using deformable image registration, the three-dimensional geometric transformation matrix can be derived that associates the planning image set and the images acquired on the day of treatment. Rather than replanning or moving the patient, we use the deformation matrix to morph the treatment apertures as a potential online correction method. A proof-of-principle study using an intensity modulated radiation therapy plan for a prostate cancer patient was conducted. The method, procedure, and algorithm of DAD are described. The dose-volume histograms from the original plan, reoptimized plan, and rigid-body translation plan are compared with the ones from the DAD plan. The study showed the feasibility of the DAD as a general method for both target dislocation and deformation. As compared with using couch translation to move the patient, DAD is capable of correcting both target dislocation and deformations. As compared with reoptimization, online correction using the DAD scheme could be completed within a few minutes rather than tens of minutes and the speed gain would be at a very small cost of plan quality. PMID- 17278801 TI - Low magnetic moment PIN diodes for high field MRI surface coils. AB - Positive-intrinsic-negative (PIN) silicon diodes are commonly used in magnetic resonance imaging (MRI) coils to perform active or passive blocking and detuning, or to disable circuit functions. However, diode packages with large magnetic moments are known to cause image artifacts in high field MRI systems. In this study, diode packages with low magnetic moment were designed by compensating components of ferromagnetic nickel and paramagnetic tungsten with diamagnetic silver. The new diodes have an initial positive susceptibility up to fields of 1 T and a negative susceptibility from 1 to 7 T. Their magnetic moments are one to two orders of magnitude smaller than those of standard diodes; moments as small as 20 nJ/T at 7 T were achieved. PMID- 17278802 TI - Modeling granular phosphor screens by Monte Carlo methods. AB - The intrinsic phosphor properties are of significant importance for the performance of phosphor screens used in medical imaging systems. In previous analytical-theoretical and Monte Carlo studies on granular phosphor materials, values of optical properties, and light interaction cross sections were found by fitting to experimental data. These values were then employed for the assessment of phosphor screen imaging performance. However, it was found that, depending on the experimental technique and fitting methodology, the optical parameters of a specific phosphor material varied within a wide range of values, i.e., variations of light scattering with respect to light absorption coefficients were often observed for the same phosphor material. In this study, x-ray and light transport within granular phosphor materials was studied by developing a computational model using Monte Carlo methods. The model was based on the intrinsic physical characteristics of the phosphor. Input values required to feed the model can be easily obtained from tabulated data. The complex refractive index was introduced and microscopic probabilities for light interactions were produced, using Mie scattering theory. Model validation was carried out by comparing model results on x-ray and light parameters (x-ray absorption, statistical fluctuations in the x ray to light conversion process, number of emitted light photons, output light spatial distribution) with previous published experimental data on Gd2O2S: Tb phosphor material (Kodak Min-R screen). Results showed the dependence of the modulation transfer function (MTF) on phosphor grain size and material packing density. It was predicted that granular Gd2O2S: Tb screens of high packing density and small grain size may exhibit considerably better resolution and light emission properties than the conventional Gd2O2S: Tb screens, under similar conditions (x-ray incident energy, screen thickness). PMID- 17278803 TI - Dosimetric characterization of a novel intracavitary mold applicator for 192Ir high dose rate endorectal brachytherapy treatment. AB - The dosimetric properties of a novel intracavitary mold applicator for 192Ir high dose rate (HDR) endorectal cancer treatment have been investigated using Monte Carlo (MC) simulations and experimental methods. The 28 cm long applicator has a flexible structure made of silicone rubber for easy passage into cavities with deep-seated tumors. It consists of eight source catheters arranged around a central cavity for shielding insertion, and is compatible for use with an endocavitary balloon. A phase space model of the HDR source has been validated for dose calculations using the GEANT4 MC code. GAFCHROMIC EBT model film was used to measure dose distributions in water around shielded and unshielded applicators with two loading configurations, and to quantify the shielding effect of a balloon injected with an iodine solution (300 mg I/mL). The film calibration procedure was performed in water using an 192Ir HDR source. Ionization chamber measurements in a Lucite phantom show that placing a tungsten rod in the applicator attenuates the dose in the shielded region by up to 85%. Inserting the shielded applicator into a water-filled balloon pushes the neighboring tissues away from the radiation source, and the resulting geometric displacement reduces the dose by up to 53%; another 8% dose reduction can be achieved when the balloon is injected with an iodine solution. All experimental results agree with the GEANT4 calculations within measurement uncertainties. PMID- 17278804 TI - Monte Carlo modelling of a-Si EPID response: the effect of spectral variations with field size and position. AB - This study focused on predicting the electronic portal imaging device (EPID) image of intensity modulated radiation treatment (IMRT) fields in the absence of attenuation material in the beam with Monte Carlo methods. As IMRT treatments consist of a series of segments of various sizes that are not always delivered on the central axis, large spectral variations may be observed between the segments. The effect of these spectral variations on the EPID response was studied with fields of various sizes and off-axis positions. A detailed description of the EPID was implemented in a Monte Carlo model. The EPID model was validated by comparing the EPID output factors for field sizes between 1 x 1 and 26 x 26 cm2 at the isocenter. The Monte Carlo simulations agreed with the measurements to within 1.5%. The Monte Carlo model succeeded in predicting the EPID response at the center of the fields of various sizes and offsets to within 1% of the measurements. Large variations (up to 29%) of the EPID response were observed between the various offsets. The EPID response increased with field size and with field offset for most cases. The Monte Carlo model was then used to predict the image of a simple test IMRT field delivered on the beam axis and with an offset. A variation of EPID response up to 28% was found between the on- and off-axis delivery. Finally, two clinical IMRT fields were simulated and compared to the measurements. For all IMRT fields, simulations and measurements agreed within 3% 0.2 cm for 98% of the pixels. The spectral variations were quantified by extracting from the spectra at the center of the fields the total photon yield (Ytotal), the photon yield below 1 MeV (Ylow), and the percentage of photons below 1 MeV (Plow). For the studied cases, a correlation was shown between the EPID response variation and Ytotal, Ylow, and Plow. PMID- 17278805 TI - Dose and image quality for a cone-beam C-arm CT system. AB - We assess dose and image quality of a state-of-the-art angiographic C-arm system (Axiom Artis dTA, Siemens Medical Solutions, Forchheim, Germany) for three dimensional neuro-imaging at various dose levels and tube voltages and an associated measurement method. Unlike conventional CT, the beam length covers the entire phantom, hence, the concept of computed tomography dose index (CTDI) is not the metric of choice, and one can revert to conventional dosimetry methods by directly measuring the dose at various points using a small ion chamber. This method allows us to define and compute a new dose metric that is appropriate for a direct comparison with the familiar CTDIw of conventional CT. A perception study involving the CATPHAN 600 indicates that one can expect to see at least the 9 mm inset with 0.5% nominal contrast at the recommended head-scan dose (60 mGy) when using tube voltages ranging from 70 kVp to 125 kVp. When analyzing the impact of tube voltage on image quality at a fixed dose, we found that lower tube voltages gave improved low contrast detectability for small-diameter objects. The relationships between kVp, image noise, dose, and contrast perception are discussed. PMID- 17278806 TI - Important considerations for radiochromic film dosimetry with flatbed CCD scanners and EBT GAFCHROMIC film. AB - In this study, we present three significant artifacts that have the potential to negatively impact the accuracy and precision of film dosimetry measurements made using GAFCHROMIC EBT radiochromic film when read out with CCD flatbed scanners. Films were scanned using three commonly employed instruments: a Macbeth TD932 spot densitometer, an Epson Expression 1680 CCD array scanner, and a Microtek ScanMaker i900 CCD array scanner. For the two scanners we assessed the variation in optical density (OD) of GAFCHROMIC EBT film with scanning bed position, angular rotation of the film with respect to the scan line direction, and temperature inside the scanner due to repeated scanning. Scanning uniform radiochromic films demonstrated a distinct bowing effect in profiles in the direction of the CCD array with a nonuniformity of up to 17%. Profiles along a direction orthogonal to the CCD array demonstrated a 7% variation. A strong angular dependence was found in measurements made with the flatbed scanners; the effect could not be reproduced with the spot densitometer. An IMRT quality assurance film was scanned twice rotating the film 90' between the scans. For films scanned on the Epson scanner, up to 12% variation was observed in unirradiated EBT films rotated between 0 degrees and 90 degrees, which decreased to approximately 8% for EBT films irradiated to 300 cGy. Variations of up to 80% were observed for films scanned with the Microtek scanner. The scanners were found to significantly increase the film temperature with repeated scanning. Film temperature between 18 and 33 degrees C caused OD changes of approximately 7%. Considering these effects, we recommend adherence to a strict scanning protocol that includes: maintaining the orientation of films scanned on flatbed scanners, limiting scanning to the central portion of the scanner bed, and limiting the number of consecutive scans to minimize changes in OD caused by film heating. PMID- 17278808 TI - Thick, segmented CdWO4-photodiode detector for cone beam megavoltage CT: a Monte Carlo study of system design parameters. AB - Megavoltage (MV) imaging detectors have been the focus of research by many groups in recent years. We have been working with segmented CdWO4 crystals in contact with photodiodes in our lab. The present study uses both x-ray and optical photon transport Monte Carlo simulations to analyze the effects of scintillation crystal height, septa material, beam divergence, and beam spectrum on the modulation transfer function, MTF(f) and zero frequency detective quantum efficiency, DQE(0), of a theoretical area detector. The theoretical detector is comprised of tall, segmented CdWO4 crystals and two dimensional photodiode arrays with a pitch of 1 mm and a fill factor of 72%. Increasing the crystal height above 10 mm does not result in an improvement in the DQE(0) if the reflection coefficient of the septa is less than 0.8. For a reflection coefficient of 0.975 for the septa, there is a continual gain in the DQE(0) up to 30 mm tall crystals. Similar calculations show that employing a 3.5 MV beam without a flattening filter increases the DQE(0) for 20 mm tall crystals by 9% compared to a typical 6 MV beam with a flattening filter. The severe degradations due to beam divergence on MTF(f) are quantified and suggest the use of focused detectors in MV imaging. It is found that when the effect of optical photons is considered, the presence of divergence can appear as a shift in the location of the input signal as well as loss of spatial resolution. PMID- 17278807 TI - 2D/3D image fusion for accurate target localization and evaluation of a mask based stereotactic system in fractionated stereotactic radiotherapy of cranial lesions. AB - The purpose of this study was to evaluate the accuracy of a two-dimensional (2D) to three-dimensional (3D) image-fusion-guided target localization system and a mask based stereotactic system for fractionated stereotactic radiotherapy (FSRT) of cranial lesions. A commercial x-ray image guidance system originally developed for extracranial radiosurgery was used for FSRT of cranial lesions. The localization accuracy was quantitatively evaluated with an anthropomorphic head phantom implanted with eight small radiopaque markers (BBs) in different locations. The accuracy and its clinical reliability were also qualitatively evaluated for a total of 127 fractions in 12 patients with both kV x-ray images and MV portal films. The image-guided system was then used as a standard to evaluate the overall uncertainty and reproducibility of the head mask based stereotactic system in these patients. The phantom study demonstrated that the maximal random error of the image-guided target localization was +/-0.6 mm in each direction in terms of the 95% confidence interval (CI). The systematic error varied with measurement methods. It was approximately 0.4 mm, mainly in the longitudinal direction, for the kV x-ray method. There was a 0.5 mm systematic difference, primarily in the lateral direction, between the kV x-ray and the MV portal methods. The patient study suggested that the accuracy of the image-guided system in patients was comparable to that in the phantom. The overall uncertainty of the mask system was +/-4 mm, and the reproducibility was +/-2.9 mm in terms of 95% CI. The study demonstrated that the image guidance system provides accurate and precise target positioning. PMID- 17278809 TI - A dosimetric study on the Ir-192 high dose rate flexisource. AB - In this work, the dose rate distribution of a new Ir-192 high dose rate source (Flexisource used in the afterloading Flexitron system, Isodose Control, Veenendaal, The Netherlands) is studied by means of Monte Carlo techniques using the GEANT4 code. The dosimetric parameters of the Task Group No. 43 Report (TG43) formalism and two-dimensional rectangular look-up tables have been obtained. PMID- 17278810 TI - A dosimetric comparison of 169Yb and 192Ir for HDR brachytherapy of the breast, accounting for the effect of finite patient dimensions and tissue inhomogeneities. AB - Monte Carlo simulation dosimetry is used to compare 169Yb to 192Ir for breast high dose rate (HDR) brachytherapy applications using multiple catheter implants. Results for bare point sources show that while 169Yb delivers a greater dose rate per unit air kerma strength at the radial distance range of interest to brachytherapy in homogeneous water phantoms, it suffers a greater dose rate deficit in missing scatter conditions relative to 192Ir. As a result of these two opposing factors, in the scatter conditions defined by the presence of the lung and the finite patient dimensions in breast brachytherapy the dose distributions calculated in a patient equivalent mathematical phantom by Monte Carlo simulations for the same implant of either 169Yb or 1921r commercially available sources are found comparable. Dose volume histogram results support that 169Yb could be at least as effective as 192Ir delivering the same dose to the lung and slightly reduced dose to the breast skin. The current treatment planning systems' approach of employing dosimetry data precalculated in a homogeneous water phantom of given shape and dimensions, however, is shown to notably overestimate the delivered dose distribution for 169Yb. Especially at the skin and the lung, the treatment planning system dose overestimation is on the order of 15%-30%. These findings do not undermine the potential of 169Yb HDR sources for breast brachytherapy relative to the most commonly used 192Ir HDR sources. They imply, however, that there could be a need for the amendment of dose calculation algorithms employed in clinical treatment planning of particular brachytherapy applications, especially for intermediate photon energy sources such as 169Yb. PMID- 17278811 TI - An Egsnrc investigation of the P(TP) correction factor for ion chambers in kilovoltage X rays. AB - As part of the standard practice for obtaining consistent ion chamber measurements with cavities open to the surrounding atmosphere, the raw measured response is corrected to the response at a reference temperature and pressure using the standard temperature-pressure correction factor (P(TP)). In this study, the EGSnrc Monte Carlo code was used to investigate the validity of the P(TP) correction factor for kilovoltage x rays incident on various geometrically distinct ion chambers. The calculated P(TP)-corrected chamber response deviated by over 2% relative to expected values for a 40 kV spectrum incident on a graphite thimble chamber at an air density typical of Mexico City. The relative deviation from the expected response was much worse for a large spherical graphite chamber, exceeding 16% at an air density of 0.6 kg/m3 (approximately 0.5 atm at 22 degrees C) for the same beam energy. The breakdown of the P(TP) correction factor was also observed for a 26 kV mammography spectrum incident on two mammography chambers. For 60Co beams, the P(TP) correction factor behaved as expected. For day-to-day variations in pressure, only a negligible of the P(TP) correction factor was observed with low x-ray energies. Factors contributing to the breakdown of the P(TP) correction factor at low x-ray energies and large pressure variations, such as the range of electrons, the material of the wall, the chamber dimensions and air-photon interactions, are discussed in depth. PMID- 17278812 TI - Automated detection of a prostate Ni-Ti stent in electronic portal images. AB - Planning target volumes (PTV) in fractionated radiotherapy still have to be outlined with wide margins to the clinical target volume due to uncertainties arising from daily shift of the prostate position. A recently proposed new method of visualization of the prostate is based on insertion of a thermo-expandable Ni Ti stent. The current study proposes a new detection algorithm for automated detection of the Ni-Ti stent in electronic portal images. The algorithm is based on the Ni-Ti stent having a cylindrical shape with a fixed diameter, which was used as the basis for an automated detection algorithm. The automated method uses enhancement of lines combined with a grayscale morphology operation that looks for enhanced pixels separated with a distance similar to the diameter of the stent. The images in this study are all from prostate cancer patients treated with radiotherapy in a previous study. Images of a stent inserted in a humanoid phantom demonstrated a localization accuracy of 0.4-0.7 mm which equals the pixel size in the image. The automated detection of the stent was compared to manual detection in 71 pairs of orthogonal images taken in nine patients. The algorithm was successful in 67 of 71 pairs of images. The method is fast, has a high success rate, good accuracy, and has a potential for unsupervised localization of the prostate before radiotherapy, which would enable automated repositioning before treatment and allow for the use of very tight PTV margins. PMID- 17278813 TI - Intensity modulated radiation therapy with irregular multileaf collimated field: a dosimetric study on the penumbra region with different leaf stepping patterns. AB - Using a Varian 21 EX linear accelerator with a multileaf collimator (MLC) of 120 leaves, the penumbra regions of beam profiles within an irregular multileaf collimated fields were studied. MLC fields with different leaf stepping angles from 21.8 degrees to 68.2 degrees were used. Beam profiles in different directions: (1) along the cross-line and in-line axis, (2) along the leaf stepping edges of the field, and (3) parallel to the stepping edges but in the middle of the field, were measured and calculated using Kodak XV radiographic film and Pinnacle3 treatment planning system version 7.4f. These beam profiles were measured and calculated at source to axis distance= 100 cm with 5 cm of solid water slab on top. On the one hand, for both cross-line and in-line beam profiles, the penumbra widths of 20%-80% did not vary with the leaf stepping angles and were about 0.4 cm. On the other hand, the penumbra widths of 10%-90% of the above two profiles varied with the stepping angles and had maximum widths of about 1.9 cm (cross-line) and 1.65 cm (in-line) for stepping angles of 38.7 degrees and 51.3 degrees , respectively. For profiles crossing the "rippled" stepping edges of the field, the penumbra widths (10%-90%) at the regions between two opposite leaves (i.e., profile end at the Y1/Y2 jaw position) decreased with the stepping angles. At the penumbra regions between two leaf edges with the tongue-and-groove structure of the same bank (i.e., profile end at the X1/X2 jaw position), the penumbra widths increased with the stepping angles. When the penumbra widths were measured between two opposite leaf edges and at corners between two leaves, the widths first decreased with the stepping angles and then increased beyond the minimum width point at stepping angle of 45 degrees. The penumbra width (10%-90%) measured at the leaf edge was larger than that at the corner. For the beam profiles calculated using Pinnacle3, it is found that the results agreed well with the measurements along the cross-line and in-line axis, while there was a deviation for the profiles along the leaf stepping edge of the field compared to the film measurements. The measured results in this study can help us to understand the dosimetric effect of the leaf stepping (due to finite leaf width), tongue-and-groove and rounded leaf end structure in the penumbra region of an irregular MLC field. A more dedicated penumbra model can be developed for the treatment planning system. PMID- 17278814 TI - Monte Carlo simulations of dose near a nonradioactive gold seed. AB - The relative doses and hot/cold spot positions around a non-radioactive gold seed, irradiated by a 6 or 18 MV photon beam in water, were calculated using Monte Carlo simulation. Phase space files of 6 and 18 MV photon beams with a field size of 1 x 1 cm2 were generated by a Varian 21 EX linear accelerator using the EGSnrc and BEAMnrc code. The seed (1.2 x 1.2 x 3.2 mm3) was positioned at the isocenter in a water phantom (20 x 20 x 20 cm2) with source-to-axis distance = 100 cm. For the single beam geometry, the relative doses (normalized to the dose at 5 mm distance above the isocenter) at the upstream seed surface were calculated to be 1.64 and 1.56 for the 6 and 18 MV beams respectively when the central beam axis (CAX) is parallel to the width of the seed. These doses were slightly higher than those (1.58 and 1.52 for 6 and 18 MV beams respectively) calculated when the CAX is perpendicular to the width of the seed. Compared to the relative dose profiles with the same beam geometry without the seed in the water phantom, the presence of the seed affects the dose distribution at about 3 mm distance beyond both the upstream and downstream seed surface. For a pair of opposing beams with equal and unequal beam weight, the hot and cold spots of both opposing beams were mixed. For a 360 degree photon arc around the longitudinal axis of the seed, the relative dose profile along the width of the seed was similar to that of the opposing beam pair, except the former geometry has a larger dose gradient near the seed surface. In this study, selected results from our simulation were compared to previous measurements using film dosimetry. PMID- 17278815 TI - Prospects for quantitative two-dimensional radiochromic film dosimetry for low dose-rate brachytherapy sources. AB - Radiochromic film (RCF) has been shown to be a precise and accurate two dimensional dosimeter for acute exposure radiation fields. However, "temporal history" mismatch between calibration and brachytherapy films due to RCF dose rate effects could introduce potentially large uncertainties in low dose-rate (LDR) brachytherapy absolute dose measurement. This article presents a quantitative evaluation of the precision and accuracy of a laser scanner-based RCF-dosimetry system and the effect of the temporal history mismatch in LDR absolute dose measurement. MD-55-2 RCF was used to measure absolute dose for a low dose-rate 137Cs brachytherapy source using both single- and double-exposure techniques. Dose-measurement accuracy was evaluated by comparing RCF to Monte Carlo photon-transport simulation. The temporal history mismatch effect was investigated by examining dependence of RCF accuracy on irradiation-to densitometry time interval. The predictions of the empirical cumulative dose superposition model (CDSM) were compared with measurements. For the double exposure technique, the agreement between measurement and Monte Carlo simulation was better than 4% in the 3-60 Gy dose range with measurement precisions (coverage factor k = 1) of <2% and <6% for the doses greater or less than 3 Gy, respectively. The overall uncertainty (k = 1) of dose rate/air-kerma strength measurements achievable by this dosimetry system for a spatial resolution of 0.1 mm is less than 4% for doses greater than 5 Gy. The measured temporal history mismatch systematic error is about 1.8% for a 48 h postexposure time when using the double exposure technique and agrees with CDSM's prediction qualitatively. This work demonstrates that the model MD-55-2 RCF detector has the potential to support quantitative dose measurements about LDR brachytherapy sources with precision and accuracy better than that of previously described dosimeters. The impacts of this work on the future use of new type of RCF were also discussed. PMID- 17278816 TI - Investigations of different kilovoltage X-ray energy for three-dimensional converging stereotactic radiotherapy system: Monte Carlo simulations with CT data. AB - We are investigating three-dimensional converging stereotactic radiotherapy (3DCSRT) with suitable medium-energy x rays as treatment for small lung tumors with better dose homogeneity at the target. A computed tomography (CT) system dedicated for non-coplanar converging radiotherapy was simulated with BEAMnrc (EGS4) Monte-Carlo code for x-ray energy of 147.5, 200, 300, and 500 kilovoltage (kVp). The system was validated by comparing calculated and measured percentage of depth dose in a water phantom for the energy of 120 and 147.5 kVp. A thorax phantom and CT data from lung tumors (<20 cm3) were used to compare dose homogeneities of kVp energies with MV energies of 4, 6, and 10 MV. Three non coplanar arcs (0 degrees and +/-25 degrees ) around the center of the target were employed. The Monte Carlo dose data format was converted to the XiO RTP format to compare dose homogeneity, differential, and integral dose volume histograms of kVp and MV energies. In terms of dose homogeneity and DVHs, dose distributions at the target of all kVp energies with the thorax phantom were better than MV energies, with mean dose absorption at the ribs (human data) of 100%, 85%, 50%, 30% for 147.5, 200, 300, and 500 kVp, respectively. Considering dose distributions and reduction of the enhanced dose absorption at the ribs, a minimum of 500 kVp is suitable for the lung kVp 3DCSRT system. PMID- 17278817 TI - Estimation of white matter connectivity based on a three-dimensional directional diffusion function in diffusion tensor MRI. AB - Diffusion tensor (DT) magnetic resonance imaging (MRI) provides the directional information of local neuronal fibers, and has been used to estimate the neuroanatomical connectivity in the cerebral white matter. Several methods for white matter tractography have been developed based on DT-MRI. However, it has been difficult to estimate the white matter tract pathways in the fiber crossing and branching region because of the ambiguity of the principal eigenvector and/or low anisotropy due to the partial volume effect. In this paper, we proposed a new method for white matter tractography, which permits fiber tract branching and passing through crossing regions. Our tractography method is based on a three dimensional (3D) directional diffusion function (DDF), which was given by a 3D anisotropic Gaussian function defined by normalized three eigenvalues and their corresponding eigenvectors of DT. The DDF was used for generation of a 3D directional diffusion field and for determination of the connectivity between the voxels in fiber tracking. To extract the white matter tract region, DDF-based tractography (DDFT) method used the directional diffusion field instead of a threshold fractional anisotropy map, which has been used in the conventional methods, so that low anisotropy voxels in the branching and crossing regions may be included. We applied the DDFT method and two conventional tractography methods (a streamline technique and a tensorline algorithm) to DT-MRI data of five normal subjects for visualizing the pyramidal tract. Our method visualized the pathways connected to a large portion of the primary motor cortex, including foot, hand and face motor areas, passing through the crossing regions with other white matter tracts in all subjects, whereas the conventional methods showed only a small portion of the pyramidal tract. The pyramidal tract pathways estimated by our method were consistent with the neuroanatomical knowledge. In conclusion, the DDFT method may be useful in assisting neuroradiologists in estimating the white matter tracts. PMID- 17278818 TI - Efficient projection and backprojection scheme for spherically symmetric basis functions in divergent beam geometry. AB - In cone-beam transmission tomography the measurements are performed with a divergent beam of x-rays. The reconstruction with iterative methods is an approach that offers the possibility to reconstruct the corresponding images directly from these measurements. Another approach based on spherically symmetric basis functions (blobs) has been reported with results demonstrating a better image quality for iterative reconstruction algorithms. When combining the two approaches (i.e., using blobs in iterative cone-beam reconstruction of divergent rays) the problem of blob sampling without introducing aliasing must be addressed. One solution to this problem is to select a blob size large enough to ensure a sufficient sampling, but this prevents a high resolution reconstruction, which is not desired. Another solution is a heuristic low-pass filtering, which removes this aliasing, but neglects the different contributions of blobs to the absorption depending on the spatial position in the volume and, therefore, cannot achieve the best image quality. This article presents a model of sampling the blobs which is motivated by the beam geometry. It can be used for high resolution reconstruction and can be implementedefficiently. PMID- 17278819 TI - Computerized detection of vertebral compression fractures on lateral chest radiographs: preliminary results with a tool for early detection of osteoporosis. AB - Vertebral fracture (or vertebral deformity) is a very common outcome of osteoporosis, which is one of the major public health concerns in the world. Early detection of vertebral fractures is important because timely pharmacologic intervention can reduce the risk of subsequent additional fractures. Chest radiographs are used routinely for detection of lung and heart diseases, and vertebral fractures can be visible on lateral chest radiographs. However, investigators noted that about 50% of vertebral fractures visible on lateral chest radiographs were underdiagnosed or under-reported, even when the fractures were severe. Therefore, our goal was to develop a computerized method for detection of vertebral fractures on lateral chest radiographs in order to assist radiologists' image interpretation and thus allow the early diagnosis of osteoporosis. The cases used in this study were 20 patients with severe vertebral fractures and 118 patients without fractures, as confirmed by the consensus of two radiologists. Radiologists identified the locations of fractured vertebrae, and they provided morphometric data on the vertebral shape for evaluation of the accuracy of detecting vertebral end plates by computer. In our computerized method, a curved search area, which included a number of vertebral end plates, was first extracted automatically, and was straightened so that vertebral end plates became oriented horizontally. Edge candidates were enhanced by use of a horizontal line-enhancement filter in the straightened image, and a multiple thresholding technique, followed by feature analysis, was used for identification of the vertebral end plates. The height of each vertebra was determined from locations of identified vertebral end plates, and fractured vertebrae were detected by comparison of the measured vertebral height with the expected height. The sensitivity of our computerized method for detection of fracture cases was 95% (19/20), with 1.03 (139/135) false-positive fractures per image. The accuracy of identifying vertebral end plates, marked by radiologists in a morphometric study, was 76.6% (400/522) and 70.9% (420/592) for cases used for training and those for testing, respectively. We prepared 32 additional fracture cases for a validation test, and we examined the detection accuracy of our computerized method. The sensitivity for these cases was 75% (24/32) at 1.03 (33/32) false positive fractures per image. Our preliminary results show that the automated computerized scheme for detecting vertebral fractures on lateral chest radiographs has the potential to assist radiologists in detecting vertebral fractures. PMID- 17278820 TI - Monte Carlo and experimental dosimetry of an 1251 brachytherapy seed. AB - We have performed a comprehensive dosimetric characterization of the Oncura model 6711 125I seed using both experimental [LiF thermoluminscent dosimetry (TLD)] and theoretical (Monte Carlo photon transport) methods. In addition to determining the dosimetric parameters of the 6711, this report quantified: (1) the angular dependence of LiF TLD energy response functions for both point and volume detectors in water, poly(methylmethacrylate), and solid water media; and (2) the contribution of underlying geometric uncertainties to the overall uncertainty of Monte Carlo derived dosimetric parameters according to the National Institute of Standards and Technology Report 1297 methodology. The theoretical value for the dose rate constant in water was 0.942 cGy U(-1) h(-1)+/-1.76% [combined standard uncertainty (CSU) with coverage factor k=1] and the experimental value was 0.971 cGy U(-1) h(-1)+/-6.1%. Agreement between experimental and theoretical radial dose function values was well within the k= 1 CSU, while agreement between experimental and theoretical anisotropy function values was within the k= 1 CSU only after incorporating the use of polar angle-dependent energy response functions. The angular dependence of the relative energy response was found to have a complex and significant dependence on measurement medium and internal geometry of the source. PMID- 17278821 TI - Radiative transport in fluorescence-enhanced frequency domain photon migration. AB - Small animal optical tomography has significant, but potential application for streamlining drug discovery and pre-clinical investigation of drug candidates. However, accurate modeling of photon propagation in small animal volumes is critical to quantitatively obtain accurate tomographic images. Herein we present solutions from a robust fluorescence-enhanced, frequency domain radiative transport equation (RTE) solver with unique attributes that facilitate its deployment within tomographic algorithms. Specifically, the coupled equations describing time-dependent excitation and emission light transport are solved using discrete ordinates (SN) angular differencing along with linear discontinuous finite-element spatial differencing on unstructured tetrahedral grids. Source iteration in conjunction with diffusion synthetic acceleration is used to iteratively solve the resulting system of equations. This RTE solver can accurately and efficiently predict ballistic as well as diffusion limited transport regimes which could simultaneously exist in small animals. Furthermore, the solver provides accurate solutions on unstructured, tetrahedral grids with relatively large element sizes as compared to commonly employed solvers that use step differencing. The predictions of the solver are validated by a series of frequency-domain, phantom measurements with optical properties ranging from diffusion limited to transport limited propagation. Our results demonstrate that the RTE solution consistently matches measurements made under both diffusion and transport-limited conditions. This work demonstrates the use of an appropriate RTE solver for deployment in small animal optical tomography. PMID- 17278822 TI - An analysis of the treatment couch and control system dynamics for respiration induced motion compensation. AB - Sophisticated methods for real-time motion compensation include using the linear accelerator, MLC, or treatment couch. To design such a couch, the required couch and control system dynamics need to be investigated. We used an existing treatment couch known as the Hexapod to gain insight into couch dynamics and an internal model controller to simulate feedback control of respiration-induced motion. The couch dynamics, described using time constants and dead times, were investigated using step inputs. The resulting data were modeled as first and second order systems with dead time. The couch was determined to have a linear response for step inputs < or = 1 cm. Motion data from 12 patients were obtained using a skin marker placed on the abdomen of the patient and the marker data were assumed to be an exact surrogate of tumor motion. The feedback system was modeled with the couch as a second-ordersystem and the controller as a first order system. The time constants of the couch and controller and the dead times were varied starting with parameters obtained from the Hexapod couch and the performance of the feedback system was evaluated. The resulting residual motion under feedback control was generally <0.3 cm when a fast enough couch was simulated. PMID- 17278823 TI - Clinical assessment of three-dimensional ultrasound prostate localization for external beam radiotherapy. AB - Three-dimensional ultrasound localization has been performed for external beam prostate treatments at our institution since September 2001. This article presents data from the daily shifts for 221 patients and 5005 fractions, and the results of tests performed to assess the system's performance under clinical conditions. Three tests are presented: (1) To measure the accuracy of the shifts, eight patients treated on a helical tomotherapy machine were localized daily using both ultrasound (US) and a megavoltage computed tomography (MVCT) scan. Comparison of the shifts showed that US localization improved alignment for six of the eight patients when compared to alignment using skin marks alone. The mean US-MVCT vector for these six patients was 3.1+/-1.3 mm, compared to 5.1+/-2.1 mm between the MVCT and the skin marks. The other two patients were identified as poor candidates for US prior to their first treatment fraction. (2) To assess the extent of intrafraction motion, US localization was repeated after treatment for six patients and a total of 29 fractions. The mean intrafraction prostate shift was 1.9+/-1.0 mm, and the shift was within the 3 mm localization uncertainty [Tome et al., Med. Phys. 29, 1781-1788 (2002); in New Technologies in Radiation Oncology, edited by W. Schlegel, T. Bortfelde, and A. Grosu (Springer, Berlin, 2005)] of the system for 25 of 29 fractions. (3) To assess the interuser variation in shifts, four experienced operators independently localized five patients for five consecutive fractions. The standard deviation of the users' shifts was found to be approximately the same as the system's localization uncertainty. For shifts larger than the system localization uncertainty, the standard deviation of the users' shifts was nearly always much smaller than the mean shift. Taken together with the results of the US-MVCT comparison, this indicates that the shifts improved patient localization despite differences between users. PMID- 17278824 TI - Multiobjective optimization with a modified simulated annealing algorithm for external beam radiotherapy treatment planning. AB - Inverse planning in external beam radiotherapy often requires a scalar objective function that incorporates importance factors to mimic the planner's preferences between conflicting objectives. Defining those importance factors is not straightforward, and frequently leads to an iterative process in which the importance factors become variables of the optimization problem. In order to avoid this drawback of inverse planning, optimization using algorithms more suited to multiobjective optimization, such as evolutionary algorithms, has been suggested. However, much inverse planning software, including one based on simulated annealing developed at our institution, does not include multiobjective oriented algorithms. This work investigates the performance of a modified simulated annealing algorithm used to drive aperture-based intensity-modulated radiotherapy inverse planning software in a multiobjective optimization framework. For a few test cases involving gastric cancer patients, the use of this new algorithm leads to an increase in optimization speed of a little more than a factor of 2 over a conventional simulated annealing algorithm, while giving a close approximation of the solutions produced by a standard simulated annealing. A simple graphical user interface designed to facilitate the decision making process that follows an optimization is also presented. PMID- 17278825 TI - Targeted 2D/3D registration using ray normalization and a hybrid optimizer. AB - X-ray images are often used to guide minimally invasive procedures in interventional radiology. The use of a preoperatively obtained 3D volume can enhance the visualization needed for guiding catheters and other surgical devices. However, for intraoperative usefulness, the 3D dataset needs to be registered to the 2D x-ray images of the patient. We investigated the effect of targeting subvolumes of interest in the 3D datasets and registering the projections with C-arm x-ray images. We developed an intensity-based 2D/3D rigid body registration using a Monte Carlo-based hybrid algorithm as the optimizer, using a single view for registration. Pattern intensity (PI) and mutual information (MI) were two metrics tested. We used normalization of the rays to address the problems due to truncation in 3D necessary for targeting. We tested the algorithm on a C-arm x-ray image of a pig's head and a 3D dataset reconstructed from multiple views of the C-arm. PI and MI were comparable in performance. For two subvolumes starting with a set of initial poses from +/-15 mm in x, from +/-3 mm (random), in y and z and +/-4 deg in the three angles, the robustness was 94% for PI and 91% for MI, with accuracy of 2.4 mm (PI) and 2.6 mm (MI), using the hybrid algorithm. The hybrid optimizer, when compared with a standard Powell's direction set method, increased the robustness from 59% (Powell) to 94% (hybrid). Another set of 50 random initial conditions from [+/ 20] mm in x,y,z and [+/-10] deg in the three angles, yielded robustness of 84% (hybrid) versus 38% (Powell) using PI as metric, with accuracies 2.1 mm (hybrid) versus 2.0 mm (Powell). PMID- 17278826 TI - Dose point kernel for boron-11 decay and the cellular S values in boron neutron capture therapy. AB - The study of the radiobiology of boron neutron capture therapy is based on the cellular level dosimetry of boron-10's thermal neutron capture reaction 10B(n,alpha)7Li, in which one 1.47 MeV helium-4 ion and one 0.84 MeV lithium-7 ion are spawned. Because of the chemical preference of boron-10 carrier molecules, the dose is heterogeneously distributed in cells. In the present work, the (scaled) dose point kernel of boron-11 decay, called 11B-DPK, was calculated by GEANT4 Monte Carlo simulation code. The DPK curve drops suddenly at the radius of 4.26 microm, the continuous slowing down approximation (CSDA) range of a lithium-7 ion. Then, after a slight ascending, the curve decreases to near zero when the radius goes beyond 8.20 microm, which is the CSDA range of a 1.47 MeV helium-4 ion. With the DPK data, S values for nuclei and cells with the boron-10 on the cell surface are calculated for different combinations of cell and nucleus sizes. The S value for a cell radius of 10 microm and a nucleus radius of 5 microm is slightly larger than the value published by Tung et al. [Appl. Radiat. Isot. 61, 739-743 (2004)]. This result is potentially more accurate than the published value since it includes the contribution of a lithium-7 ion as well as the alpha particle. PMID- 17278827 TI - A fast tube of response ray-tracer. AB - A ray-tracing algorithm is proposed to quickly approximate volumes of intersection between an arbitrary tube of response and a voxel array. The method is based on the idea of the Wu antialiased line tracer that is well known in the computer graphics community. However, our method works in three dimensions and supports arbitrary symmetrical response profile functions. The inner loop implementation does not use any conditional branching and is aware of low-level optimization strategies. The running speed of a fast incremental Siddon routine appears to be about 60% slower than our algorithm. PMID- 17278828 TI - Application of an inverse kernel concept to Monte Carlo based IMRT. AB - Inverse treatment planning by means of pencil beam algorithms can lead to errors in the calculation of dose in areas without secondary electron equilibrium. Monte Carlo (MC) simulations give accurate results in such areas but result in increased computation times. We present a new, so-called inverse kernel concept that offers MC precision in inverse treatment planning with acceptable computation times and memory consumption. Inverse kernels are matrices that describe the dose contribution from all bixels of a beam to a distinct voxel of the patient phantom. The concept is similar to other generalized pencil-beam concepts, except that inverse kernel elements are precalculated using a single MC simulation and stored as binary trees. In this procedure a modified MC code (XVMC) is applied to trace the photon history for each dose deposition. Iterative optimization is then applied in a second step. The inverse process is separated into (i) a slower MC simulation and (ii) a faster iterative optimization, followed by (iii) the segmentation procedure, and (iv) a final MC dose calculation step including a segment weight reoptimization. Inverse kernel optimization, or IKO, with segmentation and reoptimization steps is demonstrated by means of a lung cancer case. To demonstrate the superiority of an inverse MC system over pencil-beam or collapsed-cone based systems, the final result of the IKO is compared to plans where all segments have been calculated by pencil beam or collapsed cone, respectively. Dose-volume histograms and dose-difference histograms show remarkable differences, which can be attributed to systematic errors in both algorithms. IKO is a precise, nonhybrid, inverse MC treatment planning system which suits current clinical needs, as several optimization steps can follow one single MC-simulation step for a distinct beam setup. PMID- 17278829 TI - Robustness and complexity of a minimally invasive vascular intervention simulation system. AB - Minimally invasive vascular interventions offer advantages over open surgery. Thorough training is needed to master the skills required to correctly perform these minimally invasive interventions. Simulation is becoming a potential alternative for training. We have developed the foundation, i.e., the algorithmics and models, for a minimally invasive vascular intervention simulation system focusing on guide-wire manipulations. In this article we address the robustness, accuracy, and complexity of this foundation using a phantom. To this end the theory on which the simulation is based is used to formulate constraints on the simulation parameters. Furthermore, the parameter space has been explored in order to optimize the trade-off we are facing: accuracy versus speed of the simulation. A physical experiment setup has been designed that allows us to obtain ground-truth data. The accuracy of the simulation has been determined by comparing physical experimental results with various simulations. For multiple combinations of parameter settings the simulation supplies a guide-wire configuration with a root-mean-square error around 1 mm. The results show that the speed of the simulation is still an issue and needs to be improved. Nevertheless, the results also indicate that the developed algorithms and models are a robust foundation to build a simulation system on. PMID- 17278830 TI - The international scope of Medical Physics: an editorial. PMID- 17278831 TI - Film/screen speed. PMID- 17278832 TI - Dynamics of the Fas- and stress-induced apoptosis of human neutrophils under the action of endotoxins. PMID- 17278833 TI - The velocity of gliding of a freshwater gastropod depends on its muscular activity. PMID- 17278834 TI - Fusion of nerve fibers. PMID- 17278835 TI - Fatty acid composition of phospholipids of the cell nuclei from the rat brain after hypoxia at different periods of ontogeny. PMID- 17278836 TI - The role of the actin cytoskeleton in the regulation of Na+ transport by phosphatidylinositol kinases in the frog skin. PMID- 17278837 TI - The dynamics of the body surface cardioelectric field in one-day-old rats. PMID- 17278838 TI - Complex orientation selectivity of neurons of the visual system. PMID- 17278839 TI - Specific binding of semax in different regions of the rat brain. PMID- 17278840 TI - Seasonal dynamics of the helminthofauna of gulls of the genus Larus from the Barents Sea as exemplified by the western Murman region. PMID- 17278841 TI - Bank and red vole hybridization under experimental conditions. PMID- 17278842 TI - Thyroxin as a growth stimulator for the fry of Oncorhynchus gorbuscha (Walb.) from the Barents Sea. PMID- 17278843 TI - Distribution of small mammals in three layers of South Vietnam rainforest. PMID- 17278844 TI - Defense behavior of moose. PMID- 17278845 TI - Extracellular antifungal glycolipids of Cryptococcus humicola yeasts. PMID- 17278846 TI - Trimeric coelom organization in the larvae of Phoronopsis harmeri Pixell, 1912 (Phoronida, Lophophorata). PMID- 17278847 TI - Role of stem cells in plant morphogenesis. PMID- 17278848 TI - Chromosomal instability and cranial asymmetry in the mole-vole Ellobius talpinus Pallas, 1770 polymorphic for coat coloration. PMID- 17278849 TI - Effect of octopamine on Drosophila melanogaster reproduction is mediated by gonadotropins. PMID- 17278850 TI - Giant actinotroch, a larva of Phoronida from the South China Sea: the giant larva phenomenon. PMID- 17278851 TI - Effects of O-hydrometalloatranes on the growth of cultured plant cells. PMID- 17278852 TI - Allozyme heterozygosity, metabolic rate, sexual maturation rate, and longevity. PMID- 17278853 TI - Study of the morphological diversity of bacteriophages in Lake Baikal. PMID- 17278854 TI - Spermatogenesis pattern in SAMP1 mice prone to accelerated senescence: an experimental study. PMID- 17278856 TI - Fee limits and controls--history revisited. PMID- 17278857 TI - Good leadership is not tidy business. PMID- 17278855 TI - The leading role of actinobacteria in aerobic cellulose degradation in Sphagnum peat bogs. PMID- 17278858 TI - Demographics are destiny. PMID- 17278859 TI - TDA-endorsed service. PMID- 17278860 TI - Children and parents and medical decisions. PMID- 17278861 TI - Talking to each other about universal health care: do values belong in the discussion? PMID- 17278863 TI - Shades of gray: new insights into the vegetative state. PMID- 17278862 TI - ANT vs. SCNT. PMID- 17278864 TI - Investigational drugs and the constitution. PMID- 17278865 TI - Two cheers for conscience exceptions. PMID- 17278866 TI - Moral priorities in a teaching hospital. PMID- 17278867 TI - Controversial medical treatment and the right to health care. PMID- 17278868 TI - The sociobiology of humanism. PMID- 17278869 TI - Where nowhere can lead you. PMID- 17278870 TI - Children's competence to consent to medical treatment. AB - As a study involving diabetes care demonstrates, children sometimes have a much more sophisticated capacity for taking charge of their own health care decisions than is usually recognized in bioethics. Protecting these children from their disease means involving them in their treatment as much as possible, helping them to understand it and take responsibility for it so that they can navigate the multitude of daily decisions that become part of the diabetes medical regimen. PMID- 17278871 TI - Liberal eugenics and human nature. Against Habermas. AB - In the course of developing his arguments against making genetic enhancements to one's children, Habermas assumes that a clear line can be drawn between the natural and the manufactured. But given the current state of medical science, this is precisely what we can no longer take for granted. PMID- 17278872 TI - Privatizing the Department of Defense: a proposal. PMID- 17278873 TI - Asset tracking systems. AB - Asset tracking systems are used in healthcare to find objects--medical devices and other hospital equipment--and to record the physical location of those objects over time. Interest in asset tracking is growing daily, but the technology is still evolving, and so far very few systems have been implemented in hospitals. This situation is likely to change over the next few years, at which point many hospitals will be faced with choosing a system. We evaluated four asset tracking systems from four suppliers: Agility Healthcare Solutions, Ekahau, Radianse, and Versus Technology. We judged the systems' performance for two "levels" of asset tracking. The first level is basic locating--simply determining where in the facility an item can be found. This may be done because the equipment needs routine inspection and preventive maintenance or because it is required for recall purposes; or the equipment may be needed, often urgently, for clinical use. The second level, which is much more involved, is inventory optimization and workflow improvement. This entails analyzing asset utilization based on historical location data to improve the use, distribution, and processing of equipment. None of the evaluated products is ideal for all uses- each has strengths and weaknesses. In many cases, hospitals will have to select a product based on their specific needs. For example, they may need to choose between a supplier whose system is easy to install and a supplier whose tags have a long battery operating life. PMID- 17278874 TI - Clarifying the AHA guidelines for CPR and defibrillation. AB - The American Heart Association's (AHA) newest Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care include sub stantial changes, and hospitals will need to modify processes and equipment to implement them. This article clarifies the new guidelines and describes the rationale behind each change. Also, it describes the steps that leading defibrillator suppliers are taking to make their products comply. In some cases, these product changes will require hospitals to install software-based upgrades or modify product configurations. PMID- 17278875 TI - Hazard report. Zero calibration and pressure drift problems with Argon Medical CDX III, CDXpress transducers. PMID- 17278876 TI - Talk to the specialist. Electrosurgery vs. electrocautery: untangling the terminology. PMID- 17278877 TI - Heat shock protein 10 and signal transduction: a "capsula eburnea" of carcinogenesis? AB - To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of Hsp60 in the Hsp60/10 protein folding machine. Only recently, Hsp10 was reported to interact with proteins involved in deoxyribonucleic acid checkpoint inactivation, termination of M-phase, messenger ribonucleic acid export, import of nuclear proteins, nucleocytoplasmic transport, and pheromone signaling pathways. At the same time, Hsp10 expression can be up-regulated in cancer cells, because it accumulates as the cell transformation progresses. Recent data suggest that Hsp10 may be not only a component of the folding machine but also an active player of the cell signaling network, influencing cell cycle, nucleocytoplasmic transport, and metabolism, with putative roles in the lack of cell differentiation and in the inhibition of apoptosis. In this review, we revise the involvement of Hsp10 in signal transduction pathways and its possible role in cancer etiology. PMID- 17278878 TI - Activities of the cochaperones Hap46/BAG-1M and Hap50/BAG-1L and isoforms. AB - Since their discovery about a decade ago, human Hap46/BAG-1M, the larger isoform Hap50/BAG-1L, and related structures have caused quite some astonishment because of the seemingly unlimited array of possible interaction partners belonging to completely unrelated protein families. This problem was partially resolved when it was realized that molecular chaperones of the heat shock protein family Hsp70 are major primary association partners, which in turn, are able to bind a wide variety of unrelated protein structures, thus forming ternary complexes. Moreover, the protein folding activity of Hsp70 chaperones is affected; hence, the designation "cochaperones." Although many different proteins require mediation by Hsp70 chaperones for interactions with Hap50/BAG-1L, Hap46/BAG-1M, and isoforms, several other partner proteins are able to associate directly. In addition, Hap46/BAG-1M and Hap50/BAG-1L are also able to interact with DNA by making use of a positively charged region close to the amino terminal end of the polypeptide chain. This is the molecular basis for their effects on transcriptional activities, which are emphasized in this review and for which a molecular model is presented. PMID- 17278879 TI - Effect of blood handling on extracellular Hsp72 concentration after high intensity exercise in humans. AB - Heat shock protein 72 (Hsp72) has been detected in the peripheral circulation of humans. Because intracellular Hsp72 binds to aggregated proteins, we hypothesized that postexercise plasma-derived Hsp72 concentrations would be greater than serum derived Hsp72 because of binding of Hsp72 to aggregated clotting proteins in serum. Postexercise serum, heparin, and ethylenediaminetetraacetic acid (EDTA) samples were collected from 9 recreationally active males and were analyzed for Hsp72 by enzyme-linked immunosorbent assay. In line with our hypothesis, EDTA treated blood was significantly higher in Hsp72 concentration than all other treatments (P < or = 0.001), whilst heparin plasma (LH) was significantly higher than serum derived on ice (SI) and at room temperature (SR) (P < 0.05; EDTA: 6.46 +/- 0.76, LH: 2.73 +/- 2.26, SI: 0.13 +/- 0.24, SR: 0.20 +/- 0.32 ng/mL). Because previous research has tended to report serum data at the lowest point of the detectable range of the assay, it is recommended that EDTA specimen tubes be used in future investigations. PMID- 17278881 TI - Phototransduction genes are up-regulated in a global gene expression study of Drosophila melanogaster selected for heat resistance. AB - The genetic architecture underlying heat resistance remains partly unclear despite the well-documented involvement of heat shock proteins (Hsps). It was previously shown that factors besides Hsps are likely to play an important role for heat resistance. In this study, gene expression arrays were used to make replicate measurements of gene expression before and up to 64 hours after a mild heat stress treatment, in flies selected for heat resistance and unselected control flies, to identify genes differentially expressed in heat resistance selected flies. We found 108 genes up-regulated and 10 down-regulated using the Affymetrix gene expression platform. Among the up-regulated genes, a substantial number are involved in the phototransduction process. Another group of genes up regulated in selected flies is characterized by also responding to heat shock treatment several hours after peak induction of known Hsps revert to nonstress levels. These findings suggest phototransduction genes to be critically involved in heat resistance, and support a role for components of the phototransduction process in stress-sensing mechanisms. In addition, the results suggest yet uncharacterized genes responding to heat stress several hours after treatment to be involved in heat stress resistance. These findings mark an important increase in the understanding of heat resistance. PMID- 17278880 TI - Heat shock protein 70 expression is associated with inhibition of renal tubule epithelial cell apoptosis during recovery from low-protein feeding. AB - The cellular stress response can mediate cellular protection through expression of heat shock protein (Hsp70), which can interfere with the process of apoptotic cell death. Factors regulating renal epithelial cell apoptosis include angiotensin II. In the present study, we have examined the relationship between the Hsp70 expression and the apoptotic pathway in the kidneys from low-protein fed rats (8% protein). The possible cytoprotective role of Hsp70 has been evaluated during low-protein feeding and after reincorporation of 24% protein in the diet. The effect of angiotensin II AT1 receptor inhibition has also been studied. Rats were fed with a low-protein (LP) diet (8% protein) for 14 days, and then the animals were recovered by means of a normal protein diet (24% protein) (RP) for 14, 21, and 30 days, and control rats received 24% protein (NP) in the diet. LP and NP rats treated with Losartan (10 mg/kg) were also evaluated. The following methods were performed on the kidneys: terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay for apoptosis, reverse transcriptase-polymerase chain reaction assay for AT1, Bax, and Bcl-2 messenger ribonucleic acid (mRNA) expression, and immunohistochemical and Western blot for Hsp70 and caspase 3 protein expression and activity. In the LP group, the cells of the medullary ducts (MDs) showed increased apoptosis associated with weak immunoreaction for Hsp70 and decreased Hsp70 protein levels. In these animals, enhanced proapoptotic ratio Bax/Bcl-2 linked to decreased procaspase 3 protein levels with increased caspase 3 activation were demonstrated. A cytoprotection attributed to Hsp70 could be noted in the RP rats after 21 days of reincorporation of the normal diet, and in the LP-fed group treated with Losartan. In these cases, the MD cells displayed decreased apoptosis and increased Hsp70 expression in colocalization staining, and high Hsp70 levels in cytosolic fraction. A decreased proapoptotic ratio Bax/Bcl-2, associated with increased Bcl-2 mRNA, was also observed. Our results provide evidence for an antiapoptotic, cytoprotective effect of Hsp70 in kidney MD cells of rats with LP intake, when the animals were recovered with 24% protein in diet and after angiotensin II AT1 receptor inhibition. Angiotensin II seems to play a role in the pathogenesis of tubule epithelial cell apoptosis during LP feeding. PMID- 17278882 TI - Heat shock protein 70 and glycoprotein 96 are differentially expressed on the surface of malignant and nonmalignant breast cells. AB - Heat shock proteins (HSPs), which are important for a number of different intracellular functions, are occasionally found on the surface of cells. The function of heat shock protein on the cell surface is not understood, although it has been shown to be greater in some tumor cells and some virally infected cells. Surface expression of both glycoprotein 96 (gp96) and Hsp70 occurs on tumor cells, and this expression correlates with natural killer cell killing of the cells. We examined the surface expression of gp96 and Hsp70 on human breast cell lines MCF7, MCF10A, AU565, and HS578, and in primary human mammary epithelial cells by immunofluorescence microscopy and flow cytometry. The nonmalignant cell lines HS578, MCF10A, and HMEC showed no surface expression of gp96, whereas malignant cell lines MCF7 and AU565 were positive for gp96 surface expression. All of the breast cell lines examined showed Hsp70 surface expression. These results also confirm previous studies, demonstrating that Hsp70 is on the plasma membrane of tumor cell lines. Given the involvement of heat shock proteins, gp96 and Hsp70, in innate and adaptive immunity, these observations may be important in the immune response to tumor cells. PMID- 17278883 TI - TRAIL-induced apoptosis is enhanced by heat shock protein 70 expression. AB - Heat shock protein 70 (Hsp70) is a well-known inhibitor of apoptotic pathways; however, a role for Hsp70 in the modulation of death receptor-mediated apoptosis remains largely unexplored. In this study, the ability of Hsp70 to modulate tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis was examined in SW480 and CCRF-CEM cells. These lines exhibit the characteristics of type I cells (SW480, human colon adenocarcinoma), with no requirement for mitochondrial involvement to exhibit apoptosis following death receptor engagement and type II cells (CCRF-CEM, human leukemic T cell), which do require amplification of the signal through the mitochondria. Unexpectedly, expression of Hsp70 in the type II CCRF-CEM cells enhanced the extent of TRAIL-induced apoptosis, but in SW480, Hsp70 had no impact on TRAIL-induced apoptosis. The enhanced TRAIL-induced apoptosis was accompanied by an up-regulation of TRAIL receptors, R1 and R2, at the cell surface as determined by flow cytometry and at the transcriptional level as assessed by real-time polymerase chain reaction (PCR). Increased expression of Hsp70 led to up-regulated expression of p53, and chromatin immunoprecipitation combined with real-time PCR revealed increased binding of p53 to its consensus sequence in the TRAIL-R2 gene. In contrast, expression of Hsp70 in SW480 cells did not increase p53 or TRAIL-R1 or TRAIL-R2 surface expression. This result is in marked contrast to most apoptotic stresses, including TNFalpha and Fas ligand, where Hsp70 has been shown to inhibit apoptosis in type II cells. These findings suggest that in tumors retaining functional p53 and expressing high levels of Hsp70, TRAIL may be an effective therapy. PMID- 17278884 TI - Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H:quinone oxidoreductase 1 during cholestasis. AB - Bile duct ligation (BDL) causes hepatocellular oxidative stress and injury. The transcription factor nuclear factor-E2-related factor (Nrf2) induces expression of numerous genes including NAD(P)H:quinone oxidoreductase 1 (Nqo1) during periods of oxidative stress. Therefore, we hypothesized that BDL increases liver expression of mouse antioxidant genes in an Nrf2-dependent manner. BDL or sham surgeries were performed on male C57BL/6, Nrf2-null, and wild-type mice. Livers were collected at 1, 3, and 7 days after surgery for analysis of messenger ribonucleic acid (mRNA) levels of Nrf2-responsive genes as well as Nqo1 protein and activity. BDL increased mRNA expression of multiple Nrf2 genes in mouse liver, compared to sham-operated controls. Follow-up studies investigating protein expression, enzyme activity, and Nrf2 dependency were limited to Nqo1. Nqo1 protein expression and activity in mouse livers was increased 2- to 3-, and 4- to 5-fold at 3 and 7 days after BDL, respectively. Studies also showed that BDL increases Nqol mRNA, protein expression, and enzyme activity in livers from wild-type mice, but not in Nrf2-null mice. In conclusion, expression of Nrf2 dependent genes is increased during cholestasis. These studies also demonstrate that Nqo1 expression and activity in mouse liver are induced via an Nrf2 dependent mechanism. PMID- 17278887 TI - Epithelial ovarian cancer and low malignant potential (LMP) tumors associated with a lower incidence of second primary breast cancer. AB - OBJECTIVES: Differences in the clinical characteristics of ovarian tumors of low malignant potential (LMP) and ovarian cancer have suggested divergences in tumor biology. The aim of this population-based study was to compare the risk of a second primary breast cancer after a history of either an LMP tumor or an epithelial ovarian cancer. METHODS: Breast cancers were evaluated among 3297 women with a history of LMP tumors, and 45,986 women with a history of epithelial ovarian cancer, within the Surveillance, Epidemiology, and End Results (SEER) Program. The expected incidence of breast cancer was then determined as a function of year, age, race, and geographic location, and combined with the observed incidence to derive the standardized incidence ratio (SIR). RESULTS: Forty-one (1.2%) patients with an LMP history were diagnosed with breast cancer, where 56.8 cases were expected, for an SIR of 0.72 [95% confidence interval (CI) 0.52-0.98]. Similarly, 734 patients (1.6%) with a history of ovarian cancer were diagnosed with breast cancer, where 809 were expected, for an SIR of 0.91 (95% CI 0.84-0.98). Overall, LMP patients were younger and had a shorter time between diagnoses. LMP patients also had a significantly lower relative risk of developing second primary breast cancers. CONCLUSION: Patients with a history of having either an LMP tumor or an epithelial ovarian cancer have a less than expected risk of subsequent breast cancer. Patients with LMP tumors are at lower risk than patients with a history of ovarian cancer for the development of these second malignancies. PMID- 17278886 TI - Induction of KLF4 in response to heat stress. AB - Kruppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger containing transcription factor with diverse regulatory functions in cell growth, proliferation, differentiation, and embryogenesis. However, little is known about the response of KLF4 to heat stress. In this study, Western blot and reverse transcriptase-polymerase chain reaction were performed to determine the changes in KLF4 expression in response to heat stress. The results showed that heat stress up-regulated KLF4 messenger RNA and protein levels in a time-dependent manner in vivo and in 4 cell lines. Moreover, a study with heat shock transcription factor 1 (Hsf1) gene knockout mice indicated that the induction of KLF4 in response to heat stress was mediated by Hsf1. This process occurred rapidly, indicating that KLF4 is an immediate early response gene of heat stress. Next, the roles of KLF4 under heat stress conditions were analyzed for cells overexpressing or deficient in KLF4. The results showed overexpression of KLF4 increased the death rate of C2C12 cells, whereas KLF4 deficiency decreased the injury of C2C12 cells from heat stress conditions, suggesting that KLF4 might play an important role in cell injury induced by heat stress. KLF4 might be an immediate early response gene and could play an important role in cell injury induced by heat stress. PMID- 17278888 TI - Is body mass index an independent risk factor of survival among patients with endometrial cancer? AB - OBJECTIVE: To evaluate whether body mass index (BMI) is an independent risk factor for survival in patients with endometrial adenocarcinoma. METHODS: Women treated for endometrial cancer at the State University of New York (SUNY), Downstate and Kings County Hospital between January 1982 and September 2003 were eligible. Patients were divided into groups based upon their histology at the time of diagnosis. The first included patients with low-grade endometrioid adenocarcinoma (FIGO grades 1 and 2); the second included grade 3 endometrioid adenocarcinoma; and the third contained papillary serous and clear cell carcinomas. Data regarding BMI, patient age, race, grade, and stage of disease and overall survival, were assessed by survival analysis, with P < 0.05 considered significant throughout. RESULTS: The analysis included 442 patients. Mean BMI was 32.6 +/- 8.2. There were 312 patients (70%) treated for low-grade endometrial adenocarcinoma; 64 patients (14%) for grade 3 endometrioid adenocarcinoma; and 71 patients (16%) for papillary serous and clear cell adenocarcinoma. Increased BMI was associated with improved overall survival (P = 0.003). BMI was also correlated to tumor grade, stage at diagnosis, age, and race. Tumor grade, stage, age, and race were correlated to survival. Statistical analyses revealed the majority of the association between BMI and survival can be attributed to the association between BMI and these other risk factors for survival in endometrial cancer. CONCLUSIONS: Increased BMI is associated with survival advantage among patients with endometrial cancer. Because of the relationship between obesity and other confounding variables obesity alone is not an independent predictor of survival. PMID- 17278885 TI - The stress protein gp96 is not an activator of resting rat bone marrow-derived dendritic cells, but is a costimulator and activator of CD3+ T cells. AB - Although low doses of tumor-derived stress protein gp96 elicit protective immunity to the tumor from which it is isolated, protection is lost at high doses because of the induction of immunoregulatory CD4+ T cells. This study evaluated the influence of gp96 on resting rat bone marrow-derived dendritic cells (BMDCs) and purified CD3+ T cells. In contrast to previous reports, gp96 had no effect on adhesion and costimulatory molecule expression by BMDCs, nor did it influence interleukin (IL)-10 and IL-12 secretion or their allostimulatory capacity. Gp96 did not bind to BMDCs but dose-dependently bound to CD4+ and CD8+ T cells. At low concentrations (1 and 25 microg/mL), gp96 acted as a costimulator of CD3+ T cells, inducing proliferation and the secretion of interferon (IFN)-gamma- and IL 10. Gp96 also increased the proliferation of CD28-costimulated CD3+ T cells and their secretion of IFN-gamma, IL-4, and IL-10. Gp96 had no effect at higher concentrations (50 and 100 microg/mL), despite the occurrence of cell surface binding at these concentrations. These findings indicate that gp96 can act as a costimulatory molecule for CD3+ T cells, and an observed increase in the IL-10: IFN-gamma secretion ratio induced by gp96 suggests that it might, at appropriate concentrations, promote a regulatory T-helper 2 (Th2)-like phenotype. PMID- 17278889 TI - FOLFOX-6 combination as the first-line treatment of locally advanced and/or metastatic pancreatic cancer. AB - OBJECTIVE: Advanced pancreatic carcinoma (APC) has a poor prognosis and chemotherapy remains the most common approach. Gemcitabine was the only drug recently approved for use as single agent therapy in APC. However, the combination of oxaliplatin and 5-fluorouracil (5-FU) has shown some promising results. This phase II trial was conducted to investigate the efficacy of oxaliplatin, 5-FU, and folinic acid (FOLFOX-6) in previously untreated APC patients. METHODS: We studied response rate, time to progression, and toxicity profile. Treatment included oxaliplatin 100 mg/m2 and folinic acid 400 mg/m2 on day 1 followed by a 5-FU bolus 400 mg/m2 and a 46-hour infusion of 3000 mg/m2 every 2 weeks. RESULTS: From January 2003 through December 2004, 30 eligible patients were included. Median age was 65 (range, 38-75). There were 22 patients who had metastatic disease and 29 had an adenocarcinoma. A total of 181 cycles were delivered with a mean of 6 cycles per patient. There were 23 patients evaluable for response. There were 8 patients with partial response (27.6% response rate) and 10 with stable disease status (34.5%), while tumor growth control was found in 62% of the patients. Recorded toxicities of grade 3/4 were: neutropenia (26.67%), thrombocytopenia and anemia (10% each), diarrhea (6.67%), and mucositis (3.33%). Neurosensory toxicity was mild. The median time to progression and the median survival were 4 and 7.5 months, respectively. CONCLUSION: In patients with APC, FOLFOX-6 regimen achieved an interesting response rate within a tolerable level of toxicity. This regimen seems to warrant further controlled investigation to confirm its efficacy. PMID- 17278890 TI - The role of adjuvant radiotherapy in microscopic tumor control after extrahepatic bile duct cancer surgery. AB - OBJECTIVES: To evaluate effects of radiotherapy (RT) after surgery for extrahepatic bile duct (EHBD) cancer. METHODS: There were 60 patients with EHBD cancer treated with postoperative RT. Surgical extents were R0 in 24 patients, R1 in 23, and R2 in 13. The indications for adjuvant RT were positive resection margin, lymph node metastasis, or more than pT2. Radiation was delivered to tumor bed and regional lymphatics, and for R1 or R2 patients, boost RT was planned. Overall survival (OS) and progression-free survival (PFS) was calculated and survival in the R0 and R1 patients with negative lymph nodes was compared. The pattern of treatment failures and prognostic factors were analyzed. RESULTS: The 2- and 5-year survival rates were 36.6% and 12.3% for OS, and 31.2% and 16.2% for PFS. In comparison of R0 with R1 patients who had negative lymph node, 2-year OS and PFS were 53.0% and 55.0% in R0, and 40.7% and 36.7% in R1 (P = ns). The first site of failure was loco-regional in 29 patients. The lymph node metastasis was a significant prognostic factor in OS (P = 0.04) and PFS (P = 0.02). CONCLUSIONS: Lymph node metastasis was a poor prognostic factor and adjuvant RT may be useful in patients with microscopic residual tumor. However, because there were high loco-regional recurrences, additional study is needed to determine more effective RT such as increased RT dose or use of radiosensitizers. PMID- 17278891 TI - A phase II trial of perifosine in locally advanced, unresectable, or metastatic pancreatic adenocarcinoma. AB - BACKGROUND: Perifosine, a heterocyclic alkylphosphocholine signal transduction inhibitor, has activity against multiple cell types in vitro. This is a phase II study to determine activity and toxicity of perifosine in pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma, performance status Eastern Cooperative Oncology Group 0 or 1, were enrolled. An oral loading dose of 900 mg was followed by 100 mg per day until progression or unacceptable toxicity. Response criteria in solid tumors (RECIST) methodology and a 2-stage design were used. Suspension could occur for inadequate response in the first cohort or for more than 25% grade 3 or greater toxicity. RESULTS: Ten patients were enrolled. Six received 1 month and 4 received 2 months of treatment. Four discontinued therapy as a result of progression and 2 because of clinical deterioration. Three died during treatment. One patient had stable disease but discontinued therapy as a result of unacceptable adverse events (95% confidence interval: 0.3-45%). There were no objective responses and all patients died of progressive disease. Median overall and progression-free survival was 1.85 months (95% confidence interval: 0.9-2.7) and 1.5 months (95% confidence interval: 0.9 1.9) respectively. CONCLUSION: The study was suspended and subsequently terminated as a result of unacceptable adverse events during the first stage. Perifosine does not appear to be worthy of further study in this group of patients. PMID- 17278892 TI - Imaging response in malignant glioma, RTOG 90-06. AB - OBJECTIVE: The purpose of this study was to determine if radiographic response correlates with survival for patients treated patients with malignant gliomas treated on Radiation Therapy Oncology Group (RTOG) protocol 90-06. This study compared patients treated with hyperfractionated radiation and 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) to standard fractionation and BCNU. METHODS: There were 453 patients evaluable. Histology included anaplastic astrocytoma (60) (AA), and glioblastoma multiforme (312) (GBM). All scans were forwarded to the RTOG central office and evaluated by a single reviewer without knowledge of outcome. Response at 4 months post initiation of therapy was evaluated by computed tomography or magnetic resonance image and compared with overall survival. RESULTS: For patients with no tumor on the 4 month scan the median survival was 20.3 months and the 2 year survival 43%. Patients with partial or minor response had a median survival of 18.1 and 14.2 months and 2 year survival of 37% and 29%. Patients with progression had a median survival of 8.6 months and 2 year survival of 10%. CONCLUSIONS: Response rates were similar in both arms. PMID- 17278893 TI - Simultaneous infield boost with helical tomotherapy for patients with 1 to 3 brain metastases. AB - OBJECTIVE: We sought to model the feasibility of a simultaneous in field boost (SIB) to individual brain metastases during a course of whole brain radiotherapy (WBXRT) using helical tomotherapy (HT) intensity-modulated radiation therapy. PATIENTS AND METHODS: Planning computed tomography data from 14 patients with 1 to 3 brain metastases were used to model an intralesional SIB delivery that yielded a total intralesional dose of 60 Gy with a surrounding whole brain dose of 30 Gy (designed to be isoeffective to WBXRT of 30 Gy with an 18 Gy in 1 fraction radiosurgery boost). Accuracy of treatment of a phantom on the HT unit was measured. Comparisons of HT delivery versus a conventional stereotactic radiotherapy technique for a particularly challenging simulated anatomy were made. RESULTS: In all cases, SIB to 60 Gy with WBXRT to 30 Gy was possible while maintaining critical structures below assigned dose limits. Estimated radiation delivery time for the SIB treatment was approximately 10 minutes per fraction. Planning and treatment of the head phantom was associated with an overall accuracy of 2 mm. Comparison to conventional noncoplanar arc fractionated stereotactic radiotherapy plan demonstrated similar target coverage and improved critical tissue sparing even for a challenging anatomy with multiple lesions in the same plane as the optic apparatus. CONCLUSIONS: Based on this study, use of an image guided SIB using HT seemed feasible and a phase I trial initiated at our institution is described. Potential advantages of this approach include frameless stereotaxis through daily megavoltage computed tomography localization, more efficient use of resources and exploitation of radiobiologic advantages of fractionation. PMID- 17278894 TI - Staging and monitoring of small cell lung cancer using [18F]fluoro-2-deoxy-D glucose-positron emission tomography (FDG-PET). AB - BACKGROUND: [18F]Fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan is widely used for the staging evaluation of nonsmall cell lung cancer, however, its use in small cell lung cancer (SCLC) remains investigational. PATIENT AND METHODS: We designed a prospective study to evaluate the role of PET in SCLC. Patients with SCLC underwent PET scanning as well as conventional imaging before and after treatment. RESULTS: A total of 39 PET scan examinations were performed in 21 patients with SCLC; 18 studies were performed before first-line chemotherapy and 21 studies were done during or after treatment. PET findings were compared with findings on CT scans of the chest or abdomen and bone scan. Discordant findings were detected in 14 out of 383 comparisons (4%) for 10 anatomic sites. In the thorax and the abdomen, PET agreed with CT scan in 92% to 100% of examinations assessing potential disease sites, including the contralateral chest, liver, and adrenals. PET agreed with bone scan in detecting bony lesions in 27 out of 32 imaging studies (84%): in 4 out of 5 discordant cases, PET findings were true and in 1 case indeterminate. Staging at baseline (limited, n = 6; extensive, n = 12) was identical when PET and sum of other staging procedures were compared. Response assessment was concordant between PET and CT scans in 8 of 9 patients who had evaluation before and after first-line chemotherapy. CONCLUSIONS: PET is potentially useful for the initial staging and monitoring of patients with SCLC and it may be superior to bone scan in detecting bone metastasis. The cost effectiveness of PET scan in SCLC remains to be determined. PMID- 17278895 TI - A phase I dose escalation study of weekly docetaxel and carboplatin in elderly patients with nonsmall cell lung cancer. AB - OBJECTIVE: We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD), and the safety profile of a weekly docetaxel and carboplatin combination regimen in the treatment of elderly patients with advanced nonsmall cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB and IV NSCLC, >70 years of age, performance status (ECOG) 0-2, with adequate bone marrow, renal, liver and cardiac function, were treated with docetaxel and carboplatin. Docetaxel was given at escalated doses starting from 20 mg/m2/wk on days 1, 8, and 15, with an increment of 5 mg/m2 followed by carboplatin also administered at escalated doses starting from AUC 4 to 6 (mg/ml/min); the regimen was administered every 4 weeks. The dose limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle. RESULTS: There were 25 patients enrolled in this study and assessed for safety. Neutropenia was the main DLT of the regimen; grade 3/4 neutropenia occurred in 5 patients (20%). Hematologic toxicities were mild, and included grade 3 thrombocytopenia in 1 patient (4%) and grade 3 anemia in 1 patient (4%). Nonhematologic toxicities were generally mild, and included grade 3 constipation in 1 patient (4%) and grade 3 renal disorder in 1 patient (4%). Objective responses were seen in 9 patients (response rate 36%). CONCLUSIONS: The MTD was carboplatin AUC 5 on day 1 and docetaxel 30 mg/m2 on days 1, 8, and 15; therefore, the RD for the phase II study is carboplatin AUC 5 and docetaxel 30 mg/m2. The combination of docetaxel and carboplatin is a feasible and well tolerated regimen for the treatment of elderly patients with advanced NSCLC. This regimen merits further investigation in phase II trials. PMID- 17278896 TI - Predicting changes in dose distribution to tumor and normal tissue when correcting for heterogeneity in radiotherapy for lung cancer. AB - PURPOSES: The purposes of this study were to examine dose alterations to gross tumor volume (GTV) and lung using heterogeneity corrections and to predict the magnitude of these changes. METHODS: Three separate conformal plans were generated for 37 patients with lung cancer: plan 1 corrected for heterogeneity, plan 2 did not correct for heterogeneity, and plan 3 used identical beams and monitor units from plan 2 but with heterogeneous calculations. Plans 1 and 2 were normalized to the 95% isodose line. Mean dose (MeanDGTV), maximum dose (MaxDGTV), and minimum dose (MinDGTV) to GTV and V20 were compared between plans 1 and 3. For each patient, the amount of lung in all beam paths of plan 3 was quantified by a density correction factor and correlated with the percent change. RESULTS: The median percent change in MeanDGTV, MaxDGTV, and MinDGTV between plan 3 and plan 1 was -4.7% (-0.1% to -19.1%, P < 0.0001), -5.59% (0.16% to -31.86%, P < 0.0001), and -4.88% (2.90% to -24.88%, P < 0.0001), respectively. The median V20 difference was -1% (1% to -8%). The density correction factor correlated with larger differences in MeanDGTV on univariate analysis. CONCLUSIONS: Heterogeneity correction lowers the dose to GTV by 5%. This difference can be correlated with the density correction factor. PMID- 17278897 TI - Predictive value of the preablation serum thyroglobulin level after thyroidectomy is combined with postablation 131I whole body scintigraphy for successful ablation in patients with differentiated thyroid carcinoma. AB - OBJECTIVES: To investigate the clinical importance of the combined use of serum thyroglobulin (Tg) levels measured just before ablation (ablation-Tg) and postablation 131I whole body scintigraphy (WBS) patterns for predicting ablation success in patients with differentiated thyroid carcinoma who received total thyroidectomy and 131I ablation therapy. METHODS: We retrospectively studied the early clinical outcomes for 81 differentiated thyroid carcinoma patients treated with total thyroidectomy and high-dose 131I ablation therapy between June 2001 and July 2004. RESULTS: Ablation success was achieved in 42 (97.7%) of the 43 patients with uptake in the thyroid bed only and ablation-Tg levels less than 10 ng/mL, whereas successful ablation was achieved in 9 (75.0%) of the 12 patients with uptake in the thyroid bed only and ablation-Tg levels equal to or greater than 10 ng/mL (P = 0.029). Among 15 patients with uptake including a lymph node and ablation-Tg levels less than 10 ng/mL, 14 patients (93.3%) showed ablation success, whereas successful ablation was achieved in only 2 (18.2%) of the 11 patients with uptake including a lymph node and ablation-Tg levels equal to or greater than 10 ng/mL (P < 0.001). CONCLUSIONS: These data indicate that the combined use of serum Tg levels measured just before ablation and the 131I WBS patterns after ablation may be an early predictor of ablation success in patients with differentiated thyroid carcinoma who received total thyroidectomy and high dose 131I ablation therapy. PMID- 17278898 TI - Is the Berg axillary lymph node categorization useful in the 3D environment? AB - OBJECTIVE: The Berg muscle-based categorization of axillary lymph node location (commonly referred to as levels I, II, and III) was used extensively by pathologists and surgeons to describe the extent of axillary node dissection in breast cancer patients. However, its reproducibility with different arm positions and utility in 3-dimensional radiation treatment planning hasn't been tested. METHODS: Computed tomography scans were observed in 16 patients in 2 positions: historical position (HP), ipsilateral arm abducted 90 degrees to the body axis; standard position (SP), arms above head. The volume, contents, and location of Berg lymph node levels (LNL) and the location of lymph nodes, surgical clips, pectoral muscles, and vascular structures relative to reference points were compared. RESULTS: From HP to SP there was no difference in LNL volumes. However, if measured from an anatomic landmark, the third thoracic vertebra (T3), LNL position varied: level I, an average of 23.1 mm anteriorly, P < 0.01; level II, 7.5 mm medially, P = 0.04; level III, 18.8 mm medially, P = 0.05. Using T3 as a reference: pectoralis major and minor muscles displaced medially (23.9 mm, P < 0.01 and 7.5 mm, P = 0.09) and anteriorly (18.2 mm, P < 0.01 and 11.2 mm, P < 0.01); axillary (18.0 mm, P < 0.01), subscapular (25.4 mm, P < 0.01), and lateral thoracic (8.4 mm, P < 0.01) vessels displaced anteriorly; axillary vessels displaced also medially (15.1 mm, P = 0.03). Disagreements in LN coverage with changes in arm position were observed in 60% (LNs) and 66% (clips) for level II. CONCLUSIONS: Surgeons, radiologists, and radiation oncologists should be aware that LNL coverage based on muscle boundaries varies significantly with arm position changes, making objective comparisons of information collected in different arm positions unreliable. PMID- 17278899 TI - A phase II study of second-line neoadjuvant chemotherapy with capecitabine and radiation therapy for anthracycline-resistant locally advanced breast cancer. AB - OBJECTIVE: According to data from Brazil's National Cancer Institute nearly 30% of the new patients who present with breast cancer have locally advanced disease. These patients are inoperable and tumor reduction is usually attempted with chemotherapy. First-line anthracyclin-based neoadjuvant chemotherapy is often effective; however, about 30% of the patients fail and to date there is no established second-line treatment. We have studied the concomitant use of radiation therapy and capecitabine in this setting, to determine the toxicity and efficacy of this regimen as a second-line neoadjuvant treatment. PATIENTS AND METHODS: Twenty-eight patients with inoperable locally advanced breast cancer refractory to first-line anthracycline based treatment were enrolled between January 2003 and May 2004. Patients received radiation therapy (total dose 5000 cGy) and concomitant capecitabine (850 mg/m2) twice daily for 14 days every 3 weeks. RESULTS: This treatment rendered 23 of the 28 patients (82%) operable. The 5 remaining patients did not undergo surgery because of disease progression. The median clinical tumor size decreased from 80 cm2 to 49 cm2. Microscopic residual disease was observed in 3 patients (13%) and another patient achieved a complete pathologic response. The median number of involved lymph nodes was 2 and treatment was well tolerated with no grade 3 or 4 events. CONCLUSION: Our data indicate that second-line neoadjuvant treatment with radiation therapy and capecitabine is feasible, well tolerated, and effective in patients with locally advanced breast cancer refractory to primary anthracycline-based treatment. These results suggest that a randomized study should be done to compare radiotherapy alone to capecitabine combined with radiotherapy. PMID- 17278900 TI - Neuroprotection during chemotherapy: a systematic review. AB - The development of neurotoxicity during antineoplastic therapy is one of the most common reasons for termination or modification of cancer treatment. A number of different agents have been proposed to provide neuroprotection without affecting antitumor efficacy. This review provides an evidence-based summary of neuroprotective medicines, an overview of the literature relating to neuroprotection during cancer treatment and a Neurologist perspective risk assessment and management. Through a systematic review the authors identified 49 papers published to date that report human clinical trials involving potential neuroprotectants in adults. Case reports and series completed in a prospective fashion were also included. Sensory neuropathies were the most prevalent subtype in the literature, and most were at least partially reversible with or without neuroprotective treatment. The majority of study medications had minimal side effects, though 2 trials were prematurely terminated because of adverse patient outcomes. No study reported an effect on antitumor efficacy. Because of the variability in study design, cancer type, outcome measures, and clinical confirmation of neuropathy, meta-analysis could not be appropriately performed. We highlight risk factors and discuss neuropathy screening. Descriptive analysis is provided which reveals that many of the agents studied were likely to confer some at least some neuroprotective benefit. PMID- 17278901 TI - Skin cancer of the head and neck with perineural invasion. AB - Perineural invasion occurs in 2% to 6% of cutaneous basal and squamous cell carcinomas of the head and neck and is associated with midface location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with perineural invasion appreciated on pathologic examination of the surgical specimen (incidental) or may present with cranial nerve deficits (clinical). The cranial nerves most commonly involved are the 5th and 7th nerves. Magnetic resonance imaging is obtained to detect and define the extent of perineural invasion; computed tomography is used to detect regional lymph node metastases. Patients with apparently resectable cancers undergo surgery usually followed by postoperative radiotherapy. Patients with incompletely resectable cancers are treated with definitive radiotherapy. The 5-year local control, cause specific survival, and overall survival rates are approximately 87%, 65%, and 50%, respectively, for patients with incidental perineural invasion compared with 55%, 59%, and 55%, respectively, for those with clinical perineural invasion. PMID- 17278902 TI - Placental site trophoblastic tumor and concomitant primary ovarian leiomyoma in a postmenopausal woman. PMID- 17278904 TI - Bibliography. Current world literature. Behavioural medicine. PMID- 17278903 TI - Recurrent gestational trophoblastic disease following persistently normal HCG titers: a rare occurrence. PMID- 17278905 TI - Schizophrenia research in the era of the genome, 2007. AB - PURPOSE OF REVIEW: The field of molecular genetics has now provided new technology to discover causes, mechanisms and targets for the development of treatments for even the complex inherited disorders, such as schizophrenia and other major psychiatric diseases. RECENT FINDINGS: As of the end of the year 2006, schizophrenia research has advanced a long way from epidemiological family surveys to examining the sequenced whole human genome. SUMMARY: Whether entering a new era of the genome will lead to prevention and/or cures will depend on our ability to make sense of the many positive and confusing findings that are now emerging, several of which will not stand the test of time. Going beyond genetic linkage and association studies to pathways, mechanisms and what changes gene expression will be the key. PMID- 17278906 TI - Migration and schizophrenia. AB - PURPOSE OF REVIEW: An exploration of the evidence that a history of migration is a risk factor for schizophrenia and an evaluation of those studies that seek an explanation for this. RECENT FINDINGS: A meta-analysis found an increased risk for schizophrenia among first-generation and second-generation migrants and found a particularly high risk for migrants from countries where the majority of the population was Black. The latter finding was confirmed and extended by a large first-contact incidence study in the UK, which found excessive risks for schizophrenia and mania in the African-Caribbean and black-African sections of the population. A very high risk of schizophrenia has also been reported for Moroccan males in the Netherlands. The explanation for these findings is uncertain. Social adversity, racial discrimination, family dysfunction, unemployment and poor housing conditions have been proposed as contributing factors. According to one hypothesis, the chronic experience of social defeat disturbs dopamine function in the brain. SUMMARY: A personal or family history of migration is a high risk factor for schizophrenia and there is now strong evidence against selective migration as the explanation. There is an increasing interest in the impact of social stressors on brain functioning and on the pathogenesis of schizophrenia. PMID- 17278907 TI - Cannabis and psychosis: an update on course and biological plausible mechanisms. AB - PURPOSE OF REVIEW: Cannabis use is the most commonly abused illicit substance. Its relation with psychosis remains a topic of debate. Epidemiological studies suggest that cannabis is a component cause accounting for approximately 10% of cases. An increasing number of studies have been published on neurobiological effects of cannabis and vulnerability of psychosis. RECENT FINDINGS: Acute cannabis administration can induce memory impairments, sometimes persisting months following abstinence. There is no evidence that residual effects on cognition remain after years of abstinence. The scarce literature on neuro imaging mainly done in nonpsychotic populations, show little evidence that cannabis has effects on brain anatomy. Acute effects of cannabis include increases of cerebral blood flow, whereas long-term effects of cannabis include attenuation of cerebral blood flow. In animals Delta9-tetrahydrocannabinol enhances dopaminergic neurotransmission in brain regions known to be implicated in psychosis. Studies in humans show that genetic vulnerability may add to increased risk of developing psychosis and cognitive impairments following cannabis consumption. Delta9-tetrahydrocannabinol induces psychotic like states and memory impairments in healthy volunteers. SUMMARY: Simultaneously with increasing understanding of neurobiological cannabis effects, there is a lack of studies in people with psychosis. There are plausible mechanisms that might explain the psychotogenic effects of cannabis. PMID- 17278908 TI - Effectiveness of early intervention in psychosis. AB - PURPOSE OF REVIEW: Over 15 years, early intervention in psychosis has grown to become a mainstream funded approach to clinical care. This review examines recent developments in evaluating the effectiveness of early intervention. It considers identification and treatment of those at risk of psychosis, as well as interventions in the post-onset phase of illness. RECENT FINDINGS: Development of methods identifying those at risk of psychosis continues to evolve. Promising results in the prevention and delay of transition to psychotic disorder from a high-risk state have been found. Psychological and psychosocial interventions are important components of these preventive programmes. Two recent meta-analyses indicate that there is a consistent relationship between duration of untreated psychosis and outcome independent of other factors. Further evidence shows that early intervention reduces the duration of untreated psychosis, produces better outcomes in terms of symptomatic and functional domains, and is cheaper than standard models of care. SUMMARY: There is evidence that early intervention is effective for early psychosis. Some challenges remain. These include developing a greater focus on functional recovery and prevention of relapse. PMID- 17278909 TI - Pharmacogenetics of antipsychotics: useful for the clinician? AB - PURPOSE OF REVIEW: The concept of individualized drug therapy on the basis of pharmacogenetics has become a central focus in psychopharmacology of schizophrenia. This article reviews recent advances in this field with respect to their importance for the clinician. RECENT FINDINGS: First, there is an increasing agreement about the importance of polymorphisms in cytochrome P450 enzymes and the effects of drug-drug interactions in relation to the incidence of adverse effects. Secondly, prediction of response on the basis of variants in candidate genes is incipient and remains elusive. Thirdly, some advances have been made in understanding the pharmacogenetics of weight gain. SUMMARY: Despite much effort, only a few of the results are now ready for translation into clinical practice. Cytochrome P450 genotyping would be a big step forward towards a more individualized drug treatment based on molecular diagnostics and could improve treatment, reduce adverse effects and increase compliance of the patients. Another promising field may be that of predicting the antipsychotic induced weight gain and it is hoped that commercially available DNA tests may be available within the next few years. Prediction of response is still hampered by many methodological and clinical problems and is not yet available to the clinician. PMID- 17278910 TI - Tardive dyskinesia: eliminated, forgotten, or overshadowed? AB - PURPOSE OF REVIEW: The present review focuses on atypical antipsychotics and tardive dyskinesia. RECENT FINDINGS: We have known for many years that clozapine has a diminished risk of tardive dyskinesia compared with typical antipsychotics. The last decade has seen the introduction of a number of other atypical antipsychotics, allowing us to begin evaluating whether they too share this attribute. In addition, the opportunity to use these drugs as first-line treatment permits a more precise means of establishing risk. While longer-term data are required, the limited evidence available clearly indicates that the atypical antipsychotics have a decreased liability of tardive dyskinesia, approximately 1% compared with 5% for typical agents annually. Like clozapine, the other atypical antipsychotics also demonstrate antidyskinetic properties in individuals with preexisting tardive dyskinesia. The underlying mechanisms remain unclear, and without such information it is not possible to say what clinical conditions, if any, might diminish or even eliminate these advantages. SUMMARY: An update is provided regarding the atypical antipsychotics and tardive dyskinesia. This information is critical in our decision-making regarding choice of antipsychotic and optimal use in the clinical setting. PMID- 17278911 TI - Sexual dysfunction in schizophrenia. AB - PURPOSE OF REVIEW: Sexual dysfunctions have been described as being common in schizophrenia patients. The pathophysiology behind their development remains unclear. They can be secondary to the disease itself or an adverse event of antipsychotic medication. Therapeutic interventions are also not well studied. RECENT FINDINGS: Earlier work has suggested that second-generation antipsychotics bear fewer risks for developing sexual dysfunction because of a lower propensity to elevate prolactin levels, although the latter does not apply to amisulpride and risperidone. Only a few controlled trials with larger patient samples have been performed in the past. SUMMARY: The review covers studies published from March 2005 to June 2006 focusing on sexual dysfunctions in schizophrenia patients, as well as their possible causes. Treatment options and the impact of sexual dysfunction on quality of life are also covered. The reviewed papers show no clear consistency regarding potential advantages of one drug over another. Many trials suffer from small sample sizes. The field badly needs more and larger studies on this topic. PMID- 17278912 TI - Are somatoform disorders 'mental disorders'? A contribution to the current debate. AB - PURPOSE OF REVIEW: During the last 2 years, a debate has started over whether the somatoform symptoms/medically unexplained symptoms are wrongly placed under the category of mental disorders (section F in International classification of diseases-10 and in Diagnostic and statistical manual for mental disorders-IV). RECENT FINDINGS: Most experts on medically unexplained symptoms agree that there is a substantial need for revision of the diagnoses of somatoform disorders. While some authors suggest moving the somatoform disorders from axis I to axis III, others suggest improving the classification of these syndromes on axis I, such as by using empirically derived criteria and by introducing psychological descriptors which justify the categorization as a mental disorder. In contrast to the situation when the last version of Diagnostic and statistical manual for mental disorders was published, new empirical data has shown some psychological and behavioural characteristics of patients with somatoform symptoms. These and other empirically founded approaches can be landmarks for the revision of this section in Diagnostic and statistical manual for mental disorders-V and International classification of diseases-11. SUMMARY: The classification of somatoform disorders as 'mental disorders' could be justified if empirically founded psychological and behavioural characteristics are included into the classification process. Attention focusing, symptom catastrophizing, and symptom expectation are outlined as possible examples of involved psychological processes. PMID- 17278913 TI - Psychosocial and behavioral aspects of cardiovascular disease prevention in men and women. AB - PURPOSE OF REVIEW: Cardiovascular disease is a serious threat to population health. The true causes are not fully known, but a number of biological and behavioral risk factors have been identified. In this review we aim at understanding psychosocial, behavioral and lifestyle factors and their role in clinical care of patients with cardiovascular disease. We describe recent scientific evidence of psychosocial and life style risk and behavioral interventions to reduce risk in cardiovascular disease. We also discuss whether intervention programs are effective against cardiovascular disease and its risk factors, and whether they are of benefit to the patients. Gender aspects and ethnic variations are highlighted. RECENT FINDINGS: In recent European Guidelines of CVD Prevention in Clinical Practice, behavioral factors have become recognized to be true risk factors and identified as important barriers to lifestyle change for patients with cardiovascular disease. Lifestyle changes play a pivotal role in clinical prevention of cardiovascular disease, as they are recommended as the first choice of intervention modalities before pharmacological treatment is initiated. SUMMARY: While there is now common agreement about the importance of psychosocial risk factors for cardiovascular disease, a better consensus about intervention methods is needed in order to evaluate and appreciate the future scientific evidence from behavioral cardiovascular preventive efforts. PMID- 17278914 TI - Psychosocial and behavioral interventions for chronic medical conditions. AB - PURPOSE OF REVIEW: This paper critically reviews recent studies that have used behavioral or psychosocial interventions aimed at preventing type 2 diabetes mellitus, cardiovascular disease and HIV/AIDS as well as the psychosocial management of cardiovascular disease, HIV and cancer. RECENT FINDINGS: Behavioral (lifestyle) interventions can decrease risk of type 2 diabetes mellitus and cardiovascular disease. Psychosocial interventions have proven efficacy for alleviating distress in patients medically treated for cancer, cardiovascular disease and HIV/AIDS. These interventions may also help to prevent HIV infection, and improve medication adherence in HIV/AIDS. SUMMARY: Behavioral and psychosocial interventions are useful in preventing some chronic diseases and for alleviating distress in patients who have been medically treated for diseases such as cancer, cardiovascular disease and HIV/AIDS. Findings regarding the effects of psychosocial interventions on disease processes, morbidity and mortality are not yet well established and require appropriate clinical trials. PMID- 17278915 TI - Neuroendocrine mechanisms of stress and social interaction: implications for mental disorders. AB - PURPOSE OF REVIEW: The purpose of the present review is to consider further evidence for the role of neuroendocrine mechanisms in mental disorders by focusing on recent trends and advances in the field of psychoneuroendocrinology. RECENT FINDINGS: Recent studies confirm the importance of the hypothalamic pituitary-adrenal axis for the development and course of mental disorders. Notably, the neuropeptide oxytocin has been shown to reduce the responsiveness of the hypothalamic-pituitary-adrenal axis to social stress and to improve social approach behavior. A better understanding of the neuroendocrine mechanisms of action underlying normal behavior has recently been translated to studies investigating novel therapeutic approaches using hormone administration. SUMMARY: Neuroendocrine systems relevant to behavior clearly demonstrate their impact for the field of psychiatry. Further neuroendocrine research provides insight into the origins of mental disorders both from an etiological perspective and an interventional perspective. PMID- 17278916 TI - The role of illness perceptions in patients with medical conditions. AB - PURPOSE OF REVIEW: In this article we summarize recent investigations into the influence of illness perceptions on outcomes in patients with medical conditions. RECENT FINDINGS: Developments in assessment include the publishing of a new brief scale to assess illness perceptions and the examination of the relationship between patient drawings of their illness and outcomes. Recent studies in primary care highlight the importance of patients' beliefs and emotional responses to their illness as being important in influencing their satisfaction with the consultation, reassurance following negative medical testing and future healthcare use. Recent research shows illness perceptions to have associations with a number of outcomes in chronic illness including self-management behaviours and quality of life. As yet, however, few interventions have been developed designed to change illness perceptions and improve illness outcomes. Emerging areas of research include the application of illness perceptions to mental illness and genetic and risk factor testing. SUMMARY: Research on illness perceptions has confirmed that patients' beliefs are associated with important outcomes in a broadening range of illnesses and risk factor testing. New interventions based on this model have the potential to improve patient outcomes but have yet to be widely developed and applied. PMID- 17278918 TI - Bibliography. Current world literature. Schizophrenia. PMID- 17278917 TI - Psychosomatic obstetrics and gynecology--a neglected field? AB - PURPOSE OF REVIEW: The purpose of the review was to evaluate recent studies in the field of psychosomatic obstetrics and gynecology for new directions in research. RECENT FINDINGS: Psychosomatic obstetrics and gynecology covers a wide canvas, and the present review shows extensive research in some areas and large gaps in others. There have been significant developments in the field of pregnancy-related psychiatric morbidity, particularly anxiety states and posttraumatic stress disorder; however, there is a need for better and more specific measurement and screening methods. Among gynecological conditions there have been advances in research on chronic pelvic pain and gynecological cancers, but most other gynecological conditions have been neglected. What is encouraging is the increasing amount of research from the developing world and the focus on common reproductive conditions based on community studies. In addition, in light of the recent findings and concerns related to hormone replacement therapy, research on mood disorders related to menopause is increasing, with refinement in measurements, definitions, and treatment methods. SUMMARY: While studies on prevalence and risk factors abound, what is missing are well conducted intervention studies. The next phase of research should focus on preventive and intervention studies that are easily adaptable the world over. PMID- 17278920 TI - Work disability in rheumatic diseases. AB - PURPOSE OF REVIEW: To review developments in the literature concerning work disability in the rheumatic diseases. RECENT FINDINGS: There have been three sets of studies to emerge in the last year. In the first, several studies analyze alternative research methods to document work disability. The second set uses qualitative methods to identify the specific factors that affect the decision to leave work. The third set analyzes interventions to reduce work disability. SUMMARY: The quantitative and qualitative studies concur on the importance of flexible working conditions as an important, if not the most important risk factor for work disability in a diverse array of rheumatic diseases. PMID- 17278921 TI - Health literacy and arthritis research and practice. AB - PURPOSE OF REVIEW: The following review summarizes contributions from rheumatology to the growing field of health literacy. RECENT FINDINGS: Arthritis related publications have primarily contributed to one strand of research in health literacy: assessments of print materials and considerations of the match between the reading grade level of materials and the reading skills of intended audiences. Unlike researchers addressing other chronic diseases such as diabetes, however, researchers and practitioners in rheumatology have yet to examine links between patients' literacy skills and health outcomes. In addition, only one early study reports on evaluation findings of an education program designed for audiences with low literacy skills. No other studies report on efforts to increase health literacy in arthritis, reduce the demands of print materials for education or research purposes, or on efforts to ameliorate the effects of limited literacy skills among patients. SUMMARY: Health literacy may well influence arthritis outcomes as well as recruitment efforts in arthritis research. The 2004 report on health literacy from the Institute of Medicine calls for additional studies focused on the links between health literacy and health outcomes. PMID- 17278922 TI - Outcomes in rheumatoid arthritis: incorporating the patient perspective. AB - PURPOSE OF REVIEW: As biologics have improved the prognosis for rheumatoid arthritis, the prioritization of outcomes has shifted. Methods of quantifying concerns of particular importance to patients as a basis for better addressing the patient perspective in treatment are being developed. This review aims first to highlight some of the recent research in more traditional outcomes and then to focus on the rapid development of patient-centered outcomes over the last several years. RECENT FINDINGS: Clinical trials with combinations of biologics and other disease-modifying antirheumatic drugs have reported significant improvement in radiographs, inflammatory markers and joint exams in rheumatoid arthritis patients. Concomitantly, several studies have appeared in major journals, reporting that patients are emphasizing outcomes such as fatigue, return to normalcy and mental health that are less easily measured by the traditional outcomes markers. SUMMARY: Recent studies have shown both that rheumatologist and patient approaches to achieving wellness differ and providing patients with a sense of control in reaching that state of wellness leads to better outcomes. Current research is focused on evaluating how best to measure the patient assessments and incorporate the patient voice into the clinic. PMID- 17278923 TI - Advances in arthroscopic surgery: indications and outcomes. AB - PURPOSE OF REVIEW: To examine recent trends in the use of arthroscopic surgical techniques to address musculoskeletal problems. The review is particularly timely given the rapidly expanding range of indications for diagnostic and therapeutic arthroscopic procedures involving virtually every peripheral joint. RECENT FINDINGS: We focus on arthroscopic approaches to problems of the hip, wrist, elbow and ankle. Hip arthroscopy is permitting novel, minimally invasive approaches to the management of femoral acetabular impingement, labral tears, loose bodies and chondral lesions. Wrist arthroscopy has provided novel approaches to ligament tears, synovitis and fractures. Ankle arthroscopy has been especially helpful with soft tissue impingement syndromes, synovitis and fracture. Elbow arthroscopy has been especially helpful in the management of synovitis and osteoarthritis due to osteophytosis. Complications of arthroscopic procedures occur very rarely. Virtually all the literature on arthroscopy outcomes comes from small uncontrolled studies. SUMMARY: Arthroscopy provides a safe alternative to arthrotomy in the management of a wide range of clinical problems. The generally weak designs of studies performed to date compromises the strength of recommendations that can be made about the role of these procedures in clinical practice. PMID- 17278924 TI - Fibromyalgia treatment update. AB - PURPOSE OF REVIEW: Fibromyalgia is a common chronic pain disorder characterized by complex symptomatology and few consistently effective treatments. The purpose of this review is to highlight the recent literature from April 2005 through September 2006 involving treatment options. RECENT FINDINGS: Prior evidence suggests that medication and self-management approaches to care can improve symptoms, function and well-being in this patient population. Recent studies examining the efficacy of two serotonin and norepinephrine-reuptake inhibitors- duloxetine and milnacipran--and the anticonvulsant pregabalin are encouraging. Studies evaluating different forms of exercise continue to support the belief that increased physical activity is an essential component of any treatment plan for the patient with fibromyalgia. Three studies added to the understanding of treatment adherence. Finally, three studies evaluating the efficacy of acupuncture in the treatment of fibromyalgia showed conflicting results, but added to the knowledge needed for clinicians to have substantive conversations with patients. SUMMARY: Recent studies support the recommendation of a multimodal approach to treatment involving individualized, evidence-based pharmacotherapy and self-management. Treatment goals should include the improvement of symptoms, primarily pain and sleep, and the promotion of positive health behaviors with the aim of improving physical function and emotional well-being. PMID- 17278925 TI - Epidemiology and health services: year in review. AB - PURPOSE OF REVIEW: Epidemiology began as the study of the occurrence of disease in populations. Initial studies focused on the presence of diseases by person, place, and time to identify risk factors for disease. The field has grown to include many subfields recognizing the contributions of multiple factors to disease susceptibility. RECENT FINDINGS: This review will focus on articles published October 2005-November 2006 relevant to genetic epidemiology, pharmacoepidemiology, and social determinants of health and health disparities. SUMMARY: Genetic epidemiology is the study of genetic contributions to disease occurrence, and of population-based genetic risks for disease. Genetics influences not only susceptibility to disease, but also the phenotype and severity of disease. Pharmacoepidemiology examines the outcomes of medication use, including clinical benefits and adverse effects. Gene-environment interactions are also included in this area. Typical topics in pharmacoepidemiology include studies of medication use, risks, benefits and genetic factors influencing the metabolism of medications. Social epidemiology is the study of social determinants of health, including psychosocial behaviors, socioeconomic status, interactions of individuals, the collective health of the community in which a person lives, and the position of the individual within society. Social epidemiology is directly relevant to studies of socioeconomic and ethnic disparities. PMID- 17278926 TI - Therapeutic advances in gout. AB - PURPOSE OF REVIEW: The purpose of this review is to highlight the recent developments in the management of gout. RECENT FINDINGS: Guidelines for the diagnosis and management of gout from EULAR, quality of care indicators, and outcome measures for clinical trials have been published. The standards of gout diagnosis and management are very low. Allopurinol remains the mainstay for serum uric acid lowering therapy. In an important percentage of patients receiving allopurinol, serum uric acid levels are insufficient to promote crystal dissolution. Febuxostat, a new serum uric acid lowering drug, has shown good results. Information on uricase continues to appear. For treatment of gouty inflammation, etoricoxib (a new cyclooxygenase 2 inhibitor) has been shown to be as effective as indomethacin. Finally, the association of gout with the metabolic syndrome and its comorbidities, and the newly described association of gout with myocardial infarction, bring lifestyle and dietary modifications to the front in the management of gout. SUMMARY: Proper gout management requires changes to the physician's attitude towards the disease; essentially: (1) an unequivocal diagnosis based in urate crystal identification, (2) a clearly settled aim of the treatment: crystal elimination from the joints and elsewhere, and (3) proper use of the available therapeutic alternatives. Promoting a proper lifestyle appears to be especially important. PMID- 17278927 TI - Imaging modalities and monitoring measures of gout. AB - PURPOSE OF REVIEW: Imaging modalities for gout have been mostly restrained to radiographs. Ultrasonography, computed tomography and magnetic resonance imaging are emerging techniques that could be used for diagnosis, evaluation, and monitoring acute and chronic gout. RECENT FINDINGS: Diagnosis of gout is based on urate crystal observation with microscopy. Recently, crystal deposition in the hyaline cartilage has been described to be different in gout from that of calcium pyrophosphate, but validation of the findings is pending. Severity of gout with simple radiographs may not disclose periarticular or intra-articular urate deposition. Ultrasonography, computed tomography and magnetic resonance imaging may improve the evaluation of tophi not apparent in clinical examination or simple radiographs. Monitoring urate deposition may be accomplished with imaging techniques. This would be of outstanding interest for clinical trials, but also for evaluating clinical response to urate-lowering therapy. Although preliminary results evaluating for validity and reliability have been very recently reported for magnetic resonance imaging, computed tomography and ultrasonography, sensitivity to change studies are still pending. Also, monitoring of chronic inflammation with imaging techniques, such as power-Doppler, deserve further studies. SUMMARY: Evidence exists regarding the usefulness of imaging techniques for diagnosis, evaluation of severity, and monitoring of gout, but further investigation is needed. PMID- 17278928 TI - Genetics and experimental models of crystal-induced arthritis. Lessons learned from mice and men: is it crystal clear? AB - PURPOSE OF REVIEW: We examine the major genes in mice and humans involved in the pathogenesis of monosodium urate, calcium pyrophosphate dihydrate and hydroxyapatite crystal-induced arthritis. RECENT FINDINGS: Several genetic causes of renal disease associated with hyperuricemia and gout provide insight into genes involved in renal urate handling. Mutations or polymorphisms in exons 4 and 5 and intron 4 of urate transporter 1 may be independent genetic markers of hyperuricemia and gout. Genetic analysis supports the role of ANKH mutations in calcium pyrophosphate dihydrate-induced arthritis. ANKH gain-of-function mutations were confirmed by functional studies; however, the crystals formed in ATD5 cells were basic calcium phosphate, not calcium pyrophosphate dihydrate, underlying the significance of chondrocyte differentiation state and the factors regulating normal and pathological mineralization. Animal models have implicated a general model of crystal-induced inflammation involving innate immunity through the NALP3 (Natch domain, leucine-rich repeat, and PYD-containing protein 3) inflammasome signaling through the interleukin-1 receptor and its signaling protein myeloid differentiation primary response protein 88. SUMMARY: Genetic analysis has elucidated genes responsible for crystal formation and animal models have unveiled mechanisms in the development of crystal-induced arthritis. Future studies will hasten understanding of the pathology of crystal-induced arthritis and provide new therapies. PMID- 17278929 TI - Recent advances in crystal-induced acute inflammation. AB - PURPOSE OF REVIEW: The aim of this article is to highlight recent advances suggesting essential involvement of the innate immune system in crystal-induced acute inflammation. RECENT FINDINGS: Gout is a disease caused by the deposition of monosodium urate monohydrate crystals. Precise mechanisms underlying the initiation of monosodium urate monohydrate crystal-induced acute inflammation, however, are not known. Recent investigations provided novel evidence in the pathology of acute gout. Immunological study indicated that monosodium urate monohydrate crystals can act as a 'danger signal' that resembles exogenous adjuvants. Two laboratories have documented interesting findings that Toll-like receptor-mediated pathways or MyD88-dependent pathways are involved in monosodium urate monohydrate crystal-induced acute inflammation. Upregulation of the triggering receptor expressed on myeloid cells 1 (TREM-1) in phagocytes by the stimulation with monosodium urate monohydrate crystals has been demonstrated. Furthermore, pathological significance of NALP 3 inflammasome in gout has been shown. These findings provide a new concept that the innate immune system may play a crucial role on the triggering of crystal-induced acute inflammation. Spontaneous resolution is a characteristic feature of acute gout. Involvement of nuclear hormone receptors, peroxisome proliferator-activated receptor gamma and liver X receptor alpha, during the termination of acute gout has been also shown. SUMMARY: These studies provided a new insight into the mechanisms underlying the initiation and the termination of monosodium urate monohydrate crystal-induced acute inflammation. PMID- 17278930 TI - New insights into renal transport of urate. AB - PURPOSE OF REVIEW: This review focuses on recent progress in the understanding of various aspects of renal transport of urate. RECENT FINDINGS: Since the molecular cloning of the renal apical urate/anion exchanger URAT1 (SLC22A12), several membrane proteins relevant to the transport of urate have been identified. The molecular identification of two sodium-coupled monocarboxylate transporters, SMCT1(SLC5A8) and SMCT2(SLC5A12), and the emerging role of PDZ (PSD-95, DglA, and ZO-1) scaffold for renal apical transporters have led to a new concept of renal urate transport: urate-transporting multimolecular complex, or 'urate transportsome', that may form an ultimate functional unit including the sodium coupled urate transport system by linking URAT1 and sodium-coupled monocarboxylate transporters or the coordinated apical urate uptake system by balancing reabsorptive (URAT1) and efflux (NPT1/OATv1 and MRP4) transporters. In addition, genetic variations of the URAT1 gene are associated not only with idiopathic renal hypouricemia but also with reduced renal urate excretion. SUMMARY: Although our knowledge of renal urate handling has been increased by the molecular identification of urate transport proteins and by results of genetic studies on patients with serum urate disorders, current evidence is insufficient to fully understand the precise mechanism governing the bi-directional transport of urate. Further studies are still necessary. PMID- 17278931 TI - Update in calcium deposition diseases. AB - PURPOSE OF REVIEW: Calcium pyrophosphate dihydrate and basic calcium phosphate crystals are common components of osteoarthritic synovial fluids and define subsets of patients with inflammatory or rapidly destructive arthritis. Recent literature concerning clinical and etiologic aspects of calcium pyrophosphate dihydrate and basic calcium phosphate crystal arthritis are reviewed. RECENT FINDINGS: Recent literature reminds us of the propensity of calcium pyrophosphate dihydrate deposition disease to mimic other syndromes affecting the elderly. Several new studies reinforce the prevalence and significance of extra-articular calcium pyrophosphate dihydrate deposits, and demonstrate the presence of basic calcium phosphate-like whitlockite crystals in intervertebral discs. Current work serves to increase our appreciation for the complex role of the putative pyrophosphate transporter, ANKH, in healthy and diseased cartilage. The application of newer radiographic techniques to the diagnosis of calcium pyrophosphate dihydrate deposition disease holds promise for easier and more accurate identification of these crystal deposits in vivo. Work demonstrating the efficacy of a crystal poison in an animal model of osteoarthritis provides good evidence for a pathogenic role of calcium crystals in osteoarthritis, and hope for new therapies for these diseases. SUMMARY: Continued work will further our understanding of these common crystals and their associated clinical syndromes. PMID- 17278932 TI - Cross cultural aspects of rehabilitation in rheumatic diseases. AB - PURPOSE OF REVIEW: The aim of this article is to describe progress in the understanding of the relationship between culture, race, ethnicity and similar factors as they pertain to rehabilitation and the rheumatic diseases. This review highlights important current issues and indicates areas for future study. RECENT FINDINGS: There is very little published research in this area of rehabilitation medicine. Recent findings and observations indicate that there are many important cultural aspects of rehabilitation in the rheumatic diseases with several societal as well as individual implications. This is a rapidly growing area of work as it is being increasingly recognized that an understanding of these cross cultural issues is essential in order to be able to ensure the delivery of clinically and cost effective rehabilitation services which are client centred and consequently culturally appropriate. Although the interrelationship of culture, race, genetics, ethnicity, language, religion, history, geography, socioeconomic status and educational level is complex, studies are beginning to reveal the contributions of these factors to ensuring minimization of disability and high quality rehabilitation strategies. SUMMARY: Although much neglected, the importance of cultural aspects of rehabilitation in rheumatic diseases is being increasingly recognized and understood. Issues that have been identified include the rehabilitation needs assessment of different ethnic groups, the development of culturally valid outcome measures and the implementation and evaluation of culturally competent multidisciplinary rehabilitation programs. PMID- 17278933 TI - Pool exercise for individuals with fibromyalgia. AB - PURPOSE OF REVIEW: The benefits of general aerobic exercise for individuals with fibromyalgia have been established. Recently, there have been a number of randomized controlled trials that evaluate the benefits of pool exercise for fibromyalgia. This review will integrate the results of eight pool exercise studies that have been published in the last 7 years. RECENT FINDINGS: Pool exercise has been evaluated against sedentary control groups, land-based exercise and immersion in a warm, mineralized pool. Pool exercise has been shown to be as effective as land-based exercise and may have greater benefits with respect to mood and sleep duration. Based on follow-up studies, exercise-induced improvements in physical function, pain and mood may persist for up to 2 years. Pool exercise may be better tolerated as an initial means of exercise by individuals with arthritis in weight-bearing joints (because of water buoyancy) or by individuals who fear exercise will exacerbate their pain. SUMMARY: Pool exercise can be an effective intervention for individuals with fibromyalgia. Future studies should reassess subjects at multiple time points to determine the time course of exercise-induced improvements and further explore the effects of pool exercise on mood and sleep quality. PMID- 17278934 TI - People with arthritis and their families in rehabilitation, care and research. AB - PURPOSE OF REVIEW: People with arthritis play major roles in treatment and research. This review summarises the current knowledge on tools for enhancing shared-decision making in arthritis care; individual and family involvement in rehabilitation; and the consumer's role in arthritis research. RECENT FINDINGS: There are discrepancies in the use of appropriate arthritis treatment. To facilitate evidence-informed treatment choices, a number of decision aids have been developed. A recent systematic review concluded that decision aids could improve the shared-decision making process in a variety of diseases; but only one clinical trial was found on a musculoskeletal condition (back surgery). The evidence on family member participation in arthritis education programs is mixed, partly due to a lack of content specifically targeting family members in some studies. Finally, people with arthritis are playing important roles as collaborators in research. Early experience indicates a mutually beneficial relationship for both the individual and researchers. SUMMARY: This review offers three recommendations: First, further clinical trials are needed to test the effectiveness of decision aids in arthritis management. Second, education programs involving strong social support training for family members may improve client outcomes. Third, we encourage further studies to examine the experiences and challenges of people living with arthritis when participating as research partners. PMID- 17278935 TI - Hand osteoarthritis--an increasing need for treatment and rehabilitation. AB - PURPOSE OF REVIEW: This review describes advances in our knowledge on the clinical burden of hand osteoarthritis, its relation to radiographic signs of osteoarthritis and potential targets for therapy. Treatments and trial methodology for hand osteoarthritis are critically reviewed. RECENT FINDINGS: Recent studies have shown that there is an association between radiographic hand osteoarthritis and hand pain, and that symptomatic hand osteoarthritis leads to substantial disability. Some risk factors for hand osteoarthritis have been described but the development of hand osteoarthritis is still unclear. Unfortunately, pharmacological therapies for hand osteoarthritis are lacking and have been investigated little. Only a few studies on other treatment modalities are available. Surgical treatments are not covered in this review. SUMMARY: Advances have been made in our understanding of symptomatic hand osteoarthritis. Potential targets for therapy are recognized. The challenge for the coming years is to conduct clinical trials of high quality in hand osteoarthritis. PMID- 17278936 TI - The International Classification of Functioning, Disability and Health in practice in rheumatological care and research. AB - PURPOSE OF REVIEW: The aim of this article is to review the recent literature on the use of the International Classification of Functioning, Disability and Health (ICF) in practice in rheumatological care and research. The specific aims were to explore how the ICF has been used as a frame of reference for identifying functional problems of patients using qualitative and quantitative research methods; determining typical problem areas of functioning; and measuring functioning of people with rheumatic diseases. RECENT FINDINGS: The ICF was used as a frame of reference for formulating interview questions and for analysing data in qualitative research. The majority of experiences of patients could be linked to the ICF. In quantitative surveys and by reviewing medical records, the ICF could be used as a model to identify problem areas of patients from the perspective of experts. The ICF served as a frame of reference for performing content comparisons of several health-status instruments. SUMMARY: In rheumatological care and research, the translation of aspects of functioning important to patients and of the content of health-status instruments to ICF terms enables researchers and clinicians to condense and compare the meaning of patients' experiences and the content of the instruments. PMID- 17278937 TI - Cardiovascular risk factors, fitness and physical activity in rheumatic diseases. AB - PURPOSE OF REVIEW: There is increased recognition of an excess risk of cardiovascular disease in patients with rheumatic disorders. Physical inactivity is a frequent complication of arthritis, and also common in the general population. In this review, we highlight recent findings on risk factors for cardiovascular disease in patients with rheumatic diseases, and explore the role of physical activity for the prevention of cardiovascular disease. RECENT FINDINGS: Inflammatory mechanisms are clearly involved in cardiovascular disease in patients with systemic lupus erythematosus and rheumatoid arthritis. In rheumatoid arthritis, disability is also a major predictor of cardiovascular disease. A sedentary lifestyle increases the risk of cardiovascular disease in the general population, and high physical activity prevents cardiovascular disease mortality and morbidity. Successful treatment of rheumatic disease with control of inflammation and improved functional capacity may also reduce the risk of cardiovascular disease. SUMMARY: As part of the effort to prevent vascular comorbidity, regular exercise should be encouraged in patients with rheumatic diseases, and structured interventions to reduce adverse lifestyle factors scientifically evaluated. PMID- 17278938 TI - The role of exercise in the rehabilitation of patients with systemic lupus erythematosus and patients with primary Sjogren's syndrome. AB - PURPOSE OF REVIEW: The purpose of this review is to present an update on the evidence-based effects of exercise in systemic lupus erythematosus and in primary Sjogren's syndrome. RECENT FINDINGS: Physical capacity is reduced in both systemic lupus erythematosus and primary Sjogren's syndrome and fatigue is a dominating and disabling symptom in both conditions. The documentation on the effect of exercise on the rehabilitation of patients with systemic lupus erythematosus and primary Sjogren's syndrome is sparse; the studies are few and the sample sizes often small. The available studies indicate that patients with systemic lupus erythematosus of mild to moderate disease activity as well as patients with primary Sjogren's syndrome benefit from exercise of moderate to high intensity. Positive effects can be expected with regard to aerobic capacity, fatigue, physical function and depression. SUMMARY: There is reason to believe that exercise should be included in the rehabilitation of patients with mild to moderate systemic lupus erythematosus and patients with primary Sjogren's syndrome. Further research is needed and should aim to evaluate the effect of exercise on groups with varying degree of disease severity and to document the long-term impact on the disease. PMID- 17278939 TI - Bibliography. Current world literature. Epidemiology and health-related services. PMID- 17278940 TI - Is it safe for lupus patients to take estrogen? It depends .... PMID- 17278941 TI - Racial/ethnic differences in the use of complementary and alternative medicine in patients with arthritis. AB - OBJECTIVE: To examine use of complementary and alternative medicine (CAM) by individuals with osteoarthritis (OA) from 4 ethnic groups, differences in CAM use among groups, and correlates of CAM use. METHODS: Data were obtained from individuals from 4 ethnic groups (African, Asian, and Hispanic Americans, and Caucasians) participating in trials assessing celecoxib efficacy. A questionnaire assessing CAMs specifically used to help arthritis was administered at screening. Use of 42 specific therapies within 7 categories-alternative medical systems, mind-body interventions, manipulation and body-based methods, energy therapies, and 3 types of biologically based therapies--was queried. RESULTS: More than 80% of subjects reported that they used some CAM for arthritis in the past month. In contrast, 50% reported the use of prescription medicines, and 52% reported the use of over-the-counter medicines. Dietary practices were the most common type of CAM (71.5%), followed by mind-body interventions (42.4%), topical agents (38.1%), use of supplements or herbs (32.9%), and manipulation and body-based methods (21.4%). African Americans were more likely to report any CAM use than other groups (89.1% versus 83.1% [Asian], 81.1% [Hispanic], 77.7% [Caucasian]). African and Asian Americans more commonly reported the use of mind-body interventions in general, and prayer in particular. African Americans were also most likely to report the use of topical agents. Asian Americans were most likely to report use of alternative medical systems, manipulation methods, and supplements. Caucasians were least likely to report use of dietary practices. CONCLUSION: Individuals with OA commonly use CAM. Use of these therapies varies by racial/ethnic group. Some CAMs may be effective for symptom relief, while others may interact with prescription medications, suggesting that routine queries by physicians concerning CAM use would be beneficial. PMID- 17278943 TI - Reduced pain of intraarticular hyaluronate injection with the reciprocating procedure device. AB - BACKGROUND: Greater than 50% of patients report significant pain with intraarticular injection of hyaluronate. The reciprocating procedure device (RPD), also known the reciprocating syringe, has 2 plungers that reciprocate with each other, permitting one-handed operation. The RPD increases physician control of the needle and is proposed to reduce patient pain during syringe procedures. OBJECTIVES: To determine in a randomized controlled trial whether the RPD induces less pain than the traditional syringe during intraarticular hyaluronate therapy for the knee. METHODS: Eighty intraarticular injection procedures of the knee were randomized to either the conventional syringe or the RPD using hyaluronate sodium derivative (Hylan G-F-20). Outcome measures included physician's estimate of pain, patient pain (Visual Analogue Pain Scale [VAPS]), procedure duration, operator satisfaction, complications, and response to the injected medication. RESULTS: Patients reported 85% more pain than physicians estimated. Fifty-one percent (19/37) of subjects experienced moderate to severe pain with the conventional syringe, while only 14% (6/43) experienced pain with the RPD. The RPD reduced pain scores (RPD VAPS score: 2.12 +/- 2.15; conventional syringe VAPS score: 4.22 +/- 3.25; P < 0.001), reduced procedure time (RPD: 1.34 +/- 1.09, conventional syringe: 1.90 +/- 1.35 minutes, P < 0.001), and improved physician satisfaction (RPD VASS Score: 9.02 +/- 0.80, conventional syringe 5.69 +/- 1.33, P < 0.001). CONCLUSIONS: Patients have considerably more pain with intraarticular needle introduction and injectable hyaluronate therapy than physicians estimate. The RPD reduces patient pain, reduces procedure time, and improves needle introduction compared with the conventional syringe for hyaluronate injection therapy for the knee. PMID- 17278942 TI - Are overweight and obese adults with arthritis being advised to lose weight? AB - BACKGROUND: Obesity is a risk factor for the development and progression of arthritis. Weight loss can provide symptomatic benefit for adults with arthritis. OBJECTIVE: To describe the proportion and characteristics of adults with self reported diagnosed arthritis who report ever having been advised by a doctor or health professional that losing weight might benefit their arthritis or joint symptoms and to assess whether receiving the advice was associated with trying to lose weight. METHODS: Using population-based survey data from the 2005 Behavioral Risk Factor Surveillance Survey (BRFSS), we classified respondents according to their arthritis status, gender, ethnicity, age, education, body mass index, activity limitations due to joint symptoms, whether or not they received advice to lose weight from a doctor or health professionals, and whether they report trying to lose weight. RESULTS: Less than half (45.7%) of overweight or obese respondents with arthritis reported ever being advised by a doctor or health professional that losing weight might help their arthritis or joint symptoms. Respondents who were more likely to have received the advice were female, older, obese, with higher levels of education, and reported activity limitations due to joint symptoms. Overweight and obese respondents who reported receiving advice to lose weight were significantly more likely to report trying to lose weight than those who did not receive advice (odds ratio [OR] = 3.75; 95% confidence interval [95% CI] = 3.39-4.15). CONCLUSIONS: Receiving advice was associated with a greater likelihood of trying to lose weight. Health care professionals should advise overweight and obese adults with arthritis about the potential benefits of weight loss and should provide the resources to assist these patients in losing weight. PMID- 17278944 TI - Is osteoporosis generalized or localized to central skeleton in ankylosing spondylitis? AB - BACKGROUND: Osteoporosis at the lumbar spine and at the femur is a well established complication in ankylosing spondylitis (AS), but the exact mechanism and the distribution of osteoporosis are not known absolutely. OBJECTIVE: To determine whether the osteoporosis is generalized or localized to central skeleton and to examine the relation between bone mineral density (BMD) and disease activity and radiologic progression in patients with AS. METHODS: In this study, 26 patients with AS and 33 healthy controls matched for age and sex were recruited to the study. Hip and forearm BMD were measured by dual energy X-ray absorptiometry (DEXA). Laboratory and clinical disease activity parameters were documented, and anteroposterior sacroiliac radiographs were taken to determine the radiologic progression. RESULTS: The urine deoxypyridinoline levels of the patients with AS were statistically significantly higher (P = 0.02) and the serum osteocalcin levels were significantly lower with respect to controls (P = 0.03). The femoral neck and femur BMD values and T scores were significantly lower in patients with AS compared with the controls (P = 0.019, 0.003, 0.01, and 0.01, respectively). The differences in BMD values and T scores of the distal 1/3 radius between 2 groups were not statistically significant. The relation between BMD and disease activity, and radiologic progression in patients with AS could not detected. CONCLUSION: Sparing of distal regions such as the as radius suggests that osteoporosis might be due to localized effects of inflammatory activity or immobility rather than a systemic effect. Both increased resorption and decreased formation might be involved in the pathogenesis of osteoporosis. Radius BMD may not be appropriate to evaluate bone loss in patients with AS. PMID- 17278945 TI - Recurrent Henoch-Schonlein purpura in children. AB - BACKGROUND: Henoch-Schonlein purpura (HSP), also known as anaphylactoid purpura is a clinically recognizable systemic disorder occurring in children, mainly from ages 3 to 10 years. OBJECTIVES: To describe the clinical, epidemiological, and laboratory findings in a group of patients with recurrent HSP, admitted to a tertiary pediatric center. METHODS: Retrospective analysis of medical records of patients hospitalized due to HSP between 1969 and 2004. RESULTS: Two hundred sixty children (56.7% males) were hospitalized due to HSP, 7 (2.7%) more than once. There were no statistically significant differences in demographic or clinical characteristics between the patients with 1 event of HSP and patients with recurrence. Mean age of the subgroup with recurrence was 3.67 years (10 months to 7.4 years) at the first episode, and 5.03 years (2.2-10 years) at the second one, with a mean lag period of 13.5 +/- 2.8 months (range 2-26). The duration of the recurrent clinical symptoms ranged from 9 to 30 days, and in 72% of those patients, resolution took more than 14 days. CONCLUSION: In our inpatient population, no clinical or laboratory characteristics were found to be predictive of recurrence; the second episode was longer than the first and the lag period between the 2 episodes was substantially longer than previously reported. Hospital admissions for recurrent HSP are not common. Nevertheless, a good prognosis was the rule of our admitted patients. PMID- 17278946 TI - New onset systemic lupus erythematosus in a transgender man: possible role of feminizing sex hormones. AB - Systemic lupus erythematosus (SLE) is rare in men, and significantly more common in women. Sex hormone influences are believed to a play a role in these gender differences. We present the unusual case of a transgender man who had been taking feminizing sex hormones, who later developed new onset SLE with cardiorespiratory and renal involvement. While not definitive, this case raises intriguing possibilities on the relationship between the use of feminizing sex hormones and the development of SLE. PMID- 17278947 TI - What does it take to diagnose Behcet disease? AB - Behcet disease is a systemic inflammatory disease of unknown etiology initially described as a triad of recurrent oral ulcers, genital ulcers, and hypopyon uveitis affecting young male adults. Internationally agreed diagnostic criteria have been proposed to assist in the diagnosis. We present the case of a 26-year old African-American male who presented with right brachial plexopathy due to axillary aneurysm. Further evaluation revealed the presence of a common carotid artery aneurysm, superior vena cava, and left subclavian vein thrombosis. A few months later, he developed severe bilateral panuveitis with hypopyon, retinal vasculitis, and optic nerve inflammation. Although our patient had no recollection of oral or genital ulcers, the constellation of deep vein thrombosis, multiple arterial aneurysms, bilateral panuveitis, positive pathergy skin test, and elevated inflammatory markers led to the working diagnosis of Behcet disease. Arterial involvement occurs in 3%-5% of patients with Behcet disease and may manifest as either true or false aneurysms. Deep vein thrombosis is the most common venous manifestation and involvement of venae cavae and their tributaries is not uncommon. Anterior and posterior uveitis and retinal vasculitis not only have a prognostic value in Behcet disease but in this particular case supported the diagnosis. In conclusion, incomplete forms of Behcet vasculitis exist and clinicians should be alert to atypical presentations of the disease. PMID- 17278948 TI - Localized striated muscle vasculitis in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is one of the most prevalent connective tissue diseases and can be complicated by vasculitis with systemic manifestations. Rheumatoid vasculitis can range in severity from a widespread, life-threatening disease refractory to treatment to a more benign, localized disease responsive to treatment. We describe here a patient with RA who presented with bilateral calf muscle pain secondary to rheumatoid vasculitis. The patient had intractable calf muscle pain which did not respond to nonsteroidal anti-inflammatory drugs and muscle relaxants. He did not have any other manifestations of rheumatoid vasculitis such as skin ulcers, peripheral neuropathy, or gastrointestinal involvement. A thorough diagnostic work-up concluding with a muscle biopsy revealed a non-necrotizing small vessel vasculitis. The patient's symptoms responded very well to a course of steroids and he required no additional cytotoxic agents. This case illustrates that rheumatoid vasculitis can present as an isolated striated muscle vasculitis characterized by a relatively benign course and prompt resolution with the initiation of steroids. Clinicians need to be aware that such a phenomenon can exist to facilitate early recognition and appropriate treatment. PMID- 17278949 TI - Familial Mediterranean fever successfully treated with etanercept. AB - Colchicine is the only drug known to effectively prevent familial Mediterranean fever (FMF) attacks, as well as FMF-associated amyloidosis. Unfortunately, colchicine is neither always effective nor always well tolerated, leaving some patients and their physicians with inadequate weaponry to fight this hazardous disease. We present a patient with recurrent episodes of abdominal, scrotal, and joint attacks, who was diagnosed with FMF and advised to take colchicine. Diarrhea prevented optimal treatment with this drug and led to a trial of etanercept, with resolution of FMF manifestations. This case adds to a growing body of evidence suggesting that tumor necrosis factor (TNF) blockade may result in resolution and prevention of further FMF attacks. PMID- 17278950 TI - An unusual cause of a neck mass. PMID- 17278952 TI - Basic science for the clinician 42: handling the corpses: apoptosis, necrosis, nucleosomes and (quite possibly) the immunopathogenesis of SLE. AB - Death happens. It is, in essence, part of life. Humans deal with death in a variety of different ways, but often by keeping it at arms' length. At the cellular level, there are many forms of death, part of the development of organs and tissues (apoptosis) and part of pathologic processes (necrosis). The former, as has been described in an earlier paper in this series, is designed to eliminate the corpse with no evidence that it was ever there. Clearance is usually swift and effective, avoiding inflammation and specific immune interventions or responses. However, there is gathering evidence that autoimmunity leading to systemic lupus erythematosus may be due to ineffective or improper clearance of apoptotic debris, making it proinflammatory and allowing it to become highly immunogenic. This formulation also suggests therapeutic options that have already been demonstrated effective in controlling models of human autoimmune disease. This article reviews some aspects of this theory and some of the molecular biologic features of necrosis, apoptosis, and other forms of cell death. PMID- 17278953 TI - Tattoo: inflicted vasculitis? PMID- 17278954 TI - A patient with polymyositis and normal serum creatine kinase level. PMID- 17278955 TI - Modafinil treatment for fatigue associated with fibromyalgia. PMID- 17278956 TI - Primary antiphospholipid antibody syndrome: how certain can you be of the diagnosis? PMID- 17278957 TI - Failure of etanercept to control extra-articular manifestations of rheumatoid arthritis. PMID- 17278958 TI - Reversible posterior leukoencephalopathy in systemic lupus erythematosus with thrombotic thrombocytopenic purpura. PMID- 17278960 TI - The GNB3 C825T polymorphism and essential hypertension: a meta-analysis of 34 studies including 14,094 cases and 17,760 controls. AB - OBJECTIVES: The C825T single nucleotide polymorphism of the G-protein beta3 (GNB3) has been implicated in susceptibility to essential hypertension, through the expression of an alternatively spliced truncated variant. In an effort to clarify earlier inconclusive results, we performed a meta-analysis of population based case-control genetic association studies. METHODS: Random-effects methods were applied on summary data in order to combine the results of the individual studies. RESULTS: We identified in total 34 studies, including 14,094 hypertensive cases and 17,760 controls. The TT versus CC + CT contrast yielded an overall odds ratio (OR) of 1.08 [95% confidence interval (CI): 1.01, 1.15], the contrast of TT + CT versus CC, an OR of 1.17 (95% CI: 1.06, 1.29), whereas that of the T allele versus C allele yielded a non-significant OR of 1.05 (95% CI: 0.98, 1.13). There was moderate evidence for a publication bias in the latter two contrasts, which was eliminated after excluding studies not in Hardy-Weinberg equilibrium and those performed on non-normal populations (those with a diagnosis of diabetes, obesity and myocardial infarction). Subgroup analyses revealed that non-significant estimates arose from studies on Asian populations, as opposed to the Caucasian ones. Furthermore, the frequency of the T allele was lower in Caucasians and these populations were found to inhabit higher latitudes. CONCLUSIONS: The findings are in agreement with a recently proposed causal model for systolic blood pressure, which correlates it with the T allele and the absolute latitude. Further studies are needed in order to fully address questions about the aetiological mechanism of the particular association, as well as to study the effect in populations of African descent. PMID- 17278961 TI - Climate not cultivars in the NO-ing of red wines. PMID- 17278962 TI - Are minor gene effects of clinical importance? PMID- 17278963 TI - Slowing arterial aging: how far have we progressed? PMID- 17278964 TI - Alterations in pulse wave velocity and augmentation index in Australian aboriginals: characteristics and mechanisms. PMID- 17278965 TI - Added VALUE of an ancillary study on ambulatory blood pressure monitoring. PMID- 17278966 TI - Incidence and predictors of hypertension over 8 years among Chinese men and women. AB - OBJECTIVE: To determine the 8-year incidence of hypertension and its risk factors among Chinese adults. METHODS: A population-based sample of 10,525 Chinese adults aged > or = 40 years and free from hypertension at baseline was followed up from 1991 to 1999-2000. Incident hypertension was defined as systolic pressure > or = 140 mmHg, diastolic pressure > or = 90 mmHg, or current use of antihypertensive medication. RESULTS: Over a mean of 8.2 years of follow-up, 28.9% of men and 26.9% of women developed hypertension. Among men, independent predictors of incident hypertension were baseline age [relative risk (RR) per 5 years: 1.10; 95% confidence interval (CI): 1.07, 1.13], living in urban regions versus rural regions (RR: 0.74; 95% CI: 0.64, 0.85), alcohol drinking versus non-drinking (RR: 1.13; 95% CI: 1.02, 1.24), prehypertension versus normotension (RR: 1.70; 95% CI: 1.53, 1.88), heart rate (RR of third versus first tertile: 1.27; 95% CI: 1.13, 1.44), body mass index (RR of third versus first tertile: 1.28; 95% CI: 1.12, 1.46) and low versus high physical activity (RR: 1.27; 95% CI: 1.10, 1.47). Results were similar for women, with current smoking in place of alcohol drinking and opposite results for region. The population-attributable risk of modifiable risk factors was between 25 and 50%. CONCLUSIONS: These data indicate that the incidence of hypertension is high among these Chinese adults, and suggest that 25 50% of new hypertension cases could be prevented with risk factor modification. Given the excess cardiovascular mortality associated with hypertension, these data call for urgent improvements in hypertension prevention and control programs in China. PMID- 17278967 TI - Job strain in men, but not in women, predicts a significant rise in blood pressure after 6.5 years of follow-up. AB - BACKGROUND: Job strain (high demands and low decision latitude) has been associated with hypertension and cardiovascular disease, especially in men. Most studies on job strain and hypertension have been cross-sectional, and prospective data are inconsistent. OBJECTIVE: To prospectively describe the effects of different psychosocial work characteristics on office blood pressure changes. METHODS: In total, 448 men and women, mean age 55 years, were followed for a mean of 6.5 years. At baseline, work characteristics and cardiovascular risk factors were assessed. Only employed subjects aged 63 years or younger were eligible for participation. RESULTS: Men with baseline job strain had a significantly greater increase in both systolic blood pressure (7.7 mmHg, P = 0.02), and diastolic blood pressure (5.6 mmHg, P = 0.003), compared to the group with low work demands and high decision latitude ('relaxed'). These findings were significant also after adjustments for age, follow-up time, baseline blood pressure, blood pressure treatment at baseline and follow-up, and length of education. Work demands were more strongly correlated with blood pressure increase than decision latitude. For women, no significant associations between psychosocial work characteristics and blood pressure changes were found, apart from a weak trend of association between increasing decision latitude and increasing blood pressure. CONCLUSION: Job strain significantly predicts an increase in office blood pressure in middle-aged men, but not in women. Work demands were more strongly correlated with blood pressure increase than decision latitude in men. PMID- 17278968 TI - Maternal nutrition during gestation and carotid arterial compliance in the adult offspring: the Dutch famine birth cohort. AB - OBJECTIVE: Experimental evidence indicates that maternal undernutrition during gestation may program hypertension in the offspring. We investigated whether maternal undernutrition leads to increased arterial stiffness. METHODS: We measured carotid artery lumen diameter (LD), distensibility (DC), stiffness (beta), and compliance (CC) by M-mode ultrasound in 673 individuals, aged 56-61 years, who had been born as term singletons around the time of the 1944-45 Dutch famine. RESULTS: Maternal famine exposure had no effect on any of the measures of carotid size or stiffness in the offspring. Low maternal weight at the end of pregnancy and low birth weight were associated with decreased LD (0.01 mm/kg maternal weight, sex-adjusted P < 0.001; 0.1 mm/kg birth weight, sex-adjusted P = 0.08) and CC (0.002 mm2/kPa per kg maternal weight, sex-adjusted P = 0.001; 0.03 mm2/kPa per kg birth weight, sex-adjusted P = 0.03), but neither was associated with increased beta, or decreased DC. These effects were not attenuated by adjusting for maternal protein/carbohydrate ratio in the third trimester. The association of low birth weight with increased CC diminished after adjusting for maternal weight. The association of maternal weight with CC was smaller when adjusted for LD. CONCLUSION: Our findings suggest that small maternal size, not poor maternal diet, in late gestation programs decreased arterial compliance in the adult offspring by affecting vessel size rather than vessel wall stiffness. PMID- 17278969 TI - Activation of endothelial nitric oxide synthase by red wine polyphenols: impact of grape cultivars, growing area and the vinification process. AB - OBJECTIVE: Accumulating data document protective effects of red wine in cardiovascular disease by improved nitric oxide bioavailability. Not all wines, however, seem to be equally effective. The aim of the present study was to elucidate the impact of grape cultivars, growing area and the vinification/fermentation process on the ability of red wine polyphenol extracts to increase human endothelial nitric oxide synthase (eNOS) promotor and enzyme activity. METHODS: We produced polyphenol extracts from a variety of red wines from all over the world and tested their influence on eNOS promotor activity by a luciferase reporter gene assay. Selected extracts were subjected to the L arginine-L-citrulline conversion assay to confirm that enhanced eNOS transcription results in enhanced enzyme activity. RESULTS: We show that polyphenol extracts from wines of specific origin and grape cultivars vary strongly in their individual activity. However, when averaged, the activity could not be attributed to a specific grape cultivar or growing area. Resveratrol alone significantly enhanced eNOS promotor and enzyme activity, although at concentrations higher than those available in effective concentrations of red wine polyphenol extracts. Extracts of grape juice showed activity as well. CONCLUSIONS: The biological activity of red wines on eNOS transcription depends neither on grape cultivars nor on growing area in general. Resveratrol may be the most promising ingredient in red wine polyphenol extracts, but does not account for the complete effect. A large part of the active components are genuine grape compounds, since extracts of grape juice that did not undergo a fermentation process also showed activity. PMID- 17278970 TI - The Pl(A1/A2) polymorphism of glycoprotein IIIa and cerebrovascular events in hypertension: increased risk of ischemic stroke in high-risk patients. AB - OBJECTIVE: The platelet GPIIIa plays a pivotal role in platelet aggregation. Previous studies showed an association between the GPIIIa Pl(A1/A2) polymorphism and coronary thrombosis, while there is only contrasting evidence about its role in stroke. We explored the possibility that this polymorphism represents a risk factor for stroke in hypertensive patients. METHODS: We studied two populations. In loco, we genotyped 140 hypertensive control individuals and 28 hypertensive patients with ischemic stroke. Furthermore, we performed an analysis of previously published data of 451 Sardinian hypertensive patients, already characterized and genotyped. RESULTS: Association analysis revealed that the Pl(A2) distribution was similar between hypertensive patients with and without stroke, but when considering a more homogeneous population of high-risk hypertensive patients, defined according to ESH/ESC 2003 guidelines, we observed that the frequency of the Pl(A2) allele was higher among stroke versus nonstroke patients (stroke, 46.4%; nonstroke, 22.6%; P = 0.01). The multiple regression analysis taking into account this polymorphism among other factors known to contribute to ischemic stroke confirmed the Pl(A2) allele as an additive risk factor for stroke (B = 0.986, Wald = 4.943, P < 0.03), increasing the risk of stroke by 2.9 (95% confidence interval = 1.23-6.85, P < 0.02). Similar results were obtained in the Sardinian population: in hypertensive patients with three or more risk factors, Pl(A2) increases the risk (odds ratio = 2.8, 95% confidence interval = 1.3-6.0, P < 0.001) and is an additive risk factor for stroke (B = 1.073, Wald = 6.920, P < 0.01). CONCLUSIONS: Our data suggest that the Pl(A2) polymorphism is a genetic determinant of ischemic stroke in a selected high-risk hypertensive population. PMID- 17278971 TI - SAH gene variants are associated with obesity-related hypertension in Caucasians: the PEGASE Study. AB - OBJECTIVE: The SAH gene locus has recently been proposed to be involved in obesity-related hypertension in Japanese individuals. METHODS: To replicate independently the initial findings in another ethnic group, we scanned the entire SAH gene in 190 Caucasian chromosomes. A total of 651 patients with essential hypertension and 776 controls (PEGASE Study) were genotyped for all identified variants using allele-specific oligonucleotides, and single nucleotide polymorphism as well as haplotype analyses were carried out. We also performed transient transfection experiments, northern and western blots, immunoprecipitation, and acyl-coenzyme A synthetase activity assays. RESULTS: We identified five polymorphisms in the promoter region (C-1808T, G-1606A, 962ins/del, G-451A, T-67C), two in introns 5 and 7 (T+9/In5C, A+20/In7T), and one missense variant (K359N). Carriage of the -1606A allele was significantly associated with hypertension [odds ratio (OR) 1.28, P = 0.049] as was 359N (OR 1.35, P = 0.048) compared with non-carriers. Conversely, for -962del, the OR for hypertension was 0.80 (P = 0.042). The SAH alleles -1606A and 359N, but not 962ins/del, displayed a raising effect on body mass index (BMI; P = 0.004 and P = 0.030, respectively) in hypertensive as well as in control individuals. After adjustment for BMI in hypertensive individuals, only the OR associated with 962ins/del remained significant (OR 0.77, P = 0.028). Functional analyses in BHK did not reveal differences for SAH 359N or 359K-containing constructs, formally excluding K359N as the functional variant. CONCLUSION: We confirm recent evidence that the SAH locus is associated with obesity-related hypertension, in which pathophysiological context SAH variants affecting blood pressure remain, however, to be shown. PMID- 17278972 TI - Heritability of blood pressure traits and the genetic contribution to blood pressure variance explained by four blood-pressure-related genes. AB - OBJECTIVE: To study the heritability of four blood pressure traits and the proportion of variance explained by four blood-pressure-related genes. METHODS: All participants are members of an extended pedigree from a Dutch genetically isolated population. Heritability and genetic correlations of systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure were assessed using a variance components approach (SOLAR). Polymorphisms of the alpha-adducin (ADD1), angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R) and G protein beta3 (GNB3) genes were typed. RESULTS: Heritability estimates were significant for all four blood pressure traits, ranging between 0.24 and 0.37. Genetic correlations between systolic blood pressure, diastolic blood pressure and mean arterial pressure were high (0.93-0.98), and those between pulse pressure and diastolic blood pressure were low (0.05). The ADD1 polymorphism explained 0.3% of the variance of pulse pressure (P = 0.07), and the polymorphism of GNB3 explained 0.4% of the variance of systolic blood pressure (P = 0.02), 0.2% of mean arterial pressure (P = 0.05) and 0.3% of pulse pressure (P = 0.06). CONCLUSION: Genetic factors contribute to a substantial proportion of blood pressure variance. In this study, the effect of polymorphisms of ADD1, AGT, AT1R and GNB3 explained a very small proportion of the heritability of blood pressure traits. As new genes associated with blood pressure are localized in the future, their effect on blood pressure variance should be calculated. PMID- 17278973 TI - Small artery elasticity assessed by pulse wave analysis is no measure of endothelial dysfunction. AB - OBJECTIVES: Determination of endothelial function has emerged as a crucial factor in the assessment of individual cardiovascular risk. Sonographic measurement of flow-mediated dilation (FMD) is the most widespread technique to assess endothelial function, but analysis is very time-consuming and requires an experienced examiner. Recently, it was speculated that a reduction of small artery compliance (C2) measured by pulse wave analysis might be an indicator of endothelial dysfunction. In the present study, we investigated the correlation of pulse wave analysis parameters and endothelial function with special regard to patients who are at increased risk for endothelial dysfunction. METHODS: One hundred and thirty-six subjects (65 male, 71 female) were included in the study. One hundred and twenty-three probands were hypertensive. Endothelium-dependent vasodilation was assessed sonographically (flow-mediated dilation) using standard protocols and as a change of reflection index (deltaRI) after application of salbutamol by photoplethysmography. Small artery compliance, large artery compliance (C1), and systemic vascular resistance (SVR) were measured by computerized pulse wave analysis of the radial artery (CR-2000; Hypertension Diagnostics, Eagan, Minnesota, USA) and were tested for correlation with FMD. RESULTS: Mean FMD was 6.29 +/- 2.86%. Means of pulse wave analysis-derived vascular parameters were 4.91 +/- 2.86 ml/mmHg x 100 (C2), 13.35 +/- 5.41 ml/mmHg x 10 (C1) and 1611.6 +/- 348.5 dynes x s x cm(-5) (SVR). Regression analysis excluded a significant correlation between FMD, C2, C1 and SVR (r2 < 0.05 each) both in hypertensives and normotensives. There was no significant correlation between C2 and deltaRI (r2 = 0.023). CONCLUSION: Our findings show that static measurement of vascular parameters by an automated pulse-wave analysis procedure cannot be used to assess endothelial function. Further studies are needed to examine whether a dynamic measurement of arterial compliance before and after stimulation of the endothelium (e.g. by ischemia) might quantify endothelial dilatory capacity in a better way. PMID- 17278975 TI - Increased arterial stiffness in remote Indigenous Australians with high risk of cardiovascular disease. AB - OBJECTIVE: To assess central and peripheral arterial stiffness in Indigenous and European Australians with and without type 2 diabetes using applanation tonometry to obtain the augmentation index (AI) and pulse wave velocity (PWV). METHODS: AI was assessed in 162 Indigenous Australians (60 with type 2 diabetes) participating in a population-based study and 121 Australians of European ancestry (38 with diabetes) of similar age and sex. PWV was assessed in a subgroup: n = 62 indigenous, n = 118 European participants. RESULTS: The indigenous group had higher AI than the European group [mean (SD) 32 (12) versus 24 (12)%, P < 0.0001] and carotid-femoral PWV [8.4 (1.8) versus 7.1 (2.2) ms(-1), P < 0.0001]. There were no significant differences between groups regarding blood pressure and total cholesterol; however, indigenous individuals had higher fasting glucose, insulin, haemoglobin A1c, triglycerides, waist circumference (despite lower body mass index), and a higher prevalence of cigarette smoking. Fifty-five per cent of the variance in AI was explained on multiple regression analysis by age, sex, indigenous participant, heart rate, mean arterial pressure, height, triglycerides and waist circumference. Age, indigenous participant, heart rate, mean arterial pressure and antihypertensive medication explained 56% of the variance in PWV. Variables of the metabolic syndrome and smoking, C-reactive protein (CRP), homocysteine and heart rate clustered with indigenous status on factor analysis. CONCLUSIONS: Indigenous Australians have higher indices of peripheral and central arterial stiffness than European Australians of similar age and sex. Factor analysis revealed that metabolic syndrome variables, smoking, CRP, homocysteine and heart rate clustered with 'indigenous participant' and may explain increased arterial stiffness in this group. PMID- 17278974 TI - Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. AB - OBJECTIVES: Arterial stiffening and endothelial dysfunction are hallmarks of aging, and advanced glycation endproducts (AGE) may contribute to these changes. We tested the hypothesis that AGE crosslink breakers enhance endothelial flow mediated dilation (FMD) in humans and examined the potential mechanisms for this effect. METHODS: Thirteen adults (nine men, aged 65 +/- 2 years) with isolated systolic hypertension (systolic blood pressure > 140 mmHg, diastolic blood pressure < 90 mmHg or pulse pressure > 60 mmHg) on stable antihypertensive therapy were studied. Subjects received placebo (2 weeks) then oral alagebrium (ALT-711; 210 mg twice a day for 8 weeks). Subjects and data analyses were blinded to treatment. Arterial stiffness was assessed by carotid augmentation index (AI) and brachial artery distensibility (ArtD) using applanation tonometry and Doppler echo, and endothelial function by brachial FMD. Serum markers of collagen metabolism and vascular inflammation were assessed. RESULTS: Alagebrium reduced carotid AI by 37% (P = 0.007) and augmented pressure (16.4 +/- 10 to 9.6 +/- 9 mmHg; P < 0.001). Heart rate, arterial pressures, and ArtD, were unchanged. FMD increased from 4.6 +/- 1.1 to 7.1 +/- 1.1% with alagebrium (P < 0.05), and was unrelated to altered shear stress or regional arterial distensibility. However, FMD change was inversely related to markers of collagen synthesis, p selectin and intracellular cell adhesion molecule (all P < 0.05). Alagebrium associated changes in plasma nitrite plus nitrate was inversely correlated with plasma matrix metalloproteinase 9 and type I collagen (P = 0.007). CONCLUSIONS: Alagebrium enhances peripheral artery endothelial function and improves overall impedance matching. Improved endothelial function correlates better with reduced vascular fibrosis and inflammation markers than with vessel distensibility. AGE crosslink breakers may reduce cardiovascular risk in older adults by reduced central arterial stiffness and vascular remodeling. PMID- 17278976 TI - Relationship between arterial distensibility and coronary atherosclerosis in angina patients. AB - OBJECTIVE: Arterial stiffening is associated with an increased risk of cardiovascular disease. However, limited evidence exists on whether it also relates to subclinical atherosclerosis, thereby providing a non-invasive marker of the overall cardiovascular status. The aim of the present study was to provide information on arterial stiffening in angina patients in whom angiographic evaluation allowed quantification of coronary atherosclerosis. METHODS: We studied 101 patients with angina from a large number admitted to our hospital for coronary angiography. In each patient, radial (RA), subdiaphragmatic aorta (AO) and carotid (CA) distensibility (Dist) were measured by an ultrasonic device, following ultrasonic exclusion of atherosclerotic lesions at these specific sites. Patients were classified into three groups according to the angiographic findings: (i) no significant coronary lesions (lumen obstruction < 50%, group A); (ii) one (group B); and (iii) two or three (group C) coronary vessels with hemodynamic significant plaques (lumen obstruction > 50%). RESULTS: Age, male prevalence, previous cardiovascular disease and interventions were progressively greater or more common from group A to C, whereas several other risk factors (plasma glucose, serum cholesterol, smoking, history of hypertension, etc.) did not differ between the three groups or between the group with single vessel (B) versus the group with multivessel disease (C). CA and AO Dist decreased progressively from group A to C with a significant relationship in the group as a whole between distensibility values and the number of diseased vessels. The progressive decrease in AO Dist from group A to C remained significant after adjustment for variables that showed between-group differences (such as gender, age and systolic blood pressure) and the ROC curve showed it to be a more sensitive and specific marker of coronary atherosclerosis than CA Dist. RA Dist was similar in the three groups and showed no relationship with the number of diseased vessels in the group as a whole. CONCLUSION: In patients with angina, AO and CA Dist are related to the severity of coronary atherosclerosis, with the relationship being better for alterations in aortic than in carotid mechanical properties. Large elastic artery (and in particular aortic) stiffening can thus be considered as a marker of the severity of coronary atherosclerosis, providing non-invasive obtainable information on the need to proceed with further clinical examinations. PMID- 17278977 TI - Pharmacological and physicochemical factors in the pressor effects of conjugated haemoglobin-based oxygen carriers in vivo. AB - BACKGROUND: The hypertension induced by haemoglobin-based oxygen carriers could be a result of different pharmacological and physicochemical factors. OBJECTIVE: To investigate whether production of superoxide anion (O2*-) and release of endothelin could be the factors responsible. METHODS: We studied the variation in mean arterial pressure (MAP) in guinea pigs by carrying out a 50% isovolaemic exchange transfusion with conjugated oxyhaemoglobin (non-oxidized form) or conjugated methaemoglobin (fully oxidized form) in the presence or absence of BQ 788 (5 nmol/l), an endothelin receptor type B (ETR-B) antagonist. At key timepoints of variation in MAP, the plasma concentrations of O2*- were measured. The presence of conjugated oxyhaemoglobin and increases in ETR-B concentrations inside the vascular wall were investigated in different vessels, using western blotting. RESULTS: We found that the administration of conjugated oxyhaemoglobin induced a significant increase in MAP, whereas conjugated methaemoglobin had no significant haemodynamic effect. Pretreatment with BQ-788 attenuated the increase in MAP induced by conjugated oxyhaemoglobin. This haemoglobin induced the production of high concentrations of O2*- that declined towards control values after 120 min and decreased in the presence of BQ-788. Western blot analysis showed that the presence of conjugated oxyhaemoglobin inside the vascular wall was time-dependent and correlated with increased ETR-B. CONCLUSION: These results show that the release of O2*- during auto-oxidation of conjugated oxyhaemoglobin is associated with the observed increase in MAP, which may be a result of the vasoconstriction caused by an increase in activation of ETR-B. This activation may be caused by the massive release of endothelin induced by the production of O2*-. PMID- 17278978 TI - Xanthine oxidase-derived extracellular superoxide anions stimulate activator protein 1 activity and hypertrophy in human vascular smooth muscle via c-Jun N terminal kinase and p38 mitogen-activated protein kinases. AB - OBJECTIVE: Vascular xanthine oxidase (XO) activity has been found to be elevated in chronic vascular disease. Although a role for XO in endothelial dysfunction has been proposed, little is known about its influence on vascular smooth muscle maladaptive growth. METHODS: The proliferative and hypertrophic response of human aortic smooth muscle cells (HASMC) stimulated with xanthine/xanthine oxidase (X/XO) was quantified by determining cell number, cell size and protein synthesis. The levels and activity of the growth-related transcription factor activator protein 1 (AP-1) and the activation of mitogen-activated protein kinase (MAPK) by X/XO were determined by either Western blot or transient transfection experiments. RESULTS: X/XO did not affect HASMC proliferation, but led to enhanced planar cell surface area and protein synthesis. In addition, X/XO enhanced c-jun levels and AP-1 transcriptional activity. Although X/XO did not modify extracellular signal-regulated protein kinases 1/2 MAPK or Akt/PKB activity, it promoted the activation of c-Jun N-terminal kinase and p38 MAPK, which were both necessary for X/XO to increase AP-1 activity and cell size in HASMC cultures. Finally, the effects of X/XO on MAPK activation, AP-1 activity and cell size were dependent on the extracellular release of superoxide anions through the enzymatic activity of XO, as they were prevented by both superoxide dismutase and allopurinol. CONCLUSION: X/XO exhibits hypertrophic properties for human vascular smooth muscle, which are mediated by redox-sensitive pathways involving MAPK activation. XO can therefore participate in the maladaptive vascular remodeling observed in chronic cardiovascular diseases exhibiting elevated vascular XO activity. PMID- 17278979 TI - Moderate salt restriction effectively lowers blood pressure and degree of salt sensitivity is related to baseline concentration of renin and N-terminal atrial natriuretic peptide in plasma. AB - OBJECTIVE: The effect of salt restriction on blood pressure is under intense debate. We tested the effect of 100 mmol salt reduction on ambulatory blood pressure (ABP) in 46 Swedish individuals, 39 of whom completed the study, using a double-blind, placebo-controlled, cross-over design. Furthermore, we tested whether the basal plasma concentration of renin or N-terminal atrial natriuretic peptide (Nt-proANP) predict the degree of salt sensitivity. METHODS: Participants received all meals and drinks with a total daily NaCl content of 50 mmol during 8 weeks. In addition, NaCl capsules (100 mmol/day) and corresponding placebo capsules were administered for 4 weeks each in random order. ABP after high-salt intake (150 mmol/day) was compared with ABP after low-salt intake (50 mmol/day). Salt sensitivity was defined as the difference between 24-h systolic ABP at the high-salt versus the low-salt periods. Baseline renin and Nt-proANP were related to salt sensitivity. RESULTS: Lowering of salt intake from 150 to 50 mmol/day induced significant blood pressure reductions (mean reduction, 95% confidence interval) in systolic and diastolic 24-h ABP (5.8, 3.4-8.2 and 2.6, 0.91-4.4 mmHg), daytime ABP (5.5, 2.9-8.1 and 2.3, 0.42-4.1 mmHg) and night-time ABP (6.4, 3.5-9.3 and 3.4, 1.4-5.5 mmHg). Baseline ln(renin) correlated inversely with salt sensitivity (r = -0.50, P = 0.001) whereas baseline ln(Nt-proANP) correlated directly (r = 0.33, P = 0.04). CONCLUSION: Lowering of salt intake with 100 mmol/day induces clinically relevant ABP reductions. Renin and Nt-proANP, measured with individuals on their habitual diet, could be useful biomarkers to identify individuals with the greatest blood pressure-lowering benefit from reduced salt intake. PMID- 17278980 TI - Interactions between aldosterone and connective tissue growth factor in vascular and renal damage in spontaneously hypertensive rats. AB - OBJECTIVE: The aim of the present study was to investigate possible inter relationships between connective tissue growth factor (CTGF) and aldosterone in vascular and renal damage associated with hypertension. METHOD: Spontaneously hypertensive rats (SHR) were treated with two doses (100 and 30 mg/kg per day) of the mineralocorticoid receptor antagonist eplerenone, or with antihypertensive therapy (HHR) (20 mg/kg per day hydralazine + 7 mg/kg per day hydrochlorothiazide + 0.15 mg/kg per day reserpine). RESULTS: CTGF mRNA expression and protein levels in the aorta of SHR were upregulated (P < 0.05) compared with Wistar-Kyoto rats. Both doses of eplerenone similarly and significantly diminished CTGF upregulation, correlated with amelioration of aortic remodelling and endothelium dependent relaxations. Only high-dose eplerenone and HHR significantly reduced arterial blood pressure. HHR treatment also diminished CTGF overexpression, suggesting a blood-pressure-mediated effect in CTGF regulation. This reduction, however, was lower (P < 0.05) than that produced by eplerenone (100 mg/kg per day). The direct effect of aldosterone on vascular smooth muscle cells was also studied. Incubation of cultured vascular smooth muscle cells with aldosterone increased CTGF production in a dose-related manner, but was reduced (P < 0.05) by the mineralocorticoid receptor antagonist spironolactone. Renal CTGF mRNA and protein levels were higher in SHR than in Wistar-Kyoto rats (P < 0.05), and were similarly diminished by all treatments (P < 0.05). CONCLUSIONS: These data show that aldosterone and haemodynamic stress from elevated blood pressure levels regulate vascular and renal CTGF in SHR. The results suggest that aldosterone, through CTGF stimulation, could participate in vascular and renal structural alterations associated with hypertension, describing a novel mechanism of aldosterone in hypertensive target organ damage. PMID- 17278981 TI - Dose-dependent endothelial cell growth and stiffening by aldosterone: endothelial protection by eplerenone. AB - BACKGROUND: Aldosterone at high concentrations causes an expansion of apical surface area and volume of cultured endothelial cells. These morphological changes are associated with endothelial cell stiffening. Here, we tested the hypothesis that the aforementioned aldosterone actions are confined to aldosterone concentrations within the pathophysiological range. Moreover, we investigated whether endothelial cells of venous and arterial origin respond similarly to aldosterone and whether the new aldosterone antagonist eplerenone effectively prevents endothelial cell growth and stiffening. METHODS: We used an endothelial cell line of venous origin (EAHy 926) and primary cultures of human coronary artery endothelial cells (HCAEC). Cells were incubated for 72 h with aldosterone at concentrations of 0.1, 1, 10 and 100 nmol/l. Eplerenone was added at a concentration of 2 micromol/l. Applying atomic force microscopy, we scanned cell layers under fixed and living conditions, allowing measurement of endothelial cell apical surface, volume and cellular stiffness. RESULTS: Aldosterone had comparable effects on EAHy 926 and HCAEC. In EAHy 926, the apical surface increased dose dependently by up to 72 +/- 5% and cell volume by up to 36 +/- 5%. In HCAEC, the maximum increase of apical surface was 78 +/- 6% and maximum cell volume expansion was 58 +/- 6%. Furthermore, aldosterone increased endothelial cell stiffness from 1.47 +/- 0.08 kPa up to 3.95 +/- 0.15 kPa in EAHy 926, and from 1.64 +/- 0.13 kPa up to 4.31 +/- 0.13 kPa in HCAEC. Physiological aldosterone concentrations had no effect, but starting at 1 nmol/l, corresponding to the low pathophysiological range, substantial cell alterations emerged. Eplerenone, at a therapeutic concentration, prevented the observed actions of aldosterone. CONCLUSIONS: Aldosterone-induced endothelial cell growth and stiffening in vitro begins with concentrations in the low pathophysiological range. The preventive action of eplerenone indicates that the endothelium could be a major target of this drug in vivo. PMID- 17278982 TI - Total peripheral resistance responsiveness during the development of secondary renal hypertension in dogs. AB - OBJECTIVE: To determine whether the responses of total peripheral resistance and arterial pressure to vasoconstrictor agents are amplified as renovascular hypertension develops in dogs. METHODS: After baseline measurements, the effects of renal artery stenosis (1K, 1C hypertension) were studied in groups of untreated and enalapril-treated dogs early (1-3 weeks) and later (4-6 weeks) as the hypertension developed. Both resting and open-loop haemodynamic measurements were made and the effects of acute intravenous infusions of vasopressin (0.25, 0.5 and 1.25 ng/kg per min) and phenylephrine (0.125, 0.25 and 0.50 microg/kg per min on arterial pressure, cardiac output and calculated total peripheral resistance responses were measured. RESULTS: Renal artery stenosis induced an increase in arterial blood pressure in both groups of dogs, with similar changes in haemodynamics also observed in open-loop conditions. The slopes of arterial pressure and peripheral resistance responses to vasopressin and phenylephrine were not significantly changed in early or late hypertension, in either the untreated or enalapril-treated groups. CONCLUSIONS: Hypertension from renal artery stenosis in dogs was due to nonautonomic, nonangiotensin II mechanisms. There was no evidence of vascular amplification of the effects of vasoconstrictor agents, indicating that this did not play a role in the development of hypertension. PMID- 17278983 TI - Cardiovascular risk factors in hypertensive patients with coronary artery disease and coexisting renal artery stenosis. AB - OBJECTIVE: The aim of our study was to examine the association between the presence of atherosclerotic renal artery stenosis (RAS) and coexisting cardiovascular risk factors in hypertensive patients with coronary artery disease (CAD). METHODS: A total of 333 consecutive hypertensive patients (239 men, 94 women) with CAD underwent clinically indicated non-emergency coronary angiography, followed by renal angiography. Before catheterization clinical examination was performed to determine demographics, cardiac history, known duration of hypertension, cardiovascular risk factors, features of extracoronary vascular disease and related comorbidities. Blood samples for all biochemical evaluations--including highly sensitive C-reactive protein (hsCRP), fibrinogen and homocysteine--were taken. Ambulatory blood pressure monitoring (ABPM), echocardiography and carotid and femoral ultrasound followed by a duplex colour Doppler examination were performed. RESULTS: Significant RAS (> 50% lumen narrowing) was identified in 40 patients (12%) and non-significant RAS (< 50%) was found in 45 (13.5%) subjects. Patients with significant RAS were older (59.8 versus 56.6 years, P < 0.05) and were characterized by higher systolic ambulatory blood pressure level. Patients with RAS had significantly higher levels of creatinine, hsCRP, fibrinogen and homocysteine and lower creatinine clearance than patients without RAS. Multivessel coronary artery disease (MVD) was more frequent in patients with significant RAS. Patients with significant RAS had significantly higher left ventricular mass index (LVMI) and lower ejection fraction (EF) as compared with those without RAS. Patients with RAS were more often characterized by the presence of carotid and femoral artery atherosclerosis and significantly more pronounced increase in carotid intima-media thickness (IMT) as compared with non-RAS subjects. In a multivariate stepwise logistic regression model carotid IMT [odds ratio (OR) 1.15; 95% confidence interval (CI) 1.03-1.29, P < 0.05], number of coronary arteries stenosed (OR 1.61; 95% CI 1.01 2.56, P < 0.05), creatinine concentration (for 10 micromol/l increase, OR 1.15; 95% CI 1.04-1.28, P < 0.01), body mass index (BMI) (OR 0.86; 95% CI 0.75-0.97, P < 0.05) and number of antihypertensive drugs (OR 1.76; 95% CI 1.18-2.62, P < 0.05) were independently associated with RAS. The areas under receiver operating characteristic curves for carotid IMT, number of coronary arteries stenosed, creatinine concentration, BMI and number of antihypertensive drugs were 0.749, 0.633, 0.703, 0.350 and 0.677, respectively (P < 0.01 for all values). CONCLUSIONS: In conclusion, renal artery stenosis is prevalent in a significant proportion of patients undergoing cardiac catheterization. Renal angiography should be considered particularly in hypertensive patients with multivessel coronary disease coexisting with cardiovascular risk factors, even moderately impaired renal function and increased carotid IMT or vascular disease elsewhere. PMID- 17278985 TI - Impaired renal haemodynamic response to L-arginine in essential hypertension: role of buffering anion and tubuloglomerular feedback. AB - OBJECTIVE: To investigate whether changes in tubuloglomerular feedback (TGF) dependent upon the tubular effects of buffering anions affect the renal haemodynamic response to L-arginine in healthy (control) individuals and patients with essential hypertension. METHODS: Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF) and fractional excretion of sodium (FENa), chloride (FECl) and lithium (FELi) were measured in 10 control individuals and 10 hypertensive patients during two 3-h infusions of 0.012 mmol/kg per min L-arginine buffered with either HCl or citric acid. RESULTS: FELi, FECl and FENa increased (P < 0.001) comparably in controls and hypertensive individuals with arginine-HCl and decreased with arginine-citrate (P < 0.001). MAP was unchanged in controls with arginine-HCl and decreased by 3% with arginine citrate (P < 0.001), and decreased in hypertensive individuals with both arginine HCl and arginine-citrate (by 3 and 7%, respectively; P < 0.001). GFR increased with arginine-citrate in controls and hypertensive individuals (by 6.1 and 5.4%, respectively; P < 0.001), but did not change with arginine-HCl in controls and declined by 4.6% in hypertensive individuals (P < 0.05). RBF increased equally after arginine-citrate in controls and hypertensive individuals (by 34 and 33%, respectively; P < 0.001); it also increased after arginine-HCl (22 and 13%, respectively; P < 0.001), but less than after arginine-citrate (P < 0.001), and 41% less in hypertensive individuals than in controls (P < 0.001). DISCUSSION: Because arginine-HCl, unlike arginine-citrate, inhibits tubular reabsorption and elicits much less renal vasodilatation than does arginine-citrate, renal haemodynamics in response to L-arginine are modulated by changes in reabsorption and TGF according to the tubular effects of the attendant anion. As renal vasodilatation in hypertensive individuals was reduced only with arginine-HCl, which activates TGF, the blunted vasodilatation of the hypertensive kidney in response to arginine-HCl reflects an exaggerated response to an activated TGF. PMID- 17278984 TI - Chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor-beta1 mRNA ameliorates renal injury in hypertensive rats. AB - OBJECTIVE: Transforming growth factor (TGF)-beta is a critical factor in the progression of renal injury, regardless of the primary etiology. Such injury is characterized by glomerular sclerosis and tubulointerstitial fibrosis. To develop a ribozyme-based therapy for progressive renal diseases, we examined the effects of chimeric DNA-RNA hammerhead ribozyme targeting TGF-beta1 mRNA on glomerulosclerosis in salt-loaded, stroke-prone spontaneously hypertensive rats (SHR-SP) and salt-sensitive Dahl (Dahl-S) rats. METHODS: The chimeric DNA-RNA ribozyme to TGF-beta1 was delivered by polyethylenimine to cultured mesangial cells from SHR-SP in vitro and to glomeruli in SHR-SP in vivo. The chimeric ribozyme reduced expression of TGF-beta1 mRNA and protein, which was accompanied by inhibition of expression of extracellular matrix molecules such as fibronectin and collagen type I in mesangial cells from SHR-SP in vitro. RESULTS: One intraperitoneal injection of 200 microg of chimeric DNA-RNA ribozyme to TGF-beta1 in vivo markedly ameliorated thickening of capillary artery walls and glomerulosclerosis in salt-loaded SHR-SP and Dahl-S rats without a reduction in blood pressure. The chimeric ribozyme reduced expression of TGF-beta1 and connective tissue growth factor (CTGF) mRNAs in renal cortex in salt-loaded Dahl S rats. Chimeric ribozyme to TGF-beta1 significantly reduced levels of protein in urine in the Dahl-S rats. CONCLUSION: These results suggest that chimeric DNA-RNA ribozyme to TGF-beta1 may be useful as a gene therapy for progressive tissue injury in a wide variety of renal diseases, including hypertensive nephrosclerosis. PMID- 17278986 TI - Rates and determinants of reinitiating antihypertensive therapy after prolonged stoppage: a population-based study. AB - OBJECTIVE: To assess patterns of restarting antihypertensive drugs after a prolonged period of discontinuation. METHODS: We conducted a retrospective cohort study among new users of blood pressure-lowering medication in the PHARMO database in The Netherlands, who had a period of at least 180 days without such medication. A multivariable Cox proportional hazard analysis was used to explore the baseline variables associated with reinitiating treatment. Case-crossover analysis was used to evaluate determinants of reinitiating treatment. RESULTS: We identified 35,714 patients as initiating blood pressure-lowering treatment during the period 1 January 1999 to 30 June 2004. Of the 18,357 (51.4%) patients who discontinued blood pressure-lowering treatment, 19.3% restarted treatment within 1 year and 60.7% restarted within 6 years. With every additional year they had been on therapy, patients were more likely to restart [odds ratio (OR) = 1.38; 95% confidence interval (CI) = 1.34-1.42]. The case-crossover analysis revealed that hospitalization for cardiovascular disease (OR = 2.20; 95% CI = 1.84-2.63), as well as refilling of another cardiovascular medication (OR = 1.25; 95% CI = 1.11-1.40), were each independently associated with reinitiating treatment. Refilling non-cardiovascular medications was not associated with reinitiating treatment (OR = 1.03; 95% CI = 0.97-1.10). CONCLUSION: Physicians should be aware that many patients have prolonged periods of discontinuation during the use of blood pressure-lowering medication, and that most of these patients will eventually resume therapy. Ongoing refilling other medications is not associated with reinitiating treatment. This suggests that, for some patients, the decision to discontinue may be drug specific rather than a behavioural characteristic applicable to all chronic treatments. PMID- 17278987 TI - Perindopril-based blood pressure-lowering therapy reduces amino-terminal-pro-B type natriuretic peptide in individuals with cerebrovascular disease. AB - OBJECTIVE: The plasma amino-terminal-pro-B-type natriuretic peptide (NT-proBNP) level predicted congestive heart failure, myocardial infarction, and ischaemic stroke in participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of the effects of blood pressure lowering on cardiovascular events among individuals with cerebrovascular disease. Active treatment comprised a flexible regimen based on perindopril, with the addition of indapamide at the discretion of treating physicians. Active treatment reduced cardiovascular events, and we therefore investigated whether active treatment modified NT-proBNP and other cardiovascular risk factors. METHODS: We measured NT-proBNP and other cardiovascular risk factors at randomization and after 13 months of therapy in a subset of 357 PROGRESS participants. RESULTS: Baseline systolic and pulse pressures were higher in individuals with elevated baseline NT-proBNP levels. In comparison with placebo, active treatment reduced the blood pressure and NT-proBNP levels, and increased renin levels. Reduction of NT-proBNP levels by active treatment was most evident in individuals with baseline NT-proBNP levels in the highest quarter (> 26 pmol/l), with a median reduction of 16 pmol/l (interquartile range 0-51 pmol/l, P = 0.004), corresponding to a median decrease of 39% (interquartile range 0-69%). Active treatment reduced blood pressure similarly for individuals in each of the four quarters of baseline NT-proBNP. Active therapy had no effect on plasma lipid, C reactive protein, homocysteine, or soluble vascular cell adhesion molecule 1 levels. CONCLUSION: We conclude that plasma NT-proBNP level, in addition to predicting cardiovascular risk, may provide a measure of risk reduction by blood pressure-lowering therapy. PMID- 17278988 TI - Ambulatory blood pressure monitoring after 1 year on valsartan or amlodipine based treatment: a VALUE substudy. AB - OBJECTIVE: The ambulatory blood pressure (ABP) monitoring substudy of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was carried out in a subset of patients from USA, Italy and Denmark. ABP was measured after 1 year in the trial, with the aim of evaluating comparability of ABP levels on valsartan (VAL) and amlodipine (AML)-based regimens. METHODS: ABP was measured every 20 min during a 25-h period after morning administration of medicine; 659 patients were available for intention-to-treat analysis. RESULTS: Office blood pressure (BP) differences were smaller than in the main study and mean ABP levels also showed only minor differences between the two regimens (VAL, 132.5/74.8 mmHg; AML, 131.5/75.2 mmHg). However, during the first 7 h after dosing, ABP was lower on VAL, whereas AML exerted a significantly stronger effect during the last 4 h of the dosing interval--possibly influencing the differences in office BP found in the main study. Mean heart rate (HR) was higher on AML (72.3 bpm) than on VAL (70.5 bpm) (P = 0.013), suggesting a sustained difference in sympathetic activation. Correlation analysis showed a close relationship between treated ABP levels and the occurrence of combined cardiovascular endpoints--superior to the relationship to office BP. CONCLUSIONS: In these elderly high-risk patients, diastolic ABP levels tended to be less predictive than systolic, and daytime less predictive than night-time for all cardiovascular endpoints. The findings underline the importance of ABP substudies in comparative trials for elucidating significant differences in pharmacodynamics, and stresses the superior predictive power of ABP. PMID- 17278989 TI - Claims in advertisements for antihypertensive drugs in a Dutch medical journal. AB - BACKGROUND: Advertising claims must not conflict with the official summary of product characteristics. After a drug has been approved, new clinical evidence may become available. AIMS: To determine how the pharmaceutical industry deals with evolving clinical evidence in advertising claims for antihypertensive drugs, and whether such pharmaceutical promotion is up to standard. METHODS: We examined all advertisements from the Dutch Journal of Medicine published between 1996 and 2004. We judged whether claims were in agreement with the information available from the summary of product characteristics or evidence from cited clinical trials. Subsequently, we reviewed whether these claims had been assessed by the Code of Practice authority. RESULTS: We identified 50 unique advertisements with, in total, 492 appearances for 16 antihypertensive drugs. Claims of blood pressure lowering and convenient use were all judged to be sufficiently substantiated. For calcium-channel blockers, insufficiently supported safety claims had been made in three cases (41 appearances). Claims suggesting effects on long-term outcomes started in 1999 for angiotensin II receptor blockers, and were made during the whole period for several other antihypertensive drugs. In 16 cases (135 appearances), such claims were not supported by the available information. Some claims were premature, others transferred results from a specific patient group to the general population of hypertensive patients. Only two cases were reviewed by the Code of Practice authority. CONCLUSIONS: Overall, 35% of the advertisements for antihypertensive drugs contained suggestive claims not supported by the offered evidence. The current system of self-regulation cannot ensure that pharmaceutical promotion is always accurate, balanced and evidence based. PMID- 17278991 TI - Dysfunction of the autonomic nervous system as a possible explanation of non dipping phenomenon in insulin-resistant obese subjects. PMID- 17278992 TI - Time to end a doubt: is pulse wave analysis a valid measure for central arterial blood pressure and arterial stiffness? PMID- 17278993 TI - Global challenge for overcoming high blood pressure: Fukuoka Statement, 19 October 2006. PMID- 17278994 TI - Layer-specific markers as probes for neuron type identity in human neocortex and malformations of cortical development. AB - Malformations of cortical development (MCDs) are heterogeneous disorders caused by abnormalities of cell proliferation, apoptosis, cell migration, cortical organization, and axon pathfinding. In severe MCDs, the cerebral cortex can appear completely disorganized, or may be replaced by aberrant laminar patterns, as in "4-layered" types of lissencephaly and polymicrogyria. Little is known about the abnormal layers in MCDs and whether they bear any relation to normal cortical layers or how MCDs affect specific neuron types. Normally, each layer contains a defined mixture of different types of pyramidal and nonpyramidal neurons. The neuron types are distinguished by molecular expression as well as morphologic, neurochemical, and electrophysiologic criteria. Patterns of layer specific mRNA and protein expression reflect the segregation of different neuron types into different layers (e.g. corticospinal projection neurons in layer V). Numerous layer-specific markers have been described in rodent cortex, and increasing numbers are being documented in human and monkey cortex. Applied to MCDs, layer-specific markers have the potential to reveal new insights on pathogenesis, treatment possibilities, and genotype-phenotype correlations. However, much work remains before layer-specific markers become practical tools in diagnostic neuropathology. Additional markers, more extensive documentation of normal expression, and better antibodies compatible with paraffin-embedded tissues will be necessary. PMID- 17278995 TI - Detection of bone marrow-derived cells expressing a neural phenotype in the human brain. AB - Animal studies suggest that adult bone marrow cells have the potential to migrate into the brain and generate new neural cells. Because data on this physiologic repair mechanism in humans are lacking, we investigated bone marrow engraftment into the brain of bone marrow recipients after sex-mismatched transplantation. Brain sections of seven allogeneic female bone marrow recipients were examined. The Y-chromosome, which served as a natural marker of donor bone marrow-derived cells after male-to-female transplantation, was identified by in situ hybridization. The neural phenotype of Y-chromosome-positive cells was determined using neural nuclear protein (NeuN) immunohistochemistry. Y-chromosome-positive cells expressing NeuN were found within the first 3 months after transplantation in both the cerebrum and the cerebellum at a frequency of 0.003% to 0.013% of all neurons. These cells were observed only in patients with cerebral lymphocytic infiltration and graft-versus-host disease. Our data suggest that adult bone marrow cells are capable of generating cells that express the neural marker NeuN early after transplantation. Cells with this specific phenotype may contribute to tissue repair in brain regions remote from neurogenic zones. PMID- 17278996 TI - Methyl CpG-binding protein 2 (a mutation of which causes Rett syndrome) directly regulates insulin-like growth factor binding protein 3 in mouse and human brains. AB - Rett syndrome (RTT) is a major neurodevelopmental disorder, characterized by mental retardation and autistic behavior. Mutation of the MeCP2 gene, encoding methyl CpG-binding protein 2, causes the disease. The pathomechanism by which MeCP2 dysfunction leads to the RTT phenotype has not been elucidated. We found that MeCP2 directly regulates expression of insulin-like growth factor binding protein 3 (IGFBP3) gene in human and mouse brains. A chromatin immunoprecipitation assay showed that the IGFBP3 promoter contained an MeCP2 binding site. IGFBP3 overexpression was observed in the brains of mecp2-null mice and human RTT patients using real-time quantitative polymerase chain reaction and Western blot analyses. Moreover, mecp2-null mice showed a widely distributed and increased number of IGFBP3-positive cells in the cerebral cortex, whereas wild type mice at the same age showed fewer IGFBP3-positive cells. These results suggest that IGFBP3 is a downstream gene regulated by MeCP2 and that the previously reported BDNF and DLX5 genes and MeCP2 may contribute directly to the transcriptional expression of IGFBP3 in the brain. Interestingly, the pathologic features of mecp2-null mice have some similarities to those of IGFBP3-transgenic mice, which show a reduction of early postnatal growth. IGFBP3 overexpression due to lack of MeCP2 may lead to delayed brain maturation. PMID- 17278997 TI - The epsilon isoform of 14-3-3 protein is a component of the prion protein amyloid deposits of Gerstmann-Straussler-Scheinker disease. AB - The 14-3-3 proteins are highly conserved, ubiquitous molecules involved in a variety of biologic events, such as transduction pathway modulation, cell cycle control, and apoptosis. Seven isoforms have been identified that are abundant in the brain, preferentially localized in neurons. Remarkable increases in 14-3-3 are seen in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease (CJD), and it has been found in pathologic inclusions of several neurodegenerative diseases. Moreover, the zeta isoform has been detected in prion protein (PrP) amyloid deposits of CJD patients. To further investigate the cerebral distribution of 14-3-3 in prion-related encephalopathies, we carried out an immunohistochemical and biochemical analysis of brain tissue from patients with Gerstmann-Straussler-Scheinker disease (GSS) and sporadic, familial and acquired forms of CJD, using specific antibodies against the seven 14-3-3 isoforms. The study showed a strong immunoreactivity of PrP amyloid plaques of GSS patients for the 14-3-3 epsilon isoform, but not for the other isoforms. The epsilon isoform of 14-3-3 was not found in PrP deposits of CJD. These results indicate that the epsilon isoform of 14-3-3 is a component of PrP amyloid deposits of GSS and suggest that this is the sole 14-3-3 isoform specifically involved in the neuropathologic changes associated with this disorder. PMID- 17278998 TI - The histopathology of hypothalamic hamartomas: study of 57 cases. AB - Hypothalamic hamartomas (HHs) are rare developmental tumors that cause seizures or pituitary axis dysfunction, usually beginning in childhood. We analyzed HH tissue from 57 patients whose tumors were resected through recently developed transcallosal interforniceal and transventricular endoscopic surgical approaches. All cases were composed of abnormally distributed but cytologically normal neurons and glia, including fibrillary astrocytes and oligodendrocytes. Neuronal elements predominated in most cases, but a relative increase in astrocytic elements was seen with increasing age. All had various sized nodular foci of neurons as well as areas of diffusely distributed neurons with interspersed glial cells. Smaller neurons predominated, and most cases had only a few interspersed large ganglion cells. Immunohistochemistry demonstrated extensive production of synapse-associated proteins. Immunohistochemistry for phosphorylated and nonphosphorylated neurofilament and alpha-internexin demonstrated staining patterns consistent with mature neurons. In contrast to cortical dysplasia, atypical large ganglion-like balloon cells were almost never seen. In summary, although their number and distribution vary, mature smaller neurons were the most prominent and most consistent histologic feature of HH. Nodules of these small neurons were a universal feature of the microarchitecture of HH lesions associated with epilepsy. Characterization of these neurons may aid in understanding the mechanism of seizure development in HH. PMID- 17278999 TI - Neuropathologic features of frontotemporal lobar degeneration with ubiquitin positive inclusions with progranulin gene (PGRN) mutations. AB - Frontotemporal lobar degeneration is heterogeneous; cases with tau- and synuclein negative, ubiquitin-positive neuronal inclusions are the most common, and some have mutations in the gene for progranulin (PGRN). The purpose of this study was to determine whether there were distinctive clinical and neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions with PGRN mutations. A retrospective review of medical records and semiquantitative neuropathologic analysis was performed on 18 PGRN(+) and 24 PGRN(-) cases. Clinically, PGRN(+) cases had more frequent language impairment and parkinsonism. Pathologically, PGRN(+) cases had smaller brains, more marked global atrophy, and more frontal atrophy. There was no difference in the frequency of hippocampal sclerosis. The pathology of PGRN(+) cases was relatively homogeneous, whereas PGRN(-) cases were more heterogenous. PGRN(+) cases had greater density of cortical ubiquitin-immunoreactive lesions, especially dystrophic neurites in layer II. Intranuclear inclusions were present in all PGRN(+) and 42% of PGRN(-) cases. The results suggest that frontotemporal lobar degeneration with ubiquitin positive inclusions due to PGRN mutations has several characteristic features, including ubiquitin-immunoreactive neuritic pathology in superficial cortical layers and neuronal intranuclear inclusions. On the other hand, there is no histopathologic feature or combination of features that is pathognomonic. Neuronal intranuclear inclusions are virtually always present, but they can be detected in PGRN(-) cases. PMID- 17279000 TI - TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. AB - Frontotemporal dementia with inclusion body myopathy and Paget disease of bone is a rare, autosomal-dominant disorder caused by mutations in the gene valosin containing protein (VCP). The CNS pathology is characterized by a novel pattern of ubiquitin pathology distinct from sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) without VCP mutations. TAR DNA binding protein 43 (TDP-43) was recently identified as a major disease protein in the ubiquitin-positive inclusions of sporadic and familial FTLD-U. To determine whether the ubiquitin pathology associated with mutations in VCP is characterized by the accumulation of TDP-43, we analyzed TDP-43 in the CNS pathology of five patients with VCP gene mutations. Accumulations of TDP-43 colocalized with ubiquitin pathology in inclusion body myopathy and Paget disease of bone, including both intranuclear inclusions and dystrophic neurites. Similar to FTLD-U, phosphorylated TDP-43 was detected only in insoluble brain extracts from affected brain regions. Identification of TDP-43, but not VCP, within ubiquitin-positive inclusions supports the hypothesis that VCP gene mutations lead to a dominant negative loss or alteration of VCP function culminating in impaired degradation of TDP-43. TDP-43 is a common pathologic substrate linking a variety of distinct patterns of FTLD-U pathology caused by different genetic alterations. PMID- 17279001 TI - Neurofibrillary tangles may interfere with Smad 2/3 signaling in neurons. AB - Transforming growth factor (TGF)-beta is a multifunctional cytokine with anti inflammatory, reparative and neuroprotective functions. Increased levels of TGFbeta in Alzheimer disease (AD) are associated with perivascular deposition of extracellular matrix, which may impair clearance of beta-amyloid and contribute to the development of cerebral amyloid angiopathy. TGFbeta signaling is transduced by Smad proteins: on TGFbeta receptor activation, Smads 2 and 3 are released from sequestration by microtubules, phosphorylated (forming pSmad2/3), and, together with Smad 4, translocated to the nucleus, where they initiate the transcription of multiple genes. Neuronal microtubule assembly is disturbed in AD when tau, a microtubule-stabilizing protein, is hyperphosphorylated and forms neurofibrillary tangles. We have investigated the relationship between Ser202 phospho-tau and pSmads 2 and 3 in the temporal lobe in AD. Within neurons in control brains, pSmads 2 and 3 were almost exclusively intranuclear. In AD, pSmad 3 bound to phospho-tau (mostly insoluble tau) and accumulated in the cytoplasm of tangle-bearing neurons; this was accompanied by a marked decrease in nuclear pSmad3. pSmads 2 and 3 were also present in neuronal granulovacuolar inclusions. Our findings suggest that neurofibrillary tangles sequester pSmad3, preventing its translocation into the nucleus and the induction of gene transcription. Interference with the Smad signaling may adversely affect survival of tangle bearing neurons in AD. PMID- 17279002 TI - Visceral leishmaniasis: bone marrow biopsy findings. AB - Visceral leishmaniasis (VL) or Kala-azar is a common parasitic infection among children in Iran. The records of 249 children with VL were evaluated retrospectively. The clinical, hematologic, and bone marrow biopsy findings were studied. In particular, we assessed whether there was an association between bone marrow biopsy findings and prognosis. Five major groups were identified: (1) hypercellular marrow with many Leishman Donovan (LD) bodies, (2) multiple noncaseating granulomas with a few LD bodies, (3) diffuse fibrosis with rare LD bodies, (4) benign lymphoid nodules with many LD bodies, and (5) marrow necrosis with many LD bodies. The patients with hypercellular marrow and benign lymphoid nodules were alive and responded well to glucantime therapy. The patients with marrow fibrosis and marrow necrosis died and were resistant to any type of therapy. Patients with granulomas did not respond to glucantime therapy but responded to amphotericin B. However, less than half of the patients died owing to malnutrition and misdiagnosis. We correlated the bone marrow biopsy findings with the treatment outcomes and prognosis. The outcome was excellent in cases of hypercellular marrow, very poor in cases of fibrosis and necrosis, and intermediate in cases of granulomas. As a result, we believe that bone marrow biopsy findings can be helpful for assessing the prognosis of VL patients. PMID- 17279003 TI - Improved outcome from invasive adenovirus infection in pediatric patients after hemopoietic stem cell transplantation using intensive clinical surveillance and early intervention. AB - Adenovirus is a common cause of morbidity and mortality after hemopoietic stem cell transplantation in children. Recently the incidence, risk factors, and outcome of such infections have been better defined using improved virologic detection methods, in particular polymerase chain reaction. We have introduced intensive virologic surveillance for adenovirus in our institution including at least weekly polymerase chain reaction testing of blood and stool samples. We report on 71 prospectively monitored transplants, including 40 from unrelated donors. In total, there were 8 cases of invasive adenovirus infection, 3 of whom died. Mortality was less than in previous studies as cases were managed with antiviral chemotherapy and reduction of immune suppression. In fatal cases, there was concurrent difficult graft versus host disease making withdrawal of immune suppression therapy impossible. We describe 2 cases of graft failure in association with adenovirus viremia and its treatment that were successfully managed with further donor cell infusion. PMID- 17279005 TI - Chronic immune thrombocytopenic purpura in children: a survey of the canadian experience. AB - BACKGROUND: Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorder with heterogeneous manifestations and a natural history that is not fully understood. To better understand the natural history of chronic ITP and detect response trends and outcomes of therapy, we conducted a 10 year retrospective survey of children from age 1 to 18 years with a diagnosis of chronic ITP. RESULTS: Data on 198 patients from 8 Canadian Pediatric Hematology/Oncology centers were analyzed. The majority of patients were female (58%), and were previously diagnosed with acute (primary) ITP (85%). The age at diagnosis of chronic ITP ranged from 1.1 to 17.2 years with a mean of 8.2+/-4.4 years. Ninety percent of patients received some form of treatment. Untreated patients had a higher mean platelet count at diagnosis of chronic ITP (P=0.009) despite similarities in mean age at first presentation and mean duration of follow-up. Thirty-four (17%) patients underwent splenectomy. Splenectomized patients tended to be significantly older, had a lower mean platelet count at diagnosis of chronic ITP, and had a longer duration of follow-up. CONCLUSIONS: The results from this study are consistent with published reports. PMID- 17279004 TI - Multicenter randomized trial of chewing gum for preventing oral mucositis in children receiving chemotherapy. AB - The properties of saliva led us to hypothesize that the salivary flow increase induced by gum chewing might protect the oral mucosa from lesions due to cancer chemotherapy. We conducted a multicenter randomized trial to evaluate the efficacy of chewing gum in preventing oral mucositis in 145 children receiving chemotherapy regimens expected to induce WHO grade 3-4 oral mucositis in at least 30% of patients. Patients were allocated at random to standard oral care with or without 5 gum pieces per day. No overall reduction in severe oral mucositis occurred in the gum arm (51%) compared with the standard arm (44%). VIDE, COPADM, and multidrug intensive chemotherapy caused severe oral mucositis in 75% of patients in both arms. In patients receiving less toxic regimens, a decrease in WHO grade 1-4 oral mucositis was noted in the gum arm compared with the standard arm (49% vs. 72%, P=0.03). In the multivariate analysis, the risk of oral mucositis was related only to the type of chemotherapy regimen, suggesting that further strategies for preventing oral mucositis could be mainly based on these criteria. PMID- 17279006 TI - Topotecan and etoposide in the treatment of relapsed high-risk neuroblastoma: results of a phase 2 trial. AB - We initiated a phase 2 trial with a combination of topotecan and etoposide (TE) in patients with relapse after intensive first line chemotherapy for neuroblastoma. TE chemotherapy consisted of topotecan (schedule A: 1.0 mg/m2/d 30 minute-infusion days 1 to 5, B: 0.7 mg/m2/d continuous infusion days 1 to 7, and C: 1.0 mg/m2/d continuous infusion days 1 to 7) followed by etoposide (100 mg/m2/d 1-hour-infusion days 8 to 10). TE was repeated every 28 days. The treatment was continued until severe nonhematopoietic toxicity or progression occurred or the treating physician chose alternative consolidation treatment after response to TE. Forty patients received 153 TE cycles. Grades 3 to 4 leukopenia was frequently observed in all schedules (A 51% of cycles, B 48%, and C 74%, P=0.141). Thrombocytopenia (A 69%, B 63%, and C 93%, P=0.004) and neutropenic fever (A 12%, B 29%, and C 37%, P=0.048) occurred more frequently in schedule C. No treatment-related fatal toxicity was observed. Among 36 patients evaluable for response, 4 patients achieved complete and 13 patients achieved partial remission (47%). We conclude that the combination of TE is effective and tolerable in the treatment of relapsed high-risk neuroblastoma. PMID- 17279008 TI - Posttransplant Hodgkin lymphoma preceded by polymorphic posttransplant lymphoproliferative disorder: report of a pediatric case and review of the literature. AB - Epstein-Barr virus-mediated posttransplant lymphoproliferative disorder (PTLD) is a well-recognized complication of immunosuppression in transplant patients and has broad clinical manifestations and pathologic features ranging from reactive lymphoid proliferation to malignant lymphoma. The category of Hodgkin lymphoma and Hodgkin lymphomalike PTLD is an uncommon variant of PTLD. Development of Hodgkin lymphoma subsequent to other subtypes of PTLD in the same patient is even more unusual, especially in pediatric patients. In this report, we describe a pediatric case of Epstein-Barr virus-associated posttransplant Hodgkin lymphoma developing several years after the patient was diagnosed with polymorphic PTLD and review the literature of the previously reported cases in children to further help characterize the clinical features, histopathologic appearances, biology, and treatment strategies of this uncommon entity. PMID- 17279007 TI - Role of procalcitonin and CRP in differentiating a stable from a deteriorating clinical course in pediatric febrile neutropenia. AB - In clinical practice, when neutropenic-fever patients present with no microbiologically and clinically defined infection, the risk of underestimating an occult infection is of major concern, the clinicians have to make a decision on when to modify antibiotic therapy. Hence, a reliable, specific, and sensitive marker, which is regulated independently from the leukocyte count and the underlying disease, is needed for the early diagnosis of infections in cases of neutropenic fever. We have evaluated the diagnostic and follow-up value of procalcitonin (PCT) compared with C-reactive protein (CRP) and erythrocyte sedimentation rate in documenting the infection in neutropenic-fever patients undergoing intensive chemotherapy, as evidenced by the durational change in these parameters in the presence of defined infection. Forty-nine patients, who had 60 febrile episodes, and who were hospitalized in the Hacettepe University Ihsan Dogramaci Children's Hospital between January 1, 2004 and January 1, 2005 were included in this prospective study. All patients had been diagnosed with neutropenic fever after intensive chemotherapy. In our study, PCT and CRP levels were significantly higher in neutropenic-fever patients (group I and group II separately) than in control patients (P<0.001) throughout the study period; but erythrocyte sedimentation rate levels did not show any significant difference (P>0.05). In sequential analyses of patients without documented infections, the median of PCT concentrations shows a tendency to fall after the 8th hour of onset of fever, whereas in patients with documented infections PCT concentrations fell after the 48th hour. In conclusion, our study suggests that PCT, when measured periodically, is a more useful diagnostic inflammation parameter in pediatric neutropenic-fever patients than CRP, both in estimating the severity of the infection and, the duration and origin of the fever. Hence, PCT might be helpful when deciding on initial therapy modification. PMID- 17279009 TI - Peritoneal hemorrhage due to a ruptured ovarian cyst in ITP. AB - Immune thrombocytopenic purpura in children rarely causes severe bleeding. The incidence of intracranial hemorrhage is approximately 0.2% to 1.0%, and severe bleeding (defined as persistent epistaxis, melena, menorrhagia, gastrointestinal bleeding, etc, requiring hospitalization or transfusion) occurs in only 5% of patients. Epstein-Barr virus (EBV) associated idiopathic thrombocytopenic purpura (ITP) tends to behave similarly to non-EBV - associated ITP with no increase in hemorrhagic complications and only a small increase in time to remission. Immune thrombocytopenic purpura diagnosed in adolescence is more likely to be chronic then in childhood ITP, but has a higher rate of spontaneous resolution than in adults. However, females in this age group are in their early childbearing years and present a unique set of possible hemorrhagic complications not seen in younger patients. We present the case of an 18-year-old female with EBV associated ITP, who developed a severe intra-abdominal bleed secondary to a hemorrhagic ovarian cyst. PMID- 17279010 TI - Isolated pulmonary Langerhans cell histiocytosis in a 17-year-old male. AB - We report a case of a previously healthy 17-year-old male with a history of cigarette smoking, who presented with acute development of respiratory distress. Computed tomography demonstrated cystic pulmonary changes. A lung biopsy confirmed Langerhans cell histiocytosis (LCH). The definitive diagnosis was isolated pulmonary LCH, a disorder that is infrequently found in adults, and rarely in children. We know of only one other case of a previously healthy adolescent cigarette smoker who developed isolated pulmonary LCH. The etiology of pulmonary LCH is unknown, but smoking has been considered as a risk factor. PMID- 17279011 TI - Severe autoimmune hemolytic anemia after unrelated umbilical cord blood transplant for familial hemophagocytic lymphohistiocytosis: significant improvement after treatment with rituximab. AB - A 4-month-old girl diagnosed with familial hemophagocytic lymphohistiocytosis underwent a matched unrelated, umbilical cord blood transplant. Six weeks later she developed severe acute autoimmune hemolytic anemia and thrombocytopenia requiring multiple transfusions. This was refractory to high-dose steroid and intravenous immunoglobulin, but did respond to Rituximab (anti-CD20 monoclonal antibody) 375 mg/m2. Hemolysis recurred after steroid tapering but responded to a second course of Rituximab. This case report highlights the difficulty in managing posttransplant autoimmune hemolytic anemia. PMID- 17279012 TI - Hereditary pyropoikilocytosis: a rare but potentially severe form of congenital hemolytic anemia. AB - Hereditary pyropoikilocytosis is an inherited red cell membrane disorder with characteristic morphology: striking anisopoikilocytosis with red cell fragmentation and microspherocytes. Clinical and laboratory physicians must be aware of the potential impact of this disorder on accuracy of complete blood count results reported by automated hematology instruments. Recognition of the morphologic and laboratory findings are important for recognizing this potentially severe anemia. PMID- 17279013 TI - Possible increase of the neurotoxicity of vincristine by the concurrent use of posaconazole in a young adult with leukemia. PMID- 17279015 TI - Intended and unintended consequences: what should we really worry about? PMID- 17279016 TI - Are continuity of care and teamwork incompatible? PMID- 17279018 TI - Multidisciplinary primary care teams: effects on the quality of clinician-patient interactions and organizational features of care. AB - BACKGROUND: Multidisciplinary teams may hold promise for improving primary care quality. This study examined the influence of multidisciplinary teams on patients' assessments of primary care, including access, integration, and clinician-patient interaction quality. METHODS: From January 2004 through March 2005, a large multispecialty practice in Massachusetts obtained data monthly from patients of 145 primary care physicians using a well-validated patient questionnaire. The analytic sample included respondents with at least 2 primary care visits over the study period (n=14,835). For each respondent, administrative data were used to compute visit continuity over the study period and to classify each primary care visit as PCP, on-team, or off-team. Multivariate regression modeled the relationship of visit continuity to each primary care measure. RESULTS: Approximately one-third of patients (35%) saw only their PCP; 15% had only PCP and "on-team" visits; 9% had a mix of PCP, on-, and off-team visits; and 41% had only "off-team" visits when not seeing their PCP. Greater PCP continuity was associated with more favorable scores on nearly all measures (P<0.001). An exception was patients' assessments of teams, which were better when on- versus off-team visits occurred (P<0.01). For other measures, the decrements associated with discontinuity were the same irrespective of whether discontinuities involved on- or off-team visits. CONCLUSIONS: The finding that PCP visit discontinuities are associated with more negative care experiences, irrespective of whether discontinuities involve on- or off-team visits, highlights the challenges of incorporating teams into primary care in ways that patients experience as value added rather than disruptive to primary care relationships. PMID- 17279017 TI - The effect of a quality improvement initiative on the quality of other aspects of health care: the law of unintended consequences? AB - PROBLEM: Policymakers and clinicians are concerned that initiatives to improve the quality of care for some conditions may have unintended negative consequences for quality in other conditions. OBJECTIVE: We sought to determine whether a practice redesign intervention that improved care for falls, incontinence, and cognitive impairment by an absolute 15% change also affected quality of care for masked conditions (conditions not targeted by the intervention). DESIGN, SETTING, AND PARTICIPANTS: Controlled trial in 2 community medical groups, with 357 intervention and 287 control patients age 75 years or older who had difficulty with falls, incontinence, or cognitive impairment. INTERVENTION: Both intervention and control practices implemented case-finding for target conditions, but only intervention practices received a multicomponent practice change intervention. Quality of care in the intervention practices improved for 2 of the target conditions (falls and incontinence). MAIN OUTCOME MEASURES: Percent of quality indicators satisfied for a set of 9 masked conditions measured by abstraction of medical records. RESULTS: Before the intervention, the overall percent of masked indicators satisfied was 69% in the intervention group and 67% in the control group. During the intervention period, these percentages did not change, and there was no difference between intervention and control groups for the change in quality between the 2 periods (P=0.86). The intervention minus control difference-in-change for the percent of masked indicators satisfied was 0.2% (bootstrapped 95% confidence interval, -2.7% to 2.9%). Subgroup analyses by clinical condition and by type of care process performed by the clinician did not show consistent results favoring either the intervention or the control group. CONCLUSION: A practice-based intervention that improved quality of care for targeted conditions by an absolute 15% change did not affect measurable aspects of care on a broad set of masked quality measures encompassing 9 other conditions. PMID- 17279020 TI - The Safety Organizing Scale: development and validation of a behavioral measure of safety culture in hospital nursing units. AB - BACKGROUND: Evidence that medical error is a systemic problem requiring systemic solutions continues to expand. Developing a "safety culture" is one potential strategy toward improving patient safety. A reliable and valid self-report measure of safety culture is needed that is both grounded in concrete behaviors and is positively related to patient safety. OBJECTIVE: We sought to develop and test a self-report measure of safety organizing that captures the behaviors theorized to underlie a safety culture and demonstrates use for potentially improving patient safety as evidenced by fewer reported medication errors and patient falls. SUBJECTS: A total of 1685 registered nurses from 125 nursing units in 13 hospitals in California, Indiana, Iowa, Maryland, Michigan, and Ohio completed questionnaires between December 2003 and June 2004. RESEARCH DESIGN: The authors conducted a cross-sectional assessment of factor structure, dimensionality, and construct validity. RESULTS: The Safety Organizing Scale (SOS), a 9-item unidimensional measure of self-reported behaviors enabling a safety culture, was found to have high internal reliability and reflect theoretically derived and empirically observed content domains. The measure was shown to discriminate between related concepts like organizational commitment and trust, vary significantly within hospitals, and was negatively associated with reported medication errors and patient falls in the subsequent 6-month period. CONCLUSIONS: The SOS not only provides meaningful, behavioral insight into the enactment of a safety culture, but because of the association between SOS scores and reported medication errors and patient falls, it also provides information that may be useful to registered nurses, nurse managers, hospital administrators, and governmental agencies. PMID- 17279019 TI - Facility-level factors influencing chronic heart failure care process performance in a national integrated health delivery system. AB - BACKGROUND: Gaps between evidence and practice in the care of patients with chronic heart failure (CHF) in the United States suggest major opportunities for improvement. However, the organizational factors and implementation approaches that influence adherence to national guidelines are poorly understood. OBJECTIVES: The objectives of this study were to explore the degree to which providers in the Veterans Health Administration system adhere to CHF clinical practice guidelines, and to identify facility-level factors influencing adherence. DESIGN: In a national cross-sectional study, facility quality managers were surveyed regarding quality improvement efforts, guideline implementation, and context. These data were linked to organizational structure data and provider adherence data from chart reviews. The unit of analysis was the facility. The data were adjusted for the average number of comorbidities per CHF patient. Multivariate logistic regression models were constructed to model factors affecting adherence to CHF guidelines. SAMPLE: The sample consisted of 143 Veterans Administration Medical Centers with ambulatory care clinics. RESULTS: The quality manager survey included data from 91% of facilities. Facility-level estimates of provider adherence measures were, on average, 85% or more for most measures. In multivariate analyses, facilities with higher levels of adherence were more likely to have: (1) providers who had been given a brief guideline summary, (2) providers receptive to the guidelines, (3) guideline-specific task forces to support implementation, and 4) a well-planned implementation process. CONCLUSIONS: Healthcare organizations should adapt implementation to meet local conditions, including creating guideline-specific task forces, developing a well planned implementation process, fostering provider buy-in, and providing guideline summaries to providers. PMID- 17279021 TI - The complexity of care for patients with rheumatoid arthritis: metrics for better understanding chronic disease care. AB - BACKGROUND: Patients with rheumatoid arthritis (RA) provide an important opportunity for understanding care of patients with a serious chronic condition. OBJECTIVES: We sought to characterize the complexity of care for patients with RA, including metrics describing the patient, the disease, and use of the health care system across time and place. METHODS: We undertook a prospective cohort study of 568 community-dwelling patients with RA by using observational data from clinically detailed telephone interviews at baseline and 2 years later in addition to medical record abstraction. Health status, comorbidity, use of disease-modifying antirheumatic drugs, visits, providers, provider types, encounter settings, and the discontinuity between patients and providers were studied. RESULTS: Within a 12-month window, 568 patients had 8686 outpatient encounters with the health care system with a mean of 3.41 unique providers per patient associated with a mean of 5 primary care and 6 rheumatologist visits. Half did not see a primary care physician, and 20% did not see a rheumatologist during 6-month periods despite their use of potentially toxic drugs, a mean of 4 comorbidities and progressive RA. Over the course of 24 months, 29% of patients changed their primary care provider, and 15% changed their rheumatologist. Patients were moderately impaired with mean SF-12 physical component score 37 (SD, 9). CONCLUSION: Patients with RA have frequent encounters with multiple providers and also frequent discontinuity of care. Recognizing the complexity of the care of patients with a chronic disease across multiple dimensions provides an opportunity to better understand challenges and opportunities in delivering high quality care. PMID- 17279022 TI - The utility of administrative data for measuring adherence to cancer surveillance care guidelines. AB - BACKGROUND: Adherence to professional society guidelines for follow-up or surveillance care in cancer survivors usually is measured with medical record review. Administrative data represent an alternative approach that may encompass larger numbers of patients with relatively low incremental costs. OBJECTIVES: We sought to determine the feasibility of using claims data to measure guideline adherence. METHODS: By reviewing paper and electronic medical records and claims data of 429 patients with 1 of 5 common cancers who received treatment with curative intent, we compared specific procedure receipt as well as guideline adherence classification as derived from claims and medical record data. Concordance was measured via kappa statistics. MEASURES: Care in the initial 18 month follow-up period was characterized as less than recommended, recommended, or greater than recommended per practice guidelines in both medical record and administrative data. RESULTS: Matching rates for individual procedures varied and were generally highest for certain laboratory tests and lowest for physical examinations. There were generally good-to-excellent levels of agreement (kappa=0.34-0.96) between a patient's classification in claims data and medical record data. No consistent differences in agreement were observed according to insurance type. CONCLUSIONS: In general, claims data capturing procedures and visit use for characterizing guideline adherence was comparable with what was documented in the medical record and suggests that if validated in other settings, administrative data could be used to describe patterns of follow up care. PMID- 17279023 TI - Measuring performance directly using the veterans health administration electronic medical record: a comparison with external peer review. AB - BACKGROUND: Electronic medical records systems (EMR) contain many directly analyzable data fields that may reduce the need for extensive chart review, thus allowing for performance measures to be assessed on a larger proportion of patients in care. OBJECTIVE: This study sought to determine the extent to which selected chart review-based clinical performance measures could be accurately replicated using readily available and directly analyzable EMR data. METHODS: A cross-sectional study using full chart review results from the Veterans Health Administration's External Peer Review Program (EPRP) was merged to EMR data. RESULTS: Over 80% of the data on these selected measures found in chart review was available in a directly analyzable form in the EMR. The extent of missing EMR data varied by site of care (P<0.01). Among patients on whom both sources of data were available, we found a high degree of correlation between the 2 sources in the measures assessed (correlations of 0.89-0.98) and in the concordance between the measures using performance cut points (kappa: 0.86-0.99). Furthermore, there was little evidence of bias; the differences in values were not clinically meaningful (difference of 0.9 mg/dL for low-density lipoprotein cholesterol, 1.2 mm Hg for systolic blood pressure, 0.3 mm Hg for diastolic, and no difference for HgbA1c). CONCLUSIONS: Directly analyzable data fields in the EMR can accurately reproduce selected EPRP measures on most patients. We found no evidence of systematic differences in performance values among these with and without directly analyzable data in the EMR. PMID- 17279024 TI - Self-rated health among foreign- and U.S.-born Asian Americans: a test of comparability. AB - OBJECTIVES: We investigated differences between foreign- and U.S.-born Asian Americans in self-rating their physical and mental health. In particular, we tested whether the foreign-born respondents underreport the extreme categories of the scale as compared with U.S.-born respondents. METHODS: We analyzed data from the National Latino and Asian American Study to examine whether immigrants are less likely to use the extreme ends of the 5-category self-rated health scales than their U.S.-born counterparts. We used propensity score matching to derive groups of U.S.- and foreign-born Asian Americans who share similar demographic and health characteristics. We defined propensity scores as predicted probabilities of being U.S. born, given individual background characteristics. The propensity score framework allowed us to make descriptive comparisons of self rated health responses controlling for background characteristics. We used log linear symmetry models to examine cross-tabulations of self-rated physical and mental health reports in matched pairs by the 2 (extreme and nonextreme) and 5 ("excellent," "very good," "good," "fair," and "poor") categories. RESULTS: Controlling for background characteristics, we found no evidence that foreign born Asian Americans are less likely to endorse extreme categories in self-rated physical or mental health than U.S.-born Asian Americans, as well as no evidence of imbalances in endorsement of any particular self-rated health category between the 2 groups. CONCLUSIONS: Controlling for demographic and health characteristics, we find no systematic differences between foreign- and U.S.-born Asian Americans in reporting self-rated physical and mental health on the 5 category scales from "excellent" to "poor." PMID- 17279026 TI - Conflicts and concordance between measures of medication prescribing quality. AB - BACKGROUND: Several instruments commonly are used to assess the quality of medication prescribing. However, little is known about the relationship between these instruments or the concordance of their quality assessments when applied to the same group of patients. METHODS: We assessed 3 indicators of prescribing quality in a cohort of 196 veterans age 65 and older who were taking 5 or more medications. These 3 indicators assessed whether each patient was (1) taking any medication from the drugs-to-avoid criteria of Beers et al, (2) taking any medication with a score of 3 or more on the Medication Appropriateness Index (MAI), and/or (3) taking 9 or more medications (polypharmacy). Kappa statistics were used to assess agreement between measures. RESULTS: Mean age was 74.6 years, and patients used a mean of 8.1 medications. Six percent of drugs were rated inappropriate by the Beers drugs-to-avoid criteria, whereas 23% of drugs received an MAI score of 3 or more. Overall agreement between these metrics was 78%, little more than expected by chance (kappa statistic 0.14, P<0.01). At the level of the patient, the proportion of subjects taking one or more inappropriate drugs was 37% by drugs-to-avoid criteria and 82% by MAI, whereas 37% had polypharmacy of >or=9 drugs. Prescribing was classified as inappropriate by all 3 metrics in 18% of patients and as appropriate by all 3 metrics in 13%. Together, this level of agreement was slightly better than chance (3-way kappa statistic 0.08, P=0.03). Agreement remained low in sensitivity analyses using different cutoffs for the Beers criteria, a range of thresholds for MAI scores, and different definitions of polypharmacy, with kappa statistics300 micromol/L) progress to end stage renal disease. DESIGN: Retrospective analysis of laboratory data and chart review. SETTING: Queen's University Family Medicine Centre in Kingston, Ont. PARTICIPANTS: All patients who had SC levels measured at a nearby hospital laboratory between January 1994 and December 1998. MAIN OUTCOME MEASURES: Recently recorded height and weight measurements, latest SC measurements (if available), whether patients had been referred to nephrologists, comorbidity, medications being taken, whether patients were currently undergoing dialysis or had received a renal transplant, and whether patients had died. RESULTS: In the 1434 charts of eligible patients, 64 (4.5%) had elevated initial SC levels (>130 micromol/L) recorded, and 57 of these contained follow-up SC levels also. Among these 57 patients, 32 (56%) saw their SC levels return to normal, including 50% of those whose initial levels had been >300 micromol/L. Only 7 patients (12%) with elevated SC levels progressed to higher levels during the follow-up period. Average age in the study group was 63 years; those with initial elevated SC levels were older than the average (70 years). CONCLUSION: More than half of those with initially elevated SC levels (>130 micromol/L) saw their levels return to normal, including patients whose initial levels had been >300 micromol/L. It seems that a single elevated SC measurement does not predict ongoing decline in renal function. PMID- 17279187 TI - Reasons for ordering spinal x-ray investigations: how they influence general practitioners' management. AB - OBJECTIVE: To explore whether general practitioners who request spinal x-ray investigations are less likely to refer, prescribe medication, or order additional tests when they intend only to reassure patients rather than to exclude or confirm disease. DESIGN: Cross-sectional survey. Physicians recorded reasons for requesting x-ray examinations and differential diagnoses on the request form. When they received a radiologist's report on a spinal x-ray test, GPs also received a questionnaire on their subsequent management. SETTING: Maastricht region of the Netherlands. PARTICIPANTS: All 90 GPs in the Maastricht region who referred patients for spinal x-ray examinations during 19 consecutive weeks. MAIN OUTCOME MEASURES: Reason for requesting spinal x-ray investigations, results, and subsequent management. RESULTS: We received completed questionnaires on 386 patient contacts. Physicians were significantly less likely to refer, prescribe medication, or order additional tests when they intended only to reassure patients rather than to exclude or confirm disease (odds ratio 0.3, 95% confidence interval 0.1 to 0.6). This effect was independent of the results of the x-ray examinations. CONCLUSION: Physicians seem to be aware that they have requested spinal x-ray examinations only to reassure patients, and they account for this in their management. These findings support debate on the negative consequences of requesting tests for other than purely medical reasons. Concerns about unjustified actions based on the results of x-ray examinations that were requested primarily to reassure patients should probably have only a minor role in the debate about unnecessary testing. PMID- 17279188 TI - Maternal serum screening in Newfoundland and Labrador: do attitude and knowledge affect physicians' practice? AB - OBJECTIVE: To examine family physicians' practice of, attitudes toward, and knowledge about maternal serum screening (MSS) and to compare the demographic and practice characteristics, attitudes, and knowledge of physicians who offer MSS to all their pregnant patients with those of physicians who offer MSS to some or none of their pregnant patients. DESIGN: Cross-sectional mailed survey. SETTING: Newfoundland and Labrador. PARTICIPANTS: One hundred eighty-two family physicians who provided prenatal care. MAIN OUTCOME MEASURES: Proportion of physicians offering MSS to their pregnant patients. Sociodemographic characteristics and attitudes toward and knowledge about MSS of physicians who offer MSS to all, some, or none of their pregnant patients. RESULTS: Just over half the physicians (52.2%) offered MSS to all their pregnant patients, 34.6% offered it to some patients, and 13.2% did not offer MSS at all. Almost two thirds of physicians (63.6%) had not changed their practice regarding MSS in the past 18 months, but 29.5% said they offered MSS more often. About 69.6% of physicians communicated positive results to patients within 48 hours; 60.8% communicated negative results at the next clinical appointment. Half (50.6%) believed that offering MSS did not affect their legal risk, 24.1% said it increased their risk, and 25.3% said it decreased their risk. Most physicians (83.4%) ordered MSS at the correct gestational age. A larger proportion of those who offered MSS to all patients were female, were between 30 and 39 years old, had graduated from Canadian medical schools, practised in urban centres, and were aware of the provincial MSS program. Physicians who offered MSS to all, some, or none of their patients were similar in terms of length of practice in Canada, whether they performed deliveries, number of pregnant women they cared for annually, beliefs about MSS and legal risk, and general knowledge of MSS detection rates. CONCLUSION: More than half the family physicians in Newfoundland and Labrador offered MSS to all their pregnant patients, and another third offered it to some patients. Physicians' practice was not related to their attitudes toward or knowledge about MSS. PMID- 17279190 TI - Following treatment guidelines for developmentally disabled adults. The invisible 3%. PMID- 17279191 TI - At a crossroads: the future of comprehensive care in Canada. PMID- 17279192 TI - Attention deficit hyperactivity disorder: yes, really. PMID- 17279193 TI - Compliance with prenatal vitamins. Patients with morning sickness sometimes find it difficult. AB - QUESTION: Many pregnant patients cannot tolerate multivitamins because of morning sickness. Is it the tablet size or the iron content that causes the problems, and what can be done? ANSWER: Recent Motherisk studies have shown both tablet size and high iron content to be associated with lower compliance among women with morning sickness. It does appear that tablet size is more likely to affect compliance. Some new multivitamin tablets are smaller, and some have less iron content. PMID- 17279194 TI - Dermacase. Molluscum contagiosum. PMID- 17279195 TI - Ondansetron for acute gastroenteritis in children. AB - QUESTION: In my pediatric practice I see many children with acute gastroenteritis. Their parents ask for antiemetic medications. Ondansetron has been well tolerated when used to control nausea and vomiting in patients receiving chemotherapy. Is there a role for it in managing acute gastroenteritis in children? ANSWER: Use of antiemetics is not indicated for treatment of acute gastroenteritis. Some evidence suggests ondansetron is clinically more effective and better tolerated and has a better side effect profile than other antiemetics, but does not suggest that it reduces hospital admission rates. Use of ondansetron, as with other antiemetics, continues to be at treating physicians' discretion, and potential adverse events should be considered before administration. PMID- 17279196 TI - Doctor-patient communication. Time to talk. PMID- 17279197 TI - Practice tips. Knee joint injections and aspirations: the triangle technique. PMID- 17279198 TI - Consensus guidelines for primary health care of adults with developmental disabilities. AB - OBJECTIVE: To develop practical Canadian guidelines for primary health care providers based on the best available evidence for addressing health issues in adults with developmental disabilities (DD). QUALITY OF EVIDENCE: Authors of background papers synthesized information from their own clinical experience, from consultations with other experts, and from relevant professional publications. Based on discussions of these papers at a colloquium of knowledgeable health care providers, a consensus statement was developed. Standard criteria were used to select guidelines for consideration and to rank evidence supporting them. Most evidence was level III. MAIN MESSAGE: People with DD have complex health issues, some differing from those of the general population. Adequate primary health care is necessary to identify these issues and to prevent morbidity and premature death. Physical, behavioural, and mental health difficulties should be addressed, and primary health care providers should be particularly attentive to the interactions of biological, psychological, and social factors contributing to health, since these interactions can easily be overlooked in adults with DD. Attention must also be paid to such ethical issues as informed consent and avoidance of harm. Developmental disabilities are not grounds for care providers to withhold or to withdraw medically indicated interventions, and decisions concerning such interventions should be based on patients' best interests. CONCLUSION: Implementing the guidelines proposed here would improve the health of adults with DD and minimize disparities in health and health care. PMID- 17279199 TI - Managing the misplaced: approach to endometriosis. AB - OBJECTIVE: To review the presentation of endometriosis, steps to diagnosis, and medical and surgical management options. SOURCES OF INFORMATION: MEDLINE was searched from January 1996 to November 2004, EMBASE from January 1996 to January 2005, and the Cochrane Database of Systematic Reviews for the 4th quarter of 2004. MAIN MESSAGE: Endometriosis is a common, progressive disease with an estimated prevalence of 10%. It can cause dyspareunia, dysmenorrhea, low back pain, and infertility. It can be diagnosed on clinical grounds and treated without laparoscopy provided pregnancy is not desired. First- and second-line medical treatments are nonsteroidal anti-inflammatory drugs, combined oral contraceptive pills, progestins, gonadotropin-releasing hormone agonists, and androgens. Surgical options should be considered when these medications are ineffective or if pregnancy is desired. CONCLUSION: Family physicians have an important role in diagnosing and treating women with endometriosis. PMID- 17279201 TI - Approach to managing patients with sulfa allergy: use of antibiotic and nonantibiotic sulfonamides. AB - OBJECTIVE: To present an approach to use of sulfonamide-based (sulfa) medications for patients with sulfa allergy and to explore whether sulfa medications are contraindicated for patients who require them but are allergic to them. SOURCES OF INFORMATION: A search of current pharmacology textbooks and of MEDLINE from 1966 to the present using the MeSH key words "sulfonamide" and "drug sensitivity" revealed review articles, case reports, one observational study (level II evidence), and reports of consensus opinion (level III evidence). MAIN MESSAGE: Cross-reactivity between sulfa antibiotics and nonantibiotics is rare, but on occasion it can affect the pharmacologic and clinical management of patients with sulfa allergy. CONCLUSION: How a physician approaches using sulfa medications for patients with sulfa allergy depends on the certainty and severity of the initial allergy, on whether alternatives are available, and on whether the contemplated agent belongs to the same category of sulfa medications (ie, antibiotic or nonantibiotic) as the initial offending agent. PMID- 17279200 TI - Cancers related to genetic mutations: important psychosocial issues for Canadian family physicians. AB - OBJECTIVE: To review psychosocial issues family physicians might wish to be aware of when discussing genetic testing for predisposition for cancer with their patients. QUALITY OF EVIDENCE: Articles from academic journals were reviewed. Studies provided level II and III evidence. MAIN MESSAGE: Family physicians should be prepared to explore their patients' decisions for or against genetic testing, as well as to discuss the possible outcomes of a decision to test. While genetic testing has many potential benefits, patients are at risk of having psychosocial problems at many stages in a genetic testing inquiry. To minimize these problems, family physicians should discuss motivation for testing and the potential psychosocial effect of both deciding to undergo and deciding to forgo genetic testing for cancer-related genes. Also important are deciding whether patients qualify for the tests; coping with the waiting period before testing can be done; and discussing positive, negative, and inconclusive outcomes of testing. CONCLUSION: Family physicians are likely in the best position to discuss genetic testing for predisposition for cancer with their patients given their knowledge of both the tests and their patients' ability to cope with testing. PMID- 17279202 TI - Adolescent care. Part 1: are family physicians caring for adolescents' mental health? AB - OBJECTIVE: To investigate how often family physicians see adolescents with mental health problems and how they manage these problems. DESIGN: Mailed survey completed anonymously. SETTING: Province of Quebec. PARTICIPANTS: All 358 French speaking family physicians who practise primarily in local community health centres (CLSCs), including physicians working in CLSC youth clinics, and 749 French-speaking practitioners randomly selected from private practice. MAIN OUTCOME MEASURES: Frequency with which physicians saw adolescents with mental health problems, such as depression, suicidal thoughts, behavioural disorders, substance abuse, attempted suicide, or suicide, during the last year or since they started practice. RESULTS: Response rate was 70%. Most physicians reported having seen adolescents with mental health problems during the last year. About 10% of practitioners not working in youth clinics reported seeing adolescents with these disorders at least weekly. Anxiety was the most frequently seen problem. A greater proportion of physicians working in youth clinics reported often seeing adolescents for all the mental health problems examined in this study. Between 8% and 33% of general practitioners not working in youth clinics said they had not seen any adolescents with depression, behavioural disorders, or substance abuse. More than 80% of physicians had seen adolescents who had attempted suicide, and close to 30% had had adolescent patients who committed suicide. CONCLUSION: Family physicians play a role in adolescent mental health care. The prevalence of mental health problems seems higher among adolescents who attend youth clinics. Given the high prevalence of these problems during adolescence, we suggest on the basis of our results that screening for these disorders in primary care could be improved. PMID- 17279203 TI - Adolescent care. Part 2: communication and referral practices of family physicians caring for adolescents with mental health problems. AB - OBJECTIVE: To document with whom family physicians communicate when evaluating adolescents with mental health problems, to whom they refer these adolescents, and their knowledge and perceptions of the accessibility of mental health services in their communities. DESIGN: Mailed survey completed anonymously. SETTING: Province of Quebec. PARTICIPANTS: All general practitioners who reported seeing at least 10 adolescents weekly (n = 255) among 707 physicians who participated in a larger survey on adolescent mental health care in general practice. MAIN OUTCOME MEASURES: Whether family physicians communicated with people (such as parents, teachers, or school nurses) when evaluating adolescents with mental health problems. Number of adolescents referred to mental health services during the last year. Knowledge of mental health services in the community and perception of their accessibility. RESULTS: When asked about the last 5 adolescents seen with symptoms of depression or suicidal thoughts, depending on type of practice, 9% to 19% of physicians reported routinely communicating with parents, and 22% to 32% reported not contacting parents. Between 16% and 43% of physicians referred 5 adolescents or fewer to mental health services during a 12-month period. Most practitioners reported being adequately informed about the mental health services available in their local community clinics. Few physicians knew about services offered by private-practice psychologists, child psychiatrists, or community groups. Respondents perceived mental health services in community clinics (CLSCs) as the most accessible and child psychiatrists as the least accessible services. CONCLUSION: Few physicians routinely contact parents when evaluating adolescents with serious mental health problems. Collaboration between family physicians and mental health professionals could be improved. The few referrals made to mental health professionals might indicate barriers to mental health services that could mean many adolescents do not receive the care they need. The lack of access to mental health services, notably to child psychiatrists, reported by most respondents could explain why some physicians choose not to refer adolescents. PMID- 17279204 TI - Care pathways in early rheumatoid arthritis. AB - OBJECTIVE: To determine the proportion of family physicians who diagnose rheumatoid arthritis (RA) correctly and to note how they report they would manage RA patients. DESIGN: Mailed survey (self-administered questionnaire) requesting comments on vignettes. SETTING: Province of Quebec. PARTICIPANTS: Computer generated random sample of family physicians registered with the Quebec College of Family Physicians. MAIN OUTCOME MEASURES: The proportion of family physicians who recognized RA and their reported management strategies. RESULTS: Most respondents recognized the vignette presentation as a case of RA; 133/138 (96.4%) indicated RA as their provisional diagnosis, and all but 1 of the remaining respondents listed RA as a differential diagnosis. Of those who considered RA as a provisional or possible diagnosis, 107 (77.5% of all respondents) suggested referring the patient to a rheumatologist. Among the physicians who suggested referral, none indicated they would initiate disease-modifying antirheumatic drugs (DMARDs). CONCLUSION: Almost all respondents considered RA as a provisional or differential diagnosis. Although many suggested referring the patient to a rheumatologist, almost a quarter did not. Initiating DMARDs before referring patients to rheumatologists appears to be rare. Since DMARDs given during the early stages of RA are known to decrease damage and dysfunction, ways to increase their use and optimize care pathways for new-onset inflammatory arthritis are urgently needed. PMID- 17279205 TI - Young adults' experiences with cancer: comments from patients and survivors. AB - OBJECTIVE: To examine the experiences with cancer of adults diagnosed when between 20 and 35 years old. DESIGN: Qualitative study using semistructured interviews. SETTING: Largest health care region in the province of New Brunswick. PARTICIPANTS: Six men and 9 women cancer patients and survivors. METHOD: Fifteen adults interviewed when between the ages of 20 and 43 representing a variety of cancers and stages of disease were recruited for this study. Interviews were guided by a set of open-ended questions and explored participants' experiences with cancer from initial presentation of symptoms through to survivorship issues. MAIN FINDINGS: The most important clinical issue that emerged from the analysis was that participants' youth appeared to contribute to delays in diagnosis of cancer. These delays were attributed to either patients' or physicians' inaction. Some patients attributed their initial cancer symptoms to the adverse effects of alcohol or excessive partying; others feared a bad diagnosis and delayed seeking help. Family physicians frequently interpreted nonspecific symptoms as resulting from patients' lifestyle choices and were reluctant to consider a diagnosis of cancer. Several family physicians reportedly believed that persistent symptoms could not be the result of cancer because patients were too young. CONCLUSION: Although cancer is relatively rare in young adults, family physicians need to include it in differential diagnoses. Both patients and physicians tend to minimize cancer symptoms in young adults. Delays in diagnosis might not affect health outcomes, but can cause distress to young adults with cancer. PMID- 17279207 TI - Laboratories of primary care: practice-based research networks in Canada. PMID- 17279208 TI - Should women 40 to 49 years of age be offered mammographic screening? PMID- 17279209 TI - What is adequate? PMID- 17279210 TI - Chest pain, dyspnea, and cough. PMID- 17279211 TI - Clarifying omega-3 fatty acid recommendations. PMID- 17279212 TI - Clarifying omega-3 fatty acid recommendations. PMID- 17279213 TI - Exposure to alcohol-containing medications during pregnancy. AB - QUESTION: A pregnant patient consulted her physician after discovering that a diphenhydramine preparation (Benadryl elixir) she used for allergy symptoms during the first trimester of her pregnancy contained 15% alcohol. Should she be concerned about fetal alcohol spectrum disorder in her baby? ANSWER: Most ethanol containing medical preparations are safe during pregnancy. Adult doses of some elixirs with high ethanol concentrations might produce blood levels similar to those achieved by drinking 1 alcoholic beverage. Caution is advisable when prescribing ethanol-containing elixirs to pregnant women, as is informing them about the alcohol content. PMID- 17279214 TI - Ophthaproblem. Choroidal rupture. PMID- 17279215 TI - Dermacase. Psoriasis. PMID- 17279216 TI - Practice tips. E-mailing patients. PMID- 17279217 TI - Benign prostatic hypertrophy: update on drug therapy. PMID- 17279218 TI - Misuse of and dependence on opioids: study of chronic pain patients. AB - OBJECTIVE: To review the evidence on identifying and managing misuse of and dependence on opioids among primary care patients with chronic pain. QUALITY OF EVIDENCE: MEDLINE was searched using such terms as "opioid misuse" and "addiction." The few studies on the prevalence of opioid dependence in primary care populations were based on retrospective chart reviews (level II evidence). Most recommendations regarding identification and management of opioid misuse in primary care are based on expert opinion (level III evidence). MAIN MESSAGE: Physicians should ask all patients receiving opioid therapy about current, past, and family history of addiction. Physicians should take "universal precautions" that include careful prescribing and ongoing vigilance for signs of misuse. Patients suspected of opioid misuse can be treated with a time-limited trial of structured opioid therapy if they are not acquiring opioids from other sources. The trial should consist of daily to weekly dispensing, regular urine testing, and tapering of doses of opioids. If the trial fails or is not indicated, patients should be referred for methadone or buprenorphine treatment. CONCLUSION: Misuse of and dependence on opioids can be identified and managed successfully in primary care. PMID- 17279220 TI - Gastroprotective strategies among NSAID users: guidelines for appropriate use in chronic illness. AB - OBJECTIVE: To review proper use of gastroprotective strategies in family medicine for patients requiring chronic nonsteroidal anti-inflammatory drug (NSAID) therapy. QUALITY OF EVIDENCE: Evidence of the efficacy and safety of strategies currently in use (prostaglandin analogues, cyclooxygenase-2 inhibitors, proton pump inhibitors) is derived from randomized controlled trials (level I evidence). The simultaneous use of multiple medications for very high-risk NSAID users is supported only by expert opinion (level III evidence). MAIN MESSAGE: Gastroprotective strategies should be reserved for NSAID users at substantially increased risk of gastrointestinal complications; low-risk patients can safely use NSAIDs alone. Cyclooxygenase-2 inhibitors, prostaglandin analogues, and proton pump inhibitors reduce the risk of NSAID-related gastointestinal complications by 40% to 90%. Cyclooxygenase-2 inhibitors should be avoided by patients who have or are at risk for cardiovascular disease. CONCLUSION: Chronic NSAID use has been implicated in the development of severe and potentially life threatening gastointestinal complications, though certain strategies are known to decrease the risk of these NSAID-related gastointestinal complications. Prescribing physicians must know which of their patients should be prescribed medications and which strategies are appropriate for particular patients. PMID- 17279221 TI - Future practice location and satisfaction with rural medical education: survey of medical students. AB - OBJECTIVE: To explore the desired future practice location of a cohort of medical students with strong rural representation and to inquire whether they were satisfied with their medical experiences in rural primary care settings. DESIGN: Survey questionnaire. SETTING: The College of Medicine at the University of Saskatchewan in Saskatoon. PARTICIPANTS: One hundred twenty-two medical students. MAIN OUTCOME MEASURES: Demographic information, plans for future practice, and opinions on rural medical experiences in primary care settings. RESULTS: Although students from both rural and non-rural backgrounds were highly satisfied with mandatory and voluntary rural experiences and considered them valuable for their medical education, fewer than 10% of the 122 students desired to work in centres with less than 10 000 population. Only 2 students hoped to practise in such locations. Most students interested in family practice were interested in urban practice, and most students from rural areas were not interested in rural practice. CONCLUSION: Both rural and non-rural students were highly satisfied with their medical education in rural primary care settings, but this did not mean either group wanted to practise in rural settings. Demographic profiling of students (to ascertain whether they have rural origins) and assessing satisfaction with rural medical education give only partial information on who might choose to practise family medicine in rural areas. PMID- 17279219 TI - Opioids for managing chronic non-malignant pain: safe and effective prescribing. AB - OBJECTIVE: To review the evidence on safe and effective prescribing of opioids for chronic non-malignant pain. QUALITY OF EVIDENCE: MEDLINE was searched using the terms "opioid effectiveness" and "adverse effects." There is strong evidence that opioids are effective for both nociceptive and neuropathic pain, but limited evidence that they are effective for pain disorder. There is little information on their effectiveness at high doses or on the adverse effects of high doses. MAIN MESSAGE: Opioids should be initiated after an adequate trial of acetaminophen or nonsteroidal anti-inflammatory drugs for nociceptive pain and of tricyclic antidepressants or anticonvulsants for neuropathic pain. Patients should be asked to sign treatment agreements and to give informed consent to treatment. Patients should experience a graded analgesic response with each dose increase. Titrate doses of immediate-release opioids slowly upward until pain reduction is achieved, and then switch patients to controlled-release opioids. Most patients with chronic non-malignant pain can be managed with<300 mg/d of morphine (or equivalent). CONCLUSION: Opioids are safe and effective for managing chronic pain. PMID- 17279222 TI - Management of dementia by family physicians in academic settings. AB - OBJECTIVE: To determine what proportion of patients with dementia seen by family physicians are assessed and managed according to the recommendations of the Canadian Consensus Conference on Dementia (CCCD). DESIGN: Retrospective medical record review. SETTING: Outpatient services in university-affiliated family practice clinics in Calgary, Alta; Ottawa, Ont; and Toronto, Ont. PARTICIPANTS: One hundred sixty patients who were diagnosed with dementia between January 1, 2000, and June 1, 2004. MAIN OUTCOME MEASURES: Use of the Mini-Mental State Examination (MMSE); collateral history; physical examination maneuvers; initial laboratory tests; diagnostic imaging; caregiver identification, assessment, and referral; driving assessment; specialist referral patterns; and other recommendations of the CCCD. RESULTS: The average age of patients assessed was 83 years; most patients (66.3%) were female. More than half (54.1%) were diagnosed with Alzheimer disease or vascular dementia. More than 25% of patients were not given a specific diagnosis: 13.1% were labeled as "dementia," and 12.5% as "not yet diagnosed." For most patients (69.6%) a collateral history was obtained and a primary caregiver identified (79.4%). Few physicians, however, assessed caregiver stress (33.1%) or referred caregivers for support (12.5%). Most patients (80.6%) seen by their family physicians for cognitive changes underwent at least one MMSE. The average score on the first MMSE was 23.5 (of 30) points. Most physicians ordered appropriate "basic" blood tests as part of their assessment. Forty percent of patients had computed tomographic examinations within 3 months of reporting symptoms of cognitive difficulties to their family physicians. Of these, 25% met the criteria for computed tomographic scan as recommended by the guidelines. Only 36.5% were asked about driving status or safety concerns and had this inquiry documented. Of those, 15.5% were referred for driving evaluations and 12.5% were reported to the Ministry of Transportation. CONCLUSION: There is fair to good compliance with recommendations of the 1999 CCCD guidelines. There is, however, little assessment of caregiver coping and referral of caregivers for support. Similarly, there is little assessment of driver safety and referral for formal driving evaluations. Computed tomographic imaging as part of the evaluation of dementia is overused. PMID- 17279225 TI - Queue jumping: social justice and the doctor-patient relationship. PMID- 17279223 TI - Promoting best practices for control of respiratory infections: collaboration between primary care and public health services. AB - OBJECTIVE: To determine the effectiveness of a short-term intervention to promote best practices for control of respiratory infections in primary care physicians' offices. DESIGN: Before-after observational study. SETTING: Family physicians' offices in Ottawa, Ont. PARTICIPANTS: General practitioners and office staff. INTERVENTIONS: Four infection-control practices (use of masks, alcohol-based hand gel, and signs, and asking patients to sit at least 1 m apart in the waiting room) were observed, and 2 reported infection-control practices (disinfecting surfaces and use of hand-gel dispensers in examining rooms) were audited before the intervention and 6 weeks after the intervention. MAIN OUTCOME MEASURES: Percentage of patients asked to use masks and alcohol-based hand gel, number of relevant signs, and percentage of patients asked to sit at least 1 m away from other patients. Percentage of surfaces disinfected and percentage of physicians using hand-gel dispensers in examining rooms. RESULTS: Of 242 practices invited, 53 agreed to participate (22% response rate), and within those practices, 143/151 (95%) physicians participated. Signs regarding respiratory infection control measures increased from 15.4% to 81.1% following the intervention (P < .001). At least 1 patient with cough and fever was given a mask in 17% of practices before the intervention; during the observation period after the intervention, at least 1 patient was given a mask in 66.7% of practices (P < .001). Patients were instructed to use alcohol-based hand gel in 24.5% of practices before the intervention and in 79.2% of practices after it (P < .001). Instruction to sit at least 1 m from others in the waiting area was given in 39.6% of practices before the intervention and in 52.8% of practices following the intervention (P < .001). Before the intervention, the percentage of practices using all 4 audited primary prevention measures was 3.8%; after the intervention, 52.8% of practices were using them (P < .001), demonstrating a 49% increase in adoption of best practices. CONCLUSION: A multifaceted intervention by public health nurses successfully promoted best practices for control of respiratory infections in primary care offices. Collaboration between public health services and primary care can promote best practices and warrants further study and development in areas of common interest. PMID- 17279226 TI - Is there a role for marijuana in medical practice? PMID- 17279228 TI - E-mail guidelines. PMID- 17279229 TI - Shared objections to NAOMI. PMID- 17279230 TI - Functional medicine. PMID- 17279231 TI - Does chronic opioid use really reduce pain? PMID- 17279232 TI - Preventing recurrence of severe morning sickness. AB - QUESTION: A recent Motherisk article showed that initiating antinauseants even before symptoms start could prevent recurrence of severe morning sickness. In the study described, however, different physicians used different drugs. How can one be sure which drugs work? ANSWER: The study of 26 women who had had severe morning sickness during previous pregnancies showed that using antiemetics before symptoms of morning sickness started appeared to prevent recurrence of severe morning sickness in subsequent pregnancies. Physicians in the United States used various antinauseant drugs. Physicians in Canada administered only one drug, the combination of doxylamine-pyridoxine (Diclectin), to 12 women. Subanalysis of these 12 women revealed that pre-emptive use of doxylamine-pyridoxine significantly decreased the likelihood that severe morning sickness would recur. PMID- 17279233 TI - Dermacase. Atrophic patches. PMID- 17279234 TI - Practice Tips. Clinical sign could screen for depressive symptoms. PMID- 17279235 TI - As simple as ABCD: identifying patients at high risk of stroke soon after a transient ischemic attack. PMID- 17279236 TI - Below the belt: approach to chronic pelvic pain. AB - OBJECTIVE: To present a practical approach to the symptom complex called chronic pelvic pain (CPP). Chronic pelvic pain is defined as nonmenstrual pain lasting 6 months or more that is severe enough to cause functional disability or require medical or surgical treatment. SOURCES OF INFORMATION: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched from January 1996 to December 2004. MAIN MESSAGE: While the source of pain in CPP can be gynecologic, urologic, gastrointestinal, musculoskeletal, or psychoneurologic, 4 conditions account for most CPP: endometriosis, adhesions, interstitial cystitis, and irritable bowel syndrome. More than one source of pain can be found in the same patient. Management involves treating the underlying condition, the pain itself, or both. Nonnarcotic analgesics are first-line therapy for pain relief; hormonal therapies are beneficial if the pain has a cyclical component. A multidisciplinary approach addressing environmental factors and incorporating medical management with physiotherapy, psychotherapy, and dietary modifications works best. CONCLUSION: Although caring for patients with CPP can be challenging and frustrating, family physicians are in an ideal position to manage and coordinate their care. PMID- 17279238 TI - Family physicians' reactions to performance assessment feedback. AB - OBJECTIVE: To explore and describe family physicians' personal and professional responses to performance assessment feedback. DESIGN: Qualitative study using one on-one semistructured interviews after feedback on performance. SETTING: Fee-for service family practices in eastern Ontario. PARTICIPANTS: Eight physicians out of 25 physicians in the control group of a previous randomized controlled trial who received performance assessment feedback were purposefully selected using maximum variation sampling to represent various levels of performance. Five female physicians (2 part-time and 3 full-time) and 3 male physicians (all full time) were interviewed. These physicians had practised family medicine for an average of 18.5 years (range 9 to 32 years). METHOD: Semistructured one-on-one interviews were conducted to determine what physicians thought and felt about their private feedback sessions and to solicit their opinions on performance assessment in general. Information was analyzed using an open coding style and a constant comparative method of analysis. MAIN FINDINGS: Two major findings were central to the core elements of medical professionalism and perceived accountability. Physicians indicated that the private feedback they received was a valuable and necessary part of medical professionalism; however, they were reluctant to share this feedback with patients. Physicians described various layers of accountability from the most important inner layer, patients, to the least important outer layer, those funding the system. CONCLUSION: Performance feedback was viewed as important to family physicians for maintaining medical professionalism and accountability. PMID- 17279241 TI - Inorganic materials from ionic liquids. AB - Ionic liquids (ILs) can add value to many chemical processes. The electrochemistry and the (physical) organic chemistry communities in particular have extensively studied the structure, properties, and reactivities of various ILs and reactions therein. Inorganic and materials chemists are the newest addition to the IL community: over a number of years, various approaches to the fabrication of inorganic solids with unprecedented and sometimes unique structures and properties have been reported. This article summarizes the state of this particular sub-field of IL research and highlights a few promising approaches that not only reproduce conventional synthesis in ILs, but that provide pathways towards new, possibly unknown, inorganics with advantageous properties that cannot (or only with great difficulty) be made via conventional processes. PMID- 17279239 TI - Primum non nocere: could the health care system contribute to suffering? In-depth study from the perspective of terminally ill cancer patients. AB - OBJECTIVE: To explore terminally ill patients' perceptions of their own suffering in order to describe, from these patients' perspective, some elements of health care providers' response to suffering. DESIGN: Qualitative study using content analysis methods suited to a grounded theory approach. SETTING: Teaching and nonteaching hospital oncology clinics, palliative care services (both ambulatory and in-unit), and family practices. PARTICIPANTS: Twenty-six patients diagnosed with terminal cancer. METHODS: Interviews were audiotaped and transcribed verbatim. Data from each interview were coded and categorized to identify and define themes. Themes were discussed and refined until those rating them agreed on them. Data were collected until saturation of emerging issues was reached. MAIN FINDINGS: In our health care system, patients are caught in a pervasive pattern of suffering avoidance, which in turn contributes to increased suffering. Health care services are perceived as a battlefield where physicians and patients are engaged in a losing struggle to ward off illness and death. Both physicians and patients engage in avoiding skepticism and muffling distress. The unavoidable avowal of powerlessness in the face of terminal disease is perceived as capitulation and therapeutic abandonment. Budgetary restraints and understaffing, along with a pervasive culture that implicitly denies death, produce an environment conducive to the avoidance of suffering. To counter this, health care practices that foster increased overlap and continuity between the spheres of oncology, palliative care, and family medicine seem worth developing. CONCLUSION: The suffering of gravely ill patients might be hard to alleviate in the context of modern health care organizations. In some cases, health care delivery directly contributes to increased suffering. Providing support while also helping patients and their families to face upcoming harsh realities is a delicate balancing act that needs to be further explored. PMID- 17279237 TI - Amyotrophic lateral sclerosis: update for family physicians. AB - OBJECTIVE: To discuss the epidemiology, pathogenesis, diagnosis, expected course, prognosis, and treatment of amyotrophic lateral sclerosis (ALS), a degenerative disorder of the nervous system associated with progressive weakness. QUALITY OF EVIDENCE: PubMed and the Cochrane Database of Systematic Reviews were searched using the MeSH headings "amyotrophic lateral sclerosis," "therapy," "epidemiology," and "etiology." Articles containing the best available evidence were reviewed. Most provided level II and III evidence. There were some level I drug trials. MAIN MESSAGE: Amyotrophic lateral sclerosis is associated with progressive dysarthria, dysphagia, and weakness in the extremities. Diagnosis is based on physical examination, electrophysiology, and excluding other confounding conditions. There is no cure for this devastating disorder. Certain treatments, however, can improve survival and quality of life. CONCLUSION: Because ALS is a complex disease, care of ALS patients is best provided at multidisciplinary clinics that specialize in managing patients with this disorder. PMID- 17279242 TI - Synthesis and characterisation of a mixed-valence Mn13 complex with S6 symmetry by using 2-phenoxybenzoate. AB - The synthesis, structure and magnetic properties of [Mn(13)O(8)(OEt)6(O(2)CC(6)H(4)OPh)12] are reported as the first example of a high nuclearity manganese complex with 2-phenoxybenzoate: the complex possesses S6 symmetry and an S = 11/2 ground state. PMID- 17279243 TI - Solid- and solution-state structures of indium 'alkene analogues'. AB - Although the nuclearity of In(I) 'carbenes' is dependent upon the steric demands of the supporting beta-diketiminate ligand, it is shown by solution NMR diffusion (DOSY) methods that the In-In interactions observed in the solid-state are very weak and not retained in solution. PMID- 17279244 TI - Enantiomeric resolution of supramolecular helicates with different surface topographies. AB - The enantiomeric resolution of an extended range of di-metallo supramolecular triple-helical molecules are reported. The ligands for all complexes are symmetric with two units containing an aryl group linked via an imine bond to a pyridine. Alkyl substituents have been attached in different positions on the ligand backbone. Previous work on the parent compound, whose molecular formula is [Fe(2)(C(25)H(20)N(4))(3)]Cl4, showed that it could be resolved into enantiomerically pure solutions using cellulose and 20 mM aqueous sodium chloride. In this work a range of mobile phases have been investigated to see if the separation and speed of elution could be increased and the amount of NaCl co eluted with the compounds decreased. Methanol, ethanol and acetonitrile were considered, together with aqueous NaCl : organic mixtures. Effective separation was most often achieved when using 90% acetonitrile : 10% 20 mM NaCl (aq) w/v, which gives scope for scaling up to incorporate the use of HPLC. The overall most efficient (i.e. fastest) separation was generally achieved where the cellulose column was packed with 20 mM NaCl (aq) and the column first eluted with 100% acetonitrile, then with 75% ethanol : 25% 20 mM NaCl (aq) until the M enantiomer had fully eluted and finally with 90% acetonitrile : 10% 20 mM NaCl (aq) until the P enantiomer had been collected. The sequence of eluents ensured minimum NaCl accompanying the enantiomers and minimum total solvent being required to elute the enantiomers, especially the second one, from the column. No helicate with a methyl group on the imine bond could be resolved and methyl groups on the pyridine rings also have an adverse effect on resolution. PMID- 17279245 TI - In vitro DNA scission activity of heterometallocenes. AB - A comparative DNA scission activity study of azaferrocene, N-methyl-azaferrocene iodide and 3,3',4,4'-tetramethyl-1,1'-diphosphaferrocene (featuring iron in a +2 oxidation state), along with ferrocene (iron +2) and ferrocenium (iron +3) cation is described. Experiments indicate a high cleavage activity of azaferrocene and its N-methyl derivative in DMSO. DNA cleavage activity can be slowed down by addition of a free radical scavenger (thiourea) or triggered by addition of a reductive agent (dithiothreitol, DTT). The X-ray crystal structure of the N methyl-2,5-dimethylazaferrocene cation (iron +2) with hexafluorophosphate as counter anion is also reported. PMID- 17279246 TI - Syntheses and structures of heterometallic clusters by the reaction of o carboranyl cobaltadichalcogenolato complexes. AB - Metalladichalcogenolate cluster complexes [Cp'Co{E(2)C(2)(B(10)H(10))}]{Co2(CO)5} [Cp' = eta5-C5H5, E = S(3a), E = Se(3b); Cp' = eta5-C5(CH3)5, E = S(4a), E = Se(4b)], {CpCo[E(2)C(2)(B(10)H(10))]}(2)Mo(CO)2] [E = S(5a), Se(5b)], Cp*Co(micro2-CO)Mo(CO)(py)2[E(2)C(2)(B(10)H(10))] [E = S(6a), Se(6b)], Cp*Co[E(2)C(2)(B(10)H(10))]Mo(CO)2[E(2)C(2)(B(10)H(10))] [E = S(7a), Se(7b)], (Cp'Co[E(2)C(2)(B(10)H(10))]W(CO)2 [E(2)C(2)(B(10)H(10))] [Cp' = eta5-C5H5, E = S(8a), E = Se(8b); Cp' = eta5-C5(CH3)5, E = S(9a), E = Se(9b)], {CpCo[E(2)C(2)(B(10)H(10))]}(2)Ni [E = S(10a), Se(10b)] and 3,4-(PhCN(4)S)-3,1,2 [PhCN(4)SCo(Cp)S(2)]-3,1,2-CoC(2)B(9)H(8) 12 were synthesized by the reaction of [Cp'CoE(2)C(2)(B(10)H(10))] [Cp' = eta5-C5H5, E = S(1a), E = Se(1b); Cp' = eta5 C5(CH3)5, E = S(2a), E = Se(2b)] with Co2(CO)8, M(CO)3(py)3 (M = Mo, W), Ni(COD)2, [Rh(COD)Cl]2, and LiSCN4Ph respectively. Their spectrum analyses and crystal structures were investigated. In this series of multinuclear complexes, 3a,b and 4a,b contain a closed Co3 triangular geometry, while in complexes 5a-7b three different structures were obtained, the tungsten-cobalt mixed-metal complexes have only the binuclear structure, and the nickel-cobalt complexes were obtained in the trinuclear form. A novel structure was found in metallacarborane complex 12, with a B-S bond formed at the B(7) site. The molecular structures of 4a, 5a, 6a, 7b, 9a, 9b, 10a and 12 have been determined by X-ray crystallography. PMID- 17279247 TI - Phosphinito- and phosphonito-oxazoline Pd(II) complexes as CO/ethylene insertion intermediates: synthesis and structural characterization. AB - The phosphinito-oxazoline ligand 4,4-dimethyl-2-[methoxy(diphenylphosphine)]-4,5 dihydrooxazole (2a) and the phosphonite-oxazoline ligand 4,4-dimethyl-2 [methoxy(6H-dibenz[c,e][1,2]oxaphosphorin)]-4,5-dihydrooxazole (8a) were prepared by deprotonation of (4,5-dihydro-4,4-dimethyloxazol-2-yl)methanol (1a) and reaction with the corresponding P-Cl function, similar to the ligands 2b (4,4 dimethyl-2-[1-oxy(diphenylphosphine)-1-methylethyl]-4,5-dihydrooxazole) and 8b (4,4-dimethyl-2-[1-oxy(6H-dibenz[c,e][1,2]oxaphosphorin)-1-methylethyl]-4,5 dihydrooxazole) reported previously. These ligands react with [PdClX(COD)] to give complexes of the type [PdClX(P,N)] (3a P,N = 2a, X = Cl; 4a P,N = 2a, X = Me; 4b P,N = 2b , X = Me; 9a P,N = 8a, X = Cl; 9b P,N = 8b, X = Cl; 10a P,N = 8a, X = Me; 10b P,N = 8b, X = Me). Complexes 4a,b and 10a,b reacted with AgCF(3)SO(3) to yield [PdMe(P,N)OSO(2)CF(3)] 5a,b and 11a,b, respectively. From the stepwise insertion reaction of CO and ethylene into the Pd-C bond of 5a and 11a,b, the alkyl ketone chelate complexes [Pd{CH(2)CH(2)C(O)Me}(P,N)]CF(3)SO(3) 7a and 14a,b respectively, have been isolated and spectroscopically characterized. Complexes 3a.CH(2)Cl(2), 5a, 9b, 10a,b, [PdMe(H(2)O)(P,N)]CF(3)SO(3) 12b, (P,N = 8b) and 14a,b have also been characterized by X-ray crystallography and the structures of 14a,b represent still rare examples of structurally characterized CO/ethylene coupling products. PMID- 17279249 TI - Synthesis of alkynylated photo-luminescent Zn(II) and Mg(II) Schiff base complexes. AB - A new series of photo-luminescent Zn(II) and Mg(II) Schiff base complexes were prepared by treatment of the arylethynyl-substituted salicylaldehydes obtained from the Sonogashira reaction with the metal salt followed by addition of the different diamines. Most square-planar Zn(II) complexes exhibited good quantum efficiencies. The Mg(II) complexes displayed even higher quantum yields than the corresponding Zn-complexes. Unsymmetrical Zn(II) Schiff base complexes were also successfully prepared from organic monoimines obtained as intermediates in the formation of the Mg metal Schiff base complex. The monoimine can also be prepared from the reaction of salicylaldehydes with excess diaminoarene. Two crystal structures featuring the zinc atom are reported, one with a rare four-coordinate square planar geometry and the other with a five-coordinate square pyramidal geometry. PMID- 17279248 TI - Insights into the binding properties of a cuprous ion embedded in the tren cap of a calix[6]arene and supramolecular trapping of an intermediate. AB - Coordination of Cu(I) to a tren unit that is covalently linked to a calix[6]arene has been explored. The resulting complex revealed itself very stable in solution under an inert atmosphere, but extremely sensitive to O2 in solution as well as in the solid state. Therefore, its binding properties towards non-redox ligands have been studied in detail. The electron-rich metal center displays moderate affinity for nitrilo ligands compared to the calix[6]tris-pyridine ligand. Indeed, the binding enthalpy with acetonitrile is only -30 kJ mol(-1), whereas it is -72 kJ mol(-1) with the tris-pyridine system. In contrast, CO binding is relatively strong due to important pi-back donation from the metal center, as evidenced by the CO stretch, which was found to be less energetic (2075 cm(-1)) than that measured for ligands based on aromatic donors such as imidazole or pyridine. The conformational and dynamic properties of this calix-system have also been studied in detail. With an empty cavity or with the very small CO guest ligand, the calix-core undergoes partial self-inclusion leading to dissymmetrical conformations. In contrast, nitrilo ligands act as "shoe-trees" that maintain the calix-core in a C(3v) symmetrical cone conformation. Very interestingly, the variable T study relative to the ligand exchange process highlighted a two-step dissociative pathway, where Cu-N bond cleavage/formation is differentiated from the nitrilo guest expulsion/inclusion from/into the calixarene cavity. PMID- 17279250 TI - Dinuclear palladium-azido complexes containing thiophene derivatives: reactivity toward organic isocyanides and isothiocyanates. AB - Cyclopalladated tetranuclear Pd(II) complexes, [Pd2(micro-Cl)2(Y)]2 (Y = L1 or L2; H2L1 = di(2-pyridyl)-2,2'-bithiophene; H2L2 = 5,5''-di(2-pyridyl)-2,2':5',2'' terthiophene), containing two pyridyl-alpha, alpha'-disubstituted derivatives of thiophene were prepared. Treating these products with PR3 and subsequently with NaN3 produced the dinuclear Pd-azido complexes [(PR3)2(N3)Pd-Y-Pd(N3)(PR3)2] (Y = L1 or L2) or a cyclometallated complex [(PR3)(N3)Pd-Y'-Pd(N3)(PR3)] (Y' = C,N L2). Reactions of these Pd-azido complexes with CN-Ar (Ar = 2,6-Me(2)C(6)H(3), 2,6-i-Pr(2)C(6)H(3)) or R-NCS (R = i-Pr, Et, allyl) led to the complexes containing end-on carbodiimido groups [(PMe3)2(N[double bond]C[double bond]N Ar)Pd-Y-Pd(N[double bond]C[double bond]N-Ar)(PMe3)2] or S-coordinated tetrazole thiolato groups {(PMe3)2[CN4(R)]S-Pd-Y-Pd-S[CN4)(R)](PMe3)2}. Interestingly, when treated with elemental sulfur, the carbodiimido complexes transformed into the cyclometallated derivatives, [(PMe3)(N[double bond]C[double bond]N-Ar)Pd-Y' Pd(N[double bond]C[double bond]N-Ar)(PMe3)] (Y' = C,N-L1, C,N-L2). We also report the preparation of linear, thienylene-bridged dinuclear Pd complexes [L2(N3)Pd X(or X')-Pd(N3)L2] (L = PMe3 or PMe2Ph; H2X = 2,2'-bithiophene or H2X' = 2,2':5',2''-terthiophene) and their reactivity toward organic isocyanide and isothiocyanates. PMID- 17279252 TI - Chemistry and biology of resorcylic acid lactones. AB - While resorcylic acid lactones (RALs) have been known for a long time, the more recent discoveries that radicicol is a potent and selective HSP90 inhibitor while other members such as hypothemycin, LL-Z1640-2 and LL-783,277 are potent kinase inhibitors have stimulated a renewed interest in this family of natural products. The recent developments regarding the chemistry and biology of RALs are reviewed. PMID- 17279254 TI - Switching the light emission of (4-biphenylyl)phenyldibenzofulvene by morphological modulation: crystallization-induced emission enhancement. AB - (4-Biphenylyl)phenyldibenzofulvene is weakly luminescent in the amorphous phase but becomes highly emissive upon crystallization; this unusual crystallization induced emission enhancement effect allows its emission to be repeatedly switched between dark and bright states by fuming-heating and heating-cooling processes. PMID- 17279253 TI - Metal cages using a bulky phosphonate as a ligand. AB - The synthesis, structure, magnetic and electronic properties of soluble transition metal phosphonate cages utilizing tritylphosphonic acid (TPA) as ligand are reported. PMID- 17279255 TI - Near IR absorbing planar aromatic [34]octaphyrins(1.1.0.1.1.0.0.0) containing a quaterthiophene subunit. AB - The synthesis and structural characterization of the first examples of planar aromatic core modified [34]octaphyrins(1.1.0.1.1.0.0.0) with three different heteroatoms containing a quaterthiophene subunit are reported. PMID- 17279256 TI - Soft-to-hard transformation of the mechanical properties of dynamic covalent polymers through component incorporation. AB - The mechanical properties of acylhydrazone dynamic polymers may be converted from soft to hard by the incorporation of rigid monomeric components into the original soft polymer backbone, taking advantage of acylhydrazone bond exchange. PMID- 17279257 TI - Design, synthesis and biological evaluation of a macrocyclic discodermolide/dictyostatin hybrid. AB - A 22-membered macrocyclic discodermolide/dictyostatin hybrid has been designed and synthesised; biological evaluation against a range of human cancer cell lines revealed significant levels of growth inhibition. PMID- 17279258 TI - Confinement effects on product selectivity in the pyrolysis of phenethyl phenyl ether in mesoporous silica. AB - Pyrolysis of phenethyl phenyl ether confined in mesoporous silicas by covalent grafting results in significantly increased product selectivity compared with fluid phases. PMID- 17279259 TI - Nanostructural control of cup-stacked carbon nanotubes with 1-benzyl-1,4 dihydronicotinamide dimer via photoinduced electron transfer. AB - The photoinduced electron-transfer reduction of cup-stacked carbon nanotubes (CSCNTs) with 1-benzyl-1,4-dihydronicotinamide dimer [(BNA)2] results in the electrostatic destacking of CSCNTs to afford CSCNTs with uniform size. PMID- 17279260 TI - Structurally characterized intermediates in the stepwise insertion of CO-ethylene or CO-methyl acrylate into the metal-carbon bond of Pd(II) complexes stabilized by (phosphinomethyl)oxazoline ligands. AB - The initial CO-ethylene or CO-methyl acrylate insertion steps into the Pd-Me bond of methylpalladium(II) complexes with (phosphinomethyl)oxazoline ligands, leading to metallacycles, have been fully characterized, including by X-ray diffraction. PMID- 17279261 TI - Rapid ambient mass spectrometric profiling of intact, untreated bacteria using desorption electrospray ionization. AB - Desorption electrospray ionization (DESI) allows the rapid acquisition of highly reproducible mass spectra from intact microorganisms under ambient conditions; application of principal component analysis to the data allows sub-species differentiation. PMID- 17279262 TI - Very large acceleration of the photoinduced electron transfer in a Ru(bpy)3 naphthalene bisimide dyad bridged on the naphthyl core. AB - By linking a naphthalenebisimide (NBI) unit to [Ru(bpy)3]2+ on the naphthyl core the rate of photoinduced Ru-to-NBI electron transfer was 1000-fold increased compared to the case with a conventional linking on the nitrogen. PMID- 17279263 TI - A triptycene-based polymer of intrinsic microposity that displays enhanced surface area and hydrogen adsorption. AB - A novel triptycene-based polymer of intrinsic microporosity (Trip-PIM) displays enhanced surface area (1065 m2 g(-1)) and reversibly adsorbs 1.65% hydrogen by mass at 1 bar/77 K and 2.71% at 10 bar/77 K. PMID- 17279264 TI - Fluorescence enhancements of benzene-cored luminophors by restricted intramolecular rotations: AIE and AIEE effects. AB - Photoluminescence of simple arylbenzenes with ready synthetic accessibility is enhanced by two orders of magnitude through aggregate formation; viscosity and temperature effects indicate that the emission enhancement is due to the restriction of their intramolecular rotations in the solid state. PMID- 17279265 TI - Sensitive detection of protein by an aptamer-based label-free fluorescing molecular switch. AB - We report an aptamer-based method for the sensitive detection of proteins by a label-free fluorescing molecular switch (ethidium bromide), which shows promising potential in making protein assay simple and economical. PMID- 17279266 TI - From crystal engineering to cluster engineering: How to transform cadmium chloride from 2-D to 0-D. AB - The transformation of a 2-D perovskite structure to "expanded" 2-D and finally to a 0-D hexanuclear cadmium chloride cluster by varying the size of substituents on the associated counterions (H vs. methyl vs. ethyl) is described. PMID- 17279267 TI - Dihydroxylation of 2-vinylaziridine: efficient synthesis of D-ribo phytosphingosine. AB - An efficient and highly stereoselective synthesis of D-ribo-(2S,3S,4R) phytosphingosine was accomplished in 62% overall yield starting from commercially available (2S)-hydroxymethylaziridine via osmium-catalyzed asymmetric dihydroxylation as a key step. PMID- 17279268 TI - Iron-sulfur cluster stability. Kinetics and mechanism of ligand-promoted cluster degradation. AB - Reactivity studies of iron-sulfur cluster proteins with chelating ligands model the reactivity of cluster scaffold proteins such as ISU, and suggest a rate law [k(obs) = k2[ligand]n/{[ligand]n + K(D)}] consistent with formation of a pre reaction complex between the Fe-S protein and one chelate ligand. PMID- 17279269 TI - Lewis base induced tuning of the Ge-Ge bond order in a "digermyne". AB - The reaction of the "digermyne" Ar'GeGeAr' (Ar' = C6H3-2,6(C6H3-2,6-Pr(i)2)2; Ge Ge = 2.2850(6) A) with mesityl isocyanide affords the bis adduct [Ar'GeGeAr'(CNMes)2] which results in the conversion of a Ge-Ge multiple bond to a long Ge-Ge single bond (= 2.6626(8) A). PMID- 17279270 TI - Proline organocatalysis as a new tool for the asymmetric synthesis of ulosonic acid precursors. AB - PEP and aldolase mimicry is the key for a direct organocatalytic entry to precursors of ulosonic acids, biomolecules of enormous importance in biology, chemistry and medicine; in the key aldol reaction the dimethylacetal of pyruvic aldehyde is used as phosphoenolpyruvate (PEP) equivalent and the amino acid proline functions as an organocatalyst, imitating the enzyme. PMID- 17279271 TI - Oxidative stress and endothelial dysfunction. AB - This review focuses on the role of vascular oxidative stress in the development and progression of endothelial dysfunction. We discuss different sources of oxidative stress in the vessel wall, oxidative stress and coagulation, the role of oxidative stress and vascular function in arteries and veins, the flow dependent regulation of reactive oxygen species, the putative impact of oxidative stress on atherosclerosis, the interaction of angiotensin II, oxidative stress and endothelial dysfunction, and clinical implications. PMID- 17279273 TI - [Genomic diagnosis of thrombophilia in women: clinical relevance]. AB - The detection of the DNA-sequence of human coagulation factors and inhibitors has introduced the possibility of differentiated mutation analysis in patients with venous thrombosis. Since venous thromboembolism is a multifactorial disease, women are at an increased risk to develop venous thrombosis due to hormonal contraception, during pregnancy and the puerperium. In addition, pregnancy complications like early or late fetal loss, pregnancy-induced hypertensive disorders and very recently recurrent embryo implantation failure have been suspected to be associated with thrombophilia. Therefore, it is of major importance to define inherited thrombophilic disorders, in which genetic diagnosis is of clinical relevance. While most of the genetic defects described so far represent a risk factor for venous thrombosis, only a minority of these defects actually needs DNA analysis to be detected: mutation analysis is clinically relevant, when factor V Leiden mutation is suspected, because relative risks concerning venous thrombosis as well as pregnancy complications clearly differ between homozygote and heterozygote forms of this frequently observed mutation. Similarly detection of the prothrombin mutation G20210A is of clinical relevance, although data for the very rarely observed homozygote variant are not sufficiently available. In contrast, detection of the homozygote variant of the MTHFR-mutation C677T is not useful, since clinical relevance could not be proven in a majority of studies concerning women specific risk situations. Inherited deficiencies of antithrombin, protein C and protein S are rare with high rates of different mutations. Genetic analysis seems only useful in patients with wide intraindividual variations of coagulation inhibitor activities. Genetic analysis concerning the PAI-1 4G/5G polymorphism or the factor XIII Val34Leu polymorphism can not be recommended in women specific risk situations because of insufficient data. PMID- 17279272 TI - [Prevention of diabetes mellitus: the future of German diabetology]. AB - One of the challenges in clinical diabetology today is to develop and implement diabetes prevention management programs for clinical practice. Recent studies have convincingly demonstrated that lifestyle intervention, addressing diet and exercise as well as pharmacologic preventive strategies reduced the risk of progressing from impaired glucose tolerance to diabetes. With respect to the worldwide burden of diabetes these studies offer a compelling evidence-base for the important translation of the research findings into community-based prevention strategies and the development of a National Diabetes Prevention Program. The workgroup "diabetes prevention" from the German Diabetes Association together with the National Action Forum Diabetes and the German Diabetes Foundation developed a concept for a National Program. This comprises a 3-step intervention: in a first step individuals at high risk to develop type 2 diabetes are identified. The second step provides an intensive group intervention to prevent diabetes and in a third step continuous intervention should facilitate motivation maintenance and evaluation. This third step is the crucial step to maintain the effect in changing lifestyle. Recently, a compendium for diabetes prevention was developed as a practical guideline explaining how to implement prevention programs. This guideline also includes the structure of a national prevention program with a prevention manager having a central role in the concept and suggestions for evaluation and quality control. PMID- 17279274 TI - [Secondary prophylaxis of venous thromboembolism]. AB - Making decisions about any modality of secondary prophylaxis in patients with venous thromobembolism (VTE) has to balance the risk of bleeding induced by anticoagulants against the benefit of reducing the risk of recurrent disease. It has to be kept in mind that the magnitude of risk is not only defined by the number of events per time period but also by the impact of the event on the fate of the patient. With standard intensity vitamin K antagonists (VKA), the risk of bleeding is more closely related to comorbidities than to other factors, eg age. The risk of VTE recurrence differs largely between patient groups. The criterion of presence or absence of a permanent or transient clinical trigger factor for the actual VTE episode has a greater impact than an abnormal result in thrombophilia testing. The standard period of secondary prophylaxis for proximal DVT and for PE is three to six months. The concept of prolonging this period for several months according to the risk of recurrence is seriously challanged by the observation that the prolongation period seems to delay recurrencies rather than truly avoiding them. For this reason, patients who clearly are threatened by recurrent episodes should receive indefinitive secondary prophylaxis. This is the case for cancer patients, patients with the antiphospholipid syndrome, and those who belong to families with severe and symptomatic protein C, protein S, or antithrombin deficiencies. Patients with recurrent VTE, with idiopathic VTE, or with combined thrombophilic conditions may only benefit from indefinitive secondary prophylaxis if the bleeding risk of the anticoagulant regimen under consideration is very low. PMID- 17279275 TI - New anticoagulants: from bench to bedside. AB - Heparins and vitamin K antagonists have been the cornerstones of anticoagulation therapy for several decades. Although they are very effective at inhibiting the coagulation process, they have several practical limitations. This was a challenge for the development of therapies that will overcome these drawbacks while matching the efficacy of the two classes of anticoagulants. Advances were achieved in the development of safer, convenient, more specific treatments, which should provide predictable anticoagulant responses and substantially improve the prevention and management of thromboembolic disorders. In the search for new agents matching the ideal anticoagulant profile, different steps in the coagulation cascade have been targeted, including direct thrombin inhibition, and inhibition of factor Xa, factor IXa, the factor Vlla-tissue factor complex and the factor Va-factor Vllla complex. The most advanced clinical development has been achieved with direct factor Xa- and factor IIa-inhibitors which may replace conventional anticoagulants for long-term prevention and treatment of venous and arterial thromboembolic complications. PMID- 17279276 TI - [First results of the THROMKID study: a quality project for the registration of children und adolescents with hereditary platelet function defects in Germany, Austria, and Switzerland]. AB - THROMKID is a quality project of the Paediatric Group of German Thrombosis and Haemostasis Research Society (GTH). Data from paediatric patients with hereditary thrombocytopathies (HT) treated in Germany, Austria, and Switzerland were obtained between May 2005 and August 2006. By evaluation of results of platelet function tests criteria were determined to assess the diagnosis in each patient into most likely, likely or unlikely. A total of 215 patients treated in 31 centers were identified. In 95 patients (44%) the diagnosis of HT was most likely, in 28 (13%) likely and in 92 (43%) unlikely. Taken the first two groups together (n = 123) the diagnoses were as follows: Glanzmann thrombasthenia (n = 39, 32%), Aspirin-like defect (n = 26, 21%), thrombocyte receptor defects (n = 21, 17%), storage pool disorders (n = 18, 15%), Bernard-Soulier syndrome (n = 10, 8%), Hermansky-Pudlak syndrome (n = 6, 5%) and MYH9-related hereditary makrothrombocytopenia (n = 3, 2%). The low prevalence of these diseases and the high percentage of patients with unclassified HT stresses the necessity for the establishment of a competence network for comprehensive care of these patients in the three German-speaking countries. PMID- 17279277 TI - New locations of intravascular tissue factor: indications. AB - Tissue factor (TF) is the major initiator of blood coagulation, and a mediator of inflammation, angiogenesis, and carcinogenesis. According to recent evidence, preformed TF and inducible expression of the protein is observed in several blood components. TF is apparently constitutively expressed on circulating microparticles, and can be exposed within minutes on the cell membrane of activated eosinophils and platelets, and, potentially, on neutrophils. Expression in monocytes and neutrophils largely requires transcriptional activation of the TF gene. Eosinophils appear to harbour the highest concentration of preformed TF among all blood components under resting conditions. TF expression in eosinophil progenitor cells is substantially higher than in precursors of other granulocyte fractions. Eosinophil TF promotes transendothelial migration, which documents that presynthesized TF in blood supports functions apart from coagulation. It is still an open question how the intravascular TF is activated to trigger initiation of coagulation. TF activation in different blood components is likely to be differentially regulated according to the (patho)physiologic context. PMID- 17279278 TI - [Therapeutic options to improve the microcirculation in sepsis and septic shock]. AB - The severe impairment of the microcirculation plays a substantial role in the pathogenesis of severe sepsis and septic shock, and leads to multiple organ failure and death. Therapeutic strategies to resuscitate the microcirculatory blood flow and to improve the functional capillar density are therefore essential to surmount the microcirculatory pathology and to avoid tissue hypoxia. Based on reasonable scientific evidence, early fluid resuscitation directed by defined haemodynamic and metabolic goals (EGDT) as well as the application of activated protein C (rhAPC) according to the guidelines could be recommended. Dobutamine is the first choice to improve cardiac output and to overcome myocardial depression in septic shock whereas phosphodiesterase-III-inhibitors and levosimendane are still experimental options. Furthermore selective inhibitors of iNOS, nitroglycerol, as well as vasopressin have to be investigated relating to their specific effects on the microcirculation and their influence on survival in seevere sepsis and septic shock. PMID- 17279279 TI - [Anti-metastatic effects of serine protease inhibitors: animal models for analysis]. AB - To date, no effective adjuvant drug preventing the aggressive spread of tumour cells in late stages of cancer disease or at the time-point of primary tumour removal is available. Although proteases, including members of the large serine protease family, were shown to be promising targets for an anti-metastatic cancer therapy, synthetic protease inhibitors (SPIs) have so far failed to be introduced into the clinic. In addition to considerations in the design of classical in vivo -tests of SPIs as cancer therapy agents, we here review our findings with a straightforward, highly sensitive and very fast in vivo metastasis model and its implications in the development of efficient anti-metastatic SPIs. The lacZ tagging of tumour cells of this very aggressive T-cell lymphoma model allowed highly sensitive and reproducible detection of metastases within seven days after tumour cell inoculation by X-gal staining of whole organs, allowing cost effective and material-saving side-by-side screening of a series of SPIs with different specificities for different serine proteases. By establishment of specificity/antimetastatic efficacy correlations we identified coagulation factor Xa as one important target of anti-metastatic SPIs and could use this information for the subsequent design and optimization of factor Xa-specific lead structures. CONCLUSION: We exemplify the usefulness of high-throughput in vivo analysis to direct optimization of lead structures and how this may allow unexpected insight into the molecular biology of metastasis. PMID- 17279280 TI - Iron bioavailability as a protective factor against anemia among children aged 12 to 16 months. AB - OBJECTIVE: This study investigates the nutritional factors that determine the absence of anemia in infants from families with a low socioeconomic background submitted to a nutrition intervention program, as well as iron intake according to recommendations. METHODS: The study included 369 children from a cohort of inhabitants of Sao Leopoldo, state of Rio Grande do Sul, Brazil, who were randomized at birth into an intervention group and into a control group. The intervention group had nutritional guidance in the first year of life, with monthly follow-up home visits, whereas the control group was visited at 6 and 12 months, without nutritional intervention. At the end of the first year of life, a 24-hour recall was used. Anemia was diagnosed based on a hemoglobin level less than 11 g/dL. The children's diets were classified according to iron bioavailability. RESULTS: The prevalence of anemia amounted to 63.7% in this study. The proportion of children with adequate iron intake relative to the recommendations was statistically higher in the nonanemic group (26.8%) than in the anemic one (17.7%). Nonanemic children had a greater intake of iron (p = 0.019), vitamin C (p = 0.001), energy density at dinner (p = 0.006), iron density per 1,000 calories (p = 0.045); and 16.3% of them had a diet with high iron bioavailability (p = 0.002). CONCLUSIONS: A diet with high iron bioavailability protects children from anemia and can be used as an intervention measure by basic health services and by the municipal departments of children's education. PMID- 17279281 TI - Effect of evaporation and pasteurization in the biochemical and immunological composition of human milk. AB - OBJECTIVE: To assess the effects of evaporation and pasteurization of human milk on its biochemical and immunological composition and on its osmolarity. METHODS: The samples of mature human milk were categorized into four study groups: in natura human milk, pasteurized human milk, human milk evaporated at 70% of the baseline volume and human milk pasteurized and evaporated at 70%, with 12 different samples of milk in each group. The samples were used to determine the concentrations of sodium, potassium, calcium, phosphorus, magnesium, protein, fat, lactose, immunoglobulin A and osmolarity. RESULTS: The pasteurization of human milk did not show statistically significant changes in the concentration of sodium, potassium, calcium, phosphorus, magnesium, protein, fat, lactose, or in osmolarity; however, it showed remarkable reduction in the mean concentration of immunoglobulin A. Evaporation had a mean increase of 38% in the concentration of sodium, potassium, calcium, phosphorus, magnesium, protein, fat and lactose and mean reduction of 45% in the concentration of immunoglobulin A, without significant change in osmolarity in unprocessed milk. CONCLUSION: By evaporation at 70% of the baseline value of human milk, it is possible to obtain human milk that meets the nutritional requirements recommended for preterm infants, except for calcium and phosphorus. PMID- 17279283 TI - Streptococcus pneumoniae: a study of strains isolated from cerebrospinal fluid. AB - OBJECTIVE: To determine the frequency of capsular serotypes and the antimicrobial susceptibility of strains of Streptococcus pneumoniae, as well as to provide recommendations on the use of available vaccines and antimicrobial drugs. METHODS: In this retrospective study, standard procedures were followed to identify, serotype, and determine bacterial susceptibility to penicillin, cefotaxime, and vancomycin. Pneumococcal strains were isolated from the cerebrospinal fluid (CSF) of patients admitted to nine public and three private hospitals in Distrito Federal, Brazil, between January 1995 and December 2004. Identification and antimicrobial susceptibility tests were carried out at the Central Laboratory of Public Health (Laboratorio Central de Saude Publica). Serotyping was performed at Instituto Adolfo Lutz. RESULTS: A total of 232 pneumococcal strains were isolated, including 126 (54.31%) strains from male patients. Patients had an age range of 0 to 62 years and were distributed into four age groups: 0 to 5, 6 to 17, 18 to 50, and above 50. From the 36 distinct serotypes identified, eight were more prevalent: 14, 6B, 18C, 5, 19F, 23F, 9V, and 6A. The oxacillin test identified 67 penicillin-resistant strains, out of which 47 were confirmed by the E test as having intermediate level of resistance. None of the strains exhibited high-level resistance. CONCLUSION: Pneumococcal resistance to penicillin has gradually increased over the last 10 years in Distrito Federal. Serotypes more frequently isolated in the 0 to 5 years age group were the same involved in penicillin-resistance, all of which are covered by the 7-valent vaccine. PMID- 17279282 TI - Socioeconomic and dietary risk factors for anemia in children aged 6 to 59 months. AB - OBJECTIVE: The objective of this study was to use statistical modeling to identify risk factors for anemia in children aged 6 to 59 months in the state of Pernambuco, covering socioeconomic and dietary aspects. METHODS: The sample comprised 746 children aged between 6 and 59 months from the state of Pernambuco. Their hemoglobin was assayed and a 24-hour dietary recall performed. Risk of anemia was analyzed with relation to socioeconomic variables and to dietary intakes, using multivariate analysis models. RESULTS: The risk factors for anemia were: a high proportion of calories from cow's milk, low density of nonheme iron, low age and low maternal educational level; age was the most prominent factor, with children under 24 months exhibiting 3.61 times greater risk of being anemic than the older children. CONCLUSIONS: This study confirms the need for a clear picture of the dietary intake of children in Brazil, in order that associations with anemia can be better understood. Our results revealed that the dietary factors which were most responsible for risk of anemia were a greater proportion of calories from cow's milk and lower density of nonheme iron, in addition to age below 24 months and low maternal educational level. PMID- 17279284 TI - Langerhans cell histiocytosis: a 16-year experience. AB - OBJECTIVES: To describe the clinical course of Langerhans cell histiocytosis and to compare its outcome according to age, staging of the disease and treatment response. METHODS: Retrospective analysis of data on 33 children with Langerhans cell histiocytosis followed at Hospital das Clinicas, Universidade Federal de Minas Gerais, Brazil, between 1988 and 2004. RESULTS: Age at diagnosis ranged from 2 months to 16 years (median: 2.5 years). Seventeen children were male. The follow-up period varied from 21 days to 16.2 years (median: 3.4 years). The most common clinical manifestations at diagnosis were osteolytic lesions, enlarged lymph nodes and skin lesions. The overall survival rate for the whole group was 86.1% at 16 years (95%CI 66.6-94.6%). Deaths occurred in patients with multisystem disease and organ dysfunction at diagnosis. Those patients who had a "better" response to treatment in the sixth week were likely to have a significantly higher overall survival rate than those who showed disease progression. Overall survival rate was significantly higher for patients with single-system disease. The disease-free survival rate for the whole group was 30.9% at 16 years (95%CI 15.6-47.5%), and was significantly higher for those with single-system disease. Age groups were not associated with different disease-free survival rates. Diabetes insipidus was the most common sequela. No cases of secondary neoplasms were observed. CONCLUSION: The clinical manifestations of Langerhans cell histiocytosis vary widely, with a high relapse rate and low mortality rate. PMID- 17279285 TI - Factors associated with risk of low dietary fiber intake in adolescents. AB - OBJECTIVE: To evaluate dietary fiber intake among adolescents and to analyze factors associated with the risk of insufficient consumption of this nutrient. METHODS: Cross-sectional study of 722 adolescents from the town of Sao Leopoldo, RS, Brazil. Sampling was by clusters, with a systematic randomization of 40 census sectors and residences, including all individuals aged 10 to 19 years. The adolescents' weight and height were measured and sociodemographic data on their families recorded. A 24-hour dietary recall and a frequency survey were used to assess dietary intakes. The quantity of dietary fiber in diets was calculated using Nutwin nutrition support software (Programa de Apoio a Nutricao), developed by the IT Department at Universidade Federal de Sao Paulo (UNIFESP). Statistical analysis was by means of logistic regression, employing a hierarchical model. RESULTS: The prevalence of insufficient dietary fiber intake was 69% among girls and 49.7% for boys (p < 0.001). The determinant factors of this condition among boys were non-habitual consumption of beans (OR 2.65; 95%CI 1.05-6.68) and excessive fat intake (OR 2.67; 95%CI 11.23-5.83). For girls factors were increased age (OR 5.33; 95%CI 2.33-12.2), non-habitual consumption of beans (OR 3.01; 95%CI 1.44-6.53), excessive fat intake (OR 1.85; 95%CI 1.01-3.37), dieting for weight loss (OR 2.50; 95%CI 1.10-5.70) and presence of overweight (OR 2.06; 95%CI 1.04-4.07). CONCLUSIONS: These results admit of the conclusion that excessive fat consumption and non-habitual consumption of beans are strongly linked with the risk of insufficient dietary fiber intake in both sexes and that females exhibit a greater number of risk factors for this outcome. PMID- 17279286 TI - Percutaneous subclavian central venous catheterization in children and adolescents: success, complications and related factors. AB - OBJECTIVE: The objective of this study was to investigate the rates of success and of complications of percutaneous subclavian central venous catheterization in children and adolescents and to identify factors associated with them. METHODS: This was a study of a series of 204 percutaneous subclavian central venous catheterizations of children and adolescents, using polyvinyl chloride catheters (Intracath(R)), at the Instituto Materno-Infantil Professor Fernando Figueira between December 1, 2003 and April 30, 2004. An analysis was performed of variables related to the patient, such as age, and of variables related to the procedure, such as success/failure, type of anesthesia, complications, who performed the procedure and the number of attempts needed. RESULTS: Overall, 89.2% of catheterizations were successful. Percentage success rates were significantly greater when percutaneous subclavian central venous catheterization was performed with the child sedated (94%). Around 43.2% of subclavian catheterizations progressed with complications related to insertion of the catheter; however, complications of greater severity were observed in just 3.5% of cases. There were a greater number of complications related to percutaneous subclavian central venous catheterizations performed by a first-year resident (58.8%), who performed a significantly greater percentage of procedures on children younger than 1 year and who also made a greater number of attempts per patient. CONCLUSIONS: The chance of success was greater when patients were sedated for catheterization. There was a greater chance of complications related to insertion of the catheter when percutaneous subclavian central venous catheterization was performed by less experienced physicians, and it would be prudent to designate those central venous catheterizations that present greater risk to surgeons with greater experience. PMID- 17279287 TI - Metabolic syndrome: definition and prevalence in children. PMID- 17279288 TI - Obesity, insulin resistance and the metabolic syndrome. PMID- 17279289 TI - The quality of care of very low birth weight babies in Brazil. PMID- 17279291 TI - Feeding habits of children aged 6 to 12 months and associated maternal factors. AB - OBJECTIVE: To identify the feeding practices of children aged 6 to 12 months of age and associated maternal factors. METHODS: This was a cross-sectional study analyzing data from the 2004 Breastfeeding and the Municipalities Project, which was implemented in 136 municipalities in the state of Sao Paulo, Brazil, with 24,448 children. The foods these children ate were profiled according to the number of children who had been given breastmilk and/or other foods during the previous 24 hours, and based on this data the probability of consumption of each food at each age was estimated by means of probit analysis. RESULTS: It was observed that 50% of the sample were being given breastmilk, 77% other types of milk, 63% porridge, 87% fruit, 78% soups, 64% the family meal, 58% meals including beans and 36% soup or meals containing meat. The probability of a 6 month-old child being given soup is elevated (78%), while for the family meal it is low (39%), and the probability of being fed breastmilk is 59%, lower than for other milks (70%) and than for porridge (63%). Associations were observed between milk-based meals and primiparous mothers, mothers employed outside the home and mothers who had spent longer in education. Similar findings were observed for soups, added to maternal age of more than 20 years. The family meal was associated with mothers under 20 years old, mothers who were not employed outside the home, mothers with fewer years' education and multiparous mothers. CONCLUSIONS: Excessive consumption was observed of liquid and semi-solid foods, suggesting that appropriate guidance on complementary feeding is needed, taking into account age, primiparity, education and employed mothers. PMID- 17279290 TI - Food allergy: a practical update from the gastroenterological viewpoint. AB - OBJECTIVE: To present an up-to-date and critical review regarding food allergies, focusing mainly on treatment and prevention. SOURCES: Review of published literature searched on MEDLINE database; those data which were the most up-to date and representative were selected (2000-2006). The search included the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the American Academy of Pediatrics (AAP). SUMMARY OF THE FINDINGS: The prevalence of allergic diseases has increased over the last decades, and food allergy seems to be part of this increase. Food allergy is much more common in pediatrics and has a significant medical, financial and social impact on young children and their families. Treatment and prevention of food allergy is a major challenge for public health, scientific and medical communities. There is a lot of misinformation and the medical management of this condition is still discussable. We present and discuss the guidelines regarding criteria for the prevention of food allergy and atopic diseases published by the Nutrition Committees of ESPGHAN jointly with the European Society for Pediatric Allergy and Clinical Immunology (ESPACI) and AAP. CONCLUSION: The overdiagnosis of food allergy is quite prevalent. There is a need for standardization of definitions and diagnostic procedures. The primary goal of therapy should be to first establish effective means of preventing food allergies. There is a need for accurate diagnostic methods to confirm or rule out the diagnosis. Patients need appropriate treatment by eliminating foods that cause symptoms, while avoiding the nutritional side effects and the cost of inappropriate diets. PMID- 17279292 TI - The correlation between aerobic mesophilic microorganism counts and Dornic acidity in expressed human breastmilk. AB - OBJECTIVE: The study was designed to test for the existence of a correlation between the total population of aerobic mesophilic microorganisms in processed raw breastmilk from a human milk bank and the Dornic acidity of that milk. METHODS: Two hundred consecutive samples of thawed expressed human breastmilk obtained from human milk bank, prior to pasteurization. Dornic acidity was titrated in triplicate for each sample. Aerobic mesophilic microorganisms were then plate counted. Data were analyzed to detect correlations between variables, using Pearson's coefficient, and the level of significance was set at p < or = 0.05. RESULTS: In the samples analyzed, Dornic acidity levels had a positive (R = 0.948) and statistically significant (p < or = 0.001) correlation with the population of aerobic mesophilic microorganisms (CFU/mL). CONCLUSIONS: The data obtained here support to the conclusion that Dornic titration is an effective method for the indirect evaluation of bacterial growth in expressed human milk. PMID- 17279293 TI - Total IgE in respiratory allergies and infections by intestinal parasites. PMID- 17279296 TI - Exacerbation of infectious diseases by iron supplementation. PMID- 17279297 TI - Severe complications with diclofenac after colonic resection. PMID- 17279298 TI - Muscle interposition in patients with fistulas between the rectum and urethra or vagina. PMID- 17279299 TI - Unilateral pudendal neuropathy is common in patients with fecal incontinence. AB - PURPOSE: Pudendal neuropathy and fecal incontinence frequently coexist; however, the contribution of neuropathy is unknown. The pudendal nerve innervates the external anal sphincter muscle, anal canal skin, and coordinates reflex pathways. Lateral dominance or a dominantly innervating nerve and its subsequent damage may have major implications in the etiology and treatment of fecal incontinence. This study was designed to establish the prevalence of pudendal neuropathy, in particular a unilateral one, and to examine the impact on anorectal function. METHODS: A total of 923 patients (745 females; mean age, 52 (range, 17-92) years) with fecal incontinence were studied using endoanal ultrasonography, anorectal manometry, rectal sensation, and pudendal nerve terminal motor latencies. RESULTS: A total of 520 patients (56 percent) demonstrated a pudendal neuropathy, which was unilateral in 38 percent (351 patients; 169 right-sided, 182 left sided). Neuropathy, whether it was bilateral (bilateral vs. normal; 56 (range, 7 154) cm H2O) vs. 67 (range, 5-215) cm H2O; P < 0.01) or unilateral (unilateral vs. normal; 61 (range, 0-271) cm H2O vs. 67 (range, 5-215) cm H2O; P = 0.04) was associated with reduced anal resting tone. This also was seen with respect to squeeze increments (bilateral vs. normal; 34 (range, 0-207) cm H2O vs. 52 (range, 0-378) cm H2O; P < 0.001, unilateral vs. normal; 41 (range, 0-214) cm H2O vs. 52 (range, 0-378) cm H2O; P < 0.01). In those with intact sphincters, unilateral neuropathy was associated with reduced squeeze increments (unilateral vs. normal; 60 (range, 10-286) cm H2O vs. 69 (range, 7-323) cm H2O; P = 0.01) but no significant reduction in resting pressures. There was no association between pudendal neuropathy and abnormal rectal sensitivity. CONCLUSIONS: Unilateral pudendal neuropathy is a common abnormality in individuals with fecal incontinence and is significantly associated with both attenuated resting pressures and squeeze increments. Although there are limitations in the interpretation of pudendal nerve terminal motor latencies, this study demonstrates that further exploration of the concept of lateral dominance is needed. PMID- 17279300 TI - Combined ciprofloxacin and tinidazole therapy in the treatment of chronic refractory pouchitis. AB - PURPOSE: Management of chronic refractory pouchitis, a common cause for pouch failure with pouch resection or diversion, is often challenging. The aim of this study was to assess the efficacy and safety of a combination therapy of ciprofloxacin and tinidazole in patients with chronic refractory pouchitis compared with mesalamine therapy. METHODS: Sixteen consecutive ulcerative colitis patients with chronic refractory pouchitis (disease>4 weeks and failure to respond to>4 weeks of single-antibiotic therapy) were treated with a four-week course of ciprofloxacin 1 g/day and tinidazole 15 mg/kg/day. A historic cohort of ten consecutive patients with chronic refractory pouchitis treated with oral (4 g/day), enema (8 g/day), or suppository (1 g/day) mesalamine served as controls. The Pouchitis Disease Activity Index, clinical remission, clinical response, the Cleveland Global Quality of Life, the Irritable Bowel Syndrome-Quality of Life, and the Short Inflammatory Bowel Disease Questionnaires scores were calculated before and after therapy and compared between the two treatment groups. RESULTS: Patients taking ciprofloxacin and tinidazole had a significant reduction in the total Pouchitis Disease Activity Index scores and subscores and a significant improvement in quality-of-life scores (P < 0.002). For patients in the mesalamine group, there was a significant reduction in the total Pouchitis Disease Activity Index scores only. Patients in the antibiotic group had a greater reduction in the total Pouchitis Disease Activity Index scores and a greater improvement in the quality-of-life scores than those in the mesalamine group (P 10 cm, 194 with bilateral deposits, 140 with four or more liver metastases, and 73 with extrahepatic disease. The overall actuarial survival rates at one, three, five, and ten years were 88, 67, 45, and 36 percent, respectively, for patients with classic indications and 84, 53, 34, and 24 percent, respectively, for patients with expanded indications (P = 0.0009). In the group of expanded indications, there were more patients who received preoperative than postoperative chemotherapy: 72 (28 percent) vs. 18 (7 percent; P < 0.0001), and 148 (70 percent) vs. 131 (61 percent; P = 0.0466). In a multivariate analysis, four or more liver metastases and extrahepatic disease were independent predictors of poor outcome. Adjuvant chemotherapy significantly improved survival (P = 0.0002). CONCLUSIONS: This study suggested that liver resection should be indicated in patients with expanded indications. The extent of the benefits of preoperative and postoperative chemotherapy needs to be quantitated. PMID- 17279303 TI - The role of endoscopic extraperitoneal herniorrhaphy: where do we stand in 2005? AB - Inguinal hernia repair is a common surgical procedure, but the most effective surgical technique remains controversial. The evolution of laparoscopic techniques has allowed reproduction of open preperitoneal repair via an endoscopic total extraperitoneal (TEP) approach. More recently, the advent of comprehensive training in laparoscopy has allowed TEP to continue evolving as the feasibility of this approach gains recognition as a preferable technique. Once considered very difficult to learn, TEP currently is adequately taught in many surgical training programs. This report reviews the fundamentals and details various modifications that make this procedure more desirable than open procedures and other laparoscopic techniques. A resultant decrease in operative time, cost of the procedure, and morbidity to the patient is routine. In addition, the authors review their institutional experience and examine other current evidence-based data. PMID- 17279304 TI - Remote telepresence surgery: the Canadian experience. AB - On 28 February 2003, the world's first telerobotic surgical service was established between St. Joseph's Healthcare Hamilton, a teaching hospital affiliated with McMaster University, and North Bay General Hospital, a community hospital 400 km away. The service was designed to provide telerobotic surgery and assistance by expert surgeons to local surgeons in North Bay, and to improve the range and quality of advanced laparoscopic surgeries offered locally. The two surgeons have collaboratively performed 22 remote telepresence surgeries including laparoscopic fundoplications, laparoscopic colon resections, and laparoscopic inguinal hernia repairs. This article describes the important lessons learned, including the telecommunication requirements, the impact from lack of haptic feedback, surgeons' adaptation to latency, and ethical and medicolegal issues. This is currently the largest clinical experience with assisted robotic telepresence surgery (ARTS) in the world, and the lessons learned will help guide the future design and development of telesurgical robotic platforms. It also will guide the establishment of telesurgical networks connecting various centers in the world, allowing for rapid and safe dissemination of new surgical techniques. PMID- 17279305 TI - The mechanical master-slave manipulator: an instrument improving the performance in standardized tasks for endoscopic surgery. AB - BACKGROUND: This study aimed to evaluate the feasibility and efficacy of a mechanical minimally invasive manipulator for endoscopic surgery. In contrast to currently available motorized master-slave manipulators, this mechanical manipulator consists of two purely mechanical, hand-controlled endoscopic arms with joints that allow seven degrees of freedom (DOF). METHODS: For the study, 30 medical students performed four different tasks in a pelvic trainer box using either two conventional endoscopic needleholders or a set of mechanical manipulators. The exercise consisted of four different tasks: repositioning of coins, rope passing, passing of a suture through rings, and tying of a surgical knot. All experiments were recorded on videotape (S-VHS), and the data were analyzed afterwards by an independent observer using a quantitative time-action analysis. RESULTS: A significant difference in the number of total actions (including failures) favoring the mechanical manipulator group was shown in most exercises. A significant difference in failures per task was shown in favor of the mechanical manipulator group as well. There was no significant difference shown in the total time per exercise. CONCLUSIONS: The tasks clearly demonstrated the efficacy of the mechanical manipulator, although some technical flaws emerged during the experiments. Considering the fact that a first prototype of the mechanical manipulator was tested, modifications are to be expected in a next model. These experiments show the potential of the mechanical manipulator, and it is expected to be a competitive and economical instrument for endoscopic surgery in the near future. PMID- 17279306 TI - Intraoperative localization of early-stage upper gastrointestinal tumors using a magnetic marking clip-detecting system. AB - BACKGROUND: Intraoperative tumor localization often is difficult during laparoscopic surgery for early-stage upper gastrointestinal tumors. METHOD: This study enrolled 15 patients undergoing laparoscopic gastrectomy. A magnetic marking clip-detecting system was used to apply a marking clip to the tumor site during preoperative gastroscopy, and to detect a marking magnetic body. RESULTS: In a basic ex vivo study, the mean permeance rate on the gastric wall serosal surface was 0.97 +/- 0.01. Magnetic flux densities required for exploration were 52.6 mT on the gastric wall serosal surface and 312.4 mT 10 mm away from the surface. In a clinical study, the mean distance between the detected tumor site and the clip along the longitudinal axis was 8.3 +/- 3.2 mm. The mean detection time was 5.7 +/- 2.3 min. CONCLUSION: The magnetic marking clip-detecting system may be useful for tumor site detection during laparoscopic gastrectomy. PMID- 17279307 TI - A prospective randomized comparison of two instruments for dissection and vessel sealing in laparoscopic colorectal surgery. AB - BACKGROUND: A newly available, laparoscopic 5-mm bipolar vessel sealing device promises substantial advantages over the 10-mm instrument. This study compared the safety as well as the technical and surgical aspects of these different tools. METHODS: For this study, 30 consecutive patients undergoing laparoscopic left-sided colectomy were prospectively randomized for the 5-mm LigaSure or The 10-mm LigaSure. The patients' demographics were analyzed together with their intraoperative and postoperative parameters, and the instruments were assessed by the surgeons with a standardized questionnaire. RESULTS: The two groups were comparable and demonstrated similar mean operation times, blood losses, and hospital stays. The 5-mm LigaSure was applied in more operation steps and resulted in fewer bleeding episodes and less lens cleaning. Monopolar scissors were used less frequently in the 5-mm group, thus minimizing cauteric lesions and their complications (0 in the 5-mm group vs 2 in the 10-mm group). Overall satisfaction with the 5-mm LigaSure was significantly higher (8.4 +/- 0.18 vs 6.9 +/- 0.41 out of 10; p = 0.002), with significant advantages in terms of dissection capacity, visibility, and handling. CONCLUSION: The 5-mm LigaSure is as secure and fast as the larger 10-mm device and compares favorably in terms of finer dissection as well as trocar flexibility and handling. Therefore, it can be used safely in laparoscopic colorectal surgery. PMID- 17279308 TI - Further modification of technique for laparoscopic placement of drain following cholecystectomy. PMID- 17279309 TI - Somatostatin analogues, a series of tissue transglutaminase inducers, as a new tool for therapy of mesenchimal tumors of the gastrointestinal tract. AB - Imatinib, a tyrosine kinase inhibitor directed against the enzymatic domain of KIT protein, was found to produce dramatic clinical responses in metastatic gastrointestinal stromal tumors (GISTs). However, resistance usually develops thus determining treatment failure. The present study was performed to analyse the expression of somatostatin receptor (SSTR) subtypes, modulators of tissue transglutaminase, in a series of GISTs and leiomyosarcomas by immunohistochemistry to identify a new potential therapeutic target. Sixteen cases (8 males and 8 females, age range: 38-73; 11 GISTs, 4 leiomyosarcomas, 1 leiomyoma) were studied. Immunohistochemical detection of the relevant SSTRs was performed on paraffin-embedded tissue sections, stained with polyclonal antibodies directed against the five somatostatin receptor subtypes. We found 7 out of 16 (44%) tumors expressing all SSTRs and 14 out of 16 (87%) tumors positive for at least 3 subtypes. SSTR2A was the most represented subtype in the tumors studied, being expressed in approximately 70% of cases exhibiting an intense labeling in most of these cases. The significant expression of SSTRs shown in this series of GISTs and gastrointestinal leiomyosarcomas suggests a potential therapeutic target to be explored alone and/or in combination with other therapeutic agents in the setting of refractory GI stromal tumors. PMID- 17279310 TI - Interobserver variability in confocal optic nerve analysis (HRT). AB - BACKGROUND/AIMS: To study the observer-related variability of optic nerve head (ONH) measurements using confocal laser scanning tomography (HRT I) in a screening setting. METHODS: Six experienced glaucoma specialists independently evaluated 50 ONH topographies from 25 adults using HRT software ver. 2.01 in a masked fashion. ONH topographies were obtained from a cohort study of 882 healthy adults and additionally included one patient with glaucomatous eyes. A glaucoma screening-like setting was intended. The mean interobserver difference was defined as the mean percentual difference between an observer's analysis and the mean of all six observers for all eyes and all observers. The interobserver range was calculated for each eye as the percentual difference between the lowest and highest measurement, with the highest measurement as denominator. Additionally, Kendall's coefficient of rank concordance was assessed for the main HRT parameters. RESULTS: Mean disc area ranged from 1.83 +/- 0.49 to 2.21 +/- 0.40 mm(2) (mean interobserver difference: 8.3%; interobserver range: 5-50%; rank concordance: 0.86). The lowest mean interobserver differences were found for mean retinal nerve fibre layer thickness (RNFLT; 6.5%), maximum cup depth (2.9%) and cup shape (6.8%). An increased interobserver range was significantly correlated to a low cup to disc area ratio (r=0.64, P<0.0001). CONCLUSIONS: The observer dependent diagnostic variability of HRT measurements can lead to divergent diagnostic evaluation of the ONH in a screening setting. Any HRT software relying on a reference database is exposed to relevant observer-related variability of the disc area. For screening purposes, HRT measurements should be completed by other diagnostic methods to compensate for possible diagnostic uncertainty. PMID- 17279312 TI - The large eyes of Wolfgang Amadeus Mozart. (On the occasion of the 250th Mozart anniversary year). AB - This article discusses the eyes of Wolfgang Amadeus Mozart (1756-1791) which, based on portraits, can be said to have a certain noticeable feature--some degree of exophthalmos. In fact, even contemporary observers made particular mention of Mozart's eyes being large. Although cicatricial ectropion, caused by infectious disease, cannot be excluded, mild myopia, in combination with shallow orbits or combined with a genetic predilection, would be one possible explanation for Mozart's large eyes. Graves' orbitopathy, the ophthalmic manifestation of hyperthyroidism, or hypothyroidism have both been suggested to be the cause of Mozart's large eyes. However, these diseases are unlikely causes given their topical and systemic features. PMID- 17279313 TI - Cellular internalization of proinsulin C-peptide. AB - Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide, we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport into nuclei was found using the labeled peptide. The internalization was followed at 37 degrees C for up to 1 h, and was reduced at 4 degrees C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin sensitive mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated binding of HEK 293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action. PMID- 17279314 TI - Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism. AB - The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2 (ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined K(m) values ranged from 0.05 to 0.3 microM and k(cat) values from 2.3 to 17.6 min(-1), while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup. This mutation increased the retinoid activity up to 100-fold. The K(m) values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic retinol oxidation at physiological concentrations. PMID- 17279315 TI - Effects of ulapualide A and synthetic macrolide analogues on actin dynamics and gene regulation. AB - Several marine macrolide toxins act as potent and specific actin-severing molecules. Recent elucidation of their stereochemistries and modes of interaction with actin has allowed the syntheses of bioactive analogues. Here we used synthetic analogues in a structure-function analysis of ulapualide A, a trisoxazole-based macrolide. Ulapualide A harboured potent actin-depolymerising activity both in cells and in vitro. Its synthetic diastereoisomer was three orders of magnitude less active than the natural toxin and synthetic macrolide fragments lacked actin-capping/ severing activity altogether. Modulation of serum response factor (SRF)-dependent gene expression, as described for other actin binding toxins, was also examined. Specific changes in response to ulapualide A were not observed, primarily due to its profound effects on cytoskeletal integrity and cell adhesion. Several synthetic fragments of ulapualide A also had no effect on SRF-dependent gene expression. However, inhibition was observed with a molecule corresponding to the extended aliphatic side chain of halichondramide, a structurally related macrolide. These findings indicate that side-chain derivatives of trisoxazole-based macrolides may serve to uncouple gene-regulatory events from actin dynamics. PMID- 17279316 TI - Sulfatide-tenascin interaction mediates binding to the extracellular matrix and endocytic uptake of liposomes in glioma cells. AB - Tenascin-C is an extracellular matrix glycoprotein, whose expression is highly restricted in normal adult tissues, but markedly up-regulated in a range of tumors, and therefore serves as a potential receptor for targeted anticancer drug or gene delivery. We describe here a liposomal carrier system in which the targeting ligand is sulfatide. Experiments with tenascin-C-expressing glioma cells demonstrated that binding of liposomes to the extracellular matrix relied essentially on the sulfatide-tenascin-C interaction. Following binding to the extracellular matrix, the sulfatide-containing liposomes were internalized via both caveolae/lipid raft- and clathrin-dependent pathways, which would ensure direct cytoplasmic release of the cargoes carried in the liposomes. Such natural lipid-guided intracellular delivery targeting at the extracellular matrix glycoproteins of tumor cells thus opens a new direction for development of more effective anticancer chemotherapeutics in future. PMID- 17279317 TI - Chronic sequelae of common elective groin hernia repair. AB - BACKGROUND: The aim of this study was to assess long-term chronic pain, numbness and functional impairment after open and laparoscopic groin hernia repair in a teaching hospital. METHODS: We performed a cross-sectional study in which all adult patients with a groin hernia repair between January 2000 and August 2005 received a questionnaire by post. It contained questions concerning frequency and intensity of pain, presence of bulge, numbness, and functional impairment. RESULTS: One thousand seven hundred and sixty-six questionnaires were returned (81.6%) and after a median follow-up period of nearly 3 years 40.2% of patients reported some degree of pain. Thirty-three patients (1.9%) experienced severe pain. Almost one-fourth reported numbness which correlated significantly with pain (P < 0.001). Other variables, identified as risk factors for the development of pain were age (P < 0.001) and recurrent hernia repair (P = 0.003). One-fifth of the patients felt functionally impaired in their work or leisure activities. CONCLUSION: Chronic pain and functional impairment are very common long-term complications after groin herniorrhapy in Dutch teaching hospitals. PMID- 17279318 TI - Indirect inguinal hernia of the urinary bladder through a persistent canal of Nuck: case report. AB - We report a 79-year-old female cadaver found to harbor an indirect inguinal hernia involving the urinary bladder. Further investigation revealed a patent canal of Nuck. The authors describe this rare finding in an adult and review the pertinent literature regarding such herniation. We believe this to be the first report of an indirect inguinal hernia involving the urinary bladder in a cadaver. This also seems to be the first description of such a hernia via a patent canal of Nuck in an adult. PMID- 17279319 TI - Use of porcine dermal collagen as a prosthetic mesh in a contaminated field for ventral hernia repair: a case report. AB - Chronic infection of a prosthetic mesh implant is a severe complication of ventral hernia repair, and mesh explantation is usually required in these cases. Biologic mesh implants have a possible role in ventral hernia repair in this setting. Here we present a case of chronic mesh infection following ventral hernia repair and the use of a biologic mesh to repair the existing defect following explantation of the infected mesh. Analysis of the explant material demonstrated possible oxidative degradation of the original polypropylene. A review of the literature follows. PMID- 17279321 TI - Comments about "Atherosclerosis in the vertebral artery: an intrinsic risk factor in the use of spinal manipulation? (2006) Surg Radiol Anat 28:129-134, by Cagnie B, Barbaix E, Vinck E, D'Herde K, Cambier D". PMID- 17279323 TI - Accuracy of birth certificate and hospital discharge data: a certified nurse midwife and physician comparison. AB - OBJECTIVES: Birth certificate and hospital discharge data are relied upon heavily for national surveillance and research on maternal health. Despite the great importance of these data sources, the recording accuracy in these datasets, comparing birth attendant type, has not been evaluated. The study objective was to assess the variation in chart documentation accuracy between certified nurse midwives (CNMs) and physicians (MDs) for selected maternal variables using birth certificate and hospital discharge data. METHODS: Data was obtained on women delivering in 10 Washington State hospitals that had both CNM and MD-attended births in 2000 (n = 2699). Using the hospital medical record as the gold standard of accuracy, the true positive rate (TPR) for selected maternal medical conditions, pregnancy complications, and intrapartum and postpartum events was calculated for CNMs and MDs using birth certificate data, hospital discharge data, and both data sources combined. RESULTS: The magnitude of TPRs for most recorded maternal medical conditions, pregnancy complications, and intrapatum and postpartum events was higher for CNMs than for MDs. TPRs were significantly higher in birth certificate records for pregnancy-induced hypertension, premature rupture of membranes, labor augmentation, induction of labor, and vaginal birth after cesarean (VBAC) for CNM-attended births relative to MDs. Among combined data sources, CNM TPRs were significantly higher for pregnancy-induced hypertension and premature rupture of membranes. CONCLUSIONS: CNMs had consistently higher accuracy of recorded maternal medical conditions, pregnancy complications, and intrapartum and postpartum events when compared to MDs for all data sources, with several being statistically significant. Our findings highlight discrepancies between CNM and MD hospital chart documentation, and suggest that epidemiologic researchers consider the issue of measurement error and birth attendant type. PMID- 17279322 TI - The significance of platelet activation in rheumatoid arthritis. AB - We evaluated the significance of platelet activation in patients with rheumatoid arthritis (RA). The expression of CD62P and CD63 by platelets was determined using flow cytometry in 18 active RA patients, 10 remission RA and 15 normal controls. Meanwhile, the erythrocyte sedimentation rate (ESR) and C-reactive protein was also determined in all groups. The expression of CD62P in active RA patients (11.88 +/- 2.47%) was significantly higher than that in remission RA group (2.85 +/- 1.60%; P < 0.01) and control group (2.78 +/- 1.04%; P < 0.01). The expression of CD63 in active RA patients (9.90 +/- 3.02%) was significantly higher than that in remission RA group (4.11 +/- 2.00%; P < 0.01) and control group (4.13 +/- 1.85%; P < 0.01). The level of CRP (54.33 +/- 23.35 mg/l) and ESR (86.06 +/- 33.67 mm/h) in active RA patients was higher than that in remission RA group (2.55 +/- 1.01 mg/l, 14.70 +/- 4.57 mm/h; P < 0.01 for both) and normal control group (3.21 +/- 2.18 mg/l, 12.25 +/- 5.05 mm/h; P < 0.01 for both). There was a positive correlation between CD62P and ESR (r = 0.5224, P < 0.01) and also a positive correlation between CD62P and CRP (r = 0.7048, P < 0.01) as well as between CD63 and ESR (r = 0.4476, P < 0.05) but no correlation between CD63 and CRP. Platelet activation may be a sign of RA exacerbation. PMID- 17279324 TI - The effect of time in the U.S. on the duration of breastfeeding in women of Mexican descent. AB - OBJECTIVES: Although women of Mexican decent have high rates of breastfeeding, these rates may vary considerably by acculturation level. This study investigated whether increased years of residence in the U.S. is associated with poorer breastfeeding practices, including shorter duration of any and exclusive breastfeeding, in a population of low-income mothers of Mexican descent. METHODS: Pregnant women (n = 490) were recruited from prenatal clinics serving a predominantly Mexican-origin population in an agricultural region of California. Women were interviewed during pregnancy, shortly postpartum, and when their child was 6 months, 1 year, 2 years, and 3.5 years of age. RESULTS: Increased years of residence in the U.S. was associated with decreased likelihood of initiating breastfeeding and shorter duration of exclusive and any breastfeeding. Median duration of exclusive breastfeeding was 2 months for women living in the U.S. for 5 years or less, 1 month for women living in the U.S. for 6 to 10 years, and less than one week for women living in the U.S. for 11 years or more, or for their entire lives (lifetime residents). After controlling for maternal age, education, marital status and work status, lifetime residents of the U.S. were 2.4 times more likely to stop breastfeeding, and 1.5 times more likely to stop exclusive breastfeeding, than immigrants who had lived in the U.S. for 5 years or less. CONCLUSIONS: Efforts are needed to encourage and support Mexican-origin women to maintain their cultural tradition of breastfeeding as they become more acculturated in the U.S. PMID- 17279325 TI - Release of intracellular Zn(2+) in cultured neurons after brief exposure to low concentrations of exogenous nitric oxide. AB - Several studies have shown intracellular Zn(2+) release and concomitant cell death after prolonged exposure to exogenous NO. In the present study, we investigated whether cortical neurons briefly exposured to exogenous NO would demonstrate similar levels of intracellular Zn(2+) release and subsequent cell death. Cortical neurons were loaded with the Zn(2+) selective fluorophore FluoZin 3 and treated with various concentrations of the NO generator, spermine NONOate. Fluorescence microscopy was used to detect and quantify intracellular Zn(2+) levels. Concomitant EDTA perfusion was used to eliminate potential effects of extracellular Zn(2+). Neurons were perfused with the heavy metal chelator TPEN to selectively eliminate Zn(2+) induced fluorescence changes. A significant increase of intracellular fluorescence was detected during a 5 min perfusion with spermine NONOate. The increase in intracellular Zn(2+) release appeared to peak at 1 microM spermine NONOate (123.8 +/- 28.5%, increase above control n = 20, P < 0.001). Further increases in spermine NONOate levels as high as 1 mM failed to further increase detectable intracellular Zn(2+) levels. The NO scavenger hemoglobin blocked the effects of spermine NONOate and the inactive analog of the spermine NONOate, spermine, was without effect. No evidence of cell death induced by any of the brief treatments with exogenous NO was observed; only prolonged incubation with much larger amounts of exogenous NO resulted in significant cell death. These data suggest that in vivo release of NO may cause elevations of intracellular Zn(2+) in cortical neurons. The possibility that release of intracellular Zn(2+) in response to NO could play a role in intracellular signaling is discussed. PMID- 17279326 TI - Influence of gender on tamoxifen-induced biochemical changes in serum of rats. AB - Tamoxifen, the widely prescribed drug in the prevention and therapy of breast cancer, may cause side effects which may be influenced by gender. The present study was undertaken to investigate the impact of gender on tamoxifen-induced toxic and biochemical changes following oral administration of tamoxifen at high dose level of 20 mg/kg once daily for a 2-week period in both male and female rats. The results showed marked increases in serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in female rats. In contrast, treatment with tamoxifen in male animals significantly decreased the activity of ALT, with a tendency for a decrease in serum AST levels. In female rats, a significant reduction in the serum activity of acid phosphatase (ACP) was noted, compared with a non-significant decrease in males. Non-significant changes in serum levels of alkaline phosphatase (ALP) were seen in both sexes. Tamoxifen lowered serum contents of total lipid and total cholesterol in both male and female rats. Serum levels of triglycerides were reduced in female rats as compared to a non-significant decrease in male animals. The serum albumin concentration was decreased in both male and female rats, while total protein was decreased only in female animals. Tamoxifen markedly increased serum levels of creatinine in female rats, compared with a non-significant rise in males. Total serum contents of calcium were similarly reduced in both males and females. This is the first study which points to gender-related differences in tamoxifen induced toxic and metabolic changes in rats. The results indicated that females are more susceptible than males to tamoxifen toxicity, probably due to the ability of tamoxifen to antagonize the action of estrogen in females. PMID- 17279327 TI - Using technology to enhance prevention services for children in primary care. AB - Primary care is the principal setting for implementation of prevention services for children and their families. However, aspects of primary care practice and lack of patient adherence to therapeutic regimens that ultimately lead to lifestyle and behavior changes are barriers to the delivery of prevention services. The authors of this paper present descriptive information about how a web-based computer application is being used to assist physicians in a major medical center overcome some of these impediments. This information is presented in the hopes of generating discussion about the utility of computer based support for prevention services in primary care settings. Additional steps to optimize the care of patients are also described. PMID- 17279328 TI - The effects of city-wide implementation of "second step" on elementary school students' prosocial and aggressive behaviors. AB - This study examined the impact of implementing Second Step, a violence prevention program, using a comprehensive, city-wide approach. The evaluation included 741 3rd-5th graders in six schools. Student surveys, behavioral observations, and discipline referrals were used to assess aggressive-antisocial and prosocial behaviors. We found significant improvements in positive approach-coping, caring cooperative behavior, suppression of aggression, and consideration of others, but no changes in aggressive-antisocial behaviors. Behavioral observations and disciplinary referrals showed no significant changes. The program was implemented with high fidelity and engaged a wide range of participants from the community. PMID- 17279329 TI - Risk perception, worry and satisfaction related to genetic counseling for hereditary cancer. AB - In this multi center study, genetic counseling for hereditary cancer was evaluated by assessing patients' worry, perceived risk of developing cancer and satisfaction with genetic counseling. An overall aim was to identify characteristics of vulnerable patients in order to customize genetic counseling. In addition, agreement between patients' and counselors' scores was measured. A total of 275 Norwegian patients were consecutively recruited, and 213 completed questionnaires before and after genetic counseling. Patients' perceived risk decreased after the genetic counseling session. There was incongruence between risk perception expressed as a percentage and in words. Patients were significantly less worried after counseling. Higher levels of worry were predicted by low instrumental satisfaction with counseling, high degree of perceived risk of developing cancer and younger age. In conclusion, counselors met the patients' psychological needs to a satisfactory degree during counseling. However, patients did not fully understand their risk of developing cancer. PMID- 17279330 TI - Nutrient intake, body composition, blood cholesterol and glucose levels among adult Asian Indians in the United States. AB - Asian Indian (AI) immigrants have been suggested to be at increased risk for chronic disease. This study examined the metabolic risk factors for CVD among AI immigrants participating in a health fair in Southern Michigan, in the U.S. Participants included AI men (n = 44) and women (n = 57) who completed a demographic questionnaire, blood lipid (TC and HDL-C) and blood glucose (BG) test, resting BP check (SBP and DBP), body composition analysis and 24-h diet recall. For the entire group, the mean values were: BMI = 25.5, % body fat (BF) = 29.3; SBP = 129 mmHg; DBP = 76 mmHg; TC = 198 mg/dL; HDL-C = 48 mg/dL; BG = 111 mg/dL. Significant gender differences were observed: % BF (20% vs. 36%, P < 0.0001), lean body mass (122 vs. 48 lbs, P < 0.0001), HDL-C (42 vs. 52 mg/dL, P < 0.0025), TC/HDL-C (4.86 vs. 4.11, P < 0.03) and BG (122 vs. 105 mg/dL, P < 0.0001), for males and females, respectively. Dietary carbohydrate, protein and fat contributed 64, 14 and 25% of total energy intake. Among males, BMI was positively correlated with % BF (0.729, P < 0.01) and negatively correlated with HDL-C (-0.457, P < 0.05). Among females, BMI was positively correlated with % BF (0.801, P < 0.01), SBP (0.425, P < 0.05) and DBP (0.538, P < 0.01), and negatively correlated with % energy from saturated fat (-0.523, P < 0.01) and calcium intake (-0.445, P < 0.05). Despite having a dietary intake that meets the National Cholesterol Education Program, Adult Treatment Panel III recommendations, this group was at a higher risk for chronic disease, by virtue of increased BMI and % BF along with an altered metabolic profile (high BP and TC and low HDL-C). PMID- 17279332 TI - Metal enhanced fluorescence solution-based sensing platform 2: fluorescent core shell Ag@SiO2 nanoballs. AB - In this Rapid Communication, we present the development of monodisperse core shell (silver core-silica shell) nanoparticles with various shell thicknesses featuring a fluorophore, subsequently named Metal-Enhanced Fluorescence (MEF) nanoballs. MEF nanoballs consist of a approximately 130 nm silver nanoparticle core, a silica shell with up to 35 nm thickness and fluorophores doped within the silica shell. Fluorescent nanobubbles where the silver core is removed by chemical etching are used as control samples to show the benefits of using silver nanoparticles, i.e, Metal-Enhanced Fluorescence. Finally, we demonstrate the broad potential biological applications of MEF nanoballs by employing near-infra red emitting probes (Rhodamine 800) within the silica shell, for potential applications in cellular imaging and solution-based sensing. PMID- 17279331 TI - The role of ammonium citrate washing on the characteristics of mechanochemical hydrothermal derived magnesium-containing apatites. AB - The role of citrate washing on the physical and chemical characteristics of magnesium-substituted apatites (HAMgs) was performed. HAMgs were synthesized by a mechanochemical-hydrothermal route at room temperature in as little as 1 h, which is five times faster than our previous work. Magnesium-substituted apatites had concentrations as high as 17.6 wt% Mg with a corresponding specific surface area (SSA) of 216 m(2)/g. A systematic study was performed to examine the influence of increasing magnesium content on the physical and chemical characteristics of the reaction products. As the magnesium content increased from 0 to 17.6 wt%, magnesium-doped apatite crystallite size decreased from 12 to 8.8 nm. The Mg/(Mg + Ca) ratio in the product was enriched relative to that used for the reacting precursor solution. During mechanochemical-hydrothermal reaction, magnesium doped apatites co-crystallize with magnesium hydroxide. Citrate washing serves to remove the magnesium hydroxide phase. The concomitant increase in surface area results because of the removal of this phase. Possible mechanisms for magnesium hydroxide leaching are discussed to explain the measured trends. PMID- 17279333 TI - Fluorescence analysis with quantum dot probes for hepatoma under one- and two photon excitation. AB - A new class of fluorescent probe produced by conjugating semiconductor quantum dots (QDs) with protein molecule is proposed as an alternative to conventional organic labels. However the fluorescence characteristics of the QD bioconjugates are not clear while they are excitied with one- or two-photon laser pulse. We synthesized specific immunofluorescent probes by linking QDs to alpha fetoprotein (AFP) antibody for specific binding alpha-fetoprotein -an important marker for hepatocellular carcinoma cell lines, and archived specific fluorescence detection with the QDs-Anti-AFP in nude mice. Then, we have analyzed the fluorescence characteristics of QDs-Anti-AFP and original QDs both under one- and two-photon excitations. The results demonstrated that QDs-Anti-AFP's fluorescent spectral and lifetime haven't varied much from that of original QDs. Moreover, QDs-Anti AFP have exhibited higher fluorescence efficiency than QDs under two-photon examination. PMID- 17279335 TI - Calcium ion-induced stabilization and refolding of agkisacutacin from Agkistrodon acutus venom studied by fluorescent spectroscopy. AB - Agkisacutacin isolated from the venom of Agkistrodon acutus is a coagulation factor IX / coagulation factor X-binding protein with marked anticoagulant- and platelet-modulating activities. Ca(2+) ion-induced stabilization and refolding of Agkisacutacin have been studied by following fluorescent measurements. Ca(2+) ions not only increase the structural stability of agkisacutacin against GdnHCl denaturation, but also induce its refolding. The GdnHCl-induced unfolding of the apo-agkisacutacin and the purified agkisacutacin is a single-step process with no detectable intermediate state. Ca(2+) ions play an important role in the stabilization of the structure of agkisacutacin. Ca(2+)-stabilized agkisacutacin exhibits higher resistance to GdnHCl denaturation than the apo-agkisacutacin. It is possible to induce refolding of the unfolded apo-agkisacutacin merely by adding 1 mM Ca(2+) ions without changing the concentration of the denaturant. The kinetic result of Ca(2+)-induced refolding provides evidences for that agkisacutacin consists of at least two refolding phases and the first phase of Ca(2+)-induced refolding should involve the formation of the compact Ca(2+) binding site regions, and subsequently, the protein undergoes further conformational rearrangements to form the native structure. PMID- 17279337 TI - International planning directions for provision of mental health services. AB - Internationally, there have been calls for more strategic mental health care delivery. For this to occur, individual countries need to define 'core' mental health services and set evidence-based, country-specific resource targets related to these. Via a web search, we identified 32 current mental health plans from five developed countries. We synthesised descriptive information from these documents, in order to compare profiles of 'core' services, resource targets relating to these services, and rationales for these resource targets. Most plans list 'core' clinical services, typically including a mix of inpatient and community services. Only four plans cite resource targets for these 'core' services, and these are difficult to compare due to different definitional and counting rules. All four provide rationales for the targets, though these vary in strength. The challenge remains for individual countries to develop plans that include appropriate resource targets, and to implement initiatives that move them towards these targets. PMID- 17279336 TI - Monitoring of the proton electrochemical gradient in reconstituted vesicles: quantitative measurements of both transmembrane potential and intravesicular pH by ratiometric fluorescent probes. AB - Proteoliposomes carrying reconstituted yeast plasma membrane H(+)-ATPase in their lipid membrane or plasma membrane vesicles are model systems convenient for studying basic electrochemical processes involved in formation of the proton electrochemical gradient (Deltamicro(H) (+)) across the microbial or plant cell membrane. Deltapsi- and pH-sensitive fluorescent probes were used to monitor the gradients formed between inner and outer volume of the reconstituted vesicles. The Deltapsi-sensitive fluorescent ratiometric probe oxonol VI is suitable for quantitative measurements of inside-positive Deltapsi generated by the reconstituted H(+)-ATPase. Its Deltapsi response can be calibrated by the K(+)/valinomycin method and ratiometric mode of fluorescence measurements reduces undesirable artefacts. In situ pH-sensitive fluorescent probe pyranine was used for quantitative measurements of pH inside the proteoliposomes. Calibration of pH sensitive fluorescence response of pyranine entrapped inside proteoliposomes was performed with several ionophores combined in order to deplete the gradients passively formed across the membrane. Presented model system offers a suitable tool for simultaneous monitoring of both components of the proton electrochemical gradient, Deltapsi and DeltapH. This approach should help in further understanding how their formation is interconnected on biomembranes and even how transport of other ions is combined to it. PMID- 17279334 TI - Fluorescent temporin B derivative and its binding to liposomes. AB - Temporins are short (10-13 amino acids) and linear antimicrobial peptides first isolated from the skin of the European red frog, Rana temporaria, and are effective against Gram-positive bacteria and Candida albicans. Similarly to other antimicrobial peptides, the association of temporins to lipid membranes has been concluded to underlie their antimicrobial effects. Accordingly, a detailed understanding of their interactions with phospholipids is needed. We conjugated a fluorophore (Texas Red) to a Cys containing derivative of temporin B (temB) and investigated its binding to liposomes by fluorescence spectroscopy. Circular dichroic spectra for the Cys-mutant recorded in the absence and in the presence of phospholipids were essentially similar to those for temB. A blue shift in the emission spectra and diminished quenching by ferrocyanide (FCN) of Texas Red labeled temporin B (TRC-temB) were seen in the presence of liposomes. Both of these changes can be attributed to the insertion of the Texas Red into the hydrophobic region of the bilayer. Resonance energy transfer, steady state anisotropy, and fluorescence lifetimes further demonstrate the interaction of TRC temB with liposomes to be enhanced by negatively charged phospholipids. Instead, cholesterol attenuates the association of TRC-temB with membranes. The interactions between TRC-temB and liposomes of varying negative surface charge are driven by electrostatics as well as hydrophobicity. Similarly to native temporin B also TRC-temB forms amyloid type fibers in the presence of negatively charged liposomes. This property is likely to relate to the cytotoxic activity of this peptide. PMID- 17279338 TI - The Latino mental health project: a local mental health needs assessment. AB - In this article, we present the results of a local needs assessment of the mental health experiences, service needs, and barriers to treatment-seeking of the Latino population in Worcester, Massachusetts. Overall, participants reported relatively high rates of experiences with symptoms of mental health problems, they indicated using a range of both formal and alternative mental health services, and they noted a variety of instrumental, attitudinal, and culturally specific barriers to seeking mental health services. Findings are discussed with regards to the role that community-driven research can play in advancing efforts to provide relevant services to underserved populations. PMID- 17279339 TI - The environments of adopted and non-adopted youth: evidence on range restriction from the Sibling Interaction and Behavior Study (SIBS). AB - Previous reviews of the literature have suggested that shared environmental effects may be underestimated in adoption studies because adopted individuals are exposed to a restricted range of family environments. A sample of 409 adoptive and 208 non-adoptive families from the Sibling Interaction and Behavior Study (SIBS) was used to identify the environmental dimensions on which adoptive families show greatest restriction and to determine the effect of this restriction on estimates of the adoptive sibling correlation. Relative to non adoptive families, adoptive families experienced a 41% reduction of variance in parent disinhibitory psychopathology and an 18% reduction of variance in socioeconomic status (SES). There was limited evidence for range restriction in exposure to bad peer models, parent depression, or family climate. However, restriction in range in parent disinhibitory psychopathology and family SES had no effect on adoptive-sibling correlations for delinquency, drug use, and IQ. These data support the use of adoption studies to obtain direct estimates of the importance of shared environmental effects on psychological development. PMID- 17279341 TI - Incremental validity of the psychological inventory of criminal thinking styles and psychopathy checklist: screening version in predicting disciplinary outcome. AB - A group of 136 male inmates housed in a medium security federal correctional institution were followed for a period of 24 months for evidence of disciplinary infractions (incident reports) after completing the Psychological Inventory of Criminal Thinking Styles (PICTS) and being scored on the Psychopathy Checklist: Screening Version (PCL:SV). Age, prior incident reports, the PICTS General Criminal Thinking (GCT) score, and the PCL:SV total score were included in a series of negative binomial regressions and Receiver Operating Characteristic (ROC) analyses of three increasingly more serious outcomes: total incident reports, major incident reports, and aggressive incident reports. Results indicated that the PICTS GCT score and PCL:SV total score were incrementally valid predictors of all three outcomes, with the strongest effects occurring when more severe incident reports were predicted. On the other hand, only the PICTS GCT score and Proactive Criminal Thinking (P) scale produced more than one significant ROC finding. PMID- 17279340 TI - Children's feedback preferences in response to an experimentally manipulated peer evaluation outcome: the role of depressive symptoms. AB - The present study examined the linkage between pre-adolescent children's depressive symptoms and their preferences for receiving positive vs. negative feedback subsequent to being faced with an experimentally manipulated peer evaluation outcome in real time. Participants (n = 142) ages 10 to 13, played a computer contest based on the television show Survivor and were randomized to either a peer rejection (i.e., receiving the lowest total 'likeability' score from a group of peer-judges), a peer success (i.e., receiving the highest score), or a control peer evaluation condition. Children's self-reported feedback preferences were then assessed. Results revealed that participants assigned to the negative evaluation outcome, relative to either the success or the control outcome, showed a significantly higher subsequent preference for negatively tuned feedback. Contrary to previous work and predictions derived from self verification theory, children higher in depressive symptoms were only more likely to prefer negative feedback in response to the negative peer evaluation outcome. These effects for depression were not accounted for by either state mood at baseline or mood change in response to the feedback manipulation. PMID- 17279342 TI - [An undiagnosed plasma cell myeloma. Complication after performing spinal anesthesia]. AB - A male patient developed neurological deficits after an uneventful spinal anesthesia. After 2 months without any improvement an epidural hematoma was presumed. Magnet resonance imaging detected inflammatory tissue and destruction at lumbar levels L2/3. The inflammatory tissue had to be removed via laminectomy. Histology of the excised tissue revealed a plasma cell myeloma that was not diagnosed prior to spinal anesthesia 2 months previously. PMID- 17279345 TI - [Beyond all words. First aid for the grieving and traumatised]. AB - The limits of the "language of (in) medicine" emerge more clearly when demanding situations occur. The confrontation with death is an experience which leads to speechlessness because the limitations of language coincide with a limitation of medicine. A qualified psychosocial support can, however, make a contribution in that the bereaved can be turned into mourners. With this in the background the demand for doctors to have a basic psychosocial competence is not an extravagent desire but a component of prevention. PMID- 17279343 TI - [Indocyanine green plasma disappearance rate. Marker of partial hepato-splanchnic ischemia]. AB - Indocyanine green (ICG) is nearly exclusively eliminated from the blood by the liver and the ICG plasma disappearance rate (ICG-PDR) enables assessment of liver blood flow and function. The ICG-PDR which nowadays can be measured non invasively by a transcutaneous system enables bedside and "on-line" regional monitoring in critically ill patients. So far, only complete lack of ICG-PDR as a sign of non-existing perfusion during liver transplantation has been reported. We describe two patients who developed mesenteric ischemia accompanied by an inadequate increase after revascularisation and an acute drop in the ICG-PDR. In both cases, a computed tomography scan was performed and confirmed an acute abdominal ischemia as indicated by ICG-PDR. Both patients suffered from occlusion of the truncus coeliacus while hepato-splanchnic perfusion via the A. mesenterica superior and the V. portae was maintained. ICG-PDR may be helpful for early detection of hepato-splanchnic ischemia and enables rapid and sufficient initiation of diagnostic and therapeutic procedures. In conclusion, ICG-PDR may be regarded as a clinically attractive bedside monitoring tool for early and reliable detection of partial ischemia in the hepato-splanchnic tract. PMID- 17279347 TI - Properties of scyllo-inositol as a therapeutic treatment of AD-like pathology. AB - Inositol is a simple polyol with eight naturally occurring stereoisomers. myo Inositol, D-chiro- and epi-inositol have been examined as potential therapeutic agents for various diseases, with favorable results, but treatment with scyllo inositol has not been previously investigated. Our laboratory has shown that scyllo-inositol inhibits cognitive deficits in TgCRND8 mice and significantly ameliorates disease pathology, suggesting it might be effective in treating Alzheimer's disease (AD). In this paper, we show that scyllo-inositol has a sustained ability to treat animals at advanced stages of AD-like pathology. Significant decreases in insoluble Abeta40, Abeta42, and plaque accumulation were observed in the brains of treated versus untreated TgCRND8 mice. The growth of plaques of all sizes was inhibited by scyllo-inositol administration. To demonstrate that the scyllo-inositol effects were within the CNS, gas chromatography/mass spectrometry was used to examine myo- and scyllo-inositol concentrations after oral administration. Further, we examined how closely scyllo and myo-inositol are inter-regulated in the CNS and whether scyllo-inositol, if elevated within the CNS, would incorporate into phosphatidylinositol lipids. Cerebral spinal fluid levels of scyllo-inositol increased after scyllo-inositol treatment but not myo-inositol treatment. scyllo-Inositol treatment also caused increased levels of scyllo-inositol in the brain. We further show that scyllo inositol, even at elevated levels, does not incorporate into the phosphatidylinositol family of lipids. These combined results demonstrate that scyllo-inositol accumulates within the CNS up to tenfold endogenous levels and does not interfere with phosphatidylinositol lipid production. PMID- 17279348 TI - Small-cell anal carcinoma and AIDS: case report and review of the literature. PMID- 17279346 TI - SREBP-1c and TFE3, energy transcription factors that regulate hepatic insulin signaling. AB - Genes involved in carbohydrate and lipid metabolism are nutritionally regulated at the transcriptional level in a coordinated fashion. SREBP-1c is a bHLH transcription factor that controls lipogenesis and is induced during overnutrition to facilitate the conversion of glucose to fatty acids and triglycerides for the storage of the excess energy. Uncontrolled activation of nuclear SREBP-1c in the liver can cause hepatosteatosis, hypertriglyceridemia, and hepatic insulin resistance due to direct suppression of insulin signaling pathways, precipitating development of metabolic syndrome. Conversely, TFE3 is a novel bHLH transcription factor that strongly activates various insulin signaling molecules, protecting against the development of insulin resistance and the metabolic syndrome. Regulation of IRS-2 is the primary site where TFE3 in synergy with Foxo1, and SREBP-1c converge. Taken together, TFE3/Foxo1 and SREBP-1c reciprocally regulate IRS-2 expression and insulin sensitivity in the liver. This scenario provides a mechanistic explanation for the physiological link between glucose and lipid metabolism such as physiological switching of glycogen synthesis to lipogenesis. In addition, these two transcription factors may ultimately contribute to pathophysiological effects of overnutrition leading to the development of the metabolic syndrome and diabetes. In this review, I will discuss roles of SREBP-1c and TFE3 in homeostasis of energy metabolism and in metabolic disturbances, focusing on hepatic insulin sensitivity. PMID- 17279349 TI - Adenocarcinoma after restorative proctocolectomy for cancer in ulcerative colitis. PMID- 17279351 TI - Nurse plants, tree saplings and grazing pressure: changes in facilitation along a biotic environmental gradient. AB - Current conceptual models predict that an increase in stress shifts interactions between plants from competitive to facilitative; hence, facilitation is expected to gain in ecological importance with increasing stress. Little is known about how facilitative interactions between plants change with increasing biotic stress, such as that incurred by consumer pressure or herbivory (i.e. disturbance sensu Grime). In grazed ecosystems, the presence of unpalatable plants is reported to protect tree saplings against cattle grazing and enhance tree establishment. In accordance with current conceptual facilitation-stress models, we hypothesised a positive relationship between facilitation and grazing pressure. We tested this hypothesis in a field experiment in which tree saplings of four different species (deciduous Fagus sylvatica, Acer pseudoplatanus and coniferous Abies alba, Picea abies) were planted either inside or outside of the canopy of the spiny nurse shrub Rosa rubiginosa in enclosures differing in grazing pressure (low and high) and in exclosures. During one grazing season we followed the survival of the different tree saplings and the level of browsing on these; we also estimated browsing damage to the nurse shrubs. Shrub damage was highest at the higher grazing pressure. Correspondingly, browsing increased and survival decreased in saplings located inside the canopy of the shrubs at the high grazing pressure compared to the low grazing pressure. Saplings of both deciduous species showed a higher survival than the evergreens, while sapling browsing did not differ between species. The relative facilitation of sapling browsing and sapling survival - i.e. the difference between saplings inside and outside the shrub canopy - decreased at high grazing pressure as the facilitative species became less protective. Interestingly, these findings do not agree with current conceptual facilitation-stress models predicting increasing facilitation with abiotic stress. We used our results to design a conceptual model of facilitation along a biotic environmental gradient. Empirical studies are needed to test the applicability of this model. In conclusion, we suggest that current conceptual facilitation models should at least consider the possibility of decreasing facilitation at high levels of stress. PMID- 17279350 TI - Follow-up after colorectal polypectomy: a benefit-risk analysis of German surveillance recommendations. AB - OBJECTIVE: For colorectal screening patients a mean gain of life time was previously calculated of about 30-50 days. Different recommendations for recognising at-risk groups and defining surveillance intervals after an initial finding of colorectal adenomas have been published. However, no benefit-risk analysis regarding to specific long-term effects of follow-up has been reported to date. MATERIALS AND METHODS: A Markov model based on time-dependent transition possibilities was developed to perform a benefit-risk analysis of the risk related surveillance recommendations based on the Erlangen Registry of Colorectal Polyps (ERCRP) in comparison with the recommendation of the German Society of Gastrointestinal Diseases and Nutrition (DGVS). The outcome was calculated for a 50-year-old patient with 30 years of follow-up after initial polypectomy. The data used in this model were taken from different sources, namely the ERCRP, the German Study Group of Colorectal Cancer, the German Statistical Yearbook, and from meta-analyses of studies reporting data on complications and sensitivity of colonoscopy. RESULTS: Patients under surveillance have a mean lifetime gain of 98 (ERCRP) and 110 (DGVS) days compared with those who do not come for surveillance. 84% and 94% of deaths from colorectal carcinoma (CRC) could be prevented if patients were followed up according to the recommendations of the ERCRP and the DGVS, respectively. Less colonoscopies are needed to prevent one death from CRC following the recommendations of the ERCRP (221) than those of the DGVS (283). The risk of death due to colonoscopy for patients during follow-up is about 0.05% lifetime risk. Sensitivity analysis showed the stability of the results under a wide range of reasonable variations of relevant parameters. In a pessimistic one way sensitivity analysis regarding compliance, effectiveness was reduced to one third. CONCLUSION: Surveillance using colonoscopy is an effective tool for preventing CRC after colorectal polypectomy, especially if a good compliance is assumed. The effectiveness is higher following the recommendations of the DGVS, but more colonoscopies are needed. PMID- 17279352 TI - A novel mechanism of action for statins against diabetes-induced oxidative stress. AB - AIMS/HYPOTHESIS: Atorvastatin exerts beneficial vascular effects in diabetes, but the underlying mechanisms are yet to be elucidated. The aim of the present study was to determine whether Rac-1 is involved in the effect of atorvastatin on oxidative stress and vascular dysfunction. MATERIALS AND METHODS: Using human aortic endothelial cells (HAECs) we evaluated the effect of high glucose levels on peroxide production by dihydrodichlorofluorescein and on Rac-1 activity using immunocytochemistry to detect Rac-1 translocation to the membrane. We evaluated vascular function, peroxide production by dihydroethidium and NADPH oxidase activity in vessels from atorvastatin-treated mice. Rac-1 activity was also assessed, both by immunoprecipitation of the Rac-p21-activated kinase complex and by analysis of Rac-1 translocation to the membrane. These experiments were also conducted in vessels infected with an adenoviral vector carrying a constitutively active mutant of Rac-1. RESULTS: In HAECs exposed to high glucose levels, atorvastatin prevented oxidative stress, and this protection was associated with impaired Rac-1 activation. This effect was also observed in a murine model of diabetes mellitus. More importantly, the addition of geranylgeranyl pyrophosphate (GGPP) blocked the effects of atorvastatin in both glucose-exposed HAECs and diabetic vessels. Atorvastatin failed to afford protection against vascular abnormalities in the presence of a constitutively active mutant of Rac-1. CONCLUSIONS/INTERPRETATION: The results of this study demonstrate that the vascular antioxidant effect of atorvastatin in diabetes is mediated through inhibition of Rac-1 via a reduction in GGPP. Thus, selective Rac-1 inhibition should be considered in the design of novel pharmacological strategies to reduce the impact of diabetes mellitus on vascular function. PMID- 17279353 TI - Mitochondrial function: use it or lose it. PMID- 17279355 TI - Comments to the letter to the editors by Naunton. PMID- 17279354 TI - C-reactive protein induces phosphorylation of insulin receptor substrate-1 on Ser307 and Ser 612 in L6 myocytes, thereby impairing the insulin signalling pathway that promotes glucose transport. AB - AIMS/HYPOTHESIS: C-reactive protein (CRP) is associated with insulin resistance and predicts development of type 2 diabetes. However, it is unknown whether CRP directly affects insulin signalling action. To this aim, we determined the effects of human recombinant CRP (hrCRP) on insulin signalling involved in glucose transport in L6 myotubes. MATERIALS AND METHODS: L6 myotubes were exposed to endotoxin-free hrCRP and insulin-stimulated activation of signal molecules, glucose uptake and glycogen synthesis were assessed. RESULTS: We found that hrCRP stimulates both c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2 activity. These effects were paralleled by a concomitant increase in IRS-1 phosphorylation at Ser(307) and Ser(612), respectively. The stimulatory effects of hrCRP on IRS-1 phosphorylation at Ser(307) and Ser(612) were partially reversed by treatment with specific JNK and ERK1/2 inhibitors, respectively. Exposure of L6 myotubes to hrCRP reduced insulin-stimulated phosphorylation of IRS-1 at Tyr(632), a site essential for engaging p85 subunit of phosphatidylinositol-3 kinase (PI-3K), protein kinase B (Akt) activation and glycogen synthase kinase-3 (GSK-3) phosphorylation. These events were accompanied by a decrease in insulin-stimulated glucose transporter (GLUT) 4 translocation to the plasma membrane, glucose uptake and glucose incorporation into glycogen. The inhibitory effects of hrCRP on insulin signalling and insulin-stimulated GLUT4 translocation were reversed by treatment with JNK inhibitor I and the mitogen activated protein kinase inhibitor, PD98059. CONCLUSIONS/INTERPRETATION: Our data suggest that hrCRP may cause insulin resistance by increasing IRS-1 phosphorylation at Ser(307) and Ser(612) via JNK and ERK1/2, respectively, leading to impaired insulin-stimulated glucose uptake, GLUT4 translocation, and glycogen synthesis mediated by the IRS-1/PI-3K/Akt/GSK-3 pathway. PMID- 17279357 TI - Use of anti-asthmatic drugs during pregnancy. 3. Congenital malformations in the infants. AB - OBJECTIVE: To study the risk for congenital malformations among infants whose mothers used anti-asthmatic drugs during pregnancy. MATERIALS AND METHODS: We studied 24,750 infants whose mothers reported the use of anti-asthmatic drugs in early pregnancy. Infants were identified from the Swedish Medical Birth Register where drug use reported at the first maternal health care visit is recorded. Congenital malformations among the infants born were identified from that register, the Swedish Register of Congenital Malformations, and the Hospital Discharge Register. Rates of malformations among infants exposed to anti asthmatics were compared with the background population rate of malformations (4.7%) after adjustment for year of birth, maternal age, parity, smoking, and previous miscarriages. RESULTS: A weak increase in the risk for a congenital malformation was seen (odds ratio =1.09, 95% CI=1.03-1.15) which could not be explained by the confounders studied. The risks for three specific types of malformations appeared to be increased: relatively severe cardiac defects, orofacial clefts and specifically median cleft palate, and anal atresia. For the two last mentioned groups, use of anti-asthmatics with inhaled corticosteroids showed a higher odds ratio than use of other anti-asthmatics, but the differences could be random. CONCLUSIONS: Maternal asthma and use of anti-asthmatic drugs carry no major risk for congenital malformations in the offspring, but a slight teratogenic effect cannot be excluded. It may be due to asthma, and arguments for a stronger effect of inhaled corticosteroids than of other anti-asthmatics are weak. PMID- 17279356 TI - Prescribing pattern of antihypertensive drugs in primary care units in Turkey: results from the TURKSAHA study. AB - OBJECTIVES: The prescribing pattern of drugs used for treating hypertension changes over time in response to changes in recommended guidelines and innovations in drug formulations, among others. In addition, the classes of antihypertensive drugs used vary among the countries. The aim of this study was to investigate the practice of antihypertensive medications in primary care units in Turkey. METHOD: TURKSAHA is a cross-sectional screening study conducted in 1000 primary care units considered to be representative of primary care in Turkey, with the purpose of defining the demographic characteristics, clinical features, rate of blood pressure control achieved and the antihypertensive drugs prescribed for the hypertensive patients treated in these centers. In this analysis, we investigated the agents used in the treatment regimen. RESULTS: Of the 16,270 patients considered to be eligible for inclusion in the study, 15,187 (93.3%) were on an antihypertensive treatment, and 1083 (6.7%) were receiving no treatment. Patients who received treatment but whose antihypertensive medication was not specified (2290 patients) were subsequently excluded, and the trial was carried out with the remaining 12,897 patients. The mean age of the patients was 60 +/- 11 years (60.2% female). Of the 12,897 patients, 75.7% were receiving monotherapy, 19.7% two drugs, 4.1% three drugs and 0.5% four or more drugs. The rate of successful blood pressure control (<140/90 mmHg; for diabetics <130/80 mm Hg) in relation to the number of drugs received was 26.3, 25.9, 24.5 and 26.2%, respectively. Among the patients receiving monotherapy, the most frequently used antihypertensive drug class was angiotensin-converting enzyme inhibitors (30.1%), followed by beta-blockers (20.6%), calcium-channel blockers (17.9%), diuretics (15.4%) and angiotensin-receptor blockers (14%). CONCLUSION: As in other European countries, the rate of successful blood pressure control was low among hypertensive patients receiving treatment, and despite the inadequacy of monotherapy to control blood pressure, many of the patients continued this treatment regimen. Consistent with the global trend, the most frequently prescribed anti-hypertensives were angiotensin blockers. PMID- 17279359 TI - Twenty years after the Chernobyl accident: solid cancer incidence in various groups of the Ukrainian population. AB - Several major international studies such as those performed on the A-bomb survivors, have shown a clear linkage between the exposure to ionizing radiation and the occurrence of various cancer types including leukemia. While these studies are mostly characterized by high dose rates, studies on populations exposed after the Chernobyl accident are in most cases characterized by low dose rates which are typical for occupational radiation protection. Here, data on more than 60,000 Ukrainian workers who participated in recovery operation works in Chernobyl in 1986-1987, more than 50,000 evacuees from the city of Prypyat and the 30 km zone, and about 360,000 residents of most contaminated territories are presented, which cover a period of observation from 1980 to 2004. For all cancers combined, statistically significant higher incidence rates than the national rates were found only for the recovery workers (standardized incidence ratio (SIR) 117.2%, 95% confidence interval: 114.1-120.3), while those for the other investigated groups were lower. In all groups under study a significant increase of thyroid cancer incidence rates has been registered. This increase appears to be associated, at least partly, with the fallout of radioiodine, and it was found not only in children, but also in adolescents and adults. For example, the most significant excess was found for male recovery workers corresponding to a factor of 8.0. It is important to keep in mind, however, that the contribution of confounding factors such as an intensified thyroid screening after the Chernobyl accident could not be quantified, in the present study. For female recovery workers there was also an excess of breast cancer over the national rates (SIR 190.6%; 95% confidence interval: 163.6-217.7%). An analysis of the two other groups (evacuees and residents of contaminated territories) gave controversial results: relative to the local standard there was a statistically significant excess, while comparison with the national level did not substantiate this conclusion. PMID- 17279358 TI - UVB induced oxidative stress in human keratinocytes and protective effect of antioxidant agents. AB - This study aims at exploring the oxidative stress in keratinocytes induced by UVB irradiation and the protective effect of nutritional antioxidants. Cultured Colo 16 cells were exposed to UVB in vitro followed by measurement of reactive oxygen species (ROS), endogenous antioxidant enzyme activity, as well as cell death in the presence or absence of supplementation with vitamin C, vitamin E, or Ginsenoside Panoxatriol. Intracellular ROS content was found significantly reduced 1 h after exposure, but increased at later time points. After exposure to 150-600 J m(-2) UVB, reduction of ROS content was accompanied by increased activity of catalase and CuZn-superoxide dismutase at early time points. Vitamins C and E, and Ginsenoside Panoxatriol counteracted the increase of ROS in the Colo 16 cells induced by acute UVB irradiation. At the same time, Ginsenoside Panoxatriol protected the activity of CuZn-superoxide dismutase, while vitamin E showed only a moderate protective role. Vitamins C and E, and Ginsenoside Panoxatriol in combination protected the Colo-16 cells from UVB-induced apoptosis, but not necrosis. These findings suggest that vitamins C and E as well as Ginsenoside Panoxatriol are promising protective agents against UVB-induced damage in skin cells. PMID- 17279361 TI - In response to Isbister et al.: Application of pharmacokinetic-pharmacodynamic modeling in management of QT abnormalities after citalopram overdose. PMID- 17279363 TI - Does menstrual cycle effect buffer capacity of stimulated saliva? AB - The present study was performed to analyze buffer capacity (BC) and flow rate of stimulated saliva during menstrual cycle. Two salivary samples were taken from 17 subjects during the menstrual cycle. BC was determined according to electrometric method. Both variables showed no hormone dependency. The results suggest that the salivary protection against acid attacks is constant in healthy nonpregnant women. PMID- 17279362 TI - Periodic acceptor excitation spectroscopy of single molecules. AB - Alternating-laser excitation (ALEX) spectroscopy has recently been added to the single-molecule spectroscopy toolkit. ALEX monitors interaction and stoichiometry of biomolecules, reports on biomolecular structure by measuring accurate Forster resonance energy transfer (FRET) efficiencies, and allows sorting of subpopulations on the basis of stoichiometry and FRET. Here, we demonstrate that a simple combination of one continuous-wave donor-excitation laser and one directly modulated acceptor-excitation laser (Periodic Acceptor eXcitation) is sufficient to recapitulate the capabilities of ALEX while minimizing the cost and complexity associated with use of modulation techniques. PMID- 17279365 TI - Improved yielding and reduced puffiness under extreme temperatures induced by fruit-specific expression of rolB in processing tomatoes. AB - Tomato fruit production is severely hampered by both extremely high and low temperatures, mainly due to impaired microsporogenesis and pollination under these conditions. Even mild temperature stress, leading to partial damage to pollen viability can result in the production of under-fertilized puffy fruits of poor quality, while severe stress can abolish fruit set completely. Genetic or transgenic parthenocarpy that enables fertilization-independent fruit development offers a solution for tomato yielding under conditions unfavorable for pollen production and/or fertilization. A transgenic processing tomato UC82 line, expressing rolB specifically during early stages of fruit development was compared to the parental line with respect to yield and fruit quality under extreme temperatures. Under both high and low temperatures the transgenic line performed significantly better than the parental line. Its yield was significantly higher mainly due to a higher number of fruits that did develop, and also because of increased fruit weight. While the UC82 fruits developed under high temperatures were very puffy and severely malformed, the transgenic fruits maintained improved jelly fill and were of smooth and regular shape. Interestingly, under high temperatures the improved jelly fill in the transgenic line was accompanied by a higher number of seeds, suggesting that not only the developing seeds promote development of the placental tissue but also that proliferation of this tissue supports better seed development. PMID- 17279364 TI - Vascular endothelial growth factor (VEGF) levels of gingiva and gingival crevicular fluid in diabetic and systemically healthy periodontitis patients. AB - It has been demonstrated that diabetes mellitus (DM) may have an inductive effect on the vascular endothelial growth factor (VEGF) levels of periodontium during periodontal disease. The aim of this study is to confirm this phenomenon, investigating whether it is also valid for diabetic periodontitis patients under good metabolic control. Sixteen type II DM patients, all with a glycosylated hemoglobin (HbA1c) value less than 7 (test), and 15 systemically healthy (control) chronic periodontitis patients were included in the study. The VEGF concentrations in the gingival supernatants and gingival crevicular fluid (GCF) samples of the study groups were measured by enzyme-linked immunosorbent assay. The data were analyzed by Student's t test in statistical means. The VEGF levels were significantly higher in the gingival supernatants of the test group (55.89 +/- 8.11 pg/ml) than that of the control group (24.81 +/- 2.04 pg/ml; p < 0.01). However, there was no statistically significant difference in the VEGF levels of GCF between the study groups (38.96 +/- 4.89 pg/ml in the test and 32.20 +/- 4.02 pg/ml in the control group; p > 0.05). Our study confirms that DM affects the VEGF levels of periodontal soft tissues in periodontal disease, and our results also suggest that this effect may not be influenced by the metabolic control of DM. PMID- 17279366 TI - The Horn of Africa as a centre of barley diversification and a potential domestication site. AB - According to a widely accepted theory on barley domestication, wild barley (Hordeum vulgare ssp. spontaneum) from the Fertile Crescent is the progenitor of all cultivated barley (H. vulgare ssp. vulgare). To determine whether barley has undergone one or more domestication events, barley accessions from three continents have been studied (a) using 38 nuclear SSR (nuSSRs) markers, (b) using five chloroplast SSR (cpSSR) markers yielding 5 polymorphic loci and (c) by detecting the differences in a 468 bp fragment from the non-coding region of chloroplast DNA. A clear separation was found between Eritrean/Ethiopian barley and barley from West Asia and North Africa (WANA) as well as from Europe. The data from chloroplast DNA clearly indicate that the wild barley (H. vulgare ssp. spontaneum) as it is found today in the "Fertile Crescent" might not be the progenitor of the barley cultivated in Eritrea (and Ethiopia). Consequently, an independent domestication might have taken place at the Horn of Africa. PMID- 17279367 TI - Fine mapping of pss1, a pollen semi-sterile gene in rice (Oryza sativa L.). AB - During routine seed increase procedures in rice, semi-sterile plants are common; however, such semi-sterility mutants in rice varieties have been only rarely analyzed genetically. W207-2 is a semi-sterile selection from the japonica rice variety Nipponbare. In this report, we found the female gamete of W207-2 was normal, and its semi-sterility was unaffected by growth duration but was conditioned by a recessive nuclear gene whose action leads to pollen semi sterility and anther indehiscence, and the gene was named as pss1 (pollen semi sterile). Using an F(2) population derived from the two parents W207-2 and Dular and a pooled DNA strategy, pss1 was mapped to an interval on chromosome 8 defined by the two SSR loci RM6356 and RS41. The position of pss1 was confirmed in another F(2) population derived from the cross W207-2 x Nipponbare. Over 2,000 homozygous pss1 segregants from the large W207-2 x Dular F(2) population were used to fine map pss1 to a 0.04 cM segment flanked by a CAPs marker L2 and a dCAPs L3 marker. Sequences for both markers are present on a single PAC clone, and the physical distance between them is about 28 kb. Analysis of the PAC sequence predicts the presence of five open reading frames, they are as follows: putative ribonuclease PH, putative avr9 elicitor response protein, kinesin1-like protein, putative protein RNP-D precursor and putative 40S ribosomal protein S13. This result would be helpful in cloning the pss1 gene. PMID- 17279369 TI - Endoscopically assisted release for exertional compartment syndromes of the lower leg. AB - BACKGROUND: Endoscopic treatment of intractable chronic anterior and lateral exertional compartment syndromes of the lower leg in athletes is reported anecdotically only in six patients. HYPOTHESIS: H(0) = There is no difference between preoperative and postoperative status after endoscopic release of chronic exertional compartment syndromes of the lower leg. STUDY DESIGN: Case series; level of evidence, 4. METHODS: We developed a minimally invasive, endoscopically assisted technique for release of chronic exertional compartment syndromes of the lower leg. All patients were investigated by telephone interview 47 months (range 5 months-7 years) after surgery. RESULTS: This investigation comprises release of 19 deep posterior, 16 anterior, and 3 lateral compartments in 17 athletes. No complications were seen following endoscopic anterior and lateral compartment decompression, while two patients following deep posterior compartment release underwent open revision surgery due to hemorrhage. Initial endoscopic surgery in these two patients was performed under tourniquet. There were no postoperative complications due to vascular injuries in all further patients who were operated without tourniquet. Ten patients returned to previous sport activity. At follow up, results were good or excellent in 10 out of 17 patients. Visual analogue pain scale ranged from 5 to 9 (mean 7.4) before surgery and from 1 to 8 (mean 2.4) at follow up (P = 0.0005). CONCLUSIONS: This study confirms feasibility of endoscopic release for chronic exertional compartment syndromes of the lower leg on a larger scale. At least for the deep posterior compartment its safety and effectiveness cannot be recommended without stint as results are inferior as compared to data obtained from literature for open surgery. To avoid vascular complications, especially during deep posterior compartment fasciotomy it is most important to perform the procedure without tourniquet. PMID- 17279368 TI - "The Disappearing Patella": an unusual sequel following total knee replacement. AB - Patello femoral complications have been described following total knee replacement (TKR) surgery. Majority of the reports are on the position and the biomechanics across the patello femoral joint. An unusual finding which shows the patella to be gradually disappearing following a TKR has not been reported. We report this finding in a 74-year-old lady who underwent a right total knee replacement (TKR) 5 years ago. Check radio graphs taken at 2 years showed osteolysis and on follow up at 5 years the right patella has become very thin and appears to be disappearing. The right patella measured 17 mm (anterior posterior thickness) at time of surgery and now measures 4 mm. There is osteolysis adjacent to the tibial and femoral components. However, there are no features of infection and there is no history of trauma. The patient continues to be asymptomatic and mobilises with a normal pain free gait. This interesting and unusual sequel is being reported for its rarity. A similar finding following a TKR has not been cited in literature. PMID- 17279370 TI - Assessing leg length discrepancy following elastic stable intramedullary nailing for paediatric femoral diaphyseal fractures. AB - INTRODUCTION: Femoral overgrowth is a recognised phenomenon following fractures of the femoral diaphysis in children. This study was designed to assess leg length discrepancy (LLD) following elastic stable intramedullary nailing (ESIN) and its clinical significance. MATERIALS AND METHODS: A retrospective review of children who underwent ESIN with DePuy ACE Nancy nails between 1997 and 2001 for diaphyseal femoral fractures. Evaluation was by questionnaire, clinical examination and radiological measurement. RESULTS: 17/26 (65%) patients were followed up for a mean time of 48 months (21-77). Average age at surgery was 9 years. Mean operative time was 78 min with a mean hospital stay of 7.8 days. Mean time to union was 10 weeks. A statistically significant LLD of +3.2 mm is demonstrated in children aged 4-8 years (P = 0.05). LLD is not statistically significant in children over 8 years. CONCLUSION: ESIN is a successful treatment for paediatric diaphyseal femoral fractures and allows early mobilisation and discharge. A statistically significant LLD is observed in children aged 4-8 years although clinically only one patient in the entire series was aware of a leg length discrepancy. In addition clinical methods of leg length measurement are sensitive for LLD and we conclude that routine radiographic follow up is not necessary unless clinically indicated. PMID- 17279371 TI - A molecular modeling study on the enantioselectivity of aryl alkyl ketone reductions by a NADPH-dependent carbonyl reductase. AB - Automated structural analysis of Sporobolomyces salmonicolor carbonyl reductase (SSCR) indicates that the two largest potential receptor sites are in the vicinity of the nicotinamide reductant. The largest receptor site is a scalene triangle with sides of approximately 8 A by 9 A by 13 A, which is narrow in width; one corner is surrounded by hydrophilic residues that can favorably bond with the ketone oxygen. Docking aryl alkyl ketones shows a distinct preference for binding to the largest receptor site, and for conformations that place the carbonyl oxygen of the substrate in the hydrophilic corner of the largest receptor site. Favorable docking conformations for aryl alkyl ketones fall into two low-energy ensembles. These conformational ensembles are distinguished by the positions of the substituents, presenting either the Si- or Re-face of the ketone to the nicotinamide reductant. For the ketones investigated here, there is a correspondence between the major enantiomer of the alcohol obtained from the reduction of the ketone and the conformer found to have the most stable interaction energy with the receptor site in all cases. The receptor site modeling, docking simulations, molecular dynamics, and enzyme-substrate geometry optimizations lead to a model for understanding the enantioselectivity of this NADPH-dependent carbonyl reductase. PMID- 17279372 TI - Changes in multifocal oscillatory potentials after internal limiting membrane removal for macular hole: multifocal OPs after ILM removal. AB - PURPOSE: To determine whether removal of the internal limiting membrane (ILM) during macular hole (MH) surgery alters the retinal function. METHODS: Multifocal electroretinograms (mfERGs) were recorded preoperatively and 3 months after surgery from 11 eyes of 10 patients with an idiopathic MH treated successfully by pars plana vitrectomy accompanied by ILM removal. A low frequency (9.4 Hz) pseudorandom binary m-sequence stimulus was used to elicit the mfERGs from different retinal loci. The bandpass of the amplifier was set at 10-300 Hz to record the mfERGs and at 100-300 Hz to record the oscillatory potentials (OPs). RESULTS: An anatomical closure of the MH was achieved in all patients, and the mean visual acuity was significantly improved postoperatively. No significant difference was observed in both the amplitudes and implicit times of the negative and positive waves of the mfERGs and the OPs recorded preoperatively to those recorded postoperatively. CONCLUSIONS: MH surgery with ILM removal does not alter the electrophysiological function of both the outer and inner retina of the posterior pole where the ILM was removed. PMID- 17279374 TI - Clozapine and prazosin slow the rhythm of head movements during focused stereotypy induced by d-amphetamine in rats. AB - RATIONALE: Clozapine is an efficacious, symptom-ameliorating, atypical antipsychotic drug with few extrapyramidal side effects. Clozapine has been reported either not to affect or to increase d-amphetamine-induced stereotypy, a behavior that is blocked by typical antipsychotic drugs. OBJECTIVES: This work used a high-resolution measurement system to reassess clozapine's effects on d amphetamine-induced focused stereotypy (FS) in rats. MATERIALS AND METHODS: A force-plate actometer permitted the quantitation of the rhythm and vigor of movements during FS. Eight rats received a sensitizing series of doses of 5.0 mg/kg d-amphetamine sulfate, and this dosing regimen induced head movements with a rhythm near 10 Hz. Thirty minutes after d-amphetamine treatment, rats received acute clozapine (2.5-10.0 mg/kg), followed by eight, daily clozapine injections (5.0 mg/kg) given with d-amphetamine on days 2, 5, and 8. Effects of acute doses of the alpha1-noradrenergic antagonist prazosin (0.5-2.0 mg/kg) on the d amphetamine response were also examined. RESULTS: Clozapine dose-dependently slowed the near 10-Hz rhythm and reduced the vigor of the d-amphetamine-induced FS. Clozapine significantly lengthened the duration of the FS phase, but the rhythm remained slowed. No evidence for tolerance to clozapine's rhythm-slowing effects was seen in the subchronic phase. Prazosin dose-dependently reduced the near 10-Hz rhythm induced by d-amphetamine, but prazosin did not lengthen the FS phase. CONCLUSIONS: The results show that clozapine diminished the rhythm and vigor of d-amphetamine-induced stereotyped head movements but, at the same time, lengthened the duration of the expression of the stereotypy. alpha1 antagonism is a likely contributor to the rhythm-modulating effects of clozapine. PMID- 17279375 TI - Alcohol cues increase cognitive impulsivity in individuals with alcoholism. AB - BACKGROUND: Individuals with alcoholism are characterized by both attentional bias for alcohol cues and prepotent response inhibition deficit. We tested the hypothesis that alcoholics exhibit greater cognitive disinhibition when the response to be suppressed is associated with alcohol-related information. METHODS: Forty recently detoxified individuals with alcoholism were compared with 40 healthy non-substance abusers on the "Alcohol-Shifting Task", a variant of the go/no-go paradigm requiring a motor response to targets and no response to distracters. The aim was to test the ability of alcoholics to discriminate between alcohol-related and neutral words. Sometimes, the alcohol-related words were the targets for the "go" response, with neutral words as distracters, sometimes the reverse. Several shifts in target type occurred during the task. RESULTS: Alcoholics made significantly more commission errors (i.e., press a key when a distracter displayed) and more omission errors (i.e., not press a key when a target displayed) than controls. Moreover, the number of commission errors was greater in alcoholics when alcohol-related stimuli had to be detected. CONCLUSIONS: These results demonstrate that alcoholics exhibit a basic prepotent response inhibition deficit, which is enhanced when the response to be suppressed is related to alcohol. We discuss clinical and theoretical implications of these findings. PMID- 17279373 TI - Alterations in prefrontal glutamatergic and noradrenergic systems following MK 801 administration in rats prenatally exposed to methylazoxymethanol at gestational day 17. AB - RATIONALE: Prenatal methylazoxymethanol (MAM) administration at gestational day 17 has been shown to induce in adult rats schizophrenia-like behaviours as well as morphological and/or functional abnormalities in structures such as the hippocampus, medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc), consistent with human data. OBJECTIVES: The aim of the present study was to further characterize the neurochemical alterations associated with this neurodevelopmental animal model of schizophrenia. MATERIALS AND METHODS: We performed simultaneous measurements of locomotor activity and extracellular concentrations of glutamate, dopamine and noradrenaline in the mPFC and the NAcc of adult rats prenatally exposed to MAM or saline after acute systemic injection of a noncompetitive NMDA antagonist, MK-801 (0.1 mg/kg s.c.). RESULTS: A significant attenuation of the MK-801-induced increase in glutamate levels associated with a potentiation of the increase in noradrenaline concentrations was found in the mPFC of MAM-exposed rats, whereas no significant change was observed in the NAcc. MAM-exposed rats also exhibited an exaggerated locomotor hyperactivity, in line with the exacerbation of symptoms reported in schizophrenic patients after administration of noncompetitive NMDA antagonists. CONCLUSIONS: Given the importance of the mPFC in regulating the hyperlocomotor effect of NMDA antagonists, our results suggest that the prefrontal neurochemical alterations induced by MK-801 may sustain the exaggerated locomotor response in MAM-exposed rats. PMID- 17279376 TI - Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality. AB - RATIONALE: Manipulations of the endocannabinoid/fatty acid amide hydrolase (FAAH) signaling systems result in conflicting and paradoxical effects in rodent models of emotional reactivity. OBJECTIVES: In the present study, we tested the hypothesis that the inhibition of FAAH would elicit significant effects in murine models used to screen anxiolytic and antidepressant drugs. MATERIALS AND METHODS: FAAH (-/-) mice and wild-type mice treated with FAAH inhibitors (URB597 and OL 135) were evaluated in standard behavioral screening models for antidepressant (i.e., tail suspension and forced-swim tests) and anxiolytic (i.e., elevated plus maze) agents. The doses of URB597 and OL-135 selected were based on their ability to augment the pharmacological effects (i.e., analgesia, catalepsy, and hypothermia) of exogenously administered anandamide. RESULTS: FAAH (-/-) mice, anandamide-injected FAAH (-/-) mice, or wild-type mice injected with FAAH inhibitors or anandamide failed to exhibit significant effects in standard tests of emotional reactivity, although the antidepressant desipramine and the anxiolytic agent midazolam were active in the appropriate assays. FAAH- (-/-) and URB597-treated mice finally displayed significant effects in the tail suspension test when substantial methodological changes were made (i.e., altered ambient light and increased sample sizes). CONCLUSIONS: Although FAAH suppression can elicit significant effects under some instances in which consequential procedural modifications are made, the present results indicate that the pharmacological inhibition or genetic deletion of FAAH is ineffective in standard mouse models of emotional reactivity. It remains to be established whether the effects of FAAH inhibition in these modified tasks are predictive of their efficacy in treating emotional disorders. PMID- 17279378 TI - Ethical issues in child psychopharmacology research and practice: emphasis on preschoolers. AB - INTRODUCTION: Psychoactive drug prescription for preschoolers has increased over the past decade and has been a controversial topic for those who prescribe, regulate, and research the use of psychotropics in this population. Children and adolescents are deemed vulnerable populations, at risk of being harmed by unethical or suboptimal practice and research and are in need of special protection. Historically, preschoolers have been therapeutic and research "orphans," excluded from pharmacological studies so that the evidence base for their treatment has to be extrapolated from other ages. Within the past few decades, several ethical principles guiding pediatric psychopharmacological research have been developed. The same principles could effectively guide the treatment of these patients. CONCLUSION: Further studies are needed to elucidate the safety and effectiveness of psychotropics, and sound ethical guidelines for their involvement in psychiatric research are needed. This article reviews some challenges facing mental health care providers involved in prescribing or researching the use of psychoactive drugs in preschoolers. Some of these challenges are general to medical treatment and research with children, and others are particular to child psychopharmacological treatment and research. PMID- 17279377 TI - Linking nucleus accumbens dopamine and blood oxygenation. AB - RATIONALE: Animal research suggests that anticipation of reward can elicit dopamine release in the nucleus accumbens (NAcc). Human functional magnetic resonance imaging (FMRI) research further suggests that reward anticipation can increase local blood oxygen level dependent (BOLD) signal in the NAcc. However, the physiological relationship between dopamine release and BOLD signal increases in the NAcc has not yet been established. OBJECTIVES: This review considers pharmacological MRI (phMRI) evidence for a directional relationship between NAcc dopamine release and BOLD signal, as well as implications for human psychopathological symptoms. RESULTS: Accumulating phMRI evidence supports a simple model in which NAcc dopamine release activates postsynaptic D1 receptors, which changes postsynaptic membrane potential, eventually increasing local BOLD signal. This continuing influence can change on a second-to-second basis. CONCLUSIONS: Dopamine release in the NAcc appears to increase local BOLD signal via agonism of postsynaptic D1 receptors. Such a physiological mechanism implies that FMRI may be used to track symptoms related to NAcc dopaminergic dysregulation in psychiatric disorders including schizophrenia and attention deficit/hyperactivity disorder. PMID- 17279379 TI - Auditory grouping occurs prior to intersensory pairing: evidence from temporal ventriloquism. AB - The authors examined how principles of auditory grouping relate to intersensory pairing. Two sounds that normally enhance sensitivity on a visual temporal order judgement task (i.e. temporal ventriloquism) were embedded in a sequence of flanker sounds which either had the same or different frequency (Exp. 1), rhythm (Exp. 2), or location (Exp. 3). In all experiments, we found that temporal ventriloquism only occurred when the two capture sounds differed from the flankers, demonstrating that grouping of the sounds in the auditory stream took priority over intersensory pairing. By combining principles of auditory grouping with intersensory pairing, we demonstrate that capture sounds were, counter intuitively, more effective when their locations differed from that of the lights rather than when they came from the same position as the lights. PMID- 17279380 TI - Preserved dynamic cerebral autoregulation in the middle cerebral artery among persons with migraine. AB - Migraine affects the autonomous nervous system and a recent investigation has also proposed a severe disturbance of dynamic cerebral blood flow regulation in the middle cerebral artery during spontaneous blood pressure oscillations. This study investigates whether dynamic cerebral autoregulation is impaired in persons with migraine among a normal cohort. Out of 94 adults studied to establish normal values for dynamic autoregulation, 19 suffered from migraine according to IHS criteria (10 of them with aura). Transcranial Doppler sonography and fingerplethysmography were used to determine dynamic autoregulation of both middle cerebral arteries following spontaneous low frequency (0.06-0.12 Hz) blood pressure fluctuations (phase and gain of transfer function, correlation coefficient indices Dx and Mx). No significant differences were found for the low frequency variability of blood pressure (power spectral density) and various indices of dynamic cerebral autoregulation between persons with and without migraine. Moreover, no differences were observed between persons with migraine, with and without aura. This study based on a normal cohort does not support the presence of generally impaired cerebral autoregulation dynamics in persons with migraine. Future studies should focus on posterior circulation and particular cerebellar autoregulation. PMID- 17279382 TI - Number magnitude potentiates action judgements. AB - Motor actions can be simulated and generated through the perception of objects and their characteristics. Such functional characteristics of objects with given action capabilities are called affordances. Here we report an interaction between the perception of affordances and the processing of numerical magnitude, and we show that the numerical information calibrates the judgement of action even when no actual action is required. In Experiment 1, participants had to judge whether they would be able to grasp a rod lengthways between their thumb and index finger. The presentation of the rod was preceded by a number or a non-numerical symbol. When a small number preceded the rod, participants overestimated their grasp; conversely, when a large number preceded the rods, they underestimated their grasp. In Experiment 2, participants were requested to judge if two successive rods had the same length, a judgement that did not involve any grasping. The numerical primes had no effect on this judgement, showing that the magnitude/affordance interaction was not due to a simple perceptual effect. Finally, Experiment 3 showed that the interaction was not present with a non numerical ordered sequence, thereby eliminating sequence order as a potentially confounding variable. PMID- 17279381 TI - Prehension synergies: principle of superposition and hierarchical organization in circular object prehension. AB - This study tests the following hypotheses in multi-digit circular object prehension: the principle of superposition (i.e., a complex action can be decomposed into independently controlled sub-actions) and the hierarchical organization (i.e., individual fingers at the lower level are coordinated to generate a desired task-specific outcome of the virtual finger at the higher level). Subjects performed 25 trials while statically holding a circular handle instrumented with five six-component force/moment sensors under seven external torque conditions. We performed a principal component (PC) analysis on forces and moments of the thumb and virtual finger (VF: an imagined finger producing the same mechanical effects of all finger forces and moments combined) to test the applicability of the principle of superposition in a circular object prehension. The synergy indices, measuring synergic actions of the individual finger (IF) moments for the stabilization of the VF moment, were calculated to test the hierarchical organization. Mixed-effect ANOVAs were used to test the dependent variable differences for different external torque conditions and different fingers at the VF and IF levels. The PC analysis showed that the elemental variables were decoupled into two groups: one group related to grasping stability control (normal force control) and the other group associated with rotational equilibrium control (tangential force control), which supports the principle of superposition. The synergy indices were always positive, suggesting error compensations between IF moments for the VF moment stabilization, which confirms the hierarchical organization of multi-digit prehension. PMID- 17279383 TI - Different effects of lesions to auditory core and belt cortex on auditory recognition in dogs. AB - Auditory recognition memory, in contrast to memory in other modalities, is not affected by damage to the perihinal cortex, and its neural basis remains unknown. In an attempt to elucidate this problem, we investigated the role of canine auditory core and belt areas in auditory recognition. Either core or posterior belt areas were surgically removed. The core and belt regions were defined on the basis of response properties and thalamocortical connectivity established in previous studies. The animals were tested on auditory delayed matching to sample (DMS, a recognition memory task) using complex, trial-unique auditory stimuli. Both core and belt lesions impaired auditory recognition, however, the underlying deficit was different. Lesions to the core areas impaired auditory localization abilities. Lesions to the posterior belt areas did not affect this component of the recognition task, but affected auditory quality discrimination and/or recognition. The deficit following the posterior belt lesion did not increase with retention delay, suggesting that auditory belt areas do not constitute a substrate for auditory recognition memory. Their main function appears to be processing of complex sound patterns, including immediate recognition. PMID- 17279384 TI - Control of upright stance over inclined surfaces. AB - The present work investigated the control of upright posture on inclined surfaces (14 degrees). Such conditions could, for example, change the contributions of muscle spindles resulting in alterations in postural sway. Subjects stood in quiet stance over a force platform positioned in one of three different fixed positions: horizontal (H), toes-up (ankle dorsi-flexion, D) and toes-down (ankle plantar-flexion, P). The experiments were done in the presence and also in the absence of vision. The analysis of the resulting sway was based on the power spectrum of the center of pressure displacement in the anterior-posterior direction (CP_ap). Analysis of the electromyogram (EMG) of the leg muscles and evaluation of the level of presynaptic inhibition (PSI) of the soleus (SO) Ia afferents complemented the study. The results showed that the spectrum of the CP_ap changed with the inclination of the surface of support. In condition D a higher instability was found as reflected by the higher spectral amplitudes at lower frequencies (below 0.3 Hz). On the other hand, the CP_ap of subjects in condition P contained increased amplitudes at high frequencies (above 0.3 Hz) and smaller amplitudes at low frequencies. The modifications found in the CP_ap power spectra when standing over an inclined surface may indicate changes in both short term and long-term systems of postural control. These results do not seem to be associated with changes in group Ia feedback gain since no changes in the level of PSI were found among the three standing conditions. The SO EMG increased in condition P but did not change in condition D. On the other hand, the tibialis anterior had a tendency towards increased bursting activity in condition D. Eye closure caused an increase in the power of the oscillations at all spectral frequencies in the three standing conditions (H, P or D) and also a change in the profile of the CP_ap power spectrum. This may suggest a nonlinearity in the postural control system. The control of the slow component of the postural sway was more dependent on vision when the subject was in condition D, probably in association with the biomechanical constraints of standing on a toes-up ramp. A conclusion of this work was that, depending on the postural demand (direction of the ramp of support), the ensuing proprioceptive and biomechanical changes affect differentially the fast and slow mechanisms of balance control. PMID- 17279385 TI - Aging affects the predictive control of grip force during object manipulation. AB - We examined the effects of aging on the predictive control of grip force during object manipulation under various external force fields. Participants rhythmically moved a hand-held object (m = 0.4 kg) in the horizontal plane under three experimental conditions: (1) with an elastic cord attached to the upper arm (ARM), (2) with the elastic cord attached to the object (OBJECT), and (3) without any elastic cord (NO ELAST). Performance was evaluated in terms of both metric and spectral characteristics of the grip force (GF) profile, in relation to the movement-induced variations in load at the object-finger interface (LFO). The performance of a group of 12 older adults (mean age = 66.3 years) was compared to the performance of a group of 12 young adults (mean age = 25.0 years), whose metric characteristics were reported earlier (Exp. Brain Res. 172:331, 2006). Although elderly participants exerted a larger mean GF, a tight linear coupling between GF and LFO was found for both groups in OBJECT. In ARM and NO ELAST, coefficients of cross-correlations were markedly lower, the more so for the elderly participants. Adjustments in GF occurred slightly in advance of variations in LFO in young adults (+7 ms) and somewhat delayed in the elderly ( 26 ms). Spectral analyses revealed that in OBJECT, LFO and GF varied primarily at the frequency of movement. In ARM and NO ELAST, where LFO varied at twice this frequency, GF modulations contained a substantial frequency component at the frequency of movement, with this effect being more pronounced for the elderly participants. We conclude that both young and older adults demonstrate a predictive control of GF, capable of separating external force fields acting on the arm or on object-finger interface. However, in the presence of variations in LFO occurring at twice the frequency of movement, the spectral profile of GF exhibits a non-functional component of variation at the frequency of movement. Aging amplifies this latter effect, thereby affecting the efficiency of the predictive control of grip force. PMID- 17279386 TI - Intact encoding, impaired consolidation in procedural learning in Parkinson's disease. AB - Idiopathic Parkinson's disease (IPD) patients and matched healthy participants were compared on a non-motor procedural task involving semantically related inverted word pairs, and 3 months later to determine the extent of skill consolidation. IPD patients were found to acquire new procedural skills necessary to read these inverted words, thus indicating that they are not impaired in all types of procedural learning. However, results on post-tests 3 months later, revealed significant group differences with IPD subjects showing little off-line learning relative to the controls. This suggests that a dopamine (DA) deafferented neural system is not consolidated in the same way that a normally DA innervated system is, and that impaired maintenance of procedures and routines may place IPD patients in a situation of constant relearning of embedded strategies in motor and non-motor domains. PMID- 17279387 TI - Molecular and conventional responses of large rainbow trout to dietary phosphorus restriction. AB - The dietary phosphorus (P) requirement for large fish is difficult to estimate because of insensitivities of known P status indicators. We examined dietary P requirement of large rainbow trout (mean body weight 278 g) using recently identified P-responsive genes (mRNA abundances) as well as conventional serum P and bone P. Fish were fed six diets (varied P contents), and the tissues of intestine, pyloric caeca (PC), kidney, serum and bone were collected at varying time intervals. Serum P responded clearly to dietary P by day 2, but the estimated P requirement based on this variable changed as feeding duration continued. Bone P did not respond clearly until week 7. Among P-responsive genes studied, Na/Pi cotransporter in PC (PC-NaPi) was the most sensitive, and responded in 2 days. Fish-to-fish (within treatment) variance was larger in mRNA than in serum P and bone P levels. Estimated dietary P requirements (%P in dry diet) were 0.45 (based on serum P), 0.45 (based on bone P), 0.36 (based on PC NaPi), 0.33 (based on intestinal NaPi), 0.71 (based on renal NaPi), and 0.33 (based on mitochondrial Pi carrier). This study is the first to evaluate the potential of genomic approaches in determining nutrient requirements of fish. PMID- 17279388 TI - Thermal sensitivity of metabolic rates and swimming performance in two latitudinally separated populations of cod, Gadus morhua L. AB - Atlantic cod populations live in a wide thermal range and can differ genetically and physiologically. Thermal sensitivity of metabolic capacity and swimming performance may vary along a latitudinal gradient, to facilitate performance in distinct thermal environments. To evaluate this hypothesis, we compared the thermal sensitivity of performance in two cod stocks from the Northwest Atlantic that differ in their thermal experience: Gulf of St Lawrence (GSL) and Bay of Fundy (BF). We first compared the metabolic, physiological and swimming performance after short-term thermal change to that at the acclimation temperature (7 degrees C) for one stock (GSL), before comparing the performance of the two stocks after short-term thermal change. For cod from GSL, standard metabolism (SMR) increased with temperature, while active metabolism (AMR, measured in the critical swimming tests), EMR (metabolic rate after an exhaustive chase protocol), aerobic scope (AS) and critical swimming speeds (U (crit) and U (b-c)) were lower at 3 degrees C than 7 or 11 degrees C. In contrast, anaerobic swimming (sprint and burst-coasts in U (crit) test) was lower at 11 than 7 or 3 degrees C. Factorial AS (AMR SMR(-1)) decreased as temperature rose. Time to exhaustion (chase protocol) was not influenced by temperature. The two stocks differed little in the thermal sensitivities of metabolism or swimming. GSL cod had a higher SMR than BF cod despite similar AMR and AS. This led factorial AS to be significantly higher for the southern stock. Despite these metabolic differences, cod from the two stocks did not differ in their U (crit) speeds. BF cod were better sprinters at both temperatures. Cod from GSL had a lower aerobic cost of swimming at intermediate speeds than those from BF, particularly at low temperature. Only the activity of cytochrome C oxidase (CCO) in white muscle differed between stocks. No enzymatic correlates were found for swimming capacities, but oxygen consumption was best correlated with CCO activity in the ventricle for both stocks. Overall, the stocks differed in their cost of maintenance, cost of transport and sprint capacity, while maintaining comparable thermal sensitivities. PMID- 17279389 TI - Mechanisms of dietary Cu uptake in freshwater rainbow trout: evidence for Na assisted Cu transport and a specific metal carrier in the intestine. AB - Copper (Cu) is both a vital nutrient and a potent toxicant. The objective of this study was to analyze the mechanistic nature of intestinal Cu transport in rainbow trout using radiolabeled Cu (64Cu) and an in vitro gut sac technique. Reduction of mucosal NaCl levels inhibited Cu transport while increase caused stimulation; Na(2)SO(4) had an identical effect, implicating Na(+) rather than the anion. These responses were unrelated to solvent drag, osmotic pressure or changes in transepithelial potential. The presence of elevated luminal Ag stimulated Cu and Na(+) uptake. Phenamil caused a partial inhibition of both Cu and Na(+) uptake while hypercapnia stimulated Na(+) and Cu transport. Cu uptake was sensitive to luminal pH and inhibited by a tenfold excess of Fe and Zn. These factors had no effect on Na(+ )uptake. On the basis of these results we propose a novel Na(+) assisted mechanism of Cu uptake wherein the Na(+) gradient stimulates an increase in the H(+) concentration of the brushborder creating a suitable microenvironment for the effective transport of Cu via either DMT1 or Ctr1. PMID- 17279390 TI - A review of feeding and nutrition of herbivorous land crabs: adaptations to low quality plant diets. AB - This paper reviews the nutritional ecology, the digestive physiology, and biochemistry of herbivorous land crabs and the adaptations that they possess towards a diet of plant material. Land crab species that breathe air and forage out of water can be divided into three feeding specialisations: primarily carnivorous, deposit feeders feeding on micro-organisms and organic matter in the sediment, and herbivores consuming mainly plant material and its detritus. The last forms the focus of this review. The diets of the herbivores are low in nitrogen and high in carbon, are difficult to digest since they contain cellulose and hemicellulose, and may disrupt digestion due to the presence of tannins. Herbivorous crustaceans are able to efficiently utilise plant material as their primary nutrient source and are indeed able to meet their nitrogen requirements from it. Herbivorous land crabs display a range of adaptations towards a low nitrogen intake and these are discussed in this review. They also appear to endogenously produce cellulase and hemicellulase enzymes for the digestion of cellulose and hemicellulose. Generalised and specific adaptations allow them to inhibit the potentially negative digestive effects of tannins. To digest plant material, they possess a plastic digestive strategy of high food intake, short retention time, high assimilation of cell contents, and substantial digestion of cellulose and hemicellulose. PMID- 17279391 TI - Overproduction and characterization of a recombinant D-amino acid oxidase from Arthrobacter protophormiae. AB - A screening of soil samples for D-amino acid oxidase (D-AAO) activity led to the isolation and identification of the gram-positive bacterium Arthrobacter protophormiae. After purification of the wild-type D-AAO, the gene sequence was determined and designated dao. An alignment of the deduced primary structure with eukaryotic D-AAOs and D-aspartate oxidases showed that the D-AAO from A. protophormiae contains five of six conserved regions; the C-terminal type 1 peroxisomal targeting signal that is typical for D-AAOs from eukaryotic origin is missing. The dao gene was cloned and expressed in Escherichia coli. The purified recombinant D-AAO had a specific activity of 180 U mg protein(-1) for D methionine and was slightly inhibited in the presence of L-methionine. Mainly, basic and hydrophobic D-amino acids were oxidized by the strictly enantioselective enzyme. After a high cell density fermentation, 2.29 x 10(6) U of D-AAO were obtained from 15 l of fermentation broth. PMID- 17279392 TI - Prokaryotic and eukaryotic features observed on the secondary structures of Giardia SSU rRNAs and its phylogenetic implications. AB - Phylogenetic position of a diplomonad protist Giardia, a principle cause of diarrhea, among eukaryotes has been vigorously debated so far. Through the comparisons of primary and secondary structures of SSU rRNAs of G. intestinalis, G. microti, G. ardeae, and G. muris, I found two major indel regions (a 6-nt indel and a 22-26-nt indel), which correspond to the helix 10 of the V2 region and helices E23-8 to E23-9 of the V4 region, respectively. As generally shown in eukaryotes, G. intestinalis and G. microti have commonly a relatively longer helix 10 (a 7-bp stem and a 4-nt loop), and also the eukaryote-specific helices E23-6 to E23-9. On the other hand, G. muris and G. ardeae have a shorter helix 10: a 2-bp stem and a 6-nt loop in G. ardeae and a 3-bp stem and a 6-nt loop in G. muris. In the V4, they have a single long helix (like the P23-1 helix in prokaryotes) instead of the helices E23-6 to E23-9. Among the four Giardia species, co-appearance of prokaryote- and eukaryote-typical features might be significant evidence to suggest that Giardia (Archezoa) is a living fossil showing an "intermediate stage" during the evolution from prokaryotes to eukaryotes. PMID- 17279394 TI - Discrimination of Cryptosporidium species by denaturing gradient gel electrophoresis. AB - Denaturing gradient gel electrophoresis (DGGE) was used for the discrimination of three species and one genotype of the protozoan parasite Cryptosporidium: the C. parvum, C. andersoni, C. muris, and C. muris Japanese field mouse genotype. A set of primers specific for the 18S rRNA gene of Cryptosporidium was used in the DGGE; consequently, the four strains showed different banding patterns. This is a potentially convenient and precise method for the discrimination of Cryptosporidium spp. PMID- 17279393 TI - The use of echinostomes to study host-parasite relationships between larval trematodes and invertebrate and cold-blooded vertebrate hosts. AB - Echinostomes are intestinal trematodes with life cycles that are easy and inexpensive to maintain in the laboratory. For this reason, echinostomes have served for years as experimental models in different areas of parasitology. However, the usefulness of these trematodes in experimental parasitology has been under estimated. In this paper, we discuss the life cycles of echinostomes and the techniques used to maintain them in the laboratory. We further examine the characteristics of these trematodes that make them useful models for the analysis of larval parasite-host relationships. Echinostomes are useful for studies on the immunobiology of snails, host-finding processes of free-living larval stages, effects of larval trematode infections on anuran populations, and studies on analytes in the larval trematodes and their snail intermediate hosts. PMID- 17279395 TI - Analysis of the 5.8S rRNA and internal transcribed spacers regions of the variant Naegleria fowleri Thai strain. AB - The aim of this study was to analyze the internal transcribed spacers regions (ITS) of the of 5.8S ribosomal RNA (rRNA) gene of four isolants of Naegleria fowleri. Three of four Thai strains were isolated from patients and one from the environment. All four strains were confirmed to be N. fowleri by species-specific PCR using DNA extracted using a QIAamp DNA mini kit. The ITS lengths observed were ITS1, 85 bp; ITS2, 106 bp; and 5.8S, 176 bp. Five discriminating deca nucleotide primers A1, A15, B10, B12, and B15 were used in this study. Specific prominent bands were observed after PCR with each primer: 600 bp with A1; 615 bp with A15; 1,580 bp with B10; 930 and 510 bp with B12; and 310 bp with B15. All sequences were compared with the Japanese J16-1-42E sequence in the Genbank database. After alignment, our sequences contained only 0.5% variation from the J16-1-42 sequence. The ITS main products of the strain from the environment were similar to those of the three strains from Thai patients. The four Thai strains have essentially the same 5.8S rRNA genes as Cattenom Japanese J16(1) 42E strain. PMID- 17279396 TI - Mixture design as a first step for optimization of fermentation medium for cutinase production from Colletotrichum lindemuthianum. AB - Cutinase enzymes from fungi have found diverse applications in industry. However, most of the available literature on cutinase production is related to the cultivation of genetically engineered bacteria or yeast cells. In the present study, we use mixture design experiments to evaluate the influence of six nutrient elements on production of cutinase from the fungus Colletotrichum lindemuthianum. The nutritional elements were starch, glucose, ammonium sulfate, yeast extract, magnesium sulfate, and potassium phosphate. In the experimental design, we imposed the constraints that exactly one factor must be omitted in each set of experiments and no factor can account for more than one third of the mixture. Thirty different sets of experiments were designed. Results obtained showed that while starch is found to have negative influence on the production of the enzyme, yeast extract and potassium phosphate have a strong positive influence. Magnesium sulfate, ammonium sulfate, and glucose have low positive influence on the enzyme production. Contour plots have also been created to obtain information concerning the interaction effects of the media components on enzyme production. PMID- 17279397 TI - Special issue on biopacemaking: clinically attractive, scientifically a challenge. PMID- 17279399 TI - [Anxiety disorders. Causes, clinical picture and treatment]. AB - Anxiety disorders are among the most frequent mental disorders together with affective disorders with a lifetime prevalence of 18%. The pathogenesis of these disorders is complex and includes biological and psychosocial factors. Modern diagnostic classification systems (ICD-10, DSM-IV) differentiate between panic disorder with or without agoraphobia, generalized anxiety disorder, social phobia and specific phobia. Recommended treatment approaches include psychotherapy as well as pharmacotherapy, which have to be preceded by an empathic psychoeducation. Today, cognitive behavioural psychotherapy and modern antidepressants such as selective serotonin reuptake inhibitors represent the first-line therapy of most anxiety disorders. This review gives an overview of pathogenesis, clinical presentation and current treatment standards. PMID- 17279398 TI - [Executive functions in patients with depression. The role of prefrontal activation]. AB - Depression is a multifarious disease, having an impact on most aspects of everyday life. Cognitive deficits cause considerable impairments and restraints in performance and have become one of the major clinical and research foci in recent years. According to previous work, deficits in executive functioning seem to be particularly prominent. At present only a few functional neuroimaging studies investigated the neurofunctional correlates aimed at these deficits by using specific activation tasks. These findings are somewhat controversial, revealing prefrontal hypo- as well as hyperactivation as a substrate of executive performance. This paper reviews current functional neuroimaging findings within a framework of depression as a dysfunction in limbic-cortical circuits. As a conclusion, the concept of "simple" hypofrontality does not offer a satisfactory explanation. Rather, a more dynamic model will be necessary in order to achieve a more realistic concept of executive deficits in depression. PMID- 17279401 TI - Imaging features of clear-cell ependymoma of the spinal cord. AB - A 10-year-old girl presented with increasing lower back pain without gait or sphincter disturbances. MRI demonstrated a large, intramedullary tumor at the level of the conus. The imaging findings were unlike those of a classic ependymoma or astrocytoma. Histopathologic examination demonstrated clear-cell ependymoma, which is a distinct entity. We found three cases of clear-cell ependymoma of the spinal cord reported in the literature. Clear-cell ependymoma of the spinal cord can be resected completely and needs to be recognized for its imaging features, benign course and favorable prognosis. PMID- 17279400 TI - Contrast-enhanced magnetic resonance angiography for the detection of crossing renal vessels in children with symptomatic ureteropelvic junction obstruction: comparison with operative findings. AB - BACKGROUND: Crossing renal vessels (CRV) are associated with ureteropelvic junction (UPJ) obstruction, particularly when presentation is beyond the neonatal period. Their presence may influence surgical management. OBJECTIVE: To evaluate the accuracy of contrast-enhanced magnetic resonance angiography (CE-MRA) in the identification of CRV in children requiring surgical treatment of symptomatic UPJ obstruction, against a gold standard of laparoscopic or open surgical findings. MATERIALS AND METHODS: We reviewed CE-MRA studies (3-D T2-weighted turbo spin echo and multiphase 3-D spoiled gradient echo following intravenous gadolinium administration) of 14 children, age range 6-15 years, performed prior to surgery for suspected CRV-related UPJ obstruction. Consensus reviews of the CE-MRA studies were compared with surgical findings. RESULTS: CE-MRA demonstrated CRV at the level of the obstruction in nine and no crossing vessels in five children. These were all verified intraoperatively (chi2=14.0; P<0.001). In eight of the nine patients with CRV there was no evidence of intrinsic obstruction at surgery. In the remaining patient there was fibrosis of the upper ureter. CONCLUSION: CE MRA is an accurate means of identifying CRV in children older than 6 years with symptomatic UPJ obstruction. PMID- 17279402 TI - CT of the chest in the evaluation of idiopathic pulmonary arterial hypertension in children. AB - BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease in children. By definition it is a diagnosis of exclusion, and CT of the chest is primarily performed to exclude other causes. Previous studies have defined CT features suggestive of the diagnosis of IPAH, but these have all been limited to the adult population. OBJECTIVE: Contrast-enhanced chest CT and high-resolution CT findings in IPAH were evaluated in an attempt to define features consistently seen in children with this condition. MATERIALS AND METHODS: The chest CT scans performed at initial presentation were reviewed in 17 children with echocardiographic or angiographic evidence of IPAH. RESULT: There were nine boys and eight girls, ranging in age from 1 month to 17 years. The extrapulmonary findings included cardiomegaly with right-sided cardiac enlargement, which was seen in 13 children. The central pulmonary arteries were enlarged in 15 children, with peripheral enlargement in two. In six children this resulted in bronchial compression. In addition, mediastinal and hilar lymphadenopathy was noted in three children. Prominent intrapulmonary features included a peripheral vasculopathy, with enlarged tortuous vessels, seen in eight children. Ill-defined ground-glass centrilobular opacities were also noted in eight children, representing the most common parenchymal abnormality. Other findings included septal lines in five, diffuse ground-glass opacification in four and focal hyperlucent zones in three. Mosaic attenuation was seen in one child. CONCLUSION: A variety of imaging findings are identified in IPAH. Features particularly consistent with the diagnosis include peripheral vasculopathy and centrilobular opacities in the setting of cardiomegaly and central pulmonary arterial enlargement. PMID- 17279403 TI - Patient access to pharmaceuticals: an international comparison. AB - We have identified eight sub-dimensions of patient access to pharmaceuticals: marketing approvals, time of marketing approval, coverage, cost sharing, conditions of reimbursement, speed from marketing approval to reimbursement, extent to which beneficiaries control choice of their drug benefit, and evenness of the availability of drugs to the population. For a sample of commonly used best-selling drugs in the United States (US), we measured these eight access sub dimensions across four health systems: France, the Netherlands, the United Kingdom (UK), and the US. Although the US approved between 15 and 18% more drugs than the other three countries, the US was slower than France and the UK to approve drugs licensed in all four countries. The percentage of drugs covered is approximately the same for all four countries. For covered drugs, we observe the least cost sharing by patients in the Netherlands. The Netherlands imposes conditions of reimbursement on a much larger percentage of drugs. France seems to be the slowest in respect of speed from marketing approval to reimbursement. The US is the most flexible in terms of the extent to which beneficiaries control their choice of drug benefit but it is the least universal in terms of evenness of the availability of drugs to the population. Our study confirms the frequently cited problems of access in European countries: lag between marketing approval and reimbursement, and inflexibility in respect of the extent to which beneficiaries control their choice of drug benefit. At the same time, our study confirms, qualitatively, different kinds of access problems in the US: relatively high patient cost sharing for pharmaceuticals, and wide variation in coverage. PMID- 17279405 TI - [Gastrointestinal motility disorders. Interdisciplinary presentation of a complex disease spectrum]. PMID- 17279404 TI - Variations in activity and practice patterns: a French study for GPs. AB - OBJECTIVES: To identify the different practice profiles of general practitioners (GPs) in order to test the hypothesis of heterogeneity in physician behaviour. DATA: For the year 2000, 4,660 GPs from two regions in France. VARIABLES: volume and structure of the physicians' medical activity, income level, personal characteristics, socioeconomic and geographical environment, characteristics of their patients. METHODS: A cluster analysis to identify different practice profiles and a regression analysis to display the determinants of the physicians' activity. RESULTS: Four different homogeneous groups can be identified, each one associating a physician's level of activity to his socioeconomic status. The level and the intensity of medical activity depend on individual factors, patients' characteristics as well as the socioeconomic context. CONCLUSIONS: There is no uniformity in the way GPs practice medicine. An immediate consequence is that any cost-containment measure that is applied uniformly to all GPs inevitably results in different outcomes according to the physicians' category type. PMID- 17279406 TI - [Leiomyomatosis of the colon: case report and literature review]. AB - We present the findings of a 67 year old male patient with an intestinal leiomyomatosis localized in the rectum. To our knowledge, this is the fifth case of intestinal leiomyomatosis reported so far. The most characteristic findings of this rare disease include a cuff-like tumorous proliferation of smooth muscle within the bowel wall which may extend into extramural tissue and result in a stenosis of a longer bowel segment. Because of severe obstructive symptoms over 5 years, the patient had to undergo surgery with resection of the rectum. The histological examination revealed a morphology and immunophenotype comparable to usual leiomyomas with the exception of hyalinosis-like changes in the blood vessels, apparently a special feature of leiomyomatosis. A novel finding in our case was the occurrence of skeinoid fibers which have so far only been reported in gastrointestinal stromal tumors. PMID- 17279407 TI - [Molecular biology, basic research and diagnosis of Hirschsprung's disease]. AB - The proto-oncogene RET is the major gene responsible for Hirschsprung's disease (HSCR), with RET mutations also implied in different pathologies. A variety of mutations of the RET proto-oncogene have been detected in HSCR patients. Special attention should be paid to rare patients who carry mutations of one of the critical cysteine residues of these exons, known to predispose to MEN2A. In these cases, HSCR can be associated with the development of neuroendocrine tumors such as medullary thyroid carcinoma (MTC) or MEN2A, for which a prophylactic thyroidectomy is advisable in the presence of a tumor causing RET mutation. In combined MEN2A/HSCR families, RET gene testing, tumor screening and prophylactic thyroidectomy are indicated as in MEN2A. The multigenic origin of HSCR and the absence of a "standard" RET mutation associated with HSCR currently make a routine molecular diagnosis impossible. PMID- 17279408 TI - [The morphological characteristics of aplastic and atrophic desmosis of the intestine]. AB - In addition to the enteric nervous system, the interstitial cells of Cajal and the smooth musculature, the collagenous fibre network of the muscularis propria plays a major role in the coordination of peristalsis. Partial or complete absence of this network in patients with chronic constipation has been described as 'desmosis'. Two major subtypes of desmosis can be distinguished: in the rare congenital (primary) aplastic desmosis of childhood, the collagenous fibre network is not formed. This is characteristic of microcolon megacystis syndrome and is associated with aperistalsis. The more common atrophic (secondary) desmosis of adulthood is typically incomplete and associated with a hypoperistaltic syndrome. Neither the etiology nor the pathogenesis of desmosis are currently understood. Atrophic desmosis may occur after previous inflammatory episodes. Further extensive studies are needed to better understand the pathogenesis, etiology and functional implications of this disease. PMID- 17279409 TI - [Conventional histological diagnostics in coloproctology]. AB - With the introduction of immunohistochemical methods, histopathological diagnosis based on formalin fixed, paraffin embedded tissue in coloproctology has substantially improved. In recent years, the routine use of immunohistochemistry for S100, cathepsin D and a picrosirius red staining has proven to be sufficient for the diagnosis of hypoganglionosis of the myenteric plexus and desmosis of the muscularis propria. In some cases, an immunohistochemical reaction for CD 117 is also necessary for the evaluation of Cajal cells. In contrast, in ultrashort Hirschsprung's disease, aganglionosis of the anal ring, aganglionosis of the musculus corrugator cutis ani, and internal sphincter, the histochemical acetylcholinesterase reaction is essential and not replaceable by any immunohistochemical method.Immunohistochemistry, classical histological stains and enzyme histochemistry are complementary histopathological techniques. In contrast to immunohistochemistry, enzyme histochemistry requires native cryostat sections for the assessment of enzyme activity. As a consequence, biopsy performance and transport to pathology departments should be particularly well organized. PMID- 17279410 TI - [Intestinal neuronal dysplasia type B: how do we understand it today?]. AB - Intestinal neuronal dysplasia type B (IND B) is currently considered to be a subtle malformation of the submucosal plexus, leading to an increased proportion of over-sized ganglia and potentially accompanied by a mild, chronic gastrointestinal motility disturbance. The diagnosis of IND B is morphologically based and involves the demonstration of an increased proportion of giant ganglia in the submucous plexus related to the patient's age. Giant ganglia are physiologically frequent in the neonatal period. Therefore, IND B should not be diagnosed prior to 1 year of age. Morphological features of IND B may occur as an isolated finding or may be observed proximal to an aganglionic segment. IND B and constipation may resolve spontaneously up to the age of 4 years. Treatment of IND B is usually conservative, surgical resection is currently deemed necessary only in a minority of patients. The pathogenesis of IND B is still incompletely understood and the etiology unknown. Future research on the basis of standardized diagnostic conditions is expected to result in a better understanding of this disease, and to reveal the cause of aberrant ganglion development. PMID- 17279412 TI - Reciprocal effects of Th1 and Treg cell inducing pathogen-associated immunomodulatory molecules on anti-tumor immunity. AB - We have addressed the hypothesis that pathogen-associated immunomodulatory molecules may influence anti-tumor immunity through their pro- and anti inflammatory activities and abilities to induce effector and regulatory T (Treg) cells. We found that CpG oligonucleotides (CpG) and cholera toxin (CT), which promote Th1 or Th2/Treg cell biased responses, respectively, had differential effects on tumor growth. Therapeutic peritumoral administration of CpG significantly reduced subcutaneous tumor growth and prolonged survival, whereas CT enhanced tumor growth and reduced survival. Peritumoral administration of CpG enhanced the frequency of IFN-gamma-secreting and reduced IL-10-secreting CD4(+) and CD8(+) T cells, in the tumor and in the draining lymph nodes, whereas, CT significantly enhanced the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells, but reduced IFN-gamma-secreting T cells infiltrating the tumor. In contrast to the beneficial effect of CpG in mice with subcutaneous tumors, CpG or CT had no protective effect against tumor growth in the lungs when given therapeutically by the nasal route. However, prophylactic intranasal administration of CpG significantly reduced the number of lung metastases and this was associated with an enhanced frequency of IFN-gamma-secreting CD8(+) T cells in the draining lymph node and enhanced tumor-specific CTL responses. Our findings demonstrate that pathogen-associated molecules can either inhibit or enhance anti-tumor immunity by selectively promoting the induction of effector or regulatory T cells, and that the environment of the growing tumor influences the protective effect. PMID- 17279411 TI - Reconstruction of bone defects with impacted allograft in femoral stem revision surgery. AB - A retrospective clinical review was done on 54 revision hip patients. Radiological analysis examined the Gross and AAOS classifications, stem position, cement mantles, allograft and evolution (subsidence, resorption and remodelling). The Harris Hip score was used for clinical assessment. We used bone bank allograft and a polished non-collared stem LD. The follow-up period was 60.5 months (19.4-152.4), and the average age 68.5 (range: 22-85). There were 21 females and 33 males. The surgical approach was: lateral (5.56%) posterior (91.4%); trochanteric osteotomy: 25.9%; associated acetabular revision: 59.3%; previous operations: 1.9. The preoperative Harris score was 35 (28-40) and rose to 81 (50-99) postoperatively. The stem alignment was neutral (44.44%), varus (38.89%) and valgus (16.67%). The femur/stem diameter relationship was 1.8 (1.2 2.7). There were no changes in stem alignment in 94.4%. An adequate cement mantle was: proximal zone (61.1%), medium zone (27.8%) and distal zone (16.7%). The rate of any subsidence was 38.9% (progressive: 12.96%). The rate of complications was 40.7% and included periprosthetic fracture: 14.8%; superficial infection: 1.9%; deep late infection: 1.9%; dislocation: 3.7%; heterotopic ossification: 13%. The rate of new stem revision was 16.6%. The clinical and radiological success rate was 77.78%. A greater incidence of revisions has been found in stem malalignment, progressive subsidence, a Harris increase of <20 points, allograft resorption, small diameter stems and inadequate cement mantle. We recommend hard impaction and a cement mantle of at least 2 mm. Non-progressive subsidence does not increase stem loosening. The technique has been useful in recovering bone stock in a severely defective femur and achieves a stable reconstruction. The level of evidence was therapeutic study level III-2 (retrospective cohort study; see the instructions to the authors for a complete description of the levels of evidence). PMID- 17279413 TI - Density of DC-LAMP(+) mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. AB - As the most potent antigen presenting cells, dendritic cells (DCs) play key roles in the immune response against tumors. Their density in the tumor tissue has been associated with prognosis in patients with various cancers. However, few studies have been aimed at the presence and maturation state of DCs in cutaneous melanoma, with regard to their potential clinical correlates. In this study, the density of DCs expressing CD1a and the maturation marker DC-LAMP was determined by immunohistochemistry in primary tumor samples from 82 patients with cutaneous malignant melanoma. Intratumoral and peritumoral cell densities were analyzed in relation to tumor thickness and the subsequent development of metastases, as well as to patients' survival. CD1a(+) DCs were found both infiltrating melanoma cell nests and in the surrounding stroma, while DC-LAMP(+) mature DCs were generally confined to the peritumoral areas, associated with lymphocytic infiltrates. DC density values significantly correlated with the number of activated (CD25(+) or OX40(+)) T lymphocytes (p < 0.001). The degree of infiltration by CD1a(+) and DC LAMP(+) DCs showed strong inverse correlation with the thickness of melanomas (p < 0.001). High peritumoral density of mature DCs was associated with significantly longer survival (p = 0.0195), while density of CD1a(+) cells had a prognostic impact of borderline significance (p = 0.0610). Moreover, combination of high peritumoral CD1a(+) or DC-LAMP(+) cell density with high number of CD25(+) or OX40(+) lymphocytes identified patient subgroups with more favorable survival compared to other subgroups. A multivariate survival analysis involving DC and activated T-cell densities alone and in combinations, as well as traditional prognostic factors, identified high DC-LAMP(+) cell/high OX40(+) cell density and Breslow index as independent predictors of good prognosis. These results suggest that the presence of CD1a(+) DCs primarily depends on the thickness of melanomas, without direct relationship with the patients' survival. On the other hand, the density of mature DCs, especially in association with that of activated T cells, proved of prognostic importance, suggesting that these parameters could be considered as signs of a functional immune response associated with better outcome of the disease. PMID- 17279414 TI - Reviewer's comment concerning MS-no: ESJ-06-0340.R1 entitled "Asymmetric evolution of anterior chest wall blood supply in female adolescents with progressive right-convex thoracic idiopathic scoliosis" by P. Iliopoulos et al. PMID- 17279415 TI - Early clinical impact of iron overload in stem cell transplantation. A prospective study. AB - Toxic-infectious complications may be related with iron toxicity after a stem cell transplant (SCT). Eighty one patients who underwent SCT were prospectively evaluated over 3 months for mucositis, bacteraemia and febrile days. Pre-SCT transferrin saturation (TS), ferritin level and the number of days with TS >or= 80% after transplant were determined. A ferritin level >1,500 microg/l predicted the appearance of severe mucositis, bacteraemia and days with fever in univariate (P = 0.03, P = 0.03 and P = 0.03) and multivariate analysis (P = 0.03, P = 0.006 and P = 0.002). Nevertheless, further statistical studies revealed that the predictive value of pre-SCT ferritin levels was restricted to AUTO-transplanted patients in both univariate (P = 0.05, P = 0.05 and P < 0.001) and multivariate (P = 0.03, P = 0.05 and P < 0.001) analysis, in contrast with the ALLO transplanted group where this variable did not reach statistical significance. In conclusion, iron burden seems to influence the appearance of toxic-infectious complications during the first 3 months after transplant in AUTO-transplanted patients. PMID- 17279416 TI - Incidence of the HFE gene mutations in a cohort of non-Spanish origin neonates in Madrid. PMID- 17279417 TI - Transforming growth factor-beta downregulates interleukin-2-induced phosphorylation of signal transducer and activator of transcription 5 in human renal cell carcinoma. AB - PURPOSE: We investigated signal transducer and activator of transcription-5 (STAT5) activation status in renal cell carcinoma (RCC) and the role of transforming growth factor-beta (TGF-beta) in the process. METHODS: Twenty normal and RCC tissues were obtained from radical nephrectomy specimens for the assessment of expressions of phosphorylated STAT5 (p-STAT5) and TGF-beta1 (Western blot) and for localization and assessment of their relationship (immunohistochemical and immunofluorescence stains). By using four RCC cell lines and four primary cultured cells, the effect of TGF-beta1 and/or interleukin-2 (IL 2) on the expressions of p-STAT5 were analyzed. RESULTS: In RCC samples, expression of p-STAT5 was significantly reduced while expression of TGF-beta was enhanced compared with normal kidney tissues (P < 0.001 and P = 0.003, respectively). P-STAT5 was observed almost exclusively in the nuclei of normal kidney tissues while TGF-beta was identified in the cytoplasm of cells of both tissues reflecting the Western results. In both RCC cell lines and cells from primary cultures, treatment with TGF-beta or antibody did not significantly alter STAT5 activation. However, TGF-beta significantly suppressed IL-2-induced STAT5 activation, whereas anti-TGF-beta antibodies enhanced IL-2-induced STAT5 further. CONCLUSIONS: STAT5 activation is suppressed in RCC compared with normal renal parenchyma. It may be attributed to the RCC-derived TGF-beta which also interferes with IL-2-induced STAT5 pathway activation. PMID- 17279418 TI - [Treatment of chronic tube dysfunction. Use of the tube conductor]. AB - BACKGROUND: Chronic tube dysfunction plays a major part in the development of chronic otitis media. Owing to the complex structure of the Eustachian tube, the development of successful therapeutic approaches to the treatment of tube function disorders is still difficult even today. The application of a gold tube wire (tube conductor) was reported in 1991, but no studies have yet been performed on the postoperative success rates achieved with tube conductors. MATERIAL AND METHODS: In a retrospective study, the data relating to 125 patients who were operated on from 1996 to 1999 for treatment of different forms of chronic otitis media and also underwent transtympanic tube conductor implantation to improve tube ventilation disorder were evaluated. Data on pre- and postoperative tube function were available for 96 patients after a mean follow-up period of 18 months. RESULTS: All tube implantations were achieved without complications. Tube function normalized in 8 patients (8.3%), while the tube ventilation disorder remained unaffected in 88 patients (91.7%). A total of 23 (18.4%) tube conductors have so far been removed. The reasons for removal include persistent tube ventilation disorder, dislocation of the tube conductor in 7 patients (5.6%) and granulation around the tube wire in 7 cases (5.6%). CONCLUSIONS: The chronic tube ventilation disorder was improved by implantation of a tube conductor in only 8.3% of the patient population investigated. We are therefore of the opinion that this is not a suitable treatment for chronic tube ventilation disorders. The development of new, effective therapeutic approaches to the treatment of chronic tube ventilation disorders remains a priority. PMID- 17279419 TI - [Foreign body reaction to materials implanted as biocompatible for internal fixation]. AB - After implantation of resorbable materials for internal fixation, foreign body reactions are described in 0-47% of cases. Copolymers of poly-l-lactic acid (PLLA) and polyglycolic acid (PGA) seem to offer better biocompatibility than other materials. One of our patients had a midfacial fracture, which we fixed using a resorbable system based on PLLA-PGA (82%-18%); a foreign body reaction developed after 22 months. When resorbable materials are used it is essential to be aware specifically of the risk of foreign body reactions, especially when the facial area is involved. This risk must be discussed with the patient in some detail during the preoperative period. PMID- 17279420 TI - [Chronic rhinosinusitis. Subjective assessment of benefit 1 year after functional endonasal sinus surgery]. AB - BACKGROUND: Against the background of constantly intensifying economic pressure in the healthcare sector, in the future confirmation of subjective and economic benefit of different forms of therapy will be the criterion applied by the health insurance companies to decide whether to reimburse the costs they involve. The aim of this study was to provide confirmation that patients with chronic rhinosinusitis (CRS) do benefit from functional endonasal sinus surgery (FESS). PATIENTS AND METHODS: One year after undergoing FESS for the treatment of CRS, 82 patients completed various questionnaires. The Glasgow Benefit Inventory (GBI) was used, as it is a validated instrument for the assessment of benefit. In addition, the patients were asked to complete questionnaires relating to pre- and postoperative use of resources (use of antibiotics, visits to their doctors and time unfit for work) and also to give an overall rating of their satisfaction with the outcome, the difference in their symptoms after FESS and the likelihood that they would recommend this treatment to friends or relatives. RESULTS: Three out of four GBI scales [total score (+22.6), general benefit (+26.8), physical functioning (+23.7)] indicated that patients experienced significant benefit. The frequency of visiting their doctors, their intake of antibiotics and the amount of time off work were all significantly reduced. The vast majority of patients were satisfied with the overall result and the level of symptom relief achieved and would recommend FESS to friends and relatives. CONCLUSION: The vast majority of these patients with CRS experienced FESS as highly beneficial. A significant reduction of resource usage was reported after the operation. PMID- 17279421 TI - [Bilateral nasal remission spectroscopy allows the side separated continuous measurement of changes in swelling of the nasal mucosa]. AB - INTRODUCTION: In earlier studies optical transmission spectroscopy showed that continuous monitoring of changes in the swelling of the nasal mucosa is possible. However, independent measurement in both sides of the nose cannot be achieved by this method. With the aim of achieving real-time monitoring of endonasal swelling separately for both nostrils we developed the new method of bilateral nasal remission spectroscopy for this pilot study. MATERIALS AND METHODS: In nasal remission spectroscopy, light at a wavelength of 790 nm (close to the isobestic point of hemoglobin) is beamed into each side of the nose, and the light that is backscattered by the internal nasal tissue is measured continuously on the same nasal side. To evaluate the principle of this new method a pilot study was conducted in five healthy probands subjected to a one-sided (unilateral) nasal histamine provocation test (0.14 ml, 2 mg/ml). RESULTS: In each proband single sided nasal histamine provocation led to an increase in light extinction on the provoked side by an average of 0.18 optical densities (OD). In four of the five probands a slight increase (0.04 OD) in light extinction was observed on the other side of the nose. CONCLUSION: Nasal remission spectroscopy seems to allow single-side, continuous monitoring on both sides of the nose. Therefore, the method could also be suitable for use in studies of the nasal cycle, as well as for objectivisation of nasal allergen provocation tests. PMID- 17279422 TI - Conflict between egg recognition and egg rejection decisions in common cuckoo (Cuculus canorus) hosts. AB - Common cuckoos (Cuculus canorus) are obligate brood parasites, laying eggs into nests of small songbirds. The cuckoo hatchling evicts all eggs and young from a nest, eliminating hosts' breeding success. Despite the consistently high costs of parasitism by common cuckoos, great reed warbler (Acrocephalus arundinaceus) hosts sometime accept and other times reject parasitic eggs. To explore the cognitive basis of this seemingly maladaptive variation in host responses, we documented differences in egg rejection rates within 1-day periods just before and during the egg-laying cycle across host nests. Hosts rejected cuckoo eggs at 28% of nests during the pre-egg-laying stage, but when cuckoos exchanged the first host egg with the parasite egg, rejections increased to 75%. Even later, when several host eggs remained in a nest after parasitism, rejection rate fell to 37.5%. Experimental parasitism with conspecific eggs on the first and second day of host laying showed a similar directional change in relative rejection rates, dropping from 35 to 0%. Mistakes in egg discrimination (ejection error and ejection cost) were observed mostly in the latter part of the laying cycle, mainly when nests contained 5-6 eggs. These correlational and experimental patterns of egg rejection support a cognitive process of egg discrimination through several shifts in hosts' optimal acceptance thresholds of foreign eggs. The results are also consistent with the evolution of foreign egg rejection in the context of nest-sanitation (i.e. the removal of foreign objects). Our results suggest that common cuckoo hosts may recognize more eggs than they reject. This implies that the experience of the host with one or more of its own eggs in the clutch is a key factor in rejecting parasite eggs by allowing inspection and learning about their own clutch. PMID- 17279424 TI - Deltoid flap combined with fascia lata autograft for rotator cuff defects: a histologic study. AB - The purpose of this study was to compare the histological characteristics of an autogenous fascia lata graft alone and a fascia lata graft combined with a deltoid flap in the reconstruction of rotator cuff tears. Ten New Zealand white rabbits were divided into two groups. Infraspinatus tendon defects (1 x 1 cm) were created in each animal. Reconstruction consisted of either a fascia lata graft alone or a fascia lata graft combined with a distally based deltoid flap. At 3 months, tissue harvest and histological analysis was performed. Compared to the fascia lata graft alone, there was significantly increased remodeling activity and neovascularization in the group that included a deltoid flap. Also, there was pronounced interdigitation at the graft/flap interface in the latter group. A mutually beneficial relationship may exist when an autogenous fascial graft is combined with a functional deltoid flap for reconstructing large rotator cuff defects. PMID- 17279425 TI - The role of the synovium in repairing cartilage defects. AB - The purpose of this study was to examine the role of the synovium in the transitional zone between the articular cartilage and the synovial membrane in cartilage repair and the relationship between the origin of the repaired cartilage and the grafted synovium. We used 8-week-old Sprague Dawley (SD) rats and green fluorescent protein (GFP) transgenic rats. In study 1, a full-thickness cartilage defect was created at the medial condyle of the femur, and the synovium 5 x 5 mm extending up to the cartilage defect was resected in the left knee (cartilage defect without synovium group) but not resected in the right knee (cartilage defect with intact synovium group). In study 2, after the creation of a full-thickness cartilage defect and resection of the synovium, the synovium of the GFP rats was transplanted into the unilateral knee (cartilage defect with transpl.synovium group). At 2, 4, 6, and 8 weeks after surgery, we evaluated the repaired tissue in cartilage defects histologically and immunohistochemically, and the expression of aggrecan and type II collagen in the repaired tissue was also investigated using reverse transcriptase-polymerase chain reactions (RT PCR). At 6 and 8 weeks after surgery, the defect was filled with cartilage-like tissue in cartilage defect with intact synovium group and cartilage defect with transpl.synovium group, but not in cartilage defect without synovium group. GFP positive cells were observed in the repaired tissue and the expression of aggrecan and type II collagen was found in cartilage defect with transpl.synovium group. We concluded that the synovium in the transitional zone between the articular cartilage and the grafted synovial membrane invades the cartilage defects where the cells could be detected as GFP-positive cells. Those cells may take part in the repair and may induce chondrogenesis. PMID- 17279423 TI - Inflammatory proteins in patients with obstructive sleep apnea with and without daytime sleepiness. AB - Excessive daytime sleepiness (EDS) is one of the most frequent symptoms in patients with obstructive sleep apnea syndrome (OSAS). However, not all patients with OSAS manifest EDS. The aim of this study was to assess whether differential circulatory levels of inflammatory mediators would account for differences in somnolence among patients with OSAS. Patients were prospectively recruited from referral patient cohort to the university hospital sleep center. A total of 50 consecutive patients with OSAS undergoing overnight polysomnography with or without EDS and 20 controls were evaluated. EDS was assessed using the Epworth sleepiness scale (ESS) and the multiple sleep latency test after overnight polysomnography. EDS was defined when the ESS was >10 and the mean sleep latency <10 min. Fasting blood was drawn in the morning after polysomnography. Circulating levels of tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL 6), intercellular adhesion molecule 1 (ICAM-1), 8-isoprostaglandin F2alpha (8-iso PGF2alpha), and P-selectin were measured with commercially available high sensitivity kits. Although patients with OSAS have elevated levels of ICAM-1, IL 6, and TNFalpha, there were no statistically significant differences in any of the inflammatory mediators between patients with EDS and without EDS. Emergence of EDS in the context of OSA does not appear to result from the selective increase of any particular somnogenic substance, i.e., TNFalpha, IL-6, ICAM-1, 8 iso-PGF2alpha, and P-selectin in the context of sleep-disordered breathing. PMID- 17279427 TI - A European ACL register. PMID- 17279426 TI - The patella and tibial condyle position after combined and after closing wedge high tibial osteotomy. AB - High tibial osteotomy changes the patella and tibial condyle position, which makes the subsequent total knee replacement technically demanding. From 1 January 1993 to 31 December 2000, combined osteotomy [After the first osteotomy made 2 cm distally to the joint line, a bone wedge is removed based laterally. Its tip ends at the center of the tibial condyle (half bone wedge). The distal part of the tibia is placed into the valgus position and the half bone wedge is placed into the gap opened medially.] was performed on 103 knees and closing wedge osteotomy was performed on 47 consecutive knees. Eighty combined (group A) and 41 closing wedge (group B) osteotomy were studied. All knees were assessed radiologically before surgery, in the 10th postoperative week, in the 12th postoperative month and at the time of the final follow-up (in group A-66.15 months, in group B-66.61 months). We examined the change of the femorotibial angle, of the patellar height according to the method of Insall and Salvati, of the tibial slope angle according to the method of Bonnin, of the tibial condylar offset according to the method of Yoshida and of the distance between the lateral tibial plateau and the top of the fibular head. In group A and B, the recurrence of the varus deformity was not noted and valgus alignment did not increase in any case. In group-A, the Insall-Salvati ratio remained unchanged in 65% of knees. The tibial slope angle decreased in both groups. There was correlation between the change of the tibial condylar offset and the angle of the correction in both groups. There was correlation between the change of the distance between the lateral tibial plateau and the top of the fibular head. After combined osteotomy, the transposition of the tibial condyle and the decrease of the distance between the lateral tibial plateau and the top of the fibular head was less than after closing wedge osteotomy, although the average angle of correction was more after combined osteotomy (11.835 degrees ), than after closing wedge osteotomy (9.465 degrees ). Theoretically, the recurrence of the varus deformity, the increase of the valgus alignment and (in majority of cases) the shortening of the patellar tendon do not compromise the likelihood of successful conversion to the subsequent total knee replacement, either after combined or after closing wedge osteotomy. The combined osteotomy does not lead to considerable transposition of the tibial condyle and to considerable lateral tibial bone loss; therefore, theoretically, the combined osteotomy does not impair the subsequent total knee replacement. PMID- 17279428 TI - Designing randomized clinical trials in pediatric neurosurgery. AB - OBJECTIVES: Randomized clinical trials provide the best evidence for making treatment decisions and their use in pediatric neurosurgery is increasing. In this paper, we review the basic principles of clinical trial design and discuss the unique challenges in trial design in pediatric neurosurgery. MATERIALS AND METHODS: To illustrate the basic principles of trial design and highlight the special considerations in pediatric neurosurgery, examples from the Shunt Design Trial and Endoscopic Shunt Insertion Trial were used. CONCLUSIONS: Each trial should answer one primary study question. Sample size estimates based on error rates and clinically important difference must be calculated. Allocation concealment, randomization, and blinding are critical to prevent selection and ascertainment bias. Standardization of the intervention is important to the result's validity, and study centers/surgeons should be selected on the basis of the trial objective. The effects of dropouts, crossovers, and missing data should be handled with an intention-to-treat analysis. Sample selection, informed consent, and valid outcome measures are specific challenges in the pediatric population. PMID- 17279429 TI - Undiagnosed medulloblastoma presenting as fatal hemorrhage in a 14-year-old boy: case report and review of the literature. AB - INTRODUCTION: A 14-year-old boy with no significant medical history presented to the emergency room with a sudden onset of severe headache of 1 day's duration. On admission, a non-contrast computed tomography (CT) of the head showed a posterior fossa hemorrhagic mass. MATERIALS AND METHODS: He was immediately intubated and underwent placement of an external drainage tube. A magnetic resonance imaging (MRI) was performed, which showed a large hemorrhagic mass with upward cerebellar herniation. RESULTS: Despite aggressive measures, he deteriorated and was pronounced brain dead 2 days after admission. Pathological examination of the mass revealed a medulloblastoma with extensive neuronal and astrocytic differentiation. CONCLUSION: This case represents one of the few cases of rapid, hemorrhagic expansion associated with a previously undiagnosed medulloblastoma. The topic of hemorrhage due to previously unrecognized brain tumors is discussed and the value of imaging methods used in the diagnostic assessment is emphasized. PMID- 17279430 TI - Optimised surgery (so-called TME surgery) and high-resolution MRI in the planning of treatment of rectal carcinoma. AB - BACKGROUND: Since November 1998, we have applied the concept of total mesorectal excision (TME) to rectal carcinoma together with a standardised pathological quality assessment. Participation in the European MERCURY study [The MERCURY Study Group Radiology (in press), 2006] required us to establish the indication for neoadjuvant radiochemotherapy on the basis of an magnetic resonance imaging (MRI) scan. The aim of the present retrospective study is to evaluate the quality of the surgery, the efficacy of the MRI and the oncological outcomes achieved. MATERIALS AND METHODS: Between November 2001 and October 2005, 68 out of 109 patients with carcinoma of the rectum were submitted to radical surgery in curative intent and 23/68 (34%) were given neoadjuvant therapy. In an interdisciplinary study group, each patient was evaluated pre-operatively and post-operatively using standardised MRI and histopathological methods. RESULTS: The quality of surgery was established on the basis of the pathological examination of the surgical specimen. The rates of incomplete mesorectal excision, intra-operative tumour cell dissemination and positive circumferential margins were all low at 4%, 7% and 3%, respectively. The effectiveness of MRI proved to be greatest in predicting the tumour status at the circumferential resection margin: in the admittedly limited number of patients it proved possible to correctly predict the tumour status for every patient. The assessment of the anatomic extent of the primary tumour and of the regional lymph node metastasis according to the TNM system, in contrast, was considerably less successful at 73% and 75%, and 37% and 57%, respectively. CONCLUSION: By applying the TME concept and MRI-based therapy planning, excellent results can be achieved and, at the same time, the number of patients requiring neoadjuvant treatment is considerably reduced. PMID- 17279432 TI - Exon size distribution and the origin of introns. AB - Since it was first recognised that eukaryotic genes are fragmented into coding segments (exons) separated by non-coding segments (introns), the reason for this phenomenon has been debated. There are two dominant theories: that the piecewise arrangement of genes allows functional protein domains, represented by exons, to recombine by shuffling to form novel proteins with combinations of functions; or that introns represent parasitic DNA that can infest the eukaryotic genome because it does not interfere grossly with the fitness of its host. Differing distributions of exon lengths are predicted by these two theories. In this paper we examine distributions of exon lengths for six different organisms and find that they offer empirical evidence that both theories may in part be correct. PMID- 17279431 TI - MR spectroscopy in neurodegenerative disease. AB - Unlike traditional, tracer-based methods of molecular imaging, magnetic resonance spectroscopy (MRS) is based on the behavior of specific nuclei within a magnetic field and the general principle that the resonant frequency depends on the nucleus' immediate chemical environment. Most clinical MRS research has concentrated on the metabolites visible with proton spectroscopy and measured in specified tissue volumes in the brain. This methodology has been applied in various neurodegenerative disorders, most frequently utilizing measures of N acetylaspartate as a neuronal marker. At short echo times, additional compounds can be quantified, including myo-inositol, a putative marker for neuroglia, the excitatory neurotransmitter glutamate and its metabolic counterpart glutamine, and the inhibitory neurotransmitter gamma-aminobutyric acid. 31P-MRS can be used to study high-energy phosphate metabolites, providing an in vivo assessment of tissue bioenergetic status. This review discusses the application of these techniques to patients with neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. PMID- 17279433 TI - Queen Christina's moral claim on the living: justification of a tenacious moral intuition. AB - In the long-running debate on the interest of the dead, Joan C. Callahan argues against such interests and although Soren Holm for practical reasons is prepared to consider posthumous interests, he does not see any moral basis to support such interests. He argues that the whole question is irresolvable, yet finds privacy interests where Tutankhamen is concerned. Callahan argues that there can be reasons to hold on to the fiction that there are posthumous interests, namely if it is comforting for the living and instrumental for society. Thus, despite arguing against the position that the dead have any interests or for any moral basis for such interests, these "interests" are still taken into consideration in the end. This shows the unsatisfactory basis of their positions and indicates the tenacity of the moral intuition that the dead can have moral claims on the living. One example of a posthumous interest is the interest in one's good name. Here we argue that it is an interest of moral significance. This implies that if individuals restrict use of their sample when they are still alive, those restrictions apply after their death. Further, it implies that one should be concerned with the reputation of historic persons. Research that defeats these interests calls for justification. We have suggested two lines of thinking along which such a discussion could go: investigating the truth-value of the good name and the relevance of bringing it into possible disrepute. PMID- 17279434 TI - Internal medicine residents do not accurately assess their medical knowledge. AB - BACKGROUND: Medical knowledge is essential for appropriate patient care; however, the accuracy of internal medicine (IM) residents' assessment of their medical knowledge is unknown. METHODS: IM residents predicted their overall percentile performance 1 week (on average) before and after taking the in-training exam (ITE), an objective and well accepted method to assess medical knowledge to study resident assessment accuracy. Ordinary least squares regression was used to study the association between the absolute accuracy of their predictions of their percentile performance on the ITE examination and their actual percentile performance. RESULTS: Ninety-three percent of our 28 residents participated. Residents were highly inaccurate in predicting their percentile performance. Only 31% had ITE scores that were within 10 points of their predictions. On average, most residents were pessimistic about their overall percentile performance with 18 (69%) underestimating their performance. Having just taken the examination and previous experience with the examination did not improve predictions of percentile performance. CONCLUSION: IM residents did not accurately predict their own level of medical knowledge. Taking the examination and experience with previous exams does not appear to improve the ability of these IM residents to predict their performance. Residents need to be taught to rely on the results of standardized examinations such as the ITE to best assess their overall medical knowledge. The factors important for accurate self-assessment of medical knowledge in individual clinical situations remain unexplored. PMID- 17279435 TI - The impact of haemodialysis-associated variables on lipid profile in Egyptian haemodialysis population. AB - INTRODUCTION: Haemodialysis (HD) patients appear to have particular susceptibility for cardiovascular (CV) diseases with lipid abnormalities among its significant contributors. However, there is controversy concerning the combined effect on lipid constituents during HD of the three commonly used variables; the type of heparin, dialysis membrane and the constituent of dialysate buffer bases. Consequently, this controlled prospective study was thought of. PATIENTS: Randomly 63 patients were assigned from Urology and Nephrology haemodialysis (HD) unit, Mansoura, Egypt for the planned study. Their mean age was 45.79 +/- 13.11 years. Fourteen patients with end-stage renal disease (ESRD) served as control group for the remaining 49 HD patients. They were subdivided according to the HD duration (< and > 1 year), anticoagulant used (unfractionated [UFH] and low-molecular weight heparin [LMWH, Enoxaparin), membrane type (Hemophane [HP] and polysulfone [PS] membrane) and dialysate buffer bases (bicarbonate versus acetate based). METHODS: Determining the fasting lipid value of total cholesterol (TC) and triglycerides (TG) as well as lipoproteins including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and lipoprotein (a) [Lp (a)] was completed. RESULTS: Bicarbonate dialysate was associated with significantly lower TG (134.7 +/- 11 mg/dl vs. 153 +/- 14 mg/dl, p = 0.004), higher HDL-C (33.1 +/- 3 vs. 28.3 +/- 2, p = 0.0002) and subsequently better atherosclerosis risk ratio [TC/HDL-C (ARR)] (6.02 +/- 0.09 vs. 5.3 +/- 0.9, p = 0.001) despite its insignificant effect on TC and LDL-C. However, logarithm (log) Lp (a) level was significantly higher (1.92 +/- 0.05 vs. 1.82 +/- 0.04 p = 0.001) in comparison with acetate dialysate. Membrane type was not influential in those dialyzed for < 1 year before intervention while after a year of HD, PS (n = 11) compared to HP filters (n = 11) significantly lowered TC (151.7 +/- 16 vs. 172.6 +/- 12, p = 0.003), TG (127.8 +/- 15 vs. 155.7 +/- 15, p = 0.004), LDL-C (122.1 +/- 5 vs. 130.6 +/- 7, p = 0.006) levels as well as ARR (5.9 +/- 0.5 vs. 5.4 +/- 0.3, p = 0.02). Likewise was the reduction in log Lp (a) (1.9 +/- 0.03 vs. 1.8 +/- 0.04, p = 0.002) with insignificant effect on HDL-C. After 6 months, Enoxaparin caused significant improvement of TC (0.0004), TG (p = 0.018), LDL-C (p = 0.006), HDL-C (0.041) and Lp (a) (0.047) compared to UFH. Patients who continued on Enoxaparin for 3 more months displayed an even better attenuation in most of lipid parameters whilst continuation of UFH was insignificant. Switching few patients (n = 4) from UFH to LMWH for 3 months resulted in significant lowering of TC (153 +/- 7 vs. 177.7 +/- 3, p = 0.01), TG (127.5 +/- 5 vs. 137.3 +/- 4, p = 0.03) and LDL-C (124.7 +/- 5 vs. 127.5 +/- 5, p = 0.005). However, switching equal number of patients from LMWH to UFH caused no significant change. CONCLUSION: Dyslipidaemia in Egyptian haemodialysis patients was improved when bicarbonate-based haemodialysis, the use of polysulfone membrane, and more so when the low-molecular weight heparin Enoxaparin were used. PMID- 17279437 TI - From Chlorella to chloroplasts: a personal note. AB - An historical and personal reflection on the function of the Benson-Calvin Cycle in isolated chloroplasts, the role of inorganic phosphate and the manner in which this might be best presented to students. PMID- 17279436 TI - Chemically inducible expression of the PHB biosynthetic pathway in Arabidopsis. AB - Arabidopsis plants were transformed with a multi-gene construct for expression of the polyhydroxybutyrate (PHB) biosynthetic pathway containing a gene switch that can be activated by commercially available non-steroidal ecdysone analogs approved for use on some crops as pesticides. T(1) progeny of transgenic Arabidopsis plants were isolated and screened for PHB production in the presence of ecdysone analogs. T(2) progeny derived from selected T(1) lines were subjected to further analysis by comparing PHB production levels prior to treatment with inducing agent and 21 days after initiation of induction. Significant PHB production was delayed in many of the engineered plants until after induction. PHB levels of up to 14.3% PHB per unit dry weight were observed in young leaves harvested from engineered T(2) plants after applications of the commercial ecdysone analog Mimic. PHB in older leaves reached levels of up to 7% PHB per unit dry weight. This study represents a first step towards engineering a chemically inducible gene switch for PHB production in plants using inducing agents that are approved for field use. PMID- 17279438 TI - Light-induced FTIR difference spectroscopy as a powerful tool toward understanding the molecular mechanism of photosynthetic oxygen evolution. AB - The molecular mechanism of photosynthetic oxygen evolution remains a mystery in photosynthesis research. Although recent X-ray crystallographic studies of the photosystem II core complex at 3.0-3.5 A resolutions have revealed the structure of the oxygen-evolving center (OEC), with approximate positions of the Mn and Ca ions and the amino acid ligands, elucidation of its detailed structure and the reactions during the S-state cycle awaits further spectroscopic investigations. Light-induced Fourier transform infrared (FTIR) difference spectroscopy was first applied to the OEC in 1992 as detection of its structural changes upon the S(1)- >S(2) transition, and spectra during the S-state cycle induced by consecutive flashes were reported in 2001. These FTIR spectra provide extensive structural information on the amino acid side groups, polypeptide chains, metal core, and water molecules, which constitute the OEC and are involved in its reaction. FTIR spectroscopy is thus becoming a powerful tool in investigating the reaction mechanism of photosynthetic oxygen evolution. In this mini-review, the measurement method of light-induced FTIR spectra of OEC is introduced and the results obtained thus far using this technique are summarized. PMID- 17279440 TI - New techniques for membrane protein crystallization tested on photosystem II core complex of Pisum sativum. AB - The crystallization of a given protein is a hard task being even more complicated when the protein shows a hydrophobic behavior. In the case of photosynthetic proteins, the difficulty of the experiments increased due to the high light sensitivity. Aqueous solutions of photosystem II core complex (OEC PSII) of Pisum sativum were screened for crystallization conditions using standard crystallization methods. Crystal improvement was achieved by counter-diffusion technique in single capillaries of 0.2 mm inner diameter with a three-layer configuration. The use of this advanced crystallization technique-for the first time applied to the crystallization of membrane proteins-improves the reproducibility of the experiments allowing the initial crystal characterization, and facilitates the manipulation under light protection. PMID- 17279439 TI - Chlorophyll thermofluorescence and thermoluminescence as complementary tools for the study of temperature stress in plants. AB - The photosynthetic apparatus, especially the electron transport chain imbedded in the thylakoid membrane, is one of the main targets of cold and heat stress in plants. Prompt and delayed fluorescence emission originating from photosystem II have been used, most often separately, to monitor the changes induced in the photosynthetic membranes during progressive warming or cooling of a leaf sample. Thermofluorescence of F (0) and F (M) informs on the effects of heat on the chlorophyll antennae and the photochemical centers, thermoluminescence on the stabilization and movements of charges and Delayed Light Emission on the permeability of the thylakoid membranes to protons and ions. Considered together and operated simultaneously, these techniques constitute a powerful tool to characterize the effect of thermal stress on intact photosynthetic systems and to understand the mechanisms of constitutive or induced tolerance to temperature stresses. PMID- 17279441 TI - Oxygen and light effects on the expression of the photosynthetic apparatus in Bradyrhizobium sp. C7T1 strain. AB - Photosynthetic bradyrhizobia are nitrogen-fixing symbionts colonizing the stem and roots of some leguminous plants like Aeschynomene. The effect of oxygen and light on the formation of the photosynthetic apparatus of Bradyrhizobium sp. C7T1 strain is described here. Oxygen is required for growth, but at high concentration inhibits the synthesis of bacteriochlorophyll (BChl) and of the photosynthetic apparatus. However, we show that in vitro, aerobic photosynthetic electron transport occurred leading to ADP photophosphorylation. The expression of the photosynthetic apparatus was regulated by oxygen in a manner which did not agree with earlier results in other photosynthetic bradyrhizobia since BChl accumulation was the highest under microaerobic conditions. This strain produces photosynthetic pigments when grown under cyclic illumination or darkness. However, under continuous white light illumination, a Northern blot analysis of the puf operon showed that, the expression of the photosynthetic genes of the antenna was considerable. Under latter conditions BChl accumulation in the cells was dependent on the oxygen concentration. It was not detectable at high oxygen tensions but became accumulated under low oxygen (microaerobiosis). It is known that in photosynthetic bradyrhizobia bacteriophytochrome photoreceptor (BphP) partially controls the synthesis of the photosystem in response to light. In C7T1 strain far-red light illumination did not stimulate the synthesis of the photosynthetic apparatus suggesting the presence of a non-functional BphP mediated light regulatory mechanism. PMID- 17279442 TI - Cyanobacterial NADPH dehydrogenase complexes. AB - Cyanobacteria possess functionally distinct multiple NADPH dehydrogenase (NDH-1) complexes that are essential to CO(2) uptake, photosystem-1 cyclic electron transport and respiration. The unique nature of cyanobacterial NDH-1 complexes is the presence of subunits involved in CO(2) uptake. Other than CO(2) uptake, chloroplastic NDH-1 complex has a similar role as cyanobacterial NDH-1 complexes in photosystem-1 cyclic electron transport and respiration (chlororespiration). In this mini-review we focus on the structure and function of cyanobacterial NDH 1 complexes and their phylogeny. The function of chloroplastic NDH-1 complex and characteristics of plants defective in NDH-1 are also described for comparison. PMID- 17279443 TI - Factors affecting health-related quality of life in women with recurrent breast cancer in Korea. AB - PURPOSE: The purpose was to determine the effects of recurrent breast cancer on health-related quality of life (HRQOL). METHODS: We administered the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-BR23, McGill Quality of Life Questionnaire (MQOL), Beck Depression Inventory (BDI), and Brief Fatigue Inventory (BFI) to 152 women experiencing recurrence 1 year after being diagnosed with stage I to III breast cancer. We classified recurrent women as post-, ongoing-, and non-treatment group and performed multivariate-adjusted analyses in HRQOL comparisons with data available from disease-free survivors and general population. RESULTS: Groups not completing treatment were more symptomatic and had poorer functioning in HRQOL than the post-treatment group. Compared to the general population, the post-treatment group showed worse scores concerning role, cognitive, and social functioning, fatigue, and financial difficulties. The post-treatment group showed identical scores to disease-free survivors in most HRQOL domains; however, they reported less fatigue and depression than the disease-free group. Higher overall QOL was related to absence of comorbidity, completing treatment, being involved in decision making, no problems before surgery, and good overall medical care. CONCLUSION: Treatment completed, most degraded aspects of HRQOL in recurrent breast cancer women can return to levels observed in disease-free survivors. PMID- 17279445 TI - A fundamental dual regulatory role of citrate on the biosyntheses of thuringiensin and poly-beta-hydroxybutyrate in Bacillus thuringiensis YBT-032. AB - The production of alpha-ketoglutarate, adenine, thuringiensin production rate and thuringiensin yield on glucose consumed increased by 22%, 36%, 40% and 40%, respectively, in presence of 2 g citrate/l. However, citrate decreased pyruvate production, poly-beta-hydroxybutyrate (PHB) production rate and PHB yield by 62%, 31% and 45%, respectively. The activities of pyruvate kinase and glucose-6 phosphate dehydrogenase were 36%-45% lower and 50%-120% higher than those of the control, respectively. The results suggest that citrate regulated the carbon flux to synthesis of adenine present in thuringiensin with a higher efficiency of utilization of glucose by decreasing PHB synthesis. PMID- 17279446 TI - Assessment of small ligand-protein interactions by electrophoretic mobility shift assay using DNA-modified ligand as a sensing probe. AB - The interaction between a small ligand and a protein were assessed by electrophoretic mobility shift assay. A sensing probe was created by modifying the model ligand, biotin, with DNA. The complex of DNA-modified ligand and anti biotin antibody or streptavidin as a target protein was analyzed by agarose gel electrophoresis. The band corresponding to the DNA-modified ligand was shifted in the presence of the target protein, and the intensities of the shifted bands were decreased by adding increasing concentrations of free ligand ranging from 0.1 microM to 100 microM. From this calibration the concentration of ligand in the samples could be determined, allowing for evaluation of the interaction between a small ligand and its target. PMID- 17279447 TI - Improving the yield from fermentative hydrogen production. AB - Efforts to increase H(2) yields from fermentative H(2) production include heat treatment of the inoculum, dissolved gas removal, and varying the organic loading rate. Although heat treatment kills methanogens and selects for spore-forming bacteria, the available evidence indicates H(2) yields are not maximized compared to bromoethanesulfonate, iodopropane, or perchloric acid pre-treatments and spore forming acetogens are not killed. Operational controls (low pH, short solids retention time) can replace heat treatment. Gas sparging increases H(2) yields compared to un-sparged reactors, but no relationship exists between the sparging rate and H(2) yield. Lower sparging rates may improve the H(2) yield with less energy input and product dilution. The reasons why sparging improves H(2) yields are unknown, but recent measurements of dissolved H(2) concentrations during sparging suggest the assumption of decreased inhibition of the H(2)-producing enzymes is unlikely. Significant disagreement exists over the effect of organic loading rate (OLR); some studies show relatively higher OLRs improve H(2) yield while others show the opposite. Discovering the reasons for higher H(2) yields during dissolved gas removal and changes in OLR will help improve H(2) yields. PMID- 17279444 TI - Examining predictive models of HRQOL in a population-based, multiethnic sample of women with breast carcinoma. AB - BACKGROUND: This study examined health related quality of life (HRQOL) and its predictors among African-, Asian-, Latina-, and European American breast cancer survivors (BCS) using a socio-ecologically and culturally contextual theoretical model of HRQOL. METHODS: We employed a case-control, cross sectional design with a population-based sample from the California Cancer Registry. Descriptive, bivariate, and multivariate regression analyses were conducted. RESULTS: The sample included 703 BCS: 135 (19%) African-, 206 (29%) Asian-, 183 (26%) Latina-, and 179 (26%) European Americans. Latinas reported the lowest HRQOL (p < 0.0001). The final regression model explained 70% of variance in HRQOL. Years since diagnosis, number of comorbidities, role limitation, emotional wellbeing, quality of doctor-patient relationship, social support, and life stress are significant HRQOL determinants. Exploratory regression analyses indicate ethnic differences in significant predictors for HRQOL. CONCLUSIONS: HRQOL among this multiethnic sample ranged from fair to good. Bivariate analysis suggests that ethnic differences in HRQOL exist. However, regression analyses demonstrated that socio ecological factors in conjunction with medical characteristics are more salient to HRQOL outcomes, and that ethnic group membership may be a proxy for socio ecological context. Furthermore, the influence of ethnicity, culture, and social ecology are complex; research with large, population-based samples are necessary to disentangle the impact of contextual factors on HRQOL. PMID- 17279448 TI - Cloning and functional analysis of the K+ transporter, PhaHAK2, from salt sensitive and salt-tolerant reed plants. AB - We isolated PhaHAK2 cDNAs from salt-tolerant and salt-sensitive reed plants. PhaHAK2 belongs to group II by phylogenetic analysis, and was predicted to be a high-affinity plasma membrane K(+) transporter. Yeast transformed with the PhaHAK2-u from salt-sensitive reed plants (Phragmites australis) had a decreased ability to take up K(+) in the presence of NaCl and showed a higher Na(+) permeability than yeast transformed with PhaHAK2-n or PhaHAK2-e from two salt tolerant reed plants. These results suggest a possibility that the continuous K(+) uptake by PhaHAK2 and maintenance of high K(+)/Na(+) ratio under salt stress condition is one of the causes of the salt-tolerance in reed plants. PMID- 17279449 TI - Biodegradation of chlorobenzene under hypoxic and mixed hypoxic-denitrifying conditions. AB - Pseudomonas veronii strain UFZ B549, Acidovorax facilis strain UFZ B530, and a community of indigenous groundwater bacteria, adapted to oxygen limitation, were cultivated on chlorobenzene and its metabolites 2-chloro-cis,cis-muconate and acetate/succinate under hypoxic and denitrifying conditions. Highly sensitive approaches were used to maintain defined low oxygen partial pressures in an oxygen-re-supplying headspace. With low amounts of oxygen available all cultures converted chlorobenzene, though the pure strains accumulated 3-chlorocatechol and 2-chloro-cis,cis-muconate as intermediates. Under strictly anoxic conditions no chlorobenzene transformation was observed, while 2-chloro-cis,cis-muconate, the fission product of oxidative ring cleavage, was readily degraded by the investigated chlorobenzene-degrading cultures at the expense of nitrate as terminal electron acceptor. Hence, we conclude that oxygen is an obligatory reactant for initial activation of chlorobenzene and fission of the aromatic ring, but it can be partially replaced by nitrate in respiration. The tendency to denitrify in the presence of oxygen during growth on chlorobenzene appeared to depend on the oxygen availability and the efficiency to metabolize chlorobenzene under oxygen limitation, which is largely regulated by the activity of the intradiol ring fission dioxygenase. Permanent cultivation of a groundwater consortium under reduced oxygen levels resulted in enrichment of a community almost exclusively composed of members of the beta-Proteobacteria and Bacteroidetes. Thus, it is deduced that these strains can still maintain high activities of oxygen-requiring enzymes that allow for efficient CB transformation under hypoxic conditions. PMID- 17279450 TI - Women's preferences for the provision of emergency hormonal contraception services. AB - OBJECTIVE: To elicit women's preferences for routes of supply for emergency hormonal contraception (EHC). The objectives were to identify which attributes of services women regard as important and to identify how women trade off reductions in one attribute for an improvement in another. METHOD: A stated preference discrete choice experiment. Women attending sexual health services in a Primary Care Trust in the North West of England were invited to complete a self completion questionnaire. Each respondent completed a questionnaire containing nine pair-wise choices. Demographic data were also collected. Conditional logit models were used to analyse the data. MAIN OUTCOME MEASURE: Women's preferences for, and trade-offs between, the attributes of opening hours, medical staff seen, cost of EHC, length of wait for an appointment, privacy of consultation and attitude of staff. RESULTS: Two hundred and sixty-nine women attending clinics (mean age 23.8 years, SD+/-8.69) completed the questionnaire. Almost two thirds of the sample had previously used EHC. All six attributes of EHC services were statistically significant factors influencing women's preferences for the supply of EHC. A significant proportion of women indicated on at least one occasion that they would risk pregnancy rather than choose one of the services offered to them. CONCLUSION: These results suggest that the way in which a service is configured and presented to women is likely to influence which service is chosen. In this study, women prioritised visiting a service where they would be treated in a sympathetic and non-judgemental manner. They also prioritised privacy. The results also suggest that if women are dissatisfied with aspects of an EHC service, they may choose not to visit it, thereby risking an unwanted pregnancy. PMID- 17279451 TI - Toxic mine drainage from Asia's biggest copper mine at Malanjkhand, India. AB - This paper has studied the environmental deterioration due to copper mining in Malanjkhand at Central-east India. No data is available on environmental degradation at the studied site although geological aspects are well studied. Mine drainage from the mines is definitively toxic. The site is also undergoing various stages of acid mine drainage (AMD) particularly from the heap leaching sites and the tailing area. AMD impacted water steam and sediment were also analysed. Results show substantial level of contamination of almost all segments of environment. Presence of elevated level of other heavy metal viz. Au, Ag, Pb, Cr, Cd, Fe, Cu and base metals like Na, K in AMD impacted water and sediments is due to metal leaching effect of AMD. Bio monitoring with the help of benthic macro invertebrates and metal accumulation in plants was also carried to know the impact of the toxic drainage. Results prove a very significant impact on the environmental health. PMID- 17279452 TI - Systems biology meets chromatin function: a report on the Fourth Elmau Conference on Nuclear Organization. AB - The Fourth Elmau Conference on Nuclear Organization (information, abstracts, and list with addresses of speakers at http://www.nucleararchitecture.com/) took place in Gosau, Austria, between 12 and 15 October 2006. The workshop was organized by Dean Jackson, Roel van Driel, Hans Lipps and Hans Westerhoff, and was sponsored by ABCAM, Boehringer, EMBO, and VWR. It was mainly divided into two topics: dynamic analysis of gene activation and expression, and structure and dynamics of chromatin fibres, nuclear space and epigenetics. A particular emphasis was given this time to systems biology approaches, which drove the 40 participants to extensive discussions and highly interdisciplinary scientific exchanges. Some of the concepts discussed are presented here. PMID- 17279453 TI - The Paris prospective birth cohort study: which design and who participates? AB - The Paris prospective birth cohort study was implemented in 2003 to assess environmental/behavioural factors associated with respiratory and allergic disorder occurrence in early childhood. This paper describes the design and sociodemographic features of eligible/enrolled families. Full-term newborns without any medical problem at birth were recruited in five Paris maternity hospitals. They resided in the Paris area and had French speaking mothers. Sample size is at least 3500 infants, and children are followed-up until their sixth birthday. Data collection is based on regular medical and environmental self administered questionnaires to parents. Information on dwellings is gathered by means of phone questionnaires, and standardized medical examinations are carried out at 18 months and 6 years. Exposure to traffic-related pollution is modelled. At inclusion, some information concerning refusals is gathered in order to describe sociodemographic features of participating families as compared with eligible children. 4115 (63%) out of the 6493 eligible infants are now participating in this study. Participation rate is higher in parents with a high SES (socioeconomic status), for French and European parents, and for > or =25 year-old mothers, but decreases with sibship size. Similar determinants are associated with the distribution of reasons for non-participation. The participation rate in the Paris study is comparable with other similar studies. Finally, giving detailed explanation of the study aims at inclusion, establishing regular mailed and phoned contacts with families, offering free complete medical examinations for the participant child and re-sent missing questionnaires are very important to improve participation at inclusion and during follow-up. PMID- 17279455 TI - Novelty detection--recognition and evaluation of exceptional water reflectance spectra. AB - The aim of environmental surveillance is to monitor known phenomena as well as to detect exceptional situations. Synoptic monitoring of large areas in coastal waters can be performed by remote sensing using multispectral sensors onboard satellites. Many methods are in use which enable the detection and quantification of 'standard algae' or specific algae blooms using their known spectral response. The present study focusses on the detection of spectra outside the known range and which are referred to as exceptional spectra. In a first step observations from a one-year period were used to establish the parameterisation of what is defined as 'normal.' In a second step observations from a different period were used to test the novelty detection application, i.e. to look for features not occurring in the first period. PMID- 17279456 TI - The art and science of weed mapping. AB - Land managers need cost-effective and informative tools for non-native plant species management. Many local, state, and federal agencies adopted mapping systems designed to collect comparable data for the early detection and monitoring of non-native species. We compared mapping information to statistically rigorous, plot-based methods to better understand the benefits and compatibility of the two techniques. Mapping non-native species locations provided a species list, associated species distributions, and infested area for subjectively selected survey sites. The value of this information may be compromised by crude estimates of cover and incomplete or biased estimations of species distributions. Incorporating plot-based assessments guided by a stratified-random sample design provided a less biased description of non-native species distributions and increased the comparability of data over time and across regions for the inventory, monitoring, and management of non-native and native plant species. PMID- 17279454 TI - A method to predict the metabolic effects of changes in insulin treatment in subgroups of a large population based patient cohort. AB - This case-control study was designed to analyse predictors of the effects on HbA1c levels in 4001 type 1 and type 2 diabetic patients after changing their insulin treatment. Patients from 15 outpatient diabetic clinics were treated with basal insulin and multiple injections of short-acting insulin. The effects on HbA1c of changing from NPH insulin to insulin glargine as basal insulin were studied, compared to patients continuing with NPH insulin. The following possible predictors were examined with multiple regression analysis: age, sex, type and duration of diabetes, smoking, metformin use, insulin requirement, number of basal doses per day, BMI and HbA1c at baseline. The difference between the two regression functions yielded the effect of switching treatment to insulin glargine compared to continuing with NPH insulin. Male gender, low BMI and high baseline HbA1c levels were significant predictors for a greater decrease in HbA1c when changing to insulin glargine. For example, for men with a BMI of 25 and an HbA1c of 8.0%, there was a calculated mean benefit in HbA1c of 0.26 percentage points by changing to insulin glargine, whereas women with a BMI 30 had no benefit of such a change. Thus, changing to insulin glargine had best effect in male patients with low BMI. This is one of the first studies designed to find responders to insulin treatment. Analyses of predictors may prove useful in order to tailor insulin treatment in diabetic patients in clinical practice. The clinical effects need to be confirmed in other studies and randomised controlled trials. PMID- 17279457 TI - Conservation priorities and population structure of woody medicinal plants in an area of caatinga vegetation (Pernambuco State, NE Brazil). AB - In spite of heavy harvesting pressure on some of the most popular medicinal plant species, there are very few published studies concerning their conservation the semi-arid region of northeastern Brazil. In light of this fact, the present work sought to evaluate the local conservation and the harvesting sustainability of medicinal plants in an region of caatinga vegetation employing a fusion of biological and cultural approaches. Ethnobotanical methodologies and techniques were employed in the community of "Riachao de "Malhada de Pedra"" (municipality of Caruaru, state of Pernambuco, Brazil) in order to document local knowledge concerning medicinal plants and to examine the availability of those plants in a caatinga vegetation fragment located near that community. A total of 21 medicinal plant species were identified in the area and classified according to ecological factors and local uses. Two plants (Ziziphus joazeiro and Myracrodruon urundeuva) stood out has having high priority for conservation efforts. Sixteen species were identified as having populations adequate for harvesting through a system of pre determined quotas, while four species were deemed sufficiently abundant to be harvested without risk of causing significant impact on their sustainability. PMID- 17279458 TI - Hydrogeochemical and geophysical investigation of the Istanbul Tuzla-Icmeler spring area for environmental and land use planning purposes. AB - The spring waters of Tuzla-Icmeler are on the Marmara Sea coast in Tuzla town of Istanbul city. The springs discharge a natural sodium chloride mineral water that consumed for ages for therapeutic purposes attributed to their chemical properties. Development of springs commenced during the Ottoman times and a surface collection structure was built at the discharge point of the main spring. Two deep wells were drilled to tap mineral water within the past decades. The bottled water of these springs is also sold for a couple of years and its consumption as a beverage is increasing. The geochemical properties of these springs were investigated by several researchers in the past. This study comprises geochemical and geophysical measurements performed between July 2001 and July 2002 in order to construct a conceptual hydrogeological model for environmental and land use planning purposes. The seasonal evaluation of Tuzla Icmeler (mineral spring) shows that the chemical properties fluctuate from the beginning of summer until the beginning of winter. This indicates that the overdraft of water during the summer season causes the movement and mix of normal groundwater with the mineralized groundwater. As a result, mixing of less mineralized groundwater decreases the salinity of mineralized groundwater. Using the site-specific hydrogeological, geochemical and geophysical data, zones of protection areas were delineated in order to prevent a possible pollution access to the springs and surroundings from nearby dockyards, dwellings and vehicle traffic. For this purpose, a new land use plan was proposed using the existing settlement sustainability plans. PMID- 17279459 TI - Speciation of trace metals in coastal sediments of El-Mex Bay south Mediterranean Sea-west of Alexandria (Egypt). AB - Sediments of El-Mex Bay estuary on the southern Mediterranean Sea have been analyzed for trace metals after sediment fractionation by sequential leaching. A sequential extraction procedure was applied to identify forms of Mn, Cu, Cd, Cr, Zn and Fe. The five steps of the sequential extraction procedure partitioned metals into: CH3COONH(4) extractable (F1); NaOAC carbonate extractable (F2); NH(2)OH.HCl/CH(3)COOH reducible extractable (F3); H(2)O(2)-HNO3 organic extractable (F4) and NHO3/HClO4/HF acid soluble residue (F5). Extracted concentrations of trace metals analyzed after all five steps, were found to be (mug/g) for Mn: 1930.2, Cu: 165.3, Cd: 60.9, Cr: 386.3, Zn: 2351.3 and Fe: 10895. Most of elements were found in reducible fraction except Fe found in acid soluble residue, characterizing stable compounds in sediments. Labile (non-residual) fractions of trace elements (sum of the first four fractions) were analyzed because they are more bioavailable than the residual amount. Correlation analysis was used to understand and visualize the associations between the labile fractions of trace metals and certain forms, since Fe-and Mn-oxides play an important role in trace metals sorption within aquatic systems, especially within El-Mex Bay sediments that characterized by varying metal bioavailability. PMID- 17279460 TI - Application of water quality indices and dissolved oxygen as indicators for river water classification and urban impact assessment. AB - The usefulness of water quality indices, as the indicators of water pollution, for assessment of spatial-temporal changes and classification of river water qualities was verified. Four water quality indices were investigated: WQI (considering 18 water quality parameters), WQI(min) and WQI(m) (considering five water quality parameters: temperature, pH, DO, EC and TSS) and WQI(DO) (considering a single parameter, DO). The water quality indices WQI(min), WQI(m) and WQI(DO) could be of particular interest for the developing countries because of the minimum analytical cost involved. As a case study, water quality indices were used to evaluate spatial and temporal changes of the water quality in the Bagmati river basin (Nepal) for the study period 1999-2003. The results allowed us to determine the serious negative effects of the city urban activity on the river water quality. In the studied section of the river, the water quality index (WQI) was 71 units (classified as good) at the entry station and 47.6 units (classified as bad) at the outlet station. For the studied period, a significant decrease in water quality (mean WQI decrease = 11.6%, p = 0.042) was observed in the rural areas. A comparative analysis revealed that the urban water quality was significantly bad as compared with rural. The analysis enabled to classify the water quality stations into three groups: good water quality, medium water quality and bad water quality. WQI(min) resulted in overestimation of the water quality but with similar trend as with WQI and is useful for the periodic routine monitoring program. The correlation of WQI with WQI(min) and DO resulted two new indices WQI(m) and WQI(DO), respectively. The classification of waters based on WQI(m) and WQI(DO) coincided in 90 and 93% of the samples, respectively. PMID- 17279461 TI - Leaching characteristics of heavy metals and as from two urban roadside soils. AB - The leaching tests, including the Toxicity Characteristic Leaching Procedure (TCLP), EDTA extraction and BCR sequential extractions before and after EDTA treatments, were performed on two specific soils to elucidate heavy metal associated mineral fractions and general leachability. The TCLP illustrated the low leachability of heavy metals in soils from two sites. EDTA is a strong chelator and therefore had higher extraction efficiency compared to that of TCLP. The lower extraction percentages by EDTA for As and Sb were found compared to the other heavy metals derived from anthropogenic sources. Sequential extractions showed that the importance of acid-extractable, organically-bound and Fe-Mn oxide fractions was identified for anthropogenic heavy metals with the exception of As and Ni while the importance of residual fraction was identified for endogenous metals. Changes in sequential fractions of heavy metals after leaching with EDTA are very complex and it is difficult to generalize on which fraction was more mobile than the others. These combined results are helpful in elucidating the association of heavy metals to soil fractions and the mobility characteristics of heavy metals under certain environmental conditions. PMID- 17279462 TI - Disposition kinetics, urinary excretion and dosage regimen of levofloxacin formulation following single intravenous administration in crossbred calves. PMID- 17279463 TI - Sapogenin levels in Narthecium ossifragum plants and Ovis aries lamb faeces during two alveld outbreaks in More og Romsdal, Norway, 2001. AB - The proposal that saponins produced by the lily bog asphodel (Narthecium ossifragum) may be the direct cause of the hepatogenous photosensitization disease alveld seen in Norwegian lambs was investigated by comparing sapogenin levels in two control and two toxic pastures, and in faeces from lambs grazing the four pastures in the Halsa and Surnadal municipalities, More og Romsdal county, Norway. Generally similar levels of sapogenins, determined after hydrolysis of parent plant saponins, were found in Narthecium leaves collected in June/July 2001 from the two alveld outbreak areas and two nearby control areas. Differences in the median sapogenin levels determined for leaf samples in outbreak and control areas were not statistically significant. The total level of free and conjugated sapogenins in faeces recovered from the rectums of lambs grazing the outbreak and control pastures areas varied greatly. The results obtained do not support the hypothesis that a dose-response relationship exists between Narthecium saponin levels and the occurrence of alveld outbreaks. PMID- 17279464 TI - Vitamin E and selenium supplementation reduces plasma cortisol and oxidative stress in dystocia-affected buffaloes. AB - The aim of the study was to evaluate oxidative stress around parturition in normally calved and dystocia-affected buffaloes and the clinical efficacy of vitamin E and selenium (Se) in reducing the effects in buffaloes suffering from dystocia. Plasma cortisol concentration, erythrocytic malondialdehyde (MDA) level and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated in dystocia-affected (supplemented (n = 8) and unsupplemented (n = 5) with vitamin E and Se) and normally calved (unsupplemented; n = 6) buffaloes. The decline in plasma cortisol concentration, MDA level and SOD activity was greater in the group of dystocia-affected buffaloes supplemented with vitamin E and Se (78.62 +/- 2.7%, 13.38 +/- 9.75% and 28.83 +/- 7.72%, respectively) than in the unsupplemented group (54.33 +/- 12.62%, 3.48 +/- 4.16% and 17.69 +/- 12.93%, respectively). These results suggests that supplementation with antioxidants like vitamin E and Se may be beneficial in reducing oxidative stress in dystocia-affected buffaloes in the immediate postpartum period. PMID- 17279466 TI - Nuclear morphometry in relation to lymph node status in canine mammary carcinomas. AB - The assessment of nuclear area and nuclear shape by morphometric analysis, has been investigated in 40 canine mammary carcinomas in relation to their metastatic behaviour to regional lymph-nodes. The tumours were reviewed by two experienced pathologists blinded regarding their lymph-node status, and were classified according to the histogenetically based criteria suggested by Benjamin et al. (1999). Twenty of these tumours showed lymph-node metastases (node-positive), and the other twenty were node-negative. Node-positive tumours included 6 simple adenocarcinomas, 10 ductular carcinomas, 2 anaplastic carcinomas and 2 carcinomas in mixed tumours; node-negative tumours included 18 adenocarcinomas %96, 10 simple adenocarcinomas, 8 complex adenocarcinomas %96, and 2 carcinomas in mixed tumours. Node-positive tumours showed MNA and mean SDA values significantly higher (p<0.001) than node-negative carcinomas. Data of this study, seems to confirm the importance of an histogenetically based classification in canine mammary tumours, also suggesting that morphometry may increase our prognostic performances allowing a reproducible method for detecting individual tumours with higher metastatic potential. PMID- 17279465 TI - Effect of intravenous infusion of proglumide on ruminal motility in conscious sheep (Ovis aries). AB - The effects of intravenous infusion of proglumide on regular ruminal contractions were examined in conscious sheep using doses that inhibit pancreatic exocrine secretion. After a control period of 20 min, proglumide was infused intravenously for 40 min at a dose of 15, 30 or 60 micromol/kg per min and venous blood was collected. The intravenous infusion of proglumide significantly increased the frequency of ruminal contractions at 15 micromol/kg per min without altering the amplitude, while it significantly decreased the frequency and amplitude of ruminal contractions at 30 and 60 micromol/kg per min in a dose-dependent manner. Proglumide did not increase contractile activity of the omasum, abomasum and duodenum or the plasma concentration of immunoreactive cholecystokinin (CCK). Application of proglumide at 1-30 mmol/L inhibited bethanechol-induced contraction in both longitudinal and circular muscle strips of the dorsal sac of the rumen. These results suggest that proglumide at a low dose acts indirectly on the rumen as a CCK receptor antagonist to increase the frequency of contractions, whereas at higher doses it inhibits cholinergic-induced contraction of the ruminal muscles or acts as an agonist to inhibit contractions in sheep. Hence, proglumide at high doses seems unsuitable for research or therapeutic use as a CCK receptor blockade in sheep. PMID- 17279469 TI - [Competences of medical assistants]. PMID- 17279467 TI - Can bisphosphonate treatment be stopped in a growing child with skeletal fragility? AB - Cyclical pamidronate therapy in a 2-year-old child with skeletal fragility resulted in remodelling of vertebral fractures and improvement in bone mineral density (BMD) at distal radial and spinal sites. The BMD at both sites decreased precipitously within 24 months of stopping treatment, raising the question as to whether bisphosphonates can be stopped in a growing child with skeletal fragility. INTRODUCTION: At age 23 months, a male toddler sustained a low trauma fracture of his right femur. Skeletal radiographs revealed generalised osteopenia with multiple vertebral body fractures. He was diagnosed with type IV osteogenesis imperfecta; however, no mutations were found in COL1A1 or COL1A2 genes. METHODS: This case report presents bone densitometry data before, during and after bisphosphonate treatment. Axial QCT was main outcome from 2 years of age; DXA and pQCT were taken after age 5. RESULTS: QCT confirmed that he had low spinal trabecular volumetric BMD (Z-score -2.4). After 4 years of treatment his vertebral fractures had been remodelled and all bone densitometry values (QCT, DXA and pQCT) were within normal range and therefore treatment was discontinued. Shortly after this he suffered stress fractures of his left mid tibia and at the sclerotic metaphyseal line corresponding to his first APD treatment. He had marked reduction in spinal trabecular and distal radial vBMD; change in BMAD was less marked. CONCLUSION: The patient has been restarted on IV APD therapy. This case has led us to consider whether bisphosphonate therapy can be discontinued in a child with fragility fractures before his/her linear growth has ceased? PMID- 17279470 TI - [Occupational head and neck cancer. Part I: Registered occupational diseases]. AB - Head and neck cancer can be caused by the occupational contact with cancerogenic substances, which contribute to the formation of cancer. The knowledge about those cancer entities which are frequently found under similar circumstances and working conditions, helps for getting compensation and alternatively for a realistic view when other influences--particularly lifestyle factors like smoking, alcohol and nutrition--have mainly contributed for the origin of the cancer disease. Our knowledge increases and therefore it is helpful from time to time to keep up to the state-of-art of cancer genesis. This article has two parts: part I deals with occupational cancer diseases, which are listed in a decree of the German government and part II deals with the cancer diseases, which could likely be caused by occupational factors according to latest scientific findings and are not yet listed. PMID- 17279471 TI - [Chronic ankle instability in sports -- a review for sports physicians]. AB - Chronic ankle instability represents a typical sports injury which can mostly be seen in basketball, soccer, orienteering and other high risk sports. 20 to 40 % of the acute ankle sprains develop into chronic ankle instability. From a sports orthopaedic point of view, chronic ankle instability can be subdivided into a lateral, medial or a combination of both so called rotational ankle instability. From a pathophysiological point of view, chronic ankle instability can be either mechanical with a structural ligament lesion or functional with loss of the neuromuscular control. For the sports physician, the chronic ankle instability is a difficult entity as the diagnosis is usually complex and the therapy usually surgical. This review on chronic ankle instability addresses pathomechanism, diagnostics, indications for conservative and surgical treatments, and possible long-term sequelae, as ligamentous osteoarthritis. PMID- 17279472 TI - [Patellar instability]. AB - We report a retrospective study of patients with patellar instability, all treated by operation and followed up for 3 years. Patients with recurrent dislocation of the patella, lateral displacement and primary patella dislocation were treated by a Elmslie-Trillat reconstruction combined with a soft tissue intervention. Preoperative and follow-up radiographic evaluation included weight bearing anteroposterior view and merchant view. Evaluation was done using the Insall-Salvati index, sulcus and congruence angle. The operation was performed on 23 patients. The clinical evaluation at follow-up was performed using the Knee Society- and Tegner-Score. Subjective results of the operation were excellent or good in 22 of the 23 at three years with a redislocation rate of only 1 out of 26. Most patients were able to return to the same level of sporting activity as before the injury. The technique described in this paper tries to correct as much as possible of the abnormal parameters in patellar instability to achieve a dynamic stability of the patella through the full range of motion. The excellent results are presumable explained by the use of the combined technique. PMID- 17279473 TI - [The injury pattern following the introduction of the junior premier league in Germany compared to professional senior football (soccer)]. AB - In 2003 the junior soccer premier league (U19) has been introduced in Germany to increase the competitive level in this group of age (16 - 18 years). It is the aim of this study to compare the injury pattern accompanying this new league of semi-professional junior soccer with a professional senior team. In a retrospective study all traumatic and overuse injuries, responsible for absence from practice or matches, which occurred in two seasons of one junior premier league team were recorded and analyzed. These data were compared to the injury pattern of a professional senior team based on a one-season survey. Overall, more traumatic than overuse injuries were seen. The lower extremity was predominantly affected by both. The ankle joint was the most injured joint. An injury rate of 2.89 per 1000 hours of soccer was calculated for the juniors and 2.35 for the seniors. Junior players missed 15.8 days and seniors 17.1 days of practice or match as result of an injury. Semi-professional junior and professional senior soccer share the same injury patterns with regard to injury rates and types of injuries. Therefore a professional medical care with special emphasis on prophylaxis is warranted in semi-professional junior soccer. PMID- 17279474 TI - [Injuries in women soccer - results of a prospective study - in cooperation with the German Football Association (DFB)]. AB - Within the twelve female first division soccer teams 131 players of all 254 were injured during the season 2000/01. A total of 216 injuries was found, among them 74 minor (less than a week absence from sport), 84 moderate (max. 6 weeks) and 58 major injuries (more than 6 weeks). The average time to recover after an injury was 26.5 days. Within 116 joint injuries 16 sprains and 22 ligamental ruptures of the ankle, 16 meniscal lesions and 11 ACL ruptures could be found. Women soccer shows - compared to men - a higher selective risk of severe injuries, especially to the ankle joint and cruciate ligament. The accumulation of major injuries at the beginning of the season might be due to a too great demand during the preparation. There seems to be a need of improvement of the coordinative skills and to establish proprioceptive joint exercises as a relevant part of training. PMID- 17279475 TI - [German, a language of psychiatry, is it still up to date?]. PMID- 17279476 TI - [Diagnostic and treatment of alcohol-related disorders. Results of a representative survey in counseling centers]. AB - BACKGROUND: Due to the high prevalence of alcohol related disorders (dependent, harmful and at risk drinking) the improvement of the outpatient treatment situation in this area is of major importance. The aim of this study was to examine the treatment structure and modalities of patients with alcohol related disorders in counseling centers for substance abusers based on the questioning of the counselors. METHODS: A 3-page questionnaire to characterize the institution and six standardized 10-page questionnaires (for the counselors) were sent to all counseling centers (n = 123) in Baden-Wurttemberg. The counselors were asked about diagnostic and therapeutic procedures they had employed in the last patient seen. Further questions regarded patient related and structural problems. RESULTS: The results are related to a representative sample of 262 counselors of 73 counseling centers (59.5 %). Further 28 counseling centers (22.6 %) were not able to take part in the survey because they do not care for people with alcohol related disorders. The sample complies with respect of relevant dimensions (sponsoring institution, profession of the counselors, age distribution of patients, accomplished interventions) with the population of counseling centers in Baden-Wurttemberg. The reported patients were predominantly male (80.5 %) and nearly all patients were addicted to alcohol (95.8 %). They had a mean age of 41,9 +/- 10 years, high acceptance of diagnosis (79.2 %) and treatment (80.3 %) and only 6.4 % used multiple substances. The results with respect of the diagnostic procedure refer to a structured, broad and professional procedure. 63.4 % of the counsellors are geared to formal diagnostic criteria when making a diagnosis. All relevant history elements are observed. But the study pointed towards some deficits in recognising suicidal tendencies. The own responsibility related to the supply of people with alcohol problems is predominantly seen in educational advertising and counselling, but also in numerous other areas the own responsibility is judged very high. Further training is particularly seen regarding relapse prevention and suicidality. The co-operation with several institutions, e. g. general practitioners, is judged to be relatively low. DISCUSSION: The majority of patients described by the counselors were dependent drinkers. This indicates that harmful and at risk drinkers are hardly reached by counseling centers. So there is clear space for optimizing the care for people with alcohol-related disorders. PMID- 17279477 TI - [Intracerebral haemorrhage]. PMID- 17279478 TI - In-source reduction of the azo group during matrix-assisted laser desorption/ionization time-of-flight mass spectrometry experiments. PMID- 17279479 TI - Effect of matrix crystal structure on ion abundance of carbohydrates by matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry. AB - Sample preparation techniques for carbohydrate analysis using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) are explored, with particular emphasis on analyte/matrix co-crystallization procedures. While carbohydrates are known to prefer 2,5-dihydroxybenzoic acid (2,5-DHB) as the matrix of choice, these analytes are quite specific about matrix crystal structure, which in turn is dependent on the rate of drying of analyte/matrix spots on the MALDI target. With N-acetylglucosamine (GlcNAc) and N acetylneuraminic acid (sialic acid or NeuAc) as test monosaccharides, significant increases in ion abundances are demonstrated with 2,5-DHB/NeuAc spots (>10-fold improvement) and 2,5-DHB/GlcNAc spots ( approximately 5-fold improvement) with active drying. The fine structure of crystals generated in active and passive drying was investigated using powder diffraction. Passively dried samples were shown to consist of an ordered polymorph, crystallizing in the space group P2(1)/a, while the actively dried samples produced a disordered phase crystallizing in the space group Pa. These data provide the wherewithal to engineer a matrix best suited for carbohydrate analyses. PMID- 17279480 TI - Characterization of polyether mixtures using thin-layer chromatography and matrix assisted laser desorption/ionization mass spectrometry. AB - Thin-layer chromatography (TLC) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) were combined to achieve characterization of polyether mixtures. Three polyethers, polyethylene glycol (PEG), polypropylene glycol (PPG) and polytetramethylene glycol (PTMG), or mixtures of these compounds, were studied. One shortcoming of mixture analysis of synthetic polymers using MALDI-MS is that individual polymers in the mixture may display different detection sensitivities. For example, the MALDI mass spectrum of an equimolar mixture of PEG, PPG and PTMG displayed a high intensity of PPG ions, while no PTMG ions were detectable; however, PTMG ions were detected after the mixture had been separated by TLC. This combined TLC and MALDI-MS analysis of a PPG polymer bearing reactive epoxy groups showed that the polymer contained byproducts with different end-groups. These byproducts were identified as chloro substituted polymers formed during polymer synthesis. Our study shows TLC to be a rapid and low-cost separation technique, and that it can be combined with MALDI MS to achieve effective analysis of synthetic polymers. PMID- 17279481 TI - Fragmentation study on butanolides with tandem mass spectrometry and its application for the screening of ScbR-captured quorum sensing molecules in Streptomyces coelicolor A3(2). AB - Streptomyces coelicolor has a quorum sensing (QS) system triggered by small diffusible signaling molecules, i.e. butanolides (or gamma-butyrolactones) and their cognate DNA-binding receptors. Using the DNA-binding receptors as an affinity capture matrix, the butanolides can be easily enriched and identified. For the identification and screening of the butanolides, the diagnostic peak lists generated by the tandem mass spectrometric (MS/MS) fragmentation analysis of chemically synthetic butanolides were used. In the case of using ScbR as the capture matrix, SCB1, a previously well-known butanolide, and Acl-1 (or SCB3) type butanolides having one more carbon in the acyl chain than SCB1, were detected. This is the first report directly demonstrating that Acl-1 is able to bind to ScbR in S. coelicolor. Our proposed method using both diagnostic peak lists of butanolide and the purified receptor protein as an affinity capture tool can be applied to rapidly screen QS molecules in vitro. PMID- 17279482 TI - Rapid determination of six metabolites from multiple cytochrome P450 probe substrates in human liver microsome by liquid chromatography/mass spectrometry: application to high-throughput inhibition screening of terpenoids. AB - A rapid liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the determination of six cytochrome P450 (CYP) probe substrate metabolites including paracetamol (PAR) for CYP1A2, 4-hydroxytolbutamide (OHTOL) for CYP2C9, 5-hydroxyomeprazole (OHOMe) for CYP2C19, dextrorphan (DEXM) for CYP2D6, 6-hydroxychlorzoxazone (OHCHL) for CYP2E1 and dehydronifedipine (DNIF) for CYP3A4. The triple-quadrupole mass spectrometer was operated in both positive and negative modes, and selective reaction monitoring was used for quantification. The method was validated over the concentration ranges (0.075/0.04/0.05/0.02/0.1/0.0625 microM to 4.8/2.56/3.2/1.28/6.4/4.0 microM) for PAR/OHTOL/OHOME/DEXP/OHCHL/DNIF analytes with acceptable accuracy and precision. The inhibitory effect on the six CYP enzymes has been verified with their known specific inhibitors. This high-throughput inhibition screening approach has been successfully applied to study the inhibitory effects of 18 terpenoids on CYP enzymes. Among them, tanshinone IIA and cryptotanshinone are found to be potent inhibitors to CYP1A2, while artemisinin is a marginal inhibitor to CYP1A2 and glycyrrhetic acid is a weak inhibitor to CYP2C9. PMID- 17279483 TI - Identification of intermolecular disulfide linkages in underivatised peptides using negative ion electrospray mass spectrometry. A joint experimental and theoretical study. AB - The [M--H](-) ion of a symmetrical peptide containing one intermolecular disulfide linkage cleaves through the disulfide link to produce up to four fragment anions. Two of these characteristic fragments are formed by a cleavage initiated from the Cys enolate anion on the peptide backbone. The other fragment anions are formed by a cleavage directed from an anion site on the disulfide side chain. In the case of an unsymmetrical peptide containing one intermolecular disulfide, the [M--H](-) anion may cleave through the disulfide unit to give a maximum of eight cleavage anions. These fragmentations are low-energy processes as determined by theoretical calculations carried out at the HF/6-31G(d)//AM1 level of theory. Collision-induced mass spectra of the fragment anions may provide the sequence of the peptide. PMID- 17279485 TI - Simultaneous quantification of acylcarnitine isomers containing dicarboxylic acylcarnitines in human serum and urine by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. AB - Tandem mass spectrometry (MS/MS) has become a prominent method for screening newborns for diseases such as organic acidemia and fatty acid oxidation defects, although current methods cannot separate acylcarnitine isomers. Accurate determination of dicarboxylic acylcarnitines such as methylmalonylcarnitine and glutarylcarnitine has not been carried out, because obtaining standards of these acylcarnitines is difficult. We attempted the individual determinations of acylcarnitines with isomers and dicarboxylic acylcarnitines by applying high performance liquid chromatography (HPLC). Chromatographic separation was performed by gradient elution using a mixture of 0.08% aqueous ion-pairing agent and acetonitrile as the mobile phase. Mass transitions of m/z 161.8-->84.8 for carnitine and m/z 164.8-->84.8 for deuterated carnitine were monitored in positive ion electrospray ionization mode. One carnitine and 16 acylcarnitines were quantified. The limit of quantitation (LOQ) was 0.1 micromol/L for methylmalonylcarnitine and 0.05 micromol/L for the other acylcarnitines. Intra day and inter-day coefficients of variance (CVs) were <8.3% and <8.8%, respectively, for all acylcarnitines in serum, and both were <9.2% in urine. Mean recoveries were >90% for all acylcarnitines. Human samples were quantified by this method. After addition of deuterated acylcarnitines as internal standards, acylcarnitines in serum or urine were extracted using a solid-phase extraction cartridge. In healthy adult individuals, isobutyryl-, 2-methylbutyryl- and isovalerylcarnitine were detected in serum and urine. Dicarboxylic acylcarnitines were detected in urine. High concentrations of methylmalonylcarnitine and propionylcarnitine were found in both the serum and the urine of a patient with methylmalonic acidemia. The described HPLC/MS/MS method could separate most acylcarnitine isomers and quantify them, potentially allowing detailed diagnoses and follow-up treatment for those diseases. PMID- 17279484 TI - Combined use of 2,4,6-trihydroxyacetophenone as matrix and enzymatic deglycosylation in organic-aqueous solvent systems for the simultaneous characterization of complex glycoproteins and N-glycans by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PMID- 17279486 TI - Size matters! Fragmentation chemistry of [Cu(L)n]2+ complexes of diacylglycerophosphocholines as a function of coordination number (n = 2-7). AB - [Cu(L)(n)](2+) complexes of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (L = D6PC) are formed upon electrospray ionization mass spectrometry (ESI-MS) of an 8 mM solution of D6PC with 4 mM CuCl(2) in 10 mM ammonium acetate buffer, pH 6.1. The collision-induced dissociation (CID) reactions of the [Cu(L)(n)](2+) complexes were examined in a linear ion trap mass spectrometer. A rich fragmentation chemistry was observed, including: loss of a neutral ligand; intermolecular ligand-ligand S(N)2 methylation; metal ion induced ligand fragmentation via carboxylate abstraction; and phosphate abstraction. The dominant reaction channel depends on the size (n) of the complex. Thus loss of neutral ligand(s) is the sole reaction channel for n = 5-7. At n = 4, S(N)2 methylation and carboxylate abstraction start to compete with neutral ligand loss. At n = 2 the carboxylate abstraction and phosphate abstraction reactions dominate the CID spectrum. The carboxylate abstraction and phosphate abstraction reactions are likely to be driven via neighboring group pathways. PM3 calculations, carried out to compare competing neighboring pathways based on the relative stabilities of the product ions, suggest a preference for five-membered ring formation for ligand fragmentation involving both carboxylate and phosphate abstraction. PMID- 17279488 TI - Does the electron ionization induced fragmentation of partly saturated stereoisomeric pyrrolo- and isoindoloquinazolinones show stereospecificity? AB - The electron ionization mass spectrometric behavior of pyrroloquinazolinones (1 6) and isoindoloquinazolinones (7-14) was studied. These compounds were further classified as partly saturated pyrroloquinazolinones (1-3), benzologues (7-11), methylene-bridged derivatives (4-6, 12, 13) and a bisacyl compound (14). The mass spectra of the pyrrolo- and isoindoloquinazolinones did not exhibit stereospecific retro-Diels-Alder (RDA) fragmentations. The cyclohexane-fused compounds 7 (cis annelated) and 8 (trans annelated) did display some other ions differing in their abundances that could be used to differentiate this pair of stereoisomers. Also the cyclohexene-fused compounds 2, 3, 9 and 10 exhibited somewhat different ion abundances pairwise that could be utilized for isomeric differentiation. Earlier hypothesis of pyrrolo ring cleavage via the loss of C(3)H(5)O(.) was strengthened by the fragmentation of compounds 1-4. RDA(+/-H) fragmentation is more favorable than the formation of [M-R](+) ions (R=H, C(6)H(4)CH(3), or C(6)H(4)Cl) when an unsaturated bicyclic group is present but both RDA fragmentation and [M-R](+) formation occur for cyclohexene-fused compounds, possibly because of the lower ring strain than with norbornene-fused compounds. The [M-H](+) ion was abundant for compounds 7 and 8 as was [M-Ar](+) for 1-4 and 11. Although the compounds studied might participate in amide-imidol tautomerism, no indication of such tautomerism was detected. PMID- 17279487 TI - Application of electron transfer dissociation mass spectrometry in analyses of non-enzymatically glycated peptides. AB - Non-enzymatic glycation of peptides and proteins by D-glucose has important implications in the pathogenesis of diabetes mellitus, particularly in the context of development of diabetic complications. The fragmentation behavior of glycated peptides produced from reaction of D-glucose with lysine residues was investigated by electron transfer dissociation (ETD) and collision-induced dissociation (CID) tandem mass spectrometry. It was found that high abundance ions corresponding to various degrees of neutral water losses, as well as furylium ion production, dominate the CID spectra, and that the sequence informative b and y ions were rarely observed when Amadori-modified peptides were fragmented. Contrary to what was observed under CID conditions, ions corresponding to neutral losses of water or furylium ion production were not observed in the ETD spectra. Instead, abundant and almost complete series of c- and z-type ions were observed regardless of whether the modification site was located in the middle of the sequence or close to the N-terminus, greatly facilitating the peptide sequencing. This study strongly suggests that ETD is a better technique for proteomic studies of non-enzymatically glycated peptides and proteins. PMID- 17279489 TI - Ruggedness testing of quantitative atmospheric pressure ionization mass spectrometry methods: the effect of co-injected matrix on matrix effects. AB - A number of techniques have been suggested to date for assessing matrix effects on quantitative atmospheric pressure ionization mass spectrometry (API-LC/MS) methods. A newly designed experiment has the aim of efficiently simulating the quantitative behavior of an LC/MS method as a function of the amount of co injected matrix extract. Two sets of mixtures were prepared in different formats to study matrix effects as a function of analyte or matrix amount. Chromatographic conditions were varied as well, to alter the separation between analyte and co-extractants, and thereby provide different matrix effect conditions for testing the same mixtures. Graphical presentation of the results was used to gain insight into the matrix effect phenomenon. The results suggest that ruggedness for API-LC/MS methods may be defined as the absence of significant variation in results as a function of the amount of co-injected matrix. That is, a non-rugged API-LC/MS method may give consistent results only if a fixed amount of matrix is co-injected on a specific instrument. The results also point to the existence of a specific matrix concentration for the onset of matrix effects, below which these effects are not significant. These issues are important to the US FDA Center for Veterinary Medicine, which has regulatory authority for methods used to monitor for drug residues in food tissues from animals. The ruggedness testing technique suggested here may be an important factor in determining that a method is ready for multi-laboratory testing on multiple instruments. PMID- 17279490 TI - Porous graphitic carbon chromatography/tandem mass spectrometric determination of cytarabine in mouse plasma. AB - A high-performance liquid chromatography (HPLC) system using a porous graphitic carbon (PGC) stationary phase interfaced with an electrospray ionization (ESI) source and a tandem mass spectrometer (MS/MS) for the analysis of cytarabine (ara C) in mouse plasma samples has been developed in support of a pharmacodynamic study. The graphitized carbon column was adopted for the separation of ara-C and endogenous peaks from mouse plasma samples under the reversed-phase phase mode in liquid chromatography. The retention characteristics of the PGC column and the ionization efficiencies of all analytes based on the experimental factors such as the composition of mobile phases were investigated. The potential of ionization suppression resulting from the endogenous biological matrices on the PGC column during HPLC/ESI-MS/MS was investigated using post-column infusion. The concentrations of ara-C in mouse plasma obtained by using PGC-HPLC/MS/MS and ion pairing HPLC/MS/MS were found to be in good agreement in terms of analytical accuracy. PMID- 17279491 TI - Long-term follow-up of a randomized clinical trial of non-mesh versus mesh repair of primary inguinal hernia. AB - BACKGROUND: Prospective studies and meta-analyses have indicated that non-mesh repair is inferior to mesh repair based on recurrence rates in inguinal hernia. The only reliable way to evaluate recurrence rates after hernia surgery is by long-term follow-up. METHODS: Between September 1993 and January 1996, a multicentre clinical trial was performed, in which 300 patients with unilateral primary inguinal hernia were randomized to non-mesh or mesh repair. Long-term follow-up was carried out from June 2005 to January 2006. RESULTS: Median follow up was 128 months for non-mesh and 129 months for mesh repair. The 10-year cumulative hernia recurrence rates were 17 and 1 per cent respectively (P = 0.005). Half of the recurrences developed after 3 years' follow-up. There was no significant correlation between hernia recurrence and age, level of expertise of the surgeon, contralateral hernia, obesity, history of pulmonary disease, constipation or prostate disease. CONCLUSION: After 10 years mesh repair is still superior to non-mesh hernia repair. Recurrence rates may be underestimated as recurrences continue to develop for up to 10 years after surgery. PMID- 17279492 TI - Cholesterol and serum albumin as risk factors for death in patients undergoing general surgery. AB - BACKGROUND: Serum levels of total cholesterol, its fractions (high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol) and albumin are related to a poor outcome during hospital stay. It has been not assessed whether they are related to death in the long term after general surgery. METHODS: This prospective cohort study included 2848 general surgical patients with a median follow-up of 6 years after discharge from hospital. Sampling for biochemical measurements was done at the time of admission. The outcome investigated was all-cause mortality and multivariable Cox regression was used for statistical analysis. RESULTS: Three hundred and seventy-eight patients (13.3 per cent) died during follow-up. Serum albumin (adjusted hazard ratio (HR) 2.2 (95 per cent confidence interval (c.i.) 1.5 to 3.4) for lowest versus highest quintile), total cholesterol (HR 1.6 (95 per cent c.i. 1.1 to 2.3) for lowest versus highest quintile) and HDL-C (HR 1.6 (95 per cent c.i. 1.1 to 2.4) for lowest versus highest quintile) showed a significant inverse relationship with all-cause mortality in both crude and multivariable analyses. Serum albumin and HDL-C were associated with death for up to 2 years after surgery, whereas total cholesterol had the strongest association more than 2 years after discharge. CONCLUSION: Low levels of serum albumin, total cholesterol and HDL-C are associated with death after discharge from hospital in patients having general surgery. PMID- 17279493 TI - Influence of surgical and postoperative treatment on survival in differentiated thyroid cancer. AB - BACKGROUND: The extent of thyroidectomy in patients with differentiated thyroid cancer (DTC) remains controversial. The aim of this study was to identify how surgical technique and postoperative treatments influence survival and locoregional recurrence in DTC. METHODS: A nested case-control study was conducted in a cohort of 5123 patients diagnosed with DTC in Sweden between 1958 and 1987. One matched control subject was selected randomly for each patient who died from DTC. Details regarding surgery and postoperative treatments were obtained from medical records. The effect of treatment on survival was estimated by conditional logistic regression. RESULTS: Patients not treated surgically had a poorer prognosis, but the risk of death from DTC was not affected by the choice of surgical technique. The extent of surgery influenced survival only in patients with TNM stage III disease. Locoregional recurrence resulted in a fivefold increased risk of death. Postoperative treatment was not associated with improved survival. CONCLUSION: In operated patients, the most important prognostic factor was complete removal of the tumour. The extent of removal of remaining thyroid tissue was of prognostic importance in stage III disease only. Adjuvant postoperative treatment did not influence the prognosis favourably. PMID- 17279494 TI - Parenthood after cancer - a population-based study. AB - Many cancer forms today have good prognosis, and parenthood after cancer diagnosis and treatment has become a central research topic. Previous research has mainly focused on reproductive cancers, and few population-based studies exist. The effect of several cancer forms on fertility at a population level was explored. Discrete-time hazard regression models were used to analyse register and census data for complete Norwegian birth cohorts. Men and women 17-44 years in the period 1965-2001 were included. Models for first- and higher-order birth rates, for men and women, were estimated.Overall, first-birth rates among persons with cancer were reduced by only about 25% when compared with the general population. Male cancer survivors' second- and third-birth rates were similarly reduced, whereas higher-order birth rates for females were 36% below those of the general population. Significant decreases in cancer survivors' fertility disadvantage relative to the general population were seen from 1965 to 2001. Reductions in fertility were most pronounced for reproductive cancer forms, presumably related to subfecundity. However, also cancer forms unrelated to reproductive function led to reduced fertility, perhaps suggesting underlying social mechanisms. This is further supported by the difference in probability between first and subsequent births observed for women. PMID- 17279495 TI - A comparative study of molecular dynamics in Cartesian and in internal coordinates: dynamical instability in the latter caused by nonlinearity of the equations of motion. AB - The stability of a general molecular dynamics (MD) integration scheme is examined for simulations in generalized (internal plus external) coordinates (GCs). An analytic expression is derived for the local error in energy during each integration time step. This shows that the explicit dependence of the mass-matrix on GCs, which makes the system's Lagrange equations of motion nonlinear, causes MD simulations in GCs to be less stable than those in Cartesian coordinates (CCs). In terms of CCs, the corresponding mass-matrix depends only on atomic masses and thus atomistic motion is subject to the linear Newton equations, which makes the system more stable. Also investigated are two MD methods in GCs that utilize nonzero elements of the vibrational spectroscopic B-matrices. One updates positions and velocities in GCs that are iteratively adjusted so as to conform to the velocity Verlet equivalent in GCs. The other updates positions in GCs and velocities in CCs that are adjusted to satisfy the internal constraints of the new constrained WIGGLE MD scheme. The proposed methods are applied to an isolated n-octane molecule and their performances are compared with those of several CCMD schemes. The simulation results are found to be consistent with the analytic stability analysis. Finally, a method is presented for computing nonzero elements of B-matrices for external rotations without imposing the Casimir-Eckart conditions. PMID- 17279496 TI - 2D-RNA-coupling numbers: a new computational chemistry approach to link secondary structure topology with biological function. AB - Methods for prediction of proteins, DNA, or RNA function and mapping it onto sequence often rely on bioinformatics alignment approach instead of chemical structure. Consequently, it is interesting to develop computational chemistry approaches based on molecular descriptors. In this sense, many researchers used sequence-coupling numbers and our group extended them to 2D proteins representations. However, no coupling numbers have been reported for 2D-RNA topology graphs, which are highly branched and contain useful information. Here, we use a computational chemistry scheme: (a) transforming sequences into RNA secondary structures, (b) defining and calculating new 2D-RNA-coupling numbers, (c) seek a structure-function model, and (d) map biological function onto the folded RNA. We studied as example 1-aminocyclopropane-1-carboxylic acid (ACC) oxidases known as ACO, which control fruit ripening having importance for biotechnology industry. First, we calculated tau(k)(2D-RNA) values to a set of 90 folded RNAs, including 28 transcripts of ACO and control sequences. Afterwards, we compared the classification performance of 10 different classifiers implemented in the software WEKA. In particular, the logistic equation ACO = 23.8 . tau(1)(2D-RNA) + 41.4 predicts ACOs with 98.9%, 98.0%, and 97.8% of accuracy in training, leave-one-out and 10-fold cross-validation, respectively. Afterwards, with this equation we predict ACO function to a sequence isolated in this work from Coffea arabica (GenBank accession DQ218452). The tau(1)(2D-RNA) also favorably compare with other descriptors. This equation allows us to map the codification of ACO activity on different mRNA topology features. The present computational-chemistry approach is general and could be extended to connect RNA secondary structure topology to other functions. PMID- 17279497 TI - Influence of temperature, friction, and random forces on folding of the B-domain of staphylococcal protein A: all-atom molecular dynamics in implicit solvent. AB - The influences of temperature, friction, and random forces on the folding of protein A have been analyzed. A series of all-atom molecular dynamics folding simulations with the Amber ff99 potential and Generalized Born solvation, starting from the fully extended chain, were carried out for temperatures from 300 to 500 K, using (a) the Berendsen thermostat (with no explicit friction or random forces) and (b) Langevin dynamics (with friction and stochastic forces explicitly present in the system). The simulation temperature influences the relative time scale of the major events on the folding pathways of protein A. At lower temperatures, helix 2 folds significantly later than helices 1 and 3. However, with increasing temperature, the folding time of helix 2 approaches the folding times of helices 1 and 3. At lower temperatures, the complete formation of secondary and tertiary structure is significantly separated in time whereas, at higher temperatures, they occur simultaneously. These results suggest that some earlier experimental and theoretical observations of folding events, e.g., the order of helix formation, could depend on the temperature used in those studies. Therefore, the differences in temperature used could be one of the reasons for the discrepancies among published experimental and computational studies of the folding of protein A. Friction and random forces do not change the folding pathway that was observed in the simulations with the Berendsen thermostat, but their explicit presence in the system extends the folding time of protein A. PMID- 17279498 TI - Cyclic voltammetry modeling, geometries, and electronic properties for metallofullerene complexes with mu3-eta2:eta2:eta2-C60 bonding mode. AB - Reduction potential (E(red)) values have been calculated and compared with available cyclic voltammetry (CV) data for 10 metallofullerene complexes with the mu(3)-eta(2):eta(2):eta(2)-C(60) (M(3)-C(6)[C(60)]) bonding mode. Consideration of bulk solvent effects is essential for the calculation of the E(red) values. Scaling factors for the electrostatic terms of the solvation energies have been introduced to fully describe the experimental cyclic voltammograms with a small mean deviation of 0.07 V. Multiple electron reductions induce movement of the metal cluster moieties on the C(60) surface, which is accompanied with the changes in some M-C[C(60)] bonds from pi-type to sigma-type mode. However, the changes in M(3)-C(60) distances, as well as the geometric changes of M(3) and C(60), are small for the reductions, which is in harmony with the high chemical and electrochemical stability of the metallofullerenes. Our population analyses reveal that the added electrons are not localized at the C(60) moieties, and electron population in the metal clusters is significant, more than 20% (av. 37%), for all the reductions. Furthermore, we demonstrated that the two close one electron redox waves in CV diagrams are strongly correlated with significant electron delocalization, about 40-80%, to the metal-cluster moieties in these metallofullerene complexes. PMID- 17279499 TI - A 45-ns molecular dynamics simulation of hemoglobin in water by vectorizing and parallelizing COSMOS90 on the earth simulator: dynamics of tertiary and quaternary structures. AB - Molecular dynamics (MD) simulations of human adult hemoglobin (HbA) were carried out for 45 ns in water with all degrees of freedom including bond stretching and without any artificial constraints. To perform such large-scale simulations, one of the authors (M.S.) accelerated his own software COSMOS90 on the Earth Simulator by vectorization and parallelization. The dynamical features of HbA were investigated by evaluating root-mean-square deviations from the initial X ray structure (an oxy T-state hemoglobin with PDB code: 1GZX) and root-mean square fluctuations around the average structure from the simulation trajectories. The four subunits (alpha(1), alpha(2), beta(1), and beta(2)) of HbA maintained structures close to their respective X-ray structures during the simulations even though no constraints were applied to HbA in the simulations. Dimers alpha(1)beta(1) and alpha(2)beta(2) also maintained structures close to their respective X-ray structures while they moved relative to each other like two stacks of dumbbells. The distance between the two dimers (alpha(1)beta(1) and alpha(2)beta(2)) increased by 2 A (7.4%) in the initial 15 ns and stably fluctuated at the distance with the standard deviation 0.2 A. The relative orientation of the two dimers fluctuated between the initial X-ray angle -100 degrees and about -105 degrees with intervals of a few tens of nanoseconds. PMID- 17279500 TI - "Quasi flexible" automatic docking processing for studying stereoselective recognition mechanisms, part 2: Prediction of DeltaDeltaG of complexation and 1H NMR NOE correlation. AB - The purpose of this work is to apply the global molecular interaction evaluation ("Glob-MolInE") computational protocol to the study of two molecular complexes characterized by a chiral selector and a couple of enantiomeric selectands experimentally known to give large difference in the free energy of complexation much higher than the experimental error normally associated to the molecular mechanic calculations. We have considered the well known diastereomeric complexes between the selector (S)-N-(3,5-dinitrobenzoyl)-leucine-n-propylamide (S)-1 and the selectands (R) or (S)-N-(2-naphthyl)-alanine methyl ester 2, widely studied by enantioselective HPLC, NMR and X-ray. The experimental difference of free energy of complexation between [(S)-1*(R)-2] and [(S)-1*(S)-2] (-1.34 kcal/mol) was reproduced by the new computational protocol with an excellent confidence error. Detailed results about the conformational search, the "quasi-flexible" docking and the thermodynamic estimation are presented in this work. A remarkable correlation between the theoretical results and experimental data (NOE measurements, X-ray crystallographic structure of the [(S)-1*(S)-2] complex and the free energy of complexation) supports the validity of the computational approach and underline the importance of the conformational multiplicity in the definition of the macroscopic properties of the complex in solution. PMID- 17279501 TI - Implementation of pi-pi interactions in molecular dynamics simulation. AB - No explicit pi-pi interaction term has been incorporated in the conventional molecular dynamics (MD) simulation programs in spite of its significant role in the folding of biomolecules and the clustering of organic chemicals. In this article, we propose a technique to emphasize the effect of pi-pi interactions using a function of energy and implement it into an MD simulation program. Several trial calculations show that the pi-pi incorporated program gives improved results consistent with experimental data on atom geometry and has no unfavorable interference with the conventional computational framework. This indicates an importance of the explicit consideration of pi-pi interactions in MD simulation. PMID- 17279502 TI - Effects of RF inhomogeneity at 3.0T on ramped RF excitation: application to 3D time-of-flight MR angiography of the intracranial arteries. AB - PURPOSE: To demonstrate the effects of inherent RF inhomogeneity on ramped RF excitation at 3.0T, and to introduce a simple correction for improving visualization of distal intracranial arteries in three-dimensional time-of-flight MR angiography (3D-TOF-MRA). MATERIALS AND METHODS: At 3.0T, the effects of RF inhomogeneity arising from RF interference were demonstrated for ramped RF excitation in intracranial 3D-TOF-MRA. Computer simulations and experiments on phantoms and eight normal volunteers were performed. Four different ramp shapes were tested as a possible means of countering the reduced RF field that affects the distal intracranial arteries. RESULTS: RF destructive interference alters the ramp pulse shape, which is problematic for vessels that proceed from the center to the edge of the brain. Increasing the ramp pulse slope was shown to be an effective yet simple correction to counter the falling-off of the RF field toward the periphery of the head. With this approach, circle-of-Willis 3D-TOF-MRA studies had improved distal visibility. CONCLUSION: Ramped RF excitation is severely affected by RF interference at 3.0T, which makes the ramp profile suboptimal for distal intracranial blood vessels. A simple correction of the ramp slope can make a marked improvement. PMID- 17279504 TI - Visualization of hemodynamics in intracranial arteries using time-resolved three dimensional phase-contrast MRI. AB - PURPOSE: To visualize the hemodynamics of the intracranial arteries using time resolved three-dimensional phase-contrast (PC)-MRI (4D-Flow). MATERIALS AND METHODS: MR examinations were performed with a 1.5T MR unit on six healthy volunteers (22-50 years old, average = 30 years). 4D-Flow was based on a radiofrequency (RF)-spoiled gradient-echo sequence, and velocity encoding (VENC) was performed along all three spatial directions. Measurements were retrospectively gated to the electrocardiogram (ECG), and cine series of three dimensional (3D) data sets were generated. The voxel size was 1 x 1 x 1 mm, and acquisition time was 30-40 minutes. 4D data sets were calculated into time resolved images of 3D streamlines, 3D particle traces, and 2D velocity vector fields by means of flow visualization software. RESULTS: We were able to see the 3D streamlines from the circle of Willis to the bilateral M2 segment of the middle cerebral arteries (MCAs). Time-resolved images of 3D particle traces also clearly demonstrated intracranial arterial flow dynamics. 2D velocity vector fields on the planes traversing the carotid siphon or the basilar tip were clearly visualized. These results were obtained in all six volunteers. CONCLUSION: 4D-Flow helped to elucidate the in vivo 3D hemodynamics of human intracranial arteries. This method may be a useful noninvasive means of analyzing the hemodynamics of intracranial arteries in vivo. PMID- 17279503 TI - Design and development of a prototype endocavitary probe for high-intensity focused ultrasound delivery with integrated magnetic resonance imaging. AB - PURPOSE: To integrate a high intensity focused ultrasound (HIFU) transducer with an MR receiver coil for endocavitary MR-guided thermal ablation of localized pelvic lesions. MATERIALS AND METHODS: A hollow semicylindrical probe (diameter 3.2 cm) with a rectangular upper surface (7.2 cm x 3.2 cm) was designed to house a HIFU transducer and enable acoustic contact with an intraluminal wall. The probe was distally rounded to ease endocavitary insertion and was proximally tapered to a 1.5-cm diameter cylindrical handle through which the irrigation tubes (for transducer cooling) and electrical connections were passed. MR compatibility of piezoceramic and piezocomposite transducers was assessed using gradient-echo (GRE) sequences. The radiofrequency (RF) tuning of identical 6.5 cm x 2.5 cm rectangular receiver coils on the upper surface of the probe was adjusted to compensate for the presence of the conductive components of the HIFU transducers. A T1-weighted (T1-W) sliding window dual-echo GRE sequence monitored phase changes in the focal zone of each transducer. High-intensity (2400 W/cm( 2)), short duration (<1.5 seconds) exposures produced subtherapeutic temperature rises. RESULTS: For T1-W images, signal-to-noise ratio (SNR) improved by 40% as a result of quartering the conductive surface of the piezoceramic transducer. A piezocomposite transducer showed a further 28% improvement. SNRs for an endocavitary coil in the focal plane of the HIFU trans-ducer (4 cm from its face) were three times greater than from a phased body array coil. Local shimming improved uniformity of phase images. Phase changes were detected at subtherapeutic exposures. CONCLUSION: We combined a HIFU transducer with an MR receiver coil in an endocavitary probe. SNRs were improved by quartering the conductive surface of the piezoceramic. Further improvement was achieved with a piezocomposite transducer. A phase change was seen on MR images during both subtherapeutic and therapeutic HIFU exposures. PMID- 17279505 TI - Spot counting to locate fetal cells in maternal blood and tissue: a comparison of manual and automated microscopy. AB - BACKGROUND: Fetal cell detection in maternal tissue requires an accurate, efficient, and reproducible microscopy method. Our objective was to compare manual scoring to a commercially available automated scanning system for the detection of chromosome signals by fluorescence in situ hybridization (FISH). METHODS: X and Y chromosome FISH signals were detected on slides of calibrated mixtures of blood, paraffin-embedded liver sections, and post-termination blood. For manual scoring (400x magnification), the number of cells located and duration of scoring were recorded. For automated scanning using the Metasystems Metafer3/Metafer4 Scanning System (200x magnification), duration of scanning, number of gallery images generated, duration of manual review of gallery images, and number of confirmed fetal cells were recorded. RESULTS: From all slides the number of target fetal cells located by manual and automated microscopy was highly correlated (r = 0.90). However, automated scanning required on average 4 fold more time than manual scoring (P < 0.0001), with an average automated scanning time of 9.7 h per slide compared with 2.4 h per slide when scored manually. CONCLUSIONS: In general, the accuracy of automated and manual microscopy is comparable, although manual scoring is more efficient because of the level of magnification necessary for automated scanning of cells, and a large number of gallery images generated by automated scanning that must then be reviewed manually. This suggests that when rapid analysis is required (i.e., clinical situations), manual microscopy is preferable. In contrast, automated scanning may have advantages over manual microscopy when time constraints are less imposed (i.e., research situations). PMID- 17279506 TI - Histatin-induced alterations in Candida albicans: a microscopic and submicroscopic comparison. AB - Despite the numerous studies performed in an attempt to clarify the issue, the mechanism of action of salivary histatins remains unclear. The aim of the present study was to correlate histatin-induced morphological changes in Candida albicans by fluorescence microscopy (FM), transmission electron microscopy (TEM), and high resolution scanning electron microscopy (HRSEM). Each of the fluorescent dyes used by FM (i.e., tetramethylrhodamine methyl ester perchlorate for mitochondrial potential, Lysotracker for lysosome acidic compartment, and 4',6-diamino-2 phenylindole dihydrochloride for DNA) exhibited a specific staining in control cells. Following histatin treatment, we observed a recurring staining pattern, corresponding to fluorescence concentration along the cell periphery, suggesting a loss of dye specificity. To assess histatin-induced cytoplasmic modifications, ultrastructural analysis was then carried out. After treatments with histatins, TEM revealed characteristic intracellular modifications including: vacuole overgrowth, nuclear disappearance, loss of organelle identity, as well as the appearance of electron-dense membranes, likely of mitochondrial origin. Additionally, structures resembling autophagosomes were occasionally observed. By HRSEM, mitochondrial swelling was invariably the first sign of a histatin-induced effect. Other modifications included intracellular membrane disarrangement, organelles in disarray, and a large central cavity with deformed bodies displaced to the cell periphery, similar to what was detected by TEM. In summary, our study illustrates the occurrence of ultrastructural modifications following administration of histatins. Observations made with FM, TEM, and HRSEM provided different views of the same signs, demonstrating a definite action of histatins on C. albicans morphology. The possible functional meanings of these morphological results is discussed in light of the most recent biochemical data on histatin fungicidal activity. PMID- 17279507 TI - Spatial distribution of actin and tubulin in human sperm nuclear matrix intermediate filament whole mounts-a new paradigm. AB - Sperm is a highly differentiated cell streamlined for fertilization. The function is thus heavily dependent on the cytoskeletal organization. Conventional methods limit the appreciation and correlation of this intricate cytoskeletal filament network in the context of an entire sperm. Our recent successful localization of nonmuscle myosin IIA on sperm nuclear matrix-intermediate filament (NM-IF) preparations from fertile men by embedment-free electron microscopy (EF-EM), prompted us to investigate the antigenic distribution of two major cytoskeletal proteins-actin and tubulin. The NM-IF preparations were subjected to a cocktail of buffered paraformaldehyde (2%) with a low concentration of glutaraldehyde (0.05%). These proteins were localized by indirect immunogold technique using EF EM on sperm NM-IF whole mounts. Ultrastructure analysis revealed well preserved centrioles, outer dense fibers, axonemal filaments, and submitochondrial reticulum in the sperm NM-IF. Immunoreactive actin was localized along the length of the sperm whereas beta-tubulin was present in the axoneme alone. The spatial distribution of actin and tubulin in normal human sperm NM-IF reported here together with that of myosin on whole mount offers a powerful technique to understand sperm cytoskeletal supramolecular structure. PMID- 17279508 TI - Contingency table techniques for three dimensional atom probe tomography. AB - A contingency table analysis procedure is developed and applied to three dimensional atom probe data sets for the investigation of fine-scale solute co /anti-segregation effects in multicomponent alloys. Potential sources of error and inaccuracy are identified and eliminated from the technique. The conventional P value testing techniques associated with chi(2) are shown to be unsatisfactory and can become ambiguous in cases of large block numbers or high solute concentrations. The coefficient of contingency is demonstrated to be an acceptable and useful basis of comparison for contingency table analyses of differently-conditioned materials. However, care must be taken in choice of block size and to maintain a consistent overall composition between experiments. The coefficient is dependent upon block size and solute composition, and cannot be used to compare analyses with significantly different solute compositions or to assess the extent of clustering without reference to that of the randomly ordered case. It is shown that as clustering evolves into larger precipitates and phases, contingency table analysis becomes inappropriate. Random labeling techniques are introduced to infer further meaning from the coefficient of contingency. We propose the comparison of experimental result, mu(exp), to the randomized value, micro(rand), as a new method by which to interpret the quantity of solute clustering present in a material. It is demonstrated that how this method may be utilized to identify an appropriate size of contingency table analysis blocks into which the data set is partitioned to optimize the significance of the results. PMID- 17279509 TI - Moving in the right direction-nanoimaging in cancer cell motility and metastasis. AB - Although genetic and protein manipulations have been the cornerstone for the study and understanding of biological processes for many decades, complimentary nanoscale observations have only more recently been achieved in the live-imaging mode. It is at the nano measurement level that events such as protein-protein interactions, enzymatic conversions, and single-molecule stochastic behavior take place. Therefore, nanoscale observations allow us to reinterpret knowledge from large-scale or bulk techniques and gain new insight into molecular events that has cellular, tissue, and organismal phenotypic manifestations. This review identifies pertinent questions relating to the sensing and directional component of cancer cell chemotaxis and discusses the platforms that provide insight into the molecular events related to cell motility. The study of cell motility at the molecular imaging level often necessitates the use of devices such as microinjection, microfluidics, in vivo/intravital and in vitro chemotaxis assays, as well as fluorescence methods like uncaging and FRET. The micro- and nanofabricated devices that facilitate these techniques and their incorporation to specialized microscopes such as the multiphoton, AFM, and TIR-FM, for high resolution imaging comprise the nanoplatforms used to explore the mechanisms of carcinogenesis. In real-time observations, within a milieu of physiological protein concentrations, true states of dynamic and kinetic fluxes can be monitored. PMID- 17279510 TI - Contribution of high-resolution correlative imaging techniques in the study of the liver sieve in three-dimensions. AB - Correlative microscopy has become increasingly important for the analysis of the structure, function, and dynamics of cells. This is largely due to the result of recent advances in light-, probe-, laser- and various electron microscopy techniques that facilitate three-dimensional studies. Furthermore, the improved understanding in the past decade of imaging cell compartments in the third dimension has resulted largely from the availability of powerful computers, fast high-resolution CCD cameras, specifically developed imaging analysis software, and various probes designed for labeling living and or fixed cells. In this paper, we review different correlative high-resolution imaging methodologies and how these microscopy techniques facilitated the accumulation of new insights in the morpho-functional and structural organization of the hepatic sieve. Various aspects of hepatic endothelial fenestrae regarding their structure, origin, dynamics, and formation will be explored throughout this paper by comparing the results of confocal laser scanning-, correlative fluorescence and scanning electron-, atomic force-, and whole-mount electron microscopy. Furthermore, the recent advances of vitrifying cells with the vitrobot in combination with the glove box for the preparation of cells for cryo-electron microscopic investigation will be discussed. Finally, the first transmission electron tomography data of the liver sieve in three-dimensions are presented. The obtained data unambiguously show the involvement of special domains in the de novo formation and disappearance of hepatic fenestrae, and focuses future research into the (supra)molecular structure of the fenestrae-forming center, defenestration center and fenestrae-, and sieve plate cytoskeleton ring by using advanced cryo-electron tomography. PMID- 17279511 TI - New developments in electron energy loss spectroscopy. AB - In the electron microscope, spectroscopic signals such as the characteristic X rays or the energy loss of the incident beam can provide an analysis of the local composition or electronic structure. Recent improvements in the energy resolution and sensitivity of electron spectrometers have improved the quality of spectra that can be obtained. Concurrently, the calculations used to simulate and interpret spectra have made major advances. These developments will be briefly reviewed. In recent years, the focus of analytical electron microscopy has moved away from single spectrum acquisition to mapping and imaging. In particular, the use of spectrum imaging (SI), where a full spectrum is acquired and stored at each pixel in the image is becoming widespread. A challenge for the application of spectrum imaging is the processing of such large datasets in order to extract the significant information. When we go beyond the mapping of composition and look to map bonding and electronic structure this becomes both more important and more difficult. Approaches to processing spectrum imaging data sets acquired using electron energy loss spectroscopy (EELS) will be explored in this paper. PMID- 17279512 TI - Imaging and analysis of 3-D structure using a dual beam FIB. AB - The application of focused ion beam instrumentation in the generation of three dimensional microstructural data is described. The methodologies used to acquire and manipulate this data are explained, and the technique is illustrated by a number of examples from the material sciences. The limitations of this method, and practical pointers to the generation of meaningful data, are also discussed. PMID- 17279513 TI - Characterization of prototype self-nanoemulsifying formulations of lipophilic compounds. AB - This study describes the evaluation and characterization of a self nanoemulsifying drug delivery system (SNEDDS) consisting of a nonionic surfactant (Cremophor RH40), a mixture of long chain mono-, di-, and triacylglycerides (Maisine 35-1 and Sesame oil) and ethanol. Compositions containing 10% (w/w) ethanol, 40%-60% (w/w) lipid content, and 30%-50% (w/w) Cremophor RH40 were identified as pharmaceutically relevant, robust, and self-nanoemulsifying when dispersed in aqueous media. The influence of adding three different lipophilic model drug compounds (danazol, halofantrine, and probucol) to the SNEDDS was evaluated. While danazol precipitated from the SNEDDS after dispersion in aqueous media, halofantrine and procubol remained solubilized. Halofantrine- and procubol loaded SNEDDS were evaluated in both saline and in media simulating fasted and fed-state intestinal fluid (FaSSIF and FeSSIF) using dynamic light scattering and small-angle X-ray scattering (SAXS) techniques. Stable nanoemulsions with droplet sizes in the range of 20-50 nm were formed in all media and with and without drugs. The mean size of the droplets was neither affected significantly by being dispersed into the media simulating gastro intestinal fluid, nor by addition of the drug. PMID- 17279514 TI - Fluorescence lifetime imaging of coral fluorescent proteins. AB - Corals, like many other coelenterates, contain fluorescent pigments that show considerable homology with the well known green fluorescent protein of the jellyfish Aequoria. In corals, unlike jellyfish, multiple proteins are present and the range of excitations and emissions suggest the possibility of energy transfer. The occurrence of Forster resonant energy transfer (FRET) between fluorescent proteins in corals has already been reported and time-resolved spectra have shown the effect on fluorescent lifetime, but without any spatial resolution. Lifetime confocal microscopy offers lower time resolution but excellent spatial resolution. Lifetimes of the isolated A. millepora pigments amilFP490, amilFP504, and amilFP593 (names indicate emission peaks) were 2.8, 2.9, and 2.9 ns, respectively. In the coral sample, imaging the entire emission spectrum from 420 nm, the mean lifetime was reduced to 1.5 ns, implying that FRET was occurring. Looking just at the fluorescence from FRET donors the lifetime was even shorter, at 1.3 ns, supporting this interpretation. In contrast, no reduction in lifetime is seen in the coral Euphyllia ancora, where the pigment distribution also suggests that the pigments are unlikely to be involved in photoprotection. This study set out to determine the extent of FRET between pigments in two corals, Acropora millepora and Euphyllia, ancora which differ in the arrangement of their pigments and hence possibly in pigment function. PMID- 17279515 TI - Subcellular imaging of isotopically labeled carbon compounds in a biological sample by ion microprobe (NanoSIMS). AB - Here we demonstrate the technique of nanoscale secondary ion mass spectrometry, utilizing the Cameca NanoSIMS50 ion microprobe, to detect and image the metabolism of an isotopically labeled compound (NaH(13)CO(3)) in a biological sample. In particular, we have designed and verified protocols for imaging the subcellular distribution and determining the relative abundance of labeled (13)C, within the coral Galaxea fascicularis. Analyses were conducted on 1-mum thick sections of resin-embedded material, using both scanned (mapping) and static (spot analysis) Cs(+) primary ion beam of approximately 100 nm diameter. Using these samples we establish that NanoSIMS has adequate mass resolution to reliably distinguish (13)C from potential isobaric interference by (12)C(1)H and that data extracted from ion maps are comparable to those acquired by spot analyses. Independent of the method of acquisition, ratioing of (13)C to the naturally abundant (12)C is essential if meaningful data, which can be statistically compared to standard and control samples, are to be obtained. These results highlight the potential of NanoSIMS for intracellular tracking of a variety of organic and inorganic compounds labeled with stable isotopes of C, N, O, S, P, and halogens. PMID- 17279516 TI - Evanescent fields - direct measurement, modeling, and application. AB - The evanescent field surrounding an exposed planar waveguide in silica is accurately measured using scanning near field optical microscopy (SNOM) and compared to models of the field distribution. Distortions in the field due to edge effects and the proximity of the mode to the surface are all detected. The characterized field is use to quantitatively explore the difference in collection efficiency between contact mode SNOM and intermittent contact mode SNOM. A strong correlation between tip oscillation amplitude and detection efficiency is determined. PMID- 17279517 TI - The assessment of microscopic charging effects induced by focused electron and ion beam irradiation of dielectrics. AB - Energetic beams of electrons and ions are widely used to probe the microscopic properties of materials. Irradiation with charged beams in scanning electron microscopes (SEM) and focused ion beam (FIB) systems may result in the trapping of charge at irradiation induced or pre-existing defects within the implanted microvolume of the dielectric material. The significant perturbing influence on dielectric materials of both electron and (Ga(+)) ion beam irradiation is assessed using scanning probe microscopy (SPM) techniques. Kelvin Probe Microscopy (KPM) is an advanced SPM technique in which long-range Coulomb forces between a conductive atomic force probe and the silicon dioxide specimen enable the potential at the specimen surface to be characterized with high spatial resolution. KPM reveals characteristic significant localized potentials in both electron and ion implanted dielectrics. The potentials are observed despite charge mitigation strategies including prior coating of the dielectric specimen with a layer of thin grounded conductive material. Both electron- and ion-induced charging effects are influenced by a delicate balance of a number of different dynamic processes including charge-trapping and secondary electron emission. In the case of ion beam induced charging, the additional influence of ion implantation and nonstoichiometric sputtering from compounds is also important. The presence of a localized potential will result in the electromigration of mobile charged defect species within the irradiated volume of the dielectric specimen. This electromigration may result in local modification of the chemical composition of the irradiated dielectric. The implications of charging induced effects must be considered during the microanalysis and processing of dielectric materials using electron and ion beam techniques. PMID- 17279519 TI - Introduction to NANO-MNRF: a modern Australian research facility for microscopy to the nanometer-level. PMID- 17279518 TI - Nanobeam electron diffraction and high resolution imaging analysis of InN films grown on sapphire. AB - A JEOL JEM-3000F field emission, analytical, high-resolution transmission electron microscope (HRTEM) was used to study InN films grown on sapphire substrates. It was found that, while the InN films maintained the hexagonal (wurtzite) structure, InN nanodomains with a cubic (zincblende) structure were also formed in the films. Nanobeam electron diffraction techniques were applied for identification of the cubic phase. The identification of the cubic InN was confirmed by HRTEM structural imaging. The cubic InN nanodomains are 3-10 nm in diameter, and are orientated in two different orientations with their [110](cubic) and [110](cubic) axes parallel to each other and their (111)(cubic) planes parallel to the (0001)(hex) plane of the hexagonal InN. PMID- 17279520 TI - Commentaries on the placebo concept in psychotherapy. AB - This editorial note introduces the next five commentaries on the placebo effect in psychotherapy. These commentaries follow the July, 2005 publication of a special series of articles in the Journal of Clinical Psychology, entitled "The Placebo Concept in Psychotherapy. PMID- 17279521 TI - Stability of negative self-structures: a longitudinal comparison of depressed, remitted, and nonpsychiatric controls. AB - To be considered a vulnerability marker for depression, a variable should, in addition to demonstrating sensitivity and specificity, also show evidence of temporal stability (i.e., remain present in the absence of depressive symptomatology). Although many cognitive factors are associated with depression, the majority of them appear to be episode rather than vulnerability markers. This study examined cognitive organization of positive and negative interpersonal and achievement content in clinically depressed, remitted, and nonpsychiatric controls. At initial assessment, a sample of 54 clinically depressed individuals and 37 never-depressed controls completed self-report measures of positive and negative automatic thoughts and two cognitive organizational tasks. They were retested 6 months later when half of the depressed group no longer met diagnostic criteria for major depression. Negative automatic thoughts decreased and positive automatic thoughts increased significantly in individuals who had improved clinically. The organization of negative interpersonal content remained stable despite symptom amelioration, but negative achievement content was less interconnected at follow-up in those patients who had improved. The structure of relational schemas, in particular, appears to be stable and may be an important cognitive vulnerability factor for depression. PMID- 17279522 TI - The placebo effect: "relatively large" and "robust" enough to survive another assault. AB - The evidence related to the placebo effect is discussed, and it is emphasized that the descriptors "relatively large" and "robust" are appropriate in the context in which they were used. Basic science and clinical trials, when interpreted properly, have revealed that the placebo effect is indeed a real phenomenon. J. Hunsley and R. Westmacott (this issue) as well as A. Hrobjartsson and P. C. Gotzsche (this issue) are concerned that B. E. Wampold, T. Minami, S. C. Tierney, T. W. Baskin, and K. S. Bhati (2005) overstated the clinical effects of placebo when it was never B. E. Wampold et al.'s (2005) intention to make inferences about clinical utility; however, it is shown that the placebo effect exceeds many accepted medical interventions. PMID- 17279523 TI - Performance of mentally retarded forensic patients on the test of memory malingering. AB - The utility of the Test of Memory Malingering (TOMM) with mentally retarded forensic patients was assessed. Twenty-one adjudicated forensic inpatients, who had been diagnosed with mental retardation, were administered the TOMM. The majority of these patients also suffered from an Axis I mental disorder. The participants attained a mean score of 48.7 on Trial 2, with only 1 participant scoring below the standard cutoff for malingering (i.e., 45). The participants attained a mean score of 49.4 on the Retention Trial, with no participants falling below the cutoff for malingering. The results clearly indicate that mildly retarded forensic patients can perform well on the TOMM. The findings provide evidence that the TOMM can be used in the assessment of mildly retarded criminal defendants with little fear of obtaining false indications of malingering. PMID- 17279525 TI - Interpreting the magnitude of the placebo effect: mountain or Molehill? AB - The ambiguity involved in interpreting numbers and words is central to Hrobjartsson and Gotzsche's (this issue) claim of "powerful spin" in the Wampold, Minami, Tierney, Baskin, and Bhati (2005) re-analysis of their meta-analytic findings on the placebo effect in medicine. Meta-analytic results reported by the two sets of authors are nearly identical, yet their conclusions differ dramatically. In our comment, we discuss the findings of the respective authors and consider options for representing and interpreting the magnitude of meta analytic effect size estimates. We conclude that although the meta-analyses described indicate that placebo effects do exist and cannot be dismissed as unimportant, given contextual information, it is consistent with existing research to describe the obtained mean effect size for placebos in medicine as small in magnitude. PMID- 17279524 TI - Anatomical and metabolic assessment of prostate using a 3-Tesla MR scanner with a custom-made external transceive coil: healthy volunteer study. AB - PURPOSE: To examine the possibility of using a 3 Tesla (T) magnetic resonance (MR) scanner with a custom-made external coil to obtain ductal details of the prostate, high-quality spectra, and metabolite mapping corresponding to prostate zonal anatomy in healthy volunteers. MATERIALS AND METHODS: MRI and two dimensional (2D) chemical shift imaging (CSI) were performed in 16 healthy volunteers using a 3T scanner with a custom-made external transmit-receive (transceive) coil. Visualization of the prostatic duct-like structure was analyzed on T2-weighted (T2W) images. The resolution of the metabolite peaks and the distribution of metabolites in CSI were also assessed. RESULTS: In the axial plane, 3-mm-thick images were better than 4-mm-thick images with the same voxel volume for assessing duct-like structures and prostatic urethra. Differentiation between inner and outer citrate (Cit) peaks was frequently observed (29 out of 30). The mean peak area ratio of choline (Cho) plus creatine (Cr) over Cit in the peripheral zone (PZ) was significantly lower than in the transition zone (TZ) (P = 0.014). CONCLUSION: 3T MR examinations of the prostate using an external coil allow information to be collected about the details of duct-like structures, the high-quality spectra of Cit, and the zone-specific distribution of metabolites. PMID- 17279526 TI - Good grief and not-so-good grief: countertransference in bereavement therapy. AB - This study examined the relationship between therapists' grief related to the death of a loved one and clients' perceptions of the process of bereavement therapy. Mail survey data were obtained from 69 client-therapist dyads. Results indicated that the extent to which therapists missed deceased loved ones was inversely related to client perceptions of therapist empathy, but not to client ratings of the alliance, session depth, or therapist credibility. Therapist acceptance of the death of a loved one was unrelated to any of the dependent measures. Results are discussed in terms of countertransference and its management. PMID- 17279527 TI - The story of placebo effects in medicine: evidence in context. AB - In 2005, in an article reviewing the evidence related to the placebo effect that was derived from clinical trials in medicine and psychotherapy, B. E. Wampold, T. Minami, S. C. Tierney, T. W. Baskin, and K. S. Bhati re-analyzed studies contained in A. Hrobjartsson and P. C. Gotzsche's (2001) meta-analysis of trials that contained placebo and no-treatment conditions. Whereas Hrobjartsson and Gotzsche (2001) concluded that the placebo effect was weak at best, Wampold et al. (2005) concluded that it was "robust." Hrobjartsson and Gotzsche (this issue) challenged Wampold et al.'s (2005) conclusion, claiming essentially that the results of clinical trials containing placebo and no-treatment conditions are not sufficient to claim that the placebo effect exists to any substantial degree. In this article, it is shown that when properly interpreted by considering theory, method, context, and related research, the results of clinical trials support the existence of a placebo effect. In short, the placebo effect appears in those instances where it is expected. PMID- 17279528 TI - Differential health effects of written processing of the experience of a surgical operation in high- and low-risk conditions. AB - The aim of this study was to assess the effects of the writing technique on postoperative course in interaction with different levels of risk. Participants were 40 urologic inpatients waiting to undergo transurethral resection of the prostate, with different levels of surgical risk as assessed with the Goldman Preoperative Risk Index (L. Goldman et al., 1978). Only 20 participants wrote for 3 days about the experience of being in the hospital. Measures were days of stay in the hospital after the operation, the Symptom Check List (SCL-90; L. R. Derogatis, 1977; Italian version: G. Magni, C. Messina, D. De Leo, A. Mosconi, & M. Carli, 1983) scores, and a medical evaluation of postoperative course. A significant positive effect of writing on all three dependent variables emerged only in low-risk participants. High-risk writing participants showed a nonsignificantly worse postoperative course on all parameters than did high-risk nonwriting participants. In highly stressful conditions, writing therefore should be employed only with caution. PMID- 17279529 TI - Head and neck imaging: the role of CT and MRI. AB - High-resolution computed tomography (CT) and magnetic resonance imaging (MRI) have become indispensable tools for the evaluation of conditions involving the head and neck. Complex anatomic structures and regions, such as the orbit, skull base, paranasal sinuses, deep spaces of the neck, larynx, and lymph nodes, require that the radiologist be familiar with the imaging modalities available and their appropriate applications. The purpose of this article is to review the techniques of CT and MRI and the roles they play in clinical practice, including head and neck disorders. PMID- 17279531 TI - Age dependence of cerebral perfusion assessed by magnetic resonance continuous arterial spin labeling. AB - PURPOSE: To study the normal dependence of cerebral perfusion changes on age, to measure values of perfusion early in life, and to create a reference dataset. MATERIALS AND METHODS: Perfusion maps were collected from a total of 44 healthy subjects (from four to 78 years old) using the arterial spin labeling (ASL) technique. The population was retrospectively divided into three age groups: children, teenagers, and adults. For each group, mean values of cerebral blood flow (CBF) were calculated in gray matter (GM) and white matter (WM). Results were compared across the three different age groups. RESULTS: CBF values decreased with age (97+/-5 mL/100 g/minute in GM and 26+/-1 mL/100 g/minute in WM for the children, GM 79+/-3 mL/100 g/minute and WM 22+/-1 mL/100 g/minute for the teenagers, and GM 58+/-4 mL/100 g/minute, WM 20+/-1 mL/100 g/minute for the adults). The quantitative results suggest a rapid drop, rather than a gradual decrease, in cerebral perfusion between children and adult subjects, especially in the GM. This step in CBF occurs during adolescence, at approximately the 16th year of age. CONCLUSION: ASL is a practical and quantitative technique suitable for perfusion measurement in children as well as adults. Perfusion measurements with ASL appear sensitive to neurophysiological changes occurring during brain maturation. PMID- 17279532 TI - Powerful spin in the conclusion of Wampold et al.'s re-analysis of placebo versus no-treatment trials despite similar results as in original review. AB - B. E. Wampold, T. Minami, S. C. Tierney, T. W. Baskin, and K. S. Bhati (2005) re analyzed trials included in our systematic review of randomized clinical trials that compared placebo with no treatment (A. Hrobjartsson & P. C. Gotzsche, 2001). Based on 11 trials, B. E. Wampold et al. concluded that " ... the placebo effect is robust" (p. 850). We (2001) concluded, based on 130 trials, that "we found little evidence in general that placebos have powerful clinical effects" (p. 1599). In this commentary, we examine the reasons for this discrepancy. For trials with continuous outcomes, our analyses (82 trials) and that of B. E. Wampold et al. (5 trials) resulted in pooled standardized mean differences that were small and essentially identical: -0.28 (95% confidence interval = -0.38 to 0.19) versus -0.29 (95% confidence interval = -0.52 to -0.06). There was considerable risk of bias (e.g., reporting bias, sample-size bias). Similarly, for trials with binary outcomes, our analysis (32 trials) and that of B. E. Wampold et al. (6 trials) found no statistically significant pooled effect of placebo interventions and were essentially identical: relative risk 0.95 (95% confidence interval = 0.88-1.02) versus odds ratio 0.99 (95% confidence interval = 0.81-1.23). Thus, B. E. Wampold et al.'s conclusion was not substantiated by their data, and is best characterized as powerful spin. . PMID- 17279533 TI - Cognitive-behavioral group treatment for panic disorder with agoraphobia. AB - Cognitive-behavioral therapy (CBT) is well documented in the treatment of panic disorder with or without agoraphobia; however, little is known about the efficacy of group treatment. The purpose of this open study is to investigate the benefits of a combination of the major cognitive and behavioral techniques used in the several specific versions of CBT thus far developed, in a psychotherapeutic group approach for panic and agoraphobia. Seventy-six outpatients meeting the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R; American Psychiatric Association, 1987) criteria for panic disorder with or without agoraphobia were included in the study. The treatment consisted of 14 weekly 2-hr group sessions and included: (a) an educational component, (b) interoceptive exposure, (c) cognitive restructuring, (d) problem solving, and (e) in vivo exposure. Patients achieved significant treatment gains on all dimensions assessed with a high rate of panic remission and significant improvement in the associated symptoms. Furthermore, these gains were maintained at 6-months' follow up. Our results suggest the feasibility of this combination of cognitive and behavioral techniques. The findings raise questions about the specificity and the impact of each technique. PMID- 17279534 TI - Malignant-lesion segmentation using 4D co-occurrence texture analysis applied to dynamic contrast-enhanced magnetic resonance breast image data. AB - PURPOSE: To investigate the use of four-dimensional (4D) co-occurrence-based texture analysis to distinguish between nonmalignant and malignant tissues in dynamic contrast-enhanced (DCE) MR images. MATERIALS AND METHODS: 4D texture analysis was performed on DCE-MRI data sets of breast lesions. A model-free neural network-based classification system assigned each voxel a "nonmalignant" or "malignant" label based on the textural features. The classification results were compared via receiver operating characteristic (ROC) curve analysis with the manual lesion segmentation produced by two radiologists (observers 1 and 2). RESULTS: The mean sensitivity and specificity of the classifier agreed with the mean observer 2 performance when compared with segmentations by observer 1 for a 95% confidence interval, using a two-sided t-test with alpha = 0.05. The results show that an area under the ROC curve (A(z)) of 0.99948, 0.99867, and 0.99957 can be achieved by comparing the classifier vs. observer 1, classifier vs. union of both observers, and classifier vs. intersection of both observers, respectively. CONCLUSION: This study shows that a neural network classifier based on 4D texture analysis inputs can achieve a performance comparable to that achieved by human observers, and that further research in this area is warranted. PMID- 17279535 TI - Selective maximization of (31)P MR spectroscopic signals of in vivo human brain metabolites at 3T. AB - PURPOSE: To develop a short TR, short TE, large flip angle (LFA), in vivo (31)P MR spectroscopy (MRS) technique at 3T that selectively maximizes the signal-to noise ratio (SNR) of long T(1) human brain metabolites implicated in bipolar disorder. MATERIALS AND METHODS: Two pulse sequences were evaluated for efficiency. Slice profiles acquired with the scaled, sinc-shaped, radiofrequency (RF) LFA pulses were compared to those acquired with Shinnar-Le Roux (SLR) RF LFA pulses. The SLR-based LFA pulse sequence was used to maximize the inorganic phosphate signal in a phantom, after which volunteer metabolite signals were selectively maximized and compared to their correlates acquired with conventional spin-echo methods. RESULTS: The comparison of slice profiles acquired with sinc shaped RF LFA pulses vs. SLR RF LFA pulses showed that SLR-based pulse sequences, with their improved excitation and slice profiles, yield significantly better results. In vivo LFA spin-echo MRS implemented with SLR pulses selectively increased the (31)P MRS signal, by as much as 93%, of human brain metabolites that have T(1) times longer than the TR of the acquisition. CONCLUSION: The data show that the LFA technique can be employed in vivo to maximize the signal of long T(1) (31)P brain metabolites at a given TE and TR. LFAs ranging between 120 degrees and 150 degrees are shown to maximize the (31)P signal of human brain metabolites at 3T. PMID- 17279536 TI - Evaluation of intrarenal oxygenation in mice by BOLD MRI on a 3.0T human whole body scanner. AB - PURPOSE: To extend observations on intra-renal oxygenation with blood oxygen level-dependent (BOLD) MRI in human and rats to mouse kidneys imaged with a human whole-body scanner. MATERIALS AND METHODS: Renal BOLD MRI studies were performed on a 3.0T scanner using a multiple gradient-echo (mGRE) sequence with a custom designed 2.0-cm surface coil to acquire six T(2)*-weighted images in mice (N = 8) at an in-plane resolution of 156 x 156 mum(2). BOLD MRI data were obtained before and after administration of furosemide (10 mg/kg intravenously [i.v.]). RESULTS: The mean weight of eight mice was 24.6 +/- 1.0 g. The baseline renal R(2)* (mean +/- standard error [SE]) was 28.6 +/- 2.1 seconds(-1) in the renal cortex (CO), 35.4 +/- 2.2 in the outer medulla (OM), and 21.2 +/- 2.1 seconds(-1) in the inner medulla (IM). The BOLD response to furosemide (DeltaR(2)*) was 4.1 +/- 1.4 in the CO, 10.1 +/- 2.1 seconds(-1) in the OM, and 3.4 +/- 0.8 seconds(-1) in the IM in mice. CONCLUSION: Intrarenal BOLD MR images with sufficiently high resolution can be obtained on a human whole-body scanner when combined with a small receiver coil to allow studies in mice. Both baseline R(2)* and DeltaR(2)* values following administration of furosemide were consistent with previous experience in humans and rats. PMID- 17279537 TI - Measurement of MR signal and T2* in lung to characterize a tight skin mouse model of emphysema using single-point imaging. AB - PURPOSE: To evaluate whether MRI signal and T2* measurements of lung tissue acquired at ultrashort detection times (tds) can detect emphysematous changes in lungs. MATERIALS AND METHODS: MR signal intensity of in vivo mouse lungs was measured at 4.7 T at tds of 0.2 and 0.4 msec using single-point imaging (SPI). T2* was calculated from the measurements obtained at the two tds. Two groups of 8 and 30-week-old Tight Skin (TS) and aged-matched CB57BL/6 mice were examined. The TS mice spontaneously developed emphysema-like alveolar enlargement. In vivo micro-computed tomography (microCT) scanning and histology were used as reference methods. RESULTS: MR signal and T2* were significantly lower in the lungs of TS mice than in controls. There were no significant differences between the different age groups. MR signal in lung parenchyma correlated linearly (P < 0.0001, r = 0.89) with microCT mass density, and T2* correlated linearly (P < 0.0001, r = -0.91) with the alveoli size (mean linear intercept [MLI]). CONCLUSION: The MR signal intensity and T2* measured at short tds can be used as imaging biomarkers to characterize parenchyma density and alveolar size, respectively. PMID- 17279538 TI - Novel high-throughput SNP genotyping cosegregation analysis for genetic diagnosis of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. AB - Retinitis pigmentosa (RP), the major cause of blindness in adults, is an extremely heterogeneous monogenic disorder. More than 32 causative genes have been identified, 18 of which are involved in autosomal recessive RP (arRP); however, more than 50% of the cases remain unassigned. There are no major causative genes identified for arRP nor any prevalent mutations, which make mutational screening of the already reported RP genes extremely time consuming and costly. Nonetheless, this step is unavoidable for genetic diagnosis of patients and potential carriers, and it is a prerequisite before approaching the identification of new RP genes and loci. We have designed an innovative high throughput time- and cost-effective strategy for cosegregation analysis of 22 genes of arRP and Leber congenital amaurosis (LCA; an autosomal recessive retinal dystrophy that shares some of the RP genes and traits) by SNP genotyping. This novel indirect method has been validated in a panel of 54 consanguineous and nonconsanguineous arRP families. In a single and fast genotyping step: 1) we discarded all the 22 candidate genes in 13% of the pedigrees, highlighting the families of choice to search for novel arRP genes/loci; 2) we excluded an average of 18-19 genes per family, thus diminishing the number of genes to screen for pathogenic mutations; and 3) we identified CERKL as the causative RP gene in a family in which this candidate had been previously discarded by microsatellite cosegregation analysis. This type of approach can also be applied to other nonretinal diseases with high genetic heterogeneity, such as hereditary deafness or Parkinson disease. PMID- 17279539 TI - Congenital nystagmus: randomized, controlled, double-masked trial of memantine/gabapentin. AB - OBJECTIVE: Nystagmus consists of involuntary to and fro movements of the eyes. Although studies have shown that memantine and gabapentin can reduce acquired nystagmus, no drug treatment has been systematically investigated in congenital nystagmus. METHODS: We performed a randomized, double-masked, placebo-controlled study investigating the effects of memantine and gabapentin on congenital nystagmus over a period of 56 days. The primary outcome measure was logarithmic minimum angle of resolution (logMAR) visual acuity; the secondary outcome measures were nystagmus intensity and foveation, subjective questionnaires about visual function (VF-14) and social function. Analyses were by intention to treat. RESULTS: Forty-eight patients were included in the study. One patient in the placebo group dropped out. Patients were randomized into either a memantine group (n=16), gabapentin group (n=16), or placebo group (n=15). Mean visual acuity improvements showed a significant effect between treatment groups (F=6.2; p=0.004, analysis of variance) with improvement in both memantine and gabapentin groups. Participants with afferent visual defects showed poorer improvements in visual acuity to medication than those with apparently normal visual systems. However, eye movement recordings showed that both nystagmus forms improved in nystagmus intensity (F=7.7; p=0.001) and foveation (F=8.7; p=0.0007). Participants subjectively reported an improvement in vision after memantine and gabapentin treatment more often than in the placebo group (p=0.03). However, there were no significant differences between the treatment groups with visual function (VF-14) or social function questionnaires because all groups reported improvements. INTERPRETATION: Our findings show that pharmacological agents such as memantine and gabapentin can improve visual acuity, reduce nystagmus intensity, and improve foveation in congenital nystagmus. PMID- 17279541 TI - Lack of hippocalcin causes impairment in Ras/extracellular signal-regulated kinase cascade via a Raf-mediated activation process. AB - Hippocalcin (Hpca) is a member of the neuronal calcium sensor protein family and is highly expressed in hippocampal neurons. Hpca-deficient (Hpca(-/-)) mice display a defect in cAMP response element-binding protein (CREB) activation associated with impaired spatial and associative memory. Here we examine the involvement of Hpca in the extracellular signal-regulated kinase (ERK) cascade leading to CREB activation, because application of PD98059, a broad ERK cascade inhibitor, has resulted in similar levels of CREB activation in Hpca(-/-) hippocampus. N-methyl-D-aspartate (NMDA)- and KCl-induced phosphorylation of ERK was significantly attenuated in Hpca(-/-) hippocampal slices, as was ionomycin induced phosphorylation of ERK, whereas forskolin and 12-O-tetradecanoyl-phorbol 13-acetate (TPA) stimulation yielded indistinguishable levels of ERK phosphorylation in both wild-type and Hpca(-/-) slices. In an in vitro reconstitution assay system, recombinant Hpca affected neither Raf-1 protein kinase activity with recombinant MEK-1 as a substrate nor MEK-1 kinase activity with ERK2 as a substrate. Activation of Ras by NMDA and KCl stimulation of hippocampal slices showed no obvious changes between the two genotypes; however, phosphorylation of Raf-1 was significantly lower in Hpca(-/-) slices. These results suggest that Hpca plays an important role in the activation of Raf conducted by Ras. PMID- 17279540 TI - Neocortical hyperexcitability in a human case of tuberous sclerosis complex and mice lacking neuronal expression of TSC1. AB - OBJECTIVE: To identify brain regions, cell types, or both that generate abnormal electrical discharge in tuberous sclerosis complex (TSC). Here we examined excitatory and inhibitory synaptic currents in human tissue samples obtained from a TSC patient with no discernible cortical tubers and acute neocortical brain slices from a mouse featuring synapsin-driven conditional deletion of a TSC1 gene. These studies were designed to assess whether TSC gene inactivation alters excitability. METHODS: We used visualized patch-clamp (human and mouse) and extracellular field (mouse) recordings. Additional mice were processed for immunohistochemistry or Western blot analysis. RESULTS: Detailed anatomic studies in brain tissue sections from synapsin-TSC1 conditional knock-out mice failed to uncover gross anatomic defects, loss of lamination, or frank tuber formation. However, regions of abnormal and potentially activated neocortex were shown using antibodies to nonphosphorylated neurofilaments (SMI-311) and immediate early genes (c-Fos). Extracellular recordings from neocortical slices, examining synaptic activity in these regions, demonstrated clear differences in excitability between conditional knock-out and age-matched control mice. Whole cell patch-clamp recordings demonstrated excitatory synaptic currents with strikingly long duration and epileptiform discharge patterns, similar to waveforms observed in our human tissue samples. These events were 1-amino-3 hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor mediated and were most prominent in neocortex. Normal-appearing inhibitory postsynaptic currents (human) and intrinsic neuronal firing patterns (mouse) were also recorded. INTERPRETATION: This combination of human and mouse tissue studies suggests, for the first time, that synaptic excitation is altered in a direction that favors seizure generation in TSC brain tissue regardless of cortical tubers. PMID- 17279542 TI - Acute dystonia after injection of pegylated interferon alpha-2b. PMID- 17279544 TI - Oxidative damage in nucleic acids and Parkinson's disease. AB - Oxidative DNA lesions, such as 8-oxoguanine (8-oxoG), accumulate in nuclear and mitochondrial genomes during aging, and such accumulation can increase dramatically in patients with Parkinson's disease (PD). To counteract oxidative damage to nucleic acids, human and rodents are equipped with three distinct enzymes. One of these, MTH1, hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-2'-deoxyguanosine triphosphate and 2-hydroxy-2'-deoxyadenosine triphosphate, to their monophosphate forms. The other two enzymes are 8-oxoG DNA glycosylase encoded by the OGG1 gene and adenine/2-hydroxyadenine DNA glycosylase encoded by the MUTYH gene. We have shown a significant increase in 8-oxoG in mitochondrial DNA as well as an elevated expression of MTH1, OGG1, and MUTYH in nigrostriatal dopaminergic neurons of PD patients, suggesting that the buildup of these lesions may cause dopamine neuron loss. We established MTH1-null mice and found that MTH1-null fibroblasts were highly susceptible to cell death caused by H(2)O(2) characterized by pyknosis and electron-dense deposits in the mitochondria, and that this was accompanied by an ongoing accumulation of 8-oxoG in nuclear and mitochondrial DNA. We also showed that MTH1-null mice exhibited an increased accumulation of 8-oxoG in striatal mitochondrial DNA, followed by more extreme neuronal dysfunction after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration than that of wild-type mice. In conclusion, oxidative damage in nucleic acids is likely to be a major risk factor for Parkinson's disease, indicating that a solid understanding of the defense mechanisms involved will enable us to develop new strategies for protecting the brain against oxidative stress. PMID- 17279543 TI - Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications. AB - The kynurenine pathway (KP) of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid (KYNA) and, in a competing branch, the free radical generator 3-hydroxykynurenine (3-HK) and the excitotoxin quinolinic acid (QUIN). These three "kynurenines" derive from a common precursor, L-kynurenine, and are recognized for their role in brain physiology and pathophysiology. Inhibition of kynurenine 3-hydroxylase, the enzyme responsible for 3-HK formation, shifts KP metabolism in the mature brain toward enhanced KYNA formation. We now tested the cerebral effects of kynurenine 3-hydroxylase inhibition in immature rodents. Rat pups treated with the kynurenine 3 hydroxylase inhibitor UPF 648 (30 mg/kg, i.p.) 10 min after birth showed substantial increases in cerebral and liver kynurenine and KYNA levels up to 24 hr later, whereas 3-HK and QUIN levels were simultaneously decreased. Administered to pregnant rats or mice on the last day of gestation, UPF 648 (50 mg/kg, i.p.) produced qualitatively similar changes (i.e., large increases in kynurenine and KYNA and reductions in 3-HK and QUIN) in the brain and liver of the offspring. Rat pups delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia showed further enhanced brain KYNA levels. These studies demonstrate that acute kynurenine 3-hydroxylase inhibition effectively shifts cerebral KP metabolism in neonatal rodents toward increased KYNA formation. Selective inhibitors of this enzyme may therefore provide neuroprotection in newborns and will also be useful for the experimental evaluation of the long-term effects of perinatal KP impairment. PMID- 17279545 TI - Connexin 43 gap junction proteins are up-regulated in remyelinating spinal cord. AB - Alterations in the expression of gap junction proteins have previously been observed in several diseases affecting the central nervous system; however, the status of connexin 43 (Cx43) has not yet been reported in spinal cord remyelination. We studied Cx43 expression in demyelination and remyelination by using a chronic guinea pig model of experimental allergic encephalomyelitis (EAE). Hartley guinea pigs were immunized with homogenized whole CNS and complete Freund's adjuvant. Animals became chronically ill by day 40 postimmunization, and animals with paralysis were entered into the study. Animals were treated on days 40-60 postimmunization with either saline or drugs that promote remyelination: an adenosine amine congener (100 mug/kg), an anti-alpha4-integrin blocker (CT301; ELN 69299; 30 mg/kg), or a combination of both drugs. Remyelination was induced in all drug-treated groups. Cx43 expression was virtually absent in demyelinated lesions of saline-treated controls compared with healthy tissue and normal appearing white matter (P < 0.001), whereas Cx43 was considerably increased (300 500%) in remyelinating lesions of all treatment groups (P < 0.001), most notably in CT301-treated animals. These changes in Cx43 expression indicate that Cx43 may beimportant for recovery from neuroinflammation. PMID- 17279546 TI - Intermediate chain subunit as a probe for cytoplasmic dynein function: biochemical analyses and live cell imaging in PC12 cells. AB - Cytoplasmic dynein 1 is a multi-subunit motor protein responsible for microtubule minus end-directed transport in axons. The cytoplasmic dynein intermediate chain subunit has a scaffold-like role in the dynein complex; it directly binds to four of the other five subunits, the heavy chain and the three light chains. The intermediate chain also binds the p150 subunit of dynactin, a protein that is essential for many dynein functions. We reexamined the generation of rat cytoplasmic dynein intermediate chain isoforms by the alternative splicing of the two genes that encode this subunit and identified an additional splicing site in intermediate chain gene 1. We reinvestigated the expression of the intermediate chain 1 isoforms in cultured cells and tissues. The Loa mouse, which is homozygote lethal, contains a missense mutation in the region of the cytoplasmic dynein heavy chain gene that binds the intermediate chain. Protein binding studies showed that all six intermediate chains were able to bind to the mutated heavy chain. GFP-tagged intermediate chains were constructed and PC12 cell lines with stable expression of the fusion proteins were established. Live cell imaging and comparative immunocytochemical analyses show that dynein is enriched in the actin rich region of growth cones. PMID- 17279547 TI - Classification of missense variants of unknown significance in BRCA1 based on clinical and tumor information. AB - Classification of rare missense variants in disease susceptibility genes as neutral or disease-causing is important for genetic counseling. Different criteria are used to help classify such variants in BRCA1 and BRCA2; however, the strongest evidence tends to come from segregation analysis and observed cooccurrence with known pathogenic mutations, which both require information that is not readily available in most circumstances. A likelihood-based model has been developed, integrating most of the data currently used to classify these variants. We have adapted the original model, including only that information that could be more easily obtained from a cancer genetics laboratory, such as loss of heterozygosity (LOH), grade, and immunohistochemical analysis to assess estrogen receptor (ER) status for the tumors of carriers of these variants. We also considered summary family history (personal or first-degree family history of bilateral breast or ovarian cancer), which was not incorporated into the original model. To test the ability of the modified model to classify missense variants in BRCA1, we analyzed 17 variants, of which 10 have previously been classified as pathogenic mutations or neutral polymorphisms. We also included a prior step consisting of the screening of the variants among 1,000 controls, with which we were able to classify five as neutral, based solely on their observed frequency. We found that combining this relatively easily collected information can be sufficient to classify variants as pathogenic or neutral if tumors from at least three carriers of the same variant can be collected and analyzed. PMID- 17279548 TI - Accuracy of distributed multipoles and polarizabilities: comparison between the LoProp and MpProp models. AB - Localized multipole moments up to the fifth moment as well as localized dipole polarizabilities are calculated with the MpProp and the newly developed LoProp methods for a total of 20 molecules, predominantly derived from amino acids. A comparison of electrostatic potentials calculated from the multipole expansion obtained by the two methods with ab initio results shows that both methods reproduce the electrostatic interaction with an elementary charge with a mean absolute error of approximately 1.5 kJ/mol at contact distance and less than 0.1 kJ/mol at distances 2 A further out when terms up to the octupole moments are included. The polarizabilities are tested with homogenous electric fields and are found to have similar accuracy. The MpProp method gives better multipole moments unless diffuse basis sets are used, whereas LoProp gives better polarizabilities. PMID- 17279549 TI - Quantum mechanical/molecular mechanical simulations of the Tl(III) ion in water. AB - Classical molecular dynamics (MD) and combined quantum mechanical/molecular mechanical (QM/MM) MD simulations have been performed to investigate the structural and dynamical properties of the Tl(III) ion in water. A six-coordinate hydration structure with a maximum probability of the Tl-O distance at 2.21 A was observed, which is in good agreement with X-ray data. The librational and vibrational spectra of water molecules in the first hydration shell are blue shifted compared with those of pure liquid water, and the Tl-O stretching force constant was evaluated as 148 Nm(-1). Both structural and dynamical properties show a distortion of the first solvation shell structure. The second shell ligands' mean residence time was determined as 12.8 ps. The Tl(III) ion can be classified as "structure forming" ion; the calculated hydration energy of -986 +/ 9 kcal mol agrees well with the experimental value of -986 kcal mol. PMID- 17279550 TI - Comprehensive evaluation of allele frequency differences of MC1R variants across populations. AB - The melanocortin 1 receptor (MC1R), a member of the G protein-coupled receptors superfamily, mediates the response to melanocortins and is currently the best described contributor to normal pigment variation in humans. A remarkably large number of natural polymorphisms, or variants, of the MC1R gene have been identified in different populations. Some of these variants have been associated with specific hair and skin color phenotypes, the presence of freckling, and melanoma and nonmelanoma skin cancer risk. Interestingly, some MC1R variants have been associated with skin cancer beyond their effects on pigmentation. Although the red hair color variants (RHC variants) have been associated with skin cancer risk in the Celtic population, studies in darkly-pigmented Caucasian populations have demonstrated the importance of non-RHC MC1R variants on skin cancer risk as well. We have reviewed and compared allele frequency differences of MC1R variants across geographic regions. We observed large differences in the distribution of variants across populations, with a prominent difference between lightly and darkly-pigmented individuals. Moreover, among Caucasian groups, there were seven variants (p.V60L, p.V92M, p.D84E, p.R151C, p.R160W, p.R163Q, and p.D294H) with significantly different allele frequencies. Exploring differences in allele frequencies of MC1R variants across populations with varying pigmentation and differing skin cancer risk may improve our understanding of the complex relationship between MC1R, pigmentation, and carcinogenesis. PMID- 17279552 TI - Cyclic guanosine monophosphate signalling pathway plays a role in neural cell adhesion molecule-mediated neurite outgrowth and survival. AB - The neural cell adhesion molecule (NCAM) plays a crucial role in neuronal development, regeneration, and synaptic plasticity associated with learning and memory consolidation. Homophilic binding of NCAM leads to neurite extension and neuroprotection in various types of primary neurons through activation of a complex network of signalling cascades, including fibroblast growth factor receptor, Src-family kinases, the mitogen-activated protein kinase pathway, protein kinase C, phosphatidylinositol-3 kinase, and an increase in intracellular Ca(2+). Here we present data indicating an involvement of cyclic GMP in NCAM mediated neurite outgrowth in both hippocampal and dopaminergic neurons and in NCAM-mediated neuroprotection of dopaminergic neurons. In addition, evidence is presented suggesting that NCAM mediates activation of cGMP via synthesis of nitric oxide (NO) by NO synthase (NOS) and activation of soluble guanylyl cyclase by NO, leading to an increased synthesis of cGMP and activation by cGMP of protein kinase G. PMID- 17279554 TI - Differential expression of tissue inhibitor of metalloproteinases-3 in cultured astrocytes and neurons regulates the activation of matrix metalloproteinase-2. AB - Matrix metalloproteinases (MMPs) degrade the extracellular matrix and are implicated in the pathogenesis of several neurological diseases. Secreted in proforms, the MMPs require activation. Tissue inhibitors of matrix metalloproteinases (TIMPs) regulate the activity of MMPs. We investigated the expression of MMP-2 and -9, and the role of the TIMP-3 in MMP-2 activation, using cultures of cortical neurons and astrocytes. Under basal conditions, astrocytes and neurons produced low levels of pro-MMP-2, and -9. Stimulation with lipopolysaccharide (LPS) markedly increased pro-MMP-9 production in astrocytes, with only a slight increase in neurons. Pro-MMP-2 were constitutively expressed in both cell types, but with a much higher level in the astrocytes. Real-time RT PCR showed that the mRNA levels of MMP-2 and -9 paralleled their gelatinolytic activities in the gelatin zymograms. Interestingly, active MMP-2 was observed only in neuronal cultures. TIMP-2 and TIMP-3 are constitutively expressed in astrocytes and neurons. However, astrocytes expressed much higher levels of TIMP 3 mRNA and protein than neurons. Knockdown of TIMP-3 with small interfering RNA (siRNA) significantly increased MMP-2 activation in astrocytes. These results indicate that astrocytes are a more important intrinsic cellular source of MMP-2 and -9 than neurons under normal and neuroinflammatory conditions. TIMP-3 may be the key factor determining the differential activation of MMP-2 in astrocytes and neurons. PMID- 17279553 TI - Insulin-like growth factor-I ameliorates demyelination induced by tumor necrosis factor-alpha in transgenic mice. AB - Our groups have reported that tumor necrosis factor-alpha (TNF-alpha) causes myelin damage and apoptosis of oligodendrocytes and their precursors in vitro and in vivo. We also have reported that insulin-like growth factor-I (IGF-I) can protect cultured oligodendrocytes and their precursors from TNF-alpha-induced damage. In this study, we investigated whether IGF-I can protect oligodendrocytes and myelination from TNF-alpha-induced damage in vivo by cross-breeding TNF-alpha transgenic (Tg) mice with IGF-I Tg mice that overexpress IGF-I exclusively in brain. At 8 weeks of age, compared with those of wild-type (WT) mice, the brain weights of TNF-alpha Tg mice were decreased by approximately 20%, and those of IGF-I Tg mice were increased by approximately 20%. The brain weights of mice that carry both TNF-alpha and IGF-I transgenes (TNF-alpha/IGF-I Tg mice) did not differ from those of WT mice. As judged by histochemical staining and immunostaining, myelin content in the cerebellum of TNF-alpha/IGF-I Tg mice was similar to that in WT mice and much more than that in TNF-alpha Tg mice. Consistently, Western immunoblot analysis showed that myelin basic protein (MBP) abundance in the cerebellum of TNF-alpha/IGF-I Tg mice was double that in TNF alpha Tg mice. In comparison with WT mice, the number of oligodendrocytes was decreased by approximately 36% in TNF-alpha Tg mice, whereas it was increased in IGF-I Tg mice by approximately 40%. Oligodendrocyte number in TNF-alpha/IGF-I Tg mice was almost twice that in TNF-alpha Tg mice. Furthermore, IGF-I overexpression significantly reduced TNF-alpha-induced increases in apoptotic cell number, active caspase-3 abundance, and degradaion of MBP. Our results indicate that IGF-I is capable of protecting myelin and oligodendrocytes from TNF alpha-induced damage in vivo. PMID- 17279556 TI - Changes in T-type calcium channel and its subtypes in overactive detrusor of the rats with partial bladder outflow obstruction. AB - AIMS: To investigate the activity of the T-type calcium channel (TCC) and the expression of its subtypes in overactive detrusor (OD) myocytes in rats after partial bladder outflow obstruction (PBOO). METHODS: Thirteen male Wistar rats with OD after PBOO (OD group) and eight sham-operated rats (control group) were studied. The two groups were compared regarding the expression of TCC subtype genes by reverse transcription-polymerase chain reaction (RT-PCR) and the TCC kinetics and cell action potential by whole-cell patch-clamp. RESULTS: The time course and density of the current were significantly higher in the OD cells than those in the control detrusor. Whole-cell patch-clamp analysis showed that the activation of TCCs in detrusor myocytes in the OD group was faster than the control group, but inactivation was almost the same in both groups, suggesting a significant enhancement of the Ca(2+) "window" current in the OD group. Patch clamp recording of action potentials in the OD cells indicated an increase in excitability and a decrease in the repolarization interval. RT-PCR assay showed an abnormal expression of alpha1G subtype in the OD cells. CONCLUSIONS: TCCs could be one of the crucial factors for the abnormal excitation in OD cells. The development of OD after PBOO presumably relates to the increase in TCC current in the bladder cells, the enhancement of the Ca(2+) "window" current for Ca(2+) inflow, the prolongation of the intracellular calcium oscillations, and the acceleration of the cell depolarization. PMID- 17279557 TI - Are they different, the same, or is one no worse and does it make a clinical difference? PMID- 17279558 TI - Electrical stimulation of sacral dermatomes in multiple sclerosis patients with neurogenic detrusor overactivity. AB - AIMS: Transcutaneous electrical stimulation of the dorsal penile/clitoral nerve (DPN) has been shown to suppress detrusor contractions in patients with neurogenic detrusor overactivity (NDO). However, the long-term use of surface electrodes in the genital region may not be well tolerated and may introduce hygienic challenges. The aim of this study was to assess whether electrical stimulation of the sacral dermatomes could suppress detrusor contractions in multiple sclerosis (MS) patients with NDO, hereby providing an alternative to DPN stimulation. MATERIALS AND METHODS: A total of 14 MS patients (8 M, 6 F) with low bladder capacity (<300 ml) and a recent urodynamic study showing detrusor overactivity incontinence participated in the study. Three successive slow fill cystometries (16 ml/min) were carried out in each patient. The first filling served as control filling where no stimulation was applied. In the second and third filling electrical stimulation of either the DPN or sacral dermatomes was applied automatically whenever the detrusor pressure exceeded 10 cmH2O. RESULTS: The control filling showed detrusor overactivity in 12 of the 14 patients. In 10 of the 12 patients one or more detrusor contractions could be suppressed with DPN stimulation. Electrical stimulation of the sacral dermatomes failed to suppress detrusor contractions in all patients. CONCLUSIONS: Although therapeutic effects may be present from stimulation of the sacral dermatomes, we were unable to demonstrate any acute effects during urodynamics. For this reason stimulation of the sacral dermatomes is not an option in a system that relies on the acute suppression of a detrusor contraction. PMID- 17279559 TI - How to make your article more acceptable for the statistical reviewer. AB - Many medical articles have problems with methodological aspects. To help prevent this, medical statisticians should be more involved in all aspects of medical research. Having more statistical reviewing of manuscripts submitted to journals should also help, but will not cure the problem. This paper makes some suggestions that may help authors make manuscripts more acceptable methodologically, but there is no substitute for statistical involvement throughout the research process. Neurourol. Urodynam. 26:318-322, 2007. (c) 2007 Wiley-Liss, Inc. PMID- 17279560 TI - Postural response of the pelvic floor and abdominal muscles in women with and without incontinence. AB - AIMS: To determine whether activity of the pelvic floor (PF) and abdominal muscles differs between continent and incontinent women in response to a postural perturbation with a moderately full or empty bladder. METHODS: Electromyographic (EMG) activity of the PF and abdominal muscles was recorded with surface electrodes prior to and after a postural perturbation in which a 1 kg weight was dropped 30 cm into a bucket held by the subject. Perturbations were applied to the trunk in trials in which the timing of the weight drop was unknown (unexpected) or predictable (expected). Trials were performed with the bladder empty, and when the subject reported a sensation of moderate bladder fullness after drinking between 200 and 1,000 ml of water. RESULTS: Women with incontinence demonstrated increased PF EMG compared to continent women both prior to and during the postural response associated with unexpected loading. In addition, obliquus externus abdominis EMG was increased in incontinent women during these trials. When the bladder was moderately full, PF EMG decreased, whereas abdominal muscle EMG tended to increase. CONCLUSIONS: These data suggest that women with incontinence have increased PF and abdominal muscle activity associated with postural perturbations. This finding challenges the clinical assumption that incontinence is associated with reduced PF muscle activity, and suggests that training control and coordination of abdominal muscle activity may be important in treatment of this condition. The contrasting effects of increased bladder volume on PF and abdominal muscle EMG are likely to present further challenges to the maintenance of continence. PMID- 17279561 TI - Combined serial section-based 3D reconstruction of cervical carcinoma invasion using H&E/p16INK4a/CD3 alternate staining. AB - BACKGROUND: Malignant growth and invasiveness of cancers is a function of both intratumoral and stromal factors. The accessibility to nutrients, oxygen and growth factors, the stromal composition, and the interference with the immune system all shape the tumor invasion front. A recent study has shown a prognostic difference with respect to different invasion patterns analyzed on histological specimens of cervical cancers. The present study analyzes the spatial organization of a cervical cancer and the relation of the tumor invasion front and the infiltration with CD3(+) T-cells. METHODS: From a cervical squamous cell carcinoma specimen, 84 serial sections were performed and three interleaving series were stained with hematoxylin/eosin and immunohistochemistry directed against the cervical carcinoma biomarker p16(INK4a) and the T-cell marker CD3. Sections were passed through an image processing chain to obtain a reconstructed and segmented tissue volume. For local tumor invasion front analysis the mean curvature was used, which in turn was related to the respective local minimum tumor to T-cell distance as well to a T-cell originated diffusing substance's concentration at the tumor surface. RESULTS: Spatial models of the tumor tissue and the infiltrating T-cells were computed. The overall discrete compactness of the tumor invasion front was 0.89, corresponding to a pathological assessment of diffuse infiltration. The comparison of the tumor invasion front with the density of T-cell infiltration revealed an increased smoothening in regions with high T cell infiltration. CONCLUSIONS: We could demonstrate the spatial organization of a cervical cancer and model the interaction between infiltrating T-cells with the tumor invasion front shape. Increased smoothening in regions with high T-cell infiltration suggests that T-cells may have an influence on the shaping of the tumor invasion front, e.g., by attacking tumor cells displaying specific antigens. The applied technique allows visualization of the spatial organization of tissues and could be extended to analyze multiple stains on alternating sections. PMID- 17279562 TI - CaTiO(3) coating on titanium for biomaterial application--optimum thickness and tissue response. AB - The objectives of this study were to determine the optimum thickness of a CaTiO(3) film for biomaterial applications and to investigate the biocompatibility and bone formation of titanium with a CaTiO(3) film. First, CaTiO(3) films of 10, 20, 30, and 50 nm in thickness were deposited on titanium substrates using radiofrequency magnetron sputtering followed by annealing at 873 K in air for 7.2 ks. The optimum thickness of the CaTiO(3) film for bone formation was determined by comparison with its performance regarding calcium phosphate formation in Hanks' balanced saline solution (HBSS). Regarding calcium phosphate formation, the performance of the specimen with a 50-nm-thick CaTiO(3) film was superior to those of specimens with other thicknesses. A titanium prism with a CaTiO(3) film of 50-nm in thickness was surgically inserted in both soft and hard rat tissues. The biocompatibility of CaTiO(3)-deposited titanium and bone formation on it was investigated by histological observations. A slight inflammatory reaction was observed around the titanium with the 50-nm-thick CaTiO(3) film, while no severe response, such as degeneration and necrosis, was observed in either soft or hard rat tissue. New bone formation on the titanium plate with the CaTiO(3) film was more active than that without the film. The 50 nm-thick CaTiO(3) film has biocompatibility and can facilitate new bone formation in vivo, and, consequently, it is an excellent surface modification method for biomaterial applications. PMID- 17279563 TI - Bone tissue engineering with human mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force. AB - An in vitro reconstruction of three-dimensional (3D) tissues without the use of scaffolds may be an alternative strategy for tissue engineering. We have developed a novel tissue engineering strategy, termed magnetic force-based tissue engineering (Mag-TE), in which magnetite cationic liposomes (MCLs) with a positive charge at the liposomal surface, and magnetic force were used to construct 3D tissue without scaffolds. In this study, human mesenchymal stem cells (MSCs) magnetically labeled with MCLs were seeded onto an ultra-low attachment culture surface, and a magnet (4000 G) was placed on the reverse side. The MSCs formed multilayered sheet-like structures after a 24-h culture period. MSCs in the sheets constructed by Mag-TE maintained an in vitro ability to differentiate into osteoblasts, adipocytes, or chondrocytes after a 21-day culture period using each induction medium. Using an electromagnet, MSC sheets constructed by Mag-TE were harvested and transplanted into the bone defect in the crania of nude rats. Histological observation revealed that new bone surrounded by osteoblast-like cells was formed in the defect area 14 days after transplantation with MSC sheets, whereas no bone formation was observed in control rats without the transplant. These results indicated that Mag-TE could be used for the transplantation of MSC sheets using magnetite nanoparticles and magnetic force, providing novel methodology for bone tissue engineering. PMID- 17279564 TI - Chitosan-phosphorylated chitosan polyelectrolyte complex hydrogel as an osteoblast carrier. AB - To simulate extra-cellular matrix, a novel three-dimensional scaffold of polyelectrolyte complex (PEC) hydrogel as an osteoblast carrier was synthesized. First, chitosan, a natural glycosaminoglycan, was modified by phosphorylation to obtain a water-soluble phosphorylated chitosan (P-content: 10.7 mass%). The PEC hydrogel was then formed from equal volumes of 0.173 mass% phosphorylated chitosan in water and 1 mass% chitosan in 1% (V/V) acetic acid solution. Rat osteoblasts were seeded in the hydrogel. The PEC hydrogel had a three-dimensional hierarchically-porous structure and good cytobiocompatibility for osteoblasts in vitro. It is concluded that the PEC hydrogel is a promising material as an osteoblast carrier. PMID- 17279565 TI - Injectable nanocrystalline hydroxyapatite paste for bone substitution: in vivo analysis of biocompatibility and vascularization. AB - The nanocrystalline hydroxyapatite paste Ostim represents a fully degradable synthetic bone substitute for the filling of bone defects. Herein, we investigated in vivo the inflammatory and angiogenic host tissue response to this biomaterial after implantation. For this purpose, Ostim was implanted into the dorsal skinfold chambers of Syrian golden hamsters. The hydroxyapatite ceramic Cerabone and isogeneic transplanted cancellous bone served as controls. Angiogenesis, microhemodynamics, microvascular permeability, and leukocyte endothelial cell interaction of the host tissue were analyzed over 2 weeks using intravital fluorescence microscopy. Ostim exhibited good biocompatibility comparable to that of Cerabone and cancellous bone, as indicated by a lack of venular leukocyte activation after implantation. Cancellous bone induced a more pronounced angiogenic response and an increased microvessel density when compared with the synthetic bone substitutes. In contrast to Cerabone, however, Ostim showed a guided neovascularization directed toward areas of degradation. Histology confirmed the ingrowth of proliferating vascularized tissue into the hydroxyapatite paste at sites of degradation, while the hydroxyapatite ceramic was not pierced by new microvessels. Thus, Ostim represents an injectable synthetic bone substitute, which may optimize the conditions for the formation of new bone at sites of bone defects by supporting a guided vascularization during biodegradation. PMID- 17279566 TI - Preparation of porous collagen/hyaluronic acid hybrid scaffolds for biomimetic functionalization through biochemical binding affinity. AB - This study demonstrated the feasibility of introducing an avidin-biotin system to three-dimensional and highly porous scaffolds for the purpose of designing scaffolds that have binding affinity with bioactive molecules for various biomimetic modifications. Porous hybrid scaffolds composed of collagen and hyaluronic acid (HA) were prepared by a novel overrun process. The overrun processed scaffolds showed a uniform dual-pore structure because of the injection of gas bubbles and ice recrystallization during the fabrication process and had a higher porosity than scaffolds prepared by a conventional freeze-drying method. The mechanical strength and biodegradation kinetics were controlled by the method of preparation and the composition of collagen/HA. Collagen/HA scaffolds did not show any significant adverse effects on cell viability even after 10 days of incubation. The fibroblasts cultured in the overrun-processed scaffolds were widely distributed and had proliferated on the surfaces of the macropores in the scaffolds, whereas the cells that were seeded in the freeze-dried scaffolds had attached mainly on the dense surface of the scaffolds. As the collagen content in the scaffolds increased, the cellular ingrowth into the inner pores of the scaffolds decreased because of the high affinity between the collagen and the cells. Measurements obtained via confocal microscopy revealed that the porous collagen/HA scaffolds could be functionalized with the biotin by incorporating avidin. Therefore, the present biotinylation approach may allow the incorporation of various bioactive molecules (DNA, growth factors, drug, peptide, etc) into the three-dimensional porous scaffolds. PMID- 17279567 TI - Factors related to contraction and mechanical strength of collagen gels seeded with canine endotenon cells. AB - Fibroblasts can construct a hydrated collagen lattice to a tissue-like structure that is greatly influenced by initial culture conditions. The purpose of this study was to investigate the effects of cell concentration and collagen concentration on the contraction kinetics and mechanical properties of resultant endotenon-derived fibroblast-seeded collagen lattice. The experiment was designed to evaluate the effect of cell concentration (0, 0.25, 0.5, and 1.0 x10(6) cells/mL) and collagen concentration (0.5, 1.0, 1.5, and 2.0 mg/mL). Collagen lattice contraction was recorded for 42 days, after which time the lattices were mechanically tested. The collagen lattices seeded with higher initial cell concentration had a shorter contraction lag phase (p < 0.01), and exhibited a higher ultimate stress (p < 0.01) and instantaneous and equilibrium modulus (p < 0.01) than those seeded with a lower initial cell concentration. The collagen lattices cultured with a lower initial collagen concentration also had a shorter contraction lag phase, and exhibited greater instantaneous and equilibrium modulus (p < 0.01) than those cultured with higher initial collagen concentration. The collagen lattices of initial 0.5 mg/mL collagen concentration had the highest value of ultimate stress (p < 0.03). PMID- 17279568 TI - Quantum Dots as alternatives to organic fluorophores for Cryptosporidium detection using conventional flow cytometry and specific monoclonal antibodies: lessons learned. AB - BACKGROUND: Significant developments in biological applications are occurring through the incorporation of Quantum Dots (QDs) as biological labels. The demonstration of QDs unique optical properties may have important implications for the study of environmental samples, where microorganisms of interest need to be isolated away from the background debris. METHODS: Flow cytometric analysis was used to determine the fluorescence intensity of oocysts after mAb staining by QDs or organic fluorophore conjugates. In addition, the level of non-specific binding to detrital particles within a control water concentrate was estimated using the optimal staining concentration determined for each mAb analyzed. RESULTS: Under 488 nm excitation, oocysts stained with QD-conjugates exhibited significantly lower fluorescence intensity than organic conjugates. Moreover, the level of non-specific binding by QD-conjugates to detrital particles present in the water concentrate was significantly higher that of the organic conjugates. CONCLUSIONS: While QDs are noted for their superior spectral characteristics, they have been shown here to be unsuitable for conventional flow cytometric detection of Cryptosporidium. Therefore, we conclude that in their current form, QD's are severely limited for fluorescent detection of pathogens in environmental applications. PMID- 17279569 TI - Development and validation of flow cytometric measurement for parasitemia in cultures of P. falciparum vitally stained with YOYO-1. AB - BACKGROUND: The need for improved malaria diagnostics has long been recognized. METHODS: Human parasitized erythrocytes based on the principles of flow cytometry (FCM) method is described for the determination of parasitemia in Plasmodium falciparum cultures using the fluorescence activated cell sorter and DNA-binding fluorescent dye, YOYO-1. The same assay samples can be also evaluated both microscopically and by scintillation counting after use of (3)H-hypoxanthine labeled parasites. RESULTS: The counts of uninfected, infected, and nucleated cells occurred with high precision. The cells were categorized into different populations according to their physical or chemical properties such as RNase treatment and compensation required optimization. The detection and quantitation limits in the assay were 0.003% and 0.008% parasitemia, respectively. Overall, the parasite counts by FCM measurement correlated highly (r(2) = 0.923-0.968) with the parasitemia measured by (3)H-hypoxanthine incorporation assay when parasites variants incubated with various antimalarial drugs. In addition, the low levels of parasitemia (7.9%-21.3%) detected by microscopy than by FCM may be related to a number of tiny schizonts externally attached to the erythrocyte membranes but were not definitely inside the erythrocyte that normally would never be included in microscopy counting. CONCLUSION: On the basis of data reported herein, a rapid, high sensitivity, lower sampling error and reliable identification of human parasitized erythrocytes by the principles of FCM have been established. Published 2007 Wiley-Liss, Inc. PMID- 17279570 TI - Comparative study between two laser scanning cytometers and epifluorescence microscopy for the detection of Cryptosporidium oocysts in water. AB - BACKGROUND: Cryptosporidium detection in water and environmental samples has increased during the last years, largely due to an increase in the number of reported waterborne outbreaks of cryptosporidiosis and the implementation of new regulations about Cryptosporidium monitoring in water supplies. The aim of this study was to validate and compare the capacity of two laser scanning cytometers commercially available (LSC and ChemScanRDI), against manual microscopic enumeration of Cryptosporidium oocysts in surface water and reference material samples. METHODS: Reference material and surface water samples were analysed by two laser scanning cytometers methodologies and by manual epifluorescence microscopy. Two mAbs from commercial suppliers were used to evaluate background reduction. RESULTS: Highly significant correlations were obtain between both cytometers (R(2) = 0.99) and with manual microscopy (R(2) = 0.98), showing that oocysts counts made by cytometers were equivalent to those obtained with conventional methods. We observed a variability in oocysts counts when different antibodies where used with laser scanning cytometers and manual microscopy. CONCLUSIONS: This study showed the efficacy of the laser scanning technology (LSC and ChemScanRDI), as an automated and a more standardized alternative to manual epifluorescence microscopy examination, for Cryptosporidium detection in water samples. High quality antibodies are needed for automated enumeration as well as for manual microscope observations. PMID- 17279571 TI - Extended depth of field imaging for high speed cell analysis. AB - BACKGROUND: Fluoresence microscopy is an extremely useful tool to analyze the intensity, location and movement of fluorescently tagged molecules on, within or between cells. However, the technique suffers from slow image acquisition rates and limited depth of field. Confocal microscopy addresses the depth of field issue via "optical sectioning and reconstruction", but only by further reducing the image acquisition rate to repeatedly scan the cell at multiple focal planes. In this paper we describe a technique to perform high speed, extended depth of field (EDF) imaging using a modified ImageStream system whereby high resolution, multimode imagery from thousands of cells is collected in less than a minute with focus maintained over a 16 microm focal range. METHODS: A prototype EDF ImageStream system incorporating a Wavefront Coded element was used to capture imagery from fluorescently labeled beads. Bead imagery was quantitatively analyzed using photometric and morphological features to assess consistency of feature values with respect to focus position. Jurkat cells probed for chromosome Y using a fluorescence in situ hybridization in suspension protocol (FISHIS) were used to compare standard and Wavefront Coded-based EDF imaging approaches for automated chromosome enumeration. RESULTS: Qualitative visual inspection of bead imagery reveals that the prototype ImageStream system with EDF maintains focus quality over a 16 microm focus range. Quantitative analysis shows the extended depth field collection mode has approximately ten-fold less variation in focus sensitive feature values when compared with standard imaging. Automated chromosome enumeration from imagery of Jurkat cells probed using the FISHIS protocol is significantly more accurate using EDF imaging. CONCLUSIONS: The use of EDF techniques may significantly enhance the quantitation of cell imagery, particularly in applications such as FISH, where small discrete signals must be detected over a wide focal range within the cell. PMID- 17279573 TI - Combination of quantification and observation methods for study of "Side Population" cells in their "in vitro" microenvironment. AB - BACKGROUND: Qualitative and quantitative analyses of the rare phenotypic variants in in vitro culture systems is necessary for the understanding of cell differentiation in cell culture of primary cells or cell lines. Slide-based cytometry combines image acquisition and data treatment, and associates the power of flow cytometry (FCM) and the resolution of the microscopic studies making it suitable for the analysis of cells with rare phenotype. In this paper we develop a method that applies these principles to a particularly hot problem in cell biology, the study of stem cell like cells in cultures of primary cells, cancer cells, and various cell lines. METHODS: The adherent cells were labeled by the fluorescent dye Hoechst 33342. The images of cell populations were collected by a two-photon microscope and processed by a software developed by us. The software allows the automated segmentation of the nuclei in a very dense cell environment, the measurement of the fluorescence intensity of each nucleus and the recording of their position in the plate. The cells with a given fluorescence intensity can then be located easily on the recorded image of the culture plate for further analysis. RESULTS: The potential of our method is illustrated by the identification and localization of SP cells in the cultures of the C2C12 cell line. Although these cells represent only about 1% of the total population as calculated by flow cytometry, they can be identified in the culture plate with high precision by microscopy. CONCLUSION: Cells with the rare stem-cell like phenotype can be efficiently identified in the undisturbed cultures. Since the fluorescence intensity of rare events and the position of thousands of surrounding cells are recorded at the same time, the method associates the advantage of the FCM analysis and the microscopic observation. PMID- 17279572 TI - Developmental expression of FOG-1/CPEB protein and its control in the Caenorhabditis elegans hermaphrodite germ line. AB - The specification of a germ cell as sperm or oocyte and determination of cell number remain unsolved questions in developmental biology. This paper examines Caenorhabditis elegans FOG-1, a CPEB-related RNA-binding protein that controls the sperm fate. We find that abundant FOG-1 protein is observed transiently in germ cells just prior to their expression of an early sperm-differentiation marker. As the germline tissue elongates, abundant FOG-1 appears more and more distally as sperm become specified, but disappears when the germ line switches to oogenesis. This dynamic pattern is controlled by both globally acting and germline-specific sex-determining regulators. Importantly, the extent of FOG-1 expression corresponds roughly to sperm number in wild-type and mutants, altering sperm number. By contrast, three other key regulators of the sperm/oocyte decision do not similarly correspond to sperm number. We suggest that FOG-1 is precisely modulated in both time and space to specify sperm fate and control sperm number. PMID- 17279574 TI - Genistein prevents thyroid hormone-dependent tail regression of Rana catesbeiana tadpoles by targetting protein kinase C and thyroid hormone receptor alpha. AB - Thyroid hormone (TH)-regulated gene expression is mainly mediated by TH binding to nuclear thyroid hormone receptors (TRs). Despite extensive studies in mammalian cell lines that show that phosphorylation signaling pathways are important in TH action, little is known about their roles on TH signaling in vivo during development. Anuran metamorphosis is a postembryonic process that is absolutely dependent upon TH and tadpole tail resorption can be precociously induced by exogenous administration of 3,5,3'-triiodothyronine (T(3)). We demonstrate that genistein (a major isoflavone in soy products and tyrosine kinase inhibitor) and the PKC inhibitor (H7) prevent T(3)-induced regression of the Rana catesbeiana tadpole tail. T(3)-induced protein kinase C tyrosine phosphorylation and kinase activity are inhibited by genistein while T(3)-induced up-regulation of TRbeta mRNA, but not TRalpha mRNA, is significantly attenuated, most likely through inhibition of T(3)-dependent phosphorylation of the TRalpha protein. This phosphorylation may be modulated through PKC. These data demonstrate that T(3) signaling in the context of normal cells in vivo includes phosphorylation as an important factor in establishing T(3)-dependent tail regression during development. PMID- 17279575 TI - Cadherin-4 plays a role in the development of zebrafish cranial ganglia and lateral line system. AB - We previously reported that cadherin-4 (also called R-cadherin) was expressed by the majority of the developing zebrafish cranial and lateral line ganglia. Cadherin-4 (Cdh4) function in the formation of these structures in zebrafish was studied using morpholino antisense technology. Differentiation of the cranial and lateral line ganglia and lateral line nerve and neuromasts of the cdh4 morphants was analyzed using multiple neural markers. We found that a subset of the morphant cranial and lateral line ganglia were disorganized, smaller, with reduced staining, and/or with altered shape compared to control embryos. Increased cell death in the morphant ganglia likely contributed to these defects. Moreover, cdh4 morphants had shorter lateral line nerves and a reduced number of neuromasts, which was likely caused by disrupted migration of the lateral line primordia. These results indicate that Cdh4 plays a role in the normal formation of the zebrafish lateral line system and a subset of the cranial ganglia. PMID- 17279576 TI - Visualization of two distinct classes of neurons by gad2 and zic1 promoter/enhancer elements in the dorsal hindbrain of developing zebrafish reveals neuronal connectivity related to the auditory and lateral line systems. AB - The dorsal hindbrain includes distinct classes of neurons for processing various sensory stimuli, but the developmental aspects of these neurons remain largely unknown. We identify here two distinct classes of neurons in the dorsal hindbrain of developing zebrafish: (1) neurons that express the inhibitory neuronal marker Gad1/2, and (2) neurons that express the zn-5 antigen and Lhx2/9 and require the basic helix-loop-helix transcription factor Atoh1a for development. Neurons were traced to their axon terminals by expressing green fluorescent protein using the Gal4VP16-UAS (UAS, upstream activating sequences) system in combination with the promoter/enhancer regions of gad2 for the Gad1/2(+) neurons and zic1 for the zn 5(+)Lhx2/9(+) neurons. The Gad1/2(+) neurons projected to the contralateral hindbrain, while the zn-5(+)Lhx2/9(+) neurons projected to the contralateral midbrain torus semicircularis, suggesting a role in auditory and lateral line sensory processing. Comparison of these projections with those from the cochlear nuclei to the inferior colliculus in mammals suggests similarities across vertebrate species. PMID- 17279577 TI - Dermal condensation formation in the chick embryo: requirement for integrin engagement and subsequent stabilization by a possible notch/integrin interaction. AB - During embryonic development, feathers appear first as primordia consisting of an epidermal placode associated with a dermal condensation. When 7-day chick embryo dorsal skin fragments showing three rows of feather primordia are cultured, they undergo a complete reorganization, which involves the down-regulation of morphogenetic genes and dispersal of dermal fibroblasts, leading to the disappearance of primordia. This loss of organisation is followed by de novo differentiation events. We have used this model to study potential factors involved in the formation of dermal condensations. Activation of Integrins by extracellular Manganese or intracellular Calcium prevents the initial disappearance of the dermal condensations. New primordia formation occurs even after inhibition of the Notch pathway albeit with some fusion between primordia. In conclusion, dermal fibroblast migration requires beta1-Integrin whereas the stability of dermal condensations could depend on Notch/Integrin interaction. PMID- 17279578 TI - What is the role of adjuvant radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion? AB - BACKGROUND: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) is infrequent, occurring in 2.5% to 14% of patients, but it is important prognostically, because it carries an increased risk of recurrence and metastasis. Although both excision and Mohs micrographic surgery (MMS) are used to treat SCC with PNI, postoperative radiation therapy (XRT) often is recommended to minimize the risk of recurrence. To date, the effectiveness of adjuvant XRT in this setting has not been determined definitively. METHODS: The authors evaluated the effectiveness of adjuvant XRT in treating SCC with PNI by performing a thorough literature review. RESULTS: For SCC with PNI, the local control rate after MMS with or without XRT was from 92% to 100% compared with a control rate from 38% to 100% after standard excision with or without XRT. A better prognosis was associated with negative pretreatment magnetic resonance imaging or computed tomography findings than with positive radiographic evidence of PNI. Primary SCC with PNI was associated with better local control than recurrent SCC with PNI. When treatment outcomes were stratified by PNI type, SCC with microscopic PNI and SCC with extensive PNI had local control rates from 78% to 87% and from 50% to 55%, respectively. Adjuvant XRT was associated in selected patients with 100% local control. CONCLUSIONS: Few studies addressed the effectiveness of adjuvant XRT in patients who have SCC with PNI. Although XRT has been established as an adjuvant treatment for selected patients, the extent of nerve involvement by tumor, particularly in the setting of other high-risk features, may be helpful in defining its role. In the future, a multicentered, prospective, randomized clinical trial will be needed to assess the true efficacy of adjuvant XRT in the treatment of patients with SCC and PNI. PMID- 17279579 TI - Patients with differentiated thyroid cancer have a venous gradient in thyroglobulin levels. AB - BACKGROUND: Although serum thyroglobulin (Tg) is an excellent marker for detecting recurrent or persistent differentiated thyroid cancer (DTC), it is unreliable in patients who have positive anti-Tg antibodies. Furthermore, a growing number of patients with DTC have elevated Tg levels but no detectable disease on radioiodine scanning or other imaging studies. The objective of this study was to determine whether a gradient in Tg protein level exists in patients with DTC. METHODS: Fifteen patients who underwent thyroidectomy and/or lymph node dissection for primary DTC (n = 10 patients) and recurrent or persistent DTC (n = 5 patients). A venipuncture was performed simultaneously from the internal jugular vein adjacent to the tumor and the ipsilateral antecubital vein. Venous Tg protein levels were measured by using a chemiluminescence assay. RESULTS.: The average internal jugular-to-antecubital vein Tg protein ratio was 3.4:1.0 (median Tg ratio, 2.9:1; range, 0.8-62.2). Four patients had positive anti-Tg antibodies but still had a Tg gradient. Tg levels were significantly higher in the adjacent internal jugular vein than in the antecubital vein (P = .0019). The Tg ratio between the internal jugular and antecubital veins was significantly higher in patients with recurrent or persistent DTC than in patients with primary tumors (P = .0196). CONCLUSIONS: To the authors' knowledge, this is the first study to document a venous gradient in Tg protein levels in patients with DTC. The findings suggested that venous sampling for Tg may be used to localize DTC in some patients who have high or increasing serum Tg levels but negative radioiodine scans or imaging studies. PMID- 17279580 TI - Therapy for elderly patients with acute myeloid leukemia: a problem in search of solutions. PMID- 17279581 TI - Noninvasive imaging for evaluation of the systemic delivery of capsid-modified adenovirus in an orthotopic model of advanced lung cancer. PMID- 17279582 TI - Thalidomide therapy in adult patients with myelodysplastic syndrome: a north central cancer treatment group phase II trial. PMID- 17279584 TI - Novel marker D2-40, combined with calretinin, CEA, and TTF-1: an optimal set of immunodiagnostic markers for pleural mesothelioma. AB - BACKGROUND: Malignant pleural mesothelioma is a challenging disease with regard to diagnosis and treatment; early and accurate diagnosis would lead to appropriate therapeutic strategies, including extrapleural pneumonectomy. Immunohistochemistry has proven valuable for the diagnosis of the most common epithelioid mesothelioma, although it is often difficult to differentiate it from pulmonary or metastatic adenocarcinoma with absolute certainty if a single antibody is employed. The current study was designed to identify an immunodiagnostic panel for pleural mesothelioma. METHODS: Large surgical specimens from 66 cases with pleural mesothelioma and 66 with lung adenocarcinoma were immunohistochemically reevaluated under uniform conditions. The antibodies examined were directed against the novel mesothelial marker D2-40, as well as calretinin, CEA, and TTF-1. RESULTS: For mesothelioma the sensitivities of D2-40 and calretinin were 84.8% and 87.9%, respectively, and their specificities were both 95.5%. For adenocarcinoma, the sensitivities of CEA and TTF-1 were 95.5% and 92.4%, respectively, and their specificities were both 100%. Immunoreactivity to D2-40 and calretinin was observed in most areas of epithelioid differentiation in mesothelioma. Western blots also showed higher levels of D2-40 antigen in pleura invaded by epithelioid mesothelioma as compared with unaffected pleura. CONCLUSIONS: These data strongly suggest the significant usefulness of D2-40 and calretinin as positive markers, and of CEA and TTF-1 as negative markers, for pleural mesothelioma. The 4-antibody immunohistochemical panel showed high sensitivity and specificity with regard to differentiation of epithelioid mesothelioma from lung adenocarcinoma. PMID- 17279586 TI - Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules. AB - BACKGROUND: Stromal invasion is 1 of the main features used to distinguish high grade dysplastic nodules (DNs) from well-differentiated hepatocellular carcinomas (HCCs). The authors hypothesized that ductular reaction (DR) takes place around noninvasive hepatocellular nodules but not within the stroma contiguous to invasive HCC. METHODS: DR/cytokeratin 7 (CK7)-positive patterns were evaluated in 105 resected small hepatic nodules according to the level of invasion. The nodules were classified histologically prior to immunostaining as noninvasive (large regenerative nodules, low-grade DNs, and high-grade DNs), minimally invasive (early HCCs with a vaguely nodular type), and overtly invasive (typical HCCs with a distinctly nodular type) in a review by expert pathologists, the current gold standard. Intranodular DR (inner DR) and DR around the nodule periphery (outer DR) were assessed separately on a semiquantitative scale from 0 to 4+. RESULTS: DR was 3 or 4+ in the majority of noninvasive nodules (inner DR, 81%; outer DR, 91%), whereas DR was 0 or 1+ in overtly invasive HCCs (inner DR, 96%; outer DR, 81%). Minimally invasive HCCs showed an intermediate DR pattern (2 or 3+ inner DR, 75%; 2+ outer DR, 67%). DR characteristically was absent at the stromal-invasive, leading edge of tumor cells in both minimally invasive HCCs (focal loss of DR/CK7) and overtly invasive HCCs (diffuse loss of DR/CK7). The DR patterns in 41 needle-biopsy samples were similar to the patterns observed in resected nodules. CONCLUSIONS: DR/CK7 immunostaining may help to identify small foci of invasion and to distinguish noninvasive, high-grade DNs from both minimally invasive and overtly invasive HCCs. PMID- 17279588 TI - Crystal structure of a spin-labeled, channel-forming alamethicin analogue. PMID- 17279585 TI - Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. AB - BACKGROUND: Approximately 30% to 40% of all patients with osteosarcomas ultimately experience recurrence. The study investigated the hypothesis that the resistance of osteosarcoma to chemotherapy may be related to the expression of a pregnane xenobiotic receptor (PXR) variant protein and its role as the major inducer of P450 3A4 in these tumors. METHODS: Polymerase chain reaction (PCR) and Western blot analysis were used to determine PXR mRNA and protein expression, respectively. Real-time PCR and CYP3A catalytic activity using 7-benzyl trifluoromethyl coumarin (BFC) as the probe substrate were used to measure the induction of P450 3A4 or MDR1. siRNA transfections were performed for PXR and cytotoxicity determined by a colorimetric based assay or Annexin v-Fitc staining. RESULTS: Differences were observed in the molecular size of the PXR protein expressed in sarcoma cell lines when compared with the wildtype PXR expressed in normal liver, kidney, or small intestine. A polyclonal PXR antibody raised against the N-terminus of the wildtype PXR did not detect PXR expressed in these sarcoma cell lines. In the osteosarcoma cell lines, etoposide and doxorubicin were better inducers of P450 3A4 and MDR1 than rifampin. siRNA against PXR down regulated P450 3A4 expression only in the osteosarcoma cell line. Cytotoxicity assays showed that the resistance of the osteosarcoma cell lines to etoposide correlated with PXR protein expression levels and activation of P450 3A4 and could be prevented by ketoconazole. CONCLUSION: The results suggest that PXR plays a critical role in the regulation of P450 3A4 expression in osteosarcoma and that its expression and activation in these tumors may influence the effect of chemotherapeutic agents on the induction of target genes implicated in drug resistance. PMID- 17279589 TI - Detecting force-induced molecular transitions with fluorescence resonant energy transfer. PMID- 17279591 TI - Bivalent peptides as models for multimeric targets of PDZ domains. AB - PDZ domains are among the most common modules in eukaryotic, including human, genomes. They are found exclusively in large, multidomain cytosolic proteins- often with other domains that belong to a variety of families--and are involved in a plethora of physiological and pathophysiological events. PDZ domains mediate protein-protein interactions by binding to solvent-exposed and extended C terminal short fragments of membrane-associated proteins, such as receptors and ion channels. Most of what is known about the mechanisms of target binding by PDZ domains is inferred from studies that involve isolated recombinant PDZ domains and short synthetic peptides that represent the targets. These binary systems constitute an obvious oversimplification and disregard factors such as noncanonical modes of binding and enhanced affinity due to multimeric interactions mediated by clusters and oligomers of PDZ-domain-containing proteins. We have tested whether the interaction between a dimeric form of PDZ domain that mimics a functional dimeric guanine nucleotide exchange factor, PDZ RhoGEF (PDZ-containing RhoA-specific guanine nucleotide exchange factor) or LARG (leukemia-associated RhoA specific guanine nucleotide exchange factor), and a bivalent peptide that mimics the dimer of the plexin B receptor, could enhance the interaction between the two moieties. Peptide dimerization was achieved by cross-linking the N-terminal ends of peptides attached to Wang resin with poly(ethylene glycol) spacers (30-45 Angstroms in length). The interaction of dimeric PDZ domains with dimeric peptides resulted in an up to 20-fold increase in affinity compared to the simple binary system. This is consistent with the notion that multimerization of both receptors and PDZ-containing proteins might constitute an important regulatory mechanism. PMID- 17279590 TI - Directed DNA polymerase evolution: effects of mutations in motif C on the mismatch-extension selectivity of thermus aquaticus DNA polymerase. AB - The selectivity of DNA polymerases for processing the canonical nucleotide and DNA substrate in favor of the noncanonical ones is the key to the integrity of the genome of every living species and to many biotechnological applications. The inborn ability of most DNA polymerases to abort efficient extension of mismatched DNA substrates adds to the overall DNA polymerase selectivity. DNA polymerases have been grouped into families according to their sequence. Within family A DNA polymerases, six motifs that come into contact with the substrates and form the active site have been discovered to be evolutionary highly conserved. Here we present results obtained from amino acid randomization within one motif, motif C, of thermostable Thermus aquaticus DNA polymerase. We have identified several distinct mutation patterns that increase the selectivity of mismatch extension. These results might lead to direct applications such as allele-specific PCR, as demonstrated by real-time PCR experiments and add to our understanding of DNA polymerase selectivity. PMID- 17279592 TI - Exploiting the substrate tolerance of farnesyltransferase for site-selective protein derivatization. AB - The site-selective modification of proteins with a functional group is an important biochemical technique, but covalent attachment of a desired group to a chosen site is complicated by the reactivity of other amino acid side chains, often resulting in undesired side reactions. One potential solution to this problem involves exploiting the activity of protein-modifying enzymes that recognize a defined protein sequence. Protein farnesyltransferase (FTase) covalently attaches an isoprenoid moiety to a cysteine unit in the context of a short C-terminal sequence that can be easily grafted onto recombinant proteins. Here we describe the synthesis of four phosphoisoprenoids functionalized with biotin, azide, or diene groups. These phosphoisoprenoids bound to FTase with affinities comparable to that of the native substrate. With the exception of the biotin-functionalized analogue, all the phosphoisoprenoids generated could be transferred to peptide and protein substrates by FTase. Unlike proteins modified with farnesyl moieties, Ypt7 prenylated with (2E,6E)-8-(azidoacetamido)-3,7 dimethylocta-2,6-dienyl groups did not oligomerize and showed no detectable increase in hydrophobicity. To assess the suitability of the functionalized isoprenoids for protein modifications they were further derivatized, both by Diels-Alder cycloaddition with 6-maleimidohexanoic acid and by Staudinger ligation with a phosphine. We demonstrate that the Staudinger ligation proceeds more rapidly and is more efficient than the Diels-Alder cycloaddition. Our data validate the use of FTase as a protein-modification tool for biochemical and biotechnological applications. PMID- 17279593 TI - Vinyl-pyridinium triphenylamines: novel far-red emitters with high photostability and two-photon absorption properties for staining DNA. AB - A series of mono-, bis- and trisvinyl-pyridinium triphenylamines (TP-py) has been synthesised and evaluated for its one- and two-photon absorption (2PA) induced fluorescence properties under biological conditions. Interestingly, these compounds are only weakly fluorescent in water, whereas their fluorescence emissions are strongly restored (exaltation factors of 20-100) upon binding to double-stranded DNA. Additional measurements in glycerol indicate that the fluorescence increases are the result of immobilisation of the dyes in the DNA matrix, which inhibits rotational de-excitation modes. This particular feature is especially remarkable in the case of the bis and tris derivatives (TP-2 py, TP-3 py), which each display a high affinity (K(d) ~ microM) for dsDNA. TPIF measurements have shown that TP-2 py and TP-3 py each have a large 2PA cross section (delta up to 700 GM) both in glycerol and in the presence of DNA, which ranks them amongst the best 2PA biological fluorophores. Finally, one- and two photon confocal imaging in cells revealed that these compounds perform red staining (lambda(em)=660-680 nm) of nuclear DNA with excellent contrast. The remarkable optical properties of the TP-py series, combined with their high photostability and their easy synthetic access, make these compounds extremely attractive for use in confocal and 2PA microscopy. PMID- 17279594 TI - Photophysics of eumelanin: ab initio studies on the electronic spectroscopy and photochemistry of 5,6-dihydroxyindole. AB - Excited-state reaction paths and energy profiles of 5,6-dihydroxyindole (DHI), one of the elementary building blocks of eumelanin, have been determined with the approximated singles-and-doubles coupled-cluster (CC2) method. 6-Hydroxy-4 dihydro-indol-5-one (HHI) is identified as a photochromic species, which is formed via nonadiabatic hydrogen migration from the dangling OH group of DHI to the neighboring carbon atom of the six-membered ring. It is shown that HHI is a typical excited-state hydrogen-transfer (ESIHT) system. HHI absorbs strongly in the visible range of the spectrum. A barrierless hydrogen transfer in the (1)pipi* excited state, followed by barrierless torsion of the hydroxyl group, lead to a low-lying S(1)-S(0) conical intersection and thus to ultrafast internal conversion. This very efficient mechanism of excited-state deactivation provides HHI with a high degree of intrinsic photostability. It is suggested that the metastable photochemical product HHI plays an essential role for the photoprotective biological function of eumelanin. PMID- 17279595 TI - Characterization of phenolic compounds in the fruits of Forsythia suspensa by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. AB - Phenolic compounds are the major bioactive constituents of Forsythia suspensa, an important Chinese herbal medicine used for the treatment of various infectious diseases. Fragmentation behaviors of the phenolic compounds in F. suspensa were investigated by using a high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS(n)) method. For common phenylethanoid glycosides, the loss of the caffeoyl moiety was the first fragmentation step, then sequential losses of rhamnose, hexose and water were observed in further fragmentations. If a substituent group presented in the beta position, the fragmentation was triggered by initial loss of a substituent group to form structures such as suspensaside A. Then it underwent the common fragmentation pathways as mentioned above, or eliminated characteristic residues of masses 134 or 152 Da, respectively. The latter pathway is reported here for the first time. The fragmentation behaviors of furofuran lignans displayed a typical cleavage of the tetrahydrofuran ring. However, the presence of a hydroxyl group at C-1 led to the successive loss of 30 Da. Neutral loss of CO(2) and benzyl cleavage were characteristic for lignans with a 2,3-dibenzylbutyrolactone skeleton. A neutral loss of 30 Da was also observed in the fragmentation pattern of flavonols. These fragmentation rules were implemented to analyze phenolic compounds in the fruits of F. suspensa. A total of 51 compounds, including 24 phenylethanoid glycosides, 21 lignans and 6 flavonols, were identified or tentatively characterized based on their retention times, UV spectra and MS fragmentation patterns. PMID- 17279596 TI - Concurrent quantification of light and heavy sulphur volatiles in wine by headspace solid-phase microextraction coupled with gas chromatography/mass spectrometry. AB - A new method based on headspace solid-phase microextraction coupled with gas chromatography/mass spectrometry (HS-SPME-GC/MS) to analyse 13 light and heavy volatile sulphur compounds in the same run was established. For the successful application of the procedure, various adsorption process parameters were optimised. In particular the nature of the adsorptive phase, the temperature, the ionic strength of the sample solutions and the equilibration time were considered. The best extraction conditions, in terms of the maximum signal obtainable for each compound, were obtained with a carboxen-polydimethylsiloxane divinylbenzene (CAR-PDMS-DVB) 2 cm long coating fibre. The choice of suitable internal standards and the matrix effect were studied and the proposed method was validated by determining linearity, precision and accuracy, evaluating the critical, detection and quantification limits. This method is fast, sensitive and precise and easy to transfer to wine quality control. Finally, the proposed method was applied to the determination of the aforementioned sulphur compounds in 32 red and white wines. PMID- 17279597 TI - Use of an integrated MS--multiplexed MS/MS data acquisition strategy for high coverage peptide mapping studies. AB - Liquid chromatography/mass spectrometry (LC/MS) peptide maps have become a basic tool for characterizing proteins of biological and pharmaceutical interest. The ability to generate reproducible maps with high protein sequence coverage is a central goal of methods development. We have applied a recently developed analytical approach (termed LC/MS(E)) to LC/MS peptide mapping. Using the LC/MS(E) approach, the mass detector alternates between a low-energy scanning mode (MS) for accurate mass peptide precursor identification, and an elevated energy mode (MS(E)) for generation of accurate mass multiplex peptide fragmentation data. In this paper, we evaluate this analytical approach against a tryptic digest of yeast enolase. From the low-energy data, high peptide map coverage (98% of sequence from peptides >3 amino acids) was reproducibly obtained. The MS signal for essentially equimolar peptides varied over 2 orders of magnitude in intensity, and peptide intensities could be precisely and reproducibly measured. Using the temporal constraint that MS(E) peptide fragment ions exhibit chromatographic profiles that parallel the precursor ions that generated them, we were able to produce accurate mass time-resolved MS/MS information for all enolase peptides with sufficient abundance to produce a detectable fragment ion. PMID- 17279600 TI - Evaluation of sample fractionation using micro-scale liquid-phase isoelectric focusing on mass spectrometric identification and quantitation of proteins in a SILAC experiment. AB - Mass spectrometric methods based on stable isotopes have shown great promise for identification and quantitation of complex mixtures. Stable isotope labelling by amino acids in cell culture (SILAC) is a straightforward and accurate procedure for quantitation of proteins from cell lines, that are cultured in media containing the natural amino acid or its isotopically labelled analogue, giving rise to either 'light' or 'heavy' proteins. The two cell populations are pooled and treated as a single sample, which allows the use of various protein purification methods without introducing errors into the quantitative analysis. The quantitation of the proteins is based on the intensities of the light and heavy peptides. The increased number of peptides in a quantitative experiment arising from peptide pairs implies that prefractionation is critical prior to liquid chromatography/mass spectrometric (LC/MS) analysis to minimise signal suppression effects and errors in measurements of the intensity ratios. In this study, the effect of a prefractionation step on identification and quantitation of proteins in a SILAC experiment was evaluated. We show that micro-scale liquid phase isoelectric focusing in the Micro Rotofor separates proteins into well defined fractions and reduces the sample complexity. Furthermore, the fractionation enhanced the number of identified proteins and improved their quantitation. PMID- 17279599 TI - Quantitative analysis of 23-hydroxybetulinic acid, a novel anticancer substance, in the cellular environment of a human colon adenocarcinoma cell line for cellular pharmacokinetic studies. AB - In order to study the cellular distribution and kinetics of a new anticancer substance, 23-hydroxybetulinic acid, a simple, reproductive and sensitive high performance liquid chromatography/mass spectrometric (HPLC/MS) method was developed to quantify its trace concentration in cell suspension and cell culture medium. This method involved a liquid-liquid extraction with diethyl ether and a subsequent analysis performed on a Shimadzu LCMS 2010A system which contained an electrospray ionization interface. Separation was achieved by HPLC on a Zorbax Extend-C18 column with gradient elution using a mix of acetonitrile and water containing triethylamine and acetate-triethylamine as the mobile phase. A total analytical run was achieved within 6.5 min and the calibration curve was linear over a wide concentration range of 1.0-1000.0 nM for both cell suspension and culture medium. Intra- and inter-batch accuracy and precision were acceptable for both matrices. The described assay method was successfully applied to cellular pharmacokinetic studies in a human colon adenocarcinoma cell line (Caco-2) and its application of measuring the cellular concentrations of 23-hydroxybetunilic acid could be extended to different cultured cell lines. PMID- 17279601 TI - New liquid chromatography/electrospray ionisation tandem mass spectrometry measurement procedure for quantitative analysis of human insulin in serum. PMID- 17279604 TI - Adduct simplification in the analysis of cyanobacterial toxins by matrix-assisted laser desorption/ionization mass spectrometry. AB - A novel method for simplifying adduct patterns to improve the detection and identification of peptide toxins using matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry is presented. Addition of 200 microM zinc sulfate heptahydrate (ZnSO(4) . 7H(2)O) to samples prior to spotting on the target enhances detection of the protonated molecule while suppressing competing adducts. This produces a highly simplified spectrum with the potential to enhance quantitative analysis, particularly for complex samples. The resulting improvement in total signal strength and reduction in the coefficient of variation (from 31.1% to 5.2% for microcystin-LR) further enhance the potential for sensitive and accurate quantitation. Other potential additives tested, including 18-crown-6 ether, alkali metal salts (lithium chloride, sodium chloride, potassium chloride), and other transition metal salts (silver chloride, silver nitrate, copper(II) nitrate, copper(II) sulfate, zinc acetate), were unable to achieve comparable results. Application of this technique to the analysis of several microcystins, potent peptide hepatotoxins from cyanobacteria, is illustrated. PMID- 17279603 TI - Analysis of bone minerals by time-of-flight secondary ion mass spectrometry: a comparative study using monoatomic and cluster ions sources. AB - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is an important tool for the analysis of bone minerals at implant surfaces. Most studies have been performed with monoatomic primary ion sources such as Ga(+) with poor secondary molecular ion production efficiency and only elemental distributions and minor fragments of bone minerals have been reported. By using cluster ion sources, such as Au(1-3) (+) and Bi(1-3) (+), identification of larger hydroxyapatite species at m/z 485, 541, 597 and 653, identified as Ca(5)P(3)O(12), Ca(6)P(3)O(13), Ca(7)P(3)O(14) and Ca(8)P(3)O(15), respectively, became possible. The ions appear to be fragments of the hydroxyapatite unit cell Ca(10)(PO(4))(6)(OH)(2). Each ion in the series is separated by 55.9 m/z units, corresponding to CaO, and this separation might reflect the columnar nature of the unit cell. PMID- 17279605 TI - Structural analysis of O-glycopeptides employing negative- and positive-ion multi stage mass spectra obtained by collision-induced and electron-capture dissociations in linear ion trap time-of-flight mass spectrometry. AB - Structural analyses of various glycans attached to proteins and peptides are highly desirable for elucidating their biological roles. An approach based on mass spectrometry (MS) combining both collision-induced dissociation (CID) and electron-capture dissociation (ECD) in the positive- and negative-ion modes has been proposed as a simple and direct method of assigning an O-glycan without releasing it from the peptide and of determining the amino acid sequence of the peptide and glycosylation site. The instrument used is an electrospray ionization (ESI) linear ion trap (LIT) time-of-flight (TOF) mass spectrometer with tandem LITs for CID by He gas and ECD. The proposed approach was tested with two synthetic O-glycopeptides binding a sialyl Lewis x (sLe(x)) oligosaccharide and a 3'-sialyl N-acetyllactosamine (3'-SLN) on a serine (S) residue. In the negative ion mode, the CID MS(2) spectra of O-glycopeptides showed a relatively abundant glycoside-bond cleavage between the core N-acetylglucosamine (GlcNAc) and serine (S) that yields deprotonated C(3)-type fragment ions of O-glycan and deprotonated Z(0)-type peptide ions. The structure of the sLe(x) (3'-SLN) oligosaccharide was simply assigned by comparing the CID MS(3) spectrum derived from the C(3)-type fragment ion with the CID MS(2) spectra of the sLe(x) and sLe(a) (3'- and 6'-SLN) standards (i.e., negative-ion MS(n) spectral matching). The amino acid sequence of the peptide including the glycosylation site was determined from the ECD MS(2) spectrum in the positive-ion mode. PMID- 17279606 TI - Investigation of heptakis(2,6-di-O-methyl)-beta-cyclodextrin inclusion complexes with flavonoid glycosides by electrospray ionization mass spectrometry. AB - The non-covalent complexes between three flavonoid glycosides (quercitrin, hyperoside and rutin) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta CD) were investigated by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS). The 1:1 complexation of each flavonoid glycoside (guest) to the DM-beta-CD (host) was monitored in the negative ion mode by mixing each guest with an up to 30-fold molar excess of the host. The binding constants for all complexes were calculated by a linear equation in the order: DM-beta-CD:quercitrin > DM-beta-CD:rutin > DM-beta CD:hyperoside. A binding model for the complexes has also been proposed based on the binding constants and tandem mass spectrometric data of these complexes. PMID- 17279607 TI - A potential pitfall in 18O-based N-linked glycosylation site mapping. AB - A common procedure for identifying N-linked glycosylation sites involves tryptic digestion of the glycoprotein, followed by the conversion of glycosylated asparagine residues into (18)O-labeled aspartic acids by PNGase F digestion in (18)O water. The 3 Da mass tag created by this process is readily observable by liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis, and is often used to identify the sites of N-linked glycosylation. While using this procedure, we noticed that 60% of the asparagines identified as being glycosylated were not part of the consensus sequence required for N-linked glycosylation, and thus were not biologically possible. Investigation into the source of this unacceptably high false positive rate demonstrated that even after reversed-phase cleanup and heat denaturation, the trypsin used for proteolysis was still active and led to the incorporation of (18)O into the C-termini of the peptides during the deglycosylation step. The resulting mass shift accounted for most of the false positive sites, as the database search algorithm confused it with an (18)O labeled Asp residue near the C-terminus of a peptide. This problem can be overcome by eliminating trypsin from the solution prior to performing the deglycosylation process, by resuspending the peptides in natural abundance water following deglycosylation, or by allowing (18)O incorporation into the C-terminus as a variable modification during the database search. These methods have been demonstrated on a model protein, and are applicable to the analyses of glycoproteins that are digested with trypsin or another serine protease prior to enzymatic release of the carbohydrate side chains. This study should alert investigators in the field to this potential and unexpected pitfall and provide strategies to overcome this phenomenon. PMID- 17279608 TI - Supercritical fluid extraction and quantification of aflatoxins in Zizyphi Fructus by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry. AB - An integrated method combining supercritical fluid extraction (SFE) with liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (LC/APCI-MS/MS) was developed and successfully applied to quantify aflatoxins (AFs) in Zizyphi Fructus (fruits of Zizyphus jujube), a traditional Chinese medicine. To minimize the potential interferences caused by the complex matrix in Zizyphi Fructus, a SFE pretreatment was performed. In addition, electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) spectra were also compared. The results showed that the calibration curves of AFB(1), AFB(2), AFG(1), and AFG(2) were all linear over the range of concentration from 1 to 50 ng/g, the squared correlation coefficients (r(2)) were over 0.995, and the detection limits of the method were between 0.17 and 0.32 ng/g. It showed high recovery and good precision in quantitating AFs in Zizyphi Fructus without further clean-up. Further, fragmentation pathways of protonated AFs in APCI-MS/MS were clearly proposed which could predict the existence of AFB or AFG series. To test the empirical validity of the proposed methodology in this paper, eight random samples of Zizyphi Fructus collected from supermarkets and traditional Chinese medicine stores in different geographical areas of Taiwan were analyzed. The results indicated that low levels of AFs were detected in only one of them. PMID- 17279609 TI - Quality of life of patients with gastric cancer in Taiwan: validation and clinical application of the Taiwan Chinese version of the EORTC QLQ-C30 and EORTC QLQ-STO22. AB - The relatively high incidence of gastric cancer in Taiwan warranted the need of a disease-specific quality of life (QOL) instrument. We translated the EORTC QLQ C30 and QLQ-STO22 according to the guidelines from the EORTC. A total of 100 patients were interviewed. Convergent and discriminant validity, Cronbach's alpha coefficient and known-groups comparisons were used to examine the reliability and validity. We found good reliability for multi-item subscales of the QLQ-C30 and QLQ-STO22 (Cronbach's alpha coefficient: 0.70-0.94) except cognitive functioning of the QLQ-C30 and eating restriction of the QLQ-STO22. Patients in the active treatment group experienced compromised functional status and worse treatment associated symptoms than those in the follow-up group. Similar results were found in comparisons based on Eastern Cooperative Oncology Group (ECOG) Performance Status and dysphagia grades. The study has ascertained the cross-cultural validity, reliability and clinical applicability of the Taiwan Chinese version of the EORTC QLQ-C30 and QLQ-STO22. PMID- 17279611 TI - How protein transmembrane segments sense the lipid environment. AB - Integral membrane proteins have central roles in a vast number of vital cellular processes. A structural feature that most membrane proteins have in common is the presence of one or more alpha-helices with which they traverse the lipid bilayer. Because of the interaction with the surrounding lipids, the organization of these transmembrane helices will be sensitive to lipid properties like lateral packing, hydrophobic thickness, and headgroup charge. The helices may adapt to the lipids in different ways, which in turn can influence the structure and function of the intact membrane protein. In this review, we will focus on how the lipid environment influences two specific properties of transmembrane segments: their lateral association and their tilt with respect to the bilayer normal. PMID- 17279610 TI - Listeria-based vaccines can overcome tolerance by expanding low avidity CD8+ T cells capable of eradicating a solid tumor in a transgenic mouse model of cancer. AB - We have created a transgenic mouse with tissue-specific expression of the human papilloma virus (HPV) 16 E6 and E7 oncoproteins in the thyroid as a model of HPV transformed cancer. The expression of the transgenes results in the formation of palpable thyroid tumors. E7 is not expressed in other tissues but is expressed in medullary thymic epithelial cells, which have been implicated in the control of negative selection. We show that Listeria-based vaccines against E7 can induce the regression of solid implanted tumors in the transgenic mice, although at a lower frequency than in wild type (WT) mice. E7-specific CD8+ T cells induced in transgenic mice are of both lower avidity and lower frequency when compared to the WT mice. In this model, Listeria-based vaccines against E7 appear to be overcoming central tolerance by expanding low avidity CD8+ T cells specific for E7 that are not deleted during thymopoesis and can eliminate solid tumors. PMID- 17279612 TI - Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase. AB - The relationship between binding of transition state analogues (TSAs) and catalysis is an open problem. A recent study of the binding of phenolate TSAs to ketosteroid isomerase (KSI) found a small change in the binding energy with a change in charge delocalization of the TSAs. This has been taken as proof that electrostatic effects do not contribute in a major way to catalysis. Here we reanalyze the relationship between the binding of the TSAs and the chemical catalysis by KSI as well as the binding of the transition state (TS), by computer simulation approaches. Since the simulations reproduce the relevant experimental results, they can be used to quantify the different contributions to the observed effects. It is found that the binding of the TSA and the chemical catalysis represent different thermodynamic cycles with very different electrostatic contributions. While the binding of the TSA involves a small electrostatic contribution, the chemical catalysis involves a charge transfer process and a major electrostatic contribution due to the preorganization of the active site. Furthermore, it is found that the electrostatic preorganization contributions to the binding of the enolate intermediate of KSI and the TS are much larger than the corresponding effect for the binding of the TSAs. This reflects the dependence of the preorganization on the orientation of the nonpolar form of the TSAs relative to the oxyanion hole. It seems to us that this work provides an excellent example of the need for computational studies in analyzing key experimental findings about enzyme catalysis. PMID- 17279613 TI - Crystal structure of Arabidopsis PII reveals novel structural elements unique to plants. AB - The 1.9 A resolution crystal structure of PII from Arabidopsis thaliana reveals for the first time the molecular structure of a widely conserved regulator of carbon and nitrogen metabolism from a eukaryote. The structure provides a framework for understanding the arrangement of highly conserved residues shared with PII proteins from bacteria, archaea, and red algae as well as residues conserved only in plant PII. Most strikingly, a highly conserved segment at the N terminus that is found only in plant PII forms numerous interactions with the alpha2 helix and projects from the surface of the homotrimer opposite to that occupied by the T-loop. In addition, solvent-exposed residues near the T-loop are highly conserved in plants but differ in prokaryotes. Several residues at the C terminus that are also highly conserved only in plants contribute part of the ATP binding site and likely participate in an ATP-induced conformational change. Structures of PII also reveal how citrate and malonate bind near the triphosphate binding site occupied by ATP in bacterial and archaeal PII proteins. PMID- 17279614 TI - Insight into the radical mechanism of phycocyanobilin-ferredoxin oxidoreductase (PcyA) revealed by X-ray crystallography and biochemical measurements. AB - The X-ray crystal structure of the substrate-free form of phycocyanobilin (PCB) ferredoxin oxidoreductase (PcyA; EC 1.3.7.5) from the cyanobacterium Nostoc sp. PCC7120 has been solved at 2.5 A resolution. A comparative analysis of this structure with those recently reported for substrate-bound and substrate-free forms of PcyA from the cyanobacterium Synechocystis sp. PCC6803 (Hagiwara et al. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 27-32; Hagiwara et al. (2006) FEBS Lett. 580, 3823-3828) provides a compelling picture of substrate-induced changes in the PcyA enzyme and the chemical basis of PcyA's catalytic activity. On the basis of these structures and the biochemical analysis of site-directed mutants of Nostoc PcyA, including mutants reported in recent studies (Tu et al. (2006) J. Biol. Chem. 281, 3127-3136) as well as mutants described in this study, a revised mechanism for the PcyA-mediated four-electron reduction of biliverdin IXalpha to 3E/3Z-phycocyanobilin via enzyme-bound bilin radical intermediates is proposed. The mechanistic insight of these studies, along with homology modeling, have provided new insight into the catalytic mechanisms of other members of the ferredoxin-dependent bilin reductase family that are widespread in oxygenic photosynthetic organisms. PMID- 17279615 TI - The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. AB - 4-Hydroxynonenal (4-HNE), formed as a consequence of oxidative stress, exists at increased concentrations in Alzheimer's disease (AD) patients and is found in amyloid beta peptide (Abeta) plaques associated with AD. Although it remains an open question as to whether oxidative stress is a causative factor or a consequence of AD, we show here that 4-HNE, putatively resulting from the peroxidation of lipids, covalently modifies Abeta, triggering its aggregation. These Abeta modifications result from 1,4 conjugate addition and/or Schiff base formation, they occur at multiple locations on a single Abeta peptide, and they result in covalent cross-linking of Abeta peptides. The consequence of these reactions is that 4-HNE accelerates the formation of Abeta protofibrils while inhibiting the production of straight, mature fibrils. Recent studies implicating Abeta oligomers and protofibrils in the neurotoxic process that ultimately leads to AD suggest that the Abeta aggregates induced by 4-HNE may be important in the pathogenesis of AD. These results provide further incentive to understand the role of oxidative stress and small-molecule Abeta modifications in sporadic AD. PMID- 17279617 TI - Clavulanic acid dehydrogenase: structural and biochemical analysis of the final step in the biosynthesis of the beta-lactamase inhibitor clavulanic acid. AB - The ultimate step in the biosynthesis of the medicinally important beta-lactamase inhibitor clavulanic acid is catalyzed by clavulanic acid dehydrogenase (CAD). CAD is responsible for the NAPDH-dependent reduction of the unstable intermediate clavulanate-9-aldehyde to yield clavulanic acid. Here, we report biochemical and structural studies on CAD. Biophysical analyses demonstrate that CAD exists as dimeric and tetrameric species in solution. The reaction performed by CAD was shown to be reversible, allowing the use of clavulanic acid for activity analyses. The crystal structure of CAD was solved using single-wavelength anomalous diffraction with a seleno-methionine derivative. The structure reveals that the individual monomers comprise a single domain possessing the Rossmann fold, characteristic of dinucleotide-binding enzymes. The monomers are arranged as tetramers, similar to other tetrameric members of the short-chain dehydrogenase/reductase family. The structure of the unreactive complex of CAD with clavulanic acid and NADPH suggests how CAD is able to catalyze the reduction of clavulanate-9-aldehyde without fragmentation of the bicyclic beta-lactam ring structure. The relative positions of NADPH and clavulanic acid, in the active site, together with the presence of the latter in an eclipsed conformation, rationalizes previous labeling studies demonstrating that the incorporation of the C5 pro-R, but not pro-S, hydrogen of ornithine/arginine into the C9 position of clavulanic acid occurs with overall inversion of configuration. PMID- 17279616 TI - NMR structures of (rGCUGAGGCU)2 and (rGCGGAUGCU)2: probing the structural features that shape the thermodynamic stability of GA pairs. AB - The NMR structures of [see text] and [see text] are reported. The internal loop, [see text], is about 2 kcal/mol more stable than [see text] at 37 degrees C. The duplexes assemble into similar global folds characterized by the formation of tandem sheared GA pairs. The different stabilities of the loops are accompanied by differences in the local structure of the closing GU pairs. In the [see text] internal loop, the GU pairs form canonical wobble configurations with two hydrogen bonds, whereas in [see text], the GU pairs form a single hydrogen bond involving the amino group, GH22, and the carbonyl group, UO4. This pairing is similar to the GU closing pair of the 690 hairpin loop found in E. coli 16S rRNA. The [see text] and [see text] structures reveal how the subtle interplay between stacking and hydrogen bonding determines sequence dependent conformation and thermodynamic stability. Thus, this work provides structural and thermodynamic benchmarks for theoreticians in the ongoing effort to understand the sequence dependence of RNA physicochemical properties. PMID- 17279618 TI - Aspartate isomerization in the complementarity-determining regions of two closely related monoclonal antibodies. AB - The aspartic acid residues (Asp) present in the complementarity-determining regions (CDRs) of the light chains of two recombinant monoclonal antibodies (MAbs), MAb I and MAb II, are highly susceptible to isomerization due to the presence of glycine residues (Gly) on their C-terminal ends. Asp isomerization in these MAbs leads to formation of the isoaspartate (IsoAsp) and the cyclic imide (Asu) variants of these MAbs. Both MAb I and MAb II, employed in this study, elicit their pharmacological responses through binding human IgE. The formation of the MAb variants as a result of Asp isomerization significantly reduces the binding affinities of these antibodies to IgE, thereby reducing their potencies. Here we report on significant differences in the susceptibility of the MAb I and the MAb II to Asp isomerization. The molecular basis for these differences in rates of Asp isomerization was elucidated. The effect of primary sequence on Asp isomerization was evaluated using pentapeptide models of the MAbs, which included the labile Asp residues and their neighboring amino acid residues. The separation of the parent MAbs and pentapeptides from their isomerization products was achieved using hydrophobic interaction chromatography (HIC) and rp-HPLC, respectively. Structural characterization of the MAbs was performed using differential scanning calorimetry (DSC), circular dichroism (CD), and X-ray crystallography. Our investigations demonstrate that the differences in the Asp isomerization rates between MAb I and MAb II can be attributed to structural factors including the conformational flexibility and the extent of solvent exposure of the labile Asp residue. PMID- 17279619 TI - Folding mechanisms of proteins with high sequence identity but different folds. AB - The problem of how a protein folds from a linear chain of amino acids to the three-dimensional structure necessary for function is often investigated using proteins with a low degree of sequence identity that adopt different folds. The design of pairs of proteins with a high degree of sequence identity but different folds offers the opportunity for a complementary study; in two highly similar sequences, which residues are the most important in directing folding to a particular structure? Here we use molecular dynamics simulations to characterize the folding-unfolding pathways of a pair of proteins designed by Bryan and co workers [Alexander, P. A., et al. (2005) Biochemistry 44, 14045-14054; He, Y. N., et al. (2005) Biochemistry 44, 14055-14061]. Despite being 59% identical, the two protein sequences fold to two different structures. The first sequence folds to the alpha+beta protein G structure and the second to the all-alpha-helical protein A structure. We show that the final protein structure is determined early along the folding pathway. In folding to the protein G structure, the single alpha-helix (alpha1) and the beta3-beta4 turn fold early. Formation of the hairpin turn essentially prevents folding to helical structure in this region of the protein. This early structure is then consolidated by formation of long-range hydrophobic interactions between alpha1 and the beta3-beta4 turn. The protein A sequence differs both in the residues that form the beta3-beta4 turn and also in many of the residues that form the early hydrophobic interactions in the protein G structure. Instead, in the protein A sequence, a more hierarchical mechanism is observed, with helices folding before many of the tertiary interactions are formed. We find that small, but critical, sequence differences determine the topology of the protein early along the folding pathway, which help to explain the process by which one fold can evolve into another. PMID- 17279621 TI - Insulin amyloid fibrils form an inclusion complex with molecular iodine: a misfolded protein as a nanoscale scaffold. AB - The study describes formation of an intensely violet inclusion complex of insulin amyloid fibrils and molecular iodine. Resonance Raman spectra of complexes formed by staining mature insulin fibrils with iodine and by seeding fibrils in the presence of iodine imply similar topologies of entrapped iodine and oligoiodide species. Iodine captured by growing fibrils remains accessible to a bulk chemical reagent. In light of its small size and the fact that iodine can partition into polar as well as nonpolar media, the data suggest that intrafibrillar structure of insulin amyloid is densely packed with no appreciable void volumes capable of accommodating iodine atoms. The complex is stable: only drastic perturbation of the beta-pleated fibrous scaffold by dimethyl sulfoxide (rather than of the beta sheet conformation) leads to the release of iodine atoms from surface moieties. While the reaction between iodine and in vivo amyloid deposits was first described by Virchow in the 19th Century [Virchow, R. (1854) Virchows Arch. 6, 268-271], the underlying molecular mechanism has not been thoroughly explored since then. This work shows how the long-forgotten concept can be utilized as a probe of void volumes in protein fibrils, providing a new tool for structural studies on amyloids, and a model for design of protein-based drug delivery media. PMID- 17279620 TI - Probing the mechanism of the hamster mitochondrial folate transporter by mutagenesis and homology modeling. AB - The mitochondrial folate transporter (MFT) was previously identified in human and hamster cells. Sequence homology of this protein with the inner mitochondrial membrane transporters suggested a domain structure in which the N- and C-termini of the protein are located on the mitochondrial intermembrane-facing surface, with six membrane-spanning regions interspersed by two intermembrane loops and three matrix-facing loops. We now report the functional significance of insertion of the c-myc epitope into the intermembrane loops and of a series of site directed mutations at hamster MFT residues highly conserved in orthologues. Insertional mutagenesis in the first predicted intermembrane loop eliminated MFT function, but the introduction of a c-myc peptide into the second loop was without effect. Most of the hamster MFT residues studied by site-directed mutagenesis were remarkably resilient to these mutations, except for R249A and G192E, both of which eliminated folate transport activity. Homology modeling, using the crystal structure of the bovine ADP/ATP carrier (AAC) as a scaffold, suggested a similar three-dimensional structure for the MFT and the AAC. An ion pair interaction in the AAC thought to be central to the mechanism of membrane penetration by ADP is predicted by this homology model to be replaced by a pi cation interaction in MFT orthologues and probably also in other members of the family bearing the P(I/L)W motif. This model suggests that the MFT R249A and G192E mutations both modify the base of a basket-shaped structure that appears to constitute a trap door for the flux of folates into the mitochondrial matrix. PMID- 17279622 TI - Covalent and noncovalent modifications induce allosteric binding behavior in a monoclonal antibody. AB - Detailed equilibrium binding studies were conducted on a monoclonal antibody (8A11) directed against UO22+ complexed with 2,9-dicarboxy-1,10-phenanthroline (DCP-UO22+). Covalent modification of 8A11 with amine-reactive derivatives of Cy5 or Alexa 488 altered the binding curves obtained with DCP-UO22+ from hyperbolic to sigmoidal, the latter characterized by Hill coefficients of 1.5-1.6. Binding curves obtained with DCP-UO22+ and the bivalent (Fab)2 or the monovalent Fab fragments derived from limited proteolysis of the covalently modified 8A11 were characterized by Hill coefficients of 1.2 and 1.0, respectively. Incubation of 8A11 with saturating concentrations of the Fab fragments of goat antibodies directed against the Fc portion of mouse IgG increased the affinity of the native 8A11 for DCP-UO22+ by 3-fold. Conversely, incubation of the 8A11-Cy5 covalent conjugate with saturating concentrations of protein G (which likewise binds to the constant regions of mouse IgG) decreased the affinity of the primary antibody for DCP-UO22+ by 4-fold. In addition, the binding curves obtained with 8A11-Cy5 and DCP-UO22+ species changed from sigmoidal to hyperbolic at high concentrations of protein G. The presence of the antigen had a reciprocal effect on the binding of protein G to the 8A11-Cy5 conjugate; incubation of the 8A11-Cy5 conjugate with saturating concentrations of DCP-UO22+ decreased the affinity of the conjugate for protein G by 20-fold. These complex binding data were interpreted in terms of a free energy binding model in which (i) 2 mol of DCP-UO22+ and 1 mol of protein G bind to each mole of the 8A11-Cy5 conjugate, (ii) binding of the first equivalent of DCP-UO22+ to the antibody promotes the binding of the second equivalent of antigen in the absence of protein G, and (iii) DCP-UO22+ and protein G oppose each other's binding to the antibody. This is the first detailed description of the energetic balance of reciprocal binding events among the antigen binding sites and distant points on the constant portion of an immunoglobulin. PMID- 17279623 TI - Conformations of alanine-based peptides in water probed by FTIR, Raman, vibrational circular dichroism, electronic circular dichroism, and NMR spectroscopy. AB - We have used a combination of FTIR, VCD, ECD, Raman, and NMR spectroscopies to probe the solution conformations sampled by H-(AAKA)-OH by utilizing an excitonic coupling model and constraints imposed by the 3JCalphaHNH coupling constants of the central residues to simulate the amide I' profile of the IR, isotropic Raman, anisotropic Raman, and VCD spectra in terms of a mixture of three conformations, i.e., polyproline II, beta-strand and right-handed helical. The representative coordinates of the three conformations were obtained from published coil libraries. Alanine was found to exhibit PPII fractions of 0.60 or greater, mixed with smaller fractions of helices and beta-strand conformations. Lysine showed no clear conformational propensity in that it samples polyproline II, beta-strand, and helical conformations with comparable probability. This is at variance with results obtained earlier for ionized polylysine, which suggest a high polyproline II propensity. We reanalyzed previously investigated tetra- and trialanine by combining published vibrational spectroscopy data with 3JCalphaHNH coupling constants and obtained again blends dominated by PPII with smaller admixtures of beta-strand and right-handed helical conformations. The polyproline II propensity of alanine was found to be higher in tetraalanine than in trialanine. For all peptides investigated, our results rule out a substantial population of turn-like conformations. Our results are in excellent agreement with MD simulations on short alanine peptides by Gnanakaran and Garcia [(2003) J. Phys. Chem. B 107, 12555-12557] but at variance with multiple MD simulations particularly for the alanine dipeptide. PMID- 17279624 TI - Characterization of the RFX complex and the RFX5(L66A) mutant: implications for the regulation of MHC class II gene expression. AB - Major histocompatability complex class II (MHCII) molecules are an essential component of the mammalian adaptive immune response. The expression of MHCII genes is regulated by a cell-specific multiprotein complex, termed the MHCII enhanceosome. The heterotrimeric RFX complex is the key DNA-binding component of the MHCII enhanceosome. The RFX complex is comprised of three proteins, RFXB, RFXAP, and RFX5, all of which are required for DNA binding and activation of MHCII gene expression. Static light scattering and chemical cross-linking of the three RFX proteins show that RFXB and RFXAP are monomers and that RFX5 dimerizes through two separate domains. One of these domains, the oligomerization domain, promotes formation of a dimer of dimers of RFX5. In addition, we show that the RFX complex forms a 2:1:1 complex of RFX5.RFXAP.RFXB, which can associate with a further dimer of RFX5 to form a 4:1:1 complex through the oligomerization domain of RFX5. On the basis of these studies, we propose DNA-binding models for the interaction between the RFX complex and the MHCII promoter including a DNA looping model. We also provide direct evidence that the RFX5(L66A) point mutation prevents dimerization of the RFX complexes and propose a model for how this results in a loss of MHCII gene expression. PMID- 17279625 TI - Biochemical characterization of RAR1 cysteine- and histidine-rich domains (CHORDs): a novel class of zinc-dependent protein-protein interaction modules. AB - Disease resistance in plants requires the activation of defense signaling pathways to prevent the spread of infection. The protein Required for Mla12 Resistance (RAR1) is a component of such pathways, which contains cysteine- and histidine-rich domains (CHORDs) that bind zinc. CHORDs are 60 amino acid domains, usually arranged in tandem, found in almost all eukaryotes, where they are involved in processes ranging from pressure sensing in the heart to maintenance of diploidy in fungi, and exhibit distinct protein-protein interaction specificity. In the case of RAR1, CHORD-I is known to interact with heat-shock protein 90 (HSP90) and CHORD-II is known to interact with the Suppressor of the G2 allele of Skp1 (SGT1). The focus of this work on RAR1 from barley and Arabidopsis was to address the paucity of biochemical information on RAR1 and its constituent CHORDs, particularly the role of the metal ion. Sedimentation experiments indicated RAR1 to be an extended monomer in solution with few intramolecular interactions. This was reinforced by denaturation experiments, where little difference between the stability of the individual domains and intact RAR1 could be detected by intrinsic tryptophan fluorescence. Electrospray ionization-mass spectrometry and atomic absorption showed that, contrary to previous reports, RAR1 binds five zinc ions; each CHORD binds two, and the plant specific, 20 amino acid cysteine- and histidine-containing motif (CCCH motif) located between the two CHORDs binds the fifth. Fluorescence, ultraviolet circular dichroism (UV CD), and nuclear magnetic resonance (NMR) spectroscopy further demonstrated that zinc ions are essential for maintaining CHORD structure. Finally, we used isothermal titratrion colarimetry to show that zinc is essential for the specific binding interactions of CHORD-II with SGT1. Our study provides the first biochemical and biophysical data on the zinc metalloprotein RAR1, defines its metal stoichiometry and that of its constituent CHORDs, and reveals that the metal ions are essential for structural integrity and specific protein-protein associations. PMID- 17279626 TI - Conformation and lipid binding of a C-terminal (198-243) peptide of human apolipoprotein A-I. AB - Human apolipoprotein A-I (apoA-I) is the principle apolipoprotein of high-density lipoproteins that are critically involved in reverse cholesterol transport. The intrinsically flexibility of apoA-I has hindered studies of the structural and functional details of the protein. Our strategy is to study peptide models representing different regions of apoA-I. Our previous report on [1-44]apoA-I demonstrated that this N-terminal region is unstructured and folds into approximately 60% alpha-helix with a moderate lipid binding affinity. We now present details of the conformation and lipid interaction of a C-terminal 46 residue peptide, [198-243]apoA-I, encompassing putative helix repeats 10 and 9 and the second half of repeat 8 from the C-terminus of apoA-I. Far-ultraviolet circular dichroism spectra show that [198-243]apoA-I is also unfolded in aqueous solution. However, self-association induces approximately 50% alpha-helix in the peptide. The self-associated peptide exists mainly as a tetramer, as determined by native electrophoresis, cross-linking with glutaraldehyde, and unfolding data from circular dichroism (CD) and differential scanning calorimetry (DSC). In the presence of a number of lipid-mimicking detergents, above their CMC, approximately 60% alpha-helix was induced in the peptide. In contrast, SDS, an anionic lipid-mimicking detergent, induced helical folding in the peptide at a concentration of approximately 0.003% (approximately 100 microM), approximately 70-fold below its typical CMC (0.17-0.23% or 6-8 mM). Both monomeric and tetrameric peptide can solubilize dimyristoylphosphatidylcholine (DMPC) liposomes and fold into approximately 60% alpha-helix. Fractionation by density gradient ultracentrifugation and visualization by negative staining electromicroscopy demonstrated that the peptide binds to DMPC with a high affinity to form at least two sizes of relatively homogeneous discoidal HDL-like particles depending on the initial lipid:peptide ratio. The characteristics (lipid:peptide weight ratio, diameter, and density) of both complexes are similar to those of plasma A-I/DMPC complexes formed under similar conditions: small discoidal complexes (approximately 3:1 weight ratio, approximately 110 A, and approximately 1.10 g/cm3) formed at an initial 1:1 weight ratio and larger discoidal complexes (approximately 4.6:1 weight ratio, approximately 165 A, and approximately 1.085 g/cm3) formed at initial 4:1 weight ratio. The cross-linking data for the peptide on the complexes of two sizes is consistent with the calculated peptide numbers per particle. Compared to the approximately 100 A disk-like complex formed by the N-terminal peptide in which helical structure was insufficient to cover the disk edge by a single belt, the compositions of these two types of complexes formed by the C-terminal peptide are more consistent with a "double belt" model, similar to that proposed for full-length apoA-I. Thus, our data provide direct evidence that this C-terminal region of apoA-I is responsible for the self-association of apoA I, and this C-terminal peptide model can mimic the interaction with the phospholipid of plasma apoA-I to form two sizes of homogeneous discoidal complexes and thus may be responsible for apoA-I function in the formation and maintenance of HDL subspecies in plasma. PMID- 17279627 TI - Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons. AB - The cAMP-dependent protein kinase (PKA) regulates a wide array of cellular functions. In brain and heart PKA increases the activity of the L-type Ca2+ channel Cav1.2 in response to beta-adrenergic stimulation. Cav1.2 forms a complex with the beta2-adrenergic receptor, the trimeric GS protein, adenylyl cyclase, and PKA wherein highly localized signaling occurs [Davare, M. A., Avdonin, V., Hall, D. D., Peden, E. M., Burette, A., Weinberg, R. J., Horne, M. C., Hoshi, T., and Hell, J. W. (2001) Science 293, 98-101]. PKA primarily phosphorylates Cav1.2 on serine 1928 of the central, pore-forming alpha11.2 subunit. Here we demonstrate that the A-kinase anchor protein 150 (AKAP150) is critical for PKA mediated regulation of Cav1.2 in the brain. AKAP150 and MAP2B specifically co immunoprecipitate with Cav1.2 from rat brain. Recombinant AKAP75, the bovine homologue to rat AKAP150, binds directly to three different sites of alpha11.2. MAP2B from rat brain also interacts with these same sites in pull-down assays. Gene disruption of AKAP150 in mice dramatically reduces co-immunoprecipitation of PKA with Cav1.2 and prevents phosphorylation of serine 1928 upon beta-adrenergic stimulation in vivo. These results demonstrate the physiological relevance of PKA anchoring by AKAPs in general and AKAP150 specifically in the regulation of Cav1.2 in vivo. PMID- 17279628 TI - Recombinant production and properties of binding of the full set of mouse secreted phospholipases A2 to the mouse M-type receptor. AB - To date, 12 secreted phospholipases A2 (sPLA2s) have been identified in the mouse species and divided into three structural collections (I/II/V/X, III, and XII). On the basis of their different molecular properties and tissue distributions, each sPLA2 is likely to exert distinct functions by acting as an enzyme or ligand for specific soluble proteins or receptors, among which the M-type receptor is the best-characterized target. Here, we present the properties of binding of the full set of mouse sPLA2s to the mouse M-type receptor. All enzymes have been produced in Escherichia coli or insect cells, and their properties of binding to the cloned and native M-type receptor have been determined. sPLA2s IB, IIA, IIE, IIF, and X are high-affinity ligands (K0.5 = 0.3-3 nM); sPLA2s IIC and V are low affinity ligands (K0.5 = 30-75 nM), and sPLA2s IID, III, XIIA, and XIIB bind only very weakly or do not bind to the M-type receptor (K0.5 > 100 nM). Three exogenous parvoviral group XIII PLA2s and two fungal group XIV sPLA2s do not bind to the receptor. Together, these results indicate that the mouse M-type receptor is selective for only a subset of mouse sPLA2s from the group I/II/V/X structural collection. Binding of mouse sPLA2s to a recombinant soluble mouse M-type receptor leads in all cases to inhibition of enzymatic activity, and the extent of deglycosylation of the receptor decreases yet does not abolish sPLA2 binding. The physiological meaning of binding of sPLA2 to the M-type receptor is discussed on the basis of our current knowledge of sPLA2 functions. PMID- 17279630 TI - Fluorescence spectroscopic studies of pressure effects on Na+,K(+)-ATPase reconstituted into phospholipid bilayers and model raft mixtures. AB - To contribute to the understanding of membrane protein function upon application of pressure as relevant for understanding, for example, the physiology of deep sea organisms or for baroenzymological biotechnical processes, we investigated the influence of hydrostatic pressure on the activity of Na+,K+-ATPase enriched in the plasma membrane from rabbit kidney outer medulla using a kinetic assay that couples ATP hydrolysis to NADH oxidation. The data show that the activity of Na+,K+-ATPase is reversibly inhibited by pressures below 2 kbar. At higher pressures, the enzyme is irreversibly inactivated. To be able to explore the effect of the lipid matrix on enzyme activity, the enzyme was also reconstituted into various lipid bilayer systems of different chain length, conformation, phase state, and heterogeneity including model raft mixtures. To yield additional information on the conformation and phase state of the lipid bilayer systems, generalized polarization values by the Laurdan fluorescence technique were determined as well. Incorporation of the enzyme leads to a significant increase of the lipid chain order. Generally, similar to the enzyme activity in the natural plasma membrane, high hydrostatic pressures lead to a decline of the activity of the enzyme reconstituted into the various lipid bilayer systems, and in most cases, a multi-phasic behavior is observed. Interestingly, in the low pressure region, around 100 bar, a significant increase of activity is observed for the enzyme reconstituted into DMPC and DOPC bilayers. Above 100-200 bar, this activity enhancement is followed by a steep decrease of activity up to about 800 bar, where a more or less broad plateau value is reached. The enzyme activity decreases to zero around 2 kbar for all reconstituted systems measured. A different scenario is observed for the effect of pressure on the enzyme activity in the model raft mixture. The coexistence of liquid-ordered and liquid disordered domains with the possibility of lipid sorting in this lipid mixture leads to a reduced pressure sensitivity in the medium-pressure range. The decrease of ATPase activity may be induced by an increasing hydrophobic mismatch, leading to a decrease of the conformational dynamics of the protein and eventually subunit rearrangement. High pressures, above about 2.2 kbar, irreversibly change protein conformation, probably because of the dissociation and partial unfolding of the subunits. PMID- 17279632 TI - Highly luminescent Eu3+ chelate nanoparticles prepared by a reprecipitation encapsulation method. AB - Aqueous suspensions of highly luminescent Eu3+ chelate nanoparticles are prepared by a novel reprecipitation-encapsulation method. An alkyl alkoxysilane encapsulation agent is included during the nanoparticle formation process, forming a nanoparticle encapsulation layer that inhibits aggregation as evidenced by UV-vis spectroscopy and atomic force microscopy. In addition, the encapsulated nanoparticles exhibit a small size (10 nm), intense luminescence, and excellent photostability. We estimate that the molar extinction coefficients of the approximately 10 nm particles are approximately 5.0x10(7) M-1 cm-1 with a luminescence quantum yield of 6%, indicating a luminescence brightness many times larger than that of conventional fluorescent dyes and comparable to that of colloidal semiconductor quantum dots. The small size, high brightness, highly red shifted luminescence, and long luminescence lifetimes of the nanoparticles are of interest for luminescence labeling and sensing applications. PMID- 17279629 TI - The GCN4 bZIP targets noncognate gene regulatory sequences: quantitative investigation of binding at full and half sites. AB - We previously reported that a basic region/leucine zipper (bZIP) protein, a hybrid of the GCN4 basic region and C/EBP leucine zipper, not only recognizes cognate target sites AP-1 (5'-TGACTCA-3') and cAMP-response element (CRE) (5' TGACGTCA-3') but also binds selectively to noncognate DNA sites: C/EBP (CCAAT/enhancer binding protein, 5'-TTGCGCAA), XRE1 (xenobiotic response element, 5'-TTGCGTGA), HRE (HIF response element, 5'-GCACGTAG), and E-box (5'-CACGTG). In this work, we used electrophoretic mobility shift assay (EMSA) and circular dichroism (CD) for more extensive characterization of the binding of wt bZIP dimer to noncognate sites as well as full- and half-site derivatives, and we examined changes in flanking sequences. Quantitative EMSA titrations were used to measure dissociation constants of this hybrid, wt bZIP, to DNA duplexes: Full site binding affinities gradually decrease from cognate sites AP-1 and CRE with Kd values of 13 and 12 nM, respectively, to noncognate sites with Kd values of 120 nM to low microM. DNA-binding selectivity at half sites is maintained; however, half-site binding affinities sharply decrease from the cognate half site (Kd = 84 nM) to noncognate half sites (all Kd values > 2 microM). CD shows that comparable levels of alpha-helical structure are induced in wt bZIP upon binding to cognate AP-1 or noncognate sites. Thus, noncognate sites may contribute to preorganization of stable protein structure before binding target DNA sites. This work demonstrates that the bZIP scaffold may be a powerful tool in the design of small, alpha-helical proteins with desired DNA recognition properties. PMID- 17279631 TI - Specific mutations in transmembrane helix 8 of human concentrative Na+/nucleoside cotransporter hCNT1 affect permeant selectivity and cation coupling. AB - The Na+/nucleoside cotransporters hCNT1 (650 residues) and hCNT2 (658 residues) are 72% identical in amino acid sequence and contain 13 putative transmembrane helices (TMs). Both transport uridine and adenosine but are otherwise selective for pyrimidine (system cit) and purine (system cif) nucleosides, respectively. Previously, we used site-directed mutagenesis and functional expression in Xenopus oocytes to identify two pairs of adjacent residues in TMs 7 and 8 of hCNT1 (Ser319-Gln320 and Ser353-Leu354) that, when converted to the corresponding residues in hCNT2 (Gly-Met and Thr-Val, respectively), changed the permeant selectivity of the transporter from cit to cif. We now report an investigation of the effects of corresponding mutations in TM 8 alone and demonstrate unique S353T and L354V-induced changes in nucleoside specificity and cation coupling, respectively. hCNT1 mutation S353T produced a profound decrease in cytidine transport efficiency (Vmax/Km ratio) and, in combination with L354V (S353T/L354V), resulted in a novel uridine-preferring transport phenotype. In addition, the L354V mutation markedly increased the apparent affinity of hCNT1 for Na+ and Li+. Both hCNT1 TM 8 residues exhibited uridine-protectable inhibition by p-chloromercuribenzene sulfonate when converted to Cys, suggesting that they occupy positions within or closely adjacent to a common cation/nucleoside translocation pore. PMID- 17279634 TI - Electrochemically triggered Michael addition on the self-assembly of 4 thiouracil: generation of surface-confined redox mediator and electrocatalysis. AB - Generation of a surface-confined redox mediator (RM) by an electrochemically triggered Michael addition reaction and the electrocatalytic properties of the mediator are described. Electrogenerated o-quinone undergoes Michael addition reaction with the self-assembled monolayer (SAM) of 4-thiouracil (4-TU) on a gold (Au) electrode and yields a surface-confined RM, 1-(3,4-dihydroxyphenyl)-4 mercapto-1H-pyrimidin-2-one (DPTU). The Michael addition reaction depends on the electrolysis potential and time, solution pH, and concentration of catechol (CA) used in the reaction. The redox mediator, DPTU, exhibits reversible redox response, characterstic of a surface-confined species at approximately 0.22 V in neutral pH. The anodic peak potential of DPTU shifts by 58+/-2 mV while changing the solution pH by one unit, suggesting that protons and electrons taking part in the redox reaction are in the ratio of 1:1. The apparent rate constant (ksapp) for the heterogeneous electron-transfer reaction of the RM was determined to be 114+/-5 s-1. The surface coverage (Gamma) of DPTU on the electrode surface was 8.2+/-0.1x10(-12) mol/cm2. DPTU shows excellent electrocatalytic activity toward oxidation of reduced nicotinamide adenine dinucleotide (NADH) with activation overpotential, which is approximately 600 mV lower than that observed at the unmodified Au electrode. The dipositive cations in the supporting electrolyte solution amplify the electrocatalytic activity of DPTU. A 2.5-fold enhancement in the catalytic current was observed in the presence of Ca2+ or Ba2+ ions. The sensitivity of the electrode toward NADH in the presence and absence of Ca2+ ions was 0.094+/-0.011 and 0.04+/-0.0071 nA cm-2 nM-1, respectively. A linear increase in the catalytic current was obtained up to the concentration of 0.8 mM, and the electrode can detect amperometrically as low as 25 nM of NADH in neutral pH. PMID- 17279635 TI - Preparation of superhydrophobic silicon oxide nanowire surfaces. AB - The paper reports on the preparation of superhydrophobic amorphous silicon oxide nanowires (a-SiONWs) on silicon substrates with a contact angle greater than 150 degrees by means of surface roughness and self-assembly. Nanowires with an average mean diameter in the range 20-150 nm and 15-20 microm in length were obtained by the so-called solid-liquid-solid (SLS) technique. The porous nature and the high roughness of the resulting surfaces were confirmed by AFM imaging. The superhydrophobicity resulted from the combined effects of surface roughness and chemical modification with fluorodecyl trichlorosilane. PMID- 17279633 TI - Controlling the cellular uptake of gold nanorods. AB - Gold nanorods coated with cetyltrimethylammonium bromide (CTAB), a cationic micellar surfactant used in nanorod synthesis, were rapidly and irreversibly internalized by KB cells via a nonspecific uptake mechanism. Internalized nanorods near the cell surface were monitored by two-photon luminescence (TPL) microscopy and observed to migrate toward the nucleus with a quadratic rate of diffusion. The internalized nanorods were not excreted but formed permanent aggregates within the cells, which remained healthy and grew to confluence over a 5-day period. Nonspecific nanorod uptake could be greatly reduced by displacing the CTAB surfactant layer with chemisorptive surfactants, particularly by the conjugation of poly(ethylene glycol) chains onto nanorods using in situ dithiocarbamate formation. PMID- 17279636 TI - Realizing a two-dimensional ordered array of ferritin molecules directly on a solid surface utilizing carbonaceous material affinity peptides. AB - A two-dimensional hexagonally close-packed (2D-HCP) array of ferritin molecules with a nanoparticle core was fabricated directly on a carbonaceous solid substrate by genetically modifying the outer surface of the ferritin with carbonaceous materials-specific binding peptides. The displayed peptides endowed ferritins with a specific protein-substrate interaction and masked the strong nonspecific interaction. The specific interaction was weak enough to allow ferritins to be rearranged as well as an attractive protein-protein interaction that could be adjusted by selecting the buffer conditions. This method not only produced 2D-HCP arrays of ferritin but also 2D-ordered arrays of independent inorganic nanoparticles after protein elimination that can be applied to floating gate memories. PMID- 17279637 TI - The wetting of gold and silicon nanoscale arrays. AB - The relative hydrophobicity of surfaces containing highly regular, nanoscale (<100 nm) topological features (50 nm diameter, 5 nm height, 100 nm spacing) was measured and compared with their flat counterparts. The results are described in the context of both the Wenzel and Cassie models for wetting rough surfaces. Wenzel-type wetting is observed for these high areal density nanostructures (approximately 10(10)/cm2) whose aspect ratios range from 0.2 to 0.7. PMID- 17279638 TI - Physical organic chemistry of supramolecular polymers. AB - Unlike the case of traditional covalent polymers, the entanglements that determine properties of supramolecular polymers are defined by very specific, intermolecular interactions. Recent work using modular molecular platforms to probe the mechanisms underlying mechanical response of supramolecular polymers is reviewed. The contributions of supramolecular kinetics, thermodynamics, and conformational flexibility to supramolecular polymer properties in solutions of discrete polymers, in networks, and at interfaces, are described. Molecule-to material relationships are established through methods reminiscent of classic physical organic chemistry. PMID- 17279639 TI - Supramolecular complex induced by the binding of sodium dodecyl sulfate to PAMAM dendrimers. AB - Isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) were employed to study the spontaneous supramolecular complexation of amine terminated PAMAM dendrimer (G3[EDA] PAMAM-NH2) induced by the binding of an anionic surfactant, sodium dodecyl sulfate (SDS). At pHor=10, the electrostatic binding ceased because the deprotonated PAMAM dendrimer was uncharged, and hence the surfactant-induced supramolecular assembly could not be formed. PMID- 17279640 TI - Determination of drug and fatty acid binding capacity to pluronic f127 in microemulsions. AB - We propose that one can deduce very insightful information regarding the drug and fatty acid binding capacity of microemulsions through simple turbidity experiments. Pluronic F127-based oil-in-water microemulsions of various compositions were synthesized and titrated to turbidity with concentrated amitriptyline, an antidepressant drug. We observed that, above certain Pluronic F127 concentrations, turbidity was never observed, irrespective of how much amitriptyline was added to the microemulsion. We also observed that whenever sodium caprylate fatty acid was not included in the microemulsion formulation, turbidity never occurred. On the basis of these findings, we were able to determine the point at which all sodium caprylate present in the microemulsion formulation was bound to the F127 in the microemulsion (i.e., no fatty acid was free in the bulk in monomer form). By the same logic we were also able to determine how much amitriptyline was binding to the microemulsions. We also measured the dynamic surface tension, foamability, and fabric wetting time of the microemulsion formulations to further prove the hypothesis that all fatty acid is bound to the F127 in the microemulsion above a critical Pluronic F127 concentration. On the basis of this research, we have concluded that there are approximately 11 molecules of sodium caprylate fatty acid bound per molecule of Pluronic F127 and approximately 12 molecules of amitriptyline bound per molecule of Pluronic F127 in the optimal microemulsion formulation. These findings give us valuable information about the charge density at the oil/water interface and about the mechanism of binding of the drug to the microemulsion. PMID- 17279641 TI - Restructuring of colloidal cakes during dewatering. AB - Aqueous suspensions of aggregated silica particles have been dewatered to the point where the colloidal aggregates connect to each other and build a macroscopic network. These wet cakes have been compressed through the application of osmotic pressure. Some cakes offer a strong resistance to osmotic pressure and remain at a low volume fraction of solids; other cakes yield at low applied pressures, achieving nearly complete solid/liquid separation. We used small angle neutron scattering and transmission electron microscopy to determine the processes by which the particles move and reorganize during cake collapse. We found that these restructuring processes follow a general course composed of three stages: (1) at all scales, voids are compressed, with large voids compressed more extensively than smaller ones; the local order remains unchanged; (2) all voids with diameters in the range of 2-20 particle diameters collapse, and a few dense regions (lumps) are formed; and (3) the dense lumps build a rigid skeleton that resists further compression. Depending on the nature of interparticle bonds, some cakes jump spontaneously into stage 3 while others remain stuck in stage 1. To elucidate the relation between bond strength and compression resistance, we have constructed a numerical model of the colloidal network. In this model, particles interact through noncentral forces that are produced by springs attached to their surfaces. Networks made of bonds that break upon stretching evolve through a plastic deformation that reproduces the three stages of restructuring evidenced by the experiments. Networks made of bonds that are fragile jump into stage 3. Networks made of bonds that can be stretched without breaking evolve through elastic compression and restructure only according to stage 1. PMID- 17279643 TI - Effect of solid volume fraction on aggregation and breakage in colloidal suspensions in batch and continuous stirred tanks. AB - Aggregation and breakage of aggregates of fully destabilized polystyrene latex particles in turbulent flow was studied experimentally in both batch and continuous stirred tanks. Small-angle static light scattering (SASLS) was used to monitor the time evolution of two independent moments of the cluster mass distribution (CMD), namely, the mean radius of gyration and the zero angle scattered light intensity. In addition, information about the structure of the aggregates was obtained in terms of the static light scattering structure factor. It was observed that decreasing the solid volume fraction over more than one order of magnitude resulted in monotonically decreasing steady-state values of both moments of the CMD. Using a combination of batch operation and continuous dilution with particle-free solution in the stirred tank, it was found that the steady-state distributions were fully reversible upon changing the solid volume fraction. These observations indicate that the steady-state CMD in this system is controlled by the dynamic equilibrium between aggregation (with the second-order kinetics in cluster concentration) and breakage (with the first-order kinetics in cluster concentration). In addition, by dilution to very low solid volume fractions, we demonstrate the existence of a critical aggregate size below which breakage is negligible. PMID- 17279642 TI - Aqueous-phase behavior of natural glycolipid biosurfactant mannosylerythritol lipid A: sponge, cubic, and lamellar phases. AB - The aqueous-phase behavior of mannosylerythritol lipid A (MEL-A), which is a glycolipid biosurfactant produced from vegetable oils by yeast strains of the genus Pseudozyma, was investigated using polarized optical microscopy, small angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). MEL-A was found to self-assemble into a variety of distinctive lyotropic liquid crystals including sponge (L3), bicontinuous cubic (V2), and lamella (Lalpha) phases. On the basis of SAXS measurements, we determined the structure of the liquid crystals. The estimated lattice constant for Lalpha was 3.58 nm. DSC measurement revealed that the phase transition enthalpies from the liquid crystal to the fluid isotropic phase were in the range of 0.22-0.44 kJ/mol. Although the present MEL-A phase diagram closely resembled that obtained from relatively hydrophobic poly(oxyethylene) or fluorinated surfactants, the MEL-A L3 region was spread considerably over a wide temperature range (20-65 degrees C) compared to L3 of those surfactants: this is probably due to the unique structure which is molecularly engineered by microorganisms. In this paper, we clarify the aqueous phase diagram of the natural glycolipid biosurfactant MEL-A, and we suggest that the obtained lyotropic crystals are potentially useful as novel nanostructured biomaterials. PMID- 17279644 TI - Thermodiffusion of charged colloids: single-particle diffusion. AB - An expression for the single-particle thermal diffusion coefficient of a charged colloidal sphere is derived on the basis of force balance on the Brownian time scale in combination with thermodynamics. It is shown that the single-particle thermal diffusion coefficient is related to the temperature dependence of the reversible work necessary to build the colloidal particle, including the core, the solvation layer, and the electrical double layer. From this general expression, an explicit expression for the contribution of the electrical double layer to the single-particle thermal diffusion coefficient is derived in terms of the surface charge density of the colloidal sphere, the electrostatic screening length, and its core radius, to within the Debye-Huckel approximation. This result is shown to explain experimental data, for both thin and thick double layers. In addition, a comparison with other theories is made. PMID- 17279645 TI - A pH-study of n-dodecyl-beta-D-maltoside foam films. AB - The influence the pH has on the properties of foam films stabilized by the nonionic surfactant n-dodecyl-beta-d-maltoside (beta-C12G2) was studied. Foam film measurements were carried out with the thin film pressure balance (TFPB) technique using two different film holders, namely, the Scheludko-Exerowa cell and the porous plate. With the former, the equilibrium film thickness h at a given capillary pressure Pc and, with the latter, complete disjoining pressure versus thickness curves (Pi-h curves) were measured. Most of the results were obtained for 10(-4) and 10(-5) M beta-C12G2 solutions that contained 10(-3) M electrolyte. Measurements were carried out in a pH range from 3 to 9. The major results are the following: (1) For a given pH, a pronounced effect of the surfactant concentration cs is seen only if cs approximately cmc. This holds true for both low and high pH values. (2) For a given cs, at least one pronounced effect is seen if the pH is changed, namely a drop of the surface charge density down to zero when the isoelectric point (pH* and pHcr) is reached. (3) The pH of the isoelectric point increases with increasing surfactant concentration. (4) The q0-pH curve of beta-C12G2 shows two pH ranges (3-5.5 and 7-10) in which the surface charge density q0 is pH-insensitive, while a significant change of q0 was observed between pH=5.5 and 7.0. A possible explanation is given. PMID- 17279646 TI - In situ determination of the size and polydispersity of concentrated emulsions. AB - Droplet size distributions of concentrated, polydisperse oil-in-water emulsions have been measured using ultra small angle neutron scattering (USANS). The mean radii calculated by fitting a model for polydisperse hard spheres with excluded volume interactions to the USANS data were consistent with those derived from electroacoustics on diluted emulsions after correction for conductance behind the shear plane. The Porod radii measured by USANS were similarly consistent with the mean surface-area-weighted radii derived from electroacoustics, irrespective of the drop concentration or polydispersity. PMID- 17279647 TI - Polymorphism behavior of poly(ethylene naphthalate)/clay nanocomposites: role of clay surface modification. AB - The influence of clay surface modification on the polymorphism behavior of poly(ethylene naphthalate) (PEN)/clay nanocomposites was investigated via in situ Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction. The results show that untreated clay has a heterogeneous nucleating effect on PEN and favors the beta-crystal form, while the surfactant 1-hexadecyl-2,3-dimethylimidazolium (IMC16) has a plasticization effect and tends to enhance the kinetically favored alpha-phase instead. In contrast, the nanocomposite (PEN/IMC16-MMT) formed from IMC16-treated clay (IMC16-MMT) exhibits a strong temperature-dependent polymorphic behavior, with the beta-phase being more favored at 200 degrees C, but the alpha-phase being preferred instead at 180 degrees C. In situ FTIR spectroscopy of PEN/IMC16-MMT reveals an abrupt change in the concentration of alpha- and beta-"crystalline conformers" between the two temperatures during the induction period of crystallization. This is attributed to the hindered formation of stable nuclei at the organoclay surface. In addition, surfactant degradation gives rise to a highly plasticized polymer/organoclay interface. The combination of the hindered heterogeneous nucleation and plasticization effects gives rise to the unique temperature-dependent polymorphism behavior in PEN/IMC16-MMT. PMID- 17279648 TI - Interaction forces in thin liquid films stabilized by hydrophobically modified inulin polymeric surfactant. 2. Emulsion films. AB - The interaction forces in emulsion films stabilized using hydrophobically modified inulin (INUTEC SP1) were investigated by measuring the disjoining pressure of a microscopic horizontal film between two macroscopic emulsion drops of isoparaffinic oil (Isopar M). A special measuring cell was used for this purpose whereby the disjoining pressure Pi was measured as a function of the equivalent film thickness hw. The latter was determined using an interferometric method. In this way Pi-hw curves were established at a constant INUTEC SP1 concentration of 2x10(-5) mol.dm-3 and at various NaCl concentrations. At a constant disjoining pressure of 36 Pa, a constant temperature of 22 degrees C, and a film radius of 100 microm, hw decreased with an increase in the NaCl concentration, Cel, and reached a constant value of 11 nm at Cel=5x10(-2) mol.dm 3. This reduction in film thickness is due to the compression of the electrical double layer, and at the above critical NaCl concentration any electrostatic repulsion is removed and only steric interaction remains. This critical electrolyte concentration represents the transition from electrostatic to steric interaction. At a NaCl concentration of 2x10(-4) mol.dm-3 the Pi-hw isotherms showed a gradual decrease in hw with an increase in capillary pressure, after which there was a jump in hw from approximately 30 to approximately 7.2 nm when Pi reached a high value of 2-5.5 kPa. This jump is due to the formation of a Newton black film (NBF), giving a layer thickness of the polyfructose loops of approximately 3.6 nm. The film thickness did not change further when the pressure reached 45 kPa, indicating the high stability of the film. Pi-hw isotherms were obtained at various NaCl concentrations, namely, 5x10(-2), 5x10(-1), 1.0, and 2.0 mol.dm-3. The initial thicknesses are within the range 9-11 nm, after which a transition zone starts, corresponding to a pressure of about 0.5 kPa. In this zone all films transform to an NBF with a jump, after which the thickness remains constant with a further increase in the disjoining pressure up to 45 kPa, with no film rupture. This indicates the very high stability of the NBF in the presence of high electrolyte concentrations. The high emulsion film stability (due to strong steric repulsions between the strongly hydrated loops of polyfructose) is correlated with the bulk emulsion stability. PMID- 17279649 TI - Separation of fluoride from other monovalent anions using multilayer polyelectrolyte nanofiltration membranes. AB - Nanofiltration (NF) is an attractive technique for reducing F- concentrations to acceptable levels in drinking water, but commercial NF membranes such as NF 270 and NF 90 show minimal Cl-/F- selectivity. In contrast, simple layer-by-layer deposition of 4.5-bilayer poly(styrene sulfonate) (PSS)/poly(diallyldimethylammonium chloride) (PDADMAC) films on porous alumina supports yields NF membranes that exhibit Cl-/F- and Br-/F- selectivities>3 along with solution fluxes that are >3-fold higher than those of the commercial membranes. Fluoride rejection by (PSS/PDADMAC)4PSS membranes, which is >70%, is independent of pressure over a range of 3.6 to 6.0 bar, suggesting that the primary transport mechanism in these films is convection. Moreover, the fact that Br-/F- selectivity is 12% higher than Cl-/F- selectivity suggests that discrimination among the monovalent ions is based on size (Stokes radius). Chloride/fluoride selectivities are essentially constant over Cl-/F- feed ratios from 1 to 60, so these separations will be viable over a range of conditions. Interestingly, PSS/protonated poly(allylamine) films show little Cl-/F- selectivity, and the selectivity of PSS/PDADMAC membranes is a strong function of the number of deposited layers, indicating that NF properties are very sensitive to film structure. PMID- 17279650 TI - Water wetting transition parameters of perfluorinated substrates with periodically distributed flat-top microscale obstacles. AB - Superhydrophobicity is obtained on photolithographically structured silicon surfaces consisting of flat-top pillars after a perfluorosilanization treatment. Systematic static contact angle measurements were carried out on these surfaces as a function of pillar parameters that geometrically determine the surface roughness, including pillar height, diameter, top perimeter, overall filling factor, and disposition. In line with thermodynamics models, two regimes of static contact angles are observed varying each parameter independently: the "Cassie" regime, in which the water drop sits suspended on top of the pillars (referred to as composite), corresponding to experimental contact angles greater than 140-150 degrees, and the "Wenzel" regime, in which water completely wets the asperities (referred to as wetted), corresponding to lower experimental contact angles. A transition between the Cassie and Wenzel regimes corresponds to a set of well-defined parameters. By smoothly depositing water drops on the surfaces, this transition is observed for surface parameter values far from the calculated ones for the thermodynamic transition, therefore offering evidence for the existence of metastable composite states. For all studied parameters, the position of the experimental transition correlates well with a rough estimation of the energy barrier to be overcome from a composite metastable state in order to reach the thermodynamically favored Wenzel state. This energy barrier is estimated as the surface energy variation between the Cassie state and the hypothetical composite state with complete filling of the surface asperities by water, keeping the contact angle constant. PMID- 17279651 TI - Van der Waals dispersion forces between dielectric nanoclusters. AB - Various methods are evaluated for their ability to calculate accurate van der Waals (VDW) dispersion forces between nanoclusters. We compare results for spheres using several methods: the simple Hamaker two-body method, the Lifshitz (DLP) theory with the Derjaguin approximation, the Langbein result for spheres, and our "coupled dipole method" (CDM). The assumptions and shortcomings of each method are discussed. The CDM accounts for all n-body forces, does not assume a continuous and homogeneous dielectric function in each material, accounts for the discreteness of atoms in the particles, can be used for particles of arbitrary shape, and can exactly include the effects of various media. At present, the CDM does not account for retardation. It is shown that even for spheres, methods other than the CDM often give errors of 20% or more for VDW dispersion forces between typical dielectric materials. A related calculation for metals reveals an error in the Hamaker two-body result of nearly a factor of 2. PMID- 17279652 TI - Brownian dynamics simulations of polyelectrolyte adsorption onto charged patterned surfaces. AB - The adsorption of single polyelectrolyte molecules onto surfaces decorated with periodic arrays of charged patches was studied using Brownian dynamics simulations. A free-draining, freely jointed bead-rod chain was used to model the polyelectrolyte, and electrostatic interactions were incorporated using a screened Coulombic potential with the excluded volume accounted for by a hard sphere potential. The simulations predicted that the polyelectrolyte lies close to the adsorbing surface if the patch length, surface charge density, and screening length are sufficiently large. Chain conformations were found to be very sensitive to patch length, patch spacing, and the nature of the charge on adjacent patches. This is due both to the size of the polymer relative to patch length and spacing and to the structure of the electric field near the surface. In some cases, the component of the radius of gyration parallel to the surface can be made smaller than its free-solution value, which is contrary to what is observed for a uniformly charged surface. Isolated charged patches were also considered, and significant adsorption was observed above a critical surface charge density. The results demonstrate how polyelectrolyte conformations can be controlled by the design of the charged patches and may be useful for applications in which adsorbed polyelectrolyte films play a key role. PMID- 17279653 TI - Hydrogen-induced stress relaxation in thin Pd films: influence of carbon implementation. AB - The influence of carbon impurities on mechanical properties of thin Pd film in the process of hydride formation and its disintegration has been investigated "in situ" by means of atomic force microscopy (AFM). Pd interaction with hydrogen leads to the formation of hydride PdHx, if critical conditions of pressure and temperature are reached (equilibrium hydrogen pressure over PdHx at 298 K is approximately 1 kPa). The lattice constant of PdHx is larger than that of the original metal, and the hydride formation generates high stress within the film. As a consequence, the reversible formation of well organized mesoscopic protrusions on the film surface is observed. In this paper, we focus our investigation on the mechanical response which occurs when, prior to hydride generation, carbon atoms are incorporated into the bulk of the film. The systems characterized by carbon incorporation from the two opposite sides of thin palladium film (HOPG substrate and hydrocarbon fragments deposit from a gas-phase reached by preadsorption of ethylene) are compared. For both cases the mechanism of mechanical response is the same, but very different from that registered for pure thin palladium film. Carbon impurities induce, during PdHx decomposition, creation of an organized network of cracks which divides the continuous film into separated domains. The mechanisms of carbon introduction occurring in both cases have been proposed. PMID- 17279654 TI - Modeling the kinetics of gas adsorption in multilayer porphyrin films. AB - A kinetic model is proposed to describe the diffusion and adsorption behavior of gas in multilayer films. Numerical solutions are attained on time scales of seconds using a finite differencing approximation to the kinetic equations. Predictions of this model are compared to experimental data for the case of NO2 diffusing through a porphyrin film. The model predicts a binding energy for the NO2 porphyrin interaction of 0.72 eV. It also predicts that for this system diffusion is the limiting factor for the adsorption response time of the film, although the recovery time is determined by both the diffusion coefficient and NO2 binding energy. Comparison with experiment gives a predicted diffusion coefficient of approximately 10(-14) m2.s-1. PMID- 17279655 TI - Redox properties of vanadium ions in SBA-15-supported vanadium oxide: an FTIR spectroscopic study. AB - The state of vanadium ions in VxOy/SBA-15 (2.7 wt % V) was studied with FTIR spectroscopy using CO and NO as probe molecules. Neither CO (at 85 K) nor NO (at RT) adsorb on the oxidized sample because of the coordinative saturation of V5+ ions and the covalent character of the V5+=O bond. After treatment of the sample in 50 kPa H2 at 673 K, the V5+ ions are reduced to two different types of V3+ sites, as manifested by carbonyl bands at 2189 and 2177 cm-1. In the presence of O2 at 85 K, thus formed V3+ ions are partly oxidized to V4+ sites showing carbonylic bands at 2202 and 2190 cm-1. When the reduced sample is exposed to O2 at room temperature, the V3+ ions are fully oxidized to V5+. The adsorption of NO on the reduced VxOy/SBA-15 shows that the V3+ and V4+ ions possess two effective coordinative vacancies and as a result can adsorb two NO molecules forming the respective V3+(NO)2 and V4+(NO)2 dinitrosyls. The introduction of O2 to the VxOy/SBA-15-NO system leads to reoxidation of the V3+ and V4+ ions to V5+ and formation of bridged (1639 cm-1) and bidentate (1573 cm-1) surface nitrates. After coadsorption of CO and NO on the reduced sample the formation of surface mixed carbonyl-nitrosyls (2108 and 1723 cm-1) was observed for the first time. PMID- 17279656 TI - Detection of novel gaseous states at the highly oriented pyrolytic graphite-water interface. AB - We report a novel form of the gaseous state at the interface of water and highly oriented pyrolytic graphite (HOPG) that is induced by local supersaturation of gas. Such local supersaturation of gas next to the HOPG substrate can be achieved by (1) displacing an organic liquid with a gentle flow of water, (2) displacing cold water (approximately 0 degrees C) with a gentle flow of warm water (approximately 40 degrees C), or (3) preheating the HOPG substrate to approximately 80 degrees C before exposing it to water at room temperature. In addition to the spherical-cap-shaped nanobubbles reported by many researchers, flat (quasi-two-dimensional, pancake-like) gas layers and nanobubble-flat gas layer composites (spherical-cap-shaped nanobubbles sitting on top of the quasi two-dimensional gas layers) were detected. These entities disappeared after the system was subjected to a moderate level of degassing (approximately 0.1 atm for 1.5 h), and they did not form when the liquids involved in the aforementioned displacing procedure (to induce local supersaturation of gas) had been predegassed (to approximately 0.1 atm). The stability and some physical properties of these newly found gaseous states are examined. PMID- 17279657 TI - Adsorption of N-Decyl-N,N,N-trimethylammonium triflate (DeTATf), a cationic surfactant, on the Au(111) electrode surface. AB - The adsorption behavior of the cationic surfactant N-decyl-N,N,N trimethylammonium triflate (DeTATf) on the Au(111) electrode surface was characterized using cyclic voltammetry, differential capacity, and chronocoulometry. The thermodynamics of the ideally polarized electrode have been employed to determine the Gibbs excess and the Gibbs energy of adsorption. The results show that the adsorption of DeTATf has a multistate character. At low bulk DeTATf concentrations, the adsorption state is consistent with the formation of an adsorbed film of nearly flat molecules. At higher concentrations this film may represent a three-dimensional aggregated state. At negative potentials and charge densities close to 0 microC cm-2, the data suggest the formation of a film of tilted molecules oriented with the hydrocarbon tail toward the metal surface and the polar head toward the solution. A surprising result of this study is that DeTATf displays adsorption characteristics of a zwitterionic rather than a cationic surfactant. This behavior indicates that the adsorbed species is an ion pair. PMID- 17279658 TI - Stability and disintegration of ultrathin heptane films in water: molecular dynamics simulations. AB - Molecular dynamics simulations of ultrathin heptane films (less than 5 nm in thickness) in water were conducted to study their stability and disintegration behavior. The density distributions of heptane and water molecules across the film were determined for different equilibrium film thicknesses ranging from 1.5 to 4 nm. The potential energy of the system was computed as a function of the heptane number fraction, and the results were employed to determine the excess energy of mixing of heptane in water. The diffusion coefficients of heptane and water obtained from the MD simulations were also compared with experimental data. A good agreement was found between the heptane self-diffusivity obtained from the MD simulations and its literature reported value. Following an analysis of the equilibrium properties of the heptane films and associated structures, we performed simulations where the shapes of the heptane films were initially perturbed. Different perturbations of these ultrathin films led to formation of various associated structures, including cylindrical rodlike heptane droplets, films with holes, and intact films. The different shapes are formed in systems with the same heptane/water composition. An analysis of this behavior is presented showing the possibility of multiple associated structures with similar total energy in these highly confined systems. PMID- 17279659 TI - Spectroscopic characterization and Langmuir-Blodgett films of a novel azopolymer material. AB - Spectroscopic characterization and fabrication of Langmuir and Langmuir-Blodgett (LB) films of an azopolymer-pyridine (PAzPy) are reported. UV-visible absorption and fluorescence spectra, Fourier transform infrared (FTIR) spectra, and Raman spectra were recorded. The vibrational assignment of the observed spectra is supported by a complete geometry optimization, followed by vibrational frequency and intensity computations of both the trans and cis forms of the monomer (AzPy) using density functional theory at the B3LYP 6-31G(d,p) level of theory. Langmuir monolayers of the polymer (PAzPy) were formed at the water-air interface, and LB films of high quality were formed onto solid substrates. The polymer LB films were investigated by surface-enhanced Raman scattering. PMID- 17279660 TI - Fabrication of a molecular-level multilayer film on organic polymer surfaces via chemical bonding assembly. AB - A fresh multilayer film was fabricated on a molecular level and successfully tethered to the surface of a hydroxylated organic substrate via chemical bonding assembly (CBA). Sulfate anion groups (SO4-) were preintroduced onto the surface of biaxially oriented polypropylene (BOPP) films via a reference method. Upon hydrolysis of the SO4- groups, hydroxyl groups (--OH) were formed that subsequently acted as initial reagents for a series of alternate reactions with terephthalyl chloride (TPC) and bisphenol A (BPA). A stable and well-defined multilayer film was thus fabricated via the CBA method. As a result of the nanoscale multilayer fresh film being abundant with reactive groups, it is believed that the film and its fabrication method should provide a fundamental platform for further surface functionalization and direct the design of advanced materials with desired properties. PMID- 17279662 TI - Effect of substituent position in coumarin derivatives on the interfacial assembly: reversible photodimerization and supramolecular chirality. AB - The Langmuir and Langmuir-Schaefer (LS) films of two coumarin derivatives, 4 octadecyloxylcoumarin (4-CUMC18) and 7-octadecyloxylcoumarin (7-CUMC18), were newly synthesized, and their interfacial assemblies were investigated. Owing to the different substituent position of the long octadecyloxy chain in the coumarin parent, the two compounds showed completely different behaviors in the interfacial assemblies. When they were spread at the air/water interface, 7 CUMC18 formed a monolayer while 4-CUMC18 formed a multilayer film on the water surface. The spreading films on the water surface were transferred onto solid substrates by a Langmuir-Schaefer method, and the transferred films were characterized by UV-vis, Fourier transfer infrared, X-ray diffraction, circular dichroism, and atomic force microscopy spectra. Different packing of the molecules in the multilayer films was observed. While coumarin groups stacked in a face-to-face way in 7-CUMC18 film, they stacked in a head-to-tail manner in 4 CUMC18 film. Furthermore, distinct properties of the multilayer films were observed. It is revealed that a reversible [2+2] photodimerization and photocleavage could be induced in the LS film of 7-CUMC18 under photoirradiation with UV light of 365 and 254 nm, respectively. No photodimerization occurred in the 4-CUMC18 film. However, the film of 4-CUMC18 showed a supramolecular chirality although the compound itself is achiral. PMID- 17279661 TI - On the dissolution of vapors and gases. AB - The captive bubble technique in combination with axisymmetric drop shape analysis (ADSA-CB) and with micro gas chromatography is used to study the dynamics of dissolution of different gases and vapors in water in situ. The technique yields the changes in the interfacial tension and bubble volume and surface. As examples, the dissolution of methanol and hexane vapors, inhaled anesthetic vapors, and gases, that is, diethyl ether, chloroform, isoflurane, enflurane, sevoflurane, desflurane, N2O, and xenon, and as nonimmobilizers perfluoropentane and 1,1,2-trichloro-1,2,2-trifluoro-ethane (R113) were investigated. The examination of interfacial tension-time and bubble volume-time functions permits us to distinguish between water-soluble and -insoluble substances, gases, and vapors. Vapors and gases generally differ in terms of the strength of their intermolecular interactions. The main difference between dissolution processes of gases and vapors is that, during the entire process of gas dissolution, no surface tension change occurs. In contrast, during vapor dissolution the surface tension drops immediately and decreases continuously until it reaches the equilibrium surface tension of water at the end of dissolution. The results of this study show that it is possible to discriminate anesthetic vapors from anesthetic gases and nonimmobilizers by comparing their dissolution dynamics. The nonimmobilizers have extremely low or no solubility in water and change the surface tension only negligibly. By use of newly defined molecular dissolution/diffusion coefficients, a simple model for the determination of partition coefficients is developed. PMID- 17279663 TI - Effect of vacuum annealing on the surface chemistry of electrodeposited copper(I) oxide layers as probed by positron annihilation induced auger electron spectroscopy. AB - Vacuum anneal induced changes in the surface layers of electrodeposited copper(I) oxide (Cu2O) were probed by time-of-flight positron annihilation induced Auger electron spectroscopy (TOF-PAES) and by electron induced Auger electron spectroscopy (EAES). Large changes in the intensity of the Cu PAES intensity resulting from isochronal in situ vacuum anneals made at increasing temperatures indicated that, before thermal treatment, the surface was completely covered by a carbonaceous overlayer and that this layer was removed, starting at a temperature between 100 and 200 degrees C, to expose an increasing amount of Cu in the top layer as the anneal temperature was increased. The thickness of this overlayer was estimated to be approximately 4 A based on analysis of the EAES data, and its variation with the thermal anneal temperature was mapped. This study demonstrated the order-of-magnitude enhancement in the sensitivity of PAES to the topmost surface layer in Cu2O relative to the EAES counterpart; factors underlying this contrast are discussed. Finally, the implications of ultrathin carbon layers on semiconductor surfaces are discussed. PMID- 17279665 TI - The movement of a water droplet on a gradient surface prepared by photodegradation. AB - A hydrophobic to hydrophilic gradient surface was prepared using the tuned photodegradation of an alkylsilane self-assembled monolayer (SAM) using irradiation of vacuum ultraviolet light (wavelength=172 nm). The water contact angle on the photodegraded SAM surface was adjusted using the intensity and time photoirradiation parameters. The formation of a gradient was confirmed by fluorescent labeling. The water drop moved from the hydrophobic to hydrophilic surface with a velocity that depended on the gradient. The higher the gradient, the faster the water moved. For the first time, we have prepared a gradient surface using photodegradation where the movement of a water drop was regulated by the degree of gradation. Considering that the photodegradation technique can be applied to various surfaces and to lithography, this technique will be useful for various material surfaces. PMID- 17279664 TI - Monte Carlo simulations of Lennard-Jones nonionic surfactant adsorption at the liquid/vapor interface. AB - We present Monte Carlo simulations of nonionic surfactant adsorption at the liquid/vapor interface of a monatomic solvent. All molecules in the system, solvent and surfactant, are characterized by the Lennard-Jones (LJ) potential using differing interaction parameters. Surfactant molecules consist of an amphiphilic chain with a solvophilic head and a solvophobic tail. Adjacent atoms along the surfactant chain are connected by finitely extensible harmonic springs. Solvent molecules move via the Metropolis random-walk algorithm, whereas surfactant molecules move according to the continuum configurational bias Monte Carlo (CBMC) method. We generate quantitative thermodynamic adsorption and surface tension isotherms in addition to surfactant radius of gyration, tilt angles, and potentials of mean force. Surface tension simulations compared to those calculated from the simulated adsorbed amounts and the Gibbs adsorption isotherm agree confirming equilibrium in our simulations. We find that the classical Langmuir isotherm is obeyed for our LJ surfactants over the range of head and tail lengths studied. Although simulated surfactant chains in the bulk solution exhibit random orientations, surfactant chains at the interface orient roughly perpendicular and the tails elongate compared to bulk chains even in the submonolayer adsorption regime. At a critical surfactant concentration, designated as the critical aggregation concentration (CAC), we find aggregates in the solution away from the interface. At higher concentrations, simulated surface tensions remain practically constant. Using the simulated potential of mean force in the submonolayer regime and an estimate of the surfactant footprint at the CAC, we predict a priori the Langmuir adsorption constant, KL, and the maximum monolayer adsorption, Gammam. Adsorption is driven not by proclivity of the surfactant for the interface, but by the dislike of the surfactant tails for the solvent, that is by a "solvophobic" effect. Accordingly, we establish that a coarse-grained LJ surfactant system mimics well the expected equilibrium behavior of aqueous nonionic surfactants adsorbing at the air/water interface. PMID- 17279666 TI - Spectral properties of rhodamine 3B adsorbed on the surface of montmorillonites with variable layer charge. AB - Montmorillonite was thermally treated at several temperatures to reduce the charge density of its layer surface. Absorption and fluorescence (steady-state and time-resolved) spectroscopies are now applied to study the adsorption of rhodamine 3B (R3B) laser dye in reduced charge montmorillonites (RCMs) in aqueous suspensions. The decrease in the charge density increases the intermolecular distance between adsorbed R3B molecules, reducing the tendency of the dye to self associate. H-type and J-type aggregates of R3B in RCMs are spectroscopically characterized, the fluorescent J-aggregates being more extensively formed by decreasing the charge density. Both the reduction in the dye aggregation and the formation of J-type aggregates enhance the fluorescence efficiency of R3B dye adsorbed in montmorillonite particles. Absorption with linearly polarized light reveals that the H-aggregates are more disposed toward the perpendicular of the clay surface than the monomer and J-aggregates species. PMID- 17279667 TI - Surface-enhanced resonance Raman scattering of cytochrome P450-2D6 on coated silver hydrosols. AB - Surface-enhanced resonance Raman scattering (SERRS) from dilute solutions (down to nanomolar concentrations) of human mono-oxygenase CYP2D6 is observed using aqueous dispersions of Ag nanoparticles (hydrosol) coated with self-assembled monolayers (SAMs) of mercaptoalkanoic acids of two different lengths. From a direct comparison with its resonance Raman spectrum in solution, CYP2D6 appears to fully retain its native structure upon adsorption on coated hydrosol through electrostatic interaction, while a structural change in the active site is observed when uncoated citrate-reduced hydrosol is used. Using SERRS on these biocompatible coated hydrosols, the effects of dextromethorphan on the enzyme's active site can be observed, demonstrating that CYP2D6 ability of binding substrates is preserved. Moreover, by tuning the wavelength of the exciting laser away from the main absorption band of the heme, the vibrational bands of the SAM coating are observed and analyzed to see how the presence of the protein affects the SAM structure. PMID- 17279668 TI - Retention forces of a liquid slug in a rough capillary tube with symmetric or asymmetric features. AB - On surfaces with asymmetric "sawtooth" features, liquid slugs or drops tend to move preferentially in one direction. In this theoretical study, the imbalance of capillary forces that leads to directionally biased wetting is examined. Capillary tubes with symmetric and asymmetric sawtooth features were used to estimate the ratios of retention forces in opposing directions. Our analysis suggests that the difference between the retention force in one direction versus the other can be maximized by increasing feature asymmetry and minimizing inherent hysteresis of the materials of construction. This work has implications for small channels or surfaces of fluid-handling components found in microfluidic devices and fuel cells. PMID- 17279669 TI - Catalysis of aryl ester hydrolysis in the presence of metallomicelles containing a copper(II) diethylenetriamine derivative. AB - The novel metallosurfactant Cu(II)-1-tetradecyldiethylenetriamine (Cu(II)TDET) was prepared, and the hydrolyses of 2-acetoxy-5-nitrobenzoic acid (1), 4-acetoxy 3-nitrobenzoic acid (2), 4-nitrophenyl acetate (3), and 2-nitrophenyl acetate (4) in the presence of micellar Cu(II)TDET were examined. The rate of ester hydrolysis for the series followed the order 1 approximately 2>3>4. The larger observed rate (kpsi) for 1 and 2 was attributed to (i) electrostatic interaction between the carboxylate anion and the cationic metallomicelle surface and (ii) the formation of a ternary complex metal:surfactant ligand:substrate (MLnS). The position of the carboxylate anion in the substrate did not significantly affect catalysis. Similar rates were observed when the carboxylate anion was ortho to the acyl ester 1 or para to the reaction center 2. The absence of a significant difference may be associated with the ternary complex coordination geometry, which unfavorably aligned the ligated substrate and the metal-bound hydroxyl. Mixed micellar solutions containing Cu(II)TDET and MTAB or Triton X-100 were examined. Added cosurfactants have a pronounced effect on the catalytic activity of Cu(II)TDET. At a low concentration of Cu(II)TDET the addition of MTAB or Triton X-100 increased the pseudo-first-order rate constant (kpsi) for the hydrolysis of 1 and 3 relative to the rate in pure Cu(II)TDET. The addition of a cosurfactant increased the total micellar volume (VM), promoting substrate incorporation within the pseudophase. At higher metallosurfactant concentration, the rate enhancement was smaller due to the dilution of the substrate within the co-micellar pseudophase. PMID- 17279671 TI - Ordering by collapse: formation of bilayer and trilayer crystals by folding Langmuir monolayers. AB - Neutron and synchrotron X-ray studies of arachidic-acid monolayers compressed to the collapse region, beyond their densely packed molecular area, reveal that the resulting structures exhibit a surprising degree of reproducibility and of order. The structure of the collapsed monolayers differs for films that are spread on pure water or on CaCl2 solutions. On pure water, the collapsed monolayer forms a stable crystalline trilayer structure, with acyl-chain in-plane packing practically identical to the three-dimensional (3D) crystal structure of fatty acids. For monolayers spread on Ca2+ solutions, the collapsed film consists of a bi- and trilayer mixture with a ratio that changes by the collapse protocol. Our analysis suggests that the bilayer structure is inverted, i.e., with the hydrophobic tails in contact with the water surface and the calcium ions bridging the polar heads. The inverted bilayer structure possesses a well-ordered crystalline slab of calcium oxalate monohydrate intercalated between two acyl chains. We provide theoretical arguments rationalizing that the observed structures have lower free energies compared with other possible structures and contend that the collapsed structures may, under certain circumstances, form spontaneously. PMID- 17279670 TI - Temperature-dependent phase behavior and the crystal-forming nucleation process of ethyl 4-fluoro-2,3-dihydroxystearate monolayers. AB - The phase behavior of enantiomeric compounds as well as mixtures of enantiopure and racemic diastereomers of ethyl 4-fluoro-2,3-dihydroxystearates has been investigated using surface pressure-area isotherms and Brewster angle microscopy (BAM). All mixtures exhibit a small plateau region within the surface pressure area isotherm at 20 degrees C, whereas the enantiopure compound shows an isotherm behavior similar to that of fatty acids. Corresponding to the film balance measurements, the BAM images demonstrate different shapes of the domains within the coexistence region of the liquid-condensed/liquid-expanded phase. The domain structures of the monolayers were visualized after Langmuir-Blodgett transfer on mica sheets by scanning force microscopy (SFM). From the SFM images it becomes obvious that small crystallites are formed for all investigated compounds; however, their molecular assembly is diverse for different enantiomers. Variations in the phase behavior can be correlated with interactions between the polar molecular moieties and the subphase and altered intermolecular interactions. Molecular modeling calculations were applied to elucidate the structural organization of these intermolecular interactions. Ab initio calculations of the minima conformers of (S,S,R)- and (S,S,S)-ethyl 4-fluoro-2,3 dihydroxystearates have been performed to predict with the HARDPACK program the two-dimensional lattice structure based on the P1 space group. These calculations showed that intermolecular hydrogen bridges are crucial for the interactions within and between the molecules. PMID- 17279672 TI - Influence of the polyelectrolyte molecular weight on exponentially growing multilayer films in the linear regime. AB - Alternated deposition of polyanions and polycations on a charged solid substrate leads to the buildup of polyelectrolyte multilayer (PEM) films. Two types of PEM films were reported in the literature: films whose thickness increases linearly and films whose thickness increases exponentially with the number of deposition steps. However, it was recently found that, for exponentially growing films, the exponential increase of the film thickness takes place only during the initially deposited pairs of layers and is then followed by a linear increase. In this study, we investigate the growth process of hyaluronic acid/poly(L-lysine) (HA/PLL) and poly(L-glutamic acid)/poly(allylamine) (PGA/PAH) films, two films whose growth is initially exponential, when the growth process enters the linear regime. We focus, in particular, on the influence of the molecular weight (Mw) of the polyelectrolytes. For both systems, we find that the film thickness increment per polyanion/polycation deposition step in the linear growth regime is fairly independent of the molecular weights of the polyelectrolytes. We also find that when the (HA/PLL)n films are constructed with low molecular weight PLL, these chains can diffuse into the entire film during each buildup cycle, even for very thick films, whereas the PLL diffusion of high molecular weight chains is restricted to the upper part of the film. Our results lead to refinement of the buildup mechanism model, introduced previously for the exponentially growing films, which is based on the existence of three zones over the entire film thickness. The mechanism no longer needs all the "in" and "out" diffusing polyanions or polycations to be involved in the buildup process to explain the linear growth regime but merely relies on the interaction between the polyelectrolytes with an upper zone of the film. This zone is constituted of polyanion/polycation complexes which are "loosely bound" and rich in the polyelectrolyte deposited during the former deposition step. PMID- 17279673 TI - Structural characterization of 4-bromostyrene self-assembled monolayers on si(111). AB - Organic functionalization of silicon holds promise for a variety of applications ranging from molecular electronics to biosensing. Because the performance and reliability of organosilicon devices will be intimately tied to the detailed structure of the organic adlayers, it is imperative to develop systematic strategies for forming and characterizing self-assembled monolayers (SAMs) on silicon with submolecular spatial resolution. In this study, we use 4 bromostyrene for the photochemical growth of Br-terminated SAMs on Si(111). A variety of experimental and theoretical techniques including atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), X-ray reflectivity (XRR), X-ray standing waves (XSW), X-ray fluorescence (XRF), and density functional theory (DFT) have been employed to determine the coverage and conformation of the 4-bromostryene molecules within the SAM. In particular, AFM verifies a continuous and atomically flat SAM, and the XRR data indicate a SAM thickness of 8.50 A and a molecular coverage of 46% of the surface silicon atoms. Because the DFT calculations indicate a molecular length of 8.89 A, the measured XRR thickness implies a molecular tilt angle of approximately 17 degrees. The XRR analysis also suggests that the Br atoms are preserved on top of the SAM in agreement with XPS measurements that show bromine bound solely to carbon and not to silicon. XRF reveals a Br atomic coverage of 50%, again in close agreement to that found by XRR. Single-crystal Bragg diffraction XSW is used to generate a three-dimensional map of the Br distribution within the SAM, which in conjunction with the XRR result suggests that the 4-bromostyrene molecules are tilted such that the Br atoms are located over the T4 sites at a height of 8.50 A above the top bulklike Si(111) layer. The direction of molecular tilt toward the T4 sites is consistent with that predicted by the DFT calculation. Overall, through this unique suite of complementary structural characterization techniques, it is concluded that the Br functional handle is preserved at the top of the SAM and is available for further substitutional chemistry. PMID- 17279674 TI - Organic thin film formation using asymmetric surface-active viologens. AB - In the present study, asymmetric surface-active viologens were applied successfully for the thin film formation of organic pigments using the immersion plating technique. The influences of the hydrophobicity of the surfactants and the pH of the plating solution on the film formation were investigated. In addition, the interfacial chemistry and electrochemistry of the surfactants were studied, and the mechanism of the film formation has been proposed and discussed. PMID- 17279675 TI - Langmuir-Blodgett films of a cationic zinc porphyrin-imidazole-functionalized fullerene dyad: formation and photoelectrochemical studies. AB - Electron donor-acceptor dyad ensembles of a water-soluble cationic zinc porphyrin (viz., zinc tetrakis(N-methylpyridinium)porphyrin tetrachloride, Zn(TMPyP)) and a C60 derivative that bears an imidazole ligand (viz., 2 (phenylimidazolyl)fulleropyrrolidine, C60im) were assembled during the formation of Langmuir and then Langmuir-Blodgett (LB) films. Surface pressure versus surface area isotherms and surface pressure time profiles, as well as Brewster angle microscopic images documented that the Langmuir films formed were remarkably stable. Subsequently, these Langmuir films were transferred onto different solid substrates, by using the LB technique, for spectroscopic and photoelectrochemical characterization. The UV-vis spectroscopic investigations confirmed that the water-soluble Zn(TMPyP) was, indeed, transferred together with C60im in the LB films. Upon visible light illumination of these LB films, deposited on the ITO transparent conductive supports, a photocurrent generated in the C60im-Zn(TMPyP) system is ascribed to an efficient photoinduced electron transfer from the electron donor, porphyrin singlet excited-state to the electron acceptor, C60. Overall, internal photon-to-current efficiency, IPCE, of the photoanodic current generation (with ascorbate as a sacrificial electron donor) in the ITO/C60im-Zn(TMPyP)/ascorbate/Pt construct is over 5x larger than that of the photocathodic system (with methyl viologen, MV2+, as a sacrificial electron acceptor) in the ITO/Zn(TMPyP)-C60im/MV2+/Pt construct. Highly ordered film stacking favors vectorial electron transfer within the dyad, giving rise to the highest IPCE values of 2.5% determined for a photoanode that was composed of around 20 monolayer films. PMID- 17279676 TI - Photoinduced amphiphilic property of InNbO4 thin film. AB - An InNbO4 thin film was prepared by a sol-gel method. The photoinduced amphiphilic (hydrophilic and lipophilic) property on the film was determined from the changes in contact angles for water and diiodomethane (CH2I2) under light (lambda>300 nm) irradiation. Before light irradiation, the contact angles for water and diiodomethane were approximately 50 degrees and 40 degrees, respectively. Subsequently, light irradiation induced the contact angles to decrease. The critical contact angles for water and diiodomethane were approximately 0 degrees and 15 degrees, respectively, suggesting that this film possesses the photoinduced superhydrophilic and amphiphilic properties. This is the first report of a complex oxide with a photoinduced amphiphilicity. In the photoinduced amphiphilic conversion process, it was also found that both the total gas-solid surface free energy and the gas-solid surface free energy of the polar component increased. PMID- 17279677 TI - Monomer adsorption on equilateral triangular lattices with repulsive first neighbor interactions. AB - A model of monomer adsorption on infinitely long, finite-width M equilateral triangular lattices with nonperiodic boundaries is presented. The study includes adsorbate-adsorbate first- and second-neighbor interactions with results obtained for repulsive first neighbors. The matrix method and numerical algorithms presented here allow determination of the occupational characteristics of the adsorption crystallization phases, which fit exact analytic expressions in the width M of the lattice. The limit as M approaches infinity provides the complete energy phase diagram for the infinite two-dimensional surface and recovers the results obtained by different methods that were often applied only in restricted energy regions of the phase diagram. The ordered phases are (2x1), (2x2), (3x1), (square root of 3xsquare root of 3) R30 degrees, and the complementary phases of (2x2) and (square root of 3xsquare root of 3) R30 degrees. Comparison is made with other theoretical studies and with experimental observations on adsorption systems consistent with the limitations of the model. In some cases, comparison with experimental data yields bounds on the interaction energies between adsorbates. On the basis of the model, suggestions are made on the manner in which to conduct relatively low temperature experiments to allow determination of most, if not all, of the interaction energies from the knowledge of the sequences of phases and the conditions prevailing at the transitions between phases. PMID- 17279678 TI - The antioxidant tempamine: in vitro antitumor and neuroprotective effects and optimization of liposomal encapsulation and release. AB - The piperidine nitroxide tempamine (TMN) is a cell-permeable, stable radical having antioxidant, anticancer, and proapoptotic and/or pronecrotic activities, as was demonstrated by us in cell cultures. We also demonstrated synergism between TMN and doxorubicin in doxorubicin-sensitive and doxorubicin-resistant cell lines. Treatment of the C26 mouse colon carcinoma model in vivo also demonstrated synergism between TMN and doxorubicin in sterically stabilized liposomes (SSLs) containing TMN (SSL-TMN) and those containing doxorubicin. The above effects of TMN and SSL-TMN motivated us to develop and optimize the SSL-TMN formulation so that it will be able to reach the disease site with a sufficiently high TMN level and a release rate needed to achieve a therapeutic effect. Because TMN is an amphipathic weak base, it was remote loaded by an intraliposome high/extraliposome low transmembrane ammonium sulfate gradient. The kinetics and level of TMN loading were monitored by cyclic voltammetry (CV) and electron paramagnetic resonance (EPR); the latter also indicates TMN precipitation in the intraliposomal aqueous phase. The regeneration of the original CV and EPR signals by the ionophore nigericin indicates that TMN remained fully intact during loading and release. The cardinal role of the transmembrane ammonium ion gradient in the loading process was proven by the use of the selective ionophores nonactin (for NH4+) and nigericin (for H+). The anion of the ammonium salts affects loading stability and the rate of TMN release, both mediated through the TMN state of aggregation in the intraliposomal aqueous phase. The greater the TMN salt precipitation, the slower the TMN release rate. This was supported by measurement of osmolality, which is inversely related to TMN salt precipitate. Precipitation is in the order SO4(-2)>Cl-1>glucuronate-1. Liposome lipid composition, magnitude of the transmembrane ammonium ion gradient, and type of anion of the ammonium salt determine the amount of TMN loaded and its release rate. PMID- 17279679 TI - Adsorption kinetics of bovine serum albumin on fused silica: population heterogeneities revealed by single-molecule fluorescence microscopy. AB - The adsorption of bovine serum albumin (BSA) on fused silica at neutral pH was investigated at the single-molecule level by total internal reflection fluorescence microscopy. Dye-labeled BSA molecules that adsorbed on the quartz surface lit up as discrete, fluorescent dots which eventually disappeared upon desorption. Movies of these events offered unprecedented details for kinetics modeling. The results suggested that 99.3% of the BSA was not sticky, and even if adsorbed, it would desorb in minutes. In contrast, the remaining 0.7% was not only sticky, but would anchor in due course. Such population heterogeneity, otherwise masked in ensemble measurements, sheds new light on our understanding of protein adsorption. The methodology is also generally applicable to the studies of macromolecules at interfaces. PMID- 17279680 TI - Adsorption of fluorinated ethers and alcohols on fresh and oxidized carbon overcoats for magnetic data storage. AB - Temperature programmed desorption has been used to study the desorption kinetics and desorption energies of perfluorodiethylether, (CF3CF2)2O, and 2,2,2 trifluoroethanol, CF3CH2OH, adsorbed on fresh and oxidized hydrogenated amorphous carbon (a-CHx) films. (CF3CF2)2O and CF3CH2OH serve as models for the ether backbone and hydroxyl end-groups of Fomblin Zdol, the lubricant most commonly used to lubricate the surfaces of amorphous carbon overcoats on magnetic data storage hard disks. Our measurements clearly reveal, for the first time, the effects of surface oxidation on the adsorption of fluorocarbon lubricants such as Fomblin Zdol on a-CHx films. Oxidation of the a-CHx surface increases the desorption energy of CF3CH2OH but has no observable impact on the desorption energy of (CF3CF2)2O. These results support the suggestion that the alcohols interact with the surface via hydrogen bonding. From a practical perspective, these results imply that the oxidation of the fresh a-CHx film may serve as a means to control or tailor the a-CHx surface to optimize the properties of the lubricant-overcoat interface in hard disks. PMID- 17279681 TI - Evaluation of the interaction of propranolol with 1,2-dimyristoyl-sn-glycero-3 phosphocholine (DMPC) liposomes: the partitioning model. AB - The sorption behavior of the amine containing beta-receptor blocking agent propranolol (Ppn) in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles was investigated. Both protonated and unprotonated Ppn were measured in the continuous phase after removal of the vesicles containing sorbed Ppn by centrifugation. In contrast, by analyzing the surface charge density, deduced from electrophoretic mobility measurements, only the sorbed protonated Ppn was determined. A partitioning model was used to describe the sorption behavior. Sensitivity analysis revealed that sufficiently reliable and independent parameters were obtained. The partition coefficient of the unprotonated Ppn was about 22 times higher than that of the protonated analogue. Statistical analysis revealed a significant increase in the intrinsic partition coefficients of both Ppn analogues with an increase in the salt concentration. PMID- 17279682 TI - Preparation of organic nanoparticles using microemulsions: their potential use in transdermal delivery. AB - Organic nanoparticles of cholesterol and retinol have been synthesized in various AOT (Aerosol OT; sodium bis(2-ethylhexyl) sulfosuccinate)/heptane/water microemulsions by direct precipitation of the active principle in the aqueous cores. The nanoparticles are observed by transmission electron microscopy (TEM) using the adsorption of a contrasting agent, such as iodine vapor. The size of the nanoparticles can be influenced, in principle, by the concentration of the organic molecules and the diameter of the water cores, which is related to the ratio R=[H2O]/[surfactant]. The particles remain stable for several months. The average diameter of the cholesterol nanoparticles varies between 3.0 and 7.0 nm, while that of retinol varies between 4.0 and 10 nm. The average size of the cholesterol nanoparticles does not change much either as a function of the ratio R or as a function of the concentration of cholesterol. The constant size of the nanoparticles can be explained by the thermodynamic stabilization of a preferential size of the particles. Chloroform is used to carry the active principle into the aqueous cores. Retinol molecules form J-complexes composed of two or three molecules, as detected by UV-visible spectroscopy. PMID- 17279684 TI - Immobilized horseradish peroxidase as a reusable catalyst for emulsion polymerization. AB - The study on the adsorption of horseradish peroxidase (HRP) onto silicon wafers was carried out by means of in situ ellipsometry, atomic force microscopy (AFM) and contact angle measurements. A smooth HRP layer adsorbed onto Si wafers. The enzymatic activity of free or adsorbed HRP was determined by the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and by the emulsion polymerization of ethylene glycol dimethacrylate (EGDMA). Upon adsorbing, HRP molecules might have undergone some conformational changes, which caused a small reduction of enzymatic activity in comparison to that observed for HRP solution. However, it was possible to reuse the same HRP-covered Si wafer as catalyst in the polymerization of EGDMA three times. PMID- 17279683 TI - Long-term exposure to CdTe quantum dots causes functional impairments in live cells. AB - Several studies suggested that the cytotoxic effects of quantum dots (QDs) may be mediated by cadmium ions (Cd2+) released from the QDs cores. The objective of this work was to assess the intracellular Cd2+ concentration in human breast cancer MCF-7 cells treated with cadmium telluride (CdTe) and core/shell cadmium selenide/zinc sulfide (CdSe/ZnS) nanoparticles capped with mercaptopropionic acid (MPA), cysteamine (Cys), or N-acetylcysteine (NAC) conjugated to cysteamine. The Cd2+ concentration determined by a Cd2+-specific cellular assay was below the assay detection limit (<5 nM) in cells treated with CdSe/ZnS QDs, while in cells incubated with CdTe QDs, it ranged from approximately 30 to 150 nM, depending on the capping molecule. A cell viability assay revealed that CdSe/ZnS QDs were nontoxic, whereas the CdTe QDs were cytotoxic. However, for the various CdTe QD samples, there was no dose-dependent correlation between cell viability and intracellular [Cd2+], implying that their cytotoxicity cannot be attributed solely to the toxic effect of free Cd2+. Confocal laser scanning microscopy of CdTe QDs-treated cells imaged with organelle-specific dyes revealed significant lysosomal damage attributable to the presence of Cd2+ and of reactive oxygen species (ROS), which can be formed via Cd2+-specific cellular pathways and/or via CdTe-triggered photoxidative processes involving singlet oxygen or electron transfer from excited QDs to oxygen. In summary, CdTe QDs induce cell death via mechanisms involving both Cd2+ and ROS accompanied by lysosomal enlargement and intracellular redistribution. PMID- 17279685 TI - Formation of single-crystalline aragonite tablets/films via an amorphous precursor. AB - Thin tablets and films of calcium carbonate have been grown at the air-water interface via an amorphous precursor route using soluble process-directing agents and a Langmuir monolayer based on resorcarene. By using appropriate concentrations of poly(acrylic acid-sodium salt) in combination with Mg2+ ion, an initially amorphous film is deposited on the monolayer template, which subsequently crystallizes into a mosaic film composed of a mixture of single crystalline and spherulitic patches of calcite and aragonite. Of particular importance is the synthesis of single-crystalline "tablets" of aragonite (approximately 600 nm thick), because this phase generally forms needle-like polycrystalline aggregates when grown in vitro. To our knowledge, a tabular single-crystalline morphology of aragonite has only been observed in the nacreous layer of mollusk shells. Therefore, this in vitro system may serve as a useful model for examining mechanistic issues pertinent to biomineralization, such as the influence of organic templates on nucleation from an amorphous phase. PMID- 17279686 TI - Preparation of protein-silicate hybrids from polyamine intercalation of layered montmorillonite. AB - Hybrids of the model BSA protein and layered silicate clay with d spacing of approximately 62 A were prepared from either direct or stepwise intercalation. The pristine montmorilloinite (Na+-MMT) was first modified by poly(oxyalkylene) amine salts (POP- and POE-amine) of 2000 g/mol Mw to a gallery-expanded silicate (d spacing=53 and 18 A, respectively), which became accessible for BSA protein embedding. Subsequent BSA substitution allowed the embedding of the protein into the layered clay galleries in an uncompressed conformation. The stepwise process of embedding large molecules into the silicate gallery provides a new method for synthesizing biomaterial/clay hybrids potentially useful in drug delivery or biomedical design. PMID- 17279687 TI - Adsorption of trypsin on hydrophilic and hydrophobic surfaces. AB - The adsorption of trypsin onto polystyrene and silica surfaces was investigated by reflectometry, spectroscopic methods, and atomic force microscopy (AFM). The affinity of trypsin for the hydrophobic polystyrene surface was higher than that for the hydrophilic silica surface, but steady-state adsorbed amounts were about the same at both surfaces. The conformational characteristics of trypsin immobilized on silica and polystyrene nanospheres were analyzed in situ by circular dichroism and fluorescence spectroscopy. Upon adsorption the trypsin molecules underwent structural changes at the secondary and tertiary level, although the nature of the structural alterations was different for silica and polystyrene surfaces. AFM imaging of trypsin adsorbed on silica showed clustering of enzyme molecules. Rinsing the silica surface resulted in 20% desorption of the originally adsorbed enzyme molecules. Adsorption of trypsin on the surface of polystyrene was almost irreversible with respect to dilution. After adsorption on silica the enzymatic activity of trypsin was 10 times lower, and adsorbed on polystyrene the activity was completely suppressed. The trypsin molecules that were desorbed from the sorbent surfaces by dilution with buffer regained full enzymatic activity. PMID- 17279688 TI - Nanoscale indentation of polymer and composite polymer-silica core-shell submicrometer particles by atomic force microscopy. AB - Atomic force microscopy was employed to probe the mechanical properties of surface-charged polymethylmethacrylate (PMMA)-based terpolymer and composite terpolymer core-silica shell particles in air and water media. The composite particles were achieved with two different approaches: using a silane coupling agent (composite A) or attractive electrostatic interactions (composite B) between the core and the shell. Young's moduli (E) of 4.3+/-0.7, 11.1+/-1.7, and 8.4+/-1.7 GPa were measured in air for the PMMA-based terpolymer, composite A, and composite B, respectively. In water, E decreases to 1.6+/-0.2 GPa for the terpolymer; it shows a slight decrease to 8.0+/-1.2 GPa for composite A, while it decreases to 2.9+/-0.6 GPa for composite B. This trend is explained by considering a 50% swelling of the polymer in water confirmed by dynamic light scattering. Close agreement is found between the absolute values of elastic moduli determined by nanoindentation and known values for the corresponding bulk materials. The thickness of the silica coating affects the mechanical properties of composite A. In the case of composite B, because the silica shell consists of separate particles free to move in the longitudinal direction that do not individually deform when the entire composite deforms, the elastic properties of the composites are determined exclusively by the properties of the polymer core. These results provide a basis for tailoring the mechanical properties of polymer and composite particles in air and in solution, essential in the design of next generation abrasive schemes for several technological applications. PMID- 17279689 TI - Influence of the extent of hybridization on the hydrodynamic radius of DNA functionalized gold nanoparticles. AB - A combination of fluorescence spectroscopy and dynamic laser light scattering is used to investigate the relationship between the extent of hybridization on the surface of DNA-functionalized gold nanoparticles and the hydrodynamic radius (Rh) of the nanoparticle. The hydrodynamic radius of the DNA-Au conjugate increases measurably only after approximately 5-10 DNA hybridization events and saturates at its maximum value well before the surface is fully loaded. PMID- 17279690 TI - Examination of interactions of oppositely charged proteins in gels. AB - Understanding the interactions of proteins with one another serves as an important step for developing faster protein separation methods. To examine protein-protein interactions of oppositely charged proteins, fluorescently labeled albumin and poly-l-lysine were subjected to electrophoresis in agarose gels, in which the cationic albumin and the anionic poly-L-lysine were allowed to migrate toward each other and interact. Fluorescence microscopy was used to image fluorescently tagged proteins in the gel. The secondary structure of the proteins in solution was studied using conventional FTIR spectroscopy. Results showed that sharp interfaces were formed where FITC tagged albumin met poly-L-lysine and that the interfaces did not migrate after they had been formed. The position of the interface in the gel was found to be linearly dependent upon the relative concentration of the proteins. The formation of the interface also depended upon the fluorescent tag attached to the protein. The size of the aggregates at the interface, the fluorescence intensity modifications, and the mobility of the interface for different pore sizes of the gel were investigated. It was observed that the interface was made up of aggregates of about 1 microm in size. Using dynamic light scattering, it was observed that the size of the aggregates that formed due to interactions of oppositely charged proteins depended upon the fluorescent tags attached to the proteins. The addition of small amounts of poly L-lysine to solutions containing FITC albumin decreased the zeta potential drastically. For this, we propose a model suggesting that adding small amounts of poly-L-lysine to solutions containing FITC -albumin favors the formation of macromolecular complexes having FITC albumin molecules on its surface. Although oppositely charged FITC tagged poly-L-lysine and FITC tagged albumin influence each other's migration velocities by forming aggregates, there were no observable secondary structural modifications when the proteins were mixed in solution. PMID- 17279691 TI - Field effect transistors with organic semiconductor layers assembled from aqueous colloidal nanocomposites. AB - We demonstrate field effect transistors based on organic semiconductor molecules dispersed in a self-organized polystyrene (PS) latex bead matrix. An aqueous colloidal composite made of PS and tetrahexylsexithiophene (H4T6) is deposited with a micropipet into the channel of a bottom-contact field effect transistor. The beads self-organize into a network whose characteristic distances are governed by their packing. The semiconductor molecules crystallize in the interstitial voids, leading to the growth of large interconnected domains. Depending on the bead size and the ratio between H4T6 and PS, the fraction of the different phases in the polymorph can be controlled. In the transistors where the H4T6 metastable "red phase" is the largest, the device response and the charge mobility are comparable to those of sexithienyl thin films grown by high-vacuum sublimation. PMID- 17279692 TI - Thermodynamic and spectroscopic studies on the nickel arachidate-RNA polymerase Langmuir-Blodgett monolayer. AB - The Langmuir-Blodgett (LB) monolayers offer a unique system to study molecular interaction at the air-water interface with reduced dimensionality. In order to develop this further to follow macromolecular interactions at equilibrium, we first characterized the Ni (II)-arachidate (NiA) monolayer at varying conditions. Subsequently, the interaction between NiA and histidine-tagged RNA polymerase (HisRNAP) were also studied. LB films of arachidic acid-NiA and NiA-RNAP with different mole fractions were fabricated systematically. Surface pressure versus area per molecule (P-A) isotherms were registered, and the excess Gibbs energy of mixing was calculated. The LB films were then deposited on solid supports for Fourier transform infrared (FTIR) spectroscopic measurements. The FTIR spectra revealed the change in the amount of incorporated Ni (II) ions into the arachidic acid monolayer with the change in pH and the increasing mole fraction of RNAP in the NiA monolayer with its increasing concentration in the subphase. The system developed here seems to be robust and can be utilized to follow macromolecular interactions. PMID- 17279693 TI - Adsorption behavior of glucose oxidase on a dipalmitoylphosphatic acid monolayer and the characteristics of the mixed monolayer at air/liquid interfaces. AB - A dipalmitoylphosphatic acid (DPPA) monolayer at the air/liquid interface is used as a binding layer to incorporate glucose oxidase (GOx) from the subphase. The effects of the adsorption time of GOx on the behavior of the mixed DPPA/GOx monolayer and the relevant structure of the mixed LB film were studied using the characteristics of the pressure-area (pi-A) isotherm, Brewster angle microscopy (BAM), and atomic force microscopy (AFM). The experimental results show that two equilibrium states of GOx adsorption exist in the presence of a DPPA monolayer. The first equilibrium stage occurs at tens of minutes after spreading of DPPA, and a surface pressure of ca. 7.5 mN/m is obtained. The second equilibrium stage approaches slowly, and a higher equilibrium surface pressure (ca. 16 mN/m) was obtained at ca. 8 h after the first stage. The BAM and AFM images show that, after the second equilibrium stage is reached, a more condensed phase and rough morphology are obtained on the mixed DPPA/GOx monolayer, indicating a higher amount of GOx incorporated into the mixed film. For the first equilibrium stage of GOx adsorption, DPPA molecules can still pack regularly and closely under compression, suggesting that GOx molecules are mainly located beneath the DPPA monolayer at the compressed state. A more uniform phase was detected on a film prepared after the first equilibrium stage was reached. The present result indicates that distinct structures and properties of mixed DPPA/GOx films can be prepared from the various stages of GOx adsorption. PMID- 17279694 TI - Hybrid protein-lipid patterns from aluminum templates. AB - An aqueous aluminum liftoff process suitable for fabrication of hybrid patterns of protein and supported lipid membrane on silica surfaces is described. Patterned aluminum thin films, which can be produced by conventional optical or electron beam lithography, are employed as sacrificial protecting layers to define the geometry of the protein-lipid patterns. The aluminum is lifted off in a mildly basic aqueous solution, which preserves the integrity of bound protein layers. The newly exposed substrate can then be filled with supported membrane by exposure to an aqueous vesicle suspension. The final substrate consists of patterned protein and lipid membranes with spatial resolution determined by aluminum patterns, down to 200 nm line widths in this case. Inorganic surfaces were characterized by atomic force microscopy and X-ray photoelectron spectroscopy while supported bilayers and protein patterns were characterized by epifluorescence microscopy. PMID- 17279695 TI - Stabilization of peptide fibrils by hydrophobic interaction. AB - Hydrophobic interactions play an important role in assembly processes in aqueous environments. In case of peptide amphiphiles, hydrophobicity is combined with hydrogen bonding to yield well-defined peptide-based aggregates. Here, we report a systematic study after the role of hydrophobic interactions on both stabilization and morphology of a peptide fibrillar assembly. For this purpose, alkyl tails were connected to a known beta-sheet forming peptide with the sequence KTVIIE. The introduction of n-alkyl groups induced thermal stability to the assemblies without affecting the morphology of the peptide aggregates. PMID- 17279696 TI - Microcalorimetric study of protein adsorption onto calcium hydroxyapatites. AB - To clarify the adsorption mechanism of proteins onto calcium hydroxyapatite (Hap), the present study measured adsorption (DeltaHads) and desorption (DeltaHdes) enthalpies of bovine serum albumin (BSA; isoelectric point (iep) 4.7, molecular mass (Ms) 67,200 Da, acidic protein), myoglobin (MGB; iep=7.0, Ms=17,800 Da, neutral protein), and lysozyme (LSZ; iep=11.1, Ms=14,600 Da, basic protein) onto Hap by a flow microcalorimeter (FMC). Five kinds of large platelike particles of CaHPO4.2H2O (DCPD) after hydrolyzing at room temperature with different concentrations of NaOH aqueous solution ([NaOH]) for 1 h were used. DCPD converted completely to Hap after treatment at [NaOH]>or=2%, and the crystallinity of Hap was increased with an increase in [NaOH] up to 10%. The amounts of protein adsorbed (Deltanads) and desorbed (Deltandes) were measured simultaneously by monitoring the protein concentration downstream from the FMC with a UV detector. The Deltanads values were also measured statically by a batch method in each system. The Deltanads values measured by the FMC and static measurements fairly agreed with each other. Results revealed that DeltaHBSAads was decreased with an increase in [NaOH]; in other words, DeltaHBSAads was decreased with the improvement of Hap's crystallinity, suggesting that the BSA adsorption readily proceeded onto Hap. This fact indicated a high affinity of Hap to protein. This affinity was further recognized by DeltaHBSAdes because its positive value was increased by increasing [NaOH]. These opposite tendencies in DeltaHBSAads and DeltaHBSAdes revealed that Hap possessed a high adsorption affinity to BSA (i.e., enthalpy facilitated protein adsorption but hindered its desorption). The fraction of BSA desorption was also decreased with an increase in [NaOH], confirming the high affinity of Hap to protein. Similar results were observed on the LSZ system, though the enthalpy values were smaller than those of BSA. In the case of neutral MGB, DeltaHBSAads also exhibited results similar to those of the BSA and LSZ systems. However, due to its weak adsorption by the van der Waals force, DeltaHBSAdes was small and almost zero at [NaOH]>or=2%. Hence, the fraction of MGB desorption was less dependent on [NaOH]. PMID- 17279697 TI - Olive oil microemulsions: enzymatic activities and structural characteristics. AB - Microemulsions composed of olive oil, either extravirgin (EVOO) or refined (ROO), as the continuous oil phase, water as the dispersed phase, and a mixture of lecithin-propanol as the emulsifier were prepared and investigated as potential biocompatible media for biotransformations. The area of the microemulsion zone increased considerably by increasing the lecithin to propanol weight ratio in both EVOO- and ROO-based systems. However, the nature of the oil used does not seem to affect the ability of the system to incorporate water. The catalytic activities of two oxidizing enzymes that have been detected in virgin olive oil, namely, tyrosinase and peroxidase, and the activity of a proteolytic enzyme such as trypsin were studied in olive oil microemulsions. In all cases a reduced catalytic activity was observed when ROO was considered as the continuous oil phase. The interfacial properties of lecithin layers were studied by electron paramagnetic resonance spectroscopy employing the nitroxide spin probe 5 doxylstearic acid. By varying the weight ratio of lecithin to propanol and the water content of the microemulsions, the mobility of the probe and the rigidity of the interface were altered. Droplet sizes were measured by dynamic light scattering. At higher water content of the system the size of the droplets was increased. When EVOO was considered as the oil phase, smaller aqueous droplets were formed. Lecithin-based olive oil microemulsions were also characterized with regard to the phenomenon of electrical percolation. At a water content above 3% (w/w) and a lecithin/propanol weight ratio of 2, a sharp increase in conductivity was observed, indicating a structural transition in the bicontinuous form. PMID- 17279698 TI - Adsorption of calf thymus DNA on Au(110) studied by reflection anisotropy spectroscopy. AB - Reflection anisotropy spectroscopy (RAS) was used to investigate the adsorption of single-stranded (ss-) and double-stranded (ds-) calf thymus DNA on Au(110) in an electrochemical cell. Both types of DNA form ordered structures for electrode potentials in the range from +0.6 to -0.4 V. Both types of DNA desorb at -0.6 V and may start desorbing at lower negative potentials. When adsorbed at +0.6 V, both forms give rise to a similar RAS signal and adsorb through the phosphate groups. As the potential is reduced, the RAS intensity observed from ss-DNA increases to roughly twice that observed from ds-DNA, a result that is interpreted as due to a change in the adsorption of the ss-DNA from sites involving the phosphate groups to sites involving the bases. PMID- 17279699 TI - Local and average diffusion of nanosolutes in agarose gel: the effect of the gel/solution interface structure. AB - Fluorescence correlation spectroscopy (FCS) has been used to study the diffusion of nanometric solutes in agarose gel, at microscopic and macroscopic scales. Agarose gel was prepared and put in contact with aqueous solution. Several factors were studied: (i) the role of gel relaxation after its preparation, (ii) the specific structure of the interfacial zone and its role on the local diffusion coefficient of solutes, and (iii) the comparison between the local diffusion coefficient and the average diffusion coefficient in the gel. Fluorescent dyes and labeled biomolecules were used to cover a size range of solutes of 1.5 to 15 nm. Their transport through the interface from the solution toward the gel was modeled by the first Fick's law based on either average diffusion coefficients or the knowledge of local diffusion coefficients in the system. Experimental results have shown that, at the liquid/gel interface, a gel layer with a thickness of 120 microm is formed with characteristics significantly different from the bulk gel. In particular, in this layer, the porosity of agarose fiber network is significantly lower than in the bulk gel. The diffusion coefficient of solutes in this layer is consequently decreased for steric reasons. Modeling of solute transport shows that, in the bulk gel, macroscopic diffusion satisfactorily follows the classical Fick's diffusion laws. For the tested solutes, the local diffusion coefficients in the bulk gel, measured at microscopic scale by FCS, were equal, within experimental errors, to the average diffusion coefficients applicable at macroscopic scales (>or=mm). This confirms that anomalous diffusion applies only to solutes with sizes close to the gel pore size and at short time (0.2 M. (iv) The Rh (78 nm) of the soluble complex at Cs from 0.3 to 0.5 M is larger than that at Cs<0.02 M, suggesting dissociation of the KPVS ions. (v) Complexation between KPVS and PDDA as mentioned in (ii) is facilitated in the presence of 0.01 M KCl. PMID- 17279701 TI - Influence of a reduced mobility layer on the structural relaxation dynamics of aluminum capped ultrathin films of poly(ethylene terephthalate). AB - The structural dynamics of ultrathin polymer films of poly(ethylene terephthalate) capped between aluminum electrodes have been investigated by dielectric relaxation spectroscopy. A deviation from bulk behavior, appearing as an increase of the relaxation time at a fixed temperature, is observed for films of thickness below 35 nm. The slowing down acts as a constant shift factor independent from the temperature, and the fragility is constant. The interfacial energy between aluminum and poly(ethylene terephthalate) is calculated to be 3 mJ/m2, confirming a strong interaction between polymer and substrate, which leads to the presence of a layer characterized by a reduced mobility at their interfaces. We proposed a mathematical schematization of a multylayer model that allowed qualitative reproduction of the observed thickness dependences of the static and dynamic properties. In terms of such a model, the upper limit for the thickness of the reduced mobility layer was estimated as 20 nm. The conditions to extend the proposed model to different observables are finally suggested. PMID- 17279702 TI - Synthesis, characterization, and surface properties of iron-doped boehmite nanofibers. AB - Iron-doped boehmite nanofibers with varying iron contents have been prepared at low temperatures using hydrothermal treatment in the presence of poly(ethylene oxide) surfactant. The resulting nanofibers were characterized by transmission electron microscopy (TEM), X-ray diffraction, energy-dispersive X-ray analysis, and N2 adsorption. TEM images showed that the resulting nanostructures are predominantly nanofibers when the doped iron content is less than 5% (mol/mol); in contrast, nanosheets were formed when iron doping was above 4%. Nanotubes instead of nanofibers and iron-rich particles were observed in samples with 20% added iron. A detailed characterization and discussion on the iron-doped nanofibers is presented. PMID- 17279704 TI - Monolayer-protected gold nanoparticles by the self-assembly of micellar poly(ethylene oxide)-b-poly(epsilon-caprolactone) block copolymer. AB - A study is presented of the preparation of gold nanoparticles incorporated into biodegradable micelles. Poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b PCL) copolymer was synthesized by ring-opening polymerization, and the hydroxyl end group of the PCL block was modified with thioctic acid using dicyclohexyl carbodiimide as the coupling reagent. The PEO-b-PCL-thioctate ester (TE) thus obtained was used in a later step to form monolayer protected gold nanoparticles via the thioctate spacer. Gold nanoparticles stabilized with the PEO-b-PCL block (named Au/Block (x/y), where x/y is the mole feed ratio between HAuCl4 and PEO-b PCL-TE) were prepared and analyzed. Au/Block (1/1), Au/Block (2/1), and Au/Block (3/1) nanoparticles were found to form stable dispersions in the organic solvents commonly used to dissolve the unlabeled block copolymer. The average diameter of the nanoparticles was determined by transmission electron microscopy (TEM) and found to be 6+/-2 nm. Au/Block (4/1) nanoparticle dispersions in organic solvents, on the other hand, were not stable and produced large gold clusters (50 100 nm). Cluster formation was attributed to the low grafting density of the block copolymer, which facilitates agglomeration. For Au/Block (12/1), along the same trend, only an insoluble product was isolated. Micelles in water were prepared by the slow addition of the dilute Au/Block solution in dimethylformamide into a large excess of water with vigorous stirring. Au/Block (1/1) and Au/Block (2/1) formed nanosized structures of 5-7 nm. TEM images of stained Au/Block (1/1) micelles, made in water, clearly showed the formation of core-shell structures. Au/Block (3/1) micelles, on the other hand, were not stable and large agglomerates a few microns in size were observed. The study focuses on the synthesis, characterization, and aggregation behavior of gold loaded PEO-b-PCL block copolymer micelles, a potential system for drug delivery in conjunction with tissue and subcellular localization studies. PMID- 17279703 TI - Block-copolymer micro-emulsion with solvent-induced segregation. AB - Reverse micelle formation of the poly(ethylene oxide)/poly(propylene oxide) block copolymer (EO)13(PO)30(EO)13 (L64) in p-xylene was investigated as a function of water content and copolymer content, using small-angle neutron scattering (SANS). PEO/PPO block-copolymers are generally soluble in xylene but without forming aggregates. However, the effective block segregation increases dramatically upon addition of small amounts of water, and micelles form. The SANS data were analyzed using an absolute scale model fitting approach. This way, a detailed quantitative description of the system in terms of unimer concentration, micelle structure, and aggregation number as well as particle-particle interactions can be obtained. This approach throws light on very atypical features of the system as compared to standard amphiphilic systems. Data from samples measured along water-swelling lines with fixed EO/p-xylene-d10 molar ratios show that reverse micelles are formed at the water/EO molar ratio, W0 congruent with 0.2, independent of copolymer concentration. The majority of the block-copolymers are on a free monomer state (unimer state) at this W0. Increasing W0 above 0.2 only has a small effect on the micelle size. However, it does induce a strong increase of the total number of micelles and induce a corresponding decrease of the unimer concentration. On the other hand, increasing the overall copolymer concentration at fixed W0 gives rise to a significant decrease of the micelle size in terms of the micellar aggregation number. This observed behavior is totally different from what is normally observed for binary surfactant-solvent systems and droplet micro emulsion systems, respectively. We believe that the atypical behavior is a result of the unusually weak segregation in the system, and we are not aware of previous discussions of the phenomenon for reverse micellar systems. PMID- 17279705 TI - Synthesis, characterization, and immobilization of Prussian blue-modified Au nanoparticles: application to electrocatalytic reduction of H2O2. AB - Au nanoparticles modified with electroactive Prussian blue (PB) were for the first time synthesized by a simple chemical method. Transmission electronic microscopy showed that the average size of the Prussian blue shell/Au core hybrid composite (PB@Au) was about 50 nm, and Fourier transform IR, UV-vis spectra, and cyclic voltammetry confirmed the existence of PB on the surface of Au nanoparticles. Using the LbL technique, multilayer thin films of PB@Au nanoparticles were prepared by the alternate adsorption of oppositely charged linear polyelectrolyte poly(allylamine hydrochloride) (PAH) onto ITO glass for the construction of a hydrogen peroxide sensor. The novel multilayer films were characterized by SEM, cyclic voltammetry, and UV-visible absorption spectroscopy. The {PAH/PB@Au}n multilayer-modified electrode showed a well-defined pair of redox peaks and dramatic catalytic activity toward the reduction of hydrogen peroxide. PMID- 17279706 TI - Design of ordered bimodal mesoporous silica materials by using a mixed fluorinated-hydrogenated surfactant-based system. AB - Mesoporous silica materials have been prepared using aqueous solutions of hydrogenated-fluorinated surfactant mixtures. The phase behavior of the C18H35(OC2H4)10-C6F15C2H4(OC2H4)11OH [RH18(EO)10-RF6(EO)11] mixture in aqueous solution was first established at the temperature at which the silica source is added, i.e., 20 or 40 degrees C. We have delimited the different phase domains. Concerning the mesostructured silica, whatever the temperature at which the silica source is added, mesoporous material with a hexagonal array of their channel is formed via a cooperative templating mechanism (CTM), if the content of RF6(EO)11 in the surfactant mixture is lower than 50%. Moreover, when the silica source is added at 40 degrees C, the recovered materials exhibit a bimodal pore size distribution. The appearance of this bimodality has been related to the coexistence of hydrogenated micelles with fluorinated wormlike micelles. By contrast, the bimodality is not observed when the silica source is added at 20 degrees C. PMID- 17279707 TI - Nitrogen distribution at 77.7 K in mesoporous Gelsil 50 generated via evolutionary minimization with statistical descriptors derived from adsorption and in situ SANS. AB - Digitized periodic material models of size 100(3) nm3 of mesoporous xerogel Gelsil 50 are reconstructed by use of an evolutionary minimization technique, with two-point probability S2(r) and volume-based pore size distribution Psi(D) as a hybrid target function. S2(r) and Psi(D) are derived from small-angle neutron scattering (SANS) and adsorption data, respectively. The nitrogen distribution in Gelsil 50 is characterized in the multilayer adsorption and capillary-condensation regimes by S2(r) and statistical parameters obtained from in situ SANS data. The fraction of liquid-free pore space varphi is calculated from nitrogen adsorption data, and the distribution Psicorr(D) of the diameter of the liquid-free pore space at certain relative pressures is derived from Psi(D). The evolutionary algorithm is also used to generate the spatial nitrogen distribution by means of the descriptors varphi, S2(r), and Psicorr(D). The morphological parameters obtained from the reconstructs are compared to the respective SANS results. PMID- 17279708 TI - Functionalization of monodisperse magnetic nanoparticles. AB - We report a new strategy for the preparation of monodisperse, water-soluble magnetic nanoparticles. Oleic acid-stabilized magnetic nanocrystals were prepared by the organic synthesis route proposed by Sun et al. (J. Am. Chem. Soc. 2004, 126, 273.), with size control obtained via seeded-mediated growth. The oleic groups initially present on the nanoparticle surfaces were replaced via ligand exchange reactions with various capping agents bearing reactive hydroxyl moieties. These hydroxyl groups were (i) exploited to initiate ring opening polymerization (ROP) of polylactic acid from the nanoparticle surfaces and (ii) esterified by acylation to permit the addition of alkyl halide moieties to transform the nanoparticle surfaces into macroinitiators for atom transfer radical polymerization (ATRP). By appropriate selection of the ligand properties, the nanoparticle surfaces can be polymerized in various solvents, providing an opportunity for the growth of a wide variety of water-soluble polymers and polylectrolyte brushes (both cationic and anionic) from the nanoparticle surfaces. The nanoparticles were characterized by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), electron microscopy, and light scattering. Light scattering measurements indicate that the nanoparticles are mostly present as individual nonclustered units in water. With pH-responsive polymers grown on the nanoparticle surfaces, reversible aggregation of nanoparticles could be induced by suitable swings in the pH between the stable and unstable regions. PMID- 17279709 TI - Superhydrophobic bionic surfaces with hierarchical microsphere/SWCNT composite arrays. AB - Superhydrophobic bionic surfaces with hierarchical micro/nano structures were synthesized by decorating single-walled or multiwalled carbon nanotubes (CNTs) on monolayer polystyrene colloidal crystals using a wet chemical self-assembly technique and subsequent surface treatment with a low surface-energy material of fluoroalkylsilane. The bionic surfaces are based on the regularly ordered colloidal crystals, and thus the surfaces have a uniform superhydrophobic property on the whole surface. Moreover, the wettability of the bionic surface can be well controlled by changing the distribution density of CNTs or the size of polystyrene microspheres. The morphologies of the synthesized bionic surfaces bear much resemblance to natural lotus leaves, and the wettability exhibited remarkable superhydrophobicity with a water contact angle of about 165 degrees and a sliding angle of 5 degrees. PMID- 17279710 TI - Highly fluorescent rhodamine B nanoparticles entrapped in hybrid glasses. AB - Rhodamine B (RB) nanoparticles entrapped in hybrid glasses show enhanced fluorescent emission (approximately 220-fold larger than that of single RB molecules) thanks to the configuration control of the self-assembled aggregates that form the supramolecular architecture of the nanoparticles. The fluorescence performance reported in this work is around 1 order of magnitude larger than that recently reported for fluorescent Nile Red nanoparticles. The fluorescence enhancement results from the use of a highly efficient fluorescent dye such RB and the formation of larger nanoparticles. Note that the later implies the presence of a large number of emitting centers involved in the fluorescence emission. PMID- 17279711 TI - Spontaneous pattern formation by dip coating of colloidal suspensions on homogeneous surfaces. AB - We study the slow withdrawal of a partially wet vertical plate at velocity U from a suspension of well-wet particles. Periodic horizontal striped assemblies form spontaneously at the three-phase contact line on energetically uniform surfaces. Stripe width and spacing depend on the withdrawal velocity U relative to a transition velocity Ut. Thick stripes separated by large spaces form for UUt, thin stripes separated by small spaces form. The stripe spacing is reduced by an order of magnitude and varies weakly with U until a maximum velocity is reached at which the stripes fail to form. A partially wet surface can entrain a meniscus. For UUt, we infer that a film of thickness h is entrained above the meniscus. When h is smaller than the particle diameter D, particles aggregate where the entrained film thickens to match up to the wetting meniscus. When an entrained particle becomes exposed to air by evaporation, it becomes the new pinning site from which the next film is entrained. The film thickness h increases with U; at some velocity, h becomes comparable to D. Particles flow into the film and deposit there in a disordered manner. A diagram summarizing particle deposition is developed as a function of D, U, and h. PMID- 17279712 TI - Thin film fabrication of PMMA/MEH-PPV immiscible blends by corona discharge coating and its application to polymer light emitting diodes. AB - We introduce a new and facile process, corona discharge coating (CDC), to fabricate thin polymer films of the immiscible poly[2-methoxy-5-(2' ethylhexyloxy)-p-phenylenevinylene] (MEH-PPV) and poly(methyl methacrylate) (PMMA) blends. The method is based on utilizing directional electric flow, known as electric wind, of the charged unipolar particles generated by corona discharge between a metallic needle and a bottom plate under high electric field (5-10 kV/cm). The electric flow rapidly spreads out the polymer solution on the bottom plate and subsequently forms a smooth and flat thin film over a large area within a few seconds. The method is found to be effective for fabricating uniform thin polymer films with areas larger than approximately 30 mm2. The thin films obtained by CDC exhibit unique microstructures where well-defined spherical and cylindrical domains of approximately 50 nm in diameter coexist. These nanosized domains are found to be much smaller than those in films made by conventional spin coating, which suggests that CDC is beneficial for fabricating phase separated thin film structures with significantly increased interfacial areas. The effects of the applied voltage, tip-to-plate distance, and substrates on the film formation as well as the resulting microstructure are investigated. Furthermore, the light emitting performance of a device prepared by CDC is compared with one made by spin coating. PMID- 17279713 TI - Cooperative binding of nonionic surfactant to hydrophobically modified polyanions as studied by frontal analysis continuous capillary electrophoresis. AB - The binding of a nonionic surfactant, Triton X-100 (TX), to amphiphilic copolymers of sodium 2-(acrylamido)-2-methylpropanesulfonate and N dodecylmethacrylamide (C12) (p(A/C12(x)), where x denotes the mol % content of C12) was investigated by frontal analysis continuous capillary electrophoresis (FACCE) combined with dynamic light scattering focusing on the effect of the hydrophobe content on the binding in a wide range of x (5-60 mol %). From binding isotherms obtained from FACCE data, the binding was found to be cooperative in the whole range of x. Furthermore, a significant change in the binding behavior, i.e., cooperativity, was found to occur in a relatively narrow range of x (38-50 mol %), which is attributable to a change in the self-association behavior of p(A/C12(x)) in this x range. PMID- 17279714 TI - Multicomponent nanoparticles via self-assembly with cross-linked block copolymer surfactants. AB - We describe a simple and versatile protocol to prepare water-soluble multifunctional nanostructures by encapsulation of different nanoparticles in shell cross-linked, block copolymer micelles. This method permits simultaneous incorporation of different nanoparticle properties within a nanoscale micellar container. We have demonstrated the co-encapsulation of magnetic (gamma-Fe2O3 and Fe3O4), semiconductor (CdSe/ZnS), and metal (Au) nanoparticles in different combinations to form multicomponent micelles that retain the precursor particles' distinct properties. Because these multifunctional hybrid nanostructures spontaneously assemble from solution by simultaneous desolvation of nanoparticles and amphiphilic block copolymer components, we anticipate that this can be used as a general protocol for preparing multifunctional nanostructures without explicit multimaterial synthesis or surface functionalization of nanoparticles. PMID- 17279715 TI - Micromechanical cantilever technique: a tool for investigating the swelling of polymer brushes. AB - Polymer brush coatings are well-known for their ability to tailor surface properties in a wide range of applications from colloid stabilization to medicine. In most cases, the brushes are used in solution. Consequently, efforts were expended to experimentally investigate or theoretically predict the swelling behavior of the brushes in solvents of different qualities. Here, we show that the micromechanical cantilever (MC) sensor technique is a tool to perform time resolved physicochemical investigations of thin layers such as polymer brushes. Complementary to scattering techniques, which measure the thickness, the MC sensor technique provides information about changes in the internal pressure of the brushes during a swelling and deswelling process. We show that the kinetics of both swelling and deswelling are dependent on solvent quality. Comparing the measured data with its thickness evolution, which was calculated based on the Flory-Huggins theory, we found that only the first 10% of the thickness increase of the polymer brush results in a significant pressure increase inside the polymer brush layer. PMID- 17279716 TI - Temperature-induced transport of thermosensitive hairy hybrid nanoparticles between aqueous and organic phases. AB - This paper reports on the temperature-induced transport of thermosensitive polymer brush-grafted silica nanoparticles between aqueous and organic phases. Poly(methoxytri(ethylene glycol) methacrylate), a thermosensitive water-soluble polymer with a cloud point of approximately 48 degrees C in H2O, was grown on silica nanoparticles by surface-initiated atom transfer radical polymerization in the presence of a free initiator. These hairy particles were found to quantitatively transfer from aqueous to ethyl acetate phases upon heating at 60 degrees C under the stirring condition. Cooling in an ice/water bath caused the particles to move from ethyl acetate to the aqueous layer. The concentrations of the particles in the original phases during the transport processes were monitored by UV-vis spectrometry. When mutually saturated water and ethyl acetate were used, the transport rates of the particles between the two phases were enhanced. The faster transport was attributed to the solvent phase separation, which produced liquid droplets, dramatically increased the interfacial area, and hence facilitated the transport of the particles. The reversible transfer of the particles between the aqueous and ethyl acetate phases upon heating at 60 degrees C and cooling in an ice/water bath can be repeated consecutively at least 10 times. The hairy particles can also be quantitatively transported from 1-butanol and toluene to H2O by stirring in an ice/water bath. However, only 60% of the particles transferred from water to 1-butanol and no particles to toluene upon heating at 60 degrees C. The reasons are discussed. PMID- 17279717 TI - Thiol-frozen shape evolution of triangular silver nanoplates. AB - The structural and optical stability of nanoparticles directly influences their applications. The shape evolution of silver nanoplates synthesized in the presence of bis(2-ethylhexyl) sulfosuccinate (AOT) could be effectively frozen using thiols in aqueous solution. These thiols (e.g., 1-hexanethiol, 1 octanethiol, 1-dodecanethiol, and 1-hexadecanethiol) exhibit stronger surface affinity on the silver crystalline surfaces. This is evidenced from both the unchanged shape/size of nanoplates and their unshifted plasmon resonances in optical absorption. To quantitatively explain the thiol-frozen shape evolution mechanism of silver nanoplates at molecular scale, molecular dynamics simulation was performed. The results show that these thiols exhibit larger interaction energies than AOT molecules on the silver atomic surfaces and hence freeze the shape evolution of silver nanoparticles. This thiol-frozen strategy would not only be useful for stabilizing nanoparticles but would also allow the introduction of a wide range of surface chemical functionalities to the nanoparticles for potential applications in nanosensors. PMID- 17279718 TI - Biocompatible polymer vesicles from biamphiphilic triblock copolymers and their interaction with bovine serum albumin. AB - The self-assembly of the biamphiphilic triblock copolymer poly(ethylene oxide)-b poly(caprolactone)-b-poly(acrylic acid) into polymer vesicles is studied. The vesicles provide both biocompatibility and biodegradability. Moreover, the biamphiphilic nature of the triblock copolymer provides different surface properties in the interior and in the outer interface of the vesicles. Preparation of the aggregates by direct dissolution of the copolymer in a solution of albumin does not alter the morphology of the aggregates, and thus, they have the potential to immobilize protein molecules. Since a part of the protein is encapsulated in the interior of the vesicles, they can be used as nanocontainers. A further fraction of the protein is bound to the outer interface, which is primarily composed of the poly(acrylic acid) tails. Immobilization of protein on the outer interface can stabilize the colloidal particles and also provide them with a biofunctional component. PMID- 17279719 TI - Responsive thin hydrogel layers from photo-cross-linkable poly(N isopropylacrylamide) terpolymers. AB - The structural features and swelling properties of responsive hydrogel films based on poly(N-isopropylacrylamide) copolymers with a photo-cross-linkable benzophenone unit were investigated by surface plasmon resonance, optical waveguide mode spectroscopy, and atomic force microscopy. The temperature dependent swelling behavior was studied with respect to the chemical composition of the hydrogel polymers containing either sodium methacrylate or methacrylic acid moieties. In the sodium methacrylate system, a refractive index gradient was found that was not present in the free acid gel. This refractive index gradient, perpendicular to the swollen hydrogel film surface, could be analyzed in detail by application of the reversed Wentzel-Kramers-Brillouin (WKB) approximation to the optical data. This novel approach to analyzing thin-film gradients with the WKB method presents a powerful tool for the characterization of inhomogeneous hydrogels, which would otherwise be very difficult to capture experimentally. In AFM images of the hydrogel layers, a macroscopic pore structure was observed that depended on the polymer composition as well as on the swelling history. This pore structure apparently prevents the often-observed skin barrier effect and leads to a quickly responding hydrogel. PMID- 17279720 TI - Voltammetric measurements at the surface of cotton: absorption and catalase reactivity of a dinuclear manganese complex. AB - Voltammetric measurements at the surface of cotton fabric were conducted after impregnating the surface of the textile with graphite flakes. The resulting conducting surface contact was connected to a conventional basal plane pyrolytic graphite substrate electrode and employed both in stagnant solution and in rotating disc voltammetry mode. Diffusion through the immobilized cotton sample (inter-fiber) is probed with the aqueous Fe(CN)6(4-/3-) redox system. With a small amount of platinum immobilized at the cotton surface, catalase reactivity toward hydrogen peroxide was observed and used to further quantify the diffusion (intra- and inter-fiber) into the reactive zone at the graphite-cotton interface. A well-known catalase model system, the dinuclear manganese metal complex [Mn(IV)2(micro-O)3L2](PF6)2 (with L=1,4,7-trimethyl-1,4,7-triazacyclononane), is investigated in aqueous 0.1 M carbonate buffer at pH 9.8 in contact with cotton fabric. Absorption of the metal complex is monitored and quantified by voltammetric methods. A Langmurian binding constant of approximately K=2x103 M-1 was determined. Voltammetric measurements of the adsorbed metal complex reveal strong absorption and chemically irreversible reduction characteristics similar to those observed in solution. In the presence of hydrogen peroxide, catalyst coverage dependent anodic catalase activity was observed approximately following the rate law rate=k[catalyst]surface[H2O2]solution and with k=3x104 dm3 s-1 mol 1. The catalyst reactivity was modified by the presence of cotton. PMID- 17279721 TI - Fully ferrocenated hexanethiolate monolayer-protected gold clusters. AB - The synthesis and compositional analysis of four different gold clusters with protecting monolayers comprised solely of ferrocene hexanethiolate ligands is described. The gold nanoparticles have average core diameters of 1.4, 1.6, 2.0, and 2.2 nm with estimated average atom counts of 55, 140, 225, and 314 Au atoms and average monolayer coverages of 37, 39, 43, and 58 ferrocenated ligands, respectively. The data show unequivocally that the number of ferrocene hexanethiolate ligands bound to each core size is constrained by the steric requirements of the ferrocene head group; the ligand numbers are significantly smaller than those for hexanethiolate ligands bonded to analogous-sized Au cores. Voltammetry of dilute solutions of these nanoparticles shows a large ferrocene oxidation wave and, at more negative potentials, smaller one-electron waves for the quantized double-layer charging of the Au cores. Together, the ferrocenes and core of the ferrocenated Au314 nanoparticle deliver 60 electrons at the ferrocene oxidation potential, which amounts to a very large volume charge capacity, 7x10(9) C/m3, for an undiluted nanoparticle sample. PMID- 17279722 TI - Using three-phase flow of immiscible liquids to prevent coalescence of droplets in microfluidic channels: criteria to identify the third liquid and validation with protein crystallization. AB - This manuscript describes the effect of interfacial tensions on three-phase liquid-liquid-liquid flow in microfluidic channels and the use of this flow to prevent microfluidic plugs from coalescing. One problem in using microfluidic plugs as microreactors is the coalescence of adjacent plugs caused by the relative motion of plugs during flow. Here, coalescence of reagent plugs was eliminated by using plugs of a third immiscible liquid as spacers to separate adjacent reagent plugs. This work tested the requirements of interfacial tensions for plugs of a third liquid to be effective spacers. Two candidates satisfying the requirements were identified, and one of these liquids was used in the crystallization of protein human Tdp1 to demonstrate its compatibility with protein crystallization in plugs. This method for identifying immiscible liquids for use as a spacer will also be useful for applications involving manipulation of large arrays of droplets in microfluidic channels. PMID- 17279723 TI - Tethering of modified Reichardt's dye on SBA-15 mesoporous silica: the effect of the linker flexibility. AB - Solvatochromic Reichardt's dye has been covalently anchored to both aniline functionalized and propylamine-functionalized SBA-15 mesoporous silicas. The former offers a rigid linker to the surface; the latter offers a flexible one. The optical properties of immobilized dye in the presence of various vapors and gases were investigated by means of in situ diffuse reflectance UV-visible spectroscopy. The nature of the linker (rigid or flexible), used to covalently immobilize the dye, was found to play a significant role in determining the solvatochromic response of the chromophore to molecules. The use of the rigid linker, which reduces dye-support secondary interactions, represents a significant improvement in view of sensing applications, due to the stronger effects of the interaction with molecules from the gas or vapor phase on the visible absorption spectrum. This study provides a direct observation of the effect of linker flexibility on the behavior of anchored species. PMID- 17279725 TI - Comment on "Disposable receptor-based optical sensor for nitrate". PMID- 17279724 TI - Water-soluble polymer conjugates of ZnPP for photodynamic tumor therapy. AB - Zn-protoporphyrin (ZnPP) is a promising candidate for cancer therapy. It is known to inhibit heme-oxygenase-1 (HO-1), resulting in suppressed biliverdin/bilirubin production accompanying lowered antioxidative capacity. As a consequence, a significant suppression of tumor growth in vivo was reported. Recent findings also showed that ZnPP efficiently generated reactive singlet oxygen under illumination of visible light. In the present report, we describe the photosensitizing capabilities of water-soluble polymer conjugates of ZnPP as novel compounds for photodynamic therapy against solid tumors. The polymer conjugation made ZnPP water-soluble, thus possible for injection for its aqueous solution. The cellular uptake and photobiological activity of ZnPP derivatives have been tested using a human T-cell leukemia cell line in vitro and demonstrated most potent phototoxic effects of SMA-ZnPP followed by PEG-ZnPP under aerobic conditions. PMID- 17279726 TI - Exploiting small molecule binding to DNA for the detection of single-nucleotide mismatches and their base environment. AB - Naphthyridine-azaquinolone (Npt-Azq, described previously by Nakatani et al. ( Nakatani, K.; Hagihara, S.; Goto, Y.; Kobori, A.; Hagihara, M.; Hayashi, G.; Kyo, M.; Nomura, M.; Mishima, M.; Kojima, C. Nat. Chem. Biol. 2005, 1, 39-43.), was exploited to detect an adenine-adenine mismatch with a symmetrical G-C flanking sequence (5'-GAC-3'/5'-CAG-3') in a synthetic 20-mer DNA by electrochemical impedance spectroscopy. This innovative strategy enables us to obtain information about the presence of a specific mismatch in addition to sequence information. Npt-Azq binds the G-A region of the mismatch, which causes significant changes in the structure of the DNA, which in turn causes changes in the electrochemical properties of DNA/Npt-Azq films. For a 20-mer DNA containing an A-A mismatch, the electron-transfer resistance (RCT) of the system is significantly different in the presence of bound Npt-Azq, presumably due to the structural differences in the two films. Npt-Azq does not bind to matched DNA, and thus, the presence of Npt-Azq does not affect the electrochemical properties of such films. PMID- 17279727 TI - Atmospheric pressure covalent adduct chemical ionization tandem mass spectrometry for double bond localization in monoene- and diene-containing triacylglycerols. AB - We report a method to elucidate the structure of triacyl-glycerols (TAGs) containing monoene or diene fatty acyl groups by atmospheric pressure covalent adduct chemical ionization (APCACI) tandem mass spectrometry using acetonitrile as an adduct formation reagent. TAGs were synthesized with the structures ABB and BAB, where A is palmitate (C16:0) and B is an isomeric C18 monoene unsaturated at position 9, 11, or 13 or an isomeric diene unsaturated at positions 9 and 11, 10 and 12, or 9 and 12. In addition to the species at m/z 54 observed in previous CI studies of fatty acid methyl esters, we also found that ions at m/z 42, 81, and 95 undergo covalent reaction with TAGs containing double bonds to yield ions at m/z 40, 54, 81, and 95 units greater than that of the parent TAG: [M + 40]+, [M + 54]+, [M + 81]+, and [M + 95]+ ions. When collisionally dissociated, these ions fragment to produce two or three diagnostic ions that locate the double bonds in the TAG. In addition, ions [RCH=C=O + 40]+ and [RCH=C=O + 54]+ formed from collisional dissociation are of strong abundance in MS/MS spectra, and collisional activation of these ions produces two intense confirmatory diagnostic ions in the MS3 spectra. Fragment ions reflecting neutral loss of an sn-1-acyl group from [M + 40]+ and [M + 54]+ are more abundant than those reflecting neutral loss of an sn-2-acyl group, analogous to previous reports for protonated TAGs. The position of each acyl group on the glycerol backbone is thus determined by the relative abundances of these ions. Under the conditions in our instrument, the [M + 40]+ adduct is at the highest signal and also yields all information about the double bond position and TAG stereochemistry. With the exception of geometries about the double bonds, racemic TAG isomers containing two monoenes or dienes and a saturate can be fully characterized by APCACI-MS/MS/MS. PMID- 17279728 TI - Deconvolution microscopy for flow visualization in microchannels. AB - Quantitative visualization of microflows is often needed to evaluate the efficiency of fluid mixing, study flow properties, investigate unusual flow behavior, and verify computational fluid dynamic simulations. In this work, we explore the technique of coupling a conventional optical microscope with a computational deconvolution algorithm to produce images of three-dimensional flows in plastic microfluidic channels. The approach, called deconvolution microscopy, is achieved by (1) optically sectioning the flow in the microchannel by collecting a series of fluorescence images at different focal planes along the optical axis and (2) removing the out-of-focus fluorescence signal by a deconvolution method to reconstruct the corrected three-dimensional concentration image. We compare three different classes of deconvolution algorithms for a uniform concentration test case and then demonstrate how deconvolution microscopy is useful for flow visualization and analysis of mixing in microfluidic channels. In particular, we employ the method to confirm the presence of twisting flows in a microchannel containing microfabricated ridges. PMID- 17279729 TI - The chromophore structural changes during the photocycle of phytochrome: a combined resonance Raman and quantum chemical approach. AB - Phytochromes are sensory photoreceptors that, upon light irradiation, can be transformed between an inactive and an active state. The conversion is initiated by the photoisomerization of the cofactor, a linear methine-bridged tetrapyrrole, followed by conformational relaxations of the chromophore and the protein matrix that finally leads to the formation of the signaling state. To elucidate the underlying molecular processes, resonance Raman spectroscopy combined with quantum chemical calculations constitutes a powerful approach since it allows determination of the chromophore structure in the various states of phytochrome. On the basis of these studies, a molecular model for the photoinduced reaction cycle is derived. PMID- 17279730 TI - Comparison of DFT methods for molecular orbital eigenvalue calculations. AB - We report how closely the Kohn-Sham highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) eigenvalues of 11 density functional theory (DFT) functionals, respectively, correspond to the negative ionization potentials (-IPs) and electron affinities (EAs) of a test set of molecules. We also report how accurately the HOMO-LUMO gaps of these methods predict the lowest excitation energies using both time-independent and time-dependent DFT (TD-DFT). The 11 DFT functionals include the local spin density approximation (LSDA), five generalized gradient approximation (GGA) functionals, three hybrid GGA functionals, one hybrid functional, and one hybrid meta GGA functional. We find that the HOMO eigenvalues predicted by KMLYP, BH&HLYP, B3LYP, PW91, PBE, and BLYP predict the -IPs with average absolute errors of 0.73, 1.48, 3.10, 4.27, 4.33, and 4.41 eV, respectively. The LUMOs of all functionals fail to accurately predict the EAs. Although the GGA functionals inaccurately predict both the HOMO and LUMO eigenvalues, they predict the HOMO-LUMO gap relatively accurately (approximately 0.73 eV). On the other hand, the LUMO eigenvalues of the hybrid functionals fail to predict the EA to the extent that they include HF exchange, although increasing HF exchange improves the correspondence between the HOMO eigenvalue and -IP so that the HOMO-LUMO gaps are inaccurately predicted by hybrid DFT functionals. We find that TD-DFT with all functionals accurately predicts the HOMO-LUMO gaps. A linear correlation between the calculated HOMO eigenvalue and the experimental -IP and calculated HOMO-LUMO gap and experimental lowest excitation energy enables us to derive a simple correction formula. PMID- 17279731 TI - Calculated optoelectronic properties of ruthenium tris-bipyridine dyes containing oligophenyleneethynylene rigid rod linkers in different chemical environments. AB - Ruthenium tris-bipyridine dyes containing oligophenyleneethynylene (OPE) rigid rod linker groups ([Ru(bpy)3]2+, [Ru(bpy)2bpy-E-Ipa]2+, [Ru(bpy)2bpy-E-Ph-E Ipa]2+, and [Ru(bpy)2bpy-E-Bco-E-Ipa]2+, where bpy = 2,2'-bipyridine, E = ethynylene, Ph = p-phenylene, Bco = bicyclo[2.2.2]octylene, and Ipa = isophthalic acid) have been investigated using DFT and TD-DFT calculations to elucidate the influence of the rigid rod on their optoelectronic properties. Experimentally observed differences in the optical absorption for the different complexes are discussed on the basis of TD-DFT simulated absorption spectra. A comparison of the calculated optoelectronic properties of [Ru(bpy)2bpy-E-Ph-E-Ipa]2+ in different chemical environments, that is, in different solvents and with or without counter ions, suggests that both the absorption spectra and the redox properties of the dyes with OPE rods are sensitive to the environment. The calculations show that spurious low-energy charge-transfer excitations present in the TD-DFT calculations of the extended systems in vacuum are removed when the environment is included in the calculations. PMID- 17279732 TI - Enhancement of Structural fluctuation in the region connecting two kinds of critical points in temperature-pressure-composition three-dimensional phase diagram: Raman studies of benzene/CO2 binary systems up to supercritical region. AB - Pressure dependence of Raman spectra of benzene/CO2 two-component systems was systematically studied at different temperatures and compositions. We estimated the magnitude of inhomogeneous component in Raman bandwidth to get information on the structural fluctuation in the system. It was found that the inhomogeneous bandwidth attains a maximum on an isothermal plane in the temperature-pressure composition three-dimensional phase diagram when the state point crosses the line connecting the region where the density fluctuation is large (the vicinity of the critical point of neat CO2) and the region where the concentration fluctuation in a binary system is enhanced (the vicinity of the critical solution point). By accumulating such data, we found that the points of large structural fluctuation comprise a sheet that includes the extension line of the gas-liquid equilibrium line in the phase diagram of neat CO2 and the line connecting critical solution points of the two-component system at different temperatures. Interaction between benzene and CO2 molecules in the supercritical region is briefly discussed. PMID- 17279733 TI - Structure and dynamics of the aniline-argon complex as derived from its potential energy surface. AB - The structure and dynamics of the van der Waals (vdW) complex of aniline (An) with argon (Ar) are studied using ab initio methods. The inversion potential of the aniline-argon (AnAr) complex perturbed by the weak vdW interaction is calculated taking into account subtle corrections from the zero-point energy of the vdW modes and from the frequency shifts of the An normal modes modified by the complexation. The intermolecular potential energy surface (PES) of the AnAr complex is determined by performing a large-scale computation of the interaction energy and the fitting of the analytical many-body expansion to the set of single point interaction energies. The PES determined shows two deep local minima corresponding to the anti and syn AnAr conformers. The difference in the energies of these two minima is only 15 cm-1, but it is sufficient to localize the inversion wave functions and to form the two conformers. In the conformer anti (syn) of lower (higher) energy, Ar is bound to the An ring opposite (adjacent) the amino-hydrogens. In the additional local minima higher in energy, Ar approaches the aniline ring between the C-H bonds near its plane. An additional local minimum is located opposite of nitrogen between the two N-H bonds. The high energy minima are, however, too flat to form stable conformers. The perturbation of the interaction of Ar with the phenyl ring by the NH2 group is described by the vdW hole, which is responsible for unusually strong intermode mixing in the excited intermolecular vibrational states. The analysis of these states calculated for the ground (S0) as well as the first excited electronic state (S1) resolves difficulties faced earlier with the assignment of the observed vibronic bands of AnAr. PMID- 17279734 TI - Phosphorescent resonant energy transfer between iridium complexes. AB - The mechanism for triplet energy transfer from the green-emitting fac-tris[2-(4' tert-butylphenyl)pyridinato]iridium (Ir(tBu-ppy)3) complex to the red-emitting bis[2-(2'-benzothienyl)pyridinato-N,C3')(acetylacetonato)iridium (Ir(btp)2(acac)) phosphor has been investigated using steady-state and time-resolved photoluminescence spectroscopy. [2,2';5,'2' ']Terthiophene (3T) was also used as triplet energy acceptor to differentiate between the two common mechanisms for energy transfer, i.e., the direct exchange of electrons (Dexter transfer) or the coupling of transition dipoles (Forster transfer). Unlike Ir(btp)2(acac), 3T can only be active in Dexter energy transfer because it has a negligible ground state absorption to the 3(pi-pi*) state. The experiments demonstrate that in semidilute solution, the 3MLCT state of Ir(tBu-ppy)3 can transfer its triplet energy to the lower-lying 3(pi-pi*) states of both Ir(btp)2(acac) and 3T. For both acceptors, this transfer occurs via a diffusion-controlled reaction with a common rate constant (ken = 3.8 x 10(9) L mol-1 s-1). In a solid-state polymer matrix, the two acceptors, however, show entirely different behavior. The 3MLCT phosphorescence of Ir(tBu-ppy)3 is strongly quenched by Ir(btp)2(acac) but not by 3T. This reveals that under conditions where molecular diffusion is inhibited, triplet energy transfer only occurs via the Forster mechanism, provided that the transition dipole moments involved on energy donor and acceptor are not negligible. With the use of the Forster radius for triplet energy transfer from Ir(tBu-ppy)3 to Ir(btp)2(acac) of R0 = 3.02 nm, the experimentally observed quenching is found to agree quantitatively with a model for Forster energy transfer that assumes a random distribution of acceptors in a rigid matrix. PMID- 17279735 TI - Direct time-resolved study of the gas-phase reactions of germylene with ethyl- and diethylgermane: absolute rate constants, temperature dependences, and mechanism. AB - Time-resolved studies of germylene, GeH2, generated by the 193 nm laser flash photolysis of 3,4-dimethyl-1-germacyclopent-3-ene, have been carried out to obtain rate constants for its bimolecular reactions with ethyl- and diethylgermanes in the gas phase. The reactions were studied over the pressure range 1-100 Torr with SF6 as bath gas and at five temperatures in the range 297 564 K. Only slight pressure dependences were found for GeH2 + EtGeH3 (399, 486, and 564 K). The high pressure rate constants gave the following Arrhenius parameters: for GeH2 + EtGeH3, log A = -10.75 +/- 0.08 and Ea = -6.7 +/- 0.6 kJ mol-1; for GeH2 + Et2GeH2, log A = -10.68 +/- 0.11 and Ea = -6.95 +/- 0.80 kJ mol 1. These are consistent with fast, near collision-controlled, association processes at 298 K. RRKM modeling calculations are, for the most part, consistent with the observed pressure dependence of GeH2 + EtGeH3. The ethyl substituent effects have been extracted from these results and are much larger than the analogous methyl substituent effects in the SiH2 + methylsilane reaction series. This is consistent with a mechanistic model for Ge-H insertion in which the intermediate complex has a sizable secondary barrier to rearrangement. PMID- 17279737 TI - Nonempirical statistical theory for atomic evaporation from nonrigid clusters: applications to the absolute rate constant and kinetic energy release. AB - A high energy atomic cluster undergoing frequent structural isomerization behaves like a liquid droplet, from which atoms or molecules can be emitted. Even after evaporation, the daughter cluster may still keep changing its structure. We study the dynamics of such an evaporation process of atomic evaporation. To do so, we develop a statistical rate theory for dissociation of highly nonrigid molecules and propose a simple method to calculate the absolute value of classical phase space volume for a potential function that has many locally stable basins. The statistical prediction of the final distribution of the released kinetic energy is also developed. A direct application of the Rice-Ramsperger-Kassed-Marcus (RRKM) theory to this kind of multichannel chemical reaction is prohibitively difficult, unless further modeling and/or assumptions are made. We carry out a completely nonempirical statistical calculation for these dynamical quantities, in that nothing empirical is introduced like remodeling (or reparametrization) of artificial potential energy functions or recalibration of the phase-space volume referring to other "empirical" values such as those estimated with the molecular dynamics method. The so-called dividing surface is determined variationally, at which the flux is calculated in a consistent manner with the estimate of the phase-space volume in the initial state. Also, for the correct treatment of a highly nonrigid cluster, the phase-space volume and flux are estimated without the separation of vibrational and rotational motions. Both the microcanonical reaction rate and the final kinetic energy distribution thus obtained have quite accurately reproduced the corresponding quantities given by molecular dynamics calculations. This establishes the validity of the statistical arguments, which in turn brings about the deeper physical insight about the evaporation dynamics. PMID- 17279736 TI - Rapid and accurate estimation of densities of room-temperature ionic liquids and salts. AB - Volume parameters for room-temperature ionic liquids (RTILs) and salts were developed. For 59 of the most common imidazolium, pyridinium, pyrrolidinium, tetralkylammonium, and phosphonium-based RTILs, the mean absolute deviation (MAD) of the densities is 0.007 g cm-3; for 35 imidazolium-based room-temperature salts, the MAD is 0.020 g cm-3; and for 150 energetic salts, the MAD is 0.035 g cm-3. The experimental density (Y) for an alkylated imidazolium or pyridinium based room-temperature ionic liquid is approximately proportional to its calculated density (X) in the solid state: Y = 0.948X - 0.110 (correlation coefficient: R2 = 0.998, for BF4-, PF6-, NTf2- -containing ionic liquids); Y = 0.934X - 0.070 (correlation coefficient: R2 = 0.999, for OTf-, CF3CO2-, N(CN)2- containing ionic liquids). PMID- 17279738 TI - On the mechanism of gas-phase reaction of C1-C3 aliphatic thiols + OH radicals. AB - A theoretical study on the mechanism of the OH + aliphatic thiols reactions is presented. Optimum geometries and frequencies have been computed at the BHandHLYP/6-311++G(2d,2p) level of theory for all stationary points. Energy values have been improved by single-point calculations at the above geometries using CCSD(T)/6-311++G(d,p). Twelve possible channels have been modeled, three of them including the possible influence of molecular oxygen, and three of them involving excess of OH. The only channels that have been found to significantly contribute to the overall reaction in the troposphere are the hydrogen abstractions from the -SH group and from the alkyl groups. Our analysis supports a stepwise mechanism involving the formation of a short-lived, weakly bonded adduct in the entrance channel, for the abstraction paths. The results proposed in the present work seem to provide a viable explanation for diverse findings previously reported from experimental investigations. PMID- 17279739 TI - The effects of hydrogen-bonding environment on the polarization and electronic properties of water molecules. AB - Adequate representation of the interactions that take place between water molecules has long been a goal of force field design. A full understanding of how the molecular charge distribution of water is altered by adjacent water molecules and by the hydrogen-bonding environment is a vital step toward achieving this task. For this purpose we generated ab initio electron densities of pure water clusters and hydrated serine and tyrosine. Quantum chemical topology enabled the study of a well-defined water molecule inside these clusters, by means of its volume, energy, and multipole moments. Intra- and intermolecular charge transfer was monitored and related to the polarization of water in hydrogen-bonded networks. Our analysis affords a way to define different types of water molecules in clusters. PMID- 17279741 TI - Structural and spectroscopic evidence for the formation of trinuclear and tetranuclear vanadium(III)/carboxylate complexes of acetate and related derivatives in aqueous solution. AB - The formation of vanadium(III) complexes with nuclearity greater than two is believed to occur in aqueous solution on the basis of potentiometric, electrochemical, and/or UV-vis spectroscopy titration measurements, although structural evidence for this is limited. Upon the addition of 1-2 equiv of acetate, propionate, chloroacetate, trifluoroacetate, or bromoacetate to an aqueous, acidic solution of vanadium(III), trinuclear and tetranuclear complexes are formed. The structures of [V4(mu-OH)4(mu-OOCCF3)4(OH2)8]Cl4.7.5H2O (1), [V4(mu-OH)4(mu-OOCCH3)4(OH2)8]Cl4.CH3COOH.12H2O (2), [V4(mu-OH)4(mu OOCCH3)4(OH2)8]Cl4.3H2O (3), [V3(mu3-O)(mu-OOCCH2Br)6(OH2)3]CF3SO3.H2O (4), [V3(mu3-O)(mu-OOCCH2CH3)6(OH2)3]Cl.2H2O (5), [V3(mu3-O)(mu OOCCH3)6(OH2)3]Cl.3.5H2O (6), and [V3(mu3-O)(mu-OOCCH2Cl)6(OH2)3]CF3SO3.H2O (7) have been determined by X-ray diffraction. Importantly, electrospray mass spectrometry and 1H NMR measurements suggest that these complexes are not purely solid-state phenomena but are also present in solution. For the vanadium(III)/acetate and vanadium(III)/propionate systems, two paramagnetic 1H NMR signals corresponding to two distinct complexes (species A and B) are observed in the 40-55 ppm region for 0.20 mol equiv of acetate or propionate, at pD 3.44. No corresponding signals are observed for the vanadium(III)/bromoacetate and vanadium(III)/chloroacetate systems under the same conditions or for the vanadium(III)/ trifluoroacetate system using 19F NMR spectroscopy. UV-vis spectra suggest that species B are structurally analogous for the vanadium(III)/acetate and vanadium(III)/propionate systems, whereas structurally different complexes are the major species for the other systems. Diffusion coefficients of species B for the vanadium(III)/acetate and vanadium(III)/propionate systems determined by pulsed-field-gradient spin-echo NMR spectroscopy measurements are (3.0 +/- 0.1) x 10-6 and (3.23 +/- 0.01) x 10-6 cm2 s-1, respectively, and are most consistent with species B being trimeric, rather than tetranuclear, complexes. PMID- 17279740 TI - Potent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase. AB - A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5 position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-position with selected members approaching or exceeding the potency of 2f. Concurrent with these studies, the effect of substitution on the pyridine ring of 2f was also examined. A series of small, nonaromatic C5-substituents was also explored and revealed that the K(i) follows a well-defined correlation with the Hammett sigma(p) constant (rho = 3.01, R2 = 0.91) in which electron-withdrawing substituents enhance potency, leading to inhibitors with K(i)s as low as 400 pM (20n). Proteomic-wide screening of the inhibitors revealed that most are exquisitely selective for FAAH over all other mammalian proteases, reversing the 100-fold preference of 20a (C5 substituent = H) for the enzyme TGH. PMID- 17279742 TI - Synthesis, redox, and magnetic properties of a neutral, mixed-valent heptanuclear manganese wheel with S = 27/2 high-spin ground state. AB - Reaction of lithium tetrachloromanganate(II) with N-n-butyldiethanolamine H2L3 (3) in the presence of LiH leads to the formation of wheel-shaped, mixed-valent heptanuclear, neutral complex {MnII subset[MnII2MnIII4Cl6(L3)6]} (4). The manganese wheel crystallizes in the triclinic space group P as 4.2CHCl3 or 4.3THF when either diethyl ether or n-pentane was allowed to diffuse into solutions of 4 in chloroform or tetrahydrofuran. The oxidation states of each manganese ion in 4.2CHCl3 or 4.3THF were assigned on the basis of detailed symmetry, bond length, and charge considerations, as well as by the Jahn-Teller axial elongation observed for the manganese(III) ions, and were further supported by cyclic voltammetry. The analysis of the SQUID magnetic susceptibility data for complex 4.2CHCl3 showed that the intramolecular magnetic coupling of the manganese(II,III) ions is dominated by ferromagnetic exchange interactions. This results in an S = 27/2 ground-state multiplet at low magnetic field. At fields higher than 0.68 T, the energetically lowest state is given by the mS = 31/2 component of the S = 31/2 multiplet due to the Zeeman effect. The ligand-field splitting parameters were determined by anisotropy SQUID measurements on single crystalline samples along the crystallographic x, y, and z axes (D = -0.055 K, E = 6.6 mK) and by high-frequency electron spin resonance measurements on a polycrystalline powder of 4.2CHCl3 (D = -0.068 K, E = 9.7 mK). The resulting barrier height for magnetization reversal amounts to U approximately 10 K. Finally, 2DEG Hall magnetization measurements revealed that 4.2CHCl3 shows single molecule magnet behavior up to the blocking temperature of about 0.6 K with closely spaced steps in the hysteresis because of the quantum tunneling of the magnetization. PMID- 17279743 TI - Chelate control of diiron(I) dithiolates relevant to the [Fe-Fe]- hydrogenase active site. AB - The reaction of Fe2(S2C2H4)(CO)6 with cis-Ph2PCH=CHPPh2 (dppv) yields Fe2(S2C2H4)(CO)4(dppv), 1(CO)4, wherein the dppv ligand is chelated to a single iron center. NMR analysis indicates that in 1(CO)4, the dppv ligand spans axial and basal coordination sites. In addition to the axial-basal isomer, the 1,3 propanedithiolate and azadithiolate derivatives exist as dibasal isomers. Density functional theory (DFT) calculations indicate that the axial-basal isomer is destabilized by nonbonding interactions between the dppv and the central NH or CH2 of the larger dithiolates. The Fe(CO)3 subunit in 1(CO)4 undergoes substitution with PMe3 and cyanide to afford 1(CO)3(PMe3) and (Et4N)[1(CN)(CO)3], respectively. Kinetic studies show that 1(CO)4 reacts faster with donor ligands than does its parent Fe2(S2C2H4)(CO)6. The rate of reaction of 1(CO)4 with PMe3 was first order in each reactant, k = 3.1 x 10(-4) M(-1) s(-1). The activation parameters for this substitution reaction, DeltaH = 5.8(5) kcal/mol and DeltaS = 48(2) cal/deg.mol, indicate an associative pathway. DFT calculations suggest that, relative to Fe2(S2C2H4)(CO)6, the enhanced electrophilicity of 1(CO)4 arises from the stabilization of a "rotated" transition state, which is favored by the unsymmetrically disposed donor ligands. Oxidation of MeCN solutions of 1(CO)3(PMe3) with Cp2FePF6 yielded [Fe2(S2C2H4)(mu CO)(CO)2(dppv)(PMe3)(NCMe)](PF6)2. Reaction of this compound with PMe3 yielded [Fe2(S2C2H4)(mu-CO)(CO)(dppv)(PMe3)2(NCMe)](PF6)2. PMID- 17279745 TI - Hierarchical chiral framework based on a rigid adamantane tripod on Au(111). AB - We have investigated the tripod-shaped bromo adamantane trithiol (BATT) molecule on Au(111) using scanning tunneling microscopy (STM) at 4.7 K. Adsorption of BATT leads to formation of highly ordered self-assembled monolayers (SAMs) with three point contacts on Au(111). The structure of these SAMs has been found to have a two-tiered hierarchical chiral organization. The self-assembly of achiral monomers produces chiral trimers, which then act as the building blocks for chiral hexagonal supermolecules. SAMs begin to form from the racemic mixture of assembled molecules in ribbon-shaped islands, followed by the transformation to enantiomeric domains when SAM layers develop two-dimensionally across hcp domains. Such a chiral phase transition at the two-dimensional domain can arise from a subtle balance between molecule-substrate and intermolecular interactions. Two structural factors, the S atom (stabilization) and the methylene groups (chirality) located just above the S atom, induce the chiral ordering of BATT on Au(111). PMID- 17279744 TI - Conductivity in alkylamine/gold and alkanethiol/gold molecular junctions measured in molecule/nanoparticle/molecule bridges and conducting probe structures. AB - Charge transport through alkane monolayers on gold is measured as a function of molecule length in a controlled ambient using a metal/molecule/nanoparticle bridge structure and compared for both thiol and amine molecular end groups. The current through molecules with an amine/gold junction is observed to be more than a factor of 10 larger than that measured in similar molecules with thiol/gold linkages. Conducting probe atomic force microscopy is also used to characterize the same monolayer systems, and the results are quantitatively consistent with those found in the nanoparticle bridge geometry. Scaling of the current with contact area is used to estimate that approximately 100 molecules are probed in the nanoparticle bridge geometry. For both molecular end groups, the room temperature conductivity at low bias as a function of molecule length shows a reasonable fit to models of coherent nonresonant charge tunneling. The different conductivity is ascribed to differences in charge transfer and wave function mixing at the metal/molecule contact, including possible effects of amine group oxidation and molecular conformation. For the amine/Au contact, the nitrogen lone pair interaction with the gold results in a hybrid wave function directed along the molecule bond axis, whereas the thiol/Au contact leads to a more localized wave function. PMID- 17279746 TI - IR spectroscopy of Nb+(N2)n complexes: coordination, structures, and spin states. AB - Infrared photodissociation spectroscopy in the N-N stretching region is reported for gas-phase Nb+(N2)n complexes (n=3-16). The coordination of nitrogen to the metal cation causes the IR-forbidden N-N stretch of N2 to become active in these complexes. Fragmentation occurs by the loss of intact N2 molecules, and the yield as a function of laser wavelength produces an IR excitation spectrum. The dissociation patterns indicate that Nb+ has a coordination of six ligands. The infrared spectra for all complexes contain bands red-shifted from the N-N stretch in free nitrogen, consistent with ligand-metal charge-transfer interactions such as those familiar for metal carbonyl complexes. Using density functional theory, we investigated the structures and ground electronic states for each of the small cluster sizes. Theory indicates that binding to the low-spin triplet excited state of the metal ion becomes progressively more favorable than binding to its high-spin quintet ground state as additional ligands are added to the cluster. Although the quintet state is the ground state for the n=1-4 complexes, IR spectroscopy confirms that the low-spin triplet electronic state becomes the ground state for the n=5 and 6 complexes. The n=4 complex has a square-planar structure, familiar for high-spin d4 complexes in the condensed phase. The n=5 complex has a geometry that is nearly a square pyramid, while the n=6 complex has a structure close to octahedral. PMID- 17279747 TI - Triplet 1,3-diphenylpropynylidene (Ph-C-C-C-Ph). AB - Photolysis (lambda>571 nm) of 1,3-diphenyldiazopropyne (9) affords triplet 1,3 diphenylpropynylidene (3), as characterized by IR, UV/vis, and EPR spectroscopy in low-temperature matrices. Two conformational isomers of triplet 3 are spectroscopically distinguishable. The initially formed, non-relaxed conformer is believed to reflect the geometry of the diazo precursor, as enforced by the rigid matrix. Annealing the matrix permits the structure to relax to the equilibrium D2d geometry. The highly symmetric equilibrium structure of 3 is best envisioned as a 1,3-allenic diradical. Density functional theory calculations suggest that the equilibrium structure does not exhibit a bond-localized structure that would be characteristic of an acetylenic carbene. Chemical trapping with O2, however, affords products that are familiar as carbene trapping products: carbonyl oxide 10, ketone 11, and dioxirane 12. Irradiation (lambda>261 nm) of triplet 1,3 diphenylpropynylidene (3) results in cyclization to singlet diphenylcyclopropenylidene (6), a process that is photochemically reversible at lambda=232 nm. Diphenyl-1,2-propadienylidene (7) was not observed under any irradiation conditions. PMID- 17279748 TI - Filamentous phage studied by magic-angle spinning NMR: resonance assignment and secondary structure of the coat protein in Pf1. AB - Assignments are presented for resonances in the magic-angle spinning solid-state NMR spectra of the major coat protein subunit of the filamentous bacteriophage Pf1. NMR spectra were collected on uniformly 13C and 15N isotopically enriched, polyethylene glycol precipitated samples of fully infectious and hydrated phage. Site-specific assignments were achieved for 231 of the 251 labeled atoms (92%) of the 46-residue-long coat protein, including 136 of the 138 backbone atoms, by means of two- and three-dimensional 15N and 13C correlation experiments. A single chemical shift was observed for the vast majority of atoms, suggesting a single conformation for the 7300 subunits in the 36 MDa virion in its high-temperature form. On the other hand, multiple chemical shifts were observed for the Calpha, Cbeta, and Cgamma atoms of T5 in the helix terminus and the Calpha and Cbeta atoms of M42 in the DNA interaction domain. The chemical shifts of the backbone atoms indicate that the coat protein conformation involves a 40-residue continuous alpha-helix extending from residue 6 to the C-terminus. PMID- 17279749 TI - Glycosidase inhibition: an assessment of the binding of 18 putative transition state mimics. AB - The inhibition of glycoside hydrolases, through transition-state mimicry, is important both as a probe of enzyme mechanism and in the continuing quest for new drugs, notably in the treatment of cancer, HIV, influenza, and diabetes. The high affinity with which these enzymes are known to bind the transition state provides a framework upon which to design potent inhibitors. Recent work [for example, Bulow, A. et al. J. Am. Chem. Soc. 2000, 122, 8567-8568; Zechel, D. L. et al. J. Am. Chem. Soc. 2003, 125, 14313-14323] has revealed quite confusing and counter intuitive patterns of inhibition for a number of glycosidase inhibitors. Here we describe a synergistic approach for analysis of inhibitors with a single enzyme 'model system', the Thermotoga maritima family 1 beta-glucosidase, TmGH1. The pH dependence of enzyme activity and inhibition has been determined, structures of inhibitor complexes have been solved by X-ray crystallography, with data up to 1.65 A resolution, and isothermal titration calorimetry was used to establish the thermodynamic signature. This has allowed the characterization of 18 compounds, all putative transition-state mimics, in order to build an 'inhibition profile' that provides an insight into what governs binding. In contrast to our preconceptions, there is little correlation of inhibitor chemistry with the calorimetric dissection of thermodynamics. The ensemble of inhibitors shows strong enthalpy-entropy compensation, and the random distribution of similar inhibitors across the plot of DeltaH degrees a vs TDeltaS degrees a likely reflects the enormous contribution of solvation and desolvation effects on ligand binding. PMID- 17279750 TI - Effects of gas molecules on nanofluidic behaviors. AB - Most previous studies on nanofluidic motions were focused on liquid-solid interactions, with the important role of gas phase being ignored. Through a molecular dynamics simulation, we show that the gas-liquid interaction can be an indispensable factor in nanoenvironments. Gas molecules in relatively large nanochannels can be dissolved in the liquid during pressure-induced infiltration, leading to the phenomenon of "nonoutflow". By contrast, gas molecules tend to form clusters in relatively small nanochannels, which triggers liquid defiltration at a reduced pressure. The results qualitatively fit with the observations in a high-pressure-resting experiment on nanoporous silica gels. PMID- 17279751 TI - Synthesis of a ring-expanded bryostatin analogue. PMID- 17279753 TI - Acoustic emission spectra from 515 kHz cavitation in aqueous solutions containing surface-active solutes. AB - The effect of adding surface-active solutes to water being insonated at 515 kHz has been investigated by monitoring the acoustic emission from the solutions. At low concentrations (<3 mM), sodium dodecyl sulfate causes marked changes to the acoustic emission spectrum which can be interpreted in terms of preventing bubble coalescence and declustering of bubbles within a cavitating bubble cloud. By conducting experiments in the presence of background electrolytes and also using non-ionic surfactants, the importance of electrostatic effects has been revealed. The results provide further mechanistic evidence for the interpretation of the effect of surface-active solutes on acoustic cavitation and hence on the mechanism of sonochemistry. The work will be valuable to many researchers in allowing them to optimize reaction and process conditions in sonochemical systems. PMID- 17279752 TI - Total syntheses, fragmentation studies, and antitumor/antiproliferative activities of FR901464 and its low picomolar analogue. AB - FR901464 is a potent anticancer natural product that lowers the mRNA levels of oncogenes and tumor suppressor genes. In this article, we report a convergent enantioselective synthesis of FR901464, which was accomplished in 13 linear steps. Central to the synthetic approach was the diene-ene cross olefin metathesis reaction to generate the C6-C7 olefin without the use of protecting groups as the final step. Additional key reactions include a Zr/Ag-promoted alkynylation to set the C4 stereocenter, a mild and chemoselective Red-Al reduction, a reagent-controlled stereoselective Mislow-Evans-type [2,3] sigmatropic rearrangement to install the C5 stereocenter, a Carreira asymmetric alkynylation to generate the C4' stereocenter, and a highly efficient ring closing metathesis-allylic oxidation sequence to form an unsaturated lactone. The decomposition pathways of FR901464's right fragment were studied under physiologically relevant conditions. Facile epoxide opening by beta-elimination gave two enones, one of which could undergo dehydration via its hemiketal to form a furan. To prevent this decomposition pathway, a right fragment was rationally designed and synthesized. This analogue was 12 times more stable than the right fragment of the natural product. Using this more stable right fragment analogue, an FR901464 analogue, meayamycin, was prepared in 13 linear steps. The inhibitions of human breast cancer MCF-7 cell proliferation by synthetic FR901464 and meayamycin were studied, and the GI50 values for these compounds were determined to be 1.1 nM and 10 pM, respectively. Thus, meayamycin is among the most potent anticancer small molecules that do not bind to either DNA or microtubule. PMID- 17279754 TI - Fluorescent sequence-specific dsDNA binding oligomers. PMID- 17279755 TI - Asymmetric total syntheses of (+)-3-(z)-laureatin and (+)-3-(z)-isolaureatin by "lone pair-lone pair interaction-controlled" isomerization. AB - The first asymmetric total syntheses of the dihalogenated medium-sized dioxabicyclic marine natural products (+)-3-(Z)-isolaureatin (1) and (+)-3-(Z) laureatin (2) have been accomplished. Notable features of the highly stereo-, regio-, and chemoselective syntheses of these alpha,alpha'-trans-oxocene natural products include an intramolecular amide enolate alkylation to construct the alpha,alpha'-cis-oxocene, novel "lone pair-lone pair interaction-controlled" epimerizations to the alpha,alpha'-trans-oxocenes, various strategies for stereoselective introduction of halogen atoms, and novel olefin cross-metatheses for construction of the (Z)-enyne systems. PMID- 17279756 TI - Facile synthesis of highly pi-extended heteroarenes, dinaphtho[2,3-b:2',3' f]chalcogenopheno[3,2-b]chalcogenophenes, and their application to field-effect transistors. PMID- 17279757 TI - Forward and reverse electron transfer with the Y356DOPA-beta2 heterodimer of E. coli ribonucleotide reductase. PMID- 17279759 TI - Electrochemical generation of cationic Pd catalysts and application to Pd/TEMPO double-mediatory electrooxidative Wacker-type reactions. PMID- 17279758 TI - Synthesis of acyclic alpha,beta-unsaturated ketones via Pd(II)-catalyzed intermolecular reaction of alkynamides and alkenes. PMID- 17279760 TI - Electrophilic substitution of deep cavity cavitands: selective exo functionalization of molecular concavity. AB - [reaction: see text] The functionalization of deep-cavity cavitands via electrophilic substitution was investigated. In the parent structures, substitution occurs both at the exo position of the bowl-shaped hosts and on the convex face. Little or no endo substitution was observed. In contrast, derivatives in which methyl groups blocked the reaction sites on the convex face reacted selectively at the exo positions. PMID- 17279761 TI - A cascade reaction consisting of Pictet-Spengler-type cyclization and Smiles rearrangement: application to the synthesis of novel pyrrole-fused dihydropteridines. AB - [reaction: see text] Tandem Pictet-Spengler-type cyclization and Smiles rearrangement have been discovered in the synthesis of pyrimidine-fused heterocycles. The reaction of 4-chloro-5-pyrrol-1-ylpyrimidine amino aldehyde with an amine under an acidic condition yielded the Pictet-Spengler-type cyclization product diazepine, which readily underwent Smiles rearrangement to give a novel pyrrolo[1,2-f]pteridine derivative. PMID- 17279762 TI - Solid-phase synthesis and on-column deprotection of RNA from 2'- (and 3'-) O levulinated (Lv) ribonucleoside monomers. AB - [reaction: see text] The solid-phase synthesis of oligoribonucleotides derived from ribonucleosides esterified at the 2'- (or 3'-) position with the levulinyl (Lv) group is described. The oligomers can be released from the solid support as 2'-O-Lv ester derivatives or fully deprotected while still attached to the solid support. PMID- 17279763 TI - Efficient method for the synthesis of chiral pyrrolidine derivatives via ring closing enyne metathesis reaction. AB - [reaction: see text] A series of new pyrrolidine derivatives were prepared directly in very good yields, from the substrates containing a basic or nucleophilic N atom via ring-closing enyne metathesis reaction under mild reaction conditions. Moreover, the reaction occurs smoothly without the presence of ethylene gas. PMID- 17279764 TI - A new tandem reaction of benzyne: one-pot synthesis of aryl amines containing anthracene. AB - [reaction: see text] The reaction of benzyne with N-substituted imidazoles affords a novel way to prepare arylamines containing anthracene under very mild conditions. This transformation is assumed to proceed via a tandem reaction involving a Diels-Alder reaction and an intermolecular nucleophilic coupling reaction. PMID- 17279766 TI - Dynamic kinetic resolution of amines involving biocatalysis and in situ free radical mediated racemization. AB - [reaction: see text] The association of lipase-catalyzed enzymatic resolution with in situ racemization mediated with the thiyl radical enables the dynamic kinetic resolution of non-benzylic amines. It leads to (R)-amides with high enantioselectivities. It can be applied either to the conversion of racemic mixtures or to the inversion of (S)-enantiomers. PMID- 17279765 TI - Preparation and wittig reactions of organotrifluoroborato phosphonium ylides. AB - [reaction: see text] Potassium [(trifluoroboratophenyl)methyl]triphenylphosphonium chlorides have been prepared from the corresponding benzyl chlorides and PPh3. In the presence of 1.2 equiv of K2CO3 and various aldehydes, these mixed salts are easily converted to the corresponding unsaturated organotrifluoroborates via the intermediate phosphorus ylides. A protocol for a one-pot transformation has also been developed. PMID- 17279767 TI - In vitro interaction between ochratoxin A and different strains of Saccharomyces cerevisiae and Kloeckera apiculata. AB - The interaction of ochratoxin A (OTA) and 20 yeast strains of Saccharomyces cerevisiae and Kloeckera apiculata during alcoholic fermentation was studied. Levels of OTA were determined in the fermentation liquid and in the yeast cells solid using a high-performance liquid chromatography system with a fluorescence detector. Yeast cells do not adsorb OTA, and for all yeasts, OTA levels did not affect the alcoholic fermentation. Some yeast strains reduced levels of OTA, whereas other strains did not show any effect demonstrating that OTA level reduction is not a genus species characteristic but a strain trait. PMID- 17279768 TI - Tissue residues, metabolism, and excretion of radiolabeled sodium chlorate (Na[36Cl]O3) in rats. AB - A novel preharvest technology that reduces certain pathogenic bacteria in the gastrointestinal tracts of food animals involves feeding an experimental sodium chlorate-containing product (ECP) to animals 24-72 h prior to slaughter. To determine the metabolism and disposition of the active ingredient in ECP, four male Sprague-Dawley (approximately 350 g) rats received a single oral dose of sodium [36Cl]chlorate (3.0 mg/kg body weight). Urine, feces, and respired air were collected for 72 h. Radiochlorine absorption was 88-95% of the administered dose, and the major excretory route was the urine. Parent chlorate was the major species of radiochlorine present in urine at 6 h (approximately 98%) but declined sharply by 48 h (approximately 10%); chloride was the only other species of radiochlorine detected. Except for carcass remains (4.6% of dose), skin (3.2%), and gastrointestinal tract (1.3%), remaining tissues contained relatively low quantities of radioactivity, and >98% of radiochlorine remaining in the liver, kidney, and skeletal muscle was chloride. Chlorite instability was demonstrated in rat urine and bovine urine. The previously reported presence of chlorite in excreta of chlorate-dosed rats was shown to be an artifact of the analytical methods employed. Results from this study indicate that chlorate is rapidly absorbed and reduced to chloride, but not chlorite, in rats. PMID- 17279769 TI - Polyphenol content and antioxidative activity in some species of freshly consumed salads. AB - Ten genotypes belonging to Lactuca sativa, Cicorium intybus, Plantago coronopus, Eruca sativa, and Diplotaxis tenuifolia and used in fresh mixed salads were investigated for their polyphenol contents. Flavonoids and hydroxycinnamic acids were characterized by high-performance liquid chromatography (HPLC)/diode array detection/mass spectrometry. Quercetin, kaempferol, luteolin, apigenin, and crysoeriol derivatives were identified; hydroxycinnamic acids were all caffeoyl derivatives. The total polyphenol content was obtained through the Folin Ciocalteu test and from the HPLC data. The amounts ranged between 0.9 and 4.7 mg/g fresh weight. The antiradical activity was determined by the reaction with the stable DPPH* radical. The Fe2+ chelating activity was determined with a spectrophotometric test. From the complex of data, a quite complete picture of the characteristics of the vegetables emerges. A cultivated C. intybus cultivar exhibited the highest polyphenol content, while a wild C. intybus genotype exhibited the highest antiradical activity. In every case, the characteristics of the different salads as functional foods have been pointed out. PMID- 17279770 TI - Assessment of the differences in the phenolic composition of five strawberry cultivars (Fragaria x ananassa Duch.) grown in two different soilless systems. AB - The phenolics from different strawberry cultivars (Aromas, Camarosa, Diamante, Medina, and Ventana) cultivated in two different soilless systems (with and without recycling nutrient solution) were quantified to assess differences in their profiles as a function of both the variety and the cultivation system. Considering groups of phenols, it was found that either anthocyanins (including pelargonidin-3-glucoside, cyanidin-3-glucoside, pelargonidin-3-rutinoside, pelargonidin-3-acetylglucoside, and two unidentified pelargonidin derivatives) or phenolic acids (including caffeic, ferulic, p-coumaric, p-hydroxybenzoic, and ellagic acid) were quantitatively more important than those of flavonols (quercetin and kaempferol); the ranges of values were 78.81-198.88, 49.77-128.37, and 12.85-43.04 microg/g, respectively. Considering individual compounds and after applying relevant pattern recognition techniques, it was concluded that the contents of cyanidin-3-glucoside, pelargonidin-3-rutinoside, p-coumaric acid, and pelargonidin-3-glucoside were the most appropriate variables to discriminate among varieties, whereas those of p-hydroxybenzoic acid and pelargonidin derivative 1 were the most appropriate to discriminate between cultivation systems. The first factor of PCA was mainly linked to anthocyanins and quercetin, whereas the second principal component (PC) was related to kaempferol and p coumaric acid. PMID- 17279771 TI - Benzothiadiazole induces the accumulation of phenolics and improves resistance to powdery mildew in strawberries. AB - Benzothiadiazole (BTH) enhanced the accumulation of soluble and cell-wall-bound phenolics in strawberry leaves and also improved the resistance to powdery mildew infection under greenhouse conditions. The most pronounced change was seen in the levels of ellagitannins, which increased up to 2- to 6-fold 4 days after the BTH application, but persisted only in the inoculated plants. The induction of phenolic metabolism by BTH was also reflected in the fruits, several compounds being increased in inoculated, BTH-treated plants. Basal salicylic acid (SA) content was high in strawberry leaves, but increased in a similar fashion to other phenolics after the treatments. Several phenolic compounds were identified in strawberries for the first time. For example, ellagic acid deoxyhexose, three agrimoniin-like ellagitannins, sanguiin H-10- and lambertianin C-like ellagitannins in the leaves, ellagic acid, p-coumaric acid, gallic acid, and kaempferol hexose in the cell-wall-bound fraction of the leaves, and kaempferol malonylglucoside in the fruits. The findings show that BTH can enhance the accumulation of phenolics in strawberry plants which may then be involved in the BTH-induced resistance to powdery mildew. PMID- 17279772 TI - Cleavage of the C-terminal serine of human alphaA-crystallin produces alphaA1-172 with increased chaperone activity and oligomeric size. AB - This study aimed to study the oligomeric size, structure, hydrodynamic properties, and chaperone function of the C-terminally truncated human alphaA crystallin mutants with special emphasis on alphaA1-172 which is the cleavage product of the Ser172-Ser173 bond, unique to human lenses and constituting a major part of alphaA-crystallin. Various truncated forms of human alphaA crystallins were prepared by site-directed mutagenesis. The proteins were expressed in Escherichia coli BL21(DE3) pLysS cells and purified by size exclusion column chromatography. Molecular masses and the other hydrodynamic properties were determined by dynamic light scattering measurements. The secondary and tertiary structural changes were assessed by far- and near-UV CD spectra measurements, respectively. Chaperone activity was determined by using ADH, insulin, and betaL-crystallin as the target proteins. alphaAlpha1-172 exhibited a significant increase in oligomeric size, i.e., 866 kDa by light scattering measurements as compared to 702 kDa in alphaA-wt. alphaAlpha1-172 and alphaA-wt had similar secondary structure, but the former exhibited slightly altered tertiary structure. The most interesting observation was that alphaAlpha1 172 behaved as a 28-46% better chaperone than alphaA-wt. The oligomeric size and structure of alphaAlpha1-168 were similar to those of alphaA-wt, while the chaperone activity was decreased by 12-23%. alphaAlpha1-162, on the other hand, had an oligomeric size of 400 kDa, a decrease in chaperone activity of 80-100%, and significantly altered secondary and tertiary structures. The data show that the overall chaperone function of alphaA-crystallin will be significantly improved by the presence of the major truncated product alphaAlpha1-172. This will be beneficial to the lens undergoing oxidative stress. Since alphaAlpha1-168 and alphaAlpha1-162 are present only in small amounts, their effect would be minimal. PMID- 17279773 TI - DNA bending by charged peptides: electrophoretic and spectroscopic analyses. AB - We are testing the idea that placement of fixed charges near one face of the DNA double helix can induce DNA bending by a purely electrostatic mechanism. If stretching forces between DNA phosphates are significant, fixed charges should induce DNA bending by asymmetrically modulating these forces. We have previously tested this hypothesis by adding charged residues to small bZIP DNA binding peptides and monitoring DNA bending using electrophoretic phasing assays. Our results were consistent with an electrostatic model of DNA bending in predicted directions. We now confirm these observations with fluorescence resonance energy transfer (FRET). Using a "U"-shaped DNA probe, we report that DNA bending by charged bZIP peptides is readily detected by FRET. We further show that charged bZIP peptides cause DNA bending rather than DNA twisting. PMID- 17279774 TI - The kinetics of binding human prolactin, but not growth hormone, to the prolactin receptor vary over a physiologic pH range. AB - A member of the family of hematopoietic cytokines, human prolactin (hPRL) serves a dual role both as an endocrine hormone and as an autocrine/paracrine cytokine or growth factor. During investigation of the solution structural properties of hPRL, we have noted a surprising pH dependence of its structural stability over a range from approximately pH 6.0 to pH 8.0. An analysis of backbone atom NMR chemical shift changes and backbone amide hydrogen-deuterium exchange rates due to titration of the solution pH over this same range, along with calculations of protein surface electrostatic potential, suggests the possible involvement of a localized cluster of three His residues (27, 30, and 180), which comprise a portion of the high-affinity receptor-binding epitope. Surface plasmon resonance analysis of the interaction between hPRL and the extracellular domain (ECD) of the hPRL receptor reveals a selective 500-fold change in the dissociation rate between pH 8.3 and pH 5.8. In comparison, the interaction of hGH with the same receptor ECD did not demonstrate any significant dependence on pH. We also present an initial investigation of the pH dependence of hPRL function in rat Nb2 cell proliferation assays and a STAT5 luciferase gene reporter assay in the T47D human breast cancer cell line, whose results are consistent with our biophysical studies. The potential implications of this variation in hPRL's structural stability and receptor-binding kinetics over this physiologic range of pH are discussed. PMID- 17279775 TI - Biological and structural features of murine angiogenin-4, an angiogenic protein. AB - Murine angiogenin-4 (mAng-4) is a member of the pancreatic ribonuclease superfamily that is expressed in some endodermally derived organs. We now show that mAng-4 is angiogenic using a thoracic aorta assay never before applied to the angiogenins. mAng-4, human angiogenin (hAng), and murine angiogenin-1 (mAng 1) stimulate the proliferation of IGR1 melanoma cells but do not stimulate the proliferation or migration of bovine corneal endothelial cells or primary mouse embryonic fibroblasts. In addition, we report the 3-D structure of mAng-4 at 2.02 A resolution. The structure shows that the residues forming the putative B1, P1, and B2 RNA-binding subsites occupy positions similar to their hAng counterparts. The B1 subsite is obstructed by Glu115 and Ile118. The obstruction is stabilized by a novel salt bridge between the C-terminal carboxyl group and the side chain of Arg99. Through mutational studies, we identify residues critical to the angiogenic function of mAng-4. The effect of H12A and H112A mutations in the catalytic site indicates that ribonucleolytic activity is essential to angiogenesis. The consequences of a nearby E115A mutation are consistent with a significant role for Glu115 in the attenuation of enzymatic activity but also suggest that sufficient suppression of catalysis is necessary for angiogenesis. The effect of an R32A mutation in the putative nuclear localization sequence indicates that this residue is crucial for angiogenesis. In the putative cell binding segment, the replacement of Lys59 with Asn (its counterpart at position 61 of hAng) does not abrogate enzymatic activity but abolishes angiogenic activity, the reason for which is unclear. PMID- 17279776 TI - Design and characterization of a traceable protein kinase Calpha. AB - Protein kinase Calpha (PKCalpha) is a critical component of pathways that govern cancer-related phenotypes such as invasion and proliferation. Proteins that serve as immediate substrates for PKCalpha offer potential targets for anticancer drug design. To identify specific substrates, a mutant of PKCalpha (M417A) was constructed at the ATP binding site such that it could bind a sterically large ATP analogue derivatized through the N6 amino group of adenosine ([gamma-32P]-N6 phenyl-ATP). Because this analogue could be utilized by the mutant kinase but not by wild-type PKCalpha (or presumably other protein kinase) to phosphorylate peptide or protein substrates, 32P-labeled products were the direct result of the mutant PKCalpha. Kinetic analysis with [gamma-32P]-N6-phenyl-ATP revealed that the mutant retained undiminished affinity for the peptide substrate (Km = 12.4 microM) and a Vmax value (10.3 pmol/min) that was only 3-fold lower than that exhibited by the wild-type enzyme with natural ATP. However, with [gamma-32P]ATP, the mutant had a somewhat lower affinity (Km = 82.8 microM) than the wild-type enzyme (Km = 9.3 microM) in vitro but was competent in causing aggressive motility in nonmotile MCF-10A human breast cells (with endogenous ATP), as previously described for wild-type PKCalpha. The FLAG-tagged PKCalpha mutant was expressed in MCF-10A cells and used to co-immunoprecipitate high-affinity substrates from lysates. Immunopellets were reacted with [gamma-32P]-N6-phenyl ATP, and radiolabeled products were analyzed by SDS-PAGE and autoradiography. Mass spectrometry of selected bands identified several known substrates of PKC, thereby validating the methods used in these studies. These findings provide a foundation for future applications of this traceable PKCalpha mutant. PMID- 17279777 TI - Structural basis for spinophilin-neurabin receptor interaction. AB - Neurabin and spinophilin are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. However, thus far, it is still unknown how neurabin and spinophilin themselves are targeted to these membrane receptors. Spinophilin and neurabin contain a single PDZ domain, a common protein-protein interaction recognition motif, which are 86% identical in sequence. We report the structures of both the neurabin and spinophilin PDZ domains determined using biomolecular NMR spectroscopy. These proteins form the canonical PDZ domain fold. However, despite their high degree of sequence identity, there are distinct and significant structural differences between them, especially between the peptide binding pockets. Using two-dimensional 1H-15N HSQC NMR analysis, we demonstrate that C-terminal peptide ligands derived from glutamatergic AMPA and NMDA receptors and cytosolic proteins directly and differentially bind spinophilin and neurabin PDZ domains. This peptide binding data also allowed us to classify the neurabin and spinophilin PDZ domains as the first identified neuronal hybrid class V PDZ domains, which are capable of binding both class I and II peptides. Finally, the ability to bind to glutamate receptor subunits suggests that the PDZ domains of neurabin and spinophilin are important for targeting PP1 to C-terminal phosphorylation sites in AMPA and NMDA receptor subunits. PMID- 17279778 TI - Effects of heme pocket structure and mobility on cytochrome c stability. AB - Unfolding thermodynamics of a thermophilic cytochrome c552 from Hydrogenobacter thermophilus (Ht cyt c552) and its mesophilic homologue from Pseudomonas aeruginosa (Pa cyt c551) as well as two heme pocket point mutants (Ht-Q64N and Pa N64Q) are characterized by determination of protein stability curves (plots of unfolding free energy, DeltaG, vs T). These proteins show revealing differences in heme pocket hydrogen bonding and mobility. It previously has been shown that Asn64 in Pa cyt c551 and in Ht-Q64N interacts with the heme axial Met to fix it in a single conformation [Wen, X., and Bren, K. L. (2005) Biochemistry 44, 5225 5233]. In Ht cyt c552 and Pa-N64Q, Gln64 does not interact with the axial Met; in these variants the axial Met samples more than one conformation [Wen, X., and Bren, K. L. (2005) Inorg. Chem. 44, 8587-8593]. Here it is demonstrated that, relative to wild type, Pa-N64Q displays enhanced stability with an increase in unfolding free energy (DeltaDeltaG) of 7.1 kJ/mol and an increase in denaturation temperature (DeltaTm) of 8 degrees C. Correspondingly, Ht-Q64N is less stable than Ht cyt c552, with a DeltaDeltaG of -10 kJ/mol and a DeltaTm of -10 degrees C. Analysis of unfolding thermodynamics indicates that the net changes in stability resulting from the position 64 mutations are primarily attributable to entropic factors. For Pa-N64Q (Ht-Q64N) it is proposed that the favorable release (unfavorable burial) of residue 64 is the dominant factor impacting stability. The mobility of the axial Met also is proposed to contribute. These results provide a specific illustration of how amino acid side chain mobility and burial or release contribute to protein stability. PMID- 17279780 TI - Argon adsorption on Cu3(benzene-1,3,5-tricarboxylate)2(H2O)3 metal-organic framework. AB - Using volumetric adsorption techniques, we have measured the adsorption of argon on Cu3(BTC)2(H2O)3, (BTC = benzene-1,3,5-tricarboxylate), a microporous metal organic framework structure, at temperatures between 66 and 143 K. In addition to the experiments, we have used Grand Canonical Monte Carlo simulations to calculate the adsorption isotherm of argon at 87 K. Our experimental and theoretical results are compared to those of previous studies. The experiments were performed using a high density of points, allowing us to obtain, in detail, the isosteric heat's coverage dependence. Our values from the simulations are in reasonable agreement with those obtained in the experiments. PMID- 17279781 TI - Nanowear on polymer films of different architecture. AB - In this paper, we describe atomic force microscope (AFM) friction experiments on different polymers. The aim was to analyze the influence of the physical architecture of the polymer on the degree and mode of wear and on the wear mode. Experiments were carried out with (1) linear polystyrene (PS) and cycloolefinic copolymers of ethylene and norbornene, which are stabilized by entanglements, (2) mechanically stretched PS, (3) polyisoprene-b-polystyrene diblock copolymers, with varying composition, (4) brush polymers consisting of a poly(methyl methacrylate) (PMMA) backbone and PS side chains, (5) PMMA and PS brushes grafted from a silicon wafer, (6) plasma-polymerized PS, and (7) chemically cross-linked polycarbonate. For linear polymers, wear depends critically on the orientation of the chains with respect to the scan direction. With increasing cross-link density, wear was reduced and ripple formation was suppressed. The cross-linking density was the dominating material parameter characterizing wear. PMID- 17279779 TI - A comprehensive investigation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) metabolism in the mouse using a multivariate data analysis approach. AB - 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potent rodent carcinogen and a potential human carcinogen because of its existence in the normal human diet. N2-OH-PhIP, a major PhIP metabolite, has been identified as a precursor of genotoxic species. In vitro data supported the view that CYP1A2 is the major enzyme responsible for the formation of N2-OH-PhIP. However, disruption of the CYP1A2 gene in mouse failed to inhibit PhIP-induced carcinogenesis. To investigate the mechanism underlying this observation, the metabolism of PhIP in wild-type, Cyp1a2-null, and CYP1A2-humanized mice was examined in detail using a metabolomic approach. Following data acquisition in a high-resolution LC-MS system, urinary metabolomes of the control and PhIP-treated mice were characterized in a principal component analysis (PCA) model. Comprehensive metabolite profiles of PhIP in high dose (10 mg/kg) and low dose (100 microg/kg) were established through analyzing urinary ions contributing to the separation of three mouse lines in the multivariate model and by measuring radiolabled PhIP metabolite in a radio-HPLC assay, respectively. The genotoxicity of PhIP to three mouse lines was evaluated by measuring DNA adduction levels in liver, lung, colon, and mammary gland. On the basis of the chemical identities of 17 urinary PhIP metabolites, including eight novel metabolites, multivariate data analysis revealed the role of CYP1A2 in PhIP metabolism and a human-mouse interspecies difference in the catalytic activity of CYP1A2. In addition, the results also showed that Cyp1a2-null mice still possess significant N2-hydroxylation and DNA adduction activities, which may be partially attributed to mouse CYP2C enzymes according to the results from in vitro microsome and Supersome incubations and antibody inhibition experiments. PMID- 17279782 TI - Highly sensitive optical detection of humidity on polymer/metal nanoparticle hybrid films. AB - Porous metal films for optical humidity sensing were prepared from copper nanoparticles protected by a 2-3 nm carbon coating, a silicon tenside, and a polymeric wetting agent. Exposure to water or solvent vapor revealed an exceptional sensitivity with optical shifts in the visible light range of up to 50 nm for a change of 1% in relative humidity. These properties could be attributed to a combination of surface plasmon resonance effects at low humidity and thin film interference at higher water or solvent concentration in the surrounding air. The simple concept and use of ultra-low-cost materials suggests application of such porous metal-film-based optical humidity sensors in large scale applications for food handling, storage, and transport. PMID- 17279783 TI - Size-selective voltammetry: modification of the interface between two immiscible electrolyte solutions by zeolite Y. AB - Size- and charge-selective ion transfer across the zeolite-Y-modified interface between two immiscible electrolyte solutions (ZM-ITIES) is described. The zeolite Y membrane is prepared from pressed disks by healing with tetraethyl orthosilicate (TEOS). Size- and charge-selective transfer of the tetraethylammonium cation, size-selective exclusion of tetrabutylammonium cation, and charge-selective exclusion of the tetrafluoroborate and perchlorate anions are demonstrated at the ZM-ITIES. The exclusion studies suggest that the membrane is coherent and contains a low density of pinholes, after healing with TEOS. Various factors affecting the ion transfer such as analyte concentration, supporting electrolyte concentration, and scan rate are investigated. The diffusion coefficient of tetraethylammonium ions within the zeolite-Y pores is found to be on the order of 10(-8) cm2 s(-1). PMID- 17279784 TI - The stability of radio-frequency plasma-treated polydimethylsiloxane surfaces. AB - Polydimethylsiloxane (PDMS) is a widely used material for manufacturing lab-on chip devices. However, the hydrophobic nature of PDMS is a disadvantage in microfluidic systems. To transform the hydrophobic PDMS surface to hydrophilic, it was treated with radio-frequency (RF) air plasma at 150, 300, and 500 mTorr pressures for up to 30 min. Following the surface treatment, the PDMS specimens were stored in air, deionized water, or 0.14 M NaCl solution at 4 degrees C, 20 degrees C, and 70 degrees C. The change in the hydrophilicity (wettability) of the PDMS surfaces was followed by contact angle measurements and Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy as a function of time. As an effect of the RF plasma treatment, the contact angles measured on PDMS surfaces dropped from 113 +/- 4 degrees to 9 +/- 3 degrees . The chamber pressure and the treatment time had no or negligible effect on the results. However, the PDMS surface gradually lost its hydrophilic properties in time. The rate of this process is influenced by the difference in the dielectric constants of the PDMS and its ambient environment. It was the smallest at low temperatures in deionized water and largest at high temperatures in air. Apparently, the OH groups generated on the PDMS surface during the plasma treatment tended toward a more hydrophilic/less hydrophobic environment during the relaxation processes. The correlation between the FTIR-ATR spectral information and the contact angle data supports this interpretation. PMID- 17279785 TI - Impact of aluminum on the oxidation of lipids and enzymatic lipolysis in monomolecular films at the air/water interface. AB - There is evidence that serious pathologies are associated with aluminum (Al). In the present work, the influence of Al on enzymatic lipolysis was studied with the aim to get more insight into the possible link between the Al-induced membrane modification and the cytotoxicity of the trivalent cation (AlIII). Lipid monolayers were used as model membranes. The monomolecular film technique allowed monitoring the Al-dependent modifications of the lipid monolayer properties and enzyme kinetics. Two enzymes, namely, Candida rugosa lipase and a calcium (CaII) dependent phospholipase A2 from porcine pancreas, were used to catalyze the lipolysis of triglyceride and phosphoglyceride monolayers, respectively. The results obtained show that Al modifies both the monolayer structure and enzymatic reaction rates. While the enzymes used in this study can be considered as probes detecting lipid membrane properties, it cannot be excluded that in physiological conditions modulation of the enzyme action by the Al-bound membranes is among the reasons for Al toxicity. PMID- 17279786 TI - Immobilization of methylviologen between well-ordered multilayers of manganese oxide during their electrochemical assembly. AB - Methylviologen dications (MV2+) were immobilized between layers of manganese oxide during their electrochemical assembly by an anodic route in a homogeneous aqueous Mn2+ solution. This approach yielded a well-ordered multilayer film on a platinum substrate as a result of dense packing of planar MV2+ molecules to stabilize the layered framework. A grazing angle in-plane X-ray diffraction study revealed that the manganese oxide sheets and the molecular planes of inserted MV2+ ions are oriented parallel to the electrode surface. Cyclic voltammetry of the product film indicated an electron transfer from the underlying Pt substrate to inserted methylviologen ions through the manganese oxide sheets. PMID- 17279787 TI - Dispersion of thiol stabilized gold nanoparticles in lyotropic liquid crystalline systems. AB - A new method of forming stable dispersions of alkanethiol and aromatic thiol stabilized gold nanoparticles in two different lyotropic liquid crystalline mediums, namely, a columnar hexagonal phase made up of a Triton X-100/water system and an inverse columnar hexagonal phase made up of pure AOT, are presented. The dispersions have been characterized using small-angle X-ray scattering (SAXS) and polarizing optical microscopy. Our studies show that the gold nanoparticles are distributed outside the columns formed by both the surfactants. Such dispersions can find applications in the study of nanoparticles as well as in the development of devices based on some unique properties of metal nanoparticles. PMID- 17279789 TI - Role of nitrogen atom in aromatic stacking. AB - Aromatic stacking of 9,9'-(alpha,omega-alkanediyl)bis[adenine] (1), 1,1' (alpha,omega-alkanediyl)bis[benzimidazole] (2), and 9-[omega-(benzimidazol-1 yl)alkyl]adenine (3) were studied at low concentrations of these compounds by means of UV and NMR spectroscopies. The UV hypochromic effect at T degrees C was determined as the ratio of the integration strength B at T degrees C (T = 27, 40, and 50) to that at 60 degrees C. The UV hypochromic effects of 1 and 3 were remarkable in water, suggesting a formation of intramolecular aromatic stacking, while the UV data of 2 did not present unambiguous evidence supporting aromatic stacking. A difference of chemical shift of each aromatic ring proton between 27 and 80 degrees C, that is Deltadelta = delta(80 degrees C) - delta(27 degrees C), was given as an indication of the aromatic stacking in the NMR study. On the basis the data of Deltadelta, 1 and 3 were stabilized by a stacking interaction in the buffer solution at pD 7.0 but not in the organic solvents. On the other hand, the NMR data did not indicate the formation of aromatic stacking of 2 either in the organic solvents or in the aqueous solution. The thermodynamic parameters of the intramolecular aromatic stacking of 3 were determined by means of NMR spectroscopy. PMID- 17279788 TI - Synthesis and properties of cell-targeted Zn(II)-phthalocyanine-peptide conjugates. AB - Two Zn-Pc-peptide conjugates bearing either a short linker or a long PEG-linker between the macrocycle and a bifunctional peptide containing the nucleoplasmin and HIV-1 Tat 48-60 sequences have been synthesized in order to increase the Pc cell-targeting ability and to evaluate the effect of the linker. The presence of the peptide chain increased the water solubility of the Pc macrocycle and, consequently, its fluorescence in aqueous solutions. The highest fluorescence quantum yields were observed at low pH (5.0) for both conjugates and were always higher for the conjugate bearing the short linker. Both conjugates were found to have low dark cytotoxicity toward human HEp2 cells (IC50 > 77 microM) but were highly phototoxic (IC50 < 2 microM at 1 J cm-2). The conjugate bearing the long PEG-linker accumulated the most within cells (26 times more than the unconjugated Zn-Pc), followed by the short linker conjugate (17 times more than the unconjugated Zn-Pc). Both conjugates were found to localized preferentially within the cell lysosomes. PMID- 17279791 TI - Combined experimental and computational study of the thermochemistry of the fluoroaniline isomers. AB - The standard (p degrees = 0.1 MPa) molar enthalpies of formation in the condensed phase of all the fluoroanilines, with the exception of the 2,3,5-trifluoroaniline compound, were derived from the standard molar energies of combustion in oxygen at T = 298.15 K, measured by rotating bomb combustion calorimetry. Calvet high temperature vacuum sublimation experiments were performed to measure their enthalpies of vaporization or sublimation. These experiments allowed the determination of the standard molar enthalpies of formation in the gaseous phase and at T = 298.15 K. These values are also compared with estimates based on G3MP2B3 and BP86/6-31+G(d) computations, which have been extended also to the fluoroaniline that was not studied experimentally. The results are in close agreement with a mean deviation of approximately 3 kJ.mol-1. The largest difference between experimental and G3MP2B3 values is found for the pentafluoroaniline (-7.0 kJ.mol-1). For the three monofluoroanilines, the composite approach has been used also to compute gas-phase acidities, electron and proton affinities, ionization enthalpies and N-H bond dissociation enthalpies. The computed values compare well with available experimental results supporting the new computed data. PMID- 17279790 TI - The dielectric response of room-temperature ionic liquids: effect of cation variation. AB - In continuation of recent work on the dielectric response of imidazolium-based ionic liquids (ILs) (J. Phys. Chem. B, 2006, 110, 12682), we report on the effect of cation variation on the frequency-dependent dielectric permittivity up to 20 GHz of ionic liquids. The salts are comprised of pyrrolidinium, pyridinium, tetraalkylammonium, and triethylsulfonium cations combined with the bis ((trifluoromethyl)sulfonyl)imide anion. The dielectric spectra resemble those observed for imidazolium salts with the same anion. In all cases, the major contribution results from a diffusive low-frequency response on the time scale of several 100 ps, which shows a broadly distributed kinetics similar to that of spatially heterogeneous states in supercooled and glassy systems rather than that observed in fluid systems. There is evidence for a weak secondary process near 10 20 ps. Perhaps the most interesting difference to imidazolium salts is founded in the missing portions of the spectra due to processes beyond the upper cutoff frequency of 20 GHz. These are lower than that observed for imidazolium-based salts and seem to vanish for tetraalkylammonium and triethylsulfonium salts. As for imidazolium salts, the extrapolated static dielectric constants are on the order of epsilon(S) congruent with 10-13, classifying these ILs as solvents of moderate polarity. PMID- 17279792 TI - Photoinduced electron transfer reaction in room temperature ionic liquids: a combined laser flash photolysis and fluorescence study. AB - A detailed study of the photoinduced electron transfer (PET) reaction between pyrene and N,N-dimethylaniline has been made in four different room temperature ionic liquids (ILs) using steady state and time-resolved fluorescence and laser flash photolysis techniques. Unlike that in the conventional media, no exciplex emission for this well-known system could be observed in ILs. The rate constants for the PET induced quenching of the fluorescent state of pyrene, which lie between 6.9 and 37 x 107 M-1 s-1 depending on the viscosity, are found to be 2-4 times higher than the diffusion-controlled rates in ILs. The primary photoproducts of the PET process have been characterized by transient absorption spectroscopy, and the yields of the solvent-separated PET products have been determined. Even in the least viscous IL, [emim][Tf2N], the yield of the solvent separated radical ion is estimated to be only 0.015 +/- 0.005. In more viscous ILs such as [bmim][PF6], the yield is found to be so low that absorption due to these species could not be observed. The rate constant for the escape of the ionic products from the geminate ion pair in ILs has been estimated to be nearly 2-3 orders of magnitude lower than the back electron transfer rate. However, the small fraction of the PET products, which manage to escape geminate recombination, have been found to survive much longer compared to those in less viscous conventional solvents. PMID- 17279793 TI - Growth kinetics of 0.5 cm vertically aligned single-walled carbon nanotubes. AB - Half-centimeter-high mats of vertically aligned single-walled carbon nanotubes were grown at 600 degrees C by point-arc microwave plasma chemical vapor deposition. The mats were produced from 0.5 nm of an Fe catalyst layer, thus showing one of the highest catalytic yields of approximately 105 times. The growth process shows a lack of poisoning of the catalyst, in contrast to other reports. The experimental results confirm that the growth rate is ultimately limited by the gas phase diffusion of hydrocarbon radicals. PMID- 17279794 TI - Alpha-synuclein tertiary contact dynamics. AB - Tertiary contact formation rates in alpha-synuclein, an intrinsically disordered polypeptide implicated in Parkinson's disease, have been determined from measurements of diffusion-limited electron-transfer kinetics between triplet excited tryptophan:3-nitrotyrosine pairs separated by 10, 12, 55, and 90 residues. Calculations based on a Markovian lattice model developed to describe intrachain diffusion dynamics for a disordered polypeptide give contact quenching rates for various loop sizes ranging from 6 to 48 that are in reasonable agreement with experimentally determined values for small loops (10-20 residues). Contrary to expectations, measured contact rates in alpha-synuclein do not continue to decrease as the loop size increases (>/=35 residues), and substantial deviations from calculated rates are found for the pairs W4-Y94, Y39-W94, and W4 Y136. The contact rates for these large loops indicate much shorter average donor acceptor separations than expected for a random polymer. PMID- 17279796 TI - Biogenetic relationships between Annonaceous acetogenins: squamocin is not a precursor of chamuvarinin based on a semisynthetic study. AB - In the course of reactivity studies on squamocin (1), a highly cytotoxic acetogenin from the plant family Annonaceae, two diastereomers, 3 and 4, of chamuvarinin (2) were synthesized. Based on this, a plausible relative configuration was proposed for 2, demonstrating the absence of any biogenetic link between 1 and 2. The new analogues 3, 4, and 7 were also tested for their ability to induce apoptosis. PMID- 17279797 TI - Structures, biogenesis, and biological activities of pyrano[4,3-c]isochromen-4 one derivatives from the Fungus Phellinus igniarius. AB - Further chemical investigation of the Chinese medicinal fungus Phellinus igniarius has resulted in the isolation and structural elucidation of three pyrano[4,3-c]isochromen-4-one derivatives, phelligridins H (1), I (2), and J (3), together with the known compounds davallialactone (4), scopolin, nebularine, uridine, trehalose, glucitol, and ethyl glucoside. The structures of 1-3 were elucidated by spectroscopic methods. Phelligridins H (1) and I (2) possess unprecedented carbon skeletons, and phelligridin J (3) is an oxidative derivative of the co-occurring phelligridin A. Compounds 1 and 2 inhibited protein tyrosine phosphatase 1B (PTP1B) and rat liver microsomal lipid peroxidation, while compound 3 exhibited cytotoxic activity against several human cancer cell lines. PMID- 17279798 TI - Cytotoxic constituents from the fruiting branches of Callicarpa americana collected in southern Florida. AB - Bioassay-guided fractionation of the combined fruits, leaves, and twigs (fruiting branches) of Callicarpa americana, collected from a plot in a forested area in southern Florida, led to the isolation of six new clerodane diterpenes (1-6) and eight known compounds. The structures of 1-6 [12(S),16xi-dihydroxycleroda-3,13 dien-15,16-olide (1), 12(S)-hydroxy-16xi-methoxycleroda-3,13-dien-15,16-olide (2), 12(S)-hydroxycleroda-3,13-dien-15,16-olide (3), 16xi-hydroxycleroda 3,11(E),13-trien-15,16-olide (4), 3beta,12(S)-dihydroxycleroda-4(18),13-dien 15,16-olide (5), and 12(S)-hydroxycleroda-3,13-dien-16,15-olide (6)] were elucidated by interpretation of spectroscopic data and chemical methods. The absolute configuration at C-12 in 1 and 3 was ascertained using the Mosher ester technique. The cytotoxicity of all isolates was tested against a panel of human cancer cell lines, and compounds 1, 4, and 6, and the known compounds genkwanin, 16xi-hydroxycleroda-3,13-dien-15,16-olide, and 2-formyl-16xi-hydroxy-3-A norcleroda-2,13-dien-15,16-olide were active (ED50 <5 microg/mL). However, 1 was found to be inactive against human cancer cells implanted in mice using a hollow fiber tumor model. PMID- 17279800 TI - Nanoscale jet collision and mixing dynamics. AB - Micro- and macroscale investigations have shown that colliding drops always coalesce for small values of the Weber number We = rhoU2d/sigma. Our molecular dynamic simulations show that nanojets always recoil following head-on collision even though We --> 0. The duration between collision and recoil is a function of the nanojet impact velocity Uo and the nature of intermolecular interactions. Evaporation, which promotes mixing, occurs during recoil and is enhanced by reducing intermolecular interactions. Thereafter, mixing occurs through diffusion. The mixing dynamics are independent of Uo and the orifice shape. Consistent with a continuum analysis, the characteristic nanojet diameter at stagnation ds,1 proportional to Uo, recoil time following collision tau proportional to Uo-2, and the number of evaporating molecules N proportional to Uo. PMID- 17279801 TI - Atomic layer deposition on electrospun polymer fibers as a direct route to AL2O3 microtubes with precise wall thickness control. AB - Atomic layer deposition (ALD) of Al2O3 on electrospun poly(vinyl alcohol) microfiber templates is demonstrated as an effective and robust strategy by which to fabricate long and uniform metal-oxide microtubes. The wall thickness is shown to be precisely controlled within a molecular layer or so by adjusting the number of ALD cycles utilized. By judicious selection of the electrospinning and ALD parameters, designer tubes of various sizes and inorganic materials can be synthesized. PMID- 17279799 TI - Design, synthesis, and validation of a branched flexible linker for bioactive peptides. AB - A branched flexible linker that incorporates a fluorescent dansyl moiety was synthesized and used to connect two high affinity NDP-alpha-MSH ligands or two low affinity MSH(4) ligands. The linker was incorporated into the conjugate by solid-phase synthesis. In vitro biological evaluations showed that potency of binding to the human melanocortin 4 receptor was not diminished for linker-ligand combinations relative to the corresponding ligand alone. PMID- 17279802 TI - Plasmon resonances of a gold nanostar. AB - Using the finite-difference time-domain method, we show that the plasmons of a nanostar result from hybridization of plasmons of the core and tips of the nanoparticle. The nanostar core serves as a nanoscale antenna, dramatically increasing the excitation cross section and the electromagnetic field enhancements of the tip plasmons. Our analysis demonstrates that the plasmon hybridization picture can be combined with numerical approaches to interpret the physical origin of the plasmons of highly complex nanostructures. PMID- 17279803 TI - Intercalation of iodic acid into the layered uranyl iodate, UO2(IO3)2(H2O). AB - The direct intercalation of iodic acid into the layered uranyl iodate, UO2(IO3)2(H2O), has been observed to yield UO2(IO3)2(H2O).2HIO3 in crystalline form. This is the first example of this type of reaction with iodic acid. PMID- 17279804 TI - Catalytic promiscuity in biomimetic systems: catecholase-like activity, phosphatase-like activity, and hydrolytic DNA cleavage promoted by a new dicopper(II) hydroxo-bridged complex. AB - Presented in this Communication are the structure, physicochemical properties, and catalytic promiscuity of a new dinuclear CuII(mu-OH)CuII complex containing a novel N,O-donor symmetric dinucleating ligand. PMID- 17279805 TI - 1,2-HOIQO--a highly versatile 1,2-HOPO analogue. AB - A cyclic, bidentate hydroxamic acid binding unit based on an isoquinoline scaffold has been utilized for the synthesis of a hexadentate tripodal ligand based on the TREN backbone. This prototype for a new class of multidentate chelators forms mononuclear iron(III) complexes and one-dimensional coordination polymers with lanthanide(III) cations. The latter has been determined by single crystal X-ray analysis of the cerium species. The solid-state structure in the monoclinic space group P2(1)/c (C(36)H(34)CeN(7)O(11), a = 12.341(2) A, b = 26.649(4) A, c = 10.621(2) A, alpha = gamma = 90 degrees, beta = 96.753(3) degrees, V = 3468.6(9) A3, Z = 4) exhibits a trigonal-dodecahedral environment around the cerium cation. The proof of concept for the versatility of the new scaffold has been shown by the modification of the crucial precursor 3 carboxyisocoumarin through electrophilic aromatic substitutions to yield the corresponding chlorosulfonated and nitrated analogues. PMID- 17279806 TI - Which is reactive in alkaline solution, boronate ion or boronic acid? Kinetic evidence for reactive trigonal boronic acid in an alkaline solution. AB - That boronic acid is a reactive species toward a diol moiety even in an alkaline solution and that the boronate ion is not very reactive were demonstrated by the estimated upper limit of the rate constants for the reactions of some boronic acids with 2,2'-biphenol and 2,3-dihydroxynaphthalene in a neutral-alkaline solution, which will correct a common misunderstanding in boron chemistry and would renew the idea of effective boronic acid sensor design for carbohydrates. PMID- 17279807 TI - Reaction of the Mo3S4 cluster with dimethylacetylenedicarboxylate: an ESR-active cluster and an organometallic cluster formed by alpha,beta-conjugate addition. AB - A seven-electron cluster [Mo3(mu3-S){mu3-SC(CO(2)CH(3))=C(CO(2)CH(3))S}{mu SC(CO(2)CH(3))=CH(CO(2)CH(3))}(dtp)3(mu-OAc)] [2, S2P(OC(2)H(5))2-; dtp = diethyldithiophosphate] and an organometallic cluster [Mo3(mu3-S){mu3 SC(CO(2)CH(3))=C(CO(2)CH(3))S}{mu SC(CO(2)CH(3))CH(OCH(3))(CO2)}(dtp)2(CH(3)OH)(mu-OAc)](Mo-C) (3) were obtained by reaction in methanol of the sulfur-bridged trinuclear complex [Mo3(mu3-S)(mu S)3(dtp)3(CH(3)CN)(mu-OAc)] (1) with dimethylacetylenedicarboxylate (DMAD). The X ray structures of 2 and 3 revealed the adduct formation of two DMAD molecules to the respective Mo(3)S(4) cores. 2 is paramagnetic and obeys the Curie-Weiss law: the mu(eff) value at 300 K is 1.90 muB. The electron spin resonance signal was observed at 173 K. The density functional theory calculation of 2 demonstrated that the main components of the singly occupied molecular orbitals of alpha and beta spins are Mo d electrons and the main components of lowest unoccupied molecular orbitals are of Mo and the olefin moiety with one C-S bond. A one electron reversible oxidation process of 2 was observed at E1/2 = -0.11 V vs Fc/Fc+. The electronic spectrum of 2 has a peak at 468 nm (epsilon = 2170 M(-1) cm(-1)) and shoulders at 640 (918) and 797 (605) nm, and 3 has shoulders at 441 (1740) and 578 (625) nm and a distinct peak at 840 (467) nm. An intermediate [Mo3(mu3-S){mu3-SC(CO(2)CH(3))=C(CO(2)CH(3))S}{mu SC(CO(2)CH(3))=CH(CO(2)CH(3))}(dtp)3(mu-OAc)]+ (4) is tentatively suggested: a one-electron reduction of 4 gives 2, and a nucleophilic conjugate addition of CH(3)O- to the alpha,beta-unsaturated carbonyl group of 4 gives 3. PMID- 17279808 TI - Sterically bulky tris(triazolyl)borate ligands as water-soluble analogues of tris(pyrazolyl)borate. AB - The recently synthesized 3-tert-butyl-5-methyl-1,2,4-triazole reacted with KBH4 to give the new potassium tris(3-tert-butyl-5-methyl-1,2,4-triazolyl)borate K(Ttz(tBu,Me)) ligand. Ttz(tBu,Me) formed a four-coordinate (Ttz(tBu,Me))CoCl complex and five-coordinate (Ttz(tBu,Me))CoNO3 and (Ttz(tBu,Me))ZnOAc complexes. When these complexes were compared to their Tp(tBu,Me) analogues, it was found that Ttz(tBu,Me) resulted in negligible steric differences. K(Ttz(tBu,Me)) is more water-soluble than K(Tp(tBu,Me)), so bulky tris(triazolyl)borate ligands should lead to functional models for enzyme active sites in an aqueous environment and the creation of water-soluble analogues of Tp catalysts. PMID- 17279809 TI - Supramolecular rotor: adamantylammonium([18]crown-6) in [Ni(dmit)2]- salt. AB - Adamantylammonium (ADNH3+) was complexed with [18]crown-6, forming a supramolecular cation of (ADNH3+)([18]crown6), which was introduced into a [Ni(dmit)2]- salt as a supramolecular rotor. The cation layers were alternately arranged with [Ni(dmit)2]- layers in the crystal, in which the molecular rotation of (ADNH3+)([18]crown-6) was confirmed from the temperature-dependent solid-state 1H NMR. PMID- 17279810 TI - Chelating or bridging? Halide-controlled binding mode of diamido donor ligands in iron(III) complexes. AB - In a series of iron(III) halide complexes of the form {FeX[MesN(SiMe(2))]2O}2 (Mes = mesityl; X = Cl, Br, I), the ancillary diamidosilylether ligand can either chelate to one metal or instead bridge two metal centers, as a function of the halide coligand. The complexes are prepared from diamidosilyletheriron(II) precursors, which are oxidized with iodine, benzyl bromide, or PhICl2 to yield the appropriate iron(III) halide. The bromide analogue can also be synthesized by reacting the iron(II) precursor with a bromonium transfer agent (stabilized by adamantylideneadamantane). The latter reaction may proceed via an iron(IV) intermediate, which can oxidize the normally noncoordinating, inert [B(ArF)4]- counteranion [ArF = 3,5-(CF3)2Ph]. PMID- 17279811 TI - Formation of hollow Ni2p nanoparticles based on the nanoscale Kirkendall effect. AB - Colloidal hollow nanoparticles (NPs) of Ni2P have been prepared by a one-pot reaction from a mixture of nickel acetate, oleylamine, trioctylphosphine (TOP), and 1-octadecene. The mechanism to the hollow structure is related to the nanoscale Kirkendall effect. The process contains two important steps. First, oleylamine-stabilized Ni NPs were formed, which can protect them from TOP etching and slow down the inward diffusion of P atoms. Second, the solid-state reaction between the Ni NPs occurred when the TOP concentration and the reaction temperature were correctly adjusted. PMID- 17279812 TI - One-dimensional metal-organic framework with unprecedented heptanuclear copper units. AB - The reaction of copper(II) sulfate, copper(II) chloride, 3,5-diacetylamino-1,2,4 triazole, and 3-acetylamino-5-amino-1,2,4-triazole in water yields green, plate shaped crystals of [[{Cu3(mu3-OH(1/2))L(H2O)2Cl}2{mu-Cu(H2O)2Cl2}].12H2O]n (1), where L is a new triazole-derived macrocyclic ligand. The structure of 1 consists of heptanuclear (H)OCuII(3)-CuII-CuII(3)O(H) entities linked in pairs through symmetric mu3-O...H...O-mu3 hydrogen bonds to form a double-stranded one dimensional network. A significant overall antiferromagnetic behavior has been observed for 1. PMID- 17279813 TI - First insights into the electronic properties of a Cu(II) center embedded in the PN3 cap of a calix[6]arene-based ligand. AB - The first metal complex based on the calix[6]PN3 cryptand is described. The solid state and solution studies show a 5-coordinate Cu(II) center due to its coordination to the PN3 cap and to an exchangeable guest molecule. Spectroscopic and electrochemical studies evidence surprising properties of the metal ion, which are tentatively assigned to the unusual P-Cu(II) bond enforced by the cryptand. PMID- 17279814 TI - Investigation on the influence of particular structure parameters on the anisotropic spin-exchange interactions in the distorted wolframite-type oxides Cu(Mo(x)W(1-x))O4. AB - A spin-dimer analysis of the anisotropic spin-exchange interactions in the distorted wolframite-type oxides CuWO4, CuMoO4-III, and Cu(Mo(0.25)W(0.75))O4 was performed by Koo and Whangbo (Inorg. Chem. 2001, 40, 2161-2169). For Cu(Mo(0.25)W(0.75))O4, a magnetic structure with a magnetic unit cell doubled along the a and b axes has been predicted, but neutron powder diffraction on Cu(Mo(0.25)W(0.75))O4 did not confirm such a magnetic structure. In the present work, a detailed spin-dimer analysis, considering the influence of particular atomic structure parameters, finally revealed that a wrong coordinate transformation of the Cu z coordinate of the Cu(Mo(0.25)W(0.75))O4 structure is responsible for the prediction of the new, hypothetical magnetic structure. The deviation from the correct value is too small to be recognized by unreasonable bond lengths or angles but is sufficient to change one specific calculated value that is responsible for the prediction of the hypothetical magnetic structure. PMID- 17279815 TI - Synthesis of functionalized carboranes as potential anticancer and BNCT agents. AB - Carboranyl aldehydes react with alpha,beta-unsaturated esters, ketones, and nitriles in the presence of DABCO to provide functionalized carboranyl alcohols in good yields. Acetates of these alcohols undergo a facile isomerization with a variety of nucleophiles and afford structurally interesting carboranes. Biological evaluation of these molecules exhibited impressive antiproliferative activity for brain and breast cancer cells. PMID- 17279816 TI - Assignment of molecular structures to the electrochemical reduction products of diiron compounds related to [Fe-Fe] hydrogenase: a combined experimental and density functional theory study. AB - The reduction chemistry of (mu-bridge)[Fe(CO)3]2 [bridge = propane-1,3-dithiolate (1) and ethane-1,2-dithiolate (2)] is punctuated by the formation of distinct products, resulting in a marked difference in CO inhibition of electrocatalytic proton reduction. The products formed following reduction of 2 have been examined by a range of electrochemical, spectroelectrochemical, and spectroscopic approaches. Density functional theory has allowed assessment of the relative energies of the structures proposed for the reduction products and agreement between the calculated spectra (IR and NMR) and bond distances with the experimental spectra and EXAFS-derived structural parameters. For 1 and 2, one electron reduction is accompanied by dimerization, but the structure, stability, and reaction with CO of the dimer is different in the two cases, and this is responsible for the different CO inhibition response for electrocatalytic proton reduction. Calculations of the alternate structures of the two-electron, one proton reduced forms of 2 show that the isomers with terminally bound hydrides are unlikely to play a significant role in the chemistry of these species. The hydride-transfer chemistry of the 1B species is more reasonably attributed to a hydride-bridged form. The combination of experimental and computational results provides a solid foundation for the interpretation of the reduction chemistry of dithiolate-bridged diiron compounds, and this will underpin translation of the diiron subsite of the [FeFe] hydrogenase H cluster into an abiological context. PMID- 17279817 TI - Single- and two-photon properties of a dye-derivatized Roussin's red salt ester (Fe2(mu-RS)2(NO)4) with a large TPA cross section. AB - The synthesis, characterization, photochemistry, and two-photon photophysical properties of a new dye-derivatized iron sulfur nitrosyl cluster Fe2(mu-RS)2(NO)4 (AFX-RSE, RS = 2-thioethyl ester of N-phenyl-N-(3-(2-ethoxy)phenyl)-7 (benzothiazol-2-yl)-9,9-diethyl-fluoren-2-yl-amine) were investigated. Under continuous photolysis, AFX-RSE decomposes with modest quantum yields (Phi(diss) = (4.9 +/- 0.9) x 10(-3) at lambda(irr) = 436 nm) as measured from the loss of the nitrosyl bands in the IR absorbance spectrum. Nitric oxide (NO) was qualitatively demonstrated to be photochemically produced via single-photon excitation through the use of an NO-specific electrode. Steady-state luminescence measurements have shown that AFX-RSE fluorescence is about 88% quenched relative to the model compound AF-tosyl. This is attributed to a relatively efficient energy transfer from the excited states of the antenna chromophores to the dinuclear metal center, with the subsequent production of NO. In addition, the two-photon absorption (TPA) cross sections (delta) were measured for the AF-chromophores via the two-photon excitation (TPE) photoluminescence technique using a femtosecond excitation source. The TPA cross section of AFX-RSE was found with this technique to be delta = 246 +/- 8 GM (1 GM = 10(-50) cm4 s photon(-1) molecule(-1)). PMID- 17279818 TI - A metallacage encapsulating chloride as a probe for a solvation scale in ionic liquids. AB - With the purpose of assessing the reactivity of chloride ions dissolved in ionic liquids (ILs), a relative scale for the solvation of chloride is given for a series of ILs based on the bis(trifluoromethane)sulfonimide ([Tf(2)N]) anion and different cations, 1-butyl-3-methylimidazolium ([bmim]), 1-butyl-2,3 dimethylimidazolium ([bdmim]), 1-butyl-1-methylpyrrolidinium ([bmpy]), 1 butylpyridinium ([bpy]), 1-pentyl-1,1,1-triethylammonium ([C(5)e(3)am]), and 1-(2 hydroxy)ethyl-3-methylimidazolium ([mimeOH]). Insights into the solvation of chloride are achieved by the thermodynamic study of the reaction of dissociation of a chloride-templated nickel(II) metallacage performed at various temperatures by UV-visible spectroscopy in each IL. The order of chloride solvation [C(5)e(3)am][Tf(2)N] < [bmpy][Tf(2)N] < [bmim][Tf(2)N] [Fe(NO)(L)(L*)]0 (S = 1/2), [Fe(NO)(L)2]- (S = 0). Further one-electron reduction generates a dianion with an {FeNO}7 (S = 1/2) unit and two fully reduced, diamagnetic dianions L2-: [Fe(NO)(L)2]2- (S = 1/2). PMID- 17279833 TI - Multiple additions of phenylgermanium ligands to tetraruthenium and tetraosmium carbonyl cluster complexes. AB - Three new compounds, Ru4(mu4-GePh)2(mu-GePh2)2(mu-CO)2(CO)8 (11), Ru4(mu4 GePh)2(mu-GePh2)3(mu-CO)(CO)8 (12), and Ru4(mu4-GePh)2(mu-GePh2)4(CO)8 (13), were obtained from the reaction of H(4)Ru(4)(CO)12 with excess Ph(3)GeH in octane (11 and 12) or decane (13) reflux. Compound 11 was converted to compound 13 by reaction with Ph(3)GeH by heating solutions in nonane solvent to reflux. Compounds 11-13 each contain a square-type arrangement of four Ru atoms capped on each side by a quadruply bridging GePh ligand to form an octahedral geometry for the Ru(4)Ge(2) group. Compound 11 also contains two edge-bridging GePh(2) groups on opposite sides of the cluster and two bridging carbonyl ligands. Compound 12 contains three edge-bridging GePh(2) groups and one bridging carbonyl ligand. Compound 13 contains four bridging GePh(2) groups, one on each edge of the Ru4 square. The reaction of H(4)Os(4)(CO)12 with excess Ph(3)GeH in decane at reflux yielded two new tetraosmium cluster complexes, Os4(mu4-GePh)2(mu-GePh2)3(mu CO)(CO)8 (14) and Os4(mu4-GePh)2(mu-GePh(2))4(CO)8 (15). These compounds are structurally similar to compounds 12 and 13, respectively. PMID- 17279834 TI - 63Cu NMR spectroscopy of copper(I) complexes with various tridentate ligands: CO as a useful 63Cu NMR probe for sharpening 63Cu NMR signals and analyzing the electronic donor effect of a ligand. AB - 63Cu NMR spectroscopic studies of copper(I) complexes with various N-donor tridentate ligands are reported. As has been previously reported for most copper(I) complexes, 63Cu NMR signals, when acetonitrile is coordinated to copper(I) complexes of these tridentate ligands, are broad or undetectable. However, when CO is bound to tridentate copper(I) complexes, the 63Cu NMR signals become much sharper and show a large downfield shift compared to those for the corresponding acetonitrile complexes. Temperature dependence of 63Cu NMR signals for these copper(I) complexes show that a quadrupole relaxation process is much more significant to their 63Cu NMR line widths than a ligand exchange process. Therefore, an electronic effect of the copper bound CO makes the 63Cu NMR signal sharp and easily detected. The large downfield shift for the copper(I) carbonyl complex can be explained by a paramagnetic shielding effect induced by the copper bound CO, which amplifies small structural and electronic changes that occur around the copper ion to be easily detected in their 63Cu NMR shifts. This is evidenced by the correlation between the 63Cu NMR shifts for the copper(I) carbonyl complexes and their nu(C[triple bond]O) values. Furthermore, the 63Cu NMR shifts for copper(I) carbonyl complexes with imino-type tridentate ligands show a different correlation line with those for amino-type tridentate ligands. On the other hand, 13C NMR shifts for the copper bound 13CO for these copper(I) carbonyl complexes do not correlate with the nu(C[triple bond]O) values. The X ray crystal structures of these copper(I) carbonyl complexes do not show any evidence of a significant structural change around the Cu-CO moiety. The findings herein indicate that CO complexation makes 63Cu NMR spectroscopy much more useful for Cu(I) chemistry. PMID- 17279836 TI - Temperature-dependent coordination of phosphine to five-coordinate alkenylruthenium complexes. AB - The red, five-coordinate complexes Ru(CO)Cl(PPh(3))2(CH=CHPh) and [Ru(CO)Cl(PPh(3))2]2(mu-CH=CHC(6)H(4)CH=CH) undergo reversible coordination of PPh(3) at low temperature to produce the pale yellow, six-coordinate complexes Ru(CO)Cl(PPh(3))3(CH=CHPh) and [Ru(CO)Cl(PPh(3))3]2(mu-CH=CHC(6)H(4)CH=CH). X-ray crystal structures of the latter complex and of the hydride complex RuH(CO)Cl(PPh(3))3 were obtained. 1H and 31P NMR spectra between 20 and -70 degrees C exhibit large changes in both equilibrium constants and dynamic effects. Thermodynamic parameters, DeltaH = -17.5 +/- 2.0 kcal/mol and DeltaS = 57.5 +/- 7.6 eu, were obtained for PPh(3) coordination to the monoruthenium complex, and activation parameters, DeltaH = 20.6 +/- 0.7 kcal/mol and DeltaS = 41.6 +/- 2.0 eu, were obtained for the reverse decoordination. Coordination of PPh(3) was not observed upon cooling of the shorter bridged complex, [Ru(CO)Cl(PPh(3))2]2(mu-CH=CHCH=CH). PMID- 17279835 TI - Mixed Co-Rh nitrido-encapsulated carbonyl clusters. synthesis, solid-state structure, and electrochemical/EPR characterization of the anions [Co10Rh(N)2(CO)21]3-, [Co10Rh2(N)2(CO)24]2-, and [Co11Rh(N)2(CO)24]2-. AB - The nitrido-encapsulated heterometallic cluster anions [Co(10)Rh(N)2(CO)21](3-) (1), [Co(10)Rh2(N)2(CO)24](2-) (2), and [Co(11)Rh(N)2(CO)24](2-) (3) have been obtained by tailored redox-condensation reactions. These three anions are rare high-nuclearity mixed-metal clusters containing two interstitial nitrogen atoms. Their structures have been determined by single-crystal X-ray diffraction on their [NR4]+ salts (R = Me for 1 and 3, R = Et for 2), and their electrochemical and ESR properties have been studied in detail. It is noteworthy that 1 has an unprecedented stereochemistry that does not exhibit a close geometrical resemblance with the isoelectronic homometallic anion [Co(11)N2(CO)11(mu2 CO)10](3-), and 2, despite its even number of electrons, is a paramagnetic species. PMID- 17279837 TI - 1H NMR direct observation of enantiomeric exchange in palladium(II) and platinum(II) complexes containing N,N' bidentate aryl-pyridin-2-ylmethyl-amine ligands. AB - The complexes [MCl(2)(kappa2-N approximately N')] (N approximately N' = 2 C(5)H(4)N-CH2-NHAr; Ar = 4-MeC(6)H(4), a; 2,6-Me(2)C(6)H(3), b; 4-MeOC(6)H(4), c; 4-CF(3)C(6)H(4), d; M = Pd, 1a-d; Pt, 2a-d) have been prepared and fully stereochemically characterized both in the solid state and in solution. Their behavior in DMSO-d6 solution is dependent on the substituents of the aryl group and on the metal. Complexes of palladium with substituents at the para position (1a, 1c, 1d) display a dynamic 1H NMR pattern when the solutions are heated. An enantiomeric exchange Slambda/Rdelta is suggested to explain such behavior. On the basis of the calculated negative DeltaS values, an associative mechanism involving the solvent is proposed. Under the same conditions, analogous complexes of platinum (2a, 2c, 2d) proved to be unstable, and release of the N approximately N' ligand was observed. Complexes 1b and 2b show temperature variable 1H NMR spectra without any evidence accounting for enantiomeric exchange or decoordination. DFT calculations on models of 1a and 1b show that diastereomeric exchange Sdelta/Slambda is a process where the complex with the higher sterical hindrance, 1b, has a lower energy barrier. PMID- 17279838 TI - ESR, zero-field splitting, and magnetic exchange of exchange-coupled copper(II) copper(II) pairs in copper(II) tetraphenylporphyrin N-oxide. AB - The crystal structures of the dimer form of copper(II) tetraphenylporphyrin N oxide, [Cu(tpp-N-O)]2 (3-dimer), and zinc(II) tetraphenylporphyrin N-oxide, [Zn(tpp-N-O)]2 (4-dimer), were established. The geometry at the copper ion in 3 dimer is essentially square-pyramidal with one oxygen bridge [O(1A)] occupying the apical site, giving a much larger Cu-O bond distance compared to those at the basal plane. The respective Cu...Cu distance and Cu-O-Cu angle in the core of 3 dimer are 3.987(4) A and 148.1(3) degrees. The Zn(1) atom in 4-dimer has a distorted square-pyramidal [4 + 1] coordination geometry that gives a tau-value of 0.19. The respective Zn...Zn distance and Zn-O-Zn angle in the dimeric unit of 4-dimer are 4.025(3) A and 148.1(2) degrees. The 3-dimer displays axial X-band electron paramagnetic resonance spectral features (Es = 0) in the powder state at 4 K, giving g parallel = 2.51 (A(parallel,s) = (9.6 +/- 0.2) x 10-3 cm(-1)) and g(perpendicular) = 2.11 and in the same powder state at 293 K giving Ds = 0.0731 cm(-1) (as derived from DeltaMs = 1 lines) or 0.0743 cm(-1) (as derived from the DeltaMs = 2 lines). In addition, 3-dimer displays a DeltaMs = 2 transition at g = 4.17 indicating the presence of spin-exchange coupling. The anisotropic exchange interaction (Ds(ex)= 0.132 cm(-1)) gives the main contribution to Ds in 3-dimer. The theoretical fit of the susceptibility and effective magnetic moment data of 3 dimer in the temperature range of 5-300 K gives 2J = 68 cm(-1), g = 2.01, p = 0.06, and a temperature-independent paramagnetism of 10(-6) cm3 mol(-1). This magnetic susceptibility data indicates that the copper(II) ions in 3-dimer are coupled in a ferromagnetic manner with the ground-spin triplet stabilized by 68 cm(-1) with regard to the singlet. PMID- 17279839 TI - Syntheses and characterizations of bismuth nanofilms and nanorhombuses by the structure-controlling solventless method. AB - Substrate-free bismuth nanofilms with an average thickness of 0.6 nm (sigma = +/ 14.1%) and monodisperse layered Bi nanorhombuses with an average edge length of 21.5 nm (sigma = +/-14.7%) and thickness of 0.9 nm (sigma = +/-25.8%) have been successively synthesized by structure-controlling solventless thermolysis from a new layered bismuth thiolate precursor with a 31.49 A spacing. The morphologies result from self-control at an atomic level by the layered Bi(SC(12)H(25))3 crystal structure. The formation of the Bi nanofilm intermediate provides significant substantiation for this synthesis method, and detailed evidence on the conversion progress has been obtained. Both the films and the rhombuses have been characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), energy-dispersive X-ray spectrometry (EDX), high-resolution TEM (HRTEM), and atomic force microscopy (AFM) measurements. Special UV-vis electronic absorption spectra of the nanoproducts have been studied. PMID- 17279840 TI - Mechanism and driving force of NO transfer from S-nitrosothiol to cobalt(II) porphyrin: a detailed thermodynamic and kinetic study. AB - The thermodynamics and kinetics of NO transfer from S nitrosotriphenylmethanethiol (Ph(3)CSNO) to a series of alpha,beta,gamma,delta tetraphenylporphinatocobalt(II) derivatives [T(G)PPCoII], generating the nitrosyl cobalt atom center adducts [T(G)PPCoIINO], in benzonitrile were investigated using titration calorimetry and stopped-flow UV-vis spectrophotometry, respectively. The estimation of the energy change for each elementary step in the possible NO transfer pathways suggests that the most likely route is a concerted process of the homolytic S-NO bond dissociation and the formation of the Co-NO bond. The kinetic investigation on the NO transfer shows that the second-order rate constants at room temperature cover the range from 0.76 x 10(4) to 4.58 x 10(4) M(-1) s(-1), and the reaction rate was mainly governed by activation enthalpy. Hammett-type linear free-energy analysis indicates that the NO moiety in Ph(3)CSNO is a Lewis acid and the T(G)PPCoII is a Lewis base; the main driving force for the NO transfer is electrostatic charge attraction rather than the spin spin coupling interaction. The effective charge distribution on the cobalt atom in the cobalt porphyrin at the various stages, the reactant [T(G)PPCoII], the transition-state, and the product [T(G)PPCoIINO], was estimated to show that the cobalt atom carries relative effective positive charges of 2.000 in the reactant [T(G)PPCoII], 2.350 in the transition state, and 2.503 in the product [T(G)PPCoIINO], which indicates that the concerted NO transfer from Ph(3)CSNO to T(G)PPCoII with the release of the Ph(3)CS* radical was actually performed by the initial negative charge (-0.350) transfer from T(G)PPCoII to Ph(3)CSNO to form the transition state and was followed by homolytic S-NO bond dissociation of Ph(3)CSNO with a further negative charge (-0.153) transfer from T(G)PPCoII to the NO group to form the final product T(G)PPCoIINO. It is evident that these important thermodynamic and kinetic results would be helpful in understanding the nature of the interaction between RSNO and metal porphyrins in both chemical and biochemical systems. PMID- 17279843 TI - The nonconscious cessation of goal pursuit: when goals and negative affect are coactivated. AB - Extending on the recent investigation into the implicit affective processes underlying motivation and decision making, 5 studies examined the role of negative affect in moderating goal priming effects. Specifically, experimental effects on measures that typify motivational qualities of goal systems, such as keeping a goal at a heightened level of mental accessibility and exerting effort to work for a goal and experiencing desire to attain the goal, showed that the motivation and resultant operation of social goals cease when these goals are primed in temporal proximity of negatively valenced information. These goal cessation effects resulting from the mere coactivation of a goal and negative affect are discussed against the background of present research on nonconscious goal pursuit and the role of accessibility and desirability in the regulation of automatic goal-directed behavior. PMID- 17279844 TI - The confounded nature of angry men and happy women. AB - Findings of 7 studies suggested that decisions about the sex of a face and the emotional expressions of anger or happiness are not independent: Participants were faster and more accurate at detecting angry expressions on male faces and at detecting happy expressions on female faces. These findings were robust across different stimulus sets and judgment tasks and indicated bottom-up perceptual processes rather than just top-down conceptually driven ones. Results from additional studies in which neutrally expressive faces were used suggested that the connections between masculine features and angry expressions and between feminine features and happy expressions might be a property of the sexual dimorphism of the face itself and not merely a result of gender stereotypes biasing the perception. PMID- 17279845 TI - Epistemic motives and cultural conformity: need for closure, culture, and context as determinants of conflict judgments. AB - Three studies support the proposal that need for closure (NFC) involves a desire for consensual validation that leads to cultural conformity. Individual differences in NFC interact with cultural group variables to determine East Asian versus Western differences in conflict style and procedural preferences (Study 1), information gathering in disputes (Study 2), and fairness judgment in reward allocations (Study 3). Results from experimental tests indicate that the relevance of NFC to cultural conformity reflects consensus motives rather than effort minimization (Study 2) or political conservatism (Study 3). Implications for research on conflict resolution and motivated cultural cognition are discussed. PMID- 17279846 TI - What do people desire in others? A sociofunctional perspective on the importance of different valued characteristics. AB - Humans, as discriminately social creatures, make frequent judgments about others' suitability for interdependent social relations. Which characteristics of others guide these judgments and, thus, shape patterns of human affiliation? Extant research is only minimally useful for answering this question. On the basis of a sociofunctional analysis of human sociality, the authors hypothesized that people highly value trustworthiness and (to a lesser extent) cooperativeness in others with whom they may be interdependent, regardless of the specific tasks, goals, or functions of the group or relationship, but value other favorable characteristics (e.g., intelligence) differentially across such tasks, goals, or functions. Participants in 3 studies considered various characteristics for ideal members of interdependent groups (e.g., work teams, athletic teams) and relationships (e.g., family members, employees). Across different measures of trait importance and different groups and relationships, trustworthiness was considered extremely important for all interdependent others; the evidence for the enhanced importance of cooperativeness across different interdependence contexts was more equivocal. In contrast, people valued other characteristics primarily as they were relevant to the specific nature of the interdependent group or relationship. These empirical investigations illuminate the essence of human sociality with its foundation of trust and highlight the usefulness of a theoretically derived framework of valued characteristics. PMID- 17279847 TI - More than words: reframing compliments from romantic partners fosters security in low self-esteem individuals. AB - Although people with low self-esteem (LSEs) doubt their value to their romantic partners, they tend to resist positive feedback from their partners. This resistance undermines their relationships and has been difficult to overcome in past research. The authors investigated whether LSEs could be induced to take their partners' kind words to heart by manipulating how abstractly they described a recent compliment. In 3 studies, LSEs felt more positively about the compliments, about themselves, and about their relationships--as positively as people with high self-esteem (HSEs) felt--when they were encouraged to describe the meaning and significance of the compliments. The effects of this abstract meaning manipulation were still evident 2 weeks later. Thus, when prompted, LSEs can reframe affirmations from their partners to be as meaningful as HSEs generally believe them to be and, consequently, can feel just as secure and satisfied with their romantic relationships. PMID- 17279848 TI - Why some groups just feel better: the regulatory fit of group power. AB - The current research applied the regulatory fit hypothesis (E. T. Higgins, 2000) to the evaluation of groups, suggesting that individuals' group appraisal depends on how well the groups fit their regulatory needs. Specifically, it was predicted that higher power groups would fit and be more valued by those individuals with a promotion focus because these groups provide a better opportunity to sustain nurturance and achievement needs. Alternatively, lower power groups were predicted to fit and be more valued by those individuals with a prevention focus because these groups necessitate (and thus sustain) a focus on safety and security. Five studies found support for these predictions by both assessing and manipulating regulatory focus and group power and by using explicit and implicit measures of group attraction. Moreover, these regulatory fit effects occurred specifically for group power and not for general differences in group status. PMID- 17279850 TI - Metaperceptions of bias in intimate relationships. AB - Meta-awareness of bias in intimate partner judgments was investigated in 3 studies. In Study 1, participants rated fictional partners in happier relationships as more positively biased in their partner perceptions. In Study 2, participants thought their judgments of their own current partners were positively biased and that they were judged by their partners in a positively biased fashion. Using a sample of couples, Study 3 showed that metaperceptions of bias were anchored to actual levels of bias at the individual and relationship levels. In addition, positive bias was accentuated for traits that were more relevant to mate evaluation. These findings (as expected) suggest that positive bias in partner judgments can be a normative and consciously accessible feature of intimate relationships. PMID- 17279849 TI - The dependency paradox in close relationships: accepting dependence promotes independence. AB - Using multiple methods, this investigation tested the hypothesis that a close relationship partner's acceptance of dependence when needed (e.g., sensitive responsiveness to distress cues) is associated with less dependence, more autonomous functioning, and more self-sufficiency (as opposed to more dependence) on the part of the supported individual. In two studies, measures of acceptance of dependency needs and independent functioning were obtained through couple member reports, by observing couple members' behaviors during laboratory interactions, by observing responses to experimentally manipulated partner assistance provided during an individual laboratory task, and by following couples over a period of 6 months to examine independent goal striving as a function of prior assessments of dependency acceptance. Results provided converging evidence in support of the proposed hypothesis. Implications of the importance of close relationships for optimal individual functioning are discussed. PMID- 17279851 TI - What breaks a leader: the curvilinear relation between assertiveness and leadership. AB - The authors propose that individual differences in assertiveness play a critical role in perceptions about leaders. In contrast to prior work that focused on linear effects, the authors argue that individuals seen either as markedly low in assertiveness or as high in assertiveness are generally appraised as less effective leaders. Moreover, the authors claim that observers' perceptions of leaders as having too much or too little assertiveness are widespread. The authors linked the curvilinear effects of assertiveness to underlying tradeoffs between social outcomes (a high level of assertiveness worsens relationships) and instrumental outcomes (a low level of assertiveness limits goal achievement). In 3 studies, the authors used qualitative and quantitative approaches and found support for their account. The results suggest that assertiveness (and other constructs with nonlinear effects) might have been overlooked in research that has been focused on identifying what makes a leader rather than on identifying what breaks a leader. PMID- 17279852 TI - Self-control relies on glucose as a limited energy source: willpower is more than a metaphor. AB - The present work suggests that self-control relies on glucose as a limited energy source. Laboratory tests of self-control (i.e., the Stroop task, thought suppression, emotion regulation, attention control) and of social behaviors (i.e., helping behavior, coping with thoughts of death, stifling prejudice during an interracial interaction) showed that (a) acts of self-control reduced blood glucose levels, (b) low levels of blood glucose after an initial self-control task predicted poor performance on a subsequent self-control task, and (c) initial acts of self-control impaired performance on subsequent self-control tasks, but consuming a glucose drink eliminated these impairments. Self-control requires a certain amount of glucose to operate unimpaired. A single act of self control causes glucose to drop below optimal levels, thereby impairing subsequent attempts at self-control. PMID- 17279853 TI - Perceived cultural importance and actual self-importance of values in cultural identification. AB - Cross-cultural psychologists assume that core cultural values define to a large extent what a culture is. Typically, core values are identified through an actual self-importance approach, in which core values are those that members of the culture as a group strongly endorse. In this article, the authors propose a perceived cultural importance approach to identifying core values, in which core values are values that members of the culture as a group generally believe to be important in the culture. In 5 studies, the authors examine the utility of the perceived cultural importance approach. Results consistently showed that, compared with values of high actual self-importance, values of high perceived cultural importance play a more important role in cultural identification. These findings have important implications for conceptualizing and measuring cultures. PMID- 17279854 TI - Attachment and the experience and expression of emotions in romantic relationships: a developmental perspective. AB - In this longitudinal study, the authors tested a developmental hypothesis derived from attachment theory and recent empirical findings. Target participants were 78 individuals who have been studied intensively from infancy into their mid-20s. When targets were 20-23 years old, the authors tested the way in which interpersonal experiences at 3 pivotal points in each target's earlier social development--infancy/early childhood, early elementary school, and adolescence- predicted the pattern of positive versus negative emotions experienced with his or her romantic partner. A double-mediation model revealed that targets classified as securely attached at 12 months old were rated as more socially competent during early elementary school by their teachers. Targets' social competence, in turn, forecasted their having more secure relationships with close friends at age 16, which in turn predicted more positive daily emotional experiences in their adult romantic relationships (both self- and partner reported) and less negative affect in conflict resolution and collaborative tasks with their romantic partners (rated by observers). These results are discussed in terms of attachment theory and how antecedent life experiences may indirectly shape events in current relationships. PMID- 17279855 TI - Culturally competent nursing care: listening to the voices of Mexican-American women. AB - Mexican-Americans represent the fastest-growing minority population group in the United States. Gaining a cultural perspective of health care in the Mexican American population necessitates listening to the voices of women because they assume primary responsibility for maintaining family health. The Transcultural Assessment Model developed by Giger and Davidhizar (2004) provides the framework for this exploration of Mexican-American women's health care views. From this model the investigators developed an interview guide based on social organization and environmental control. Thematic analysis of interviews with six Mexican American women revealed the importance of the family, religion, and locus-of control in the health beliefs, attitudes, and lifestyle practices of this culture. Using the voices of Mexican-American women the investigators seek to promote an understanding of the culture as a guide for nursing care. The purpose of this article is to increase awareness of the Mexican-American cultural phenomena of social organization and environmental control which can guide the nurse to provide culturally competent care that meets the needs of Mexican American women and their families. PMID- 17279857 TI - A historical challenge: nurses and emergencies. AB - Nurses have been a part of disaster preparedness and response as long as nurses have existed. Although the early nurses who responded to emergencies during historic events may have been something other than the fully educated, licensed, certified, professional nurses as we know them today, their described role is consistent with a modern understanding of nursing: attention to the injured or ill individual; assuring provision of water, food, clean dressings, and bedding; providing relief from pain; and offering a human touch that says "I care." This article reviews the beginning of emergency nursing as a specialty, and the 21st century expectations about nursing during catastrophic events. Included are brief discussions of various nursing roles related to emergency care. PMID- 17279858 TI - Be safe, be prepared: emergency system for advance registration of volunteer health professionals in disaster response. AB - Following the September 11, 2001, incident in the United States (US) and subsequent natural disasters, the US, like other countries, has focused on improving its overall disaster response capabilities. One mechanism that is under development to improve the country's surge capacity, i.e., its ability to substantially increase the number of volunteer health care professionals available to respond during a disaster, is the Emergency System for Advance Registration of Volunteer Health Professionals (ESAR-VHP). Registries, like ESAR VHP, are significant tools for disaster planning and deployment. The goal of ESAR VHP is to create a state-based registry of volunteer health professionals, verify their credentials prior to a disaster, and provide opportunities for education and training in disaster response. Each of these steps is necessary in ensuring access to patient services during an emergency, while also providing for the safety of the volunteer health professional. This article speaks to the registered nurse as a volunteer acting within these types of registries. Specifically, it addresses the development of a personal and professional response plan, and registration programs that provide the preparation needed to enable a nurse responder to work effectively within a disaster response team and facilitate preregistration with one and only one registry. The legal implications of responding are also discussed. PMID- 17279859 TI - Preparing nurses internationally for emergency planning and response. AB - Competency-based education provides an international infrastructure for nurses to learn about emergency preparedness and response. The International Nursing Coalition for Mass Casualty Education (INCMCE) has developed competencies for all nurses, as well as online modules for meeting those competencies. In addition, other curriculum resources are available that range from face-to-face classes, web-based modules, and electronic journals, to complete pre-packaged materials. The author of this article describes competencies needed for emergency preparedness identified by Columbia University, Vanderbilt University, and the International Nursing Coalition for Mass Casualty Education, as well as various curriculum resources for emergency planning and response and also processes to prepare nurses for emergency responses. Examples of international "Best Practices" feature programs that provide examples of innovative educational strategies for preparing nurses for emergency response are presented. The author concludes that while curriculum resources are widely available, a better centralized clearinghouse could be made available for both faculty and students. PMID- 17279860 TI - A proposed model for military disaster nursing. AB - There is a dearth of literature examining models related to nursing disaster preparedness and response, particularly in military nursing. Several recent articles address lessons learned by nurses who worked through wars and disasters, and these experiences can be used as a basis for a proposed model of military disaster nursing. This article will (a) review the literature about disaster nursing, including general disaster responses by nurses, disaster responses in military nursing, and research about military nurses and disaster response, (b) describe the uniqueness of the military environment, and (c) propose a model for military disaster nursing that can be evaluated for future implementation. Research about individual nurse readiness for deployment during disasters is also incorporated into the proposed model. Future research is needed to test the model and examine its relevance to military, as well as civilian nursing for future disasters. PMID- 17279861 TI - Nutrition and disaster preparedness: focusing on vulnerability, building capacities. AB - Many disasters that occur throughout the world remain largely under-reported, frequently because they began a number of years ago, and have become "chronic" or "long term." Yet, in their vulnerability, the affected populations are no less deserving of humanitarian aid than those involved in the more acute, sudden disasters that make a major impact in the media. Aid providers need to direct their efforts at enabling populations to build their capacity and decrease their vulnerability, thus enhancing their preparedness for any future disaster. This article considers the importance of paying careful regard to the vulnerability, capacities, and disaster preparedness of people affected by these long-term disasters. Vulnerability, capacity, and disaster preparedness are examined specifically in the context of food shortages and malnutrition, with particular reference to the long-term disaster in the African country of Kenya. PMID- 17279862 TI - Historical, cultural, and contemporary influences on the status of women in nursing in Saudi Arabia. AB - Global nursing shortages have necessitated closer scrutiny of recruitment and retention initiatives of nurses both locally and internationally. For many decades the nursing workforce of Saudi Arabia has relied on international expatriates to be the backbone of the industry. In recent years however, Saudi women have been recruited into nursing preparation courses conducted at degree level. The many twists and turns of providing a local Saudi Arabian nursing workforce has paralleled Saudi's own history and this paper follows that journey. Our research has enabled us to provide some insights into nursing pre and post the enlightenment that accompanied the Prophet Mohammed's influence. We emphasize the influences of women leaders who emerged in Mohammed's time and bring lasting authority to the development of nursing in Saudi Arabia. The cultural issues that bind women in this society are explicated and related to recruitment and retention issues in nursing. Education matters, both past and present, are highlighted emphasizing the gains that nursing as a distinct occupation has made. Finally the paper concludes with a summation of contemporary achievements in Saudi Arabia moving nursing towards the much needed professional status and parity with other careers in health care. PMID- 17279863 TI - Metastability, nucleation, and noise-enhanced stabilization out of equilibrium. AB - We study metastability and nucleation in a kinetic two-dimensional Ising model that is driven out of equilibrium by a small random perturbation of the usual dynamics at temperature T. We show that, at a mesoscopic/cluster level, a nonequilibrium potential describes in a simple way metastable states and their decay. We thus predict noise-enhanced stability of the metastable phase and resonant propagation of domain walls at low T. This follows from the nonlinear interplay between thermal and nonequilibrium fluctuations, which induces reentrant behavior of the surface tension as a function of T. Our results, which are confirmed by Monte Carlo simulations, can be also understood in terms of a Langevin equation with competing additive and multiplicative noises. PMID- 17279864 TI - Sticky grains do not change the universality class of isotropic sandpiles. AB - We revisit the sandpile model with "sticky" grains introduced by Mohanty and Dhar [Phys. Rev. Lett. 89, 104303 (2002)] whose scaling properties were claimed to be generically in the universality class of directed percolation for both isotropic and directed models. While for directed models this conclusion is unquestionable, for isotropic models we present strong evidence that the asymptotic scaling in the self-organized regime (in which a stationary critical state exists in the limit of slow driving and vanishing dissipation rate) is, like other stochastic sandpiles, generically in the Manna universality class. This conclusion is drawn from extensive Monte Carlo simulations, and is strengthened by the analysis of the Langevin equations (proposed by the same authors to account for this problem), argued to converge upon coarse-graining to the well-established set of Langevin equations for the Manna class. PMID- 17279865 TI - Short-range stationary patterns and long-range disorder in an evolution equation for one-dimensional interfaces. AB - A local evolution equation for one-dimensional interfaces is derived in the context of erosion by ion beam sputtering. We present numerical simulations of this equation which show interrupted coarsening in which an ordered cell pattern develops with constant wavelength and amplitude at intermediate distances, while the profile is disordered and rough at larger distances. Moreover, for a wide range of parameters the lateral extent of ordered domains ranges up to tens of cells. We also provide analytical estimates for the stationary pattern wavelength and mean growth velocity. PMID- 17279866 TI - Extended law of corresponding states in short-range square wells: a potential energy landscape study. AB - We study the statistical properties of the potential energy landscape of a system of particles interacting via a very short-range square-well potential (of depth u0) as a function of the range of attraction Delta to provide thermodynamic insights of the Noro and Frenkel [M. G. Noro and D. Frenkel, J. Chem. Phys. 113, 2941 (2000)] scaling. We exactly evaluate the basin free energy and show that it can be separated into a vibrational (Delta dependent) and a floppy (Delta independent) component. We also show that the partition function is a function of Deltaebetauo, explaining the equivalence of the thermodynamics for systems characterized by the same second virial coefficient. An outcome of our approach is the possibility of counting the number of floppy modes (and their entropy). PMID- 17279867 TI - Relation between local diffusivity and local inherent structures in the Kob Andersen Lennard-Jones model. AB - We analyze one thousand independent equilibrium trajectories of a system of 155 Lennard-Jones particles to separate in a model-free approach the role of temperature and the role of the explored potential energy landscape basin depth in the particle dynamics. We show that the diffusion coefficient D can be estimated as a sum over contributions of the sampled basins, establishing a connection between thermodynamics and dynamics in the potential energy landscape framework. We provide evidence that the observed nonlinearity in the relation between local diffusion and basin depth is responsible for the peculiar dynamic behavior observed in supercooled states and provide an interpretation for the presence of dynamic heterogeneities. PMID- 17279868 TI - Structural and dynamical heterogeneity in a glass-forming liquid. AB - We use the "isoconfigurational ensemble" [Phys. Rev. Lett. 93, 135701 (2004)] to analyze both dynamical and structural properties in simulations of a glass forming molecular liquid. We show that spatially correlated clusters of low potential-energy molecules are observable on the time scale of structural relaxation, despite the absence of spatial correlations of potential energy in the instantaneous structure of the system. We find that these structural heterogeneities correlate with dynamical heterogeneities in the form of clusters of low molecular mobility. PMID- 17279869 TI - Anticonical anchoring and surface transitions in a nematic liquid crystal. AB - Recent works reported planar and conical azimuthally degenerated nematic anchorings. Here we predict an additional "anticonical" degenerated anchoring. Its energy presents two minima, parallel and perpendicular to the substrate plane, separated by a conical energy barrier. We realize this bistable anchoring on a grafted polymer brush and we observe temperature-driven transitions between the conical, planar, and anticonical degenerated anchorings. Under electric field we break the anticonical anchoring and switch between its bistable states. PMID- 17279870 TI - Bubble statistics and dynamics in double-stranded DNA. AB - The dynamical properties of double-stranded DNA are studied in the framework of the Peyrard-Bishop-Dauxois model using Langevin dynamics. Our simulations are analyzed in terms of two distribution functions describing localized separations ("bubbles") of the double strand. The result that the bubble distributions are more sharply peaked at the active sites than thermodynamically obtained distributions is ascribed to the fact that the bubble lifetimes affect the distributions. Certain base-pair sequences are found to promote long-lived bubbles, and we argue that this is a result of length scale competition between the nonlinearity and disorder present in the system. PMID- 17279872 TI - Violation of the des Cloizeaux relation for self-avoiding walks on Sierpinski square lattices. AB - The statistics of self-avoiding walks (SAWs) on deterministic fractal structures with infinite ramification, modeled by Sierpinski square lattices, is revisited in two and three dimensions using the reptation algorithm. The probability distribution function of the end-to-end distance of SAWs, consisting of up to 400 steps, is obtained and its scaling behavior at small distances is studied. The resulting scaling exponents are confronted with previous calculations for much shorter linear chains (20 to 30 steps) based on the exact enumeration (EE) technique. The present results coincide with the EE values in two dimensions, but differ slightly in three dimensions. A possible explanation for this discrepancy is discussed. Despite this, the violation of the so-called des Cloizeaux relation, a renormalization result that holds on regular lattices and on deterministic fractal structures with finite ramification, is confirmed numerically. PMID- 17279871 TI - Triangular Ising antiferromagnet: boundary conditions, ground state entropy, and vortices. AB - The ground state entropy density of the triangular Ising antiferromagnet is considered as a function of boundary conditions on domains for which the ground states do not admit a dimer covering. These domains admit a rich set of ground states that cannot be classified in the usual way in terms of nonintersecting strings. Various parametrized boundary conditions and domain shapes are identified that allow the ground state entropy density to be varied between zero and maximal degeneracy. The dependence of degeneracy on boundary spins and/or domain shape is interpreted in terms of strings that are not restricted to be nonintersecting. PMID- 17279873 TI - Thermodynamic instability of a confined gas. AB - The best possible cooling agent is a system with negative specific heat. If in thermal contact with a second system, any acquisition of energy due to a random fluctuation lowers its temperature, and the energy transfer in this direction is further enhanced. It continues until all the energy is extracted from the second system and their temperatures are at par. We exhibit these microcanonical features with a simple mechanical model of interacting classical gas particles in a specially confined domain and subjected to gravitation. As predicted, most of the gas particles are cooled and collect in the lowest part of the container, where the energy is carried away by a few remaining particles. PMID- 17279874 TI - Totally asymmetric exclusion process with long-range hopping. AB - Generalization of the one-dimensional totally asymmetric exclusion process (TASEP) with open boundary conditions in which particles are allowed to jump l sites ahead with the probability pl approximately 1l/sigma+1 is studied by Monte Carlo simulations and the domain-wall approach. For sigma>1 the standard TASEP phase diagram is recovered, but the density profiles display additional features when 1-infinity is directly related to the fluctuation exponent theta(d) [which governs the fluctuations DeltaE0(L) approximately Ltheta(d) of the ground-state energy E0 for polymers of length L] via the simple formula eta(d)=1/[1-theta(d)]. Throughout the paper, we comment on the similarities and differences with spin glasses. PMID- 17279880 TI - Flows on graphs with random capacities. AB - We investigate flows on graphs whose links have random capacities. For binary trees we derive the probability distribution for the maximal flow from the root to a leaf, and show that for infinite trees it vanishes beyond a certain threshold that depends on the distribution of capacities. We then examine the maximal total flux from the root to the leaves. Our methods generalize to simple graphs with loops, e.g., to hierarchical lattices and to complete graphs. PMID- 17279881 TI - Energy distribution and effective temperatures in a driven dissipative model. AB - We investigate nonequilibrium behavior of driven dissipative systems, using a model we recently presented [Phys. Rev. Lett., 93, 240601 (2004)]. We solve the non-Boltzmann steady state energy distribution and the temporal evolution to it, and find its high energy tail to behave exponentially. We demonstrate that various measures of effective temperatures generally differ. We discuss infinite hierarchies of effective temperatures defined from moments of the nonexponential energy distribution, and relate them to the "configurational temperature," measured directly from instantaneous particle locations without any kinetic information. We calculate the "granular temperature," characterizing the average energy in the system, two different "fluctuation temperatures," scaling fluctuation-dissipation relations, and the "entropic temperature," defined from differentiating the entropy with respect to energy. PMID- 17279882 TI - Fractional diffusion interpretation of simulated single-file systems in microporous materials. AB - The single-file diffusion of water in the straight channels of two different crystalline microporous aluminosilicates (zeolites bikitaite and Li-ABW) was studied by comparing the results of molecular dynamics computer simulations with the predictions of anomalous diffusion theory modeled by using fractional diffusion equations. At high coverage, the agreement is reasonably good, in particular for sufficiently large displacements and sufficiently long times. At low coverage, interesting phenomena appear in the simulation results, such as multimodal propagators, which could be interpreted on the basis of fractional Fokker-Planck equations. The results are discussed also in view of different theories that have been proposed to model the single-file diffusion process. PMID- 17279883 TI - High-temperature series expansions for the q-state Potts model on a hypercubic lattice and critical properties of percolation. AB - We present results for the high-temperature series expansions of the susceptibility and free energy of the q-state Potts model on a D-dimensional hypercubic lattice ZD for arbitrary values of q. The series are up to order 20 for dimension D1 limit of these series, we estimate the percolation threshold pc and critical exponent gamma for bond percolation in different dimensions. We also extend the 1/D expansion of the critical coupling for arbitrary values of q up to order D-9. PMID- 17279885 TI - Phenomenon of stochastic resonance caused by multiplicative asymmetric dichotomous noise. AB - The exact expression of the first moment and the signal-to-noise ratio (SNR) have been calculated for a linear system subject to an external periodic field as well as a multiplicative asymmetric dichotomous noise, by using the Shapiro-Loginov formula. It has been found that the amplitude of the output signal, and the SNR, respectively, exhibit two kinds of the phenomena of stochastic resonance: one is as the functions of the parameters of the asymmetric dichotomous noise, such as the noise strength D, and the parameter k describing the asymmetric degree of the dichotomous noise; the other is as the function of the parameter of the input signal, such as the input signal frequency omega. PMID- 17279884 TI - Current in a three-dimensional periodic tube with unbiased forces. AB - Transport of a Brownian particle moving along the axis of a three-dimensional asymmetric periodic tube is investigated in the presence of asymmetric unbiased forces. The reduction of the coordinates may involve not only the appearance of entropic barrier but also the effective diffusion coefficient. It is found that in the presence of entropic barrier, the asymmetry of the tube shape and the asymmetry of the unbiased forces are the two ways of inducing a net current. The current is a peaked function of temperature which indicates that the thermal noise may facilitate the transport even in the presence of entropic barrier. An optimized radius exists at the bottleneck at which the current takes its maximum value. Competition between the two opposite driving factors may induce current reversal. PMID- 17279886 TI - Nonperturbative renormalization group and momentum dependence of n-point functions. I. AB - We present an approximation scheme to solve the nonperturbative renormalization group equations and obtain the full momentum dependence of the n-point functions. It is based on an iterative procedure where, in a first step, an initial ansatz for the n-point functions is constructed by solving approximate flow equations derived from well motivated approximations. These approximations exploit the derivative expansion and the decoupling of high momentum modes. The method is applied to the O(N) model. In leading order, the self-energy is already accurate both in the perturbative and the scaling regimes. A stringent test is provided by the calculation of the shift DeltaTc in the transition temperature of the weakly repulsive Bose gas, a quantity which is particularly sensitive to all momentum scales. The leading order result is in agreement with lattice calculations, albeit with a theoretical uncertainty of about 25%. PMID- 17279887 TI - Nonperturbative renormalization group and momentum dependence of n-point functions. II. AB - In a companion paper [Blaizot, Phys. Rev. E 74, 051116 (2006)], we have presented an approximation scheme to solve the nonperturbative renormalization group equations that allows the calculation of the n-point functions for arbitrary values of the external momenta. The method was applied in its leading order to the calculation of the self-energy of the O(N) model in the critical regime. The purpose of the present paper is to extend this study to the next-to-leading order of the approximation scheme. This involves the calculation of the four-point function at leading order, where interesting features arise, related to the occurrence of exceptional configurations of momenta in the flow equations. These require a special treatment, inviting us to improve the straightforward iteration scheme that we originally proposed. The final result for the self-energy at next to-leading order exhibits a remarkable improvement as compared to the leading order calculation. This is demonstrated by the calculation of the shift DeltaTc, caused by weak interactions, in the temperature of Bose-Einstein condensation. This quantity depends on the self-energy at all momentum scales and can be used as a benchmark of the approximation. The improved next-to-leading order calculation of the self-energy presented in this paper leads to excellent agreement with lattice data and is within 4% of the exact large N result. PMID- 17279888 TI - Stochastic parametric amplification due to higher order correlations: a perturbative approach to non-Abelian effects in time ordering. AB - In this paper, we use quantum-mechanical formalism to describe the time evolution of a classical dynamical system with fluctuating parameters. By appropriate choice of "interaction picture representation," and the use of the Baker-Campbell Hausdorff formula in the chronological time ordered evolution, we have obtained analytical expressions for the Lyapunov exponent of the energy evolution of the dynamical system. Our approach proved to be very powerful in handling either stochastic or highly correlated processes. The approach lends itself to generalizations for use in a wide field of applications. PMID- 17279889 TI - Collisional statistics of a stochastic single file. AB - The anomalous diffusion of a single file of Brownian particles moving on a circle at a given temperature is characterized in terms of nearest-neighbor collisions. The time and the distance a particle diffuses (normally) between two successive collisions are computed numerically; their means, distributions, and correlation functions are determined for different values of the file parameters and reproduced analytically by means of simple phenomenological arguments. Most notably, the jump autocorrelation functions develop slow power-law tails. The ensuing impact representation of the single file dynamics suggests an alternate description of the single file diffusion as a geometrically constrained fluctuation mechanism. PMID- 17279890 TI - Real symmetric random matrices and replicas. AB - Various ensembles of random matrices with independent entries are analyzed by the replica formalism in the large- N limit. A result on the Laplacian random matrix with Wigner-rescaling is generalized to arbitrary probability distribution. PMID- 17279891 TI - Master equation and two heat reservoirs. AB - A simple spin-flip process is analyzed under the presence of two heat reservoirs. While one flip process is triggered by a bath at temperature T, the inverse process is activated by a bath at a different temperature T'. The situation can be described by using a master equation approach in a second quantized Hamiltonian formulation. The stationary solution leads to a generalized Fermi Dirac distribution with an effective temperature Te. Likewise the relaxation time is given in terms of Te. Introducing a spin representation we perform a Landau expansion for the averaged spin as order parameter and consequently, a free energy functional can be derived. Owing to the two reservoirs the model is invariant with respect to a simultaneous change sigma<-->-sigma and T<-->T'. This symmetry generates a third order term in the free energy which gives rise a dynamically induced first order transition. PMID- 17279892 TI - Extracting the scaling exponents of a self-affine, non-Gaussian process from a finite-length time series. AB - We address the generic problem of extracting the scaling exponents of a stationary, self-affine process realized by a time series of finite length, where information about the process is not known a priori. Estimating the scaling exponents relies upon estimating the moments, or more typically structure functions, of the probability density of the differenced time series. If the probability density is heavy tailed, outliers strongly influence the scaling behavior of the moments. From an operational point of view, we wish to recover the scaling exponents of the underlying process by excluding a minimal population of these outliers. We test these ideas on a synthetically generated symmetric alpha -stable Levy process and show that the Levy exponent is recovered in up to the 6th order moment after only approximately 0.1-0.5% of the data are excluded. The scaling properties of the excluded outliers can then be tested to provide additional information about the system. PMID- 17279893 TI - Short-time dynamics of percolation observables. AB - We consider the critical short-time evolution of magnetic and droplet-percolation order parameters for the Ising model in two and three dimensions, through Monte Carlo simulations with the (local) heat-bath method. We find qualitatively different dynamic behaviors for the two types of order parameters. More precisely, we find that the percolation order parameter does not have a power-law behavior as encountered for the magnetization, but develops a scale (related to the relaxation time to equilibrium) in the Monte Carlo time. We argue that this difference is due to the difficulty in forming large clusters at the early stages of the evolution. Our results show that, although the descriptions in terms of magnetic and percolation order parameters may be equivalent in the equilibrium regime, greater care must be taken to interpret percolation observables at short times. In particular, this concerns the attempts to describe the dynamics of the deconfinement phase transition in QCD using cluster observables. PMID- 17279894 TI - Power-law random walks. AB - In this paper, random walks with independent steps distributed according to a Q power-law probability distribution function with Q=1/(1-q) are studied. In the case q>1, we show that (i) a stochastic representation of the location of the walk after n steps can be explicitly given (for both finite and infinite variance) and (ii) a clear connection with the superstatistics framework can be established (including the anomalous diffusion case). In the case q<1, we prove that this random walk can be considered as the projection of an isotropic random walk, i.e., a random walk with fixed length steps and uniformly distributed directions. These results provide a natural extension of (i) the usual Gaussian framework and (ii) the infinite-covariance case of the superstatistics treatments. PMID- 17279895 TI - Mass dependence of shear viscosity in a binary fluid mixture: mode-coupling theory. AB - An expression for the shear viscosity of a binary fluid mixture is derived using mode-coupling theory in order to study the mass dependence. The calculated results on shear viscosity for a binary isotopic Lennard-Jones fluid mixture show good agreement with results from molecular dynamics simulation carried out over a wide range of mass ratio at different composition. Also proposed is a new generalized Stokes-Einstein relation connecting the individual diffusivities to shear viscosity. PMID- 17279896 TI - Power-law and exponential segregation in two-dimensional silos of granular mixtures. AB - When a binary mixture of granular materials, differing in shape or size, is poured into a quasi-two-dimensional silo, segregation of the mixture is observed. Depending on the size ratio d2/d1 of the species, the mixture segregates completely or partially into the pure species. To study the partial-segregation effect we propose a theoretical model based on the work of Boutreux and de Gennes [J. Phys. I 6, 1295 (1996)] but we introduce more realistic collision functions. To compare the partial- and complete-segregation effects, we also discuss calculations for the complete-segregation model proposed by Makse [Phys. Rev. E 56, 7008 (1997)]. Our experiments confirm the analytical solutions for both types of segregation. We find that the transition from complete segregation to partial segregation appears as the size ratio of the species is decreased below a critical value, which is found to be d2/d1 approximately 1.4 for our system. Our experimental and analytical studies predict the regime for applicability of both partial- and complete-segregation models in terms of the size ratio of the species and the respective model parameters. PMID- 17279897 TI - Velocity correlations in dense gravity-driven granular chute flow. AB - We report numerical results for velocity correlations in dense, gravity-driven granular flow down an inclined plane. For the grains on the surface layer, our results are consistent with experimental measurements reported by Pouliquen. We show that the correlation structure within planes parallel to the surface persists in the bulk. The two-point velocity correlation function exhibits exponential decay for small to intermediate values of the separation between spheres. The correlation lengths identified by exponential fits to the data show nontrivial dependence on the averaging time Deltat used to determine grain velocities. We discuss the correlation length dependence on averaging time, incline angle, pile height, depth of the layer, system size, and grain stiffness and relate the results to other length scales associated with the rheology of the system. We find that correlation lengths are typically quite small, of the order of a particle diameter, and increase approximately logarithmically with a minimum pile height for which flow is possible, hstop, contrary to the theoretical expectation of a proportional relationship between the two length scales. PMID- 17279898 TI - Force heterogeneities in particle assemblies: from order to disorder. AB - The effect of increasing structural disorder on the distribution of contact forces P(f) inside three dimensional particle assemblies is systematically studied using computer simulations of model granular packings. Starting from a face-centered-cubic array, where all contact forces are identical, an increasing number of defects is introduced into the assembly, after which the system is then allowed to relax into a different mechanically stable state. Three distinct protocols for imposing disorder are compared. A quantitative measure of the disorder is obtained from distributions of the coordination number and three particle contact angle. The distribution of normal contact forces show dramatic qualitative changes with increasing disorder. In the regime where the disorder is relatively weak, the pressure and the lowest normal mode frequency scale approximately linearly in the coordination number, with distance from the crystalline state. These results for P(f) are discussed in the context of jamming phenomena in glassy and granular materials. PMID- 17279899 TI - Clustering instability in a freely falling granular jet. AB - This paper investigates a clustering instability of a freely falling granular jet composed of 100 microm glass spheres. The granular flow out of a circular nozzle starts out spatially uniform and then, further downstream, breaks up into well defined clusters. An optical method is used that measures inhomogeneities in the flow in order to quantify the growth of the clusters. The role of air is investigated in this phenomenon by changing the ambient air pressure down to 1/5000th atm. Clustering is observed down to the lowest pressure and the presence of air leads to larger clusters but does not initiate the cluster formation. The analysis shows that the cluster size is set by fluctuations on the order of the size of the particles at the nozzle. PMID- 17279900 TI - Radial granular segregation under chaotic flow in two-dimensional tumblers. AB - An initially well mixed granular material composed of two distinct subclasses of particles, small and large or light and heavy, segregates radially into stable lobed patterns when rotated in various quasi-two-dimensional, regular polygonal tumblers. The patterns are highly sensitive to the time-periodic flow, which in turn depends critically on the fill fraction and container shape. Simulations of a simple model reproduce the segregation patterns observed in experiment. Kolmogorov-Arnol'd-Moser (KAM) regions in Poincare plots of the velocity field used to model the flow attract smaller (denser) particles and their spatial symmetries mirror those of the segregation patterns, suggesting that competition between the driving forces for radial segregation (percolation and buoyancy) and those for chaotic mixing plays a key role. PMID- 17279901 TI - Phases of granular segregation in a binary mixture. AB - We present results from an extensive experimental investigation into granular segregation of a shallow binary mixture in which particles are driven by frictional interactions with the surface of a vibrating horizontal tray. Three distinct phases of the mixture are established viz. binary gas (unsegregated), segregation liquid, and segregation crystal. Their ranges of existence are mapped out as a function of the system's primary control parameters using a number of measures based on Voronoi tessellation. We study the associated transitions and show that segregation can be suppressed as the total filling fraction of the granular layer, C, is decreased below a critical value, Cc, or if the dimensionless acceleration of the driving, gamma, is increased above a value gammac. PMID- 17279902 TI - Failure and strengthening of granular slopes under horizontal vibration. AB - We present experimental measurements of a granular slope under horizontal vibration. We use optical particle tracking to measure the motion of surface beads as the slope fails. We find that for all but the largest inclination angles, initial bead motion leads to strengthening rather than an avalanche. The initial motion of the beads is usually intermittent and evolves differently for different preparations, slope angles, and rates of increase in the vibration amplitude. When a specific criterion is chosen to define failure, the Coulomb friction model adequately describes the average acceleration required to produce failure, as long as slope preparation and experimental protocol are constant. However, the observed intermittent motion and rate dependence indicate that strengthening microrearrangements are important features that affect failure of slopes under external perturbations. PMID- 17279903 TI - Generalized hydrodynamics of a dilute suspension of finite-sized particles: dynamic viscosity. AB - We present a mesoscopic hydrodynamic description of the dynamics of colloidal suspensions. We consider the system as a gas of Brownian particles suspended in a Newtonian heat bath subjected to stationary nonequilibrium conditions imposed by a velocity field. By means of a generalized Fokker-Planck equation, we obtain a set of coupled differential equations for the local diffusion current and the evolution of the total stress tensor. We find that the dynamic shear viscosity of the system contains contributions arising from the finite size of the particles. PMID- 17279904 TI - Equation of state of colloids coated by polyelectrolyte multilayers. AB - We propose an adaptation of the osmotic stress technique for determining equations of state of colloids covered by polymer films. We describe here the case of silica particles covered by 6 or 7 layers of polyelectrolyte multilayers. The establishment of a pressure-distance curve allows the interpretation of colloidal interactions over more than four orders of magnitude in pressure. This large range allows a clear separation between three distinct regimes: layer compression, brush extension and at very low pressures a regime of weak repulsion. The physical origins of the regimes are discussed and described by models of colloidal interactions. PMID- 17279905 TI - Viscous froth lens. AB - Microscale models of foam structure traditionally incorporate a balance between bubble pressures and surface tension forces associated with curvature of bubble films. In particular, models for flowing foam microrheology have assumed this balance is maintained under the action of some externally imposed motion. Recently, however, a dynamic model for foam structure has been proposed, the viscous froth model, which balances the net effect of bubble pressures and surface tension to viscous dissipation forces: this permits the description of fast-flowing foam. This contribution examines the behavior of the viscous froth model when applied to a paradigm problem with a particularly simple geometry: namely, a two-dimensional bubble "lens." The lens consists of a channel partly filled by a bubble (known as the "lens bubble") which contacts one channel wall. An additional film (known as the "spanning film") connects to this bubble spanning the distance from the opposite channel wall. This simple structure can be set in motion and deformed out of equilibrium by applying a pressure across the spanning film: a rich dynamical behavior results. Solutions for the lens structure steadily propagating along the channel can be computed by the viscous froth model. Perturbation solutions are obtained in the limit of a lens structure with weak applied pressures, while numerical solutions are available for higher pressures. These steadily propagating solutions suggest that small lenses move faster than large ones, while both small and large lens bubbles are quite resistant to deformation, at least for weak applied back pressures. As the applied back pressure grows, the structure with the small lens bubble remains relatively stiff, while that with the large lens bubble becomes much more compliant. However, with even further increases in the applied back pressure, a critical pressure appears to exist for which the steady-state structure loses stability and unsteady-state numerical simulations show it breaks up by route of a topological transformation. PMID- 17279906 TI - Particle migration induced by confinement of colloidal suspensions along the gravitational direction. AB - We confine charged spheres in cells with the smallest dimension along the direction of gravity g. The particles are density mismatched with the surrounding medium and sediment along g with typical Peclet numbers of Pe approximately 10( 3). After a certain time, we find that the number of particles N increases near both upper and lower plates until a characteristic time tau is reached; above this time N plateaus. We attribute the observed phenomenology to collective particle motions driven by gravity and mediated by hydrodynamic interactions; these could yield formation of swirls made of particles with correlated velocities that could eventually drive the particles towards the upper plate. The characteristic time for these migrations scales with plate-to-plate separation Lz as tau approximately Lz1.2, exactly as the characteristic decay time of velocity fluctuations in sedimentation processes [S. Y. Tee, Phys. Rev. Lett. 89, 054501 (2002)], despite that in these experiments the smallest cell dimension is perpendicular to g and 7T*. Particular attention is focused close to T*, where the interplay between jamming and percolation restricts fluctuations, forcing exponents seemingly different from the standard percolation universality class. By analogy with a thermal transition, we study the onset of percolation using the temperature T as a control parameter. We propose thermal scaling Ansatze to analyze the behavior of the percolation threshold and its thermally induced fluctuations. Also, the fractal dimension of the percolating cluster is determined. Based on these measurements and the excellent data collapse, we conclude that the universality class of standard percolation is preserved for all temperatures. PMID- 17279919 TI - Feasibility of large free-standing liquid films in space. AB - We consider the feasibility of large-scale free-standing thin liquid film experiment in the space environment as a new realization to study two-dimensional hydrodynamics. We identify material and environmental criteria necessary to avoid freezing, evaporation, chemical degradation, and spontaneous collapse of the film. These criteria pose no obstacles to achieving films of kilometer scale and lifetime of many months, with attainable Reynolds number up to 10(7). However, impacts from meteoroids pose a serious threat to the film, and require substantial shielding or unproven self-healing properties in the film. Current theoretical and experimental studies of two-dimensional turbulence are briefly reviewed. We also describe a specific candidate liquid for the film. PMID- 17279920 TI - Corresponding states of order parameter in nematic liquid crystals. AB - In this work, experimental data points from which the profile of the order parameter of nematic liquid crystals can be obtained, mainly magnetic susceptibility anisotropy and dielectric anisotropy, will be used to show that when rescaled they coalesce along a common line that extends from the nematic isotropic phase transition region, until the nematic-crystalline phase transition region. A large set of experimental data of a diversity of nematic compounds that share the presence of a nematic-isotropic and a nematic-crystalline phase transition, without another phase within, has been collected from the liquid crystals literature. Taking for each of them the temperatures of these two phase transitions as fixed points, a common temperature scale has been constructed and, in this scale, the value of each physical quantity has been uniformly fixed at the nematic-crystalline phase transition temperature. This procedure has revealed the existence of a law of corresponding states that covers the entire nematic phase. As the values assumed by these physical quantities can be used to measure the macroscopic order parameter, the use of this temperature scale suggests that it presents a common behavior that covers the entire nematic phase. PMID- 17279921 TI - Proton NMR relaxation of the dipolar quasi-invariants of nematic methyl deuterated para-azoxyanisole within the high-temperature Redfield relaxation theory. AB - The high-temperature Redfield spin-lattice relaxation theory is used for calculating the relaxation times of the different dipolar quasi-invariants in an eight-spin system which represents methyl deuterated para-azoxyanisole (PAAd6) in the nematic phase. According to previous experiments, this system can be considered as composed of weakly coupled pairs of strongly interacting spins, the ortho protons of the aromatic rings, thus, it possesses four quasi-invariants of the motion: Zeeman, dipolar intrapair and interpair, and singlet orders. We write the set of coupled differential equations which describe the relaxation of the generalized inverse spin temperatures of the four quasi-invariants. The relaxation constants are then calculated in terms of experimental two-spin spectral densities of the lattice motions. The relation between the multispin and the two-spin spectral densities is also deduced. Calculation shows that the Zeeman and singlet quasi-invariants are uncoupled from the dipolar ones, and that the relaxation time of the singlet order is much longer than those of the Zeeman and dipolar orders. The calculated cross relaxation rate between the dipolar orders through the lattice is small enough to be observable in the experiment. We also show that the nonsecular term associated with the collective motions dominates relaxation of the intrapair and interpair energies in PAAd6, while the local motions do not play a significant role, in qualitative agreement with the reported experimental behavior. The dipolar relaxation times predicted by the theory are significantly larger than the experimental ones, the difference being even more pronounced for the interpair quasi-invariant. We show that the discrepancy cannot be overcome neither by resorting to a realistic model for the spin system nor considering the various possible cross-relaxation pathways among the quasi-invariants. This feature points out the high- temperature approximation as a source of the discrepancy. We discuss the effect that slow and ultraslow molecular modes could have on the relaxation of the dipolar order. PMID- 17279922 TI - Frustrated smectic layer structures in bent-shaped dimer liquid crystals studied by x-ray microbeam diffraction. AB - The layer structures in bent-shaped liquid crystal dimers mOAM5AMOm (m=6-16) have been investigated by x-ray microbeam diffraction. These liquid crystal molecules have two rodlike mesogens connected with an odd-numbered alkylene spacer and form a bent shape. In these compounds it is found that the structure changes from the single (m=6) to frustrated-layer structures (m=8, 10, and 12) and switchable frustrated-layer structures (m=14 and 16) with increasing terminal chain length. An anticlinic antiferroelectric structure is suggested in the compound with m=16, based on the different electric-field-induced reorientation behavior from those in the other dimers. PMID- 17279924 TI - Surface effects on the relaxation dynamics of hexatic-B liquid-crystal films. AB - Based in a linearized hydrodynamic model, we study the relaxation dynamics of hexatic-B liquid-crystal films in two distinct cases. First, we investigate the hexatic order relaxing through a purely diffusive process for which the particles velocity field is assumed to be negligible. In this case, the asymptotic relaxation of deformations in the hexatic order presents a pronounced dependence on the boundary conditions. We found that a surface tilted order is enough to drive the slowest relaxation mode from an acoustic to an optic character. Second, we study the viscous case which is characterized by the coupling between the particles velocity field and the bond orientational order. In this case, underdamped modes with oscillatory-exponential relaxation are obtained on a narrow range of wave vectors. Further, the viscous relaxation of surface and inner layers deformations display distinct scaling behaviors under a surface tilted order. PMID- 17279923 TI - Cholesteric liquid crystals with a helical pitch gradient: spatial distribution of the concentration of chiral groups by Raman mapping in relation with the optical response and the microstructure. AB - Cholesteric liquid crystals (CLC) selectively reflect light when the helical pitch is of the order of the wavelength of the incident beam propagating along the helix axis. The wavelength bandwidth, related to the optical anisotropy, is typically limited to a few tens of nanometers in the visible part of the spectrum, which is insufficient for applications such as white-or-black polarizer free reflective displays and smart windows for the control of the solar light and heat. A way to make cholesteric films reflecting in a broad wavelength band consists in associating various cholesteric pitches in the same film. In this work, it is shown how a study by confocal micro Raman spectrometry mapping makes it possible to have access to information accounting for the local organization of CLCs in the case of graded pitch materials. These investigations will be correlated to the optical response and the transverse microstructure of the CLC material as investigated by transmission electron microscopy. An accurate analysis of the vibrational behavior evolution of the C==O can be correlated to the evolution of the populations of the chiral and achiral groups in the case of the interdiffusion of two CLC substances with various stoechiometries. Besides an easy measurement of the Raman spectrum gives the opportunity to quantify the relative ratio of the mesogenic species and thus to go up by a simple way to the pitch of the helical structure. PMID- 17279925 TI - Experimental demonstration, using polarized Raman and infrared spectroscopy, that both conventional and de Vries smectic-A phases may exist in smectic liquid crystals with a first-order A-C* transition. AB - Two models exist for the orientational distribution of the long molecular axes in smectic-A liquid crystals: the conventional unimodal distribution and the "cone shaped" de Vries distribution. The de Vries hypothesis provides a plausible picture of how, at a molecular level, a first-order Sm-A to Sm-C* transition may occur, especially if there is little or no concomitant shrinkage of the layer spacing. This work investigates two materials with such transitions: C7 and TSiKN65. The azimuthal distribution of in-layer directors is probed using IR and polarized Raman spectroscopy, which allows us to obtain orientational order parameters. In C7, we observe a discontinuous change in the order parameter, the magnitude of which is small compared with the corresponding change in the in layer director tilt angle Theta . Assuming that the smectic-A liquid crystal is of the de Vries type, we calculate the Theta required to reproduce the apparent order parameter app, obtained from IR, by using the true order parameter , obtained from polarized Raman scattering. The results indicate that, for C7, the tilt angle so calculated is much smaller than that in the Sm-C* angle and hence de Vries behavior may not be the appropriate explanation in this case. Conversely, we find that TSiKN65 shows a different behavior to C7, which can be explained in terms of the de Vries concept. Thus, we conclude that either type of distribution may exist in Sm-A phases which undergo a first-order transition to the Sm-C* phase. We also discuss the changes in the smectic layer spacing and the orientational order parameters across the Sm-A-Sm-C* phase transition, together with changes in birefringence with applied electric field. PMID- 17279926 TI - Nematic-isotropic transition with quenched disorder. AB - Nematic elastomers do not show the discontinuous, first-order, phase transition that the Landau-De Gennes mean field theory predicts for a quadrupolar ordering in three dimensions. We attribute this behavior to the presence of network crosslinks, which act as sources of quenched orientational disorder. We show that the addition of weak random anisotropy results in a singular renormalization of the Landau-De Gennes expression, adding an energy term proportional to the inverse quartic power of order parameter Q. This reduces the first-order discontinuity in Q. For sufficiently high disorder strength the jump disappears altogether and the phase transition becomes continuous, in some ways resembling the supercritical transitions in external field. PMID- 17279927 TI - Dielectric study on the shear-induced structural changes in the nematic and the smectic-A phases of 4-n-octyl-4'-cyanobiphenyl (8CB). AB - Dielectric measurements under steady shear flow are made to clarify the shear induced structural changes in the nematic (N) and the smectic-A (SA) phases of 4 n-octyl-4'-cyanobiphenyl (8CB). In the N phase, the temperature dependence of the dielectric permittivity shows a characteristic behavior, which can be consistently interpreted based on the shear-induced structures suggested by x-ray scattering; flow alignment of the director and some dynamical structures characterized by different precessional motions of the director. For the shear induced structural change in the SA phase, it is suggested that undulation instability would play an important role. PMID- 17279928 TI - Soft elasticity in biaxial smectic and smectic-C elastomers. AB - Ideal (monodomain) smectic-A elastomers cross-linked in the smectic-A phase are simply uniaxial rubbers, provided deformations are small. From these materials smectic-C elastomers are produced by a cooling through the smectic-A to smectic-C phase transition. At least in principle, biaxial smectic elastomers could also be produced via cooling from the smectic-A to a biaxial smectic phase. These phase transitions, respectively, from Dinfinityh to C2h and from Dinfinityh to D2h symmetry, spontaneously break the rotational symmetry in the smectic planes. We study the above transitions and the elasticity of the smectic-C and biaxial phases in three different but related models: Landau-like phenomenological models as functions of the Cauchy-Saint-Laurent strain tensor for both the biaxial and the smectic-C phases and a detailed model, including contributions from the elastic network, smectic layer compression, and smectic-C tilt for the smectic-C phase as a function of both strain and the c-director. We show that the emergent phases exhibit soft elasticity characterized by the vanishing of certain elastic moduli. We analyze in some detail the role of spontaneous symmetry breaking as the origin of soft elasticity and we discuss different manifestations of softness like the absence of restoring forces under certain shears and extensional strains. PMID- 17279929 TI - Optical and confocal microscopy observations of screw dislocations in smectic-A liquid crystals. AB - We present experimental evidence of the presence of isolated screw dislocations in smectic-A liquid crystals observed by polarizing microscopy. In a wedge-shaped homeotropic cell, the edge and screw dislocations interaction gives rise to a strong-enough optical contrast and makes visible their mutual intersections at temperatures close to the smectic-A to smectic-C phase transition temperature. The nature of the defects is confirmed by confocal microscopy observations. At large scale we observe a forest of screw dislocations, perpendicular to the smectic layers, across the thickness of the cell (end-on configuration). Their density varies between 10(9) and 10(12) m-2. In situ observations of dislocations under stress, in the optical microscope, provide quantitative information about the screw-edge dislocation interactions. The latter interaction is calculated in the unharmonic approximation and it gives rise to an observed yield stress. PMID- 17279930 TI - Secondary structures in long compact polymers. AB - Compact polymers are self-avoiding random walks that visit every site on a lattice. This polymer model is used widely for studying statistical problems inspired by protein folding. One difficulty with using compact polymers to perform numerical calculations is generating a sufficiently large number of randomly sampled configurations. We present a Monte Carlo algorithm that uniformly samples compact polymer configurations in an efficient manner, allowing investigations of chains much longer than previously studied. Chain configurations generated by the algorithm are used to compute statistics of secondary structures in compact polymers. We determine the fraction of monomers participating in secondary structures, and show that it is self-averaging in the long-chain limit and strictly less than 1. Comparison with results for lattice models of open polymer chains shows that compact chains are significantly more likely to form secondary structure. PMID- 17279931 TI - Effects of solvent immiscibility on the phase behavior and microstructural length scales of a diblock copolymer in the presence of two solvents. AB - We employ self-consistent mean-field theory to study the phase behavior and the microstructural sizes of AB diblock copolymers in the presence of a neutral solvent S1 and a slightly B-selective solvent S2. In particular, the effects of copolymer volume fraction phiC, the solvent ratio, and the immiscibility parameter between two solvents chiS1S2, are examined. We find that increasing chiS1S2 not only enlarges the ordered microphase region in the concentrated solutions, but also induces a less concentrated homogeneous solution to form an ordered structure and even undergo a macrophase separation. This is due to the fact that increasing chiS1S2 enhances the preferentially of S1 for A and S2 for B and, thereafter, the effective segregation between A and B. Hence, we observe that the structural length results obtained by varying chiS1S2 resemble a consequence of varying the solvent selectivity in the diblock copolymer solutions when only one solvent is added. For example, when chiS1S2 is small, the domain spacing decreases with decreasing phiC while at larger values of chiS1S2, it first shows a decreasing trend and then an increasing behavior with decreasing phiC. PMID- 17279932 TI - RNA-like polymer model: exact calculation on the Bethe lattice. AB - We consider a lattice polymer model (random walk), in which the walk is allowed to visit lattice bonds at most twice. Such a model might have some relevance to describe statistical properties of RNA molecules. In order to mimic base pairing, we assign an attractive energy term to each doubly visited bond, and a further contribution to each pair of consecutive doubly visited bonds. The latter term is expected to mimic the stacking effect, whereas no effect of sequence, that is, of chemical specificity, is taken into account. The phase diagram is worked out exactly on a Bethe lattice, in a grand-canonical formulation. In the single molecule limit, the system undergoes two different phase transitions upon decreasing temperature: a Theta-like collapse from a swollen "coil" state to a "molten" state, with a low fraction of doubly visited bonds, and subsequently to a "paired" state, with empty or doubly visited bonds only. The stacking effect drives the latter transition from second to first order. PMID- 17279933 TI - Thermodynamics of organisms in the context of dynamic energy budget theory. AB - We carry out a thermodynamic analysis to an organism. It is applicable to any type of organism because (1) it is based on a thermodynamic formalism applicable to all open thermodynamic systems and (2) uses a general model to describe the internal structure of the organism--the dynamic energy budget (DEB) model. Our results on the thermodynamics of DEB organisms are the following. (1) Thermodynamic constraints for the following types of organisms: (a) aerobic and exothermic, (b) anaerobic and exothermic, and (c) anaerobic and endothermic; showing that anaerobic organisms have a higher thermodynamic flexibility. (2) A way to compute the changes in the enthalpy and in the entropy of living biomass that accompany changes in growth rate solving the problem of evaluating the thermodynamic properties of biomass as a function of the amount of reserves. (3) Two expressions for Thornton's coefficient that explain its experimental variability and theoretically underpin its use in metabolic studies. (4) A mechanism that organisms in non-steady-state use to rid themselves of internal entropy production: "dilution of entropy production by growth." To demonstrate the practical applicability of DEB theory to quantify thermodynamic changes in organisms we use published data on Klebsiella aerogenes growing aerobically in a continuous culture. We obtain different values for molar entropies of the reserve and the structure of Klebsiella aerogenes proving that the reserve density concept of DEB theory is essential in discussions concerning (a) the relationship between organization and entropy and (b) the mechanism of storing entropy in new biomass. Additionally, our results suggest that the entropy of dead biomass is significantly different from the entropy of living biomass. PMID- 17279934 TI - Complex movements of motor protein relay helices during the power stroke. AB - We use the Toda soliton formalism to propose a possible complex movement of alpha helices with a very important role in energy transduction during the power stroke of motor proteins. We find that this approach has advantages in comparison with the Davydov soliton model and its variants. We estimated the model's parameters and calculated corresponding properties of the predicted solitary waves including propagation velocities and energies. The energies are found to be within the expected range. PMID- 17279935 TI - Subgraph ensembles and motif discovery using an alternative heuristic for graph isomorphism. AB - A heuristic based on vertex invariants is developed to rapidly distinguish nonisomorphic graphs to a desired level of accuracy. The method is applied to sample subgraphs from an Escherichia coli protein interaction network, and as a probe for discovery of extended motifs. The network's structure is described using statistical properties of its N-node subgraphs for N1, which may lead to the so-called Eve effect. We characterize these anomalies and their associated demographic distributions. We argue that this anomaly is similar in nature to the well known first-passage problem. PMID- 17279948 TI - Iridescence in the neck feathers of domestic pigeons. AB - We conducted structural characterizations, reflection measurements, and theoretical simulations on the iridescent green and purple neck feathers of domestic pigeons (Columba livia domestica). We found that both green and purple barbules are composed of an outer keratin cortex layer surrounding a medullary layer. The thickness of the keratin cortex layer shows a distinct difference between green and purple barbules. Green barbules vary colors from green to purple with the observing angle changed from normal to oblique, while purple barbules from purple to green in an opposite way. Both the experimental and theoretical results suggest that structural colors in green and purple neck feathers should originate from the interference in the top keratin cortex layer, while the structure beyond acts as a poor mirror. PMID- 17279949 TI - Finite-size domains in membranes with active two-state inclusions. AB - The distribution of inclusion-rich domains in membranes with active two-state inclusions is studied by simulations. Our study shows that typical size of inclusion-rich domains (L) can be controlled by inclusion activities in several ways. When there is effective attraction between state-1 inclusions, we find: (i) Small domains with only several inclusions are observed for inclusions with time scales (approximately 10(-3)s) and interaction energy [approximately Omicron(kBT)] comparable to motor proteins. (ii) L scales as 13 power of the lifetime of state-1 for a wide range of parameters. (iii) L shows a switch-like dependence on state-2 lifetime k12(-1). That is, L depends weakly on k12 when k12k12*, the crossover k12* occurs when the diffusion length of a typical state-2 inclusion within its lifetime is comparable to L. (iv) Inclusion-curvature coupling provides another length scale that competes with the effects of transition rates. PMID- 17279950 TI - Designability and cooperative folding in a four-letter hydrophobic-polar model of proteins. AB - The two-letter hydrophobic-polar (HP) model of Lau and Dill [Macromolecules 22, 3986 (1989)] has been widely used in theoretical studies of protein folding due to its conceptual and computational simplicity. Despite its success in elucidating various aspects of the sequence-structure relationship, thermodynamic behavior of the model is not in agreement with a sharp two-state folding transition of many single-domain proteins. To gain a better understanding of this discrepancy, we consider an extension of the HP model by including an "antiferromagnetic" (AF) interaction in the contact potential that favors amino acid residues with complementary attributes. With an enlarged four-letter alphabet, the density of states on the low energy side can be significantly decreased. Computational studies of the four-letter HP model are performed on 36 mer sequences on a square lattice. It is found that the designability of folded structures in the extended model exhibits strong correlation with that of the two letter HP model, while the AF interaction alone selects a very different class of structures that resembles the Greek key motif for beta sheets. A procedure is introduced to select sequences which have the largest energy gap to the native state. Based on density of states and specific heat calculations in the full configuration space, we show that the optimized sequence is able to fold nearly as cooperatively as a corresponding Go model. PMID- 17279951 TI - Controlling species richness in spin-glass model ecosystems. AB - Within the framework of the random replicator model of ecosystems, we use equilibrium statistical mechanics tools to study the effect of manipulating the ecosystem so as to guarantee that a fixed fraction of the surviving species at equilibrium display a predefined set of characters (e.g., characters of economic value). Provided that the intraspecies competition is not too weak, we find that the consequence of such intervention on the ecosystem composition is a significant increase on the number of species that become extinct, and so the impoverishment of the ecosystem. PMID- 17279952 TI - White-noise susceptibility and critical slowing in neurons near spiking threshold. AB - We present mathematical and simulation analyses of the below-threshold noisy response of two biophysically motivated models for excitable membrane due to H. R. Wilson: a squid axon ("resonator") and a human cortical neuron ("integrator"). When stimulated with a low-intensity white noise superimposed on a dc control current, both membrane types generate voltage fluctuations that exhibit critical slowing down--that is, the voltage responsiveness to noisy input currents grows in amplitude while slowing in frequency--as the membrane approaches spiking threshold from below. We define threshold unambiguously as that dc current that renders a zero real eigenvalue for the Jacobian matrix for the integrator neuron, and, for the resonator neuron, as the dc current that gives a complex eigenvalue pair whose real part is zero. Using a linear Ornstein-Uhlenbeck analysis, we give exact small-noise expressions for the variance, power spectrum, and correlation function of the voltage fluctuations, and we derive the scaling laws for the divergence of susceptibility and correlation times for approach to threshold. We compare these predictions with numerical simulations of the nonlinear stochastic equations, and demonstrate that, provided the white-noise perturbations are kept sufficiently small, the linearized theory works well. These predictions should be testable in the laboratory using a current-clamped cell configuration. If confirmed, then the proximity of a neuron to its spike-transition point can be judged by measuring its subthreshold susceptibility to white-noise stimulation. We postulate that such temporally correlated fluctuations could provide a means of subthreshold signaling via gap-junction connections with neighboring neurons. PMID- 17279953 TI - Knotting probability of a shaken ball-chain. AB - We study the formation of knots on a macroscopic ball chain, which is shaken on a horizontal plate at 12 times the acceleration of gravity. We find that above a certain critical length, the knotting probability is independent of chain length, while the time to shake out a knot increases rapidly with chain length. The probability of finding a knot after a certain time is the result of the balance of these two processes. In particular, the knotting probability tends to a constant for long chains. PMID- 17279955 TI - Electric-field correlation in quantum charged fluids coupled to the radiation field. AB - In a recent paper [S. El Boustani, P. R. Buenzli, and P. A. Martin, Phys. Rev. E 73, 036113 (2006)] about quantum charges in equilibrium with radiation, among other things the asymptotic form of the electric-field correlation has been obtained by a microscopic calculation. It has been found that this correlation has a long-range algebraic decay of the form 1/r3 (except in the classical limit). The macroscopic approach, in the Course of Theoretical Physics of Landau and Lifshitz, gives no such decay. In this Brief Report we revisit and complete the macroscopic approach of Landau and Lifshitz and suggest that, perhaps, the use of a classical electromagnetic field by El Boustani was not justified. PMID- 17279954 TI - Changing the heat conductivity: an analytical study. AB - We address the problem of controlling the energy flow in lattice systems: we investigate, in an analytical approach, the properties of the heat conductivity of the harmonic crystal with self-consistent stochastic reservoirs, a single model with normal conductivity. For the case of weak interparticle interaction, in a perturbative analysis, we obtain an expression for the thermal conductivity and show how to decrease and/or increase the heat current inside the system by changing the masses of the particles and/or the on-site potentials. These results may be useful in the construction of devices controlling the heat conduction. PMID- 17279957 TI - Relaxation time for the ionic current in a nematic cell under a large electric field. AB - We evaluate the ionic relaxation time of a nematic cell subjected to a potential difference, V0 , very large with respect to VT=KBT/q=0.025 V, where KBT is the thermal energy, and q the electrical charge of the ions, assumed monovalent. The analysis is performed by assuming that the mobilities of the positive and negative ions are the same, and that the ions can be considered pointlike. We show that, for V0>>VT, the relaxation time tends to the time of flight of the ions. In our analysis the ionic charges are assumed to form two surface layers responsible for a partial screening of the external field. In this framework, the evolution of the surface-charge density is determined by a simple differential equation related to the conservation of the ions number. According to our calculations, the relaxation time of the surface density of ionic origin, and of the electrical potential close to the electrodes, depends on the applied voltage, in agreement with the experimental observations. PMID- 17279956 TI - Phase diagram of the hard-core Yukawa fluid within the integral equation method. AB - In this study, the integral equation method proposed recently by Sarkisov [J. Chem. Phys. 114, 9496 (2001).], which has proved accurate for continuous potentials, is extended successfully to the hard sphere potential plus an attractive Yukawa tail. By comparing the results of thermodynamic properties, including the liquid-vapor phase diagram, with available simulation data, it is found that this method remains reliable for this class of models of interaction often used in colloid science. PMID- 17279958 TI - Orthotropic elastic shell model for buckling of microtubules. AB - In view of the fact that microtubules exhibit strong anisotropic elastic properties, an orthotropic elastic shell model for microtubules is developed to study buckling behavior of microtubules. The predicted critical pressure is found to agree well with recent unexplained experimental data on pressure-induced buckling of microtubules [Needleman, Phys. Rev. Lett. 93, 198104 (2004); Biophys. J. 89, 3410 (2005)] which are lower than that predicted by the isotropic shell model by four orders of magnitude. General buckling behavior of microtubules under axial compression or radial pressure is studied. The results show that the isotropic shell model greatly overestimates the bucking loads of microtubules, except columnlike axially compressed buckling of long microtubules (of length-to diameter ratio larger than, say, 150). In particular, the present results also offer a plausible explanation for the length dependency of flexibility of microtubules reported in the literature. PMID- 17279959 TI - Correlations in weighted networks. AB - We develop a statistical theory to characterize correlations in weighted networks. We define the appropriate metrics quantifying correlations and show that strictly uncorrelated weighted networks do not exist due to the presence of structural constraints. We also introduce an algorithm for generating maximally random weighted networks with arbitrary P(k,s) to be used as null models. The application of our measures to real networks reveals the importance of weights in a correct understanding and modeling of these heterogeneous systems. PMID- 17279960 TI - Frequency locking and complex dynamics near a periodically forced robust heteroclinic cycle. AB - Robust heteroclinic cycles occur naturally in many classes of nonlinear differential equations with invariant hyperplanes. In particular they occur frequently in models for ecological dynamics and fluid mechanical instabilities. We consider the effect of small-amplitude time-periodic forcing and describe how to reduce the dynamics to a two-dimensional map. In the limit where the heteroclinic cycle loses asymptotic stability, intervals of frequency locking appear. In the opposite limit, where the heteroclinic cycle becomes strongly stable, the dynamics remains chaotic and no frequency locking is observed. PMID- 17279961 TI - Microwave generation of stable atmospheric-pressure fireballs in air. AB - The generation of stable buoyant fireballs in a microwave cavity in air at atmospheric pressure without the use of vaporized solids is described. These fireballs have some of the characteristics of ball lightning and resemble those reported by Dikhtyar and Jerby [Phys. Rev. Lett. 96, 045002 (2006)], although of a different color, and do not require the presence of molten or vaporized material. Mechanisms of microwave plasma formation and fluid dynamics can account for the observed behavior of the fireballs, which do not appear to meet the accepted definition of dusty plasmas in this case. Relevance to models of ball lightning and industrial applications are discussed. PMID- 17279962 TI - Spreading dynamics on small-world networks with connectivity fluctuations and correlations. AB - Infectious diseases and computer malwares spread among humans and computers through the network of contacts among them. These networks are characterized by wide connectivity fluctuations, connectivity correlations, and the small-world property. In a previous work [Phys. Rev. Lett. 96, 038702 (2006)] I have shown that the connectivity fluctuations together with the small-world property lead to a spreading law characterized by an initial power law growth with an exponent determined by the average node distance on the network. Here I extend these results to consider the influence of connectivity correlations which are generally observed in real networks. I show that assortative and disassortative connectivity correlations enhance and diminish, respectively, the range of validity of this spreading law. As a corollary I obtain the region of connectivity fluctuations and degree correlations characterized by the absence of an epidemic threshold. These results are relevant for the spreading of infectious diseases, rumors, and information among humans and the spreading of computer viruses, email worms, and hoaxes among computer users. PMID- 17279963 TI - Kinetics of migration-driven aggregation processes on scale-free networks. AB - We propose a solvable model for the migration-driven aggregate growth on completely connected scale-free networks. A reversible migration system is considered with the produce rate kernel K(k;l|i;j) approximately k(u)i(upsilon)(lj)(nu) or the generalized kernel K(k;l|i;j) approximately (k(upsilon)i(omega)+k(omega)i(upsilon)(lj)(nu), at which an i-mer aggregate locating on the node with j links gains one monomer from a k-mer aggregate locating on the node with l links. It is found that the evolution behavior of the system depends crucially on the details of the rate kernel. In some cases, the aggregate size distribution approaches a scaling form and the typical size S(t,l) of the aggregates locating on the nodes with l links grows infinitely with time; while in other cases, a gelation transition may emerge in the system at a finite critical time. We also introduce a simplified model, in which the aggregates independently gain or lose one monomer at the rate I(1)(k;l)=I(2)(k;l) proportional to k(omega)l(nu), and find the similar results. Most intriguingly, these models exhibit that the evolution behavior of the total distribution of the aggregates with the same size is drastically different from that for the corresponding system in normal space. We test our analytical results with the population data of all counties in the U.S. during the past century and find good agreement between the theoretical predictions and the realistic data. PMID- 17279964 TI - von Neumann entropy and localization-delocalization transition of electron states in quantum small-world networks. AB - The von Neumann entropy for an electron in periodic, disorder, and quasiperiodic quantum small-world networks (QSWN's) is studied numerically. For the disorder QSWN's, the derivative of the spectrum-averaged von Neumann entropy is maximal at a certain density of shortcut links p*, which can be as a signature of the localization-delocalization transition of electron states. The transition point p* is agreement with that obtained by the level statistics method. For the quasiperiodic QSWN's, it is found that there are two regions of the potential parameter. The behaviors of electron states in different regions are similar to that of periodic and disorder QSWN's, respectively. PMID- 17279965 TI - Optimal paths in complex networks with correlated weights: the worldwide airport network. AB - We study complex networks with weights w(ij) associated with each link connecting node i and j. The weights are chosen to be correlated with the network topology in the form found in two real world examples: (a) the worldwide airport network and (b) the E. Coli metabolic network. Here w(ij) approximately equals x(ij)(k(i)k(j))alpha, where k(i) and k(j) are the degrees of nodes i and j , x(ij) is a random number, and alpha represents the strength of the correlations. The case alpha >0 represents correlation between weights and degree, while alpha< 0 represents anticorrelation and the case alpha=0 reduces to the case of no correlations. We study the scaling of the lengths of the optimal paths, l(opt), with the system size N in strong disorder for scale-free networks for different alpha. We find two different universality classes for l(opt), in strong disorder depending on alpha: (i) if alpha >0 , then for lambda >2 the scaling law l(opt) approximately equals N(1/3), where lambda is the power-law exponent of the degree distribution of scale-free networks, and (ii) if alpha< or =0 , then l(opt) approximately equals N((nu)(opt)) with nu(opt) identical to its value for the uncorrelated case alpha=0. We calculate the robustness of correlated scale-free networks with different alpha and find the networks with alpha< 0 to be the most robust networks when compared to the other values of alpha. We propose an analytical method to study percolation phenomena on networks with this kind of correlation, and our numerical results suggest that for scale-free networks with alpha< 0 , the percolation threshold p(c) is finite for lambda >3, which belongs to the same universality class as alpha=0 . We compare our simulation results with the real worldwide airport network, and we find good agreement. PMID- 17279966 TI - Dissemination strategy for immunizing scale-free networks. AB - We consider the problem of distributing a vaccine for immunizing a scale-free network against a given virus or worm. We introduce a method, based on vaccine dissemination, that seems to reflect more accurately what is expected to occur in real-world networks. Also, since the dissemination is performed using only local information, the method can be easily employed in practice. Using a random-graph framework, we analyze our method both mathematically and by means of simulations. We demonstrate its efficacy regarding the trade-off between the expected number of nodes that receive the vaccine and the network's resulting vulnerability to develop an epidemic as the virus or worm attempts to infect one of its nodes. For some scenarios, the method is seen to render the network practically invulnerable to attacks while requiring only a small fraction of the nodes to receive the vaccine. PMID- 17279967 TI - Collective oscillations, bicluster motion, and dynamical order in a system of globally coupled rotors with repulsive interactions. AB - We perform extensive numerical simulations on a system of globally coupled rotors with repulsive interactions. By controlling systematically initial conditions, we determine the criterion for the emergence of bicluster motion. It is found that stable bicluster motion emerges at low temperatures, where the initial kinetic energy accounts for less than about 60% of the total energy. Also observed are collective oscillations of the potential energy and the magnetization, which are persistent. With appropriately chosen initial conditions, the system exhibits characteristic motion where biclusters keep forming and disappearing continually. It is argued that such bicluster motion is closely related to the dynamical order suggested recently. PMID- 17279969 TI - Nonequilibrium phase transition in the coevolution of networks and opinions. AB - Models of the convergence of opinion in social systems have been the subject of considerable recent attention in the physics literature. These models divide into two classes, those in which individuals form their beliefs based on the opinions of their neighbors in a social network of personal acquaintances, and those in which, conversely, network connections form between individuals of similar beliefs. While both of these processes can give rise to realistic levels of agreement between acquaintances, practical experience suggests that opinion formation in the real world is not a result of one process or the other, but a combination of the two. Here we present a simple model of this combination, with a single parameter controlling the balance of the two processes. We find that the model undergoes a continuous phase transition as this parameter is varied, from a regime in which opinions are arbitrarily diverse to one in which most individuals hold the same opinion. PMID- 17279968 TI - Characteristics of reaction-diffusion on scale-free networks. AB - We examine some characteristic properties of reaction-diffusion processes of the A+A-->0 type on scale-free networks. Due to the inhomogeneity of the structure of the substrate, as compared to usual lattices, we focus on the characteristics of the nodes where the annihilations occur. We show that at early times the majority of these events take place on low-connectivity nodes, while as time advances the process moves towards the high-connectivity nodes, the so-called hubs. This pattern remarkably accelerates the annihilation of the particles, and it is in agreement with earlier predictions that the rates of reaction-diffusion processes on scale-free networks are much faster than the equivalent ones on lattice systems. PMID- 17279970 TI - Behaviors of susceptible-infected epidemics on scale-free networks with identical infectivity. AB - In this paper, we propose a susceptible-infected model with identical infectivity, in which, at every time step, each node can only contact a constant number of neighbors. We implemented this model on scale-free networks, and found that the infected population grows in an exponential form with the time scale proportional to the spreading rate. Furthermore, by numerical simulation, we demonstrated that the targeted immunization of the present model is much less efficient than that of the standard susceptible-infected model. Finally, we investigate a fast spreading strategy when only local information is available. Different from the extensively studied path-finding strategy, the strategy preferring small-degree nodes is more efficient than that preferring large-degree nodes. Our results indicate the existence of an essential relationship between network traffic and network epidemic on scale-free networks. PMID- 17279971 TI - Statistical mechanics of error exponents for error-correcting codes. AB - Error exponents characterize the exponential decay, when increasing message length, of the probability of error of many error-correcting codes. To tackle the long-standing problem of computing them exactly, we introduce a general, thermodynamic, formalism that we illustrate with maximum-likelihood decoding of low-density parity-check codes on the binary erasure channel and the binary symmetric channel. In this formalism, we apply the cavity method for large deviations to derive expressions for both the average and typical error exponents, which differ by the procedure used to select the codes from specified ensembles. When decreasing the noise intensity, we find that two phase transitions take place, at two different levels: a glass to ferromagnetic transition in the space of codewords and a paramagnetic to glass transition in the space of codes. PMID- 17279972 TI - Thermodynamics of spin systems on small-world hypergraphs. AB - We study the thermodynamic properties of spin systems on small-world hypergraphs, obtained by superimposing sparse Poisson random graphs with p -spin interactions onto a one-dimensional Ising chain with nearest-neighbor interactions. We use replica-symmetric transfer-matrix techniques to derive a set of fixed-point equations describing the relevant order parameters and free energy, and solve them employing population dynamics. In the special case where the number of connections per site is of the order of the system size, we are able to solve the model analytically. In the more general case where the number of connections is finite, we determine the static and dynamic ferromagnetic-paramagnetic transitions using population dynamics. The results are tested against Monte-Carlo simulations. PMID- 17279973 TI - Sparse repulsive coupling enhances synchronization in complex networks. AB - Through the last years, different strategies to enhance synchronization in complex networks have been proposed. In this work, we show that synchronization of nonidentical dynamical units that are attractively coupled in a small-world network is strongly improved by just making phase-repulsive a tiny fraction of the couplings. By a purely topological analysis that does not depend on the dynamical model, we link the emerging dynamical behavior with the structural properties of the sparsely coupled repulsive network. PMID- 17279974 TI - Memory-based snowdrift game on networks. AB - We present a memory-based snowdrift game (MBSG) taking place on networks. We found that, when a lattice is taken to be the underlying structure, the transition of spatial patterns at some critical values of the payoff parameter is observable for both four- and eight-neighbor lattices. The transition points as well as the styles of spatial patterns can be explained by local stability analysis. In sharp contrast to previously reported results, cooperation is promoted by the spatial structure in the MBSG. Interestingly, we found that the frequency of cooperation of the MBSG on a scale-free network peaks at a specific value of the payoff parameter. This phenomenon indicates that properly encouraging selfish behaviors can optimally enhance the cooperation. The memory effects of individuals are discussed in detail and some non-monotonous phenomena are observed on both lattices and scale-free networks. Our work may shed some new light on the study of evolutionary games over networks. PMID- 17279975 TI - Clustering in complex networks. I. General formalism. AB - We develop a full theoretical approach to clustering in complex networks. A key concept is introduced, the edge multiplicity, that measures the number of triangles passing through an edge. This quantity extends the clustering coefficient in that it involves the properties of two-and not just one-vertices. The formalism is completed with the definition of a three-vertex correlation function, which is the fundamental quantity describing the properties of clustered networks. The formalism suggests different metrics that are able to thoroughly characterize transitive relations. A rigorous analysis of several real networks, which makes use of this formalism and the metrics, is also provided. It is also found that clustered networks can be classified into two main groups: the weak and the strong transitivity classes. In the first class, edge multiplicity is small, with triangles being disjoint. In the second class, edge multiplicity is high and so triangles share many edges. As we shall see in the following paper, the class a network belongs to has strong implications in its percolation properties. PMID- 17279976 TI - Clustering in complex networks. II. Percolation properties. AB - The percolation properties of clustered networks are analyzed in detail. In the case of weak clustering, we present an analytical approach that allows us to find the critical threshold and the size of the giant component. Numerical simulations confirm the accuracy of our results. In more general terms, we show that weak clustering hinders the onset of the giant component whereas strong clustering favors its appearance. This is a direct consequence of the differences in the k core structure of the networks, which are found to be totally different depending on the level of clustering. An empirical analysis of a real social network confirms our predictions. PMID- 17279977 TI - Designing threshold networks with given structural and dynamical properties. AB - The threshold model can be used to generate random networks of arbitrary size with given local properties such as the degree distribution, clustering, and degree correlation. We summarize the properties of networks created using the threshold model and present an alternative deterministic construction. These networks are threshold graphs and therefore contain a highly compressible layered structure and allow computation of important network properties in linear time. We show how to construct arbitrarily large, sparse, threshold networks with (approximately) any prescribed degree distribution or Laplacian spectrum. Control of the spectrum allows careful study of the synchronization properties of threshold networks including the relationship between heterogeneous degrees and resistance to synchrony. PMID- 17279978 TI - Time delay in the Kuramoto model with bimodal frequency distribution. AB - We investigate the effects of a time-delayed all-to-all coupling scheme in a large population of oscillators with natural frequencies following a bimodal distribution. The regions of parameter space corresponding to synchronized and incoherent solutions are obtained both numerically and analytically for particular frequency distributions. In particular, we find that bimodality introduces a new time scale that results in a quasiperiodic disposition of the regions of incoherence. PMID- 17279979 TI - Quasiregularity and rigorous diffusion of strong Hamiltonian chaos. AB - Exact results are derived concerning quasiregularity and diffusion of strong chaos on resonances of the sawtooth map. A chaotic ensemble of well-defined quasiregularity type (the sequence of resonances visited) is generally a fractal set whose main characteristics, the topological entropy and the Hausdorff dimension, are calculated exactly, under some conditions, using a symbolic dynamics. The effect of quasiregularity on chaotic diffusion is characterized by an infinity of diffusion coefficients, each associated with a fractal ensemble trapped in a periodic set of resonances. In some cases, these coefficients are calculated exactly and it is shown that rigorous diffusion takes place on the resonances. PMID- 17279980 TI - Calculation of cantori for Hamiltonian flows. AB - Cantori are the invariant sets remaining after the destruction of KAM surfaces and create partial barriers to transport in chaotic regions. Cantori may be approximated by high-order periodic orbits; however, field line tracing methods for locating periodic orbits perform poorly in chaotic regions. To approximate cantori for continuous flow dynamics, high-order periodic orbits are determined by Lagrangian variational methods. The method is robust to chaos, converges quadratically, and the computational cost scales linearly with the periodicity length of the orbit. Minimizing-periodic orbits with periodicities in the tens of thousands, that closely approximate cantori, have been constructed. PMID- 17279981 TI - Phase rigidity and avoided level crossings in the complex energy plane. AB - We consider the effective Hamiltonian of an open quantum system, its biorthogonal eigenfunctions phi(lambda), and define the value r(lambda)=(phi(lambda)|phi(lambda))/ that characterizes the phase rigidity of the eigenfunctions phi(lambda). In the scenario with avoided level crossings, r(lambda) varies between 1 and 0 due to the mutual influence of neighboring resonances. The variation of r(lambda) is an internal property of an open quantum system. In the literature, the phase rigidity rho of the scattering wave function Psi(C)(E) is considered. Since Psi(C)(E) can be represented in the interior of the system by the phi(lambda), the phase rigidity rho of the Psi(C)(E) is related to the r(lambda) and therefore also to the mutual influence of neighboring resonances. As a consequence, the reduction of the phase rigidity rho to values smaller than 1 should be considered, at least partly, as an internal property of an open quantum system in the overlapping regime. The relation to measurable values such as the transmission through a quantum dot, follows from the fact that the transmission is, in any case, resonant at energies that are determined by the real part of the eigenvalues of the effective Hamiltonian. We illustrate the relation between phase rigidity rho and transmission numerically for small open cavities. PMID- 17279982 TI - Synchronization and beam forming in an array of repulsively coupled oscillators. AB - We study the dynamics of an array of Stuart-Landau oscillators with repulsive coupling. Autonomous network with global repulsive coupling settles on one from a continuum of synchronized regimes characterized by zero mean field. Driving this array by an external oscillatory signal produces a nonzero mean field that follows the driving signal even when the oscillators are not locked to the external signal. At sufficiently large amplitude the external signal synchronizes the oscillators and locks the phases of the array oscillations. Application of this system as a beam-forming element of a phase array antenna is considered. The phase dynamics of the oscillator array synchronization is used to reshape the phases of signals received from the phase array antenna and improve its beam pattern characteristics. PMID- 17279983 TI - Persistent localized states for a chaotically mixed bistable reaction. AB - We describe the evolution of a bistable chemical reaction in a closed two dimensional chaotic laminar flow, from a localized initial disturbance. When the fluid mixing is sufficiently slow, the disturbance may spread and eventually occupy the entire fluid domain. By contrast, rapid mixing tends to dilute the initial state and so extinguish the disturbance. Such a dichotomy is well known. However, we report here a hitherto apparently unremarked intermediate case, a persistent highly localized disturbance. Such a localized state arises when the Damkohler number is great enough to sustain a "hot spot," but not so great as to lead to global spread. We show that such a disturbance is located in the neighborhood of an unstable periodic orbit of the flow, and we describe some limited aspects of its behavior using a reduced, lamellar model. PMID- 17279984 TI - Nonperiodic echoes from mushroom billiard hats. AB - Mushroom billiards have the remarkable property to show one or more clear cut integrable islands in one or several chaotic seas, without any fractal boundaries. The islands correspond to orbits confined to the hats of the mushrooms, which they share with the chaotic orbits. It is thus interesting to ask how long a chaotic orbit will remain in the hat before returning to the stem. This question is equivalent to the inquiry about delay times for scattering from the hat of the mushroom into an opening where the stem should be. For fixed angular momentum we find that no more than three different delay times are possible. This induces striking nonperiodic structures in the delay times that may be of importance for mesoscopic devices and should be accessible to microwave experiments. PMID- 17279985 TI - Quantum-to-classical transition in a system with mixed classical dynamics. AB - We study how decoherence rules the quantum-classical transition of the kicked harmonic oscillator. The system presents classical dynamics that ranges from regular to strong chaotic behavior depending on the amplitude of the kicks. We show that for regular and mixed classical dynamics, and in the presence of noise, the distance between the classical and quantum phase space distributions is proportional to a single parameter chi identical to K Planck's (eff)(2)/4D(3/2) , which relates the effective Planck constant, Planck's (eff), to the kicking strength, K, and the diffusion constant, D. This relation between classical and quantum distributions is valid when chi<1 , a case that is always attainable in the semiclassical regime, independent of the value of the strength of noise given by D. Our results extend a recent study performed in the chaotic regime. PMID- 17279986 TI - Method for determining a coupling function in coupled oscillators with application to Belousov-Zhabotinsky oscillators. AB - A coupling function that describes the interaction between self-sustained oscillators in a phase equation is derived and applied experimentally to Belousov Zhabotinsky (BZ) oscillators. It is demonstrated that the synchronous behavior of coupled BZ reactors is explained extremely well in terms of the coupling function thus obtained. This method does not require comprehensive knowledge of either the oscillation mechanism or the interaction among the oscillators, both of these being often difficult to elucidate in an actual system. These facts enable us to accurately analyze the weakly coupled entrainment phenomenon through the direct measurement of the coupling function. PMID- 17279987 TI - Vorticity generation in creeping flow past a magnetic obstacle. AB - The generation of vorticity in the two-dimensional creeping flow of an incompressible, electrically conducting viscous fluid past a localized magnetic field distribution is analyzed under the low magnetic Reynolds number approximation. It is shown that the Lorentz force produced by the interaction of the induced electric currents with the nonuniform magnetic field acts as an obstacle for the flow, creating different steady flow patterns that are reminiscent of those observed in the flow past bluff bodies. First, analytic solutions are obtained for a creeping flow past a magnetic point dipole, modeled as a Gaussian distribution. Using a perturbation scheme, the vorticity is expressed as an expansion in the small Reynolds number, and first- and second order approximations are calculated. The induced magnetic field, pressure, and stream function are also determined. Further, full numerical finite difference solutions are obtained for a uniform creeping flow past a finite size magnetic field distribution produced by a square magnetized plate. Hartmann numbers in the range 1< or =Ha< or =100 are explored. Depending on the strength of the magnetic force, stagnation zones or steady vortical structures are obtained. The analysis contributes to the understanding of flows in nonuniform magnetic fields and flows produced by localized forces. PMID- 17279988 TI - Helical magnetorotational instability in magnetized Taylor-Couette flow. AB - Hollerbach and Rudiger have reported a new type of magnetorotational instability (MRI) in magnetized Taylor-Couette flow in the presence of combined axial and azimuthal magnetic fields. The salient advantage of this "helical" MRI (HMRI) is that marginal instability occurs at arbitrarily low magnetic Reynolds and Lundquist numbers, suggesting that HMRI might be easier to realize than standard MRI (axial field only), and that it might be relevant to cooler astrophysical disks, especially those around protostars, which may be quite resistive. We confirm previous results for marginal stability and calculate HMRI growth rates. We show that in the resistive limit, HMRI is a weakly destabilized inertial oscillation propagating in a unique direction along the axis. But we report other features of HMRI that make it less attractive for experiments and for resistive astrophysical disks. Large axial currents are required. More fundamentally, instability of highly resistive flow is peculiar to infinitely long or periodic cylinders: finite cylinders with insulating endcaps are shown to be stable in this limit, at least if viscosity is neglected. Also, Keplerian rotation profiles are stable in the resistive limit regardless of axial boundary conditions. Nevertheless, the addition of a toroidal field lowers thresholds for instability even in finite cylinders. PMID- 17279989 TI - Pore-network study of methane hydrate dissociation. AB - A two-dimensional pore-network model based on invasion percolation is used to study the patterns obtained from the release of methane during the dissociation of methane hydrates (without including dissociation kinetics) caused by a sudden pressure reduction in the system below the hydrate equilibrium pressure. The concept of the critical gas saturation S(gc) (volume fraction of the gas phase at the onset of bulk gas flow) is introduced to analyze gas hydrate dissociation. The effects of throat-size distribution (corresponding to off-shore oceanic sediments or on-shore sediments under permafrost), applied pressure difference across the network, and initial hydrate saturation on the resulting gas patterns and on the critical gas saturation are examined to determine the possibility of producing methane. As expected, large throat sizes or wide throat distributions, large pressure drops, and higher initial hydrate saturation act as promoters for the production of the released gas. For typical deep ocean sediments with small pore sizes and low hydrate saturation, it may be difficult to produce methane resulting from hydrate dissociation. PMID- 17279990 TI - Linking drainage front morphology with gaseous diffusion in unsaturated porous media: a lattice Boltzmann study. AB - The effect of drainage front morphology on gaseous diffusion through partially saturated porous media is analyzed using the lattice Boltzmann method (LBM). Flow regimes for immiscible displacement in porous media have been characterized as stable displacement, capillary fingering, and viscous fingering. The dominance of a flow regime is associated with the relative magnitudes of gravity, viscous, and capillary forces, quantifiable via the Bond number Bo, capillary number Ca, and their difference, Bo-Ca . Forced drainage from an initially saturated two dimensional (2D) porous medium was simulated and the resulting flow patterns were analyzed and compared with theoretical predictions and experimental results. The LBM simulations reproduced expected flow morphologies for a range of drainage velocities and gravitational forces (i.e., a range of capillary and Bond numbers). Furthermore, measures of drainage front width as a function of the dimensionless difference Bo-Ca correspond well with scaling laws derived from percolation theory. Effects of flow morphology on residual fluid entrapment and gaseous diffusion were assessed by running LBM diffusion simulations through the partially saturated domain for a range of water contents. The effective diffusion coefficient as a function of water content was estimated for three regimes: stable drainage front, capillary fingering, and viscous fingering. Significant reductions in gaseous diffusion coefficient were found for viscous fingering relative to stable displacement, and to a lesser extent for capillary fingering, indicating that wetting phase distribution with a high degree of fingering in the 2D domain severely restricts connectivity of gas diffusion pathways through the medium. The study lends support for the use of LBM in design and management of fluids in porous media under variable gravity, and enhances the understanding of the role of dynamic fluid behavior on macroscopic transport properties of partially saturated porous media. PMID- 17279991 TI - Experiments on the rapid mechanical expansion of liquid 4He through its superfluid transition. AB - Phenomena following a rapid mechanical quench of liquid 4He from its normal to its superfluid phase are reported and discussed. The mechanical expansion apparatus is an improved version of that described previously. It uses a double cell geometry to effect a partial separation of the sample from the convolutions of the bellows that form the outer wall of the cell. Consistent with earlier work, no evidence is found for the production of quantized vortices via the Kibble-Zurek (KZ) mechanism. Although the expansion is complete within 15ms , the second-sound velocity and attenuation continue to increase for a further approximately 60ms ; correspondingly the temperature decreases. Subsequently, the temperature rises again toward its final value as the second-sound velocity and attenuation decrease. It is shown that this unexpected behavior is apparently associated with a large-amplitude second-sound oscillation produced by the expansion, and it is suggested that the observed vortices are created by the normal fluid-superfluid counterflow that constitutes the second-sound wave. If production of large-amplitude second sound is inherent to the mechanical expansion of liquid 4He through the superfluid transition, as appears to be the case for final temperatures more than 3mK from the lambda transition, the phenomenon sets a lower bound on the density of KZ vortices that can be detected in this type of experiment. PMID- 17279992 TI - Heat flux intensification by vortical flow localization in rotating convection. AB - The effect of rotation on turbulent convective flow between parallel plates has been assessed with direct numerical simulations. With increasing rotation-rate an interesting transition is observed in the vertical-velocity skewness. This transition indicates a localization of motion directed away from the wall and correlates well with changes observed in the heat flux, as well as in the thermal and viscous boundary layer thicknesses. The formation of localized intense vortical structures provides for intensified vertical heat transport through Ekman pumping. At higher rotation-rates this is counteracted by the inhibition of vertical motion by rotation as expressed in the geostrophic thermal-wind balance. PMID- 17279993 TI - Negative wake behind a sphere rising in viscoelastic fluids: a lattice Boltzmann investigation. AB - We investigate the complex flow field around a sphere rising in a Maxwell fluid by means of the lattice Boltzmann simulation to provide insights into the strange negative wake experimentally observed behind a bubble or particle in non Newtonian fluids. The influence of the rise velocity, sphere diameter, and fluid's rheology is considered through two dimensionless numbers: the Deborah number De and the Reynolds number Re. Our simulation shows that the negative wake appears behind the sphere when De>2 . On the other hand, the shape of the negative wake described by the opening angle theta of the upward flow cone surrounding the negative wake is mainly determined by the Reynolds number Re. These results reveal that the physical origin of the negative wake stems mainly from the competition between the elastic and viscous stresses in the fluid. PMID- 17279994 TI - Comparisons between different approximations to energy dissipation rate in a self preserving far wake. AB - By using a four-hot-wire probe and an eight-hot-wire probe, different approximations to energy dissipation rate have been made in the far field of a cylinder wake. The appropriateness of the various approximations is evaluated by examining their mean values, spectra, conditional analysis, and scaling range exponents. It is found that there are significant differences between the instantaneous values of E(iso), the isotropic dissipation rate, and other approximations. The present measurements also allow the examination of the spatial correlation between the energy dissipation rate and the enstrophy Omega. While the correlation between E(iso) and Omega is low, there is a strong correlation between the other approximations to energy dissipation rate and the enstrophy Omega. The scaling range exponents show that the substitutes to the energy dissipation rate and enstrophy based on isotropy are more intermittent than their corresponding true values. The present results suggest that using E(iso) as a substitute of should be re-examined, especially for the instantaneous values. PMID- 17279996 TI - Nonintrusive characterization of the azimuthal drift current in a coaxial ExB discharge plasma. AB - A diagnostic is developed for the nonintrusive study of the azimuthal drift current in the coaxial ExB discharge of a Hall plasma accelerator. The technique of fast current interruption is used to generate a signal on several loop antenna that circle the outer wall of the discharge channel. The signal on the antenna is recorded, and used to determine the spatial distribution of the azimuthal drift at the moment of current interruption. The results of the experiment are compared to estimates derived via prior intrusive measurements, and the intrusive estimates are found to predict the spatial characteristics of the azimuthal drift, but underestimate its total magnitude. The self-induced magnetic field is then calculated and added to the applied magnetic field. The peak total magnetic field is seen to shift 2-5mm towards the anode due to self-induction, and suffer a reduction in magnitude of 10%-15%. The peak in the total magnetic field is then found to more closely coincide with the peak of the measured electric field than the peak of the vacuum magnetic field. It is concluded that the self-induced magnetic field could be important to anomalous electron mobility in the Hall effect thruster, and simulation efforts should try to include its impact. PMID- 17279995 TI - Multiple void formation in plasmas containing multispecies charged grains. AB - Self-organized separation of charged-dust species in two-dimensional dusty plasmas is studied by means of molecular-dynamics simulation. The multispecies dust grains, interacting through a screened Coulomb potential with a long-range attractive component, are confined by an external quadratic potential and subjected to a radially outward ion drag force. It is found that, in general, the species are spatially separated by bandlike dust-free (or void) regions, and grains of the same species tend to populate a common shell. At large ion drag and/or large plasma screening, a central disklike void as well as concentric bandlike voids separating the different species appear. Because of the outward drag and the attractive component of the dust-dust interaction forces, highly asymmetrical states consisting of species-separated dust clumps can also exist despite the fact that all the forces are either radial or central. PMID- 17279997 TI - Ground state of a confined Yukawa plasma. AB - The ground state of an externally confined one-component Yukawa plasma is derived analytically. In particular, the radial density profile is computed. The results agree very well with computer simulations of three-dimensional spherical Coulomb crystals. We conclude in presenting an exact equation for the density distribution for a confinement potential of arbitrary geometry. PMID- 17279998 TI - Nonadiabatic tunneling in ponderomotive barriers. AB - Localized regions of intense large-scale radiofrequency field are known to act like effective ("ponderomotive") potential barriers, which scatter particles elastically and in the direction determined by the particle initial velocity rather than phase. In smaller-scale fields, transmission through a ponderomotive barrier is probabilistic and resembles tunneling of a quantum particle through a static potential. We derive asymptotic expressions for the phase-averaged transmission coefficient T as a function of the particle energy E0. We show that, unlike for a truly quantum particle, T(E0) is of algebraic form and has a threshold, below which transmission does not occur. We also find a threshold in E0, above which all particles are transmitted regardless of their initial phase. PMID- 17279999 TI - Transverse dielectric matrix and shear mode dispersion in strongly coupled electronic bilayer liquids. AB - The authors develop a transverse dielectric matrix and from it they calculate the shear mode dispersion in strongly coupled charged-particle bilayer liquids in the T=0 quantum domain. The formulation is based on the classical quasilocalized charge approximation (QLCA) and extends the QLCA formalism into the quantum domain. Its development parallels and complements the development of a similarly extended longitudinal dielectric matrix formalism reported in a recent companion work [K. I. Golden, H. Mahassen, G. J. Kalman, G. Senatore, and F. Rapisarda, Phys. Rev. E 71, 036401 (2005)]. Using pair correlation function data generated from diffusion Monte Carlo simulations, the authors calculate the dispersion of the in-phase and out-of-phase shear modes over a wide range of high-r(s) values and layer separations. Over the coupling range 10< or =r(s)< or =30 and for layer separations 0.2/sqrt[pi(n)]< or =d< or =0.5/sqrt[pi(n)] , the present study predicts the existence of a robust out-of-phase gapped shear mode dispersion in the domain of the q,omega -plane above the left boundary of the RPA single-pair excitation region; under these conditions, the out-of-phase collective excitation is entirely immune to Landau damping and can be safely considered to be mostly unaffected by diffusive-migrational damping. PMID- 17280000 TI - Exotic radiation from a photonic crystal excited by an ultrarelativistic electron beam. AB - We report the observation of an exotic radiation (unconventional Smith-Purcell radiation) from a one-dimensional photonic crystal. The physical origin of the exotic radiation is direct excitation of the photonic bands by an ultrarelativistic electron beam. The spectrum of the exotic radiation follows photonic bands of a certain parity, in striking contrast to the conventional Smith-Purcell radiation, which shows solely a linear dispersion. Key ingredients for the observation are the facts that the electron beam is in an ultrarelativistic region and that the photonic crystal is finite. The origin of the radiation was identified by comparison of experimental and theoretical results. PMID- 17280001 TI - Zener tunneling in two-dimensional photonic lattices. AB - We discuss the interband light tunneling in a two-dimensional periodic photonic structure, as studied recently in experiments for optically induced photonic lattices [Trompeter, Phys. Rev. Lett. 96, 053903 (2006)]. We identify the Zener tunneling regime at the crossing of two Bloch bands, which occurs in the generic case of a Bragg reflection when the Bloch index crosses the edge of the irreducible Brillouin zone. Similarly, higher-order Zener tunneling involves four Bloch bands when the Bloch index passes through a high-symmetry point on the edge of the Brillouin zone. We derive simple analytical models that describe the tunneling effect, and calculate the corresponding tunneling probabilities. PMID- 17280002 TI - Propagation of femtosecond light pulses in a dye solution: nonadherence to the conventional group velocity. AB - Propagation of femtosecond light pulses in a resonant absorption medium is studied. The propagation time of the light pulses was measured in a dye solution by the optical-Kerr-gate method. Nonadherence to the conventional group velocity domega/dk , which is defined in weak absorption region, was found. The observed wavelength dependences of the group delay and the spectral change in the anomalous dispersion region are qualitatively in good agreement with the theoretical prediction obtained from the new definitions of group velocity, which can be clearly defined even in strong absorption region. PMID- 17280003 TI - Self-compression by femtosecond pulse filamentation: experiments versus numerical simulations. AB - We analyze pulse self-compression in femtosecond filaments, both experimentally and numerically. We experimentally demonstrate the compression of 45 fs pulses down to a duration of 7.4 fs at millijoule pulse energies. This sixfold compression in a self-generated filament does not require any means for dispersion compensation and is highly efficient. We compare our results to numerical simulations, providing a complete propagation model that accounts for full dispersion, pressure variations, Kerr nonlinearity and plasma generation in multiphoton and tunnel regimes. The equations are numerically integrated and allow for a quantitative comparison with the experiment. Our experiments and numerical simulations reveal a characteristic spectrotemporal structure of the self-compressed pulses, consisting of a compressible blue wing and an incompressible red pedestal. We explain the underlying mechanism that leads to this structure and examine the scalability of filament self-compression with respect to pulse energy and gas pressure. PMID- 17280004 TI - Analytical cumulant solution of the vector radiative transfer equation investigates backscattering of circularly polarized light from turbid media. AB - The backscattering of circularly polarized light pulses from an infinite uniform scattering medium is studied as a function of helicity of the incident light and size of scatterers in the medium. The approach considers a polarized short pulse of light incident on the scattering medium, and uses an analytical cumulant solution of the vector radiative transfer equation with the phase matrix obtained from the Mie theory to calculate the temporal profile of scattered polarized photons for any position and any angle of detection. The general expression for the scattered photon distribution function is an expansion in spatial cumulants up to an arbitrary high order. Truncating the expansion at the second-order cumulant, a Gaussian analytical approximate expression for the temporal profile of scattered polarized photons is obtained, whose average center position and half width are always exact. The components of scattered light copolarized and cross polarized with that of the incident light can be calculated and used for determining the degree of polarization of the scattered light. The results show that circularly polarized light of the same helicity dominates the backscattered signal when scatterer size is larger than the wavelength of light. For the scatterers smaller than the wavelength, the light of opposite helicity makes the dominant contribution to the backscattered signal. The theoretical estimates are in good agreement with our experimental results. PMID- 17280005 TI - Straight-edge diffraction of Planck radiation. AB - The irradiance diffraction profile of a straight edge is given as a Taylor series in powers of the distance from the geometrical shadow boundary to any point in the profile for monochromatic radiation. The coefficients of the series, which are obtained as simple analytic expressions, are proportional to the real part of a complex number whose phase cycles through a complete period every eight terms in the series. Integration of this series over a Planck distribution of radiation yields the power series for the Planck profile; this derived series has a finite radius of convergence. The asymptotic series for the Planck profile far from the shadow boundary and beyond the radius of convergence of its power series is obtained by analytic continuation of the power series with the aid of a Barnes type of integral representation. PMID- 17280006 TI - Generalized matrix equivalence theorem for polarization theory. AB - A generalized equivalence theorem for polarization theory is formulated and proven. It is shown that anisotropic properties of homogeneous nondepolarizing media can be presented as a combination of four basic mechanisms: linear and circular phase and linear and circular amplitude anisotropy. Expressions for the generalized effect operators of algebraic (or operator) optics are obtained and the inverse problem of crystal optics is solved in terms of physically realizable anisotropy parameters. PMID- 17280007 TI - Symmetry breaking in symmetric and asymmetric double-well potentials. AB - Motivated by recent experimental studies of matter waves and optical beams in double-well potentials, we study the corresponding solutions of the nonlinear Schrodinger equation. Using a Galerkin-type approach, we obtain a detailed handle on the nonlinear solution branches of the problem, starting from the corresponding linear ones, and we predict the relevant bifurcations for both attractive and repulsive nonlinearities. The dynamics of the ensuing unstable solutions is also examined. The results illustrate the differences that arise between the steady states and the bifurcations emerging in symmetric and asymmetric double wells. PMID- 17280008 TI - Effect of amplification on conductance distribution of a disordered waveguide. AB - Introduction of optical gain in a disordered system results in enhanced fluctuations [F(2)=var(g[over])/2] of the dimensionless conductance g[over], similar to the effect of Anderson localization in a passive medium. Using numerical simulations we demonstrate that, despite such qualitative similarity, the whole distribution of the conductance of amplifying random media is drastically different from that of a passive system with the same value of F(2). PMID- 17280009 TI - Spatial correlation functions of random electromagnetic fields in the presence of a semi-infinite isotropic medium. AB - We extend a previous analysis of spatial correlation functions for classical electromagnetic vector fields near a perfectly conducting boundary [Arnaut, Phys. Rev. E, 73, 036604 (2006)] to the case of an isotropic semi-infinite medium with planar interface and characterized by a first-order impedance boundary condition. The analytical results are illustrated with calculations for the case of point separations in the direction perpendicular to the interface. For the incident plus reflected field, the dependence of the complex-valued and inhomogeneous spatial correlation function on the permittivity, permeability, and conductivity of the medium is determined. For the refracted field, the spatial correlation is again complex valued but homogeneous and highly sensitive to the value of the refractive index. Based on the derived dependencies, nonlocal measurement methods for precision characterization of electromagnetic material properties are suggested. The influence of the directionality of incidence for electromagnetic beams is investigated. Narrowing the beam width results in a slower decrease of the amplitude of the correlation function as a function of point separation. Previously obtained asymptotic results for statistically homogeneous random free fields are retrieved as special cases. PMID- 17280010 TI - One-way diffraction grating. AB - Diffraction gratings are elementary tools for much of optics and spectroscopy. Here, at microwave frequencies, we provide a new perspective on these fundamental structures. A transmission diffraction grating is presented that has diffracted beams emanating from one surface only. It can thus function either as a transmission grating with no reflected orders (other than zero) or, in the reverse configuration, as a partially transmitting structure with diffracted orders in reflection only. PMID- 17280011 TI - Bloch vector dependence of the plasma frequency in metallic photonic crystals. AB - In this paper, a wire mesh metallic photonic crystal is modelized as a stack of gratings of period d made of very thin infinitely metallic rods (the conductivity is assumed to be infinite) of radius a (a<>d) . We derive a very accurate formula for the cut wavelength and we show that the plasma frequency in wire photonic crystals depends upon the Bloch vector. This latest formula is checked numerically. PMID- 17280012 TI - Polarization versus spatial characteristics of optical beams at a planar isotropic interface. AB - Three-dimensional monochromatic optical beams of uniform polarization interacting with a planar boundary between two homogeneous, isotropic, and lossless media are analyzed. Generalized Fresnel transmission and reflection coefficients for beam spectra are given. Interrelations induced by cross-polarization coupling between beam profile and phase and beam polarization, or between spin and orbital angular momentum of beams are derived. Beam transmission for normal incidence is discussed in detail. It is shown that elegant Hermite-Gaussian beams of linear polarization and Laguerre-Gaussian beams of circular polarization, all projected on the interface, are normal modes at this interface. Creation and annihilation of these modes at the interface are shown with total angular momentum being conserved on a single photon level. PMID- 17280013 TI - Wave propagation and optical properties in slabs with light-induced free charge carriers. AB - A theoretical analysis on wave propagation and optical properties of slabs with light-induced free charge carriers within a Fabry-Perot framework is presented. The key of the analysis is to attack the wave propagation problem in terms of the time-averaged Poynting vector modulus within the medium through an alternative approach. This fact allows coupling the microscopic (free charge rate) and macroscopic (electromagnetic field evolution) equations self-consistently by means of the nonlinear permittivity and conductivity, which, in turn, depend on the time-averaged Poynting vector modulus. Thereby, the transmittance, reflectance, and absorptive power are derived as functions of the pump intensity and medium thickness. Bistable behavior is found at relatively high excitation intensity for positive values of the nonlinear permittivity coefficient. The bistability enhances for increasing values of such coefficient and weakens for increasing values of nonlinear photoconductivity coefficient. On the contrary, for negative nonlinear permittivity coefficient, bistability does not appear possessing these media mirrorlike behavior. Some possible applications are suggested. PMID- 17280015 TI - Dissipative-particle-dynamics model for two-phase flows. AB - Dissipative particle dynamics (DPD) is a mesoscopic method in which coarse graining is done at the molecular level to capture the physics at the meso level. In this paper, we present a DPD model for two-phase flows involving liquid and vapor phases. The model is based on mean-field theory. Phase segregation between the two phases is simulated by the choice of an equation of state with a van der Waals loop. Surface tension is modeled by a term that depends on higher-order density gradients and accounts for long-range attractive forces. To test the model, we present results from simulations of a liquid layer, several liquid cylinders of varying size to verify the Laplace's law, small- and large-amplitude liquid cylinder oscillations and capillary waves. In all these cases we compare DPD results with results available from analytical solutions. PMID- 17280014 TI - Experimental study of photonic crystals consisting of E-negative and mu-negative materials. AB - E-negative (ENG) and mu-negative (MNG) materials are successfully fabricated by using composite right/left-handed transmission line. The ENG and MNG materials are opaque in experiments, but the completely tunneling phenomenon occurs in the ENG-MNG pair, if the wave impedance and the effective phase shift of ENG and MNG materials are under the conditions of match, respectively. We experimentally confirmed that the photonic crystals consisting of ENG and MNG materials can possess left-handed propagation modes and right-handed propagation modes within forbidden gaps. At the same time, the Bragg gaps for the band-gap indices m=+/-1 and the zero effective phase (zero-Phi(eff)) gaps were also observed. The experimental results agree extremely well with the simulations. PMID- 17280016 TI - Dynamic correlations in stochastic rotation dynamics. AB - The dynamic structure factor, vorticity and entropy density dynamic correlation functions are measured for stochastic rotation dynamics (SRD), a particle based algorithm for fluctuating fluids. This allows us to obtain unbiased values for the longitudinal transport coefficients such as thermal diffusivity and bulk viscosity. The results are in good agreement with earlier numerical and theoretical results, and it is shown for the first time that the bulk viscosity is indeed zero for this algorithm. In addition, corrections to the self-diffusion coefficient and shear viscosity arising from the breakdown of the molecular chaos approximation at small mean free paths are analyzed. In addition to deriving the form of the leading correlation corrections to these transport coefficients, the probabilities that two and three particles remain collision partners for consecutive time steps are derived analytically in the limit of small mean free path. The results of this paper verify that we have an excellent understanding of the SRD algorithm at the kinetic level and that analytic expressions for the transport coefficients derived elsewhere do indeed provide a very accurate description of the SRD fluid. PMID- 17280017 TI - Thermodynamic consistency of liquid-gas lattice Boltzmann simulations. AB - Lattice Boltzmann simulations have been very successful in simulating liquid-gas and other multiphase fluid systems. However, the underlying second-order analysis of the equation of motion has long been known to be insufficient to consistently derive the fourth-order terms that are necessary to represent an extended interface. These same terms are also responsible for thermodynamic consistency- i.e., to obtain a true equilibrium solution with both a constant chemical potential and a constant pressure. In this article we present an equilibrium analysis of nonideal lattice Boltzmann methods of sufficient order to identify those higher-order terms that lead to a lack of thermodynamic consistency. We then introduce a thermodynamically consistent forcing method. PMID- 17280018 TI - Order-N first-principles calculation method for self-consistent ground-state electronic structures of semi-infinite systems. AB - We present an efficient and highly accurate first-principles calculation method with linear system-size scaling to determine the self-consistent ground-state electron-charge densities of nanostructures suspended between semi-infinite bulks by directly minimizing the energy functional. By making efficient use of the advantages of the real-space finite-difference method, we can impose arbitrary boundary conditions on models and employ spatially localized orbitals. These advantages enable us to calculate the ground-state electron-charge densities in semi-infinite systems. Examples of electronic structure calculations for a one dimensional case and a conductance calculation for sodium nanowires are presented. The calculated electronic structure of the one-dimensional system agrees well with the exact analytical solution, and the conduction properties of the sodium nanowires are consistent with experimental and other theoretical results. These results imply that our procedure enables us to accurately compute self-consistent electronic structures of semi-infinite systems. PMID- 17280019 TI - Lattice Boltzmann approach to thermal transpiration. AB - Diffuse reflection boundary conditions are introduced in a thermal lattice Boltzmann model to allow for variable fluid density and temperature along the walls. The capability of this model to capture the main characteristics of the thermal transpiration phenomenon in a box at nonvanishing Knudsen numbers is demonstrated. The thermal creep velocity is found to be proportional to the temperature gradient imposed at the wall, whereas the accuracy of the simulation results are found to be of first or second order, depending on the numerical scheme. PMID- 17280020 TI - Analysis of simulation technique for steady shock waves in materials with analytical equations of state. AB - We calculate and analyze a thermodynamic limit of a multiscale molecular dynamics based scheme that we have developed previously for simulating shock waves. We validate and characterize the performance of the former scheme for several simple cases. Using model equations of state for chemical reactions and kinetics in a gas and a condensed phase explosive, we show that detonation wave profiles computed using the computational scheme are in good agreement with the steady state wave profiles of hydrodynamic direct numerical simulations. We also characterize the stability of the technique when applied to detonation waves and describe a technique for determining the detonation shock speed. PMID- 17280021 TI - Simulation of binary mixtures with the lattice Boltzman method. AB - A lattice Boltzman model for the simulation of binary mixtures is presented. Contrary to previous models, the present formulation is able to simulate mixtures with different Schmidt numbers and arbitrary molecular mass ratio of the components. In the hydrodynamic limit, the Navier-Stokes and the Stefan-Maxwell binary diffusion equations are recovered. The model is used for the simulation of binary diffusion and mixing layers. The results are found to be in good agreement with a derived similarity solution and with the predictions of a transient spectral element code. PMID- 17280022 TI - Coloring random graphs and maximizing local diversity. AB - We study a variation of the graph coloring problem on random graphs of finite average connectivity. Given the number of colors, we aim to maximize the number of different colors at neighboring vertices (i.e., one edge distance) of any vertex. Two efficient algorithms, belief propagation and Walksat, are adapted to carry out this task. We present experimental results based on two types of random graphs for different system sizes and identify the critical value of the connectivity for the algorithms to find a perfect solution. The problem and the suggested algorithms have practical relevance since various applications, such as distributed storage, can be mapped onto this problem. PMID- 17280023 TI - Consequences of imperfect mixing the Gray-Scott model. AB - We study an autocatalytic reaction-diffusion scheme, the Gray-Scott model, when the mixing processes do not homogenize the reactants. Starting from the master equation, we derive the resulting coupled, nonlinear, stochastic partial differential equations that rigorously include the spatiotemporal fluctuations resulting from the interplay between the reaction and mixing processes. The fields are complex and depend on correlated complex noise terms. We implement a method to solve for these complex fields numerically and extract accurate information about the system evolution and stationary states under different mixing regimes. Through this example, we show how the reaction-induced fluctuations interact with the temporal nonlinearities, leading to results that differ significantly from the mean-field (perfectly mixed) approach. This procedure can be applied to an arbitrary nonlinear reaction diffusion scheme. PMID- 17280024 TI - Persistent chaos in high dimensions. AB - An extensive statistical survey of universal approximators shows that as the dimension of a typical dissipative dynamical system is increased, the number of positive Lyapunov exponents increases monotonically and the number of parameter windows with periodic behavior decreases. A subset of parameter space remains where noncatastrophic topological change induced by a small parameter variation becomes inevitable. A geometric mechanism depending on dimension and an associated conjecture depict why topological change is expected but not catastrophic, thus providing an explanation of how and why deterministic chaos persists in high dimensions. PMID- 17280025 TI - Hexagonal superlattice state in dielectric barrier discharge. AB - We report on the observation of a hexagonal superlattice state (HSS) in dielectric barrier discharge in air/argon near atmospheric pressure. It bifurcates directly from the hexagonal state by increasing the applied voltage. The correlation measurements indicate that the HSS is an interleaving of three different transient sublattices. The spatial power spectrum demonstrates that the HSS has two separate wave vectors. The big wave vector and the small wave vector belong to the harmonic mode and the subharmonic mode, respectively, and they obey the triad resonant interaction [abstract: see text]. PMID- 17280026 TI - Chaotic synchronization in large map networks. AB - The chaotic synchronization in n-dimensional large map networks with local coupling and their size stabilities in the node number N-->infinity are studied analytically and numerically. The analytical results show that the chaotic synchronization is stable for N-->infinity in the presence of the external driving or global coupling. The numerical calculations show that, as the driving or global interaction strength increases from zero, the network states have the whole route: spatiotemporal chaotic state --> cluster chaotic synchronous state - > complete chaotic synchronous state --> spatiotemporal pattern --> spatiotemporal chaotic state. PMID- 17280027 TI - Structure analysis of two-dimensional nonlinear self-trapped photonic lattices in anisotropic photorefractive media. AB - We experimentally generate different types of two-dimensional self-trapped photonic lattices in a photorefractive medium and analyze the induced refractive index change using two different methods. One method gives the first experimental Fourier space analysis of both linear and nonlinear self-trapped photonic lattices with periodic phase modulation using partially spatially incoherent multiband excitation of the lattice modes. The other method utilizes the waveguiding properties of the lattice to achieve a real space analysis of the induced refractive index change. The results of both methods are compared. PMID- 17280028 TI - Asymmetric heat conduction through a weak link. AB - We study the heat conduction of two nonlinear lattices joined by a weak harmonic link. When the system reaches a steady state, the heat conduction of the system is decided by the tunneling heat flow through the weak link. We present an analytical analysis by the combination of the self-consistent phonon theory and the heat tunneling transport formalism, and then the tunneling heat flow can be obtained. Moreover, the nonequilibrium molecular dynamics simulations are performed and the simulations results are consistent with the analytical predictions. PMID- 17280029 TI - Scanning the critical fluctuations: application to the phenomenology of the two dimensional XY model. AB - We show how applying field conjugated to the order parameter may act as a very precise probe to explore the probability distribution function of the order parameter. Using this "magnetic-field scanning" on large-scale numerical simulations of the critical two-dimensional XY model, we are able to discard the conjectured double-exponential form of the large-magnetization asymptote. PMID- 17280030 TI - Thermal rectifying effect in macroscopic size. AB - We address the problem of the rectifying effect of heat conduction at macroscopic size. A design for a macroscopic thermal rectifier based on the macroscopic thermal conductivity of materials is introduced, and then realizations of the design are shown by numerical simulations and phenomenological estimations. PMID- 17280031 TI - Small changes in particle-size distribution dramatically delay and enhance nucleation in hard sphere colloidal suspensions. AB - We present hard-sphere crystallization kinetics for three samples with small differences in polydispersity. We show that an increase in polydispersity of 1% is sufficient to cause dramatic changes in the crystallization kinetics: crystallization is delayed by almost one decade in time and quantitative and qualitative changes in the crystallization scenario are observed. Surprisingly the nucleation rate density is enhanced by almost a factor of 10. We interpret these results in terms of polydispersity limited growth, where local fractionation processes lead to a delayed but faster nucleation. PMID- 17280032 TI - Partially asymmetric exclusion processes with sitewise disorder. AB - We study the stationary properties as well as the nonstationary dynamics of the one-dimensional partially asymmetric exclusion process with position-dependent random hop rates. Relating the hop rates to an energy landscape the stationary current J is determined by the largest barrier in a finite system of L sites and the corresponding waiting time tau approximately J{-1} is related to the waiting time of a single random walker, tau_{rw} , as tau approximately tau_{rw}{1/2} . The current is found to vanish as J approximately L{-z2} , where z is the dynamical exponent of the biased single-particle Sinai walk. Typical stationary states are phase separated: At the largest barrier almost all particles queue at one side and almost all holes are at the other side. The high-density (low density) region is divided into approximately L{1/2} connected parts of particles (holes) which are separated by islands of holes (particles) located at the subleading barriers (valleys). We also study nonstationary processes of the system, like coarsening and invasion. Finally we discuss some related models, where particles of larger size or multiple occupation of lattice sites is considered. PMID- 17280033 TI - Monomer-dimer model in two-dimensional rectangular lattices with fixed dimer density. AB - The classical monomer-dimer model in two-dimensional lattices has been shown to belong to the "#P-complete" class, which indicates the problem is computationally "intractable." We use exact computational method to investigate the number of ways to arrange dimers on mxn two-dimensional rectangular lattice strips with fixed dimer density rho . For any dimer density 0 or =(d+2)(1-S{0})2;{d+1} , where S{0}[0,1] is the structure factor at k=0 (i.e., infinite-wavelength number variance) in the high-dimensional limit. We demonstrate that a Palasti-type conjecture (the saturation density in R{d} is equal to that of the one-dimensional problem raised to the d th power) cannot be true for RSA hyperspheres. We show that the structure factor S(k) must be analytic at k=0 and that RSA packings for 1< or =d< or =6 are nearly "hyperuniform." Consistent with the recent "decorrelation principle," we find that pair correlations markedly diminish as the space dimension increases up to six. We also obtain kissing (contact) number statistics for saturated RSA configurations on the surface of a d -dimensional sphere for dimensions 2< or =d< or =5 and compare to the maximal kissing numbers in these dimensions. We determine the structure factor exactly for the related "ghost" RSA packing in R{d} and demonstrate that its distance from "hyperuniformity" increases as the space dimension increases, approaching a constant asymptotic value of 12 . Our work has implications for the possible existence of disordered classical ground states for some continuous potentials in sufficiently high dimensions. PMID- 17280064 TI - Stochastic dynamics of a rod bouncing upon a vibrating surface. AB - We describe the behavior of a rod bouncing upon a horizontal surface which is undergoing sinusoidal vertical vibration. The predictions of computer simulations are compared with experiments in which a stainless-steel rod bounces upon a metal coated glass surface. We find that, as the dimensionless acceleration parameter Gamma is increased appreciably above unity, the motion of a long rod passes from periodic or near-periodic motion into stochastic dynamics. Within this stochastic regime the statistics of the times between impacts follow distributions with tails of approximately Gaussian form while the probability distributions of the angles at impact have tails that are close to exponential. We determine the dependence of each distribution upon the length of the rod, upon frequency, and on Gamma. The statistics of the total energy and of the translational and rotational components each approximately follow a Boltzmann distribution in their tails, the translational and rotational energy components being strongly correlated. The time-averaged mean vertical translational energy is significantly larger than the mean rotational energy, and both are considerably larger than the energy associated with horizontal motion. PMID- 17280065 TI - Granular elasticity: general considerations and the stress dip in sand piles. AB - Granular materials are predominantly plastic, incrementally nonlinear, preparation-dependent, and anisotropic under shear. Nevertheless, their static stress distribution is well accounted for, in the whole range up to the point of failure, by a judiciously tailored isotropic nonanalytic elasticity theory termed granular elasticity. The first purpose of this paper is to carefully expound this view. Then granular elasticity is employed to consider the stress distribution in two-dimensional sand piles (or sand wedges). Starting from a uniform density, the pressure at the bottom of the pile is found to show a single central peak. It turns into a pressure dip, if some density inhomogeneity, with the center being less compact, is assumed. These two pressure distributions are remarkably similar to recent measurements, made in piles obtained, respectively, by rainlike pouring and funneling. In an accompanying paper, the stress distributions in silos and under point loads, calculated using the same method, are also found to agree with experiments. PMID- 17280066 TI - Granular elasticity: stress distributions in silos and under point loads. AB - An elastic-strain-stress relation, the result of granular elasticity as introduced in the preceding paper, is employed here to calculate the stress distribution (a) in cylindrical silos and (b) under point loads assuming uniform density. In silos, the ratio k{J} between the horizontal and vertical stress is found to be constant (as conjectured by Janssen) and given as k{J}=1-sin phi (with phi the Coulomb yield angle), in agreement with a construction industry standard usually referred to as the Jaky formula. Next, the stress distribution at the bottom of a granular layer exposed to a point force at its top is calculated. The results include both vertical and oblique point forces, which agree well with simulations and experiments using rainlike preparation. Moreover, the stress distribution of a sheared granular layer exposed to the same point force is calculated and again found in agreement with given data. PMID- 17280067 TI - Micrometer-sized particles in a two-dimensional self-assembly during drying of liquid film. AB - We computed the self-organization process of a monodisperse collection of spherical micrometer-sized particles trapped in a two-dimensional thin liquid film isothermally dried on a chemically inert substrate. The substrate is either flat or indented to create linear stripes on its surface. The numerical results are illustrated and discussed in the light of experimental ones obtained from the drying of a water-based suspension of diamond particles (d{50}=10 microm) on a glass substrate. The drying of the suspension on a flat substrate leads to the formation of linear patterns and small clusters of micrometer-sized particles distributed over the whole surface of the substrate, whereas the drying of the suspension on an indented substrate leads to the aggregation of the particles along one side of the stripe which has a higher roughness than the other side of the stripe. This is an easy experimental way to obtain colloidal self-organized patterns. PMID- 17280068 TI - Mechanism for clogging of microchannels. AB - We investigate clogging of microchannels at the single-pore level using microfluidic devices as model porous media. The process of clogging is studied at low volume fractions and high flow rates, a technologically important regime. We show that clogging is independent of particle flow rate and volume fraction, indicating that collective effects do not play an important role. Instead, the average number of particles that can pass through a pore before it clogs scales with the ratio of pore to particle size. We present a simple model that accounts for the data. PMID- 17280069 TI - Stratification of colloidal aggregation coupled with sedimentation. AB - One of the consequences of sedimentation in colloidal aggregation is the stratification of the system in the sense that, after a sufficiently long elapsed time, the large clusters lie preferentially at the bottom zones of the confinement prism, and the structural and dynamical quantities describing the aggregates depend on the depth at which they are measured. A few years ago a computer simulation using particles for colloidal aggregation coupled with sedimentation was proposed by the author [A. E. Gonzalez, Phys. Rev. Lett. 86, 1243 (2001)]. In that simulation, due to computational limitations, the mentioned quantities were averaged over all clusters in the prism, independently of the depth at which they were located, in order to have good statistics for the evaluation of the cluster fractal dimension and the cluster size distribution function. In this work we present a computer simulation using particles of colloidal aggregation coupled with sedimentation, for which the clusters in the simulation box represent those clusters inside a layer at a fixed depth and of arbitrary thickness in the prism. It would then be possible to compare the results with an eventual validation experiment, in which an aggregating sample is sipped out with a pipette at a fixed depth in the prism and subjected to further studies, or with a light scattering study in which the laser beam is focused at a fixed depth in the system. We confirm the acceleration of the aggregation rate, followed by a slowing down, compared with an aggregating system driven purely by diffusion (DLCA). In the present system, the large clusters when drifting downwards sweep smaller ones, which in turn occlude the holes and cavities of these large clusters, increasing in this way their compacticity. We also confirm that (i) in some cases of sedimentation strengths and layer depths, the mean width (perpendicular to the gravitational field direction) and the mean height of the large settling clusters scale with the size as a power law, with the same scaling power, in some range of cluster sizes. This leads to self-similar clusters with an appreciably higher fractal dimension (d{f}) than the d{f} of DLCA clusters, a case that we called the "sweeping scaling regime" in earlier works. However, the present system is much richer than DLCA in that (ii) there are some other cases for which the parallel and perpendicular scaling powers differ, leading to anisotropic self-affine clusters. (iii) There are further cases for which only the mean width or the mean height scale as a power law, leading again to anisotropic clusters. Finally, (iv) there are still some cases for which neither the mean width nor mean height scale as a power law with the size. In the last (ii), (iii), and (iv) cases the large settling clusters are anisotropic and non-self-similar, and a fractal dimension cannot be defined for them, as found recently by some other authors for case (iii); however, their "compacticity" should be greater than that for DLCA clusters, in a yet undefined way. PMID- 17280070 TI - Observation of exchange of micropore water in cement pastes by two-dimensional T(2)-T(2) nuclear magnetic resonance relaxometry. AB - The first detailed analysis of the two-dimensional (2D) NMR T(2)-T(2) exchange experiment with a period of magnetization storage between the two T(2) relaxation encoding periods (T(2)-store-T(2)) is presented. It is shown that this experiment has certain advantages over the T(1)-T(2) variant for the quantization of chemical exchange. New T(2)-store-T(2) 2D 1H NMR spectra of the pore water within white cement paste are presented. Based on these spectra, the exchange rate of water between the two smallest porosity reservoirs is estimated for the first time. It is found to be of the order of 5 ms{-1}. Further, a careful estimate of the pore sizes of these reservoirs is made. They are found to be of the order of 1.4 nm and 10-30 nm , respectively. A discussion of the results is developed in terms of possible calcium silicate hydrate products. A water diffusion coefficient inferred from the exchange rate and the cement particle size is found to compare favorably with the results of molecular-dynamics simulations to be found in the literature. PMID- 17280071 TI - Non-Gaussian effects, space-time decoupling, and mobility bifurcation in glassy hard-sphere fluids and suspensions. AB - Brownian trajectory simulation methods are employed to fully establish the non Gaussian fluctuation effects predicted by our nonlinear Langevin equation theory of single particle activated dynamics in glassy hard-sphere fluids. The consequences of stochastic mobility fluctuations associated with the space-time complexities of the transient localization and barrier hopping processes have been determined. The incoherent dynamic structure factor was computed for a range of wave vectors and becomes of an increasingly non-Gaussian form for volume fractions beyond the (naive) ideal mode coupling theory (MCT) transition. The non Gaussian parameter (NGP) amplitude increases markedly with volume fraction and is well described by a power law in the maximum restoring force of the nonequilibrium free energy profile. The time scale associated with the NGP peak becomes much smaller than the alpha relaxation time for systems characterized by significant entropic barriers. An alternate non-Gaussian parameter that probes the long time alpha relaxation process displays a different shape, peak intensity, and time scale of its maximum. However, a strong correspondence between the classic and alternate NGP amplitudes is predicted which suggests a deep connection between the early and final stages of cage escape. Strong space time decoupling emerges at high volume fractions as indicated by a nondiffusive wave vector dependence of the relaxation time and growth of the translation relaxation decoupling parameter. Displacement distributions exhibit non-Gaussian behavior at intermediate times, evolving into a strongly bimodal form with slow and fast subpopulations at high volume fractions. Qualitative and semiquantitative comparisons of the theoretical results with colloid experiments, ideal MCT, and multiple simulation studies are presented. PMID- 17280072 TI - Interfacial states and far-from-equilibrium transitions in the epitaxial growth and erosion on (110) crystal surfaces. AB - We discuss the far-from-equilibrium interfacial phenomena occurring in the multilayer homoepitaxial growth and erosion on (110) crystal surfaces. Experimentally, these rectangular symmetry surfaces exhibit a multitude of interesting nonequilibrium interfacial structures, such as the rippled one dimensional periodic states that are not present in the homoepitaxial growth and erosion on the high symmetry (100) and (111) crystal surfaces. Within a unified phenomenological model, we reveal and elucidate this multitude of states on (110) surfaces as well as the transitions between them. By analytic arguments and numerical simulations, we address experimentally observed transitions between two types of rippled states on (110) surfaces. We discuss several intermediary interface states intervening, via consecutive transitions, between the two rippled states. One of them is the rhomboidal pyramid state, theoretically predicted by Golubovic [Phys. Rev. Lett. 89, 266104 (2002)] and subsequently seen, by de Mongeot and co-workers, in the epitaxial erosion of Cu(110) and Rh(110) surfaces [A. Molle, Phys. Rev. Lett. 93, 256103 (2004), and A. Molle, Phys. Rev. B 73, 155418 (2006)]. In addition, we find a number of interesting intermediary states having structural properties somewhere between those of rippled and pyramidal states. Prominent among them are the rectangular rippled states of long rooflike objects (huts) recently seen on Ag(110) surface. We also predict the existence of a striking interfacial structure that carries nonzero, persistent surface currents. Periodic surface currents vortex lattice formed in this so-called buckled rippled interface state is a far-from-equilibrium relative of the self-organized convective flow patterns in hydrodynamic systems. We discuss the coarsening growth of the multitude of the interfacial states on (110) crystal surfaces. PMID- 17280073 TI - Intrinsically anomalous roughness of randomly crumpled thin sheets. AB - We study the effect of folding ridges on the scaling properties of randomly crumpled sheets of different kinds of paper in the folded and unfolded states. We found that the mean ridge length scales with the sheet size with the scaling exponent mu determined by the competition between bending and stretching deformations in the folded sheet. This scaling determines the mass fractal dimension of randomly folded balls D{M}=2/mu. We also found that surfaces of crumpled balls, as well as unfolded sheets, both display self-affine invariance with zeta=nu{ph}, if mu < or =nu{ph} , where nu{ph}=34 is the size exponent for crumpled phantom membrane, or both exhibit an intrinsically anomalous roughness characterized by the universal local roughness exponent zeta=0.72+/-0.04 and the material dependent global roughness exponent alpha=mu, when mu>nu{ph}. The physical implications of these findings are discussed. PMID- 17280074 TI - Self-assembled treelike patterns from an evaporating binary solution. AB - Spontaneous formation of treelike patterns which developed during evaporation of the solvent from a phase-separated bilayer resulting from a binary polymer solution spin-coated onto a solid substrate has been studied. The initial bilayer consists of a poly(isobutyl methacrylate) (BMA) layer on top of a nitrocellulose (NC) solution layer. During evaporation, the top BMA layer becomes unstable and transforms into short ridges. Finally, the inhomogeneous evaporation of the solvent from the NC solution layer connects the BMA ridges to treelike patterns. To support our model, we present results of a complementary experiment based on casting of the BMA solution on an inclined glass substrate. PMID- 17280075 TI - Symmetry-based determination of space-time functions in nonequilibrium growth processes. AB - We study the space-time correlation and response functions in nonequilibrium growth processes described by linear stochastic Langevin equations. Exploiting exclusively the existence of space- and time-dependent symmetries of the noiseless part of these equations, we derive expressions for the universal scaling functions of two-time quantities which are found to agree with the exact expressions obtained from the stochastic equations of motion. The usefulness of the space-time functions is illustrated through the investigation of two atomistic growth models, the Family model and the restricted Family model, which are shown to belong to a unique universality class in 1+1 and 2+1 space dimensions. This corrects earlier studies which claimed that in 2+1 dimensions the two models belong to different universality classes. PMID- 17280076 TI - Computer simulations of two-dimensional and three-dimensional ideal grain growth. AB - We developed an efficient computation scheme for the phase-field simulation of grain growth, which allows unlimited number of the orientation variables and high computational efficiency independent of them. Large-scale phase-field simulations of the ideal grain growth in two-dimensions (2D) and three-dimensions (3D) were carried out with holding the coalescence-free condition, where a few tens of thousands grains evolved into a few thousand grains. By checking the validity of the von Neumann-Mullins law for individual grains, it could be shown that the present simulations were correctly carried out under the conditions of the ideal grain growth. The steady-state grain size distribution in 2D appeared as a symmetrical shape with a plateau slightly inclined to the small grain side, which was quite different from the Hillert 2D distribution. The existence of the plateau stems from the wide separation of the peaks in the size distributions of the grains with five, six, and seven sides. The steady-state grain size distribution in 3D simulation of the ideal grain growth appeared to be very close to the Hillert 3D distribution, independent of the initial average grain size and size distribution. The mean-field assumption, the Lifshitz-Slyozov stability condition, and all resulting predictions in the Hillert 3D theory were in excellent agreement with the present 3D simulation. Thus the Hillert theory can be regarded as an accurate description for the 3D ideal grain growth. The dependence of the growth rate in 3D simulations on the grain topology were discussed. The large-scale phase-field simulation confirms the 3D growth law obtained from the Surface Evolver simulations in smaller scales. PMID- 17280077 TI - Electrostatic potential and double layer force in a semiconductor-electrolyte semiconductor heterojunction. AB - This paper reports a theoretical study of the electrostatic potential within a so called pen-heterojunction made up of two semi-infinite, doped semiconductor media separated by an electrolyte region. An external potential is then applied across the entire system. Both the electrostatic potentials and double layer surface forces are studied as functions of the usual double layer system properties, semiconductor properties such as doping concentrations of acceptor and donator atoms, as well as applied potential. We find that both attractive and repulsive forces are possible depending on the surface charges on the electrolyte semiconductor interfaces, and that these forces can be significantly modified by the applied potential and by the doping levels in the semiconductors. PMID- 17280078 TI - Simulation and visualization of topological defects in nematic liquid crystals. AB - We present a method of visualizing topological defects arising in numerical simulations of liquid crystals. The method is based on scientific visualization techniques developed to visualize second-rank tensor fields, yielding information not only on the local structure of the field but also on the continuity of these structures. We show how these techniques can be used to first locate topological defects in fluid simulations of nematic liquid crystals where the locations are not known a priori and then study the properties of these defects including the core structure. We apply these techniques to simulation data obtained by previous authors who studied a rapid quench and subsequent equilibration of a Gay-Berne nematic. The quench produces a large number of disclination loops which we locate and track with the visualization methods. We show that the cores of the disclination lines have a biaxial region and the loops themselves are of a hybrid wedge-twist variety. PMID- 17280079 TI - Influence of flexibility on the biaxial nematic phase of bent core liquid crystals: a Monte Carlo simulation study. AB - The influence of flexibility on the phase behavior of bent core biaxial nematic liquid crystals is investigated using Monte Carlo simulation. A generic model for rigid V-shaped molecules is extended to include a bending potential, which allows us to investigate the relationship between the flexibility of a bent core molecule and its ability to form a biaxial nematic phase. The simulation results indicate that, as the flexibility is increased, the biaxial nematic phase is typically forced to lower temperatures. In contrast, the stability of the uniaxial nematic phase with respect to the isotropic phase is not significantly affected. The Landau point is split into a line of first order phase transitions between two different uniaxial phases. In some cases, the uniaxial nematic to biaxial nematic transition becomes first order, and a shape change is observed at this transition. PMID- 17280080 TI - Elastic actions exchanged by eccentric cylinders in liquid crystals. AB - Equilibria of a nematic liquid crystal confined between two eccentric cylinders are studied within a purely director approach. A planar equilibrium configuration competes against a three-dimensional one. A stability diagram is obtained in terms of both the ratio between the radii of the bounding cylinders and the distance between their axes. It turns out that the nonplanar minimizer has a structure more complex than that envisaged in the tensorial approach employed by McKay and Virga [Phys. Rev. E 71, 041702 (2005)] and that the planar configuration cannot be the absolute minimizer when the outer cylinder becomes a plane wall. The mechanical actions transmitted by the nematic liquid crystal on both bounding cylinders are computed and compared with other results available in the literature. PMID- 17280081 TI - Deuterium nuclear-magnetic-resonance study of a chiral smectic-C{*} phase. AB - This study reports deuterium nuclear-magnetic-resonance (NMR) spectra collected at 61.4MHz in the chiral smectic- C phase of liquid crystal 4{'}(octyloxy)-d{17} biphenyl-4- yl2 -chloro-3-methylpentanoate (BP8Cl). By using a goniometer probe, the oriented sample was rotated to collect spectra at different rotation (theta) angles. These spectra were simulated to gain information on solitonlike distortions in the helical superstructure. The Landau theory was adopted to study the distortion of the helix by the NMR magnetic field. Deuterium two-dimensional exchange experiments were also used on the aligned sample at theta=15 degrees to obtain dynamic parameters through the spectral simulation. The interlayer diffusion constants in the SmC{*} phase were estimated from a proton T(1) dispersion study. The pitch length of BP8Cl is estimated to be circa 2-3 microns at one temperature. PMID- 17280082 TI - Enhanced photonic band edge laser emission in a cholesteric liquid crystal resonator. AB - A highly efficient photonic band edge dye-doped cholesteric liquid crystal (CLC) laser is demonstrated. By sandwiching an active CLC cell within a resonator consisting of two passive CLC reflectors, the lasing efficiency is dramatically enhanced. Theoretical analysis using the improved 4x4 transfer matrix and scattering matrix shows that the band edge laser mode can be supported by the external CLC resonator and its optimal output can be achieved by a relatively thin active CLC layer and thin passive CLC reflectors. Theoretical analysis agrees well with the experimental results. PMID- 17280083 TI - Stabilizing the blue phases. AB - We present an investigation of the phase diagram of cholesteric liquid crystals within the framework of Landau-de Gennes theory. The free energy is modified to incorporate all three Frank elastic constants and to allow for a temperature dependent pitch in the cholesteric phase. It is found that the region of stability of the cubic blue phases depends significantly on the value of the elastic constants, being reduced when the bend elastic constant is larger than splay and when twist is smaller than the other two. Most dramatically we find a large increase in the region of stability of blue phase I, and a qualitative change in the phase diagram, in a system where the cholesteric phase displays helix inversion. PMID- 17280084 TI - Electroclinic effect in a chiral smectic-A liquid crystal stabilized by an anisotropic polymer network. AB - We have studied the effect of an anisotropic polymer network on the coupling of molecular tilt to applied electric field in the chiral S{A} phase. The polymer network is formed from a photoreactive achiral monomer in a thin planar S{C}{*} cell. Experimental data, obtained from electro-optical measurements near to the S{A}-S{c}{*} transition temperature, T{c} , of the induced molecular tilt, switching time, as well as induced polarization as a function of temperature and electric field strength are presented. The results clearly show that, close to T{c} , the electroclinic effect is largely controlled by the polymer network. The experimental results are discussed in the framework of a simple phenomenological model, extended from the Landau model, which includes the bulk free energy arising from the anisotropic interaction between the polymer network and the liquid crystal director, and the elastic free energy resulting from the anchoring (supposed rigid) of the liquid crystal molecules at the polymer boundaries. PMID- 17280085 TI - Lattice Boltzmann scheme for modeling liquid-crystal dynamics: Zenithal bistable device in the presence of defect motion. AB - A lattice Boltzmann scheme is presented which recovers the dynamics of nematic and chiral liquid crystals; the method essentially gives solutions to the Qian Sheng [Phys. Rev. E 58, 7475 (1998)] equations for the evolution of the velocity and tensor order-parameter fields. The resulting algorithm is able to include five independent Leslie viscosities, a Landau-deGennes free energy which introduces three or more elastic constants, a temperature dependent order parameter, surface anchoring and viscosity coefficients, flexoelectric and order electricity, and chirality. When combined with a solver for the Maxwell equations associated with the electric field, the algorithm is able to provide a full "device solver" for a liquid crystal display. Coupled lattice Boltzmann schemes are used to capture the evolution of the fast momentum and slow director motions in a computationally efficient way. The method is shown to give results in close agreement with analytical results for a number of validating examples. The use of the method is illustrated through the simulation of the motion of defects in a zenithal bistable liquid crystal device. PMID- 17280086 TI - Correlations between the performance characteristics of a liquid crystal laser and the macroscopic material properties. AB - In order to understand how the performance of a liquid-crystal laser depends on the physical properties of the low molar mass nematic host, we have studied the energy threshold and slope efficiency of ten optically pumped liquid-crystal lasers based on different hosts. Specifically, this leads to a variation in the birefringence, the orientational order parameter, and the order parameter of the transition dipole moment of the dye. It is found that low threshold energies and high slope efficiencies correlate with high order parameters and large birefringences. To a first approximation this can be understood by considering analytical expressions for the threshold and slope efficiency, which are derived from the space-independent rate equations for a two-level system, in terms of the macroscopic liquid crystal properties. PMID- 17280087 TI - Crossover from reptation to Rouse dynamics in the cage model. AB - The two-dimensional cage model for polymer motion is discussed with an emphasis on the effect of sideways motions, which cross the barriers imposed by the lattice. Using the density matrix method as a solver of the master equation, the renewal time and the diffusion coefficient are calculated as a function of the strength of the barrier crossings. A strong crossover influence of the barrier crossings is found and it is analyzed in terms of effective exponents for a given chain length. The crossover scaling functions and the crossover scaling exponents are calculated. PMID- 17280088 TI - Nonlocal model for nematic liquid-crystal elastomers. AB - We have developed a fully nonlocal model to describe the dynamic behavior of nematic liquid-crystal elastomers. The free energy, incorporating both elastic and nematic contributions, is a function of the material displacement vector and the orientational order parameter tensor. The free energy cost of spatial variations of these order parameters is taken into account through nonlocal interactions rather than through the use of gradient expansions. We also give an expression for the Rayleigh dissipation function. The equations of motion for displacement and orientational order are obtained from the free energy and the dissipation function by the use of a Lagrangian approach. We examine the free energy and the equations of motion in the limit of long-wavelength and small amplitude variations of the displacement and the orientational order parameter. We compare our results with those in the literature. If the scalar order parameter is held fixed, we recover the usual viscoelastic theory for nematic liquid crystals. PMID- 17280089 TI - Glass transition of polymers: atomistic simulation versus experiments. AB - With experimental investigations and current theories, molecular modeling became an inevitable technique to study the perplexing phenomenon of glass transition. Among polymers, small variations in atomic interactions yield different values of the glass transition temperature, T{g}. To reveal the influence of differences in the atomic functionality on the value of T{g}, and thus to probe the molecular mechanisms responsible for this transition, atomistic simulations have to be undertaken. However, such simulations are argued not to accurately represent physically the glass transition due to the long relaxation times involved. Here we show the universality of the well-known Williams-Landel-Ferry equation for the experimental thermal dependence of polymer viscosities as demonstrated with atomistic simulations. Consequently, atomic aspects could be explicitly revealed. The contribution of atomistic simulation to the study of glass transition is thus confirmed. However, it has to be used complementarily with experiments and coarse grained simulation to reveal the atomic aspects of current theories. PMID- 17280090 TI - Equilibration of experimentally determined protein structures for molecular dynamics simulation. AB - Preceding molecular dynamics simulations of biomolecular interactions, the molecule of interest is often equilibrated with respect to an initial configuration. This so-called equilibration stage is required because the input structure is typically not within the equilibrium phase space of the simulation conditions, particularly in systems as complex as proteins, which can lead to artifactual trajectories of protein dynamics. The time at which nonequilibrium effects from the initial configuration are minimized-what we will call the equilibration time-marks the beginning of equilibrium phase-space exploration. Note that the identification of this time does not imply exploration of the entire equilibrium phase space. We have found that current equilibration methodologies contain ambiguities that lead to uncertainty in determining the end of the equilibration stage of the trajectory. This results in equilibration times that are either too long, resulting in wasted computational resources, or too short, resulting in the simulation of molecular trajectories that do not accurately represent the physical system. We outline and demonstrate a protocol for identifying the equilibration time that is based on the physical model of Normal Mode Analysis. We attain the computational efficiency required of large protein simulations via a stretched exponential approximation that enables an analytically tractable and physically meaningful form of the root-mean-square deviation of atoms comprising the protein. We find that the fitting parameters (which correspond to physical properties of the protein) fluctuate initially but then stabilize for increased simulation time, independently of the simulation duration or sampling frequency. We define the end of the equilibration stage--and thus the equilibration time--as the point in the simulation when these parameters attain constant values. Compared to existing methods, our approach provides the objective identification of the time at which the simulated biomolecule has entered an energetic basin. For the representative protein considered, bovine pancreatic trypsin inhibitor, existing methods indicate a range of 0.2-10 ns of simulation until a local minimum is attained. Our approach identifies a substantially narrower range of 4.5-5.5 ns , which will lead to a much more objective choice of equilibration time. PMID- 17280092 TI - Nonperturbative retrieval of the scattering strength in one-dimensional media. AB - We examine several approaches on how to use the transmission and reflection amplitudes as functions of the modulation frequency of the laser's intensity to reconstruct the position-dependent scattering coefficient for a simple turbid medium. We explore the region where the contrast between the coefficient and its spatially averaged value is large enough such that perturbative methods fail. We show that in the case of a transillumination geometry, the knowledge of the transmission profile alone is not sufficient for unique image reconstruction, whereas the reflection spectrum allows for a complete inversion. We demonstrate the invertibility for media sampled at only a few positions. PMID- 17280091 TI - Transition from long- to short-lived transient pores in giant vesicles in an aqueous medium. AB - We have observed large pores in the membrane of giant vesicles in an aqueous medium. The lifetime of the pores can reach 2 min and their size (a few micrometers) enables their visualization by fluorescence microscopy. These pores are obtained thanks to a destabilization of the membrane due to the synergistic action of a cone-shaped and nitrobenzodiazole (NBD) labeled phospholipid illuminated in the presence of dithionite. The opening of the pore occurs immediately after illumination starts so that it can be accurately triggered. A concomitant decrease of the vesicle radius is observed; we interpret it as a solubilization of the membrane. Depending on the rate of this solubilization, long- or short-lived pores were observed. At the transition between both regimes for a 30 microm vesicle, the solubilization rate was about 1/300 s{-1} . In order to interpret these observations, we have revisited the current model of pore opening to take into account this solubilization. This proposed model along with simulations enables us to prove that solubilization explains why the large long lived pores are observed even in an aqueous medium. The model also predicts the solubilization rate at the transition between a single long-lived pore and a cascade of short-lived pores. PMID- 17280093 TI - Dynamics of spiral pairs induced by unidirectional propagating pulses. AB - The dynamics of unidirectionally propagating pulses in a two-dimensional uniform excitable reaction-diffusion medium is investigated. It is shown that under weak diffusion coupling between medium points such a pulse can evolve into a pair of counter-rotating spirals (spiral pair). We analyze the drift of such a pair and examine the collisions between several drifting pairs. It is demonstrated that collisions can result in a special type of reflection or, alternatively, in new types of complex stationary spiral structures. A possible application of these findings for the diagnosis of cardiac arrhythmias is suggested. PMID- 17280094 TI - Calcium dynamics on a stochastic reaction-diffusion lattice model. AB - We study a stochastic reaction-diffusion lattice model for describing the calcium dynamics in the endoplasmic reticulum (ER) membrane. Calcium channels and calcium ions are placed in two interpenetrating square lattices which are connected by calcium release and diffusion. Calcium ions are released from the ER through the channels and they can both remain in the membrane or spontaneously leave the membrane into the cytosol. The state of the channel is modulated by calcium ions: a channel can be open, closed, or inactive. The model is studied by numerical simulations and mean field theory and exhibits a phase transition from an active state to an absorbing state which is the result of the catalytic calcium release. The critical behavior of the model is in the directed percolation universality class. PMID- 17280095 TI - Periodicity and chaos in electrically coupled Hindmarsh-Rose neurons. AB - The Hindmarsh-Rose (HR) system of equations is a model that captures the essential of the spiking activity of biological neurons. In this work we present an exploratory numerical study of the time activities of two HR neurons interacting through electrical synapses. The knowledge of this simple system is a first step towards the understanding of the cooperative behavior of large neural assemblies. Several periodic and chaotic attractors where identified, as the coupling strength is increased from zero until the perfect synchronization regime. In addition to the known phase locking synchronization at weak coupling, electrical synapses also allow for both in-phase and antiphase synchronization from moderate to strong coupling. A regime where the system changes apparently randomly between in-phase and antiphase locking evolves to a bistability regime, where both in-phase and antiphase periodic attractors are locally stable. At the strong coupling regime in-phase chaotic evolution dominates, but windows with complex periodic behavior are also present. PMID- 17280096 TI - Effect of supercoiling on formation of protein-mediated DNA loops. AB - DNA loop formation is one of several mechanisms used by organisms to regulate genes. The free energy of forming a loop is an important factor in determining whether the associated gene is switched on or off. In this paper we use an elastic rod model of DNA to determine the free energy of forming short (50-100 basepair), protein mediated DNA loops. Superhelical stress in the DNA of living cells is a critical factor determining the energetics of loop formation, and we explicitly account for it in our calculations. The repressor protein itself is regarded as a rigid coupler; its geometry enters the problem through the boundary conditions it applies on the DNA. We show that a theory with these ingredients is sufficient to explain certain features observed in modulation of in vivo gene activity as a function of the distance between operator sites for the lac repressor. We also use our theory to make quantitative predictions for the dependence of looping on superhelical stress, which may be testable both in vivo and in single-molecule experiments such as the tethered particle assay and the magnetic bead assay. PMID- 17280097 TI - Phase transition in the collective migration of tissue cells: experiment and model. AB - We have recorded the swarming-like collective migration of a large number of keratocytes (tissue cells obtained from the scales of goldfish) using long-term videomicroscopy. By increasing the overall density of the migrating cells, we have been able to demonstrate experimentally a kinetic phase transition from a disordered into an ordered state. Near the critical density a complex picture emerges with interacting clusters of cells moving in groups. Motivated by these experiments we have constructed a flocking model that exhibits a continuous transition to the ordered phase, while assuming only short-range interactions and no explicit information about the knowledge of the directions of motion of neighbors. Placing cells in microfabricated arenas we found spectacular whirling behavior which we could also reproduce in simulations. PMID- 17280098 TI - Light scattering regimes along the optical axis in turbid media. AB - We inject an angularly collimated laser beam into a scattering medium of a nondairy creamer-water solution and examine the distribution of the scattered light along the optical axis as a function of the source-detector spacing. The experimental and simulated data obtained from a Monte Carlo simulation suggest four regimes characterizing the transition from unscattered to diffusive light. We compare the data also with theoretical predictions based on a first-order scattering theory for regions close to the source, and with diffusionlike theories for larger source-detector spacings. We demonstrate the impact of the measurement process and the effect of the unavoidable absorption of photons by the detection fiber on the light distribution inside the medium. We show that the range of validity of these theories can depend on the experimental parameters such as the diameter and acceptance angle of the detection fiber. PMID- 17280099 TI - Episodic synchronization in dynamically driven neurons. AB - We examine the response of type II excitable neurons to trains of synaptic pulses, as a function of the pulse frequency and amplitude. Similarly to the case of harmonic inputs, these neurons exhibit a resonant behavior also for pulsed inputs. We interpret this phenomenon in terms of the subthreshold response of the neuron. In the presence of dynamical trains of input pulses whose frequency varies continuously in time, the receiving neuron synchronizes episodically to the input pulses, whenever the pulse frequency lies within the neuron's locking range. The results are obtained both in numerical simulations of the Morris-Lecar model and in an electronic implementation of the FitzHugh-Nagumo system, evidencing the robustness of the phenomenon. PMID- 17280100 TI - Protein fluctuations and breakdown of time-scale separation in rate theories. AB - A long-time fluctuation correlation function with a power-law form has been observed in recent single-molecule experiments by the Xie group. By analyzing the dynamics of an elastic network model (ENM) under white noise, we show that the observed long-time memory kernel can be explained by the discrepancy between the experimentally measured coordinate (or the coordinate directly coupled to protein function) and the minimum energy path of the system. Consequently, the dynamics of the measured collective coordinate has contributions from degrees of freedoms with a broad distribution of time scales. Our study also implies that the widely used ENM Hamiltonian should be viewed as a coarse-grained model of a protein over a rugged energy landscape. Large effective drag coefficients are needed to describe protein dynamics with the ENM's. PMID- 17280101 TI - Internal protein dynamics shifts the distance to the mechanical transition state. AB - Mechanical unfolding of polyproteins by force spectroscopy provides valuable insight into their free energy landscapes. Most experiments of the unfolding process have been fit to two-state and/or one dimensional models, with the details of the protein and its dynamics often subsumed into a zero-force unfolding rate and a distance x{u}{1D} to the transition state. We consider the entire phase space of a model protein under a constant force, and show that x{u}{1D} contains a sizeable contribution from exploring the full multidimensional energy landscape. This effect is greater for proteins with many degrees of freedom that are affected by force; and surprisingly, we predict that externally attached flexible linkers also contribute to the measured unfolding characteristics. PMID- 17280102 TI - Hydrodynamics of isotropic and liquid crystalline active polymer solutions. AB - We describe the large-scale collective behavior of solutions of polar biofilaments and stationary and mobile crosslinkers. Both mobile and stationary crosslinkers induce filament alignment promoting either polar or nematic order. In addition, mobile crosslinkers, such as clusters of motor proteins, exchange forces and torques among the filaments and render the homogeneous states unstable via filament bundling. We start from a Smoluchowski equation for rigid filaments in solutions, where pairwise crosslink-mediated interactions among the filaments yield translational and rotational currents. The large-scale properties of the system are described in terms of continuum equations for filament and motor densities, polarization, and alignment tensor obtained by coarse-graining the Smoluchovski equation. The possible homogeneous and inhomogeneous states of the systems are obtained as stable solutions of the dynamical equations and are characterized in terms of experimentally accessible parameters. We make contact with work by other authors and show that our model allows for an estimate of the various parameters in the hydrodynamic equations in terms of physical properties of the crosslinkers. PMID- 17280103 TI - How to determine local elastic properties of lipid bilayer membranes from atomic force-microscope measurements: a theoretical analysis. AB - Measurements with an atomic force microscope (AFM) offer a direct way to probe elastic properties of lipid bilayer membranes locally: provided the underlying stress-strain relation is known, material parameters such as surface tension or bending rigidity may be deduced. In a recent experiment a pore-spanning membrane was poked with an AFM tip, yielding a linear behavior of the force-indentation curves. A theoretical model for this case is presented here which describes these curves in the framework of Helfrich theory. The linear behavior of the measurements is reproduced if one neglects the influence of adhesion between tip and membrane. Including it via an adhesion balance changes the situation significantly: force-distance curves cease to be linear, hysteresis and nonzero detachment forces can show up. The characteristics of this rich scenario are discussed in detail in this paper. PMID- 17280105 TI - Tight coupling in thermal Brownian motors. AB - We study analytically a thermal Brownian motor model and calculate exactly the Onsager coefficients. We show how the reciprocity relation holds and that the determinant of the Onsager matrix vanishes. Such a condition implies that the device is built with tight coupling. This explains why Carnot's efficiency can be achieved in the limit of infinitely slow velocities. We also prove that the efficiency at maximum power has the maximum possible value, which corresponds to the Curzon-Alhborn bound. Finally, we discuss the model acting as a Brownian refrigerator. PMID- 17280104 TI - Dimensional crossover of heat conduction in low dimensions. AB - The dimensional crossover phenomena of heat conduction is studied by a two dimensional (2D) Fermi-Pasta-Ulam lattice. The 2D divergence law of the thermal conductivity is confirmed by the simulations results. The divergence law of the thermal conductivity will change from the 2D class to 1D class as delta=N{y}N{x} decreases, here N{y} is the size in transverse direction and Nx in longitude direction. The simulation's results suggest that the dimensional crossover happens in delta{*}-->0 as N{x}-->infinity . PMID- 17280106 TI - Square-well fluids in confined space with discretely attractive wall-fluid potentials: critical point shift. AB - In this work the effects of the wall-fluid interaction on the critical point shift are studied by using a discrete and attractive wall-fluid interaction and density functional theory. In contrast to the previous assumption, it is found that the dependence of critical temperature shift on the wall-fluid interaction does not simply show a monotonic manner, but increases with the strength of the interaction for weak surfaces, then decreases for strong surfaces. The similar trend holds for the systems with different fluid-fluid interactions and different confined spaces. Unlike the capillary critical temperature, the critical density of square-well fluids in a confined space increases monotonically as the wall fluid interaction becomes more attractive. PMID- 17280107 TI - Nonlinear refractive index measurements of discotic and calamitic nematic lyotropic phases. AB - In this work, through the Z-scan technique, we report on measurements of the nonlinear refractive index (n{2}) in discotic and calamitic nematic phases at room temperature in lyotropic mixtures of potassium laurate, decanol and D(2)O . This technique presents high sensitivity when compared to conventional interferometry. The nonlinear optical birefringence (Deltan{2}) of these nematic phases was also determined. The sign and absolute value of this relevant nonlinear parameter are discussed in terms of structural changes in the micellar configuration which takes place in each nematic lyotropic phase. PMID- 17280108 TI - Comment on "Heat fluctuations in Brownian transducers". AB - The results presented in [A. Gomez-Marin and J.M. Sancho, Phys. Rev. E 73, 045101(R) (2006)] are mathematically incomplete and physically faulty. Contrary to their claim, there exists a fluctuation theorem for the heat probability distribution function in Brownian transducers operating between two heat reservoirs. The corresponding large deviation function is determined exactly. PMID- 17280110 TI - Collisions of pulses can lead to holes via front interaction in the cubic-quintic complex Ginzburg-Landau equation in an annular geometry. AB - We study the interaction of counterpropagating pulse solutions for two coupled complex cubic-quintic Ginzburg-Landau equations in an annular geometry. For small approach velocity we find as an outcome of such collisions several results including zigzag bound pulses, stationary bound states of 2pi holes, zigzag 2pi holes, stationary bound states of pi holes, zigzag bound states of pi holes, propagating 2pi holes, and propagating pi holes as the real part of the cubic cross coupling between the counterpropagating waves is increased. We characterize in detail the collisions giving rise to the three states involving pi holes as an outcome. PMID- 17280111 TI - Shear driven solitary waves on a liquid film. AB - Long nonlinear two-dimensional traveling waves on a film driven by laminar gas flow are investigated numerically via solving Navier-Stokes equations. The evolution of their shape, amplitude, and speed with increasing Reynolds number is studied. The existence of solitary waves is demonstrated. A comparison between shear driven and gravity-capillary waves is made and discussed. It is shown that shear driven waves as compared to gravity driven waves are much higher for equal film Reynolds numbers and much slower for equal wave amplitudes. PMID- 17280112 TI - Relativistic plasma control for single attosecond x-ray burst generation. AB - We show that managing time-dependent polarization of the relativistically intense laser pulse incident on a plasma surface allows us to gate a single (sub)attosecond x-ray burst even when a multicycle driver is used. The single x ray burst is emitted when the tangential component of the vector potential at the plasma surface vanishes. This relativistic plasma control is based on the theory of relativistic spikes [T. Baeva, S. Gordienko, and A. Pukhov, Phys. Rev. E 74, 046404 (2006)]. The relativistic plasma control is demonstrated here numerically by particle-in-cell simulations. PMID- 17280113 TI - Formation and light guiding properties of dark solitons in one-dimensional waveguide arrays. AB - We report on the formation of dark discrete solitons in a nonlinear periodic system consisting of evanescently coupled channel waveguides in defocusing lithium niobate. Localized nonlinear dark modes displaying a phase jump in the center that is located either on-channel (mode A) or in-between channels (mode B) are formed, which is to our knowledge the first experimental observation of mode B. By numerical simulations we find that the saturable nature of the nonlinearity is responsible for the improved stability of mode B. The ability of the induced refractive index structures to guide light of a low-power probe beam is demonstrated. PMID- 17280114 TI - Inelastic scattering and interactions of three-wave parametric solitons. AB - We study the interactions of velocity-locked three-wave parametric solitons in a medium with quadratic nonlinearity and dispersion. We reveal that the inelastic scattering between three-wave solitons and linear waves may be described in terms of analytical solutions with dynamically varying group velocity, or boomerons. Moreover, we demonstrate the elastic nature of three-wave soliton-soliton collisions and interactions. PMID- 17280115 TI - Statistical mechanics of two hard spheres in a box. AB - We investigate some statistical mechanical properties of a system consisting of two hard spheres in a D-dimensional rectangular box (D=1, 2, ...). We give a theoretical method for computing a configurational partition function Zc,D of this system and compare the equation of state obtained from Zc,D with molecular dynamics simulations. Especially in D=3, we give a fully analytic expression for the pressure which turns out to have one or more negative compressibility regions when the box size is small. PMID- 17280116 TI - Networks with dispersed degrees save stable coexistence of species in cyclic competition. AB - Coexistence of individuals with different species or phenotypes is often found in nature in spite of competition between them. Stable coexistence of multiple types of individuals have implications for maintenance of ecological biodiversity and emergence of altruism in society, to name a few. Various mechanisms of coexistence including spatial structure of populations, heterogeneous individuals, and heterogeneous environments, have been proposed. In reality, individuals disperse and interact on complex networks. We examine how heterogeneous degree distributions of networks influence coexistence, focusing on models of cyclically competing species. We show analytically and numerically that heterogeneity in degree distributions promotes stable coexistence. PMID- 17280117 TI - Successive splitting of autowaves in a nonlinear chemical reaction medium. AB - The phenomenon of wave splitting is investigated in a two-dimensional excitable light-sensitive Belousov-Zhabotinsky reaction medium after extremely changing the intensity of illuminated light for a short time. It is found that successive wave splitting and nonannihilation collision between two waves of different amplitudes occur spontaneously under narrow experimental conditions. Experimental observations are approximately reproduced in the specific parameter range by a numerical simulation with a Bar-Eiswirth model. PMID- 17280118 TI - Oscillations of complex networks. AB - A complex network processing information or physical flows is usually characterized by a number of macroscopic quantities such as the diameter and the betweenness centrality. An issue of significant theoretical and practical interest is how such quantities respond to sudden changes caused by attacks or disturbances in recoverable networks, i.e., functions of the affected nodes are only temporarily disabled or partially limited. By introducing a model to address this issue, we find that, for a finite-capacity network, perturbations can cause the network to oscillate persistently in the sense that the characterizing quantities vary periodically or randomly with time. We provide a theoretical estimate of the critical capacity-parameter value for the onset of the network oscillation. The finding is expected to have broad implications as it suggests that complex networks may be structurally highly dynamic. PMID- 17280119 TI - Network models of phage-bacteria coevolution. AB - Bacteria and their bacteriophages are the most abundant, widespread, and diverse groups of biological entities on the planet. In an attempt to understand how the interactions between bacteria, virulent phages, and temperate phages might affect the diversity of these groups, we developed a stochastic network model for examining the coevolution of these ecologies. In our approach, nodes represent whole species or strains of bacteria or phages, rather than individuals, with "speciation" and extinction modeled by duplication and removal of nodes. Phage bacteria links represent host-parasite relationships and temperate-virulent phage links denote prophage-encoded resistance. The effect of horizontal transfer of genetic information between strains was also included in the dynamical rules. The observed networks evolved in a highly dynamic fashion but the ecosystems were prone to collapse (one or more entire groups going extinct). Diversity could be stably maintained in the model only if the probability of speciation was independent of the diversity. Such an effect could be achieved in real ecosystems if the speciation rate is primarily set by the availability of ecological niches. PMID- 17280120 TI - 1/f noise and avalanche scaling in plastic deformation. AB - We study the intermittency and noise of dislocation systems undergoing shear deformation. Simulations of a simple two-dimensional discrete dislocation dynamics model indicate that the deformation rate exhibits a power spectrum scaling of the type 1/falpha. The noise exponent is far away from a Lorentzian, with alpha approximately 1.5. This result is directly related to the way the durations of avalanches of plastic deformation activity scale with their size. PMID- 17280121 TI - Degree mixing and the enhancement of synchronization in complex weighted networks. AB - Real networks often consist of local units interacting with each other by means of heterogeneous connections. In many cases, furthermore, such networks feature degree mixing properties, i.e., the tendency of nodes with high degree (with low degree) to connect with connectivity peers (with highly connected nodes). Such degree-degree correlations may have an important influence in the spreading of information or infectious agents on a network. We explore the role played by these correlations for the synchronization of networks of coupled dynamical systems. Using a stochastic optimization technique, we find that the value of degree mixing providing optimal conditions for synchronization depends on the weighted coupling scheme. We also show that a minimization of the assortative coefficient may induce a strong destabilization of the synchronous state. We illustrate our findings for weighted networks with scale free and random topologies. PMID- 17280122 TI - Tomography of scale-free networks and shortest path trees. AB - In this paper we model the tomography of scale-free networks by studying the structure of layers around an arbitrary network node. We find, both analytically and empirically, that the distance distribution of all nodes from a specific network node consists of two regimes. The first is characterized by rapid growth, and the second decays exponentially. We also show analytically that the nodes degree distribution at each layer exhibits a power-law tail with an exponential cutoff. We obtain similar empirical results for the layers surrounding the root of shortest path trees cut from such networks, as well as the Internet. PMID- 17280123 TI - Transient and stationary behavior of the Olami-Feder-Christensen model. AB - Using long-term computer simulations and mean-field-like arguments, we investigate the transient time and the properties of the stationary state of the Olami-Feder-Christensen model as function of the coupling parameter alpha and the system size N. The most important findings are that the transient time increases with a nonuniversal exponent of the system size, and that the avalanche size distribution will not approach a power law with increasing system size. PMID- 17280124 TI - Dry friction avalanches: experiment and theory. AB - Experimental evidence and theoretical models are presented supporting the conjecture that dry friction stick-slip is described by self-organized criticality. We use the data, obtained with a pin-on-disk tribometer set to measure lateral force, to examine the variation of the friction force as a function of time. We study nominally flat surfaces of matching aluminum and steel. The probability distribution of force drops follows a negative power law with exponents mu in the range 3.2-3.5. The frequency power spectrum follows a 1/f alpha pattern with alpha in the range 1-1.8. We first compare these experimental results with the well-known Robin Hood model of self-organized criticality. We find good agreement between theory and experiment for the force drop distribution but not for the power spectrum. We explain this on a physical basis and propose a model which takes explicitly into account the stiffness and inertia of the tribometer. Specifically, we numerically solve the equation of motion of a block on a friction surface pulled by a spring and show that for certain spring constants the motion is characterized by the same power law spectrum as in experiments. We propose a physical picture relating the fluctuations of the force drops to the microscopic geometry of the surface. PMID- 17280125 TI - Cascade and breakdown in scale-free networks with community structure. AB - The cascade failures in scale-free networks with community structure are studied and cascade propagation of such networks with different modularity parameters is simulated. It is found that the network with small modularity is much easier to trigger cascade failures than that of the larger one. Furthermore, different removal strategies have some what large effects on the cascade failures aftereffect. The simulations also show that larger modularity and reserve capacity coefficient will delay the breakdown caused by a cascade of network. This is particularly important for such real networks with community as traffic networks, distribution networks, and electrical power grids. PMID- 17280126 TI - Fitness model for the Italian interbank money market. AB - We use the theory of complex networks in order to quantitatively characterize the formation of communities in a particular financial market. The system is composed by different banks exchanging on a daily basis loans and debts of liquidity. Through topological analysis and by means of a model of network growth we can determine the formation of different group of banks characterized by different business strategy. The model based on Pareto's law makes no use of growth or preferential attachment and it reproduces correctly all the various statistical properties of the system. We believe that this network modeling of the market could be an efficient way to evaluate the impact of different policies in the market of liquidity. PMID- 17280127 TI - Epidemic dynamics of two species of interacting particles on scale-free networks. AB - We study the nonequilibrium phase transition in a model for epidemic spreading on scale-free networks. The model consists of two particle species A and B, and the coupling between them is taken to be asymmetric; A induces B while B suppresses A. This model describes the spreading of an epidemic on networks equipped with a reactive immune system. We present analytic results on the phase diagram and the critical behavior, which depends on the degree exponent gamma of the underlying scale-free networks. Numerical simulation results that support the analytic results are also presented. PMID- 17280128 TI - Spreading dynamics on heterogeneous populations: multitype network approach. AB - I study the spreading of infectious diseases in heterogeneous populations. The population structure is described by a contact graph where vertices represent agents and edges represent disease transmission channels among them. The population heterogeneity is taken into account by the agent's subdivision in types and the mixing matrix among them. I introduce a type-network representation for the mixing matrix, allowing an intuitive understanding of the mixing patterns and the calculations. Using an iterative approach I obtain recursive equations for the probability distribution of the outbreak size as a function of time. I demonstrate that the expected outbreak size and its progression in time are determined by the largest eigenvalue of the reproductive number matrix and the characteristic distance between agents on the contact graph. Finally, I discuss the impact of intervention strategies to halt epidemic outbreaks. This work provides both a qualitative understanding and tools to obtain quantitative predictions for the spreading dynamics of heterogeneous populations. PMID- 17280129 TI - Strong effects of network architecture in the entrainment of coupled oscillator systems. AB - Random networks of coupled phase oscillators, representing an approximation for systems of coupled limit-cycle oscillators, are considered. Entrainment of such networks by periodic external forcing applied to a subset of their elements is numerically and analytically investigated. For a large class of interaction functions, we find that the entrainment window with a tongue shape becomes exponentially narrow for networks with higher hierarchical organization. However, the entrainment is significantly facilitated if the networks are directionally biased--i.e., closer to the feedforward networks. Furthermore, we show that the networks with high entrainment ability can be constructed by evolutionary optimization processes. The neural network structure of the master clock of the circadian rhythm in mammals is discussed from the viewpoint of our results. PMID- 17280130 TI - Statistical mechanics of scale-free networks at a critical point: complexity without irreversibility? AB - Based on a rigorous extension of classical statistical mechanics to networks, we study a specific microscopic network Hamiltonian. The form of this Hamiltonian is derived from the assumption that individual nodes increase or decrease their utility by linking to nodes with a higher or lower degree than their own. We interpret utility as an equivalent to energy in physical systems and discuss the temperature dependence of the emerging networks. We observe the existence of a critical temperature Tc where total energy (utility) and network architecture undergo radical changes. Along this topological transition we obtain ensemble averages of scale-free networks with complex hierarchical topology. The scale free nature emerges strictly within equilibrium, with a clearly defined microcanonical ensemble and the principle of detailed balance fulfilled. This provides evidence that "complex" networks may arise without irreversibility. The utility approach establishes a link between classical statistical physics and a wide variety of applications in socioeconomic statistical systems. PMID- 17280131 TI - Robust emergent activity in dynamical networks. AB - We study the evolution of a random weighted network with complex nonlinear dynamics at each node, whose activity may cease as a result of interactions with other nodes. Starting from a knowledge of the microlevel behavior at each node, we develop a macroscopic description of the system in terms of the statistical features of the subnetwork of active nodes. We find that very different networks evolve to active subnetworks with similar asymptotic characteristics: the size of the active set is independent of the total number of nodes in the network, and the average degree of the active nodes is independent of both the network size and its connectivity. This robustness has strong implications for dynamical networks observed in the natural world, notably the existence of a characteristic range of links per species across ecological systems. PMID- 17280132 TI - Kinetic equations for reaction-subdiffusion systems: derivation and stability analysis. AB - We derive general kinetic equations for reacting and subdiffusing entities based on a nonlinear continuous time random walk formalism proposed by Vlad and Ross [Phys. Rev. E 66, 061908 (2002)]. Reaction and diffusion processes are separable in a typical reaction-diffusion system, and their combined influence on the evolution of the density of a species is a simple sum. Our derivation shows that this is no longer true for subdiffusive entities undergoing reactions. The strong memory effects in the transport process, i.e., the non-Markovian nature of subdiffusion, results in a nontrivial combination of reactions and spatial dispersal, which we discuss in detail. We carry out a linear stability analysis of the derived reaction-subdiffusion system to understand the effects of memory on pattern formation. We find that the Turing instability persists in the subdiffusive system. However, the memory modifies the Turing threshold and the characteristics of the band of unstable modes close to this threshold. PMID- 17280133 TI - Breathing dissipative solitons in three-component reaction-diffusion system. AB - We investigate the stability of the localized stationary solutions of a three component reaction-diffusion system with one activator and two inhibitors. A change of the time constants of the inhibitors can lead to a destabilization of the stationary solution. The special case we are interested in is that the breathing mode becomes unstable first and the stationary dissipative soliton undergoes a bifurcation from a stationary to a "breathing" state. This situation is analyzed performing a two-time-scale expansion in the vicinity of the bifurcation point thereby obtaining the corresponding amplitude equation. Also numerical simulations are carried out showing good agreement with the analytical predictions. PMID- 17280134 TI - Ordering dynamics in type-II superconductors. AB - We use analytic and numerical methods to analyze the dynamics of vortices following the quench of a type-II superconductor under the application of an external magnetic field. In three dimensions, in the absence of a field, the spacing between vortices scales with time t with an exponent phi=0.414+/-0.01, in a thin sheet of a superconductor, the scaling exponent is phi=0.294+/-0.01. When an external magnetic field h is applied, the vortices are confined with respect to the length scale of the Abrikosov lattice, leading to a crossover between the power-law scaling length scale and the lattice length scale. From this we suggest a one-parameter scaling of r with h and r that is consistent with numerical data. PMID- 17280135 TI - Evaluation of dynamical models: dissipative synchronization and other techniques. AB - Some recent developments for the validation of nonlinear models built from data are reviewed. Besides giving an overall view of the field, a procedure is proposed and investigated based on the concept of dissipative synchronization between the data and the model, which is very useful in validating models that should reproduce dominant dynamical features, like bifurcations, of the original system. In order to assess the discriminating power of the procedure, four well known benchmarks have been used: namely, Duffing-Ueda, Duffing-Holmes, and van der Pol oscillators, plus the Henon map. The procedure, developed for discrete time systems, is focused on the dynamical properties of the model, rather than on statistical issues. For all the systems investigated, it is shown that the discriminating power of the procedure is similar to that of bifurcation diagrams- which in turn is much greater than, say, that of correlation dimension--but at a much lower computational cost. PMID- 17280136 TI - Distinguishing chaos from noise by scale-dependent Lyapunov exponent. AB - Time series from complex systems with interacting nonlinear and stochastic subsystems and hierarchical regulations are often multiscaled. In devising measures characterizing such complex time series, it is most desirable to incorporate explicitly the concept of scale in the measures. While excellent scale-dependent measures such as epsilon entropy and the finite size Lyapunov exponent (FSLE) have been proposed, simple algorithms have not been developed to reliably compute them from short noisy time series. To promote widespread application of these concepts, we propose an efficient algorithm to compute a variant of the FSLE, the scale-dependent Lyapunov exponent (SDLE). We show that with our algorithm, the SDLE can be accurately computed from short noisy time series and readily classify various types of motions, including truly low dimensional chaos, noisy chaos, noise-induced chaos, random 1/f alpha and alpha stable Levy processes, stochastic oscillations, and complex motions with chaotic behavior on small scales but diffusive behavior on large scales. To our knowledge, no other measures are able to accurately characterize all these different types of motions. Based on the distinctive behaviors of the SDLE for different types of motions, we propose a scheme to distinguish chaos from noise. PMID- 17280137 TI - Adaptation to the edge of chaos in one-dimensional chaotic maps. AB - We present a method that enables chaotic systems to change its dynamics to stable periodic dynamics by a feedback adjustment. The proposed method uses feedback of a largest value obtained from observations of a fixed interval of time series of the system variable and therefore does not require any a priori detailed information. We apply this method to several chaotic systems and confirm numerically that chaotic states are stabilized to stable periodic ones. Since the stabilized states in the system are formed around a boundary between regular states and chaotic ones, the method provides a kind of adaptation to the edge of chaos. PMID- 17280138 TI - Chaotic dynamics and synchronization in microchip solid-state lasers with optoelectronic feedback. AB - We experimentally observe the dynamics of a two-mode Nd:YVO4 microchip solid state laser with optoelectronic feedback. The total laser output is detected and fed back to the injection current of the laser diode for pumping. Chaotic oscillations are observed in the microchip laser with optoelectronic self feedback. We also observe the dynamics of two microchip lasers coupled mutually with optoelectronic link. The output of one laser is detected by a photodiode and the electronic signal converted from the laser output is sent to the pumping of the other laser. Chaotic fluctuation of the laser output is observed when the relaxation oscillation frequency is close to each other between the two microchip lasers. Synchronization of periodic wave form is also obtained when the microchip lasers have a single-longitudinal mode. PMID- 17280139 TI - Synchronization of spontaneous bursting in a CO2 laser. AB - We present experimental and numerical evidence of synchronization of burst events in two different modulated CO2 lasers. Bursts appear randomly in each laser as trains of large amplitude spikes intercalated by a small amplitude chaotic regime. Experimental data and model show the frequency locking of bursts in a suitable interval of coupling strength. We explain the mechanism of this phenomenon and demonstrate the inhibitory properties of the implemented coupling. PMID- 17280140 TI - Spectral form factor near the Ehrenfest time. AB - We calculate the Ehrenfest-time dependence of the leading quantum correction to the spectral form factor of a ballistic chaotic cavity using periodic orbit theory. For the case of broken time-reversal symmetry, when the quantum correction to the form factor involves two small-angle encounters of classical trajectories, our result differs from that previously obtained using field theoretic methods [Tian and Larkin, Phys. Rev. B 70, 035305 (2004)]. While we believe that the existing field-theoretic calculation is technically flawed, the question whether the field theoretic and periodic-orbit approaches agree when more than one small-angle encounter of classical orbits is involved remains unanswered. PMID- 17280141 TI - Spiral wave dynamics under feedback via an equilateral triangular sensory domain. AB - We perform a numerical study of the trajectories of spiral wave cores in excitable systems whose excitability is modulated in proportion to the integral of the activity in a sensory domain in the shape of an equilateral triangle. As a result of this domain shape having vertices opposite sides, unusual forms of lobed limit cycles occur, which are destroyed and then re-form as the domain size is varied. Some key results are also demonstrated experimentally using the light sensitive Belousov-Zhabotinsky reaction. To characterize the observed behavior, we introduce the concept of express and stagnation zones, which are regions where the trajectory moves particularly rapidly or slowly. The location and strength of the zones far from the domain are accounted for by approximating the parts of the spiral wave crossing the domain by a series of plane waves. PMID- 17280142 TI - Lyapunov exponents for small aspect ratio Rayleigh-Benard convection. AB - Leading order Lyapunov exponents and their corresponding eigenvectors have been computed numerically for small aspect ratio, three-dimensional Rayleigh-Benard convection cells with no-slip boundary conditions. The parameters are the same as those used by Ahlers and Behringer [Phys. Rev. Lett. 40, 712 (1978)] and Gollub and Benson [J. Fluid Mech. 100, 449 (1980)] in their work on a periodic time dependence in Rayleigh-Benard convection cells. Our work confirms that the dynamics in these cells truly are chaotic as defined by a positive Lyapunov exponent. The time evolution of the leading order Lyapunov eigenvector in the chaotic regime will also be discussed. In addition we study the contributions to the leading order Lyapunov exponent for both time periodic and aperiodic states and find that while repeated dynamical events such as dislocation creation/annihilation and roll compression do contribute to the short time Lyapunov exponent dynamics, they do not contribute to the long time Lyapunov exponent. We find instead that nonrepeated events provide the most significant contribution to the long time leading order Lyapunov exponent. PMID- 17280143 TI - Cascade of circulations in fluid turbulence. AB - Kelvin's theorem on conservation of circulations is an essential ingredient of Taylor's theory of turbulent energy dissipation by the process of vortex-line stretching. In previous work, we have proposed a nonlinear mechanism for the breakdown of Kelvin's theorem in ideal turbulence at infinite Reynolds number. We develop here a detailed physical theory of this cascade of circulations. Our analysis is based upon an effective equation for large-scale coarse-grained velocity, which contains a turbulent-induced vortex force that can violate Kelvin's theorem. We show that singularities of sufficient strength, which are observed to exist in turbulent flow, can lead to nonvanishing dissipation of circulation for an arbitrarily small coarse-graining length in the effective equations. This result is an analog for circulation of Onsager's theorem on energy dissipation for singular Euler solutions. The physical mechanism of the breakdown of Kelvin's theorem is diffusion of lines of large-scale vorticity out of the advected loop. This phenomenon can be viewed as a classical analog of the Josephson-Anderson phase-slip phenomenon in superfluids due to quantized vortex lines. We show that the circulation cascade is local in scale and use this locality to develop concrete expressions for the turbulent vortex force by a multiscale gradient expansion. We discuss implications for Taylor's theory of turbulent dissipation and we point out some related cascade phenomena, in particular for magnetic flux in magnetohydrodynamic turbulence. PMID- 17280144 TI - Analytical and numerical study on a vortex sheet in incompressible Richtmyer Meshkov instability in cylindrical geometry. AB - Motion of a fluid interface in the Richtmyer-Meshkov instability in cylindrical geometry is examined analytically and numerically. Nonlinear stability analysis is performed in order to clarify the dependence of growth rates of a bubble and spike on the Atwood number and mode number n involved in the initial perturbations. We discuss differences of weakly and fully nonlinear evolution in cylindrical geometry from that in planar geometry. It is shown that the analytical growth rates coincide well with the numerical ones up to the neighborhood of the break down of numerical computations. Long-time behavior of the fluid interface as a vortex sheet is numerically investigated by using the vortex method and the roll up of the vortex sheet is discussed for different Atwood numbers. The temporal evolution of the curvature of a bubble and spike for several mode numbers is investigated and presented that the curvature of spikes is always larger than that of bubbles. The circulation and the strength of the vortex sheet at the fully nonlinear stage are discussed, and it is shown that their behavior is different for the cases that the inner fluid is heavier than the outer one and vice versa. PMID- 17280145 TI - Spatial correlation of temperature in turbulent Rayleigh-Benard convection. AB - A cubic Rayleigh-Benard cell is operated at a Rayleigh number of 1.5x10(9) and a Prandtl number of 6.1. The cell is equipped with thermistors placed along the vertical line through the center of the cell. The spatial correlation of temperature is deduced from simultaneous temperature recordings from these thermistors. The correlation function is well fitted by the sum of two exponentials. There is no cascade in the temperature field as only two characteristic length scales appear. The direct measurement of spatial correlations allows us to test the validity of Taylor's hypothesis in this flow. PMID- 17280146 TI - Physical distinction between rolling-grain ripples and vortex ripples: an experimental study. AB - We have performed an experimental study of the transition of rolling-grain ripples toward vortex ripples. In particular, we have looked for the influence of the grains' diameter, the frequency of oscillation, and the grains' cohesion. We demonstrate that the rolling-grain ripples are transient patterns which do appear as soon as we are close to the threshold for grain motion, whereas vortex ripples are always the final patterns observed and are the only patterns observed if one is far from the threshold for grain motion. Our results show that the "elasticity" (i.e., the tendency to modify the wavelength by either compression or dilatation) of the vortex ripples explains several discrepancies with respect to the observed evolutions and measurements reported so far in the literature. PMID- 17280147 TI - Dynamics of liquid rope coiling. AB - We present a combined experimental and numerical investigation of the coiling of a liquid "rope" falling on a solid surface, focusing on three little-explored aspects of the phenomenon: The time dependence of "inertio-gravitational" coiling, the systematic dependence of the radii of the coil and the rope on the experimental parameters, and the "secondary buckling" of the columnar structure generated by high-frequency coiling. Inertio-gravitational coiling is characterized by oscillations between states with different frequencies, and we present experimental observations of four distinct branches of such states in the frequency-fall height space. The transitions between coexisting states have no characteristic period, may take place with or without a change in the sense of rotation, and usually (but not always) occur via an intermediate "figure of eight" state. We present extensive laboratory measurements of the radii of the coil and of the rope within it, and show that they agree well with the predictions of a "slender-rope" numerical model. Finally, we use dimensional analysis to reveal a systematic variation of the critical column height for secondary buckling as a function of (dimensionless) flow rate and surface tension parameters. PMID- 17280148 TI - Optic cavitation in an ultrasonic field. AB - Cavitation bubbles are generated in water by low-energy femtosecond laser pulses in the presence of an ultrasonic field. Bubble dynamics and cavitation luminescence are investigated by CCD photography and photomultiplier measurements in dependence on the phase of the acoustic cycle at which the bubbles are generated. The experimental results demonstrate that the initially small laser generated bubbles can be expanded significantly by the sound field and that weak cavitation luminescence can be observed in two small intervals of the seeding phase. The luminescence yield sensitively depends on the degree of sphericity of bubble collapse. PMID- 17280149 TI - Limits of the potential flow approach to the single-mode Rayleigh-Taylor problem. AB - We report on the behavior of a single-wavelength Rayleigh-Taylor flow at late times. The calculations were performed in a long square duct (lambda x lambda x 8lambda), using four different numerical simulations. In contradiction with potential flow theories that predict a constant terminal velocity, the single wavelength Rayleigh-Taylor problem exhibits late-time acceleration. The onset of acceleration occurs as the bubble penetration depth exceeds the diameter of bubbles, and is observed for low and moderate density differences. Based on our simulations, we provide a phenomenological description of the observed acceleration, and ascribe this behavior to the formation of Kelvin-Helmholtz vortices on the bubble-spike interface that diminish the friction drag, while the associated induced flow propels the bubbles forward. For large density ratios, the formation of secondary instabilities is suppressed, and the bubbles remain terminal consistent with potential flow models. PMID- 17280150 TI - Sub- and superdiffusive molecular displacement laws in disordered porous media probed by nuclear magnetic resonance. AB - Hydrodynamic dispersion of water flowing through porous glasses with nominal pore sizes in the range 40 to 160 micrometers was studied with the aid of a pulsed gradient nuclear magnetic resonance technique compensating for coherent flow velocities. The crossover from effectively subdiffusive mean square displacement, proportional variant t0.84, in the absence of hydrodynamic flow to a superdiffusive, almost ballistic power law, proportional, variant t1.95, at the highest flow rates was observed. At intermediate flow rates, a gradual conversion between these two limiting power laws occurs. As a function of the Peclet number, the effective dispersion coefficient is in accordance with a power law with an exponent 1.2. PMID- 17280151 TI - Large- and small-scale interactions and quenching in an alpha2-dynamo. AB - The evolution of the large-scale magnetic field in a turbulent flow of conducting fluid is considered in the framework of a multiscale alpha2-dynamo model, which includes the poloidal and the toroidal components for the large-scale magnetic field and a shell model for the small-scale magnetohydrodynamical turbulence. The conjugation of the mean-field description for the large-scale field and the shell formalism for the small-scale turbulence is based on strict conformity to the conservation laws. The model displays a substantial magnetic contribution to the alpha effect. It was shown that a large-scale magnetic field can be generated by current helicity even solely. The alpha quenching and the role of the magnetic Prandtl number (Pm) are studied. We have determined the dynamic nature of the saturation mechanism of dynamo action. Any simultaneous cross correlation of alpha and large-scale magnetic field energy EB is negligible, whereas coupling between alpha and EB becomes substantial for moderate time lags. An unexpected result is the behavior of the large-scale magnetic energy with variation of the magnetic Prandtl number. Diminishing of Pm does not have an inevitable ill effect on the magnetic field generation. The most efficient large-scale dynamo operates under relatively low Prandtl numbers--then the small-scale dynamo is suppressed and the decrease of Pm can lead even to superequipartition of the large-scale magnetic field (i.e., EB>Eu). In contrast, the growth of Pm does not promote the large-scale magnetic field generation. A growing counteraction of the magnetic alpha effect reduces the level of mean large-scale magnetic energy at the saturated state. PMID- 17280152 TI - Liquid flow in surface-nanostructured channels studied by molecular dynamics simulation. AB - Molecular dynamics simulations have been carried out to investigate the fluid wetting and flow in nanochannels whose surfaces are structured by an array of nanoscale triangular modules. We find that the surface nanostructures have a dual effect on the boundary slip and friction of the liquid nanoflow. On the one hand, the nanostructures can enhance the surface hydrophilicity for a hydrophilic liquid-solid interaction, and can increase the hydrophobicity for a hydrophobic interaction due to a nanoscale lotus effect. In particular, the nanostructured surface may show superhydrophobicity and lead to the large velocity slip of the liquid flow. On the other hand, simultaneously, the nanostructures distort the nanoscale streamlines of the liquid flow near the channel surfaces and block the nanoflow directly, which decreases the apparent slip length equivalently. The dual effect of the nanostructures on the surface wettability and the hydrodynamic disturbance results in a nonmonotonic dependence of the slip length on the nanostructure size. The simulations imply that the surface nanostructures can be applied to control the friction of liquid micro- and nanoflows. PMID- 17280153 TI - Role of excited atoms in decaying low-pressure argon plasma. AB - The influence of the kinetics of excited atoms on the characteristics of an inductively coupled plasma in argon during the early afterglow is studied. A self consistent model including the nonlocal approach for the kinetic treatment of the electrons is applied. Parameters of both the steady state of the rf discharge and the decay phase are presented. Results for the steady-state densities of excited atoms as well as temporal evolutions of the wall potential and mean energy of electrons are discussed in comparison with experimental data available from the literature. The ionization kinetics of the electrons, the electron power balance, and the main kinetic pathways for excited argon atoms are analyzed in the pressure range between 0.5 and 133 Pa . In particular, a significant influence of the excited atoms on the plasma behavior in steady state and during the afterglow is found. PMID- 17280154 TI - Characteristics of multiple filaments generated by femtosecond laser pulses in air: prefocused versus free propagation. AB - The characteristics of the multiple filaments formed by prefocused and freely propagating femtosecond laser pulses are investigated and compared. It is shown in our experiments that the diameter, length, stability, and interaction for the two cases can be quite different. The filaments formed by prefocused beam indicate dynamic spatial evolution with higher laser intensity and electron density. They have a typical diameter of 100 microm are of shorter length. In the free propagation case, the filaments exhibit interesting properties such as hundred-meter propagation distance and mm-size diameter. Moreover, only the interaction of the filaments with the energy background affects the evolution of the filaments. Filament-filament interactions such as the filament splitting and merging were not observed in this case. PMID- 17280155 TI - Rotational motion of dusty structures in glow discharge in longitudinal magnetic field. AB - The investigation of dust structure formed in glow discharge in an external longitudinal magnetic field with induction up to 400 G applied is presented in this work. The dust structure starts to rotate in the magnetic field. The angular velocity magnitude is one to two orders larger than one in other discharge types. Its dependence on the magnetic field is nonmonotonic. The rotation direction inverses with an increase of the magnetic induction value up to a certain magnitude B0. In close range of induction around B0 and under certain conditions the rotation of the upper and lower parts of the structure in the opposite direction is observed. Rotation is caused by the ion-drag force. The inversion of rotation direction relates with the change of plasma flows in the area of their formation in stratum with the magnetic field applied. The effect of ion flows was investigated in two additional experiments on the observation of structure rotation onset and on gravity-driven probing of stratum. The angular-velocity unhomogeniety allowed us to investigate shearing and to observe melting of the dust crystal. The correlation functions approach showed the occurrence of structure transformation and its phase transition of the meltinglike type in the magnetic field. PMID- 17280156 TI - Stability diagram of unilateral buckling patterns of strip-delaminated films. AB - Thin films deposited on substrates are usually submitted to large residual compression stresses, causing delamination and buckling of the film into various patterns. The present study is focused on the different equilibria arising on strip-shaped delaminated areas. The three most common types of buckling patterns observed on such strips are known as the straight-sided wrinkles, bubble pattern, and telephone cord blisters. The stability of those equilibria as a function of the two stress components of the loading is investigated. The Foppl-Von Karman model for elastic plates is used for theoretical aspects. The post-critical equilibrium paths of the buckling patterns are investigated numerically by means of the finite-element method. The substrate is assumed to be rigid and the contact to be frictionless. The equilibrium solutions can be classified into families of homologous equilibria allowing the identification of dimensionless parameters for the study of stability. A mapping of the different stable post critical equilibria is given. It is shown that the straight-sided wrinkles and the bubbles are associated with anisotropy of stresses and/or of elastic properties, whereas the telephone cords are stable at high isotropic stresses. The morphological transitions are experimentally evidenced by in situ atomic force microscopy observations of a nickel 50-nm-thick film under stress. PMID- 17280157 TI - Optimization of soliton ratchets in inhomogeneous sine-Gordon systems. AB - Unidirectional motion of solitons can take place, although the applied force has zero average in time, when the spatial symmetry is broken by introducing a potential V(x) , which consists of periodically repeated cells with each cell containing an asymmetric array of strongly localized inhomogeneities at positions xi. A collective coordinate approach shows that the positions, heights, and widths of the inhomogeneities (in that order) are the crucial parameters so as to obtain an optimal effective potential Uopt that yields a maximal average soliton velocity. Uopt essentially exhibits two features: double peaks consisting of a positive and a negative peak, and long flat regions between the double peaks. Such a potential can be obtained by choosing inhomogeneities with opposite signs (e.g., microresistors and microshorts in the case of long Josephson junctions) that are positioned close to each other, while the distance between each peak pair is rather large. These results of the collective variable theory are confirmed by full simulations for the inhomogeneous sine-Gordon system. PMID- 17280158 TI - Near-field characterization of effective optical interfaces. AB - The properties of many heterogeneous media depend on both the surface roughness and the local variations of the optical properties. An effective optical interface is usually invoked to describe the characteristics of such media. Using approaches specific to near-field optics, the two influences can be decoupled and a quantitative assessment of their contributions can be performed. It is also shown that a discrete random-walk model can be used to determine the magnitude of the dielectric constant fluctuations at subwavelength scales which, in turn, describe the morphology of optically inhomogeneous media. PMID- 17280159 TI - Localized states in a triangular set of linearly coupled complex Ginzburg-Landau equations. AB - We introduce a pattern-formation model based on a symmetric system of three linearly coupled cubic-quintic complex Ginzburg-Landau equations, which form a triangular configuration. This is the simplest model of a multicore fiber laser. We identify stability regions for various types of localized patterns possible in this setting, which include stationary and breathing triangular vortices. PMID- 17280160 TI - Superconducting pipes and levitating magnets. AB - Motivated by a beautiful demonstration of the Faraday and the Lenz laws in which a small neodymium magnet falls slowly through a conducting nonferromagnetic tube, we consider the dynamics of a magnet falling coaxially through a superconducting pipe. Unlike the case of normal conducting pipes, in which the magnet quickly reaches the terminal velocity, inside a superconducting tube the magnet falls freely. On the other hand, to enter the pipe the magnet must overcome a large electromagnetic energy barrier. For sufficiently strong magnets, the barrier is so large that the magnet will not be able to penetrate it and will be levitated over the mouth of the pipe. We calculate the work that must done to force the magnet to enter a superconducting tube. The calculations show that superconducting pipes are very efficient at screening magnetic fields. For example, the magnetic field of a dipole at the center of a short pipe of radius a and length L approximately > a decays, in the axial direction, with a characteristic length xi approximately 0.26a. The efficient screening of the magnetic field might be useful for shielding highly sensitive superconducting quantum interference devices. Finally, the motion of the magnet through a superconducting pipe is compared and contrasted to the flow of ions through a trans-membrane channel. PMID- 17280161 TI - High-order-mode soliton structures in two-dimensional lattices with defocusing nonlinearity. AB - While fundamental-mode discrete solitons have been demonstrated with both self focusing and defocusing nonlinearity, high-order-mode localized states in waveguide lattices have been studied thus far only for the self-focusing case. In this paper, the existence and stability regimes of dipole, quadrupole, and vortex soliton structures in two-dimensional lattices induced with a defocusing nonlinearity are examined by the theoretical and numerical analysis of a generic envelope nonlinear lattice model. In particular, we find that the stability of such high-order-mode solitons is quite different from that with self-focusing nonlinearity. As a simple example, a dipole ("twisted") mode soliton with adjacent excited sites which may be stable in the focusing case becomes unstable in the defocusing regime. Our results may be relevant to other two-dimensional defocusing periodic nonlinear systems such as Bose-Einstein condensates with a positive scattering length trapped in optical lattices. PMID- 17280162 TI - Bragg transmittance of s-polarized waves through finite-thickness photonic crystals with a periodically corrugated interface. AB - Finite-thickness photonic crystals (PC's) with periodically corrugated interfaces are suggested to realize some unusual features in the behavior of transmitted Bragg beams (diffraction orders). The scattering of s -polarized plane waves by such structures is studied. It follows from the numerical results that rather thin corrugated PC's borrow their basic properties from both conventional PC's and gratings, leading to some new effects. In particular, a shift of the actual cutoff frequencies towards larger values than those of the Rayleigh cutoff frequencies can be obtained due to the ordinary opaque range in transmission, within which all propagative orders vanish. This effect can even be enhanced due to the nonordinary behavior arising at the edges of the ordinary opaque range, which manifests itself in that some but not all propagative orders in transmission are suppressed. Hence the opaque ranges for individual orders are wider than the corresponding ordinary range. Besides, frequency ranges exist which are not connected with the edge of the ordinary opaque range, where a similar nonordinary effect does appear. As a result, each propagative order in transmission generally has its own set of opaque ranges. Only a single order can be contributive while several others are formally propagative, too. The corrugations have to be located at the upper interface in order to realize these nonordinary effects. Moving the corrugation from the upper to the lower interface leads to a disappearance of the observed effects, so that their nature cannot be explained exclusively in terms of matching the wave vectors of the diffraction orders and the Floquet-Bloch waves. The conventional sequence of cutoffs for different diffraction orders with respect to each other can be changed for certain structures if the rods of a PC are made of Drude metal. Hence, transmission regimes can be realized which are beyond the classical theory of gratings. Several effects arising when varying the angle of incidence are demonstrated and briefly discussed. The detected effects can be used for controlling the number of actually contributive beams and for obtaining alternating ranges of single-beam and multibeam operation, which should lead to extending the potentials of optical and microwave technologies based on the use of single-beam and multibeam regimes. PMID- 17280163 TI - Hole-vortex solitons. AB - Three-dimensional two-component solitons, propagating in long-short wave resonance mode, are predicted. If the spectrum of the short-wave component lies in the area of normal group velocity dispersion, these solitons have transverse structure in the form of hole-vortex field defects on an infinite background. In the opposite case two-component "bullets" or the "bright" vortex and the "bullet" with a hole in the center can exist. The stability region of the considered objects is estimated on the basis of a variational approach. As a concrete physical model we consider the propagation of electromagnetic pulses in a uniaxial crystal. Here the ordinary component of the pulse is the short wave, and its extraordinary component is the long wave. PMID- 17280164 TI - Broadband diffraction management and self-collimation of white light in photonic lattices. AB - We introduce periodic photonic structures where the strength of diffraction can be managed in a very broad frequency range. We show how to design arrays of curved waveguides where light beams experience wavelength-independent normal, anomalous, or zero diffraction. Our results suggest opportunities for efficient self-collimation, focusing, and reshaping of beams produced by white-light and supercontinuum sources. We also predict a possibility of multicolor Talbot effect, which is not possible in free space or conventional photonic lattices. PMID- 17280165 TI - Geometrical aspects in optical wave-packet dynamics. AB - We construct a semiclassical theory for propagation of an optical wave packet in a nonconducting medium with a periodic structure of dielectric permittivity and magnetic permeability, i.e., a nonconducting photonic crystal. We employ a quantum-mechanical formalism in order to clarify its link to those of electronic systems. It involves the geometrical phase, i.e., Berry's phase, in a natural way, and describes an interplay between orbital motion and internal rotation. Based on the above theory, we discuss the geometrical aspects of the optical Hall effect. We also consider a reduction of the theory to a system without periodic structure and apply it to the transverse shift of an optical beam at an interface reflection or refraction. For a generic incident beam with an arbitrary polarization, an identical result for the transverse shift of each reflected or transmitted beam is given by the following different approaches: (i) analytic evaluation of wave-packet dynamics, (ii) total angular momentum (TAM) conservation for individual photons, and (iii) numerical simulation of wave packet dynamics. It is consistent with a result by classical electrodynamics. This means that the TAM conservation for individual photons is already taken into account in wave optics, i.e., classical electrodynamics. Finally, we show an application of our theory to a two-dimensional photonic crystal, and propose an optimal design for the enhancement of the optical Hall effect in photonic crystals. PMID- 17280166 TI - Bragg-soliton formation and pulse compression in a one-dimensional periodic structure. AB - We present a method for efficiently exciting a Bragg soliton with a spectral content located mostly within the bandgap of a one-dimensional periodic structure. The method is based on a new interaction between Bragg solitons and on a high intensity enhancement, caused owing to the reduced propagation velocity inside periodic structures. Our method can also be used for efficient compression of optical pulses. We have theoretically demonstrated pulse compression with a compression ratio of 2800--over two orders of magnitude higher than previously reported. The results open new possibilities for experimental demonstration of Bragg soliton propagation and for pulse compression in one-dimensional periodic structures. PMID- 17280167 TI - Helmholtz-Manakov solitons. AB - A different spatial soliton-bearing wave equation is introduced, the Helmholtz Manakov (HM) equation, for describing the evolution of broad multicomponent self trapped beams in Kerr-type media. By omitting the slowly varying envelope approximation, the HM equation can describe accurately vector solitons propagating and interacting at arbitrarily large angles with respect to the reference direction. The HM equation is solved using Hirota's method, yielding four different classes of Helmholtz soliton that are vector generalizations of their scalar counterparts. General and particular forms of the three invariants of the HM system are also reported. PMID- 17280168 TI - Frozen light in photonic crystals with degenerate band edge. AB - Consider a plane monochromatic wave incident on a semi-infinite periodic structure. What happens if the normal component of the transmitted wave group velocity vanishes? At first sight, zero normal component of the transmitted wave group velocity simply implies total reflection of the incident wave. But we demonstrate that total reflection is not the only possible outcome. Instead, the transmitted wave can appear in the form of a frozen mode with very large diverging amplitude and either zero, or purely tangential energy flux. The field amplitude in the transmitted wave can exceed that of the incident wave by several orders of magnitude. There are two qualitatively different kinds of frozen mode regime. The first one is associated with a stationary inflection point of electromagnetic dispersion relation. This phenomenon has been analyzed in our previous papers. Now, our focus is on the frozen mode regime related to a degenerate photonic band edge. An advantage of this phenomenon is that it can occur in much simpler periodic structures. This spectacular effect is extremely sensitive to the frequency and direction of propagation of the incident plane wave. These features can be very attractive in a variety of practical applications, such as higher harmonic generation and wave mixing, light amplification and lasing, highly efficient superprizms, etc. PMID- 17280169 TI - Stable solitons of even and odd parities supported by competing nonlocal nonlinearities. AB - We introduce a one-dimensional phenomenological model of a nonlocal medium featuring focusing cubic and defocusing quintic nonlocal optical nonlinearities. By means of numerical methods, we find families of solitons of two types, even parity (fundamental) and dipole-mode (odd-parity) ones. Stability of the solitons is explored by means of computation of eigenvalues associated with modes of small perturbations, and tested in direct simulations. We find that the stability of the fundamental solitons strictly follows the Vakhitov-Kolokolov criterion, whereas the dipole solitons can be destabilized through a Hamiltonian-Hopf bifurcation. The solitons of both types may be stable in the nonlocal model with only quintic self-attractive nonlinearity, in contrast with the instability of all solitons in the local version of the quintic model. PMID- 17280171 TI - Inhomogeneous backflow transformations in quantum Monte Carlo calculations. AB - An inhomogeneous backflow transformation for many-particle wave functions is presented and applied to electrons in atoms, molecules, and solids. We report variational and diffusion quantum Monte Carlo (VMC and DMC) energies for various systems and study the computational cost of using backflow wave functions. We find that inhomogeneous backflow transformations can provide a substantial increase in the amount of correlation energy retrieved within VMC and DMC calculations. The backflow transformations significantly improve the wave functions and their nodal surfaces. PMID- 17280170 TI - Matter-wave solitons in radially periodic potentials. AB - We investigate two-dimensional (2D) states in Bose-Einstein condensates with self attraction or self-repulsion, trapped in an axially symmetric optical-lattice potential periodic along the radius. The states trapped both in the central potential well and in remote circular troughs are studied. In the repulsive mode, a new soliton species is found, in the form of radial gap solitons. The latter solitons are completely stable if they carry zero vorticity (l=0) , while with l not equal 0 they develop a weak azimuthal modulation, which makes them rotating patterns, that persist indefinitely long. In addition, annular gap solitons may support stable azimuthal dark-soliton pairs on their crests. In remote troughs of the attractive model, stable localized states may assume a ringlike shape with weak azimuthal modulation, or shrink into solitons strongly localized in the azimuthal direction, which is explained in the framework of an averaged 1D equation with the cyclic azimuthal coordinate. Numerical simulations of the attractive model also reveal stable necklacelike patterns, built of several strongly localized peaks. Dynamics of strongly localized solitons circulating in the troughs is studied too. While the solitons with sufficiently small velocities are completely stable, fast solitons gradually decay, due to the leakage of matter into the adjacent trough, under the action of the centrifugal force. Investigation of head-on collisions between strongly localized solitons traveling in circular troughs shows that collisions between in-phase solitons in a common trough lead to collapse, while pi-out-of-phase solitons bounce many times, but eventually merge into a single one, without collapsing. In-phase solitons colliding in adjacent circular troughs also tend to merge into a single soliton. PMID- 17280172 TI - Computational method for the quantum Hamilton-Jacobi equation: one-dimensional scattering problems. AB - One-dimensional scattering problems are investigated in the framework of the quantum Hamilton-Jacobi formalism. First, the pole structure of the quantum momentum function for scattering wave functions is analyzed. The significant differences of the pole structure of this function between scattering wave functions and bound state wave functions are pointed out. An accurate computational method for the quantum Hamilton-Jacobi equation for general one dimensional scattering problems is presented to obtain the scattering wave function and the reflection and transmission coefficients. The computational approach is demonstrated by analysis of scattering from a one-dimensional potential barrier. We not only present an alternative approach to the numerical solution of the wave function and the reflection and transmission coefficients but also provide a computational aspect within the quantum Hamilton-Jacobi formalism. The method proposed here should be useful for general one-dimensional scattering problems. PMID- 17280173 TI - Bayesian update method for adaptive weighted sampling. AB - Exploring conformational spaces is still a challenging task for simulations of complex systems. One way to enhance such a task is weighted sampling, e.g., by assigning high weights to regions that are rarely sampled. It is, however, difficult to estimate adequate weights beforehand, and therefore adaptive methods are desired. Here we present a method for adaptive weighted sampling based on Bayesian inference. Within the framework of Bayesian inference, we develop an update scheme in which the information from previous data is stored in a prior distribution which is then updated to a posterior distribution according to new data. The method proposed here is particularly well suited for distributed computing, in which one must deal with rapid influxes of large amounts of data. PMID- 17280174 TI - Parallel self-consistent-field calculations via Chebyshev-filtered subspace acceleration. AB - Solving the Kohn-Sham eigenvalue problem constitutes the most computationally expensive part in self-consistent density functional theory (DFT) calculations. In a previous paper, we have proposed a nonlinear Chebyshev-filtered subspace iteration method, which avoids computing explicit eigenvectors except at the first self-consistent-field (SCF) iteration. The method may be viewed as an approach to solve the original nonlinear Kohn-Sham equation by a nonlinear subspace iteration technique, without emphasizing the intermediate linearized Kohn-Sham eigenvalue problems. It reaches self-consistency within a similar number of SCF iterations as eigensolver-based approaches. However, replacing the standard diagonalization at each SCF iteration by a Chebyshev subspace filtering step results in a significant speedup over methods based on standard diagonalization. Here, we discuss an approach for implementing this method in multi-processor, parallel environment. Numerical results are presented to show that the method enables to perform a class of highly challenging DFT calculations that were not feasible before. PMID- 17280175 TI - Vibrations of adsorbates on metal surfaces from geometry optimizations. AB - We present a method to compute harmonic vibrations that uses the structures and the forces in the structures that are obtained from a geometry optimization. It does not require any additional electronic structure calculations. The method generally takes only on the order of minutes on a regular PC, but it does not guarantee the calculation of all vibrations of a system. Tests on small adsorbates on a transition metal surface show, however, that the most relevant vibrations are obtained. An important part of the method is the inclusion of several checks to determine the reliability of its results, which gives also error estimates of the vibrational frequencies. PMID- 17280176 TI - Stability of discrete solitons in the presence of parametric driving. AB - In this Brief Report, we consider parametrically driven bright solitons in the vicinity of the anticontinuum limit. We illustrate the mechanism through which these solitons become unstable due to the collision of the phase mode with the continuous spectrum, or eigenvalues bifurcating thereof. We show how this mechanism typically leads to complete destruction of the bright solitary wave. PMID- 17280177 TI - Analytical calculation of the self-force on a part of a current loop using standard electrodynamics. AB - The self-force experienced by a semicircular conducting loop of circular cross section is evaluated analytically using the Lorentz force expression and shown to agree with the result of the partially analytical and partially numerical calculations quoted in the paper of Cavalleri [Phys. Rev. E 58, 2505 (1998)]. PMID- 17280178 TI - Modulational instability of spatially broadband nonlinear optical pulses in four state atomic systems. AB - The modulational instability of broadband optical pulses in a four-state atomic system is investigated. In particular, starting from a recently derived generalized nonlinear Schrodinger equation, a wave-kinetic equation is derived. A comparison between coherent and random-phase wave states is made. It is found that the spatial spectral broadening can contribute to the nonlinear stability of ultrashort optical pulses. In practical terms, this could be achieved by using random-phase plate techniques. PMID- 17280179 TI - Comment on "Electron acceleration by an intense short pulse laser in a static magnetic field in vacuum". AB - K. P. Singh [Phys. Rev. E 69, 056410 (2004)] put forward a scheme of vacuum laser acceleration in a static magnetic field. We point out that one of the assumptions used in their model does not stand on a solid physical ground and that it seriously influences electrons to obtain net energy gains from the laser field. PMID- 17280180 TI - Comment on "Numerical methods for stochastic differential equations". AB - Wilkie [Phys. Rev. E 70, 017701 (2004)] used a heuristic approach to derive Runge Kutta-based numerical methods for stochastic differential equations based on methods used for solving ordinary differential equations. The aim was to follow solution paths with high order. We point out that this approach is invalid in the general case and does not lead to high order methods. We warn readers against the inappropriate use of deterministic calculus in a stochastic setting. PMID- 17280181 TI - Quantum contextuality in a single-neutron optical experiment. AB - An experimental demonstration of quantum contextuality with neutrons is presented, which intended to exhibit a Kochen-Specker-like phenomenon. Since no perfect correlation is expected in practical experiments, inequalities are derived to distinguish quantitatively the obtained results from predictions by a noncontextual hidden variable theory. Experiments were accomplished with the use of a neutron interferometer combined with spinor manipulation devices. The results clearly violate the prediction of noncontextual theories. PMID- 17280182 TI - Signatures of strong momentum localization via entanglement of translational and internal states. AB - We show that atoms or molecules subject to fields that couple their internal and translational (momentum) states may undergo a crossover from randomization (diffusion) to strong localization (sharpening) of their momentum distribution. The predicted crossover should be manifest by a drastic change of the interference pattern as a function of the coupling fields. PMID- 17280183 TI - Demixing of bosonic mixtures in optical lattices from macroscopic to microscopic scales. AB - Mixtures of cold bosonic atoms in optical lattices undergo demixing on different length scales with increasing interspecies repulsion. As a general rule, the stronger the intraspecies interactions, the shorter is this length scale. The wealth of phenomena is documented by illustrative examples on both superfluids and Mott insulators. PMID- 17280184 TI - BCS-BEC crossover on the two-dimensional honeycomb lattice. AB - The attractive Hubbard model on the honeycomb lattice exhibits, at half filling, a quantum critical point between a semimetal with massless Dirac fermions and an s-wave superconductor (SC). We study the BCS-BEC crossover in this model away from half filling at zero temperature and show that the appropriately defined crossover line (in the interaction-density plane) passes through the quantum critical point at half filling. For a range of densities around half filling, the "underlying Fermi surface" of the SC, defined as the momentum space locus of minimum energy quasiparticle excitations, encloses an area which changes nonmonotonically with interaction. We also study fluctuations in the SC and the semimetal, and show the emergence of an undamped Leggett mode deep in the SC. Finally, we consider possible implications for ultracold atoms in optical lattices and the high temperature SCs. PMID- 17280186 TI - Measurement of the translational and rotational Brownian motion of individual particles in a rarefied gas. AB - We measured the free Brownian motion of individual spherical and the Brownian rotation of individual nonspherical micrometer-sized particles in rarefied gas. Measurements were done with high spatial and temporal resolution under microgravity conditions in the Bremen drop tower so that the transition from diffusive to ballistic motion could be resolved. We find that the translational and rotational diffusion can be described by the relation given by Uhlenbeck and Ornstein [Phys. Rev. 36, 823 (1930)]. Measurements of rotational Brownian motion can be used for the determination of the moments of inertia of small particles. PMID- 17280185 TI - Producing cluster states in charge qubits and flux qubits. AB - We propose a method to efficiently generate cluster states in charge qubits, both semiconducting and superconducting, as well as flux qubits. We show that highly entangled cluster states can be realized by a "one-touch" entanglement operation by tuning gate bias voltages for charge qubits. We also investigate the robustness of these cluster states for nonuniform qubits, which are unavoidable in solid-state systems. We find that quantum computation based on cluster states is a promising approach for solid-state qubits. PMID- 17280187 TI - First-passage Monte Carlo algorithm: diffusion without all the hops. AB - We present a novel Monte Carlo algorithm for N diffusing finite particles that react on collisions. Using the theory of first-passage processes and time dependent Green's functions, we break the difficult N-body problem into independent single- and two-body propagations circumventing numerous diffusion hops used in standard Monte Carlo simulations. The new algorithm is exact, extremely efficient, and applicable to many important physical situations in arbitrary integer dimensions. PMID- 17280189 TI - Short-path statistics and the diffusion approximation. AB - In the field of first return time statistics in bounded domains, short paths may be defined as those paths for which the diffusion approximation is inappropriate. This is at the origin of numerous open questions concerning the characterization of residence time distributions. We show here how general integral constraints can be derived that make it possible to address short-path statistics indirectly by application of the diffusion approximation to long paths. Application to the moments of the distribution at the low-Knudsen limit leads to simple practical results and novel physical pictures. PMID- 17280188 TI - Critical behavior of colloid-polymer mixtures in random porous media. AB - We show that the critical behavior of a colloid-polymer mixture inside a random porous matrix of quenched hard spheres belongs to the universality class of the random-field Ising model. We also demonstrate that random-field effects in colloid-polymer mixtures are surprisingly strong. This makes these systems attractive candidates to study random-field behavior experimentally. PMID- 17280190 TI - High frequency atomic magnetometer by use of electromagnetically induced transparency. AB - Atomic magnetometers have achieved magnetic sensitivities in the subfemtotesla regime. Their bandwidth is determined by the transverse spin relaxation rate, 1/T2, which also determines the magnetic sensitivity. It is theoretically demonstrated that by using an electromagnetically induced transparent probe beam in a pump-probe atomic magnetometer, it is possible to operate the latter at frequencies much higher than its bandwidth, maintaining a high signal-to-noise ratio. PMID- 17280191 TI - Second dip as a signature of ultrahigh energy proton interactions with cosmic microwave background radiation. AB - We discuss as a new signature for the interaction of extragalactic ultrahigh energy protons with cosmic microwave background radiation a spectral feature located at E= 6.3 x 10(19) eV in the form of a narrow and shallow dip. It is produced by the interference of e+e(-)-pair and pion production. We show that this dip and, in particular, its position are almost model-independent. Its observation by future ultrahigh energy cosmic ray detectors may give the conclusive confirmation that an observed steepening of the spectrum is caused by the Greisen-Zatsepin-Kuzmin effect. PMID- 17280192 TI - Can cosmic structure form without dark matter? AB - One of the prime pieces of evidence for dark matter is the observation of large overdense regions in the Universe. To account for this observation, perturbations had to have grown since recombination by a factor greater than (1+z*) approximately 1180 where z* is the epoch of recombination. This enhanced growth does not happen in general relativity, and so dark matter is needed in the standard theory. We show here that enhanced growth can occur in alternatives to general relativity, in particular, in Bekenstein's relativistic version of modified Newtonian dynamics. PMID- 17280193 TI - Open M5-branes. AB - We show how, in heterotic M theory, an M5-brane in the 11-dimensional bulk may end on an "M9-brane" boundary, the M5-brane boundary being a Yang-monopole 4 brane. This possibility suggests various novel 5-brane configurations of heterotic M theory, in particular, a static M5-brane suspended between the two M9 brane boundaries, for which we find the asymptotic heterotic supergravity solution. PMID- 17280194 TI - How can we test the neutrino mass seesaw mechanism experimentally? AB - The seesaw mechanism for the small neutrino mass has been a popular paradigm, yet it has been believed that there is no way to test it experimentally. We present a conceivable outcome from future experiments that would convince us of the seesaw mechanism. It would involve data from the CERN Large Hadron Collider, International Linear Collider, cosmology, underground, and low-energy flavor experiments to establish the case. PMID- 17280196 TI - J/psi production in quark-gluon plasma. AB - We study J/psi production at RHIC and LHC energies with both initial production at energies reached and the BNL Relativistic Heavy Ion Collider (RHIC) and CERN Large Hadron Collider (LHC) with regeneration. We solve the coupled set of transport equations for the J/psi distribution in phase space and the hydrodynamic equation for evolution of quark-gluon plasma. At RHIC, continuous regeneration is crucial for the J/psi momentum distribution while the elliptic flow is still dominated by initial production. At energies reached at the LHC energy, almost all the initially created J/psis are dissociated in the medium and regeneration dominates the J/psi properties. PMID- 17280197 TI - Q values of the superallowed beta emitters 26Alm, 42Sc, and 46V and their impact on Vud and the unitarity of the Cabibbo-Kobayashi-Maskawa matrix. AB - The beta-decay Q(EC) values of the superallowed beta emitters 26Alm, 42Sc, and 46V have been measured with a Penning trap to a relative precision of better than 8 x 10(-9). Our result for 46V, 7052.72(31) keV, confirms a recent measurement that differed from the previously accepted reaction-based Q(EC) value. However, our results for 26Alm and 42Sc, 4232.83(13) keV and 6426.13(21) keV, are consistent with previous reaction-based values. By eliminating the possibility of a systematic difference between the two techniques, this result demonstrates that no significant shift in the deduced value of Vud should be anticipated. PMID- 17280198 TI - Cancellation of stark shifts in optical lattice clocks by use of pulsed Raman and electromagnetically induced transparency techniques. AB - We propose a combination of electromagnetically induced transparency-Raman and pulsed spectroscopy techniques to accurately cancel frequency shifts arising from electromagnetically induced transparency fields in forbidden optical clock transitions of alkaline earth atoms. At appropriate detunings, time-separated laser pulses are designed to trap atoms in coherent superpositions while eliminating off-resonance ac Stark contributions, achieving efficient population transfer up to 60% with inaccuracy <10(-17). Results from the wave-function formalism are confirmed by the density matrix approach. PMID- 17280199 TI - Experimental verification of minima in excited long-range Rydberg states of Rb2. AB - Recent theoretical studies with alkali atoms A* excited to high Rydberg states predicted the existence of ultra-long-range molecular bound states. Such excited dimers have large electric dipole moments which, in combination with their long radiative lifetimes, make them excellent candidates for manipulation in applications. This Letter reports on experimental investigations of the self broadening of Rb principal series lines, which revealed multiple satellites in the line wings. The positions of the satellites agree quantitatively with theoretically predicted minima in the excited long-range Rydberg states of Rb2. PMID- 17280200 TI - Double ionization of lithiumlike ions by Compton scattering of high-energy photons. AB - The double ionization of lithiumlike ions by Compton scattering of photons is investigated in the asymptotic high-energy region. To leading order of the nonrelativistic perturbation theory, the total cross section for double Compton effect is calculated, taking into account the channels of simultaneous and sequential emission of two electrons. Relationships between the cross sections for double ionization of He- and Li-like ions with the same nuclear charge Z are established. This can open wide perspectives for experimental investigations of ionization processes involving low-lying excited states. The universal scaling is found for the ratio of double-to-single ionization in the lithium isoelectronic sequence. PMID- 17280201 TI - Enantiospecific adsorption of chiral molecules on chiral gold clusters. AB - Enantioselectivity in gold clusters is investigated by studying the adsorption of a chiral amino acid (cysteine) on a chiral Au55 cluster using density functional calculations. The highest adsorption energies were found when the amino and thiolate functional groups of cysteine are bonded to the lowest coordinated edges of the chiral cluster. Enantiospecific adsorption is primarily obtained from the different bond location and strength, at the cluster edge, of the carboxyl groups forming the left- and right-handed enantiomers. These results provide theoretical support to convey enantioselectivity in asymmetric nanocatalysts using chiral gold clusters. PMID- 17280202 TI - Slow-light optical bullets in arrays of nonlinear Bragg-grating waveguides. AB - We demonstrate that propagation direction and velocity of optical pulses can be controlled independently in the structures with multiscale modulation of the refractive index in transverse and longitudinal directions. We reveal that, in arrays of waveguides with phase-shifted Bragg gratings, the refraction angle does not depend on the speed of light, allowing for efficient spatial steering of slow light. In this system, both spatial diffraction and temporal dispersion can be designed independently, and we identify the possibility for self-collimation of slow light when spatial diffraction is suppressed for certain propagation directions. We also show that broadening of pulses in space and time can be eliminated in nonlinear media, supporting the formation of slow-light optical bullets that remain localized irrespective of propagation direction. PMID- 17280203 TI - Evolution of the correlation between orthogonal polarization patterns in broad area lasers. AB - We measure polarization-resolved instantaneous patterns in a large-aspect ratio quasi-isotropic Nd:YAG laser. High correlation between the instantaneous orthogonal polarization patterns recorded at the earlier stages of the laser pulse has been found due to the strong cross saturation between both polarization modes. PMID- 17280204 TI - Hyperboloid structures formed by polarization singularities in coherent vector fields with longitudinal-transverse coupling. AB - The propagation-dependent polarization vector fields are experimentally created from an isotropic microchip laser with a longitudinal-transverse coupling and entanglement of the polarization states. The experimental three-dimensional coherent vector fields are analytically reconstructed with a coherent superposition of orthogonal circularly polarized vortex modes. Each polarized component is found to comprise two Laguerre-Gaussian modes with different topological charges. With the analytical representation, the polarization singularities, on which the electric polarization ellipse is purely circular (C lines) or purely linear (L surfaces), are explored. The C line singularities are found to form an intriguing hyperboloidal structure. PMID- 17280205 TI - Modulational instability in a layered Kerr medium: theory and experiment. AB - We present the first experimental investigation of modulational instability in a layered Kerr medium. The particularly interesting and appealing feature of our configuration, consisting of alternating glass-air layers, is the piecewise constant nature of the material properties, which allows a theoretical linear stability analysis leading to a Kronig-Penney equation whose forbidden bands correspond to the modulationally unstable regimes. We find very good quantitative agreement between theoretical, numerical, and experimental diagnostics of the modulational instability. Because of the periodicity in the evolution variable arising from the layered medium, there are multiple instability regions rather than just one as in a uniform medium. PMID- 17280206 TI - Unified Green's function retrieval by cross correlation. AB - It has been shown by many authors that the cross correlation of two recordings of a diffuse wave field at different receivers yields the Green's function between these receivers. Recently the theory has been extended for situations where time reversal invariance does not hold (e.g., in attenuating media) and where source receiver reciprocity breaks down (in moving fluids). Here we present a unified theory for Green's function retrieval that captures all these situations and, because of the unified form, readily extends to more complex situations, such as electrokinetic Green's function retrieval in poroelastic or piezoelectric media. The unified theory has a wide range of applications in "remote sensing without a source." PMID- 17280207 TI - Mechanism of polymer drag reduction using a low-dimensional model. AB - Using a retarded-motion expansion to describe the polymer stress, we derive a low dimensional model to understand the effects of polymer elasticity on the self sustaining process that maintains the coherent wavy streamwise vortical structures underlying wall-bounded turbulence. Our analysis shows that at small Weissenberg numbers, Wi, elasticity enhances the coherent structures. At higher Wi, however, polymer stresses suppress the streamwise vortices (rolls) by calming down the instability of the streaks that regenerates the rolls. We show that this behavior can be attributed to the nonmonotonic dependence of the biaxial extensional viscosity on Wi, and identify it as the key rheological property controlling drag reduction. PMID- 17280209 TI - Evidence of relaxation and spontaneous transition to a high-confinement state in high-beta steady-state plasmas sustained by rotating magnetic fields. AB - Evidence of relaxation has appeared, for the first time, in the extremely high beta, steady-state field-reversed configuration plasma states driven by rotating magnetic fields (RMF) in the translation, confinement, and sustainment experiment. The plasma self-organizes into a near-force-free state in the vicinity of the magnetic axis, with significant improvement in confinement. Associated with this change in magnetic topology is the appearance of an axial RMF component; this would, in turn, generate a current drive in the poloidal direction, thus sustaining the magnetic helicity. A newly developed two dimensional "equilibrium-lite" model is employed to analyze the magnetic properties of the final high-confinement state, and shows a large q and a significant magnetic shear in the core. PMID- 17280208 TI - Collisional relaxation of superthermal electrons generated by relativistic laser pulses in dense plasma. AB - Energy relaxation of the hot electron population generated by relativistic laser pulses in overdense plasma is analyzed for densities ranging from below to 1000 times solid density. It is predicted that longitudinal beam-plasma instabilities, which dominate energy transfer between hot electrons and plasma at lower densities, are suppressed by collisions beyond solid density. The respective roles of collisional energy transfer modes, i.e., direct collisions, diffusion, and resistive return current heating, are identified with respect to plasma density. The transition between the kinetic and the collisional regimes and scalings of collisional process are demonstrated by a fully integrated one dimensional collisional particle simulation. PMID- 17280211 TI - Spin incommensurability and two phase competition in cobaltites. AB - The perovskite LaCoO3 evolves from a nonmagnetic Mott insulator to a spin cluster ferromagnet (FM) with the substitution of Sr2+ for La3+ in La1-xSrxCoO3. The clusters increase in size and number with x and the charge percolation through the clusters leads to a metallic state. Using elastic neutron scattering on La1 xSrxCoO3 single crystals, we show that an incommensurate spin superstructure coexists with the FM spin clusters. The incommensurability increases continuously with x, with the intensity rising in the insulating phase and dropping in the metallic phase as it directly competes with the commensurate FM, itinerant clusters. The spin incommensurability arises from local order of Co3+-Co4+ clusters but no long-range static or dynamic spin stripes develop. The coexistence and competition of the two magnetic phases explain the residual resistivity at low temperatures in samples with metalliclike transport. PMID- 17280210 TI - Observation of spontaneous toroidal rotation inversion in Ohmically heated Tokamak plasmas. AB - Bulk plasma toroidal rotation is observed to invert spontaneously from counter to cocurrent direction in TCV (Tokamak a Configuration Variable) Ohmically heated discharges, in low confinement mode, without momentum input. The inversion occurs in high current discharges, when the plasma electron density exceeds a well defined threshold. The transition between the two rotational regimes has been studied by means of density ramps. The results provide evidence of a change of the balance of nondiffusive momentum fluxes in the core of a plasma without an external drive. PMID- 17280212 TI - X-ray Bragg diffraction in asymmetric backscattering geometry. AB - We observe three effects in the Bragg diffraction of x rays in backscattering geometry from asymmetrically cut crystals. First, exact Bragg backscattering takes place not at normal incidence to the reflecting atomic planes. Second, a well-collimated (approximately 1 microrad) beam is transformed after the Bragg reflection into a strongly divergent beam (230 microrad) with reflection angle dependent on x-ray wavelength--an effect of angular dispersion. The asymmetrically cut crystal thus behaves like an optical prism, dispersing an incident collimated polychromatic beam. The dispersion rate is approximately 8.5 mrad/eV. Third, parasitic Bragg reflections accompanying Bragg backreflection are suppressed. These effects offer a radically new means for monochromatization of x rays not limited by the intrinsic width of the Bragg reflection. PMID- 17280213 TI - Tricritical phenomena at the gamma-->alpha transition in Ce0.9-xLaxTh0.1 alloys. AB - The gamma-->alpha isostructural transition in the Ce0.9-xLaxTh0.1 system is measured as a function of La alloying using specific heat, magnetic susceptibility, resistivity, thermal expansivity or striction measurements. A line of discontinuous transitions, as indicated by the change in volume, decreases exponentially from 118 K to close to 0 K with increasing La doping, and the transition changes from being first-order to continuous at a critical concentration, x(c) approximately 0.14. At the tricritical point, the coefficient of the linear T term in the specific heat gamma and the magnetic susceptibility increase rapidly near x(c) and approach large values at x=0.35 signifying that a heavy Fermi-liquid state evolves at large doping. The Wilson ratio reaches a value above 2 for a narrow range of concentrations near x(c), where the specific heat and susceptibility vary most rapidly with the doping concentration. PMID- 17280214 TI - Quantum Monte Carlo simulation of the high-pressure molecular-atomic crossover in fluid hydrogen. AB - A first-order liquid-liquid phase transition in high-pressure hydrogen between molecular and atomic fluid phases has been predicted in computer simulations using ab initio molecular dynamics approaches. However, experiments indicate that molecular dissociation may occur through a continuous crossover rather than a first-order transition. Here we study the nature of molecular dissociation in fluid hydrogen using an alternative simulation technique in which electronic correlation is computed within quantum Monte Carlo methods, the so-called coupled electron-ion Monte Carlo method. We find no evidence for a first-order liquid liquid phase transition. PMID- 17280216 TI - Kinetic instabilities in the growth of one dimensional molecular nanostructures. AB - We develop a theory for the growth of one dimensional (1D) chains stabilized by anisotropic interactions, such as hydrogen bonding. Molecular chains are nucleated, grow, and may then undergo a kinetically driven transition to a two dimensional morphology. Kinetic Monte Carlo simulations show that extended 1D growth occurs between two temperature limits determined by two distinct kinetic instabilities. The limiting temperatures depend on interaction strength and deposition rate and, for a certain parameter range, 1D growth is completely suppressed. PMID- 17280215 TI - Motion of nanodroplets near edges and wedges. AB - Nanodroplets residing near wedges or edges of solid substrates exhibit a disjoining pressure induced dynamics. Our nanoscale hydrodynamic calculations reveal that nonvolatile droplets are attracted or repelled from edges or wedges depending on details of the corresponding laterally varying disjoining pressure generated, e.g., by a possible surface coating. PMID- 17280195 TI - Observation of an excited charm baryon Omega c* decaying to Omega c0gamma. AB - We report the first observation of an excited singly charmed baryon Omega c* (css) in the radiative decay Omega c0gamma, where the Omega c0 baryon is reconstructed in the decays to the final states Omega(-)pi+, Omega(-)pi+pi0, Omega(-)pi+pi(-)pi+, and Xi(-)K(-)pi+pi+. This analysis is performed using a data set of 230.7 fb(-1) collected by the BABAR detector at the PEP-II asymmetric energy B factory at the Stanford Linear Accelerator Center. The mass difference between the Omega c* and the Omega c0 baryons is measured to be 70.8+/ 1.0(stat)+/-1.1(syst) MeV/c2. We also measure the ratio of inclusive production cross sections of Omega c* and Omega c0 in e+e(-) annihilation. PMID- 17280217 TI - Anomalous Fermi-surface dependent pairing in a self-doped high-Tc superconductor. AB - We report the discovery of a self-doped multilayer high Tc superconductor Ba2Ca3Cu4O8F2 (F0234) which contains distinctly different superconducting gap magnitudes along its two Fermi-surface sheets. While formal valence counting would imply this material to be an undoped insulator, it is a self-doped superconductor with a Tc of 60 K, possessing simultaneously both electron- and hole-doped Fermi-surface sheets. Intriguingly, the Fermi-surface sheet characterized by the much larger gap is the electron-doped one, which has a shape disfavoring two electronic features considered to be important for the pairing mechanism: the van Hove singularity and the antiferromagnetic (pi/a, pi/a) scattering. PMID- 17280218 TI - Lande g tensor in semiconductor nanostructures. AB - Understanding the electronic structure of semiconductor nanostructures is not complete without a detailed description of their corresponding spin-related properties. Here we explore the response of the shell structure of InAs self assembled quantum dots to magnetic fields oriented in several directions, allowing mapping of the g-tensor modulus for the s and p shells. We find that the g tensors for the s and p shells exhibit a very different behavior. The s state, being more localized, probes the confinement potential details by sweeping the magnetic-field orientation from the growth direction towards the in-plane direction. For the p state, the g-tensor modulus is closer to that of the surrounding GaAs, consistent with a larger delocalization. In addition to the assessment of the g tensor, these results reveal further details of the confining potentials of self-assembled quantum dots that have not yet been probed. PMID- 17280220 TI - Exact SU(2) symmetry and persistent spin helix in a spin-orbit coupled system. AB - Spin-orbit coupled systems generally break the spin rotation symmetry. However, for a model with equal Rashba and Dresselhauss coupling constants, and for the [110] Dresselhauss model, a new type of SU(2) spin rotation symmetry is discovered. This symmetry is robust against spin-independent disorder and interactions and is generated by operators whose wave vector depends on the coupling strength. It renders the spin lifetime infinite at this wave vector, giving rise to a persistent spin helix. We obtain the spin fluctuation dynamics at, and away from, the symmetry point and suggest experiments to observe the persistent spin helix. PMID- 17280221 TI - Spatially dependent Kondo effect in quantum corrals. AB - We study the Kondo screening of a single magnetic impurity inside a nonmagnetic quantum corral located on the surface of a metallic host system. We show that the spatial structure of the corral's eigenmodes leads to a spatially dependent Kondo effect whose signatures are spatial variations of the Kondo temperature T K. Moreover, we predict that the Kondo screening is accompanied by the formation of multiple Kondo resonances with characteristic spatial patterns. Our results open new possibilities to manipulate and explore the Kondo effect by using quantum corrals. PMID- 17280219 TI - Superconducting PrOs4Sb12: a thermal conductivity study. AB - The superconducting state of the heavy fermion PrOs4Sb12 is studied by heat transport measurements on a highly homogeneous single crystal exhibiting only one transition peak in the specific heat. The field and temperature dependence of the thermal conductivity confirm multiband superconductivity and point to fully open gaps on the whole Fermi surface. PMID- 17280222 TI - Effect of disorder on transport in graphene. AB - Quenched disorder in graphene is characterized by 5 constants and experiences the logarithmic renormalization even from the spatial scales smaller than the Fermi wavelength. We derive and solve renormalization group equations (RGEs) describing the system at such scales. At larger scales, we derive a nonlinear supermatrix sigma model completely describing localization and crossovers between different ensembles. The parameters of this sigma model are determined by the solutions of the RGEs. PMID- 17280223 TI - Low-energy theory of disordered graphene. AB - At low values of external doping, graphene displays a wealth of unconventional transport properties. Perhaps most strikingly, it supports a robust "metallic" regime, with universal conductance of the order of the conductance quantum. We here apply a combination of mean-field and bosonization methods to explore the large scale transport properties of the system. We find that, irrespective of the doping level, disordered graphene is subject to the common mechanisms of Anderson localization. However, at low doping a number of renormalization mechanisms conspire to protect the conductivity of the system, to an extend that strong localization may not be seen even at temperatures much smaller than those underlying present experimental work. PMID- 17280224 TI - Fractional charges and quantum phase transitions in imbalanced bilayer quantum Hall systems. AB - We extend the composite boson theory to study slightly imbalanced bilayer quantum Hall systems. In the global U(1) symmetry breaking excitonic superfluid side, as the imbalance increases, the system supports continuously changing fractional charges. In the translational symmetry breaking pseudospin density wave (PSDW) side, there are two quantum phase transitions from the commensurate PSDW to an incommensurate PSDW and then to the excitonic superfluid state. We compare our theory with experimental data and also the previous microscopic calculations. PMID- 17280225 TI - Real-space imaging of alternate localization and extension of quasi-two dimensional electronic States at graphite surfaces in magnetic fields. AB - We measured the local density of states (LDOS) of a quasi-two-dimensional (2D) electron system near point defects on a surface of highly oriented pyrolytic graphite with scanning tunneling microscopy and spectroscopy. Differential tunnel conductance images taken at very low temperatures and in high magnetic fields show a clear contrast between localized and extended spatial distributions of the LDOS at the valley and peak energies of the Landau level spectrum, respectively. The localized electronic state has a single circular distribution around the defects with a radius comparable to the magnetic length. The localized LDOS is in good agreement with a spatial distribution of a calculated wave function for a single electron in 2D in a Coulomb potential in magnetic fields. PMID- 17280226 TI - Quantum spin Hall effect and enhanced magnetic response by spin-orbit coupling. AB - We show that the spin-Hall conductivity in insulators is related to a magnetic susceptibility representing the strength of the spin-orbit coupling. We use this relationship as a guiding principle to search real materials showing quantum spin Hall effect. As a result, we theoretically predict that two-dimensional bismuth will show the quantum spin-Hall effect, both by calculating the helical edge states, and by showing the nontriviality of the Z2 topological number, and propose possible experiments. PMID- 17280228 TI - Electron transport in stretched monoatomic gold wires. AB - The conductance of monoatomic gold wires containing 3-7 gold atoms has been obtained from ab initio calculations. The transmission is found to vary significantly depending on the wire stretching and the number of incorporated atoms. Such oscillations are determined by the electronic structure of the one dimensional (1D) part of the wire between the contacts. Our results indicate that the conductivity of 1D wires can be suppressed without breaking the contact. PMID- 17280229 TI - Nonequilibrium quantum criticality in open electronic systems. AB - A theory is presented of quantum criticality in open (coupled to reservoirs) itinerant-electron magnets, with nonequilibrium drive provided by current flow across the system. Both departures from equilibrium at conventional (equilibrium) quantum critical points and the physics of phase transitions induced by the nonequilibrium drive are treated. Nonequilibrium-induced phase transitions are found to have the same leading critical behavior as conventional thermal phase transitions. PMID- 17280227 TI - Local spectroscopy of image-potential-derived states: from single molecules to monolayers of benzene on Cu(111). AB - Stark-shifted image-potential states were measured with an STM tip for benzene adsorbed on a Cu(111) surface. A single benzene molecule locally shifts the position of the first image state toward the Fermi level by 0.2 eV relative to its position on the clean surface. The energetic position of this molecule modified state shifts to lower energy with increasing coverage of benzene on the surface. This is attributed to local surface potential changes that are correlated with the lowering of the crystal work function due to adsorption of benzene. PMID- 17280230 TI - Quantum-well wave-function localization and the electron-phonon interaction in thin Ag nanofilms. AB - The electron-phonon interaction in thin Ag nanofilms epitaxially grown on Cu(111) is investigated by temperature-dependent and angle-resolved photoemission from silver quantum-well states. Clear oscillations in the electron-phonon coupling parameter as a function of the silver film thickness are observed. Different from other thin film systems where quantum oscillations are related to the Fermi-level crossing of quantum-well states, we can identify a new mechanism behind these oscillations, based on the wave-function localization of the quantum-well states in the film. PMID- 17280231 TI - Dynamic coupling-decoupling crossover in the current-driven vortex state in Tl2Ba2CaCu2O8 probed by the Josephson plasma resonance. AB - We have used terahertz spectroscopy to measure the Josephson plasma resonance in the superconductor Tl2Ba2CaCu2O8+delta. This allows us to probe the longitudinal ordering of pancake vortices as a function of applied ab-plane current in a 2.5 kG c-axis magnetic field. With increasing current in the low temperature vortex solid phase, we observe a decrease in the interlayer phase coherence consistent with a progressive misalignment of the pancake vortices in neighboring layers. In the high temperature vortex liquid phase, an increase in the longitudinal ordering occurs above a certain threshold current. Our results show evidence of a current-driven coupling-decoupling crossover in the pinned liquid phase. PMID- 17280232 TI - Magnetic response of mesoscopic superconducting rings with two order parameters. AB - The magnetic response and fluxoid transitions of superconducting aluminum rings of various sizes, deposited under conditions likely to generate a layered structure, show good agreement with a two-order-parameter Ginzburg-Landau model. For intermediate couplings, we find metastable states that have different phase winding numbers around the ring in each of the two order parameters. Those states, previously theoretically predicted, are analogous to fractional vortices in singly connected samples with two-order-parameter superconductivity. Larger coupling locks the relative phase so that the two order parameters are only manifest in the temperature dependence of the response. With increasing proximitization, this signature gradually disappears. PMID- 17280233 TI - Nonlocal correlations in normal-metal superconducting systems. AB - We examine nonlocal effects between normal-metal gold probes connected by superconducting aluminum. For highly transparent Au/Al interfaces, we find nonlocal voltages that obey a spatial and temperature evolution distinct from the nonequilibrium charge imbalance signals usually found in such systems. These voltages are consistent with the predicted effects of crossed Andreev reflection and elastic cotunneling, effects that involve coherent correlations between spatially separated electrons. PMID- 17280234 TI - Rotational symmetry breaking in the ground state of sodium-doped cuprate superconductors. AB - We use an extended t-J model to study a single hole bound to a Na+ acceptor in Ca2-xNaxCuO2Cl2. For parameters suitable to cuprates, the ground state has a twofold degeneracy, corresponding to even (odd) reflection symmetry around the x (y) axes. The conductance pattern of the broken symmetry state is anisotropic as the tip of a tunneling microscope scans above the Cu-O-Cu bonds along the x (y) axes. This anisotropy is pronounced at lower voltages but reduced at higher voltages. Our theory agrees qualitatively with recent data of scanning tunneling microscopy showing broken local rotational symmetry. PMID- 17280235 TI - Composite to tilted vortex lattice transition in Bi2Sr2CaCu2O8+delta in oblique fields. AB - Precision measurements of the vortex phase diagram in single crystals of the layered superconductor Bi2Sr2CaCu2O8+delta in oblique magnetic fields confirm the existence of a second phase transition, in addition to the usual first-order vortex-lattice melting line Hm(T). The transition has a strong first-order character, is accompanied by strong hysteresis, and intersects the melting line in a tricritical point (Hm perpendicular, Hcr parallel). Its field dependence and the changing character of the melting line at the tricritical point strongly suggest that the ground state for magnetic fields closely aligned with the superconducting layers is a lattice of uniformly tilted vortex lines. PMID- 17280236 TI - Interaction-induced renormalization of Andreev reflection. AB - We analyze the charge transport between a one-dimensional weakly interacting electron gas and a superconductor within the scaling approach in the basis of scattering states. We derive the renormalization group equations, which fully account for the intrinsic energy dependence due to Andreev reflection. A strong renormalization of the corresponding reflection phase is predicted even for a perfectly transparent metal-superconductor interface. The interaction-induced suppression of the Andreev conductance is shown to be highly sensitive to the normal-state resistance, providing a possible explanation of experiments with carbon-nanotube/superconductor junctions by Morpurgo et al. [Science 286, 263 (1999)]. PMID- 17280237 TI - Probing tiny motions of nanomechanical resonators: classical or quantum mechanical? AB - We propose a spectroscopic approach to probe tiny vibrations of a nanomechanical resonator (NAMR), which may reveal classical or quantum behavior depending on the decoherence-inducing environment. Our proposal is based on the detection of the voltage-fluctuation spectrum in a superconducting transmission line resonator (TLR), which is indirectly coupled to the NAMR via a controllable Josephson qubit acting as a quantum transducer. The classical (quantum mechanical) vibrations of the NAMR induce symmetric (asymmetric) Stark shifts of the qubit levels, which can be measured by the voltage fluctuations in the TLR. Thus, the motion of the NAMR, including if it is quantum mechanical or not, could be probed by detecting the voltage-fluctuation spectrum of the TLR. PMID- 17280238 TI - Clustering in a precipitate-free GeMn magnetic semiconductor. AB - We present the first study relating structural parameters of precipitate-free Ge0.95Mn0.05 films to magnetization data. Nanometer-sized clusters--areas with increased Mn content on substitutional lattice sites compared to the host matrix- are detected in transmission electron microscopy analysis. The films show no overall spontaneous magnetization at all down to 2 K. The TEM and magnetization results are interpreted in terms of an assembly of superparamagnetic moments developing in the dense distribution of clusters. Each cluster individually turns ferromagnetic below an ordering temperature which depends on its volume and Mn content. PMID- 17280239 TI - Induced random fields in the LiHoxY1-xF4 quantum Ising magnet in a transverse magnetic field. AB - The LiHoxY1-xF4 magnetic material in a transverse magnetic field Bx x perpendicular to the Ising spin direction has long been used to study tunable quantum phase transitions in a random disordered system. We show that the Bx induced magnetization along the x direction, combined with the local random dilution-induced destruction of crystalline symmetries, generates, via the predominant dipolar interactions between Ho3+ ions, random fields along the Ising z direction. This identifies LiHoxY1-xF4 in Bx as a new random field Ising system. The random fields explain the rapid decrease of the critical temperature in the diluted ferromagnetic regime and the smearing of the nonlinear susceptibility at the spin-glass transition with increasing Bx and render the Bx induced quantum criticality in LiHoxY1-xF4 likely inaccessible. PMID- 17280240 TI - Unusual evolution of the conduction-electron state in CexLa1-xB6 from non-Fermi liquid to Fermi liquid. AB - We report unusual evolution of the conduction-electron state in the localized f electron system CexLa1-xB6 from normal electron state to heavy Fermi liquid (FL) state through local FL and non-FL states with increasing Ce concentration and/or with increasing magnetic field. The effective mass of quasiparticle or the coefficient A of T2 term of resistivity is found to increase divergently near the boundary between FL state and non-FL state. The features of the non-FL state are also different from those of the typical non-FL systems previously observed or theoretically predicted. PMID- 17280241 TI - Anomalous bias dependence of spin torque in magnetic tunnel junctions. AB - We predict an anomalous bias dependence of the spin transfer torque parallel to the interface, Tparallel, in magnetic tunnel junctions, which can be selectively tuned by the exchange splitting. It may exhibit a sign reversal without a corresponding sign reversal of the bias or even a quadratic bias dependence. We demonstrate that the underlying mechanism is the interplay of spin currents for the ferromagnetic (antiferromagnetic) configurations, which vary linearly (quadratically) with bias, respectively, due to the symmetric (asymmetric) nature of the barrier. The spin transfer torque perpendicular to interface exhibits a quadratic bias dependence. PMID- 17280242 TI - Converting Wannier into Frenkel excitons in an inorganic/organic hybrid semiconductor nanostructure. AB - Electronic coupling between Wannier and Frenkel excitons in an inorganic/organic semiconductor hybrid structure is experimentally observed. Time-resolved photoluminescence and excitation spectroscopy directly demonstrate that electronic excitation energy can be transferred with an efficiency of up to 50% from an inorganic ZnO quantum well to an organic [2,2-p-phenylenebis-(5 phenyloxazol), alpha-sexithiophene] overlayer. The coupling is mediated via dipole-dipole-interaction analog to the Forster transfer in donor-acceptor systems. PMID- 17280243 TI - Enhanced fluorescence intermittency of CdSe-ZnS quantum-dot clusters. AB - Fluorescence intermittency, or blinking, of individual close-packed clusters containing two or more CdSe-ZnS quantum dots (QDs) was investigated. The QD clusters exhibited rapid, intense blinking that was distinct from that of isolated QDs blinking independently. This enhanced blinking is suggested to occur when the QDs in the cluster become electronically coupled. The nature of this coupling is not known, though electrons trapped from QDs when they blink off may play a role by altering the electronic environment of neighboring QDs and enhancing their fluorescence properties. PMID- 17280244 TI - Multiphoton ionization in dielectrics: comparison of circular and linear polarization. AB - Ionization mechanisms in bulk dielectrics irradiated by single intense 50-fs laser pulses are investigated by ultrafast time-resolved imaging interferometry. Polarization-sensitive 6-photon ionization is shown to be the dominant ionization mechanism in fused silica and sapphire at intensities around 10 TW/cm2. For both materials the cross sections of 6-photon ionization are found to be significantly higher for linear polarization than for circular. Our experimental results corroborate an earlier theoretical prediction on the dominance of linear polarization in high-order multiphoton ionization. PMID- 17280245 TI - Quantized electron accumulation states in indium nitride studied by angle resolved photoemission spectroscopy. AB - Electron accumulation states in InN have been measured using high resolution angle-resolved photoemission spectroscopy (ARPES). The electrons in the accumulation layer have been discovered to reside in quantum well states. ARPES was also used to measure the Fermi surface of these quantum well states, as well as their constant binding energy contours below the Fermi level E(F). The energy of the Fermi level and the size of the Fermi surface for these quantum well states could be controlled by varying the method of surface preparation. This is the first unambiguous observation that electrons in the InN accumulation layer are quantized and the first time the Fermi surface associated with such states has been measured. PMID- 17280246 TI - Signatures of short-range many-body effects in the dielectric function of silicon for finite momentum transfer. AB - We present an investigation of the dynamic structure factor and of the dielectric function epsilonM(Q,omega) of the prototypical semiconductor silicon for finite momentum transfer, combining inelastic x-ray scattering experiments and ab initio calculations. In contrast with optical spectra, for finite momentum transfer time dependent density-functional theory in the adiabatic local-density approximation together with lifetime broadening describes the physics of valence excitations correctly. Major structures in the spectra, governed by short-range crystal and exchange-correlation local-field effects, are strongly influenced by a mixing of transitions of positive and negative energies, in striking difference to spectra for vanishing momentum transfer. This mixing gives rise to a pronounced Fano asymmetry. PMID- 17280247 TI - Entropy-driven formation of the gyroid cubic phase. AB - We show, by computer simulation, that tapered or pear-shaped particles, interacting through purely repulsive interactions, can freely self-assemble to form the three-dimensionally periodic, gyroid cubic phase. The Ia3d gyroid cubic phase is formed by these particles on both compression of an isotropic configuration and expansion of a smectic A bilayer arrangement. For the latter case, it is possible to identify the steps by which the topological transformation from nonintersecting planes to fully interpenetrating, periodic networks takes place. PMID- 17280248 TI - Modifications of the mesoscopic structure of cellulose in paper degradation. AB - Paper is the main component of a huge quantity of cultural heritage. It is primarily composed of cellulose that undergoes significant degradation with the passage of time. By using small angle neutron scattering (SANS), we investigated cellulose's supramolecular structure, which allows access to degradation agents, in ancient and modern samples. For the first time, SANS data were interpreted in terms of water-filled pores, with their sizes increasing from 1.61 nm up to 1.97 nm in natural and artificially aged papers. The protective effect of gelatine sizing was also observed. PMID- 17280249 TI - Double coherence resonance in neuron models driven by discrete correlated noise. AB - We study the influence of correlations among discrete stochastic excitatory or inhibitory inputs on the response of the FitzHugh-Nagumo neuron model. For any level of correlation, the emitted signal exhibits at some finite noise intensity a maximal degree of regularity, i.e., a coherence resonance. Furthermore, for either inhibitory or excitatory correlated stimuli, a double coherence resonance is observable. Double coherence resonance refers to a (absolute) maximum coherence in the output occurring for an optimal combination of noise variance and correlation. All of these effects can be explained by taking advantage of the discrete nature of the correlated inputs. PMID- 17280250 TI - Transient ordered domains in single-component phospholipid bilayers. AB - We report evidence of dense, ordered nanodomains in single-component fluid lipid bilayers. Our atomic-scale molecular dynamics simulations suggest that the area available to a lipid acyl chain exhibits large fluctuations, resulting in denser and sparser domains. The sizes of the dense domains can be up to approximately 10 nm, and their lifetimes are of the order of approximately 10 ns. In addition, our simulations suggest that domains of lipids with highly ordered acyl chains form predominantly within the dense regions, their sizes ranging from a few chains up to a few nanometers, and with lifetimes between approximately 10 ps-10 ns. These observations shed light on the origin of experimentally observed fluctuations, as well as on the mechanisms of phase transitions in lipid membranes. PMID- 17280251 TI - Hierarchical organization unveiled by functional connectivity in complex brain networks. AB - How do diverse dynamical patterns arise from the topology of complex networks? We study synchronization dynamics in the cortical brain network of the cat, which displays a hierarchically clustered organization, by modeling each node (cortical area) with a subnetwork of interacting excitable neurons. We find that in the biologically plausible regime the dynamics exhibits a hierarchical modular organization, in particular, revealing functional clusters coinciding with the anatomical communities at different scales. Our results provide insights into the relationship between network topology and functional organization of complex brain networks. PMID- 17280252 TI - Origin of the slow dynamics and the aging of a soft glass. AB - We study by light microscopy a soft glass consisting of a compact arrangement of polydisperse multilamellar vesicles. We show that its slow and nonstationary dynamics results from the unavoidable small fluctuations of temperature, which induce intermittent local shear deformations in the sample, because of thermal expansion and contraction. Temperature-induced shear provokes both reversible and irreversible rearrangements whose amplitude decreases with time, leading to an exponential slowing down of the dynamics with sample age. PMID- 17280253 TI - Space-time clustering and correlations of major earthquakes. AB - Earthquake occurrence in nature is thought to result from correlated elastic stresses, leading to clustering in space and time. We show that the occurrence of major earthquakes in California correlates with time intervals when fluctuations in small earthquakes are suppressed relative to the long term average. We estimate a probability of less than 1% that this coincidence is due to random clustering. PMID- 17280254 TI - Comment on "Spin dynamics of the electron-doped high-Tc superconducting cuprates". PMID- 17280256 TI - Spin Hall effects for cold atoms in a light-induced gauge potential. AB - We propose an experimental scheme to observe spin Hall effects with cold atoms in a light-induced gauge potential. Under an appropriate configuration, the cold atoms moving in a spatially varying laser field experience an effective spin dependent gauge potential. Through numerical simulation, we demonstrate that such a gauge field leads to observable spin Hall currents under realistic conditions. We also discuss the quantum spin Hall state in an optical lattice. PMID- 17280257 TI - Observation of vortex pinning in Bose-Einstein condensates. AB - We report the observation of vortex pinning in rotating gaseous Bose-Einstein condensates. Vortices are pinned to columnar pinning sites created by a corotating optical lattice superimposed on the rotating Bose-Einstein condensates. We study the effects of two types of optical lattice: triangular and square. In both geometries we see an orientation locking between the vortex and the optical lattices. At sufficient intensity the square optical lattice induces a structural crossover in the vortex lattice. PMID- 17280258 TI - Anomalously long passage through a rounded-off-step potential due to a new mechanism of multidimensional tunneling. AB - The fully complex domain semiclassical theory based upon the complexified stable unstable manifold theory, which we have developed in our recent studies, is successfully applied to explain anomalous tunneling phenomena numerically observed in a periodically modulated round-off-step potential. Numerical experiments show that tunneling through the oscillating step potential is characterized by a spatially nondecaying tunneling tail and an anomalously slow relaxation. The key is the existence of a critical trajectory exhibiting singular behavior, and the analysis of neighboring trajectories around it reproduces the essence of such anomalous phenomena. PMID- 17280259 TI - Dynamical vortex phases in a Bose-Einstein condensate driven by a rotating optical lattice. AB - We present simulation results of the vortex dynamics in a trapped Bose-Einstein condensate in the presence of a rotating optical lattice. Changing the potential amplitude and the relative rotation frequency between the condensate and the optical lattice, we find a rich variety of dynamical phases of vortices. The onset of these different phases is described by the force balance of a driving force, a pinning force, and vortex-vortex interactions. In particular, when the optical lattice rotates faster than the condensate, an incommensurate effect leads to a vortex-liquid phase supported by the competition between the driving force and the dissipation. PMID- 17280260 TI - Ratcheting up energy by means of measurement. AB - The destruction of quantum coherence can pump energy into a system. For our examples this is paradoxical because the destroyed correlations are ordinarily considered negligible. Mathematically the explanation is straightforward and physically one can identify the degrees of freedom supplying this energy. Nevertheless, the energy input can be calculated without specific reference to those degrees of freedom. PMID- 17280261 TI - Spin-orbit mediated control of spin qubits. AB - We propose to use the spin-orbit interaction as a means to control electron spins in quantum dots, enabling both single-qubit and two-qubit operations. Very fast single-qubit operations may be achieved by temporarily displacing the electrons. For two-qubit operations the coupling mechanism is based on a combination of the spin-orbit coupling and the mutual long-ranged Coulomb interaction. Compared to existing schemes using the exchange coupling, the spin-orbit induced coupling is less sensitive to random electrical fluctuations in the electrodes defining the quantum dots. PMID- 17280262 TI - Force dependence of transition rates in atomic friction. AB - The lateral forces during stick-slip motion of an atomic force microscope cantilever on highly oriented pyrolytic graphite are measured and analyzed. We identify the regimes where thermally activated interstitial hopping of the cantilever tip proceeds according to a single-step reaction scheme and extract the corresponding force-dependent transition rates directly from the experimental data. We find that such a single-step reaction scenario is valid only at relatively high velocities, while at slower pulling speeds, a more complicated hopping mechanism must be at work. We suggest formation of multiple bonds of the tip-sample contact as a possible candidate for this mechanism. PMID- 17280263 TI - Generic quantum ratchet accelerator with full classical chaos. AB - A simple model of quantum ratchet transport that can generate unbounded linear acceleration of the quantum ratchet current is proposed, with the underlying classical dynamics fully chaotic. The results demonstrate that generic quantum ratchet transport can occur with any type of classical phase space structure. The quantum ratchet transport with full classical chaos is also shown to be very robust to noise due to the large linear acceleration afforded by the quantum dynamics. One possible experiment allowing observation of these predictions is suggested. PMID- 17280264 TI - Long-term stability of an area-reversible atom-interferometer Sagnac gyroscope. AB - We report the first demonstration of a matter-wave interference gyroscope that meets both the short-term noise and long-term stability requirements for high accuracy navigation. This performance level resulted from implementation of a novel technique to precisely reverse the input axis of the gyroscope. PMID- 17280265 TI - Coherent development of neutrino flavor in the supernova environment. AB - We calculate coherent neutrino and antineutrino flavor transformation in the supernova environment, for the first time including self-consistent coupling of intersecting neutrino and antineutrino trajectories. For neutrino mass-squared difference /deltam2/ = 3 x 10(-3) eV2 we find that in the normal (inverted) mass hierarchy the more tangentially-propagating (radially-propagating) neutrinos and antineutrinos can initiate collective, simultaneous medium-enhanced flavor conversion of these particles across broad ranges of energy and propagation direction. Accompanying alterations in neutrino and antineutrino energy spectra and fluxes could affect supernova nucleosynthesis and the expected neutrino signal. PMID- 17280266 TI - Sterile neutrinos, dark matter, and pulsar velocities in models with a Higgs singlet. AB - We identify the range of parameters for which the sterile neutrinos can simultaneously explain the cosmological dark matter and the observed velocities of pulsars. To satisfy all cosmological bounds, the relic sterile neutrinos must be produced sufficiently cold. This is possible in a class of models with a gauge singlet Higgs boson coupled to the neutrinos. Sterile dark matter can be detected by the x-ray telescopes. The presence of the singlet in the Higgs sector can be tested at the CERN Large Hadron Collider. PMID- 17280268 TI - Bs-Bs mixing in grand unified models. AB - We study Bs-Bs mixing in supersymmetry grand unified SO(10), SU(5) models where the mixings among the second and third generation squarks arise due to the existence of flavor violating sources in the Dirac and Majorana couplings which are responsible for neutrino mixings. We find that when the branching ratio of tau-->mugamma decay is enhanced to be around the current experimental bound, Bs Bs mixing may also contain large contribution from supersymmetry in the SO(10) boundary condition. Consequently, the phase of Bs-Bs mixing is large (especially for small tanbeta and large scalar mass m0) and can be tested by measuring CP asymmetries of Bs decay modes. PMID- 17280270 TI - Nature of the f0(600) scalar meson from its Nc dependence at two loops in unitarized chiral perturbation theory. AB - By using unitarized two-loop chiral perturbation theory partial waves to describe pion-pion scattering we find that the dominant component of the lightest scalar meson does not follow the qq dependence on the number of colors that, in contrast, is obeyed by the lightest vectors. The method suggests that a subdominant qq component of the f0(600) possibly originates around 1 GeV. PMID- 17280269 TI - Study of decay mechanisms in B--->Lambdac+ppi- decays and observation of low-mass structure in the Lambdac+p system. AB - Using a sample of 152 x 10(6) BB pairs accumulated with the Belle detector at the KEKB e+e- collider, we study the decay mechanism of three-body charmed decay B- - > Lambdac+ ppi-. The intermediate two-body decay B--->Sigmac (2455)0 p is observed for the first time with a branching fraction of (3.7 +/- 0.7 +/- 0.4 +/- 1.0) x 10(-5) and a statistical significance of 8.4sigma. We also observe a low mass enhancement in the (Lambdac+p) system, which can be parametrized as a Breit Wigner function with a mass of (3.35(-0.02)(+0.01) +/-0.02) GeV/c2 and a width of (0.07(-0.03)(+0.04) +/-0.04) GeV/c2. We measure its branching fraction to be (3.9(-0.7)(+0.8) +/- 0.4 +/- 1.0) x 10(-5) with a statistical significance of 6.2sigma. The errors are statistical, systematic, and that of the Lambdac+-->pK- pi+ decay branching fraction. PMID- 17280272 TI - Doubly magic nucleus (108)(270)Hs162. AB - Theoretical calculations predict 270Hs (Z=108, N=162) to be a doubly magic deformed nucleus, decaying mainly by alpha-particle emission. In this work, based on a rapid chemical isolation of Hs isotopes produced in the 26Mg+248Cm reaction, we observed 15 genetically linked nuclear decay chains. Four chains were attributed to the new nuclide 270Hs, which decays by alpha-particle emission with Qalpha=9.02+/-0.03 MeV to 266Sg which undergoes spontaneous fission with a half life of 444(-148)(+444) ms. A production cross section of about 3 pb was measured for 270Hs. Thus, 270Hs is the first nucleus for which experimental nuclear decay properties have become available for comparison with theoretical predictions of the N=162 shell stability. PMID- 17280274 TI - Measurement of the cascade transition via the first excited state of 16O in the 12C(alpha,gamma)16O reaction, and its S factor in stellar helium burning. AB - Radiative alpha-particle capture into the first excited, J(pi)=0+ state of 16O at 6.049 MeV excitation energy has rarely been discussed as contributing to the 12C(alpha,gamma)16O reaction cross section due to experimental difficulties in observing this transition. We report here measurements of this radiative capture in 12C(alpha,gamma)16O for center-of-mass energies of E=2.22 MeV to 5.42 MeV at the DRAGON recoil separator. To determine cross sections, the acceptance of the recoil separator has been simulated in GEANT as well as measured directly. The transition strength between resonances has been identified in R-matrix fits as resulting both from E2 contributions as well as E1 radiative capture. Details of the extrapolation of the total cross section to low energies are then discussed [S6.0(300)=25(-15)(+16) keV b] showing that this transition is likely the most important cascade contribution for 12C(alpha,gamma)16O. PMID- 17280273 TI - Evidence for a three-phonon giant resonance state in 40Ca nuclei. AB - Inelastic scattering of 40Ca on 40Ca at 50 MeV/A has been measured in coincidence with protons at the GANIL facility. The SPEG spectrometer was associated with 240 CsI(Tl) scintillators of the INDRA 4pi array, allowing for the measurement of complete decay events. The missing energy method was applied to these events. For events with excitation energy between 42 and 55 MeV, a direct decay branch by three protons towards the low energy states of 37Cl gives the first evidence for a 3-phonon state built with giant resonances. PMID- 17280275 TI - High-precision calculation of the hyperfine structure of the HD+ ion. AB - High-precision laser spectroscopy of ultracold hydrogen molecular ions has the potential of improving the precision of the electron-to-proton mass ratio. An accurate knowledge of the spin structure of the transition is required in order to permit precise comparison with experimental transition frequencies. We calculate with a relative accuracy of the order of O(alpha2) the hyperfine splitting of the rovibrational states of HD+ with orbital momentum LH+ +S+ + H+, in ultrashort intense laser fields (12 fs, approximately 2 x 10(14) W/cm2) is studied by the coincidence momentum imaging of the three fragment ions. Different electronic and nuclear responses are identified depending on the direction of laser polarization epsilon in the molecular frame. The dependence can be interpreted in terms of the electronic and bonding characters of charge transfer states of H2S coupled to the electronic ground state. PMID- 17280277 TI - Inserting two atoms into a single optical micropotential. AB - We recently demonstrated that strings of trapped atoms inside a standing wave optical dipole trap can be rearranged using optical tweezers [Y. Miroshnychenko, Nature 442, 151 (2006)]. This technique allows us to actively set the interatomic separations on the scale of the individual trapping potential wells. Here, we use such a distance-control operation to insert two atoms into the same potential well. The detected success rate of this manipulation is 16(-3)(+4)%, in agreement with the predictions of a theoretical model based on our experimental parameters. PMID- 17280278 TI - Trace isotope detection enhanced by coherent elimination of power broadening. AB - The selectivity and spectral resolution of traditional laser-based trace isotope analysis, i.e., resonance ionization mass spectrometry (RIMS), is limited by power broadening of the radiative transition. We use the fact that power broadening does not occur in coherently driven quantum systems when the probing and excitation processes are temporally separated to demonstrate significant improvement of trace element detection, even under conditions of strong signals. Specifically, we apply a coherent variant of RIMS to the detection of traces of molecular nitric oxide (NO) isobars. For large laser intensities, the detected isotope signal can be increased by almost 1 order of magnitude without any loss in spectral resolution. PMID- 17280279 TI - Sympathetic cooling of complex molecular ions to millikelvin temperatures. AB - Gas-phase singly protonated organic molecules of mass 410 Da (Alexa Fluor 350) have been cooled from ambient temperature to the hundred millikelvin range by Coulomb interaction with laser-cooled barium ions. The molecules were generated by an electrospray ionization source, transferred to and stored in a radio frequency trap together with the atomic ions. Observations are well described by molecular dynamics simulations, which are used to determine the spatial distribution and thermal energy of the molecules. In one example, an ensemble of 830 laser-cooled 138Ba+ ions cooled 200 molecular ions to less than 115 mK. The demonstrated technique should allow a large variety of protonated molecules to be sympathetically cooled, including molecules of much higher mass, such as proteins. PMID- 17280280 TI - Differential electron emission for single and multiple ionization of argon by 500 eV positrons. AB - Triply differential electron emission cross sections are measured for single ionization of argon by 500 eV positrons. Data are presented for coincidences between projectiles scattered into angles of 3 degrees and electrons with emission energies less than 10 eV that are observed between 45 and 135 degrees along the beam direction. For interpretation, these are compared to cosine squared representations of the binary and recoil lobes which are convoluted over experimental parameters. Singly differential electron emission data for double and triple ionization by positrons are also presented. PMID- 17280281 TI - State-specified protonium formation in low-energy antiproton-hydrogen-atom collisions. AB - We calculate state-specified protonium-formation cross sections in low-energy antiproton-hydrogen-atom collisions by solving the Chew-Goldberger-type integral equation directly instead of integrating the traditional differential scattering equation. Separating the incident wave from the total wave function, we calculate only the scattered outgoing wave propagated by the Green function. The scattering boundary condition is hence automatically satisfied without the tedious procedure of adjusting the wave function at the asymptotic region. The formed protonium atoms tend to be distributed in higher angular momentum l and higher principle quantum number n states as the collision energy increases. The present method has the advantage over the traditional ones in the sense that the required memory size and the computational time are much smaller, and accordingly the problem can be solved with higher accuracy. PMID- 17280282 TI - Properties of resonant interatomic Coulombic decay in Ne dimers. AB - Properties of the interatomic Coulombic decay (ICD) process in Ne dimers have been obtained by tracking the formation of energetic Ne+ ions. The double photoionization cross section, deduced from the Ne+/Ne+ coincidence signal, is dominated by the ICD process and presents a threshold 280 meV below the atomic Ne+2s(-1) threshold. Rydberg excitation of a 2s electron in the dimer creates molecular Rydberg states whose Sigma and Pi symmetries have been resolved. These excited states decay by a resonant ICD process releasing an energetic Ne+ ion and a neutral excited Ne* fragment. Subsequent autoionization of the Ne* fragment explains a double photoionization threshold below the dimer 2s ionization threshold. PMID- 17280283 TI - Minimum uncertainty measurements of angle and angular momentum. AB - We present an accurate description of the conjugate pair angle-angular momentum in terms of the exponential of the angle instead of the angle itself, which leads to dispersion as a natural measure of resolution. Intelligent states minimizing the uncertainty product under the constraint of a given uncertainty in angle or in angular momentum turn out to be given by Mathieu wave functions. We discuss Gaussian approximations to these optimal states in terms of von Mises distributions. The theory is successfully applied to the spatial degrees of freedom of a photon and verified in an experiment that employs computer controlled spatial light modulators at both the state preparation and the analyzing stages. PMID- 17280284 TI - Beyond the Rayleigh criterion: grating assisted far-field optical diffraction tomography. AB - We propose an optical imaging system, in which both illumination and collection are done in far field, that presents a power of resolution better than one-tenth of the wavelength. This is achieved by depositing the sample on a periodically nanostructured substrate illuminated under various angles of incidence. The superresolution is due to the high spatial frequencies of the field illuminating the sample and to the use of an inversion algorithm for reconstructing the map of relative permittivity from the diffracted far field. Thus, we are able to obtain wide-field images with near-field resolution without scanning a probe in the vicinity of the sample. PMID- 17280285 TI - Magnetic plasmon propagation along a chain of connected subwavelength resonators at infrared frequencies. AB - A one-dimensional magnetic plasmon propagating in a linear chain of single split ring resonators is proposed. The subwavelength size resonators interact mainly through exchange of conduction current, resulting in stronger coupling as compared to the corresponding magneto-inductive interaction. Finite-difference time-domain simulations in conjunction with a developed analytical theory show that efficient energy transfer with signal attenuation of less then 0.57 dB/microm and group velocity higher than 1/4c can be achieved. The proposed novel mechanism of energy transport in the nanoscale has potential applications in subwavelength transmission lines for a wide range of integrated optical devices. PMID- 17280286 TI - Emergence of X-shaped spatiotemporal coherence in optical waves. AB - Considering the problem of parametric nonlinear interaction, we report the experimental observation of electromagnetic waves characterized by an X-shaped spatiotemporal coherence; i.e., coherence is neither spatial nor temporal, but skewed along specific spatiotemporal trajectories. The application of the usual, purely spatial or temporal, measures of coherence would erroneously lead to the conclusion that the field is fully incoherent. Such hidden coherence has been identified owing to an innovative diagnostic technique based on simultaneous analysis of both the spatial and temporal spectra. PMID- 17280287 TI - Localized modes in open one-dimensional dissipative random systems. AB - We consider, both theoretically and experimentally, the excitation and detection of the localized quasimodes (resonances) in an open dissipative 1D random system. We show that, even though the amplitude of transmission drops dramatically so that it cannot be observed in the presence of small losses, resonances are still clearly exhibited in reflection. Surprisingly, small losses essentially improve conditions for the detection of resonances in reflection as compared with the lossless case. An algorithm is proposed and tested to retrieve sample parameters and resonance characteristics inside the random system exclusively from reflection measurements. PMID- 17280267 TI - Measurement of the Bs(0) lifetime using semileptonic decays. AB - We report a measurement of the Bs(0) lifetime in the semileptonic decay channel Bs(0) --> Ds- mu+ nuX (and its charge conjugate), using approximately 0.4 fb(-1) of data collected with the D0 detector during 2002-2004. Using 5176 reconstructed Ds- mu+ signal events, we have measured the Bs(0) lifetime to be tau(Bs(0))=1.398+/-0.044(stat)(-0.025)(+0.028)(syst) ps. This is the most precise measurement of the Bs(0) lifetime to date. PMID- 17280288 TI - Radiation pressure cooling of a micromechanical oscillator using dynamical backaction. AB - Cooling of a 58 MHz micromechanical resonator from room temperature to 11 K is demonstrated using cavity enhanced radiation pressure. Detuned pumping of an optical resonance allows enhancement of the blueshifted motional sideband (caused by the oscillator's Brownian motion) with respect to the redshifted sideband leading to cooling of the mechanical oscillator mode. The reported cooling mechanism is a manifestation of the effect of radiation pressure induced dynamical backaction. These results constitute an important step towards achieving ground state cooling of a mechanical oscillator. PMID- 17280289 TI - Exploring the phase space of the quantum delta-kicked accelerator. AB - We experimentally explore the underlying pseudoclassical phase space structure of the quantum delta-kicked accelerator. This was achieved by exposing a Bose Einstein condensate to the spatially corrugated potential created by pulses of an off-resonant standing light wave. For the first time quantum accelerator modes were realized in such a system. By utilizing the narrow momentum distribution of the condensate we were able to observe the discrete momentum state structure of a quantum accelerator mode and also to directly measure the size of the structures in the phase space. PMID- 17280290 TI - Impact dynamics for elastic membranes. AB - We study the dynamic response of stretched thin polymeric films following an impact by a rigid sphere. We vary the sphere radius, the impact velocity, and the film tension, and measure the contact time and the maximum deflection of the film during the impact. The response is sensitive to nonlinearities associated with the additional tension provided by the deformation. A physical model at the scaling level is presented. This allows us (i) to understand qualitatively experimental and numerical results and (ii) to present a diagram mapping different possible impact dynamics for membrane systems, which accounts for the interplay between membrane tension, intrinsic modulus, and geometrical factors such as the frame size and the sphere radius. PMID- 17280292 TI - Drop formation by thermal fluctuations at an ultralow surface tension. AB - We present experimental evidence that drop breakup is caused by thermal noise in a system with a surface tension that is more than 10(6) times smaller than that of water. We observe that at very small scales classical hydrodynamics breaks down and the characteristic signatures of pinch-off due to thermal noise are observed. Surprisingly, the noise makes the drop size distribution more uniform, by suppressing the formation of satellite droplets of the smallest sizes. The crossover between deterministic hydrodynamic motion and stochastic thermally driven motion has repercussions for our understanding of small-scale hydrodynamics, important in many problems such as micro- or nanofluidics and interfacial singularities. PMID- 17280291 TI - How waves affect the distribution of particles that float on a liquid surface. AB - We study experimentally how waves affect the distribution of particles that float on a liquid surface. We show that clustering of small particles in a standing wave is a nonlinear effect with the clustering time decreasing as the square of the wave amplitude. In a set of random waves, we show that small floaters concentrate on a multifractal set with caustics. PMID- 17280293 TI - Small-scale structures in three-dimensional magnetohydrodynamic turbulence. AB - We investigate using direct numerical simulations with grids up to 1536(3) points, the rate at which small scales develop in a decaying three-dimensional MHD flow both for deterministic and random initial conditions. Parallel current and vorticity sheets form at the same spatial locations, and further destabilize and fold or roll up after an initial exponential phase. At high Reynolds numbers, a self-similar evolution of the current and vorticity maxima is found, in which they grow as a cubic power of time; the flow then reaches a finite dissipation rate independent of the Reynolds number. PMID- 17280271 TI - Observation of Bs(0)-Bs(0) oscillations. AB - We report the observation of Bs(0)-Bs(0) oscillations from a time-dependent measurement of the Bs(0)-Bs(0) oscillation frequency Deltams. Using a data sample of 1 fb(-1) of pp collisions at square root of s=1.96 TeV collected with the CDF II detector at the Fermilab Tevatron, we find signals of 5600 fully reconstructed hadronic Bs decays, 3100 partially reconstructed hadronic Bs decays, and 61,500 partially reconstructed semileptonic Bs decays. We measure the probability as a function of proper decay time that the Bs decays with the same, or opposite, flavor as the flavor at production, and we find a signal for Bs(0)-Bs(0) oscillations. The probability that random fluctuations could produce a comparable signal is 8 x 10(-8), which exceeds 5sigma significance. We measure Deltams=17.77 +/- 0.10(stat) +/- 0.07(syst) ps(-1) and extract /V(td)/V(ts)/=0.2060+/ 0.0007(Deltams)(-0.0060)(+0.008)(Deltamd+theor). PMID- 17280294 TI - Small-scale turbulence in a closed-field-line geometry. AB - Plasma turbulence due to small-scale entropy modes is studied with gyrokinetic simulations in a simple closed-field-line geometry, the Z pinch, in low-beta parameter regimes that are stable to ideal interchange modes. We find an enormous variation in the nonlinear dynamics and particle transport as a function of two main parameters, the density gradient and the plasma collisionality. This variation is explained in part by the damping and stability properties of spontaneously formed zonal flows in the system. As in toroidal systems, the zonal flows can lead to a strong nonlinear suppression of transport below a critical gradient that is determined by the stability of the zonal flows. PMID- 17280296 TI - Transient deformation regime in bending of single-walled carbon nanotubes. AB - Pure bending of single-walled carbon nanotubes between (5,5) and (50,50) is studied using molecular dynamics based on the reactive bond order potential. Unlike smaller nanotubes, bending of (15,15) and larger ones exhibits an intermediate deformation in the transition between the buckled and fully kinked configurations. This transient bending regime is characterized by a gradual and controllable flattening of the nanotube cross section at the buckling site. Unbending of a kinked nanotube bypasses the transient bending regime, exhibiting a hysteresis due to van der Waals attraction between the tube walls at the kinked site. PMID- 17280297 TI - Weissenberg reflection high-energy electron diffraction for surface crystallography. AB - The principle of a Weissenberg camera is applied to surface crystallographic analysis by reflection high-energy electron diffraction. By removing inelastic electrons and measuring hundreds of patterns as a function of sample rotation angle phi, kinematical analysis can be performed over a large volume of reciprocal space. The data set is equivalent to a three-dimensional stack of Weissenberg photographs. The method is applied to analysis of an Si(111)-square root of 3 x square root of 3-Ag surface, and the structural data obtained are in excellent agreement with the known atomic structure. PMID- 17280295 TI - Search for superfluidity in solid hydrogen. AB - A torsional oscillator study of solid para-hydrogen has been carried out down to 20 mK in a search for evidence of superfluidity. We found evidence of a possible phase transition, marked by an abrupt increase in the resonant period of oscillation and onset of extremely long relaxation times as the temperature was raised above 60 mK. In contrast to solid 4He, the change in the period for para hydrogen is not a consequence of irrotational superflow. The long relaxation times observed suggest the effect is related to the motion of residual ortho hydrogen molecules in the solid. PMID- 17280298 TI - Charge redistribution and phonon entropy of vanadium alloys. AB - The effects of alloying on the lattice dynamics of vanadium were investigated using inelastic neutron scattering. Phonon densities of states were obtained for bcc solid solutions of V with 3d, 4d, and 5d transition metal solutes, from which vibrational entropies of alloying were obtained. A good correlation is found between the vibrational entropy of alloying and the electronegativity of transition metal solutes across the 3d row and down columns of the periodic table. First-principles calculations on supercells matching the experimental compositions predicted a systematic charge redistribution in the nearest-neighbor shell around the solute atoms, also following the Pauling and Watson electronegativity scales. The systematic stiffening of the phonons is interpreted in terms of the modified screening properties of the electron density around the solutes. PMID- 17280299 TI - Liquidlike behavior of supercritical fluids. AB - The high frequency dynamics of fluid oxygen has been investigated by inelastic x ray scattering, at high pressures and room temperature. In spite of the markedly supercritical conditions (T approximately 2Tc, P>10(2)Pc), the sound velocity exceeds the hydrodynamic value of about 20%, a feature which is the fingerprint of liquidlike dynamics. The comparison of the present results with literature data obtained in several fluids allow us to identify the extrapolation of the liquid-vapor-coexistence line in the (P/Pc, T/Tc) plane as the relevant edge between liquidlike and gaslike dynamics. More interestingly, this extrapolation is very close to the non-metal-metal transition in hot dense fluids, at pressure and temperature values as obtained by shock wave experiments. This result points to the existence of a connection between structural modifications and transport properties in dense fluids. PMID- 17280301 TI - Do deviations from reptation scaling of entangled polymer melts result from single- or many-chain effects? AB - By studying the relaxation of small amounts of short entangled "probe" chains in a high molecular weight matrix, we show that the deviations from reptation scaling of the longest relaxation time are not as much dominated by single-chain effects (usually referred to as contour length fluctuations or CLF) as assumed by current mesoscopic models but also originate to a very significant extent from mutual chain relaxation effects. This result is in fact consistent with literature data on tracer and self-diffusion. Moreover, tube theories also overpredict the influence of CLF on the plateau modulus. Improved theories, simulations, and careful experiments are urgently needed to resolve this important question. PMID- 17280300 TI - Kinetics and mechanism of proton transport across membrane nanopores. AB - We use computer simulations to study the kinetics and mechanism of proton passage through a narrow-pore carbon-nanotube membrane separating reservoirs of liquid water. Free energy and rate constant calculations show that protons move across the membrane diffusively along single-file chains of hydrogen-bonded water molecules. Proton passage through the membrane is opposed by a high barrier in the effective potential, reflecting the large electrostatic penalty for desolvation and reminiscent of charge exclusion in biological water channels. At neutral pH, we estimate a translocation rate of about 1 proton per hour and tube. PMID- 17280302 TI - Electron core-hole interaction and its induced ionic structural relaxation in molecular systems under x-ray irradiation. AB - The experiments on perylene-3,4,9,10-tetracarboxylic-3,4,9,10-dianhydride and 16FCuPc on Ag(111) surfaces by the normal incidence x-ray standing wave are poorly reproduced by first-principles ground state calculations but well reproduced by considering initial- and final-state effects, which include the response of the valence electrons to screen a core hole created by x-ray photoemission and further induced ionic structural relaxation. This study shows that the initial- and final-state effects due to screening are of great importance in characterizing molecules on metal surfaces in the normal incidence x-ray standing wave experiments. PMID- 17280303 TI - Interfaces between Al2O3 and beta-Ni(1-x)Al(x) alloys: complex structures and Ab initio thermodynamics. AB - A methodology to study the structural stability of binary alloy/Al2O3 interfaces is developed by expanding the conventional ab initio thermodynamics to include the dependence on alloy composition. Results on beta-Ni(1-x)Al(x)/Al2O3 interfaces predict the existence of two types of stable interfaces. The stable interface at equilibrium with Al-rich or strictly 1:1 alloy contains an Al2 terminated Al2O3 surface and continues with NiAl layers, and the interface at equilibrium with Ni-rich alloy has Al accumulation but continues with a Ni-rich and then NiAl layers. Works of separation for the two interfaces are close to each other. PMID- 17280304 TI - Nonlinear quantum shock waves in fractional quantum Hall edge states. AB - Using the Calogero model as an example, we show that the transport in interacting nondissipative electronic systems is essentially nonlinear and unstable. Nonlinear effects are due to the curvature of the electronic spectrum near the Fermi energy. As is typical for nonlinear systems, a propagating semiclassical wave packet develops a shock wave at a finite time. A wave packet collapses into oscillatory features which further evolve into regularly structured localized pulses carrying a fractionally quantized charge. The Calogero model can be used to describe fractional quantum Hall edge states. We discuss perspectives of observation of quantum shock waves and a direct measurement of the fractional charge in fractional quantum Hall edge states. PMID- 17280305 TI - Orthogonality catastrophe and shock waves in a nonequilibrium Fermi gas. AB - A semiclassical wave packet propagating in a dissipationless Fermi gas inevitably enters a "gradient catastrophe" regime, where an initially smooth front develops large gradients and undergoes a dramatic shock-wave phenomenon. The nonlinear effects in electronic transport are due to the curvature of the electronic spectrum at the Fermi surface. They can be probed by a sudden switching of a local potential. In equilibrium, this process produces a large number of particle hole pairs, a phenomenon closely related to the orthogonality catastrophe. We study a generalization of this phenomenon to the nonequilibrium regime and show how the orthogonality catastrophe cures the gradient catastrophe, by providing a dispersive regularization mechanism. PMID- 17280306 TI - Low-magnetic-field divergence of the electronic g factor obtained from the cyclotron spin-flip mode of the nu=1 quantum Hall ferromagnet. AB - We report an inelastic light scattering study of the cyclotron spin-flip mode in the two-dimensional electron system at filling nu=1. The energy of this mode can serve as a probe of the many-body exchange interaction on short length scales. Its magnetic field dependence is compared with predictions based on Hartree-Fock theory. They agree well when including the nonzero width of the electron system. From the measured energies, the exchange enhanced g factor is extracted. It diverges at small fields and differs largely from g factors obtained via transport activation studies. PMID- 17280307 TI - Spectroscopic measurement of spin-dependent resonant tunneling through a 3D disorder: the case of MnAs/GaAs/MnAs junctions. AB - We propose an analytical model of spin-dependent resonant tunneling through a 3D assembly of localized states (spread out in energy and in space) in a barrier. An inhomogeneous distribution of localized states leads to resonant tunneling magnetoresistance inversion and asymmetric bias dependence as evidenced with a set of experiments with MnAs/GaAs(7-10 nm)/MnAs tunnel junctions. One of the key parameters of our theory is a dimensionless critical exponent beta scaling the typical extension of the localized states over the characteristic length scale of the spatial distribution function. Furthermore, we demonstrate, through experiments with localized states introduced preferentially in the middle of the barrier, the influence of an homogeneous distribution on the spin-dependent transport properties. PMID- 17280308 TI - Generation of spin current by Coulomb drag. AB - Coulomb drag between two quantum wires is exponentially sensitive to the mismatch of their electronic densities. The application of a magnetic field can compensate this mismatch for electrons of opposite spin directions in different wires. The resulting enhanced momentum transfer leads to the conversion of the charge current in the active wire to the spin current in the passive wire. PMID- 17280309 TI - 0-pi Josephson tunnel junctions with ferromagnetic barrier. AB - We fabricated high quality Nb/Al2O3/Ni(0.6)Cu(0.4)/Nb superconductor-insulator ferromagnet-superconductor Josephson tunnel junctions. Using a ferromagnetic layer with a steplike thickness, we obtain a 0-pi junction, with equal lengths and critical currents of 0 and pi parts. The ground state of our 330 microm (1.3lambda(J)) long junction corresponds to a spontaneous vortex of supercurrent pinned at the 0-pi step and carrying approximately 6.7% of the magnetic flux quantum Phi(0). The dependence of the critical current on the applied magnetic field shows a clear minimum in the vicinity of zero field. PMID- 17280310 TI - From E2g to other modes: effects of pressure on electron-phonon interaction in MgB2. AB - We study the effects of pressure on the electron-phonon interaction in MgB2 using density-functional-based methods. Our results show that the superconductivity in MgB2 vanishes by 100 GPa, and then reappears at higher pressures. In particular, we find a superconducting transition temperature Tc approximately 2 K for mu*=0.1 at a pressure of 137 GPa. PMID- 17280311 TI - Interplay of externally doped and thermally activated holes in La(2-x)Sr(x)CuO4 and their impact on the pseudogap crossover. AB - We presented the recent Hall effect data for a number of carriers in La(2 x)Sr(x)CuO4 as the sum of two components: the temperature independent term n0(x), which is due to external doping, and the thermally activated contribution. Their balance determines the crossover temperature T*(x) from the marginal Fermi liquid to pseudogap regime. The activation energy Delta(x) for thermally excited carriers equals the energy between the Fermi surface "arc" and the band bottom, as seen in angle-resolved photoemission spectroscopy experiments. Other implications for the (T, x)-phase diagram of cuprates are also discussed. PMID- 17280312 TI - First-order phase transition in easy-plane quantum antiferromagnets. AB - Quantum phase transitions in Mott insulators do not fit easily into the Landau Ginzburg-Wilson paradigm. A recently proposed alternative to it is the so-called deconfined quantum criticality scenario, providing a new paradigm for quantum phase transitions. In this context it has recently been proposed that a second order phase transition would occur in a two-dimensional spin 1/2 quantum antiferromagnet in the deep easy-plane limit. A check of this conjecture is important for understanding the phase structure of Mott insulators. To this end we have performed large-scale Monte Carlo simulations on an effective gauge theory for this system, including a Berry-phase term that projects out the S=1/2 sector. The result is a first-order phase transition, thus contradicting the conjecture. PMID- 17280313 TI - Photoinduced magnetism caused by charge-transfer excitations in tetracyanoethylene-based organic magnets. AB - The photoinduced magnetism in Mn-tetracyanoethylene (TCNE) molecule-based magnets is ascribed to charge-transfer excitations from manganese to TCNE. Charge transfer energies are calculated using density functional theory; photoinduced magnetization is described using a model Hamiltonian based on a double-exchange mechanism. Photoexciting electrons from the manganese core spins into the lowest unoccupied orbital of TCNE with photon energies around 3 eV increase the magnetization through a reduction of the canting angle of the manganese core spins for an average electron density on TCNE less than one. When photoexciting with a smaller energy, divalent TCNE molecules are formed. The delocalization of the excited electron causes a local spin flip of a manganese core spin. PMID- 17280314 TI - Splitting of spin excitations in nanometric rings induced by a magnetic field. AB - We present a Brillouin light scattering investigation of the eigenmode spectrum of nanometric permalloy rings as a function of the applied magnetic field. In particular, different splitting effects induced by the applied magnetic field on the radial and azimuthal excitations have been observed and explained in terms of either mode localization or symmetry. The dynamical matrix approach has been used to calculate the whole set of eigenvectors and eigenvalues of the system, in both the vortex and saturated states. PMID- 17280315 TI - Coexisting ferromagnetic order and disorder in a uniform system of hydroxyhalide Co2(OH)3Cl. AB - Order or disorder often exists in a uniform spin system consisting of one kind of magnetic ion. Nevertheless, they rarely coexist in normal conditions. Our thermodynamic and microscopic magnetic studies of Co2(OH)3Cl, a distorted tetrahedral lattice compound with uniform Co2+ spin, demonstrate that the spins located on one corner of the tetrahedron are periodically ordered, but those on the other three are disordered below a ferromagnetic transition at TC=10.5 K. The partial order resembles that of the field-induced "kagome-ice" state in spin ice pyrochlore compounds. Evidence suggests that a distortion in the tetrahedron is responsible for this partial ferromagnetic order in a zero field. PMID- 17280316 TI - Multiple photonic responses in films of organic-based magnetic semiconductor V(TCNE)x, x approximately 2. AB - Concomitant photoinduced magnetic and electrical phenomena are reported for the organic-based magnetic semiconductor V(TCNE)x (x approximately 2; TCNE=tetracyanoethylene; magnetic ordering temperature Tc approximately 400 K). Upon optical excitation (457.9 nm), the system can be trapped in a thermally reversible photoexcited state, which exhibits reduced magnetic susceptibility and increased conductivity with a simultaneous change in IR absorption spectrum. The multiple photonic effects in V(TCNE)x are proposed to originate from structural changes induced by internal excitation in (TCNE)- anions, which lead to relaxation to a long-lived metastable state. PMID- 17280317 TI - In-gap spin excitations and finite triplet lifetimes in the dilute singlet ground state system SrCu(2-x)Mgx(BO3)2. AB - High resolution neutron scattering measurements on a single crystal of SrCu(2 x)Mgx(BO3)2 with x approximately 0.05 reveal the presence of new spin excitations within the gap of this quasi-two-dimensional, singlet ground state system. The application of a magnetic field induces Zeeman-split states associated with S=1/2 unpaired spins which are antiferromagnetically correlated with the bulk singlet. Substantial broadening of both the one- and two-triplet excitations in the doped single crystal is observed, as compared with pure SrCu2(BO3)2. Theoretical calculations using a variational algorithm and a single quenched magnetic vacancy on an infinite lattice are shown to qualitatively account for these effects. PMID- 17280318 TI - Electronic spin precession and interferometry from spin-orbital entanglement in a double quantum dot. AB - A double quantum dot inserted in parallel between two metallic leads can entangle the electron spin with the orbital (dot index) degree of freedom. An Aharonov Bohm orbital phase can be transferred to the spinor wave function, providing a geometrical control of the spin precession around a fixed magnetic field. A fully coherent behavior occurs in a mixed orbital-spin Kondo regime. Evidence for the spin precession can be obtained, either using spin-polarized metallic leads or by placing the double dot in one branch of a metallic loop. PMID- 17280319 TI - Spin-state transition in LaCoO3: direct neutron spectroscopic evidence of excited magnetic states. AB - A gradual spin-state transition occurs in LaCoO3 around T approximately 80-120 K, whose detailed nature remains controversial. We studied this transition by means of inelastic neutron scattering and found that with increasing temperature an excitation at approximately 0.6 meV appears, whose intensity increases with temperature, following the bulk magnetization. Within a model including crystal field interaction and spin-orbit coupling, we interpret this excitation as originating from a transition between thermally excited states located about 120 K above the ground state. We further discuss the nature of the magnetic excited state in terms of intermediate-spin (t(2g)(5)e(g)(1), S=1) versus high-spin (t(2g)(4)e(g)(2), S=2) states. Since the g factor obtained from the field dependence of the inelastic neutron scattering is g approximately 3, the second interpretation is definitely favored. PMID- 17280320 TI - Vortex chirality in exchange-biased elliptical magnetic rings. AB - The flux-closed or "vortex" state in thin-film magnetic rings has been proposed as a data storage token, but it has proven difficult to control the vortex chirality in a simple manner. Here, a model is described that predicts the vortex chirality of an elliptical magnetic ring as a function of the direction of the applied field and of the exchange bias, based on the change in energy of the system as the domain walls move. Experimental measurements of chirality in Co and Co/IrMn magnetic rings with 3.2 microm major axis are in excellent agreement with the model. The vortex circulation direction can therefore be tailored with an appropriate combination of applied field direction and exchange bias direction with respect to the major axis. PMID- 17280321 TI - Coherent population trapping of single spins in diamond under optical excitation. AB - Coherent population trapping is demonstrated in single nitrogen-vacancy centers in diamond under optical excitation. For sufficient excitation power, the fluorescence intensity drops almost to the background level when the laser modulation frequency matches the 2.88 GHz splitting of the ground states. The results are well described theoretically by a four-level model, allowing the relative transition strengths to be determined for individual centers. The results show that all-optical control of single spins is possible in diamond. PMID- 17280322 TI - Ultrafast electron pulses from a tungsten tip triggered by low-power femtosecond laser pulses. AB - We present an experimental and numerical study of electron emission from a sharp tungsten tip triggered by sub-8-fs low-power laser pulses. This process is nonlinear in the laser electric field, and the nonlinearity can be tuned via the dc voltage applied to the tip. Numerical simulations of this system show that electron emission takes place within less than one optical period of the exciting laser pulse, so that an 8 fs 800 nm laser pulse is capable of producing a single electron pulse of less than 1 fs duration. Furthermore, we find that the carrier envelope phase dependence of the emission process is smaller than 0.1% for an 8 fs pulse but is steeply increasing with decreasing laser pulse duration. PMID- 17280323 TI - Nonvolatile gate effect in a ferroelectric-semiconductor quantum well. AB - Field effect transistors with ferroelectric gates would make ideal rewritable nonvolatile memories were it not for the severe problems in integrating the ferroelectric oxide directly on the semiconductor channel. We propose a powerful way to avoid these problems using a gate material that is ferroelectric and semiconducting simultaneously. First, ferroelectricity in semiconductor (Cd,Zn)Te films is proven and studied using modified piezoforce scanning probe microscopy. Then, a rewritable field effect device is demonstrated by local poling of the (Cd,Zn)Te layer of a (Cd,Zn)Te/CdTe quantum well, provoking a reversible, nonvolatile change in the resistance of the 2D electron gas. The results point to a potential new family of nanoscale one-transistor memories. PMID- 17280324 TI - Polarization switching dynamics governed by the thermodynamic nucleation process in ultrathin ferroelectric films. AB - In most ferroelectrics, the domain nucleation barrier (U*) is thermally insurmountable; this is called "Landauer's paradox." However, we showed that, in ultrathin films, the large depolarization fields could lower U* to a level comparable to thermal energy (k(B)T), resulting in power-law decay of polarization. We empirically found a universal relation between the power-law decay exponent and U*/k(B)T. This relation will provide a practical but fundamental limit for capacitor-type ferroelectric devices, analogous to the superparamagnetic limit for magnetic memory devices. PMID- 17280325 TI - Production of photocurrent due to intermediate-to-conduction-band transitions: a demonstration of a key operating principle of the intermediate-band solar cell. AB - We present intermediate-band solar cells manufactured using quantum dot technology that show for the first time the production of photocurrent when two sub-band-gap energy photons are absorbed simultaneously. One photon produces an optical transition from the intermediate-band to the conduction band while the second pumps an electron from the valence band to the intermediate-band. The detection of this two-photon absorption process is essential to verify the principles of operation of the intermediate-band solar cell. The phenomenon is the cornerstone physical principle that ultimately allows the production of photocurrent in a solar cell by below band gap photon absorption, without degradation of its output voltage. PMID- 17280326 TI - Anomalous behavior of proton zero point motion in water confined in carbon nanotubes. AB - The momentum distribution of the protons in ice Ih, ice VI, high density amorphous ice, and water in carbon nanotubes has been measured using deep inelastic neutron scattering. We find that at 5 K the kinetic energy of the protons is 35 meV less than that in ice Ih at the same temperature, and the high momentum tail of the distribution, characteristic of the molecular covalent bond, is not present. We observe a phase transition between 230 and 268 K to a phase that does resemble ice Ih. Although there is yet no model for water that explains the low temperature momentum distribution, our data reveal that the protons in the hydrogen bonds are coherently delocalized and that the low temperature phase is a qualitatively new phase of ice. PMID- 17280327 TI - Confinement effects in polymer crystal nucleation from the bulk to few-chain systems. AB - We have studied crystallization in poly(ethylene oxide) droplets with volumes ranging over several orders of magnitude. In all samples, homogeneous nucleation is observed, scaling with the volume of the droplet, down to systems with as few as approximately 10 polymer chains. Surprisingly, nucleation is unaffected by the high degree of confinement, despite a large surface-to-volume ratio and the restriction of chains to length scales much smaller than the radius of gyration. Nucleation was also found to be independent of chain length for two molecular weights studied, differing by an order of magnitude. The results suggest that, for these highly supercooled systems, the formation of a nucleus is influenced by its immediate surroundings and does not depend on the entire length of the constituent chains. PMID- 17280328 TI - Elasticity of alpha-helical coiled coils. AB - Predicting large scale conformations of protein structures is computationally demanding. Here we compute the conformation and elasticity of double-stranded coiled coils using a simple coarse-grained elastic model. By maximizing the contact between hydrophobic residues and minimizing the elastic energy, we show that the minimum energy structure of a coiled coil is a supercoiled double helix of alpha helices. For realistic binding energies, the elastic energy of the alpha helices requires binding every 7th residue, which leads to a pitch and helix angle for the structure that is consistent with experimental measurements. Analysis of the model equations shows how the pitch varies with the helical repeat of the hydrophobic residues and with the ratio of the twisting modulus to the bending modulus and provides an estimate of the persistence length of around 150 nm, in agreement with previous experimental estimates. PMID- 17280329 TI - Direct observation of hydrodynamic rotation-translation coupling between two colloidal spheres. AB - By combining optical tweezers with polarization microscopy, the hydrodynamic coupling between position and orientation fluctuations in a pair of colloidal spheres has been measured. Imaging of birefringent particles under crossed polarizers allows for the simultaneous determination of the positions and orientations of both particles. The temporal cross-correlation function between random displacements of one particle and orientation fluctuations of its neighbor allows for the quantification of the hydrodynamic rotation-translation coupling between the spheres. Our results are in good agreement with predictions for the hydrodynamic mobility tensors calculated in the creeping-flow limit of the Navier Stokes equation. PMID- 17280330 TI - Superfluid transition in a rotating fermi gas with resonant interactions. AB - We study a rotating atomic Fermi gas near a narrow s-wave Feshbach resonance in a uniaxial trap with frequencies Omega perpendicular, Omega z. We predict the upper critical angular velocity, omega c2(delta,T), as a function of temperature T and detuning delta across the BEC-BCS crossover. The suppression of superfluidity at omega c2 is distinct in the BCS and BEC regimes, with the former controlled by depairing and the latter by the dilution of bosonic molecules. At low T and Omega z << Omega perpendicular, in the BCS and crossover regimes of 0 less similar delta less similar delta c, omega c2 is implicitly given by [formula: see text], vanishing as omega c2 approximately Omega perpendicular(1 - delta/delta c)(1/2) near [formula: see text] (with Delta the BCS gap and gamma the resonance width), and extending the bulk result variant Planck's over 2pi omega c2 approximately 2Delta2/epsilonF to a trap. In the BEC regime of delta < 0 we find omega c2- >Omega perpendicular-, where molecular superfluidity is destroyed only by large quantum fluctuations associated with comparable boson and vortex densities. PMID- 17280331 TI - Comparing contact and dipolar interactions in a Bose-Einstein condensate. AB - We have measured the relative strength epsilon dd of the magnetic dipole-dipole interaction compared with the contact interaction in a dipolar chromium Bose Einstein condensate. We analyze the asymptotic velocities of expansion of the condensate with different orientations of the atomic magnetic moments. By comparing the experimental results with numerical solutions of the hydrodynamic equations for dipolar condensates, we obtain epsilon dd = 0.159+/-0.034. We use this result to determine the s-wave scattering length a = (5.08+/-1.06 x 10(-9)) m = (96+/-20) a0 of 52Cr. This is fully consistent with our previous measurements on the basis of Feshbach resonances and therefore confirms the validity of the theoretical approach used to describe the dipolar Bose-Einstein condensate. PMID- 17280332 TI - Experimental evidence for the breakdown of a Hartree-Fock approach in a weakly interacting Bose gas. AB - We investigate the physics underlying the presence of a quasicondensate in a nearly one dimensional, weakly interacting trapped atomic Bose gas. We show that a Hartree-Fock (mean-field) approach fails to predict the existence of the quasicondensate in the center of the cloud: the quasicondensate is generated by interaction-induced correlations between atoms and not by a saturation of the excited states. Numerical calculations based on Bogoliubov theory give an estimate of the crossover density in agreement with experimental results. PMID- 17280333 TI - Quest for quantum superpositions of a mirror: High and moderately low temperatures. AB - The Born-Markov master equation analysis of the vibrating mirror and photon experiment proposed by Marshall, Simon, Penrose, and Bouwmeester is completed by including the important issues of temperature and friction. We find that at the level of cooling available to date, visibility revivals are purely classical, and no quantum effect can be detected by the setup, no matter how strong the photon mirror coupling is. Checking proposals of universal nonenvironmental decoherence is ruled out by dominating thermal decoherence; a conjectured coordinate diffusion contribution to decoherence may become observable on reaching moderately low temperatures. PMID- 17280334 TI - Security of quantum bit string commitment depends on the information measure. AB - Unconditionally secure nonrelativistic bit commitment is known to be impossible in both the classical and the quantum world. However, when committing to a string of n bits at once, how far can we stretch the quantum limits? In this Letter, we introduce a framework of quantum schemes where Alice commits a string of n bits to Bob, in such a way that she can only cheat on a bits and Bob can learn at most b bits of information before the reveal phase. Our results are twofold: we show by an explicit construction that in the traditional approach, where the reveal and guess probabilities form the security criteria, no good schemes can exist: a + b is at least n. If, however, we use a more liberal criterion of security, the accessible information, we construct schemes where a = 4log2(n) + O(1) and b = 4, which is impossible classically. Our findings significantly extend known no-go results for quantum bit commitment. PMID- 17280335 TI - Relativity and lorentz invariance of entanglement distillability. AB - We study entanglement distillability of bipartite mixed spin states under Wigner rotations induced by Lorentz transformations. We define weak and strong criteria for relativistic isoentangled and isodistillable states to characterize relative and invariant behavior of entanglement and distillability. We exemplify these criteria in the context of Werner states, where fully analytical methods can be achieved and all relevant cases presented. PMID- 17280336 TI - Quantum information becomes classical when distributed to many users. AB - Any physical transformation that equally distributes quantum information over a large number M of users can be approximated by a classical broadcasting of measurement outcomes. The accuracy of the approximation is at least of the order O(M(-1)). In particular, quantum cloning of pure and mixed states can be approximated via quantum state estimation. As an example, for optimal qubit cloning with 10 output copies, a single user has an error probability p(err) > or = 0.45 in distinguishing classical from quantum output, a value close to the error probability of the random guess. PMID- 17280337 TI - All-optical measurement-based quantum-information processing in quantum dots. AB - Parity measurements on qubits can generate the entanglement resource necessary for scalable quantum computation. Here we describe a method for fast optical parity measurements on electron spin qubits within coupled quantum dots. The measurement scheme, which can be realized with existing technology, consists of the optical excitation of excitonic states followed by monitored relaxation. Conditional on the observation of a photon, the system is projected into the odd/even-parity subspaces. Our model incorporates all the primary sources of error, including detector inefficiency, effects of spatial separation and nonresonance of the dots, and also unwanted excitations. Through an analytical treatment we establish that the scheme is robust to such effects. Two applications are presented: a realization of a controlled-NOT gate, and a technique for growing large scale graph states. PMID- 17280338 TI - Effective coupling between two Brownian particles. AB - We use the system-plus-reservoir approach to study the dynamics of a system composed of two independent Brownian particles. We present an extension of the well-known model of a bath of oscillators which is capable of inducing an effective coupling between the two particles depending on the choice made for the spectral function of the bath oscillators. The coupling is nonlinear in the variables of interest, and an exponential dependence on these variables is imposed in order to guarantee the translational invariance of the model if the two particles are not subject to any external potential. The effective equations of motion for the particles are obtained by the Laplace transform method, and, besides recovering all the local dynamical properties for each particle, we end up with an effective interaction potential between them. We explicitly analyze one of its possible forms. PMID- 17280339 TI - Enhanced polarization of the cosmic microwave background radiation from thermal gravitational waves. AB - If inflation was preceded by a radiation era, then at the time of inflation there will exist a decoupled thermal distribution of gravitons. Gravitational waves generated during inflation will be amplified by the process of stimulated emission into the existing thermal distribution of gravitons. Consequently, the usual zero temperature scale invariant tensor spectrum is modified by a temperature dependent factor. This thermal correction factor amplifies the B-mode polarization of the cosmic microwave background radiation by an order of magnitude at large angles, which may now be in the range of observability of the Wilkinson Microwave Anisotropy Probe. PMID- 17280340 TI - Absolute branching fraction measurements for D+ and D0 inclusive semileptonic decays. AB - We present measurements of the inclusive branching fractions for the decays D+- >Xe+ nu(e) and D0-->Xe+ nu(e), using 281 pb(-1) of data collected on the psi(3770) resonance with the CLEO-c detector. We find B(D0-->Xe+ nu(e)) = (6.46+/ 0.17+/-0.13)% and B(D+-->Xe+ nu(e)) = (16.13+/-0.20+/-0.33)%. Using the known D meson lifetimes, we obtain the ratio Gamma(D+)sl/Gamma(D0)sl = 0.985+/-0.028+/ 0.015, confirming isospin invariance at the level of 3%. The positron momentum spectra from D+ and D0 have consistent shapes. PMID- 17280344 TI - Small-x behavior of parton distributions from the observed Froissart energy dependence of the deep-inelastic-scattering cross sections. AB - We fit the reduced cross section for deep-inelastic electron scattering data to a three parameter ln2s fit, A + beta ln2(s/s0), where s = (Q2/x)(1-x) + m2, and Q2 is the virtuality of the exchanged photon. Over a wide range in Q2 (0.11 < or = Q2 < or = 1200 GeV2) all of the fits satisfy the logarithmic energy dependence of the Froissart bound. We can use these results to extrapolate to very large energies and hence to very small values of Bjorken x-well beyond the range accessible experimentally. As Q2-->infinity, the structure function F2(p)(x,Q2) exhibits Bjorken scaling, within experimental errors. We obtain new constraints on the behavior of quark and antiquark distribution functions at small x. PMID- 17280345 TI - Plasma instabilities in an anisotropically expanding geometry. AB - We study (3+1)D kinetic (Boltzmann-Vlasov) equations for relativistic plasma particles in a one dimensionally expanding geometry motivated by ultrarelativistic heavy-ion collisions. We set up local equations in terms of Yang-Mills potentials and auxiliary fields that allow simulations of hard- (expanding-) loop dynamics on a lattice. We determine numerically the evolution of plasma instabilities in the linear (Abelian) regime and also derive their late time behavior analytically, which is consistent with recent numerical results on the evolution of the so-called melting color-glass condensate. We also find a significant delay in the onset of growth of plasma instabilities which are triggered by small rapidity fluctuations, even when the initial state is highly anisotropic. PMID- 17280341 TI - Evidence of the purely leptonic decay B- --> tau- nu(tau). AB - We present the first evidence of the decay B- --> tau- nu(tau), using 414 fb(-1) of data collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+ e- collider. Events are tagged by fully reconstructing one of the B mesons in hadronic modes. We detect the signal with a significance of 3.5 standard deviations including systematics and measure the branching fraction to be B(B- --> tau- nu(tau)) = (1.79(-0.49) +0.56(stat)(-0.51) +0.46(syst)) x 10(-4). This implies that fB = 0.229(-0.031) +0.036(stat)(-0.037) +0.034(syst) GeV and is the first direct measurement of this quantity. PMID- 17280346 TI - Memory in nonlinear ionization of transparent solids. AB - We demonstrate a shot-to-shot reduction in the threshold laser intensity for ionization of bulk glasses illuminated by intense femtosecond pulses. For SiO2 the threshold change serves as positive feedback reenforcing the process that produced it. This constitutes a memory in nonlinear ionization of the material. The threshold change saturates with the number of pulses incident at a given spot. Irrespective of the pulse energy, the magnitude of the saturated threshold change is constant (approximately 20%). However, the number of shots required to reach saturation does depend on the pulse energy. Recognition of a memory in ionization is vital to understand multishot optical or electrical breakdown phenomena in dielectrics. PMID- 17280347 TI - Magnetic-field induced enhancement in the fluorescence yield spectrum of doubly excited states in helium. AB - An influence of static magnetic fields on the fluorescence yield spectrum of He in the vicinity of the N = 2 thresholds has been observed. The experimental results are in excellent agreement with predictions based on multichannel quantum defect theory, and it is demonstrated that the Rydberg electron l mixing due to the diamagnetic interaction is essential for the description of the observed fluorescence yield intensity enhancement. PMID- 17280348 TI - Navigating localized wave packets in phase space. AB - The ability to localize and to steer Rydberg wave packets in phase space using tailored sequences of half-cycle pulses is demonstrated. Classical phase-space portraits are used to explain the method and to illustrate the level of control that can be achieved. This is confirmed experimentally by positioning a phase space-localized wave packet at the center of a stable island or navigating it around its periphery. This work provides a valuable starting point for further engineering of electronic wave functions. PMID- 17280349 TI - Nonperturbative calculation of the two-loop lamb shift in Li-like ions. AB - A calculation valid to all orders in the nuclear-strength parameter is presented for the two-loop Lamb shift, notably for the two-loop self-energy correction, to the 2p-2s transition energies in heavy Li-like ions. The calculation removes the largest theoretical uncertainty for these transitions and yields the first experimental identification of two-loop QED effects in the region of the strong binding field. PMID- 17280350 TI - Structure and magnetization of small monodisperse platinum clusters. AB - Magnetization measurements of well-characterized monodisperse Pt clusters consisting of 13+/-2 atoms in a zeolite confirm the predicted extraordinary magnetic polarization with up to 8 unpaired electrons on a cluster, corresponding to a magnetic moment of 0.65(5) microB per atom. The effect is partly quenched by hydrogen chemisorption. The study provides insight into the electronic structure of the cluster and is fundamental for an understanding of how magnetism develops in small clusters. PMID- 17280351 TI - Experimental evidence for spin-orbit interactions in positronium-Xe collisions. AB - Spin-orbit interaction of positronium (Ps) with the surrounding atoms, predicted by Mitroy and Novikov [Phys. Rev. Lett. 90, 183202 (2003)], has been detected experimentally. We have found that the lifetime of the magnetically unperturbed ortho-Ps in Xe gas of 1 atm decreases significantly when a magnetic field of 1.0 T is applied. This decrease is attributed to the Ps spin conversion caused by spin-orbit interaction during Ps-Xe collision. The annihilation cross section of ortho-Ps due to this interaction has been determined to be 3 times as large as that expected by Mitroy and Novikov. PMID- 17280352 TI - Quantum correlations of two optical fields close to electromagnetically induced transparency. AB - We show that three-level atoms excited by two cavity modes in a Lambda configuration close to electromagnetically induced transparency can produce strongly squeezed bright beams or correlated beams which can be used for quantum nondemolition measurements. The input intensity is the experimental "knob" for tuning the system into a squeezer or a quantum nondemolition device. The quantum correlations become ideal at a critical point characterized by the appearance of a switching behavior in the mean fields intensities. Our predictions, based on a realistic fully quantum three-level model including cavity losses and spontaneous emission, allow direct comparison with future experiments. PMID- 17280353 TI - Formation of long-lived, scarlike modes near avoided resonance crossings in optical microcavities. AB - We study the formation of long-lived states near avoided resonance crossings in open systems. For three different optical microcavities (rectangle, ellipse, and semistadium) we provide numerical evidence that these states are localized along periodic rays, resembling scarred states in closed systems. Our results shed light on the morphology of long-lived states in open mesoscopic systems. PMID- 17280354 TI - Subcycle pulsed focused vector beams. AB - An accurate description of a subcycle pulsed beam (SCPB) is presented based on the complex-source model. The fields are exact solutions of Maxwell's equations and applicable to a focused pulsed beam with a pulse duration down to and below one cycle of the carrier wave and with arbitrary polarization state. Depending on the pulse duration, the pulse is blueshifted, and its wings are chirped. This effect, which we refer to as "self-induced blueshift" goes beyond the carrier envelope description. The corresponding phase is a temporal analog of the Gouy phase. The energy gain of a relativistic electron swept over by an SCPB is very sensitive to the proper form chosen to describe the pulse. PMID- 17280355 TI - Attosecond temporal gating with elliptically polarized light. AB - Temporal gating allows high accuracy time-resolved measurements of a broad range of ultrafast processes. By manipulating the interaction between an atom and an intense laser field, we extend gating into the nonlinear medium in which attosecond optical and electron pulses are generated. Our gate is an amplitude gate induced by ellipticity of the fundamental pulse. The gate modulates the spectrum of the high harmonic emission and we use the measured modulation to characterize the sub-laser-cycle dynamics of the recollision electron wave packet. PMID- 17280343 TI - Measurement of high-pT single electrons from heavy-flavor decays in p + p collisions at square root of s = 200 GeV. AB - The momentum distribution of electrons from decays of heavy flavor (charm and bottom) for midrapidity absolute value of y < 0.35 in p + p collisions at square root of s = 200 GeV has been measured by the PHENIX experiment at the BNL Relativistic Heavy Ion Collider over the transverse momentum range 0.3 < pT < 9 GeV/c. Two independent methods have been used to determine the heavy-flavor yields, and the results are in good agreement with each other. A fixed-order-plus next-to-leading-log perturbative QCD calculation agrees with the data within the theoretical and experimental uncertainties, with the data/theory ratio of 1.71+/ 0.02stat+/-0.18sys for 0.3 < pT < 9 GeV/c. The total charm production cross section at this energy has also been deduced to be sigma cc = 567+/-57stat+/ 193sys microb. PMID- 17280342 TI - Longitudinal double-spin asymmetry and cross section for inclusive jet production in polarized proton collisions at square root of s = 200 GeV. AB - We report a measurement of the longitudinal double-spin asymmetry A(LL) and the differential cross section for inclusive midrapidity jet production in polarized proton collisions at square root of s = 200 GeV. The cross section data cover transverse momenta 5 < pT < 50 GeV/c and agree with next-to-leading order perturbative QCD evaluations. The A(LL) data cover 5 < pT < 17 GeV/c and disfavor at 98% C.L. maximal positive gluon polarization in the polarized nucleon. PMID- 17280356 TI - Long-range propagation of plasmon polaritons in a thin metal film on a one dimensional photonic crystal surface. AB - We present experimental results on ultralong-range surface plasmon polaritons, propagating in a thin metal film on a one-dimensional (1D) photonic crystal surface over a distance of several millimeters. This propagation length is about 2 orders of magnitude higher than the one in the ordinary Kretschmann configuration at the same optical frequency. We show that a long-range surface plasmon polaritons propagation may take place not only in a (quasi)symmetrical scheme, where a thin metal film is located between two media with (approximately) the same refraction index, but also in a scheme where the thin metal film is located between an appropriate 1D photonic crystal and an arbitrary (air, water, etc.) medium. The ultralong-range surface plasmon polaritons are potentially important for biosensors, plasmonics, and other applications. PMID- 17280357 TI - Dissipative solitons that cannot be trapped. AB - We show that dissipative solitons in systems with high-order nonlinear dissipation cannot survive in the presence of trapping potentials of the rigid wall or asymptotically increasing type. Solitons in such systems can survive in the presence of a weak potential but only with energies out of the interval of existence of linear quantum mechanical stationary states. PMID- 17280358 TI - First experimental observation of superscars in a pseudointegrable barrier billiard. AB - With a perturbation body technique intensity distributions of the electric field strength in a flat microwave billiard with a barrier inside up to mode numbers as large as about 700 were measured. A method for the reconstruction of the amplitudes and phases of the electric field strength from those intensity distributions has been developed. Recently predicted superscars have been identified experimentally and--using the well-known analogy between the electric field strength and the quantum mechanical wave function in a two-dimensional microwave billiard--their properties determined. PMID- 17280359 TI - Reciprocal oscillons and nonmonotonic fronts in forced nonequilibrium systems. AB - The formation of oscillons in a synchronously oscillating background is studied in the context of both damped and self-exciting oscillatory media. Using the forced complex Ginzburg-Landau equation we show that such states bifurcate from finite amplitude homogenous states near the 2:1 resonance boundary. In each case we identify a region in parameter space containing a finite multiplicity of coexisting stable oscillons with different structure. Stable time-periodic monotonic and nonmonotonic frontlike states are present in an overlapping region. Both types of structure are related to the presence of a Maxwell point between the zero and finite amplitude homogeneous states. PMID- 17280360 TI - Waveguide-based off-axis holography with hard X rays. AB - We present an off-axis holography experiment based on the coherent cone beams emitted from a pair of x-ray waveguides. A magnified off-axis hologram is recorded, from which the phase of the optical transmission function of a sample is obtained by digital holographic reconstruction. A spatial resolution of about 100 nm has been achieved at 10.4 keV photon energy. Spatial resolution is determined by the cross-sectional dimensions of the waveguide and could approach a fundamental limit of about 10 nm in future experiments. In addition, we propose a new experimental setup that might overcome this limitation. PMID- 17280361 TI - Magnetic reconnection and plasma dynamics in two-beam laser-solid interactions. AB - We present measurements of a magnetic reconnection in a plasma created by two laser beams (1 ns pulse duration, 1 x 10(15) W cm(-2)) focused in close proximity on a planar solid target. Simultaneous optical probing and proton grid deflectometry reveal two high velocity, collimated outflowing jets and 0.7-1.3 MG magnetic fields at the focal spot edges. Thomson scattering measurements from the reconnection layer are consistent with high electron temperatures in this region. PMID- 17280362 TI - Dynamic alignment in driven magnetohydrodynamic turbulence. AB - Motivated by recent analytic predictions, we report numerical evidence showing that in driven incompressible magnetohydrodynamic turbulence the magnetic- and velocity-field fluctuations locally tend to align the directions of their polarizations. This dynamic alignment is stronger at smaller scales with the angular mismatch between the polarizations decreasing with the scale lambda approximately as theta(lambda) is proportional to lambda(1/4). This can naturally lead to a weakening of the nonlinear interactions and provide an explanation for the energy spectrum E(k) is proportional to k(-3/2) that is observed in numerical experiments of strongly magnetized turbulence. PMID- 17280363 TI - Strong ExB shear flows in the transport-barrier region in H-mode plasma. AB - We report the first experimental observation of stationary zonal flow in the transport-barrier region of the H-mode plasma. Strong peaks in Er shear mark the width of this region. A strong m = n = 0 low-frequency (f < 0.6 kHz) zonal flow is observed in regions of increased Er, suggesting a substantial contribution of zonal flow to the spatial modulation of Er radial profiles. Radial localization of the zonal flow is correlated with a region of zero magnetic shear and low order (7/5) rational surfaces. PMID- 17280364 TI - Direct observation of local distortion of a crystal lattice with picometer accuracy using atomic resolution neutron holography. AB - We demonstrate that neutron holography permits us to extend the determination of atomic positions beyond nearest neighbors at least up to the fourth neighboring shell around cadmium probe atoms alloyed into a lead crystal. The accuracy achieved is sufficient to allow quantitative determination of displacements of atoms due to elastic distortions induced by impurity atoms. The atomic positions derived from the holographic data are in good agreement with those expected theoretically due to Friedel oscillations in this system. In addition, the atomic positions are in qualitative agreement with results obtained in an independent experiment studying the diffuse distortion scattering around Bragg peaks. PMID- 17280365 TI - Probing the structure and energetics of dislocation cores in SiGe alloys through Monte Carlo simulations. AB - We present a methodology for the investigation of dislocation energetics in segregated alloys based on Monte Carlo simulations which equilibrate the topology and composition of the dislocation core and its surroundings. An environment dependent partitioning of the system total energy into atomic contributions allows us to link the atomistic picture to continuum elasticity theory. The method is applied to extract core energies and radii of 60 degrees glide dislocations in segregated SiGe alloys which are inaccessible by other methods. PMID- 17280366 TI - Megabar-pressure infrared study of hydrogen deuteride. AB - Solid hydrogen deuteride (HD) has been studied to a pressure of 159 GPa and to low temperatures using near infrared spectroscopy. Of the two high pressure phases observed in hydrogen and deuterium, known as the BSP (broken-symmetry phase) and the A phase, only the BSP had been observed in the lower pressure region of the phase line of HD and it was unusually different from the homonuclear diatomic species with a reentrant behavior. In this Letter the BSP phase line is identified to its maximum pressure of 159 GPa. Infrared absorption reveals a transition to the A phase, observed for the first time in HD with onset at 157+/-3 GPa. A new phase of electric dipolar order that should occur at low temperature is discussed. PMID- 17280367 TI - Electron-ion interference and Onsager reciprocity in mixed ionic-electronic transport in TiO2. AB - Onsager's reciprocity theorem has been extensively discussed for fluid systems and its validity generally accepted. The application of the theorem to solid state, however, is not always transparent due to additional complications that have no counterparts in fluids, and its validity has not been so exhaustively examined experimentally either. Here we show that in the phenomenon of mixed ionic-electronic conduction in TiO2 (rutile), the theorem is verified experimentally, and the Onsager cross coefficient can be even larger than a direct one, contrary to the conventional belief. PMID- 17280369 TI - How do oxygen molecules move into silver contacts and change their electronic transport properties? AB - We present first principles simulations of the elongation process of the silver contact at the O2 atmosphere. The electronic transport properties are calculated. It is found that the O2 molecule can move into the silver contact during elongation and the corresponding mechanism is given. We demonstrate that there are two transmission channels around the Fermi level in an Ag-O2 contact system. The breaking process of an Ag-Ag bond is found to play an important role in determining the evolution of the system conductance during the elongation. PMID- 17280368 TI - Atomistic mechanism of boron diffusion in silicon. AB - B diffuses in crystalline Si by reacting with a Si self-interstitial (I) with a frequency g and so forming a fast migrating BI complex that can migrate for an average length lambda. We experimentally demonstrate that both g and lambda strongly depend on the free hole concentration p. At low p, g has a constant trend and lambda increases with p, while at high p, g has a superlinear trend and lambda decreases with p. This demonstrates that BI forms in the two regimes by interaction with neutral and double positive I, respectively, and its charge state has to change by interaction with free holes before diffusing. PMID- 17280370 TI - Evidence of long-wavelength collective excitations in magnetic superlattices. AB - We report on a mechanism of dynamic dipolar coupling in magnetic superlattices via long-wavelength nonevanescent fields. In the spin excitation spectra of our heterophase stripe structures, such interactions mediate a singlet<-->doublet crossover in the frequency regime driven by the orientation of an external static field. This crossover is a new feature observed in collective behavior of superlattices, though there is some analogy of this phenomenon with birefringence taking place in optical superlattices. We envision applying the collective effects described here in microwave photonic devices. PMID- 17280371 TI - Energy dependence on fractional charge for strongly interacting subsystems. AB - The energies of a pair of strongly interacting subsystems with arbitrary noninteger charges are examined from closed- and open-system perspectives. An ensemble representation of the charge dependence is derived, valid at all interaction strengths. Transforming from resonance-state ionicity to ensemble charge dependence imposes physical constraints on the occupation numbers in the strong-interaction limit. For open systems, the chemical potential is evaluated using microscopic and thermodynamic models, leading to a novel correlation between ground-state charge and an electronic temperature. PMID- 17280372 TI - Fermi-edge singularity in a spin-incoherent Luttinger liquid. AB - We theoretically investigate the Fermi-edge singularity in a spin-incoherent Luttinger liquid. Both cases of finite and infinite core hole mass are explored, as well as the effect of a static external magnetic field of arbitrary strength. For a finite mass core hole the absorption edge behaves as (omega-omega th)alpha/square root of absolute value (ln(omega-omega th)) for frequencies omega just above the threshold frequency omega th. The exponent alpha depends on the interaction parameter g of the interacting one dimensional system, the electron hole coupling, and is independent of the magnetic field strength, the momentum, and the mass of the excited core hole (in contrast to the spin-coherent case). In the infinite mass limit, the spin-incoherent problem can be mapped onto an equivalent problem in a spinless Luttinger liquid for which the logarithmic factor is absent, and backscattering from the core hole leads to a universal contribution to the exponent alpha. PMID- 17280373 TI - Critical fidelity at the metal-insulator transition. AB - Using a Wigner Lorentzian random matrix ensemble, we study the fidelity, F(t), of systems at the Anderson metal-insulator transition, subject to small perturbations that preserve the criticality. We find that there are three decay regimes as perturbation strength increases: the first two are associated with a Gaussian and an exponential decay, respectively, and can be described using linear response theory. For stronger perturbations F(t) decays algebraically as F(t) approximately t(-D2(mu)), where D2(mu) is the correlation dimension of the local density of states. PMID- 17280374 TI - Detection of current-induced spins by ferromagnetic contacts. AB - Detection of current-induced spin accumulation via ferromagnetic contacts is discussed. Onsager's relations forbid that in a two-probe configuration, spins excited by currents in time-reversal symmetric systems can be detected by switching the magnetization of a ferromangetic detector contact. Nevertheless, current-induced spins can be transferred as a torque to a contact magnetization and can affect the charge currents in many-terminal configurations. We demonstrate the general concepts by solving the microscopic transport equations for the diffuse Rashba system with magnetic contacts. PMID- 17280375 TI - Bistability-mediated carrier recombination at light-induced boron-oxygen complexes in silicon. AB - A first-principles study of the BO2 complex in B-doped Czochralski Si reveals a defect-bistability-mediated carrier recombination mechanism, which contrasts with the standard fixed-level Shockley-Read-Hall model of recombination. An O2 dimer distant from B causes only weak carrier recombination, which nevertheless drives O2 diffusion under light to form the BO2 complex. Although BO2 and O2 produce nearly identical defect levels in the band gap, the recombination at BO2 is substantially faster than at O2 because the charge state of the latter inhibits the hole capture step of recombination. PMID- 17280376 TI - Spatial extent of wave functions of gate-induced hole carriers in pentacene field effect devices as investigated by electron spin resonance. AB - An electron spin resonance (ESR) method is applied to a pentacene field-effect device to investigate gate-induced hole carriers in such devices. Clear field induced ESR signals are observed, demonstrating that all of the field-injected carriers have S = 1/2 spins. Anisotropic ESR signals due to unpaired pi electrons show the molecular orientation at the interface in the devices. The spatial extent of the spin density distribution (wave function) of the carriers is evaluated from the ESR linewidth, accounting for the hyperfine structure, to be of the order of 10 molecules. PMID- 17280377 TI - Dirac and normal fermions in graphite and graphene: implications of the quantum Hall effect. AB - Spectral analysis of the Shubnikov-de Haas magnetoresistance oscillations and the quantum Hall effect (QHE) measured in quasi-2D highly oriented pyrolytic graphite (HOPG) [Phys. Rev. Lett. 90, 156402 (2003)] reveals two types of carriers: normal (massive) electrons with Berry phase 0 and Dirac-like (massless) holes with Berry phase pi. We demonstrate that recently reported integer- and semi-integer QHEs for bilayer and single-layer graphenes take place simultaneously in HOPG samples. PMID- 17280378 TI - Interaction-induced resonance in conductance and thermopower of quantum wires. AB - We study the effect of electron-electron interaction on the transport properties of short clean quantum wires adiabatically connected to reservoirs. Interactions lead to resonances in a multichannel wire at particular values of the Fermi energy. We investigate in detail the resonance in a two-channel wire. The (negative) conductance correction peaks at the resonance, and decays exponentially as the Fermi energy is tuned away, the resonance width being given by the temperature. Likewise, the thermopower shows a characteristic structure, which is surprisingly well approximated by the so-called Mott formula. Finally, fourfold splitting of the resonance in a magnetic field provides a unique signature of the effect. PMID- 17280379 TI - Nanometer scale electronic reconstruction at the interface between LaVO3 and LaVO4. AB - Electrons at interfaces, driven to minimize their free energy, are distributed differently than in bulk. This can be dramatic at interfaces involving heterovalent compounds. Here we profile an abrupt interface between V 3d2 LaVO3 and V 3d0 LaVO4 using electron energy loss spectroscopy. Although no bulk phase of LaVOx with a V 3d1 configuration exists, we find a nanometer-wide region of V 3d1 at the LaVO3/LaVO4 interface, rather than a mixture of V 3d0 and V 3d2. The two-dimensional sheet of 3d1 electrons is a prototypical electronic reconstruction at an interface between competing ground states. PMID- 17280380 TI - Edge excitations and non-Abelian statistics in the moore-read state: A numerical study in the presence of coulomb interaction and edge confinement. AB - We study the ground state and low-energy excitations of fractional quantum Hall systems on a disk at a filling fraction nu = 5/2, with Coulomb interaction and a background confining potential. We find the Moore-Read ground state is stable within a finite but narrow window in parameter space. The corresponding low energy excitations contain a fermionic branch and a bosonic branch, with widely different velocities. A short-range repulsive potential can stabilize a charge +e/4 quasihole at the center, leading to a different edge excitation spectrum due to the change of boundary conditions for Majorana fermions, clearly indicating the non-Abelian nature of the quasihole. PMID- 17280381 TI - Novel route to a finite center-of-mass momentum pairing state for superconductors: A current-driven Fulde-Ferrell-Larkin-Ovchinnikov state. AB - The previously studied Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state is stabilized by a magnetic field via the Zeeman coupling in spin-singlet superconductors. Here we suggest a novel route to achieve nonzero center-of-mass momentum pairing states in superconductors with Fermi surface nesting. We investigate two-dimensional superconductors under a uniform external current, proportional to a finite pair momentum of q(e). We find that an FFLO state with a spontaneous pair momentum of q(s) is stabilized above a certain critical current that depends on the direction of the external current. A finite q(s) arises in order to make the total pair-momentum of q(t)(=q(s) + q(e)) perpendicular to the nesting vector, which is independent of spin states of Cooper pairs. We also discuss experimental signatures of the FFLO state. PMID- 17280382 TI - Crossover between channeling and pinning at twin boundaries in YBa2Cu3O7 thin films. AB - The critical current (Jc) of highly twinned YBa2Cu3O7 films has been measured as a function of temperature, magnetic field, and angle. For much of the parameter space we observe a strong suppression of Jc for fields in the twin boundary (TB) directions; this is quantitatively modeled as flux-cutting-mediated vortex channeling. For certain temperatures and fields a crossover occurs to a regime in which channeling is blocked and the TBs act as planar pinning centers so that TB pinning enhances the overall Jc. In this regime, intrinsic pinning along the TBs is comparable to that between the twins. PMID- 17280383 TI - Quantum cascade phenomenon in Bi2Sr2CaCu2O(8+delta) single crystals. AB - We study interlayer transport in Bi2Sr2CaCu2O(8+delta) cuprates, which represent stacks of atomic scale intrinsic Josephson junctions. A series of resonant dips in conductance is observed at condition when bremsstrahlung and recombination bands in nonequilibrium spectrum of Josephson junctions overlap. The phenomenon is explained in terms of self-detection of a new type of collective strongly nonequilibrium state in natural atomic superlattices, bearing certain resemblance with operation of a quantum cascade laser. Conclusions are supported by in situ generation-detection experiments and by numerical simulations. PMID- 17280384 TI - Antiferromagnetism and superconductivity in layered organic conductors: Variational cluster approach. AB - The kappa-(ET)2X layered conductors (where ET stands for BEDT-TTF) are studied within the dimer model as a function of the diagonal hopping t' and Hubbard repulsion U. Antiferromagnetism and d-wave superconductivity are investigated at zero temperature using variational cluster perturbation theory (VCPT). For large U, Neel antiferromagnetism exists for t' < t(c2)', with t(c2)' approximately 0.9. For fixed t', as U is decreased (or pressure increased), a d(x2-y2) superconducting phase appears. When U is decreased further, then a d(xy) order takes over. There is a critical value of t(c1)' approximately 0.8 of t' beyond which the AF and dSC phases are separated by the Mott disordered phase. PMID- 17280385 TI - Enhancement of pairwise entanglement via Z2 symmetry breaking. AB - We study the effect of symmetry breaking in a quantum phase transition on pairwise entanglement in spin-1/2 models. We give a set of conditions on correlation functions a model has to meet in order to keep the pairwise entanglement unchanged by a parity symmetry breaking. It turns out that all mean field solvable models do meet this requirement, whereas the presence of strong correlations leads to a violation of this condition. This results in an order induced enhancement of entanglement, and we report on two examples where this takes place. PMID- 17280387 TI - Loss separation for dynamic hysteresis in ferromagnetic thin films. AB - We develop a theory for dynamic hysteresis in ferromagnetic thin films, on the basis of the phenomenological principle of loss separation. We observe that, remarkably, the theory of loss separation, originally derived for bulk metallic materials, is applicable to disordered magnetic systems under fairly general conditions regardless of the particular damping mechanism. We confirm our theory both by numerical simulations of a driven random-field Ising model, and by reexamining several experimental data reported in the literature on dynamic hysteresis in thin films. All the experiments examined and the simulations find a natural interpretation in terms of loss separation. The power losses' dependence on the driving field rate predicted by our theory fits satisfactorily all the data in the entire frequency range, thus reconciling the apparent lack of universality observed in different materials. PMID- 17280386 TI - Observation of higher-harmonic helical spin-resonance modes in the chromium spinel CdCr2O4. AB - High frequency ESR measurements on the chromium spinel compound CdCr2O4 have been performed. The observed ESR modes below Hc' approximately 5.7 T can be explained well by the calculated resonance modes based on a molecular field theory assuming a helical spin structure. Other than the fundamental ones, we have succeeded in observing the higher-harmonic modes for the first time. A large change of the ESR modes above Hc' indicate that a variation of the spin structure from the helical to the four-sublattice canted one takes place around Hc'. PMID- 17280388 TI - Octupolar order in the multiple spin exchange model on a triangular lattice. AB - We show how a gapless spin liquid with hidden octupolar order arises in an applied magnetic field, in a model applicable to thin films of 3He with competing ferromagnetic and antiferromagnetic (cyclic) exchange interactions. Evidence is also presented for nematic--i.e., quadrupolar--correlations bordering on ferromagnetism in the absence of a magnetic field. PMID- 17280389 TI - Kagome ice state in the dipolar spin ice Dy2Ti2O7. AB - We have investigated the kagome ice behavior of the dipolar spin-ice compound Dy2Ti2O7 in a magnetic field along a [111] direction using neutron scattering and Monte Carlo simulations. The spin correlations show that the kagome ice behavior predicted for the nearest-neighbor interacting model, where the field induces dimensional reduction and spins are frustrated in each two-dimensional kagome lattice, occurs in the dipole interacting system. The spins freeze at low temperatures within the macroscopically degenerate ground states of the nearest neighbor model. PMID- 17280390 TI - Short period magnetic coupling oscillations in Co/Si multilayers: Theory versus experiment. AB - Today the magnetic properties of multilayers and nanostructures including a metal or an insulator as a nonmagnetic spacer layer are rather well understood. But they are much more controversial for semiconductor spacers. For instance, for Co/Si multilayers short period coupling oscillations are predicted by ab initio computations but have yet to be observed. Here we show in Co/Si multilayers prepared at low temperature (90 K) strong saturation field oscillations that are consistent with the predicted coupling oscillations. However, the decay length of the oscillations is much longer than the expected one and cannot be explained within the framework of available theories. PMID- 17280391 TI - Exciton localization of single-walled carbon nanotubes revealed by femtosecond excitation correlation spectroscopy. AB - Photoluminescence (PL) dynamics in single-walled carbon nanotubes (SWNTs) has been studied by the femtosecond excitation correlation method with a 150 fs time resolution. The SWNT samples were synthesized by different methods and suspended in gelatin films or D2O solutions. The PL dynamics of SWNTs depends on the local environment surrounding the SWNTs rather than the synthesis methods. The very weak temperature dependence of tauPL and the environment-dependent tauPL reveal that the PL relaxation process is dominated by the interplay between free excitons and weakly localized excitons. PMID- 17280392 TI - NMR evidence for higher-order multipole order parameters in NpO2. AB - We report a microscopic investigation of multipolar order parameters in the ordered state of NpO2 conducted via 17O NMR on a single crystal. From the angular dependence of hyperfine fields at 17O nuclei, we have obtained clear evidence for the appearance of field-induced antiferro-octupolar as well as field-induced antiferro-dipolar moments below T0 = 26 K. We have also observed oscillatory spin echo decay, which is well understood in terms of small electric field gradients created by antiferro-quadrupolar ordering. This reveals that the quadrupolar order parameter is directly observable by means of NMR. The present NMR studies provide definitive support for a proposed longitudinal triple-q type octupolar quadrupolar ordering model for NpO2. PMID- 17280393 TI - Multiferroic domain dynamics in strained strontium titanate. AB - Multiferroicity can be induced in strontium titanate by applying biaxial strain. Using optical second harmonic generation, we report a transition from 4/mmm to the ferroelectric mm2 phase, followed by a transition to a ferroelastic ferroelectric mm2 phase in a strontium titanate thin film. Piezoelectric force microscopy is used to study ferroelectric domain switching. Second harmonic generation, combined with phase-field modeling, is used to reveal the mechanism of coupled ferroelectric-ferroelastic domain wall motion. These studies have relevance to multiferroics with coupled polar and axial phenomena. PMID- 17280394 TI - Evidence of simultaneous double-electron promotion in F+ collisions with surfaces. AB - A high-flux beam of mass-filtered F+ at low energy (100-1300 eV) was scattered off Al and Si surfaces to study core-level excitations of F0 and F+. Elastic scattering behavior for F+ was observed at energies <300 (500) eV off Al (Si) for a 90 degrees lab angle. However, above this energy threshold, orbital mixing in the hard collision step results in electronic excitation of F via molecular orbital promotion along the 4f sigma (F-2p), significantly reducing the observed ion exit energy. In addition, despite the electronegativity of F, scattering at energies >450 (700) eV off Al (Si) produces F2+-behavior which is remarkably similar to Ne+ off the same surfaces. Inelasticities measured for single collision events agree well with the energy deficits required to form (doubly excited) F** and F+** states from F0 and F+, respectively; these excited species most likely decay to inelastic F+ and F2+ via autoionization. PMID- 17280395 TI - Critical scaling in linear response of frictionless granular packings near jamming. AB - We study the origin of the scaling behavior in frictionless granular media above the jamming transition by analyzing their linear response. The response to local forcing is non-self-averaging and fluctuates over a length scale that diverges at the jamming transition. The response to global forcing becomes increasingly nonaffine near the jamming transition. This is due to the proximity of floppy modes, the influence of which we characterize by the local linear response. We show that the local response also governs the anomalous scaling of elastic constants and contact number. PMID- 17280396 TI - Diffusion and segmental dynamics of double-stranded DNA. AB - Diffusion and segmental dynamics of the double-stranded lambda-phage DNA polymer are quantitatively studied over the transition range from stiff to semiflexible chains. Spectroscopy of fluorescence fluctuations of single-end fluorescently labeled monodisperse DNA fragments unambiguously shows that double-stranded DNA in the length range of 10(2) - 2 x 10(4) base pairs behaves as a semiflexible polymer with segmental dynamics controlled by hydrodynamic interactions. PMID- 17280397 TI - Hydra molecular network reaches criticality at the symmetry-breaking axis defining moment. AB - We study biological, multicellular symmetry breaking on a hollow cell sphere as it occurs during hydra regeneration from a random cell aggregate. We show that even a weak temperature gradient directs the axis of the regenerating animal--but only if it is applied during the symmetry-breaking moment. We observe that the spatial distribution of the early expressed, head-specific gene ks1 has become scale-free and fractal at that point. We suggest the self-organized critical state to reflect long range signaling, which is required for axis definition and arises from cell next-neighbor communication. PMID- 17280398 TI - Coevolution of strategy and structure in complex networks with dynamical linking. AB - We introduce a model in which individuals differ in the rate at which they seek new interactions with others, making rational decisions modeled as general symmetric two-player games. Once a link between two individuals has formed, the productivity of this link is evaluated. Links can be broken off at different rates. We provide analytic results for the limiting cases where linking dynamics is much faster than evolutionary dynamics and vice versa, and show how the individual capacity of forming new links or severing inconvenient ones maps into the problem of strategy evolution in a well-mixed population under a different game. For intermediate ranges, we investigate numerically the detailed interplay determined by these two time scales and show that the scope of validity of the analytical results extends to a much wider ratio of time scales than expected. PMID- 17280399 TI - Bistable bacterial growth rate in response to antibiotics with low membrane permeability. AB - We demonstrate that growth rate bistability for bacterial cells growing exponentially at a fixed external antibiotic concentration can emerge when the cell wall permeability for the drug is low and the growth rate sensitivity to the intracellular drug concentration is high. Under such conditions, an initially high growth rate can remain high, due to dilution of the intracellular drug concentration by rapid cell volume increase, while an initially low growth rate can remain low, due to slow cell volume increase and insignificant drug dilution. Our findings have implications for the testing of novel antibiotics on growing bacterial strains. PMID- 17280401 TI - Nonlinear screening and gas-liquid separation in suspensions of charged colloids. AB - We calculate phase diagrams of charged colloidal spheres (valency Z and radius a) in a 1:1 electrolyte from multicentered nonlinear Poisson-Boltzmann theory. Our theory takes into account charge renormalization of the colloidal interactions and volume terms due to many-body effects. For valencies as small as Z = 1 and as large as 10(4) we find a gas-liquid spinodal instability in the colloid-salt phase diagram provided Z lambdaB/a > or similar 24+/-1, where lambdaB is the Bjerrum length. PMID- 17280400 TI - Mechanisms of molecular response in the optimal control of photoisomerization. AB - We report on adaptive feedback control of photoinduced barrierless isomerization of 1,1'-diethyl-2,2'-cyanine in solution. We compare the effect of different fitness parameters and show that optimal control of the absolute yield of isomerization (photoisomer concentration versus excitation photons) can be achieved, while the relative isomerization yield (photoisomer concentration versus number of relaxed excited-state molecules) is unaffected by adaptive feedback control. The temporal structure of the optimized excitation pulses allows one to draw clear mechanistic conclusions showing the critical importance of coherent nuclear motion for the control of isomerization. PMID- 17280402 TI - Collective rearrangement at the onset of flow of a polycrystalline hexagonal columnar phase. AB - Creep experiments on polycrystalline surfactant hexagonal columnar phases show a power law regime, followed by a drastic fluidization before reaching a final stationary flow. The scaling of the fluidization time with the shear modulus of the sample and stress applied suggests that the onset of flow involves a bulk reorganization of the material. This is confirmed by x-ray scattering under stress coupled to in situ rheology experiments, which show a collective reorientation of all crystallites at the onset of flow. The analogy with the fracture of heterogeneous materials is discussed. PMID- 17280403 TI - Comment on "Rontgen quantum phase shift: a semiclassical local electrodynamical effect?". PMID- 17280405 TI - Comment on "Atomic origin of magnetocrystalline anisotropy in Nd2Fe14B". PMID- 17280407 TI - Hidden order in 1D bose insulators. AB - We investigate the phase diagram of spinless bosons with long range (variant 1/r(3)) repulsive interactions, relevant to ultracold polarized atoms or molecules, using density matrix renormalization group. Between the two conventional insulating phases, the Mott and density wave phases, we find a new phase possessing hidden order revealed by nonlocal string correlations analogous to those characterizing the Haldane gapped phase of integer spin chains. We develop a mean field theory that describes the low-energy excitations in all three insulating phases. This is used to calculate the absorption spectrum due to oscillatory lattice modulation. We predict a sharp resonance in the spectrum due to a collective excitation of the new phase that would provide clear evidence for the existence of this phase. PMID- 17280408 TI - Continuous and pulsed quantum zeno effect. AB - Continuous and pulsed quantum Zeno effects were observed using a 87Rb Bose Einstein condensate. Oscillations between two ground hyperfine states of a magnetically trapped condensate, externally driven at a transition rate omega(R), were suppressed by destructively measuring the population in one of the states with resonant light. The suppression of the transition rate in the two-level system was quantified for pulsed measurements with a time interval deltat between pulses and continuous measurements with a scattering rate gamma. We observe that the continuous measurements exhibit the same suppression in the transition rate as the pulsed measurements when gammadeltat=3.60(0.43), in agreement with the predicted value of 4. Increasing the measurement rate suppressed the transition rate down to 0.005 omega(R). PMID- 17280409 TI - Bogoliubov-Cerenkov radiation in a Bose-Einstein condensate flowing against an obstacle. AB - We study the density modulation that appears in a Bose-Einstein condensate flowing with supersonic velocity against an obstacle. The experimental density profiles observed at JILA are reproduced by a numerical integration of the Gross Pitaevskii equation and then interpreted in terms of Cerenkov emission of Bogoliubov excitations by the defect. The phonon and the single-particle regions of the Bogoliubov spectrum are, respectively, responsible for a conical wave front and a fan-shaped series of precursors. PMID- 17280410 TI - Computational difficulty of global variations in the density matrix renormalization group. AB - The density matrix renormalization group approach is arguably the most successful method to numerically find ground states of quantum spin chains. It amounts to iteratively locally optimizing matrix-product states, aiming at better and better approximating the true ground state. To date, both a proof of convergence to the globally best approximation and an assessment of its complexity are lacking. Here we establish a result on the computational complexity of an approximation with matrix-product states: The surprising result is that when one globally optimizes over several sites of local Hamiltonians, avoiding local optima, one encounters in the worst case a computationally difficult NP-hard problem (hard even in approximation). The proof exploits a novel way of relating it to binary quadratic programming. We discuss intriguing ramifications on the difficulty of describing quantum many-body systems. PMID- 17280411 TI - Entangled three-qubit states without concurrence and three-tangle. AB - We provide a complete analysis of mixed three-qubit states composed of a Greenberger-Horne-Zeilinger state and a W state orthogonal to the former. We present optimal decompositions and convex roofs for the three-tangle. Further, we provide an analytical method to decide whether or not an arbitrary rank-2 state of three qubits has vanishing three-tangle. These results highlight intriguing differences compared to the properties of two-qubit mixed states, and may serve as a quantitative reference for future studies of entanglement in multipartite mixed states. By studying the Coffman-Kundu-Wootters inequality we find that, while the amounts of inequivalent entanglement types strictly add up for pure states, this "monogamy" can be lifted for mixed states by virtue of vanishing tangle measures. PMID- 17280412 TI - Fluorescence near-field microscopy of DNA at sub-10 nm resolution. AB - We demonstrate apertureless near-field microscopy of single molecules at sub-10 nm resolution. With a novel phase filter, near-field images of single organic fluorophores were obtained with approximately sixfold improvement in the signal to-noise ratio. The improvement allowed pairs of molecules separated by approximately 15 nm to be reliably and repeatedly resolved, thus demonstrating the first true Rayleigh resolution test for near-field images of single molecules. The potential of this technique for biological applications was demonstrated with an experiment that measured the helical rise of A-form DNA. PMID- 17280413 TI - 21-cm background anisotropies can discern primordial non-Gaussianity. AB - The non-Gaussianity of initial perturbations provides information on the mechanism that generated primordial density fluctuations. We find that 21-cm background anisotropies due to inhomogeneous neutral hydrogen distribution prior to reionization captures information on primordial non-Gaussianity better than a high-resolution cosmic microwave background anisotropy map. An all-sky 21-cm experiment over the frequency range from 14 to 40 MHz with angular information out to a multipole of 10(5) can limit the primordial non-Gaussianity parameter f(NL) <, similar 0.01. PMID- 17280414 TI - Strategy for searching for a dark matter sterile neutrino. AB - We propose a strategy for how to look for dark matter particles possessing a radiative decay channel and derive constraints on their parameters from observations of x rays from our own Galaxy and its dwarf satellites. When applied to sterile neutrinos in the keV mass range this approach gives a significant improvement to restrictions on neutrino parameters compared with previous works. PMID- 17280415 TI - Compactified strings as quantum statistical partition function on the Jacobian torus. AB - We show that the solitonic contribution of toroidally compactified strings corresponds to the quantum statistical partition function of a free particle living on higher dimensional spaces. In the simplest case of compactification on a circle, the Hamiltonian is the Laplacian on the 2g-dimensional Jacobian torus associated with the genus g Riemann surface corresponding to the string world sheet. T duality leads to a symmetry of the partition function mixing time and temperature. Such a classical-quantum correspondence and T duality shed some light on the well-known interplay between time and temperature in quantum field theory and classical statistical mechanics. PMID- 17280417 TI - Seeing an invisible axion in the supersymmetric particle spectrum. AB - I describe how under favorable circumstances, the existence of an invisible axion could correlate with a distinctive CERN Large Hadron Collider sparticle spectrum, in particular, through a gluino approximately ln(M(P)/m(3/2)) times heavier than other gauginos. PMID- 17280419 TI - Anomalous enhancement of a penguin hadronic matrix element in B-->K(eta'). AB - We estimate the density matrix element for the pi(0), eta, and eta(') production from the vacuum in the large-N(c) limit. As a consequence, we find that the QCD axial anomaly leads to highly nontrivial corrections to the usual flavor SU(3) relations between B(0)-->K(0)pi(0), B(0)-->K(0) eta, and B(0)-->K(0)eta(') decay amplitudes. These corrections may explain why the B-->Keta(') branching ratio is about 6 times larger than the B-->Kpi one. PMID- 17280422 TI - Role of the gouy phase in the coherent phase control of the photoionization and photodissociation of vinyl chloride. AB - We demonstrate theoretically and experimentally that the Gouy phase of a focused laser beam may be used to control the photoinduced reactions of a polyatomic molecule. Quantum mechanical interference between one- and three-photon excitation of vinyl chloride produces a small phase lag between the dissociation and ionization channels on the axis of the molecular beam. Away from the axis, the Gouy phase introduces a much larger phase lag that agrees quantitatively with theory without any adjustable parameters. PMID- 17280423 TI - Frequency-resolved optical gating of isolated attosecond pulses in the extreme ultraviolet. AB - The pulse shape and phase of isolated attosecond extreme ultraviolet (XUV) pulses with a duration of 860 asec have been determined simultaneously by using frequency-resolved optical gating based on two-photon above-threshold ionization with 28-eV photons in He. From the detailed characterization, we succeeded in shaping isolated XUV pulses on an attosecond time scale by precise dispersion control with Ar gas density or by changing the driving pulse width. These results offer a novel way to excite and observe an electron motion in atoms and molecules. PMID- 17280421 TI - Scaling tests of the cross section for deeply virtual Compton scattering. AB - We present the first measurements of the e[over -->]p-->epgamma cross section in the deeply virtual Compton scattering (DVCS) regime and the valence quark region. The Q(2) dependence (from 1.5 to 2.3 GeV(2)) of the helicity-dependent cross section indicates the twist-2 dominance of DVCS, proving that generalized parton distributions (GPDs) are accessible to experiment at moderate Q(2). The helicity independent cross section is also measured at Q(2)=2.3 GeV(2). We present the first model-independent measurement of linear combinations of GPDs and GPD integrals up to the twist-3 approximation. PMID- 17280424 TI - Anomalous light scattering by small particles. AB - Light scattering by a small spherical particle with a low dissipation rate is discussed based upon the Mie theory. It is shown that if close to the plasmon (polariton) resonance frequencies the radiative damping prevails over dissipative losses, sharp giant resonances with very unusual properties may be observed. In particular, the resonance extinction cross section increases with an increase in the order of the resonance (dipole, quadrupole, etc.); the characteristic values of electric and magnetic near fields for the scattered light are singular in the particle size, while energy circulation in the near field is rather complicated, so that the Poynting vector field includes singular points whose number, types, and positions are very sensitive to fine changes in the incident light frequency. The results may provide new opportunities for a giant, controlled, highly frequency-sensitive enhancement and variation of electromagnetic field at nanoscales. PMID- 17280425 TI - Quantum scaling laws in the onset of dynamical delocalization. AB - We study the destruction of dynamical localization experimentally observed in an atomic realization of the kicked rotor by a deterministic Hamiltonian perturbation, with a temporal periodicity incommensurate with the principal driving. We show that the destruction is gradual, with well-defined scaling laws for the various classical and quantum parameters, in sharp contrast to predictions based on the analogy with Anderson localization. PMID- 17280426 TI - Manifestations of drag reduction by polymer additives in decaying, homogeneous, isotropic turbulence. AB - The existence of drag reduction by polymer additives, well established for wall bounded turbulent flows, is controversial in homogeneous, isotropic turbulence. To settle this controversy, we carry out a high-resolution direct numerical simulation of decaying, homogeneous, isotropic turbulence with polymer additives. Our study reveals clear manifestations of drag-reduction-type phenomena: On the addition of polymers to the turbulent fluid, we obtain a reduction in the energy dissipation rate, a significant modification of the fluid energy spectrum especially in the deep-dissipation range, a suppression of small-scale intermittency, and a decrease in small-scale vorticity filaments. PMID- 17280427 TI - Self-assembly of particles for densest packing by mechanical vibration. AB - It is shown that by properly controlling vibrational and charging conditions, the transition from disordered to ordered, densest packing of particles can be obtained consistently. The method applies to both spherical and nonspherical particles. For spheres, face centered cubic packing with different orientations can be achieved by monitoring the vibration amplitude and frequency, and the structure of the bottom layer, in particular. The resultant force structures are ordered but do not necessarily correspond to the packing structures fully. The implications of the findings are also discussed. PMID- 17280420 TI - Measurements of the continuum R(uds) and R values in e(+)e(-) annihilation in the energy region between 3.650 and 3.872 GeV. AB - We report measurements of the continuum R(uds) near the center-of-mass energy of 3.70 GeV, the R[uds(c)+psi(3770)](s) and the R(had)(s) values in e(+)e(-) annihilation at 68 energy points in the energy region between 3.650 and 3.872 GeV with the BES-II detector at the BEPC Collider. We obtain the R(uds) for the continuum light hadron (containing u, d, and s quarks) production near the DD threshold to be R(uds)=2.141+/-0.025+/-0.085. PMID- 17280428 TI - Contribution of slow clusters to the bulk elasticity near the colloidal glass transition. AB - We use confocal microscopy to visualize individual particles near the colloidal glass transition. We identify the most slowly-relaxing particles and show that they form spatially correlated clusters that percolate across the sample. In supercooled fluids, the largest cluster spans the system on short time scales but breaks up on longer time scales. In contrast, in glasses, a percolating cluster exists on all accessible time scales. Using molecular dynamics simulation, we show that these clusters make the dominant contribution to the bulk elasticity of the sample. PMID- 17280429 TI - Measurement of effective temperatures in an aging colloidal glass. AB - We study the thermal fluctuations of an optically confined probe particle, suspended in an aging colloidal suspension, as the suspension transforms from a viscous liquid into an elastic glass. The micron-sized bead forms a harmonic oscillator. By monitoring the equal-time fluctuations of the tracer, at two different laser powers we determine the temperature of the oscillator, T(o). In the ergodic liquid the temperatures of the oscillator and its environment are equal, while in contrast, in a nonequilibrium glassy phase we find that T(o) substantially exceeds the bath temperature. PMID- 17280430 TI - How water meets a hydrophobic surface. AB - Synchrotron x-ray reflectivity measurements of the interface between water and methyl-terminated octadecylsilane monolayers with stable contact angle >100 degrees conclusively show a depletion layer, whether or not the water is degassed. The thickness is of order one water molecule: 2-4 Angstrom with electron density <40% that of bulk water. Considerations of coherent and incoherent averaging of lateral inhomogeneities show that the data cannot be explained by "nanobubbles." When the contact angle is lower, unstable in time, or when monolayers fail to be sufficiently smooth over the footprint of the x-ray beam, there is no recognizable depletion. PMID- 17280431 TI - Quantum size effect on adatom surface diffusion. AB - Using scanning tunneling microscopy, we demonstrate that the nucleation density of Fe islands on the surface of nanoscale Pb films oscillates with the film thickness, providing a direct manifestation of the quantum size effect on surface diffusion. The Fe adatom diffusion barriers were derived to be 204+/-5 and 187+/ 5 meV on a 21 and 26 monolayer (ML) Pb film, respectively, by matching the kinetic Monte Carlo simulations to the experimental island densities. The effect is further illustrated by the growth of Fe islands on wedged Pb films, where the Fe island density is consistently higher on the odd-layer films than on the even layer films in the thickness range of 11 to 15 ML. PMID- 17280432 TI - Surface exchange and shape transitions of PbSe quantum dots during overgrowth. AB - Epitaxial overgrowth of PbSe quantum dots is shown to drastically affect their shape and composition due to anion exchange reactions. As shown by scanning tunneling microscopy, for PbTe capping layers this results in a complete truncation of the dots. Introduction of EuTe into the cap layer leads to an effective suppression of the anion exchange process. This preserves the original dot pyramids and induces a large stress concentration on the surface which further alters the overgrowth process. PMID- 17280433 TI - Dynamics and energetics of Ge(001) dimers. AB - The dynamic behavior of surface dimers on Ge(001) has been studied by positioning the tip of a scanning tunneling microscope over single flip-flopping dimers and measuring the tunneling current as a function of time. We observe that not just symmetric, but also asymmetric appearing dimers exhibit flip-flop motion. The dynamics of flip-flopping dimers can be used to sensitively gauge the local potential landscape of the surface. Through a spatial and time-resolved measurement of the flip-flop frequency of the dimers, local strain fields near surface defects can be accurately probed. PMID- 17280434 TI - Reduced viscosity in thin polymer films. AB - The dewetting of thin polystyrene films (20-500 nm) on a liquid substrate is studied at time scales that are long compared to the reptation time. It is shown that the kinetics correspond to those of purely viscous flow and that the viscosity measured by this technique is, for the thickest films, consistent with bulk measurements. Films on the order of the coil size are then studied. The effective viscosity of these films displays a large decrease when the film thickness h is below several radius of gyration, R(g). This viscosity reduction is found to depend only on the ratio h/R(g). PMID- 17280436 TI - Monoclinic and correlated metal phase in VO(2) as evidence of the Mott transition: coherent phonon analysis. AB - In femtosecond pump-probe measurements, the appearance of coherent phonon oscillations at 4.5 and 6.0 THz indicating the rutile metal phase of VO2 does not occur simultaneously with the first-order metal-insulator transition (MIT) near 68 degrees C. The monoclinic and correlated metal (MCM) phase between the MIT and the structural phase transition (SPT) is generated by a photoassisted hole excitation, which is evidence of the Mott transition. The SPT between the MCM phase and the rutile metal phase occurs due to subsequent Joule heating. The MCM phase can be regarded as an intermediate nonequilibrium state. PMID- 17280435 TI - Sample preserving deep interface characterization technique. AB - We propose a nondestructive technique based on atomic core-level shifts to characterize the interface quality of thin film nanomaterials. Our method uses the inherent sensitivity of the atomic core-level binding energies to their local surroundings in order to probe the layer-resolved binary alloy composition profiles at deeply embedded interfaces. From an analysis based upon high energy x ray photoemission spectroscopy and density functional theory of a Ni/Cu fcc (100) model system, we demonstrate that this technique is a sensitive tool to characterize the sharpness of a buried interface. We performed controlled interface tuning by gradually approaching the diffusion temperature of the multilayer, which lead to intermixing. We show that core-level spectroscopy directly reflects the changes in the electronic structure of the buried interfaces, which ultimately determines the functionality of the nanosized material. PMID- 17280437 TI - Linear-scaling density matrix perturbation treatment of electric fields in solids. AB - We develop a novel linear-scaling [O(N)] algorithm for calculating the optical dielectric constant and Born effective charge. Our method relies on the fact that only the sum of the nondiagonal parts of the electric field perturbation in solids contributes to the first-order derivative density matrix, which can then be obtained through the density-matrix perturbation method. The optical dielectric constant of amorphous SiO(2) is computed using a realistic model for the first time. PMID- 17280438 TI - Calculation of magnetic exchange interactions in Mott-Hubbard systems. AB - An efficient method of computing magnetic exchange interactions in systems with strong correlations is introduced. It is based on a magnetic force theorem that evaluates linear response due to rotations of magnetic moments and uses a generalized spectral density functional framework allowing us to explore several approximations ranging from local density functional to exact diagonalization based dynamical mean field theory. Applications to spin waves and magnetic transition temperatures of 3d metal mono-oxides as well as high-T(c) superconductors are in good agreement with experiment. PMID- 17280416 TI - Measurements of branching fraction, polarization, and charge asymmetry of B(+/-)- >rho(+/-)rho(0) and a search for B(+/-)-->rho(+/-)f(0)(980). AB - We measure the branching fraction (B), polarization (f(L)), and CP asymmetry (A(CP)) of B(+/-)-->rho(+/-)rho(0) decays and search for the decay B(+/-)- >rho(+/-)f(0)(980) based on a data sample of 231.8 x 10(6) Upsilon(4S)-->BB decays collected with the BABAR detector at the SLAC PEP-II asymmetric-energy B factory. In B(+/-)-->rho(+/-)rho(0) decays we measure B=(16.8+/-2.2+/-2.3) x 10( ), f(L)=0.905+/-0.042(-0.027)(+0.023), and A(CP)=-0.12+/-0.13+/-0.10, and find an upper limit on the branching fraction of B(+/-)-->rho(+/-)f(0)(980)(-->pi(+)pi( )) decays of 1.9 x 10(-6) at 90% confidence level. PMID- 17280439 TI - Evidence of collective charge transport in the ohmic regime of o-TaS(3) in the charge-density-wave state by a photoconduction study. AB - Using photoconduction techniques, we demonstrate that the low-temperature Ohmic conduction of o-TaS3 is not provided by band motion or hopping of single-particle excitations-electrons and holes excited over the Peierls gap. Instead, the low temperature Ohmic conduction is mostly provided by collective excitations having an activation energy much less than the Peierls gap value and shunting the contribution of electrons and holes responsible for photoconduction. PMID- 17280440 TI - Landau level spectroscopy of ultrathin graphite layers. AB - Far infrared transmission experiments are performed on ultrathin epitaxial graphite samples in a magnetic field. The observed cyclotron resonance-like and electron-positron-like transitions are in excellent agreement with the expectations of a single-particle model of Dirac fermions in graphene, with an effective velocity of c=1.03 x 10(6) m/s. PMID- 17280441 TI - Thermoplasma polariton within scaling theory of single-layer graphene. AB - The electrodynamics of single-layer graphene is studied in the scaling regime. At any finite temperature, there is a weakly damped collective thermoplasma polariton mode whose dispersion and wavelength-dependent damping is determined analytically. The electric and magnetic fields associated with this mode decay exponentially in the direction perpendicular to the graphene layer, but, unlike the surface plasma polariton modes of metals, the decay length and the mode frequency are strongly temperature-dependent. This may lead to new ways of generation and manipulation of these modes. PMID- 17280442 TI - Nonadiabatic Kohn anomaly in a doped graphene monolayer. AB - We compute, from first principles, the frequency of the E(2g), Gamma phonon (Raman G band) of graphene, as a function of the charge doping. Calculations are done using (i) the adiabatic Born-Oppenheimer approximation and (ii) time dependent perturbation theory to explore dynamic effects beyond this approximation. The two approaches provide very different results. While the adiabatic phonon frequency weakly depends on the doping, the dynamic one rapidly varies because of a Kohn anomaly. The adiabatic approximation is considered valid in most materials. Here, we show that doped graphene is a spectacular example where this approximation miserably fails. PMID- 17280418 TI - Observation of B(+)-->phiphiK(+) and evidence for B(0)-->phiphiK(0) below eta(c) threshold. AB - We report measurements of the decays B(+)-->phiphiK(+) and B(0)-->phiphiK(0) using a sample of 231 x 10(6) BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy B factory at the Stanford Linear Accelerator Center. The branching fractions are measured to be B(B(+)-->phiphiK(+))=(7.5+/-1.0(stat)+/ 0.7(syst)) x 10(-6) and B(B(0)-->phiphiK(0))=(4.1(-1.4)(+1.7)(stat)+/-0.4(syst)) x 10(-6) for a phiphi invariant mass below 2.85 GeV/c(2). PMID- 17280443 TI - Nonequilibrium dynamical mean-field theory. AB - The many-body formalism for dynamical mean-field theory is extended to treat nonequilibrium problems. We illustrate how the formalism works by examining the transient decay of the oscillating current that is driven by a large electric field turned on at time t=0. We show how the Bloch oscillations are quenched by the electron-electron interactions, and how their character changes dramatically for a Mott insulator. PMID- 17280444 TI - Spin-Hall effect in a [110] GaAs quantum well. AB - A self-consistent treatment of the spin-Hall effect requires consideration of the spin-orbit coupling and electron-impurity scattering on equal footing. This is done here for the experimentally relevant case of a [110] GaAs quantum well [Sih, Nature Phys. 1, 31 (2005)]. Working within the framework of the exact linear response formalism we calculate the spin-Hall conductivity including the Dresselhaus linear and cubic terms in the band structure, as well as the electron impurity scattering and electron-electron interaction to all orders. We show that the spin-Hall conductivity naturally separates into two contributions, skew scattering and side-jump, and we propose an experiment to distinguish between them. PMID- 17280445 TI - Shot noise in magnetic tunnel junctions: evidence for sequential tunneling. AB - We report the experimental observation of sub-Poissonian shot noise in single magnetic tunnel junctions, indicating the importance of tunneling via impurity levels inside the tunnel barrier. For junctions with weak zero-bias anomaly in conductance, the Fano factor (normalized shot noise) depends on the magnetic configuration being enhanced for antiparallel alignment of the ferromagnetic electrodes. We propose a model of sequential tunneling through nonmagnetic and paramagnetic impurity levels inside the tunnel barrier to qualitatively explain the observations. PMID- 17280446 TI - Manipulation of the Kondo effect via two-dimensional molecular assembly. AB - We report the manipulation of a Kondo resonance originating from the spin electron interactions between a two-dimensional molecular assembly of TBrPP-Co molecules and a Cu(111) surface at 4.6 K. By manipulating nearest-neighbor molecules with a scanning tunneling microscope tip we are able to tune the spin electron coupling of the center molecule inside a hexagonal molecular assembly in a controlled step-by-step manner. The Kondo temperature increases from 105 to 170 K with decreasing the number of nearest neighbor molecules from six to zero. The scattering of surface electrons by the molecules located at edges of the molecular layer reduces the spin-electron coupling strength for the molecules inside the layer. Investigations of different molecular arrangements indicate that the observed Kondo resonance is independent on the molecular lattice. PMID- 17280448 TI - Robust transport properties in graphene. AB - Two-dimensional Dirac fermions are used to discuss quasiparticles in graphene in the presence of impurity scattering. Transport properties are completely dominated by diffusion. This may explain why recent experiments did not find weak localization in graphene. The diffusion coefficient of the quasiparticles decreases strongly with increasing strength of disorder. Using the Kubo formalism, however, we find a robust minimal conductivity that is independent of disorder. This is a consequence of the fact that the change of the diffusion coefficient is fully compensated by a change of the number of delocalized quasiparticle states. PMID- 17280447 TI - Electronic properties of graphene multilayers. AB - We study the effects of disorder in the electronic properties of graphene multilayers, with special focus on the bilayer and the infinite stack. At low energies and long wavelengths, the electronic self-energies and density of states exhibit behavior with divergences near half filling. As a consequence, the spectral functions and the conductivities acquire anomalous properties. In particular, we show that the quasiparticle decay rate has a minimum as a function of energy, there is a universal minimum value for the in-plane conductivity of order e(2)/h per plane and, unexpectedly, the c-axis conductivity is enhanced by disorder at low doping, leading to an enormous conductivity anisotropy at low temperatures. PMID- 17280449 TI - Inelastic effects in Aharonov-Bohm molecular interferometers. AB - Inelastic effects arising from electron-phonon coupling in molecular Aharonov Bohm (AB) interferometers are studied using the nonequilibrium Green's function method. Results for the magnetoconductance are compared for different values of the electron-phonon coupling strength. At low-bias voltages, the coupling to the phonons does not change the lifetime and leads mainly to scattering phase shifts of the conducting electrons. As a result of these dephasing processes, the magnetoconductance of the molecular AB interferometer becomes more sensitive to the threading magnetic flux as the electron-phonon coupling is increased, opposite to the behavior of an electric gate. PMID- 17280450 TI - Kondo quantum dots and the novel Kondo-doublet interaction. AB - We analyze the interactions between two Kondo quantum dots connected to a Rashba active quantum wire. We find that the Kondo-doublet interaction, at an interdot distance of the order of the wire Fermi length, is over an order of magnitude greater than the RKKY interaction. The effects induced on the Kondo-doublet interaction by the wire spin-orbit coupling can be used to control the quantum dots spin-spin correlation. These results imply that the widely used assumption that the RKKY is the dominant interaction between Anderson impurities must be revised. PMID- 17280451 TI - Encapsulation of floating carbon nanotubes in SiO(2). AB - In many applications of carbon nanotubes (CNT), it is desirable to have them embedded in a dielectric such as SiO(2), without significantly impacting their electronic properties. Here we investigate the CNT-SiO(2) interface of an embedded CNT using first-principles calculations. We show that strong Si-O-C bonds form, suggesting the feasibility of SiO(2) deposition on CNTs. We further show that subsequent hydrogenation eliminates all the Si-O-C bonds, leading to floating CNTs with electronic properties very close to those of pristine CNTs in vacuum. PMID- 17280452 TI - Nonlinear magnetoconductance of a classical ballistic system. AB - We study nonlinear transport through a classical ballistic system accounting for the Coulomb interaction between electrons. The joint effect of the applied bias V and magnetic field H on the electron trajectories results in a component of the nonlinear current I(V,H) which lacks the H-->-H symmetry: deltaI=alpha(cl)V(2)H. At zero temperature the magnitude of alpha(cl) is of the same order as that arising from the quantum interference mechanism. At higher temperatures the classical mechanism is expected to dominate due to its relatively weak temperature dependence. PMID- 17280453 TI - Disorder-enhanced dielectric response of nanoscale and mesoscopic insulators. AB - Enhancement of the dielectric response of insulators by disorder is theoretically proposed, where the quantum interference of electronic waves through the nanoscale or mesoscopic system and its change due to external perturbations control the polarization. In the disordered case with all the states being localized, the resonant tunneling, which is topologically protected, plays a crucial role, and enhances the dielectric response by a factor 30-40 compared with the pure case. The realization of this idea with accessible materials or structures is also discussed. PMID- 17280455 TI - Radiation from a single Josephson junction into free space due to Josephson oscillations. AB - We consider electromagnetic emission from a Josephson junction (JJ) in a resistive state in an external magnetic field and derive the radiation power from the dielectric layer inside a JJ directly into outside dielectric media. Matching the electric and magnetic fields at the JJ edges, we find dynamic boundary conditions for the phase difference in JJ. We find that the fraction of the power transformed into radiation is determined by the dissipation inside the JJ. It tends to unity as dissipation vanishes independently of the mismatch of the junction and dielectric media impedances. PMID- 17280454 TI - Strong coupling between localized plasmons and organic excitons in metal nanovoids. AB - Hybrid emitting exciton-plasmonic composites are constructed by coating arrays of spherical nanovoids embedded in a gold film with organic semiconducting molecular J-aggregate films. In such plasmonic crystals, localized plasmons confined inside the voids can be excited. We report the first observation of polaritonic spectral narrowing and strong coupling between localized plasmons and J-aggregate excitons with Rabi splittings of 230 meV at room temperature. PMID- 17280456 TI - Vortex line ordering in the driven three-dimensional vortex glass. AB - Resistively shunted junction dynamics is applied to the three-dimensional uniformly frustrated XY model with randomly perturbed couplings, as a model for driven steady states in a type-II superconductor with quenched point pinning. For a disorder strength p strong enough to produce a vortex glass in equilibrium, we map the phase diagram as a function of temperature T and uniform driving current I. Using finite size analysis and averaging over many realizations of quenched randomness we find a first-order melting T(m)(I) from a vortex line smectic to an anisotropic liquid. PMID- 17280457 TI - Angle-resolved photoemission study of the cobalt oxide superconductor Na(x)CoO(2) x yH(2)O: observation of the Fermi surface. AB - The cobalt oxide superconductor Na(x)CoO(2) x yH(2)O is studied by angle-resolved photoemission spectroscopy. We report the Fermi surface (FS) topology and electronic structure near the Fermi level (E(F)) in the normal state of Na(x)CoO(2) x yH(2)O. Our result indicates the presence of the hexagonal FS centered at the Gamma point, while the small pocket FSs along Gamma-K direction are absent, similar to Na(x)CoO(2). The top of the e(g)(') band, which is expected in band calculations to form the small pocket FSs, extends to within approximately 30 meV below E(F), closer to E(F) than in Na(x)CoO(2). We discuss its possible role in superconductivity, comparing with other experimental and theoretical results. PMID- 17280458 TI - Nonlinear coupling of nanomechanical resonators to josephson quantum circuits. AB - We propose a technique to couple the position operator of a nanomechanical resonator to a SQUID device by modulating its magnetic flux bias. By tuning the magnetic field properly, either linear or quadratic couplings can be realized, with a discretely adjustable coupling strength. This provides a way to realize coherent nonlinear effects in a nanomechanical resonator by coupling it to a Josephson quantum circuit. As an example, we show how squeezing of the nanomechanical resonator state can be realized with this technique. We also propose a simple method to measure the uncertainty in the position of the nanomechanical resonator without quantum state tomography. PMID- 17280459 TI - Conformal invariance and stochastic Loewner evolution processes in two dimensional Ising spin glasses. AB - We present numerical evidence that the techniques of conformal field theory might be applicable to two-dimensional Ising spin glasses with Gaussian bond distributions. It is shown that certain domain wall distributions in one geometry can be related to that in a second geometry by a conformal transformation. We also present direct evidence that the domain walls are stochastic Loewner (SLE) processes with kappa approximately 2.1. An argument is given that their fractal dimension d(f) is related to their interface energy exponent theta by d(f) - 1 = 3/[4(3 + theta)], which is consistent with the commonly quoted values d(f) approximately 1.27 and theta approximately -0.28. PMID- 17280460 TI - Spin Hamiltonian, competing small energy scales, and incommensurate long-range order in the highly frustrated Gd(3)Ga(5)O(12) garnet antiferromagnet. AB - Despite the availability of a spin Hamiltonian for the Gd(3)Ga(5)O(12) garnet (GGG) for over 25 years, there has so far been little theoretical insight regarding the many unusual low temperature properties of GGG. Here we investigate GGG in zero magnetic field using mean-field theory. We reproduce the spin liquid like correlations and, most importantly, explain the positions of the sharp peaks seen in powder neutron diffraction experiments. We show that it is crucial to treat accurately the long-range nature of the magnetic dipolar interactions to allow for a determination of the small exchange energy scales involved in the selection of the experimental ordering wave vector. Our results show that the incommensurate order in GGG is classical in nature, intrinsic to the microscopic spin Hamiltonian and not caused by weak disorder. PMID- 17280461 TI - Local spin moment distribution in antiferromagnetic molecular rings probed by NMR. AB - The NMR spectra of 19F and 53Cr have been obtained at low temperatures in a heterometallic substituted antiferromagnetic (AF) ring Cr7Cd with an S=3/2 ground state and compared with the spectra in a homometallic Cr8 AF ring with an S=0 ground state. From the analysis of the spectra one can derive directly model independent values of the staggered nonuniform distribution of the local moment in the heterometallic ring Cr7Cd. The experimental values are found to be in excellent agreement with the theoretical values calculated on the basis of an effective spin Hamiltonian which includes crystal field effects. PMID- 17280462 TI - Breakdown of hydrodynamic transport theory in the ordered phase of helimagnets. AB - It is shown that strong fluctuations preclude a hydrodynamic description of transport phenomena in helimagnets, such as MnSi, at T>0. This breakdown of hydrodynamics is analogous to the one in chiral liquid crystals. Mode-mode coupling effects lead to infinite renormalizations of various transport coefficients, and the actual macroscopic description is nonlocal. At T=0 these effects are weakened due to the fluctuation-dissipation theorem, and the renormalizations remain finite. Observable consequences of these results, as manifested in the neutron scattering cross section, are discussed. PMID- 17280463 TI - High-resolution Raman spectra with femtosecond pulses: an example of combined time- and frequency-domain spectroscopy. AB - Frequency-domain spectroscopy requires long pulses, whereas time-domain spectroscopy requires short pulses. This Letter demonstrates both theoretically and experimentally that simultaneous detection in frequency and time generates well-resolved spectra using intermediate-length pulses. In the case of coherent Raman spectroscopy, typical femtosecond pulses lie between the time and frequency domains. To demonstrate this method, a high-resolution Raman spectrum of nitrobenzene is obtained from 60 fs pulses. Phase control, pulse shaping, or pulses of widely differing duration are not required. PMID- 17280464 TI - Exchange and correlation effects in electronic excitations of Cu(2)O. AB - State-of-the-art theoretical methods fail in describing the optical absorption spectrum, band gap, and optical onset of Cu(2)O. We have extended a recently proposed self-consistent quasiparticle approach, based on the GW approximation, to the calculation of optical spectra, including excitonic effects. The band structure compares favorably with our present angle-resolved photoemission measurements. The excitonic effects based on these realistic band structure and screening provide a reliable optical absorption spectrum, which allows for a revised interpretation of its main structures. PMID- 17280465 TI - Magnetic and electric phase control in epitaxial EuTiO(3) from first principles. AB - We propose a design strategy--based on the coupling of spins, optical phonons, and strain--for systems in which magnetic (electric) phase control can be achieved by an applied electric (magnetic) field. Using first-principles density functional theory calculations, we present a realization of this strategy for the magnetic perovskite EuTiO(3). PMID- 17280466 TI - Atomistic simulations of a thermotropic biaxial liquid crystal. AB - We have performed molecular dynamics simulations of a 2,5-bis-(p-hydroxyphenyl) 1,3,4-oxadiazole mesogen (ODBP-Ph-C(7)) at a fully atomistic level for a range of temperatures within the region that has experimentally been assigned to a biaxial nematic phase. Analysis of the data shows that the simulated nematic phase is biaxial but that the degree of biaxiality is small. The simulations show also the formation of ferroelectric domains in the nematic where the molecular short axis is aligned with the oxadiazole dipoles parallel to each other. Removal of electrostatic interactions leads to destabilization of ferroelectric domains and destabilization of the biaxiality. An additional simulation shows the slow growth of a mesophase directly from the isotropic fluid over a period of approximately 50 ns. This is the first time this has been achieved within the framework of an all-atom model. PMID- 17280467 TI - Rheology of active filament solutions. AB - We study the viscoelasticity of an active solution of polar biofilaments and motor proteins. Using a molecular model, we derive the constitutive equations for the stress tensor in the isotropic phase and in phases with liquid crystalline order. The stress relaxation in the various phases is discussed. Contractile activity is responsible for a spectacular difference in the viscoelastic properties on opposite sides of the order-disorder transition. PMID- 17280468 TI - Comment on "Resonant inelastic X-ray scattering at the oxygen K resonance of NiO: nonlocal charge transfer and double-singlet excitations". PMID- 17280470 TI - Fighting filoviruses. PMID- 17280473 TI - Rotarix (RIX4414): an oral human rotavirus vaccine. AB - Rotavirus is the most common cause of severe gastroenteritis in children younger than 3 years of age worldwide. New rotavirus vaccine candidates were required to confer early protection against the most common rotavirus serotypes and to be well tolerated and not associated with intussusception. RIX4414 is a human attenuated G1(P8) oral rotavirus vaccine administered in two doses at approximately 6-24 weeks of age. The first dose may be administered from the age of 6 weeks. There should be an interval of at least 4 weeks between doses and the vaccination course should preferably be given before 16 weeks of age and must be completed, according to the manufacturer, by the age of 24 weeks. In a worldwide development program involving more than 70,000 children in six Phase I-III field trials, this vaccine proved to be nonreactogenic, well tolerated and not associated with intussusception. The vaccine provides over 85-96% protection against moderate-to-severe gastroenteritis caused by G1 and non-G1 serotypes, as demonstrated in Latin American and European clinical trial settings, respectively; and reduces gastroenteritis-related hospitalizations by more than 40% in Latin America and by 75% in European settings. PMID- 17280474 TI - Enhanced immune responses to an adenovirus CEA vaccine in CD4+CD25+ regulatory T cell inactivated mice. PMID- 17280475 TI - Allergen vaccine for moderate and severe allergic asthmatics. PMID- 17280476 TI - Should hepatitis B vaccine be used for infants? AB - Chronic hepatitis B virus infection causes nearly all the deaths from this virus. As the initial infection occurs without symptoms and decades prior to the onset of cirrhosis and liver cancer, these consequences are rarely recognized as being caused by the virus. Consequently, its public health importance is under recognized. Safe and effective vaccines have now been available for over 20 years. Concerns have been raised regarding the mercury preservative in vaccines leading to potential toxicity. But the evidence to date does not support any association of hepatitis B vaccine with serious adverse consequences. Protecting infants through immunization is the most effective control strategy. By 2005, over 80% of countries had implemented routine infant immunization. In countries with relatively low rates of hepatitis B virus infection, some have argued to defer immunization until later life. However, these arguments focus on the more visible acute infection. The possible future cost from a single infant infection argues for universal infant hepatitis B immunization--given the very high costs of treating its consequences (e.g., liver transplant) and the very low price of the vaccine. PMID- 17280477 TI - Mucosal vaccine development for botulinum intoxication. AB - Botulism has classically been considered to be a food- and water-borne disease. However, it was recently classified by the US National Institute of Allergy and Infectious Diseases (National Institute of Health) and the US Centers for Disease Control and Prevention as a Category A agent. Thus, the botulinum exotoxin, a neurotoxin, could be easily disseminated by bioterrorists through the air-borne route with a high morbidity and mortality rate. In this regard, a high priority should be given to the development of a safe and effective mucosal vaccine to protect against botulinum neurotoxins (BoNTs) since it is well known that the mucosal immune system is the first line of defense against major pathogens. Further, mucosal immunization has been shown to induce both mucosal and systemic immunity to pathogens. By contrast, the current injection-type vaccine only provides protective immunity in the systemic compartment. Clearly, the development of a safe and effective mucosal vaccine against this toxin should be a high priority. In this regard, it has been shown that both nasal and oral immunization approaches have been taken in order to protect from BoNT intoxication. In this article, we will discuss the importance of the development of a mucosal vaccine against botulinum and introduce current aspects of BoNT mucosal vaccines, which show that they effectively prevent mucosal BoNT intoxication. PMID- 17280478 TI - Acellular pertussis vaccines and the role of pertactin and fimbriae. AB - The introduction of acellular pertussis (Pa) vaccines in countries with a low uptake of whole-cell pertussis (Pw) vaccines has led to a dramatic reduction in pertussis disease. Diphtheria-tetanus-acellular pertussis (DTPa) vaccines have also ensured continued high level disease protection in these countries following the shift from Pw- to Pa-containing vaccines, and allowed pertussis booster programs to be implemented. Vaccines containing between one and five components have been licensed and implemented. Those with three or more components consisting of filamentous hemagglutinin (FHA), pertussis toxin (PT) and pertactin (PRN) are considered to be more effective than one/two-component Pa vaccines that contain only PT or both PT and FHA. Changes in circulating Bordetella pertussis strains may impact vaccine efficacy and, thus, incidence and transmission of pertussis and deserve to be followed carefully. To date, vaccine-induced shifts among fimbriae (FIM) are reported and this could impact the efficacy of FIM containing vaccines. Currently, FIM3 appears to be dominant in most European countries, Canada and Australia. Data obtained from a DTPa5 vaccine containing FIM2 and FIM3 have indicated a shift towards an increase in FIM3-expressing B. pertussis clinical breakthrough cases when compared with control vaccine. By contrast, relatively minor PT and PRN sequence polymorphisms have been identified without demonstrable association with vaccination programs. Adsorption of PRN to aluminum salt appears critical for optimal protective capacity in murine pertussis lung challenge. In addition, clinical studies have shown anti-PRN antibody levels to be higher when PRN is adsorbed at a 8-microg dosage versus non adsorbed PRN at a 3-microg dosage. The available data, therefore, demonstrate that appropriately formulated acellular vaccines containing PT and PRN are the preferred option for pertussis immunization. PMID- 17280479 TI - Development of vaccines for Marburg hemorrhagic fever. AB - Marburg (MARV) and Ebola viruses (EBOV) emerged from the rainforests of Central Africa more than 30 years ago causing outbreaks of severe and, usually, fatal hemorrhagic fever. EBOV has garnered the lion's share of the attention, fueled by the higher frequency of EBOV outbreaks, high mortality rates and importation into the USA, documented in such popular works as the best-selling novel 'The Hot Zone'. However, recent large outbreaks of hundreds of cases of MARV infection in the Democratic Republic of the Congo and Angola with case fatalities approaching 90% dramatically highlight its lethal potential. Although no vaccines or antiviral drugs for MARV are currently available, remarkable progress has been made over the last few years in developing potential countermeasures against MARV in nonhuman primate models. In particular, a vaccine based on attenuated recombinant vesicular stomatitis virus was recently shown to have both preventive and postexposure efficacy. PMID- 17280480 TI - Recent developments in mucosal vaccines against prion diseases. AB - Bovine spongiform encephalopathy in cattle is highly suspected to be orally transmitted to humans through contaminated food, causing new variant Creutzfeldt Jakob disease. However, no prophylactic procedures against these diseases, such as vaccines, in particular those stimulating mucosal protective immunity, have been established. The causative agents of these diseases, termed prions, consist of the host-encoded prion protein (PrP). Therefore, prions are immunologically tolerated, inducing no host antibody responses. This immune tolerance to PrP has hampered the development of vaccines against prions. We and others recently reported that the immune tolerance could be successfully broken and mucosal immunity could be stimulated by mucosal immunization of mice with PrP fused with bacterial enterotoxin or delivered using an attenuated Salmonella strain, eliciting significantly higher immunoglobulin A and G antibody responses against PrP. In this review, we will discuss these reports. PMID- 17280481 TI - Understanding orthopoxvirus interference with host immune responses to inform novel vaccine design. AB - Jenner's original vaccine used cowpox virus. Cowpox virus and, subsequently, vaccinia virus, a closely related Orthopoxvirus, provided the means to eradicate smallpox. This history and the unique properties of the virus suggest that vaccinia virus will continue to provide a useful vaccine platform. Yet, surprisingly, it has become apparent that much of the virus genome encodes accessory proteins that interfere with host immune responses to infection. Manipulation of these genes offers the potential for new generations of orthopoxvirus vaccines in which we will have far greater control over key features of the vaccination, including the sites of virus infection, the degree of virus replication, the pathogenicity of the virus and, most importantly, the suppression or induction of immune responses of specific types. PMID- 17280482 TI - Use of attenuated bacteria as delivery vectors for DNA vaccines. AB - Live, attenuated bacterial vaccines (LBV) are promising candidates for the induction of a broad-based immune response directed at recombinant heterologous antigens and the corresponding pathogen. LBVs allow vaccination through the mucosal surfaces and specific targeting of professional antigen-presenting cells located at the inductive sites of the immune system. A novel approach exploits attenuated intracellular bacteria as delivery vectors for eukaryotic antigen expression plasmids (so-called DNA vaccines). Candidate carrier bacteria include attenuated strains of Gram-positive and Gram-negative bacteria. These bacteria have been shown to deliver DNA vaccines to human cells in vitro and have also proven their in vivo efficacy in several experimental animal models of infectious diseases and different cancers. The clinical assessment of the safety, immunogenicity and efficacy of these candidate strains will be the next challenging step towards live bacterial DNA vaccines. PMID- 17280483 TI - Combination vaccines: synergistic simultaneous induction of antibody and T-cell immunity. AB - Vaccines have traditionally been designed to induce antibody responses and have been licensed on their capacity to induce high titers of circulating antibody to the pathogen. With our increased knowledge of host-pathogen interactions, it became apparent that induction of the cellular arm of the immune response is crucial to the efficacy of vaccines against intracellular pathogens and for providing appropriate help for antibody induction. Diverging strategies emerged that concentrate on developing candidate vaccines that solely induce either cellular or humoral responses. As most microbes reside at some point in the infectious cycle in the extracellular as well as intracellular space, and there is interplay between antibody and T cells, it is now apparent that both arms of immunity are essential to effectively control and eliminate the infection. It is, therefore, necessary to develop vaccines that can effectively induce a broad adaptive immune response. For vaccines targeted at diseases of the developing world, such as HIV, tuberculosis and malaria, it is imperative that these vaccines are simple to deliver and cost effective, that is,that optimum T-cell and antibody immunity is achieved with the minimum number of vaccinations. Combination vaccines, where an antibody-inducing subunit protein vaccine is coadministered with a T-cell-inducing poxvirus-based vaccine fulfill these requirements and induce sterile immunity to pathogen challenge. PMID- 17280484 TI - Redox control of calcium channels: from mechanisms to therapeutic opportunities. AB - Calcium plays an integral role in cellular function. It is a well-recognized second messenger necessary for signaling cellular responses, but in excessive amounts can be deleterious to function, causing cell death. The main route by which calcium enters the cytoplasm is either from the extracellular compartment or internal addistores via calcium channels. There is good evidence that calcium channels can respond to pharmacological compounds that reduce or oxidize thiol groups on the channel protein. In addition, reactive oxygen species such as hydrogen peroxide and superoxide that can mediate oxidative pathology also mediate changes in channel function via alterations of thiol groups. This review looks at the structure and function of calcium channels, the evidence that changes in cellular redox state mediate changes in channel function, and the role of redox modification of channels in disease processes. Understanding how redox modification of the channel protein alters channel structure and function is providing leads for the design of therapeutic interventions that target oxidative stress responses. PMID- 17280485 TI - Protection against myocardial ischemia-reperfusion injury by the angiogenic Masterswitch protein PR 39 gene therapy: the roles of HIF1alpha stabilization and FGFR1 signaling. AB - PR-39, a proline-arginine-rich angiogenic response peptide, has been implicated in myocardial ischemic reperfusion injury. The present study examined the cardioprotective abilities of PR39 gene therapy. Male C57Bl/J6 mice were randomized to intramyocardial injecton of 10(9) p.f.u. adenovirus encoding PR39 (PR39), FGFR1 dominant negative signaling construct (FGFR1-dn), empty vector (EV), or PR39 adenovirus plus 4 microg of plasmid endcoding a HIF1alpha dominant negative construct (PR39 + HIF1alpha-dn). Seven days later, hearts were subjected to 20 min of ischemia (I) and 2 h. reperfusion (R) ex vivo and aortic and coronary flow, left ventricular developed pressure (LVDP), and LVdp/dt were measured. Myocardial infarct (MI) size and cardiomyocyte apoptosis were measured by TTC staining and TUNEL, respectively. PR39 expression was robust up to 14 days after gene transfer and was absent after EV and FGFR1-dn. Hemodynamics showed no differences at baseline, and heart rate remained unchanged in all groups throughout the experiment. After I-R, hemodynamics remained unchanged in PR39 hearts, but deteriorated significantly in the other groups, except for aortic flow, which remained significantly higher in FGFR1-dn than in EV and PR39 + HIF1alpha-dn (p < 0.05), although it was lower than in PR39 (p < 0.05). MI was 8.7 +/- 0.9 % in PR39, 23.8 +/- 1.1% in FGFR1-dn, 29.9 +/- 2.2% in EV, and 30.8 +/- 2.7 % in PR39 + HIF1alpha-dn (PR39 vs. other groups: p < 0.05; FGFR1-dn vs. EV and PR39 + HIF1alpha-dn: p < 0.05). In PR39, HIF-1alpha protein was higher than in FGFR1-dn and EV. Importantly, cotransfection of HIF1alpha-dn with PR39 completely abolished cardioprotection by PR39. Cardioprotection by PR39 is likely conveyed by protective metabolic and survival responses through HIF1-alpha stabilization and not by angiogenesis, because baseline coronary flow was the same in all groups. Abrogation of FGFR1 signaling conveyed an intermediate degree of cardioprotection. PMID- 17280486 TI - Characterization of in vivo tissue redox status, oxygenation, and formation of reactive oxygen species in postischemic myocardium. AB - The current study aims to characterize the alterations of in vivo tissue redox status, oxygenation, formation of reactive oxygen species (ROS), and their effects on the postischemic heart. Mouse heart was subjected to 30 min LAD occlusion, followed by 60 min reperfusion. In vivo myocardial redox status and oxygenation were measured with electron paramagnetic resonance (EPR). In vivo tissue NAD(P)H and formation of ROS were monitored with fluorometry. Tissue glutathione/glutathione disulfide (GSH/GSSG) levels were detected with high performance liquid chromatography (HPLC). These experiments demonstrated that tissue reduction rate of nitroxide was increased 100% during ischemia and decreased 33% after reperfusion compared to the nonischemic tissue. There was an overshoot of tissue oxygenation after reperfusion. Tissue NAD(P)H levels were increased during and after ischemia. There was a burst formation of ROS at the beginning of reperfusion. Tissue GSH/GSSG level showed a 48% increase during ischemia and 29% decrease after reperfusion. In conclusion, the hypoxia during ischemia limited mitochondrial respiration and caused a shift of tissue redox status to a more reduced state. ROS generated at the beginning of reperfusion caused a shift of redox status to a more oxidized state, which may contribute to the postischemic myocardial injury. PMID- 17280487 TI - Seleno-L-methionine protects against beta-amyloid and iron/hydrogen peroxide mediated neuron death. AB - Increasing evidence suggests a role for oxidative stress in several neurodegenerative diseases, including Alzheimer's disease (AD), and that selenium compounds may function as antioxidants. To evaluate the antioxidant mechanism of selenium, primary rat hippocampal neurons were pretreated with seleno-L methionine (SeMet) for 16 h prior to treatment with iron/hydrogen peroxide (Fe(2+)/H(2)O(2)) or amyloid beta peptide (Abeta(2535)); free radical generation was assessed using laser confocal microscopy and CM-H(2)DCFDA and APF. Treatment with Fe(2+)/H(2)O(2) or Abeta significantly decreased cell survival and increased free radical generation compared to cultures treated with vehicle alone. In contrast, cultures pretreated with SeMet showed significantly (p < 0.05) increased survival and significantly lower CM-H(2)DCFDA and APF fluorescence compared to Fe(2+)/H(2)O(2) or Abeta treated cultures. To determine if SeMet protection was mediated by glutathione peroxidase (GPx), levels of GPx protein and activity were measured using confocal microscopy and a selenium-dependent GPx specific antibody and an activity assay. Pretreatment with SeMet significantly (p < 0.05) increased GPx protein and activity in Fe(2+)/H(2)O(2)- and Abeta-treated cultures compared to cultures treated with Fe(2+)/H(2)O(2) or Abeta alone. These data suggest that SeMet can decrease free radical generation induced by Fe(2+)/H(2)O(2) or Abeta through modulation of GPx and may be suitable as a potential therapeutic agent in neurodegenerative diseases where there is increased oxidative stress. PMID- 17280488 TI - Integrin-mediated cell adhesion and spreading engage different sources of reactive oxygen species. AB - The tightly regulated production of intracellular reactive oxygen species (ROS) participates in several biologic processes such as cellular growth, programmed cell death, senescence, and adhesion. It is increasingly evident that the same enzymatic processes that were originally linked to ROS generation during host defence or apoptosis execution are also involved in redox-mediated signal transduction. We investigated in murine NIH3T3 fibroblasts the contribution of a variety of redox-dependent events during signal transduction initiated by integrin engagement due to fibronectin stimulation and report that a mitochondrial ROS release occurs, strictly confined to the early phase of extracellular matrix (ECM) contact (10 min). Besides, 5-lipoxygenase (5-LOX) is engaged by integrin receptor ligation as another ROS source, contributing to the more-intense, second ROS burst (45 min), possibly orchestrating the spreading of cells in response to ECM contact. To define a potential mechanism for ROS signaling, we demonstrate that on integrin recruitment, the Src homology-2 domain containing phosphatase 2 (SHP-2) undergoes a reversible oxidization/inactivation to which mitochondrial and 5-lipoxygenase ROS contribute differentially. In keeping with a key role of oxidants during integrin signaling, the inactivation of SHP-2 prevents the dephosphorylation and inactivation of SHP-2 substrates (p125FAK and SHPS-1), thus enabling the continued propagation of the signal arising by integrin engagement. PMID- 17280489 TI - Spatial coordination of cell-adhesion molecules and redox cycling of iron in the microvascular inflammatory response to pulmonary injury. AB - Transmigration of phagocytic leukocytes (PLCs) from the peripheral blood into injured lung requires a conversion of the microvascular endothelial cells (ECs) to the proinflammatory phenotypes and spatiotemporal interplay of different types of cell adhesion molecules (CAMs) on PLC and endothelium. The present report is focused on involvement of iron-dependent redox signaling in spatial coordination of lung CAM due to either a pulmonary trauma or endotracheal iron administration in rats. Redox alterations, deposition of 3-nitrotyrosine, expression of VE cadherin, ICAM-1, and the PLC integrins, and the status of thioredoxin, Ref-1, NF kappaB and Nrf2 redox-sensitive elements in the alveolar microvasculature were assessed with EPR spectroscopy, immunobloting, and confocal microscopy. We demonstrated for the first time in vivo that the presence of catalytically active iron, deposition of myeloperoxidase, and induction of the oxidative stress in the lung-injury models were accompanied by (a) downregulation of VE-cadherin, (b) upregulation and polarization of ICAM-1 and the PLC integrins, and (c) nuclear translocation and interaction of thioredoxin, Ref-1, and NF-kappaB and complex structural changes in EC and PLC at the sites of their contacts. The studies suggested that a part of the proinflammatory action of iron in the lung resulted from its stimulation of the redox-sensitive factors. PMID- 17280490 TI - Alpha-lipoic Acid modulates heat shock factor-1 expression in streptozotocin induced diabetic rat kidney. AB - Increased oxidative stress and impaired heat shock protein (HSP) synthesis may contribute to diabetic nephropathy. The question of whether 8-week thiol antioxidant alpha-lipoic acid (LA) supplementation modulates HSP response and oxidative stress was studied in the kidney of streptozotocin-induced diabetic (SID) and nondiabetic rats. SID caused a histological mesangial expansion, tubular dilatation, and increased levels of transforming growth factor-beta (TGF beta), a mediator of glomerulosclerosis. SID increased 4-hydroxynonenal (4-HNE) protein adduct formation, a marker of lipid peroxidation, and heme oxygenase-1 (HO-1), also a marker of oxidative stress. Moreover, SID increased the DNA binding activity of heat shock factor-1 (HSF-1) and expression of heat shock protein 60 (HSP60). In contrast, LA supplementation partially reversed histological findings of glomerulosclerosis and decreased TGF-beta. LA also increased HSF-1 and decreased HO-1 protein expression, without affecting 4-HNE protein adduct levels. At the mRNA level, LA increased expression of HSF-1, HSP90, and glucose-regulated protein (GRP75) in both control and diabetic animals and HSP72 in SID rats. However, LA supplementation did not affect these HSPs at the protein level. These findings suggest that in addition to its antiglomerulosclerotic effects, LA can induce cytoprotective response in SID. PMID- 17280491 TI - Discordant response of glutathione and thioredoxin systems in human hypertension? AB - Hypertension is frequently associated with oxidative stress caused by high production of reactive oxygen species and compromised antioxidant defenses. Humans with essential hypertension, with or without treatment, and controls were examined (35 hypertensive and 30 normotensive). We noted a discordant response of the glutathione and thioredoxin systems in essential hypertension and to antihypertensive treatment. Further studies examining the significance of these thiols in hypertension outcomes are warranted. PMID- 17280492 TI - Adulteration of mustard cooking oil with argemone oil: do Indian food regulatory policies and antioxidant therapy both need revisitation? AB - Consumption of adulterated mustard oil (Brassica nigra) with argemone oil (Argemone mexicana) even for a short duration leads to a clinical condition referred as epidemic dropsy. In humans, argemone oil contained in adulterated mustard oil causes oxidative stress and death of red blood cells via met hemoglobin formation by altering pyridine nucleotide(s) and glutathione redox potential. Argemone oil contamination poses a serious threat to human health and should be checked by appropriate regulatory measures. Antioxidant therapy provides symptomatic relief and should be seriously considered for therapeutic interventions against argemone oil toxicity. PMID- 17280493 TI - Does s-methyl methanethiosulfonate trap the thiol-disulfide state of proteins? AB - S-Methyl methanethiosulfonate (MMTS) is a reagent used to trap the natural thiol disulfide state of the proteins. The efficiency of trapping mixed disulfides in vivo has been found to be higher for MMTS than for the more commonly used N ethylmaleimide. MMTS has also been used for studying protein S-nitrosylation and the role of catalytic and structural cysteines on enzyme activities. However, the treatment of a protein with MMTS can potentially generate additional protein disulfide bonds. These results indicate that in vitro MMTS is able to form both intramolecular and intermolecular protein disulfide bonds in addition to dithiomethane adducts. PMID- 17280494 TI - Future roles for FoxM1 inhibitors in cancer treatments. PMID- 17280495 TI - Neoadjuvant chemotherapy for bladder transitional cell carcinoma: a new standard of care? PMID- 17280496 TI - Expanding the indications for sentinel lymph node surgery in breast cancer. PMID- 17280498 TI - AMD3100: CXCR4 antagonist and rapid stem cell-mobilizing agent. AB - As hematopoietic stem cells collected from peripheral blood are increasingly used for autologous and allogeneic stem cell transplantation, new approaches for the mobilization of stem cells are needed. These should have the goal of improving stem cell collection and reducing the duration and toxicity of the mobilization process. AMD3100, a specific inhibitor of CXCR4, one of the key molecules that tethers hematopoietic stem cells to the bone marrow microenvironment, is a promising new agent currently in clinical development for autologous and allogeneic stem cell mobilization. Early clinical trials have demonstrated that AMD3100 rapidly mobilizes stem cells to the peripheral blood, with minimal side effects. In Phase II trials, mobilization with the combination of AMD3100 and granulocyte colony-stimulating factor (G-CSF) results in the collection of more progenitor cells than G-CSF alone. PMID- 17280499 TI - Alemtuzumab in chronic lymphocytic leukemia. AB - Alemtuzumab is a humanized monoclonal antibody specific for CD52, a glycosylphosphatidylinositol-anchored, lymphocyte-surface glycoprotein. Administration of alemtuzumab to patients with chronic lymphocytic leukemia depletes normal and neoplastic lymphocytes from the blood, spleen and marrow, but appears to be less effective in resolving lymphadenopathy. Owing to its activity in clearing leukemia cells of patients who are refractory to purine analogs, such as fludarabine, alemtuzumab became the first and only monoclonal antibody approved by the US FDA and other regulatory authorities for the treatment of chronic lymphocytic leukemia. Here we review the results of clinical studies evaluating the activity and safety of alemtuzumab when used alone or in combination with other antileukemia agents for the treatment of this disease. PMID- 17280500 TI - Intensity-modulated radiotherapy for the treatment of pelvic lymph nodes in prostate cancer. AB - Evaluation of: Wang-Chesebro A, Xia P, Coleman J, Akazawa C, Roach M 3rd: Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with 3D conformal radiation therapy in clinically localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 66, 654-662 (2006). A large randomized Phase III trial (RTOG 94-13) demonstrated improved progression free survival for the irradiation of the pelvic lymphatics compared with treatment of the prostate only in patients with a high risk of lymph node involvement. Recent studies have indicated that the conventional target volume might miss substantial parts of the lymphatic drainage of the prostate. This retrospective planning study compared conventional, 3D-conformal and intensity modulated radiotherapy (IMRT) for the treatment of pelvic lymph nodes. Field shaping based on bony landmarks was shown to result in inadequate target coverage compared with 3D-conformal and IMRT planning. Regarding sparing of rectum, bladder, small bowl and penile bulb, the IMRT plans were highly superior. In summary, IMRT may result in increased rates of regional control with simultaneously decreased rates of toxicity. Integration of functional imaging into treatment planning and image guidance during treatment is expected to further improve the therapeutic ratio. PMID- 17280501 TI - Histochemical, immunohistochemical and cytogenetic markers in salivary gland tumor pathology. AB - Evaluation of: Adeyemi BF, Kolude BM, Akang EE, Lawoyin JO: A study of silver nucleolar organizer regions in categorization and prognosis of salivary gland tumors. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 102, 513-520 (2006). In this study, various confirmed benign and malignant salivary gland tumors underwent a known histochemical silver staining method involving nuclear associated proteins with diagnostic and prognostic capacity in other malignant tumors. The study examined the methods' ability to differentiate between benign and malignant salivary gland tumors and between different histopathological grades of malignant tumors, and sought correlations between the staining results and staging, metastatic disease and survival. The staining method proved inadequate, confirming many previously published results. This article highlights the growing awareness of pathologists and oral pathologists in developing countries to the uniqueness of salivary gland tumors, and demonstrates their understanding of the importance of both early detection and appropriate treatment. PMID- 17280502 TI - Gene-expression analysis and the basal-like breast cancer subtype. AB - Analysis of the patterns of gene expression in breast cancer suggests that it is not a single entity, but is comprised of several biologically distinct subtypes with characteristic molecular profiles. These molecular profiles confirm the clinical impression that estrogen receptor (ER)-negative differs from ER positive, and expands our understanding by identifying breast cancer subtypes, including the basal-like and human epidermal growth factor receptor (HER)2/ER subtypes within the ER-negative subset, and the luminal A and B subtypes within ER-positive disease. The basal-like subtype is characterized by the low expression levels of the ER-related and the HER2-related group of genes, and therefore is often 'triple negative' on clinical assays for these proteins. This review discusses the molecular profiles of breast cancer with a focus on the clinical characteristics of, and treatment options for, the basal-like subtype. PMID- 17280503 TI - Positive and negative aspects of sentinel lymph node biopsy in breast cancer. AB - The sentinel lymph node (SLN) is the first lymph node to receive lymphatic drainage from a tumor. SLN biopsy has become a mainstay of breast cancer management and is used when the axilla is clinically clear of disease. Staging of the axilla in breast cancer is used to predict prognosis and in planning adjuvant treatment. SLN biopsy is not used where there has been previous axillary or breast radiotherapy or surgery, locally advanced or inflammatory disease and stage IV disease. Controversies remain in several specific clinical situations, including management of the axilla following detection of a positive SLN. There are no sufficiently robust predictive tumor features to prevent completion axillary dissection in these cases. However, there is evidence that immediate axillary surgery for operable, clinically node-negative breast cancer provides no survival benefit and may be unnecessary for many women. SLN biopsy may have a role after neoadjuvant chemotherapy, sparing some women from axillary node dissection. Further work is required to ascertain SLN biopsy sensitivity prior to its routine use in the clinic for multicentric and multifocal disease. PMID- 17280504 TI - Radioembolization with Yttrium-90 microspheres: review of an emerging treatment for liver tumors. AB - Understanding the effect of radiation on tissue, the principles of dosimetry and fractionation have led to the acceptance and adoption of radiation as a standard treatment option for cancer. Delivered in staged and scheduled aliquots, radiation will break nucleic strands and cause cellular death. In general, radiation therapies are delivered using external techniques (external beam and intensity-modulated therapy). One of the limitations of such external techniques is that of nontarget radiation. That is, despite best efforts to collimate and reflect radiation beams to a small target, nontarget radiation and a dose to areas outside the tumor remains a distinct possibility. With the advent of radioembolization using Yttrium-90 microspheres (90Y), the radiation source is delivered optimally through a novel mechanism: directly into the blood vessel providing flow to the tumor. This revolutionary approach capitalizes on the basic principles of tumor hypervascularity, concentrating radiation within that tumor, while at the same time minimizing the risks of nontarget radiation. This review elaborates on this technology. PMID- 17280505 TI - Clinical significance of the p53 pathway and associated gene therapy in non-small cell lung cancers. AB - Many molecules, including several regulators and various target genes, are involved in the biological functions of p53, thus making the p53 pathway rather complicated. However, recent clinical studies have demonstrated that most human cancers have an abnormality in some of the molecules associated with the p53 pathway. Most non-small cell lung cancers (NSCLCs) have either mutations of p53, a reduced p14 alternate reading frame expression, a reduced herpesvirus associated ubiquitin-specific protease expression or a reduced p33 inhibitor of growth gene1b expression. As a result, the balance of expression of p53 target genes, such as p21, Bax and PUMA, regulates the biological behavior and determines the fate of tumor cells. To date, many studies on cancer gene therapy using these molecules associated with the p53 pathway have been performed to develop new strategies for treating NSCLC patients. Thus, the establishment of a comprehensive and simple evaluation protocol for the p53 pathway is required for clinical use. PMID- 17280506 TI - Resection versus radiosurgery for patients with brain metastases. AB - Brain metastases occur in 20-40% of adult cancer patients and the incidence is apparently increasing. Despite advances in treatment, the prognosis of these patients is poor, with a median survival of approximately 4 months. Whole brain radiation therapy is the standard of care for most patients with brain metastases. Randomized trials have demonstrated that focal treatments, such as resection and radiosurgery, yield significant improvement in the survival of patients with a single metastasis. The utility of these strategies, specifically in terms of increased survival, is unclear in patients with more than one metastasis. In addition to focal treatments, future directions in the treatment of brain metastases include the development of intraoperative imaging capabilities, improved methods of identifying patients who are likely to benefit from treatment, systemic agents, such as chemotherapy and radiosensitizers, and the incorporation of targeted and antiangiogenic therapies. PMID- 17280507 TI - State-of-the-art radiotherapy in the management of clinically localized prostate carcinoma. AB - Four Phase III trials demonstrating higher prostate-specific antigen control rates in prostate cancer patients treated with higher doses of radiation have changed the standard of care. Emerging on-line technologies, improved imaging and computer algorithms, combined with an improved understanding of how best to apply them, have allowed radiation oncologists to move ever closer to the optimal application of curative radiation. This technology allows a higher dose to be delivered to tumor-bearing areas while minimizing the dose delivered to surrounding normal tissues. Real-time adaptive techniques have made each step more accurate, and commercialization has increasingly moved these advances further into the community setting. Phase III trials have also helped to define the role of hormonal therapy in combination with radiation and the benefits of prophylactic pelvic nodal radiotherapy in subsets of patients. We have also learnt how to optimize the use of prostate-specific antigen to better determine success and failure following radiotherapy. PMID- 17280508 TI - A topographical study on the event-related potential correlates of scrambled word order in Japanese complex sentences. AB - One of the most fundamental and universal properties of human language is a phenomenon called displacement. In the present study, we used multichannel event related potentials (ERPs) to identify the nature of this phenomenon with Japanese, a subject-object-verb (SOV) language of relatively free word order. The ERPs of sentences of canonical word order (CC) were compared with those of non canonical word order in two types of Japanese complex sentences; namely, in those which can be described as being in a middle-scrambled condition (MSC) and in those in a long-scrambled condition (LSC). The sustained anterior negativity (SAN) and the P600 in the pregap position were observed in the LSC, compared to the CC, and they are consistent with previous findings. The SAN, exhibiting a tripartite nature in morphology and scalp distribution, mainly reflected a storage cost of scrambled elements in sentence comprehension. The subsequent P600 had a left fronto-temporal maximum, distinguished from a posterior P600, taken as a reflector of the thematic role assignment in previous related studies. It is argued that the P600 in the present study reflects a cost of structural integration intensively depending on the case marker information. A compositional interpretation of sentence meanings was also observed, reflected in an anterior negativity at the postgap verbal position, which cannot be differentiated at the pregap verbal position in the languages of subject-verb-object (SVO) word order. PMID- 17280509 TI - Correlates of stimulus-response congruence in the posterior parietal cortex. AB - Primate behavior is flexible: The response to a stimulus often depends on the task in which it occurs. Here we study how single neurons in the posterior parietal cortex (PPC) respond to stimuli which are associated with different responses in different tasks. Two rhesus monkeys performed a task-switching paradigm. Each trial started with a task cue instructing which of two tasks to perform, followed by a stimulus requiring a left or right button press. For half the stimuli, the associated responses were different in the two tasks, meaning that the task context was necessary to disambiguate the incongruent stimuli. The other half of stimuli required the same response irrespective of task context (congruent). Using this paradigm, we previously showed that behavioral responses to incongruent stimuli are significantly slower than to congruent stimuli. We now demonstrate a neural correlate in the PPC of the additional processing time required for incongruent stimuli. Furthermore, we previously found that 29% of parietal neurons encode the task being performed (task-selective cells). We now report differences in neuronal timing related to congruency in task-selective versus task nonselective cells. These differences in timing suggest that the activity in task nonselective cells reflects a motor command, whereas activity in task-selective cells reflects a decision process. PMID- 17280510 TI - Intermanual Differences in movement-related interhemispheric inhibition. AB - Interhemispheric inhibition (IHI) between motor cortical areas is thought to play a critical role in motor control and could influence manual dexterity. The purpose of this study was to investigate IHI preceding movements of the dominant and nondominant hands of healthy volunteers. Movement-related IHI was studied by means of a double-pulse transcranial magnetic stimulation protocol in right handed individuals in a simple reaction time paradigm. IHI targeting the motor cortex contralateral (IHI(c)) and ipsilateral (IHI(i)) to each moving finger was determined. IHI(c) was comparable after the go signal, a long time preceding movement onset, in both hands. Closer to movement onset, IHI(c) reversed into facilitation for the right dominant hand but remained inhibitory for left nondominant hand movements. IHI(i) displayed a nearly constant inhibition with a trough early in the premovement period in both hands. In conclusion, our results unveil a more important modulation of interhemispheric interactions during generation of dominant than nondominant hand movements. This modulation essentially consisted of a shift from a balanced IHI at rest to an IHI predominantly directed toward the ipsilateral primary motor cortex at movement onset. Such a mechanism might release muscles from inhibition in the contralateral primary motor cortex while preventing the occurrence of the mirror activity in ipsilateral primary motor cortex and could therefore contribute to intermanual differences in dexterity. PMID- 17280511 TI - Developmental differences in sleep's role for implicit off-line learning: comparing children with adults. AB - Sleep crucially contributes to the off-line consolidation of memories. Although this view was confirmed in numerous studies in adults, it is not known whether it can be generalized to sleep during development. Here, we examined effects of sleep on implicit memory formation considered of particular relevance in children, because brain structures underlying implicit learning develop earlier in ontogeny than structures supporting explicit learning. Subjects were 7- to 11 year-old children (n = 14) and 20- to 30-year-old adults (n = 12) tested on a serial reaction time task before (learning) and after (retest) equal length retention periods of overnight sleep and daytime wakefulness. At learning, after eight training blocks, all subjects had acquired implicit knowledge of the probabilistic rules underlying the sequential stimulus materials, as indicated by a substantial difference in response time to grammatical versus nongrammatical trials in two test blocks that followed the training blocks. At learning, this response time difference was greater in children (48.49 +/- 6.08 msec) than adults (28.02 +/- 3.65 msec, p < .01), but did not differ between sleep and wake retention conditions in either age group. Consistent with previous studies, retesting in the adults revealed that the reaction time differences between grammatical and nongrammatical trials increased by 9.78 +/- 4.82 msec after sleep, but decreased by -12.76 +/- 5.49 msec after the wake retention period (p < .01). Contrary to this finding in adults, sleep in children did not lead to an increase, but to a decrease in the reaction time difference averaging -26.68 +/- 12.25 msec (p < .05), whereas across the wake retention interval the reaction time difference remained nearly unchanged. The sleep-dependent deterioration in measures of implicit sequence knowledge in children was in striking contrast to the gain of such knowledge in the adults during sleep (p < .01). Our findings indicate that the functional role of sleep in implicit memory consolidation depends on age. We speculate that the overnight decrease of implicit knowledge in children reflects a preferential effect of sleep toward the enhancement of explicit aspects of task performance that interferes with implicit performance gains. PMID- 17280512 TI - Who are you talking about? Tracking discourse-level referential processing with event-related brain potentials. AB - In this event-related brain potentials (ERPs) study, we explored the possibility to selectively track referential ambiguity during spoken discourse comprehension. Earlier ERP research has shown that referentially ambiguous nouns (e.g., "the girl" in a two-girl context) elicit a frontal, sustained negative shift relative to unambiguous control words. In the current study, we examined whether this ERP effect reflects "deep" situation model ambiguity or "superficial" textbase ambiguity. We contrasted these different interpretations by investigating whether a discourse-level semantic manipulation that prevents referential ambiguity also averts the elicitation of a referentially induced ERP effect. We compared ERPs elicited by nouns that were referentially nonambiguous but were associated with two discourse entities (e.g., "the girl" with two girls introduced in the context, but one of which has died or left the scene), with referentially ambiguous and nonambiguous control words. Although temporally referentially ambiguous nouns elicited a frontal negative shift compared to control words, the "double bound" but referentially nonambiguous nouns did not. These results suggest that it is possible to selectively track referential ambiguity with ERPs at the level that is most relevant to discourse comprehension, the situation model. PMID- 17280513 TI - Individual differences in amygdala and ventromedial prefrontal cortex activity are associated with evaluation speed and psychological well-being. AB - Using functional magnetic resonance imaging, we examined whether individual differences in amygdala activation in response to negative relative to neutral information are related to differences in the speed with which such information is evaluated, the extent to which such differences are associated with medial prefrontal cortex function, and their relationship with measures of trait anxiety and psychological well-being (PWB). Results indicated that faster judgments of negative relative to neutral information were associated with increased left and right amygdala activation. In the prefrontal cortex, faster judgment time was associated with relative decreased activation in a cluster in the ventral anterior cingulate cortex (ACC, BA 24). Furthermore, people who were slower to evaluate negative versus neutral information reported higher PWB. Importantly, higher PWB was strongly associated with increased activation in the ventral ACC for negative relative to neutral information. Individual differences in trait anxiety did not predict variation in judgment time or in amygdala or ventral ACC activity. These findings suggest that people high in PWB effectively recruit the ventral ACC when confronted with potentially aversive stimuli, manifest reduced activity in subcortical regions such as the amygdala, and appraise such information as less salient as reflected in slower evaluative speed. PMID- 17280514 TI - Dissociation between striatal regions while learning to categorize via feedback and via observation. AB - Convergent evidence from functional imaging and from neuropsychological studies of basal ganglia disorders indicates that the striatum is involved in learning to categorize visual stimuli with feedback. However, it is unclear which cognitive process or processes involved in categorization is or are responsible for striatal recruitment; different regions of the striatum have been linked to feedback processing and to acquisition of stimulus-category associations. We examined the effect of the presence of feedback during learning on striatal recruitment by comparing feedback learning with observational learning of an information integration task. In the feedback task, participants were shown a stimulus, made a button press response, and then received feedback as to whether they had made the correct response. In the observational task, participants were given the category label before the stimulus appeared and then made a button press indicating the correct category membership. A region-of-interest analysis was used to examine activity in three regions of the striatum: the head of the caudate, body and tail of the caudate, and the putamen. Activity in the left head of the caudate was modulated by the presence of feedback: The magnitude of activation change was greater during feedback learning than during observational learning. In contrast, the bilateral body and tail of the caudate and the putamen were active to a similar degree in both feedback and observational learning. This pattern of results supports a functional dissociation between regions of the striatum, such that the head of the caudate is involved in feedback processing, whereas the body and tail of the caudate and the putamen are involved in learning stimulus-category associations. The hippocampus was active bilaterally during both feedback and observational learning, indicating potential parallel involvement with the striatum in information integration category learning. PMID- 17280515 TI - Maintenance of visual stability in the human posterior parietal cortex. AB - Visual stability refers to our stable visuospatial perceptions despite the unstable visual input caused by saccades. Functional neuroimaging results, studies on patients with posterior parietal cortex (PPC) lesions, and single-unit recordings in the lateral intraparietal sulcus of primates indirectly suggest that the PPC might be a potential locus of visual stability through its involvement with spatial remapping. Here we directly explored the role of the PPC in visual stability by applying transcranial magnetic stimulation (TMS) while participants performed a perisaccadic displacement detection task. We show that TMS over the PPC but not a frontal control site alters sensitivity to displacement detection when administered just before contralateral saccades and that a general impairment in attention or in the perception of apparent motion cannot account for the decreased sensitivity. The specific relationship between the timing of TMS and saccade direction demonstrates that saccadic suppression of displacement (SSD) is likely a consequence of noisy contralateral spatial representations in the PPC around the time of a saccade. The same mechanism may keep the unstable visual world in the temporal proximity of saccades from reaching our consciousness. PMID- 17280516 TI - The regulation of cognitive control following rostral anterior cingulate cortex lesion in humans. AB - The contribution of the medial prefrontal cortex, particularly the anterior cingulate cortex (ACC), to cognitive control remains controversial. Here, we examined whether the rostral ACC is necessary for reactive adjustments in cognitive control following the occurrence of response conflict [Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. Conflict monitoring and cognitive control. Psychological Review, 108, 624-652, 2001]. To this end, we assessed 8 patients with focal lesions involving the rostral sector of the ACC (rACC patients), 6 patients with lesions outside the frontal cortex (non-FC patients), and 11 healthy subjects on a variant of the Simon task in which levels of conflict were manipulated on a trial-by-trial basis. More specifically, we compared Simon effects (i.e., the difference in performance between congruent and incongruent trials) on trials that were preceded by high conflict (i.e., incongruent) trials with those on trials that were preceded by low-conflict (i.e., congruent) trials. Normal controls and non-FC patients showed a reduction of the Simon effect when the preceding trial was incongruent, suggestive of an increase in cognitive control in response to the occurrence of response conflict. In contrast, rACC patients attained comparable Simon effects following congruent and incongruent events, indicating a failure to modulate their performance depending on the conflict level generated by the preceding trial. Furthermore, damage to the rostral ACC impaired the posterror slowing, a further behavioral phenomenon indicating reactive adjustments in cognitive control. These results provide insights into the functional organization of the medial prefrontal cortex in humans and its role in the dynamic regulation of cognitive control. PMID- 17280517 TI - Deceiving others: distinct neural responses of the prefrontal cortex and amygdala in simple fabrication and deception with social interactions. AB - Brain mechanisms for telling lies have been investigated recently using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. Although the advent of these techniques has gradually enabled clarification of the functional contributions of the prefrontal cortex in deception with respect to executive function, the specific roles of subregions within the prefrontal cortex and other brain regions responsible for emotional regulation or social interactions during deception are still unclear. Assuming that the processes of falsifying truthful responses and deceiving others are differentially associated with the activities of these regions, we conducted a positron emission tomography experiment with 2 (truth, lie) x 2 (honesty, dishonesty) factorial design. The main effect of falsifying the truthful responses revealed increased brain activity of the left dorsolateral and right anterior prefrontal cortices, supporting the interpretation of previous studies that executive functions are related to making untruthful responses. The main effect of deceiving the interrogator showed activations of the ventromedial prefrontal (medial orbitofrontal) cortex and amygdala, adding new evidence that the brain regions assumed to be responsible for emotional processing or social interaction are active during deceptive behavior similar to that in real-life situations. Further analysis revealed that activity of the right anterior prefrontal cortex showed both effects of deception, indicating that this region has a pivotal role in telling lies. Our results provide clear evidence of functionally dissociable roles of the prefrontal subregions and amygdala for human deception. PMID- 17280518 TI - A review of functional imaging studies on category specificity. AB - A review of 20 functional imaging studies that compared visual processing of natural objects and artifacts in normal subjects is presented. The studies included fulfilled three criteria: (i) they used pictures as stimuli, (ii) they were based on direct contrasts between categories, and (iii) they reported findings in Talairach space. Not a single area is consistently activated for a given category across all studies. In contrast, 11 out of 29 regions are reported activated by both artifacts and natural objects. It is argued that the inconsistency is unlikely to reflect differences between studies in task requirements alone. Rather, the most likely causes of the inconsistency are: (i) adoption of liberal statistical thresholds that may yield false-positive activations, (ii) limited sensitivity due to few observations, and (iii) failure to match categories on confounding variables such as familiarity and visual complexity. Of the most consistent activations found, none appear to be selective for natural objects or artifacts. The findings reviewed are compatible with theories of category specificity that assume a widely distributed conceptual system not organized by category. PMID- 17280519 TI - Attention and sensory interactions within the occipital cortex in the early blind: an fMRI study. AB - Visual deprivation early in life results in occipital cortical responsiveness across a broad range of perceptual and cognitive tasks. In the reorganized occipital cortex of early blind (EB) individuals, the relative lack of specificity for particular sensory stimuli and tasks suggests that attention effects may play a prominent role in these areas. We wished to establish whether occipital cortical areas in the EB were responsive to stimuli across sensory modalities (auditory, tactile) and whether these areas maintained or altered their activity as a function of selective attention. Using a three-stimulus oddball paradigm and event-related functional magnetic resonance imaging, auditory and tactile tasks presented separately demonstrated that several occipital regions of interest (ROIs) in the EB, but not sighted controls (SCs), responded to targets and task-irrelevant distracter stimuli of both modalities. When auditory and tactile stimuli were presented simultaneously with subjects alternating attention between sensory streams, only the calcarine sulcus continued to respond to stimuli in both modalities. In all other ROIs, responses to auditory targets were as large or larger than those observed in the auditory alone condition, but responses to tactile targets were attenuated or abolished by the presence of unattended auditory stimuli. Both auditory and somatosensory cortices responded consistently to auditory and tactile targets, respectively. These results reveal mechanisms of orienting and selective attention within the visual cortex of EB individuals and suggest that mechanisms of enhancement and suppression interact asymmetrically on auditory and tactile streams during bimodal sensory presentation. PMID- 17280520 TI - Activity in the visual cortex is modulated by top-down attention locked to reaction time. AB - We studied the correlation between perception and hemodynamic activity in the visual cortex in a change detection task. Whenever the observer perceived the location of a change, rightly or wrongly, the blood oxygenation level-dependent signal increased in the primary visual cortex and the nearby extrastriate areas above the baseline activity caused by the visual stimulation. This non-sensory evoked activity was localized and corresponded to the perceived location of the change. When a change was missed, or when observers attended to a different task, the change failed to evoke such a response. The latency of the nonsensory component increased linearly with subjects' reaction time, with a slope of one, and its amplitude was independent of contrast. Control experiments are compatible with the hypothesis that the nonsensory hemodynamic signal is mediated by top down spatial attention, linked to (but separate from) awareness of the change. PMID- 17280521 TI - Enhancing visuomotor adaptation by reducing error signals: single-step (aware) versus multiple-step (unaware) exposure to wedge prisms. AB - Neglect patients exhibit both a lack of awareness for the spatial distortions imposed during visuomanual prism adaptation procedures, and exaggerated postadaptation negative after-effects. To better understand this unexpected adaptive capacity in brain-lesioned patients, we investigated the contribution of awareness for the optical shift to the development of prism adaptation. The lack of awareness found in neglect was simulated in a multiple-step group where healthy subjects remained unaware of the optical deviation because of its progressive stepwise increase from 2 degrees to 10 degrees . We contrasted this method with the classical single-step group in which subjects were aware of the visual shift because they were directly exposed to the full 10 degrees shift. Because the number of pointing trials was identical in the two groups, the total amount of deviation exposure was 50% larger in the single-step group. Negative after-effects were examined with an open-loop pointing task performed with the adapted hand, and generalization was tested with open-loop pointing with the nonexposed hand to visual and auditory targets. The robustness of adaptation was assessed by an open-loop pointing task after a simple de-adaptation procedure. The progressive, unaware condition was associated with larger negative after effects, transfer to the non-exposed hand for the visual and auditory pointing tasks, and greater robustness. The amount of adaptation obtained remained, nevertheless, lower than the exaggerated adaptive capacity seen in patients with neglect. Implications for the functional mechanisms and the anatomical substrates of prism adaptation are discussed. PMID- 17280522 TI - Modulation of memory formation by stimulus content: specific role of the medial prefrontal cortex in the successful encoding of social pictures. AB - It is unclear whether the involvement of the medial prefrontal cortex (mPFC) during encoding is restricted to the evaluative processing of to-be-encoded stimuli or if it is instead actively engaged during memory formation. The difficulty of assessing the contribution of the mPFC to encoding based on previous neuroimaging studies partly arises from the use of several types of stimuli, such as emotional or social ones. These different types of stimulus content could differently modulate mPFC activity during memory formation and thus partly explain the variable contribution of this region to encoding. Using emotional/neutral and social/nonsocial pictures, we conducted an event-related functional magnetic resonance imaging study using a subsequent memory paradigm as the main analytical strategy. We observed that the brain activity in the dorsal and orbital mPFC is significantly and specifically predictive of the successful encoding of social compared with nonsocial pictures. In contrast, the activity in the amygdala specifically predicts the successful encoding of emotional compared with neutral pictures. The modulation of the mPFC by social information in a memory encoding context could be associated with the initiation of self referential processes whose contribution is to enhance memory formation. PMID- 17280523 TI - Anatomical and physiological plasticity of dendritic spines. AB - In excitatory neurons, most glutamatergic synapses are made on the heads of dendritic spines, each of which houses the postsynaptic terminal of a single glutamatergic synapse. We review recent studies demonstrating in vivo that spines are motile and plastic structures whose morphology and lifespan are influenced, even in adult animals, by changes in sensory input. However, most spines that appear in adult animals are transient, and the addition of stable spines and synapses is rare. In vitro studies have shown that patterns of neuronal activity known to induce synaptic plasticity can also trigger changes in spine morphology. Therefore, it is tempting to speculate that the plastic changes of spine morphology reflect the dynamic state of its associated synapse and are responsible to some extent for neuronal circuitry remodeling. Nevertheless, morphological changes are not required for all forms of synaptic plasticity, and whether changes in the spine shape and size significantly impact synaptic signals is unclear. PMID- 17280524 TI - Populus: a model system for plant biology. AB - With the completion of the Populus trichocarpa genome sequence and the development of various genetic, genomic, and biochemical tools, Populus now offers many possibilities to study questions that cannot be as easily addressed in Arabidopsis and rice, the two prime model systems of plant biology and genomics. Tree-specific traits such as wood formation, long-term perennial growth, and seasonality are obvious areas of research, but research in other areas such as control of flowering, biotic interactions, and evolution of adaptive traits is enriched by adding a tree to the suite of model systems. Furthermore, the reproductive biology of Populus (a dioeceous wind-pollinated long-lived tree) offers both new possibilities and challenges in the study and analysis of natural genetic and phenotypic variation. The relatively close phylogenetic relationship of Populus to Arabidopsis in the Eurosid clade of Eudicotyledonous plants aids in comparative functional studies and comparative genomics, and has the potential to greatly facilitate studies on genome and gene family evolution in eudicots. PMID- 17280526 TI - Association of the VDR translation start site polymorphism and fracture risk in older women. AB - We evaluated the association between the VDR translation start site polymorphism and osteoporotic phenotypes among 6698 older white women. Women with the C/C genotype had lower wrist BMD and an increased risk of wrist and all non-spine/low trauma fractures. The high frequency of this variant confers a population attributable risk that is similar to several established risk factors for fracture. INTRODUCTION: The vitamin D receptor (VDR) is a nuclear receptor that regulates bone formation, bone resorption, and calcium homeostasis. A common C to T polymorphism in exon 2 of the VDR gene introduces a new translation start site and a protein that differs in length by three amino acids (T = 427aa, C = 424aa; rs10735810). MATERIALS AND METHODS: We conducted genetic association analyses of this polymorphism, BMD, and fracture outcomes in a prospective cohort of 6698 white American women >or=65 years of age. Incident fractures were confirmed by physician adjudication of radiology reports. There were 2532 incident nontraumatic/nonvertebral fractures during 13.6 yr of follow-up including 509 wrist and 703 hip fractures. RESULTS: Women with the C/C genotype had somewhat lower distal radius BMD compared with those with the T/T genotype (CC=0.358 g/cm(2), CT=0.361 g/cm(2), TT=0.369 g/cm(2), p=0.003). The C/C genotype was also associated with increased risk of non-spine, low traumatic fractures (HR: 1.18; 95% CI: 1.04, 1.33) and wrist fractures (HR: 1.33; 95% CI: 1.01, 1.75) compared with the T/T genotype in age-adjusted models. Further adjustments for distal radius BMD only slightly attenuated these associations. The VDR polymorphism was not associated with hip fracture. The population attributable risk (PAR) of the C/C genotype for incident fractures was 6.1%. The PAR for established risk factors for fracture were: low femoral neck BMD (PAR=16.3%), maternal history of fracture (PAR=5.1%), low body weight (PAR=5.3%), corticosteroid use (PAR=1.3%), and smoking (PAR=1.6%). Similar PAR results were observed for wrist fractures. CONCLUSIONS: The common and potentially functional VDR translation start site polymorphism confers a modestly increased relative risk of fracture among older white women. However, the high frequency of this variant confers a population attributable risk that is similar to or greater than several established risk factors for fracture. PMID- 17280525 TI - Genetic and epigenetic mechanisms for gene expression and phenotypic variation in plant polyploids. AB - Polyploidy, or whole-genome duplication (WGD), is an important genomic feature for all eukaryotes, especially many plants and some animals. The common occurrence of polyploidy suggests an evolutionary advantage of having multiple sets of genetic material for adaptive evolution. However, increased gene and genome dosages in autopolyploids (duplications of a single genome) and allopolyploids (combinations of two or more divergent genomes) often cause genome instabilities, chromosome imbalances, regulatory incompatibilities, and reproductive failures. Therefore, new allopolyploids must establish a compatible relationship between alien cytoplasm and nuclei and between two divergent genomes, leading to rapid changes in genome structure, gene expression, and developmental traits such as fertility, inbreeding, apomixis, flowering time, and hybrid vigor. Although the underlying mechanisms for these changes are poorly understood, some themes are emerging. There is compelling evidence that changes in DNA sequence, cis- and trans-acting effects, chromatin modifications, RNA mediated pathways, and regulatory networks modulate differential expression of homoeologous genes and phenotypic variation that may facilitate adaptive evolution in polyploid plants and domestication in crops. PMID- 17280527 TI - Effect of growth hormone replacement on BMD in adult-onset growth hormone deficiency. AB - To determine if replacement of GH improves BMD in adult-onset GHD, we administered GH in physiologic amounts to men and women with GHD. GH replacement significantly increased spine BMD in the men by 3.8%. INTRODUCTION: Growth hormone (GH) deficiency (GHD) acquired in adulthood results in diminished BMD; the evidence that replacement of GH improves BMD is not conclusive. We therefore performed a randomized, placebo-controlled trial to determine whether GH replacement would increase lumbar spine BMD in a combined group of men and women with adult-onset GHD. MATERIALS AND METHODS: We randomized 67 men and women to receive GH (n=33) or placebo (n=34) for 2 yr. The GH dose was initially 2 microg/kg body weight/d, increased gradually to a maximum of 12 microg/kg/d and adjusted to maintain a normal IGF-I concentration for age and sex. BMD was assessed before treatment and at 6, 12, 18, and 24 mo of treatment. Fifty-four subjects completed the protocol. RESULTS: BMD of the lumbar spine in the entire group increased by 2.9 +/- 3.9% above baseline in the GH-treated subjects, which was significantly (p=0.037) greater than the 1.4 +/- 4.5% increase in the placebo treated subjects. In a secondary analysis, spine BMD in GH-treated men increased 3.8 +/- 4.3% above baseline, which was significantly (p=0.001) greater than that in placebo-treated men (0.4 +/- 4.7%), but the change in GH-treated women was not significantly different from that in placebo-treated women. Treatment with GH did not increase total hip BMD more than placebo treatment after 2 yr. CONCLUSIONS: We conclude that GH replacement in men who have adult-onset GHD improves their spine BMD, but we cannot draw any conclusions about the effect of GH replacement on spine BMD in women with adult-onset GHD. PMID- 17280528 TI - Seasonal change in osteoid thickness and mineralization lag time in ambulant patients. AB - Low vitamin D levels are common. Bone biopsies taken from 121 ambulant patients were therefore reviewed. Seasonal changes in mineralization correlated inversely with serum 25-hydroxyvitamin D but not the more active metabolite, 1,25 dihydroxyvitamin D. This implies that the latter is produced in bone. INTRODUCTION: It has been 30 yr since a seasonal variation in osteoid surfaces and calcification fronts was noted in bone biopsies from hip fracture patients in Leeds and attributed to vitamin D status. It was suggested at that time that mild vitamin D deficiency might cause osteoporosis from malabsorption of calcium and more severe deficiency osteomalacia, but little has been published on this subject since. MATERIALS AND METHODS: We examined bone biopsies, calcium absorption data, and serum vitamin D metabolites in 121 patients attending our osteoporosis clinics in Adelaide. Biopsies were collected from the anterior iliac crest with a Jamshidi needle after two stat oral doses of 1 g of tetracycline 10 days apart, processed into plastic without demineralization, and all parameters were measured by point counting using a Weibel II graticule. Calcium absorption was measured after an oral dose of 5 microCi of (45)Ca in 250 ml of water with 20 mg of calcium carrier. Serum 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] by radioimmunoassay after high-performance liquid chromatography (HPLC). RESULTS: 25(OH)D levels were lower from late autumn to early spring (April to September) than from late spring to early autumn (October to March) (51 +/- 23 versus 61 +/- 27 [SD] nM; p=0.040). None of the biopsies yielded a diagnosis of osteomalacia, but osteoid thickness (O.Th.) was greater in the winter than the summer months (8.5 +/- 3.6 versus 7.1 +/- 2.8 microm; p=0.015) as was mineralization lag time (MLT; 11.9 +/- 5.2 versus 9.5 +/- 3.6; p=0.005). O.Th and log MLT were both inversely related to serum 25(OH)D (p=0.014 and 0.036) but not serum 1,25(OH)(2)D. Calcium absorption was related to serum 1,25(OH)(2)D but not serum 25(OH)D. CONCLUSIONS: We conclude that circulating 25(OH)D affects the mineralization process, whereas circulating 1,25(OH)(2)D affects bone indirectly through its effect on calcium absorption. PMID- 17280530 TI - Summary of the International Society For Clinical Densitometry 2005 Position Development Conference. PMID- 17280531 TI - Designing drug-delivery systems for the nervous system using nanotechnology: opportunities and challenges. PMID- 17280532 TI - Concerns over safety of drug-eluting stents. PMID- 17280533 TI - NIH Neural Interfaces Workshop: August 21-23, 2006, Bethesda, MD, USA. PMID- 17280534 TI - SPECT/CT with a hybrid camera: a new imaging modality for the functional anatomical mapping of infections. AB - Evaluation of: Bar-Shalom R, Yefremov N, Guralnik L et al. SPECT/CT using (67)Ga and (111)In-labeled leukocyte scintigraphy for diagnosis of infection. J. Nucl. Med. 47(4), 587-594 (2006). Labeled leukocytes and (67)Ga scan have been proved to be useful to image infectious and inflammatory processes. However, it is well known that nuclear imaging lacks precise anatomical landmarks. When highly specific tracers are used, the background activity may be too low to be used as a framework for spatial orientation. To overcome these drawbacks, the hybrid devices combining positron emission tomography/single photon emission computed tomography (SPECT) and computed tomography (CT) have been introduced, thereby providing a precise anatomical-functional correlation. The paper under evaluation highlights the emerging role of hybrid SPECT/CT to image infection with labeled leukocytes and (67)Ga. The authors suggest that fusion imaging can be of paramount value to locate the site of infection and to better define the extent of disease. PMID- 17280535 TI - Onyx: a unique neuroembolic agent. AB - Rupture of a cerebral arteriovenous malformation can result in devastating hemorrhage with a possibility of serious neurological injury or death. Endovascular embolization is an important adjunct in the treatment of cerebral arteriovenous malformations, and in a small number of cases may provide definitive treatment. Currently available embolic agents have several shortcomings, including the possibility of recanalization, adhesiveness to the endovascular microcatheter and suboptimal handling at the time of surgical resection. Onyx is an ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide that was approved by the US FDA in July 2005 as an embolic agent for brain arteriovenous malformations. Although long-term follow-up is limited, this agent appears to offer several advantages over the other available embolic agents for the endovascular management of arteriovenous malformations and other vascular lesions. PMID- 17280536 TI - Sonablate-500: transrectal high-intensity focused ultrasound for the treatment of prostate cancer. AB - Prostate cancer (PCa) is the most common cancer in men and the second leading cause of death from malignancy in the UK. The number of men diagnosed with PCa is increasing, due in part to an increased willingness of men to visit their family doctors with lower urinary tract symptoms, and also a willingness of physicians to test for it. As the demographic of men diagnosed with PCa becomes younger and better informed, so the demand for a less-invasive alternative to standard therapies becomes greater. The Sonablate-500 is one of only two high-intensity focused ultrasound (HIFU) devices commercially available to treat PCa. HIFU is an attractive treatment option as it is the only form of therapy that neither involves direct instrumentation of the prostate nor ionizing radiation. This article describes the unique features of both the Sonablate-500 system hardware and software, and the outcome data from this device in the context of current standard therapies. Finally, a view into the future attempts to outline where this technology is heading and how a paradigm shift in the way that PCa is considered may make HIFU even more relevant. PMID- 17280537 TI - BioMatrix Biolimus A9-eluting coronary stent: a next-generation drug-eluting stent for coronary artery disease. AB - Drug-eluting stent technology consisting of a bare metal stent, carrier coating, bioactive drug and delivery system, offers an almost infinite range of possible device configurations. A growing understanding of the mechanisms of restenosis allows for the design of synergistic functions within these components, thus providing a basis for new and improved products. The BioMatrix stent (Biosensors Interventional Technologies Pte Ltd., Singapore) elutes the new sirolimus derivative Biolimus A9 from a biodegradable polylactic acid polymer. Biolimus A9 possesses enhanced anti-inflammatory and antiproliferative activity with an improved pharmacokinetic profile. Permanent polymer-carrier-based platforms may be associated with inflammation, late thrombosis and restenosis. The BioMatrix, with its asymmetric and abluminal coating, releases Biolimus A9 into the vessel wall while the polylactic acid polymer is resorbed by surrounding tissues. Clinical studies have demonstrated the BioMatrix to be well tolerated and effective, and it has now become the subject of an aggressive clinical program. PMID- 17280539 TI - US FDA perspective on regulatory issues affecting circulatory assist devices. AB - There has been a rapid development in mechanical circulatory support systems in the decade since the US FDA first approved a mechanical device to provide the circulatory support lacking from a failing heart. Devices are presently approved for marketing by the FDA to replace a failing ventricle, the Ventricular Assist Device or the entire heart, Total Artificial Heart. Contemporaneous with, and permitted by, improvement in technology and design, devices have evolved from units located extracorporeally to paracorporeal systems and totally implanted devices. Clinical studies have demonstrated a parallel improvement in the homeostatic adequacy of the circulatory support provided. Thus, while the circulatory support was initially tolerated for short periods to permit recovery of cardiac function, this technology eventually provided effective circulatory support for increasing periods that permitted the FDA to approve devices for bridging patients in end-stage cardiac failure awaiting transplant and eventually a device for destination therapy where patients in end-stage heart failure are not cardiac transplant candidates. The approved devices have relied on displacement pumps that mimic the pulsatility of the physiological system. Accelerated development of more compact devices that rely on alternative pump mechanisms have challenged both the FDA and device manufacturers to assure that the regulatory requirements for safety and effectiveness are met for use of mechanical circulatory support systems in expanded target populations. An FDA regulatory perspective is reviewed of what can be a potentially critical healthcare issue. PMID- 17280538 TI - A preclinical study of nonsurgical radiofrequency collagen remodeling for the treatment of stress urinary incontinence. AB - Many women with stress urinary incontinence seek a nonsurgical, well-tolerated, effective and durable treatment that is associated with a rapid recovery and improvement in quality of life. However, the nonsurgical options available, such as pelvic floor exercises or behavioral therapy, are typically not effective; thus, many women with the condition remain untreated. A new nonsurgical treatment, transurethral radiofrequency collagen remodeling, offers many patient desired treatment characteristics. This prospective, controlled animal study was performed to evaluate the safety, gross and histological impact, and physiological effect of transurethral radiofrequency collagen remodeling. The outcomes served as the basis for initial and subsequent clinical trials in women. PMID- 17280540 TI - Resurrection of hip resurfacing: what is the evidence? AB - Total hip resurfacing has long been conceptually attractive to both surgeons and patients. However, historically it has been plagued by limited durability and marked acetabular bone loss. The recent development of wear-resistant bearings, such as metal-on-metal, has led to renewed interest in hip resurfacing in the orthopedic community. Several resurfacing implants have been designed and positive results, particularly in young patients, have been reported. Although comparative studies of hip resurfacing and standard total hip replacement are still lacking, we believe that there is now evidence to demonstrate that this surgical concept deserves consideration, particularly when treating young patients with hip diseases. PMID- 17280541 TI - Computer-assisted osteodensitometry following total hip arthroplasty. AB - Several factors, including polyethylene wear debris, implant micromotion and stress shielding, can cause bone loss and fixation failure following total hip arthroplasty. Various techniques have been utilized in an effort to detect bone density loss in vivo with varying success. Quantitative computed tomography (qCT) assisted osteodensitometry has been shown to be useful in assessing the in vivo structural bone changes after total hip arthroplasty. It has high resolution, accuracy and reproducibility, making it a useful tool for research purposes. qCT osteodensitometry is able to differentiate between cortical and cancellous bone structures, and to assess the bone/implant interface. It provides valuable information about the pattern of stress shielding that occurs around the prosthesis. qCT-assisted osteodensitometry can show early bony changes, which may provide information about the quality of implant fixation and surrounding bone adaptation. In conjunction with finite-elements analysis, qCT is able to generate accurate patient-specific meshes on which to model implants and their effect on bone remodeling. This technology can be useful in order to predict bone remodeling and quality of implant fixation using prostheses with different design and/or biomaterials. In future, this tool could be used for preclinical validation of new implants before their introduction in the marketplace. PMID- 17280542 TI - Implants for total hip arthroplasty. AB - This article is a comprehensive review of the published literature on total hip replacement design. It seeks to provide a nonbiased view of the technology related to total hip implants and bearing surfaces. Implant designs and fixation methods are discussed with summaries of their respective long-term outcome studies. Fixation methods include cemented, cementless and hybrid techniques and are explained and presented with current outcome data and their respective failure modes that have promoted new technological development. The current data point toward cementless acetabular fixation as being superior to cemented fixation. As for stem fixation, there are good data to suggest that either method of fixation is acceptable in the proper setting. Also included in this article is a brief review of bearing surfaces and hip biomechanics. PMID- 17280543 TI - Laparoscopic adrenalectomy for the management of benign and malignant adrenal tumors. AB - Laparoscopic adrenalectomy has become the preferred approach for removal of the adrenal gland. Many published studies support the use of laparoscopic adrenalectomy, with comparisons to open adrenalectomy suggesting many advantages to laparoscopy, including less postoperative pain, shorter hospital stay and earlier return to work. Adrenalectomy is usually required for the removal of adrenal tumors causing excess hormone production or because a malignant adrenal tumor cannot be excluded. Current controversies include the appropriateness of laparoscopic adrenalectomy for large or malignant tumors, the role of partial adrenalectomy and the management of some conditions with uncertain natural history (such as subclinical hypercortisolism). With the increased use of sensitive cross-sectional imaging, the detection of clinically inapparent adrenal masses is likely to continue to increase. Due to the fact that malignancy cannot be excluded with certainty in some patients with cortical adenomas, it is expected that the rate of laparoscopic adrenalectomy will continue to increase. PMID- 17280544 TI - Optical diagnostic technology based on light scattering spectroscopy for early cancer detection. AB - This article reviews the application of optical diagnostic technology based on light scattering spectroscopy for minimally invasive detection of precancerous and early cancerous changes in a variety of organs. Optical spectroscopic techniques have shown promising results in the diagnosis of diseases at the cellular scale. They do not require tissue removal, can be performed in vivo and allow for real-time diagnosis. While fluorescence and Raman spectroscopy are most effective in revealing the molecular properties of tissue, the novel technique, light scattering spectroscopy, is capable of characterizing the structural properties of tissue at the cellular and subcellular scale. PMID- 17280545 TI - Orbital implants: potential new directions. AB - This article reviews orbital implants used to replace an eye after enucleation or evisceration. Advantages of implant placement are described, with discussion of implant and wrap material, and design features that affect clinical outcomes. Implants may be porous or nonporous, pegged for linkage with a cosmetic shell or unpegged, and may be wrapped with a covering material or tissue or unwrapped. Device shape, volume and material qualities affect tissue tolerance and the risk of exposure or extrusion. Limitations of currently available devices are discussed, with factors affecting surgeon and patient choice. Ideally, a device should be easy to insert, avoid the need for wrapping or adjunctive tissues, be light, biointegratable, comfortable after implantation and provide satisfactory orbital volume replacement, movement and cosmesis without requiring further surgery or pegging. This review briefly discusses developments in implant design and aspects of design that affect function, but is not a detailed clinical review; rather, it aims to stimulate thought on optimal design and discusses recent developments. Novel technology in the form of a prototype device with a soft, biointegratable anterior surface is described as an example of newer approaches. PMID- 17280546 TI - Bioprosthetic heart valve heterograft biomaterials: structure, mechanical behavior and computational simulation. AB - The present review surveys significant developments in the biomechanical characterization and computational simulation of biologically derived chemically cross-linked soft tissues, or 'heterograft' biomaterials, used in replacement bioprosthetic heart valve (BHV). A survey of mechanical characterization techniques, relevant mechanical properties and computational simulation approaches is presented for both the source tissues and cross-linked biomaterials. Since durability remains the critical problem with current bioprostheses, changes with the mechanical behavior with fatigue are also presented. Moreover, given the complex nature of the mechanical properties of heterograft biomaterials it is not surprising that most constitutive (stress strain) models, historically used to characterize their behavior, were oversimplified. Simulations of BHV function utilizing these models have inevitably been inaccurate. Thus, more recent finite element simulations utilizing nonlinear constitutive models, which achieve greater model fidelity, are reviewed. An important conclusion of this review is the need for accurate constitutive models, rigorously validated with appropriate experimental data, in order that the design benefits of computational models can be realized. Finally, for at least the coming 20 years, BHVs fabricated from heterograft biomaterials will continue to be extensively used, and will probably remain as the dominant valve design. We should thus recognize that rational, scientifically based approaches to BHV biomaterial development and design can lead to significantly improved BHV, over the coming decades, which can potentially impact millions of patients worldwide with heart valve disease. PMID- 17280547 TI - Design and preparation of polymeric scaffolds for tissue engineering. AB - Polymeric scaffolds for tissue engineering can be prepared with a multitude of different techniques. Many diverse approaches have recently been under development. The adaptation of conventional preparation methods, such as electrospinning, induced phase separation of polymer solutions or porogen leaching, which were developed originally for other research areas, are described. In addition, the utilization of novel fabrication techniques, such as rapid prototyping or solid free-form procedures, with their many different methods to generate or to embody scaffold structures or the usage of self assembly systems that mimic the properties of the extracellular matrix are also described. These methods are reviewed and evaluated with specific regard to their utility in the area of tissue engineering. PMID- 17280548 TI - Biomedical applications of polyhydroxyalkanoates: an overview of animal testing and in vivo responses. AB - Polyhydroxyalkanoates (PHAs) have been established as biodegradable polymers since the second half of the twentieth century. Altering monomer composition of PHAs allows the development of polymers with favorable mechanical properties, biocompatibility and desirable degradation rates, under specific physiological conditions. Hence, the medical applications of PHAs have been explored extensively in recent years. PHAs have been used to develop devices, including sutures, nerve repair devices, repair patches, slings, cardiovascular patches, orthopedic pins, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, bone-marrow scaffolds, tissue engineered cardiovascular devices and wound dressings. So far, various tests on animal models have shown polymers, from the PHA family, to be compatible with a range of tissues. Often, pyrogenic contaminants copurified with PHAs limit their pharmacological application rather than the monomeric composition of the PHAs and thus the purity of the PHA material is critical. This review summarizes the animal testing, tissue response, in vivo molecular stability and challenges of using PHAs for medical applications. In future, PHAs may become the materials of choice for various medical applications. PMID- 17280549 TI - Amide solvent protection analysis demonstrates that amyloid-beta(1-40) and amyloid-beta(1-42) form different fibrillar structures under identical conditions. AB - AD (Alzheimer's disease) is a neurodegenerative disorder characterized by self assembly and amyloid formation of the 39-43 residue long Abeta (amyloid-beta) peptide. The most abundant species, Abeta(1-40) and Abeta(1-42), are both present within senile plaques, but Abeta(1-42) peptides are considerably more prone to self-aggregation and are also essential for the development of AD. To understand the molecular and pathological mechanisms behind AD, a detailed knowledge of the amyloid structures of Abeta-peptides is vital. In the present study we have used quenched hydrogen/deuterium-exchange NMR experiments to probe the structure of Abeta(1-40) fibrils. The fibrils were prepared and analysed identically as in our previous study on Abeta(1-42) fibrils, allowing a direct comparison of the two fibrillar structures. The solvent protection pattern of Abeta(1-40) fibrils revealed two well-protected regions, consistent with a structural arrangement of two beta-strands connected with a bend. This protection pattern partly resembles the pattern found in Abeta(1-42) fibrils, but the Abeta(1-40) fibrils display a significantly increased protection for the N-terminal residues Phe4-His14, suggesting that additional secondary structure is formed in this region. In contrast, the C-terminal residues Gly37-Val40 show a reduced protection that suggests a loss of secondary structure in this region and an altered filament assembly. The differences between the present study and other similar investigations suggest that subtle variations in fibril-preparation conditions may significantly affect the fibrillar architecture. PMID- 17280552 TI - Mediators of tubuloglomerular feedback regulation of glomerular filtration: ATP and adenosine. AB - In the juxtaglomerular apparatus of the kidney the loop of Henle gets into close contact to its parent glomerulus. This anatomical link between the tubular system and the vasculature of the afferent and efferent arteriole enables specialized tubular cells, the macula densa (MD) cells, to establish an intra-nephron feedback loop designed to control preglomerular resistance and thereby single nephron glomerular filtration rate. This review focuses on the signalling mechanisms which link salt-sensing MD cells and the regulation of preglomerular resistance, a feedback loop known as tubuloglomerular feedback (TGF). Two purinergic molecules, ATP and adenosine, have emerged over the years as most likely candidates to serve as mediators of TGF. Data will be reviewed supporting a role of either ATP or adenosine as mediators of TGF. In addition, a concept will be discussed that integrates both ATP and adenosine into one signalling cascade that includes (i) release of ATP from MD cells upon increases in tubular salt concentration, (ii) extracellular degradation of ATP to form adenosine, and (iii) adenosine-mediated vasoconstriction of the afferent arteriole. PMID- 17280553 TI - Hepatic pre-sinusoidal vessels contract in anaphylactic hypotension in rabbits. AB - AIM: The purpose of this study was to determine whether anaphylactic hypotension in rabbits is accompanied by hepatic venoconstriction, and the effects of anaphylaxis on hepatic segmental vascular resistances and liver weight in isolated perfused rabbit livers. METHODS: The rabbits were sensitized by subcutaneous injection of antigen of 2.5 mg ovalbumin with complete Freund's adjuvant three times at 1 week interval. One week after sensitization, anaphylaxis was induced by an injection of 2.5 mg ovalbumin into the jugular vein of pentobarbital anaesthetized rabbits or the perfusate of rabbit livers perfused via the portal vein at a constant flow. Using the double occlusion technique to estimate the hepatic sinusoidal pressure, pre- (R(pre)) and post-sinusoidal (R(post)) resistances were calculated for the isolated perfused livers. RESULTS: An antigen injection into the sensitized rabbits caused not only a decrease in systemic arterial pressure from 79 +/- 2 to 40 +/- 4 mmHg, but also an increase in portal venous pressure (P(pv)) from 9.5 +/- 2.2 to 24.1 +/- 3.9 cmH(2)O. Portal hypertension persisted for 8 min after the antigen injection. An injection of antigen into the perfusate caused a marked increase in P(pv) from 5.4 +/- 0.1 to 28.6 +/- 2.4 cmH(2)O at 6 min, but only a slight increase in double occlusion pressure from 2.2 +/- 0.2 to 3.8 +/- 0.2 cmH(2)O, resulting in a selective increase in R(pret) rather than R(post). Concomitant with the hepatic pre sinusoidal constriction, liver weight loss occurred. CONCLUSION: Anaphylactic hypotension in rabbits is accompanied by hepatic venoconstriction which is characterized by pre-sinusoidal contraction. PMID- 17280554 TI - Oestrogen modulates cardiac ischaemic remodelling through oestrogen receptor specific mechanisms. AB - AIM: Observational and clinical studies suggest different responses upon sex hormone replacement therapy in ischaemic heart disease. Few studies, however, have examined the impact of oestrogen receptor-dependent mechanisms on the extent of injury after myocardial infarction (MI). Therefore, we set out to evaluate the effect of oestrogen (E2) replacement on infarct size and remodelling, and the respective role of the oestrogen receptors (ER)alpha and -beta in this process, using ERalpha- and ERbeta-deficient mice. METHODS: Wild type (WT) (ERalpha(+/+) and ERbeta(+/+)), ERalpha-deficient (ERalpha(-/-)) and ERbeta-deficient (ERbeta( /-)) mice were ovariectomized and subsequently supplemented with E2 or placebo using subcutaneous 60-day release pellets. MI was induced by left coronary artery ligation. Two weeks following MI, haemodynamic function was assessed and infarct size was determined. RESULTS: There was no significant difference in infarct size between E2- or placebo-treated WT (ERalpha(+/+) and ERbeta(+/+)) mice. Surprisingly, E2 treatment did result in smaller infarct sizes in ERalpha(-/-) mice, but increased the infarct size in ERbeta(-/-) mice. Increase of the left ventricular mass post-MI was significantly larger in the E2-treated ERalpha(-/-) animals compared with placebo-treated animals. E2 treatment also significantly increased post-MI mortality in ERalpha(+/+), ERbeta(+/+) and ERalpha(-/-) animals, but not in ERbeta(-/-) mice. CONCLUSIONS: Although E2 modulates the infarct size in ERalpha(-/-), it also appears to be responsible for the higher mortality following MI. ERbeta appears to be the receptor involved in the modulating effects of E2 in the infarcted heart. PMID- 17280556 TI - Expression of oestrogen receptors alpha and beta during the period of uterine receptivity in rat: effect of ormeloxifene, a selective oestrogen receptor modulator. AB - AIMS: In the present study, we investigated expression, distribution and regulation of oestrogen receptors (ERs) alpha and beta and their modulation by ormeloxifene (Orm) during the period of uterine receptivity in rat uterus in order to determine their role in endometrial sensitization. METHODS: Uterine tissues of control and Orm-treated (1.25 mg kg(-1), orally) rats were collected on days 3, 4, 5 morning and day 5 evening post-coitum referring to non-receptive, pre-receptive and receptive phases respectively. mRNA and protein expression levels were determined by RT-PCR and Western blot respectively. Immunohistochemical technique was used to localize the receptors. RESULTS: RT-PCR analysis revealed that ERalpha mRNA reached a peak level on day 5 morning whereas ERbeta mRNA expression was found to be very low. In Orm-treated rats, the ERalpha mRNA was suppressed at day 5. The protein expression of ERalpha increased after day 3 and that of ERbeta remained very low throughout the pre-implantation period; Orm caused a decrease in ERalpha on day 5 morning. In endometrium, ERalpha expression was regulated differentially in luminal epithelium, glandular epithelium and stroma. Orm caused a decrease in the percentage of ERalpha positive nuclei in all the three endometrial compartments on days 4 and 5, and the magnitude of reduction varied spatio-temporally. In case of ERbeta, immunostaining was not detectable in Orm-treated and control groups. CONCLUSION: It appears that the complex uterine response to implantation is governed by differential cell-specific ERalpha expression. The study suggested the inhibitory activity of Orm on ERalpha during the period of uterine receptivity. PMID- 17280555 TI - Arrhythmogenic mechanisms in the isolated perfused hypokalaemic murine heart. AB - AIM: Hypokalaemia is associated with a lethal form of ventricular tachycardia (VT), torsade de pointes, through pathophysiological mechanisms requiring clarification. METHODS: Left ventricular endocardial and epicardial monophasic action potentials were compared in isolated mouse hearts paced from the right ventricular epicardium perfused with hypokalaemic (3 and 4 mm [K(+)](o)) solutions. Corresponding K(+) currents were compared in whole-cell patch-clamped epicardial and endocardial myocytes. RESULTS: Hypokalaemia prolonged epicardial action potential durations (APD) from mean APD(90)s of 37.2 +/- 1.7 ms (n = 7) to 58.4 +/- 4.1 ms (n =7) and 66.7 +/- 2.1 ms (n = 11) at 5.2, 4 and 3 mm [K(+)](o) respectively. Endocardial APD(90)s correspondingly increased from 51.6 +/- 1.9 ms (n = 7) to 62.8 +/- 2.8 ms (n = 7) and 62.9 +/- 5.9 ms (n = 11) giving reductions in endocardial-epicardial differences, DeltaAPD(90), from 14.4 +/- 2.6 to 4.4 +/- 5.0 and -3.4 +/- 6.0 ms respectively. Early afterdepolarizations (EADs) occurred in epicardia in three of seven spontaneously beating hearts at 4 mm [K(+)](o) with triggered beats followed by episodes of non-sustained VT in nine of 11 preparations at 3 mm. Programmed electrical stimulation never induced arrhythmic events in preparations perfused with normokalemic solutions yet induced VT in two of seven and nine of 11 preparations at 4 and 3 mm [K(+)](o) respectively. Early outward K(+) current correspondingly fell from 73.46 +/- 8.45 to 61.16+/-6.14 pA/pF in isolated epicardial but not endocardial myocytes (n = 9) (3 mm [K(+)](o)). CONCLUSIONS: Hypokalaemic mouse hearts recapitulate the clinical arrhythmogenic phenotype, demonstrating EADs and triggered beats that might initiate VT on the one hand and reduced transmural dispersion of repolarization reflected in DeltaAPD(90) suggesting arrhythmogenic substrate on the other. PMID- 17280557 TI - Gastrocnemius muscle-tendon behaviour during walking in young and older adults. AB - AIM: Age-related differences in muscle architectural and tendon mechanical properties have been observed in vivo under static conditions and during single joint contractions. The aim of this study was to determine if there are age related differences in gastrocnemius fascicle-tendon interactions during a fundamental locomotor task - walking. METHODS: Eight young adults (YA; 27 +/- 4 years) and eight older adults (OA; 77 +/- 4 years) walked on a treadmill at 1.11 m s(-1) whilst length changes in the gastrocnemius lateralis muscle tendon complex (MTC), fascicles and tendinous tissue (TT) were determined from joint angles, ultrasonography and a geometric MTC model (combining MTC and fascicle measurements) respectively. RESULTS: There was no age-related difference in lengthening of the MTC during stance. However, the fascicle and TT contribution to MTC lengthening was altered; TT lengthening was larger in OA than in YA (P = 0.05) and fascicle lengthening was less in OA than YA (P < 0.05). There were no differences between groups in MTC, fascicle or TT shortening amplitude during push-off. CONCLUSION: The observations are consistent with previous reports of increased compliance of TT in older adults. PMID- 17280558 TI - Relief of chronic partial ureteral obstruction attenuates salt-sensitive hypertension in rats. AB - AIM: The incidence of hydronephrosis due to ureteropelvic junction obstruction is approx. 0.5%. During the last decade, the management of non-symptomatic hydronephrosis has become much more conservative, but the long-term physiological consequences of this policy are not clear. Previously, we have shown that animals with chronic partial unilateral ureteral obstruction develop salt-sensitive hypertension. In this study, the effects of ipsilateral and contralateral nephrectomy and ureterovesicostomy on blood pressure were studied in hydronephrotic animals. METHODS: Partial unilateral ureteral obstruction was created in 3-week-old male Sprague-Dawley rats and blood pressure was measured telemetrically 4-6 weeks later during a normal and high salt diet before and after uninephrectomy or ureterovesicostomy. Plasma samples for renin assay were collected during both diets before and after ipsilateral nephrectomy. RESULTS: All hydronephrotic animals developed salt-sensitive hypertension, of different degrees. Before nephrectomy the plasma renin concentration was significantly higher in the hydronephrotic animals than in controls (160 +/- 15 microGU mL(-1) vs. 96 +/- 12 microGU mL(-1), respectively), but after the ipsilateral nephrectomy no differences were found between the groups. In the hydronephrotic animals both ipsilateral nephrectomy and ureterovesicostomy reduced the blood pressure and salt-sensitivity but the former still differed significantly from the controls. In contralaterally, nephrectomized hydronephrotic animals the salt sensitive hypertension became more pronounced. CONCLUSION: Hydronephrosis in rats causes salt-sensitive hypertension that can be markedly reduced by removing the hydronephrotic kidney or relieving the obstruction by ureterovesicostomy. The mechanisms appear to be intrarenal and primarily located in the diseased kidney, but a secondary mechanism is also present. PMID- 17280559 TI - Effects of ATP on rat renal haemodynamics and excretion: role of sodium intake, nitric oxide and cytochrome P450. AB - AIM: Adenosine-5'-triphosphate (ATP) affects intrarenal vascular tone and tubular transport via P2 receptors; however, the actual role of the system in regulation of renal perfusion and excretion remains unclear and is the subject of this whole kidney study. METHODS: Effects of suprarenal aortic ATP infusion, 0.6-1.2 mg kg( 1) h(-1), were examined in anaesthetised rats maintained on low- (LS) or high sodium (HS) diet. Renal artery blood flow (RBF, transonic flow probe) and the perfusion (laser-Doppler flux) of the superficial cortex (CBF) and outer and inner medulla (OM-BF, IM-BF) were measured, together with sodium and water excretion and urine osmolality. RESULTS: Adenosine-5'-triphosphate did not change arterial pressure, RBF or CBF while the effects on medullary perfusion depended on sodium intake. In LS rats ATP increased IM-BF 19 +/- 6%, the effect was prevented by inhibition of nitric oxide (NO) with N-nitro-l-arginine methyl ester. In HS rats ATP decreased OM-BF 16 +/- 3% and IM-BF (7 +/- 4%, not significant); previous inhibition of cytochrome P450 with 1-aminobenzotriazol blunted the OM-BF decrease and reversed the previous decrease of IM-BF to a 13 +/ 8% increase. Inhibition of P2 receptors with pyridoxal derivative (PPADS) abolished medullary vascular responses to ATP. In HS rats pre-treated with PPADS, ATP increased tubular reabsorption, probably via adenosine formation and stimulation of P1 receptors. CONCLUSION: The data indicate a potential role of ATP in the selective control of renal medullary perfusion, different in sodium depleted and sodium replete rats. The action of ATP appears to be mediated by the NO system and the cytochrome P450 dependent vasoactive metabolites. PMID- 17280560 TI - Determination of ethane, pentane and isoprene in exhaled air--effects of breath holding, flow rate and purified air. AB - AIM: Exhaled ethane, pentane and isoprene have been proposed as biomarkers of oxidative stress. The objectives were to explore whether ethane, pentane and isoprene are produced within the airways and to explore the effect of different sampling parameters on analyte concentrations. METHODS: The flow dependency of the analyte concentrations, the concentrations in dead-space and alveolar air after breath-holding and the influence of inhaling purified air on analyte concentrations were investigated. The analytical method involved thermal desorption from sorbent tubes and gas chromatography. The studied group comprised 13 subjects with clinically stable asthma and 14 healthy controls. RESULTS: Ethane concentrations decreased slightly, but significantly, at higher flow rates in subjects with asthma (P = 0.0063) but not in healthy controls. Pentane levels were increased at higher flow rates both in healthy and asthmatic subjects (P = 0.022 and 0.0063 respectively). Isoprene levels were increased at higher flow rates, but only significantly in healthy subjects (P = 0.0034). After breath holding, no significant changes in ethane levels were observed. Pentane and isoprene levels increased significantly after 20 s of breath-holding. Inhalation of purified air before exhalation resulted in a substantial decrease in ethane levels, a moderate decrease in pentane levels and an increase in isoprene levels. CONCLUSION: The major fractions of exhaled ethane, pentane and isoprene seem to be of systemic origin. There was, however, a tendency for ethane to be flow rate dependent in asthmatic subjects, although to a very limited extent, suggesting that small amounts of ethane may be formed in the airways. PMID- 17280561 TI - New method for evaluation of lung lymph flow rate with intact lymphatics in anaesthetized sheep. PMID- 17280564 TI - Melancholia: Beyond DSM, Beyond Neurotransmitters. Proceedings of a conference, May 2006, Copenhagen, Denmark. PMID- 17280565 TI - The doctrine of the two depressions in historical perspective. AB - OBJECTIVE: To determine if the concept of two separate depressions - melancholia and non-melancholia - has existed in writings of the main previous thinkers about mood disorders. METHOD: Representative contributions to writing on mood disorders over the past hundred years have been systematically evaluated. RESULTS: The concept of two separate depressions does indeed emerge in the psychiatric literature from the very beginning of modern writing about the concept of 'melancholia'. For the principal nosologists of psychiatry, melancholic depression has always meant something quite different from non-melancholic depression. Exceptions to this include Aubrey Lewis and Karl Leonhard. Yet the balance of opinion among the chief theorists overwhelmingly favors the existence of two quite different illnesses. CONCLUSION: The concept of 'major depression' popularized in DSM-III in 1980 is a historical anomaly. It mixes together psychopathologic entities that previous generations of experienced clinicians and thoughtful nosologists had been at pains to keep separate. Recently, there has been a tendency to return to the concept of two depressions: melancholic and non melancholic illness. 'Major depression' is coming into increasing disfavor. In the next edition of DSM (DSM-V), major depression should be abolished; melancholic mood disorder (MMD) and non-melancholic mood disorder (NMMD) should become two of the principle entities in the mood disorder section. PMID- 17280566 TI - Resurrecting melancholia. AB - OBJECTIVE: To define melancholia as a distinct mood disorder, identified by unremitting depressed mood, vegetative dysfunction, and psychomotor disturbances, verifiable by neuroendocrine tests, and treatable by electroconvulsive therapy and tricyclic antidepressants. METHOD: A review of the literature of two centuries finds descriptions of severe mood disorders, either depression or mania or circular, defined as 'melancholia.' In the 1980 diagnostic revision (DSM-III), melancholia was relegated to a features specifier only. RESULTS: DSM classification criteria develop heterogeneous patient samples that are neither guides to prognosis nor to treatment response, and confound studies of pathophysiology. Within the large population of mood disorders, a syndrome of melancholia is identifiable by specific behaviors, vegetative signs, and validated by neuroendocrine abnormalities (cortisolemia). Populations so identified are clinically homogeneous and have improved treatment responses. Patients meeting criteria for melancholia are now identified as psychotic depressed, geriatric depressed, postpartum psychosis, and pharmacotherapy resistant. CONCLUSION: The review supports the establishment of melancholia by empirically derived criteria rather than by a checklist is an alternative to the major depression choice and offers an improved model for psychiatric classification. PMID- 17280567 TI - Defining melancholia: the primacy of psychomotor disturbance. AB - OBJECTIVE: To argue that melancholia is a categorically distinct depressive condition, able to be differentiated from other depressive conditions by a neuropathological marker [observable psychomotor disturbance (PMD)] and having a differential response to various antidepressant treatments. METHOD: The above statements are addressed by review of a wide body of research, which identified observable PMD as the cardinal marker of melancholia and developed the CORE measure as a strategy for assessing PMD and its severity. Properties of the CORE measure, including reliability, validity and treatment prediction, are overviewed. RESULTS: A case is made for defining melancholia and a strategy for establishing its probability. CONCLUSION: Melancholia is positioned as a categorical entity capable of being circumscribed by its cardinal feature of PMD. PMID- 17280568 TI - The facets of melancholia. AB - OBJECTIVE: To clarify the role of 'melancholia' in psychiatric nomenclature. Most clinicians and researchers are convinced that the syndrome currently termed major depressive disorder encompasses multiple subgroups that differ meaningfully in phenomenology, natural history, treatment response, and pathophysiology. Delusional depression and melancholia have attracted the most empirical work, but efforts to define the latter condition have declined in recent years following a number of failures to show the validity of the melancholic/nonmelancholic distinction. METHOD: Review of experience. RESULTS: Beyond the DSM-IV symptom profile, melancholia has been associated with greater overall severity, a low likelihood of placebo response, an episodic course, a family history of depression without alcoholism, a relatively healthy personality, and hypothalamic pituitary-adrenal axis hyperactivity. Evidence for the validity of the melancholia concept lies in the fact that the presence of each of these characteristics has been shown to increase the likelihood of one or more of the others. CONCLUSION: A diagnosis of melancholia may eventually prove valuable in treatment selection, but the necessary evidence will not be forthcoming until a widely accepted definition exists that is both inherently valid and that can be applied consistently across research sites. PMID- 17280569 TI - The incidence and prevalence of manic-melancholic syndromes in North West Wales: 1875-2005. AB - OBJECTIVE: Against a background of recent interest in the concept of melancholia, we report data on the incidence and prevalence of manic, melancholic and postpartum syndromes from North West Wales. METHOD: We have utilized a database of the complete records of all admission to the North Wales Asylum from 1875 to 1924, and compared the findings for mania, melancholia, and postpartum psychoses from this sample, with admissions for these disorders to the North West Wales mental health services between 1995 and 2005. RESULTS: The incidence of bipolar disorder, as well as melancholia with and without psychotic features appears stable from 1875 to 2005 but there has been a dramatic decline in the incidence of de novo onset psychoses in the postpartum period. The prevalence of admissions for bipolar disorder, and for severe depressive disorders has increased dramatically during this period. CONCLUSION: There are some grounds for revisiting the concept of manic-melancholic disorder put forward by Rafaelsen. The changes in the incidence of postpartum psychoses may have a wider significance for the affective disorders in general. PMID- 17280570 TI - A mixed state core for melancholia: an exploration in history, art and clinical science. AB - OBJECTIVE: We argue for a mixed state core for melancholia comparing concepts of melancholia across centuries using examples from art, history and scientific literature. METHOD: Literature reviews focusing on studies from Kraepelin onward, DSM-IV classification and view-points from clinical experience highlighting phenomenologic and biologic features as predictors of bipolar outcome in prospective studies of depression. RESULTS: Despite the implied chemical pathology in the term endogenous/melancholic depression, frequently reported glucocortical and sleep neurophysiologic abnormalities, there is little evidence that melancholia is inherited independently from more broadly defined depressions. Prospective follow-up of 'neurotic' depressions have shown melancholic outcomes in as many as a third; hypomania has also been observed in such follow-up. CONCLUSION: These findings and considerations overall do suggest that melancholia as defined today is more closely aligned with the depressive and/or mixed phase of bipolar disorder. Given the high suicidality from many of these patients the practice of treating them with antidepressant monotherapy needs re-evaluation. PMID- 17280571 TI - Melancholia agitata and mixed depression. AB - OBJECTIVE: The diagnostic entity of major depressive episode includes both simple and agitated or mixed depression. Mixed depression is characterized by a full depressive episode with several symptoms of excitatory nature. Mixed depressions worsen if treated with antidepressants. METHOD: We have reviewed the clinical charts of the 2141 patients treated at the Centro Lucio Bini of Rome from January 1999 to June 2006. These patients were diagnosed according to DSM-IV criteria. Research diagnostic criteria were applied for agitated depression with motor agitation and Author's diagnostic criteria for agitated depression without motor agitation. RESULTS: One thousand and twenty-six patients had a depressive episode as index episode. Three hundred and forty six (33%) were mixed depressive states. One hundred and thirty eight (44%) of them were spontaneous; in 173 cases, the onset of the mixed depression was associated with antidepressants. CONCLUSION: Psychic and motor agitation are considered equally important for the definition of agitated depression. Treating agitated depression with antidepressants worsens the clinical picture. The use of Electroconvulsive Therapy (ECT), neuroleptics and anticonvulsants are recommended. The term Melancholia Agitata is proposed for agitated (mixed) depression. PMID- 17280572 TI - Atypical depression: current status and relevance to melancholia. AB - OBJECTIVE: The Diagnostic and Statistical Manual, Fourth Edition (DSM-IV, 1994) included atypical features as an illness specifier for major depression and dysthymia. We asked whether subsequent literature supported its validity and addressed the relationship between depression with atypical features and melancholia. METHOD: Literature review focusing on studies addressing the validity of atypical depression, supplemented by the authors' previously unpublished data. RESULTS: Most studies support the discriminant validity of depression with atypical features relative to melancholia and depression having neither melancholic nor atypical features. However, studies addressing illness course suggest that criteria for depression with atypical features define a heterogeneous patient population. CONCLUSION: DSM-IV criteria for depression with atypical features define a valid, but heterogeneous disorder. Criteria including age of onset and chronicity may define a more homogeneous group that is distinct from both melancholia and other depressed patients. PMID- 17280573 TI - Melancholia and atypical depression in the Zurich study: epidemiology, clinical characteristics, course, comorbidity and personality. AB - OBJECTIVE: A comparison of psychiatric, psychological and somatic characteristics in specified subgroups of major depressive episodes (MDE). METHOD: In a stratified community sample of young adults investigated prospectively from age 20/21 to 40/41, we defined four MDE subgroups: i) DSM-IV melancholia or atypical depression (the 'combined group'), ii) pure melancholia, iii) pure atypical depression, and iv) unspecified MDE. RESULTS: The cumulative incidence rates of the four groups were 4.1%, 7.1%, 3.5% and 8.2% respectively. Women were over represented in the combined and atypically depressed group. In 56 of 117 (47.9%) cases, melancholia was longitudinally associated with atypical MDE (n = 84) (OR = 11.9). CONCLUSION: Melancholic MDE was more severe than atypical MDE although the two groups shared many characteristics. The longitudinal overlap of melancholia with atypical depression in almost half of all cases calls for comparative analyses of combined, pure and unspecified MDE. PMID- 17280574 TI - Epidemiology of subtypes of depression. AB - OBJECTIVE: There is a general clinical impression that depression differs qualitatively from non-depressive conditions, and that it can be identified as a categorical entity. In contrast, epidemiological studies support the view that depression is dynamic in nature and develops on a continuous scale. The present article reviews selected epidemiological studies of depressive subtypes. METHOD: A selective review. RESULTS: Prior studies have found no clear differences in clinical presentation or long-term outcome between patients with melancholic and with neurotic/reactive depression. In addition, recent studies suggest that there is no clear demarcation between mild, moderate, and severe depression, pointing toward a continuity rather than categories of illness. For the individual patient, depressive symptoms seem to change over time, fulfilling criteria for major depression, minor depression, dysthymia, and subsyndromal states; the association between stressful life events and depression appears to diminish with the number of depressive episodes. Finally, recent genetic findings are congruent with a model indicating that the majority of depressions develop in the interplay between genes and stressful experiences, whereas 'reactive' depressions and 'endogenous' depressions apparently exist at a lower prevalence. CONCLUSION: Further longitudinal, analytical, and genetic epidemiologic studies are needed to reveal which conditions are mild and transient, and which may be precursors of more severe and substantial illness such as melancholia. PMID- 17280576 TI - Sleep and circadian rhythms in mood disorders. AB - OBJECTIVE: Self-reported sleep disturbances are present in over 80% of patients with depression. However, sleep electroencephalography (EEG) findings, based on overnight polysomnography have not always differentiated depressed patients from healthy individuals. METHOD: The present paper will review the findings on sleep EEG studies in depression highlighting how recent technological and methodological advances have impacted on study outcomes. RESULTS: The majority of studies, including our own work, do indicate that sleep homeostasis and sleep EEG rhythms are abnormal in depression, but the sleep disturbances were strongly moderated by gender and age. Melancholic features of depression correlated significantly with low slow-wave activity in depressed men, but not in depressed women. Women with depression showed low temporal coherence of sleep EEG rhythms but the presence or absence of melancholic features did not influence correlations. CONCLUSION: Diagnostic classification schemas and clinical features of depression may influence sleep EEG findings, but gender may be a more important consideration. PMID- 17280575 TI - Pathophysiology of hypercortisolism in depression. AB - OBJECTIVE: The mechanisms mediating hypercortisolemia in depression remain controversial. Adopting the biomarker strategy, we studied adrenocorticotropin (ACTH) and cortisol dynamics in hypercortisolemic and non-hypercortisolemic depressed in-patients, and in normal volunteers. METHOD: Deconvolution analysis of 24-h pulsatile secretion, approximate entropy (ApEn) estimation of secretory regularity, cross-ApEn quantitation of forward and reverse ACTH-cortisol synchrony, and cosine regression of 24-h rhythmicity. RESULTS: Hypercortisolemia was strongly associated with melancholic and psychotic depressive subtypes. Hypercortisolemic patients had elevated ACTH and cortisol secretion, mediated chiefly by increased burst masses. Basal ACTH secretion was increased, ACTH half life was reduced, and mean 24-h ACTH concentration was normal. Cortisol secretion was increased in a highly irregular pattern (high ApEn), with high ACTH --> cortisol cross-ApEn (impaired feedforward coupling). Cortisol-mediated feedback on the secretory pattern of ACTH was normal. Hypercortisolemic depressed patients had normal programming of the central hypothalamo-pituitary-adrenal (HPA) axis pulse generator: ACTH pulse frequency, cortisol pulse frequency, circadian acrophases, and ApEn of ACTH secretion were normal. Responsiveness of the adrenal cortex to endogenous ACTH was normal. Non-hypercortisolemic patients resembled hypercortisolemic patients on ACTH regulatory parameters but had low total cortisol secretion. CONCLUSION: Increased ACTH secretion occurs in depressed in patients regardless of cortisolemic status, confirming central HPA axis overdrive in severe depression. Depressive hypercortisolemia results from an additional change in the adrenal cortex that causes ACTH-independent, disorderly basal cortisol release, a sign of physiological stress in melancholic/psychotic depression. PMID- 17280577 TI - Does dopamine dysfunction drive depression? AB - OBJECTIVE: To examine the evidence that dopamine (DA) dysfunction contributes to melancholic depression. METHOD: Database (EMBASE, PsychLit and MEDLINE) searches using relevant key words were conducted and citations were scrutinized. RESULTS: In this paper, we assume that the definition of melancholia is contingent upon the presence of psychomotor disturbance (PMD). In melancholic depression PMD comprises both a cognitive and motor component and DA is found to be important in both. DA neurotransmission modulates cognition in particular in attention, adaptation and motivational processes and has a pivotal role in motor function. CONCLUSION: DA is a credible aetiological candidate for the PMD in melancholic depression. However, melancholia needs first to be characterized both clinically and in terms of its pathophysiology. In this regard, illnesses such as bipolar depression and Parkinson's disease warrant consideration as they provide suitable models of both the cognitive and motor aspects of PMD, and hold the necessary markers to better define melancholia. PMID- 17280578 TI - Treatment response in melancholia. AB - OBJECTIVE: Ascertain the response to specific depression treatments in melancholic and non-melancholic depressed patients. METHOD: Literature review focusing on studies addressing symptoms, diagnostic profiles, severity and other predictors of outcome with antidepressant medication, electroconvulsive therapy (ECT), psychotherapy and placebo. RESULTS: Patients with melancholia do not consistently differ from those with non-melancholic depression in their response to antidepressants and ECT, but patients with melancholia show a significantly lower rate of placebo response. Depressed patients classified as severely ill many of whom are melancholic-likewise do not differ from the less severely ill in response to antidepressants but do have a consistently lower placebo response rate. The little available data from psychotherapy studies also consistently show that melancholic and severely depressed patients are less likely than the more mildly depressed to improve with various types of psychotherapy. Depressed patients with increased pituitary-adrenocortical activity-most of whom are melancholic-show a similar pattern of treatment response: they do well with ECT and antidepressants and poorly with placebo and psychotherapies. CONCLUSION: The research data, in the aggregate, suggest that the presence of melancholia predicts a poor response to psychotherapy and placebo and a relatively good response to antidepressants and ECT. PMID- 17280579 TI - Electroconvulsive therapy in melancholia: the role of hippocampal neurogenesis. AB - OBJECTIVE: To elucidate the relationship between the effects of electroconvulsive therapy (ECT) on hippocampal anatomy and function in the therapy of melancholic depression and preclinical observations of increased neurogenesis in the hippocampus of experimental animals receiving electroconvulsive seizures (ECS). We emphasize the role of hypercortisolaemia in melancholic depression and in experimental hippocampal neurogenesis. METHOD: Our statements are based on a variety of studies pointing to i) ECT being superior to all other treatment modalities in the therapy of melancholia, ii) melancholia being associated with hypercortisolaemia and iii) evidence of hippocampal neurogenesis being relevant for understanding both melancholia and ECT. RESULTS: The increased neurogenesis found in animal studies shows stronger effect of seizures than of antidepressant drugs. The onset of effect is not only faster but is also sustained. Newborn cells are found to be functional. Suppression of neurogenesis by chronic treatment with corticosterone is associated with depression-like biology and behaviour making comparison with human depression and its response to ECT relevant. CONCLUSION: We hypothesize that the superior antimelancholic effect of induced seizures may be understood in the light of the powerful control of neural plasticity exerted by the regulation of the hypothalamic-pituitary-adrenal axis and, perhaps, other regulatory factors. PMID- 17280582 TI - Sensory transmission in the gastrointestinal tract. AB - The gastrointestinal (GI) tract must balance ostensibly opposite functions. On the one hand, it must undertake the process of digestion and absorption of nutrients. At the same time, the GI tract must protect itself from potential harmful antigenic and pathogenic material. Central to these processes is the ability to 'sense' the mechanical and chemical environment in the gut wall and lumen in order to orchestrate the appropriate response that facilitates nutrient assimilation or the rapid expulsion through diarrhoea and/or vomiting. In this respect, the GI tract is richly endowed with sensory elements that monitor the gut environment. Enteric neurones provide one source of such sensory innervation and are responsible for the ability of the decentralized gut to perform complex reflex functions. Extrinsic afferents not only contribute to this reflex control, but also contribute to homeostatic mechanisms and can give rise to sensations, under certain circumstances. The enteric and extrinsic sensory mechanisms share a number of common features but also some remarkably different properties. The purpose of this review is to summarize current views on sensory processing within both the enteric and extrinsic innervation and to specifically address the pharmacology of nociceptive extrinsic sensory pathways. PMID- 17280583 TI - In vivo and transgenic animal models used to study visceral hypersensitivity. AB - Measurement of visceral sensitivity in animals is mainly based on 'pseudoaffective' responses, which are brain stem reflexes. For example, in female, but not male rats, acute partial restraint stress induces hypersensitivity to colorectal distension. Mucosal mast cell density increases in rats after nematode infection or maternal deprivation, and both also induce colon hypersensitivity. Significantly, the proximity between nerves and mast cells has been found to be increased in adult rats submitted to maternal deprivation. Protease activation of the proteinase-activated receptor-2 also increases visceral nociception in rats, suggesting that an increase in paracellular permeability may be the primum movens in several animal models of visceral hypersensitivity. Accumulating evidence suggests that sensitization of visceral afferents is not restricted to the presumed nociceptor population, suggesting that most of the mechanosensitive afferent population can contribute to visceral discomfort and pain. Other inflammation-produced changes (e.g. subunit composition of purine-gated P2X channels) in visceral sensory neurones may also contribute to visceral hypersensitivity. This article discusses use of in vivo strategies (and transgenic mouse models) to reveal putative roles in mechanosensitivity and sensitization for molecules not previously considered to have mechanosensory functions. PMID- 17280584 TI - Peripheral and central mechanisms of visceral sensitization in man. AB - Visceral hypersensitivity (perception of gastrointestinal sensory events at a lower-than-normal threshold) is considered to be an important pathophysiological mechanism in the development of functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome, non-cardiac chest pain and functional dyspepsia. These disorders are associated with significant health care and socioeconomic costs due to factors such as repeated visits to consultants, hospitalizations and work absenteeism. Despite the presence of extensive evidence linking visceral hypersensitivity and FGIDs, the mechanism(s) underlying visceral hypersensitivity has not been fully elucidated. Suggested hypotheses include sensitization of afferent neurones, both at the level of the enteric and the (afferent) autonomic nervous system (peripheral sensitization), sensitization of spinal cord dorsal horn neurones (central sensitization) and psychosocial factors/psychiatric comorbidity influencing the processing of afferent signals at the level of the brain. Importantly, these hypotheses may be complementary rather than mutually exclusive. However, the degree to which each of these mechanisms contributes to the overall perception of visceral pain, and therefore the generation of symptoms, still remains unclear. This article discusses the mechanisms that may underlie visceral hypersensitivity, with reference to FGIDs. Understanding these mechanisms is essential in order to improve the diagnosis and treatment of patients with these disorders. PMID- 17280585 TI - Contribution of sensitivity, volume and tone to visceral perception in the upper gastrointestinal tract in man: emphasis on testing. AB - Upper gastrointestinal (GI) symptoms occur frequently in the general population, making them among the most common indications responsible for patients consulting the healthcare system. Consequently, understanding and characterization of the upper GI symptoms is important for the diagnosis and assessment of organ dysfunction. In practice, assessment of clinical symptoms is difficult and it is still to a large extent unclear how sensitivity, volume and tone contribute to visceral perception in the upper GI tract. The goal of advanced research in upper GI symptoms is to obtain a better understanding of the mechanisms involved in transduction, transmission, and perception under normal and pathophysiological conditions. An important step towards this goal is understanding the information provided by and the inherent limitations of the currently available measuring techniques. This article focuses on the sensory testing of the oesophagus, and methods and concepts used to assess the relation between gastric volumes or tone and upper GI symptoms. It also summarizes the contributions of these techniques towards identifying the components responsible for the generation of upper GI symptoms. PMID- 17280586 TI - Mechanisms of hypersensitivity in IBS and functional disorders. AB - General introduction The concept of visceral hypersensitivity is accepted as being germane to several functional gastrointestinal disorders (FGIDs). The causes or risk factors associated with this hypersensitivity are unclear. This article addresses the proposed mechanisms leading to hypersensitivity: from genetic to inflammatory disorders, from central to peripheral alterations of function. However, in order to place visceral hypersensitivity in a more global perspective as an aetiological factor for FGIDs, it also provides a review of recent evidence regarding the role of other peripheral mechanisms (the intraluminal milieu), as also genetic factors in the pathophysiology of these disorders. The article has been divided into five independent sections. The first three sections summarize the evidence of visceral hypersensitivity as a biological marker of functional gut disorders, the peripheral and central mechanisms involved, and the role of inflammation on hypersensitivity. In opposition to visceral hypersensitivity as an isolated phenomenon in functional gut disorders, the last two sections focus on the importance of peripheral mechanisms, like motor disturbances, specifically those resulting on altered transport of intestinal gas, and alterations of the intraluminal milieu and genetics. PMID- 17280587 TI - Serotonergic and non-serotonergic targets in the pharmacotherapy of visceral hypersensitivity. AB - Visceral hypersensitivity is considered a key mechanism in the pathogenesis of functional gastrointestinal (GI) disorders. Targeting visceral hypersensitivity seems an attractive approach to the development of drugs for functional GI disorders. This review summarizes current knowledge on targets for the treatment of visceral hypersensitivity, and the status of current and future drug and probiotic treatment development, and the role of pharmacogenomic factors. PMID- 17280588 TI - Effective use of microarrays in neuroendocrine research. AB - The development of microarray technology makes it possible to simultaneously assay the expression level of hundreds to tens of thousands of mRNA transcripts in one experiment. Genome-wide transcriptional analysis has increasing importance for many areas of neuroendocrinology research. The expense and technical complexity of microarray experiments can make it difficult to navigate the terrain of rival platforms and technologies. In this review, we provide a practical view and comparison of various microarray technologies. Affymetrix arrays, high-density cDNA arrays, membrane arrays and experimental design and data analysis are all discussed by researchers currently using these techniques to study gene regulation in neuroendocrine tissues. PMID- 17280589 TI - Evidence for increased neuropeptide Y synthesis in mediobasal hypothalamus in relation to parental hyperphagia and gonadal activation in breeding ring doves. AB - Like lactating mammals, male and female ring dove parents increase their food consumption to meet the energetic challenges of provisioning their young. To clarify the neurochemical mechanisms involved, the present study investigated the relationship between parental hyperphagia and changes in activity of the potent orexigen neuropeptide Y (NPY) in the hypothalamus of breeding doves. Changes in NPY-immunoreactive (NPY-ir) cell numbers in the tuberal hypothalamus of male and female doves were examined by immunocytochemistry at six stages of the breeding cycle. Parallel NPY mRNA measurements were recorded in mediobasal hypothalamus (which includes the tuberal hypothalamus) by semiquantitative reverse transcription-polymerase chain reaction using 18S rRNA as the internal standard. NPY mRNA changes were also measured in the mediobasal hypothalamus of nonbreeding doves following intracranial administration of prolactin, an orexigenic hormone that is elevated in the plasma of parent doves, and in response to food deprivation, which mimics the negative energy state that develops in parents as they provision their growing young. NPY-ir cell numbers in the tuberal hypothalamus and NPY mRNA levels in the mediobasal hypothalamus were significantly higher in breeding males and females during the period of parental hyperphagia after hatching than during the late incubation period when food intake remains unchanged. In nonbreeding doves, food deprivation and prolactin treatment increased NPY mRNA in this region by two- to three-fold, which suggests that NPY expression is sensitive to hormonal and metabolic signals associated with parenting. We conclude that NPY synthesis is increased in the mediobasal hypothalamus during the posthatching period, which presumably supports increased NPY release and resulting parental hyperphagia. NPY-ir and mRNA were also high in the mediobasal hypothalamus prior to egg laying when food intake remained unchanged. Several lines of evidence suggest that this elevation in NPY supports the increased gonadal activity that accompanies intense courtship and nest building interactions in breeding doves. PMID- 17280590 TI - Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function in juvenile guinea pigs. AB - The neurodevelopmental consequences of prenatal glucocorticoid exposure are not well-understood, particularly in species that give birth to neuroanatomically mature offspring. In the present study, we hypothesised that repeated prenatal glucocorticoid administration would alter hypothalamo-pituitary-adrenal (HPA) function in juvenile guinea pig offspring. Pregnant guinea pigs were injected with betamethasone (1 mg/kg) or vehicle on gestational days 40, 41, 50, 51, 60 and 61 (six doses). Prenatal glucocorticoid exposure abolished the pituitary adrenal response to maternal separation in juvenile males, but had no effect in female offspring. Indeed, female offspring (vehicle and betamethasone) did not mount a significant HPA response to separation at 10 days of age. Although there were no effects of prenatal glucocorticoid exposure on hippocampal or hypothalamic corticosteroid receptor expression or corticotrophin-releasing factor (CRF) mRNA, there were significant effects in the pituitary and adrenal; again males were more affected than females. Prenatal glucocorticoid exposure increased pituitary pro-opiomelanocortin and CRF receptor mRNA, and markedly decreased adrenocortical CYP17 mRNA. In conclusion, repeated prenatal glucocorticoid exposure has profound influences on HPA function and regulation in the juvenile guinea pig, and this involves altered regulation at the level of the pituitary and adrenal cortex. Furthermore, juvenile males appear to be more vulnerable to the effects of prenatal glucocorticoid exposure than females. PMID- 17280591 TI - Effects of in vivo and in vitro administration of ghrelin, leptin and neuropeptide mediators on pulsatile gonadotrophin-releasing hormone secretion from male rat hypothalamus before and after puberty. AB - The present study aimed to investigate the effects of leptin and ghrelin on pulsatile pulsatile gonadotrophin-releasing hormone (GnRH) secretion in vitro with emphasis on neuropeptide mediators and changes between prepuberty (15 days) and sexual maturity (50 days) in the male rat. When hypothalamic explants were studied 90 min after an intraperitoneal injection of leptin, ghrelin or agouti related protein (AgRP) at 15 days, the GnRH interpulse interval (IPI) was significantly increased by ghrelin and AgRP and decreased by leptin. At 50 days, an increase in GnRH IPI was also caused by ghrelin and AgRP. When the peptides were directly incubated with the explants, the effects of leptin and AgRP in vitro were consistent with those seen after in vivo administration. By contrast, ghrelin resulted in a reduction of GnRH IPI and this was observed at 15 days only. To delineate the neuropeptide mediators of leptin and the effects of ghrelin in the hypothalamus, various hypothalamic neuropeptides and antagonists were used in vitro. At 15 days, the GnRH IPI was significantly decreased after incubation with cocaine and amphetamine-regulated transcript (CART), alpha melanocyte-stimulating hormone, corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY). The reduction of GnRH IPI caused by leptin was partially prevented by either an anti-CART antiserum or SHU 9119, a melanocortin MC3/MC4 receptor antagonist or a CRF receptor antagonist. The NPY-Y5 receptor antagonist did not influence the effects of leptin whereas that antagonist totally prevented the decrease in GnRH IPI caused by ghrelin. The ghrelin-induced reduction of GnRH IPI was partially prevented by SHU 9119. When used alone, SHU 9119 or a CRF receptor antagonist resulted in increased GnRH IPI at 50 days while they had no effects at 15 days. The NPY-Y5 receptor antagonist resulted in increased GnRH IPI at 15 and 50 days. In conclusion, leptin and ghrelin show opposing effects on pulsatile GnRH secretion after administration in vivo whereas they both have stimulatory effects in vitro. Such effects involve consistently the anorectic peptides CART and CRF for leptin that are mainly active at 15 days. The melanocortigenic system appears to mediate the effects of both leptin and ghrelin. The effects of ghrelin also involve NPY receptors and operate effectively before and at sexual maturity. PMID- 17280592 TI - Interaction between oestrogen and oxytocin on hypothalamic-pituitary-adrenal axis activity. AB - In addition to its role in reproduction, oxytocin has central actions modulating behavioural and hypothalamic-pituitary-adrenal (HPA) axis responses during late pregnancy and lactation. The hypothesis that ovarian hormones modulate the effects of oxytocin on HPA axis activity was studied in 7-day ovariectomised rats receiving oestradiol with or without progesterone replacement and intracerebroventricular (i.c.v) minipump infusion of oxytocin (100 ng/h). In an initial experiment, i.c.v. oxytocin had no effect on basal or restraint stimulated plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations or hypothalamic corticotrophin-releasing factor (CRF) mRNA expression with low oestradiol replacement alone but it had a stimulatory effect in the presence of low oestradiol and progesterone. To investigate further whether oestradiol modulates central actions of oxytocin, rats received low dioestrous (low), pro-oestrous (medium) or pregnancy (high) oestradiol replacement levels, yielding plasma concentrations of < 5, 17.3 +/- 4.5 and 258 +/- 32 pg/ml, respectively, with or without i.c.v. oxytocin. Oestradiol caused dose-dependent increases in basal plasma ACTH and corticosterone concentrations but decreased the ACTH response to restraint stress. In parallel to the changes in basal plasma ACTH, high oestrogen increased basal CRF hnRNA, CRF mRNA in the paraventricular nucleus and pro-opiomelanocortin (POMC) mRNA in the pituitary gland, while decreasing restraint stress-stimulated levels. Intracerebroventricular administration of oxytocin reduced basal and stress stimulated plasma ACTH, hypothalamic CRF hnRNA (30 min), CRF mRNA and pituitary POMC mRNA (4 h) levels parallel to the increases induced by elevating plasma oestradiol. The present study demonstrates the converse effects of oestradiol on basal and restraint stress-stimulated basal HPA axis activity, and that the ability of central oxytocin to inhibit HPA axis activity depends on the levels of circulating oestradiol. PMID- 17280593 TI - Intracerebroventricular administration of corticotrophin-releasing hormone receptor antagonists produces different effects on hypothalamic pituitary adrenal responses to novel restraint depending on the stress history of the animal. AB - Corticotrophin-releasing hormone (CRH) regulates acute stress-induced changes in neuroendocrine function and behaviour. However, little is known about CRH functions in animals that have prior experience with repeated stress. Repeatedly stressed rats exhibit a habituated hypothalamic-pituitary-adrenal (HPA) response to a familiar, homotypic stressor but exhibit maintained or enhanced HPA responses to a novel, heterotypic stressor. We examined the effects of intracerebroventricular (i.c.v.) administration of two different nonselective CRH receptor antagonists, alpha-helical CRH(9-41) (ahCRH) or D-Phe CRH(12-41) (D PheCRH), on HPA responses to acute restraint in rats previously exposed to repeated cold stress (i.e. facilitated responses). Antagonists were administered as single i.c.v. injections prior to restraint to provide a general index of CRH function in control versus repeatedly-stressed rats. CRH receptor blockade with either ahCRH or D-PheCRH produced different effects on HPA responses to novel restraint depending on whether the animal had been previously cold stressed or not. Interestingly, some agonist-type effects were observed but only in repeatedly-stressed rats. In summary, these results indicate that manipulations of the CRH receptor have different effects on HPA activity depending on the stress history of the animal. PMID- 17280594 TI - Ghrelin stimulates adrenocorticotrophic hormone (ACTH) secretion by human ACTH secreting pituitary adenomas in vitro. AB - Ghrelin is a brain-gut peptide with wide-ranging endocrine, metabolic, cardiovascular and neural effects. Ghrelin, like its synthetic counterparts, the growth hormone (GH) secretagogues, has been shown to markedly stimulate adrenocorticotrophic hormone (ACTH) and cortisol secretion in humans and the ACTH releasing effect of GH secretagogues is even greater in patients with pituitary ACTH-secreting tumours. Furthermore, these tumours synthesize ghrelin itself, suggesting an intrapituitary ghrelin circuit. The aim of the present study was to evaluate the effect of ghrelin on ACTH secretion by human pituitary corticotroph tumours in vitro to test the functionality of this circuit. Nine ACTH-secreting pituitary tumours (four microadenomas, five macroadenomas) were collected during surgery and incubated with 10-100 nM human ghrelin or with 10 nM human corticotrophin-releasing hormone (CRH). Control experiments were performed in rat anterior pituitary primary cultures. ACTH secretion was assessed after 4 h and 24 h incubation by immunometric assay. After 4 h of incubation with ghrelin, medium ACTH concentrations were two- to ten-fold higher compared to ACTH concentrations in unstimulated wells. The ACTH-releasing effect of ghrelin was significantly less than the response elicited by 10 nM CRH (up to 40-fold) Similar results were obtained after 24 h of incubation and a superimposable response pattern was observed in rat anterior pituitary primary cultures. The present study demonstrates that the endogenous GH secretagogue, ghrelin, stimulates ACTH secretion directly from human tumoural corticotrophs, as well as from normal rat pituitary, and indicates that the marked ACTH release elicited by ghrelin in patients with Cushing's disease in vivo is due, at least in part, to its action on the pituitary tumour. However, the reversal of the response pattern reported in vivo, with ghrelin proving a lesser stimulant than CRH in vitro, suggests that additional, suprapituitary mechanisms are involved in the in vivo response. Moreover, these data uphold the concept of a functional intratumoural ghrelin paracrine circuit in human corticotroph adenomas. PMID- 17280595 TI - Neuroendocrinological mechanisms of actions of antidepressant drugs. AB - Noradrenaline or serotonin (5-HT) reuptake-inhibiting antidepressants such as reboxetine or citalopram acutely stimulate cortisol and adrenocorticotrophic hormone (ACTH) secretion in healthy volunteers, whereas mirtazapine acutely inhibits the ACTH and cortisol release, probably due to its antagonism at central 5-HT(2) and/or H(1) receptors. These differential effects of antidepressants on cortisol and ACTH secretion in healthy subjects after single administration are also reflected by their different time course in the down-regulation of hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity in depressed patients as assessed by serial dexamethasone (DEX)/corticotrophin-releasing hormone (CRH) tests: Reuptake-inhibiting antidepressants such as reboxetine gradually normalise HPA axis hyperactivity in depressed patients during several weeks of treatment via up-regulation of mineralocorticoid and glucocorticoid receptor function and by step-by-step restoration of the disturbed feedback control. By contrast, mirtazapine markedly reduces HPA axis activity in depressed patients within 1 week, but there is a partial re-enhancement of HPA hormone secretion after several weeks of therapy. In all studies performed to date, the short-term effects of daily treatment with antidepressants on the DEX/CRH test results are comparable in responders and nonresponders. Moreover, a reduction in HPA axis activity is not necessarily followed by a favourable clinical response and some depressed patients keep on showing nonsuppression in the DEX/CRH test despite clinical improvement. Therefore, the importance of HPA axis dysregulation for the short-term efficacy of antidepressants continues to be a matter of debate. However, there are convincing data suggesting that persisting nonsuppression in the DEX/CRH test despite clinical remission predicts an enhanced risk for relapse of depressive symptomatology with respect to the medium and long-term outcome. PMID- 17280596 TI - Abstracts of the Urological Society of Australia and New Zealand, 60th Annual Scientific Meeting 2007, Adelaide, SA, Australia, 18-22 February 2007. PMID- 17280598 TI - Case studies in breakthrough pain. AB - OBJECTIVE: To illustrate the variable presentations of and treatments for breakthrough pain (BTP). DESIGN: Five cases of BTP were selected by the author, and treatment options were then considered. RESULTS: Breakthrough pain presents in many different ways in clinical practice. Clinicians must first evaluate patients to identify the subtype, etiology, severity, and pattern of BTP, and then use that information to suggest appropriate interventions. Whenever possible, correctable causes of BTP should first be addressed. A variety of treatment tools are available, including opioid analgesics, nonopioid analgesics, adjuvant agents, nonpharmacologic strategies, and procedural and surgical interventions. In many cases, more than one treatment option will be appropriate, but in all cases, regular communication between patient and clinician will be needed to achieve optimal control of BTP. CONCLUSION: Treatment of BTP should be individualized by using a multidisciplinary approach to address each patient's pain profile. PMID- 17280600 TI - Recognition and diagnosis of breakthrough pain. AB - OBJECTIVE: To review major clinical issues related to recognition and diagnosis of breakthrough pain. ISSUES: Persistent pain and breakthrough pain (BTP) are distinct clinical entities that should be recognized, diagnosed, and treated individually. BTP is common in patients with cancer and a variety of other chronic diseases. Reported incidence of BTP varies widely from 16% to 95% of those with persistent pain syndromes. Such variability is likely due to lack of a clear consensus on the definition of BTP. It is most commonly defined as an abrupt, short-lived, and intense pain that "breaks through" the around-the-clock analgesia that controls persistent pain. The three subtypes of BTP are incident, idiopathic, and end-of-dose failure. BTP also is categorized as somatic, visceral, neuropathic, or mixed. Appropriate assessment of the patient takes into consideration source, severity, pattern, subtype, and cause of pain. Successful treatment is important because BTP has a profound impact on the patient's quality of life, as well as cost of health care. BTP is likely to be underdiagnosed and undertreated because of the lack of consensus on its definition and unwarranted concerns among health care professionals and patients about overmedicating. Additionally, and for reasons not entirely clear, many physicians and other health care providers place a low priority on pain management and underrecognize the occurrence of BTP in patients with persistent pain. CONCLUSION: Greater knowledge and awareness of BTP in cancer and nonmalignant conditions will lead to improved recognition and diagnosis of BTP and ultimately to more effective treatment and enhanced quality of life for these patients. PMID- 17280601 TI - The treatment of breakthrough pain. AB - OBJECTIVE: To review strategies for treating patients with breakthrough pain (BTP). DESIGN: This review is based on expert consensus recommendations for treating BTP and is supplemented by recent clinical studies and the author's clinical experience. RESULTS: Breakthrough pain is severe or excruciating pain of rapid onset that can disable or even immobilize the patient. Patients with BTP should be assessed after baseline persistent pain has been stabilized with around the-clock (ATC) analgesics. Clues about the cause and pattern of BTP may be identified from a patient history, preferably including a pain diary. Effective treatment can greatly improve the patient's quality of life and should be tailored for each patient, taking into consideration the cause and type of the BTP episodes. Short-acting opioid analgesics are the primary treatment. The absorption characteristics, onset of action, and duration of effect vary among the available opioid compounds based on their lipophilicity. The dose and/or dosing frequency of the ATC analgesic should be adjusted for patients with end-of dose BTP. Short-acting oral opioids are useful when given preemptively in patients with predictable incident BTP, while rapid-onset transmucosal lipophilic opioids are most effective for patients with unpredictable incident or idiopathic BTP. Regardless of the subtype of BTP, nonpharmacologic strategies are often helpful in alleviating pain and anxiety and should be used to supplement pharmacologic intervention for BTP. CONCLUSION: Breakthrough pain can often be successfully treated by tailoring opioid therapy based on the subtype of BTP. These characteristics of BTP will determine the most appropriate opioid compound (i.e., hydrophilic vs lipophilic) and most effective mode of drug delivery. PMID- 17280602 TI - Perioperative complications in infant cleft repair. AB - BACKGROUND: Cleft surgery in infants includes special risks due to the kind of the malformation. These risks can be attributed in part to the age and the weight of the patient. Whereas a lot of studies investigated the long-term facial outcome of cleft surgery depending on the age at operation, less is known about the complications arising during a cleft surgery in early infancy. METHODS: We investigated the incidence and severity of perioperative complications in 174 infants undergoing primary cleft surgery. The severity and the complications were recorded during the intraoperative and the early postoperative period according to the classification by Cohen. RESULTS: Our study revealed that minor complications occurred in 50 patients. Severe complications were observed during 13 operations. There was no fatal complication in the perioperative period. The risk of complications was found to be directly correlated to the body weight at the time of the surgery. Most of the problems appeared intraoperatively, but they were also followed by complications immediately after the extubation. CONCLUSION: In conclusion, cleft surgery in infancy is accompanied by frequent and sometimes severe perioperative complications that may be attributed to this special surgical field. PMID- 17280603 TI - Caspase-mediated cleavage of the exosome subunit PM/Scl-75 during apoptosis. AB - Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive systemic autoimmunity in susceptible hosts. A number of subunits of the exosome, a complex of 3'-->5' exoribonucleases that functions in a variety of cellular processes, are recognized by the so-called anti-PM/Scl autoantibodies, found predominantly in patients suffering from an overlap syndrome of myositis and scleroderma. Here we show that one of these subunits, PM/Scl-75, is cleaved during apoptosis. PM/Scl 75 cleavage is inhibited by several different caspase inhibitors. The analysis of PM/Scl-75 cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by caspase-8, and relatively inefficiently by caspase-3 and caspase-7. Cleavage of the PM/Scl-75 protein occurs in the C-terminal part of the protein at Asp369 (IILD369 [see text] G), and at least a fraction of the resulting N-terminal fragments of PM/Scl 75 remains associated with the exosome. Finally, the implications of PM/Scl-75 cleavage for exosome function and the generation of anti-PM/Scl-75 autoantibodies are discussed. PMID- 17280604 TI - Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D. AB - BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr/Thr 11 form of SP-D is associated with low serum levels and assembles predominantly as trimers as opposed to the more common multimeric forms of SP-D. METHODS: Preliminary experiments were done to establish the effects of different monoclonal antibodies against SP-D on ability of SP-D to bind to or neutralize the virus. We then purified natural human trimeric and multimeric forms of SP-D from amniotic fluid and tested ability of these preparations to bind to IAV, to inhibit infectivity and hemagglutination activity of IAV in vitro. RESULTS: In initial experiments mAbs directed against different areas on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs) in viral neutralization assays as compared to multimeric SP-D. CONCLUSION: These studies indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP-D can be useful for dissecting out different functional properties of the protein. PMID- 17280605 TI - Integrative analysis of a cancer somatic mutome. AB - BACKGROUND: The consecutive acquisition of genetic alterations characterizes neoplastic processes. As a consequence of these alterations, molecular interactions are reprogrammed in the context of highly connected and regulated cellular networks. The recent identification of the collection of somatically mutated genes in breast tumors (breast cancer somatic "mutome") allows the comprehensive study of its function and organization in complex networks. RESULTS: We analyzed functional genomic data (loss of heterozygosity, copy number variation and gene expression in breast tumors) and protein binary interactions from public repositories to identify potential novel components of neoplastic processes, the functional relationships between them, and to examine their coordinated function in breast cancer pathogenesis. This analysis identified candidate tumor suppressors and oncogenes, and new genes whose expression level predicts survival rate in breast cancer patients. Mutome network modeling using different types of pathological and healthy functional relationships unveils functional modules significantly enriched in genes or proteins (genes/proteins) with related biological process Gene Ontology terms and containing known breast cancer-related genes/proteins. CONCLUSION: This study presents a comprehensive analysis of the breast somatic mutome, highlighting those genes with a higher probability of playing a determinant role in tumorigenesis and better defining molecular interactions related to the neoplastic process. PMID- 17280606 TI - Predicting zinc binding at the proteome level. AB - BACKGROUND: Metalloproteins are proteins capable of binding one or more metal ions, which may be required for their biological function, for regulation of their activities or for structural purposes. Metal-binding properties remain difficult to predict as well as to investigate experimentally at the whole proteome level. Consequently, the current knowledge about metalloproteins is only partial. RESULTS: The present work reports on the development of a machine learning method for the prediction of the zinc-binding state of pairs of nearby amino-acids, using predictors based on support vector machines. The predictor was trained using chains containing zinc-binding sites and non-metalloproteins in order to provide positive and negative examples. Results based on strong non redundancy tests prove that (1) zinc-binding residues can be predicted and (2) modelling the correlation between the binding state of nearby residues significantly improves performance. The trained predictor was then applied to the human proteome. The present results were in good agreement with the outcomes of previous, highly manually curated, efforts for the identification of human zinc binding proteins. Some unprecedented zinc-binding sites could be identified, and were further validated through structural modelling. The software implementing the predictor is freely available at: http://zincfinder.dsi.unifi.it CONCLUSION: The proposed approach constitutes a highly automated tool for the identification of metalloproteins, which provides results of comparable quality with respect to highly manually refined predictions. The ability to model correlations between pairwise residues allows it to obtain a significant improvement over standard 1D based approaches. In addition, the method permits the identification of unprecedented metal sites, providing important hints for the work of experimentalists. PMID- 17280607 TI - Quantifying the natural history of post-radical prostatectomy incontinence using objective pad test data. AB - BACKGROUND: Urinary incontinence (UI) following radical prostatectomy is a well recognized risk of the surgery. In most patients post-operative UI improves over time. To date, there is limited objective, quantitative data on the natural history of the resolution of post-prostatectomy UI. The purpose of this study was to define the natural history of post radical prostatectomy incontinence using an objective quantitative tool, the 1-hour standard pad test. METHODS: 203 consecutive patients underwent radical prostatectomy by a single surgeon between 03/98 & 08/03. A standardized 1-hour pad test was administered at subsequent postoperative clinic visits. The gram weight of urine loss was recorded and subdivided into four groups defined according to the grams of urine loss: minimal (<1 g), mild (>1, <10 g), moderate (10-50 g) and severe (>50 g). Patients were evaluated: at 2 weeks (catheter removal), 6 weeks, 18 weeks, 30 weeks, 42 weeks and 54 weeks. The data set was analyzed for average urine loss as well as grams of urine loss at each time point, the percentage of patients and the distribution of patients in each category. RESULTS: Mean follow up was 118 weeks. The majority of patients experienced incontinence immediately after catheter removal at 2 weeks that gradually improved with time. While continued improvement was noted to 1 year, most patients who achieved continence did so by 18 weeks post-op. CONCLUSION: While the majority of patients experience mild to severe UI immediately following catheter removal, there is a rapid decrease in leaked weight during the first 18 weeks following RRP. Patients continue to improve out to 1 year with greater than 90% having minimal leakage by International Continence Society criteria. PMID- 17280608 TI - Comparison of the xylose reductase-xylitol dehydrogenase and the xylose isomerase pathways for xylose fermentation by recombinant Saccharomyces cerevisiae. AB - BACKGROUND: Two heterologous pathways have been used to construct recombinant xylose-fermenting Saccharomyces cerevisiae strains: i) the xylose reductase (XR) and xylitol dehydrogenase (XDH) pathway and ii) the xylose isomerase (XI) pathway. In the present study, the Pichia stipitis XR-XDH pathway and the Piromyces XI pathway were compared in an isogenic strain background, using a laboratory host strain with genetic modifications known to improve xylose fermentation (overexpressed xylulokinase, overexpressed non-oxidative pentose phosphate pathway and deletion of the aldose reductase gene GRE3). The two isogenic strains and the industrial xylose-fermenting strain TMB 3400 were studied regarding their xylose fermentation capacity in defined mineral medium and in undetoxified lignocellulosic hydrolysate. RESULTS: In defined mineral medium, the xylose consumption rate, the specific ethanol productivity, and the final ethanol concentration were significantly higher in the XR- and XDH-carrying strain, whereas the highest ethanol yield was achieved with the strain carrying XI. While the laboratory strains only fermented a minor fraction of glucose in the undetoxified lignocellulose hydrolysate, the industrial strain TMB 3400 fermented nearly all the sugar available. Xylitol was formed by the XR-XDH carrying strains only in mineral medium, whereas in lignocellulose hydrolysate no xylitol formation was detected. CONCLUSION: Despite by-product formation, the XR XDH xylose utilization pathway resulted in faster ethanol production than using the best presently reported XI pathway in the strain background investigated. The need for robust industrial yeast strains for fermentation of undetoxified spruce hydrolysates was also confirmed. PMID- 17280609 TI - Molecular epidemiology of measles viruses in China, 1995-2003. AB - This report describes the genetic characterization of 297 wild-type measles viruses that were isolated in 24 provinces of China between 1995 and 2003. Phylogenetic analysis of the N gene sequences showed that all of the isolates belonged to genotype H1 except 3 isolates, which were genotype A. The nucleotide sequence and predicted amino acid homologies of the 294-genotype H1 strains were 94.7%-100% and 93.3%-100%, respectively. The genotype H1 isolates were divided into 2 clusters, which differed by approximately 2.9% at the nucleotide level. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Even though other measles genotypes have been detected in countries that border China, this report shows that genotype H1 is widely distributed throughout the country and that China has a single, endemic genotype. This important baseline data will help to monitor the progress of measles control in China. PMID- 17280610 TI - Factor interaction analysis for chromosome 8 and DNA methylation alterations highlights innate immune response suppression and cytoskeletal changes in prostate cancer. AB - BACKGROUND: Alterations of chromosome 8 and hypomethylation of LINE-1 retrotransposons are common alterations in advanced prostate carcinoma. In a former study including many metastatic cases, they strongly correlated with each other. To elucidate a possible interaction between the two alterations, we investigated their relationship in less advanced prostate cancers. RESULTS: In 50 primary tumor tissues, no correlation was observed between chromosome 8 alterations determined by comparative genomic hybridization and LINE-1 hypomethylation measured by Southern blot hybridization. The discrepancy towards the former study, which had been dominated by advanced stage cases, suggests that both alterations converge and interact during prostate cancer progression. Therefore, interaction analysis was performed on microarray-based expression profiles of cancers harboring both alterations, only one, or none. Application of a novel bioinformatic method identified Gene Ontology (GO) groups related to innate immunity, cytoskeletal organization and cell adhesion as common targets of both alterations. Many genes targeted by their interaction were involved in type I and II interferon signaling and several were functionally related to hereditary prostate cancer genes. In addition, the interaction appeared to influence a switch in the expression pattern of EPB41L genes encoding 4.1 cytoskeleton proteins. Real-time RT-PCR revealed GADD45A, MX1, EPB41L3/DAL1, and FBLN1 as generally downregulated in prostate cancer, whereas HOXB13 and EPB41L4B were upregulated. TLR3 was downregulated in a subset of the cases and associated with recurrence. Downregulation of EPB41L3, but not of GADD45A, was associated with promoter hypermethylation, which was detected in 79% of carcinoma samples. CONCLUSION: Alterations of chromosome 8 and DNA hypomethylation in prostate cancer probably do not cause each other, but converge during progression. The present analysis implicates their interaction in innate immune response suppression and cytoskeletal changes during prostate cancer progression. The study thus highlights novel mechanisms in prostate cancer progression and identifies novel candidate genes for diagnostic and therapeutic purposes. In particular, TLR3 expression might be useful for prostate cancer prognosis and EPB41L3 hypermethylation for its detection. PMID- 17280611 TI - Prevalence and associated factors of viral hepatitis and transferrin elevations in 5036 patients admitted to the emergency room of a Swiss university hospital: cross-sectional study. AB - BACKGROUND: The epidemiology of liver disease in patients admitted to emergency rooms is largely unknown. The current study aimed to measure the prevalence of viral hepatitis B and C infection and pathological laboratory values of liver disease in such a population, and to study factors associated with these measurements. METHODS: Cross-sectional study in patients admitted to the emergency room of a university hospital. No formal exclusion criteria. Determination of anti-HBs, anti-HCV, transferrin saturation, alanine aminotransferase, and obtaining answers from a study-specific questionnaire. RESULTS: The study included 5'036 patients, representing a 14.9% sample of the target population during the study period. Prevalence of anti-HBc and anti-HCV was 6.7% (95%CI 6.0% to 7.4%) and 2.7% (2.3% to 3.2%), respectively. Factors independently associated with positive anti-HBc were intravenous drug abuse (OR 18.3; 11.3 to 29.7), foreign country of birth (3.4; 2.6 to 4.4), non-white ethnicity (2.7; 1.9 to 3.8) and age > or =60 (2.0; 1.5 to 2.8). Positive anti-HCV was associated with intravenous drug abuse (78.9; 43.4 to 143.6), blood transfusion (1.7; 1.1 to 2.8) and abdominal pain (2.7; 1.5 to 4.8). 75% of all participants were not vaccinated against hepatitis B or did not know their vaccination status. Among anti-HCV positive patients only 49% knew about their infection and 51% reported regular alcohol consumption. Transferrin saturation was elevated in 3.3% and was associated with fatigue (prevalence ratio 1.9; 1.2 to 2.8). CONCLUSION: Emergency rooms should be considered as targets for public health programs that encourage vaccination, patient education and screening of high-risk patients for liver disease with subsequent referral for treatment if indicated. PMID- 17280613 TI - Sporadic renal cell carcinoma in young and elderly patients: are there different clinicopathological features and disease specific survival rates? AB - BACKGROUND: Sporadic renal cell carcinoma (RCC) is rare in young adults. In the present retrospective study we reviewed clinicopathological features and disease specific survival rates in young patients (<= 45 years) with RCC and compared them to old patients (>= 75 years) with RCC. METHODS: Between 1992 and 2005 a total of 1042 patients were treated for RCC at our institution. We found 70 patients 45 years or younger (YP) and 150 patients 75 years or older (OP) at time of diagnosis. There were no differences in therapeutical approaches between both groups. Clinical and biologic parameters at diagnosis were compared and subjected to uni- and multivariate analysis to study cancer specific survival and progression rate. Mean postoperative follow-up in both groups was 50.1 months. RESULTS: Mean age was 39 years in YP and 80 years in OP, respectively. YP demonstrated significantly lower stage (pT1-pT2 N0 M0, p = 0.03), lower tumor grade (p = 0.01) and higher male-to-female ratio (p < 0.001). The rate of lymph node metastases or distant metastatic disease at presentation did not differ significantly between both groups. In multivariate analysis young age was independently associated with a higher 5-year cancer specific survival (95.2% vs. 72.3%, p = 0.009) and a lower 5-year progression rate (11.3% vs. 42.5%, p = 0.002). CONCLUSION: Sporadic RCC in young patients have lower tumor stages and grades and a better outcome compared to elderly. Age <= 45 years was an independent prognostic factor for survival and progression. PMID- 17280612 TI - Elastofibroma dorsi--differential diagnosis in chest wall tumours. AB - BACKGROUND: Elastofibromas are benign soft tissue tumours mostly of the infrascapular region between the thoracic wall, the serratus anterior and the latissimus dorsi muscle with a prevalence of up to 24% in the elderly. The pathogenesis of the lesion is still unclear, but repetitive microtrauma by friction between the scapula and the thoracic wall may cause the reactive hyperproliferation of fibroelastic tissue. METHODS: We present a series of seven cases with elastofibroma dorsi with reference to clinical findings, further clinical course and functional results after resection, as well as recurrence. Data were obtained retrospectively by clinical examination, phone calls to the patients' general practitioners and charts review. Follow-up time ranged from four months to nine years and averaged 53 months. RESULTS: The patients presented with swelling of the infrascapular region or snapping scapula. In three cases, the lesion was painful. The ratio men/women was 2/5 with a mean age of 64 years. The tumor sizes ranged from 3 to 13 cm. The typical macroscopic aspect was characterized as poorly defined fibroelastic soft tissue lesion with a white and yellow cut surface caused by intermingled remnants of fatty tissue. Microscopically, the lesions consisted of broad collagenous strands and densely packed enlarged and fragmented elastic fibres with mostly round shapes. In all patients but one, postoperative seroma (which had to be punctuated) occurred after resection; however, at follow-up time, no patient reported any decrease of function or sensation at the shoulder or the arm of the operated side. None of the patients experienced a relapse. CONCLUSION: In differential diagnosis of soft tissue tumors located at this specific site, elastofibroma should be considered as likely diagnosis. Due to its benign behaviour, the tumor should be resected only in symptomatic patients. PMID- 17280614 TI - Expression and localization of estrogenic type 12 17beta-hydroxysteroid dehydrogenase in the cynomolgus monkey. AB - BACKGROUND: We have recently discovered that human type 12 17beta-HSD (h17beta HSD12), a homolog of type 3 17beta-HSD, is a new estrogen-specific 17beta hydroxysteroid dehydrogenase involved in the production of estradiol (E2). To further characterize this estradiol-producing enzyme, we have isolated the corresponding cDNA in the cynomolgus monkey (Macaca fascicularis), characterized its enzymatic activities and performed cellular localization using in situ hybridization. RESULTS: Using HEK-293 cells stably expressing Macaca fascicularis type 12 17beta-HSD (mf17beta-HSD12), we have found that the mf17beta-HSD12 catalyzes efficiently and selectively the transformation of El into E2, in analogy with the h17beta-HSD12. We have also quantified the mf17beta-HSD12 mRNA expression levels in a series of Macaca fascicularis tissues using Quantitative RealTime PCR. The Macaca fascicularis 17beta-HSD12 mRNA is widely expressed with the highest levels tissues found in the cerebellum, spleen and adrenal with moderate level observed in all the other examined, namely the testis, ovary, cerebral cortex, liver, heart, prostate, mammary gland, myometrium, endometrium, skin, muscle and pancreas. To gain knowledge about the cellular localization of the mf17beta-HSD12 mRNA expression, we performed in situ hybridization using a 35S-labeled cRNA probe. Strong labeling was observed in epithelial cells and stromal cells of the mammary gland. In the uterus, the labeling is detected in epithelial cells and stromal cells of the endometrium. CONCLUSION: These results strongly suggest that the Macaca fascicularis 17beta-HSD12 is an essential partner of aromatase in the biosynthesis of estradiol (E2). It strongly suggests that in the estradiol biosynthesis pathway, the step of 17-ketoreduction comes after the step of the aromatization (the aromatization of 4-androstendione to estrone followed by the conversion of estrone into estradiol by estrogen specific l7beta-HSDs) which is in contrast with the hypothesis suggesting that 4 androstenedione is converted to testosterone followed by the aromatization of testosterone. PMID- 17280615 TI - NeuroTerrain--a client-server system for browsing 3D biomedical image data sets. AB - BACKGROUND: Three dimensional biomedical image sets are becoming ubiquitous, along with the canonical atlases providing the necessary spatial context for analysis. To make full use of these 3D image sets, one must be able to present views for 2D display, either surface renderings or 2D cross-sections through the data. Typical display software is limited to presentations along one of the three orthogonal anatomical axes (coronal, horizontal, or sagittal). However, data sets precisely oriented along the major axes are rare. To make fullest use of these datasets, one must reasonably match the atlas' orientation; this involves resampling the atlas in planes matched to the data set. Traditionally, this requires the atlas and browser reside on the user's desktop; unfortunately, in addition to being monolithic programs, these tools often require substantial local resources. In this article, we describe a network-capable, client-server framework to slice and visualize 3D atlases at off-axis angles, along with an open client architecture and development kit to support integration into complex data analysis environments. RESULTS: Here we describe the basic architecture of a client-server 3D visualization system, consisting of a thin Java client built on a development kit, and a computationally robust, high-performance server written in ANSI C++. The Java client components (NetOStat) support arbitrary-angle viewing and run on readily available desktop computers running Mac OS X, Windows XP, or Linux as a downloadable Java Application. Using the NeuroTerrain Software Development Kit (NT-SDK), sophisticated atlas browsing can be added to any Java compatible application requiring as little as 50 lines of Java glue code, thus making it eminently re-useable and much more accessible to programmers building more complex, biomedical data analysis tools. The NT-SDK separates the interactive GUI components from the server control and monitoring, so as to support development of non-interactive applications. The server implementation takes full advantage of data center's high-performance hardware, where it can be co-localized with centrally-located, 3D dataset repositories, extending access to the researcher community throughout the Internet. CONCLUSION: The combination of an optimized server and modular, platform-independent client provides an ideal environment for viewing complex 3D biomedical datasets, taking full advantage of high-performance servers to prepare images and subsets of associated meta-data for viewing, as well as the graphical capabilities in Java to actually display the data. PMID- 17280616 TI - Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl 2 family. AB - INTRODUCTION: Cancer therapies directed at specific molecular targets in signaling pathways of cancer cells, such as tamoxifen, aromatase inhibitors and trastuzumab, have proven useful for treatment of advanced breast cancers. However, increased risk of endometrial cancer with long-term tamoxifen administration and of bone fracture due to osteoporosis in postmenopausal women undergoing aromatase inhibitor therapy are recognized side effects. These side effects as well as drug resistance make it necessary to search for novel molecular targets for drugs on the basis of well-characterized mechanisms of action. METHODS: Using accurate genome-wide expression profiles of breast cancers, we found maternal embryonic leucine-zipper kinase (MELK) to be significantly overexpressed in the great majority of breast cancer cells. To assess whether MELK has a role in mammary carcinogenesis, we knocked down the expression of endogenous MELK in breast cancer cell lines using mammalian vector based RNA interference. Furthermore, we identified a long isoform of Bcl-G (Bcl GL), a pro-apoptotic member of the Bcl-2 family, as a possible substrate for MELK by pull-down assay with recombinant wild-type and kinase-dead MELK. Finally, we performed TUNEL assays and FACS analysis, measuring proportions of apoptotic cells, to investigate whether MELK is involved in the apoptosis cascade through the Bcl-GL-related pathway. RESULTS: Northern blot analyses on multiple human tissues and cancer cell lines demonstrated that MELK was overexpressed at a significantly high level in a great majority of breast cancers and cell lines, but was not expressed in normal vital organs (heart, liver, lung and kidney). Suppression of MELK expression by small interfering RNA significantly inhibited growth of human breast cancer cells. We also found that MELK physically interacted with Bcl-GL through its amino-terminal region. Immunocomplex kinase assay showed that Bcl-GL was specifically phosphorylated by MELK in vitro. TUNEL assays and FACS analysis revealed that overexpression of wild-type MELK suppressed Bcl-GL-induced apoptosis, while that of D150A-MELK did not. CONCLUSION: Our findings suggest that the kinase activity of MELK is likely to affect mammary carcinogenesis through inhibition of the pro-apoptotic function of Bcl-GL. The kinase activity of MELK could be a promising molecular target for development of therapy for patients with breast cancers. PMID- 17280617 TI - Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338). AB - BACKGROUND: The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied. RESULTS: There were few primary PI associated mutations in this PI-naive population, but 84% had NRTI mutations--codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). CONCLUSION: No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen. PMID- 17280618 TI - Immunostimulation and immunoinhibition of premalignant lesions. AB - BACKGROUND: The immune reaction may be either stimulatory or inhibitory to tumor growth, depending upon the local ratio of immune reactants to tumor cells. HYPOTHESIS: A tumor-stimulatory immune response may be essential for survival of a neoplasm in vivo and for the biological progression from a premalignant lesion to a malignancy. Neither a positive nor a negative correlation between the magnitude of an immune-cell infiltrate and a cancer's prognosis can reveal whether the infiltrate was stimulating or inhibiting to the tumor's growth unless the position on the nonlinear curve that relates tumor growth to the magnitude of the immune reaction is known. DISCUSSION: This hypothesis is discussed in relation to the development of human malignant melanomas and colorectal cancers. PMID- 17280619 TI - Stealing the spotlight: CUL4-DDB1 ubiquitin ligase docks WD40-repeat proteins to destroy. AB - Recent investigation of Cullin 4 (CUL4) has ushered this class of multiprotein ubiquitin E3 ligases to center stage as critical regulators of diverse processes including cell cycle regulation, developmental patterning, DNA replication, DNA damage and repair, and epigenetic control of gene expression. CUL4 associates with DNA Damage Binding protein 1 (DDB1) to assemble an ubiquitin E3 ligase that targets protein substrates for ubiquitin-dependent proteolysis. CUL4 ligase activity is also regulated by the covalent attachment of the ubiquitin-like protein NEDD8 to CUL4, or neddylation, and the COP9 signalosome complex (CSN) that removes this important modification. Recently, multiple WD40-repeat proteins (WDR) were found to interact with DDB1 and serve as the substrate-recognition subunits of the CUL4-DDB1 ubiquitin ligase. As more than 150-300 WDR proteins exist in the human genome, these findings impact a wide array of biological processes through CUL4 ligase-mediated proteolysis. Here, we review the recent progress in understanding the mechanism of CUL4 ubiquitin E3 ligase and discuss the architecture of CUL4-assembled E3 ubiquitin ligase complexes by comparison to CUL1-based E3s (SCF). Then, we will review several examples to highlight the critical roles of CUL4 ubiquitin ligase in genome stability, cell cycle regulation, and histone lysine methylation. Together, these studies provide insights into the mechanism of this novel ubiquitin ligase in the regulation of important biological processes. PMID- 17280620 TI - CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden. AB - BACKGROUND: Polymorphisms in and around the CTLA-4 gene have previously been associated to T1D and AITD in several populations. One such single nucleotide polymorphism (SNP), CT60, has been reported to affect the expression level ratio of the soluble (sCTLA-4) to full length CTLA-4 (flCTLA-4) isoforms. The aims of our study were to replicate the association previously published by Ueda et al. of polymorphisms in the CTLA-4 region to T1D and AITD and to determine whether the CT60 polymorphism affects the expression level ratio of sCTLA-4/flCTLA-4 in our population. METHODS: Three SNPs were genotyped in 253 cases (104 AITD cases and 149 T1D cases) and 865 ethnically matched controls. Blood from 23 healthy individuals was used to quantify mRNA expression of CTLA-4 isoforms in CD4+ cells using real-time PCR. Serum from 102 cases and 59 healthy individuals was used to determine the level of sCTLA-4 protein. RESULTS: Here we show association of the MH30, CT60 and JO31 polymorphisms to T1D and AITD in northern Sweden. We also observed a higher frequency of the CT60 disease susceptible allele in our controls compared to the British, Italian and Dutch populations, which might contribute to the high frequency of T1D in Sweden. In contrast to previously published findings, however, we were unable to find differences in the sCTLA 4/flCTLA-4 expression ratio based on the CT60 genotype in 23 healthy volunteers, also from northern Sweden. Analysis of sCTLA-4 protein levels in serum showed no correlation between sCTLA-4 protein levels and disease status or CT60 genotype. CONCLUSION: Association was found between T1D/AITD and all three polymorphisms investigated. However, in contrast to previous investigations, sCTLA-4 RNA and protein expression levels did not differ based on CT60 genotype. Our results do not rule out the CT60 SNP as an important polymorphism in the development of T1D or AITD, but suggest that further investigations are necessary to elucidate the effect of the CTLA-4 region on the development of T1D and AITD. PMID- 17280621 TI - Does preoperative mechanical ventilation affect outcomes in neonates undergoing cardiac surgery? AB - OBJECTIVE: To review, in retrospective fashion, the effect of preoperative mechanical ventilation on neonatal outcomes after cardiac surgery. METHODS: We studied 114 newborns less than 15 days old admitted to the cardiac intensive care unit for cardiac surgery. Of the newborns, 71 (62%) were mechanically ventilated at the referring hospital before transport to our institution. Of the 71 ventilated patients, 14 were extubated and breathing spontaneously before cardiac surgery. We compared variable haemodynamics and outcomes between the 57 patients mechanically ventilated at time of cardiac surgery, and the 57 patients breathing spontaneously at this time. RESULTS: Newborns mechanically ventilated before cardiac surgery had increased preoperative haemodynamic compromise, increased postoperative sepsis (p equal to 0.02) and mortality (p equal to 0.005) compared with those breathing spontaneously before cardiac surgery. CONCLUSION: Newborns requiring preoperative mechanical ventilation had greater risk of postoperative morbidity and mortality. Heightened vigilance is warranted in this population of patients at high risk. PMID- 17280622 TI - The clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fragility fractures in postmenopausal women. AB - OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fractures in postmenopausal women, at different levels of absolute fracture risk. This considers secondary prevention in women who have sustained a previous fracture and primary prevention in those women without a previous fracture, as women with osteoporosis are asymptomatic until a fracture is sustained. DATA SOURCES: Major electronic bibliographic databases were searched in September 2004 and updated in March 2005. REVIEW METHODS: A systematic review was carried out to determine clinical effectiveness using the major electronic bibliographic databases and handsearching reference lists of relevant articles and sponsor submissions. Data from selected studies were assessed and included in the meta-analyses, if appropriate. The model used to calculate cost-effectiveness ratios was an updated version of Sheffield Health Economic Model for Osteoporosis that was populated with absolute risk of fractures using an algorithm being developed for the World Health Organization and supplied in confidence to the authors. The model calculated the number of fractures that occur and provided as output data the costs associated with osteoporotic fractures, and the quality adjusted life-years (QALYs) accrued by a cohort of 100 osteoporotic women, with each fracture being detrimental to health and incurring a cost. When the costs of the intervention were included, the incremental cost compared with no treatment was calculated and divided by the gain in QALYs to calculate cost-effectiveness measures. Treatment with strontium ranelate was calculated against a no-treatment option to evaluate whether it could be given cost-effectively. An incremental analysis against alendronate was also conducted to estimate the cost-effectiveness of strontium ranelate relative to a current standard treatment. The cost-effectiveness of strategies for identifying and treating women without a prior fracture used the risk of fracture as an input to the cost-effectiveness model. RESULTS: Three trials were identified. Pooled data from two studies indicate that strontium ranelate therapy is associated with a reduction in the risk of vertebral fracture [relative risk (RR) compared with placebo 0.60, 95% confidence interval (CI) 0.53 to 0.69, p < 0.001] and non-vertebral fracture (RR 0.84, 95% CI 0.73 to 0.97, p = 0.01). In general, strontium ranelate therapy did not seem to be associated with an increased risk of adverse events. However, the risk of one rare but serious adverse event, venous thromboembolism (including pulmonary embolism), was found to be significantly higher in patients receiving strontium ranelate compared with placebo (RR 1.42, 95% CI 1.02 to 1.98, p = 0.036). Some nervous system disorders, including mental impairment, disturbed consciousness, memory loss and seizures, were also more common in patients randomised to strontium ranelate. Strontium ranelate provided gains in QALYs compared with no treatment in women with sufficient calcium and vitamin D intakes. The size of the QALY gain for each intervention was strongly related to the absolute risk of fracture. From the algorithm used, it is seen that strontium ranelate can be used cost-effectively in women at relatively high risk of osteoporotic fracture. However, the results of the probabilistic sensitivity analysis, using efficacy data from randomised controlled trials, suggest that it is not as cost-effective as alendronate, a comparator intervention from the bisphosphonate class. The use of strontium ranelate in women without a prior fracture will be dependent on identification algorithms being produced in conjunction with the National Institute for Health and Clinical Excellence Osteoporosis Guidelines Development Group. CONCLUSIONS: Strontium ranelate was shown to be clinically effective in the prevention of osteoporotic fractures. Scenarios have been found where strontium ranelate can be used cost-effectively, however given the probabilistic sensitivity analyses conducted, this intervention appears to be less cost-effective than the bisphosphonate alendronate. The evidence base for the efficacy of fracture prevention for strontium ranelate needs to be strengthened, particularly for hip fractures, where there is currently a non-significant reduction. If it were believed that the efficacy of strontium ranelate is dependent on either age or absolute risk, this would need to be proven. The evidence base on the T-score by age of the general female population needs to be strengthened, particularly in women over the age of 80 years. The prevalence of risk factors associated with fracture rates, over and above that provided by bone mineral density, also needs to be significantly strengthened to ensure that the estimated number of women that could be cost-effectively treated is accurate. PMID- 17280623 TI - A systematic review of quantitative and qualitative research on the role and effectiveness of written information available to patients about individual medicines. AB - OBJECTIVES: To establish the role and value of written information available to patients about individual medicines from the perspective of patients, carers and professionals. To determine how effective this information is in improving patients' knowledge and understanding of treatment and health outcomes. DATA SOURCES: Electronic databases searched to late 2004, experts in information design, and stakeholder workshops (including patients and patient organisations). REVIEW METHODS: Data from selected studies were tabulated and the results were qualitatively synthesised along with findings from the information design and stakeholder workshop strands. RESULTS: Most people do not value the written information they receive. They had concerns about the use of complex language and poor visual presentation and in most cases the research showed that the information did not increase knowledge. The research showed that patients valued written information that was tailored to their individual circumstances and illness, and that contained a balance of harm and benefit information. Most patients wanted to know about any adverse effects that could arise. Patients require information to help decision-making about whether to take a medicine or not and (once taking a medicine) with ongoing decisions about the management of the medicine and interpreting symptoms. Patients did not want written information to be a substitute for spoken information from their prescriber. While not everyone wanted written information, those who did wanted sufficient detail to meet their need. Some health professionals thought that written information for patients should be brief and simple, with concerns about providing side-effect information. They saw increasing compliance as a prime function, in contrast to patients who saw an informed decision not to take a medicine as an acceptable outcome. CONCLUSIONS: The combination of a quantitative and qualitative review, an exploration of best practice in information design, plus the input of patients at stakeholder workshops, allowed this review to look at all perspectives. There is a gap between currently provided leaflets and information which patients would value and find more useful. The challenge is to develop methods of provision flexible enough to allow uptake of varying amounts and types of information, depending on needs at different times in an illness. This review has identified a number of areas where future research could be improved in terms of the robustness of its design and conduct, and the use of patient-focused outcomes. The scope for this research includes determining the content, delivery and layout of statutory leaflets that best meet patients' needs, and providing individualised information, which includes both benefit and harm information. In particular, studies of the effectiveness and role and value of Internet-based medicines information are needed. PMID- 17280626 TI - [Intubation of patients with central nervous system trauma--should we or shouldn't we?]. PMID- 17280624 TI - Oral naltrexone as a treatment for relapse prevention in formerly opioid dependent drug users: a systematic review and economic evaluation. AB - OBJECTIVES: To investigate the clinical effectiveness and cost-effectiveness of naltrexone for relapse prevention in detoxified formerly opioid-dependent individuals compared with any strategy that does not use naltrexone, including treatment with placebo, other pharmacological treatments, psychosocial interventions or no treatment. DATA SOURCES: Major electronic databases were searched from inception to September 2005. REVIEW METHODS: Selected studies were screened and quality assessed. Meta-analyses were carried out as appropriate. A decision-analytic model using Monte Carlo simulation was developed that compared naltrexone as an adjunctive therapy to no naltrexone. It assumed compliance rates that were not enhanced by contingent management rewards (because this is current UK practice). Utility values could not be identified from the literature and so were obtained by research specially commissioned from the Value of Health Panel. RESULTS: The methodological quality of the 26 randomised controlled trials (RCTs) that met the inclusion criteria was poor to moderate. The results suggest that naltrexone as maintenance therapy may be better than placebo in terms of retention in treatment, but this was not statistically significant. A meta analysis of seven included RCTs gave the relative risk (RR) of loss of retention in treatment in the naltrexone arm as 0.94. The pooled hazard ratio (HR) reported in five of the RCTs for retention in treatment data followed up to 35 weeks was calculated as 0.90 in favour of naltrexone and also did not reach statistical significance. The risk of drug abuse in naltrexone versus placebo, with or without psychological support given in both arms, gave a pooled RR of 0.72, which was a statistically significant difference in favour of naltrexone. The pooled HR from three RCTs for opioid relapse-free rates was significantly different from placebo in favour of naltrexone 0.53; however, this fell off over time and may be of limited clinical significance. The RR of reimprisonment while on naltrexone therapy showed results in favour of naltrexone in the combined two studies of parolees or people on probation, but the number of participants was small. One study of 52 participants found that the difference in improvement score for risky sexual behaviour in the naltrexone group compared with the placebo group was not statistically significant. The adverse events data reported showed no significant difference between the naltrexone and placebo arms. The quality of the nine RCTs of interventions designed to increase retention with naltrexone was poor to moderate; however, all three different modalities of enhanced care showed some evidence of effectiveness. All of the contingency management programmes used incentive vouchers; the mean duration of treatment retention was 7.4 weeks for the contingency management intervention compared with 2.3-5.6 weeks for the naltrexone treatment alone. The mean length of time for which patients stayed on naltrexone was 84-103 days with additional psychosocial therapy compared with 43 64 days for the control group. In trials with added pharmacological agents the RRs of stopping treatment were 1.63 at 6 months and 1.31 at 12 months (in favour of naltrexone plus fluoxetine). It became statistically significant at 6 months, but not at 12 months. A meta-analysis of the RR of stopping treatment at week 12 (the minimum follow-up period) was carried out using six of the nine studies. The pooled RR of stopping treatment was 0.81. The results indicated that overall the intervention groups had 19% fewer patients who stopped treatment compared with the control group, but there was only a small number of studies and their quality was relatively poor. No existing economic evaluations were identified. The point estimate for the cost-effectiveness of naltrexone was pound42,500 per quality adjusted life-year (QALY). Sensitivity analysis was carried out and the incremental cost-effectiveness ratio varied between pound34,600 and pound42,500 per QALY gained. CONCLUSIONS: Following successful withdrawal from opioids, naltrexone may be administered on a chronic basis to block any future effects of opioids. Naltrexone appears to have some limited benefit in helping formerly opioid-dependent individuals to remain abstinent, although the quality of the evidence is relatively poor and heterogeneous. The limited quality and extent of the studies precluded an analysis of subgroups likely to benefit from naltrexone prescribing. Oral naltrexone is used infrequently in current UK practice, and this review suggests that this is appropriate as there is little evidence to support its wider implementation. There is an important deficit in information about the quality of life of people who use illicit opioids and this would perhaps be a worthwhile area of research in informing policy questions about the cost-effectiveness of different programmes and interventions. PMID- 17280627 TI - [Idiopathic osteoarthritis of the hip]. PMID- 17280628 TI - [Femoro-acetabular impingement: a cause of groin pain and early hip osteoarthritis in younger patients]. AB - In Denmark, approximately 7,000 hip joints are replaced by total hip arthroplasties annually. In 80% of the cases, the diagnosis is idiopathic end stage osteoarthritis. Scientifically this is hardly acceptable. However, the last decade has witnessed a proliferative research in biomechanically important, often subtle, malformations of the hip joint which are thought to play an important role pathogenetically for the development of hip osteoarthritis and hip pain especially in younger, active patients. The common denominator for these malformations is that they cause femoro-acetabular impingement during hip flexion and internal rotation. Repetitive microtrauma damages the acetabular labrum and cartilage, and the osteoarthritic cascade is initiated in earnest. This review evaluates new research relating to this paradigm. PMID- 17280629 TI - [Hip dysplasia: clinical assessment, radiologic evaluation and reference]. AB - Hip dysplasia is a common congenital disorder, and identified as a source of pain, functional impairment and increased risk for development of osteoarthritis. Early diagnosis and reference is essential in symptomatic hip dysplasia, since patients may be candidates for joint preserving surgery. Assessment concentrates on history, physical examination and plain radiography. If radiography confirms the diagnosis (CE-angle < 25 degrees), the patient should be referred for expert evaluation. The assessment of hip dysplasia should be well-known to GPs, orthopaedics and radiologists. PMID- 17280630 TI - [Glasgow Coma Scale < 9 as a criterion for tracheal intubation of patients with traumatic brain injuries?]. AB - Guidelines use GCS < 9 as a criterion for tracheal intubation of patients with traumatic brain injuries. Our hypothesis was that there was actually no evidence for using this criterion. We searched relevant databases and found no association between a particular GCS and impaired pharyngeal control, but we did find an association between a low GCS and respiratory insufficiency. Our findings suggest that patients with traumatic brain damages should be monitored closely using GCS as a supplement in the overall assessment of respiratory insufficiency. PMID- 17280631 TI - [Conduction anesthesia]. PMID- 17280632 TI - [Molecular diagnosis of CHARGE syndrom]. AB - CHARGE (coloboma, heart defects, atresia choanae, retarded growth and development, genital anomalies, ear anomalies) is a genetically heterogeneous syndrome in which CHD7 (chromodomain helicase DNA-binding protein 7) mutations account for about 60% of the cases. There is no obvious genotype-phenotype correlation but the majority of the patients fulfils the diagnostic criteria previously proposed. CHARGE syndrome should be considered in children with facial asymmetry, colobomas or choanal atresia; ear abnormalities are of great diagnostic value. PMID- 17280633 TI - [The effect of glucosamine sulphate on the blood levels of cholesterol or triglycerides--a clinical study]. AB - INTRODUCTION: This study was conducted in order to determine if glucosamine sulphate taken by patients as treatment for chronic joint pain influences the fasting blood levels of cholesterol and triglycerides. MATERIALS AND METHODS: A 3 months', post-marketing, randomised, double-blinded, placebo-controlled, clinical trial was performed with parallel groups of 66 patients over 40 years of age with joint pain of long duration receiving either recommend dosage (1500 mg per day) of glucosamine sulphate or placebo. The primary outcome measures were cholesterol levels (total cholesterol, LDL (low density lipoprotein)-cholesterol and HDL (high density lipoprotein)-cholesterol) and triglycerides in fasting blood (plasma levels). Secondary outcome measures were self reported side-effects. RESULTS: No significant differences between the glucosamine sulphate group and the placebo group with respect to cholesterol and triglycerides were observed. There were no differences between the treatment groups with respect to side effects. CONCLUSION: This study demonstrates that glucosamine sulphate does not significantly influence blood levels of cholesterol or triglycerides. PMID- 17280634 TI - [Focal nodular hyperplasia]. AB - INTRODUCTION: Focal nodular hyperplasia (FNH) is a benign lesion of the liver and is most commonly seen in women in the reproductive age. This article is a retrospective study of FNH. MATERIAL AND METHOD: Patients with histologically verified FNH were included. The relationship between tumor size, sex and estrogen was investigated. RESULTS: 24 patients were included. In 19 cases, the diagnosis was made coincidentally during the investigation or treatment of another disease. There was no difference in average tumor-size between sexes, but estrogen-treated women had larger tumors. Biopsies were needed in order to establish the diagnosis and to rule out malignancy. In most cases, the chosen strategy of management was expectancy rather than surgery. CONCLUSION: FNH is a benign liver disease and is often diagnosed coincidentally. An association between tumor size and estrogen treatment remains elusive. Diagnostic Imaging with contrast enhancement may produce characteristic features of FNH. However, biopsy remains the best option to diagnose FNH and to rule out malignancy. PMID- 17280635 TI - [Prenatal screening and diagnostics after infertility treatment]. AB - Women who get pregnant after infertility treatment differ from women with naturally conceived pregnancies concerning prenatal screening: on average they are older and therefore they have a greater risk of carrying a child with Down's syndrome, their children have an increased risk of congenital malformations, and they have a great wish to avoid invasive prenatal diagnostic tests. The conclusion of this review is that first trimester screening is an acceptable choice for these women, although larger studies are needed to clarify whether a correction factor is necessary for the biochemical markers. PMID- 17280636 TI - [Treatment of rheumatoid arthritis (RA) with anti-TNF-alpha antibody (Remicade). Individual monitoring of bioavailability and immunogenicity--secondary publication]. AB - Remicade/infliximab is effective in rheumatoid arthritis (RA), but response failure is frequent. Sera from 106 RA patients were monitored using an RIA for functional infliximab and an RIA for anti-infliximab antibody (Ab). S-infliximab varied considerably, e.g. 0-22 microg/ml before the 3rd infusion, and 44% were Ab positive after 6 months. Low s-infliximab was associated with Ab development and later therapeutic failure, and high Ab levels could be related to dose increases, side-effects and cessation of therapy. Pharmacological monitoring should help optimize anti-TNF therapies. PMID- 17280637 TI - [Severe anterior myocardial infarction caused by amphetamine abuse]. AB - We present a case showing that intake of amphetamine can cause severe anterior myocardial infarction with acute severe pump failure. Acute angiography revealed massive proximal thrombotic occlusion of the LAD, the first diagonal branch and septal branches in a 28-year-old man. Thrombectomy, balloon dilation and stenting were performed. Spasm thrombus interplay was found to be the likely mechanism. Due to the massive infarction, extremely depressed left ventricular performance and hemodynamic instability, the patient underwent successful heart transplantation. The patient was readmitted to hospital six months later due to chronic vascular rejection of the heart, which lead to the death of the young man. PMID- 17280638 TI - [Acute coronary syndrome after a single dose of amphetamine]. AB - Only 10% of patients with myocardial infarction (MI) have normal coronary arteriograms. It is well known that cocaine and amphetamines may induce myocardial infarction and stroke. A 24-year-old male was admitted after intake of a so-called amphetamine bomb. He had no chest pain. NSTEMI was confirmed by ECG and troponin-T outflow. The coronary arteriogram on day 6 was normal. It is suggested that all patients, even young persons, who are admitted for amphetamine intoxication should be evaluated for acute coronary syndrome, independent of chest pain status. PMID- 17280639 TI - Evidence from a response choice task reveals a selection bias in the attentional cueing paradigm. AB - In a typical attentional cueing paradigm, irrelevant peripheral cues produce early facilitation (fast responses) followed by later inhibition (slow responses) to cued locations. Here we examine whether cues not only influence the speed with which responses are produced, but also impact or bias which location is ultimately selected as requiring a response. Specifically, can cues influence not only the speed with which we respond but also influence the behavior produced? To examine this question, a choice localization task was used in which no targets were presented, and subjects were asked to choose which effector (left hand, right hand) to use in response to a centrally presented tone. Thus, following either a left or right peripheral cue, and then a central tone, subjects were free to respond with either their left or right hand. Early facilitation and later inhibition with this choice procedure were found in both response times and the proportion of responses to the cued and uncued locations. These results suggest that there are processes which initially bias response selection toward cued locations and then subsequently bias response selection away from cued locations. PMID- 17280641 TI - Inactivation of E. coli pyruvate formate-lyase: role of AdhE and small molecules. AB - Escherichia coli AdhE has been reported to harbor three distinct enzymatic activities: alcohol dehydrogenase, acetaldehyde-CoA dehydrogenase, and pyruvate formate-lyase (PFL) deactivase. Herein we report on the cloning, expression, and purification of E. coli AdhE, and the re-investigation of its purported enzymatic activities. While both the alcohol dehydrogenase and acetaldehyde-CoA dehydrogenase activities were readily detectable, we were unable to obtain any evidence for catalytic deactivation of PFL by AdhE, regardless of whether the reported cofactors for deactivation (Fe(II), NAD, and CoA) were present. Our results demonstrate that AdhE is not a PFL deactivating enzyme. We have also examined the potential for deactivation of active PFL by small-molecule thiols. Both beta-mercaptoethanol and dithiothreitol deactivate PFL efficiently, with the former providing quite rapid deactivation. PFL deactivated by these thiols can be reactivated, suggesting that this deactivation is non-destructive transfer of an H atom equivalent to quench the glycyl radical. PMID- 17280642 TI - Redox control of fast ligand dissociation from Escherichia coli cytochrome bd. AB - Bacterial bd-type quinol oxidases, such as cytochrome bd from Escherichia coli, contain three hemes, but no copper. In contrast to heme-copper oxidases and similarly to globins, single electron-reduced cytochrome bd forms stable complexes with O(2), NO and CO at ferrous heme d. Kinetics of ligand dissociation from heme d(2+) in the single electron- and fully-reduced cytochrome bd from E. coli has been investigated by rapid mixing spectrophotometry at 20 degrees C. Data show that (i) O(2) dissociates at 78 s(-1), (ii) NO and CO dissociation is fast as compared to heme-copper oxidases and (iii) dissociation in the single electron-reduced state is hindered as compared to the fully-reduced enzyme. Presumably, rapid ligand dissociation requires reduced heme b(595). As NO, an inhibitor of respiratory oxidases, is involved in the immune response against microbial infection, the rapid dissociation of NO from cytochrome bd may have important bearings on the patho-physiology of enterobacteria. PMID- 17280643 TI - Stem cell regulatory function mediated by expression of a novel mouse Oct4 pseudogene. AB - Multiple pseudogenes have been proposed for embryonic stem (ES) cell-specific genes, and their abundance suggests that some of these potential pseudogenes may be functional. ES cell-specific expression of Oct4 regulates stem cell pluripotency and self-renewing state. Although Oct4 expression has been reported in adult tissues during gene reprogramming, the detected Oct4 signal might be contributed by Oct4 pseudogenes. Among the multiple Oct4 transcripts characterized here is a approximately 1 kb clone derived from P19 embryonal carcinoma stem cells, which shares a approximately 87% sequence homology with the parent Oct4 gene, and has the potential of encoding an 80-amino acid product (designated as Oct4P1). Adenoviral expression of Oct4P1 in mesenchymal stem cells promotes their proliferation and inhibits their osteochondral differentiation. These dual effects of Oct4P1 are reminiscent of the stem cell regulatory function of the parent Oct4, and suggest that Oct4P1 may be a functional pseudogene or a novel Oct4-related gene with a unique function in stem cells. PMID- 17280640 TI - Changes in select redox proteins of the retinal pigment epithelium in age-related macular degeneration. AB - PURPOSE: To examine changes of select reduction-oxidation (redox) sensitive proteins from human donor retinal pigment epithelium (RPE) at four stages of age related macular degeneration (AMD). DESIGN: Experimental study. METHODS: Human donor eyes were obtained from the Minnesota Lions Eye Bank and graded using the Minnesota Grading System (MGS) into four stages that correspond to stages defined by the age-related eye disease study (AREDS). Protein content in RPE homogenates was measured using Western immunoblotting with protein-specific antibodies. RESULTS: The content of several antioxidant enzymes and specific proteins that facilitate refolding or degradation of oxidatively damaged proteins increased significantly in MGS stage 3. These proteins are involved in the primary (copper zinc superoxide dismutase [CuZnSOD], manganese superoxide dismutase [MnSOD], and catalase) and secondary (heat shock protein [HSP] 27, HSP 90, and proteasome) defense against oxidative damage. Additionally, the insulin pro-survival receptor exhibited disease-related upregulation. CONCLUSIONS: The pattern of protein changes identified in human donor tissue graded using the MGS support the role of oxidative mechanisms in the pathogenesis and progression of AMD. The MGS uses nearly identical clinical definitions and grading criteria of AMD that are used in the AREDS, so our results apply to clinical and epidemiologic studies using similar definitions. Results from our protein analysis of human donor tissue helps to explain altered oxidative stress regulation and cell-survival pathways that occur in progressive stages of AMD. PMID- 17280644 TI - Self-paced working memory: validation of verbal variations of the n-back paradigm. AB - Self-paced versions of many paradigms could have utility in probing cognitive systems. To validate several self-paced n-back paradigms, fourteen subjects performed four variations of the working memory task using visually presented letters as stimuli. Several areas in the frontal lobe, the anterior cingulate and a parietal network were consistently activated in the four variations: identity of black letters, location of black letters, color of colored letters and identity of colored letters. Since the n-back task is one of the more popular methods of investigating working memory, we validated the utility of several self paced versions in normal subjects via quantitative, coordinate-based meta analyses. The self-paced results agree well with meta-analyses and other published results, giving confidence that a self-paced n-back paradigm is robust in multiple variations. Behavioral results differ from other published reports, perhaps offering insight into true working memory strategy in normal subjects. PMID- 17280645 TI - Genetic association between polymorphisms of Pen2 gene and late onset Alzheimer's disease in the North Chinese population. AB - Presenilin enhancer 2 (Pen2) is a subunit of the gamma-secretase complex which cleaves amyloid precursor protein (APP) to generate amyloid beta (Abeta). We performed a systematic screening of all Pen2 exons and introns using direct sequencing to assess its role in the risk of developing late onset Alzheimer's disease (LOAD). 947 subjects (LOAD: 467; CONTROLS: 480) were recruited for this study. We obtained three polymorphisms: rs10402601, rs3817622, and rs2293688. Among these three polymorphisms, there was an interaction between rs3817622 and apolipoprotein E (APOE) genotypes (P=0.002). In the subjects with APOE 4 allele, there was a significant difference in the distribution of alleles (P=0.003) and genotypes (P=0.007) between LOAD and control groups. ORs [95% confidence interval (CI)] of allele A and T/A+A/A genotypes were respectively 4.720 (1.517-10.654) and 3.886 (1.381-10.932) with allele T and genotype T/T as a reference. Our results suggest that there is an association between rs3817622 and the development of LOAD in APOE epsilon4 carriers within the northern Chinese population. It is possible allele A of the Pen2 gene increases the risk for LOAD. PMID- 17280646 TI - Rifampicin protects PC12 cells against MPP+-induced apoptosis and inhibits the expression of an alpha-Synuclein multimer. AB - The potential cytoprotective effects of the anti-leprosy antibiotic rifampicin were investigated in rat pheochromocytoma (PC12) cells prior to intoxication with 1-Methyl-4-phenyl pyridinium (MPP(+)). MPP(+) induced both apoptotic and necrotic cell death, and increased the expression of a 57 kDa species of alpha-Synuclein. This species of alpha-Synuclein is larger than the monomer, and is therefore an oligomer or an aggregated form of the protein. Rifampicin significantly increased survival of these catecholaminergic cells in a concentration-dependent manner. The expression of the higher molecular mass alpha-Synuclein was increased by MPP(+) exposure, and its expression was inversely related to cell survival in the rifampicin-treated cells. Importantly, rifampicin suppressed apoptosis almost completely, without shifting the death cascade to necrosis, which is a problem that has been reported with caspase inhibitors of apoptosis (Hartmann, A., Troadec, J.D., Hunot, S., Kikly, K., Faucheux, B.A., Mouatt-Prigent, A., Ruberg, M. Agid, Y., Hirsch, E.C., 2001. Caspase-8 is an effector in apoptotic death of dopaminergic neurons in Parkinson's disease, but pathway inhibition results in neuronal necrosis. J. Neurosci. 21, 2247-2255). These results suggest that rifampicin improves survival of catecholamine- and alpha-Synuclein-containing cells, which degenerate in Parkinson's disease (PD), and thus may be therapeutic in this disease. PMID- 17280647 TI - Widespread expression of ErbB2, ErbB3 and ErbB4 in non-human primate brain. AB - Neuregulin (NRG) signaling proteins interact with ErbB receptors leading to the proliferation, differentiation and migration of neurons and glia in the developing brain. NRG-1/ErbB4 are susceptibility genes for schizophrenia, yet little is known about the neuroanatomical expression of ErbB receptors specifically in primates. We find widespread expression of ErbB2, ErbB3 and ErbB4 receptor mRNAs throughout the telencephalon of juvenile and adult monkeys with in situ hybridization, with ErbB2 and ErbB4 mRNA more abundant than ErbB3 mRNA. ErbB2 and ErbB4 mRNA are expressed at higher levels in grey matter compared to white matter, whereas ErbB3 mRNA is expressed at low levels in both grey and white matter. We also characterized ErbB protein expression with immunoblotting and immunohistochemistry. In frontal cortex, ErbB2, ErbB3 and ErbB4 antibodies immunostained neuronal soma and nuclei. The ErbB2 antibody also immunostained glia at the pial surface. Within white matter, ErbB3 and ErbB4 proteins were localized to putative interstitial white matter neurons while ErbB2 protein was found in glia. Western blotting revealed immunopositive bands at approximately 180-200 kDa for each ErbB, which is consistent with the size of full-length ErbBs. Smaller immunopositive bands were also identified for each ErbB receptor in whole brain homogenates and separate cytoplasmic and nuclear extracts suggesting nuclear ErbB-back-signaling capacity in the brain. The ubiquitous expression of ErbB receptors indicates that many cell populations throughout the brain of juvenile and adult primates have the potential to respond to NRG-1 in a variety of ways. PMID- 17280648 TI - Family-based association study of 5-HTTLPR and the 5-HT2A receptor gene polymorphisms with autism spectrum disorder in Korean trios. AB - The potential role of the serotoninergic system in the development of autistic disorder has long been suggested based on the observation of hyperserotoninemia in autistic subjects and the results of drug treatment studies. Promoter region polymorphisms (5-HTTLPR) of the serotonin transporter gene (SLC6A4) and the 5 HT2A receptor gene (HTR2A) have been studied as potential candidate genes in autism spectrum disorder (ASD). The objective of this family-based linkage/association study is to evaluate the relationship between ASD and 5 HTTLPR as well as that between some SNPs of HTR2A and ASD in Korean trios by using the transmission disequilibrium test (TDT). Genotyping was performed for 5 HTTLPR and two single nucleotide polymorphisms (SNPs) (-1438G/A and 102T/C) of HTR2A. The TDT, linkage disequilibrium (LD) analysis and haplotype analysis were performed. This study comprised 126 complete trios of ASD patients and both parents. With regard to the transmission of 5-HTTLPR, the long allelic variant was preferentially transmitted in the ASD subjects. Based on the TDT results, there was no significant difference in the transmission of the two SNPs of HTR2A. However, in the results of the haplotype analysis, the AT haplotype demonstrated significant evidence of association with autism. The global chi(2) test for haplotype transmission revealed a significant association between HTR2A and autism. Although we identified a significant association between ASD and 5-HTTLPR as well as between ASD and HTR2A, it cannot exclude the chance finding because of the low level of statistical significance and relatively small power. We believe that further studies are required to examine the relationship between serotonin related genes and the behavioral phenotypes of ASD in the Korean population. PMID- 17280649 TI - Characterization of thoracic spinal neurons with noxious convergent inputs from heart and lower airways in rats. AB - Respiratory symptoms experienced in some patients with cardiac diseases may be due to convergence of noxious cardiac and pulmonary inputs onto neurons of the central nervous system. For example, convergence of cardiac and respiratory inputs onto single solitary tract neurons may be in part responsible for integration of regulatory and defensive reflex control. However, it is unknown whether inputs from the lungs and heart converge onto single neurons of the spinal cord. The present aim was to characterize upper thoracic spinal neurons responding to both noxious stimuli of the heart and lungs in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. A catheter was placed in the pericardial sac to administer bradykinin (BK, 10 microg/ml, 0.2 ml, 1 min) as a noxious cardiac stimulus. The lung irritant, ammonia, obtained as vapor over a 30% solution of NH(4)OH was injected into the inspiratory line of the ventilator (0.5-1.0 ml over 20 s). Intrapericardial bradykinin (IB) altered activity of 58/65 (89%) spinal neurons that responded to inhaled ammonia (IA). Among those cardiopulmonary convergent neurons, 81% (47/58) were excited by both IA and IB, and the remainder had complex response patterns. Bilateral cervical vagotomy revealed that vagal afferents modulated but did not eliminate responses of individual spinal neurons to IB and IA. The convergence of pulmonary and cardiac nociceptive signaling in the spinal cord may be relevant to situations where a disease process in one organ influences the behavior of the other. PMID- 17280650 TI - Optic nerve transection affects development and use-dependent plasticity in neocortex of the rat: Quantitative acetylcholinesterase imaging. AB - We investigated the effects of neonatal optic nerve transection on cortical acetylcholinesterase (AChE) activity in hooded rats during postnatal development and following behavioral manipulation after weaning. AChE reaction product was quantified on digitized images of histochemically stained sections in layer IV of primary somatic sensory, primary visual and visual association cortex. Rats with optic nerve transection were compared to sham-operated littermates. In all cortical regions of both types of animal, AChE reaction product was increased to peak 2 weeks after birth and decreased thereafter, reaching adult levels at the end of the third postnatal week. During postnatal development, reaction product in primary visual cortex was lower in rats deprived of retinal input than in sham operated littermates and the area delineated by reaction product was smaller. However, optic nerve transection did not modify the time course of postnatal development or statistically significantly diminish adult levels of AChE activity. Behavioral manipulations after weaning statistically significantly increased enzyme activity in sham-operated rats in all cortical areas examined. Compared with cage rearing, training in a discrimination task with food reward had a greater impact than environmental enrichment. By contrast, in the rats with optic nerve transection enrichment and training resulted in statistically significantly increased AChE activity only in lateral visual association cortex. Our findings provide evidence for intra- and supramodal influences of the neonatal removal of retinal input on neural activity- and use-dependent modifications of cortical AChE activity. The laminar distribution of the AChE reaction product suggests that the observed changes in AChE activity were mainly related to cholinergic basal forebrain afferents. These afferents may facilitate the stabilization of transient connections between the somatic sensory and the visual pathway. PMID- 17280651 TI - Characterization of di- and monosulfated, unsaturated heparin disaccharides with terminal N-sulfated 1,6-anhydro-beta-D-glucosamine or N-sulfated 1,6-anhydro-beta D-mannosamine residues. AB - Modified heparin disaccharides were obtained by the alkaline treatment of a solution containing the disulfated heparin disaccharide DeltaHexA-alpha-(1-->4)-D GlcNSO(3),6SO(3). Their structures were characterized by one- and two-dimensional NMR spectroscopy: DeltaHexA-alpha-(1-->4)-1,6-anhydro-GlcNSO(3), DeltaHexA-alpha (1-->4)-1,6-anhydro-ManNSO(3) and DeltaHexA-alpha-(1-->4)-ManNSO(3),6OSO(3). NMR spectroscopy, in combination with HPLC, provided the composition of the mixture. Characteristic NMR signals of the disaccharides were identified, even at low levels, in a high field of (1)H-(13)C correlation NMR spectra (HSQC) of a low molecular weight heparin (LMWH) obtained by beta-elimination (alkaline hydrolysis) of heparin benzyl ester, providing a more complete structural profile of this class of compounds. PMID- 17280652 TI - Electrospray ionization mass spectrometry of oligosaccharides derived from fucoidan of Ascophyllum nodosum. AB - Algal fucoidan is a complex sulfated polysaccharide whose structural characterization requires powerful spectroscopic methodologies. While most of the structural investigations reported so far have been performed using NMR as the main spectroscopic method, we report herein data obtained by negative electrospray ionization mass spectrometry. MS analysis has been carried out on oligosaccharides obtained by partial hydrolysis of fucoidan from the brown algae Ascophyllum nodosum. Oligosaccharide mixtures were fractionated by size exclusion chromatography, which allowed the analysis of oligomers ranging from monosaccharide to pentasaccharide. Monosaccharides were detected as monosulfated as well as disulfated forms. Besides, part of the oligosaccharides exhibited a high content of sulfate, evidencing that fucoidan contains disulfated fucosyl units. Fragmentation experiments yielded characteristic fragment ions indicating that the fucose units are mainly 2-O-sulfated. This study demonstrates that highly sulfated oligosaccharides from fucoidan can be analyzed by ESIMS which gives additional information about the structure of this highly complex polysaccharide. PMID- 17280653 TI - Direct dissolution of cellulose in NaOH/thiourea/urea aqueous solution. AB - Untreated cellulose was directly and quickly dissolved in NaOH/thiourea/urea aqueous solution. The mechanism of dissolution was investigated by SEM, WXRD and (13)C NMR. The components of this solvent cannot dissolve cellulose on their own, and the interactions between NaOH and urea, as well as between NaOH and thiourea, play an important role in improving the dissolution of cellulose. Moreover, (13)C NMR spectra proved that NaOH, thiourea, and urea were bound to cellulose molecules, which brings cellulose molecules into aqueous solution to a certain extent and prevents cellulose macromolecules from associating. (13)C NMR spectra of the cellulose solution show that this novel mixture is a direct solvent. Optical microscopy and CP MAS (13)C NMR were used to study the process of dissolution. The results reveal that cellulose is dissolved completely and that cellulose I (cotton linter) first changes to amorphous cellulose chains in solution, and then to cellulose II during regeneration. Moreover, a new, more effective dissolution method is proposed, as confirmed by dynamic rheology measurements. PMID- 17280654 TI - Readers' choice: hot papers downloaded in 2006. PMID- 17280655 TI - Hypoxia and its downstream targets in DMBA induced mammary carcinoma: protective role of Semecarpus anacardium nut extract. AB - Tumors are usually exposed to a hypoxic microenvironment due to their irregular growth and abnormal vascular supply. Under hypoxia, gene regulation (selective activation and inactivation of genes) plays an important role in maintenance of tumor. Multiple hypoxic and angiogenic growth factors are expressed for tumor cell survival. In search of novel anticancer drug, Semecarpus anacardium nut extract (SA) was tried against breast cancer. Mammary carcinoma was induced in vivo by 7,12-dimethyl benz(a) anthracene (DMBA) (25mg/kg b.w., p.o.). Tumor development and vascular structures were accelerated by DMBA. Hypoxia inducible factor-1 alpha (HIF-1) was coexpressed with its downstream genes in mammary tissue. Cancer rats were then treated with S. anacardium nut extract (SA) (250mg/kg b.w., p.o.). Delay in the tumor growth was paralleled with a drastic reduction in vascularization by SA treatment. Activities of glycolytic enzymes were normalized with decreased expression of glucose transporter-1 and carbonic anhydrase IX by drug treatment. Inhibition of HIF-1, vascular endothelial growth factor and inducible nitric oxide synthase by SA may in part explain its antiangiogenic action. SA also inhibits endothelial cell proliferation by blocking the overexpressed survival cytokines. In conclusion, our study demonstrates that at least some part of the antitumor activity of SA is due to the suppression of hypoxic and angiogenic factors. The mechanism of this inhibition seems to be through an action of SA on expression of HIF-1 and its downstream targets. PMID- 17280656 TI - Proximate composition, fatty acids, cholesterol, minerals in frozen red porgy. AB - The proximate composition of frozen red porgy (Pagrus pagrus) was determined. The moisture, ash, protein and total lipids (45.5+/-1.4% PL of which 90.4+/-2.0% PhL) were found to be 71.7+/-1.0%, 1.73+/-0.12%, 21.5+/-0.8% and 0.81+/-0.09% of the wet muscle tissue, respectively. 16:0 and 18:0 were the main SFA, 18:1 (omega-9 and omega-7) the main MUFA while DHA, EPA and arachidonic acid were the main polyunsaturated fatty acids (PUFA). The SFA/PUFA ratio was 1.5 and the omega 3/omega-6 ratio was 3.02. The cholesterol content was found to be 8.18+/-0.34 mg/100 g of the wet muscle tissue. Ni, Cr, Mn, Cu, Zn, Fe and Mg were determined in the muscles, skin, hepatopancreas and head of the fish. The covering percentage of the recommended daily allowance/intake (RDA/RDI) for each mineral, in the muscle tissue, has been calculated to 14.2% (males) and 7.89% (females) for Fe, 2.87% for Cu, 4.07% for Zn 0.4% for Mn, 13.9% for Ni, 20.2% for Cr and 10.4% for Mg. PMID- 17280657 TI - Perceptual constraints and the learnability of simple grammars. AB - Cognitive processes are often attributed to statistical or symbolic general purpose mechanisms. Here we show that some spontaneous generalizations are driven by specialized, highly constrained symbolic operations. We explore how two types of artificial grammars are acquired, one based on repetitions and the other on characteristic relations between tones ("ordinal" grammars). Whereas participants readily acquire repetition-based grammars, displaying early electrophysiological responses to grammar violations, they perform poorly with ordinal grammars, displaying no such electrophysiological responses. This outcome is problematic for both general symbolic and statistical models, which predict that both types of grammars should be processed equally easily. This suggests that some simple grammars are acquired using perceptual primitives rather than general-purpose mechanisms; such primitives may be elements of a "toolbox" of specialized computational heuristics, which may ultimately allow constructing a psychological theory of symbol manipulation. PMID- 17280658 TI - Developing symbolic capacity one step at a time. AB - The present research examines the ability of children as young as 4 years to use models in tasks that require scaling of distance along a single dimension. In Experiment 1, we found that tasks involving models are similar in difficulty to those involving maps that we studied earlier (Huttenlocher, J., Newcombe, N., & Vasilyeva, M. (1999). Spatial scaling in young children. Psychological Science, 10, 393-398). In Experiment 2, we found that retrieval tasks, where children indicate the location of a hidden object in an actual space are substantially more difficult than placement tasks, where children put a visible object in a particular location in an actual space. We discuss possible implications of the differential difficulty of retrieval and placement tasks for the understanding of symbolic development. PMID- 17280660 TI - Expression of CYP2S1 in human hepatic stellate cells. AB - Activated stellate cells are myofibroblast-like cells associated with the generation of fibrotic scaring in chronically damaged liver. Gene chip analysis was performed on cultured fibrotic stellate cells. Of the 51 human CYP genes known, 13 CYP and 5 CYP reduction-related genes were detected with 4 CYPs (CYP1A1, CYP2E1, CY2S1 and CYP4F3) consistently present in stellate cells isolated from three individuals. Quantitative RT-PCR indicated that CYP2S1 was a major expressed CYP mRNA transcript. The presence of a CYP2A-related protein and testosterone metabolism in stellate cell cultures suggest that stellate cells express specific functional isoforms of CYP of which a major form is CYP2S1. PMID- 17280661 TI - Stimulation of the nitric oxide/cyclic guanosine monophosphate signaling pathway elicits human sperm chemotaxis in vitro. AB - OBJECTIVE: To investigate whether nitric oxide (NO) may attract human spermatozoa via activation of the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway. DESIGN: Prospective study. SETTING: Academic research institution. PATIENT(S): Seven normozoospermic patients belonging to couples presenting for infertility evaluation. INTERVENTION(S): Sperm samples were processed by the swim-up technique. MAIN OUTCOME MEASURE(S): Sperm chemotaxis detected by a choice device (specially designed three-well plexiglass chamber), intracellular level of cGMP (by radioimmunoassay), and sperm motility parameters (by computer-assisted sperm analysis). RESULT(S): After a 20-minute incubation, the NO donor S-nitrosoglutathione (GSNO) increased the synthesis of cGMP and exerted a significant chemoattraction on human spermatozoa. The GSNO induced migration of sperm was inhibited by PTIO (a NO scavenger), ODQ (an sGC inhibitor), and Rp-8-Br-cGMPS (an inhibitor of cGMP-dependent protein kinases). The cell-permeating cGMP analog 8-Br-cGMP acted as a potent chemoattractant per se: this effect was inhibited by Rp-8-Br-cGMPS. CONCLUSION(S): These data suggest that NO may exert a chemoattractant effect on human spermatozoa and that the signal transduction involves the activation of sGC, the synthesis of cGMP, and the activation of cGMP-dependent protein kinases. PMID- 17280662 TI - Comparison of preovulatory follicular concentrations of epidermal growth factor, insulin-like growth factor-I, and inhibins A and B in women undergoing assisted conception treatment with gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists. AB - Follicular fluid contents of 69 age-matched women undergoing ovarian stimulation with a GnRH agonist and a GnRH antagonist were collected during oocyte retrieval. The groups did not differ in baseline characteristics and in terms of assisted conception treatment outcome. Similarly, follicular fluid levels of epidermal growth factor, insulin-like growth factor, and inhibins A and B were found not to be different. Our results suggest that follicular development in regard to ovarian growth factor dynamics is not different in women undergoing ovarian stimulation with GnRH antagonists than in women using GnRH agonists. PMID- 17280659 TI - Transient inactivation of Notch signaling synchronizes differentiation of neural progenitor cells. AB - In the developing nervous system, the balance between proliferation and differentiation is critical to generate the appropriate numbers and types of neurons and glia. Notch signaling maintains the progenitor pool throughout this process. While many components of the Notch pathway have been identified, the downstream molecular events leading to neural differentiation are not well understood. We have taken advantage of a small molecule inhibitor, DAPT, to block Notch activity in retinal progenitor cells, and analyzed the resulting molecular and cellular changes over time. DAPT treatment causes a massive, coordinated differentiation of progenitors that produces cell types appropriate for their developmental stage. Transient exposure of retina to DAPT for specific time periods allowed us to define the period of Notch inactivation that is required for a permanent commitment to differentiate. Inactivation of Notch signaling revealed a cascade of proneural bHLH transcription factor gene expression that correlates with stages in progenitor cell differentiation. Microarray/QPCR analysis confirms the changes in Notch signaling components, and reveals new molecular targets for investigating neuronal differentiation. Thus, transient inactivation of Notch signaling synchronizes progenitor cell differentiation, and allows for a systematic analysis of key steps in this process. PMID- 17280663 TI - Chronic stress in free-living European starlings reduces corticosterone concentrations and reproductive success. AB - Chronic increases in stress hormones such as glucocorticoids are maladaptive, yet studies demonstrating a causal relationship among chronic stress, increases in glucocorticoid concentrations, and subsequent fitness costs in free-living animals are lacking. We experimentally induced chronic psychological stress in female European starlings (Sturnus vulgaris) by subjecting half of the females at our study site to a chronic stress protocol consisting of 4, 30 min stressors (loud radio, predator calls, a novel object, or predator decoys including a snake, rat, and owl) administered in random order daily for 8 days after clutch completion. Experimental females were captured at the end of the chronic stress protocol (9 days after the onset of the chronic stress protocol), and unstressed control females were captured at the same stage of the nesting cycle. Chronically stressed females had lower baseline corticosterone (CORT, the avian glucocorticoid) concentrations and lower reproductive success than unstressed females. Furthermore, surviving nestlings in experimentally stressed broods showed sensitization of the CORT response to acute stress, which is a physiological change that could persist to adulthood. Attenuation of baseline CORT concentrations in adult females is contrary to the general assumption that elevated CORT concentrations indicate stress, suggesting that more research is necessary before CORT concentrations can be used to accurately assess chronic stress in field studies. PMID- 17280664 TI - Thyroid hormone-induced demineralisation of the vertebral skeleton of the eel, Anguilla anguilla. AB - The role of thyroid hormones (TH) in bone remodelling is controversial. Indeed, in humans, while they are necessary for normal growth and development, their overproduction can induce important mineral bone loss and osteoporosis. Intense bone resorption is a natural phenomenon also observed in some teleosts, during reproductive migration and fasting. Our work aimed at investigating the effects of chronic treatments with TH (thyroxin, T4 or triiodothyronine, T3) on bone resorption in a migratory fish, the European eel (Anguilla anguilla), a representative species of an ancient group of teleosts (Elopomorphs). The incineration method showed that TH induced a significant mineral loss in eel vertebral skeleton. Histology and histophysical (qualitative and quantitative microradiographs) methods were then applied to vertebral sections to determine which types of resorption were induced by TH. Quantitative image analysis of microradiographs showed that TH significantly increased the porosity of the vertebrae, demonstrating the induction of a severe bone loss. Histology revealed the appearance of large osteoclastic lacunae, indicating a stimulation of osteoclastic resorption. Quantitative image analysis of ultrathin microradiographs showed a significant increase of the size of osteocytic lacunae, indicating a stimulation of periosteocytic osteolysis. Finally, quantitative microradiographs indicated a significant fall of mineralisation degree. TH treatments did not stimulate the production of the calcium-bonded lipo-phospho protein vitellogenin, indicating that TH-induced bone demineralisation was not mediated by any indirect effect on vitellogenesis. Our study demonstrates that TH may participate in the mobilisation of bone mineral stores in the eel, by inducing different types of vertebral bone resorption, such as osteoclastic resorption and periosteocytic osteolysis. These data suggest that the stimulatory action of TH on bone resorption may be an ancient regulatory mechanism in vertebrates. PMID- 17280665 TI - The risk of malignancy index in discrimination of adnexal masses. AB - OBJECTIVE: To assess the ability of the risk of malignancy index (RMI) based on a serum CA125 level, ultrasound findings and menopausal status, to discriminate benign from malignant adnexal masses. METHOD: Between September 2002 and November 2004, 296 women with adnexal masses were enrolled. The sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the CA125 serum level, ultrasound findings and menopausal status in prediction of ovarian cancer were calculated and compared individually or combined into the RMI. RESULTS: The RMI identified malignant cases more accurately than any individual criterion in diagnosing ovarian cancer. Using a cut-off level of 153 to indicate malignancy, the RMI showed a sensitivity of 76.4%, a specificity of 77.9%, a PPV of 65.9%, a NPV of 85.5% with 79.4% correct diagnosis rate. CONCLUSION: The RMI is an appropriate method in diagnosing adnexal masses with high risk of malignancy and forwarding to gynecological oncology centers for suitable surgical operations. PMID- 17280666 TI - Increased postpartum blood loss in pregnancies associated with placental malaria. AB - OBJECTIVE: To determine the relationship of placental malaria and parity with postpartum blood loss in a malarious area of Tanzania. METHODS: A total of 706 uncomplicated vaginal deliveries were studied at Muhimbili University Hospital, Dar es Salaam, Tanzania. Maternal age, parity, date of delivery, birth weight, presence of placental malaria, stillbirths, and delivery complications were noted. Collection and measurement of vaginal blood loss commenced immediately following birth using a plastic vinyl sheet placed underneath the mother. The bed was divided in the middle to allow the blood to drain into a bucket. Blood loss was measured for a period of 2 h following delivery. RESULTS: In singleton births the mean postpartum blood loss was 170 mL in nulliparas and 187 mL in multiparas (p=0.017). Blood loss was 400 mL or greater in 23 women (3.4%) and 500 mL or greater in 10 women (1.5%). Mean postpartum bleeding tended to increase with maternal age, parity, and birth weight. In logistic regression the odds ratio for a blood loss of 400 mL or greater was significantly increased for women with placental malaria (3.2; 95% confidence interval, 1.1-9.0; p=0.028), after adjusting for a birth weight greater than 4000 g. Placental malaria showed a marked seasonal pattern, which corresponded to the months of peak prevalence for a postpartum blood loss of 400 mL or greater (p=0.007). CONCLUSION: A postpartum blood loss of 400 mL or greater should be considered a possible complication of placental malaria. PMID- 17280667 TI - Prevention of recurrent bacterial urinary tract infections by intravesical instillation of hyaluronic acid. AB - OBJECTIVE: To evaluate the efficacy of vesical instillation of hyaluronic acid against recurrent urinary tract infections. METHODS: Twenty women with a history of recurrent urinary tract infections each received 9 intravesical instillations of hyaluronic acid over 6 months. Their status was assessed prospectively over 47.6 weeks and compared with a retrospective review of patient charts covering 36.2+/-6.2 weeks. RESULTS: The total numbers of urinary tract infections were 67 before and 10 after treatment (p<0.001). Thirteen patients (65%) were free of recurrences until the end of the study. One had a recurrence during treatment, and 6 (30%) during follow-up. The number of infections per year per patient was reduced from 4.99+/-0.92 to 0.56+/-0.82 (p<0.001). In women with recurrences, time to recurrence was 178.3+/-25.5 days, compared with 76.7+/-24.6 days before treatment (p<0.001). CONCLUSION: Intravesical instillation of hyaluronic acid is effective in preventing recurrent urinary tract infections. PMID- 17280668 TI - The cross-sectional area of umbilical cord components in normal pregnancy. AB - OBJECTIVE: To determine the normal cross-sectional areas of the umbilical vein, umbilical artery, and Wharton jelly in healthy pregnancies, and correlate the obtained values with fetal anthropometric parameters. METHODS: A cross-sectional study was performed with 312 women between the 24th and 39th weeks of a normal pregnancy. The cross-sectional areas of umbilical cord vessels were measured at the junction of the cord and fetal abdomen, and the values were subtracted from the total cord cross-sectional area to assess the cross-sectional area of the Wharton jelly. The anthropometric parameters analyzed were biparietal diameter, head circumference, femur length, and estimated fetal weight, and the Spearman correlation was used to assess the correlation between the cross-sectional areas of umbilical cord components and fetal anthropometric parameters. A polynomial regression analysis was performed to identify the curves that best adjusted to mean and standard deviation according to gestational age. RESULTS: A statistically significant correlation was observed between the cross-sectional areas of cord components and fetal anthropometric parameters (P<0.001) as well as gestational age (P<0.001). CONCLUSIONS: Reference measurements of the cross sectional areas of umbilical cord components are important tools in the assessment of fetal growth. PMID- 17280670 TI - Amniotomy in labor. PMID- 17280669 TI - Alternatives to mifepristone for early medical abortion. AB - OBJECTIVE: To review published reports of first-trimester medical abortion regimens that do not include mifepristone. METHODS: Reports listed in Pubmed and Medline on prospective and controlled trials of the efficacy of misoprostol, alone or associated with methotrexate, for first-trimester abortion were analyzed if they included more than 100 participants and were published since 1990. RESULTS: The efficacy of regimens using misoprostol alone ranged from 84% to 96%, and when misoprostol was used with methotrexate the efficacy ranged from 70% to 97%. Efficacy rates were influenced by follow-up interval. Treatment for infection, bleeding, and incomplete abortion were infrequent with both methods (0.3%-5%). CONCLUSION: Alone or in combination with methotrexate, misoprostol is an efficacious alternative to mifepristone for the medical termination of pregnancy. PMID- 17280671 TI - Getting to know a stranger--rural nurses' experiences of mentoring: a grounded theory. AB - BACKGROUND: Mentoring is often proposed as a solution to the problem of successfully recruiting and retaining nursing staff. The aim of this constructivist grounded theory study was to explore Australian rural nurses' experiences of mentoring. DESIGN: The research design used was reflexive in nature resulting in a substantive, constructivist grounded theory study. PARTICIPANTS: A national advertising campaign and snowball sampling were used to recruit nine participants from across Australia. Participants were rural nurses who had experience in mentoring others. METHODS: Standard grounded theory methods of theoretical sampling, concurrent data collection and analysis using open, axial and theoretical coding and a story line technique to develop the core category and category saturation were used. To cultivate the reflexivity required of a constructivist study, we also incorporated reflective memoing, situational analysis mapping techniques and frame analysis. Data was generated through eleven interviews, email dialogue and shared situational mapping. RESULTS: Cultivating and growing new or novice rural nurses using supportive relationships such as mentoring was found to be an existing, integral part of experienced rural nurses' practice, motivated by living and working in the same communities. Getting to know a stranger is the first part of the process of cultivating and growing another. New or novice rural nurses gain the attention of experienced rural nurses through showing potential or experiencing a critical incidence. CONCLUSIONS: The problem of retaining nurses is a global issue. Experienced nurses engaged in clinical practice have the potential to cultivate and grow new or novice nurses-many already do so. Recognising this role and providing opportunities for development will help grow a positive, supportive work environment that nurtures the experienced nurses of tomorrow. PMID- 17280672 TI - The long-term experience of living with peripheral arterial disease and the recovery following revascularisation: a qualitative study. AB - BACKGROUND: The long-term experience of living with peripheral arterial disease (PAD) and the durability of improvements after revascularisation are sparsely described in the literature. The primary goals of medical treatment and nursing care for PAD are to provide relief of symptoms, improve quality of life, and prevent the progression of arterial disease and cardiovascular complications. The majority of patients are elderly with a significantly increased risk of myocardial infarction, stroke, and cardiovascular death. Which can limit mobility and functional status even in the absence of ischaemic claudication, rest pain, or ulceration after a successful revascularisation. OBJECTIVES: To illuminate the long-term experience of living with PAD and the recovery following revascularisation. METHODS: Fourteen patients were interviewed 6 months and 212 years after revascularisation. The transcribed texts were analysed using manifest and latent content analysis. RESULTS: The long-term experience of living with PAD meant gradually becoming aware of having a chronic disease. This was interpreted through the following themes, representing the transition from being in an acute phase of PAD to the recovery after revascularisation and entering a chronic phase of PAD: (I) 'becoming better but not cured'; (II) 'recapturing control over life'; (III) 'reappraising meaning in life'. CONCLUSIONS: Becoming aware of having a chronic disease results in a need to adapt to and accept permanent restrictions in daily life. The findings showed that revascularisations offer several benefits. However, when PAD symptoms were relieved, other ailments became discernable, which reflects the complex course of PAD and atherosclerotic disease. Moreover, several critical points and events such as other concurrent diseases, unrealistic hopes for recovery, and the complex course of PAD and atherosclerotic disease complicated the transition process towards health and well-being. PMID- 17280673 TI - Doctors' traits perceived by Japanese nurses as communication barriers: a questionnaire survey. AB - BACKGROUND: Studies addressing nurses' traits to improve the quality of nurse physician communication exist, whereas only a few studies exploring physicians' traits as communication barriers are conducted. OBJECTIVES: The purpose of this research is to determine what types of physicians do nurses find difficult to communicate with. To this end, we conducted a pilot study, consisting of semi structured interviews, with nine nurses. A questionnaire survey was then conducted to test the generalizability of the interviewees' opinions about physician traits that impede effective nurse-physician communication. DESIGN: A within-respondent factorial design was employed. Each respondent answered questions about two physicians whom she or he has found most difficult or easiest to communicate with. The order of physician type (easy vs. difficult) was counterbalanced. SETTINGS: The main study, a questionnaire survey, was administered at four Japanese hospitals. PARTICIPANTS: Participants were 310 nurses. The questionnaires were mailed to the person in charge of each hospital. The questionnaires were handed to the nurses by the person in charge. Three out of the four hospitals reported that a majority of their nurses answered the questionnaires. METHODS: The questionnaire asked respondents to evaluate how well various statements (e.g., Is the doctor moody?) fit a particular physician whom she or he has found most difficult or easiest to communicate with. RESULTS: A series of repeated-measures ANOVAs revealed that every statement was judged as fitting the description of doctors they found difficult better than that of doctors they found easy to talk to. An exploratory cluster analysis was conducted and it revealed that difficult characteristics of physicians can be divided into three subtypes. CONCLUSION: The questionnaire survey confirmed that opinions provided by interviewees in the pilot study were widely shared by other Japanese nurses. The study revealed that communication barriers between nurses and physicians are caused by the physicians' reluctance to communicate with nurses and the doctors' emotional difficulties. PMID- 17280674 TI - Explaining young registered Finnish nurses' intention to leave the profession: a questionnaire survey. AB - BACKGROUND: Regardless of the current global nursing shortage, many nurses are planning to leave their profession. According to previous research, young nurses in particular are the most eager to leave-there is, however, no research available as to why this is. OBJECTIVES: The aim of this survey study was to discover what proportion of young nurses intends to leave the profession in Finland and what the reasons behind this are. DESIGN: Quantitative, survey study. SETTINGS: Six hospital districts in Finland. PARTICIPANTS: A total of 147 Registered Nurses, under the age of 30, working mainly in hospitals. METHOD: Data was collected as part of the NEXT (Nurses Early Exit)--Study. A structured postal questionnaire, BQ-12, was used to collect the data in autumn 2003. Quantitative data were analysed using chi(2), the Fisher exact-test and Mann-Whitney U-test, and qualitative data were analysed using quasi-statistics. RESULTS: During the course of the past year, 26% of young nurses have often thought of giving up nursing. This was associated with personal burnout, poor opportunities for development, lack of affective professional commitment, low job satisfaction, work-family conflicts and higher quantitative work demands. In open-ended question, nurses stated that the main reasons for them considering leaving the profession included dissatisfaction with salary, the demands of nursing work, the inconvenience of shift work/working hours and uncertain work status. CONCLUSIONS: Findings illustrate that there were several factors influencing the young nurses' intentions. By identifying the factors responsible, it could be possible to retain young nurses in the field. PMID- 17280675 TI - Glycoprotein 63 (gp63) genes show gene conversion and reveal the evolution of Old World Leishmania. AB - Species of the subgenus Leishmania (Leishmania) cause the debilitating disease leishmaniasis on four continents. Species grouped within the Leishmania donovani complex cause visceral leishmaniasis, a life-threatening disease, often associated with poverty, and affecting some 0.5 million people each year. The Leishmania glycoprotein GP63, or major surface protease, is a metalloprotease involved in parasite survival, infectivity and virulence. Here, we show that evolution of the gp63 multigene family is influenced by mosaic or fragmental gene conversion. This is a major evolutionary force for both homogenisation and for generating diversity, even in the absence of sexual reproduction. We propose here that the high GC content at the third codon position in the gp63 family of Old World Leishmania may be higher in multicopy regions, under the biased gene conversion model, because increased copy numbers may lead to increased rates of recombination. We confirm that one class of gp63 genes with an extended 3'end signal, gp63(EXT), reveals genetic groups within the complex and gives insights into evolution and host associations. Gp63(EXT) genes can also provide the basis for rapid and reliable genotyping of strains in the L. donovani complex. Our results confirmed that a more stringent definition of Leishmania infantum is required and that the species Leishmania archibaldi should be suppressed. PMID- 17280676 TI - Delayed parasite elimination in human infections treated with clindamycin parallels 'delayed death' of Plasmodium falciparum in vitro. AB - Clindamycin is safe and effective for the treatment of Plasmodium falciparum malaria, but its use as monotherapy is limited by unacceptably slow initial clinical response rates. To investigate whether the protracted action is due to an accumulative, time of exposure-dependent or a delayed effect on parasite growth, we studied the in vivo and in vitro pharmacodynamic profiles of clindamycin against P. falciparum. In vivo, elimination of young, circulating asexual parasite stages during treatment with clindamycin displayed an unusual biphasic kinetic: a plateau phase was followed by a precipitated decline of asexual parasite densities to nearly undetectable levels after 72 and 60 h in adult patients and asymptomatic children, respectively, suggesting an uninhibited capacity to establish a second, but not third, infectious cycle. In vitro, continuous exposure of a laboratory-adapted P. falciparum strain to clindamycin with concentrations of up to 100 microM for two replication cycles (96 h) did not produce inhibitory effects of >50% compared with drug-free controls as measured by the production of P. falciparum histidine-rich protein II (PfHRP2). PfHRP2 production was completely arrested after the second cycle (96-144h) (>10,000-fold decrease of mean half-inhibitory concentrations measured at 96-144h compared to 48-96h). Furthermore, incubation with clindamycin during only the first (0-48h) versus three (0-144h) parasite replication cycles led to comparable inhibition of PfHRP2 production in the third infectious cycle (96-144h) (mean IC(99) of 27 and 22nM, respectively; P=0.2). When parasite cultures were exposed to different concentrations of clindamycin ranging from 50 to 1,000nM for 72h and followed up in an experiment designed to simulate a typical 3-day treatment regimen, parasitaemia was initially suppressed below the microscopic detection threshold. Nonetheless, parasites reappeared in a dose-dependent manner after removal of drug at 72h but not in continuously drug-exposed controls. The delayed, but potent, antimalarial effect of clindamycin appears to be of greatest potential benefit in new combinations of clindamycin with rapidly acting antimalarial combination partners. PMID- 17280678 TI - Effect of rosiglitazone on factors related to endothelial dysfunction in patients with type 2 diabetes mellitus. AB - The effect of the insulin sensitizer rosiglitazone (RSG) on biological markers of endothelial dysfunction in subjects with type 2 diabetes mellitus (T2DM) was investigated in a 12-week, multi-center, randomized, double-blind study. One hundred and thirty-six subjects aged 40-70 years, with FPG > or = 7.0 and < or = 15.0 mmol/l, previously treated with a single oral anti-diabetic agent or diet/exercise, were randomized to RSG 8 mg/day (n=65) or placebo (PBO, n=71). Results revealed that RSG significantly reduced soluble (s)E-selectin by -10.9% (P=0.004) compared with PBO, but did not significantly alter soluble vascular cell adhesion molecule-1 (+0.6%, P=NS). Compared with PBO, RSG also significantly reduced plasminogen activator inhibitor-1 (-36.9%, P<0.001), tissue plasminogen activator antigen (-22.7%, P<0.001), FPG (-2.8 mmol/l, P<0.001), fasting fructosamine (-42.0 mg/dl, P<0.001). Post-prandial AUC(0-4h) for free fatty acids (FFAs) reduced by -6.5 mg/dl*h from baseline (P=0.03), a change that positively and significantly correlated with changes in sE-selectin (r=0.22, P=0.05). The incidence of adverse events was similar in the two groups (RSG: 35.4%; PBO: 40.8%); the majority mild or moderate. These data support the hypothesis that, in patients with T2DM, rosiglitazone has beneficial effects on biological markers of endothelial dysfunction. Improvements in insulin sensitivity and decreases in FFAs may play a role in these effects. PMID- 17280677 TI - Genetic manipulation of schistosomes. AB - In contrast to the situations with model organisms and parasitic protozoa, progress with gene manipulation with schistosomes has been delayed by impediments that include our inability to maintain the life cycle in vitro, absence of immortalized cell lines, large genome sizes, unavailability of drug resistance markers and other difficulties. However, in the past few years, tangible progress has been reported towards development of tools for gene manipulation and transgenesis of schistosomes, and there is reason to believe that the field is on the verge of transformation into an era where genetic manipulation is routine. Recent reports dealing with approaches and tools to manipulate the genome and gene expression in schistosomes are reviewed here. PMID- 17280679 TI - Preparative isolation and purification of bioactive constituents from Aconitum coreanum by high-speed counter-current chromatography coupled with evaporative light scattering detection. AB - Preparative high-speed counter-current chromatography (HSCCC) coupled with evaporative light scattering detection (ELSD) was employed for the isolation and purification of alkaloids from the roots of Aconitum coreanum (Levl.) Rapaics. The two-phase solvent system used in HSCCC was n-hexane-ethyl acetate-methanol 0.2M HCl (1:3.5:2:4.5, v/v/v/v). Six alkaloids were obtained and yielded 10.4 mg of Guanfu base P, 9.2 mg of Guanfu base G, 9.5 mg of Guanfu base F, 8.9 mg of atisine, 11.9 mg of Guanfu base A and 25.7 mg of Guanfu base I from 2 g of crude extracts. The purity of these compounds was 96.9%, 95.7%, 91.5%, 98.9%, 95.8% and 95.5%, respectively, as determined by high-performance liquid chromatography (HPLC). Their chemical structures were identified by MS, (1)H NMR and (13)C NMR. PMID- 17280680 TI - The bandwidth in gradient elution chromatography with a retained organic modifier. AB - The variance of a chromatographic band is derived in the case of RPLC gradient elution when the organic modifier is significantly retained onto the stationary phase. This derivation is based on the extension of a model due to Poppe et al. [H. Poppe, J. Paanakker, M. Bronckhorst, J. Chromatogr., 204 (1981) 77] which assumes that the gradient front remains unchanged and propagates along the column at the same speed as the mobile phase, following piston flow. Theoretical and experimental results are compared in the case of caffeine on a C(1)-silica stationary phase eluted with an acetonitrile gradient. The actual retention behaviors of caffeine and acetonitrile were implemented in the theoretical calculations. The model predicts compression factors between 0.71 and 0.34 for relatively smooth gradient steepness, betat(0), between 0.009 and 0.054 while the corresponding experimental band compression factors vary between 1.01 and 0.43 for the very same gradient steepness. The model underestimation of these factors arises likely from the strong deviation of the actual retention behavior from the prediction of the Linear Solvent Strength Model (LSSM). PMID- 17280681 TI - High-performance liquid chromatography with nuclear magnetic resonance detection applied to organosilicon polymers. Part 2. Comparison with other methods. AB - LC-NMR utilizing (1)H and (29)Si NMR spectroscopy is ideally suited for the analysis of silicones. It is shown that reversed phase gradient LC-NMR surpasses standard gel permeation chromatography (GPC) and diffusion ordered spectroscopy (DOSY) in the analysis of model hydride terminated polydimethylsiloxane. (1)H and (29)Si NMR in the stopped-flow arrangement leads to full identification of the components. Concentration gradient introduces a dependence of the (29)Si shifts on solvent composition, this dependence can be substantially reduced by a proposed method of referencing. It is shown that the ADEQUATE version of powerful but insensitive 2D INADEQUATE experiment can be used for complete line assignment. PMID- 17280682 TI - Myocardial metastases presenting as ventricular tachycardia. PMID- 17280683 TI - Species-dependent serum interference in a sandwich ELISA for Apo2L/TRAIL. AB - To support pre-clinical studies of Apo2L/TRAIL in rodents and non-human primates, a sandwich ELISA was developed using two mouse monoclonal anti-Apo2L/TRAIL antibodies. Mouse, rat, cynomolgus monkey, and chimpanzee serum at concentrations of > or =1% were found to interfere with accurate quantitation of Apo2L/TRAIL. Moreover, the characteristics of the serum interference for each species were different. In order to resolve the observed serum effect, studies were performed in which salts, detergents, and blocking proteins were added to the sample diluent, and optimized sample diluents that eliminated serum interference were developed for mouse, cynomolgus monkey, and chimpanzee serum. These buffers consisted of a base assay diluent (PBS/0.5% BSA/0.05% Tween-20/10 ppm ProClin 300) supplemented with: NaCl (mouse serum); NaCl, EDTA, CHAPS, bovine gamma globulin (BGG), and human IgG (cynomolgus monkey serum); and NaCl and EDTA (chimpanzee serum). Full characterization studies were performed for the "buffer" ELISA run in base assay diluent (intended for non-serum samples) as well as the assays optimized for mouse serum and cynomolgus monkey serum. Precision, accuracy, linearity, and specificity were found to be satisfactory. With the availability of a rabbit polyclonal antibody against Apo2L/TRAIL, a new pAb/mAb ELISA was developed. This assay was not only more sensitive by > or =6-fold, but it was also much less subject to serum interference. PMID- 17280684 TI - An essential role for the DnaK molecular chaperone in stabilizing over-expressed substrate proteins of the bacterial twin-arginine translocation pathway. AB - All secreted proteins in Escherichia coli must be maintained in an export competent state before translocation across the inner membrane. In the case of the Sec pathway, this function is carried out by the dedicated SecB chaperone and the general chaperones DnaK-DnaJ-GrpE and GroEL-GroES, whose job collectively is to render substrate proteins partially or entirely unfolded before engagement of the translocon. To determine whether these or other general molecular chaperones are similarly involved in the translocation of folded proteins through the twin arginine translocation (Tat) system, we screened a collection of E. coli mutant strains for their ability to transport a green fluorescent protein (GFP) reporter through the Tat pathway. We found that the molecular chaperone DnaK was essential for cytoplasmic stability of GFP bearing an N-terminal Tat signal peptide, as well as for numerous other recombinantly expressed endogenous and heterologous Tat substrates. Interestingly, the stability conferred by DnaK did not require a fully functional Tat signal as substrates bearing translocation defective twin lysine substitutions in the consensus Tat motif were equally unstable in the absence of DnaK. These findings were corroborated by crosslinking experiments that revealed an in vivo association between DnaK and a truncated version of the Tat substrate trimethylamine N-oxide reductase (TorA502) bearing an RR or a KK signal peptide. Since TorA502 lacks nine molybdo-cofactor ligands essential for cofactor attachment, the involvement of DnaK is apparently independent of cofactor acquisition. Finally, we show that the stabilizing effects of DnaK can be exploited to increase the expression and translocation of Tat substrates under conditions where the substrate production level exceeds the capacity of the Tat translocase. This latter observation is expected to have important consequences for the use of the Tat system in biotechnology applications where high levels of periplasmic expression are desirable. PMID- 17280686 TI - Effects of passengers on bus driver celeration behavior and incident prediction. AB - PROBLEM: Driver celeration (speed change) behavior of bus drivers has previously been found to predict their traffic incident involvement, but it has also been ascertained that the level of celeration is influenced by the number of passengers carried as well as other traffic density variables. This means that the individual level of celeration is not as well estimated as could be the case. Another hypothesized influence of the number of passengers is that of differential quality of measurements, where high passenger density circumstances are supposed to yield better estimates of the individual driver component of celeration behavior. METHOD: Comparisons were made between different variants of the celeration as predictor of traffic incidents of bus drivers. The number of bus passengers was held constant, and cases identified by their number of passengers per kilometer during measurement were excluded (in 12 samples of repeated measurements). RESULTS: After holding passengers constant, the correlations between celeration behavior and incident record increased very slightly. Also, the selective prediction of incident record of those drivers who had had many passengers when measured increased the correlations even more. CONCLUSIONS: The influence of traffic density variables like the number of passengers have little direct influence on the predictive power of celeration behavior, despite the impact upon absolute celeration level. Selective prediction on the other hand increased correlations substantially. This unusual effect was probably due to how the individual propensity for high or low celeration driving was affected by the number of stops made and general traffic density; differences between drivers in this respect were probably enhanced by the denser traffic, thus creating a better estimate of the theoretical celeration behavior parameter C. The new concept of selective prediction was discussed in terms of making estimates of the systematic differences in quality of the individual driver data. PMID- 17280685 TI - DNA-PK is involved in repairing a transient surge of DNA breaks induced by deceleration of DNA replication. AB - Cells that suffer substantial inhibition of DNA replication halt their cell cycle via a checkpoint response mediated by the PI3 kinases ATM and ATR. It is unclear how cells cope with milder replication insults, which are under the threshold for ATM and ATR activation. A third PI3 kinase, DNA-dependent protein kinase (DNA PK), is also activated following replication inhibition, but the role DNA-PK might play in response to perturbed replication is unclear, since this kinase does not activate the signaling cascades involved in the S-phase checkpoint. Here we report that mild, transient drug-induced perturbation of DNA replication rapidly induced DNA breaks that promptly disappeared in cells that contained a functional DNA-PK whereas such breaks persisted in cells that were deficient in DNA-PK activity. After the initial transient burst of DNA breaks, cells with a functional DNA-PK did not halt replication and continued to synthesize DNA at a slow pace in the presence of replication inhibitors. In contrast, DNA-PK deficient cells subject to low levels of replication inhibition halted cell cycle progression via an ATR-mediated S-phase checkpoint. The ATM kinase was dispensable for the induction of the initial DNA breaks. These observations suggest that DNA-PK is involved in setting a high threshold for the ATR-Chk1 mediated S-phase checkpoint by promptly repairing DNA breaks that appear immediately following inhibition of DNA replication. PMID- 17280687 TI - The evolution of functionally referential meaning in a structured world. AB - Animal communication systems serve to transfer both motivational information- about the intentions or emotional state of the signaler--and referential information--about external objects. Although most animal calls seem to deal primarily with motivational information, those with a substantial referential component are particularly interesting because they invite comparison with words in human language. We present a game-theoretic model of the evolution of communication in a "structured world", where some situations may be more similar to one another than others, and therefore require similar responses. We find that breaking the symmetry in this way creates the possibility for a diverse array of evolutionarily stable communication systems. When the number of signals is limited, as in alarm calling, the system tends to evolve to group together situations which require similar responses. We use this observation to make some predictions about the situations in which primarily motivational or referential communication systems will evolve. PMID- 17280688 TI - Attenuation of 4-nitroquinoline 1-oxide induced in vitro lipid peroxidation by green tea polyphenols. AB - Lipid peroxidation is believed to play an important role in pathogenesis of diseases. 4-Nitroquiunoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, was found to induce lipid peroxidation in vivo and in vitro. Green tea contains high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GP) can play a protective role in 4-NQO induced in vitro lipid peroxidation. 4-NQO at the concentration of 1.5 mM was found to induce lipid peroxidation in 5% liver homogenate in phosphate buffered saline and extent of lipid peroxidation at the different time intervals 0, 15, 30 and 45 min where studied by assessing parameters such as hydroxyl radical production (OH), thiobarbituric acid reactants (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). It was found that addition of 4-NQO caused an increase in OH and TBARS level and a decrease in activity of SOD, CAT and the levels of GSH. Simultaneous addition of GP 10 mg/ml significantly decreased lipid peroxidation and increased in antioxidant status. Thus, we conclude that GP, a potent antioxidant, was found to nullify 4-NQO induced lipid peroxidation in vitro and 4-NQO acts initially by causing oxidative stress and leads to carcinogenesis. PMID- 17280690 TI - Trawling the sea bed (Sheppard, 2006). PMID- 17280689 TI - SLURP-1 and -2 in normal, immortalized and malignant oral keratinocytes. AB - The secreted mammalian Ly-6/urokinase plasminogen activator receptor-related proteins (SLURP)-1 and -2 are produced by keratinocytes comprising the mucocutaneous epithelium. They regulate in autocrine and paracrine ways cell growth and differentiation through the nicotinic acetylcholine receptors (nAChRs) expressed on the plasma membrane. Keratinocyte nAChRs are targeted by tobacco derived carcinogenic nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) that can induce tumorigenic transformation of Het-1A keratinocytes. In this study we asked if SLURPs could abolish tumorigenic effects of nitrosamines. Preincubation with either recombinant SLURP 1 or -2 in both cases considerably reduced the number of colonies in soft agar, and the number of tumor nodules >0.5 cm in diameter in Nu/Nu mice produced by Het 1A cells treated with nitrosamines. The levels of SLURP-1 and -2 mRNA transcripts in nitrosamine-transformed Het-1A cells as well as in the tumor cell lines SCC-25 and FaDu were significantly (p<0.05) less compared to normal gingival keratinocytes, which are probably the major source of the secreted SLURPs found in a sample of human saliva. The expression of SLURPs was decreased due to gene silencing of different nAChR alpha subunits with small hairpin RNA, suggesting that a positive feedback regulation is altered in malignant cells. Thus, SLURP-1 and -2 are efficient autocrine and paracrine ligands of keratinocyte nAChRs capable of preventing tobacco nitrosamine-induced malignant transformation of oral cells. These "proof-of-concept" preliminary results have salient clinical implications. PMID- 17280691 TI - Parietal disruption impairs reflexive spatial attention within and between sensory modalities. AB - Reflexive spatial attention is critical for controlling perception and action. An established body of evidence suggests that mechanisms of spatial attention operate both within and between sensory modalities; however the attentional mechanisms that link modalities in the human brain are unclear. Here we used transcranial magnetic stimulation (TMS) to explore the role of the parietal cortex in coordinating reflexive shifts of spatial attention between vision and touch. In two experiments, healthy participants localised visual and somatosensory targets that were preceded by non-informative visual or somatosensory spatial cues. To determine the role of parietal cortex in spatial orienting, TMS was delivered synchronously with cue onset for 100 ms. Results revealed a critical role of the right angular gyrus and supramarginal gyrus in reflexive orienting to visual and somatosensory targets that followed a somatosensory cue. In contrast, the same TMS protocol was ineffective in modulating reflexive orienting based on visual cues. This dependence on cue modality may reflect subcortical redundancy of visual orienting mechanisms. Overall, our results indicate a critical role of the inferior parietal cortex in mediating reflexive shifts of attention within and between sensory modalities. PMID- 17280692 TI - Public health law and tuberculosis control in Europe. AB - BACKGROUND: Tuberculosis control is an important public health challenge in many European countries. Law is an important tool that policy-makers can draw upon to support control efforts and, according to the World Health Organization, represents a tangible expression of political commitment and will. Despite this, little national research, and even less cross-national comparative research, has been conducted to describe and analyse legislative approaches to tuberculosis control. METHODS: We conducted a survey of 14 European countries to identify, describe, map and analyse legislative tools used to support tuberculosis control. RESULTS: We found a wide range of legislative models. Legal measures available to nation states, such as compulsory examination, compulsory screening, compulsory detention, compulsory treatment and compulsory vaccination, vary widely in both scope and number. We identified a typology of legal frameworks, from the most authoritarian to the least restrictive. It seems likely that the application of some laws might not withstand scrutiny under the European Convention for the Protection of Human Rights and Fundamental Freedoms. CONCLUSIONS: Harmonization of legislative response to infectious diseases, based upon sound evidence, may be necessary if collaborative efforts in support of infectious disease control, as envisaged in the new International Health Regulations, are to be most effective and are to reflect more appropriately a globalized 21st century world. PMID- 17280693 TI - Profile of food handlers working in food service establishments located within the premises of a medical college in Delhi, India. AB - OBJECTIVES: To find out: (1) the socio-demographic and professional characteristics of food handlers working in food service establishments located in the campus of a medical college in New Delhi, (2) the prevalence of morbid conditions among them and their health-care-seeking behaviour and immunization status. STUDY DESIGN: Cross-sectional study METHODS: A total of 151 food handlers working in 18 food service establishments were interviewed regarding their socio demographic and professional characteristics, history of substance use, disease if any and health care sought for it, immunization status and pre-placement and in-service medical examination. They were also subjected to clinical examination. Stool examination was done for 129 study subjects. RESULTS: The majority were less than 40 years of age (60.3%), male (97.4%), Hindu (95.3%), literate (80.1%) and had the habit of substance use (75.5%). Most of them (94.7%) had one or more morbid conditions, important ones being dental caries (50.3%), worm infestation (41.1%) and injuries/burns on hands (39.7%). The health seeking behaviour, immunization status in relation to enteric group of fevers and tetanus and pre placement and in-service medical examination were observed to be unsatisfactory. CONCLUSION: The findings of the study highlight the need of creating awareness among food handlers about various measures of maintaining food hygiene and ensuring their good health through pre-placement and inservice medical examination. PMID- 17280694 TI - CoMSIA and docking study of rhenium based estrogen receptor ligand analogs. AB - OPLS all atom force field parameters were developed in order to model a diverse set of novel rhenium based estrogen receptor ligands whose relative binding affinities (RBA) to the estrogen receptor alpha isoform (ERalpha) with respect to 17beta-estradiol were available. The binding properties of these novel rhenium based organometallic complexes were studied with a combination of Comparative Molecular Similarity Indices Analysis (CoMSIA) and docking. A total of 29 estrogen receptor ligands consisting of 11 rhenium complexes and 18 organic ligands were docked inside the ligand-binding domain (LBD) of ERalpha utilizing the program Gold. The top ranked pose was used to construct CoMSIA models from a training set of 22 of the estrogen receptor ligands which were selected at random. In addition scoring functions from the docking runs and the polar volume (PV) were also studied to investigate their ability to predict RBA ERalpha. A partial least-squares analysis consisting of the CoMSIA steric, electrostatic and hydrophobic indices together with the polar volume proved sufficiently predictive having a correlation coefficient, r(2), of 0.94 and a cross-validated correlation coefficient, q(2), utilizing the leave-one-out method of 0.68. Analysis of the scoring functions from Gold showed particularly poor correlation to RBA ERalpha which did not improve when the rhenium complexes were extracted to leave the organic ligands. The combined CoMSIA and polar volume model ranked correctly the ligands in order of increasing RBA ERalpha, illustrating the utility of this method as a prescreening tool in the development of novel rhenium based estrogen receptor ligands. PMID- 17280695 TI - Geminivirus pathogenicity protein C4 interacts with Arabidopsis thaliana shaggy related protein kinase AtSKeta, a component of the brassinosteroid signalling pathway. AB - Beet curly top virus (BCTV) C4 interacted with two members of the shaggy-related protein kinase family (AtSKeta and AtSKzeta) and a putative leucine-rich repeat receptor-like kinase (LRR-RLK) in a yeast two-hybrid assay. Tomato golden mosaic virus (TGMV) AC4 also bound with similar efficiency to AtSKeta and AtSKzeta but was unable to interact with the LRR-RLK. BCTV C4 interaction with AtSKeta was confirmed using an in vitro binding assay. The protein kinases were capable of autophosphorylation in vitro and AtSKeta phosphorylated BCTV C4 at threonine and serine residues. AtSKeta phosphorylation of TGMV AC4 was significantly less efficient. The LRR-RLK did not efficiently phosphorylate BCTV C4. BCTV C4 localisation to the cell periphery in Nicotiana benthamiana was dependent on an intact N-terminal myristoylation motif, consistent with plasma membrane targeting. The intact motif was also required to produce the wild-type disease phenotype. Transient expression of BCTV C4 and TGMV AC4 derivatives in N. benthamiana identified additional amino acids within a central domain that contribute to the phenotype. The interaction with AtSKeta indicates that BCTV C4 interacts with the brassinosteroid signalling pathway. PMID- 17280696 TI - Independent coding of object motion and position revealed by distinct contingent aftereffects. AB - Despite several findings of perceptual asynchronies between object features, it remains unclear whether independent neuronal populations necessarily code these perceptually unbound properties. To examine this, we investigated the binding between an object's spatial frequency and its rotational motion using contingent motion aftereffects (MAE). Subjects adapted to an oscillating grating whose direction of rotation was paired with a high or low spatial frequency pattern. In separate adaptation conditions, we varied the moment when the spatial frequency change occurred relative to the direction reversal. After adapting to one stimulus, subjects made judgments of either the perceived MAE (rotational movement) or the position shift (instantaneous phase rotation) that accompanied the MAE. To null the spatial frequency-contingent MAE, motion reversals had to physically lag changes in spatial frequency during adaptation. To null the position shift that accompanied the MAE, however, no temporal lag between the attributes was required. This demonstrates that perceived motion and position can be perceptually misbound. Indeed, in certain conditions, subjects perceived the test pattern to drift in one direction while its position appeared shifted in the opposite direction. The dissociation between perceived motion and position of the same test pattern, following identical adaptation, demonstrates that distinguishable neural populations code for these object properties. PMID- 17280697 TI - Effect of third-order aberrations on dynamic accommodation. AB - We investigate the potential for the third-order aberrations coma and trefoil to provide a signed cue to accommodation. It is first demonstrated theoretically (with some assumptions) that the point spread function is insensitive to the sign of spherical defocus in the presence of odd-order aberrations. In an experimental investigation, the accommodation response to a sinusoidal change in vergence (1 3D, 0.2Hz) of a monochromatic stimulus was obtained with a dynamic infrared optometer. Measurements were obtained in 10 young visually normal individuals with and without custom contact lenses that induced low and high values of r.m.s. trefoil (0.25, 1.03 microm) and coma (0.34, 0.94 microm). Despite variation between subjects, we did not find any statistically significant increase or decrease in the accommodative gain for low levels of trefoil and coma, although effects approached or reached significance for the high levels of trefoil and coma. Theoretical and experimental results indicate that the presence of Zernike third-order aberrations on the eye does not seem to play a crucial role in the dynamics of the accommodation response. PMID- 17280698 TI - Pressurized CO2/zero valent iron system for nitrate removal. AB - A fluidized zero valent iron (ZVI) reactor pressurized by CO(2) gas for controlling pH was employed for nitrate reduction. The proposed CO(2) pressurized system potentially has advantages of using less CO(2) gas and reaching equilibrium pH faster than CO(2)-bubbled system. However, due to weak acid nature of carbonic acid, system pH gradually increased with increasing oxidation of ZVI and reduction of nitrate. As pH increased with progress of reaction, nitrate removal rate decreased continuously. The results indicate that nitrate removal efficiency increases with increasing initial ZVI dosage but reaches plateau at ZVI doses of higher than 8.25gl(-1), and initial nitrate concentration up to 100mg l(-1) as N has minimal impact on the removal efficiency. Unlike the fluidized system with pH control by strong acid reported in our pervious study, near 100% of nitrogen recovery was observed in the current process, indicating that nitrate reduction by ZVI with different pH controlled mechanisms will have different reaction routes. PMID- 17280699 TI - Application of Markov model to environmental fate of phenanthrene in Lanzhou Reach of Yellow River. AB - The theory of Markov Chain is used scientifically to describe the transfer/transformation of phenanthrene in Lanzhou Reach of Yellow River. In Markov Model (MM), the states of phenanthrene in Lanzhou Reach are divided into six different states, namely being degraded, leaving the system with the addvective flow, being in air, being in water, being adsorbed on suspending substances (SS), and being in bottom sediment (BS). The MM is simulated by using Matlab6.5 to reveal the temporal changes and environmental fate of phenanthrene in Lanzhou Reach. It is shown that the environmental system will be steady in 30,000-35,000 h, the final distributions of phenanthrene in air, water, SS, and BS are 23,033 kg, 1961 kg, 800 kg, and 2824 kg respectively, with the corresponding percent of 80%, 7%, 3%, and 10%. The results of MM are approximate to the results of Fugacity Model (FM), so Markov Chain can be used to evaluate the environmental fate of pollutants in multimedia environment. The outputs of MM include the following aspects: (1) The residual time of pollutant in different environmental media and the transiting time of pollutant between different environmental media; (2) The response time of the environmental system; (3) The total mass of pollutant transferred or degraded during a given time interval; (4) The time needed for the environmental system to be steady and the final steady distributions of pollutant in the environmental system. PMID- 17280700 TI - Uptake and accumulation of cadmium, lead and zinc by Siam weed [Chromolaena odorata (L.) King & Robinson]. AB - The Siam weed, Chromolaena odorata (L.) King & Robinson, Family Asteraceae, was found to be a new Pb hyperaccumulator by means of field surveys on Pb soil and hydroponic studies. Plants from field collection accumulated 1377 and 4236mgkg( 1) Pb in their shoots and roots, respectively, and could tolerate soil Pb concentrations up to 100000 mgkg(-1) with a translocation factor of 7.62. Very low concentrations of Cd and Zn were found in plants collected from the field. Under nutrient solution culture condition, C. odorata from the contaminated site (CS) and from non-contaminated site (NCS) grew normally with all three metals (Pb, Cd, Zn) supplied. However, the relative growth rates of all treated plants decreased with increased metal concentrations. The percentage uptakes of Pb, Cd, and Zn by C. odorata increased with increasing metal concentrations. Pb concentration in shoots and roots reached its highest values (1772.3 and 60655.7mgkg(-1), respectively) at a Pb supply level of 10mgl(-1). While the maximum concentrations of Cd (0.5mgl(-1)) in shoots and roots of C. odorata were 102.3 and 1440.9mgkg(-1), and the highest concentrations of Zn (20mgl(-1)) were 1876.0 and 7011.8mgkg(-1), respectively. The bioaccumulation coefficients of Pb and Cd were greater than 1000. These results confirm that C. odorata is a hyperaccumulator which grows rapidly, has substantial biomass, wide distribution and has a potential for the phytoremediation of metal contaminated soils. PMID- 17280701 TI - Photolysis of nonylphenol ethoxylates: the determination of the degradation kinetics and the intermediate products. AB - The photolysis of nonylphenol ethoxylates with an average oligomers length of ten ethoxylate units (NPEO(10)) in aqueous solution under UV, as well as the influence of humic acid (HA) on the photolysis was studied. A 125W high-pressure mercury lamp was employed as the light source. The intermediate products from the photolysis were determined by LC-MS. The results indicated that NPEO(10) underwent direct photolysis upon exposed to UV. The degradation pathway was complex. Besides the generally proposed degradation pathway of ethylene oxide (EO) side chains shortening, the oxidation of alkyl chain and EO chain led to intermediates having both a carboxylated (as well as carbonylated) ethoxylate and alkyl chain of varying lengths. The hydrogenation of benzene ring was also detected. The kinetics data showed that the first order reaction kinetics could be well used to describe the kinetics of NPEO(10) degradation. In the presence of dissolved organic matter by HA addition, the performance of NPEO(10) photodegradation was reduced. The photolysis rate decreased with increased HA concentration. PMID- 17280702 TI - Effect of pre-treatment and supporting media on Ni(II), Cu(II), Al(III) and Fe(III) sorption by plant root material. AB - In this work Paspalum notatum root material was used to elucidate the influence of acid leaching pre-treatment and of sorption medium on metal adsorption. Ground P. notatum root was leached with 0.14M HNO(3). Leached root material (LRM) and non-leached root material (NLRM) were employed to flow sorption of Ni(II), Cu(II), Al(III) and Fe(III) in 0.5M CH(3)COONH(4) medium at pH 6.5. For LRM the sorption was also studied in 0.5M KNO(3) medium. The acid pre-treatment increased the sorption capacity (SC) for all ions studied. For the KNO(3) medium, Cu(II) and Fe(III) sorption was higher than in CH(3)COONH(4) and the type of the Ni(II) isotherm's model changed. The Freundlich model was the most representative isotherm model to describe metallic ions sorption. The (1)H NMR spectra showed differences between LRM and NLRM and the acid-basic potentiometric titration elucidated that acid-leaching procedure affected the root material sorption sites once only two predominant sorption sites were found for LRM (phenolic and amine, both able cations sorption) and five sorption sites (two carboxylic, amine and two phenolic) were founded for NLRM. PMID- 17280703 TI - Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in breast milk from the Pacific Northwest. AB - Breast milk samples from 40 first-time mothers from the Pacific Northwest of the US and Canada were analyzed for polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs). Total PBDEs (summation operator PBDEs), calculated by summing values for the 12 PBDEs congeners analyzed, ranged from 6 to 321 ppb (lipid weight) (mean=96 ppb; median=50 ppb). In approximately 40% of the women (15/40), summation operator PBDEs>100 ppb lw in their milk, and four samples had levels >250 ppb lw. PBDE 47 was the dominant congener in most samples, whereas PBDE 153 was predominant in a few (3/40). summation operator PCBs were calculated by summing values for the 82 PCB congeners analyzed, and ranged from 49 to 415 ppb (lipid weight) (mean=147 ppb; median=126 ppb). approximately 30% of the mothers (13/40) have summation operator PBDEs> summation operator PCBs in their milk samples, and approximately 65% (25/40) have BDE 47>PCB 153 in breast milk samples, with BDE 47 averaging 3-fold greater levels than PCB 153. Clearly, the lower brominated PBDEs are surpassing PCBs as a major environmental concern in North America, and are likely affecting significant portions of the populations in these regions. PBDEs have become a major persistent organic pollutant. However, there are no positive correlations between levels of summation operator PBDEs and summation operator PCBs, or between levels of PBDE 47 and PCB 153, suggesting there may be some differences in exposure pathways for PBDEs and PCBs in humans. PMID- 17280704 TI - Combination of ozonation with conventional aerobic oxidation for distillery wastewater treatment. AB - Laboratory-scale experiments were conducted in order to investigate the effect of ozone as pre-aerobic treatment and post-aerobic treatment for the treatment of the distillery wastewater. The degradation of the pollutants present in distillery spent wash was carried out by ozonation, aerobic biological degradation processes alone and by using the combinations of these two processes to investigate the synergism between the two modes of wastewater treatment and with the aim of reducing the overall treatment costs. Pollutant removal efficiency was followed by means of global parameters directly related to the concentration of organic compounds in those effluents: chemical oxygen demand (COD) and the color removal efficiency in terms of absorbance of the sample at 254 nm. Ozone was found to be effective in bringing down the COD (up to 27%) during the pretreatment step itself. In the combined process, pretreatment of the effluent led to enhanced rates of subsequent biological oxidation step, almost 2.5 times increase in the initial oxidation rate has been observed. Post-aerobic treatment with ozone led to further removal of COD along with the complete discoloration of the effluent. The integrated process (ozone-aerobic oxidation ozone) achieved approximately 79% COD reduction along with discoloration of the effluent sample as compared to 34.9% COD reduction for non-ozonated sample, over a similar treatment period. PMID- 17280706 TI - Effect of clomazone herbicide on biochemical and histological aspects of silver catfish (Rhamdia quelen) and recovery pattern. AB - The effects of the herbicide, clomazone, on acetylcholinesterase (AChE), catalase and TBARS formation in teleost fish (Rhamdia quelen) were studied. The fish were exposed to 0.5 or 1.0 mg L(-1) of clomazone for 12, 24, 48, 96 and 192 h. After 192 h of exposure period, fish were transferred to clean water and kept in the same for 192 h to study the recovery response. Same parameters as that of exposure period were assayed after 96 and 192 h of recovery period. Specific AChE activity was reduced in the brain and muscle after treatments, reaching a maximum inhibition of 47% in the brain and 45% in the muscle after 12h of exposure. Fish exposed to clomazone increased TBARS production in the liver for all exposure periods. The brain presented elevated TBARS levels after 12, 24 and 48 h, but after 96 and 192 h, these levels decreased. The decrease of TBARS levels persisted in brain tissue after 96 h of recovery and returned to the control value after 192 h in clean water. Catalase activity was reduced for all periods of exposure. Histological analysis showed vacuolation in the liver after herbicide exposure. Some of the alterations observed were completely restored after recovery period. PMID- 17280705 TI - Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) in the serum of US Air Force veterans in 2002. AB - We measured levels of PCDDs, PCDFs, non-ortho, and mono-ortho substituted PCBs in 106 US Air Force Vietnam veterans, participants of the Air Force Health Study (AFHS) who attended the final medical examination in 2002. Twelve veterans were Ranch Hands involved in aerial spraying of herbicides in Vietnam (1962-1971), and 94 were Comparisons who flew transport missions in Southeast Asia (SEA) during the same time period. These veterans had no previous 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) measurement because they had not attended any of the previous AFHS examinations, or their previous measurements were missing or not valid. The mean TCDD levels in 2002 were 1.7 pg/g lipid in Comparisons and 5.5 pg/g lipid in Ranch Hands. The mean PCDD toxic equivalent - TEQ (1997) in Comparisons was 12.6 pg/g lipid, 5.4 pg/g lipid for PCDFs, 5.2 pg/g lipid for non-ortho PCBs, and 9.4 pg/g lipid for mono-ortho PCBs, with a total mean TEQ (1997) of 32.6 pg/g lipid. Corresponding mean TEQs in Ranch Hands were 15.5 pg/g lipid for PCDDs, 4.6 pg/g lipid for PCDFs, 2.2 pg/g lipid for non-ortho PCBs, and 9.3 pg/g lipid for mono ortho PCBs, yielding the total mean TEQ (1997) of 31.6pg/g lipid. Using the re evaluated 2005 WHO TEFs, the total mean TEQs (2005) decreased by about 28% in both Comparisons and Ranch Hands, to 23.6 pg/g lipid and 22.8 pg/g lipid, respectively. This was mainly due to changes of TEFs for the group of mono-ortho PCBs, which decreased the mono-ortho PCBs TEQs by almost 90% in both Ranch Hands and Comparisons. PMID- 17280707 TI - Distribution of polycyclic aromatic hydrocarbons in water, suspended particulate matter and sediment from Daliao River watershed, China. AB - This study investigated the spatial distribution of polycyclic aromatic hydrocarbons (PAHs) in surface water, suspended particulate matter (SPM) and sediment of Daliao River watershed composed of the Hun River, Taizi River, and Daliao River. The sources of PAHs were evaluated employing ratios of specific PAHs compounds and principal component analysis (PCA). The total concentrations of PAHs ranged from 946.1 to 13448.5 ng l(-1) in surface water, from 317.5 to 238518.7 ng g(-1) dry weight in SPM, and from 61.9 to 840.5 ng g(-1) dry weight in sediments. The levels of PAHs are relatively higher in water and SPM, and lower in sediments, in comparison with those reported for other rivers and marine systems around the world. The composition of PAHs in these mediums was mainly 4-6 rings PAHs. The higher contents of low molecular weight PAHs in the water and SPM suggest a relatively recent local source of PAHs, entered into the river via wastewater discharge and atmospheric way. On the other hand, the heavy pollution of PAHs in sediment and water near heavy industrial area suggests that PAHs have been released from industrial wastewater. PMID- 17280708 TI - The influence of EDDS and EDTA on the uptake of heavy metals of Cd and Cu from soil with tobacco Nicotiana tabacum. AB - Phytoextraction, the use of plants to extract contaminants from soils and groundwater, is a promising approach for cleaning up soils contaminated with heavy metals. In order to enhance phytoextraction the use of chelating agents has been proposed. This study aims to assess whether ethylene diamine disuccinate (EDDS), a biodegradable chelator, can be used for enhanced phytoextraction purposed, as an alternative to ethylene diamine tetraacetate (EDTA). EDDS revealed a higher toxicity to tobacco (Nicotiana tabacum) in comparison to EDTA, but no toxicity to microorganisms. The uptake of Cu was increased by the addition of EDTA and EDDS, while no increase was observed in the uptake of Cd. Both chelating agents showed a very low root to shoot translocation capability and the translocation factor was lower than the one of the control. Heavy metals where significantly more phytoavailable than in the control, even after harvesting, resulting in a high heavy metal leaching possibility, probably owing to a low biodegradation rate of EDDS. New seedlings which were transplanted into the EDDS treated pots 7d after the phytoextraction experiment, showed signs of necrosis and chlorosis, which resulted in a significantly lower biomass in comparison to the control. The seedlings on the EDTA treated pots showed no toxicity signs. Contrary to previous opinions the results of this study revealed the chelating agents EDTA and EDDS as unsuitable for enhanced phytoextraction using tobacco. PMID- 17280709 TI - Uptake and localization of gaseous phenol and p-cresol in plant leaves. AB - Understanding foliar uptake processes for organic air pollutants is critical to predicting the fate of these compounds, including their entry into the food chain and their susceptibility to plant-, microbe-, and light-mediated degradation. We characterized the uptake kinetics for gaseous phenol and p-cresol into the leaves of maize seedlings in a closed system over periods up to 23h. When leaves were exposed to mixtures of phenol and p-cresol (3-50microg l(-1) each), the air concentrations of the compounds rapidly decreased, showing residence times of 4 6h. The stomata of the leaves were mostly or completely closed, suggesting that uptake was primarily through the cuticle. The involvement of a cuticular uptake pathway was confirmed based on increased uptake into two cuticular mutants of maize. Models of the uptake data suggested that, at the concentrations used, phenol and p-cresol were taken up in a biphasic manner, consistent with previous two-compartment models for foliar uptake of lipophilic compounds via a cuticular pathway. These models also indicated that phenol was taken up at a slightly faster rate than p-cresol. To begin to understand the fate of these compounds, we examined the location of (14)C in leaves exposed to (14)C-phenol. Significantly more (14)C accumulated in the terminal centimeter than in the central and basal regions of the leaves on both a mass and area basis. This is the first demonstration that a gaseous organic compound, or its breakdown products, accumulates in a spatially non-uniform manner in leaves following foliar uptake. These findings support a role for plants as natural, or deliberate, attenuators of airborne pollutants, and suggest potential availability of these compounds to the leaf surface microflora. PMID- 17280710 TI - Ultrasonic transit-time measurement of blood flow in the umbilical arteries and veins in the bovine fetus during stage II of labor. AB - The vitality of the bovine fetus during parturition depends on an intact umbilical circulation to supply adequate amounts of oxygen and nutrients to the fetus. The goal of the present study was to measure the blood flow in the umbilical vessels during stage II of labor and to determine when blood flow ceases in the umbilical cord. In 20 cows, ultrasonographic transducers were placed on one umbilical vein and one umbilical artery after rupture of the allantochorionic sac, and the blood flow volume per unit time was measured. At the same time, a pressure transducer was placed into the uterus to measure uterine pressure. Parturition was spontaneous in all 20 cows. In 20 live calves born, pH, base excess and lactate concentration were measured in the blood immediately after birth. During the last 90 min before birth the mean total umbilical blood flow (artery and vein combined) was 1.186+/-0.028 L/min. Calves with a blood pH> or =7.2 (n=13) had a higher mean total blood flow than calves with a pH<7.2 (n=7; 1.243+/-0.038 versus 1.095+/-0.038 L/min). In calves with a blood pH<7.2, the mean total blood flow decreased from 1.178+/-0.134 at 20 min before birth to 0.959+/-0.126 L/min at the end of stage II of labor. During this time period, the arterial blood flow did not differ between calves with a blood pH> or =7.2 and<7.2, but venous blood flow decreased significantly in calves with a blood pH<7.2. During uterine contractions, the total umbilical blood flow decreased significantly by 0.22 L/min. The blood flow in the umbilical artery and vein ceased before the calves were completely born. PMID- 17280712 TI - Depuration dynamics of oysters (Crassostrea gigas) artificially contaminated by Salmonella enterica serovar Typhimurium. AB - The State of Santa Catarina produces the greatest quantity of edible mollusks in Brazil. To guarantee sanitary qualify, mollusk cultures should be monitored for contamination by pathogenic microorganisms. A self-purification or "depuration" system that eliminates Salmonella enterica serovar Typhimurium contamination from oysters has been developed and evaluated. The depuration process occurred within a closed system, in which 1000 L of water was recirculated for 24 h. The water was sterilized with ultraviolet (UV) light, chlorine, or both together. Oysters (Crassostrea gigas) artificially contaminated with S. typhimurium were harvested every 6 h. Samples of oyster tissue were excised and both the presence and numbers of bacteria were determined. Combined UV light and chlorine treatments resulted in total elimination of bacteria within 12 h. Polymerase chain reaction detected bacteria in water exposed to the three treatments. This pioneering study is the first of its kind in Brazil and represents a major contribution to commercial mollusk culture in this country. PMID- 17280711 TI - The influence of trehalose, taurine, cysteamine and hyaluronan on ram semen Microscopic and oxidative stress parameters after freeze-thawing process. AB - There is a lack of information regarding lipid peroxidation and antioxidant capacity in cryopreserved ram semen, and cryopreservation is associated with the production of reactive oxygen species (ROS) which lead to lipid peroxidation (LPO) of sperm membranes, resulting in a loss of motility, viability and fertility of sperm. The aim of this study was to determine the influence of certain additives and their different doses on standard semen parameters, lipid peroxidation and antioxidant activities after the cryopreservation/thawing of ram semen. Ejaculates collected from four Akkaraman rams, a native breed of sheep, were evaluated and pooled at 33 degrees C. Semen samples which were diluted with a Tris-based extender containing additives including trehalose (50, 100mM), taurine (25, 50mM), cysteamine (5, 10mM), and hyaluronan (0.5, 1mg/ml), and an extender containing no additives (control) were cooled to 5 degrees C and frozen in 0.25ml French straws, being stored in liquid nitrogen. Frozen straws were thawed individually at 37 degrees C for 20s in a water bath for evaluation. The use of a Tris-based extender supplemented with 50mM trehalose, 25mM taurine, and 5 and 10mM cysteamine led to higher percentages of post-thaw motility, in comparison to the control group (P<0.01). No significant differences were observed in the percentages of acrosome and total abnormalities, and the hypoosmotic swelling test upon the supplementation of the freezing extender with antioxidants after the thawing of semen. In biochemical assays, the addition of antioxidants did not cause significant differences in levels of malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GSH-Px), after thawing, when compared to groups with no additives. In this study, catalase (CAT) activities were higher in the group that was applied 25mM taurine as an antioxidant, than in all of the other groups (P<0.001). Compared to the controls, antioxidant treatment with 100mM trehalose, 50mM taurine, 5mM cysteamine and 0.5mg/ml hyaluronan, significantly elevated vitamin E (vit E) levels in samples (P<0.001). PMID- 17280713 TI - Origin and characteristics of the zooplankton phosphatase activity in a coastal ecosystem of the Mediterranean sea (Toulon Bay). AB - In Toulon Bay (France), very high phosphatase activities have been found in the zooplankton fraction>90 microm. This work was intended to specify their origin. For that purpose, larvae, juvenile and adult Crustacea (Copepods: Calanoids, Cyclopoids, Branchiopods: Cladocera, and Cirripeds) were isolated. Their activities were measured using paranitrophenyl phosphate dissolved in sea water in order to calculate Km (the enzyme half saturation concentration) and Vmax (the reaction rate when the enzyme is saturated with substrate). Vmax were referred to protein contents of the isolated organisms to calculate specific activities. For all zooplankton groups high and low affinity phosphatase activities were found. The low affinity enzyme was responsible for at least 70% of the total phosphatase activity. Its specific activity was higher for larvae than for copepodites and adults. In Cirriped nauplii this activity was particularly high with values which were several hundred times higher than that in other Crustacea. These enzymes had optimum pH close to 8.4, magnesium requirement and were competitively inhibited by orthophosphate. Experiments with intact and lysed Cirriped nauplii confirmed that living organisms had only a weak external activity and showed that most of the activity of these larvae was primarily intracellular. PMID- 17280715 TI - Unusual association of MLL rearrangement and secondary myelomonocytic leukemia in a 15-year-old patient treated for osteosarcoma. PMID- 17280714 TI - Biomechanical and biochemical characteristics of a human fibroblast-produced and remodeled matrix. AB - We report on a culture method for the rapid production of a strong and thick natural matrix by human cells for tissue engineering applications. Dermal fibroblasts were cultured for three weeks at high density on porous substrates in serum-containing or chemically defined media. The mechanical and biochemical properties of the resulting cell-derived matrix (CDM) were compared to those of standard fibroblast-populated collagen and fibrin gels and native human skin. We found that the ultimate tensile strength of CDM cultured in our chemically defined media (313+/-8.7 kPa) is significantly greater than for collagen gels (168+/-39.3 kPa), fibrin gels (133+/-8.0 kPa) and CDM cultured with serum (223+/ 9.0 kPa), but less than native skin (713+/-55.2 kPa). In addition to the biomechanics, this *CDM is also biochemically more similar to native skin than the collagen and fibrin gels in terms of all parameters measured. As *CDM is produced by human cells in a chemically defined culture medium and is mechanically robust, it may be a viable living tissue equivalent for many connective tissue replacement applications requiring initial mechanical stability yet a high degree of biocompatibility. PMID- 17280716 TI - In ovum exposure to pesticides increases the egg weight loss and decreases hatchlings weight of Caiman latirostris (Crocodylia: Alligatoridae). AB - The increasing use of pesticides affects ecosystem health. Caiman latirostris is a South American species with ecological and physiological features that render it vulnerable to exposure to pesticides with endocrine disruptor's action. Our main objective was to test the effect of in ovum exposure to atrazine and endosulfan on the sex ratio of caiman hatchlings; however, we are also presenting unexpected findings regarding pesticide effects on egg weight loss during incubation and hatchlings relative weight. Caiman eggs were incubated under controlled temperature (30 and 33 degrees C) and humidity (>90%). They were treated with vehicle, 17 beta-estradiol (1.4ppm), atrazine (0.2ppm) and endosulfan (0.02; 2; 20ppm). Pesticides did not cause estrogen-like effects on sex determination. Greater egg weight loss was observed in eggs treated with atrazine and higher doses of endosulfan (2 and 20ppm) (p=0.0005). These pesticides also caused a reduction in hatchling fractional weight (p=0.0497). These effects might have a significant impact on caiman population dynamics. PMID- 17280717 TI - Photoacoustic characterization of protein dynamics following CO photodetachment from fully reduced bovine cytochrome c oxidase. AB - We report a protein conformational change following carbon monoxide photodetachment from fully reduced bovine cytochrome c oxidase that is hypothesized to be associated with changes in ligand mobility through a dioxygen access channel in the protein. Although not resolved by earlier photoacoustic or optical studies on this adduct, utilization of slightly lower temperatures revealed a process with a kinetic lifetime of about 70 ns at 10 degrees C. We measure an enthalpy change of about 8 kcal/mol in 0.050 M HEPES buffer that becomes less endothermic (DeltaH approximately 2 kcal/mol) at higher ionic strength. The volume contraction of about -0.7 mL/mol associated with the process almost doubles in higher ionic strength buffer systems. Measurements of samples in phosphate buffer systems are similar and appear to display the same subtle ionic strength dependence. Both the isolation of this photoacoustic signal component and the possible dependence on ionic strength of the thermodynamic parameters derived from its analysis appear analogous to and consistent with prior photoacoustic results monitoring CO photodetachment from the camphor complex of cytochrome P-450. Accordingly, we consider a similar model in which a conformational change results in movement of an exposed charged group or groups towards the interior of the protein, out of contact with solvent, as in the closing of a salt bridge. PMID- 17280718 TI - Identification of the region 285-309 of follicle stimulating hormone receptor as a bioneutralizing epitope. AB - Structure-function relationship studies of the follicle stimulating hormone and its receptor assume importance as this hormone is essential for folliculogenesis and spermatogenesis in females and males, respectively. The interaction between the hormone and the receptor is complex and not well understood. In vitro studies using synthetic peptides from the extracellular domain of the receptor and corresponding antipeptide antibodies have suggested that the 285-309 region is surface-oriented. Antipeptide antibodies to this region also inhibit hormone receptor interaction in a dose-dependent manner and the mechanism of inhibition appears to be competitive in nature. To test this hypothesis in an animal model, antibodies to peptide 285-309 from rat follicle stimulating hormone receptor (FSHR) were developed and characterized. These antibodies were able to detect FSHR in rat ovaries by immunohistochemistry. Further, these antibodies were administered into adult female rats and their effect on fertility status was monitored. These antibodies were found to neutralize the biological activity of endogenous receptor, which resulted in the induction of infertility in the treated animals. Thus, bioneutralization of FSHR has been achieved by targeting its region 285-309 in an in vivo system. PMID- 17280719 TI - An analysis of the incidence of adenoid hypertrophy in allergic children. AB - INTRODUCTION: The adenoidectomy is the most often made operation in small children but the reasons of adenoid hypertrophy are not completely explained. Some researches show that in part of children, allergy can be a risk factor for adenoid hypertrophy. The main aim of this study was the analysis of adenoid hypertrophy in children with different allergic diseases. MATERIAL AND METHODS: Two separate groups of children were examined. The study group consisted of 436 children between 4 and 9 years old with allergic rhinitis and/or bronchial asthma and/or atopic dermatitis hypersensitive to house dust mites (interview, positive skin-prick test results). The control group consisted of 229 non-atopic children (negative interview and skin-prick tests) in the similar age. In the both groups we examined the incidence of adenoid hypertrophy and its dependence of the kind of allergic disease, age, sex, infections, results of skin-prick test and other sensitization. RESULTS: The probability of adenoid hypertrophy was statistically more significant (logistic regression analysis) only in children from the study group with allergic rhinitis. There were no differences in adenoid hypertrophy incidence between children with other allergic diseases and the control group. The children from the study group with adenoid hypertrophy were more often hypersensitive to pollen and moulds allergens than the children without adenoid hypertrophy (chi square test). But there were no differences in the incidence of infection, age, sex and results of skin-prick tests. CONCLUSION: The result of our study suggests that the chance of adenoid hypertrophy in allergic children hypersensitive to dust mites is greater only in them with allergic rhinitis. PMID- 17280720 TI - Neoceptors: reengineering GPCRs to recognize tailored ligands. AB - Efforts to model and reengineer the putative binding sites of G-protein-coupled receptors (GPCRs) have led to an approach that combines small-molecule 'classical' medicinal chemistry and gene therapy. In this approach, complementary structural changes (e.g. based on novel ionic or H-bonds) are made in the receptor and ligand for the selective enhancement of affinity. Thus, a modified receptor (neoceptor) is designed for activation by tailor-made agonists that do not interact with the native receptor. The neoceptor is no longer activated by the native agonist, but rather functions as a scaffold for the docking of novel small molecules (neoligands). In theory, the approach could verify the accuracy of GPCR molecular modeling, the investigation of signaling, the design of small molecules to rescue disease-related mutations, and small-molecule-directed gene therapy. The neoceptor-neoligand pairing could offer spatial specificity by delivering the neoceptor to a target site, and temporal specificity by administering neoligand when needed. PMID- 17280721 TI - Learning from the past: evolution of GPCR functions. AB - Classical methods have been recruited to determine the molecular function and the physiological relevance of G-protein-coupled receptors (GPCRs), including ligand binding and signal transduction studies, pharmacological receptor profiling in tissues and the characterization of transgenic mouse models. Evolutionary data from both sequenced genomes and targeted retrieved orthologs are increasingly used as a source of structural information. Recent success in sequencing and functionally expressing GPCRs from fossils opens the possibility of studying signaling pathways even in extinct species. Therefore, mining evolutionary data provides an additional source for understanding the functional relevance of individual GPCRs, for interpreting naturally occurring receptor mutations in patients and for guiding structural modeling and mutagenesis studies of GPCRs. PMID- 17280722 TI - Detection of Banana mild mosaic virus and Banana virus X by polyvalent degenerate oligonucleotide RT-PCR (PDO-RT-PCR). AB - Viruses are important constraints to the movement and propagation of plant germplasm, especially for vegetatively propagated crops such as banana and plantain. Their control relies primarily on the use of virus-free plant material, whose production and certification requires sensitive and reliable detection methods. An existing polyvalent degenerate oligonucleotide RT-PCR (PDO-RT-PCR) assay was adapted to the detection of Banana mild mosaic virus (BanMMV) and Banana virus X, two Flexiviridae infecting Musa spp. PDO inosine-containing primers were found to be well suited to the detection of BanMMV, despite its high molecular diversity, but not to that of the highly conserved BVX, for which species-specific primers were designed. Sampling and sample processing steps were optimized in order to avoid nucleic acid purification prior to the reverse transcription step. A polyclonal anti-BanMMV antiserum was raised and successfully used for the immunocapture (IC) of BanMMV viral particles from leaf extracts, leading to the development of a PDO-IC-RT-nested PCR assay. Although the anti-BanMMV antiserum could to some extent recognize BVX viral particles, direct binding (DB) was shown to be a more efficient method for processing BVX infected samples and a PDO-DB-RT-nested PCR assay was developed for the detection of BVX from leaf extracts. PMID- 17280724 TI - Whether feeling or seeing is more accurate depends on tracking direction within the perception-action cycle. AB - Coordination in biological systems requires a continuous updating of the perception-action cycle. How the different sources of sensory information contribute uniquely to performance is still debated. Here, we directly compared the role of vision and kinesthesis by means of a tracking task in which the left wrist mimicked the passive motions imposed on the right wrist with a torque motor. The passive movements were perceived visually (alien hand) or kinesthetically (own hand), or a combination thereof (own hand, feel and see). Tracking occurred according to the same (isodirectional) or opposite (mirror image) directions. Findings revealed that visual tracking was performed most successfully in the isodirectional and kinesthetic tracking in the mirror-image mode. Tracking was most successful when both sources of sensory information were present. These results suggest that vision and proprioception obey direction dependent constraints that are consistent with extrinsic and intrinsic reference frames within which the perception-action cycle resides. Thus, each sensory modality contributes uniquely as a function of the spatial requirements of the tracking task, rather than one being superior over the other. PMID- 17280723 TI - Anti-hepatitis B virus activity of wogonin in vitro and in vivo. AB - The traditional Chinese medicine Scutellaria radix has been used for thousands of years, mainly for the treatment of inflammatory conditions including hepatitis. The major active constituent, wogonin (WG), isolated from S. radix has attracted increasing scientific attention in recent years due to its potent biological activities. However, pharmacologic studies have primarily been focused on wogonin's anti-inflammatory and anti-cancer activities. In this study, we have investigated wogonin's anti-hepatitis B virus (HBV) activity both in vitro and in vivo. In the human HBV-transfected liver cell line HepG2.2.15, wogonin effectively suppressed the secretion of the HBV antigens with an IC(50) of 4 microg/ml at day 9 for both HBsAg and HBeAg. Consistent with the HBV antigen reduction, wogonin also reduced HBV DNA level in a dose-dependent manner. Duck hepatitis B virus (DHBV) DNA polymerase was dramatically inhibited by wogonin with an IC(50) of 0.57 microg/ml. In DHBV-infected ducks wogonin dosed i.v. once a day for 10 days reduced plasma DHBV DNA level with an ED(50) of 5mg/kg. The in vivo anti-HBV effect of wogonin in ducks was confirmed by Southern blotting of DHBV DNA in the liver. Histopathological evaluation of the liver revealed significant improvement by wogonin. In addition, in human HBV-transgenic mice, wogonin dosed i.v. once a day for 10 days significantly reduced plasma HBsAg level. Immunohistological staining of the liver confirmed the HBsAg reduction by wogonin. In conclusion, our results demonstrate that wogonin possesses potent anti-HBV activity both in vitro and in vivo. Currently, wogonin is under early development as an anti-HBV drug candidate. PMID- 17280725 TI - Anxiolytic effect of music depends on ovarian steroid in female mice. AB - Music is known to be able to elicit emotional changes, including anxiolytic effects. The gonadal steroid hormones estradiol and progesterone have also been reported to play important roles in the modulation of anxiety. In the present study, we examined whether the effect of music on anxiety is related to ovarian steroid in female mice. Behavioral paradigms measuring anxiety were tested in gonadally intact (SHAM) and ovariectomized (OVX) female mice chronically treated with either placebo (OVX/Placebo), 17beta-estradiol (OVX/E), or progesterone (OVX/P). In the elevated plus maze, light-dark transition, and marble burying tests, SHAM and OVX/P mice exposed to music showed less anxiety than those exposed to white noise or silence while OVX/placebo mice did not show these effects at all. OVX/E mice showed the anxiolytic effect of music only in the marble burying test. Furthermore, pretreatment with progesterone's metabolite inhibitor completely prevented the anxiolytic effect of music in behavioral tests, while pretreatment with a progesterone receptor blocker did not prevent the anxiolytic effect of music. These results suggest that exposure to music reduces anxiety levels, and ovarian steroids, mainly progesterone, may be involved in the anxiolytic effect of music observed in female mice. PMID- 17280726 TI - Effects of intra-nasally administered testosterone on sexual proceptive behavior in female capuchin monkeys (Cebus apella). AB - Sexual dysfunction in the female has been associated with a decrease in androgen levels, which can be reversed by testosterone treatment, however, bearing the risk of adverse side effects. Nasally administered testosterone could be an effective method for androgenic treatment avoiding the first-pass intestinal and hepatic metabolism and side effects. Here we examined the effects of chronic intranasal administration of testosterone on sexual behavior in female capuchin monkeys (Cebus apella) that lived with male cohorts. During 8 days of baseline 10 females were observed for their sexual and non-sexual behavior without drug. They then received daily intranasal testosterone (0.24 mg per nostril, n=5 per group) or placebo gel for 5 days, followed by 5 days of wash out, followed by 5 days of daily intranasal application, whereby the animals that had received testosterone before, now received placebo and vice versa. Diverse sexual and non-sexual behaviors were scored. Blood samples were collected and analyzed for testosterone, estradiol, dihydrotestosterone and progesterone using EIAs. The results revealed an increase in sexual behavior (eyebrow raising, chest rubbing, courtship behavior, masturbation) in the females during testosterone treatment, which seemed to be prolonged even when testosterone treatment was discontinued. These behavioral results were accompanied by an increase in plasma testosterone levels. This study demonstrates the efficacy of testosterone in enhancing sexual behavior in female capuchin monkeys by means of intranasal application, which may be a useful alternative compared to other forms of administration. PMID- 17280727 TI - Effect of different cyanobacterial biomasses and their fractions with variable microcystin content on embryonal development of carp (Cyprinus carpio L.). AB - While numerous studies focused on the effects of microcystins, the role of other components of complex cyanobacterial water blooms in toxicity is poorly understood. In this study we have evaluated effects of various fractions of cyanobacterial biomass with different composition and microcystin content on embryolarval development of carp (Cyprinus carpio). The following samples (fractions) of four natural water blooms were prepared and tested: complex cyanobacterial biomass, crude aqueous extract of biomass, cellular pellet remaining from aqueous extract, permeate (i.e. microcystin-free fraction prepared during C-18 solid-phase extraction; SPE), and eluate (i.e. fraction prepared by SPE containing mostly microcystins). Complex biomass and the crude aqueous extract (regardless of microcystin content and/or microcystin variants present) in the sample were the most toxic. On the other hand, eluate fractions of all samples containing microcystins in concentrations 8-255 microgL(-1) induced no or only weak toxic effects. Exposures of fish to permeate fractions (with removed microcystins) of two samples dominated by Aphanizomenon sp. and Planktothrix sp. resulted in significant mortality, while other two samples dominated by Microcystis spp. induced minor effects. We have also observed significant inhibition of glutathione S-transferases (GST) at most fractions of the Aphanizomenon sp. and Planktothrix sp. dominated samples. Our data indicate that cyanobacterial water blooms as well complex biomass extracts induce significant embryolarval toxicity in common carp. However, these effects were independent of microcystin content, and the most pronounced effects were observed with the non Microcystis dominated samples. Therefore, a critical examination of microcystin role in overall ecotoxicology of complex cyanobacterial blooms is needed. PMID- 17280728 TI - Molecular cloning and characterization of Ac-MTP-2, an astacin-like metalloprotease released by adult Ancylostoma caninum. AB - Ac-MTP-2 is an astacin-like metalloprotease secreted by adult Ancylostoma caninum hookworms. Ac-mtp-2 cDNA was cloned by immunoscreening a cDNA library with antisera prepared against adult A. caninum excretory/secretory (ES) products. The full-length Ac-mtp-2 contains 850 bp cDNA encoding a 233 amino acid open reading frame (ORF) with 32% amino acid identity to Ce-NSP-4, a pharyngeal cell-derived secreted metalloprotease of the nematode Caenorhabditis elegans. The predicted ORF contained a conserved Met-turn sequence (SXMHY), but only a partial zinc binding signature sequence (GXXXEHXRXER instead of HEXXHXXGXXHEXXRXDR) found in other astacins. However, by both gelatin gel electrophoresis and azocasein digestion, the recombinant Ac-MTP-2 exhibited proteolytic activity that was inhibited by the zinc chelator 1,10-phenanthroline and Ac-TMP, a putative tissue inhibitor of metalloprotease that was previously shown to be a highly abundant component of adult A. caninum ES products. By RT-PCR, Western blot Ac-MTP-2 was found only expressed in adult hookworms and secreted in the adult ES products. Immunolocalization with antisera shows that Ac-MTP-2 is located to the esophageal glands (confirming its role as a secretory protein), as well as to the parasite uterus. It is hypothesized that Ac-MTP-2 functions in the extracorporeal digestion of the intestinal mucosal plug lodged in the buccal capsule of the adult parasite. PMID- 17280729 TI - A dynamic, optimal disease control model for foot-and-mouth disease: I. Model description. AB - A dynamic optimization model was developed and used to evaluate alternative foot and-mouth disease (FMD) control strategies. The model chose daily control strategies of depopulation and vaccination that minimized total regional cost for the entire epidemic duration, given disease dynamics and resource constraints. The disease dynamics and the impacts of control strategies on these dynamics were characterized in a set of difference equations; effects of movement restrictions on the disease dynamics were also considered. The model was applied to a three county region in the Central Valley of California; the epidemic relationships were parameterized and validated using the information obtained from an FMD simulation model developed for the same region. The optimization model enables more efficient searches for desirable control strategies by considering all strategies simultaneously, providing the simulation model with optimization results to direct it in generating detailed predictions of potential FMD outbreaks. PMID- 17280730 TI - A dynamic, optimal disease control model for foot-and-mouth-disease: II. Model results and policy implications. AB - A dynamic optimization model was used to search for optimal strategies to control foot-and-mouth disease (FMD) in the three-county region in the Central Valley of California. The model minimized total regional epidemic cost by choosing the levels of depopulation of diagnosed herds, preemptive depopulation, and vaccination. Impacts of limited carcass disposal capacity and vaccination were also examined, and the shadow value, the implicit value of each capacity, was estimated. The model found that to control FMD in the region, (1) preemptive depopulation was not optimal, (2) vaccination, if allowed, was optimal, reducing total cost by 3-7%, (3) increased vaccination capacity reduced total cost up to US$119 per dose, (4) increased carcass disposal capacity reduced total cost by US$9000-59,400 per head with and without vaccination, respectively, and (5) dairy operations should be given preferential attention in allocating limited control resources. PMID- 17280731 TI - The use of multiplex PCR to detect and differentiate food- and beverage associated microorganisms: a review. AB - Regarding food safety, rapid detection of microbial species is crucial to develop effective preventive and/or adjustment measures. Classical methods for determining the presence of certain species are time-consuming and labor intensive, hence, molecular methods, which offer speed, sensitivity and specificity, have been developed to address this problem. Multiplex PCR (MPCR) is widely applied in the various fields of microbiology for the rapid differentiation of microbial species without compromising accuracy. This paper describes the method and reports on the state-of-the-art application of this technique to the identification of microorganisms vehiculated with foods and beverages. The identification of both pathogens and probiotics and the species important for food fermentation or deterioration will be discussed. Applications of MPCR in combination with other techniques are also reviewed. Potentials, pitfalls, limitations and future prospects are summarised. PMID- 17280732 TI - Lignin deficiency in transgenic flax resulted in plants with improved mechanical properties. AB - Flax (Linum usitatissimum L.) is a very important source of natural fibres used by the textile industry. Flax fibres are called lignocellulosic, because they contain mainly cellulose (about 70%), with hemicellulose, pectin and lignin. Lignin is a three-dimensional polymer with a high molecular weight, and it gives rigidity and mechanical resistance to the fibre and plant. Its presence means the fibres have worse elastic properties than non-lignocellulosic fibres, e.g. cotton fibres, which contain no lignin. The main aim of this study was to produce low lignin flax plants with fibres with modified elastic properties. An improvement in the mechanical properties was expected. The used strategy for CAD down regulation was based on gene silencing RNAi technology. Manipulation of the CAD gene caused changes in enzyme activity, lignin content and in the composition of the cell wall in the transgenic plants. The detected reduction in the lignin level in the CAD-deficient plants resulted in improved mechanical properties. Young's modulus was up to 75% higher in the generated transgenic plants (CAD33) relative to the control plants. A significant increase in the lignin precursor contents and a reduction in the pectin and hemicellulose constituents was also detected. A decrease in pectin and hemicellulose, as well as a lower lignin content, might lead to improved extractability of the fibres. However, the resistance of the transgenic lines to Fusarium oxysporum was over two-fold lower than for the non-transformed plants. Since Fusarium species are used as retting organisms and had been isolated from retted flax, the increased sensitivity of the CAD-deficient plant to F. oxysporum infection might lead to improved flax retting. PMID- 17280733 TI - Molecular epidemiology of bluetongue virus serotype 4 isolated in the Mediterranean Basin between 1979 and 2004. AB - The nucleotide sequences of genome segments 2, 7, 8, 9 and 10, coding for viral proteins (VP) and non-structural proteins (NS)--VP2, VP7, NS2, VP6 and NS3/NS3A, respectively, were determined and compared for 10 strains of bluetongue virus (BTV) serotype 4 isolated in the Mediterranean Basin between 1979 and 2004, and the South African attenuated BTV 4 vaccine strain. The sequence data generated for the BTV 4 strains isolated in Greece in 1979, 1999 and 2000 showed that they had a common origin but were distinct from the lineage of the BTV 4 strains isolated from 2003 onward in the western Mediterranean Basin (Italy, Morocco, Spain and Corsica). The nucleotide and deduced amino acid (aa) sequences of the BTV 4 strains within each lineage were identical to each other, irrespective of the year of isolation or the geographical location. Although the sequence of VP2 from the Turkish and Greek strains were highly similar, there were sufficient differences in the VP6, VP7 and NS2 proteins to suggest that the Turkish BTV 4 belongs to a third lineage. Alignment of the NS3 sequences from the attenuated BTV 4 vaccine strain and the field strains showed 13 aa substitutions, which may, either singularly or together, be responsible for attenuation and hence determining the virulence of the virus. PMID- 17280734 TI - Hepatitis B virus genetic diversity in Latin America. AB - Hepatitis B virus (HBV) infection is still a significant health concern in Latin America, where around 11 million persons are infected. Amerindian populations exhibit the highest prevalences of infection in the region. HBV exhibits a degree of variability intermediate between DNA and RNA viruses. This plasticity leads to the generation of several mutants and genotypic variability. Eight HBV genotypes (A-H) have been described, based on a minimum divergence of 8% of the complete genome sequences. HBV genotype F is the most divergent of the HBV genotypes, is autochthonous to South America and is highly predominant in the Northern region of South America. The recently described HBV genotype H is closely related to genotype F and seems to be restricted to Central and North America. Recombination among different HBV strains seems to be frequent, although it has not been described yet between American genotypes. Inside HBV genotype F, four subgenotypes have been described, which exhibit a geographic pattern of distribution. The clinical and biologic importance of the genotypic diversity of HBV is of major concern at the present moment and has been studied in Asia and Europe. In contrast, it is not known whether infection with the American HBV genotypes F and H is associated with a rapid or slow development of disease. The origin of HBV is still an open question. Depending on the model used for the phylogenetic analysis, an Asian or an American origin of HBV has been proposed. By revisiting the genotypic diversity of HBV, an alternative explanation is that human HBV genotypes might have emerged by several zoonotic introductions, both in the Old and the New World. PMID- 17280735 TI - What are the molecular ties that maintain genomic loops? AB - The formation of genomic loops by proteins bound at sites scattered along a chromosome has a central role in many cellular processes, such as transcription, recombination and replication. Until recently, few such loops had been analyzed in any detail, and there was little agreement about the nature of the molecular ties maintaining these loops. Recent evidence suggests that loops are found in both prokaryotes and eukaryotes, and that the transcription machinery is a molecular tie. In addition, results obtained using site-specific recombination in bacteria and chromosome conformation capture in eukaryotes support the idea that active transcription units are in close contact. These data are consistent with a model for genome organization in which active polymerases cluster into transcription 'factories', which, inevitably, loops the intervening DNA. They are also consistent with the ties functioning as barriers, silencers, enhancers or locus control regions, depending on their positions relative to other genes. PMID- 17280736 TI - Presenilin diversifies its portfolio. AB - Presenilin, the catalytic member of the gamma-secretase proteolytic complex, was discovered through its roles in generating Alzheimer's-disease-associated amyloid beta peptides from the amyloid-beta precursor protein and in releasing the transcriptionally active domain of the receptor Notch. Recent work has revealed many additional cleavage substrates and interacting proteins, suggesting a diversity of roles for presenilin during development and adult life, some of which might contribute to Alzheimer's disease progression. Although many of these functions depend on the proteolytic activity of gamma-secretase, others are independent of its role as a protease. Here, we review recent data on candidate functions for presenilin and its interactors and on their potential significance in disease. PMID- 17280737 TI - Mitochondrial introns: a critical view. AB - Although group I and group II introns were discovered more than 25 years ago, they are still difficult to identify. Modeling their RNA structure also remains particularly challenging for organelle sequences, owing to their great diversity. In fact, accelerated evolution in organelles often results in a reduced RNA structure and a loss of autocatalytic splicing and intron mobility. We set out to identify all mitochondrial group I and II introns in published sequences, and, to this end, we developed and applied a new search approach: RNAweasel. On the basis of the results, we focus here on building a comprehensive picture of mitochondrial group I introns, including a modified (reduced) consensus RNA secondary structure and a concise phylogeny-based subclassification. PMID- 17280738 TI - Induction of monocyte chemoattractant protein-1 release from A549 cells by agonists of protease-activated receptor-1 and -2. AB - Hypersecretion of cytokines and serine proteases has been observed in asthma. However, the influence of proteases and protease-activated receptors (PARs) on monocyte chemoattractant protein-1 (MCP-1) release from airway epithelial cells remains largely unknown. In the present study, A549 cells were challenged with agonists of PARs, and levels of MCP-1 released in the supernatant and mRNA expression were examined by ELISA and real time polymerase chain reaction (PCR), respectively. The results show that thrombin, tryptase, elastase and trypsin induced an up to 6.5-, 1.8-, 1.6-, and 3.1-fold increase in MCP-1 release from A549 cells, respectively, following a 16-h incubation period. The protease induced secretion of MCP-1 can be abolished by specific protease inhibitors. Agonist peptides of PAR-1 and PAR-2 stimulate MCP-1 secretion up to 15- and 12.7 fold, respectively. Real-time PCR showed that MCP-1 mRNA is up-regulated by the serine proteases tested and by agonist peptides of PAR-1 and PAR-2. In conclusion, serine proteases can stimulate MCP-1 release from A549 cells possibly through a PARs-related mechanism, suggesting that they are likely to contribute to MCP-1-related airway inflammatory disorders in man. PMID- 17280739 TI - Pigmented plexiform neurofibroma: Distinction from a large congenital melanocytic nevus. AB - The substantial clinical and histologic overlap between neurotized congenital melanocytic nevi and the subset of plexiform neurofibromas with hyperpigmentation and hypertrichosis of the overlying skin (pigmented neurofibroma) has led to considerable confusion in the literature. A dark-brown, hypertrichotic plaque covered much of the right lower aspect of the trunk of a 1-year-old girl with a diffuse and plexiform neurofibroma in the same area, numerous cafe-au-lait macules, and intertriginous freckling. The latter findings were diagnostic of neurofibromatosis-1, which was further supported by the presence of unidentified bright objects on magnetic resonance imaging of the brain. Histologic examination of the hyperpigmented plaque revealed melanocytic hyperplasia at the dermoepidermal junction and a proliferation of rounded, pigmented melanocytes dispersed individually and in occasional small nests in the papillary dermis and scattered within underlying neurofibromatous tissue. Immunohistochemical staining with A103 (Melan-A/MART-1) and PNL2 confirmed the melanocytic differentiation of the pigmented cells, whereas glial fibrillary acidic protein and Leu-7 were detected only within plexiform areas and slender neuroid spindle cells. This case draws attention to the pigmented neurofibroma as a distinct clinicopathologic entity resulting from proliferation of melanocytes and neurosustentacular cells in the setting of neurofibromatosis-1. PMID- 17280740 TI - Concerted action of antiepileptic and antidepressant agents to depress spinal neurotransmission: Possible use in the therapy of spasticity and chronic pain. AB - Chronic pain states and epilepsies are common therapeutic targets of voltage gated sodium channel blockers. Inhibition of sodium channels results in central muscle relaxant activity as well. Selective serotonin reuptake inhibitors are also applied in the treatment of pain syndromes. Here, we investigate the pharmacodynamic interaction between these two types of drugs on spinal neurotransmission in vitro and in vivo. Furthermore, the ability of serotonin reuptake inhibitors to modulate the anticonvulsant and windup inhibitory actions and motor side effect of the sodium channel blocker lamotrigine was investigated. In the hemisected spinal cord model, we found that serotonin reuptake inhibitors increased the reflex inhibitory action of sodium channel blockers. The interaction was clearly more than additive. The potentiation was prevented by blocking 5-HT(2) receptors and PKC, and mimicked by activation of these targets by selective pharmacological tools, suggesting the involvement of 5-HT(2) receptors and PKC in the modulation of sodium channel function. The increase of sodium current blocking potency of lamotrigine by PKC activation was also demonstrated at cellular level, using the whole-cell patch clamp method. Similar synergism was found in vivo, in spinal reflex, windup, and maximal electroshock seizure models, but not in the rotarod test, which indicate enhanced muscle relaxant, anticonvulsant and analgesic activities with improved side effect profile. Our findings are in agreement with clinical observations suggesting that sodium channel blocking drugs, such as lamotrigine, can be advantageously combined with selective serotonin reuptake inhibitors in some therapeutic fields, and may help to understand the molecular mechanisms underlying the interaction. PMID- 17280741 TI - Use it or lose it? SES mitigates age-related decline in a recency/recognition task. AB - An important goal of aging research is to determine factors leading to individual differences that might compensate for some of the deleterious effects of aging on cognition. To determine whether socio-economic status (SES) plays a role in mitigating age-related decrements in the recollection of contextual details, we categorized older participants into low- and high-SES groups. Event-related potentials (ERPs) and behavioral data were recorded in a picture memory task involving recency and recognition judgments. Young, old-low and old-high SES groups did not differ in recognition performance. However, on recency judgments, old-low subjects performed at chance, whereas old-high subjects did not differ significantly from young adults. Consistent with their preserved recency performance, a long-duration frontal negativity was significantly larger for recency compared to recognition trials in the ERPs of the old-high SES group only. These data suggest that older adults with higher SES levels can use strategies to compensate for the adverse effects of aging in complex source memory tasks by recruiting additional neural resources apparently not required by the young. PMID- 17280743 TI - Mucosal priming with PEI/DNA complex and systemic boosting with recombinant TianTan vaccinia stimulate vigorous mucosal and systemic immune responses. AB - An effective vaccine strategy for HIV-1 will probably requires the induction and maintenance of both humoral and cellular immunity. We tested a new prime-boost approach of intranasal priming with 10 microg DNA plasmid in the PEI/DNA complexes and boosting with 10(7)PFU of replicative recombinant TianTan vaccinia virus (rTTV) expressing HIV-1 Gag in BALB/c mice. Intranasal priming with PEI/DNA complexes elicited strikingly stronger HIV-specific T-cell (p=0.0358) and IgA immune responses at mucosal sites of lung (p=0.0445) and vaginal tract (p=0.0469) than intranasal priming with naked DNA, though both are followed by the same rTTV boosting. Furthermore, an intramuscular boosting with rTTV could profoundly enhance both T-cell and antibody immune responses raised by intranasal priming. These results demonstrate that the combination of intranasal priming with PEI/DNA complexes and systemic boosting with rTTV is a preferable regimen for induction of both T-cell and humoral immune responses. PMID- 17280744 TI - Safety and immunogenicity of the Plasmodium falciparum merozoite surface protein 3 long synthetic peptide (MSP3-LSP) malaria vaccine in healthy, semi-immune adult males in Burkina Faso, West Africa. AB - The merozoite surface protein-3 long synthetic peptide (MSP3-LSP) comprises the amino acid sequence 186-276 of the Plasmodium falciparum protein MSP3. It is currently in development as an erythrocytic stage (blood stage) malaria vaccine candidate. We report here the first data on the safety, reactogenicity and immunogenicity of three doses of MSP3-LSP, adjuvanted with aluminium hydroxide, in healthy male adults living in a malaria endemic area. METHODS: A phase 1b single-blind controlled trial was performed in the village of Balonghin in Burkina Faso. Thirty male volunteers aged 18-40 years were randomised to receive either three doses of 30 microg MSP3-LSP or 0.5 ml of tetanus toxoid vaccine. The second and third vaccine doses were given 28 and 112 days after the first dose. We followed participants for 1 year. RESULTS: There were no serious adverse events in either vaccine group. In both groups participants reported local reactions at the site of injection when compared to an earlier trial in European volunteers. Only one systemic adverse event (tachycardia) was identified which occurred immediately after the first vaccination in one individual receiving MSP3 LSP. No clinically significant biological abnormalities following vaccination were observed. Humoral immune responses (IgG, IgG subclasses, IgM) to MSP3-LSP peptide were similar in the two groups following vaccination. Some cell-mediated immune responses appeared to differ between the two vaccine groups. After the second dose of MSP3-LSP, there appeared to be a marked increase in the lymphocyte proliferation index and IFN-gamma in response to stimulation with MSP3-LSP. CONCLUSION: These data suggest that three doses of 30 microg MSP3-LSP when administered subcutaneously on days 0, 28 and 112 are well-tolerated by adult males previously exposed to natural P. falciparum infection. They also suggest that MSP3-LSP is able to stimulate an enhanced cell-mediated immune response in individuals with some degree of preexisting immunity. PMID- 17280745 TI - Prevention of pertussis: recommendations derived from the second Global Pertussis Initiative roundtable meeting. AB - The Global Pertussis Initiative (GPI) was established in 2001 to assess the global extent of the ongoing problem of pertussis and to evaluate and prioritize pertussis control strategies. Exchange of data, knowledge, and experience, facilitated by discussion and debate, resulted in the formulation, in 2002, of the following recommendation: all countries should consider expanding existing vaccination strategies to include adding pertussis booster doses to pre-school children (4-6 years old), to adolescents, and to those specific adults that have the highest risk of transmitting Bordetella pertussis infection to vulnerable infants. The GPI met again in 2005, where it reinforced its previous recommendation for universal adolescent immunization. Additionally, the GPI recommended implementation of the cocoon strategy (immunization of family members and close contacts of the newborn) in countries where it is economically feasible, and encouraged efforts toward global standardization of pertussis disease clinical definitions and diagnostics. Universal adult vaccination is a logical goal for the ultimate elimination of pertussis disease, but feasibility issues remain obstacles to implementation. PMID- 17280746 TI - Two vaccine toxicity-related genes Agp and Hpx could prove useful for pertussis vaccine safety control. AB - Conventional animal tests such as leukocytosis promoting tests have been used for decades to evaluate toxicity of pertussis vaccine. Here, we examined gene expression in relation to the vaccine toxicity using a DNA microarray. Comparison of conventional animal test data with the DNA microarray-based gene expression data revealed a gene expression pattern highly correlated with leukocytosis in animals. Of 10,490 rat genes analyzed, two genes, alpha1-acid-glycoprotein (Agp) and hemopexin (Hpx), were found up-regulated by the toxin administration in a dose-dependent manner (assayed by a quantitative PCR based on the microarray). Variation of the gene expression was very small amongst the test animals, and the results were highly reproducible. These findings suggest that gene expression analysis of vaccine-treated animals can be used as an accurate and simple method of pertussis vaccine safety assessment. PMID- 17280747 TI - Seroprevalence of rubella among Jordanian women of childbearing age. AB - This study was conducted to assess immunity (seroprevalence) to rubella among Jordanian women of childbearing age. A multistage cluster sampling was used to recruit 1125 women of childbearing age (15-49 year) from the 12 Governorates of Jordan. Anti-rubella antibody titers were measured using enzyme-linked immunoassays. The overall immunity rate to rubella among women in childbearing age was 90.9% (CI: 88.8-92.9). However, the immunity rate was significantly lower in younger women aged 15-19 years (83%) compared to the whole cohort (P99% reductions in fecal rotavirus shedding) but only when co-administered with an effective adjuvant such as LT(R192G). Here, we showed that Biojector needle-free injection of VP6-encoded plasmids also induced protection (85-93%) when they were co-administrated with LT(R192G)-encoded plasmids. A reduction in the amount of VP6 plasmid from 50 to 10 microg reduced protection from 93 to 70%, but the immunized mice remained significantly (P<0.05) protected. Intramuscular needle injection of VP6/LT(R192G)-plasmids also induced significant protection (66%). PMID- 17280755 TI - HLA supertypes and immune responses to measles-mumps-rubella viral vaccine: findings and implications for vaccine design. AB - Although the outcome of the immune response to measles-mumps-rubella (MMR) vaccination depends on multiple factors, elucidation of specific host genetic markers, such as HLA supertypes based on a shared sequence motif in the peptide binding pockets of HLA molecules, is essential. We studied the association between measures of humoral and cellular immune responses and HLA supertypes among 346 children previously immunized with two doses of MMR. We found that HLA supertypes, such as A3, B7, B44, B58, B62, and DR may play a role in modulating immune responses to the measles and mumps components of MMR vaccine. This information may be of significant value in the engineering of potential epitope based vaccines that are recognized by T cells restricted by human HLA supertype alleles. PMID- 17280756 TI - Immunogenicity of a subunit vaccine against Bacillus anthracis. AB - The current approved vaccine against anthrax is based on protective antigen (PA) of Bacillus anthracis, requires six injections over an 18-month period and has a known history of side effects. Therefore, there is significant effort towards developing an improved vaccine against B. anthracis. Here we separately engineered and expressed domain 4 of PA (PAD4) and domain 1 of lethal factor (LFD1) as fusions to lichenase (LicKM), a thermostable enzyme from Clostridium thermocellum, and transiently expressed these fusions in Nicotiana benthamiana. Plant-produced antigens were combined and immunogenicity was evaluated in mice. All animals that received the experimental vaccine developed high antibody titers that were predominantly IgG1 and were able to neutralize the effects of LeTx in vitro. PMID- 17280757 TI - Nucleic acid-based antiviral drugs against seasonal and avian influenza viruses. AB - Influenza viruses are etiological agents of deadly flu that continue to pose global health threats, and have caused global pandemics that killed millions of people worldwide. The availability of neuraminidase inhibitors and attenuated vaccines improves our ability to defend against influenza, but their benefits can be significantly limited by drug-resistance and virus mutations. Nucleic acid based drugs may represent a promising class of antiviral agents that could play a role in the prevention and treatment of influenza. Efficacy studies in animals have shown that ds RNA, such as poly ICLC can provide effective and broad spectrum prophylaxis against lethal challenges against various strains of influenza A virus. Furthermore, similar level of antiviral protection in mice can be provided by using short fragments of oligonucleotides that induce antiviral immunity. Finally, influenza virus expression can also be specifically inhibited or suppressed using antisense oligonucleotides that bind to viral mRNA encoding key viral proteins. The versatility and potency of nucleic acid-based drugs make them potential drug candidates for used in seasonal or pandemic influenza situations. PMID- 17280758 TI - Regional geochemical baselines for Portuguese shelf sediments. AB - Metal concentrations (Al, Cr, Cu, Ni, Pb and Zn) from the DGM-INETI archive data set have been examined for sediments collected during the 1970s from 267 sites on the Portuguese shelf. Due to the differences in the oceanographic and sedimentological settings between western and Algarve coasts, the archive data set is split in two segments. For both shelf segments, regional geochemical baselines (RGB) are defined using aluminium as a reference element. Seabed samples recovered in 2002 from four distinct areas of the Portuguese shelf are superimposed on these models to identify and compare possible metal enrichments relative to the natural distribution. Metal enrichments associated with anthropogenic influences are identified in three samples collected nearby the Tejo River and are characterised by the highest enrichment factors (EF; EF(Pb)<3, EF(Zn)<4). EF values close to 1 suggest a largely natural origin for metal distributions in sediments from the other areas included in the study. PMID- 17280759 TI - Effects of vitamins C and E on steroidogenic enzymes mRNA expression in polychlorinated biphenyl (Aroclor 1254) exposed adult rat Leydig cells. AB - Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell steroidogenic acute regulatory (StAR) protein and steroidogenic enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR protein, cytochrome P(450)scc, 3beta-HSD and 17beta-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while steroidogenic enzymes such as cytochrome P(450)scc, 3beta HSD and 17beta-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254 exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction. PMID- 17280760 TI - Sodium nitroprusside and L-arginine attenuates ferric nitrilotriacetate-induced oxidative renal injury in rats. AB - The role of nitric oxide (NO) in acute renal failure (ARF) is debatable. In the present study, we investigated the effect of acute administration of NO donor, Sodium nitroprusside (SNP), L-Arginine (L-Arg) and NO synthase inhibitor, N(omega)-L-arginine methyl ester (L-NAME) in Fe-NTA induced renal toxicity. Rats were pretreated with SNP (2.5 mg/kg i.p), L-Arg (125 mg/kg, i.p.) and L-NAME (10 mg/kg, i.p.) prior to administration of Fe-NTA (8 mg iron/kg body weight, i.p.) to determine the urea and creatinine levels along with biochemical analysis of oxidative stress. Fe-NTA administration markedly increased the BUN and serum creatinine level which was coupled with a marked lipid peroxidation, decreased levels of reduced glutathione and total nitric oxide levels of rat kidneys coupled with significant morphological alterations. It also resulted in the significant increase in tumor necrosis factor-alpha (TNF-alpha) in serum. Concomitant treatment with SNP and L-Arg significantly reduced the serum creatinine and BUN levels, reduced lipid peroxidation in a significant manner, restored levels of reduced glutathione, increased total nitric oxide levels and restored the normal morphology. Pretreatment with SNP and L-Arg attenuated the levels of TNF-alpha in serum in a significant manner. Prior administration of L NAME reversed the protective effects produced by SNP and L-Arg. Present findings strongly suggest that nitric oxide plays a significant role in the pathophysiology of iron-induced renal failure and administration of NO donors can be valuable in the treatment of ARF. PMID- 17280761 TI - Deoxyribonucleic acid of Chlamydia trachomatis in fresh tissue from the Fallopian tubes of patients with ectopic pregnancy. AB - OBJECTIVES: The role of persistent chlamydial infection of the Fallopian tubes in ectopic pregnancy is still unresolved. Therefore, we examined tissue of the Fallopian tubes from patients with ectopic pregnancy for the presence of Chlamydia trachomatis. In addition, other markers of C. trachomatis infection implicated in the pathogenesis of tubal damage were studied including antibodies to heat shock protein 60 of chlamydial and human origin. STUDY DESIGN: Fresh frozen tubal tissue from 55 patients with ectopic pregnancy in a hospital setting were examined for the presence of C. trachomatis DNA by polymerase chain reaction (PCR) and blood sample were analysed for antibodies to C. trachomatis including heat shock protein 60 (hsp60). RESULTS: Chlamydial DNA was not detected in any of the 55 tubal specimens using a commercial test, Cobas Amplicor, Roche, and an in house real time PCR able to detect a few copies of the organism. Logistic regression showed that chlamydial IgG antibodies were more common in a subgroup of patients with previous PID than in controls (OR=7.84, CI 1.78-34.6). Specific antibodies to hsp60 of chlamydial (OR=7.00, CI 1.50-32.6) but not of human origin (OR=2.13, CI 0.14-31.6) were associated with ectopic pregnancy in this group. CONCLUSIONS: No evidence of persistent infection of C. trachomatis in the fallopian tubes at the time of ectopic pregnancy was found in this study. PMID- 17280763 TI - Determination of granule size distribution in a UASB reactor. AB - Granular sludge is the key factor for an efficient operation of an upflow anaerobic sludge blanket (UASB) reactor. In order to monitor the granularity of anaerobic sludge, the determination of the granule size distribution is of vital importance. For this reason, several techniques have been proposed; however, they are either tedious, imprecise or expensive and hardly applicable in full-scale treatment plants. There was then the need for a simple and low-cost technique. This technique involves the determination of the settling velocities of a sludge sample and of extrapolating the corresponding diameters using a mathematical algorithm. In the proposed algorithm, the granules density was calculated, the flow regime was examined and finally the granule size distribution was obtained. Two very important correlations were suggested by the experimental results. The granule density and diameter were strongly correlated with the VSS/TSS ratio. PMID- 17280762 TI - Estimated nationwide effects of pesticide spray drift on terrestrial habitats in the Netherlands. AB - This study estimated the potential effects of pesticide drift on terrestrial ecosystems outside target areas, for the Dutch situation. A series of field trials was conducted to estimate the effects of drift on different species groups at different distances from a treated plot for different categories of pesticide: herbicides, fungicides and insecticides. Measurements of the pesticide drift deposition resulting from standard agricultural practice were used to model deposition outside the treated area. These data were then combined with national statistics on cropland and pesticide use to assess the ecological effects of pesticide drift for the Netherlands as a whole. Three scenarios were considered: the recent past (1998), the present (2005) and an optimised scenario based on 'best available practice' (2010). In the recent past the impact of herbicide drift on sensitive life stages non-target vascular plants is estimated to have exceeded the 50% effect level on 59% of adjacent linear landscape elements such as ditch banks and hedgerows. For the impact of insecticides and fungicides on non-target insects and fungi this 50% effect figure was 29% and 28% of linear elements, respectively. In the present situation, with (narrow) unsprayed buffer zones and other measures in place, these percentages are down to 41% for herbicides, 21% for insecticides and 14% for fungicides. In the optimised scenario, with a greater buffer width of 2.25m for potatoes (compared to 1.50m in 2005) and 1m for other crops (compared to 0.25 and 0.5m in 2005) and 'best available practice', these percentages can be cut to zero. In natural areas located within farming regions the 10% effect level can be reduced from 31% of such areas (1998) to 0% under conditions of 'best available practice'. PMID- 17280764 TI - Ultrasonic assessment of hepatic blood flow as a marker of mouse hepatocarcinoma. AB - Two-dimensional color-coded pulsed Doppler ultrasonography (US) with a 12-MHz linear transducer was used to follow tumor growth and neoangiogenesis development in 12 transgenic mice developing a whole liver hepatocellular carcinoma (HCC) induced by the expression of SV40-T antigen. In this model, male mice developed HCC at various temporal and histologic stages (hyperplastic, four-eight wk; nodular, 12 wk; diffuse carcinoma, 16-20 wk), whereas female mice remained tumor free. Seven age-matched tumor-free mice were used as controls. Liver volume was calculated from B-mode images of the abdomen. Blood flow waveforms were recorded from the hepatic tumor-feeding artery upstream from the tumor vessels, allowing quantitative blood flow velocity measurements. Measurements were performed every four weeks from four to 20 weeks. As early as the hyperplastic stage (eight weeks), liver volume was increased by 2.7-fold, hepatic artery peak-systolic blood flow velocities (BFV) by 1.5-fold, end-diastolic BFV by 1.6-fold and mean BFV by 2.0-fold compared with control values (p < 0.001). Differences increased until 20 weeks and peak-systolic reached 90 +/- 6, end-diastolic 54 +/- 5 and mean BFV 48 +/- 5 cm s(-1). Successive measurements of BFV were reproducible and intraobserver repeatability coefficient values were <3 cm s(-1). In contrast, mesenteric artery BFV, which did not supply tumor region, did not show any significant difference with respect to control values. Thus, an increase in BFV constitutes a functional evaluation of tumor vascularity. In preclinical studies in small animals, measurements of liver volume and blood flow velocities in hepatic tumor-feeding artery provide a useful, reproducible, noninvasive, easy-to repeat tool to monitor tumor growth and neoangiogenesis in hepatocellular carcinoma in mice. PMID- 17280766 TI - Diagnosis of gallbladder diseases by contrast-enhanced phase-inversion harmonic ultrasonography. AB - We evaluated the usefulness of contrast-enhanced ultrasonography(US) for detecting and differentiating gallbladder lesions. Contrast-enhanced coded phase inversion harmonic US was performed on 90 patients with gallbladder abnormalities. After administering Levovist, we observed the gallbladders in real time. Contrast-enhanced coded phase-inversion harmonic ultrasonography was compared with B-mode US and contrast-enhanced computer tomography (CT) with regard to the sensitivity and specificity in depicting the elevated gallbladder lesions. Furthermore, we assessed how the vascular patterns of the elevated gallbladder lesions depicted by contrast-enhanced US correlated with the diagnosis. Contrast-enhanced US efficiently discriminated true lesions from biliary sludge, unlike B-mode US. Consequently, contrast-enhanced US was more specific (100%) than B-mode US (81%), although their sensitivities were similar (98% and 96%, respectively). Contrast-enhanced US was also more sensitive that contrast-enhanced CT (98% versus 79%), although the two methods were equally sensitive (100% versus 95%). We classified the vascular patterns of the abnormalities depicted by contrast-enhanced US in the 90 cases into types 1 to 4, which represent branch-like, heterogeneous, homogeneous, and avascular patterns, respectively. All type 1 and 2 lesions were over 10 mm in size while most (88%) type 3 lesions were 10 mm or less in size. While the majority of carcinomas (86%) were type 1 or 2, three benign lesions also showed these patterns. Thus, the vascular pattern may simply reflect the size of the lesion and therefore its usefulness in diagnosing gallbladder lesions may be limited. Nevertheless, contrast-enhanced US is clearly superior to the other techniques in discriminating biliary sludge from other lesions. PMID- 17280767 TI - The effects of residual temperature rise on ultrasound heating. PMID- 17280765 TI - Evaluating thin compression paddles for mammographically compatible ultrasound. AB - We are developing a combined digital mammography/3D ultrasound system to improve detection and/or characterization of breast lesions. Ultrasound scanning through a mammographic paddle could significantly reduce signal level, degrade beam focusing and create reverberations. Thus, appropriate paddle choice is essential for accurate sonographic lesion detection and assessment with this system. In this study, we characterized ultrasound image quality through paddles of varying materials (lexan, polyurethane, TPX, mylar) and thicknesses (0.25 to 2.5 mm). Analytical experiments focused on lexan and TPX, which preliminary results demonstrated were most competitive. Spatial and contrast resolution, side-lobe and range lobe levels, contrast and signal strength were compared with no-paddle images. When the beamforming of the system was corrected to account for imaging through the paddle, the TPX 2.5 mm paddle performed the best. Test objects imaged through this paddle demonstrated < or = 15% reduction in spatial resolution, < or = 7.5 dB signal loss, < or = 3 dB contrast loss and range lobe levels > or = 35 dB below signal maximum over 4 cm. TPX paddles <2.5 mm could also be used with this system, depending on imaging goals. In 10 human subjects with cysts, small CNR losses were observed but were determined to be statistically insignificant. Radiologists concluded that 75% of cysts in through-paddle scans were at least as detectable as in their corresponding direct-contact scans. PMID- 17280768 TI - Identification of cardiovascular dilution systems by contrast ultrasound. AB - Indicator dilution techniques permit accurate measurements of important cardiovascular parameters, such as pulmonary blood volume (PBV) and ejection fraction (EF). However, their use is limited by the need for central catheterization. Contrast ultrasonography allows overcoming this problem. PBV and EF can be measured by a dilution system identification algorithm after detection of multiple dilution curves by an ultrasound scanner. In this paper, we present a system identification method that exploits the a priori knowledge on the dilution system and finds the optimum parameters for the parametric model representing the dilution system impulse response. No subsequent model interpolation is needed. Volume measurements show accurate in-vitro results and clinical feasibility, while 50 EF measurements in patients show a 0.88 correlation coefficient with echocardiographic biplane estimates. In conclusion, adding a priori knowledge to the system identification algorithm leads to increased accuracy and robustness of the method for PBV and EF measurements. PMID- 17280769 TI - Noninvasive two-dimensional strain imaging of arteries: validation in phantoms and preliminary experience in carotid arteries in vivo. AB - Cardiac disease and stroke are the major causes of death in the Western World. Atherosclerosis of the carotid artery is the most important predictor of stroke. Elastography is a technique to assess the composition and vulnerability of an atherosclerotic plaque. Contrary to intravascular applications, the ultrasound beam and radial strain are not aligned in noninvasive acquisitions. In this study, 2D displacement and strain images were determined and used to calculate the radial and circumferential strain. Rf-data were acquired using a Philips SONOS 7500 live 3D ultrasound system, equipped with an 11_3L (3 to 11 MHz) linear array transducer and rf-interface. A homogeneous, hollow cylinder phantom [20% gelatin, 1% SiC scatterers (10 microM)] was measured in a water tank at different intraluminal pressures. In addition, measurements in patients (n = 12) were made to evaluate the in vivo applicability of the technique. Longitudinal and cross sectional recordings were made, both in phantoms and patients. Strain along the ultrasound beam (axial strain) was determined using cross-correlation analysis for signal-windows from both the pre- and post-compression data. For lateral strain, new ultrasound lines were generated between the acquired lines using interpolation. A cross-correlation based search algorithm was applied to determine lateral displacement and strain. Longitudinal axial strain images in the phantom showed a decreasing strain from the lumen- vessel wall interface to the outer region that can be described by a 1 over r(2) relationship. The lateral strain image showed no strain in this direction indicating a plane strain situation. In the cross-sectional view, compression of the material in regions at 12 and 6 o'clock was observed, whereas expansion was observed in regions at 3 and 9 o'clock. This pattern is in accordance with theory, but can only be partly corrected for: in the transition regions, zero axial strain was measured. The lateral strain image showed a complementary pattern. In patients, low strain was observed in nonatherosclerotic artery walls. High and low strain regions were found in atherosclerotic plaques. High quality elastograms were generated both in longitudinal and cross-sectional views. In conclusion, 2D noninvasive elastography of atherosclerotic carotid plaques is feasible. Phantom studies revealed elastograms in accordance with theory. Additional in vivo validation is needed to assess the value of this technique for identifying plaque vulnerability and composition. PMID- 17280771 TI - Sensorless reconstruction of unconstrained freehand 3D ultrasound data. AB - Freehand 3D ultrasound can be acquired without a position sensor by finding the separations of pairs of frames using information in the images themselves. Previous work has not considered how to reconstruct entirely freehand data, which can exhibit irregularly spaced frames, intersecting frames, nonmonotonic out-of plane probe motion and significant in-plane motion. This paper presents reconstruction methods that overcome these limitations and are able to robustly reconstruct unconstrained freehand data. The methods are assessed on freehand data sets and compared with reconstructions obtained with a position sensor. PMID- 17280774 TI - A neural model of feature attention in motion perception. AB - We utilize a model of motion perception to link a physiological study of feature attention in cortical motion processing to a psychophysical experiment of motion perception. We explain effects of feature attention by modulatory excitation of neural activity patterns in a framework of biased competition. Our model allows us to qualitatively replicate physiological data concerning attentional modulation and to generate model behavior in a decision experiment that is consistent with psychophysical observations. Furthermore, our investigation makes predictions for future psychophysical experiments. PMID- 17280773 TI - Desmopressin in the treatment of nocturia: a double-blind, placebo-controlled study. AB - OBJECTIVES: To investigate efficacy, safety, and impact on quality of sleep of desmopressin in the treatment of nocturia. METHODS: Adults aged > or =18 yr with nocturia (> or =2 voids/night) received desmopressin tablets (0.1, 0.2, or 0.4 mg) during a 3-wk dose-titration period. Patients should show sufficient response during the dose-titration period (> or =20% reduction in nocturnal diuresis) and a return of nocturnal diuresis to > or =80% of baseline levels during washout. Eligible patients then entered a 3-wk double-blind treatment period and received either desmopressin or placebo. RESULTS: 127 patients were randomised to either desmopressin (n=61) or placebo (n=66). Twenty (33%) desmopressin-treated patients compared with seven (11%) placebo-treated patients showed a clinical response, defined as a > or =50% reduction in the number of nocturnal voids compared with baseline (p=0.0014). Compared with placebo, desmopressin resulted in a significant reduction in the mean number of nocturnal voids (39% reduction with desmopressin vs. 15% with placebo; absolute difference -0.84, p<0.0001) and duration of the first sleep period (prolonged by 108 min with desmopressin vs. 41 min with placebo; p<0.0001). Quality of sleep was also improved with desmopressin versus placebo (statistically significant for one of the two parameters evaluated). Adverse events were mainly mild. CONCLUSIONS: Oral desmopressin tablets provide an effective and well-tolerated treatment for nocturia. Compared with placebo, nocturnal voiding frequency is reduced, duration of the first sleep period is increased, and sleep quality may be improved. PMID- 17280776 TI - Is there a mitochondrial signaling complex facilitating cholesterol import? AB - Cholesterol transport into mitochondria is the rate-determining and hormone sensitive step in steroid biosynthesis. During the last few years two proteins were shown to be critical for this process: the mitochondrial translocator protein, previously known as peripheral-type benzodiazepine receptor, and the steroidogenic acute regulatory protein. In this manuscript we review evidence suggesting that these two proteins functionally interact to facilitate cholesterol transport and may be part of a larger multimeric mitochondrial complex of proteins assembled to facilitate the hormone-induced cholesterol transfer into mitochondria. This complex might include proteins such as the mitochondrial voltage-dependent anion channel, the translocator protein associated protein PAP7 which also functions as an A kinase anchor protein that binds and brings into the complex the regulatory subunit Ialpha of the cAMP dependent protein kinase. PMID- 17280777 TI - Myasthenia gravis and scleroderma: two cases and a review of the literature. AB - Myasthenia gravis is uncommon in patients with scleroderma, and when diagnosed is usually associated with previous use of d-penicillamine. Clinically, both myasthenia and scleroderma may present with fatigue, weakness and bulbar symptoms, so one of diagnoses may be delayed. We report two new cases and review clinical features of 12 other reported cases of co-existing scleroderma and myasthenia gravis, unrelated to previous d-penicillamine therapy. Co-occurrence of myasthenia and scleroderma was reported almost exclusively (13/14) in women with a mean latency of 7.03 years. Most patients (10/11) had seropositive generalized myasthenia, and there were no cases with exclusively ocular symptoms. Three patients with pre-existing myasthenia were safely treated with d penicillamine. Myasthenia and scleroderma occur in the context of an underlying autoimmune diathesis, but their co-occurrence could be underreported as the recognition of either disorder may be delayed by overlapping clinical symptoms. Our findings also suggest that d-penicillamine may be cautiously used in selected patients with pre-existing scleroderma and myasthenia, when potential benefits outweigh the risk of possible myasthenia exacerbation. PMID- 17280775 TI - ESVM: evolutionary support vector machine for automatic feature selection and classification of microarray data. AB - An optimal design of support vector machine (SVM)-based classifiers for prediction aims to optimize the combination of feature selection, parameter setting of SVM, and cross-validation methods. However, SVMs do not offer the mechanism of automatic internal relevant feature detection. The appropriate setting of their control parameters is often treated as another independent problem. This paper proposes an evolutionary approach to designing an SVM-based classifier (named ESVM) by simultaneous optimization of automatic feature selection and parameter tuning using an intelligent genetic algorithm, combined with k-fold cross-validation regarded as an estimator of generalization ability. To illustrate and evaluate the efficiency of ESVM, a typical application to microarray classification using 11 multi-class datasets is adopted. By considering model uncertainty, a frequency-based technique by voting on multiple sets of potentially informative features is used to identify the most effective subset of genes. It is shown that ESVM can obtain a high accuracy of 96.88% with a small number 10.0 of selected genes using 10-fold cross-validation for the 11 datasets averagely. The merits of ESVM are three-fold: (1) automatic feature selection and parameter setting embedded into ESVM can advance prediction abilities, compared to traditional SVMs; (2) ESVM can serve not only as an accurate classifier but also as an adaptive feature extractor; (3) ESVM is developed as an efficient tool so that various SVMs can be used conveniently as the core of ESVM for bioinformatics problems. PMID- 17280778 TI - Particle deposition in indoor environments: analysis of influencing factors. AB - In this paper, several factors influencing particle deposition in indoor environments are analyzed with an analytical model and a three-dimensional drift flux model combined with the particle deposition boundary conditions for wall surfaces. The influences of flow conditions near the wall surfaces, surface roughness and particle concentration distribution on particle deposition indoors are studied. By modeling particle deposition onto surfaces with the analytical model, it is found that larger friction velocity near the wall surfaces and rougher surface may lead to larger particle deposition velocity when the particle size is small, but when particle size is large enough (the range is up to the actual friction velocity and in this study it is about 1-5 microm), the influence of the friction velocity and roughness could be neglected. Furthermore, the three dimensional numerical simulations indicate that particle concentration distribution may be very different even for the same particle source and air change rate, which cause a different deposited particle flux. As the particle concentration distribution may not be uniform in most cases, especially for the ventilated rooms, it is important to incorporate particle concentration distribution when analyzing particle deposition in indoor environments. Some suggestions or rules for particle deposition controlling are also presented based on the analysis. PMID- 17280779 TI - Recovery of nitrotoluenes from wastewater by solvent extraction enhanced with salting-out effect. AB - Toluene extraction enhanced by salting-out effect was employed to recover dinitrotoluene isomers and 2,4,6-trinitrotoluene (2,4,6-TNT) from wastewater of toluene nitration processes (e.g. dinitration or trinitration). The batchwise experiments were conducted to elucidate the influence of various operating variables on the extracting performance, including concentrations and species of inorganic salts, such as NaCl, KCl, Na(2)SO(4), K(2)SO(4) and MgSO4, acidity of wastewater, volume ratios of solvent versus wastewater and extraction stages in existence of inorganic salts. It was found that recovery of total organic compounds (TOC) was significantly elevated with increasing concentrations of salts, whose promoting effects were in the following order: NaCl>Na(2)SO(4)>K(2)SO(4)>MgSO4>KCl on the weight basis of wastewater. Besides, high volume ratio of toluene/wastewater (ca. 2.0) was more suitable for recovery of TOC from wastewater with or without addition of NaCl, of which extractable priority was as follows: 2,6-DNT>2,4-DNT>2,4,6-TNT. It is remarkable that TOC in wastewater would be almost completely recovered by sequential four stages toluene extraction, promoted continuously by salting-out effect. PMID- 17280780 TI - Absence seizures are reduced by the enhancement of GABA-ergic inhibition in the hippocampus in WAG/Rij rats. AB - Classical theories on absence epilepsy suggest that spike-wave discharge (SWDs) represent thalamo-cortical oscillations, where an abnormally excitable cortex interacts with thalamus and brain stem reticular formation. The limbic system is generally not included in any theory about the pathogenesis of absence seizures. However, some data demonstrated that the alterations in the limbic system attribute to the expression of absence epileptic phenotype in genetic models of absence epilepsy. The present study investigated whether local intrahippocampal administration of progesterone (a GABA(A)-mimetic) and tiagabine (an inhibitor of GABA (re)uptake) might affect the occurrence of SWDs. Male WAG/Rij rats were implanted with permanent electroencephalograph (EEG) electrodes and bilateral cannulas in the CA1-CA3 region of the dorsal hippocampus. Control rats had bilateral cannulas in the cortical area above the hippocampus. Rats received intracerebral injections of progesterone (5mg/ml), 45% beta-cyclodextrin (CD), saline, or tiagabine (2mg/ml). EEG recordings were made before and after injection. Progesterone, CD, and tiagabine administration to the hippocampus reduced SWDs for 60min following administration without behavioral or electroencephalographic side-effects. Both progesterone administration into the cortex and saline injection into the hippocampus yielded no changes in the occurrence of SWDs. These data suggest that activation of GABA-ergic transmission in the hippocampus has an inhibitory effect on cortico-thalamo-cortical circuits underlying the generation of SWDs and might be critically involved in the regulation of absence seizures. PMID- 17280781 TI - Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate. AB - The effect of inhibition of glial metabolism by infusion of fluorocitrate (FC, 1 nmol/microl, 2 microl) into the right striatum of the rat brain on the glucose metabolism was studied. Significant increases in [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake (45 min) in the right cerebral cortex and striatum were observed 4h after the infusion of FC, both as determined by the tissue dissection method and autoradiography. No significant increase in the initial uptake of [(18)F]FDG (1 min) was seen in the striatum. Pretreatment with dizocilpine (MK 801), an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced [(18)F]FDG uptake in not only FC infused hemisphere but also in the contralateral hemisphere (saline-infused side). The radioactivity concentrations in plasma at 1, 5 and 45 min after the [(18)F]FDG injection were not altered by MK-801. This effect of MK 801 on glucose metabolism observed in the rat brain infused with FC was different from previous reports which indicated an increase in glucose metabolism in some areas of normal rat brain. In addition, the enhancement of glucose metabolism in the striatum induced by FC was almost completely abolished by pretreatment with MK-801. In the cerebral cortex, the relative ratio of radioactivity concentration in the right hemisphere to that in the left hemisphere still remained 1.37 (tissue dissection method) or 1.55 (autoradiography), which indicated that MK-801 partially blocked the effect of FC of enhancing glucose metabolism in this region. These results indicate an important role of NMDA-mediated signal transmission on the increase of glucose utilization induced by inhibition of glial metabolism. PMID- 17280783 TI - A functional polymorphism in the parkin gene promoter affects the age of onset of Parkinson's disease. AB - Mutations in the parkin gene are the major cause of autosomal recessive early onset forms of Parkinson's disease (PD). As reduced parkin expression might also affect the clinical course of idiopathic PD we investigated the effect of a low expressing allele in the parkin promoter region on the age at disease onset (AAO). Patients with PD (n=175) fulfilling standard diagnostic criteria were recruited by experienced neurologists at two movement disorders clinics in Sydney and Brisbane, Australia. DNA was extracted from whole blood and the -258 T/G polymorphism genotyped using PCR/RFLP. AAO effects were analysed using univariate ANOVA, binomial logistic regression modelling and Kaplan-Meier survival analysis. Subjects with the GG genotype (n=10, mean AAO=46.2+/-11.5 (S.D.) years) had a significantly lower mean AAO compared to the common TT genotype (n=104, mean AAO=56.1+/-12.7, p=0.02). There was no difference in mean AAO between the TT and TG individuals (n=61, mean AAO=55.3+/-11.6). Stratifying the sample by median AAO (55 years) revealed that the GG genotype was over-represented in the early-onset group (n=9, OR=18.6, 95% CI=1.41-245.3, p=0.03). We speculate that reduced expression of normal parkin protein may result in an early manifestation of PD symptoms. PMID- 17280782 TI - Edaravone inhibits lipid peroxidation in neonatal hypoxic-ischemic rats: an in vivo microdialysis study. AB - The occurrence of hypoxia-ischemia (HI) during early fetal or neonatal stages of an individual leads to the damaging of immature neurons resulting in behavioral and psychological dysfunctions. Free radical-mediated lipid peroxidation is the main cause of neurotoxicity including neonatal brain damage. Edaravone (3-methyl 1-phenyl-2-pyrazolin-5-one) is a novel anti-oxidant agent and the drug of choice in the treatment of acute ischemic brain disorders in adult patient. The purpose of this study is to determine the direct effects of edaravone in inhibiting the lipid peroxidation production in the neonatal rat brains during hypoxic-ischemic insult by electron paramagnetic resonance (EPR) spectoroscopy and in vivo brain microdialysis. Seven-day-old Wistar rats were subjected to left common carotid artery ligation and a probe was inserted in the rat hippocampus. Edaravone (5, 50, or 100 microM) or saline was perfused with a spin trap agent (alpha-(4 pyridyl-N-oxide)-N-tert-butylnitrone; POBN) before, during and after hypoxia (1h of 8% O2 exposure) and then analyzed by EPR. Edaravone (100 microM) did not show any EPR evidence of POBN adduct formation during and after hypoxic-ischemic insult. However, the EPR signal increased, but not significantly during the hypoxic period in the hypoxic and edaravone 50 microM-treated groups compared to control. Edaravone at 5 microM significantly increased the EPR signals compared to control. This study shows that edaravone directly and dose-dependently inhibited the formation of lipid free radicals produced during hypoxic-ischemic insult in the neonatal rat brain. These results suggest that edaravone is able to attenuate neuronal damage in the rat neonatal brain by inhibiting the formation of lipid radicals. PMID- 17280784 TI - Effects of plantar flexor muscle fatigue induced by electromyostimulation on postural coordination. AB - The aim of the present study was to investigate the influence of a modification of an intrinsic capacity (plantar flexor strength) on the implementation of in phase and anti-phase mode of coordination. Analysis of hip and ankle relative phases during fore-aft tracking task was done before and after an electromyostimulation fatigue protocol on the soleus muscles. Results showed participants used exclusively in-phase and anti-phase modes of coordination, with a sudden switch from one to the other with target frequency increase. Regarding tracking tasks, fatigue induces a decrease of performance for lower frequencies, and a significant decrease of switch frequency (-0.08 Hz) for each subject. In conclusion, changes in mode of coordination implementation suggest that the in phase mode implementation is highly linked to the strength production capacity at the ankle joint. PMID- 17280785 TI - Identification of early disease progression in an ALS rat model. AB - Transgenic rat models of amyotrophic lateral sclerosis (ALS) have recently been developed. Most assays of ALS-symptoms in these models monitor disease onset accurately, but do not identify individuals that will develop these symptoms before the motor deficits become apparent. Peak bodyweight has recently been shown to indicate affected individuals before motor deficits become apparent. However, it must be determined retrospectively due to weight fluctuation. Here, we report that exploratory activities detected by a photobeam activity system (PAS) and wire mesh ascending test can be used to detect slight motor deficits in the early phase of ALS. Thus, these tests may be used in addition to peak bodyweight to monitor early disease progression and to assay efficacy of new therapeutic interventions. PMID- 17280787 TI - The efficacy of frequency-specific acupuncture stimulation on extracellular dopamine concentration in striatum--a rat model study. AB - Acupuncture is a practice that has existed in Chinese society for thousands of years. Today, it is gaining greater acceptance and integration into medical practices of the western world. Its mechanism, however, remains elusive. Our study shows that only specific stimulation frequencies at specific acupoints will induce dopamine release in the corpus striatum, as demonstrated by in vivo microdialysis performed on Sprague-Dawley rats. In the first trial, electroacupuncture (EA) stimulation at 15 Hz and 15 mA was conducted at six different points on the upper limbs of the experimental rats. These points mimic acupoints along six different meridians in the human body. Only Point 2 (corresponding to Pericardium 7) induced a response. In the second trial, EA stimulation at varying frequencies of 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 Hz, and 15 mA were conducted through Point 2. Stimulation at 6 and 15 Hz induced an immediate response; 21 Hz induced a response only after the ceasing of stimulation. All other frequencies failed to induce a response. The data point to the importance of frequency-specific stimulation at specific acupoints for the release of neurotransmitters in the brain. We speculate that each meridian entails a stimulus of a specific frequency and intensity, which induces the release of its associated neurotransmitters or cytokines. This is a concept with far-reaching clinical implications for acupuncture therapy, including the treatment of dopamine-related disorders. PMID- 17280786 TI - Tryptophan-induced central fatigue in exercising rats is related to serotonin content in preoptic area. AB - To assess the effects of increased hypothalamic tryptophan (TRP) availability on 5-HT content in preoptic area on thermoregulation and work production during exercise on treadmill, 20.3 microM of L-TRP (n=7) or 0.15M NaCl (n=6) was injected into the lateral cerebral ventricle of male Wistar rats immediately before the animals started running (18 m min(-1) 5% inclination). Exercise time to fatigue (min), and workload (kgm) were analysed. Core temperature was measured by telemetry. At fatigue, brains were quickly removed and preoptic area (POA), hypothalamus (HP), frontal cortex (FC), hippocampi (HC) were rapidly dissected and frozen immediately in dry ice. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured by HPLC. TRP-exercised rats showed the highest content of 5-HT in the POA and the lowest in the hippocampi compared to the rested and SAL-exercised rats. An inverse relationship between TF and a direct correlation with body temperature changes and POA-5HT levels were observed. A correlation between HC 5-HT content and TF was also found. However, there was no correlation between HC 5-HT content and changes in Tb at fatigue. Finally, our results bring further evidences that increased 5-HT content in POA is involved with an increase in heat production during exercise. In addition, the direct correlation of 5-HT level in hippocampi and TF of TRP-exercised rats suggests that this brain area is also related to motor activity control during exercise. In conclusion, our data indicated that tryptophan-induced central fatigue in exercising rats is related to serotonin content in preoptic area. PMID- 17280788 TI - Pediculosis in Macaca sylvanus of Gibraltar. AB - Pedicinus spp. parasitize several species of nonhuman primates. This is the first published report confirming the presence of Pedicinus albidus (Rudow) infestation in the free-ranging macaques (Macaca sylvanus) of Gibraltar. The diagnosis of pediculosis was based upon finding adult lice on host animals. PMID- 17280789 TI - Non-arteritic anterior ischemic optic neuropathy, PDE-5 inhibitors, and amiodarone: may there be a sex hormone effect for the eye? PMID- 17280791 TI - The theory of cycling antibiotic resistance. PMID- 17280790 TI - High prevalence rate of pituitary incidentaloma: is it associated with the age related decline of the sex hormones levels? AB - Incidental pituitary adenoma is the common finding during brain imaging. According to multistep model of pituitary tumourigenesis genetic alterations provide the initiating event that transforms cells while hormones play a role in promoting cell proliferation. Development of pituitary adenoma in a case of excessive hypophysiotrophic hormones production or reduced feedback suppression by target gland hormones emphasizes the importance of hormonal stimulation in pituitary tumourigenesis. Pituitary hyperplasia has been reported in pregnancy, hypothyroidism and conditions such as CRH or GHRH hypersecretion. Moreover, recent study reported one case of gonadotroph macroadenoma and two cases of gonadotroph cells hyperplasia in patients with Klinefelter syndrome probably due to protracted stimulation of gonadotroph cells because of lack of androgen feedback. Significant changes of the hypothalamic-pituitary-gonadal axis occurred with aging. In females, after menopause, estradiol level decreases by 35-fold and estrone level by 20-fold that results in increased gonadotropins levels. Similarly, FSH, but not LH, level is increased with advancing age in men, too, although the age-related difference in the level is less in comparison with women. Regarding these data, we hypothesised that high prevalence rate of pituitary incidentaloma in the elderly is associated with age-related decline in sex hormones levels and subsequent lack of feedback suppression leading to permanent gonadotrophs stimulation which is the crucial step in the pituitary tumour development. According to previously mentioned multistep model of pituitary tumourigenesis, incidentaloma will develop only in persons with already present intrinsic pituitary cell defects. However, further studies have to answer the questions of whether the incidence of pituitary tumours is more frequent in elderly, whether women with late onset menopause or those taking long-term hormone replacement therapy have lower rate of pituitary incidentaloma, and finally, is there any correlation between pituitary tumours incidence and serum concentrations of LH, FSH, bioavailable testosterone or estradiol. PMID- 17280792 TI - Cell-permeable hypoxia-inducible factor-1 (HIF-1) antagonists function as tumor radiosensitizers. AB - Hypoxia is a common phenomenon in human solid tumors and has been considered as an important, independent negative prognostic factor for response to treatment and survival of tumor patients. Hypoxia-inducible factor-1 (HIF-1) is the central transcription factor which is activated by hypoxia and modulates the expression of many genes involved in cell metabolism, proliferation, apoptosis, angiogenesis. Recently, it has been reported that HIF-1 contributes to tumor radioresistance by upregulating survivin expression under hypoxic conditions. Moreover, in hypoxic tumor cells, HIF-1 dependent signal transduction pathway is activated and could be further enhanced by radiation, thereby providing survival signals to adjacent vascular endothelial cells by upregulation of VEGF and bFGF and resulting in tumor radioresistance through vascular radioprotection. Recent research revealed that the stability of HIF-1alpha, one of the two subunits of HIF-1, determines the whole HIF-1 activity and the C-terminal transactivation domain of HIF-1alpha could reduce HIF-1 activity when overexpressed in tumor cells by disruption of the assembly of HIF-1 transcription complex. Therefore, we postulate that fusion with protein transduction domains would overcome the inability of C-terminal transactivation domain of HIF-1alpha to cross cellular membrane. Thus the recombinant fusion proteins could serve as cell-permeable HIF 1 antagonists, function as both inhibitors of tumor angiogenesis and tumor radiosensitizers, and would be widely used in clinical settings to improve tumor response to radiotherapy. PMID- 17280793 TI - Amniotic membrane: a potential candidate for periodontal guided tissue regeneration? PMID- 17280794 TI - Inspiratory transductance: a potential new measure of the relationship between inspiratory force and the resistance to pulmonary airflow. AB - Most existing lung function tests require a substantial degree of interactive co operation between patient and clinician. This reduces the clinical usefulness of such tests in patients with cognitive impairment (mainly elderly people), a reduced level of consciousness (for example in patients with a head injury or a severe metabolic disturbance) and children too young to perform the tests. There is a need for measures of airways status that are easier to apply. If the airflow is briefly occluded during inspiration the pressure fall in the airway is proportional to the force of contraction of inspiratory muscles and, because it occurs before flow begins, it is not mechanically altered by airflow resistance. The maximum rate of pressure fall is referred to as dP/dt(max) with the units kPas(-1). After the brief occlusion, the air column accelerates at a rate that is dependent on both dP/dt(max) and the resistance to airflow. The maximum rate of change of airflow is referred to as dV/dt(max), with the units Ls(-1)s(-1). This paper posits an hypothesis that the ratio dV/dt(max)/dP/dt(max) provides an index with the units Ls(-1)kPa(-1) that is a measure of the transformation of inspiratory effort into airflow, and can be referred to as inspiratory transductance. This index is predicted to rise when airflow resistance falls, such as would occur when an attack of asthma responds to bronchodilator drugs. The index is expected to continue to retain directional integrity even when inspiratory muscles become fatigued. Measuring the index would require little co operation from a conscious patient and none from an unconscious patient. PMID- 17280795 TI - Treatment of rheumatoid arthritis and other related conditions by provoking a mild infection to be controlled by the immune system itself. AB - When rheumatoid arthritis presents, the immune system overcompensates and acts attacking the joints and the body in general, the same thing occurs with other autoimmune diseases; the immunological mechanisms that manifest in these diseases have been identified, but there is still no explanation as to why this occurs. This article will present a hypothesis that is based on provoking a mild infection in patients with rheumatoid arthritis, and other related autoimmune diseases, an infection that does not result in serious consequences to the health of the patients, but does generate an immunological response, in this manner, the immune system itself, which is overcompensating, will fight the provoked infection instead of causing damage to the body itself. PMID- 17280796 TI - On a possible early identification procedure for babies at high risk for autistic spectrum disorder. AB - A hypothesis for a method that may make possible the early identification of neonates at high risk for later development of autistic spectrum disorder (ASD) is set forth. The method is a test of the assertion that unusually high testosterone concentrations in amniotic fluid (TECAFs) are predictive of later ASD diagnoses. The statistical distribution of TECAFS, obtained in the 14-20th week of pregnancy, is used to determine the critical TECAF value above which the highest 2% lie and thus identify the babies at high risk for later ASD syndromes. From presently available data a single numerical value cannot be obtained. However, a critical value calculated from the mean TECAF value of a group of gender identified amniotic fluid samples, which are all assayed by the same technique, and multiples of the standard deviation (SD) of the TECAFs of that group, leads to an estimate of the critical TECAF value. We estimate that this critical value is equal to the mean plus 2.6 times the standard deviation, (m+2.6 SD), of the set of measurements. A rough calculation of the number of neonates that would be needed for a test of this method is discussed. PMID- 17280797 TI - Tongue contractions during speech may have led to the development of the bony geometry of the chin following the evolution of human language: a mechanobiological hypothesis for the development of the human chin. AB - One of the most fundamental yet unanswered questions of human evolution is that of the development of the chin. Whereas it is known that the chin, or mentum osseum, is an unique anatomical feature of modern humans that emerged during the Middle and Late Pleistocene, its origin and biomechanical significance are the subjects of intense controversy. Theories range from the suggestion that the chin evolved as a result of progressive reduction of the dental arch, which left it as a protrusion, to the hypothesis that it provided resistance to mandibular bending during mastication. Until now however, no accepted functional explanation of the human chin has emerged. Here, we develop the hypothesis that the actions of the tongue and non-masticatory orofacial muscles may have played a significant role on the development of the human chin. We report numerical simulations of the forces and resultant stresses developed in hypothetical chinned and non-chinned mandibles. Using empirical data and estimates of the forces generated by the human tongue during speech, our hypothesis suggests that the chin might in fact have developed as a result of the actions of the tongue and perioral muscles, rather than as a buttress to withstand masticatory induced stress. This provides a new perspective on the generation of the chin and importantly, suggests that its appearance may be causally related to the development of the human language. PMID- 17280798 TI - Fibrin/platelet plug counteracts cutaneous wound contraction: the hypothesis of "skipping stone". AB - Cutaneous wound contraction and epithelialization act collaboratively to minimize the exposed wound surface. However excessive wound contraction is undesirable due to the resultant disfigurement and scarring. Fibrin clot has greater stiffness than surrounding tissue and mechanical strain further enhances its stiffness. On the contrary, skin exhibits diminished stiffness when affected by high strain rates. Therefore during early stages of wound healing, the contractile wound border is confronted by fibrin clot forming a high strain region in the interface of contractile tissue and fibrin clot--which is evidenced by computer simulation. Due to the stress relaxation property of skin, the contractile strain is partly neutralized. Meanwhile, gradually the stiffness of fibrin clot decreases which is followed by another cycle of wound contraction. This cyclic pattern of contraction resembles the movement of a stone over water or "skipping stone". The stone bounces repeatedly when thrown across the surface of water with reduction of jumping altitude with each bounce till the stone stops completely. This hypothesis is further supported by the observed initial delay in wound contraction and the chronological correlation of enhanced wound contraction with loss of superficial eschar and substitution of fibrin clot with granulation tissue. Also there is evidence that fibrin inhibits fibroblast-mediated contraction of collagen. Furthermore, modest increase in wound contraction rate in fibrinogen deficient mice and fibrin-mediated diminished wound contraction are agreement with the proposed hypothesis. PMID- 17280799 TI - Cornering HIV: taking advantage of interactions between selective pressures. AB - Adaptive immune responses, cellular restrictive factors and antiretroviral drugs, target multiple regions in the Human Immunodeficiency Virus (HIV) proteome, imposing diverse pressures to viral adaptation. However, the virus is remarkably able to escape from these pressures as mutations are selected. In many cases these mutants have diminished viral fitness. We propose that the concerted action of strategically placed agents and pressures in a host can limit HIV variation capacity while inhibiting its replication. These mechanisms would corner HIV by selecting conflicting adaptive mutations, each having a disadvantage in face of another selective pressure. This would keep the virus unable to efficiently escape the suppressive effects of selective pressures. Cornering between antiretroviral drugs and cytotoxic T lymphocytes may explain recent observations, and can be predicted and used in viral control strategies. This idea can be extended to numerous other identified sites in the viral genome that confer selective pressures. We describe these other sites and how they could be induced to interact in prophylactic or therapeutic cornering strategies, as well as their experimental verifications. Cornering would control HIV infection better than current strategies, focused on few, albeit important, sites in the HIV genome. PMID- 17280800 TI - Religious, economic and pharmacodynamic factors that hinder the prevention of essential hypertension. PMID- 17280801 TI - Adolescent alcohol use and adult alcohol disorders: a two-part random-effects model with diagnostic outcomes. AB - Alcohol use is often analyzed by treating the behavior as a single dimension, such as focusing on frequency of use. Based on data from a longitudinal study, this report considers two distinct aspects of semi-continuous alcohol use data. A two-part random-effects model was used to evaluate change in the log-odds and frequency of use from about age 13 to about age 18 years. Change features were then related to the log-odds of later alcohol disorders. Results suggested differences in the two aspects of use over time and their relationships with later disorders. Most important for the purposes of this study, different methods of analyzing antecedents and consequences of alcohol use trajectories were shown to generate both similar and disparate findings. PMID- 17280802 TI - Higher syringe coverage is associated with lower odds of HIV risk and does not increase unsafe syringe disposal among syringe exchange program clients. AB - OBJECTIVE: To determine if adequate syringe coverage --"one shot for one syringe" -among syringe exchange program (SEP) clients is associated with injection related HIV risk behaviors and syringe disposal. DESIGN: HIV risk assessments with 1577 injection drug users (IDUs) recruited from 24 SEPs in California between 2001 and 2003. Individual syringe coverage was calculated as a proportion of syringes retained from SEP visits to total number of injections in the last 30 days. RESULTS: Participants were divided into four groups based on syringe coverage: <50%, 50-99%, 100-149%, and 150% or more. In multivariate logistic regression, SEP clients with less than 50% syringe coverage had significantly higher odds of reporting receptive syringe sharing in the last 30 days (adjusted odds ratio [AOR]=2.3; 95% confidence interval [CI]=1.4, 3.6) and those with 150% or more coverage had lower odds of reporting receptive syringe sharing (AOR=0.5; 95%CI=0.3, 0.8) as compared to SEP clients with adequate syringe coverage of 100 149%. Similar associations were observed for other main outcomes of distributive syringe sharing and syringe re-use. No differences in safe syringe disposal were observed by syringe coverage. CONCLUSIONS: Individual syringe coverage is strongly associated with safer injection behaviors without impacting syringe disposal among SEP clients. Syringe coverage is a useful measure for determining if IDUs are obtaining sufficient syringes to lower HIV risk. PMID- 17280804 TI - Evaluation of the effects of the marine toxin okadaic acid by using FETAX assay. AB - The Frog Embryo Teratogenesis Assay Xenopus (FETAX), is a screening assay using embryos at gastrula stage of the anuran Xenopus laevis to identify substances that may pose a developmental hazard in humans. The FETAX assay evaluates three parameters, i.e. mortality, delayed growth and embryo malformation. In the present investigation, the FETAX protocol was applied to the marine toxin okadaic acid (OA) and the experiments show that OA affects the above parameters in a dose correlated manner. The morpho-functional modifications induced in embryo organs by OA were also studied. The nervous system, tail skeletal musculature, intestine and kidney appeared particularly damaged, with the former being the most sensitive. On the whole, various advantages emerge from using the FETAX assay: different parameters can be tested simultaneously, the indication of the presence of a potentially dangerous substance is rapid and the assay is a valid alternative to mammalian systems. PMID- 17280803 TI - Overdose after detoxification: a prospective study. AB - OBJECTIVE: The aim of this study was to determine predictors of non-fatal overdose (OD) among a cohort of 470 adults after detoxification from heroin, cocaine or alcohol. METHODS: We examined factors associated with time to OD during 2 years after discharge from an urban detoxification unit in Boston, MA, USA using multivariable regression analyses. Separate analyses were performed for both the total sample and a subgroup with problem opioid use. RESULTS: Lifetime prevalence for any OD was 30.9% (145/470) in the total sample and 42.3% (85/201) in patients with opioid problems. During the 2-year follow-up, OD was estimated to occur in 16.9% of the total sample and 26.7% of the opioid problem subgroup, with new-onset (incidence) OD estimated at 5.7% and 11.0%, respectively. Factors associated with an increased hazard of OD in both samples included white race, more depressive symptoms, and prior OD regardless of intent. Prior suicidal ideation or attempt was not associated with future OD. CONCLUSIONS: Findings underscore both the high prevalence of non-fatal OD among detoxification patients especially opioid users, and the potency of prior OD as a risk factor for future OD. Depressive symptoms, a modifiable risk factor, may represent a potential intervention target to prevent OD, including some "unintentional" ODs. PMID- 17280805 TI - Geldanamycin augments nitric oxide production and promotes capacitation in boar spermatozoa. AB - Sperm capacitation and the acrosome reaction are fundamentally important to fertilization. Nitric oxide (NO) has been shown to have various functions in male reproduction. This work investigates whether boar sperm can generate NO, as well as the effects of NO and geldanamycin (GA), a heat-shock protein 90 (HSP90) specific inhibitor, on the capacitation of boar spermatozoa. Observations showed that porcine sperm produced low levels of NO under non-capacitating conditions. However, the NO concentration almost doubled under capacitating conditions (P<0.001). Treatment with NG-nitro-L-arginine methyl ester (L-NAME) reduced the production of NO by 30-40% in capacitating sperm (P<0.05). GA treatment increased it by 23-75% in a dose-dependent manner (P<0.05). L-NAME treatment reduced the percentage of sperm undergoing the acrosome reaction, whereas sodium nitroprusside, an NO-releasing compound, and GA treatment increased the percentage of sperm undergoing the acrosome reaction (P<0.05). GA treatment promoted the production of NO and the acrosome reaction. The increase in NO production by GA treatment was similar to that caused by the calcium ionophore, A23187, suggesting that the GA-induced acrosome reaction may be triggered by an increase of the intracellular calcium concentration. The signaling pathway involved in GA-mediated NO production and its biological function in fertilizing boar spermatozoa will be elucidated in further studies. PMID- 17280806 TI - Construction and characterization of phage display library: recognition of mouse serologically detected male (SDM) antigen. AB - Improvement of animal embryo sexing depends upon high-titer serologically detected male (SDM) antibody fragments. SDM sera collected from isogenic C57BL/7 female mice after inoculation with male spleen cells were characterized and used for construction of a recombinant Fab antibody library against SDM antigen, and used for analysis of the binding capacity and specificity to SDM antigen. The heavy-chain Fd and full-length light-chain kappa were amplified by RT-PCR from a mouse (#6) that'ed high-titer antiserum. The amplified product was inserted into the pComb3 vector followed by co-infections with the help phage VCSM 13 for construction of the phage library, which gave 1.5x10(7) colonies with the titer of 3.2x10(11) pfu/ml by a recombination rate of 80%. Sequence analysis of the PCR products of plasmid DNA of E5 clones showed that V(H) and V(kappa) had common characteristics shared by other known variable region of antibodies. The Fab antibody libraries against SDM antigen were enriched by three cycles of affinity enrichment with male spleen cells, and two cycles of non-specific absorption with female spleen cells. The ELISA results showed that 9 of 15 clones had binding capacity to the SDM antigen. This is the first report on a phage display library of SDM antigen. The mouse Fab antibody library could be used for identifying SDM antigen, and for the development of sex determination of early embryos in mammals. PMID- 17280807 TI - Duration of fertility and osteoporosis. PMID- 17280808 TI - Comparison of oral bioavailability of genistein and genistin in rats. AB - Genistein (GT) is an isoflavone from Leguminosae and has received much attention as a phytoestrogen. Genistin is a glycoside form of GT (genistein-7-O-beta-D glucopyranoside, GT-glu) is mainly found in soy-derived foods. In this study, we examined the pharmacokinetic properties and bioavailability of GT in rats and compared with those of GT-glu. In order to characterize and compare the pharmacokinetics of GT and GT-glu, these compounds were administered intravenously and orally. The plasma concentration of GT was determined by HPLC after enzymatic hydrolysis. After oral administration of GT with various doses (4, 20, 40 mg/kg), the bioavailability of GT was 38.58, 24.34 and 30.75%, respectively. The T(max), C(max) and AUC(0-infinity) of GT after oral administration of GT (40 mg/kg), were 2h, 4876.19 ng/ml, 31,269.66 ng h/ml, respectively. When smaller amount of GT was administered, the faster T(max) was observed. Oral administration of GT-glu resulted in longer T(max), lower C(max), and greater bioavailability than that of GT. The pharmacokinetic parameters of GT following oral administration of GT-glu (64 mg/kg as GT-glu, 40 mg/kg as GT) were obtained as follows: 8h (T(max)), 3763.96 ng/ml (C(max)), 51,221.08 ng h/ml (AUC(0-infinity)) and 48.66% (absolute bioavailability), respectively. These results indicate that the oral bioavailability of GT-glu is greater than that of GT. PMID- 17280809 TI - Dermatopharmacokinetics of salicylate following topical injection in rats: effect of osmotic pressure and injection volume on salicylate disposition. AB - Using advanced topical formulations containing potential chemical enhancer(s) or physical penetration-enhancing tools capable of delivering entrapped drug(s) directly into skin tissues with little influence of the stratum corneum barrier, local and systemic drug disposition may be markedly similar to direct injection into the skin and muscle. The objective of this study is to investigate the dermatopharmacokinetics and systemic drug disposition after topical application and topical injection. Salicylate (SA) disposition in the skin and muscle as administration sites, and in the systemic circulation were evaluated following intracutaneous (i.c.) injection of an isotonic solution of SA-Na (dose; 3.08 micromol). Subcutaneous (s.c.) and intramuscular (i.m.) injection were also evaluated for comparison. Dermatopharmacokinetics and systemic disposition of SA after i.c. and s.c. injections were analyzed using a 4-compartment model consisting of skin, muscle, and central and peripheral compartments, whereas SA disposition after i.m. injection was analyzed using a 3-compartment model consisting of muscle, and central and peripheral compartments. Moreover, the absorption rate constant of SA after i.c. injection (0.073 min(-1)) was slightly lower than that after s.c. injection (0.083 min(-1)), and much lower than that after i.m. injection (0.327 min(-1)). In addition, higher osmolarity and a larger volume of SA-Na injectant increased the retention of SA in the skin and decreased the absorption rate to the systemic circulation after i.c. injection. The effect of injection volume on SA disposition after i.c. injection was not so marked compared with that of osmotic pressure. These results are useful to design an injection-type topical delivery system. PMID- 17280810 TI - Disentangling the effects of Tourette syndrome and attention deficit hyperactivity disorder on cognitive and behavioral phenotypes. AB - Eighty participants (62 males; 18 females; age range: 6-16 years) took part in the study, comprising four groups of 20 subjects each: TS-only, ADHD-only, TS+ADHD, controls. The age distributions, did not differ significantly among the four groups. The severity of symptoms, assessed by the TSGS, did not differ significantly between the two TS groups. Standardised measures were used throughout. The "cases" (i.e. TS-only, TS+ADHD, ADHD-only) were significantly different from controls on most measures of behavior. There were also differences amongst the various clinical subgroups, with, in general, TS-only participants being similar to controls with regards to both "total behavior" ratings and cognitive testing results. A diagnosis of ADHD, either or its own or in association with TS, was associated with greater maladaptive behavior and worse cognitive functioning. With regards to affective symptoms and anxiety, the three clinical groups did not differ from each other, but each of them was more affected than the control group. One finding in our study which differed from previous literature was that TS-only patients were rated as more "delinquent" than controls by their parents: possible reasons for this are discussed. Oppositional defiant disorder (ODD) was seen in a few (2,3,3 ODD patients in each clinical group), but as numbers were small no statistics were undertaken. Family histories were in accord with both TS and ADHD being genetic disorders, but sharing an overlap in only some cases. The "additive effect" hypothesis is discussed in detail in the light of our results and recent literature. PMID- 17280811 TI - Spectroscopic studies on the interaction between silicotungstic acid and bovine serum albumin. AB - The interaction between silicotungstic acid and bovine serum albumin (BSA) was investigated using fluorescence and UV/vis. The experimental results showed that the fluorescence quenching of BSA by silicotungstic acid is a result of the formation of SiW-BSA complex; static quenching and non-radiative energy transferring were confirmed to result in the fluorescence quenching. The binding site number n, apparent binding constant K(A) and corresponding thermodynamic parameters were measured at different temperatures. The process of binding SiW molecule on BSA was a spontaneous molecular interaction procedure in which entropy increased and Gibbs free energy decreased. Hydrophobic interaction force plays a major role in stabilizing the complex. The effect of silicotungstic acid on the conformation of BSA was analyzed using synchronous fluorescence spectroscopy. PMID- 17280812 TI - Efficiency improvement for sulfated ash determination by usage of a microwave muffle furnace. AB - The usefulness of microwave muffle furnaces for increasing the efficiency of sulfated ash determination through automation was investigated. Substances critical in their behavior were selected as model substances for this purpose: megestrol acetate and a phthalazine derivative as substances with high foaming indices and azelaic acid as a substance with a high spatter index. The selection of an optimal temperature sequence in conjunction with quartz crucibles and/or with a spatter guard made of quartz filter paper made it possible to handle even these critical substances. The analysis results were comparable and reproducible in terms of classical pharmacopeia methodology. PMID- 17280813 TI - Utility of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in patients with end-stage liver disease awaiting liver transplant. AB - Cognitive impairment is common among patients with end-stage liver disease (ESLD). This study examined cognitive dysfunction in patients with ESLD using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). METHOD: 66 patients with ESLD awaiting liver transplant were recruited. Patients were evaluated with the RBANS, Peabody Picture Vocabulary Test-Revised, and Beck Depression Inventory-II. RESULTS: Patients with ESLD uniformly performed below expectations on all RBANS index scores compared to the healthy normative sample (all p's<.0001) and they also displayed a "subcortical" pattern of cognitive performance (p<.0001). Performances on RBANS attention, language, immediate memory, and total index scores were correlated with education and ethnicity (r's range=|.32-.57|; p's<.01). There was no association between performance on any of the RBANS index scores or subtests and ESLD patient characteristics. In summary, the RBANS appears to adequately characterize known patterns of cognitive dysfunction in ESLD patients. PMID- 17280814 TI - Using the relaxation oscillations principle for simple phonation modeling. AB - Well-known multimass models of vocal folds are useful to describe main behavior observed in human voicing but their principle of functioning, based on harmonic oscillation, may appear complex. This work is designed to show that a simple one mass model ruled by laws of relaxation oscillation can also depict main behavior of glottis dynamic. Theory of relaxation oscillation is detailed. A relaxation oscillation model is assessed through a numerical simulation using conventional values for tissue characteristics and subglottal pressure. As expected, raising the mass decreases the fundamental frequency and increases the amplitude of vocal fold vibration: for a mass ranging from 0.01 to 0.4 g, F0 decreased from 297.5 to 42.5 Hz and vibrational amplitude increased from 1.26 to 3.25 mm (for stiffness k=10Nm(-1), damping r=0.015 N s m(-1), and subglottal pressure=1 kPa). Stiffness value has the opposite effect. The subglottal pressure controls the fundamental frequency with a rate ranging from 20 to 50 Hz/kPa. The vibrational amplitude is also controlled linearly by subglottal pressure from 0.22 to 0.26 mm/kPa. The range of phonation threshold pressure (PTP) is close to the values currently proposed, that is, 0.1 to 1 kPa and varies with the fundamental frequency. The relaxation oscillator is a simple and useful tool for modeling vocal fold vibration. PMID- 17280815 TI - Vocal folds detect ionic perturbations on the luminal surface: an in vitro investigation. AB - The homeostasis of fluid bathing the luminal surface of the vocal folds is important for phonation and laryngeal defense. Dehydration of the respiratory tract during mouth breathing can perturb the concentration of sodium and chloride ions in surface fluid. Exposure to dry air also increases the osmolarity of airway surface fluid. We hypothesized that viable vocal fold epithelium would detect changes in the ionic and osmotic composition of fluid on the luminal surface. Therefore, we examined bioelectric responses of vocal folds exposed to physiologically real, luminal ionic and osmotic challenges in vitro. The study used randomized factorial design with experimental and sham control groups. Fifty native ovine vocal folds were exposed to five challenges (ionic, osmotic, combined ionic-osmotic, and sham) on the luminal surface. Bioelectric measures of potential difference (PD), short-circuit current (I(SC)), and tissue resistance were assessed at prechallenge baseline, during challenge, and after removal of challenge. Ionic and combined ionic-osmotic challenges reduced PD and I(SC) (P<0.01). These reductions depended on the nature of the ionic challenge, were observed within 10 minutes, lasted for the duration of exposure, and were reversible after removal of the challenge. Conversely, sham or osmotic challenge did not alter bioelectric parameters over time (P>0.05). Viable ovine vocal fold epithelia detect ionic perturbations to the luminal surface. This sensitivity to luminal ionic challenge may be necessary to maintain the homeostasis of surface fluid. PMID- 17280817 TI - Contemporary commercial music. PMID- 17280816 TI - Hoarseness due to bamboo nodes in patients with autoimmune diseases: a review of literature. AB - SUMMARY: This is a retrospective report on clinical features, laryngoscopic examinations, and follow-up markers of laryngeal manifestation described as bamboo nodes in three female patients with transverse cystic lesions of the vocal folds, treated with logopedic therapy. This study examines logopedic and phoniatric aspects in patients with submucosal "bamboo joint-like nodes" of both vocal folds, and reveals an improvement of different voice quality features after conservative traditional voice therapy. There still exists no standard treatment regimen in patients with rheumatoid disease of the larynx; a lack of consensus is most evident in the role of voice therapy. We would like to emphasize the favorable impact of logopedic therapy in benign laryngeal disorders with underlying autoimmune diseases. PMID- 17280818 TI - Feminine after cricothyroid approximation? AB - A number of studies have evaluated the effectiveness of a cricothyroid approximation (CA) in creating a more female voice in male-to-female transsexuals (MFTs) from an acoustic perspective. An increase in pitch is of little value, however, unless it accurately indicates listeners' perceptions of gender. The purpose of this study was to further investigate the effectiveness of a CA in feminizing the voice from a perceptual perspective. Video recordings of nine MFTs, nine nontranssexual males (NTMs), and nine nontranssexual females (NTFs) were presented twice to the panel of judges in a randomized order: first auditory only (only hearing a subject's speech) and subsequently audiovisual (hearing and seeing a subject's speech). The panel of judges, 42 students (21 female, 21 male) from different disciplines, rated the participants' voices on a 100-mm visual analog scale with "very male" and "very female" as left and right extremes, respectively. The group of MFT obtained scores that were situated in between those of the NTM and the NTF, both for the auditory only and the audiovisual mode of presentation. Perception of femaleness significantly correlated with average fundamental frequency for both modes of presentation. It can be concluded that a CA approximation is a viable option to raise the voice pitch in MFTs but that this surgery alone may not be sufficient to create a voice that is perceived as a totally female. PMID- 17280819 TI - Vocal tremor and vibrato in the same person: acoustic and electromyographic differences. AB - The goal of this case study was to measure and describe differences between vocal vibrato and essential tremor of the voice in one individual who exhibited both types of modulation. Recordings of spoken and sung vowels produced by the same individual at three effort levels were examined via analysis of acoustic and laryngeal electromyographic (LEMG) signals. Modulation rate, periodicity, and spectral measures of both audio and muscle activation signals revealed generally slower, more prominent, and more regular patterns in sung than in spoken conditions. There was not always a clear correspondence between LEMG and acoustic measures, but both showed differences between the vibrato and tremor of this individual, suggesting differences in the neural bases of these modulations. PMID- 17280821 TI - Live observation of excystment in the spirotrich ciliate Meseres corlissi. AB - Excystment of Meseres corlissi Petz and Foissner 1992 was observed by light microscopy. Excysting cells were first recognized by the appearance of a non pulsating vacuole. With increasing size of this vacuole, the outer cyst wall ruptured, creating a narrow slit. The emerging protoplast was enclosed by an inner flexible membrane. Oral membranelles were faintly visible, but inactive at this stage. Within the next hour, oral membranelles and a pulsating vacuole became active, and the ciliate started to rotate. During a phase of rapid movement, the flexible membrane became wider and thinner. Finally, it burst open and released the now fully differentiated ciliate. The emergence of M. corlissi from the cyst is similar to descriptions in the literature for Didinium nasutum, Nassula ornata, Tillina magna and several stichotrich ciliates. PMID- 17280820 TI - Nanoparticulate delivery system for insulin: design, characterization and in vitro/in vivo bioactivity. AB - Insulin-loaded alginate-dextran nanospheres were prepared by nanoemulsion dispersion followed by triggered in situ gelation. Nanospheres were characterized for mean size and distribution by laser diffraction spectroscopy and for shape by transmission electron microscopy. Insulin encapsulation efficiency and in vitro release were determined by Bradford protein assay and bioactivity determined in vitro using a newly developed Western blot immunoassay and in vivo using Wistar diabetic rats. Nanospheres ranged from 267 nm to 2.76 microm in diameter and demonstrated a unimodal size distribution. Insulin encapsulation efficiency was 82.5%. Alginate-dextran particles suppressed insulin release in acidic media and promoted a sustained release at near neutral conditions. Nanoencapsulated insulin was bioactive, demonstrated through both in vivo and in vitro bioassays. PMID- 17280822 TI - Drug delivery: a Canadian perspective. 25 years of innovative drug delivery research. PMID- 17280823 TI - Chitosan microspheres enhance the immunogenicity of an Ag85B-based fusion protein containing multiple T-cell epitopes of Mycobacterium tuberculosis. AB - To develop novel delivery system for tuberculosis (TB) subunit vaccine, biodegradable chitosan microspheres were prepared and used to deliver a fusion protein, Ag85B-MPT64(190-198)-Mtb8.4 (AMM for short), made from three Mycobacterium tuberculosis genes. AMM-loaded microspheres were first characterized for their morphology, size, zeta potential, loading efficiency, and in vitro release of AMM. C57BL/6 mice were immunized at weeks 1, 3 and 5 subcutaneously with AMM formulated in chitosan microspheres, in incomplete Freund's adjuvant (IFA), or in phosphate-buffered saline (PBS), respectively. Three weeks after the last immunization, humoral and cell-mediated immune responses were examined. It was shown that the microspheres bound AMM quite efficiently (loading efficiency: >99%). AMM-loaded chitosan microspheres were observed as aggregated shapes with the average particle size of 5.78+/-0.65 microm and zeta potential of 32.77+/-1.51 mV. In vitro release studies revealed that only small amount of antigen was released in 16 days. Following subcutaneous administration, splenocytes immunized with AMM in chitosan microspheres produced higher levels of IFN-gamma compared to administration of AMM in PBS upon stimulation with Ag85B and synthetic peptide MPT64(190-198). The levels of Ag85B specific IgG (H+L), IgG1 and IgG2a in sera of mice immunized with AMM in chitosan microspheres were also higher than those with AMM in PBS. These results indicate that chitosan microspheres when used as a carrier for fusion protein AMM could elicit strong humoral and cell-mediated immune responses. PMID- 17280824 TI - Mycological Research: instructions and guidelines for authors. AB - Instructions and guidelines for authors submitting papers to Mycological Research are provided. The journal is international and covers all fields of mycology, both fundamental and applied. It publishes news items, reviews, original papers, and book reviews. Contributions should be of interest to a wide spectrum of mycologists or make significant novel contributions. Papers with particularly exciting results are fast-tracked and prioritized for publication. Submission must be made online via the Elsevier Editorial System (ees.elsevier.com/mycres); hard copy submissions are no longer accepted. Information is provided on: scope and timeliness; submission of articles; manuscript preparation; tables; illustrations; spellings, numbers, chemical symbols, and abbreviations; voucher material; molecular data; taxonomic data; references; the decision-making process; copyright; author's copies; proofs; and further questions. PMID- 17280825 TI - Effects of diesel exhaust particles on human lung epithelial cells: an in vitro study. AB - Atmospheric particulate matter (PM), an ingredient of urban pollution matter, is a mixture of solid and liquid particles differing in origin, dimension and composition. There is big concern about inhaled PM in urban areas, especially due to its adverse effects on the respiratory system. Diesel exhaust particulate (DEP), which constitutes the major part of PM, is characterized by a carbonic mixture composed of approximately 18,000 different high-molecular-weight organic compounds. Diesel engines release 10 times the amount of NO(2) aldehydes and breathable PM compared to unleaded gasoline engines and more than 100 times that produced by catalysed gasoline engines; these data gain great significance when taken into account the fact that diesel-powered vehicles are becoming more and more popular. DEP polyaromatic hydrocarbons (PAH), once deposited on airways mucous surfaces easily pass through epithelial cells (ECs) membranes, bind themselves to cytosolic receptors and then affect cell growth and differentiation. Human lung epithelial cells and macrophages engulf DEP, this resulting in increased proinflammatory cytokines release (IL-6, IL-8 and GM-CSF). We investigated the biological effects of DEP-PM on the human lung EC line A549. Light microscopy analysis suggested the presence of cell wall alterations, and provided evidence of PM internalization and cytoplasmic vacuolization. Following PM stimulation, nuclei also were seen undergo clear gross morphological modifications. Immunocytochemistry was used to detect intracytoplasmic IL-6 and IL-8 expression. PMID- 17280826 TI - Local waste management constraints and waste administrators in China. AB - Local level waste authorities and their officials directly interact and serve the people on behalf of higher governments. Given the influential positions they have on the quality of life of the citizens, these local waste authorities deserve more attention from researchers. This study throws light on the factors related to local waste management and administrators that have caused waste management failures in three mainland Chinese cities. Based on a survey conducted in 2002 2003, it was found that waste administrators in these cities are not professionally competent in their jobs and they are also not confident in using economic instruments to address waste management issues in their cities. These local waste authorities are generally under-funded, and funding politics has to some extent eroded the incentives to carry out the instructions of higher waste authorities. The community at large also does not respect local waste management work. The residents frequently litter, are unobservant of waste collection times and are unwilling to pay for waste collection service. All of these are handicapping environmentally sound waste management. PMID- 17280827 TI - Logistical management and private sector involvement in reducing the cost of municipal solid waste collection service in the Tubas area of the West Bank. AB - This paper addresses the problems of the municipal solid waste (MSW) collection system in the Tubas district of Palestine. More specifically, it addresses the often-voiced concerns pertaining to low efficiency as well as environmental problems. This was carried out through a systematic methodological approach. The paper illustrates how a private company applied a logistical management strategy, by rescheduling the MSW collection system, reallocating street solid waste containers and minimizing vehicle routing. The way in which the MSW collection timetable was rescheduled decreased the operating expenses and thus reduced MSW collection costs. All data needed to reschedule the collection timetable and optimize vehicle routing were based on actual field measurements. The new MSW collection timetable introduced by a private company was monitored for a period of a month. The new system resulted in an improvement in the MSW collection system by reducing the collection cost to a level that is socially acceptable (US dollars 3.75/family/month), as well as economically and environmentally sound. PMID- 17280828 TI - Characterization of Vitamin D insensitive prostate cancer cells. AB - The antitumor effects of 1,25-dihydroxyvitamin D(3) (calcitriol) are being exploited for prevention and treatment of prostate cancer (CaP). These studies examined the antiproliferative effects of calcitriol in primary cell cultures derived from transgenic adenocarcinoma of mouse prostate (TRAMP) mice chronically treated with calcitriol (20 microg/kg) or vehicle 3x/week from 4 weeks-of-age until palpable tumors developed. This is a report on the response of two representative control (Vitamin D naive, naive) and calcitriol-treated (Vitamin D insensitive, VDI) cells to calcitriol. VDI cells were less sensitive to calcitriol based on less cell growth inhibition and less inhibition of DNA synthesis as measured by MTT and BrdU incorporation assays. Similarly, VDI cells were less sensitive to growth inhibition by the vitamin analog, 19-nor-1alpha,25 dihydroxyvitamin D(2) (paricalcitol). There was no change in apoptosis following treatment of naive and VDI cells with calcitriol. Vitamin D receptor (VDR) expression was up-regulated by calcitriol in both naive and VDI cells. In addition, calcitriol induced the Vitamin D metabolizing enzyme, 24-hydroxylase (cyp24) mRNA and enzyme activity similarly in naive and VDI cells as measured by RT-PCR and HPLC, respectively. In summary, VDI cells are less responsive to the antiproliferative effects of calcitriol. Understanding Vitamin D insensitivity will further clinical development of Vitamin D compounds for prevention and treatment of CaP. PMID- 17280829 TI - Safety and effectiveness of prophylactic gastrostomy tubes for head and neck cancer patients undergoing chemoradiation. AB - BACKGROUND: We would like to assess the safety and effectiveness of prophylactic percutaneous endoscopic gastrostomy (PEG) tube feedings during concurrent chemoradiation for head and neck cancer. METHODS: Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. All patients underwent PEG tube placement prior to the treatment because of the expected mucositis. Gastrostomy tubes were removed following treatment when the patients were able to resume oral feedings without aspiration. RESULTS: Between March 1999 and 2006, 104 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. One patient declined placement of gastrostomy tube. Ninety patients (86%) developed grade 3-4 mucositis during chemoradiation. Five patients died during treatment from aspiration pneumonia and sepsis. One hundred two patients lost weight during treatment. The mean and median weight loss during concurrent therapy was, respectively, 8.5 and 8 kg (1-23.5 kg). Following treatment, tube feedings were continued 1-41 months (mean: 8 months; median: 5 months) because of continued weight loss, chronic dysphagia, or aspiration. At a median follow-up of 19 months (1-62 months), no patient developed serious complications from tube feedings. CONCLUSION: Dysphagia resulting from the severe mucositis produced severe weight loss, despite tube feedings. Gastrostomy tube feedings are safe. Gastrostomy tubes should be placed prophylactically for patients undergoing chemoradiation for head and neck cancer. PMID- 17280830 TI - Spore detection in aerobic granules by different dipicolinic acid releasing methods. AB - This work aimed at developing a procedure for spore quantification. Spore content was determined by analyzing dipicolinic acid (dpa) extracted from aerobic granules by 13 methods. Concentrated HCl was able to release dpa completely. Results showed that dpa constituted 33.7 mg per g SS, meaning that about 337 mg per g SS were spores, not the normal vegetative cells. PMID- 17280831 TI - Powdered activated carbon augmented activated sludge process for treatment of semi-aerobic landfill leachate using response surface methodology. AB - This study was conducted to investigate aerobic biodegradation of semi-aerobic leachate with and without powdered activated carbon (PAC) addition. The experiment involved operating two 16L laboratory-scale activated sludge reactors in parallel at room temperature and adjusted to pH 6.5+/-0.5. One of the reactors was supplemented with PAC of 75-150microm size to observe its effect on semi aerobic leachate biodegradation. Three hydraulic retention times (0.92, 1.57 and 2.22 d) and influent COD concentrations (750, 1800 and 2850mg/L) were applied in a factorial design for this study. The results showed enhanced reactor performance due to PAC addition with higher COD, colour and ammoniacal nitrogen removals. The PAC augmented reactor also had higher concentrations of NO(2)-N and NO(3)-N consequent of greater degree of nitrification. PMID- 17280832 TI - Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid with D-phenylalanine for colon specific drug delivery in inflammatory bowel disease. AB - Mutual azo prodrug of 5-aminosalicylic acid with d-phenylalanine was synthesized by coupling D-phenylalanine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5 aminosalicylic acid, whereas in phosphate buffer (pH 7.4) only 15% release was observed over a period of 7h. In rat fecal matter the release of 5-aminosalicylic acid was almost complete (85%), with a half-life of 160.1 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid. PMID- 17280833 TI - Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR. AB - 4-Amino-5,6-biaryl-furo[2,3-d]pyrimidines were identified as potent non-selective inhibitors of Lck. A novel, divergent, and practical synthetic route was developed to access derivatives from bifunctional intermediates. Lead optimization was guided by X-ray crystallographic data, and preliminary SAR led to the identification of compounds with improved cellular potency and selectivity. PMID- 17280834 TI - The insulin and EGF receptor structures: new insights into ligand-induced receptor activation. AB - The insulin receptor (IR) and epidermal growth factor receptor (EGFR; also known as ErbB) families exhibit similarities in the composition of their ectodomains. The past five years have seen structures determined for all members of the EGFR family including some complexes with ligand or monoclonal antibody fragments. These structures have led to a clearer understanding of their mechanism of activation and inhibition. By contrast, obtaining equivalent understanding of the IR family has lagged behind. However, within the past year, structures of partial and complete ectodomains of the IR have been published that show that the extracellular region of the receptor adopts an unexpected 'inverted V' conformation relative to the cell membrane. This is very different from the folded-over (tethered) conformation of the unactivated EGFR and provides insight into the potential mechanism of activation of the IR. PMID- 17280835 TI - Synthesis and antiplasmodial activity of new N-[3-(4-{3-[(7-chloroquinolin-4 yl)amino]propyl}piperazin-1-yl)propyl]carboxamides. AB - The parallel acylation of N-{3-[4-(3-aminopropyl)piperazin-1-yl]propyl}-7 chloroquinolin-4-amine with polymer-bound carboxylic acids opened straightforward access to novel aminoquinolines with activity against Plasmodium falciparum strains in vitro. Using this amino scaffold prepared in solution and polymer bound carboxylic, we have synthesized a series of 29 new compounds in good to excellent yield and purity. Biological evaluation included determination of the activity against a chloroquine (CQ) sensitive strain and a CQ resistant mutant. Most of the novel structures presented here displayed activity against both strains in the lower nanomolar range, four compounds showed an at least fourfold increase in the ratio of inhibition of CQ resistant to sensitive strains over CQ itself. These results suggest that this derivatization technique is a useful method to speed up structure-activity relationship studies on aminoquinolines toward improved activity versus CQ resistant strains of P. falciparum in vitro. PMID- 17280836 TI - Nitric oxide promotes the wound-healing response of potato leaflets. AB - Nitric oxide (NO) is an essential regulatory molecule in several developmental and (patho) physiological processes. In this work, it is demonstrated that NO participates in the wound-healing response of potato leaves. The experimental approaches showed that the deposition of the cell-wall glucan callose was induced by the application of the NO donor sodium nitroprusside (SNP), and such induction was additive to the wound-induced callose production. Additionally, the expression of wound-related genes as phenylalanine ammonia-lyase (PAL) and extensin showed an accumulation of their transcript levels by SNP treatment. Moreover, the SNP-mediated increase of the PAL transcript level was additive to the induction mediated by wounding. These results indicate that increased levels of NO might potentiate the healing responses in plants leading to a rapid restoration of the damaged tissue. PMID- 17280837 TI - The effect of preoperative atrial fibrillation on survival following mitral valve repair for degenerative mitral regurgitation. AB - OBJECTIVE: There is conflicting evidence with regard to the impact of preoperative atrial fibrillation (AF) on the post mitral valve (MV) repair on the early and late outcome. METHODS: A total of 349 patients undergoing various MV repair procedures for degenerative mitral regurgitation (MR) between 1997 and 2003 were studied. Preoperatively, 152 (44%) of these patients were in AF and 197 (56%) patients were in sinus rhythm (SR). The clinical features and the outcome in these two cohorts of patients were compared. RESULTS: The patients in the AF group were older than their counterparts in the SR group (66+/-7 vs 62+/-9 years) (p=0.01), had a higher mean NYHA class score (2.4+/-0.6 vs 2.2+/-0.7) (p=0.04) and were more likely to have impaired left ventricular function (60% vs 36%) (p<0.0001). A similar proportion of patients in the AF (38%) and SR (30%) groups had additional cardiac surgical procedures (p=0.12). Operative mortality was 3.9% in AF group versus 0.5% in SR group (p=0.04), and operative morbidity was 27% versus 17%, respectively (p=0.03). At latest follow up, 4% of patients that were in SR preoperatively developed AF; conversely, 2% of the patients in the AF group converted to SR. The rates of recurrent grade II or III MR (4% vs 5%) (p=0.8) and MV re-operation (2.6% vs 2.5%) (p=1.0) were similar in the AF and SR groups. Kaplan-Meier survival at 7 years was 75+/-6% versus 90+/-3% (p=0.005). On Cox proportional hazards regression model, impaired LV function [(p=0.02), hazard ratio 0.25 (95% confidence intervals (C.I.) 0.078-0.84)] and AF [(p=0.03), hazard ratio 2.70 (95% C.I. 1.09-6.68)] were significant adverse predictors of survival. CONCLUSIONS: This study shows that in patients undergoing MV repair for degenerative MR, preoperative AF has a major negative impact on the early and late survival. PMID- 17280838 TI - Normal temperature and flow: are the 'physiological' values so scary? PMID- 17280839 TI - The effect of the eye's surface topography on the total irradiance of ultraviolet radiation on the inner canthus. AB - Basal cell carcinoma is the most commonly occurring skin cancer in sub tropical climates. The link between ultraviolet radiation (UVR) and basal cell carcinomas (BCC) is strong. Numerous studies have investigated the spatial distribution of BCCs over the head and neck region and the relative UVR dose, with little or no correlation found between the UVR dose and occurrence rates. This is particularly noted in the inner canthus region. The inner canthus' field of view is restricted by the eye brow ridge, eye orbit and the cheek bone. Yet, the occurrence rate here of BCC's when compared to other regions that are more directly exposed to the environment is significantly higher. A possible causal effect for the increase in occurrence rate in this region is the focussed reflection of UVR from the tear film surface associated with the eye not previously considered in earlier studies. This paper investigates the potential for the surface topography of the eye to reflect focussed radiation towards the inner canthus using a ray tracing programme where the analysis is conducted at a cellular level. Defined hot spots, or striations, of increased irradiation were evidenced across the surface of the inner canthus. This increase in irradiation was not observed with macroscopic detectors which also possibly explain why this increased dose has not previously been detected during environmental measurements with large detectors on manikins or humans. PMID- 17280841 TI - What is the role of Toll-like receptors in bacterial infections? AB - Innate immunity relies on signalling by Toll-like receptors (TLRs) to alert the immune system of the presence of invading bacteria. TLR activation leads to the release of cytokines that allow for effective innate and adaptive immune responses. However, the contribution of different TLRs depends on the site of the infection and the pathogen. This review will describe the involvement of TLRs in the development of three different bacterial infections as well as our current understanding of the role of TLRs during microbial pathogenesis. PMID- 17280840 TI - Effect of DL-nebivolol, its enantiomers and metabolites on the intracellular production of superoxide and nitric oxide in human endothelial cells. AB - Nebivolol, a third generation selective beta(1)-adrenoceptor (beta(1)-AR) antagonist, has been reported to reduce intracellular oxidative stress and to induce the release of nitric oxide (NO) from the endothelium. Nebivolol is also subjected to a complex metabolic process where glucuronidation, aromatic and alicyclic hydroxylation are the major pathways leading to several metabolites. We have studied the effect of nebivolol, its enantiomers and metabolites on intracellular oxidative stress and NO availability in human umbilical vein endothelial cells (HUVECs). Furthermore, since the receptors involved in this endothelial effect of nebivolol remain controversial, we have studied this matter by the use of antagonists of beta-AR. dl-Nebivolol, d-nebivolol and l-nebivolol significantly reduced the formation of reactive oxygen species (ROS) and superoxide induced by oxidized-low density lipoprotein (ox-LDL), although the racemic and l-form were significantly more active than d-nebivolol in this activity. A marked decrease in the availability of intracellular NO was found in HUVECs exposed to ox-LDL and this parameter was normalized by the prior incubation with dl-nebivolol, d-nebivolol and l-nebivolol; the effect of racemate was mainly mimicked by its l-enantiomer. eNOS activity significantly increased by a 5-min contact of HUVECs with dl-nebivolol and l-nebivolol, but not with d nebivolol, and a similar pattern was observed when the intracellular calcium increase was measured. The metabolites A2, A3', A12 and A14 but not A1, A3 and R 81,928, derived from different metabolic pathways, retained the antioxidant activity of the parent racemic compound dl-nebivolol, reducing the intracellular formation of ROS and superoxide. The effects of dl-nebivolol on intracellular formation of NO, eNOS activity and intracellular Ca(2+) were partially antagonized by the antagonists of beta(1-2)-AR nadolol or by the beta(3)-AR antagonist SR59230A and further antagonized by their combination or by (beta(1-2 3)-AR antagonist bupranolol. In conclusion, this study shows that the NO releasing effect of nebivolol is mainly due to its l-enantiomer; the racemate and its enantiomers possess a remarkable antioxidant activity that contributes to its effect on the cellular NO metabolism and the activation of beta(3)-AR through a calcium dependent pathway is involved in the mechanisms leading to the NO release. PMID- 17280843 TI - Distribution of hepatitis E virus infection and its prevalence in pigs on commercial farms in Spain. AB - A survey to detect antibodies against hepatitis E virus (HEV) was undertaken on 41 Spanish pig farms using an indirect enzyme-linked immunosorbent assay (ELISA). Forty of the farms (97.6%) were positive for anti-HEV IgG antibodies, while 34/41 (82.9%) had IgM positive animals. The highest proportion of IgG positive pigs comprised the adult sows (45/74, 60.8%; P=0.01), followed by young piglets aged 3 6 weeks (79/218, 36.2%). IgM positive pigs were more frequently found to be those animals > or = 12 weeks of age (P<0.001). In a second part of the study, the age distribution of the infection on one HEV infected farm was studied by combining the ELISA test with reverse transcription polymerase chain reaction (RT-PCR). On this farm, viraemia was mostly detected in animals aged 8-12 weeks and faecal shedding of HEV was detected in pigs of the same age. All HEV sequences corresponded to genotype 3. The study confirmed that HEV is spread in pigs in Spain and is probably endemic in many farms. PMID- 17280842 TI - The Fus3/Kss1 MAP kinase homolog Amk1 regulates the expression of genes encoding hydrolytic enzymes in Alternaria brassicicola. AB - Mitogen-activated protein (MAP) kinases have been shown to be required for virulence in diverse phytopathogenic fungi. To study its role in pathogenicity, we disrupted the Amk1 MAP kinase gene, a homolog of the Fus3/Kss1 MAP kinases in Saccharomyces cerevisiae, in the necrotrophic Brassica pathogen, Alternaria brassicicola. The amk1 disruption mutants showed null pathogenicity on intact host plants. However, amk1 mutants were able to colonize host plants when they were inoculated on a physically damaged host surface, or when they were inoculated along with nutrient supplements. On intact plants, mutants expressed extremely low amounts of several hydrolytic enzyme genes that were induced over 10-fold in the wild-type during infection. These genes were also dramatically induced in the mutants on wounded plants. These results imply a correlation between virulence and the expression level of specific hydrolytic enzyme genes plus the presence of an unidentified pathway controlling these genes in addition to or in conjunction with the Amk1 pathway. PMID- 17280845 TI - A single-scan method for measuring flow along an arbitrary direction. AB - In this article, we demonstrate a single-scan method to measure an average flow velocity vector along an arbitrary direction. This method is based on the MMME sequence and utilizes static and pulsed magnetic field gradients along multiple directions for the optimal determination of flow velocity components in three dimensional space. Experimentally measured average flow velocities from the flow induced phase shift with a single-scan MMME sequence show excellent agreements with the known flow rate, and the signal decay of each echo due to a velocity distribution is also quantitatively verified with known laminar flow patterns. PMID- 17280844 TI - The role of (15)N CSA and CSA/dipole cross-correlation in (15)N relaxation in solid proteins. AB - The influence of the (15)N CSA on (15)N longitudinal relaxation is investigated for an amide group in solid proteins in powder form under MAS. This contribution is determined to be typically 20-33% of the overall longitudinal relaxation rate, at 11.74 and 16.45 T, respectively. The improved treatment is used to analyze the internal dynamics in the protein Crh, in the frame of a motional model of diffusion in a cone, using the explicit average sum approach. Significant variations with respect to the determined dynamics parameters are observed when properly accounting for the contribution of (15)N CSA fluctuations. In general, the fit of experimental data including CSA led to the determination of diffusion times (tau(w)) which are longer than when considering only an (15)N-(1)H dipolar relaxation mechanism. CSA-Dipole cross-correlation is shown to play little or no role in protonated solids, in direct contrast to the liquid state case. PMID- 17280846 TI - Cross- and axial-peak intensities in 2D-SLF experiments based on cross polarization--the role of the initial density matrix. AB - Simulations and experiments on simple oriented systems have been used to estimate the relative ratio of cross-peak to axial-peak intensities in 2D-SLF experiments based on dipolar oscillations during cross-polarization (CP). The density matrix prior to dipolar evolution is considered and for an isolated spin pair, it is shown that direct calculations of the ratios match well with simulations and experimental results. Along with the standard CP pulse sequence, two other pulse sequences namely CP with polarization inversion (PI-CP) and another novel variation of the standard CP experiment (EXE-CP) reported recently have been considered. Inclusion of homonuclear dipolar coupling has been observed to increase the axial-peak intensities. In combination with Lee-Goldburg (LG) decoupling, experiments on an oriented liquid crystalline sample have been carried out and the performance of the pulse schemes have been compared. The applicability of the new pulse sequence for different samples and different nuclei is discussed. Such studies are expected to lead to a better understanding of the experiments and to the design of useful pulse sequences. PMID- 17280848 TI - Pediatric periodic alternating gaze deviation with midline cerebellar disease. AB - Periodic alternating gaze deviation is a rare eye movement disorder characterized by a horizontal eccentric gaze that lasts for a few minutes in one direction before reversing to the opposite direction with the cycle repeating itself. This report details the findings of an affected infant with cerebellar hypoplasia in the context of previously reported cases and supports the idea that the phenomenon typically is caused by cerebellar midline disease. PMID- 17280847 TI - Construction and calibration of a 50 T/m z-gradient coil for quantitative diffusion microimaging. AB - q-Space imaging is capable of providing quantitative geometrical information of structures at cellular resolution. However, the size of restrictions that can be probed hinges on available gradient amplitude and places very high demands on gradient performance. In this work we describe the design and construction of a small, high-amplitude (50 T/m) z-gradient coil, interfaced with a commercial 9.4 T microimaging system. We also describe a method to calibrate the coil for quantitative measurements of molecular diffusion at very high-gradient amplitudes. Calibration showed linear current response up to 50 T/m, with a gain=1.255 T/m/A. The z-gradient coil was combined with the commercial x- and y gradients for tri-axial imaging, and its performance was demonstrated by ADC maps of free water and by q-space experiments on water sequestered around polystyrene microspheres (4.5 microm diameter), which showed the expected diffraction peak. In addition, diffusion-weighted images of a fixed mouse spinal cord illustrated the capability of this coil for quantitative imaging of tissue microstructure. PMID- 17280849 TI - Combining recessions (nystagmus and strabismus) with tenotomy improved visual function and decreased oscillopsia and diplopia in acquired downbeat nystagmus and in horizontal infantile nystagmus syndrome. AB - PURPOSE: To investigate the effects of combined tenotomy and recession procedures on both acquired downbeat nystagmus and horizontal infantile nystagmus. METHODS: Patient 1 had downbeat nystagmus with a chin-down (upgaze) position, oscillopsia, strabismus, and diplopia. Asymmetric superior rectus recessions and inferior rectus tenotomies reduced right hypertropia and rotated both eyes downward. Patient 2 had horizontal infantile nystagmus, a 20 degrees left-eye exotropia, and alternating (abducting-eye) fixation. Lateral rectus recessions and medial rectus tenotomies were performed. Horizontal and vertical eye movements were recorded pre- and postsurgically using high-speed digital video. The eXpanded Nystagmus Acuity Function (NAFX) and nystagmus amplitudes and frequencies were measured. RESULTS: Patient 1: The NAFX peak moved from 10 degrees up to primary position where NAFX values improved 17% and visual acuity increased 25%. Vertical NAFX increased across the -10 degrees to +5 degrees vertical range. Primary position right hypertropia decreased approximately 50%; foveation time per cycle increased 102%; vertical amplitude, oscillopsia, and diplopia were reduced, and frequency was unchanged. Patient 2: Two lateral, narrow high-NAFX regions (due to alternating fixation) became one broad region with a 43% increase in primary position (acuity increased approximately 92.3%). Diplopia amplitude decreased; convergence and gaze holding were improved. Primary-position right exotropia was reduced; foveation time per cycle increased 257%; horizontal-component amplitude decreased 45.7%, and frequency remained unchanged. CONCLUSIONS: Combining tenotomy with nystagmus or strabismus recession procedures increased NAFX and visual acuities and reduced diplopia and oscillopsia in downbeat nystagmus and infantile nystagmus. PMID- 17280850 TI - Bilateral incyclotorsion, absent facial nerve, and anotia: fellow travelers in Mobius sequence or oculoauriculovertebral spectrum? AB - We report a patient with bilateral incyclotorsion, asymmetric facial palsy, monocular depression deficiency, and unilateral Type 3 Duane syndrome, along with contralateral anotia and a midline cleft palate. A dysplastic middle ear cavity and unilateral absence of the facial nerve were noted on magnetic resonance imaging scanning. The differential diagnosis includes Mobius sequence, oculoauriculovertebral spectrum, and a congenital cranial dysinnervation disorder. PMID- 17280851 TI - How to measure slab-off and reverse slab prism in spectacle lenses. AB - It is well known that new spectacle lenses for the correction of anisometropia can induce diplopia with reading. The difference in the powers of the lenses induces a net prismatic effect that can cause double vision through off-center areas of the lenses. This is particularly bothersome when patients try to read, often noting vertical double vision in attempted downgaze, especially through multifocal add segments. This induced prismatic effect can be compensated at one level of downgaze by the use of slab-off or reverse slab prism. Typically the slab-off correction is ground into the stronger minus, or weaker plus lens. Reverse slab is ground into the weaker minus, or stronger plus, lens. Unfortunately, determining the amount of slab-off prism already incorporated into spectacle lenses is nonintuitive and inconvenient. This usually requires the use of a lens clock, which is not widely accessible to many ophthalmology practices. A simple technique, described in the past but poorly known, is illustrated here for quickly measuring slab-off and reverse slab prism prescription lenses in the clinic with a common manual lens meter. PMID- 17280853 TI - Periosteal fixation in third nerve palsy. PMID- 17280854 TI - Strabismus after endoscopic third ventriculostomy. AB - Until recently, the treatment of choice for noncommunicating hydrocephalus included the use of valve-regulated shunts such as the ventriculoperitoneal shunt. High failure rates and multiple complications have led neurosurgeons to use other techniques. Endoscopic third ventriculostomy (ETV) is becoming popular as treatment for noncommunicating hydrocephalus when standard shunts have failed.(1) We present 2 adolescents who developed exotropia, hypertropia, and diplopia after endoscopic third ventricle surgery. PMID- 17280855 TI - Superior oblique myokymia: efficacy of medical treatment. AB - PURPOSE: Superior oblique myokymia (SOM) is an uncommon disorder characterized by episodic monocular oscillopsia. Several medications have been reported to be of benefit for some patients with this condition, but the efficacy of medical treatment has not been well established and little long-term follow-up data are available. The purpose of this study was to better clarify the role of medical therapy in the management of SOM. METHODS: A retrospective review of patients with this disorder seen in an outpatient neuro-ophthalmology clinic. The diagnosis of SOM was based on a history of episodic unilateral oscillopsia with or without torsional diplopia. Twenty-seven patients with SOM were identified. Twenty of these were treated medically and these formed the basis of the study. Follow-up interval ranged from 1 to 12.5 years (mean, 6.5 years). The main outcome measure was relief of oscillopsia. RESULTS: Fifteen of the 18 patients treated with carbamazepine (83%) reported some benefit, 6 of whom continue to do well on medication 9 months to 5 years later. In four patients improvement was only transient and in five others treatment was subsequently discontinued for various reasons. In addition, one patient had sustained benefit from phenytoin, one from propranolol, and one from propranolol plus valproic acid. We found no treatment success with baclofen. Overall, nine patients (45%) enjoy sustained benefit unassociated with adverse side effects. CONCLUSIONS: In contrast to previous reports emphasizing the efficacy of surgery for SOM, our data demonstrate the potential benefits of medical treatment for patients with this disorder. PMID- 17280856 TI - Spontaneous separation of idiopathic epiretinal membrane in a 7-year-old child. AB - Epiretinal membrane is occasionally encountered in children; it is usually idiopathic but can be due to conditions such as vitreous hemorrhage or shaken baby syndrome. Though persistent adherence of the symptomatic epiretinal membrane warrants surgical intervention, spontaneous separation of the membrane has been reported. We report a case of spontaneous separation of an idiopathic epiretinal membrane in a young child. PMID- 17280858 TI - The potential influence of gastric acid secretion during fasting on digestion time in leopard sharks (Triakis semifasciata). AB - Vertebrates are known to differ in their response of gastric acid secretion during periods of fasting, yet the reasons for these differences remain unclear. Previously, continuous measurements of gastric pH in leopard sharks (Triakis semifasciata) had determined that acid secretion in this species is continuous. In order to determine if maintaining an empty acidic stomach may reduce digestion time of a subsequent meal, a simple descriptive model based on acid secretion rates was developed. In vivo gastric acid secretion rates were measured using an auto-titration technique. Acid secretion rates were pH dependent, with rates of 6.1+/-3.0 (+/-1 SD) mmol/h when gastric pH was >2.5, and 1.7+/-0.8 mmol/h when pH was 2.0-2.5. Analysis by Western blots suggests that pepsin secretion occurs within 1 h of feeding, and that there is a de-coupling of acid and pepsin secretion. The model estimates that digestion time can be reduced by 5.7+/-1.3 h and pepsin activity increased by 10-100% during that time if the stomach is acidic before feeding. Gastric acid secretion during fasting is hypothesized to reduce digestion time of a subsequent meal in frequently feeding sharks, which may be advantageous for exploiting resources that are spatially and temporally unpredictable. PMID- 17280857 TI - Evidence of binocular fusion in a 3-week-old infant with transient abducens nerve paresis. AB - We report an infant with clinical evidence of binocular fusion at 3 weeks of life. To the best of our knowledge, this is the first report providing evidence of binocularity in the first month of life. PMID- 17280859 TI - Characterization of a novel EF-hand homologue, CnidEF, in the sea anemone Anthopleura elegantissima. AB - The superfamily of EF-hand proteins is comprised of a large and diverse group of proteins that contain one or more characteristic EF-hand calcium-binding domains. This study describes and characterizes a novel EF-hand cDNA, CnidEF, from the sea anemone Anthopleura elegantissima (Phylum Cnidaria, Class Anthozoa). CnidEF was found to contain two EF-hand motifs near the C-terminus of the deduced amino acid sequence and two regions near the N-terminus that could represent degenerate EF hand motifs. CnidEF homologues were also identified from two other sea anemone species. A combination of bioinformatic and molecular phylogenetic analyses was used to compare CnidEF to EF-hand proteins in other organisms. The closest homologues identified from these analyses were a luciferin binding protein (LBP) involved in the bioluminescence of the anthozoan Renilla reniformis, and a sarcoplasmic calcium-binding protein (SARC) involved in fluorescence of the annelid worm Nereis diversicolor. Predicted structure and folding analysis revealed a close association with bioluminescent aequorin (AEQ) proteins from the hydrozoan cnidarian Aequorea aequorea. Neighbor-joining analyses grouped CnidEF within the SARC lineage along with AEQ and other cnidarian bioluminescent proteins rather than in the lineage containing calmodulin (CAM) and troponin-C (TNC). PMID- 17280860 TI - Recombinant bovine growth hormone-induced reduction of atrial natriuretic peptide is associated with improved left ventricular contractility and reverse remodeling in cardiomyopathic UM-X7.1 hamsters with congestive heart failure. AB - OBJECTIVE: To assess the effect of short-term treatment with GH on left ventricular contractility and remodeling, after the development of heart failure in cardiomyopathic hamsters (CMH). DESIGN: Two groups of 200-day-old UM-X7.1 CMH received daily subcutaneous injections of recombinant bovine (rb) GH (1mg/kg/day) or 0.9% NaCl for 40 days. Golden Syrian hamsters (GSH) were used as controls. At 240-day-old, the hamsters were randomly subjected to (i) assessment of left ventricular systolic function in a Langendorff perfused mode followed by the determination of the passive diastolic pressure-volume relationship and morphometric measurements; (ii) assessment of left ventricular mRNA expression of genes belonging to the fetal gene program including atrial (ANP) and brain (BNP) natriuretic peptides and cardiac myosin heavy chain isoforms and of the circulating levels of the natriuretic peptides. RESULTS: Hearts from CMH were hypertrophied and dilated (p<0.05) compared to hearts from GSH, along with a approximately 10-fold increase in the circulating ANP and BNP levels. Left ventricular BNP and ANP mRNAs were elevated by 2- and 3-fold, respectively, compared to GSH. rbGH reduced both ANP mRNA and ANP circulating levels by 34% (p<0.01) but did not significantly modulate BNP levels. This effect was associated with a preserved systolic function and reverse remodeling as assessed by a leftward shift of the passive diastolic pressure-volume relationship indicating reduced ventricular dilatation. CONCLUSIONS: The data show that a short-term administration of GH in the terminal phase of the disease confers cardioprotection by attenuating systolic dysfunction and by inducing beneficial reverse remodeling. PMID- 17280862 TI - Detection of tremor bursts by a running second order moment function and analysis using interburst histograms. AB - INTRODUCTION: Conventional linear signal processing techniques are not always suitable for the detection of tremor bursts in clinical practice due to inevitable noise from electromyographic (EMG) bursts. This study introduces (1) a non-linear analysis technique based on a running second order moment function (SOMF) and (2) auto- and cross-interburst interval histograms (IBIH) showing distributions of interburst interval EMG bursts of pathological tremors illustrating an application of the SOMF. MATERIALS AND METHODS: EMG recordings from extensors and flexors of two patients with Parkinson's disease with a rest tremor and from a healthy subject during sustained muscular contraction were preliminary analyzed in a pilot study. The SOMF was obtained by repeated second order moment calculations within a window of fixed width W (time scale parameter) plotted as a function of time. Minimum SOMF values indicate local "moments of inertia" of each EMG burst. Bursts were detected and located when minimum SOMF values were below level L (decision parameter). Optimal settings of parameters W and L were calculated empirically for pathological tremor EMGs. Auto- and cross IBIHs were obtained from minimum SOMF values of detected bursts. RESULTS: Tremor frequency and phase relation between EMG bursts from auto- and cross-IBIHs agreed with those derived from spectral analysis. Burst detection by SOMF has a high sensitivity and selectivity even with noisy background. CONCLUSION: The SOMF is appropriate for detection of individual EMG bursts of pathological tremors. The technique is sensitive to non-stationary changes of tremor bursts regardless of their amplitude. IBIHs provide a measure of tremor frequency and phase difference between EMG bursts. PMID- 17280861 TI - Primary pigmented nodular adrenocortical disease reveals insulin-like growth factor binding protein-2 regulation by protein kinase A. AB - OBJECTIVE: Primary pigmented nodular adrenocortical disease (PPNAD) can occur as an isolated trait or part of Carney complex, a familial lentiginosis-multiple endocrine neoplasia syndrome frequently caused by mutations in PRKAR1A, which encodes the 1alpha regulatory subunit of protein kinase A (PKA). Because alterations in the insulin-like growth factor (IGF) axis, particularly IGF-II and IGF binding protein (IGFBP)-2 overexpression, have been implicated in sporadic adrenocortical tumors, we sought to examine the IGF axis in PPNAD. DESIGN: RNA samples and paraffin-embedded sections were procured from adrenalectomy specimens of patients with PPNAD. Changes in expression of IGF axis components were evaluated by real-time quantitative RT-PCR and immunohistochemistry. NCI-H295R cells were used to study PKA and IGF axis signaling in adrenocortical cells in vitro. RESULTS: IGFBP-2 mRNA level distinguished between the two genetic subtypes of this disease; increased IGFBP-2 expression in PRKAR1A mutation-positive PPNAD tissues was also confirmed by immunohistochemistry. Moreover, PKA inhibitors increased IGFBP-2 expression in NCI-H295R adrenocortical cells, and anti-IGFBP-2 antibody reduced their proliferation. CONCLUSIONS: IGFBP-2 expression is increased in PPNAD caused by PRKAR1A mutations, and in adrenocortical cancer cells. This is the first evidence for PKA-dependent regulation of IGFBP-2 expression in adrenocortical cells. PMID- 17280863 TI - All about FACE--plants in a high-[CO2] world. PMID- 17280864 TI - Removal of local and biased global maxima in intensity-based registration. AB - Intensity based registration (e.g., mutual information) suffers from a scalloping artifact giving rise to local maxima and sometimes a biased global maximum in a similarity objective function. Here, we demonstrate that scalloping is principally due to the noise reduction filtering that occurs when image samples are interpolated. Typically at a much smaller scale (100 times less in our test cases), there are also fluctuations in the similarity objective function due to interpolation of the signal and to sampling of a continuous, band-limited image signal. Focusing on the larger problem from noise, we show that this phenomenon can even bias global maxima, giving inaccurate registrations. This phenomenon is readily seen when one registers an image onto itself with different noise realizations but is absent when the same noise realization is present in both images. For linear interpolation, local maxima and global bias are removed if one filters the interpolated image using a new constant variance filter for linear interpolation (cv-lin filter), which equalizes the variance across the interpolated image. We use 2D synthetic and MR images and characterize the effect of cv-lin on similarity objective functions. With a reduction of local and biased maxima, image registration becomes more robust and accurate. An efficient implementation adds insignificant computation time per iteration, and because optimization proceeds more smoothly, sometimes fewer iterations are needed. PMID- 17280865 TI - Reslicing axially sampled 3D shapes using elliptic Fourier descriptors. AB - We propose a new method that interpolates between parallel slices from a 3D shape for the purposes of reslicing and putting into correspondence organ shapes acquired from volumetric medical imagery. By interpolating the coefficients of elliptic Fourier descriptors for a set of parallel contours, a new set of slices can be directly generated at desired axial locations. Neither an explicit correspondence between points on adjacent contours nor a 3D interpolating surface needs to be obtained. We apply the proposed reslicing method to experimental datasets of both synthetic 3D shapes and real prostate contours, and demonstrate that it performs as well as a common method based on variational implicit surfaces, for a much lower computational cost. We also show that reslicing and putting into correspondence an ensemble of axially sampled 3D organs enables the construction of shape models for accurate 3D segmentation. PMID- 17280866 TI - Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR. AB - BACKGROUND: Progressive outer retinal necrosis (PORN) is an ocular disease in individuals with AIDS and is associated with substantial morbidity. The optimal management of PORN and its clinical course in the HAART era is unclear. OBJECTIVE: We report a case of successfully managed PORN that provides insight into the monitoring and treatment of this disease. STUDY DESIGN: Intravitreal injections and intravenous therapy targeted towards varicella zoster virus (VZV) were used to treat PORN. HAART was initiated for HIV-1 therapy. Serial PCR for VZV was performed on aqueous humor to monitor the clinical course. RESULTS: The presence of VZV DNA from aqueous humor correlated with clinical exacerbations of disease. Initiation of twice weekly intravitreal injections with dual antiviral drugs appeared to be an important therapeutic intervention that resulted in remission of PORN. Secondary prophylaxis against VZV was successfully withdrawn after HAART induced partial immune recovery. CONCLUSION: In addition to aggressive therapy with intravitreal injections, HAART and quantitative measurements of VZV DNA from aqueous humor have important roles in the management of PORN. A multidisciplinary approach involving specialists in infectious diseases, ophthalmology, and clinical microbiology will improve the chances for successful long-term outcomes. PMID- 17280867 TI - Differential effects of Chlamydia pneumoniae infection on cytokine levels in human T lymphocyte- and monocyte-derived cell cultures. AB - Continuous cultures of human lymphocyte- and monocyte-derived cell lines were examined for levels of immunoregulatory cytokines important in resistance to the intracellular opportunistic bacterium Chlamydia pneumoniae (Cp), a ubiquitous pathogen widely disseminated in the population and hypothesized to be involved in chronic inflammatory diseases such as atherosclerosis and neurological diseases like multiple sclerosis and Alzheimer's disease. The results of this study showed that the continuous human T lymphocyte cell line MOLT-4 and the continuous monocytic cell line THP-1 were readily infected by Cp in vitro as shown by immunofluorescence microscopy for Cp lipopolysaccharide (LPS). The 16S rRNA expression determined by real-time RT-PCR increased rapidly after infection of either cell line with these bacteria. The THP-1 cells infected with Cp showed increased levels of the immunoregulatory cytokine IL-12 and also of TNFalpha and IL-10 compared to cultures stimulated with heat-killed Cp (KCp) or Escherichia coli LPS as a control. Stimulation of MOLT-4 cells with KCp or E. coli LPS also induced the Th1 cytokines IFNgamma and IL-12 and the Th2 cytokine IL-10, but infection with viable Cp induced higher Th1 cytokine levels. These results suggest that Cp infection induces a predominant Th1 cytokine profile by T cells, in addition to induction of TNFalpha by monocytes/macrophages. Such effects are likely involved in antibacterial immunity against Cp infection. PMID- 17280868 TI - Characterization of four novel genomic regions of uropathogenic Escherichia coli highly associated with the extraintestinal virulent phenotype: a jigsaw puzzle of genetic modules. AB - Extraintestinal pathogenic Escherichia coli (ExPEC) are a major cause of urinary tract infections, sepsis, and neonatal meningitis. A variety of virulence factors in these strains is encoded by mobile genetic elements, such as transposons or pathogenicity islands (PAIs). Using subtractive cloning of ExPEC genomes, we recently detected short DNA fragments, which were significantly associated with the extraintestinal virulent phenotype. In this study, we identified four novel genomic DNA regions of the highly virulent uropathogenic E. coli strain JS299 carrying these previously identified DNA fragments. Characterization of the partial sequences of the genomic DNA regions revealed complex DNA arrangements with variable genetic compositions regarding the G+C contents and codon usage patterns. The prevalence of 15 previously uncharacterized genes was determined in a collection of clinical ExPECs and commensal E. coli strains by means of DNA microarray analyses. From this, 13 novel DNA sequences were demonstrated to be significantly associated with extraintestinal virulent strains, and thus may represent new virulence traits. Beside genes predicted to play a role in metabolic functions, such as sucrose utilization (scr), we identified DNA sequences shared by both ExPEC and enteropathogenic E. coli (EPEC). These sequences were significantly more prevalent among ExPECs when compared to commensal E. coli isolates. Our results support the idea of a considerable genetic variability among ExPEC strains and suggest that the novel genomic determinants described in this study may contribute to the ExPEC virulence. PMID- 17280869 TI - Sphingosine-1-phosphate signaling in the cardiovascular system. AB - Increasing evidence suggests a key role for the bioactive lipid sphingosine-1 phosphate (S1P) and its G-protein-coupled receptors (S1P(1-5)) in the cardiovascular system. Recent advances in sphingolipid research indicates that cardiomyocyte, vascular smooth muscle and endothelial cell function is greatly influenced by the relative expression and activity both of S1P receptors and of the enzymes involved in sphingolipid metabolism. For instance, the discovery and development of S1P receptor agonists such as FTY720 has clearly indicated the involvement of S1P receptors in the regulation of heart rate. In addition, sphingolipid metabolism induced, for example, by tumour necrosis factor-alpha or angiotensin II plays an important role in vessel structure, function and tone. PMID- 17280870 TI - Evolutionary paradigm of chloroquine-resistant malaria in India. AB - Drug pressure in the field is believed to be responsible for the emergence of drug-resistant Plasmodium falciparum, the parasite that causes malaria. Variants of the P. falciparum chloroquine resistance transporter (pfcrt) gene have been shown to be responsible for conferring resistance to the commonly used drug chloroquine. In particular, an amino acid mutation, K76T, was shown to have a strong positive correlation with the chloroquine-resistant varieties of malaria parasites. Global studies have reported highly reduced genetic diversity surrounding K76T in the pfcrt gene, which indicates that the mutation has been a target of positive Darwinian natural selection. However, two recent studies of P. falciparum in India found high genetic diversity in the pfcrt gene, which, at first sight, do not support the role of natural selection in the evolution of chloroquine resistance in India. PMID- 17280871 TI - Expression of Plxdc2/TEM7R in the developing nervous system of the mouse. AB - Plexin-domain containing 2 (Plxdc2) is a relatively uncharacterised transmembrane protein with an area of nidogen homology and a plexin repeat (PSI domain) in its extracellular region. Here, we describe Plxdc2 expression in the embryonic mouse, with particular emphasis on the developing central nervous system. Using light microscopy and optical projection tomography (OPT), we analyse RNA in situ hybridization patterns and expression of two reporter genes, beta-geo (a fusion of beta-galactosidase to neomycin phosphotransferase) and placental alkaline phosphatase (PLAP) in a Plxdc2 gene trap mouse line (KST37; [Leighton, P.A., Mitchell, K.J., Goodrich, L.V., Lu, X., Pinson, K., Scherz, P., Skarnes, W.C., Tessier-Lavigne, M., 2001. Defining brain wiring patterns and mechanisms through gene trapping in mice. Nature 410, 174-179]). At mid-embryonic stages (E9.5 E11.5) Plxdc2-betageo expression is prominent in a number of patterning centres of the brain, including the cortical hem, midbrain-hindbrain boundary and the midbrain floorplate. Plxdc2 is expressed in other tissues, most notably the limbs, lung buds and developing heart, as well as the spinal cord and dorsal root ganglia. At E15.5, expression is apparent in a large number of discrete nuclei and structures throughout the brain, including the glial wedge and derivatives of the cortical hem. Plxdc2-betageo expression is particularly strong in the developing Purkinje cell layer, especially in the posterior half of the cerebellum. The PLAP marker is expressed in a number of axonal tracts, including the posterior commissure, mammillotegmental tract and cerebellar peduncle. We compare Plxdc2-betageo expression in the embryonic brain with the much more restricted expression of the related gene Plxdc1 and with members of the Wnt family (Wnt3a, Wnt5a and Wnt8b) that show a striking overlap with Plxdc2 expression in certain areas. PMID- 17280872 TI - Developmental regulation of rat Ubc13 and Uev1B genes in the nervous system. AB - Ubiquitin is a highly conserved protein in eukaryotes, and regulates diverse cellular processes. Lys-63-linked poly-ubiquitination has been recently identified to be involved in non-proteolytic processes such as DNA repair and cytokine-mediated signal transduction. Although, the heterodimeric enzymes Ubc13 and Uev are required for ubiquitination, their expressional regulation is not known. We have analyzed changes in their expression during brain development. Northern blot analysis revealed that the expression levels of the two genes were very similar. Expression of both genes decreased gradually during the embryonic stages, then increased in the late postnatal period and was moderate in the adult. In situ hybridization analyses revealed that the expression patterns of the two genes were similar. Expression was observed in various regions in the embryonic brain but became restricted to specific regions after birth. In the adult, their expression was similar in regions such as the cerebral cortex, hippocampus, and substantia nigra, but different in the cerebellum. These results suggest that Ubc13 may be closely associated with Uev1B. PMID- 17280873 TI - Detection of mosaic pattern of mitochondrial DNA alterations in different populations of cells from the same endometrial tumor. AB - Somatic mitochondrial DNA (mtDNA) alterations including point mutations and microsatellite instability (MSI) have been frequently detected in human cancers. To further explore the extensiveness of mtDNA alterations, we have analyzed the occurrence of somatic mtDNA mutations in different populations of endometrial cancer cells from the same tumor tissues as compared with adjacent non-tumor cells. Laser-captured micro-dissection was used to harvest endometrial cancer cells from separated areas of the same tumor and adjacent normal cells. Total DNA isolated from micro-dissected cells was PCR amplified and analyzed for mtDNA alterations by polyacrylamide gel electrophoresis and DNA sequencing. Multiple mtDNA alterations were detected in different portions of the same tumor. Different populations of endometrial cancer cells carried different patterns of mtDNA mutations. Interestingly, unlike previous reports, most mutations were found to be heteroplasmic. We have demonstrated the occurrence of hyper variability of mtDNA alterations in a single piece of tumor tissue. Our observations support the hypothesis that the accumulation of mtDNA alterations is random and expands independently. The data presented here showed the heterogeneity of cancer cells in terms of mtDNA alterations in endometrial cancer. PMID- 17280874 TI - Depletion of mtDNA: syndromes and genes. AB - Maintenance of mitochondrial DNA (mtDNA) requires the concerted activity of several nuclear-encoded factors that participate in its replication, being part of the mitochondrial replisome or ensuring the balanced supply of dNTPs to mitochondria. In the past decade, a growing number of syndromes associated with dysfunction due to tissue-specific depletion of mtDNA (MDS) have been reported. This article reviews the current knowledge of the genes responsible for these disorders, the impact of different mutations in the epidemiology of MDS and their role in the pathogenic mechanisms underlying the different clinical presentations. PMID- 17280875 TI - Evaluation of respiratory chain failure in mitochondrial cardiomyopathy by assessments of 99mTc-MIBI washout and 123I-BMIPP/99mTc-MIBI mismatch. AB - Cardiomyopathy is one of the main features that determines prognosis in patients with mitochondrial encephalomyopathy. We investigated respiratory chain failure using 99mTc-MIBI- and 123I-BMIPP-SPECT in vivo in five patients with mitochondrial cardiomyopathty. With the lowering of cardiac function, the 99mTc MIBI-washout rate (WOR) increased, and the 99mTc-MIBI-uptake decreased, conversely. In patients who showed severe cardiac involvement, 99mTc-MIBI-uptake was markedly reduced, and by contrast, 123I-BMIPP-uptake increased (123I BMIPP/99mTc-MIBI mismatch). There were significant correlations between the WOR on 99mTc-MIBI-SPECT and interventricular septal thickness (IVST) on echocardiography and between WOR and left ventricular ejection fraction (LVEF) on 99mTc-MIBI-SPECT. The increased WOR and decreased uptake of 99mTc-MIBI were reflected by the lowered mitochondrial membrane potential created by mitochondrial respiratory chain whereas 123I-BMIPP/99mTc-MIBI mismatch may be created by the enhanced triglyceride-pool. These nuclear medicine techniques are the potential tools to evaluate the energy state in mitochondrial cardiomyopathy. PMID- 17280876 TI - Heteroplasmic mutation of mitochondrial DNA D-loop and 4977-bp deletion in human cancer cells during mitochondrial DNA depletion. AB - Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various human cancers. Many cancers have high frequently of mtDNA with homoplasmic point mutations, and carry less frequently of mtDNA with large-scale deletions as compared with corresponding non-cancerous tissue. Moreover, most cancers harbor a decreased copy number of mtDNA than their corresponding non-cancerous tissue. However, it is unclear whether the process of decreasing in mtDNA content would be involved in an increase in the heteroplasmic level of somatic mtDNA point mutation, and/or involved in a decrease in the proportion of mtDNA with large scale deletion in cancer cells. In this study, we provided evidence that the heteroplasmic levels of variations in cytidine number in np 303-309 poly C tract of mtDNA in three colon cancer cells were not changed during an ethidium bromide induced mtDNA depleting process. In the mtDNA depleting process, the proportions of mtDNA with 4977-bp deletion in cybrid cells were not significantly altered. These results suggest that the decreasing process of mtDNA copy number per se may neither contribute to the shift of homoplasmic/heteroplasmic state of point mutation in mtDNA nor to the decrease in proportion of mtDNA with large-scale deletions in cancer cells. Mitochondrial genome instability and reduced mtDNA copy number may independently occur in human cancer. PMID- 17280877 TI - DNA recombination protein-dependent mechanism of homoplasmy and its proposed functions. AB - Homoplasmy is a basic genetic state of mitochondria, in which all of the hundreds to thousands of mitochondrial (mt)DNA copies within a cell or an individual have the same nucleotide-sequence. It was recently found that "vegetative segregation" to generate homoplasmic cells is an active process under genetic control. In the yeast Saccharomyces cerevisiae, the Mhr1 protein which catalyzes a key reaction in mtDNA homologous recombination, plays a pivotal role in vegetative segregation. Conversely, within the nuclear genome, homologous DNA recombination causes genetic diversity. Considering these contradictory roles of this key reaction in DNA recombination, possible functions of homoplasmy are discussed. PMID- 17280878 TI - Analysis of disease-associated ND4 mutations: how do we know which mutation is pathogenic? AB - It is not uncommon to identify more than one mtDNA replacement mutations in the specimens from patients. However, we usually do not know if the identified mtDNA mutation is pathogenic or not. Even functional assays are available to use, we would not know which mutation(s) is to be tested. To provide a rapid method for initial evaluation for the pathogenicity of the replacement mutation, we compared three evolutional analyses: primate conservation index (PCI), mammalian conservation index (MCI), and conservation index across a wide spectrum of species (CI). After analyzing 35 so-called diseases-associated replacement mutations of ND4, we found 8 pathogenic mutations, 15 nonpathogenic mutations, and 12 mutations of undetermined significance. The MCI classification appears to be the best one among the three systems. This study demonstrates that evolutional analysis can serve as a rapid evaluation for the pathogenicity of mtDNA replacement mutations. PMID- 17280879 TI - Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. AB - A growing body of evidence suggests that mammalian mitochondrial DNA takes on higher structure called nucleoid or mitochromosome corresponding to that of nuclear DNA. Mitochondrial transcription factor A (TFAM), which was cloned as a transcription factor for mitochondrial DNA, has known to be essential for the maintenance of mitochondrial DNA. Human TFAM has an ability to bind to DNA in a sequence-independent manner and is abundant enough to cover whole region of mitochondrial DNA, owing to which TFAM stabilizes mitochondrial DNA through formation of nucleoid and regulates (or titrates) the amount of mitochondrial DNA. Overexpression of human TFAM in mice increases the amount of mitochondrial DNA and dramatically ameliorates the cardiac dysfunctions caused by myocardial infarction. The maintenance of integrity of mitochondrial DNA is important for keeping proper cellular functions both under physiological and pathological conditions. TFAM may play a crucial role in maintaining mitochondrial DNA as a main component of the nucleoid. PMID- 17280880 TI - Accumulation of 8-oxo-deoxyguanosine in cardiovascular tissues with the development of hypertension. AB - Accumulation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in DNA is associated with mutagenesis and cell death. Little attention has been given to the biological significance of 8-oxo-dG accumulation in cardiovascular tissues during the different stage of hypertension and its prevention. We thus investigated the levels and localization of both 8-oxo-dG accumulation and expression of MTH1, which hydrolyzes 8-oxo-dGTP to prevent its incorporation into DNA, in the thoracic aorta prepared from stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wister-Kyoto rats (WKY), aged 5-32 weeks. HPLC-MS/MS analysis revealed that the levels of nuclear 8-oxo-dG in the aorta increased significantly in SHRSP, but not WKY, with aging. Immunohistochemical study revealed that both TUNEL reactivity and 8-oxo-dG immunoreactivity were increased in smooth muscle cells (SMC) and endothelial cells (EC) of the aorta with aging, and they exhibited similar distributions in serial sections. The number of 8-oxo dG and TUNEL positive cells in EC, but not in SMC, was significantly higher in SHRSP than WKY at 32 weeks of age. In contrast, the expression levels of Mth1mRNA and MTH1 protein in the aorta were similarly decreased both in SHRSP and WKY with aging. However, the number of MTH1 expressing EC was remarkably increased in the older SHRSP compared to the younger ones or age-matched WKY. Hypertension significantly increased not only 8-oxo-dG accumulation but also the expression of MTH1 in EC of the aorta during aging. While accumulation of 8-oxo-dG in SMC of the aorta was slightly increased, the expression of MTH1 protein in SMC was rather decreased by hypertension. We thus suggest that MTH1 may protect EC in the aorta from the oxidative damage increased by hypertension. PMID- 17280882 TI - Monitoring the reaction of hemoglobin with hydrogen peroxide by capillary electrophoresis-chemiluminescence detection. AB - The reaction of hemoglobin (Hb) with hydrogen peroxide (H2O2) leads to fluorescent product and heme degradation. We applied capillary electrophoresis chemiluminescence (CE-CL) detection to monitor the course of Hb reacting with H2O2. Hb and released free iron ion (Fe3+) were detected based on their enhancement effects on CL of the luminol-H2O2 system. In this study, we discovered an intermediate of this reaction which intensely enhances the luminol H2O2 CL system. The ratio of max CL signals of Fe3+, Hb and this intermediate is circa 1:10:60. PMID- 17280881 TI - Simultaneous determination of a selective adenosine 2A agonist, BMS-068645, and its acid metabolite in human plasma by liquid chromatography-tandem mass spectrometry--evaluation of the esterase inhibitor, diisopropyl fluorophosphate, in the stabilization of a labile ester-containing drug. AB - BMS-068645 is a selective adenosine 2A agonist that contains a methyl ester group which undergoes esterase hydrolysis to its acid metabolite. To permit accurate determinations of circulating BMS-068645 and its acid metabolite, blood samples must be rapidly stabilized at the time of collection. A sensitive, rapid and specific liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous quantitation of BMS-068645 and its acid metabolite in human plasma has been developed and validated using diisopropyl fluorophosphate (DFP) as the esterase inhibitor to prevent BMS-068645 from converting to its acid metabolite. The D(5)-stable isotope labeled analogs of BMS-068645 and its metabolite were used as the internal standards (IS). Analytes and IS in plasma containing 20 mM DFP were acidified and extracted into methyl tert-butyl ether. The liquid-liquid extraction effectively eliminated the strong matrix effect caused by the esterase inhibitor. The chromatographic separation was achieved on a Waters Atlantis C18 column with a run time of 4 min. Detection was performed on a Sciex API 4000 with positive ion electrospray mode (ESI/MS/MS), monitoring the ion transitions m/z 487>314 and 473>300 for BMS-068645 and its acid metabolite, respectively. The method was validated over the range from 0.020 to 10.0 ng/mL for BMS-068645 and 0.050 to 10.0 ng/mL for its acid metabolite. Inter- and intra-run precision for the quality control samples during validation were less than 8.7% and 4.0%, respectively, for the two analytes. The assay accuracy was within +/-5.4% of the nominal values. The esterase inhibitor effectively stabilized BMS-068645 during blood collection and storage. Blood collection tubes containing DFP were easily prepared and used at the clinical sites and could be stored at -30 degrees C for 3 months. This method demonstrated adequate sensitivity, specificity, accuracy, precision, stability and ruggedness to support the analysis of human plasma samples in pharmacokinetic studies. PMID- 17280884 TI - Nonsurgical management of soft tissue deficiencies for anterior single implant supported restorations: a clinical report. AB - Periodontal surgical procedures may not always offer a predictable level of success in the reproduction of a natural gingival architecture. Two different nonsurgical approaches are described for the management of soft tissue deficiencies in anterior implant-supported restorations. Clinically acceptable esthetic outcomes of anterior implant restorations can be achieved by using zirconium custom abutments and gingiva-colored dental porcelain. PMID- 17280885 TI - Dose-related effects of epinephrine on human gingival blood flow and crevicular fluid production used as a soaking solution for chemo-mechanical tissue retraction. AB - STATEMENT OF PROBLEM: Epinephrine is a frequently used agent for impregnation of the retraction cord. Removal of retraction cord from the gingival sulcus has been shown to elicit a hyperemic response that could be prevented by epinephrine. However, the epinephrine may cause local or systemic adverse effects in the circulation. PURPOSE: The aim of this study was to identify the effective concentration of epinephrine that may prevent the hyperemic response and consequently keep the crevicular fluid production low after cord removal without local or systemic side effects. MATERIAL AND METHODS: Seventeen healthy human subjects had their crevicular fluid volume and gingival blood flow measured by Periotron and laser Doppler flowmetry, respectively, before and after cord removal at the left maxillary central incisor. The right maxillary incisor served as the control. Retraction cords were presoaked in physiological saline or various concentrations (0.001%, 0.01%, and 0.1% w/v) of epinephrine solution. Double repeated-measures analysis of variance with the Fisher Least Significant Difference post hoc test was used to statistically evaluate the blood flow values (mean +/- SE, alpha=.05), and the Wilcoxon matched pair test was used for crevicular fluid values, given as median (25-75 percentile, alpha=.01). RESULTS: In the saline group, cord removal resulted in elevated blood flow (140% +/- 11%, P<.001) and crevicular fluid production (300% (130%-470%), P<.05). After cord removal in the 0.01% and 0.1% epinephrine groups, blood flow remained low for the measured period (43%-70%, P<.05). The crevicular fluid production transiently increased in the 0.01% epinephrine group (170% (140%-380%), P<.001), but then returned to baseline level and remained low as for the 0.1% group. No systemic vascular effect was detected in any groups. CONCLUSION: The prolonged increase in crevicular fluid production and hyperemic response after cord removal can be prevented by application of 0.01% epinephrine solution without systematic changes. PMID- 17280886 TI - Assessment of preference of mixing techniques and duration of mixing and tray loading for two viscosities of vinyl polysiloxane material. AB - STATEMENT OF PROBLEM: Information regarding operators' preferences for different impression mixing techniques and duration of mixing and tray loading is limited. PURPOSE: The purpose of this study was to assess operators' preferences, and the duration of mixing and tray loading using different mixing techniques. MATERIAL AND METHODS: Thirty dentists, 30 dental assistants, and 30 inexperienced dental students evaluated mixing heavy-body vinyl polysiloxane material (VPS) using electronic mixing compared to automixing, and extra-heavy-body material using electronic mixing compared to hand mixing. Participants rated their level of preference using a scale from 0 to 10 for ease of mixing, control of loading, quality of mixing, level of cleanliness, and overall rating. The duration of mixing and tray loading was also measured. Mean values were compared within participant groups using the paired t test (alpha=.05) and between groups using 1 way analysis of variance (ANOVA) (alpha=.05). Holm's procedure was used to adjust the level of significance for the multiple comparisons. RESULTS: The paired t test showed that mean values of level of preference for electronic mixing were significantly higher (P<.001 to .033) than those for automixing or hand mixing. The mean values of duration of mixing and tray loading with electronic mixing were significantly higher (P<.001 to .002) than those with automixing or hand mixing, except for students using heavy-body materials (P=.31). One-way ANOVA showed that there were no significant differences between the 3 participant groups in preference and duration of mixing and tray loading, both of heavy-body and extra-heavy-body VPS impression materials. CONCLUSIONS: All participant groups preferred electronic mixing to automixing or hand mixing. Electronic mixing was significantly slower for all groups except for students using heavy body materials. There was no significant difference between the 3 participant groups in the preference or duration of mixing and tray loading for the mixing techniques tested. PMID- 17280887 TI - Influence of bond quality on failure load of leucite- and lithia disilicate-based ceramics. AB - STATEMENT OF PROBLEM: The long-term survival of bonded ceramic restorations for posterior teeth is a clinical concern. The durability of the bond between the ceramic and dentin during clinical service is a factor in the load-bearing capacity of the restoration. PURPOSE: This study aimed to evaluate the effect of interfacial bonding quality on the interface failure initiation loads of 2 all ceramic systems. MATERIAL AND METHODS: One leucite-reinforced ceramic, IPS Empress (E1), and 1 lithia disilicate glass-ceramic, IPS Empress 2 (E2), were used to form disks 8.5 mm in diameter, with an approximate 1.35-mm total thickness (n=45). The ceramic specimens were fabricated in a manner that simulated their clinical application. The E1 specimens were fabricated using the staining technique, and the E2 specimens were made using a layering technique. Completed disks of each ceramic system were divided into 3 subgroups (n=15) that were subsequently cemented using 1 of 3 bonding conditions (Control, Cer, Sub). The control group followed ideal bonding protocol, whereas groups Cer and Sub had bonds that were compromised between the cement and the ceramic (Cer) or the substrate and the cement (Sub). All luted specimens were loaded at the center with a 10-mm-diameter ball indenter at a crosshead speed of 0.01 mm/min in a universal testing machine. Intermittent loads were applied in increasing increments of 50 N until a fracture could be observed in the ceramic substrate by transillumination with x2.6 optical magnification. The maximum load applied prior to crack observation was recorded as the failure initiation load. Survival analytical methods were used to determine differences between groups. RESULTS: The characteristic fracture initiation loads ranged from 223.5 to 760.6 N. Group E2 had the greatest mean observed load to failure (715.6 N), which was significantly greater than group E1 (P<.001). For both the E1 and E2 ceramic systems, the control groups had significantly greater mean fracture initiation loads than either of the interface-inhibited Cer and Sub groups. CONCLUSIONS: Poor bond quality at either the ceramic-cement or dentin-cement interface can significantly reduce the fracture initiation load-bearing capacity of ceramic disks bonded to compliant dentin-like substrates. For the E2 ceramic material, disruption of the ceramic-cement interface had a more detrimental effect on the load-bearing capacity of the simulated restoration than the disruption of the cement-dentin interface. PMID- 17280888 TI - The effect of ceramic thickness and number of firings on the color of ceramic systems: an in vitro study. AB - STATEMENT OF PROBLEM: Although all-ceramic restorations are widely used, there is a lack of information on how color is affected by fabrication procedures. Color matching problems may be encountered in a definitive restoration despite careful shade selection. PURPOSE: The aim of this study was to evaluate the effect of dentin ceramic thickness and repeated firings on the color of glass-infiltrated aluminum-oxide (In-Ceram) and leucite-reinforced (IPS Empress) all-ceramic systems using a colorimeter. MATERIAL AND METHODS: Twenty-one disc-shaped specimens, 10 mm in diameter with a 0.6-mm core thickness and 0.5-, 1-, or 1.5-mm dentin ceramic thickness, were made from each of 2 ceramic systems (n=7) . Repeated firings were performed for each group, and the color differences were compared with the color after the initial firing. Color differences among ceramic specimens were measured using a colorimeter (XL-20 Colorimeter), and data were expressed in Commission Internationale d'Eclairage (CIE) LAB system coordinates. Repeated-measures analysis of variance was used to analyze the data (number of firings, ceramic brand, and ceramic thickness) for significant differences. The Tukey honestly significant difference test and paired 2-tailed tests were used to perform multiple comparisons (alpha=.05). RESULTS: The L( *)a( *)b( *) values of ceramic systems were affected by the number of firings (3, 5, or 7) (P<.01) and ceramic brand (In-ceram or IPS Empress) (P<.01). L( *) and a( *) values were affected by ceramic thickness (0.5, 1, or 1.5 mm) (P<.01); however, b( *) value was not affected by ceramic thickness (P=.075). Significant interactions were present in L( *), a( *), b( *) values between number of firings and ceramic brand (P<.01), and between ceramic brand and ceramic thickness (P<.05). Significant interactions were present between number of firings and ceramic thickness (P<.01) in L( *) and b( *) values but not in the a( *) value (P=.379). CONCLUSION: The analysis revealed that there were substantial changes in L( *)a( *)b( *) color data as the number of firings increased, which resulted in perceptual color changes in L( *)a( *)b( *) color parameters. PMID- 17280889 TI - Removable acrylic resin disk as a sampling system for the study of denture biofilms in vivo. AB - STATEMENT OF PROBLEM: The adhesion of microorganisms to a denture surface can result in denture stomatitis. PURPOSE: The purpose of this study was to evaluate denture biofilm in vivo using a new sampling system to gain a better understanding of plaque organization in Candida-induced denture stomatitis. Removable acrylic resin disks were used with self-adhesive paper disks to compare biofilm formation and retention efficacy of both sampling systems. MATERIAL AND METHODS: Twenty-one subjects with a complete maxillary denture were recruited, 12 with a clinical diagnosis of chronic denture stomatitis and 9 with a clinically healthy palatal mucosa. A custom-made autopolymerized 3.0-mm-diameter acrylic resin disk inlay was inserted in a cavity prepared within the intaglio surface of the maxillary denture in contact with either normal or inflamed mucosa. Next to the acrylic resin disk, a self-adhesive paper disk was placed for comparison of the 2 sampling techniques. Denture biofilms were collected within variable time periods of 1 hour to several months, and descriptive data were provided by means of scanning electron microscopy analyses. The method of retention and recovery of specimen disks were evaluated between both sampling techniques using a chi-square test to assess significant differences (alpha=.05). RESULTS: Early event features of denture biofilms showed differences in biofilm organization between the 2 sampling techniques but became subtler with increased time periods. Regardless of the sampling technique, interparticipant variations could be observed as to rate, microorganism density, and architectural pattern. In general, denture biofilm formation was increased when the sampling disks were localized in areas affected by denture stomatitis. CONCLUSION: The new sampling technique provides reliable information with controlled formation time of denture biofilm in its natural environment. PMID- 17280890 TI - Finite element stress analysis and fatigue behavior of cast circumferential clasps. AB - STATEMENT OF PROBLEM: Deformation and fracture of cast circumferential clasps may be a result of stresses induced during mastication. Most biomechanical clasp studies have been performed only under static conditions. There is little information regarding behavior of clasps over time. PURPOSE: The purpose of this study was to evaluate stress distribution on cast circumferential clasps, and the displacements or deformations, depending on the load placement and range. Fatigue analysis was then conducted to evaluate the behavior of clasps over time. MATERIAL AND METHODS: Static stress values and distribution induced in cast circumferential clasps were calculated and studied using 3-dimensional finite element experimental models for Co-Cr cast circumferential clasps. Average loads between 20 and 35 N were applied vertically along the clasp components to simulate static stress distribution during translation and rotation of the denture. After determination of stress concentration areas, the fatigue behavior of clasps was studied using finite element analysis during simulated cyclic masticatory loads (loads between 0 and 20 N included in 4500 masticatory cycles over 24 hours). RESULTS: For the translation simulation, the maximum stress was 310.27 MPa, located near the lower margin of the retentive arm, and for the rotation simulation, the maximum stress was 310.31 MPa, located near the upper margin of the same arm. Under simulated static load, the magnitude of stresses found in the clasps was under the reported yield strength (640 MPa) of the Co-Cr alloy. The maximum stresses indicated the area of highest fracture risk, but fractures occurred only under a simulated cyclic mastication load representing 5.5 years of service. CONCLUSION: Within the limitations of the simulation study, static stress analysis of cast circumferential clasps indicated the location of greatest fracture risk to be at the junction of the clasp arm with the body, for all situations. In addition, fatigue analysis estimated clasp degradation over time and the survival rate of the same clasps, which was found to be 5.5 years, on average. PMID- 17280892 TI - The use of vacuum-formed resin sheets as spacers for putty-wash impressions. PMID- 17280891 TI - Measurement of color for craniofacial structures using a 45/0-degree optical configuration. AB - STATEMENT OF PROBLEM: The color of vital craniofacial structures has not been measured accurately. PURPOSE: The purpose of this study was to determine the color of vital craniofacial structures and evaluate the validity and test-retest reliability of a noncontacting 45/0-degree optical configuration. MATERIAL AND METHODS: A spectroradiometer and an external light source were configured in a noncontacting 45/0-degree (45-degree illumination and 0-degree observer) optical configuration to measure the color of subjects' vital craniofacial structures (central and lateral incisor and canine, attached gingiva, lips, and facial skin). The 120 subjects were stratified into 5 age groups with 4 racial categories and balanced for gender. For evaluation of validity, linear regressions and 95% confidence intervals were calculated for DeltaL( *), Deltaa( *), Deltab( *) [color difference of (CIE) LAB values] between the measured and certified values of the 22 color patches of the DC Color Checker. For test-retest reliability, a random sample of 12 (10%) subjects was remeasured at a second visit. Paired t tests, correlations, and Bland-Altman analyses were performed between the first and second measurements of the 12 pairs of L( *), a( *), and b( *) values for the 6 craniofacial structures. RESULTS: For validity, the mean color difference and linear regression for Commission Internationale d'Eclairage (CIE) LAB values between measured and certified color of the 22 opaque color patches were DeltaE of 1.46 and 0.99 for all regressions, respectively. Only Deltaa( *) did not contain zero in its 95% confidence interval. For test-retest reliability, no paired t tests were significantly different from each other, and the Pearson correlation coefficient ranged from 0.9 (9 pairs) to 0.7 (3 pairs). Ten of the 18 Bland-Altman plots showed good reliability. CONCLUSION: The spectral reflectance of craniofacial structures can be measured with acceptable validity and test-retest reliability using a noncontacting 45/0-degree optical configuration. PMID- 17280893 TI - Masking technique of cast for diagnostic waxing of labial veneers. PMID- 17280894 TI - Role of CCN2/CTGF/Hcs24 in bone growth. AB - Our bones mostly develop through a process called endochondral ossification. This process is initiated in the cartilage prototype of each bone and continues through embryonic and postnatal development until the end of skeletal growth. Therefore, the central regulator of endochondral ossification is the director of body construction, which is, in other words, the determinant of skeletal size and shape. We suggest that CCN2/CTGF/Hcs24 (CCN2) is a molecule that conducts all of the procedures of endochondral ossification. CCN2, a member of the CCN family of novel modulator proteins, displays multiple functions by manipulating the local information network, using its conserved modules as an interface with a variety of other biomolecules. Under a precisely designed four-dimensional genetic program, CCN2 is produced from a limited population of chondrocytes and acts on all of the mesenchymal cells inside the bone callus to promote the integrated growth of the bone. Furthermore, the utility of CCN2 as regenerative therapeutics against connective tissue disorders, such as bone and cartilage defects and osteoarthritis, has been suggested. Over the years, the pathological action of CCN2 has been suggested. Nevertheless, it can also be regarded as another aspect of the physiological and regenerative function of CCN2, which is discussed as well. PMID- 17280895 TI - Action potential in charophytes. AB - The plant action potential (AP) has been studied for more than half a century. The experimental system was provided mainly by the large charophyte cells, which allowed insertion of early large electrodes, manipulation of cell compartments, and inside and outside media. These early experiments were inspired by the Hodgkin and Huxley (HH) work on the squid axon and its voltage clamp techniques. Later, the patch clamping technique provided information about the ion transporters underlying the excitation transient. The initial models were also influenced by the HH picture of the animal AP. At the turn of the century, the paradigm of the charophyte AP shifted to include several chemical reactions, second messenger-activated channel, and calcium ion liberation from internal stores. Many aspects of this new model await further clarification. The role of the AP in plant movements, wound signaling, and turgor regulation is now well documented. Involvement in invasion by pathogens, chilling injury, light, and gravity sensing are under investigation. PMID- 17280896 TI - Similarity of the domain structure of proteins as a basis for the conservation of meiosis. AB - Meiosis is conserved in all eucaryotic kingdoms, and homologous rows of variability are revealed for the cytological traits of meiosis. To find the nature of these phenomenons, we reviewed the most-studied meiosis-specific proteins and studied them with the methods of bioinformatics. We found that synaptonemal complex proteins have no homology of amino-acid sequence, but are similar in the domain organization and three-dimensional (3D) structure of functionally important domains in budding yeast, nematode, Drosophila, Arabidopsis, and human. Recombination proteins of Rad51/Dmc1 family are conserved to the extent which permits them to make filamentous single-strand deoxyribonucleic acid (ssDNA)-protein intermediates of meiotic recombination. The same structural principles are valid for conservation of the ultrastructure of kinetochores, cell gap contacts, and nuclear pore complexes, such as in the cases when ultrastructure 3D parameters are important for the function. We suggest that self-assembly of protein molecules plays a significant role in building-up of all biological structures mentioned. PMID- 17280897 TI - Fibroblast differentiation in wound healing and fibrosis. AB - The contraction of granulation tissue from skin wounds was first described in the 1960s. Later it was discovered that during tissue repair, fibroblasts undergo a change in phenotype from their normal relatively quiescent state in which they are involved in slow turnover of the extracellular matrix, to a proliferative and contractile phenotype termed myofibroblasts. These cells show some of the phenotypic characteristics of smooth muscle cells and have been shown to contract in vitro. In the 1990s, a number of researchers in different fields showed that myofibroblasts are present during tissue repair or response to injury in a variety of other tissues, including the liver, kidney, and lung. During normal repair processes, the myofibroblastic cells are lost as repair resolves to form a scar. This cell loss is via apoptosis. In pathological fibroses, myofibroblasts persist in the tissue and are responsible for fibrosis via increased matrix synthesis and for contraction of the tissue. In many cases this expansion of the extracellular matrix impedes normal function of the organ. For this reason much interest has centered on the derivation of myofibroblasts and the factors that influence their differentiation, proliferation, extracellular matrix synthesis, and survival. Further understanding of how fibroblast differentiation and myofibroblast phenotype is controlled may provide valuable insights into future therapies that can control fibrosis and scarring. PMID- 17280898 TI - Tumor hypoxia and targeted gene therapy. AB - Hypoxia is an integral characteristic of the tumor microenvironment, primarily due to the microvascular defects that accompany the accelerated neoplastic growth. The presence of tumor hypoxic areas correlates with negative outcome after radiotherapy, chemotherapy, and surgery, as hypoxia not only provides an environment directly facilitating chemo- and radio-resistance, but also encourages the evolution of phenotypic changes inducing permanent resistance to treatment and metastatic spread. Therefore, successful treatment of hypoxic cells has the potential to not only improve local control but also impact overall patient survival. Specific and selective targeting of hypoxic tumor areas can be achieved at all three steps of a gene therapy treatment: delivery of the therapeutic gene to the tumor, regulation of gene expression, and therapeutic efficacy. In this review the latest developments and innovations in hypoxia targeted gene therapy are discussed. In particular, approaches such as hypoxia conditionally replicating viruses, cellular vehicles, and gene therapy means to disrupt the hypoxia-inducible factor (HIF) signaling are outlined. PMID- 17280899 TI - Cellular basis of chronic obstructive pulmonary disease in horses. AB - Chronic obstructive pulmonary disease (COPD) is an inflammatory obstructive disease of the airways characterized with hypersensitivity of the airway tissues to various allergens, most commonly the fungi contained in the poor-quality hay and straw bedding-Saccharopolyspora rectivirgula, Aspergillus fumigatus, and Thermoactinomyces vulgaris. It is manifested clinically in middle-aged horses with recurrent episodes of dyspnea, chronic cough, and their reduced athletic and working capacity. Pulmonary emphysema and lack of pulmonary collapse are the most common gross lesion. Pathohistological findings in horses with COPD are chronic bronchitis/bronchiolitis, with characteristic changes in lumen, mucosa, submucosa, and smooth muscle layer and alveolar emphysema, both distensive and destructive form. Increased immunoreactivity in lungs and tracheobronchial lymph nodes is also noted. Most common lesions seen on cytology imprint smears from tracheal bifurcation is thick, viscous, PAS-positive mucus that forms Curschmann's spirals. Dominant cell population consists of desquamated airway epithelial cells, as well as eosinophils, neutrophils, mast cells, erythrocytes, and alveolar macrophages. Primary pulmonary pathogens as well as potential contaminants and secondary infection agents were isolated bacteriologically from lung samples. All of the aforementioned findings correlate pointing to the fact that chronic bronchitis/bronchiolitis represents a basic substrate of COPD, which have combined inflammatory and immunological etiology, and emphysema is secondary to airway obstruction. PMID- 17280901 TI - Hit and Lead identification: efficient practices for drug discovery. PMID- 17280902 TI - DPPIV inhibition: promising therapy for the treatment of type 2 diabetes. PMID- 17280903 TI - Recent progress toward nonpeptide ligands for the melanocortin-4 receptor. PMID- 17280904 TI - Tuberculosis chemotherapy: recent developments and future perspectives. PMID- 17280906 TI - Muscle-invasive urothelial carcinoma of the bladder. AB - Muscle-invasive urothelial (transitional cell) carcinoma is a potentially lethal condition for which an attempt at curative surgery is required. Clinical staging does not allow for accurate determination of eventual pathologic status. Muscle invasive urothelial carcinoma is a highly progressive disease, and initiation of definitive therapy within 3 months of diagnosis is worthwhile. Age is not a contraindication for aggressive surgical care, and surgical candidates should be evaluated in the context of overall medical comorbidity. In those patients who undergo surgery, clinical pathways may streamline care. Radical cystectomy remains the "gold standard" of therapy, providing 5-year survival rates of 75% to 80% in patients with organ-confined disease, yet organ-sparing procedures demonstrate clinical effectiveness as well. Cystectomy should be undertaken with the intent of performing complete pelvic lymph node dissection and attaining surgically negative margins. In younger female patients, the preservation of reproductive organs may be achieved in many cases. Prostate- and seminal vesicle preserving cystectomy has been performed, yet the long-term safety and efficacy of such a procedure remains to be determined. Laparoscopic and robotic cystectomy procedures continue to be explored by several investigators. The role of "radical transurethral resection" in muscle-invasive disease is limited to a small cohort of patients, and, when it is performed, cystectomy may be required to consolidate therapy. Postoperative follow-up after cystectomy should occur over short intervals during the first 2 years and can be extended, but not discontinued, beyond that time. Currently, no tumor markers have been prospectively validated to help guide clinical decision making, and prospective trials incorporating marker data should be encouraged. PMID- 17280907 TI - Urinary diversion. AB - A consensus conference convened by the World Health Organization (WHO) and the Societe Internationale d'Urologie (SIU) met to critically review reports of urinary diversion. The world literature on urinary diversion was identified through a Medline search. Evidence-based recommendations for urinary diversion were prepared with reference to a 4-point scale. Many level 3 and 4 citations, but very few level 2 and no level 1, were noted. This outcome supported the clinical practice pattern. Findings of >300 reviewed citations are summarized. Published reports on urinary diversion rely heavily on expert opinion and single institution retrospective case series: (1) The frequency distribution of urinary diversions performed by the authors of this report in >7000 patients with cystectomy reflects the current status of urinary diversion after cystectomy for bladder cancer: neobladder, 47%; conduit, 33%; anal diversion, 10%; continent cutaneous diversion, 8%; incontinent cutaneous diversion, 2%; and others, 0.1%. (2) No randomized controlled studies have investigated quality of life (QOL) after radical cystectomy. Such studies are desirable but are probably difficult to conduct. Published evidence does not support an advantage of one type of reconstruction over the others with regard to QOL. An important proposed reason for this is that patients are subjected preoperatively to method-to-patient matching, and thus are prepared for disadvantages associated with different methods. (3) Simple end-to-side, freely refluxing ureterointestinal anastomosis to an afferent limb of a low-pressure orthotopic reconstruction, in combination with regular voiding and close follow-up, is the procedure that results in the lowest overall complication rate. The potential benefit of "conventional" antireflux procedures in combination with orthotopic reconstruction seems outweighed by the higher complication and reoperation rates. The need to prevent reflux in a continent cutaneous reservoir is not significantly debated, and this should be done. (4) Most reconstructive surgeons have abandoned the continent Kock ileal reservoir largely because of the significant complication rate associated with the intussuscepted nipple valve. PMID- 17280908 TI - Urothelial carcinoma of the prostate. AB - This study was conducted to explore the diagnosis and management of urothelial carcinoma of the prostate in superficial disease and carcinoma in situ, stromal invasion, primary urothelial carcinoma, and urethral recurrence after radical surgery. A consensus conference convened by the World Health Organization (WHO) and the Societe Internationale d'Urologie (SIU) reviewed the diagnosis and management of urothelial carcinoma of the bladder. English-language literature about urothelial carcinoma of the prostate was identified and reviewed. Evidence based recommendations for the diagnosis and management of urothelial carcinoma were made. Many recommendations were level 3 or 4 citations involving the diagnosis and management of superficial urothelial carcinoma; a few were level 2 citations. Level 1 citations related only to chemotherapy and radiotherapy in patients with stromal invasion, although these were not related specifically to invasive prostatic involvement. More than 130 reviewed citations are summarized in this review. Published reports on the diagnosis and treatment of superficial urothelial disease of the prostate primarily consist of short case series from individual centers. Prospective and multicenter trials are needed to identify the real incidence and the best management of these patients. In invasive disease of the prostate, the only large series were designed to investigate invasive bladder cancer. PMID- 17280909 TI - Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. AB - To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Societe Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients with advanced urothelial cancer. A panel of international experts has formulated grade A through D recommendations for the management of patients with locally advanced and metastatic urothelial cancer on the basis of level 1 to 3 evidence and the findings of phase 2 trials, prospective randomized clinical trials, and meta-analyses. PMID- 17280910 TI - Radiotherapy for bladder cancer. AB - The radiotherapy panel met to develop international consensus about the optimal use of radiotherapy, alone or in combination with surgery and chemotherapy, in the radical treatment of patients with bladder cancer. A consensus meeting of experts in the treatment of bladder cancer was convened by the Societe Internationale d'Urologie (SIU). The radiotherapy committee, which had international representation from 6 countries, performed a critical review of the English-language literature and developed evidence-based guidelines for the use of radiotherapy in the treatment of patients with bladder cancer. The strength of the evidence supporting each recommendation was ranked according to a 4-point scale. Consensus statements were developed that address (1) the effectiveness of radiotherapy in the treatment of bladder cancer, (2) the most appropriate patients for curative treatment with radiotherapy, (3) the optimal method of delivery of radiotherapy, (4) the best radiation prescription for treating bladder cancer, and (5) optimal management of the patient's condition after radiotherapy has been provided. Radiotherapy is effective treatment for selected patients with bladder cancer; it produces long-term disease control with preservation of normal bladder function. Modern radiotherapy treatment techniques offer the potential to improve cure rates and reduce adverse effects. All patients in whom the condition is newly diagnosed should be assessed in a multidisciplinary setting, where the relative merits of surgery, radiotherapy, and chemotherapy can be considered on an individual basis with the aim of optimizing overall outcomes. PMID- 17280911 TI - Nonurothelial cancer of the bladder. AB - In this article, we review available evidence on the treatment of patients with nonurothelial cancer of the bladder. More than 150 published works were reviewed in preparation for this summary. Squamous cell carcinoma and adenocarcinoma are ideally treated with radical cystectomy. High-risk groups for these diseases are defined. Small cell carcinoma should be treated with multimodality therapy, including chemotherapy. Other rarer tumors of the bladder are also discussed. PMID- 17280912 TI - Mesenchymal stem cells, could they be the link between tolerance and regeneration? PMID- 17280913 TI - Guidelines for the management of partial-thickness burns in a general hospital or community setting--recommendations of a European working party. AB - Most partial-thickness burns in Europe and the United States are managed by non burns specialists who do not treat burns on a regular basis. To achieve better patient outcomes, partial-thickness burns should be properly managed in non specialist centres and referred to burn units when appropriate. Although some guidelines have been published to assist non-specialists, few have attempted to provide a comprehensive step-by-step guidance emphasising wound-healing principles. A working party of European burn specialists devised a new treatment algorithm to provide clear and current guidance on the management of partial thickness burns in the general hospital and community setting. Four areas were identified for improvement: diagnosis and referral, wound preparation, wound covering and post-wound care. The guidelines take into account the role of wound dressings, infection and general patient well-being, bearing in mind the different working environments that occur across Europe. They are aimed at improving the overall outcome for community-treated patients within the expanding European Union and reducing the number of preventable late referrals to specialists. PMID- 17280914 TI - Fasciectomy is useful for burns in patient with lymphedematous extremity. PMID- 17280915 TI - Management of pain in cancer patients with oral mucositis: follow-up of multiple doses of doxepin oral rinse. PMID- 17280916 TI - Opioid withdrawal: creating more problems. PMID- 17280917 TI - Electroacupuncture as an adjunctive treatment to control neuropathic pain in patients with cancer. PMID- 17280918 TI - Depression and anxiety disorders in palliative cancer care. AB - Depression and anxiety disorders are thought to be common in palliative cancer care, but there is inconsistent evidence regarding their relevance for other aspects of quality of life. In the Canadian National Palliative Care Survey, semi structured interviews assessing depression and anxiety disorders were administered to 381 patients who were receiving palliative care for cancer. There were 212 women and 169 men, with a median survival of 63 days. We found that 93 participants (24.4%, 95% confidence interval=20.2-29.0) fulfilled Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for at least one anxiety or depressive disorder (20.7% prevalence of depressive disorders, 13.9% prevalence of anxiety disorders). The most frequent individual diagnosis was major depression (13.1%, 95% confidence interval=9.9-16.9). Comorbidity was common, with 10.2% of participants meeting criteria for more than one disorder. Those diagnosed with a disorder were significantly younger than other participants (P=0.002). They also had lower performance status (P=0.017), smaller social networks (P=0.008), and less participation in organized religious services (P=0.007). In addition, they reported more severe distress on 14 of 18 physical symptoms, social concerns, and existential issues. Of those with a disorder, 39.8% were being treated with antidepressant medication, and 66.7% had been prescribed a benzodiazepine. In conclusion, it appears that depression and anxiety disorders are indeed common among patients receiving palliative care. These disorders contribute to a greatly diminished quality of life among people who are dying of cancer. PMID- 17280919 TI - Asking the right question of informal caregivers about patient symptom experiences: multiple proxy perspectives and reducing interrater gap. AB - Recent conceptual work on multiple proxy perspectives indicates that clinicians should be more reflective in terms of how they question or prompt informal caregivers to report on patient illness experiences. There are different ways in which therapeutic questions might be posed that can influence perceptual agreement between patients and caregivers. The purpose of this randomized, between-subjects study was to test the hypothesis that "The interrater gap between patient self-assessment and caregiver assessment on patient multidimensional symptom experiences will be reduced when caregivers are prompted to imagine-patient perspective-take." We also tested the hypothesis that "Regardless of the perspective-taking prompt provided to the caregiver, gender will have no impact on patient and caregiver discrepancy scores on patient symptom experiences." This study comprised a convenience sample of 126 dyads consisting of breast and prostate cancer patients, and their informal caregivers. Patients provided self-reports on the abbreviated Memorial Symptom Assessment Scale (MSAS). Informal caregivers also completed the abbreviated MSAS under one of three randomly assigned instructional set conditions: neutral, imagine-patient perspective-taking, and imagine-self perspective-taking. The imagine-patient prompt was effective in reducing caregiver discrepancy across symptoms and underlying dimensions in comparison to the imagine-self prompt. However, the least discrepancy between patients and caregivers occurred in the neutral condition. The greatest discrepancy by caregivers occurred in imagine-self condition. For the most part, there was no significant interaction effect between caregiver gender and induced perspective-taking across each of the symptoms and underlying frequency, severity, and distress. These results lend support for Pickard and Knight's multiple proxy perspectives model in that different perspective-taking prompts can result in varying levels of perceptual agreement, of which clinicians need to be aware to deliver sensitive patient and family centered care. PMID- 17280920 TI - Factors influencing agreement in symptom ratings by lung cancer patients and their significant others. AB - Comparisons of symptom ratings and health-related quality of life between significant others and patients have been the focus of numerous studies during the past decades. Additional studies are needed to assess the discrepancies identified in this work. In the present cross-sectional exploratory study, focus has been on evaluating the accuracy of significant other proxy ratings and on investigating factors that influence agreement between lung cancer patients and significant others based on dyadic assessments from 52 patients and 54 significant others. Results indicate that the levels of agreement are fair to good, but that significant others consistently rate the patients' symptoms higher and functioning lower than the patients do themselves. Factors found to influence agreement in various dimensions of symptoms and functioning were gender, patient age, and significant others' self-reported lack of family support, health problems, and caregiver esteem. PMID- 17280921 TI - Chemosensory dysfunction is a primary factor in the evolution of declining nutritional status and quality of life in patients with advanced cancer. AB - Alterations in taste and smell functions have been reported in cancer patients. Although these senses are known to be particularly affected by chemotherapy, many features of chemosensory perception in cancer patients remain obscure. The relative importance of chemosensory changes in the etiology of malnutrition and wasting is not known. To assess this relationship, self-perceived taste and smell function were evaluated using a validated questionnaire in 66 patients with advanced cancer receiving palliative care (median survival 7.4 months). Participants also completed 3-day food records to assess dietary intake, and the Functional Assessment of Anorexia/Cachexia Therapy questionnaire to assess quality of life (QOL). Total chemosensory complaint scores ranged from 0 to 14 on a 16-point scale. Only 14% of the subjects reported no chemosensory complaints of any kind, whereas 86% reported some degree of chemosensory abnormality. The most common complaints were persistent bad taste in the mouth, taste distortion, and heightened sensitivity to odors. Subjects with severe chemosensory complaints showed substantially lower energy intakes (by 900-1,100 kcal/day), higher rates of weight loss, and lower QOL scores than subjects with mild or moderate chemosensory complaints. Severe chemosensory dysfunction is persistent well beyond the window of active therapy in patients with advanced cancer and represents a primary factor relating to malnutrition, wasting, and poor QOL. Further research is required to identify appropriate strategies to alleviate this important group of symptoms, to determine whether intervention will improve QOL, and to match foods and diet to the unique chemosensory profile of advanced cancer patients. PMID- 17280923 TI - Taiwanese version of the M. D. Anderson symptom inventory: symptom assessment in cancer patients. AB - The purpose of this study was to validate the Taiwanese version of the M. D. Anderson Symptom Inventory (MDASI-T) in a sample of 556 Taiwanese patients with multiple diagnoses of cancer. The internal consistency Cronbach alpha was 0.89 for symptom severity items and 0.94 for interference items. The test-retest reliability was 0.97 for the severity composite score and 0.96 for the interference composite score over a 3-day interval in a sample of 12 patients. Construct validity was established by factor analysis, which revealed a two factor structure. Concurrent validity was examined by correlating the MADSI-T scores and scores of the Medical Outcome Study 36-Item Short-Form Health Survey. Known-group validity was established by comparing MDASI-T scores between patients having low functional status and those having high functional status (Karnofsky Performance Status scores50, respectively) and between inpatients and outpatients. The MDASI-T's sensitivity (its ability to detect small differences in reporting variations) was examined by comparing the MDASI-T composite symptom scores and composite interference scores before, during, and one week after treatment in a sample of 20 breast cancer patients receiving chemotherapy. The MDASI-T is a reliable, valid, and sensitive instrument for measuring the severity and interference with daily life of cancer-related symptoms among Taiwanese cancer patients. PMID- 17280922 TI - Dysfunction in multiple primary afferent fiber subtypes revealed by quantitative sensory testing in patients with chronic vincristine-induced pain. AB - Vincristine is one of the frontline chemotherapy drugs for the treatment of numerous lymphoid neoplasias. The main dose-limiting complication of vincristine is the development of painful peripheral neuropathy. Although clinical reports have appeared in the literature detailing the symptoms of vincristine neuropathy, quantitative sensory testing data that might yield insight to dysfunction in subsets of primary afferents are lacking. In this report, pain descriptors and anatomical distributions of sensory abnormalities were collected in each patient. Touch detection threshold, sharpness detection threshold, the thresholds for the detection of skin warming, heat pain, skin cooling, and the perception of cooling induced pain were measured in patients with chronic vincristine-induced pain in each area of sensory abnormality and in skin perceived as outside the affected areas. Elevated touch detection thresholds were observed both within and outside areas affected by pain and sensory abnormality. Elevated sharpness and warm detection thresholds were noted only in areas affected by pain. These data suggest that chronic vincristine-induced pain is associated with dysfunction in Abeta, Adelta, and C caliber primary afferent fibers. Deficits in Abeta fibers appear to precede and presage deficits in the other fiber types, whereas deficits in Adelta- and C-fiber function appear to be specifically associated with the generation of pain. PMID- 17280924 TI - Validation of the Missoula-Vitas Quality-of-Life Index among patients with advanced AIDS in urban Kampala, Uganda. AB - The Missoula-Vitas Quality-of-Life Index (MVQOLI) is a unique tool specifically designed to measure quality of life (QOL) in advanced illness in a palliative care setting. The aim of this study was to explore its cross-cultural validity. We used a culturally adapted version in a local language, Luganda, and tested the MVQOLI-M in 200 patients with advanced AIDS in urban Kampala, Uganda. Content validity was assessed using the content validity ratio approach. Reliability was assessed using Cronbach's alpha (alpha), and test-retest reliability was evaluated using the intraclass correlation coefficient. All items and domains were rated content valid and there was good construct validity. The instrument demonstrated good internal consistency (alpha=0.83). The transcendence domain was the best predictor of overall QOL. The MVQOLI-M is an acceptable, valid, and reliable measure of QOL for people with advanced AIDS and findings demonstrate the importance of measuring the transcendence domain in QOL in advanced illness. PMID- 17280925 TI - A double-blind comparison of a supplemental interligamentary injection of fentanyl and mepivacaine with 1:200,000 epinephrine for irreversible pulpitis. AB - The analgesic efficacy of supplemental interligamentary fentanyl injection for management of endodontic debridement patients was investigated through a randomized, double-blind study. Forty patients who presented with acute symptomatic irreversible pulpitis of the upper first molar tooth participated in the study. Patients were scheduled for endodontic debridement, for which infiltration anesthesia with 1.8 ml of 2% mepivacaine with epinephrine 1:200,000 was the standard primary anesthetic technique. Patients were randomly divided into two equal groups. The first group received supplemental interligamentary injection with 0.4 ml fentanyl 0.05 mg/ml, while the second group received supplemental interligamentary injection with 0.4 ml mepivacaine with epinephrine 1:200,000. The intraligamental-injected drug was given as 0.2 ml on the mesial and 0.2 ml on the distal aspect of the tooth. Results indicated that fentanyl provided relatively greater analgesia, yielding satisfactory relief during different stages of the procedure, including access cavity preparation, pulpotomy, and pulp extirpation. Fentanyl is effective when used in conjunction with local anesthetics to provide adequate analgesia during endodontic debridement, and this finding provides strong evidence that peripheral actions are involved in the analgesia produced by opioid drugs in inflammatory pain. PMID- 17280926 TI - Sex and age differences in coping styles among children with chronic pain. AB - The purpose of this study was to examine sex and age differences in coping strategies among pediatric patients with chronic pain. Sex differences are reported in the adult pain and coping literatures, but little attention has been given to possible distinctions in coping styles in the pediatric chronic pain population. Investigating pain coping skills at an early age may provide clinicians with a better understanding of the evolution of characteristic coping styles and identify areas for intervention. Pain intensity (Visual Analog Scale), pain coping strategies (Pain Coping Questionnaire), and coping efficacy were assessed in children (ages 8-12 years) and adolescents (ages 13-18 years), presenting to a pediatric chronic pain clinic (n=272). Significant sex differences in coping strategies were found. After controlling for pain intensity, girls used social support seeking more than boys, while boys used more behavioral distraction techniques. Adolescents engaged in more positive self statements (a cognitive strategy) than children. Both boys and girls showed a trend toward pain coping efficacy being negatively correlated with average pain intensity. For girls, pain coping efficacy was also significantly negatively correlated with internalizing/catastrophizing. However, no sex or age differences in coping efficacy were found. This study demonstrates the early emergence of sex and aged-based preferences in coping strategies among children and adolescents with chronic pain. The findings establish a basis for further research on early social influences in the development of pain coping styles in males and females. Implications for further clinical research in this area are discussed. PMID- 17280927 TI - Medical treatment for inoperable malignant bowel obstruction: a qualitative systematic review. AB - The use of symptomatic agents has greatly improved the medical treatment of advanced cancer patients with inoperable bowel obstruction. A systematic review of studies of the most popular drugs used in the medical management of inoperable malignant bowel obstruction was performed to assess the effectiveness of these treatments and provide some lines of evidence. Randomized trials that involved patients with a clinical diagnosis of intestinal obstruction due to advanced cancer treated with these drugs were reviewed. Five reports fulfilled inclusion criteria. Three studies compared octreotide (OC) and hyoscine butylbromide (HB), and two studies compared corticosteroids (CSs) and placebo. Globally, 52 patients received OC, 51 patients received HB, 37 patients received CSs, 15 patients received placebo, and 37 patients received both placebo and CSs. On the basis of these few data, the superiority of OC over HB in relieving gastrointestinal symptoms was evidenced in a total of 103 patients. The latter studies had samples more defined in terms of stage and inoperability, and had a shorter survival in comparison with studies of CSs (less than 61 days, most of them less than 20 days). Data on CSs are less convincing, due to the methodological weakness of existing studies. This review confirms the difficulties in conducting randomized controlled trials in this population. PMID- 17280928 TI - The steroid withdrawal syndrome: a review of the implications, etiology, and treatments. AB - Steroid therapy is frequently used for chronic pain, particularly inflammatory pain states. Steroid withdrawal syndrome can produce a broad array of signs and symptoms, some of which are not well recognized. High fever is among these. We describe several cases with this clinical scenario and review the syndrome in broader terms. PMID- 17280929 TI - Development of the APCA African Palliative Outcome Scale. PMID- 17280935 TI - Anthrax toxin receptors and infantile systemic hyalinosis. PMID- 17280936 TI - Diabetic foot disorders. A clinical practice guideline (2006 revision). AB - The prevalence of diabetes mellitus is growing at epidemic proportions in the United States and worldwide. Most alarming is the steady increase in type 2 diabetes, especially among young and obese people. An estimated 7% of the US population has diabetes, and because of the increased longevity of this population, diabetes-associated complications are expected to rise in prevalence. Foot ulcerations, infections, Charcot neuroarthropathy, and peripheral arterial disease frequently result in gangrene and lower limb amputation. Consequently, foot disorders are leading causes of hospitalization for persons with diabetes and account for billion-dollar expenditures annually in the US. Although not all foot complications can be prevented, dramatic reductions in frequency have been achieved by taking a multidisciplinary approach to patient management. Using this concept, the authors present a clinical practice guideline for diabetic foot disorders based on currently available evidence, committee consensus, and current clinical practice. The pathophysiology and treatment of diabetic foot ulcers, infections, and the diabetic Charcot foot are reviewed. While these guidelines cannot and should not dictate the care of all affected patients, they provide evidence-based guidance for general patterns of practice. If these concepts are embraced and incorporated into patient management protocols, a major reduction in diabetic limb amputations is certainly an attainable goal. PMID- 17280937 TI - Neurodynamics in a broader perspective. PMID- 17280938 TI - DIRE: a tool to assess risks of maintaining opioid treatment. PMID- 17280940 TI - Decision of Cirrhosis Using Liver's Ultrasonic Images. AB - Feature extraction techniques in the ultrasonic images of a liver were studied firstly. As an initial result, total 25 parameters relating to cirrhosis were extracted. They were obtained from the motion curve of the liver in an M-mode image, and from the texture using a B-mode image. Then the efficiency of every parameter was analyzed, and with the use of a feature fusion method a set of 20 useful features was picked out. With these chosen features, a noninvasive automatic decision system for cirrhosis was constructed based on a Fisher linear decision criterion. The clinical application for 43 cases showed that this quantitative system was effective in the diagnosis of cirrhosis. PMID- 17280941 TI - Development of a simple diagnostic method for the glaucoma using ocular Fundus pictures. AB - There are approximately 2 million people who have glaucoma. And about 90% of glaucoma patients have chronic type disease, and most of them do not notice of their disease. Finally they will lost their eyesight by this disease. Therefore, it is necessary to develop the auto diagnostic method for glaucoma. Our objective of this study is the development of the auto diagnostic system for the glaucoma by using fundus photograph. In our system, digitized fundus photograph is tested in personal computer, and the ratio of the area of optic disk and the area of optic disk cup (named C/D ratio) is calculated and evaluated automatically. And then this system can checkup subject condition for glaucoma. In this paper, we will discuss our auto diagnostic system for the glaucoma. PMID- 17280942 TI - Feature-based texture display for detection of polyps on flattened colon volume. AB - This paper presents a volume-based algorithm to flatten the colon. Based on the flattened colon volume, three different display schemes are adapted to transfer the three-different imensional (3D) flattened colon volume into a 2D image. One display scheme is surface-based rendering, one is volume-based rendering, and the third one is feature-based texture display. These three displays generate not only a traditional flattened-colon surface image, but also a feature-based texture image which can be utilized to characterize and detect the colonic polyps, resulting in a new way to visualize the entire colon. PMID- 17280943 TI - A 2-d active appearance model for prostate segmentation in ultrasound images. AB - In this research we use an active appearance model (AAM) as the core of a robust segmentation algorithm that combines contour and texture information to learn shape variability through a training procedure in trans-rectal ultrasound (TRUS) images of the prostate. Training was carried out using a dataset of 95 images which are preprocessed using gray-level mathematical morphology operators. Preliminary results are promising. The segmentation can provide shapes that have an overlap with respect to a ground truth shape, traced by an expert, of up to 96%, and an average distance from point to curve of up to 1.3 pixels. PMID- 17280944 TI - Fast automatic segmentation of nuclei in microscopy images of tissue sections. AB - In this paper, we present a segmentation method for nuclei in microscopy images of tissue sections. The proposed method is completely automatic and performs well in the conflicting aims of speed efficiency, detection accuracy and shape fitting. It proposes an efficient alternative to existing methods ([1], [4]), in achieving the three main usual segmentation steps: (i) background extraction, (ii) seed finding and (iii) seed growing. Eventually, some significant results are depicted and discussed. PMID- 17280945 TI - Leukocyte segmentation and classification in blood-smear images. AB - The detection and classification of leukocytes in blood smear images is a routine task in medical diagnosis. In this paper we present a fully automated approach to leukocyte segmentation that is robust with respect to cell appearance and image quality. A set of features is used to describe cytoplasm and nucleus properties. Pairwise SVM classification is used to discriminate between different cell types. Evaluation on a set of 1166 images (13 classes) resulted in 95% correct segmentations and 75% to 99% correct classification (with reject option). PMID- 17280946 TI - Segmentation of brain from computed tomography head images. AB - An algorithm to determine the human brain (gray matter (GM) and white matter (WM)) from computed tomography (CT) head volumes with large slice thickness is proposed based on thresholding and brain mask propagation. Firstly, a 2D reference image is chosen to represent the intensity characteristics of the original 3D data set. Secondly, the region of interest of the reference image is determined as the space enclosed by the skull. Fuzzy C-means clustering is employed to determine the threshold for head mask and the low threshold for brain segmentation. The high threshold is calculated as the weighted intensity average of the boundary pixels between bones and GM/WM. Based on the low and high thresholds, the CT volume is binarized, followed by finding the brain candidates through distance criterion. Finally the brain is identified through brain mask propagation using the spatial relationship of neighboring axial slices. The algorithm has been validated against one non-enhanced CT and one enhanced CT volume with pathology. PMID- 17280947 TI - Image registration for breast imaging: a review. AB - Breast cancer is the most common type of cancer in women worldwide. About ten percent of women are confronted with breast cancer in their lives. Breast Cancer can be most efficiently treated if detected at an early sage. Imaging of the breast can be accomplished using several modalities such as: X-ray, MRI, CT, Ultrasound, and now Molecular Imaging. Image registration plays a critical role in breast imaging. It provides aid to better visualization of lesions on bilateral or temporal X-ray mammograms, or in the fusion of different modalities acquired using different principles of physics. The non-rigid, inhomogeneous, anisotropic and temporally changing nature of breast tissue make breast image registration a challenging task. This paper presents an overview of the current state-of-the-art in the breast image registration techniques. Methods are classified according to the modalities involved in the registration process. Intra-modality registration techniques focus on X-ray mammogram registration, while inter-modality techniques will cover the registration of X-ray with other modality. Validation of breast registration methods is also discussed. PMID- 17280948 TI - The Processing of the Degraded Medical Digital Image's Image Enhancement. AB - Image's noise, edge and contrast are the important factors that influence image's quality. If a method of image enhancement is solely applied to the degraded medical digital image, image's quality is improved in part, if a combined method of image enhancement is applied to the degraded medical digital image, it can increase the image's quality greatly. PMID- 17280949 TI - Image enhancement method for fingerprint recognition system. AB - Image enhancement plays an important role in Fingerprint Recognition System. In this paper fingerprint image enhancement method, a refined Gabor filter, is presented. This enhancement method can connect the ridge breaks, ensures the maximal gray values located at the ridge center and has the ability to compensate for the nonlinear deformations. The result shows it can improve the performance of image enhancement. PMID- 17280950 TI - Global optimization of medical image registration based on nonlinear correlation measurement. AB - A global optimization technique for image registration using the concept of nonlinear correlation information entropy (NCIE) as the matching criterion is presented. The method makes it possible to efficiently overcome the local minima problem utilizing the extremum property of NCIE. Furthermore, the improved downhill simplex algorithm incorporated variant accuracy tolerance can reduce the evaluation times greatly as well as obtain an accurate and optimal transformation. Applying to register the magnetic resonance images of brain, the global optimization technique shows the validity and robustness in global searching range. PMID- 17280951 TI - A New Multi-phase Level Set Framework for 3D Medical Image Segmentation Based on TPBG. AB - In this paper, we propose a new multi-phase level set framework for 3D medical image segmentation to deal with the limitation of 2-phase segmentation algorithms using one level set. By developing the technique of painting the background with average gray level of the object (TPBG) and reusing the active contours model without edges [1] which is 2-phase one, we are able to obtain more than two segments (n-1 times for n phases, n>1). Following the philosophy of dichotomy, we illustrate the efficiency of the proposed framework by segmenting a 3D medical image into more than two segments step by step. PMID- 17280952 TI - An Adaptive Enhancement Algorithm for CT Brain Images. AB - We present an adaptive smoothing filter aiming to improve the visibility and detectability of the obscuration of the lentiform nucleus, which is one of the early signs of acute cerebral artery infraction, in CT brain images. The proposed method is able to enhance image data by removing noise without significantly blurring the structures in the images. This method is tested both on computer simulated image data and on clinical CT brain images. Moreover, a comparison of the proposed method to two commonly used techniques is made. Preliminary results demonstrate the superiority of the proposed method and its usefulness for detecting the obscuration of the lentiform nucleus, which could not be detected previously without using the proposed method. PMID- 17280953 TI - Novel Anisotropic Diffusion Algorithm Based on PID Control Law Together with Stopping Mechanism. AB - Anisotropic diffusion is one of the widely used techniques in the field of image process. Tremendous applications show promising results by using anisotropic diffusion algorithm or its revisions. In this paper, we propose a new anisotropic diffusion method which is based on PID (Proportional-Integral-Derivative) control law together with a stopping mechanism. The PID control law is a simple and intuitive law in cybernetics and it has been proven to be effective to improve the system's performance. In this new approach, according to the different processing purpose for edge and noise, different PID control parameters are chosen. Therefore, anisotropic diffusion approach is carried out more efficiently. Moreover, the proposed stopping mechanism is based on the linear correlation theory, which indicates the similarity of two images. Incorporating with this mechanism, anisotropic diffusion is able to stop automatically when the processed image reaches the certain predefined performance target. The experiments show the correctness and effectiveness of the proposed method. PMID- 17280954 TI - A fragile watermarking scheme for medical image. AB - The infrastructure to deploy security standards is often lacking during modern telemedicine. As a branch of watermarking technique, the fragile watermarking provides us a good solution to the authentication for telemedicine. A fragile watermarking algorithm based on least significant bit (LSB), hash function and chaotic sequence is presented in this paper. To resist counterfeiting attack, the watermark signal is extracted from the original image, so different image has different watermark signal. The watermark signal is then processed by exclusive OR (XOR) operation with the chaotic sequence in order to increase the security of the watermarking algorithm. Finally, it is embedded in the LSB of the host image. The experimental results show that the watermark is invisible; the watermark algorithm has good ability to resist counterfeiting attacks. Furthermore, after the watermark is extracted from the watermarked image, it is exactly the same as the original one. This kind of watermarking algorithm can e used for real-time diagnosis. PMID- 17280955 TI - Simulating imaging with the scanning ion-conductance microscope. AB - The Scanning Ion-Conductance Microscope (SICM) is a member of the family of Scanned Probe Microscopes (SPM). Examples include the Scanning Electrochemical Microscope (SECM) and Atomic Force Microscope (AFM). SICM uses the ion concentration field at the tip of a micropipette filled with an electrolyte solution as a probe to generate images of sample topography. As with other members of the SPM family, the probe geometry determines the observed image. This paper presents mathematical models for simulating the SICM in its different operating modes with the intent of creating a framework within which the effect of probe-geometry can be studied. We validate our model by comparing simulated approach-curves with empirical data. Finally, we show simulated images of a Gaussian-bump substrate under the different operating modes of the SICM. PMID- 17280956 TI - A novel method for breast cancer prognosis using wavelet packet based neural network. AB - This paper presents an approach for early breast cancer diagnostic by employing combination of artificial neural networks (ANN) and wavelet based subband image decomposition which detect microcalcification in digital mammograms. The microcalcifications correspond to high-frequency components of the image spectrum, detection of microcalcifications is achieved by decomposing the mammograms into different frequency subbands, suppressing the low-frequency subband, and finally, reconstructing the mammogram from the subbands containing only high frequencies. For this approach we employed different types of wavelet packets. We used the result as an input of neural network for classification. The proposed methodology is tested using the Nijmegen and the Mammographic Image Analysis Society (MIAS) mammographic databases and images collected from local hospitals. Results are presented as the receiver operating characteristic (ROC) performance and are quantified by the area under the ROC curve. PMID- 17280957 TI - Multiresolution medical image segmentation based on wavelet transform. AB - The wavelet transform always is used to analyze image. The watershed transformation is a useful morphological segmentation tool for a variety of grey scale image. In this paper, an efficient segmentation method for medical image analysis is presented, which combines pyramidal image segmentation with hierarchical watershed segmentation algorithm. The segmentation procedure consists of pyramid representation, image segmentation, region merging and region projection. Each layer of pyramid is split into a number of regions by a root labeling technique, and the regions are projected onto next higher-resolution layer by reverse wavelet transform. The projection gradually achieve onto full resolution layer so that segmentation is ended. Morphologic operation is used to smooth original image while filtering out noise. We have applied our new approach to analyze medical image. Experimental results demonstrate the method effective. PMID- 17280958 TI - Method of Reducing Dimensions of Segmentation Feature parameter Applied to Skin Erythema Image Segmentation. AB - In this paper we discussed the method to reduce dimensions of segmentation feature applied to skin erythema image segmentation. Basing on analyzing a lot of erythema images, we proposed a new segmentation feature parameter applied to skin erythema image segmentation. At last, by using the fuzzy-c-means cluster arithmetic, we compared the segmentation speed and segmentation effect of adopting different segmentation features parameter and found that the segmentation result by using the new segmentation feature parameter is better. PMID- 17280959 TI - Study of marrow cell image compression based on quantization threshold. AB - In this paper, six integer wavelet transforms are compared on marrow cell image energy distribution and their percentage of zero coefficients in every subband for higher performances of marrow cell image compression. PMID- 17280961 TI - Color image diffusion using adaptive bilateral filter. AB - In this paper, we propose an approach to diffuse color images based on the bilateral filter. Real image data has a level of uncertainty that is manifested in the variability of measures assigned to pixels. This uncertainty is usually interpreted as noise and considered an undesirable component of the image data. Image diffusion can smooth away small-scale structures and noise while retaining important features, thus improving the performances for many image processing algorithms such as image compression, segmentation and recognition. The bilateral filter is noniterative, simple and fast. It has been shown to give similar and possibly better filtering results than iterative approaches. However, the performance of this filter is greatly affected by the choose of the parameters of filtering kernels. In order to remove noise and maintain the significant features on images, we extend the bilateral filter by introducing an adaptive domain spread into the nonlinear diffusion scheme. For color images, we employ the CIE Lab color system to describe input images and the filtering process is operated using three channels together. Our analysis shows that the proposed method is more suitable for preserving strong edges on noisy images than the original bilateral filter. Empirical results on both nature images and color medical images confirm the novel method's advantages, and show it can diffuse various kinds of color images correctly and efficiently. PMID- 17280960 TI - An Efficient Colon Segmentation method for Oral Contrast-Enhanced CT Colonography. AB - A new method for fully automated segmentation of the colonic walls in volumetric CT data is proposed. Because each dataset requires long process time, this paper will focus on the development of an efficient segmentation method in half-sized volume data by an anatomical-oriented approach. The process utilizes global and local histograms of Contrast Enhanced Fluids (CEF) to generate adaptive thresholds in oral contrast-enhanced CT for making two major binary masks. We applied a restricted "dilation"operation on an air binary mask for seeds generation and region growing. This method can surf all of colon lumen and extract all parts of it, even those might be submerged by CEF. The subjective and objective validation demonstrated that the error of leakage to extra colonic can be minimized. The procedures described could be the first stage in every multi stage colon lumen extraction and analysis. PMID- 17280962 TI - An efficient medical image compression scheme. AB - In this paper, a fast lossless compression scheme is presented for the medical image. This scheme consists of two stages. In the first stage, a Differential Pulse Code Modulation (DPCM) is used to decorrelate the raw image data, therefore increasing the compressibility of the medical image. In the second stage, an effective scheme based on the Huffman coding method is developed to encode the residual image. This newly proposed scheme could reduce the cost for the Huffman coding table while achieving high compression ratio. With this algorithm, a compression ratio higher than that of the lossless JPEG method for image can be obtained. At the same time, this method is quicker than the lossless JPEG2000. In other words, the newly proposed algorithm provides a good means for lossless medical image compression. PMID- 17280963 TI - Vessel Boundary Detection for its 3D Reconstruction by Using a Deformable Model (GVF Snake). AB - Vessel boundary detection and 3D modeling is a difficult but necessary task in analyzing the mechanics of inflammation and the structure of the microvasculature. We present in this paper a method of analyzing this structure by the means of the deformable model (using GVF Snake) for vessel boundary detection and three-dimensional reconstruction. For this purpose, we used a virtual vessel model and produced synthetic images. From these images, we obtained contours of vessels by the GVF Snake and then reconstructed a three dimensional structure by using the coordinates of the Snakes. PMID- 17280964 TI - Multiple digital watermarking applied to medical imaging. AB - Beyond its already established wide range of applications, digital watermarking has recently started to gain a foothold in the healthcare sector. The paper discusses the potential of multiple watermarking to address a number of health information management issues, such as protection of sensitive data, origin and data authentication, image archiving and retrieval. A wavelet-based multiple watermarking scheme focusing on these medical-oriented applications is presented; the scheme allows the physician to define a Region of Interest, whose diagnostic value is explicitly protected throughout the embedding process, since the only additional information inserted therein is for the purpose of integrity control. The rest part of the image casts multiple watermarks conveying the physician's digital signature, patient's sensitive data, and keywords allowing image retrieval. In order to increase data robustness, a form of hybrid coding is applied, which includes repetitive embedding of BCH encoded watermarks. PMID- 17280965 TI - Non-contact Breath Motion Monitor ing System in Full Automation. AB - It is said that sleep apnea syndrome is one of the main causes of airplane, train and car accidents. We have developed a non-contact breathing measurement system which diagnoses not only sleep apnea syndrome but also other sleep disorders. This system calculates the amount of the volume change and makes the movement of the outside of the body by the breath motion visible. If the patient is breathing abnormally, we are able to recognize the appearance of abnormality at a glance and know the amount of the volume change in that location. To verify the amount of the volume change, we compare the amount of ventilation measured with a spirometer to the amount of volume change measured with this system. As a result, there is a high correlation in the amount of the volume change and the amount of ventilation in any sleeping position. PMID- 17280966 TI - Study of the Practical Post-processing Arithmetic on MRI. AB - BOLD-fMRI is an experiment method which is used for magnetic resonance image technology to detect physiological change of different brain functional neural activity under different stimulation conditions. In this paper, we study post processing arithmetic of human brain's fMRI under the condition of acupuncture to obtain the brain's activation region. In order to overcome the interference produced by fake shadow, the rotation transformation technology was used for registration of the images. Maximum mutual information method was proposed and used to increase the image's character. By computing the relative coefficients between rest time and activation time, functional region and non-functional region can be effective detected. The experiment results show functional activity region processed by this method is close to theoretical prediction. PMID- 17280967 TI - Thermographic investigation of the heating effect of high intensity focused ultrasound. AB - The purpose of this study was to use thermal imaging camera to investigate the localised heating effect of High intensity focused ultrasound (HIFU), to monitor temperature rise in real time and accurately. In order to visualise thermally induced protein coagulation, a phantom of Polyacrylamide (PAA) gel containing fresh egg albumin was used as tissue mimicking material. A high resolution thermal camera was positioned directly over the samples to record thermal fluctuations. Two modes of ultrasound were investigated, i.e. continuous wave and pulsed wave. Through imaging processing and thermal analysis, the temperature profile of the phantoms during HIFU heating was obtained, and the optimised parameters for protein coagulation were identified. The experiments have shown that thermal imaging is an effective way to measure the bioheating effect of HIFU. PMID- 17280968 TI - Blind Deconvolution for Symmetric Point-spread Functions. AB - Blind deconvolution is to restore a blurred image without full information of the associated point-spread function (PSF). One recent method is to formulate an equation with only the image as unknowns by eliminating the PSF because of its symmetric property. The original image is then recovered by solving the latter equation. We present a theoretical analysis for this method in this paper. After formulating the problem in terms of the Z-transforms, it is proved that the deconvolved solutions with this method are up to a constant under additional practical assumptions on the images. We also provide a preliminary numerical experiment with a practical phantom to demonstrate the feasibility of this method. PMID- 17280969 TI - Vector Interpolation Method in Three-dimensional Reconstruction of Tissue Doppler Echocardiography. AB - A new method of vector interpolation in three-dimensional reconstruction of tissue Doppler echocardiography is developed and applied to the clinical research. Both the amplitude and direction information of functional parameters, such as velocity or acceleration, in tissue Doppler images is utilized to reconstruct dynamic three-dimensional vector field of myocardial tissue motion. The reconstructed three-dimensional field tissue motion can be visualized simultaneously with the three-dimensional anatomical structure to express the correlation between them. Clinical human experiments show that reconstructed results are consistent with the physiological characteristics of the heart. This method may have potential application in the study of cardiac electrophysiology. PMID- 17280970 TI - An Adaptive-Tabu GA for Registration of CT and Surface Laser Scan. AB - An adaptive-tabu GA (Genetic Algorithm) method is proposed to improve some traditional GA methods in the registration of computer tomography (CT) and surface laser scan. In this method, the adaptive memory structure and search strategy of Tabu Search (TS) with the modified chromosome crossover and adaptive mutation are proposed to increase the convergence speed and accuracy of the fitness function. This registration method can be used on non-fiducial stereo tactic brain surgeries to assist surgeons to diagnose and treat brain diseases. PMID- 17280971 TI - Detection of luminal contour using fuzzy clustering and mathematical morphology in intravascular ultrasound images. AB - An innovative application of fuzzy clustering and mathematical morphology for the problem of luminal contour detection in intravascular ultrasound images is presented. Median and standard deviation are used as features for segmentation process. Comparison was made with gold standard segmented images obtained from the average of images segmented by experienced medical doctors. Tests were carried out with 20 in vivo coronary images obtained from different patients. High correlation coefficients were found between lumen regions manually and automatically defined when area, mean gray level, and standard deviation of the lumen regions were compared. PMID- 17280972 TI - Effect of adaptive-neighborhood contrast enhancement on the extraction of the breast skin-line in mammograms. AB - Extraction of the breast skin-line is crucial in computeraided analysis of mammograms. This paper presents an analysis of the effect of adaptive neighborhood contrast enhancement (ANCE) [1] on skin-line extraction. ANCE is used to enhance the parenchyma of the breast and suppress the background noise. Suppression of the background noise can improve skin-line extraction. Our skin line extraction method is based on the work by Ojala et al. [2]. We use the Hausdorff distance [3, 4] for quantitative comparison of the skin-lines. Our work shows that ANCE improves the skin-line extraction due to its ability of suppressing noise while improving the contrast. We have defined an improvement factor based on the Hausdorff distance. The metric allows us to spot automatically the mammograms with significant improvement in the detection of the skin-line because of ANCE. We tested 83 images from the MIAS database [5], with the ground-truth skin-lines hand-drawn by a radiologist [6]. The average Hausdorff distance improvement with ANCE was 11 pixels (2.2 mm). PMID- 17280973 TI - Conductive rubber electrode for wearable health monitoring. AB - For the continuous health monitoring, physiological signal must be able to measure for a long time in daily life. Therefore, health monitoring device was made as small as possible, and sensors must have a small effect by motion artifact. To reduce impedance between the user skin and the electrode, a conductive gel was applied to the metallic electrode, thereby facilitating converting ion current flowing in a living body into an electric current. However, commercial disposable electrode using the conductive gel incurred a skin trouble such as a reddish skin and stinging pain, when used to measure electrocardiogram (ECG) for a long-time. In this paper, we evaluated the performance of the conductive rubber electrode to use the electrode of wearable health monitoring device. These electrode were made the rubber electrode included a good conductive metal compound and had some viscosity. In addition, conductive yarn was tested to replace connecting wire between electrode and measurement device. The ECG signal measured by the conductive yarn rubber electrode cable was good quality. However, conductive yarn must be isolated to use in garment. PMID- 17280974 TI - A comparison of continuous wave Doppler radar to impedance cardiography for analysis of mechanical heart activity. AB - The paper compares the data obtained from a continuous wave Doppler radar sensor based on a commercially available microwave motion sensor KMY24 to an impedance cardiograph measured using a Cardiac Output Monitor (Medis Niccomo). Both sensors are used to analyze the mechanical activity of the heart. System parameters, signal content and robustness are discussed. PMID- 17280975 TI - Tracking based baseline restoration for acquisition of impedance cardiogram and other biosignals. AB - Most of the biosignals have a baseline which may drift over a large range compared to the excursion of the signal of interest. To make effective use of the input dynamic range of the signal acquisition setup, this offset drift needs to be cancelled. The circuit reported here uses amplitude tracking technique for estimation and removal of the baseline drift. This circuit is independent of the processor to which the signal acquisition unit is interfaced. PMID- 17280976 TI - Identification of Vascular Dynamics and Estimation of the Cardiac Output Waveform from Wearable PPG Sensors. AB - A method for estimating cardiovascular dynamics and cardiac output waveforms using signals derived from two PPG sensors is presented. The method employs a novel signal-processing algorithm known as Laguerre Model Blind System Identification to identify the vascular dynamics associated with the measured PPG signals. A unique deconvolution method is then used with the identified Laguerre models to estimate the cardiac output waveform. Initial results implementing the method on data derived from a human subject is presented. Results show good agreement between the morphology of the estimated waveform and the typical morphology of the human cardiac output waveform. PMID- 17280977 TI - A CMOS Camera-Based Pulse Oximetry Imaging System. AB - In this paper a CMOS camera-based system for non-contact pulse oximetry imaging in transmission mode is described. Attention is drawn to the current uses of conventional pulse oximetry and the potential application of pulse oximetry imaging to developing objective wound assessment systems. PMID- 17280978 TI - A Multi Parameters Wearable Telemetric System for Cardio-Pulmonary Fitness of e Health. AB - We report a multi parameters cardio-pulmonary (CP) monitoring system with features of low power consumptions (30mA,3.3V), miniaturization (size 25 cm2), and wireless data communications (Frequency 96 MHz) for wearable applications in e-Health. Its target application is forthe evaluation of fitness of CP during exercises. We use aminiature bi-directional hot-wire sensor for respiratory function,an optical sensor for saturated blood oxygen level or plethsymograph, and two surface electrodes for single lead electrocardiograph. The fitness indexes include blood oxygen level, ECG, and respiratory functions, which will be used for the quantitative evaluation of the level of physical activity. PMID- 17280979 TI - Measurement system for the characterization of the human body as a communication channel at low frequency. AB - Electronic data transfer by capacitive and galvanic coupling through the human body has been proposed by research and industry as a novel but highly promising technology for ultra low power wireless body LANs. Investigation on the most challenging questions considering data communication becomes enabled with a highly versatile measurement system for frequencies in the range of 10 kHz to 1 MHz. The human body is characterized as a transmission medium for electrical current by means of measurements and is investigated as communication channel for biomedical parameter monitoring by using different modulation schemes at low frequency. Excellent transmission was achieved on the thorax while the attenuation increases along the extremities. The injected current is 10 times below the maximum allowed contact current and more than 25 times below nerve stimulation. The new technology has shown its feasibility in clinical trials. PMID- 17280980 TI - Development of an Intelligent PDA-based Wearable Digital Phonocardiograph. AB - Last year at the EMBC 2004 in San Francisco, we presented a paper entitled: "Digital Phonocardiography: a PDA-based Approach", which introduced the development of a PDA-based biomedical instrument capable of acquiring, processing, and analysis of heart sounds. In this paper we present a system, which is not only able to record and display the heart sounds in a Pocket PC but also apply several signal processing and statistical techniques to segment the these signals into four parts (the first heart sound, the systole, the second heart sound and the diastole) and implement feature extraction methods for classification purposes. Classification has been achieved using a Multilayer Perceptron (MLP) Artificial Neural Network (ANN). The system was used to classify a number of normal and abnormal heart sounds (normal, aortic regurgitation, aortic stenosis, mitral regurgitation and mitral stenosis) and validate the effectiveness of the statistical segmentation and the feature extraction methods in this environment. PMID- 17280981 TI - Recoverability trend of blood pressure and pulse transit time after treadmill exercise. AB - This study examines the recoverability trend of blood pressure (BP) and pulse transit time (PTT) during the 60 minutes immediately following a treadmill exercise. Experiments were conducted on 12 healthy and normotensive subjects, including 8 males and 4 females. All subjects were directed to run on a treadmill at 10 kph for 4 minutes. BP was measured at the finger by the Finometer and also at brachial arteries by a sphygmomanometer. PTT was determined as the time interval between the peak of the R wave of electrocardiogram and the foot of photoplethysmogram. Immediate post exercise PTT is significantly lower than its preexercise baseline level (p < 0.001). During the recovery period, PTT initially increases to the original level at 9 minutes after exercise and then increases continuously, peaks at 20 minutes after exercise, and returns to the baseline at 60 minutes. Although PTT is temporarily higher than the baseline during the recovery period, the changes are not significant (p = 0.37). Immediately after exercise, both finger BP and brachial BP are significantly different from pre exercise baseline. There is no significant difference in brachial BP by 5 minutes after exercise and in finger BP, by 9 minutes. PMID- 17280982 TI - Analysis of orientation error of triaxial accelerometers on the assessment of energy expenditure. AB - This paper investigates the effects of orientation error in the positioning of triaxial accelerometers on the assessment of energy expenditure. Four subjects walked on a treadmill at varying velocities ranging from 4km.h-1to 5km.h-1. During each test, a triaxial accelerometer attached to the lower back at arbitrary orientations to record body accelerations. Energy expenditure was estimated by the sum of the integrals of the absolute value of accelerometer output from all the three measurement directions. Based on theoretical analysis and experimental observations, it is concluded that small orientation errors (< 3°) have no distinguishable effects on the estimation of energy expenditure. We propose an efficient method to compensate for larger orientation errors. The experimental results verified the effectiveness of this proposed compensation method. PMID- 17280983 TI - Frequency dependence of phase shift in edema: a theoretical study with magnetic induction. AB - A spectroscopic distribution of induction phase shift as a function of relative volume of edema in the brain, lung and muscle was produced from available tissue data and a simple mathematical model of electromagnetic induction in tissue. The results show that the phase shift is sensitive to the relative volume of edema at frequencies higher than approximately 10 MHz. The behaviors of brain, lung and muscle tissues are substantially different from each other. Increasing the volume of tissue has the effect of lowering the frequency at which the phase shift becomes sensitive to the volume of edema. The results indicate that induction measurement of the phase shift has the potential for becoming a robust means for non-contact detection of edema in brain, lung and muscle tissues. PMID- 17280984 TI - The effect of local cold exposure on pulse transit time. AB - Pulse transit time (PTT) has attracted great interest for developing continuous and noninvasive blood pressure (BP) monitoring devices. This study investigated the effect of finger cold exposure on PTT. 13 healthy and normotensive subjects, including 6 males and 7 females took part in the experiment. Cold exposure was performed by asking subjects to immerse one finger into cold water (9±2°C) for 2 minutes. The photoplethysmographic (PPG) signals were recorded from the cooled and adjacent non-cooled finger simultaneously. PTT was measured between the R-wave of the electrocardiogram (ECG) and a fiducial point in finger PPG pulse for each heartbeat. Three definitions of PTT were investigated and the difference of PTT between two fingers was calculated for each subject. By comparing the difference before and after cold exposure, it was found that local cold exposure had little effect on PTT1, which terminates at the foot of the PPG pulse; however, it affected the PTT3, which terminates at the peak of the PPG pulse. The results suggest that the measurement of PTT which terminates at the foot of the PPG pulse is reliable, while those measurements which terminate at the peak of the PPG pulse or other fiducial points nearby are subject to the effect of local cold exposure and can possibly affect the accuracy of PTT-based applications. PMID- 17280985 TI - Estimation of walking energy expenditure by using support vector regression. AB - This paper develops a new predictor of walking energy expenditure from wireless measurements of body movements using triaxial accelerometers. Reliable data were collected from repeated walking experiments in different conditions on a treadmill with simultaneous measurement of expired oxygen and carbon dioxide. Support vector regression, a powerful non-linear regression method, was used to process and model the data. This novel processing method sets this investigation apart from existing papers. Good results were achieved in the robust estimation of walking related energy expenditure from a number of variables derived from triaxial accelerometer and treadmill speed. PMID- 17280986 TI - Cable-Free Body Area Network using Conductive Fabric Sheets for Advanced Human Robot Interaction. AB - Wearable sensing networks offer a multitude of benefits for the user. One field that can benefit from such technologies is in-home robotics. Much work has been dedicated to the general area of interaction between robots and humans, and more specifically to gesture recognition. We propose a wearable monitoring network composed of conductive fabrics that can more easily facilitate robot interaction. It creates additional interaction by visual indication, and electronically by way of a local PC. This system creates a more natural human-robot interface and makes feasible many new forms of gesture recognition. Finally, we can address safety concerns; the garment gives us a method of locating the human and minimizing the possibility for robots to strike the user. In this paper, we lay out the architecture for such a system, and perform some of the initial characterization. PMID- 17280987 TI - Development of a Portable Acceleration Monitor Device and its clinical application for the Quantitative Gait Assessment of the Elderly. AB - In this study, a handy gait assessment system with a tri-axial accelerometer has been developed and its application for a quantitative assessment of gait in the elderly was examined. This assessment system consists of a portable acceleration monitor device and PC analysis software. This portable device was fixed to the lower front of the subject, and the subject was asked to walk around a test course at a voluntary speed. The activities performed on the test course include standing up, normal walking, fast walking, and walking over a barrier. Gaits in 402 elderly people were measured three times every three months. These subjects were under nursing health services, such as expert place nursing, walking training, power rehabilitation, fall prevention training, and pool training. The measured acceleration was converted into relative velocity and relative displacement of the center of gravity of the subject. Four evaluation indices, i.e., physical activity, stability, symmetry, and average speed were calculated. The results reveal that both the physical activity and average speed decreased after six months under nursing services. PMID- 17280988 TI - Nonverbal communication tool for children with severe motor and intellectual disabilities using biochemical measurement. AB - Children with severe motor and intellectual disabilities (SMID) find it almost impossible to communicate whether they are feeling comfortable or uncomfortable. Most of the children with SMID rely on medical care involving disposable-type life support devices such as tracheostomy tubes or gastric tubes. It is believed that the insertion and removal of these medical devices could cause extreme physical pain under certain circumstances. The authors have previously reported a hand-held type salivary amylase (AMY) activity monitor that can be used to evaluate the sympathetic nervous system. This report proposes a nonverbal communication procedure based on a biochemical measurement using AMY activity for children with SMID. The physiological conditions of these children were evaluated using a hand-held type AMY activity monitor that we fabricated. The AMY activity and heart rate of six subjects, who required daily insertion and removal of tracheostomy tubes or gastric tubes, were simultaneously measured before and after medical care. Apart from one subject who required a respirator due to severe cerebral palsy, the experimental results showed that the AMY value increased sharply by 200 400% after medical care compared to the resting state. Furthermore, the rate of change of AMY activity was 10 times larger than the change in heart rate. Therefore, it is suggested that using these biochemical measurements a nonverbal communication tool for children with SMID can be established. PMID- 17280989 TI - Measuring continuous real-world upper-limb activity. AB - The Strathclyde Upper-Limb Activity Monitor (SULAM) was used to assess real-world upper-limb activity. The SULAM consists of an electro-hydraulic activity-sensor which measures the vertical displacement of the wrist in relation to the shoulder. The aims of this study were to obtain a profile of upper-limb activity in two different populations (able-bodied participants and stroke patients) Ten able-bodied volunteers and ten stroke patients-wore the SULAM while performing their everyday activities. The outcome measures were movement time, its distribution in five vertical ranges, bimanual and unimanual movement time. There was a difference in the use of both upper-limbs for both groups, favouring the dominant/unaffected arm. This difference was only in two of the five ranges (chest to shoulder and shoulder to head for able-bodied participants; waist to chest and chest to shoulder for stroke patients). Bimanual movement was greater than unimanual movement for able-bodied participants whereas unimanual movement was greater than bimanual movement for stroke patients. PMID- 17280990 TI - Detecting seizure onset in the ambulatory setting: demonstrating feasibility. AB - Ambulatory EEG recorders are commercially available. The majority of these recorders are only capable of capturing and storing EEG for later review by clinicians. A few models are equipped with real-time seizure event detectors, but these detectors make no guarantees on when during a seizure a detection is made. This renders current ambulatory EEG recorders unsuitable for activating alarms or initiating therapies to acutely impact seizure progression in the ambulatory setting. Integrating seizure onset detectors into existing ambulatory recorders will make these applications feasible. Successful integration requires that these detectors be executable on the resource-limited digital signal processors found within ambulatory recorders. In this paper we describe the integration of a patient-specific seizure onset detector with a commercially available ambulatory EEG recorder, and demonstrate how such integration could enable the detection of seizure onset in the ambulatory setting. PMID- 17280991 TI - Wearable sensors for reliable fall detection. AB - Unintentional falls are a common cause of severe injury in the elderly population. By introducing small, non-invasive sensor motes in conjunction with a wireless network, the Ivy Project aims to provide a path towards more independent living for the elderly. Using a small device worn on the waist and a network of fixed motes in the home environment, we can detect the occurrence of a fall and the location of the victim. Low-cost and low-power MEMS accelerometers are used to detect the fall while RF signal strength is used to locate the person. PMID- 17280992 TI - Continuous measurement of systolic blood pressure using the PTT and other parameters. AB - In this paper, we proposed the regression model which could estimate unspecified people's systolic blood pressure (SBP) conveniently and continuously and checked its accuracy through clinical experiments. The method for estimating each individual SBP by using only pulse transit time (PTT) has been studied, but it is difficult to estimate unspecified people's SBP with the method using only PTT. Thus we researched several physical characteristic parameters which might affect blood pressure (BP) with the standard that we can measure them easily and conveniently, chose valid physical characteristic parameters through a clinical testing and correlation analysis, and made the regression model using PTT and valid physical characteristic parameters for estimating unspecified people's SBP. Comparing the result of the proposed method with American National Standards Institute of the Association of the Advancement of Medical Instrument (ANSI/AAMI), we know that the proposed regression model gives an acceptable result. PMID- 17280993 TI - Infrared image to evaluate the selective (directional) freezing due to localized injection of thermally important solutions. AB - Cryosurgery is a minimally invasive surgical technique that employs the destructive effect of freezing to eradicate benign or malignant tumors which are difficult or even impossible to be extirpated by conventional surgery. Recently, we proposed a method for flexibly controlling the freezing scale during cryosurgery by percutaneously injecting thermally important functional solutions into the target tissues. This method can also help modify the direction of the iceball formation which is desirable for a successful cryosurgery for treating tumors with complex anatomical structure. To evaluate the effect of controlling the size, shape and direction of the iceball formation by injecting solutions with specific thermal properties into the target tissues, a medical infrared thermometer was introduced in this paper to map the temperature profile over the whole surface above the treated area. The cryosurgical procedure was performed using a minimally invasive cryoprobe cooled by liquid nitrogen in order to obtain a deep regional freezing. Meanwhile, one thermocouple was also amounted in the tip of the probe to record the transient temperature in order to detect the freezing and thawing effect on the tissues. The obtained infrared image was applied to monitor and evaluate the whole process. Simulation experiments on biological tissues (fresh pork and liver) were performed in vitro and four different liquids were injected into the test materials, which were distilled water, an aqueous suspension of aluminum nano-particles in water, ethanol and a 10% solution of the cryoprotective agent dimethylsulfoxide, (Me2SO), respectively. It was clearly demonstrated that the localized injection of an appropriate solution could effectively regulate the tumor-killing area via directional freezing. The study also suggested that infrared imaging can be used as an effective way to monitor and evaluate the selective freezing process, which will provide important information to help enhance fr- eezing damage to the target diseased tissues while preserving the normal tissues from injury. PMID- 17280994 TI - Heart rate variability analysis using electric fabric in dry-normal condition. AB - Significance verification of electric fabric compared with existing electrode is very useful for the wearable and ubiquitous healthcare. In this paper, we verified the significance between Ag/AgCl electrode and electric fabric in dry normal condition through heart rate variability analysis. We can find 98 % or more similarity about low frequency and high frequency parameter which is important for the heart rate variability analysis between two different electrodes in experiment. From this result, we confirmed that the power spectral density of low frequency, high frequency component from the electric fabric has high similarity compared with the result of heart rate variability from Ag/AgCl electrode in dry-normal condition. PMID- 17280995 TI - Novel design for a wearable, rapidly deployable, wireless noninvasive triage sensor. AB - This paper presents a unique design for a low-power, continuous non-invasive sensor capable of remotely monitoring the five major vital signs of a patient. In particular, the sensor is designed for rapid attachment to the fingerbase of a patient by utilizing a clip-type mechanism and is comprised of a photoplethysmograph (PPG), a MEMS accelerometer, a temperature sensor, and a wireless node. Although hastily placed by a medic, the finger sensor will automatically find the location of a digital artery and acquire a clear, pulse signal: a micro-sensor array accommodates the location of the sensor attachment. Additionally, the PPG signal, although corrupted with the patient's motion in chaotic environment, will be recovered by using the MEMS accelerometer and an Active Noise Cancellation algorithm. PMID- 17280996 TI - Active motion artifact reduction for wearable sensors using laguerre expansion and signal separation. AB - This paper presents an active noise cancellation technique that utilizes an accelerometry measurement to recover corrupted wearable health monitoring signals. The technique presented here requires no calibration for each patient and is computationally efficient. Also, a method of determining when the desired signal is correlated with the motion reference is presented with a means of partial signal recovery. The Laguerre basis function provides robustness against calibration as well as improvement in computational efficiency, and symmetric decorrelation accommodates the management of correlated signals. Experimentation shows that the system can produce up to an 85% reduction in wearable sensor error for accelerations up to 2G. PMID- 17280997 TI - Blood pressure measurement using finger cuff. AB - Many research groups have studied blood pressure measurement in finger artery because of its convenience. But, low accuracy prohibits many hypertension patients from using this device. So, we suggest measurement algorithm that measure systolic and diastolic blood pressure in finger artery. And we also develop calibration method that decreases the error from difference of finger circumference by subjects. We apply our methods for 90 subjects (age form 20 to 49, 55 male, 35 female) to test feasibility of our method by AAMI SP10 standard. The mean difference of our system is ±4.7mmHg for systolic pressure, ±4.2mmHg for systolic pressure. It proved that the feasibility of our method is clinically acceptable.(under ±5mmHg). PMID- 17280998 TI - A Preliminary Study for Unconstrained Pulse Arrival Time (PAT) Measurement on a Chair. AB - A method of measuring the pulse arrival time (PAT) non-consciously on a chair is proposed. In this method, the electrically non-contact ECG measurement system and the air cushion with balancing tubes are used. In this paper, the correlation between the typical PAT and the unconstrained PATs (A-PATs) are compared. The typical PAT is measured as the difference of R-peak of ECG and the steepest descent point of the PPG in toe. The three different A-PATs were measured from the pressure pulse of the air cushion (APP). The correlation between the typical PAT and the A-PAT from the steepest descent point of the APP was the highest (R=0.9663). PMID- 17280999 TI - Unconstrained pulse transit time measurement system for computer users. AB - Pulse Transit Time (PTT) is a simple non-invasive method to evaluate vascular function using photoplethysmography(PPG) and electrocardiography(ECG). This study introduces unconstrained PTT measurement method for computer users and evaluates that. The proposed system consists of chair and mouse those can measure ECG and PPG respectability. PTT was defined as time delay between ECG R peak and PPG steepest point. The correlation coefficient between PTT that measured from this system and conventional PTT was 0.93. This work will provide many opportunities for ubiquitous health monitoring. PMID- 17281000 TI - Noninvasive estimation of blood pressure using photoplethysmographic signals in the period domain. AB - In order to detect hypertension at its early stage, blood pressure (BP) of an individual must be carefully monitored. Aiming to monitor BP noninvasively and continuously, this study examines a new feature, normalized harmonic area (NHA), which is extracted from photoplethysmoographic (PPG) signals in the period domain by using the discrete period transform (DPT). BP, pulse transit time (PTT), diastolic time (DT) and NHA were obtained from photoplethysmographic (PPG) signals in the period domain by using the discrete period transform (DPT). BP, pulse transit time (PTI), diastolic time (DT) and NHA were obtained from 28 subjects before and immediately after step-climbing exercise. It was found that NHA has more significant correlation wiith BP than PTT and DT in this study. The mean difference and standard deviation (Mean±SD) between the BP estimated from NHA and the reference BP obtained from a commercial oscillometric BP meter were 0.37±4.3 mmHg and 0.51±4.8 mmHg for SBP and DBP, respectively. The result indicate that NHA is potentially a useful indicator of arterial BP. PMID- 17281001 TI - A short study to assess the potential of independent component analysis for motion artifact separation in wearable pulse oximeter signals. AB - Motion artifact reduction and separation become critical when medical sensors are used in wearable monitoring scenarios. Previous research has demonstrated that independent component analysis (ICA) can be applied to pulse oximeter signals to separate photoplethysmographic (PPG) data from motion artifacts, ambient light, and other interference in low-motion environments. However, ICA assumes that all source signal component pairs are mutually independent. It is important to assess the statistical independence of the source components in PPG data, especially if ICA is to be applied in ambulatory monitoring environments, where motion artifacts can have a substantial effect on the quality of data received from light-based sensors. This paper addresses the statistical relationship between motion artifacts and PPG data by calculating the correlation coefficients between arterial volume variations and motion over a range of stationary to high-motion conditions. Analyses indicate that motion significantly affects arterial flow, so care must be taken when applying ICA to light-based sensor data acquired from wearable platforms. PMID- 17281002 TI - Non-Invasive Tool for Coronary Artery Diagnosis Using Signal Characteristic Analysis (CADSCAN®) and Iso-Surface Optimal Membrane-Adherent Compliant (ISOMAC®) Sensors. AB - MedScanSonics Inc. (MS2)'s CADSCAN®and acoustic ISOMAC®sensors combine state-of-the-art non-invasive acoustic sensing and proprietary Wavelet Transform algorithms with fast DSP core hardware to quickly detect and locate coronary arterial stenoses with near-pinpoint accuracy in real-time. PMID- 17281003 TI - Power spectral analysis of recovery sleep of sleep deprivation and hypnotic drug induced sleep. AB - Hypnotic drugs induced sleep is usually different from physiological sleep in restoring body energy. The cause of the differences is not clear. To investigate the differences between these two types of sleep, in this study, hypnotic drug diazepam (DZP) induced sleep was compared with the recovery sleep following sleep deprivation. Power spectral analysis was used to reveal the different EEG features of these two types of sleep. EEGs were recorded in rat occipital cortex with implanted electrodes under three vigilance states of waking, slow wave sleep (SWS) and rapid eye movement (REM) sleep. Spectral powers of the EEG segments were evaluated in sub-bands of delta (0.5 - 4.0 Hz), theta (4.25 - 8.0 Hz), alpha (8.25 - 16.0 Hz), beta (16.25 - 25.0 Hz) and for total frequency range of 0.5 - 25.0 Hz. The data showed that both hypnotic drug DZP and sleep deprivation increased the time of SWS and REM sleep; however, DZP decreased low-frequency activity in SWS sleep, while sleep deprivation increased low-frequency activity in SWS sleep during recovery sleep. The decrease of low-frequency activity in DZP induced SWS sleep could result from the DZP inhibitory effects. The results suggest that increases of sleep evoked by different factors can have different features and the method of power spectral analysis is useful in revealing deep features of different types of sleep. PMID- 17281004 TI - Prevention of Spontaneous Seizure-like Events in Both in-silico and in-vitro Epilepsy Models. AB - In this paper, we apply the small perturbation control strategy for the prevention of seizure-like events (SLEs) characterized as lower dimensional possibly rhythmic (LPR) activities in both the coupled oscillators in-silico model and the in-vitro low magnesium rat hippocampal slice model. Utilizing the wavelet artificial neural network (WANN), state transitions towards SLEs can be predicted. Successful suppression of SLEs was achieved when brief control perturbations were applied to the field coupling portals of the coupled oscillators model and to the mossy fibers via extracellular field stimulating electrode, respectively. PMID- 17281005 TI - The application of imaginary method in EEG forward question of eccentric spheres models. AB - In this paper, we present a novel method to calculate the scalp potential distribution produced by the inside dipoles of the EEG forward question in detail: imaginary method. Using this method, the eccentric spheres models of the head can be simplified to the homocentric spheres model. The scalp potential distribution of the forward question of EEG of the homocentric spheres model can be solved easily. Using the imaginary method, the influence of the inside eccentric sphere can be replaced by some imaginary dipoles, the imaginary surplus single poles and the fractal single poles as well as fractal dipole. For the question in which the centers of the spheres and the position of the dipole are not in the same line, the analytical solution can be obtained, while the conventional method can only give the analytical solution in the case where all the centers of the spheres and the point of the dipole are in the same line. At last, we validate this method through computer simulation. By comparing the results from the imaginary method, the conventional method and the finite element method FEM (Although FEM can give more precise solution, but it cannot give the analytical solution, which is necessary when solve the reverse question.), the validity of this method is proven. PMID- 17281006 TI - Non-linear electroencephalogram dynamics induced by magnetic stimulation. AB - Non-linear electroencephalogram dynamics induced by magnetic stimulation (MS) were demonstrated using the brain potential map (BPM). The early evoked cortical activity was recorded at the right anterior scalp areas after MS of left hand muscle. Then, the activity shifted with time from the right anterior scalp areas to the right posterior scalp areas, to the left anterior scalp areas, to the left posterior scalp areas, respectively. The changes of evoked cortical activities lasted two periods, and during the interval between two periods negative evoked potentials were observed over the scalp. These results could show the spatio temporal pattern in that information of the stimulus encoding could be processed in cortex. PMID- 17281007 TI - Assess the effect of ciliary neurotrophic factor on extracellular level of neuropeptide Y in paraventricular nucleus using microdialysis. AB - In this study we investigated the effect of ciliary neurotrophic factor (CNTF) on dynamic changes in the release of hypothalamic neuropeptide Y (NPY) of freely moving rats using radioimmunoassay-microdialysis procedure. NPY concentrations in paraventricular nucleus (PVN) dialysate rapidly decreased to the lowest point, 47% of basal level (P<0.01), in 30 minutes after intracerebroventricular injection 5μg CNTF, and then increased slowly to 58%, 78% and 85% of basal level respectively at 60, 90 and 120 min (P<0.05). It became no significant difference with basal level at 150 and 180 min. These results suggested CNTF administration could directly down-regulate NPY release from hypothalamic PVN to reduce food intake and PVN was a target of CNTF's anorectic effect. PMID- 17281008 TI - Threshold adaptation for mean value based operant conditioning. AB - Biofeedback and a variety of brain-computer-interface methods imply as very first stages the obtainment of control of selected signals e.g. the related generating psycho-physiological processes. The basic mechanism in the learning phase is the operant conditioning, which represent a complex behavioral method consisting of several components. One of the most important components is the setting and adjustment of thresholds for the triggering of corresponding rewarding options. An adaptive threshold optimization method, for the training based on average values is presented. The procedure is derivated from the sequential test from Wald. The application of the sequential tests in the learning/training process allows a threshold adaptation corresponding to the abilities of the particular person and to the learning success. PMID- 17281009 TI - Chaotic Dynamics in Tracing BAEP and its Application on Investigating Brainstem Malfunction. AB - The purpose of this study is to investigate the chaotic dynamics of tracing (dynamic) brainstem auditory evoked potential (BAEP), then to investigate the brainstem malfunction via dynamic characteristics of tracing BAEP. The radial basis function neural network (RBFNN) technique in combination with the moving window average (MWA) method was employed in order to extract the tracing BAEP from strong noise background. Data of noisy BAEP were collected from the Infantile spasm (IS) group with brainstem malfunction and the tester group respectively. The chaotic dynamics of tracing BAEP were analyzed using phase projection and correlation dimension techniques. The results of this study have demonstrated: (1) there is a much stronger determination in BAEP than in noisy BAEP shown by more deterministic phase projections and lower D2in BAEP; (2) trajectories of BAEP never repeat and the value of correlation dimension is fractal; (3) the phase projection of BAEP for brainstem malfunction group shows more chaotic and has higher D2than those for the tester group. The conclusions of this investigation suggest that BAEP is chaotic not deterministic and there is rich dynamics in BAEP; tracing BAEP is much more useful than noisy BAEP in describing brainstem malfunction because BAEP shows determination corresponding to brainstem function; BAEP in brainstem malfunction has more non-order dynamics than that in the tester. PMID- 17281010 TI - A simulation of the abnormal EEG morphology by the 3-d finite element method. AB - It's usually called the calculation of potentials on the cortex as the forward problem in the nerve system. Nowadays, the viewpoints of the equivalent source being regarded as the electrical activity of an excitable neuron have been widely accepted. In this paper, a novel method is presented to simulate the abnormal EEG morphology such as the spikes with two phases in the 3-D solution space. The abnormal spikes often occur in the epileptic seizure. Here, the abnormal rhythm is regarded as dynamic activity of equivalent currents source and the head as a homogeneous sphere model as well as the solution space. The finite element method (FEM) is utilized with the help of the ANSYS7.0 software. It is concluded that the abnormal spikes are original from the abnormally discharge process in the brain and the interval of the spikes (IS) can be lengthened with the increasing in the concentration of the intracellular Ca2+([Ca2+]i). It can be helpful to understand the mechanism of the abnormal EEG morphology from the microcosmic viewpoints. PMID- 17281011 TI - A Simulation Study of Firing Patterns based on Coupling Effect between Soma and Dendrite. AB - The aim of this study is to investigate how firing patterns of neuron in hippocampus change with coupling effect between soma and dendrite via simulation of single neuron firings by a two-compartment (soma-dendrite) model. The results will help to understand how firing patterns relative to synaptic plasticity in further study. The neuron model used in this study consisted two compartments: the soma compartment and the dendrite compartment, which can describe synaptic input functions. Simulations of neural firings were performed with fourth order Runge-Kutta algorithm with different range of coupling conductance. Firing patterns of neuron were simulated under different current applied to soma (Is). The range for different firing patterns is: Is=0..A/cm2, range for spiking is [0.0, 1.8] and [4.5, ..], for bursting is [1.9,4.4]; Is=0.5..A/cm2, range for spiking is [0.0, 2.2] and [4.0, ..], for bursting is [2.3,3.9]; Is=1.0..A/cm2, range for spiking is [0.0, 2.5] and [3.6, ..], for bursting is [2.6,3.5]; Is=1.5..A/cm2, range for spiking is [0.0, 2.5] and [3.8, ..], for bursting is [2.6,3.7]; Is=2.0..A/cm2, range for spiking is [0.0, 2.6] and [3.6, ..], for bursting is [2.7,3.5]; Is=2.5..A/cm2, range for spiking is [0.0, 2.6] and [3.3, ..], for bursting is [2.7,3.2]. PMID- 17281012 TI - A consideration of the characteristics of ABR on the basis of a differential equation model and the estimation of parameters of its solution. AB - Today ABR ABR: Auditory B ainstem Responses) characteristics are widely and qualitatively used, and they ar e mainly used for clinical application of a consciousness obstacle, brain death and some consciousness level, vegetative state and so on, as the very useful inspection method. Until now, many various characteristics and models about these brain waves have been reported. But the theor ies and experiments of ABR are still more needed to understand the ABR characters in more details. In this paper we discussed the analysis of a differ ential equation model on the latency of the 5th wave of ABR, and considered the system model of generation of the type of solution of the differential equation model on the basis of an estimation of parameters of a solution of its equation model by using the Taylor ser ies method as an iterative approximation method. PMID- 17281013 TI - A new silicon retina model and its advantages. AB - A new model of silicon retina based on the receptive field structure of retinal ganglion cells has been proposed. Unlike previous neuromorphic models, the proposed model directly incorporates into the receptive field model, contribution from both the inner and outer plexiform layer of the retina, as a linear combination of the two. It has been shown that such a system is capable of aiding in the computation of zero-crossing maps, in higher regions of the brain, using a fourth or higher order derivative. This model is likely to have a neuromorphic implication in generating and implementing a simplistic derivative analyzer mimetic of the Human Visual system (HVS) and is also endowed with additional advantages from the perspective of image retrieval. PMID- 17281014 TI - Neuronal dynamics of dynamic synapses. AB - This work presents a model of minimal time-continuous target-cell specific use dependent short-term synaptic plasticity (STP) observed in the pyramidal cells that can account for both short-term depression and facilitation. In general it provides a concise and portable description that is useful for predicting synaptic responses to more complex patterns of simulation, for studies relating to circuit dynamics and for equating dynamic properties across different synaptic pathways between or within preparations. This model allows computation of postsynaptic responses by either facilitation or depression in the synapse thus exhibiting characteristics of dynamic synapses as that found during short-term synaptic plasticity, for any arbitrary pre-synaptic spike train in the presence of realistic background synaptic noise. Thus it allows us to see specific effect of the spike train on a neuronal lattice both small-scale and large-scale, so as to reveal the short-term plastic behavior in neurons. PMID- 17281016 TI - EEG model and location in brain when at excitation. AB - The aim of this study is to confirm the character of EEG and the location in brain when a person is being excited. The subjects get excited with absorption of fixed quantity of coffee. EEG signals are collected with Phoenix Digital EEG with 128 channels, and compared with the ones before the subjects drink the coffee. Obvious differences have been found between them. The character of EEG is a wave crest of 38Hz when the person is excited, and the height is about 200. Then with the software of ASA 3 Course designed by ANT company of Germany, the location in brain is confirmed when a person gets excited. The region of the location in brain when a person is excited is focused in the area of the middle abdomen in the pons'side near to bulbar. PMID- 17281015 TI - Study of a chaotic olfactory neural network model and its applications on pattern classification. AB - Based on the research of biological olfactory system, a novel chaotic neural network model - K set model has been established. This chaotic neural network can not only simulate the real brain activity of olfactory system, but also present novel chaotic concept for signal processing and pattern recognition. This paper investigates the characteristics of the K set models. Experimental result shows that KIII model can be used for various area of pattern classification efficiently. PMID- 17281017 TI - Applying Independent Component Analysis on ECG Cancellation Technique for the Surface Recording of Trunk Electromyography. AB - Surface electromyography (sEMG) recorded from the trunk area may reflect underlying muscular function, and is the current standard for in vivo functional examination. However, sEMG of this area, including the low back musculature, usually encounters substantial interference from strong cardiac signals. It is therefore imperative to remove electrocardiogram (ECG) interference from sEMG data. This paper discusses a denoise method using independent component analysis (ICA) and a high-pass filter to effectively suppress the interference of ECG in sEMG recorded from trunk muscles. The performance of this technique was evaluated with simulation experiments. To compare the outcome of the ICA and filtering technique to the original sEMG signal, correlation coefficients in both time domain waveform and frequency spectrum were computed. In addition, different filter bands were evaluated. The ICA ECG cancellation with a 30Hz high-pass filter showed higher mean correlation coefficients in the time domain (0.97±0.08) and in the frequency spectrum (0.99±0.06) than any other techniques. This suggests that the ICA ECG cancellation technique with a 30 Hz high-pass filter would be the most appropriate method to extract useful sEMG signals from trunk muscles. PMID- 17281018 TI - Current density distribution under surface electrode on posterior tibial nerve electrical stimulation. AB - Electrical stimulation on the posterior tibial nerve is commonly used in the measurement of somatosensory evoked potential (SEP). To improve the efficiency of stimulation, the potential field and current density distributions under the surface electrodes were simulated with a three layer theoretical model. The mirror method was used to analyze the potential field of point charge. Integration of the field and the stimulus area provide the potential field for one surface electric pole. Potential field distribution of the bipolar electrodes was calculated by superimposition of two unipolar fields. Finally, the current density distribution was calculated by Laplace equation. An analytical solution of the potential field was obtained; thereafter the numerical solution of the current density distribution was calculated. The potential field and current density distribution were simulated by 2-D plot. From the model and simulation, the potential and current density distributions were not found to be evenly distributed under transcutaneous stimulation electrode and the maximum current density is located under the poles. The result suggests that bipolar stimulator should be applied axially along the stimulated nerve course. PMID- 17281019 TI - Electrode placement during stimulus evoked electromyographic monitoring of iliosacral screw insertion: a finite element model. AB - Stimulus evoked electromyography is currently used during surgery to prevent nerve root injury during iliosacral screw insertion. In order to evaluate the importance of anode location in this procedure, a three dimensional finite element model was constructed from computed tomography data to evaluate the effectiveness of five electrode locations. Three anode locations (CASIS, dorsal midline and ventral midline) performed well, including the one most commonly used clinically (ventral midline). The dorsal midline, ventral midline, and CASIS anode locations provide data on the proximity to the neural structure in the superior, inferior and contralateral directions respectively that were attenuated at other anode locations. Modification of the technique to include monitoring of multiple anode locations could further reduce the incidence of injury. PMID- 17281020 TI - A study of the phase resetting from pre-stimulus to post-stimulus alpha wave. AB - The alpha wave (8~13 Hz) phase resetting from pre-stimulus to post-stimulus is investigated for eight healthy subjects in a visual and auditory synchronously oddball stimuli experiment. Six parameters are considered: pre-stimulus amplitude and phase angle, post-stimulus amplitude and latency of first positive and negative peak. The results show that the amplitude relationship between pre- and two post-stimulus can be described by a cubic polynomial model; and by using the method of outlying cases test partial phase resetting from pre- to post-stimuli in the band of alpha wave was confirmed in visual and auditory synchronously oddball stimuli experiment. PMID- 17281021 TI - A Computational Model for CMAP and F-wave Signal Generation. AB - Nerve conduction studies (NCS) are often carried out to evaluate patients with peripheral nervous system disorders. NCS instruments with automated waveform analysis capability could expand the accessibility of the NCS to improve overall patient care quality and to reduce health care cost. In this paper, a computer model is described for generating realistic waveforms often measured during NCS. Availability of such computational model will facilitate the rapid development of advanced signal analysis algorithms for intelligent EMG systems. PMID- 17281022 TI - Dynamic-average Characteristics of Late Wave of Auditory Evoked Potentials for Synaptic Malfunction Rat Model. AB - The aim of this study is to investigate dynamic characteristics of late wave of auditory evoked potentials (AEPs) in synaptic malfunction rat model. Two dynamic characteristics relative to cognitive function were investigated which are dynamic latency and dynamic amplitude of P1. Synaptic malfunction model was made by Sprague-Dawley rats via microinjecting beta-amyloid protein (A-beta) into hippocampal CA1 area of rat. Dynamic AEPs with high background noise were recorded for both model and normal rats in experiments. Dynamic late wave were taken from dynamic AEPs using third-order correlation and wavelet technology. The dynamic-average latency and the dynamic-average amplitude of P1 in a small time window (5s) were performed as dynamic index in this study, which remain most of dynamic information because the average window was very small. Then dynamic average latency and the dynamic-average latency of P1 were compared between synaptic malfunction rat and normal group. The results of this study have demonstrated that: (1) the dynamic-average latency of P1 for model rats prolonged remarkably than control (P<0.01, alpha =0.05); (2) the dynamic-average amplitude of P1 for model rats increased remarkably than control(P<0.01,alpha =0.05). The conclusion is that dynamic-average latency and dynamic-average amplitude in the synaptic malfunction rats model has obvious difference with normal group. PMID- 17281023 TI - Selective activation of small nerve fibers for assessing carpal tunnel syndrome. AB - Carpal tunnel syndrome (CTS) diagnosis could be improved by selectively activating the different types of nerve fibers traversing the carpal tunnel. The objective of this study is to assess the potential of an anodal blocking technique using tripolar surface electrodes for achieving selective fiber activation and evaluating the severity of CTS. Simulations were performed using McNeal's model to determine the stimulating and blocking thresholds for different diameter/conduction velocity groups of nerve fibers. At 9.36 mA stimulus amplitude all nerve fibers from 9 mum to 20 mum were activated. When the current amplitude was increased further, large nerve fibers started getting blocked while small nerve fibers remained active. By gradually increasing the current amplitude small nerve fibers can be selectively activated without the activation of large fibers. The severity of CTS generally progresses from large to small nerve fibers, hence by comparing normal values of amplitude and peak latency of different nerve fiber diameter groups to the CTS affected median nerve recordings of the patient, severity of this syndrome could be detected. PMID- 17281024 TI - Changes of Reflex, Non-reflex and Torque Generation Properties of Spastic Ankle Plantar Flexors Induced by Intelligent Stretching. AB - Spasticity, contracture, and muscle weakness are major sources of disability in stroke. Changes of torque-generating capacity as well as reflex and non-reflex properties of ankle plantar flexors induced by strenuous stretching in chronic hemiplegia were investigated. Twelve subjects with a unilateral stroke and 10 healthy controls underwent 30 minutes of strenuous intelligent stretching treatment. Reflex and non-reflex components of spastic hypertonia and force generating capacity of ankle plantar flexors were investigated. Dorsiflexion (DF) range of motion (ROM) was increased (p=0.002) and passive stiffness and passive resistant torque of the spastic muscles were decreased (p=0.004 and 0.007, respectively), while reflex hyper-excitability diminished slightly but with no statistical significance. The maximal voluntary contraction (MVC) torque of the spastic ankle plantar flexors was increased after the forceful stretching treatment (p=0.041). In contrast, the stretching treatment of the healthy plantar flexors did not change any of the variables measured before and after stretching. The stroke subjects who gained more DF ROM or larger decrement of stiffness achieved greater increment of the peak torque generation after the stretching (r=0.597 with p=0.040 and r=-0.746 with p=0.005, respectively). These results suggest that the strenuous dynamic stretching could improve the force-generating capacity of spastic muscles as well as reduce the passive stiffness and increase ROM. PMID- 17281025 TI - Middle latency auditory evoked potential anaesthesia correlates of consciousness: practicality & constraints. AB - The hypothesis of this study is that significant differentiation of consciousness (CO) and unconsciousness (UNCO) is possible, using individual ML+AEP (10-140 msec) latency measures, within the context of a practical routine clinical depth of anaesthesia monitoring device. We have assessed individual latency band measures of the middle-latency auditory evoked potential (ML+AEP) as candidates to measure depth of CO or UNCO amongst a group of anaesthetised surgical patients. We have also compared ML+AEP correlates with conventional auditory evoked potential (AEP) index and bispectral index (BIS). This study investigates amplitude measures, limits and the practicality of using a single EEG channel ML+AEP recording system. ML+AEP amplitude-related correlates were assessed against CO and UNCO events during anaesthesia. ML+AEP measures were computed for each of the following AEP component-related latency time bins (LTB): Na;15 25msec, Pa;25-35 msec, TP41;35-45 msec; Pb/P1; 45-55 msec, N1;80-100 msec, N1;80-140 msec, and ML+AEP;0-140 msec. Twenty patients (aged 28-68 yrs) undergoing day surgery had their electroencephalography (EEG) monitored during binaural auditory stimulus presentation (6.8 clicks per second). The AEP grand mean waveform (AEPgmw) was computed for each consecutive stimulus AEP event, by way of averaging the previous 256 AEPs. The mean and SD amplitude associated with each of the ML+AEP ranges were computed for the whole study period and also for the predetermined events 1 to 13 (CO:1;2;3;12;13 and UNCO:4 11). Results included BIS data, measures derived from the AEPgmw across both the ML+AEP range (0-140 msec), and also individual LTB segments. PMID- 17281026 TI - On-line Detection of Perceptual Signatures in Multichannel ECoG. AB - Neocortical ECoG studies have unveiled the presence of active states - spatial patterns of amplitude modulation- in the beta- gamma ranges in the presence of conditioned stimuli that resemble cinematographic frames. These sequences of active frames emerge with abrupt phase resettings, followed by resynchronization and stabilization over channels, and magnified intensity. An online pattern recognizer that captures the spatial and spectral characteristics of the active frames is presented. The results of detection are confirmed via high occurrences of pragmatic information, defined by the ratio of pattern intensity to pattern stability. PMID- 17281027 TI - An MRI compatible visual force-feedback system for the study of force control mechanics. AB - Motor task experiments play an essential role in exploring the brain mechanisms of movement control, and visual force-feedback is an important factor in these motor experiments. In this paper, the authors proposed a visual forcefeedback system suitable for neuroscience experiment. With this system, the force output produced by participants can be detected and recorded in real time, while force output was visually displayed as a feedback cue to the participants simultaneously. Furthermore, this force feedback system is MRI compatible, and can be used both in fMRI and ERP experiments. The proposed system has been applied in handgrip tasks and finger movement experiments, which were designed to explore the relationship between force output and brain activation mode in normal subject and stroke patient. The results demonstrated that various force levels were well detected and visual feedback signals enabled the accomplishment of experiments with both fixed and variable target force levels. PMID- 17281028 TI - Reduction of the Ballistocardiogram Artifact in Simultaneous EEG-fMRI using ICA. AB - The recording of EEG signals during fMRI scanning is now technically feasible and safe. However, artifacts relating to pulsatile blood flow (the ballistocardiogram) may still be prominently present in EEG data recorded in the MRI magnet. The application of Independent Component Analysis (ICA) in order to reduce these artifacts off-line was investigated in three different types of EEG, one normal Visually Evoked Potential (VEP), one normal ongoing EEG in a normal subject and the EEG of an epilepsy patient showing abnormal transients in the EEG. Results show that ICA is effective in reducing these pulsation artifacts, but that remaining signal quality may be affected. PMID- 17281029 TI - Game motivated and constraint induced therapy in late stroke with FMRI studies pre and post therapy. AB - 20 patients with stroke more than one year earlier were evaluated, admitted to a novel therapy including constraint-induced and computer game-motivated therapy. Statistically significant improvements after 4 weeks of late therapy were seen in all 20 patients on nine out of eleven quantified clinical evaluation scales. The patients looked forward to and enjoyed the therapy. These same late stroke patients were studied via fMRI BOLD immediately before therapy and post therapy. fMRI BOLD studies confirm brain functional reorganization; 3 of the 20 fMRI cases are presented here. We propose that fMRI can help in the process of designing effective stroke therapy programs based on biological principles of brain plasticity. PMID- 17281030 TI - Removing artifacts and background activity in multichannel electroencephalograms by enhancing common activity. AB - Removing artifacts and background EEG from multichannel interictal and ictal EEG has become a major research topic in EEG signal processing in recent years. We applied for this purpose a recently developed subspace-based method for modelling the common dynamics in multichannel signals. When the epileptiform activity is common in the majority of channels and the artifacts appear only in a few channels the proposed method can be used to remove the latter. The performance of the method was tested on simulated data for different noise levels. For high noise levels the method was still able to identify the common dynamics. In addition, the method was applied to a real life EEG recording. Also in this case the muscle artifacts were removed successfully. For both the synthetic data and the analyzed real life data the results were compared with the results obtained with principal component analysis (PCA). In both cases the proposed method performed better than PCA. PMID- 17281031 TI - Real time heart ischemia detection in the smart home care system. AB - In this paper, a novel real-time algorithm for detecting ischemia in the ECG signal is proposed. The goal of this research is to meet the requirements of some smart cardiac home care devices, which can automatically diagnose the ECG and detect the heart risks outside the hospital, especially heart ischemia without symptoms in their early stages. The algorithm is developed based on a real time R peak detector, time domain traditional ECG parameters, the advanced morphologic parameters from Karhunen-Loeve transform, and the adaptive neurofuzzy logic classification. Besides, in order to improve the reliability of our algorithm, several significant constraints of the ECG signal are considered. As a result, the ischemia episodes can be detected if the ischemic alteration persists longer than one minute in the ECG signal. PMID- 17281032 TI - Pervasive computing based multimodal tele-home healthcare system. AB - This paper discusses a pervasive computing based multimodal tele-home healthcare system in terms of a Human-Centered Pervasive Computing System Model. PMID- 17281033 TI - A telemonitoring architecture to support chronic disease management and acute episode monitoring. AB - We describe a telemonitoring architecture designed to support the dual role of chronic disease management and acute episode monitoring. In the former, measurements of parameters such as weight and blood pressure are taken periodically and are used to determine a change in the condition of a patient and thus prompt intervention in therapy. However, such patients can deteriorate rapidly and enter a phase where constant monitoring of vital signs is required. In these conditions, our system monitors ECG, SpO2and temperature continuously and transmits data on preset events or at preset times. To date such monitoring has required two systems; we have developed a single system to fulfil both roles. Transmission and control protocol are designed along principles of the 11073 standard. We show how such monitoring can manage patients with acute conditions such as unstable angina and heart failure. PMID- 17281034 TI - Evaluation of the web-based care-requiring client and Home Helper support system. AB - In Japan, Home Helpers are employed by hospitals, care companies or the welfare office, and are sent to homes of elderly persons to provide home welfare and care services. The care items for one month are scheduled by the care manager; however, the care items are often changed by request from the client, and the Home Helpers need to know these changes as soon as possible. The web-based care requiring client and Home Helper support system is employing for improvement of the problem. In this study, we have evaluated the data entry time, the operation of choosing the items, the legibility of buttons displayed on the LCD, and the comprehensibility of displayed care item buttons. The evaluation found the data entry to be an easy operation. PMID- 17281036 TI - Personal digital exercise trainer for managing, monitoring and recording the exercise. AB - We developed a portable digital exercise trainer device which manages, monitors and records the user's physical status and workout during exercise session. It guides the user in doing efficient exercise to reach specific fitness goals. It keeps the full exercise program i.e. exercises start date and time, duration, mode, control parameter, intensity in its memory which helps the user in managing his exercise. Exercise program can be downloaded from the internet. During exercise it continuously monitors the user's physiological parameters: heart rate, number of steps walked, and energy consumed. If these parameters do not range within prescribed target zone, the device will alarm the user as a feedback to control exercise. The device displays these parameters on graphic LCD. During exercise it continuously records the heart rate and number of steps walked every 10 seconds along with exercise date and time. This stored information can be used as treatment for the user by an exercise expert. Real-time ECG monitoring can be viewed wirelessly on a remote PC. PMID- 17281035 TI - Wireless system for real-time recording of heart rate variability for home nursing. AB - Modern wireless communication technologies offer new possibilities for patient monitoring in hospitals, as well as at home or in outdoor environments. In this paper, we present a wireless system for ECG recordings and real-time analysis of heart rate variability (HRV). The system also makes it possible for distance consultation, for example with a specialist in cardiology, with the help of a WEB solution. PMID- 17281037 TI - A simple system for telemonitoring the daily life of an aged person living alone. AB - A simple system for telemonitoring the daily life of an aged person living alone was developed. The system consists of a current sensor and a pair of computers. The sensor detects changes in the power line current of electrical appliances. The computer at the aged person's end transfers the output signal of the sensor every minute to the computer at the family end via the Internet. In this preliminary study, three days trial was conducted, and changes in the output signal of the sensor were monitored without any trouble. If this system is used, a family may be able to estimate a parent's living condition inexpensively and in real time. PMID- 17281038 TI - An Internet-based Tele-homecare System with Trinomial Protocol. AB - Since the population-aging problem is increasingly affecting the society, health monitoring at home with interactive teleoperation is of interest to researchers and healthcare practitioners. Thus, we develop a low-cost and platform independent telecare system to support the aged and disable people for long-term health care online monitoring. A trinomial protocol and multi-modal human-machine interfaces are designed to decrease the influence of time delay in human interface of teleoperation and give the operator a robust and safe control of the robot. Experimental results show that the system can provide stable and reliable homecare service between physicians, nurses and patients. PMID- 17281039 TI - Development of an Exercise Meter using Triaxial Acceleration Data. AB - Shinshu University and an NPO "JTRC" (Jukunen Taiiku Daigaku Research Center; a health promotion and support organization) provide exercise guidance focused on walking activity with the object of enhancing strength among elderly individuals. Sanyo Electric has developed an exercise meter as a tool to promote these efforts effectively. This exercise meter is equipped with a function providing estimates of energy consumption, leg muscle strength, and endurance based on triaxial acceleration data from the lumbar region. In this paper, we provide an outline of the estimation techniques and present an application of this exercise meter. PMID- 17281040 TI - 3D Imaging System for Visualizing and Monitoring Patients. AB - Three-dimensional (3D) visualization or 3D monitoring of patients or infected animals is useful in actual clinical environment. We propose a 3D imaging system with a single camera and multiple mirrors. The camera is located directly above the object and the multiple mirrors are placed surrounding the object. The single captured image includes multiple viewpoint images: the object captured directly and the same objects reflected by the mirrors. After a simple calibration of the measurement, the 3D volume data are reconstructed with the visual hull based method. Texture mapping is also performed to enhance the reality. A living object was observed in usual environment using this system. The results have demonstrated effectiveness of the system. PMID- 17281041 TI - Webcam mouse using face and eye tracking in various illumination environments. AB - Nowadays, due to enhancement of computer performance and popular usage of webcam devices, it has become possible to acquire users' gestures for the human-computer interface with PC via webcam. However, the effects of illumination variation would dramatically decrease the stability and accuracy of skin-based face tracking system; especially for a notebook or portable platform. In this study we present an effective illumination recognition technique, combining K-Nearest Neighbor classifier and adaptive skin model, to realize the real-time tracking system. We have demonstrated that the accuracy of face detection based on the KNN classifier is higher than 92% in various illumination environments. In real-time implementation, the system successfully tracks user face and eyes features at 15 fps under standard notebook platforms. Although KNN classifier only initiates five environments at preliminary stage, the system permits users to define and add their favorite environments to KNN for computer access. Eventually, based on this efficient tracking algorithm, we have developed a "Webcam Mouse" system to control the PC cursor using face and eye tracking. Preliminary studies in "point and click" style PC web games also shows promising applications in consumer electronic markets in the future. PMID- 17281042 TI - An Integrated System for Body Shape Analysis and Physical Fitness Test -HIMS. AB - Exercise has been proven to be very helpful for maintaining and promoting human health. However, recent research showed that too much or inappropriate exercise may hurt human health. In order to maintain and promote human health, appropriate amount of exercise should be performed according to physical condition and appropriate exercise prescription. This paper proposes an integrated system for body shape analysis (BSA) and physical fitness test (PFT) -HIMS, which consists of 5 data acquisition modules for analyzing physiological status, an exercise load control module, a data processing module and a main control module. The data acquisition modules are integrated to carry out the tests required for exercise prescription in a systematic way. The parameters obtained from the tests include cardio-respiratory endurance, muscle strength, muscle endurance, agility, power, blood pressure at rest, blood pressure at recovery, body fat and body weight. So we can measure 7 kinds of parameters fast and conveniently on one system. PMID- 17281044 TI - PDA based Point-of-care Personal Diabetes Management System. AB - Diabetes is an incurable chronic disease with the prevalence high in developed countries. The number of patients in Korea is also on a steady increase. Patients have to self-manage their blood glucose level by daily test and insulin injection. Therefore, it is very important to assist them in self-management procedure. In this study, PDA(personal digital assistant) based PDMS (personal diabetes management system) was developed in the integrated environment of Visual Studio .NET 2003, which consisted of four main menus to manage personal information, diet, exercise, and blood glucose. It gives quantitative health indices, such as BMI (body mass index) and diabetes index, based on personal physical information, pedigree, and living habits. In addition, it is capable of predicting change of the body weight, which may remind patients of the importance of the disease management. The present system can be used as a mobile device within the tele-healthcare system integrated with medical center through Internet. PMID- 17281043 TI - A multimedia telemedicine system. AB - A multimedia telemedicine system (MTS) using Transfer Control Protocol and Internet Protocol (TCP/IP) over the Internet is developed. Doctor with patient and doctor can communicate each other using this system. Real-time data, including audio, video and instant message (IM), and non-real-time data, including vital sign signals, radiological images with DICOM 3.0, file, bio signal, bio-data and so on, can be exchanged on the system. This system's architecture is client/server mode. All data are encoded/compressed before transferring through Internet/Intranet. The real-time audio is encoded and decoded by MPEG (Moving Picture Experts Group) audio layer 3 algorithm and real time video is encoded and decoded by MPEG-4. The software implementation of needed functionality without any externally attached hardware CODEC (Coder/Decoder) units enables the compact design with low cost. The real-time video has 25 frames per second at Local Area Network (LAN) and more than 20 frames per second at ADSL. PMID- 17281045 TI - Personal recognition rate improvement using head-top image and an application to walking subject. AB - A personal identification method using head-top image is improved for the smart house. The personal recognition rate was 86.4 percent in the previous report from eleven subjects who stood still. It was improved to 100 percent in this study by using the same image database of the previous report. Moreover, head-top image sequences were acquired when the subjects under the thermo camera started walking, and the personal recognition rate was 52 percent from six subjects. PMID- 17281046 TI - Inspiring computer mouse. AB - Inspiring product is a kind of product that enhancing the existing product with a close-loop system to detect the user's health and to inspire the body in a beneficial way. The bio-signals of the user are being measured and the body is stimulated while the traditional functions of the product are used. An inspiring computer mouse prototype is specialized in this paper as an example of inspiring product to further explain the spirits of inspiring product. With an additional circuit board inside the mouse, addition to the common functions of a computer mouse, the inspiring mouse can detect user's bio-parameters such as pulse wave, heart rate, blood oxygen saturation etc., and emit infrared light to stimulate and improve user's microcirculation imperceptibly as well. A coupled infrared LED and photodiode that was used for detecting pulse wave, a processor system ADuC845 were adopted in the circuit. Pulse wave was transferred into computer via RS-232 with an additional cable along with the common mouse's cord, and analyzed by the analysis software running backgroundly to elicit valuable information. Also the perspective about other inspiring products was discussed. PMID- 17281047 TI - Reversible Watermarking Surviving JPEG Compression. AB - This paper will discuss the properties of watermarking medical images. We will also discuss the possibility of such images being compressed by JPEG and give an overview of JPEG compression. We will then propose a watermarking scheme that is reversible and robust to JPEG compression. The purpose is to verify the integrity and authenticity of medical images. We used 800x600x8 bits ultrasound (US) images in our experiment. SHA-256 of the image is then embedded in the Least significant bits (LSB) of an 8x8 block in the Region of Non Interest (RONI). The image is then compressed using JPEG and decompressed using Photoshop 6.0. If the image has not been altered, the watermark extracted will match the hash (SHA256) of the original image. The result shown that the embedded watermark is robust to JPEG compression up to image quality 60 (~91% compressed). PMID- 17281048 TI - Implementing of SPIHT and Sub-band Energy Compression (SEC) Method on Two Dimensional ECG Compression: A Novel Approach. AB - In this paper, a novel ECG data compression method is presented which employs set partitioning in hierarchical trees algorithm (SPIHT), sub-band energy compression (SEC) method and two-dimensional electrocardiogram (2D-ECG). The 2D-ECG is a two dimensioned array, which each row of this array indicates one or more period and amplitude normalized (PANed) ECG beats. In the previous works, SPIHT and sub-band energy compression method have used to compress one or two-dimensional signals separately and have shown their efficiencies such as precise rate control, progressive quality, high compression ratio and low root mean square difference (PRD). In here, we put these two methods together and illustrate that they can be applied to 2D-ECG to achieve better results and this is because of the wavelet transform eliminating effect on redundancies between adjacent samples - it is also eliminated in one-dimensional ECG - and between adjacent beats by applying 2D wavelet transform. PMID- 17281049 TI - A Web-based Wavelet Application to Reduce One Dimensional Physiological Data with Infrequent Short Duration Event for Remote Display. AB - Most current patient monitors can connect to a local area network. This has resulted in an exponential increase in the data volume to be stored, transmitted and viewed. A novel Web-based wavelet application to perform reliable display of long-term one dimensional (ID) physiological data with infrequent short duration events on the client through lossless transfer of only the useful data is proposed. Our solution, in which only the scaling coefficients are transmitted, is able to analyze, transfer and display data efficiently. More importantly, it adapts data to the display width of the remote monitor screen by adjusting the resolution through decomposition, so that segments of physiological interest can be extracted and transmitted at the required resolution. This not only accelerates data transfer but also provides a less cluttered display. This also contributes to an important aspect of telemedicine applications that has received little attention, that is the integrity and reliability of data interpretation and diagnosis. PMID- 17281050 TI - Comparison of JPEG 2000 and Other Lossless Compression Schemes for Digital Mammograms. AB - In this study, we propose JPEG 2000 as an algorithm for the compression of digital mammograms and the proposed work is the first real-time implementation of JPEG 2000 on a mammogram image database. Only the lossless compression mode of JPEG 2000 was examined to ensure that the mammogram is delivered without distortion. The performance of JPEG 2000 was compared against several other lossless coders: JPEG-LS, lossless-JPEG, adaptive Huffman, arithmetic with a zero order and a first order probability model and Lempel-Ziv Welch (LZW) with 12 and 15 bit dictionaries. Each compressor was supplied the identical set of 50 mammograms, each having a resolution of 8bits/pixel and dimensions of 1024 × 1024. Experimental results indicate JPEG 2000 and JPEG-LS provide comparable compression performance since their compression ratios differed by 0.72% and both compressors also superseded the results of the other coders. Although JPEG 2000 suffered from a slightly longer encoding and decoding delay than JPEG-LS (0.8s on average), it is still preferred for mammogram images due to the wide variety of features that aid in reliable image transmission, provide an efficient mechanism for remote access to digital libraries and contribute to fast database access. PMID- 17281051 TI - Performance Evaluation of JPEG 2000 for Specialized Electronic Patient Record Exchanges. AB - Distant diagnostic services require the exchange of medical images and medical data in the form of specialized patient records. Given that multiple images for one patient are often used by these services, considerable demands are placed on support applications implementation, because of the processing and transmission infrastructure limitations found on isolated rural areas. This work proposes to evaluate the performance of medical image compression for such constrained scenario, based on the JPEG 2000 compression standard, in order to improve distant diagnostic services usability. Separate groups of 1 to 15 high resolution gray scale and color cytology images of fixed dimensions were compressed in one file, applying different possible bitrates, tile size and code-block size, for six discrete wavelet decomposition levels. Experimental results show that the adjustment of these parameters, allows compressing the worst data load case (135 MB with moderate lossy compression) in around two minutes, on an average current PC. PMID- 17281052 TI - Medical Image Compression using Wavelet Transform on Mobile Devices with ROI coding support. AB - Medical applications have already been integrated into mobile devices (e.g. Tablet PC's and PDA's) and are being used by medical personnel in treatment centers, for retrieving and examining patient data and medical images. Network transmission and image data processing are key issues in such platforms, due to the significant image file sizes. Wavelet transform has been considered to be a highly efficient technique of image compression resulting in both lossless and lossy compressed images of great accuracy, enabling its use on medical images. This paper discusses a Picture Archiving and Communication Systems (PACS) application designed for viewing DICOM compliant medical images using Wavelet compression with ROI coding support, on mobile devices. In addition, it presents initial results from its pilot application and demonstrates its performance over heterogeneous radio network segments, like IEEE 802.11b, GPRS and DVB-H. PMID- 17281053 TI - Region of interest image coding for digital mammography. AB - In this paper, we investigate region-based wavelet compression methods and describe a region-based coder based on the Set Partitioning in Hierarchical Trees (SPIHT) algorithm, called unbalanced spatial orientation trees (UBT), applied to digital mammograms. We compare this method against the region-based extension of SPIHT (ROI-SPIHT), and the ROI coding unit of JPEG2000 (JP2K) algorithm on five digital mammograms compressed at rates ranging from 0.1 to 1.0 bits per pixel (bpp). We show that UBT is competitive in PSNR with the other two region-based coding methods, also providing a more general multiregion multiquality coding framework rather than ROI/non-ROI coding. Unlike ROI-SPIHT, UBT allows encoding of diagnostically significant regions with best possible fidelity while allocating less number of bits to remaining regions. PMID- 17281054 TI - Development of flexible self adhesive patch for professional heat stress monitoring service. AB - Too much exposure in a very hot environment can cause heat stress which leads to the fatal heat stroke. To prevent heat stress related diseases, flexible self adhesive patch for professional heat stress monitoring service has been developed. By using flexible printed circuit board (PCB) and silicone based packaging, high level of robustness and ease of usage has been accomplished. This patch can be repeatedly attached to the chest of the user with comfort. And it can stand the sweat and be washed with water to reuse. For this patch is small in size (9 cm triangle shape) and light in weight (55g), it can be used in the most demanding situation. To analyze the heat stress of user, it records 1 lead electrocardiogram, body temperature, humidity and 2-axis acceleration. It's Bluetoothtrade communication module can connect various terminal device according to the configuration. With the body weight input by user and 3 week work log it can estimate user work load, acclimatization, total amount of work done, wet bulb globe temperature (WBGT) index, which is the screening criteria for heat stress exposure. PMID- 17281055 TI - Wireless telecardiological monitoring system for the homecare area. AB - In following the directive "ambulant medical treatment is preferable to in hospital treatment" the home care area is becoming more and more important in western societies. In this paper a system for monitoring cardiological risk patients is presented. Special attention was paid to an automatic detection of life-threatening events and the initiation of immediate help. PMID- 17281056 TI - The Preliminary Study of Unobtrusive respiratory monitoring for e-health. AB - AIn this study, we developed a wearable physiological measurement device (bioshirt). The developed bioshirt can record ECG (lead I, lead II, V1), blood oxygen saturation, 2-axis acceleration, and skin temperature in mobile environment. Sensors are embedded into the bioshirt. It showed noticeable performance in terms of usability and monitoring. Respiration signal is acquired by inductive plethysmograph (IP). However, acquired IP signal is by the upper body movement like arm or abdomen movement. To get correct respiratory signal, we use both IP and EDR (ECG-derived respiration). EDR is used to supplement the IP that is contaminated by some artifact. As result, it provide suitable respiration rate (RR) although IP is contaminated by some noise. PMID- 17281057 TI - Energy-efficient MAC Protocol for Patient Personal Area Networks. AB - The formulation of a Personal Area Network (PAN), consisting of a wireless infrastructure of medical sensors, attached to patient's body, and a supervising device carried by them, lays the path for continuous and real-time monitoring of vital signs without discomforting the person in question. This infrastructure enhances the context of remote healthcare services by supporting flexible acquisition of crucial vital signs, while at the same time it provides more convenience to the patient. Aiming at the exploitation of the inherent features and requirements of wireless medical sensor networks, in this paper we focus on the main design guidelines of a low power Medium Access Control (MAC) protocol, designated to support a patient PAN. The proposed protocol intends to improve energy efficiency in such applications and thus is oriented towards the prevention of main energy wastage sources, such as collision, idle listening and power outspending. PMID- 17281058 TI - Intensive monitoring system design for cardiological rehabilitation. AB - In the present study, we investigate mechanisms which to effectively control patients for cardiac rehabilitation. Cardiac rehabilitation exercise includes many things of our present needs and should observe the conditions of the patients accurately at a different level to be sent to physical therapist (PT). The estimated value should be re-sent to patients as a prescription for cardiac rehabilitation exercise. Also, we ask for mechanism that can handle the emergencies rapidly. The thesis will research upon monitoring system on patients for cardiac rehabilitation, health machine control protocols, heart rate control and alarming system. It can be applied to the systems of cardiac rehabilitation. PMID- 17281059 TI - A Wireless PDA-based Electrocardiogram Transmission System for Telemedicine. AB - A wireless electrocardiogram (ECG) transmission system is developed which integrates current personal digital assistant (PDA) technology and general packet radio service (GPRS) technology. This PDA-based system is comprised of a designed ECG signal acquisition module, a Pocket PC (Legend 5100) and a GPRS communication module. The specific objective of this system is to facilitate accurate and reliable monitoring and transmission of patient's ECG signal. This system is able to acquire ECG signals, display the ECG waveform on the LCD screen of the PDA and wirelessly transmit them to an authorized remote medical ECG management server. The transmission function of this system is tested and the results show that this system is able to accurate and reliable transmit the ECG signal. PMID- 17281060 TI - A WBAN System for Ambulatory Monitoring of Physical Activity and Health Status: Applications and Challenges. AB - Recent technological advances in sensors, low-power integrated circuits, and wireless communications have enabled the design of low-cost, miniature, lightweight, intelligent physiological sensor platforms that can be seamlessly integrated into a body area network for health monitoring. Wireless body area networks (WBANs) promise unobtrusive ambulatory health monitoring for extended periods of time and near real-time updates of patients' medical records through the Internet. A number of innovative systems for health monitoring have recently been proposed. However, they typically rely on custom communication protocols and hardware designs, lacking generality and flexibility. The lack of standard platforms, system software support, and standards makes these systems expensive. Bulky sensors, high price, and frequent battery changes are all likely to limit user compliance. To address some of these challenges, we prototyped a WBAN utilizing a common off-the-shelf wireless sensor platform with a ZigBee-compliant radio interface and an ultra low-power microcontroller. The standard platform interfaces to custom sensor boards that are equipped with accelerometers for motion monitoring and a bioamplifier for electrocardiogram or electromyogram monitoring. Software modules for on-board processing, communication, and network synchronization have been developed using the TinyOS operating system. Although the initial WBAN prototype targets ambulatory monitoring of user activity, the developed sensors can easily be adapted to monitor other physiological parameters. In this paper, we discuss initial results, implementation challenges, and the need for standardization in this dynamic and promising research field. PMID- 17281061 TI - Preliminary results on the study of smart wearable antennas. AB - We report a study on the design, simulation and evaluation of wearable antennas. This work open the way to continuous and automatic monitoring with wearable devices. PMID- 17281062 TI - A Novel Mobile ECG Telemonitoring System. AB - This paper introduces a novel mobile ECG telemonitoring system. By means of CDMA1x (GPSOne) mobile telecommunication network, the system can perform "full time and space" monitoring of human ECG signal, and once the signal of the monitored subject departed from its normal ranges, the hospital ECG monitoring center can further localize his/her geographical position and give rescue in the first time. Another feature of the system is its high anti-interference capability. In order to reduce 50Hz and RF interferences during mobile monitoring, which are usual much serious than conventional hospital monitoring, a new active recording technology was proposed and an active ECG recording electrode was designed. The system has passed the clinical test and used in China. PMID- 17281063 TI - A new method of radio frequency links by coplanar coils for implantable medical devices. AB - A new method based on coplanar coils for the design of radio frequency links has been developed, to realize the communication between the programming wand and the implantable medical devices with shielding container simply and reliably. With the analysis of electronic and magnetic field theory, the communication model has been established and simulated, and the circuit has been designed and tested. The experimental results are consistent with the simulation fairly well. The voltage transfer ratio of the typical circuit with present parameters can reach as high as 0.02, which can fulfill the requirements of communication. PMID- 17281064 TI - eWellness: Building a Smart Hospital by Leveraging RFID Networks. AB - The application of Radio Frequency Identification (RFID) sensor networks pervasively to the hospital environment has the potential to improve efficiencies in operational aspects through accurate capture of fine grained data. The sensor nodes generate large amounts of real or near real-time data. Understanding and managing these data in the context of the hospital pose challenges for the middleware which has to connect sensor networks with hospital applications. In this paper we propose an edgeware paradigm of organizing hospital RFID sensor data based on the notion of an event. The event is defined and its properties are discussed. A three layered event representation and reasoning model is developed to map raw sensory information to semantic events in the application domains. A prototype system, called eWellness is build for the test of the local hospital. PMID- 17281065 TI - Estimation of activity energy expenditure: accelerometer approach. AB - A novel algorithm estimating the calorie expenditure during physical activities is introduced. The physical activity is quantified by the integration of the accelerometer signals obtained from the 3D accelerometer fixed at the waist level of the human body. Simultaneous measurements of activity and calorie expenditure using 3D accelerometer and gas analyzer show the activity calorie expenditure increases as the activity increases with different rates depending on the type of activities (e.g., walking, running) as well as the physical characteristics of the subjects (e.g., gender, age, mass, and height). Based on the experimental data gathered from 94 subjects, we suggest a new algorithm estimating the activity calorie expenditure dependent on the demographic data of the subjects and the types of the activity. PMID- 17281066 TI - An Wearable Energy Expenditure Analysis System based on the 15-channel Whole-body Segment Acceleration Measurement. AB - The measurement of the amount of energy utilized during physical activity has generated considerable interests from various groups ranging from exercise physiologists to nutritionists and fitness center workers. To date, however, the existing energy expenditure estimation methods are not so reliable and compact. In this paper, we propose a new method for accurately and easily estimating energy expenditure during physical activity with a novel algorithm. This method involves acquiring acceleration signals through a 15-channel whole-body segment acceleration measurement system and then estimating the calories expended using a newly developed algorithm. The results of 3 subjects' experiments were compared with a commercially available mask type indirect calorimeter and a 9-axis accelerometry-based calorimeter. The results demonstrate that the proposed method provides a new and reliable way to estimate human energy expenditure during physical activity. PMID- 17281067 TI - Interoperability and security in wireless body area network infrastructures. AB - Wireless body area networks (WBANs) and their supporting information infrastructures offer unprecedented opportunities to monitor state of health without constraining the activities of a wearer. These mobile point-of-care systems are now realizable due to the convergence of technologies such as low power wireless communication standards, plug-and-play device buses, off-the-shelf development kits for low-power microcontrollers, handheld computers, electronic medical records, and the Internet. To increase acceptance of personal monitoring technology while lowering equipment cost, advances must be made in interoperability (at both the system and device levels) and security. This paper presents an overview of WBAN infrastructure work in these areas currently underway in the Medical Component Design Laboratory at Kansas State University (KSU) and at the University of Alabama in Huntsville (UAH). KSU efforts include the development of wearable health status monitoring systems that utilize ISO/IEEE 11073, Bluetooth, Health Level 7, and OpenEMed. WBAN efforts at UAH include the development of wearable activity and health monitors that incorporate ZigBee-compliant wireless sensor platforms with hardware-level encryption and the TinyOS development environment. WBAN infrastructures are complex, requiring many functional support elements. To realize these infrastructures through collaborative efforts, organizations such as KSU and UAH must define and utilize standard interfaces, nomenclature, and security approaches. PMID- 17281068 TI - The study on separability criteria suitable for cardiac data. AB - There is a need to develop a criterion to measure the class separability of cardiac data before the decision-making logic is applied. This article explores the use of separability criteria to measure the separability of cardiac data. Then a new separability criterion was presented, which was constructed by combining standard deviation with Euclidean center distance. The criterion was applied to extract features of cardiac arrhythmias, measure the performance of the features, and build the decision tree for multiclass classification. The data in this study were obtained from MIT-BIH database. The experimental results show that it is an effective and practical separability measurement criterion. PMID- 17281069 TI - ECG Feature Elements Identification For Cardiologist Expert Diagnosis. AB - This paper proposes a reliable method for Cardiologist Expert Diagnosis based on ECG Elements Identification. This method analyzes ECG Key features (P wave, QRS complex, T wave). It includes noise purification, sample design for digital ECG, Understanding of The HP ECG Criteria Program, and The Extended Measurements Report. This project report synthesizes the advantages of Math, Multiple Function Analysis, Database and Knowledge Base, and Expert System to explore the mechanism of "ECG Feature Elements Identification For Cardiologist Expert Diagnosis". This report proposes an integral method of ECG information flow for its area computing and a differential method of ECG information flow for its slope computing and a convolution method for true ECG wave form element extraction even they confuse with each other or incomplete. This method can implement ECG report in real time and provide exact explanations for the diagnostic decision obtained. This method can offer mean (standard) values estimation for parameters and Confident Interval computing for predictive accuracy (above 85%). This method solved following problems: noise purification, incomplete and confusing ECG element's key features identification, Decision-Rule Base, and Expert Diagnosis Model --- For "Cardiologist Expert Diagnosis" research topic. PMID- 17281070 TI - The development of core-type Transcutaneous Energy Transmission System for artificial heart. AB - Recently, Artificial Heart (AH) is recognized as the alternate method of the heart graft. Though there are many problems and defect on AH, long term durability, miniaturization and weight saving interfaced with flow rate performance, efficiency of device. Considering rehabilitation into the society and advancement of QOL (Quality of Life), the construction of power source which supplies electric power to the device is important and has many problems. Especially, the electric feeder line restricts behavior of the transplant recipient and disturbs rehabilitation into the society. For solving these problems, Transcutaneous Energy Transmission System (TETS) is noticed and studied. This study proposes core-type TETS. It achieves high magnetic coupling compared with air-core-type TETS which is carried out on clinical study. Because core-type TETS has high magnetic coupling, it is possible to reduce the input current and to miniaturize transformer size. This paper mentions the characteristic of core-type TETS. PMID- 17281071 TI - Ventricular tachyarrhythmia prediction. AB - Using R-R interval history from 24-hour Holter recorders along with R-R interval history from implantable cardioverter defibrillators (ICD), a particular monotonic heart rhythm acceleration pattern during sinus rhythm, when used as a predictor of an imminent episode of ventricular tachyarrhythmia, can achieve a sensitivity of 44% with corresponding specificity of 94%. A more meaningful quantity than the specificity is the daily rate of Type II error, which is 1.8 event/day in this case. The Type II error rate can be reduced to 0.7 event/day with a nonoptimized sensitivity of 47% by using a double acceleration predictor. PMID- 17281072 TI - Algorithm for Clustering Analysis of ECG Data. AB - To satisfy the difficult requirements of ECG analysis such as large data volume, high accuracy and real-time, a classification algorithm for arrhythmia based on clustering analysis is developed. According to things-of-one-kind-come-together principle, this algorithm uses the similarity of heart cases of the same category and, at the same time, incorporates the factor of individual differences. It analyzes arrhythmia by clustering QRS complex waveforms and applies rhythm analysis as the subordinate method. Verified by eight records of MIT-BIH arrhythmia standard heart electricity database, the clustering correct rate reaches above 90%, which shows that this algorithm can analyze arrhythmia effectively. PMID- 17281073 TI - The simultaneous multiple sites epicardial mapping of ventricular fibrillation. AB - Some recently researches have showed that cardiac electrical activities are chaotic during ventricular fibrillation (VF) [1]. It is very difficult to realize the originations and evolvements of these complex activities by used of non simultaneous mapping techniques. Simultaneous multiple sites epicardial mapping is one of the precise mapping techniques developed in recent years. Fudan University has designed a novel 64/176-channel epicardial mapping system [2]. The new design includes a multi-electrodes patch, 64-channel ECG (electrocardiogram) signal amplifier, 80-channel A/D converter and a PC (personal computer). It uses finite hardware resources to detect depolarization wave from any way, any direction wherever in the whole mapping area. In this article we will discuss the characteristics of the mapping system and some interesting results we have obtained from the animal trials by use of this system. PMID- 17281074 TI - Cardiac State Diagnosis using Adaptive Neuro-Fuzzy Technique. AB - Heart rate signals may either contain indicators of a current disease or even warnings about impending diseases. However, to manually study and pinpoint heart abnormalities in voluminous data is strenuous and time consuming. Here, an adaptive neuro-fuzzy network is used to classify heart abnormalities in ten different cardiac states and shown to be effective. PMID- 17281075 TI - Cardiac Health Diagnosis using Wavelet Transformation and Phase Space Plots. AB - Analysis of heart rate variation (HRV) has become a popular noninvasive tool for assessing the activities of the autonomic nervous system (ANS). HRV analysis is based on the concept that fast fluctuations may specifically reflect changes of sympathetic and vagal activity. It shows that the structure generating the signal is not simply linear, but also involves nonlinear contributions. These signals are essentially non-stationary; may contain indicators of current disease, or even warnings about impending diseases. The indicators may be present at all times or may occur at random in the time scale. However, to study and pinpoint abnormalities in voluminous data collected over several hours is strenuous and time consuming. This paper presents the continuous time wavelet analysis of heart rate variability signal for disease identification. Phase space plots of heart rate signal for a chosen embedding dimension are compared with the wavelet analysis patterns. PMID- 17281076 TI - Support vector machine based error filtering for holter electrocardiogram analysis. AB - Holter electrocardiogram data is analyzed by a computer, however, there is a detection of non-heartbeat as a heartbeat. This study dealt with reduction of the incorrect detection using support vector machine (SVM). By exploiting the power of SVM and human like information processing, the data was classified to heartbeat class or non-heartbeat class. The performance of the proposed method was verified in several experiments and comparing with SVM and neural network, and 96% of accuracy was achieved. PMID- 17281077 TI - A Wavelet Approach to Detecting Electrocautery Noise in the ECG. AB - A software approach has been developed for detecting electrocautery noise in the electrocardiogram (ECG) using a wavelet decomposition of the signal. With this approach, a clinical monitoring expert system can be forewarned of potential artefacts in trend values derived from the ECG, allowing it to proceed with caution when making decisions based on these trends. In 15 operations spanning 38.5 hours of ECG data, we achieved a false positive rate of 0.71% and a false negative rate of 0.33%. While existing hardware approaches detect the source of the noise without any ability to assess its impact on the measured ECG, our software approach detects only the presence of noise in the signal itself. Furthermore, the software approach is cheaper and easier to implement in a clinical environment than existing hardware approaches. PMID- 17281078 TI - Adaptive ventricular rate smoothing during atrial fibrillation: a pilot comparison study. AB - An adaptive ventricular rate smoothing (VRS) algorithm is developed to regularize the ventricular rate during atrial fibrillation (AF) by means of ventricular pacing (VP). Using a quantitative AF-VP model, we conduct pilot study to compare its performance with three other VRS algorithms. Simulations show that all VRS algorithms are effective to stabilize the heart rate during AF when intrinsic ventricular rate is not higher than the maximum pacing rate. The effect of VRS is diminished as the intrinsic ventricular rate increases, whereas slower intrinsic ventricular rate renders more aggressive VP. Compared to other methods, the Adaptive-VRS algorithm tends to stabilize the ventricular rate during AF with less VP, while intrinsic ventricular responses with physiological rate and rhythm are preferably preserved. PMID- 17281079 TI - Modeling defibrillation electrode performance. AB - A Boundary Element (BE) model was developed of the electric potential field in the heart arising from electric potentials applied on implanted defibrillator electrodes. The model solved Laplace's equation for potential and was implemented using the BE method with realistic torso structures. An efficient out-of-core solver was developed, allowing any size problem to be solved, subject only to computer speed and time available. A method was also developed that allowed matrices calculated in one problem to be used in other, similar problems, often reducing calculation times by an order of magnitude. Model validation included comparison with myocardial potentials from a finite element model and clinically found voltage and resistance at defibrillation threshold from 29 patients. The model was used in investigations of transvenous electrode configurations, with potential found for reduction in defibrillation voltage and energy. The BE model was successful in modelling the electric field in the torso, in predicting implantable defibrillator performance and in finding application in electrode performance studies. PMID- 17281080 TI - Comparison of numerical methods applied to field stimulated cardiomyocytes. AB - Different algorithmic approaches to the task of numerically simulating stimplified electro-physiological settings encountered in field stimulation experiments of cardiac preparations are compared. Rapid prototyping environments for dynamic system simulation as well as dedicated liberaries for high performance computing are employed to serve the varying needs. PMID- 17281081 TI - Wavelet Transform-Based ECG Baseline Drift Removal for Body Surface Potential Mapping. AB - This paper gives a new approach for the removal of slow baseline drift components of electrocardiographic (ECG) signals based on the discrete wavelet transform. The baseline drift is efficiently removed by zeroing the scaling coefficients of the discrete wavelet transform. Such approach can easily be combined with other wavelet based approaches for random noise reduction or power line interference reduction. The new pre-processing approach can remove the low-frequency components without introducing distortions in the ECG waveform. PMID- 17281082 TI - Detection of Multilead ECG Character Points and Assessment Based on a Reference Database. AB - A method of multilead ECG character points detection is introduced in this study. The method includes two main sections: the detection of single lead character points and determination of global character points. The method of single lead character points detection is similar to the traditional ones that use the first differential signal of ECG. While some special modification is adopted. The multilead ECG character points are gotten according the single lead result. To make the detection more reliable, an approach of lead optimization is used. In the process of global character points determination, such as the detection of the onset and the offset of QRS, P wave and T wave, the similar methods are used. Since some approaches can be found in several other papers, these processes are not explained into detail. The method is assessed with the CSE database. Since only part reference of CSE database is published, the test result is base on the MA1 data set which reference points are published. The result reveals that the method of detecting the fiducial point of P and QRS has similar accuracy as referee or average result of other computer program. While method of detecting the offset of T may need further improvement. In addition, to test the method stability and reliability, the character points of the CSE's other data set (MA2, MO1, MO2) are also marked beat by beat manually. Then another assessment based on ourselves reference is also executed. The result is similar to the MA1 test result. PMID- 17281083 TI - QT Interval Measurement based on Singular Value Decomposition. AB - This paper describes a method for accurate and stable measurement of ECG QT intervals. ECG signals from multiple leads are decomposed into orthogonal signals by the algebraic method of singular value decomposition. Major orthogonal signal components are then selected and root total power signal is formed. The root total power signal is found to be stable in its waveform and suitable for Q and T end time determination by the aid of either least square or tangential line fit. Illustrative examples are chosen from normal, long QT syndrome (LQTS) and left ventricular hypertrophy (LVH) subjects to demonstrate the effectiveness of the proposed method. Automatically measured QT intervals are also compared to those estimated by eye fit of an experienced cardiologist. PMID- 17281084 TI - ECG Feature Extraction Based on Multiresolution Wavelet Transform. AB - In this work, we have developed and evaluated an electrocardiogram (ECG) feature extraction system based on the multi-resolution wavelet transform. ECG signals from Modified Lead II (MLII) are chosen for processing. The result of applying two wavelet filters (D4 and D6) of different length on the signal is compared. The wavelet filter with scaling function more closely to the shape of the ECG signal achieved better detection. In the first step, the ECG signal was de-noised by removing the corresponding wavelet coefficients at higher scales. Then, QRS complexes are detected and each complex is used to locate the peaks of the individual waves, including onsets and offsets of the P and T waves which are present in one cardiac cycle. We evaluated the algorithm on MIT-BIH Database, the manually annotated database, for validation purposes. The proposed QRS detector achieved sensitivity of 75. 2 % 18 . 99 .. and a positive predictivity of 45 . 4 % 00 . 98 .. over the validation database. PMID- 17281085 TI - Quick QRS Complex Detection for On-Line ECG and Holter Systems. AB - This paper presents a new QRS complex detection algorithm that can be applied in various on-line ECG processing systems. The algorithm is performed in two steps: first a wavelet transform filtering is applied to the signal, then QRS complex localization is performed using a maximum detection and peak classification algorithm. The algorithm has been tested in two phases. First the QRS detection in ECG registrations from the MIT-BIH database has been performed, which led to an average detection ratio of 99.5%. Then, the algorithm has been implemented into a microcontroller-driven portable Holter device. PMID- 17281086 TI - Development of detection algorithm of fatal arrhythmia for a new implantable cardioverter defibrillator. AB - This study discusses the validity of new methods of detecting fatal arrhythmia used for ICDs. The method utilizes the steady state gain of the system from the ECG signal to the ventricular volume signal. After analyzing the data measured in a dog, it has been shown that the system can be approximated by a second order resonant system. Moreover, it has been indicated that the batch-type least squares method with the short data window shifting every time the R-wave occurs is better rather than a few versions of recursive algorithms for identifying time varying parameters. PMID- 17281087 TI - Development of Eddy Current Sensor systems in artificial heart for noncontact gap sensing. AB - The axial flow pump has been developed in Korea Artificial Organ Center. It consists of an impeller, a motor and a magnetic bearing. The magnetic bearing fully levitates the impeller not to contact with other parts of pump. However, in order to control the gap between the impeller and other parts, continuous gap sensing is necessary. The conventional gap sensors are relatively large to implant in artificial heart. Thus, the compact eddy current sensor system proper for artificial heart was developed and the performances were evaluated. It showed good results and has small size. However, the dependency of the sensor upon temperature and target material was shown also. Moreover, the output of sensor had nonlinear responses. These must be calibrated in further study. PMID- 17281089 TI - Quadratic Model Predicts Lesion Outcome for the CARDIMA Cardiac Electrophysiology Radiofrequency Ablation System. AB - This study investigates the CARDIMAreg electrophysiology (EP) radiofrequency (RF) ablation system characteristics to create linear lesions in a blood flow environment on cardiac tissue. We developed an in-vitro experimental platform that simulates a cardiac electrophysiology ablation procedure within the pumping atria on myocardium tissue. The INTELLITEMPreg energy management device was used to control RF energy delivery to the REVELATIONreg T-Flex, an eight electrode, eight thermocouple deflectable electrophysiology linear ablation catheter to form the linear lesions. An experimental design employing a response surface central composite model was used; the range of ablation parameters for target temperature and ablation duration were chosen based on achieving optimum rotatability and orthogonality for the experimental design model where the parameters for each factor were spaced at or close to the limits of the INTELLITEMP EP's equipment settings. The results show that this system is capable of forming clinically relevant deep and contiguous endocardial cardiac lesions in a blood flow environment, with minimal or no electrode residue. PMID- 17281090 TI - REALITY in Home Telecare: A Systemic Approach to Evaluation. AB - This paper describes the REALITY telecare system, designed to enable a range of commonly occurring chronic diseases to be managed in the home setting. This uses hand-held computers linked to the internet for collecting and transmitting clinical and quality of life data and providing remote clinical advice. Key to the success of such telecare is a proper scheme of evaluation. An overall framework for such evaluation is proposed. Within this schema formative evaluation results are presented, focusing particularly on technical issues being addressed, patient recruitment and retention, and data collection. User acceptability is then considered as a first ingredient of summative evaluation. PMID- 17281088 TI - Use of 3D Potential Field and an Enhanced Breadth-first Search Algorithms for the Path Planning of Microdevices Propelled in the Cardiovascular System. AB - Potential field algorithms often used in path finding applications on a 2D plane are expanded onto a 3D map trajectories for navigation planning of a microdevice designed to be propelled through the cardiovascular system using magnetic gradients generated by a clinical MRI system. This system assembles a 3D reconstruction of a cardiovascular system through magnetic resonance angiography images. The method also allows the extraction of the physiological properties of the given network. PMID- 17281091 TI - Information Technology for Assisted Living at Home: building a wireless infrastructure for assisted living. AB - A heterogeneous wireless network to support a Home Health System is presented. This system integrates a set of smart sensors which are designed to provide health and security to the elder citizen living at home. The system facilitates privacy by performing local computation, it supports heterogeneous devices and it provide a platform and initial architecture for exploring the use of sensors with elderly people in the Information Technology for Assisted Living and Home project. The goal of this project is to provide alerts to care givers in the event of an accident or acute illness, and enable remote monitoring by authorized and authenticated care givers. PMID- 17281092 TI - A mobile teleconference system for homecare services. AB - Telemedicine with mobile communications is a new research area aimed at providing highly flexible medical services that are not possible with standard telephony. In this article, a teleconference system via mobile Internet connections for homecare service is presented. An important purpose of this system is the realization of real time communication between the service station (experts) and the service providers (nurses) in mobile conditions. The following functions are realized via mobile internet connections: 1) a communication control platform for data transmission and process management; 2) whiteboard function to share image and draw free lines; 3) voice transmission between service station and service providers; 4) system management including data maintenance and database access. In this system, still images and voice data are transmitted in real time between service providers (patient's home site) and service managers (station site). This study is a new trial to support homecare service with mobile telecommunication technology. PMID- 17281093 TI - Fully automatic system for monitoring blood pressure from a toilet-seat using the volume-oscillometric method. AB - Daily monitoring of health condition at home is very important subject not only as an effective scheme for early diagnosis and treatment of cardiovascular and other diseases, but also for prevention and control of such diseases. From this point of view, we have been developing a fully automated "non-conscious" monitoring system for home health care. In this paper are described, structural detail of a newly developed toilet-seat-installed blood pressure measurement system and some results obtained by the system. Also described is outline of a newly designed system for measuring hydrostatic pressure difference between the heart and the measuring site, i.e., thigh, during blood pressure measurement. PMID- 17281094 TI - Building a High-Quality Mobile Telemedicine System using Network Striping over Dissimilar Wireless Wide Area Networks. AB - This paper describes an approach to building a high-quality mobile telemedicine system that overcomes the limitations of individual public wireless data networks. Public wireless data channels do not have the capacity to handle the high-bandwidth video needed for applications such as remote evaluation of trauma and stroke patients. Network striping allows us to aggregate multiple physical channels to meet the bandwidth requirements for the video. We have developed flexible network-striping software middleware, and are building a telemedicine system using that middleware. Our approach uses existing communications infrastructure and conventional-off-the-shelf components, making the system easy to deploy. PMID- 17281095 TI - Long-term Phonocardiographic Fetal Home Monitoring for Telemedicine Systems. AB - A novel compact method for fetal home monitoring optimized for long data acquisition time and low communication costs is presented. The method incorporates the preprocessing of disturbed acoustic signal received on the maternal abdomen. The basic idea of the preprocessing is that the detection of the systolic and diastolic sounds takes place on two separated frequency bands with autocorrelation on predicted time intervals. Measurements on 47 selected pregnant women have shown that the use of this method significantly reduces the amount of data to be transferred to the computer centre in the hospital, where only the very disturbed time periods have to be evaluated. Based on this method a new, phonocardiographic fetal telemedicine system can be built without time limitation of measurements. PMID- 17281096 TI - Performance analysis of a home telemonitoring system. AB - Performance analysis is important for evaluating the system effectivity. In this paper, the queueing theory and discrete event simulation technology are applied to a performance study of a home ECG telemonitoring system. The data from a four month trial is used to establish the input stream model of the medical service system. The input model includes the customer inter-arrival time distribution and the service time distribution of the server. With the input model, a queueing model is introduced to simulate the ECG monitoring system. The performance simulation results indicate the feasibility of the model. The results are helpful on designing an optimal service system with given properties of input stream and service procedures. PMID- 17281097 TI - Transfer function analysis of carotid sinus baroreceptor transduction. AB - The carotid sinus baroreflex is one of the most important negative feedback systems that regulate arterial pressure. The neural arc transfer function from carotid sinus pressure (CSP) input to efferent sympathetic nerve activity shows a gain increase of approximately 10 dB when input frequency increases from 0.01 to 0.5 Hz. The transfer gain of the neural arc decreases in the frequency range above 0.8 Hz. The aim of the present study was to elucidate the extent of contribution of the carotid sinus baroreceptor transduction to the determination of the neural arc dynamic characteristics. In 7 anesthetized rabbits, we isolated the right carotid sinus and controlled CSP while recording afferent nerve activity (ANA) from the carotid sinus nerve. CSP was randomly assigned to either 80 or 120 mmHg with a switching interval of 50 ms according to a binary white noise signal for 15 min. The transfer function from CSP to ANA was estimated in the frequency range from 0.01 to 3 Hz. The transfer function showed a gain increase of approximately 4.6 dB when input frequency increased from 0.01 to 0.3 Hz. The transfer gain remained relatively constant up to 3 Hz. These results suggest that the carotid sinus baroreceptor transduction partly contributes to the gain increase of the baroreflex neural arc in the frequency range from 0.01 to 0.5 Hz but not the gain decrease above 0.8 Hz. PMID- 17281098 TI - Identification of the arterial and cardiopulmonary total peripheral resistance baroreflex gain values from spontaneous hemodynamic variability. AB - We have previously proposed a potentially noninvasive technique for determining the closed-loop gain values of the arterial and cardiopulmonary total peripheral resistance (TPR) baroreflex systems by mathematical analysis of beat-tobeat fluctuations in arterial blood pressure, cardiac output, and stroke volume. In this paper, we describe an evaluation of the technique with respect to spontaneous hemodynamic variability measured from seven conscious dogs before and after chronic arterial baroreceptor denervation. We report that the technique correctly predicted the expected changes in the TPR baroreflex gain values induced by the baroreceptor denervation. PMID- 17281099 TI - Chronic vagal stimulation decreased vasopressin secretion and sodium ingestion in heart failure rats after myocardial infarction. AB - Chronic vagal stimulation (VS) markedly improved long-term survival in the heart failure rats. We examined the effects of VS on arginine vasopressin (AVP) secretion and salt ingestion in heart failure rats after myocardial infarction (MI). Surviving rats after MI were randomly assigned to two groups. One group was treated with sham stimulation (SS), and the other group was treated with VS. All rats could access water and 1.8% NaCl solution ad libitum. Treatment started at 2 weeks after MI, and continued for 6 weeks. We monitored drinking behavior during treatment. At the end of treatment, we measured hemodynamics and plasma levels of AVP and brain natriuretic peptide (BNP). The plasma AVP and BNP levels were significantly lower in the VS group than the SS group. VS significantly inhibited the ingestion of 1.8% NaCl solution. The normalized biventricular weight of the VS group was significantly lower than that of the SS group. The VS group had significantly lower left ventricular end-diastolic pressure, and higher cardiac index than the SS group. In conclusion, these results suggest that chronic VS regulates the water balance by suppression of plasma AVP level and salt ingestion in the heart failure rats after MI. PMID- 17281100 TI - Residual pulse morphology visualization and analysis in pressure signals. AB - We describe a new method to determine whether there is additional information contained in the intracranial pulse morphology that cannot be explained by covariation with the mean intracranial pressure (ICP) alone. Our procedure calculates and displays the difference between the actual pulse morphology and the expected morphology given a predictor variable, such as the mean ICP. The display is intuitive and permits easy recognition of changes in morphology unaccounted for by the given predictor variable. This method can be applied to any signal that consists of a series of events that generate a consistent morphology that is correlated to other predictor variables. Our exploratory analysis of ICP signals revealed examples of changes in pulse morphology that were independent of mean ICP. This suggests the need for further work that examines the underlying physiology responsible for pulse morphology. PMID- 17281101 TI - Calibration of the photoplethysmogram to arterial blood pressure: capabilities and limitations for continuous pressure monitoring. AB - It is well known that the photoplethysmogram (PPG) is related to the underlying arterial blood pressure (ABP). However, there is ambiguity regarding the precise relationship of these two circulatory signals: some investigators have described a static relationship, while others have used more complex dynamic characterizations. This paper attempts to reconcile these models, employing results obtained from controlled human subject tests. Our data indicate that there is no simple relationship between the continuous PPG and ABP. However, when several serial beats are aggregated, a static, reproducible relationship is observed. This suggests that, in a stable experimental environment, most of the factors that decouple the ABP and PPG operate over short time scales. When these factors are eliminated through beat averaging, calibrated plethysmography offers a near-continuous estimation of ABP. Our data suggest that this PPG/ABP relationship is not stationary, since it is less consistent over time scales greater than 20 minutes. Variable local ABP was generated by raising and lowering the subjects' hands; this method also offered the means for oscillometric BP measurement without any additional actuator such as a conventional pneumatic cuff. PMID- 17281102 TI - The estimation of cerebral metabolic rate of O2 from Near Infra-Red Spectroscopy. AB - The accurate estimation of cerebral metabolic rate of O2 (CMRO2) is still an unavailable but highly desired clinical tool. The addition of a further experimental variable to Near Infra-Red Spectroscopy (NIRS) allows more information to be gained than has previously been possible. A physiological model is presented here that can be used to estimate CMRO2 from measurements of oxy- and deoxy- haemoglobin and oxygen saturation. It is shown that under steady state conditions, CMRO2 can be estimated accurately, despite the system of equations being underdetermined, partly since the parameters that have to be provided are physiologically meaningful and thus unlikely to vary over a wide range. Initial simulations under dynamic conditions seem to support the hypothesis that dynamic changes in CMRO2 can also be estimated accurately, although this is still work in progress. PMID- 17281103 TI - Application of information theory to the assessment of data integrity for coded aperture imaging. AB - The SPECT imaging process has two fundamental stages: detection and display. The detection stage can be rigorously quantitatively described by Shannon's information theory. Information is transferred from the source to the detector in the photon emitting process. In the detection stage, integrity of projection data can be assessed by the information entropy, which is the conditional entropy standing for the average uncertainty of the source object under the condition of projection data. Simulations were performed to study projection data of emission computed tomography with a coded aperture collimator. Several types of coded aperture collimators were treated. Results demonstrate that the conditional entropy shows the data integrity, and indicate how the algorithms are matched or mismatched to the geometry. A new method for assessing data integrity is devised for those decision makers. PMID- 17281104 TI - Computer assisted analysis of microtubule dynamics in living cells. AB - Microtubules are dynamic polymers that rapidly transition between states of growth, shortening, and pause. These dynamic events are critical for basic cellular processes, especially cell division. Typically, these events are quantified by imaging microtubule movements over time, which results in large data sets that require rigorous quantitative analysis. In most cases, these analyses are performed manually by the researcher. This process is both tedious and prone to error; thus an efficient and reliable computer-assisted quantification system would provide a rapid approach, suitable for high throughput data analysis. In this paper, we describe methods to automatically segment and track microtubule movements. Our method is a snake based method [1]. Instead of a closed contour, we use an open contour to track individual microtubule. We redefine some of the internal energy terms specifically for open snake. A new external energy term for locating the end points of a microtubule is also defined. Testing is done using simulated images and untreated MCF-7 breast cancer cell lines as well as cells treated with the microtubule-targeting chemotherapeutic agent, Taxol. PMID- 17281105 TI - Topographic modeling of cellular images. AB - Modeling the three-dimensional (3D) microscopic cellular images analytically is rather a difficult task due to their random shapes and deformable characteristics. One remedy is to use the topographic structures to approximate the sample surfaces and produce the unknown molecular structures by means of deformable shape generation methods from the topographic models. Here, a training sample set of 3D images is collected for shape discrimination. Morphological watersheds are applied to isolate the cells from the surrounding background. Each detected particle is enclosed within a bounding-box for contrast independent analysis. Topographical structures are adopted to model particle classes and the classification is performed in minimum Euclidian-distance sense. Our experiments show that cell images can be identified consistently in topographic structure means. PMID- 17281106 TI - Visualizing the Regenerated Peripheral Nerve In vivo and In vitro. AB - The morphological changes of regenerated peripheral nerve fibers after injury are closely related with its function recovery. Knowledge of the characteristics of regenerated peripheral nerve on histological level, even that on the molecular level is important for the studies of peripheral nerve regeneration. Here, we present some new methods not only for visualizing the three-dimensional (3D) microstructure and ultrastructure of regenerated nerve fibers in vivo, but also for visualizing the subcellular spatial distribution of mRNA of nerve growth factor (NGF) in living Schwann cells in vitro. The proposed methods should prove to be a valuable tool for investigating the morphological characteristics of regenerated peripheral nerve fibers, as well as the spatio-temporal patterns of gene activity in peripheral nerve injury and regeneration. PMID- 17281107 TI - Identifying Differences in the P600 Component of ERP-Signals between OCD Patients and Controls Employing a PNN-based Majority Vote Classification Scheme. AB - In the present study an attempt was made to focus in the differences between Obsessive-Compulsive Disorder (OCD) patients and healthy controls, as reflected by the P600 component of event-related potential (ERP) signals, to locate brain areas that may be related to Working Memory (WM) deficits. Neuropsychological research has yielded contradicting results regarding WM in OCD. Eighteen patients with OCD symptomatology and 20 normal controls (age and sex matched) were subjected to a computerized version of the digit span Wechsler test. EEG activity was recorded from 15 scalp electrodes (leads). A dedicated computer software was developed to read the ERP signals and to calculate features related to the ERP P600 component (500-800 ms). Nineteen features were generated, from each ERP signal and each lead, and were employed in the design of the Probabilistic Neural Network (PNN) classifier. Highest single-lead precision (86.8%) was found at the Fp2 and C6 leads. When the output from all single-lead PNN classifiers fed a Majority Vote Engine (MVE), the system classified correctly all subjects, providing a powerful classification scheme. Findings indicated that OCD patients differed from normal controls at the prefrontal and temporo-central brain regions. PMID- 17281108 TI - The preparation and characterization of gas bubble containing liposomes. AB - Liposomes and lipid nano-particles containing gas bubbles have great potentials to be used as ultrasound contrast agents or as drug and gene delivery vehicles. We developed a method to enable in situ CO2gas bubbles formation inside liposomes. The resulted bubbles containing liposomes were shown to be able to effectively echo ultrasound. Their acoustic properties were assessed by ultrasound imaging and intensity analysis. Compared to most other echogenic liposome formulations reported, our method is easier, faster, and more economical. It would be useful for many applications with improvements and optimization. PMID- 17281109 TI - Volume Calculation of Venous Thrombosis Using 2D Ultrasound Images. AB - Venous thrombosis screening exams use 2D ultrasound images, from which medical experts obtain a rough idea of the thrombosis aspect and infer an approximate volume. Such estimation is essential to follow up the thrombosis evolution. This paper proposes a method to calculate venous thrombosis volume from non-parallel 2D ultrasound images, taking advantage of a priori knowledge about the thrombosis shape. An interactive ellipse fitting contour segmentation extracts the 2D thrombosis contours. Then, a Delaunay triangulation is applied to the set of 2D segmented contours positioned in 3D, and the area that each contour defines, to obtain a global thrombosis 3D surface reconstruction, with a dense triangulation inside the contours. Volume is calculated from the obtained surface and contours triangulation, using a maximum unit normal component approach. Preliminary results obtained on 3 plastic phantoms and 3 in vitro venous thromboses, as well as one in vivo case are presented and discussed. An error rate of volume estimation inferior to 4,5% for the plastic phantoms, and 3,5% for the in vitro venous thromboses was obtained. PMID- 17281110 TI - Absolutely lossless compression of medical images. AB - Data in medical images is very large and therefore for storage and/or transmission of these images, compression is essential. A method is proposed which provides high compression ratios for radiographic images with no loss of diagnostic quality. In the approach an image is first compressed at a high compression ratio but with loss, and the error image is then compressed losslessly. The resulting compression is not only strictly lossless, but also expected to yield a high compression ratio, especially if the lossy compression technique is good. A neural network vector quantizer (NNVQ) is used as a lossy compressor, while for lossless compression Huffman coding is used. Quality of images is evaluated by comparing with standard compression techniques available. PMID- 17281111 TI - Use of a JPEG-2000 Wavelet Compression Scheme for Content-Based Ophtalmologic Retinal Images Retrieval. AB - In this paper we propose a content based image retrieval method for diagnosis aid in diabetic retinopathy. We characterize images without extracting significant features, and use histograms obtained from the compressed images in JPEG-2000 wavelet scheme to build signatures. The research is carried out by calculating signature distances between the query and database images. A weighted distance between histograms is used. Retrieval efficiency is given for different standard types of JPEG-2000 wavelets, and for different values of histogram weights. A classified diabetic retinopathy image database is built allowing algorithms tests. On this image database, results are promising: the retrieval efficiency is higher than 70% for some lesion types. PMID- 17281112 TI - Fuzzy clustering of CT images for the measurement of hydrocephalus associated with tuberculous meningitis. AB - Computed tomography is used as an aid in the diagnosis of tuberculous meningitis (TBM) for the examination of a number of visual indicators of the disease. We present an algorithm that uses modified fuzzy c-means clustering to segment CT images of the brain into different tissue types. The ventricle/brain ratio is then calculated to measure hydrocephalus, a common sign of TBM in children. PMID- 17281113 TI - Fuzzy entropy based detection of suspicious masses in digital mammogram images. AB - Mammography is the standard method for screening and detecting breast abnormalities. In this paper, we propose a novel scheme for suspicious lesion detection in digital mammograms. The proposed scheme is based on image thresholding. The optimal threshold is determined by minimizing the fuzzy entropy of the image. Moreover, the paper introduces a new block-based performance criterion to compare between the computer generated and the radiologist segmented images. Experimental results over a set of sample images showed that the proposed scheme produces accurate segmentation results when compared with the manual results produced by radiologists. Hence the proposed scheme can be used as an effective tool in monitoring and detecting suspicious lesions on digital mammogram images. PMID- 17281114 TI - Ultrasonic fragmentation of microbubbles: a theoretical approach of the flash in flash-echo. AB - Predicting the dynamic behavior of ultrasound insonified lipid-shelled microbubbles has been of much clinical interest. For perfusion measurements, a technique named flash-echo has been proposed. A burst of high-MI ultrasound is to destroy the contrast agent bubbles, supposedly resulting in a strong scattering signal that is visible on the B-mode image: the flash. The absence of this strong response in parts of the B-mode image indicates a (too) low perfusion. In this paper, we investigate how microbubbles collapse and fragment. An overview of fragmentation theory is given, followed by some high-speed optical observations of collapsing and fragmenting microbubbles in an ultrasonic field. Fragmentation occurs exclusively during the collapse phase. We hypothesize that fragmentation will only occur if and only if the kinetic energy of the collapsing microbubble is greater than the instantaneous bubble surface energy. In contradiction to the assumption that the Blake critical radius is a good approximation for a fragmentation threshold, our simulations show Rmax/R0<<2 for most microbubbles. PMID- 17281115 TI - Activation of Mitochondrial ATP-Sensitive Potassium Channel Contributes to Protective Effect in Prolonged Myocardial Preservation. AB - To find a better strategy for effective donor organ preservation, here we used a model of long-term hypothermia preservation of rat hearts to investigate the cardioprotective effects of diazoxide, a selective opener of mitochondrial ATP sensitive potassium channel (mitoKATP ). Cardiac function was impaired by 8-hour ischemic preservation following 30 minutes of reperfusion. Treatment with diazoxide significantly attenuated the decline of myocardial contractility, and decreased the lactate dehydrogenase leakage and myocardial edema. Diazoxide also prevented the loss of activity of mitochondrial superoxide dismutases and sarcolemmal Na+/K+ ATPase during ischemia or reperfusion period, respectively. These effects of diazoxide could be abolished by a selective mitoKATp blocker 5-hydroxydecanoate. The results suggest that diazoxide, as a supplementation in cardioplegic solution, could enhance myocardial protection by opening mitoKATp channel, and better maintenance of mitochondrial anti-oxidative enzyme. PMID- 17281116 TI - Optical Potential Mapping of the Excitation Process in the Field stimulated Guinea pig Papillary Muscle using short Pulses. AB - We have performed optical potential mapping in guinea pig papillary muscles during the application of short electrical pulses (1ms). Our results showed, that pulses near threshold, which caused membrane depolarizations in the monitored area, can lead to action potential upstrokes which show pronounced differences in the occurrence times (taken at 50% of action potential amplitude) in the range of 4 ms in an area of 0.5 x 0.5 mm2. The pulse induced membrane voltages within the same area, taken at pulse offset, covered the range from 21 to 42 mV. In general, as expected, increasing membrane voltages caused shorter upstroke delays, but this was not always the case resulting in a weak correlation of a linear fit (r=0.57). These findings indicate that the excitation process is based on both, the membrane properties and the tissue structure. Weak pulses near threshold may be applied to trigger action potentials with low, pulse induced disturbances; however, spatially distributed delays within the area of early depolarizations may have to be considered. PMID- 17281117 TI - A Polynomial Approximation Approach for Analyzing ST Shape Change. AB - ST segment is the most important diagnostic parameter to finding myocardial ischemia. Generally physicians make theirs effort to find the change of ST level and shape in ECG to diagnose myocardial ischemia. Most of algorithms that have been developed until now place importance on the ST segment depression and elevation. However, ST change in shape is also good parameter to find a heart disease and it should be considered prudently. The aim of this study is to detect the change of ST in shape using a polynomial approximation method. The developed algorithm finds the least squares curve for the data between S wave and T wave in ECG and calculates the variance of ST shape. An approximate curve of ST is represented by one polynomial over the whole ST or three polynomials for the segmented ST by three parts. The algorithm considers only the relative change of ST shape based on the reference ST, normal shape typically. From the results of the developed algorithm, we can acquire visually the information about the place to include the change of ST shape in the test ECG provided by European ST database. PMID- 17281118 TI - 3D Heart Simulation And Recognition Of Various Events. AB - This paper presents a new way to solve the inverse problem of electrocardiography in terms of heart model parameters. The developed event estimation and recognition method is based on an optimization system of heart model parameters. An ANN-based preliminary ECG analyzer system has been created to reduce the searching space of the optimization algorithm. The optimal model parameters were determined by minimizing the objective functions, as relations of the observed and model-generated body surface ECGs. The final evaluation results, validated by physicians were about 86% correct. Starting from the fact that input ECGs contained various malfunction cases, such as Wolff-Parkinson-White (WPW) syndrome, atrial and ventricular fibrillation, these results suggest that this approach provides a robust inverse solution, circumventing most of the difficulties of the ECG inverse problem. PMID- 17281119 TI - Sensitivity analysis of cardiac electrophysiological models using polynomial chaos. AB - Mathematical models of biophysical phenomena have proven useful in the reconstruction of experimental data and prediction of biological behavior. By quantifying the sensitivity of a model to certain parameters, one can place an appropriate amount of emphasis in the accuracy with which those parameters are determined. In addition, investigation of stochastic parameters can lead to a greater understanding of the behavior captured by the model. This can lead to possible model reductions, or point out shortcomings to be addressed. We present polynomial chaos as a computationally efficient alternative to Monte Carlo for assessing the impact of stochastically distributed parameters on the model predictions of several cardiac electrophysiological models. PMID- 17281120 TI - Potential of Poly-(N-Isopropylacrylamide) hydrogel as a clamper of the microrobot in gastrointestinal tract. AB - We successfully demonstrate that a thermally actuated reversible hydrogel, the poly N-Isopropylacrylamide (PNIPAAm), based clampers holds the intestines of a pig during the inchworm motion of microrobot. Although there are no direct relationship between hydro affinity and friction force, we found the significant friction force difference according to the surface condition change of PNIPAAm hydrogel. On the small intestine of a pig, a clamping mechanism was realized based on simple switching hydrophobic/hydrophilic surface conditions of PNIPAAm due to heating/cooling. In order to estimate response time of the clamper, the characteristic transition time of PNIPAAm film from hydrophilic to hydrophobic condition was investigated. Water contact angle (WCA) was monitored to normalize the transition time characteristics of PNIPAAm film in the course of time. From these results, we calculated the minimum heating time of the various thickness of PNIPAAm film to the clamping after its change to the hydrophobic condition. The minimum heating time was 15 seconds until 1 mm thickness of PNIPAAm film had enough friction force. PMID- 17281121 TI - Robotics for functional recovery in stroke. AB - Multiple robotic systems are under development for training of both upper and lower extremity function in neurologically impaired subjects with spinal cord injury or stroke, yet we currently lack the framework for designing and evaluating mechanical devices and approaches for treatment of such disorders. This paper will describe possible approaches towards evaluating the optimal approach for rehabilitation treatment of such disorders. PMID- 17281122 TI - The Development of M3S-Based GPS Navchair and Tele-Monitor System. AB - The purpose of this study is to develop a M3S- Based GPS navigation system for power wheelchair. The wheelchair steered with GPS and electronic compass can move automatically toward a specific destination through a GIS-Map in the computer. The topic of this study is to help people with disabilities regain independence of transportation in specific areas of their daily activities. This system is now designed to operate in special locations, for example, campuses or airports. Safety of the system is enhanced according to "M3S", which is an international standard for power wheelchair. In the proposed architecture, modules are easily and securely integrated to the wheelchair, which includes a tele-monitor system implemented with computer network, mobile-phone and physiological sensors. Bio signals, wheelchair location and other information of the user are acquired by the nursing staff or any other medical personnel by using this system. PMID- 17281123 TI - Expandable Non-invasive Prostheses - an Alternative to Pediatric Patients with Bone Sarcoma. AB - In the paper the problem of joint arthroplasty in children who have not reached their maturity is raised. The arthroplasty concerns replacement of a joint that does not function due to bone sarcoma that a child suffers from. Osteosarcoma and Ewing's sarcoma are the most common types of pediatric bone cancer and they afflict mainly long bones, i.e. femur and tibia. In such cases there are only two options: to amputate the affected limb or to replace the diseased bone. It goes without saying that the latter solution is most acceptable by patient and surgeon. However, a special prosthesis has to be applied as the limbs still grow. To avoid leg length discrepancy between the healthy limb and the affected one expandable prostheses are inserted. Specific designs of such prostheses allow one to lengthen the operated limb and preserve the same length of the two legs. In the paper an overview of expandable prostheses is presented. Also our own designs of expandable orthopaedic devices are shown. The devices are characterised by the fact that their length can be intelligently extended by means of a special electro-magnetic set. PMID- 17281124 TI - Stress analysis of osseointegrated transfemoral prosthesis: a finite element model. AB - In this study a three dimensional finite element model was established to analyze the interfacial stress distribution in the osseointegrated transfemoral prosthesis. The effects of implant length and screw pitch on the stress and strain distributions were analyzed in terms of bonded and contact bone-implant interfaces. The influences of the contact parameters, contact stiffness and friction coefficient, of the model were evaluated. The results show the differences on the stress distributions at the bone-implant interface in the models with different implant lengths and thread pitches. The highest stress in the model with contact interface is higher than that in the bonded model. PMID- 17281125 TI - Towards Improved Myoelectric Prosthesis Control: High Density Surface EMG Recording After Targeted Muscle Reinnervation. AB - The control of shoulder disarticulation prostheses remains a challenging problem. Recently, a novel method, using targeted muscle reinnervation to develop additional myoelectric control sites, has improved the control of myoelectric upper limb prosthesis in a patient with bilateral amputations at the shoulder disarticulation level [1]. Encouraged by this achievement, we recorded high density surface electromyogram (EMG) signals from the patient's reinnervated muscles as he actuated a variety of different movements. We believe that the reinnervated muscle activation patterns revealed by the high density EMG recording have the potential to further improve the myoelectric prosthesis control. As the initial stage of the study, this paper presents the experiment of high density surface EMG recording, the preliminary EMG data analysis and the framework for future investigation with advanced feature extraction and pattern recognition techniques. PMID- 17281126 TI - Geometric Framework linking different levels of the Biological Continuum. AB - With the increasing importance of molecular and cellular biology, a new type of medicine, molecular based medicine, is now developing. This will significantly alter the way in which medicine is practiced. Central to these developments is the concept of the Biological Continuum (BC). Medicine today is often practiced at one or two of these levels, i.e. there is generally no vertically integrated approach. In any area of application there will be a wide range of data (both 2-D and 3-D) across the BC. Hence, there is a need to readily access and view the full range of data. In this paper we describe a web-based interface which allows the user to view images and other data, and to navigate seamlessly from one level of the BC to another level (e.g. from Visceral to Tissue). We present a geometric framework to link images from these two levels. The interface was developed using SVG and Javascript. An example case study, which focuses on the knee, is presented MR images of knee at the visceral level and histology images of cartilage at the tissue level. We have shown that with such an interface it is possible to view images from different levels of the BC in a vertically integrated manner. PMID- 17281127 TI - The Study on Virtual Medical Instrument based on LabVIEW. AB - With the increasing performance of computer, the virtual instrument technology has greatly advanced over the years, and then virtual medical instrument technology becomes available. This paper presents the virtual medical instrument, and then as an example, an application of a signal acquisition, processing and analysis system using LabVIEW is also given. PMID- 17281128 TI - Partial function introducing of the management system of ultrasonic digital image in visual c++.net condition. AB - This paper presents the management system of ultrasonic digital image. The system is put forward because PACS technology prevails with various hospitals. The idea that we put forward the system is that we use modem computer and network technology setting up the mini-PACS. PMID- 17281129 TI - Design of an Incubator for Premature Infant Based on LabVIEW. AB - This paper introduces the system structure, hardware circuits, control algorithms, and software program of the incubator for premature infant based on LabVIEW. The main advantages of this device are that preheating is less time than others, the capability of meeting of emergency is provided, control track of temperature and humidity are visible, operation is easy to clinical practice, and maintainability is possessed. PMID- 17281130 TI - Basic Study for Optimal Control of In-Bed Temperature during Sleep. AB - It is important to create a comfortable environment to restful sleep. In this study, we trial-produced an in-bed temperature control system. At first, we statically controlled the temperature in the subject's bed at 32°C by using the system, and examined how this control affected sleep. We were able to confirm that the ratio of slow-wave sleep (SWS) increased in comparison to cases in which the temperature in the bed was not controlled. Next, the temperature in the subject's bed was dynamically controlled at temperature change patterns according to sleep cycles that is as follows; Heating during the REM sleep period and cooling during the SWS sleep period were conducted n the range of 32±2°C, and the case of the opposite phase. The result showed that cooling during the REM period increased the REM sleep share rate. Based on these results, an increase of the REM sleep share rate at around 30°C could be confirmed, indicating a possibility that the REM period thermoneutrality zone shifted to a lower temperature, compared with that of SWS. PMID- 17281131 TI - Biomimetic coating of apatite/collagen composite on Poly L-lactic Acid facilitates cell seeding. AB - Collagen and apatite were co-precipitated as a composite coating on poly L-lactic acid (PLLA) in an accelerated biomimetic process. The coating formed on PLLA films after 24 hours incubation was characterized. Saos-2 osteoblast-like cells were used to evaluate the cell seeding on this biomimetic composite coating. It was shown that cell seeding on PLLA films with the composite coating was greatly improved. PLLA coated with submicron collagen fibrils and submicron apatite particulates can facilitate bone tissue engineering. PMID- 17281132 TI - Modulation of adhesion and growth of cardiac myocytes by surface nanotopography. AB - We have introduced well-defined nanopillar arrays of polyethylene glycol (PEG) as a platform for studying the adhesion and growth of cultured cardiomyocytes. The nanopillar arrays were fabricated by using a simple molding technique involving the placement of a patterned polyurethane acrylate mold on top of a drop dispensed ultraviolet (UV) curable PEG polymer followed by UV exposure and mold removal. The adhesion and growth of cardiomyocytes turned out be guided by an external nanotopography, which has been characterized in terms of cell morphology and cytoskeletal arrangement. In particular, the nanopillars provided guiding posts to both elongating filopodia and expanding lamellipodia. Interestingly, the 3D growth of cardiomyocytes was mediated by the increased hydrophobicity of the nanostructured PEG substrate, indicating that the cell adhesion and growth is very sensitive to the nanotopography. The precise nanostructures of PEG-based polymer with controlled geometrical features presented in this study not only open opportunities for understanding and tailoring cell adhesion and growth, but could serve as a template for better tissue engineering by controlling cellular activities at the molecular level. PMID- 17281133 TI - Immobilization of gene vector on polyurethane surface using monoclonal antibody for site-specific gene therapy. AB - Conventional strategies of gene therapy using viral vectors result in suboptimal localization and potentially dangerous distal spread of vector. We hypothesized that site-specific delivery of adenoviral gene vectors could be achieved from a polyurethane (PU) film through a mechanism involving anti-viral antibody tethering. PU films were formulated with a collagen coating. Anti-adenoviral monoclonal antibodies were covalently bound to the collagen surface. These antibodies enabled tethering of replication defective adenoviruses through highly specific antigen-antibody affinity. We report for the first time successful PU filmbased gene delivery using antibody-tethered adenovirus encoding green fluorescent protein (GFP), demonstrating efficient and highly localized gene delivery to arterial smooth muscle cells in cell culture. We conclude that PU film is a suitable platform for a localizable viral vector delivery system that also prevents systemic spread of vector. Gene delivery using PU film-based anti viral antibody tethering of vectors should be suitable for a wide array of single or multiple therapeutic gene strategies, and for further stent-based gene delivery therapeutic strategies. PMID- 17281134 TI - Molecularly Engineered p(HEMA)-based Hydrogels Possessing Poly(Ethylene Glycol) and Phosphorylcholine for Implant Biocompatibility. AB - Hydrogels based on 2-hydroxyethyl methacrylate (HEMA) crosslinked with tetraethylene glycol (TEGDA) and molecularly engineered using two methacrylate based monomers, poly (ethylene glycol). PMID- 17281135 TI - Manufacture and characterisation of a bioactive and biodegradable composite developed for bone tissue repair. AB - A bioactive and biodegradable composite containing hydroxyapatite (HA) and polyhydroxybutyrate (PHB) was developed for bone tissue repair. A manufacturing process, which consisted of compounding, pelletising, drying, and injection moulding, was established for producing the composite. The HA/PHB composite containing 10, 20, 30 and 40% by volume of particulate HA was successfully made. The distribution of HA particles in the PHB matrix was examined using scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) was employed to investigate the melting and crystallization behavior of both compounded and injection moulded HA/PHB composite. PMID- 17281136 TI - Spatial patterning of fibroblast cells with fabricating holographic patterning on the photoresponsive polymer. AB - Micro topographic feature was obtained by laser holographic fabrication on the photoresponsive polymer. Surface feature was localized using photomask for developing two dimensional cellular pattering. Fibroblast cells were cultured and proliferated only on the patterned substrate. Obtained cellular pattering suggests that the laser fabricating with photoresponsive polymer would be applied to regenerating new tissue and developing biomedical device of living cells. PMID- 17281137 TI - A Bedside System for Combined RNA and PAC in Heart Failure. AB - Assessment of right ventricular (RV) function is inherently more difficult than left ventricular (LV) function because of the unusual geometry. We have developed a bedside system that integrates a multiwire gamma camera (MWGC) with pulmonary artery catheterization (PAC). This system permits simultaneous acquisition of first pass radionuclide angiography (RNA) images and pressure data from the catheter as well as acquisition of thermodilution data. The system provides highly accurate quantitative measurement of RV and LV ejection fractions, which are indicators of systolic function. This combined RNA-PAC technique permits simple and accurate calculation of both right and left ventricular volume of the ventricular cavity by dividing stroke volume by ejection fraction. Because these data are based on measurements that are non-geometric, this technique for volume measurement is extremely accurate and far surpasses any of the currently available modalities. The system is capable of generating curves relating RV volumes and pressures, which are critical in evaluation of heart failure (HF) patients. Clinical studies were successfully performed on 25 patients, and the results were of high quality and were reproducible. In summary, the system for the first time provides a novel method of generation of RV pressure-volume loops, using a hybrid method of right heart catheterization and RNA. PMID- 17281138 TI - Automated Sleep Staging by a Hybrid System Comprising Neural Network and Fuzzy Rule-based Reasoning. AB - A hybrid system for automated EEG sleep staging is presented in this article. By combining a self-organizing feature map (SOFM) with a fuzzy reasoning-based classifier (FRBC) and utilizing both temporal and spectrum features of the EEG signal, the system provides a reliable tool for automatic EEG sleep staging. Conceptually, the system is divided into four passes: artifact detection, rough staging, stage refinement and post processing. The artifact detection module is firstly employed to exclude stage movement from other stages. Then, the SOFM with features as its inputs derived from the power spectrum divides sleep into three "extreme" stages: Wake, Light/REM and Deep stage. In stage refinement pass, the FRBC, which takes characteristic waveforms' activities as inputs, subdivides the extreme stages into the exact stages (i.e., stage 1, stage 2) defined by R&K standard. At last, in post processing pass, a stage-smoothing method that mainly utilizes the temporal context information is used to correct unexpected stage transitions, thus to improve the system's performance. The system was tested with eight whole night sleep records with an average man-machine agreement of 85.3%. Compared with the high inter-scorer disagreement, the performance is desirable. PMID- 17281139 TI - Quantum resonance spectrometer dynamically monitored sacroma-180 tumor growth in mice. AB - Quantum resonance spectrometer (QRS) was used to dynamically measure quantum effect values (QE values) of immunity, anticancer capacity, cancer cell, and malignant grower in mice inoculated with Sacroma-180 (S-180). Results showed that QE values of immunity and anticancer capacity in S-180 mice were significantly lower than that in healthy mice (p<0.001). Meanwhile, QE values of cancer cells and malignant grower in S-180 mice decreased time-dependently, reached the minimum at the 7thday and returned normal afterwards. In contrast, those two values in healthy mice remained constant during the whole experiments. The results suggested that QRS is a sensitive and scatheless instrument for predicting forepart tumor, but its incapability in identifying anaphase tumor of S-180 in mice remains to be solved. PMID- 17281140 TI - Use of regression equation of peripheral pulse timing characteristics to predict hypertension in children. AB - Studies have shown that an increase in arterial stiffening can indicate the presence of cardiovascular diseases like hypertension. Current gold standard in clinical practice is by measuring the blood pressure of patients using a mercury sphygmomanometer. However, the nature of this technique is not suitable for prolonged monitoring. It has been established that pulse wave velocity is a direct measure of arterial stiffening. However, its usefulness is hampered by the absence of techniques to estimate it non-invasively. Pulse transit time (PTT) is a simple and non-intrusive method derived from pulse wave velocity. It has shown its capability in childhood respiratory sleep studies. Recently, regression equations that can predict PTT values for healthy Caucasian children were formulated. However, its usefulness to identify hypertensive children based on mean PTT values has not been investigated. This was a continual study where 3 more Caucasian male children with known clinical hypertension were recruited. Results indicated that the PTT predictive equations are able to identify hypertensive children from their normal counterparts in a significant manner (p<0.05). Hence, PTT can be a useful diagnostic tool in identifying hypertension in children and shows potential to be a non-invasive continual monitor for arterial stiffening. PMID- 17281141 TI - EEG signal processing in anesthesia-using wavelet-based informational tools. AB - A new tool of wavelet entropy (WE) is applied to characterize the dynamical properties of EEGs for purpose of evaluating the depth of anesthesia (DOA). 31 cases are analysed with WE, and the result shows the WE measure for EEGs can distinguish awake and asleep state in anesthesia with a high accuracy of 95%. Compared with C(n) complexity, the WE demonstrates the same good performance, and needs shorter data length for analysis. These remind that WE is a potential quantifier of DOA. PMID- 17281142 TI - Analysis of water compartment in dengue patients. AB - This paper describes the water compartments in healthy subjects and dengue patients on the day of defervescence of fever using bioelectrical impedance analysis. A total of 223 healthy subjects (65 males and 158 females) and 210 dengue patients (119 males and 91 females) in Hospital Universiti Kebangsaan Malaysia (HUKM), were studied. The ages for healthy subjects vary between 14 and 60 years old with mean age of 26.05 years while the ages for the dengue patients vary between 12 and 83 years old with mean age of 30.14 years. The parameters of water compartments investigated were total body water (TBW), extracellular water (ECW) and intracellular water (ICW). There were significant difference between healthy subjects and dengue patients for both male (p<0.05) and female (p<0.001) beginning on fever day 0 till fever day 4. The mean TBW and ECW values of dengue patients obtained were found to be higher than the normal healthy subjects while the mean ICW was lower. The mean TBW and ICW for male were higher than female while the mean ECW for male was lower than female for healthy subjects and dengue patients. PMID- 17281143 TI - EEG-based Discrimination of Elbow/Shoulder Torques using Brain Computer Interface Algorithms: Implications for Rehabilitation. AB - Brain computer interface (BCI) algorithms are used to predict the torque generation in the direction of shoulder abduction or elbow flexion using scalp EEG signals from 163 electrodes. Based on features extracted from both frequency and time domains, three classifiers are employed including support vector classifier, classification trees and K nearest neighbor. Support vector classifier achieves the highest recognition rate of 92.9% on two able-bodied subjects in average. The recognition rates we obtained on the able-bodied subjects are among the highest compared with previous reports on predicting motor intent using scalp EEG. This demonstrates the feasibility of separating the shoulder/elbow torques using scalp EEG as well as the potential of support vector classifier in applications of BCI. Preliminary experiments on two hemiparetic stroke subjects using support vector classifier reports an accuracy of 84.1% in average, which shows an increased difficulty in predicting intent presumably due to cortical reorganization resulting from the stroke. PMID- 17281144 TI - Mechanisms and rehabilitation of discoordination following stroke using a cortical imaging method. AB - Mechanisms underlying discoordination, expressed in the form of obligatory coupling between the shoulder and the elbow muscles following stroke, are probed by simultaneously recording 163-channel EEG together with elbow/shoulder torques and EMGs from the upper arm. With this unique experimental protocol, we were able to have strict post hoc control of a subject's motor performance. Using this novel approach, this paper provides the first evidence of a linear relationship between an overlap in the cortical activities and obligatory shoulder/elbow torque coupling. Furthermore, results obtained from an 8 weeks multi-degree of freedom isometric training protocol showed that a well-designed treatment intervention could reduce obligatory torque coupling following stroke. Preliminary data indicates that this change in torque coupling appears to be associated with brain reorganization. Other potential rehabilitation methods based on an increased understanding of the mechanisms underlying discoordination following stroke are discussed. PMID- 17281145 TI - Development of a neuroprosthesis for restoring arm and hand function via functional electrical stimulation following high cervical spinal cord injury. AB - This paper describes the development of an implanted neuroprosthesis for restoring hand and arm function to individuals with high level tetraplegia resulting from C1-C4 spinal cord injury. These individuals have complete paralysis below the level of the neck and are thus highly disabled. The neuroprosthesis under development will restore basic upper extremity movements needed for simple yet important daily activities such as eating and grooming. Simulations performed with a musculoskeletal model of the shoulder and elbow indicate that existing stimulation technology using a realistic number of stimulation channels should be sufficient for providing these functions. The neuroprosthesis will utilize 24 channels of stimulation, muscle-based electrodes for stimulation of hand muscles, and nerve cuff electrodes for stimulation of shoulder and elbow muscles. The two implanted stimulators also include a total of four implanted bipolar EMG recording channels that sample activity in neck and facial muscles. These signals, along with measurements of head orientation, will provide the user command interface for this system. PMID- 17281146 TI - Neural plasticity and functional recovery following cortical ischemic injury. AB - Stroke is a leading cause of persistent motor disability, but few effective treatments exist for application at chronic post-injury timepoints. An approach that combines rehabilitative training with cortical electrical stimulation was evaluated in a nonhuman primate model of cortical ischemic stroke. Results indicate that cortical stimulation plus rehabilitation enhanced motor recovery compared to rehabilitation alone. Functional mapping of the spared, peri-infarct motor cortex revealed expansions of motor representations related to the rehabilitative task, with greater expansions for subjects that underwent the combined therapy. It is concluded that electrical stimulation combined with rehabilitation enhanced plastic reorganization of the affected motor cortex, leading to superior behavioral recovery. PMID- 17281147 TI - Wearable health systems and applications: the contribution of information & communication technologies. AB - The interest for wearable health systems originates mainly from the need to extend health services out of the hospital and monitor patients over extensive periods of time. Smart Wearable Health Systems (SWHS) are integrated systems in contact with or near to the body able to sense, (and/or act), process and communicate biomedical and physical parameters. Significant advances in biomedical technology, materials engineering, micro/nanotechnologies and Information and Communication Technologies (ICT) lead to new possibilities for increasing miniaturisation, communication capabilities and system "intelligence". The new possibilities for wearable monitoring are mainly provided at the level of microsensors, wrist and other body worn devices, and smart biomedical clothing. Research and development in these areas has been strongly supported through public funding and private investments worldwide. In Europe the major R&D activities were promoted and supported by the European Commission, Information Society Technologies (IST) programme, mainly through health telematics (telemedicine, e-Health) and micro-nano technologies activities. The aim of these projects was the development and testing of innovative integrated user-friendly systems, environments and scenarios of use that could lead to market exploitation in a short to mid term future (3-5 years). This paper presents the rationale and the results of research on wearable health systems in Europe and comments on the current challenges and futures perspectives in the field. PMID- 17281148 TI - Wearable sensor systems: opportunities and challenges. AB - Sensors are pervasive - from homes to battlefields, and everywhere in-between. Examples include microwave ovens, mobile phones, automobiles, and medical equipment. They have become such an "integral" part of our daily lives that they are not only pervasive but they are also "invisible" to the end-user. These systems are facilitating information processing anytime, anywhere for anyone. While these types of sensors and networks incorporating such sensors are relatively new in the timeline of civilization, there has been one piece of "sensing" technology that has been there since the dawn of civilization. And that is textiles, which, in today's world are indeed pervasive. Textiles (clothing) were initially used for "protection" from the environment - be it from climatic conditions or from other predators as camouflage and personal privacy. This first dimension of "protection" has been complemented by the second dimension of "aesthetics," exemplified by the success of fashion houses in modern times - from Armani to Versace. PMID- 17281149 TI - Towards the development of wearable blood pressure sensors: a photo plethysmograph approach using conducting polymer actuators. PMID- 17281150 TI - Research and applications of virtual medicine. AB - In this paper, we would like to share our experience in developing various virtual medicine applications, including virtual arthroscopy, virtual acupuncture and virtual anatomy. We have deployed the latest graphics processor to develop these virtual reality based learning and training systems. Having utilized various visible human datasets, the visual quality of the applications has been greatly improved. PMID- 17281151 TI - Virtual reality in brain intervention: models and applications. AB - Human body models are key components of VR surgical simulators. We overview here our efforts and share experience in constructing cerebral models and using them in VR-based applications for brain intervention. We have constructed four groups of brain atlases: anatomical, functional, vascular, and physically-based. The atlas-assisted VR systems discussed here are applied to stereotactic and functional neurosurgery, interventional neuroradiology, and brain stereotaxy. We also briefly feature our concept of future surgery. PMID- 17281152 TI - Chinese visible human project: dataset acquisition and its primary applications. AB - The research on digital visible human is of great significance and application value. The US Visible Human Project (VHP) created the first digital image data set of a complete human (one male and one female) in 1995. To promote a worldwide application-oriented VHR, more visible human data sets representative of different populations of the world are in demand. The Chinese Visible Human (CVH) male (created in Oct. 2002) and female (created in Feb. 2003) project achieved greater integrity of images, easier blood vessel identification, and were free of organic lesion. The most noteworthy technical advance of CVH Project was the construction of a low temperature laboratory, which contributed to the prevention of small structures (including teeth, concha nasalis, and articular cartilage) from falling off out of the milling surface. Thus, better integrity of images can be ensured. So far, we have achieved an acquisition of five CVH data sets and the corresponding volume visualization on PC. The 3D reconstruction of some organs or structures has been finished. The work of segmentation on a complete data set is still on-going. PMID- 17281154 TI - Study of Brain Function and Bioenergetics using fMRI and In Vivo MRS at High Fields. AB - The greatest merit of magnetic resonance (MR) methodology applied to medicine is its capabilities of measuring a variety of physiological parameters in vivo. MR imaging (MRI) with unique imaging contrasts can provide vital information which tightly links to brain functions at both normal and diseased states. In contrast, in vivo MR spectroscopy (MRS) is capable of determining metabolites, bioenergetics and chemical reaction rates in brain noninvasively. These capabilities are further enhanced at high/ultrahigh magnetic fields because of significant gain in MR sensitivity and improvements in the spectral resolution of MRS and imaging contrasts. However, MR research also faces many technical challenges which have attracted many scientists from interdisciplinary research backgrounds to find the optimal solutions. Recent progresses in this research field have showed great promise of MRI/MRS for studying brain function, physiology, and neurochemistry. This talk will discuss the developed MR technologies and their applications in brain study at high fields. PMID- 17281153 TI - Virtual reality applications in neurosurgery. AB - Virtual reality technology has great potential to benefit the practice of neurosurgery. Standard 2-dimensional radiologic data of the brain can be transformed into a 3-dimensional virtual object which closely resembles the actual brain, and allows the neurosurgeon to interact it in a realistic manner. By incorporating haptics technology, simulated tactile sensations can also be conveyed to the user. This paper will describe the scope and applications of virtual reality in neurosurgery, especially in the areas of education, training, pre-operative planning and rehearsals. PMID- 17281155 TI - High-resolution Functional Source and Impedance Imaging. AB - Functional imaging has played a significant role in bettering our understanding of mechanisms of brain function and dysfunctions. We review recent research on electrophysiological neuroimaging, multimodal neuroimaging integrating functional MRI with EEG, and our development of magnetoacoustic tomography with magnetic induction for high resolution impedance imaging. Examples from research of our group will be shown to illustrate the concepts. The extensive work being pursued by a number of investigators suggests the promise of functional neuroimaging in imaging neural activity from noninvasive measurements. PMID- 17281156 TI - Functional imaging with MEG and fMRI. AB - The possibility of integrating functional data from magnetoencephalografic (MEG) measurements and functional Magnetic Resonance Imaging (fMRI) offers new insight on the brain organization. In fact, MEG and fMRI integration can provide accurate identification of active brain areas as well as a precise identification of the timing of brain response. In this paper two examples will be discussed: the first aiming at the characterization of the human primary (SI) and secondary (SII) somatosensory cortices, the second concerning how brain reacts to sound coming from different spatial directions. PMID- 17281157 TI - An Improved Algorithm to Extract ERP Component for Brain-Computer Interfaces. AB - In order to improve the communication rates of brain-computer interface(BCI's), scientists are developing appropriate signal processing methods to extract the user's messages and commands from electroencephalograph (EEG). A fast fixed-point algorithm for independent component analysis(FastICA), possesses the advantages of simply structure and fast computation. However, in some cases, many signals are not completely independent, the stability of the algorithm won't be as ideal as people have expected. In fact, the reason that system does not converge steadily is the fixed step size in FastICA algorithm, that is, The negentropy J(wn+1TZ) of random vectors no longer monotonic increasing in the iterative process of separated vectors. We define a cost function δJ=J(wn+1TZ)-J(wnTZ) and a time variant step size μ(t), and put forward a algorithm of adjusting step size by the variety of the cost function in iterative process. Results from a series of simulation and experiments show that, the stability and convergence of algorithm is improved. PMID- 17281158 TI - Dynamic Brain Sources of Single-Trial Auditory Evoked Potentials Data Using Complex ICA Approach. AB - In this study, a robust pre-whitening technique and independent component analysis (ICA) approach are applied to unaveraged single-trial multichannel EEG data from auditory evoked potential (AEP) experiments. Single-trial event-related potential (ERP) data are usually averaged firstly to analysis in order to increase their signal/noise in electroencephalographic (EEG) experiment. However, averaging ignores the trial-by-trial variation of the amplitude. Our approach is based upon the two techniques: decorrelation with a highlevel additive noise reduction and decomposition of individual source components. The results on the unaveraged auditory evoked potential single-trial data analysis illustrate that not only the behavior and location but also the activity strength (amplitude) and dynamics of the individual evoked response can be visualized by the proposed method. PMID- 17281159 TI - Selection of a Subset of EEG Channels using PCA to classify Alcoholics and Non alcoholics. AB - The Principal Component Analysis (PCA) is proposed as feature selection method in choosing a subset of channels for Visual Evoked Potentials (VEP). The selected channels are to preserve as much information present as compared to the full set of 61 channels as possible. The method is applied to classify two categories of subjects: alcoholics and non-alcoholics. The electroencephalogram (EEG) was recorded when the subjects were presented with single trial visual stimuli. The proposed method is successful in selecting the a subset of channels that contribute to high accuracy in the classification of alcoholics and non alcoholics. PMID- 17281160 TI - Spatio-Temporal Clustering of Epileptic ECOG. AB - The spatio-temporal mechanisms underlying the generation of epileptic seizures is not yet clearly understood. In this study, we attempt to quantify the spatio temporal interactions of an epileptic brain by using a previously proposed SOM based Similarity Index (SI) measure. We further show that spectral clustering approach can be appropriately used to determine the average spatial mappings in the brain at different stages of a seizure, by interpreting the SOM-SI values as affinity matrices. Results involving two pairs of seizures of an epileptic patient suggest that there may not be a regular pattern associated with channels's spatio-temporal dynamics during the inter-ictal to prepost ictal transition. PMID- 17281161 TI - Online infomax algorithm and its application to remove EEG artifacts. AB - A online infomax algorithm is proposed in this paper. The performances and properties of this online algorithm is investigated in detail. To the problem of the artifacts removal in real life EEG signal, both the online-and batch infomax algorithm are applied and compared. The experiment results show that the online infomax algorithm proposed in this paper has the good performance both in artifacts removal and convergence in time-varying mixing system. PMID- 17281162 TI - Surface EMG Signal Classification Using a Selective Mix of Higher Order Statistics. AB - We describe a novel application of Higher Order Statistics (HOS) for classifying Surface Electromyogram (sEMG) signals. We have followed seven approaches to identify discriminating signals representative of four primitive motions, i.e., elbow flexion/extension and forearm supination/pronation. The Sequential Forward Selection (SFS) method is utilized to reduce the number of HOS features to a sufficient minimum while retaining their discriminatory information. The SFS selected the kurtosis of sEMG as well as its second order statistics as discriminating features. Our method is robust, and does not require additional computations as compared to existing efficient methods for providing higher rates of correct classification of sEMG, which make it useful in practical sEMG' controlled prostheses. PMID- 17281163 TI - Comparison of the use of approximate entropy and sample entropy: applications to neural respiratory signal. AB - This paper discusses several important factors which can influence the accuracy of the results obtained from application of the well-known Approximate Entropy (ApEn) method and the more recently developed Sample Entropy (SampEn) method to fast neurophysiological signals. Based on the performance of these methods on both computer simulation and experimental data, parameter selection criteria are suggested for application to fast dynamic signals. PMID- 17281164 TI - Respiratory flow estimation from tracheal sound by adaptive filters. AB - In this study, average power of tracheal sound (Pave) was used to estimate flow by parametric method as well as adaptive filters as a nonparametric method. Based on some preliminary studies, an exponential model was used for describing the relationship between flow and Pave for parametric method. It was assumed that flow signal of at least one breath from each target flow is available for calibration. The error for flow estimation with parametric method, was found to be 9 ± 3 % and 10 ± 4 % for inspiration and expiration, respectively. Considering nonparametric method, the estimation error was the least for the third order adaptive filter using the average power of the tracheal sound (dB), which was 10 ± 3 % and 11 ± 4 % for inspiration and expiration, respectively. PMID- 17281165 TI - Robust respiratory flow estimation using statistical properties of tracheal sounds. AB - For any respiratory sound analysis or assessment, respiratory flow must also be measured simultaneously with the sounds. However, due to difficulties and/or inaccuracy of the most flow measurement techniques, several researchers have attempted to estimate flow from respiratory sounds. However, all of the proposed methods heavily depend on the availability of different rates of flow for calibration of the model, which makes their use limited by a large degree. In this paper, a robust and novel method for estimating flow using entropy of the band pass filtered tracheal sounds is proposed. The proposed method is independent of the flow rate chosen for calibration; it requires only one breath for calibration and can estimate any flow rate even out of the range of calibration flow. The method was tested on data of 10 healthy subjects at three different flow rates above 15 ml/s/kg. The estimation error was found to be 7.3 ± 2.0% and 7.4 ± 3.2% for inspiration and expiration phases, respectively. PMID- 17281166 TI - An Incremental Support Vector Machine based Speech Activity Detection Algorithm. AB - Traditional voice activity detection algorithms are mostly threshold-based or statistical model-based. All those methods are absent of the ability to react quickly to variations of environments. This paper describes an incremental SVM (Support Vector Machine) method for speech activity detection. The proposed incremental procedure makes it adaptive to variation of environments and the special construction of incremental training data set decreases computing consumption effectively. Experiments results demonstrated its higher end point detection accuracy. Further work will be focused on decreasing computing consumption and importing multi-class SVM classifiers. PMID- 17281167 TI - Detecting MMN in Infants EEG with Singular Value Decomposition. AB - Mismatch negativity (MMN) is an EEG voltage fluctuation caused by the brain's automatic reaction to unexpected changes in a repetitive stimulation. In an experiment we studied 68 infants of which 2/3 were born preterm. Due to noise of large amplitude, the MMN is difficult to detect in a single infant's EEG. Therefore grand average, which is a average of many subjects EEG recordings, is sometimes used. In this paper singular value decomposition (SVD) is proposed as an alternative to grand average. Consider the SVD USigmaVT = M, where the rows of M contains noisy EEG epochs. Usually data is projected onto the leftmost column of V since this column represent the largest common component of the rows of M. When data is affected by noise of a very large amplitude we may need to choose another column of V. In this paper we propose to choose the leftmost column of V such that the elements of the corresponding column of U has approximately equal values. PMID- 17281168 TI - Transmission-line model for myelinated nerve fiber. AB - Herein, the well-known cable equation for non-myelinated axon model is extended analytically for myelinated axon formulation. The classical cable equation is thereby modified into a linear second order ordinary differential equation with periodic coefficient, known as Hill's equation. Hill's equation exhibits periodic solutions, known as Floquet's modes. The Floquet's modes are recognized as the nerve fiber activation modes, which are conventionally associated with the nonlinear Hodgkin-Huxley formulation. They can also be incorporated in our linear model. PMID- 17281169 TI - Construction of a cardiac conduction system subject to extracellular stimulation. AB - Proper electrical excitation of the heart is dependent on the specialized conduction system that coordinates the electrical activity from the atria to the ventricles. This paper describes the construction of a conduction system as a branching network of Purkinje fibers on the endocardial surface. Endocardial surfaces were extracted from an FEM model of the ventricles and transformed to 2D. A Purkinje network was drawn on top and the inverse transform performed. The underlying mathematics utilized one dimensional cubic Hermite finite elements. Compared to linear elements, the cubic Hermite solution was found to have a much smaller RMS error. Furthermore, this method has the advantage of enforcing current conservation at bifurcation and unification points, and allows for discrete coupling resistances. PMID- 17281170 TI - The Motor Unit Innervation Process Correlation and Its Effects on EMG Applications. AB - It has often been assumed in EMG modeling and signal processing applications, that the Motor Unit Action Potential Trains (MUAPT) of concurrently active motor units during voluntary contractions are not correlated. However, motor unit synchrony, or Motor Unit Innervation Process (MUIP) correlation, which implies MUAPT correlation, has been accepted as a common phenomenon in voluntary contractions. The impact of this MUIP correlation in applications which assume its absence has not been thoroughly studied. In this paper, simulated data with different degrees of MUIP correlation are applied to investigate this issue. Simulation results show that MUIP correlation may compromise the assumption of uncorrelated MUAPTs (depending on recruitment level), and MUIP correlation has a downwards spectrum compression effect on the power spectrum of EMG. PMID- 17281171 TI - Analysis of Transmembrane Potentials Induced by Pulsed Electric Field with Different Durations Based on Five-shelled Dielectric Model of Cell. AB - In order to account for the influence of subcellular organelles on transmembrane potential, five-shelled dielectric model of spherical cell was developed in this paper. And the calculation method of transmembrane potential induced by any pulsed electric field (PEF) was put forward. Thus the effects of different pulse duration on transmembrane potentials of cell membrane and nuclear membrane were also analyzed. It is shown that there is a strong relationship between the amplitude and waveform of transmembrane potential and pulse duration. PEF with shorter duration can reaches into the cell easily, thus with shorter duration pulses, transmembrane potential of nuclear membrane is increasing and close to that of cell membrane. So PEF with shorter duration will bring on some important biological effects, such as electroporation or apoptosis. PMID- 17281172 TI - Simulation analysis of nerve block by high frequency biphasic electrical current based on frankenhaeuser-huxley model. AB - Nerve conduction block induced by high frequency biphasic electrical current was simulated using a lumped circuit model of the myelinated axon based on Frankenhaueuser-Huxley (FH) equations. Axons of different diameters (5-20 μm) can be blocked completed when the stimulation frequency is above 10 kHz. At higher frequency a higher stimulation intensity is needed to block nerve conduction. Larger diameter axons have lower block threshold. The activation of potassium channels, rather than inactivation of sodium channels, is the possible mechanism underlying the nerve conduction block of the myelinated axon induced by high frequency biphasic pulse current. This simulation study, which provides more information about the axonal conduction block induced by high frequency biphasic pulse current, can guide future animal experiments as well as optimize stimulation waveforms for electrical nerve block in possible clinical applications. PMID- 17281173 TI - Classification of homomorphic segmented phonocardiogram signals using grow and learn network. AB - A segmentation algorithm, which detects a single cardiac cycle (S1-Systole-S2 Diastole) of Phonocardiogram (PCG) signals using Homomorphic filtering and K means clustering and a three way classification of heart sounds into Normal (N), Systolic murmur (S) and Diastolic murmur (D) using Grow and Learn (GAL) neural network, are presented. Homomorphic filtering converts a non-linear combination of signals (multiplied in time domain) into a linear combination by applying logarithmic transformation. It involves the retrieval of the envelope, a(n) of the PCG signal by attenuating the contribution of fast varying component, f(n) using an appropriate low pass filter. K-means clustering is a nonhierarchical partitioning method, which helps to indicate single cardiac cycle in the PCG signal. Segmentation performance of 90.45% was achieved using the proposed algorithm. Feature vectors were formed after segmentation by using Daubechies-2 wavelet detail coefficients at the second decomposition level. Grow and Learn network was used for classification of the segmented PCG signals and a classification accuracy of 97.02% was achieved. It is concluded that Homomorphic filtering and GAL network could be used for segmentation and classification of PCG signals without using a reference signal. PMID- 17281175 TI - Study on a mechanical acupuncture instrument with computer aided controlled. AB - Acupuncture relies on the use of fine needles being inserted into specific points with varying amounts of manual or external stimulation. The gate control theory states that acupuncture closes the gate to pain and blocks pain perception in the brain via stimulation of large nerve fibers. The particular research develops a mechanical manipulation of acupuncture to simulate physician with the insertion of acupuncture needles which may produce similar therapy effect. Adopting two stepper motors, the mechanical acupuncture instrument is designed with synthesized movements of lifting, thrusting and twirling. The working process can be controlled by the command strings. The mechanical acupuncture instrument possesses several manipulations of acupuncture just as physician does, and the needle can be adjusted quantitatively and reliably. With quite effective therapy function of animal experiment, the mechanical acupuncture instrument can replace physician to a certain extent. PMID- 17281174 TI - Research on intelligent electroacupuncture technique based on the symbolized measurement theory. AB - This thesis puts forward an intelligent electroacupuncture(EA) technique that imitates traditional chinese medical (TCM) acupuncture technique. In order to solute the difficulty of the fusion between TCM acupuncture technique and engineering technology instruments, the symbolized measurement theory proposed by author has been applied in the imitated approach, which make use of the problem mapping among different domains and scientize the mapping from the TCM acupuncture technique to electric parameter domain. The hardware diagram and the software flow chart of the intelligent acupuncture instrument based on the symbolized measurement theory have been given. PMID- 17281176 TI - Analysis of Body Hair Movement in ELF Electric Field Exposure. AB - For the study of the perception of ELF electric field, a fundamental study was conducted on the movement of body hair in field exposure. The electric force exerted on a hair was given from the force component at dielectric discontinuity. With this force, the equation of the hair displacement in field exposure was derived. The displacement evaluated by the equation agreed well with experimental results. Finally, the hair movement in field exposure was formulated theoretically. The derived equation well describes the real movement of body hair in field exposure. With the equation, the mechanisms of the threshold variation in the field perception was made clear. PMID- 17281177 TI - Research on the measuring and duplication techniques of spectrum of the moxibustion in traditional chinese medicine. AB - Moxibustion has been one of the most important therapeutic methods in traditional Chinese medicine for thousands of years. It is meaningful to research on the mechanism of moxibustion and the techniques about how to realize the perfect efficacy with modern engineering technology. In this paper, the authors presented a series of research works on this, including: experiments on the indirect and direct measuring methods, the first enjoys the advantage of spectrum width, the later is straightforward; studies on the duplication techniques of the spectrum of moxibustion. The main results are: the radiation power of moxibustion is distributed over the region very closed to near-infrared mainly and the wavelength corresponding to the peak value is about 2800 nm; Using tungsten halogen lamp with wide spectral range can duplicate the spectrum of moxibustion by means of light-filtering and power manipulation. A schematic diagram of electric moxibustion which has been used in clinic was also presented. PMID- 17281178 TI - Chronic electrical stimulation of four acupuncture points on rat diabetic neuropathy. AB - The main purpose of this study is to investigate the effects of chronic electrical stimulation of acupuncture points on rat diabetic neuropathy. Diabetes mellitus was induced by a single dose of intravenous streptozotocin. The efficacies of several different protocols of electrical stimulation were compared. The evaluation measures included nerve conduction velocity, tactile threshold and blood perfusion on eye and footpad. Electrical stimulation was administered 30 min/day for 4 weeks. On the 4th weekend of stimulation, when compared with the control group, the stimulated groups showed differential benefits on different evaluation measures. The results indicated that chronic electrical stimulation could reduce the functional deficits of diabetic neuropathy. PMID- 17281179 TI - ICASENSE: Sensitivity mapping using Independent Component Analysis for parallel Magnetic Resonance Imaging. AB - Parallel Magnetic Resonance Imaging (MRI) methods employ receiver coils sensitivities to reduce imaging time: reconstruction algorithms need RF field maps which must be measured or estimated. Assuming statistical independence of different regions in a MR image, we consider the sensitivity estimation as a Blind Source Separation (BSS) problem that can be solved with Independent Component Analysis (ICA). This new formulation permits sensitivity maps extraction from only one MR acquisition, without calibration step or acquisition of additional k-space lines. Simulation results are presented for sensitivity encoded (SENSE) MR images, proving that sensitivity data can be extracted from statistical properties of the image, using the method ICASENSE. PMID- 17281180 TI - A 24-ch Phased-Array System for Hyperpolarized Helium Gas Parallel MRI to Evaluate Lung Functions. AB - Hyperpolarized 3He gas MRI has a serious potential for assessing pulmonary functions. Due to the fact that the non-equilibrium of the gas results in a steady depletion of the signal level over the course of the excitations, the signal-tonoise ratio (SNR) can be independent of the number of the data acquisitions under certain circumstances. This provides a unique opportunity for parallel MRI for gaining both temporal and spatial resolution without reducing SNR. We have built a 24-channel receive / 2-channel transmit phased array system for 3He parallel imaging. Our in vivo experimental results proved that the significant temporal and spatial resolution can be gained at no cost to the SNR. With 3D data acquisition, eight fold (2x4) scan time reduction can be achieved without any aliasing in images. Additionally, a rigid analysis using the low impedance preamplifier for decoupling presented evidence of strong coupling. PMID- 17281181 TI - Study of optimal separation of two circular phased-array coils via an equivalent circuit. AB - The coil separation of phased-array coils is an important issue if a wide area of interest is to be imaged. An equivalent circuit of two circular-shaped coils was used to compute the optimal distance in a two phased-array coil. This circuit included the mutual inductance of two circular coils. An expression for the mutual inductance was derived and the resulting values included in the circuit. With all these elements an equivalent circuit of two overlapped circular coils was built to simulate a phased-array coil. To find a solution to this circuit, specifically written programmes in Spice Opus Light were used. Optimal separations were calculated from separation-vs-attenuation for different coil radii. Results compare very well with those reported in the literature. PMID- 17281182 TI - Using Large Arrays for SNR Improvement on Receiver Limited MRI Systems. AB - Large arrays of RF coils with 16 or more channels are becoming commercially available. However, most MR scanners have eight or fewer receiver channels. In order for these scanners to achieve the SNR benefits of these large arrays, the signals from the array elements must be combined. In this paper, strategies for combining the array elements into 8 or fewer channels are discussed and an analysis of the expected SNR improvement is presented. We expect these results to scale to cases such as 32 channels with 128 array elements. PMID- 17281183 TI - Simultaneous Correction of Intensity Inhomogeneity in Multi-Channel MR Images. AB - Intensity inhomogeneity in MR images is an undesired phenomenon, which often hampers different steps of quantitative analysis such as segmentation or registration. In this paper we propose a novel fully automated method for retrospective correction of intensity inhomogeneity. The basic assumption is that inhomogeneity correction could be improved by combining the information from multiple MR channels. Intensity inhomogeneities are simultaneously removed in a four-step iterative procedure. First, the probability distribution of intensities for two channel images is calculated. In the second step, intensity correction forces, that tend to minimize image entropies, are estimated for every image voxel. Third, inhomogeneity correction fields are obtained by regularization and normalization of all voxel forces, and last, corresponding partial inhomogeneity corrections are performed separately for each channel. The method was quantitatively evaluated on simulated and real MR brain images. The results show substantial improvement in comparison with the two state-of-the-art methods. PMID- 17281184 TI - Removal of Plaque and Stent Artifacts in Subtraction CT Angiography Using Nonrigid Registration and a Volume Penalty. AB - Computed tomography angiography (CTA) is an established tool for vascular imaging. However, high-intense structures in the contrast image can seriously hamper luminal visualisation. This can be solved by subtraction CTA, where a native image is subtracted from the contrast image. However, patient and organ motion limit the application of this technique. Within this paper, a fully automated intensity-based nonrigid 3D registration algorithm for subtraction CT angiography is presented, using a penalty term to avoid volume change during registration. Visual and automated validation on four clinical datasets clearly show that the algorithm strongly reduces motion artifacts in subtraction CTA. Most artifacts disappear, also artifacts caused by minimal displacement of stents or calcified plaques, allowing a 2D and 3D artifact-free visualisation of the vessel lumen. This enables a quick overview of the whole vascular structure and opens the possibility to the visualisation of smaller vessels. PMID- 17281185 TI - Improved Harmonic Phase (HARP) Method for Motion Tracking a Tagged Cardiac MR images. AB - The diagnosis of cardiovascular disease requires precise assessment of both morphology and function of the heart. Currently, magnetic resonance imaging (MRI) provides a useful tool for accurate and reproducible assessment of regional function of the left ventricle noninvasively. MR tagging produces images of the heart that can be analyzed using harmonic phase (HARP) method to describe the regional function of the heart. In order to calculate regional function, a circular mesh is manually built at a specific timeframe, after which the points of such mesh are tracked using the HARP technique. The tracking is not perfect and some individual points on the mesh could fail in tracking. In this work, a new method is presented to improve the tracking by combining HARP with active contour methods. This modified HARP technique is more robust than the previous HARP technique. PMID- 17281186 TI - Correction of intensity inhomogeneity in MR images of vascular disease. AB - We are involved in a comprehensive program to characterize atherosclerotic disease using multiple MR images having different contrast mechanisms (T1W, T2W, PDW, magnetization transfer, etc.) of human carotid and animal model arteries. We use specially designed intravascular and surface array coils that give high signal-to-noise but suffer from sensitivity inhomogeneity and significant noise. We present here a new non-parametric method for correcting the images without assumption of the number of different tissues. Intensity inhomogeneity is modeled with cubic spline and is locally optimized using an entropy criterion. Validation has been performed on a specially design neck phantom as well as actual MR scans on patient neck. This same algorithm has been successfully applied to the correction of very high resolution, intravascular coil images. The steep bias is corrected sufficiently to aid human interpretation of gray scales. It should also make possible computerized tissue classification. PMID- 17281187 TI - Contrast ultrasound methods for left-ventricle ejection fraction measurements. AB - The left-ventricle ejection fraction is an important cardiac-efficiency measure that is regularly used in cardiology. Standard estimations are based on time consuming geometrical analysis and modelling, which requires experienced cardiologists. Alternative methods are very invasive due to the need for cardiac catheterization. In this paper we present and study a minimally-invasive indicator dilution technique for ejection fraction quantification that has recently been developed. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left-atrium and left-ventricle acoustic intensities are recorded versus time by transthoracic echocardiography during contrast bolus passage. The measured curves are corrected for attenuation distortion, filtered to suppress the measurement noise, and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left-ventricle impulse response. The estimated impulse response is interpolated by a mono-compartment exponential model for the ejection fraction assessment. An adaptive search of the interval for the model fitting is also included. The feasibility of the method is tested on 52 measurements in patients with left-ventricle ejection fractions between 10% and 80%. The results are promising and show a 0.83 correlation coefficient with echographic biplane ejection fraction measurements. PMID- 17281188 TI - Ultrasonic imaging of myocardial vibrations associated with coronary artery disease. AB - Coronary artery disease (CAD) is a major cause of majority in the western world. Although progress has been made in recent years for the noninvasive diagnosis of CAD, a widely available, inexpensive and effective diagnostic solution remains elusive. We have developed a novel ultrasound-based technology to detect and analyze the myocardial vibrations associated with diastolic murmurs produced by CAD. Conventional ultrasound imaging systems suppress these vibrations. We have developed algorithms to process the raw ultrasound data and isolate these vibrations and integrated them into a programmable ultrasound system for real time vibration imaging. In preliminary results from clinical studies of patients with CAD, we have observed localized areas of vibrations in the neighborhood of the stenosed coronary artery. The vibrations are narrowband with frequency >200 Hz, and appear to have harmonic components, thus indicating resonance phenomena potentially with nonlinear mechanisms involved. No such vibrations were observed in normal subjects. Analysis of myocardial vibrations could provide a noninvasive diagnostic test for CAD that overcomes many of the limitations of conventional noninvasive tests. Potentially, this technology could provide a new way of evaluating CAD and cardiac function. PMID- 17281189 TI - Average over depth during optical mapping of cardiac propagation. AB - High-resolution optical mapping with voltagesensitive dyes has become a powerful tool to depict complex propagation patterns of cardiac transmembrane potentials. Many studied have proved that this optical signal obtained from tissue surface is the response of the transmembrane potential averaged upon depth rather than only surface. In order to investigate the differentia between the two transmembrane potentials, in this paper, we simulated cardiac propagation using Luo-Rudy (L-R) model and calculated the transmembrance potentials average over depth by an optical decay constant from 0.0 mm to 3.0mm. Our results suggest that the transmembrance potentials weighted average over depth is different from that on the tissue surface, the discrepancy between them depends on the depth of the fluorescence emission of the tissue. If only top layer of tissue (<1.0mm) contributes the fluorescence, optical mapping is an almost accurate representation of surface activation dynamics. PMID- 17281190 TI - Differing effects of cyclosporin a on swelling amplitude and time constant of mitochondria from normal and ischemic rat brain. AB - The purpose of this study was to investigate the effect of cyclosporin A on swelling amplitude and time constant of mitochondria isolated from normal and ischemic rat brain and to observe the possible role of the mitochondrial ATP sensitive potassium channel on mitochondrial permeability transition. Mitochondrial swelling was evaluated by spectrophotometry. Cyclosporin A at 0.5 or 1 microM and diazoxide at 30 microM significantly decreased the swelling amplitude and attenuated the reduction of time constant of mitochondria isolated from normal brain mitochondria induced by 200 microM calcium, an effect abolished by atractyloside at 100 microM. However, cyclosporin A at 5 microM did not affect mitochondrial swelling. In mitochondria from ischemic brain, cyclosporin A at 0.5 microM but not 1 microM significantly decreased mitochondrial swelling amplitude and attenuated the reduction of time constant, which was abolished by atractyloside. Diazoxide had an effect similar to cyclosporin A at 0.5 microM, which was blocked by atractyloside or 5-hydroxydecanoate at 100 microM and 200 microM. Compared with mitochondria isolated from normal brain, those from ischemic brain were more sensitive to cyclosporin A. Activation of the mitochondrial ATP-sensitive potassium channel may be one of the mechanisms by which opening of the mitochondrial permeability transition pore is inhibited. PMID- 17281191 TI - Genetic algorithm for optimization and specification of a neuron model. AB - We present a novel approach for neuron model specification using a Genetic Algorithm (GA) to develop simple firing neuron models consisting of a single compartment with one inward and one outward current. The GA not only chooses the model parameters, but also chooses the formulation of the ionic currents (i.e. single-variable, two-variable, instantaneous, or leak). The fitness function of the GA compares the frequency output of the GA generated models to an I-F curve of a nominal Morris-Lecar (ML) model. Initially, several different classes of models compete among the population. Eventually, the GA converges to a population containing only ML-type firing models with an instantaneous inward and single variable outward current. Simulations where ML-type models are restricted from the population are also investigated. This GA approach allows the exploration of a universe of feasible model classes that is less constrained by model formulation assumptions than traditional parameter estimation approaches. While we use a simple model, this technique is scalable to much larger and more complex formulations. PMID- 17281192 TI - Weak phase-resetting in neural oscillators. AB - Phase-resetting experiments have frequently been employed to understand the input/output dynamics of oscillatory physiological systems, such as the respiratory and cardiovascular systems. Analogous techniques based on phase oscillator models have often been used in computational studies of neuronal networks. These models are often simplified by assuming weak coupling between neurons. This assumption has powerful ramifications for both experimental and theoretical studies, yet it has never been demonstrated in living neurons. Here we examine phase response curves (PRCs) for neurons with different stimulus waveforms. Focusing on amplitude, we show that weak amplitude stimuli create PRCs that scale linearly with amplitude, while strong do not. This is the first step in demonstrating that weak coupling occurs in living neurons. We also show that this notion of weak coupling is more stringent than the geometric classification of weak coupling frequently associated with experimental PRC analysis. PMID- 17281193 TI - A Simple Computational Model for the Estimation of Time-to-collision. AB - It is critical for animals to respond quickly and accurately to avoid looming objects. Recently computation of time-to-collision (TTC) with a looming object have received much attention. TTC can be specified by the optical variable tau ap thetas/thetas', where thetas is the visual angle subtended by the looming object and thetas' is the derivative of thetas over time. The neural mechanisms involved in the computation of tau have been described previously. In this article we describe a neural network model designed to explain the physiological response properties of those tau neurons. We found that 1/tau can be computed by using a weighted combination of 1/(thetas+B) and thetas where B is a constant. We then built a simple computational model by including an improved back propagation algorithm as a way of simulating the brain response patterns. The output of the model is consistent with the performance of the TTC computation. PMID- 17281194 TI - A model of nonlinear motor cortical integration and its relation to movement speed profile control. AB - It is recognized that natural point-to-point movements are characterized by bell shaped speed profiles. However, the neural basis of this smooth, substantially symmetric time course is unknown. Here it is demonstrated via a simplified compartmental model of tufted layer V (TL5) pyramidal neurons, the principal output units of the motor cortex, that nonlinear integration may underlie the bell-shaped profile. Specifically, it is shown that TL5 neuronal output depends upon an approximately multiplicative relationship between inputs to its apical or basal regions (zones A and B, respectively) and those to its central zone (C). This is because the latter facilitate Ca2+dependent bursting that enhances responsiveness to other inputs. As a result, when part of TL5 output returns to zones A and C via thalamocortical and cerebrocerebellar feedback, TL5 neuronal firing rate initially increases before decreasing, rather than progressively decrease as would the output of a linear integrator. This yields a sigmoidal position vs. time response in the musculoskeletal plant and therefore a bell-shaped speed curve. Because of this mechanism, smooth movements may be triggered and modulated by step-like and tonic inputs to zone C as might be received from SMA or basal ganglia. The model thus gives possible insight into the basis of certain features of motor dysfunction in Parkinson's and cerebellar disease. PMID- 17281195 TI - A finite element method based deformable brain atlas suited for surgery simulation. AB - Brain Atlases are valuable tools that assist neurosurgeons during the planning of an intervention. Since current printed and digitalized brain atlas have several disadvantages, including lack of physical descriptions of brain structures and incompatibility with finite element analysis, we have developed a meshed brain atlas for finite element analysis of surgical procedures. Our meshed atlas is a multiple-object FE model integrated with knowledge of mechanical properties of brain tissue with detailed anatomical information. A non-linear hyper viscoelastic mechanical property typically suited for neurosurgery simulation is incorporated. We then partially validated the utility of this model by numerical simulation of a gravity-induced brain deformation scenario. This meshed atlas is able to account for the deformation of both the whole brain and individual structures. It can be applied in large scale finite element simulations and, therefore, offers the possibility of developing bio-mechanical surgical planning and training systems. PMID- 17281196 TI - Development of a shape memory alloy actuator for transanal endoscopic microsurgery. AB - This paper describes problems in traditional transanal endoscopic microsurgery (TEM), and proposes a mechatronics approach in new design. As one of several actuation mechanisms to expose rectal cavity, a compression coil spring made of shape memory alloy (SMA) has been studied. A custom SMA spring actuator was designed to displace 12 mm with 45 N driving force. This actuator was embedded with our new TEM tubular structure and can be used to expose a rectal site up to 60 mm wide and 80 mm long. This exposure is considered to be sufficient for treating many tumors. PMID- 17281197 TI - Orthodontic simulation and diagnosis: an enhanced tool for dentists. AB - We introduce OSD (Orthodontic Simulation and Diagnosis) system, which provides 3 D measurement to the dentists. OSD takes dental casts produced by 3-D scanners as inputs, and simulates what the dentists usually do on the real casts. The cast models are displayed in multiple views, so it is convenient for the user to have a good look from arbitrary positions. Most of the common diagnoses are supported, including tooth size, arch type, Bolton ratio, over bite/jet, Howe's analysis, and also simulated treatment previews. PMID- 17281198 TI - Novel method for registering an endoscope in an operative setup. AB - Calibration and registration of an endoscope are important steps while using the endoscope for any augmented reality applications or for the recovery of 3D information from it during surgical procedures. Traditionally calibration and registration are done simultaneously just before surgery. In this paper we present a novel registration technique, following offline calibration, which is simple, fast and concurs with the ergonomics of an operating room. We are developing a new hybrid navigation system for the purpose of navigation in ventral spine surgeries where in the endoscope is calibrated once in several surgeries, but, it is registered by the proposed novel technique before every surgical procedure. PMID- 17281199 TI - Compute aided diagnosis of facial paralysis based on pface. AB - In this paper, a compute aided diagnosis approach is proposed to physicians in the diagnosis of single-sided facial paralysis. This approach is different from the existing nine subjective and hand-performed international scales such as House-Brackman. For voluntary expressions of a patient, this approach used Pface, which stems from Dface, to measure the asymmetry between two sides of the face. The experiments on test subjects revealed that Pface could differentiate the paralysis stats and normal stats and has the ability of automatic grading facial paralysis. Moreover, Pface of specific face areas can be used in supervision of the rehabilitation process. PMID- 17281200 TI - Real-time Navigation in Orthognathic Surgery. AB - In order to realize real-time navigation in orthognathic surgery, i.e. to realize real-time tracking the pose (position and rotation) of the patient and the instruments, we developed a 3D osteotomy simulation and real-time navigation system (3D OsteoSim&Nav) for the first time in China. After the preoperative 3D simulation, system matches the markers on 3D model to the markers in surgical patient's site to complete the registration. Then the system real-time tracks the pose of the surgical instruments and patient, and real-time offset the site change of the patient. In this way the doctor can accurately operate according to the simulative results. The experimental results show that this navigation system works well and improves the surgical precision. PMID- 17281201 TI - Automated detection and segmentation of diaphyseal bone fragments from registered C-arm images for long bone fracture reduction. AB - Automated identification, pose and size estimation, and contour extraction of diaphyseal bone fragments can greatly improve the usability of a computer assisted fluoroscopy-based navigation system for long bone fracture reduction. In this paper, a two step solution is proposed. The pose and size of a diaphyseal fragment are estimated through 3D morphable object fitting using a parametric cylinder model. The result of fragment identification is then fed to a region information based active contour model to extract the fragment contour. Experimental results show a promising accuracy and robustness of the proposed approach. PMID- 17281202 TI - Transcranial Magnetic Stimulation : Magnetic Field Computation in empty free space. AB - Transcranial Magnetic Stimulation (TMS) is a technique for brain stimulation using magnetic field generated by an external coil. As another techniques like ECT or the implantation of electrodes into motor cortex, TMS has several applications in medical and clinical research. The main benefit of TMS is to be non invasive and painless. TMS use increases but stimulation process remains still empirical and pratician has to perform several stimulations to find the best coil position/direction. We propose to develop a simulator of transcranial magnetic stimulation which aims at computing the electromagnetic field induced in the cortex by TMS. We present in this article the first step of this tool, a parametrical coil model allowing the computation of potential magnetic field outside the head and some way to represent it. PMID- 17281203 TI - Simulation study of detecting conductivity of brain tissues with magnetic induction based on FDTD. AB - To further optimize and improve upon our MIT experiment system, the simulation study of the ideal physical model of our single channel measurement system of MIT is carried out with finite difference time domain (FDTD) method. According to antenna theory, an excitation coil similar to a helix is modeled as a stack of electric and magnetic sources. The current phase deviation of the single MIT channel between the excitation and receiver coils is analysed with three ideal spherical models of the human brain. The brain model considers the skull, the cerebrospinal fluid, the brain tissue and an edema. The phase deviations are calculated for different models when using our coaxial coil system at 10 MHz. When assuming the model without edema the phase deviation of -0.03228712 rad is gotten. The phase deviation of -0.03155229 rad is generated when the spherical edema is considered. PMID- 17281204 TI - Content-Adaptive Finite Element Mesh Generation of 3-D Complex MR Volumes for Bioelectromagnetic Problems. AB - In studying bioelectromagnetic problems, finite element method offers several advantages over other conventional methods such as boundary element method. It allows truly volumetric analysis and incorporation of material properties such as anisotropy. Mesh generation is the first requirement in the finite element analysis and there are many different approaches in mesh generation. However conventional approaches offered by commercial packages and various algorithms do not generate content-adaptive meshes, resulting in numerous elements in the smaller volume regions, thereby increasing computational load and demand. In this work, we present an improved content-adaptive mesh generation scheme that is efficient and fast along with options to change the contents of meshes. For demonstration, mesh models of the head from a volume MRI are presented in 2-D and 3-D. PMID- 17281205 TI - Magnetic resonance electrical impedance tomography of the breast: a simulation study on basic imaging setup. AB - Magnetic resonance electrical impedance tomography (MREIT) has been developed as a new medical imaging modality providing high-resolution conductivity and current density images. This paper is about MREIT of the breast. To show the feasibility of breast MREIT, we carried numerical simulations and breast phantom experiments. We found that an anomaly with 4 mm diameter can be visualized in a reconstructed conductivity image using 5 mA injection current if the SNR of the corresponding MR magnitude image is at least 150. We propose a desirable electrode configuration and show our first experimental results of the breast MREIT. Developing an RF coil for the breast MREIT, we plan to conduct various experimental studies including tissue phantoms. PMID- 17281206 TI - ANN Interpolation in MCG Mapping. AB - Magnetocardiogram is a kind of medical image based on measuring the weak magnetic field of human heart, which reflects the magnetic activity in the human heart, and provides diagnosis information of heart diseases. At present, before visualizing the map based on very limited data, it should be pretreated through interpolation. To gain the high precision, we researched the interpolation in MCG and proposed a new method to solve it - ANN Interpolation. Then we analyzed the performance among ANN Interpolation, Cubic Spline Interpolation and Linear Interpolation. The result is that ANN Interpolation can reach the acquirement. PMID- 17281207 TI - Extraction of motor primitive in consideration of arm posture, movement direction and velocity using Hidden Markov Model. AB - In this paper, we propose a method to extract motor primitives from electromyography(EMG) signals on reaching movements of human arm. EMG signals reflect the motor commands from the central nervous system(CNS). Especially, we extract the motor primitives in consideration of arm posture, movement direction and velocity using only EMG signals. As an experimental task, we performed two kinds of experiments on a horizontal plane, measured ten EMG signals and the hand trajectories during movement. Specially, we extracted motor primitive from the EMG signals during movement by using Hidden Markov Model. Finally, in order to verify how accurately our proposed method divides the motor primitives, we compared the boundary points between the extracted two motor primitives with Via Points that were estimated by using forward and inverse dynamics models. PMID- 17281208 TI - Neural coordination of multijoint stretch reflexes in the human arm. AB - Understanding how stretch sensitive reflexes contribute to the coordination of whole arm posture and movement is best understood in the context of multijoint pertunrbations. However, it is difficult to assess the mechanisms contributing to reflex activity during such unconstrained tasks due to the uncertainties associated with estimating the relative importance of biomechanical and neural coupling between muscles. This study combines experimental and modeling approaches to investigate whether there is significant, neurally-mediated coupling between the muscles of the upper limb. Our data suggest that heteronymous pathways link the actions of muscles spanning multiple joints in the human arm and that these pathways contribute significantly to the reflex responses to perturbations of whole limb posture. PMID- 17281209 TI - Evolution of reflexive and muscular mechanical properties in stroke-induced spasticity. AB - We studied the natural history of reflexive and mechanical properties in hemiparetic spastic stroke subjects. System identification techniques were used to characterize the mechanical abnormalities of the elbow joint and to identify the contribution of intrinsic and reflex stiffness to these abnormalities over one year post-injury. Modulation of intrinsic and reflex stiffness of the elbow joint was studied by applying PRBS perturbations to the elbow at different joint angles at five intervals following stroke. We found that both reflex and intrinsic stiffness were larger in the stroke than in the control arms. They were also strongly position dependent; they both increased with increasing elbow extension but reflex stiffness declined at full extension in some subjects. This position dependency was consistent during stroke recovery. Both intrinsic and reflex abnormally increased over time after stroke. These findings help better understanding of the origins of mechanical abnormalities associated with spasticity and document the time course of these abnormalities during stroke recovery. PMID- 17281210 TI - Towards biomimetic control of a three-link robotic arm in two dimensions. AB - The goal of this work is to explore the control of a robotic arm in a visually guided reaching operation. Considering the role of the superior colliculus and the spinal cord in human arm movements, this paper proposes simple approaches for the control of arm reaching. An efficient use of distance error signals between actual and desired end-point position leads to reaching trajectories in two dimensions that are very similar to more traditional kinematic strategies. This implies that the nature of premotor signals in the spinal cord may be related to simple error signals rather than trajectories. PMID- 17281211 TI - Hierarchical Feedback and Learning for Multi-joint Arm Movement Control. AB - This paper presents a general method for hierarchical feedback control of redundant systems, and applies it to the problem of arm movement control. A high level feedback controller, designed using optimal control techniques, operates on a simplified virtual plant. A low-level controller is responsible for performing a feedback transformation of the physical plant into the desired virtual plant. The method is applied in the context of reaching with two realistic models of the human arm: a 2-DOF, 6-muscle model, and a 7-DOF, 14-muscle model. Simulation results demonstrate the effectiveness of the proposed scheme. PMID- 17281212 TI - Modeling spinal sensorimotor control for reach task. AB - The spinal sensorimotor control system executes movement instructions from the central controller in the brain that plans the task in terms of global requirements. Spinal circuits serve as a local regulator that tunes the neuromuscular apparatus to an optimal state for task execution. We hypothesize that reach tasks are controlled by a set of feedforward and feedback descending commands for trajectory and final posture, respectively. This paper presents the use of physiologically realistic models of the spinal sensorimotor system to demonstrate the feasibility of such dual control for reaching movements. PMID- 17281214 TI - Cardio-respiratory Uncoupling in Congenital Central Hypoventilation Syndrome. AB - Congenital Central Hypoventilation Syndrome (CCHS) is a rare disorder with failure of automatic control of breathing, defined by lack of an appropriate ventilatory response to hypercarbia and hypoxia. However, more detailed evaluation of cardiorespiratory coupling has not been previously performed in those with CCHS. We postulate that those with CCHS have disjointed cardiorespiratory responses to ventilatory challenges due to their alterations in sympathetic modulation. Therefore, we performed ventilatory rebreathing challenges with hypercarbia and hypoxia on 5 subjects with CCHS (age 21.2 ± 5.3 years; 3 females) and 7 controls (age 20.0 ± 4.0 years; 4 females). We measured breath-to-breath respiratory parameters (airflow, PETco2, Sao2), ECG, and continuous non-invasive blood pressure. As previously shown, when compared to controls CCHS subjects lacked ventilatory responses to isocapnic hypoxia (p=0.004) and hyperoxic hypercarbia (p=0.002). During hypercapnia, both control and CCHS subjects had similar rates of decrease in R-R intervals (RRI; slope -1.3 ± 2.5 vs. -1.4 ± 1.1, n.s.) and increase in beat-to-beat averaged blood pressure (MBP; slope 1.2 ± 0.3 vs. 0.4 ± 0.1, n.s.) as PETco2increased. During hypoxia, both control and CCHS groups had similar rates of decrease in RRI (slope 14.2 ± 3.0 vs. 7.5 ± 3.9, n.s.) and increase in MBP (slope -1.11 ± 1.12 vs. -0.9 ± 0.8, n.s.) as Sao2decreased. We conclude that despite having a markedly diminished ventilatory response to hypercarbia and hypoxia, subjects with CCHS have normal cardiovascular responses to these challenges. We speculate that this indicates that chemoreceptors are functional. PMID- 17281213 TI - Biomechanics of the intrinsically optimal design of the intervertebral disc. AB - The spinal shock-absorbing disc needs to have the flexibility to enable the spine to bend and twist. At the same time under loading, its lateral and axial deformations have to be contained, so that it does not herniate and impinge on the spinal-chord. The disc is composed of a fluid-like nucleus pulposus (NP) contained within an annulus. Hence when the disc is loaded, the NP gets pressurized and stresses the surrounding annulus. Now, because its elastic modulus is stress-dependent (i.e. E-E 0 = ksigma, where k is a constitutive parameter ), the annulus stiffens under loading. In this way, the flexible disc is able to sustain its loading with minimal deformation and thereby contain its deformation. In this paper, we have carried out a stress and deformation analysis of the spinal disc, and demonstrated that its deformations are invariant with the load intensity and only dependent on its dimensions and its constitutive property parameter k. Thus, we demonstrate that the intrinsic design of the spinal disc makes it an optimal structure. PMID- 17281215 TI - Noninvasive assessment of cardiovascular autonomic control in pediatric obstructive sleep apnea syndrome. AB - Studies suggest that Obstructive Sleep Apnea Syndrome (OSAS) is causally related to abnormal cardiovascular autonomic control in adults, but this has not been established in pediatric OSAS. The goal of this study was to quantify autonomic system dysfunction, as manifested by cardiovascular response abnormalities, in children with OSAS. During wakefulness, we continuously measured the ECG, arterial blood pressure and airflow in each subject. These measurements were made during the following conditions: spontaneous breathingin the supine posture (baseline), spontaneous breathing in the standing posture (orthostatic stress); tracking of the subject's own prior spontaneous breathing pattern while supine (mental stress), and during a cold face challenge. Using spectral analysis and modeling techniques, we sought to computationally delineate the physiological mechanisms that mediate these abnormalities. Our preliminary results suggest that the autonomic effects of pediatric OSAS differ from those in adult in that parasympathetic activity remains relatively normal despite the elevated peripheral sympathetic drive. PMID- 17281216 TI - A Portable, PC-Based Monitor for Automated, On-line Cardiorespiratory State Classification. AB - We have developed a monitor that acquires, classifies, annotates and displays patient cardiorespiratory data in an on-line and fully automated manner. The monitor is compact, portable and battery-operated; it applies automated methods that detect apnea and classify cardiorespiratory state on-line from non-invasive measurements of patient respiratory movements, blood oxygen saturation and heart rate, logging the raw and processed data. The monitor provides continuous, on line, objective, standardized cardiorespiratory classification and has a graphical display and interface for patient monitoring by a clinician; it has immediate application in the clinical setting. PMID- 17281217 TI - Cardiac autonomic function in older adults with sleep-disordered breathing. AB - We searched for possible associations between various measures of severity of sleep-disordered breathing (SDB) and indices of cardiac autonomic function in older subjects (>60 years). Twenty four overnight unattended home-based polysomnograms obtained from the Sleep Heart Health Study were analyzed using spectral analysis. For each subject, six autonomic indices reflecting heart rate variability were quantitatively determined during wakefulness, REM sleep and non REM sleep. Each individual autonomic marker was regressed against each of 4 measures of SDB, including the respiratory disturbance index (RDI), respiratory oscillation index, cumulative oxygen desaturation, and arousal index. In general, we found no correlation between any of these measures of SDB severity and each of the autonomic indices. However, mean heart rate was found to decrease as RDI increased. As well, the ratio of low-frequency to high-frequency power (LHR) decreased with increasing RDI. Contrary to previous reports, our preliminary findings suggest that sympathetic activity decreases with increasing severity of SDB. This paradoxical association between SDB and cardiac autonomic function may be the result of natural compensatory mechanisms at work, allowing some subjects with SDB to be protected from systemic hypertension or other cardiovascular diseases. PMID- 17281218 TI - Time-Varying Analysis of the Heart Rate Variability during Arousals from Sleep. AB - The goal of this work was to apply a time-varying spectral approach to study the dynamic changes in Heart Rate Variability (HRV) produced by the arousal from sleep in obese patients with and without Obstructive Sleep Apnea (OSA). We studies 10 subjects, group I without OSA and group II with OSA diagnostic. RR intervals series was obtained from ECG records. HRV spectral indexes (HF & LF component) were computed from a time variant AR model. In general, group II has more variability than group I. Results are in agreement with literature for group I. However, group II results don't show statistical differences. Our preliminary results are comparable to others reported. Therefore, this technique allows characterizing transitory phenomena like cardiovascular response to arousals. PMID- 17281219 TI - Elucidating nonlinear baroreflex and respiratory contributions to heart rate variability in obstructive sleep apnea syndrome. AB - Using a Volterra-Wiener model and the Laguerre expansion technique, we estimated in a previous study the parameters that characterize linear and the second order effects of respiration ("RSA") and arterial blood pressure ("ABR") on heart rate. RSA and ABR gains were significantly lower in Obstructive Sleep Apnea (OSA) patients than in normal subjects. During sleep, ABR gain increased in normals but remained unchanged in OSA. In the present work, we investigated the physiological interpretation of the nonlinear components of the described model of heart rate variability, by means of simulation on the computed linear and nonlinear kernels. Our results indicate that the 2ndorder kernels reflect specific characteristics of the RSA and ABR mechanisms, such as a RSA frequency response dependence upon tidal volume, saturation in the ABR-Blood Pressure relation, and respiratory modulation of ABR. PMID- 17281220 TI - Improving prediction of protein subcellular localization using evolutionary information and sequence-order information. AB - Subcellular location of a protein is one of the key functional characters as proteins must be localized correctly at the subcellular level to have normal biological function. In this work, a novel hybrid-classifier prediction method has been introduced, which uses evolutionary information and sequence-order information to improve prediction performance. Prediction results on different data sets show this method performs better or, at least very close to the best existing prediction methods. Further analysis indicates that this hybrid method is also a powerful tool for the prediction of eukaryotic protein subcellular localization. PMID- 17281221 TI - Automated Image Analysis of Fluorescence Microscopic Images to Identify Protein protein Interactions. AB - The identification of protein-protein interactions along with their spatial and temporal localization is vital data for assigning functional information to proteins. Historically, these data sets obtained from fluorescence microscopy, have been analyzed manually, a process that is both time consuming and tedious. The development of an automated system that can measure the location dynamics of the interaction between two proteins inside a live cell is a high priority. This paper describes an automated image analysis system used to identify the interactions between two proteins of interest fused to either GFP or DIV IVA, a bacterial cell division protein that localizes to the cell poles [1]. Upon the induction of DIV IVA fusion protein expression, the GFP-fusion protein will be recruited to the cell poles if a positive interaction occurs. Advanced image processing and feature extraction algorithms are discussed in detail and a statistical feature set used to quantify the image-based information is developed. PMID- 17281222 TI - A novel approach to speed up peptide sequencing via MS/MS spectra analysis. AB - In proteomics, tandem mass spectrometry is the key technology for peptide sequencing from the cells. Different methods have been proposed to sequence peptides through tandem mass spectra. While the methods are capable of providing more robust and accurate results, they are also computationally expensive, and create a bottleneck in high throughput peptide identification. In this work, we introduce a novel approach to speedup peptide sequencing. In contrast to the traditional approaches, we conduct coarse comparison of spectral profiles to drastically shrink the size of candidate peptides. A fast algorithm has been developed for this goal. It is shown in our experiments that such an approach can significantly improve the speed for peptide sequencing. PMID- 17281223 TI - Lattice Monte Carlo simulation of coil-helix transition. AB - An improved self-avoiding lattice model was put forward to study coil-helix transition via dynamic Monte Carlo simulation. Each residue occupies eight simple lattices. By introducing a virtual-imino group and a virtual-carbonyl group, the helical period is not necessarily to be an integer. The Go-like restriction of hydrogen bonding interaction has also been partially released. The coil-helix transition was well reproduced and consistent with the Zimm-Bragg theory. Non native hydrogen bonding interaction seems significant around transition temperature. In characterization of a statistically helical structure, a novel correlation function was put forward and verified. PMID- 17281224 TI - Protein folding dynamics in lattice model with physical movement. AB - We study folding dynamics of protein-like sequences on square lattice by constructing a physically realizable move set that exhausts all possible conformational changes for a structure. By solving the master equation of 16-mer characterized by a 802,075times802,075 transition matrix, we monitor the time dependent probabilities of occupancy of all conformations over 9-orders of time scale from the first kinetic move until reaching Boltzmann equilibrium. We find that folding rates of protein-like sequences adopting the same ground state conformation differ as much as 200 times, and parameters of the native structures, designability, and thermodynamic properties are weak predictors of the folding rates in our model systems. Instead, we show that properties of the kinetic energy landscape defined by the connection graph of physical moves can provide excellent account for observed folding rates. Without the approximation of macrostates, we show how transiently accumulating intermediate states can be identified by basin analysis of the kinetic energy landscape. PMID- 17281225 TI - Expectation Maximization Reconstruction of PET Image with Non-rigid Motion Compensation. AB - Motion artifact degrades PET imaging which often leads to inaccurate quantification of radioactivity concentration. Current motion correction algorithms generally lack the ability to compensate for non-rigid motions as well as perform poorly for frequent non-cyclical motions. In this paper, we derive from first principles a general list mode reconstruction algorithm that accounts for time-varying system responses. We further model the system response function in a way to incorporate the non-rigid motion. The resultant list mode reconstruction algorithm has the ability to compensate for frequent and non-rigid motions, with all detected events utilized. We also provide a histogram reconstruction algorithm that is tailored for gated PET acquisition with reduced usage of computational resource. This algorithm shows good motion compensation capability with computer simulated data and there is no obvious otion artifact visible on the reconstructed image. PMID- 17281226 TI - A computer aided detection system for digital mammograms based on radial basis functions and feature extraction techniques. AB - An intelligent Computer-Aided Detection system (CAD) can be very helpful in detecting and diagnosing breast abnormalities earlier and faster than typical screening programs. In this paper, a system based on Radial Basis neural networks coupled with feature extraction techniques for detecting breast abnormalities in digital mammograms is presented. Suspicious regions are identified following a run of the trained neural network. Within this work, 322 breast images from the MIAS database are considered. Five co-occurrence matrices are constructed at different distances for each suspicious region. A number of statistical features are used to train and test the Radial Basis neural network presented. An average recognition rate of 87% was achieved. Using Receiver Operating Characteristic (ROC) analysis, the overall sensitivity of the technique measured by Az was found to be 0.91. PMID- 17281227 TI - Cone Beam Breast CT with a Flat Panel Detector- Simulation, Implementation and Demonstration. AB - This paper describes our experiences in the simulation, implementation and application of a flat panel detector based cone beam computed tomography (CT) imaging system for dedicated 3-D breast imaging. In our simulation study, the breast was analytically modeled as a cylinder of breast tissue loosely molded into cylindrical shape with embedded soft tissue masses and calcifications. Attenuation coefficients for various types of breast tissue, soft tissue masses and calcifications were estimated for various kVp's to generate simulated image signals. Projection images were computed to incorporate x-ray attenuation, geometric magnification, x-ray detection, detector blurring, image pixelization and digitization. Based on the x-ray kVp/filtration used, transmittance through the phantom, detective quantum efficiency (DQE), exposure level, and imaging geometry, the photon fluence was estimated and used to compute the quantum noise level on a pixel-by-pixel basis for various dose levels at the isocenter. This estimated noise level was then used with a random number generator to generate and add a fluctuation component to the noiseless transmitted image signal. The noise carrying projection images were then convolved with a Gaussian-like kernel, computed from measured 1-D line spread function (LSF) to simulate detector blurring. Additional 2-D Gaussian filtering was applied to the projection images and tested for improving the detection of soft tissue masses and calcifications in the reconstructed images. Reconstruction was performed using the Feldkamp filtered backprojection algorithm. All simulations were performed on a 24 PC (2.4 GHz Dual-Xeon CPU) cluster with MPI parallel programming. PMID- 17281229 TI - Analysis and quantification of arterial wall motion from B-mode ultrasound images - comparison of block-matching and optical flow. AB - Motion of the carotid atheromatous plaque may be responsible for plaque rupture and cerebrovascular symptoms. B-mode ultrasound allows non-invasive recording of arterial wall and plaque motion. Our aim was to analyze quantitatively patterns of arterial wall motion with different techniques. Temporal sequences of digitized B-mode ultrasound images of the carotid arteries of 10 young healthy subjects were interrogated. Arterial wall motion was analyzed using: a/ block matching, and b/ optical flow. The motion of selected regions of the luminal surface of the arterial wall was estimated using region tracking and block matching. The motion of areas of the arterial wall was estimated using optical flow. Waveforms showing radial and axial displacements, as well as radial and axial velocities were produced for the selected ROIs using both techniques. Both techniques produced waveforms with peaks, corresponding to cardiac cycle events, that occurred at similar time points. To study the similarity of the waveforms obtained from the two techniques, a cross-correlation coefficient was calculated. Cross-correlation coefficients were 0.72..0.22 and 0.70..0.19 for displacements and velocities, respectively, in the radial direction. In the axial direction, the coefficients were 0.32..0.39 and 0.24..0.22 for displacements and velocities, respectively. On the basis of this relative comparison of methods, we conclude that significant observations can be made for each motion analysis technique in terms of characterization of the mechanical properties of the tissue. PMID- 17281228 TI - Dynamic cardiac information from optical flow using four dimensional ultrasound. AB - Quantitative analysis of cardiac motion is of great clinical interest in assessing ventricular function. Real-time 3-D (RT3D) ultrasound transducers provide valuable three-dimensional information, from which quantitative measures of cardiac function can be extracted. Such analysis requires segmentation and visual tracking of the left ventricular endocardial border. We present results based on correlation of four-dimensional optical flow motion for temporal tracking of ventricular borders in three dimensional ultrasound data. A displacement field is computed from the optical flow output, and a framework for the computation of dynamic cardiac information is introduced. The method was applied to a clinical data set from a heart transplant patient and dynamic measurements agreed with physiological knowledge as well as experimental results. PMID- 17281231 TI - Imaging detailed glucose metabolism in the brain using MAP estimation in Positron Emission Tomography. AB - In this study, maximize a posterior approach (MAP) was applied for detailed imaging of the glucose metabolism in the brain using PET and 18F-FDG. FDG is a glucose analog and it can investigate a glucose metabolism. In PET studies, glucose metabolism can be measured to estimate a compartment model which describes the behavior of glucose in the brain. We applied the MAP approach to a voxel-by-voxel compartment model estimation in order to visualize a net amount of glucose, glucose transportation, and glucose phosphorylation because a MAP approach is advantageous for robust model estimation against noise existence. When the algorithm was applied to Alzheimer patients, the images had different patterns depending on severity of the disease. We conclude that the proposed MAP based algorithm is useful for detail imaging of glucose metabolism in the brain. PMID- 17281230 TI - Localization and functional parameter reconstruction of suspicious breast lesions by near infrared/ultrasound dual modal imaging. AB - A novel imaging scheme integrating a continuous wave (CW) hand held near infrared tissue imager and a portable ultrasound probe was proposed for evaluation of suspicious breast lesions. A new methodology was developed to reconstruct functional properties of the lesion and the surrounding tissue based on the optical measurement of the diffusive light and the ultrasound measurement of the tumor morphology. The first order Born approximation was used to solve the absorption coefficients for both the tumor tissue and the background tissue assuming that optical properties within each tissue type are uniform. A compression force was applied by the handheld near infrared imager to the breast tissue in order to enhance the optical contrast. The force was monitored by a built-in load cell. 2D projection algorithm was used to find the center of the tumor and to co-register the near infrared image with the ultrasound image. The proposed imaging scheme was tested by a clinical trial where both near infrared and ultrasound data were collected on subjects' breast tissues with embedded suspicious lesions. 3D image algorithm on single patient successfully reconstructed the oxygen saturation and the hemoglobin concentration in both the tumor area and the surrounding tissue. More data collection and analysis are required to confirm this imaging scheme. PMID- 17281232 TI - 3-dimensional brain source imaging by means of laplacian weighted minimum norm estimate in a realistic geometry head model. AB - We investigated the source localization performance of the Laplacian weighted minimum norm (LWMN) estimate technique in a realistic geometry (RG) head model in the present study. We simulated current sources at different brain regions with various noise levels. The present results show there is no obvious depth dependency on the three-dimensional (3D) source estimation. The average source localization error over all simulated cases is about 10 mm. The tangential sources exhibit larger localization errors than the radial sources when they are close to the epicortical surface. The localization error will increase when the noise level increases. The LWMN technique was applied to source imaging of motor potentials induced by finger movement in a human subject. Both activities in the motor and premotor cortex, which are related to the execution and coordinating of the finger movement, were reconstructed by the LWMN technique. The present study suggests that LWMN has great ability in 3D sources imaging. PMID- 17281233 TI - Comparison of different multivariate methods for the estimation of cortical connectivity: simulations and applications to EEG data. AB - The problem of the definition and evaluation of brain connectivity has become a central one in neuroscience during the latest years, as a way to understand the organization and interaction of cortical areas during the execution of cognitive or motor tasks. Among various methods established during the years, the Directed Transfer Function (DTF), the Partial Directed Coherence (PDC) and the direct DTF (dDTF) are frequency-domain approaches to this problem, all based on a multivariate autoregressive modeling of time series and on the concept of Granger causality. In this paper we propose the use of these methods on cortical signals estimated from high resolution EEG recordings, a non invasive method which exhibits a higher spatial resolution than conventional cerebral electromagnetic measures. The principle contribution of this work are the results of a simulation study, testing the capability of the three estimators to reconstruct a connectivity model imposed, with a particular eye on the capability to distinguish between direct and indirect causality. An application to high resolution EEG recordings during a foot movement is also presented. PMID- 17281234 TI - Multi-joint arm movements to investigate motor control with FMRI. AB - Performing multi-joint arm movements in controllable dynamic environments during functional magnetic resonance imaging (fMRI) could provide important insights into the brain mechanisms involved in human motor control and related dysfunctions. In order to obtain useful data, these movements must be possible and comfortable for the subject within the narrow bore of the scanner and should not create any movement artifacts in the image. We found that commonly studied arm movements involving the shoulder create movement artifacts, and investigated alternative multijoint arm movements within a mock-up of an MR scanner. We selected movements involving the elbow and wrist joints, with an extension attached to the hand, and propose a dedicated kinematic structure using the MR compatible actuators we have previously developed. PMID- 17281235 TI - Single-trial analysis of the auditory n100 component. AB - We have recently developed an iterative procedure based on independent component analysis to estimate single trial evoked potentials and used the procedure to analyze data obtained from normal subjects in response to a pure tone, with a whole-head 256-channel recording system. Our results show that new methodology can effectively remove most well-defined artifacts and background activity, and also provide improved estimates of specific components of the evoked potential. With respect to the N100 component, the processed single trials could be separated into two groups, one with trials having the same phase as the average response and another one with trials having the opposite phase, while the number of trials in each group had a very consistent spatial distribution across all subjects. Finally, the sources of the N100 component were primarily due to in phase responses, while the out-of-phase responses had an antagonistic effect. PMID- 17281236 TI - Correlating acupuncture FMRI in the human brainstem with heart rate variability. AB - Past neuroimaging studies of acupuncture have demonstrated variable results for important brainstem nuclei. We have employed cardiac-gated fMRI with T1 variability correction to study the processing of acupuncture by the human brain. Furthermore, our imaging experiments collected simultaneous ECG data in order to correlate heart rate variability (HRV) with fMRI signal intensity. Subjects experienced one of three stimulations over a 31.5 minute fMRI run: (1) electro acupuncture at 2Hz/15Hz over the acupoint ST-36 (2) electro-acupuncture at a sham non-acupoint, or (3) sensory control tapping over ST-36. The ECG was analyzed with power spectral methods for low frequency and high frequency components, which reflect the balance in the autonomic nervous system. The HRV data was then correlated with the time-varying fMRI signal intensity. Our data suggests that fMRI activity in the hypothalamus, the dorsal raphe nucleus, the periaqueductal gray, and the rostroventral medulla showed significant correlation with LF/HF ratio calculated from simultaneous HRV data. The correlation of time-varying fMRI response with physiological parameters may provide insight into connections between acupuncture modulation of the autonomic nervous system and neuroprocessing. PMID- 17281237 TI - A new protein crystallization system with large number of cells. AB - A protein crystallization system with large number of cells for vapor and liquid/liquid diffusion was developed for crystallization of protein and other macromolecules in space. It has high ratio of cell number over system dimension or mass. A facility with it can save the space resource and suitable for boarding of many kinds of spacecraft. PMID- 17281238 TI - Development of a lower body negative pressure box with an environmental control system for physiological studies. AB - A headward fluid shift occurs during microgravity exposure, which causes the cardiovascular adaptive syndrome. Different countermeasures have been proposed to decrease its symptomatology, like the application of lower body negative pressure (LBNP). A LBNP box with an environment control system was developed, aiming to improve features of LBNP boxes used worldwide. It consists of five carbon steel ribs in the shape of a cylinder, which is wrapped with high pressure resistant and transparent vinyl. Inner and outer-wheeled trolleys can comfortably and easily move the subject in and out of the box. A custom-made skirt is secured around the subject's waist by an adjustable belt. The other end is secured between two window-type wooden structures, which seal the LBNP box. Inlet and an outlet valves connect the external to the internal environment of the chamber and tube system allows air to circulate gently. Electronic sensors are used to adjust the airflow keeping a pre-set negative pressure without changing humidity and temperature inside the box. Structural, pressure profile and leaking tests were performed with successful results. The improvements of the present LBNP box have substantially decreased the undesirable side effects of uncontrolled environment conditions during rapid pressure changes, and increased test subjects' comfort. PMID- 17281239 TI - Combining protection of different anti-g techniques to +12 gz: a computer simulation study. AB - The aim of this study is to investigate the upper limit of protection afforded by various protective equipment and techniques that used in combination and used individually. A multi-element, nonlinear mathematical model, which was previously used to produce cardiovascular response to +Gz stress and protection afforded by anti-G suits, was modified by incorporating pulmonary-respiration model, as well as detailed vessel models of abdomen and lower extremities into previous model. Using the model, hemodynamic responses of cardiovascular system to +Gz and to different combination of protection measures were simulated. Simulation results indicate that when appropriate counter-pressure is exerted to lower body, the combination of extended coverage anti-G suit with appropriate positive pressure breathing could provide effortless protection around +9Gz. For higher no-staining protection to +12 Gz, tilt-back seat with angles greater than 55 should be used. It also suggests that for anti-G techniques that enhance +Gz tolerance by means of elevating intrathoracic pressure or increasing blood volume, such as ECGS, PBG, and AGSM, their combined protection may be expressed as an additive sum of their individual effects. However, the combined protection of tilt-back seat with other anti-G techniques is higher than the simple addition. PMID- 17281240 TI - Changes of aortae and pulmonary arteries under simulated microgravity and effects of NOS inhibitor on cardiovascular deconditioning. AB - The present study was to determine the effects of simulated microgravity (SM) on the pulmonary artery (PA) and aorta(TA), and to disclose the changes in pathophysiology of cardiovascular deconditioning(CVD) induced by SM and to explore the effects of NOS inhibitor (N-nitro-L-arginine methylester, L-NAME) on CVD. The high hemodynamics in pulmonary and systemic circulation of human bodies appeared during the initial period and super-regulatory phenomena under 6°head-down tilt bed. PMID- 17281241 TI - Genetic programming artificial features with applications to epileptic seizure prediction. AB - In this paper, we propose a general-purpose, systematic algorithm, consisting of a genetic programming module and a k-nearest neighbor classifier to automatically create artificial features (i.e., features that are computer crafted and may not have a known physical meaning) directly from the reconstructed state-space trajectory of the EEG signals that reveal patterns predictive of epileptic seizures. The algorithm was evaluated in three different patients, with prediction defined over a horizon of 5 minutes before unequivocal electrographic onset. Experiments are carried out using 20 baseline epochs (non-seizures) and 18 preictal epochs (pre-seizures). Results show that just two seizures were missed while a perfect classification on the baseline epochs was achieved, yielding a 0.0 false positive per hour. PMID- 17281242 TI - Decreased Lempel-Ziv complexity in Alzheimer's disease patients' magnetoencephalograms. AB - The aim of the present research is to study the magnetoencephalogram (MEG) background activity in patients with Alzheimer's disease (AD) using the Lempel Ziv (LZ) complexity. We recorded the MEG with a 148-channel whole-head magnetometer (MAGNES 2500 WH, 4D Neuroimaging) in 10 patients with probable AD and 10 age-matched control subjects, during five minutes. Artefact-free epochs were selected for the non-linear analysis. In all MEG channels, the AD patients had lower complexity than control subjects. In 77 of them the differences were statistically significant (p < 0.01). These preliminary results suggest that cognitive dysfunction in AD is associated with a decreased complexity in certain regions of the brain. PMID- 17281243 TI - Brain Source Localization for Two Dipoles Using a Combined Method from 32-Channel EEGs. AB - A problem of estimating biopotential sources in the brain based on electroencephalographic (EEG) signals observed on the scalp is known as an important inverse problem of electrophysiology. Speci A cally, for the inverse problem from EEG data to dipole source there is no unique solution and solutions do not depend continuously on the data. In this paper we describe a system to localize two dipoles to reasonable accuracy from noisy EEG measurements generated by simulating calculation. The system combines backpropagation neural network (BPNN) with nonlinear least square (NLS) method for brain source localization. For inverse problem, the BPNN and the NLS method has its own advantage and disadvantage, so we use the BPNN to supply the initial value to the NLS method and then get the A nal result, here we select the Powell algorithm for the NLS calculating. All these work are for the fast and accurate dipole source localization. The following investigations are presented to show that this combined method used in this paper is an advanced approach for two dipole sources localization with high accuracy and fast calculating. PMID- 17281244 TI - Study on Correlative Dimension of HRV Signals and Its Clinical Applications. AB - In this paper an advanced algorithm based on G-P algorithm is introduced to calculate the Correlative Dimension (CD) of HRV signals. Moreover, Theiler's Correction is considered to avoid the autocorrelation effect of the time serials. It will reduce the possibility to get spurious dimension. The algorithm is applied to clinical HRV data which are collected from twelve young healthy subjects under two conditions: 1) normal state; 2) autonomic nervous system (ANS) being blocked by certain acute selective blocking drug: Atropine or Metoprolol. The result sufficiently shows that the values of CD decrease after blockade, whether Atropine or Metoprolol, is given to the subjects. The reason is that these two kinds of autonomic blocking drug lead to ANS dysfunction. Then the complexity of the heart system decreases. So we can draw a conclusion that the CD value of HRV signals can reflex the complexity of the heart system and the state of ANS. PMID- 17281245 TI - Sleep-stage Characterization by Nonlinear EEG Analysis using Wavelet-based Multifractal Formalism. AB - The wavelet-based multifractal formalism was applied on sleep EEG analysis and sleep-stage characterization. The subjects used in this study were randomly selected from the MIT-BIH Polysomnographic Database. The multifractal singularity spectra of sleep EEG signals were estimated, and h0, the Holder exponent that denotes the main singular property of the signal, was extracted from the multifractal singularity spectrum and used as sleep-stage characteristic parameter. The shift of multifractal singularity spectra of different sleep stage was observed. The mean h0exponents increased from awake to sleep stage 1, 2, 3 and 4, but decreased during rapid eye movement (REM) sleep. Our study suggests that the h0exponent could be used as an important sleep stage characteristic parameter. PMID- 17281246 TI - Application of Artificial Neural Network on Relationship Analysis between Wheat Yield and Soil Nutrients. AB - As a type of nonlinear dynamic parallelism system, artificial neutral network has a capacity of identifying complex causal relationships between variables, such as those between the winter wheat yield and the soil spatial distribution nutrients, including water content, organic matter, total nitrogen, alkali-hydrolysable nitrogen, rapidly available phosphorus and potassium. By training 50 tested soil samples in the back-propagation neutral network of topological structure 6:9:1, the model of analyzing the relation between the crop yield and those 6 soil characteristics was established to validate the remaining 13 samples. The results show that the soil water content and alkali-hydrolysable nitrogen are linear to the crop yield, the total nitrogen, organic matter and rapidly available potassium are respectively multinomial to it and that the rapidly available phosphorous is of the exponential relationship with the crop yield. PMID- 17281247 TI - Study of Rough Set Based Grey Relational BP Neural Network on Grain Yield Forecasting. AB - BP neural network is a nonlinear dynamical system widely-used in forecasting target values influenced by diverse variables. Its redundant input nodes often generate imprecision in the predict results. By introducing rough set and grey relation theories, condition attributes were considered as correlation sequences and decision attributes as reference sequences. The grey correlation coefficients represented the weights upon which the condition attributes were reducted and the initial decision table was renewed with the remaining core factors. As a result of training the network by the reducted condition attributes, the prediction precision was improved prominently. In the model application case to forecast the grain yields of China in 2001 and 2002, the results show great improvement of prediction precision as 0.83% and 1.93%, respectively. And the fitting precision of the grain yields in the other 11 years (1990-2000) are all above 99%. The redundancy elimination also increases the network training rate by reducing the input and hidden nodes. Thus, this optimized model was promising in reducing dimension during knowledge discovery and data dining from a large-scale information pool. PMID- 17281248 TI - Detecting the determinism of EEG time series using a nonlinear forecasting method. AB - The determinism of time series is investigated using a nonlinear non-parametric forecasting method. The goodness of prediction was estimated in terms of the prediction error of the predicted time series. A new definition of the prediction effect was made in the present study. Three typical kinds of time series were detected using our new method. In deterministic chaotic time series, good prediction was obtained in the new definition. However, for Gaussian random noise and schizophrenia EEG signal, the predictability could not found. We concluded that EEGs in schizophrenic patients were not deterministic. PMID- 17281249 TI - A Novel Pitch Period Detection Algorithm Bases on HHT with Application to Normal and Pathological Voice. AB - A modified pitch period detection (MPPD) algorithm is proposed in this paper. It is based on the redefinition of the instantaneous energy density level of Hilbert Huang transform, called as frequency weighted energy density FIE(t). Two examples are employed to illuminate the physical meaning of this new definition. MPPD are used in detection experiments with 78 normal and 70 abnormal vowel /a:/ voices, the experimental results show that MPPD provides more robust performance and makes better results in normal voice pitch detection. PMID- 17281250 TI - Time frequency analysis for transient evoked otoacoustic emissions in different time windows. AB - Transient evoked otoacoustic emissions (TEOAEs) are widely applied in the field of early identification of hearing loss and consequent diagnosis. The duration of testing will not only determine the speed directly but also influence the quality indirectly. In this paper, the default 20ms TEOAEs were divided averagely into 16 continuous 1.25ms-long sub-windows and cross correlation coefficient in each subsection was calculated and compared. Then time-frequency analysis of cone shaped kernel was applied to demonstrate the frequency changes when TEOAEs were processed under different time windows. It is shown that even if the window was reduced to 12.5 ms, high and middle frequency components were hardly affected while the low frequency component was partially impaired. PMID- 17281251 TI - Application of rational power functions in analyses of saccadic velocity profiles. AB - The relationship between the product of peak velocity and duration (VmD) and saccadic amplitude is tightly correlated. The velocity profile of a saccade was referred as a triangular profile; whereas the saccadic amplitude is proportional to VmD. From our observation and derivation, in addition to the triangular profile, the rational power function can also be applied to explain the linear relationship between the saccadic amplitude and VmD. In this study, rational power functions were used for the analyses of saccadic dynamics. The results show that the rational power functions were fitted very well to the velocity profiles for three different amplitudes, i.e. 10deg, 20deg, and 30deg, with correlation coefficients are all greater than 0.99. Significant differences in shape parameters between experimental and simulated profiles were also observed. Additionally, we have found that the minimum variance model proposed based on the minimization of variance of post saccadic eye position cannot simulate velocity profiles matched with the experimental results. In conclusion, rational power functions are efficient in describing the saccadic velocity profiles. The shape parameters are also efficient for describing the dynamics of saccadic velocity profiles. PMID- 17281252 TI - Analysis on the chaotic characteristics of postganglionic inferior cardiac sympathetic nerve activity. AB - Taking cats as experiment animal model, the chaotic characteristics of postganglionic inferior cardiac sympathetic nerve activity (PICSNA) is analyzed with Cao method, correlation dimension analysis and largest Lyapunov exponent analysis. The analysis results show that the deterministic chaos lies in the peak peak interval time series of PICSNA. Our work maybe can help explain why HRV is chaotic. PMID- 17281253 TI - Power-line Interference Removal of Bioelectric Signal Measurement by using Genetic Adaptive Filter. AB - In this study, we proposed a genetic adaptive filter to removing power-line interference. In previous work, the proposed structure, which extracts the interference component from the input biomedical signal to be a reference signal of the adaptive filter to estimate power-line interference, is effective for removing interference. Since this adaptive filter with least-mean square algorithm is sensitive to the eigenvalue spread of the autocorrelation matrix of the reference signals, and the selection of its step-size. Thus, we employ the genetic parallel search technique to improve the least-mean square algorithm. Through simulations, it shows that the adaptive filter with genetic algorithm provides better performance with any step-size. PMID- 17281254 TI - Short term prediction of Ht value using BPNN during LCAP. AB - At present the number of patients of ulcerative colitis(UC) has been increasing in Japan. A leukocytapheresis (LCAP) is one of the cure to the patients of UC. LCAP is a kind of blood purification treatments. It is said that the blood pressure is decreased during the blood purification. This takes place according to the change of the water balance in the body. The water balance is expressed as a hematcrit(Ht) value. Prediction of the Ht value during the LCAP is important to prevent patients from decrease in blood pressure. The purpose of this study is to develop a method to predict the Ht value during the LCAP. In this study, a moving average type back propagation neural network(MANN) is used for analyzing the nonlinear signals. The MANN is one of the suitable methods to analyze biological signals. In this study, Ht values after one minute, three minutes, and five minutes are predicted using BPNN. At first, Ht values are predicted using the various structures of BPNN to obtain precise prediction. PMID- 17281255 TI - Combined neural network model employing lyapunov exponents: internal carotid arterial disorders detection case. AB - This paper illustrates the use of combined neural network models to guide model selection for diagnosis of internal carotid arterial disorders. The method presented in this study was directly based on the consideration that internal carotid arterial Doppler signals are chaotic signals. This consideration was tested successfully using the nonlinear dynamics tools, like the computation of Lyapunov exponents. Statistics were used over the set of the Lyapunov exponents in order to reduce the dimensionality of the extracted feature vectors. The first level networks were implemented for the diagnosis of internal carotid arterial disorders using the selected Lyapunov exponents as inputs. To improve diagnostic accuracy, the second level network was trained using the outputs of the first level networks as input data. The combined neural network models achieved accuracy rates which were higher than that of the stand-alone neural network models. PMID- 17281256 TI - Nonlinear analysis in treatment of intractable epilepsy with EEG biofeedback. AB - About 25% epilepsy patients are suffering from medically intractable epileptic seizure. Many studies have shown that electroencephalogram (EEG) biofeedback therapy has the exciting potential for seizure control. In this paper, five patients with intractable epilepsy were trained to increase the production of sensorimotor (12~15Hz) activity and decrease the production of slow theta (4~7Hz) activity. Nonlinear analysis are proposed to evaluate the effect of biofeedback training. In all the five patients, the complexity and approximate entropy of EEG increased significantly (P<0.05) after (about 1-month) the biofeedback treatment. PMID- 17281257 TI - Recurrence quantification analysis of electrically evoked surface EMG signal. AB - Recurrence Plot is a quite useful tool used in time-series analysis, in particular for measuring unstable periodic orbits embedded in a chaotic dynamical system. This paper introduced the structures of the Recurrence Plot and the ways of the plot coming into being. Then the way of the quantification of the Recurrence Plot is defined. In this paper, one of the possible applications of Recurrence Quantification Analysis (RQA) strategy to the analysis of electrical stimulation evoked surface EMG. The result shows the percent determination is increased along with stimulation intensity. PMID- 17281258 TI - Joint symbolic dynamic analysis of cardiorespiratory interactions in patients on weaning trials. AB - Assessing autonomic control provides information about patho-physiological imbalances. Measures of variability of the cardiac interbeat duration RR(n) and the variability of the breath duration TTot(n) are sensitive to those changes. The interactions between RR(n) and TTot(n) are complex and strongly non-linear. A study of joint symbolic dynamics is presented as a new short-term non-linear analysis method to investigate these interactions in patients on weaning trials. 78 patients from mechanical ventilation are studied: Group A (patients that failed to maintain spontaneous breathing and were reconnected) and Group B (patients with successful trials). Using the concept of joint symbolic dynamics, cardiac and respiratory changes were transformed into a word series, and the probability of occurrence of each word type was calculated and compared between both groups. Significant differences were found in 13 words, and the most significant pn(Wc010, r010): 0.0041 ± 0.0036 (group A) against 0.0012 ± 0.0024 (group B), p-value = 0.00001. The number of seldom occurring word types (forbidden words) also presents significant differences fwcr: 6.9 ± 6.6 against 13.5 ± 5.3, p-value = 0.00004. Joint symbolic dynamics provides an efficient non-linear representation of cardiorespiratory interactions that offers simple physiological interpretations. PMID- 17281259 TI - Linear and nonlinear EEG indexes in relation to the severity of coma. AB - Glascow's coma scale (GCS) is a clinical standard for assessing the severity of coma in intensive care units (ICUs). The EEG monitoring can be on-line work, soon responds to the change in the brain wave, and allows long-term continuous monitoring of brain activity. In this paper, several EEG parameters, including spectral possession distribution and nonlinear description (approximate entropy and Lempel-Ziv complexity) were used to assess the capability of EEG indexes for the severity of coma. Our results demonstrated that all EEG parameters are moderately related to the GCS, with the Spearman statistical correlation of 0.62 0.71 between the spectral possession distribution and the GCS and 0.62-0.66 between nonlinear measures and the GCS. The moderate correlation between EEG parameters and the GCS implies the possibility of the EEG-derived index to reveal the neurological status of patients in coma. PMID- 17281260 TI - Simple electrochemical analysis of enzyme kinetics. AB - Electrochemical sensors enables extremely sensitive measurement of chemical compouns. The measurement and evaluation of enzyme kinetics using electrochemical sensors is presented. The method is implemented in electronic unit OFBio. Theoretical principles are experimentally verified on enzymes glucose oxidasc and acetylcholine esterase. PMID- 17281261 TI - Non linear dielectric properties of microbiological suspensions at electrode electrolyte interfaces. AB - Nonlinear properties of biological suspensions have been previously presented as a bulk phenomenon, however, some authors consider that they are generated at the electrode-electrolyte interface and are reflected as a bulk property phenomenon. They were mainly ascribed to the H+-ATPase present in the plasma membrane of these cells. In this paper, we describe the construction of a dual cell nonlinear dielectric spectrometer. The system is applied to the study of interfaces with resting cell suspensions of Saccharomyces cerevisiae. Substantial harmonics are generated at the interface when a sinusoidal current is applied and altered by the presence of yeast. When a second interface with yeast and enzyme inhibitor is used as reference, a decrease in the magnitude response of the third harmonic can be observed. As it was already described for the solution bulk, we obtained a similar behavior at the interface. Besides, we also found optimal intervals, respectively, for frequency and voltage to reach maximal response. This result would support the contention that biological nonlinearity is an interface-based phenomenon. PMID- 17281262 TI - Test nonlinear determinacy of Electromyogram. AB - To test whether electromyogram (EMG) is nonlinear deterministic signal or just random noise, we analyzed four EMGs data of an adult woman. EMG is assessed with the correlation dimension (D2), maximum Lyapunov exponent (λ1), approximate entropy(ApEn), recurrence plot analysis (RPA) and recurrence quantification analysis (RQA). From all the results of these assessments we can conclude that EMG obeys a certain nonlinear deterministic law and nonstationarity is significant within this signal. PMID- 17281263 TI - Pulse waveforms classification based on wavelet network. AB - This paper proposes a new algorithm to classify pulse waveforms based on discrete wavelet network. This paper selects 4-order discrete Daubechies wavelet as the wavelet node of this wavelet network to classify six pulse patterns distinctive in shape. 600 pulse records are used to train this wavelet network and 300 pulse records are used to test the classifier's performance. The test results show that this approach has 83% agreement rate with the experienced experts. Compared with traditional classification methods, it needs not the experience in feature extraction. PMID- 17281264 TI - Neural network classification of laser-induced 5-ALA-PpIX fluorescence spectra using adaptive principal component extraction. AB - A novel method of feature extraction and classification of fluorescence spectra using neural network was developed in order to improve the diagnostic rate of earlier stage colonic carcinomas with Laser-induced 5-ALA-PpIX fluorescence spectra. 150 min after trail intravenous injections of 5-ALA dose of 25mg/kg body weight (BW) to 40 rats,504 fluorescence spectra excited with 370nm Ti-Laser were collected in vivo, which included 183 normal, 69 dysplasia (DYS), 87 early cancer (EC) and 165 advanced cancer (AC). After preprocessing, 6 principal components were extracted using adaptive principal component extraction (APEX). With BP neural network trained with resilient back-propagation algorithm (RBPNN), all spectra were divided into two categories: normal or abnormal, which included DYS, EC and AC. The sensitivity and specificity were 96.57% and 95.08% respectively. The accuracy of discriminating DYS and EC and AC from normal tissue were 92.75% and 98.85% and 96.36% respectively. The result indicated that this method could effectively diagnose earlier stage colonic carcinomas. PMID- 17281265 TI - Combination of linear and nonlinear methods on electroencephalogram state recognition. AB - Electroencephalogram EEG) reveals brain state, i.e. awake, sleep, rather than the content of thinking. We calculated fast/slow power spectrum ratio and approximate entropy on the EEG of three brain states, normal awake, sleep and coma. Based on the above EEG quantities, the EEG in different brain states can be clearly separated in the following way: (1) fast and complex for normal awake, (2) slow and complex for sleep and (3) slow and simple for coma. PMID- 17281266 TI - Lempel-ziv decomposition based arrhythmic pulses recognition. AB - The computerization of traditional Chinese pulse diagnosis (TCPD) is relatively new in the field of automatic physiological signal analysis and diagnosis. The classification of pulse patterns according to their positions and shapes have been intensively investigated, but until now no research in identifying pulses by their rhythms has been found. This paper introduces a method to distinguish rhythmic and arrhythmic pulse patterns and further, applies the Lempel-Ziv decomposition to classify arrhythmic pulses. In the experiment on 140 clinic pulses, our approach was able to classify pulses by their rhythms with an accuracy of 90.7%. PMID- 17281267 TI - Complexity measure applied to the analysis EEG signals. AB - Electroencephalograms (EEGs) reflect the electrical activity of the brain. The problem of analyzing and interpreting the meaning of these signals has received a great deal of attention. Since EEG signals may be considered chaotic, chaos theory may supply effective quantitative descriptors of EEG dynamics and of underlying chaos in the brain. The complexity of the chaotic system can be characterized by complexity measure computed from the signals generated by the system. The complexity measures include the algorithm complexity of Kolmogorov and C1/C2complexity. This paper gives one new complexity definition of partition algorithm complexity. The experiments proved that the method can distinguish health from diseases. Complexity measure not only provides a new method to analyze EEG signal, but also advances a new idea for diagnosing mental diseases. PMID- 17281268 TI - Nonlinear feature extraction of sleeping EEG signals. AB - This study calculated the spectrum entropy (SE), approximate entropy (ApEn), and Lem-Ziv complexity (LZC) of sleeping EEG signals of eight healthy adults. The statistical results show that all the three nonlinear features can clearly reflect sleeping stage. Among them, the SE is easy to calculate and traces varying sleeping periods fairly and consistently, while the ApEn performs even better but is relatively complicated. The LZC is also simple but loses information details in its preprocessing of original measurement data, which consequently down grades its consistency. Based on a tradeoff of efficiency and efficacy, we consider the SE would be a good feature for real-time tracing sleep stages. Some conclusions are reported based on this study. PMID- 17281269 TI - Hidden markov models and mutual information analysis to characterize nonlinear dynamics in heart rate variability. AB - A study of nonlinear dynamics of the heart rate variability (HRV) was performed using hidden Markov models (HMM) and Mutual Information (MI). A methodology based on HMM has been developed in the present work. Cardiac RR series were analyzed in the three frequency bands: HF (0.15-0.45Hz), high frequency band; LF (0.04 0.15Hz), low frequency band; VLF (0.003-0.04Hz), very low frequency band. These series (0, observations) were modeled using HMM. The model λ=(A,B,∏) was selected so that P(O/λ) was locally maximized. Ergodic topology and N=10 states were also considered for this analysis. Different measures based on HMM were defined and obtained from RR time series of 37 Idiopathic Dilated Crdiomyopathy (IDC) patients and 46 healthy subjects (NRM), during awake and sleep stages. Two groups of IDC patients were considered: 11 high risk (HR) patients, after aborted sudden cardiac death (SCD) or who died during the follow up; 26 low risk (LR) patients, without SCD. Some HMM measures showed high percentages (up to 100%) of well classified subjects in all groups. PMID- 17281270 TI - Predictive models for long term survival after premature rupture of membranes. AB - Premature rupture of the membranes complicates 30 to 40% of the preterm deliveries. The purpose of this study is to assess the outcome of preterm prelabor rupture of the membranes (PPROM) before 26 weeks of gestation and to develop a predictive model for survival. We apply four statistical methods in order to construct a predictive model: Cox's proportional hazards model, logistic regression, least squares - support vector machines and generalized estimating equations. The obtained predictive models are tested on a prospective set and have a very good performance of > 95% for the area under the ROC-curve. PMID- 17281271 TI - EEG-Based Mental Task Classification: Linear and Nonlinear Classification of Movement Imagery. AB - Use of EEG signals as a channel of communication between men and machines represents one of the current challenges in signal theory research. The principal element of such a communication system, known as a "Brain-Computer Interface," is the interpretation of the EEG signals related to the characteristic parameters of brain electrical activity. Our goal in this work was extracting quantitative changes in the EEG due to movement imagination. Subject's EEG was recorded while he performed left or right hand movement imagination. Different feature sets extracted from EEG were used as inputs into linear, Neural Network and HMM classifiers for the purpose of imagery movement mental task classification. The results indicate that applying linear classifier to 5 frequency features of asymmetry signal produced from channel C3 and C4 can provide a very high classification accuracy percentage as a simple classifier with small number of features comparing to other feature sets. PMID- 17281272 TI - Correlation dimensions and entropy of series in electrocardiogram. AB - Heart is one of the most complex dynamic system. Indeed, ECG is important information which reflect the active states of heart. In this paper, select 24 data files of ECG from MIT-BIH database and divide these data into four groups. Series of Rpeaks and RR-intervals extracted from these electrocardiograms are analyzed with the correlation dimension and correlation entropy. The results showed that there are obviously different dynamic characteristics in the four groups. Use the methods of nonlinear dynamics to extract dynamic characteristics from ECG so as to research active states of heart and help doctors clinical application for early diagnose diseases of heart in future. PMID- 17281273 TI - Research of complexity of specific evoked EEG signals. AB - To recognize the specific evoked EEG signals is the popular track in biomedical signal processing. This paper mainly introduced a specific method to recognize the three specific cognitive states. By the way of computing the complexity of the evoked EEG signals, we analyzed the specific thinking-evoked EEG signal and found that there were some significant differences under the three different cognitive states. The differences were mainly located in the complexity of channel C3 and C4. This method provides an effective approach to recognize the three different states and the result of the recognition can be used as the controlling signals for extra usages. PMID- 17281274 TI - Use of ANN and Complexity Measures in Cognitive EEG Discrimination. AB - The purpose of this paper is to apply BP ANN to the discrimination of three kinds of subjects (clinical diagnosed 62 schizophrenic patients, 48 depressive patients and 26 normal controls) respectively in resting state with eyes closed and three cognitive tasks, with EEG complexity measures used as feature vectors. EEG activity is recorded from 16 scalp electrodes and recordings are digitized for off-line processing. Features vectors based on Lep-Ziv complexity and classification with ANN are implemented in Matlab6.5. The comparison between the results of classifying in four states is illustrated and discussed. The classification accuracies achieved are 60% and over. The results show that ANN is an effective approach for discrimination of these three kinds of objects both in baseline and some cognitive states. PMID- 17281275 TI - Complexity Study in Multi-lead Paced ECG Signals. AB - ECG signals have their own inherent orbit as a nonlinear attractor, but for patients with pacemaker, the pacemaker electrical pulse may disturb this natural inherent process and change the natural normal sinus beat ECG attractor. ECG signals of different leads come from the same ECG attractor, they should have the same dimension, whereas it is not true in our experiment. Using nonlinear dynamics techniques such as correlation dimension (CD) can probe the nonlinear property variation of multi-lead ECG. The CDs of 2 leads every 6 second ECG segments from several recordings of MIT-BIH Arrhythmia Database are calculated, including 4 paced recordings. Results show that CDs of different leads ECG signals have significant difference although they come from the same ECG attractors. The paced ECG signals have less complicated properties than normal sinus ECG. PMID- 17281276 TI - Multi-parameter Hopf-bifurcation in HHM Model Exposed to ELF Electric Field. AB - The variation of cell trans-membrane voltage exposed to extremely low frequency (ELF) electric field is analyzed; a modified Hodgkin-Huxley model of muscle (HHM) is established by introducing a new parameter denoting the effect of external electric field, and the bifurcation caused by the new parameter as well as leakage conductance and sodium ions anti-electromotive force is studied. The algebra criterion in high dimension equations is employed to perform the analysis of multi-parameter dynamical bifurcation. The results are of biological significance and suggest that the aberration of dynamics in bio-systems may be accounted for diseases caused by electric exposure. PMID- 17281277 TI - Synthesis of the Growth Hormone Secretion Mechanism Using Nonlinear Analysis and CAD Tools. AB - The goal of this paper is to present a hardware realization of the feed-forward and feedback hypothalamic-pituitary growth hormone (GH) secretion mechanism based on a bio-mathematical nonlinear delay differential equation model developed by Farhy et al. (2003) and Veldhuis et al. (2001). Behavioral modeling is implemented through Verilog hardware descriptive language (HDL) to simulate the antagonistic and stimulatory interaction of growth hormone, growth hormone releasing hormone (GHRH) and somatotropin release inhibiting factor (SRIF). The model is synthesized using computer aided design (CAD) tools and is promulgated through a combinational complex programmable logic device (CPLD)/field programmable grid array (FPGA) Xilinx XSA-50 microchip. The microchip sequentially displays the decimal equivalents of the time changing hormonal concentration levels of the biomathematical model. PMID- 17281278 TI - A QRS Complex Detection Algorithm Based on Mathematical Morphology and Envelope. AB - The QRS complex detection is very important to ECG analysis. This paper aims to present an algorithm of QRS complex detection based on mathematical morphology and envelope. Baseline wandering is removed from ECG signal by morphological method. Then the signal gets the envelope through a low-pass filter, improving signal-to-noise .The performance of the algorithm is evaluated with MIT-BIH database. The algorithm gets the high detection rate (99.79%) and high speed. PMID- 17281279 TI - Detection of DNA with Catalytic Beacons Based on Peroxidase-oxidase Oscillating Reaction. AB - This paper aims at investigating a new method for the detection of DNA with catalytic beacons based on peroxidase-oxidase (PO) oscillation and analytic pulse perturbation technique. Two DNAzymes were constructed by the binding of specific DNA sequence with hemin or by the hybridization of target DNA with the catalytic beacon. Both DNAzymes possessed peroxidase-like activity and perturb the PO oscillator reaction when they were added into the oscillation system. The period and amplitude of oscillation increased significantly by both DNAzymes, which implied the decrease in the average rate of consumption of oxygen in solution, i.e., the decrease of the average rate of NADH oxidation. The results provide a new sensitive method for DNA detection and molecular recognition. PMID- 17281280 TI - Design of sensor node platform for wireless biomedical sensor networks. AB - Design of low-cost, miniature, lightweight, ultra low-power, flexible sensor platform capable of customization and seamless integration into a wireless biomedical sensor network(WBSN) for health monitoring applications presents one of the most challenging tasks. In this paper, we propose a WBSN node platform featuring an ultra low-power microcontroller, an IEEE 802.15.4 compatible transceiver, and a flexible expansion connector. The proposed solution promises a cost-effective, flexible platform that allows easy customization, energy efficient computation and communication. The development of a common platform for multiple physical sensors will increase reuse and alleviate costs of transition to a new generation of sensors. As a case study, we present an implementation of an ECG (Electrocardiogram) sensor. PMID- 17281281 TI - Application of biologically modeled chaotic neural network to pattern recognition in artificial olfaction. AB - This paper presents a novel neural network called KIII model for pattern recognition in artificial olfaction, whose topological structure and parameters are based on anatomical and electrophysiology experiments in mammalian olfactory system. Six data sets of three volatile organic compounds in different conditions, each with a wide range of concentrations, are obtained by a signal acquisition system with tin oxide gas sensor array. They are input into KIII model for training and test. Experimental results show that the system had a good classification performance in a wide concentration range while only a few training samples needed. PMID- 17281282 TI - The feasibility study of the laplacian electrode for EEG. AB - The surface Laplacian can give more localized information of the brain. A concentric bipolar electrode (consisting of a central disc and an outer annulus) can measure the surface Laplacian of the body surface electrical potential distribution. In this article we will study the feasibility of the Laplacian electrode for EEG from the problems of SNR, selection of the electrode parameter. And a new kind of active Laplacian electrode will be introduced to detect the visual evoked potential. PMID- 17281283 TI - A new method of medical robotic device locating and tracking techniques. AB - This work reports on a new and simple method to locate and track the medical robotic device based on the static magnetic field and Hall effort sensor array. In the design, we established a experimental platform based on the static magnetic field and Hall effect sensor array. The platform includes static magnetic source, sensor array module, computer interface and algorithm. The experimental result indicated that this method provides a new way of the medical robotic device locating and tracking. PMID- 17281285 TI - Speech endpoint detection based on speech time-frequency enhancement and spectral entropy. AB - In the process of speech recognition, it is especially crucial to precisely locate endpoints of the input utterance to be free of non-speech regions. This paper proposes a novel approach that finds robust features for endpoint detection in a noisy environment. In this proposed method, we integrate both time-frequency enhancement and the spectral entropy feature. Firstly, the noisy speech is enhanced using spectral subtraction method, in frequency domain to remove the additive noises. Then in time domain, a weight function built by short-time energy and zero-crossing rate is used to remove the noise produced by the spectral subtraction. Finally spectra entropy-based method is used to detect the endpoints. By monitoring the transition of the extracted feature, more precise endpoints could be found. The proposed algorithm is shown to be well suited for the detection of speech endpoint and is very robust for different types of noise, especially for low SNR. Furthermore, the algorithm has a low complexity and is suitable for real-time DSP system. PMID- 17281284 TI - Estimation of Harmonic and Noise Components from Pathological Voice using Iterative Method. AB - The aim of this paper is to analyze and discriminate the pathological voice by separating signal into periodic and aperiodic parts. Separation was performed recursively from the residual signal of voice signal. Based on initial estimation of aperiodic part of spectrum, aperiodic part is decided from the extrapolation method. Periodic part is decided by subtracting aperiodic part from the original spectrum. A parameter HNR is derived based on the separation. Parameter value statistics are compared with those of Jitter and Shimmer for normal, benign and malignant cases. PMID- 17281286 TI - Limitations of ICA for Artefact Removal. AB - This paper reports analysis of the limitations of using Independent Component Analysis (ICA) for biosignal analysis especially artefact removal. The possible difficulty is that there are limited number of electrodes (recordings) making it an overcomplete problem (non-square ICA). The other difficulty is the distribution of biosignal being close to Gaussian. These two properties of the signals may make these outside the standard ICA application. This paper reports that ICA is able to successfully separate the biosignals if the number of recordings are not less than the number of sources. If that is not the case, ICA separates artefact component only when the corresponding artefact is predominant. The experiments demonstrate that the results are not reliable and hence the authors recommend that caution should be exercised before using ICA for such applications. PMID- 17281287 TI - Data fusion of multimodal cardiovascular signals. AB - The electrocardiogram (ECG) is a representative signal containing useful information about the condition of the heart. The shape and size of the P-QRS-T wave, the R-R interval etc. may help to identify the nature of disease afflicting the heart. However, human observer can not directly monitor these subtle details. Hence, the fusion of ECG, blood pressure, saturated oxygen content and respiratory data for achieving improved clinical diagnosis of patients in cardiac care units. Therefore, computer based analysis and display, is highly useful in diagnostics. The study demonstrates the feasibility of fuzzy logic based data fusion of the heterogeneous signals for the detection of life threatening states. Important parameters are derived from multimodal data and rule based approaches have been used. Fuzzified region for various abnormality conditions have been obtained which demonstrate the efficacy of the approach in various test cases. Comprehensive pictures showing the condition of the patient in various states will help physician in making a timely assessment in an intensive care set up. PMID- 17281288 TI - Systematic identification for inert region of a brain from EEG. AB - Evaluation of biomedical signals is important in the diagnosis of neurology diseases, such as dementia, in neurology through the use of electroencephalograms (EEG). While automated techniques exist for EEG analysis, it is likely that additional information can be extracted from EEG signal through the use of new methods. We describe a method for identifying inert region from EEG. This method uses EEG as input to an artificial neural network with five outputs: activity in whole regoin and inert region separated by four regions. PMID- 17281289 TI - The new magnitude-squared coherence functions and their properties sensitive to phase. AB - Based on the core theorem of the frequency domain coherence in signal processing, called as double spectral theorem, we presented the two types of new magnitude squared coherence function (MSCFs) in order to extract the coherence between two signals and gave the conditions that they are equal to 1 or 0. Here, we further studied their properties sensitive to initial phases of two signals and phase difference between two signals. Studying demonstrated that the two type MSCFs not only reflect frequency domain coherence of two signals, but also reflect phase relationship between two signals. One is sensitive to the phase difference between two signals and the other is either sensitive to the initial phases or phase difference between two signals. We call the properties as their properties sensitive to phase. PMID- 17281290 TI - Noise-resistant area integration pulse oximetry. AB - An area integration method of pulse oximetry algorithm is described here suited to oxygen saturation estimation for both low perfusion and movement pulse wave. We remove the base line drift of pulse wave, and integrate the pulse wave of red and infrared separately to remove the noise. It is proven that the ratio of the area is equal to the ratio ac part of pulse wave. We can estimate the SpO2 accurately by this algorithm, and the result of the SpO2 estimation is compared with a golden standard blood gas analysis method. PMID- 17281291 TI - Inductively-coupled control unit for fully implantable middle ear hearing devices. AB - Recently, fully-implantable middle ear hearing devices (F-IMEHD) to enhance the hearing ability of auditory impaired persons have been developed in several countries. The implantable hearing device requires an external controller and a non-invasive power transmitter for recharging an internal battery of the device. This study shows the implementation of an inductively coupled control unit to be able to recharge the battery and transmit a control signal to the implanted device by designing the structure of coupled antennas and the data protocol using an on-off keying modulation. The implemented control unit has the advantages that it makes the implanted device reduce the power consumption and increase a recharging interval by externally supplying the power of a control signal receiver instead of using an internal battery. Through the experimental results, it has been verified that the implemented control unit has the performance of transmitting power and control signal to a F-IMEHD. PMID- 17281292 TI - Tumor Detection in vivo with Optical Spectroscopy. AB - Ultrasound induced blood stasis has been observed for a long time, but to date most experimental observations have been in vitro. In this paper we discuss a possible diagnostic use for this previously undesirable effect of ultrasound - tumor detection in vivo. We demonstrate that, using optical spectroscopy, effects of ultrasound can be used to differentiate tumor from non-tumor in murine tissue. Finally, we propose a novel diagnostic algorithm that quantitatively differentiates tumor from non-tumor with maximum specificity 0.83, maximum sensitivity 0.79, and area under ROC curve 0.90. PMID- 17281293 TI - Data management system for computer aided biophysical monitoring. AB - The Data Stream Management System designed to be applied in medical monitoring systems is presented. Such approach simplifies the structure of the monitoring system. Communication between management and monitoring systems is based on the formal query language. The developed theory and query language is adapted to specific requirements of the signal processing in biophysical monitoring systems. PMID- 17281294 TI - Hybrid Progressive Algorithm to Recognize Type II Diabetic Based on Hair Mineral Element Contents. AB - In this paper, a hybrid progressive algorithm to recognize type II diabetic based on hair mineral element levels is proposed. Hair samples of 244 cases (Table 1) are collected from 51 healthy persons (one case each person), 47 unchecked diabetics (one case each person) and 73 checked diabetics (two cases each person). 8 hair elements (Mg, Ca, Fe, Cu, Zn, Se, Cr and Mn) are measured. The hybrid progressive algorithm is used to form a scalar quantity (dynamic diagnosis index (DDI)) based hair element levels. The result show that hair may be a good symptom index to judge whether a person affected by diabetes mellitus if appropriate sampling and measuring procedure adopted and proper algorithm to retrieve information from multi-elements levels in hair. Because the non-invasive characteristics of hair analysis, this procedure and algorithm is very suitable at least to large population screening of early diabetes. PMID- 17281295 TI - Real-time Physiological Emotion Detection Mechanisms: Effects of Exercise and Affect Intensity. AB - The development of systems capable of recognizing and categorising emotions is of interest to researchers in various scientific areas including artificial intelligence. The traditional notion that emotions and rationality are two separate realms has gradually been challenged. The work of neurologists has shown the strong relationship between emotional episodes and the way humans think and act. Furthermore, emotions not only regulate human decisions but could also contribute to a more satisfactory response to the environment, i.e., faster and more precise actions. In this paper an analysis of physiological signals employed in real-time emotion detection is presented in the context of Intelligent Inhabited Environments (IIE). Two studies were performed to investigate whether physical exertion has a significant effect on bodily signals stemming from emotional episodes with subjects having various degrees of affect intensity: 1) a statistical analysis using the Wilcoxon Test, and 2) a cluster analysis using the Davies-Bouldin Index. Preliminary results demonstrated that the heart rate and skin resistance consistently showed similar changes regardless of the physical stimuli while blood volume pressure did not show a significant change. It was also found that neither physical stress nor affect intensity played a role in the separation of neutral and non-neutral emotional states. PMID- 17281296 TI - Double Spectral theorem and Two Type Magnitude Coherence Functions. AB - Studying frequency domain representation for the coherence between two signals is an important basic theoretical problem in the fundamental theories of signal processing. However, magnitude-squared coherence function (MSCFs) could lose some phase information. Based on the core theorem in the frequency domain coherence theories, called as double spectral theorem (DST), we presented the two types of new magnitude coherence functions (MCFs), called as the same type magnitude coherence function (SMCF) and the difference magnitude coherence function (DMCF) respectively, which had been mathematically derived from DST and the conditions that they are equal to 1 or -1 or 0 were theoretically derived from DST. Here, we further demonstrated that SMCF and DMCF could be used to exactly extract the coherence between two signals by each component. PMID- 17281297 TI - The new magnitude coherence functions and their properties sensitive to phase. AB - Because magnitude-squared coherence function (MSCFs) could lose some phase information, based on the core theorem for the frequency domain coherence in signal processing, called as double spectral theorem, we present the two types of new magnitude coherence functions (MCFs) in order to extract the coherence between two signals and give the conditions that they are equal to 0 or +1 or -1. Here, we further study their properties sensitive to initial phases of two signals and phase difference between two signals. Studying demonstrated that the two type MCFs not only reflect frequency domain coherence of two signals, but also reflect the phase relationship between two signals. One is sensitive to the phase difference between two signals and the other is either sensitive to the initial phases or the phase difference between two signals. We call the properties as their properties sensitive to phase. PMID- 17281298 TI - Recovery of Metabolomic Spectral Sources using Non-negative Matrix Factorization. AB - 1H magnetic resonance spectra (MRS) of biofluids contain rich biochemical information about the metabolic status of an organism. Through the application of pattern recognition and classification algorithms, such data have been shown to provide information for disease diagnosis as well as the effects of potential therapeutics. In this paper we describe a novel approach, using non negative matrix factorization (NMF), for rapidly identifying metabolically meaningful spectral patterns in1H MRS. We show that the intensities of these identified spectral patterns can be related to the onset of, and recovery from, toxicity in both a time-related and dose-related fashion. These patterns can be seen as a new type of biomarker for the biological effect under study. We demonstrate, using k-means clustering, that the recovered patterns can be used to characterize the metabolic status of the animal during the experiment. PMID- 17281299 TI - A general recurrent neural network approach to model genetic regulatory networks. AB - There is an urgent need for tools to unravel the complex interactions and functionalities of genes. As such, there has been much interest in reverse engineering genetic regulatory networks from time series gene expression data. We use an artificial neural network to model the dynamics of complicated gene networks and to learn their parameters. The positive and negative regulations of genes are defined by a weight matrix, and different genes are allowed to have different decaying time constants. We demonstrate the effectiveness of the method by recreating the SOS DNA Repair network of Escherichia coli bacterium, previously discovered through experimental data. PMID- 17281300 TI - Discovering drug mode of action using reverse-engineered gene networks. AB - A major challenge in drug discovery is to distinguish the molecular targets of a bioactive compound from the hundreds to thousands of additional gene products that respond indirectly to changes in the activity of the targets. Here, we present an integrated computational-experimental approach for computing the likelihood that gene products and associated pathways are targets of a compound. This is achieved by filtering the mRNA expression profile of compound-exposed cells using a reverse-engineered model of the cell's gene regulatory network. We apply the method to a set of 6 whole-genome Escherichia coli expression profiles at different time points after treatment with the antibiotic Norfloxacin. We show that the algorithm can correctly identify the known drug targets and associated pathways. PMID- 17281301 TI - Peptides design based on the interfacial helix of integrase dimer. AB - HIV-I integrase (IN) plays a crucial role in the retroviral life cycle. The peptides derived from the helix of IN were reported to have the potency of inhibition. We designed a series of peptides based on interface helices alpha1 and alpha5 with the aim of increasing their inhibitory activity. The helix forming tendency and the affinity with IN were essential for interfacial peptide inhibitors. The MD simulation and AGADIR prediction both showed favorable results for the designed peptides. The binding mode and binding free energy of peptide and IN were investigated subsequently to test our design. The improvement in binding free energy compared with that of alpha1 and alpha5 indicates that some of the designed peptides may have a higher potency for inhibiting the dimerization of IN. This study provides some useful information for rational design of IN peptide inhibitor. PMID- 17281302 TI - Research on the quantitative structure-carcinogenic activity relationship of N nitroso compounds. AB - According to the results of quantitative pattern recognition for 153 N-nitroso compounds (NNCs) based on Di-region theory, it is put forward that the esters formed from the metabolism of NNCs on ..- or ..-position could be alkylating agents of DNA bases with the anchimeric assistance of the N-nitroso group. This viewpoint, combined with the conception of ..-metabolism activation, can explain the structurecarcinogenic activity relationship reasonably. Quantum chemistry ab initio calculations are carried out to study the activity of different metabolites of NNCs in direct alkylation and the anchimeric assistant processes. By ONIOM method, a QM/MM calculation is carried out to study the crosslink of DNA base pair by methylalkylnitrosamines. Based on the computational results, the quantitative structure and carcinogenic activity relationship of 58 N nitrosoureas that have got animal carcinogenicity tests reported are studied. PMID- 17281303 TI - Study on Relationship between Protein Sequence Pattern and Protein Secondary Structure. AB - In this paper, the relation between protein sequence pattern and protein secondary structure is studied deeply. It first introduces the protein sequence pattern and organism-specific dictionary. Then four effect factors that may affect the secondary structure of protein sequence pattern are presented. One of the factors, protein sequence segment that matches the pattern is analyzed in detail. Amino acid effect on secondary structure and effect vector are defined for the first time. Finally, the secondary structure prediction method based on the effect vector is proposed. Experimental result shows that the effect of amino acid residues on secondary structure is both position-specific and structure specific. Amino acid effect vector is important and effective in secondary structure prediction for patterns or proteins. The prediction accuracy rate can reach 80.2% for patterns with similar secondary structures. PMID- 17281304 TI - Prediction of the binding model of HIV-1 gp41 with small molecule inhibitors. AB - Despite the synthetic peptides inhibit HIV-1 entry; its application of this peptide therapy may be limited due to the high cost of the peptide production and lack of its oral availability. Thus, it is necessary to identify the small molecule inhibitors reacting with the same or overlapping target sites on gp41 recognizing the antiviral peptides. In this work, a small inhibitor (TP1) is docked into the hydrophobic grooves of gp41 by using AutoDock software, resulting in five alternative energetically favorable models. The data from other studies were used to define our preferred models. We found that only one binding mode is supported by the experimental evidence. The model could be used to design more effective HIV-1 inhibitors targeted to the HIV-1 gp41 core structure. PMID- 17281305 TI - A Structural Data Mining Approach for the Classification of Secondary RNA structure. AB - There exist many methods for classifying genomic data by aligning, comparing, and analyzing primary nucleotide sequences using such algorithms as dynamic programming and kinetic folding, etc.. These methods are, however, not always effective as motifs are more conserved in structures than in sequences. Instead of performing classification based on primary sequences, we therefore propose to perform the task from structure, exploiting the phenomenon in which molecules form from a sequence of nucleotides, beginning with a primary sequence that can fold back onto itself to form a secondary structure and then a tertiary structure. The algorithm we propose is able to perform data mining in structural data and is called the Random Multi-Level Attributed (RMLA) graph algorithm for mining and representing secondary genomic structure from such biomolecule as tRNA. The identification of structural similarity is implemented with information measure concept to characterize the resultant class. Experiments are based on known tRNA structural data from database of compilation of tRNA genes. The results show that our approach is able to effectively classify different class of tRNA secondary structure. We also compare our result with other classification algorithms to prove the effectiveness. Our approach shows a better way to classify structural data. In fact, RMLA graph is not suitable only for the classification of genomic data, wherever graphs are used to model data, it is useful for discovering patterns in the databases. PMID- 17281306 TI - Multiple gene order alignment. AB - Multiple alignment of genomic sequences have been studied in the past [1]. The focus of early works has been on pair wise and multiple alignment of individual genes. More recent works have studied the pair wise and multiple alignment and rearrangement of gene order sequences [2], [3]. The previous approaches to gene order analysis were largely based on break-point analysis or gene rearrangements. We describe an algorithm for alignment of gene order sequences based on a graph based consensus method. The algorithm can be applied to align 2 or more gene order sequences and obtain the ancestor gene order sequence. The algorithm argues for a potentially simpler approach for multiple alignment of gene orders based on a notion of precedence. The algorithm can also be implemented in parallel to further increase its speed. PMID- 17281307 TI - Functional site analysis in proteins of g protein signaling pathways using fuzzy evolutionary trace method. AB - GPCRs are physiologically significant receptors linked to numerous diseases including cardiovascular disease, mental illness, and cancer. Inhibiting the interaction between a GPCR and its G-protein blocks the ability of the receptor to initiate a signal in a cell. G Protein active sites control nearly all G protein functions and determine the interactions upon which G protein signaling pathways are built. Characterization of the active sites in G protein or GPCRs would therefore lead to new methods of controlling G proteins and ultimately controlling cells. This paper use fuzzy evolutionary trace method to analyze the binding sites of G Protein and finally give an example. PMID- 17281308 TI - Molecular Diagnosis and Biomarker Identification on SELDI proteomics data by ADTBoost method. AB - Clinical proteomics is an emerging field that will have great impact on molecular diagnosis, identification of disease biomarkers, drug discovery and clinical trials in the post-genomic era. Protein profiling in tissues and fluids in disease and pathological control and other proteomics techniques will play an important role in molecular diagnosis with therapeutics and personalized healthcare. We introduced a new robust diagnostic method based on ADTboost algorithm, a novel algorithm in proteomics data analysis to improve classification accuracy. It generates classification rules, which are often smaller and easier to interpret. This method often gives most discriminative features, which can be utilized as biomarkers for diagnostic purpose. Also, it has a nice feature of providing a measure of prediction confidence. We carried out this method in amyotrophic lateral sclerosis (ALS) disease data acquired by surface enhanced laser-desorption/ionization-time-of-flight mass spectrometry (SELDI-TOF MS) experiments. Our method is shown to have outstanding prediction capacity through the cross-validation, ROC analysis results and comparative study. Our molecular diagnosis method provides an efficient way to distinguish ALS disease from neurological controls. The results are expressed in a simple and straightforward alternating decision tree format or conditional format. We identified most discriminative peaks in proteomic data, which can be utilized as biomarkers for diagnosis. It will have broad application in molecular diagnosis through proteomics data analysis and personalized medicine in this post-genomic era. PMID- 17281309 TI - Selecting differentially expressed proteomic markers from mass spectrometry data. AB - High-throughput mass spectrometry and statistical analysis methodologies are promising technologies to aid the medical diagnostics field by detecting the cancer-related proteomic markers. We propose statistical methods to cull the potential markers by ranking them in relations to their power of separability distinguishing cancerous patients from normal persons or among different cancer stages. To assess the training variability, resampling via bootstrap strategy is adopted to select stable markers which show the potential of a large probability to classify specific groups. Selected marker pattern is validated by a combined classifier. Methods are demonstrated by a colon cancer dataset screened by SELDI technology. PMID- 17281310 TI - Assessing the codetermination of gene transcriptional States using both superscalar and vector multiple processor systems. AB - An important goal of functional genomics is to develop methods for determining ways in which individual actions of genes are integrated in the cell. One way of gaining insight into a gene's role in cellular activity is to study its expression pattern in a variety of circumstances and contexts, as it responds to its environment and to the action of other genes. Microarrays provide large-scale surveys of gene expression in which transcript levels can be determined for thousands of genes simultaneously. The coefficient of determination (CoD) has been proposed for the analysis of gene interaction via multivariate expression arrays. Parallel computing is essential to the application of the CoD to a large set of genes because of the large number of expression-based functions that must be statistically designed and compared. The results of the calculation of the CoD for a large set of genes with multiple superscalar processors are presented. A proposal for calculating the CoD with multiple vector processors is described. Multiple vector processor systems offer the potential to greatly reduce the time to calculate the CoD for a large set of genes. PMID- 17281311 TI - Multifractal Analysis of Genomic Sequences CGR Images. AB - To describe the fractal feature of Chaos Game Representation (CGR) images of genomic sequences, a multifractal theory is presented in the analysis. With the probability set of CGR images, the general dimension spectrum and the multifractal spectrum are calculated and compared between two sample groups of gene thick sequences and gene black sequences. The experimental result shows that the probability set composed of the relative probability has the best scale invariance performance. The scale invariance has different variance regions, which indicates genomic sequence segments with different lengths have different distribution rules. It is also shown that the sequences, spectra for two groups are different, specially the attenuation index and value range of the general dimension spectrum, and the width of the multifractal spectrum. It is concluded that the mutifractal analysis and its parameters may be useful to analyze sequences's statistic property and recognize gene sequence. PMID- 17281312 TI - The Correlation between Recombination Rate and Codon Bias in Yeast Mainly Results from Mutational Bias Associated with Recombination Rather than Hill-Robertson Interference. AB - Codon usage has been reported to be correlated with local recombination rate, which can be explained by two proposed models. In the present study, correspondence analysis was used to investigate the major trends in codon usage variation among S. cerevisiae genes. It was found that the first principle source of codon usage variation in yeast is due to the variance of expressional levels, which is consistent with the previous translational selection model. Moreover, recombination rate is also correlated with the codon pattern, which might be a byproduct of mutational bias associated with recombination rather than the consequence of Hill-Robertson interference. A recent study has analysed the genome sequence, but reached opposite conclusions: the positive correlation between recombination rate and codon bias in yeast mainly results from Hill Robertson interference. In light of this conflicting result, we have discussed the possible reason and found that the previous analysis was undermined by mistaken assumptions that weak selection acting at expression level led to the correlation between recombination and codon bias. PMID- 17281313 TI - Prediction Models for DNA Transcription Termination Based on SOM Networks. AB - This paper presents two efficient models for predicting transcription termination (TT) in human DNA. A neural network, self-organizing map, was used for finding features from a human polyadenylation (polyA) sites dataset. We derived prediction models related to different polyA signals. A program, "Dragon PolyAtt", for predicting TT regions was designed for the two most frequent polyA sites "AAUAAA" and "AUUAAA". In our tests, Dragon PolyAtt predicts TT regions with a sensitivity of 48.4% (13.6%) and specificity of 74% (79.1%) when searching for polyA signal "AAUAAA" ("AUUAAA"). Both tests were done on human chromosome 21. Results of Dragon PolyAtt system are substantially better than those obtained by the well-known "polyadq" program. PMID- 17281314 TI - Study of HIV Variability based on Genomic Signal Analysis of Protease and Reverse Transcriptase Genes. AB - The conversion of genomic sequences into digital genomic signals offers the possibility to use signal processing methods for the analysis of genomic information. The study of genomic signals reveals local and global features of chromosomes that would be difficult to identify by using only the symbolic representation used in genomic data bases. The paper presents a study of the HIV Protease (PR) and Reverse Transcriptase (RT) genes by combining standard nucleotide sequence analysis with IT techniques based on the genomic signal approach. Cumulated and unwrapped phases of genomic signals are analyzed to characterize the variability of clade F HIV-1 strains isolated in Romania. PMID- 17281315 TI - Prediction and Analysis of Human microRNA Regulatory Modules. AB - MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. We propose a computational method to predict miRNA regulatory modules or groups of miRNAs and target genes that are believed to participate cooperatively in post-transcriptional gene regulation. We tested our method with the human genes and miRNAs, predicting 431 miRNA regulatory modules. The validations of predicted modules with the literature and Gene Ontology show that the genes in the modules appear to be closely related in specific biological processes, such as gene regulation involved in various cancers. PMID- 17281316 TI - Elimination of redundant protein identifications in high throughput proteomics. AB - Tandem mass spectrometry followed by data base search is the preferred method for protein identification in high throughput proteomics. However, standard analysis methods give rise to highly redundant lists of proteins with many proteins identified by the same sets of peptides. In essence, this is a list of all proteins that might be present in the sample. Here we present an algorithm that eliminates redundancy and determines the minimum number of proteins needed to explain the peptides observed. We demonstrate that application of the algorithm results in a significantly smaller set of proteins and greatly reduces the number of "shared" peptides. PMID- 17281317 TI - Mixture feature selection strategy applied in cancer classification from gene expression. AB - Recently, cancer classification based on gene expression has been developed. This gives a hope for the discrimination of cancer to a more systematic direction. However, there're many challenges existing in the new method. Maybe the most important one is the unbalance that so few training samples exist compared to so huge genes been collected. So feature selection becomes one center problem of the cancer classification. A novel mixture feature selection strategy has been proposed in this paper, it make use of the characters of filter and wrapper, and synthesis three feature selection methods: Pearson correlation analysis, Relief-F and SVM. PMID- 17281318 TI - Cross-study validation and combined analysis of microarray data for cancer using vector cosine angle method. AB - Cross-study validation and combined analysis of microarray data is critical in genomic analysis. With so much genetic expression data being produced by microarrays in the study of cancer, knowing the extent to which these studies agree can provide valuable insight. Researchers from Johns Hopkins University, Baltimore used Pearson correlation coefficient to develop a system for performing cross-study comparisons of gene expression profiles, found in three separate lung cancer studies, for validation and integration. This paper presents a vector cosine angle method to validate and analyze cross-study of microarray data for cancer and compare the robust of cross-study vector cosine angle validation with that of cross-study Pearson correlation validation. Results show it is effective and robust. PMID- 17281319 TI - Fractal Clustering and Knowledge-driven Validation Assessment for Gene Expression Profiling. AB - DNA microarray experiments generate a substantial amount of information about the global gene expression. Gene expression profiles can be represented as points in multi-dimensional space. It is essential to identify relevant groups of genes in biomedical research. Clustering is helpful in pattern recognition in gene expression profiles. A number of clustering techniques have been introduced. However, these traditional methods mainly utilize shape-based assumption or some distance metric to cluster the points in multi-dimension linear Euclidean space. Their results shows poor consistence with the functional annotation of genes in previous validation study. From a novel different perspective, we propose fractal clustering method to cluster genes using intrinsic (fractal) dimension from modern geometry. This method clusters points in such a way that points in the same clusters are more self-affine among themselves than to the points in other clusters. We assess this method using annotation-based validation assessment for gene clusters. It shows that this method is superior in identifying functional related gene groups than other traditional methods. PMID- 17281320 TI - Integration of clinical information and gene expression profiles for prediction of chemo-response for ovarian cancer. AB - Ovarian cancer is the fifth leading cause of cancer death among women in the United States and western Europe. Platinum drugs are the most active agents in epithelial ovarian cancer therapy. In order to improve the prediction of response to platinum-based chemotherapy for advanced-stage ovarian cancers, we describe an integrated model which combines clinical information tumor and treatment information, with gene expression profile. This integrated modeling framework is based on the support vector machine classifier that evaluates the contributions of both clinical and gene expression data. The results show that the integrated model combining clinical information and gene expression profiles improve the prediction accuracy compared to those made by using gene expression predictor alone. PMID- 17281321 TI - Improving Reliability of Response Prediction to Platinum-Based Therapy by AdaBoost and Multiple Classifiers. AB - It is a challenge to construct a reliable classifier based on microarray gene expression data for prediction of chemotherapy response, because usually only a small number of samples are available and each sample has thousands of gene expressions. This paper uses boosting and bootstrap approaches to improve the reliability of prediction. Specifically, AdaBoost and multiple classifiers based methods are used, in which support vector machines (SVMs) are utilized as the classifiers due to their good generalization ability. We compare the performance of proposed methods with a single SVM classifier system using MAS gene expression dataset in prediction of the response to platinum-based therapy for advanced stage ovarian cancers. Statistical tests show both of the proposed methods achieve better prediction performance and have good reliability in terms of mean and standard deviation of the prediction performance for different number of selected features. PMID- 17281322 TI - Tracking the herd: resynchronization analysis of cell-cycle gene expression data in Saccharomyces cerevisiae. AB - Identification of genes expressed in a cell-cycle-specific periodical manner is of great interest to understand cyclic systems which play a critical role in many biological processes. However, identification of cell-cycle regulated genes by microarray gene expression data is complicated by the factor of synchronization loss, thus remains a challenging problem. Decomposing the expression measurements will allow to better represent the single-cell behavior and improve the accuracy in identifying periodically expressed genes. In this paper, we propose a resynchronization-based algorithm for identifying cell-cycle-related genes, where we present a simple synchronization loss model by modeling the gene expression measurements as a superposition of different cell populations growing at different rates. The underlying expression profile is reconstructed through resynchronization and is further fitted to the measurements in order to identify periodically expressed genes. Results from both simulations and real microarray data show that the proposed scheme is promising for identifying cycling genes and revealing underlying gene expression profiles. PMID- 17281323 TI - Efficient gene expression analysis by linking multiple data mining algorithms. AB - The set of gene micro-arrays, which consists of two leukemia types, was used as a target to evaluate the efficiency of novel integrated data mining classification process. Discovering the most relevant subset of genes among few thousands of analyzed genes is necessary to get accurate disease classification. Dimensional complexity of the classification process was reduced by a filter based on mutual information feature selection coupled with the support vector machines classifier in the leave-one-out loop. The result was an efficient and reliable tool named MIFS/SVM hybrid. Optimal procedure parameters that enable accurate classification and attribute selection could be determined within an acceptable time frame. PMID- 17281324 TI - Gene networks inference from expression data using a recurrent neuro-fuzzy approach. AB - The reverse engineering paradigm is given increasing attention in computational molecular biology lately. One of the goals is to understand how gene regulatory networks (complex systems of genes, proteins and other molecules) function and interact to carry out specific cell functions. We present an approach for inferring the complex causal relationships among genes from microarray experimental data based on a recurrent neuro-fuzzy method. The method derives information on the gene interactions in a highly interpretable form (fuzzy rules) and takes into account dynamical aspects of genes regulation through its recurrent structure. We tested our approach on a set of genes known to be highly regulated during the yeast cell-cycle. The retrieved gene interactions correspond to the ones validated by previous biological studies, while our method surpasses previous computational techniques that attempted gene networks reconstruction, being able to retrieve significantly more biologically valid relationships among genes. At the same time, our method is able to predict time series for the expression of the genes based on the information extracted from a training subset of the data. The results prove highly accurate prediction capability. PMID- 17281325 TI - Improvement of SVM Algorithm for Microarray Analysis Using Intelligent Parameter Selection. AB - Identification of genetic markers is a crucial step in the diagnosis, prognosis, and treatment of disease. This paper focuses on the application of a supervised classification technique, support vector machines (SVM), to high dimensional microarrays for marker identification. A case study of renal cell carcinoma (RCC) is used here to demonstrate and test the ability of SVMs to identify real biological markers. SVMs are known to be suitable for high dimensional microarray data and are able to classify non-linear relationships in the data through the use of kernel functions specific to the datasets. This paper compares multiple SVM kernel functions, both linear and nonlinear, to determine which form is best suited for a particular dataset. Additionally, each SVM is tested across a range of parameters and normalization schemes to further identify a specific optimal classifier. Empirical results are then used to determine the optimum parameters for the SVM to efficiently find biologically important predictive markers for differentiation between RCC subtypes for the purpose of diagnosis and prognosis. PMID- 17281326 TI - Study on a nanoparticle system for buccal delivery of insulin. AB - In this paper, a nanoparticle system of insulin (NSI) was prepared for buccal transmucosal delivery of insulin. The average size of the suspending particles was 67.5 nm, and a possible microstructure of the nanoparticles in the system was proposed. The transmucosal ability of insulin was evaluated in rabbits from the views of the hypoglycaemic rate and pharmacokinetics. The average bioavailability of NSI by buccal delivery versus subcutaneous injection is 18.3%. These results indicate that the studied nanoparticle system may be promising vehicles for the buccal delivery of insulin. PMID- 17281327 TI - Modulation of nano-selenium on tetrodotoxin-sensitive voltage-gated sodium currents in rat dorsal root ganglion neurons. AB - Nano-Selenium, a novel Nano technology production, was demonstrated to be useful in medical and scientific researches. Here, we investigated the effects of Nano Selenium on tetrodotoxin-sensitive (TTX-S) voltage-dependent Na+channels in isolated rat dorsal root ganglion neurons, using whole cell patch-clamp method. Nano-Selenium irreversibly decreased TTX-S Na+current (INa) in a concentration-dependent manner and shifted the maximum of the current/voltage relationship from -67mV to -52mV, without modifying the threshold potential of the current. Nano-Selenium shifted the steady-state activation and inactivation curves to the left. In the contrast of Na2SeO3, the inhibition effect of 1nM Nano-Se was much stronger. The cell treated with 1nM Na2SeO3firstly, still respond to futher addition of 1nM Nano-Selenium. These results prove Nano Selenium to be a novel antiagonist, acted within the channel pore, not on or near the exterior surface of the channel protein where it would experience the membrane electric field, which possesses a distinct binding site from Na2SeO3. PMID- 17281328 TI - Potential Applications of Untethered Microdevices in the Blood Vessels within the Constraints of an MRI System. AB - This paper presents potential medical applications that an untethered microdevice in the cardiovascular system could perform within an MRI system. Recent developments and continuing evolution in micro/nano fabrication and design techniques will enable the development of functional microdevices able to explore the cardiovascular system. The Magnetic Resonance Submarine (MR-Sub) project is a first step towards this goal. Magnetic force generated by the gradient coils of an MRI system provides a propulsion mechanism that simplifies miniaturization and bypasses energetic challenges. Untethered microdevices may play an important complementary role in the next generation of minimally invasive tools. A better efficiency and targetability of the treatments will be achieved when microsystems such as the MR-Sub will allow a more extensive access to smaller blood vessels. PMID- 17281329 TI - Viscoelastic properties of human mesenchymal stem cells. AB - In this study, we investigated the viscoelasticity of individual bone marrow derived adult human mesenchymal stem cells (hMSCs), and the role of specific cytoskeletal component-F-actin microfilaments on the mechanical properties of individual hMSCs. The mechanical properties of hMSCs were determined using the micropipette aspiration technique coupled with a viscoelastic solid model of the cell. For the hMSCs under control conditions the instantaneous Young's modulus E0 was found to be 886plusmn289(Pa), the equilibrium Young's modulus Einfin 372plusmn125(Pa), and the apparent viscosity mu 2714plusmn1626(Pamiddots). After exposed to 2muM of chemical agent-cytochalasin D that disrupt the F-actin microfilaments, the Young's moduli of hMSCs decreased by up to 72% and the apparent viscosity increased by 167%. These findings suggest that microfilaments are crucial in providing the viscoelastic properties of the hMSCs, and changes in the structure and properties of them may influence the mechanical properties of hMSCs significantly. PMID- 17281330 TI - Micro-thermocouple probe for measurement of cellular thermal responses. AB - We have produced micro-thermocouple probes for the measurement of cellular thermal responses. Cells generate heat with their metabolisms and more heat with reactions to a certain physical or chemical stimulation. Therefore, the analysis of the cellular thermal responses would provide new physiological information. However, a real-time thermal measurement technique on a target of a single cell has not been established. In this study, glass micropipettes, which are widely used in bioengineering and medicine, are used for the base of the thermocouple probes. Using microfabrication techniques, the junction of two different metal films is formed at the micropipette tip with a diameter of 1 μm. This probe can inject a chemical substance into a cell and to detect its subsequent temperature changes simultaneously. PMID- 17281331 TI - The Study on Bionic Olfactory Neurochip Based on Light-addressable Potentiometric Sensor. AB - Olfactory system can distinguish thousands of odors. In order to utilize biological olfactory neurons as sensitive material of electronic nose, this article reports an olfactory neurochip as real bionic technique for odorants detection. Effective cultures of olfactory receptor neurons and olfactory bulb cells on the chip have been achieved. Using light-addressable potentiometric sensor (LAPS) as sensing chip to monitor extracellular potential of the neurons, we tested the response under stimulations of the odorants or neurotransmitters, such as acetic acid and glutamic acid. The results demonstrate that this kind of the LAPS and olfactory neurons hybrid system is sensitive to environmental changes, which has potential to be used as a novel bioelectrical nose for detecting odors. PMID- 17281332 TI - Dielectrophoresis and theoretical studies of dipolar chaining effects in cells. AB - The development of microelectrode-based technologies has facilitated the development of sophisticated methods for manipulating and separating cells, bacteria, and other bioparticles. For many of these various applications, the theoretical modeling of the electrical response of compartmentalized particles to an external electric field is important. This paper describes a new boundary element method, derived from a consideration of the charge densities induced at the interfaces of a compartmentalized particle, for modeling the dielectric properties of cells. Experimental validation of this theoretical model has been obtained by investigating the influence that dipolar ;pearl-chaining' effects have on the dielectrophoretic behavior of human T lymphocytes. PMID- 17281333 TI - Study of the Effects of 50Hz Homogeneous Magnetic Field on Expression of Bax, Bcl 2 and Caspase-3 of SNU Cells In Vitro. AB - We investigate the effects of magnetic field on expression of Bax, Bcl-2 and Caspase-3 of SNU (human low differentiated gastric adenocarcinoma cell line) in this article. SNU cells were randomly divided into control groups and four treatment groups, the treatment groups were respectively irradiated by 50Hz homogeneous ferromagnetic field (0.097T) 5min, 30min, 60min and 120min. SNU cells were harvested for detection of Bax, Bcl-2 and Caspase-3 antigen with flow cytometric analysis (FCM), immunocytochemical staining and Western blot. The expression of Bax and Caspase-3 in all magnetic field exposure groups were higher than that in control by FCM, immunocytochemical stain and Western blot, but the expression of Bcl-2 in all magnetic field exposure groups were lower than that in control by FCM, immunocytochemical stain and Western blot. We concluded that possible mechanisms of apoptosis of SNU cells after 50Hz homogeneous ferromagnetic field (0.097T) treatment may be Up-regulating the expression of Bax and Caspase-3, dowm-regulating the expression of Bcl-2. PMID- 17281334 TI - Effects of 50Hz Homogeneous Ferromagnetic Field on the Concentrations of Intracellular Calcium-ion of SNU Cells and Lymphma Cells In Vitro. AB - The study was designed to observe the effects of 50 Hz homogeneous ferromagnetic field (0.097T) exposure on change of intracellular Calcium-ion concentration of human low differentiation gastric adenocarcinoma cell line - SNU and lymphocytes in vitro. SNU cells and human peripheral blood lymphocytes in vitro were exposured to 50 Hz homogeneous ferromagnetic field at different time periods. Cells were harvested after magnetic field exposure. The concentration of intracellular Calcium-ion of cells in control and different experimental groups were measured with confocal microscope. The concentration of intracellular Calcium-ion of SNU cells and human peripheral blood lymphocytes were all increased after magnetic field exposure. 50Hz homogeneous ferromagnetic field exposure could induce increases of the concentration of intracellular Calcium-ion of SNU cells and human peripheral blood lymphocytes in vitro. PMID- 17281335 TI - Evaluation of Alginate coated Chitosan Membrane for Guided Tissue Regeneration. AB - Chitosan membranes prepared by a thermal induced phase separation method and then alginate was coated onto the membrane on one side by a modified dialysis apparatus to prepare alginate/chitosan membranes (A/C membranes). ESCA analysis, SEM observation and contact angle measurements were conducted to evaluate the differences existed in the surface properties. Besides, mechanical strength, degradation behavior and especially, cell adhesion test was also examined to survey the feasibility of using this type of A/C membrane in guided tissue regeneration (GTR) application. The preliminary results obtained revealed that alginate could effectively be coated onto the chitosan membrane (from ESCA and SEM results). The contact angle decreased on the alginate side as compared with the chitosan-side (from 88.4deg to 34.2deg). The A/C membrane had a water higher content of 71.8 % as compare with the chitosan membrane (61.8%). Chitosan membranes coated with alginate also increased the Young's modulus and the ultimate strength, whereas, the elongation of these membranes were remained at the same range. A/C membrane and chitosan membrane prepared in this study degraded to about 75% of initial weight after a 30-day in vitro shaking test. The 3T3 fibroblast cells showed less adhesive on alginate side as compared with the chitosan side and glass surface in cell adhesion test. The obtained results from this study suggested that the alginate molecules could be coated onto the chitosan membrane by our modified dialysis apparatus and provided a different surface morphological structures and properties of chitosan membrane. This A/C membrane could provide extra benefits and potentials than chitosan membrane used in GTR applications. PMID- 17281336 TI - Application of nanoindenter in investigating properties of the cuticle of dung beetle. AB - The cuticle of insects is multilayered structure at positioning. A Berkovich tip was used for the tests. micro- or nano-scale in vertical direction. This work investigated the mechanical properties of the cuticle of dung beetle Copris ochus Motschulsky using nanoindenter. It was shown that the nanomechanical properties of the cuticle were different for each layer of the cuticle and its normal nanoindentation was resulted from the composite effect of the all layers. PMID- 17281337 TI - A novel porous natural polymer scaffold for tissue engineering. AB - A novel porous polymer scaffold fabricated by salt-leaching method for tissue engineering was developed and the mechanical properties and porosity were investigated in our study. Scanning electronic microscopy (SEM) was employed to observe the morphology and structure of porous scaffolds. Cytocompatility of the porous scaffolds were evaluated, using HL-7702 cells as model, in terms of cell attachment and cell viabilities from 3 to 72 hours determined by MTT method. RESULT: These scaffolds possessed a total porosity of 64.2%, compressive Young's modulus of (31.8±6.5) MPa. The particle size of porogen has little effect on the compressive properties and porosities. In addition, the morphology of pores observed by SEM showed good pore interconnectivity within the porous scaffolds. HL-7702 cell viabilities kept at high level during the whole incubation period. PMID- 17281338 TI - Natural hydroxyapatite/chitosan composite for bone substitute materials. AB - We developed the natural hydroxyapatite/chitosan composite that could be molded into any desired shape. The powder component consists of natural hydroxyapatite, which is epurated from bone of pigs. The liquid component consists of malic acid and chitosan. To study the possibility of the composite on repairing bone defects, 15 white rabbits were each operated on left tibias to create two square bone defects. One of the defects was reconstructed with the composite; the other was not repaired as a blank control. 3 of the animals were killed at the end of 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks respectively to be evaluated with anatomy and histology. No apparent reject reaction was found, except for a mild inflammatory infiltrate found at postoperative 2 weeks. Fibrous tissue became thinner at postoperative 2-8weeks and bony connection was partly shown at postoperative 12 weeks. The new bone was the same as the recipient bone at postoperative 16 weeks. The hydroxyapatite/chitosan composite has good biocompatibility and osteoconduction. It is a potential repairing material for clinical application. PMID- 17281339 TI - Quantitative Evaluation and Secondary Structure Analysis of Proteins Adsorbed on Biomaterial Surfaces Using FTIR. AB - The quantity and secondary structure of adsorbed albumin (Alb) and immunoglobulin G (IgG) on two kinds of biomaterial surfaces-polyurethane (PU (H50-50)) and polystyrene (PS) were studied using Fourier transform infrared spectroscopy (FTIR). The original spectra tested by FTIR were processed using second derivation and self-deconvolution techniques to obtain the content of different secondary structures of adsorbed proteins, which could be used to evaluate the denatured degree of proteins. Results showed that the quantity of Alb adsorbed on PU (H50-50) surface is larger than PS. The hydrophobic features of material played a role in conformational change of adsorbed protein, and indicated that the denatured degree caused by hydrophobic PS was greater than hydrophilic PU (H50-50). The blood compatibility of PU (H50-50) was likely to be better than PS. PMID- 17281340 TI - Effects of freezing on the cytoskeleton, focal adhesions and gap-junctionsin murine osteoblast cultures. AB - Understanding the ultra-structural response of cells to the cryopreservation process is important for designing cryopreservation strategies for cells and tissues. Cell-cell interaction and cell-scaffold interactions alter cryopreservation response and, in turn, the cellular structures involved in adhesion and intercellular contact are targets of cryopreservation-induced damage. Immuno-fluorescence was used to assess the status of the actin filaments, vinculin (focal adhesion) and connexin-43 (gap junction) of murine osteoblasts attached to hydroxyapatite (HA) discs glass coverslips for a two-step freezing process. The freezing process de-polymerized and distorted the F-actin of dead cells, while that of live cells has little change. Vinculin and connexin-43 structures were rarely seen in dead cells, a portion of vinculin and connexin-43 remained in live cells. These results suggest that focal adhesions and gap junctions may support the cells robustness during cryopreservation. The present study helps investigate the damage mechanism of attached cells during freezing process. PMID- 17281341 TI - Factors Influencing the Formation of MSCs APA Microcapsules. AB - This paper aims to produce alginate-(poly-l-lysine)- alginate(APA) microcapsules of MSCs(mesenchymal stem cell), and to investigate the influencing factors of cell microcapsules' formation. Bone marrow mesenchymal stem cells were enclosed within APA microcapsules by a high-voltage electrostatic microcapsules generator. The factors influencing the uniformity, integrity and the ratio of successful microcapsules were investigated. It showed that the cell density, the concentration of alginate solution and the purity of cell solution have a significant effect on the formation of microcapsules. When the cell density is 3×106/ml, alginate concentration is 1.75%, centrifugal times is twice, perfect microcapsules with good sphericity, uniformity, and the diameter at 200 to 300μm could be made. PMID- 17281342 TI - Lethal Effects of Steep Pulsed Electric Field (SPEF) to Target Lymphatic Capillaries in VX2Implanted Breast Cancer of Rabbits. AB - This paper discussed the lethal effects of Steep Pulsed Electric Field (SPEF) to target lymphatic capillaries in VX2implanted breast cancer of rabbits using methylene blue dye injection staining, 5'-AMP-ALPase enzyme histochemical double staining, electron microscopy and VEGF-C observations. The result of methylene blue dye perfusion showed that the edge of tumor treated with SPEF was indistinct, no circularity or liner structure. Enzyme histochemical staining examination displayed that no positive staining was found in SPEF-target region of breast tumor, and lymphatic capillaries presented piecemeal structure in the edge of target region. Transmission electron microscopic examination showed that the continuity and integrality of lymphatic capillaries in tumor were destroyed after the treatment of SPEF. The expression of VEGF-C decreased markedly. The experiment indicated that SPEF induced the severe destruction of tumor cell and lymphatic capillaries in target region, and inhibited proliferation of lymphatic. Therefore it can decrease the possibility of lymphatic metastasis. PMID- 17281343 TI - Three-Dimensional Culture of Human Periodontal Ligament Cells on Highly Porous Polyglycolic Acid Scaffolds in vitro. AB - Periodontal tissue engineering represents a possible approach to regenerate the human periodontal ligament (PDL) around dental implants. The aim of this study was to observe the morphological and biological property of the human periodontal ligament cells that were three-dimensional (3D) cultured onto PGA scaffolds in vitro. The human periodontal ligament cells were seeded and cultured onto PGA 3D scaffolds, and then the cellular morphology and structure, adhesion and biocompatibility with scaffolds were evaluated by light microscope and scanning electronic microscope, and the cellular type I collagen synthesis was observed by method of immunohistochemical staining with anti-type I collagen antibody. The results indicated that the human periodontal ligament cells adhere to scaffolds well and exhibit the excellent matrix secretion ability under light microscope and scanning electronic microscope, type I collagen was expressed positively in cell-scaffolds complex by immunohistochemical staining. These results suggested that delivery of PDL Cells via non-woven PGA mesh may serve as a viable approach for promoting periodontal tissue regeneration and provides a possibility of PDL regeneration on dental implants. PMID- 17281344 TI - Collagen-based Tissue Engineering as Applied to Heart Valves. AB - Using the method of directed collagen gel shrinkage, we have been fabricating heart valves and mitral valve chordae [1,2,3]. The principle involves mixing solubilized collagen with the appropriate cells. When the collagen-cell mixture is neutralized, soluble collagen reassembles into fibrils and a gel is created. When the gel is mechanically constrained, the collagen fibrils align in the direction of constraint. The generation of tensile force during contraction is crucial for the formation of highly aligned, compacted collagenous constructs. So far, inappropriate mechanical properties have been one of the main limitations of most collagen-based tissue equivalents. In this study, we focused on providing both biomechanical and biochemical stimuli to increase cellular proliferation, matrix synthesis, and hence improve the mechanical properties of the collagen constructs. We explored a number of holder materials and configurations, with an objective to maximize the lateral compaction of our constructs. We designed a bioreactor that can provide controlled static tension to our collagen constructs. We also developed a nutrition-fortified medium that includes trace elements (Zn2+, Cu2+, Fe2+ and Mn2+), various amino acids, and vitamins (A, B complex, and C). Our ultimate goal was to combine biomechanical and biochemical stimuli, and enhance the mechanical strength of our collagen constructs. PMID- 17281345 TI - Transdifferentiating potential of the human peripheral blood mononuclear cell transplanted into myocardial infarction model of nude mouse. PMID- 17281346 TI - A Potential Excitability Was Induced by Basic Fibroblast Growth Factor during Early Differentiation of Neurons from Mouse Embryonic Stem Cells in vitro. AB - We report that basic fibroblast growth factor (bFGF) induces the release of glutamate in ES-derived neurons during early stages of differentiation. Changes of Ca2+concentration labeled by fluorescence intensity occurred in response to minimal concentrations of glutamate. The Ca2+concentration was changed more rapidly by bFGF than by glutamate during the early stages of differentiation of ES-derived neurons. High concentrations of the inhibitor MK801, a N-methyl-D-aspartate (NMDA) receptor antagonist applied before bFGF stimulation caused a dramatic decrease of fluorescence intensity in neurons derived from both hippocampal and ES cells. These results showed that bFGF induces glutamate release and an increase of [Ca2+] in neurons during early stages of differentiation, and that the increase of [Ca2+] can be inhibited by MK801. Therefore, we concluded that bFGF serves not only as a neurotrophin but also as a stimulator of excitability during the differentiation of ES cells into neurons. PMID- 17281347 TI - Preliminary results related to the principle and application of drug galvano acupuncture. AB - Drug galvano-acupuncture is a new medical therapy that has been developed and refined over thirty-one years of research and clinical practice. It uses a combination of modern technology, traditional acupuncture, herbal medicine, and massage therapy techniques. The therapy works by inducing an electric field at the surface of the skin that allows various medications to penetrate the skin's surface. The interacting combination of medication, along with electrical and mechanical stimulation, appears to quickly produce healing effects with no side effects. This method has been broadly used with what appear to be positive effects on a number of different conditions, including neuralgia, asthma, and stroke. PMID- 17281348 TI - The study of whole-body chemohyperthermic tumour treatment by extracorporeal circulation. AB - Chemohyperthermic tumor treatment has developed quite rapidly over the past 20 years, and its therapeutic effect is widely known from clinical practice. More recently it has been realized that whole-body chemohyperthermic tumor treatment by extracorporeal circulation is quite a unique approach with which the patient's blood is withdrawn from femoral artery through a peristaltic pump to a heat exchanger and then back to the patient's femoral vein. Tumor cells can be effectively killed when the temperature of the blood is controlled at about 42°. It has been proven that the extracorporeal chemohyperthermia is an effective alternative in malignant tumor treatment, especially for those who have missed the best therapeutic opportunities or whose cancer cells have recurred or propagated. PMID- 17281349 TI - The role of opioid in the mechanism of the hypotensive effect by simulating acupuncture on rat hindlimb. AB - The present study investigated the role of central opioid in the hypotensive effect of somatic afferent inputs. The femoral arterial pressure and electrocardiogram (ECG) of rats were recorded when the hypothalamic paraventricular nucleus (the PVN) was electrically stimulated or chemically activated (microinjection of L-glutamate) with or without microinjection of naloxone into the lateral ventricle of brain. Stimulation of the deep peroneal nerve (the DPN) decreased the pressor response elicited by electrical stimulation or chemical activation of the PVN. This inhibitory effect was reduced by microinjection of naloxone into the lateral ventricle of brain. These data suggest that opioid receptor in brain is involved in the inhibitory effect of stimulating the DPN on the pressor response induced by activation of the PVN. PMID- 17281350 TI - Cutaneous Electrical Stimulation of Mid-frequency on Acupiont Affects the Electrogastrogram. AB - Acupuncture, including the manual acupuncture, electroacupuncture and cutaneous electrical stimulation on acupiont, is known to enhance the gastric motility. The aim of this paper is to study the changes in electrogastrogram (EGG) when the acupiont Zusanli is stimulated cutaneously by electrical signal of mid-frequency. The result shows that the regularity of EGG is enhanced after the stimulation, and the improvement is more obvious in the EGG recorded near the antrum. PMID- 17281351 TI - The quantization of chinese deep pulse. AB - Clinic Chinese pulse diagnosis is done by using fingers to touch the radial artery on the wrist to get the floating, middle, and deep pulses. However, the pressure of deep pulse is not an absolute value. It depends on many individual factors, such as age, height, weight, sex, and flexibility of blood vessel. It is very difficult to make a correct judgment without sufficient experience. Each Chinese doctor always has different results from measuring blood pulses of radial artery. So how to make a quantitative method for Chinese pulse diagnosis is very important. In this paper, we propose a scheme using modified blood pressure monitor and oscillometric method to quantize and standardize the deep pulse. Our scheme provides a method which is independent of personal factors and could get better accuracy when compared with other methods for Chinese pulse diagnosis. PMID- 17281352 TI - An Acupuncture-like Quantitative Mechanical Stimulator. AB - A stimulator that analogs the needle puncture has been designed to deliver quantitative mechanical stimulus to a small area of muscle. A friction coupler is designed to transmit the driving force from motor to a needle which is used to deliver stimulus. Rotation of the needle may be stopped but the friction will be maintained between the needle and the tissue when this friction moment comes to the driving moment of the coupler. Experiments were done on 6 hindlimb muscles in 2 cats and the results show the value of the stimulator in probing the mechanisms of acupuncture. PMID- 17281353 TI - EAV and Gemmotherapy - Medicine for the Next Millennium? (technique as a means to link eastern and western medicine). AB - These article give you basic information about technique as a means to link eastern and western medicine based on using combination of EAV (Electro Acupuncture According to Dr. Voll) and gemmotherapy, a special form of phytotherapy. Experience with this method continues to grow steadily and some very interesting results are already available today. Based on the results of treatment achieved in our practice so far (17.000 examinations during 10 years), we are convinced that EAV and gemmotherapy will become, and in fact has already become, a successful natural treatment method for the 21st century. PMID- 17281354 TI - Correlating heart rate variability with skin impedance measurements. AB - To determine the interaction between skin impedance, measured at acupuncture points, and autonomic nervous response, as expressed through heart rate variability (HRV), we propose a method for correlating frequency components of non-uniformly sampled R-R intervals and the impedance measurements. Since vagal response typically manifests itself in the High Frequency (HF) range of HRV, Lomb Welch periodograms (LWp) are used to evaluate accurately the HF band spectral components. The resampling rate of the LWp is adjusted according to the window/filter used to meet a -20dB antialiasing requirement. The record length of each individual LWp is then chosen such that the frequency component resampling rate matches the impedance sampling rate. Since it is not feasible to use the phase information, the magnitudes of the frequency component samples are used in the evaluation of the cross-covariances between the HRV components and the impedance signals. PMID- 17281355 TI - Thermodynamics model and experimental validating on thermal field distribution of traditional moxibustion. PMID- 17281356 TI - Tongue area extraction in tongue diagnosis of traditional chinese medicine. AB - The extraction of tongue area from digital photos is essential to an automatic tongue diagnostic system in traditional Chinese medicine. Simple segmentation methods couldn't be effective due to the weak edge of tongue and the details on the tongue's surface. In this paper, we propose a unique segmentation method based on the combination of the watershed transform and active contour model (ACM). The watershed transform is used to get the initial contour, and an active contour model, or "snakes", is used to converge to the precise edge. This method is proved to be effective and steady in experiments on tongue image. PMID- 17281357 TI - Application of cell engineering of herbal Medicine treating bone resorption of osteoclasts. AB - To investigate application of cell engineering in herbal Medicine treating bone resorption. STUDY DESIGN: the bone marrow cells were isolated from 5 week-old SD rats and induced by 1,25(OH)2D3. Firstly, Morphological assay, cells were fixed, stained by tartrate-resistant acid phosphatase (TRAP) and observed with the fluorescence micrograph. F-actin rings of OCLs were labled using Bodipy FL Phallacidin and PI, and observed with the laser scanning confocal microscope, then also showed the ultrastructure of them with the scanning electron microscope. Secondly, bone pits were observed after bone slices were stained by paraosaniline hydrochloride. Thirdly, the number of TRAP (+) cells with above two nuclei was counted, and TRAP activity of OCLs was examined with TRAP kit. In addition, effects of Traditional Chinese Medicine, such as Oral Liquid of Guiluerxian, on the differentiation and function of OCLs were observed. Results indicated that application of cell engineering made it possible to observe vividly the morphology of osteoclasts, study its function and mechanism underlying bone resorption. PMID- 17281358 TI - Loureirin B: An Effective Component in Dragon's Blood Modulating Sodium Currents in TG Neurons. AB - To test, analyze and express the relationship between the pharmacological effect of Traditional Chinese Medicine (TCM) dragon's blood and that of its component loureirin B, specify an operational definition for effective component from raw drug of TCM. Using the whole-cell patch-clamp technique, the effects of dragon's blood and its component loureirin B on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents in trigeminal ganglion (TG) neurons were observed. The results show that both dragon's blood and loureirin B suppressed two types of peak sodium currents in a dose-dependent way. 0.1% dragon's blood and 0.2mmol/L loureirin B affected the activation and inactivation of sodium channels. The results further prove the analgetic mechanism of dragon's blood interfering with the nociceptive transmission. According to the above definition, loureirin B is the effective component in dragon's blood modulating sodium currents in TG neurons. PMID- 17281359 TI - Research progress of triptolide-loaded nanoparticles delivery systems. AB - Triptolide is one of the major active components of traditional Chinese Medicine (TCM) - Tripterygium wilfordii Hook. f. (TWHf), which has been reported to be effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, especially rheumatoid arthritis. However, its clinical use is restricted due to its scarce water solubility and some toxic effects. In order to find innovative ways for administering triptolide and alleviating its disadvantages, the novel types of delivery systems have been developed. This paper reviews the studies of triptolide- loaded nano drug delivery systems (NDDS) in our group during the past three years. The preparation, characterization, pharmacology and toxicity of triptolide-loaded solid lipid nanoparticles, microemulsions and polymeric nanoparticles were investigated. The results indicated that the NDDS presented more powerful activity and a lower toxicity in comparison with common drug carrier. PMID- 17281360 TI - Fuzzy Logic-based Recognition of Gait Changes due to Trip-related Falls. AB - The main aim of this paper is to explore application of fuzzy rules for automated recognition of gait changes due to falling behaviour. Minimum foot clearance (MFC) during continuous walking on a treadmill was recorded on 10 healthy elderly and 10 elderly with reported balance problem and tripping falls. MFC histogram characteristic features were used as inputs to the set of fuzzy rules; the features were extracted based on estimating the clusters in the data. Each of the clusters found corresponded to a new fuzzy rule, which were then applied to associate the input space to an output region. Gradient descent method was used to optimise the rule parameters. Both cross-validation and Jack-knife (leave-one out) techniques were utilized for training the models and subsequently, testing the performance of the optimized fuzzy model. Receiver operating characteristics (ROC) plots, as well as accuracy rates were used to evaluate the performance of the developed model. Test results indicated up to a maximum of 95% accuracy in discriminating the healthy and balance-impaired gait patterns. These results suggest good potentials for fuzzy logic to use as gait diagnostics. PMID- 17281361 TI - Musculotendon parameters estimation by ultrasound measurement and geometric modeling: application on brachialis muscle. AB - Computational modeling for musculoskeletal system provides quantitative insights in analyzing human movement. One of the major challenges in neuromusculoskeletal modeling is to accurately estimate the musculotendon parameters on subject specific basis. The ultrasound imaging technology presents a new approach to obtain the parameters in vivo. The pennation angle and fascicle length of brachialis (BRA) were measured in vivo with the use of ultrasonography to investigate the relationship between these muscle architecture parameters and elbow joint position. A generic interactive graphics-based geometrical model of the upper limb and BRA was developed to get the musculotendon length and moment arm of the muscle. The results indicate human brachialis architecture is significantly affected by changing of joint angle at passive horizontal movement. These in-vivo measurements provide subjects-specific information and these muscle parameters can be used to set up the neuromusculoskeletal model for the muscle force and torque estimation. PMID- 17281362 TI - Finite element modeling and biomechanical analysis of eyeball and extraocular muscles. AB - Finite Element Analysis (FEA) plays an important role in the biomechanical field. In this paper, we used FEA method in the area of ophthalmology. We generated an eyeball - extraocular muscles (EOMs) model and converted it to meet the need of FEA process. We exerted outside forces on the structure for nonlinear computation and achieved the distributions of displacement, stress and strain. The results corresponded with the basic theory of ophthalmology. We also put forward some related aspects for discussion and advanced studies. PMID- 17281363 TI - Towards an Integrated System for Estimating Multi-joint Movement from Diverse Sensor Data. AB - Motion capture has been an active research field for many years. Previous methods have mostly focused on converting segment orientations into joint angles. However such methods have a number of drawbacks: the estimates of joint angles are not optimal in a statistical sense; the common assumption that sensor placement is known and constant (relative to the limb) is in practice violated; existing methods are tailored to specific types of motion capture hardware, and cannot be easily adapted to new equipment or to situations where multiple sensor types are used simultaneously. This paper presents an approach that aims to resolve these problems, by combining modern statistical inference with domain-specific optimization. Our algorithm allows arbitrary collections of sensors to be used simultaneously (e.g. position and orientation markers, goniometers, gyroscopes), infers the sensor placements and segment sizes along with the time-varying joint angles (allowing the user to attach sensors quickly and inaccurately), and provides error bars for all quantities that it estimates. PMID- 17281364 TI - Stability analysis of nonlinear muscle dynamics using contraction theory. AB - Biological motor control systems have a distributed, rather than centralized, architecture. Instabilities in movement, such as tremor, can in part arise from the interactions between different physiological feedback mechanisms. Contraction theory provides tools for analyzing the stability of nonlinear distributed control systems. Here we use contraction theory to investigate the stability provided by the mechanical feedback of muscle dynamics, finding that these dynamics are exponentially stable. This theoretical result complements previous computational and experimental findings regarding the efficacy of viscoelastic properties of muscle in compensating for disturbances. PMID- 17281365 TI - Non-negative matrix factorization algorithms modeling noise distributions within the exponential family. AB - We developed non-negative factorization algorithms based on statistical distributions which are members of the exponential family, and using multiplicative update rules. We compared in detail the performance of algorithms derived using two particular exponential family distributions, assuming either constant variance noise (Gaussian) or signal dependent noise (gamma). These algorithms were compared on both simulated data sets and on muscle activation patterns collected from behaving animals. We found that on muscle activation patterns, which are expected to be corrupted by signal dependent noise, the factorizations identified by the algorithm assuming gamma distributed data were more robust than those identified by the algorithm assuming Gaussian distributed data. PMID- 17281366 TI - Relationships between Sensory Stimuli and Autonomic Regulation During Real and Virtual Exercises. AB - For expanding application of virtual reality, such as rehabilitation engineering, concerns of cybersicknes should be cleared. We have investigated changes in autonomic regulations under real cycling and virtual mountain biking video with the first-person viewpoint. The results showed that the dominant sensory stimuli affected autonomic regulation with different process. The different process will lead to the hints for preventing cybersickness. PMID- 17281367 TI - Optimization of goal-oriented voluntary movements. AB - A four-segment biomechanical model and a control characterizing the action of the central nervous system (CNS) are used to investigate optimization of the postural stabilization process and the execution of voluntary movement. The point-to-point voluntary movement is optimized using different measures of performance (cost functions) in the time- and frequency domains. In particular kinematic measure (jerk) and an LQ-type measure are considered and compared. The results of the study show that jerk optimization is better suited for musculoskeletal systems in synthesis of voluntary movement. These results are consistent with the existing literature. PMID- 17281368 TI - Change of paraspinal muscle spindle resting discharge evoked by mechanical vibration. AB - Mechanical vibration is experienced by people in some occupations. Low back pain has been linked to whole body vibration. The resting discharge of 26 paraspinal muscle spindles of anesthetized cats were recorded at L6 dorsal roots before, during and after the application of mechanical vibration at L6 spinous process. Paired student's t-test was used to compare the resting discharge before and after mechanical vibration. After vibration, the mean instantaneous frequency of the resting discharge for most of the muscle spindles (81%) decreased significantly (P<0.01). The average normalized decrease was -9.4%. The coefficient of variation for instantaneous frequency for most muscle spindles (62%) increased significantly (P<0.01). The average normalized increase was 60.5%. The results shed light on changes in proprioceptive input from the low back that can be induced by mechanical vibration. PMID- 17281369 TI - Sensory Motor Responses in Virtual Environments: Studying the Effects of Image Latencies for Target-directed Hand Movement. AB - Image latencies occur when a virtual environment (VE) responds to hand movements of its operator. A study has been conducted to investigate the effects of, and interactions among, hand movement related image latencies, target distance, and target width on discrete manual control tasks in a VE. In the presence of latencies, completion times of hand movement tasks have been found to obey Fitts' law. Significant interactions were found between the effect of latency and target width, but not between the effect of latency and target distance. Results suggest that, in the presence of hand movement-related image latencies, the effects of target width and target distance should not be analyzed as a combined single effect of ;Index-of-Difficulty'. PMID- 17281370 TI - The application of wavelet transform and neural network to surface electromyographic signals for pattern recognition. AB - The surface electromyographic (SEMG) signal, which is produced by neural and muscular systems, is a complicated bioelectric signal recorded from skin surface using electrodes. It is very helpful for doctors to analysis the illness of patients. In the paper, four channel SEMG signals from four muscles (palmaris longus, brachioradialis, flexor carpi ulnaris, biceps brachii) are analyzed with wavelet transform, and the eigenvalues of 6 layers wavelet decomposition coefficients are distilled, and eigenvector is composed to input the Elman neural network classifier to identify different movement patterns. The eight movement patterns (to make a fist, to spread a fist, wrist circumrotates entad, wrist circumrotates forth, to bend wrist, to spread wrist, forearm circumrotates entad, forearm circumrotates forth) can be successfully identified after training. It is a new method for SEMG signal study and experiments show that it facilitates higher identification rate. PMID- 17281371 TI - Application of independent component analysis and expansion matching filter for automatic detection of motor unit action potential trains. AB - The purpose of this study is to strengthen feature of MU discharge for classification of motor unit action potentials (MUAPs) into each MUAP train by means of the combination between expansion matching filter and independent component analysis (ICA). From our results, it is found that, when a MUAP waveform is used as a template, expansion coefficients give higher responses at the time points when similarity between the template and candidate MUAP waveforms is higher by applying expansion matching filter to multi-channel sEMG signals. Furthermore, because it is expected that the distribution of an expansion coefficient sequence including the MUAP train similar with the template have higher kurtosis value, only a component including a small number of MUAP trains can be extracted by additional application of ICA to expansion coefficients. Therefore, the fact suggests that this method assist to simplify and decompose classification of MUAPs only with a computer without heuristic operations. PMID- 17281372 TI - Development of a CPM Machine for Injured Fingers. AB - Human fingers are easy to be injured. A CPM machine is a mechanism based on the rehabilitation theory of continuous passive motion (CPM). To develop a CPM machine for the clinic application in the rehabilitation of injured fingers is a significant task. Therefore, based on the theories of evidence based medicine (EBM) and CPM, we've developed a set of biomimetic mechanism after modeling the motions of fingers and analyzing its kinematics and dynamics analysis. We also design an embedded operating system based on ARM (a kind of 32-bit RISC microprocessor). The equipment can achieve the precise control of moving scope of fingers, finger's force and speed. It can serves as a rational checking method and a way of assessment for functional rehabilitation of human hands. Now, the first prototype has been finished and will start the clinical testing in Harbin Medical University shortly. PMID- 17281374 TI - Robot-aided sensorimotor arm training methods based on neurological rehabilitation principles in stroke and brain injury patients. AB - We developed the upper extremity compound movements (UECM) rehabilitation training robot and designed straight-line paths tracking and circle paths tracking exercise based on neurological rehabilitation principles. Rehabilitative exercises should be on hand paths rather than on individual joints. robot can guide patients during forward reaching movements. The exterior oriented circle movement performed the coactivation of shoulder abductors with elbow extensors and the coactivation of shoulder adductors with elbow flexors at most of tracks against the stereotypic movement pattern in stroke and brain injury. PMID- 17281373 TI - A Haptic Interface Based on Potential Mechanical Energy to Investigate Human Motor Control using fMRI. AB - This paper describes a mechanical interface to use in conjunction with fMRI, in order to infer the brain mechanisms of human motor learning. Innovative mechanical concepts based on gravity and elastic forces were used to generate typical stable and unstable dynamic interactions at the hand during multijoint arm movements. Two designs were retained and implemented from MR compatible materials. The first uses a spring constrained between two specially designed surfaces and the other a capstan to transform the force induced by a groove carved on a shaft. These two degree-of-freedom mechanical interfaces have been constructed and tested. The use of a capstan mechanism was found to be limited by excessive friction, however, the method using a machined surface provides a simple and effective interface to investigate human motor control. PMID- 17281375 TI - An intelligent assistive robotic manipulator. AB - This paper presents the design of an automatic and intelligent robot arm for object grasping for people on wheelchair with mild to severe disabilities. The system is equipped with stereovision detection in order to distinguish different objects from the background. The robot arm has been designed with 6 degrees of action to grasp the detected object from the floor and bring it in front of the user. Two precalibrated digital cameras, facing downward, simultaneously take pictures of the surface where the object is located. Then by applying a new and robust 3D object detection method, the height, location and orientation of the object with respect to the robot's base point are found. The resulting rotation periods are transferred through a designated electronic driver board to the joints' motors via the PC parallel port. Overall, the system detects the object, moves the robot arm to the location of the object, grasps it, moves it to a predefined position in front of the user, releases the object and finally returns to its home position. The system is automatic and is operated by only one command. PMID- 17281377 TI - An embedded control system for intelligent wheelchair. AB - Due to recent advancement of AI and robotics technology, the research of intelligent wheelchair (iWheelChair) begins to draw attention from both scientific community and industry. iWheelchair is a kind of home welfare tools and can help the handicapped and elderly people to gain mobility and lead to independent life. This paper describes a newly developed intelligent wheelchair. The controller of the iWheelChair adopts the advanced DSP technology, and plays the role of data acquisition and processing of joystick and ultrasonic sensors. 8 ultrasonic sensors are mounted on iWheelchair and can detect the environment changes for safe operation. Experiments are presented to show that iWheelChair is able to avoid obstacles safely while controlled by its user via the joystick. PMID- 17281376 TI - Use of a novel robotic system for quantification of upper limb work area following stroke. AB - The effect of gravity on the expression elbow/shoulder synergy patterns results in discoordination during movements following stroke. This is believed to be related to the shoulder abduction torques generated when lifting the arm against gravity, which results in a concurrent elbow flexion (i.e., the flexion synergy). The Arm Coordination Training 3-D (ACT3D) robotic system is a novel way of recording movement patterns while a subject generates varying amounts of shoulder abduction torque. This system is used to provide preliminary results that show increased shoulder abduction forces reduce a stroke subject's available work area in a way that is consistent with the flexion synergy. Implications and clinical applications are briefly discussed. PMID- 17281378 TI - A novel robot neurorehabilitation for upper limb motion. AB - Our goal is to apply robotics and automation technology to assist, quantify, enhance, and verify neuro-rehabilitation. In this paper a novel robot neuro rehabilitation for upper limb, with many merits, is developed. Mechanism and control of the robot are introduced in detail. By a clinical trial involving 30 stroke patients with three months at Rehabilitation Center of China, some results are obtained 1) robot-aided therapy does not have adverse effects, 2) patients can accept the procedure, 3) the therapy may reduce muscular tension, and 4) manipulation of the impaired upper limb may influence brain recovery. Some new ideas are also presented to make rehabilitation therapy more effectively. These ideas will be helpful to further quicken the development of the robot neuro rehabilitation. PMID- 17281379 TI - Relation between patients' active force and effect of robotic therapy for rehabilitation. AB - In order to improve the effect of robotic rehabilitation therapy, we need to find out which elements of robot training influence it. Our aim is to analysis the relation between the patients-active force and the effect. This paper reviews a clinical therapy involving 6 hemiplegia patients with the upper extremity compound movements rehabilitation training robot developed by Tsinghua University, Beijing. By processing the collected data, we get the evidence that the elevated scores after training and the patients' active force are high correlated. The larger the patient's active force, the better the training effect. PMID- 17281380 TI - Fuzzy calibration of magnetometer in presence of surgical microscope. AB - A method is presented for data-driven calibration of the magnetometer in an active handheld microsurgical instrument in the presence of a surgical microscope. The instrument is designed to provide tremor compensation during vitreoretinal microsurgery. An adaptive-network-based fuzzy inference system is used to generate a calibration based on data points collected at random locations throughout the workspace. Inputs to the model include the tilt angle and the twist angle about the long axis of the instrument, obtained from accelerometer readings, and the azimuth of the apparent magnetic north, obtained from the magnetometer readings. The model outputs the true azimuth angle of the instrument. Results from preliminary testing of the method are presented. PMID- 17281381 TI - Research on micro robot for colonoscopy. AB - For diagnosing the colon's pathologies micro-invasively or non-invasively actively, an autonomous prototype of the earthworm-like robot for colonoscopy was designed according with the principle of the bionics and manufactured using precision process technology. In-Vitro experiments in pig colon were made. This micro robot for colonoscopy was drove directly by elecmagnetic linear driver. The mobile cells were joined with two degree-of-freedom joints and the whole body was flexible. The direction of movement and the angle of imaging can be controlled by the shape memory alloy (SMA). In experiments, locomotion efficient was analyzed carefully. In-vitro experiments in pig colon demonstrated that the micro robot can navigate though the colon by itself reliably and freely, which was useful to the application of robot for colonoscopy in the clinic. PMID- 17281382 TI - Design and development of a miniaturized 2-axis force sensor for tremor analysis during locomotion in small-sized animal models. AB - This work represents a first step towards the development of a sensorised environment for behavioral phenotyping of animal models. In particular, this paper focuses on tremor analysis in reeler mice, an emerging potential animal model for anatomical and behavioral traits observed in autism. Ground Reaction Force (GRF) sensing is indeed the most direct means of measuring tremor. Although force platforms have extensively been used for large size animals, only few attempts have been made to measure GRF at a single paw for animals as small as mice or rats. Under the hypothesis that in-plane GRF components are directly connected to tremor, a small size, low-cost, 2-axis force sensor for measuring the in-plane components of GRF was designed and developed. Special care was paid to allow self-aligned assembly for repeatability and modularity for combining multiple platforms for a sensorised floor. Preliminarily testing was performed with both reeler and wildtype mice. Fourier analysis was deployed to extract information due to tremor, validating the hypothesis of a direct connection between tremor and in-plane GRFs. PMID- 17281383 TI - Ultrasonic vibration microdissection system for molecular analysis of tissue. AB - Molecular techniques are transforming our understanding of cellular function and disease. However, accurate molecular analysis methods will be limited if the input DNA, RNA, or protein is not derived from pure population of cells or is contaminated by the wrong cells. Ultrasonic vibration microdissection provides the technology to procure pure population of targeted cells from tissue sections for subsequent analysis. It is a bio-manipulation system, which includes manipulator unit and control unit. Ultrasonic vibration microdissection is based on mechanical effect of ultrasound. We employed the multiplayer piezoelectric actuator for generating the ultrasonic vibration for cutting. With the help of ultrasound effect, an extremely fine microneedle was set in motion at a high frequency and low amplitude (approx. 16-50 kHz, and 0-3 mum) to cut the tissue. Experimental results show that embedded tissue, even thicker sections, can be quickly and precisely cut. Research indicates that Ultrasonic vibration microdissection is completely safe for DNA, RNA and protein analysis etc. PMID- 17281384 TI - A micro flow-meter for closed-loop management of biological samples. AB - The closed-loop management of biological samples in μTAS requires proper flow-sensors to be inserted in the hydraulic path. The optimal choice between hybrid mounting and monolithic fabrication depends on several design variables, one of which is the technological compatibility between the sensor and the pumping mechanism. Monolithic integration appears to be the eligible solution if both pumps and sensors can be fabricated with the same technological process. In this paper we show that it is actually possible to fabricate a flow-sensor, based on streaming potential detection, with the same soft-lithographic process used for the fabrication of electroosmotic pumps. The device has been fabricated in PDMS and experimentally tested, showing a good linearity. Finally, its time varying response, related to the aging of the PDMS surface, is discussed. PMID- 17281385 TI - A Novel Remote Controlled Capsule for Human Drug Absorption studies. AB - Remote Controlled Capsule (RCC) is a new method to realize non-invasive drug delivery to the selected sites of human gastro-intestinal (GI) tract. With RCC, Human Drug Absorption (HDA) studies are taken easily to obtain data on the intestinal absorption of a drug in humans. In this paper, a new RCC system has been designed based on MEMS technology to provide for the delivery of a wide range of different drug formulations, for example, solution, powder and granulate, into any region of the gut. A magnetic Marker Monitoring (MMM) system was developed to monitor the location of the capsule inside the gut. A novel method to indicating the drug release, called as Indicating System based on Abrupt Movement of Marker (ISAMM), was proposed in this study. High reliability of the RCC system has been proved by animal experiments. PMID- 17281386 TI - Photo-triggering of the membrane gates in photo-responsive polymer for drug release. AB - The use of light stimulus for triggering drug is a promising method for accurate drug delivery. A new approach using azopolymer membrane and laser holography was investigated for developing light-triggering drug delivery system. Polymeric drug delivery system was prepared by covering azopolymer membrane on a drug agent. Holographic laser interference generated surface relief grating pattern on the azopolymer surface. The widths and depths of gates on the polymer membrane were easily modified by adjusting incident angle and irradiation time. Ar laser made the polymeric membrane permeable to the drug agent and release it in a solution. This result indicated that the azopolymer and laser holography would provide a strong foundation for the light-triggering drug delivery system. PMID- 17281387 TI - Impact of the MRI-based Navigation System Constraints on the Step Response Using a PID Controller. AB - This paper presents the identification and the study of the impact of a real-time MRI-based propulsion and tracking system constraints on the step response using a discrete PID controller. A simplified model for such a system accounts for these constraints such as the time delay, the sampling period, and the blood velocity. This application is intended for minimally invasive operations within the human cardiovascular system. PMID- 17281388 TI - Comparative Quantification of Contractile Force of Cardiac Muscle Using a Micro mechanical Cell Force Measurement System. AB - In order to develop the cell based robot, we presented a micro-mechanical force measurement system for the biological muscle actuators, which utilize glucose as a power source for potential application in digestive organ. The proposed system is composed of a micro-manipulator, a force transducer with a glass probe, a signal processor, an inverted microscope and video recoding system. Using this measurement system, the contractile force and frequency of the cardiac myocytes were measured in real time and the magnitudes of the contractile force of each cardiac myocyte under different conditions were compared. From the quantitative experimental results, we could estimate that the force of cardiac myocytes is about 20~40 N, and show that there is difference between the control cells and the micro-patterned cells. PMID- 17281389 TI - An admittance control scheme for a robotic upper- limb stroke rehabilitation system. AB - This paper presents a control scheme for a dual robot upper-limb stroke rehabilitation system. A model of the human arm is outlined and used to formulate an admittance controller operating in human upper-limb joint space. Initial results are provided together with a discrussion of future work. PMID- 17281390 TI - Flexure-based Manipulator for Active Handheld Microsurgical Instrument. AB - This paper presents the design and initial experimental results of a flexure based parallel manipulator that is actuated by three piezoelectric stacks. The manipulator is for an active handheld tremor canceling device for microsurgery. By using flexures to approximate pin and ball joints, errors due to friction, backlash, and imperfect assemblies have been eliminated. The results show that the manipulator is capable of tracking motions similar to physiological tremor in amplitude and frequency. The workspace of the manipulator is more than 7 times larger than the tremor space in the x and y axes, and about 1.5 times larger in the z axis. One dimensional and three dimensional tracking tests had rms errors of 6.5 μm and 12.1 μm respectively. PMID- 17281391 TI - A functional cardiovascular model with disorders. AB - This paper introduces a functional model of the cardiovascular system that is capable of describing its behavior in normal as well as pathologic cases. The developed model includes all the main compartments of the circulatory system and also the baroreflex-feedback regulatory mechanism. The model response to the incorporation of two critical cardiovascular disorders namely hypertension and acute congestive heart failure is realistic and within the expected range of the results of the literature experimental data. PMID- 17281392 TI - Computationally predicting rate constants in pathway models. AB - The purpose of this project is to elucidate the kinetic parameters that govern a simulated sphingolipid metabolism system using various global optimization routines including Monte Carlo, Simulated Annealing, and Genetic Algorithms. Here a simulated 6-node system built from five UniUni reaction equations with known kinetic parameters. Each node was treated as a combination of single substrate - single product catalyzed reactions. This defined system of equations is then sampled at a rate that mimics the mass spectrometry measurements of the complex pathway in time shown in [1]. As the investigation on mathematical models of biological events continues to gain popularity, the use of global optimization methods to quickly and reliably estimate missing parameters will become more vital. This work investigates the use of global parameter estimation schemes in terms of their reliability to the true underlying kinetic parameters. When the amount of fitting parameters is sufficiently large, it is likely to find parameter sets that predict the data decently well but are not necessarily close to the true underlying parameters. PMID- 17281393 TI - Analysis of "scanner ferquency" noise in FMRI timeseries. AB - MRI system noise often appears in the fMRI timeseries in phantom and human subjects experiments. The predominant characteristic of this MRI system noise is high amplitude at one or a few specific temporal frequencies. These frequencies are immediately found by FFT analysis, but they have also been identified in ICA methods. This study indicates that these frequencies should be considered in the design of experimental paradigms and temporal digital filters. PMID- 17281394 TI - A new approach for magnetic resonance RF head coil design. AB - In this work, a new concept in high field RF head coil design for MRI applications is presented. An 8-element phased array head coil operating at 4T is designed based on a hybrid method combining reciprocity theorem and inverse method. Both circularly or linearly polarized head coils can be designed. A FDTD/MOM calculation method is used to model the phased array head coil and to accurately calculate the RF behavior inside a human head model. The simulation results reported herein demonstrate the feasibility and flexibility of the design concept and show that, compared to conventional methods, improved B1 field homogeneity is achievable at high field. PMID- 17281395 TI - The detection and visualization of brain tumors on T2-weighted MRI images using multiparameter feature blocks. AB - The objective of this paper is to present an analytical method to detect lesions or tumors in digitized medical images for 3D visualization. The authors developed a tumor detection method using three parameters; edge (E), gray (G), and contrast (H) values. The method proposed here studied the EGH parameters in a supervised block of input images. These feature blocks were compared with standardized parameters (derived from normal template block) to detect abnormal occurrences, e.g. image block which contain lesions or tumor cells. The abnormal blocks were transformed into three-dimension space for visualization and studies of robustness. Experiments were performed on different brain disease based on single and multiple slices of the MRI dataset. The experiments results have illustrated that our proposed conceptually simple technique is able to effectively detect tumor blocks while being computationally efficient. In this paper, we present a prototype system to evaluate the performance of the proposed methods, comparing detection accuracy and robustness with 3D visualization. PMID- 17281396 TI - Zero-crossing iso-surfaces in volume datasets. AB - This paper describes a new surface extraction method for volume datasets by applying iso-surface extraction techniques to the zero-crossing edges in a volumetric domain. A volume dataset is first filtered using a Laplacian of Gaussian filter to generate a zero-crossing field. A marching cube process will then be able to extract the entire zero-crossing surface that may be viewed selectively based on various intensity ranges and gradient scales. This new technique provides a more efficient surface navigation and extraction mechanism, as well as more accurate surface details, than the traditional iso-surface techniques. PMID- 17281397 TI - Coordinate systems integration for development of malaysian craniofacial database. AB - This study presents a data registration method for craniofacial spatial data of different modalities. The data consists of three dimensional (3D) vector and raster data models. The data is stored in object relational database. The data capture devices are Laser scanner, CT (Computed Tomography) scan and CR (Close Range) Photogrammetry. The objective of the registration is to transform the data from various coordinate systems into a single 3-D Cartesian coordinate system. The standard error of the registration obtained from multimodal imaging devices using 3D affine transformation is in the ranged of 1-2 mm. This study is a step forward for storing the spatial craniofacial data in one reference system in database. PMID- 17281398 TI - Interactive Segmentation of Muscles and 3D Representation of Meridians Based on Visible Human. AB - Based on VOXEL-MAN software and our previous work on merging acupoint information with the dataset of the male Visible Human, we have refined the segmentation method for muscles and visualized the anatomical structure of meridians. In interactive segmentation, we obtain additional information on connectivity and texture. We also apply surface fitting to track muscle contours on data slices where the threshold segmentation method is hard or impossible to apply. With these processes, the original segmentation method, mainly via threshold, is improved to deal with more complex situations. We also constructed meridians, which are supposed to be composed by groups of acupoints. For that we used the location of these acupoints and interpolation methods. PMID- 17281399 TI - Spine-based coordinate system. AB - Traditional techniques for analyzing tortuous anatomical structures (e.g. arteries, colon, spine) in the coordinate system of the 3D image generally do not provide sufficient or qualitative enough diagnostic information, because planar cross-sections do not follow curved paths along the structures. To overcome this shortcoming, images in the coordinate system of the structure must be created. We propose a transformation from standard image-based to a novel spine-based coordinate system. The origin and axes of the proposed spine-based coordinate system are determined on the curve that represents the vertebral column, and the rotation of the vertebrae around the spine curve, both of which are described by polynomial models. The optimal polynomial parameters are obtained in an image analysis based optimization framework. The method has been evaluated on five CT spine images. PMID- 17281400 TI - Haptic rendering of volumetric data for cranial implant modeling. AB - A force feedback algorithm for cranial implant design is presented in this paper. The algorithm is applied directly on volumetric data. It is a proxy-based algorithm, and a spherical proxy is used to accurately calculate the force between the sculpting tool and the skull. Based on this algorithm a cranial implant modeling system is implemented, and an implant for a simulated defect is designed. PMID- 17281401 TI - Simulation of eye disease in virtual reality. AB - It is difficult to understand verbal descriptions of visual phenomenon if one has no such experience. Virtual Reality offers a unique opportunity to "experience" diminished vision and the problems it causes in daily life. We have developed an application to simulate age-related macular degeneration, glaucoma, protanopia, and diabetic retinopathy in a familiar setting. The application also includes the introduction of eye anatomy representing both normal and pathologic states. It is designed for patient education, health care practitioner training, and eye care specialist education. PMID- 17281402 TI - Viewing interfaces for segmentation and measurement results. AB - In the paper we describe a web-based interface to view 2-D and 3-D results generated from segmentation and measurement process interactively. Our implementation takes a fully web-based approach to provide universal access and visualization to a wide range of patient data (i.e. at multiple locations). An example case study is presented: thickness measurement of articular cartilage from MR knee images used in the diagnosis of osteoarthritis (OA). PMID- 17281403 TI - A computerized simulation system of mandibular movement on Hanau articulator. AB - The purpose of this study is to solve the problems that lie in the current research on mandibular movement and dynamic occlusion of complete denture in the field of dental restoration. On the basis of the theory of spatial mechanisms, the displacement matrix of mandibular movement on Hanau articulator is established through the method of direction cosine matrix. By adopting techniques such as laser scanning, computer graphics, and computer database, a 3D digitized model of maxillary and mandibular body is reconstructed, and then a computerized simulation system of mandibular movement is developed. With the aid of this software, the geometrical locus of an arbitrary landmark on maxillary denture can be plotted, the visualization and diagnosis of mandibular movement can be easily realized and the information concerned with the positions and number of the occlusal contacts can be obtained. One edentulous case is taken as an example in this article. The results show this study provides a useful tool to deal with the functional aspects of occlusal morphology in a diagnostical and therapeutical sense. PMID- 17281404 TI - Improved Diagnosis and Navigation for CT Colonography. AB - The goal of this research project is to develop a fast, accurate, and patient friendly computer-aided diagnosis (CAD) component of CT colonography, that improves the robustness and accuracy of current colon wall segmentation and achieves earlier colorectal cancer diagnoses through an improved polyp detection method. Many advanced image processing techniques are applied to clearly outline the colon wall in the CT data set of human abdomen, and subtract the colon portion from the entire data set. After the subtraction, the detailed information and the surface curvature information on the colon wall is analyzed. The active contour model is assisted by presegmentation steps including mathematical morphology filtering, edge detection and other image processing techniques. PMID- 17281405 TI - GPU-based Volume Rendering for Medical Image Visualization. AB - During the quick advancements of medical image visualization and augmented virtual reality application, the low performance of the volume rendering algorithm is still a "bottle neck". To facilitate the usage of well developed hardware resource, a novel graphics processing unit (GPU)-based volume ray casting algorithm is proposed in this paper. Running on a normal PC, it performs an interactive rate while keeping the same image quality as the traditional volume rendering algorithm does. Recently, GPU-accelerated direct volume rendering has positioned itself as an efficient tool for the display and visual analysis of volume data. However, for large sized medical image data, it often shows low efficiency for too large memories requested. Furthermore, it always holds a drawback of writing color buffers multi-times per frame. The proposed algorithm improves the situation by implementing ray casting operation completely in GPU. It needs only one slice plane from CPU and one 3Dtexture to store data when GPU calculates the two terminals of the ray and carries out the color blending operation in its pixel programs. So both the rendering speed and the memories consumed are improved, and the algorithm can deal most medical image data on normal PCs in the interactive speed. PMID- 17281406 TI - An automatic and fast centerline extraction algorithm for virtual colonoscopy. AB - This paper introduces a new refined centerline extraction algorithm, which is based on and significantly improved from distance mapping algorithms. The new approach include three major parts: employing a colon segmentation method; designing and realizing a fast Euclidean Transform algorithm and inducting boundary voxels cutting (BVC) approach. The main contribution is the BVC processing, which greatly speeds up the Dijkstra algorithm and improves the whole performance of the new algorithm. Experimental results demonstrate that the new centerline algorithm was more efficient and accurate comparing with existing algorithms. PMID- 17281407 TI - Prostatectomy Evaluation using 3D Visualization and Quantitation. AB - Prostate cancer is a disease with a long natural history. Differences in survival outcomes as indicators of inappropriate surgery would take decades to appear. Therefore, the evaluation of the excised specimen according to defined parameters provides a more reasonable and timely assessment of surgical quality. There are currently a number of very different surgical approaches. Some uniform guidelines and quality assessment measuring readily available parameters would be desirable to establish a standard for comparison of surgical approaches and for individual surgical performance. In this paper, we present a novel methodology to objectively quantify the assessment process utilizing a 3D reconstructed model for the prostate gland. To this end, we discuss the development of a process employing image reconstruction and analysis techniques to assess the percent of capsule covered by soft tissue. A final goal is to develop software for the purpose of a quality assurance assessment for pathologists and surgeons to evaluate the adequacy/appropriateness of each surgical procedure; laparoscopic versus open perineal or retropubic prostatectomy. Results from applying this technique are presented and discussed. PMID- 17281408 TI - Virtual Laryngoscopy: A Real-Time Exploration of Laryngeal System based on Rapid Reconstruction Algorithm. AB - In this paper, we present a real-time approach for effective and automatic manipulation and navigation in a virtual laryngeal environment. Efficient algorithms are developed for 1), automatic segmentation, and 2) volume data organization and 3), surface rendering. Finally a virtual laryngoscope is built for the visualization of laryngeal systems and this visualization system is tested using CT volume data acquired from two normal subjects. PMID- 17281409 TI - Fast volume rendering for medical image. AB - In orders to improve the rendering speed of ray casting and make this technique a practical routine in medical applications, two new and improved techniques are described in this paper. First, an integrated method using "proximity clouds" technique is applied to speed up ray casting. The second technique for speeding up the 3D rendering is done through a parallel implementation based on "single computer multi CPU" model Four groups of CT data sets have been used to validate the improvement of the rendering speed. The result shown that the interactive rendering speed is up to 6-10 fps, which is almost real-time making our algorithm practical in medical visualization routine. PMID- 17281410 TI - A research on the hospital intranet-based three-dimensional image assisted diagnosis system. AB - We discuss the composition of the medical image data transmission and three dimensional visualization system, probe into the related technical details about realizing the system functions, and summarize several key aspects dealing with the realization of telemedicine. By virtue of the DICOM3.0 standard, the image data compatibility problem concerning the transmission of medical image data was solved, realizing the functions of two-dimensional image processing and three dimensional visualization of medical image data, and facilitating the increasing of clinically diagnostic veracity and efficiency. PMID- 17281411 TI - Construction of volume meshes from computed tomography data. AB - In this paper, we present a new method, called marching volume elements (MVE), for automatically constructing a volume mesh from three-dimensional (3-D) high resolution computed tomography (CT) data. The volume mesh generated by the MVE algorithm is suitable for computational fluid dynamics (CFD) simulations. The MVE algorithm is based on the marching cubes (MC) algorithm which is a surface generation algorithm for 3-D intensity data. The mesh created with the MVE algorithm is composed of pyramids, cubes and tetrahedrons with common faces that fit together to form a topologically consistent volume. We validate the MVE algorithm on a synthetic object and demonstrate it on CT scans of a human nasal cavity. PMID- 17281412 TI - Parallel visualization of visible chinese human with extremely large datasets. AB - Single sectional anatomy image of Visible Chinese Human datasets achieved recently in First Military Medical University is almost 127MByte. The total datasets are estimated to be 1.1 TByte if 48 bits color image is stored. Personal computer and graph workstation with multiple CPUs are also impossible to process extremely large datasets. Therefore the challenge is to visualize the extremely large datasets efficiently. Visible Chinese Human datasets are so massive in size they require the use of parallel computing resources for effective visualization. At present a parallel visualization program has been developed based on parallelism visualization toolkit (pVTK) on high performance cluster to solve the problem. The visualization results and performance demonstrate that the parallel program we developed provides a promising solution of handling extremely large datasets. PMID- 17281413 TI - Time synchronization in wireless physiological information sensor network. AB - Time synchronization is necessary to a Wireless Sensor Network (WSN). Existing time synchronization methods are mostly designed for large scale ad hoc network and are not suitable for small star network like Wireless Physiological Information Sensor Network (WPISN). In this article we present a simple and power efficient time synchronization method designed specially for WPISN, Reference on Demand Time Synchronization method (RDTS), which employs the Near-Field Magnetic Communication (NFMC) technology. NFMC offers significant power, cost, and size advantages over RF communication. PMID- 17281414 TI - Microcontroller-based wireless recorder for biomedical signals. AB - A portable multichannel system is described for the recording of biomedical signals wirelessly. Instead of using the conversional time-division analog modulation method, the technique of digital multiplexing was applied to increase the number of signal channels to 4. Detailed design considerations and functional allocation of the system is discussed. The frontend unit was modularly designed to condition the input signal in an optimal manner. Then, the microcontroller handled the tasks of data conversion, wireless transmission, as well as providing the ability of simple preprocessing such as waveform averaging or rectification. The low-power nature of this microcontroller affords the benefit of battery operation and hence, patient isolation of the system. Finally, a single-chip receiver, which compatible with the RF transmitter of the microcontroller, was used to implement a compact interface with the host computer. An application of this portable recorder for low-back pain studies is shown. This device can simultaneously record one ECG and two surface EMG wirelessly, thus, is helpful in relieving patients' anxiety devising clinical measurement. Such an approach, microcontroller-based wireless measurement, could be an important trend for biomedical instrumentation and we help that this paper could be useful for other colleagues. PMID- 17281415 TI - Wireless sensor and data transmission needs and technologies for patient monitoring in the operating room and intensive care unit. AB - In the intensive care unit, or during anesthesia, patients are attached to monitors by cables. These cables obstruct nursing staff and hinder the patients from moving freely in the hospital. However, rapidly developing wireless technologies are expected to solve these problems. To this end, this study revealed problem areas in current patient monitoring and established the most important medical parameters to monitor. In addition, usable wireless techniques for short-range data transmission were explored and currently employed wireless applications in the hospital environment were studied. The most important parameters measured of the patient include blood pressures, electrocardiography, respiration rate, heart rate and temperature. Currently used wireless techniques in hospitals are based on the WMTS and WLAN standards. There are no viable solutions for short-range data transmission from patient sensors to patient monitors, but potentially usable techniques in the future are based on the WPAN standards. These techniques include Bluetooth, ZigBee and UWB. Other suitable techniques might be based on capacitive or inductive coupling. The establishing of wireless techniques depends on ensuring the reliability of data transmission, eliminating disturbance by other wireless devices, ensuring patient data security and patient safety, and lowering the power consumption and price. PMID- 17281416 TI - A PDA-based Network for Telemonitoring Asthma Triggering Gases in the El Paso School Districts of the US - Mexico Border Region. AB - In this paper we describe the application of a personal digital assistant (PDA) or pocket PC as an effective communication device to telemonitor levels of asthma triggering gases collected from a remote location under test to a workstation which has a personal computer (PC) running on Windows XP® as the operating system. The Bluetooth® features of the PDA are explored to transmit data collected by a Direct™ Sense Tox toxic gas monitor equipped with five toxic gas probes and one temperature sensor in real time, thereby making this telemonitoring system an innovative instrument in monitoring levels of asthma triggering gases in the El Paso-border metropolitan region, a region in which asthma is highly prevalent especially in children. At the workstation or fixed location these readings are displayed using a custom made, user friendly graphical user interface (GUI) developed using software tools like action scripting with Macromedia® Flash™. The growing advancement in technology and ever diminishing sizes of handheld devices encouraged us to opt for this configuration. Moreover, the PDA and toxic gas monitor were also chosen for their light weight, portability, flexibility, low cost and data collection and transmission capabilities. PMID- 17281417 TI - Real-time Magnetic Resonance Gradient-based Propulsion of a Wireless Microdevice Using Pre-Acquired Roadmap and Dedicated Software Architecture. AB - A new method for the propulsion of a spherical ferromagnetic device along a given path in a water filled phantom with no human interaction is presented using an 1.5 T Magnetic Resonance Imaging (MRI) clinical system. A special real time loop is implemented and presented that feeds the scanner with the appropriate gradients amplitudes and directions based on a pre-determined path. This paper studies the necessary propulsion conditions and limitations such as device dimensions and necessary gradient amplitude as well as overall latency problems such as communication delays and computation delays needed to achieve precise propulsion. It also presents a dedicated software environment for path control and validation, propulsion and tracking of such device. PMID- 17281418 TI - Implantable RF power converter for small animal in vivo biological monitoring. AB - A miniature, long-term, implantable radio frequency (RF) power converter for freely moving samll animal in vivo biological monitoring is proposed. An environment consisting of a laboratory mouse inside a cage is used for a prototype monitoring system design. By employing an inductive coupling network, a prototype implant device with a dimension of approximately 6 m x 6 mm x 1 mm and a weight of 100 mg including medical-grade silicone coating can wirelessly receive an input FR power from an array of external coils positioned underneath the cage. Each coil is designed to be 5 cm x 5 cm, comparable to a typical mouse size for minimizing power coupling variation. The received AC voltage is further rectified by a half-wave rectivier to supply DC current to a 3 kω resistance, representing a typical bio-implant microsystem loading. The proposed RF power converter was implanted in the peritoneal cavity of a laboratory mouse for performance evaluation. With a 5-turn external coil loop separated from a 30 turn internal coil by 1cm distance and centered to each other, an optimal voltage gain of 3.5 can be achieved with a 10 MHz operating frequency to provide a maximum rectified output DC voltage of 21 V. The DC voltage varies at different animal tilting angles and positions with a minimum voltage of 4 V at 60° tilting angle near the corner of the external coil. This variation can be further minimized by overlapping the external loops layout. PMID- 17281419 TI - Simulation and Analysis of 2D Magnetic Field of Capsule Endoscope. AB - 2D magnetic field of a device used in the micropump of capsule endoscope is analyzed and calculated. Magnetic torque is simulated when the coils and permanent magnet are in different relative positions. The torque is calculated too when strength of external rotational magnetic field is changed. Corresponding results provide theoretical guide to the design and development of device. PMID- 17281420 TI - Classification Technique of Human Motion Context based on Wireless Sensor Network. AB - The fusion technology of small sensor and wireless communication was followed by various application examples of the embedded system, where the social infrastructural facilities and ecological environment were wirelessly monitored. In the paper, new monitoring and classifying method of human motion context was proposed by using 2-axial MEMS accelerometer and 916 MHz short range data communication technology. During four types of subjects motion, waveform changes of the accelerometer data was acquired by wireless sensor network, then analyzed by principal component analysis (PCA) and support vector machine (SVM) method for clustering the first and second principal components. To classify the subjects motion type, supervised learning method was used for segmentation algorithm. The present study showed that the developed algorithm could classify four types correctly. Therefore, human motion context during daily life could be monitored and classified by using wireless sensor network. PMID- 17281421 TI - Method of measuring calorie consumption for portable apparatus. AB - A measuring device for use in measuring calorie consumption includes a pulse input unit which detects a first heart rate of the user at a first point in an exercise period and a second heart rate of the user at a second point of the exercise period other than the first point, the pulse input unit not detecting a third heart rate between the first and second heart rates; and a controller which receives the detected first and second heart rates and calculates calories consumed using the detected first heart rate, the detected second heart rate, an at rest heart rate of the user, and one or more of an age, gender, weight, height and an at rest heart rate of the user. The measuring device is usable in a portable device, such as a portable digital audio and/or video reproducing apparatus. PMID- 17281422 TI - Heart Rate Monitor for Portable MP3 Player. AB - This paper presents a photoplethysmography sensor based on a heart rate monitor for a portable MP3 player. Two major design issues are addressed: one is to acquire the sensor signal with a proper amplitude despite a wide range of variation and the other is to handle the noise contaminated signal which is caused by a motion artifact. A benchmarking test with a professional medical photoplethysmography sensor shows that our device performs very well in calculating heart rate even though our photoplethysmography sensor module was designed to be cost effective. PMID- 17281423 TI - Enhancing the precision of infrared thermodetector for medicine by two-channel measuring technique and mulriple linear interpolation algorithm. AB - The best way to control the spread of Severe Acute Respiratory Syndrome (SARS) is measuring the body temperature precisely, therefore, it is very important to develop a set of high-precision infrared thermodetector for Medicine. The ambient temperature signal and the object temperature signal were collected with two channel AD gates of thermopile infrared sensor unit. The values were calculated by using mulriple linear interpolation algorithm. The precision of the system can reach 0.1°C and the machine can work well in megathermal environment*. PMID- 17281424 TI - Neurobiochemistry and neuroelectrophysiology of neuron-like cells differentiated from neural BMSCs-D-NSCs. AB - In this experiment, the bone marrow stroma cells (BMSCs) were harvested and then cultured in "neural stem cells (NSCs) medium" which was modulated by our lab with P. R. of China patent number as ZL 02134314.4 in vitro. The proliferation of NSCs was confirmed by formation of cell's clones and scan electron microscopy test. The identifications of NSCs, neurons-like cells and glial-like cells were immunocytochemically performed by detecting Nestin, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP). Neurons-like cells were further identified by detecting excitability amino acid, inhibited amino acid, or monoamine biological activity materials with high pressure liquid chromatograph (HPLC), and also by examining the electrophysiological properties with patch clamp, in order to verify their neuron-like functions. It was implied that the differentiated BMSCs-NSCs-derived neuron-like cells were characterized by both the neuron-like bio-chemical function and some corresponding electrophysiological properties. PMID- 17281425 TI - Facial recognition using enhanced pixelized image for simulated visual prosthesis. AB - A simulated face recognition experiment using enhanced pixelized images is designed and performed for the artificial visual prosthesis. The results of the simulation reveal new characteristics of visual performance in an enhanced pixelization condition, and then new suggestions on the future design of visual prosthesis are provided. PMID- 17281426 TI - Prosthetic visual acuity in irregular phosphene arrays under two down-sampling schemes: a simulation study. AB - To investigate the effects of phosphene array irregularity in visual prostheses, a model of phosphenes' positional uncertainty was devised and two different image down-sampling schemes, adapting and non-adapting, were proposed. Based on a simulation system, visual acuity tests were given to four normally sighted subjects under seven degrees of array irregularity and the two down-sampling schemes. With the irregularity index increasing from 0 to 0.6, visual acuity fell over a range of 0.22 logMAR (logarithm of minimum angular resolution) for the adapting scheme and 0.47 logMAR for the non-adapting scheme, both monotonously. Comparison between the two down-sampling schemes was made. For low array irregularity, non-adapting down-sampling afforded higher visual acuity, whereas for higher irregular the adapting approach did. Head movements were observed to play significant roles in the acuity tests. PMID- 17281427 TI - Influence of Shoe-heel Height of the Trans-tibial Prosthesis on Static Standing Biomechanics. AB - Shoe-heel height has great influence on lower-limb amputees' biomechanics during static standing. This article mainly considers the load line of the prosthetic side in the sagittal plane and the electromyogram (EMG) data of the lower limb muscles. The results indicate that the load line and the EMG are greatly influenced by the shoe-heel height, however, the amputee subconsciously adjusts his standing manner to make himself more comfortable and natural. This will provide references for prosthesis design and alignment setting. PMID- 17281428 TI - Peripheral somatosensory stimulation induced cortical plasticity and its clinical application on functional restoration in chronic stroke. PMID- 17281429 TI - A programmable discharge circuitry with current limiting capability for a retinal prosthesis. AB - Biphasic stimulation is the most commonly used electrical pattern in FES (Functional Electrical Stimulation). In such cases, a charge balanced waveform is essential to prevent any charge accumulation in the biological tissue. In a retinal prosthesis, a charge cancellation circuitry is used to discharge the stimulation sites on the retina periodically to ensure tissue safety. But discharging a node that has high voltage (due to charge accumulation) will induce large currents that might lead to unintended stimulation of the retina. This paper presents a new discharge circuitry which can act as a simple resistive discharge path for smaller voltages and a current limiter for higher voltages. In stimulation circuits which use a dual voltage scheme (positive and negative), the circuit limits the current at both polarities. The discharge profile is programmable digitally. In addition, a method to characterize inter-pixel leakage in a retinal prosthesis using this circuit is proposed. PMID- 17281430 TI - A wireless phase shift keying transmitter with q-independent phase transition time. AB - Inductive coupling is a common way to wirelessly transmit data to medical implants. In such applications, the carrier frequency is often limited to tens of MHz which is able to well penetrate the skin. To achieve high data rate, the number of carrier cycles used to modulate each bit should be as small as possible. This usually requires lowering the quality factor (Q) of the data transmission network, resulting in increased power dissipation. This paper presents a novel data transmitter using phase shift keying which can modulate the phase of the carrier within two carrier cycles, independent of the Q of the network; thus low power dissipation can be achieved. The transmitter is designed by taking advantage of the multiplefrequency resonant network of class-E power amplifiers. Design guidelines for such a Q-independent phase modulator are provided. Simulations and experimental results demonstrate that the phase modulator functions as expected. PMID- 17281431 TI - Current distribution during parallel stimulation: implications for an epiretinal neuroprosthesis. AB - A simplified mathematical model has been developed in order to better understand local current spread when multiple simultaneous current sources are used in an epiretinal neuroprosthesis. To test the model, pairs of platinum electrodes of 430 μm diameter and an intra-pair spacing of 1 mm between centers, were arranged either in-line or in parallel, in a bath of physiological saline. Each pair was separated by distances from 1 mm to 6 mm. The currents in each electrode in the bath were measured and compared with the computational model of the same arrangement. This approach allowed us to quantify return current interaction between parallel sources. As predicted, with parallel electrodes and matching currents in each electrode pair, there is no current cross-talk. However with imbalanced current sources, significant cross-talk is evident. The cross-talk decreases as a function of electrode pair separation. The implication of this work in the design of an epiretinal neuroprosthesis is discussed. PMID- 17281433 TI - Fully Integrated and Low Power CMOS Amplifier for Neural Signal Recording. AB - This paper presents a fully integrated and low power CMOS amplifier for neural signal recording. It consists of a band-filtering preamp and a current-mode instrumentation amplifier. The design approach and the noise optimizing are briefly discussed. A 0.6 μm CMOS technology is used for the design of the amplifier IC. The simulation shows that it has a pass band from 59Hz to 12.8 kHz and a mid-band gain of 80 dB. The supply voltage is ±1.25V and the power consumption is 180µW. PMID- 17281432 TI - Comprehensive Cyclic Voltammetry Characterization of AIROF Microelectrodes. AB - Cyclic voltammetry (CV) at slow scan rate is usually performed to characterize the electrochemical behavior of microelectrodes. Early in vitro study on over 200 activated iridium oxide film (AIROF) microelectrodes showed variability of their electrochemical behavior. In this paper, we reported CV measurements under 3 different scan rates for 96 AIROF microelectrodes. We traced their behavior during 7 stages of fabrication and processing starting from prior to activation, and ending with post-implantation in the experimental animal. The results show that even at the early stage of electrode activation, variations between near identical electrodes existed. PMID- 17281434 TI - Neural prosthesis for obstructive sleep apnea. AB - Electrical stimulation of the hypoglossal (XII) nerve has been demonstrated as an effective approach to treating obstructive sleep apnea (OSA). The physiological effects of conventional modes of stimulation (i.e., genioglossus activation or whole XII nerve stimulation), however, have yielded inconsistent and only partial alleviations of hypoapneic or apneic events. While selective stimulation of the multi-fasciculated XII nerve offers many stimulus options, it is not clear how they will functionally affect the upper airway (UAW). To study these effects, animal experiments in four beagles were performed to investigate changes in critical pressure (Pcrit), during inspiration. For simulated inspiration, only whole XII nerve stimulation (-0.9 ± 0.4 cmH2O) and co-activation of the GG + HG/SG muscles (-1.18 ± 0.6 cmH2O) produced significant (p < 0.05) improvements in UAW stability (i.e., lowered Pcrit), compared to baseline (-0.52 ± 0.32 cmH2O). The results of this study suggest that a multi-contact nerve electrode can achieve both UAW dilation and patency, comparable to that obtained with non-selective stimulation by selectively activating the various branches of the XII nerve. PMID- 17281435 TI - A Cochlear Implant System with Infra-red Telemetry for Behaving Animals. AB - A new cochlear implant system for animal experiments is proposed. The system uses a DSP-based sound processor to implement the six-channel continuous interleaved sampling (CIS) speech processing strategy. An infra-red telemetry is designed to remotely connect the power-demanding sound processor to receiver/stimulator attached on the animal. This enables the animal to move freely. The receiver/stimulator consumes about 40mW, thus can operates for about 200hours without changing battery. PMID- 17281436 TI - Micromachined electrode arrays with form-fitting profile for auditory nerve prostheses. AB - This paper reports the design, fabrication and simulation of a novel micromachined electrode array with a form-fitting profile for use in auditory nerve prostheses. A 10times10 electrode array is created in a 1mm2 area using bulk micromachining technology. The space between the individual electrodes within the array is filled with a layer of SU-8 molded to conform to the curved surface of the auditory nerve. This layer enables the implant to be secured to the auditory nerve and to have a good sealing between the array and the nerve tissue after insertion. An electrical model for a single electrode is built. Both mechanical and electrochemical finite element analyses (FEA) of the array are also performed. PMID- 17281437 TI - A proposed intracortical visual prosthesis image processing system. AB - It has been a goal of neuroprosthesis researchers to develop a system, which could provide artifical vision to a large population of individuals with blindness. It has been demonstrated by earlier researches that stimulating the visual cortex area electrically can evoke spatial visual percepts, i.e. phosphenes. The goal of visual cortex prosthesis is to stimulate the visual cortex area and generate a visual perception in real time to restore vision. Even though the normal working of the visual system is not been completely understood, the existing knowledge has inspired research groups to develop strategies to develop visual cortex prosthesis which can help blind patients in their daily activities. A major limitation in this work is the development of an image proceessing system for converting an electronic image, as captured by a camera, into a real-time data stream for stimulation of the implanted electrodes. This paper proposes a system, which will capture the image using a camera and use a dedicated hardware real time image processor to deliver electrical pulses to intracortical electrodes. This system has to be flexible enough to adapt to individual patients and to various strategies of image reconstruction. Here we consider a preliminary architecture for this system. PMID- 17281438 TI - An FPGA-Based Vision Prosthesis Prototype: Implementing an Efficient Multiplexing Method for Addressing Electrodes. AB - A prototype of an epi-retinal vision prosthesis based upon an efficient electrode addressing schema has been developed. This system has the ability to stimulate multiple electrode regions simultaneously, hence greatly improving the maximum rate of stimulation compared to many currently available neural stimulation devices based on serial stimulation protocols. To minimize the problem of cross talk between stimulating electrodes, a hexagon layout of electrodes was implemented. Basic tests were completed using a field programmable gate array logic system driving analogue circuitry to inject current into physiological saline via electrodes in hexagon arrangements and in a simple paired arrangement. The hexagon layout of electrodes was shown to clearly reduce the interaction between multiple current sources and hence cross talk. PMID- 17281440 TI - Elimination of ECG Artifacts from Myoelectric Prosthesis Control Signals Developed by Targeted Muscle Reinnervation. AB - We investigated elimination of electrocardiogram (ECG) artifacts from the myoelectric prosthesis control signals, taken from the reinnervated pectoralis muscles of a patient with bilateral amputations at shoulder disarticulation level. The performance of various ECG artifact removal methods including high pass filtering, spike clipping, template subtracting, wavelet thresholding and adaptive filtering was presented. In particular, considering the clinical requirements and memory limitation of commercial prosthesis controllers, we further explored suitable means of ECG artifact removal for clinical application. PMID- 17281441 TI - Advantage of support vector machine for neural spike train decoding under spike sorting errors. AB - Decoding of kinematic variables from neuronal spike trains is important for neuroprosthetic devices. The spike trains from single units must be extracted from extracellular neural signals and thus spike detection and sorting procedure is essential. Since the spike detection and sorting procedure may yield considerable errors, decoding algorithm should be robust against spike train errors. Here we showed that the spike train decoding algorithms employing a nonlinear mapping, especially support vector machine (SVM), may be more advantageous contrary to conventional belief that linear filter is sufficient. The advantage became more conspicuous with erroneous spike trains. Using the SVM, satisfactory performance could be obtained much more easily, compared to the case of using multilayer perceptron, which was employed for previous studies. The results suggests the possibility of neuroprosthetic device with a low-quality spike sorting preprocessor. PMID- 17281439 TI - Multifunctional flexible parylene-based intracortical microelectrodes. AB - Delivering drugs directly to the brain tissue opens new approaches to disease treatment and improving neural interfaces. Several approaches using neural prostheses have been made to deliver drugs directly with bypassing the blood brain barrier (BBB) [1, 2]. In this paper, we propose a new polymer-based flexible microelectrode with drug delivery capability. The probe was fabricated and tested for electrical and fluidic functionality in early stage design. In vivo chronic recording experiments succeeded in demonstrating the in vivo reliability of the probe. Successful in vivo experiments confirm the suitability of the probes as implantable chronic recording devices with robust fluid delivery function. PMID- 17281442 TI - An auditory vigilance task for mental fatigue detection. AB - An Auditory Vigilance Task (AVT) as a validation criterion for monitoring mental fatigue was proposed in this study. The biological basis of this task design is on the understanding that mental fatigue is a cortical deactivation. This AVT is simple to perform, free of learning curve and independent on acquired skills (aptitude, knowledge). The validity and sensitivity of this task was verified by a scientifically controlled 25-hour fatigue experiment recorded by Electroencephalogram (EEG). Results showed that this AVT is highly sensitive to changes during fatigue process. The effectiveness of this AVT was compared to one subjective rating scale (FSS). The 5-level fatigue EEG datasets (labeled by AVT and FSS respectively) were fed into Support Vector Machines (SVM). SVM test accuracy indicated that AVT is more effective than subject's own estimation. The results demonstrate conclusively that this AVT is suitable for fatigue detection study as a reliable validation criterion. PMID- 17281443 TI - Function electrical stimulation signals generator circuits for the central nerve and the sciatic nerve. AB - Circuits for the signal generation of the FES (functional electrical stimulation) of the central nerve and the sciatic nerve have been designed. The circuits were implemented by using discrete devices. The FES circuits consist of two or three operational amplifiers. The bandwidths of the circuits are more than 10 kHz and their gains are variable from 20 dB to 60 dB. To a load of several kilo-ohms, according to the microelectrode with the nerve, the circuit for stimulating central nerve can provide a current signal, and the signal value is more than 1mA. The circuit for stimulating sciatic nerve can provide a stimulating voltage signal of more than 10 Vs. The loads of the circuits are microelectrodes contacted with nerves. The circuits can be used with two kinds of microelectrodes: cuff microelectrodes which for stimulating sciatic nerve and shaft microelectrodes which for stimulating central nerve. PMID- 17281444 TI - Analysis of functional MRI data during continuous rest state sequently using time series and spatial clustering: A primary study. AB - The aim of the present study is to develop a method to detect the neural activity during rest state from fMRI data. According to the high functionally neural connectivity and spatial relationship of a functional group of brain, time series and spatial clustering are sequently applied to detect the functional groups. In the article, the author also discusses the validation of the method applied to surrogate data. PMID- 17281446 TI - The mean intensity ofo activation than the number of activated voxels is a better index to reflect the levels of visuospatial performance. AB - This study is to identify the more sensitive method to measure the brain activation by the visuospatial performance level by comparing two different methods of measuremtnt (i.e., a method calculating the number of activated voxels and the other, the mean intensity of activated voxels). Sixteen right-handed male college students (mean age 23.2 years) participated in this study and function brain images were scanned with a 3T MRI using the single-shot EPI method during visuospatial performance. There found no brain areas with correlation between the visuospatial performance level and number of activated voxels. However, there found a sifgnificant correlatgion between the visuospatial performance level and the mean intensity of selected activated voxels in the parietal, frontal, and other areas.f In conclusion, the method of meanintensity rather than the one of the number is considered as a better index. PMID- 17281445 TI - The study of edge detection of cerebrovascular image based on gabor filter. AB - In order to analyze and process the cerebrovascular image, we research the frame characteristic of the filter's imaginary part based on the analysis of the basic character of the Gabor filter algorithm. In detecting the edge of cerebrovascular image, we introduce the imaginary part of the Gabor filter algorithm as the new image characters of cerebrovascular image, and get a better experiment result by using the analysis strategy of weighted average. At the same time, in order to accelerate the pick process, we improve the Gabor filter algorithm special condition and reduce the timecomplexity of the algorithm greatly. PMID- 17281447 TI - A method for accurate estimation of stimulating sites based on cerebral cortex structure in transcranial magnetic stimulation. AB - Transcranial magnetic stimulation (TMS) is a non-invasive and painless method to stimulate the cortex. Accurate estimation of stimulating points is much important to evaluate cortical functions such as cortical motor output maps. However, most studies using TMS have not achieved to estimate the stimulating points exactly. This study proposed the novel method to provide the accurate estimation of stimulating points of the cortex in TMS taking account of the individual cortical anatomy and property of nerve excitation. We conducted TMS mapping of the motor cortex to confirm the validity of this method. The cortex sites which innervate muscles of the upper limb and hand were successfully delineated in primary motor area. PMID- 17281448 TI - Comparison of fMRI BOLD Effect and Arterial Pulsation Harmonic Distribution among Different Breathing Rate. AB - The phenomenon of respiratory sinus arrhythmia (RSA) had been studied since 1733. Most researches were focused on the heart rates or blood pressure variability. It was well known that heart rate variability (HRV) induced by respiration decreased progressively with age. In general, it is caused by the function of the autonomic nervous system (ANS). Seldom researches studied the relationship of this phenomenon with cerebral circulation. In our previous research, we found that different breathing rate could redistribute the proportion of systemic circulation, and also observed that the slower the breathing rate the more proportion of cerebral circulation appeared on head. In this paper, we further examined the BOLD (Blood Oxygenation Level Dependent) signal fluctuations in brain stem among different breathing rate by the technique of functional magnetic resonance imaging (fMRI). We found that the BOLD signal changes were hinged on the breathing rate, and the variability was consistent with the pulsatile pressure study. PMID- 17281449 TI - Functional brain imaging by EEG graph-matching. AB - Our goal is to image the brain activation and function by the mean of electroencephalogram signals. The work's originality is that we build a data structure, a graph, that sums up the brain activity in the spatial, temporal and frequency domain. This graph is formed from the information included in the EEG time-frequency map. Contrary to methods trying to reproduce or analyze the whole complexity of the signal, our method is based on a multi-scale approach. In this order the level of information extraction could be adapted. So as to obtain a pattern of activation or to compare different EEG signals, we use some techniques of graph-matching on our data structure. The developed algorithm is based on the A* algorithm that allows us to compare variations of the recorded EEG answer in term of latency, frequency, energy and activated areas. The first results of this new project show on the one hand that the graph is a good choice to sums up the cortical activity and on the another hand that the graph-matching offers some interesting perspectives in order to describe the functional brain activity. PMID- 17281450 TI - Comparison of fMRI BOLD Effect and Arterial Pulsation Harmonic Distribution among Different Breathing Rate. AB - The phenomenon of respiratory sinus arrhythmia (RSA) had been studied since 1733. Most researches were focused on the heart rates or blood pressure variability. It was well known that heart rate variability (HRV) induced by respiration decreased progressively with age. In general, it is caused by the function of the autonomic nervous system (ANS). Seldom researches studied the relationship of this phenomenon with cerebral circulation. In our previous research, we found that different breathing rate could redistribute the proportion of systemic circulation, and also observed that the slower the breathing rate the more proportion of cerebral circulation appeared on head. In this paper, we further examined the BOLD (Blood Oxygenation Level Dependent) signal fluctuations in brain stem among different breathing rate by the technique of functional magnetic resonance imaging (fMRI). We found that the BOLD signal changes were hinged on the breathing rate, and the variability was consistent with the pulsatile pressure study. PMID- 17281451 TI - Studies of chinese original quiet sitting by using functional magnetic resonance imaging. AB - Since different meditations may activate different regions in brain, we can use functional magnetic resonance imaging (fMRI) to investigate it. Chinese original quiet sitting is mainly one kind of traditional Chinese meditation. It contains two different parts: a short period of keeping phrase and intake spiritual energy, and a long period of relaxation with no further action. In this paper, both those two stages were studied by fMRI. We performed two different paradigms and found the accurate positions in the brain. The pineal gland and the hypothalamus showed positive activation during the first and second stages of this meditation. The BOLD (Blood Oxygenation Level Dependent) signal changes had also been found. PMID- 17281452 TI - Effect of Contact Impedance on the Head Electrical Properties Based on EIT Technology. AB - Electrical impedance tomography (EIT) is a noninvasive technique that permits estimation of resistivity within a subject by reconstructing from boundary measurements. The head electrical properties based on EIT technology have been studied by many authors and in most of this work the realistic head model has been considered without contact impedance between the electrodes and the scalp. It is interesting to evaluate the effect of contact impedance on surface potential distributions because the contact impedance and the current density through this contact impedance are both high. In this paper we describe a complete electrode realistic head model that takes into account the presence of the electrode-scalp contact impedance. Using the finite element method (FEM), we get the surface potential distribution curves whose amplitude and shape are affected evidently by the magnitude of the contact impedance. The complete electrode realistic head model can be used to improve the precision of the reconstructed images by EIT. PMID- 17281453 TI - Repeated decompositions reveal the stability of infomax decomposition of fMRI data. AB - In this study, we decomposed 12 fMRI data sets from six subjects each 101 times using the infomax algorithm. The first decomposition was taken as a reference decomposition; the others were used to form a component matrix of 100 by 100 components. Equivalence relations between components in this matrix, defined as maximum spatial correlations to the components of the reference decomposition, were found by the Hungarian sorting method and used to form 100 equivalence classes for each data set. We then tested the reproducibility of the matched components in the equivalence classes using uncertainty measures based on component distributions, time courses, and ROC curves. Infomax ICA rarely failed to derive nearly the same components in different decompositions. Very few components per data set were poorly reproduced, even using vector angle uncertainty measures stricter than correlation and detection theory measures. PMID- 17281454 TI - Study of 99mTc-TRODAT-1 imaging on human brain with children autism by single photon emission computed tomography. AB - To evaluate the application values of99mTc-2 β [N, N′ , - bis (2-mercaptoethy1) ethylenediamino] methyl, 3 β -(4-chlorophenyl) tropane (TRODAT-1) dopamine transporter (DAT) SPECT imaging in children autism, and offer the academic foundation to etiology, mechanism and clinical therapy of autism. Ten autistic children and ten healthy controls were examined with 99mTc-TRODAT-1 DAT SPECT imaging. Striatal specific uptake of 99mTc-TRODAT-1 was calculated with region of interest analysis according to the ratios between striatum and cerebellum [(STR-BKG)/BKG]. There was no difference in semiquantitative dopamine transporter between bilateral striatum in autistic children (p=0.562) and in normal controls (p=0.573); Dopamine transporter in brain of patients with autism increased significantly than that in normal controls (p=0.017). Dopaminergic nervous system is dysfunction in human brain with children autism, and DAT 99mTc TRODAT-1 SPECT imaging on human brain will help the imaging diagnosis of children autism. PMID- 17281455 TI - Evaluating spatial normalization methods for the human brain. AB - Cortical mapping (CSM) studies have shown cortical locations for language function are highly variable from one subject to the next. If individual variation can be normalized, patterns of language organization may emerge that were heretofore hidden. In order to uncover these patterns, computer-aided spatial normalization to a common atlas is required. Our goal was to determine a methodology by which spatial normalization methods could be evaluated and compared. We developed key metrics to measure accuracy of a surface-based (Caret) and volume-based (SPM2) method. We specified that the optimal method would i) minimize variation as measured by spread reduction between CSM language sites across subjects while also ii) preserving anatomical localization of all CSM sites. Eleven subject's structural MR image sets and corresponding CSM site coordinates were registered to the colin27 human brain atlas using each method. Local analysis showed that mapping error rates were highest in morphological regions with the greatest difference between source and target. Also, SPM2 mapped significantly less type 2 errors. Although our experiment did not show statistically significant global differences between the methods, our methodology provided valuable insights into the pros and cons of each method. PMID- 17281456 TI - Enhancing feature extraction with sparse component analysis for brain-computer interface. AB - Feature extraction is very important to EEG-based brain computer interfaces (BCI) in helping achieve high classification accuracy. Preprocessing of EEG signals plays an important role, because an effective preprocessing method will help enhance the efficiency of the feature extraction. In this paper, sparse component analysis (SCA) is employed as a preprocessing method for EEG based BCI. A combined feature vector is constructed. This feature vector consists of a dynamical power feature and a dynamical common spatial pattern (CSP) feature. The dynamical power feature is extracted from selected SCA components, while the dynamical CSP feature is extracted from raw EEG data. Using the presented preprocessing and feature extraction method, we analyze the data for a cursor control BCI carried out at Wadsworth Center. Our results show that SCA preprocessing is the most effective in extracting a component which reflects the subject's intention, and demonstrate the validity of SCA preprocessing for the enhancement of feature extraction. PMID- 17281457 TI - Application of wavelet in speech processing of cochlear implant. AB - Cochlear Implant bypasses damaged hair cells and stimulates the auditory nerve directly in the cochlea. Wavelets are especially useful for speech processing of CI, since in the case of wavelets one speaks of a constant-Q filter bank as well as the cochlea. In this paper, a continuous wavelet has application in the filter bank design and an effective result is obtained. Also the lifting scheme, the so called second generation of wavelet, is adopted, combined with pitch extraction algorithm, to extract fundamental frequency of speech signal. Veracious result is obtained, which shows the great potential of wavelet an lifting scheme in the application in speech processing strategy for cochlear implants based on characteristics of Chinese language. PMID- 17281458 TI - An Improvement of Speech Synthesis in Acoustic Simulation Model of Cochlear Implants with CIS Strategy. AB - A cochlear implant is a new device to be implanted in the inner ear and restore partial hearing to profoundly deaf people. This article first presents the acoustic simulation principle based on CIS speech processing strategy, and then proposes an improved speech synthesis model of this acoustic simulation. Finally, on the basis of acoustic simulation experiments□results on normally hearing listeners, we get a close speech recognition to the result of implants patients, and suggest that our improvement be effective on evaluating cochlea processing strategies. PMID- 17281459 TI - Laboratory PC and Mobile Pocket PC Brain-Computer Interface Architectures. AB - EEG-based brain-computer interface (BCI) systems convert brain activity into control signals and have been developed for people with severe disabilities to improve their quality of life. A BCI system has to satisfy different demands depending on the application area. A laboratory PC based system allows the flexible design of multiple/single channel feature extraction, classification methods and experimental paradigms. The key advantage of a Pocket PC based BCI approach is its small dimension and battery supply. Hence a mobile BCI system e.g. mounted on a wheelchair can be realized. This study compares and discusses thoroughly the two mentioned approaches. PMID- 17281460 TI - A wireless EEG sensors system for computer assisted detection of alpha wave in sleep. AB - To gain good alpha wave for diagnosing insomnia in the situation which patient feeling comfort, an EEG sensor was designed with shorter electrode wires, battery supplied and wireless transmitter, whose another usage is brain-computer interface (BCI). The result of test represents the system can get good alpha wave and reject power-line interference at all. PMID- 17281461 TI - Investigation of the Type-2 Fuzzy Logic Approach to Classification in an EEG based Brain-Computer Interface. AB - Analysis of electroencephalogram (EEG) requires a framework that facilitates handling the uncertainties associated with the varying brain dynamics and the presence of noise. Recently, the type-2 fuzzy logic systems (T2 FLSs) have been found effective in modeling uncertain data. This paper examines the potential of the T2 FLS methodology in devising an EEG-based brain-computer interface (BCI). In particular, a T2 FLS has been designed to classify imaginary left and right hand movements based on time-frequency information extracted from the EEG with the short time Fourier transform (STFT). Robustness of the method has also been verified in the presence of additive noise. The performance of the classifier is quantified with the classification accuracy (CA). The T2 fuzzy classifier has been proven to outperform its type-1 (T1) counterpart on all data sets recorded from three subjects examined. It has also compared favorably to the well known classifier based on linear discriminant analysis (LDA). PMID- 17281462 TI - Enhancing Temporal Classification of AAR Parameters in EEG single-trial analysis for Brain-Computer Interfacing. AB - Adaptive autoregressive (AAR) coefficients provide dynamic spectral information in EEG single-trial analysis. In this paper we propose a temporal evidence accumulation framework to enhance classification of AAR features. The results for a single subject, using 280 trials, indicate distinct improvements over a conventional method of temporal classification. We illustrate how the framework is applicable to AAR features, as well as to wavelet features as reported in [13]. These findings put the two time-frequency features on equal footing for comparison in this context. PMID- 17281463 TI - Development of EEG biofeedback system based on virtual reality environment. AB - A noninvasive EEG biofeedback system based on virtual reality (VR) environment is developed. The system translates EEG signals into movement and interaction. VR environment provides an ideal medium to represent the spatial and temporal nature of electrical activity emanating from the brain. The VR environment is developed based on MS DirectX technique. SMR-component based biofeedback training in three normal male subjects and two female subjects are reported. The difficulties in biofeedback research and our future research interests are discussed. PMID- 17281464 TI - Comparison between Effective Features Used for the Bayesian and the SVM Classifiers in BCI. AB - Brain-computer interface (BCI) is based on processing signals recorded from the scalp, the surface of the cortex or from the inside of the brain in order to identify desired actions or behaviors. In BCI we are interested in extracting the most effective features from rare data in order to have the desired classification results. In this paper besides proposing two discrimination algorithms for classifying imagined movements of the left small finger and the tongue, a comparison has been done between the effective features applied by the Bayesian and the SVM classifiers for the BCI task. In fact the comparison was done on the most effective features found from a pool of extracted features for each classifier, separately. Finally using the most effective features of each classifier, the classification accuracy of 89.21% and 91.01% were achieved for the Bayesian and the SVM classifiers, respectively. PMID- 17281466 TI - Phase synchronization analysis and support vector machine for recognition of mental tasks. AB - A measuring method of phase synchronization is presented for analyzing event related electroencephalogram (EEG) recordings. The mean phase coherence (MPC) of EEG recordings during imagination of hand movement is calculated. Furthermore, the support vector machine is used for classification of the mental tasks. The preliminary results suggest that MPC could be promising method for brain-computer interfaces. Dynamic MPC measurement provides a new idea for recognition of mental tasks. PMID- 17281465 TI - Study on the effect of different frequency bands of EEG signals on mental tasks classification. AB - Currently, frequency bands not more than 40 Hz are usually used to perform mental tasks classification in brain-computer interface systems. In this study, by using Keirn's EEG data, we studied the effects of ten 10 Hz-wide subbands between 0 and 100 Hz on mental tasks classification. Features were computed in frequency domain as the sum of weighted power spectral value in each subband at each channel (C3, C4, P3, P4, O1, and O2). Fisher's linear discriminant was used to perform task pair classification. Our results indicated that subbands ranging from 30 to 100 Hz resulted in relatively greater classification accuracy at many scalp sites. The average classification accuracy of 98.3% across 130 task pairs was achieved by using features including those obtained on gamma bands (30-100 Hz), which is much greater than that of 89.3% by using the frequency band 0-30 Hz only. PMID- 17281467 TI - EEG recognition based on multiple types of information by using wavelet packet transform and neural networks. PMID- 17281468 TI - Design and implementation of High Performance Visual Stimulator for Brain Computer Interfaces. AB - An algorithm for implementing visual stimulators on generic computers has been developed for Brain Computer Interfaces (BCIs). It uses the hardware counter present in these systems to derive accurate timing. Simultaneous display of 20 patterns (e.g. 3×3 checkerboards) modulated at different frequencies is possible. The pattern used for stimulating the Steady State Visual Evoked Potential (SSVEP) can be changed with ease. The stimulators are evaluated using software counters. High accuracy (less than 0.73% error) and precision (0.1% coefficient of variation) is recorded for 20 patterns set with frequencies between 6 Hz and 15 Hz. PMID- 17281469 TI - A Wearable Home BCI system: preliminary results with SSVEP protocol. AB - This paper presents and discusses the realization and the performances of a wearable system for EEG-based BCI applications. The system (called Kimera) consists of a two-layer hardware architecture (the wireless acquisition and transmission board based on a Bluetooth ® ARM chip, and a low power miniaturized biosignal acquisition analog front end) together with a software suite (called Bellerophonte) for the Graphic User Interface management, protocol execution, data recording, transmission and processing. The implemented BCI system was based on the SSVEP protocol, applied to a two state selection by using standards display/monitor with a couple of high efficiency LEDs. The frequency features of the signal were computed and used in the intention detection. The BCI algorithm is based on a supervised classifier implemented through a multi-class Canonical Discriminant Analysis (CDA) with a continuous realtime feedback based on the mahalanobis distance parameter. Five healthy subjects participated in the first phase for a preliminary device validation. The obtained results are very interesting and promising, being lined out to the most recent performance reported in literature with a significant improvement both in system and in classification capabilities. The user-friendliness and low cost of the Kimera& Bellerophonte platform make it suitable for the development of home BCI applications. PMID- 17281470 TI - A statistical model of brain signals with application to brain-computer interface. AB - This paper presents a novel approach to improving the robustness of brain computer interfaces by using a statistical model of brain signals especially P300. We study the distributions of support vector machine scores for the signals and derive a posteriori probability model of P300/non-P300. We further derive a statistical model for multi-trial brain signals, and apply it to the rejection of undesired signals. Six subjects have been involved in an experimental study. The results demonstrate that the P300 model and the rejection method are appropriate and can help improve the robustness of the system significantly. PMID- 17281471 TI - Common Spatial Pattern Method for Channel Selelction in Motor Imagery Based Brain computer Interface. AB - A brain-computer interface(BCI) based on motor imagery (MI) translates the subject's motor intention into a control signal through classifying the electroencephalogram (EEG) patterns of different imagination tasks, e.g. hand and foot movements. Characteristic EEG spatial patterns make MI tasks substantially discriminable. Multi-channel EEGs are usually necessary for spatial pattern identification and therefore MI-based BCI is still in the stage of laboratory demonstration, to some extent, due to the need for constanly troublesome recording preparation. This paper presents a method for channel reduction in MI based BCI. Common spatial pattern (CSP) method was employed to analyze spatial patterns of imagined hand and foot movements. Significant channels were selelcted by searching the maximunms of spatial pattern vectors in scalp mappings. A classification algorithm was developed by means of combining linear discriminat analysis towards even-related desynchronization (ERD) and readiness potential (RP). The classification accuracies with four optimal channels were 93.45% and 91.88% for two subjects. PMID- 17281472 TI - Optimization of BCI Speller Based on P300 Potential. AB - We report our studies on a Brain Computer Interface (BCI) speller application with an aim to optimize its performance and usability. We study the dependence of the spelling accuracy as a function of (a) the number of visual stimuli (repetitions) presented to the user, (b) the P300 segment length used, (c) the number of channels used, and (d) the amount of data used in training, in terms of the number of characters and repetitions. Reducing the number of repetitions results in a direct reduction of the time needed to spell a character, while minimizing the number of channels translates to shorter subject preparation time and thus improves the usability of the system. The usability is further enhanced by decreasing the training required, while maintaining the accuarcy. We show that very high accuracies of the order of 99% can be achieved with a short training session of less than 10 minutes using only about 10 channels. The high accuracies, short training and preparation time requirements along with real-time performance make this BCI speller a viable communication tool for severely disabled individuals, who have no other means to communicate with the external world. PMID- 17281473 TI - P300 brain-computer interface design for communication and control applications. AB - This paper introduces the design of a P300-based brain-computer interface (BCI) system. Based on this system, two applications are implemented: a word speller and a remote control device, which are to assist physically disabled people to communicate and control. A number of specific implementation techniques are proposed to achieve good performance in terms of accuracy and reliability. The word speller can achieve a spelling rate of up to 4-6 letters per minute, while both applications achieve 99% accuracy in our experiments with healthy subjects. PMID- 17281474 TI - Classification of Wrist Movements using EEG-based Wavelets Features. AB - Our aim is to assess and evaluate signal processing and classification methods for extracting features from EEG signals that are useful in developing brain computer interfaces. In this paper, we report on results of developing a method to classify wrist movements using EEG signals recorded from a subject whilst controlling a joystick and moving it in different directions. Such method could be potentially useful in building brain-computer interfaces (BCIs) where a paralysed person could communicate with a wheelchair and steer it to the desired direction using only EEG signals. Our method is based on extracting salient spatio-temporal features from the EEG signals using continuous wavelet transform. We perform principal component analysis on these features as means to assess their usefulness for classification and to reduce the dimensionality of the problem. We use the results from the PCA as means to represent the different directions. We use a simple technique based on Euclidean distance to classify the data. The classification results show that we are able to discriminate between different directions using the selected features. PMID- 17281475 TI - Identification and Classification for finger movement based on EEG. AB - Identification and classification technology plays an important part in study of the BCI system. There are many algorithms to classify the event of different task related. Here, finger movement was used as the basic and typical tasks to be identified in the BCI experiments. The ideas of BP and ERD were introduced and discussed. The CSSD (common spatial subspace decomposition) algorithm was used for classifying single-trial EEG during the preparation of left-right finger movements after the two kinds of phenomena were expounded in detail in this paper. Experiment and simulating results show that the averaged classification accuracy can be up to the 75.6%. PMID- 17281476 TI - Improving signal separability and inter-session stability for a brain-computer interface by time-series-prediction-preprocessing. AB - This paper presents a preprocessing procedure for improving the separability of electroencephalogram (EEG) signals recorded from subjects for a right/left motor imagery based brain-computer interface (BCI). The EEG data is preprocessed utilizing a recently proposed time-series-prediction (TSP) technique. Two neural networks (NNs) are trained to perform one-step-ahead predictions of the EEG time series data where one NN is trained to predict right motor imagery signals and the other left motor imagery signals. The NNs are used in a procedure referred to as neural-time-series-prediction-preprocessing (NTSPP) where signals are fed into both NNs and two new signal types are produced i.e. the predicted signals (Ys) or the prediction error signals (Es). In this investigation the well known adaptive autoregressive modeling (AAR) technique is used to extract features from the Es and Ys signals. Classification is performed using linear discriminant analysis (LDA). This NTSPP procedure is tested offline on three subjects and classification accuracy (CA) rates approach 98%. The approach shows significant potential for improving robustness and feature stability across sessions and a clearly distinguishable improvement in performance is observed when features are extracted from the NTSPP signals compared to those extracted from the original signals (Os). PMID- 17281477 TI - Application of t1 and t2 maps for stereotactic deep-brain neurosurgery planning. AB - This work presents the application of a quantitative magnetic resonance imaging (MRI) technique in stereotactic deep-brain neurosurgery planning procedures. The high spatial resolution T1and T2maps acquired using this imaging method have been normalized to the standard CJH-27 brain coordinate system and integrated into a neurosurgical visualization and navigation system to improve the accuracy of surgical target localization. The T1and T2maps, along with the standardized anatomical and functional information within this system, can be navigated, non-rigidly registered, and arbitrarily processed. Once applied to individual patients, these maps facilitate the delineation of surgical targets. Our preliminary studies compared the centroids of segmented deep-brain nuclei based on the T1and T2maps with those according to Schaltenbrand and Wahren atlas, and with the actual surgical targets of 15 patients who had undergone thalamotomy, pallidotomy, and subthalamic nucleus deep-brain stimulation. The average displacement was 3.21mm±0.80mm, indicating the potential capability of this system to accurately initiate target identifications. PMID- 17281478 TI - Distinguishing Between Left and Right Finger Movement from EEG using SVM. AB - A hybrid BSS-SVM method for distinguishing between left and right finger movements from the electroencephalogram (EEG) has been developed. Support vector machines (SVM) is used to effectively classify the extracted features incorporating blind source separation (BSS) and directed transfer functions (DTF). This is the basis for a brain computer interface (BCI). We analyzed 200 trials of 64 electrode EEG data from which we trained the classifier and tested our system. We demonstrated that by classification of such appropriate features we can reliably distinguish between left and right finger movements. PMID- 17281479 TI - Portable active surface laplacian EEG sensor for real-time mu rhythms detection. AB - A novel active surface Laplacian electroencephalogram (LEEG) sensor for the real time mu rhythms detection has been developed in our study. Analog LEEG signals with high signal to noise ratio obtained directly by using the active sensor can reduce the duration and quantum error of digital signal processing and computation for the quick and precise control of brain-computer interface (BCI) systems. The portable active surface LEEG sensor comprises five gold electrodes integrated to a cross-shaped structure and a battery-powered, low-noise amplifier with the following specification: gain of 10,000, band-pass filtering from 2.5 Hz to 55 Hz, input impedance of 10 GΩ, common mode rejection ratio (CMRR) of 110 dB. The clinical experiments showed that the amplitude suppression of mu waves detected directly by active surface LEEG sensors was obvious as the normal subject was asked to imagine grasping something with his right hand. Furthermore, the distribution of mu waves captured real time in the un-shielded room by active surface LEEG sensor was similar to that acquired in the shielded room of hospital through EEG data collection by an EEG instrument, and then offline analyses. Real time mu rhythms obtained by the active surface LEEG sensor will be utilized to control a device or system via the BCI in real time. PMID- 17281480 TI - Variations in Anterior-Posterior CoP Patterns in Elderly Adults Between Psychophysically Detected and Non-Detected Short Horizontal Perturbations. AB - Using an ultra-low-vibration Sliding Linear Investigative Platform for Assessing Lower Limb Stability (SLIP-FALLS), postural responses were evaluated while subjects stood on a platform that was given a short anterior perturbation presented in one of 2 sequential test intervals for a set of 30 trials. An adaptive 2-Alternative-Forced-Choice protocol required the subject to detect platform movement. Anterior-Posterior Centers-of-Pressure (AP CoP) were compared among the detected and non-detected trials for the Healthy Elderly Adults (HEA) and Diabetic Peripheral Neuropathy (DPN) elderly adults. Results indicate that there is a significant difference between the CoP patterns for a detected and non detected trial. Also, the range of sway is found to be higher in the case of DPN elderly adults when compared to HEA. However, the AP CoP pattern for detected trials in both HEA and DPN were the same. PMID- 17281481 TI - Unobtrusive computer monitoring of sensory-motor function. AB - Cognitive assessments and the early detection of dementia are an important component of clinical care. In this paper we describe an approach to continuous monitoring of sensory-motor function that corresponds to standard tests of cognitive function, but measured more frequently and in a natural home environment. The approach is based on monitoring human-computer interactions using standard devices such as keyboard and pointing devices. PMID- 17281482 TI - Evidence for schema theory from surface electromyography: an artificial neural network approach. AB - In order to study voluntary movement control, we applied artificial neural networks (ANNs) to define the temporal patterns of surface electromyography (SEMG) activity used by normal subjects in performing three tasks, namely, wrist extension, continuous extension-flexion movements and extension-flexion movements for which the pause time between extension and flexion were 250 ms. SEMGs of 8 muscles were simultaneously recorded together with wrist movement. The results provided some evidence for the schema theory. PMID- 17281483 TI - Prediction of Driving Ability in Persons with Brain Disorders using Sensory-Motor and Cognitive Tests. AB - Brain lesions and degeneration can lead to a decreased ability to perform the physical and cognitive functions necessary for safe driving. A battery of computerized sensory-motor and cognitive tests (SMCTests™) has been developed to quantify sensory-motor and cognitive dysfunction, with particular application to the assessment of driving abilities in patients with neurological disorders. SMCTests and an on-road driving assessment were applied to 50 subjects with brain lesions referred to the Driving and Vehicle Assessment Service at Burwood Hospital, Christchurch (36 males, 14 females; age range 43-85 years, mean age 71.3 years; 35 stroke, 4 traumatic brain injury, 4 Alzheimer's disease, 7 with other diagnoses). Two techniques were used to build model equations for prediction of on-road driving ability based on SMCTests performance - binary logistic regression and nonlinear causal resource analysis (NCRA). Binary logistic regression correctly classified 94% of referrals as on-road pass or fail, while NCRA correctly classified 90% of referrals. Leave-one-out cross validation analysis estimated that binary logistic regression would correctly predict the classification of 86% of an independent referral group as on-road pass or fail, while NCRA would correctly predict 76%. Results indicate that the predictive model based on binary logistic regression would be slightly more accurate than NCRA at predicting on-road pass or fail in an independent subject group. Conversely, the NCRA model also provides valuable information on the extent to which a subject would pass or fail an on-road driving assessment and identifies the deficit which most limits their driving ability. PMID- 17281484 TI - On the interest of computer modelling in the validation of ambulatory measurement of movement disorders in man. AB - Continuous ambulatory monitoring is a promising technique for objective evaluation of movement disorders in man. Although technological progress make such devices currently available, no validated measurements exist. We propose an original approach to validate instrumental measurements in central neurological diseases, based upon the use of computer modeling of movement disorders. In such an approach, computer simulations of altered movement were used to validate accelerometric-derived measurements in spasticity and Parkinson's disease. We found that some measurements, derived from the frequency power spectrum of distal acceleration at the upper limb, may be suitable for evaluation of some motor disorders, as spasticity, parkinsonian rigidity and related motor disability. Direct applications are expected in ambulatory monitoring of neurological diseases. PMID- 17281485 TI - Effects of deep brain stimulation on adaptive control of reaching. AB - Lesion or degeneration of the cerebellum can profoundly impair adaptive control of reaching in humans. Computational models have proposed that internal models for motor action form in the cerebellum and influence planned motor output through the cerebello-thalamo-cortical pathway. However, lesions in the cerebellar thalamus have not been consistently shown to result in motor adaptation impairment. To elucidate the role of the cerebellar thalamus in humans, we studied a group of essential tremor (ET) patients with deep brain stimulation (DBS) electrodes placed in the cerebellar thalamus. The stimulation can be turned on or off remotely, and is thought to reduce tremor by blocking the spread of the pathological output from the cerebellum. We found that while thalamic DBS resulted in a dramatic reduction in ET, it also led to impaired motor adaptation in the patients. Thus, human adaptive reaching motor control depends on the integrity of the thalamic nucleus that relays cerebellar output to the cerebral cortex. PMID- 17281486 TI - Spectral analysis for diagnosis of rectum cancer using fluorescence and Raman spectroscopy of serum. AB - Laser-induced fluorescence spectroscopy (LIF) and Raman spectrum of serum for diagnosis of rectum cancer were investigated by criteria of three parametric modes in this paper. The aim of this study was in an attempt to find the difference normal and rectum cancer cases, therefore 89 rectum cancer samples were measured using fluorescence and Raman spectrum. The experimental result showed that there were three obvious Raman peaks of normal case, and no Raman peak or only slight Raman peak of rectum cancer serum. Ratio of Raman peak relative intensity and fluorescence peak red shift both different. Additionally, ratio of fluorescence peak relative intensity is different at start position and end position also. And obtained 80.7% accuracy to rectum cancer compared to clinical diagnostic. It is exploring that use Raman spectrum and LIF to detection of cancer. PMID- 17281487 TI - Study of method and system for diagnosis of cancer using autofluorescence and Raman spectroscopy. AB - induced fluorescence(LIF) and Raman spectra were measured from normal and tumorous human serum in an attempt to discover some values useful in discrimination between normal and tumorous cases. Red shift of fluorescence peak and decrease of fluorescence intensity were observed after samples radiated by laser. According to one thousand twenty-two samples' spectra, three parameters α, β and δγ are introduced to distinguish normal, benign and malignant from one another. The application of such parameters in clinical diagnosis was researched. The practical instrument of laser-induced serum fluorescence and resonance Raman spectra for cancer diagnosis or incipient cancer is designed, by combining laser spectroscopy, biomedical, photo-electron technology, controlling technology and computer technology. The instrument is intelligent for operating and diagnosing. The clinic application of this instrument has been carried out successfully in the diagnosing of stomach cancer and liver cancer (459 cases); the accuracy is about 85%. It develops a new technology in the field of cancer diagnosis. PMID- 17281488 TI - Advanced radiology information system. AB - The innovative features of an advanced Radiology Information System (RIS) are presented in this paper. The interoperability of RIS with the other Intra hospital Information Systems that interacts with, dealing with the compatibility and open architecture issues, are accomplished by two novel mechanisms [1]. The first one is the particular message handling system that is applied for the exchange of information, according to the Health Level Seven (HL7) protocol's specifications and serves the transfer of medical and administrative data among the RIS applications and data store unit. The same mechanism allows the secure and HL7-compatible interactions with the Hospital Information System (HIS) too. The second one implements the translation of information between the formats that HL7 and Digital Imaging and Communication in Medicine (DICOM) protocols specify, providing the communication between RIS and Picture and Archive Communication System (PACS). The whole structure ensures the automation of the every-day procedures that the ;medical protocol' specifies and provides its services through a friendly and easy to manage graphical user interface. PMID- 17281489 TI - An integrated system for the support of an emergency health care department. AB - In this paper, we present the design and development of an integrated database system for the support of an emergency health care department. The system allows patient administration, patient record management, information exchange within the department and Ambulance vehicles management. It was designed as an addition to a previous developed system which supports emergency telemedicine. The system has passed the initial testing and verification phase and is now entering the final evaluation phase before moving into the department's daily routine. PMID- 17281490 TI - Health-Mining: a Disease Management Support Service based on Data Mining and Rule Extraction. AB - The disease management is the collection of the processes aimed to control the health care and improving the quality at same time reducing the overall cost of the procedures. Our system, Health-Mining, is a Decision Support System with the objective of controlling the adequacy of hospitalization and therapies, determining the effective use of standard guidelines and eventually identifying better ones emerged from the medical practice (Evidence Based Medicine). In realizing the system, we have the aim of creation of a path to admissions- appropriateness criteria construction, valid at an international level. A main goal of the project is rule extraction and the identification of the rules adequate in term of efficacy, quality and cost reduction, especially in the view of fast changing technologies and medicines. We tested Health-Mining in a real test case for an Italian Region, Regione Veneto, on the installation of pacemaker and ICD. PMID- 17281491 TI - Communication and storage of digital medical images in database. AB - This paper presents the development of an application for communication and storage of clinical images based upon the Digital Imaging and Communications in Medicine (DICOM) protocol. The proposed solution is composed of three different databases servers, PostgreSQL, Firebird and Oracle, and a DICOM client software, that uses the protocol TCP/IP. It provides the communication services, transmission, storage and administration of medical images. PMID- 17281492 TI - Intelligent patient and nurse scheduling in ambulatory health care centers. AB - Ambulatory health care centers are the major arena for delivery of primary health care to patients. In contrast to hospital or urgent care scheduling systems, ambulatory health care centers offer different challenge for scheduling optimization. The aim is similar, i.e. to reduce the average waiting time and maintain high resource utilization, but the concept is different. In this paper we present a multi-agent based system for long-term scheduling, where agents use their time-series forecasting and pattern recognition abilities to predict possible patient flow peaks and inform the main scheduling agent of these events. To ease such peaks, we use adaptive nurse scheduling by adapting the nurse schedules each week-end. Our multi-agent system helps the personnel managers and other staff in health centers to adapt the nurse and patient scheduling in dependence of the current patient flow. PMID- 17281493 TI - Feature Extraction from Phonocardiogram for Diagnosis based on Expert System. AB - This paper describes a method for extracting features from a phonocardiogram to be used by an expert system for diagnostic purposes. The key issue is to choose features which match with the doctor's (expert's) diagnostic approach. Only in that way can the knowledge of the expert be effectively coded into rules within an expert system. PMID- 17281494 TI - Noninvasive measurement and evaluation of arterial stiffness. AB - For the purpose of measurement and evaluation of arterial stiffness, we design a noninvasive medical device based on the oscillometric method and the pulse wave velocity (PWV) method, and employ arterial stiffness index (ASI) and PWV as accessing parameters. The inner pressure signal of cuff on the upper arm and the pulse wave signal at the tip of finger will be sampled, and the special software can utilize these signals to calculate two accessing parameters and obtain the evaluation conclusion of arterial stiffness. The clinical experiments show that this medical device and evaluation method are effective and valuable. PMID- 17281495 TI - A simple Computational Model-Based Validation of Guyton's closed circuit analysis of the heart and the peripheral circulatory system. AB - A computer model of the human cardiovascular system has been created based on Guyton's closed circuit analysis of the heart and the peripheral circulatory system. This model was checked against Guyton's experiments performed in anesthetised dogs regarding the normal venous return curve, the effect of mean circulatory filling pressure (MCFP) and the importance of arterial venous and capillary resistance. These comparisons indicate that this simple model is valid for the study of Guyton's experimental work and also forms the bases of a more complex model of the cardiovascular model with specific attention to the venous system. PMID- 17281496 TI - A simple cycle-averaged model for cardiovascular dynamics. AB - Lumped-parameter time-varying electrical circuit analogs for cardiovascular systems are frequently used in computational models for simulating and analyzing hemodynamics. These pulsatile models provide details of the beat-by-beat or intracycle dynamics. In other settings, however, such as when tracking a hospital patient's hemodynamic state over time, it is more useful to track trends in the intercycle dynamics. In this paper, we apply a cycle-averaging method to a simple pulsatile cardiovascular model to derive a cycle-averaged model for cardiovascular dynamics. The resulting cycle-averaged model captures the intercycle dynamics with relatively small approximation errors for a large range of perturbations in parameters such as systemic vascular resistance. PMID- 17281497 TI - Monitoring Carotid Blood Flow and ECG for Cardiovascular Disease in Elder Subjects. AB - This report is to investigate the correlation between common carotid blood flow (CCBF) properties and the risk factors for cardiovascular disease. The measurement system was designed for simultaneously monitoring of CCBF and electrocardiogram (ECG) in order to get more valid information for detection and diagnosis of cardiovascular disease. In our study, blood flow velocimeter was developed to measure blood flow in carotid by using ultrasound Doppler technique. This measurement system is based on a continuous-wave (CW) Doppler ultrasound method with two semicircular piezoelectric (PZT) transducers, one continuously transmitting ultrasound, and the other continuously receiving the echoes. Eleven patients with cardiovascular disease underwent in the experiment. In the report, blood flow was compared with data from 25 healthy subjects which asymptomatic subjects putatively free of cardiovascular disease as controls. The maximum of CCBF velocity was 102.8 (SD 18.3) cm/s in the 25 healthy subjects. While, the maximum of CCBF velocities were 53.9 (SD 16.6) cm/s in the eleven cardiac patients. The data suggest that CCBF velocity decreased significantly in the cardiac patients and by simultaneously monitoring of CCBF and ECG were probably obtained more valid information to detect and diagnose cardiovascular disease at the early stage. PMID- 17281499 TI - Cancellation of respiratory artifact in impedance cardiography. AB - Impedance cardiography is a noninvasive technique for monitoring stroke volume, based on sensing variation in the thoracic impedance, z(t), due to blood flow. In this technique, first derivative of impedance, dz/dt, is used to calculate two parameters: ventricular ejection time and (-dz/dt)max.Respiration and motion artifacts cause base line drift in the sensed impedance waveform, mainly during exercise, and this drift results in errors in the estimation of the two parameters. Ensemble averaging of z(t) signal suppresses motion artifacts but it introduces distortion in the signal. In this study, simultaneously acquired respiratory signal is used for cancellation of corrupting respiratory artifact from the recorded z(t) signal, using adaptive noise cancellation technique. PMID- 17281498 TI - A 3D Static Heart Model From a MSCT Data Set. AB - Dynamic Computed Tomography (CT) imaging aims to access the kinetics of the moving organs. In cardiac imaging, the interest lies in the possibility of obtaining anatomic and functional information on the heart and the coronaries during the same examination. However, segmentation, reconstruction and registration algorithms need to be developed for diagnostic purposes. We propose thus to built a 3D heart model from Multi-slice Spiral Computed Tomography (MSCT) dynamic sequences to facilitate the evaluation of these algorithms. The model building relies on semi-automatic segmentation techniques based on deformable models such as Fast Marching and active contours. Shape-based interpolation and Marching Cube algorithms are then used for the 3D surface reconstruction. PMID- 17281500 TI - Arterial stiffness estimation in hypertension. AB - Arterial stiffness can be estimated noninvasively with various methods. Pulse pressure (PP), pulse wave velocity (PWV), stiffness index (SI), stroke volume (SV)/PP, proximal compliance (C1) and distal compliance (C2) are reported to be associated with arterial stiffness and can be used as predictors of cardiovascular events. 452 subjects were involved in the present study, mentioned six indices were obtained and compared to verify if they are suitable for the arterial stiffness estimation and which one is the most sensitive marker of arterial stiffness in hypertension. It is found that PWV has a good correlation with PP, SI and C2, and it is an effective index to distinguish hypertensive from normotensive. The receiver operating characteristic (ROC) analysis also evidenced the good performance of PWV in the diagnosis of hypertension. It is concluded that PWV is superior to other indices in reliably predicting arterial stiffness in hypertensive... PMID- 17281501 TI - Strong Coupling System for the LV Motion Simulation in a Distributed Simulation Environment. AB - A system where model parts can be easily exchanged and modified is of great advantage, especially in a combination of models such as an electrophysiological cell model and a mechanical model to a more complex left ventricular (LV) motion model. The use of a distributed simulation environment is straightforward because each simulation model is calculated by an existing user-friendly simulator. However, the weak coupling calculation usually used in a distributed environment reduces the accuracy of the simulation and results in an unstable simulation of the LV motion. To overcome this problem, we have developed a strong coupling simulation system for the distributed simulation environment. Simulation results for a myocardial tissue and a simple LV shape model are presented to elucidate the effectiveness of our system. PMID- 17281502 TI - Implantable blood flow measurement techniques for humans. AB - A wide range of blood flow measurement techniques were reviewed in regard to development of an implantable blood flow sensor. These include indicator methods and techniques to measure velocity and stroke volume. Most techniques were found to be unsuitable for implantable use in humans. The intracardiac impedance method was favored, though significant methodological obstacles remain. PMID- 17281503 TI - First heart sound detection for phonocardiogram segmentation. AB - This paper presents an algorithm for accurate and improved detection of the first heart sound S1for heart sound cardiac cycle segmentation under noisy environments. The proposed algorithm integrates an S1/S2selection step and an S1identification step. An adaptive sub-level tracking algorithm based on wavelet transform is proposed to separate the S1and S2from other components such as murmurs and noises. This is followed by a detection procedure based on Shannon energy to reject the overlapping interference so that the peaks of S1and S2can be detected. Criteria of time interval, energy and phonocardiogram (PCG) collecting position are used to identify S1with respect to the beginning of each cardiac cycle. Experimental results show that the proposed algorithm leads to an efficient segmentation of PCG cycle. Due to its simplicity and fast implementation, the method can be deployed clinically for further analysis and eventual use. PMID- 17281504 TI - Using neural network to recognize human emotions from heart rate variability and skin resistance. AB - The purpose of this paper is to estimate emotions using Neural network and the changes in activities of autonomic nervous system(ANS). Since ANS cannot be controlled artificially, we presumed that the changes in emotions would be reflected to the changes in ANS. In order to observe those changes, we provided the subjects with some video clips which can induce a variety of emotions and measured the changes in ANS, especially in Heart Rate Variability(HRV) and in Galvanic Skin Response(GSR). With those analyzed results from the experiments, we established an algorithm based on Neural network, finally we could reach the estimating rate of 80.2% PMID- 17281505 TI - Physiological and behavioral evaluation of mental load in shared attention tasks. AB - Hand-held phone use is prohibited by French law to prevent any motor interference with driving. If free-hands kit remains tolerated, its true impact (cognitive interference) is not already clearly determined. This experiment was aimed to study the effect of three communication tasks on driver's behavior: listening to the radio, discussing with a passenger and holding a hands-free phone conversation. Performance was assessed through reaction time (RT) to visual stimuli when driving on a private closed circuit. Drivers were requested to leave their foot from the accelerator pedal when orange lights, placed on the dashboard, switched on. This stimulus was triggered while subjects performed both driving and one of the three additional tasks. Skin resistance level (SRL) and instantaneous heart rate (IHR) were continuously recorded as indices of arousal. Rest and driving were taken as reference. Phoning while driving elicited the highest RT. SRL showed 3 levels of arousal, from the lowest to the highest: rest, driving and the dual task condition (driving + communication). Thus, arousal remained constant whatever the additional task although IHR showed that arousal was higher when phoning than when listening to the radio. Thus, managing two tasks simultanously elicited an increase in subjects' arousal whereas RT increased selectively as a function of the secondary task requirements. PMID- 17281506 TI - The Influence of Stochastic Organ Conductivity in 2D ECG Forward Modeling: A Stochastic Finite Element Study. AB - Quantification of the sensitivity of the electro-cardiographic forward problem to various parameters can effectively direct the generalization of patient specific models without significant loss in accuracy. To this purpose we applied polynomial chaos based stochastic finite elements to assess the effect of variations in the distributions of tissue conductivity in a two-dimensional torso geometry generated from MRI scans and epicardial boundary conditions specified by intra-operatively recorded heart potentials. The polynomial chaos methodology allows sensitivity analysis of this type to be done in a fraction of the time required for a Monte Carlo analysis. PMID- 17281507 TI - Using independent component analysis to research heart rate variability. AB - Independent component analysis (ICA) and neural networks were used to extract sub signals of heart rate variability (HRV). Electrocardiogram (ECG) recording was consisted of six minutes when the volunteer was lying and another six minutes when the volunteer was standing. HRV was extracted from ECG. According to time delay, HRV was divided into five groups as mixed signals. ICA and neural networks reconstructed five signals into two groups. Results showed that one group signal component centralized in low frequency (called IC1); the other did in high frequency (called IC2). The power of IC1 was significantly increased (P<0.05) and the ratio of IC1 to total power was significantly increased (P<0.01) from lying to standing. Comparing the two postural results, it shows that IC1 may express sympathetic activity, and IC2 represents parasympathetic activity. Sympathetic and parasympathetic nervous function can be evaluated respectively and quantificationally by data and graphs from the two decomposed components. Key word: Neural networks, Independent component analysis, Heart rate variability, Autonomic nervous system. PMID- 17281508 TI - Adaptive PI Regulation of Blood Pressure of Hypertension patients. AB - This paper presents an adaptive PI control of mean blood pressure using vasoactive drugs like SNP. A new algorithm updating variations in time delay and sensitivity of the system is proposed and its effectiveness is discussed. For demonstration, simulations under clinical conditions are carried out and the results show that the adaptive control system can effectively handle the changes in patient's dynamics and provide satisfactory performance in regulation of blood pressure of hypertension patients. PMID- 17281509 TI - Correlation Changes of EEG and ECG After Fast Cable CAR Ascents. AB - In the Eastern Alps in Europe, the Dachstein. massif with a height of almost 3000 m is an ideal location for investigating the effects of changes in altitude on the human body. Within a few minutes, a cable car facilitates an ascent from 1702 m to 2700 m above sea level, where the partial pressure of oxygen is about 550 mmHg (as compared to 760 mmHg at sea level). In this study ten healthy subjects performed a reaction time task at 990 m and 2700 m in altitude. The subjects were instructed to perform a right hand index finger movement as fast as possible after a green light flashed (repeated 50 times). The corresponding electrocardiogram (ECG) and the electroencephalogram (EEG) were recorded. From the ECG heart rate and heart rate variability measures in the time and frequency domain were calculated. An event-related desynchronization/synchronization (ERD/ERS) analysis was performed with the EEG data. Finally, the EEG activity and the ECG parameters were correlated. PMID- 17281510 TI - Influence of exposure to diesel emissions in rats and distribution profile for R R interval. AB - In order to evaluate the influence of diesel emissions on cardiac function we extracted resting R-R interval and a body activity index derived on a distribution profile of R-R interval. After seven months of exposure in rats revealed that particulate matter in diesel emissions decreases resting R-R interval and activity. PMID- 17281511 TI - Dynamic analysis of heart rate variability based on orthogonal wavelet transform. AB - The analysis of heart rate variability (HRV) has become a tool for noninvasively detecting the cardiovascular modulation of autonomic nervous system (ANS). Traditional analysis in frequency-domain mainly includes calculating the power and the peak frequency of each physiological frequency component. Whether employing the non-parametric or parametric method to estimate the power spectrum density (PSD), the approximate stationarity of HRV is presupposed. However, only in short-term analysis can data meet this condition. With the increase of the record time, the nonstationarity of HRV notably appears. A dynamic analysis method based on orthogonal wavelet transform was proposed in this paper, which not only can obtain the traditional indices in frequency-domain, but can compute their dynamic values varying with time, called short-time power and short-time LF/HF ratio. The latter can evaluate the activity of autonomic nervous system. Finally the method was applied to trace the balance of ANS in Atropin drug experiment. PMID- 17281512 TI - Dynamic analysis for blood flow parameters of cardiovascular system on work load. AB - In order to study the dynamic mechanism of blood flow parameters of cardiovascular system on work load, a dynamic mathematical model which can be used to describe quantitatively blood flow parameters of human body on different work load is put forward in this paper. With the help of this model, the correlation of blood flow parameters is studied using the analytic method of function of multiple variables. The experimental results are consistent with the analytic results of dynamic model. PMID- 17281513 TI - Fetal heart rate deceleration detection from the discrete cosine transform spectrum. AB - Automated detection of decelerations in fetal heart rate (FHR) signals can be posed as a problem of signal detection in the presence of noise. We present an algorithm that adaptively selects the resolution of analysis and uses the discrete cosine transform (DCT) to describe the spectrum at short-term and longer term scales. In so doing we generate near-orthogonal and scale-invariant features that are presented to a feedforward neural network for classification. PMID- 17281514 TI - Assessing Cardiovascular Function Status with Non-linear Indexes from HRV of Exercise Testing. AB - The purpose of this paper is to study the method to assess function status of cardiovascular system effectively in order to guide prevention and protection. In this study an exercise testing was performed in two groups. 60 elder hypertensives were chosen as a group at relative worse healthy status, and 60 young healthy subjects were chosen as a group at relative good healthy status. By discrete wavelet transform (DWT), exercise heart rate variability (EHRV) was obtained from the primary ECG recorded in exercise testing. Five groups of non linear indexes in pre exercise stage (PES), after exercise stage (AES) and whole stage (WS) were extracted from EHRV, respectively. They were appropriate entropy, relative complexity, and other three parameters extracted from Poincare dispersed dot Plot. Discriminant analysis was used to classify two testing groups. Statistical analysis indicates that nine indexes were significantly different between these two groups. A discriminant formula was used to classify the two groups and the classification rate was up to 85%. PMID- 17281515 TI - Effect of Novel Nanoscale Energy Patches on Spectral and Nonlinear Dynamic Features of Heart Rate Variability Signals in Healthy Individuals during Rest and Exercise. AB - LifeWave energy patches are novel nanoscale semiconducting biomolecular antennas, that when placed in the oscillating bioelectromagnetic field of the body, resonate at frequencies in unison with certain biomolecules in the cells and signal specific metabolic pathways to accelerate fat metabolism. As a consequence of accelerated fat burning more cellular energy becomes readily available to support all bodily energy-consuming functions. Heart rate variability refers to the beat-to-beat variation in heart rate (HR) and is modulated largely by the autonomic nervous system via changes in the balance between parasympathetic and sympathetic influences. Since short-term variations in HR reflect sympathetic nervous activity, they provide useful non-invasive markers for assessing autonomic control under various physiologic states and conditions. To evaluate the effect of LifeWave energy patches on HRV signals, pilot data from healthy volunteers were collected under three different conditions during rest and exercise using a BIOPAC system. The HRV signal was derived from preprocessed ECG signals using an Enhanced Hilbert Transform (EHT) algorithm with built-in missing beat detection capability for reliable QRS detection. Autoregressive (AR) modeling of the HRV signal power spectrum was achieved and different parameters from power spectrum as well as approximate entropy were calculated for comparison. Poincare plots were then used as a visualization tool to highlight the variations in HRV signals before and after exercise under normal conditions and under the influence of placebo and energy patches. PMID- 17281516 TI - Extraction of photoplethysmographic waveform variability by lowpass filtering. AB - Cardiovascular variability is known to provide useful physiological information about autonomic function and peripheral vascular tone. Previous studies have used systolic values (peaks) or diastolic values (troughs) in the photoplethysmographic signal (PPG) to represent the variability in the finger pulse waveform. However, the feature detection process is error prone and often requires manual correction which is time consuming. The current study has proposed the lowpass filtering method as an alternative means to extract the variability signal. The similarities between the lowpass filtered spectrum and the spectra produced by other representation methods were assessed quantitatively via the computation of normalized cross-correlations. Results showed that the lowpass filtered signal produced a variability spectrum which was nearly identical to that of the pulse waveform mean value (correlation = 0.996), and was highly correlated with the trough and the peak variability spectra (correlation > 0.9). Compared with feature extraction methods, the lowpass filtering method is much simpler and computationally efficient to implement. In addition, the lowpass filtering method can be applied in conjunction with signal decomposition techniques such as principal component analysis (PCA) to better quantify sympathetic change. PMID- 17281517 TI - Evaluation of the effect of visual stimulation on humans by simultaneous experiment with multiple subjects. AB - To evaluate the biological effects of visual stimulation on multiple subjects watching a same image, a more compact and low-cost device measuring both ECG and photo-plethysmogram was developed. On the basis of these physiological parameters, the maximum cross-correlation coefficient, ρmax, from pulse wave transmission time to heart rate could be calculated. This index reflects the activity of the autonomic nervous system and is considered as a good index for evaluating the effect of visual stimulation on humans. The result of simultaneous experiment with 6 subjects watching a video image taken by an intentionally swaying handy camera has shown that ρmaxof almost all subjects decreased in the latter part of the video image and that ρmaxof the subjects who felt motion sickness strongly decreased after watching the video image at a time. PMID- 17281518 TI - The Effects of Exercises on the Relationship between Pulse Transit Time and Arterial Blood Pressure. AB - Pulse transit time (PTT) is one of the physiological parameters that can be utilized to estimate arterial blood pressure (BP) non-invasively. However, the effects of successive exercises on the relationship between PTT and BP have not yet been studied systematically. This study examines the variation in PTT and BP on 15 healthy subjects after treadmill exercise. PTT-peak and PTT-foot, which represent the time intervals from the R-wave of electrocardiogram (ECG) to the peak and the foot of photoplethysmographic (PPG) signal, are verified respectively. ECG, PPG signal, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded from each subject. Experiment was divided into Pre exercise, Post-exercisel, Post-exercise2, and Recovery. Treadmill exercise was carried out before Post-exersie1 and Post-exercise2. It was found that SBP and DBP increased significantly while PTT-foot and PTT-peak decreased significantly immediately after exercises. During the phase of the Recovery, increment of PTT foot and hypotension phenomenon was temporarily observed. Throughout the experiments, PTT-foot and BP were inversely related under the effect of two successive exercises. Therefore, it is possible to estimate BP based on the PTT approach after successive exercises. PMID- 17281519 TI - Beat to beat classification of long electrocardiograms using entropies and hierarchical clustering. AB - This paper introduces an entropy based method for beat to beat classification of long electrocardiograms (ECGs). A state vector is reconstructed using Taken's delay coordinates method and Shannon entropies are calculated for each beat to form feature vectors. Hierarchical clustering is applied to these vectors to classify the beats. The algorithm was used for detection of atrial premature beats and ventricular premature beats in long electrocardiograms. PMID- 17281520 TI - Cardiac Beat Classification using a Fuzzy Inference System. AB - This paper presents an adaptive-network-based fuzzy inference system (ANFIS) as a cardiac beat detector, able to classify normal vs. premature ventricular contractions. We used records from the MIT Arrhythmia Database and in-vivo records from cardiac voluntary patients to train and test our system. The system identifies premature ventricular contractions (PVC) within reasonable accuracy and compares favorably to other methods reported in the literature. PMID- 17281521 TI - Combined fetal ultrasonography and magnetocardiography. AB - We discuss the feasibility of combining ultrasound and magnetocardiography for assessment of fetal cardiac function and other fetal monitoring applications. PMID- 17281522 TI - ECG Beat Classification Using Mirrored Gauss Model. AB - Accurate electrocardiogram (ECG) beat classification is essential for automated detection of arrhythmias. A novel classification algorithm of the ECG beats, applying Mirrored Gauss Model (MGM) had been proposed in this paper. The MGM has strong morphological representation ability for QRS complex waves using curve fitting. With the MGM, the width of QRS complex wave could be extracted and applied to ECG beat classification easily, effectively and automatically. It was proved by experiment carrying out using all of ECG records in MIT-BIH Arrhythmia Database that the MGM is a promising algorithm for ECG beat classification. The whole classification accuracy is 93.93% for normal beats and 93.94% for premature ventricular contraction (PVC) beats. PMID- 17281523 TI - Improvement of ventricular mechanical properties by puerarin involves mitochondrial permeability transition in isolated rat heart during ischemia and reperfusion. AB - The aim of the present study was to determine whether the clinically effective cardioprotection conferred by puerarin (Pue) against ischemia and reperfusion is mediated by mitochondrial transmembrane pores and/or channels. In isolated rat hearts subjected to 30 min regional ischemia and 120 min reperfusion, pretreatment with Pue at 0.24 mmol/L for 5 min before ischemia increased myocardial formazan content, an index of myocardial viability, reduced lactate dehydrogenase release, improved recovery of the maximal rise/fall rate of left ventricular pressure, left ventricular end-diastolic pressure and rate-pressure product (left ventricular developed pressure multiplied by heart rate) during reperfusion. Administration of atractyloside (20 micromol/L), an opener of the mitochondrial permeability transition pore, for the first 20 min of reperfusion and 5-hydroxydecanoate (100 micromol/L), the mitochondrial specific ATP-sensitive potassium channel blocker, for 20 min before ischemia, attenuated the protective effects of Pue. In mitochondria isolated from hearts pretreated with 0.24 mmol/L Pue for 5 min, a significant inhibition of Ca2+-induced swelling was observed, and this inhibition was attenuated by 5-hydroxydecanoate. These findings indicate that Pue protects the myocardium against ischemia and reperfusion injury via inhibiting mitochondrial permeability transition pore opening and activating the mitochondrial ATP-sensitive potassium channel. PMID- 17281524 TI - Rutin-induced endothelium-dependent vasorelaxation in rat aortic Rings and the underlying mechanism. AB - The aim of the present study was to determine the possible mechanism by which rutin causes vasodilatation in isolated thoracic aorta rings from the rat. The effects of rutin on rings preconstricted with phenylephrine, with or without endothelium, were determined using an organ bath technique. The mechanism was explored by measuring the effects of the nitric oxide synthase inhibitor L-N(G) nitroarginine methyl ester (L-NAME), the guanylyl cyclase inhibitor methylene blue, the cyclooxygenase inhibitor indomethacin, the ATP-sensitive K+channel blocker glibenclamide and the beta-adrenoceptor antagonist propranolol. Rutin at the range of 10-160 mumol/L caused dose-dependent vasorelaxation in preconstricted endothelium-intact rings, but had no effect on rings without endothelium. The maximal response calculated from the vasorelaxation curves of rutin was 44.28 plus or mines 7.48%. Pretreatment with L NAME (0.1 mmol/L), methylene blue (10 mumol/L), glibenclamide (10 mmol/L) or indomethacin (10 mmol/L) attenuated the vasorelaxation induced by rutin in endothelium-intact rings. Glibenclamide (10 mmol/L) enhanced the vasorelaxation of rutin. Propranolol (10 mumol/L) did not block the effect of rutin. The results indicate that vasorelaxation is induced by rutin via the nitric oxide-guanylyl cyclase pathway and a prostaglandin-mediated mechanism, as well as activation of the ATP-sensitive potassium channel. PMID- 17281525 TI - Effects of 4-hydroxy-2-nonenal on cultured human aortic endothelial cells and myocardial cell. AB - To study the effects of 4-hydroxy-2-nonenal (HNE) on cultured human aortic endothelial cells and myocardial cells so as to explore the mechanism of the pathogenesis of atherosclerosis. In situ cell death technique, quantitative DNA damage detection and immunohistochemistry were used to identify the cell apoptosis and DNA damage in cultured human aortic endothelial cells and myocardial cells. Tail moment was 32.80+/-1.12, 44.30+/-0.99 and 74.6+/-0.97 when HAOEC were treated with 5 muM, 10muM and 15 muM of HNE for 10 hours, which were of statistical significance when compared with the normal group (6.0+/-0.67, P < 0.001 respectively), But when HAOEC was treated with 1 muM of HNE, the tail moment was 11.3+/-0.9, which was of no statistical difference compared with the untreated group(P>0.05). When human aortic endothelial cells (HAOEC) were treated with 5 muM, 10muM and 15 muM of HNE for 10 hours, the percent of nonviable cells were 5.70+/-0.55, 25.96+/-2.02 and 50.80+/-3.40 (P<0.001 respectively when compared with the normal group with the percent of 0.27+/-0.13). But when HAOEC was treated with 1 muM of HNE for 10 hours, the percent of nonviable cells was 2.5+/-0.22, and no difference was observed when compared with the untreated group (P>0.05). When cultured human myocardial cells were treated with 5 muM of HNE for 10 hours, TUNEL staining showed a greater number of apoptotic cells in HNE treated human myocardial cells. No TUNEL-positive cells were observed in untreated group. When HAOEC was treated with 5 muM of HNE for 10 hours, immunocytochemical labeling with polyclonal antibody to HNE-modified proteins revealed specific cytoplasmic staining in cells incubated with HNE, whereas staining was absent in control cells incubated with vehicle. But 1 muM of HNE treatment didn't present positive stainings. Higher concentrations of HNE (10 muM and 15 muM) showed much stronger positive stainings. HNE induces DNA damage and cell apoptosis of cultured aortic endothelial cells and myocardial cells. The DNA damage and apoptosis levels are proportional to the HNE concentrations. PMID- 17281526 TI - A model for intracranial hydrodynamics. AB - This paper presents a model for simulation of intracranial fluid dynamics. The intention is to show how to build a model for this biomedical system by using general techniques known to control engineers. By employing first order principles (like conservation of mass, ...) and constitutive equations, the ;biological' control loops are interpreted in a technical manner allowing to study the behaviour of the biological system in a simulation environment and to get a better understanding without harming a single patient. PMID- 17281527 TI - Numerical simulation of air flow in the human nasal cavity. AB - A highly automated method was used to construct numerical models of six 3-D human right nasal cavities from computed tomography data. Steady state airflow simulations were performed with computational fluid dynamics software for quiet breath on the six models. The method is validated with particle simulations. Simulation results from each of the six studies are compared. PMID- 17281528 TI - Identification of apparently acausal stiffness models. AB - Discretization of dynamic stiffness models is shown to produce an a-causal impulse response. Expressions are derived for discrete-time impulse responses of first-and second-order derivatives. Enforcing periodicity gives rise to anti causal components in these models. These models are used to describe the anti causal components in identified stiffness models. PMID- 17281529 TI - Identification of quadratic nonlinear models oriented to genetic network analysis. AB - The goal of this paper is to provide a novel procedure for the identification of nonlinear models which exhibit a quadratic dependence on the state variables. These models turn out to be very useful for the description of a large class of biochemical processes with particular reference to the genetic networks regulating the cell cycle. The proposed approach is validated through extensive computer simulations on randomly generated systems. PMID- 17281530 TI - Efficacy of using mean arterial blood pressure sequence for linear modeling of cerebral autoregulation. AB - Linear autoregressive (ARX) models are often used to describe the dynamic cerebral autoregulation in humans by relating cerebral blood flow velocity (CBFV) to beat-to-beat mean arterial blood pressure (MABP). For linear model estimation it is required that the input be persistently exciting. This study aimed to establish if the MABP is adequately persistently exciting for estimating to yield a linear model. Using ARX models with MABP as input and CBFV as output, linear models for 11 healthy normal subjects in supine position were obtained. The order of the models was allowed to vary between 1 to 10. For each subject, the model with the least mean squared error (MSE) value was selected, called Ma. Ma was then treated as the unknown model of the cerebral autoregulation to be estimated. Ma was separately subjected to the measured MABP as well as a pseudo random binary sequence (PRBS) to estimate two ARX models for it. The resulting estimates of Ma with the lowest MSE were selected as Me1 and Me2, respectively. With the measured MABP as input, the MSE values between the resulting output of Me1 and Me2 and the measured CBFV were calculated. These MSE values were compared to the MSE value previously obtained for Ma to determine if Me1 that was obtained using MABP can estimate CBFV with the same level of accuracy as Me2. This analysis was carried out both with the traditional 6 minutes data and was repeated by dividing the 6 minutes of data into four 1.5 minute sections, a total of 5 comparisons. The analysis showed that the computed MSE values for Ma, Me1 and Me2 were the same for each subject, irrespecteve of the duration of the data set used for the study. However, the orders of the models were not identical. For each of the three models the average MSE value for 11 subjects was 0.0200 for 6 minutes,0.0235 for first 1.5 minute and 0.0263, 0.0278 and 0.0255 for secon, third and fourth 1.5 minutes, respectively. Results suggest that 1.5 minutes of MABP sequence is adequate as input for estimating linear models of cerebral autoregulation. PMID- 17281531 TI - Weighted fuzzy classification with integrated learning method for medical diagnosis. AB - Medical diagnosis can be viewed as a pattern classification problem: based a set of input features the goal is to classify a patient as having a particular disorder or as not having it. Performance of medical diagnosis is typically assessed in terms of sensitivity and specificity. In this paper we introduce a pattern classification system for medical diagnosis that is based on fuzzy logic and utilises weighted training patterns. Adjusting the weights allows to focus either on sensitivity or specificity while not neglecting the other one and hence lends a degree of flexibility to the diagnostic process. A learning method is utilised that provides improved classification performance. Excellent classification results based on the University of Wisconsin breast cancer database are presented. PMID- 17281532 TI - Noise removal of ECG S signals using Legendre moments. AB - This paper proposes a method to remove the noise in the ECG (Electrocardiogram) signals using Legendre moments. Noise is removed in the reconstructed ECG signals when lower order Legendre moments are used. RMSE (Root Mean Square Error) is used as the distortion measure for the reconstructed ECG signals. With sampling rate of 256 Hz and number of moments used is 13% of the data in each interval, experimental results show that reconstruction of ECG signal using Legendre moments can produce a smoother signal without noise while maintaining signal quality that is acceptable to cardiologist. PMID- 17281533 TI - Estimation of hidden state variables of the intracranial system using constrained nonlinear Kalman filters. AB - Impeded by the rigid skull, direct assessment of physiological variables of the intracranial system is difficult. A hidden state estimation approach is designed in the present work to facilitate the estimation of unobserved variables from available clinical measurements including intracranial pressure (ICP) and cerebral blood flow velocity (CBFV). The estimation algorithm is based on a modified nonlinear intracranial mathematical model, whose parameters are first identified in an offline stage using a nonlinear optimization paradigm. Following the offline stage, an online filtering process is performed using a nonlinear Kalman filter-like state estimator that is equipped with a new way of deriving the Kalman gain using the physiological constraints on the state variables. It is shown in the present work that changes of nominal radii of the proximal and distal cerebral arterial vascular beds could be tracked by using the proposed hidden state estimator. PMID- 17281534 TI - On the optimal extraction of neural correlates of binaural interaction for bilateral cochlear implant adjustments. AB - Accessible neural correlates of binaural interaction might be useful for the objective adjustment of cochlear implants in a bilateral implantation. A possible candidate could be the beta-wave of binaural interaction components in auditory brainstem responses which has been shown to be an objective measure of binaural interaction. However a reliable and automated detection of this component capable of clinical use still remains a challenge and, moreover, it is mainly applied as discrete decision measure which does not allow for a quantitative assessment of binaural interaction. In this correspondence, we suggest a continuous time-scale feature of binaurally evoked brainstem responses for the quantitative assessment of binaural interaction in bilateral cochlear implant users. The extraction of such a feature by morphological local discriminant bases has recently been introduced in the objective diagnosis of the central auditory processing disorder. We show that this feature could be optimal for the adjustment of cochlear implants in the sense that it is continuous and allows for a machine based analysis. It is concluded that morphological local discriminant bases allow for the extraction of a continuous time-scale correlate of binaural interaction which seems to be applicable to objective bilateral cochlear implant adjustments. PMID- 17281535 TI - Filtering electrocardiogram signals using the extended Kalman filter. AB - In this paper the Extended Kalman Filter (EKF) has been used for the filtering of Electrocardiogram (ECG) signals. The method is based on a previously nonlinear dynamic model proposed for the generation of synthetic ECG signals. The results show that the EKF may be used as a powerful tool for the extraction of ECG signals from noisy measurements; which is the state of the art in applications such as the noninvasive extraction of fetal cardiac signals from maternal abdominal signals. PMID- 17281536 TI - An improved mean frequency estimator for ultrasonic color flow imaging using second-order autoregressive model. AB - An improved second-order AR estimator is proposed for color flow imaging. It can give accurate estimation in the presence of very intensive clutter signal. Traditionally, the performance of the second-order AR estimator may be degraded by the clutter when the amplitude of the clutter is very large compared with the Doppler signal, because very large clutter will shift the Doppler pole toward low frequency. The improved second-order AR estimator which we propose in this paper can remedy this problem by first estimating the mean frequency of the clutter signal and then compensating the frequency down-shift of the Doppler signal using this mean frequency. Simulation results show that the improved AR estimator can give more accurate estimate of the mean frequency and variance of the blood signal than the conventional one, even if the amplitude of the clutter is very large compared with Doppler signal. PMID- 17281537 TI - Comparison of time-variant coherence algorithms in single-trial: a dynamic analysis. AB - Synchronization in the electroencephalogram, which can be quantified by time variant coherence measures, reveals a communication between brain regions reflecting different functions (e.g. learning or memory). Aim of this work is to compare three time-variant coherence algorithms in single-trial. The first algorithm is based on the short-time Fourier transform, the second one on the adaptive discrete Fourier transform, whereas the third algorithm is based on a recursive smoothed pseudo Wigner-distribution. Parameters which describe the dynamic properties of the algorithms were calculated and compared on simulated data. Differences were observed in the estimation performance of the algorithms. Based on the obtained results, the algorithms are discussed for their utilization in future applications. PMID- 17281538 TI - Noninvasive diagnosis of coronary artery disease based on instantaneous frequency of diastolic murmurs and SVM. AB - Noninvasive diagnosis method of Coronary artery disease is proposed based on the instantaneous frequency estimate of diastolic murmurs and Support Vector Machine(SVM) classifier. Hilbert-Huang transform is studied to analyze the instantaneous frequency of diastolic murmurs. The weighted instantaneous frequency is introduced. Using statistical quantities of weighted instantaneous frequency forms feature vectors. In end the SVM classifier is build for diagnosis of CAD. 77 clinical recordings (40 abnormal and 37 normal) are categorized as two groups: training sets (20 abnormal and 20 normal) which are employed to train the classifier and test sets (20 abnormal and 17 normal) which are employed to test the classifier. 17 of 20 abnormal and all normal are correctly diagnosed. The results show that the method offers a promising prospect for early noninvasive diagnosis of CAD. PMID- 17281539 TI - Multiple cardiac arrhythmia recognition using adaptive wavelet network. AB - This paper proposes a method for electrocardiogram (ECG) heartbeat pattern recognition using adaptive wavelet network (AWN). The ECG beat recognition can be divided into a sequence of stages, starting from feature extraction and conversion of QRS complexes, and then identifying cardiac arrhythmias based on the detected features. The discrimination method of ECG beats is a two-subnetwork architecture, consisting of a wavelet layer and a probabilistic neural network (PNN). Morlet wavelets are used to extract the features from each heartbeat, and then PNN is used to analyze the meaningful features and perform discrimination tasks. The AWN is suitable for application in a dynamic environment, with add-in and delete-off features using automatic target adjustment and parameter tuning. The experimental results obtained by testing the data of the MIT-BIH arrhythmia database demonstrate the efficiency of the proposed method. PMID- 17281540 TI - Unsupervised classification in uterine electromyography signal: toward the detection of preterm birth. AB - The purpose of this study is to classify the uterine contractions in the electromyography (EMG) signal. As the frequency content of the contraction changes from one woman to another and during the pregnancy, wavelet decomposition is used to extract the parameters of each contraction, and an unsupervised statistical classification method based on competitive artificial neural network is then used to classify events. A principal component analysis projection is then used to evidence the groups resulting from this classification. Results show that uterine contractions may be classified into independent groups according to their frequency content and so according to the pregnancy terms. This classification will be used to detect the preterm birth. PMID- 17281541 TI - Hybrid feature vector extraction in unsupervised learning neural classifier. AB - Feature extraction and selection method as a preliminary stage of heart rate variability (HRV) signals unsupervised learning neural classifier is presented. Multi-domain, mixed new feature vector is created from time, frequency and time frequency parameters of HRV analysis. The optimal feature set for given classification task was chosen as a result of feature ranking, obtained after computing the class separability measure for every independent feature. Such prepared a new signal representation in reduced feature space is the input to neural classifier based on introduced by Grosberg Adaptive Resonance Theory (ART2) structure. Test of proposed method carried out on the base of 62 patients with coronary artery disease divided into learning and verifying set allowed to chose these features, which gave the best results. Classifier performance measures obtained for unsupervised learning ART2 neural network was comparable with these reached for multiplayer perceptron structures. PMID- 17281542 TI - Implications for healthcare knowledge management systems: a case study. AB - The notion of incorporating knowledge management (KM) in the healthcare sector has recently witnessed a lot of interest, both from healthcare practitioners and scholars. Because KM for healthcare has just started to appear on the radar of healthcare stakeholders, there exists very limited research (particularly empirical data) to guide healthcare stakeholders, both from an academic and organizational perspective. This paper attempts to contribute to the adoption of KM in the clinical and healthcare sectors by collecting and analyzing data on technological, organizational and managerial perspectives on KM in these sectors. This paper provides an analysis of a case study which looks at current practices towards healthcare information management. PMID- 17281543 TI - Management of medical technology - implementation issues. AB - Medical technology in Australian public hospitals has a replacement cost of approximately A$3 billion. The management of this invaluable asset suggests the need for a planning framework to facilitate equipment replacement and acquisition decisions, an accurate inventory of technology assets, and an implementation process to enable prioritisation and the allocation of funds. The authors report on work associated with the initial phases of planning process development and identify issues that need to be resolved in relation to the implementation phase. PMID- 17281545 TI - Diagnostic hysteroscopy video summarization and browsing. AB - Diagnostic hysteroscopy videos are continuous (non-interrupted) video sequences, usually recorded in full. However, only a few segments of the recorded videos are relevant from the diagnosis/prognosis point of view, and need to be evaluated and referenced later. This paper proposes statistical techniques to identify clinically relevant segments in diagnostic hysteroscopy videos, and their associated key-frames to create a rich video summary which supports video browsing. Our preliminary experimental results indicate that our method produces video summaries containing a super set of the clinically relevant video segments. A promising experimental result is that when specialists summarize the same videos manually, they usually choose from segments contained in our video summary. PMID- 17281546 TI - Building hospital EPR with IHE technical framework. AB - This presentation gives an approach to build EPR (Electronic Patient Record) by using the model of Cross-Enterprise Clinical Documents Sharing (XDS) of IHE, which enables a number of information systems to share clinical records during patients' care delivery activities. The EPR establishes a collaborative mechanism to group medical records according to a variety of reasons (e.g. a visit, a case) and provides Document Consumers (e.g. a physician, a radiologist) with an easy way to access the specific clinical documents of interest from this longitudinal cross-system record. PMID- 17281544 TI - A quantitative system for pulse diagnosis in Traditional Chinese Medicine. AB - The pulse diagnosis is one of the most important examinations in Traditional Chinese Medicine (TCM). Due to the subjectivity and fuzziness of pulse diagnosis in TCM, quantitative systems or methods are needed to modernize pulse diagnosis. But up to now, the effective models that can classify pulse types according to pulse waves automatically have not been reported, which undoubtedly limits the practical applications of pulse diagnosis in clinical medicines. In this article, a novel quantitative system for pulse diagnosis was constructed based on Bayesian networks (BNs) to build the mapping relationships between pulse waves and pulse types. The results show that the system obtains relative reliable predictions of pulse types, and its predictive accuracy rate reach 84%, which testifies that the model used in our system is feasible and effective and can be expected to facilitate popular applications of TCM. PMID- 17281547 TI - Cost-effectiveness index modeling for a hospital unit. AB - The healthcare expenditures around the world are claiming bigger and bigger share of a country GDP each year. However, the effectiveness of the healthcare system compared to the ever-rising healthcare expenditures is not clearly defined and compared. A generic model of cost-effectiveness index is developed for a hospital unit (department). The cost-effectiveness index (CEI) consists of the total operating costs (TOC) and total effect index (TEI). TEI consists of healthcare productivity index (HcPI), health status index (HSI), healthcare quality index (HcQI) and healthcare efficiency index (HcEI). All of the effect measures are in different dimensions, thus index number method was applied to convert the effect measures into non-dimensional numbers that can be summed or subtracted. The CEIs obtained are relative among a few different hospitals. The CEIs can be a performance assessment tool to compare the operation of different hospital, and subsequently act as a motivation tool to drive for improvement. PMID- 17281549 TI - Non-Invasive imaging of small-animal tumors: high-frequency ultrasound vs. MicroPET. AB - Tumor volume measurement on small animals is important but currently invasive. We employ ultrasonic micro-imaging (UMI) in this study and demonstrate its feasibility. In addition, we use small animal positron emission tomography (microPET) as a preliminary effort to develop multi-modality small animal imaging techniques. The tumor growth curve from UMI is also compared to radioactivity from microPET. Both UMI and [18F] FDG microPET imaging were performed on C57BL/6J black mice bearing WF-3 ovary cancer cells at various stages from the second week till up to the eighth week. Segmentation and 3D reconstruction were also done. The growth curve was obtained in vivo noninvasively by UMI. The cell doubling time was 7.46 days according to UMI. This result was compared with vernier caliper measurement and radioactivity counting by microPET. In microPET, we obtained the time-activity curves from the tumor and the tumor-surrounding tissue. The tumor-to-normal-tissues ratios reached maximum at the fifth week after tumor cell implantation. PMID- 17281548 TI - A viral envelope as a vehicle for tracer, drug, and gene delivery: initial biodistribution study using PET imaging. AB - Viral envelopes can be used as an effective vehicle to deliver imaging tracers as well as therapeutic drugs and genes. However, the current methods for in vivo tracking of viral envelopes are limited. This purpose of this study is to investigate dynamically the in vivo biodistribution of viral envelopes using positron emission tomography (PET) imaging. The hemagglutinating virus of Japan envelope (HVJ-E) was labeled with radioactive fluorine (F-18) for tracking with PET imaging. Due to the low molecular weight of F-18, the encapsulation process by HVJ-E was optimized using the cationic agent poly-L-lysine (PLL, MW 66.7 kDa) and Feridex, a magnetic resonance imaging tracer. After labeling, HVJ-Es were injected intravenously into the normal rat and followed for 2 h using high resolution PET imaging. Region of interest analysis showed a significant increase in average liver accumulation based on radioactivity as compared to all control subjects. Average brain uptake showed a significant increase in radioactivity as compared to control subjects receiving F-18-PLL complexes or F-18 alone. Control subjects showed F-18 uptake primarily in the bones. These results demonstrate a molecular imaging technique that can be used to monitor drug and gene delivery and evaluate potential targeting mechanisms. PMID- 17281550 TI - Diffraction enhanced X-ray imaging for observing guinea pig cochlea. AB - Diffraction enhanced imaging (DEI) is a novel x-ray radiographic imaging method, which derives contrast from absorption, refraction, and extinction. With DEI technique, the spatial resolution of the acquired image can be increased 1000 times over conventional x-ray radiography. Therefore, it is suitable for the observation of biomedical micro-tissues and organs. This paper presents a new imaging method of minute biomedical organs based on DEI technique. In the investigation, the cochleae of guinea pigs were used as the samples. Before imaging, the cochleae of guinea pigs underwent different treatments, including fixation, decalcification, staining with silver nitrate solution, and reduction. Of them, the decalcification of cochleae is very important for improving the imaging quality. Compared with the conventional radiography image much higher contrast is achieved in the obtained DEI images. The fine spiral structure and inner details of the cochlea can be displayed clearly. The results show that compared with the conventional x-ray radiography, DEI is a more effective way of observing the guinea pig cochlear microstructures and other minute biomedical organs, and a potential tool for diagnosing cochlear diseases and morphologic study. PMID- 17281551 TI - Liposomal contrast agent for CT imaging of the liver. AB - A liposomal CT contrast formulation with high iodine loading capacity was developed. The multivesicular liposome (MVL) structure was adopted and the encapsulated iodine concentrations were higher than 50mg/ml. Small MVLs were made with mean diameter at less than 5 micron. They were shown to distribute evenly in the hepatic sinusoid between hepatic plates and the endothelium after intravenous injection. A significant and persistent enhancement of CT value in the liver was observed in CT imaging studies. Compared to conventional extracellular iodine agents Iohexol, the MVL formulation is easier to administer, requires much lower doses, however the resulted liver imaging enhancement is greater and last longer. Therefore, we believe it has great potentials as a new and superior contrast enhancement agent for CT imaging of the liver. PMID- 17281552 TI - Imaging on the binding of FITC-insulin with insulin receptors in cortical neurons of rat. AB - It has been identified that insulin was present in the central nervous system (CNS) with some types of action there, and it exerted important actions within the brain and functions as neuropeptide. Insulin should bind with insulin receptors (IR) to perform its functions, so it is important to study the binding of insulin with IR in neurons. A direct imaging method was developed by fluorescence microscopy. HepG2 cells were firstly selected to be the model for methodological study, the results showed that insulin could bind with IR at the membrane of the studied cells after incubated 1 minute with the cells. In order to show the binding of insulin with IR in neurons, the cultured cortical neurons of rat were selected as representative. It was found that insulin could bind with IR at the membrane of the neurons, and IR distribute not only on the somas, but also on the neurites. Using fluorescent imaging to directly detect the binding of insulin with IR in neurons could be promising for further study of insulin functions in brain. It is rarely reported the direct imaging on the binding of insulin with IR of neurons by microcopy system in live cells. PMID- 17281553 TI - Identification of a new protein from silkworm pupas by biological mass spectrometry. AB - To find out the efficient peptide of selenium-rich silkworm pupas in inducing the apoptosis of hepatoma cells, selenium-containing proteins were isolated and characterized. One of the two major proteins in selenium-rich silkworm pupas was identified to be a new protein by peptide mass fingerprinting on matrix assisted laser desorption ionization - time of flight - mass spectrometry. Amino acid sequences of peptides digested by trypsin from the new protein were determined by capillary liquid chromatography - electrospray ionization - quadrupole/time of flight - mass spectrometry and searched with Mascot in NCBI database. Results showed that the six major peptides from the protein were also new peptides that could not be found in the database up to date. PMID- 17281554 TI - Equivalent contractility indexes for the assessment of left ventricular systolic function in post-AMI human hearts. AB - We propose new contractility indexes, in the work, which are equivalent to the conventional contractility (Ees) determined with the slope of left ventricular (LV) end-systolic pressure-volume relation. Nineteen patients with acute myocardial infarction (AMI) were recruited in the study. They received thrombolytic therapy within 24 hours after the AMI event, and their LV pressures and volumes were measured with Millar and multi-electrode volume conductance catheters during catheterization examination at the first week and 3 months, respectively. The first equivalent contractility index (eEsv) submitted was defined as the Ees divided by the end-systolic volume (ESV) and normalized to 100 ml, the second (eEdv) as the Ees divided by the end-diastolic volume (EDV) and normalized to 100 ml, and the third (eEmv) as the Ees divided by the midrange of the LV volume and normalized to 100 m. Using linear regression methods, we found that a high correlation coefficient (r > 0.82) exists between the Ees and one of the three new contractility indexes. Furthermore, the eEsv but not Ees was significantly higher measured at 3 months than at one week after thrombolysis. In conclusion, an increase in the equivalent contractility eEsv implies the improvement of the left ventricular systolic function in the post-AMI human hearts long-term after thrombolytic intervention, as the size-dependence of contractility is taken into account. PMID- 17281555 TI - Cardiac force and muscle shortening in regional ischemia: asynchronization and possible uncoupling. AB - Acute myocardial ischemia affects both cardiac muscle force development and shortening in the affected regions. The exact mechanisms are unclear. We investigated myocardial function during ischemia and reperfusion both experimentally and with a muscle fiber model. The model was subjected to perturbations in contractility and force activation. Results show that the cardiac muscle model reflects many of the physiological changes observed in myocardial ischemia and reperfusion. Asynchronization between force generation and muscle shortening observed during regional ischemia and reperfusion may be dependent on the extent of their uncoupling. PMID- 17281556 TI - Determination of the left ventricular myofiber angle analytically and its significance. AB - It is known that the tremendous internal pressure build-up in the left ventricle (LV) cavity during isovolumic contraction is due to the contraction of the spirally woven myocardial fibers. In this paper, a biomathematical model is developed to investigate the fiber angle using the theory of elasticity. Simultaneously, another simplified model in order to reduce the mathematical complexity was also developed to determine the fiber angle. The results of these two models showed that both the myocardial fiber angles are in same magnitude. PMID- 17281557 TI - Nitric oxide participates in the negative inotropic effect of interferon-alpha in rat cardiac muscle. AB - In clinical practice, interferon-alpha (IFN-alpha) has been widely used as an antiviral, antitumor and immunomodulatory agent. However, its intravenous administration at large doses is associated with significant cardiovascular side effects such as congestive heart failure and myocardial infarction. But the direct cardiovascular effects of IFN-alpha and the underlying mechanisms are not clear. In this study, we investigated the effects of IFN-alpha on contractility in Langendorff perfused rat hearts and isolated rat papillary muscles. The results showed that IFN-alpha induced a concentration-dependent negative inotropic effect in the isolated heart and papillary muscle. Pretreatment with L NAME, a nitric oxide synthase inhibitor, attenuated this inotropic effect. Furthermore, in isolated papillary muscles IFN-alpha decreased the responsiveness to the beta-agonist isoproterenol, which was also attenuated by pretreatment with L-NAME. In conclusion, these results show that IFN-alpha induced a negative inotropic effect in normal and beta-adrenergic activated cardiac muscle at least partly via nitric oxide (NO). PMID- 17281558 TI - Relationship between the left ventricular elastance and the effective arterial elastance in AMI patients after thrombolysis. AB - The purpose of the study is to investigate the effect of thrombolysis on the relationship between the left ventricular (LV) maximum elastance (Emax) and effective arterial elastance (Eart) in 20 patients with acute myocardial infarction (AMI). LV pressures and volumes of the patients were measured with Millar and multi-electrode volume conductance catheters during catheterization examination, respectively, at the first week and 3 months after the thrombolytic treatment. Emax was represented by the slope of the LV end-systolic pressure volume relation, and Eart by the slope of the arterial end-systolic pressure stroke volume relation. The results showed a linear Emax to Eart relation (r = 0.59) at the 1st week, but not 3 months (r =0.20), in those post-AMI patients. Moreover, the Emax was found to be linearly proportional to the Emax/Eart ratio at both the 1st week (r = 0.88) and 3 months (r = 0.85) after thrombolytic therapy. In summary, a 'stunt' hearts in the initial period after thrombolytic intervention reveals a linear relationship between the ventricular contractility and afterload, suggesting that the coupling of the left ventricle and arterial vasculature seems to be maintained. PMID- 17281559 TI - A simultaneous framework for recovering three dimensional shape and nonrigid motion from cardiac image sequences. AB - Quantitative assessment of the shape and motion variability of the heart has important implications for the diagnosis and treatment of cardiac diseases. In this paper, we present a unified methodology which simultaneously recovers the shape and motion of the left ventricle, including the endo-, epi-, and mid-wall myocardium. The left ventricle is modeled as an isotropic linear elastic material, and represented by volumetric mesh constructed from the Delaunay triangulation of the sampling points. Specifically, the evolution forces imposed on the myocardium are individually constructed for each nodal point through the integration of the data-driven edginess measures, the prior spatial distributions of the myocardial tissues, the temporal coherence of the image-derived salient features, and the cyclic motion characteristics of the heart. The dense displacement field can then be estimated when the total energy of the elastic body is minimized at equilibrium. Experiments on 3D human magnetic resonance image sequences of heathy and pathological subjects show the accuracy and robustness of the strategy. PMID- 17281560 TI - Identification of vigilance lapses using EEG/EOG by expert human raters. AB - It is critically important for certain occupational groups to remain highly alert throughout their working day. For safety reasons, it would be useful to automatically detect lapses in performance using EEG/EOG. Automating the detection process could be simplified considerably if we could mimic human experts. Surprisingly, it is unclear to what extent human EEG raters are able to detect lapses. Consequently, we undertook a study in which 4 expert EEG raters assessed the level of alertness of 10 air traffic controllers by observing a combination of their EEG and EOG while they performed a 10 min psychomotor vigilance task (PVT). They were specifically required to identify lapses or sleep episodes that might lead to a lapse in PVT performance. A reaction time .. 500 ms was defined as a PVT lapse. There was a total of 101 lapses (mean duration = 1.00 s). Of these, only 6 lapses were detected by one or more raters and all of these were marked as ;sleep'. Overall the human expert raters were unable to reliably identify lapses based only on EEG and EOG. This poor performance suggests an automated system would need to identify subtle features not overtly visible in the EEG. PMID- 17281561 TI - Monitoring driver's alertness based on the driving performance estimation and the EEG power spectrum analysis. AB - Preventing accidents caused by drowsiness behind the steering wheel is highly desirable but requires techniques for continuously estimating driver's abilities of perception, recognition and vehicle control abilities. This paper proposes methods for drowsiness estimation that combine the electroencephalogram (EEG) log subband power spectrum, correlation analysis, principal component analysis, and linear regression models to indirectly estimate driver's drowsiness level in a virtual-reality-based driving simulator. Results show that it is feasible to quantitatively monitor driver's alertness with concurrent changes in driving performance in a realistic driving simulator. PMID- 17281562 TI - Fractal dimension of the EEG for detection of behavioural microsleeps. AB - The fractal dimension (FD) of EEG has been shown to be of value in the detection of epileptic seizures. In this paper, we assess its usefulness in detecting behavioural microsleeps. Fifteen non-sleep-deprived normal subjects performed two 1-hour sessions of a continuous tracking task while EEG, EOG and facial video were recorded. Higuchi's algorithm was used to calculate the FD of the EEG. Video lapses were scored independently from tracking performance by a human rater. A subset of data was rated independently by three human raters observing both tracking performance and the video rating to identify behavioural microsleep events. The mean point-biserial correlation between FD and the mean human rating was -0.213 indicating modest agreement. Crossvalidated detection performance of the FD was poor with a mean correlation (.. = -0.099). This suggests that, on its own, FD of the EEG is unlikely to be useful for detecting microsleeps. PMID- 17281563 TI - A Neuro-behavioral test and algorithms for quantification of sleepiness and characterization of wake-sleep transitions. AB - A neuro-behavioral test has been developed that quantifies sleepiness by means of a convenient and relatively short-duration (15 minute) protocol, and using a class of algorithms that track wake to sleep transitions. Utilizing an ambulatory EEG monitoring combined with an auditory-based vigilance test, this method acquires both behavioral response (i.e., reaction time) and EEG waveforms that are simultaneously analyzed to produce a time-varying EEG-based Drowsiness Sleepiness Index (DSI). DSI index is computed from the time-varying power spectrum of EEG using an algorithm whose coefficients were determined based on an optimization procedure that maximized the correlation between the time profiles of DSI and those of the behavioral response. Sleepiness is quantified using an algorithm based on the consistency of the neuro-behavioral indices over the test period as well as the degree and profile of their degradation when the subject is incapable of maintaining alertness. This test was administered to 5 volunteers (separate from the subjects whose data were used for the above optimization of DSI) under the conditions of adequate prior night sleep and sleep restriction. Cross correlation analysis showed a close agreement between the time profiles of EEG-based DSI and behavioral response indices. Statistical analysis showed significant difference between the alert and sleepy conditions for the whole group as well as in each individual subject. PMID- 17281564 TI - Analyzing event-related brain dynamics in continuous compensatory tracking tasks. AB - The dynamics of electroencephalographic (EEG) activity in continuous compensatory tracking tasks were analyzed by independent component analysis (ICA) and time frequency techniques. In one-hour sessions, 72-channel EEG was recorded while a healthy volunteer attempted to use a trackball to keep a drifting disc in a bulls eye in the center of screen. Disc trajectory was converted into a moving measure of disc error. Local minima (perigees) indicated moments when the disc started to drift away from the center. Subject performance was indexed by root mean square disc error in a 20s epoch centered on each perigee, high error generally indicating drowsiness. Maximally independent EEG processes and their equivalent dipole source locations were obtained using the EEGLAB toolbox (http://sccn.ucsd.edu/eeglab). Component activations were epoched in 5s time intervals time locked to perigees. Following disk perigees during (drowsy) periods of high disk error, significant spectral changes were observed. One of the 70 independent components was located in or near primary visual cortex. During periods of poor (drowsy) performance, it had increased mean tonic alpha/theta activity, with a further phasic alpha/theta increase following perigees [1,2]. At the same time, low alpha activity of a second component located in or near cingulate gyrus increased, and 10-30 Hz EEG activity of a third component in the left somatomotor cortex increased briefly. The alpha activity of the somatomotor component persisted through the following distance maximum. These spatiotemporal phenomena were consistently observed across three sessions within subjects. Thus, event-related EEG brain dynamics can be detected and modeled in a continuous behavioral task without impulsive event onsets. PMID- 17281565 TI - Detecting behavioral microsleeps using EEG and LSTM recurrent neural networks. AB - Lapses in visuomotor performance are often associated with behavioral microsleep events. Experiencing a lapse of this type while performing an important task can have catastrophic consequences. A warning system capable of reliably detecting patterns in EEG occurring before or during a lapse has the potential to save many lives. We are developing a behavioral microsleep detection system which employs Long Short'Term Memory (LSTM) recurrent neural networks. To train and validate the system, EEG, facial video and tracking data were collected from 15 subjects performing a visuomotor tracking task for 2 1-hour sessions. This provided behavioral information on lapse events with good temporal resolution. We developed an automated behavior rating system and trained it to estimate the mean opinion of 3 human raters on the likelihood of a lapse. We then trained an LSTM neural network to estimate the output of the lapse rating system given only EEG spectral data. The detection system was designed to operate in real-time without calibration for individual subjects. Preliminary results show the system is not reliable enough for general use, but results from some tracking sessions encourage further investigation of the reported approach. PMID- 17281566 TI - Wide FOV wedge prism endoscope. AB - We.. have developed a novel robotic endoscope system. It can be used to observe a wide field of view without moving or bending the whole endoscope system. .. It consists of a rigid endoscope and two wedge prisms at the distal tip. Rotating each wedge prism respectively, we can change the direction of view. Accordingly it becomes possible to observe a wide field of view even in a small space, and suited to clinical uses because it does not damage body tissues or internal organs. .. Wedge prisms are designed to avoid vignetting which is caused by the refraction or the reflection at prisms. The endoscope has 10mm in diameter, and the drive unit is simply separable for the sterilization. In addition, since it has a simple and small drive unit, it does not obstruct surgeon or other surgery robots. The maximum movement of local field of view is 19degrees, and global field of view is 93degrees. In the evaluation experiment, we conformed that both of the image quality and the performance are acceptable. PMID- 17281567 TI - Robotic system for microsurgical keratoplasty. AB - Robotic system is developed to improve the effect of microsurgery for keratoplasty. Based on task and motion analysis in the surgery, type synthesis and size synthesis of robotic mechanism are performed to meet the requirements of surgical tasks. Force and position microsensors are integrated on the end effector of microsurgical robot. The two digital filtering methods suitable for the PC and the sensor data board respectively are presented. A feasible method of calibration and reconstruction for surgical microscope is adopted to implement the guidance of robotic vision. The estimated coefficients by linear regression are evaluated for preciseness and robustness. The experiment results show that the robotic system for microsurgical keratoplasty can fulfill the surgical task of corneal trephination precisely. PMID- 17281568 TI - Effects of velocity modulation during surgical needle insertion. AB - Precise interstitial intervention is essential for many medical diagnostic and therapeutic procedures. But accurate insertion and placement of surgical needle in soft tissue is quite challenging. The understanding of the interaction between surgical needle and soft tissue is very important to develop new devices and systems to achieve better accuracy and to deliver quality treatment. In this paper we present the effects of velocity (linear, rotational, and oscillatory) modulation on needle force and target deflection. We have experimentally verified our hypothesis that needle insertion with continuous rotation reduces target movement and needle force significantly. We have observed little changes in force and target deflection in rotational oscillation (at least at lower frequency) of the needle. PMID- 17281569 TI - A miniature cable-driven robot for crawling on the heart. AB - This document describes the design and preliminary testing of a cable-driven robot for the purpose of traveling on the surface of the beating heart to administer therapy. This methodology obviates mechanical stabilization and lung deflation, which are typically required during minimally invasive cardiac surgery. Previous versions of the robot have been remotely actuated through push pull wires, while visual feedback was provided by fiber optic transmission. Although these early models were able to perform locomotion in vivo on porcine hearts, the stiffness of the wire-driven transmission and fiber optic camera limited the mobility of the robots. The new prototype described in this document is actuated by two antagonistic cable pairs, and contains a color CCD camera located in the front section of the device. These modifications have resulted in superior mobility and visual feedback. The cable-driven prototype has successfully demonstrated prehension, locomotion, and tissue dye injection during in vitro testing with a poultry model. PMID- 17281570 TI - Inverse kinematic model of flexure-based microsurgical manipulator. AB - This paper presents the development of an inverse kinematic model for a flexure based micromanipulator using a feedforward neural network. The manipulator is part of an active handheld instrument designed to cancel hand tremor during microsurgery. The manipulator is actuated using three piezoelectric stacks. Preliminary results yield a mean squared error of 5% of the total stack range of motion, and a maximum error of 14% of the total range of motion. PMID- 17281571 TI - Knot-tying with visual and force feedback for VR laparoscopic training. AB - Real-time simulation of thread and knot-tying with visual and force feedback is an essential part of virtual reality laparoscopic training. This paper presents a physics-based thread simulator that enables realistic knot tying at haptic rendering rate. The virtual thread follows Newton's law and behaves naturally. The model considers main mechanical properties of the real thread such as stretching, compressing, bending and twisting, as well as contact forces due to self-collision and interaction with the environment, and the effect of gravity. The structure of the system has essential advantages over geometrically based approaches, as was illustrated in an implementation on the Xitact simulator. PMID- 17281572 TI - Sequential acquisition and processing of perfusion and diffusion MRI data for a porcine stroke model. AB - An automated data processing pipeline, designed for handling a large throughput of sequentially acquired MRI brain data, is described. The system takes as input multiple diffusion weighted (DWI) and perfusion weighted imaging (PWI) volumes acquired at different temporal points, automatically segments and registers them, and ultimately outputs a database used to track various perfusion and diffusion parameters through time at individual brain voxels. This pipeline has been utilized to successfully process two pig brains from an induced stroke experiment. PMID- 17281573 TI - White matter fiber tracking method by vector interpolation with diffusion tensor imaging data in human brain. AB - The directional diffusion information obtained by diffusion tensor magnetic resonance imaging (DT-MRI) can be used to noninvasively visualize white matter fibers in human brain. And it is the unique way to reconstruct those fibers in vivo. However, there are some obstacles for the reconstruction process, e.g., partial volume effect caused by low spatial resolution negatively affects the DT MRI results, and continuous fibers are indicated by the discrete signal on the DT MRI. A fiber tracking algorithm is proposed in this paper. Major eigenvectors and fractional anisotropy (FA) values of the correlative voxels are used for fiber tracking. As a result, this method shows stronger potential to depict the distribution of white matter fibers in human brain. PMID- 17281574 TI - Intravascular effect in velocity-selective arterial spin labeling. AB - Arterial spin labeling (ASL) has been developed into a useful tool for measuring local tissue perfusion with magnetic resonance imaging (MRI). Velocity-selective ASL (VS-ASL) tags spins on a basis of flow velocity, instead of the spatial distribution that is commonly used by conventional ASL techniques. Using a 90 degrees-180 degrees-90 degrees radiofrequency pulse train in combination with flow-sensitive gradients, VS-ASL can potentially generate tags that are very close to the imaging plane and whereby avoid the main error source of conventional ASL techniques coming from T1 relaxation during inflow time (TI). In practice, however, TI of VS-ASL should still be chosen with caution with respect to intravascular signal and cutoff velocity (Vc). With higher Vc, the maximum of VS-ASL signal was observed at shorter TI, which is due to intravacular signal in large vessels. For perfusion measurement in human brain, small Vc (=<2cm/s) is recommended. In contrast to the previous studies that suggested CSF suppression for Vc < 5cm/s, this study used lower amplitude and longer separation of diffusion gradients in the VS pulse train, which reduced b-value and eliminated the necessity of CSF suppression for Vc down to 2 cm/s. PMID- 17281575 TI - Evaluation of hemodynamic perfusion MR images. AB - Perfusion normally refers to the delivery of blood at the level of capillaries. Hemodynamic perfusion magnetic resonance (MR) imaging has been used in clinics for a series of applications including tumor characterization (histological type diagnosis and grading), diagnosis and the follow up of stroke, and several other disorders. For this study a platform to investigate the theoretical basis of perfusion imaging was developed. Using dynamic measurements of contrast agents in magnetic resonance imaging (MRI) relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT) are calculated. These three parameters are quantized, and displayed as color images for diagnostic and follow up studies. The comparative studies in MR perfusion must address issues such as; image registration, region of interest (ROI) selection, threshold identification and quantization of rCBV, rCBF and rMTT. The evaluation process involved the comparison of the diagnostic capabilities of the three perfusion images (rCBV, rCBF, MTT). Digital Substraction angiography was used as the gold standard in these comparisons. The study group comprises 16 patients with the diagnosis of subarachnoid bleeding and intracranial aneurysms. The proposed cerebral MR perfusion analysis system has been accepted by the radiologists as a useful tool for their perfusion studies and clinical evaluation. PMID- 17281576 TI - Characterizing diffusion tensor imaging data with directional entropy. AB - We describe the use of directional entropy (DE) in the directional analysis of diffusion tensor imaging (DTI) data. The directional entropy is a measure of disorder in a directional distribution. It could provide a relatively simple, yet meaningful measure about the brain white matter integrity, complementary to the traditional measures used, such as mean diffusivity or indices of diffusion anisotropy. The challenge of the DTI is to produce measures that would be easily comparable across subject and patient populations. We studied directional distributions and entropy with simulations and measured DTI data. Directional entropy could serve as an additional measure to characterize developmental or pathological states in brain. PMID- 17281577 TI - Spatial frequency dependence of the human visual cortical response to temporal frequency modulation studied by fMRI. AB - The brain response to temporal frequencies (TF) has been already reported, but with no study for different TF in respect to various spatial frequencies (SF). fMRI was performed by 1.5T GE-system in 14 volunteers during checkerboard visual stimulation, with TFs of 4, 6, 8 and 10Hz in low and high SFs of 0.5 and 8cpd. The averaged percentage BOLD signal changes demonstrated the amplitude of the fMRI response to different TFs which was maximally at 6Hz for high SF of 8cpd, and at 8Hz for low SF of 0.5cpd. The results are useful for vision therapy (such as the treatment of Amblyopia) and for fMRI applications incorporating visual tasks. PMID- 17281578 TI - Linear and non-linear features of surface EMG during fatigue and recovery period. AB - To investigate possible factors that affect the sEMG signal features, we analyzed the sEMG signals in bicep bracii (BB) muscle during fatiguing isometric flexions and recovery periods across a range of force levels. Twelve males performed isometric elbow flexions at 40%, 60%, 80% and 100% of their maximal voluntary contraction (MVC) with joint angle keeping at 90deg. And then they performed 3 seconds of MVC at the 2nd, 4th, 6th, 8th , 10th, 20th, 30th, 60th and 120th second respectively during recovery periods. SEMG signals in BB were analyzed using both linear and non-linear methods to get parameters such as average EMG (AEMG), mean power frequency (MPF), Lempel_Ziv complexity (C(n)) and determinism% (%DET). Non-linear parameter C(n) decreased whereas %DET increased during fatiguing flexions. There was no regularity in AEMG in recovery periods. MPF, C(n) and %DET recovered significantly only by seconds rest, and they regressed rapidly in the initial 10 seconds and then slowed down in the later. The rapid changes of SEMG linear and non-linear parameters in recovery periods suggested that central controlling factor may play a more important role in shaping sEMG signals. PMID- 17281579 TI - Muscle force augmentation by low-intensity electrical stimulation. AB - In cases of muscle partial deficiency, force augmentation can be achieved by hybrid activation, i.e., by combining electrical stimulation (ES) with volitional activation. In the present study the volitional and electrically-induced torque components are resolved under visual-feedback activation. Isometric contraction of the tibialis anterior (TA) muscle was studied on 5 healthy subjects, using an activation protocol combining ES alone, volitional activation alone and hybrid activation. Ankle torque and TA EMG were measured. A computational algorithm was developed to dissociate the volitional from the overall torque, based on EMG filtering and on pre-measured calibration curves of volitional torque versus EMG. Based on a defined facilitation factor, the results indicate that within the range of stimulation intensities, there exist regions of increased facilitation of the volitional activation of the TA muscle, in which the torque contribution due to the induced activation is higher compared that of the recruitment curve. PMID- 17281580 TI - Robust and preceding speech detection using EMG. AB - EMG-based VAD is proposed. It is generally known that EMG signals are not affected by acoustic noise and preceding voice. Robust but preceding detection of speech can be expected by using these features. The proposed method extracts one VAD parameter to judge speech or silence from among n EMG signal channels. Experiments are performed to confirm the effectiveness of the proposed method. The results show that some EMG signals reliably precede voice by 30ms or more. Compared with conventional audio VAD, the proposed method seldom drops the speech head and the method's performance is relatively insensitive to background noise. PMID- 17281581 TI - Experimental and analytical investigations of motor unit location for the precise estimation of muscle force with surface electromyograms. AB - Surface motor unit action potential (SMUAP) is generated from a motor unit (MU) located at certain depth from the skin surface. The depth is referred to as MU location in the present papers. The MU location affects the amplitude of MUAP, and smoothed rectified electromyogram (SR EMG) is used to estimate for the muscle force. The aim of this study is to investigate MU locations in the short head of biceps brachii (BIC) and the first dorsal interosseous (FDI), experimentally and analytically with eight-channel surface EMGs (SEMGs) in isometric voluntary contractions. In order to estimate the MU location, profiles of peak SMUAP at each channel were compared with those of different MU locations obtained from the tripole current source model. From the result, MU locations of BIC distributed in a certain range, and those of FDI seemed to be identical. Our method was practical and useful for estimating the approximated MU location. PMID- 17281582 TI - Prediction of four degrees of freedom arm movement using EMG signal. AB - In this paper, we predicted four degrees of freedom movement of a monkey's arm by using a neural network model based on the EMG signal. Through the monkey's reaching task, we measured the electromyograms(EMG) signal from the seven muscles of the arm and simultaneously three dimensional movement trajectory of it. The neural network model used in this study is composed of three layers: the input layer with seven values from the EMG signal of the seven muscles, the middle layer consisted of ten and the output layer of four outputs. The movement predicted by this model was almost the same as the real movement. Besides we could implement no delay interface using the EMG signal that is a fundamental signal from the brain that makes it possible to induce the body's movement. Moreover we can predict not only the external movement of the monkey's arm but also the force of it, which is impossible to be sensed by the external movement sensing devices. PMID- 17281583 TI - Evaluation of muscle activity and fatigue in extensor forearm muscles during isometric contractions. AB - Work-related upper extremity disorders as epycondylitis and tendonitis are closely related to localized muscle fatigue of extensor forearm muscles. The aim of this work is to evaluate levels of activity, fatigue and interactions between the main extensor muscles of the wrist. Surface EMG signals were acquired from extensor carpi radialis (ECR), extensor digitorum comunis (EDC) and extensor carpi ulnaris (ECU) muscles during isometric contractions using linear electrode array technique. Parameters such as muscle fiber conduction velocity (CV), EMG average rectified value (ARV) and frequency parameters were estimated to study muscle activity during selective contractions, during a non specific task at different percentage of the maximum voluntary contraction (MVC) level and during a fatiguing exercise at 50% MVC. Results show that it is possible to enhance significantly ECR and ECU muscle ARV during their selective activation. Moreover, in the non selective task, ECU muscle ARV significantly decreases with respect to the other muscles with the increase of the MVC level. The activity of ECR muscle in a non specific task is predominant with respect to the other muscles at 80%MVC. EMG spectral parameters and CV show fatigue in all muscles during a sustained contraction at 50%MVC. PMID- 17281584 TI - Ventilatory instability during sleep: new insights from the computational model. AB - We developed a computational model of the human respiratory system and its chemoreflex control during sleep [1] [2] Our model, which is an extension of the model of Grodins et al. [3], combines an accurate description of a plant with a novel controller design. The controller consists of two feedback loops (central and peripheral) each with its own delay and gain. The overall minute ventilation is a sum of central and peripheral components. The model was employed to develop a new graphical method for stability analysis of the respiratory control system similar in concept to the phase plane. The relative chemosensitivities of the peripheral and central loops serve as the plane's coordinates. A region of stability exists with the normal operating point for the system lying well inside its boundaries. Changes to the sensitivities of either loop, caused by known pathologies, displace the operating point toward the border of the stability region. Furthermore, the shape and area of the stability region is significantly influenced by changes in the cerebral blood flow. PMID- 17281585 TI - "Optimal" application of ventilatory assist in Cheyne-Stokes respiration: a simulation study. AB - Although a variety of ventilator therapies have been employed to treat Cheyne Stokes respiration (CSR), these modalities do not completely eliminate CSR. As well, most current strategies require that ventilatory assist be provided continuously. We used a computer model of the respiratory control system to determine whether a ventilatory assist strategy could be found that would substantially reduce the severity of CSR while minimizing the application of positive airway pressure. We assessed the effects of different levels of ventilatory assist applied during breaths that fell below selected hypopneic thresholds. These could be applied during the descending, ascending, or both phases of the CSR cycle. We found that ventilatory augmentation equal to 30-40% of eupneic drive, applied whenever ventilation fell below 70% of the eupneic level during the ascending or descending-and-ascending phases of CSR led to the greatest regularization of breathing with minimal ventilator intervention. Application of ventilatory assist during the descending phase produced little effect. PMID- 17281586 TI - Modelling the respiratory chemoreflex control of Acid-base balance. AB - A mathematical model is presented describing the respiratory chemoreflex relations between the partial pressures of carbon dioxide and oxygen at the central and peripheral chemoreceptors and the resulting pulmonary ventilation. These chemoreflex relations in terms of carbon dioxide partial pressures are transformed to relations in terms of hydrogen ion concentrations in brain tissue and arterial blood using the Stewart approach to acid-base balance. In this way, the chemoreflex relations can be expressed in terms of the actual stimulus to the respiratory chemoreceptors. PMID- 17281587 TI - A simple model of dynamic interactions between respiratory centers. AB - There is a general consensus that neurons responsible for the generation of a respiratory rhythm are located in the rostral ventrolateral medulla. However, there is still controversy regarding the necessary components for respiratory rhythm generation. Both inspiratory neurons in the preBotzinger Complex (preBOtC) and pre-inspiratory neurons located more rostrally to this anatomical structure referred to as the parafacial respiratory group (pFRG) have been proposed to be essential for respiratory rhythmogenesis. To study the dynamical interactions between preBOtC and pFRG neurons, we use a canonical model that describes each neuron population as a phase oscillator. We assume that the oscillators are weakly coupled with pFRG neurons providing stimulation to preBOtC neurons and preBOtC neurons providing inhibitory drive to pFRG neurons. In our mathematical study, we explore plausible mechanisms that may account for the complex interactions between I and pre-I neuron. In particular, we show that reduced excitability of inspiratory in preBOtC may lead to the phenomena known as "quantal slowing". PMID- 17281588 TI - Nonassociative learning in expiratory inhibition of inspiratory motor output: an experimental and modeling study. AB - The present study is to characterize the habituation and re-sensitization in the inspiratory inhibition produced by the Botzinger Complex (BOt.C) and the modulation effects of raphe pallidus (RP) and locus coeruleus (LC). Experiments were done on urethane anaesthetized, vagotomized, paralyzed and artificially ventilated rabbits. Electrical stimulation of the BOt.C (25 ..A, 80 Hz, 15 sec) caused inspiratory inhibition that became gradually adapted with the continuation of the stimulation. At the offset of this stimulation, the phrenic discharge showed temporary rebound increase in amplitude. The adaptation-rebound response pattern resembled a neural differentiator. Pre-stimulation of the RP or LC (50 ..A, 80 Hz, 10 sec) facilitated the adaptation of BOt.C's inspiratory inhibition and the post-stimulus rebound. The results indicate the existence of nonassociative learning (habituation and re-sensitization) in the inspiratory inhibition circuit and the modulation of this nonassociative learning by RP and LC. PMID- 17281589 TI - Neural plasticity of respiratory control system: modeling perspectives. AB - Classical models of respiratory control assume a hardwired system architecture with reflex regulation of respiratory rhythm and total ventilation. Recent experimental studies, however, reveal a much more pliable architecture with varying forms of neural plasticity in the afferent and efferent pathways. Here, mathematical models of several types of neural plasticity are proposed and their computational roles in respiratory neural processing are discussed. PMID- 17281590 TI - Nanoelectropulse intracellular perturbation and electropermeabilization technology: phospholipid translocation, calcium bursts, chromatin rearrangement, cardiomyocyte activation, and tumor cell sensitivity. AB - Nanosecond, megavolt-per-meter pulsed electric fields scramble the asymmetric arrangement of phospholipids in the plasma membrane, release intracellular calcium, trigger cardiomyocyte activity, and induce apoptosis in mammalian cancer cells, without the permeabilizing effects associated with longer, lower-field pulses. Dose dependencies with respect to pulse width, amplitude, and repetition rate, and total pulse count are observed for all of these phenomena. Sensitivities vary among cell types; cells of lymphoid origin growing in suspension are more susceptible to nanoelectropulse exposure than solid tumor lines. Simple electrical models of the cell are useful for first-order explanations, but more sophisticated treatments will be required for analysis and prediction at both biomolecular and tissue levels. PMID- 17281592 TI - Electrospun blends of natural and synthetic polymers as scaffolds for tissue engineering. AB - Engineering functional three-dimensional (3-D) tissue constructs for the replacement and/or repair of damaged native tissues using cells and scaffolds is one of the ultimate goals of tissue engineering. In this study, non-woven fibrous scaffolds were electrospun from the synthetic biodegradable polymer poly(lactic co-glycolic acid) (PLGA) and natural proteins, gelatin (denatured collagen) and elastin. In the absence of cross-linking agent, the average PGE fiber diameter increased from 347 +/- 103 nm to 999 +/- 123 nm upon wetting as measured by scanning electron microscopy. Rat bone marrow stromal cells (rBMSC) were used paradigmatically to study the 3-D cell culture properties of PGE scaffolds. Consistent with the observed properties of the individual fibers, PGE scaffolds initially swelled in aqueous culture medium, however rBMSC seeded PGE scaffolds contracted to less than 50% of original size. Time course histological analysis demonstrated uniform seeding of rBMSC into PGE scaffolds and complete cell penetration into the fibrous architecture over 4 weeks of in vitro culture. PMID- 17281591 TI - Nanofunctionalisation for the treatment of peripheral nervous system injuries. AB - A construct based on the electrostatic layer-by-layer self assembly technique has been fabricated, to be used as a tailored device to encourage nerve regeneration. A multilayered nanocoating composed by three precursor bilayers of cationic and anionic polyelectrolytes followed by bilayers of poly-D-lysine (PDL) and antibody specific to Transforming Growth Factor beta1 (anti-TGF-beta1) has been deposited on HYAFF 11. Initially the assembly process has been monitored by quartz crystal microbalance (QCM) in order to select the optimal working conditions for nanocoating deposition. Structural studies of the resulting multilayers confirmed stepwise deposition of anti-TGF-beta1 with an average layer thickness of 2.6 nm and an average layer mass of 117 ng. Atomic Force Microscopy has been used to characterize multilayer uniformity. Finally, the immunological activity of the multilayered structure has been assessed. The results show that anti-TGF-beta1 can be included in its active form in a predetermined multilayered structure onto HYAFF11 with quantitative control of layer thickness and weight, providing a high potential tool in tissue engineering. PMID- 17281593 TI - Investigating testing elasticity of equivalent material for human skin. AB - To the elasticity specificity of equivalent materials with human skin's nature, the static-load pressing method for testing the elastic nature of the equivalent material for human skin is approached in this paper, and the experimental set for the testing process is designed. And it is very important and useful to biomedicine science and engineering that evaluating correctly the mechanical property of the equivalent materials with human skin's nature. PMID- 17281594 TI - Wireless head cap for EOG and facial EMG measurements. AB - A head cap made of fabric for measuring EOG and facial EMG signals is presented. Reusable and easy to use electrodes, embroidered of silver coated thread, are integrated into the cap. A two-way wireless data transmission link operating at license free 2.4 GHz frequency band is used for transferring the 16-bit measurement data, sampled with 1 kHz frequency from six channels at maximum, to the receiver device connected to a PC. Tailored PC software is used for displaying the signals and controlling the measurement parameters. The measurement system is intended for recording facial expressions during human emotion studies but it can also be utilized in computer user interface control. The paper shows preliminary results from EOG and facial EMG measurements. PMID- 17281595 TI - Accurate determination of respiratory rhythm and pulse rate using an under-pillow sensor based on wavelet transformation. AB - A real-time noninvasive and unconstrained method is proposed to determine the respiratory rhythm and pulse rate with an under-pillow sensor during sleep. The sensor is composed of two fluid-filled polyvinyl tubes set in parallel and sandwiched between two acrylic plates. One end of each tube is hermetically sealed, and the other end is connected to one of two pressure sensors. Inner pressure in each tube therefore changes in accordance with respiratory motion and cardiac beating. By employing the a trous algorithm of wavelet transformation (WT), the respiratory and cardiac cycle can be discriminated from the pressure waveforms. The respiratory rhythm was obtained from the WT 26> scale approximation, and the pulse rate from the sum of WT 24and 25scale details without WT reconstruction after soft-threshold denoising. The algorithm's latency can be set to be minimal and the respiratory rhythm and pulse rate were estimated directly from the extracted respiration and pulse waveforms, respectively. This method has been tested with a total of about 25 h data collected from 13 subjects. By comparing the detection results with those of reference data, the average pulse rate detection sensitivity and positive predictivity were 99.17% and 98.53%, and the respiratory rhythm detection sensitivity and positive predictivity were 95.63% and 95.42%. PMID- 17281596 TI - A Non-invasive detection of lung cancer combined virtual gas sensors array with imaging recognition technique. AB - In this paper, we propose a non-invasive detection method of lung cancer combined with a sort of virtual SAW gas sensors array and imaging recognition method. A patient's breath goes through an electronic nose with solid phase micro extraction (SPME) and capillary column for pre-concentration and separation of volatile organic compounds (VOCs) respectively, a pair of SAW sensors one coated with a thin Poly-isobutylene (PIB) film is connected to the output of capillary column port for chemical compounds detection. A lung cancer tissues' culture medium study is also proposed for pathology validation. 11 VOCs which are considered as the biomarkers of lung cancer can be detected qualitatively and quantitatively. Finally these 11 VOCs are used to diagnose lung cancer patients in Run Run Shaw hospital by our e-nose with an improved artificial neural network (ANN) algorithm combined with imaging method for pattern recognition. PMID- 17281597 TI - Cuff-less and noninvasive measurements of arterial blood pressure by pulse transit time. AB - The current blood pressure (BP) measurement devices are mostly built on the principle of auscultation, oscillometry or tonometry, all of which use an inflatable cuff to occlude or unload the artery. The need of a cuff in these devices limits the further reduction in size and power consumption, and restricts the frequency and ease of their usage. Therefore, this study aims to develop a cuff-less and noninvasive technique for measuring BP by pulse transit time. The technique was evaluated on 85 subjects, aged 57+/-29 yrs., including 36 males and 39 hypertensives, over an average period of 6.4 wks. A total of 999 pairs of systolic BP (SBP) and diastolic BP (DBP) estimations were made. The average of BP readings reported by an experienced registered nurse and those obtained from a clinically approved automatic BP meter was used as reference. It is found that the estimated SBP and DBP differed from the reference BP by 0.6+/-9.8mmHg and 0.9+/-5.6mmHg respectively. When compared to the AAMI requirement (5+/-8mmHg for both SBP and DBP estimation), the results suggest that the cuff-less technology has great potential to be developed into wearable devices that are useful in self BP monitoring for home healthcare and eventually in clinical diagnosis. PMID- 17281598 TI - Common mode noise cancellation for electrically non-contact ECG measurement system on a chair. AB - Electrically non-contact ECG measurement system on a chair can be applied to a number of various fields for continuous health monitoring in daily life. However, the body is floated electrically for this system due to the capacitive electrodes and the floated body is very sensitive to the external noises or motion artifacts which affect the measurement system as the common mode noise. In this paper, the Driven-Seat-Ground circuit similar to the Driven-Right-Leg circuit is proposed to reduce the common mode noise. The analysis of this equivalent circuit is performed and the output signal waveforms are compared between with Driven-Seat Ground and with capacitive ground. As the results, the Driven-Seat-Ground circuit improves significantly the properties of the fully capacitive ECG measurement system as the negative feedback. PMID- 17281599 TI - Estimation of respiratory rate and heart rate during treadmill tests using acoustic sensor. AB - The objective was to test the robustness of an acoustic method to estimate respiratory rates (RR) during treadmill test. The accuracy was assessed by the comparison with simultaneous estimates from a capnograph, using as a common reference a pneumotachometer. Eight subjects without any pulmonary disease were enrolled. Tracheal sounds were acquired using a contact piezoelectric sensor placed on the subject's throat and analyzed using a combined investigation of the sound envelope and frequency content. The capnograph and pneumotachometer were coupled to a face mask worn by the subjects. There was a strong linear correlation between all three methods (r2ranged from 0.8 to 0.87), and the SEE ranged from 1.97 to 2.36. As a conclusion, the accuracy of the respiratory rate estimated from tracheal sounds on adult subjects during treadmill stress test was comparable to the accuracy of a commercial capnograph. The heart rate (HR) estimates can also be derived from carotid pulse using the same single sensor placed on the subject's throat. Compared to the pulse oximeter the results show an agreement of acoustic method with r2=0.76 and SEE = 3.51. PMID- 17281600 TI - Improved estimation of human cortical activity and connectivity with the multimodal integration of neuroelectric and hemodynamic data. AB - In the last decade, the possibility to noninvasively estimate cortical activity and connectivity has been highlighted by the application of the techniques known as high resolution EEG. These techniques include a subject's multi-compartment head model (scalp, skull, dura mater, cortex) constructed from individual magnetic resonance images, multi-dipole source model, and regularized linear inverse source estimates of cortical current density. More recently, it has proved as the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI improves dramatically the estimates of cortical activity and connectivity. Here, we present some applications of such estimation in two set of high resolution EEG and fMRI data, related to the motor (finger tapping) and cognitive (Stroop) tasks. We observed that the proposed technology was able to unveil the direction of the information flow between the cortical regions of interest. PMID- 17281601 TI - A spectral clustering approach to fMRI activation detection. AB - Conventional clustering methods for fMRI activation detection implicitly assume that data scatter in clusters with certain shapes. But this assumption is inconsistent with the general reality in fMRI data, and will consequently achieve detection results with higher false alarm rate. To solve this problem, we propose an alternative clustering method, namely spectral cluster analysis (SCA), which uses eigenvectors of a matrix derived from the dataset to cluster the wavelet coefficients extracted from the fMRI time series. Experimental results demonstrate reliability and flexibility of this new fMRI clustering approach. PMID- 17281602 TI - Nonlinear Canonical Correlation Analysis of fMRI Signals Using HDR Models. AB - A nonlinear canonical correlation analysis (CCA) for detecting neural activation in fMRI data is proposed in this paper. We use the BOLD response based on the HDR models with various parameters as reference signals. Instead of characterizing the relationship between the paradigm and time series using the oversimplified linear model, we employ the kernel trick that maps the intensities of the voxels within a small cubic at each time point into a high-dimensional kernel space, where the linear combinations correspond to nonlinear ones in the original space. The experimental results show that the proposed nonlinear CCA can improve the detection performance of traditional linear CCA. PMID- 17281603 TI - Application of near-infrared spectroscopy to measuring of attractiveness of opposite-sex faces. AB - Brain imaging technology employing near-infrared spectroscopy (NIRS) has great potential in various applications to daily life, by virtue of offering handy equipment and an easy measurement method. In this paper, we propose a novel application of NIRS to evaluation of feeling. As compared with an electroencephalogram, the NIRS offers easier attachment of probes on the scalp, because it does not require any paste. As compared with the magnetic resonance image system, the NIRS can detect hemodynamic response by much smaller equipment. To examine the suitability of NIRS for evaluation of feeling, we measured hemodynamic responses in the left anterior frontal cortex, which we then correlated with reported assessments of facial attractiveness. Oxy-hemoglobin in the area increased when the subjects evaluated the faces as unattractive, and the amount of increase measured in each trial was proportional to the degree of unattractiveness. This result indicates the availability of NIRS to real-time evaluation of feeling. PMID- 17281604 TI - CRLS-PCA based independent component analysis for fMRI study. AB - Data reduction through conventional principal component analysis is impractical for temporal independent component analysis (tICA) on fMRI data, since the data covariance matrix is too huge to be manipulated. It is also computationally intensive for spatial ICA (sICA) on long time fMRI scans. To solve this problem, a cascade recursive least squared networks based PCA (CRLS-PCA) was used to reduce the fMRI data in this paper. Without the need to compute data covariance matrix CRLS-PCA can extract arbitrary number of PCs directly from the original data, which simultaneously saves time for data reduction. Experiment results were given to evaluate the performance of CRLS-PCA based tICA and sICA in fMRI study. PMID- 17281605 TI - Model-Based receptor quantization analysis for PET parametric imaging. AB - Dynamic PET (positron emission tomography) imaging technique allows image-wide quantification of physiologic and biochemical parameters. Compartment modeling is the most popular approach for receptor binding studies. However, current compartment-model based methods often either require the accurate arterial blood measurements as the input function or assume the existence of a reference region. To obviate the need for the input function or a reference region, in this paper, we propose to estimate the input function and the kinetic parameters simultaneously. The initial estimate of the input functions is obtained by the analysis of space intersections. Then both the input function and the receptor parameters, thus the underlying distribution volume (DV) parametric image, are estimated iteratively. The performance of the proposed scheme is examined by both simulations and real brain PET data in obtaining the underlying parametric images. PMID- 17281606 TI - The decomposition of surface EMG signals based on blind source separation of convolved mixtures. AB - The decomposition of surface EMG signals can provide valuable information about the recruitment and firing of motor units from surface EMG recordings. According to the physiologic characteristic of the surface EMG signals generation, a method of the decomposition of SEMG signals based on the technique of convolved mixing blind source separation was proposed. Using simulated SEMG signals, the performance of the decomposition algorithm was analyzed and compared with that of the decomposition technique adopting Independent Component Analysis (ICA). The experiment results show that the proposed method could decompose SEMG signals effectively, and it's performance is better than the ICA decomposition method, no matter for the simulated or recorded SEMG signals. PMID- 17281607 TI - Improved method for fetal heart rate monitoring. AB - The fetal ECG can be detected in the recorded abdominal signals. A new procedure to compute the fetal heart rate (FHR) is proposed. The abdominal signal is first preprocessed in order to remove the baseline and the uterine contractions. Then the ECG of the mother (MECG) is removed using coherent averaging and optimizing the averaged MECG template. The channels containing the clearest fetal ECG signal (FECG) are identified by the autocorrelation function. The FECG is enhanced by the cross correlation between the two channels that show the strongest FECG. This enhancement is possible since the residual noise in the abdominal signal after removal of baseline, uterine contractions and maternal ECG is not correlated among the channels. The fetal R-Peaks are then detected and the FHR is computed. The obtained FHR is further corrected, using the information about the MECG and about the FECG. PMID- 17281609 TI - A method based on wavelet transform to reduce 1/f noise. AB - In this paper a method for reducing white noise and 1/f noise is investigated. Instead of modifying the hardware design of SQUID detector, we seek to reduce 1/f noise by the wavelet transform approach, which statistical characteristics in the wavelet domain are used. By applying this method to the simulated noise MCG signal, we demonstrate that both the white noise and the 1/f noise can be significantly reduced. PMID- 17281608 TI - Double spectral theorem and two type magnitude-squared coherence functions. AB - Studying frequency domain representation for the coherence between two signals is an important basic theoretical problem in the fundamental theories of signal processing. However, the old magnitude-squared coherence function (OMSCF) has been proved identical to 1, so that to cannot be used to extract any coherence information. Here, we will prove a core theorem in frequency domain coherence theories in signal processing, called as the double spectral theorem (DST). Based on the theorem, we presented the two types of new magnitude-squared coherence functions (MSCFs), called as the same type magnitude-squared coherence function (SMSCF) and the difference magnitude-squared coherence function (DMSCF) respectively, which were mathematically derived from DST and the conditions that they are equal to 1 or 0 can be theoretically derived from DST. Here, we further demonstrated that SMSCF and DMSCF could be used to exactly extract the coherence between two signals by each component. PMID- 17281610 TI - Analysis of time-varying coherence of EEG during face recognition based on harmonic transform. AB - Distinct cortical activity during face recognition was reported by a number of studies. Classical coherence analysis reflects the synchronization between two random processes in certain frequency under the assumption that the signals are stationary. In EEG study, the coherence analysis is mainly used to analyze the coupling and drive-response relation about the brain activities in different regions. Classical coherence analysis can extract the rhythmic consistency of the EEG activities in different regains. However, classical coherence can not extract the transient synchrony characteristics of brain activities. In order to track the spatial-temporal characteristics of EEG activities during cognitive conception, the time-varying coherence analysis is proposed. The EEG of 10 participants was recorded during recognition of familiar and unfamiliar faces, experiment results show that there is obvious difference about the model of information communication between temporal region and other brain regions in alpha rhythm during cognitive processing. PMID- 17281611 TI - EMG signal classification for myoelectric teleoperating a dexterous robot hand. AB - This paper details a strategy of discriminating finger motions using surface electromyography (EMG) signals, which could be applied to teleoperating a dexterous robot hand or controlling the advanced multi-fingered myoelectric prosthesis for hand amputees. Finger motions discrimination is the key problem in this study. Thus the emphasis is put on myoelectric signal processing approaches in this paper. The EMG signal classification system was established based on the surface EMG signals from the subject's forearm. Four pairs of electrodes were attached on the subjects to acquire the signals during six types of finger motions, i.e. thumb extension, thumb flexion, index finger extension, index finger flexion, middle finger extension, and middle finger flexion. In order to distinguish these finger motions. A combination of autoregressive (AR) model and an Artificial Neural Network (ANN) was used in the system. The discrimination procedure consists of two steps. Firstly, the AR model is used to preprocess the surface EMG signals to reduce the scale of the data. These data will be imported into the myoelectric pattern classifier. Secondly the coefficients of AR model are imported into the ANN to identify the finger motions. The experimental results show that the discrimination system works with satisfaction. PMID- 17281612 TI - The investigation on sEMG of lower extremity when a slip occurs in level walking. AB - The purpose of the present study was to determine the relationship between the surface electromyography (sEMG) variables and slip events using principal component analysis (PCA). Ten healthy young adults were required to walk on the oily surface on a self-selected comfortable pace. The sEMG signals of lower extremity muscles were recorded and analyzed, while kinematics data was recorded to assist slip definitions. When ten variables (seven in time domain and three in frequency domain) were considered in the PCA, the results indicated that 1) three most important principal components could explain more than 85% of the variation in the entire data set; 2) some variables should be especially noticed such as muscle power, the mean frequency, the median frequency and the amplitude amount exceeding the mean value. PMID- 17281613 TI - Extracting ERP by combination of subspace method and lift wavelet transform. AB - Event Related Potentials (ERP) recorded from the scalp include various noises. The main source of the noise is the spontaneous brain activity and it is called the background Electroencephalography (EEG). Because EEG is highly colored, we wouldn't effectively remove EEG noise by wavelet transform. This paper proposed a new approach that combined the subspace method and lift wavelet transform in order to reduce the number of trials required for the extraction of the brain Event Related Potentials. First, the signal subspace is estimated by applying the singular value decomposition (SVD). Orthonormal projecting the raw data onto the estimated signal subspace can obtain a pre-denoised signal and it whitened the colored noise. Next, the ERPs are extracted by lift wavelet construction of the enhanced version. Simulation results show that the combination of both two methods provides much better capability than each of them separately. PMID- 17281615 TI - De-Noising of ECG signal using translation- invariant wavelet de-noising method with improved thresholding. AB - The electrocardiogram (ECG) signal may mix various kinds of noises while gathering and recording. Wavelet thresholding de-noising method based on discrete wavelet transform (DWT) proposed by Donoho et al. is often used in de-noising of ECG signal. According to the defects of Donoho's method in de-noising of ECG signal, this paper proposes an improved thresholding de-noising method based on Donoho's method. The advantage of the improved de-noising method is that it may not only remain the geometrical characteristics of the original ECG signal and keep the amplitudes of various ECG waveforms efficiently, but also suppress impulsive noise to some extent. Furthermore, the traditional wavelet thresholding de-noising method causes Pseudo-Gibbs phenomena in Q and S waves of ECG signal due to DWT. In order to suppress Pseudo-Gibbs phenomena in Q and S waves, a new de-noising method combining above improved thresholding with the translation invariant wavelet transform is proposed in this paper. The experimental results indicate that the proposed methods in the paper are better than traditional wavelet thresholding de-noising methods in aspects of remaining geometrical characteristics of ECG signal and the signal-to-noise ratio (SNR). PMID- 17281614 TI - Study on the spatial variability and the sampling scheme of soil nutrients in the field based on GPS and GIS. AB - With the introduction of GPS and GIS, the spatial variability of soil properties was measured and analyzed using traditional statistics method and geo-statistics. 63 sampling points were measured on a 50m grid in the soil surface (0~20cm) of a 13.3 hectare winter-wheat field and were positioned by the GPS receiver. The results show that all soil nutrients are normal distribution and represent moderate spatial variability. The organic matter, total-N, NH 4-N, and available K have strong spatial correlation, while the available P exhibits moderate spatial variability, and the range of soil properties is 265.8-349.7m. The standard errors of the 63 sampling points were respectively computed in kriging interpolation method. The results indicate that the errors increased with the decrease of the sampling points. The 50m X 100m and 100m X 100m sampling schemes were recommended for their higher precision and economical efficiency. Thus, they are preferable in the large-scale sampling. PMID- 17281616 TI - Incorporating BSS to epileptic seizure predictability measure from scalp EEG. AB - Epileptic seizure prediction has been explored by many researchers for decades. Most of the methods are based on the evaluation of the chaotic behavior of intracranial electroencephalographic (EEG) recordings. Here, a novel approach has been developed to predict the dynamical changes of the brain from the scalp EEG signals. Blind source separation (BSS) has been successfully used to separate the EEG signals into their constitute components including the seizure sources. Then the chaotic behavior was evaluated by measuring the short-term largest Lyapunov exponent (STLmax). The simultaneous intracranial and scalp EEG recordings were used to compare our approach with the traditional method using intracranial recordings. Similar prediction results were obtained from the scalp and intracranial recordings. Also different BSS algorithms were applied to compare their performance of source separation. PMID- 17281617 TI - Estimation of propagation velocity of gastric electrical activity using LMSTDE. AB - The least mean square time delay estimate (LMSTDE) algorithm is independent of the prior knowledge of signals and noises. Under the LMS criterion, the best estimate is acquired by automatic adjusting related parameters. In this paper, we applied LMSTDE to estimate the propagation velocities of four-channel gastric myoelectrical recordings that were obtained from implanted gastric serosal electrodes in three gastroparetic patients. The performance of the method was investigated using computer simulations. The results of this paper showed that the average velocities in gastroparetic patients are slower than in normal subjects. The propagation of gastric slow wave is along the greater curvature from upper 1/3 of the corpus toward the pylorus but the variability of the propagation velocity does not increase monotonously. PMID- 17281618 TI - Study on EEG source localization in frequency domain. AB - This article deals with a new approach based on predominant frequency that combines EEG source localization methods with standard frequency analysis of multi-electrode EEGs. First, we describe the theoretical methodology of the frequency domain source localization. Then, this new application is used as signal-processing technique on simulating EEG recordings obtained from both single dipole model and double dipole model. Finally, we show that the obtained results constitute a promising methodology to study the cerebral electrical activity. PMID- 17281619 TI - Phoneme classification for speech synthesiser using differential EMG signals between muscles. AB - This paper proposes the use of differential electromyography (EMG) signals between muscles for phoneme classification, with which a Japanese speech synthesiser system can be constructed using fewer electrodes. In distinction from traditional methods using differential EMG signals between bipolar electrodes on the same muscle, an EMG signal is derived as differential between monopolar signals on two different muscles in the proposed method. Then, frequency-based feature patterns are extracted with filter banks, and classification of phonemes is realized by using a probabilistic neural network, which combines feature reduction and pattern classification processes in a single network structure. Experimental results show that the proposed method can achieve considerably high classification performance with fewer electrodes. PMID- 17281620 TI - Electrical stimulation of isolated rabbit retina. AB - Several research groups in the world are trying to restore useful vision for the patients of degenerate retina, such as retinitis pigmentosa (RP) and age related macular degeneration (ARMD) with retinal prosthesis. Recently Korean consortium launched for developing retinal prosthesis and as part of Korean retinal prosthesis project we provide preliminary experimental results regarding voltage parameters for the stimulation of isolated retina. Voltage stimulus was delivered via one of the channel of microelectrode array (MEA) and ganglion cell activities were recorded with remained 59 channels. We changed the voltage amplitude from 0.5 V to 3 V, which showed that threshold level for reliable ganglion cell response was 1.5 V. The calculated threshold for charge densities was 2123 muC/cm2 and charge delivery was 15 nC/phase. When we changed the stimulus duration from 100 mus to 1200 mus with fixed voltage of 2 V, the threshold level was 300 mus. The calculated charge densities and charge delivery were 1698 muC/cm2 and 12 nC/phase, respectively. Even after the block of on-bipolar cell with L-(1)-2-amino-4-phosphonobutyric acid (APB), electrical stimulus evoked ganglion cell activities. PMID- 17281621 TI - Development of the EEG measurement technique under exercising. AB - Our purpose of this research is a development of the method that detects EEG of an athlete under exercising. If EEG under exercising can be measured, we can assess the mental condition of the athlete. Usually, EEG is measured in the shield room, and a subject is required rest in bed while measurement. And it is said that measuring EEG under exercising is difficult. In this paper, we will discus about our new measuring method that can detect EEG under exercising by using independent component analysis. Five normal subjects were tested with our method, and EEG without artifact was able to measured. So, we think our new method will be useful for the research of mental condition of the athlete. PMID- 17281622 TI - Feature attraction and classification of mental EEG using approximate entropy. AB - The approximate entropy (ApEn), which is a new statistical method to measure the complexity of sequences, was introduced in this paper. First, the EOG artifact was removed from the EEG using the method of independent component analysis (ICA). Then ApEn was used to analyze the mental EEG signals to extract the features for pattern identification and task classification. The simulations showed that the classification accuracy is high and the proposed methods are effective. PMID- 17281623 TI - Study of the surface Laplacian SNR. AB - The surface Laplacian involves the second derivative of the potential. It will give different and perhaps more localized information concerning the sources that give rise to the surface potential distribution. In this article we study the SNR of the surface Laplacian, and figure out the measuring possibility of the surface Laplacian of some bioelectrical signals that never been mentioned by others. PMID- 17281624 TI - Adaptive spatio-temporal filtration of bioelectrical signals. AB - In this paper we show how independent component analysis (ICA) algorithms can be used to perform spatio-temporal filtration of electromyographic (EMG) and electrocardiographic (ECG) signals. The technique was used to decompose the EMG signals into motor unit action potential (MUAP) trains. From the 88 outputs of the adaptive spatio-temporal filtration, three groups of different MUAP train patterns were found. The technique was also used to obtain a fetus' ECG and showed better result compared to using ICA. PMID- 17281625 TI - Real-time access of magnetoencephalographic / -cardiographic data: technical realization & application to online fetal heart rate recording. AB - Current standard magnetoencephalographic and -cardiographic systems do not allow real-time access to the measured data. We developed a software solution for real time access and used it to create an online fetal heart rate monitor. PMID- 17281626 TI - Robustness of mutual information to inter-subject variability for automatic artefact removal from EEG. AB - The externally recorded electroencephalogram (EEG) is contaminated with signals that do not originate from the brain, collectively known as artefacts. Thus, EEG signals must be cleaned prior to any further analysis. In particular, if the EEG is to be used in online applications such as Brain- Computer Interfaces (BCIs) the removal of artefacts must be performed in an automatic manner. This paper investigates the robustness of Mutual Information based features to inter-subject variability for use in an automatic artefact removal system. The system is based on the separation of EEG recordings into independent components using a temporal ICA method, RADICAL, and the utilisation of a Support Vector Machine for classification of the components into EEG and artefact signals. High accuracy and robustness to inter-subject variability is achieved. PMID- 17281627 TI - Study of change blindness EEG synchronisation using wavelet coherence analysis. AB - 'Change blindness' is the failure to detect substantial changes in the visual field that normally would be noticed easily. This effect is of interest as by making comparisons with change detection, it may be informative of the brain activity that occurs during visual awareness. This paper proposes a wavelet coherence analysis for measuring the degree of synchronisation of multi-channel electroencephalograph (EEG) signals during experiments of change detection and change blindness in picture pairs presented between blank inter-stimulus intervals. The magnitude of wavelet coherence is found to exhibit significant differences between the hit and miss visual states. The ANOVA test verified the statistical significance of coherence differences (p less than 0.01) between hits (change detection) and misses (change blindness) in cross-channel synchronization. PMID- 17281628 TI - Computerized classification of normal and abnormal lung sounds by multivariate linear autoregressive model. AB - This work proposes multichannel acquisition of lung sounds by a microphone array, feature extraction by a multivariate AR (MAR) model, dimensionality reduction of the feature vectors (FV) by SVD and PCA and, their classification by a supervised neural network. A microphone array of 25 sensors was attached on the thoracic surface of the subjects, who were breathing at 1.5 L/sec. The supervised neural network used the backpropagation learning algorithm based on the Levenberg Marquardt rule. Figures of merit for the classification task by the neural net include the percentage of correct classification during training, testing and validation phases as well as sensitivity, specificity and performance. MAR in combination with PCA provided the best average percentage of correct classification with acoustic information not seen by the neural network during the training phase (87.68%). The results state the advantages of a microphone array for the classification of normal and abnormal acoustic pulmonary information in diffuse interstitial pneumonia and for this goal, the authors assume that not only the crackles and their number indicates the severity of the disease, but the basal respiratory signal could be also affected. PMID- 17281629 TI - Analysis for brain activities during operations using measured EEG. AB - EEG (electroencephalogram) analysis is one of the most familiar methods. The goal of this study is to develop the integrated EEG analysis software. In some cases, temporary or permanent occlusion of the arteries, which participates the cerebral blood flow, is needed during surgery. It is important to monitor the brain condition to prevent from a sequel. In this study, we propose moving average type neural networks (MANN) are applied to analyze the EEG, too. In this method, measured EEG is divided into overlapped period of 30 seconds. A MANN is trained to predict EEG by using of previous 5 samples in each period. After the training, connection weights of each MANN are compared by inner product to evaluate changes of brain condition. According to the result of analysis of a clinical data, the usefulness of the MANN analysis and DR(deviation ratio) analysis was confirmed. PMID- 17281630 TI - Comparison of five different classifiers for classification of mental tasks. AB - In this work we consider classification of mental tasks from EEG signal by using five different classifiers. These include Neural Network, Bayesian graphical network, Bayesian quadratic classifier, Hidden Markov Model and Fisher linear classifier. The experimental results are compared to each other. The Bayesian network appears to have comparable accuracy with the best classifier of the five but the classification time for it is more than others. PMID- 17281631 TI - Extraction of arterial blood pressure signal from intraluminal impedance signals. AB - Multichannel intraluminal procedure provides information about the esophagus status, reflux occurrence, and clearance mechanism. The study of the impedance signals has been concentrated on the study of reflux patterns and clearance mechanisms. However, there are a number of sources that results in the variations seen in impedance signal. These sources include esophageal characteristic, reflux occurrence, catheter movement, arterial blood pressure and respiration signal. This paper presents the use of the blind signal separation to extract the arterial blood pressure signal from the impedance signals. The extracted signal is further processed to get clean arterial blood pressure signal. The respiration signal can also be extracted in a similar approach. PMID- 17281632 TI - Automatic detection of sleep stages in neonatal EEG using the structural time profiles. AB - The new method for automatic sleep stages detection in neonatal EEG was developed. The procedure is based on processing of time profiles computed by adaptive segmentation and subsequent classification of signal graphoelements. The time profiles, functions of the class membership in the course of time, reflect the dynamic EEG structure and may be used for indication of changes in the neonatal sleep stages. PMID- 17281633 TI - Removing eye movement and power line artifacts from the EEG based on ICA. AB - The presence of different artifacts has long been a problem for the analysis and interpretation of electroencephalographic (EEG) recordings. Independent Component Analysis (ICA) is a technique for Blind Source Separation (BSS) and has been used to remove biomedical artifacts. In order to subtract the power line noise effectively and robustly, we use two additional channels of artificial power line signals and the EEG recordings to form a new data set as the input of ICA, and the data were separated into independent components based on the extended ICA method, and the EEG signal was reconstructed by excluding those components related to eye movement and line artifacts. Experiment results indicated the method is effective and satisfying. PMID- 17281634 TI - Different plantar interface effects on dynamics of the lower limb. AB - The moments acting on the lower limb joints influence the life of the arthrosis. These loads may depend on the footwear and action style. The footwear factor was studied with three-dimensional gait measure system. Five young women in their 20s, wear 7 cm high-heeled shoes and sneakers, and walked in 10 m gait laboratory walkway. Inversed dynamics was used to analysis the torques at the ankle, knee and hip. Results showed that peak adduction moments at the knee and ankle increased and flexion/extension moments at hip increased with high-heel shoes compared with the sneakers. The high-heeled shoes result in greater load in lower limb joints especial to the knee and hip. PMID- 17281635 TI - New method for estimation of mobile location based on signal attenuation and hata model signal prediction. AB - This paper proposes a new algorithm, based on the received signal strength, for mobile location estimation. The algorithm, considering path loss and shadowing for the channel, estimates the distance between the mobile and the home and neighboring base stations, and computes an improved form of the weighted gravity center of the above estimated distances. Simulation results show that the mean error estimation of the mobile location obtained by the proposed algorithm is much smaller than that of the cell-ID, and it is at least 15% better than that of the weighted gravity center method. PMID- 17281636 TI - Web-based integrated alarm monitoring system in the ICU. AB - A web-based monitoring system for the alarm of equipment has developed for the conventional environment of Intensive Care Unit (ICU). The system communicates with equipment using Data Collection Interface (DCI) that converts the protocol of the output of equipment from RS-232C to TCP/IP. The system creates a web document that can be referred from any internet-connected personal computer in the hospital. Using the system, a staff can easily monitor the state of the patient and the equipment. If the system is installed in the ICU, monitoring and management for the equipment will be highly improved. PMID- 17281637 TI - The development and evaluation of new neck coil for GE MR system. AB - Due to the MRI signal is much low, the improvement of image quality becomes the important goals for MRI equipment R&D. The RF coil is one of the most important factors in detecting the MRI signal. A new neck coil is developed with four channels phase array design and evaluated. Compared with original coil, the image signal to noise ratio (SNR) and uniformity of new neck coil are improved evidently. PMID- 17281638 TI - The practice of new framework of medical equipment service management. AB - Due to increasing integration and reliability of modern medical devices, based on the situation of China, the new framework for medical equipment management must be explored. The new system involves not only in-house and manufacturer, but also the third parties. Compared with the original concept, the 6-year-long exploration of the partnership with third parties and manufacturers has contributed to achieving a "win-win" situation. PMID- 17281640 TI - Development and transformation of working mode in clinical engineering department. AB - This paper starts with analyzing the development and history of clinical engineering in China, analyzing the macro-environment of clinical engineering and summarizing the practice experiences of Chinese and foreign CE department. It puts forward a new idea that clinical engineering working mode should be changed from "working around repairing" to "working around equipment quality control and safety management". PMID- 17281639 TI - Digital geometry processing applied in customized medical implant design. AB - Standard medical implants are used in most implantation cases, but in some special cases, only those implants conforming to individual patient's skeletal morphology can serve the purpose. This paper proposes a new approach to design and fabricate customized exact-fit medical implants. With a real surgical case as the example, technical design details are presented; and two algorithms are given respectively for segmentation based on object features and triangular mesh defragmentation. PMID- 17281641 TI - An apparatus and method to characterize causes of positional plagiocephaly. AB - Positional plagiocephaly (misshapen head in infants) has increased dramatically in the United States since the beginning of the Back to Sleep program in 1992. In order to understand the increase due to repositioning from prone to supine position for sleep, we developed a home-based monitoring system to discern state of sleep and re-positioning frequency in infants. The portable system allows real time logging of sleep position and patterns by a simplified sleep algorithm and association of sleep head position and movement which are time-stamped for correlation. Preliminary correlatory results suggest that plagiocephalic infants experience greater periods of rapid-eye-movement (REM) sleep than controls and show more narrow range of motion during sleep. PMID- 17281642 TI - Research on linguistic concept creation method applied to environmental comfort sensors in health smart home. AB - We endeavor to provide a novel tool to evaluate environmental comfort level in Health Smart Home (HSH). HSH is regarded a good alternative for the independent life of elders and people with disability. Numerous intelligent devices, installed within a home environment, can provide the resident with continuous monitoring and comfortable environment. In this paper, a novel method of evaluating environmental comfort level is provided. An intelligent sensor is a fuzzy comfort sensor that can measure and fusion the environmental parameters. Based upon the results, it will further give a linguistic description about the environmental comfort level, in the manner of an expert system. The core of the sensor is multi-parameter information fusion. Similar to human behavior, the sensor makes all the evaluation about the surrounding environment's comfort level based on the symbolic measurement theory. We applied chart representation theory in multivariate analysis in the biomedical engineering field to complete the human comfortable sensor's linguistic concept creation. We achieved better performance when using this method to complete multi-parameter fusion and fuzziness. It is our belief that this method can be used in both biology intelligent sensing and many other areas, where the quantitative and qualitative information transform is needed. PMID- 17281643 TI - The study on brain paralysis ultrasonic therapy instrument simulating dolphin. AB - To cure brain paralysis this paper has briefly summarized the rudimentary knowledge of the ultrasonic therapy, and briefly introduced the methods of dolphin ultrasonic therapy, through the research of the dolphin ultrasonic therapy, the ultrasonic frequency chart wave band which is more efficient to the therapy of brain paralysis is measured, and one method of simulated dolphin therapy mechanism is found. Finally, one of the ultrasonic therapy instruments against brain paralysis is developed. PMID- 17281644 TI - Development of an imageless navigation system for total knee arthroplasty. AB - Will being an important part of modern operation room, in recent years computer aided technology has become more and more integrated in different surgical procedures, such as brain, spine, ENT, hip, knee etc. A vast number of papers have been published on computer assisted knee surgery recently with inspiring clinical results, such as more precise alignment and more minimally invasive. An innovative and universal image-free computer-aided TKA system is introduced in this article. Through dynamic, detailed navigation screens, instruments are accurately depicted in relation to a patient's anatomy to aid femoral and tibial osteotomy, so intramedullary hole drilling and ankle clamp attaching have been avoided. Undermentioned functions are also realized: base kinematics, postoperative kinematics, soft tissue balancing. PMID- 17281645 TI - Development of a Grid-based statistical potential for protein structure prediction. AB - A key component in protein structure prediction is the development of potentials that can discriminate native or near native structures from the wrong ones. Most previously developed statistical potentials are based on the preferred distances between any pair of residues. Here we explore the possible angle dependence between pairs of residues in addition to their distance dependence. For simplicity, we used a grid based partition of the space and analyzed relative geometric propensity between protein residue pairs. One thousand and nine non redundant protein structures are studied in this paper. We have attached a local coordinate system to each amino acid, and spatial distributions of its nearby residues are investigated. Within the same distance range, there are clear differences in various grids. We have further developed a grid-based statistical potential, which incorporates both the distance dependence and angle dependence using a quasi-chemical approximation. The potential is tested against 32 decoy sets, and in 25 cases the native structure has the best score. This performance is comparable and in two cases better than best performance from previously developed distance-dependent statistical potentials on residue and atom level. PMID- 17281646 TI - A novel neuron data model with domain specific query language. AB - A novel neuron data model with a neuron domain specific query language is proposed in this paper. It is inspired by the project NeuronBank [14]. This data model is composed of five components: neuron data structure, constraints, operations, domain-specific query language (NeuroQL), and controlled vocabulary. It can capture and enforce more domain semantics than traditional data models, such as attributes of attributes and source information. It also enables users to model their special interests and constraints on any entity or its attribute in the data model. NeuroQL defines a list of queries in neuroscience terms, and can be easily extended. PMID- 17281647 TI - Novel method for missing value estimation in gene expression profile based on support vector regression. AB - Gene expression profile is a kind of useful biological resource in recent years. The original data is usually in the form of large matrix with missing values in it. Missing value estimation method is in active demand as many downstream analysis methods suffered from the missing values. Several methods dealing with this problem have been reported (proposed) recently. We proposed a novel missing value estimation method based on Support Vector Regression. Various parameter sets and input coding schemes were employed, and the performance of our method was evaluated over different data sets by comparing with other existing methods. Results show that our method is comparative, if not better than, those previous methods. PMID- 17281648 TI - Phosphorylation site prediction with a modified k-nearest neighbor algorithm and BLOSUM62 matrix. AB - Phosphorylation is one of the most important post-translational modifications for eukaryotic proteins. Experimental identification of protein kinases' (PKs) substrates with their phosphorylation sites is time-consuming and often restricted by the availability of enzymatic reactions. Phosphorylation sites prediction with their specific kinase from machine learning approaches based on their primary sequences is favorably needed, for these methods can provide fast and automatic annotations, which can be used as guidelines for further experimental consideration. In this paper, we presented a modified k-Nearest Neighbor (k-NN) method measured by the Manhattan distance for phosphorylation site prediction. BLOSUM62-based similarity scores between two phosphorylation sites were adopted as the input vectors. Leave-one-out testing on two PK groups, PKA and CK2, shows that it outperforms two existing methods, Scansite and NetPhosK, which suggests that this method is another competitive computational approach in this branch of bioinformatics. PMID- 17281649 TI - Open source software infrastructure for computational biology and visualization. AB - The CMISS software package is used in many biological research areas for multiscale computational biology and visualization. Some major components of this suite have recently been released under an open source license, specifically modules for field storage, 3D graphics, mathematical field operators and image processing. Interfaces are being developed to facilitate integration with other applications and the Internet. PMID- 17281650 TI - Diagnosis of breast cancer using HPLC metabonomics fingerprints coupled with computational methods. AB - The present study was focused on developing a computational procedure for analysis of the HPLC metabonomics fingerprints of human urine to distinguish between patients with breast cancer from healthy people. The predictive rate of support vector machine (SVM) based diagnosis model is 100% for training set and 93.2% for test set, respectively. Current work might have important reference values to explore the methodology of metabonomics. PMID- 17281651 TI - Spatiotemporal neuronal signaling by nitric oxide: diffusion-reaction modeling and analysis. AB - Nitric oxide (NO) is a neurotransmitter strikingly different from others. It is able to diffuse isotropically regardless of intervening cellular or membrane structures; and it exhibits a surprisingly diverse range of biochemical activity. NO diffusion and reactions affect the nervous system significantly. At present there is no effective technique for detecting them in vivo in real time, whereas computational modeling and simulation helps us gain insight into them. Existing models and simulations for the purpose, however, are inadequate as only the diffusion or only the reactions have been considered. For a comprehensive study of the gaseous neurotransmitter NO, both the diffusion and biochemical reactions should be taken into consideration. This paper, where NO diffusion and reactions are considered as a whole system, presents a spatiotemporal analysis of NO diffusion-reaction, taking the case with brain hypoxia as an example. The analysis is illustrated with a diffusion-reaction model and graphic simulation, which particularly describe how the concentration of oxygen (O2) affects NO signaling in a neuron involved in brain hypoxia. PMID- 17281652 TI - Hidden Markov model analysis of motifs in interleukins and haematopoietic growth factor family. AB - Haematopoietic cytokines are important in the regulation of haematopoiesis and immune responses, and they can also influence lymphocyte development. Hundreds of members of several different cytokines families have been discovered by some different methods. But fast evolution rate and low similarity of cytokines prevent identifing novel members of a cytokine family completely with classical tools such as BLAST. Here hidden markov model algorithm is performed on Haematopoietic cytokines and inerleukin 10 (IL10) related family, and two motifs are discovered. Then, three famous protein sequence databases(SwissProt, IPI and Nr) were scanned using each motif respectively, which leaded to evaluate the relation between motif and every sequence of database including some unknown proteins or some ambiguous function proteins of known families. Furthermore, the biology features were compared to filter novel members of cytokines. As a result, four proteins are predicted to be the cytokine candidates. PMID- 17281653 TI - Assemble worldwide biologists in a network construct a web services based architecture for bioinformatics. AB - The Internet has already deflated our world of working and living into a very small scope, thus bringing out the concept of Earth Village, in which people could communicate and co-work though thousands' miles far away from each other. This paper describes a prototype, which is just like an Earth Lab for bioinformatics, based on Web services framework to build up a network architecture for bioinformatics research and for world wide biologists to easily implement enormous, complex processes, and effectively share and access computing resources and data, regardless of how heterogeneous the format of the data is and how decentralized and distributed these resources are around the world. A diminutive and simplified example scenario is given out to realize the prototype after that. PMID- 17281654 TI - Using CellML in computational models of multiscale physiology. AB - A computational modeling framework is presented which enables the integration of multiple physics and spatial scales in models of physiological systems. A novel aspect of the framework is the use of CellML to specify all model and simulation specific mathematical equations including cellular models and material constitutive relationships. Models of cardiac electromechanics at cellular, tissue, and organ spatial scales are used to illustrate the developed and implemented framework and other applications are discussed. PMID- 17281655 TI - Glioblastoma multiforme treated by the chemotherapeutic agent temozolomide in vivo: a 4D simulation model of the tumor response. AB - A novel four dimensional, patient specific simulation model of solid tumor response to chemotherapeutic treatment in vivo is presented. The special case of glioblastoma multiforme treated by temozolomide is addressed as a simulation paradigm. The model is based on the patient's imaging, histopathologic and genetic data. For a given drug administration schedule Iying within acceptable toxicity boundaries, the concentration of the prodrug and its metabolites within the tumor is calculated as a function of time based on the drug phramacokinetics. A discretization mesh is superimposed upon the anatomical region of interest and within each geometrical cell of the mesh the most prominent biological "laws" are applied. The biological cell fates are predicted based on the drug pharmacodynamics. The outcome of the simulation is a prediction of the spatiotemporal activity of the entire tumor and is virtual reality visualized. A good qualitative agreement of the model's predictions with clinical experience has strengthened the applicability of the approach. Long term clinical and quantitative adaptation and validation as well as modeling the normal tissue reactions are in progress. The proposed model primarily aims at providing a reliable platform for performing patient individualized in silico experiments as a means of chemotherapeutic treatment optimization. PMID- 17281656 TI - The development of a VR-based treatment planning system for oncology. AB - In this study, an oncology treatment planning system was developed by integrating the techniques of computer graphics, virtual reality (VR) and three dimensional (3D) image reconstruction. The virtual treatment room was constructed according to the real space, and the 3D data of patient's body was reconstructed from computer tomography (CT) slices in order to provide the 3D clinical information to compare with the therapy in real world. In addition, the virtual multi-leaf collimator (MLC) was constructed to simulate and visualize both the radiation and irradiation fields. All objects in the system had been scaled down according to the true size. The system can be expected to save the preparation time and can be used for teaching and training prior to a real therapy. PMID- 17281657 TI - N-phosphorylamino acids and penta-coordinate phosphorous compounds in the chemical process of life. AB - N-phosphorylamino acids can react to form esters, peptides, phosphoryl ester exchanged products and phosphoryl group migration products under mild conditions which are very important in researches on the origin of life. It has been proposed that the penta-coordinate phosphorous compounds might be the common intermediates of these reactions, which are the key factor to determine the activities. In this paper, the mechanisms of series reactions involving N phosphorylaminoacids and penta-coordinate phosphorous compounds are studied with computational chemistry methods. PMID- 17281658 TI - 2-D mathematical models of Tumor-induced angiogenesis. AB - Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is a process in which capillary sprouts are formed in response to externally supplied chemical stimuli. Tumor-induced angiogenesis plays a significant role in tumor's growth, metastasis, in which endothelia-cell is the most active member engaging in various stages, including the secretion and diffusion of various tumor-induced angiogenesis factors (TAF); the nascent endothelial cell migrates towards a particular direction and position under the interaction of a series of internal and external factors; eventually the new formed capillaries reach and penetrate the tumor. At present there is no technique of medical image to accurately investigate the micro-vessel net of tumor, it makes some hard in clinical treatment of tumor. In this paper we present a 2-D mathematical model, which takes into account essential endothelial cell-extra cellular matrix interactions, and the response to chemical stimuli (TAF) mentioned above, to describes the formation of the capillary sprout network in response to physiological conditions around tumor especially investigate the process inside tumor in terms of the complex features of tumor. This theoretical capillary networks generated by computer simulations provide a premise for the further research. PMID- 17281659 TI - Visual modeling and simulation of adaptive immune system. AB - A visual modeling approach and its computational technique were proposed to represent and simulate a kind of adaptive immune system. Because adaptive immune system is comprised of immune cells and immune molecules etc, the hierarchical model of the immune system is proposed, more faithful and suitable for visual simulation than traditional models. The hierarchical immune system mainly consists of inherent immune tier, adaptive immune tier and immune cell tier. The tri-tier model of the immune system is seamless and coherent with the architecture of the artificial immune system. At last, the visual result of the simulation shows that the visual modeling approach can provide an effective way of understanding the adaptive immune system. PMID- 17281660 TI - An ontology for protein data models. AB - Accelerating availability of protein sequences and structures has transformed both the theory and practice of computational biology. The current systems of nomenclature for proteins remain divergent even when the experts appreciate the underlying similarities. Interoperability of protein databases is limited to lack of progress in the way the biologists describe and conceptualize the shared biological elements in protein data. The goal of the proposed protein ontology is a step forward to address these concerns by is producing a structured vocabulary that can be applied to all proteins even as the knowledge of protein roles in the cells is still accumulating and changing. A Database of 10 Major Prion Proteins available in various Protein data sources, based on the vocabulary provided by Protein Ontology is made available. PMID- 17281661 TI - Sleep apnea detection using an adaptive fuzzy logic based screening system. AB - We report an adaptive diagnostic system for the classification of breathing events for the purpose of detecting sleep apnea syndromes. The system employs two classification engines used in series. The first engine is fuzzy logic-based and generates one of three outcomes for each breathing event: normal, abnormal, and not-sure. The second classification engine is based on a center of gravity engine which is trained using the normal and abnormal events, generated by the first engine, and is specifically designed for sorting out the not-sure events. The fuzzy logic engine can be tuned very conservatively to reduce or eliminate the chance of error at the first stage. Since the second engine is trained adaptively using normal and abnormal data of the same patient, its accuracy is generally better than relying on multi-patient training approaches. The two-step, adaptive nature of the system allows for high accuracy and lends itself well for practical implementation. PMID- 17281662 TI - Simulation of pulmonary pathophysiology during spontaneous breathing. AB - This paper presents a functional model of lung mechanics including a non-linear alveolar pressure volume curve and representation of the work of respiratory muscles during breathing. The model is used to simulate the response to forced inspiration and expiration, and these simulations compared to the standard results of lung function tests routinely performed in departments of lung medicine. The model can simulate the characteristics of inspiratory and expiratory flow profiles seen in normal subjects, and in patients with obstructive or restrictive diseases. PMID- 17281663 TI - Sleep apnea detection and classification using fuzzy logic: clinical evaluation. AB - We have previously reported a system suitable for detection and classification of sleep apnea syndromes. This paper reports the results of the clinical evaluation of the proposed system. In the current implementation, the system uses breathing signals: nasal flow, thorax movement, and abdomen movement. The detection part of the system uses only the nasal flow signal to detect apnea employing two engines used in series. It then feeds segments labeled as abnormal to the classification part of the system, which uses the center of gravity of each segment to determine the type of abnormality: obstructive, central or hypopnea. In comparison to other systems, this implementation can be shown to be simpler and more accurate. When the low implementation cost is taken into consideration, the proposed system has a substantial potential for being used as a screening device. PMID- 17281664 TI - Influences of hypoxia on auditory evoked potentials of conscious humans. AB - Early cortical auditory evoked potentials (AEP) from eleven volunteers undergoing an arterial oxygen desaturation procedure have been recorded and analysed. During the procedure the arterial oxygen saturation was decreased from 100% gradually down to 70%. Changes of the latency and amplitude of the AEP could be detected on the conscious subjects thus excluding any influences of anaesthesia. It was found that as oxygen desaturation went down the latency increased significantly and the amplitude also slightly increased but with no statistic significance. The latency parameters, especially Pb latency, are more sensitive to hypoxia than the amplitude parameters. The changes are similar to the effect of induction of anaesthesia. PMID- 17281665 TI - Evaluation of the effect of postural and gravitational variations on the distribution of pulmonary blood flow via an image-based computational model. AB - We have developed an image-based computational model of blood flow within the human pulmonary circulation in order to investigate the distribution of flow under various conditions of posture and gravity. Geometric models of the lobar surfaces and largest arterial and venous vessels were derived from multi-detector row X-ray computed tomography. The remaining blood vessels were generated using a volume-filling branching algorithm. Equations representing conservation of mass and momentum are solved within the vascular geometry to calculate pressure, radius, and velocity distributions. Flow solutions are obtained within the model in the upright, inverted, prone, and supine postures and in the upright posture with and without gravity. Additional equations representing large deformation mechanics are used to calculate the change in lung geometry and pressure distributions within the lung in the various postures - creating a coupled, co dependent model of mechanics and flow. The embedded vascular meshes deform in accordance with the lung geometry. Results illustrate a persistent flow gradient from the top to the bottom of the lung even in the absence of gravity and in all postures, indicating that vascular branching structure is largely responsible for the distribution of flow. PMID- 17281666 TI - Monitoring of wheeze duration during spontaneous respiration in asthmatic patients. AB - Respiratory sound analysis can offer important information related to pulmonary diseases. Wheezes have been reported as adventitious respiratory sounds in asthmatic or obstructive patients, during forced exhalation maneuvers. In this work, we propose a method for monitoring and analysis of respiratory sounds in frequency domain, during spontaneous ventilation. The database analyzed was acquired during spontaneous ventilation for 120 seconds (DBsv), of 26 asthmatics patients. Using an autoregressive model (AR, order 16), the Power Spectral Density (PSD) was calculated for every phase of expiration and inspiration and the maximum frequency (fp) was estimated. From this parameter we study the time duration of the wheezes. The effect of bronchodilator inhalation in asthmatic patients was studied analyzing the duration of the wheezes in the bandwidth 600 2000 Hz (HFband). The wheeze duration is evaluated as the number of consecutive segments, with fp is inside of HFband, (for 3 or more segments in a cycle). The difference of the wheeze duration inside the respiratory cycles (Dwheez), before and after bronchodilator inhalation (POST) was evaluated. It was found a good correlation between Dwheez and FEV 1% improvement (FEV 1%_imp), for FEV1%_imp greater than 8%, whereas values FEV1%_imp less than 8% did not show any change of Dwheez. This last result suggests no difference in the wheeze duration between the baseline and POST records. This method could predict the FEV1%_imp by means of estimation of Dwheez during spontaneous ventilation. PMID- 17281667 TI - Comparison of respiratory rate estimation based on tracheal sounds versus a capnograph. AB - The objective was to compare the accuracy of estimations of respiratory rate (RR), based on tracheal sounds, with simultaneous estimations from a capnograph, using as a common reference a pneumotachometer. Five subjects without pulmonary diseases were enrolled. Tracheal sounds were acquired using a contact piezoelectric sensor placed on the subject's throat and analyzed using a combined investigation of the sound envelope and frequency content. The capnograph and pneumotachometer were coupled to a face mask worn by the subjects. There was a strong linear correlation (r2= 0.98) between the acoustic method and the pneumotachometer and also between the capnograph and the pneumotachometer (r2 = 0.98). The SEE obtained by the acoustic method was 1.11 and the SEE obtained by the capnograph was 1.23. As a conclusion, the accuracy of the respiratory rate estimated from tracheal sounds on adult subjects was comparable to the accuracy of a commercial capnograph, using as a common reference a pneumotachometer. PMID- 17281668 TI - Acoustic feedback system with digital signal processor to alert the subject and quantitative visualization of arousal reaction induced by the sound using dynamic characteristics of saccadic eye movement: a preliminary study. AB - A new system has been developed to assess human alertness and to alert the subject with acoustic stimulation in accordance with the assessed level of alertness. Dynamic characteristics of saccadic eye movement (saccade: SC) were used to calculate an alertness index. Digital signal processor was adopted for the calculation. The system was tested through eye tracking tasks. The results indicated that the developed system could awaken the subject by feeding sound back to the subject. Also, arousal reaction induced by the sound was visualized quantitatively by analyzing values of the alertness index after the stimulation. These results indicate applicability of the system not only to awakening device for accident prevention, but also to a tool for investigating effects of the stimulation. PMID- 17281669 TI - Pulse transit time-derived respiratory parameters and their variability across sleep stages. AB - We considered the capability of pulse transit time (PTT) to provide respiratory information in obstructive sleep apnea (OSA) patients. PTT-derived respiratory frequency was quite well correlated with that derived from inductance plethysmography, with amplitude slightly less so. The PTT-derived respiratory estimates were also used to distinguish sleep stage. In some subjects, statistically significant differences in respiratory parameters were observed between Wake, REM, and Stage 2 sleep, but this effect was highly subject dependent. PMID- 17281670 TI - Approximate entropy from overnight pulse oximetry for the obstructive sleep apnea syndrome. AB - The aim of this preliminary study was to asses whether a time series analysis from overnight pulse oximetry by means of Approximate Entropy (ApEn) could yield essential information on the diagnosis of obstructive sleep apnea (OSA) syndrome. We analyzed the oxygen saturation (SaO2) signals of 74 patients (44 with a positive diagnosis of OSA and 30 with a negative diagnosis of OSA) by means of ApEn, which quantified the regularity (or complexity) of time series. Results showed that recurrence of apnea events in patients with OSA determined a significant increase in ApEn values with a mean .. standard deviation (SD) of 1.07 +/- 0.30. A mean +/-SD ApEn value of 0.47 +/- 0.25 was estimated in patients without OSA. We obtained an area under the ROC curve of 0.94. The optimum threshold was selected at 0.81, where we achieved a 79,5% sensitivity and 90% specificity. Further analyses are necessary with new and larger data set to test the potential value of our methodology prospectively. PMID- 17281671 TI - Determination of pulmonary gases (O2 & CO2) metabolic-rates and lung diffusion coefficients based on the inspired and expired air compositions and venous blood and gas concentration. AB - The primary function of the lung is to (i) oxygenate the blood and thereby provide oxygen to the cells for metabolization purposes, and (ii) to remove the CO2 produced by the tissues from the pulmonary blood. Herein, we provide a noninvasive methodology to asses the capacity of the lung to oxygenate the pulmonary capillary blood and to reduce its CO2 concentration. For this purpose, we analyze the compositions of the inspired and expired air per breath, and therefrom compute the metabolic O2 consumption rate (VO2) and CO2 production rate (V CO2). Next we compute the cardiac out (CO) as CO = V O2(CAB O2 - CVB O2). We have derived the expressions for diffusion coefficients (i) DO2 in terms of VO2 and the alveolar and venous partial pressures, Pal O2 and PVB O2 and (ii) DCO2 in terms of VCO2, Pal CO2 and PVB CO2. The coefficients DO2 and DCO2 represent the gas transfer capacity of the lung. The paper provides a case study for the determination of Q, DO2 and DCO2. The derived information of DO2 and DCO2 as well as of O2 and CO2 metabolic rates can be of considerable clinical use including for SARS assessment. PMID- 17281672 TI - Nonlinear finite element analysis of C0-C1-C2 complex under physiologic loads. AB - The aim of the present study is to develop a comprehensive, geometric, nonlinear finite element model of the occipito-atlanto-axial (C0-C1-C2) complex. More accurate geometric and material properties profited from Visible Human Male dataset which was introduced for the first time in the finite element research of the cervical spine. The biomechanical response of the model was validated and corresponded closely with the published experimental data under the four physiologic loading modes. The study shows that, in the physiologic range of motion of the neck, the ligaments are the overriding roles on the kinematics of the human upper cervical spine. PMID- 17281673 TI - Identification of spinal deformity classification with total curvature analysis and artificial neural network. AB - In this study, a multilayer feedforward, back-propagation Artificial Neural Network is implemented to identify the classification patterns of the scoliotic spinal deformity. At first step the simplified three-dimensional spine model is constructed from coronal and sagittal x-ray images. The features of the central axis curve of the spinal deformity patterns in 3D space are extracted by the Total Curvature analysis. The discrete form of the Total Curvature, including the curvature and the torsion of the central axis of the simplified 3D spine model is derived from the Difference Quotients. The values of Total Curvature of 17 vertebrae from first thoracic to the fifth lumbar spine formed a Euclidean space of 17 dimensions. Either the curvature or the torsion of the three-dimensional curve of the central axis of the spine model could provide the input of the artificial neural network. The King Classification model is tested on the neural network. Five sets of King spinal deformity patterns are randomly selected by the definition of King classification. The output layer of the artificial neural network has five neurons representing the five King classification types. The network validation was conducted by the Hold-Out method, one of Cross-Validation variant. The performance of the neural network is compared between two network topologies, one with one hidden layer and another with two hidden layers. The results are shown in a table with each of five datasets leave-out and all five datasets participating the training, with either one hidden layer or two hidden layer network. PMID- 17281674 TI - The multi-level angular deformity determination in 3D space with total curvature analysis for long bones. AB - Determination of angular deformity apex and plane for long bone is one of the tasks in our preoperative surgery planning system. Long bone angular deformity of the upper and lower extremities, in general, is three-dimensional. In our computerized planning system, the simplified long bone is represented by two components. One is the three-dimensional curve of its central axis, which as indicated in our previous study, is obtained from both frontal and lateral x-ray image outlines. Another component is represented by a series of ellipses in the horizontal planes centralized with this central axis. The central axis can be described by Total Curvature, which contains both the curvature and the torsion of this 3D curve of the central axis. The curvature measures how sharply a curve is turning and the torsion measures its twist in 3D space. In our previous study, the assumption was made that the angular deformity planes determined by the central axis always bisected the coronal and sagittal plane, i.e. these planes are perpendicular to the horizontal plane. However, this is not true for multi level angular deformity and the deformity planes should be arbitrary in 3D space. The improved method we are using is to apply the Total Curvature to the central axis of the long bone. The curvature and torsion could completely define the shape of this 3D curve of central axis. By analyzing the central axis of the long bone with the Total Curvature, the severity and the level as well as the plane of the deformity of the long bone in 3D can be determined automatically. PMID- 17281675 TI - A microcontroller-based implantable nerve stimulator used for rats. AB - A microcontroller-based stimulator that can be flexible programmed after it has been implanted into a rat was studied. Programmability enables implanted stimulators to generate customized, complex protocols for experiments. After implantation, a coded light pulse train that contains information of specific identification will unlock a certain stimulator. If a command that changing the parameters is received, the microcontroller will update its flash memory after it affirms the commands. The whole size of it is only 1.6 cubic centimeters, and it can work for a month. The devices have been successfully used in animal behavior experiments, especially on rats. PMID- 17281676 TI - The influence of changes in patellar and femoral prosthesis on knee extensor mechanism after TKA. AB - In order to study the influence of some position changes of prosthesis in patello femoral joint on knee mechanism after total knee arthroplasty, a three dimensional model of knee joint including patello-femoral joint has been developed. Changes in position parameters of patellar or femoral prosthesis were simulated. Patellar lateral transition, ratio of patellar tendon force to quadriceps force, and ratio of patello-femoral compressive force to quadriceps force are choosing to response performances of knee extensor mechanics. Results show that patellar thickening, patellar medial rotation, lateral rotation and forward rotation of femoral prosthesis will all increase the patello-femoral compressive force. And patellar thickening, patellar medial rotation, medial rotation and forward rotation of femoral prosthesis will also result in increase of ratio of patellar tendon force to quadriceps. And patellar medial rotation, medial rotation and forward rotation of femoral prosthesis will result in increase of patellar lateral translation. PMID- 17281677 TI - Biomechanical evaluation of unilateral maxillary defect restoration based on modularized finite element model of normal human skull. AB - A standardized and modularized finite element model of a normal human skull is established to simulate the unilateral defective pattern of the maxillary and the stress distribution of craniofacial skeleton with repair subject to the bite force. Based on the model, the stress evaluation of autologous bone grafted and zygomatic implant is to optimize the repairing method, and to rebuild the occlusal function. PMID- 17281678 TI - Design and biomechanical evaluation of a custom lateral mandible titanium prosthesis. AB - A large mandibular discontinuity defect is most often due to severe trauma, infection or resection for neoplasm. Reconstruction plates have been popularly applied to bridge mandibular defects without bone grafting. The esthetics and continuity of the mandible with segmental defects could be rehabilitated successfully. However, the function is difficult to reconstructed using this type of plate. Furthermore, skin or mucosa perforation, plate fracture and loss of screw retention were the serious complications resulting in reconstruction failure. In this paper, a lateral biomechanical titanium mandibular prosthesis (BMMP) with new retention structure has been design. Problems of masticatory muscle attachment and other soft tissue overlay on the prosthesis have been considered. The biomechanical effect of the BMMP has been analysed by the three dimensional finite element method (FEM). And the analysis of biomechanical effects of the retention on the BMMP was performed comparing with that of traditional reconstruction plate. Analysis results have shown that the BMMP was of better load conductibility and reliable retention. The function, continuity and esthetics of the mandible bone with a lateral defect were reconstructed successfully using the BMMP. PMID- 17281679 TI - Biomechanics of lumbar vertebrae as a functionally optimal structure. AB - In this paper, we demonstrate that the spinal vertebral body (VB) remodels (as per Wolf's law) such that its shape and dimensions enable it to be a light-weight high-strength structure. The VB is modeled as a hyperboloid shell, whose generators are shown to sustain (and transmit) all the loadings on the VB as axial forces. Upon minimizing the sum of the forces in the hyperboloid VB generators with respect to its shape parameters theta (the angle between pairs of generators), we obtain the optimal shape-dimensions of the VB which corresponds to its measured shape-dimensions. This parameter theta is deemed to be the prime shape parameter of the hyperboloid VB. PMID- 17281680 TI - Experimental research on the biomechanical properties of the rabbit iris. AB - OBJECTIVE: To qualify the mechanical properties of the iris during its passive deformation under the condition of glaucoma. MATERIAL AND METHODS: Experiments simulating the total pupillary block was performed on isolated rabbit irises to determine the passive mechanical behavior of the intact iris. RESULTS: The relationship between the area strain(delta) and the pressure of posterior chamber relative to the anterior chamber(P') was obtained: (P1) was obtained P'+b eb1 delta. PMID- 17281681 TI - Measurement of elastic properties of blood vessels. AB - This paper is related to the measurements of the modulus of elasticity of an artery by studying the deformations due to the inflation of an angioplasty balloon catheter used for Interventional Radiology (IR) procedures. Various types of balloons are studied in order to characterize and compare their behaviors at the time of inflation. A test bench, consisting of an angioplasty balloon, a Polyvinyl alcohol model and an actuator used to inflate a balloon, is developed for the realization of the experiments. The pressure-volume curve during the inflation of a balloon is observed. Elasticity modulus are derived with an analytical model of the measurement system. The results are then analyzed and compared to existing data from literature. PMID- 17281683 TI - The implementation of a multi-channel interferential current electrical stimulation system. AB - In this paper, we developed a signal generation method which can be used in the interferential current electrical stimulating device. A low-cost, 8-bit microcontroller and a very compact algorithm were adopted here to generate the sine wave. Using the method, we can easily modify the frequency and phase difference between two channels with high resolution. The preliminary experiment shows that this method can reduce the circuit complexity and improve the signal stability. PMID- 17281682 TI - Effects of functional electrical stimulation relating to leg movement. AB - Functional electrical stimulation (FES) has grown to be an effective and important element in the biomedical industry over the years. Due to this fact, it has become the basis of many researches. However, much work is focused on the theory and control technique with very few relating experiments. In this work, some key experiments were performed on the leg muscles during the leg movement. Some useful results were obtained with regards to muscle reaction, in terms EMG readings. The stimulus of the FES system was also applied to the muscles during the leg movement. The readings of experiments reveal some important muscle properties which are verified accordingly. PMID- 17281684 TI - Application of nonlinear model predictive controller for fes-assisted standing up in paraplegia. AB - Functional electrical stimulation (FES) is a method of restoring functional movements in patients of spinal cord injury that electrically induces muscle contractions. Nonlinear dynamics of paraplegics during standing up and limits of the physiological actuators suggest "Nonlinear Model Predictive Control" as a good candidate to follow desired trajectory and maintaining standing no need to learning or tuning many parameters such as many nonlinear controllers that had been used previously. In this work, the theoretical possibility of FES assisted standing up in paraplegic patient is studied using Nonlinear Model Predictive Control approach by computer simulation. The proposed controller shows good tracking behavior for ankle, knee and hip joint angles in simulated paraplegic standing up and improves patient safety because of considering constraints in control. PMID- 17281685 TI - Influence of time-varying magnetic field on the release of neurotransmitters in raphe nuclei of rats. AB - A specially-designed time-varying magnetic field was developed to treat insomnia. Clinical results showed that this method could shorten the time to go to sleep and prolong the sleep duration. However, the mechanism of this method is still not well understood. In this study, the effect of magnetic stimulation on the release of serotonin (5-HT), noradrenaline (NE), dopamine (DA) in raphe nuclei of rats, which are known to play an important role in the sleep-wake regulation, was investigated. It was shown that there was a significant difference in the release of serotonin between control group and experimental group (p<0.01). The release of serotonin of the experimental group increased significantly. No obvious release changes of NE and DA are found (p>0.05). The results indicates that one possible mechanism of inducing sleep using specially designed magnetic field is to change the release of sleep-related neurotransmitters. PMID- 17281686 TI - Excitation properties of peripheral nerves stimulated by an induced transverse electric field during magnetic stimulation. AB - Interest in magnetic stimulation (MS) of peripheral nerves has grown rapidly, but difficulties in determining excitation sites and computing the stimulation efficiency have prevented magnetic stimulation from becoming a routing clinical tool. The classical cable function has demonstrated that the activating function of nerves is the first spatial derivative of the electric field component parallel to the nerves. Therefore, excellent analyses have been presented in the literatures which predict the excitation properties, for peripheral nerves stimulated by the induced electric field component parallel to the nerves during MS. There is not, however, an adequate analysis for nerves excitation which considers the induced field component perpendicular to the fibers. Based on the improved cable function, which introduces a transverse field component, we have analyzed the excitation sites and the stimulation efficiencies during MS using round coils and 8-shaped coils, respectively. That is helpful to the further development of the functional magnetic nerve stimulation technique and to the clinical application of MS. PMID- 17281687 TI - The optimal design of magnetic coil in transcranial magnetic stimulation. AB - Transcranial magnetic stimulation (TMS) is a new tool for the study of the human brain and for neurological therapeutics. Magnetic coil design is very important in the TMS technique. Precise spatial localization of stimulation sites is the key of efficient functional magnetic stimulations. This paper develops circular coils, figure-of-8 coils and coil array elements in order to realize a transcranial magnetic stimulator, and analyses the coil properties. The results show that different coils have different focus. PMID- 17281688 TI - A method for identification of electrically stimulated muscle. AB - We present a model structure and a method for identifying the dynamics of electrically stimulated muscle. The model structure is sufficiently rich to describe a wide set of muscle behavior. It consists of (i) an input static nonlinearity representing the muscle's recruitment properties, (ii) a linear dynamical system representing the contraction dynamics, (iii) an output static nonlinearity representing generalized force- length and force-velocity relationships, and (iv) prefilters for the mechanical input that capture impedance and history dependence properties of the muscle. It is assumed that each of the subsystems is linearly parameterized. We present parameter estimation methods, and verify via simulation successful convergence of the estimates to their true values with small variances. PMID- 17281689 TI - Therapeutic protein production in vivo after electroporation-assisted intramuscular gene delivery. AB - Gene delivery to skeletal muscles assisted by electroporation(EP) is a promising strategy for in vivo production of the therapeutic proteins. But the commonly used procedure required the application of electric pulses with voltages at above 200V/cm and durations at least 40ms, which would result in several damages in the muscle and limited surviving cells expressing transgene. We reported here an optimization study of the various electric pulse parameters to reduce toxicity while maintain transgene expression. In addition, we also found that the secreted transgene product level detected in serum samples may not correlate with the total gene expression level in muscles. Based on our data, we'd propose some less damaging electroporation parameters that may be useful for intramuscular gene delivery and therapeutic protein production. PMID- 17281690 TI - Preliminary assessment of remote photoelectric excitation of an actuator for a hearing implant. AB - Sound modulated infrared (IR) light, as an alternative signal (and energy) transmission method, was evaluated for remote powering of a hearing implant via an implanted photodiode receiver. One human cadaveric temporal bone was used to test this concept by locating an IR source (LED) in the ear canal 4 mm away from the eardrum and a photodiode in the middle ear cavity. The photodiode output was directly used to drive a piezo-ceramic disc actuator which was located externally for facilitating the test. The displacement frequency response of the actuator was measured by a laser vibrometer. It was found that, at a LED current of 8.6 mA, the actuator displacement was about 22.4 nm, equivalent to a stapes displacement from about 91 dB sound-pressure-level (SPL) stimulation at the eardrum. The IR light transmittance through the eardrum (compared to through an air path) was about 67%. The LED optical power was 0.77 mW (its maximal irradiance was about 3.95 mW/cm2) which is a safe to the human body. Current consumption can be reduced by a factor of 3-5 by using a more efficient LED and photodiode. PMID- 17281691 TI - Wireless real-time head movement system using a personal digital assistant (PDA) for control of a power wheelchair. AB - Loss of mobility can occur for a variety of reasons, such as spinal cord injury or motor neurone disease. The onset of these conditions often brings with it an associated loss of personal independence, which is primarily due to the fact that the sufferer is no longer able to control their mobility. This project aims to address this problem through the creation of a head movement based wheelchair control system. Using a personal digital assistant (PDA) artificial intelligence techniques on an embedded LINUX operating system, a wireless head movement wheelchair control system has been designed and implemented. This system provides relief for sufferers of conditions which inhibit mobility through a method of wheelchair control which offers enhanced ease of use, attractiveness and independence. PMID- 17281692 TI - Elastic path controller for assistive devices. AB - Robotic assistive devices that constrain motion along pre-defined paths are useful in reducing maneuvering efforts by human. This paper introduces an Elastic Path Controller (EPC) that adds "elasticity" to the path following and enables dynamic modification of the paths. This permits the users to compensate for changes in the environment such as introduction of new obstacles or for errors in position sensing. The experiments performed on a Scooter cobot show that users can learn to use this novel tool to modify and design guiding paths in a relatively simple way. The operators use the EPC by pushing/pulling against the guided paths to produce the desired deformations. Then, by just dropping the forces and trusting the path controller, they will be brought back to the guided paths. PMID- 17281693 TI - Measurement and analysis of reflex Responses to perturbation during walking towards the realization of artificial reflex. AB - Reflex responses play an important role in gravity resistance, balance maintenance and the reaction to perturbation during human walking and standing upright. In this study, aiming at the realization of artificial reflex for paralyzed people, whose reflexive system was also impaired to a certain degree because of the weakened afferent neural pathway, the reflex responses of normal subjects were measured and analyzed. Not only the sensors for measuring muscle activation, but also the sensors for measuring body motion were employed. The spatiotemporal relation between muscle activity and body motion was qualitatively analyzed. Moreover, the candidates for artificial reflex triggering signal were identified for further investigation. PMID- 17281694 TI - Nodule detection in 3D chest CT images using 2nd order autocorrelation features. AB - We have developed a new recognition approach using 2nd order autocorrelation and multi-regression analysis to detect a small (<7mm in diameter) lung nodules in chest 3D CT images. By combining our previous detection method of the template matching based on genetic algorithm, the detection performance was 94% true positive rate at 2.05 false-positive marks per case using leave-one- out study. PMID- 17281695 TI - An improved correction method for reducing off-focal artifacts in CT imaging. AB - This paper presents a new method to reduce halo artifacts in Computed Tomography (CT) images, which blur the image edges and descend the image quality. Off-focal radiation is main ill factor leading to these halo artifacts. To reduce the off focal effects, we adopt a pre-processing method to filter the sampling data directly before reconstruction, instead of post-processing method such as edge enhancing on the reconstructed images. Different from the prior pre-processing method, we also present a new and more practical method to obtain convolution kernel and a simpler formula in this paper. Results show that after calibration by the new practical method, the off-focal radiation effects were reduced efficiently, the edges were enhanced and the image quality was improved without increasing noise. PMID- 17281696 TI - Ultrasonic renal-stone detection and identification for extracorporeal lithotripsy. AB - The efficacy of extracorporeal shock wave lithotripsy (ESWL) depends greatly on the capability to focus shock waves on renal stone in real time. To achieve automatic focusing on moving targets, target detection, identification and tracking are required functions. An algorithm for renal stone detection and identification based on ultrasound images is proposed. Two types of image features (contrast and target shape) are selected for stone detection and identification. A feature extraction algorithm is proposed and tested. Statistical characteristics of these features are studied based on the images of kidney recorded during ESWL treatment. The results demonstrate the feasibility of automatic detection and identification of renal stone based on ultrasound images. PMID- 17281697 TI - A noval fragile watermarking method for medical images using quadtree structure. AB - This paper presents a new fragile watermarking scheme based on integral wavelet transform. The proposed method uses the quadtrees structures received by the wavelet decomposition, statistical information on the nodes and secret key to choose the locations where to embed the watermark. Only one bit watermark information will be hidden in the found position. Any changes on the fragile watermarked image will break the way to find out the correct position where the watermark is embedded. The preliminary experimental results indicate that the proposed method conforms to the human perception characteristics and provides a perceptually invisible fragile watermark with fewer image data modified, compared with some other conventional fragile watermarking methods. PMID- 17281698 TI - Interactive exhibition of human meridian based on Cult3D. AB - Acupuncture is the kernel of traditional Chinese medicine and is nowadays being accepted by the whole world. The precise orientation of the points and meridian is important in acupuncture while it is difficult to be done via the 2-dimension pictures. So the 3D interactive exhibition is undoubtedly superior to the traditional 2D way. A Web3D technology Cult3D and its advantages in contrast to VRML are presented. The implementation process of interactive human point exhibition by using Cult3D is discussed in detail. A primary attempt of expressing the knowledge system of meridian more intuitionisticly is made. PMID- 17281699 TI - Optimization based fingerprint direction field estimation. AB - Fingerprint direction field estimation is a key step among most of fingerprint enhancement systems, and so far, in most of systems it heavily relies on local ridge gradient information. However, this method is sensitive to noises and often results in poor estimation in regions where there are too much noises. In this paper, we introduce an effective algorithm to estimate the fingerprint direction field accurately. By using the global ridge characters, the fingerprint direction field is optimized from squared gradients. Experimental results indicate that our algorithm can improve the accuracy of the ridge direction estimation and reduce the influence of noises effectively. PMID- 17281700 TI - A segmentation scheme based on rayleigh distribution model for extracting glottal waveform from high-speed laryngeal images. AB - In this paper, a segmentation scheme that combines thresholding, morphological operation and region growing is proposed for tracing the vocal fold opening region from the high-speed laryngeal image sequences. Specifically, the proposed scheme contains three steps: 1), histogram based global thresholding; 2), morphological operation on the segmented binary output from step 1; 3), region growing process to refine the segmentation. The glottal area waveform, which is the glottis area as a function of time, is obtained on a frame by frame basis from the segmented region of the vocal fold opening, or glottis. Representative clinical image recordings from subjects with normal and pathological voices are processed to validate our approach. PMID- 17281702 TI - Analysis of the correlation between the facial temperature and the stenosis of carotid arteries. AB - Death caused by stroke above the age of 60 years placed second in the world, and is the fifth leading cause in people aged 15 to 59 years old. Several methods for early detection of stroke are magnetic resonance angiography, and carotid duplex, both diagnoses are cost and time consuming. This research is aimed to provide a noninvasive, cost effective, and rapid technique for diagnosing carotid artery stenosis by using thermography. In this study, 64 images from 32 people were used to analysis the correlation between the temperature of the face and the stenosis of carotid arteries by automatically selecting and calculating the mean and standard deviation of the facial temperature. We find that external carotid artery affects the facial temperature significantly. PMID- 17281701 TI - Automatic detection of region of interest based on object tracking in neurosurgical video. AB - Automatic detection of region of interest (ROIs) in a complex image or video, such as an angiogram or endoscopic neurosurgery video, is a critical task in many medical image and video processing applications. In this paper, we present a new method that addresses several challenges in automatic detection of ROI of neurosurgical video for ROI coding which is used for neurophysiological intraoperative monitoring (IOM) system. This method is based on an object tracking technique with multivariate density estimation theory, combined with the shape information of the object. By defining the ROIs for neurosurgical video, this method produces a smooth and convex emphasis region within which surgical procedures are performed. A large bandwidth budget is assigned within the ROI to archive high-fidelity Internet transmission. Outside the ROI, a small bandwidth budget is allocated to efficiently utilize the bandwidth resource. We believe this method also can be used to image-guiduance surgery (IGS) systems to track the positions of surgical instruments in the physical space occupied by the patient after some improvement. PMID- 17281703 TI - The identification and clustering analysis of auditory neurons for salicylated induced rat model. AB - Salicylate-induced rat model is one of the animal models for tinnitus study. In this study, a radial basis function neural network for automatic identification is firstly developed due to its features of easy training and learning. From the experimental results, the recognition rate is demonstrated to be as high as 98%. Not only the recognition rate is improved, but also it is very objective in analysis. Secondly, a support vector clustering is applied to neurons distribution analysis. Based on the clustering analysis, it is found that the cluster number and distribution area for the Salicylated-induced fos-labeled neurons are very different from those of controlled group. PMID- 17281705 TI - Segmentation of neuronal-cell images from stained fields and monomodal histograms. AB - Information from images taken of cells being grown in culture with oxidative agents allows life science researchers to compare changes in neurons from the Zellweger mice to those from normal mice. Image segmentation is the major and first step for the study of these different types of processes in cells. In this paper we develop an innovative strategy for the segmentation of neuronal-cell images which are subjected to stains and whose histograms are monomodal. Such nontrival images make it a challenging task for many existing image segmentation methods. We show that the proposed method is an effective and simple procedure for the subsequent quantitative analysis of neuronal images. PMID- 17281704 TI - 3D semi-automatic segmentation of the cochlea and inner ear. AB - Though interactive direct volume rendering produces meaningful images with high quality, it cannot display separate inner ear labyrinth or cochlea only by adjusting imaging parameters to suppress the surrounding structures. Novel semi automatic segmentation methods were presented to extract the cochlea and inner ear from spiral CT images. The cochlea was separated from the medical image volume by applying the 3D narrow band level set segmentation algorithm with user interaction introduced to locate the initial contour and adjust the parameters. The inner ear was extracted with a similar semi-automatic segmentation method: manual segmentation was first applied to remove several closely interconnected regions in boundary by viewing image volume slice by slice, then the 3D narrow band level set segmentation algorithm was used to complete fine segmentation on image volume. Generating 3D models of cochlea and inner ear structures with such methods not only takes advantage of the combination of 2D images with 3D volume but also saves much time of post-processing. The segmented results were rendered with the Marching Cubes surface rendering method. The correlation of the point on the resultant surface to the three orthogonal sections that intersect at that point on the surface was built to evaluate the segmented object and display the spatial relations of the anatomical structures. The performance of the presented semi-automatic segmentation methods is tested using spiral CT images of the temporal bone. PMID- 17281706 TI - Multi-modality medical image registration using support vector machines. AB - The registration of multi-modality medical images is an important tool in surgical application. We presented a method of computing different modality medical images registration of the same patient. It incorporates prior joint intensity distribution between the two imaging modalities based on registered training images. The prior joint intensity distribution is modeled by support vector machine. Results aligning CT/MR and Pet/MR scans demonstrate that it can attain sub-voxel registration accuracy. Furthermore, it is a fast registration method because support vector machine solution is sparse. PMID- 17281707 TI - Microcalcification detection in 3-d breast ultrasound. AB - The appearance of cluster of microcalcifications in mammography or sonography is an important indicator for malignancy. Microcalcifications are calcium deposits, which can be identified as tiny areas that are slightly brighter than surrounding tissue. Detection of mammographic microcalcification has been proposed in many studies. Since a microcalcification cluster is a three-dimensional (3-D) entity, its projection onto a two-dimensional (2-D) image results in a loss of spatial information and may also cause superimposition of individual calcifications within the cluster. This paper aims to use the 3-D ultrasound to determine microcalcifications. In each slice, the proposed method adopts the top-hat filter to find bright spots, and employs four 2-D criteria to select the spots as candidate microcalcifications. Finally, spots appearing in sequent slices at the same position are considered as a microcalcification. We suggest using a computer automatically to detect the microcalcification being feasible and microcalcifications being a very important criterion of malignancy on future developing the computer-aided diagnosis for ultrasound. In the future, this technique can be adopted in a computer-aided diagnosis system combined with other diagnosis features for improving the diagnosis performance. PMID- 17281708 TI - An adaptive markov model-based method to cluster validation in image segmentation. AB - The number of class should be detected as part of the parameter estimation procedure prior to image segmentation for segmentation algorithms. It is very important in theory and application for estimating the class number correctly. In this paper, an adaptive total energy criterion (ATEC) to cluster validation is proposed based on the Markov random field (MRF) in the image segmentation. The criterion is composed of two parts: one part is inner-energy, which describes the difference of data in the same class; another is inter-class energy, which describes the edge information. The correct class number can be obtained by minimizing the ATEC. The parameters are estimated by expectation maximum (EM) algorithm and maximum psedu-likelihood (MPL) algorithm. The complex computation is optimized by the mixture of simulated algorithm (SA) and iterated conditional mode (ICM). The experiments show that the class number can be automatically detected by adjusting the hyper-parameter in MRF. As a by-product, the segmentation can be obtained by the maximum a posteriori (MAP). PMID- 17281709 TI - Reagent-free automatic cell viability determination using neural networks based machine vision and dark-field microscopy in Saccharomyces cerevisiae. AB - Fermentation industries require in-situ real-time monitoring of cell viability during fermentation processes. For this purpose, reagent-free approaches are desired because they can be used for in situ analysis and reduce the system's complexity. We have developed an automatic way of determining cell viability via analysis of time-lapse image sequences taken by dark field microscopy without the aid of any additional reagents. The image processing is based on neural networks based machine vision, involving Principal Component Analysis (PCA) to investigate the dynamic information of intracellular movements. In consequence, the essential features as the vital sign of the target cells are discovered. Viability predictions using the Support Vector Machine (SVM) classifier have been done successfully on the datasets with different qualities. Accuracy up to above 90% has been obtained on the basis of image enhancement. Robustness of the system is proved by the results of the tests. The model organism we have used is Saccharomyces cerevisiae, however, this technique can promisingly be applied for the identification of cell viability of other organisms as well. PMID- 17281710 TI - 3D registration of ultrasound images based on morphology skeleton. AB - In order to eliminate displacement and elastic deformation between images of adjacent frames in course of 3D ultrasonic image reconstruction, elastic registration based on morphology skeleton was adopt in this paper. Feature points of connected skeleton are extracted automatically by accounting topical curvature extreme points several times. Initial registration is processed according to barycenter of skeleton. Whereafter, elastic registration based on radial basis function are processed according to feature points of skeleton. Result of example demonstrate that according to traditional rigid registration, elastic registration based on skeleton feature retain natural difference in shape for organ's different part, and eliminate slight elastic deformation between frames caused by image obtained process simultaneously. This algorithm has a high practical value for image registration in course of 3D ultrasound image reconstruction. PMID- 17281711 TI - Automated quantification of lymph node size and number in surgical specimens of stage II colorectal cancer. AB - An automated image analysis method for quantification of the size and number of lymph nodes in surgical specimens of stage II colorectal cancer is presented. The quantification is made using routine histopathologic sections of lymph nodes that have been dissected by pathologists from resection specimens. The hematoxylin and eosin stained sections on slides are imaged with a standard image scanner. Each obtained image can contain multiple slides. The first task is to detect the slides. Then, the lymph nodes are detected and their size is assessed using K means clustering and morphological image processing. The results are found to correlate well with results that have been obtained manually. The method has proven useful for predicting survival in stage II colorectal cancer. PMID- 17281712 TI - Liver fibrosis identification based on ultrasound images. AB - Diagnostic ultrasound is one of useful and noninvasive tools for clinical medicine. However, due to its qualitative, subjective and experience-based nature, ultrasound images can be influenced by image conditions such as scanning frequency and machine settings. In this paper, a novel method is proposed to extract the liver features using the joint features of fractal dimension and the entropies of texture edge co-occurrence matrix based on ultrasound images, which is not sensitive to changes in emission frequency and gain. Then, Fisher linear classifier and Support Vector Machine are employed to test on a group of 99 liver fibrosis images from 18 patients, as well as other 273 healthy liver images from 18 specimens. PMID- 17281713 TI - Proposal for Conceptual designing of An Innovative C-arm Calibration Target. AB - In the existing fluoroscopic-image-based orthopedic surgical navigation system, C arm calibration target has several shortcomings. In order to overcome these shortcomings, an innovative conceptual design for calibration target is proposed. If the redesigned calibration target can be materialized and substituted for the existing one, and relevant software can be adapted accordingly, performance of surgical navigation system is hopefully to be promoted, and development-running cost be decreased. PMID- 17281714 TI - Symbolic shape descriptors for classifying craniosynostosis deformations from skull imaging. AB - Craniosynostosis is a serious condition of childhood, caused by the early fusion of the sutures of the skull. The resulting abnormal skull development can lead to severe deformities, increased intra-cranial pressure, as well as vision, hearing and breathing problems. In this work we develop a novel approach to accurately classify deformations caused by metopic and isolated sagittal synostosis. Our method combines a novel set of symbolic shape descriptors and off-the-shelf classification tools to model morphological variations that characterize the synostotic skull. We demonstrate the efficacy of our methodology in a series of large-scale classification experiments that contrast the performance of our proposed symbolic descriptors to those of traditional numeric descriptors, such as clinical severity indices, Fourier-based descriptors and cranial image quantifications. PMID- 17281715 TI - Research on registration of human eye tissue images and its application. AB - Some methods for registration of human eyes tissue images were described in this paper. Firstly, the algorithm of moment and principal axes was used to register the image sequence of eye's tissue slices in the rough. Then, a modified segmentation-counting registration algorithm was proposed to register the image sequence more accurately, which is not only as precision as maximization of mutual information registration algorithm but also more effectively than it. It was proved by experimentation that this algorithm can 10 times quicken the speed of the maximization of mutual information registration algorithm. Some kinds of optimization algorithms, such as Powell, Brent, Gloden Section and the Second degree interpolation algorithms, had been applied to the registration of the image sequence. The results of the experimentations showed that the registration speed can be accelerated more than 300 times faster with these algorithms. PMID- 17281716 TI - Medical image description in content-based image retrieval. AB - Medical image description is an important problem in content-based medical image retrieval. Hierarchical medical image semantic features description model is proposed according to the main sources to get semantic features currently. Based on it, medical image description model combining low-level features and semantic features is proposed. Experimental results show that additional text taking as part of semantic features improves the image retrieval precision and recall. PMID- 17281717 TI - Novel method for correction of x-ray fluoroscopic image. AB - X-ray fluoroscopic images have been widely used in orthopedic surgery. Unfortunately, the inherent distortion deteriorates the quality of fluoroscopic image. To avoid the discontinuities of local correction techniques and achieve good accuracy in present global correction method, a novel approach for distortion correction is proposed which allows good image quality in relatively acceptable time by combining both global and local methods, and a new local interpolation method is also proposed. Computer simulation and experimental test on fluoroscopic image have been carried out. PMID- 17281718 TI - The application of quantitative ultrasound (QUS) on study of aging effects of achilles tendons. AB - Recently, the quantitative ultrasound (QUS) technique has been widely applied for the characterization of tissues. For example, it can be used for the quantization of Achilles tendons based on the broadband ultrasound attenuation (BUA) and speed of sound (SOS) when the ultrasound wave passes through the tissues. The main purpose of this study is to develop an integrated system to investigate the correlations between the measurements of Achilles tendons using QUS (UBIS 5000) and 2D ultrasound instrument (HDI 5000). Subjects including young (32 females and 17 males; mean age: 23.7+/-2.0) and middle-age groups (8 female and 8 males; mean age: 47.3+/-8.5 s) were recruited and tested for this study. All the subjects were ensured to have no habit of regular exercise and no record of tendon injury. The results show that BUA is significantly higher for the young group (45.2+/-1.6 dB/MHz) than the middle-age group (40.5+/-1.9 dB/MHz), while SOS is significantly lower for the young (1601.9+/-11.2m/s) than the middle-age (1624.1+/-8.7m/s). The thickness of Achilles tendons for both groups (young: 4.31+/-0.23mm; middle age: 4.24+/-0.23mm) are very similar. The noninvasive ultrasonic assessment of Achilles tendons might be helpful in clinical diagnosis and in evaluation of a therapeutic regimen. In the future, further animal studies should be made by measuring the BUA and SOS invasively to evaluate the accuracy of the parameters measured using QUS parametric images. PMID- 17281719 TI - A level set method for vessel segmentation in coronary angiography. AB - This paper presents a level set technique to extract the vascular structures in coronary angiography. It makes use of the Mumford-Shah functional to extract contours that are not necessary defined by gradient. A shape artery simulator was implemented to test and evaluate the detection method. Experimental results are presented on simulated data and real images successively. PMID- 17281720 TI - Medical image retrieval using salient point detector. AB - Salient or interest points ot a medical image can represent local properties of it. In this paper, a salient points based approach for medical image retrieval is proposed. In order to extract salient points from a medical image, we proposed a novel approach based on spectrum energy variation. Moreover, the other two salient points algorithm are also used. One is entropy-based and the other is a saliency-based bottom-up visual attention computational model which is motivated by visual physiological experimental results. Preliminary comparison study of salient points-based and entire image-based retrieval approach showed that our approach can achieve retrieval accuracy closely to global approach. Furthermore, amount of computation can be reduced by our approach. PMID- 17281721 TI - Ultrasonic liver characterization using phase congruency. AB - Feature extraction plays an important role in the whole process of liver characterization. Because the ultrasonic scanner in use can be adjusted by different clinicians to produce optimal images, the ultrasound images captured sometimes can be greatly influenced by machine settings and further impact the classification result. In this paper, some experiments are made to try to extract the liver features using the 2D phase congruency, which invariant to changes in intensity or contrast, to try to avoid those problems. The effectiveness of our method tested on three classes of liver images shows the potential for physicians to quantify liver status in clinical diagnosis. PMID- 17281722 TI - Study on scalable coding algorithm for medical image. AB - According to the characteristics of medical image and wavelet transform, a scalable coding algorithm is presented, which can be used in image transmission by network. Wavelet transform makes up for the weakness of DCT transform and it is similar to the human visual system. The second generation of wavelet transform, the lifting scheme, can be completed by integer form, which is divided into several steps, and they can be realized by calculation form integer to integer. Lifting scheme can simplify the computing process and increase transform precision. According to the property of wavelet sub-bands, wavelet coefficients are organized on the basis of the sequence of their importance, so code stream is formed progressively and it is scalable in resolution. Experimental results show that the algorithm can be used effectively in medical image compression and suitable to long-distance browse. PMID- 17281723 TI - A seepage flow model for vertebra CT image segmentation. AB - A seepage flow model for medical image segmentation has been presented, which linked to the natural phenomenon of "water seeks its own level". The seepage flow to form the segmented pixel set by submerging all the pixels that are r-connected to the initial spring head pixels and also fall within the submerging threshold limits, the moving water fronts keep adding to the segmented pixel set all the pixels until no more pixels fall within the submerging criterion. Based on Mumford-Shah function. A new merit function for criterion has been produced which possess two main kind of measurement reflecting the characteristic of region and contour respectively. Examples are presented to demonstrate the efficiency the model on clinical images segmentation. PMID- 17281724 TI - Study of image location for the high intensity focused ultrasound therapy system. AB - High intensity focused ultrasound (HIFU) is one of promising non invasive thermal ablation techniques of tumor, and the demand of imaging for guidance the HIFU procedure is becoming important. We choose ultrasound imaging method based on sequence images to locate the focal position of the HIFU. To the characteristic of ultrasound sequence images, we adopt a diffusion stick method for speckle noise suppression in ultrasonic images, and improve the discrete active contour method by adding external force in segmenting sequence ultrasonic images. The experiments of clinical ultrasonic images show that the techniques are effective. The next work is to reconstruct the processed sequence images into volume data for visualization and guidance the therapy procedure. PMID- 17281725 TI - Applications of pelvic 3D reconstruction and dimension measurement to colorectal cancer surgery. AB - Three-dimensional visualization is opening new worlds for more precise diagnosis and higher-quality treatment. 3D reconstruction from medical images is widely used in diagnosis and medical research. This paper focuses on 3D surface reconstruction of the pelvis from CT images on a personal computer. We measure and analyze large numbers of interrelated parameters in order to help doctor in diagnosis, operation planning and the actual surgery. PMID- 17281726 TI - Fractal feature extraction of marrow cell images. AB - An algorithm based on the cell image center of gravity and its scaleless range (as scale-invariant) is proposed to estimate the fractal dimension of the marrow cell images. Since the texture of a color image contains not only certain statistical similarity on the structure but also the color distributions, two color parameters are extracted from the color images of marrow cells for the fractal dimension calculation. An efficient approach is described for the discrimination between different marrow cells with the combination of the fractal dimension. PMID- 17281727 TI - Medical image registration by maximization of combined mutual information and edge correlative deviation. AB - A new approach of Medical Image Registration based on theories of mutual information and edge correlative deviation has been given in this paper. It takes advantage of the information contributed by the overall intensity values of original images as well as the correlation derived from the voxels' positions in edge images. It has been proven by tests that this new method inherits most merits of the former approaches and additionally bears several improved attributes: 1) The climaxes of parameters' curves are more obvious; 2) The errors are more diminished in extreme conditions where images lack intensity values; 3) It is more robust in resistance to aggravated white noise. PMID- 17281728 TI - Evaluating harris method in camera calibration. AB - In this paper, we focus on the performance of Harris feature point extraction method (Harris Method) and evaluate its characteristic in some aspects. We propose a set of criteria for the evaluation: Detection, Accuracy, Consistency, and Efficiency. All of these criteria are defined theoretically and measured with different kinds of images. Especially, to verify the localization accuracy of Harris Method, we synthesize a series of chessboard images in which the real coordinates of feature points could be computed. Therefore, the criteria proposed here are objective and believable. PMID- 17281729 TI - A weighted sum of multi-scale Gaussians generates new near-ideal interpolation functions. AB - Interpolation is a very important technique in medical image processing. Of the different generations of interpolation kernels, the one using combinations of Gaussians and its partial derivatives, is locally compact, has excellent Fourier properties and is easy to handle analytically. But the dc-constancy behaviour i.e. the sum of the samples of these Gaussian kernels is not necessarily one and also the zero-crossings do not fit exactly. These deviations from the ideal behaviour contribute to artifacts during interpolation. We propose in this article a novel approach for the generation of kernels from the combinations of Gaussians at different scales. We will show that these kernels are locally compact, have excellent Fourier properties and the zero-crossings fit exactly. The DC-constancy behaviour is better than those reported. It has been shown that the proposed kernels are likely to be very useful in medical images. PMID- 17281730 TI - Preliminary application of neural network in differentiating benign from malignant solitary pulmonary nodule on HRCT. AB - In this study, the performance of artificial neural network (NN) in diagnosis of solitary pulmonary nodule (SPN) on HRCT images was evaluated. One hundred and forty-five cases of SPN, including 86 cases of pulmonary carcinoma, 18 cases of tuberculoma, 29 cases of inflammatory nodule and 12 cases of benign tumor, were collected, which were all confirmed by pathology or biopsy and over-two-year clinical treatment. Five clinical parameters and 10 radiological characteristics were observed and quantified for qualitative characteristics. About 70 percent of all cases (up to 103 cases) were selected randomly to form training samples set, on which BP neural network and Logistic regression model were built. The total consistent rate 98.6% of BP NN was greater than that of Logistic model, which is 88.3% (P=0.0007). Areas under ROC curve were 0.997+/- 0.004 and 0.959+/-0.016 respectively, and the difference between the two was significant statistically (P=0.009). NN showed high performance in diagnosis of SPN on HRCT images. It was worthy of further study. PMID- 17281731 TI - Automatic labelling and BI-RADS characterisation of mammogram densities. AB - Intelligent management of medical data is an important field of research in clinical information and decision support systems. Such systems are finding increasing use in the management of patients known to have, or suspected of having, breast cancer. Different types of breast-tissue patterns convey semantic information which is reported by the radiologist when reading mammograms. In this paper, a novel method is presented for the automatic labelling and characterisation of mammographic densities. The presented method is first concerned with the identification of the prominent structures in each mammogram. Subsequently, "dense tissue" is labelled in a mammogram data set, and BI-RADS classification is performed based on a 2D pdf that is contracted from a "ground truth" data set as well as a shape analysis framework. The presented method can be used in large-scale epidemiological studies which involve mammographic measurements of tissue-pattern, especially since breast-tissue density has been linked to an increased risk of breast cancer. PMID- 17281732 TI - Features of central projection average difference function for skull recognition. AB - The recognition technology based on biological feature is a hot topic in recent years, and the recognition technology concerning the skull features was studied in this paper. The central projection transform about the two-dimension skull image was performed, the central projection function of the gray value was obtained, the average difference function of the central projection value and it's vectors were defined, and the research on the vector feature of the average difference function was carried out. This feature is robust in noisy backgrounds, less calculation consuming, and it can also be used to recognize other objects. PMID- 17281733 TI - A hierarchical elastic registration scheme based on deformable segmentation. AB - In this paper a hierarchical scheme is presented for contour-based elastic image registration. An improved deformable model is used to simultaneously segment and register feature from multiple images. The objects in different images are segmented by evolving a single contour and meanwhile the parameters of affine registration transformation are found out. After that, a contour-constrained elastic registration is applied to register the images correctly. The experimental results indicate that the proposed approach is effective to segment and register medical images. PMID- 17281735 TI - Extraction of brain tumor from MR images using one-class support vector machine. AB - A novel image segmentation approach by exploring one-class support vector machine (SVM) has been developed for the extraction of brain tumor from magnetic resonance (MR) images. Based on one-class SVM, the proposed method has the ability of learning the nonlinear distribution of the image data without prior knowledge, via the automatic procedure of SVM parameters training and an implicit learning kernel. After the learning process, the segmentation task is performed. The proposed technique is applied to 24 clinical MR images of brain tumor for both visual and quantitative evaluations. Experimental results suggest that the proposed query-based approach provides an effective and promising method for brain tumor extraction from MR images with high accuracy. PMID- 17281734 TI - Analysis of retinal images associated with hypertension and diabetes. AB - Twenty four retinal images from three groups, normotensivel, hypertension and diabetes, were analyzed. The features were extracted, including exudates, bifurcation angle, artery-to-veins diameter ratio, mean artery and veins diameters, form and size of optic disc, and vessel tortuosity. The results showed that exudates appeared in both hypertensive and diabetic groups. For hypertensive group, exudates increased with the years of illness. There was no relationship between exudates and years of illness for diabetic group. No significant changes in the first bifurcation angle among three groups were observed. The mean arterial diameter tended to decrease for hypertensive and diabetic groups while the mean veinal diameter dilated. Compared to the normotensive group, the ratio of arterial diameter to veinal diameter decreased for both hypertensive and diabetic group. The form and size changes of the optic disc were obvious in diabetic group. Hypertensive group showed tortuous blood vessels. No tortuous blood vessels were observed in the diabetic group. The study demonstrated that it is feasible to use automatically generated retinal image features as an effective screening method for detection of hypertension and diabetes. PMID- 17281736 TI - Research on features of retinal images associated with hypertension and diabetes. AB - In order to discussed the feasibility of detecting hypertension and diabetes using certain features of retinal images, this paper compared features of Twenty six retinal images from three groups, normotensive, hypertension and diabetes Those features including exudates, bifurcation angle, artery-to-veins diameter ratio, mean artery and vein diameters, shape and size of optic disc, and vessel tortuosity. The results show that in retinal images of hypertension and diabetes, exudates appeared, and the area increased with years of illness. The mean arterial diameter tended to decrease while the mean vein diameter dilated. Compared to the normotensive group, the artery-to-vein diameter ratio decreased for both the hypertensive and diabetic group. The shape and size changes of the optic disc were obvious in the diabetic group. The hypertensive group showed tortuous blood vessels. No tortuous blood vessels were observed in the diabetic group. The study demonstrates that, expect the bifurcation angles, it is unfeasible to use retinal image features in the detection of hypertension and diabetes, but they do have some meaning in clinic diagnosis of hypertension and diabetes since some characteristics of retinal images of those patients become pathologically changed. PMID- 17281737 TI - A statistical comparison of digital X-Ray images for MTB patients. AB - A common practice in medical diagnosis and patient management is the comparison of two chest radiographs images. The difference between two digital images at two time points is a measure of the effect of treatment on the patient. Two measures of similarity, the ordinary regression coefficients, R(s)(2) and coefficients of determination for the Unreplicated linear functional relationship model (ULFR), R(f) (2), are used to compare images for the particular case of Mycobacterium Tuberculosis (MTB). Our results suggest that a series of R2 values indicates gradual declining trends with values falling within a band. New patients with a series of R2 values falling within this band may be consider as making a good or acceptable recovery. PMID- 17281738 TI - Computer assisted solitary pulmonary nodules morphological enhancement characteristics - a preliminary study. AB - The quantity analysis on Solitary Pulmonary Nodules (SPN) is very important for pulmonary disease diagnosis and prediction, especially, in the early phase or small sizes. Due to the breathing activity of patients, the SPN region is translated and deformed after the injection of bolus so that it is hard to obtain the exact enhancement patterns. In this presentation, we give an approach to combine plain CT images and enhanced CT images to assist the radiologists in SPN diagnosis or prediction. First we segmented SPN region in both the plain image and the enhanced image, then rigid and deformable registration method were carried out to match the enhanced SPN region to the plain SPN region, then we subtracted the SPN region from the enhanced SPN region to show the enhancement, finally we correlated the enhancement characteristics with corresponding diagnosis results. PMID- 17281740 TI - Ultrasound speckle suppression and edge enhancement using multiscale nonlinear wavelet diffusion. AB - This paper introduces a novel multiscale nonlinear wavelet diffusion (MNWD) method for ultrasound speckle suppression and edge enhancement. It considers wavelet diffusion as an approximation to nonlinear diffusion within the framework of the dyadic wavelet transform. Consequently, this knowledge is exploited in the design of a speckle suppression filter with an edge enhancement feature. MNWD takes advantage of the sparsity and multiresolution properties of wavelet, and the iterative edge enhancement feature of nonlinear diffusion. In our algorithm, speckle is suppressed by employing the iterative multiscale diffusion on the wavelet coefficients, while the edges of the image are enhanced by using an iterative signal compensation process. We validate the proposed method using synthetic and real echocardiographic images. Performance improvement over other traditional denoising filters is quantified in terms of noise suppression and structural preservation indices. The application of the proposed method is demonstrated by the segmentation of the echocardiographic image using the active contour. PMID- 17281739 TI - Automated matching of genomic structures in microscopic images of living cells using an information theoretic approach. AB - Advances in microscopic imaging technology have revolutionized biology in recent years by enabling the study of dynamic processes inside living cells. Time-lapse microscopy produces large numbers of sequential images of living cells taken over time. In this paper we describe the novel approaches we have developed to automate and introduce high accuracy to the process of identifying genomic structures in living cells and matching them between consecutive time-points. We derive control points from landmarks within the structures and use the Kulback Leibler divergence as an information-theoretic approach to correctly resolve potential close matches within the iterative closest point (ICP) algorithm. We also describe the steps needed to extend our techniques to analyze three dimensional voxel images. The approaches we describe are widely applicable in the analysis of timelapse microscopy data. PMID- 17281741 TI - Measurement of ocular torsion using iterative Lucas-Kanade optical flow method. AB - This paper presents a new method for measuring ocular torsion using the optical flow. Iris image is cropped and transformed into rectangular image to make a orientation invariant image. Feature points were selected at iris region from a reference and a target image, and then shift of each feature was calculated using iterative Lucas-Kanade method. The feature points were selected according to the strength of corner on the iris image. The accuracy of the algorithm was tested using printed eye image and compared with traditional cross-correlation method. Measurement error was less than 0.15 degree. PMID- 17281742 TI - Designing a low-cost mattress sensor for automated body position classification. AB - Determination of body position on a mattress in a clinical setting is important for both diagnosis of sleep disorders and management and prevention of pressure sores. At present, patient body position is measured by visual inspection or by post analysis of either a video monitoring system or expensive, high-resolution arrays of pressure sensors. Due to the high cost and time consumption, often the alternative, a set of accelerometers tethered to the patient is used. However, these accelerometers only provide directional orientation of the patient torso, and yield little information regarding the total body position. We present in this paper a design for a low-cost sensor mat that combines a minimum number of sensors with a feed-forward neural net for autonomous detection and distinction of body position into a set of discrete patterns. PMID- 17281743 TI - Clinical content detection for medical image retrieval. AB - Content-based image retrieval (CBIR) is the most widely used method for searching large-scale medical image collections; however this approach is not suitable for high-level applications as human experts are accustomed to manage medical images based on their clinical features rather than primitive features. Automatic detection of clinical features in a large-scale image database and realization of image retrieval by clinical content are still open issues. This paper presents a Markov random field (MRF) based model for clinical content detection. Multiple classifiers are applied to recognize a wide range of clinical features in a large scale histological image database, and they are further combined to generate more reliable and robust estimation. Spatial contexts will cooperate with local estimations in the MRF based model to make a decision based on global consistency. The detected clinical features will provide a basis for image retrieval. Experiments have been carried out in a large-scale histological image database with promising results. PMID- 17281744 TI - Ultrasound image compounding based on motion compensation. AB - The quality of ultrasonic images is usually influenced by speckle noises. To reduce the speckle noise, compounding techniques have been widely applied to improve image quality through signal averaging. In this paper, a 2-D ultrasonic motion compounding system is proposed that uses a hierarchical adaptive feature weighted motion estimation method to realign the frames before compounding. Each frame is first registered to the reference frame and then compounded to reduce the speckle noises. Several compounding strategies are then used to remove the unwanted degradation. Performance has been tested on both synthetic and in vivo clinical ultrasonic images. The experimental results show that the motion can be assessed accurately and the compounded images achieve good signal-to-noise ratio for improving the quality of ultrasonic images. PMID- 17281745 TI - Effect of CT Image-Based Voxel Size On Monte Carlo Dose Calculation. AB - Currently, the conventional empirical or semi-empirical dose calculation algorithms for radiation treatment planning system have been selected as dose engines. The accuracy of these dose calculation algorithms is limited. The main problem is that they fail to adequately consider the lateral transport of radiation or loss of electronic equilibrium near interface between two heterogeneous mediums. Monte Carlo method provides a kind of precise and general solution to photon and electron dose calculation problem, but the puzzle of the longer CPU time affects its clinical application finally. The Monte Carlo code system (EGSnrc) has been used to investigate the different voxel sizes effect on the accuracy of dose distributions and computing time in the present paper. Based on a patient head and neck CT data case studied, it may be concluded that less than 4mm voxels should be used for Monte Carlo dose calculations to insure the superior accuracy of dose distribution, higher image resolution and shorter CPU time. PMID- 17281746 TI - Prediction of scoliosis progression in time series using a hybrid learning technique. AB - Scoliosis is a common and poorly understood spinal disorder that is clinically monitored with a series of full spinal X-rays. The purpose of this study was to predict scoliosis future progression at 6- and 12-month intervals with successive spinal indices and a hybrid learning technique (i.e., the combination of fuzzy c means clustering and artificial neural network (ANN)). Ultimately this could decrease scoliotic patients' radiation exposure and the associated cancer risk in growing adolescents. Seventy-two data sets were derived from a database of 56 acquisitions from 11 subjects (29.8 +/- 9.6 degrees Cobb angle, 11.4 +/- 2.4 yr), each consisting of 4 sequential values of Cobb angle and lateral deviations at apices in 6- and 12-month intervals in the coronal plane. Progression patterns in Cobb angles (n = 10) and lateral deviations (n = 8) were successfully identified using a fuzzy c-means clustering algorithm. The accuracies of the trained ANN, having a structure of three input variables, four nonlinear hidden nodes, and one linear output variable, for training and test data sets were within 3.64 degrees (+/- 2.58 degrees) and 4.40 degrees (+/- 1.86 degrees) of Cobb angles, and within 3.59 (+/-3.96) mm and 3.98 (+/- 3.41) mm of lateral deviations, respectively. Those results were twice the accuracy of typical clinical measurement (~10 degrees) and in close agreement with those using cubic spline extrapolation and adaptive neuro-fuzzy inference system (ANFIS) techniques. The adapted technique for predicting the scoliosis deformity progression holds significant promise for clinical applications. PMID- 17281747 TI - A new algorithm for watershed segmentation of cells in marrow. AB - A new watershed segmentation algorithm of binary images based on the convex property of cells is proposed in this study. A distance map is developed to determine the number of seeds due to iterative erosion. The ultra-erosion aggregate is considered as seeds to separate the cell cluster, and images are grown by dilation from these seeds until all the image pixels are assimilated except the convex boundary. In order to speed up the computation while maintaining a good cell contour, the choice and growing of seeds are under control. PMID- 17281748 TI - Presentation and validation of an accurate and effective segmentation for dynamic heart modeling. AB - An accurate and effective segmentation technique is the basis of the ideal dynamic heart modeling. In this paper, a novel multistage approach is proposed to perform the segmentation for the heart modeling and its multistage segmentation procedure orderly consists of four stages: Morphological Recursive Erosion (MRE); Fast Marching (FM); 3D Morphological Reconstruction (MR) and Morphological Recursive Dilation (MRD). To prove its accuracy and effectiveness, the approach is tested on 3 CT datasets of beating heats with each set containing ten individual volumes throughout a cardiac cycle. In order to validate the segmentation results, a novel Ra0dial Distance Based Validation (RDBV) method is also presented in this paper that provide the Global Accuracy (GA) measure to evaluate the segmentation accuracy. GA is calculated based on a Local Radial Distance Error (LRDE), which is along the radii emitted from the points along the skeleton of the object, to accommodate the complicated cardiac structure. The RDBV is improved in the universality and ability to reflect significant local errors in global accuracy function. The average accuracy of the proposed segmentation approach using the RDBV is 0.783. PMID- 17281749 TI - Image segmentation based on random neural network model and Gabor filters. AB - Image segmentation is a fundamental image process technique and plays an essential role in ultrasound image analysis. In this article, we propose an algorithm for image segmentation which is based on the random neural network (RNN) and features extracted by a bank of Gabor filters. With the scientists' work, it is revealed that Gabor functions act as some functions of human vision. And the RNN model proposed by Gelenbe is closer to biophysical reality and mathematically more tractable, in which signals in the form of impulses are transmitted with a certain probability. The segmentation algorithm based on these two techniques provide a good distinguish and classification capability for textures in the image. Furthermore, a strategy which is named as quartered segmentation strategy is also presented here in order to reduce the computation and speed up our approach. The presented algorithm is tested on an image produced by using Brodatz album and an ultrasound image, and the results are promising. PMID- 17281751 TI - Linear models of cumulative distribution function for content based medical image retrieval. AB - We propose an Image matching method based n Cumulative Distribution Function (CDF). The CDF f the query and database Images are approximated by piecewise linear models with two parameters, slope and intercept at various grayscale intervals. The equations solving the least squares line fitting algorithm are very simple to form, due to closed form expressions The contiguous set of lines approximating the CDFs enables us to compare query and database images with corresponding estimated slopes and intercepts. As the dynamic range f CDF is from 0 to 1, images of different sizes can be compared. Approximation of CDFs with lines further reduces the dimension f the image features and thus improves the speed f matching. Also, the monotonically increasing CDF is well suited for approximations with lines. Resolving the CDF with lines f different lengths recasts the matching to a hierarchical methodology. PMID- 17281750 TI - CULEX-completely user-independent layers extraction: ultrasonic carotid artery images segmentation. AB - The analysis of the carotid wall is of paramount importance in clinical practice. In fact, the intima-media thickness is a risk index for some of the most severe acute cerebrovascular pathologies; hence, the need for an accurate segmentation of the different layers of the carotid artery. In the past ten years, a wide variety of algorithms for the carotid tunica segmentation have been proposed, but they require a certain degree of user interaction. In this paper we propose a novel approach to the completely user-independent segmentation of the carotid artery wall. Our algorithm has been designed for the extraction of the intima and media layers of the distal carotid wall, based on ultrasonic B-Mode images. We evaluated the performance of the algorithm on a set of 63 images and compared the automatic segmentation to that traced by a trained operator. We obtained a mean error lower than 1.3 pixel both on the intima and media layers, which is comparable to that obtained by means of operator dependent techniques. PMID- 17281752 TI - White blood cell image segmentation using on-line trained neural network. AB - This paper addresses a fast white blood cell (WBC) image segmentation scheme implemented by on-line trained neural network. A pre-selecting technique, based on mean shift algorithm and uniform sampling, is utilized as an initialization tool to largely reduce the training set while preserving the most valuable distribution information. Furthermore, Particle Swarm Optimization (PSO) is adopted to train the network for a faster convergence and escaping from a local optimum. Experiment results show that under the compatible image segmentation accuracy, the training set and running time can be reduced significantly, compared with traditional training methods. PMID- 17281753 TI - Improved segmentation of ultrasound brain tissue incorporating expert evaluation. AB - The quantitative analysis of medical ultrasound images for the purpose of diagnosis is a difficult task due to the speckle noise present in the images. Nowadays medical doctors depend strongly on the visual interpretation of the images which is subjective to some account. Trying to reduce this noise should assist the experts in a better understanding of some pathologies. We focus on a brain disease called periventricular leukomalacia, also called white matter damage, which occurs frequently on premature neonates. For the moment the affected brain tissue is segmented semi-automatically using two different techniques that take the speckle noise into little account. Here we propose a framework which includes an efficient preprocessing step and relying on expert based evaluation we develop an integrated segmentation method, which yields a more accurate and better reproducible segmentation. PMID- 17281754 TI - Adaptive successive erosion-based cell image segmentation for p53 immunohistochemistry in bladder inverted papilloma. AB - Cell nuclei segmentation is a critical issue in automatic cell analysis for cancer diagnosis and prognosis. Marker-controlled watershed segmentation algorithm is used the most commonly. In this paper, adaptive successive erosion based (ASE) marker extraction method for watershed algorithm is presented, with the goal of extracting markers labelling each individual nucleus, including overlapping cell nuclei. Based on the new marker detection method, an integrated cell image segmentation algorithm is developed for p53 immunohistochemistry in bladder inverted papilloma. Experiments were performed on a number of images, and results demonstrate that the algorithm produces more accurate segmentation than other methods. PMID- 17281755 TI - A knowledge-based fuzzy clustering method with adaptation penalty for bone segmentation of CT images. AB - Accurate segmentation is critical in many advanced imaging applications such as volume determination, radiation therapy, 3D rendering, and surgery planning. However, due to the complex anatomical structure of tissue and organs, as well as artifacts caused by patient motion, beam hardening, and partial volume effect in CT image, the boundaries between different regions are smeared. In addition, the intensities of bone voxels vary widely that some of them are so close to that of the muscle. They all make the extraction of bone out of surrounding tissue quite difficult in CT images. In this study, a knowledge-based fuzzy clustering method was proposed, which was formulated by modifying the objective function of the standard fuzzy c-means (FCM) algorithm with additive adaptation penalty. Since the membership of voxels in boundary regions is intrinsically fuzzy, unsupervised fuzzy clustering methods turns out to be particularly suitable for handling the bone segmentation problem. The knowledge-based fuzzy clustering method was tested by patient CT images. Experimental results demonstrated that while the conventional FCM methods might loss a significant amount of bone volume during segmentation, the proposed method could improve the performance of bone extraction significantly. PMID- 17281756 TI - Medical images edge detection based on mathematical morphology. AB - Medical images edge detection is an important work for object recognition of the human organs and it is an important pre-processing step in medical image segmentation and 3D reconstruction. Conventionally, edge is detected according to some early brought forward algorithms such as gradient-based algorithm and template-based algorithm, but they are not so good for noise medical image edge detection. In this paper, basic mathematical morphological theory and operations are introduced at first, and then a novel mathematical morphological edge detection algorithm is proposed to detect the edge of lungs CT image with salt and-pepper noise. The experimental results show that the proposed algorithm is more efficient for medical image denoising and edge detection than the usually used template-based edge detection algorithms and general morphological edge detection algorithms. PMID- 17281757 TI - Geometric active contour model with color and intensity priors for medical image segmentation. AB - A new algorithm by using geometric active contour model with the fusion of color and intensity priors to segment medical images has been presented in this paper. The prior knowledge used here are firstly defined in different color spaces and represented as thresholds searched by genetic algorithm. Then the prior knowledge is merged into active contour model with its contour evolution by the level set technique. The experiments on clinical marrow images and mammograms have successfully demonstrated its superiority of the proposed algorithm over the existing active contour models, which deal with image gradient information. PMID- 17281758 TI - Segmentation of the breast region in mammograms using watershed transformation. AB - The author proposes a new approach for the breast region segmentation for the purpose of reduction of subsequent processing calculation and removal of radiopaque artifacts. The proposed algorithm combines the global thresholding method for a coarse estimation of breast region and morphological operations for exact positioning of the breast boundary. 204 mammographic images were randomly selected from the DDSM mammogram database to test the segmenting algorithm and the segmentation results were evaluated by an experienced radiologist. Nearly 95% of the segmentation results were rated as exact segmentation. PMID- 17281759 TI - A novel iris localization algorithm based on the gray distributions of eye images. AB - In this paper, we proposed a novel iris localization algorithm based on the gray distributions of eye images. Firstly, according to the gray features, find a point inside the pupil using a gray value summing operator. Next, starting from this point, find three inner boundary points using a boundary detection template, and then calculate the circle parameters of inner boundary according to the principle that three points which are not on the same line can define a cricle. Finally, find three iris outer boundary points utilizing the similar algorithm and obtain the circle parameters. A large number of experiments on the CASIA iris image database demonstrated that the localization results of proposed algorithm are more accurate and more rapid than any other classical algorithms, such as Daugman's algorithm and Hough transform. PMID- 17281760 TI - A combining method for tumors detection from near-infrared breast imaging. AB - This paper introduces the new qualitative and quantitative methods, which can diagnose breast tumors. Qualitative methods include blood vessel display inside and outside of pathological changes part of breast, display of equivalent pixel curves at the part of pathological changes and display of breast tumor image edge. Accordingly, three feature extraction operators are proposed, i.e. the combination operators of anisotropic gradient and smoothing operator, an improved Sobel operator and an edge sharpening operator. Furthermore, quantitative diagnose approaches are discussed based on blood and oxygen contents according to abundant clinical data and pathological mechanism of breast tumors. The results of clinic show that the methods of combining qualitative and quantitative diagnose are effective for breast tumor images, especially for early and potential breast cancer. PMID- 17281761 TI - An improved electronic colon cleansing method for detection of polyps by virtual colonoscopy. AB - Electronic colon cleansing (ECC) aims to segment the colon lumen from the patient abdominal image acquired with colonic material tagging by oral contrast and other means, so that a virtual colon model can be constructed. Virtual colonoscopy (VC) navigates through the colon model looking for polyps in a similar manner as the fiber optic colonoscopy does. We had built an ECC pipeline for the commercial VC system of Viatronix Inc. In this paper, we present an improved ECC method. It is based on a partial -volume image -segmentation framework, which is derived using the well-established statistical expectation-maximization algorithm. The presented ECC method was evaluated by both visual inspection on the cleansed colon lumens and computer-aided detection of polyps (CADpolyp) using 20 patient datasets. Compared to our previous ECC pipeline, this presented new method demonstrates improvement in both visual judgment and CADpolyp. PMID- 17281762 TI - Automated detection of optic disk boundary by a new deformable model technique. AB - A new algorithm to detect the exact optic disk boundary, based on deformable model, is proposed in this paper. The energy function for deformation is defined as a combination of local energies. The proposed method modified the original snake technique in two aspects: clustering the contour points into edge-point group or uncertain-point group after each deformation, and updating the contour by variable updating-sample numbers. The modifications not only directly solve the blood vessel problem, but also make this algorithm more accurate and robust to noises, weak edges and fuzzy contour shapes. Based on 100 randomly-selected testing images, the success rates are 94% for the proposed method, as compared to 12% for the GVF-snake and 82% for the modified ASM algorithm, which show the effectiveness of the proposed method. PMID- 17281763 TI - A Study of observation system of time-sequenced images of multi-sliced CT based on a PC. AB - We developed a method for an observation system of time-sequenced images of heart, vessels, and surrounding organs. The observation images are constructed using multi-sliced CT tomogram images by applying texture mapping technology, one of which is namely 3D-pseudo solid image. The generated images could be observed like as a solid modeled image and be generated faster than by using solid model. The method can be realized on a contemporary PC (which means movable) and also applicable to be a part of the intuitive observation system developed already. PMID- 17281764 TI - Feature and knowledge based analysis for reduction of false positives in the computerized detection of masses in screening mammography. AB - Previously we presented a morphologic concentric layered (MCL) algorithm for the detection of masses in screening mammograms. The algorithm achieved high sensitivity (92%) but it also generated 3.26 false positives (FPs) per image. In the present study we propose a false positive reduction strategy based on using an artificial neural network that merges feature and knowledge-based analysis of suspicious mammographic locations. The ANN integrates two types of information regarding the suspicious candidates: (i) directional and fractal neighborhood analysis features, and (ii) knowledge-based analysis using an information theoretic similarity metric. The study hypothesis is that the synergistic application of feature and knowledge-based analysis will be an effective strategy to reduce false positives while still maintaining sufficiently the detection rate for true masses. The study was performed using mammograms from the Digital Database of Screening Mammography. Using the fusion ANN decision strategy 56% of the FPs were reduced while maintaining 95% of the true masses. PMID- 17281765 TI - Tumor detection using airways asymmetry. AB - A novel tumor detection technique on CT Scan images of the neck area is detailed in this paper. This technique is based on an airways' symmetry evolution within slices. The algorithm proposes to the physician a set of three slices where a tumor (if it exists) should mostly be located. Then, he will just have to browse the three slices instead of almost 100 in a CT scan. Our method is very effective and shows no false alarms within the patients in our database. In each of our tests the tumors were found to be close to one of the three proposed slices. PMID- 17281766 TI - A comparison of feature selection methods for the detection of breast cancers in mammograms: adaptive sequential floating search vs. genetic algorithm. AB - This paper presents a comparison of feature selection methods for a unified detection of breast cancers in mammograms. A set of features, including curvilinear features, texture features, Gabor features, and multi-resolution features, were extracted from a region of 512x512 pixels containing normal tissue or breast cancer. Adaptive floating search and genetic algorithm were used for the feature selection, and a linear discriminant analysis (LDA) was used for the classification of cancer regions from normal regions. The performance is evaluated using Az the area under ROC curve. On a dataset consisting 296 normal regions and 164 cancer regions (53 masses, 56 spiculated lesions, and 55 calcifications), adaptive floating search achieved Az = 0.96 with comparison to Az = 0.93 of CHC genetic algorithm and Az = 0.90 of simple genetic algorithm. PMID- 17281767 TI - A novel eyelash detection method for iris recognition. AB - Iris is often affected by the eyelash noise, when captured under unfavorable condition. Not only the iris localization of inner and outer boundaries, but also iris feature extraction can be affected by eyelash. Therefore, in an iris recognition system, eyelash detection is of great importance for accurate iris recognition. Eyelash can be classified into two classes: (1) separable eyelashes (2) multiple eyelashes. The former are detected by local intensity minimum algorithm, and the latter are detected according to the template mean and standard deviation. Experimental results show that the proposed method can detect eyelash accurately. PMID- 17281768 TI - Recognition mechanism of a neural network for character recognition. AB - We have developed a small scale four-layered neural network (NN) model for simple character recognition, which can recognize the patterns transformed by affine conversion. In this study 24 patterns are presented as input patterns. An input pattern is divided into 64 local patterns and connected with the 1st hidden layer. After the training, we investigated the recognition mechanism of NN using Alopex algorithm. Effectiveness of this method is demonstrated. PMID- 17281769 TI - Distinguishing electroporation from thermal injuries in electrical shock by MR imaging. PMID- 17281770 TI - Synthesis of a functional information with anatomical landmarks by multiresolution fusion of brain images. AB - In order to help clinicians with the diagnosis of neurodegenerative diseases, we provide a synthetic functional information located in relation with anatomical structures. The final image is processed by multimodal data fusion between SPECT and MR images. We propose a new method for the management of such multiresolution data, in which a geometrical model allows an accurate correspondence of voxels from both images, while preserving at best both original pieces of information. We use this matching method to replace the interpolation step in the compulsory image registration of the data fusion process. The geometrical model is first built from registration parameters. Computational geometry algorithms, applied to this model, allow the computation of numerical values used to process the final information. The method has been applied to brain perfusion and neurotransmission SPECT images. PMID- 17281771 TI - Endoscopy imaging intelligent contrast improvement. AB - In this paper, we present a medical endoscopy video contrast improvement method that provides intelligent automatic adaptive contrast control. The method fundamentals are video data clustering and video data histogram modification. The video data clustering allows an effective use the low noise two channel contrast enhancement processing. The histogram analysis permitted to determine the video exposure type for simple and complicated contrast distribution. We determined the needed gamma value for automatic local area contrast improvement for the following exposure types: dark, normal, light, dark light, dark normal etc. The experimental results of medical endoscopy video processing allow defining the automatic gamma control range from 0.5 to 2.0. PMID- 17281772 TI - An adaptive denoising method based on local mode estimation. AB - An adaptive method is presented in this paper to cope with gaussian noise through local structure estimation. Even regions and uneven regions are distinguished firstly, then each uneven region is further segmented into two subregions by fuzzy c-means clustering algorithm and fisher discriminant analysis. Finally, linear approximation is used to estimate the intensities of each region. With the introduction of local structure analysis, gaussian noise is reduced effectively with edges preserved very well. Experimental results also demonstrate its effectiveness in terms of medical images enhancement, while it is also applicable to other similar images that have many tiny details. PMID- 17281774 TI - Visible Korean human. improved serially sectioned images of the entire body. AB - The data from the Visible Human Project (VHP) and the Chinese Visible Human (CVH), which are the serially sectioned images of the entire cadaver, are being used to produce three-dimensional (3D) images and software. The purpose of our research, the Visible Korean Human (VKH), is to produce an enhanced version of the serially sectioned images of an entire cadaver that can be used to upgrade the 3D images and software. These improvements are achieved without drastically changing the methods developed for the VHP and CVH; thus, a complementary solution was found. A Korean male cadaver was chosen without anything perfused into the cadaver; the entire body was Magnetic Resonance (MR) and Computed Tomography (CT) scanned at 1.0 mm intervals to produce MR and CT images. After scanning, entire body of the cadaver was embedded and serially sectioned at 0.2 mm intervals; each sectioned surface was inputted into a personal computer to produce anatomical images (pixel size: 0.2 mm) without any missing images. Eleven anatomical organs in the anatomical images were segmented to produce segmented images. The anatomical and segmented images were stacked and reconstructed to produce 3D images. The VKH is an ongoing research; we will produce a female version of the VKH and provide more detailed segmented images. The data from the VHP, CVH, and VKH will provide valuable resources to the medical image library of 3D images and software in the field of medical education and clinical trials. PMID- 17281773 TI - Application of the laguerre deconvolution method for time-resolved fluorescence spectroscopy to the characterization of atherosclerotic plaques. AB - This study investigates the ability of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) to detect inflammation in atherosclerotic lesion, a key feature of plaque vulnerability. A total of 348 TR-LIFS measurements were taken from carotid plaques of 30 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified as Early, Fibrotic/Calcified or Inflamed lesions. A stepwise linear discriminant analysis algorithm was developed using spectral and TR features (normalized intensity values and Laguerre expansion coefficients at discrete emission wavelengths, respectively). Features from only three emission wavelengths (390, 450 and 500 nm) were used in the classifier. The Inflamed lesions were discriminated with sensitivity > 80% and specificity > 90 %, when the Laguerre expansion coefficients were included in the feature space. These results indicate that TR LIFS information derived from the Laguerre expansion coefficients at few selected emission wavelengths can discriminate inflammation in atherosclerotic plaques. We believe that TR-LIFS derived Laguerre expansion coefficients can provide a valuable additional dimension for the detection of vulnerable plaques. PMID- 17281775 TI - A new hybridized rigid-elastic multiresolution algorithm for medical image registration. AB - We present a new hybridized rigid-elastic multiresolution algorithm of registration for medical image. The rigid deformation is achieved by a global affine transformation function composed of B-spline, in which the knots of B spline are the four vertexes of the medical image. If we increase the quantity of the knots of the B-spline along the X and Y coordinates axes, the deformation function will be more complex and "elastic", which can complete elastic matching to align the local deformation in the medical image. In 16 groups of contrast tests, the hybridized algorithm achieves a total accuracy rate of 81.25%, while Kybic's elastic algorithm only achieves a total accuracy rate of 31.25%. It is proved that the hybridized algorithm is more robust than Kybic's elastic algorithm of registration. PMID- 17281776 TI - Color compensation for anomalous trichromats based on error score of FM-100 Hue test. AB - In this paper, we propose novel color compensation for anomalous trichromat. The proposed method is to compensate colors defected due to anomalous trichromacy. The proposed color compensation is performed with color deficiency degree measured by total error score of FM-100 Hue test. The relationship between the deficiency degree and color variation is modeled for accurate compensation. Clinical experiments were performed and the results verified the proposed compensation method. PMID- 17281777 TI - A real-time display method for ultrasound color flow velocity estimation. AB - This paper proposes a new way for ultrasound color flow velocity estimation and display. This method sets up a mapping table which directly relates to the dynamic range of the velocity display by using an inverse mapping instead of calculating the arctangent value directly. This method is ideal for software implementation and offers an interactive way to user for changing the dynamic range of flow velocity to increase the display resolution. PMID- 17281778 TI - Kernel regularized bone surface reconstruction from partial data using statistical shape model. AB - This paper addresses the problem of surface reconstruction from partial data consisting of digitized landmarks and surface points that are obtained intraoperatively. The surface is derived by deforming a template so that the reconstructed surface matches the digitized points. Two techniques are employed to address such an ill-posed problem. First, a patient-specific template is used, which is computed by optimally fitting a statistical deformable model to partial data. Second, the estimated patient specific template is deformed using a regression technique by carefully designing a regularization term in kernel space. The proposed method is especially useful for accurate and stable surface construction from partial data when only a small sample size of training set is available. It adapts gradually to use more information derived from the statistical shape model when larger data are available. The proposed reconstruction method has been successfully tested on femoral heads, yielding very promising results. PMID- 17281779 TI - Registration of ultrasonic cardiac images. AB - We describe an efficient approach to the registration problem of ultrasonic cardiac images using an affine transformation model, incorporating a mutual information based error minimisation. The affine motion model provides an analytic solution which has fast and stable convergence. The geometric and intensity constancy constraint is combined with the smoothness constraint, which allow us to have approximate image alignment. Due to complexity of a realistic motion, we then minimise the error in intensity between the registered source and the target image in the context of mutual information. In fact, image registration can be reached when the amount of information buried in the images is maximised. The experimental results demonstrate that this hybrid framework is highly efficient in registering different cardiac images. PMID- 17281780 TI - Nonlinear diffusion, negentropy and restoration of mammographic images. AB - Diffusive iterative filtering may be used to restore mammographic noisy images. Assuming that images are corrupted by additive gaussian noise, the negentropy as a statistical measure of the nongaussianity, can be used to estimate the amount of noise removed from noisy images. In particular, the evolution of the negentropy with the iterations is used to introduce a stopping criterion to end the diffusive filtering process. Because of computational complexity of the negentropy function, it is estimated by using an approximation of the negentropy introduced by Hyvarinen in the context of independent component analysis. PMID- 17281781 TI - Application of region selective embedded zerotree wavelet coder in CT image compression. AB - Compression is necessary in medical image preservation because of the huge data quantity. Medical images are different from the common images because of their own characteristics, for example, part of information in CT image is useless, and it's a kind of resource waste to save this part information. The region selective EZW coder was proposed with which only useful part of image was selected and compressed, and the test image provides good result. PMID- 17281782 TI - Multiscale display processing of radiographic images acquired with a protoype flat panel detector. AB - This paper study softcopy display algorithms of digital radiographic images acquired using a prototype flat panel detector. The processing is manipulated in two steps. Firstly, a look up table is applied to map the gray value of original image into proper visual scope. Then, the mapped image is decomposed into a serial subband images with a multiscale pyramid structure. The contrast of subband images are enhanced by using nolinear functions. Both performance and computational simplicity make our algorithms attractive. PMID- 17281784 TI - A design of bioimpedance spectrometer for early detection of pressure ulcer. AB - Prevention of pressure ulcer (PU) has been hampered for a long time by limitations of present risk assessment methodologies for carers. This paper introduces a novel solution of a portable bioimpedance spectrometer (BIS), which is designed to detect in vivo subtle changes in electrical properties of tissues at the portentous onset of PU and thereby establish a reliable assessment method for early detection of PU. The principle of the modified tetrapolar method applied in BIS and system designing methodology are explained thoroughly in this paper. The BIS system can measure complex impedance of human tissues over a wide range of frequencies from 10Hz to 1MHz based on direct digital synthesis (DDS) technique. Different from conventional bioimpedance measuring systems based on phase sensitive detection, the new BIS system shows its integrity in theoretical analysis and simplicity in practical implementation. As an objective, fast, straightforward, and inexpensive technique that captures fundamentally different information than subjective assessment and optical judgment, the new BIS may bring to clinical use for risk assessment of PU in the future. PMID- 17281783 TI - Monitoring system of cell's viability and function for bioartificial liver support system. AB - OBJECTIVE: To develop an online cell monitoring system for rapid understanding the cell's viability and functional activity, hence appropriate measures could be adopted in time. METHODS: Traditional off line technique was changed into online monitoring in this instrument for rapid detecting albumin and urea. Monocolor light source and integrated photoelectric sensor were adopted in this system. RESULTS: It was demonstrated in experiment that this system was designed of a novel and simple construction, which could fulfill the requirements of measuring the cell's functional activity in Bioartificial liver. CONCLUSIONS: This design is proved feasible and reliable. It provides a novel system to monitor cell's viability and function on line quickly. Using this monitoring system, the closed loop controlling of Bioartificial liver support system can be realized. PMID- 17281785 TI - New tetrapolar method for complex bioimpedance measurement: theoretical analysis and circuit realization. AB - This paper describes the theory and practical implementation of a new tetrapolar (four-electrode) method for measuring complex bioimpedance of local tissue. The new tetrapolar method adopts three independent voltages Vin+,Vin-,VR respectively from the two voltage electrodes and the sample resistor R, which is connected in serial with one of the two current electrodes. Theoretical analysis shows that the real part Zreal and imaginary part Zimag of the complex impedance between two voltage electrodes can be acquired from the modular ratios (Vin/Vr), (Vin-/Vr) and phase differences (thetaIN+-thetaR), (thetaIN-thetaR) through simple calculation. Realization of this method, based on the newest generation of highly integrated electronic components for directly generating relevant amplitude ratios and phase differences, is simple. Compared with the conventional tetrapolar method, the new tetrapolar method shows its advantage of simplicity in circuit realization, enables complete microprocessor control of localized bioimpedance measurements, and may liberate the traditional bioimpedance measuring system from the complexity of electronics. PMID- 17281786 TI - A computer-based diagnosis system for early glaucoma screening. AB - Glaucoma is a serious eye disease and the major cause of blindness worldwide. Glaucoma screening is a useful way in detecting the disease at an early stage. This paper presents a computer-based glaucoma screening system in which optic nerve defects detection, visual field examination, and expert system rules are combined to increase the sensitivity and specificity. Several fundus image processing methods are used and a histogram model is given especially for combed hair retinal nerve fiber layer defect. A visual field test performed on computer monitor is adopted to reduce the cost for other perimetry equipments. The assistant diagnostic module can give a primary diagnosis based on a set of fuzzy rules. The system is cost effective and suitable for detecting early stage glaucoma, especially for large-scale screening. PMID- 17281787 TI - Quantitative evaluation of spasticity in upper limbs in hemiplegic subject using a mathmatical model. AB - This is a proposal for a new technique for evaluating spasticity in the upper limbs of hemiplegic patients. Each subject sat on a chair or stood up, and his or her forearm was extended or flexed by a physician. The subject was instructed to relax. The elbow joint angle, torque, and electromyograms (EMGs) of the biceps brachii, triceps brachii, and brachioradialis muscles were measured. The relationship between the elbow joint angle and torque was approximated with a mathematical model, which consisted of elastic components depending on both muscle activities and elbow joint angle, by the least squares method. The inertia and visco-elastic coefficients were obtained. The elbow angle response was then estimated with the obtained inertia and visco-elastic coefficients by the Runge Kutta method, and the estimated elbow angle was compared to the observed one. The relationships between the elbow angle and torque were approximated well with the model. Next, the average elasticity was calculated and compared to the modified Ashworth scale. The average elasticity had a tendency to increase as the Ash- worth scale increased. In addition, the average elasticity varied depending on the posture of the subjects. PMID- 17281788 TI - A change of blood flow during strenuous physical exercises using cycle ergometer. AB - Our purpose of the study is to measure the blood flow in the carotid artery during physical exercises. We have developed the blood flow velocimeter during physical exercises by using the non-invasive Doppler ultrasound method. We used it and measured blood flow in the carotid artery in which using a cycle ergometer and had two exercise tests in this report. The protocol exercise with transient response and ramp response were conducted. As a result, maximum blood flow velocities changed largely during physical exercises. In particular the maximum blood flow velocity was decreased during physical exercise in transient response. In addition, we could also detect arrhythmia that occurred in the subject immediately after exercise. For this reason, blood flow measurement during physical exercise maybe useful for the early detection of cardiovascular disease. Recently, the physical exercises are very popular for health maintenance. PMID- 17281789 TI - Minimum diameter of the velocity-type respiratory air flow transducer. AB - Respiratory tubes with the length of 35 mm and the diameters of 10, 15, and 20 mm were specially made and both the static(Ps) and dynamic (Pd) pressures were simultaneously measured for steady flow rates ranging 1-12 l/sec. Least squares analysis resulted successful fitting of Ps and Pd data with quadratic equations with correlation coefficients higher than 0.99(P<0.0001). The spirometric measurement standards of the American Thoracic Society(ATS) were applied to Ps data, which demonstrated the smallest tube diameter of 15 mm to satisfy the ATS standards. The maximum Pd value of the velocity type transducer (the functional single use respiratory air flow tube) with the diameter of 15 mm was estimated to be 75 cmH2O, implying more than 7 times larger sensitivity than the widely used pneumotachometers. These results showed that the velocity type respiratory air flow transducer is a unique device accomplishing miniaturization with the sensitivity increased, thus would be of great advantage to develop portable medical devices. PMID- 17281790 TI - An improved peak quantification algorithm for automatic heart rate measurements. AB - This paper proposes a new method improving the peak quantification algorithm (PQA) introduced by Navakatikyan, et al. In measuring a human heart rate (HR). Experiments reveal that although the PQA can accurately measure the heart rates based on electrocardiogram (ECG) waveforms, this algorithm is too complex and uses too much memory, resulting in substantial reduction in accuracy when applied such algorithm to an embedded system. The proposed improved-peak quantification algorithm (improved-PQA) can rapidly analyze the heartbeat waveforms and still accurately measure the heart rates even when it is adopted in an embedded system with a lower computational power and speed. PMID- 17281791 TI - Development of the system to detect and process Electromyogram signals. AB - This paper is about the design of a system that can detect four channel electromyogram (EMG) signals. EMG signals can be acquired, transformed into electrical signals and input into computer through AD acquisition card. The computer then processes the data and the signal figures are displayed on the screen. In the signals processing system various methods integrated such as adaptive filtering, the methods in time domain, the methods for frequency analysis, and also some newly developed methods, e.g., wavelet transform. The nonlinear tools such as the recurrence quantification analysis (RQA) also has been introduced to analyze the surface EMG and has shown particularly promising for the detection of muscle statue changes. The basic construction of the system and the software analysis are introduced. PMID- 17281792 TI - Design of two-dimensional coils for wireless power transmission to in vivo robotic capsule. AB - This paper presents a design of two dimensional receiving coils to provide hundreds of milli-watt power via inductive link to in vivo robotic capsules, whose orientation are practically undetermined. The wireless power transmission system consists of a transmitter powered by class E power amplifier, and receiver with 2-dimensional antenna, rectifier, and voltage regulator. Two types of 2 dimensional antennas are designed and evaluated by theoretic and experimental analysis. Experimental results show that the proposed 2-D receiving antenna could deliver the power homogeneously against its orientation, with less than 20% of variation of the possible maximum power. PMID- 17281793 TI - Relative location estimation of power-receiver from transmitter for in vivo robotic capsules. AB - This paper presents an estimation method of the relative location of the power receiver from the transmitter for in vivo robotic capsules. The proposed method utilizes the fact that the needed current for driving the power transmitter is increased when the receiver coil is inductively coupled with the transmitter coil. By investigating the current increase characteristic according to the relative locations of the receiver, we draw an estimation strategy on the relative location of power-receiver from the transmission coil. PMID- 17281794 TI - Spatial resolution in the electrical impedance tomography for the local tissue. AB - Electrical impedance tomography (EIT) is one of the medical tissue diagnosis devices and it creates a two- or three-dimensional image of electrical impedance distribution in a living tissue. It is used for imaging the information of tissue structures, and physiological functions and states of the tissue. However, there are several problems to achieve the practical use of EIT, which are an inverse algorithm for estimating parameters and electrode structure and so on. EIT is calculated from impedance data, which is measured non-invasively by surface electrodes. Therefore, it is important to choose a proper electrode structure to realize a practical EIT measurement system. In this study, we used a electrode structure, called "divided electrode", which is proposed for a short time measurement of bio-impedance in a cross section of the local tissue. Its capability is examined by computer simulations, where a distributed equivalent circuit is used as a model for the cross section tissue. Estimation of impedance parameters is carried out by use of the Newton method. The objective of this study is to examine the spatial resolution on the circuit model. Moreover, the current flowing in the circuit model is examined. PMID- 17281795 TI - Estimation of vocal tract shape for VCV syllables for a speech training aid. AB - Display of vocal tract shape can be used in speech training aids for the hearing impaired children, as it provides a visual feedback of the articulatory efforts. Estimation of vocal tract shape, based on LPC and other analysis techniques, works satisfactorily for vowels but generally fails during stop closures. Indication of correct place of articulation is very important, particularly for non-labial consonants. In order to study the dynamics of the vocal tract shape estimation during transitions at vowel-consonant boundaries, we have used "areagram", a spectrogram-like two-dimensional (2D) display of estimated vocal tract cross-sectional area as a function of time and position along the tract length. Area estimation is based on reflection coefficients obtained from LPC analysis of speech. Based on estimated area during the transition segments preceding and following the stop closure, bivariate polynomial surfaces are obtained and these are used for estimation of the vocal tract shape during stop closure by performing 2D interpolation. The place of closure for various stop consonants could be estimated satisfactorily from the conic surface approximation. PMID- 17281796 TI - Modular measuring system for assessment of the thyroid gland functional state. AB - Distributed modular system BioLab for biophysical examinations enabling assessment of the thyroid gland functional state is presented. Two smart sensors modules measuring 4 different biosignals are connected to an Ethernet based network and enable to obtain peripheral indicators of human cardiovascular and neuromuscular functions. Personal notebook or desktop computer with a network interface controls the sensors and performs processing and evaluation of measured biosignals. PMID- 17281797 TI - A fundamental study on parameter estimation of layerd local tissue impedance for EIT. AB - Electrical Impedance Tomography (hereinafter referred to as EIT) is 2-D or 3-D image of electrical impedance distribution in a living tissue. Unlike usual imaging methods, i.e., Xray-CT, MRI and US Imagings, EIT is used for imaging the information of tissue structure and functions. This paper provides a new estimation method as a fundamental study to realize a EIT for local biological tissue. Up until now we has proposed a new configuration of the electrodes, called divided electrode, for a high-speed measurement of bio-impedance in a cross section of a local tissue. The cross section of the tissue was represented by space distributed equivalent circuits of tissue structure known, and their parameters were estimated by inverse algorithm. In this paper, we try to estimate the parameter value of a layered structural model, the thickness of the layer, and the boundary without using US-imaging by using the divided electrode. Its capability is examined by computer simulations, where a distributed equivalent circuit is used as a model of the tissue. Estimation of impedance parameter is carried out by use of the Gauss-Newton method. Usefulness of the proposed method is confirmed by computer simulations using a typical layered tissue model. PMID- 17281798 TI - New approaches to physiological study by telemetry technology. AB - Telemetry technology offers possibility to observe physiological activity of animals in a nature state. In this paper, 24h physiologic signals of rats under different conditions were recorded. New indices for blood pressure evaluation were developed. Meanwhile, approaches to heart rate variability spectrum analysis, linear and non-linear analysis of electroencephalogram (EEG) were developed to estimate the activity of autonomic nervous system and central nervous system, respectively. The results demonstrate that the new parameters extracted from telemetry data may reveal more efficient information of physiological activity, which is impossible by conventional methods. The results also provide the evidence that the activity of central nervous system relates closely to the sympathovagal balance and the sympathetic activity. PMID- 17281799 TI - A multi-channel device for respiratory sound data acquisition and transient detection. AB - In this study, a multi-channel analog data acquisition and processing device with the additional feature of detecting adventitious sounds has been designed and implemented. The overall system consists of fourteen microphones attached on the backside, an airflow measuring unit, a fifteen-channel amplifier and filter unit connected to a personal computer (PC) via a data acquisition (DAQ) card, and an interface and adventitious sound detection program prepared using LabVIEW (6.0, National Instruments) and MATLAB (7.0.1, MathWorks). The system records the fourteen-channel respiratory sound data at the posterior chest wall and in addition measures the air flow to synchronize the pulmonary signal on the respiration cycle. Respiratory data are amplified and band-pass filtered, whereas flow signal is only low-pass filtered since it is a low-frequency signal with sufficiently high amplitude. All data are sent to a PC to be digitized by DAQ card, then to be processed and stored. An algorithm based on wavelet decomposition is developed which detects the adventitious pulmonary sounds, mainly the crackles and wheezes. This system is intended to be used for mapping the pulmonary sounds and detecting and locating the adventitious pulmonary sounds. PMID- 17281800 TI - Monitoring diabetic wound healing by NIR spectroscopy. AB - Chronic wounds represent one of the most serious complications of diabetes. Lack of quantitative assessment of healing progress makes diabetic wound management a clinical challenge. We constructed an optical device based on near infrared diffuse optical spectroscopy and monitored the change in wound optical properties during healing. A single source, four detector frequency domain instrument with multiple wavelengths was employed in a streptozotocin induced diabetic rat animal model. Optical properties including absorption and reduced scattering coefficients were measured. Our results show that there is significant difference in the absorption and reduced scattering coefficient of the wounds between diabetic and controls rats, and such difference persists throughout the healing period. Our technique would be highly useful in monitoring and quantifying the wound healing process. PMID- 17281801 TI - Spatial-temporal analysis of uterine smooth muscle activity recorded during pregnancy. AB - We performed recording of the magnetic fields (Magnetomyography - MMG) corresponding to the electrical activity of the uterine smooth muscle with a device called SARA, (SQuid Array for Reproductive Assessment). Past studies suggest that the uterus passes through a preparatory process before entering labor and resulting in delivery of the fetus. But the electrophysiological mechanism of this process is not completely understood. We propose four parameters that will allow us quantify the characteristics of the uterine MMG signal obtained from 151 sensors spread over the pregnant abdomen. In summary, we believe that spatial-temporal analysis mapping of uterine activity will help us better understand the process of labor. PMID- 17281802 TI - Heartbeat detection using energy thresholding and template match. AB - Heartbeat detection is very important for retrieving the vital signs of heart functions. The morphologies and inter-beat intervals of heartbeats can reveal the condition of heart contraction. In this paper, we developed a heartbeat information integration scheme to deal with the information yielded by the energy thresholding and template match methods, which are usually used to detect the heartbeats and match the QRS, respectively. The proposed method are developed in SIMULINK 2.0 and assessed by the MIT/BIH arrhythmia database. The result demonstrated excellent sensitivity of detecting QRS and ventricular premature contraction in the proposed method. PMID- 17281803 TI - Analog signal processing for heart rate extraction. AB - Heart rate variability (HRV) studies have shown that beat-to-beat interval variability is a strong indicator of a number of medical conditions, including heart failure, diabetes, and hypertension. Current HRV systems typically analyze pre-recorded high resolution ECG recordings. We have demonstrated an analog signal processing circuit which extracts real-time HRV data from EGC signals producing a simple output voltage that is more easily monitored or recorded. The system is accurate and can be produced as a compact low-cost device that can make HRV monitoring more practical for home based health care and implantable devices. PMID- 17281804 TI - Instrumentation for fetal cardiac performance analysis during the antepartum period. AB - Cardiotocography as a simultaneous recording of fetal heart rate (FHR) and uterine contraction activity is a basic method for evaluation of fetal condition. Continuous variability of the fetal heart rate is an indirect sign of adequate oxygenation of a fetus. Unfortunately, the reverse case is not always true, signs suggesting pathological changes can also appear in recording when the fetal is not at risk. The cardiotocography shall then be recognized as a more screening than diagnostic method. It will be interesting to develop a noninvasive method being complementary to routine cardiotocography. This method should allow the adequate prediction of a bad clinical outcome when the test is abnormal. The paper presents the system that makes possible cardiotocograms analysis in parallel with the assessment of additional parameters determined from comparison of mechanical and electrical fetal heart activity signals. The studies are aimed at development of set of parameters that are high correlated with fetal outcome. PMID- 17281805 TI - Study on the error in the dynamic spectrum method relative with the pathlength factor as a function of wavelength. AB - Utilizing near-infrared spectroscopy for non-invasive blood component concentration sensing has been a focusing topic in biomedical optics applications. The ease of use, low cost and portability of these methods is a clear advantage over the invasive blood component concentration sensing which is the main sensing method in the clinic application. However, there is no report about any successful non-invasive blood components (except the artery blood oxygen saturation) concentration detection techniques that can meet the requirements of clinic application. One of the most key difficulties is the influence of the individual discrepancy. Dynamic spectrum (DS) is a new measure method of non-invasive blood components concentration sensing presented recently. It can eliminate the individual discrepancy of the tissues except the pulsatile component of the artery blood (PCAB) theoretically. This indicates a brand new way to measure the blood components concentration and a potential to provide absolute quantitation of hemodynamic variables. One of the systematic errors in the calculation of the component changes from NIRS data of the dynamic spectrum is the absolute magnitudes and relative differences in pathlength factors as a function of wavelength. Monte Carlo simulations are used in this paper to examine the importance and mitigation methods of this error while the photoelectric pulse wave is detected on the finger tip. We found wavelength selection to be important variables in minimizing such errors, and replacing the average pathlength factor with the subsection pathlength factor appropriately could reduce the error to a small fraction (10%). PMID- 17281806 TI - A provocative test to determine brain compliance in the management of patients with hydrocephalus. AB - Non-invasive techniques to explore intracranial compliance and pressure have been extensively explored in recent years. Previous techniques have used expensive technologies to make these measurements, often with difficulty. We present a novel, inexpensive method and algorithm to observe trends in intracranial compliance measurement targeted towards the treatment and management of hydrocephalus. The technique uses two photo-plethysmographic sensors to record arterial pulse perfusion, a common tilt table apparatus to methodically and artificially increase intracranial pressure, and a digital signal processing algorithm to determine phase difference between the waveforms. A secondary phase difference disease signature approach is also hypothesized. PMID- 17281807 TI - Preliminary investigation of breast tumor detection using cross-vivaldi antenna. AB - The contrast in dielectric properties between normal breast tissues and malignant tumors is significant. Based on this fact, detection of breast cancer with microwaves has been proposed. Here, a cross-Vivaldi antenna capable of measuring cross-polarization is investigated for tumor detection. Observation of cross polarized reflections reduces reflections from surfaces such as skin, permitting more reliable detection of small tumors. Simulation results indicate that the antenna has the potential to detect breast tumors using this approach. PMID- 17281808 TI - Modeling of a gas concentration measurement system. AB - Energy expenditure can be calculated via measurement of oxygen consumption and carbon dioxide production. Precise measurement of expired gas concentrations and volume is required for this determination. For a given gas concentration measurement system, the establishment of a model is a good way to effectively use the equipments and achieve more accurate energy expenditure calculations. This paper proposes a simple but effective approach for the modeling of a gas concentration measurement system. PMID- 17281809 TI - Construction of devices in bioartificial liver support system. AB - An automatic control device in Bioartificial Liver Support System is designed and implemented. Details of the hardware structure, design of the control system and the applied software in the device are described. Main controller uses the WS 843AW industrial control computer; precision electromagnetic valves are selected as implements to control the flux of three-gases (oxygen, carbon dioxide and nitrogen). The interconnected rule of controlled parameters in the system is analysed, and then matched by the mass balance equation. By a series of logic judgements of signals from sensors and direct digital calculations (DDC), a simple proportional plus integral (PI) controller can firstly manipulate the operations of electromagnetic valves, and then the on-line and off-line predictive control algorithm is used in accordance with practical experience to meet the requirements of the parameters in the culture and metabolism of hepatocytes. Software based on Visual C++ is implemented. All these serve to ensure high operational reliability, expansibility and better maneuverability of the whole system. Experiments show that this method can achieve sound performances in practice although there exist very strong coupling, dead-delay and lots of non-linear factors in the bioreactor. The controlling range is: Dissolved Oxygen 0-200±5%; pH 6-8±0.05pH; Temperature 20 45±0.1°C. CONCLUSION: The device can work in a steady state, and the control precision is high. It can meet the needs in the Bioartificial Liver Support System, and hopefully improve clinical therapeutic effect. PMID- 17281810 TI - Minimizing Excessive Stimulus during Electric Pulp Testing. AB - Electric pulp test is a method to examine the vitality of dental pulp using the electrical stimulation. During the pulp test, the current stimulates intradental nerve, and give severe pain to patients. Some studies were accomplished to measure the responses of subjects by stimulating over the sensory threshold. But these studies were focused on the time delay of subject's response after stimulating over the threshold. The purpose of this study was first to measure the excessive stimulation time during pulp testing by means of EMG in anterior belly of digastric muscle, voice, and finger movement, secondly, to determine whether the excessive stimulation time could be reduced by the specially designed automatic circuit breaker on the basis of EMG signal. PMID- 17281811 TI - Assessing the Effectiveness of Increased FIO2for Enhancing Driver's Activation State Using Simulated Monotonous Driving. AB - Lowering of what we term a driver's Activation State (AS) during monotonous driving conditions may increase the risk of an accident. To develop an in-car environment that allows active driving - "Biofee dforward System" - we have investigated the effects of applying a stimulus of increased inspired oxygen fraction (FIO2) supply on a driver's AS, using simulated monotonous driving. We used our previously substantiated index of As derived from beat-by-beat blood pressure (BP) response following an electrical stimulus. We have made physiological measurements including BP and found that the increased FIO2stimulus is effective in enhancing the AS. This finding was also confirmed in terms of the autonomic activity balance as well as the lengthening in time for active, safer, driving. PMID- 17281812 TI - Changes in electrical and physiological properties of human blood during storage. AB - In this study, the relationship between physiological parameters and electrical impedance changes of human blood and their further clinical implications are investigated. The study is performed on 255 erythrocyte suspension samples derived from 51 male donors. The samples are stored at 4°C and measurements are done on the 0th, 10th, 21st, 35thand 42nddays of storage. The complex impedance is measured in the frequency range from 100 kHz to 1 MHz. The extracellular resistance Reand the effective cell memebrane capacitance Cmincreased progressively with storage time while the intracellular resistance Rihas decreased. Electrical impedance alterations are explained in terms of the measurements of Na+, K+and Cl-concentrations, pH and ATP. Storage of red blood cells resulted in a rise in the extracellular K+and a fall in the extracellular Na+, Cl-, pH and ATP. Variance analysis (ANOVA) is used to evaluate any variations in blood parameters, in relation to storage time. According to the (SPSS) regression analysis, Riand Reare highly correlated with Na+, K+, Cl-and pH and, more significantly with ATP. The Cole-Cole parameters Fcand α showed very little change with storage time and Cmhad weak correlations with blood parameters. Results show that complex impedance measurements may serve as a useful indicator in the quality assessment of blood bank stored blood samples. PMID- 17281813 TI - Autoregressive spectrum of transient evoked otoacoustic emissions: methods and applications. AB - The transient evoked otoacoustic emissions (TEOAEs), elicited by a transient sound, is similar to the impulse (or white noise for a random process) response of a system. It fully reveals the information of cochlea in frequency domain. The aim of present study is to apply the autoregressive (AR) spectrum analysis to TEOAEs signal in our OAEs detection system and to find a new quantitative index of cochlear status. The AR spectrum is also applied to TEOAEs with contralateral acoustic stimulation (CAS) to study the function of medial olivocochlear system. The results show clearly that the AR spectrum of TEOAEs signal can be a promising method for diagnosing the impairment of cochlea and medial olivocochlear system. PMID- 17281814 TI - Local activity levels guided adaptive scan conversion algorithm. AB - Digital scan converter in ultrasound machine prepares data in display buffer for displaying ultrasonic echo signals on monitor with interpolating missed pixel values. The popular bilinear interpolation and bicubic interpolation in scan conversion blurred image edges and detail regions. An adaptive scan conversion algorithm was proposed with applying warped distance interpolation to enhance image edges. And local activity level threshold distinguished smooth regions from detail regions to preserve sharpness in smooth regions. Simulation result indicated that result ultrasound images were superior to other common algorithms. PMID- 17281815 TI - On gravity correction for training and rehabilitation lower limbs machine. AB - During a training or rehabilitation session on an isokinetic machine for lower limbs also known as dynamometer, it's necessary to know the real muscular effort by compensating the gravity or undesirable dynamic effects. Thus, the aim of this work is to give a theoretical study and experimentally evaluation of two gravity correction methods. We'll then discuss the advantages and drawbacks of each method and give new trends to follow in this domain. PMID- 17281816 TI - Phototherapy of the newborn: a predictive model for the outcome. AB - Jaundice in one of the most common problems of the newborn. In most cases, jaundice is considered a physiological transient situation, but sometimes it can lead to death or serious injuries for the survivors. For decades, phototherapy has been used as the main method for prevention and treatment of hyperbilirubinaemia of the newborn. This work aims at finding a predictive model for the decrement of blood bilirubin followed conventional phototherapy. Data from 90 patients were collected and used in the multiple regression method. A rigorous statistical analysis was done in order to guarantee a correct and valid model. The obtained model was able to explain 78% of the variation of the dependent variable We found that it is possible to predict the total sugar bilirubin of the patient under phototherapy by knowing its birth weight, bilirubin level at the beginning of treatment, duration of exposition, and irradiance. Besides, it is possible to infer the time necessary for a given decrement of bilirubin, under approximately constant irradiance. PMID- 17281817 TI - Designing a Signal Conditioning System with Software Calibration for Resistor feedback Patch Clamp Amplifier. AB - In this paper, a programmable signal conditioning system based on software calibration for resistor-feedback patch clamp amplifier (PCA) has been described, this system is mainly composed of frequency correction, programmable gain and filter whose parameters are configured by software automatically to minimize the errors, A lab-designed data acquisition system (DAQ) is used to implement data collections and communications with PC. The laboratory test results show good agreement with design specifications. PMID- 17281818 TI - A diagnosis system for the spinal column nerve damaged patients. AB - Visible evidence of spinal column damage is only apparent in 14% of the patients who receive spinal damage. We use a humidity sensor array. The humidity sensor (HDP-05) is arranged and attached to pre-assigned regions along the spinal column nerve of the actual patient. Applying pressure to the urinary bladder causes the patient to sweat. It is possible to determine which spinal column autonomic nerve is damaged in a region by humidity value. But also have some problem is that sometimes the damaged region has same value as a normal region. If will find a better attachment method and a more sensitive sensor could be found the results will be better and more precise. PMID- 17281819 TI - Development of the Portable Blood Glucose Meter for Self-monitoring of Blood Glucose. AB - The work outlined in this paper is towards developing a portable, economy blood glucose meter for self-monitoring of blood glucose, which has high performance price ratio with multifunction and is attractive to the average people. Its functions include blood glucose concentration measurement, LCD display, historical records restore, calendar/timer. It enables the patients with diabetes to detect blood glucose with a glucose oxidase electrode independently at home. This paper will outline hardware configuration in the implementation and software management. Especially, graphic trend curve on LCD allows individuals to easily see how actual blood glucose readings compare with historical records stored in the meter and show how individuals stay within their specific target range so that they can determine how well they are controlling their diabetes. Experimental results indicate that this device is easy-to-use and suitable for home blood glucose monitoring for patients. PMID- 17281820 TI - PhysioTrace: An efficient toolkit for biomedical signal processing. AB - Healthcare monitoring applications requires the measurement and the analysis of multiple physiological data. In the field of biomedical research, these data are issued from different devices involving data centralization and synchronization difficulties. On the other hand, the analysis of the acquired data requires high level digital signal processing tools. In this paper we describe a real time toolkit for biomedical data acquisition, centralization, processing and visualization. This toolkit, composed of both hardware and software modules, allows users to model, test and perform all kind of digital signal processing algorithms for all kind of biomedical signals. These highly efficient hardware and software modules have been developed and tested especially for biomedical studies and used in a large number of clinical investigations. So, for developers, using such a toolkit will reduce the development time while increasing the application performances. PMID- 17281821 TI - Time-frequency analysis of endogenous calf skeletal muscle vibromyograms. AB - Calf skeletal muscle pump activity is essential for maintaining adequate venous and interstitial fluid flows in the dependent body. Correspondingly, failure of this extracorporeal pump leads to a host of acute and chronic physiological complications. The focus of this study is to assess the calf muscle pump contractility, more specifically through analysis of soleus muscle firing dynamics, in supine and seated positions, utilizing vibromyography (VMG). We have extended our previous investigations which relied on Fourier analysis of VMG recordings by utilizing wavelet-based time-frequency analysis to characterize the intrinsically non-stationary peripheral postural muscle dynamics during quiet sitting. Our objective was to identify the fibers types responsible for muscle pump activity during sitting, by looking for significant increases in activity in specific muscle fiber groups when a subject assumes an upright position from recumbency, and examine their temporal dynamics. PMID- 17281822 TI - FOR SAFE: instrumented and secured obstetrical forceps. AB - Operative vaginal deliveries represent a significant amount of vaginal deliveries. Operative delivery involves either forceps either vacuum extraction. Complications are frequent but rarely severe (cutaneaous lesions, facial palsy...). However, it is essential to limit these complications by helping the obstetrician to position his extraction instrument. It is the aim of the FOR SAFE device: provide a new instrumented forceps which performs the interface pressure measurement between the fetal head and the shanks of the forceps. Interface pressure evaluation requires interaction between the living tissue and the sensor, just like a man needs to touch an object with its fingertip to evaluate its compliance. The design of the sensor is "bio inspired". The sensor interacts with the matter, without modifying phenomenon to be measured. PMID- 17281823 TI - Electromagnetic tracking for image-guided abdominal procedures: overall system and technical issues. AB - This paper summarizes our work over the past several years in developing an image guided system based on electromagnetic tracking for abdominal interventions. The paper begins with a review of computer-aided surgery and electromagnetic tracking. We next describe our image-guided system along with phantom and animal studies. We then present some technical issues in improving accuracy including pivot calibration, dynamic referencing, and registration using two 5 degree-of- freedom sensors. Electromagnetic tracking has great potential for assisting physicians in precision placement of instruments during minimally invasive interventions. However, the accuracy of these systems needs to be validated in the clinical environment and issues such as respiratory motion and organ deformation need to be addressed. PMID- 17281824 TI - Computer aided tongue diagnosis system. AB - To circumvent the subjective and qualitative problems of traditional tongue diagnosis, we present a novel computer aided tongue diagnosis system (CATDS). In this system, a standard acquisition device as well as a new color correction method is utilized to capture qualified tongue images. The system is constituted by five components: User Interface Module, Acquisition Module, Tongue Image Database, Image Preprocessing Module and Diagnosis Engine. In contrast to existing CATDS, the proposed system aims to establish the relationship between quantitative features and diseases via the Bayesian networks. System tests are carried out on a group of 544 patients affected by 9 common diseases and 56 healthy volunteers. The results show that the system can properly identify six groups: healthy, pulmonary heart disease, appendicitis, gastritis, pancreatitis and bronchitis with accuracy higher than 75%. Moreover, the execution time for the whole diagnosis process including image preprocessing and diagnosis is less than 5 seconds. PMID- 17281825 TI - A Novel Design of a Portable Otoacoustic Emissions Detecting System Based on ARM. AB - Most traditional designs of otoacoustic emissions (OAEs) detecting system adopt the model of "sensor + sound signal sampler / generator + personal computer". This kind of model has shortcomings that it is apt to introduce exterior noises and lacks system integration, which often brings much inconvenience into the process of measuring. There are also some other OAEs detecting systems that use a digital signal processor (DSP) to collect and process the OAEs response signals, but a DSP is not a best choice to perform as a control unit on a portable device for that they usually do not have many peripheral hardware interfaces and are relatively demanding in cost. Different from the fore-mentioned two kinds of control unit, ARM is a kind of elegant new design, with a complete set of common system peripherals, to provide hand-held devices with low-cost and high performance microcontroller solution in small die size. In this article, a novel design of a highly integrated and network-accessed portable otoacoustic emissions detecting system based on ARM (mainly for TEOAE and DPOAE) is presented. In addition, a comparison of the differences in the system's real-time performance based on different microcontroller units is provided to justify the use of ARM. PMID- 17281826 TI - The Design of Glioma Hyperthermia Instrument Based on Fuzzy-PID. AB - Fuzzy-PID control is introduced to glioma Hyperthermia, the system structure chart of Hyperthermia is given, Fuzzy-PID arithmetic, control rules and the time response figure are illuminated in detail. The simulation figure of the heating field characteristic and circuit of temperature measure are given. Finally, the clinical result of this instrument is introduced, which is in animal experiment. PMID- 17281827 TI - Advances in hyperthermia technology. AB - Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures. Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues. In the clinical application of hyperthermia, three methods can be distinguished: local, regional and whole-body hyperthermia. Hyperthermia is under study in clinical trials and is not widely available. So further technological improvements will need to contribute to an easier and better controlled adequate application of hyperthermia. PMID- 17281828 TI - Heating characteristics of a RF hyperthermia for deep-seated regions. AB - Electromagnetic and heat-transfer equations were solved to investigate a radio frequency (RF) rectangular resonant cavity applicator. The possibility of heating a deep-seated tumor was demonstrated. A torso-shaped dielectric phantom was made. It has electrical constants resembling those of human muscle. Several L-type antennas were made and placed at appropriate locations to heat a deep region. Measured results agreed with the calculated results. Results show that the rectangular resonant cavity applicator with the L-type antennas can heat deep seated tumors. PMID- 17281829 TI - Improvement of the resonant cavity applicator for brain tumor hyperthermia - Experimental heating results -. AB - A re-entrant type resonant cavity applicator for deep tumor hyperthermia treatment was presented. In this method, a human body is placed between the gap of the inner re-entrant cylinders, and is heated with electromagnetic fields stimulated in the cavity without contact between the surface of the human body and the applicator. In this paper, two methods to control the heating pattern were proposed. In the first method, a human body was moved towards the electrode. In the second method, the diametric ratio of the inner electrode was changed. The controllable range of heating pattern was about 20% of the distance from the center of the agar phantom in the direction of depth. PMID- 17281830 TI - Experimental study on ultrasonic thermal chemotherapy for tumor treatment. AB - Ultrasound Thermal Chemotherapy (UTC) method was used to investigate the mechanism of apoptosis of tumor cells induced by ultrasound thermal therapy combined with thermosensitive drug in Mice Tumor Model (MTM). And the optimal parameters of ultrasonic, such as frequency, dose, sound field, treatment time and temperature, were found by the animal trials which the Tca8113 cells had been inoculated into the body of nude mice. Experimental results showed that the optimized thermal treatment technology of ultrasonic combined with the chemotherapy could produce obvious inhibitory effects of the tumor's growth. We also found that apoptosis reached its highest levels in the 6thto 10thhour, then gradually decreased and nearly resumed the normal level after the 12thhour. UTC method could induce tumor cells to die significantly. PMID- 17281831 TI - Experimental study on fracture mechanics properties of frozen rabbit aorta. AB - To more scientifically discuss fracture problems associated with cryopreservation of aorta, the effects of temperature, cooling rate and cryo-protective agent on the fracture mechanics properties of frozen rabbit aorta have been investigated with Dynamical Mechanics Analyser (DMA), and the test method for crack criterion of frozen rabbit aorta was also explored. The results show that: As temperature decreasing, the fracture modes of frozen rabbit aorta are from typical ductile fracture to typical brittle fracture, and its resist-fracture ability weakens remarkably from -20 centigrade to -80 centigrade. The cooling rates have no effects on the fracture modes when cooled to -50 centigrade, but the resist fracture ability of frozen rabbit aorta will be stronger when the sample treated by a higher cooling rate. Due to the hydration action of dimethyl sulphoxide (DMSO), the rabbit aorta permeated by 10% (V/V) DMSO presents typical ductile fracture when it was cooled to -50 centigrade, so its resist-fracture ability is enhanced obviously. Compared to the axial sample, the peripheral sample's resist fracture ability is larger than that of the former. PMID- 17281832 TI - Study of the Vascular Endothelial Cell Shape Change during Freezing. AB - Microvascular injury is recognized as a major tissue damage mechanism of ablative cryosurgery. Details of this injury mechanism are not completely understood. ECMatrix™ 625 was used to mimic the tumor environment and to allow the endothelial cells cultured in vitro to form the tube-like structure of the vasculature. Influences of water dehydration and chilling effects on the endothelial cell and the integrity of the structure during freezing were studied. It was found that the initial cell shape change was mainly controlled by water dehydration, which is dependent on the cooling rate. As the cooling prolonged and temperature lowered, further cell shape change could be induced by chilling effects on intracellular proteins, and focal adhesions to the basement membrane, resulting in the final cell rounding and detachment of endothelial cells in vivo. PMID- 17281833 TI - Capacity of brain cooling via ventilating oxygen at low temperature over respiratory tract. AB - Cerebral hypothermia is a rather useful way to improve outcome after brain injury. In this paper, the capacity of cooling oxygen ventilation (COV) during cerebral circulation arrest was theoretically evaluated. A transient two dimensional mathematical model for the heat and water vapor transport through the respiratory tract of human body was established to predict the temperature response of the brain tissue. Calculation results indicate that COV will help in some extent to reduce the inner temperature of patient brain subject to cerebral circulation arrest. However, its capacity on lowering the deep brain temperature is very limited. Therefore more powerful cooling strategies should be investigated to realize an efficient cooling on the target cerebral tissue. PMID- 17281834 TI - Tumor microvasculature response to alternated cold and heat treatment. AB - Vascular injury is an important damage mechanism of cancer treatment modalities such as cryotherapy and hyperthermia. In this study, tumor microvasculature response to locally alternated cold and heat treatment has been studied via microscope observation and histopathological analysis. The tumor vascular permeability to Rhodamine labeled 100nm liposomes at different temperatures was quantitatively studied. Murine mammary carcinoma 4T1 was implanted in the nude mice dorsal skin fold window chamber. Either cold or heat, or the alternated cold and heat treatment was imposed to the mouse tumor inside the window by a thermal chamber. There appeared massive hemorrhage in both the periphery and center of the tumor after the alternated cold and heat treatment. Histopathological analysis indicates severe vessel damage and large necrotic tumor tissue areas. Results of permeability measurements show that the liposome nanoparticles hardly extravasate into the tumor interstitium under normal conditions. But the permeability of the tumor vasculature could be significantly enhanced either by increasing or lowering the local temperature. PMID- 17281835 TI - Temperature distributions of developed needle type applicator. AB - This paper discusses radio frequency (RF) interstitial hyperthermia for a brain tumor with needle type applicators. In this method, it is necessary to make appropriate thermal distribution to the region of the brain tumor. However, it is difficult to predict the thermal distribution. We estimated temperature distribution inside an agar phantom by the finite element method (FEM), and heated agar phantom by the developed system. First, we compared computer simulation results and experimental results. Next, we discussed the heating properties of changing the inserted direction of a single type needle applicator. Finally, the temperature distribution of agar phantom heated by a multi type needle applicator was presented. PMID- 17281836 TI - Shock wave therapeutic developments. AB - Works performed in Central Clinical Air Force Hospital on shock wave therapeutic developments are presented. Results of simulation and experiments with three beams generator are presented in this report. Principal details of multi-beam shock wave generator are discussed. PMID- 17281837 TI - The Effects of Q-Switched Nd:YAG Laser Irradiation in the Wavelength of 1064nm and 532nm on Guinea Pigs' Skin Tissue. AB - To investigate the effect of Q-switched Nd: YAG laser irradiation in the wavelength of 1064nm and 532nm on Guinea Pigs' skin tissue, according to the method and dose which are used clinically to treat pigmentary skin diseases, so as to provide some reference and foundation for the clinical usage of Q-switched Nd: YAG laser. METHODS: three different doses of Q-switched Nd:YAG laser in the wavelength of 1064nm and 532nm were used repectively for in vitro irradiation on Guinea Pigs, then the histological change of the skin tissue were observed and analyzed with microscope and image analysis instrument. RESULTS: Each experimental group showed obvious histological changes, and with the increase in doses, the extent of change became larger. CONCLUSION: The single-pulse energy density of Q-switched Nd:YAG laser plays a main role in the change of the skin tissue; with the same irradiation dose there is no difference in the effects of the two wavelengths (1064nm and 532nm) on skin tissue; the green light with the wavelength of 532nm can be absorbed by epidermal melanin granules and shatter the melanin granules much more effectively than the infrared light with the wavelength of 1064nm; and in the same wavelength, the larger the dose, the better the shattering effect on melanin. PMID- 17281838 TI - Implementation of a transcutaneous charger for fully implantable middle ear hearing device. AB - A transcutaneous charger for the fully implantable middle ear hearing device (F IMEHD), which can monitor the charging level of battery, has been designed and implemented. In order to recharge the battery of F-IMEHD, the electromagnetic coupling between primary coil at outer body and secondary coil at inner body has been used. Considering the implant condition of the F-IMEHD, the primary coil and the secondary coil have been designed. Using the resonance of LC tank circuit at each coil, transmission efficiency was increased. Since the primary and the secondary coil are magnetically coupled, the current variation of the primary coil is related with the impedance of internal resonant circuit. Using the principle mentioned above, the implanted module could transmit outward the information about charging state of battery or coupling between two coils by the changing internal impedance. As in the demonstrated results of experiment, the implemented charger has supplied the sufficient operating voltage for the implanted battery within about 10 mm distance. And also, it has been confirmed that the implanted module can transmit information outward by control of internal impedance. PMID- 17281839 TI - Utilization of an alternative Communication Device using the Anal Sphincter (CDAS). AB - The purpose of this study was to invent a new communication system for terminal amyotrophic lateral sclerosis (ALS) patients who are in a state of complete motor paralysis with intact sensory and cognitive functions whose speech are disrupted due to the weakness of muscles involved in speaking and/ or to tracheostomy and ventilator dependence. PMID- 17281840 TI - Walking Using Touch: Design and Preliminary Prototype of a Non-Invasive ETA for the Visually Impaired. AB - This paper presents the design and preliminary prototype of the Intelligent Glasses, a novel non-invasive electronic travel aid (ETA) designed to assist the blind/visually impaired to navigate easily, safely and quickly among obstacles in indoor/outdoor 3D environments. The Intelligent Glasses, a joint project between the Robotics Laboratory of Paris (LRP) and the French Atomic Energy Commission (CEA), is based on a visuo-tactile system. Two mini-cameras mounted on the user's eyeglasses frame detect the obstacles ahead the walking course and translate this information to a tactile display as a map representing where the obstacles are located in the scene. The user freely explores the tactile map and is able to follow it easily, demonstrating initial feasibility of the system. PMID- 17281841 TI - Application of wearable inertial sensors in stroke rehabilitation. AB - We introduce a human arm movement tracking system that has been developed to aid the rehabilitation of stroke patients. A wearable 3-axis inertial sensor is used to capture arm movements in 3-D space and in real time. The tracking algorithm is based on a kinematical model that considers the upper and lower forearm. To improve accuracy and consistency, a weighted least square filtering strategy is adopted. The calculated motion trajectory was compared with that measured using a commerically available Qualysis tracking system. For 3D cyclical rotation, the mean wrist position error was 2.45 cm without filtering and 1.79 cm after the filtering alogorithm was applied. The experimental results demonstrate the favorable performance of the proposed framework in estimation of upper limb motion in stroke rehabilitation. PMID- 17281842 TI - Development of an EOG (Electro-Oculography) Based Human-Computer Interface. AB - We designed an inexpensive user computer interface for helping the disabled persons to communicate with their caretakers, which is based on EOG (electro oculography) signals rather than the very expensive reflectance based methods. EOG signals of different eye movement patterns are analyzed with the LOS guiding setting constructed ourselves. An effective eye movement pattern is found to control the computer. Testing conducted on 12 subjects show that this system is remarkably accurate, easy to operate and reliable. PMID- 17281843 TI - Design and fabrication of a new electrolarynx and voice amplifier for laryngectomees. AB - A Laryngectomee is a person whose vocal cords i.e. voice box is surgically removed owing to cancer or due to automobile accidents, burns or trauma. The patient, therefore permanently loses the ability to speak normally. An Electrolarynx is an electronic speech aid that enables the Laryngectomee to communicate with other people as quickly as possible after the successful removal of the larynx. A neck type Electrolarynx has been designed. Earlier designs could not alter frequency and intensity simultaneously during conversation. The Electrolarynx developed can control both frequency and intensity simultaneously during conversation. The device has been tested on the patient and found to be very effective. A portable, pocket size, battery powered voice amplifier (PA system) has also been developed which uses an electret condenser microphone as the input. The voice amplifier developed is a two stage amplifier which uses a preamplifier stage and a power amplifier stage. The output of the power amplifier is connected to a speaker. The device is being used by the patient and found to be very useful. PMID- 17281844 TI - Detection of spatio-temporal gait parameters by using wearable motion sensors. AB - This paper presents a method to detect the spatio-temporal parameters of gait by using wearable motion sensors with a gyro, accelerometer, and magnetic sensor. The detected gait parameters are as follows: stance (ST), double support (DS), and gait cycle (GC) time as temporal parameters, and the stride length (SL) as spatial parameter. Four motion sensors are attached on both thighs and shanks of users, and the sensor data are collected in a portable PC. The temporal parameters are estimated by finding walking events, and then the stride length is calculated with two gait models. The estimated parameters are compared to those obtained from a motion capture system (VICON system). PMID- 17281845 TI - A novel rehabilitation system for upper limbs. AB - Rehabilitation system for upper limbs is the device of implementing rehabilitation for patients' wounded limbs instead of therapists. According to review the development of rehabilitation system, we find some deficiencies such as insufficient movement space, few exact evaluations for impairment, and inadequate support for serious hemiplegia. Aiming at these problems, a novel rehabilitation system for upper limbs based on sEMG (surface electromyographic) signal is developed. The proposed system imitates human arm movements and can implement space motion because of its 5 DOF. As a diagnostic tool, the system is introduced sEMG, which is considered as the main basis of evaluation for motor function impairment. Software is developed to analyze sEMG signal during the movements to obtain valid characteristic parameters with time-, frequency-, and time-frequency-domain analytical methods. These parameters are associated with those of other sensor signals such as joint torque, joint angle, and force to quantify motor function injury. As a therapeutic tool, it can provide effective plans based on the parameters mentioned above. During the course of exercises, changes of each sensor signal and their characteristic parameters can be detected and monitored on the intuitive software interface, which can guide the device to carry out trainings. It provides a good platform for researching of sEMG signal and provides a new path for clinic hemiplegia upper limb therapy. PMID- 17281846 TI - RUPERT: a Device for Robotic Upper Extremity Repetitive Therapy. AB - We report the development and initial evaluation of a device for robotic assisted upper extremity repetitive therapy (RUPERT). Intense repetitive physical therapies provided by individualized interaction between the patient and a rehabilitation specialist to overcome upper extremity impairment after stroke are beneficial, however, they are expensive and difficult to evaluate quantitatively and objectively. The need is urgent and growing for a low cost, safe and easy to use robotic device to assist the patient and the therapist to fully achieve the potential benefit of task-based repetitive physical therapies. We designed a pneumatic muscle (PM) driven therapeutic device, the RUPERT, that is wearable and provides assistive forces required to move the arm during performance of several critical tasks of daily living. The robot has four degrees of freedom at shoulder, elbow and wrist. The sensors feedback position and force information for quantitative evaluation of task performance. It has the potential of providing a take-home method of supplementing therapy. The device can also provide real-time, objective assessment of functional improvement of therapy. PMID- 17281847 TI - Development of intelligential apparatus of rehabilitation for disablement of limb. AB - In this paper Intelligentized multi-functional limb treatment and rehabilitation based on computer-controlled system, is introduced. This system mainly used for treatment and rehabilitation in the disablement of limb. The range speed and training time can be automatically controlled. Training parameter and result can be monitored on computer. The apparatus has the advantages of high reliability, easy operation and compact design. It is a new kind of intelligent limb rehabilitation. PMID- 17281848 TI - Affine-representation- based Calibrationfree Augmented Reality Using Image-based Rendering. AB - Affine-representation-based calibrationfree augmented reality avoids the complicated measurements and calibration of the camera and renders virtual objects without any metric information, thus provides better usability over traditional augmented reality systems. However, the lack of metric information makes lighting computation impossible. In this paper, a novel image-based approach is proposed to simulate the lighting effect on the virtual object. The approach requires a preprocess phase in which the source images are made, and in rendering phase, the source images are selected according to the camera viewing direction. This approach provides virtual objects rendered under affine-based calibration-free augmented reality systems with a 3-D look and feel, and thus will improve the quality of the video output and the user experience under such systems. PMID- 17281849 TI - Integration of augmented reality and assistive devices for post-stroke hand opening rehabilitation. AB - Impairment of hand function is prevalent among stroke survivors, motivating the search for effective rehabilitation therapy. Recent studies have suggested that for upper extremity functional recovery, repetitive training with virtual reality is helpful. Repetitive training can be facilitated with assistance from mechanical devices. Thus, we have developed a training environment that integrates augmented reality (AR) with assistive devices for post-stroke hand rehabilitation. The AR element of our environment utilizes head mounted display and virtual objects for reach-and-grasp task training. The assistive device consists of either a body-powered orthosis (BPO) or a pneumatic-powered device (PPD), both of which are incorporated into gloves. This environment can be easily set up and calibrated, is customizable for individual users, and requires active user participation. Additionally, it can be used with both real and virtual objects, as desired. We are currently conducting pilot case studies to assess ease of use and efficacy. At present, one stroke survivor from each of the three training conditions, AR-with-BPO, AR-with-PPD and AR-only (acting as the control), has completed the 6-week training paradigm. Preliminary findings suggest user acceptance of the technology and some potential for beneficial effects. PMID- 17281851 TI - Methodics of IR Imaging in SCI Individuals Rehabilitation. AB - Temperature is one of the parameters which gives information about some physiological changes in the human body, especially in spinal cord injured (SCI) individuals and their rehabilitation. Exercise induces muscle contraction, and in interactivity with cardiovascular and respiratory system produces heat, which dilates by conduction through the tissue to body surface. In individuals with spinal cord injury (SCI) autonomic disruption, immobility and inactivity play critical roles in affecting peripheral vascular circulation. It is even more important to monitor temperature changes during the physical activity (rehabilitation process) in mentioned group of patients. One of the possible ways how to provide thermometric measurements and evaluation is the use of the infrared (IR) thermography. It is very important to use suitable methodology of measurement. IR imaging can produce reliable and valid results only if the technique follows established standards. Initial thermographic measurements in SCI individuals and able-bodied (AB) during the rehabilitation process were performed. PMID- 17281850 TI - Monitoring and assessment of cardiovascular regulation in spinal cord injured patients. AB - Spinal cord injured patients suffer from unstable regulation of their cardiovascular function due to nerve damage caused by the injury. Currently there is no well established method for continuous monitoring and assessment of cardiovascular regulation in spinal cord injured patients during rehabilitation. Therefore, a design for a cardiovascular regulation monitoring device capable of detecting blood flow is proposed in this study. The proposed design is based on using Photoplethysmographic (PPG) sensors which detect the fluctuations of light absorption in tissue during blood flow. These fluctuations oscillate at the heart cycle rate owing to the cardiac induced increase in the tissue blood volume during systole. Using the device, heart rate variability, and variations in the PPG signal (both amplitude and baseline which reflect the vessels compliance and blood flow) are analysed to assess the cardiovascular regulation function. The sensors may be located at different body sites and therefore allow inspection of the correlation of blood flow at various body locations, thus assessing the tone of the variations from a central origin in SCI patients. The described device has been designed for early clinical investigation and test results demonstrate that it has the capabilities of providing quantitative assessment of spinal cord injured patient's cardiovascular regulation. PMID- 17281852 TI - A suite of computer-assisted techniques for assessing upper-extremity motor impairments. AB - this paper presents the design and implementation of a suite of computer-assisted rehabilitation platform techniques that are intended especially for individuals with upper-extremity motor impairments. It utilizes force-reflecting and other devices to provide interactive upper limb assessment and therapy. It includes a rich menu of user-centered performance assessment capabilities, and includes support for telerehabilitation links, for protocol design, and for data analysis. Preliminary results of its use as a research tool for several projects are presented and discussed. PMID- 17281853 TI - The accuracy of surface measurement for motion analysis of osteoporotic thoracolumbar spine. AB - The surface method of measuring the movements of lower thoracic and lumbar spine with osteoporosis using Fastrak® was examined for validity. There is an increasing awareness of the health risks of exposure to radiation associated with repeated radiographic assessment of spinal curvature and spinal movements. As a skin-surface measurement device, Fastrak® was employed to study the effect of low bone mineral density on spine motion. However, the reliability and validity of data recorded has not been established. The purpose of this study was to develop a methodology to determine the accuracy of the surface measurement device when it is applied to the motion analysis of osteoporotic spine. The results obtained indicated that the rotation angle of lumbar and lower thoracic spine could be predicted with acceptable accuracy from the data collected from skin-mounted sensors, while the prediction error of translational movements were not acceptable. PMID- 17281854 TI - Multi-segment foot motion analysis on hallux valgus patients. AB - In this study, a multi-segment foot motion analysis on hallux valgus patients were performed using the 9-segment foot model and then compared with the results from normal subjects. Results showed that there were no significant differences in hindfoot motions between normal subjects and HV patients. However, noted in HV patients were hyperexternal rotation in the talocrural joint, an excessive eversion of the subtalar joint during early stance and lack of dynamic motion in hallux MP and medial MP joints especially during terminal stance. In spite of limitation in this study due to the small number of HV patients, the current multi-segment foot model would be feasible to diagnose and treat patients with various foot diseases, combined with further studies in the future. PMID- 17281855 TI - An upper-limb-movement classification system of cerebral palsy children based on arm motion detection. AB - The researches about upper limb palsy patients are the minority areas among the researches about cerebral palsy (CP) patients. This paper presents an upper-limb movement classification system of cerebral palsy children based on their arm motion information to judge their impairment degree. The system contains three parts: image capture, image segmentation, and information classification processing. Momentum analysis parameters and coordination neural network are used to conduct the data classification. The experimental results are shown that the proposed system has the higher accurate rate of tracking compared with Normalized Cross Correlation and Otsu methods, and the patients are divided into the slight impairment grade or the serious impairment grade. PMID- 17281856 TI - Foot-Ankle Roll-Over Characteristics in Different Heel Heights during Walking. AB - In this study, a feasibility study was performed for biomechanical applications of foot-ankle roll-over characteristics in different heel height shoes during walking. Five nondisabled female volunteers were participated in gait experiments, wearing four pairs of shoes with different heel heights. Roll-over shapes of the foot-ankle systems were obtained using trajectories of ankle, knee and the center of pressure between initial contact (IC) and opposite initial contact(OIC). Results showed that roll-over trajectories moved downwards with higher heel shoes but roll-over characteristics, represented by an arc, did not change significantly with different heel heights. The present results also support that nondisabled humans automatically adapt their foot-ankle systems to varying heel height shoes under 6cm. Roll-over characteristics in human walking will contribute future designs of prosthetics and orthotics of lower extremity as well as orthopaedic shoes. PMID- 17281857 TI - Application of nonlinear dynamics to human postural control system. AB - Instability, fear of falling and fall injuries are common problems for the older population and individuals with chronic disabilities. Development of screening tools and outcome measures of balance performance and fall risk has become of great interest for health professionals and researchers in the field of rehabilitation. Although linear modeling is desirable due to its simplicity, however, most physiological systems are too complicated to lend themselves to linear analysis because the human body is multi-segmental, and there are feedforward and feedback control schemes of mutual relationship between the segments. In this study, we investigated the use of nonlinear dynamic tools to extract characteristic features of postural sway. Among various methods of nonlinear dynamics, the Renyi fractal dimension and the Renyi spectrum are presented as quantitative descriptors. The center of foot pressure (COP) was recorded during four quiet standing tasks of increasing difficulty (eliminating vision and use of a compliant surface). The COP trajectories' Renyi dimension and Renyi spectra of young healthy subjects with no history of neurological disorder were investigated in comparison to that of elderly patients with balance impairment and history of frequent falls. Sway path, the common linear parameter of postural sway, was also used to investigate its distinction from non-linear parameters. The results of this study suggest the COP trajectories' Renyi dimension and sway path can be used as classifiers for balance disorders, and they provided different indications of postural control system characteristics between the two groups and different task demands. PMID- 17281858 TI - The assessment of ankle joint forces during the postural balance control movement. AB - The purpose of this study was to calculate three-dimensional angular displacements, moments and joint reaction forces of the ankle joint during the waist pulling, and then, we assessed the reaction forces and bone-on-bone forces within ankle joint during postural balance control movement. With experiments and MATLAB simulation we could calculate ankle joint kinematic and kinetic data. The results presented in this study will be useful data for understanding the injury mechanism of ankle joint during postural balance control. PMID- 17281859 TI - Development of an interactive motivating tool for rehabilitation movements. AB - In this paper, an interactive tool, including three computer games controlled via the center of foot pressure (COP) trajectory biofeedback, was designed to aid in pressure balance for rehabilitating persons with balance disorders. The games interact in real-time with the Vista Medical Force Sensitive Applications software and pressure mat. The main goal of this research was to employ attractive and motivational learning techniques, using equipment that is available to a large population, to increase volume of exercise practice and to retain the patient's attention. Questionnaires regarding the motivational aspects of the games were administered to 15 subjects (7 patients). The results indicate that the tools were indeed attractive, motivational and an improvement to conventional exercise regimes. PMID- 17281860 TI - A wheelchair usage monitoring/logging system. AB - Real life information on wheelchair usage is important for investigating the effectiveness of certain features, evaluate users' performance, and eventually improve the safety and reliability of wheelchairs. The purpose of the study is to develop a wheelchair usage monitoring/logging system that travels with wheelchair users in their daily activity settings and collects data independently. The system consists of a wheel rotation logging module, a GPS logging module, and a seating posture logging module. It obtains data on how far wheelchair users drive, where they have been, and how long they spend in various seating positions. The initial testing results showed that the system can be used as a clinical compliance tool to determine how clients are using their wheelchairs, and if they are effectively using seat features to relieve seating pressure. PMID- 17281862 TI - Analysis of trunk movement in orthotic gait of paraplegics. AB - In an orthotic gait of paraplegics, a leg restriction and motor paralysis result in a significant loading. In this study, we address to quantify a relationship between the loading, leg restriction and motor paralysis, and analyze lumbar joint trajectories in the orthotic gait of paraplegic subjects and the ordinary and orthotic gaits of a normal subject using an inverted pendulum model. For the leg restriction, the trajectories are located anterior to an equilibrium point of the inverted pendulum, and the loading is higher due to the influence of gravity moment. Comparing the orthotic gait kinematics of paraplegic with that of normal in the horizontal plane, the lumbar joint trajectory in the paraplegic subjects was rectilinear shape, while that in the normal subject was curved in the direction to the equilibrium point. The loading is lower in the curved trajectory than in the straight trajectory because of the trade-off between gravity and inertia. These results suggest that the leg restriction and motor paralysis lead to the increase of the distance between the trunk movement and the equilibrium point of an inverted pendulum, which causes significant loading in the orthotic gate of paraplegics. PMID- 17281861 TI - New shape memory alloy actuator: design and application in the prosthetic hand. AB - This paper describes a new SMA actuator design and its application in the prosthetic hand replacing conventional servo motors which are bulky and noisy in nature. Two one-way memory SMA wires are used in the development of the actuator. The proposed actuator consists of two 0.3mm in diameter SMA wires inserted from both ends of a stainless outer tube which functions as a guide and simultaneously a heat sink for the dissipation of heat from the SMA. These wires meet at the centre of the stainless tube where an electrode is placed. There are 2 other electrodes, each located at the end of the outer tube. These electrodes are the points where current is passed through each of the SMA wire asynchronously. In order to actuate a degree of freedom (DOF) of a robotic finger, 2 actuators are used each for the flexion and extension actions respectively. A high voltage PWM signal of very short intervals is used in actuation to avoid excessive heat build up in the SMA due to long unnecessary heating. PMID- 17281863 TI - Tactile substitution system for transmitting a few words to a prosthetic hand user. AB - This paper describes an efficient system for transmitting a few words (verbal information) to a prosthetic hand user by using a two-channel electrotactile stimulation capable of generating apparent movements, which is applied to the upper arm area of the left hand via surface concentric electrodes. If the prosthetic hand user gets verbal information about interaction between the prosthesis and the environment, e.g., the prosthetic hand just touched a doorknob, he/she will be able to open or close the door even in the darkness, and also to handle an object on the top of a shelf out of his/her view. In this study, verbal information was provided regarding which finger touches the object (three states), and the fingers angle (two states). Consequently, six states of verbal information could be sent. We therefore designed five stimulation patterns (duration 600 - 800 ms) comprising several burst profiles in which each burst was composed of several pulses (interval of biphasic pulses, 2.85 ms) modulated in amplitude. The recognition experiments using 10 healthy subjects showed that the mean percentage of recognition was about 94% (standard deviation: 3.9). These results suggested the possible applicability of the proposed system to assist prosthetic hand users. PMID- 17281864 TI - A dynamic tactile map as a tool for space organization perception: application to the design of an electronic travel aid for visually impaired and blind people. AB - This paper addresses a new concept of visuotactile human-machine interface for a certain representation of the peripersonnal space, especially useful for visually impaired and blind people navigation. The proposed space representation have been successfully implemented on a tactile device and validated via series of experiments involving naive blindfolded sighted people. Results show that is possible to interact with the space via the proposed tactile representation. PMID- 17281865 TI - The Influence of Dynamic Trans-tibial Prosthetic Alignment on Standing Plantar Foot Pressure. AB - In order to study quantitative effect of dynamic prosthetic alignment on standing biomechanical property for trans-tibial amputees, plantar foot pressure of one subject during natural standing were recorded by using the Pedar in-shoe pressure measurement system with different alignment angles in the sagittal and frontal planes. The results showed that angular alignment had significant effects on the foot pressure distribution and magnitude of prosthetic side. Peak pressure on prosthetic foot was 1.96 times larger than the one on sound foot, although only about 38% body weight was supported by prosthetic side on average. Adjustment of alignment angle in sagittal and frontal planes made the center of pressure on foot shift in A/P and M/L directions respectively. The findings provide potentially useful information for prosthesis design and biomechanical analysis of lower limb. PMID- 17281866 TI - Study on the Effects of Electrical Stimulation on the Pattern Recognition for an EMG Prosthetic Application. AB - The need of biofeedback in Man-Machine interfaces is of vital importance for the development of subconscious control with external devices. In order to obtain extended proprioception, in other words, to include the external devices into the body schema, we need to provide with more feedback channels to the human body. In this study we look into the use of electrical stimulation as biofeedback and its effects over the pattern recognition process from the EMG signals that controls the hand movements. PMID- 17281867 TI - Interferential current stimulation for sensory communication between prosthetic hand and man. AB - Our purpose is to clear whether the interferential current (IFC) method is useful for information transmission of a myoelectric prosthetic hand to the user. IFC stimulation is composed of two AC output waves. In previously, we demonstrated that IFC method using the two waves with different frequencies could vary the intensity of perceived stimulus. In the present study, we evaluated that the relationship between a movement of position of perceived stimulus and IFC method, using two waves with the same median frequency and a different phase. Moreover, we investigated the effects of a distance of recording electrodes from stimulating electrodes on a degree of interference of IFC with EMG signals. The movement of position of perceived stimulus was caused by the phase difference changing. IFC interfered with EMG signals. Especially, the interference of IFC with EMG of the muscle under stimulating electrodes was large. In contrast, when recording electrodes was distant from the stimulating electrodes, the interference of IFC was small. Moreover, the interference was eliminated by the low-pass filter (< 500Hz). These results support the usefulness of a combination of the IFC method with EMG recording system equipped with the low-pass filter as a sensory feedback system for myoelectric prosthetic hand. PMID- 17281868 TI - Safety assurance of assistive devices based on a two-level checking scheme. AB - The increasing number of physically challenged individuals has boosted the demand of powered wheelchairs. This paper is on the subject of a DSP (Digital Signal Processors) based assistive system, which is associated with a two-level checking scheme. The assistive system takes on the M3S (Multiple Master Multiple Slave) regulation for the assurance of safety. The CAN (Control Area Networks) embedded module in the DSP provides robust transmission of information within the system. The hardware interfaces based on the two-level checking scheme is implemented in input devices (e.g. joystick, head control apparatus) and in output devices (e.g. manipulator, prime mover motors). PMID- 17281869 TI - The feature-based modeling of standard tooth in a dental prosthetic database. AB - This paper presents a feature-based approach that creates standard teeth models in database to provide the topological construction of the model for dental CAD. The approach arises from the basic idea that every tooth has its individual features and can be implemented in three steps. In the first step, the features on teeth are defined according to the oral anatomy. In the second step, Nurbs surfaces are applied so that the forms of standard teeth can be represented via establishing the topological relationship of features. Here, these feature-based surfaces have the capability of being local controlled that guarantees the accuracy of dental design. In the last step, feature curves are presented to describe the topological construction of dental ridges and grooves. Through these curves, the occlusal surface can be changed globally, simplifying dental design. It is finished with the establishment of standard database composed of 28 standard models constructed by feature-based surfaces and feature curves. PMID- 17281870 TI - Design, construction and evaluation of an electromechanical stance-control knee ankle-foot orthosis. AB - A new electromechanical Stance-Control Knee-Ankle-Foot Orthosis (SCKAFO) was designed to provide improved gait for people with knee-extensor weakness. This SCKAFO inhibits knee flexion at any knee angle while allowing knee extension during weight bearing. During swing or other non-weight bearing activities, the SCKAFO allows free knee motion. A prototype joint was mechanically tested to determine the moment at failure, loading behaviour, and device safety. Quantitative kinematic gait analysis of three able-bodied subjects and three knee anklefoot-orthosis (AFO) users showed that the new SCKAFO had a desired minimal effect on able-bodied walking gait. The SCKAFO permitted a mean increase in sagittal knee motion (488%) during swing for the three KAFO users and a reduction in pelvic obliquity and hip abduction angle abnormalities during terminal stance and swing for two KAFO users. PMID- 17281871 TI - Comparative study on artificial neural network with multiple regressions for continuous estimation of blood pressure. AB - There are many studies about cuffless and continuous blood pressure estimation using pulse transit time (PTT). In this study, we proposed the modeling method which could estimate systolic BP (SBP) conveniently and indirectly using PTT and some biometric parameters. 45 people participated in this study and we measured PTT using photoplethysmography (PPG) and electrocardiogram (ECG) signals and biometric parameters such as weight, height, body mass index (BMI), length of arm and circumference of arm. Before modeling, we selected variables as predictors using statistical analysis. With these parameters, we compared artificial neural network (ANN) with multiple regressions as an estimating method of BP. We evaluated the mean differences and standard deviations between estimated value and reference value, acquired from a KEDA-approved device. The results showed that the ANN had better accuracy than the multiple regression. ANN's estimation satisfied AAMI standard as a BP device. PMID- 17281872 TI - Design and implementation of deformation algorithms for computer assisted orthopedic surgery: application to virtual implant database and preliminary results. AB - In cranio-maxillofacial and in trauma surgery while making osteosynthesis the surgeons want to reposition bone fractures and make fixation using implants and fixations devices. These devices need to be bent during surgery or prior surgery to fit geometrical boundary conditions defined by the individual anatomy of the patient. In clinical routine, surgeons must frequently repeat several times the "bend and try" process until they get the best fitting. This process often requires up to twenty minutes for a single osteosynthesis plate. A realistic deformation algorithm is then a pre-requisite to a computer-aided planning system which aims to help surgeons to optimally pre-bend the implant in respect to an individual patient bone structure. It has been shown that computer assisted planning system for bendable implant improves the results and operation outcome: shorter operation time, more accuracy, less post-operative implant failure, etc. This paper presents our preliminary results on implementing different types of deformation algorithms in the context of computer assisted orthopedic surgery. PMID- 17281873 TI - Computerized Classification Method for Differentiating Between Benign and Malignant Lesions on Breast MR Images. AB - Contrast-enhanced breast MRI has been shown to have very high sensitivity in the detection of breast cancers. A new computerized classification method for differentiating between benign and malignant lesions on breast MRIs was developed. This method was based on temporal feature analysis. We experimented with a set of thresholds of the contrast uptake and washout speed to automatically determine suspicious malignant areas. An angiogenesis map was generated to indicate suspicious malignant areas by color. The results obtained from the retrospective analysis on 64 malignant and 29 benign breast lesions showed that our method achieved 90.5% (57/63) sensitivity in detecting malignant lesions, and it correctly classified 55% (16/29) benign lesions as benign. The study results demonstrated the effectiveness of this temporal feature analysis method for the detection of malignant lesions and its performance in delineating malignant lesions from benign lesions. PMID- 17281874 TI - Developing a DICOM Middleware to Implement ECG Conversion and Viewing. AB - Nowadays, medical environment is integrated and complicated, involving large amounts of various medical data, such as images, waveforms and other digital data. For the interoperability of images and waveforms in imaging context, the images and waveforms usually need to be interchanged and stored using one standard. DICOM is the best choice, which is an international standard for the communication and storage of medical information. In this paper, we developed a DICOM middleware with capability of converting SCP-ECG, the European standard for resting ECGs, into DICOM ECGs. Then an ECG viewing component is implemented, which can parse and display SCP-ECG records and DICOM ECGs. The research results show that our work can realize seamless workflows in multi-vendor environment, contribute to the harmonization of ECG standards, and facilitate digital ECG applications. PMID- 17281875 TI - The architecture of enterprise hospital information system. AB - Because of the complexity of the hospital environment, there exist a lot of medical information systems from different vendors with incompatible structures. In order to establish an enterprise hospital information system, the integration among these heterogeneous systems must be considered. Complete integration should cover three aspects: data integration, function integration and workflow integration. However most of the previous design of architecture did not accomplish such a complete integration. This article offers an architecture design of the enterprise hospital information system based on the concept of digital neural network system in hospital. It covers all three aspects of integration, and eventually achieves the target of one virtual data center with Enterprise Viewer for users of different roles. The initial implementation of the architecture in the 5-year Digital Hospital Project in Huzhou Central hospital of Zhejiang Province is also described. PMID- 17281876 TI - Detection of colon cancer by laser induced Fluorescence and Raman spectroscopy. AB - Laser-induced fluorescence and Raman spectroscopy of serum for detect colon cancer was investigated in this paper. The difference to serum spectrum was discovered. Three Raman peaks were consistently observed from normal blood serum emission using 488.0nm and 514.5nm excitation of an Ar-ion laser. While no Raman peak or slight Raman peaks were detected from colon cancer's cases. In addition, the red shift of fluorescence peak and decrease of fluorescence intensity are founded after samples radiated by laser. 65 colon cancer cases are investigated in this paper. Through three parameters we obtained an accuracy of 83.5% compared to clinical diagnosis. These results have important reference values to explore the method of Raman spectrum and for diagnosis of cancer. PMID- 17281877 TI - Meanaging Knowledge for the emergency care of heart attack patients: Paramedics and thrombolytic treatment. AB - The objective of this paper is to examine the Knowledge Management(KM) paradigm in the context of UK paramedics' assessment and treatment of patients with suspected acute myocardial infarction (MI) or ;heart attack' We outline the role of thrombolytic therapy and other aspects of emergency cardiac care and discuss how contemporary KM tools and techniques can be used to support the development and retention of key clinical skills and knowledge in this emerging field of parcice. PMID- 17281878 TI - A team agent approach to postmarketing surveillance of adverse drug reactions. AB - Current postmarketing surveillance methods largely rely on spontaneous reports which suffer from serious underreporting, latency, and inconsistent reporting. Thus they are not ideal for rapidly identifying rare adverse drug reactions (ADRs). We propose an active, multi-agent computer software system, where each agent is empowered with teamwork capabilities such as anticipating information needs, identifying relevant ADR information, and continuously monitoring and proactively sharing such information in a collaborative fashion with other agents. The main purpose of this system is to help regulatory authorities (e.g., FDA in the U.S.) find previously unrecognized ADRs as early as possible. Another objective is to promote increased filing of on-line ADR reports thereby, addressing the severe underreporting problem with the current system. The proposed system has the potential to significantly accelerate the process of ADR discovery and response by utilizing electronic patient data distributed across many different sources and locations more effectively. Our preliminary system design is presented and some issues related to it are discussed. PMID- 17281879 TI - Towards a web-based knowledge management system for cardiovascular disease. AB - The objective of this paper is to examine the efficacy of the Knowledge Management (KM) paradigm for a web-based patient administration system (PAS) for cardiovascular disease (CVD). We discuss the role of contemporary information and communication technologies (ICTs) for the management of electrocardiographic information and how this can act as a foundation for a KM-based system. PMID- 17281880 TI - Rough Set Based Classification rules generation for SARS Patients. AB - SARS is an acute infectious disease and can cause a large amount of death. Up until now we have not known it well. With the experimental results of micronutrients of 30 SARS patients and 30 non-SARS patients, using rough set theory we induce some classification rules. Attribute reduction results show that micronutrients Fe, Ca, K and Na are necessary and sufficient for classification, whereas micronutrients Zn, Cu and Mg are not necessary or are redundant. Additionally, we find that micronutrient Ca has a strong correlation to SARS. The classification results of 30 other examples show that the rough set classification method is available. PMID- 17281881 TI - Changes in multifractality with aging and heart failure in heartbeat interval time series. AB - We present a multifractal analysis of diurnal heart interbeat time series from healthy young subjects, healthy elderly subjects and patients with congestive heart failure (CHF). Aging and CHF causes loss of multifractality. We analyze the multifractal spectrum asymmetry. We show that the joint analysis of the degree of multifractality and the asymmetry parameter can differentiate between the cardiac interbeat time series of young and elderly persons and it can also separate healthy subjects and CHF patients. PMID- 17281882 TI - Detecting brain activity variation of rat during anesthesia by spectral entropy. AB - In order to detect and measure the brain activity variation under different depth of anesthesia (DOA), the Spectral Entropy (SE) of electroencephalogram (EEG) of the SD rat was studied in this paper. The SE of EEG was measured under different DOA and the relationship between SE and the DOA was analyzed. The SE of EEG will decrease quickly while the DOA is from light to deep and vice versa, so it can be used to distinguish light and deep anesthesia, but it can not distinguish awake and light anesthesia accurately. Compared with power spectrum, we can see the change of SE is opposite to that of power spectrum. Besides EEG SE analysis, the SE variations of four rhythms of EEG (delta, theta, alpha and beta) also are analyzed. The study shows SE of delta rhythm dynamic change leads to the change of EEG and the delta rhythm is the dominant rhythm of rat during anesthesia. PMID- 17281883 TI - Assessment of swallowing sounds' stages with hidden markov model. AB - Swallowing sounds analysis has received much attention recently due to its diagnostic potentials. The process of swallowing is one of the most complicated mechanisms of the body, in which a few different events are occurred in a few milliseconds. The timing and coordination of these events within a breath cycle is crucial for a safe swallow to occur. In order to improve our ability to treat swallowing disorder and to create non-invasive acoustical diagnostic methods, we must develop a detailed understanding of how the swallowing sounds are produced and what the contribution of each swallowing event is to the sounds that are heard and recorded as swallowing sounds. This paper presents a Hidden Markov Model (HMM) of the swallowing sounds, in which it is shown for the first time that the swallowing sounds have three stages. The number of stages was found to be very consistent between the subjects and the bolus textures implying the robustness and fitness of the model. PMID- 17281884 TI - Determination of the Chromatic Contrast Responses using Wavelet Analysis of Visual Evoked Potentials. AB - In order to test the human color vision objectively, we have developed the technique using the sweep parameter VEP technique (Norcia and Tyler, 1985) with an iso-luminant chromatic grating is effective to detect the defective color vision (Momose and Saito, EMBC2002). In this study, the wavelet transform using complex Morlet wavelet was examined to detect the dynamical spectrum of VEP in color vision defectives. Vertical sinusoidal iso-luminant chromatic gratings (6 Hz, 2 c/deg) presented on a color monitor were used as stimuli. The two colors for the gratings were selected from the colors on the dichromatic iso-chromatic lines. Steady-state VEPs were recorded during a continuous decrease of chromatic contrast at 10%/s. VEP components at 12 Hz and 16 Hz were evaluated as the response signal and background EEG (noise), respectively. For deuteranopic iso chromatic colors, the signal to noise ratio (SNR) of deuteranope and deteranomalia were significantly lower than those of normals (P<0.01), indicating that this technique is effective for objectively detecting of the color vision defectives. PMID- 17281885 TI - Heart rate variability in subjects with different hypnotic susceptibility receiving nociceptive stimulation and suggestions of analgesia. AB - The aim of the present study was to investigate the possible hypnotizability related modulation of heart activity during nociceptive stimulation (pressor pain) and during nociceptive stimulation associated with the suggestion of analgesia in not hypnotized healthy individuals with a high (Highs) and a low (Lows) hypnotic susceptibility. ECG and respirogram were recorded. Standard time and frequency domain indexes were evaluated, together with the sd1 and sd2 values of the Poincare plot over the RR series. Results showed self reports of analgesia in Highs and a significant increase of the respiratory frequency during stimulation in both groups. Very few significant differences between groups and among conditions were detected for mean RR and heart rate variability (HRV) through spectral analysis. and through the Poincare indexes evaluation. On the contrary, a promising approach seems to be the study of the correlations among standard and Poincare variables. In particular, different changes in (or even lost of) correlations were enlightened in Highs and Lows, suggesting a different modulation of RR in the two groups, probably due to the very low frequency components of HRV. Different roles of sympathetic and parasympathetic activities during stimulation can be suggested. PMID- 17281886 TI - Glottal Waves via Inverse Filtering of Vowel Sounds. AB - This paper shows how to obtain accurate glottal waves via inverse filtering of vowel sounds and how to determine if these glottal waves contain any significant resonance of vocal tracts. We obtain vocal-tract filter (VTF) estimates for the inverse filtering from sustained vowel sounds over closed glottal phases using a new method, which minimizes the effects of glottal waves on the VTF estimates. It is common that VTF estimates contain the effects of incomplete glottal closures, and the glottal waves obtained via inverse filtering contain residual vocal-tract resonance. Our simulations show that the residual resonance appears as stationary ripples superimposed on the derivatives of the original glottal waves over the duration of a glottal cycle. The VTF estimates and the glottal waves obtained from sustained vowel sounds /a/ produced by male and female subjects are presented. The derivatives of the obtained glottal waves exhibit transient positive peaks during vocal-fold collision and negative levels in the earlier stage of vocal-fold parting. PMID- 17281887 TI - Myocardial Fiber Length Mapping with MR Diffusion Tensor Imaging. AB - Diffusion tensor MRI is emerging as a rapid, nondestructive method to map myocardial fiber organization. A precise biological description of myocardial fiber performance requires knowledge of four variables: length, force, velocity and time. However, study of quantification of myocardial fiber length is lacking. The current study aims to show myocardial fiber length maps of formalin-fixed heats. Diffusion tensor MRI with medium diffusion resolution (15 directions) was performed in one isolated pig heart. Fiber length maps were investigated in multiple short-axis slices. The results provide supplementary information of myocardial fiber organization. To our knowledge, the present study is the first report of the myocardial fiber length mapping. PMID- 17281888 TI - Study on a fully open magnetic resonance imaging device with a slice imaging region. AB - A new unilateral permanent magnet configuration for magnetic resonance imaging (MRI) system producing a slice imaging region with field homogeneity is presented. It is a totally new problem about magnet design to build a slice imaging region with homogeneous magnetic field outside the magnet source. A novel design method with high precision is proposed here to probe the existence possibility of such a remote slice region and then is used to analyze the location and size of the slice region. The success of such a unilateral permanent magnet with a slice region for MRI builds a strong basis for some scientific research such as the construction of the unilateral MRI system with homogeneous magnetic field. PMID- 17281889 TI - Assessment of Adipose Tissue from Whole Body 3T MRI Scans. AB - Accurate assessment of total body and the distribution of regional adipose tissue is a critical problem emerging in the United States. Using manual segmentation of MRI scanned images is a problem due to the high variation between manual delineations. Manual segmentation also requires highly trained experts with knowledge of anatomy. In this study, we used a specific water saturation sequence and histogram based segmentation method that provides robust delineation results for adipose tissue from whole body MRI scans. Both phantom and human subject studies were performed. Compared with a standard clinical T1-weighted acquisition, our method appears to give superior quantitative results. PMID- 17281890 TI - Comparative Study of Symmetric and Asymmetric Cylindrical MRI Gradient Y-Coils in terms of Induced Eddy Currents. AB - We have recently introduced the concept of whole-body asymmetric MRI systems [1]. In this theoretical study, we investigate the PNS characteristics of whole-body asymmetric gradient systems as compared to conventional symmetric systems. Recent experimental evidence [2] supports the hypothesis of transverse gradients being the largest contributor of PNS due to induced electric currents. Asymmetric head gradient coils have demonstrated benefits in the past [3]. The numerical results are based on an anatomically-accurate 2mm-human voxel-phantom NORMAN [4]. The results of this study can facilitate the optimization of whole-body asymmetric gradients in terms of patient comfort/safety (less PNS), while prospering the use of asymmetric MRI systems for in-vivo medical interventions. PMID- 17281891 TI - Mechanical shear wave induced by piezoelectric ceramics for magnetic resonance elastography. AB - Magnetic resonance elastography (MRE) is a noninvasive technique to measure elasticity of tissues in vivo. For MRE, an additional actuator is needed to be mounted on an observed object, and to excite the object. In this paper, an experiment is set to obtain MR mechanical shear wave images. A novel actuator is proposed to generate mechanical wave propagating inside a gel phantom. The actuator is made of piezoelectric ceramics, and is fixed on a plexiglass bracket. Both of the gel phantom and the actuator are put into a head coil in the scanner's bore. The actuator works synchronously with an imaging sequence running on the scanner. The sequence is modified from a FLASH sequence, into a motion sensitizing phase-contrast sequence, for shear wave imaging. Wave images are presented to show the effect of those factors, such as the stiffness of the phantoms, the frequency of the actuator, the parameters of the motion-sensitizing gradient, and the oscillation of the patient bed. PMID- 17281892 TI - fMRI-Compatible Electromagnetic Haptic Interface. AB - A new haptic interface device is suggested, which can be used for functional magnetic resonance imaging (fMRI) studies. The basic component of this 1 DOF haptic device are two coils that produce a Lorentz force induced by the large static magnetic field of the MR scanner. A MR-compatible optical angular encoder and a optical force sensor enable the implementation of different control architectures for haptic interactions. The challenge was to provide a large torque, and not to affect image quality by the currents applied in the device. The haptic device was tested in a 3T MR scanner. With a current of up to 1A and a distance of 1m to the focal point of the MR-scanner it was possible to generate torques of up to 4 Nm. Within these boundaries image quality was not affected. PMID- 17281893 TI - Automatic Quantitative Analysis of Myocardial Wall Motion and Thickening from Long-and Short-Axis Cine MRI Studies. AB - This work presents a fully automatic method for regional myocardial contraction and motion assessment in cardiac cine MRI studies. The prerequisite of segmenting the left ventricle at all temporal phases of the study, is accomplished using a statistical model-based algorithm (3D- ASM). Subsequent functional analysis includes the assessment of LV global functional indexes like e.g. time-volume curves, ejection fraction, stroke volume and cardiac output, as well as regional function parameters, like segmental wall motion, thickening and dyssynchrony delays. PMID- 17281894 TI - Use of a voxelwise approach in the analysis of fractional anisotropy data in multiple sclerosis patients. AB - Diffusion tensor magnetic resonance imaging (DTI) has the ability to provide non invasive information on tissue microstructure not available in routine clinical MRI images. This includes information regarding the degree of anisotropy as well as the direction of the diffusion of water molecules within the tissues. Since white matter areas of the brain have an ordered structure (due to the myelination and directionality of axons) and thus a high degree of anisotropy, the ability to detect changes in anisotropy can be extremely useful in the study of diseases such as multiple sclerosis (MS), which involves the demyelination of axons. Several studies have used DTI to investigate well defined MS lesions as well as normal appearing white matter (NAWM) lesions not seen in conventional MR images. These studies have typically used region of interest (ROI) based approaches to analyze the data. However, studies using ROI based analysis techniques have several drawbacks. These include the time required to draw ROIs, the reproducibility of these ROIs, and the accuracy of placement of these ROIs, especially in NAWM regions where there is no a priori knowledge of the presence or absence of MS lesions. In this study, we have demonstrated the utilization of a semi-automated method for performing a voxelwise analysis in the detection of MS lesions. PMID- 17281895 TI - Vector-valued local frequency representation for robust multimodal image registration. AB - Automatic registration of multi-modal images involves algorithmically estimating the coordinate transformation required to align the data sets. Most existing methods in literature are unable to cope with registration of image pairs with large non-overlapping field of view (FOV). We propose a robust algorithm, based on matching vector-valued local frequency (corresponding to the dominant local frequency magnitude) image representations, which can cope with image pairs with large non-overlapping FOV. The work reported here is an extension of our earlier work which used dominant local frequency magnitude based representations of the input data as input to the matching algorithm. The local frequency representation naturally allows for processing the data at different scales/resolutions, a very desirable property from a computational efficiency view point. Our algorithm involves minimizing - over all affine transformations - the integral of the squared error (ISE or L2E) between a Gaussian model of the residual and its true density function. The residual here refers to the difference between the local frequency representations of the transformed (by an unknown transformation) source and target data. We present implementation results for misalignments between MR brain scans obtained using different image acquisition protocols. PMID- 17281896 TI - Wavelet Based Characterization of Vertebral Trabecular Bone Structure from MR Images of Specimen at 3 Tesla Compared to MicroCT Measurements. AB - Trabecular bone structure and bone density contribute to the strength of bone and are important in the study of osteoporosis. Wavelets are a powerful tool to characterize and quantify texture in an image. In this study the thickness of trabecular bone was analyzed in 8 cylindrical cores of the vertebral spine. Images were obtained from 3 Tesla (T) magnetic resonance imaging (MRI) and micro computed tomography (μCT). Results from the wavelet based analysis of trabecular bone were compared with standard two-dimensional (2D) structural parameters (analogous to bone histomorphometry) obtained using mean intercept length (MR images) and direct three-dimensional (3D) distance transformation methods (μCT images). Additionally, the bone volume fraction was determined from MR images. We conclude that the wavelet based analyses delivers comparable results to the established MR histomorphometric measurements. The average deviation in trabecular thickness was less than one pixel size between the wavelet and the standard approach for both MR and μCT analysis. Since the wavelet based method is less sensitive to image noise, we see an advantage of wavelet analysis of trabecular bone for MR imaging when going to higher resolution. PMID- 17281897 TI - MRI and image quantitation for drug assessment - growth effects of anabolic steroids and precursors. AB - MRI and image quantitation play an expanding role in modern drug research, because MRI offers high resolution and non-invasive ability, and provides excellent soft tissue contrast. Moreover, with development of effective image segmentation and analysis methods, in-vivo and serial tissue growth measurements could be assessed. In the study, MR image acquisition and analysis protocol were established and validated for investigating the effects of anabolic steroids and precursors on muscle growth and body composition in a guinea pig model. Semi automatic and interactive segmentation methods were developed to accurately label the tissue of interest for tissue volume estimation. In addition, a longitudinal tissue area outlining procedure was proposed for study of tissue geometric features in relation to tissue growth. Finally, a fully automatic data retrieval and analysis scheme was implemented to facilitate the overall huge amount of image quantitation, statistical analysis, as well as study group comparisons. As a result, highly significant differences in muscle and organ growth were detected between intact and castrated guinea pigs using the selected anabolic steroids, indicating the viability of employing such protocol to assess other anabolic steroids. Furthermore, the anabolic potential of selected steroid precursors and their effects on muscle growth, in comparison with that in respective positive control groups of castrated guinea pigs, were evaluated with the proposed protocol. PMID- 17281898 TI - Validation techniques for quantitative brain tumors measurements. AB - Quantitative measurements of tumor volume becomes more realistic with the use of imaging- particularly specially when the tumor have non-ellipsoidal morphology, which remains subtle, irregular and difficult to assess by visual metric and clinical examination. The quantitative measurements depend strongly on the accuracy of the segmentation technique. The validity of brain tumor segmentation methods is an important issue in medical imaging because it has a direct impact on many applications such as surgical planning and quantitative measurements of tumor volume. Our goal was to examine two popular segmentation techniques seeded region growing and active contour "snakes" to be compared against experts' manual segmentations as the gold standard. We illustrated these methods on brain tumor volume cases using MR imaging modality. PMID- 17281899 TI - Bayesian Method for Continuous Cursor Control in EEG-Based Brain-Computer Interface. AB - To develop effective learning algorithms for continuous prediction of cursor movement using EEG signals is a challenging research issue in Brain-Computer Interface (BCI). To train a classifier for continuous prediction, trials in training dataset are first divided into segments. The difficulty is that the actual intention (label) at each time interval (segment) is unknown. In this paper, we propose a novel statistical approach under Bayesian learning framework to learn the parameters of a classifier. To make use of all the training dataset, we iteratively estimate probability of the unknown label, and use this probability to assist the training process. Experimental results have shown that the performance of the proposed method is equal to or better than the best results so far. PMID- 17281900 TI - Artifacts, habituation and p300-based brain machine interfaces. AB - We investigated to what degree the detection rate of the P300 in single trial event-related potentials is affected by short-term and long-term habituation effects, and we present an algorithm to eliminate eye-movement artifacts. Data from 26 subjects were collected using a visual oddball paradigm. P300 components were detected using a threshold algorithm operating on the delta band (0-4 Hz). Using data from four subjects, collected over a 7 to 12 week period, it was observed that the P300 amplitude tended to decrease within a session, and also between successive sessions. However, this decrease did not affect the detection rate. The eye-movement removal algorithm was tested on simulated and actual data, and resulted in a significant increase in detection rate. PMID- 17281901 TI - Comparison of saccade-related EEG signal with saccade-related independent component. AB - We have been research saccade-related EEG signals in order to predict beginning of saccade by EEG signal. We have already detected saccade-related EEG signal by ensemble averaging and saccade-related independent components (ICs) by independent component analysis (ICA). However, features of saccade-related EEG signals and saccade-related ICs were not compared. In this paper, saccade-related EEG signals and saccade-related ICs were compared in the point of the latency between starting time of a saccade and time when a saccade-related EEG signal or an IC has maximum value and in the point of the peak scale where a saccade related EEG signal or an IC has maximum value. PMID- 17281902 TI - Salient EEG channel selection in brain computer interfaces by mutual information maximization. AB - Modern brain computer interface (BCI) applications use information obtained from the user's electroencephalogram (EEG) to estimate the mental states. Selecting an optimal subset of the EEG channels instead of using all of them is especially important for ambulatory EEG where the user is mobile due to reduced data communication and computational load requirements. In addition, elimination of irrelevant sensors improves the robustness of the classification system by reducing dimensionality. In this paper, we propose a filter approach for EEG channel selection using mutual information (MI) maximization. This method ranks the EEG channels, such that the MI between the selected sensors and class labels is maximized. This selection criterion is known to reduce classification error. We employ a computationally efficient approach for MI estimation and EEG channel ranking. This approach is illustrated on EEG data recorded from three subjects performing two mental tasks. Experiment results show that the proposed approach works well and the position of the selected channels using the proposed method is consistent with the expected cortical areas for the mental tasks. PMID- 17281904 TI - Vagal stimulation markedly suppresses arrhythmias in conscious rats with chronic heart failure after myocardial infarction. AB - Our previous study showed that chronic vagal stimulation (VS) prevented the cardiac remodeling and improved the prognosis of chronic heart failure (CHF) rats after large myocardial infraction (MI). Antiarrhythmic effects of VS were assumed to produce such a beneficial outcome. There-rhythmias. fore, we examined the effects of VS on cardiac ar- The ECG transmitter and a radio-controlled stimulator were implanted in the healed MI rat (n=8). The electrical stimulation of the right cervical vagus started at 3-5 months after MI and lasted for 7 days. ECG data were analyzed for counting the premature ventricular or supraventricular contraction (PVC, PSVC) and for the spectral analysis of heart rate variability. All the rats had a variety of ventricular arrhythmias and the number of PVC or PSVC progressively increased to 5-15% of the total beats. VS effectively suppressed the occurrence of PVCs in 1-2 days. The 24-hour counts of average PVC plus PSVS counts were significantly decreased after VS (793±291 vs. 291±289 counts/hr, p<0.05). The power of high-frequency (0.5-2.0 Hz) oscillations of R-R interval was significantly increased by the VS (1.26±0.47 vs. 3.73±0.74, p<0.01, before and 1 day after stop VS). These results showed that VS markedly suppresses arrhythmias in conscious CHF rats. The antiarrhythmogenic properties may partially account for the beneficial effect of VS on survival of CHF rats. PMID- 17281903 TI - Mechanism of Reentry Trigged by EADs in Long-QT Syndrome: A Simulation Study. AB - This simulation study is carried out in two-dimensional two-dimensional two dimensional tissue of Luo-Rudy model of mammalian ventri-cular ventri-cular ventri-cular myocytes. Mechanism of reentry trigged by early after depolarizations after-depolarizations after-depolarizations (EADs) in long-QT syndrome (LQTS) has been study in this paper. LQTS is simulated by reducing the membrane conductance of IKsfor LQT1 and IKrfor LQT2, and by altering the steady-state inactivation of the fast sodium current INafor LQT3. The endocardium is paced 10 times at a constant basic cycle length (BCL) of 500ms, and following a 2000ms pause, a S2 stimulus is applied. If shape, size and position of M cell domain is suitable, EADs with higher amplitude formation near the boundary between endocardial domain and M cell domain provide the trigger for reentrant excitation. Reentry once initiated is more likely to self-terminate self-terminate self-terminate in LQT1 tissue. In LQT2 tissue, functional reentry is maintained by the continuously generating of EADs in the mid of M cell domain. In LQT3 tissue, functional reentry is maintained for the reason that the conduction velocity of EAD induced reentrant wave is very slowly, and the tip of it is anchored at the mid of M cell domain. PMID- 17281905 TI - Intravascular parasympathetic cardiac nerve stimulation prevents ventricular arrhythmias during acute myocardial ischemia. AB - Although previous animal studies clearly demonstrated antiarrhythmic effects of vagal stimulation during acute myocardial ischemia, highly invasive nature of vagal stimulation limited its clinical use. Recently, intravascular parasympathetic cardiac nerve stimulation (IPS) has emerged as a novel approach to the cardiac autonomic nervous system. We hypothesized that IPS might prevent ventricular arrhythmias during acute myocardial ischemia. METHODS: The IPS (36 V, 10 Hz) was performed in superior vena cava using an expandable electrode-basket catheter. In 18 open-chest dogs, left anterior descending coronary artery ligation was performed without IPS (control group, n= 6), with IPS (IPS group, n= 6) and with IPS and right atrial pacing at 180/min (IPS+P group, n=6). The ECGs were monitored for 60 min. The incidence and severity of ventricular arrhythmias were analyzed. RESULTS: The IPS significantly decreased the frequency of premature ventricular contractions (control group: 9.1 ± 4.6/min, IPS group: 0.2 ± 0.4 /min, IPS+P group: 10.6 ± 4.2 / min; p<0.05). The frequency of ventricular tachycardia was lower in IPS group (0 ± 0 /min) than in control group (0.15 ± 0.18 /min, p<0.05) and than in IPS+P group (0.17 ± 0.12 /min, p<0.05). The incidence of ventricular fibrillation was lower in IPS group (0%) than in control group (33.3%) and than in IPS+P group (33.3%). CONCLUSIONS: The IPS suppressed ventricular arrhythmias during acute ischemia mainly through its bradycardiac effect. PMID- 17281906 TI - A New System for Whole-atrial Epicardial Mapping. AB - Epicardial mapping system is an important tool in the study and treatment of cardiac arrhythmias. Surgical therapy has been applied to eliminate atrial fibrillation (AF) for almost two decades, but there is still little effect on the treatment of AF in respect that the mechanism of AF is still unknown. Further investigation into the electrophysiological properties in AF is required to develop an appropriate treatment, though radiofrequency ablation has opened the new era of therapies for AF. Nevertheless, the sequential epicardial mapping for whole-atrium will increase the benefit to understand electrical mechanism during AF. The purpose of our research is to detect the electrical activity on the atrial surface and therefore find the optimal technique or ablation procedures to prevent AF. Animal tests were operated on ten dogs in which chronic AF had been induced. In experiment whole-atrial electrodes were located on the atrial surface after the heart had been exposed. Each 20-second sampling data during sinus or atrial fibrillation rhythm were recorded and stored for analysis. Three dimensional dynamic maps are presented clearly and the activity of sinus or AF rhythm can be seen quite differently. The active isopotential map can display the dynamic electrical conduction of the atria as a movie. This study demonstrates the flexibility of the system in AF research. PMID- 17281907 TI - QRST cancellation using bayesian estimation for the auricular fibrillation analysis. AB - The accurate extraction of the atrial fibrillation (AF) signal from the ECG is a challenging task. The performance of its frequency analysis is based on this accuracy. When the atrioventricular node modelling is addressed, the precision of the AF amplitude estimation plays an important role. In this work, we propose an AF estimator based on a bayesian approach. The a priori knowledge necessary to achieve good estimation performances is shown to be weak. The presented method is compared to classical ones such as the Average Beat Substraction (ABS) but also to modern one that is the Blind Source Separation (BSS) technic. The performances of the methods are illustrated on a small set of examples. The conclusion is that the proposed method gives an accurate global estimation of the AF signal but also locally since our results do not exhibit spurious oscillations at the time location of the R wave. PMID- 17281908 TI - Suitability of Genetic Algorithm Generated Models to Simulate Atrial Fibrillation and K+Channel Blockades. AB - Channel modifications resulting from atrial fibrillation (AF) have received a great deal of attention over the last decade. Mathematical models can be used to help understand the significance of these changes. These models can be used to predict the responses of specific channel-blocker drugs on normal action potentials (NAPs) and action potentials (APs) present during chronic AF (AFAP). Unfortunately, to date, models are "average representations" of APs, but AP morphology varies significantly through the atria. To account for this natural heterogeneity, which plays a very important role in determining the nature of AF, we previously presented a genetic algorithm (GA) to automatically fit the conductance parameters of atrial model APs based upon experimentally measured APs. In this study, three automatically produced models from different canines were used to investigate the suitability of this technique in assessing the effects of AF and drug-related channel modifications. PMID- 17281910 TI - Computer-assisted arthroplasty using bio-engineered autografts. AB - Recent advances in tissue-engineered cartilage open the door to new clinical treatments of joint lesions. Common to all therapies with in-vitro engineered autografts is the need for optimal fit of the construct, to allow screwless implantation and optimal integration into the live joint. Computer Assisted Surgery techniques are prime candidates to ensure the required accuracy while at the same time simplifying the procedure. A pilot study has been conducted aiming at assembling a new set of methods to support ankle joint arthroplasty using bio engineered autografts. Computer assistance allows planning of the implant shape on a CT image, manufacturing the construct according to the plan and interoperatively navigating the surgical tools for implantation. A rotational symmetric model of the joint surface was used to avoid segmentation of the CT image; a new software was developed to determine the joint axis and make the implant shape parameterisable. A complete cycle of treatment from planning to operation was conducted on a human cadaveric foot, thus proving the feasibility of computer-assisted arthroplasty using bio-engineered autografts. PMID- 17281909 TI - A simplified method for the calculation of equivalent squares of irregular photon fields. AB - It is showed that the empirical scatter-radius function (Day function) used to generate the equivalent-field tables is a good approximation to the results of normalized scatter-air ratios extracted from the British Journal of Radiology (BJR) beam data for depths up to 10 cm. Accuracy can be improved by making the Day function depend on depth. Equivalent squares, determined by sector integration of the original or modified Day functions, are suitable for megavoltage photon-beam dose calculations in irregular as well as rectangular fields. We make further simplification for the functions to calculate equivalent squares by no use of scatter dose data that is often difficult to get for hospitals. The simplified method has the same accuracy compared to the original or modified Day functions. PMID- 17281911 TI - Do we have the data to take informed decisions in Healthcare Technology Management (HTM) related issues? A Conceptual HTM-IS Framework. AB - This paper considers the data and information needs for a broad range of environments, focusing on information-poor environments that may be well resourced in other respects. A generic framework for the establishment of a comprehensive healthcare technology management information system (HTMIS) is suggested. PMID- 17281913 TI - Clinical engineering department strategic graphical dashboard to enhance maintenance planning and asset management. AB - The Clinical Engineering (a.k.a. Biomedical Engineering) Department has heretofore lagged in adoption of some of the leading-edge information system tools used in other industries. This present application is part of a DOD-funded SBIR grant to improve the overall management of medical technology, and describes the capabilities that Strategic Graphical Dashboards (SGDs) can afford. This SGD is built on top of an Oracle database, and uses custom-written graphic objects like gauges, fuel tanks, and Geographic Information System (GIS) maps to improve and accelerate decision making. PMID- 17281912 TI - Optimal Medical Equipment Maintenance Service Proposal Decision Support System combining Activity Based Costing (ABC) and the Analytic Hierarchy Process (AHP). AB - This study describes a framework to support the choice of the maintenance service (in-house or third party contract) for each category of medical equipment based on: a) the real medical equipment maintenance management system currently used by the biomedical engineering group of the public health system of the Universidade Estadual de Campinas located in Brazil to control the medical equipment maintenance service, b) the Activity Based Costing (ABC) method, and c) the Analytic Hierarchy Process (AHP) method. Results show the cost and performance related to each type of maintenance service. Decision-makers can use these results to evaluate possible strategies for the categories of equipment. PMID- 17281914 TI - The Novel Immunobiosensors for Detection of Escherichia coli O157:H7 Using Electrochemical Impedance Spectroscopy. AB - Immunobiosensors were developed for detection of Escherichia coli O157:H7 based on the surface immobilization of monoclone antibodies onto indium tin oxide (ITO) electrodes. The immobilization of antibodies onto ITO chips was carried out by silanization. The effects of epoxysilane monolayer, the antibody layer on the electrochemical properties of the electrode, and the combined target bacteria were analyzed through cyclic voltammetry and electrochemical impedance spectroscopy. By using Randles model as the equivalent circuit, the concentration of the target bacteria can be quantitatively analyzed in terms of the change of electron transfer resistance. The biosensor could detect the target bacteria with a detection limit of 4×103CFU/mL. A linear response was found between 4×103- 4×106CFU/mL. This biosensor was characterized with high sensitivity, excellent selectivity, short detection time and easy operation It has a promising application in clinical laboratory diagnoses, environmental detection and food safety. PMID- 17281915 TI - A new multi-site probe array with monolithically integrated parylene flexible cable for neural prostheses. AB - This work presents a new multi-site probe array applied with parylene technology, used for neural prostheses to record high-level cognitive neural signals. Instead of inorganic materials (e.g. silicon dioxide, silicon nitride), the electrodes and conduction traces on probes are insulated by parylene, which is a polymer material with high electrical resistivity, mechanical flexibility, biocompatibility and easy deposition process. As a result, the probes exhibit better electrical and mechanical properties. The all dry process is demonstrated to fabricate these probe arrays with monolithically integrated parylene flexible cables using double-side-polished (DSP) wafers. With the parylene flexible cables, the probes can be easily assembled to a high density 3-D array for chronic implantation. PMID- 17281916 TI - Post-hybridisation by Electrophoresis for Reinforcing the Hybridization Result. AB - In this paper, we developed an electrophoresis method for reinforcing hybridization efficiency, and distinguishing the perfectly matched sequences from the mismatched ones. The non-specific binding labeled targets in the hybridization were effectively removed by electrophoresis instead of the conventional washing procedure in the post-hybridisation process. During electrophoresis, the hybrids (the dual-spiral structures formed in hybridization) would be unchained when targets were continuously removed. In this case, not only the non-specific binding labeled targets, but also the targets participating in hybridization would be removed. Therefore, only the perfectly matched sequences had the distinct hybridization signals, the perfectly matched probes from the single-base mismatched ones could more easily be distinguished, and the single nucleotide polymorphisms (SNP) genotypes were also easily determined by dual color fluorescence targets. PMID- 17281917 TI - A Simple Method of Fabricating Weir-type Filters with Interdigital Aligned Full polymer Microfluidic Channels for Blood Cell Fractionation. AB - This paper describes a new method to fabricate large scale 3D weir-type filter for cell fractionation. The 3D structure is realized by a conformal bonding of two separate PDMS (poly-dimethyloxane) layers with in-situ microchannels which are formed by the conventional soft lithographic techniques. Moreover, the microfluidics channels on the two PDMS are set to cross to each other to increase weir numbers and flow throughput. The gap space of the weir filters depends on the thickness of the photoresist coated for the master formation, thereby it can be defined as required from submicron to hundreds micron scale. A white blood cells (WBCs) extraction experiments with the full polymer fabricated filters are conducted to validate the proposed method.. The experimental results show that the weir-type filter array can fractionate the WBCs well from blood samples. Due to its intrinsic advantages of rapid process, high throughput and low cost, the proposed method is very promising for being integrated into Micro Total analysis System (μTAS). PMID- 17281918 TI - Microstructures formed on a low fluorescent glass using glassy carbon molding. AB - We report a pattern generation method on galss using hot embossing technology. Microstructures were formed on Borofloat, a low fluorescent glass, using a glassy carbon mold. A cubic block in the size of 100 um x 100 um x 50 um is the basic testing pattern. This block was repeated on a mirror polished glassy carbon wafer with a space in the pitch of 30 um. The whole pattern area is in 15 mm x 15 mm square on this carbon mold. Both the glass wafer and the mold were heated to 655 °C and embossing was processed at 2 MPa under vacuum (0.07 Pa). The state was held for 20 min, and then the embossed piece was cooling down to 200 °C naturally in the vacuum chamber. The pattern on mold were transferred compensate to the glass. Each fabrication cycle is about 1.5 hours. This method shows great potential to fabricate bio-MEMS devices efficiently with a very low cost. The main target is to fabricate the devices for highly sensitive fluorescent detection applications, which is very difficult to be realized using plastic substrates, A multi-channel pattern (with 70 um line and 400 um space) has been generated on a 20 mm square glassy carbon using a laser machine. The pattern replicated on glass chips has been demonstrated. PMID- 17281919 TI - Progress in developing a composite tissue-engineered aortic valve. AB - This paper reviews the rationale for developing a tissue-engineered aortic valve by building up the complex microstructure from its basic components, and presents recent progress towards that goal. Over the past 4 years, we have been working on engineering the functional components of the composite valve the collagen fiber bundles, the elastin sheets, and the hyaluronan matrix that keeps the tissue hydrated. Most recently, we have been working on optimizing the geometry and material properties of the collagen constructs, by varying their size and aspect ratio, and the types of loading protocols the constructs experience during the culture process. PMID- 17281920 TI - Wireless Surgical Tools for Mechanical Measurements during Scoliosis Surgery. AB - Comprehensively understanding the mechanics of loads applied by orthopaedic surgeons and distributed to the spine during scoliosis corrective surgery may improve surgical outcome and patient safety. Instruments to measure forces applied by orthopaedic surgeons have been reported. This paper presents instrumented hooks and screws with a real time wireless data acquisition system to measure loads and moments distributed to the spine during scoliosis surgery. From laboratory tests, the maximum error of posterior/anterior forces and moments were 2-3% of the maximum loads during surgery. This study improves the understanding of mechanics during surgical correction. PMID- 17281921 TI - Micro-system Design for Wireless Endoscopy System. AB - This paper proposes a micro-system design for the wireless endoscopic capsule, which assures that the capsule has small size(less than 25mm*10mm), can implement the diagnoses of whole human digestive tract and provide real time endoscopic image monitoring. The designs of two core hardware parts inside the capsule, low power analog-digital mix-mode single-chip and micro-antenna are discussed in detail. A new automatic retransmission request (ARQ) communication scheme is proposed for the high quality image communication system. The micro antenna design with less than 9 mm diameter is implemented. The digital circuits have been verified on FPGAs and analog circuits have been simulated. The analog digital mix-mode single-chip has been implemented in 0.18μm CMOS process. PMID- 17281922 TI - IEEE 802.11 ECG monitoring system. AB - New wireless technologies make possible the implementation of high level integration wireless devices which allow the replacement of traditional large wired monitoring devices. This kind of devices favours at-home hospitalization, reducing the affluence to sanitary assistance centers to make routine controls. This fact causes a really favourable social impact, especially for elder people, rural-zone inhabitant, chronic patients and handicapped people. Furthermore, it offers new functionalities to physicians and will reduce the sanitary cost. Among these functionalities, biomedical signals can be sent to other devices (screen, PDA, PC...) or processing centers, without restricting the patients' mobility. The aim of this project is the development and implementation of a reduced size multi-channel electrocardiograph based on IEEE 802.11, which allows wireless monitoring of patients, and the insertion of the information into the TCP/IP Hospital network. PMID- 17281923 TI - Efficient linear algorithm for magnetic localization and orientation in capsule endoscopy. AB - To build a new wireless robotic capsule endoscope with external guidance for controllable GI tract examination, a sensing system is required for tracking the capsule's 3D location and 2D orientation. An appropriate sensing approach is to enclose a small permanent magnet in the capsule so as to establish a static magnetic field around. With the magnetic sensors outside the patient's body, some parameters related to this magnetic field can be detected, and the capsule's location and orientation can be calculated using an appropriate algorithm. In this paper, a linear algorithm is proposed to provide faster, more reliable computation, compared to the nonlinear algorithms. The results of simulation and real experiment show that satisfactory localization and orientation accuracy can be achieved using a sensor array with enough number of 3-axis sensors. PMID- 17281924 TI - Implantable Active Telemetry System using Microcoils. AB - The use of microcoils in an active telemetry system that is intended to be implanted in the body for biomonitoring applications is presented in this paper. To achieve a moderate transmission range, active telemetry was realized instead of passive telemetry by load modulation, which is often used in systems incorporating microcoils. Sample microcoils with a diameter of 1 cm and 16 windings were fabricated and used for tests. A telemetry system operating at the 27 MHz ISM band was constructed using a small number of circuit components. The performance of the constructed system was evaluated in a laboratory condition. The transmission range of the realized system was measured up to 20 cm when a biological tissue in a thickness of 1 cm was applied between the transmitter and the receiver. PMID- 17281925 TI - A ka-band low power Doppler radar system for remote detection of cardiopulmonary motion. AB - A low power Ka-band Doppler radar that can detect human heartbeat and respiration signals is demonstrated. This radar system achieves better than 80% detection accuracy at the distance of 2-m with 16-μW transmitted power. Indirect conversion receiver architecture is chosen to reduce the DC offset and 1/f noise that can degrade signal-to-noise ratio and detection accuracy. In addition, the radar has also demonstrated the capability of detecting acoustic signals. PMID- 17281926 TI - Multimodal affective user interface using wireless devices for emotion identification. AB - Emotion is a fundamental, essential, and critical function of human brain. It's desirable to create intelligent computer systems to make emotion identification accurate and reliable. Firstly, we discuss the importance of emotion research. Then, we report on our efforts in developing multimodal affective user interface system used in emotion identification. There are different modalities of synchronous inputs from the user using wireless sensors and multimedia computer sensing, including physiological signals, facial expressions, speech signals, and behavioral video stream. The physiological signals are collected using wireless sensors with Bluetooth technology. The images of facial expression and the ongoing videos of behavior and gesture are recorded by several cameras connected to different controlling computers. All these signals and experiments are collected synchronously in real time to make multimodal signal analysis convenient. Finally, we discuss usages of this system in emotion assessment, learning and training. PMID- 17281927 TI - Wireless Technology and System Integration in Body Area Networks for m-Health Applications. AB - m-Health integrates mobile computing, medical sensor, and communications technologies for mobile health-care applications. Wireless body area networks (WBANs) of intelligent sensors represent an emerging technology for system integration with great potentials for unobtrusive ambulatory health monitoring during extended periods of time. However, system designers will have to resolve a number of issues, such as severe limitations of sensor weight and size necessary to improve user's compliance, sensor resource constraints, intermittent availability of uplink connectivity, reliability of transmission, security, and interoperability of different platforms. We present current and emerging wireless technologies and developments in pervasive and mobile technologies that are vital for implementation of WBAN-based monitors and m-Health system integration. We emphasize the problem of reliable system operation with extremely low power consumption and discontinuous connectivity, which are typical for ambulatory monitoring. PMID- 17281928 TI - Wearable medical devices using textile and flexible technologies for ambulatory monitoring. AB - Health smart clothes are in contact with almost all the surface of the skin offer large possibilities for the location of sensors for non invasive measurements. Head band, collar, tee-shirt, socks, shoes, belts for chest, arm, wrist, legs ... provide localization with specific purpose taking into account their proximity of an organ or a source of biosignal, and also its ergonomic possibility (user friendly) to fix a sensor, and the associated instrumentations (batteries, amplifiers, signal processing, telecom, alarm, display ...). Progress in science and technology offers, for the first time, intelligence, speed, miniaturization, sophistication and new materials at low cost. In this new landscape, microtechnologies, information technologies and telecommunications are a key factor. Microsensors : Microtechnologies offer the possibility of small size, but also intelligent, active device, working with low energy, wireless and non invasive or mini invasive. These sensors have to be thin, flexible and compatible with textile, or made using textile technologies, new fibers with specific properties: mechanical, electrical, optical ... The field of applications is very large, e.g. continuous monitoring on elderly population, professional and military activities, athlete's performance and condition, and people with disabilities. The research are oriented toward two complementary directions: Improving the relevancy of each sensor and increasing the number of sensors for having a more global synthetic and robust information. PMID- 17281929 TI - Wearable accelerometer in clinical use. AB - To improve the equality of life, we must prevent the falls in both healthy elderly and patients with the cerebrovascular diseases. Wearable accelerometer was applied to monitor. In this paper, we introduced two different clinical applications. On is fall detector and the other is monitoring device for screening test. 1) We have developed body-worn accelerometer with data loggers and monitored the daily of life in patient with Parkinson disease. The patients wore the device and monitored falls while walking and standing. As a result, we could obtain fall times for a long period. 2) The ability of walking and standing have been evaluated by Timed up & go test. We used telemetry with accelerometer. The stability of walking could be evaluated by the acceleration signals. The simple body-won device can be useful for fall study. PMID- 17281930 TI - MagIC System: a New Textile-Based Wearable Device for Biological Signal Monitoring. Applicability in Daily Life and Clinical Setting. AB - The paper presents a new textile-based wearable system for the unobtrusive recording of cardiorespiratory and motion signals during spontaneous behavior along with the first results concerning the application of this device in daily life and in a clinical environment. The system, called MagIC (Maglietta Interattiva Computerizzata), is composed of a vest, including textile sensors for detecting ECG and respiratory activity, and a portable electronic board for motion detection, signal preprocessing and wireless data transmission to a remote monitoring station. The MagIC system has been tested in freely moving subjects at work, at home, while driving and cycling and in microgravity condition during a parabolic flight. Applicability of the system in cardiac in-patients is now under evaluation. Preliminary data derived from recordings performed on patients in bed and during physical exercise showed 1) good signal quality over most of the monitoring periods, 2) a correct identification of arrhythmic events, and 3) a correct estimation of the average beat-by-beat heart rate. These positive results supports further developments of the MagIC system, aimed at tuning this approach for a routine use in clinical practice and in daily life. PMID- 17281931 TI - 3D TRUS Image Segmentation in Prostate Brachytherapy. AB - Brachytherapy is a minimally invasive interventional surgery used to treat prostate cancer. It is composed of three steps: dose pre-planning, implantation of radioactive seeds, and dose post-planning. In these procedures, it is crucial to determine the positions of needles and seeds, measure the volume of the prostate gland. Three-dimensional transrectal ultrasound (TRUS) imaging has been demonstrated to be a useful technique to perform such tasks. Compared to CT, MRI or X-ray imaging, US image suffers from low contrast, image speckle and shadows, making it challenging for segmentation of needles, the prostates and seeds in the 3D TRUS images. In this paper, we reviewed 3D TRUS image segmentation methods used in prostate brachytherapy including the segmentations of the needles, the prostate, as well as the seeds. Furthermore, some experimental results with agar phantom, turkey and chicken phantom, as well as the patient data are reported. PMID- 17281932 TI - Local region based medical image segmentation using j-divergence measures. AB - In this paper, we propose a novel variational formulation. The originality of our formulation is on the use of J-divergence (symmetrized Kullback-Leibler divergence) for the dissimilarity measure between local and global regions. The intensity of a local region is assumed to follow Gaussian distribution. Thus, two features - mean and variance of the distribution of every voxel are introduced to ensure the robustness of the algorithm when noise appeared. Then, J-divergence is used to measure the "distance" between two distributions. The proposed method is verified on synthetic and real medical images. The experimental results are very encouraging for medical image segmentation. PMID- 17281933 TI - Segmentation Through Point-based Multiscale Deformable Model. AB - We propose a local weak form formulation for the geometric deformable model (GDM) which is capable of achieving robust segmentation results for noisy and broken edges. The local weak form partial differential equation (PDE) is solved on the analysis/evolution domain which is adaptively sampled by unstructured point cloud for improved accuracy and/or reduced computational cost. The fundamental power of this strategy rests with the explicit integration of neighboring information when constructing inter-point constraint and image-derived evolution force for each front point within a local influence domain adaptively determined by geometry and image information. As a result, this local weak form GDM naturally unifies the essences of the geometric and parametric snakes through automatic local scale selection at each contour point, and exhibits their respective fundamental strengths of allowing stable boundary detection when the edge information is weak and possibly discontinuous while maintaining the abilities to handle topological changes during front evolution. In particular, this paper presents an implementation of the method through local integration of the level set function and the evolution forces. Experimental results on synthetic and real images demonstrate its superior performance. PMID- 17281934 TI - Extension of deformable models: hybrid approaches for analysis of medical images. AB - Despite deformable models' wide applicability in medical image segmentation, they are sometimes not adequate by themselves to achieve a desired degree of automation, a guaranteed level of accuracy, or an outcome beyond segmentation. In such situations, other methods may be combined with a deformable model to extend its abilities, overcome its shortcomings or increase the assurance of the segmentation accuracy. As examples of such combinations, we discuss the use of deformable models in hybrid approaches, to obtain curvilinear models of tubular structures, patient specific models of the abdominal aortic vessel system, and tissue models for radiation simulation. PMID- 17281935 TI - Evaluation of Segmentation algorithms for Medical Imaging. AB - This paper describes an approach to be used for medical image segmentation evaluation. The process for segmenting organs and structures from medical images is gaining increased importance in the diagnosis of diseases and in guiding minimally invasive surgical and therapeutic procedures. While investigators are continuing to develop novel new segmentation approaches, little attention has been given to the development of a uniform and common framework for and performance metrics to be used in comparing different algorithms, in optimizing algorithms and in evaluating their performance. Choosing an appropriate effectiveness measure of object segmentation is a difficult task and weighting the importance of different possible performance metrics requires matching the metrics to the segmentation objectives. However, in all tasks, it is now believed that three types of metrics must be measured and reported: accuracy, precision and efficiency. In this paper, we review some of these metrics. PMID- 17281936 TI - Studies on New Schemes for ECG Forward Problem Simulations. AB - Quantificationally, from cardiac bioelectric process, working out body surface potential distributing, often called ECG Forward Problem, is an important aspect of electrocardiogram simulation. Here we explore some new schemes to carry it out, give a new method for modeling torso and ventricles, and propose an actual action potential model and myocardial excitation vector propagation algorithm. Results show that the new simulation model reaches the present level of electrocardiogram model; that it serves as a way to carry out electrocardiogram simulation. PMID- 17281937 TI - The ischemic heart: what causes ectopic beating? AB - The mechanisms by which spontaneous electrical activity originates in the ischemic heart and leads to arrhythmia remain unknown, however mechanical stretch of the diseased region has been hypothesized to play a role. The goal of this study is to investigate the conditions that favor the initiation of stretch induced premature beats in the ischemic heart. We employ a mathematical model of the ischemic cell subjected to stretch. The study found that upon stretch, spontaneous beats occur in the ischemic cell, which are due to the stretch induced re-activation of the L-type calcium current. PMID- 17281938 TI - Cardiac electromechanics and the forward/inverse problems of electrocardiology. AB - The mechanical motion of the heart plays a role in determining the waveforms observed in an ECG. This study is designed to ascertain, from a theoretical perspective, the influence of this motion. This is achieved through an analysis of a detailed forward model including a full bidomain description and a strongly coupled model of cardiac electromechanics. Simulations were run on identical problems with and without the inclusion of mechanical deformation and the results were analyzed with a view towards the inverse problem of electrocardiology. Initial results have shown the QRS complex to be largely invariant under deformation, but significant changes in T wave morphology have been observed. Further analysis has revealed that it is the effect of the cell-level mechanics on repolarization that is primarily responsible for these changes as opposed to the tissue deformation. PMID- 17281940 TI - A comparison of multilevel solvers for the cardiac bidomain equations. AB - Computing the extracellular potentials in a bidomain cardiac activation model is a computationally significant step in the solution process. Thus, using a fast solver can drastically reduce the overall time of simulation. Solving for the extracellular potentials involves inverting the matrix coming from the elliptic equation describing the extracellular-intracellular potential coupling. Elliptic equations are known to yield matrices that become progressively more ill conditioned as the spatial resolution is increased. However, optimal multilevel solution methods are known to exist for these equations given enough effort is placed into developing the correct solution components. Two multilevel solvers that automatically perform much of this work are black box multigrid (BOXMG) and algebraic multigrid (AMG). In this paper, we compare the performance of BOXMG and AMG as solvers for the elliptic component of the bidomain equations. Our investigation is with respect to simulations of reentry in two-dimensional cardiac tissue. PMID- 17281939 TI - Construction of patient specific geometries suitable for the inverse problem of electrocardiography. AB - The ability to accurately construct a geometric representation of the heart and torso is a critical component for electrocardiographic inverse algorithms. Typically geometric models have been constructed using data acquired from imaging modalities such as MRI and CT. We propose a system where the torso surface geometry is obtained using a laser scanning device and the heart geometry is obtained using three-dimensional ultrasound. PMID- 17281941 TI - Fibrillation complexity as a predictor of successful defibrillation. AB - A major focus of Implantable Cardioverter Defibrillator (ICD) research has been to reduce the defibrillation shock energy to prolong battery life and provide an enhanced quality of life for the patient. We investigated whether the degree of disorganization (complexity) of the electrogram is correlated with defibrillation shock outcome. The study data sets were recorded using the high voltage leads of an ICD during device implantation. A total 57 data segments from 19 patients were analyzed. Beat cycles were identified using a novel wavelet based method. Two algorithms were proposed and implemented to quantify the disorganization of the electrogram signals: Approximate Entropy and Cross Correlation. Entropy Index based on the ApEn method, was able to discriminate successful episodes from failure ones with a specificity of 93% and sensitivity of 100%. Similarity Index based on Cross correlation method, obtained a specificity of 72% and sensitivity of 66%. We conclude that the organization of a VF episode is related to the minimum energy required for successful defibrillation. PMID- 17281942 TI - Dose reponse behavior in a physiologically accurate defibrillation model. AB - Termination of an episode of ventricular fibrillation by electric countershock is a probabilistic phenomenon. In a clinical or experimental setting, defibrillation exhibits dose-response behavior. We demonstrate for the first time that a physiologically and anatomically accurate model of defibrillation is able to simulate this dose-response behavior. We also demonstrate the ability of this computational model to reproduce the full range of observed shock responses. Finally, we show that the brief cessation of electrical activity on the epicardial surface after a shock near the defibrillation threshold, the isoelectric window, can be explained by the slowed propagation velocity of transmural activation wavefronts around a filament of singularity in the myocardium. PMID- 17281943 TI - Cell and tissue responses to electric shocks invited paper. PMID- 17281944 TI - Diagnosis of biological tissue morphology and function with endoscopic optical coherence tomography. AB - We present some of the recent technological advances in our MEMS-based endoscopic optical coherence tomography (OCT) system for the enhancement of image fidelity and diagnosis. The endoscopic OCT system permits simultaneous cross-sectional OCT imaging and en face white-light visual guidance as well as fluorescence imaging guidance. The transverse and axial resolutions of the OCT scope are roughly 12μm and 10μm, respectively, and the axial resolution can be enhanced to 3um if connecting it to our recent custom sub-8fs Ti:Al2O3laser. To test the endoscopic OCT system for imaging diagnosis of early epithelial cancers, rat bladder cancer models were used and the results show over 90% sensitivity and specificity. Applications in imaging of bladder functions and engineering tissue growth are demonstrated. PMID- 17281945 TI - Optical Coherence Tomography: PFMC Model and Endoscopic Probe. AB - Optical Coherence Tomography (OCT) is a new technique mainly used in biomedical imaging. Here we present a Particle-Fixed Monte Carlo (PFMC) simulation for OCT. The scattering particles of the sample are assumed to be temporarily fixed randomly in the simulation process of backscattering light. The new model explains the exponential decay signal at the interface of different media layers in OCT experimental measurement. To extend the application area of OCT, an ultrasonic motor of 1mm in diameter is used to implement the circular imaging scanning in OCT endoscopic probe. PMID- 17281946 TI - Standard and line-field fourier domain optical coherence tomography. AB - Standard Fourier domain optical coherence tomography (FD-OCT) and line-field Fourier domain optical coherence tomography (LF-FDOCT) are described. The standard FD-OCT has the measurement speed of 36 frames/sec and one frame consisting 500 A-scans. The LF-FDOCT is an improved version of FD-OCT and determines a cross section of a sample without any mechanical scanning. The LF FDOCT has the measurement speed of 30 frames/sec, which is corresponding to 480 KH/ A-scan. A galvano-meter is introduced into the LF-FDOCT and it enables three dimensional OCT measurement with only one-dimensional mechanical scanning. PMID- 17281947 TI - Oral cancer diagnosis with optical coherence tomography. AB - We use an optical coherence tomography system with a specially designed probe to image the structures of tissues within the oral cavity for the diagnosis of oral precancer and cancer. Various types of oral mucosa, such as gingiva and buccal mucosa, normal and abnormal, can be well distinguished. PMID- 17281948 TI - Swept source based fourier domain functional optical coherence tomography. AB - Swept source based Fourier domain functional optical coherence tomography, which allows simultaneous imaging of tissue structure and physiology with high speed and high sensitivity, is described and demonstrated. PMID- 17281949 TI - From scans to sutures: computer-assisted orthopedic surgery in the twenty-first century. AB - Computer-assisted surgery is the process of using medical images, such as CT scans, X-ray fluoroscopy, or 3D ultrasound, to improve patient care. A typical surgical procedure begins by acquiring and processing a CT scan with specially developed image-analysis software. A surgeon then performs a "virtual surgery" on the patient to develop a preoperative plan. In the operating room the medical image is registered to the patient's anatomy by finding an optimal rigid-body transformation. This transformation allows an object or motion in one coordinate frame to be represented in the other frame, and thus a surgeon can visualize the location of an instrument deep within concealed anatomy while avoiding structures at risk. The operating surgeon can also use computer-tracked fluoroscopy or ultrasound for 3D guidance. For the past seven years, our interdisciplinary research group has been investigating fundamental problems in orthopedic surgery of bones and joints. This paper is an overview of the problems and solutions that have been tested in a set of pilot clinical trials in which we have treated more than 250 patients for early or advanced arthritis, poorly healed bone fractures, and treatment of deep bone tumors. PMID- 17281950 TI - Electrophysiology-guided deep brain neurosurgery. AB - Since the discovery of X-rays, medical imaging has played a major role in the guidance of surgical procedures. Recent advances in computer technology have only accelerated the rapid development of this field. As interventions become significantly less invasive, the use of pre-operative and intra-operative images to guide surgery has assumed increasing importance. Image-guided techniques have been employed for many years to plan and guide neurosurgical procedures. Amongst the most challenging areas of neurosurgery is the accurate targeting of nuclei within the deep brain for the treatment of Parkinson's and other motor system diseases. Unfortunately, standard CT and MR imaging does not permit the anatomical delineation of the targets, and so additional information, for example atlases and electrophysiological data, must also be employed. Both these forms of data can be mapped, using non rigid image registration techniques, to a standard representation of a brain acquired from MRI. The electrophysiology database can also evolve over time with the incorporation of data acquired from multiple patients operated in the past. Information of this nature can then be incorporated within the patient image, and serve as an invaluable tool in predicting to the surgeon the likely area of the target. This approach can significantly reduce the trauma associated with the insertion of multiple unnecessary electrodes to refine the target location, and speed up the procedure. PMID- 17281951 TI - Image registration: enabling technology for image guided surgery and therapy. AB - Imaging looks inside the patient's body, exposing the patient's anatomy beyond what is visible on the surface. Medical imaging has a very successful history for medical diagnosis. It also plays an increasingly important role as enabling technology for minimally invasive procedures. Interventional procedures (e.g. catheter based cardiac interventions) are traditionally supported by intra procedure imaging (X-ray fluoro, ultrasound). There is realtime feedback, but the images provide limited information. Surgical procedures are traditionally supported with pre-operative images (CT, MR). The image quality can be very good; however, the link between images and patient has been lost. For both cases, image registration can play an essential role -augmenting intra-op images with pre-op images, and mapping pre-op images to the patient's body. We will present examples of both approaches from an application oriented perspective, covering electrophysiology, radiation therapy, and neuro-surgery. Ultimately, as the boundaries between interventional radiology and surgery are becoming blurry, also the different methods for image guidance will merge. Image guidance will draw upon a combination of pre-op and intra-op imaging together with magnetic or optical tracking systems, and enable precise minimally invasive procedures. The information is registered into a common coordinate system, and allows advanced methods for visualization such as augmented reality or advanced methods for therapy delivery such as robotics. PMID- 17281952 TI - Computational models in image guided interventions. AB - In image-guided surgery and image-directed therapy a plan based on pre-procedure imaging is registered to the patient in the operating or treatment room using a 3D spatial localizer. The plan can be used as long as the transformation between plan and patient remains valid. Most systems use a rigid-body transformation restricting guidance to bony structures (e.g. orthopaedic surgery or maxillo facial surgery) or structures that are rigidly related to bone (e.g. neurosurgery). Fully 3D intra-operative imaging such as interventional MR allows image guidance to be extended to structures that move or deform during an intervention. However, this technology is expensive, interferes significantly with standard surgical protocols and requires computationally expensive non-rigid registration of the plan to the current patient scan. This talk will describe four examples where computational models of motion and anatomy are combined with 2D intra-operative imaging to extend the scope of image directed methods. In the first, image guided neurosurgery, we show how intra-operative imaging may account for distortion caused by the intervention itself. In two further applications - percutaneous ablation of metastatic liver disease and external beam radiotherapy of the lung - we show how computational models of motion might be used in conjunction with a therapy plan to guide the intervention. In the final example, selected from orthopaedic surgery, we show recent advances that demonstrate how a statistical shape model generated from example 3D images, can be used to provide image guidance without any pre-operative 3D imaging. PMID- 17281953 TI - Medical robotics and the operating room of the future. AB - Medical robotics is an evolving field with a relatively short history and limited market penetration, although some recent systems have shown some commercial success. Nevertheless, medical robotics shows great promise for improving patient care and may become a key component in the Operating Room of the Future (ORF), where high technology equipment will be integrated with medical imaging. This paper gives an overview of the medical robotics field and summarizes a recent ORF workshop in which participants concluded that standards are critical for an integrated approach. PMID- 17281954 TI - Magnetic images of pharmaceutical dosage forms in the human gastrointestinal tract. AB - Oral administration with solid dosage forms is a common route in the drug therapy widely used. The drug release by the disintegration process occurs in several gastrointestinal tract (GIT) regions. AC Biosusceptometry (ACB) was originally proposal to characterize the disintegration process of tablets in vitro and in the human stomach, through changes in magnetic signals. The aim of this work was to employ a multisensor ACB system to monitoring magnetic tablets and capsules in the human GIT and to obtain the magnetic images of the disintegration process. The ACB showed accuracy to quantify the gastric residence time, the intestinal transit time and the magnetic images allowed to visualize the disintegration of magnetic formulations in the GIT. The ACB is a non-invasive, radiation free technique, completely safe and harmless to the volunteers and had demonstrated potential to evaluate pharmaceutical dosage forms in the human gastrointestinal tract. PMID- 17281955 TI - Proportional microvolume capacitive liquid level sensor array. AB - A sensor array has been developed for use with laboratory automation to permit closed-loop control of liquid levels in a multiwell microplate geometry. We extended a simple electrical model for non-contact capacitance-based fluid sensors to describe a fluid-level dependency. The new model shows that a charge transfer based capacitance transducer, employing a liquid-specific calibration, can be used to obtain an output signal that varies linearly with the liquid level. The calibration also compensates for liquid-to-liquid conductivity and permittivity differences. A prototype 3×3 sensor array was built and tested using NaCl and ethanol solutions to simulate the range of conductivity and permittivity typical in biological and chemical research. Calibrated output signals were linear with liquid volume for all tested solutions (R2>0.92). Measurement error averaged 1.3 % (2.0 μl) with a standard deviation of 6.0% (9.0 μl). These results demonstrate the feasibility of developing a microvolume sensor array in essentially any M×N microplate geometry. PMID- 17281956 TI - A wavelet multiscale based method to separate the high and low frequency components of mechanomyographic signals. AB - The study of mechanomyographic (MMG) signals during dynamic contraction requires a criterion to select the cut-off frequency of the filter utilized to separate the low frequency (L.F) component (basically due to gross movement of the muscle or of the body) and the high frequency (HF) component (related with the vibration of the muscle fibers during contraction). To date, there is not an established criterion to carry out this selection. In this study, we propose a wavelet multiscale based method to aid to select a suitable cut-off frequency to separate correctly the LF and HF components. This method has been tested in an animal model, with the signal acquired during spontaneous ventilations with a capacitive accelerometer applied on the costal wall. This signal, as the MMG signals during dynamic contractions, has a LF component that is related with the movement of the thoracic cage, and a HF component that could be related with the vibration of diaphragm muscle fibers during contraction. The results obtained in the two respiratory tests analyzed indicate that cut-off frequencies around 10 and 3 Hz, respectively, must be employed to eliminate the LF component. The proposed wavelet multiscale method appears to be suitable to carry out a preliminary study of the MMG frequency content in dynamic contraction protocols. PMID- 17281957 TI - Use of a Light Emitting Diode (LED) Array for Bilirubin Phototransformation. PMID- 17281958 TI - A CMOS optical/potential image sensor with 7.5μm pixel size for on-chip neural and DNA spot sensing. AB - An optical/potential CMOS image sensor was designed and fabricated for bioimaging applications. The image sensor is capable to simultaneously sense an optical image and an on-chip potential image. Target applications of the sensor are on chip (optical + potential) neural imaging and on-chip DNA microarray sensing. The sensor has a QCIF (176 × 144) pixel array with alternatively aligned optical/potential sensing pixels. The pixel size is 7.5 μm × 7.5 μm. The potential resolution is confirmed to be better than 10 mV. An on chip fluorescence imaging of a mouse's hippocampus was performed to demonstrate that fluorescence imaging is possible with on-chip configuration. PMID- 17281959 TI - Development of the triple ring body surface laplacian sensor and its experimental study. AB - The Laplacian of the body surface potentials (Laplacian ECG--LECG) is a new approach to resolve spatially distributed bioelectric sources. LECG is a weak signal so an LECG sensor needs a good signal-to-noise ratio (SNR) and high common mode rejection ratio (CMRR). In this paper, we discuss a LECG sensor, which integrated tripolar concentric ring electrodes and signal conditioning circuit on a printed circuit board. The experimental results are in agreement with the theoretical calculations suggesting the feasibility of measuring the surface Laplacian. This lays the foundation for using such a device to assist in heart disease diagnoses. PMID- 17281960 TI - A linear epileptic seizure predictor based on slow waves of scalp EEGs. AB - Seizure prediction could change treatment of epilepsy, which has attracted substantial attention over the past two decades. Nonlinear EEG analysis techniques have made some successes at it, but linear analysis techniques being with the controversial results. We put forward a linear seizure predictor, which tracks the time evolution of the slow wave energy bigger than some preset threshold from scalp EEGs. The results from four generalized epileptic patients demonstrate that pre-seizure transition phases of several minutes can be identified clearly by our linear predictor, which could help us to a deeper understanding of the mechanism of seizure and open the possibility of clinical applications. PMID- 17281961 TI - Adaptive Threshold for QRS Complex Detection Based on Wavelet Transform. AB - This paper presents a novel approach, adaptive threshold algorithm, for QRS complex detection. It is based on two-to-four scales in COIFLET wavelet transform. Two initial thresholds are defined as up-limited-threshold (ULT) and down-limited-threshold (DLT) at the beginning of the detection. The system then automatically adjusts the values of the threshold to achieve optimal QRS detection. Simulation work shows that adaptive threshold algorithm can give more accurate results than fixed algorithms. By means of weights of missing and fault detection, ULT and DLT are adapted to get more accurate detecting results. More important for this algorithm is that it can increase the recognition efficiency greatly. PMID- 17281962 TI - Instantaneous frequency estimate of nonstationary phonocardiograph signals using hilbert spectrum. AB - A method for analyzing the nonlinear and non-stationary processes and investigating the instantaneous frequency of the practical medical signals is presented. The aim of this contribution is to explore the role that both empirical mode decomposition and Hilbert transform can be applied to play in phonocardiograph (PCG) signals. Hilbert transform is used to each intrinsic mode function to obtain the global time-frequency distribution of the underlying signal with a point of view of instantaneous frequency. Two kinds of clinical phonocardiograph signals with normal and abnormal cardiac functions were analyzed by using the proposed approach. The instantaneous frequency distributions of the PCG signals were also compared with the results by using the Morlet wavelet transform. Both simulation and experimental results were presented and discussed to demonstrate the power and effectiveness of the proposed approach. PMID- 17281963 TI - An novel clutter rejection filters applied to wideband blood flow velocity estimation. AB - Color flow imaging plays a major role in the diagnosis of many vascular diseases, especially cardiovascular disease. The imaging quality is highly influenced by the clutter originating from the vascular wall, stationary and slowly moving tissues and relative motion between the probe held by doctor and the blood flow. The clutter rejection filter in front of the mean frequency estimator will restrict the mean frequency estimation range because the power of the signal component induced by slowly moving blood is suppressed as well. Therefore, a novel scheme, using parameter estimation methods based on the two-dimensional correlation function model (2DCM) and the conventional down mixing, is proposed to clutter rejection. With the parameter estimation methods based on the 2DCM, both the center frequency and the mean Doppler frequency are estimated. The two dimensional information in range gate has been also sufficiently used. Simulation results have shown that this adaptive scheme has achieved superior performance in wideband blood flow velocity estimation. PMID- 17281964 TI - Multiple windows for estimation of locally stationary transients in the electroencephalogram. AB - In this paper, multiple windows, optimal for locally stationary processes (MW LSP) are used to estimate the spectrogram of the ElectroEncephaloGram (EEG) where we focus on the ability to estimate transient frequency changes. A peak of known frequency was evoked in the EEG spectrum in a predetermined time interval, by using a 9 Hz flickering light. We investigate the multiple windows corresponding to the mean squared error optimal time-frequency kernel for estimation of the Wigner-Ville spectrum. The kernel is optimal for a certain locally stationary process where the covariance function is determined by two one-dimensional Gaussian functions. PMID- 17281965 TI - Analysis on Spectral Properties of Projection Signals in 3D Tomography. AB - In this paper a new approach is presented to analyze the spectral behavior of the 3D projection signal generated via plane integrals. More accurate determination of the effective support region of the projection spectrum without approximation is realized compared to previous approaches. On the basis of acquired results, a more accurate and optimal interlaced sampling pattern is correspondingly established. Compared to the traditional progressive sampling method, a reduction of sampling points by the factor 4 is achieved. PMID- 17281967 TI - The response of the cross-bridge cycle model to oscillations in intracellular calcium: A mathematical analysis. AB - The response of smooth muscle cells to changes in blood pressure is a large component of the processes that regulate blood flow. Models of the mechanical behaviour of smooth muscle cells normally assume that the mechanical properties of the cell are dependent upon the state of attached myosin, this being determined by a four state kinetic model. An analysis of the behaviour of this kinetic model is presented here, in particular the response to oscillations in intracellular calcium. It is shown that the amplitudes of oscillation of the states in the kinetic model drop off rapidly with frequency and that at 1 Hz are of negligible magnitude. This is found to be true for a number of different combinations of model parameters, indicating that at the cardiac driving frequency the smooth muscle cell response is solely determined by the mechanical behaviour of the cells, without any influence of the biochemical processes, i.e. the response is purely passive. PMID- 17281966 TI - Cellular level electromechanical modeling and simulation of heart failure. AB - Effects of heart failure on the mechanical function of the heart are difficult to assess experimentally, yet they pose a serious physiological challenge. By integrating modified cellular action potential model based on experimental data of heart failure with modified Hunter-McCulloch-ter Keurs (HMT) mechanical heart cell model, an electromechanical cardiac cell model was constructed and used to study cellular mechanical properties of both fast and slow contracting myocytes in heart failure. The simulation results show that the differences of the electrical responses between failing cells and normal cells can cause slowing relaxation of the Ca2+ transient, and the difference of the Ca2+-TnC concentrations between fast and slow myocytes in failing hearts is much reduced than in nonfailing hearts. It results in a decrease of force, which might diminish the role of mechanoelectric feedback (MEF), then induce an increase of transmural action potential duration (APD) gradients. It might cause arrhythmia in heart failure. These results are in good accordance with experimental findings reported in the literatures and might motivate further research on modeling and simulation of heart failure at the tissue and the whole organ levels. PMID- 17281968 TI - Analysis of QT Interval Prolongation With Heart Failure by Simulation of Repolarization Process. AB - It has been postulated that action potential duration (APD) is prolonged and IKs, a slow component of delayed rectifier potassium current, decreases in heart failure. We have reported that QT interval is prolonged and expression weight of KCNE1, coding IKschannel, increases in patients with heart failure. Since it is known that increase in KCNE1 increases the maximum conductance of IKschannel, the mechanism of APD prolongation is not explained by over expression of KCNE1. In this study, we construct a cardiac membrane action potential simulation model based on the experimental data from Xenopus oocytes expressed KCNQ1 and KCNE1 to investigate the relationship between increase in KCNE1 and APD. In addition, we investigated effect of reduction in Ca2+-independent transient outward potassium current (Ito) on APD in heart failure. In simulation, APD at 5ng KCNE1 was 180.96ms, which was 4.63% longer than that at 1ng KCNE1 (APD=172.96ms) and 55.9% longer than that at 0.2ng KCNE1 (APD=110.96ms. In the cases of KCNQ1 alone and 0.2ng KCNE1 coinjected, APD shortened as density of Itodecreased, and APD prolonged as density of Itodecreased in other cases. This study shows that increase in KCNE1 expression level makes maximum conductance of IKschannel increase and IKschannel open slowly and conductance of IKschannel decrease according to the APD time scale. Therefore increasing the KCNE1 expression level may prolong APD with this mechanism. This method of constructing a simulation model based on experiments helps to explain the relationship between potassium currents and QT interval prolongation. PMID- 17281969 TI - Effects of 1800 MHz GSM Radiation on Human Monocytes and Trombocytes Membrane Anisotropy. AB - The purpose of our experiments was to measure the effects of 1800 MHz microwave radiation on membrane anisotropy of a human blood monocitar and trombocitar cell population. Power level of the applied CW microwave radiation was low enough to consider it to be athermal. Experience demonstrates that the natural tendency to decrease of cell membrane anisotropy is favourised by microwave irradiation. This tendency maintains after the ceasing of microwave irradiation. PMID- 17281970 TI - Mitochondrial permeability transition dynamics: an indicator of mitochondrial potassium channel opener. AB - Mitochondrial permeability transition (MPT) is an intracellular event that is closely related to apoptosis and necrosis. However, whether this process underlies the recently reported neuroprotective potency of mitochondrial potassium channel openers applied in vivo remains uncertain. This study aims to clarify this issue by determining the effects of potassium channel openers on MPT dynamics in vitro along with their in vivo effects. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min, followed by reperfusion. 30μl of diazoxide, an opener of the mitochondrial adenosine triphosphate-sensitive K+channel (mitoKATP), or NS1619, an opener of the mitochondrial Ca2+-activated potassium channel (mitoKCa) (2 mM and 0.1 mM respectively), was infused into the right lateral cerebral ventricle 15 min before the induction of ischemia. Neurological scores were assessed 24 h after MCAO and then infarct area was determined by standard 2,3,5-triphenyltetrazolium chloride staining techniques. To further clarify the capacity of diazoxide and NS1619 to protect mitochondria from Ca2+-induced MPT, we isolated brain-derived non-synaptosomal mitochondria and evaluated the effects of diazoxide and NS1619 on Ca2+ induced MPT dynamics through measurement of spectrophotometric alterations in light scattering at 520 nm. Neurological scores and infarct size were improved in animals pretreated with diazoxide and NS1619. In isolated mitochondria, MPT was readily induced by 200 μM Ca2+and was effectively inhibited by diazoxide and NS1619. The specific MPT pore opener atractyloside abolished the inhibitory effects. According to time-constant analysis, MPT dynamics was in accordance with the neuroprotective effects of channel openers in vivo. PMID- 17281971 TI - Modeling the diffusion of nitric oxide produced by neuronal cells in brain ischemia. AB - Mathematical models of NO diffusion were established to investigate the role of nitric oxide produced by neuronal cells in brain ischemia. Results showed that NO synthesized at early stage of brain ischemia could diffuse to a far more distant than that of a resting state. We speculate the roles of NO produced by neuronal cells in brain ischemia might have two different effects, depending on its concentration. PMID- 17281972 TI - Neural Probes for Concurrent Detection of Neurochemical and Electrophysiological Signals in vivo. AB - Electrochemical sensing with microelectrode arrays provides a means for monitoring neurotransmitter dynamics across multiple locations within a micro scale region of brain tissue. Here we present a multi-modal neural probe design for concurrent recording of neurochemical and electrophysiological signals in vivo. Prior to implantation, platinum sites on each array underwent platinum black electroplating and Nafion electropolymerization, which increased sensitivity to dopamine by 74% and decreased sensitivity to common interferents by at least 89%. In a series of three rats, we applied various electrochemical waveforms to platinum sites and monitored neural activity on adjacent iridium sites. We found that chronoamperometry and constant-potential amperometry did not alter firing rates at +0.25, +0.50, and +0.75 V. In addition, we have demonstrated multi-modal recordings of striatal neurons in response to medial forebrain bundle stimulation. PMID- 17281973 TI - Wireless multichannel integrated potentiostat for distributed neurotransmitter sensing. AB - Sensing neurotransmitters is critical in studying neural pathways and neurological disorders. An integrated device is presented which incorporates a potentiostat and a power harvesting and telemetry module. The potentiostat features 16 channels with multiple scales from microamperes to picoamperes. The wireless module is able to harvest power through inductively coupled coils and uses the same link to transmit data to and from the potentiostat. An integrated prototype is fabricated in CMOS technology, and experimentally characterized. Test results show RF powering introduces noise levels of 0.42% and 0.18% on potentiostat current scales of 500pA and 4nA respectively. Real-time multi channel acquisition of dopamine concentration in vitro is performed with carbon fiber sensors. PMID- 17281975 TI - Technical Details of the Implantable Myoelectric Sensor (IMES) System for Multifunction Prosthesis Control. AB - The limitation of current prostheses is not the devices themselves but rather the lack of sufficient independent control sources. A system capable of reading intra muscular EMG signals would greatly increase the number control sources available for prosthesis control. We are developing a multichannel/multifunction prosthetic hand/arm controller system capable of receiving and processing signals from up to sixteen implanted bipolar differential electromyographic (EMG) electrodes. An external prosthesis controller will decipher user intent from telemetry sent over a transcutaneous magnetic link by the implanted electrodes. The same link will provide power for the implanted electrodes. This paper describes some of the technical aspects of the implant and telemetry design. PMID- 17281974 TI - Monitoring Insertion Force and Electrode Impedance during Implantation of Microwire Electrodes. AB - the electrical impedance and the insertion force were monitored during the implantation of the microwire electrodes. The data reveals distinct phases in the force and impedance profiles corresponding to the different mediums the electrodes pass through. The impedance is shown to be linearly related to the pressure exerted by the electrode on the dura (p < 0.05, R2>0.8). While both insertion force and the impedance could be used to determine when the electrode touches and breaks through the brain surface, the later, especially the phase angle of the impedance, is shown to be more consistent and sensitive. It is proposed that the electrode impedance be used to provide more objective and accurate estimation of 1) when the electrode touches the brain; 2) the load distribution among the wires of the microwire array, and 3) the mechanical and immunological interactions between the electrode and the tissue in-vivo. The method can potentially improve the accuracy of electrode placement, and enable the development of better surgical procedures and apparatus. The principle could also be applied to other situations, such as endoscopic and minimum invasive surgeries. PMID- 17281976 TI - Development of a Microscale Implantable Neural Interface (MINI) Probe System. AB - Cortical recording devices hold promise for providing augmented control of neuroprostheses and brain-computer interfaces in patients with severe loss of motor function due to injury or disease. This paper reports on the preliminary in vitro and in vivo results of our microscale implantable neural interface (MINI) probe system. The MINI is designed to use proven components and materials with a modular structure to facilitate ongoing improvements as new technologies become available. This device takes advantage of existing, well-characterized Michigan probe technologies and combines them to form a multichannel, multiprobe cortical assembly. To date, rat, rabbit, and non-human primate models have been implanted to test surgical techniques and in vivo functionality of the MINI. Results demonstrate the ability to form a contained hydrostatic environment surrounding the implanted probes for extended periods and the ability of this device to record electrophysiological signals with high SNRs. This is the first step in the realization of a cortically-controlled neuroprosthesis designed for human applications. PMID- 17281977 TI - The analysis of electrode-recording-horizon in multi-electrode array(MEA). AB - There is a problem that can't be ignored in the MEA collected-signal-sorting process: When a neuron positions in two adjacent microelectrodes, can its activity be detected at the same time by both microelectrodes? Under certain conditions, the contact between the electrode and the cultured cell could be simplified as capacitive contact. Because the distance and the covering area affect the capacitance the amplitude of potential decreases rapidly with the increase of distance to the microelectrode. We show that common MEA chip whose spacing of electrodes is 200 μ m can't detect the neuronal potential in its adjacent electrodes simultaneously. About 100-recorded experiments data in our lab confirm this conclusion. PMID- 17281978 TI - Textile sensing interfaces for cardiopulmonary signs monitoring. AB - A wearable system able to monitor cardiopulmonary vital signs is presented. The innovative technological core of the system is based on the use of a textile conformable sensing cloth, where conducting and piezoresistive materials are integrated in form of fibres and yarns, giving rise to fabric sensors, electrodes and connections. Electrocardiogram and impedance pneumography signals are acquired through the same textile electrodes, while to discriminate between abdominal and thoracic activity, two piezoresistive fabric sensors are placed below the lower end of the sternum and at the level of the navel for recording the thorax and the abdominal pattern of breathing. The use of impedance pneumography methodology reduces the artefacts due to the movement, phonation and rib cage expansions disjointed from respiratory mechanics. All the signals are acquired simultaneously allowing a comparative control of the cardiopulmonary activity and artefacts rejection. PMID- 17281980 TI - A Low Power Linear Phase Digital FIR Filter for Wearable ECG Devices. AB - In this paper we present a low power linear phase digital FIR filter which is a part of an ECG-on-Chip. The ECG-on-Chip can be embedded into clothing to acquire the electrocardiogram (ECG) signal and send a warning message to a mobile phone or PDA if an abnormal ECG is detected. The proposed new filter structure significantly reduces the arithmetic operations for each sample which in turn lowers the power consumption. The filter is developed based on the interpolated finite impulse filter technique and is very attractive for a low cost and low power VLSI implementation. PMID- 17281979 TI - Sleep analysis for wearable devices applying autoregressive parametric models. AB - We applied time-variant and time-invariant parametric models in both healthy subjects and patients with sleep disorder recordings in order to assess the skills of those approaches to sleep disorders diagnosis in wearable devices. The recordings present the Obstructive Sleep Apnea (OSA) pathology which is characterized by fluctuations in the heart rate, bradycardia in apneonic phase and tachycardia at the recovery of ventilation. Data come from a web database in www.physionet.org. During OSA the spectral indexes obtained by time-variant lattice filters presented oscillations that correspond to the changes brady tachycardia of the RR intervals and greater values than healthy ones. Multivariate autoregressive models showed an increment in very low frequency component (PVLF) at each apneic event. Also a rise in high frequency component (PHF) occurred over the breathing restore in the spectrum of both quadratic coherence and cross-spectrum in OSA. These autoregressive parametric approaches could help in the diagnosis of Sleep Disorder inside of the wearable devices. PMID- 17281981 TI - WHAM: A novel, wearable heart activity monitor based on Laplacian potential mapping. AB - In this paper, a novel, wearable cardiac monitor (hereafter called WHAM) is proposed which allows a continuous and real-time monitoring of user's cardiac conditions. The proposed device is composed of 3 main components: a disposable electrode, a controller, and personal gateway (e.g., cellular phone, PDA, and smart phone etc.). The ECG signal is recorded according to the surface Laplacian of the body surface potential. We investigated the feasibility of WHAM as a wearable ambulatory device for continuously and on-line monitoring a user's cardiac conditions. To this end, the ECG signals recorded with WHAM were compared with those obtained by Wilson's unipolar chest leads, that is, v1 to v6. As a result, the ECG signals recorded with WHAM showed the similar morphology to Wilson's unipolar chest leads (v1 to v6) with the exception of P and T waves, although there is a difference between amplitudes of both signals. Also, it is shown that the R-peaks are accurately detected by the algorithm at the accuracy of more than 99% for the ECG signals of WHAM recorded during resting and walking. From these results, it is found that the WHAM shows enough feasibility and has advantages as a wearable ambulatory monitoring device in that the hardware is miniaturized enough small to integrate on a small region, thereby no wire leads need. PMID- 17281982 TI - A Study on a LVAD of a Wear-free Heart Pump. AB - This paper deals with hydrodynamic elements in a left ventricular assist device (LVAD) of a Wear-free Heart Pump, a rigid rotor with translational and slop motion suspended in an active magnetic bearing (AMB) system. First, the modeling of the dynamic behaviour of the rotor is pointed out. Then, the control strategy is developed. It is based on a suggested control method considering with the coupling effect from both ends of the rotor. The controller is executed on a DSP board. Simulation results and experiment results show the efficiency of the control strategy and validates the method applied to the pump. PMID- 17281983 TI - Heart rate variability monitoring and assessment system on chip. AB - This paper describes a system on a chip for heart rate variability monitoring and assessment. The system design applies digital techniques to measure RR intervals from ECG signals, then categorizes and stores HRV measures in an internal memory. The system has been tested for functionality, synthesized and laid out in a 0.5 μm CMOS technology in a 3x3 mm2chip with less than 1.5 μW power dissipation. The chip detects all R peaks with millisecond accuracy after the initial 2 seconds of data, and stores up to 2 minutes of continuous ECG data and up to 4 minutes of HRV histogram. Compact size, low cost, and low power consumption make this chip suitable for employment in modern implantable and portable devices. PMID- 17281984 TI - Progress towards a high-resolution retinal prosthesis. AB - Simulations of artificial vision suggest that 1000 electrodes may be required to restore vision to individuals with diseases of the outer retina. In order to achieve such an implant, new technology is needed, since the state-of-the-art implantable neural stimulator has at most 22 contacts with neural tissue. Considerable progress has been made towards that goal with the development of image processing, microelectronics, and polymer based electrodes and interconnects. An image processing system has been realized that is capable of real-time implementation of image decimation and filtering (for example, edge detection). Application specific integrated circuits (ASICs) have been designed and tested to demonstrate closed loop power control and efficient microstimulation. A novel packaging process has been developed that is capable of simultaneously forming a receiver coil, interconnects, and stimulating electrodes. PMID- 17281985 TI - Intracortical visual prosthesis research - approach and progress. AB - Following the early work of Brindley in the late 1960's, the NIH began intramural and extramural funding for stimulation of the primary visual coretex using fine wire electrodes that are inserted into area VI for the prupose of restoring vision in individuals with blindness. More recently researchers with experience in this projectbecame part of our multi-institutional team with the intention to identify and close technological gaps so that the intracortical approach might be tested in humans on a chronic basis. Our team has formulated an approach for testing a prototype system in a human volunteer. Here, we describe our progress and expectations. PMID- 17281987 TI - An Automatic Monitor System for AIROF Microelectrodes. AB - We present the design of an automatic electrode monitoring system for activated iridium oxide (AIROF) microelectrodes. It's a valuable piece of instrument in use in our laboratory to monitor the "health" of chronic implanted microelectrodes before neural stimulation or recording experiments. It is capable of automatically measuring electrode voltage and current of a large number of electrodes within minutes. It helped us identify some electrode degradation problems, which otherwise remained undetected would jeopardize the validity of neuroscience experiments that use these electrodes. So we strongly advocate the safe use of chronic microelectrodes by driving them within the water window and regularly monitoring their "health". PMID- 17281986 TI - Electrical stimulation to restore vestibular function development of a 3-d vestibular prosthesis. AB - Patients who fail to compensate for bilateral loss of vestibular sensory function are disabled by disequilibrium and illusory movement of the visual field during head movement. An implantable prosthesis that restores vestibular sensation could significantly improve quality of life for these patients. To be effective, such a device should encode head rotation in all 3 dimensions. We describe the 3 dimensional angular vestibulo-ocular reflex of normal chinchillas and vestibular deficient chinchillas undergoing functional electrical stimulation of the vestibular nerve. We also describe the design and fabrication of a head-mounted, 8 electrode vestibular prosthesis that encodes head movement in 3 dimensions. PMID- 17281988 TI - Biomimetic posture sensing and feedback for proprioception. AB - Kinesthesia is a sense of body posture and motion that arises from the interactions among the musculoskeletal system, a rich set of biological proprioceptors and the sensorimotor nervous system that mediates between them. This paper describes implantable sensor modalities to replace normal proprioceptors in feedback control. They can be packaged into miniature, wireless neural stimulators called BIONs. Their digitized signals can be transmitted efficiently to the external control system, which must then mediate between the sensing and stimulation functions in the available set of implants. This interaction will be perceived by the user of the prosthesis through residual sensory modalities such as proprioceptors in muscles and joints still under voluntary control and direct vision, as well as by a sense of effort in issuing commands to the prosthesis. These rich sources of information may be expected to induce a sense of kinesthesia similar that associated with manipulation of mechanically active tools and prosthetic limbs, perhaps obviating the need for more direct presentations of sensory data to the central nervous system. PMID- 17281989 TI - An image-based approach to measure the ferric ion diffusion coefficient in fricke gel dosimetry. AB - A numerical method was adopted to solve the diffusion equation to determine ferric ion diffusion coefficient in Fricke-agarose gels. A fast MR acquisition technique was employed to avoid smearing of acquired data due to diffusion over an extended time period. Our results show that for a Fricke gel contained 1 mM ammonium ferrous sulfate, 1% agarose, 1 mM sodium chloride and 50 mM sulfuric acid, its ferric ion diffusion coefficient is 1.73 10 2cm2h-1in room temperature. This value is consistent with the 1 ~ 2 10-2cm2h-1range obtained by previous studies under varying concentrations of gel ingredients. PMID- 17281990 TI - High-resolution dynamic imaging of contrast agent uptake in a beating heart. AB - Dynamic contrast-enhanced (DCE) MR cardiac imaging has been recognized as a unique and powerful tool for assessing both cardiac functions and physiological conditions of the heart tissues (e.g., tissue rejection following heart transplantation). However, because of cardiac motion and the limited data acquisition speed of existing MRI techniques, it has been very difficult to acquire dynamic images of very high spatiotemporal resolution. This paper proposes a new generalized series (GS) based imaging technique to overcome this challenging problem. Specifically, the proposed technique collects two data sets: a) a sequence of highresolution reference images over several cardiac cycles using a gated cine acquisition scheme before the injection of a contrast agent (or a molecular probe), and b) a sequence of reduced data sets with very high frame rate during the transient wash-in/wash-out stage of the contrast agent. A GS model is then used to combine these two data sets to reconstruct a high resolution image sequence, capturing both the cardiac motions and dynamic signal changes due to the interaction of the contrast agent with the cardiac tissues. The proposed technique has been validated using both simulated and experimental data, which show that high-resolution dynamic images can be acquired with as few as 8 encodings (in contrast to 256 encodings required in the traditional Fourier transform-based methods). The technique provides a very effective tool for physiological imaging of the beating heart with molecular probes. PMID- 17281991 TI - Adaptive K-space Updating Methods for Dynamic MRI Sequence Estimation. AB - In dynamic Magnetic Resonance Imaging (MRI), due to the limitation of imaging speed, it is commonly required to reconstruct the images from a reduced fourier encoded K-space sequence. This paper presents two temporal model based methods to estimate the un-acquired K-space data, called Adaptive K-space Updating (AKU) methods. The AKU reconstruction algorithms are directly applicable to the truncated K-space sequence generated by the well known Fourier Keyhole (FK) encoding scheme. The experimental study on the real MRI data shows that the proposed AKU methods can produce images with much lower reconstruction error than conventional FK method. PMID- 17281992 TI - Comparison of Motion Encoding Waveforms for Magnetic Resonance Elastography at 3T. AB - Magnetic resonance (MR) elastography has the ability to combine the inherent soft tissue contrast of traditional MR imaging with quantitative maps of tissue stiffness. Mechanical properties of tissues can vary greatly with disease and degeneration, and can illuminate structure-function understanding of tissues. Dynamic MR elastography is a phase contrast-based method for imaging the transmission of strain waves in an object. The present study evaluates the theoretical and empirical results of using trapezoidal and sinusoidal motion encoding gradients (MEGs) for the purposes of elastography at 3T. The study evaluated the phase-to-noise ratio for the methods, and found excellent agreement between the theoretical predictions and experimental results. The sinusoidal MEGs were predicted to have a relative PNR decrease of 21.5%, which compares very well with the experimental PNR decrease of 19.1% (95% CI = 17.1% to 21.0%). These results show the trapezoidal MEGs provide more sensitivity to strain wave transmission for the purposes of MR elastography. PMID- 17281993 TI - Using the Perceptual Difference Model (PDM) to Optimize GRAPPA Reconstruction. AB - Parallel imaging techniques are being applied in MRI to improve the spatial or temporal resolution. Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) is one of the most popular reconstruction techniques in parallel imaging. In GRAPPA, several k-space lines are acquired in addition to the normal subsampled data acquisition. Coil mapping information is extracted from these lines and used to reconstruct the missing k-space lines. These additionally acquired k-space lines can also be used in the final reconstruction so as to improve the image quality. In GRAPPA, carefully selecting the calibration region and sampling schemes can greatly reduce the noise and reconstruction artifact and improve the image quality. Perceptual Difference Model (PDM) is a quantitative image quality evaluation tool which has been successfully applied to varieties of MR applications. High correlation between human rating and PDM scores in previous studies shows that PDM is suitable for evaluating image quality in parallel MR imaging. We used PDM to quantitatively compare the quality of images reconstructed with different calibration regions and sampling schemes. We conclude that when the location of the calibration region is set at 0.8 of the phase encoding direction, and the width is set as 20% of total available fitting length, the best reconstruction image could be achieved. One should also set the outer region factor as small as possible. As an example, with all these optimizations, the time used to achieve the same image quality would be reduced by 16% as compared to unoptimized GRAPPA. PMID- 17281995 TI - Quadratic B-mode (QB-Mode) Ultrasonic Imaging with Coded Transmit Waveforms. AB - In this paper, the use of coded transmit waveforms with post-beamforming nonlinear filtering of echo data in diagnostic ultrasound is presented. The nonlinear filter based on the second-order Volterra filter (SoVF) model separates the linear and quadratic echo components. The grayscale representation of the latter results in a new mode of imaging we refer to as quadratic B-mode (QB mode). The use of chirp transmit waveforms in imaging contrast agents allows for nonlinear excitation of microbubble contrast agents (UCA) at a range of frequencies throughout the bandwidth of the transducer. The QB-mode image is shown to produce significant increase in UCA contrast over standard B-mode images from conventional and chirp excitation with and without compression. This contrast enhancement is achieved without loss in spatial resolution. PMID- 17281994 TI - Implementation of High-Temperature Superconducting tapes RF coils for 3T MRI system. AB - One way to reduce receiving coil noise in MRI scans is using non-resistive high temperature superconducting (HTS) coils [1]. They show advantages of much lower cost and easier fabrication over HTS thin iilm coils. In this work, we built a 200mm in diameter Bi2Sr2Ca2Cu3Ox(Bi-2223) tape HTS RF coil and demonstrated that the SNR of using the HTS tape coil was 2.22 folds higher than that of the traditional copper coil for a phantom MR study. Test results were in agreement with predictions, and the error of predicted SNR gains and measured SNR gains is about 0.9%. The HTS coil can be expected to generate higher SNR gain after optimization. In the future, in-vivo experiments will be conducted to farther test the capability of the HTS tape coil. Further applications functional MRI is under investigation to test the power of this HTSC system in our 3T system. PMID- 17281997 TI - Code compression after demodulation in ultrasound flow imaging systems. AB - In this paper, an ultrasound flow imaging system with single-transmit coded excitation is studied. With the oversampled code sequence modulated by base code, code compression before or after demodulation is demonstrated to be equivalent. A coded excitation flow imaging system with relatively low analog-to-digital (AD) sampling rate is proposed. The performance of the system is evaluated by simulation results. PMID- 17281996 TI - On the efficient estimation of blood velocities. AB - Pulsed wave (PW) Doppler ultrasound systems are commonly used to examine blood flow dynamics and the technique plays a very important role in numerous diagnostic applications. Commonly, narrow-band PW systems estimate the blood velocity using an autocorrelation-based estimator. Herein, we examine a recently proposed hybrid frequency estimator, and via extensive numerical simulations using simulated blood scatterers show the achievable performance gain of this method as compared to the traditional approach. PMID- 17281998 TI - Dynamic Intraoperative Prostate Brachytherapy Using 3D TRUS Guidance with Robot Assistance. AB - This paper describes a system for dynamic intraoperative prostate brachytherapy using 3D ultrasound guidance with robotic assistance. The system consists of 3D TRUS imaging, a robot and software for prostate segmentation, intraoperative planning, oblique needle segmentation and tracking, seed segmentation, and 3D dose planning. The robot and 3D TRUS coordinate systems are unified through robot and image calibrations. In 3D ultrasound images, the prostate is segmented using the discrete dynamic contour method, and optimal implantation plan is performed using geometric optimization followed by simulated annealing. The inserted needles are segmented and tracked using grey-level change in near real-time, and seed segmentation is performed using 3D line segment patterns. Needle placement accuracy of the robot at the "patient" skin was 0.15mm± 0.06mm, and needle angulation error was 0.07°. Needle targeting accuracy was 0.79mm±0.32mm. PMID- 17282000 TI - Ultrasound Evaluation of Mechanical Properties of Individual Muscles-Tendons during Active Contraction. AB - A new method to accurately measure the mechanical properties of individual muscles and tendons under active contraction is presented. An individual muscle is activated selectively to different intensities through electrical stimulation with adjustable amplitude, frequency, and pulse width. During the course of active contraction of the stimulated muscle, muscle fiber pennation angle, muscle fascicle length, tendon length are measured by ultrasonography in vivo and non invasively. The force produced by the stimulated muscle is derived from the measured joint torque and the moment arm recorded by a 3-D motion tracking system. The relationship between the force produced by the selected individual muscle and the muscle and tendon architectural parameters are studied quantitatively for the flexor carpi ulnaris and flexor carpi radialis. PMID- 17281999 TI - Automated segmentation of breast lesions in ultrasound images. AB - Breast cancer is one of the leading causes of death in women. As a convenient and safe diagnosis method, ultrasound is most commonly used second to mammography for early detection and diagnosis of breast cancer. Here we proposed an automatic method to segment lesions in ultrasound images. The images are first filtered with anisotropic diffusion algorithm to remove speckle noise. The edge is enhanced to emphasize the lesion regions. Normalized cut is a graph theoretic that admits combination of different features for image segmentation, and has been successfully used in object parsing and grouping. In this paper we combine normalized cut with region merging method for the segmentation. The merging criteria are derived from the empirical rules used by radiologists when they interpret breast images. In the performance evaluation, we compared the computer detected lesion boundaries with manually delineated borders. The experimental results show that the algorithm has efficient and robust performance for different kinds of lesions. PMID- 17282001 TI - Comparison of lumbar muscle sEMG between health and LBP patients during dynamic back extensions. AB - Nonlinear sEMG signal complexity and recurrence quantification analysis (RQA) methods together with the traditional linear spectrum analysis were used to compare the differences between non-specific chronic low back pain patients and healthy subjects, and to evaluate the active physical therapy effects on LBP patients during dynamic isoinertial extension test. PMID- 17282002 TI - The effect of changes in body mass distribution on feed-forward postural control: a pilot study. AB - In the past few decades, there has been a dramatic increase in the overweight and obese population. Relatively minimal research has addressed how drastic body weight changes that mimic going from normal to obese affect control of posture. The present work investigated the effects of changes in body mass on feed-forward postural control. The addition of extra weights simulated overweight and obesity conditions. Electromyogram (EMG) from leg and trunk muscles and force platform data were collected during a load catching task. EMG activities were integrated within typical time intervals to quantify feed-forward postural control. A 20% and 40% increase of the body weight was associated with larger feed-forward postural control and larger displacements of center of pressure (COP). PMID- 17282003 TI - A Study on Fitts' Law Based Gait Symmetric Evaluation and It's Clinic Application. AB - Symmetry, one of the prominent characters of normal human gait, could be destroyed by some special or abnormal factors such as barrier spanning, walking impediment, etc. Therefore, it becomes an important factor used to evaluate qualities and functions of walking. In this paper, the fitts' law based symmetry index calculation is introduced and its application in clinic test is also reported. The results show that the fitts' law based index is effective in clinic evaluation. PMID- 17282004 TI - Development of a Tool for Analyzing 3D Knee Kinematic Characteristics of Different Daily Activities. AB - This study provides a basic understanding of the kinematic characteristics of the knee during different daily activities based on a functional knee analyzer, which allows a three-dimensional evaluation of the knee in motion. The results showed that there was significant difference in knee motion between the patients with knee osteoarthritis (OA) and normal subjects during lunging, squatting and no weight-bearing knee flexion-extension. The data obtained by the knee analyzer was sensitive enough to distinguish young and middle-aged subjects from OA subjects during different daily activities; squatting gave the best results. On the other hand, the OA and elderly subjects had similar knee flexion and adduction angle profiles. This founding may partially explain the increased prevalence of OA in elderly people. The results support the use of functional knee analyzer for biomechanical analysis of daily activities, especially squatting, as a clinical evaluation tool for patients with knee osteoarthritis. PMID- 17282005 TI - First results of a complete marker-free methodology for human gait analysis. AB - This paper presents a complete methodology for human gait analysis using a marker free system. The acquisition system devised is composed of three synchronized and calibrated CCD cameras. The aim of this work is to recognize the leg of a walking human in gray level image sequences, to reconstruct it in the three dimensional space and then to analyze the movements of the body during gait activity. An articulated 3D model of the human body, based on tapered superquadric curves, is first introduced. A motion-based segmentation, using morphological operators is then applied to the image sequences in order to extract the boundaries of the leg in motion. A reconstruction process, based on the use of a Least Median of Squares (LMS) regression is next performed, in order to determine the location of the human body in 3D space. Finally, a spatial coherence is imposed on the reconstructed curves in order to better fit the anatomy of the leg and to take the articulated model into account. Each stage of the proposed methodology was tested both on synthetic images and on real world images of walking humans. After having reconstructed the 3D model of the human, some describing gait parameters were extracted and analyzed in order to detect pathologies or abnormalities. PMID- 17282006 TI - Computer Aided Detection of SARS Based on Radiographs Data Mining. AB - This paper introduces our work on how to use image mining techniques to detect SARS, the severe acute respiratory syndrome, automatically as the prototype of computer aided detection/diagnosis (CAD) system. Data used in this paper are digitalized PA(posterior anterior) X-ray images stored in the real-life picture archiving and communication system (PACS) of the 2nd Affiliation Hospital of Guangzhou Medical College. Association rule mining was applied first but results showed there was no significant difference between the locations of the lesions or infiltrate. Classification based on image textures was performed. A sample set contains both the pneumonia and SARS X-ray images was built in the first place. After modeling each sample by a feature vector, the sample set was partitioned to match the detection purpose: classification. Three methods were used: C4.5, neural network (NN) and CART. Final result shows that 70.94% SARS cases can be detected by CART. Data preparation, segmentation, feature extraction and data mining steps, with corresponding techniques are included in this paper. ROC charts and confusion matrix by all three methods are given and analyzed. PMID- 17282008 TI - Modelling the SARS epidemic by a lattice-based Monte-Carlo simulation. AB - We have analyzed the SARS data and the effect of the control measure in HongKong, based on a spatial Monte-Carlo model (SEIR) with susceptibles, exposed(latent), infective, and recovered. The SARS data can be well fit by numerical simulations. The control measure is effective to decreasing the transmission by reducing the contact rate. The average value of the reproductive number is consistent with many of the previous models. PMID- 17282007 TI - Characterizing Transmission and Control of the SARS Epidemic: Novel Stochastic Spatio-Temporal Models. AB - Severe Acute Respiratory Syndrome (SARS), the first epidemic of the 21st century, has an outbreak history of more than 2 years till today and caused tremendous damage to the human society. Accordingly, many studies on modeling the SARS epidemic have been reported, whereas deficiencies were still lying in those models because of their separate space/time methodology. In this paper, we propose novel comprehensive stochastic spatio-temporal models from both of the macro aspect and individual aspect for characterizing transmission and control of the SARS disease. Based on a new SARS spread process in consideration of "suspicious" population, we firstly establish the stochastic temporal models from two different aspects: the macro model is described with birth-death process and the individual Markov model is described with probability transition matrix (PTM). And then, we amalgamate the deterministic/stochastic population-flow model with the stochastic temporal models together to set up the comprehensive stochastic spatio-temporal models. Simulations on computer have evaluated the effect of various realistic parameters and control policies, and also have testified the accuracy and efficacy of the new models. Additionally, particular studies on the cases of Tsinghua University and Beijing City are presented. The comprehensive stochastic spatio-temporal models have considerably reduced the complexity plus errors as compared with previous works and will be able to characterize other various epidemics, e.g. Avian Flu. PMID- 17282009 TI - A Respiratory Tract Infection Index for SARS and Avian Influenza Outbreaks. AB - A respiratory tract infection index (RTII) was developed to predict potential outbreaks of infectious respiratory diseases in the community. The index incorporates a variety of meteorological conditions and air pollution factors. In the first phase of our study, we reviewed the index values around certain typical epidemiological events by retrospective calculation. The results showed that significantly high index values were recorded right before the occurrences of the events. This finding suggests that the RTII index appears to be a good indicator for public health officials and the public for taking early preventative measures against infectious respiratory diseases such as SARS and avian influenza. Further statistical analyses will be conducted in the second phase of the study to validate the efficiency and generality of the index. PMID- 17282010 TI - Nano-manipulation of single DNA molecules based on atomic force microscopy. AB - Nano-manipulation of single atoms and molecules is a critical technique in nanoscience and nanotechnology. This paper will focus on the recent development of the manipulation of single DNA molecules based on atomic force microscopy (AFM) in our laboratory. Precise manipulation has been realized including varied manipulating modes such as "cutting", "pushing", "folding", "kneading", "picking up", "dipping", etc. The cutting accuracy is dominated by the size of the AFM tip, which is usually 10nm or less. Single DNA fragments can be cut and picked up and then amplified by single molecule PCR. Thus positioning isolation and sequencing can be performed. PMID- 17282011 TI - The 3a Protein of SARS-coronavirus Induces Apoptosis in Vero E6 Cells. AB - An outbreak of severe acute respiratory syndrome (SARS) occurred in China and the first case emerged in mid November 2002. The etiologic agent of this disease was found to be a previously unknown coronavirus, SARS-CoV. The detailed pathology of SARS-CoV infection and the host response to the viral infection are still not known. The 3a gene encodes a non-structural viral protein which is predicted to be a transmembrane protein. In this study, we showed that the 3a protein was localized to the endoplasmic reticulum (ER) in 3a-transfected monkey kidney Vero E6 cells. In vitro experiments of chromatin condensation and DNA fragmentation suggest that the 3a protein may trigger apoptosis. Our data show that over expression of a single SARS-CoV protein can induce apoptosis in vitro. Thus GFP 3a fusion protein could also be used as a biosensor for monitoring the cytopathic features of SARS infection, e.g. lymphopenia, in animal model systems, similar to nucleocapsid and 7a proteins. PMID- 17282012 TI - Chemical sensing and control in cell & tissue bioreactors. AB - To meet needs in cell and tissue engineering bioreactors are evolving to allow cells and tissues to be cultured under precisely defined physical and chemical conditions. Many cell-tissue types are now being cultured, and considered in this work are chondrocytes, vascular endothelial cells, and smooth muscle cells. The culture processes are dynamic and optimisation requires monitoring of key process variables. The chemical sensing in cell and tissue bioreactors described here has the long term aim of achieving automatic optimal control. Invasive and non invasive electrochemical and optical systems are described for a wide range of target analytes (gases, ions, metabolites, hormones and proteins), but emphasis is on O2, pH, CO2and glucose. The sensing is performed with: (a) interrogation via the bioreactor wall; (b) probes placed within the cell culture chamber; (c) analysis within a shunt/sampling chamber. Analysis of culture medium is used for measurement of glucose and for proteins that are markers of cell biosynthetic behaviour. Optical absorbance and scatter of cells and tissues are also investigated for both chemical and structural analysis. PMID- 17282013 TI - Perfused microreactors for liver tissue engineering. AB - We developed scalable microreactors that foster the development of 3D microscopic pieces of tissue. By integrating microreactors, reservoirs, and pumps in the multiwell cell culture plate format, we created a high throughput cell culture system. However, in contrast to commonly used 2D static cell culture in multiwell plates, our new system allows 3D perfused cell culture. The system provides a means to conduct assays for toxicology and metabolism and can be used as a model for human diseases such as hepatic diseases, exposure-related pathologies, and cancer. PMID- 17282014 TI - Heterogeneous cytoplasmic calcium response in microvascular endothelial cells. AB - We investigated changes in calcium concentration in response to the administration of ATP and the onset of shear stress with cultured rat adrenomedulary endothelial cells (RAMECs, microvascular). A substantial heterogeneity in time and space in the calcium response was observed. The onset of shear stress induced calcium waves that originated from one or several cells and propagated to neighboring cells The application of uniform exogenous ATP produced similar heterogeneous calcium transients. The size of the responding groups was dependent on ATP concentration. The propagation of calcium waves induced by either ATP or shear stress challenge was significantly suppressed by suramin, a non-specific purinergic receptor blocker. We investigated some of the mechanisms leading to the heterogeneity, and the results indicated that the main source of variation is the heterogeneous distribution of purinergic receptor. The application of ATP or shear stress stimulates cells to release ATP causing an increase of [Ca2+]ivia purinergic receptor in the cells that have high sensitivity. Subsequently, additional ATP is released and the elevation of ATP concentration in the vicinity of the initially responding cells mediates the calcium propagation. These data suggest a mechanism by which ATP acts as an autocrine and paracrine mediator to integrate individual cell responses that result in coordination of vascular functions in situ. PMID- 17282015 TI - Theoretical and experimental studies on filtering tumor cells from blood cell mixtures with dam structure in microfluidic devices. AB - Here, a filter with series of pools and dams structures was designed and fabricated, utilizing size difference between tumor and blood cells. The cell mixtures were successfully filtrated out by the filter, and separation efficiency was up to 99.9%. To evaluate the filter, physical models were made to describe the behaviors of different cells in microfluidic systems. As the ability of cell deformation depends on both cells' size and excess surface index (ESI), we measured the excess membrane area of different cells, and got tumor cell's ESI is 61.7% ~ 81% comparing with red blood cell (RBC) (44%) and white blood cell (WBC) (84%~137%). Then from the formulas we deduced, we get the filtering limitations of RBC, WBC, and tumor cell are respectively, around 1.8μm, 1.0-1.6μm and 3.7-4.4μm for dam structure; and 1.3μm, 0.9-1.3μm and 3 3.4μm radius for pipes, which actually show conditions for separation. The accuracy and high flux of the filter provide possibilities to isolate cancer cells directly from the blood in real-time, which could become a potential therapy to cancers. PMID- 17282016 TI - Ice formation of vitrification solutions for cryopreservation of tissues. AB - Based on Boutron's semi-empirical crystallization theory, a quantitative microscopic imaging method was developed to determine the quantity of ice in thin films of vitrification solutions. A universal equation was obtained for various vitrification solutions. The new method was applied to determine the ice quantity and critical cooling rates for two new vitrification solutions. This new method has several advantages including the fact that it is cheaper than differential scanning calorimetry (DSC) and that it can be used to study vitrification solutions with critical cooling rates extending beyond the maximum cooling rate of a typical DSC system. PMID- 17282017 TI - Development of a Non-intrusive System to Monitor Radial PulseWave Velocity. AB - Understanding arterial distensibility has shown to be important in the pathogenesis of cardiovascular abnormalities like hypertension. It is also known that arterial pulse wave velocity (PWV) is a measure of the elasticity or stiffness of peripheral arterial blood vessels. However, it generally requires complex instrumentations to have an accurate measurement and not suited for continual monitoring. In this paper, it describes a simple and non-intrusive method to detect the cardiovascular pulse from a human wrist above the radial artery and a fingertip. The main components of this proposed method are a piezoelectric transducer and a photoplethysmography circuitry. 5 healthy adults (4 male) with age ranging from 25 to 38 years were recruited. The timing consistency of the detected pulsations is first evaluated and compared to that obtained from a commercial electrocardiogram. Furthermore, the derived PWV is then assessed by the predicted values attained from regression equations of two previous similar studies. The results show good correlations (p<0.05) and similarities for the former and latter respectively. The simplicity and non invasive nature of the proposed method can be attractive for even younger or badly disturbed patients. Moreover, it can be used for prolonged monitoring for the comfort of the patients. PMID- 17282018 TI - Temperature control for PCR thermocyclers based on peltier-effect thermoelectric. AB - In thermal cycling of polymerase chain reaction, the process recipe is characterized by high ramp rates and short temperature holds. In order to reduce the time taken to complete a standard PCR protocol, a model-based hybrid control configuration is designed to rapidly track the thermal cycling recipe. The hybrid control configuration consists of feedforward, feedback and Bang-Bang actions, of which, the feedforward control is a model predictive control action and improves the dynamic performance of temperature tracking significantly. The model of the thermocycler is identified with step response data at different operating regions. Experimental results demonstrate that the hybrid control strategy performs better than the conventional PID controller both in setpoint response and in steady-state performance of temperature control, so that the accuracy and efficiency of PCR are improved accordingly. PMID- 17282020 TI - Alpha-band characteristics in EEG spectrum indicate reliability of frontal brain asymmetry measures in diagnosis of depression. AB - Asymmetry in brain activity has been hypothesised to be a potential marker for depression. However, it is not yet fully understood nor is it reliable enough to be in regular clinical use. In this study frontal Electroencephalograph (EEG) recordings were taken from 21 subjects, from which Frontal Brain Asymmetry (FBA) ratios were calculated. The results were classified according to whether or not the subject had a recent history of depression, and by the presence or absence of a characteristic peak in the ;alpha' region of the EEG spectrum. It was found that subjects with current or previous incidence of depressive disorders tend to have an FBA ratio that lies towards the extremities of the distribution, and that the presence of a ;clear alpha peak' made the assessment process more reliable. PMID- 17282019 TI - Development of a novel method to determine human current perception threshold. AB - This paper reports a novel instrument for human current perception threshold (CPT) measurement. An objective galvanic skin response (GSR) method is employed to monitor subject's response to quantitative stimuli. Experimental results show that new system is more objective and easy to operate in comparison with conventional quantitative sensory testing systems. PMID- 17282021 TI - Relations between Physiologic Parameters and Pulse Transit Time during Loaded Breathing. AB - Pulse transit time (PTT) is a non-invasive measure, defined as time taken for the pulse pressure waves to travel from the R-wave of electrocardiogram to a selected peripheral site. Baseline PTT value is known to be influenced by physiologic variables like heart rate (HR), blood pressure (BP) and arterial compliance (AC). However, few quantitative data are available describing the factors which can influence PTT measurements in a child during breathing. The aim of this study was to investigate the effects of changes in breathing efforts on PTT baseline and fluctuations. Two different inspiratory resistive loading (IRL) devices were used to simulate loaded breathing in order to induce these effects. It is known that HR can influence the normative PTT value however the effect of HR variability (HRV) is not well-studied. Two groups of 3 healthy children (≤12years) were recruited; one group with insignificant (p>0.05) HR changes during all test activities. Results showed that HRV is not the sole contributor to PTT variations and suggest that changes in other physiologic parameters are also equally important. Hence, monitoring PTT measurement can be indicative of these associated changes during tidal or increased breathing efforts in healthy children. PMID- 17282022 TI - Enhancement of thermal diagnostics on tumors underneath the skin by induced evaporation. AB - Infrared imaging has frequently been used in clinics to detect changes in skin surface temperature associated with some superficial tumors. In order to accurately detect and diagnose tumors (especially in their early stages) using infrared thermography, enhancement of thermal expression on the skin over the tumor is desired. This study proposed a novel approach to effectively enhance the skin thermal expression of tumor by induced evaporation on skin surface. To illustrate its feasibility, numerical calculation was first applied to simulate the corresponding heat transfer process, from which the three-dimensional transient temperatures of the biological bodies subjected to induced evaporation were theoretically predicted. Further, preliminary infrared imaging experiments on human forearm were also performed, in which water and 75% (V/V) medical ethanol were particularly chosen to be respectively sprayed on the skin surface. Both the numerical and experimental results indicate that the induced evaporation can significantly enhance the sensitivity of temperature mapping on skin surface over the tumor. The results also suggest that the induced evaporation method can be used to improve the diagnostic accuracy of infrared thermography, especially for tumors at early stages and/or deeply embedded. PMID- 17282023 TI - Three-Dimensional Tracking of Single Granules in Living PC-12 Cells Employing TIRFM and WFFM. AB - A comparative study was carried out on evaluating the performance of total internal reflection fluorescence microscopy (TIRFM) and deconvolution wide-field fluorescence microscopy (WFFM) in tracking single secretory granules. Both techniques have been applied to follow the three-dimensional mobility of single secretory granules in living neuroendocrine PC-12 cells. Both techniques return the similar result that most acridine orange-labeled granules were found to travel in random and caged diffusion, and only a small fraction of granules traveled in directed diffusion. Furthermore, the size and 3-D diffusion coefficient of secretory granules, obtained by these two imaging techniques, yield the same value. Together, our results demonstrate the potential of the combination TIRFM and WFFM in tracking long-termed motion of granules throughout live whole cells. PMID- 17282024 TI - Iris recognition based on adjustable scale wavelet transform. AB - This paper represents a new method for iris recognition using the bandpass characteristic of wavelets and wavelet transform principles for detecting singularities. The iris image texture is divided into eight bands, and each band is processed to generate a 1-D intensity signal. The appropriate scale wavelet is used to filter each signal for quantization to 256 byte iris feature codes. Then the Hamming distance is adopted to match two iris codes. In particular, the appropriate scale for each signal is searched for by minimizing the Hamming distance. The results show that the performance of this method is better than some algorithms. Meanwhile, it is translation, rotation, and scale invariant, so it is promising to be used in a personal identification system. PMID- 17282025 TI - Application of neural networks in the interpretation of impedance cardiovasograms for the diagnoses of peripheral vascular diseases. AB - An Impedance Cardio-vasograph (ICVG) system has been developed at the Electronics Division, Bhabha Atomic Research Centre (B.A.R.C) for the assessment of Peripheral Blood Flow and has been installed at the Department of Medicine, J.J. Hospital, Mumbai, India. Impedance cardio-vasography (ICVG) gives an indirect assessment of blood volume changes by measurement of normalized rate of change of electrical impedance (N dZ/dt) of the body segment. Parameters like Blood Flow Index (BFI) and Differential Pulse Arrival Time (DPAT) at different locations in both lower extremities (upper thigh, knee, calf and ankle) can be computed from these measurements. This work deals with the analysis of these parameters by a neural network system for obtaining proper diagnosis of subjects with peripheral vascular diseases. The designed network identified the presence of anatomical block or narrowing for most of cases presented to it during testing and also the status of collateral circulation in the lower limbs. The neural network was trained again, with the few cases, which were not predicted correctly. The collaterals after the site of occlusion were classified as good, moderate or poor as an aid to the physician. The network identified cases with athero-sclerotic narrowing satisfactorily and was also able to categorize cases where changes are observed only in one extremity, other remaining normal as in the cases of hemi Leriche's syndrome. An additional parameter CVS (Coefficient of venous Statis) was calculated which is useful for the diagnosis of primary and secondary varicosity of the veins. PMID- 17282026 TI - Investigation of the mechanisms of electromagnetic field interaction with proteins. AB - In our earlier work we have proposed that protein activation is electromagnetic in its nature. This prediction is based on the Resonant Recognition Model (RRM) where proteins are analyzed using digital signal processing (DSP) methods applied to the distribution of free electron energies along the protein sequence. This postulate is investigated here by applying the electromagnetic radiation to example of L-Lactate Dehydrogenase protein and its biological activity is measured before and after the exposures. The concepts presented would lead to the new insights into proteins susceptibility to perturbation by exposure to electromagnetic fields and possibility to program, predict, design and modify proteins and their bioactivity. PMID- 17282027 TI - 3D ROC Analysis for Medical Imaging Diagnosis. AB - Receiver operating characteristics (ROC) has been widely used as a performance evaluation tool to measure effectiveness of medical modalities. It is derived from a standard detection theory with false alarm and detection power interpreted as false positive (FP) and true positive (TP) respectively in terms of medical diagnosis. The ROC curve is plotted based on TP versus FP via hard decisions. This paper presents a three dimensional (3D) ROC analysis which extends the traditional two-dimensional (2D) ROC analysis by including a threshold parameter in a third dimension resulting from soft decisions, (SD). As a result, a 3D ROC curve can be plotted based on three parameters, TP, FP and SD. By virtue of such a 3D ROC curve three two-dimensional (2D) ROC curves can be derived, one of which is the traditional 2D ROC curve of TP versus FP with SD reduced to hard decision. In order to illustrate its utility in medical diagnosis, its application to magnetic resonance (MR) image classification is demonstrated. PMID- 17282028 TI - Muscle activity onset time detection using teager-kaiser energy operator. AB - This study presents a novel method, characterized with simple implementation, to automatically detect the onset time of muscle activity using surface electromyogram (EMG) signals. The method applied Teager-Kaiser energy operator (TKEO) to highlight the motor unit activities by simultaneously considering the amplitude and frequency information of the surface EMG, and therefore increase the prospects of muscle activity detection. A robust threshold-based algorithm was then applied to the TKEO output to locate the onset time of muscle activity. The validity of the proposed method was illustrated using both experimental surface EMG recordings and various surface EMG simulations. PMID- 17282029 TI - Respiratory wheeze detection system. AB - Respiratory sound is associated with many lung diseases. By observing respiratory sound symptoms, we can know more about lung conditions. In this research, we construct an efficient lung sound recording system according to CORSA, and develop a spectrogram process flow technique to object wheeze. It is a low cost and efficient system. In clinic test, we also can precisely objective wheeze up to about 89%. PMID- 17282030 TI - Modeling of pulmonary crackles using wavelet networks. AB - In this study, wavelet networks are used to model pulmonary crackles with a view to extract features for the classification analysis of crackles obtained from subjects with a wide spectrum of pulmonary disorders. Crackles are very common adventitious sounds which are transient in character and whose characteristics, such as type, number of occurrence and pitch, convey information regarding the type and severity of the pulmonary disease. Crackles generally start with a sharp deflection and continue with a damped and progressively wider sinusoidal wave. In this study, due to the capability of time-frequency representation of wavelet functions, wavelet network (WN) is employed to characterize crackles, and the parameters acquired from wavelet nodes are used to distinguish them into two clinical classes, i.e. fine and coarse. For this purpose, a wavelet function (complex Morlet) in the first node is trained to fit the crackles and the second wavelet node is tuned to represent the error of the first node. Both of the nodes are, then, trained to minimize the total representative error. The five parameters of the WN node, i.e. scaling, time-shifting, frequency and two weight factors of sinus and cosines components are used as features in the classification analysis of crackles. The crackle information is strongly represented by the first wavelet node, therefore, the parameters belonging to the first node are used in the classification of crackles. PMID- 17282031 TI - Compression of ECG as a Signal with Finite Rate of Innovation. AB - Compression of ECG (electrocardiogram) as a signal with finite rate of innovation (FRI) is proposed in this paper. By modelling the ECG signal as the sum of bandlimited and nonuniform linear spline which contains finite rate of innovation (FRI), sampling theory is applied to achieve effective compression and reconstruction of ECG signal. The simulation results show that the performance of the algorithm is quite satisfactory in preserving the diagnostic information as compared to the classical sampling scheme which uses the sinc interpolation. PMID- 17282032 TI - Coupling wavelet transform with bayesian network to classify auditory brainstem responses. AB - In this work, a method that combines wavelet transform and Bayesian network is developed for the classification of the auditory brainstem response (ABR). First the wavelet transform is applied to extract the important features of the ABR by thresholding and matching the wavelet coefficients. A Bayesian network is then built up based on several variables obtained from these significant wavelet coefficients. In order to evaluate the performance of this approach, stratified 10-fold cross-validation is used and the network is evaluated on subject dependent test sets (drawn from the same subjects from which the training set was derived). In particular, the data analyzed here are the ABR data with only fewer repetitions (64 or 128 repetitions) and this offers the great advantage of reducing the total time of recording, which is very beneficial to both the clinicians and the patients. Finally, a preprocessing method based on Woody averaging is applied to adjust the latency shift of the ABR data and it enhances the results. PMID- 17282033 TI - Feature extraction based on mel-scaled wavelet transform for heart sound analysis. AB - To provide a robust representation of heart sound signal in an automatic heart disease diagnosis system, a melscaled wavelet transform has been developed. It combines the advantages of linear perceptual scale by mel mapping with the suitability of analyzing non-stationary signals by wavelet transform. The heart sound signal is firstly divided into windowing frames. A set of mel-scaled filterbank is then used to calculate the mel-warped spectrum, which is followed by a wavelet transform to extract the mel-scaled wavelet features. The performance of the proposed algorithm is evaluated for heart sound analysis using clean and noisy data, and compared with the standard mel-frequency cepstral coefficients. Results show that the proposed approach provides a robust representation of heart sound signal in noisy environment. PMID- 17282034 TI - Tracking tremor frequency in spike trains using the extended kalman filter. AB - Tremor is one of the most disabling symptoms in patients with many movement disorders including Parkinson's disease (PD) and essential tremor (ET). Neural tremor, which is measured by microelectrodes placed near nerve cells or obtained from brain cells during stereotactic neurosurgery, is due to the fluctuation of the firing rate of neurons. The frequency of this neural tremor varies over time and is nonstationary. We describe a frequency tracking method using the extended Kalman filter (EKF) to estimate the instantaneous tremor frequency (ITF) of binary spike trains detected from microelectrode recordings (MER). The results demonstrate that the EKF can accurately track fluctuations in tremor frequency even though the noise in binary spike trains is not Gaussian. PMID- 17282035 TI - A Model of NO/O2Transport in Capillary-perfused Tissue Containing an Arteriole and Venule Pair. AB - The goal of this study was to investigate the complex co-transport of nitric oxide (NO) and oxygen (O2) in a paired arteriole-venule, surrounded by capillary-perfused tissue using a computer model. Blood flow was assumed to be steady in the arteriole and venular lumens and to obey Darcy's law in the capillary-perfused tissue. NO consumption rate in the arteriolar and venular lumen was assumed to be constant in the core of the arteriolar and venular lumen and to decrease linearly to the endothelium. Average NO consumption rate by capillary blood in a unit tissue volume was assumed proportional to the blood flux across the volume. Our preliminary results predict that: 1) The capillary bed, which connects the arteriole and venule, facilitates the release of O2 from the vessel pair to the surrounding tissue; 2) Decreasing the distance between arteriole and venule can result in a higher NO concentration in the venular wall than in the arteriolar wall; 3) In the absence of capillaries in the surrounding tissue, diffusion of NO from venule to arteriole contributes little to NO contents in the arteriole; and 4) when capillaries are added to the simulation, a significant increase in arteriole NO content is observed. PMID- 17282036 TI - Study of Interaction Force between Antigen and Antibody using Flow Chamber Method. AB - A parallel plate flow chamber was used to study the interaction force between human IgG (immobilized on a chip surface as ligand) and goat anti-human IgG (immobilized on microspheres surface as receptor). First, it was demonstrated that the binding force between the microspheres and the chip surface came from the bio-specific interaction between the antigen and the antibody. Secondly, it was obtained that the critical shear rate to detach microspheres from the chip surface increases with the ligand surface concentration. Finally, two models to estimate the antigen-antibody bond strength considering bonds' positions were proposed and analyzed. PMID- 17282037 TI - DNA base excision repair nanosystem engineering: model development. AB - DNA base damage results from a combination of endogenous sources, (normal metabolism, increased metabolism due to obesity, stress from diseases such as arthritis and diabetes, and ischemia) and the environment (ingested toxins, ionizing radiation, etc.). If unrepaired DNA base damage can lead to diminished cell function, and potentially diseases and eventually mutations that lead to cancer. Sophisticated DNA repair mechanisms have evolved in all living cells to preserve the integrity of inherited genetic information and transcriptional control. Understanding a system like DNA repair is greatly enhanced by using engineering methods, in particular modeling interactions and using predictive simulation to analyze the impact of perturbations. We describe the use of such a "nanosystem engineering" approach to analyze the DNA base excision repair pathway in human cells, and use simulation to predict the impact of varying enzyme concentration on DNA repair capacity. PMID- 17282038 TI - An accurate surface formulation for biomolecule electrostatics in non-ionic solutions. AB - The electrostatic interactions between biomolecules and solvent are generally difficult to model because there exist an enormous number of solvent degrees of freedom. Continuum electrostatic models provide an approximate method to analyze these interactions; these models are typically solved numerically in either differential or integral form. In this paper we demonstrate the importance of using an appropriate numerical technique, called qualocation, for a popular integral formulation of the electrostatics problem. Numerical results illustrate that qualocation exhibits superior accuracy relative to naive implementations. We also show that the integral formulation is extremely well-conditioned and converges rapidly when iterative methods are used to solve the discretized integral equation. PMID- 17282039 TI - A quantitative description of conductance of human stratum corneum caused by pulse electrical field. AB - it is expounded the properties of conductance changes of the stratum corneum (SC) under the electric pulse field. It is considered that conductance for SC is determined by activation and inactivation factors. With the diffusion chamber as system, and the SC from cadaver as the object, we studied the behavior of the conductance change under the electric pulse field. The results show that theoretical curves of conductance on SC are fitted very well with the data from these experiments. So the conclusion is that these parameters of activation factor and inactivation factor (m0, m,m, Tm, h0, h, and Th) are believed to be a very important significance for the analysis of drug transport through skin. PMID- 17282040 TI - Design proposal of imaging activities of cultured neural network on a silicon substrate with neural-electronic-optical integrated microsystem. AB - Multielectrode Arrays have currently been widely used as Neural-Network research tools. In this paper, we propose a novel mixed integrated sensor array microsystem combining cultured biological neurons, silicon integrated circuits and optical components together on a single silicon substrate. Using the light emitting property of GaAs-LED dependent on current passing from the recorded action potentials signals by a Multielectrode-Array in situ, we are able to characterize the neural activities of the cultured neural networks directly with a visible image displayed by a monitoring CCD Camera. Researchers may use various ready image process tools for experimental data analysis to directly observe results. PMID- 17282042 TI - Impedance spectroscopy analysis of cell-electrode interface. AB - Many chronically implanted electrodes suffer sensitivity loss in their applications in brain computer interface systems. It is hard to diagnose the cause of the problem because few measures are available to analyze directly what happened on the cell-electrode interface. In this paper, the impedance characterization of the cell-electrode interface was discussed in detail using equivalent circuit approach, which was used to evaluate the cause of the electrode sensitivity loss. The impedance spectroscopy of the cell-electrode interface acts as a function of several parameters, such as the sealing resistance and the shunt capacitance between the microelectrode and the electrolyte. Changes of the impedance spectroscopy can be traced to the parameter changes of the equivalent circuit, which reflect the status of the cell-electrode interface, such as the cell-electrode gap change, the erosion of microelectrodes, and so on. The circuit impedance simulation results give an important reference for the monitor of the cell-electrode connection, and are also helpful for the improvement of the microelectrode design. PMID- 17282041 TI - Synaptic connectivity of a low density patterned neuronal network produced on the poly-L-lysine stamped microelectrode array. AB - Rectangular networks of rat hippocampal neurons have been produced on microelectrode arrays (MEAs). The crossing points of networks were located at the recording electrode sites by aligned microcontact printing (μCP) technique. Polydimethysiloxane (PDMS) stamp was fabricated to print fine poly-L-lysine (PLL) patterns of 2 -width lines for neurites and 20 -diameter circles for cell bodies. Different densities of neurons were applied on the PLL-stamped MEAs to find how a low density of neurons still has the functional connectivity. From the neural network applied with a density of 200 cells/mm2, we could observe signal propagation among spontaneous activities. Electrical responses were also evoked by 200 current pulse stimulation with 50 pulse width. Immunocytostaining was employed to identify dendrites, synapses, and nuclei in the patterned neurons. PMID- 17282043 TI - In-vitro testing of simultaneous charge injection and recovery in a retinal neuroprosthesis. AB - In order to deliver sufficient phosphene quantities to convey effective vision in a prosthesis device, simultaneous stimuli is necessary. We present in vitro experimental results of the current distribution between stimulation sites during simultaneous stimulation of platinum electrodes immersed in physiological saline. Stimuli were delivered using circuitry that utilizes (a) current source only, (b) current sink only, and (c) the combination of a balanced current source and current sink, to deliver and recover balanced charge at each stimulation site. The results from these experiments support our decision to implement balanced combined current source and current sink circuitry in an application specific integrated circuit (ASIC). PMID- 17282044 TI - Evaluation of flow rate estimation method for rotary blood pump with chronic animal experiment. AB - Rotary blood pumps are expected to be used as an implantable ventricular assist device (VAD). In the VAD system, flow rate is important for monitoring of the state of a recipient and for automatic control to maintain appropriate blood perfusion. To obtain flow rate of the pump without any sensors, we proposed a method of estimating flow rate with supplied power and rotational speed using a time series model. To evaluate the accuracy of the proposed estimation method from the aspect of long-term use, we implanted NEDO PI Gyro pumps in a calf and performed a chronic animal experiment. Flow rate, supplied power and rotational speed were measured until post operation day (POD) 63, and the estimated flow rate was compared with the measured one. We confirmed that waveforms of the measured flow rate was sufficiently similar to the measured one, and correlation between them was higher than 0.9 in all the datasets. On the other hand, the root mean square error increased after 15 days. This error was probably due to the change in physiological condition, the operating point of the pump, or mild intima formation. PMID- 17282045 TI - Experimental and Computer-Based Performance Analysis of Two Elastomer VAD Valve Designs. AB - The development of a new generation pneumatic Ventricular Assist Device (VAD) required the design of valves for the optimization of its performance. Experiments and computer-based simulations under hydrostatic conditions were analyzed in order to test and compare two low-cost elastomer valve designs. The trileaflet valve design showed a superior hydrostatic performance, having almost a ratio of 1:2 hydraulic resistance than the bileaflet valve design in agreement with both, the experimental and the simulation evidences. This study will address the use of a trileaflet valve designs in the future VAD redesign. PMID- 17282046 TI - Physiome model based cardiac information recovery under multiframe state-space framework. AB - In patient-specific cardiac information recovery, meaningful a priori models for constraining the sparse and noise-corrupted measurements, and also the optimal criteria for coupling them together, are essential for obtaining more reliable estimates. Although the extensively used biomechanical models give promising results, it cannot account for the active components of the myocytes. In view of this, we propose to adopt a cardiac physiome model, which is composed by a cardiac electric wave propagation model, an electro-mechanical coupling model, and a biomechanical model, for a more complete modeling of the cardiac physiology. Under the multiframe state-space filtering framework, the physiome model is coupled with the measurements to provide the optimal estimates of the cardiac information. Experiments have been performed on both synthetic and MRI data to illustrate its abilities and benefits. PMID- 17282047 TI - Cardiac dysfunction investigation in prehypertension. AB - To study the possible cardiac function alternation in hypertension, 13 cardiac function parameters such as blood pressure (BP), cardiac output (CO), ejection time (ET) and stroke volume (SV), etc. were measured in 898 subjects. The subjects were grouped into 3 groups by blood pressure, namely: normotension, prehypertension and hypertension group. Statistic analyses showed that in prehypertension subjects, peak velocity and cardiac output increased, while the systemic vascular resistance index had no significant increase compared with normotensive. Peak velocity, mean pressure gradient and velocity time integral in prehypertension were significantly correlated with systolic blood pressure, however, no correlation was found in either normotension or hypertension subjects. The results suggest that increasing cardiac output and peak velocity occurred at the phase of prehypertension, which may conduce to the elevation of blood pressure. PMID- 17282049 TI - Non-invasive monitoring of left ventricular contractility and ventilatory mechanics. AB - The maximum left ventricular elastance (Emaxiv) is a valuable index of ventricular contractility. However, conventional methods for its measurements are too invasive for routine use. We propose a non-invasive technique for tracking changes in Emaxivby mathematically determining the dynamic coupling between beat-to-beat fluctuations in instantaneous lung volume and arterial blood pressure measured during random interval breathing. The mathematical technique also provides an estimate of the dominant time constant of the ventilatory system (), which is equal to the product of the airway resistance and lung compliance. We then describe a theoretical evaluation of the technique with respect to realistic beat-to-beat variability generated by a cardiovascular simulator. Our results show that the technique is able to detect actual changes in the Emaxivand values of the simulator. With successful experimental testing, the technique may ultimately be employed to help guide therapy in heart failure patients. PMID- 17282048 TI - Simulation algorithm for the coupling of the left ventricular mechanical model with arbitrary circulation model. AB - The left ventricular mechanical model and the circulation model are important for the cardiovascular dynamics simulation that consider the characteristics of the ventricular cells and the structure of left ventricle (LV). Due to the fact that the cardiovascular dynamics is the result of nonlinear interactions between these two models, simultaneous consideration of both models using a strong coupling method is necessary for an accurate simulation. In this paper, we propose a simulation algorithm that is capable of calculating cardiovascular dynamics model by strong coupling of the left ventricular mechanical model and the circulation model. PMID- 17282051 TI - Control of skeletal muscle force with currents injected via an intrafascicular, microelectrode array. AB - In spinal cord injured patients, the reanimation of dysfunctional limbs has been achieved with extrinsic stimulation of skeletal muscle via surface, epimysial, and nerve cuff electrodes. However, these neural interfaces have a number of significant problems that are mitigated by the use of electrodes that are inserted directly into the nerves that innervate targeted muscles. These problems, and their mitigation by one embodiment of an intrafascicular electrode array, the Utah Slanted Electrode Array, are the subject of this paper. PMID- 17282050 TI - An innovative approach to evaluate a cardiac function based on surface measurement. AB - Major function of the heart is to pump blood flow up to all tissues or organs in the body, and it is generally recognized that cardiac function under various diseased conditions are mainly represented by a relationship between blood flow and pressure inside of the heart. In this report, an original proposal of evaluation method on cardiac function is introduced through a simultaneous measurement of various points of cardiac muscular surface. An optical three dimensional location sensor was employed to measure a displacement change of anatomically specific points on heart surface. Then, changes in strain in each regional surface area were quantitatively obtained. This result indicated similar tendency obtained from echocardiogram. It was also indicated that there was a difference in displacements and phrases between control and arrhythmia. Moreover, strain change in regional area was coincident with a contraction of natural heart. It was found that an attempt to superimpose the data of strain change onto the video images of natural heart was extremely helpful to understand a cardiac function visually. PMID- 17282052 TI - Life-like Control for Neural Prostheses: "Proximal Controls Distal". AB - We describe the model and implementation of the hierarchical hybrid method for controlling of the lower-arm (pronation/supination and elbow flexion/extension) in humans with disabilities. The control follows the strategy found in ablebodied humans where the movement is planned based on the task and the most distal part of the arm; yet, the command starts from the most proximal segment. The controller uses a black box of the movement and relies on temporal and spatial synergies. The driving signals are the shoulder flexion/extension velocity and acceleration, the outputs are four stimulation patterns for the control of elbow flexion/extension and pronation/supination. The operation is discrete at the voluntary and coordination levels, and continuous at the actuator level. The repertoire of movement that were considered was limited to a set of typical daily activities within the normal workspace in the sitting position only. The main application of this control is the therapeutic electrical stimulation in post stroke hemiplegic patients. PMID- 17282053 TI - Prosthetic command signals following targeted hyper-reinnervation nerve transfer surgery. AB - High-level upper-limb amputations result in prostheses with many degrees-of freedom to be controlled, with very few control signals. A novel method for the control of myoelectric upper limb prostheses has been developed. By transferring the residual nerves to spare muscles in or near the residual limb, additional myoelectric control signals are created that allow the simultaneous control of multiple degrees-of-freedom in the prostheses. Since the nerve function correlates physiologically to the prosthetic function, operation is more natural and thus easier than current control paradigms. This surgical procedure and subsequent prosthetic fitting have been successfully completed on one shoulder disarticulation and one transhumeral amputee. The shoulder disarticulation amputee has also been fit with a unique 6 motor system, allowing him to control 3 motors (hand, elbow, and humeral rotator) with the use of 6 myoelectric signals; there was marked increase in functional range-of-motion. He was able to control multiple joints simultaneously and could perform tasks that he could not do before, including reaching out to pick up objects. PMID- 17282054 TI - Demand-controlled desynchronization of brain rhythms by means of nonlinear delayed feedback. AB - We present a novel method for desynchronization of strongly synchronized population of interacting oscillators. It is based on nonlinear delayed feedback, works on demand with vanishing amount of stimulation, and is robust with respect to parameter variations. We suggest our method for mild and effective deep brain stimulation in neurological diseases characterized by pathological cerebral synchronization. PMID- 17282055 TI - Cortically controlled brain-machine interface. AB - Over the past ten years, we have tested and helped develop a multi-electrode array for chronic cortical recordings in behaving non-human primates. We have found that it is feasible to record from dozens of single units in the motor cortex for extended periods of time and that these signals can be decoded in a closedloop, real-time system to generate goal-directed behavior of external devices. This work has culminated in a FDA clinical trial that has demonstrated that a tetraplegic patient can voluntarily modulate motor cortical activity in order to move a computer cursor to visual targets. Further advances in BMI technology using non-human primates have focused on using multiple modes of control from signals in different cortical areas. We demonstrate that primary motor cortical activity may be optimized for continuous movement control whereas signals from the premotor cortex may be better suited for discrete target selection. We propose a hybrid BMI whereby decoding can be voluntarily switched from discrete to continuous control modes. PMID- 17282056 TI - A novel wavelet-statistics based feature detection system for detecting microcalcifications. AB - This paper describes a wavelet-statistics based feature detection system as applied to microcalcification detection. While a number of researches have been conducted towards microcalcification detection using wavelet analysis and auxiliary information, most of this auxiliary information was obtained from within the spatial domain. In this research, a continuous wavelet transform was used to segment features and compute energy maps of these segmented features. The kurtoses of these features were computed in the wavelet domain. This statistical information together with the energy maps forms the inputs to a rule-based classifier. Physiological information from the spatial domain was used to exclude false-positives. The system was tested using a ROI from the LLNL database. The result is one false-positive within the cluster as classified by the radiologist. PMID- 17282057 TI - An improved articulated registration method for neck images. AB - This paper presents a complete method estimating the displacement field of bodies constrained by an articulated model such as the neck area. Indeed bony structures between different patient images, such as vertebras, may rigidly move while other tissues may deform. The method is divided into 3 steps. The method first registers the articulated rigid bodies together. Then it propagates the deformation into the whole volume through the use of a tetrahedral mesh and it finishes the registration using a mutual information based optical flow. Following the ITK framework, it uses a fast stochastic gradient descent optimization strategy chosen to maximize the mutual information metric. We demonstrate this method provides accurate results on 3D CT, MR and PET images. PMID- 17282058 TI - Stochastic inverse consistent registration. AB - An essential goal in medical image registration is, the forward and reverse mapping matrices should be inverse to each other, i.e., inverse consistent. Conventional approaches enforce such consistency in deterministic fashions, either through incorporation of sub-objective cost function to impose consistent property during the registration process or by construction of consistent mapping on predetermined landmarks sets. Assuming that the initial forward and reverse matching matrices have been computed and used as the inputs to our system, this paper presents a stochastic framework which yields perfect consistent registration. During the optimization process to reach the perfect consistency, we model the errors of the registration matrices and the imperfectness of the consistent constraint as stochastic processes. An iterative generalized total least square (GTLS) strategy has been developed so that consistency is optimally imposed. PMID- 17282059 TI - Performing Accurate Rigid Kinematics Measurements from 3D in vivo Image Sequences through Median Consensus Simultaneous Registration. AB - While focusing at accurate 3D joint kinematics, this paper explores the problem of how to perform a robust rigid registration for a sequence of object surfaces observed using standard 3D medical imaging techniques. Each object instance is assumed to give access to a polyhedral encoding of its boundary. We consider the case where object instances are noised with significant truncations and segmentation errors. The proposed method aims to tackle this problem in a global way, fully exploiting the duality between redundancy and complementarity of the available instances set. The algorithm operates through robust and simultaneous registration of all geometrical instances on a virtual instance accounting for their median consensus. When compared with standard robust techniques, trials reveal significant gains, as much in robustness as in accuracy. The considered applications are mainly focused on generating highly accurate kinematics in relation to the bone structures of the most complex joints - the tarsus and the carpus - for which no alternative examination techniques exist, enabling fine morphological analysis as well as access to internal joint motions. PMID- 17282060 TI - Multilevel Medical Image Fusion using Segmented Image by Level Set Evolution with Region Competition. AB - In this paper, a region level based image fusion technique, using wavelet transform, has been implemented and analyzed. The proposed methodology considers regions as the basic feature for representing images and uses region properties for extracting the information from them. A segmentation algorithm is proposed for extracting the regions in an effective way for fusing the images. The fusion strategy uses multi - level decomposition of the images obtained using wavelet transform. By analyzing the images at multiple levels, the proposed method is able to extract finer details from them and in turn improves the quality of the fused image. The performance and relative importance of the proposed methodology is investigated using the Mutual Information criteria. Experimental Results show that the proposed method improves the quality of the fused image significantly for both the normal and multifocused images. PMID- 17282061 TI - Biomedical Image Analysis in High-speed Laryngeal Imaging of Voice Production. AB - High-speed laryngeal imaging (HSLI) is emerging as a new clinical tool for the assessment of voice disorders. The analysis of high temporal resolution images of the vibrating vocal folds may provide new information on the mechanism of voice production and how altered vibratory properties relate to voice pathologies. An essential procedure in the HSLI data processing is tracing the vocal fold edges, an operation referred to as glottal edge detection. In this paper, we present an adaptive image segmentation method which facilitates fast and effective glottal edge detection operating on a frame-by-frame basis. The glottal area waveform traced from this process is then analyzed using an analytic signal approach we previously developed. In this approach, the analytic phase trace plot, or refereed to as Nyquist plot, is used to show patterns of the vocal fold vibration that correlate with voice quality and health condition. Several examples of clinical voice recordings are used to evaluate and test the effectiveness of our approach. PMID- 17282062 TI - Internal model approach for gait modeling and classification. AB - In this paper, we present a novel approach to model and classify gait patterns based on internal models. An internal model consists of two sets of differential equations and a neural network in between. It can effectively describe dynamic movement primitives (DMP), hence is able to model the temporal-spatial gait patterns. An interesting feature of the internal model is, the nonlinear map generated by the neural network can also serve the purpose for gait pattern classification. In this work we use a single hidden layer feedforward network (SLFN), and show that the characteristics of gait patterns can be captured via the output layer weights. The experiment results based on EMGs of gait patterns at five different walking speeds are used to validate the internal model approach. PMID- 17282063 TI - A model of length increases of the pectoralis major muscle to provide rehabilitation precautions for patients after mastectomy. PMID- 17282064 TI - A framework for linking gait characteristics of patients with accelerations of the waist. AB - This paper describes a framework for the analysis of accelerometer data as part of research undertaken in preparation for a clinical trial involving ambulatory monitoring of elderly rehabilitation patients. In particular we examine the response of side-mounted accelerometers to various gait patterns and attempt to establish a relationship with a biomechanical model for human gait. We explore the use of a linear predictive (LP) model as a basis for identifying key harmonic frequencies in the accelerometer response signals and use these harmonics to relate measured data back to harmonic predictions from the biomechanical model. PMID- 17282066 TI - Visual EMG Biofeedback to Improve Ankle Function in Hemiparetic Gait. AB - Spasticity in stroke patients interferes with coordinated muscle firing patterns of the lower extremity leading to gait abnormalities. The goal of this study was to improve ankle function during walking by augmenting treadmill gait retraining with a visual EMG biofeedback technique. Eight stroke patients who could ambulate between 0.5 and 0.9 m/s participated in the study. The training consisted of 12 sessions of treadmill walking during which the activity of the tibialis anterior and gastrocnemius lateralis muscles of the affected side was displayed on a computer screen. Targets were shown to indicate to the subject when to activate the monitored muscles. Gait evaluations were performed before and after the training period to test the hypothesis that ankle mechanics improved following the intervention. Improvements in gait function were characterized by changes in temporal gait parameters and lower extremity kinematics and kinetics. Subjects showed an increase in gait speed, time of single leg support on the affected side, ankle power generation at push-off and a reduction in knee extensor moment. These results indicate that treadmill gait retraining augmented via visual EMG biofeedback facilitates improvements in hemiparetic gait. PMID- 17282065 TI - A parametric investigation of swing motion triggered by electrical stimulation in paraplegic patients using response surface method. AB - We identified torque response of flexion reflex associated with hip angle and angular velocity in 6 subjects with chronic SCI and developed two dimensional dynamic model with three segments, thigh, shank and foot. Influences of stimulation parameters such as amplitude, frequency and duration time of pulse train for producing swing motion of lower limb were investigated with response surface method to obtain optimal solutions. The initial hip flexion velocity (F value > 19.0) and knee flexion velocity (F-value > 9.0) were clearly significant, while the initial hip angle was indistinguishable from the estimated amount of error. When the limb motion was simulated with initial hip and knee flexion velocity, the stimulation amplitude was increased 53%, the frequency was decreased 37% and the duration time was decreased 33% with respect to no initial condition. PMID- 17282067 TI - Endurance training of trained athletes-an electromyogram study. AB - Little is known about the mechanism that improves the capabilities of athletes by high, intensity interval training (HIT). This study was conducted to determine the neurophysiological changes due to HIT. Changes in surface electromyography (SEMG) in well-trained endurance cyclists due to the training were identified. Seven subjects (maximal oxygen uptake [VO2max] 64.6 ±4.8 ml.kg-1.min-1, mean ± SD) undertook a 3 week training intervention, replacing ∼ 15% of their weekly endurance training with 6 sessions of laboratory-based HIT (8 × 5 min work bouts at 82% of PPO [∼85% VO2max], with 60 sec active recovery at 100 W). SEMG was used to assess neuromuscular changes before and after the 3 wk training program. During the first and sixth training session, SEMG was recorded. To determine the effects of the HIT program on performance, subjects performed a 40 km time trial (TT40) before and after the training intervention. The frequency of SEMG is a measure of the muscle fatigue and hence was used to identify the variation of the signal properties. Three weeks of intensified training decreased the mean power frequency of the SEMG signal during the latter stages of HIT (interval seven) 50.2 ± 5.1 to 47.5 ± 4.2 Hz (P < 0.05). The preliminary conclusions of these experiments suggest that high-intensity interval training enhanced endurance performance and reduced the fatiguing of the muscles. It is suggested that this was possibly due to recruitment of addition slow-twitch motor units. PMID- 17282068 TI - Advanced measurement and quantitative appraise of anisodamine on calcium triggered in cardiac myocyte. AB - Both patch clamp and laser scanning confocal microscopy (LSCM) was applied to appraise the Anisodamine's cardioprotective effects quantitatively and its mechanism were studied. MTT measurement was observed cell viability and Fluo-3/AM was utilized for real-time free calcium with LSCM; ICa,Lexposed to Anisodamine was measured by whole-cell patch clamp recording technique. Our study observed that KCL-triggered calcium elevation could be decreased by Anisodamine at dose of 0.04mmol/L and 0.08mmol/L with the decreased value of 46.6%, 54.3% correspondingly. Further study of Anisodamine at 0.08mmol/L showed a marked inhibitory modulation of L-type Ca2+current density in a time dependent manner with decreased ratio of (34.8±7.9) % (n=6, P<0.01), from the value of -4.474 pA/pF to - 2.882 pA/pF and accelerated Vi1/2of current inactivation curve from -14.7mV to -28.4mV and delayed Vi1/2of current activation curve from -15.6mV to -9.51mV. Our result suggests that Anisodamine conferred the cardioprotection by decreasing calcium elevation quantitatively; the likely mechanism was suggested to be responsible for inhibition of L-calcium channel. PMID- 17282069 TI - Realgar Nanoparticles Induced Cytotoxicity in Promyelocytic Leukemia HL-60 Cells. AB - Realgar, one of mineral drugs in Chinese traditional medicines has attracted an increasing attention because of its prominent anti-tumor effect. However, new challenges for improving its bioavailability has to be faced. Our previous studies have demonstrated that realgar nanoparticles may provide a less toxic agent for anti-neoplasia by suppressing angiogenesis. In the present study, we improved milling process, prepared raw realgar particles and realgar nanoparticles with the same background As2O3concentrations and compared their cytoxcity to promyelocytic leukemia HL-60 cells including inhibiting cell growth, inducing oxidative stress. It was found that treatment with realgar nanoparticles resulted in considerably low cell viability compared with raw realgar particles. On the other hand, treatement with realgar nanoparticles promoted the generations of reactive oxygen species (ROS) and inhibited the activity of catalase (CAT), which was accompanied by lipid peroxidation and protein oxidation, especially the loss of its free thiols, whereas such events was not observed in HL-60 cells exposed to raw realgar particles. These results suggest that realgar nanoparticles are superior over raw realgar particles for their cytotoxicity including inhibition of cell proliferation and enhanced effects of oxidative stress, which may provide a possibility for its application in tumor therapy. PMID- 17282070 TI - A causal discovery approach to identifying active components of herbal medicine. AB - In the present study, a stepwise causal adjacent relationship discovery (STEPCARD) method has been developed to identify active components of herbal medicine. The combination of two active components had been successfully recognized from a typical Chinese formulation. Animal experiments validated the computational result. It indicates current work might be helpful to accelerate the process of new drug discovery from herbal medicine. PMID- 17282071 TI - Empirical study on modeling quantitative composition- activity relationships in chinese herbal medicine. AB - Chinese herbal medicine (CHM) consists of up to hundreds of chemical components, which have complex relationships with their bioactivities. Quantitatively modeling composition-activity relationships playing a crucial role in drug design from CHM. In this paper, principle component regression, partial least square regression and least square support vector machine were used to perform this task and exhibit high predictive precisions. PMID- 17282072 TI - Application of microdialysis technique in the traditional chinese medicine. AB - The concentration of extracellular neurotransmitters can be dynamically measured by in vivo microdialysis. This technique can apply to quantitatively evaluating the beneficial effects of Traditional Chinese Medicine (TCM). In the present study, the protective effects of Puerarin (Pur) on cerebral injuries evoked by ischemia/reperfusion was supported by a decrease of extracellular amino acids, especially glutamate (Glu), which were monitored by microdialysis combined with HPLC throughout the experiments. It suggested that, in addition to being a versatile and practical method in neuroscience, the microdialysis technique would play an important role in assessing and screening the effects of TCM. PMID- 17282073 TI - An Introduction to MAMA (Meta-Analysis of MicroArray data) System. AB - Analyzing microarray data across multiple experiments has been proven advantageous. To support this kind of analysis, we are developing a software system called MAMA (Meta-Analysis of MicroArray data). MAMA utilizes a client server architecture with a relational database on the server-side for the storage of microarray datasets collected from various resources. The client-side is an application running on the end user's computer that allows the user to manipulate microarray data and analytical results locally. MAMA implementation will integrate several analytical methods, including meta-analysis within an open source framework offering other developers the flexibility to plug in additional statistical algorithms. PMID- 17282074 TI - A multi-objective hybrid genetic based optimization for external beam radiation. AB - A multi-objective hybrid genetic based optimization algorithm is proposed according to the multi-objective character of inverse planning. It is based on hybrid adaptive genetic algorithm, which combines the simulated annealing, uses adaptive crossover and mutation, and adopts niched tournament selection. The result of the test calculation demonstrates that excellent converge speed can be achieved using this approach. Key words- Inverse Planning Multi-objective optimization Genetic algorithm Hybrid. PMID- 17282075 TI - A Protein Classification Method Based on Latent Semantic Analysis*. AB - In this paper a new method that uses Latent Semantic Analysis (LSA) to denote a protein sequence is proposed for researching the protein classification problem. A protein is vectorized according to its content of biological words: patterns and motifs, which are generated by utilizing TEIRESIAS algorithm and MEME/MAST system respectively. More precise description vectors of proteins are obtained through employing LSA. Those vectors are used to classify proteins combined with the Support Vector Machine (SVM). Experiments of family-level protein classification on Structural Classification of Proteins database show that the performance of this method is better than that of the other state-of-the-arts methods. PMID- 17282076 TI - Ontology-based aggregation of biological pathway datasets. AB - The massive accumulation of biological data in the past decades has generated a significant amount of biological knowledge which is represented in one way as biological pathways. The existence of over 150 pathway databases reflects the diversity of the biological data and heterogeneity of data models, storage formats and access methods. To address an intriguing biological question, it is not uncommon for a biologist to query more one pathway database to acquire a more complete picture of current understanding of biology. To facility life scientists in searching biological pathway data, we designed a biological pathway aggregator which aggregates various pathway datasets via the BioPAX ontology, a community developed ontology based upon the concept of Semantic Web for integrating and exchanging biological pathway data. Our aggregator is composed of modules that retrieve the data from various sources, transform the raw data to BioPAX format, persist the converted data in the persistent data store, and enable queries by other applications. PMID- 17282077 TI - Inducing Pairwise Gene Interactions from Time-Series Data by EDA Based Bayesian Network. AB - Recently a variety of high throughput experimental techniques, such as DNA microarray, are opening system-level perspectives of living organisms on molecular level. Inferring gene-gene interactions from time series data generated from these technologies is an important computational method to help us to understand the system behavior of living organisms 1. The Bayesian Network (BN), which is a graph-based representation of a joint probability distribution that captures properties of conditional independence between variables, is a desirable tool. However, how to construct appropriate BNs that best fit the data profile is very difficult since the number of BNs on nvariables is the super-exponential of n. To avert the combinational explosion, in this paper, we use Estimation of Distribution Algorithms (EDAs) to search the space. Also, in order to generate meaningful individuals, we also propose depth-first search method to cut circles in the graphs. We have tested our method on cell-cycle gene expression data and found that it can not only discover some existing relationships in other literatures and Gene Ontology, but also reveal some previously unknown interactions. PMID- 17282078 TI - Prediction of domain interactive motif pairs. AB - Protein domain-domain interaction pairs supply functional information about the interacting proteins; and finding interaction motif pairs in protein-protein interaction database can deeply disclose the essence of the protein interaction. Up to now, there is little research work on prediction of interaction motif pairs within domain-domain interaction pairs. In this paper, we propose a new method to predict domain interaction motif pairs. We start from collecting contact segment pairs in the PDB protein complexes, and then use the contact segment pairs as seeds to iteratively cluster the protein-protein interaction database with the help of functional domains, finally we generalize the similar segment pair clusters to produce motif pairs. Using our method, we find 528 motif pairs. PMID- 17282079 TI - Experimental Study of Radiation Efficiency from an Ingested Source inside a Human Body Model*. AB - The attenuation of human body trunk at frequency range of 100MHz to 6GHz from an internal source was estimated using a simplified experimental model. Antennas were placed in the model which was filled with distilled water, 0.9% NaCl saline solution, and porcine body tissue alternately to determine the attenuation of the system. Saline has greater attenuation than water due to its higher conductivity, while porcine body tissue has attenuation bounded by saline solution and water. Estimated attenuation at the four ISM bands, 434MHz, 915MHz, 2.45GHz and 5.8GHz were given and all of these bands satisfied the safety and sensitivity requirements of a biomedical telemetry system. 915MHz and 2.45GHz are good choices for the wireless link because of their relatively larger electrical size of RF components such as antenna. In addition, with the growth in wireless LAN and Bluetooth technology, miniaturized antennas, camera modules, and other RF devices have been developed which can be employed in biomedical ingested or implanted devices. This paper gives a reference of attenuation values of a human body trunk of average size. It should be noted that the attenuation values can be different for different body size and different body composition, and therefore the values in this paper serves as a reference only. PMID- 17282080 TI - The acquisition hardware system with direct digital synthesis and filtered back projection imaging in electrical impedance tomography. AB - Electrical impedance tomography is a new imaging modality that produces images by computing electrical conductivity within the body. This paper presents a basic acquisition hardware system of Electrical Impedance Tomography with direct digital synthesis (DDS), which is used for studying the human head electrical property. The filtered back-projection algorithm is used for image reconstruction. PMID- 17282081 TI - The Multifocal ERG in Early Detection of Diabetic Retinopathy. AB - To assess retinal changes in diabetic eyes at early stage of retinopathy, retinal responses were examined using multifocal ERG. Seven healthy subjects, 16 diabetics with no apparent retinopathy (NDR) and 9 diabetics who had background diabetic retinopathy (BDR) underwent multifocal ERG testing. The first slice of the second order kernel (K21) were extracted from multifocal ERG record and summed. Three major peaks (P1, N1 and P2) on the trace of summed K21 are evaluated across all subjects. With their amplitude and implicit time as 6 features, linear classifiers were built. These classifiers were used to discriminate eyes of control, NDR and BDR subjects. The classification error dropped significiantly. PMID- 17282082 TI - Artificial neural network-based estimation of the eyeball position using the magnetic contact lens sensing technique. AB - We have created an artificial neural network based approach for measuring eye movement using a magnetic contact lens sensing technique. The sensor array is based on using four magnetoresistive sensors. A two-layer feed-forward artificial neural network was used and an artificial eyeball model was made for the test. The neural network is trained with sample data obtained from nine spots. After training, we compared the position calculated from the developed system with the real one. The result shows that there is a good linear relationship between them. This indicates the developed system is capable of recording the position of the eyeball with a high degree of accuracy. PMID- 17282083 TI - Lung Impedance Contributions to the Total Impedance based on a FDM Model and Lead Field Theory. AB - Predicting tissue resistivity is of significance in medical diagnosis due to the fact that disease induces related tissue resistivity change. Studies have shown that the lung and tissues tumors reflect significant impedance change with disease states. It is hypothesized that the impedance measurement with the largest contribution from the organ of interest will result in less error. In this paper, we determined the percentage contribution of the lung impedance to the total impedance for five different external electrode configurations using a high resolution finite difference model (FDM) of the thorax along with lead field theory. The electrode combinations showed a contribution by the lungs of approximately 20% of the total impedance. Many configurations showed contributions of 15%. The results also showed that each lung could be isolated from the opposite lung. PMID- 17282085 TI - Welcome Message from President of IEEE-EMBS. PMID- 17282084 TI - Steady State Condition in the Measurement of VO2and VCO2by Indirect Calorimetry. AB - Resting Metabolic Rate (RMR) is computed using VO2and VCO2short time 15-minute window measurement with Indirect Calorimetry (IC) instruments designed with mixing chamber. Steady state condition using a 10% variation coefficient criteria is the main objective to achieve metabolic long time prediction reliability. This study address how susceptible is the steady state VO2, VCO2measurement condition to the clino orthostatic physiological maneuver. 30 young healthy subjects were analyzed. Only 18 passed the 10% variation coefficient inclusive criteria. They were exposed to 10 minutes clino-stage and 10 minutes orthostage. The hypothesis tests show not statistical significance (p< 0.1) in the average and variance analysis. It is concluded that the steady state is not influenced by the patient position IC test, probably because IC mixing chamber instruments are insensitive to detect a mayor physiological dynamics changes that can modify the steady state definition. PMID- 17282087 TI - Exhibit fair directory. PMID- 17282086 TI - Invited conference keynote speaker. PMID- 17282088 TI - Technical program highlights. PMID- 17282090 TI - Medical engineering & physics. PMID- 17282091 TI - Editor's Notes. PMID- 17282093 TI - Conference committee. PMID- 17282094 TI - Program index. PMID- 17282096 TI - Introduction to IEEE-EMBS -- What Can the Society Do for You? AB - IEEE-EMBS is the largest bioengineering society in the world. This paper introduces material about the Society and its benefits, including the EMBS mission, types of EMBS membership, and direct membership benefits such as the EMB Magazine. EMBS governance is also explained, including the new worldwide representational organization for AdCom (Administrative Committee), and recent changes in the Executive Committee. EMBS delegates to other societies are described, as well as the infrastructure of the main office and duties of key personnel there. Infostructure efforts related to the website and web-based conference registration and manuscript submission are also briefly discussed. Publications sponsored and co-sponsored by EMBS are reviewed. Plans for future national conferences are put forth. The various EMBS awards are outlined. Context is provided for the relationship between IEEE and EMBS, and a brief description is provided of IEEE organization and benefits. PMID- 17282095 TI - IEEE Engineering in Medicine & Biology Society Award Recipients 2005. PMID- 17282097 TI - Virtual modelling of compartmental pharmacokinetic systems. AB - This paper presents an analysis of different methodologies for modelling pharmacokinetic systems under the context of a telemedicine system oriented to the on-line and personalized knowledge generation. We use a simplified 3-pool kinetic system for a better clarification of several relevant modelling formalisms. A more complete 3-pool urea kinetic model is built simply connecting EL components pertaining to a pharmacokinetic library previously developed. The evolution of the urea concentration during the dialysis of a patient provided by this model was compared successfully to the evolution computed by a 2-pool model experimentally validated. The 3-pool model provides more information regarding the interstice and a high capacity to be modified for attending to the knowledge needs of physicians, as well as biomedicine advances. As a major conclusion, our outcomes suggest that virtual modelling is an excellent methodology in biomedical engineering to support the on-line generation of personalized health knowledge for telemedicine systems. This is due to its capacity for reusing components at horizontal and vertical level, and for implementing multiformalism and multidomain models, what simplifies the task to represent complex physiological and artificial systems. PMID- 17282098 TI - Finite element modeling and simulating of accommodating human crystalline lens. AB - In this paper an axisymmetrical, linear, finite element model of human crystalline lens and zonules is constructed to simulate the accommodation process of the lens, based on the published experimental data. Some detailed modeling procedure and data processing differ from previous studies. Our results show that the optical power increases when ciliary body moves away from the lens. The outcome of this paper proves that numerical modeling is a useful and effective method in the study of accommodation. PMID- 17282099 TI - Dynamic model of the aqueous humor circulation with application to simulation of the treatment for primary open angle glaucoma. AB - In order to study the mechanism of the aqueous humor circulation and its relationship to the glaucoma macroscopically with engineering methods, a dynamistic model was presented, which can be used to simulate the situation and the treatment of the primary open angle glaucoma (POAG). The frame of the model was built based on the ophthalmically accepted feedback mechanism between the aqueous humor circulation and the intraocular pressure (IOP). The transfer functions and the parameters were educed from the analysis of physiological theories, the basic elements of hydrodynamics, and the clinical parameters. The relation between the parameters of the system and the episode mechanism of POAG was discussed. A digital method was used to simulate the Challenge test and some medicines' treatment of POAG, and the results were consistent with clinical observations. The results illuminate that the model can simulate the mechanism of the aqueous circulation and the curative mechanism of some medicines under the pathological condition of the POAG. Additionally, a few parameters which can hardly be captured with clinical method could be obtained from the model. These parameters can be helpful for the diagnosis and prediction of the curative effect. PMID- 17282100 TI - Influence of muscle cooling on the passive mechanical properties of the human gastrocnemius muscle. AB - The purpose of the present study was to examine the influence of muscle cooling on the passive mechanical properties of the human gastrocnemius muscle (GAS) in vivo. In a thermoneutral (a room temperature of 18-23°C) and a local cooling (placing the right lower leg into cold water with a temperature of 5-8°C for 60 min) conditions, the change in passive plantarflexion force (F), which is produced only by the GAS length change, was taken in five subjects during passive knee extension from 90° to 0° with a constant ankle joint angle of 10° dorsiflexion. To evaluate an elastic component of the passive plantarflexion force of GAS, the subject held full knee extended position for 1 min (i.e. relaxation period). Skin and muscle temperature of GAS were also measured using a core temperature thermistor. The peak value of F (Fve) that was measured at the end of the knee extension phase, the decrease of F (ΔF) during the relaxation period, and the F at the end of the relaxation period (Fe) were measured in the two conditions. Muscle cooling decreased the skin and muscle temperature by 6.7 ± 1.1°C and 8.1 ± 2.5°C, respectively. Fve increased by 24% ± 22% by muscle cooling. ΔF in the thermoneutral and local cooling conditions were 11.5 ± 4.9 N and 12.5 ± 2.9 N, respectively. Fe increased by 28% ± 21% by muscle cooling. PMID- 17282101 TI - Identification of Linear Time Varying Systems using Basis Pursuit. AB - System identification involves creating mathematical models of systems using measurements of their inputs and outputs. Linear time-varying systems form an important sub-class of models that require the use of specialized system identification techniques. One such approach involves expanding the time-varying parameters onto a set of temporal basis functions and then estimating the resulting expansion coefficients. This, however, requires the estimation of a large number of parameters and often results in extreme noise sensitivity. In this paper a novel algorithm for identifying time-varying systems is presented. It combines a temporal expansion with a term selection step that uses the "Least Absolute Shrinkage and Selection Operator", or Lasso. The Lasso term selection technique constructs a model structure with a nearly minimal number of non-zero terms, and hence with relatively low estimation variances. The algorithm is demonstrated by using it to detect changes in the dynamic stiffness of the human elbow immediately following the onset of a broadband perturbation. PMID- 17282102 TI - Modelling for computer controlled neuromuscular blockade. AB - In this paper we present data collection and methods for the selection of a model class with the goal of automated neuromuscular blockade (NMB). Neuromuscular response was measured in the presence of rocuronium in rabbits (N=5) and humans (N=14). An average response was formed and used to determine optimal ARX and Laguerre representations for a wide range of orders and parameters. A 6th order Laguerre model was selected based on its accuracy and simplicity. Models were identified for each subject. For each group, variation was measured by comparison to the average response. The standard deviation of the average impulse response static gain was 45.4 and 45.8% of the mean for the rabbit and human models, respectively. The range of static gain was 121 and 159% of the mean for the rabbit and human datasets. Frequency domain analysis showed differences in gain of 12 and 15dB, and phase of 45 and 75° for the rabbit and human models respectively. With this knowledge, design and development of appropriate controllers for NMB will proceed. PMID- 17282103 TI - WaveShrink Using Modified Hyper-Shrinkage Function. AB - WaveShrink plays pivotal role in analysis of complex bio signals. Wavelet analysis and WaveShrink are the established techniques of statistical research which have to be blended with the analysis of bio signals to provide a high degree of correlation between the desired signal and the observed signal. The multifaceted shrinkage function will obtain lurid responses to the signal perturbed to a very high degree by intransigent noise functions. It might be impossible to efface noise but its possible to ameliorate the recovery of the desired signal. Here we have obtained computationally efficient formula for computing the exact bias, variance, mean and risk. The former is the essence of any shrinkage function but latter is the essence of our paper. The purpose of our shrinkage function is to assuage the recovered signal to uphold our procedure for signal denoising and non-parametric regression. Our shrinkage function enjoys the same asymptotic convergence rate as the rest but offers obdurate resistance to pernicious factors disturbing the desired signal of interest. PMID- 17282104 TI - Effective Approach for Detecting the Single Trial ERP Using Rational Gaussian Neural Network. AB - A novel approach is proposed to deal with the problem of detecting the single trial ERP using a modified RBF neural network, rational Gaussian network. The Gaussian RBF is normalized to obtain optimal behavior of noise suppression even at low SNR. The performance of the proposed scheme is also evaluated with both MSE and the tracking ability. Several experimental results with real ERP signals provide the convergent evidence to show that the presented method can significantly enhance the SNR and successfully track the variation of the signal such as the specified ERP in the applications of biomedical signal processing. PMID- 17282105 TI - Novel method for measuring the complexity of schizophrenic EEG based on symbolic entropy analysis. AB - Symbolic dynamics is a useful tool in several fields of complexity analysis in nonlinear science. In order to investigate complexities of the human brain electrical activities under different brain functional states, a novel method in terms of symbolic entropy is defined and proposed in this paper. The novel algorithm based on symbolic dynamics is developed for quantitatively measuring the complexity of the EEG data. Simulated signals derived from chaotic systems and several real EEG data under normal and pathological brain functional states are examined and compared. The experimental results show that the proposed method can distinguish not only the complexities of simulated signals but also the complexities of two groups of EEG data under different brain functional states. It is superior to the traditional entropy methods. Moreover, the algorithm can be easily completed and fast computed. PMID- 17282106 TI - An Improved Pre-processing Approach for Photoplethysmographic Signal. AB - Heart rate variability and motion artifact are two major obstacles to the Photoplethysmographic (PPG) signal analysis, which is a very promising tool to derive useful information about the hemodynamics as well as autonomic nerve system. This paper suggests employing a truncation/extrapolation method on the PPG signal or its first order derivative to overcome the heart rate variability problem while extract a refined mean PPG pulse waveform. Meanwhile, the cross correlation detection method is employed to remove the motion artifacts. Test results indicate that the proposed approach can effectively enhance the signal to noise ratio of PPG waveform and therefore verify the effectiveness of the proposed preprocessing scheme. PMID- 17282107 TI - Phase Coordination between Intracranial Pressure and Electrocardiogram Signals. AB - Methodologies of deriving phase information from pulsatile intracranial pressure (ICP) signal and characterizing its phase coordination with electrocardiogram (ECG) signal were discussed. The application of ICP phase characterization methods to data from several clinical contexts showed that 1) Unstable periods of ICP were associated with a decreased ICP phase coordination with ECG; 2) Surgical treatment of Chiari malformation patients caused an increase of phase coordination; 3) Changes of cerebral vascular tone could also lead to changes of ICP and cerebral blood flow velocity phases relative to arterial blood pressure. The results of our analysis could shed some light on a new tuned-oscillator theory of intracranial pulsatile dynamics as well as support phase characterization of signals as a new way of extracting clinically useful information from ICP and cerebral hemodynamic measurements. PMID- 17282108 TI - A Comparative Study on Microcalcification Detection Methods with Posterior Probability Estimation based on Gaussian Mixture Models. AB - Automatic detection of microcalcifications in mammograms constitutes a helpful tool in breast cancer diagnosis. Radiologist's confidence level on microcalcification detection would be improved if a probability estimate of its presence could be obtained from computer-aided diagnosis. In this paper we explore detection performance of a simple Bayesian classifier based on Gaussian mixture probability density functions (pdf). Posterior probability of microcalcification presence may be estimated from the probabilistic model. Two model selection algorithms have been tested, one based on the Minimum Message Length criterion and the other on discriminative criteria obtained from the classifier performance. In addition, we propose a complementing model selection algorithm in order to improve the initial system performance obtained with these methods. Simulation results show that our model gets a good compromise between classification performance and probability estimation accuracy. PMID- 17282109 TI - A model for charged molecule transport in the interstitial space. AB - The extravascular matrix is believed to carry negative charge due to its glycosaminoglycans (GAGs) composition. In the present study, we developed an electrodiffusion-convection model to investigate the mechanisms by which this negative charge affects the charged molecule transport through the interstitial space. The model predictions demonstrate that the apparent tissue diffusion coefficient of negatively charged albumin (net charge = -19) in rat mesentery should be comparable to that of neutral dextran with equivalent hydrodynamic radius. The discrepancy in their concentration distributions in the mesenteric tissue, which was observed by Fox and Wayland [1], may be explained by the charge effect of the tissue matrix, especially by the partitioning between the vascular and extravascular compartments, instead of different apparent diffusion coefficients. The charge effect induces equivalent to about two-fold difference in apparent tissue diffusion coefficients of charged albumin and neutral dextran with same free diffusion coefficients. Furthermore, our results indicate that the more negative charge the interstitium has, the smaller the interstitial fluid flow is when the same tissue-lymph pressure gradient is applied. PMID- 17282110 TI - Analyzing effects of sodium pentobarbital on hemodynamic responses by using a graphic control system. AB - The maintenance of adequate anesthesia is very important for animal studies. This goal could be achieved if the pharmacokinetics of the anesthetic is known and a well-controlled instrument system is used. To this end, a graphic control system is developed to study the effects of sodium pentobarbital on anesthesia. Hemodynamic signals such as mean blood pressure, pulse pressure, heart rate were analyzed and used as index for quantitative evaluating the level of anesthesia. Factors that could affect the anesthesia, e.g. body weight (BW) of the rat and the concentration of pentobarbital were used as independent variables to examine the survival time (dependent variable) for an overdosage anesthesia. The relationship among the BW, the drug concentration, and the survival time before death were formulated. As most physiological system have shown, the empirical relationship is exponential in nature. This implies that the mechanism is highly nonlinear and it is complicated by the buffering characteristics of life. Hence, a precision feedback control system seems to be necessary for a well-controlled anesthesia. PMID- 17282111 TI - Analysis of ICG Pharmacokinetics in Cancerous Tumors using NIR Optical Methods. AB - In this paper, we present three different compartmental models to model the pharmacokinetics of Indocyanine green (ICG) in cancerous tumors. We introduce a systematic and robust method to analyze ICG pharmacokinetics based on extended Kalman filtering (EKF) framework. We introduced information theoretic criteria for best compartmental model selection in terms of statistical fit. We tested our approach using the ICG concentration data acquired from four Fischer rats carrying adenocarcinoma tumor cells collected using near infrared (NIR) techniques. Our study indicates that, in addition to the pharmacokinetic rates and ICG concentrations in different compartments, EKF model may provide parameters that may be useful for cancerous tumor differentiation. PMID- 17282112 TI - A Novel PBPK/PD Model with Automatic Nervous System in Anesthesia. AB - In terms of the characteristic of anesthetic operation, this paper propose new Physiologically Based Pharmacokinetics / Pharmacodynamics (PBPK/PD) model that focus on the important role of Autonomic Nervous System (ANS) more. Automatic nervous system that is divided into the sympathetic nervous system and the parasympathetic nervous system, at the same time, is the important target of drug effect in anesthesia. Consequently, Not only does the action levels of Automatic Nervous System indicator the Anesthesia State, but feed back altering the physiological state parameters of pharmacokinetics, which being one crucial reason of time-variant and nonlinear drug effect. However, the recent PBPK modeling and simulation strategy only estimate specific absorption, distribution, metabolism and excretion (ADME) parameters but consider no modulation result of Automatic Nervous System any longer. So far, in order to avoid over-interpreted data from mathematical models and to take more consideration of clinical significance, the PBPK/PD model with Automatic Nervous System presented is helpful to make clearer relationship between PK and PD, that between sophisticated of model and real physiological phenomenon in Anesthesia than before. PMID- 17282113 TI - Role of sphingosine kinase in the expression of adhesion molecules on monocytes induced by tumor necrosis factor-alpha (relevant to atherosclerosis). AB - TNFα stimulates SPHK in the monocyte, which leads to the expression of adhesion molecules on the cell surface. The adhesion of leukocytes to the endothelium is one of the early stages of the onset of atherosclerosis. In this paper, we have delineated the TNFα-induced and SPHK-dependent signaling pathway. In addition, we have developed a biomathematical model to qualify the SPHK time-dependent activity at a specific site in the cell upon TNFα stimulation. Thus, this study provides a biochemical and mechanistic approaches to the understanding of leukocyte-endothelial attachment, so that measures could be designed to minimize the onset of atherosclerosis. PMID- 17282114 TI - On-line estimation of propofol pharmacodynamic parameters. AB - A novel advisory system, the Anesthesia Advisory Display (AAD) has been recently developed. It displays information about actual and future predictions of anesthetic drug concentrations mapped to clinical end-points such as BIS, basing on the actual infusion rate combined with population pharmacokinetic and interaction pharmacodynamic (PKPD) models. According to the large variability observed among patients in clinical end-points to the same dosing history, a population model could fail in predicting the real patient's behavior: an "individualized" model is then necessary. An on-line estimation of the model's parameter for the single patients has been developed, basing on the extended Kalman filter algorithm. The method has been tested on data of 40 patients from a previous clinical study and the prediction of the individual models have been compared with the population model's. PMID- 17282115 TI - Investigation on biomedical engineering education of the universities in US and UK. AB - To enhance the student training and scientific research of biomedical engineering (BME) department of Tsinghua University, we investigated the top three universities on BME in US, which are John Hopkins University (JHU), Georgia Tech and Emory University (GTEU) and the Harvard & MIT Division of Health Science and Technology (HST). We also investigated the department of medical physics and bioengineering of University College London (UCL) in UK. According to the investigations, many useful experiences are obtained. In this paper, the following four aspects are specified: first, the research fields being concerned in biomedical engineering in the above universities; second, the characteristics of the training programs to the undergraduate and graduate students of BME in these universities; third, the experiences of these universities; fourth, the suggestions to us. PMID- 17282116 TI - Construction of a knowledge center for medical image processing. AB - This article introduces a medical imaging and image processing knowledge center which serves as an e-learning platform based on network technology. This platform includes contents of medical imaging and medical image processing for the teaching activities, virtual reality tutoring system of human skeleton, medical image database, etc. The purpose of establishing this platform is to recruit and excavate information records which usually associated with the daily data exchanged in teaching and research activities. Then it will gradually form an open professional knowledge database. At present, this platform plays the role of knowledge community in the educational activities of BME program in Tsinghua University. PMID- 17282117 TI - BME Education 5 Years at Zhejiang University. AB - Biomedical engineering (BME) is a developing interdisciplinary subject derived from the combination of modern life science, medical science and engineering. In this paper, the development of BME education during the past five years in Zhejiang University has been presented, especially some effective and innovative acts, such as modularizing curriculum, establishing the common platform for the undergraduates□experiment and practice, setting up student research train program (SRTP), etc. All these acts have been carried into execution in the process of education and training of undergraduates. PMID- 17282118 TI - On talent training of medical equipment in biomedical engineering field. AB - In this paper, the industrial scale, developing trend and the need of talent training in the field of medical instrument is analyzed, the drawbacks in four year-university education of our biomedical engineering in China are pointed out, and the status quo of professional education of medical instrument in China is introduced. PMID- 17282119 TI - Biomedical imaging and image processing course in shanghai jiao tong university. AB - The biomedical imaging and image processing course in Shanghai Jiao Tong University is a core course in the Department of Biomedical Engineering. We have taken many measures in the course system, student practice, classroom teaching, and active and creative learning. The effectiveness of the measures and the results are reported. The course is highly appraised by teachers and students and won many awards. The measures and experience of our course may enrich the teaching and learning method bank in Biomedical Engineering (BME) education. PMID- 17282120 TI - A robot-assisted orthopedic telesurgery system. AB - A robot-assisted orthopedic telesurgery system, named HIT-RAOTS, has been developed according to Chinese conventional operation method. Its main function includes obtaining images with information of position and orientation of fracture, providing fracture information for doctors, assisting the doctors to complete the reposition of fracture and locking operation of intramedullary nail. In this system, a 6-dof force-reflecting master device, with a pantographic parallelogram mechanisms driven by harmonic DC servomotors, is used to control the slave manipulator movement and to translate the force from the operating room to the surgeon console; A slave robot system integrated a 6-dof force sensor, with a parallel manipulator actuated by six AC servomotors, is applied for the accurate repositioning; A virtual simulation system and human-machine interface are also developed. PI controller based on local network is used to realize the teleoperation. Only little irradiation is issued during the reposition. It can assist surgeons to perform bone-setting more safely by reducing irradiation damage to both surgeries and patients, more easily by releasing the surgeons from the heavy operation and more perfect by improving accuracy of reposition. PMID- 17282121 TI - Vital signs monitoring and patient tracking over a wireless network. AB - Patients at a disaster scene can greatly benefit from technologies that continuously monitor their vital status and track their locations until they are admitted to the hospital. We have designed and developed a real-time patient monitoring system that integrates vital signs sensors, location sensors, ad-hoc networking, electronic patient records, and web portal technology to allow remote monitoring of patient status. This system shall facilitate communication between providers at the disaster scene, medical professionals at local hospitals, and specialists available for consultation from distant facilities. PMID- 17282122 TI - Towards the design of a generic systems architecture for remote patient monitoring. AB - Remote patient monitoring (RPM) of vital signs offers the potential to provide high quality care to elderly and chronically ill people in their home environment, while making effective use of healthcare resources. However, among other factors, the lack of technical, clinical and organisational interoperability of RPM systems has hindered integration into mainstream healthcare. This research offers work towards defining stakeholders and their requirements for the design of a generic systems architecture that fits various types of remote patient monitoring and can be deployed in different healthcare systems. Requirements are specified not only for technical compatibility with other systems, but also for clinical and organizational compatibility with healthcare professionals' routines and power structures. PMID- 17282123 TI - ECG Parameter Extractor of Intelligent Home Healthcare Embedded System. AB - Automatic ECG QRS complex detection has been widely studied and used over the past decade. Although QRS complex is the most prominent feature in ECG and can provide useful information about the heart status, other parts of the ECG (P wave, T-wave, etc) are also significant in determining the health status. Recently, researches for P-wave and T-wave detection algorithms started to appear but a parameter extractor in obtaining most essential ECG parameters (PQRST) is still not very popular. Considering that all these can be integrated together, we propose an Intelligent Home Health Care Embedded System (IHHCS) with essential ECG parameters extraction that can provide diagnosis about health status of patients directly at home. Inconvenient visits and precious time spent in health checking at hospitals or clinics can be saved. PMID- 17282124 TI - The research of telemedicine system based on embedded computer. AB - In this study a telemedicine system based on embedded computer system is presented, which is designed specially for the need of immediate medical treatment in remote areas. In the system embedded Linux is cut down, customized and ported into the monitor terminal. Data interchange between the monitor center and the terminal via Internet and GPRS is introduced. This system which is convenient, portable and high cost-effective, can tele-monitor four vital bio signals, such as cardiograph, blood pressure, respiration and temperature through GPRS or Internet, which is of great improvement for development of telemedicine in developing countries. PMID- 17282126 TI - The Effects of Heptanol on Electrical Coupling during Ischemia in the Perfused Isolated Rat Heart. AB - The aims of the present study were to examine the effect of heptanol on electrical coupling during ischemia, and to assess whether changes in electrical coupling by heptanol is associated with its cardiac protection. Perfused isolated rat hearts were subjected to a 24 min infusion of heptanol (0.05, 0.1, 0.5 or 1.0 mmol/L) followed by 70 min of global no-flow ischemia or by 20 min of regional ischemia and 60 min of reperfusion. Heptanol markedly decreased arrhythmia scores during ischemia and reperfusion as well as reduced infarct size to a degree similar to that induced by ischemic preconditioning. In the prolonged ischemia model, heptanol delayed the onset of uncoupling, increased time to plateau, and decreased the maximal rate of uncoupling during ischemia. Ischemic preconditioning had similar effects on these parameters. These results demonstrate that treatment with the gap junction uncoupler heptanol confers cardioprotection against ischemia, and this effect is related to delayed electrical uncoupling during prolonged ischemia. PMID- 17282125 TI - Impulse initiation and conduction in the murine atria: a basis for future investigation of sinus node dysfunction. AB - The prevalence of atrial conduction defects and sinus node dysfunction increases with age. These age-related changes may play a critical role in establishing the substrate for the development of atrial fibrillation (AF), the most common sustained arrhythmia. Despite the association between atrial arrhythmias and age, little is known of the mechanisms that underlie changes in atrial electrophysiological function. Ongoing studies in our laboratory are focused on determining the mechanisms of atrial conduction defects associated with aging and disease. The purpose of this report is to present some initial studies of the murine sinus node and the approach we have taken to quantify conduction at the site of impulse initiation. PMID- 17282127 TI - The Effects of κ-Opioid Receptor Stimulation on Electrical Coupling during Ischemia in the Perfused Isolated Rat Heart. AB - Two series of experiments were performed in the perfused isolated rat heart to determine whether stimulation of κ-opioid receptor with U50,488H, a selective κ-opioid receptor agonist, produces any changes in electrical coupling during prolonged ischemia and whether these changes in electrical coupling is associated with the cardioprotection induced by U50,488H. It was found that U50,488H concentration dependently increased formazan content and reduced lactate dehydrogenase (LDH) release induced by 30 min of ischemia and 120 min of reperfusion, and the ameliorating effect of 10-5mol/L U50,488H was abolished by 5x10-6mol/L nor-binaltorphimine (nor-BNI), a selective Κ-opioid receptor antagonist, or 10-4mol/L 5 hydroxydecanoate (5-HD), a selective mitochondrial ATP-sensitive K+(KATP) channels blocker. The onset of electrical uncoupling during prolonged ischemia was delayed by U50,488H, and delaying effect was not only abolished, but also advanced by nor-BNI or 5-HD compared with control group. These results demonstrate that delayed electrical uncoupling is associated with the cardioprotection induced by U50,488H. These effects of U50,488H are mediated by mitochondrial KATPchannels. PMID- 17282128 TI - Simulating cardiac ventricular action potentials in rat and mouse. AB - We have developed a computational model for the rat cardiac ventricular cell by using electrophysiology data. Our control model (Pandit et al., 2001). The model represents the bioelectric activity in the left ventricular cells in adult male rats. We have described the differences in the membrane properties within the left ventricle to simulate the action potential variations of the endocardial and epicardial cells. We also developed a right ventricular cell model from our control model (the left ventricular cell model) to study ionic mechanisms in diabetic rats (Pandit et al., 2003) Our right ventricular cell model was also the template for us to develop a mouse ventricular cell model by using experimental data. The simulation studies in our models of the rat and mouse ventricular cells conclude that (1) the action potential changes in the left and right ventricles of the normal, diabetic, aged or spontaneously hypertensive rats is mainly due to differences in the 4AP sensitive, Ca2+independent transient outward K+current (It) current, and (2) the presence of the 4AP sensitive, slowly inactivating, delayed rectifier K+current (IKslow) in mouse is one of the main factors contributing to the faster rate of repolarization seen in mouse compared to rats. PMID- 17282129 TI - Qualitative support for the gradient model of cardiac pacemaker heterogeneity. AB - In this study, we investigate the role of sinoatrial node (SAN) cellular heterogeneity in normal cardiac pacemaker function. Using detailed ionic models of electrical activity in SAN and atrial myocytes, we have formulated a number of models of SAN heterogeneity based on discrete-region (in which central and peripheral SAN type cell are separated into discrete regions), gradient and mosaic models of SAN organisation. Simulations of each of the different models were performed in one and two dimensions in the presence of both uniform and linearly increasing conductivity profiles. Simulation results suggest that the gradient model, in which cells display a smooth variation in membrane properties from the center to the periphery of the SAN, best reproduces action potential waveshapes and a site of earliest activation consistent with experimental observations in the intact SAN. We therefore propose that the gradient model of SAN heterogeneity represents the most plausible model of SAN organisation. PMID- 17282131 TI - Multiresolution bayesian detection of multiunit extracellular spike waveforms in multichannel neuronal recordings. AB - We describe multiresolution Bayesian tests for spike detection in multielectrode recordings. We derive results for single channel and multi electrode data, and show that the use of the array model substantially improves the detection performance. The effect of signal and noise spatial correlation characteristics is also discussed. Our approach focuses on blind signal detection without any assumptions about the underlying signal parameters. It is therefore suitable for chronic recordings with electrode arrays where typically temporal and spatial nonstationarity of the extracellular waveforms complicates the estimation of the true action potential. PMID- 17282130 TI - Stability of Cardiac Action Potential Duration under Periodic Pacing. AB - Action potential duration (APD) alternans is believed to be a loss of stability and contributes much to the reentry arrhythmias. The purpose of this study is to analyze the stability conditions for one-dimension model and higher dimension model. These criterions are concluded by linear stability analysis in nonlinear dynamics. They should be useful for finding of cardiac control algorithms in low energy defibrillation and the designing of antiarrhythmic drug. PMID- 17282132 TI - Optimal rate filters for biomedical point processes. AB - Rate filters are used to estimate the mean event rate of many biomedical signals that can be modeled as point processes. Historically these filters have been designed using principles from two distinct fields. Signal processing principles are used to optimize the filter's frequency response. Kernel estimation principles are typically used to optimize the asymptotic statistical properties. This paper describes a design methodology that combines these principles from both fields to optimize the frequency response subject to constraints on the filter's order, symmetry, time-domain ripple, DC gain, and minimum impulse response. Initial results suggest that time-domain ripple and a negative impulse response are necessary to design a filter with a reasonable frequency response. This suggests that some of the common assumptions about the properties of rate filters should be reconsidered. PMID- 17282133 TI - Inferring attentional state and kinematics from motor cortical firing rates. AB - Recent methods for motor cortical decoding have demonstrated relatively accurate reconstructions of hand trajectory from small populations of neurons in primary motor cortex. Decoding results are often reported only for periods when the subject is attending to the task. In a neural prosthetic interface, however, the subject must be able to switch between controlling a device or performing other mental functions. In this work we demonstrate a method for detecting whether or not a subject is attending to a motor control task. Using the firing activity of the same neural population used for decoding hand kinematics we demonstrate that a Fisher linear discriminant performs well in classifying the attentional state of a monkey. We use the output of this classifier to augment a hidden state in a first order Markov model and use particle filtering to recursively infer hand kinematics and attentional state conditioned on neural firing rates. We demonstrate high accuracy on test data where a monkey switches between attending to a task and not. By decoding a discrete "state" in addition to hand kinematics our proposed classification and estimation scheme may enable real-world neuroprosthetic functions such as "hold", "click", and "turn off/on". PMID- 17282134 TI - Automated prediction of epileptic seizures in rats with recurrence quantification analysis. AB - The prediction of epileptic seizures is a very important issue in the neural engineering. This is because it may improve the life quality of the patients who are suffering from uncontrolled epilepsy. In our earlier work, we found that the dynamical characteristics of EEG data with recurrence quantification analysis (RQA), also called complexity measure, can identify the differences among inter ictal, pre-ictal and ictal phases. In this paper, we propose an automated technique with complexity measure of EEG recording to detect pre-ictal phase. Using the EEG recorded from rats with experimentally induced generalized epilepsy, it is found the method can detect the complexity changes of the neural activity prior to epileptic seizures. We suggest that the new method could be considered as an alternative of epileptic seizures prediction in practice. PMID- 17282135 TI - ICA Denoising for Event-Related fMRI Studies. AB - The poor SNR of fMRI data requires that many repetitive trials be performed during an event-related experiment to obtain statistically significant levels of inferred brain activity. This is costly in terms of scanner time, necessitates that subjects perform the behavioural task(s) for long durations which may induce fatigue, and vastly increases the amount of data generated. In this paper, we present a method to enhance the statistical effect size using ICA, so that the same level of significance can be obtained with shorter scanning times. We perform ICA on fMRI data from a simple event-related motor task by projecting the original data onto the linear subspace defined by the task-related ICA components. This essentially denoises the signal and results in significant improvement in the effect size. Using simulations we demonstrate that the proposed ICA-denoising procedure is robust to a variety of realistic noise models and enhances the performance of least squares estimates of the evoked hemodynamic response. PMID- 17282136 TI - Ensuring Patient Safety by using Colored Petri Net Simulation in the Design of Heterogeneous, Multi-Vendor, Integrated, Life-Critical Wireless (802.x) Patient Care Device Networks. AB - Hospitals and manufacturers are designing and deploying the IEEE 802.x wireless technologies in medical devices to promote patient mobility and flexible facility use. There is little information, however, on the reliability or ultimate safety of connecting multiple wireless life-critical medical devices from multiple vendors using commercial 802.11a, 802.11b, 802.11g or pre-802.11n devices. It is believed that 802.11-type devices can introduce unintended life-threatening risks unless delivery of critical patient alarms to central monitoring systems and/or clinical personnel is assured by proper use of 802.11e Quality of Service (QoS) methods. Petri net tools can be used to simulate all possible states and transitions between devices and/or systems in a wireless device network, and can identify failure modes in advance. Colored Petri Net (CPN) tools are ideal, in fact, as they allow tracking and controlling each message in a network based on pre-selected criteria. This paper describes a research project using CPN to simulate and validate alarm integrity in a small multi-modality wireless patient monitoring system. A 20-monitor wireless patient monitoring network is created in two versions: one with non-prioritized 802.x CSM protocols and the second with simulated Quality of Service (QoS) capabilities similar to 802.11e (i.e., the second network allows message priority management.) In the standard 802.x network, dangerous heart arrhythmia and pulse oximetry alarms could not be reliably and rapidly communicated, but the second network's QoS priority management reduced that risk significantly. PMID- 17282137 TI - Risk management and biomedical devices. AB - A method of ranking devices for replacement has been successfully trialled at Flinders Medical Centre (FMC). Software developed by Flinders Biomedical Engineering (see www.fbe.org.au) has been distributed to a network of device managers throughout FMC for the entry of easily determined parameters which relate to the likelihood of a device problem occurring and to the consequence of the problem. Algorithms developed by empirical methods calculate total risk scores that correlate well with previously used subjective methods of ranking devices for replacement, safety testing, preventative maintenance or repair. PMID- 17282138 TI - Survey of clinical engineering in developing countries and model for technology acquisition and diffusion. AB - An international survey was conducted in 2003 to assess the status of clinical engineering services delivered to hospitals in developing countries. Data was collected from Asia, Africa, Latin America and Mexico. The responses were compared to two previous studies done in industrialized countries. A model of medical technology acquisition and diffusion is presented. PMID- 17282139 TI - Design of computerized maintenance management system for the chilean naval hospital biomedical engineering department. AB - The purpose of this project was to design and implement a computerized maintenance management system (CMMS) to be used at the Chilean Naval Hospital Biomedical Engineering Department. It is designed to meet the specific needs of this military facility and follows the generic clinical engineering maintenance management system suggested by Association for the Advancement of Medical Instrumentation (AAMI). PMID- 17282140 TI - Conceptual Design and Resources for a General-Purpose Safety and Performance Verification and Validation Toolkit (V2T) for Life-Critical Wireless Medical Device Networks (WMDN). AB - Wireless Medical Device Network (WMDN) deployment is occurring to facilitate ambulatory patient care, increase safer and more intelligent diagnostic and therapeutic capabilities, and improve flexible patient bed configuration that matches census requirements. Patient safety risks exist from delayed or lost WMDN alarm and data streams, however, and non-proprietary Verification and Validation (V2) techniques do not exist. Single-vendor and heterogeneous multi-vendor deployment must be considered, as well as safe and reliable coexistence with other IS technologies sharing similar network components. V2 of even a homogeneous single vendor, single device WMDNS is very complex for several reasons including: absence of industry standards or regulations, unconstrained mobility of patients and devices, and rapid changes in the underlying wireless network modalities. This project will evaluate and recommend appropriate best V2 practices from fields like software and systems engineering to improve a hospitals ability to properly implement and manage the emerging WMDN opportunities and to prevent patient injuries or other serious problems. PMID- 17282141 TI - Issues of device safety in a developing country. AB - Safe use of medical devices is a comprehensive concept with its technical integration. It includes not only its procedural operations but also its vigilance to patient status, correct installation of device, proper user's education and training, appropriate device maintenance, user facility compatibility, and acceptable interference from environment. Consequently, in technology advanced countries, the safety of medical device can be monitored by the operations through both the premarket approval and the postmarket surveillance. This also implies that regulations and standards take its own significant role to the safe operations of medical device. However, with the integrated and hierarchical operation of regulations and standards on medical devices is even non-existent in most of developing and underdeveloping countries. This article presents safety issues of medical devices in these particular circumstances. PMID- 17282142 TI - Medical technology management: from planning to application. AB - Appropriate deployment of technological innovation contributes to improvement in the quality of healthcare delivered, the containment of cost, and access to the healthcare system. Hospitals have been allocating a significant portion of their resources to procuring and managing capital assets; they are continuously faced with demands for new medical equipment and are asked to manage existing inventory for which they are not well prepared. To objectively manage their investment, hospitals are developing medical technology management programs that need pertinent information and planning methodology for integrating new equipment into existing operations as well as for optimizing costs of ownership of all equipment. Clinical engineers can identify technological solutions based on the matching of new medical equipment with hospital's objectives. They can review their institution's overall technological position, determine strengths and weaknesses, develop equipment-selection criteria, supervise installations, train users and monitor post procurement performance to assure meeting of goals. This program, together with cost accounting analysis, will objectively guide the capital assets decision-making process. Cost accounting analysis is a multivariate function that includes determining the amount, based upon a strategic plan and financial resources, of funding to be allocated annually for medical equipment acquisition and replacement. Often this function works closely with clinical engineering to establish equipment useful life and prioritization of acquisition, upgrade, and replacement of inventory within budget confines and without conducting time consuming, individual financial capital project evaluations. PMID- 17282143 TI - Combined photoacoustic and molecular fluorescence imaging in vivo. AB - Because of the overwhelming scattering of light in biological tissues, the spatial resolution and imaging depth of conventional fluorescent imaging is unsatisfactory. Therefore, we present a dual modality imaging technique by combining fluorescence imaging with high-resolution noninvasive photoacoustic tomography (PAT) for the study of an animal tumor model. PAT provides high resolution structural images of tumor angiogenesis, and fluorescence imaging offers high sensitivity to molecular probes for tumor detection. Coregistration of the PAT and fluorescence images was performed on nude mice with M21 human melanoma cell lines with ..v..3 integrin expression. An integrin ..v..3-targeted peptide-ICG conjugated NIR fluorescent contrast agent was used as the molecular probe for tumor detection. PAT was employed to noninvasively image the brain structure and the angiogenesis associated with tumors in mice. The coregistration between the PAT and fluorescence images was used to visualize tumor location, angiogenesis, and brain structure simultaneously. PMID- 17282144 TI - High Resolution 3D Imaging of Lung Tissue using Structured Light Microscopy. AB - A 3D reconstruction microscope has been built in order to investigate the structural details of the airway tree and the vasculature of mouse lungs. The objective is to create an anatomically correct finite element model of a mouse lung in order to validate results from simulations obtained using an existing model of the human lung. The 3D reconstruction microscope consists of a fully automated scanning stage, a vibratome and a structured light optical microscope. Structured light microscopy is a new approach to optical sectioning of tissue and offers several advantages over confocal microscopy. PMID- 17282145 TI - Continuous-wave Near-infrared Topography System and Its Clinical Application. AB - We developed a reflectance continuous-wave near-infrared spectroscopy topography system with multi-source and multi-detector sensor head. A single wavelength (808 nm) laser diode is used as the original light source. With different-measurement approach, we can reconstruct images representing the variety of cerebral blood volume in clinical applications. Phantom experiments have been taken to verify the performance of the system. We also took clinical experiments for brain activities research during acupunctures and have obtained some primarily results. PMID- 17282146 TI - Imaging of epithelial cancer in sub-terahertz electromagnetic wave. AB - We used sub-terahertz (THz) imaging to exam two cross sections of epithelial cancer tissue embedded in paraffin using a 0.19 THz electromagnetic wave. The sub THz imaging system was constructed with a tunnel injection transit time (TUNNETT) diode, a Schottky barrier diode detector and a X-Z stage. We examined the difference between a sub-THz wave absorption in melanoma and nevus tissue. PMID- 17282147 TI - Time resolved optical spectroscopy system for cerebral oxygenation imaging. AB - Optical methods from the near infrared range, in particular the time resolved near infrared spectroscopy offer a new non-invasive, real-time technique for monitoring of the blood perfusion and oxygenation in living tissue. The principle and instrumentation of the time resolved optical spectroscopy system for cereb1ral oxygenation imaging have been described. The system consists of two semiconductor diode lasers and four detection channels which allow for recording of distributions of times of flight of photons at four detection points on the surface of the tissue examined. In the presented configuration it allows recording with 16 source-detector pairs forming a 4x4 grid. Some preliminary results of the laboratory tests and experimental trials curried out with various tissue phantoms are presented. PMID- 17282148 TI - Optical Tomographic and Magnetic Resonance Imaging of Tumor Growth and Regression in Mice treated with VEGF Blockade. AB - Small animal imaging systems now allow researchers to non-invasively monitor the progression of diseases in living small animals and study the efficacy of drugs and treatment protocols. Magnetic resonance imaging (MRI) is an established imaging modality capable of obtaining high resolution anatomical images which are sensitive to blood volume, blood flow, and metabolic rate of oxygen. Optical tomography, on the other hand, is an emerging imaging modality, which, while much lower in spatial resolution and insensitive to blood flow, can separate the effects of oxyhemoglobin, deoxyhemoglobin, and blood volume with high temporal resolution. We illustrate how these imaging modalities can supplement each other and cross validation can be performed by applying both modalities to imaging of tumors growth & regression in mice that are treated with a vascular endothelial growth factor (VEGF) antagonist. PMID- 17282149 TI - Effects of Large Blood Vessel Locations during High Intensity Focused Ultrasound Therapy for Hepatic Tumors: a finite element study. AB - High-Intensity Focused Ultrasound (HIFU) has become a viable alternative for treatment of primary and metastatic liver tumors. We evaluated the effects of presence of a large blood vessel and its distance to the tumor on lesion size during HIFU heating. A finite element method (FEM) was used to obtain the temperature distribution for a transfer equation based on large blood vessels convection effect. In 3-D FEM simulation, a 4-mm diameter, 10-mm height cylindrical tumor tissue was heated by different heating schemes with a large blood vessel (10-mm diameter) located at different positions nearby. The distance between the vessel and the tumor tissue varied from 1 mm to 3 mm. For HIFU therapy, the large blood vessel of different locations do not have significant effect on temperature distribution and thermal dose profile, when the heating duration is short (~2s) or the distance of the large blood vessel from the tumor is larger than 2 mm. The domain of thermal lesion can effectively cover the desired therapeutic region with short ultrasound exposure duration (~2s). PMID- 17282150 TI - Dual-frequency High Intensity Focused Ultrasound (HIFU) Accelerating Therapy. AB - By cutting a spherical focused transducer into two coaxial and confocal transducer elements, a confocal complex transducer used in dual-frequency HIFU system was obtained. The lesion induced by dual-frequency HIFU in freshly excised porcine livers were obviously larger than that induced by conventional single frequency HIFU at the same exposure conditions. The experiment results have also shown that injecting ultrasound contrast agents to the tissue or selecting appropriate difference frequency could further improve the lesioning effect. The dual-frequency HIFU would bring a new approach to accelerate ablating large tumor with HIFU and also provide a new method to miniaturize the conventional HIFU apparatus. PMID- 17282151 TI - Characteristics of Photocytotoxicity with high peak power pulsed irradiation: Comparison of Photodynamic Therapy with two photosensitizers, Photofrin® and mono-L-aspartyl chlorin e6 on prostate cancer cell in vitro. AB - We proposed novel depth-controlled photodynamic therapy (PDT) by varying pulsed laser irradiation condition. We focus on photocytotoxicity suppression under high peak power pulsed irradiation to apply this phenomenon to surface intact therapy to preserve healthy wall of a hollow organ. The relation between laser irradiation condition and cell lethality of rat prostate cancer cell with PDT using practical photosensitizers, mono-L-aspartyl chlorine e6 (ME2906) and Photofrin® was investigated. We found cell lethality suppression from 63 % to 20 % when the irradiated pulsed peak power density ranged from 0.2 to 1.4 mW/cm2with ME2906 mediated PDT. There was no significant photocytotoxicity suppression in case of Photofrin® mediated PDT. Singlet oxygen luminescence from the two different kinds of photosensitizer solution was measured. The pulse peak power dependence of singlet oxygen luminescence intensity correlated with the photocytotoxicity. We think the photocytotoxicity suppression with high peak power pulsed irradiation with ME2906 might be useful for the therapeutic depth controlled PDT without damage on the surface of a hollow organ. PMID- 17282152 TI - Improvement of the resonant cavity applicator for brain tumor hyperthermia - Computer simulation results -. AB - This paper discusses new methods to control the heating pattern of the prototype resonant cavity applicator for deep tumor hyperthermia treatment. We have already confirmed the effectiveness of the developed heating system with experiments using agar phantoms and computer simulations. Here, the following two methods to control the heating pattern were proposed. In the first method, a human body, which was placed in the gap between the two inner electrodes, was only moved towards the electrode. In the second method, in addition to the first method, the diametric ratio of the inner electrodes was changed. According to our computer simulation of heating agar phantoms, we found that the hot spot was moved about 35% of the distance from the center of the agar phantom. It was found that the proposed heating methods were applicable to both deep and regional hyperthermia treatments. PMID- 17282153 TI - A combinatorial method for predicting genetic susceptibility to complex diseases. AB - Recent improvements in the accessibility of high-throughput genotyping have brought a great deal of attention to disease association and susceptibility studies. This paper explores possibility of applying combinatorial methods to disease susceptibility prediction. The proposed combinatorial methods as well as standard statistical methods are applied to publicly available genotype data on Crohn's disease and autoimmune disorders for predicting susceptibility to these diseases. The quality of susceptibility prediction algorithm is assessed using leave-one-out and leave-many-out tests - the disease status of one or several individuals is predicted and compared to the their actual disease status which is initially made unknown to the algorithm. The best prediction rate achieved by the proposed algorithms is 77.78% for Crohn's disease and 64.99% for autoimmune disorders, respectively. PMID- 17282154 TI - Integrative analysis of metabolic disorders by means of medical bioinformatics. AB - We present a strategy of bioinformatics analysis to exploit the current data available both on genomic and metabolic levels and integrate these at novel levels of understanding of metabolic disorders. PathAligner is applied to predict biomedical data based on a given disorder. A case study on urea cycle disorders is demonstrated. Both genetic data and metabolic information are retrieved. We integratively analyze the transcription factors, signaling pathways and associated disorders to interpret the occurrence and regulation of the urea cycle. PMID- 17282155 TI - Study on chromatographic data pre-processing using fuzzy decision making in metabonomics. AB - This paper introduced a straightforward and effective chromatographic data pre processing method developing for utilization prior to chemometric analysis of large metabonomic dataset arising from high performance liquid chromatography. Nucleotides chromatographic fingerprinting in human urines was employed to validate the proposed method. Performance for discrimination cancer samples from healthy urinary sample with principal component analysis was advanced by this method. The first and second principal components could discriminate the two groups by a straight line with precision rate of 75% for cancer samples and 92% for normal samples. Using unprocessed data only 50% cancer samples could be discriminated from healthy cluster. This method was proved to be an effective chromatographic data pre-processing procedure in metabonomics. PMID- 17282156 TI - Sequence-based Protein-Protein Interaction Prediction Optimized for Target Selection in Biological Experiments. AB - A set of protein pairs predicted to be interacting with high ratio of true positive is valuable for target selection in experiments like protein structure determination. Our goal in this paper is to investigate the problem of finding such a set of protein pairs in an organism by machine learning methods. Yeast genome was taken for this study and support vector machine was adopted as the classification model. Domain information of each protein was extracted and transformed into features of a protein pair. We specifically analyzed the effect of negative sample selection based on different principles. We also evaluated the feasibility to adjust the intercept parameter of a trained SVM model to improve the ratio of predicted true positive. Our result shows that the approximate 1:3 ratio of positive samples to negative ones in the testing data can be significantly improved to 2:1 of the positive to negative in the predicted data. PMID- 17282157 TI - A fast algorithm aligning multiple microbial genomic sequences. AB - To compare large genomic DNA sequences of related organisms and of different species, researchers need efficient methods to align many long sequences. We developed a new tool Super Multiple Genome Alignment (SMGA for short), specially for rapid multiple global alignment of genomic sequences. SMGA can align a data set consisting of 50M of 9 enterobacterial genomic sequences in 40 minutes. Our method is faster when compared with other existing multiple sequences alignment method. PMID- 17282158 TI - On the alignment space. AB - Sequences with generalized errors which are called mutations in bioinformatics and generalized error-correcting codes are studied in this paper. In the areas of bioinformatics, computer science and information theory, sequences with generalized errors are discussed respectively for different aims. Firstly, we give the definitions of alignment distance and Levenshtein distance by expansion sequences and discuss their properties and relations. Then the modular structure theory is introduced for strictly describe the expansion sequences. We show that the expansion modular structures of sequences form a Boolean algebra. As applications of the modular structure theory, we give a new and more strict proof of triangle inequality for alignment distance. At last, the definition and construction of generalized error-correcting codes are studied, and some optimal codes with small length are listed. PMID- 17282159 TI - Development of a Portable Blood Sugar Apparatus and GOD Enzyme Strip. AB - A pocket blood sugar apparatus tested by enzyme electrode, which was designed using carbon and silver plasma as conducting materials. Both the work and reference electrodes are applied to the parts of enzyme electrode. The glucose oxidase is taken as the medium of blood sugar measuring. And the range of measuring glucose is about 50mg/dL - 500mgl/dL. It has better linear for the results and fit coefficient arrives at 0.985. Its sensitivity of measurement is higher than current glucose biosensor obviously. A single chip microcomputer, AD mu C812, is used for central control processor of the instrument parts. It measures the output of microampere level currency, which is conduced by blood sugar reacting with the glucose oxidase on the enzyme electrode. And at the same time, the microampere level currency is amplified, processed. Then the results are displayed on LCD. The apparatus are better for measuring blood sugar, and the results are consistent with what the large biochemical instruments get. PMID- 17282160 TI - A novel lactate biosensor. AB - A novel disposable lactate biosensor was reported, which can measure the lactate in whole blood and other bio-fluids rapidly, accurately, expediently and directly. The biosensor was based on two kinds of electron mediator, the ferricyanide and the modified carbon nanotubes (CNT). Lactate oxidase (LOD) was coated on the electrodes. The sensor was fabricated by screen-printed techniques, the sample was supplied through capillary action and the volume was controlled by micro cavity. The liner range is 1~15 mmol/l, precision reaches 0.2 mmol/l . Compared with the respondence of sensor without carbon nanotubes, the characteristic of sensor include that is improved obviously. PMID- 17282161 TI - Study of carbon nanotube modified biosensors for monitoring uric acid and total cholesterol in blood. AB - The carbon nanotube modified biosensors for respectively monitoring uric acid (UA) and total cholesterol in blood were studied. The transducers were based on two screen-printed carbon electrodes, a carbon working electrode and a reference electrode. For UA sensors, uricase was immobilized on the surface of electrodes together with potassium ferrocyanide as electron transfer mediator. For cholesterol sensors, the corresponding enzyme system consists of cholesterol esterase, cholesterol oxidase, peroxidase and potassium ferrocyanide. Multi-wall carbon nanotubes (MWNTs) and single-wall carbon nanotubes (SWNTs) were applied to prompt electron transfer. Experimental results showed that the carbon nanotube modified biosensors offers a reliable calibration profile and stable electrochemical properties. The calibration graphs were linear up to 200mg/L UA and 400mg/dL cholesterol. PMID- 17282162 TI - Development of a novel electronic tongue system using sensor array based on polymer films for liquid phase testing. AB - A novel electronic tongue system had been developed recently in our labs, which was based on impedance measurements of a hybrid sensor array of different polymer films either conjugated conducting polymers (CPs) or rendered conductive polymers by the addition of carbon black (CB) or single wall carbon nanotubes (CNT). In this work, preliminary experiments were carried out on a series of measurements of liquids containing different concentrations of acid (HCl), salt (NaCl), glucose, ethanol and a bitter substance (sodium dehydrocholate). The impedance data have been processed using principal component analysis(PCA) algorithm. The preliminary results demonstrate the feasibility of artificial taste sensing using the polymer films sensory array. PMID- 17282163 TI - The assessment system of human visual spectral sensitivity curve by frequency modulated light. AB - Previous studies used fixed wavelength modulated light to demonstrate the relationship between critical flicker frequency threshold (CFFT) and the factors of the subjects. We address a method to assess the whole human visual spectral sensitivity curve (with the visible range of wavelength) to CFFT by frequency modulated light. The color sensitivity curve of three cones of human eyes is discussed as well as the hardware design of the assessment system is provided. The result shows that this system could be successfully used to experiment the relationship between the stimulus wavelength and the CFFT. PMID- 17282164 TI - Silica nanoparticle tags for capacitive affinity sensors. AB - Capacitive affinity sensors have shown great promise for disposable biosensors but have poor sensitivity as a direct sensor if the analyte molecule is small. In this paper, we report an indirect capacitive affinity sensor with silica nanoparticle tags to enhance the sensitivity for sandwich type of immunoassays. In these experiments, the antibody—antigen—antibody complex (as in the standard indirect sandwich immunoassay) is simulated by a human—IgG antihuman-IgG complex. Silica nanoparticles were synthesized by controlled hydrolysis of TEOS in alcohol and anti-human IgG antibodies were immobilized on them. The capacitive immunosensor comprised of a deposited gold electrode on oxidized silicon with human IgG immobilized on it. After the immunocomplexation process, the nanoparticles manifest by a significant decrease of capacitance compared to when only antihuman-IgG is incubated. PMID- 17282165 TI - Trans-illuminated image restoration of Nevoscope. AB - Nevoscope is an optical imaging device to obtain images of skin-lesions through back-scattered diffused light using trans-illumination to determine abnormalities such as skin-cancers. Due to the nature of the process of transillumination, images obtained from Nevoscope suffer from a dark-field effect. We proposed a two step algorithm to restore Nevoscope images under the trans-illumination mode. First, a background attenuation matrix was extracted from an image of normal skin close to the suspicious abnormality. This matrix was then applied to the trans illuminated image to correct background. Second, the background corrected image was decomposed using wavelet transform. By adjusting the wavelet coefficients judiciously, a denoised and feature enhanced image was obtained. PMID- 17282166 TI - An application of perturbation Monte Carlo in optical tomography. AB - Haemodynamic changes related to activation of the human visual cortex were studied using optical imaging. The change in oxyhaemoglobin concentration in the visual cortex was estimated using a perturbation Monte Carlo (pMC) method. Comparison to a topographic map obtained using the modified Beer-Lambert law and interpolation is given. PMID- 17282167 TI - Near infrared imaging of tissue heterogeneity: probe design and sensitivity analysis. AB - A CW type handheld near infrared tissue oximeter called P-Scan tissue imager was developed for real time imaging of tissue oxygen saturation ([StO2]) and hemoglobin concentration ([Hbt]). The probe consists of eight dual-wavelength light sources (690nm and 830nm) and eight photon detectors forming a 2.5cm X 2.5cm matrix. The local tissue oxygen saturation and hemoglobin concentration was calculated based on optical measurement of absorption coefficients for oxy and deoxy hemoglobin. A superimposition algorithm was developed for direct imaging of local tissue [StO2]/[Hbt] without complex inverse reconstruction. The measurement sensitivity of such a P-Scan device with respect to tumor size, tumor depth, tumor lateral location and tumor optical contrast was studied. First order Born approximation was used to simulate the photon migration in a 2D turbid model with an embedded absorber. The simulation results implied that the P-Scan imager is able to detect the tissue heterogeneity up to 1.5 cm deep with reasonably high sensitivity. Simulation also indicated that among multiple factors that may influence the P-Scan sensitivity, tumor size and tumor depth are dominant factors.* PMID- 17282168 TI - Application of thermovision in the assessment of thermal properthies ophthalmic viscoelastic substances. AB - Ophthalmic viscoelastic devices play a crucial role in cataract surgery today by protecting corneal endothelium, structures of anterior chamber and maintaining space inside the eye for safe manipulation during surgical treatment. Many factors likely affect the corneal endothelium during phacoemulsification procedure. These can be divided into 3 groups: 1. direct mechanical trauma including inadvertent touch of the endothelium by ophthalmic instruments, nuclear fragments, intraocular implant, 2. chemical adverse effects of irrigating solution 3. Influence of ultrasound energy affecting endothelium directly or increased, indirectly by temperature, acoustic contaction or via the generation of free radicals. Among various intraoperative complications that lead to endothelial cell loss thermal injury is potentially relevant. The main source of increased temperature is ultrasound energy delivered into the eye and partially converted into thermal energy. Different viscoelastic substances currently used during cataract surgery have various physical properties e.g. rheology, osmotic strength, viscosity, cohesion that provide different levels of endothelium protection from mechanical, irrigating and ultrasound insult and corneal deturgescence due to osmotic and thermal factors. However thermal factor is thought to be potentially devastating on corneal endothelium. However little is known how different viscoelastic regiments can protect cornea against this kind of injury during cataract surgery. PMID- 17282169 TI - Automated detection algorithm for arteriolar narrowing on fundus images. AB - We have developed a computer-aided diagnosis system (CAD) to detect abnormalities in fundus images. In Japan, ophthalmologists usually detect hypertensive changes by identifying arteriolar narrowing and focal arteriolar narrowing. The purpose of this study is to develop an automated method for detecting arteriolar narrowing and focal arteriolar narrowing on fundus images. The blood vessel candidates were detected by the density analysis method. In blood vessel tracking, a local detection function was used to determine the centerline of the blood vessel. A direction comparison function using three vectors was designed to optimally estimate the next possible location of a blood vessel. After the connectivity of vessel segments was adjusted based on the recognized intersections, the true tree-like structure of the blood vessels was established. The blood vessels were recognized as arteries or veins by hue of HSV color space and their diameters. The arteriolar narrowing was detected by the ratio of diameters (artery vs. vein; A/V ratio). Focal arteriolar narrowing was detected by measuring the diameter of an artery. By applying this method to 100 fundus images, the detection sensitivity for arteriolar narrowing was found to be 76% when the specificity was 91%. Furthermore, by applying this method to 70 other different fundus images, the detection sensitivity for the focal arteriolar narrowing was 75% with 2.9 false positives per image. The number of some false positives is planned to be reduced during the next stage of development. Such an automated detection of abnormal vessels could help ophthalmologists in diagnosing ocular diseases. PMID- 17282170 TI - Frames-Based Denoising in 3D Confocal Microscopy Imaging. AB - In this paper, we propose a novel denoising method for 3D confocal microscopy data based on robust edge detection. Our approach relies on the construction of a non-separable frame system in 3D that incorporates the Sobel operator in dual spatial directions. This multidirectional set of digital filters is capable of robustly detecting edge information by ensemble thresholding of the filtered data. We demonstrate the application of our method to both synthetic and real confocal microscopy data by comparing it to denoising methods based on separable 3D wavelets and 3D median filtering, and report very encouraging results. PMID- 17282171 TI - Functional Imaging: Dynamic Contrast-Enhanced CT using a Distributed-Parameter Physiologic Model for Accessing Stroke and Intracranial Tumor. AB - Functional imaging has the potential to be a practical and widely-available method of studying the pathphysiology of disease using modern CT and MRI technologies. With the high temporal resolution achievable by these technologies, a two-compartment distributed-parameter model, which more accurate represents the tracer concentration within the vascular space, was applied on two patients' data with intracranial tumor and stroke. The parametric maps successfully generated were more informative than the current commercial software packages and the commonly used lumped-parameter compartmental models. PMID- 17282172 TI - A real time simulation model of glucose-insulin metabolism for type 1 diabetes patients. AB - In this paper, a simulation model of glucose-insulin metabolism for Type 1 diabetes patients is presented. The proposed system is based on the combination of Compartmental Models (CMs) and artificial Neural Networks (NNs). This model aims at the development of an accurate system, in order to assist Type 1 diabetes patients to handle their blood glucose profile and recognize dangerous metabolic states. Data from a Type 1 diabetes patient, stored in a database, have been used as input to the hybrid system. The data contain information about measured blood glucose levels, insulin intake, and description of food intake, along with the corresponding time. The data are passed to three separate CMs, which produce estimations about (i) the effect of Short Acting (SA) insulin intake on blood insulin concentration, (ii) the effect of Intermediate Acting (IA) insulin intake on blood insulin concentration, and (iii) the effect of carbohydrate intake on blood glucose absorption from the gut. The outputs of the three CMs are passed to a Recurrent NN (RNN) in order to predict subsequent blood glucose levels. The RNN is trained with the Real Time Recurrent Learning (RTRL) algorithm. The resulted blood glucose predictions are promising for the use of the proposed model for blood glucose level estimation for Type 1 diabetes patients. PMID- 17282173 TI - Computational modeling of vascular clamping: a step toward simulating surgery. AB - The objective of this study was to simulate clamping of the aorta. It is computationally demanding and involves contact between clamp and aorta, large deformations, and fluid-structure interactions (FSI). Models of the aortic root and clamp were created and solve in ADINA, a Finite Element Analysis package. The tissue model was created using a non-linear material. Fluid-structure interactions (FSI) were modeled. The deformation profile of the simulated aorta matched well with that of the real tissue. Clamping of a fluid-filled pressurized aorta, an important first step towards simulating of surgical procedures, was successfully modeled. The simulation was validated by clamping experiments. The modeling techniques developed are also applicable to pre-operative planning of cardiovascular surgery. PMID- 17282174 TI - Pulmonary and cardiovascular integrated model controlled with oxygen consumption. AB - We built a pulmonary and cardiovascugratedar inte- model which is driven by O2 consumption. The integrated model consists of a pulmonary model, a cardiovascular model, a gas exchange model, a respiratory control system model and a cardiovascular control model. To verify the integrated model, we calculated ventilations and cardiac outputs in different O2 consumptions and compared the results with literature values. The literature values are experimental data of healthy men during rest and exercise on a bicycle ergometer. Additionally we checked that the calculated O2 and CO2 transfer rate between blood and alveolar region are consistent with given O2 consumption and CO2 production. PMID- 17282175 TI - A multiscale model for the selection process of ovulatory follicles. AB - The biological meaning of follicular development is to free fertilizable oocytes at the time of ovulation. The selection of ovulatory follicles in mammal ovaries is an FSH-dependent selection process. In this paper, we design a multi-scale model of follicular development, where selection arises from the feedback between the ovaries and the pituitary gland and appeals to control theory concepts. Each ovarian follicle is characterized by a 2D density function giving an age and maturity-structured description of its cell population. The control intervenes in the velocity and loss terms of the conservation law ruling the changes in the density. The numerical outputs of the model, integrated with the finite volume method, are consistent with physiological knowledge. PMID- 17282176 TI - Detecting Phase Coupling of Gastric Interdigestive Pressure Activity via Diagonal Slice Spectra. AB - We propose a new analysis method to detect phase coupling behaviour of the human gastric interdigestive pressure wave that has been acquired by a telemetric capsule-like mini-robot. The method is referred to as diagonal slice spectra, which are the Fourier transforms of the diagonal slices of the triple correlation and can detect the phase coupling and coupled components respectively. It is shown that nonlinear quadratic phase coupling occurs during gastric contraction (phase II), whereas no distinct phase coupling occurs during gastric motor quiescence (phase I). PMID- 17282177 TI - Increased Phase Synchronization between Intracranial Pressure and Arterial Blood Pressure during Elevated Intracranial Pressure in Dogs. AB - We applied the concept of "phase synchronization" from nonlinear dynamics to the complex relationship between intracranial pressure (ICP) and arterial blood pressure (ABP) signals. This method is based on multiresolution wavelet transform (MRWT) in which the signals are divided into different frequency bands. We examined ICP and ABP signals from anaesthetized dogs, exploring normal ICP and elevated ICP by 1~3 ml injection of saline into the cerebral ventricles. Phase synchronization analyses show an interesting phenomenon of phase reset from relatively uniform phase distribution to phase clustering around 0° after injection. To further quantitatively measure phase synchronization, phase coherence is used to distinguish the dynamics of normal ICP and elevated ICP by saline injection. Elevated ICP exhibits higher phase coherence than that of normal ICP. The results suggest that the association between ICP and ABP may involve nonlinear mechanisms of regulation. The clinical application of this method is in investigation. PMID- 17282178 TI - Sensitivity of detrended fluctuation analysis applied to heart rate variability of preterm newborns. AB - Detrended fluctuation analysis (DFA), a fractal analysis method which is widely used in heart rate variability (HRV) studies, is used to analyze the scaling behaviour of RR interval series of preterm neonates. The average scaling behaviour, calculated using 30000 RR intervals (3 - 4 hours), is characterized by a scaling exponent of 1.4 ± 0.1 at small scales (n ≤ 20) and a smaller exponent of 1.0 ± 0.1 at larger scales. It is shown that the scaling behaviour is not constant over such long segments and how heart rate patterns, associated with specific physiological mechanisms, contribute to the observed variation of the scaling exponents. The effect of the two most important patterns, spikes (either due to faulty peak detection or true decelerations in heart rate) and periodic fluctuations, on the scaling behaviour is investigated. PMID- 17282179 TI - Intelligent analysis of biosignals. AB - While biosignal analysis has been a mainstay in many medical applications for a number of decades, notably in cardiology, problems remain in the analysis of high volume data and in comparison among time series. Effective comparisons can determine if the state of a particular patient has changed significantly. These comparisons are useful in both long-term and short-term monitoring. Methods will vary depending on the type of signal and the situation. Intelligent agents permit the activation of the appropriate analysis for the signal and the current situation. Agents are defined in terms of both methodology and function. The agent system is described and illustrated in applications to cardiology and neurology. PMID- 17282180 TI - Classification of Impulse Oscillometric Patterns of Lung Function in Asthmatic Children using Artificial Neural Networks. AB - Impulse Oscillometry (IOS) is an innovative patient-friendly pulmonary testing technique which measures the respiratory system impedance (Z) by using the spectral components of pressure to flow ratio which yields resistance and reactance values at different frequencies. The high dimensionality of IOS measurement data makes the analysis of this information difficult. Artificial Neural Networks (ANNs) are mathematical models composed of a large number of highly interconnected neurons that are able to learn and generalize from data. An ANN-based approach to the analysis of IOS data can potentially provide an efficient and automatic method to recognize and classify pulmonary diseases. This would help characterize major respiratory illnesses such as asthma based on IOS measurements. Asthma can be difficult to diagnose, because the symptoms are sometimes similar to other lung conditions. A data set composed of 361 impulse oscillometric patterns from asthmatic children was used in this study. The ANN was capable of distinguishing between relatively constricted and nonconstricted airway conditions in these patients. Using all of the 361 patterns during training as well as in the feed-forward stage, a classification accuracy of 95.01% was obtained for validation. When the ANN was presented with only 60% of the original 361 patterns in the data set during training and with the remaining 40% as unseen patterns, the generalization stage, a classification accuracy of 98.61% was achieved. PMID- 17282181 TI - Combined Bispectral and Bicoherency approach for Catastrophic Arrhythmia Classification. AB - Quantitative classification of cardiac arrhythmia is an important tool in ICU and CCU that enables on line monitoring of the cardiac activities. Among fatal arrhythmias are atrial fibraliation (AF), ventricular tachycardia (VT), and ventricular fibrillation that require special algorithms for detection and so for direct medical actions. In this paper, a combined bispectrum and bicoherency classification algorithm is introduced. It is based on extracting diagnostic features from the bispectrum contours and the bicoherency indices that better describe the arrhythmia. A simple classification scheme utilizing these features showed notable sensitivity and specificity. The obtained results are found comparable to the state of the art algorithms with the ability of being integrated for on line monitoring and classification. PMID- 17282183 TI - Modeling cardiac activation and the impact of a discontinuous myocardium. AB - Methods have been developed for modeling cardiac activation which accounts for detailed myocardial geometric structures derived from specific tissue samples. This modeling allows both study and analysis of the effects of cleavage planes and other structural barriers to myocardial current flow. Specialized numerical and computational procedures have been developed to enable this modeling. The results that have been obtained clearly show the impact that discontinuities have in the formation of transmural virtual sources and also assist in better understanding experimental recordings. We are continuing to increase our capacity for modeling larger tissue samples, particularly those capable of sustaining reentry. PMID- 17282182 TI - Simulation study of transmural cellular electrical properties in failed human heart. AB - This paper presents simulation study of the action potential waveforms of different ventricular cell types based on experimental studies of transmural electrophysiological heterogeneities in control and failing human hearts. The results show that prolonged action potential duration (APD) and APD rate adaptation are markedly transmural heterogeneous in heart failure than those in controlled heart which may be due to enhanced transmural heterogeneities of ICaL and I ks in myocytes. This mathematical model of the failed heart cellular action potential may also serve as a paradigm for studying the failed heart's mechanical properties with excitation-contraction coupling. PMID- 17282184 TI - An electrical heart model incorporating real geometry and motion. AB - This paper describes an electrical model of the ventricles incorporating real geometry and motion. Cardiac geometry and motion is obtained from segmentations of multiple-slice MRI time sequences. A static heart model developed previously is deformed to match the observed geometry using a novel shape registration algorithm. The resulting electrocardiograms and body surface potential maps are compared to a static simulation in the resting heart. These results demonstrate that introducing motion into the cardiac model modifies the ECG during the T wave at peak contraction of the ventricles. PMID- 17282185 TI - A meshfree method for solving cardiac electrical propagation. AB - We present a novel numerical scheme to accurately and efficiently simulate the spatiotemporal electrical propagation for three dimensional heart model. A meshfree particle representation of myocardial volume is first developed, upon which the electrical propagation can be obtained using the element-free Galerkin (EFG) method for the FitzHugh-Nagumo model. This method is based on a sufficient amount of sampling nodes of the three-dimensional myocardial volume, but without the needs to construct the often expensive and complicated mesh structure between these nodes. Compared to the traditional finite element method, this new approach provides a more efficient numerical method to model the effects of the myocardial geometrical complexity and material inhomogeneity/anisotropicness. Experiments on synthetic and real heart geometries with uniform and nonuniform diffuse materials are presented. Related implementation issues are also discussed. PMID- 17282186 TI - Upgrading undergraduate biomedical engineering laboratory training. AB - This paper presents the upgrading of biomedical engineering laboratory training at the Department of Medical Instrumentation Technology of the Technological Educational Institution of Athens (TEI-A), taking place in the framework of the "Upgrading of Undergraduate Curricula of TEI-A" project. The educational material of selected specialized laboratory sectors is totally renewed, and new sectors are introduced, so that student-centered learning is promoted utilizing advanced computer-enhanced educational environments. The current implementation status is presented for the laboratories dealing with biosignal acquisition, medical data digital processing and, more extensively, computer networks applications in medicine, where a training application simulating a Radiology Department computer network was developed. Benefits of the use of a balanced training approach, combining hands-on experience with computer simulations, are discussed. PMID- 17282187 TI - A Premier Comprehensive Curriculum in Biomedical Engineering within the Middle East and Northern African Region. AB - While Biomedical Engineering Education is thus far undergoing advancement in leading institutions worldwide [1-3], there are many areas of the globe where it is still absent. This article depicts the experience behind the development of a premier comprehensive undergraduate program in Biomedical Engineering in Lebanon and conceivably the Arab world. The program has been carefully planned with deliberation toward prospective accreditation by the Accreditation Board for Engineering and Technology, Inc. (ABET, Baltimore, MD) [4]. The first three years, with this four-year curriculum, have revealed encouraging outcomes. Nevertheless, the challenges were quite intricate. PMID- 17282188 TI - The first experience of a dedicated biomedical education unit at the university of franche-comte. AB - Biomedical activity is rapidly expanding. Actually, the demand for hi-tech technologies in health is in constant increase. At the Franche-Comte High Institute of Engineers (ISIFC) an engineer can acquire the knowledge and skills to carry out various tasks in biomedical engineering field including academic research, in-hospital devices maintenance or industrial development. The main advantage of the ISIFC is that it offers an exceptional multidisciplinary programme thank to close cooperation between Besancon University Hospital professionals and Engineering Sciences professors and researchers. As a result, the graduates obtain real experience in the both fields. The majority of the ISIFC engineers are employed by firms producing and/or commercializing health oriented materials and equipments such as Alcis, Arthesis, Aventis Pasteur, Biomerieux, Imasonic, Medos, Statice Sante, Sophysa, Symbios, Praxim, Protheos, Tornier, Zimmer etc. PMID- 17282189 TI - Upgrading BME studies in Buenos Aires, Argentine. Favaloro University. AB - The Favaloro University initiated the academic path in biomedical sciences in Buenos Aires, Argentina. As a very promising area, the biomedical world offers the integration between several domains, complementing medicine with engineering topics. The profile of the graduated students proved to be very versatile, allowing their instantaneous incorporation to the competitive market in this vast field. The university strategy is to concentrate basic science in the first 3 years and add the specific biological/medical concepts in the last 2 years. The students achieve a bachelor degree that integrates their knowledge in basic sciences. Afterwards, they attend a professional 2 year cycle, choosing between biomedical, physics and medical computing branches. The results proved to be effective in terms of professional and academic quality, market insertion and even the creation of promising seeds for future enterprises. PMID- 17282190 TI - Clinical application driven physiology in biomedical engineering laboratory course education. AB - An innovative biomedical engineering (BME) laboratory course was developed to integrate wireless biotechnology with a hands on learning approach. In recent years the need for biomedical engineers in research and industry has increased dramatically. This requires novel strategies for training BME students in both engineering principles and clinical applications. BME students should be prepared with an appropriate skill set for real-world problems. BME education requires hands on learning with cutting edge technology to produce students ready to solve clinical problems in both research and industry. Including a wide range of BME clinical and rehabilitation applications increases student interest. A wide range of BME laboratories was designed to encompass both the basics of physiological signals and how to effectively utilize them in clinical applications. These clinical application interfaces are critical for students to understand how physiological signals may be manipulated to extract meaningful benefits for various medical disorders and rehabilitation needs. The biomedical engineering laboratory course presented in this paper was implemented and evaluated at several universities. Utilizing a virtual environment for practical applications bridges the gap between fundamentals and real world designs. PMID- 17282191 TI - Ambulance 3G. AB - Minimising the time required for a patient to receive primary care has always been the concern of the Accidents and Emergency units. Ambulances are usually the first to arrive on the scene and to administer first aid. However, as the time that it takes to transfer the patient to the hospital increases, so does the fatality rate. In this paper, a mobile teleconsultation system is presented, based primarily on third generation mobile links and on Wi-Fi hotspots around a city. This system can be installed inside an ambulance and will permit high resolution videoconferencing between the moving vehicle and a doctor or a consultant within a base station (usually a hospital). In addition to video and voice, high quality still images and screenshots from medical equipment can also be sent. The test was carried out in Athens, Greece where a 3G system was recently deployed by Vodafone. The results show that the system can perform satisfactory in most conditions and can effectively increase the patient's quality of service, while having a modest cost. PMID- 17282192 TI - A PDA-Based ECG Beat Detector for Home Cardiac Care. AB - Recent rapid growth in mobile computing technologies enables telemedicine applications to operate on mobile devices. Our focus is on the design of an integrated electrocardiogram (ECG) beat detector on a Personal Digital Assistant (PDA) platform for the health screening process. The ECG beat detector module will be supported by the PDA version of Personal Health Information Management System (PHIMS) and Facilitated Accurate Referral Management System (FARMS) through wireless network infrastructure as a home-based mobile cardiac monitoring solution. PMID- 17282193 TI - Medical device databases: a scoping study. AB - Databases of medical devices were identified via complex search strategies to discover breadth and depth of coverage. The databases could be categorised into three types: Product, Business and Regulation. Evaluation of the databases uncovered several issues including: lack of continuity relating to the level of information provided; and little or no evidence that evaluation criteria has been applied to the databases. Other results of the scoping study suggest that a comprehensive medical device database must address the information requirements of a diverse group of stakeholders including multiple professional disciplines as well as patients and their carers. In order to support the needs of this disparate group of users, it is essential to develop a policy to support clear pathways to validate information gathering, representation, and retrieval activities. PMID- 17282194 TI - Information Flow and Data Reduction in the ECG Interpretation Process. AB - In result of ECG interpretation process the diagnostic outcome summarizes all the principal information included in the raw recording. This process is investigated in this paper in data flow and data reduction aspects being of particular impotrance for implementation of distributed ECG interpretation in a wireless network. The detailed analysis of existing software and cardiologists societies guidelines reduces the whole interpretation process to the network of modules interconnected by data busses. Each module is then described by the computational reliability and by expected data streams at its inputs and outputs, from which the average data reduction ratio is computed. These parameters are consequently used for a design of interpretation architecture improving the diagnostic reliability and oriented to appropriate task sharing between the remote wearable recorder and the interpretive center. PMID- 17282196 TI - Scalable ECG Compression for Long-Term Home Health Care. AB - Most current Holter devices monitor the ECG for 24 to 72 hours. However, for the accurate diagnosis of many cardiac diseases, especially for the wide variety of asymptomatic cases, continuous ECG monitoring for weeks or even months may be required. In this paper, we focus on the issue of ECG compression during long term monitoring of the patient. The patient may be at home, at work, or even on a trip. A scalable compression scheme is proposed which ensures optimal signal quality given the limited physical storage on the wearable device. When necessary, the signal quality is progressively and gently degraded in order to adapt to environmental and the patient's conditions. Details of the proposed scheme are described and sample results are presented. PMID- 17282195 TI - Indoor Telemedicine in Hospital: a PDA-based Flexible Solution for Wireless Monitoring and Database Integration. AB - An integrated information flexible system is proposed in this paper for indoor medical applications. The system is intended to provide clinicians with a portable device enabling to discover and recognize patients and easily access their electronic record in a fast and secure way for consultation or updating. Moreover the developed solution allows communication with medical equipments for wireless monitoring of patients biosignals. Requirements for such a system are therefore high flexibility and mobility, as well as fast and secure wireless communication. These features were achieved combining the use of Bluetooth technology with a Personal Digital Assistant, which was provided with a multilayer software architecture to allow easy access to Hospital database and to communicate with external medical devices. A prototype was also realized and the testing phase has indicated good performances on both patient discovery and wireless monitoring. PMID- 17282197 TI - Hemodynamic performance in-vivo of a new ventricular assist device. AB - Nowadays, circulatory support has become a common practice in medicine and a standard in the treatments of Cardio Vascular Disease (CVD). A new Pneumatic Ventricular Assist Device (VAD) has been developed in Mexico City. This paper shows the first results of acute in-vivo trials, intended to verify the new system for providing physiological flows and pressures. Two VADs were implanted to as right (RVAD), left (LVAD) support in a 65 kg pig. The support time was 20 minutes with RVAD, 20 minutes with LVAD and 20 minutes with Biventricular (BiVAD). The VAD proved its capability to maintain physiological parameters during the support time. We are satisfied with the results of this trial, and we believe this study will ascertain the first step on the next phase of invivo trials. PMID- 17282198 TI - Development of an Implantable and Ambulatory"Plug and Play" Transventricle LVAD. PMID- 17282199 TI - Detection and avoiding ventricular suction of ventricular assist devices. AB - Continuous flow blood pumps, such as axial flow and centrifugal pumps, have been gaining interest as circulatory devices for total artificial hearts (TAHs) and a biventricular assist device (BVAD) because of their smaller size and simpler structure compared to pulsatile pumps. However, continuous flow pumps are more prone to suction of the left ventricle than pulsatile pumps are. Sudden increases in flow rate to meet changes in physiological demand, especially in the left pump, often cause ventricle suction. In this study, a control algorithm to prevent suction from occurring in the left ventricle by controlling the rotational speed of the right pump, instead of reducing the cardiac output of the left pump, was developed and investigated. The method was tested in acute animal experiments with calves. The results indicate that this proposed method is capable of preventing suction and could simultaneously maintain circulatory control. A key advantage of this control system is that flow rates can be maximized while avoiding ventricle suction conditions particularly when the circulatory system is unstable such as in a the first few days after operation. PMID- 17282200 TI - Development of an Artificial Myocardium using a Covalent Shape-memory Alloy Fiber and its Cardiovascular Diagnostic Response. AB - The authors have been developing a newly-designed totally-implantable artificial myocardium using a covalent shape-memory alloy fibre (Biometal®, Toki Corporation), which is attached onto the ventricular wall and is also capable of supporting the natural ventricular contraction. This mechanical system consists of a contraction assistive device, which is made of Ti-Ni alloy. And the phenomenon of the martensitic transformation of the alloy was employed to achieve the physiologic motion of the device. The diameter of the alloy wire could be selected from 45 to 250μm. In this study, the basic characteristics of the fiber of 150μm was examined to design the sophisticated mechano-electric myocardium. The stress generated by the fiber was 400gf under the pulsatile driving condition (0.4W, 1Hz). Therefore it was indicated that the effective assistance might be achieved by using the Biometal shape-memory alloy fiber. PMID- 17282201 TI - Simulation of the human cardiovascular system for real-time physical interaction with an assist device. AB - In the development of left ventricular assist devices (LVADs), numerical simulations of the cardiovascular (CV) system have been widely used. Further, electro-hydraulic simulations have been developed to evaluate the performance of a physical LVAD prototype against a numerical model of the CV system. The effects of dynamic cardiac compression (DCC) have been less well modeled. This paper considers the interaction between a DCC device and a closed-loop numerical model of the cardiovascular system, which is specifically developed. The model is operated in realtime, and interfaced to the physical assist device for realistic testing. Assist control strategies are compared: constant pressure DCC, and volume-proportional pressure to simulate cardiomyoplasty. The model shows that applying equal pressure to both ventricles causes inflation of the left ventricle. PMID- 17282203 TI - Information Rate of Neural Spike Trains in Response to Sinusoidal Electric Stimuli in the Presence of a Pseudo-spontaneous Activity. AB - This article presents an analysis of the information rate of neural spike trains in an auditory nerve fiber (ANF) model stimulated extracellularly by sinusoidal electric stimuli under the case where a high-rate pulsatile waveform is presented as a conditioner for increasing the across-fiber-independency, i.e., desynchronization. In the computer simulation, stimulus current waveforms were presented repeatedly to a stimulating electrode located 1 mm above the 26th node of Ranvier, in an ANF axon model having 50 nodes of Ranvier, each consisting of stochastic sodium and potassium channels. From spike firing times recorded at the 36th node of Ranvier, the inter spike intervals were generated and then "total" and "noise" entropies were estimated to obtain the mutual information and information rate of the spike trains. In the present article, it is shown that at a specific amplitude of sinusoidal waveforms, the possibility to encode the sinusoidal function with various amplitudes became greater (enlarging dynamic range), as well as the information rate was found to be maximized. It was implied that setting the amplitude of sinusoids to the specific values which maximize the information rate might contribute to efficiently encoding information under the high-rate pulsatile stimulation in cochlear prostheses. PMID- 17282202 TI - Artificial gas exchange. PMID- 17282204 TI - Quantifying the contribution of cross-correlation in stimulus feature discrimination in an ensemble of retinal ganglion cells. AB - Based on Poisson variability, the strength of cross-correlation of two spike trains was quantified by a cross-correlation index (CCI). Discriminant analysis with CCI was used to quantify the contribution of cross-correlation in stimulus feature discrimination in an ensemble of retinal ganglion cells. Compared with simulated Poisson cell pair, it was found that cross-correlation carried useful information for stimulus feature discrimination and with the cross-correlation included in the analysis, the color and the intensity discrimination ability of a cell pair increase 4.2% and 2.7%, respectively. PMID- 17282205 TI - Signal detection of salient visual features by the early visual pathway. AB - The role of the lateral geniculate nucleus (LGN) of the thalamus in visual encoding remains an open question. Visual stimulation of the LGN produces two distinct types of responses: tonic and burst. It has been suggested that these two modes of response could serve to transmit high fidelity features of the visual world (tonic) or robustly detect salient features of the visual world (burst). Here, we use a combination of experimental and simulated LGN responses to natural scene movies to investigate the specificity of burst generation, and their role in signaling salient features of the visual scene. LGN responses to excitatory stimulus features were simulated with and without bursts and analyzed using signal detection theory. We find that bursts enhance detection of the onset of excitatory features as compared to purely tonic firing, and that algorithms inspired by this type of framework can enhance the transmission of visual information in situations with limited bandwidth. PMID- 17282206 TI - Spikes, Local Field Potentials, and Electrocorticogram Characterization during Motor Learning in Rats for Brain Machine Interface Tasks. AB - Brain machine interface development typically falls into two arenas, invasive extracellular recording and non-invasive electroencephalogram recording methods. The relationship between action potentials and field potentials is not well understood, and investigation of interrelationships may improve design of neuroprosthetic control systems. Rats were trained on a motor learning task whereby they had to insert their noses into an aperture while simultaneously pressing down on levers with their forepaws; spikes, local field potentials (LFPs), and electrocorticograms (ECoGs) over the motor cortex were recorded and characterized. Preliminary results suggest that the LFP activity in lower cortical layers oscillates with the ECoG. PMID- 17282207 TI - Neural Codes in Human Extracranial EEG: Identification of Epilepsy Features. AB - Features of epilepsy from human extracranial EEG recordings were obtained using the wavelet artificial neural network (WANN). The WANN is also a robust signal processing tool for the estimation of nonlinear time-frequency relation and it had previously been shown to be able to classify and predict state transitions in the in-vitro hippocampal slice model exhibiting spontaneous epilepsy. The variations in the power-frequency spectrum were analyzed. The accuracy of state classification was improved when more training data was used. The corresponding changes in synaptic weights between artificial neural units associated with more training data was studied to determine the correlations between learning in WANN and frequency information in human epilepsy. PMID- 17282208 TI - A computer assisted method for guide-wore and catheter evaluation. AB - We developed a method for testing guide wires and catheters that realistically evaluates the forces applied to anatomical structures by these instruments during urological procedures. The placement of guide wires and catheters to gain access to the upper urinary tract can induce undesirable stress on the tissue. Previous studies have characterized wire/catheter performances base on their physical properties, such as stiffness and friction coefficient. However, the results of these studies do not directly quantify their effect on the tissues. Additionally, individual physical properties do not entirely characterize the behavior of the wire/catheter ensemble. Our model utilizes a computer-controlled test stand that simulates the urological environment by including a tortuous path and a stone obstruction. Experimental results indicate that the method shows significant promise in reflecting wire/catheter performance data in congruence with reliable real-life measures of stress upon relevant anatomical structures. Furthermore, due to the modularity of the approach, the model can be easily reconfigured to simulate environments from other medical fields. PMID- 17282209 TI - Automated leakage current measurement for medical equipment safety. AB - Electrical safety is always an important item of medical equipment in hospital. With the development of clinical engineering, the electric safety testing has become a routine procedure for the unit of clinical engineering in hospital. Among the parameters of safety standard of medical equipment, the leakage currents are more important than others. This study is aimed in the measurement of different leakage currents. An intelligent and digital tester was applied to test the safety quality of medical instrument automatically. This tester was based on a chip-computer (INTER 8031). This tester was designed to be able to set up as normal status or single failure status for automatic test by electric relays. All the results, free from manual errors, are displayed by means of a LCD unit and printed by a micro-printer. The output of high accuracy is also an advantage of this instrument, which is based on a precise signal detection electrical circuit and adaptive filter. This tester can be easily used for the clinic unit follow the standard of China GB9706 as well as IEC standard 601 and UL2601. PMID- 17282210 TI - Effects of thrombolysis with ultrasound on the structure of erythrocyte and its safety threshold. AB - The study was to investigate thrombolysis in vivo with ultrasound, and to discuss effects of thrombolysis with ultrasound on the structure of erythrocyte and its safety threshold, under different ultrasound intensity and exposure time. The structure of erythrocyte in thrombus was evaluated under light microscope. The relationship between the structure of erythrocyte in thrombus and ultrasound intensity and exposure time was obtained. The results showed that ultrasound eliminated the thrombus. According to the change of the structure of erythrocyte in thrombus and ultrasound intensity and exposure time, the effects of thrombolysis with ultrasound could be divided into three kinds of areas: the A, B, C area. The area A was the safe area, the area B was the relatively safe area, and the area C was the irreversible damage area. The study suggested that ultrasound intensity and exposure time had significant impact on the structure of erythrocyte. Too much ultrasound intensity or too long exposure time could cause erythrocytes irreversible damaged. It could accelerate thrombolysis and shorten the exposure time that the ultrasound intensity was little bit increased. This study of effects of thrombolysis with ultrasound on the structure of erythrocyte and its safety threshold were important for practical applications. PMID- 17282211 TI - Effects of Time-Varying Magnetic Fields on Transient increase in Intracellular Ca2+Concentration of Cultured Cells. AB - We tested the effects of some kinds of time-varying magnetic fields (0-1.2T) on neurotransmitter-induced transient increases in intracellular Ca2+concentration ([Ca2+]) of cultured chromaffin and HeLa cells. After these cells were exposed for 2 hours to these magnetic fields, transient increases in [Ca2+]i by addition of acetylcholine or histamine were measured. In control cells, after addition of these neurotransmitters [Ca2+]i was increased immediately and then decreased with time in both cells. But, addition of these drugs to the magnetic fields exposed cells increased [Ca2+]i to a level similar to that for control cells. These results suggest that the transient increases in [Ca2+]i were not significantly influenced by the magnetic fields used in this experiment. PMID- 17282212 TI - Development and transformation of working mode in clinical engineering department. AB - This paper starts with analyzing the development and history of clinical engineering in China, analyzing the macro-environment of clinical engineering and summarizing the practice experiences of Chinese and foreign CE department. It puts forward a new idea that clinical engineering working mode should be changed from "working around repairing" to "working around equipment quality control and safety management". PMID- 17282213 TI - Image registration in myocardial perfusion MRI. AB - In clinical first-pass myocardial perfusion studies, physiological and patient motions are inevitable. Such motions impair the sensitivity and reliability in assessing myocardial perfusion abnormalities. The current study aims to correct the misregistration of myocardium during first-pass perfusion imaging by using a normalized mutual information approach. Multi-slice registrations were performed in 15 sets of clinical data sets. The proposed registration procedure was found to be fairly robust. With such registration, ROI time courses from normal myocardium and infarcted myocardium were improved, offering potential to quantify myocardial perfusion parameters in a more reliable manner. PMID- 17282214 TI - Comparison of Point Similarity Measures for Atlas-based Registration of MRI Brain Images. AB - High-dimensional deformable registration of MRI brain images is presented here. The deformation is driven by local forces estimated from point similarities based on joint histogram and with the use of prior information obtained from tissue probability maps available in selected commonly used brain atlases. Three point similarity measures are tested in an experiment with data obtained from standard Simulated Brain Database. PMID- 17282215 TI - A Segmentation Scheme of Brainstem and Cerebellum using Scale-Based Fuzzy Connectedness and Deformable Contour Model. AB - A semi-automatic multiple-stage segmentation scheme of brainstem and cerebellum is proposed in this paper. This proposed scheme contains a modified Scale-based Fuzzy Connectedness (FC) algorithm, a morphology operator, Chain code, and Active Contour Mode (ACM). A modified Scale-based FC is utilized to delivery a rough segmentation, a morphology operator and Chain code are used to compensate the uncompleted small regions and derive an initial contour, and ACM is employed to obtain the final object boundary with the aid of the initial contour from the previous stages. The experimental results verify that the segmentation results using the proposed scheme are more accurate than using a single algorithm based on a Scale-Based FC method. PMID- 17282216 TI - Adaboost and Support Vector Machines for White Matter Lesion Segmentation in MR Images. AB - The use of two powerful classification techniques (boosting and SVM) is explored for the segmentation of white-matter lesions in the MRI scans of human brain. Simple features are generated from Proton Density (PD) scans. Radial Basis Function (RBF) based Adaboost technique and Support Vector Machines (SVM) are employed for this task. The classifiers are trained on severe, moderate and mild cases. The segmentation is performed in T1 acquisition space rather than standard space (with more slices). Hence, the proposed approach requires less time for manual verification. The results indicate that the proposed approach can handle MR field inhomogeneities quite well and is completely independent from manual selection process so that it can be run under batch mode. Segmentation performance comparison with manual detection is also provided. PMID- 17282218 TI - Intensity robust viscous fluid deformation based morphometry using regionally adapted mutual information. AB - This paper describes an approach to fine scale non-rigid registration for mapping patterns of tissue volume loss in serial MRI studies of the brain. Specifically it addresses the important confound of diffuse tissue contrast changes which can influence local sub-voxel estimates of volume change. Such changes can be induced by neurodegenerative or neurodevelopmental processes, which not only modify apparent tissue volume, but also modify tissue integrity and its resulting MRI contrast parameters. We derive an approach to the voxel-wise maximization of regional mutual information (RMI) and use this to drive a viscous fluid deformation model between images. This provides a topology preserving map of local changes in volume between time points that is robust to regional changes in tissue contrast. Comparisons with current methodology are included showing that the approach provides a significant reduction in errors when tissue contrast varies locally between MRI acquisitions. PMID- 17282217 TI - Image Segmentation, Registration and Visualization of Serial MR Images for Therapeutic Assessment of Polycystic Kidney Disease in Transgenic Mice. AB - In vivo small animal imaging provides a powerful tool for the study of a variety of diseases. Magnetic resonance imaging (MRI) has become an established technology for the assessment of therapies. In this study, we used high resolution MRI to evaluate polycystic kidney disease (PKD) in transgenic mice. We used a customized mouse coil to acquire serial MR images from both wide-type and transgenic PKD mice immediately prior to, and 2-week and 4-week after therapy. We developed image segmentation, registration and visualization methods for this novel imaging application. We measured the kidney volumes for each mouse to assess the efficacy of the therapy. The segmentation results show that the kidney volumes are consistent, which are 348.7 ± 19.7 mm3for wild-type mice and 756.3 ± 44.1 mm3for transgenic mice, respectively. The image analysis methods provide a useful tool for this new application. PMID- 17282219 TI - A new thermal system for tumor treatment. AB - A new thermal system for tumor treatment was designed to enhance the curative effects while minimizing invasion to the surrounding healthy tissue. This system includes LN2cryosurgery and RF ablation, which can be used separately or simultaneously. A heat transfer model describing the thermal field during treatments was established. The SAR distribution was assumed to be resulted from an infinite linear source. Numerical simulation of the temperature distributions inside the tissue was performed using Fluent 6.1. Parameters such as the RF power, nitrogen flow rate, and the starting time of each treatment were adjusted to control the treatment region. The simulation results demonstrated that the RF power is the key factor to control the heating and thawing process, while the protecting nitrogen flow can adjust the heating rate slightly. PMID- 17282220 TI - Numerical Calculations of Heating Patterns around a Coaxial-Slot Antenna for Microwave Hyperthermia - Aiming at Treatment of Brain Tumor and Bile Duct Carcinoma-. AB - Hyperthermia is one of the modalities for cancer treatment, utilizing the difference of thermal sensitivity between tumor and normal tissue. The authors have developed a coaxial-slot antenna for microwave hyperthermia. In this paper, calculated results of temperature distributions around the coaxial-slot antenna for the treatment of brain tumor and bile duct carcinoma are described. PMID- 17282221 TI - Effective cryopreservation of human embryonic stem cells by programmed freezing. AB - Cryopreservation of human embryonic stem cells is an important and unsolved problem. A computer-controlled programmable cooler is used in the preservation of ES cells. Several effects have been experimentally studied, which include the cooling rate, the seeding temperature, the terminative temperature before the sample is plunged into liquid nitrogen. It is found that the constitution of cryoprotective agents is Me2SO+FBS+DMEM(1:3:6,v/v/v), and the sample is cooled from 0 °C to -35 °C with a cooling rate of 0.5 °C/min (seeding at 10 °C), and then being plunged into the liquid nitrogen immediately. The high survival rate (81.8%) is obtained. The cryopreserved human ES cells have been cultivated for prolonged periods and retained the properties of pluripotent cells, they have a normal karyotype and show the histochemical staining for alkaline phosphatase. PMID- 17282222 TI - Performance evaluation of a novel liquid nitrogen cryoprobe. AB - A novel liquid nitrogen cryoprobe is developed in the present study. The inlet, handle, the vapor-liquid separator and the heat transfer segment of the cryoprobe are designed to be detachable. This flexible construction provides many distinct features, such as good maneuverability, high safety and low cost. A new vapor liquid separator is made to ensure the free flow of the liquid nitrogen and increase the probe freezing capacity. The wall temperatures at the different locations along the cryoprobe are measured in the air, gel and brine, with the various driven pressure ranging from 0.3 to 0.6 MPa. The results are compared to the other probe. It is found that the precooling time of the probe is shortened significantly. The present cryoprobe offers better cooling performance to the existing cryoprobe. The heat flux transferred from the surrounding air or brine to the cryoprobe is estimated, and it is concluded that the boiling pattern in the probe is the film boiling and suggestions for further improvement of the cryoprobe's performance is made based on the analysis. PMID- 17282223 TI - Effect of configuration between cryoprobe and large blood vessels on the tissue freezing during cryosurgery. AB - For accurate predictions of the tissue temperature distribution during cryosurgery a thermal model should incorporate the individual impact of large blood vessels. In presence of large vessel, configuring cryoprobe becomes very important because misplacement of cryoprobes may result in either inadequate cooling temperatures in the target tissue due to the heating nature of large vessels or undesired damage to the downstream healthy tissues and organs as a result of arresting of key vessels. In this article, typical vascular models are applied to investigate the effects of large blood vessels and cryoprobe configurations on the transient temperature profiles of cooled tissues during cryosurgery. The thermal model describing heat transfer to or from large vessels is based on heat transfer coefficient derived from analytical solutions of forced convection in cylindrical ducts. A finite difference algorithm developed in our previous study is used to solve this complex problem with phase change heat transfer in biological tissues embedded with large blood vessels. Numerical computations are then performed to predict the transient temperature distributions of tissues under three different configurations of cryoprobe. The results indicate that different configurations of cryoprobe can produce significantly different temperature profiles and blood vessel heating in cooled tissues. Results of this study should be considered in the strategy for an optimal placement of cryoprobes when performing cryosurgical treatments in the vicinity of large blood vessels. PMID- 17282224 TI - The cryopreservation of a tissue engineered dermal replacement by programmed freezing. AB - Long-term storag of engineered bio-artificial tissues is required to ensure the off-the-shelf availability to clinicians due to their long production cycle. Cryopreservation is likely the choice for long-term preservation. This study investigated the effects of dimethyl sulfoxide (DMSO) concentrations, cooling rates, cryoprotectant medium treatment methods and seeding on the cell viability of a tissue-engineered dermal substitute. The dermal fibroblast was cultured on a polyglycolic acid (PGA) scaffolding at 37degree C and a 5% CO2atmosphere for 14 days, and dermal slices (10×3×1.5mm) were used in the experimental group. The freezing was carried out in a computer controlled programmable freezer at 0.5degree C/min, 1degree C/min and 2degree C/min in1.4M, 2.1M and 2.8M DMSO from 4degree C to -60degree C and then plunged into the liquid nitrogen tank immediately. After 24th of cryopreservation, the samples wereped in removed from liquid nitrogen and placed at room temperature in air for 0.5-1min, prior to submergence in a water bath at 37 degree C. viability of fresh control and cryopreserved dermal slices were determined with our modification of the MTT (3-[4,5-Dimethythiazol-2-yl] -2,5-diphenyltetrazolium bromide) assay. The effects of two cryoprotectant medium treatment methods and seeding (at -7degree C)on cell viability were also assessed. A cryopreservation protocol of 1degree C/min in 1.4M DMSO from 4degree C to -60degree C, and seeding at -7degree C proved optimal for this tissue-engineered dermal replacement, provided the dermal slice was transferred into the cryopreservation bag containing 1mL 1.4M DMSO bag and hold for 15min at 4degree C prior to freezing. PMID- 17282226 TI - Highly effective in vivo gene transfection by blocked star vector. AB - Nano-structured four branched, blocked star vector (BSV) was molecular designed by iniferter-based photo-living radical copolymerization method of N,N dimethylaminopropylacrylamide and then N,N-dimethylacrylamide from four dithiocarbamate-derivatized benzene for a novel gene derivery non-viral vector. The conjugated pDNA complexes were satisfactorily stable in the condition of the electrophoresis. Under the charge ratio of 5/1 (vector/pDNA), complexes of BSV and pDNA (BSV-pDNA) demonstrated satisfied transfection efficiency into COS-1 cells with a little cytotoxicity. Mice injected with BSV-pDNA polyplexes showed a higher level of gene expression in either liver, kidney or spleen using the optimal charge ratio as determined in in vitro. These results suggest the potential use of BSV as a non-viral vector in clinic. PMID- 17282225 TI - Self-assembling of DNA and PAMAM dendrimer. AB - The self-assembling of DNA and cationic polymers are of interest for their biological applications. In this paper, the interaction of DNA with PAMAM was studied by agarose gel electrophoresis, size and zeta-potential measurements and circular dichroism (CD) spectroscopy. DNA was shown to form stable complexes with PAMAM by gel electrophoresis. The mean particle size of the complexes was in the range of 150-180 nm. The zeta-potential was positive and increased with an increase of N/P ratios. Compared to naked DNA, CD spectra of complexed DNA was changed and had a decreased intensity at 270nm. High salts and excessively low or high pH values could also result in decreased CD signals of PAMAM complexed DNA. These results provide some instructions for assembling of DNA as well as gene therapy applications. PMID- 17282227 TI - Quantum dots as phototoxic drugs and sensors of specific metabolic processes in living cells. AB - When conjugated to CdSe/ZnS nanocrystals (quantum dots), the nucleobase adenine and the neurotransmitter dopamine quench fluorescence emission from in a manner strongly dependent upon the size of the quantum dot. The degree of quenching serves to predict the efficiency with which the conjugates are able to enter living cells. Along with quenching, the presence of specific receptors on the cells is necessary for QD binding, entry, and phototoxicity. Toxicity is manifested by opening of large membrane pores and by oxidative DNA damage, and does not require the release of Cd+2. In bacterial cells, light exposure is necessary for uptake, and procedures to reduce toxicity eliminate labeling. In mammalian cells, antioxidants prevent toxicity but not QD uptake, leading to QD-loaded cells that are nonfluorescent before light exposure. These findings provide a general procedure for rational design of nanoparticle-based photosensitizing drugs and for "off-on" fluorescent labels. PMID- 17282228 TI - Visualization and characterization of drug carrier transportation and distribution in vivo. AB - Micro/nano-particle drug delivery systems are being developed for improving therapeutic effects. However, most studies can only evaluate the delivery properties by indirectly measuring the pharmacokinetic changes of the drugs. It had been difficult to directly assay the drug carrier status and distribution in vivo. We described here a method using intravital microscopy to visualize individual drug carriers traveling through blood vessels. The transportation and extravasation process of these particles were monitored. The in vivo distribution patterns were also confirmed by fluorescence microscopy studies of the various tissue samples. PMID- 17282229 TI - Generation of nanostructures of mica supported lysozyme and lysozyme-nanogold conjugates by diving tip nanowriting. AB - Nanostructures of lysozyme molecules and lysozyme-nanogold conjugates were generated by atomic force microscopy in contact-, tapping- and force-distance- mode on mica in aqueous solution. In contact mode at high ionic strength, adjusted lysozyme concentration and lower loading force a monolayer of defined structure and orientation of lysozyme can be formed by the scan process of the tip. A lateral resolution of the monolayer of about 80 nm could be achieved. At larger loading forces besides a lysozyme monolayer also 3D- aggregates could be generated in parallel. In force-distance mode the volume of 3D-aggregates was studied as function of lysozyme concentration, loading force and number or frequency of up- and down-movement of the tip. Also in tapping mode 3D-aggregates were generated at the selected incubation conditions. Application of the linescan mode for solutions of nanogold or lysozyme-nanogold conjugates allowed the formation of monlayers of linear shape with lateral resolution of about 35 nm on mica. Nanogold line-structures could be connected to macroscopic gold contacts. It is postulated that adjustment of electrostatic interaction between lysozyme and substrate and the applied loading force is critical for monolayer formation. Different to the underlying mechanism of the well-established dip-pen nanolithography (DPN) (Piner et al., 1999) for the presented method of diving tip nanowriting (DTN) adsorption of the molecules from the aqueous bulk phase to the tip and thereafter the flow to the mica surface is discussed. DTN could be used to either contact proteins electrically or to form preaggregates for protein crystallization (Wiechmann et al. PMID- 17282230 TI - Novel microarray technology for post-genomic studies. AB - There are great challenges of developing high-throughput analytic tools in the post-genomic era. The microarray technology, as one of the most poowerful high throughput tools, has a lot of opportunities in meeting increasing enormous demands in the discovery of the molecular mechanisms of life systems. A number of the new concept microarrays will be developed and used in fundamental and medical researches in the near future. We developed several kinds of the new microarray chips for detecting DNA methylation patterns, double strands DNA microarray for sequence-specific DNA binding proteins (such as transcription factors), the PCR procduct microarray for screening disease related SNPs, a cap-array assay (lab-in a-tube system), and quantitative detection microarray for mulit-viruses detection and clinical applications. In this presentation, I will give brief introductions on these biochip platforms developed in our laboratory recently. Our results show that the innovations in high-throughput tools could be promoted through the combination between life science and engineering researches. PMID- 17282231 TI - BioImplantable Bone Stress Sensor. AB - The clinical management of skeletal trauma and disease relies on radiographic imaging to infer bone quality. However, bone strength does not necessarily correlate well with image intensity. There is a need for a safe and convenient way to measure bone strength in situ. This paper presents a new technique to directly measure bone strength in situ at a micro-level scale through a MicroElectroMechanical System (MEMS) sensor. The proposed MEMS stress sensor comprises an array of piezoresistive sensor "pixels" to detect stress across the interfacial area between the MEMS chip and bone with resolution to 100 Pa, in 1 sec averaging. The sensors are located within a textured surface to accommodate sensor integration into bone. From initial research, surface topography with 30 60 μm features was found to be conducive to guiding new cell growth. Finite element analysis has led to a sensor design for normal and shear stress detection. PMID- 17282232 TI - Enhancement of an electroporation system for gene delivery using electrophoresis with planar electrodes. AB - We developed a new electroporation system, including a microchip and a logic circuit, and combining with the function of electrophoresis, which can site specific enhancement of the gene concentration. We have demonstrated that the electroporation microchip could enhance and target in vitro gene transfection for cell lines. In this micro-device, the outer electrodes could provide the electrophoresis function for DNA attraction, and the inner electrodes could provide appropriate electric fields for the electroporation on the chip surface. The electrostatic force can be designed into specific regions, where the DNA plasmids are attracted to provide the region-targeting function. This study successfully demonstrates that the electrostatic force can attract DNA plasmids to the cell surface and highly enhance the gene delivery. Experimental results showed that the efficiency of gene transfection with an attracting-electric field become much higher than that without an attracting-electric field. Furthermore, the adherent cells could be manipulated in situ without detachment by this EP microchip. The system has several advantages of portable, cost-effective, high transfection rate and easy operation. PMID- 17282233 TI - Surface-Micromachined Neural Sensors with Integrated Double Side Recordings on Dry-Etch Benzocyclobutene(BCB) Substrate. AB - a neural sensor with novel structure and capable of double side recordings has been designed and fabricated using surface micromachining technique. Dry-etch Benzocyclobutene (BCB) was selected as the substrate and packaging material for its excellent electrical, mechanical and thermal properties. Positive photoresist (AZ4620) was used as the sacrificial layer during the formation of backside recording sites, and the lift-off process combined with BCB dry etch technique was developed to open the recording sites on the backside. The finished device has intracortical recording sites on both sides, and also epidural recording sites on the front side. The total channel number doubled compared to that of single side electrode structure. Three dry-etch BCB layers were applied to insulate the front side conduction traces from the backside trace layer, and package the entire devices. The developed process shows reliable and high fabrication yield, and results suggest that this newly developed neural sensor could improve the performance and efficiency of neural recording. PMID- 17282234 TI - Droplet-based Microtexture Biochip System for Triglycerides and Methanol Measurement. AB - A droplet-based microfluidic system was developed for biochemical assays of triglycerides and methanol as potential applications in medical rapid diagnostics and food safety. We present a novel platform to manipulate biology reaction droplets with features of self-moving, self-mixing, and self-positioning toward the detection spot. The driving force comes from the gradient of surface tension force generated by the hydrophobic microtexture PDMS surface. We also demonstrate the experiments in water, and blood droplets running uphill to overcome the gravity. These findings support the ongoing works to develop the multifunctional biosensors in medicine and food safety. PMID- 17282235 TI - Detection of Vesicular Stomatitis Virus using a Capacitive Immunosensor. AB - This paper describes the detection of Vesicular Stomatitis Virus using a novel capacitive immunosensor technology, whereby the respective antibodies for the antigens were used as a means for chemical detection on separate sensors. Devices were fabricated using standard etching and metal plating techniques, followed by immobilization of antibodies. Detection of antigen was performed by measuring voltage change due to changes in capacitance as antigen bound to the antibody surface. Capacitance changes were detected upon binding of specific antigen to the surface. This rugged, prototype device detected VSV down to the 2 pg/ml range. PMID- 17282237 TI - From Codabar to ISBT 128: Implementing Barcode Technology in Blood BankAutomation System. AB - Barcode technology has been widely employed in medicine and healthcare industry. In this paper, it firstly introduces the application of barcode technology in information automation system oriented to blood banks and other transfusion facilities. In the following, the label paradigm of Codabar in Macao Blood Transfusion Center (CTS-Macau) is examined through the comparison with ISBT 128, an international barcode and labeling standard for blood and blood products. And then, it tries to exemplify the supersedure of Codabar by ISBT 128 via the implementation of barcode labeling system at CTS-Macau. This paper is intended to serve as a reference of implementing barcode technology in blood bank automation system. PMID- 17282236 TI - Phase Detection of the Two-port FPW Sensor for Biosensing. AB - In this study, we provided a comprehensive methodology for designing and integrating miniature system in the biosensor application. In general, the network analyzer is commonly used for acoustic wave sensor measurement. However, it is remarkably inconvenient for portable use. Therefore, we presented a readout concept, which was focused on the miniaturization of the flexural plate wave (FPW) sensor system by integrating phase detection circuit. The miniature system includes a Wien-Bridge oscillator, a voltage following, a FPW device, a phase locked loop, a phase detector, a MCU, and a LCM display. This work succeeded in integrating all the subsystems. And the core technology of the system is the phase detection function. The results showed the phase shift resolution is 10 mV/1°. PMID- 17282238 TI - A Dynamic Blood Information Management System Based on RFID. AB - As a patient and recipient of a blood transfusion, it is important for him or her to receive the safest blood possible. Information about the donated blood should be under the track to guarantee the quality of the blood source. In this paper, we present a RFID-based blood information management system that aims at ensuring the quality of the blood and increasing the efficiency of operation management. In this system, the fingerprint sensor is adopted to enable the process of identifying blood donor more reliable and credible and RFID tag is used to make the management more convenient. In addition, GPRS is applied in this system so that real-time data can be transmitted between the bloodmobile and blood center through wireless Internet. PMID- 17282239 TI - Integrating all medical records to an enterprise viewer. AB - The idea behind hospital information systems is to make all of a patient's medical reports, lab results, and images electronically available to clinicians, instantaneously, wherever they are. But the higgledy-piggledy evolution of most hospital computer systems makes it hard to integrate all these clinical records. Although several integration standards had been proposed to meet this challenger, none of them is fit to Chinese hospitals. In this paper, we introduce our work of implementing a three-tiered architecture enterprise viewer in Huzhou Central Hospital to integration all existing medical information systems using limited resource. PMID- 17282240 TI - The design of formatted report language and its applications in medical information systems. AB - The extensible markup language (XML) is gaining attention in medicine because of its flexibility. Since most XML documents convey information only on content, it has been difficult for medical applications to present and edit them in the precise format, as required in many clinical circumstances. This article offers a design of formatted report (FR) language to meet almost all medical-oriented requirements of presenting and editing data items such as text, image, scheme and video in the precise format. As FR language could be converted to and from other XML-based languages, it's suitable for almost all XML application environments. A set of components and tools have also been built to promote the application of FR language in the medical fields. These components and tools have established a development platform and could cover almost all application fields of XML. The FR language together with the set of components and tools has already been used in image diagnostic system to present and edit image report in the clinical environment. PMID- 17282241 TI - A Workflow Based Self-care Management System. AB - Designing and developing computer-based self-care tools faces challenges for modeling self-care decision making processes and monitoring self-care activities. In this paper, a simplified conceptual model for self-care decision making is presented and a workflow based self-care management system is proposed to implement the process-oriented monitoring. Self-care knowledge of specific conditions is derived from consumer guidelines. Consumers' preferences on self care are taken into consideration through the customization and implementation of the hierarchical self-care workflow. An application of workflow based self-care management system in the implementation of dermatology diagnosis and self-care tool (DDST) is also discussed. The proposed methodology of workflow based self care management provides the potential for information integration between computer-based self-care tools and hospital information systems. In addition, the detailed self-care records obtained from the workflow management system make it possible for quantitative analysis of self-care activities and critical evaluation of the effect of computer-based self-care tools on healthcare outcomes. PMID- 17282242 TI - HIPPA's compliant Auditing System for Medical Imaging System. AB - As an official rule for healthcare privacy and security, Health Insurance Portability and Accountability Act (HIPAA) requires security services supporting implementation features: Access control; Audit controls; Authorization control; Data authentication; and Entity authentication. Audit controls proposed by HIPPA Security Standards are audit trails, which audit activities, to assess compliance with a secure domain's policies, to detect instances of non-compliant behavior, and to facilitate detection of improper creation, access, modification and deletion of Protected Health Information (PHI). Although current medical imaging systems generate activity logs, there is a lack of regular description to integrate these large volumes of log data into generating HIPPA compliant auditing trails. The paper outlines the design of a HIPAA's compliant auditing system for medical imaging system such as PACS and RIS and discusses the development of this security monitoring system based on the Supplement 95 of the DICOM standard: Audit Trail Messages. PMID- 17282243 TI - Development and Validation of a 3D Clinostat for the Study of Cells during Microgravity Simulation. AB - The clinostat was originally used to find out why plant roots appear to grow predominantly toward the center of the Earth. Over the last 2-3 decades, slow- and fast-rotating 2D and 3D clinostats have been used to assess cellular adaptation to this environment. A cell culture is placed in a spin module of the clinostat platform and its rotation is set empirically (2-3 rpm). The machine is then allowed to run for a specified period (hours to days) after which the cultures are removed and assayed for specific properties, such as cell growth, size and shape, distribution of receptors, integrity of the cytoskeleton or gene expression. A 3D clinostat was developed by the Microgravity Laboratory/IPCT PUCRS group and validated by the Stem Cell Group of Kingston University London, which used 4 different types of human cancer cells and cord blood stem cells (CBSC). After rotation for 19h at 37degC, 5%CO2 humidified atmosphere, the 3D clinostat significantly improved proliferation potential of all tested cell populations when compared to static cultures. After only 5 days, high definition microscopic analysis revealed that all CBSC adhered and expanded onto the BDtrade 3D collagen composite scaffolds, and cross-developed into hepatocyte-like cells upon stimulation. PMID- 17282244 TI - Effects of muscle electrical stimulation on bone mineral density in the hindlimb bones of the tail-suspended rats. AB - Bone mass loss caused by microgravity is considered as one of the worst influences to human body during long-term spaceflight. As one of the countermeasures to retain bone mass, muscle electrical stimulation is just started in spaceflight application and needs further research. This work is aimed to investigate the effects of muscle electrical stimulation based on the tail suspended rat experiment. The statistical results of bone mineral density have shown that muscle electrical stimulation can retain bone mass to a certain extent under the condition of simulated microgravity. PMID- 17282245 TI - Real-Time, Automatic Detection Of A Small Biomolecule Using The Novel Portable On line Biomolecules Analyzer. AB - Previous studies have shown that combined stresses in space flight can affect astronauts' health. On-line monitoring biochemical markers in body fluids which are highly related to some kinds of diseases is a practical method used as the health early alarm and medical care system for astronauts. In this study, a portable on-line biomolecules analyzer (POBA) was developed and utilized for the assay of 2,4-Dinitrophenylhydrazine(DNPH), which offered a portable model for the measurement of low-molecular-weight biochemical markers in body fluids at real time. PMID- 17282246 TI - Integrating telemonitoring with clinical information systems: a case study. AB - Current health scenarios have witnessed increased attention for home care as a way to enhance the quality of service provision and reduce costs. In recent times, clinical information systems (CISs) have undergone significant development and they now include useful applications for doctors, nurses and other health professionals. The present work investigates the possible integration of a home based telemonitoring system within a CIS to enhance its potentials. Test results showed a smooth integration and highlighted multiple advantages such as use of a single interface for the management of several data types, inclusion of health related data about in-hospital and home periods, workflow creation and check points during home care provision, use of consistent criteria for data security and privacy protection. PMID- 17282247 TI - Design and implementation of internet based healthcare robot system. AB - with the increase of aging people, the task to maintain the health care level becomes heavier. To compensate for shortages of nurses and reduce the stress of nursing work, we have attempted to create an Internet based mobile robot system for hospitals or home healthcare. In this paper, we described a feasibility study and a basic platform design of a teleoperated healthcare service system via the Internet. We started from a literature review in the research on this topic. We then presented HSR-I, a new modular platform for Internet based mobile robotic systems including design principles, hardware and software architecture. Field tests at hospital facilities have confirmed the effectiveness of the proposed system equipped with the capability for navigation by visual information and friendly human-robot interface. PMID- 17282248 TI - Monitoring and Transmission via Wireless Network for an Assistive Device. AB - Owing to the increasing number of disabled individuals, technical aids are acting more aggressively in the era of modern medicine. The M3S (Multiple Master Multiple Slave) system developed for the physically challenged, utilizes intelligent transmission and integration mechanisms to arrange all hooked-up devices with proper control. To overcome certain limitations of the system (e.g. distance), an RF (Radio Frequency) wireless module would be in charge of the wireless communication between a remote bus and a local bus. It is demonstrated here as assistance for parking assistive vehicles (e.g. powered wheelchair) located in a remote region, which also includes monitoring and usage of accessorial data transmissions shown in our man-machine interface. PMID- 17282249 TI - Tele-therapy system for cognitive disturbances. AB - Stroke can cause a variety of cognitive disturbances depending on the location of the injury. It is proved by clinic that some specific cognitive training is a safe and effective method for stroke patients who are suffering from cognitive disturbances. In this paper, we designed and implemented a tele-therapy system that based on Internet, so that the patients with cognitive impairment can take the therapy at home. It might be more convenient and effective than the traditional therapy of outpatient visits to the rehabilitation hospital. The tele therapy system is composed of the computer-assisted cognitive training system (CACT) and the tele-therapy web on Internet for managing the system and training records. PMID- 17282250 TI - Detection and Classification of Movements in Bed using Load Cells. AB - The quality of our life is tied to the quality of our sleep. People with sleep deficits may experience impaired performance, irritability, lack of concentration, and daytime drowsiness. Increased mobility in bed can be a sign of disrupted sleep. Therefore, body movements in bed represent an important behavioral aspect of sleep. In this paper, we propose a method for detection and classification of movement that uses load cells placed at each corner of a bed. The detection of movements is based on short-term analysis of the mean-square differences of the load cell signals. Movement classification is based on features extracted from a wavelet-based tiresolution analysis (MRA) to classify the type of movement into two classes: small and large. A linear classifier is trained on each level of the MRA, and the decisions of the 4 classifiers are combined using a Bayesian combination rule. The method is evaluated on load cell data collected from 6 subjects. Each subject performed 5 trials composed of 20 pre-defined movements including small shifts of position to large movements of torso and limbs. The performance measure for the detection problem is the equal error rate (EER). We show that the detection method achieves a 2.9% EER and that the classification method has a classification error of 4%. PMID- 17282251 TI - Evaluation of patient-centered electronic health record to overcome digital divide. AB - Advances and wide acceptance of information and communication technology (ICT) have made development and implementation of web-based electronic personal health records (PHRs) more feasible than ever before, and previous studies have demonstrated some of its potential and promises. However, this type of ICT dependent approach inherits its own vulnerabilities of exposing the society to "digital divide", commonly described as the gap that exists among individuals and communities with regards to the 'haves' and 'have-nots' of information and modern communications technologies. To address these concerns and improve healthcare outcomes, we have developed and customized a web-based patient-centered electronic PHR, named the Personal Health Information Management System (PHIMS), and evaluated the system at the Everett Housing Authority, which provides housings for low-income families and elderly or disabled populations. A preliminary study demonstrates that 92% of the participating residents are satisfied with the PHIMS system in general. Some of the residents found PHIMS records very useful for their clinic visits. PMID- 17282252 TI - Effect of prolonged pressure on flowmotion: An Investigation Using an in vivo Rat Model. AB - The objectives of this study is to assess the effect of prolonged loading on the skin blood flowmotion in rats as measured by Laser Doppler flowmetry (LDF) using wavelets transform and power spectral in the rat skin microcirculation. External pressure of 13.3kPa (100 mmHg) was applied to the trochanter area and the distal lateral tibia of Sprague-Dawley rats via two specifically designed pneumatic indentors. The loading duration was 6 hours/day for 4 consecutive days. The results showed that 1) spontaneous rhythmic activities were present in skin blood flow of anesthetized rats, 2) significant decrease of flowmotion power (p=0.023 for trochanter and p=0.043 for tibia) was found in the frequency range of 0.01 0.04Hz after prolonged loading. Our results suggested that reduced vasomotion in the frequency of 0.01-0.04 Hz might be involved in the mechanisms leading to pressure ulcer formation. PMID- 17282253 TI - Characterization of arterial wave propagation and reflection in mice. AB - Wave propagation through the arterial system changes with age and disease state, and mutant mice are often used to study these conditions. We have developed several noninvasive ultrasonic techniques to measure blood velocity and vessel wall motion from which we can calculate aortic pulse wave velocity (PWV), local compliance, impedance spectra, characteristic impedance (Zc), augmentation index (AI), and forward and backward waves in intact anesthetized mice. We found altered vascular mechanics in many mutant strains of mice. In old mice PWV, AI, and Zcare increased. In atherosclerotic mice PWV, Zc, and AI are increased; peripheral resistance and arterial compliance are decreased; and wave reflections are enhanced. We find that the initial deceleration of carotid velocity is caused by peripheral reflections, and that increased acceleration of velocity in the aortic arch in atherosclerotic mice is caused by enhanced carotid reflections returning to the heart and traveling forward in the aorta. We conclude that when scaled for heart period, the mouse arterial system and its responses to age and disease are similar to those in man. The ability to evaluate arterial mechanics in mice will expand their use as models to study human arterial diseases and conditions. PMID- 17282254 TI - Is aortic impedance altered in dwarf mice? AB - Dwarf mouse (deficient in growth hormone and insulin-like growth factor-1) lives about 30% longer than wild type mice. However, very little is known about their cardiovascular physiology. We examined the aortic input impedance in dwarf mice and their wild-type littermates to evaluate any differences. Aortic impedance was determined using pressure and velocity signals which are independent of body size. Significant differences were observed in the body weight, aortic systolic, diastolic and mean pressures, and peak and mean aortic flow velocities. No differences were observed in impedance parameters of peripheral resistance, impedance at first harmonic, and characteristic impedance between the two groups. However, the impedance curve in the dwarf mice was higher at low frequency and decreased gradually with increasing frequencies but in the wild type mice the impedance curve oscillated around the characteristic impedance. PMID- 17282255 TI - A Model-based Numerical Analysis in the Early Development of Intracranial Aneurysms. AB - Hemodynamic stresses are known to degenerate the arterial wall and be involved in the pathogenesis of intracranial aneurysm formation and development. The present study simulates the formation and growth of aneurysms by focusing on the interplay between the wall shear stress, degeneration of the mechanical wall properties, and the wall deformation. We construct numerical aneurysm models arisen from both straight and curved arteries, and we hypothesize that high local wall shear stress larger than a certain threshold value will lead to a linear decrease in the mechanical property of the vessel wall. The degeneration of vessel wall leads to wall deformation and redistribution of the wall shear stress, which in turn leads to further degeneration of the wall. Development of aneurysm is observed in both the straight and curved models. In the straight model, the growth of aneurysm is small and mainly at the distal neck region, and the aneurysm stops growing after several steps. In contrast, in the curved model, the aneurysm continues to grow in height and width. Our computer simulation shows that even if the wall shear stress inside a saccular aneurysm is low, aneurysm development can occur due to degeneration of the wall distal and proximal to the aneurysm. The interaction between the geometry change and the wall degeneration is key to the development of aneurysms. The method demonstrates the potential utility of model-based numerical methods in the investigation of developmental biology of intracranial aneurysms. PMID- 17282256 TI - In-vitro Experimental Validation Of Hemodynamics Study For Proximal Anastomosis Models. AB - Hemodynamics is widely believed to correlate with the stenosis of coronary artery bypass graft (CABG). Although some researchers had investigated distal anastomosis, further studies upon the proximal anastomosis are still necessary as the initiation and growth of the stenosis process may be influenced by the nature of the flow at the proximal anastomosis. Therefore in this project, flow characteristics of proximal anastomosis models were studied numerically in order to enhance the understanding of the stenosis pathophysiological process and particle image velocimetry (PIV) measurements were also carried out to validate the numerical simulation results. Two models (viz. 90deg and 135deg anastomotic models) were firstly designed to mimic the proximal anastomosis of CABG for left and right coronary arteries respectively. A fair match between numerical and experimental data was observed in terms of flow characteristics, velocity profiles and WSS distributions under physiological flow conditions. The overall difference between their velocity profiles ranged from 8% to 54%. It is evident from the findings that PFV measurement can obtain quantitative results as accurate as LDA and numerical simulation is able to provide much detailed information with enough mesh density. In addition, the 135deg model would result in better patency rate based on hemodynamic analysis. PMID- 17282257 TI - Influence of aorto-left coronary bypass graft geometry on wall shear stress distribution. AB - Idealized geometries of bypass grafts have been constructed to analyze the blood flow in an aorto-coronary bypass graft system. In this paper we discuss the influence of the realistic bypass graft geometry for the in-plane and out-of plane aorto-left bypass graft models on the wall shear stress distribution. In the in-plane aorto-left coronary bypass graft model we have the centerlines of the aorta, the left coronary vessel and the bypass graft to lie in the same plane (planar geometry) where as in the out-of-plane model the centerlines of the vessels no longer lie in a constant plane (non-planar geometry). Computational fluid dynamic (CFD) studies are carried out using the commercial software FLUENT. It is known that the coronaries are well perfused during the diastole and hence even though simulations are performed at different instances (both the systole and diastole phase) of the cardiac cycle, we have demonstrated the wall shear stress distribution in the distal anastomotic section for both the models at two specific instances of the diastolic phase, namely, early diastole (t=0.45 s) and mid-diastole (t=0.7 s). Our results reveal that in comparison to the in-plane model, the wall shear stress magnitude in the out-of-plane model is greatly reduced at the bed of the anastomosis. Thus a subtle change in the geometry can affect the flow field significantly that may promote graft patency. PMID- 17282258 TI - Cooling and shielding systems for infrared detectors - requirements and limits. AB - This paper presents three main cooling systems used for infrared detectors. At first thermoelectric devices are discussed. They allow cooling down the detector with low efficiency and not to the very low temperature. They do not generate any vibrations and therefore are suitable for thermal detectors, where the microphone effect can decrease their performance. Photon detectors need to be cooled down even to 77K or better. The only way to have such deep cooling is to use the cooler based on thermodynamic cycle such as Stirling one. With the high efficiency one can easily obtain cryogenic temperature for a detector. The electromagnetic noise and vibration generation are the main disadvantages of using such devices. Joule-Thomson effect during gas expansion is 3rdcooling system discussed in the paper. It is highly effective process, used for gas liquefaction too. The working gas is being removed during cooling into the atmosphere, so the need of continuous supplying with compressed one, what makes this system very difficult for remote applications. In the paper, simple calculations are presented to illustrate the advantages and disadvantages of the different cooling systems. PMID- 17282259 TI - A Novel Approach of Analyzing the Relation between the Inner Heat Source and the Surface Temperature Distribution in Thermal Texture Maps. AB - Thermal Texture Maps is a new medical imaging technology. It can pinpoint the abnormal heat sources inside human body by using thermography analysis. Many clinical studies have confirmed its diagnostic value. The current principle is to establish the relationship between the inner heat source and the surface temperature distribution by means of thermal-electric analogy, and then the depth of the heat source is obtained by defining the half power point. Although the method produced higher effectiveness and sensitivity that supported by many clinical applications, its methodology is beyond comprehension. In this paper, we propose a novel method to deduce the depth and intensity of the inner heat source from the surface temperature distribution. PMID- 17282260 TI - Thermography in psoriasis vulgaris evaluation. AB - Psoriasis vulgaris is a chronic inflammatory skin disease with a strong genetic component, characterized by hyperkeratosis, dermal inflammatory infiltrate and increased angiogenesis. The aim of the present study was to employ thermography in evaluation of psoriatic lesions localized in different parts of the body. A series of in-patients with stable plaque type psoriasis vulgaris were included. ThermaCam INFRAMETRICS 290E thermocamera with temperature resolution of 0.1 °C was used in the study. Both visual and thermal images of 84 areas of lesional and lesion-free skin in patients were taken and analyzed. All the skin lesions were divided into 4 groups, according to their location i.e. found on the upper limbs, lower limbs, chest and back. Increased temperature was observed over psoriatic lesions located in the chest and upper limbs. To the contrary, skin lesions located on the back and lower limbs presented lower temperature. It is conceivable to speculate that lower temperature revealed within the lower parts of the body may explain to some extend slower regression of the lesions located in this region in comparison to skin lesions located over the upper parts of the body. PMID- 17282261 TI - Facial expression recognition using thermal image. AB - Facial expression recognition will be studied in this paper using mathematics morphology, through drawing and analyzing the whole geometry characteristics and some geometry characteristics of the interesting area of Infrared Thermal Imaging (IRTI). The results show that geometry characteristic in the interesting region of different expression are obviously different; Facial temperature changes almost with the expression at the same time. Studies have shown feasibility of facial expression recognition on the basis of IRTI. This method can be used to monitor the facial expression in real time, which can be used in auxiliary diagnosis and medical on disease. PMID- 17282262 TI - Visualisation of medical infrared image databases. AB - We introduce a method for visualising and navigating through a collection of medical infrared images. Multidimensional scaling is used to provide an overall picture of a given image database by projecting all images on a plane and arranging them so that images that are visually similar are placed close to each other. Navigation through the image set can then be performed by zooming into an area of interest which could correspond to images describing similar symptoms. Experimental results are provided on an image database of 200+ thermal images. PMID- 17282263 TI - Optimization of MR-Relaxometry for BMD-measurements and its Correlation with DEXA. AB - The aim of this study was to optimize MRI conventional protocols for BMD measurements using MR-Relaxometry in systems not facilitated with special multi echo protocols. Since, cortical and trabecular bone separation can not be performed in DEXA, so the results might lead to erroneous interpretation of BMD values. One method for bone quality determination is MR relaxometry that derives R2(=1/T2), R2*(=1/T2*) and R2'(=R2*-R2). This study was performed by 1.5T MRI system(Picker Vista-Q800), an uniformity phantom(1.25gr/l CuSO4, with T2=200ms for calibration), a body RF-Coil, 7 normal, 7 osteopenia, 7 osteoporosis volunteers and Lunar DEXA system(DPX-MD). To determine R2*and R2, multi GE and SE protocols with different TE/TR were used. Then in phantom and in coronal section of femoral-neck, relaxation rates were compared with BMD. The slope of neperian-logarithm of signal vs. TE in GE as -R2*used for protocol optimization. Therefore, for phantom calibration, optimized GE parameters of TE=13.42/18/26.8 ms, TR=800ms and ST=8mm used for the measurement of R2*, while, the measurement of R2 required the optimized SE parameters of TE=30/60/90/120ms, TR=800ms and ST=8mm, with CV(R2*)=2.96%, CV(R2)=3%, respectively. In volunteers for SE, TE of 36/54/63/72ms and TR=800ms were used, while, for GE the TEs/TR were the same as those of phantom study. R2*and R2' showed a significant positive correlation with BMD, r=0.62(p<0.05) & r=0.62(p<0.05) respectively. Finally, in accordance with DEXA values, the results showed that MR-Relaxometry is a proper tool for BMD-measurements in femoral-neck. Also it may be used as a complement method for DEXA failure in BMD-assessments. PMID- 17282264 TI - Dual-Modality PET-CT Visualization using Real-Time Volume Rendering and Image Fusion with Interactive 3D Segmentation of Anatomical Structures. AB - Recent advances in medical imaging have resulted in the introduction of dual modality scanners which can simultaneously acquire two independent imaging modalities, such as positron emission tomography (PET) and computed tomography (CT) image data in a single session. These multi-dimensional PET-CT data contain both the functional and anatomical information of the human body, thus, providing the ability to identify anatomical structures of interest and then overlaying the result onto the corresponding functional structure, as an example. The utilization of the combined functional and anatomical information has been proven to be an effective approach in diagnosis and interpretation of certain medical conditions. However, the increase in image dimensions has not been accompanied with new visualization techniques, with the use of two-dimensional (2D) display being the norm. In this study, we propose a new approach to three-dimensional (3D) visualization of dual-modality PET-CT data in order to complement the 2D visualization and potentially improve medical diagnosis and interpretation. We have design and implemented a prototype visualization technique using real-time volume rendering and image fusion running on a commodity graphics card. We further propose the application of interactive segmentation of 3D anatomical structures from CT data which can be used to identify the corresponding functional structure in volume visualization. PMID- 17282265 TI - The role of three-dimensional visualization in surgical planning of treating lung cancer. AB - This paper presents a study on investigating the role of three-dimensional visualization (3-D displays) in surgical planning of treating lung cancer. Contrasting to the minor role of 3-D displays in learning anatomy, this study discovered a significant role of 3-D displays in this surgical planning. The study proved the concept that 3-D displays of lung cavities are feasible and have distinctive advantages over two-dimensional views of computed tomography in decreasing workload by about 50%, reducing planning time by about 30%, and increasing the accuracy of predicted resectability by about 20%. These results forecast benefits for employing 3-D displays in surgical treatment of lung cancer, once the technique is perfected. PMID- 17282266 TI - Preliminary Study for Automated Recognition of Anatomical Structure from Torso CT images. AB - The anatomical human structure recognition is very important and necessary during the development of computer-aided diagnosis (CAD) system. In this paper, we propose an image processing scheme that can recognize the general structure of human torso by identifying the human torso region from CT images automatically and separating it into 7 parts: skin, subcutaneous fat, muscle, bone, diaphragm, thoracic cavity and abdominal cavity based on CT number distribution and spatial relations between different organ and tissue regions. We applied this scheme to 313 patient cases of torso CT images and confirmed its usefulness from the preliminary experiment. PMID- 17282267 TI - Interactive tooth segmentation of dental models. AB - The accurate segmentation of the teeth from the triangle mesh is an important step in computer-aided orthodontic. Because teeth come in different shapes and their arrangements vary substantially from one individual to another, tooth segmentation is difficult. This paper proposes a new method to accurately segment the teeth interactively. Based on curvature values of the triangle mesh, feature points are connected to feature regions. After feature lines are extracted from regions, feature contour can be obtained with the help of user supplied information. Using feature contour, the tooth are segmented accurately and individually. PMID- 17282268 TI - 3D Visualization of Echocardiogram and Blood Flow. AB - Congenital heart defect is a leading cause of children mortality. Two-dimensional echocardiography is a safe and noninvasive diagnostic tool and two-dimensional images can be reconstructed to a three-dimensional model. However, for some complex congenital heart diseases, the visualization of three-dimensional cardiac tissue structure alone is not enough. Visualization of blood flow patterns in a human heart is important to evaluate cardiac disease of patients. Color flow imaging is a well-established ultrasound mode and very valuable for visualizing the distribution of blood flow in a specific region of interest. However, blood flow patterns in a human heart have three-dimensional complex structure and change dynamically, but the output of color flow imaging is usually presented as a two-dimensional image on a cross section of a heart. The authors make use of an echocardiography system to acquire the data which include cardiac tissue structure and blood flow patterns, and construct an interactive visualization system for the three-dimensional heart and blood flow. With the visualization system, which possesses interactivity and a changeable view, users can easily understand the inner cardiac structure and blood flow in the heart. The images that we use are not only from actual patient data, but also from isolated porcine hearts and hearts of living dogs. PMID- 17282270 TI - Optical biosensors for monitoring dynamic mass redistribution in living cells mediated by epidermal growth factor receptor activation. AB - This paper reported the identification and mechanism of dynamic mass redistribution in living cells mediated by epidermal growth factor receptor (EGFR) activation using resonant waveguide grating (RWG) biosensors. In response to epidermal growth factor (EGF) stimulation, human epidermoid carcinoma A431 cells gave rise to a dynamic response due to dynamic mass redistribution (DMR) in the cells. The DMR response was strongly dependent on cell culture conditions and EGF concentrations. The DMR response of quiescent A431 cells was found to be saturable to the concentration of EGF, and was able to be fully suppressed by a specific and potent EGFR tyrosine kinase inhibitor, AG1478. The effect of various known inhibitors/drugs on the DMR response of quiescent A431 cells clearly showed that the EGF-induced DMR involves the Ras/mitogen-activated protein (MAP) kinase pathway, and mainly proceeds through MEK. The DMR signatures obtained here offer integrated quantitative and dynamic representation of EGFR activation and can be used to screen modulators that can regulate critical targets in both the upstream and the downstream EGFR signaling pathways. PMID- 17282269 TI - Slice-Based Prostate Segmentation in 3D US Images Using Continuity Constraint. AB - In the diagnosis and therapy of prostate cancer, it is critical to measure the volume of the prostate and locate its boundary. Three-dimensional transrectal ultrasound (3D TRUS) imaging has been demonstrated to be a useful technique to perform such a task. Due to image speckle as well as low contrast in ultrasound images, segmentation of the prostate in 3D US images is challenging. In this paper, we report on the development of an improved slice-based 3D prostate segmentation method. First, we imposed a continuity constraint for the end points of the prostate boundaries in a cross-sectional plane so that a smooth prostate boundary in 2D is obtained. Then, in each 2D slice, we inserted the end points into the vertex list of the initial contour to obtain a new contour, which forces the evolving contour to be driven to the boundary of the prostate. Evaluation demonstrated that our method could segment the prostate in 3D TRUS images more quickly and accurately. PMID- 17282271 TI - Non-invasive monitoring of human cerebral oxygen saturation by near infrared spectroscopy: instrumentation, calibration and application in cardiopulmonary bypass. AB - Cerebral oxygenation especially regional cerebral oxygen saturation (rSO2) needs to be monitored to avoid irreversible damages induced by hypoxia. Based on steady-state spatially resolved spectroscopy (SRS), rSO2was obtained by the NIRS oximeter developed by our group. The oximeter was calibrated by blood gas analyzer using the liquid tissue model made up by our group. The results indicate that the correlation between rSO2and the real oxygen saturation of the model is excellent (R>0.99), and the influences by the background absorption and overlaying tissues are little. The rSO2of 14 patients were monitored during cardiopulmonary bypass (CPB) non-invasively by our oximeter. The results indicate that first, NIRS is almost the only available method to monitor rSO2non-invasively during CPB; second, rSO2is negatively correlated with body temperature and positively with blood perfusion rate, so it reflects the balance between cerebral oxygen supply and consumption; third, the low perfusion rate stage and the rewarming stage are relatively critical because rSO2decreases significantly and may be relatively low. PMID- 17282272 TI - The establishment of an automatic separation system for marine meiobenthos. AB - Research of the marine meiobenthos is of great value in the marine ecology and the marine mineralogy. At present, picking up meiobenthos from the sedments manually under microscope is still prvalent in spite of the large consumption of human power and time. So that in this paper, an automatic separation system was established. The excellent performance in separating marine meiobenthos was demonstrated by the precision of above 95%. PMID- 17282273 TI - Evaluation of a capillary measuring system for the characterisation of small tissue samples by impedance spectroscopy at higher frequencies. AB - For the gentle and non-destructive characterisation of small tissue samples, non invasive methods are required for biotechnological applications and medical diagnostics. One approach is the characterisation of small tissue samples by impedance spectroscopy using a measuring capillary. In this paper, the applicability of a capillary measuring system to record the impedance of a biological sample over a wide frequency range is evaluated using a suspension of human breast adenocarcinoma cells (MCF-7). Impedance spectra over a frequency range 1 Hz to 1.1 GHz were recorded. To describe the electrical properties of the cell suspensions, we use an equivalent circuit model containing advanced RC elements. Changes of plasma membrane integrity of suspended cells were detectable. PMID- 17282274 TI - Optimization of Off-null Ellipsometry for Optical Biosensor Applications. AB - The optimization of off-null ellipsometry is described with emphasis on the improvement of resolution for visualizing biomolecule layers. For optical biosensor with layer thickness below 6.5 nm, a numerical simulation for the dependence of resolution on the azimuth settings of polarizer and analyzer is presented first. For comparison, three different resolutions are given at three azimuth settings which are near null and far away from null condition, respectively. Furthermore, the square or linear approximation relationship between the intensity and the layer thickness are also given at these settings. The difference among their accuracy is up to 100 times or so. Experimental results of the biosensor sample verify the optimization. PMID- 17282275 TI - Review on thermal image processing for passive and active thermography. AB - In this paper, the main image processing methods used for both passive and active thermography are presented. 1st and 2nd order statistical thermal signatures are discussed. Typical methods of classification are presented. PMID- 17282276 TI - Biomedical applications of functional infrared imaging. AB - This paper introduces the reader to the functional infrared imaging, that is the application to the biomedical field of high-technology infrared imaging devices combined to the modeling of the bio-heat processes involved in the body thermoregulation. Such an approach allows defining quantitative parameters for diagnosis and monitoring. Some recent biomedical applications of the technique are then shown and explained. PMID- 17282277 TI - Noninvasive Multimodality Imaging Techniques to Assess Kaposi's Sarcoma. AB - We evaluated three non-invasive method, thermography, laser Doppler imaging and near infrared multi-spectral imaging to quantitatively assess parameters of vascularity in Kaposi's sarcoma. The KS lesion generally has increased temperature, blood velocity and blood deoxy-hemoglobin. There is a strong correlation between temperature and blood velocity (R= 81, p <0.001). After treatment with experimental drug (liposomal doxorubicin and interleukin-12), temperature, blood velocity, blood volume and deoxy-hemoglobin of the lesions are reduced from the baseline at week 18. The techniques are objective, easy to perform, and appear to be very sensitive in assessing improvement in the lesions upon administration of therapy. PMID- 17282279 TI - Imaging Breathing Rate in the CO2Absorption Band. AB - Following up on our previous work, we have developed one more non-contact method to measure human breathing rate. We have retrofitted our Mid-Wave Infra-Red (MWIR) imaging system with a narrow band-pass filter in the CO2absorption band (4.3 µm). This improves the contrast between the foreground (i.e., expired air) and background (e.g., wall). Based on the radiation information within the breath flow region, we get the mean dynamic thermal signal. This signal is quasi-periodic due to the interleaving of high and low intensities corresponding to expirations and inspirations respectively. We sample the signal at a constant rate and then determine the breathing frequency through Fourier analysis. We have performed experiments on 9 subjects at distances ranging from 6-8 ft. We compared the breathing rate computed by our novel method with ground-truth measurements obtained via a traditional contact device (PowerLab/4SP from ADInstruments with an abdominal transducer). The results show high correlation between the two modalities. For the first time, we report a Fourier based breathing rate computation method on a MWIR signal in the CO2absorption band. The method opens the way for desktop, unobtrusive monitoring of an important vital sign, that is, breathing rate. It may find widespread applications in preventive medicine as well as sustained physiological monitoring of subjects suffering from chronic ailments. PMID- 17282278 TI - Image Analysis of Breast Tumors Using Thermal Texture Mapping (TTM). AB - To explore the characteristics of thermo-source of breast tumors on Thermal Texture Maps. Compared with the histological results, thermo-source characteristics on TTM in 106 cases with breast mass, who would undergo breast surgery, were analyzed according to the parameters such as the depth, morphology, structure, and temperatures of abnormal heat foci in order to find the differences between benign diseases and malignant tumors. The coincidence rates of Thermal Texture Maps with pathological findings and the corresponding thermo eradiate values in 49 cases with malignancy and 57 cases with benign diseases were 89.5% and 91.9%, 2.599 and 1.822 (P < 0.001), respectively. The statistics differences were significant between the two groups. Contrast sharply with benign diseases, there were irregular morphology, denser structures, higher thermo eradiate values in malignant tumors. Thermal Texture Maps could be used as an important tool for the differentiation of breast diseases. PMID- 17282280 TI - Role of IR-Thermal Imaging and Electroimpedance Measurements in Medical Diagnostics. AB - This is a review of the state of the art in two important modalities - thermal and electrical properties of living tissues - that are complementary from the point of view of medical diagnostics. Advantages and limitations of IR thermal imaging and electroimpedance measurements, including tomography procedures are discussed. Properties of both modalities are compared from the point of view of skin burn evaluation, early recognition of breast cancer and some applications in cardiosurgery monitoring. PMID- 17282281 TI - Advanced technique in breast thermography analysis. AB - Thermography is a non-invasive and non-contact imaging technique used widely in the medical arena. This paper investigates the analysis of thermograms with the use of Bio-statistical methods and Artificial Neural Networks (ANN). It is desired that through these approaches, highly accurate diagnosis using thermography techniques can be established. The proposed Advanced Technique, is a multi-pronged approach comprising of Linear Regression (LR), Radial Basis Function Network (RBFN) and Receiver Operating Characteristics (ROC). It is a novel and integrative technique that can be used to analyze complicated and large numerical data. In this study, the Advanced Technique will be used to analyze breast cancer thermogram for diagnosis purposes. The use of LR will show the correlation between the variables and the actual health status (healthy or cancerous) of the subject, which is decided by using mammography. This is important when selecting the variables to be used as inputs, in particular, for building the neural network. For ANN, RBFN is applied. Based on the various inputs fed into the network, RBFN will be trained to produce the desired outcome, which is either positive for cancerous or negative for healthy cases. When this is done, the RBFN algorithm will possess the ability to predict the outcome when there are new input variables. The advantages of using RBFN include fast training, superior classification and decision making abilities as compared to other networks such as Back-Propagation. Next, ROC is used to evaluate the accuracy, sensitivity and specificity of the outcome of RBFN Test files. PMID- 17282282 TI - Biomedical nanotechnology for molecular imaging, profiling, and drug targeting. AB - Nanometer-sized particles have novel optical, electronic, and structural properties that are not available from either individual molecules or bulk solids. When linked with tumor targeting ligands such as monoclonal antibodies, these nanoparticles can be used to target tumor antigens (biomarkers) as well as tumor vasculatures with high affinity and specificity. In the "mesoscopic" size range of 10-100 nm (diameter), nanoparticles also have more surface areas and functional groups that can be linked to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents. In this article, we briefly discuss the use of bioconjugated nanoparticles for delivery and targeting of anticancer drugs. PMID- 17282283 TI - Biomedical applications based on core-shell nanoparticles. AB - Here some progresses of core-shell nanoparticles (NPs) for biomedical applications have been reported. A new synthesis mechanism for preparation of core-shell NPs by using water-in-oil (W/O) microemulsion technique has been investigated. And the applications of the core-shell NPs on cell recognition, oligonucleotide detection, single bacterial detection, pH nano-sensor for single cell, DNA recovery and gene carrier have been demonstrated. PMID- 17282284 TI - Electrostatic Self-assemble and Nanomedicine. AB - Electrostatic self-assemble (ESA), which based on the alternating physisorption of oppositely charged polyelectrolyte, appears to be a promising method in preparing nanolayer films of biopolymers and controlling the structures and properties in nanoscale. It provides great potential in surface design of nanolayer for bioactive coordinated coating for biomedical device, drug delivery systems and novel gene delivery systems. Although biomedical device developments have increased the quality and life expectancy of patients, the recognition of a foreign material by living organism is still a problem, as it often leads to a serial of adverse reactions, such as thrombus formation and complement activation, etc. The new strategies in this regard aim at surface tailoring of biomaterials in nanoscale to present different biologically activity. Self assembling of polymers has been increasingly explored for the preparation of well defined surfaces and interfaces in recent years [1]. Electrostatic self-assemble (ESA), which based on the alternating physisorption of oppositely charged polyelectrolyte, appears to be a promising method in preparing multilayer films of biopolymers [2]. The buildup of such layer is easy and the method can be used whatever the shape of the solid. The procedure may be carried out not only with linear polyions and boladiions, but also with DNA, proteins, virus, ceramics, and charged nanoparticles. Successful protein/polyion multilayer assembly provides new possibilities in the line of efforts to create a method of organizing proteins in layers and to build up such layers following ;molecular architecture' plans [3]. The method was extended to build up protein superlattices, i.e. PMID- 17282285 TI - Nanomolecular histopathology for renal tumor classification. AB - Renal tumors are classified into histopathologic subtypes based on light microscopy. Classification is important because subtypes have distinct genetic abnormalities and clinical behavior, yet is difficult because many cases have heterogeneous morphology. Thus, several molecular assays have been developed for tumor classification. Immunohistochemistry (IHC) permits correlation of molecular data with tissue morphology, but is difficult to quantify or perform in multiplex. Quantitative RT-PCR and gene expression microarrays are more quantitative, but lose morphologic information. We hypothesize that direct integration of histopathology with nanomolecular expression profiling will provide sensitive and specific data for renal tumor classification. Thus, we are developing novel IHC assays using antibodies conjugated to nanoparticle tags with surface-enhanced Raman scattering properties (SERS). Our preliminary data suggests that SERS-IHC can be performed using standard microscopic equipment, with potential for sensitive, quantitative multiplex assays on fixed tissues. PMID- 17282287 TI - Triple/Single quantum filtered sodium MRI of acute brain ischemia. AB - The effectiveness of reperfusion therapies during acute brain ischemia depends on the viability of the underperfused tissue. Specifically, when the ischemic tissue is viable reperfusion leads to improved clinical outcome. However, when the ischemic tissue is non-viable, reperfusion therapy can lead to intra-cerebral hemorrhage and/or an accelerated rate of ischemia formation. Perfusion and diffusion weighted proton MRI (DW MRI) are well-established techniques for the early detection of brain ischemia but are unable to positively establish the viability of the tissue. Tissue sodium concentration (TSC) has been shown to exhibit a linear and reversible response for many hours after ischemia onset. Because sodium accumulation in tissue is closely related to its metabolic status, we believe that the rate of TSC accumulation during evolving ischemia could provide useful information about tissue viability during evolving ischemia. In this paper, we discuss the technical details leading to the application of triple quantum (TQ) sodium MRI for the monitoring of brain ischemia. The proposed methods are then demonstrated in a non-human primate model of temporary middle cerebral artery (MCA) occlusion. PMID- 17282286 TI - Spatial and temporal hemodynamic study of human primary visual cortex using simultaneous functional MRI and diffuse optical tomography. AB - Blood oxygenation level dependent (BOLD) functional MRI and near infrared optical tomography have been widely used to investigate hemodynamic responses to functional stimulation in the human brain. In this paper, we present a complete methodology for integrating the two imaging modalities to study the underlying physiological mechanism of the hemodynamic response in primary visual cortex. Using a specially designed MRI-compatible optical probe, optical imaging was conducted using a frequency-domain near infrared spectrometer. Three-dimensional optical image reconstruction was based on diffuse optical tomography (DOT) using a perturbative approach. The sensitivity function of the forward problem was obtained using Monte Carlo simulations. From preliminary results, the spatial activation pattern of changes in deoxyhemoglobin concentration is consistent with the BOLD signal map. The patterns of oxy- and deoxyhemoglobin changes are also very similar to one another. The temporal hemodynamic response shows an increased total hemoglobin concentration, which indicates an increased cerebral blood volume (CBV) during physiological activation. PMID- 17282288 TI - Parallel MR Imaging with Accelerations Beyond the Number of Receiver Channels Using Real Image Reconstruction. AB - Parallel imaging using multiple phased-array coils and receiver channels has become an effective approach to high-speed magnetic resonance imaging (MRI). To obtain high spatiotemporal resolution, the k-space is subsampled and later interpolated using multiple channel data. Higher subsampling factors result in faster image acquisition. However, the subsampling factors are upper-bounded by the number of parallel channels. Phase constraints have been previously proposed to overcome this limitation with some success. In this paper, we demonstrate that in certain applications it is possible to obtain acceleration factors potentially up to twice the channel numbers by using a real image constraint. Data acquisition and processing methods to manipulate and estimate of the image phase information are presented for improving image reconstruction. In-vivo brain MRI experimental results show that accelerations up to 6 are feasible with 4-channel data. PMID- 17282289 TI - Estimating evolutionary rate of local protein binding surfaces: a Bayesian Monte Carlo approach. AB - To infer protein function by matching local surface patterns, an effective scoring matrix for evaluating surface similarity is critical. In this study, we develop an evolution model of binding surfaces using a continuous time Markov process. We develop a Bayesian Markov chain Monte Carlo method to estimate the substitution rates of amino acid residues with specialized move sets. We then develop scoring matrices of residue similarity specific to a functional site and show how they can be used to identify similar binding surfaces, and how such information can be used for predicting biological roles of proteins. Our method is especially effective in extracting evolutionary information from the phylogeny of sequences homologous to a protein structure, all of which may be of unknown functions. PMID- 17282290 TI - The Cancer Biomedical Informatics Grid (caBIGTM). AB - The Cancer Biomedical Informatics Grid (caBIGTM) is a new project initiated by the National Cancer Institute to create a computational network connecting scientists and institutions to enable the sharing of data and the use of common analytical tools. The emergence of genomics and proteomics high throughput technologies are creating a paradigm shift in biomedical research from small independent labs to large teams of researchers exploring entire genomes and proteomes and how they relate to disease. caBIGTMis developing new software and modifying existing software within Clinical Trials Management Systems, Tissue Banks and Pathology Tools and Integrated Cancer Research tools to manage the huge volume of data being generated and to facilitate collaboration across the broad spectrum of cancer research. PMID- 17282291 TI - Design of a genetic differential amplifier. AB - A genetic differential amplifier is made using the control elements of genes. The output mRNA level is proportional to the difference between the concentrations of two input proteins. The active element is engineered from the right operator of bacteriophage lambda. Mutations are introduced to yield the correct gain characteristic and to provide a bias level; the latter allows for the representation of negative differences. Simulation is used to aid the design process. A test circuit has been constructed. Preliminary experimental results indicate excellent results for the inverting input and lower gain for the non inverting input. PMID- 17282292 TI - Update on the pfam5000 strategy for selection of structural genomics targets. AB - Structural Genomics is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy that is medically and biologically relevant, of good financial value, and tractable. In 2003, we presented the "Pfam5000" strategy, which involves selecting the 5,000 most important families from the Pfam database as sources for targets. In this update, we show that although both the Pfam database and the number of sequenced genomes have increased in size, the expected benefits of the Pfam5000 strategy have not changed substantially. Solving the structures of proteins from the 5,000 largest Pfam families would allow accurate fold assignment for approximately 65% of all prokaryotic proteins (covering 54% of residues) and 63% of eukaryotic proteins (42% of residues). Fewer than 2,300 of the largest families on this list remain to be solved, making the project feasible in the next five years given the expected throughput to be achieved in the production phase of the Protein Structure Initiative. PMID- 17282293 TI - Biocomplexity of respiratory neural network during early maturation. AB - Previous studies in various animal models have shown that respiratory premotor and motor neurons undergo rapid changes in biochemical and bioelectric properties during the first month of postnatal life. Early in postnatal life, there is an increase in the complexity of the morphology of the dendritic tree of respiratory neurons as it changes from a bipolar to a multipolar morphology. During normal breathing (eupnea), the phrenic nerve has a slow, ramping output which reflects the orderly recruitment of phrenic motoneurons throughout inspiration when viewed in the time domain. Hypercapnia stimulates the respiratory system increasing both the respiratory frequency and amplitude. During severe hypoxia, the output of the phrenic nerve initially falls to zero and then returns with a completely different firing pattern, gasping. During gasping the phrenic nerve fires with an abrupt onset and rises rapidly to maximal neural activity with a decrementing decline. During recovery from hypoxia a variety of respiratory patterns between eupnea and gasping are seen in the time domain. Both the time and frequency analysis methods, however, give little information about the system generating the output. In contrast, the nonlinear dynamic neural analysis method we propose has been found to be a useful method for quantifying the complexity (irregularity) of both physical systems and physiological signals. The respiratory motor output depends on the integrated properties of the neural network. PMID- 17282294 TI - Chaotic dynamics of ventilatory flow in humans. AB - The present study provides further insights into the chaotic nature of the ventilatory behaviour in spontaneously breathing heal thy humans by applying the noise titration method t o ventilatory flow signals gathered in this s e t t i n g . In five subjects with normal breathing pattern and end-tidal CO2, the noise titration method gave a positive noise limit ranged from 6 to 43%. Our study shows that the noise titration technique does find chaos in the ventilatory behaviour o f healthy humans at rest, therefore opening the way to further investigations. PMID- 17282295 TI - Signal Processing and Modelling for the Complex CardiorespiratoryInteractions. PMID- 17282296 TI - Nonlinear interaction of voluntary breathing and cardiovascular regulation. AB - To investigate the effects of voluntary breathing on respiratory sinus arrhythmia and nonlinearity of heart rate variability (HRV), two kinds of voluntary breathing, speech and breath-holding, were used. The results showed that both types of voluntary breathing diminished the high frequency component of HRV, but speech decreased, while breath-holding enhanced the nonlinearity of HRV as detected by the Volterra series method. This finding indicates that respiratory patterns have a variety of influences on cardiovascular regulation. PMID- 17282297 TI - Fibrillation complexity as a predictor of successful defibrillation. AB - A major focus of Implantable Cardioverter Defibrillator (ICD) research has been to reduce the defibrillation shock energy to prolong battery life and provide an enhanced quality of life for the patient. We investigated whether the degree of disorganization (complexity) of the electrogram is correlated with defibrillation shock outcome. The study data sets were recorded using the high voltage leads of an ICD during device implantation. A total 57 data segments from 19 patients were analyzed. Beat cycles were identified using a novel wavelet based method. Two algorithms were proposed and implemented to quantify the disorganization of the electrogram signals: Approximate Entropy and Cross Correlation. Entropy Index based on the ApEn method, was able to discriminate successful episodes from failure ones with a specificity of 93% and sensitivity of 100%. Similarity Index based on Cross correlation method, obtained a specificity of 72% and sensitivity of 66%. We conclude that the organization of a VF episode is related to the minimum energy required for successful defibrillation. PMID- 17282298 TI - Wireless Real-Time Head Movement System Using a Personal Digital Assistant (PDA) for Control of a Power Wheelchair. AB - Loss of mobility can occur for a variety of reasons,such as spinal cord injury or motor neurone disease. The onset of these conditions often brings with it an associated loss of personal independence, which is primarily due to the fact that the sufferer is no longer able to control their mobility. This project aims to address this problem through the creation of a head movement based wheelchair control system. Using a personal digital assistant (PDA) artificial intelligence techniques on an embedded LINUX operating system, a wireless head movement wheelchair control system has been designed and implemented. This system provides relief for sufferers of conditions which inhibit mobility through a method of wheelchair control which offers enhanced ease of use, attractiveness and independence. PMID- 17282299 TI - Noninvasive assessment of cardiovascular autonomic control in pediatric obstructive sleep apnea syndrome. AB - Studies suggest that obstructive sleep apnea syndrome (OSAS) is causally related to abnormal cardiovascular autonomic control in adults, but this has not been established in pediatric OSAS. The goal of this study was to quantify autonomic system dysfunction, as manifested by cardiovascular response abnormalities, in children with OSAS. During wakefulness, we continuously measured the ECG, arterial blood pressure and airflow in each subject. These measurements were made during the following conditions: spontaneous breathing in the supine posture (baseline), spontaneous breathing in the standing posture (orthostatic stress); tracking of the subject's own prior spontaneous breathing pattern while supine (mental stress), and during a cold face challenge. Using spectral analysis and modeling techniques, we sought to computationally delineate the physiological mechanisms that mediate these abnormalities. Our preliminary results suggest that the autonomic effects of pediatric OSAS differ from those in adult in that parasympathetic activity remains relatively normal despite the elevated peripheral sympathetic drive. PMID- 17282300 TI - Adaptive change point detection for respiratory variables. AB - Current alarm strategies for physiological monitoring depend on predetermined thresholds without consideration for the heterogeneity between patients or intraoperative variations. To improve upon this situation, we developed an adaptive change point detection scheme to automatically notify the clinician when a change of clinical significance has occurred in the respiratory variables. We modeled End-Tidal Carbon Dioxide, Expiratory Minute Volume, and Respiratory Rate using a dynamic linear growth model, whose noise covariances are estimated by an adaptive Kalman filter based on a recursive Expectation-Maximization method. Change points are detected by the CUSUM testing. The comparison of the results with post-hoc expert annotations demonstrates that the algorithm can accurately detect relevant changes in the respiratory signals. PMID- 17282301 TI - Computer-assisted arthroplasty using bio-engineered autografts. AB - Recent advances in tissue-engineered cartilage open the door to new clinical treatments of joint lesions. Common to all therapies with in-vitro engineered autografts is the need for optimal fit of the construct, to allow screwless implantation and optimal integration into the live joint. Computer Assisted Surgery techniques are prime candidates to ensure the required accuracy while at the same time simplifying the procedure. A pilot study has been conducted aiming at assembling a new set of methods to support ankle joint arthroplasty using bio engineered autografts. Computer assistance allows planning of the implant shape on a CT image, manufacturing the construct according to the plan and interoperatively navigating the surgical tools for implantation. A rotational symmetric model of the joint surface was used to avoid segmentation of the CT image; a new software was developed to determine the joint axis and make the implant shape parameterisable. A complete cycle of treatment from planning to operation was conducted on a human cadaveric foot, thus proving the feasibility of computer-assisted arthroplasty using bio-engineered autografts. PMID- 17282302 TI - A Wavelet Approach to Detecting Electrocautery Noise in the ECG. AB - A software approach has been developed for detecting electrocautery noise in the electrocardiogram (ECG) using a wavelet decomposition of the signal. With this approach, a clinical monitoring expert system can be forewarned of potential artefacts in trend values derived from the ECG, allowing it to proceed with caution when making decisions based on these trends. In 15 operations spanning 38.5 hours of ECG data, we achieved a false positive rate of 0.71% and a false negative rate of 0.33%. While existing hardware approaches detect the source of the noise without any ability to assess its impact on the measured ECG, our software approach detects only the presence of noise in the signal itself. Furthermore, the software approach is cheaper and easier to implement in a clinical environment than existing hardware approaches. PMID- 17282303 TI - A Viral Envelope as a Vehicle for Tracer, Drug, and Gene Delivery: Initial Biodistribution Study Using PET Imaging. AB - Viral envelopes can be used as an effective vehicle to deliver imaging tracers as well as therapeutic drugs and genes. However, the current methods for in vivo tracking of viral envelopes are limited. This purpose of this study is to investigate dynamically the in vivo biodistribution of viral envelopes using positron emission tomography (PET) imaging. The hemagglutinating virus of Japan envelope (HVJ-E) was labeled with radioactive fluorine (F-18) for tracking with PET imaging. Due to the low molecular weight of F-18, the encapsulation process by HVJ-E was optimized using the cationic agent poly-L-lysine (PLL, MW 66.7 kDa) and Feridex, a magnetic resonance imaging tracer. After labeling, HVJ-Es were injected intravenously into the normal rat and followed for 2 h using high resolution PET imaging. Region of interest analysis showed a significant increase in average liver accumulation based on radioactivity as compared to all control subjects. Average brain uptake showed a significant increase in radioactivity as compared to control subjects receiving F-18-PLL complexes or F-18 alone. Control subjects showed F-18 uptake primarily in the bones. These results demonstrate a molecular imaging technique that can be used to monitor drug and gene delivery and evaluate potential targeting mechanisms. PMID- 17282304 TI - Automated Image Analysis of Fluorescence Microscopic Images to Identify Protein protein Interactions. AB - The identification of protein-protein interactions along with their spatial and temporal localization is vital data for assigning functional information to proteins. Historically, these data sets obtained from fluorescence microscopy, have been analyzed manually, a process that is both time consuming and tedious. The development of an automated system that can measure the location dynamics of the interaction between two proteins inside a live cell is a high priority. This paper describes an automated image analysis system used to identify the interactions between two proteins of interest fused to either GFP or DIV IVA, a bacterial cell division protein that localizes to the cell poles [1]. Upon the induction of DIV IVA fusion protein expression, the GFP-fusion protein will be recruited to the cell poles if a positive interaction occurs. Advanced image processing and feature extraction algorithms are discussed in detail and a statistical feature set used to quantify the image-based information is developed. PMID- 17282305 TI - Tools for Modelling Biological Systems with CellML. AB - The CellML language is an XML-based specification for representing mathematical models of biological processes. The University of Auckland's Bioengineering Institute is committed to creating tools and evolving the language so that biologists and modelers can build, understand, and share models. The CellML standard and tool developments are open source; we encourage researchers and software developers to become involved in the process. The model repository already has a large array of biological models; we expect this to grow rapidly as more researchers adopt the tools and modelling environments we offer which encourages the reuse and sharing of models. PMID- 17282306 TI - A novel method for creating a 2-d parameterized finite element model of the human femur with matching artificial hip joint based on x-ray image. AB - There is a novel method for creating a 2-d parameterized finite element model of the human femur with matching artificial hip joint based on X-ray image before the hip joint replacement surgery. It can help us to evaluate the selected appropriate hip joint prosthesis. PMID- 17282307 TI - Evaluating Estimates of Markov Models of Sequence Evolution through Simulation. AB - Current methods of evaluating techniques that estimate parameters of Markov models of sequence evolution require sequence data from populations with well known phylogenetic relationships. Such data is not always available, since phylogenetic relationships can never be known with certainty. We propose generating sequence data for estimation technique evaluation by simulating sequence evolution in a controlled setting. Our elementary simulator assumes a Markov model and uses a binary branching process to dynamically build a phylogenetic tree from an initial seed sequence. We then observe how well estimation techniques recover the Markov model parameters specified in the simulation using the sequences at the leaves of the tree. We demonstrate our evaluation method on Arvestad and Bruno's estimation technique, and show how our approach can reveal performance variations. PMID- 17282308 TI - Bioinformatic system modeling on hetian uygur natural longevity people. AB - Longevity and life science are active topics in biomedicine and other subjects. In this research, longevity people from Hetian area in Xinjiang, China are used as an example. The cause of longevity is discussed and a bioinformatic longevity model is established based on the medical findings. Human life is a complex multi variant natural process. It is complicated yet important to extract expert knowledge that can describe the interactions among different factors and influence of the factors on human life. Artificial intelligent (AI) and information processing techniques are used to efficiently process large amount of collected biomedical data and effectively extract hidden information into the longevity model. The test results show that the established model is able to identify individuals who belong to longevity group with over 90 percent accuracy. This research creates a new approach to explore the cause of formation of human longevity based on comprehensive medical data rather than just from one medical subject. More importantly, this research explores a practical way to model complex bioinformatic systems. PMID- 17282310 TI - mathematical analysis of the hiv-1 infection : parameter estimation, therapies effectiveness and therapeutical failures. AB - This paper presents a method to estimate accurately the parameters involved in the HIV-1 infection. An application to the evaluation of the drugs effectiveness and therapeutical failures is presented. PMID- 17282309 TI - 3D CT Imaging for Craniofacial Analysis Based on Anatomical Regions. AB - The development of a craniofacial database is a multidisciplinary initiative that will provide an important reference for community, security, social and medical applications. A method of landmark identifications and measurements in 3d on craniofacial patients is described. anatomical regions such as mandible, orbits, zygoma and maxilla are located, created and stored as templates of 3D CAD files for subsequent analysis. Data from these images were tested for accuracy and repeatability by comparing with direct measurements using caliper and CMM. The landmark points are reproducible in CAD system for further analysis. it was found that the approach provides a fast, accurate and efficient method for landmarks identification of the craniofacial areas in database development. PMID- 17282311 TI - A Novel spectral Analysis Method of Atrial Fibrillation Signal Based on Hilbert Huang Transform. AB - Time/frequency analysis has been extensively used in biomedical signal processing. By extracting some essential features from the electro-physiological signals, these methods are able to determine the clinical pathology mechanisms of some diseases. Fourier spectrum analysis provides a common framework for examining the distribution of global energy in the frequency domain. However, this method assumes that the signal should be stationary, which limits its application in non-stationary system. Atrial fibrillation (AF) is a complex nonlinear pathological phenomena, and recently receives a significant amount of research effort. In this work we develop a new signal processing method using Hilbert-huang transform to perform spectral analysis of the atrial fibrillation signals (AFs). This method provides a new analysis tool for AFs. Our experimental results show that it improves the spectral resolution and enables us to understand the episode of AF more precisely. PMID- 17282312 TI - Novel approach for time-varying bispectral analysis of non-stationary EEG signals. AB - novel parametric method, based on the non-Gaussian AR model, is proposed for the partition of on-stationary EEG data into a finite set of third-order stationary segments. With the assumption of piecewise third-order stationarity of the signal, a series of parametric bispectral estimations of the non-stationary EEG data can be performed so as to describe the time-varying non-Gaussian nonlinear characteristics of the observed EEG signals. A practical method based on the fitness of third-order statistics of the signal by using the non-Gaussian AR model, together with an algorithm with CMI is presented. The experimental results with several simulations and clinical EEG signals have also been investigated and discussed. The results show successful performance of the proposed method in estimating the time-varying bispectral structures of the EEG signals. PMID- 17282313 TI - Analyze the dynamic features of rat EEG using wavelet entropy. AB - Wavelet entropy (WE), a new method of complexity measure for non-stationary signals, was used to investigate the dynamic features of rat EEGs under three vigilance states. The EEGs of the freely moving rats were recorded with implanted electrodes and were decomposed into four components of delta, theta, alpha and beta by using multi-resolution wavelet transform. Then, the wavelet entropy curves were calculated as a function of time. The results showed that there were significant differences among the average WEs of EEGs recorded under the vigilance states of waking, slow wave sleep (SWS) and rapid eye movement (REM) sleep. The changes of WE had different relationships with the four power components under different states. Moreover, there was evident rhythm in EEG WEs of SWS sleep for most experimental rats, which indicated a reciprocal relationship between slow waves and sleep spindles in the micro-states of SWS sleep. Therefore, WE can be used not only to distinguish the long-term changes in EEG complexity, but also to reveal the short-term changes in EEG micro-state. PMID- 17282314 TI - Effects of extremely low frequency electromagnetic fields on electrocardiogram: analysis with quadratic time-frequency distributions. AB - Recently we have studied the effects of extremely low frequency pulsed electromagnetic fields (ELF-PEMF) on the human biosignals. Electrocardiogram (ECG) and electroencephalogram (EEG) of seventeen healthy volunteers before and after the electromagnetic (EMF) exposure were recorded and analyzed. The root mean square (RMS) values of the recoded data were considered as comparison criteria. EEG results were shown that there were small variations in the brain electrical activity before and after exposure. The ECG power level was increased up to 1% for most of the subjects. In this paper, we further investigate the effects of the ELF-PEMF on the ECG signal using the hyperbolic T-distributions (HTD). This distribution was shown to be suitable for efficient amplitude and instantaneous frequency (IF) estimation of monoand multicomponent FM signals. In this work, we introduce this distribution to the analysis of ECG signals. The simulation results show that the HTD have a good performance in the analysis of the ECG signals comparing with the Choi-Williams distribution (CWD). Moreover, the results show that there are small shift in the frequency-domain signal before and after EMF exposure. PMID- 17282315 TI - Adaptive Spectrogram for Surface EEnG Analysis. AB - Electroenterogram (EEnG) is the myoelectrical signal of the small bowel. It is the result of a permanent slow wave (low frequency component) and series of spike bursts (high frequency component) that are only present when a bowel contraction occurs. This means spectral content of EEnG changes throughout time. The definition of a t-f distribution that adapts to changes in EEnG spectrum could be very helpful to study this signal. Nine recording sessions of surface EEnG were carried out in three Beagle dogs in fast state. It was proposed an algorithm that selects the window length of spectrogram depending on the maximum frequency of interest of signal in previous window. The proposed adaptive spectrogram was applied to surface EEnG. When only slow waves are present, the adaptive spectrogram enlarges window length in order to present good frequency resolution to characterize the low frequency component of the EEnG. When spike bursts appear, windows of analysis are shorter reducing time resolution to identify individual units of slow waves accompanied by SB. The proposed adaptive spectrogram can be a helpful tool to identify surface EEnG activity in time and frequency domain. It is also likely to be adapted to study other multicomponent signals. PMID- 17282316 TI - Glucosim: educational software for virtual experiments with patients with type 1 diabetes. AB - GLUCOSIM is an educational software package that simulates blood glucose and insulin dynamics in healthy individuals and patients with type 1 diabetes. It is being used to assist biomedical and chemical engineering students in visualizing the dynamic variations in blood glucose concentration in response to external variations such as food consumption and insulin administration. A nutritional database has been integrated to GLUCOSIM to provide meal inputs to the simulation. The simulator has been improved by the modification of mathematical models, and it has been adapted to include currently available commercial insulin brands. PMID- 17282317 TI - Internet Applications for Computational Biology, the CMISS Web Browser Extension and and Use in Education. AB - The Internet is becoming increasingly accessible and new technologies are enabling the delivery of more features to end users. It is therefore increasingly compelling to develop technology to facilitate the delivery of educational content and computational tools via the Internet. Here we report on the Internet enabling of the CMISS package as a Web browser extension, and its use in a custom online teaching application for medical students. PMID- 17282318 TI - Simulation-Based Training In Electrophysiology By iCELL. AB - A simulation-based training resource was developed for electrophysiology. The resource focuses on computational modeling of cellular bioelectric activity and is called the interactive cell modeling tool (http://ssd1.bme.memphis.edu/icell). iCell can be used as a simulation-based teaching and learning tool for electrophysiology. The site consists of JAVA models of various cardiac cells and neurons, and provides simulation data of their bioelectric activities at single cell level. Each JAVA-based model is menu-driven and presents options to change model parameters or conditions, run and view simulation results. iCell has been used as a teaching and learning tool for seven graduate courses at the Joint Biomedical Engineering Program of University of Memphis and University of Tennessee. Scientists from the fields of biosciences, engineering, life sciences and medicine in 17 different countries have also tested and utilized iCell as a simulation-based teaching, learning and collaboration environment. PMID- 17282319 TI - Building Interactive Simulations in Web Pages without Programming. AB - A software system is described for building interactive simulations and other numerical calculations in Web pages. The system is based on a new Java-based software architecture named NumberLinX (NLX) that isolates each function required to build the simulation so that a library of reusable objects could be assembled. The NLX objects are integrated into a commercial Web design program for coding free page construction. The model description is entered through a wizard-like utility program that also functions as a model editor. The complete system permits very rapid construction of interactive simulations without coding. A wide range of applications are possible with the system beyond interactive calculations, including remote data collection and processing and collaboration over a network. PMID- 17282320 TI - Physiological signal processing laboratory for biomedical engineering education. AB - The proposed Physiological Signal Processing Laboratory incorporates important new concepts to further its utility as a vehicle for biomedical engineering educational use. The Laboratory incorporates the physical construction, testing and analysis of eight signal processing circuit modules, introduced as lessons. Each module can be characterized through measurement with a BIOPAC MP35 data acquisition system and a student-built square wave generator. The modules are combined sequentially to create a sophisticated and functional electrocardiogram (ECG) amplification and processing system. By the final lesson, the completed ECG signal processor will provide meaningful outputs from signals sourced from the student's own body. Through the application of a single, easy-to-use data acquisition system and associated software to a breadboard circuitry laboratory, students can build, test and analyze signal processing modules, verify their performance against mathematical simulation using graphical comparisons, combine modules, collect physiological signals sourced from their own bodies, and evaluate the results. By developing the complete ECG signal processor, module by module (as eight lessons), students develop an understanding of system design and development methodologies. In addition, when collecting data directly from their own bodies, students' curiosity is stimulated to create an environment more amenable to inquiry-based learning. PMID- 17282321 TI - Simple analog models to teach electrophysiological concepts. AB - Animal experiments, analog modeling and digital simulations are some means followed in laboratory practices to teach electrophysiological concepts. Advantages and disadvantages of these different strategies may change due to the teaching aims and education levels; none of these ways mentioned above is appropriate alone for all educational purposes. For a beginner who is coming up against the electrophysiological concepts for the first time, experiments on simple analog models would be more educational than all other means. In this work, two analog models involving simple and cheap electrical network components to teach the basic electrophysiological concepts have presented. The first one is suitable to simulate passive membrane properties while the second model involving batteries and manually controllable resistors is suitable to simulate the active membrane properties under space clamped conditions. PMID- 17282322 TI - Improving the Classification of Cirrhotic Liver by using Texture Features. AB - We have been developing a computer-aided diagnosis (CAD) system for distinguishing the cirrhosis in MR images by shape and texture analysis. Two shape features are calculated from a segmented liver region, and seven texture features are quantified by using grey level difference method (GLDM) within the small region-of-interests (ROIs). The degree of cirrhosis is derived from integrating the shape and texture features of the liver into a three-layer feed forward artificial neural network (ANN). A liver is regarded as cirrhosis if the percentage of the ROIs with a degree over 0.5 is greater than 50%. The initial experimental result showed that the ANN can learn all of the patterns in the training data sets. In testing of the whole liver regions, 82% cirrhosis and 100% normal cases were correctly differentiated from 18 test cases, that indicates our proposed method is effective to the cirrhosis prediction on MRI. PMID- 17282323 TI - An Analysis Of Chirpp Data To Predict Severe ATV Injuries Using Artificial Neural Networks. AB - This paper describes the development of a tool to predict the severity of all terrain vehicle (ATV) injuries using artificial neural networks (ANNs). The data was obtained from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP). The main objective of the study was to identify the contribution of input variables in predicting severe injury or death. An ANN architecture with 9 hidden nodes and one hidden layer resulted in optimal performance: a logarithmic sensitivity index of 0.099, sensitivity of 47.3%, specificity of 80.8%, correct classification rate (CCR) of 68.6% and receiver operating curve (ROC) area of 0.711. The minimum data set that can help predict injury severity is discussed. PMID- 17282324 TI - A Real-Time Continuous Cardiac Arrhythmias Detection System: RECAD. AB - Cardiac arrhythmia is a class of serious heart diseases that threatens many people. Current arrhythmias diagnostic techniques seem to be partially efficient due to the application limitations either in time or in space. The paper presents a real-time continuous arrhythmias detection system (RECAD) platform based on the wireless sensor network technology. This system provides long-term real-time surveillance thanks to the low-resource and low power consumptions of ambulatory wireless ECG sensor (AWES). Moreover, the AWES is compact and friendly use, so it enables patients to lead a normal life every where (indoors or outdoors). RECAD platform contains four sub-systems: AWES, local access server, remote access server and remote surveillance server. Each subsystem is configurable to run in multiple operation modes according to different application scenarios. A lossless signal compression algorithm is adopted to reduce network traffics and a dedicated application layer protocol is provided to guarantee a real-time reliable on-line ECG analysis. This system is evaluated on about twenty patients at the hospital Gabriel Montpied of Clermont-Ferrand and the real-time results are similar to the HP telemetry system. PMID- 17282325 TI - Automated Individual Prescription of Exercise with an XML-based Expert System. AB - Continuously motivating people to exercise regularly is more important than finding a barriers such as lack of time, cost of equipment or gym membership, lack of nearby facilities and poor weather or night-time lighting. Our proposed system presents practicable methods of motivation through a web-based exercise prescription service. Users are instructed to exercise according to their physical ability by means of an automated individual prescription of exercise checked and approved by a personal trainer or exercise specialist after being tested with the HIMS, fitness assessment system. Furthermore, utilizing BIOFIT exercise prescriptions scheduled by an expert system can help users exercise systematically. Automated individual prescriptions are built in XML based documents because the data needs to be flexible, expansible and convertible structures to process diverse exercise templates. Web-based exercise prescription service makes users stay interested in exercise even if they live in many different environments. PMID- 17282326 TI - Hybrid data mining ensemble for predicting osteoporosis risk. AB - This paper presents the research in developing data mining ensembles for predicting the risk of osteoporosis prevalence in women. Osteoporosis is a bone disease that commonly occurs among postmenopausal women and no effective treatments are available at the moment, except prevention, which requires early diagnosis. However, early detection of the disease is very difficult. This research aims to devise an intelligent diagnosis support system by using data mining ensemble technology to assist General Practitioners assessing patient's risk at developing osteoporosis. The paper describes the methods for constructing effective ensembles through measuring diversity between individual predictors. Hybrid ensembles are implemented by neural networks and decision tress. The ensembles built for predicting osteoporosis are evaluated by the real-world data and the results indicate that the hybrid ensembles have relatively high-level of diversity and thus are able to improve prediction accuracy. PMID- 17282327 TI - A semi-automatic orthopedic implant management tool for Computer Assisted planning, navigation and simulation: from XML implant database to unified implant access interface. AB - Nowadays, Computer Assisted Orthopedic planning and navigation systems have been recognized as an important tool that helps surgeons. Various systems have been developed so far, but most of them use non-standard formalisms and techniques. As a result there are no standard concepts for implant and tool management or data formats to store information for use in 3D planning and navigation systems. We addressed these limitations and developed a practical and generic solution which brings benefits for surgeons, implant manufacturers and CAS application developers. We developed a virtual implant database containing geometrical as well as calibration information for orthopedic implants and instruments with a focus on Trauma. This database has been successfully tested with various applications in client/server mode. Nevertheless, the implant information is not static because periodically manufacturers revise implants, resulting in the removal of some implants and addition of new ones. To ease the implant management in respect to implant life cycle, we developed an implant management tool which helps end-users to manage their implants. Currently, this tool allows the addition of new implants, modification of existing ones, deletion of obsolete implants, export of a given implant and also creation of backups. Our implant management system has been successfully tested in the laboratory and gave very promising results. It makes it possible to fill the current existing gap between CAS system, implant manufacturers, hospitals and surgeons. PMID- 17282328 TI - Gene Expression Data for DLBCL Cancer Survival Prediction with A Combination of Machine Learning Technologies. AB - Gene expression profiles have become an important and promising way for cancer prognosis and treatment. In addition to their application in cancer class prediction and discovery, gene expression data can be used for the prediction of patient survival. Here, we use particle swarm optimization (PSO) to address one of the major challenges in gene expression data analysis, the curse of dimensionality, in order to discriminate high risk patients from low risk patients. A discrete binary version of PSO is used for gene selection and dimensionality reduction, and a probabilistic neural network (PNN) is implemented as the classifier. The experimental results on the diffuse large B-cell lymphoma data set demonstrate the effectiveness of PSO/PNN system in survival prediction. PMID- 17282329 TI - An Automatic and Power Spectra-based Rotate Correcting Algorithm for Microarray Image. AB - Microarray image analysis, an important aspect of microarray technology, faces vast amount of data processing. At present, the speed of microarray image analysis is quite limited by excessive manual intervention. The geometric structure of microarray determines that, while being analyzed, microarray image should be collimated in the scanning vertical orientation. If rotation or tilt happens in microarray image, the analysis result may be incorrect. Although some automatic image analysis algorithms are used for microarray, still few methods are reported to calibrate the microarray image rotation problem. In this paper, an automatic rotate correcting algorithm is presented which aims at the deflective problem of microarray image. This method is based on image power spectra. Examined by hundreds of samples of clinical data, the algorithm is proved to achieve high precision. As a result, adopting this algorithm, the overall procedure automation in microarray image analysis can be realized. PMID- 17282330 TI - Improved probe selection for DNA arrays using nonparametric kernel density estimation. AB - Oligonucleotide fingerprinting of rRNA genes (OFRG) is a method for identifying arrayed ribosomal RNA genes (rDNA) through a series of hybridization experiments with short oligonucleotide probes. Due to its low cost and high speed, it is an effective tool for analyzing microbial communities. OFRG relies on probe sets that can discriminate large collections of clones. Although the currently used probe design algorithm produces probe sets whose theoretical accuracy is close to optimum, those probes often do not hybridize in a consistent and predictable manner in actual biological experiments. We assume that these failures occur following an unknown probability distribution. In this paper, a nonparametric kernel density estimation method is proposed to estimate this distribution and to predict probe reliability. These predictions are used to reduce the number of unreliable probes chosen by the probe design algorithms. Our preliminary results show that the application of this method leads to a significant decrease in the number of unreliable probes. PMID- 17282331 TI - Finding co-clusters of genes and clinical parameters. AB - For better understanding of genetic mechanisms underlying clinical observations, we often want to determine which genes and clinical traits are interrelated. We introduce a computational method that can find co-clusters or groups of genes and clinical parameters that are believed to be closely related to each other based upon given empirical information. The proposed method was tested with data from an Acute Myelogenous Leukemia (AML) study and identified statistically significant co-clusters of genes and clinical traits. The validation of our results with Gene Ontology (GO) as well as the literature suggest that the proposed method can provide biologically meaningful co-clusters of genes and traits. PMID- 17282332 TI - The response of the metabolic network of the red blood cell to pyruvate kinase deficiency. AB - The response of the metabolic network of human red blood cell is investigated using the E-Cell simulation system when pyruvate kinase (PK) is deficient. The results that several downstream metabolites of the glycolysis pathway accumulate are in a good agreement with experimental data reported in literatures. This accumulation results in the reaction that phosphoglycerate kinase (PGK) catalyzes reversing its direction. Mathematical analysis to the simulation results shows that the PGK-catalyzing reaction reversing its direction happens simultaneously with an abrupt change of the second derivative of the ATP quantity. PMID- 17282333 TI - Effect of outlier removal on gene marker selection using support vector machines. AB - Biological markers are useful tools for the diagnosis and prognosis of disease. Many different methods are currently used to extract markers from multiple data sources, including gene expression microarrays. This paper investigates the effect of outlier removal on the performance of one such biomarker selection method, Support Vector Machines (SVM). A simple method of outlier removal is employed as a preprocessing step before the data is used for SVM analysis. Both linear and radial basis kernels are used as well as four different normalization techniques. Results show that outlier removal increases the number of highly predictive genes as well as the number of poorly predicting genes. This result thus supports the use of outlier removal prior to biological marker identification via SVM analysis. PMID- 17282335 TI - Insignificant effects of plasma catecholamines on dynamic heart rate regulation by the cardiac sympathetic nerve. AB - Although plasma catecholamines such as norepinephrine (NE) and epinephrine (Epi) increase during severe exercise, the effects of high levels of plasma catecholamines on dynamic heart rate (HR) regulation by the cardiac sympathetic nerve remains unknown. The aim of the present study was to examine the effects of plasma catecholamines on the transfer function from sympathetic nerve stimulation to HR. In anesthetized rabbits, we randomly stimulated the right cardiac sympathetic nerve according to a binary white noise signal while measuring HR. The effects of intravenous NE administration at 1 and 10 mugmiddotkg 1middoth-1 were examined in 6 rabbits. The effects of intravenous Epi administration at 1 and 10 mugmiddotkg-1middoth 1 were examined in different 6 rabbits. Although plasma NE increased 10 times as high as the baseline level during the NE administration at mugmiddotkg-1middoth-1 , dynamic gain of the transfer function was not changed significantly (7.1plusmn1.2, 6.9plusmn1.1, and 7.7plusmn1.1 beatsmiddotmin-1middotHz-1). Similarly, although plasma Epi increased 10 times as high as the baseline level during the Epi administration at 10 mugmiddotkg-1middoth-1, dynamic gain of the transfer function was not changed significantly (7.5plusmn0.8, 7.9plusmn0.8, and 7.6plusmn1.2 beatsmiddotmin-1middotHz-1). In conclusion, plasma catecholamines of physiologically-relevant high concentrations did not interfere with the dynamic HR regulation by the cardiac sympathetic nerve. PMID- 17282334 TI - Selective quantification of cardiac sympathetic and parasympathetic nervous function from non-invasive measurements. AB - Power spectral analysis of spontaneous heart rate (HR) variability is a popular and convenient technique for quantifying cardiac autonomic nervous function. While this technique can provide an effective index of parasympathetic nervous function, it cannot provide a pure index of A -sympathetic nervous function. We have developed a non-invasive technique for selectively quantifying cardiac sympathetic and parasympathetic nervous function by employing a multi-signal approach in conjunction with prior physiologic knowledge. We have tested the technique in 14 human subjects under pharmacological autonomic blockade, and our results show that the technique can substantially outperform traditional HR power spectral indices in terms of predicting the known drug effects. PMID- 17282336 TI - Carvedilol Protects Early Diabetic Rat Hearts through Reducing Oxidative Stress. AB - The risk for cardiovascular disease is significantly high in diabetes mellitus. Experimental evidence suggests that oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Carvedilol, a non-selective beta-adrenoceptor and selective alpha1-adrenoceptor blocker, also has antioxidant and free radical scavenger properties. In the present study the effect of carvedilol on the antioxidative status of cardiac tissue was investigated in streptozotocin (STZ) induced early diabetic rats. The subjects were randomly divided into age-matched rats, STZ-induced untreated diabetic rats, small and large dosage (1mg/kg/d or 10mg/kg/d) carvedilol-administrated diabetic rats. After 5 weeks, hemodynamic parameters, echocardiography characteristics and the levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) in the cardiac tissues of all groups were meassured. Diabetic rats had lower ejection fraction, fractional shortening, and higher systolic pressure, diastolic pressure and developed pressure. These parameters were improved by administration of carvedilol. Diabetic rats showed elevated MDA level and CAT activity, but lower activities of SOD and GSH-Px. Carvedilol treatment increased activities of SOD and GSH-Px in diabetic rats. These results indicate that carvedilol improves cardiac function via its antioxidant property in diabetic rats. PMID- 17282337 TI - Modelling cardiac dynamics with integral pulse frequency modulated units. AB - We investigate a new model for the cardiac system. It embodies the main features of cardiac activity with great flexibility. It can be tuned to suit different cell types, and scaled up or down to represent either a single cell, an aggregate, or whole tissue. We demonstrate its use in the generation of a clinically realistic electrocardiogram (ECG) and other dynamical behaviours such as spiral waves. Our model is computationally economic - about 1000 times faster than ion conductance based models and is thus ideal for doing large scale simulations. PMID- 17282338 TI - An Efficient Algorithm to Reconstruct Heart Rate Signal Based on an IPFM Model for the Spectral Analysis of HRV. AB - This paper introduces an efficient algorithm to reconstruct heart rate signal based on an integral pulse frequency modulation (IPFM) model. The heart rate signal was reconstructed by the summation of a set of sinc functions with different weights, whose value could be determined from the IPFM process. Simulation study demonstrated that the signal reconstructed by the proposed method would preserve high frequency component with less distortion than the popular derivative of cubic spline interpolation (DCSI) method. When applied to the spectral analysis of heart rate variability (HRV) of simulated heart rate signal, the proposed method achieved smaller bias than the DCSI method. Therefore, the proposed method would be beneficial for the reconstruction of heart rate signal and the relevant spectral analysis of HRV in the future. PMID- 17282339 TI - Multiple Factor Analysis of the Autonomous Nervous System during PTCA. AB - This study describes the Autonomic Nervous System (ANS) response before, during and after a percutaneous transluminal coronary angioplasty (PTCA). The study population consisted of 37 patients undergoing PTCA from Staff-3 Database. Classical Heart rate variability (HRV) parameters: RR mean, SD, rMSSD, LF, HF, LF/HF and LF/(HF+LF) were extracted and a multiple factorial analysis (MFA) was carried out. Preliminary results show that sympathetic activity increases during and after PTCA, and global HRV decreases during PTCA and increases after PTCA. These findings suggest that MFA provides a powerful tool allowing assessment of ANS's response during PTCA. PMID- 17282340 TI - A new muscle artifact removal technique to improve the interpretation of the ictal scalp electroencephalogram. AB - In this paper a new method for muscle artifact removal in EEG is presented, based on Canonical Correlation Analysis (CCA) as a Blind Source Separation technique (BSS). This method is demonstrated on a synthetic data set. The method out performed a low pass filter with different cutoff frequencies and an Independent Component Analysis (ICA) based technique for muscle artifact removal. The first preliminary results of a clinical study on 26 ictal EEGs of patients with refractory epilepsy illustrated that the removal of muscle artifact results in a better interpretation of the ictal EEG, leading to an earlier detection of the seizure onset and a better localization of the seizures onset zone. These findings make the current method indispensable for every Epilepsy Monitoring Unit. PMID- 17282341 TI - Rule-enhanced Clustering in the Detection of Neonatal Seizures. AB - This paper describes a three-stage system for the detection of neonatal seizures. The first stage detects 5-s seizure segments using signal processing and pattern recognition techniques. In the second stage, the seizure segments overlapping with artifactual segments are marked for post-processing using rules. Rules add intelligence to the spatio-temporal clustering in the third stage, by incorporating knowledge of known seizure characteristics, spatial context, and occurrence of artifacts, in order to reduce false detections. The false detection rate has been reduced without significantly lowering the sensitivity of the seizure detection process. In 21 subjects (11 with seizures and 10 without seizures), the false detection rate was less than 1/hr while sensitivity of seizure detection was 85%. The focus of this paper is the second and third stages of the system. PMID- 17282342 TI - Intracranial Electrode Visualization in Invasive Pre-surgical Evaluation for Epilepsy. AB - Invasive intracranial electroencephalography (EEG) studies help identify the epileptogenic focus and assess if the identified zone overlies eloquent cortex by means of cortical stimulation. Proper interpretation and use of the intracranial recording/stimulation studies requires an effective display of multimodal information. We developed a software system which can combine the patient's segmented brain, post-implanting MRI/CT images, intracranial EEG findings and results from cortical stimulations into one integrated environment of three dimensional visualization. This platform can efficiently facilitate the epilepsy pre-surgical evaluation and epilepsy surgery planning. PMID- 17282343 TI - On the use of Spectrally Constrained ICA applied to single-channel Ictal EEG recordings within a Dynamical Embedding Framework. AB - Within a dynamical embedding (DE) framework it is possible to extract information on multiple-sources underlying just a single channel recording of electromagnetic brain activity. Independent Component Analysis (ICA) is a technique which, when used in conjunction with DE, can identify and extract statistically independent sources underlying these single channel recordings. However, these powerful techniques still generally require subjective a posteriori analysis in order to visualise neurophysiologically meaningful components in the outputs. For this reason we introduce a variant of ICA known as constrained ICA (cICA) which allows for the extraction of one of many sources underlying the measurement signal, through the provision of a basic reference signal. This constraint can be chosen to reflect neurophysiological prior knowledge of the sources in question given the measured signal. Here we present a technique which allows for the application of spectral constraints on single channel recordings of epileptic EEG data. We show that through a combination of DE and cICA it is possible to extract meaningful information on epileptic seizures and other rhythmic activity from just a single channel of EEG. We further show that accurate extraction of the sources of interest is not critically dependent on the closeness of the measurement channel to the location of the source activity. PMID- 17282344 TI - Effectiveness of daily short-duration standing in preventing post-suspension cardiovascular dysfunction in rats assessed by cardiovascular signal analysis. AB - The aim of the present study was to clarify whether simulated microgravity induced post-suspension cardiovascular deconditioning in rats could be prevented by daily short-duration standing (STD). Three groups of rats were used as subjects to perform the experiments. Compared to a control group of male Sprague Dawley rats (CON), a group of rats with tail-suspension (SUS) for 28 d was used to simulate cardiovascular deconditioning due to microgravity. Another group of tailed-suspended rats with daily STD for 1 h was used to provide -GX (dorso ventral) gravitational loading as countermeasure. In addition to hemodynamic changes to head-up tilt, blood pressure variability (BPV) signals were also analyzed by spectral and nonlinear analysis. The results showed 1) Blood pressure immediately decreased after head-up tilt in all three groups. After several minutes, blood pressure could restore to the initial condition in both CON and SUS+STD group, but the recovery process was slower in the latter group. In contrast, the recovery process was the slowest in the SUS group and could not restore to the initial level completely. 2) In frequency domain, power spectra has similar pattern in CON and SUS+STD group. However, they are quite different in the SUS group in that spectra peak is obvious increased in very low frequency and spectra is narrower and higher in high frequency. PMID- 17282345 TI - Protection of force incentive on bone lose of tail-suspended rats. AB - It has been documented that astronauts suffer from a progressive and continuous negative calcium balance in space flight. The aim of this trial was to demonstrate the role of force incentive on protection of bone lose in stimulated microgravity rats. MATERIALS AND METHODS: 7-week-old male Wistar rats were randomly divided into 3 groups. One group was suspended by tail for 21 days, one groups were suspended for 21 days and play 1 minutes/day of force incentive (2N, 10 Hz), one group served as control. bone mass, biomechanical properties, histomorphometry and biochemical marked were determined. Results Short-time force incentive not only can improve the metabolism of calcium and phosphorus as well as histomorphometry of tibia, but also can increase bone mineral, biomechanical properties and decrease the content of NO in femur. Conclusion Short-time force incentive can protect the bone lose in stimulated microgravity. Compare with the traditional methods such as using drug, the physical methods, for example, short time force incentive are less vehement and more safety, which can maintain the normal structure of bone. So short-time force incentive maybe can develop to the primary protective method on osteoporosis. PMID- 17282347 TI - A preliminary biophysical report on the fertilized eggs traveled with spaceflight. PMID- 17282346 TI - The role of ERK in phasic and tonic contractile responses in rat femoral arteries after hindlimb unloading. AB - The present study tested the hypothesis that the role of ERK in phasic and tonic contractile responses is declined by hindlimb unloading (HU) in rat femoral arteries. Male Wistar rats were randomised into HU and Control group (n=7). After 14d, the femoral arteries were isolated and cut into 3-mm ring segments. In the absence or presence of PD98059(MEK inhibitor), contractile response to NE(10μM) was measured in Krebs solution in a tissue bath at 37°C, isometric tension were recorded with Powerlab system. The area under curve (AUC), phasic and tonic contractile responses between two groups were compared. After 14d-HU, the AUC, phasic and tonic NE-induced contractile responses were declined compared with controls. PD98059 did not affect the AUC in arteries from HU, but significantly decreased the AUC in arteries from control (100±7.1% vs. 61.18±11.3%, P<0.05). In contrast to control, the inhibitory ratio of PD98059 was significantly lower in phasic (7.42±3.24% vs. 33.59± 9.19%, P=0.0198) and tonic (26.93±3.78% vs. 46.75±5.67%, P=0.0131) contractile responses of HU group. Moreover, the inhibitory ratio of PD98059 wasn't significantly different between the phasic and tonic contractile responses in control group (P=0.2464). But for HU group, the difference was statistically significant (P=0.002). We demonstrated that the role of ERK was declined in both phasic and tonic contractile responses in rat femoral arteries after hindlimb unloading. Simulated microgravity induced by HU may attenuate the contractile responses of femoral arteries by inhibiting the role of ERK in thick and thin filament regulatory pathways. PMID- 17282348 TI - Elastographic Imaging of the Strain Distribution at the Anterior Cruciate Ligament and ACL-Bone Insertions. AB - The anterior cruciate ligament (ACL) functions as a mechanical stabilizer in the tibiofemoral joint. Over 250,000 Americans each year suffer ACL ruptures and tears, making the ACL the most commonly injured knee ligament. Methods which permit the in situ monitoring of changes in ACL graft mechanical properties during healing are needed. A long term goal in ACL reconstruction is to regenerate the ACL-bone interface. To this end, an understanding of mechanical properties of the ligament-bone interface is needed. However, experimental determination has been difficult due the small length scale (<1 mm) involved and limited resolution of standard techniques. The current study uses elastography to characterize the functional properties of the ACL and the ACL-bone interface under applied load. In a first experiment, bovine joints were excised, cast in an agar gel matrix and externally compressed. In a second experiment, tibiofemoral joints were mounted on a MTS 858 Bionix Testing System. The ACL was loaded at different strain rates and tested to failure while RF data was collected at 5 MHz. For both tensile and compression testing, axial elastograms between successive RF frames were generated using cross-correlation and recorrelation techniques. When the ACL-bone complex was tested in the tibial alignment on the MTS system, compressive strains were found to dominate at the tibial insertion. Compressive strains were observed in the ligament proper when the transducer beam was aligned with respect to the insertion during loading. PMID- 17282349 TI - Fast reconstruction of tissue elastic modulus image by ultrasound. AB - Most technologies for tissue elasticity imaging are now based on measurement of stain distribution, since they are more suited to real-time processing than reconstruction of elastic modulus images. However, to obtain more quantitative information about tissue elastic properties, it is necessary to reconstruct tissue elastic modulus images. There, we developed a new method for reconstructing tissue elastic modulus images at high speed and with high precision based on a modified 3-D finite-element model. In this paper, we verify the validity of the method based on a modified 3-D finite-element model, using simulations and phantom experiments. PMID- 17282350 TI - Reconstruction of Shear Modulus Distribution Together with Poisson's Ratio Distribution and Density Distribution. AB - As a differential diagnosis technique of living soft tissues, we are developing ultrasonic strain measurement-based shear modulus reconstruction methods. Previously, we reported a method utilizing the typical value of Poisson's ratio. However, as reconstruction errors were confirmed due to the difference between the original value and the set value, we proposed a method to reconstruct Poisson's ratio as well. Furthermore, we proposed to reconstruct density as well to deal with dynamic deformation. In this report, to stabilize reconstruction, we propose to use mean normal stress as unknown. The effectiveness is verified through simulations. PMID- 17282351 TI - A theoretical performance assessment tool for myocardial elastography. AB - The main purpose of this paper is to develop a theoretical tool in order to fundamentally characterize the performance of Myocardial Elastography and identify the optimal parameters to be used for the more reliable detection of ischemia or infarction. A complete representation of the left-ventricular function throughout an entire cardiac cycle was previously demonstrated through the use of a 3D finite-element analysis (FEA) model. This FEA model together with an ultrasound image formation model is used here in order to test the performance of 2D Myocardial Elastography at distinct phases of the cardiac cycle and at different states of myocardium, i.e., normal and ischemic, based on in vivo canine data. A previously developed 3D finite-element analysis (FEA) model of a normal canine left ventricle with 80 nodes and 40 elements was used to simulate all main phases of the cardiac cycle. The axial and lateral displacements within multiple image (x-y) planes across the left-ventricular volume were iteratively calculated and corrected to reduce the decorrelation noise. Given the excellent agreement between the FEA solution and the elastographic strains measured in 2D over an entire simulated cardiac cycle, Myocardial Elastography proves to be a reliable technique for the accurate assessment of the myocardial deformation in 2D at distinct phases of the cardiac cycle as well as detection of the ischemic region. Preliminary in vivo results of a standard short-axis view in a canine myocardium are shown validating the performance assessment using the proposed model. PMID- 17282352 TI - Development of a Synchronized System for Continuous Acquisition and Analysis of Ultrasound Joint Angle, and EMG. AB - Ultrasound and electromyography (EMG) are two of the most often used diagnostic tools for muscles. However, there is lack of a system for continuously capturing both signals with a synchronized procedure. This study presents a new system for this purpose. The system comprises an ultrasound scanner, a pulser/receiver, an EMG amplifier, and a PC with A/D converter cards for data acquisition and analysis. The A-mode and B-mode ultrasound data, which were digitized by the A/D converter and a video capture card respectively, could be simultaneously captured by the PC together with the surface EMG (SEMG) signal, which was digitized by another data acquisition card. Time markers for all frames of ultrasound and SEMG signals were recorded to synchronize the two data streams. The tissue deformation was extracted inform the ultrasound signals or images using cross-correlation algorithms. The RMS and spectrum of SEMG was calculated to study the muscle activity. In addition, the joint angle signal was also be synchronized with ultrasound and SEMG signals. The experiments involving 5 subjects were carried out to test the performance of the system. Preliminary results showed that the muscle deformations extracted from the ultrasound data were well correlated with the changes of SEMG RMS. The system may have potential values in the investigation of muscle properties and activities. PMID- 17282353 TI - A novel method to obtain modulus image of soft tissues using water jet compression. AB - Tissue stiffness is generally known to be associated with pathologic changes. Ultrasound indentation is able to assess the mechanical properties of soft tissues. Conventional ultrasound indentation devices use rigid flat-ended transducers to directly contact with the tissues and typically operate in the frequency ranging between 2 M Hz and 10 MHz. This paper introduced a novel ultrasound indentation system using water jet compression. The water jet served as an indenter as well as a medium for the propagation of the ultrasound beam. High frequency focused transducer was used to measure the indentation deformation at a microscopic level. It has been demonstrated that the system could effectively assess the tissue-mimicking phantoms with different stiffness. Moreover, another advantage of this novel indentation system was to apply C-scan on soft tissues rapidly and conveniently. By applying different pressures on C scan sequences, the modulus image of the tissue could be obtained. This paper presented the preliminary results on gel phantoms. The spatial resolution and the sensitivity of the measurements, the reproducibility of the results were also discussed. PMID- 17282354 TI - A correlation study on the variabilities in pulse transit time, blood pressure, and heart rate recorded simultaneously from healthy subjects. AB - This paper proposes to use the pulse transit time variability (PTTV) as an indicator of the variability in hemodynamics and studies its correlation with other cardiovascular variabilities, especially the blood pressure variability (BPV), which receives increasing attentions as an independent indicator of autonomic regulation and abnormalities in cardiovascular system. Continuous blood pressure (BP), electrocardiogram (ECG), and photoplethysmographic (PPG) signal were collected simultaneously from 11 healthy subjects in resting state. Two types of pulse transit time (PTT), defined by different characteristic points of ECG and PPG signals, were measured beat by beat noninvasively. Correlation coefficient was employed to quantify the relationship between the beat-to-beat variabilities in any pair of the target cardiovascular parameters. Significant correlations were consistently observed among the variabilities in systolic BP, pulse BP and PTTf, which was defined as the time interval between the peak of ECG R-wave and the frontal foot of the PPG pulse within the same cardiac cycle. The results of this study indicate that variability in PTTfis highly associated with that in BP and can be potentially used for BPV estimation for healthy subjects at static body state. PMID- 17282356 TI - Development of a wearable device capable of monitoring human activity for use in rehabilitation and certification of eligibility for long-term care. AB - The importance of human posture monitoring is well recognized in the field of rehabilitation, in order to evaluate quantitatively the effectiveness of rehabilitation by a physical therapist. The activity monitoring is also well recognized as being useful in the field of certification of eligibility for long term care. Assessment of the actual physical condition of the applicant tends to be difficult when determine the level of need for long-term care. Taking these circumstances in consideration, we attempted to measure the activities of patients in rehabilitation using a wearable device for monitoring human activity. The results clearly demonstrated that detailed motion characteristics could be detected during standing up, walking and sitting up as angle changes between specific body segments and as trunk motion acceleration. PMID- 17282355 TI - Development of a wearable measurement and control unit for personal customizing machine-supported exercise. AB - Wearable technology has been used in various health-related fields to develop advanced monitoring solutions. However, the monitoring function alone cannot meet all the requirements of personal customizing machine-supported exercise that have biosignal-based controls. In this paper, we propose a new wearable unit design equipped with measurement and control functions to support the personal customization process. The wearable unit can measure the heart rate and electromyogram signals during exercise and output workload control commands to the exercise machines. We then applied a prototype of the wearable unit to an Internet-based cycle ergometer system. The wearable unit was examined using twelve young people to check its feasibility. The results verified that the unit could successfully adapt to the control of the workload and was effective for continuously supporting gradual changes in physical activities. PMID- 17282357 TI - A smart orthosis for the treatment of scoliosis. AB - The tightness of an orthosis for the treatment of scoliosis varies greatly during daily activities. To be effective the orthosis should be maintained at the prescribed tightness to optimize the active component of objective treatment. Subjective feeling is the most commonly used method to evaluate how patients tighten their orthoses. To provide an objective measure, a battery-powered microcomputer system was developed to monitor loads exerted by orthoses during daily living. The system not only records how well the orthosis has been used, but also helps patients wear the orthoses as prescribed. Four subjects have used the system for one month. The proportion of the time that the subject wore the orthosis at the prescribed level increased from 53±10% to 69±16%. The effectiveness of the smart orthosis is still under evaluation. PMID- 17282358 TI - Wearable kinesthetic systems for capturing and classifying body posture and gesture. AB - Monitoring body kinematics has fundamental relevance in several biological and technical disciplines. In particular the possibility to know the posture exactly may furnish a main aid in rehabilitation topics. This paper deals with the design, the development and the realization of sensing garments, from the characterization of innovative comfortable and spreadable sensors to the methodologies employed to gather information on posture and movement. In the present work an upper limb kinesthetic garment (ULKG), which allows to reconstruct shoulder, elbow and wrist movements and a kinesthetic glove able to detect posture an gesture of the hand are presented. Sensors are directly integrated in Lycra fabrics by using conductive elastomer (CE) sensors. CE sensors show piezoresistive properties when a deformation is applied and they can be integrated onto fabric or other flexible substrate to be employed as strain sensors. PMID- 17282359 TI - Wireless Hearing Aid System Simulations using Advanced Design System™: A Behavioral Modeling Approach. AB - The stringent requirements on size and power consumption constrain the conventional hearing aid devices from providing the patients an economic and user friendly solution, specifically for better noise cancellation. With the advancements in technologies such as integrated circuits design, wireless communications and digital signal processing techniques, the wireless hearing aids having multi-microphones, analog, digital and mixed signals and radio frequency signals processing circuits, DSP and programmable units seem to be promising to provide enhanced performance. The focus of this paper is about the system simulation of a typical wireless hearing aid using Agilent Advanced Design System™. The behavioral modeling features are exploited to enable the whole system simulations including electro-acoustic transducers. A few system level simulation results are included. PMID- 17282360 TI - Experimental Study of Two-frequency Dielectrophoresis Effects on a Linear Electrode Array. AB - Dielectrophoresis is a powerful tool for the manipulation of particles and biological cells. The magnitude and direction of the DEP force is determined by the comparative conductivity and permeability of the medium and the particle. Most previous work has focused on single frequency studies. In this paper, we present the work of two frequency dielectrophroesis effects on a linear electrode array. We show results where the advantage of applying two frequencies is to separate particles having similar dielectric properties. In addition, we report the first experimental data on breaking of DEP trapping zone by adding a low frequency signal to the main frequency signal. The phenomenon is due to a system disturbance by electro-hydrodynamic effect and has potential applications in DEP mixing and advanced control of particles. PMID- 17282361 TI - A micro device for separation of erythrocytes and leukocytes in human blood. AB - We report a MEMS device for continuous and binary separation of leukocytes (white blood cells, WBCs) and erythrocytes (red blood cells, RBCs) by their sizes. The system consists of PDMS cylindrical pillars inside fluidic chamber on glass slides. A 420 μm lateral separation was achieved for 5 μm and 10 μm beads. The critical particle size for separation was successful predicted by simulation and experimentally determined by calibration with polystyrene beads. The separation function (lateral displacement versus particle size) was also measured experimentally. Diluted whole blood and blood fraction of concentrated leukocytes were tested with the devices with erythrocyte to leukocyte ratio in agreement with blood count results. Experiments with fluorescent labeled leukocytes confirm the separation of leukocytes from erythrocytes and measured the separation efficiency. PMID- 17282362 TI - Integrated flexible ocular coil for power and data transfer in retinal prostheses. AB - A microfabricated and fully-implantable coil for use as a power and data transfer component for retinal prostheses is presented. Compared with traditional hand made ocular coils, this parylene-based device is thin and flexible with 10 turns of thin-film metal wires and a thickness of less than 10 μm. In addition, the entire coil structure can be heat-formed on a mold to match the eye's curvature for extraocular implantation. Because it is made using parylene thin film technology, this coil can be directly integrated with multielectrode arrays and with parylene-based packages incorporating application specific integrated circuits (ASICs) or discrete electrical components such as chip capacitors. This coil thus enables the fabrication and implantation of a fully microfabricated system for retinal prostheses. PMID- 17282363 TI - High Quality Performance of High-throughput GeneChip® Probe Array System. AB - A high-throughput GeneChip® probe array platform was established. This system offers automated processing of 96 samples in the industry standard 96-well plate format. We demonstrate that this new technology can deliver the same performance as the standard cartridge probe arrays. PMID- 17282364 TI - NTA-Functionalized Poly(L-lysine)-g-Poly(Ethylene Glycol): A Polymeric Interface for Binding and Studying 6 His-tagged Proteins. AB - In this paper, a novel graft copolymer, poly-(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) with part of the PEG chains carrying a terminal nitrilotriacetic acid group (NTA) was synthesized. Through electrostatic interactions, these polycationic graft co-polymers assemble spontaneously from aqueous solution onto negatively charged surfaces, forming polymeric monolayers that present NTA groups at controlled surface densities on a highly PEGylated background. The NTA-functionalized PLL-g-PEG surfaces proved to be highly resistant to nonspecific adsorption in contact with human serum while allowing the specific and reversible surface binding of GFPuv-6His and β-lactamase 6His in native conformation. Micropatterns consisting of NTA-functionalized PLL-g PEG in a background of PLL-g-PEG were produced using the "molecular assembly patterning by lift-off" technique. Exposure to Ni2+and GFPuv-6His resulted in a protein pattern of excellent contrast as judged by fluorescence microscopy. Furthermore, optical waveguide lightmode spectroscopy (OWLS) and a miniature fiber optic absorbance spectrometer (FOAS) were combined as affinity and catalytic biosensor to monitor in situ and quantitatively the amount of immobilized β-lactamase-6His and to determine the activity of the immobilized enzyme. The NTA-functionalized PLL-g-PEG surface is considered to be a promising sensor platform for binding 6 His-tagged proteins thanks to the simplicity and cost-effectiveness of the surface modification protocol, high specificity and nearly quantitative reversibility of the protein binding, and the potential to fabricate microarrays of multiple capture molecules. PMID- 17282365 TI - In vivo Detection of Nitric Oxide in Rat Hippocampus. AB - Nowadays, more and more studies have focused on the physiological and pathological effect of nitric oxide (NO). In this study, we directly measured extracellular NO levels in the hippocampus of rats using NO probe. Simultaneously, the artery blood pressure was recorded. It was found that after the administration of N - nitro-L-arginine methyl ester (L-NAME), the NO signal came down and the artery blood pressure rose. This result is coincident with the theory that the decreasing release of nitric oxide in hippocampus results in vasoconstriction and an increase in artery blood pressure. Furthermore, the release of NO is quantitatively estimated. It shows that NO decreased in 4.5-6nM after the intravenous administration of L-NAME (4-6mg/ kg). PMID- 17282366 TI - A Highly Responsive System for On-line in vitro Assessment of Tissue Growth within MicroPorous Polymer Scaffolds. AB - We have proposed a highly responsive system for the on-line in vitro assessment of tissue growth within microporous polymer scaffolds that obviates any compromise of sample integrity. The system's function is based on the sample's loss factor: the imaginary part of the complex permittivity. Reflection measurements were performed using an open-ended coaxial probe and impedance analyzer; they were then related to the sample's complex permittivity by a quasi static model of the probe's aperture admittance. Measurements of saline solutions showed that the real part of permittivity was corrupted by apparent polarization effects. Consequently, we developed a simplified formulation of the imaginary part of the Hanai-Wagner effective medium approximation to eliminate its dependence on the real part of complex permittivity measurement. This formulation allows the sample's cell concentration to be determined. The variation of a sample's cell concentration over time was used as a measure of tissue growth. Measurements in the frequency range of 10-200 MHz were performed on micro-porous polymer scaffolds seeded with progressively greater number of cells. Results demonstrated that the system detected concentration differences between cell seeded scaffolds. PMID- 17282368 TI - Numerical design and experimental analysis of cell-based sensors. AB - A novel numerical design of experimental analysis of cell-based sensors was introduced in the paper. In order to increase the signals to noise ratio and improve the performance of the chips, we analyzed cell-based sensors numerically and experimentally. Since the action potential which is about dozens of milliseconds changes quickly, we demonstrated an improved equivalent circuit model. Based on modeling of the interface between neuron and sensor, we predicted the experimental results. Furthermore, the experiment results indicate that the designed cell-based sensors can detect the extracellular AP, which meets the numerical consequence quite well. PMID- 17282369 TI - High frequency electrically-induced force generation by cellular plasma membranes. AB - Using a novel experimental technique that combines optical trapping with patch clamp and fluorescence photometry, we provide preliminary evidence that native biological membranes are capable of electrically-induced piconewton level force generation in the absence of specialized transmembrane proteins. Force generation is dependent on membrane tension and the transmembrane electrical potential. Salicylate diminishes and presence of prestin, a transmembrane protein found in cochlear outer hair cells, enhances force generation. PMID- 17282367 TI - BAEC adhesion analysis using Thickness Shear Mode sensor. AB - A Thickness Shear Mode (TSM) sensor of which acoustic shear wave has a nano-scale penetration depth was used in detecting biological activities of living cells. The initial cell adhesion process was characterized by analyzing multi-harmonic responses of the TSM sensor. A suspension of bovine aortic endothelial cells (BAECs) was placed on the TSM sensor, and changes in impedance magnitude during sedimentation and attachment processes were monitored. For the validation of cell adhesion, the sensor surface was rinsed at various time points during the adhesion process, and the number of cells remaining attached was counted. By comparing sensor signals with the independently measured cell adhesion, sensor readings were correlated with physical adhesion process. In addition, by coating the TSM sensors with gelatin and by blocking the integrin bindings with Arg-Gly Asp peptides (RGD), we investigated cell adhesion process under different environments. The time course of sensor readings were characterized with delay time, slope and maximum value of impedance magnitude changes. This study demonstrates the ability of the TSM sensor to detect distinct phases in the cell adhesion process. PMID- 17282370 TI - Microfabricated Cell-based Biosensor Arrays. AB - Here, we described the fabrication using photolithography of poly(ethylene glycol) (PEG)-based hydrogel microstructures encapsulating viable mammalian cells on glass and silicon substrates. Substrates were treated with 3-(trichlorosilyl) propyl methacrylate to form pendant acrylate group to covalent link the hydrogel microstructure. Cells were encapsulated in arrays of cylindrical hydrogel microstructures 600 and 50 μm in diameter and viability assays demonstrated that encapsulated cells remained viable after photoencapsulation. These microstructures had clearly defined, three-dimensional structure without any residual cells remaining surface and no delamination of hydrogel elements from functionalized substrate occurred in aqueous environment for over a week. By changing spin-coating rates and feature sizes of photomasks, we could create cell containing microstructures with aspect ratios ranging from 0.12 to 1.4. In case of 50 μm hydrogel microstructure, number of cells could be limited to 1 or 2 cells per element and array consisting of 400 elements could be fabricated in a square of 2 mm2. These cell-containinghydrogel microstructures were also successfully fabricated in poly(dimethylsiloxane) microchannels to create optical biosensor arrays of individually addressable single or multiple cell- containing hydrogel microstructures with potential applications in drug screening or pathogen detection. PMID- 17282371 TI - Effects of cardiac anisotropy on three-dimensional inverse activation time imaging: a cellular-automaton-based model study. AB - The aim of the present study was to examine the effect of cardiac anisotropy on the ECG activation time imaging solutions using a cellular-automaton-heart-model based approach. The anisotropic heart model was used in forward pacing simulation while anisotropic and isotropic heart models were used in inverse procedures, respectively. Twenty-four sites throughout the ventricles were paced and the corresponding cardiac activation sequences were inversely estimated. The inverse solutions of activation time using anisotropic or isotropic heart model were compared. The computer simulation results suggest that the cardiac anisotropy does not seem to have significant influence on the inverse estimation of activation time using the present 3D heart-model- based inverse imaging approach during single paced activation. PMID- 17282372 TI - Imaging of bioelectric sources in the heart using a cellular automaton model. AB - The approach to solve the inverse problem of electrocardiography presented here is using a computer model of the individual heart of a patient. It is based on a 3D-MRI dataset. Electrophysiologically important tissue classes are incorporated using rules. Source distributions inside the heart are simulated using a cellular automaton. Finite Element Method is used to calculate the corresponding body surface potential map. Characteristic parameters like duration and amplitude of transmembrane potential or velocity of propagation are optimized for selected tissue classes or regions in the heart so that simulated data fit to the measured data. This way the source distribution and its time course of an individual patient can be reconstructed. PMID- 17282373 TI - Simulation of intracardial potentials with anisotropic computer heart models. AB - To date, most interests in simulation studies with whole heart models are in body surface or epicardial potentials in order to compare the results with measurements in experimental and clinical practices. The focus of this study is paid on intracardial potentials as they are comparable with measurements during the invasive Electrophysiological Study (EPS) and the catheter ablation, which are becoming a dominant means in the therapy of arrhythmias. In this paper, simulations are implemented based on anisotropic computer heart models and a simulation system previously developed. The heart model consists of about 50,000 discrete cell elements with 1.5 mm spatial resolution. An algorithm in computing intracardial potentials inside the four cavities of the heart is developed. The HRA (High Right Atrium), HIS (His Bundle), RVA (Right Ventricle Apex), and CS (Coronary Sinus) potentials are shown and compared between a normal heart model and a heart model with the Wolff-Parkinson-White (WPW) Syndrome. By employing the intracardial potential parameters and morphology, the position of the accessory pathway between the atria and ventricula in the WPW computer heart model can be qualitatively located. It is concluded that the simulated intracardial potentials based on an anisotropic whole heart model can well approximate the realistic intracardial potentials. PMID- 17282374 TI - Multiple Dipole Sources Localization from the Scalp EEG Using a High-resolution Subspace Approach. AB - We have developed a new algorithm, FINE, to enhance the spatial resolution and localization accuracy for closely-spaced sources, in the framework of the subspace source localization. Computer simulations were conducted in the present study to evaluate the performance of FINE, as compared with classic subspace source localization algorithms, i.e. MUSIC and RAP-MUSIC, in a realistic geometry head model by means of boundary element method (BEM). The results show that FINE could distinguish superficial simulated sources, with distance as low as 8.5 mm and deep simulated sources, with distance as low as 16.3 mm. Our results also show that the accuracy of source orientation estimates from FINE is better than MUSIC and RAP-MUSIC for closely-spaced sources. Motor potentials, obtained during finger movements in a human subject, were analyzed using FINE. The detailed neural activity distribution within the contralateral premotor areas and supplemental motor areas (SMA) is revealed by FINE as compared with MUSIC. The present study suggests that FINE has excellent spatial resolution in imaging neural sources. PMID- 17282375 TI - Hybrid Weighted Minimum Norm Method A new method based LORETA to solve EEG inverse problem. AB - This Paper brings forward a new method to solve EEG inverse problem. Based on following physiological characteristic of neural electrical activity source: first, the neighboring neurons are prone to active synchronously; second, the distribution of source space is sparse; third, the active intensity of the sources are high centralized, we take these prior knowledge as prerequisite condition to develop the inverse solution of EEG, and not assume other characteristic of inverse solution to realize the most commonly 3D EEG reconstruction map. The proposed algorithm takes advantage of LORETA's low resolution method which emphasizes particularly on 'localization' and FOCUSS's high resolution method which emphasizes particularly on 'separability'. The method is still under the frame of the weighted minimum norm method. The keystone is to construct a weighted matrix which takes reference from the existing smoothness operator, competition mechanism and study algorithm. The basic processing is to obtain an initial solution's estimation firstly, then construct a new estimation using the initial solution's information, repeat this process until the solutions under last two estimate processing is keeping unchanged. PMID- 17282376 TI - Visualization and Post-processing of 5D Brain Images. AB - Visualization plays a central role in the presentation and interpretation of medical image data. Radiologists and surgeons must be able to accurately interpret the data for diagnosis and surgical planning. The data obtained from many imaging systems can contain functional as well as structural information producing 4D datasets. In some cases this can extend to 5D when the image provides spectral information. Generally speaking, more information can be revealed in 5D than 4D imaging. Although several approaches are available to visualize 4D medical data, there is limited research on the visualization of 5D medical data. To present 5D medical datasets efficiently on a 2D screen provides considerable challenges to visualization. In this paper, a 5D brain EIT (Electrical Impedance Tomography) dataset is used as a case study. The relationship and differences between multiple dimensional dataset visualization in different areas are analysed. A statistical post-processing method is then adopted to concentrate information included in the fifth dimension. A scheme to visualize 5D medical dataset is proposed and results are shown based on a simulated dataset. PMID- 17282377 TI - Ultrasonic imaging of myocardial vibrations associated with coronary artery disease. AB - Coronary artery disease (CAD) is a major cause of mortality in the western world. Although progress has been made in recent years for the noninvasive diagnosis of CAD, a widely available, inexpensive and effective diagnostic solution remains elusive. We have developed a novel ultrasound-based technology to detect and analyze the myocardial vibrations associated with diastolic murmurs produced by CAD. Conventional ultrasound imaging systems suppress these vibrations. We have developed algorithms to process the raw ultrasound data and isolate these vibrations and integrated them into a programmable ultrasound system for real time vibration imaging. In preliminary results from clinical studies of patients with CAD, we have observed localized areas of vibrations in the neighborhood of the stenosed coronary artery. The vibrations are narrowband with frequency >200 Hz, and appear to have harmonic components, thus indicating reasonance phenomena potentially with nonlinear mechanisms involved. No such vibrations were observed in normal subjects. Analysis of myocardial vibrations could provide a noninvasive diagnostic test for CAD that overcomes many of the limitations of conventional noninvasive tests. Potentially, this technology could provide a new way of evaluating CAD and cardiac function. PMID- 17282378 TI - Evaluation of patient-centered electronic health record to overcome digital divide. AB - Advances and wide acceptance of information and communication technology (ICT) have made development and implementation of web-based electronic personal health records (PHRs) more feasible than ever before, and previous studies have demonstrated some of its potential and promises. However, this type of ICT dependent approach inherits its own vulnerabilities of exposing the society to digital divide, commonly described as the gap that exists among individuals and communities with regards to the haves and have-nots of information and modern communications technologies. To address these concerns and improve healthcare outcomes, we have developed and customized a web-based patient-centered electronic PHR, named the Personal Health Information Management System (PHIMS), and evaluated the system at the Everett Housing Authority, which provides housings for low-income ncome families and elderly or disabled populations. A preliminary study demonstrates that 92% of the participating residents are satisfied with the PHIMS system in general. Some of the residents found PHIMS records very useful for their clinic visits. PMID- 17282379 TI - Recovery of Metabolomic Spectral Sources using Non-negative Matrix Factorization. AB - 1H magnetic resonance spectra (MRS) of biofluids contain rich biochemical information about the metabolic status of an organism. Through the application of pattern recognition and classification algorithms, such data have been shown to provide information for disease diagnosis as well as the effects of potential therapeutics. In this paper we describe a novel approach, using non negative matrix factorization (NMF), for rapidly identifying metabolically meaningful spectral patterns in1H MRS. We show that the intensities of these identified spectral patterns can be related to the onset of, and recovery from, toxicity in both a time-related and dose-related fashion. These patterns can be seen as a new type of biomarker for the biological effect under study. We demonstrate, using k-means clustering, that the recovered patterns can be used to characterize the metabolic status of the animal during the experiment. PMID- 17282380 TI - Incorporating temporal information for ventricular contour detection in echocardiographic image sequences. AB - A novel way to incorporate temporal information with level set algorithm is proposed to counter the dropout problem when detecting ventricular contours in echocardiographic raphic image sequences. The temporal information ided embed- ed into the speed term of the level set equation. By identifying the ventricular contours as strong or weak segments, the weak segments are strengthened based on temporal information from neighboring frames. Hence disrupted heart wall boundary structure information due to dropout can be recovered. A Gaussian Mixture Model (GMM) is employed to compute thresholds separating the segments. A weight and a strengthening ng factor are used to control the information recovery process. Experimental results show the proposed method exhibits good performance when tracking the ventricular boundary in real echocardiographic data. PMID- 17282381 TI - Cardiac autonomic function in older adults with sleep-disordered breathing. AB - We searched for possible associations between various measures of severity of sleep-disordered breathing (SDB) and indices of cardiac autonomic function in older subjects (>60 years). Twenty four overnight unattended homebased based polysomnograms obtained from the Sleep Heart Health Study were analyzed using spectral analysis. For each subject, six autonomic indices reflecting heart rate variability were quantitatively determined during wakefulness, REM sleep and non REM sleep. Each individual autonomic marker was regressed against each of 4 measures of SDB, including the respiratory disturbance index (RDI), respiratory oscillation index, cumulative oxygen desaturation, and arousal index. In general, we found no correlation between any of these measures of SDB severity and each of the autonomic indices. However, mean heart rate was found to decrease as RDI increased. As well, the ratio of low-frequency to high-frequency power (LHR) decreased with increasing RDI. Contrary to previous reports, our preliminary findings suggest that sympathetic activity decreases with increasing severity of SDB. This paradoxical association between SDB and cardiac autonomic function may be the result of natural compensatory mechanisms at work, allowing some subjects with SDB to be protected from systemic hypertension or other cardiovascular diseases. Supported in part by NIH Grants HL076375, EB001978, HL63463 and HL53941. PMID- 17282382 TI - Robust respiratory flow estimation using statistical properties of tracheal sounds. AB - For any respiratory sound analysis or assessment, respiratory flow must also be measured simultaneously with the sounds. However, due to difficulties and/or inaccuracy of the most flow measurement techniques, several researchers have attempted to estimate flow from respiratory sounds. However, all of the proposed methods heavily depend on the availability of different rates of flow for calibration of the model, which makes their use limited by a large degree. In this paper, a robust and novel method for estimating flow using entropy of the band pass filtered tracheal sounds is proposed. The proposed method is independent of the flow rate chosen for calibration; it requires only one breath for calibration and can estimate any flow rate even out of the range of calibration flow. The method was tested on data of 10 healthy subjects at three different flow rates above 15 ml/s/kg. The estimation error was found to be 7.3 ± 2.0% and 7.4 ± 3.2% for inspiration and expiration phases, respectively. PMID- 17282383 TI - Removal of Ocular Artifacts from EEG: A Comparison of Adaptive Filtering Method and Regression Method Using Simulated Data. AB - We recently proposed an adaptive filtering method for removing ocular artifacts from EEG recordings. In this study, the accuracy of this method is evaluated quantitatively using simulated data and compared with the accuracy of the time domain regression method. The results show that when transfer of ocular signal to EEG channel is frequency dependent, or when there is a time delay, the adaptive filtering method is more accurate in recovering the true EEG signals. PMID- 17282384 TI - A robust human identification by normalized time-domain features of electrocardiogram. AB - This study investigates the possibility of using the normalized time-domain features of Electrocardiogram (ECG) for improving the capability of human identification. For this purpose, we measured lead-1 rest ECG (normal heart rate) and physically active one (fast heart rate) from the pre-selected group. The characteristic points on the ECG waveform, P, QRS, T are extracted in terms of its time location and the ECG data is reconstructed in beat-by-beat basis by Fourier synthesis. R-T interval, Q-T interval, and QRS interval on the reconstructed ECG sequence in rest and in physical active mode are computed. The beat-by-beat based discriminatory analysis is performed on the rest and physical active ECG data by applying Malalanobis distance between these intervals. PMID- 17282385 TI - Enhanced estimation of motor unit number and distribution using linear least squares modeling. AB - MUNE methods estimate the typical motor unit (MU). The typical MU amplitude is divided into the compound muscle action potential (CMAP) amplitude to obtain the MUNE. A novel method is proposed in which the CMAP is modeled as a linear least squares (LLS) fit of the MU waveforms. The sum of the coefficients in the model is the motor unit number estimate. Each coefficient represents the count of the different MU estimates. The MU waveforms are clustered into groups with similar morphology and a representative waveform is calculated for each cluster. These representative waveforms are used in the LLS model. PMID- 17282386 TI - Practical Consideration about Cost Functions of Spatial Independent Component Analysis in Medical Image Processing. AB - Independent component analysis (ICA) is widely used for signal separation in various fields. However, low signal to noise ratio (SNR) of data sometimes causes failures in component estimation. We have proposed a spatial ICA-based method for extracting a blood-related component from medical images measured with positron emission tomography (PET) to omit arterial blood sampling, in which a cost function was designed in consideration of statistical properties of components. In this study, spatial ICA with the proposed cost function or kurtosis, a conventional cost function, was applied to real PET images measured with three kinds of radiopharmaceuticals, and the estimation results were compared. The proposed cost function fails to estimate components from the PET data with low SNR because it is sensitive to outliers. Experimental results suggest that a cost function should be selected depending on SNR of data. PMID- 17282387 TI - Study on changes of characteristic parameters of biological tissues impedance spectroscopy in vitro within 5 to 360 min after excision at the frequency range from 1Hz to 1MHz. AB - We constructed an impedance spectroscopy measurement system based on frequency response analyzer. Using four-terminal method, we measured impedance spectroscopy of rabbit different tissues in vitro within 5 to 360 minutes after excision at the frequency range from 1Hz to 1MHz. According to the measurement results, we analyzed the changes of characteristic parameters (Ro, Rinfin, fc and alpha) of different tissues in the time course. The results show that the Cole-Cole model characteristic parameters change notably in the time course. The value of Ro change great especially. For kidney, liver, spleen and heart, the value of Ro reached 700%, 125%, 170% and 200% respectively at the 6 hour after excision. The change of alpha is less than 30% for all tissues. The changes of fc are various remarkably for different tissues, for liver, kidney and heart, the value of fc decreased continually and the decrement reached 60%, 19%, 33% respectively at the end of the measurement. For muscle (longitudinal, transverse) and heart, the value of fc decreased firstly and then began to increase and reached 145% > 155% > 125% at 6 hour after excision. The results of our reaching show the measurement time plays a remarkable effect on the impedance spectroscopy measurement of tissue in vitro. We hypothesized that the dispersion observed in the impedance spectroscopy measurement in vitro between different researchers was partly due to the effect of measurement time. PMID- 17282388 TI - Support Vector Regression Estimation Based on Non-uniform Lost Function. AB - The performances of support vector regression estimation were analyzed. It was found that the insensitive factor epsiv can affect the performance of support vector regression estimation significantly. The noise inside the sample data should be considered in determining the insensitive factor epsiv when support vector regression was employed. A novel support vector regression based on non uniform lost function (NLF-SVR) was proposed to deal with different noise data density function in different region. The formulation and algorithms of computing NLF-SVR were given. The test example showed that the outcomes of NLF-SVR are better than that of conventional SVR. NLF-SVR can be applied in physiological systems modeling. PMID- 17282389 TI - Predict ultrasonic backscatter coefficient in cancellous bone by theory and experiment. AB - The scattering mechanism of ultrasound in cancellous bone is investigated theoretically. The relationship of backscatter coefficient (BSC) in cancellous bone with frequency is analyzed in theoretical and experimental. The results of theory and experiment for cancellous bone of bovine tibiae, human calcaneus in vitro and in vivo showed that BSC is a non-linear function of frequency, increasing with frequency. In general, all curve of BSC can be divided into three sections with different slope. The slopes of the first and third section have a large value, and the slope of second section is flat. A good agreement was obtained in the averaged BSC of experiment and cellular model. Those results suggest that the backscatter signal and BSC have a particularly important action in assessment of cancellous bone status and diagnosis of osteoporosis. PMID- 17282390 TI - Correlation character of ionic current fluctuations in cell membrane ion channels. AB - The gating of ion channels has widely been modeled by assuming the transition between open and closed states is a memoryless process. Nevertheless, the statistical analysis of an ionic current signal recorded from voltage dependence K+ single channel is presented. Calculating the sample autocorrelation function of the ionic current based on the digitized signals, rather than the sequence of open and closed states durations time. The result is shown existence memory. For difference voltage, the ion channel current fluctuation has difference correlation attributions. The result suggests the correlation character of the ionic current fluctuations. Also the possible biological implication of the findings have been discussed. PMID- 17282391 TI - Evoked Potentials Estimation by using Higher Order Adaptive Neural Network filter. AB - Evoked potentials are usually embedded in the ongoing electroencephalogram with a very low signal-to-noise ratio. The neural network filtering technique which has the advantage of complex mapping is one of the applicable methods for evoked potentials estimation. The backpropagation algorithm based on second order statistics is commonly used to adapt neural network filters. However it is easily influenced by additive Gaussian noise. In this study, a neural network filter with a modified back-propagation algorithm for higher order statistics was proposed. With higher-order statistics technique, additive Gaussian noise is suppressed to improve the performance of evoked potentials estimation. PMID- 17282392 TI - Arrhythmia classification with reduced features by linear discriminant analysis. AB - In this study, we proposed 17 input features based on wavelet coefficients for arrhythmia detection and, by applying linear discriminant analysis to these, reduced the feature dimension to be 4. Then, with newly constructed 4 dimension input feature, a multi-layer perceptrons classifier was tried to detect 6 types of arrhythmia beats. For evaluation of input features by linear discriminant analysis, the arrhythmia detection efficiency with these (LDA) was compared to that with original input features (ORG) and that with of input features by principle component analysis (PCA) respectively. When LDA was compared to ORG, the former showed similar or a little higher values than the latter for different types of arrhythmia beats except SVT. And, LDA showed to be persistently higher than PCA. By theses cross-validations, for the detection of several types of arrhythmia beats, the reduction of input feature dimension by linear discriminant analysis was revealed to be prior to that by principle component analysis. Even if LDA was compared to ORG, it maintained the acceptable level efficiency so that the time and computational costs would be expected to be cutdown dramatically. Finally, by the proposed algorithm, we could obtain the good accuracy of arrhythmia detection and that of NSR, SVT, PVC and VF was 99.52%, 99.43%, 98.59% and 99.88%, respectively. PMID- 17282393 TI - Principal Component Regression Approach for QT Variability Estimation. AB - New algorithm for quantifying the variation in the QT interval of ECG recording is presented. The algorithm is based on the Principal Component Regression where the eigenvectors of the data correlation matrix are calculated. The eigenvectors are then used for calculation of the principal components and one of them is selected to represent the information about T wave variation. The algorithm is tested using high speed ECG recording. PMID- 17282394 TI - The separation of metabolizing heat based on independent component analysis. AB - The inner metabolizing status can be measured by surface temperature changes of human. These changes involve lots of heat influence in which metabolic heat production is the most important. Based on processing the data acquired by improved cold stimulation experiment with Independent Component Analysis(ICA), this paper obtains two of main heat component - heat transfer quantity of blood perfusion and heat-production quantity of metabolism. The physiological meaning of these two components is discussed. PMID- 17282395 TI - Classification of Heartbeats based on Linear Discriminant Analysis and Artificial Neural Network. AB - In this paper, we proposed a heartbeat classification algorithm based on linear discriminant analysis and artificial neural network. For the input of classifier, we extracted 275 input features from the first derivative signal of ECG signal and RR interval information and it was reduced to be 6 by LDA. To evaluate the performance of the proposed algorithm, we compared the result of the proposed algorithm with that of fuzzy inference system classifier. MIT-BIH Arrhythmia database were used as test and learning data. The performance of the proposed algorithm was 97.49% for sensitivity, 97.91% for specificity and 96.36% for accuracy. For the extraction of features, the first derivative signal of ECG is used only so that the real-time implementation of this algorithm was possible. And, on account of the reduction of feature dimensionality, the time cost for learning and testing can be expected. PMID- 17282396 TI - Comparison of a Sleep Quality Index between Normal and Obstructive Sleep Apnea Patients. AB - This paper aimed at developing an index, called Sleep Index, to assess the quality of sleep in normal and obstructive sleep apnea (OSA) subjects. The Sleep Index was designed to be directly proportional to the summation of product of the number seconds spent in each stage of sleep and the selected weighting coefficient of each sleep stage. It was also inversely proportional to the product of total number of sleep stage shifts and the total number of seconds spent in all stages of sleep. In order to test the proposed index, data from eleven previously diagnosed sleep apnea subjects (6 females and 5 males; Age: 50 ± 8.94; Body Mass Index (BMI): 31.70 ± 6.97) and 14 normal subjects (8 females and 6 males; Age: 46.43 ± 9.61; BMI: 25.541± 3.061) were used. All the subjects underwent nocturnal polysomnography (NPSG) at an accredited sleep center. Statistical testing of the Sleep Index showed that its mean was significantly different for normal and OSA subjects (p<0.04). The Sleep Index values were higher for normal subjects than for sleep apnea subjects. This was in part due to the higher number of sleep stage shifts in OSA subjects compared to normal subjects. Therefore, higher Sleep Index values reflect better sleep quality. The number of sleep stage shifts should be higher for sleep apnea subjects as they frequently experience sleep arousal and sleep continuity is impaired, resulting in daytime sleepiness. PMID- 17282397 TI - Automatic detection of micro-arousals. AB - In patients suffering from various sleep disorders and some elderly patients, sleep is disturbed with frequent but brief arousal. These events do not cause behavioral awakening, but can lead to excessive day time sleepiness. These brief arousals or microarousals (MAs) can be identified on a standard polysomnogram as a transient abrupt change of frequency, typically in the alpha and extended beta (16-40 Hz) bands. In this paper, we present a novel method to automatically detect MAs. The method is based on using the ideas of segmentation, spectral feature extraction and the identification of EEG epochs containing MA with statistical methods and decisional rules. Full-night EEG recordings from two patients are used to present some initial performance results. For this analysis, the MA events are independently scored by three experienced sleep experts. Results show the method to be promising; however, due to the large inter-scorer variations it may be necessary to tailor the detection threshold to address the varying scorer preferences (address the sensitivity/specificity tradeoffs). PMID- 17282398 TI - Biometric Statistical Study of One-Lead ECG Features and Body Mass Index (BMI). AB - We have studied the electrocardiogram (ECG) as a potential biometric for human identity verification. This research investigates the relationship between ECG biometric features and body mass index (BMI) using correlation analysis and linear regression methods. Using our ECG database of 168 normal healthy people (113 females and 55 males), we studied normalized features extracted from a one lead, resting, palm ECG. The results showed that normalized ECG biometric features explain 25.3% of the variability of the BMI. ECG features of males better correlate with the BMI model than those of females. Furthermore, we calculated correlation coefficients and R-square changes to analyze the correlations between extracted features and the BMI and to indicate the most significant feature as a predictor of BMI among all ECG biometric features. PMID- 17282400 TI - Localization of brain abnormal signal sources using blind source separation. AB - An effective and simple algorithm for localization of abnormal sources of the EEG signals within the brain has been developed here. In this method the signals are separated first, then the estimated independent components are lowpass filtered and normalized. In the next stage the correlation values between the estimated sources and the electrode signals are measured. On the other hand the sources with known locations are separated offline using narrowband bandpass filters. Finally, as the main contribution of the paper the mixing matrix is estimated using the information about the known sources and the estimated sources. The locations of the unknown sources are then measured with respect to the columns of the mixing matrix and the geometrical properties of the head and electrode locations. PMID- 17282399 TI - Is P50 an epiphenomenon? AB - The mid-latency auditory evoked response (MLAER) consists of the P50, N100 and P200 components. P50 is widely used to examine sensory gating. There is growing evidence that phase-reorganization of the oscillatory components comprising EEG activity, and especially in the 4-8 Hz (theta) band, is responsible for MLAER generation. Consequently, all or part of the MLAER may be an epiphenomenon, indicating intervals of increased phase reorganization. In this study, we investigated the nature of P50. AEPs were obtained from 14 normal subjects using a double stimulus paradigm, and each artifact-free trial was decomposed into its constituent oscillatory components. Single trials were classified into 16 groups on the basis of the presence of N100/P200-like activity and the phase at stimulus onset in the 4-8 Hz band. It was found that P50 consists of low-frequency (theta) and high frequency (gamma) activity. The appearance of P50-related theta activity was closely related to the presence of N100. The P50-related theta activity appeared only when the theta activity goes through a positive zero crossing at the moment of stimulus presentation. Thus it appears that the theta component of the P50 should be considered as an epiphenomenon. PMID- 17282401 TI - Detrended Fluctuation Analysis: A Suitable Long-term Measure of HRV Signals in Children with Sleep Disordered Breathing. AB - On the body surface the electric field generated by the cardiac muscles consists of electric potential maxima and minima that increase and decrease during each cardiac cycle. The recording of these electric potentials as a function of time is called electrocardiography, and the resulting signal is called the electrocardiogram (ECG). The ECG signal is used extensively as a low cost diagnostic tool to provide information concerning the heart's state of health. Reliable and accurate detection of the QRS complex and R wave peak in ECG signals is essential in computer-based ECG analysis. In this paper we evaluate the significance of Detrended Fluctuation Analysis (DFA) for studying heart rate variability in children with sleep disordered breathing. An Enhanced Hilbert Transform (EHT) algorithm was used to derive the Heart Rate Variability (HRV) signal. We compare the DFA values with Approximate Entropy and Poincare Plots of HRV signals as these are very useful in characterization and visualization of HRV data. Our data demonstrated differences in DFA parameters between periods of normal and abnormal breathing and also between sleep stages. These results suggest that DFA is suitable for the long-term analysis of non-stationary time series such as HRV signals and may also be applied in the detection of sleep disordered breathing. PMID- 17282402 TI - Variable selection using genetic algorithm for analysis of near-infrared spectral data using partial least squares. AB - Genetic algorithm is used to perform variable selection to determine the ranges of wavelengths in NIR spectral data suitable to be used as predictors in multivariate calibration model via partial least squares. The NIR spectral data consists of three components of active substances, namely human serum albumin (HSA), γ-globulin and glucose. The wavelength selection is able to improve the calibration model by selecting the wavelengths that contains information or correlated with the concentration of substances, while others non-chosen wavelengths, which contribute no information or contain noises, are excluded from the calibration model. PMID- 17282403 TI - Researching on selectivity mechanism of potassium channel to monovalent cations in signal transduction. AB - Ion channels bear the same relation to electrical signaling in nerve, muscle, and synapse as enzymes bear to metabolism. The potassium channel is one of the most important type. Potassium ion is at least 10,000 times more permeant than sodium ion, remaining to be an open question of potassium channels. To elucidate the mechanism of ion selectivity at atomic level, the authors performed density functional theory to calculate the position energy on the basis of the X-ray structure of the KcsA channel. In the viewpoint of statistic thermodynamics, the two most readily permeant ions, potassium and rubidium ions, can pass through the selectivity filter. In contrast, sodium ions are preferring to stay in site 2 which can not pass through the channel. The energy barrier difference between the potassium ion and sodium ion is 35.15 kcal mol-1. The energy barrier difference between the potassium ion and rubidium ion is 14.44 kcal mol 1. The energy barrier difference between the potassium ion and ammonium ion is 21.97 kcal mol-1. The results are qualitatively consistent with the experimental data. It is remarkable that the system, involving in 269 atoms, is much lower than the system involved in MD simulation which is on the order of 41000 atoms. PMID- 17282404 TI - The Study About the Reduction of the Stimulus Artifact Using PSR Filter. AB - In order to reduce the stimulus artifact, which is contaminated in the initial segments of the Transient Evoked Otoacoustic Emission(TEOAE) and inhibited the detection of high frequency cochlear responses, an artifact reduction technique that draws on Predictor-Subtracter-Restorer filter for TEOAE signal is firstly proposed. Compared with Derived Nonlinear Response (DNLR) method, the result showed empirically that this proposed method not only reduced the stimulus artifact, but also reserved the useful information of TEOAE at high frequency. PMID- 17282405 TI - Itakura Distance: A Useful Similarity Measure between EEG and EOG Signals in Computer-aided Classification of Sleep Stages. AB - Sleep is a natural periodic state of rest for the body, in which the eyes usually close and consciousness is completely or partially lost. Consequently, there is a decrease in bodily movements and responsiveness to external stimuli. Slow wave sleep is of immense interest as it is the most restorative sleep stage during which the body recovers from weariness. During this sleep stage, electroencephalographic (EEG) and electro-oculographic (EOG) signals interfere with each other and they share a temporal similarity. In this investigation we used the EEG and EOG signals acquired from 10 patients undergoing overnight polysomnography with their sleep stages determined by certified sleep specialists based on RK rules. In this pilot study, we performed spectral estimation of EEG signals by Autoregressive (AR) modeling, and then used Itakura Distance to measure the degree of similarity between EEG and EOG signals. We finally calculated the statistics of the results and displayed them in an easy to visualize fashion to observe tendencies for each sleep stage. We found that Itakura Distance is the smallest for sleep stages 3 and 4. We intend to deploy this feature as an important element in automatic classification of sleep stages. PMID- 17282407 TI - Quantitative evaluation of distant student psychophysical responses during the e learning processes. AB - Using 4 biometric sensors, including GSR (Galvanic Skin Response), BVP (Blood Volume Pulse), EKG (Electro Cardio Grapy) and EEG (Electro Encephalon Grapy), this paper proposes to attempt to correlate the presentation of relaxing, engaging or stressful content to the subjective measures provided by participants in experiments. Once the participant interacts with content from one of the 3 conditions, they may or may not be selectively relaxed, engaged or stressed, and their scores on a psychological self-questionnaire (STAI: State-Trait Anxiety Inventory) should show that. From correlating the subjective ratings with the experimental conditions, is proposed to allow to develop algorithms that can be used to classify learners' affective state during synchronous or asynchronous coursework. It is proposed that the algorithm could be used synchronously for the teacher to get student feedback in real time. PMID- 17282406 TI - Statistical analysis of visual evoked potentials in optic neuritis and ischemic optic neuropathy subjects. AB - An effective and clinically relevant parameter for differentiating ischemic optic neuropathy (ION) and optic neuritis (ON) patients using the Visual Evoked Potentials (VEPs) has been identified. In this study, statistical analysis has been carried out on time domain parameters of the VEP waveforms recorded for ION (17 patients) and ON (35 patients) groups. The ratio of the amplitude of P100 component of affected eye to fellow eye showed no significant difference between the two groups. However, the mean P100 absolute latency component of ION patients was found to be significantly (p<0.001) shorter than that of ON patients. This parameter will help the neurologist to clearly classify the diseased patients and help them in early therapy planning. PMID- 17282408 TI - Validity of polygraphs. AB - Electrodermal Activity is extensively used for measuring human emotions. Validity and reliability have been questioned by some researchers. This paper reports on highly controlled experiments to determine the validity of electrodermal al activity for measuring human emotions. The authors were unable to determine the validity of electrodermal activity for measuring human emotions. Inter and intra subject variation was very high. PMID- 17282409 TI - Bayesian applications to longitudinal analysis on medical data with discrete outcomes. AB - Many prediction studies of medical research lead to discrete longitudinal data with repeated measurement and categorical outcomes. Therefore the traditional likelihood-based methods for continuous outcome measures are no longer suitable. With the development of modern computing technologies and improved scope for estimation via iterative sampling methods, Bayesian analysis is becoming increasingly popular among biostatisticians. Markov Chain Monte Carlo (MCMC), for the implementation of Bayesian methods has rendered the implementation of complex Bayesian models a reality. In addition, the availability of software like WinBUGS has made the utilization of MCMC straightforward. In this study, we developed a full Bayesian version of generalized linear models for binary longitudinal data and applied it to a longitudinal prediction study of Alzheimer's disease conducted at New York University School of Medicine. PMID- 17282410 TI - Time Consuming Numerical Model Calibration Using Genetic Algorithm (GA), 1 Nearest Neighbor (1NN) Classifier and Principal Component Analysis (PCA). AB - Single Objective Genetic Algorithm (SGA) optimization process usually needs a large number of objective function evaluations before converging towards global optimum or a near-optimum. The SGA is used as automatic calibration method for a wide range of numerical models. However, the evaluation of the quality of solutions is very time-consuming in many real-world numerical model calibration problems. The algorithm SGA-1NN-PCA, an effective and efficient dynamic approximation model to reduce the number of actual fitness evaluations, is presented in this paper. Training data of 1NN classifier are produced from early generations. 1-Nearest Neighbor (1NN) classifier is used to predict objective function values for evaluations. Principal Component Analysis (PCA) linearly transforms high-dimensional optimization parameters into low-dimensional optimization parameters to save test time for 1NN. The test results show that the proposed method only requires about 25 percent of actual fitness evaluations of the SGA. PMID- 17282411 TI - Wavelet Approach for ECG Baseline Wander Correction and Noise Reduction. AB - Electrocardiographic (ECG) analysis plays an important ortant role in safety assessment during new drug development and in clinical diagnosis. The pre processing of ECG analysis consists of low-frequency baseline wander (BW) correction and high-frequency artifact noise reduction from the raw ECG. We present approaches for BW correction and de-noising based on discrete wavelet transformation (DWT). We estimate the BW via coarse approximation in DWT with recommendations for how to select wavelets and the maximum depth for decomposition ition level. We reduce the high-frequency noise via Empirical Bayes posterior median wavelet shrinkage method with leveldependent ependent and position dependent thresholding values. The methods are applied to a real example. The experimental results indicate that the proposed method can effectively remove both low-and high-frequency noise. PMID- 17282412 TI - Spectral analysis of R wave attenuation and heart rate variability for detection of cheyne stokes breathing. AB - Spectral analysis was carried out on the R-Wave Attenuation (RWA) trend and Heart Rate Variability (HRV) series, derived from the polysomnographic Electrocardiogram (ECG) of the subjects with and without Cheyne Stokes Breathing. Nocturnal polysomnography was performed on 16 Normal subjects and 7 subjects with Cheyne Stokes Breathing (CSB) patients. The polysomnographic ECG data was divided into fifteen minute epochs for analysis. These epochs are processed to obtain the RWA. Hilbert Transform based algorithm [4] was used for QRS detection. Power spectrum of RWA and HRV are computed for each clip by using Welch's averaged periodogram method. HRV is sensitive to REM sleep as well and hence not specific to sleep apnea [12]. Hence the parameters derived from HRV alone cannot be used as diagnostic markers. Hence a combined detection scheme which uses parameters derived from RWA and HRV power spectrum is used in the proposed method to increase detection accuracy. This method produced a sensitivity of 84.75% and specificity of 87.03% in the training set and sensitivity of 85.78% and a specificity of 87.19% in the test set. PMID- 17282413 TI - Can acoustic vowel space predict the habitual speech rate of the speaker? AB - This study aims to find whether the acoustic vowel space reflect the habitual speaking rate of the speaker. The vowel space is defined as the area of the quadrilateral formed by the four corner vowels (i.e.,/i/,/æ/,/u/,/α) in the F1F2- 2 plane. The study compares the acoustic vowel space in the speech of habitually slow and fast talkers and further analyzes them by gender. In addition to the measurement of vowel duration and midpoint frequencies of F1 and F2, the F1/F2 vowel space areas were measured and compared across speakers. The results indicate substantial overlap in vowel space area functions between slow and fast talkers, though the slow speakers were found to have larger vowel spaces. Furthermore, large variability in vowel space area functions was noted among interspeakers in each group. Both F1 and F2 formant frequencies were found to be gender sensitive in consistence with the existing data. No predictive relation between vowel duration and formant frequencies was observed among speakers. PMID- 17282414 TI - Characteristic Parameters of MTF of the Retina-Brain System. AB - [Objective] To search parameters characterizing the MTF curve of retina-brain system of the human eye for distinguishing eye disease use. [Method] Suppose the MTF can be expressed by (for symmetric MTF) or (for asymmetric MTF). Let y=ln(MTF), x=lnf, the above formula can be transformed into y=k1x+... (for symmetric MTF) or y=k1'x+...(for asymmetric MTF).Parameters kis(or ki's) are determined by curve fitting from experimental data and used as discriminating indices to indicate various eye diseases. The effectivity of the curve fitting is evaluated by F test.[Result] The fitting parameters and the peak frequencies, fc, of MTF for normal eyes and eyes with diseases are shown in table 1 with corresponding F value and F value under 0.01 confidence level. The experimental data are taken from Wang's paper for normal eyes, and Fang's paper for eyes with diseases.[Conclusion] It seems that the parameters kis (or ki's) can be used as the indices to distinguish eye diseases because they are remarkably different for normal and various eye diseases. In curve fitting, there are reasons to use cubic equations for symmetric MTF (as in the case of cataracts) and quadratic equation for asymmetric MTF (as in the case of amblyopia). PMID- 17282415 TI - The psychological and physiological effects of light and colour on space users. AB - The impact of colour and light conditions on our emotional and physical health and wellbeing is gaining greater importance in our urban societies. While large resources are allocated for well designed buildings with the right choice of colour and lighting conditions, there are little scientific evidence that supports these choices. The aim of this research was to determine the impact of different colours and lighting conditions on people, using non-invasive means. Close correlations between cardiac activity, our emotions and health are well reported in literature and hence it is expected to be a good measure of environmental conditions on people. Electrocardiogram (ECG) is the non-invasive recording of the cardiac activity. Thus, this paper reports experimental research conducted where changes in ECG were measured when the participants were exposed to different colour and light conditions. The results of these experiments show that there is a change in heart rate (HR) due to change in colour and lighting conditions. PMID- 17282416 TI - Empirical mode decomposition applied to laser Doppler flowmetry signals : diagnosis approach. AB - Empirical Mode Decomposition (EMD) is a recently introduced tool for decomposing signals into so-called intrinsic mode functions (IMF). These IMF represent the data by means of oscillating waves with local zero mean. In some sense the decomposition can be compared with a time-varying filter bank, i.e., signals are decomposed using band limited filters with band widths that vary in time. The main attribute of EMD compared to other time-frequency tools is that it does not use any predetermined filters or transforms. It is therefore a self-contained method that preserves the physical properties in the separate IMF, explaining why it has been successfully applied in many engineering fields. This method is applied here on laser Doppler flowmetry signals and particularly on the hyperemia signals. Two interested hyperemia parameters are the maximum perfusion value and the corresponding time instant of appearance. Accurate values parameters are determined from the fifth IMF component. Computing these parameters allows us to improve diagnosis of some pathologies as peripheral arterial occlusive diseases. PMID- 17282417 TI - Nanostructured lipid carriers as vehicles for transdermal iontophoretic drug delivery. AB - The aim of the present work was to assess the merits of nanostructured lipid carriers (NLCs) as vehicles for transdermal iontophoretic drug delivery. For the measurements, either a model drug (triamcinolone acetonide acetate, TAA) or a lipophilic fluorescent probe (nile red, NR) was encapsulated into NLCs. The NLCs with sizes of 100 nm and 350 nm diameter were prepared by high-pressure homogenization technique. The particle size with polydispersity index (PDI), zeta potential and morphology were examined by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM). In vitro penetration studies involved passive penetration and iontophoresis for control (TAA ethanol solution) and TAA-NLCs formulations. Confocal laser scanning microscopy (CLSM) was employed to visualize the distribution of NR-NLCs after skin permeation. The overall results reveal the benefits of the combined use of iontophoresis and NLCs in improving skin penetration parameters. The NLCs with a size of 100 nm seem to be promising for iontophoretic delivery as they have shown maximum enhancement ratio and skin deposition. This is the first report of the use of NLCs as vehicles for transdermal iontophoretic drug delivery. PMID- 17282419 TI - The Biological Effect of the NanoTiO2and Its Toxicity. AB - The proliferation behavior of the person's liver cell under actions of the nanoTiO2has been looked into by 3-(4,5-dimethylthiazol 2-yl)-2,5 diphenyltetrazolium bromide (MTT) colorimetric method of Mosmann. In this case we first give some elementary properties of the nanoTiO2and do further the liver cell cultures, and add the nano TiO2into the cells. In accordance with biological rules we measure the proliferation state of the liver cell in normal condition. The result obtained show that the influence of the nanoTiO2on the proliferation of the person's liver cell is very small, when compared with that of the control group. We found further out the size of the toxicity of the nanoTiO2to the chick embryo fibroblast (CEF) cells by the MTT colorimetric method. Thus we determine the toxicity for the TiO2s of 100nm and of 1000nm by the toxicology which are all first score (or degree). PMID- 17282418 TI - Biological effects of the carbon nanotubes. AB - The influences of the carbon nanotubes on proliferation state of chick embryo fibroblast cells and toxicity of the nanotubes to the cells have been investigated by 3-(4,5-dimethylthiazol 2-yl)-2,5 diphenylte-trazolium bromide (MTT) colorimetric method of Mosmann and the toxicology. We found that the toxicity of the carbon nanotubes to the chick embryo fibroblast cells is small, it is about first score (or degree). PMID- 17282420 TI - Preparation of Nano-Sized Particles of Collagen II by an Electrostatic Field System. AB - This study described a novel method for preparing nano-sized particles of collagen II by using a high voltage electrostatic field system. The preliminary results showed that the collagen II particles exhibited good sphericity and the particles diameters increased after longer electric field treatment. They were in the range of 208 plusmn 27, 277 plusmn 26 and 467 plusmn 35 nm in diameter at the treatment of 3 kV/cm for 1, 3, and 5 hours respectively at 25degC (collagen concentration was 0.2 mg/ml). Moreover, the particles size increased to 1621 plusmn 49 nm in diameter when the concentration of collagen II was increased from 0.2 mg/ml to 0.5 mg/ml. However, the collagen II was hard to form a nano-particle shape under 30degC at 0.2 mg/ml and 0.5 mg/ml concentration of collagen II. When the temperature increased to 37degC, the collagen II was unable to produce particle, instead, fibrous structures were formed under this temperature setting. This result probably contributed by a entropy driven process which termed fibrillogenesis, a larger force to yield the collagen molecules to self-assemble and then formed collagen fibrils. Incidentally, smoother outer surface of nano particle was observed after 5-hour treatment (collagen concentration was 0.2mg/ml at 25degC). The most important finding was that, no collagen II nano-particles were produced without the treatment of electrostatic field, no matter at either collagen concentration or temperature settings. PMID- 17282421 TI - On electromechanical behaviour of frog sartorius muscles. AB - Considering coupled electromechanical properties of biological soft tissues is an innovative characterization of most soft tissues, this paper reports our experimental observation on electromechanical properties of frog sartorius muscles including the experiment design, test sample preparation, test results and analysis. The experiment results indicate that the electric potential generated in the frog muscle tissues varies with external mechanical loadings. The electric voltage increases with an increase in the frog muscles deformation. This phenomenon is found to be loading cycle and frequency dependency. The experiment results demonstrated that frog muscle tissues can convert their mechanical deformations into electrical signals significantly. The experiment work here is an essential step in understanding the complex electromechanical behaviour of biological soft tissue. It may lead to further research in determining quantitatively the complex electromechanical properties of biological soft tissues. PMID- 17282422 TI - Modeling and simulation of magnetic nanoparticle sensor. AB - Sensitivity and detection limit of a magnetic nanoparticle sensor is modeled and simulated. A micro coil generates an alternating magnetic field which excites magnetic nanoparticles in its vicinity. A concentric sensing coil applies Faraday's law of induction measuring the excited magnetization of the magnetic particles at high frequency. A differential measurement compensates disturbances and the influence of the driving microcoil leaving only the signal caused by the magnetic particles. The sensing system can be used for detection of magnetic nanoparticle labels in immunological point of care diagnostics. The paper shows simulation results for a microcoil system capable of detecting a single superparamagnetic nanoparticle. PMID- 17282423 TI - Capacitive monitoring of the antigen-antibody reactions enhanced by nanogold. AB - An immunosensor for measuring antigen-antibody binding by nanogold particles enhancement was present here. A gold plate electrode was modified by a SAM (self assembled monolayer) of 11-Mercaptoundecanioc Acid. Then sheep anti-rabbit IgG was immobilized onto the end of the 11-Mercaptoundecanioc Acid. With that the gold electrode was exposed to the mixed solution of rabbit IgG and nanogold labeled sheep anti-rabbit IgG. The differential capacitance of the electrical double layer was monitored to detect the antigen-antibody reaction. The result showed the capacity of the electrical double layer by nanogold enhancement was largely increased compared to that in traditional capacitive immunosensor. The detection sensitivity is up to 10nF / μg/ml. PMID- 17282424 TI - Microencapsulation of insulin into biodegradable microcapsules by the high voltage field method. AB - To produce and evaluate sustained microcapsules of insulin made by a novel encapsulation process. The insulin was encapsulated into microcapsules of poly(D, L-lactide co-glycolide) (PLGA) by the high voltage field method. The preparation process was cryogenic, non-aqueous, and did not utilize emulsification. When the ratio of insulin/PLGA was 1:9, the median particle size of insulin microcapsules was less than 200μm, the drug loaded was 8.82%, and the efficiency of encapsulation was 83.2%. Drug release continued over 300h. In conclusion, the process was a novel way to produce insulin microcapsules, and the basic characteristics were satisfactory. PMID- 17282426 TI - Using atuous Algorithm and Modulus Maximum Lines to Detect R-wave of ECG Signal. AB - The R-wave of ECG signal represents the electrical activation of the ventricles, which initiates ventricle contraction, and it belongs to the typical peak value singular signal. An effective way of detecting R-wave in QRS complex of ECG based on a tuous algorithm and modulus maximum lines are presented in this paper. a tuous algorithm doesn't need down sampling and up sampling when in decompose and reconstruction, so it increases the R-wave orientation precision; modulus maximum lines can improve the detection speed dramatically. Experiment shows that, this method can easily realize the accurate orientation and real-time detection of R wave. Due to its simplicity it could be feasible in a real-time testing or clinical heart rate screening. PMID- 17282425 TI - Cell Lysis in SWLA-2 Hybridomas due to 1 kHz AC Electric Fields. AB - This paper describes results involving the percentage cell lysis of SWLA-2 murine hybridomas produced by AC electric field pulses at 1 kHz with pulse widths ranging from 1 ms to 1 second. Cells that had been exposed to the electric fields were cultured and replicate samples were examined at 48 hours to determine the number of viable cells. PMID- 17282427 TI - Clinical laboratories on a chip for human immunodeficiency virus assay. AB - Automated chip-based technologies for clinical diagnosis may have great facilities in the area of life science and medicine. This paper presents the lab on-a-chip design for the assay of HIV, which includes the sample preparation, reaction, and signal amplification module. A laser induced fluorescence system is also designed for real-time monitor of the signals. PMID- 17282428 TI - Fabricating nanofluidic channels and Applying it for single bio-molecule study. AB - In the emerging field of nanobiotechnology, further downsizing the fluidic channels to the nanometer scale is attractive for both fundamental studies and technical applications. The insulation Silicon nitride membrane nanofluidic channel array which have width∼75nm and depth ∼ 100nm and length 50μm were created by focused-ion- beam instrument, theλ--DNA molecules were put inside them and the dynamic characteristics were initial studied, a fluorescence microscopy was used to observe the images. We observed λ--DNA moved inside the nanotrenches which dealt with activating reagent Brij aqueous solution only by capillary force,this will help us to understand more DNA dynamics characteristics and more information about single biomolecule transporting through a nanopore,. PMID- 17282429 TI - A 3-d microelectrodes array microchip applied to cell fusion. AB - A cell-to-cell fusion technique using 3-D microelectrodes array microchip has been developed. It permits cell-to-cell fusion operation in large amount simultaneously. And it needs much lower voltage (alternating voltage and pulse voltage) than the conventional cell fusion techniques. An array of 16 (4×4) microelectrodes can be fabricated on a 1×1cm silicon wafer. And an experimental system, including circuit control unit, temperature control unit,etc.,has been developed to fuse cells. The alternating voltage is applied to the electrodes makes cells in alignment and in pairs firstly. Dielectrophoresis (DEP) force is used to form cell pairs in the microchip and makes cell pairs contact each other tightly. And then fusion of the cell pairs is induced by electric pulse is applied between electrodes. Microelectrodes of 8μm carbon fiber are used to test the feasibility of the proposal experimental system, Human hepatocarcinoma SMMC-7721 cells are used as specimens. It's observed that SMMC 7721 cells formed cell pairs and fused successfully. PMID- 17282430 TI - Suggested shape for a first generation endovascular untethered microdevice prototype. AB - Shape design optimization for an untethered microdevice meant to navigate in the human bloodstream is studied based on previous variational Finite Element (FE) work done. The suggested shape for a first generation prototype is a prolate spheroid design, which enables to minimize the drag force and to maximize the use of the MRI's magnetic gradients. PMID- 17282431 TI - Research Progress of Subretinal Implant based on Electronic Stimulation. AB - Subretinal prosthesis is one kind of retinal prosthesis, which means that a microimplant based on MEMS technology is inserted in the subretinal space to stimulate the optic nerve and elicit an electrical-evoked response on the cortical region. The subretinal implant is made up of extraocular part and intraocular part. As an important part, the latter consists of accessorial setting and stimulation chip that contains microphotodiode array (MPDA) and microelectrodes. The paper main body is made up of four parts. Firstly significance of the retinal prosthesis is given out;secondly fundamentals on both in retina physiology and retinal prosthesis theory are introduced simply. Then the key segment about the subretinal microimplant is presented in detail. In the third segment, first of all is its design concept, the second is fabrication of MPDA which consists of several parts. First is microscopic configuration, electric prototype schematic and chip image COMS. The second is detailed fabrication flow with several special materials. Then is situation of its dimension. The fourth segment presents challenge and outlook. PMID- 17282432 TI - A low-profile three-dimensional silicon/parylene stimulating electrode array for neural prosthesis applications. AB - This paper describes a low-profile three-dimensional silicon/parylene microelectrode array as basis for practical neural prostheses for use in the central nervous system. The circuit areas of the silicon probes, containing mixed signal CMOS circuitry for neural stimulation/recording, can be folded over to reduce the overall height of the microassembled array above the cortical surface. The low- profile structure is implemented using multiple gold beams spaced by orthogonal silicon braces. An integrated silicon/parylene batch process is introduced to encapsulate these interconnects and achieve high yield. PMID- 17282433 TI - Integrated Vortex Micropumps and Active Micromixers in Polymer Substrates for Automating Bio-fluidic Manipulation. AB - This paper presents a microfluidic mixing module array developed for bio fluid/chemical delivery and mixing. Vortex micropumps, microchannels and pillared surface diaphragm (PSD) active micromixers were successfully integrated into a single polymer-based microfluidic chip, consisting of three mixing modules. The pumping characteristics of the vortex micropump were investigated with both analytical and experimental results. Experiments were also conducted to examine the factors affecting the PSD-based mixing. The integrated mixing module further demonstrated the feasibility of chemical mixing and concentration control. An integrated fluidic system was shown successfully to deliver bio-fluid for real time SPR based detection. A computer-controlled fluid manipulation system is also proposed for the real-time microfluidic operation control. The digitally controllability of the pumping and mixing operations could potentially improve the accuracy and efficiency, and hence, the functionality of the integrated microfluidic system. PMID- 17282434 TI - Theory and Experiments of MEMS Thermal Biosensors. AB - This paper presents a theoretical and experimental investigation of MEMS thermal biosensors in flow-through measurements of metabolites. A model is developed to consider convective heat transfer effects and enzyme kinetics using the Michaelis Menton theory. Numerical solutions from the model are compared with experimental data obtained from a prototype MEMS thermal biosensor. Satisfactory agreement is found between the theoretical and experimental results, indicating that the model is useful for designing MEMS thermal biosensors with optimized performance. PMID- 17282435 TI - Investigation of interactions between two monoclonal antibodies and SARS virus with a Label-free Protein Array. AB - The investigation of interactions between two kinds of monoclonal antibodies and SARS virus with a label-free protein array technique were presented in this paper. The performance consists of three parts: a surface modification for ligand immobilization/surface, a protein array fabrication with an integrated microfluidic system for patterning, packaging and liquid handling, and a protein array reader of imaging ellipsometer. This revealed the technique could be used as an immunoassay for qualitative and quantitative detection as well as kinetic analysis of biomolecule interaction. PMID- 17282436 TI - Experimental Study of Magnetic-based Localization Model for Miniature Medical Device Placed Indwelling Human Body. AB - More and more miniature medical devices (MMD), such as alimentary canal miniature drug delivering device, wireless endoscope, feeding tubes and treatment probes, have been researched and developed for clinical diagnosis and therapy. When a MMD was put into the human body for diagnosis and therapy, it is necessary to provide a non-invasive locating method that can locate the MMD in long-term. Here, a novel magnetic-based position method has been explored. According to the principle of magnet field distribution of magnetic dipole, a special multi-sensor magnetic detecting system has been designed and a modified magnetic position model was proposed based on curve-fitting process with detected data. Models with different coefficient have been compared, and a better one has been constructed. The results demonstrate that the proposed magnetic-based position method is promising and effective. PMID- 17282437 TI - Localizing Retinotopic fMRI Activation in Human Primary Visual Cortex via Dynamic Programming. AB - This paper presents an approach for automatically delineating the borders of human primary visual cortex and finding ridges of maximal response due to static phase-encoding stimuli on fMRI t-statistical maps via dynamic programming. The sensitivity of such an approach to the choice of initial starting and ending points and the identification of the ridge path over a wide response region are addressed. Moreover, retinotopic maps for left and right visual cortex are shown in a population of two normal subjects. PMID- 17282438 TI - Measurements of time characteristics of the gradient magnetic field. AB - Imaging techniques based on the principles of nuclear magnetic resonance (NMR) are modern techniques for the study of chemical, biological and physical properties of substances. The most important are their applications in medical sciences. MR imaging of a specimen weighted with diffusion coefficients requires very accurate data on the time course of the gradient pulse. Diffusion coefficients are determined from the drop of the MR signal measured with and without the application of magnetic field gradients. From the accuracy point of view, the defined course of gradients plays an important role in the computation of coefficients. A minimum rise and fall times, a defined magnitude of the excited gradient of the magnetic field and a symmetry of positive and negative pulses (zero integral of pulses of the same magnitude and opposite polarities) are required. To characterize the time course of gradient pulses or either polarity, simple methods of their measurement has been developed and experimentally tested on a 4.7 T tomograph. The method is based on the principle of instantaneous MR frequency measurements at the presence of a gradient pulse following the excitation of a thin layer situated outside the centre of the gradient field. PMID- 17282439 TI - A New Definition of Mutual Impedance between Two Coils for Simultaneous MRI Signal Reception. AB - A new definition of mutual impedance for two coils used for simultaneous signal reception in MRI is introduced. The new mutual impedances are used to accurately quantify the mutual coupling effect between the two coils so that it can be removed from the measured terminal voltages. Using the new mutual impedances, a new decoupling method can be formulated to obtain the uncoupled voltages. Numerical results on two square coils are obtained and the uncoupled coil voltages calculated based on them indicate extremely small errors when compared with the ideal uncoupled voltages. The new mutual impedances are useful for MRI phased array designs. PMID- 17282440 TI - MRI image intensity correction with extrapolation and smoothing. AB - A class of methods of MR image intensity correction extracts the sensitivity map from the image. This usually causes the edge enhancement artifact in the corrected image. A novel method of extrapolating the image in advance is proposed to reduce this effect significantly. The closest point algorithm is used to perform extrapolation. PMID- 17282441 TI - Improved Radio Frequency Receiver Front-end for Magnetic Resonance Imaging. AB - Based on software radio theory, this paper focuses on researching a direct conversion structure for the radio frequency (RF) receiver front-end and tries to apply this flexible receiver front-end in MRI receiving system. In particular, we look at the conventional architecture of RF receiver front-ends of MRI; present architecture of a direct conversion for RF receiver front-end of MRI; outline the key aspects of designing such multi-channel and multi-mode front-end systems. In addition, based on this architecture, a practical RF front-end receiving system of MRI is given. Two parts are included in this system; one is the conventional receiver front-end the other is the direct conversion design for RF receiver front-end of MRI. PMID- 17282442 TI - Reconstruction of MRI signal losses in EPI images. AB - This paper derives and implements a method for recovering MRI signal losses caused by susceptibility-induced magnetic field gradients (SFGs) in regions with large static field inhomogeneities in echo-planar imaging (EPI). Factor to account for SFGs was added in a traditional EPI equation, which was a simple Fourier transform (FT) for expressing the actual k-space data of an EPI scan. The inverse calculation of this "distorted EPI" equation was used as a kernel to correct reduction in intensity during reconstruction. A step-by-step EPI reconstruction method is proposed to avoid complicated phase unwrapping problems. PMID- 17282443 TI - A method for artifact correction due to demodulation phase errors in magnetic resonance imaging. AB - In the process that MR signal is quadrature demodulated, the initial phases of sinusoid and cosinusoid used as demodulation reference signal exist errors, which results in artifacts in the image. It is typically overcome through precise control of the initial phases with the help of the special hardware, but the errors are not reduced completely. In this work, a method based on reference scan is proposed. Reference scan without frequency encoding gradient and phase encoding gradient is executed before FSE sequence, and an echo train is acquired. The phase errors of sinusoid and cosinusoid that are used to demodulate each echo in the reference echo train are calculated. Then the k-space data of image is corrected by these errors and artifacts are removed. The experiments using 0.35T MRI system demonstrate the effectiveness of this method. PMID- 17282444 TI - Calculation of RF Peak Power for 2D Arbitrary Shape Excitation in MRI. AB - An exact formula has been derived to calculate the required RF (B1) peak power for 2D arbitrary shape excitation in MRI with rectilinear K-space trajectory. An approximate formula has also been derived for spiral trajectory. PMID- 17282445 TI - An efficient non-iterative reconstruction algorithm for parallel MRI with arbitrary k-space trajectories. AB - Parallel imaging using multiple receiver coils has emerged as an effective tool to reduce imaging time in various MRI applications. Although several different image reconstruction methods have been developed and demonstrated to be successful for Cartesian k-space trajectories, there is a lack of efficient reconstruction methods for arbitrary trajectories. In this paper, we formulate the reconstruction problem in k-space and propose a novel image reconstruction method that is fast and effective for arbitrary trajectories. To obtain the desired image, the method reconstructs the Nyquist-sampled k-space data of the image on a uniform Cartesian grid from the undersampled multichannel k-space data on an arbitrary grid, followed by inverse Fourier transform. We demonstrate the effectiveness of the proposed fast algorithm using simulations. In particular, we compare the proposed method with the existing iterative method and show that the former is able to achieve similar image quality to the latter but with reduced computational complexity. PMID- 17282446 TI - Software Compression for Partially Parallel Imaging with Multi-channels. AB - In magnetic resonance imaging, multi-channel phased array coils enjoy a high signal to noise ratio (SNR) and better parallel imaging performance. But with the increase in number of channels, the reconstruction time and requirement for computer memory become inevitable problems. In this work, principle component analysis is applied to reduce the size of data and protect the performance of parallel imaging. Clinical data collected using a 32-channel cardiac coil are used in the experiments. Experimental results show that the proposed method dramatically reduces the processing time without much damage to the reconstructed image. PMID- 17282447 TI - Image-based method for automated phase correction of ghost. AB - One of the most common artifacts for echo planar imaging is the ghost artifact, typically overcome with the aid of a reference scan preceding the actual image acquisition. In this work, we describe an automated free-scan-reference method for reducing ghost artifact using image-based correction. The two dimensional Fourier transformation of an entire data of image matrix is used to reconstruct two new images, one is reconstructed only by even rows, the other is only by odd rows, with the remaining ones zero-filled. Phase shift between even echoes and odd echoes can be computed by using the two images. Unwrapped phase shift gained by Marquardt-Levenber unlinear fitting can be used to suppress the ghost effectively. PMID- 17282448 TI - Cortical Activation during Reading Letter String in Normal and Reverse Directions: An fMRI Study. AB - In order to investigate the difference of cortical activation between reading letter string in normal direction and reverse direction, an fMRI study was conducted. In this study, the cortical activations responsible for Japanese string and Chinese string reading were investigated. The subjects performed normal direction reading task (read strings from left to right), and reverse direction reading task (read strings from right to left). According to the experimental results, the activated brain regions during normal direction reading task and reverse direction reading task were almost the same, besides, we found visuospatial transformation was involved in the reverse direction reading task, while this function was not significant during normal direction reading task. PMID- 17282449 TI - Modeling Time-Intensity Profiles for Pulmonary Nodules in MR Images. AB - Perfusion magnetic resonance imaging (pMRI) is an important tool to assess tumor angiogenesis for the early detection of lung cancer. This paper presents a novel integrated framework for spatio-temporal modeling of pulmonary nodules in pMRI image sequences. After localizing a nodule region in each image, we perform segmentation in the region to extract nodule boundary, and then use thin-plate spline interpolation for nodule registration along the temporal dimension. The resulting spatio-temporal model can lead to many types of nodule characterization. Time intensity profiles of nodules region capture important angiogenic patterns in the lung that can distinguish between cancer and benign nodules and help early detection. PMID- 17282450 TI - Preliminary study of planar RF coils for Magnetic Resonance Microscopy. AB - In this study, we attempt to do a preliminary study of planar RF coils that are aimed for the application of Magnetic Resonance Microscopy (MRM). We will discuss the requirements and considerations for designing such a device. And at last, we conducted a small experiment to show that the design solution we propose is in the correct direction. PMID- 17282451 TI - A fast algorithm to reduce gibbs ringing artifact in MRI. AB - In magnetic resonance imaging, a finite number of k-space data are often collected in order to decrease the acquisition time. The partial k-space data lead to the famous Gibbs ringing artifact with Fourier transform method. The Gegenbauer reconstruction method has been shown to effectively eliminate the Gibbs ringing artifact and restore high resolution. However, the disadvantages of using the Gegenbauer method are more computational time and complicated the choice of parameters. In this paper, we improve the Gegenbauer method by introducing the inverse polynomial reconstruction method and replacing the Gegenbauer polynomials with the Chebyshev polynomials. The new method effectively reduces the reconstructed error and computational cost without any requirement for selection of parameters. Additionally, we present an improved edge detection method which can achieve more accurate edge and make our new reconstruction method more efficient. The proposed method is verified with experiment of the artifact removal. PMID- 17282452 TI - Estimation and Removal of Physiological Noise from Undersampled Multi-slice fMRI data in Image Space. AB - The signal variations induced by respiration and cardiac motion decrease the statistical significance in functional MRI data analysis. Significant components of these fluctuations are aliased into the activation spectrum in standard multi slice imaging protocols. A method of estimation and removal physiological noise in image space is reported. Based on reordering the data from slice ordering to time ordering, the aliased physiological information is available in multi-slice magnitude images. Then physiological noise can be estimated and removed adaptively using signal projecting technique with the actual functional signal preserved. PMID- 17282453 TI - Parallel MRI reconstruction: a filter-bank approach. AB - Parallel magnetic resonance imaging (MRI) using multichannel receiver coils has emerged as an effective tool to reduce imaging time in various MRI applications. However, there are still a number of image reconstruction issues that have not been fully addressed, thereby limited the level of speed enhancement achievable with the technology. This paper reformulates the image reconstruction problem as a digital filter bank problem (in contrast to the conventional matrix formulation used in the popular SENSE technique) and develops an effective algorithm to handle the ill-conditioned problem often encountered in image reconstruction. Simulations based on an eightchannel configuration demonstrate that the proposed method is superior to the SENSE reconstruction especially when large acceleration factors are used. PMID- 17282454 TI - New Algorithm for Extracting Motion Information from PROPELLER Data and Head Motion Correction in T1-Weighted MRI. AB - PROPELLER (Periodically Rotated Overlapping ParallEl Lines with Enhanced Reconstruction) MRI, proposed by J. G. Pipe [1], offers a novel and effective means for compensating motion. For the reconstruction of PROPLLER data, algorithms to reliably and accurately extract inter-strip motion from data in central overlapped area are crucial to motion artifacts suppression. When implemented on T1-weighted MR data, the reconstruction algorithm, with motion estimated by registration based on maximizing correlation energy in frequency domain (CF), produces images with low quality due to the inaccurate estimation of motion. In this paper, a new algorithm is proposed for motion estimation based on the registration by maximizing mutual information in spatial domain (MIS). Furthermore, the optimization process is initialized by CF algorithm, so the algorithm is abbreviated as CF-MIS algorithm in this paper. With phantom and in vivo MR imaging, the CF-MIS algorithm was shown to be of higher accuracy in rotation estimation than CF algorithm. Consequently, the head motion in T1 weighted PROPELLER MRI was better corrected. PMID- 17282455 TI - Preliminary Results from Clinical Application of a Natural Oral Contrast Agent in Magnetic Resonance Imaging (MRI) of the Gastrointestinal (GI) System. AB - A natural magnetic resonance imaging (MRI) contrast based on the pulp of a fruit "Euterpe Olerácea", popularly known as Açai, was investigated. T1 and T2 contrasted images shown the effects of the contrast agent increasing the ability to visualize the contour of segments of the gastrointestinal tract. PMID- 17282456 TI - The Quantitative Assessment of Gd-DTPA in Contrast Enhanced Magnetic Resonance Angiography. AB - Recently, the use of MRI contrast agents has been proven to be substantially improved sensitivity and specificity in many clinical applications. CE-MRA has higher blood signal based on the T1 and T2-shortening property of contrast agents, so that even the small vessels can be visualized. The use of contrast agents can improve lesion detection and characterization. The routinely used dose of contrast agents in the routine MRI examinations only relies on the weight of the subject. The purpose of this study is to obtain the clinically optimal dose for 3D-TOF (time-of-flight) pulse sequences for CE-MRA examinations. In the phantom study, ten test tubes were filled with saline mixed with different dose of Gd-DTPA. It is found that the optimal dose of Gd-DTPA for saline phantom by using 3D-TOF pulse sequences is 20 mM. Also, there has no differences of optimal doses between Omniscan and Magnivist contrast agents Gd-DTPA. The results show that consistent high quality CE-MRA images might be obtained by using 0.25M Gd DTPA (half of the routine dose) with 3~4 cc/sec injection rate for all clinical cases. The benefits of this study might be to minimize dose and potential toxicity. Additionally, the decrease of the cost of contrast agents might be achieved. It is expected to provide the recommended dose of Gd-DTPA for contrast enhanced MRA in clinical routine diagnosis. PMID- 17282457 TI - A new serial image registration method for contrast-enhanced MRI study. AB - This paper presents a new method for aligning serial images acquired in contrast enhanced MRI studies. A unique feature of the proposed method is that it uses dynamic references, rather than a single reference image as in the conventional method, to obtain co-registration of serial images. Specifically, each image serves as a reference for its neighboring images and the overall registration of all serial images is derived subsequently. We tested the new method using a digital image phantom and in-vivo contrast-enhanced tumor MRI data, using a least square registration criterion and a rigid-body spatial transformation. Preliminary results showed that the new method is generally more robust and accurate than the conventional method. PMID- 17282458 TI - Metabolite concentrations of healthy mouse brain by Magnetic Resonance Spectroscopy at 7 Tesla. AB - In vivo1H short echo-time Magnetic Resonance spectra are made up of overlapping spectral components from many metabolites. Typically, they exibit low signal-to-noise ratio. Metabolite concentrations are obtained by quantitating such spectra. Quantitation is difficult due to the superposition of metabolite resonances, macromolecules, lipids and water residue contributions. A fitting algorithm invoking extensive prior knowledge is needed. We quantitated1H in vivo mouse brain spectra obtained at 7 Tesla using the time-domain QUEST method combined with in vitro metabolite basis set signals. Brain metabolite concentrations estimated from eight mouse brain signals are compared to previously reported results. PMID- 17282460 TI - Model implementation and case study for the lossy, multilayered spherical head phantom in MRI application. AB - To better simulate RF field behavior in the human head for MRI applications, dyadic Green's function (DGF)/method of moment (DGF/MOM) -based solutions of the electromagnetic field (EMFs) inside a head-sized, stratified sphere in different MRI coils are presented. The lossy, multilayered spherical head phantom has similar radial conductivity and permeability profiles as human head and is loaded in MRI surface and RF volume coils. B1 field pattern, SAR distribution, flip angle, signal intensity (SI), and other MRI image parameters are calculated in this study. The results reported herein show the operating characteristics of the field/tissue interactions and safety properties for human head model in different coils. PMID- 17282461 TI - Construction of Optimal Velocity Encoding for Cerebral Blood Flow Volume Measurement with Phase-Contrast MRA. AB - PURPOSE: Accurate velocity encoding is crucial for quantification of arterial inflow and venous outflow in intracranial diseases. The purpose of this study was to optimize the velocity encoding of phase-contrast (PC) MRA and quantify cerebral blood flow in normal volunteers. METHODS: Ten healthy volunteers were examined on a GE 1.5T MR system with 2D PCMRA sequence. The parameters of the sequence were as follows: TR 40ms, TE 6.6ms, flip angle 20°, slice thickness 4mm, matrix 256x256, field of view 140 mm. In each cardiac cycle, 40 images were obtained. Velocity encoding was set from 30 to 90 cm/sec at 10cm/sec interval for total of 7 scans per volunteer. The scan level was chosen at C2 perpendicular to the vessels of interest. Data were analyzed using CV Flow software on a GE Advantage Windows Workstation. PMID- 17282459 TI - Accuracy of noninvasive quantification of brain NAA concentrations using PRESS sequence: verification in a swine model with external standard. AB - The metabolite ratios had been employed in the field of MR spectroscopy (MRS) for a long period. The main drawback of metabolite ratio is that ratio results are not comparable with absolute metabolite concentration in vivo. The purpose of this study was to examine the accuracy of noninvasive quantification of brain N acetylaspartate (NAA) concentrations using previously reported MR external standard method. Eight swine were scanned on a GE 1.5 T scanner with a standard head coil. The external standard method was utilized with a sphere filled with NAA, GABA, glutamine, glutamate, creatine, choline chloride, and myo-inositol. The position resolved spectroscopy (PRESS) sequence was used with TE=135 msec, TR=1500 msec, and 128 scan averages. The analysis of MRS was done with SAGE/IDL program. In vivo NAA concentration was obtained using the equation S=N * e( TE/T2) * [1-e(-TR/T1). In vitro NAA concentration was measured by high performance liquid chromatography (HPLC). In the MRS group, the mean concentration of NAA was 10.03 plusmn 0.74 mmol/kg. In the HPLC group, the mean concentration of NAA was 9.22 plusmn 0.55 mmol/kg. There was no significant difference between the two groups (p = 0.46). However, slightly higher value was observed in the MRS group (7/8 swine), compared with HPLC group. The range of differences was between 0.02~2.05 mmol/kg. MRS external reference method could be more accurate than internal reference method. 1H MRS does not distinguish between N-acetyl resonance frequencies and other N-acetylated amino acids. PMID- 17282462 TI - Monte carlo method study of terahertz pulse propagation in biological tissue. AB - The terahertz pulse (THz pulse) propagation in biological tissue is simulated by Monte Carlo method (MCM). The migratory route of THz pulse in the tissue is presented. The computation model is based on the assumption that the refraction indexes of tissue and air are mismatch and both surfaces of the tissue have the reflection effect for THz pulse. PMID- 17282463 TI - Treatment of ill-balanced datasets of fMRI with Modified Fuzzy c-means Method. AB - In fMRI dataset, the population of actived voxels is always much less than the total population of the voxels, and that produced an ill-balanced dataset. Some methods, such as limiting the analysis to the gray matter voxels where the BOLD signal is expected and removing the voxels that is absolutely non-actived based on statistical criteria, have been used to treat the ill-balanced dataset. In this article, a new method, Modified Fuzzy c-means(MFc), has been proposed to treat the ill-balanced dataset of fMRI. The main difference from other statistical methods is that it is datadriven. iven. The MFc method is used to classify the voxels into two clusters with nearly the same population and all actived voxels are contained in one cluster. Thus we got nearly half voxels to analysis and the ill-balanced dataset can be treated. The efficiency of clustering analysis is also boosted. PMID- 17282464 TI - A Deconvolution Approach Based on Multi-Tensor Model to Solve Fiber Crossing in Diffusion-MRI. AB - A deconvolution approach, based on a multi-tensor model, is presented to solve fiber crossing in diffusion MRI. In order to provide a direct physical interpretation of the signal generation process, we re-wrote the classical multi tensor model, identifying a significant scalar parameter alpha to characterize the deconvolution process. Simulations show that, in presence of noise, the method is able to correctly separate fiber crossing. Application on in-vivo data highlights the ability of our approach to distinguish more than two fibers within the same voxel, suggesting its application in fiber tracking or connectivity studies even of complex brain structures. PMID- 17282465 TI - Improved partial k-space reconstruction technique for dynamic myocardial perfusion MRI. AB - The advent of partially parallel k-space data acquisition and reconstruction techniques has resulted in a drastic reduction in acquisition time. In this work, we have shown that the use of a new hybrid technique for reconstruction of partial k-space data can reduce acquisition time without loss of spatiotemporal resolution. The technique is termed hybrid k-t GRAPPA since it is a combination of k-t GRAPPA and an image-k-space keyhole technique. The hybrid method with an acceleration factor 4 generated better results than standard GRAPPA with acceleration factor 2 in preliminary results. PMID- 17282466 TI - Extraction of brain vessels from magnetic resonance angiographic images: concise literature review, challenges, and proposals. AB - The automated extraction of brain vessels from magnetic resonance angiography (MRA) has found its applications in vascular disease diagnosis, endovascular operation and neurosurgical planning. In this paper we first present a concise technical review on cerebral vasculature extraction from MRA. It reveals the latest development in the area of vessel extraction. Then we detail the main challenges to the researchers working in the vessel extraction and segmentation area. Based on the review and our experience in the area, we finally present our proposals on ways of developing robust vessel extracting algorithm. Examples of brain vasculature extracted with advanced hybrid approach are shown. Twenty one references are given. PMID- 17282467 TI - MRA Images Identification of the Artery Blood Vessel of the Knee with SOM LVQ Neural Networks as Auxiliary. AB - The ways of angiography are divided into two kinds at present: the invasive type and the non invasive type. Because the magnetic resonance angiography (MRA) has advantages of the non invasive type, thus people can accept MRA more easily. Presently, to diagnoses for the initial stage triage of the blood vessel on clinic by MRA mostly. We to be allowed to see clearly that the shape of lower limb artery which like the dendrite and the blood vessel is thick from the trunk to the thin branch, also we can see the narrow embolism and the blocked place through MRA. This study is aiming at the image of artery of blood vessel by MRA assay, and is attempting to use two-dimensional structure of SOM and LVQ to make out topologies for the shape of artery of blood vessel. We expect that MRA could be useful tools for earlier on the quick triage and auxiliary diagnosis of doctors. By actual examples truly prove that patients after peripheral arterial occlusive disease (PAOD) treatment can diagnose effectively, shorten the time of patients waiting for reports and improve the whole efficiency of the medical treatment system. PMID- 17282468 TI - 3-dimensional brain source imaging by means of laplacian weighted minimum norm estimate in a realistic geometry head model. AB - We investigated the source localization performance of the Laplacian weighted minimum norm (LWMN) estimate technique in a realistic geometry (RG) head model in the present study. We simulated current sources at different brain regions with various noise levels. The present results show there is no obvious depth dependency on the three-dimensional (3D) source estimation. The average source localization error over all simulated cases is about 10 mm. The tangential sources exhibit larger localization errors than the radial sources when they are close to the epicortical surface. The localization error will increase when the noise level increases. The LWMN technique was applied to source imaging of motor potentials induced by finger movement in a human subject. Both activities in the motor and premotor cortex, which are related to the execution and coordinating of the finger movement, were reconstructed by the LWMN technique. The present study suggests that LWMN has great ability in 3D sources imaging. PMID- 17282469 TI - Integrating parallel imaging with generalized series for accelerated dynamic imaging. AB - One key problem in MR dynamic imaging (e.g. dynamic contrast-enhanced (DCE) imaging of breast cancer) is low spatiotemporal resolution. To tackle this problem, this paper presents a novel method to integrate parallel imaging using multiple receiver coils with generalized series (GS) imaging. The proposed method takes advantage of both the conventional parallel data acquisition scheme and the GS model-based imaging method to achieve higher spatiotemporal resolution in dynamic imaging. Simulations on human breast cancer imaging and mammary tumor imaging of rat and the experiment on DCE imaging of human chest tumors yielded excellent results by the proposed method. PMID- 17282470 TI - Quenching Properties of a Self-Referenced Fluorescence Oxygen Nanosensor under a Wide-Field Intrinsic Optical Signal Imaging System. AB - Wide-field intrinsic optical signal (IOS) imaging is an excellent method to map in vivo neurological metabolic changes during brain activity. It has a spatial resolution of 50-100μm and a wide imaging field of several cm2that cannot be achieved by regular microscopic imaging. A nano encapsulated fluorescence dye sensor that is specifically sensitive to oxygen level was fabricated by using electrostatic layer-by-layer (LbL) self-assembly technique. Fluorescence images of the nanosensor solution were collected by a wide-field IOS imaging system under different oxygen concentrations. Mathematical models for nanosensor fluorescence were developed based on the imaging results. Correlations between the nanosensor fluorescence and oxygen concentration models indicate an inverse quenching relationship between the nanosensor fluorescence and oxygen concentration. PMID- 17282471 TI - Whole-body Fluorescent Optical Imaging Based on Power Light Emitting Diode. AB - With complex configuration, the general whole-body fluorescence optical imaging system is power-consuming for it is mainly composed of laser or mercury lamp, filter and fiber-optic cable. In this paper we aimed at setting up a compact imaging system based on power light emitting diode (LED). We first discussed fluorescence excitation efficiency of mercury lamp and LED. Then we developed a compact prototype whole-body fluorescence optical imaging system based on power LED. With the prototype, we monitored the dynamic course of green fluorescence protein (GFP) expressing tumors in the same intact nude mice. We also recorded the temporal behavior of the infectious process of GFP-expressing bacteria from outside intact infected animals. This study puts forward a platform for monitoring tumor growth. The experiment reveals that it is doable to substitute power LED for mercury lamp for whole-body fluorescence optical imaging. PMID- 17282472 TI - Using running subtraction to detect the wavefront of cortical spreading depression. AB - The purpose of this paper was to present a simple method for analyzing the optical images from cortical spreading depression (CSD). The experimental data was acquired by optical intrinsic signal imaging (OISI) in Sprague-Dawley rats. In order to characterize the spatiotemporal evolution of CSD, especially the wavefront, running subtraction and background subtraction were both applied to process the series of images. By comparing the output results of the two different methods, running subtraction was more sensitive to the first transient and small phase of CSD (i.e. wavefront), and the extracted spatial pattern of CSD showed less vascular artifacts. For these advantages, running subtraction proved to be an appropriate approach to detect the wavefront of CSD. PMID- 17282473 TI - In vivo Optical Spectroscopy of Acoustically Induced Blood Stasis. AB - Ultrasound-induced blood stasis has been observed for more than thirty years. Most of the literature has been focused on the health risks associated with this phenomenon and methods employed to prevent stasis from occurring during ultrasound imaging. To date, experimental observations have been either in vitro or invasive. The current work demonstrates ultrasound- induced blood stasis in murine tumor and nontumor tissue, observed through noninvasive measurements of optical spectroscopy, and discusses possible diagnostic uses for this previously undesirable effect of ultrasound. PMID- 17282474 TI - Detection and identification of Colon Cancer and Rectum Cancer Using Fluorescence and Raman Spectrum. AB - Laser-induced fluorescence spectroscopy (LIF) and Raman spectrum of serum for detection of colon cancer and rectum cancer were investigated in this paper. The aim of this study was that using Raman spectrum and LIF analysis the serum of colon cancer and rectum cancer for found the difference compared to normal, the difference was found. For example: the peaks intensity and red shift both different In this paper, we investigated 82 colon cancers, 69 rectum cancers and obtained 80.7%, 82.5% accuracy separately compared to clinical diagnostic. It is exploding that use Raman spectrum and LIF to detection of cancer. PMID- 17282476 TI - An integrated system for medical diagnosis of human facial perception. AB - We present an integrated system for medical diagnosis of the human facial perception in human brain. The human facial perception is an important function in the human visual system. The diagnosis of the human facial perception is an important issue to be tackled in the medical field because some neurological diseases including the autism are supposed to be caused by un-ordinal behavior of the human facial perception. The behavior can be observed through electro magnetophysiology tests using test images. However, the generation of the test images is tedious work because various types of test images are needed to perform the tests. The system automates the process of the test image generation. The system also has an integrated database to manage various types of experimental data. They are test image data, image filtering parameters, time-varying signal data gotten by medical equipments, and other experimental information. The system stores the data in an integrated database to make the tests easy. We evaluated the system in corporation with medical researchers. The implementation and evaluation of the system are explained in this paper. PMID- 17282475 TI - The Effect of Auditory Stimulation upon Cerebral Blood Oxygenation in Infants: Measurements by Light Emitting Diode (LED) Near Infrared Spectroscopy. AB - This study assessed the feasibility of neonatal cerebral oxygen monitoring by near-infrared light spectroscopy (NIRS) using a light emitting diode (LED) based system. We aimed to measure the changes in cerebral oxygen saturation, as regional oxygen saturation and tissue oxygenation index, in response to auditory stimuli. Documenting changes in oxygenation in response to such stimuli will help validate the usefulness of LED-NIRS as a tool in the study of cerebral oxygen saturation in neonates. PMID- 17282477 TI - Laser Reflectance Imaging of Curved Tissue-equivalent Phantoms. AB - The surface backscattered radiations of curved tissue-equivalent phantom are measured using miniature multi-probe laser reflectometer imaging system. Phantom models are prepared using paraffin wax mixed with wax colors and their optical parameters are determined by comparing measured backscattered profile with that of Monte Carlo Simulation procedure. Abnormalities with optical parameters 5% less than the normal phantom are introduced at various depths in different locations. These phantoms are scanned using miniature laser reflectometer scanner. The acquired data after digitizing, interpolation and filtering is represented as 3-D color coded images which show the location and size of the abnormalities. PMID- 17282478 TI - The development of small laboratory animal atlas. AB - A new cryosection milling imaging system with high spatial resolution is developed to screen small laboratory animals such as mice and rats. The system hardware consists of cutting device, Image Capture and Photography device, refrigerated storage and parallel data processing system. By this system high spatial resolution (no less than 20 μm) small laboratory animal atlas can be achieved. After image registration, image segmentation and 3D reconstruction, a small laboratory animal can be visualized. This paper, taking an adult SD (Sprague-Dawley) rat as an example, describes an experimental process of cryoection milling imaging, in which SD Rat atlas was obtained(the voxels size is 20 μm × 20 μm × 20 μm, cryosection images were captured in 4,600×2,580×24-bit BMP format, 9475 pages, 314.68G). By this system 3D microstructure of small laboratory animal can be obtained accurately. Cryoection milling imaging system offers a new efficient method for small laboratory animal study. PMID- 17282479 TI - A fast reconstruction algorithm for fluorescence diffusion optical tomography. AB - Fluorescence Optical Diffusion Tomography (FODT) is considered as one of the most promising ways for non-invasive molecular-based imaging. Many reconstructed approaches to FODT utilize iterative methods for data inversion. However, they are regarded as being time-consuming and far from meeting the real-time imaging requests. In this work, a fast pre-iteration algorithm based on the generalized inverse is established, which divides the image reconstruction into two steps that are off-line pre-iteration and on-line one-step reconstruction. In the pre iteration step for obtaining the approximation of generalized inverse, a second order iterative format is employed to accelerate the convergence. Simulation based on the linear diffusion model shows that the distribution of fluorescent yield can be well estimated by this algorithm with second-order iteration. And the reconstructed speed is remarkably increased. Time-efficiency of this method will potentially promote the development of real-time imaging and the dynamic monitoring of molecular activity. PMID- 17282480 TI - Automated classification schemes for optical tomographic arthritis scans. AB - We have recently developed a sagittal laser optical tomographic (SLOT) imaging system for the diagnosis and monitoring of inflammatory processes in proximal interphalangeal (PIP) joints of patients with rheumatoid arthritis (RA). While cross sectional images of distribution of optical properties can now be generated easily, clinical interpretation of these images remains a challenge. In this paper, we apply and analyse two machine learning methods for optimal identification and severity classification of RA in a data set of 78 joints. The methods surveyed include Fisher Face with Support Vector Machines (SVMs), and Transformed Mixtures of Gausians (TMG). It appears that TMG methods outperform the approach using Fisher Face with SVMs; however, the results need to be further validated in studies involving larger patient populations. PMID- 17282481 TI - Cerebral hemodynamic reactivity measured by near-infrared spectroscopy in migraineurs. AB - Brain hemodynamic responses (BHR) of healthy subjects and migraineurs performing a breath holding task are measured by functional near-infrared spectroscopy (fNIRS) method. The response curves are deconvolved from a rectangular input function to yield the impulse response (IR) function of BHR which was then modeled by a summation of three gaussians. Our results show that the amplitude coef£cients estimated from IR of BHRs are approximately 350% and the dispersion coef£cients 145% higher for healthy subjects. These results con£rm the £ndings of several other researchers where a decrease in cerebral blood ¤ow has been shown for migraineurs during breath holding tasks. PMID- 17282482 TI - Electrical impedance tomography based on sensitivity theorem with singular value decomposition. AB - In electrical impedance tomography (EIT), distribution of internal resistivity of an unknown object is estimated using measured boundary voltage induced by different current patterns. In this paper singular value decomposition is modified with a threshold to be used in the sensitivity theorem for reconstruction of EIT images. Two different parameters are added to the singular values according to a threshold. The method has a major impact on efficient solution of EIT to achieve improved image resolution. Computer simulation and experiments indicate that this method performs better than the previous truncated SVD without using the threshold in terms of reconstructed image resolution. PMID- 17282483 TI - High precision Multifrequency Electrical Impedance Tomography System and Preliminary imaging results on saline tank. AB - To establish a high precision data acquisition system for multi-frequency electrical impedance tomography (EIT), a series of methods were introduced. Those methods include building a driving signal with up to four frequency components to diminish the effect of the dynamic change of tissues resistivity, extracting the impedance information by a digital demodulator that can improve the SNR by 8 times. The system that established can work at a wide range from 1.6kHz to 380kHz. Its CMRR is 74dB at 100kHz. The output impedance of current source is 2MΩ at that frequency. And measurement precision on a 100ohm resistor is better than -80dB in full bandwidth. Both the quasi-static and the dynamic imaging results based on a saline tank can reflect the resistivity changes inside the phantom clearly. Therefore, the system was competent in multifrequency EIT research work. PMID- 17282484 TI - UWB Microwave Imaging for Breast Tumor Detection in Inhomogeneous Tissue. AB - Inhomogeneous breast tissue has a strong scattering effect when the breast is illuminated by a detecting signal. This effect influences the tumor's response signal and makes the imaging result worse. This paper presents an efficient imaging approach to detect breast tumor in inhomogeneous tissue. We separated the transmitter and receiver to lower the rigorous request for antenna design. An ultra wideband microwave pulse was transmitted into the breast and the backscatter signal was received by each antenna in an array. The transmitter was set at four different locations sequently and four-group backscatter data were received and added together as the response signal from the tumor. Results of signal processing demonstrate that this method is superior to the previous methods and can localize the tumor efficiently. PMID- 17282485 TI - An image monitoring system for intraperitoneal bleeding using electrical impedance tomography and its preliminary results in vivo. AB - An image monitoring system using electrical impedance tomography (EIT) for intraperitoneal bleeding was designed (FMMU V3.5). It consists of a constant current driving source with frequency of 50 KHz, a high accuracy measurement module, a driving and measuring mode program-controlled circuits, a data acquisition card, an optoelectronic isolated digital I/O board, and a custom specified linear power supply units. The system applied equal-potential back projection algorithm to reconstruct dynamic images. The relative accuracy of the system is 0.1%, the RTI noise is 11.1 mu V (bandwidth 100 Hz). Based on physical phantom, images reconstructed by the system showed that it can image dynamically to the infused saline solution, and by infusing more solution the gray changed area of the image also enlarged accordingly. For stomach filling model in vivo, the dynamic imaging processes showed that the system can clearly and sensitively monitoring the saline solution drinking into the stomach for 50 ml each time, and by drinking more saline solution the conductivity changed area of the dynamic image also enlarged accordingly. PMID- 17282486 TI - Primary Multi-frequency Data Analyze in Electrical Impedance Scanning. AB - This paper deduced the Cole-Cole arc equation in form of admittance by the traditional Cole-Cole equation in form of impedance. Comparing to the latter, the former is more adaptive to the electrical impedance scanning which using lower frequency region. When using our own electrical impedance scanning device at 50 5000Hz, the measurement data separated on the arc of the former, while collected near the direct current resistor on the arc of the latter. The four parameters of the former can be evaluated by the least square method. The frequency of the imaginary part of admittance reaching maximum can be calculated by the Cole-Cole parameters. In conclusion, the Cole-Cole arc in form of admittance is more effective to multi-frequency data analyze at lower frequency region, like EIS. PMID- 17282487 TI - Localization of Target Structures through Data Fusion Applied to Neurostimulation. AB - Symptoms of Parkinson's Disease can be relieved by Deep Brain Stimulation (DBS), which is based on an accurate positionning of electrodes in specific structures of the Basal Ganglia, e.g. the SubThalamic Nucleus (STN) and the Internal Globus Pallidus (GPi), and of the thalamus. We planned to develop an automatized method for the identification of these structures, deeply located in the brain, through data fusion. Information, provided by both anatomical MR images and expert knowledge, was managed in a possibilist frame by a fuzzy logic approach. A multi scale graph-based virtual atlas, modeling the theoretical anatomical knowledge, was matched to each patient's data (MRI), in order to compute an estimation of the structures' location,thus assisting the physician in the definition of the target. The method has been tested on several images with promising results. In the long run, it might open opportunities to a fully automatized surgical planning. PMID- 17282488 TI - EEG source estimation method considering the shape of the cortical surface. AB - The precision of current source estimation of electroencephalography by referring the shape of the brain acquired as MRI was considered. The location of the candidate current dipoles was limited to on the surface of the cortex, and the orientation was constrained to the vertical to the surface. Electric stimulation of median nerve was executed to confirm whether it works appropriately by checking the estimated active area on the cortex. PMID- 17282489 TI - Edge element method for magnetic induction tomography. AB - A formulation for the solution of the 3D eddy current problem is presented with the edge element method. The method can minimize the computation time of 3D nodal finite element method in terms of potential and eliminate spurious modes resulting from solving magnetic field directly. Theoretical analysis and numerical modeling of saline-filled tank system demonstrate the accuracy of this method. The powerful method can be considered an important step towards the inverse problem of MIT and used to research on the spatial resolution, choice of the best operation frequency and the reconstruction of conductivity imaging of MIT. PMID- 17282490 TI - Multivariate coherence decomposition: a simulation study. AB - This paper presented a method, termed MVCCDFD(Multivariate coherence decomposition), for mapping coherent brain sources at given frequencies. By calculating averaged coherence over all pairs of channels, we can know at which frequencies there are strong coherence. And then, by utilizing MVCCDFDto corresponding frequencies we can get the 2D distributions of coherent sources at given frequencies. Computer Simulation shows that this method can identify the coherent brain sources at different frequencies. PMID- 17282491 TI - Energy Transform and Initial Acoustic Pressure Distribution in Microwave-induced Thermoacoustic Tomography. AB - A study of Microwave-induced Thermoacoustic Tomography is presented in this paper. Microwaves illuminate biological tissues to generate acoustic waves by thermoelastic expansion when electromagnetic energy was absorbed by human tissues. The generated acoustic waves carry information about different electromagnetic properties of different tissues which will be collected and processed to reconstruct human cross section image. In this paper, digital electromagnetic human body model with 1cm resolution was founded according to algorithm requirements. Firstly we analyzed the transform and interrelation among electromagnetic energy, heat energy and acoustic energy. On the basis of established human model: (1) we calculated initial acoustic pressure distribution in cross section image under plane microwave radiation with different frequency. It shows that microwave absorption properties and initial acoustic pressure were different with the change of frequency; (2) using single pulse to illuminate human model, initial acoustic pressure maps of thorax cross section at different time steps were analyzed. These results provided a research basis for further study and calculation of acoustic pressure in microwave-induced thermoacoustic tomography. PMID- 17282492 TI - An optimizing design method for electrode structure parameter of electrical impedance tomography. PMID- 17282493 TI - Analysis of Electric Field in Real Rat Head Model during Transcranial Magnetic Stimulation. AB - Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses the principle of electromagnetic induction to generate currents in the brain via pulsed magnetic fields. Although there are some researches about electric field and current density distribution induced by TMS on human brain, similar analyses on other species are rarely known. TMS is often used on rat models before used on human being, then how TMS affects the rat brain is critical information for researchers. In this paper, a real rat head model during transcranial magnetic stimulation is presented. 3D-reconstruction method and finite element method are carried out to calculate the spatial distribution of the electric field. This model is quite useful to design TMS experiments on rats and interpret these results. PMID- 17282494 TI - Bioenergy based Medical Diagnostic Application based on Gas Discharge Visualization. AB - Allopathic medical diagnostic divides the human body into physiological and organ systems and analyzes the condition of these systems individually based on their anatomy, physiology, biochemistry and pathology. However, without analysis of intricate signals between these systems, it is difficult to provide a deeper insight of a patient's health, therefore reliable detection of diseases. This purpose of this paper is to demonstrate the possibilities of providing holistic medical screening through measurement of bioenergy fields which have both biophysical and biophysic bearings. PMID- 17282495 TI - Detecting human head conductivity distribution using one component magnetic flux density. AB - We propose a novel Magnetic Resonance Electrical Impedance Tomography (MREIT) algorithm, RBF-MREIT algorithm and apply it to reconstruct the conductivity distribution of human head. Computer simulations are conducted on a three-sphere head model to test the feasibility of the proposed algorithm. The simulation results demonstrate that the RBF-MREIT algorithm can estimate the conductivity values within the head using only one component of the magnetic flux density. PMID- 17282496 TI - A finite difference method for solving the three-dimensional EEG forward problem. AB - A finite difference method (FDM) has been implemented to solve the electroencephalogram (EEG) forward problem. This method has been evaluated by means of computer simulations, by comparing with analytic solutions in a three sphere concentric head model. The effects of dipole eccentricity, spacing of finite difference model and number of grid nodes on solution accuracy are also addressed in the simulations. The simulation results suggest that the FDM can achieve satisfactory forward solution due to a dipole source. PMID- 17282497 TI - Investigation of human interpretation process based on eyetrack features of biosignal visual inspection. AB - Although well standardized, the human interpretation of biosignals highly depends on the observer experience and personal skills. In this paper, a new eyetrack based approach is proposed for quantitative assessment of these important factors. The visual experiment carried out on cardiologists of various professional experience supplied the scanpaths data for the analysis in context of observed ECG traces. Selected parameters of the cardiologist eye trajectory were particularly correlating with the declared proficiency and the recording complexity, and thus may be interesting as an objective assessment tool for the professional staff survey. The paper proposes also a focus attention-based analysis of the human interpretation procedure and its evolution with the growth of experience. The proposed approach, without the verbalization necessity, allows the cardiologists know-how to be extracted, analyzed and implemented in the automatic interpretation algorithm for better emulate the human way of thinking. PMID- 17282498 TI - A new Image Reconstruction Algorithm for Magnetic Resonance Electrical Impedance Tomography Using one Component of Measured Magnetic Field. AB - In this paper, a new conductivity images reconstruction algorithm for Magnetic Resonance Electrical Impedance Tomography (MR-EIT) is proposed. The algorithm doesn't need to rotate mechanically the imaged object and can image the conductivity distribution of object at oblique slice. The proposed reconstruction algorithm in this paper is more applicable than other MR-EIT reconstruction algorithms using one component of magnetic flux density. It is not necessary that the main magnetic field is perpendicular to the imaging slice, and so can be used for permanent MRI scanners as well as superconductive MRI scanners. PMID- 17282499 TI - The Application of Multi-look in UWB Microwave Imaging for Early Breast Cancer Detection Using Hemispherical Breast Model. AB - In UWB microwave imaging for early breast cancer detection, energy allocation to each tumor may be unequally when using single-look method, thus some of the targets may not be detected when multi-tumors exist. In this paper, we put forward a multi-look method: the source was set at eight difference places and eight groups of back-scattered signals were achieved by receiving antennas, the signals of each group were processed and results were added together. Theoretical analysis and numerical simulation show that multi-look method can not only reduce the clutters in imaging results but also detect all tumors more efficiently, and it is better than single-look method. PMID- 17282500 TI - A novel approach to design weight matrix of Hopfield network. AB - The sum of outer product learning rule is a traditional method to generate the weight matrix of Hopfield network. It requires all of the samples to be pairwise orthogonal, which is difficult to achieve in general conditions. In this paper, a novel approach to design the weight matrix is proposed, and it just requires samples to be linearly independent that is easy to carry out. As we all know, a group of linearly independent vectors can be transferred to a group of standard orthogonal vectors. Thus, we can construct weight matrix W using these standard orthogonal vectors instead of original samples. Experimental results demonstrate that the new approach can help to achieve an ideal auto-association performance. PMID- 17282501 TI - SVM for Solving Forward Problems of EIT. AB - Support Vector Machine (SVM) can be seen as a new machine learning way which is based on the idea of VC dimensions and the principle of structural risk minimization rather than empirical risk minimization. SVM can be used for classification and regression. Support Vector Regression (SVR) is a very important branch of Support Vector Machine. Partial Differential Equations (PDEs) have been successfully treated by using SVR in previous works. The forward problems of EIT are the basis of EIT inverse problems. The forward problem's essence is to solve PDEs. The method has been successfully tested on the forward problems of EIT and has yielded accurate results. PMID- 17282502 TI - Using fractal analysis to characterize cerebral blood flow and immunohistopathology for ischemic stroke research. AB - This paper presents an application of fractal analysis to characterization of global cerebral blood flow and immunohistopathology for ischemic stroke research on animal experiments. A brain's vasculature has features of a branching tree and can be modeled as a fractal system. Fractal analysis can be then employed to assess cerebral blood flow and immuno-positives on a whole brain section. Fractal analysis on experimental data from three imaging modalities under ischemic and control status is presented in this paper. Statistic analysis and correlative study prove the effectiveness of fractal analysis. An analytical description of fractal parameters for experimental ischemic stroke has been achieved. PMID- 17282504 TI - Hip Prosthesis Detection based on Complex Natural Resonances. AB - Resonance based radar target detection has been applied to Ground Penetrating Radar (GPR) applications for the detection and recognition of landmines. Target detection is achieved by searching for certain target dependent Complex Natural Resonances (CNRs), which could be considered as a feature set for identification. In this paper, detection of a hip prosthesis under human tissues using resonance based target detection technique is investigated. PMID- 17282503 TI - A texture classification method for diffused liver diseases using Gabor wavelets. AB - We proposed an efficient method for classification of diffused liver diseases based on Gabor wavelet. It is well known that Gabor wavelets attain maximum joint space-frequency resolution which is highly significant in the process of texture extraction and presentation. This property has been explored here as the proposed method outperforms the classification rate obtained by using dyadic wavelets and methods based on statistical properties of textures. The feature vector is relatively small compared to other methods. This has a significant impact on the speed of retrieval process. In addition, the proposed algorithm is not sensitive to shift of the image contents. Since shifting the contents of an image will cause a circular shift of the Gabor filter coefficients in each sub-band. The proposed algorithm applied to discriminate ultrasonic liver images into three disease states that are normal liver, liver hepatitis and cirrhosis. In our experiment 45 liver sample images from each three disease states which already proven by needle biopsy were used. We achieved the sensitivity 85% in the distinction between normal and hepatitis liver images and 86% in the distinction between normal and cirrhosis liver images. Based on our experiments, the Gabor wavelet is more appropriate than dyadic wavelets and statistical based methods for texture classification as it leads to higher classification accuracy. PMID- 17282505 TI - A fast method to derive realistic FEM models based on BEM models. AB - A fast method for constructing a FEM head model based on the relevant BEM head model is presented. The method has been evaluated and shown to provide an alternative means of deriving FEM head models. The availability of such fast method would facilitate the realistic head modeling for EEG/MEG research. PMID- 17282506 TI - Cardiac motion analysis using nonlinear biomechanical constraints. AB - Quantitative assessment of the motion and deformation variability of the heart has important implications for the understanding, diagnosis, and treatment of cardiac diseases. Various existing image-based approaches typically rely on linear constraining models which are however physically implausible. In this paper, we present a biomechnically constrained framework for the estimation of left ventricle deformation from medical image sequences using more realistic nonlinear geometry and material models. Once the myocardial boundaries and the sparse corresponding boundary points are derived from an active region model, we construct the cardiac dynamics where the left ventricle is modelled as an Mooney Rivlin material undergoing large deformation. We then rely on the Newmark scheme to perform frame-to-frame estimation of the cardiac motion/deformation parameters. Experiments have been performed with 3D cardiac MR image sequences with very encouraging results. PMID- 17282507 TI - Left ventricular systolic dysfunction identification by motion analysis. AB - This paper presents a new technique for identification of regional dysfunctions in the left ventricle from 2-D echocardiography. It uses a novel left ventricular border tracking algorithm based on Fuzzy inference system. In this paper we show how the regional dysfunction present in the left ventricle can be identified by tracking the movement of centre of mass of left ventricle in a 2D space. The path pattern of that point traced over the cardiac cycles shows variation between the two groups. The main advantage of this proposed approach is the smaller date handling in regional dysfunction identifications unlike other existing methods. The method is illustrated on the real 2D echocardiograph dataset that includes patients having dysfunctions in the left ventricular wall. The diagnostic potential of this method is explained in detail. PMID- 17282509 TI - Digitization and synchronization method for electrocardiogram printouts. AB - A method of digitization and synchronization of ECG signals for use in vectorcardiography is hereby presented. It is intended to allow the computerized use of the ECG printout used by most cardiologists. The problem is solved by digitizing the printout, which can then be used for vectorcardiography and other modern techniques, once it is synchronized using cross-correlation. Cross correlation was found to be a superior technique for synchronization over other methods, like R-peak synchronization that can be erroneously used, due to time correspondence. The highest and lowest normalized rms error of the digitized and original signals was found to be 13.49% and 9.85% for recording V1 and Lead III, respectively. The error found was expected because of the comparison of an image with many points in a single instant of time, in comparison to only one point as it is in a digital signal. The result obtained from the work presented here is that the ECG printout needs no longer to remain only as a graphical report, but could also be used for computerized analyses. PMID- 17282508 TI - Vessel extraction in coronary X-ray Angiography. AB - This paper describes a method to extract the vascular centerlines and contours in coronary angiography. The proposed approach associates geometric moments for the estimation of a "cylinder-like model" and relies on a tracking process. The orientation of the cylinder axis and its local diameter are computed from the analytical expressions of the geometric moments of up to order 2. Experimental results are presented on several images of two sequences that show the efficiency of the method. PMID- 17282510 TI - High Quality Appearance Models of Heart Sub-Components Based on MR Images. AB - High quality images have many uses, such as the testing of image processing algorithms and serving as templates for registration in image guided surgery. This work describes the creation of four high quality images or "appearance models", for 1. Myocardium, 2. Right atrium and ventricle, 3. Left atrium and aorta, and 4. Epicardial surface. The appearance models are created by registering and averaging together a series of high-resolution MR images of the same volunteer. These are then corrected to represent the average shape as determined from MR data of ten other volunteers. Thus, we show how single volunteer imaging can be combined with image registration to generate average shape appearance models with high resolution and signal-to-noise ratio. Our final data consist of four 3D average shape appearance models (each depicting one of the sub-heart components) with 1.5 x 1.5 x 1.5 mm3voxels and a signal to-noise ratio increase of 6.6 versus raw data. PMID- 17282512 TI - Comparison and Evaluation of PET/CT Image Registration. AB - Diagnosis, treatment planning and prognosis may be improved by combining functional data with anatomic location via PET/CT dual-modality image registration. The aim of this work is to reveal the spatial accuracy, reliability and speed of registration techniques used in GeminiTM PET/CT Imaging System, as a part of quality assurance program for clinical and research applications. A multi layer alignment bearing source device was used to validate PET/CT intrinsic alignment, as well as a Rando a Man phantom. A series of known transformations were performed to simulate different misalignment between PET and CT images. Two semi-automated registration techniques used to correct misalignment were assessed and compared quantitatively by measuring absolute distances between the centroids of corresponding fiducial markers in the registered volumes. Comparisons between independent and cross fiducial localization indicate that fused PET/CT is superior to visual correlation of PET and CT individually in identifying registration errors. The experimental and theoretical findings confirm that PET/CT hybrid system can produce robust intrinsic image alignment and accurate PET/CT image registration with careful user interaction. The maximum spatial error in our experiments is below 4 mm, and is better than the spatial resolution of the PET scanner used. This is considered to be sufficient for most PET/CT applications. PMID- 17282511 TI - A method of image registration based on its geometric character. AB - This paper aimed at building a model for the image registration of CT image and slice image. We used a registration method based on the geometric character of the outline of the image. This method need us do pretreatment to the image, in order to get rid of the noise and enhance the outline of the image, here we use time-frequency theory such as wavelet transformation a gray image fusion etc. The result of image registration shows that this method is fast a simple and effective. PMID- 17282513 TI - Wavelet shrinkage prefiltering for brain tissue segmentation. AB - This paper presents a method to segment brain tissue from T1-weighted Magnetic Resonance (MR) images. A modified BayesShrink method is utilized to filter the image in wavelet transform domain before segmentation, where the shrinkage strength is automatically adjusted with respect to noise level. Then the fuzzy c means clustering is applied to segment brain tissue into cerebrospinal fluid, gray matter and white matter. Comparison with other methods for brain tissue segmentation that remove noise using wavelet or non-wavelet based methods is made on phantom or real data and the advantage of the proposed method is demonstrated. PMID- 17282514 TI - Right Ventricle Extraction by Low level and Model-based algorithm. AB - In this paper we present an algorithm as the combination of a low level morphological operation and model based global circular shortest path scheme to explore the segmentation of the right ventricle. Traditional morphological operations were employed to obtain the region of interest, and adjust it to generate a mask. The image cropped by the mask is then partitioned into a few overlapping regions. Global circular shortest path algorithm is then applied to extract the contour from each partition. The final step is to re-assemble the partitions to create the whole contour. The technique is deemed quite reliable and robust, as this is illustrated by a very good agreement between the extracted contour and the expert manual drawing output. PMID- 17282515 TI - A vessel extraction algorithm based on point balance. AB - The article presents a concept of balance among image points based on the correlation of points and then develops a new binarization method for gray scale image, which can be used in vessel extraction of DSA images. A point is in balance only when its resistance counteracts the influence from the neighborhood, while noise breaks down such balance. By restoring the balance of every single point, the image can be a balance system, and most noise can been removed. The balance image turns into a binary image after segmentation by threshold. Experiments show that the algorithm has satisfactory effect on brain DSA images. PMID- 17282516 TI - Incorporating temporal information for ventricular contour detection in echocardiographic image sequences. AB - A novel way to incorporate temporal information with level set algorithm is proposed to counter the dropout problem when detecting ventricular contours in echocardiographic raphic image sequences. The temporal information ided embed- ed into the speed term of the level set equation. By identifying the ventricular contours as strong or weak segments, the weak segments are strengthened based on temporal information from neighboring frames. Hence disrupted heart wall boundary structure information due to dropout can be recovered. A Gaussian Mixture Model (GMM) is employed to compute thresholds separating the segments. A weight and a strengthening ng factor are used to control the information recovery process. Experimental results show the proposed method exhibits good performance when tracking the ventricular boundary in real echocardiographic data. PMID- 17282517 TI - Development of optical mapping system with real-time feedback stimulation in the heart. AB - Recent studies showed that electrical stimuli in the excitable gaps during ventricular fibrillation (VF) are important for defibrillation requiring low electrical energy. We developed an optical mapping system that measures action potentials and controls the timings and sites of electrical stimulus to verify the effectiveness of electrical stimulation in the excitable gaps. In this paper, the time delay of feedback algorithms with our optical mapping system was evaluated and the feedback stimulation protocols were operated using isolated rabbit hearts. We optically mapped electrical activity from a surface of Langendorff-perfused rabbit hearts stained with a voltage sensitive dye using high-speed video cameras. Acquiring image data triggered a timing pulse after 5.5ms using LED. In the experiment using isolated rabbit hearts, the timing delay was 10.2 ms. The velocity and direction of wave propagation was calculated in real-time using two reference points on a field of view. The two electrical stimulating points was selected by the action potentials on electrical stimulation points. The electrical shock was delivered on the point that was triggered earlier than the other point. PMID- 17282518 TI - Signal modeling with random scatterers for confocal microwave imaging. AB - Microwave breast tumor detection uses the electrical property contrast between normal tissues and malignancies to detect the latter in an early development stage. However, previous works on the microwave imaging uses 2-D or more complicated models of the breast and electromagnetic wave propagation. We present a computationally efficient and physically instructive electromagnetic wave channel modeling for confocal microwave imaging system for the breast tumor detection. The proposed model covers all of the factors that have been examined in the previous 2-D model, such as the radial spreading, path loss, partial reflection and transmission of the backscattered electromagnetic wave from the tumor cell. The characteristics of the reconstructed images of the tumor using the proposed 1-D model are compared with them of the previous 2-D FDTD method. Previous 2-D model of the cancerous breast utilizes the MRI-derived discretized cell model to simulate the realistic perturbation, but there has been no consideration on the system noise that can be detrimental to the reconstruction of the tumor. The effect of the system noise level to the reconstruction algorithm will be addressed as well. PMID- 17282520 TI - From medical images to finite grids system. AB - The development techniques of implementation of converting the medical slice images to 3-D finite element grids are discussed, and an integrated system based on ITK and VTK is built. The system can provide a series of functions including image reading, reduction, segmentation, reconstruction and finite element grids generation with flexible user's graphics interface. At same time, this system can also provide a powerful tool for the design, choice or assessment of image segmentation and reconstruction algorithm. PMID- 17282519 TI - Multiscale morphological analysis of the atherosclerotic carotid plaque. AB - The aim of this paper was to investigate the usefulness of multiscale morphological analysis in the assessment of atherosclerotic carotid plagues. Ultrasound images were recorded from 137 asymptomatic and 137 symptomatic plaques and were converted to binary images at low, middle and high intensity intervals based on structural morphology. Low images represent low intensity regions corresponding to blood, thrombus, lipid or hemorrhage, whereas high images describe the collagen and calcified components of the plaque. Middle image describe image regions that fall between low and high components. The morphological pattern spectra were computed and several classifiers like the K Nearest Neighbor (KNN), the Probabilistic Neural Network (PNN), and the Support Vector Machine (SVM) were evaluated for classifying these spectra into two classes: asymptomatic or symptomatic. The highest diagnostic yield achieved was 67% that is slightly lower than texture analysis carried out on the same data set. PMID- 17282521 TI - Surface modeling of complicated geometries with incomplete erroneous data points an extension to B-spline approach. AB - Based on the analogy between the B-spline curve modeling and the force-deflection behavior of a beam subjected to lateral point loads, an extension to the B-spline surface modeling method was introduced. The proposed method has strong extrapolating capability and can develop accurate surface models over an incomplete net of data points without affecting the original data. Extrapolation of the incomplete part of the data net is conducted simultaneously with interpolation of the existing part, with no need to recalculation. Approximation or data smoothing is a natural extension of the method, however, the smoothing intensity can be controlled continuously without reducing the number of spline intervals. The performance of the method was evaluated on some known analytical surfaces and produced more accurate results in comparison with the regular B spline approach. The results indicate that the proposed method can also filter erroneous data points and reconstruct the original surface successfully. PMID- 17282522 TI - Different approaches to the completion of the back-projection algorithm in image monitoring by electrical impedance tomography. AB - It is found that Electrical Impedance Tomography(EIT) is promising in its application to the clinical image monitoring and that the Back-Projection algorithm of EIT can meet the preliminary requirements of the real-time monitoring through our work. In order to improve the computed speed and the imaged resolution, different ways of completing the algorithm were tried in this paper. Moreover, it is shown that the impedance change due to physiological saline with the concentration of not more than 50 milliliter 0.9% can be detected and imaged by our system. The above result is helpful for our further work of image monitoring by EIT. PMID- 17282523 TI - The inverse problem of a passive multiband microwave intracranial imaging method. AB - A novel Microwave Radiometry Imaging System (MiRaIS) has been developed and experimentally tested for feasible brain activation "remote" imaging via contactless measurements. The technique implemented, is focused microwave radiometry with the use of an ellipsoidal conductive wall cavity for focusing and a sensitive radiometric receiver for the detection of the brain conductivity and temperature variation. All system attributes in terms of spatial resolution and detection depth have been theoretically calculated. Phantom experimentation as well as human tests using single frequency receivers, have shown promising outcome concerning the potential clinical value of the proposed system, which seems to be able to pick-up brain activation, possibly caused by cortex conductivity changes. Following this research, a four-frequency radiometric receiver with a broadband antenna operating within the range 1.3-3.1GHz has been recently developed. In the present paper, a method for retrieving the conductivity variation profile detected in the above mentioned frequencies is discussed. The inverse problem solution is in detail addressed and indicative measurements are used for the validation of the solution in question. The latter represents the estimation of the conductivity variation of cortical areas, corresponding to the detection depth and spatial resolution predicted by the forward problem solution. PMID- 17282524 TI - A new segmentation algorithm for the visible human data. AB - A new segmentation algorithm based on image algebraic operations for background removal of the Visible Human Data (VHD) has been proposed in the paper. The new algorithm has been implemented and tested. Both algorithm analysis and testing results have showed that the new algorithm could have better segmentation results on the VHD, with less algorithmic complexity and less computational complexity, compared with other known algorithms of background removal for the VHD. PMID- 17282525 TI - The Characterization and Imaging Behavior of a New Developed Paramagnetic Contrast Agent NMG2[Gd(TTDA-BOM)]. AB - [Gd(TTDA-BOM)]2-is a newly developed paramagnetic contrast agent.The ligand,TTDA-BOM,bears a benzyloxymethyl group so that the lipophilicity is increased. The water exchange rate for [Gd(TTDA-BOM)]2-is significantly higher than that of [Gd(DTPA)]2-and [Gd(BOPTA)]2 .In addition, the bound relaxivity of this Gd (III) complex has a remarkably high value with HSA. Therefore,it has potential to be used as a blood pool contrast agent for MRI. The aim of this study is to investigate the characterization and imaging behavior of NMG2[Gd(TTDA-BOM)] in normal rat livers and hearts using a 3T high field whole-body MR scanner.The high field MR scanner is expected to have a higher signal to noise ratio. The relaxivities r1and r2for [Gd(TTDA-BOM)]2-at 3T are 5.97 mM-1s-1and 7.99 mM-1s-1respectively, which are higher than those for [Gd(DTPA)]2(r1=4.64 mM 1s-1and r2= 5.08 mM-1s-1). The dynamic MRI studies show that there is marked enhancement in livers and hearts right after the bolus injection and the enhancement ratios keep high until two hours. In conclusion, [Gd(TTDA-BOM)]2-might have a good potential in both cardiovascular and hepatobiliary applications. PMID- 17282526 TI - Simultaneous Multi-slice Acquisition Using A Parallel MR Imaging System. AB - In this study, we attempt to reduce the Magnetic Resonance Imaging (MRI) scan time by combining SImultaneous Multi-slice Acquisition (SIMA) and blind source separation method in a phased array MR acquisition system[1-6]. Imaging was first acquired by a typical parallel imaging MR with multi-slice excitation RF profile; this will ends up with an overlapped image. By using blind source separation method which is addressed by Larkman [7] with information of these coil sensitivity distribution, one can further achieve n multiple slice images. The overall reduction ratio in acquisition time then will be the traditional reduction ratio R times this slice number n. By increasing the acceleration factor of Parallel Imaging, the SNR which involves ill-condition problem dropped severely and induce the obvious noise amplification in this reconstruction process [8-10]. Tikhonov regularization is then employed to treat this ill condition problem. In the preliminary study, we have successfully implement this technology by exciting two slices simultaneously in addition to the reduction factor R = 2 for a parallel MR system in in vivo experiment. In the conference, we will show results with higher number of slice number n for high spatiotemporal resolution on MR imaging system. In the future, more excited slices will be applied to this technique and the dynamic functional studies will also be used to test its capability. PMID- 17282527 TI - The influence of position to phase and magnitude detecting in medical magnetic induction imaging. AB - A 16-channel magnetic induction imaging system is introduced briefly. Highly precise phase and magnitude detecting method is applied to the information acquisition. The resolution of phase detecting is 0.003deg. The results of magnitude detecting also provide us with useful information. The characteristic curves are smoother than that of our previous system. One dimension results in different positions of the measurement region demonstrate the trend of variation of the detected signals. The positions of the object affect the results greatly and the trend of variation is regular. PMID- 17282528 TI - Finite-Element Electromagnetic Simulation of a Volume Resonator Coil for MR Neuroimaging. AB - The electromagnetic properties of a new volume resonator coil for MR neuroimaging are studied. This coil design is based on a resonator coil called PERES coil. A commercial software tool based on the finite-element method is used to compute the electric and magnetic fields for the quasi- static regime for a specific layout of two coils with 4 rectangular-shaped coils each. Computational experiments were done to calculate the optimal number of nodes and elements in the mesh. This commercial software tool allows us to clearly visualize the electromagnetic properties of the coil as a function of a particular configuration. PMID- 17282529 TI - A fast reconstruction method for magnetic induction tomography. AB - We developed a new perturbation method for tomograpy technique.In this technique, perturbation approach is employed for calculating the Frechet derivatives. The perturbation approach is more efficient as it needs only one forward calculation for each iteration. Theoretical analysis and numerical experiments show that this method has higher stability and computing efficiency. PMID- 17282530 TI - Multivariate correlation coefficient decomposition and its application to visual evoked potentials. AB - Interactions between cortical areas are crucial for cognitive functioning. We develop a method, called Multivariate Correlation Coefficient Decomposition, to access such interactions.By decomposing multi-channel mutual correlation coefficient(CC) matrix into individual CC, which is taken as mapping parameter, this method can map temporarily correlated sources activities. Both computer simulation and real Visual Evoked Potentials(VEP) test show that, compared to traditional power mapping, the presented method is sensitive to the combination of the correlated brain sources with different energy levels. Thus, it is of theoretical significance and of practical value. PMID- 17282531 TI - Infrared thermal image analysis in gradual approach for veins location. AB - The nurses do their phlebotomized work or the transfusion for the patients according to their experiences usually. The infrared thermal image display system for the veins location is designed. In the system, a special infrared amplification lens is designed to make the image clear. A gradual approach method for the preponderant signals amplification is described in the veins image data processing. By using of the arithmetic program, the image of the veins details in the skin is displayed clearly in the computer screen. PMID- 17282532 TI - Analysis of human thermo response using 2nd order simulation circuit. AB - It is an important in bio-medical field to use a simulation technique which explain the bio-process in human body, heat transfer is one of human mechanical behavior. This paper emphasize on simulate the Bio-heat transfer mechanism in the human body by a 2nd order electro-circuit, then study and analyze the human heat response under different conditions. PMID- 17282533 TI - An evaluation of lossless compression algorithms for medical infrared images. AB - Several popular lossless image compression algorithms were evaluated for the application of compressing medical infrared images. Lossless JPEG, JPEG LS,JPEG2000, PNG, and CALIC were tested on an image dataset of 380+ thermal images. The results show that JPEG-LS is the algorithm with the best performance, both in terms of compression ratio and compression speed. PMID- 17282534 TI - A Correction Method of Medical Thermography's Distortion. AB - A problem of temperature distortion of medical thermography of the limb ending which results from different infrared radiant intensity of points detected by infrared detector was discussed. Further the difference of the radiant intensity is caused by that of projecting angles of points. Subsequently through related theory and experiments this paper found that the temperature shown by thermography bears a Gauss attenuation relation to actual surface temperature of an object. A Gaussian Matching Arithmetic was put forward to correct this kind of temperature distion. Finally, by using this Arithmetic a temperature distortion of thermography of a finger was corrected and the results were exciting. PMID- 17282535 TI - Asymmetry analysis of breast thermograms with morphological image segmentation. AB - Breast thermography is considered particularly valuable for early breast tumors detection. The fast growing tumor has a higher metabolic rate and associated increase in local vascularization. It will cause the occurrence of some asymmetric heat patterns. Clinical interpretation of a breast thermogram is primarily based on the asymmetry analysis of these heat patterns visually and subjectively. In this paper, a new approach of asymmetry analysis of breast thermograms was proposed. The heat patterns are first segmented with mathematical morphology. The asymmetry analysis is performed both qualitatively and quantitatively according to the extracted features. The abnormality of a breast thermogram is clearly indicated by the features. PMID- 17282536 TI - Monitoring skin temperature in trained and untrained subjects throughout thermal video. AB - Skin temperature was monitored during a graded exercise to verify whether trained individuals have different skin thermoregulation from untrained ones. Eighteen subjects (10 trained; 8 untrained) were studied recording thermal videos of their skin temperature during the exercise. Training level was assessed by maximal oxygen uptake measurements. Trained individuals have better skin thermal control than untrained. PMID- 17282537 TI - Evolution of the surface temperature of pianists' arm muscles using infrared thermography. AB - Musculoskeletal disorders are very frequent among musicians. Diagnosis is difficult due to the lack of objective tests and the multiplicity of symptoms. Treatment is also problematic and often requires that the musician stop playing. Most of these disorders are inflammatory in nature, and therefore involve temperature changes in the affected regions. Temperature measurements were recorded with an infrared camera. In this paper we present an overview of the temperature measurements made in the arms of 8 pianists during regular piano practice sessions. PMID- 17282538 TI - Reconstruction of thermal property distributions. AB - In this report, we propose to reconstruct thermal properties such as thermal conductivity and thermal diffusivity in addition to the mechanical properties for diagnosis and treatment (planning). Temperature distribution can be measured by ultrasonic imaging and MRI. Provided that the reference values of thermal properties are given in the ROI as initial conditions, by solving the simultaneous first order partial differential equations (PDEs) having the temperature distributions as inhomogeneous coefficients, we can determine the thermal property distributions. Simulations and phantom experiments were conducted. PMID- 17282539 TI - Muti-criterion Optimization Algorithm for X-ray Phase Contrast CT imaging. AB - X-ray phase contrast imaging method is able to show microstructure inside soft tissues with weak absorption in a radiograph mode. X-ray phase contrast CT is being under study. We propose a multi-criterion optimization approach to reconstruct the object from phase contrast images. Our reconstructed results show that the method can differentiate boundary of microstructure of fly very clearly. Comparison of the reconstructed images indicates that this algorithm gives finer resolution and better smoothness over the conventional ones. PMID- 17282540 TI - A lattice estimation approach for the automatic evaluation of corneal endothelium density. AB - The analysis of microscopy images of corneal endothelium is routinely carried out at eye banks to assess cell density, one of the main indicators of cornea health state and quality. We propose here a new method to derive endothelium cell density that, at variance with most of the available techniques, does not require the identification of cell contours. It exploits the feature that endothelium cells are approximately laid out as a regular tessellation of hexagonal shapes. This technique estimates the inverse transpose of a matrix generating this cellular lattice, from which the density is easily obtained. The algorithm has been implemented in a Matlab prototype and tested on a set of 21 corneal endothelium images. The cell densities obtained matched quite well with the ones manually estimated by eye-bank experts: the percent difference between them was on average -0.1% (6.5% for absolute values). Albeit the performances of this new algorithm on the images of our test set are definitely good, a careful evaluation on a much larger data set is needed before any clinical application of the proposed technique could be envisaged. The collection of an adequate number of endothelium images and of their manual densities is currently in progress. PMID- 17282541 TI - Multidimensional displacement vector measurement methods utilizing instantaneous phase. AB - In this report, we propose two new methods for measuring multidimensional displacement vector using instantaneous ultrasound signal phase, i.e., the multidimensional autocorrelation method and the multidimensional Doppler's method. In order to realize high measurement accuracy, respective displacement vector measurement methods are combined with our proposed useful lateral modulation method, i.e., the lateral Gaussian envelop cosine modulation method. We further report measurement accuracy evaluated through simulations. These methods can be applied to tissue strain measurement, blood flow measurement, sonar measurement, etc. PMID- 17282542 TI - Study and implementation of a novel ultrasound imaging technique combining digital beamforming with synthetical aperture. AB - Aiming at higher performances and lower cost of an ultrasonic imaging system, a novel digital imaging approach was proposed, which combines the dual beamforming technique to double frame rate with the synthetical aperture technique to halve receive channels. Besides theoretical analyses and simulations, its hardware implementation was discussed in detail, embodied and finally tested on a real ultrasonic imaging system. The experimental results show that with this approach, system cost can be remarkably reduced without lowering the frame rate and image quality. PMID- 17282543 TI - High Frame Rate Ultrasonic Imaging System Based-on Linear Frequency-Modulated Signal. AB - The high frame rate (HFR) ultrasonic imaging system, which is developed with limited diffraction beams, constructs images at a high frame rate. Because of one transmission for constructing image, the system suffers from lower signal-to noise rate (SNR). The proposed method uses linear frequency-modulated signal (or chirp) as excited signal. For the higher time-bandwidth (TB) products available in the chirp, a compressed pulse response is obtained by passing the received signal through a related matched filter. The results show that the higher SNR of the system offered by chirp excitation gives improved image quality. PMID- 17282544 TI - Retinal Blood Velocity Measurements using Laser Speckle Imaging. AB - Retinal blood velocity measurements using laser speckle imaging were obtained using a modified fundus camera. The effect of blood oxygen saturation on retinal blood velocity was examined using a rabbit model. PMID- 17282546 TI - Reconstruction of 3D Elasticity Images from a Layered Element Chain. AB - Elasticity imaging is a novel technique that can reveal intrinsic mechanical properties of soft tissue. This paper proposes a new finite element approach to reconstruct elasticity images. Based on the real time data capturing capability of ultrasound, we propose a layered element chain algorithm to compute the distribution of Young's moduli in a region of interest. This approach employs pre calibrated moduli as its input instead of using boundary pressure conditions which are usually not easy to obtain. PMID- 17282545 TI - A content-based retrieval system for endoscopic images. AB - Based on the research of low-level visual image features including color clustering, color texture and shape, a new image retrieving method using multi feature fusion and relevance feedback to retrieval images is proposed. By setting up a prototype system to evaluate the performance of the proposed method, the results illustrate that the method can retrieve endoscopic images more effectively, accurately and quickly than the one based on single feature because of its flexible ability to combine features and interactive relevance feedback. PMID- 17282547 TI - Medical Imaging in the [1012Hz - 1014Hz] Domain. AB - Enormous efforts are made to achieve advances in image quality and acquisition time of today's standard medical imaging modalities as X-ray fluoroscopy, computed tomography, magnetic resonance and ultrasound. However, new principal diagnostic insights cannot be expected from the linear extension of the physical principles of these methods. In this paper a review is given on imaging modalities in the 1012Hz - 1014Hz domain that include new physical principles as terahertz and diffuse optical imaging or well known principles - that had been rejected some years ago and are recently raised to interest by detector advances - as thermography. PMID- 17282548 TI - Hand pressure estimation by image entropy for a real-time breast self-examination multimedia system. AB - The degree of hand pressure applied on a breast determines the possibilities of lump detection during breast self-examination. In this paper, a method for estimating hand pressure is presented by means of analysing image entropy for an image sequence obtained through a Web camera. This is achieved by, firstly, calculating the difference between the current and initial images followed by the entropy of the difference. The estimated pressure is proven to be accurate through a human-like silicon breast experiment. The dynamic model of the breast is set up, close to Hook's rule, by means of verification of the proposed pressure estimation. The algorithm is simple and the calculation is limited in a local region of the images, which is beneficial for real-time realization. PMID- 17282549 TI - Contrast-modulated Nonlinear Diffusion for X-ray Angiogram Images. AB - In this paper, we present a new method for X-ray angiogram images enhancement using a contrast-modulated nonlinear diffusion. The original nonlinear diffusion is gradient driven, which leads into much dependence on the accurate estimation of the edge. However, it is very difficult to get the accurate estimation of edges for X-ray angiogram images, which are characterized with complex background. So it is necessary to do some improvements to this model. By designing a new concept of contrast space according to the characteristics of these images, we change the original nonlinear diffusion into contrast-modulated nonlinear diffusion. Compared with the traditional method, this new approach is proved to have a better performance of enhancement. PMID- 17282550 TI - Optically encoded nanoparticles for detecting single biomolecules and viruses: rapid analysis of two-color colocalization data by high-speed computing. AB - Nanometer-sized particles such as luminescent quantum dots (QDs) and energy transfer nanoparticles have unique optical, electronic, and structural properties (e.g., signal brightness, photostability, and multicolor light emission) that are not available from traditional organic dyes and fluorescent proteins. Here we report the use of color-coded nanoparticles and dual-color fluorescence correlation for real-time detection of single native biomolecules and viruses in a microfluidic channel. Using green and red nanoparticles to simultaneously recognize two binding sites on a single target, we show that individual molecules of genes, proteins, and intact viruses can be detected and identified in complex mixtures without target amplification or probe/target separation. When combined with high-speed computing such as image segmentation and parallel computing, these nanoparticle probes raise new opportunities in molecular diagnostics, bioterrorism agent detection, and intracellular single-molecule imaging. PMID- 17282551 TI - A New Method to Get More Robust MTF Curve. AB - This paper presents a method to locate wire center on performance phantom image to get MTF curve during CT spatial resolution measurement. We get the circular edge of the wire area by automatic threshold segmentation and edge tracking. After that, using Hough transform, we can locate the wire center automatically. Compared with old method, it's immune to noise and more convenient to operate. Experimental results show that new method is accurate and gets less standard deviation sum of x-coordinate and y-coordinate of center point. PMID- 17282552 TI - A Reconfigurable System-on-chip Architecture for Medical Imaging: Preliminary Results. AB - In this paper, we present a reconfigurable system-on-chip architecture targeted mainly to medical imaging applications. By combining general purpose processors and FPGA-based hardware, and integrating the whole system into a single FPGA chip, we were able to build a compact system without sacrificing processing power and flexibility. A prototype board based on the proposed architecture was built and evaluated in a digital X-ray imaging system. Preliminary results were presented and showed that the architecture could satisfy real-time digital X-ray imaging requirements. PMID- 17282553 TI - An effective image measurement in brachial flow-mediated dilation response analysis. AB - Non-invasive cardiovascular measurements are used to evaluate cardiovascular diseases early and to cure early. By using various evaluation methods of cardiovascular features to diagnose cardiovascular disease.Flow-mediated dilation (FMD) evaluated by Ultrasound offers a mechanism to characterize endothelial function and, therefore, may play a role in the diagnosis of cardiovascular diseases. Cardiovascular endothelial is intermedia between blood and cardiovascular muscle. It has important effect for keeping balance of the environment in vessel. Nitric Oxide (NO) is the most important fact. Many cardiovascular diseases, like high cholesterol, high blood pressure, coronary heart disease, diabetes, smoking, is the cause of endothelial dysfunction. We design a series of images analysis methods to compute the change of cardiovascular radius in ultrasound images for evaluating endothelial function instead of measuring by-hand. We use B-mode ultrasound system to measure brachial cardiovascular radius. Then we capture the images by image capture card 10 images per second. We evaluate the average radius of brachial cardiovascular radius before we cut off blood flow. And we evaluate the maximum radius of brachial cardiovascular radius after we cut off blood flow and release it. Using the two radii we can compute the FMD value to evaluate endothelial function. First, we use Hough Transform to detect possible center possible of vessel. Then we use edge-reserved filter to filtrate speckle noise and preserve edge. After filtrating noise, we utilize Laplacian of Gaussian to detect edge-points. PMID- 17282554 TI - A novel implementation of watershed transform using multi-degree immersion simulation. AB - A novel implementation of watershed transform using a multi-degree immersion simulation is presented in this paper. The method is based on the improvement of traditional watershed by simulating immersion, which is originally proposed by Vincent & Soille in 1991. By changing the simulation procedure to multi-degree, which means the flood step is different on each degree of intensity, the proposed implementation resists the over segmentation problem effectively. After conducting a comparison of both the computing time and memory cost between the proposed method and a topographical distance based implementation, we draw the conclusion that the presented implementation achieves more accurate result with lower cost. PMID- 17282555 TI - Comparison of B-mode, M-mode and Hough transform methods for measurement of arterial diastolic and systolic diameters. AB - Measurements of arterial diameter during the cardiac cycle are increasingly used to study the mechanical properties of the arterial wall and changes associated with disease. In this paper, diastolic and systolic diameters of the carotid arteries were estimated from ultrasound imaging using the following three different procedures: a/ B-mode imaging with region tracking and block-matching, b/ M-mode imaging with automated edge detection and c/ automatic segmentation of the arterial lumen at diastole and systole using the Hough transform. Transverse images of the carotid artery were used, in which the arterial lumen has an almost circular appearance. The values for systolic and diastolic diameters estimated with the Hough transform, 0.69±0.04 and 0.61±0.06, respectively, were closer to those estimated with B-mode and motion tracking, 0.75±0.07 and 0.67±0.09. A large difference was found for a subject with an atherosclerotic vessel wall. It is concluded that the Hough transform can be efficiently used to automatically segment healthy arterial wall lumen from B-mode ultrasound images of the carotid artery, assuming a circular shape. In atherosclerotic vessel walls the assumption for circular shape may no longer be valid, and thus the use of an elliptical shape may be more appropriate. PMID- 17282556 TI - ECG Gated Ultrasonic Small Animal Imaging. AB - Echocardiography is a routine clinical procedure to diagnose cardiac functions. The organic structure of the mouse is similar to that of human so that murine echocardiography has potentially become an effective tool for the assessment of human cardiovascular disease. However, clinical ultrasonic imaging systems are not suitable for murine cardiac imaging due to its limited spatial and temporal resolution. Thus, high frequency ultrasonic imaging (≥ 20 MHz) is necessary in order to provide spatial resolution at the order of 100 μm. Furthermore, due to the lack of transducer arrays at such a high frequency, single-element transducer with mechanical scanning is typically used. Thus the frame rate is insufficient for imaging the quick motion of the mouse. In this paper, a high frequency ultrasonic imaging system with electrocardiography gating is built in order to provide both high spatial resolution and high temporal effecting resolution. The system utilizes the R-wave trigger signal from murine electrocardiography. Image data are acquired in either the block scanning mode or the line scanning mode. In block scanning, murine cardiac images in systole and diastole can be retrospectively reconstructed with a short data acquisition time. In line scanning, on the other hand, images during the entire cardiac cycle can be obtained. It is demonstrated that the effective frame rate can be up to 2 kHz, which is only limited by the pulse repetition rate of the system. PMID- 17282558 TI - Exponential Entropy Driven HUM on Knee MR Images. AB - A very important artifact corrupting Magnetic Resonance Images is the RF inhomogeneity. This kind of artifact generates variations of illumination which trouble both direct examination by the doctor and segmentation algorithms. Even if homomorphic filtering approaches have been presented in literature, none of them has developed a measure to determine the cut-off frequency. In this work we present a measure based on information theory with a large experimental setup aimed to demonstrate the validity of our approach. PMID- 17282557 TI - The Implementation of a Stand-alone Video Tracking and Analysis System for Animal Behavior Measurement in Morris Water Maze. AB - In this paper, a digital image tracking and analysis system based on FPGA is presented. The goal of this research is to build an animal tracking system with a new algorithm for Morris water maze experiment application. Our tracking algorithm can track animal motion and is insensitive to environment brightness change. The system can process the high-resolution image up to 700X480 pixels in real-time speed. We can analyze tiny animal behavior change precisely. This system is very compact and is portable. Compare with other similar device, our system is standalone operation without the necessary of a personal computer. PMID- 17282559 TI - The application of watershed algorithm in the initial contour selection of mumford-shah model. AB - The image segmentation based on active contour model is currently a hot-spot issue, among which Mumford-Shah model is an important method. To solve the problem of unbearable computing time, this paper intends to combine Mumford-Shah model and Watershed algorithm in the image segmentation. Specifically, the image will be segmented firstly through Watershed1algorithm and then the border produced will be the initial contour of Mumford-Shah model. Since Watershed algorithm has the advantage of segmenting the target object from the complex background, the contour produced thereupon is very close to the border of the target object. After that, Mumford-Shah algorithm is used to segment the image with the contour produced thereupon as the initial contour. In this way, the iterative time is greatly reduced and a good result can be expected. PMID- 17282560 TI - Surrounding inhibition in rat somatosensory cortex during noxious electrical stimulation of the sciatic nerve. AB - Surrounding inhibition is a physiologic mechanism to focus neuronal activity. Here we applied optical imaging of intrinsic signal to observing the temporal spatial characteristic of rat primary somatosensory cortex during graded electrical stimulation of the sciatic nerve (5 Hz, duration of 2 s, 0.5 ms pulse, 1 and 10 muscle twitching threshold). We found that the magnitude and change duration (time course) of the optical signal were larger and longer with the intensity raising. The spatial extent was also wider under noxious electrical stimulus. Meanwhile, we found the inverted optical signal changes in the regions surround the activated primary somatosensory cortex. This phenomenon was similar to the inhibition surrounding focal itcal events observed by optical imaging of intrinsic signal. It suggests the surrounding inhibition under noxious electrical stimulus was probably induced by the excess discharge of excited neurons or it may provide finer discrimination during the noxious stimulus and support the view that the role of somatosensory cortex in pain localization is to finely discriminate the stimulus site. PMID- 17282561 TI - Optimized Collimator Designs for Small Animal SPECT Imaging With a Compact Gamma Camera. AB - The aim of this study to design optimized pinhole and parallel-hole collimators for the development of a high-resolution microSPECT system using a compact pixelleted scintillation detector. The detector has a field-of-view of 11cm with pixellated crystal elements of 1.0mm pixel size and 1.12mm pixel pitch. The relative resolution and sensitivity advantages of pinhole and parallel-hole collimators for mice and rats imaging were investigated using analytic formulations and Monte Carlo simulations. The optimized collimator designs were obtained by maximizing the system detection efficiency for a given object resolution. The collimator designs were optimized for 140 keV incident gamma photons. Our results indicate that this small field-of-view compact detector fitted with a conventional high-resolution parallel-hole collimator with 4cm hole length and 1.2mm hex hole-size couldn't provide better than 2 mm resolution for mice and rats imaging. However, a pinhole collimator with 10cm focal length and 1.0mm aperture size with keel-edge design of 0.5mm channel-height can provide the desired resolutions for imaging mice and rats. The relative efficiency is about 2 times higher than that of the parallel-hole collimator for imaging mice at the distance of 3cm from the collimator. In conclusion, pinhole collimator is superior to parallel-hole collimator and requires sophisticated optimal designs with high-resolution compact gamma camera for small animal imaging. PMID- 17282562 TI - L-type calcium channels mediate synchronized spontaneous Ca2+spikes in cultured cortical networks. AB - We have detected synchronized spontaneous Ca2+spikes in cultured cortical networks in the presence of Mg2+. The synchronized spontaneous Ca2+spikes are synaptically driven, as it is blocked by tetrodotoxin (TTX), and by the glutamate receptor antagonist CNQX/APV. The oscillatory activity is not influenced by GABAAreceptor antagonist picrotoxin, suggesting that they entirely rely on glutamatergic neurotransmission. We have also found that these Ca2+spikes are dependent on an influx of extracellular Ca2+but are independent of mobilization of Ca2+from intracellular Ca2+stores. Ca2+entry occurred primarily through L-type voltage-gated calcium channels (VGCCs), since nifedipine completely blocked these Ca2+spikes. PMID- 17282563 TI - X-ray phase-contrast imaging: phase reconstructions. AB - Clinical x-ray imaging has always been based on the biological tissue's differences in x-ray attenuation ever since Roentgen discovered x-ray over 100 years ago. However x-ray-tissue interaction causes x-ray phase changes as well. We have identified the four clinically important factors that affect the x-ray phase visibility in clinical imaging. These factors are: body part attenuation, the spatial coherence of incident x-rays from an x-ray tube, the polychromatic nature of the x-ray source, and radiation dose to patients for clinical applications. A Wigner-distribution-based theory of phase-contrast imaging is presented to account for the effects of these four factors. Numerical simulations for x-ray phase-contrast mammography for phase reconstruction are described. PMID- 17282564 TI - Classifying uterine myoma and adenomyosis based on ultrasound image fractal and texture features. AB - The classification of the uterine myoma and adenomyosis from their ultrasound images mainly depends on doctors' experience and lacks objective criterions. Here a novel classification method is proposed using the multiresolution analysis and the orientational fractal analysis. Firstly, texture features under various resolutions and orientational fractal features are obtained from ultrasound images. Then the feature selection (FS) process is implemented using the sequential forward selection algorithm (SFS). Finally a classifier based on the support vector machine (SVM) is set up to classify the images into normal (Nor), myoma (Myo) and adenomyosis (Ad) cases. From the application of 27 Nor, 45 Ad and 74 Myo cases, it is showed that orientational fractal features and some multiresolution texture features are sensitive to the uterine Myo and Ad classification. The SVM classifier with the selected features may be useful in the practical classification. PMID- 17282565 TI - A Weighted Least Squares Reconstruction Method for PET Data Using Nonlinear Anisotropic Diffusion Regularization. AB - Due to the inherent ill-posedness of PET image reconstruction, the reconstructed images will have noise and edge artifacts. A roughness penalty is often imposed on the solution to control noise. In this paper, we propose a new weighted least squares (WLS) image reconstruction method for PET based on nonlinear anisotropic diffusion (AD) regularization. The use of AD is because it is extremely effective for reducing noise in 2D images while preserving edges. The weighted factor is used to balance data consistency and regularization terms. The application of the proposed approach to simulated and real PET emission data show that it more effective than the common WLS algorithm, especially for noisy projection data. PMID- 17282566 TI - Data Correction for Gantry-tilted Local CT. AB - Gantry-tilted helical multi-slice computed tomography (CT) refers to the helical scanning CT system equipped with multi-row detector operating at some gantry tilting angle. Its purpose is to avoid the area which is vulnerable to the X-ray radiation. The local tomography is to reduce the total radiation dose by only scanning the region of interest for image reconstruction. In this paper we consider the scanning scheme, and incorporate the local tomography technique with the gantry-tilted helical multi-slice CT. The image degradation problem caused by gantry tilting is studied, and a new error correction method is proposed to deal with this problem in the local CT. Computer simulation shows that the proposed method can enhance the local imaging performance in terms of image sharpness and artifacts reduction. PMID- 17282567 TI - Computer-Aided Diagnosis Applied to 3-D US of Solid Breast Nodules by Using Principal Component Analysis and Image Retrieval. AB - Textural features have been shown to be valuable in tumor diagnosis. This study combines three practical textural features in ultrasound (US) images, i.e. spatial gray-level dependence matrices (SGLDMs), gray-level difference matrix (GLDM) and auto-covariance matrix, to identify breast tumor as benign or malignant. The textural features were extracted from 147 3-D ultrasound cases and each case composes a volume of interest (VOI). Usually, the larger region of interest (ROI) sub-image contains considerable textural information. Thus the feature vector extraction utilizes only the adjacent frames with the largest ROI sub-image. The textural features always perform as a high dimensional vector that is unfavorable to differentiate breast tumors in practice. The principal component analysis (PCA) is used to reduce the dimension of textural feature vector and then the image retrieval technique was utilized to differentiate between benign and malignant tumors. The proposed computer-aided diagnosis (CAD) system differentiates solid breast nodules with a relatively high accuracy in the US imaging and helps inexperienced operators avoid misdiagnosis. PMID- 17282568 TI - FDTD Simulation of Nonlinear Ultrasonic Pulse Propagation in ESWL. AB - The extracorporeal shock wave lithotripsy (ESWL) has come into wide use due to its non-invasive advantage. However, as for the shock wave propagation in human body in relation to practical lithotripsy, there are a few studies on numerical simulation based on models conforming to practical situations. In this paper we report a numerical method of finite difference time domain (FDTD) for analyzing ultrasonic pulse nonlinear propagation in human body tissues and demonstrated it through an experiment of Reichenberger's ESWL in water. PMID- 17282569 TI - Gantry tilted Tilted Plane Feldkamp Type Reconstruction Algorithm. AB - An approximate image reconstruction method for gantry tilted multi slice computed tomography (MSCT) is presented in this paper, which extends the Feldkamp cone beam reconstruction algorithm to overcome its inaccuracy problem caused by large cone angle. This is done by tilting the reconstructing planes to minimize the cone angle and optimally fitting the spiral segment of the source. It is shown that the image reconstruction performance of the proposed algorithm is superior to that of the Feldkamp reconstruction algorithm. Because a 3D projection data set is employed, the proposed algorithm can use the projection more efficiently than 2D approximate reconstruction algorithms. With the reduced distance from the X-ray source to the reconstruction plane, the maximum pitch value of the proposed algorithm is larger than that of conventional Feldkamp algorithm. The proposed algorithm can archive higher volume coverage speed than Feldkamp algorithm. PMID- 17282570 TI - Constrained least squares filtering for ultrasound image deconvolution. AB - This paper uses a new tissue model, which incorporates random fluctuations of the tissue signal within the received ultrasound radio frequency (RF) echo signal, to propose an ultrasound image deconvolution algorithm for improving the quality of ultrasound images. Using this model, we propose a modified version of the classical regularization method which combines optimal Wiener filter and constrained least squares (LS) filtering algorithm for estimation of the tissue signal. The performance of the algorithm is evaluated by simulation. The deconvolved images can show significant improvement in both the speckle reduction and the contrast ratio. PMID- 17282571 TI - The modified convolution models of ultrasound echo signal. AB - The ultrasound convolution model is addressed in this paper. Image formation process in the traditional model is expressed as a spatial-temporal convolution between the tissue signal and the ultrasonic system response. However, with the understanding of the existing widely-applied convolution model, we present modification since it omits the acoustical interactions inside the tissue. Consequently, under further analysis on the interactions and the reasonable assumptions of ultrasound propagations, two modified models are proposed, in which one takes the incident interaction into account and the other focuses on the backscattering interaction. PMID- 17282572 TI - Ultrasonic diffraction tomography by pulse-plane wave: experimental result by frequency synthesis method. AB - Diffraction tomography is a technique for imaging with acoustic fields in which parameter, such as reflective index, sound velocity, etc., can be mapped from scatter wave resulting from insonifying the object with a plane wave at a single temporal frequency. By solving the direct scattering problem, the scattered field can be presented in term of scattering parameters. Different inversion techniques can be applied to take advantage of the linearization process of the non-linear wave equation describing wave propagation in heterogeneous media under a limited class of scattering. Specifically, when the scattering effect is weak, one can invoke the Born or Rytov approximation and thus derive the generalized Fourier slice theorem to reconstruct the cross-section of the insonified object. Although diffraction tomography is a promising technology for medical application as it provides a quantitative ultrasonic image, its realization toward medical use is still far-to-go, and this may be due to the complexity of the hardware involved. In this research we investigate a potential use of diffraction tomography for medical application by using a delicate-designed ultrasonic computerized tomographic system. The contribution of the paper is that we have purposed to frequency synthesis method (FSM) that uses 3 frequency components of the Fourier transform of scattered filed, i.e. the center frequency and the -3 dB from center frequency of both side, to fill Fourier space for the generalized Fourier slice theory. The reconstructed ultrasonic image from such theory provides a very promising result. PMID- 17282573 TI - Median filters used for volume reconstruction in freehand 3-d ultrasound. AB - Freehand 3-D ultrasound imaging has been playing an important role in obtaining entire 3-D impression of tissues and organs. Reconstructing a sequence of irregularly located B-scan images into a volume data set with regular voxel arrays is one of key procedures for visualization and data analysis. In this study, we investigated the feasibility of median filters for volume reconstruction in freehand systems. Three median filters were proposed to filter noises and obtain voxel intensities. Qualitative and quantitative comparison results were presented to demonstrate the performance of median filters for volume reconstruction. Compared with conventional distance weighted (DW) interpolation, the three median filters were able to preserve more image details and reconstruct volume data with better quality. PMID- 17282574 TI - Experiment studies of iodinated oil nanometer ferrofluid retention in rabbit liver. AB - To study possibility for iodinated oil nanometer ferrofluid retention in rabbit liver. 131I- iodinated oil nanometer ferrofluid were injected into liver right lobe through portal vein in 5 rabbits... - calibrate meter showed continuous.. counts in the region injected. Then the relative metabolic parameters were calculated. Left lobe livers, right lobe livers and lungs of the rabbits were examined in pathology, and the right lobe livers were examined by electron microscope. Five rabbits injected purely 131Iiodinated oil were designated as control group. Single metabolic mode was found in the rabbits in nanometer ferrofluid group. The biological half-life of 131I- iodinated oil nanometer ferrofluid was not different from control group's slow metabolic portion. But control group's rapid metabolic portion were eliminated in a higher speed, range from 8% to 44%. More damage was found in nanometer ferrofluid group's right lobe livers. 131I- iodinated oil nanometer ferrofluid possess the opportunity of local retention in human body and further study is worthwhile. PMID- 17282575 TI - Parallel OSEM Reconstruction Algorithm for Fully 3-D SPECT on a Beowulf Cluster. AB - In order to improve the computation speed of ordered subset expectation maximization (OSEM) algorithm for fully 3-D single photon emission computed tomography (SPECT) reconstruction, an experimental beowulf-type cluster was built and several parallel reconstruction schemes were described. We implemented a single-program-multiple-data (SPMD) parallel 3-D OSEM reconstruction algorithm based on message passing interface (MPI) and tested it with combinations of different number of calculating processors and different size of voxel grid in reconstruction (64×64×64 and 128×128×128). Performance of parallelization was evaluated in terms of the speedup factor and parallel efficiency. This parallel implementation methodology is expected to be helpful to make fully 3-D OSEM algorithms more feasible in clinical SPECT studies. PMID- 17282576 TI - Implementation of Enhanced Image from Backscatter X-ray System. AB - Considerable attention has been focused on digital X-ray systems with transmission. However, only a few attempts have been made using X-ray backscatter system. It has difficulty that we have to reconstruct image from a little data in the image processing. Especially, it is necessary that the method correct error of detector effectively. That is the most important thing in the acquisition of X ray data. In this paper, it is that propose some data processing methods that correct error of detector, and we can recognize that the image reconstruction from a little data is effective. PMID- 17282577 TI - High frame rate ultrasound coded excitation. AB - an ultrasound imaging method which can achieve high frame rate and good SNR without sacrificing the resolution is proposed. Compared with other reported high frame rate imaging methods, the proposed imaging method can achieve 12dB SNR improvement while keeping the high frame rate. The methods are based on the application of the synthetic transmit aperture (STA) beamforming, coded excitation, defocusing delay and MisMatched Filter (MMF) technique. Field II has been applied to simulate the phantom result to verify the method. PMID- 17282578 TI - Registration of Vibro-acoustography Images and X-ray Mammography. AB - Image registration has been widely used for generating more diagnostic and clinical values in medical imaging. On the other hand, inaccurate image registration and incorrect localization of region of interest risks a potential impact on patients. Vibro-acoustography (VA) is a new imaging modality that has been applied to both medical and industrial imaging. Combining unique diagnostic information of VA with other medical imaging is one of our research interests. In this work, we studied the VA and x-ray image pairs and adopted a flexible control point selection technique for image registration. A modified second-order polynomial, which leads to a scale/rotation/translation invariant registration, was used. The results of registration were used to spatially transform the breast VA images to map with the x-ray mammography with a registration error of less than 1.65 mm. These two completely different modalities were combined to generate an image including a ratio of each image pixel value. Therefore, the proposed technique allows clinicians to maximize their insight by combining the information from x-ray mammogram and VA modalities into a single image. PMID- 17282579 TI - Characterization of Detector Scintillator Effect on Interventional Device Visualization in X-ray Fluoroscopy. AB - Flat panel detectors have a large number of parameters that affect fluoroscopy image quality. Scintillator thickness is very important and can be readily changed in fabrication. With increasing thickness, there is a degradation of MTF with spatial blurring but improved conversion efficiency. This design trade-off should be optimized for visualization. Using quantitative experimental and techniques, we simulated three detector models, including a direct detector and two indirect detectors with different scintillator thickness and investigated their effects on visualization of stent and guidewire. Detection performance was improved with the increasing scintillator thickness, especially at low exposure. With an idealized MTF, a direct detector performed fared better for stent detection as compared to guide wire detection. PMID- 17282580 TI - Cone beam X-ray scatter removal via image frequency modulation and filtering. AB - We present a novel method for rapid removal of patient scatter from cone beam (CB) projection images that requires no scatter measurement, physical modeling or strong assumptions regarding the spatial smoothness of the scatter distribution. METHOD: A modulator grid is placed between the imaged distribution and the detector that differentially frequency modulates primary and scattered photons. When photons travel through the grid, photons that originate directly from the CB source are modulated by a higher frequency than scattered photons that have more proximal, diffusely distributed sources. We employ non-linear Fourier domain filtering to attenuate the contribution of scatter to the image spectrum. The theoretical validity of the method is verified using linear analysis of planar sources and its performance is evaluated using a simulator based on this analytical model. RESULTS: Simulation experiments with an ideal modulator indicate that even unrealistically large amounts of scatter are almost entirely removed by this method. The recovered images are devoid of major artifacts and exhibit an RMS error of 10%. CONCLUSIONS: We have verified the theoretical validity of scatter removal via spatial frequency modulation. A disadvantage of the technique is that it will always produce a filtered image having at best 0.41 of the maximum detector resolution when maximum scatter rejection is desired. This is not a major consideration in most medical X-ray CB imaging applications using contemporary detector technology, especially since scatter often significantly reduces useful resolution. PMID- 17282581 TI - Searching binary sequences for coded excitation in medical ultrasound. AB - In this paper, the optimal binary sequences for coded excitation in B-mode medical ultrasound imaging are found by exhaustive search. The criterion is the mainlobe to sidelobe ratio (MSR) of the pulse compression. The pulse compression filter is designed based on an FIR least squares inverse filtering algorithm. The optimal binary sequences of length 13 to 28 are shown. A simulation of coded excitation using the resulting sequence is performed. The presented search results showed regularity in the structure of sequences with high MSR, which may be of help in the search of longer sequences. PMID- 17282582 TI - A general model of high frame rate imaging system. AB - A kind of high frame rate (HFR) 2D and 3D imaging method was developed in 1997. Because only one transmission is required to construct an image, this method can reach an ultra high frame rate (about 3750 volumes or frames per second for biological soft tissues at a depth of 200 mm). Compared with conventional delay and-sum (dynamic focusing) method, the new method uses the fast Fourier transform (FFT) algorithm. This may simplify the imaging system dramatically. But as the HFR method needs a special weighting on the received signal, the imaging system is still a little complicated. For example, a large number of amplifiers with different gains are required. In this paper, a more general HFR method is presented in the view of angular spectrum. Based on the study, the weighting process is replaced by Fourier transform. Computer simulation, which uses experimental data, is performed to verify the method. Results show that images constructed have the same high quality as the original HFR method while the system implementation of the method could be greatly simplified. PMID- 17282583 TI - Reduction of Beam-Hardening Artifacts in X-Ray CT. AB - Our goal is to decrease the importance of beam- hardening artifacts in X-ray computed tomography by address- ing the polyenergetic nature of the X-ray source. We use the same physical model as De Man and al [1]. We next adopt an estimation framework for the reconstruction: the attenuation coefficients are determined by a likelihood-based estimator. This approach leads to minimization of an objective function which exhibits a complex structure. Nonetheless, we develop a numerical procedure with satisfactory numerical efficiency : we use a nonlinear conjugate gradient method. The three major contributions of this communication are : the positivity of the solution ensured by a change of variables, the convergence properties of the algorithm, and a satisfying computation time. PMID- 17282584 TI - Real-time Reconstruction of Shear Modulus Distribution by Calculating Strain Ratio. AB - In this report, we reviewed our previously developed 1D reconstruction methods. By assuming 1D stress distribution, shear modulus distribution can be approximately obtained by evaluating ratios of measured strains generated in the direction of predominant tissue deformation. Since singularity might occur during calculating ratios, 1D implicit-integration is performed at the singular positions. The shear modulus distribution resulting from calculated ratio of the strains is also utilized as an initial estimate in 1D, 2D, and 3D implicit integration. To verify the usefulness of the 1D methods, the 1D methods are compared to conventional B-mode imaging and strain imaging. PMID- 17282585 TI - A Reconstruction Algorithm for Triple-Source Helical Cone-Beam CT. AB - For fast and exact CT reconstruction, we have conceptualized a triple-source helical cone-beam scanning mode, and formulated a backprojected-filtration (BPF) algorithm for that imaging geometry. The algorithm uses data from the three inter helix PI-arcs related to the inter-helix PI-lines and the minimum detection windows defined for the triple-source configuration. The proof of the formula is based on Tuy's inversion formula and the geometric relations of inter-helix PI lines. PMID- 17282586 TI - The effect of back-scan conversion on the texture features of ultrasound image. AB - Ultrasound is an important way of physical examination nowadays. Many literatures tried to find a quantified standard for diagnosing ultrasonic images; however, they neglected the effect of scan-conversion on image textures. This paper provides a preprocessing method, which practically conforms to the ultrasound image formats, and then compares the effect of the preprocessing method. Several images of sponges were used to evaluate the effect of the preprocessing because of their nearly homogeneous texture. It was found that the spread of standard deviations of the extracted features got narrower, at best 4 times, with preprocessing than that without preprocessing. The back-scan conversion is indispensable for the analysis of ultrasound images using features sensitive to depth and orientation. PMID- 17282587 TI - Imaging the Progression of Intra-tumor Heterogeneity in Prostate and Ovarian Xenografts Using Dynamic Contrast-Enhanced CT. AB - The purpose of this study is to measure the progressive intra-tumor heterogeneous physiological states for prostate (CWRrv) and ovarian (SKOV3x) xenograft mouse models. Dynamic contrast-enhanced CT was used to measure the change in a tumor's physiological state when transitioning from stage I (<7 mm diameter) to stage II (7-20 mm diameter). Images from stage I tumors are in the initial stages of angiogenesis: neovasculature growth. A radial heterogeneity begins to form with signs of angiogenic activity throughout the tumor. Stage II tumors develop both a saccular heterogeneity and a strong radial heterogeneity between periphery and core consistent with the effects of inflammatory and maturation processes. Imaging intra-tumor heterogeneity has the potential to track tumor stage and to be used as predictive factor in determining mortality rates. PMID- 17282588 TI - Development of a radiation therapy open-source platform. AB - Although several industrial radio-therapy planning solutions presently exist, most of them do not cover the customer needs sufficiently. The aim of this project is to develop an open source radio-therapy planning system that would offer the ground work for individual customer solutions. During the first stage of the project we concentrate on the development of a visualisation module, since it is required for other parts such as dose calculation and beam modelling. The visualisation module will feature 2D and 3D visualisation of CT-, MRI- and PET DICOM images, registration of the images using Normalised Mutual Information, 2D and 3D visualisation of the matched images as well as 2D and 3D user interaction. In this paper an outline for our system is presented as well as a registration module, which is the first part of the visualisation module. PMID- 17282589 TI - The study of digital ultrasonic bone conduction hearing device. AB - This paper introduces a novel hearing aid named artificial ultrasonic bone conduction hearing device, which is different from the traditional hearing aid in two sides: 1) sound conduction manner, 2) human perceptive principles. We focus on discussing the structure of the hearing aid and the research of frequency transposition algorithm. In addition, we design algorithm experimental platform and some sample electromechanical transducers. PMID- 17282590 TI - A New Method for Deblurring and Denoising of Medical Images using Complex Wavelet Transform. AB - Deblurring in the presence of non-Gaussian noise is a hard problem, specially in ultrasonic and CT images. In this paper, a new method of image restoration, using complex wavelet transform, has been devised and applied to deblur in the presence of high speckle noise. It has been shown that the new method outperforms the Weiner filtering and Fourier-wavelet regularized deconvolution (ForWaRD) methods for both ultrasonic and CT images. Unlike Fourier and real wavelet transforms, complex wavelet transform is nearly shift-invariant. This gives complex wavelet transform an edge over other traditional methods when applied simultaneously for deblurring as well as denoising. The proposed method is independent of any assumption about the degradation process. It is adaptive, as it uses shrinkage function based on median and mean of absolute wavelet coefficient as well as standard deviation of wavelet coefficients. Its application on real spiral CT images of inner ear has shown a clear improvement over other methods. PMID- 17282591 TI - Reconstruction Algorithm with Improved Efficiency and Flexibility in Multi-Slice Spiral CT. AB - There is a requirement for the development of CT to scan rapidly large longitudinal volume with high z-axis resolution. The combination of spiral scanning with multi-slice CT is a promising approach. The algorithm of image reconstruction for multi-slice spiral CT becomes, therefore, the main challenge. All algorithms known to the authors either need to derive the complementary data or work only for certain range of pitch values. This paper presents a novel reconstruction algorithm that can omit the derivations of the complementary data and work for arbitrary pitch values. The filter interpolation based on the proposed method is also easy to be implemented. The method is, thus, versatile. The results of computer simulations show that we can choose a combination of scan and filter parameters to meet the purpose of the examination. PMID- 17282592 TI - PET Image Reconstruction Using Mumford-Shah Regularization Coupled with L1Data Fitting. AB - In positron emission tomography (PET) image reconstruction, regularization methods are usually considered to suppress noise effects in reconstructed images. In this paper, we model this reconstruction problem in a new variational framework where the Mumford-Shah (MS) regularization coupled with recently developed L1 data fidelity term is adapted. In order to simplify the numerical computation, Ambrosio and Tortorelli's Gamma-convergence approximation is also employed to substitute the irregular parts (edge set) of MS functionals with the auxiliary smooth function. In numerical studies we compare our method with the "conventional" penalized least-square (PLS) algorithm with local nonquadratic Huber penalty. Results show both the feasibility and efficiency of the proposed algorithm. PMID- 17282593 TI - A thermal biosensor based on enzyme reaction. AB - Application of the thermal biosensor as analytical tool is promising due to advantages as universal, simplicity and quick response. A novel thermal biosensor based on enzyme reaction has been developed. This biosensor is a flow injection analysis system and consists of two channels with enzyme reaction column and reference column. The reference column, which is set for eliminating the unspecific heat, is inactived on special enzyme reaction of the ingredient to be detected. The special enzyme reaction takes places in the enzyme reaction column at a constant temperature realizing by a thermoelectric thermostat. Thermal sensor based on the thermoelectric module containing 127 serial BiTe thermocouples is used to monitor the temperature difference between two streams from the enzyme reaction column and the reference column. The analytical example for dichlorvos shows that this biosensor can be used as analytical tool in medicine and biology. PMID- 17282594 TI - Investigation of a phenylalanine-biosensor system for phenylketonuria detection. AB - Detection and prevention of Phenylketonuria (PKU) is becoming more and more important. However, the current methods are either imprecise or time-consuming. We propose a biosensor system based on phenylalanine ammonia-lyase (PAL) immobilized on an ammonia electrode to measure blood phenylalanine for PKU prevention. The biosensor exhibits good linearity from 10-5000μM and the response time is only about 2 minutes. It remains stable for at least 5 days and less than 20% drop of the original activity after ten day storage at 4□, while the service life of the biosensor could be up to 30 days. We also develop an intelligent system to ensure optimal conditions for operation and preservation of the biosensor and to make detection more convenient and reliable. All of these advantages indicate that the newly developed method could be a better one for solving the problems of PKU detection. PMID- 17282595 TI - A glucose oxidase sensor based on screen-printed carbon electrodes modified by polypyrrole. AB - A disposable amperometric biosensor for detecting blood glucose has been developed. The sensor is based on a screen-printed electrode prepared by electrochemical polymerization of pyrrole with glucose oxidase (GOD) and LiClO4 dopants. In citric acid buffer (pH5.0), GOD with negative charges is immobilized within electropositive polypyrrole matrices onto a carbon electrode surface. Afterward, the electron transfer mediator, potassium ferricyanide is immobilized by adsorption. Experimentally the compositions of pyrrole, LiClO4 and potassium ferricyanide are optimized. Amperometry is used for the determination of glucose concentration. Four microliters of glucose solution is needed for one test, and the response time of the sensor is 70s. The amperometric response of the enzyme electrode is linear in the range of 1-30 mM. PMID- 17282596 TI - Novel Shear-horizontal Surface Acoustic Wave Based Immunosensors Using SiO2Waveguiding Layers And Flow Injection Analysis. AB - Surface acoustic wave (SAW) devices based on shear-horizontal (SH) waves can be used as mass-sensitive immunosensors. This paper presents a novel SH-SAW sensor to detect anti-immunoglobulin (IgG) molecules by means of the antibody-antigen binding mechanism. The sensor system comprising dual delay lines was fabricated on 36° Y-X LiTaO3substrate. A SiO2layer was used as love mode waveguiding layers, well as insulating and chemically resistant protective layer. Moreover, flow injection analysis (FIA) method was used for continuous detection the protein molecules. The protein A was immobilized on the optional surface of the gold layer, then coupled with IgG to adsorb the antigens to be measured in the protein solution. The operational frequency of the system changed due to the interaction of antibody-antigen binding. The experimental result demonstrates the sensor has stable frequency response to the mass loading effect of the various anti-IgG concentrations with the sensitivity up to 3.3ng/ml/Hz. PMID- 17282597 TI - Polypyrrole Based Reporterless DNA/Protein Sensors. AB - Polypyrrole (PPy) is one of the important conductive polymers that are widely used in energy storage systems, biosensors and electronics. The electrochemical synthesis of PPy has advantages of simple process, mass production and low cost. In this study, polypyrolle were used to reporterlessly detect DNA and proteins. PPy thin films impregnated with probe molecules were deposited on both microelectrode and glassy carbon electrode surface by galvanostatic deposition method. Results demonstrated that PPy coated electrodes can be used for successful detection of DNA hybridization and antibody (Ab)-antigen (Ag) bindings. The experimental results also showed that the detection mechanism is probably due to the change of doping/undoping process of the conductive polymer after the DNA hybridization or antibody/antigen bindings. PMID- 17282598 TI - A Feasibility Study of PZT Thin-Film Microactuators for Hybrid Cochlear Implants. AB - Hybrid cochlear implants would integrate electric and acoustic auditory stimulation into a single unit to rehabilitate patients with sensori-neural hearing loss. Conceptually, hybrid cochlear implants consist of an electrode array, as in traditional cochlear implants, and an acoustic microactuator to generate pressure waves inside the cochlea. To enable hybrid cochlear implants, one must develop acoustic actuators small enough to be placed directly into the cochlea. In this study, the microactuators consist of a silicon diaphragm and a Lead-Zirconate-Titanate Oxide (PZT) thin film. Two actuators are tested. For the first actuator, the diaphragm size is 1.1 mm by 1.1 mm, the diaphragm thickness is about 12 m, and the PZT film thickness is 1 μm. The microactuator is tested in an unloaded condition (in air) and a loaded condition (with water and glass sheets) equivalent to a loading of 17 Pa. The microactuator presents a constant displacement of 16 nm, when the driving voltage is sinusoidal with amplitude of 5 V and frequency ranging from 500 Hz to 10 kHz. For the second actuator, the diaphragm size is 800 μm by 800 μm, the diaphragm thickness is 1 μm, and the PZT film thickness remains 1 m. The second actuator presents a displacement of 6 nm, when the sinusoidal driving voltage is 7.5 V in amplitude. Given that the motion of the stapes in normal hearing is 10 30 nm when the incoming sound pressure is 1 Pa (i.e. PMID- 17282599 TI - An implantable multifunctional needle type biosensor with integrated RF capability. AB - We report the development of an implantable multifunctional (glucose and cholesterol) needle type biosensor with integrated RF wireless circuitry for continuous in vivo monitoring of metabolites during short term stays in emergency room or intensive care unit. Silicon-based MEMS technologies are used for the fabrication of micro needle sensors. The whole device is covered by a biocompatible Parylene layer with opening structure at the active areas of electrodes. Electropolymerization of active biomolecules and conducting polymer provides in situ nanoscale physical entrapments of various oxidoreductases (Glucose oxidase and cholesterol oxidase) and functions as a viable matrix for the construction of micro amperometric biosensors. Hybrid CMOS fabrication processes are used to accomplish the 433 MHz ASK RF transmitter and receiver (0.18μm CMOS 1P6M process) and the data converter (0.35μm CMOS 2P4M process). We will present and discuss the detail design and the integrated system performance in this paper. PMID- 17282600 TI - Using Pt Dopant and Sol Gel Technology for Sensitivity Enhancement of TiO2/SnO2Humidity Sensors. AB - The sensitivity of the humidity sensor based on hybrid thin films of nanostructure TiO2/SnO2with Pt dopant was successfully increased. The humidity-sensitive materials, TiO2/SnO3, were prepared by sol gel technology. The microstructure of the sensing film after calcination was investigated by the Field Emission gun Scanning Electron Microscopy (FESEM) and revealed that the metal oxide hybrid had about 10 nm grain size. For studying the effect of Pt dopant on the humidity-sensitive responses, 1 ml to 10 ml of Pt standard solution was added into the colloidal solution. To compare the humidity sensor of Pt dopant with that of no Pt dopant, operational frequencies and electrode spacing were set under the relative humidity from 30 % to 95 % at the ambient temperature of 22 °C. We demonstrated that adding Pt dopant remarkably enhanced the sensitivity of TiO2/SnO2humidity sensor, and further decreased the TiO2/SnO2 resistance, which was 3.3 times lower than that without Pt dopant at the high humidity. PMID- 17282601 TI - Electrowetting of the blood droplet on the hydrophobic film of the EWOD chips. AB - Electrowetting-on-dielectric (EWOD) is a new method for handling droplets on the microfluidic chips. A most promising application for EWOD chips is the clinical diagnostics on human physiological fluids. This paper uses pure blood of rabbit as the experimental sample to test the wettability of the fluorocarbon polymer (p C:F) hydrophobic layer of the EWOD chips. The contact angle variation of the blood droplet is observed, which provides the possibility of pure blood driven on the chips of p-C:F film. Forty multiple magnification images of the blood droplet are acquired by delicate experiments and the contact angles are calculated based on image processing technology. The electrowetting of the blood droplets on the EWOD chips is analyzed and the experimental results are in good agreement with the theoretical calculation. PMID- 17282602 TI - Measurement of bioimpedance and cell viability during ischemia-reperfusion in the rat liver. AB - During liver resection and liver transplant, liver is damaged by ischemia reperfusion injury. Until now, there is no approved method to measure or predict the extent of liver injury during the operation. This is the preliminary study to make the real time monitoring system by quantification of bioimpedance and ischemiareperfusion reperfusion injury in liver. Sprague-Dawley rats were subjected to different periods of 70% partial hepatic ischemia (30, 60, 90 and 120minutes ischemia) and reperfusion. We measured changes of liver tissue bioimpedance (120Hz-100KHz) every five minutes. Cell viability was assessed by metabolic capacity of fatty acid (palmitic acid metabolic rate), ATP content and histological examination (H/E and TUNEL stain) at every 30 minutes interval during ischemia. PMID- 17282604 TI - Dual-channel photoplethysmography synchronization using a Barker sequence. AB - A Barker sequence is employed for the synchronization of two photoplethysmogram (PPG) channels. The correctness of this technique is demonstrated by recording a PPG signal, injecting a Barker sequence at the start of this trace and producing a delayed version of it. After preprocessing, cross-correlation techniques are utilized for accurate time alignment of the two traces. The algorithm can correct for any time misalignment as long as the synchronization sequence appears on both channels. PMID- 17282603 TI - The optimization of automatic fluidic system for cell-based biosensor. AB - Cells are equipped with a host of receptors that can convert chemical signals into electrical ones. Cell-based biosensors take cells as sensing elements for detecting the intracellular/extracellular microenvironment and some special characteristics of cells selves. This paper presents the design of the cell-based biosensor and optimization of the automatic fluidic system that makes it feasible to control the detecting process accurately, and the goal of which is to improve the maneuverability, repeatability and stability of sensor. In this study, excitable neural cells (rat cortical neurons or olfactory cell) are grown on top of the surface of the cell-based biosensor which is based on the principle of light-addressable potentiometric sensor. The optical beam is focused on the stimulated cell and the chip surface potential below the stimulated cell is recorded by the biosensor. Although the results demonstrate that this kind of cell-based biosensor has potential to monitor electrophysiology of living cell noninvasively for long term, the low signal-to-noise ratio so far hampers practical applications. PMID- 17282605 TI - Nondestructive Determination Method of Fruit Quantity Detection Based on Vis/NIR Spectroscopy Technique. AB - The objective of this study was to establish the relationship between Vis/NIR spectral and the major physiological properties of tomato-soluble solids content (SSC), acidity (pH) and fruit firmness. A total of 200 tomatoes were hand harvested and analyzed the spectra features using spectrophotometer. Principal component regression (PCR) and partial least squares (PLS) were used to develop the prediction models. The models for SSC (r= 0.90) of standard error of prediction (SEP) 0.19 Brix with three factors; pH r= 0.83) of SEP 0.09 with four factors; compression force(r= 0.81) of SEP 16.017N with six factors, and puncture force (r= 0.83) of SEP 1.18N with three factors, showed the excellent prediction performance. The Vis/NIR spectroscopy technique had significantly greater accuracy in determining SSC. It was concluded that it is possible to assess the quality characteristics of tomato. PMID- 17282606 TI - Dynamic Spectrum: a Brand-new Non-invasive Blood Component Measure Method. AB - We developed a brand-new method that fits the non-invasive blood component concentration measurement: the dynamic spectrum (DS) method. With use of this method, it was possible to eliminate the main interference of the individual discrepancy and extract some kinds of the blood component concentration by the analytic method. The definition, principle and measure method of the dynamic spectrum are presented in this paper. According to the theory, this method can get rid of main influence from the skin individual discrepancy theoretically. The achievement, study progress and remain work of this method are also introduced in this paper. Three kind of study of the DS are discussed in this paper. PMID- 17282607 TI - Poincare plot analysis for pulse interval extracted from non-contact photoplethysmography. AB - An analysis of pulse-to-pulse interval (PPI) derived from non-contact photoplethysmography (PPG) is performed using the Poincare plot technique. Eleven healthy volunteers participated in a protocol utilising both spontaneous and paced breathing methodologies with a customised non-contact PPG system to obtain adequate quality signals for a distance of 80mm between source and detector. An adaptive trough-searching algorithm (ATSA) is developed to extract the PPI which is effective in the presence of artefact during non-contact PPG measurement. A Poincare plot for each 5 minute period of the protocol shows significant pattern differences between spontaneous and paced breathing measurements. Geometric parameters extracted from the Poincare plot are shown to be sensitive to breathing interval changes and are a useful indicator for the variation of pulse rate variability measured using non-contact PPG. PMID- 17282609 TI - Optimization of bulk and surface biosensing in plane stratified configurations. AB - Various biochemical and tissue sensors utilize layered configurations to accurately measure the physical parameters (e.g. refractive index) of the suspension or tissue under investigation. The most sensitive techniques, like these based on well-known Surface Plasmon Resonance (SPR) phenomenon, are usually limited to surface sensing at the infrared and light wavelength bands. We present a new type of broadband absorption biosensing method, which utilizes Lossy Resonance Modes (LRM) in thin lossy film configurations and can be facilitated in a highly scalable and sensitive manner for both bulk and surface sensing in various frequency bands, from radio to light frequencies. PMID- 17282608 TI - Prospective venox feasibility study. AB - Venox is a propriety Venous Oximetry system, capable of measuring peripheral venous oximetry. In this ongoing study, Venox is being compared against mixed central venous oximetry during human cardiac surgery, with Fibre optic reflectance spectrophotometry being used as the gold standard, placed in the pulmonary artery. A background review of the Pulse oximetry, current venous oximetry techniques and the potential advantage of the VENOX system are discussed. Lessons learnt, Preliminary results, and future plans are included in discussion. PMID- 17282610 TI - A new concept for visual aids: "ViSAR" Visual Signal Adaptive Restitution. AB - This paper introduces a new visual device concept for patients with partially sight loss named Visual Signal Adaptive Restitution (ViSAR). This new concept adapt the signal visual itself to the patient's visual discomfort in real time. While most device tends to compensate for physiology anomaly, ViSAR concept allows to improve the patient-signal interaction and to favor an active vision. This system is the first interacting with eye movements and adapting signal to patient cognitive behavior. Patients do not do anything, ViSAR adapts visual signal to patient's visual discomfort without changing visual and referential reflexes. This new concept involves at the same time engineer, ophthalmologic, optometric and cognitive competencies. ViSAR concept offers a new visual device generation satisfying the growing needs in assistance technology. PMID- 17282611 TI - Visible/Near-infrared spectrophotometric blood typing sensor for automated near patient testing. AB - Automation in near-patient ABO testing has been prohibitive due to cost. Recently, a spectrophotometric approach to blood typing has been developed by examining the spectral slopes of RBC suspensions in saline, in the presence and absence of various antibodies. In this paper, we present a simplified method and a sensor that can replace the spectral imaging component of the diode-array spectrophotometer with a discrete array of LED/IRED and photodiode pairs within the 660nm-1000nm wavelength range of interest. An experimental sensor has been designed and evaluated for the reproduction of results recorded on an HP8453 diode-array spectrophotometer. The LED and photodiode pairs are found to successfully reproduce the spectroscopic determination of red blood cell agglutination, as supported by Mie scattering theory examined herein. PMID- 17282612 TI - A Stereo Thermographic System for Intra-operative Surgery. AB - A stereo far-infrared (FIR) system based on the trigonometric parallax is presented in this paper for locating the distal arterial tree from the coronary artery bypass graft. The system can obtain the wide angle-of-view range information in the near distance by changing the optical path of one fixed uncooled FIR camera. Meanwhile, the speed of pixel movement on the FIR imaging plane is discussed for avoiding the problem on the imaging blur because the images are taken in sequence from a scanning mirror for the real-time monitor of the operation. Besides, the view range is also considered under the different system parameter conditions. After the structure parameters are simulated for evaluating the performance, the optimum system can be designed. This thermal imaging technique is inexpensive, noninvasive and feasible for intra-operative surgery. PMID- 17282613 TI - Automatic DarkAdaptation Threshold Detection Algorithm. AB - This paper describes an algorithm used to automatically determine the threshold sensitivity in a new dark adaptometer. The new instrument is controlled by a personal computer and can be used in the investigation of several retinal diseases. The stimulus field is delivered to the eye through the modified optics of a fundus camera. An automated light stimulus source was developed to operate together with this fundus camera. New control parameters were developed in this instrument to improve the traditional Goldmann-Weekers dark adaptometer. PMID- 17282614 TI - Urine analysis in diluted situation using low-resolution Raman spectroscope. AB - We could get valuable information about various diseases by analyzing urine of patients. For the diabetics, it has been very important to know the glucose concentration in their urine. Until now, there have been many methods to estimate the concentration but they were invasive and annoyed patients. The Low-Resolution Raman Spectroscopy (LRRS) could be an alternative method to be non-invasive and unconscious for patients who want to check the amount of their urine components. LRRS is not expensive and smaller than laboratory Raman spectroscope. And we want to attach it to the common toilet bowl. For the reason, we got the spectrum of diluted urine and predicted the glucose concentration. In addition, we tried to find very small amount of glucose. LRRS was adequate for measuring Raman signal of diluted urine and could find very small amount of glucose. This system will realize the observation of one's health condition every day without awareness. PMID- 17282615 TI - Theoretic discussion on the improvement of the prediction accuracy to noninvasive blood glucose by a new way. AB - The development of near-infrared-based techniques for the noninvasive determination of blood component concentrations has attracted significant interest in recent years. Therefore, the noninvasive measurement of blood compositions has not yet been applied to the clinical field. The most important difficult problems are the effects of the individual discrepancy and other complicated measurement detection. In this article, the dynamic spectrum method, a new method which is based on the principle of photoplethysmography can remove a great deal of the effect of the individual discrepancy and the measurement conditions in detecting blood components, We have discussed its improvement to the prediction accuracy. This will lead to the clinical application of the noninvasive blood component measurement. PMID- 17282616 TI - No invasive Measurement of Urea in Blood Based in Optical Sensing for Hemodialysis Treatments. AB - The present work shows the development of a low-cost system to measure on-line blood urea concentration during dialysis procedures using optical sensor in the visible range. The objective in this project is obtaining the quantification of urea on-line during practices of the hemodialysis treatments. For which it has been considered to be a hypothesis that the dependence in the volume change of the red globules with the urea concentration in the blood is due to the changes to the osmotic pressure and to the mechanisms of regulation of the cellular volume. A bigger concentration of urea would imply a reduction of the volume of the cells and, therefore, a decrease of the optical absorbance. To validate this hypothesis, we used a simplified cellular model based on a yeast cell suspension. Measurements at urea concentrations using a custom single wavelength absorbance meter, and electrical impedance measurements system as contrast technique. Finally to validate this system have carried out thirty mensurations among diverse patient subject a Hemodialysis treatment in the Military Hospital Centre in Mexico, City. PMID- 17282617 TI - A trial of measuring the displacement of tibial fragments with pinless external fixator. AB - Currently, the mechanical performances of pinless external fixator are primarily evaluated for application to long bone fractures. A new method that detecting the relative displacement changes of the tibial fragments with the pinless external fixator by the three dimensional measurement system was introduced to evaluate the performance of the pinless external fixator. And such testing item was taken as the complement for the mechanical performances of the pinless external fixator. In this paper, a high precision optical 3D measurement system was used to detect the displacement change in the anterior and posterior fracture part of the tibial bones which was fixed by a clamp pattern pinless external fixator in open tibial fractures. Furthermore, the relative displacement change and relative angle rotation were analyzed after obtaining the trajectory of the markers which fixed on the tibial fragments, the results were used to evaluate the stability of the pinless external fixator, and taken as the reference for revising the design of the pinless external fixator as well. PMID- 17282618 TI - A new method based on sparse component decomposition to remove MRI artifacts in the continuous EEG recordings. AB - How to effectively remove the Magnetic resonance imaging (MRI) artifacts in the Electroencephalography(EEG) recordings, induced when EEG and Functional magnetic resonance imaging (FMRI) are simultaneously recorded, is a challenge for integration of EEG and FMRI. According to the temporal-spatial difference between MRI artifacts and EEG, a new method based on sparse component decomposition in the mixed over-complete dictionary is proposed in this paper to remove MR artifacts. A mixed over-complete dictionary(MOD) of wavelet and discrete cosine which can exhibit the temporal-spatial discrepancy between MRI artificats and EEG is constructed first, and then the signals are separated by learning in this MOD with Matching pursuit(MP) algorithm. After the sparse decomposition in MOD, the filtered EEG is approximately represented by the linear combination of atoms in the wavelet overcomplete dictionary and the removed MRI artifacts by that in the discrete cosine dictionary. The method is applied to the MRI artifacts corrupted EEG recordings and the decomposition result shows its validation. PMID- 17282619 TI - Computational Neuronal Oscillations using Morlet Wavelet Transform. AB - This paper introduces the use of a new tool based on Morlet wavelet transform to detection the interaction dynamics between two neuronal population oscillations. This toolbox can describe the power spectrum, cross wavelet transform, coherence, bi-coherence, cross phase angle and phase synchronization of two neuronal oscillations. Through a case study of focus epilepsy model, a linear and nonlinear correlation between the neuronal oscillations in the CA1 and CA3 of rat hippocampus are computed. The results show that the tool can be directly applied to analyze and quantify the instantaneous interaction of two neuronal oscillations, which could be a helpful tool to analyze and understand the mechanism of epileptic seizure in EEG recordings. PMID- 17282620 TI - Method for robust spike sorting with overlap decomposition. AB - Spike sorting is the mandatory first step in analyzing multi-unit recording signals for studying information processing mechanisms within the nervous system. Extracellular recordings usually contain overlapped spikes produced by a number of neurons adjacent to the electrode, together with background noise having unknown properties. In the present study, a robust method to deal with these problems is proposed. The method employs an automatic overlap decomposition technique based on the relaxation (RELAX) algorithm that requires simple fast Fourier transforms (FFT's). The performance of the presented system was compared with that of a previously published method and tested at various signal-to-noise ratio (SNR) levels based on synthetic data that were generated from real data. PMID- 17282621 TI - Detecting mental EEG properties using detrended fluctuation analysis. AB - Based on detrended fluctuation analysis (DFA), we explore the characteristics of multichannel electroencephalogram (EEG), which is recorded from many subjects performing different mental tasks. The results show that mental EEG exhibits long range power-law correlations by calculating its scaling exponents (alpha), which can reflect the kinds of mental tasks. The scaling exponent of letter-composing is different from that of multiplication especially at positions C3 and C4, and at positions O1 and O2 the scaling exponent of rotation is also different distinctively from that of multiplication. Detrended fluctuation analysis exhibits its robustness against noises in our works. We could benefit more from the results of this paper in designing mental tasks and selecting brain areas in brain-computer interface systems. PMID- 17282622 TI - Blind estimation of evoked potentials in alpha stable distribution environments. AB - Evoked potentials (EPs) have been widely used to quantify neurological system properties. Traditional EP analyses are developed under the condition that the background noise in EP analysis are Gaussian distributed. Alpha stable distribution, a generalization of Gaussian, is better for modeling impulsive noise than Gaussian distribution in biomedical signal processing. Conventional blind separation and estimation method of evoked potentials is based on second order statistics (SOS). In this paper, we modify our conventional algorithms and analyze the stability and convergence performance s of the new algorithm. The simulation experiments show that the proposed algorithm based on fractional lower order statistics is more robust than the conventional algorithm based on second order statistics. PMID- 17282623 TI - Structural complexity of neural signals by matching pursuits. AB - Matching pursuits (MP) based adaptive approximation represents a signal with linear combination of a group of atom functions, which is closely related to the structural characteristics of the corresponding signal. In this study, we propose to use the average atom density (AAD) and the average atom scale (AAS) to evaluate the structural complexity of neural signals. For a simulated dynamic model, logistic map, both measurements behave similarly to the Lyapunov exponent spectrum. We apply them to the analysis of neural signal, namely EEG, from the brain with hypoxicischemic (HI) injury. The results show that AAD and AAS decrease in the early stage of the HI injury recovery because of the bursting and spiky activities. The preliminary results imply that the AAD and AAS can be used to describe the structural complexity changes in the neural signals, and can be used to segment the stages of HI injury and its recovery. PMID- 17282624 TI - Single-trial extraction of cognitive evoked potentials by combination of third order correlation and wavelet denoising. AB - The application of a recently proposed denoising implementation for obtaining cognitive evoked potentials (CEPs) at the single-trial level is shown. The aim of this investigation is to develop the technique of extracting CEPs by combining both the third-order correlation and the wavelet denoising methods. First, the noisy CEPs was passed through a finite impulse response filter whose impulse response is matched with the shape of the noise-free signal. It was shown that it is possible to estimate the filter impulse response on basis of a select third order correlation slice (TOCS) of the input noisy CEPs. Second, the output from the third-order correlation filter is decomposed with bi-orthogonal splines at 5 levels. The CEPs is reconstructed by wavelet final approximation a5. We study its performance in simulated data as well as in cognitive evoked potentials of normal rat and Alzheimer's disease (AD) model rat. For the simulated data, the method gives a significantly better reconstruction of the single-trial cognitive evoked potentials responses in comparison with the simulated data. Moreover, with this approach we obtain a significantly better estimation of the amplitudes and latencies of the simulated CEPs. For the real data, the method clearly improves the visualization of single-trial CEPs. This allows the calculation of better averages as well as the study of systematic or unsystematic variations between trials. PMID- 17282626 TI - Transient phase synchrony of independent cognitive components underlying scalp EEG. AB - Dynamic synchronization between different brain regions has long been considered as the underlying neural mechanism of sensory, motor and cognitive functions. Practical methods of accurately quantifying this kind of dynamics by using scalp EEG are plagued by volume conduction effects and background noise. We propose a new method of measuring transient phase locking between independent components underlying cognitive brain activities. This unique combination of independent component analysis (ICA) and phase locking statistics (PLS) provides a promising technique for investigating the dynamics of neural synchronization between different cortical regions, without the contamination of background coherence. This method was tested on the EEG from a cross-modal working memory experiment and its efficacy in detecting transient phase synchrony was demonstrated. PMID- 17282625 TI - Measuring coupling asymmetry and time delays in neural oscillators. AB - We address an important problem in neurophysiology concerning the characterization of coupled neural oscillators from experimental data. The approach employs the formal mathematical description of the dynamics of weakly coupled oscillators by the phase model, and the recently developed methods for identification of directionality of coupling and estimation of coupling delays. We study neuron oscillator models with synaptic coupling and diffusively coupled ensembles of neurons, incorporating time delays in coupling. Results of directionality analysis closely reflect the coupling strength asymmetry. In comparison with the standard crosscorrelation analysis, the phase dynamics based time delays estimation provides more accurate estimates of coupling delays. PMID- 17282627 TI - EEG-Based Mental Task Classification in Hypnotized and Normal Subjects. AB - EEG-Based mental task classification is an approach to understand the processes in our brain which lead to our thoughts and behavior. Different mental tasks have been used for this purpose and we have chosen relaxation and imagination for our study. As well as normal conscious state, we have considered mental tasks performed in hypnosis which is defined as a state of consciousness with high concentration. To assess nonlinear dynamics, we have considered fractal dimension in addition to frequency features. HMM classifiers have been used for classification. Results show the most important features in EEG signal related to mentioned mental tasks as well as differences between normal and hypnotic states of the brain. PMID- 17282628 TI - Key Feature Extraction for Fatigue Identification using Random Forests. AB - Electroencephalogram (EEG) might be the most predictive and reliable physiological indicator of mental fatigue. However, the extraction of key features from massive EEG data for mental fatigue identification remains a challenge. The objective of this study is to identify the key EEG features in relationship to mental fatigue, from a broad pool of EEG features generated by quantitative EEG (qEEG) techniques, using Random Forests (RF), which is a recently developed machine learning algorithm. The method is applied to key EEG feature extraction for 5-level mental fatigue identification using the five subjects' EEG data recorded in 25-hour fatigue experiments. RF produces significant feature reduction with little compromise of the classification performance. The identified key EEG features also indicate that electrode locations in frontal and occipital regions of the brain are most important for adequate representation of the deactivation of functional lobes of the brain, which is consistent with the anatomical areas known to be involved in mental fatigue. It is also interesting to discover that the four frequency bands are all important for the mental fatigue identification. PMID- 17282629 TI - A novel neural network with Non-Recursive IIR Filters on EEG Artifacts Elimination. AB - The artifacts caused by various factors, EOG (electrooculogram), blink and EMG (electromyogram), in EEG (Electroencephalogram) signals increase the difficulty in analyzing them. In addition, EEG signals containing artifacts often cannot be used in analyzing them. So, it is useful and indispensable to eliminate the artifacts from EEG signals. In this paper, a neural network with non-recursive IIR (Infinite Impulse Response) filters are used to eliminate the artifacts from EEG signals. The proposed method is a new approach that is respect to slotting a non-recursive IIR filter into individual neurons of a neural network. First of all, in order to investigate the usefulness of the proposed method in eliminating the artifacts from EEG signals, we apply it to the artificial EEG signals that are weakly stationary process. As the result, the artifacts can be eliminated from EEG signals almost exactly using the proposed method, and it is suggested the proposed method should be useful in eliminating the artifacts from EEG signals. PMID- 17282630 TI - Single-trial estimation of imitating-natural-reading evoked potentials in single channel. AB - Using Imitating-Natural-Reading Induced Potentials as communication carriers, we are constructing a Brain-computer interface based mental speller which enable users to interaction with computers. The potentials were induced in this way: In a trial, strings consisted of target and non-target symbols were moving smoothly from right to left through a little visual window at the center of computer screen. Subject was instructed to stare at the visual window to count the target, and thus potentials were evoked. In practical applications, fewer electroencephalograph recording channels are preferred. We explored the single trial estimating of event-related potentials recorded in single-channel using support vector machines in three subjects. With carefully feature selections, we obtained satisfying results of correct classification rate, which is 92.1%, 94.1% and 91.5%, respectively. The results demonstrated the advantages of the inducing paradigm used in our experiments. PMID- 17282631 TI - Wavelet analysis of ischemia and reperfusion injury models. AB - Fourier transform of electroencephalography (EEG) restricts EEG analysis due to its stationary properties with time change. It makes analysis difficult to ascertain the global effects of transient change in ischemia and reperfusion model. This study examines that multi-resolution analysis distinguishes different depths of ischemic insult related to the degree of residual blood flow in animal models. The results suggest that multi-resolution analysis demonstrate that little blood flowing to the brain has more detrimental effect to the EEG properties than no blood flowing, which is contrary to the common sense. PMID- 17282632 TI - Image Cytometry Data From Breast Lesions Analyzed using Hybrid Networks. AB - The treatment and therapy to be administered on breast cancer patients are dependent on the stage of the disease at time of diagnosis. It is therefore crucial to determine the stage at the earliest time possible. Tumor dissemination to axillary lymph nodes has been regarded as an indication of tumor aggression, thus the stage of the disease. Neural networks have been employed in many applications including breast cancer prognosis. The performance of the networks have often been quoted based on accuracy and mean squared error. In this paper, the performance of hybrid networks based on Multilayer Perceptron and Radial Basis Function networks to predict axillary lymph node involvement have been investigated. A measurement of how confident the networks are with respect to the results produced is also proposed. The input layer of the networks include four image cytometry features extracted from fine needle aspiration of breast lesions. The highest accuracy achieved by the hybrid networks was 69% only. However, most of the correctly predicted cases had a high confidence level. PMID- 17282633 TI - Hands-free Head-movement Gesture Recognition using Artificial Neural Networks and the Magnified Gradient Function. AB - This paper presents a hands-free head-movement gesture classification system using a Neural Network employing the Magnified Gradient Function (MGF) algorithm. The MGF increases the rate of convergence by magnifying the first order derivative of the activation function, whilst guaranteeing convergence. The MGF is tested on able-bodied and disabled users to measure its accuracy and performance. It is shown that for able-bodied users, a classification improvement from 98.25% to 99.85% is made, and 92.08% to 97.50% for disabled users. PMID- 17282634 TI - Tracking Epileptiform Activity in the Multichannel Ictal EEG using Spatially Constrained Independent Component Analysis. AB - Blind source separation (BSS) methods such as independent component analysis (ICA) are increasingly being used in biomedical signal processing for decomposition of multivariate time-series, such as the multichannel electroencephalogram (EEG), into a set of underlying sources, some of which may reflect clinically relevant neurophysiological activity such as epileptic seizures or spikes. Tracking and detecting signals of interest fundamentally requires at least some a priori knowledge or assumptions regarding the spatial and/or temporal characteristics of the target sources. While such prior information is conventionally used during post-processing, it seems equally sensible to incorporate any available information into the data decomposition process from the outset. This work presents an alternative approach to source tracking in multichannel EEG, which exploits prior knowledge of the spatial topographies of the scalp voltage distributions associated with the target sources. The predetermined target topographies are used in conjunction with spatially constrained ICA to extract target source waveforms which are uncontaminated by contributions from coactive and spatially correlated brain and artifact sources. These signals can then be further analyzed in terms of their morphological, spectral or statistical properties. As illustrated in the context of epileptiform EEG, this method is useful for tracking seizures. PMID- 17282635 TI - Decomposition of Evoked Potentials using Peak Detection and the Discrete Wavelet Transform. AB - A new method of viewing evoked potential data is described. This method, called the peak detection method, is based on singularity detection using the Discrete Wavelet Transform. The peaks and troughs of raw Visual Evoked Potential data are identified and characterized using the algorithms of this method, resulting in a linear decomposition of the recording into sets of individual peaks. The individual peaks are then added together, averaged and compared to the ensemble average signal. The peak detection method correlates strongly to the ensemble average showing that this method retains the same evoked potential signal profile. PMID- 17282636 TI - Latency Reduction during Telemetry Transmission in Brain-Machine Interfaces. AB - Advanced array processing techniques are becoming an indispensable requirement for integrating the rapid developments in wireless high-density electronic interfaces to the central nervous system with computational neuroscience. This work aims at describing a systems approach for latency reduction in telemetry linked brain machine interfaces to enable real-time transmission of high volumes of neural data. We show that the tradeoff between transmission bit rate and processing complexity requires a smart processing mechanism to strip the redundancy and extract the useful information early in the data stream. The results presented demonstrate that space-time processing offers tremendous savings in communication costs compared to on-chip spike detection followed by off-chip classification. They also demonstrate that the performance asymptotically approaches that of on-chip spike detection and sorting. Detailed performance evaluation is described. PMID- 17282637 TI - Influence of inter-stimulus interval on auditory evoked potentials. AB - In this research, the influence of the preceding auditor stimulus on the auditory evoked potential (AEP) of the succeeding stimuli was investigated, when the human subjects were presented with a pair of auditory stimuli. We found that the evoked potential of the succeeding stimulus was inhibited completely by the preceding stimulus, when the inter-stimulus interval (ISI) was shorter than 150 ms. The influence was depended on the ISI of two stimuli, the longer was the ISI, the stronger would be the influence. The inhibitory influence by the preceding stimulus might be caused by the neural refractory effect. PMID- 17282638 TI - Mismatch Negativity to Different Time-frequency Distribution Complex Tones. AB - This study aims to determine whether or not the mismatch negativity (MMN) is involved in the processing on time-frequency distribution of acoustic information. Invariable, step down and gradually decreasing time-frequency distribution complex tones compose the three kinds of deviant stimuli, which appear randomly in the repeating standard tones sequence. MMNs were evoked by the deviant stimuli. The data indicate that the latency, onset and duration of elicited MMN were different among the deviant stimuli. The results suggest that MMN is sensitive to the time-frequency distribution feature. The rapid changes in the stimulus may affect the duration of MMN significantly. Such rapid change detection capability reflected by MMN may be related to the highly rapid sound information processing in human auditory system. PMID- 17282640 TI - Desynchronization network analysis for the recognition of imagined movement. AB - This paper reports on the use of electroencephalogram (EEG)-based phase desynchronization networks for the recognition of imagined movements. Features derived solely from these networks are classified using linear support vector machine. An average accuracy of 73% is achieved for the single-trial imagined hand versus foot movements. The results demonstrate that phase desynchronizations provide relevant information for the discrimination of mental tasks. This novel approach will potentially benefit the development of brain-computer interfaces. PMID- 17282639 TI - A filter based encoding model for mouse retinal ganglion cells. AB - We adopt a system theoretic approach and explore the model of retinal ganglion cells as linear filters followed by a maximum-likelihood Bayesian predictor. We evaluate the model by using cross-validation, i.e., first the model parameters are estimated using a training set, and then the prediction error is computed (by comparing the stochastic rate predicted by the model with the rate code of the response) for a test set. As in system identification theory, we present spatially uniform stimuli to the retina, whose temporal intensity is drawn independently from a Gaussian distribution, and we simultaneously record the spike trains from multiple neurons. The optimal linear filter for each cell is obtained by maximizing the mutual information between the filtered stimulus values and the output of the cell (as measured in terms of a stochastic rate code). Our results show that the model presented in this paper performs well on the test set, and it outperforms the identity Bayesian model and the traditional linear model. Moreover, in order to reduce the number of optimal filters needed for prediction, we cluster the cells based on the filters' shapes, and use the cluster consensus filters to predict the firing rates of all neurons in the same class. We obtain almost the same performance with these cluster filters. These results provide hope that filter-based retinal prosthetics might be an effective and feasible idea. PMID- 17282641 TI - Non-Poisson Fluctuation Statistics In Neuronal Inter-Spike Intervals (ISI): Hurst parameter Estimates of Mouse Retinal Ganglion Signals. AB - There is considerable recent interest in both (i) modelling the retinal ganglion cells, so that the models can generate output that approximates the actual response of the retina (such models will help design retinal prosthetics); and (ii) understanding how relevant information is encoded in the spike patterns generated by the ganglion cells (these neuronal codes will help understand how the brain analyzes visual scenes). Since the signals (as captured by ISI) are fundamentally stochastic, any modelling or analysis tool will have to track, and make assumptions about, the fluctuations or noise inherently present in these signals. Even though there have been recent work claiming that the fluctuations are fractal in nature, showing long-range dependencies, almost all modelling and analysis work continue to assume Poisson fluctuations. The widespread use of the Poisson model is partly for the sake of convenience, and partly due to the fact that those claiming on fractal nature of ISI are contradictory: In [1] a long range dependency (i.e., Hurst parameter [2], H > 0.5) is claimed in cat's retina, and in [3] an H < 0.5 and a long-range anti-correlation are claimed for paddlefish electroreceptors. We resolve this issue by studying the ISI of more than 50 ganglion cells recorded from two different mouse retinas, and (i) Conclusively show that the Hurst parameter is less than 0.5; we also show why the results presented in [1] are erroneous: methods that do not detrend the data were used. PMID- 17282642 TI - The characteristics of event related potential in the cognitive course of individual Chinese characters. AB - The difference between the Chinese and English character recognition process and the characteristics of Chinese character recognition process are investigated by analyzing the ERP difference between the matched and mismatched ending strokes of a single Chinese character. First, the P300 are observed in the mismatched ERP waveforms, which don't exist in the matched ERP waveforms (P<0.05). These phenomena demonstrate that the recognition of the pictograph Chinese characters are not only affected by the semanteme, but also closely related to its image of the figure. Secondly, the amplitude of the N400 in the mismatched ending strokes of Chinese character is obviously higher than that in the matched groups (P<0.05). The N400 is distributed in the other areas except the right side of temporal lobe and is higher in the left side. However, the amplitude of N400 in the waveforms has no obvious distinction between the cerebral hemispheres, where the amplitude of N400 are obtained by distracting the ERP of the mismatched individual Chinese character by the ERP of the matched group. These results show that the difference between cerebral hemispheres is attributed to the formal and phonic processing, not due to the semantic processing, which verify that the left and right cerebral hemisphere are both used in the Chinese character recognition, which is very different from the English character recognition, where the left side cerebral hemisphere is used with high percentage. PMID- 17282643 TI - Chaotic Synchronization of Multi-neurons in External Electrical Stimulation. AB - The synchronization of n(n≥3) neurons coupled with gap junction in external electrical stimulation is investigated. In this paper, the coupled model is established on the basis of nonlinear cable model, and then the relation of coupling strength of the gap junction and the synchronization is discussed in detail. The sufficient condition of complete synchronization is attained from rigorously mathematical derivation. The synchronizations of periodic neurons and chaotic neurons are studied respectively. PMID- 17282644 TI - Recognition of Chewing Behavior from Electroencephalogram Recorded in the Rat's Nucleus Accumbens. AB - Nucleus accumbens is used to be considered as the interface to motor nerve system. In this paper, our object is to study the relationship between the electro-activity of neurons in nucleus accumbens and the rat-behavior. We recorded neurons action potentials with multichannel microelectrodes, which were chronically implanted in a rat's nucleus accumbens, during rats-chewing behavior. Through digital signal processing, we found significant features associated with the chewing activity and we could recognize the chewing behavior easily from the electroencephalogram with these features. This study suggests that neurons action potentials in a nucleus accumbens are activated by specific animal actions. PMID- 17282645 TI - Information capacity of brain machine interfaces. AB - Brain Machine Interfaces (BMIs) are emerging as an important research area in clinical therapy. A large range of potential BMI control signals can be found in the brain. In increasing order of volume of brain tissue being sampled, these signal includes recordings of electric discharges from multi unit activity (MUA), summed population activity of thousands of neurons via local field potentials (LFPs), and electrical activity recorded from either the surface of the brain via electrocorticograms (ECoGs) or the surface of the scalp via electroencephalograms (EEGs). While each of these signals have been studied separately, it has been difficult to compare the potential that each signal has for general prosthetic control across studies. Information theory has been proposed as an abstract measurement to bridge this gap, however the maximum information rates of any experiment is limited by the parameters defined by that experiment (e.g. inter trial interval length, number of targets). Here we propose a different measure of information, which we call information capacity, which measures the maximum possible information rate that a signal can provide. An advantage of measuring information capacity is that it can readily be compared between different signals and different tasks. We show how to calculate information capacity making linear Gaussian assumptions, and we discuss more general possibilities. We present a case study involving a rat BMI task involving either MUA or LFP signals. PMID- 17282646 TI - Learning-induced Dependence of Neuronal Activity in Primary Motor Cortex on Motor Task Condition. AB - A brain-computer interface (BCI) system such as a cortically controlled robotic arm must have a capacity of adjusting its function to a specific environmental condition. We studied this capacity in non-human primates based on chronic multi electrode recording from the primary motor cortex of a monkey during the animal's performance of a center-out 3D reaching task and adaptation to external force perturbations. The main condition-related feature of motor cortical activity observed before the onset of force perturbation was a phasic raise of activity immediately before the perturbation onset. This feature was observed during a series of perturbation trials, but were absent under no perturbations. After adaptation has been completed, it usually was taking the subject only one trial to recognize a change in the condition to switch the neuronal activity accordingly. These condition-dependent features of neuronal activity can be used by a BCI for recognizing a change in the environmental condition and making corresponding adjustments, which requires that the BCI-based control system possess such advanced properties of the neural motor control system as capacity to learn and adapt. PMID- 17282647 TI - A Comparison of Time, Frequency and ICA Based Features and Five Classifiers for Wrist Movement Classification in EEG Signals. AB - This study presents a comparison of two methods to extract features for the classification of wrist movements (flexion, extension, pronation, supination). For the first method, a set of 160 features was extracted from the filtered time and frequency domain EEG data and its alpha, beta, and theta bands. For the second method, a set of 40 features per movement type was extracted from the ICA calculated source signals. The value of the Davies-Bouldin cluster separation index for each feature was used for selecting the best five features from each set so as to avoid the subjective selection or rejection of any of the features. Finally, five different kinds of classifiers were chosen to obtain classification error rates with which to compare both techniques. The results showed the advantage of using ICA source signals for wrist movement classification purposes, at least as compared to the simple time and frequency domain features. Left and right movements were correctly identified with accuracies ranging from 70% to 96%. However, the methodology presented here did not succeed in distinguishing the subclasses (e.g., flexion versus extension) with accuracy above 70%. This suggests that additional work is needed to explore different features as well as classifiers. PMID- 17282648 TI - Real-time Detection of Unitary Events For Cortical Control. AB - Traditional brain-machine interfaces have typically focused on methods that use rate-based codes as a source for control signals. Opposed to rate, timing of firing across different neurons and within each neuron could also provide information that can be used for controlling brain-machine interfaces or neuroprosthetic devices. Findings have indicated that synchronization of individual spike discharges may help serve the organization of cortical motor processes. We are investigating neural firing synchrony in the context of using it for real-time control for neuroprostheses systems. Our results with rats suggest that subjects can be trained to synchronize neural firing and increase unitary events i.e. spike coincidence patterns that are significantly above chance. Temporal coding methods could be used as additional or alternative cortical control signals for neuroprostheses and brain machine interfaces. PMID- 17282649 TI - Anteroventral cochlear nucleus models for considering on the missing fundamental. AB - Several phenomena, which were made clear by psycho-acoustic experiments, have not electric physiologic evidence data. The missing fundamental phenomenon is one of the phenomena. We try making clear the mechanism how the missing fundamental is produced. By psycho-acoustic experiments and Cochlear models experiments, we investigated its fundamental characteristics in the low frequency range where the influence of spontaneous discharge of primary auditory nerves and the influence of refractory period of primary auditory nerves can be ignored. In order to investigate the mechanism of the missing fundamental in the frequency range where these influence can not be ignored, we have made Anteroventral Cochlear Nucleus models (AVCN models). In this report, Cochlear models - AVCN models is mentioned. And it is also mentioned that the frequency information of the missing fundamental of input signals lower than 900Hz explicitly appeared in the interspike-interval histogram of the aggregated autocorrelogram of output pulse trains from Cochlear models - AVCN models. To confirm it by the perceptual experiments, psycho-acoustic experiments will be carried out in the future. PMID- 17282650 TI - Motor cortical decoding using an autoregressive moving average model. AB - We develop an Autoregressive Moving Average (ARMA) model for decoding hand motion from neural firing data and provide a simple method for estimating the parameters of the model. Results show that this method produces more accurate reconstructions of hand position than the previous Kalman filter and linear regression methods. The ARMA model combines the best properties of both these methods, producing reconstructed hand trajectories that are smooth and accurate. This simple technique is computationally efficient making it appropriate for real time prosthetic control tasks. PMID- 17282652 TI - Remote heart sound monitoring system. AB - A kind of remote monitoring system on heart sound is constructed, which can tele monitor ECG and PCG. The system integrates embedded internet technology and wireless technology. As it can send ECG and PCG by internet, it realizes real time recording and monitoring of physiology parameter of patients at low cost and both at home and in hospital, and it also can be used for analysis for computer or reference for doctor. This study demonstrated that such kind of tele monitoring system provides a low-cost, reliable and convenient solution for data acquisition and analysis of the PCG. PMID- 17282653 TI - Research on the microcapsule production by high voltage pulsing method. AB - This paper adopt the high voltage pulsing microcapsule shaping device to produce microcapsules. Through processing the experiment on microcapsule production by changing the voltage, frequency, pulse width and pushing velocity, we could get the parameters related with the controlling of the diameter, shape and homogeneous degree. It is concluded that the size of microcapsules is mainly influenced by the voltage. The diameter of microcapsules decreases as the voltage increases. The homogeneous degree is largely influenced by the frequency. The homogeneous degree turns to be better when the frequency increases. The diameter and homogeneous degree of the microcapsules are also influence by the pulse width that should not be too large, a quarter to one half of the cycle will be the best. PMID- 17282651 TI - Synchronized spontaneous spikes on multi-electrode array show development of cultured neuronal network. AB - Spontaneous firing play an important role in development of neuronal network. Activity-dependent modification of synaptic efficacy is widely recognized as a cellular basis of learning, memory, and development plasticity. Little is known of the activity-dependent modification of the synchronized spontaneous firing of the hippocampal networks. Long-term recording of spontaneous activity in cultured hippocampal neuronal networks was carried out using substrates containing multi electrode array (MEA). Spontaneous uncorrelated firing appeared within a week and transformed progressively into synchronized pattern. During the development, these synchronized firings became into oscillation pattern and the synchronization has little change. By paired stimulation from adjacent electrodes in the network, the synchronized firing form a larger network burst. These results suggest that synchronized spontaneous spikes show the development of neuronal network and electronical stimulation could change the development. PMID- 17282654 TI - EasiMed: A remote health care solution. AB - An embedded remote health care system based on wireless sensor network technology was established. Firstly, a new system architecture was proposed which introduced a scalable wireless personal medical sensor network around human's body. Then the designs of several sensor node and the care base-station were presented. The wireless communication between the sensor nodes and the care base-station used IEEE 802.15.4/Zigbee standard whilst the care base-station and the remote central server was connected in one of the following ways, including computing network, GSM short messages and telephone modem. The system can be used for remote health care at home or in the hospitals. PMID- 17282655 TI - Healthcare services towards individualised wellness (i-wellness). AB - Information technology applications in medicine are rapidly expanding, and new methods and solutions are evolving since they are considered pivotal in the success of preventive medicine. In this paper two different concepts will be presented, the PANACEIA-iTV and the e-Vital concept. PANACEIA-iTV is a home care service provision system based on interactive TV technology and supported by the IST programme of the European Commission. The e-Vital service, supported by the eTEN programme of the European Commission, regards an integrated homecare and telemonitoring service chain aimed at large sensitive parts of the European population, the "at-risk" citizens. Both concepts developed a generic, flexible and adaptable framework for the combination of heterogeneous information sources and the creation of the individualised wellness (i-wellness) profile for prognostic purposes and early intervention. PMID- 17282656 TI - Virtual Reality-based Telesurgery via Teleprogramming Scheme Combined with Semi autonomous Control. AB - Telesurgery systems have long been suffering variable and unpredictable Internet commutation time delay, operation fatigue, and other drawbacks. Based on virtual reality technology, a teleprogramming scheme combined with semi-autonomous control is introduced to guarantee the robustness and efficiency of teleoperation of HIT-RAOS, a robot-assisted orthopedic surgery system. In this system, without considering time delay, the operator can just interact with virtual environment which provides real-time 3D vision, stereophonic sound, and tactile and force feedback imitated by a parallel master manipulator. And several tasks can be managed simultaneously via semi-autonomous control. Finally, the method is experimentally demonstrated on an experiment of locking of intramedullary nails, and is shown to effectively provide stability and performances. PMID- 17282657 TI - The Development of a Remote Patient Monitoring System using Java-enabled Mobile Phones. AB - A remote patient monitoring system is described. This system is to monitor information of multiple patients in ICU/CCU via 3G mobile phones. Conventionally, various patient information, such as vital signs, is collected and stored on patient information systems. In proposed system, the patient information is recollected by remote information server, and transported to mobile phones. The server is worked as a gateway between hospital intranet and public networks. Provided information from the server consists of graphs and text data. Doctors can browse patient's information on their mobile phones via the server. A custom Java application software is used to browse these data. In this study, the information server and Java application are developed, and communication between the server and mobile phone in model environment is confirmed. To apply this system to practical products of patient information systems is future work. PMID- 17282658 TI - A flexible measurement system for physiological signals in mobile health care. AB - In the nearest future a lot of post-operative treatment and health monitoring is going to be performed in people's homes instead of in hospital. The increasing number of elderly people in the developed countries and the need for more advanced medical treatment and equipment in conjunction with economical demands will force the development of more cost-effective solutions. The equipment used must be very rugged and safe for both the patient and the operator and easily configured for a number of different measurement parameters. In most cases storing data on a memory card in the equipment will be sufficient but sometimes a wireless real-time measurement system is needed. This paper presents an acquisition system flexible enough for a number of different applications, home care, mobile health care and other biomedical measurement situations. A prototype system has been tested with sufficient performance for several physiological signals. PMID- 17282659 TI - 3G Networks in Emergency Telemedicine - An In-Depth Evaluation & Analysis. AB - The evolution of telecommunications technologies in connection with the robustness and the fidelity these new systems provide, have opened up many new horizons as regards the provision of healthcare and the quality of service from the side of the experts to that of the patients. The purpose of this paper is to evaluate the third generation telecommunications systems that are only recently being deployed in Europe, as well as argue on why a transition from 2G and 2.5G to 3G telecommunications systems could prove to be crucial, especially in relation to emergency telemedicine. The experimental results of the use of these systems are analyzed, the implementation of a tele-consultation unit is presented and their exploitation capabilities are explored. PMID- 17282660 TI - Robotic telementoring/telesurgical system and randomized evaluation study. AB - The paper presents a new telementoring system incorporating audio-video communication and remote robotic control. The system was developed around an off the shelf ISDN video conferencing system enhanced with video annotation and remote robot control features. The user can remotely control a robot of perform needle alignment and insertion in a Percutaneous access procedure. Particular attention was devoted to ensure the safety of the procedure. The data connection is continuously monitored and in the event of a failure the robot control is switched to the local operator. Two series of randomized trials were performed between Baltimore and London. The accuracy and procedure time were evaluated for manual needle placement, local robotic needle placement and remotely controlled robotic needle placement. The test showed that while the procedure time is not improved by the robotic approach there is an improvement in the accuracy of the procedure. The study showed also that there is no significant difference between the locally controlled robotic needled placement and the remotely controlled robotic needle placement. Thus, the proposed system can be safely used for remote robotic percutaneous access procedures. PMID- 17282661 TI - A methodology to monitor the changing trends in health status of an elderly person by developing a markov model. AB - In this paper we are proposing a statistical testing methodology to monitor changing trends in the health status of elderly people. The occupancy pattern of elderly people can be modeled using a Markov chain, estimating transition probabilities of the chain and test hypotheses about them. The profile of the person for a given period can be stored as a transition matrix of a discrete, regular, ergodic Markov chain. The observation of the occupancy pattern for a given test period can be established as a test Markov chain using information from sensors such as infrared sensors, magnetic switches etc. In the absence of real time data, we have used uniformly distributed transition probabilities to define the profile of the Markov chain and then generated test Markov chain based on this model. The transition probabilities are extracted for the test and profile Markov chain using Maximum Likelihood Estimates (MLE). The statistical testing of occupancy monitoring establishes a basis for statistical inference about the system performance without generating any real time statistics for the occupancy pattern. Chi square test and likelihood ratio tests ensure that the sequences generated from the two Markov chains are statistically same. Any difference in profile Markov chain and test Markov chain could indicate a changed health status of the elderly person. PMID- 17282662 TI - Performance Evaluation of Telemedicine System based on multicasting over Heterogeneous Network. AB - For appropriate diagnosis, medical image such as high quality image of patient's affected part and vital signal, patient information, and teleconferencing data for communication between specialists will be transmitted. After connecting patient and specialist the center, sender acquires patient data and transmits to the center through TCP/IP protocol. Data that is transmitted to center is retransmitted to each specialist side that accomplish connection after being copied according to listener's number from transmission buffer. At transmission of medical information data in network, transmission delay and loss occur by the change of buffer size, packet size, number of user and kind of networks. As there lies the biggest delay possibility in ADSL, buffer Size should be established by 1Mbytes first to minimize transmission regionalism and each packet's size must be set accordingly to MTU Size in order to improve network efficiency by maximum. Also, listener's number should be limited by less than 6 people. Data transmission consisted smoothly all in experiment result in common use network- ADSL, VDSL, WLAN, LAN-. But, possibility of delay appeared most greatly in ADSL that has the most confined bandwidth. To minimize the possibility of delay, some adjustment is needed such as buffer size, number of receiver, packet size. PMID- 17282663 TI - Optimum design for teleconsultation systems. AB - We analyse the clinical process of patient referral developed and in routine use for over 5 year at Chorleywood Health Centre, UK. The system combines diagnostics performed in primary care with results forwarded to the consultant in electronic form. Patients may then be referred for teleconsultation between patient and local health care professional and distant consultant. By ensuring diagnostic information is gained in advance, we have determined that the teleconsultation may concentrate on management, and as a result is more efficient and effective. We further analyse the processes and determine the functional characteristics of the teleconsultation and the functional requirements of the teleconsultation system that may support the process in an optimum way. PMID- 17282664 TI - Online collaboration environments in telemedicine applications of speech therapy. AB - The use of telemedicine in speech and language pathology provides patients in rural and remote areas with access to quality rehabilitation services that are sufficient, accessible, and user-friendly leading to new possibilities in comprehensive and long-term, cost-effective diagnosis and therapy. This paper discusses the use of online collaboration environments for various telemedicine applications of speech therapy which include online group speech therapy scenarios, multidisciplinary clinical consulting team, and online mentoring and continuing education. PMID- 17282665 TI - Design and Application of Embedded System Based on ARM7 LPC2104 Processor in Telemedicine. AB - This paper, based on ARM7 processor and real-time embedded operating system (μC/OS-II), establishes an embedded telemedicine platform ground on LPC2104 and realizes some very popular embedded application technologies such as USB communication, embedded Internet communication, infrared communication, etc. Meanwhile the volume of the hardware is smaller; power consumption is lower; the functions are mightier and the expansibility is stronger. In addition, for the embedded real-time μC/OS-II in use has gone through the reliability authentication, the whole running system is more stable and the program maintenance and update is more convenient. The telemedicine system based on this technology has been tested to be stable and efficient, and has obtained the results as expected. PMID- 17282666 TI - Applying Telemedicine to Remote and Rural Underserved Regions in Brazil using eMedical Consulting Tool. AB - In this paper, we are going to depict a medical tele-consultation network for medical imaging that has been deployed in Brazil. Preliminary outcomes of the medical network will be presented. In addition, the medical application used for tele-consultations will be shown. Eighty nine ultrasound acquisitions took place in the period of five months of the operation of the medical network and five hundred fifty six medical consultations performed. PMID- 17282667 TI - The development and application of the telemedicine system in psychiatric counseling. AB - Telemedicine are the application and development of the telecommunication networks. In this study, we try to develop the telemedicine system and to discuss the network application of this system in psychiatric counseling. The preliminary result of this study is that the telemedicine system is more effective than traditional consultation and it can provide teleconsultation service for clients with depression through the internet. PMID- 17282668 TI - TEIN-based Teledermatological Service System among Korea, China and Austria. AB - A teledermatological service system among Korea, China and Austria has been developed and tested in this research. For successful design and establishment of a teledermatological service system, four elements were considered - networking among hospitals and participants, standard specification for teledermatological consultation, database for medical record, and design and implementation of software. In addition to the fundamental stationary system, mobile teledermatological service function using PDA was added to provide dermatologists with ubiquitous consultation service. It was evaluated and proved to be a feasible for teleconsultation system by the dermatologists participated in this research. PMID- 17282669 TI - A Wireless Physiological Signal Monitoring System with Integrated Bluetooth and WiFi Technologies. AB - This paper proposes a wireless patient monitoring system which integrates Bluetooth and WiFi wireless technologies. A wireless portable multi-parameter device was designated to acquire physiological signals and transmit them to a local server via Bluetooth wireless technology. Four kinds of monitor units were designed to communicate via the WiFi wireless technology, including a local monitor unit, a control center, mobile devices (personal digital assistant; PDA), and a web page. The use of various monitor units is intending to meet different medical requirements for different medical personnel. This system was demonstrated to promote the mobility and flexibility for both the patients and the medical personnel, which further improves the quality of health care. PMID- 17282670 TI - A Communication Platform for Tele-monitoring and Tele-management of Type 1 Diabetes. AB - Type 1 diabetes mellitus is a chronic disease characterized by blood glucose levels out of normal range due to inability of insulin production. This dysfunction leads to many short- and long-term complications. In this paper, a system for tele-monitoring and tele-management of Type 1 diabetes patients is proposed, aiming at reducing the risk of diabetes complications and improving quality of life. The system integrates Wireless Personal Area Networks (WPAN), mobile infrastructure, and Internet technology along with commercially available and novel glucose measurement devices, advanced modeling techniques, and tools for the intelligent processing of the available diabetes patients information. The integration of the above technologies enables intensive monitoring of blood glucose levels, treatment optimisation, continuous medical care, and improvement of quality of life for Type 1 diabetes patients, without restrictions in everyday life activities. PMID- 17282671 TI - Interactive Information Environment for the controlled practice of physical training to improve cardiovascular fitness. AB - Physical inactivity is one of the risk factors of Coronary heart disease. Physical activity protects against the development of CVD and also favorably modifies other risk factors, however a huge part of the population lead a relatively sedentary lifestyle. Virtual Trainer (VT) Concept is a technological platform for the controlled practice of physical training to achieve better cardiovascular fitness results that includes a motivational environment crated to support the long term compliance with the training program. VT consist of a technological platform, a method for the fitness condition assessment and the motivational multimedia environment. This paper describes the firsts results achieved in the project on the technological platform and the fitness condition assessment. PMID- 17282672 TI - Implementation of Measuring Bio-signals Simultaneously using Time-Sharing Method. AB - In this paper, we propose a measuring device implementation to measure ECG, 50KHz BIA for getting BIA/Respiration, and 10~50Hz GSR for measuring electrical characteristics of skin. To this end, BIA signal is separated by line filter and high impedance element and the interference between signals could be minimized by switching in time domain to separate ECG and GSR signals having the similar frequency range. ECG, heart rate and respiration are measured by the simulator based on the implemented circuit and BIA and GSR impedance are verified using standard resistance. Also, we made an experiment this method to human body and found the possibility of detecting bio-signals. PMID- 17282673 TI - Enabling Distributed Addition of Secure Access to Patient's Records in A Tele Referring Group. AB - Protecting the privacy of patients' Electronic Health Records (EHR) while providing timely health care is an important issue in e-medicine. In this paper, we introduce an emerging problem of secure access to EHR added by the patient directly or by a physician who is not primary. We identify the design requirements, propose our solutions, and demonstrate that our solutions satisfy the design requirements. PMID- 17282674 TI - A low distorsion and reversible watermark: application to angiographic images of the retina. AB - Medical image security can be enhanced using watermarking, which allows embedding the protection information as a digital signature, by modifying the pixel gray levels of the image. In this paper we propose a reversible watermarking scheme which guarantees that once the embedded message is read, alterations introduced during the insertion process can be removed from the image. Thereafter, original pixel gray levels of the image are restored. The proposed approach relies on estimation of image signal that is invariant to the insertion process, and permits to introduce a very slight watermark within the image. In fact, the insertion process adds or subtracts at least one gray level to the pixels of the original image. Depending on the image to be watermarked, in our case angiographic images of the retina, it is expected that such image alteration will not have any impact on the diagnosis quality, and consequently that the watermark can be kept within the image while this one is interpreted. PMID- 17282675 TI - A secure distribution method for digitized image scan using a two-step wavelet based technique: A Telemedicine Case. AB - The objective of this paper is to present a secure distribution method to distribute healthcare records (e.g. video streams and digitized image scans). The availability of prompt and expert medical care can meaningfully improve health care services in understaffed rural and remote areas, sharing of available facilities, and medical records referral. Here, a secure method is developed for distributing healthcare records, using a two-step wavelet based technique; first, a 2-level db8 wavelets transform for textual elimination, and later a 4-level db8 wavelets transform for digital watermarking. The first db8 wavelets are used to detect and eliminate textual information found on images for protecting data privacy and confidentiality. The second db8 wavelets are to secure and impose imperceptible marks to identify the owner; track authorized users, or detects malicious tampering of documents. Experiments were performed on different digitized image scans. The experimental results have illustrated that both wavelet-based methods are conceptually simple and able to effectively detect textual information while our watermark technique is robust to noise and compression. PMID- 17282676 TI - Integrating legacy medical data sensors in a wireless network infrastucture. AB - In the process of developing a wireless networking solution to provide effective field-deployable communications and telemetry support for rescuers during major natural disasters, we are faced with the task of interfacing the multitude of medical and other legacy data collection sensors to the network grid. In this paper, we detail a number of solutions, with particular attention given to the issue of data security. The chosen implementation allows for sensor control and management from remote network locations, while the sensors can wirelessly transmit their data to nearby network nodes securely, utilizing the latest commercially available cryptography solutions. Initial testing validates the design choices, while the network-enabled sensors are being integrated in the overall wireless network security framework. PMID- 17282677 TI - Atheroma: is Calcium Important or Not? A Modelling Study of Stress Within the Atheromatous Fibrous Cap in Relation to Position and Size of Calcium Deposits. AB - Atheromatous plaque rupture is the cause of the majority of strokes and heart attacks in the developed world. The role of calcium deposits and their contribution to plaque vulnerability are controversial. Some studies have suggested that calcified plaque tends to be more stable whereas others have suggested the opposite. This study uses a finite element model to evaluate the effect of calcium deposits on the stress within the fibrous cap by varying their location and size. Plaque fibrous cap, lipid pool and calcification were modeled as hyperelastic, isotropic, (nearly) incompressible materials with different properties for large deformation analysis by assigning time-dependent pressure loading on the lumen wall. The stress and strain contours were illustrated for each condition for comparison. Von Mises stress only increases up to 1.5% when varying the location of calcification in the lipid pool distant to the fibrous cap. Calcification in the fibrous cap leads to a 43% increase of Von Mises stress when compared with that in the lipid pool. An increase of 100% of calcification area leads to a 15% stress increase in the fibrous cap. Calcification in the lipid pool does not increase fibrous cap stress when it is distant to the fibrous cap, whilst large areas of calcification close to or in the fibrous cap may lead to a high stress concentration within the fibrous cap, which may cause plaque rupture. PMID- 17282678 TI - A crevice bubble growth model for the analysis of decompression sickness. AB - Decompression sickness is a series of symptoms associated with the formation of bubbles in the body during decompression. Bubbles have been observed both stationary in the tissues and moving with the blood. It has been proposed that the bubbles observed in the blood grow directly on the vessel walls. A possible mechanism for this is the growth of bubbles in sites resembling crevices in the endothelium. A crevice bubble growth model is derived based on existing tissue bubble models and tested with physiologically realistic parameters. PMID- 17282679 TI - Endothelium-independent Vasorelaxant Effect of the Phyto-oestrogen Biochanin A on Rat Thoracic Aorta. AB - Epidemiological data suggest that the incidence of cardiovascular disease is reduced in people who have a high intake of phytoestrogens. The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanisms of action remain unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on rat thoracic aorta. Isolated aortic rings were suspended in individual organ baths and isometric tension was measured. Biochanin A induced significant relaxation in rings with or without endothelium. Contractile responses induced by phenylephrine (PE), KCl and CaCl2were antagonized by 10-7~10-4mol/L biochanin A. The transient contraction elicited by PE was significantly attenuated by 10-5mol/L biochanin A in Ca2+-free medium. The relaxant effect of biochanin A was significantly inhibited by pretreatment with the K+channel antagonists tetraethylammonium and glibenclamide in endothelium-denuded aorta. We conclude that biochanin A induces an endothelium-independent relaxation in rat aortic rings. The underlying mechanism may involve the blockage of Ca2+entry through both voltage-dependent and receptor-operated Ca2+channels, the inhibition of intracellular Ca2+release, and the activation of large-conductance Ca2+-activated K+channels and ATP-sensitive K+channels. PMID- 17282680 TI - A non-invasive system for assessment of aortic stiffness in clinical practice. AB - Previously aortic stiffness is frequently assessed through pulse pressure and pulse wave velocity (PWV) measurements. However, these methods need aortic pressure obtained by catheterization. A new model has been developed to rapidly determine the aortic pressure profile and simultaneously calculate aortic stiffness. Comparison between the aortic pressure result obtained from this and catheterization data demonstrates good agreement, while this method is non invasive. This totally non-invasive method should be useful in assessing arteriosclerotic disease in clinical setting. PMID- 17282681 TI - Investigation of Arterial Waves using Phase Averaging. AB - In this paper the development of objective criteria for data reduction, parameter estimations and phenomenological description of arterial pressure pulses are presented. The additional challenge of distinguishing between the cyclical and incoherent contributions to the wave form is also considered. By applying the technique of phase averaging to a series of heart beats, a characteristic pulse was determined. It was shown that the beats from a paced heart are very similar and while beats from an unpaced heart will vary significantly in time and amplitude. The appropriate choice of a reference point is critical in generating phase averages that embody the characteristic behaviour. PMID- 17282682 TI - Multipurpose piezoelectrical ceramic materials and high performance transducers are used for the ultrasonic medicine. AB - This paper briefly reports on preparations and applications of two kind multipurpose medical piezoelectrical ultrasonic transducer materials, high performance medical ultrasonic diagnosis transducers and medical ultrasonic therapy transducers in present work, then, some problems of the piezoelectric materials and devices used for the ultrasonic medicine which need further researches are pointed out. PMID- 17282683 TI - A new approach to investigate wave dissipation in viscoelastic tubes: application of Wave Intensity Analysis. AB - Wave dissipation in elastic and viscoelastic medium has been investigated extensively in the frequency domain. The aim of this study is to examine the pattern of wave dissipation in the time-domain using Wave Intensity Analysis. A single semi-sinusoidal pulse was generated in 8mm and 16mm diameter tubes; each is of 200cm in length. Pressure and flow measurements were taken at intervals of 5 cm along the tube. In order to examine the effect of the wall mechanical properties on wave dissipation, we also modified the wall of the 16mm tube; a thread of strong cotton was wound with a pitch of approximately 30° around the circumference of the tube in the longitudinal direction. The separated forward pressure, wave intensity and wave energy were calculated using Wave Intensity Analysis. The amplitudes of the forward pressure wave, wave intensity and wave energy dissipated exponentially with distance. In the 8mm diameter tube, the dissipation of forward pressure, wave intensity and wave energy were greater than those in 16mm tube. For the same sized of tube, there was no significant difference in the dissipation of forward pressure, wave intensity and wave energy between the modified and normal wall tubes. It is concluded that the size of tube has a significant effect on the wave dissipation but the mechanical properties of the wall do not have a discernable effect on wave dissipation. PMID- 17282684 TI - Lipoprotein transport in the blood stream to the arterial wall in a carotid artery bifurcation. AB - The carotid arteries are a common site of atherosclerotic plaque formation, which has been linked to the blood flow patterns and the mass transport phenomenon. The purpose of this research was to study the lipid transport in a human carotid artery model, focusing on the effects of local geometric and hemodynamic factors on mass transfer from blood flow to vessel wall and its concentration at the luminal surface of the artery. The Reynolds number, 250, and the Schmidt number, 6.66x105, were selected to model the mass transfer of LDL macro molecules, and in order to see the effect of Reynolds and Schmidt numbers to mass transport, the model was analyzed with different conditions. The steady state flow was used for two dimensional carotid geometry. At the inlet, the blood flow was assumed a steady fully developed laminar velocity profile with a uniform LDL concentration. The vessel wall was assumed permeable to water and semi-permeable to LDL macro molecules. The problem was analyzed with the finite element method. The results show 26% increase of LDL concentration from inlet value at the luminal surface of the artery located in the separated flow region. The maximum value of LDL concentration occurred at the separation point. PMID- 17282685 TI - Analysis of the simulative experimental data related to the effect of the myocardial bridge on the blood flow of the coronary artery. AB - The compression of the mural coronary artery also exists in the diastole. We make a myocardial bridging simulator and build an experimental model to study the status of the compression. Through the simulative experiment, we make a numerical value simulation which depicts the effect of the myocardial bridge on the blood flow of the coronary artery during systole and diastole. With the help of the CFO, we make an analysis of the experimental data. Data and discussions are given as references for relevant researchers. PMID- 17282686 TI - Experimental Research on Balloon-expandable Endovascular Stent Expansion. AB - The application background and experimental research overview of medical endovascular stent are presented. Based on the analytical comparison of the current research achievements, the life cycle of medical vascular stent, which is composed of three phases of mounting, deployment and long-term in vivo service, is pointed out and the characteristics of stent expansion process in the life cycle are emphasized on. The experimental scheme of in vitro stent expansion based on the machine vision technology in LabVIEW is presented. The selected component devices and measurement program for experiment are expatiated. A special drug-loading stent was expanded on the assembled platform of selected equipments and experimental results are analyzed. The experimental scheme presented in the paper provides powerful experimental support for the computer simulation of stent expansion process by the finite element analysis. PMID- 17282687 TI - Inhibition of Mitochondrial Permeability Transition Pore: A Possible Mechanism for Cardioprotection Conferred by Pretreatment with Tanshinone IIA. AB - The objective of this study was to determine whether the mitochondrial permeability transition pore plays a role in cardioprotection induced by tanshinone IIA. Isolated rat hearts were subjected to 30 min regional ischemia by ligation of the left anterior descending artery followed by 120 min reperfusion. Ischemic preconditioning (IPC) was achieved by two 5-min periods of global ischemia separated by 5 min of reperfusion. Pretreatment with tanshinone reduced the infarct size which was associated with improved recovery of left ventricular contractility as with IPC. Perfusion with 100 muM 5-hydroxydecanoate (5-HD) attenuated the cardioprotection induced by tanshinone. In mitochondria isolated from untreated hearts, tanshinone inhibited pore opening dose-dependently, and this effect was abolished by blocking the mitochondrial ATP sensitive potassium channel with 5-HD. We conclude that pretreatment with tanshinone IIA provides similar cardioprotection to IPC, this effect may be via inhibiting the pore opening during reperfusion, and the mitochondrial ATP sensitive potassium channel may play a role in mediating the pore inhibition induced by tanshinone IIA. PMID- 17282688 TI - The relationship of ventricular dynamics and mitochondrial nitric oxide synthase activity in septic shock models. AB - The aim of the present study was to investigate the role of mitochondrial nitric oxide synthase (mtNOS) in the septic shock and analyze its relationship to ventricular contractility. Two models of septic shock [lipopolysaccharide (LPS) induced and cecal ligation and puncture (CLP)-induced] were used. There was a significant depression of ventricular contractile parameters recorded in the late stage of the septic shock. After measurement of ventricular-dynamic parameters, mitochondrial and cytoplasmic fractions were isolated and their nitric oxide synthase (NOS) activity was assessed using a NOS activity assay kit. Both models showed a larger increase in mitochondrial NOS activity than that in cytosol. However, the increase in mtNOS activity in the LPS-induced shock model was less pronounced than in the CLP-induced model. Regression analysis shows that mitochondrial nitric oxide synthase (mtNOS) activity is negatively correlative to the left ventricular developed pressure in CLP model. The results suggest that mitochondrial NOS may mainly contribute to the ventricular depression in the septic shock. PMID- 17282689 TI - Interleukin-2 Improves Vascular Functions in Streptozotocin-induced Diabetic Rats. AB - To investigate changes in vascular functions in streptozotocin (STZ)-induced diabetic rats and the effect of interleukin-2 (IL-2), male Sprague-Dawley rats were randomly divided into a normal group, a diabetic control group, and diabetic groups treated with a low dose (5000 U/kg/d) or a high dose of IL-2 (50000 U/kg/d) for five weeks. Rats were injected with STZ (60 mg/kg, i.p.) to induce diabetes. The contractions in response to KCl, phenylephrine (PE), and CaCl2, and the vasorelaxant effect of acetylcholine (ACh) on rings from thoracic aortae preconstricted with PE were determined using organ bath technique. In the diabetic group, the contractile responses to PE were significantly impaired. Treatment with IL-2 improved this response, but the high dose was less effective. However, IL-2 attenuated the contractile response to KCl in the diabetic groups in a dose-dependent manner. The high concentration of IL-2 decreased the contractile response to CaCl2. ACh caused a dose dependent relaxation of aortic rings that was impaired in the diabetic group. The vascular responses in IL-2 treated groups were preserved. The results indicate that IL-2 can improve vascular function in diabetic rat. PMID- 17282690 TI - Computational study of stented aortic arch aneurysms. AB - This computational study is motivated by the fact that there is still incomplete knowledge to date about hemodynamics of stented aortic arch aneurysms harboring a bleb. The hemodynamics in the stented and nonstented models of aortic aneurysms were analyzed and compared using the method of computational fluid dynamics. Flow activities inside the stented aneurysm model were significantly diminished, specifically the pressure and wall shear stress in the bleb were decreased, thus promoting intra-aneurysmal thrombus development and attenuating aneurysm rupture risk. The present study indicated that it is effective to treat aortic arch aneurysms with endovascular stents. PMID- 17282691 TI - Analytical and Numerical Studies of Volume Measurement using Conductance Catheter Techniques. AB - Calculation of intra-ventricular blood volume using the impedance electrode technique suffers from inaccuracy arising from irregularity in ventricular geometry and non-uniformity in imposed electric fields. This is particularly evident in the right ventricle. To investigate this problem, we present analytical and numerical solutions for the electric field in a conductor with asymmetrical source electrodes. The results show the effects of field non uniformity, and a potential improvement in using dual-excitation electrodes. We plan to extend these techniques to develop improved electrode configurations for use in blood volume measurements in the right ventricle. PMID- 17282692 TI - A combined haemodynamic and biochemical model of cerebral autoregulation. AB - The feedback processes that control the blood supply to the brain, collectively termed cerebral autoregulation, are many and complex. Failure of this mechanism is implicated in a number of conditions. However, in a clinical setting the number of variables that can be measured non-invasively is extremely limited. In addition, current models are either too crude, and not physiologically meaningful, or so complex that analysis is difficult. In this paper a new compact, but physiologically meaningful, model is presented, based on smooth muscle cells within a vessel model, integrated within a full haemodynamic model. Preliminary results show realistic behaviour. PMID- 17282693 TI - Vessel wall temperature estimation for novel short term thermal balloon angioplasty: study of thermal environment. AB - We have been proposing novel thermal balloon angioplasty, photo-thermo dynamic balloon angioplasty (PT-DBA). PTDBA realized <10s short term heating that can prevent surrounding tissue thermal injury and low pressure dilatation that can prevent restenosis in chronic phase. We aim to determine the most efficient heating condition suit to individual symptom with pre-operation thermal simulation. We analyzed the flow dynamics and heat convection inside the balloon, and investigated heat conduction of balloon film to establish the temperature estimation method among vessel wall. Compared with ex vivo temperature measurement experiment, we concluded that the factors need to be considered for the establishment would be the heat conduction of the flow inside PTDB, heat conduction at the balloon film, and contact thermal resistance between the balloon film and vessel wall. PMID- 17282694 TI - Experimental study of a complete anastomosis model for the coronary artery bypass. AB - Local hemodynamics of complete bypass model under steady flow condition was investigated using the instantaneous velocity fields acquired by Particle Image Velocimetry (PIV). At proximal anastomosis a low velocity region was found near the heel along the graft inner wall and a stagnation point was found near the toe. The velocity profile was relatively smooth except slightly skew toward the graft outer wall. Near the occluded end of the distal anastomosis, the fluid was found almost stationary although a weak recirculation occurred. Higher wall shear stress was found to be located at the toe and the artery bed near the toe of the distal anastomosis. PMID- 17282695 TI - In vivo evaluation of oxygen consumption by arteriolar walls in skeletal muscle. AB - To estimate the oxygen consumption rate of arteriolar walls we measured the intra and perivascular partial oxygen tension (PO2) of arterioles in rat cremaster muscle, both at resting and vasodilating states by phosphorescence quenching technique. Using measured intra- and perivascular PO2values, oxygen consumption rates were determined based on Krogh-Erlang analysis. We found a significant drop in PO2in the arterioles after branching. We found that the vascular oxygen consumption rates of functional arterioles were 100-1000 times greater than those seen in in vitro experiments. These results strongly support the hypothesis that arteriolar walls consume a significant amount of oxygen as compared with the surrounding tissue. Furthermore, the reduction of vascular tone of arteriolar walls may facilitate an efficient supply of oxygen to the surrounding tissue. PMID- 17282696 TI - Conceptual modeling of cardiovascular sounds. AB - In this paper, it is shown that the main source of mechanical energy of cardiovascular (CV) system i.e., rhythmic heart contraction is transformed to the oscillations of the CV walls and blood flow, and finally CV acoustical waves. These waves propagate through both blood flow (hemodynamical pathways) and tissues (viscoelastical pathways) toward the skin. Nonetheless, the CV walls could be assumed as the source of acoustical waves, since they act as the interface between blood flows and other tissues including skin. After obtaining the approximate accelerations of CV walls from pressure-flow (PF) models, we also needed to model the viscoelastical pathways until the skin. Some improvements on PF models were fulfilled to present small variations of blood pressure such as dicrotic notch. The turbulence occurrence was also noticed to and conceptually modeled. The total homomorphic model could conceptually show the relations of CV sounds with CV characterizations and tissue specifications. Thus, it could be helpful to assess CV system in order to diagnose CV diseases via CV sounds. The CV sounds recorded from the skin of any place (e.g., chest or arm) could be simulated via this model, if the hemodynamical and viscoelastical parameters especially for the region under that place are obtained. PMID- 17282697 TI - A computer simulation of blood flow in arterial networks, including blood non newtonian models and arterial stenosis. AB - The goals of this research are: 1. To construct a software that can determine pressure and flow at different points of an arbitrary arterial network; 2. To investigate the effect of non-Newtonian model on pressure and flow waves in comparison with Newtonian model. The main assumptions in our physical model are: 1- Blood flow is one dimensional and in axial direction; 2- Arteries are elastic cylindrical tubes; 3-Blood flow is laminar. The method of analysis is finite element technique. Three element types have been used: 1- Artery element for an unobstructed healthy artery, 2- Branch element for three or more artery element connections and 3- Stenosis element for an artery stenosis. Arterioles and capillary beds at the ends of arteries have been electrically modeled as a "developed Windkessel model" that includes a capacitance and a resistance in series and a resistance parallel with them. The numerical solvers were written in C++ computer language. PMID- 17282698 TI - A study of intravascular brachytherapy treatment planning in peripheral arteries. AB - A two-step method to determine the seed parameters for the planning of peripheral intravascular brachytherapy, which took the actual vessel geometry into consideration, was developed. Firstly, the characteristics of the vessel geometry was obtained by using active navigation; Then a method combined genetic algorithm with BFGS algorithm was applied to optimize the number of seeds, and the parameters associated with each seed such as the position, and the dwell time. Application of the method to a phantom model and three animal models of stenosis shows that promising result could be obtained, and the planning of peripheral intravascular brachytherapy should take actual vessel geometry into consideration. PMID- 17282699 TI - A Bond Graph Approach to the Modeling of Fluid-Solid Interaction in Cardiovascuular System's Pulsatile Flow. AB - A bond graph model of entire cardiovascular system is developed in this paper. Although relying on the concepts of previously developed lumped-parameter models, this new model benefits from some advantages of general system theory which allows the modeler to include as many details as necessary. Specifically, inclusion of pace making mechanism has become much easier. The pace making mechanism is not, however, included in this stage of model development. Modular sources of effor are, instead, predicted in the model to genrate synthetic signals close to what occurs in reality. The model is simulated and results of simulation are compared with widely available data of normal cardiovascular system's pressure-flow performance. It has been shown that they are of a good agreement and the model could successfully simuulate performance of the human cardiovascular system. PMID- 17282700 TI - Force enhancement and mechanisms of contraction in skeletal muscle. PMID- 17282701 TI - Flexure-based Manipulator for Active Handheld Microsurgical Instrument. AB - This paper presents the design and initial experimental results of a flexure based parallel manipulator that is actuated by three piezoelectric stacks. The manipulator is for an active handheld tremor canceling device for microsurgery. By using flexures to approximate pin and ball joints, errors due to friction, backlash, and imperfect assemblies have been eliminated. The results show that the manipulator is capable of tracking motions similar to physiological tremor in amplitude and frequency. The workspace of the manipulator is more than 7 times larger than the tremor space in the x and y axes, and about 1.5 times larger in the z axis. One dimensional and three dimensional tracking tests had rms errors of 6.5 μm and 12.1 μm respectively. PMID- 17282702 TI - Non-invasive Fiber Tracking on Diffusion Tensor MRI Using High-Temperature Superconducting Tape RF coil. AB - High-temperature superconducting (HTS) coil is one of the best ways to increase the signal-to-noise ratio (SNR). Bi2Sr2Ca2Cu3Ox (Bi-2223) tapes were suitable to use because of the easier fabrications and lower cost. In this study, we built HTS Bi-2223 tape coils and demonstrated that the SNR of using the HTS tape coil was 3 or 4 folds higher than that of the traditional copper coil for a rat brain MR study. Acquisition time of MR diffusion tensor imaging (DTI) can be reduced by factor of 9 for the same signal-to-noise. Accuracy of fiber tracking using DTI is also significantly improved by a factor of 2.5 or so using HTS coil. In summary, with this HTSC system, a 3T MR system could reach the high signal-to-noise of 12 T MR system with the advantage of less T2 shortening effects at high field. Currents researches are focused on brain connectivity and fMRI studies. PMID- 17282703 TI - Design, construction and evaluation of an electromechanical stance-control knee ankle-foot orthosis. AB - A new electromechanical Stance-Control Knee-Ankle-Foot Orthosis (SCKAFO) was designed to provide improved gait for people with knee-extensor weakness. This SCKAFO inhibits knee flexion at any knee angle while allowing knee extension during weight bearing. During swing or other non-weight bearing activities, the SCKAFO allows free knee motion. A prototype joint was mechanically tested to determine the moment at failure, loading behaviour, and device safety. Quantitative kinematic gait analysis of three able-bodied subjects and three knee ankle-foot-orthosis (KAFO) users showed that the new SCKAFO had a desired minimal effect on able-bodied walking gait. The SCKAFO permitted a mean increase in sagittal knee motion (488%) during swing for the three KAFO users and a reduction in pelvic obliquity and hip abduction angle abnormalities during terminal stance and swing for two KAFO users. PMID- 17282704 TI - Development of an interactive motivating tool for rehabilitation movements. AB - In this paper, an interactive tool, including three computer games controlled via the center of foot pressure (COP) trajectory biofeedback, was designed to aid in pressure balance for rehabilitating persons with balance disorders. The games interact in real-time with the Vista Medical Force Sensitive Applications software and pressure mat. The main goal of this research was to employ attractive and motivational learning techniques, using equipment that is available to a large population, to increase volume of exercise practice and to retain the patient's attention. Questionnaires regarding the motivational aspects of the games were administered to 15 subjects (7 patients). The results indicate that the tools were indeed attractive, motivational and an improvement to conventional exercise regimes. PMID- 17282705 TI - Comparison of Parameter Estimations Using Dual-Input and Arterial-Input in Liver Kinetic Studies of FDG Metabolism. AB - Liver kinetic study of [18F]2-fluoro-2-deoxy-D-glucose (FDG) metabolism in human body is an important tool for functional modeling and glucose metabolic rate estimation. In general, the arterial blood time-activity curve (TAC) and the tissue TAC are required as the input and output functions for the kinetic model. For liver study, however, the arterial-input may be not consistent with the actual model input because the liver has a dual blood supply from the hepatic artery (HA) and the portal vein (PV) to the liver. In this study, the result of model parameter estimation using dual-input function is compared with that using arterial-input function. First, a dynamic positron emission tomography (PET) experiment is performed after injection of FDG into the human body. The TACs of aortic blood, PV blood, and five regions of interest (ROIs) in liver are obtained from the PET image. Then, the dual-input curve is generated by calculating weighted sum of both the arterial and PV input curves. Finally, the five liver ROIs' kinetic parameters are estimated with arterial-input and dual input functions respectively. The results indicate that the two methods provide different parameter estimations and the dual-input function may lead to more accurate parameter estimation. PMID- 17282706 TI - Quantitation of renal function based on two-compartmental modeling of renal pelvis. AB - The primary functions of the kidney are: (i) to get rid of the body waste materials that are either ingested or produced by metabolism, and (ii) to control the volume and composition of the body fluids. Herein, we provide a noninvasive methodology to assess physiological function of the kidneys. For this purpose, we analyze the renograms with 2-compartmental modelling of the kidney-renal outflow system, and therefrom compute the amount of flow of renal radionuclide into and out of the renal pelvis compartment. The derived information of uptake (k/A) and washout (e(beta/2V2)t sinhAt) rates can be of considerable use. The paper provides a number of case studies for the verification of the derived system governing equations against clinical renograms. PMID- 17282707 TI - A new model for drug interactions and optimal drug dosing. AB - Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account. We propose a new method to study drug interactions considering also their side effects and to identify optimal drug dosing. The model is consistent with clinical knowledge and can explain previously published experimental results, improving our understanding of the characteristics of drug combinations used in clinical practice. PMID- 17282709 TI - Distributed model of human glucose metabolism and computer simulation study. AB - Metabolism is the basic character of living activity. Through the research on the physiological process of carbohydrate metabolism, we have established the compartment model of organ glucose metabolism, which is incorporated into our multi-element non-linear cardiovascular model. The simulation of the incorporated model can reflect the status of carbohydrate metabolism under different situations. This will help to understand the mechanism of metabolism procedure and give advices on curing metabolism diseases. PMID- 17282708 TI - Modeling the influence of the pulmonary pressure-volume curve on gas exchange. AB - Current models of lung mechanics and gas exchange act independently to simulate variations in pressure-volume (PV) and ventilation-perfusion (V/Q) properties in the lungs respectively. However, changes in ventilator pressures can cause alveoli recruitment, collapse or over-distension causing V/Q changes in the lungs that are unaccounted for in these models. A compartmental model of the lungs is presented that is based on a physiological interpretation of lung function and simulates each alveolus individually. By combining this model with currently available lung mechanics and gas exchange models, the effect of changing ventilator settings on gas exchange could be simulated. The model is shown to simulate experimentally measured static PV data from an ARDS patient with an accuracy equivalent to that achieved by the sigmoid function. It could enable quantification of variations in V/Q in the lungs and also gives estimates of other physiological lung properties such as lung density and alveoli compliance. The alveoli model offers a physiologically relevant method of simulating the PV relationship in the lungs and its influence of gas exchange. PMID- 17282710 TI - Optimal infusion policy of intravenous morphine and ketamine - A Mixed-Integer Linear Programming application. AB - Recently, a model for drug interactions considering also side effects has been proposed. According to this model, the effect compartment concentration range maximizing the global well-being of the patient can be identified. This optimal range represents the set which should be targeted by drug infusion. In this work, we apply this novel model to the clinically relevant combination of intravenous morphine and ketamine. The optimal range is identified and its center used as the reference value for controller design. The control problem can be formulated as consisting of mixed continuous and discrete parts. By solving the optimal control problem, the optimal infusion policy is identified minimizing the drug consumption. PMID- 17282711 TI - Exact Linearisation and Control of a HIV-1 Predator-Prey Model. AB - The aim of this work was to develop a HIV-1 control strategy based on the nonlinear geometric control theory. Such a strategy was applied on a three variables deterministic model that describes the characteristic stages of the HIV 1 infection. The control design developed in this work allows the exact linearisation of the model. The results show that the nonlinear control developed is effective to minimize the viral load in the initial stage and the asymptomatic period of the infection. The main characteristic of this type of pharmacological control is the antiretroviral drug dosage in a proportional way to the viral population. PMID- 17282712 TI - Frequency-selective analysis of multichannel magnetic resonance spectroscopy data. AB - In several practical magnetic resonance spectroscopy (MRS) applications the user is interested only in the spectral content of a specific frequency band of the spectrum. A frequency-selective (or sub-band) method estimates only the parameters of those spectroscopic components that lie in a pre-selected frequency band of the spectrum in a computationally efficient manner. Multichannel MRS is a technique that employs phased-array receive coils to increase the signal-to-noise ratio (SNR) in the spectra by combining several simultaneous measurements of the magnetic resonance (MR) relaxation of an excited sample. In this paper we suggest a frequency-selective multichannel parameter estimation approach that combines the appealing features (high speed and improved SNR) of the two techniques above. The presented method shows parameter estimation accuracies comparable to those of existing fullband multichannel techniques in the high SNR case, but at a considerably lower computational complexity, and significantly better parameter estimation accuracies in low SNR scenarios. PMID- 17282713 TI - A classification method of hand movements using multi channel electrode. AB - In this study, we describe the classification method of hand movements using 96 channels matrix-type(16times6) of multi channel surface electrode. Today, there are many systems that use the EMG as a control signal. As for those ordinary systems, it has some problem like most of them require the definition of measuring position. We design the new system with multi channel electrode to solve some of those conventional problems. Our system that has 96 channels electrode does not need to select a particular electrode position. Only attaching this electrode, we can obtain correct EMG and this way means providing with a simple and easy way. The purpose of this study is development of the EMG pattern recognition method using multi channel electrode. From measured 96 channels EMG data, we chose one line (16channels) of this electrode with the smallest noise. The EMG signal is recognized by canonical discriminant analysis. In order to recognize the EMG signal, the first three eigenvectors are chosen to form a discriminant space. And Euclidean distance is applied to classify the EMG. From the experiment in this method, we can discriminate 12 movements of the hand including four finger movements. And the recognition rate that can be done in real-time was measured at 80 percent on the average. PMID- 17282714 TI - Rank Based Selection of Electrode Positions for a Multi-Lead ECG Electrode Array. AB - Methods for noninvasive imaging of electrical function of the heart seem to become a clinical standard procedure the next years. Thus, the overall procedure has to meet clinical requirements as easy and fast application. In this study we propose a new electrode array meeting clinical requirements such as easy to apply and compatibility with routine leads. Within body surface regions of high sensitivity, identified in a prior, information content based study, the number of required electrodes was optimized using effort-gain plots. These plots were generated by applying a so called type one detector criterion. The optimal array was selected from a set of 12 electrode arrays. Each of them consists of two L shaped regular spaced parts. The optimal array was found by comparing several layouts and electrode densities to the electrode array we use for clinical studies. It consists of 125 electrodes with a regular spacing between 2cm and 3cm. PMID- 17282715 TI - Adaptive left ventricular ejection time estimation using multiple peripheral pressure waveforms. AB - An adaptive approach is proposed for the problem of left ventricular ejection time (LVET) estimation using peripheral pressure waveform signals. The proposed algorithm, which makes use of 2 peripheral pressure measurements, makes it possible to adaptively estimate the LVET in response to different cardiovascular physiologic states. The algorithm builds on features obtained from global and branch-specific characterization of the cardiovascular circulation as well as waveform features to dramatically improve the accuracy of LVET estimation. The performance of the proposed approach is evaluated with respect to its heart-rate based conventional counterpart, which shows approximately 40% improvement of estimation accuracy in terms of R2values □ from 0.6655 for the conventional waveform-based approach to 0.9222 for the proposed approach. PMID- 17282716 TI - One-Versus-the-Rest(OVR) Algorithm: An Extension of Common Spatial Patterns(CSP) Algorithm to Multi-class Case. AB - Extraction of relevant features that capture the invariant characteristics specific to each brain state is very important in order to implement a suitable Brain-Computer Interface (BCI) system. This paper presents an algorithm called One-Versus-the-Rest (OVR), which is an extension of a well-known method called Common Spatial Patterns (CSP) to multi-class case, to extract signal components specific to one condition from electroencephalography (EEG) dataa sets of multiple conditions. The alagorithm was previously mentioned in [7], yet without an elaborate description. In this paper, detailed mathematicaal derivation of the algorithm is given, followed by a computer simulation. The computer simulation suggests that the algorithm is capable of reconstructing the actual specific part of each condition with high quality, even when the data are contaminated with considerable noise. We also hint future possible applications of the algorithm in the context of BCI at the end of the paper. PMID- 17282717 TI - Evaluation of health care related web resources based on web citation analysis and other quality criteria. AB - Automatic system for ranking of educational health care related web resources based on quality criteria was developed. Automatic retrieval of new web resources from well-known directories followed by their automatic evaluation is a keystone of the system. The system provides this information: a) location of the resource and its author, b) number of back links to the resource, c) checks presence of electronic labels of quality. Currently the system encompasses more than 500 links to educational web resources divided into 47 medical specialities. The resources in all categories are ranked according to their link popularity, the electronic labels of quality are presented. History of link popularity is recorded and might be displayed at every resource. There are 2 language editions. The system operates automatically, the editors check and correct the retrieved values. The described system adds to webcite indexing criteria for objective evaluation of quality of webpages. It is useful for the selection of optimum education resources in health care. PMID- 17282718 TI - Manufacturing Student Leaders and Cultivating Six Ingredients for Success of an EMBS Student Organization. AB - We present in this paper seven individual qualities of student leadership and emphasize six ingredients for successfully maintaining EMBS student clubs and chapters. Particularly, we provide a comprehensive view on segmented functions of an EMBS student organization, and discuss in detail the executive operations such as strategy management, program management with minimum-cost scheduling, recruitment and member development, seeking opportunities and supports from internal and external collaborations, building up information platform for communicating and construct institutional rules for indemnification of a health development. Our insights could help generate a general framework for sustainable development of an EMBS student organization. PMID- 17282719 TI - A biomedical engineering career in the government. AB - Dr. Demir will give an overview of biomedical engineering (BME) career opportunities in industry, academia and government; and she will provide comparisons. She will also present her career journey in industry, academia and government. She will focus on the skills and knowledge needed for a BME career in government. She will present the employment growth for BME. PMID- 17282721 TI - The challenges of biomedical engineering education in latin america. AB - The broad scope of Biomedical Engineering requires careful planning when designing educational programs of the discipline, which must prepare students for a successful professional performance in a constantly changing field. Throughout the world, BME education must adapt to the dynamic concept of the profession and its scope. In this paper we present the issues that should be addressed for the successful preparation of future BM engineers in Latin America. PMID- 17282720 TI - Society: the catalyst of health informatics. AB - The rapid progress in health informatics is motivating technical innovations globally in many fields like diagnostics, radiological information systems etc. In the middle of all these galloping advances, the need for integration of associated technologies is significant. In addition, fully concerted functioning of the associated healthcare professionals, with attention to certain sections of society deserves a special emphasis. This paper highlights the allied groups of people; key interaction challenges and suggests the cadence through which the fruits of their efforts directly reach the ordinary citizen. PMID- 17282722 TI - Strategic alliance as a competitive tactics for biological-pharmacy industry. AB - Biological-pharmacy industry refers to biotechnology companies and pharmacy makers. Because of the uncertainty and time-lag in the field of biological pharmacy, the former is confronted with lacking of capital and the later is faced with improving technique-innovation and product-exploitation. This paper analyzes basic operation principle of strategic alliance, and related strategies are also put forward for biological-pharmacy enterprise to carry out. PMID- 17282723 TI - A fuzzy cognitive map hierarchical model for differential diagnosis of dysarthrias and apraxia of speech. AB - This paper presents a novel soft computing system for differential diagnosis of the dysarthrias and apraxia of speech based on well accepted dysarthrias' classification system used by speech and language pathologists. The dysarthrias and apraxia are complex disorders of speech because they represent a variety of neurological disturbances that can potentially affect every component of speech production. Since an accurate diagnosis is a very challenging task for the clinician, the under development system based on hierarchical Fuzzy Cognitive Maps (FCMs) will be used as a "second opinion" or training system. The hierarchical FCM differential diagnosis system is capable of differentiating between the six types of dysarthria as well as apraxia. The system was tested using published case studies and real patients and examples are presented here. PMID- 17282724 TI - Research on Medical Diagnosis Decision Support System for Acid-base Disturbance Based on Support Vector Machine. AB - Support Vector Machine (SVM) is a new learning technique based on Statistical Learning Theory (SLT). In this paper, a Medical Diagnosis Decision System (MDDSS) based on SVM has been established to intellectively diagnose 4 types of acid-base disturbance. SVM was originally developed for two-class classification. It is extended to solve multi-class classification problem named hierarchical SVM with clustering algorithm based on stepwise decomposition. Compared with other classical classification techniques, SVM not only has more solid theoretical foundation, it also has greater generalization ability as our experiment demonstrates. Thus, SVM exhibits its great potential in MDDSS. PMID- 17282725 TI - A comparison of multi-layer neural network and logistic regression in hereditary non-polyposis colorectal cancer risk assessment. AB - Hereditary non-polyposis colorectal cancer (HN-PCC) is one of the most common autosomal dominant diseases in developed countries. Here, we report on a system to identify the risk of a family having HNPCC based on its history. This is important since population-wide genetic screening for HNPCC is not currently considered feasible due to its complexity and expense. If the risk of a family having HNPCC can be identified/asessed, then only the high risk fraction of the population would undergo intensive screening. Here, we have developed a Multi Layer Feed-Forward Neural Network to classify families into high-, intermediate- and low-risk categories and compared the result with the benchmark logistic regression model. PMID- 17282726 TI - Fuzzy Classifier based on Muscle Fatigue Parameters. AB - This paper presents the development of a decision aid tool based on a fuzzy classifier. The goal was to obtain a system that could support a physician who have to make decisions about how to deal with the progression of the disease of a child affected by Duchenne Muscular Dystrophy. First, we used an outranking multicriteria method to select among the possible parameters of muscle fatigue evaluation the subset that provide more reliable information, than we used the selected parameters as membership functions for the fuzzy classifier. The output of the fuzzy classifier consisted of three classes: 1-"close to normal results", 2-"results compatible with moderate pathological conditions", and 3-"results congruent with severe pathological conditions". A first test of the classifier was performed using the data of the twenty examinations of six children and it provided good results. We believe that these results are relevant to the clinical applications and they can be easily extended to different pathologies. PMID- 17282727 TI - Preliminary study for gait phases detection to develop a rehabilitation equipment for hemiplegic patients. AB - Preliminary experiment for analyzing weight shift during gait phases for hemiplegic patients was carried out to develop rehabilitation equipment. A gait phase detection system using pressure sensors was developed and the experiment was carried out for eight hemiplegic patients and normal adult. The weight shift during gait phases for a normal adult showed symmetrical for left and right footing phase, but that for the hemiplegic patients showed asymmetrical footing phase. However, it gave sufficient information to discriminate between left and right footing phases. PMID- 17282728 TI - A decision support system for breast cancer treatment based on data mining technologies and clinical practice guidelines. AB - Evidence based medicine is the clinical practice that uses medical data and proof in order to make efficient decisions in the field of the medical domain. Information technology services play a crucial role in exploiting the huge size of medical data involved. Furthermore health care society nowadays utilizes clinical guidelines [1][2] as a new assistant in their efforts to improve clinical decision efficacy. Clinical guidelines provide for the decrease of variance in medical decision making, leading to an improvement of clinical outcome. Therefore this paper focus is twofold. Improving the provision and visualization of disease specific, clinical data, providing for it's faster and more efficient use[l0], while making sure that consistency appears in the clinical practice by importing clinical guidelines in decision support systems. PMID- 17282729 TI - Network architecture for global biomedical monitoring service. AB - Most of the patients who are in hospitals and, increasingly, patients controlled remotely from their homes, at-home monitoring, are continuously monitored in order to control their evolution. The medical devices used up to now, force the sanitary staff to go to the patients' room to control the biosignals that are being monitored, although in many cases, patients are in perfect conditions. If patient is at home, it is he or she who has to go to the hospital to take the record of the monitored signal. New wireless technologies, such as BlueTooth and WLAN, make possible the deployment of systems that allow the display and storage of those signals in any place where the hospital intranet is accessible. In that way, unnecessary displacements are avoided. This paper presents a network architecture that allows the identification of the biosignal acquisition device as IP network nodes. The system is based on a TCP/IP architecture which is scalable and avoids the deployment of a specific purpose network. PMID- 17282730 TI - Wearable Systems for Service based on Physiological Signals. AB - Many researches for useful status information on humans have been done using the bio-signals. The bio-signal acquisition systems can be used to connect a user and a ubiquitous computing environment. The ubiquitous computing environment has to give various services anywhere, anytime. Consequently, ubiquitous computing requires new technology, such as a new user interface, dynamic service mechanism based on context and mobility support, which is different from technology used in desktop environment. To do this, we developed a wearable system, which can sense physiological data, determine emotional status and execute service based on the emotion. In this paper, we described wearable systems for personalized service based on physiological signals. The wearable system is composed of three subsystems, the physiological data sensing subsystem, the human status awareness subsystem and the service management subsystem. The physiological data sensing subsystem senses PPG, GSR and SKT signals from the data glove and sends the data to a wearable system using Bluetooth. The human status awareness subsystem in the wearable system receives the data from bio-sensors and determines emotional status using nonlinear mapping and rule-base. After determining emotion, the service management subsystem activates proper service automatically, and the service management subsystem can provide personalized service for users based on acquired bio-signals. Also, we presented various feature extraction using bio signals such as PPG, GSR, SKT considering mobility, and emotion recognition of human status for the ubiquitous computing service. PMID- 17282731 TI - The Trauma Patient Tracking System: implementing a wireless monitoring infrastructure for emergency response. AB - In mass trauma situations, emergency personnel are challenged with the task of prioritizing the care of many injured victims. We propose a trauma patient tracking system (TPTS) where first-responders tag all patients with a wireless monitoring device that continuously reports the location of each patient. The system can be used not only to prioritize patient care, but also to determine the time taken for each patient to receive treatment. This is important in training emergency personnel and in identifying bottlenecks in the disaster response process. In situations where biochemical agents are involved, a TPTS may be employed to determine sites of cross-contamination. In order to track patient location in both outdoor and indoor environments, we employ both Global Positioning System (GPS) and Television/ Radio Frequency (TVRF) technologies. Each patient tag employs IEEE 802.11 (Wi-Fi)/TCP/IP networking to communicate with a central server via any available Wi-Fi basestation. A key component to increase TPTS fault-tolerance is a mobile Wi-Fi basestation that employs redundant Internet connectivity to ensure that tags at the disaster scene can send information to the central server even when local infrastructure is unavailable for use. We demonstrate the robustness of the system in tracking multiple patients in a simulated trauma situation in an urban environment. PMID- 17282732 TI - Classification of daily physical activities from a single kinematic sensor. AB - This work was conducted in TIMC laboratory to develop methods able to monitor physical activities. In the framework of Health Smart Home, the purpose is to maintain and supervise elderly or fragile people at home. Activity and autonomy levels are important criteria to evaluate the health of the patient. The time spent in each postural state (lying, sitting, standing), the periods of walking and the number of postural transitions: sit-to-stand (StS), back-to-sit (BtS) give information about the patient's activity. The purpose of the current study is to detect these activities using an unique sensor made of three accelerometers, attached to the chest. First, this paper describes how each algorithm (posture, walk, postural transitions) works. Secondly, the results on real data are shown. An experiment with elderly subjects was carried out. Each subject performed daily activities (walking, sitting, lying down, ...) while wearing the sensor. PMID- 17282733 TI - An Ultra-low-power Medium Access Control Protocol for Body Sensor Network. AB - In this paper, a medium access control (MAC) protocol designed for Body Sensor Network (BSN-MAC) is proposed. BSN-MAC is an adaptive, feedback-based and IEEE 802.15.4-compatible MAC protocol. Due to the traffic coupling and sensor diversity characteristics of BSNs, common MAC protocols can not satisfy the unique requirements of the biomedical sensors in BSN. BSN-MAC exploits the feedback information from the deployed sensors to form a closed-loop control of the MAC parameters. A control algorithm is proposed to enable the BSN coordinator to adjust parameters of the IEEE 802.15.4 superframe to achieve both energy efficiency and low latency on energy critical nodes. We evaluate the performance of BSN-MAC using energy efficiency as the primary metric. PMID- 17282734 TI - Physiological signal based entity authentication for body area sensor networks and mobile healthcare systems. AB - With the evolution of m-Health, an increasing number of biomedical sensors will be worn on or implanted in an individual in the future for the monitoring, diagnosis, and treatment of diseases. For the optimization of resources, it is therefore necessary to investigate how to interconnect these sensors in a wireless body area network, wherein security of private data transmission is always a major concern. This paper proposes a novel solution to tackle the problem of entity authentication in body area sensor network (BASN) for m-Health. Physiological signals detected by biomedical sensors have dual functions: (1) for a specific medical application, and (2) for sensors in the same BASN to recognize each other by biometrics. A feasibility study of proposed entity authentication scheme was carried out on 12 healthy individuals, each with 2 channels of photoplethysmogram (PPG) captured simultaneously at different parts of the body. The beat-to-beat heartbeat interval is used as a biometric characteristic to generate identity of the individual. The results of statistical analysis suggest that it is a possible biometric feature for the entity authentication of BASN. PMID- 17282735 TI - An Improved Method for Discriminating ECG Signals using Typical Nonlinear Dynamic Parameters and Recurrence Quantification Analysis in Cardiac Disease Therapy. AB - The discrimination of ECG signals using nonlinear dynamic parameters is of crucial importance in the cardiac disease therapy and chaos control for arrhythmia defibrillation in the cardiac system. However, the discrimination results of previous studies using features such as maximal Lyapunov exponent (λmax) and correlation dimension (D2) alone are somewhat limited in recognition rate. In this paper, improved methods for computing λmaxand D2are purposed. Another parameter from recurrence quantification analysis is incorporated to the new multi-feature Bayesian classifier with λmaxand D2so as to improve the discrimination power. Experimental results have verified the prediction using Fisher discriminant that the maximal vertical line length (Vmax) from recurrence quantification analysis is the best to distinguish different ECG classes. Experimental results using the MIT-BIH Arrhythmia Database show improved and excellent overall accuracy (96.3%), average sensitivity (96.3%) and average specificity (98.15%) for discriminating sinus, premature ventricular contraction and ventricular flutter signals. PMID- 17282736 TI - Association of the spectral features of heart period signal with SNP of NOS in the Chinese Han nationality population. AB - To explore association of the spectral features of heart period signal with SNPs at 5 sites of NOS gene in the subjects (male89, female77, aged 62.40+/-2.5 yrs) by allele specific primer PCR technique. It was found that the TT allelic genotype of NOS2 C-1173T associated with the highest RPH and TT allelic genotype of NOS3 G894T associated with the highest APH in HPS spectral parameters. This suggests the SNPs of NOS2 C-1173T and NOS3 G894T may be the deep layer factors to result in the variability of HPS spectral parameters. PMID- 17282737 TI - On Spectral Analysis of Heart Rate Variability during Very Slow Yogic Breathing. AB - Very slow yogic breathing techniques provide valuable insights into mechanisms of autonomous nervous system regulation that are usually not available for human subjects. This paper presents results of eight sessions of Nadi Shodhana Pranayama practiced at rate of one breath per minute. We characterized statistic and spectral measures of heart rate variability before, during, and after exercises. Significant changes include increase of VLF frequencies caused by slow breathing and decrease in average interbeat interval from 959.3 to 904.1 ms (t(7) = -7.5, p<0.001). We present the results of HRV analysis and analyze origins of characteristic frequency components. The most prominent changes of the exercise include significant increase of respiratory sinus arrhythmia (RSA) and LF/HF ratio, and decrease of breathing frequency after the exercise against the state before the exercise. The maximum LF frequency decreased from 0.0919 Hz to 0.07125 Hz (t(7) = -3.255, p < 0.01), indicating the decrease of average breathing rhythm from 5.5 breaths/min to 4.3 breaths/min. In addition, the state after the exercise is characterized by disappearance of VLF frequencies from the spectrum, and a significant increase of LF/HF from 14.33 to 50.93 (t(7) = 2.461, p <.05). PMID- 17282738 TI - Heart rate control during treadmill exercise. AB - A computer-controlled treadmill and related data collection and processing systems have been developed for the control of heart rate during treadmill exercise. Minimizing deviations of heart rate from a preset profile is achieved by controlling the speed and/or the gradient of the treadmill. A simple and practical heart rate measurement algorithm has been developed to robustly measure the variations of heart rate. Both conventional Proportional-Integral-Derivative (PID) control and fuzzy Proportional-Integral (PI) control approaches have been employed for the controller design. The fuzzy Proportional-Integral algorithm achieved better heart rate tracking performance. Finally, a heart rate based exercising protocol was successfully implemented on the newly designed exercise system. PMID- 17282740 TI - Ensemble based data fusion for early diagnosis of Alzheimer's disease. AB - We describe an ensemble of classifiers based data fusion approach to combine information from two sources, believed to contain complimentary information, for early diagnosis of Alzheimer's disease. Specifically, we use the event related potentials recorded from the Pz and Cz electrodes of the EEG, which are further analyzed using multiresolution wavelet analysis. The proposed data fusion approach includes generating multiple classifiers trained with strategically selected subsets of the training data from each source, which are then combined through a weighted majority voting. Several factors set this study apart from similar prior efforts: we use a larger cohort, specifically target early diagnosis of the disease, use an ensemble based approach rather then a single classifier, and most importantly, we combine information from multiple sources, rather then using a single modality. We present promising results obtained from the first 35 (of 80) patients whose data are analyzed thus far. PMID- 17282739 TI - Beat-to-beat Adaptation of QT Interval to Heart Rate. AB - An adaptive approach is presented to investigate the QT interval response to heart rate variations on a beat-to-beat basis. The relationship between the QT interval and the RR interval is modelled by considering a time-variant system composed of a linear filter followed by a zero-memory nonlinearity approximated by a Taylor expansion. The linear portion describes the influence of previous RR intervals on each QT measurement, while the nonlinear portion expresses how the QT values evolve as a function of the averaged RR measurement at the output of the linear filter. For identification of the unknown system, a Kalman-based procedure is developed that simultaneously estimates all the parameters of the global system. The methodology has been first tested over artificially generated data, showing very good agreement between estimated and theoretical values. Results on data measured over real ECG recordings confirm that the QT interval response is delayed with respect to the RR interval, specially for decelerating heart rate changes. It is also shown that the beat-to-beat evolution of the nonlinearity coefficients is considerably altered when abrupt rate variations occur. PMID- 17282741 TI - Long-term EEG monitoring in the Neonatal Intensive Care Unit. AB - Access, in neonatal intensive care units, to neurological monitoring facilities is often limited by the availability of expensive equipment, expert technicians to provide the biomedical support and neurologists, with neonatal experience, to interpret the data. EEG bedside monitoring is now available through the development of low cost portable bedside monitors. This paper discusses the clinical use of one of those monitors: the BRM2, manufactured by Brainz Instruments. A neonatal nurse can apply the electrodes and bedside interpretation is facilitated through an easily operated touch screen. Digital records can also be transferred to a remote expert for further reviewing. The availability of these devices should complement existing monitoring methods and lead to more efficient diagnosis and prognosis of neurological conditions in the neonatal intensive care unit. PMID- 17282742 TI - A Neuro-behavioral Test and Algorithms for Screening and Evaluating Therapy in ADHD. AB - A new neuro-behavioral test with analysis algorithms has been developed for use in screening individuals for attention deficit hyperactivity disorder (ADHD) and for the quantitative evaluation of ADHD medication/therapy in diagnosed patients. This technique combines a 15 minute auditory-based test of attention with simultaneous EEG monitoring by a wireless, portable data acquisition device. This system acquires both behavioral response (i.e., reaction times to target stimuli, as well as errors of omission/commission) and EEG waveforms. All of the data is simultaneously processed by the algorithms to produce several representative indices. These indices are then combined to produce an overall neuro-behavioral index that represents the degree by which both "behavioral" and "EEG" attention is maintained throughout the test. This test was administered to 5 normal adolescents, and 5 aged-matched children with ADHD who were tested immediately before and one hour after their daily intake of ADHD medication. Both EEG-based and behavioral-response indices were statistically different in ADHD (before medication) compared with normal children. Furthermore, these indices showed an improvement after ADHD medication (values closer to those from normal children). Finally, the combined neuro-behavioral index was significantly more discriminating (normal vs pre-medication ADHD) and sensitive to medication than the indices solely based on EEG or behavioral response alone. PMID- 17282743 TI - Biopattern analysis and subject-specific diagnosis and care of dementia. AB - Worldwide, the number of people that develop Alzheimer's disease and other types of dementia is rapidly rising and will create a considerable financial burden on the health and social services. The availability of new drugs that may slow or even halt the disease progression makes accurate early detection crucial. Objective methods are needed to support clinical diagnosis and care for patients; to quantify severity, monitor progression and response to new treatments. Electrophysiological markers have an important role to play in the objective assessment and care for dementia. The EEG provides a measure of brain dysfunction and EEG changes could be detected fairly early in the dementing process. Subject specific EEG analysis offers the possibility of using objective methods to assess and care for dementia on an individual basis. The main objectives of this paper are: (i) to introduce the concepts of subject-specific EEG analysis as a basis for improving diagnosis and care for dementia; and (ii) present two novel methods for deriving suitable subject-specific electrophysiological markers analysis of fractal dimension and zero crossing interval density of the EEG. We present findings that indicate that the methods are potentially good candidates for the development of individualized, low-cost, easy to administer and reasonably accurate methods for detecting dementia within the growing at risk population. PMID- 17282744 TI - Boosting based classification of event related potentials for early diagnosis of Alzheimer's disease. AB - With the number of the elderly population affected by Alzheimer's disease (AD) rising, the need to find an accurate, inexpensive and non-intrusive procedure that can be made available to community healthcare providers for early diagnosis of Alzheimer's disease is becoming more and more urgent as a major health concern. Several recent studies have looked at analyzing electroencephalogram signals through the use of wavelets and neural networks. In this study, multiresolution wavelet analysis, coupled with the ensemble of classifiers based boosting algorithm is used on the P300 component of the event related potentials (ERP) to determine the feasibility of the approach as a diagnostic tool for early diagnosis of AD. The technique and its promising initial results are presented. PMID- 17282745 TI - Assessing Auditory Discrimination Skill of Malay Children Using Computer-based Method. AB - The purpose of this paper is to investigate the auditory discrimination skill of Malay children using computer-based method. Currently, most of the auditory discrimination assessments are conducted manually by Speech-Language Pathologist. These conventional tests are actually general tests of sound discrimination, which do not reflect the client's specific speech sound errors. Thus, we propose computer-based Malay auditory discrimination test to automate the whole process of assessment as well as to customize the test according to the specific speech error sounds of the client. The ability in discriminating voiced and unvoiced Malay speech sounds was studied for the Malay children aged between 7 and 10 years old. The study showed no major difficulty for the children in discriminating the Malay speech sounds except differentiating /g/-/k/ sounds. Averagely the children of 7 years old failed to discriminate /g/-/k/ sounds. PMID- 17282746 TI - Wireless brain monitoring in the emergency department. AB - Most hospitals in the world do not perform electroencephalograms in the emergency departments due to space, cost, training, and complexity of the equipment and the test. New miniature, low-cost, simple, digital, wireless EEG machines have been developed that solve all four of these inhibiting factors to allow EEG, to be used in emergency departments to evaluate patients presenting with altered mental status for nonconvulsive seizures. Four-channel wireless EEG used in the ED is feasible, provides good quality screening EEGs, and was able to diagnose underlying seizures or slowing in a significant number of patients. PMID- 17282747 TI - Glycemic control in critically ill patients effect of delay in insulin administration. AB - Several recent studies have established a correlation between tight glucose control and decreased perioperative morbidity and mortality in surgical and critically ill patients. We hypothesize that a progressive increase in delay in implementing insulin infusion rate changes would result in a progressively longer time to target glucose level and a progressive decrease in the percentage of time spent within a target glucose range. We formulate a mathematical model of glucose insulin regulation, validate it with patient data, and use it to conclude that progressive delays in implementing insulin infusion rates result in a progressively longer time to target and poorer glycemic control in all three simulated patient types (Normal, Type 1 and Type 2 Diabetes Mellitus). PMID- 17282749 TI - Gastric Impedance Spectroscopy in Cardiovascular Surgery Patients vs. Healthy Volunteers. AB - Impedance spectroscopy has been proposed as a method of monitoring mucosal injury due to hypoperfusion and ischemia in the critically ill. The present study evaluates spectral differences in elective cardiovascular surgery patients compared with the impedance spectra of the gastric mucosa in healthy adults. An impedance spectroscopy probe and nasogastric tube (ISP/NGT) was placed into the stomach of 77 heart surgery and 21 healthy volunteers. The recorded impedance spectra were classified into 3 groups: group 1 for healthy volunteers; group 2 for patients with neither ischemia nor complications; and group 3 for patients with ischemia and complications during the first 3 days in the recovery unit. There were statistical differences in resistance (p<0.001) and reactance (p<0.001) among the 3 groups. The results show that impedance spectra are distinct and significantly different in patients with probable ischemic mucosal injury compared to healthy subjects, and therefore this technology may be a useful prognostic and diagnostic monitoring tool. PMID- 17282748 TI - The quartz crystal microbalance as a microviscometer for improved rehabilitation therapy of dysphagic patients. AB - The viscosity of non-solid foods, and the stability of their viscosity over time, temperature change and shearing is critical in managing dysphagia. The starch based foodstuffs thickeners used in dysphagia therapy are highly non-Newtonian and their viscosity is dependent on shear rate, shear history, temperature and time. This inherently results in the subjective measurement of viscosity and hence the management of dysphagia to be error prone. Given the ageing population, this problem is likely to become more widespread. This paper identifies the need for an objective measurement device rather than the current subjective methods. The use of the quartz crystal microbalance (QCM) as a viscometer for the starch based thickeners is reported. PMID- 17282750 TI - Analysis of pain and blood volume in capillary blood sampling on finger and arm. AB - Alternative site capillary blood sampling may be a useful way to reduce pain during skin puncture. The present study made quantitative measurement of pain and blood volume for both finger and arm sampling in 58 normal female subjects. Visual pain measures resulted in 1/5~1/3 pain scores for arm relative to finger sampling. Deeper puncture thru skin on arm caused more pain to some degree. 399/464 samples from arm were larger than 0.5muL of blood volume. Modern glucose meters require 0.3~0.5muL of capillary blood for test, thus the success rate of blood sugar test was estimated to be 86%. Since daily sampling on finger could cause serious stress for the diabetes due to pain, arm sampling may be a good alternative. However, resampling followed by test failure should be considered. PMID- 17282751 TI - A statistical approach for robust polyp detection in CT colonography. AB - In this paper we describe the development of a computationally efficient computer aided detection (CAD) algorithm based on the statistical features derived from the local colonic surface that are used for the detection of colonic polyps in computed tomography (CT) colonography. The candidate surface voxels were detected and clustered using the surface normal intersection, convexity test, region growing and Hough Transform. The main objective of this paper is the selection of the statistical features that optimally capture the convexity of the candidate surface and consequently provide a high discrimination between local surfaces defined by polyps and folds. The developed polyp detection scheme is computationally efficient (typically takes 3.9 minute per dataset) and shows 100% sensitivity for phantom polyps greater than 5mm and 87.5% sensitivity for real polyps greater than 5mm with an average of 4.05 false positives per dataset. PMID- 17282752 TI - Automated Vertebra Detection and Segmentation from the Whole Spine MR Images. AB - Our algorithm contains two major steps: the intervertebral disk localization step, and the vertebra detection and segmentation step. In the first step, we apply a model-based searching method to approximately locate all the intervertebral disk clues between adjacent vertebrae of the whole spine and the best slice selection. A new approach using an intensity profile on a polynomial function for fitting all these disk clues on the best slice is then used to refine the disk search process. Vertebra centers are detected, and initial boundaries are extracted in the second step. The initial test of the algorithm on the five sets of 7 sagittal slices locates all 23 intervertebral disk centers for the best slice of all five sets. For the evaluation of the boundary extraction of 22 vertebrae, our algorithm successfully locates 100%, 96.6%, 93.2%, 95.5%, 87.5% vertebra corners in image set No.1, 2, 3, 4, and 5, respectively. PMID- 17282753 TI - Automated recursive segmentation of large neocortical images using standard deviation as termination criteria. AB - In this paper we present an improved segmentation algorithm that recursively explores various thresholding levels until it reaches a termination criteria. This segmentation algorithm is based on earlier work adapting Otsu's thresholding approach to myelinated bundles of axons in cortical tissue. Experimentation using over 120 images has confirmed that this termination criteria provides visibly acceptable segmentation in an automated fashion. PMID- 17282754 TI - Segmentation of Opacified Thorax Vessels using Model-driven Active Contour. AB - We propose a novel method, guided slice marching to segment opacified vessels tree in 3D image sets (CT scans). It combines a front propagation technique, slice marching, and an anatomical model to guide the propagation for solving the particular case of touching vessels. The formulation of this method, which is based on interface evolution theory, enables easy integration of an a priori model of knowledge of vessels topology to handle the case of touching vessels, where image-based method systematically fails. The a priori knowledge is expressed as parametric curves that model vessels centerline. That information is injected in the fast marching method through the speed of propagation, setting it to zero at missing vessels boundaries. The model is intended to be reused across patients, and must therefore be registered with the image. PMID- 17282755 TI - Finite element modeling of human head from MRI. AB - The FEM geometry modeling of realistic head is a key issue for the research on FEM-based EEG/MEG. In this paper, a methodology is developed to construct this kind of model. By using this method, a five-layer realistic head FEM model is obtained, and with its application in FEM-based EEG, a satisfying result shows the reliability of the model. PMID- 17282756 TI - A Model-based Algorithm for Mass Segmentation in Mammograms. AB - A novel mass segmentation algorithm is proposed in this paper. It establishes two mass models to represent the various masses, uses iterative thresholding to extract the suspicious area, and applies a DWT-based approach to locate the masses. And then, a region growing process restricted by Canny edge detection is carried out to extract the rough mass regions, and finally active contour model is used to segment the masses accurately. The clinical experiment has demonstrated that our algorithm has higher performance than conventional methods. PMID- 17282757 TI - Interactive multimodal biofeedback for task-oriented neural rehabilitation. AB - Previous studies have suggested that task-oriented biofeedback training may be effective for functional motor improvement. The purpose of this project was to design an interactive, multimodal biofeedback system for the task-oriented training of goal-directed reaching. The central controller, based on a user context model, identifies the state of task performance using multisensing data and provides augmented feedback, through interactive 3D graphics and music, to encourage the patients' self-regulation and performance of the task. The design allows stroke patients to train with functional tasks, and receive real-time performance evaluation through successful processing of multimodal sensory feedback. In addition, the environment and training task is customizable. Overall, the system delivers an engaging training experience. Preliminary results of a pilot study involving stroke patients demonstrate the potential of the system to improve patients' reaching performance. PMID- 17282758 TI - Experimental studies on the training of postural control using an unstable platform. AB - We performed experimental studies on the training of postural control using a training system which consists of an unstable platform, a computer, a computer interface, a monitoring device, and training programs. Using this system with the training programs that we have developed, we performed a variety of experiments of training the abilities of postural control of subjects. To evaluate the effects of the training, the parameters on how long a subject can maintain a focus on a target, the mean absolute deviation of the trace, and the fatigue of the muscles in lower limbs were measured. The experimental results showed that the training system can improve the ability of postural control of the subject. Therefore, the training system could be applied to clinical rehabilitation training for posture control as a new balance training system. PMID- 17282759 TI - Human interface and transmit frequency control for the through-air acoustic real time high resolution vision substitute system. AB - Existing vision substitute systems are not useful as navigation system due to the limitation of spatial and time resolution. In this study we propose a transmit control method free from range aliasing for a high resolution acoustic vision substitute systems, which we previously proposed. We also examine a human-machine information transfer method with a vibrotactile stimulator array consisting of 13 × 21 elements. It presents the target area of 30 degree × 60 degree by the sampling interval of 1 degree at the center. The system presents range, direction, and surface topography of targets to the subject. PMID- 17282760 TI - Development of a neurocognitive remediation system by virtual reality. AB - This paper presents a system developed for cognitive impairment evaluation and training. We integrate three different test modules in the system for decreasing the complexity of the system manipulation and increasing the completeness of various cognitive function evaluations. Besides the standard modules, including CPT and WCST, a new module to evaluate and train the cognitive ability in the three dimensional space is also developed by using the virtual reality technique. Therefore the system can improve the incompleteness of 2D shape design in the standard test and assist the physiotherapist to evaluate the patient's ability to recognize the object not only in two dimensions but also in three dimensions. PMID- 17282761 TI - Development of on-bed lower extremity exercise system for use with networked virtual space. AB - A virtual space locomotion interface device using lower limb motion at supine position has been developed to allow the users to exercise and communicate each other at home. The velocity control performance, muscle activity and the energy consumption while using the developed device were evaluated. It was demonstrated that the developed device reflects the user's subjectivity adequately and the virtual space walking distance is to be set as three times of the actual distance to obtain the same exercise effect. PMID- 17282762 TI - The development of a new training system for improving equilibrium sense using a virtual bicycle simulator. AB - In this paper, a new rehabilitation training system was developed to improve equilibrium sense control by combining virtual reality technology with a fixed exercise bicycle. In order to evaluate the effectiveness of the training system, twenty normal healthy adults participated as test subjects in the investigation of the influence of different the parameters on equilibrium sensory control. Several factors including path deviation, cycling time, cycling velocity, center of pressure were evaluated and analyzed quantitatively. Also, we investigated the usefulness of virtual feedback information for weight shift on the improvement of the effect of equilibrium training. After conducting repeated tests, we found improvements not only in of the ability to controlling balance and weight shift but also in the overall cycling capabilities such as cycling speed. Therefore, the new training system utilizing an excise bike and a virtual reality system is found to be effective on the improvement of equilibrium sense, and the technology we have developed seems to have a good prospect in the rehabilitation field. PMID- 17282763 TI - Apnea detection based on time delay neural network. AB - Sleep apnea syndrome (SAS) is a very common sleep disorder disease. Reliable detection of apnea is very crucial for subsequent treatment. In this article, a novel method based on artificial neural network is proposed for such purpose. With its time-invariant property the time delay neural network (TDNN) is adopted in this system to employ the temporal trend of apnea event. As airflow and SaO2 take the most important roles in sleep apnea syndrome diagnosis, features extracted from both of them are simultaneously fed into the neural network. The proposed algorithm was tested with 15 overnight polysomnographic (PSG) records, and with a sensitivity rate of 90.7% and 80.8%, a specificity rate of 86.4% and 81.4% for apnea and hypopnea detection, respectively. Furthermore, the proposed algorithm can accommodate in some manner the airflow sensor failure due to technical errors. But, as the SaO2 changes are commonly delayed by 10 or more seconds compared to the airflow signal, integration of SaO2 make this method only suited for offline detection. In conclusion, systems based on this algorithm can be used as a valuable timesaving adjunct for PSG SAS diagnosis. PMID- 17282764 TI - Nocturnal cardio-respiratory indices - a novel screening tool for pediatric obstructive sleep disordered breathing. AB - Obstructive sleep apnea (OSA) is a common breathing disorder among children with a prevalence estimated at 2-4%. Electrocardiography (ECG) based signal processing, especially heart rate analysis, demonstrated its promising future as both an alternative to other expensive portable sleep study methods and additional approach to sleep cardio-respiratory autonomic interactions which the current clinical standard polysomnography (PSG) lacks. A novel strategy was applied on pediatric OSA detection using RR intervals. A sensitivity of 89%, specificity of 96%, positive predictive value of 89%, and negative predictive value of 96% was achieved in case-to-case detection using 37 clinical pediatric full PSG data. PMID- 17282765 TI - Detection of central respiratory events using pulse transit time in infants. AB - The prevalence of sudden infant death syndrome (SIDS) has been well studied and central sleep apnea is deemed as one of the possible causes. Current gold standard for its diagnosis is nocturnal polysomnography (PSG). However, this procedure is complex and generally needs to be performed in a sleep laboratory. Pulse transit time (PTT) shows its potential to indicate abrupt blood pressure (BP) changes during the occurrences of upper airway obstruction. The main objective of this study was to assess the capability of PTT to differentiate central respiratory events from tidal breathing in infants. This study involved 5 infants (4 male) with mean age of 7.8 months. 50 valid central respiratory events were randomly selected. These events were free from motion artifacts and pre scored in the corresponding PSG studies by two blinded observers. PTT measurements from these events were then evaluated against the PSG scorings. Using a two-tailed F-test for variance, it was observed that central events differed from tidal breathing in a significant manner (p<0.05). Furthermore, PTT has showed its sensitivity to monitor marginal BP fluctuations during tidal breathing. Hence, the results herein suggest that PTT can be a valuable non invasive technique to monitor central apneic events in sleeping infants. PMID- 17282766 TI - Variability of snore parameters in time and frequency domains in snoring subjects with and without Obstructive Sleep Apnea. AB - Several studies have shown differences in spectral parameters between simple snorers and patients with Obstructive Sleep Apnea Syndrome (OSAS). Most of them analyzed a reduced number of snores and/or only post-apneic snores were selected in OSAS patients. Previous findings suggest that snore parameters have a greater variability as the severity of OSAS increases. In this work we propose to analyze the snoring variability through the magnitude of the first difference of snore parameters. The technique is applied to long time sound recordings from 9 simple snorers (15795 snores) and 15 OSAS patients (19263 snores). The snores are characterized by their sound intensity an by a set of spectral parameters The variability of snore parameters is well correlated to OSAS severity (r>0.7) and is significantly greater in OSAS patients than in simple snorers (p<0.005). The results are similar when post-apneic snores are excluded from the analysis. Snoring subjects are classified with a logistic regression model, which is validated with the live-one-out method. The model is adjusted to correctly classify 100% of OSAS patients for screening purposes previously to enroll for a whole polysomnographic study. PMID- 17282767 TI - Image-based three-dimensional finite element modeling approach for upper airway mechanics. AB - The goal of the project is to investigate new computational tools for understanding normal upper airway mechanics and the pathophysiology of obstructive sleep apnea (OSA), a disorder characterized by repetitive pharyngeal collapse and occlusion during sleep. To relate the airway mechanical parameters to anatomy, and explore the roles of primary muscle properties, airway shape and structure, a new computational system for modeling of rat upper airway passive mechanics based on magnetic resonance imaging (MRI) was developed. The model is capable of computing stress and strain distributions under arbitrary loading, and dynamic animation of three-dimensional airway motion. PMID- 17282768 TI - Analysis of sleep fragmentation and sleep structure in patients with sleep apnea and normal volunteers. AB - Sleep disorders have a high prevalence. Sleep disorders are recognized first by the complaint of nonrestorative sleep. A quantification of the disorder is done by the investigation in a sleep laboratory. The investigation in the sleep laboratory examines the EEG, EOG and EMG to derive sleep stages. This is a labor intensive sleep scoring after the polysomnography investigation. Usually the time course of the sleep stages is quantified in terms of percentages of stages related to total sleep time and the latencies for the individual stages. The additional feature of transitions between sleep stages and the disruption of sleep, which corresponds to periods of wakefulness during sleep are not evaluated systematically. We have evaluated these transitions using a statistical approach. We have detected systematic differences in the distributions o sleep stages and wake states during sleep. This differences were investigates in normal subjects and patients with sleep apnea. Then these differences were investigated in different species. The difference in the distributions can be explained only by fundamentally different regulation of sleep and wakefulness. PMID- 17282769 TI - Improving Prediction of Residue Solvent Accessibility with SVR and Multiple Sequence Alignment Profile. AB - A new method based on support vector regression (SVR) has been introduced to predict the relative solvent accessibility (RSA) of residues from protein primary sequences, which uses the local information of protein primary sequences as input. Different to most previous methods which are designed to predict the exposure state (exposed/buried, exposed/intermediate/buried, etc) of a particular residue according to its relative solvent accessibility, this method predicts the real value of RSA, by which more information about residue location in protein 3D structure can be retained than state assignment. Measurements for prediction performance, i.e. the mean absolute error (MAE) and correlation coefficient (CC), were compared with a former RVP-Net method, which was based on a multilayer feed forward neural network. With 3-fold cross validation test, the MAE and CC of the SVR method for all data sets were consistently better than those obtained by the RVP-Net. In addition, we used the profile of multiple sequence alignment as input and achieved a significant improvement in prediction performance comparing with using only single sequence information. The final prediction result on the CB-513 data set by our method was 16.8% for MAE and 0.562 for CC. The results demonstrate that SVR is a useful tool for protein sequence analyses. PMID- 17282770 TI - UMass Morph Server: Macromolecular Dynamics Analyses Using Elastic Network Models. AB - The geometry-based mechanical models called elastic network models (ENMs) in various resolutions have been developed for the study of macromolecular motions. In a coarse-grained ENM, a biological system is represented as a network of springs connecting representative points. They range from single atoms to functional domains depending on the level of details in modeling. In this paper presented are the various kinds of coarse-graining methods such as symmetry constrained, rigid-cluster, and hybrid ENMs. They enable us to overcome the computational burden and memory limitation in the conventional molecular dynamics (MD) simulations and full-atom normal mode analysis (NMA) without loss of generality. For the broad impact of this work on the structural biology area we also develop the UMass Morph Server (UMMS). Based on the requests from online users, UMMS does not only serve a harmonic NMA that describes thermal behaviors (i.e., fluctuations) of a macromolecule around its equilibrium state, but also generates anharmonic transition pathways between two end conformations by using the elastic network interpolation (ENI) also developed by the author. In addition, UMMS can provide two unique features as follows: (i) interpretation of massive MD data by finding essential pathways (ii) the conformation prediction incorporated with time-resolved information such as FRET data. Many example movies and numeric data can be downloadable at http://biomechanics.ecs.umass.edu/umms.html. PMID- 17282771 TI - Predicting protein secondary structure using continuous wavelet transform and Chou-Fasman method. AB - Secondary structure of a protein can be predicted efficiently by combining continuous wavelet transform (CWT) and Chou-Fasman method. We selected a protein with ID 1gca from PDB database, and substitute every amino acid of the protein with corresponding hydrophobic value. Then CWT was used to get the nucleated residues of certain type of secondary structure. The regions were extended along the protein sequence in each direction based on Chou-Fasman rules. The prediction accuracy for ..-helix, ..-sheet (regular secondary structures), loop (irregular secondary structure) is 80.57%, 75.41%, and 92.31%, respectively. PMID- 17282772 TI - Subdivision approach to target-constrained conformational searching. AB - Conformational searching is common in many applications and algorithmic improvements on either speed or the quality would have a profound impact. In this paper, we address a target-constrained conformational searching problem and show two subdivision methods approximating the solutions rather than solving for the exact solutions. The performance of the methods is presented. PMID- 17282774 TI - Measurement of internal constraints during an interventional radiology procedure. AB - This paper presents a novel method for measurements of internal constraints during an Interventional Radiology procedure. Fiber-optic strain gauge, operating as a Fabry-Perot interferometer, is inserted and navigated inside a polyvinyl alcohol (PVA) model. The information obtained from deformation of the Fabry-Perot cavity is analyzed and the results are then rescaled through a calibration procedure for catheters. The measures help to locate the maximum interaction forces between catheter and blood vessel wall at approximately 1.3 N and to observe the shape of dynamic interaction during manipulation. PMID- 17282773 TI - Structure Based Prediction of Binding Residues on DNA-binding Proteins. AB - Annotation of the functional sites on the surface of a protein has been the subject of many studies. In this regard, the search for attributes and features characterizing these sites is of prime consequence. Here, we present an implementation of a kernel-based machine learning protocol for identifying residues on a DNA-binding protein form the interface with the DNA. Sequence and structural features including solvent accessibility, local composition, net charge and electrostatic potentials are examined. These features are then fed into Support Vector Machines (SVM) to predict the DNA-binding residues on the surface of the protein. In order to compare with published work, we predict binding residues by training on other binding and non-binding residues in the same protein for which we achieved an accuracy of 79%. The sensitivity and specificity are 59% and 89%. We also consider a more realistic approach, predicting the binding residues of proteins entirely withheld from the training set achieving values of 66%, 43% and 81%, respectively. Performances reported here are better than other published results. Moreover, since our protocol does not lean on sequence or structural homology, it can be used to annotate unclassified proteins and more generally to identify novel binding sites with no similarity to the known cases. PMID- 17282775 TI - Surface Modification of Bio-MEMS Micro-device with Conducting Polymer - Studies with Rat Cardiomyocytes. AB - Conducting polymer can modify device surface properties and incorporate biomolecules for immobilization by electropolymerization at the same time. We investigated a method for surface modification by electrochemically deposited polypyrrole onto surface of Bio-MEMS micro device. We reported the effects of the numbers of CV cycle on the deposited film thickness and roughness in this paper. Furthermore, to prepare polypyrrole entrapment biomolecules on micro-device as a cell-culture substrate was demonstrated to promote cells adhesion. PMID- 17282776 TI - Imaging of Regional Differences of Muscle Oxygenation during Exercise Using Spatially Resolved NIRS. AB - The development of imaging systems using near-infrared spectroscopy (NIRS) has enabled noninvasive measurement of regional changes in muscle oxygenation. A spatially resolved NIRS (SR-NIRS) imaging instrument was utilized for real-time measurement of spatial-temporal changes in muscle oxygenation during exercises. Changes in muscle oxygenation and localized O2consumption in the quadriceps muscle were measured during sustained isometric knee extension without and with leg-press to the ground exercises. In the former exercise, the level of tissue oxygen saturation (TOS) of the rectus femoris (RF) muscle was found to be lower than that of vastus lateralis (VL) and vastus medialis (VM) muscles. The highest localized O2consumption rate, VO2, reflecting the localization in distribution of muscle metabolism, was detected in the RF muscle at the initial stage of exercise. As exercise progressed, VO2of the RF muscle decreased whereas that of the VL and VM muscles increased. In contrast, TOS decreased to about the same level for the VL, RF and VM muscles in the latter exercise. Also, VO2of all three muscles decreased as exercise progressed. Initial results demonstrated that the SR-NIRS instrument enables measurement of regional differences in muscle oxygenation in the quadriceps muscle during different exercises. PMID- 17282777 TI - Relation between hematocrit and optical density in pulse oximetry -In vitro study with Waseda mock circulatory system-. AB - Optical properties of living tissues have not been well established even today, and bioopticinstrumentations have to be based on empirical formulae. In order to examine optical properties of the tissue having pulsating blood perfusion, we investigated the relation between optical density (defined as O.D.) of whole blood and hematocrit by transmission spectrophotometry. We used Waseda mock circulatory system that simulates blood circulation in the tissue. It was found that with increasing light path length, O.D. per unit light path length due to scattering and absorption effect, tended to become constant in each hematocrit. For wavelengths of 660, 805 and 940 nm, the relations between O.D. of whole blood and hematocrit predicted by Twersky's equation, Loewinger's equation and photon diffusion equation fitted to the data obtained. Meanwhile, for 1300 nm, the relation predicted by Loewinger's equation gave the best fit to the data. PMID- 17282778 TI - Fluorescent Detection of Oral Pathogens by a Solid-Phase Immunoassay on PDMS. AB - We have developed an array of sensors for the oral pathogen Streptococcus mutans (S. mutans) using an enzymelinked linked immunosorbent assay (ELISA) on a polydimethylsiloxane (PDMS) device. The model bacterial analyte, S. mutans, has been implicated in the initiation and progression of dental caries. The PDMS was modified with 3-aminopropyltriethoxysilance (APTS) and glutaraldehyde to covalently crosslink monoclonal anti-S. mutans immunoglobulin G (IgG) to the sensor surface. Successful IgG immobilization was verified by AFM and fluorescence imaging. Colloidal bacteria were captured on the sensor surface and labeled with immuno-active quantum dots (QDs), whose fluorescence was excited by an LED and detected by a CCD. The system was capable of detecting S. mutans concentrations as low as 6 106cells/ml in a 20 μl sample. This work represents a stable foundation for the development of a chair side diagnostic system capable of specific and sensitive detection of pathogens directly from oral fluid. PMID- 17282779 TI - Development of an optical arterial hematocrit measurement method: pulse hematometry. AB - The blood hematocrit is well recognized as the versatile index of various physiological conditions especially for anemia, polycythemia and dehydration. However, the conventional method of the hematocrit measurement was conducted with the direct blood sampling. In this study, based on the similar principle of the pulse oximetry, a simple principle of optical noninvasive hematocrit measurement method, pulse hematometry, was introduced. And the performance of the optical sensor evaluated with healthy subjects was also reported. Because of its simplicity, the pulse hematometry would be promising technique as patients monitoring and daily healthcare. PMID- 17282780 TI - Noise Analysis of MREIT at 3T and 11T Field Strength. AB - In Magnetic Resonance Electrical Impedance Tomography (MREIT), we measure the induced magnetic flux density inside an imaging object subject to an external injection current. The magnetic flux density is contaminated with noise and this ultimately limits the quality of reconstructed conductivity and current density images. By using two methods to analyze amounts of noise in 3T and 11T MREIT systems, we found that a carefully designed MREIT study will be able to reduce the noise level below 0.1 nT. PMID- 17282781 TI - Detecting Human Head Conductivity Distribution by Means of a RSM- MREIT Algorithm. AB - We have developed a new Magnetic Resonance Electrical Impedance Tomography (MREIT) algorithm, RSM-MREIT. This new algorithm uses Response Surface Methodology (RSM) and Simplex method to reconstruct subject's conductivity distribution. RSM-MREIT algorithm uses only one component of the measured magnetic flux density to reconstruct the conductivity images, and, consequently, solves the rotation problem in MREIT. The proposed algorithm is tested on a three sphere head model and the simulation results suggest that the proposed algorithm can reconstruct the conductivity distribution with high accuracy. PMID- 17282782 TI - Assessment of the Viability of Transplant Organs with 3D Electrical Impedance Tomography. AB - Methods that can determine the extent of tissue damage in transplant organs, before the decision to transplant has been made, have the potential to improve the outcome of the procedure by preventing unfit organs from being transplanted into the patient. The raised confidence in the organ state with such a technique would also increase availability. Now restricted due to the fear of introducing a failed organ resulting from the relative lack of viability data during transport, stringent criteria for donation would relax. Electrical impedance tomography is an imaging modality that recovers the spatial variation of the complex impedivity in the body from electrical measurements made on the periphery. In this study, we apply 3D EIT with the complete electrode model to a sample conductivity distribution that might result from an organ that is losing its viability due to prolonged ischemia. The reconstructed images show that EIT has the potential to become an adjuvant method for the field of organ transplantation. PMID- 17282783 TI - Quasi-polar drive pattern for brain electrical impedance tomography. AB - To seek a single source drive pattern that is more suitable for brain electrical impedance tomography (EIT), a comparison between adjacent, cross, polar and newly proposed quasi-polar drive patterns was made in aspects of boundary voltages dynamic range, independent measurement number, Total boundary voltage changes and anti-noise performance based on an equivalent circuit of the brain resistivity distribution consisting of 7300-odd resistors. The results demonstrate that quasi polar drive pattern is optimal in all the aspects except dynamic range. Polar and cross drive patterns come next, and adjacent drive pattern is the worst. Therefore, the quasi-polar drive pattern should be chosen for brain EIT. PMID- 17282784 TI - MNR Method with Self-Determined Regularization Parameters for Solving Inverse Resistivity Problem. AB - The modified Newton-Raphson (MNR) method is used to solve the inverse resistivity problem in this paper. Using Tikhonov regularization method, comparisons among the L-curve method, the zero-crossing (ZC) method and the generalized cross validation (GCV) method are carried out for determining the regularization parameters of MNR method. By these criterions the appropriate regularization parameters are self-determined and adjusted with the reconstruction iterations. Our simulation experiments on 2D circle model showed that the GCV method can provide the best reconstruction quality with the fastest speed in inverse resistivity problem using MNR method. PMID- 17282785 TI - Modelling for scanning impedance imaging. AB - Scanning electrical impedance imaging (SII) is a previously-introduced high resolution imaging modality with the potential of imaging the electrical activities of biological tissues. In this paper, a detailed complex electrostatic model is derived to describe the physical phenomena of the SII system. This model reveals the relationship between the voltage measurement and impedance distribution and also shows how system parameters such as height affect the resolution of the impedance image. A numerical solution is developed for this model based on the finite difference method (FDM). A variation of classical FDM is used to solve the complicated boundary conditions introduced by the combination of the electrostatic field and the peripheral circuit. Good correspondence can be observed when comparing the model simulation with experimental data acquired during a line-scan. It can be seen that the model provides a good explanation for the experimental results and can assist in the design of the special dual-conductor impedance probe used in the SII system. A two-source improvement for the SII system which is motivated by the modelling work is implemented and the corresponding physical analysis is obtained. It can help the reduction of the current contribution from the shield to the tip so that higher resolution can be achieved. PMID- 17282786 TI - Denoising of MR Tomography Signal with Automatic Adjustment of Time-Variant Thresholds. AB - Removing noise from an free induction decay (FID) signal is of fundamental significance in the analysis of results of magnetic resonance (MR) spectroscopy and tomography. Optimum solution can be seen in removing noise by means of a digital filter bank that uses half-band mirror frequency filters of the type of low-pass and high-pass filters. A filtering method using digital filters and the approach threshold adjustment is described in the paper. PMID- 17282787 TI - Dynamic EEG Analysis via the Variability of Band Relative Intensity Ratio: A Time Frequency Method. AB - The effectiveness of band relative intensity ratio (BRIR) based on Time-Frequency Representations (TFRS) was explored as a method to depict brain dynamics in this paper. Electroencephalographic (EEG) signals from 20 subjects through 16 channels have been studied under open eyes state and closed eyes state. The results indicate that EEG rhythm features and the dynamic process of brain activity can be revealed explicitly though the time-frequency variability and the time frequency- space variability of BRIR. The alpha rhythm is best seen under eyes closed state and blocked when eyes are open generally, but it is strengthened in some times when it is blocked overall under open eyes state. PMID- 17282789 TI - A Method of Recognizing Finger Motion Using Wavelet Transform of Surface EMG Signal. AB - In this paper, an identification method of finger motions using the wavelet transform of multi-channel electromyography (EMG) signal is presented. The first step of this method is to analyze surface EMG signal detected from the subject's upper arm using the multi-resolution of wavelet transform, and extract features using the variance, maximum and mean absolute value of the wavelet coefficients. In this way, a new feature space is established by wavelet coefficients. The second step is to import the feature values into an Artificial Neural Network (ANN) to identify the finger motion. Based on the results of experiments, it is concluded that this method is effective in identification of finger motion. Thus, it provides an alternative approach to use the surface EMG in controlling the finger motion of a multi-fingered prosthetic hand. PMID- 17282788 TI - Based on wavelet transform to analyze rabbit somatosensory evoked potential. AB - Rabbits were narcotized and stimulated by 0.5Hz electric pulse. Potential of scalp was sampled at 3764Hz. Wave components of rabbit somatosensory evoked potential (SEP) can be located precisely through the method of continuous wavelet transform (CWT). Frequency feature of SEP can also be analyzed by CWT. The technique of continuous wavelet transform, which can project a one-dimension signal into a two-dimension time-frequency space, will become a useful method to process medical electronic signal. Key words: wavelet transform, somatosensory evoked potential, single-trial. PMID- 17282790 TI - Self spectrum window method in wigner-ville distribution. AB - Wigner-Ville distribution (WVD) is an important type of time-frequency analysis in biomedical signal processing. The cross-term interference in WVD has a disadvantageous influence on its application. In this research, the Self Spectrum Window (SSW) method was put forward to suppress the cross-term interference, based on the fact that the cross-term and auto-WVD- terms in integral kernel function are orthogonal. With the Self Spectrum Window (SSW) algorithm, a real auto-WVD function was used as a template to cross-correlate with the integral kernel function, and the Short Time Fourier Transform (STFT) spectrum of the signal was used as window function to process the WVD in time-frequency plane. The SSW method was confirmed by computer simulation with good analysis results. Satisfactory time- frequency distribution was obtained. PMID- 17282791 TI - Classification of Schizophrenia and Depression by EEG with ANNs*. AB - The clinical application shows that it is possible to differentiate between patients suffering from schizophrenia, depression and normal healthy persons on the basis of EEG rhythms. This paper describes the application of two artificial neural networks (ANN) approaches, BP ANN and self-organizing competitive ANN for the discrimination of three kinds of subjects (including 10 normal control, 10 schizophrenic patients and 10 depressive patients), with EEG rhythms used as feature vectors. In addition, the comparison between two ANNs is illustrated in this paper. The results show that ANN is an effective approach for discrimination of these three kinds of objects and BP ANN has better comprehensive performance than self-organizing competitive ANN technique in this study. Therefore, the ANN technique could be used as a new tool for computer-aided diagnosis for some psychosis. PMID- 17282792 TI - Phospholamban, a predicted candidate for early cardiac problem detection using signal processing techniques. AB - Heart failure has been identified as a serious international problem, in particular for aging groups, posing both an increasing number of patients on waiting lists in countries susceptible with Medicare systems and increasing financial burdens. It may be imperative to develop a marker that can identify such problems at an early stage. It is believed that certain proteins have crucial roles in early detection of cardiovascular disease, the number one killer in United Arab Emirates. This might be accomplished by recognition of unusual features in protein candidates. Phospholamban (PLB) is a 52 amino acid phosphoprotein which regulates the calcium pump of cardiac sarcoplasmic reticulum (SR). During muscle contraction, PLB inhibits the Ca++ pump. During muscle relaxation, it can be phosphorylated, removing the inhibition and allowing Ca++ to be pumped back into SR. With the calcium pump disrupted, the heart muscle is probably weakened, resulting in congestive heart failure. Interleukin 6 (IL-6) is considered as a better predictor of heart attack in elderly people. It could serve as an early warning sign since its level increases early in the inflammatory process. Also, it has been established that myocyte enhancer factor 2A (MEF2A) plays a vital role in the development of cardiovascular problems like atherosclerosis and restenosis after angioplasty inflammation. In this paper, the resonance recognition method (RRM) has been employed to determine the characteristic frequencies of the above-mentioned proteins. It has been found that phospholamban and IL-6 share the same characteristic frequency, 0.3320 plusmn 0.0002 suggesting their common probable contribution to heart failure. Myocyte enhancer factor 2A does not share the same characteristic frequency. Hence, phospholamban is suggested as a highly probable early marker for cardiac problem detection. PMID- 17282793 TI - Independent component analysis and wavelet decomposition technique for the detection of motor unit action potentials. AB - This paper proposes the use of independent component analysis (ICA) and thresholding estimation calculated in wavelet transform for noise reduction in electromyographic (EMG) signals. In contrast to existing amplitude threshold detection scheme which either need to be participated by the operator or is time consuming, this method is more fast and completely automatic. The ICA is implemented by means of a fast and robust fixed-point algorithm. The basic tool is the method of power spectrum estimation, the Welch method, that allows us to analyze power spectral density of non-stationary signals. PMID- 17282794 TI - ECG Modeling with DFG. AB - ECG signals model described by data flow graph (DFG) is addressed in this paper. The model is built on the time processing. The principle of DFG modeling method for ECG signal is based on the idea of ECG time interval. According to the data processing flow, the each wave could be considered as a piece of ECG signal and the pieces could be processed in time sequence. According to the model, the time characters and parameters could be processed by the algorithm. And the model is also useful for the design of ECG signal generator. PMID- 17282795 TI - EEG model and location in brain when enjoying music. AB - The aim of this study was to confirm the character of EEG and the location in brain when a person was enjoying different rhythm music. It made the subjects excited when they enjoyed different rhythm music, the EEG signals are collected with Phoenix Digital EEG with 128 channels, and compared with the ones before the subjects enjoying the music. Obvious differences have been found between them. And the character of EEG has a little differences when the subjects enjoyed different rhythm music. The character of EEG is 30 Hz when the subjects enjoyed Skating Waltz, the height of wave crest is about 200; the character of EEG is 32 Hz when the subjects enjoyed Radetzy-March, the height of wave crest is about 300 500; the character of EEG is 28 Hz and 38 Hz when the subjects enjoyed Disco music, the height of wave crest is about 200. Then using the software of ASA 3 Course designed by ANT company of Germany, the location in brain was confirmed when a person had excited. The region of the location in brain when a person was excited was focused in the area of the middle abdomen in the pons' side. PMID- 17282796 TI - Noise Reduction in ECG Signal Based on Adaptive Wavelet Transform. AB - Noise always influences on the result of signal-detection, therefore it is a hot topic to detect signal under the low signal-to-noise ratio (SNR) in current detection field. However, it is an intractable problem of signal-detection to extract weak signal under a high noisy environment. Adaptation filter provides a simple and useful way to detect signal. Through measuring and studying, it is possible to carry out the best combination of weak signal under the condition of weak signal. In this paper, we propose a novel mechanism to detect the ECG signal based on adaptation wavelet transform (WT). We adopt the sub-strap coded theory of WT and restore post-combination weak signal through adaptation matching of multi sub-straps' weights. The simulation results show that the proposed method can further improve the ability to detect signal, which is a very effective scheme to detect the property of weak signal and improve SNR. PMID- 17282797 TI - Measurement of spectral maximum shift of ultrasonic backscatter signals in cancellous bone. AB - The feasibility of assessing cancellous bone from the Spectral Maximum Shift (SMS) of the backscattered ultrasonic signal is investigated. And the SMS of backscatter signals from bovine tibiae cancellous bone in vitro were measured and discussed. The spectral maximum of the backscattered signal downshift with increases of the apparent density of cancellous bone. When the bone suffered from osteoporosis, the density will reduce. Therefore, compared with the backscattered signal spectrum in the normal cancellous bone, the osteoporotic cancellous bones have small SMS of backscattered signal. According to the size of SMS, the status of cancellous bone and the degree of osteoporotic fracture risk may be assessed. On the other hand, techniques based on ultrasonic backscatter offer the advantage that only one ultrasonic transducer rather than two transducers is required to perform measurements. The operation of measurement is convenient and simple in assessment of cancellous bone status and diagnosis of osteoporosis. PMID- 17282798 TI - A mixture of experts network structure for EEG signals classification. AB - This paper illustrates the use of mixture of experts (ME) network structure to guide model selection for classification of electroencephalogram (EEG) signals. Expectation-maximization (EM) algorithm was used for training the ME so that the learning process is decoupled in a manner that fits well with the modular structure. The EEG signals were decomposed into time-frequency representations using discrete wavelet transform and statistical features were calculated to depict their distribution. The ME network structure was implemented for classification of the EEG signals using the statistical features as inputs. Three types of EEG signals (EEG signals recorded from healthy volunteers with eyes open, epilepsy patients in the epileptogenic zone during a seizure-free interval, and epilepsy patients during epileptic seizures) were classified with the accuracy of 93.17% by the ME network structure. The ME network structure achieved accuracy rates which were higher than that of the stand-alone neural network models. PMID- 17282799 TI - An Efficient Adaptive Feedback cancellation using by Independent component analysis for hearing aids. AB - In this paper, we proposed a feedback cancellation algorithm based on independent component analysis (ICA) for digital hearing aids. In conventional adaptive feedback cancelling systems, the normalized least mean squares (NLMS) algorithm used to reduce acoustic feedback in which hearing aids occurs, generally at high gains. But primary input signal depend on the acoustic feedback signal in higher order statistics, proposed algorithm was better acoustic feedback cancelling performance than the conventional NLMS algorithm when the input signal has a Laplacian distribution with high-order processing in real-time simulation of TMS320C 6711 DSK. PMID- 17282800 TI - Detection of ECG Signal Based on Multi-resolution Sub-band Filter. AB - A high noisy environment severely contaminates the ECG signal. In this paper, the use of a wavelet transform domain filtering technique as an adaptive de-noising tool, implemented in ECG signal analysis, is presented. The multi-resolution representations of the signal, produced by wavelet transform (WT), are used for signal structure extraction. Experimental results have shown that the implementation of this wavelet-based filter in ECG signal analysis results in an efficient reduction of the high noisy environment, producing an almost noise-free output signal. Due to its simplicity and its fast implementation the method can easily be used in clinical medicine. PMID- 17282801 TI - Time-varying analysis of heart rate variability with kalman smoother algorithm. AB - A time-varying parametric spectrum estimation method for analyzing nonstationary heart rate variability signals is presented. In the method, the nonstationary signal is first modeled with time-varying autoregressive model and the model parameters are estimated recursively with a Kalman smoother algorithm. The spectrum estimates for each time are then obtained from the estimated model parameters. Statistics of the obtained spectrum estimates are derived using the error propagation principle. The obtained spectrum estimates can further be decomposed into separate components and, thus, the time-variation of low and high frequency components of heart rate variability can be examined separately. PMID- 17282802 TI - Extraction of VEP based on third-order correlation based filters and wavelet thresholding denoising method. AB - A new wavelet thresholding function which has continuous derivative was discussed in this research. The wavelet thresholding denoising method and TOC (third-order correlations)-based filtering approach were used in extracting visual evoked potential (VEP). The experimental results showed that the new thresholding function combined with TOC-based filters have good performance in visual evoked potential (VEP) analyzing. PMID- 17282803 TI - Measuring minimum critical flow for normal breath sounds. AB - Relationship between respiratory sounds and flow has always been of interest for researchers and physicians. However, the flow-sound relationship at very low flow rate has been questionable because breath sounds must exceed a minimum flow in order to be audible and different from the background noise. This study aimed to find the minimum critical flow rates for respiratory sounds to be audible and different from background noise. Tracheal and lung sound signals of healthy subjects in two groups of adults (12 subjects) and children (9 subjects) were studied. The values of minimum critical flow were determined comparing the spectrogram of the respiratory sounds at very low flow with that of during breath hold. The values of minimum critical flow for tracheal sounds were found to be 3.7.. 1.7 ml/s/kg and 2.7 .. 1.7 ml/s/kg for adults and children, respectively. The minimum critical flows for lung sounds were found as 6.2 .. 1.8 ml/s/kg and 4.0 .. 2.9 ml/s/kg for adults and children, respectively. PMID- 17282804 TI - Detection of Impedance Cardioaraphy's Characteristic Points Based on Wavelet Transform. AB - With observation that singularities of a multi-scale wavelet transform result are related to discontinuities of the signal, a novel wavelet transform based method is proposed in this paper for detection of biomedical signals' characteristic points. For impedance cardiography signals, characteristic points of the signal dz/dt, including its peaks, start-point and end-point of ventricular ejection are detected and located by using singularities of wavelet transform (e.g., crossover points, maxima, minima). Experiment results showed validity of the approach. PMID- 17282805 TI - Detection of arousals in patients with respiratory sleep disorders using a single channel EEG. AB - Frequent arousals during sleep degrade the quality of sleep and result in sleep fragmentation. Visual inspection of physiological signals to detect the arousal events is inconvenient and time-consuming work. The purpose of this study was to develop an automatic algorithm to detect the arousal events. We proposed the automatic method to detect arousals based on time-frequency analysis and the support vector machine (SVM) classifier using a single channel sleep electroencephalogram (EEG). The performance of our method has been assessed using polysomnographic (PSG) recordings of nine patients with sleep apnea, snoring and excessive daytime sleepiness (EDS). By the proposed method, we could obtain sensitivity of 87.92% and specificity of 95.56% for the training sets, and sensitivity of 75.26% and specificity of 93.08% for the testing sets, respectively. We have shown that proposed method was effective for detecting the arousal events. PMID- 17282807 TI - Effect of Preprocessing for Result of Independent component analysis. AB - In recent years, scientists, doctors in the field of biomedical engineering and researchers of the correlated fields have been concentrating on study of activities of bioelectricity of different cortex fields of human brain on the condition of different evocable and cognitive stimulations, and try to test human psychology and physiology, and control exterior environment. Independent component analysis is a tool that can help people to distinguish and understand various EEG signals. To the signal that we know very little, we can get very good explanation by using independent component analysis. In this paper a new algorithm is introduced that is adapted to the preprocessing of data that is dealt with by independent component analysis. This algorithm can not only accelerates the decomposing speed of independent component, but also can get the higher amplitude of extraction of steady-state visual evoked potentials. PMID- 17282806 TI - Heart sounds separation from lung sounds using independent component analysis. AB - Heart beat is an unavoidable source of interference during lung sound recording. This disturbance is more significant at low and medium breathing flow rates. Removing heart sounds (HS) from lung sound recordings or vice versa is a challenging task but of great interest for respiratory specialists and cardiologists. In this study, to separate the two signals, a novel HS separation method based on Independent Component Analysis (ICA) is developed. This method applies an ICA algorithm to the spectrograms of two simultaneous lung sound recordings obtained at two different locations on the chest and yields the independent spectrograms of the separated signals. Then, by implementing the Inverse Short Time Fourier Transform (ISTFT), the separated signals are reconstructed in the time domain. The method was applied to data of two healthy subjects. Analysis of the results as well as subjective inspections indicate the efficiency of the proposed method in terms of HS separation from lung sounds. PMID- 17282809 TI - Coherence Characteristics of Gamma-band EEG during rest and cognitive task in MCI and AD. AB - The aim of this study is to investigate whether EEG coherence during different functional states facilitates the detection of AD-related EEG changes; and which brain regions these changes were. The EEGs in both rest and performing the cognitive task states of 3 groups was recorded for coherence measure. The 3 groups are the mild cognitive impairment (MCI) group, Alzheimer's disease(AD) and the healthy control group. In rest state, coherence value of EEG for AD group was lower than that in other two groups in channel pairs of Fp2-T4, F4-C4 (P<0.01) and F3-C3, Fp1-T3, P3-O1 (P<0.05). There was no significant difference between the MCI and control. In cognitive performing state (counting the target number), coherence of EEGs in all channel connections for AD group were lower compared with MCI and control group. Furthermore, in Fp2-T4 (prefrontal-temporal) and F4 C4(frontal-central) pairs, MCI showed significant lower coherence than that in control. The conclusion of this study was that the coherence of EEG would seem to be a useful and more sensitive indicator for cognitive impairment in cognitive performing state than that in rest, and AD patient showed coherence abnormal changes in more regions in this state. The abnormal localization also suggested the AD-related cognitive impairment maybe commence with frontal activity abnormality and then spread to the other brain regions. PMID- 17282808 TI - Pulse photopletismography amplitude decrease detector for sleep apnea evaluation in children. AB - A method for automatic detection of sleep apnea using pulse photopletismography signal (PPG) is proposed. This method is based on a detection of decreases on PPG amplitude fluctuations. The proposed detector is composed of three stages: pre processing, envelope detection, based on root mean square series or Hilbert transform, and decision algorithm based on an adaptive threshold. The detector has been evaluated using simulated and real signals. Sensibility and positive predictive value of the detector where 76% and 73% for real signals. A clinical study to sleep apnea diagnosis in children based on this detector has been carried out. PPG attenuation events per hour ratio Eh has statistical significance (p < 0.05) to classify children as normal 13.5 ± 6.35 Eh(mean ± SD) or pathologic 21.1 ± 8.93 Eh. PMID- 17282810 TI - Spectral subtraction and cepstral distance for enhancing EEG entropy. AB - Electroencephalographic (EEG) signals are normally acquired in the presence of background noise which causes inaccurate or false entropy measurement throughout the signal. In this paper, spectral subtraction is used to pre-process EEG signals to improve the accuracy of computing the subband wavelet entropy (SWE). The silent period in the EEG signal is identified via cepstral distance which allows its entropy to be set to zero. The EEG signal presented in this paper represents various stages of brain recovery obtained from a rodent following global cerebral ischemia. The various subband entropies are calculated using wavelet decomposition in EEG subbands, namely Delta, Theta, Alpha, Beta and Gamma. The utilization of spectral subtraction improved the accuracy of the SWE as compared to energy thresholding. PMID- 17282811 TI - Supervised and Unsupervised Learning Systems as a Part of Hybrid Structures Applied in EGG Signals Classifiers. AB - This paper aims at investigating an unsupervised learnt neural networks in classifier applications and comparing them to supervised perceptron type nets. The proposed solutions focus on combing the time-frequency preliminary analysis by means of wavelet transform with application of self organizing maps. Using wavelet transform as a feature extraction tool allowed to reveal important parameters included both in time and frequency domain of non-stationary electrogastrographic signals, which were classified in elaborated systems. Proposed structures were tested using the set of clinically characterized EGG signals of 62 patients, as cases with different level rhythm disturbances from bradygastria up to tachygastria together with some artifacts of non-stationary character such as muscle thrill etc. Additionally similar control group of healthy patients was analyzed. The results of the proposed methodology are illustrated in the measure of sensitivity and specificity, where the best classifier based on Kohonen maps with preliminary wavelet processing reached the performance above 90%. PMID- 17282812 TI - Detection Of QRS-Wave In Electrocardiogram: Based On Kalman And Wavelets. AB - An algorithm using wavelets and Kalman filtering method has been developed for QRS detection. The algorithm takes following steps: i) We use a RLS adaptive algorithm to establish a model of the electrocardiogram. Thus the algorithm can change its own model according to the change of the electrocardiogram. ii) Based on the model established in stage i), we combined the wavelet and Kalman Algorithm, decomposed the signal to several scales, filtering the signal in each scale. And then, iii)A decision rule is used to determine the QRS complex. The method was tested on ECG data form the MIT database, and experimental results show that the method is effective, and the influence of the noise can be eliminated. PMID- 17282813 TI - Center of pressure (COP) during the Postural Balance Control of High-Heeled Woman. AB - This study addressed the effect of balance control problems of the high-heeled women. Clinical relationships have been proposed linking foot ailments or pain to wearing high heels, yet little quantitative research has been done on the relationship between bare foot and high feeled foot. The purposes of this study were to objectively quantify the displacements and velocities of center-of- pressure (COP) of body during two-way waist pulling and to compare the differences between barefooted and high-heeled situations. We used a waist pulling system which has three different magnitudes to sway the subjects. We found that the kinematic information of barefooted and high-heeled women's COP is very important in understanding the mechanism of postural balance control of women in every-day life. In the high-heeled's case, the displacement of COP increases in 200% as against bare footed. Also the velocity variation of COP grows two times than the bare footed. PMID- 17282814 TI - Discovering EEG Signals Response to Musical Signal Stimuli by Time-frequency analysis and Independent Component Analysis. AB - In recent years, a lot of research has focus on the physiological effect of music. The electroencephalographic (EEG) is often used to verify the influence of music on human brain activity. In this study, we used frequency distribution analysis and the independent component analysis (ICA) to analyze to discover the EEG responses of subjects with different musical signal stimuli. It is expected that some features on EEG can be demonstrated to reflect the different musical signal stimuli. The EEG of six healthy volunteers listening different music was recorded. We used International 10-20 System to get 19 channels of EEG signal. Musical signal stimuli are metal music, sonata music and the favorite music selected by subjects. Spectra analyses based on Fourier transform were applied to obtain the α,β,γ and θ band power of EEG signal under different music stimuli. We used the power at each band of each channel as the features of EEG. The correlation of the features between different situations and subjects was used to show which channel display the difference of EEG signals. Besides, ICA was applied to assist us in the process of isolating noise components and to provide cues to explain the functions of different brain areas in point of neurology. The result showed that some independent components obtained from ICA can demonstrate more significant difference for different music. The features composed of spectral power of each band are very similar in listening metal music, but showed less similarity in listening sonata music. PMID- 17282815 TI - Optimal discrete wavelet design for cardiac signal processing. AB - The question of designing the best wavelet for a given signal is discussed from the perspective of orthogonal filter banks. Two performance criteria are proposed to measure the quality of a wavelet, based on the principle of maximization of variance. The method is illustrated and evaluated by means of a worked example from biomedicine in the area of cardiac signal processing. The experimental results show the potential of the approach. PMID- 17282816 TI - Multiresolution analysis of transient evoked otoacoustic emission. AB - To improve transient evoked otoacoustic emission (TEOAE) test accuracy, a new technique in presented based on multiresolution signal decomposition. Using a wavelet function which optimized according to an active cochlear model, time frequency distribution of TEOAE is obtained. The coefficients of the filter bank are determined from Morlet mother wavelet function in the analysis section. In the synthesis section, time windows are obtained from deduced latency curve. By applying this multiresolution analysis, the correlative noise would be canceled. Therefore, the wave reproducibility can be increased without loss of measuring reliability. In abnormal cases where response is not expected the correlative noise is considered as response are completely disappeared. Thus this will increase the accuracy of screening results. PMID- 17282817 TI - A guideline for Parameter Design of Body Surface Laplacian Electrodes and its Application in EGG Detection. AB - The influence of dimension parameters on the performance of Body-surface Laplacian electrodes is studied in this paper. Some rules about the parameter optimization design are presented. The investigation suggests that the effective radius b should be equal to the inner radius of the ring electrode in order to reduce the relative error. Besides, in the presence of weak bioelectrical signals, reasonably increasing b would be helpful to improve SNR. Furthermore, an evaluation method based on these principles is prompted, as an instance of which, feasibility of introducing Surface Laplacian technique into EGG exploration is discussed. PMID- 17282818 TI - Application of wavelet analysis to the plethysmogram for the evaluation of mental stress. AB - The present study proposes a new stress evaluation technique using the photoplethysmogram (PTG). Heart rate variability (HRV) is often used to evaluate mental stress. HRV can be measured from an electrocardiogram (ECG). The frequency variability of HRV and mental stress response are related. PTG also indicates changes in emotional response. PTG can easily be measured without body surface electrodes. This method is less invasive than ECG measurement. We attempt herein to evaluate mental stress by wavelet analysis of the PTG. PTG was measured in the resting and mental stress states, and wavelet transformed PTGs were compared. In nine out of ten subjects, the wavelet result for PTG revealed a decrease in the frequency band. PMID- 17282819 TI - Wavelet approach in noise enhancement of balance control. AB - To analyze the dynamic characteristics of the postural sway measurements, the curves of the velocity and acceleration of the postural sway measurements were used. METHOD: The curves of smoothed velocity and acceleration were got through the filter of Haar wavelet packet decomposing function. RESULT: At the increasing of age, the velocity and acceleration of the postural sway measurements are increasing, but they decrease when the noise are introduced. SUMMARY: For those non-stochastic signals of certain physical explanation, the context method is suitable for analyzing the status of dynamic system. PMID- 17282820 TI - Optimization of the Continuous Wavelet Transform for DSP Processor Implementation. AB - The redundant wavelet transform is an effective tool when emphasis is on the analysis of non-stationary signals and on localization and characterization of singularities. Here we describe an optimized method to implement a B-spline based redundant wavelet transform (RWT) on a Digital Signal Processor (DSP) for integer scales. Expressions are derived to give an exact operation count at any integer scale m for any B-spline of order n. Finally experimental results are given using cubic b-spline as scaling function and first-and second-order derivative of B splines as wavelets. It has been shown that optimized method improves the execution speed over the standard method by 20-28%. PMID- 17282821 TI - Non-negative matrix factorizations of spontaneous electroencephalographic signals for classification. AB - Non-negative matrix factorization (NMF) is an algorithm that is able to learn a parts-based representation. The paper proposes a new spontaneous EEG classification method for attention-related tasks. NMF was employed as feature extraction tool, which leads to more localized and sparse features than other two reference methods: power spectrum method and principal component analysis. With conventional back propagation neural network classifier, several experiments were carried out. It was showed that the NMF-ANN structure preserved the spatio temporal characteristics of EEG signals. PMID- 17282822 TI - Signature Verification Using N-tuple Learning Machine. AB - This research presents new algorithm for signature verification using N-tuple learning machine. The features are taken from handwritten signature on Digital Tablet (On-line). This research develops recognition algorithm using four features extraction, namely horizontal and vertical pen tip position(x-y position), pen tip pressure, and pen altitude angles. Verification uses N-tuple technique with Gaussian thresholding. PMID- 17282823 TI - Contact-based Simulated Annealing Protein Sequence Alignment Method. AB - Protein sequence alignments reveal the evolutionary information between homologous sequences. Traditional sequence alignment methods only use sequence information and the structure information from template is ignored. Recently, Kleinjung et al. developed a contact-based sequence alignment method that used the structural information from side-chain contacts. Alignment scores are provided by the CAO (Contact Accepted mutatiOn) substitution matrices. Kleinjung et al. devised an approximate dynamic programming algorithm for protein sequence alignment, on the assumption that the distance between the contacting residues during evolution has been conserved. However, such assumption is not suitable for insertion/deletion events during evolution. In this paper, the contact-based simulated annealing alignment method has been proposed, which can find the optimal alignment solution between two protein sequences without any restriction. The alignment score is calculated by the sequence-based scores and the weighted contact-based scores. A new parameter, the contact-penalty r, has been introduced. When the contacting residue in the template aligns with gap in the query sequence, the total alignment score is decreased by a contact-penalty. All the parameters including relative weight w of CAO scores versus Blosum62 scores, matrix constant c for CAO scores, gap-open penalty p, gap-extension penalty q and contact-penalty r are re-optimized by genetic algorithm. Testing on the Homstrad database shows that the accuracy of this method is 85.4%, which is higher than that of Kleinjung's method by about 3.6 percent. Such method can be useful in many biological problems such as protein remote homology detection, comparative modeling and fold recognition. PMID- 17282824 TI - Using motifs in the prediction of eukaryotic protein subcellular localization. AB - Subcellular location of a protein is one of the key functional characters as proteins must be localized correctly at the subcellular level to have normal biological functions. In this paper, all motifs in PROSITE were examined and those that are indicative to eukaryotic protein subcellular localizations were picked out. A corresponding motif module was built and combined to our former work: LOCSVMPSI. Prediction results of this combined method were compared to LOCSVMPSI as well as several other existing methods for subcellular localization. The combined method achieved highest overall prediction accuracy among all listed methods and improved the over-all and each-location accuracies of LOCSVMPSI by 3% 8%. Further analysis indicates the combined motif method is very effective in eukaryotic protein subcellular localization prediction. PMID- 17282825 TI - A neural network method for prediction of proteolytic cleavage sites in neuropeptide precursors. AB - Proteolytic processing occurs predominantly at basic amino acid residues. The existence of the cleavage sites not recognized by rules proposed in previous studies prompts us to test whether, and to what extent, the sites cleave. Due to the imbalanced cleavage site database from SWISS, Smote combined with Tomek links is applied to over-sample the data. A neural network method is then developed to predict the probabilities of proteolytic processing occurrences at the sites in neuropeptide precursors. The sensitivities are 91%, 93%, 91%, 90%, 79% and 83% for KR, RR, RK, KK, R and K, respectively, which is significantly better than previous prediction schemes. PMID- 17282826 TI - Alternative base calling method for resequencing microarrays. AB - Analysis of high density oligonucleotide arrays for resequencing requires methods which are highly robust and accurate. We introduce an alternative base calling method built upon ABACUS with the particular advantage of achieving a very low rate for false positive detection of heterozygotes. PMID- 17282827 TI - A Neural Network to Locate the Copper-binding sites of Metalloprotein. AB - This paper presents an application of neural networks in location of the copper binding sites of metalloprotein. Using annotated metalloprotein downloaded from PDB, sequences including copper-binding sites were extracted. By further finding the particular core segments of copper-binding sites, the input and output information for training is polished. Moreover, this paper investigates the number of input nodes whose input information was coded by the residues' hydrophobic values, the number of hidden nodes, the size of training window. Back propagation algorithms were chosen for training neural networks. Results showed that the method was capable of efficiently identifying copper-binding proteins and predicting copper-binding sites at a very high accuracy. PMID- 17282828 TI - Client side decompression technique provides faster DNA sequence data delivery. AB - DNA sequences are generally very long chains of sequentially linked nucleotides. There are four different nucleotides and combinations of these build the nucleotide information of sequence files contained in data sources. When a user searches for any sequence for an organism, a compressed sequence file can be sent from the data source to the user. The compressed file then can be decompressed at the client end resulting in reduced transmission time over the Internet. A compression algorithm that provides a moderately high compression rate with minimal decompression time is proposed in this paper. We also compare a number of different compression techniques for achieving efficient delivery methods from an intelligent genomic search agent over the Internet. PMID- 17282829 TI - The application of Linear Cryptanalysis to Medical Information Security. AB - This paper summarizes some of the key issues of medical information security and is intended to spark discussion and generate comments for improvement. First we produce four definitions and one lemma of linear cryptanalysis about medical information, and then accordingly come to four important application of linear cryptanalysis to medical information security. PMID- 17282830 TI - An ontology for the integration of multiple genetic disorder data sources. AB - As a huge amount of gene disorder information is available on the Internet, there is an increasing requirement to integrate these data sources. The integration of gene disorder data sources provides an important tool in the research of life science, therapeutics, and genetic disease prevention and inhibition. The key challenge of such integration is how to deal with semantic heterogeneity of multiple information resources. The paper proposes an ontology-based approach to describe and extract the semantics of genetic disorder terminologies and provides a mechanism for sharing and reusing genetic disorder knowledge. According to this unified meta model, heterogeneous gene disorder data sources can be integrated, and a semantic middleware has the ability to do reasoning on the knowledge base of gene disorder for users and applications' various queries. PMID- 17282831 TI - Considerations of MCNP Monte Carlo code to be used as a radiotherapy treatment planning tool. AB - The present work has simulated the photon and electron transport in a Theratron 780® (MDS Nordion)60Co radiotherapy unit, using the Monte Carlo transport code, MCNP (Monte Carlo N-Particle). This project explains mainly the different methodologies carried out to speedup calculations in order to apply this code efficiently in radiotherapy treatment planning. PMID- 17282832 TI - A genome signature based on markov modeling. AB - We propose a "genome signature" for bacterial genomes based on a triplets Markov model. Without the alignment or data preprocessing required by traditional analysis methods, the model is shown to efficiently capture identifying genomic information at genus, species and strain levels. Based on the model, a simple distance measure is proposed for constructing phylogeny trees. Unlike other genome signatures based on word frequency with problems balancing word length and window size, the method has been shown to work successfully with both bacterial whole genome data and individual eukaryotic genes. Applications of the model to phylogenetic analysis and sequence fragment identification are presented. PMID- 17282833 TI - SMA: An Efficient Tool for Large-Scale Multiple Alignment. AB - To compare large numbers of genomic sequences of related virus, such as HIV, biologists have an increasing need for a method that can efficiently handle hundreds, even thousands, of genomic sequences accurately enough to correctly align these conserved features. In this paper, we introduce a new and efficient tool named SMA that can easily accommodate large-scale virus genomic sequences. A high-throughput test on 706 HIV-1 genomic sequences shows that SMA is much faster than the available programs with at least the same performance. SMA is a good improvement of existing algorithms for high-volume multiple sequence alignment. It offers an option that provides improved speed and accuracy compared with currently available programs. SMA is freely available at http://mathbio.nankai.edu.cn/e_version/align_query.php. PMID- 17282834 TI - An approach in building a chemical compound search engine in oracle database. AB - A searching or identifying of chemical compounds is an important process in drug design and in chemistry research. An efficient search engine involves a close coupling of the search algorithm and database implementation. The database must process chemical structures, which demands the approaches to represent, store, and retrieve structures in a database system. In this paper, a general database framework for working as a chemical compound search engine in Oracle database is described. The framework is devoted to eliminate data type constrains for potential search algorithms, which is a crucial step toward building a domain specific query language on top of SQL. A search engine implementation based on the database framework is also demonstrated. The convenience of the implementation emphasizes the efficiency and simplicity of the framework. PMID- 17282835 TI - A distributed approach for a multiple sequence alignment algorithm using a parallel virtual machine. AB - Multiple sequence alignment is a central topic of extensive research in computational biology. Basically, two or more protein sequences are compared so as to evaluate their similarity. This work reports a methodology for parallel processing of a multiple sequence alignment algorithm (ClustalW) in an environment of networked computers. A detailed description of the modules that compose the distributed system is provided, giving special attention to the way a dynamic programming algorithm can be executed in parallel. Extensive experiments were done to evaluate performance and scalability of the method. Results show that the proposed method is efficient and offers a real advantage for large-scale multiple protein sequence alignment. PMID- 17282836 TI - A protein structure data and analysis system. AB - In this paper, we present the design and implementation of a protein structure data and analysis system that is only used in the lab for analyzing the proprietary data. It is capable of storing public protein data, such as the data in Protein Data Bank (PDB) [1], and life scientists' proprietary data. This toolkit is targeted at life scientists who want to maintain proprietary protein structure data (may be incomplete), to search and query publicly known protein structures and to compare their structure data with others. The comparison functions can be used to find structure differences between two proteins at atom level, especially in mutant versions of proteins. The system can also be used as a tool of choosing better protein structure template in new protein's tertiary structure prediction. The system is developed in Java and the protein data is stored in a relational database (Oracle 9i). PMID- 17282837 TI - An integrated cancer biomarker information system. AB - Rapid progress in functional genomics is yielding unparalleled opportunities for cancer biomarker discovery. Several procedures including data collection, analysis, verification, and visualization are necessary to identify cancer biomarkers from continuously updated microarray data, which are derived from multiple tissue sources using various methods. BioMarker is designed to integrate these procedures in a user-friendly manner, for practical application by cancer researcher and clinicians. From the feedback of clinical and research application, BioMarker is the first effort to provide a system that facilitates all aspects of biomarker discovery from microarray datasets. PMID- 17282838 TI - GAVis: a Tool for Visualization and Control of Genetic Algorithms for -omic Data Analysis. AB - A visualization and steering application, GAVis, has been developed to aid in understanding the behavior of and guiding the convergence of genetic algorithms running in parallel over long time periods. When classification techniques such as Support Vector Machines (SVMs) paired with complete leave-one- out validation are used as a fitness function for identification of markers in - omic data, the time to complete one generation can exceed an hour on modern high-performance computing clusters. Separate solution populations on "islands" can help maintain a more diverse solution space and conveniently map to compute nodes on a cluster. Adjustments can be made at runtime to speed the convergence of genetic algorithms by stimulating lagging island populations with migrations of high-performing individuals or by selectively increasing mutation rates. PMID- 17282839 TI - Development of a laboratory information system for cancer collaboration projects. AB - Technological advances increase the rate and quality of biomedical data collection. To exploit these advances to the fullest, laboratory information management systems (LIMS) have been developed to integrate laboratory equipment with software controls so as to achieve an automated and seamless workflow process. Ultimately, researchers and clinicians must collaborate closely to achieve a comprehensive interpretation of heterogeneous biomedical data, especially with respect to clinical diagnosis and treatment. We present eOncoLIMS, a modular data and process management system designed to provide the infrastructure and environment for a collaborative cancer research project. This system can be further extended to other collaboration projects to achieve a complete solution to research and clinical problems. PMID- 17282840 TI - Multithreaded multiple sequence alignments. AB - Based on the mixed idea of Progressive alignment and Divide-and-conquer alignment, two different multithreaded multiple sequence alignment programs, depending on how the guide tree(s) would be applied, are implemented for checking the improvements of alignment speed and sensitivity. The single-tree alignment builds a uniformed guide tree for the full-length sequences at the beginning, which will be used by all the sub-alignments as guide tree. In multiple-tree alignment, sequences will be firstly cut into pieces and these sub-sequences will build their own guide trees to guide their individual alignments. Multiple-tree alignment seems having a better speedup performance than the single tree alignment, but neither of them, at this stage, shows ideal sensitivity results as the number of threads increases. Therefore, some heuristic methods for fixing the cut points were suggested for future improvement, such as overlapping alignment and sliding window alignment. PMID- 17282841 TI - Discussions on "Biomedical Signal Processing": Content, teaching and training. AB - In this paper, discussed are points cumulated in our practices in taking the course of "Biomedical Signal Processing". The contents include the arrangement of the contents, selection of multi-teaching methods, reformation of examination methods, the way of communication with students and the design of experiments. PMID- 17282842 TI - Aligning the clinical engineering education program with the career requirements. PMID- 17282843 TI - The application of visual reality in medicine. AB - The technique of visual reality has got a rapid development in medicine field, especially in medical education field. With its advantage of intuition and flexibility, VR has gained agreement widely. In this paper, the concept, category, application will be introduced. Author also gives some suggestion to improve the applications of VR technique in medicine field. PMID- 17282844 TI - Research of Knowledge-sharing Mechanism Oriented to Hospital Management. AB - This paper, aiming at the characteristics of hospital management in terms of knowledge management, firstly analyzes the importance of knowledge sharing and the obstacles which exist. In theory it provides knowledge sharing mechanism model and make a construction in culture, organization, motivation mechanism and technology, etc.. The paper perfects the research of knowledge management in hospital management and offers beneficial references for the improvement of service quality and efficiency. PMID- 17282845 TI - A Web-based Examination System Based on PHP+MySQL. AB - The design and implementation of web-based examination system constructed by PHP and MySQL is presented in this paper. Three primary parts, including students',teachers' and administrators', are introduced and analyzed in detail. Initial application has demonstrated the system's feasibility and reasonability.* PMID- 17282846 TI - Construction of Multimedia Courseware and Web-based E-Learning Courses of "Biomedical Materials". AB - In order to reform the traditional teaching methodology and to improve the teaching effect, we developed new teaching system for course "Biomedical Materials" in our university by the support of the computer technique and Internet. The new teaching system includes the construction of the multimedia courseware and web-based e-learning courses. More than 2000 PowerPoint slides have been designed and optimized and flash movies for several capitals are included. On the basis of this multimedia courseware, a web-based educational environment has been established further, which includes course contents, introduction of the teacher, courseware download, study forum, sitemap of the web, and relative link. The multimedia courseware has been introduced in the class teaching for "Biomedical Materials" for 6 years and a good teaching effect has been obtained. The web-based e-learning courses have been constructed for two years and proved that they are helpful for the students by their preparing and reviewing the teaching contents before and after the class teaching. PMID- 17282847 TI - An E-learning Content Authoring tool for Transforming DICOM into SCORM. AB - Today e-learning is not impossible, and it becomes a generation of next education technology. Now e-learning has two directions of developing: the one is the construction of Learning Management System (LMS); and the other is the developing reusable content. Our studies focus on the developing content. Now the medical image information system of hospital usually is Picture Archiving and Communication System (PACS). In PACS, the form of information and image are HL7 and DICOM; for the reusability of content, we decide SCORM to be our conformant. However, the forms of data have difference between SCORM, and DICOM, so in our studies, we will design an authoring tool that can transform the information from DICOM image into the SCORM course. PMID- 17282848 TI - An Improved Integrated Electronic Nose for Online Measurement of VOCs in Indoor Air. AB - An improved integrated electronic nose mimic human olfactory system was developed and applied to online measurement of volatile organic compounds (VOCs) in indoor air. An enrichment unit based on active adsorbent sampling and thermal desorption was employed to lower detection limits to matching environmental concentrations. Tow kinds of optimized arrays of sensors were designed, and an FFT and RBF artificial neural network were employed for dynamic signal extraction and pattern recognition, respectively. Results showed good performance of our electronic nose in qualitative and semi-quantitative measurement. PMID- 17282849 TI - IGES Interface for Medical 3-D Volume Data. AB - Although there are many medical image processing and virtual surgery systems that provide rather consummate 3D-visualization and data manipulation techniques, few of them can export the volume data for engineering analyze. The thesis presents an interface implementing IGES (initial graphics exchange specification). Volume data such as bones, skins and other tissues can be exported as IGES files to be directly used for engineering analysis. PMID- 17282850 TI - Interaction techniques for the exploration of hepatic vessel structure. AB - Hepatic vessel system is one of the most complex vessel systems in human body. For liver surgical planning, morphology and topology analysis of the hepatic vessel system is of our major interest. In this article, we present a new method to analyze the liver vessel system. Starting from the raw CT data set, vessel system is segmented. Based on that, then skeleton line of the vessel system is extracted and a symbolic vessel tree is constructed. The interactive analysis is achieved by combination of the abstract vessel tree information and the vessel surface model. The experimental results illustrate that the algorithm is effective, easy to implement, and addresses fully interaction facilities. The whole processing involves no human interventions, except the preprocessing of CT images. PMID- 17282852 TI - Study of influencing factors on Electrical Impedance Scanning Imaging. AB - Electrical impedance scanning (EIS) is a new adjunctive diagnostic method for women breast cancer examination. In clinic research, we found some influencing factors which can induce a bad EIS imaging results. In order to analyze the influencing factors on EIS imaging and find the solutions, we set up an EIS workbench which can simulate the influencing factors that may happen in a clinic. We studied the influencing factors from size, depth of the target; the influence from the poor contact; the influence from the unparallel current field. The experiment results show that the detectability of EIS system is a function of the depth, the size and the area of electrodes; a good contact between the probe and the skin can decrease the artificial imaging; using the imaging algorithm can calibrate the imaging induced by unparallel current field. PMID- 17282851 TI - Research on virtual chinese human eye and its application. AB - In this paper a method to establish Virtual Chinese Human Eye was presented. In this method, five datasets were established base on eye tissue slices. 3-D structure model, physical model, and physiological model of eyeball were built up. Someone of them can be used in education and clinic. The research on Virtual Chinese Human Eye still awaits long-term and will have a major effect. PMID- 17282853 TI - Arnoldi preconditioning for solving large linear biomedical systems. AB - Simulations of biomedical systems often involve solving large, sparse, linear systems of the form Ax = b. In initial value problems, this system is solved at every time step, so a quick solution is essential for tractability. Iterative solvers, especially preconditioned conjugate gradient, are attractive since memory demands are minimized compared to direct methods, albeit at a cost of solution speed. A proper preconditioner can drastically reduce computation and remains an area of active research. In this paper, we propose a novel preconditioner based on system order reduction using the Arnoldi method. Systems of orders up to a million, generated from a finite element method formulation of the elliptic portion of the bidomain equations, are solved with the new preconditioner and performance is compared with that of other preconditioners. Results indicate that the new method converges considerably faster, often within a single iteration. It also uses less memory than an incomplete LU decomposition (ILU). For solving a system repeatedly, the Arnoldi transformation must be continually recomputed, unlike ILU, but this can be done quickly. In conclusion, for solving a system once, the Arnoldi preconditioner offers a greatly reduced solution time, and for repeated solves, will still be faster than an ILU preconditioner. PMID- 17282854 TI - The Establishment of the Mathematical Model of the 2ndDegree Burn Injury of Human Tissues and Its Application. AB - A quantitative analysis of the 2nddegree burn injury of human tissues and the relevant mathematical model are presented in this paper. Unlike the general criterion extensively adopted by doctors that pay much attention to the degrees of the skin burn damage such as the area, depth and color of the damaged skins, the paper emphasizes the cause-and-effect of the 2nddegree burn injury of the human tissues. Based on the theoretical study and the experimental observations, the paper presents a quantitative analysis method to establish a relationship between the 2nd degree burn and the physiological parameters of the human body as well as the physical parameters of the exposing surroundings. The comparisons of the theoretical study with the experimental data have been made and the results are quite satisfactory. The application of the mathematical model in the test of thermal protective performance of fire protection clothing is also presented. PMID- 17282855 TI - Systematic reduction of a bursting neuron model. AB - We present our research in reducing the complexity of a conductance-based neural model. We utilize previously published techniques, as well as novel methods, to reduce a 14 state variable, conductance-based model of a bursting neuron to a 4 state variable hybrid integrate-and-fire model. The reduced model exhibits activity that is quantitatively similar to the complex model both in single-cell bursting mode, and when coupled to another neuron. PMID- 17282856 TI - Facilitation of perceptual filling-in for spatio-temporal frequency of dynamic textures. AB - Objects are perceived to fade and disappear within a few seconds under certain conditions when a small object surrounded by a moving texture is presented in human peripheral vision. This phenomenon is called perceptual filling-in or fading. Investigation of filling-in properties is important to understand visual information capture and processing. Previous studies have adopted filling-in time to evaluate the facilitation of filling-in. From this viewpoint, we propose a model of the filling-in process to address the phenomenon by which a small homogeneous area (filling-in target), which is surrounded by spatio-temporal frequency limited random-dot dynamic textures, is presented to an observer's peripheral vision (Proc.IC-EMBS2003). The model expresses target distinguishability from the surrounding texture. This study measured time to filling-in for various spatio-temporal frequencies of target-surrounding dynamic textures. Spatio-temporal frequency sensitivity of human vision was also estimated. Applying these results to the proposed model, it was suggested that M channel pathway of LGN facilitates perceptual filling-in. In contrast, the P channel pathway is assumed not to facilitate, but rather inhibit, filling-in. PMID- 17282857 TI - Study of Feature Classification Methods in BCI Based on Neural Networks. AB - Feature classification is one of the important aspects in Brain-computer interfaces (BCI) system. It has been known that a higher precision can be achieved if use neutral networks in a proper way for feature classification. In this paper, three feature identification ways were introduced and discussed. In the experiment of left-right hand classification, the arithmetic of the small mean square difference is proposed and studied, so as to get a good converging in the task classification. The design method of input and output layer for the BP neural network was discussed. Experiment results show that it is a feasible processing algorithm to classify the different events. PMID- 17282858 TI - Representing multidimensional medical image in compact format. AB - In this paper, we propose a novel approach for effectively expressing multidimensional medical image data in spatial database systems with a compact form, which uses the vector compressed from position vector [5]. Here Hyperplane are used to express the position and forms of a various dimensions spatial object. A set of hyperplanes splits a space into convex polytopes, each having a position vector [+...-0-...--], which is a sequence of positions with the set of hyperplanes. Position vectors can be used to evaluate the spatial database operations, intersection, union and difference between two or more objects in any dimension. For easy compression, we firstly propose the cell position vector (CPV) representation of a position vector. The CPV compression algorithm is based on following ideas: only the position numbers of ;0' s in a position vector of zero-dimensional cell, and the position numbers of ;+'s, ;0's, ;-'s in a position vector of a top-cell are saved. We introduce a modified run length algorithm to compress CPVs of top-cells. Experimental evidence shows that our model has only 5% data size of position vector model for a three dimensional heart test data. We also have implemented this storage method on an object database system based on a compact form of CPV. PMID- 17282859 TI - Physiological factors of the small intestine in design of active capsule endoscopy. AB - Wireless capsule endoscope is a device used to examine the diseases in the small intestine. At present, the capsule endoscope moves through the gastrointestinal tract by natural propulsion of peristalsis. In order to achieve real-time diagnosis and treatment-related procedure, the capsule endoscope is required to be self-actuated and controlled. Different from soild environment, the small intestine is an extremely flexible tube. The unique structure and tissue cause many challenges for the capsule actuation. In this paper, the features, motility, and frictional force of the small intestine are analyzed for determining the design strategy. In-vitro experiment results show the power of magnetic force needed for driving the capsule and the factors that affect the magnitude of the driving force as well. Based on the analysis of the small intestime, a scheme of magnetically-actuated active endoscopy is proposed in the end. PMID- 17282860 TI - Primary analysis of the first ray using a 3-dimension finite element foot model. AB - A three-dimensional accurate foot model including bones, cartilages, ligaments and tendons was developed from 3D reconstruction of CT images. The model was used to analyze stress-strain of the joint between the first metatarsal and the medial cuneiform and to study the relationship of the range of motion of the first ray and hallux valgus. PMID- 17282861 TI - Pulse and energy pulse height tally comparison in breast dosimetry with Monte Carlo radiation transport codes: MCNP5 and PENEASY(2005). AB - The authors present a review of tallying processes with non-Boltzmann tallies under Monte Carlo simulations. A comparison between different pulse and energy pulse height tallies has been done with MCNP5 code and PENEASY, a user-friendly version of PENELOPE code. Several simulations have been done for estimating the pulse and energy deposited spectra in a polymethyl-methacrilate (PMMA) phantom used during quality control testing in digital mammography. In the case of MCNP5, the arbitrary energy-loss which is activated by default for particles just crossing the detector has been removed for comparing the efficiency of the tally. PENEASY works similarly, counting all scores which have or have not deposited energy in the phantom. A correction has been done to the code to remove this scoring. As derived from the results, the deposited energy has been estimated as 3.73369e-3 MeV/particle for MCNP5 and 3.25468e-3 MeV/particle for PENASY. Further studies are necessary to obtain more accurate results modeling the compression plate and the imaging system. Pulse and energy pulse height spectra are still tallies under development and all effort must be done to understand the tallying process under different applications. PMID- 17282862 TI - Organ motion prediction for medical treatments. AB - In extracorporeal shock wave lithotripsy (ESWL) and radiotherapy, real time tracking of the position of renal stones or tumors is of great importance. When the treatment system incorporates many delay factors, the treated position and the expected position may significantly differ. In this study, linear prediction is used to examine if future values from real-time tracking trajectories can be predicted accurately. The results presented here shows that predicted values can be used for the treatment targeting compensating for the systems delays. The use of up to the third future predicted value introduces less than 5% average error from the actual future positions. PMID- 17282863 TI - Evaluation of respiratory system models based on parameter estimates from impulse oscillometry data. AB - Impulse oscillometry offers advantages over spirometry because it requires minimal patient cooperation, it yields pulmonary function data in a form that is readily amenable to engineering analysis. In particular, the data can be used to obtain parameter estimates for electric circuit-based models of the respiratory system, which in turn may assist the detection and diagnosis of various diseases/pathologies. Of the six models analyzed during this study, Mead's model seems to provide the most robust and accurate parameter estimates for our data set of 5 subjects with airflow obstruction including asthma and chronic obstructive pulmonary disease and another 5 normal subjects with no identifiable respiratory disease. Such a diagnostic approach, relying on estimated parameter values from a respiratory system model estimate and the degree of their deviation from the normal range, may require additional measures to ensure proper identification of diseases/pathologies but the preliminary results are promising. PMID- 17282864 TI - Determining the influence of population variation on compliance with radiofrequency exposure limits: proposed study. AB - Currently, compliance with safety limits for human exposure to radiofrequency (RF) fields is demonstrated by methods that rely on certain assumptions and approximations, which include among other things, human anatomical features, tissue types and the dielectric properties of these tissues. This paper reviews some of the available data and outlines a proposal for an encompassing study to investigate which of these assumptions are appropriate; what approximation can be used in physical and computational modeling of humans for specific energy absorption rate (SAR) calculations (a key compliance metric); and what trade-offs can be made between accuracy and modeling requirements for practical considerations. Key issues to be investigated are how SAR varies between children and adults, between males and females, and how to model SAR in the fetus of pregnant females. It is hoped that the proposed study will produce models and methods which allow for faster, more accurate and more efficient compliance with radiofrequency exposure limits. PMID- 17282865 TI - Probabilistic control of gene networks. AB - In this paper, an approach based on Markov chains for controlling gene networks is proposed. The state of the network is represented as a probability distribution, while state transitions are considered to be probabilistic. An algorithm is proposed to determine a sequence of control actions that drives the state of a given network to within a desired state set with a prescribed minimum or maximum probability. A heuristic is proposed and shown to improve the efficiency of the proposed algorithm for a class of gene networks. PMID- 17282866 TI - Simulation Study and Function Analysis of Micro-axial Blood Pumps. AB - During past decades, various micro-axial blood pumps were invented and have gained widespread acceptance as prospective devices as circulatory support of failing hearts. Studies concerned with the effects of the pumps can be divided into two categories: in vivo studies and simulation studies using mathematical model of the pumps and circulatory system. A new mathematical model of the micro axial blood pumps is established, which can be applied to various microaxial blood pumps. By inserting the pump model into the model of canine circulatory system according to clinic setting, the pump's effects can be investigated. In this paper, simulation studies of two types of micro-axial blood pumps, Hemopump and dynamic aortic valve (DAV), are made and the results verified that blood pumps decrease the workload of the heart by increasing pump flux, stroke volume, aortic pressure and decreasing left ventricular pressure and volume, left atrial pressure, the blood pumped by the left ventricle. With the increasing of rotation speed, the benefit effects are enhanced, however, too high rotation speed may cause left ventricular collapse. For Hemopump at above 24500 rpm left ventricular collapse is observed and for DAV it is not obtained below 9000 rpm. The simulation results are found in good agreement with the in vivo experimental results. PMID- 17282867 TI - The simulation of intracranial pressure dynamics. AB - Intracranial pressure (ICP) research has significant importance in clinic. There are many internal or external factors which cause the vibration of ICP, including heart beat, breath, neural regulation, and so on. A lumped parameter mathematical model of ICP dynamics is established based on animal (dogs) experiments, which includes cerebrovascular bed, cerebrospinal fluid (CSF) formation and absorption, brain compliance, lumbar cerebrospinal fluid, and interactions between these factors. An exponential volume-pressure relationship is employed in this simulation to describe cerebrovascular compliance. The model well simulates intracranial pressure dynamics and the vibration of ICP when compared to animal experiments; the changes of parameters in simulation are consistent with animal experiments. It offers certain values for clinical ICP ward and diagnosis. PMID- 17282868 TI - The effect of glycosaminoglycans and hydration on the viscoelastic properties of aortic valve cusps. AB - This paper reviews the rationale for developing a tissue-engineered aortic valve by building up the complex microstructure from its basic components, and presents recent progress towards that goal. Over the past 4 years, we have been working on engineering the functional components of the composite valve the collagen fiber bundles, the elastin sheets, and the hyaluronan matrix that keeps the tissue hydrated. Most recently, we have been working on optimizing the geometry and material properties of the collagen constructs, by varying their size and aspect ratio, and the types of loading protocols the constructs experience during the culture process. PMID- 17282869 TI - Robust modelling of biological neuroregulators. PMID- 17282870 TI - Artificial neural networks as a tool of modeling of training loads. AB - This paper shows that extremely important element of forming speed capabilities is proper (quantitative) structure of exercise loads. This means that training means should be chosen from point of view of energy production in metabolic processes, which depends on the structure of training means from the information area and energy area, therefore on the character of work made, its intensity, duration of exercise, number of repetitions and duration of rest periods. From the training process effectiveness point of view, it is extremely important to find the correct tool for choosing means in given training cycle. The investigation results confirm the experiences of coaches and theorists of sport, that the structure of volume and intensity of exercise loads should be individually chosen with consideration of predispositions of separate athletes. Individualization of training is condition for its optimization. PMID- 17282871 TI - A dynamic three dimensional tibio femoral modeling. AB - The work presented in this paper is related to the development of a rehabilitation systems which is based on realistic and adaptive knee model. The aim of this system is to improve the comprehension of the knee movement and the diagnosis of its pathologies. In this way, we propose to express in a simple and accessible manner a three dimensional dynamic tibio-femoral model to respect the control and the measurement needs of the developed system. PMID- 17282872 TI - A novel simulation model for the motor unit innervation process. AB - A simulation model for the Motor Unit Innervation Process (MUIP) is proposed. The model is based on the Hodgkin-Huxley (HH) model, which enables it to simulate the complex dynamics of MUIPs, such as the interactions between motor unit common drive and MUIP correlation (motor unit synchrony). Some simulation results are presented and possible extensions of the model are discussed. PMID- 17282873 TI - The influence of electromagnetic field irradiated by high-voltage transmission lines on properties of cells. AB - The influence of low-frequency electromagnetic field irradiating by high-voltage transmission lines on signal transduction of cell in spleen cells of the rates have been studied by molecular-biology techniques. The spleen cells are extracted from skilled rates, which are exposed in the electromagnetic field of high voltage transmission lines with 4000 V/m and 0.09-0.1 G about 400 days. The quantity or level of phosphorylation of signal transducer and activator of transcription (STAT3) in JAK-STAT signal transduction pathway of spleen cells, which are stimulated and unstimulated by IL-2, respectively, are detected by the immunoblotting and immunobiochemistry. The results show that the expression of phospho-STAT3 in spleen cell stimulated by IL-2 differ not from that in the unstimulated cell. The former is significantly large than the latter. This shows that signal transduction of cell is affected by this electromagnetic field. The spectra of infrared absorption for the general G-proteins participating this signal transduction of cell for the controlled and exposed groups, which are measured by Nicoletic FT-IR 670 spectrometer, are obviously different both the intensity and frequency of these peaks. This shows that molecular structure or conformation of the proteins changes under influence of the electromagnetic field of high-voltage transmission lines, which results just to above changes of the JAK-STAT signal transduction of cell. PMID- 17282874 TI - Measurement of bioelectric currents based on the coupling of electric and magnetic field. AB - A method based on magneto-acoustic technique is developed to measure bioelectric currents non-invasively. Theoretically, vibrations of particles in the medium are produced due to the Lorentz force when oscillatory currents flow through medium in a steady magnetic field. These vibrations contain information of the bioelectric currents and can be detected by surface contact detector. An experimental setup is presented to detect the microampere level currents in saline and tissue. The results show the linear relationship between the acoustic signal and the current. PMID- 17282875 TI - Study of multi-freedom myoelectric prostheses with tactile sense. AB - This paper designs a bionic artificial hand that has a tactile sensing, two degrees of freedom, driven by surface electro-myography (SEMG). The tactile sensor applying PVDF as a sensitive material, fitted the finger of artificial hand, has a good dynamic response. The tactile sense is spread to the user by an electric shock generator. Using improved power spectrum ratio and data fusion method based on statistical decision-making of Bayes, the movements of hand are recognized from SEMG. The experiment proves that it is a good way that the hand is controlled by SEMG combining with tactile sensor. PMID- 17282876 TI - An understanding for the abnormal spikes of the EEG simulation in a 2-d neural network. AB - The work here presents an abnormal EEG simulation and an analysis for the abnormal spikes in the simulation by using the wavelet method. The simulation is derived from the electrophysiological model of an excitable neuron being in a disorder process. The spike wave and the multi-spike wave of the EEG morphology are reconstructed by step changes in the concentration of the intracellular calcium ions ([Ca]i). In the further work, when the concentration of [Ca] i is sufficiently large, the multi-spike wave can also be reconstructed and the spikes of the potentials are analyzed by the multi-layer wavelet method. The work will be helpful to understand how the EEG morphology is formed from the microcosmic viewpoint. PMID- 17282877 TI - Electrophysiological modeling study of ECG T-wave alternation caused by ultrahigh static magnetic fields. AB - The goal of our research is try to explain the electrophysiological mechanisms of alternation in T-wave of ECG in ultrahigh static magnetic field (SMF). The magneto-hydrodynamics model study shows that ultrahigh SMF can induce reduction in the volume flow rate of the blood in human arota more than 10%, thus may lead to anoxia condition of acute ischemia. Using an ionic-based theoretical model of the cardiac ventricular cell, we simulate transmural heterogeneous suppression of the action potential plateau and action potential duration shortening in case of different anoxia degree. The results demonstrated that anoxia may produce a significant increase in the T-wave amplitude, which may be another mechanism for the influence of ultrahigh SMF to T-wave. This finding is consistent with experimental observation. This study suggests that one should strengthen the safety inspection of ECG in MRI scan and in other application of ultrahigh SMF. PMID- 17282878 TI - Gradient weighted smoothing for MRI intensity correction. AB - In magnetic resonance imaging (MRI), surface coils have the advantage of higher signal to noise ratio (SNR) but suffer from image inhomogeneity due to the non uniform sensitivity profile. To remove bright spots caused by non-uniform sensitivity profiles, a gradient weighted smoothing method is discussed in this work. A partial differential equations (PDE) based model is applied for this locally adaptive smoothing. The filtered gradient of the corrupted image is used as the weight for smoothing. For accuracy evaluation, the energy of the histogram spectrum difference and the correlation of the intensity corrected image with the image acquired using the body coil are used as quantitative criteria. Clinical data collected on various MRI systems are used for evaluation of stability. The experimental results show that the proposed method is accurate and robust for intensity correction, and outperforms non-adaptive methods. PMID- 17282879 TI - A rapid iris location method based on the structure of human eyes. AB - Iris location is an important part of iris recognition. Speed of location and robustness of arithmetic of location are factors which we must pay attention to especially. In this paper we analyse eye images that we have based on structure characteristics of eyes, we put forward a rapid iris location arithmetic. Firstly, we get an approximative center by gray projection, we get two points that locate at left and right boundary by threshold value respectively, and we get a point that locates at the lower boundary by direction edge detection operators, then we can ensure the boundary of pupil and probable center. Secondly, we get exact pupil boundary and center by Hough transform that is processed at a small scope surrounding the probable center. Thirdly, we search two points that locate at left and right boundaries between iris and sclera along horizontal direction by using the exact center and direction edge detection operators. Then we ensure the horizontal coordinate of the center of iris based on the above two point accurately. Finally, we search two points that locate at upper and lower boundaries between iris and sclera beginning at the horizontal coordinate of the center of iris along the directions that making plus and minus thirty angles between horizontal direction respectively by using direction edge detection operators, so we ensure the coordinate of the center of iris and the boundary between iris and sclera. The experiments indicate that this method reaches about zero point two second at speed and percentage of ninety nine point forty five at precision. This method is faster than existing methods at speed. PMID- 17282880 TI - A comparative study and analysis on techniques for diffusion-weighted magnetic resonance imaging. AB - Neural scientists have long been eager to find the subcortical pathways between different parts of cortex in human brain. By far, Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) is the only noninvasive technique to achieve this task in vivo. It applies a bipolar gradient to reveal diffusion of water molecules. With the assumption that the directions of neural fibers parallel to the directions in which water molecules diffuse, we can use the DW-MRI to track the neural fibers. Various signal processing techniques have been developed in extracting the directional information via DW-MRI. In this study, four techniques that are currently being used but have not been rigorously compared for performance are evaluated via custom-designed synthetic data and phantoms. By combining different techniques in accordance with their specialties, a better approach to track finer subcortical pathways in vivo can be derived and used to verify theories in human brain mapping. PMID- 17282881 TI - Brain tissue segmentation based on corrected gray-scale analysis. AB - Image signal-to-noise ratio (SNR) and signal intensity (SI) inhomogeneities are factors that strongly affect the accuracy and precision of brain tissue segmentations in magnetic resonance image (MRI). In this work, SNR and contrast of brain images are optimized by TR and inversion recovery time TI in multi spectrum MRI data sets. SI inhomogeneities are measured in vivo using a recently developed method allowing improved correction. The three-Gaussain distribution model is used to fit histograms of the images to find the initialization parameters for an Expectation-Maximization (EM) segmentation algorithm. Compared with other methods, the field map method provides better correction of SI inhomogeneities and excellent segmentation results. PMID- 17282882 TI - Computer-Aided Diagnosis Scheme for Detection of Unruptured Intracranial Aneurysms in MR Angiography. AB - The detection of unruptured intracranial aneurysms is a major subject in magnetic resonance angiography (MRA) images. However,it is difficult for radiologists to detect small aneurysms on the maximum intensity projection (MIP) images, because adjacent vessels overlap with the aneurysm. The purpose of this study was to develop an automated computerized detection of aneurysms in order to assist radiologists' interpretation as a "second opinion." The vessels were first segmented from background by use of gray-level thresholding and region growing technique. The gradient concentrate (GC) filter was then applied to the segmented vessels for enhancement of aneurysm. The initial aneurysm candidate was identified in the GC image with a gray level threthold. For removal of false positives (FPs), we determined three features, i.e.,size,sphericity, and mean value of GC image in each of the candidate regions. Finally, the rule-based schemes with these features and quadratic discriminant analysis were applied for distinction between aneurysms and FPs. The sensitivity of our method for detection of aneurysms was 100% (7/7) with 1.85 FPs per patient. With our computerized scheme, all aneurysms were detected correctly with low FP rates, and would be useful in assisting radiologists for identifying correct aneurysms and for reducing the interpretation time. PMID- 17282883 TI - Intensity Non-uniformity Correction of Magnetic Resonance Images Using a Fuzzy Segmentation Algorithm. AB - Artifacts in magnetic resonance images can make conventional intensity-based segmentation methods very difficult, especially for the spatial intensity non uniformity induced by the radio frequency (RF) coil. The non-uniformity introduces a slow-varying shading artifact across the images. Many advanced techniques, such as nonparametric, multi-channel methods, cannot solve the problem. In this paper, the extension of an improved fuzzy segmentation method, based on the traditional fuzzy c-means (FCM) algorithm and neighborhood attraction, is proposed to correct the intensity non-uniformity. Experimental results on both synthetic non-MR and MR images are given demonstrate the superiority of the algorithm. PMID- 17282884 TI - Thalamus segmentation from MRI images by lagrangian surface flow. AB - In this paper, we present a new thalamus segmentation method for MRI images based on a new type of deformable model-Lagrangian Surface Flow. Given a MRI image, the user can interactively initialize a seed model within region of interest. The model will then start to grow according to both boundary and region information based on the principle of variational analysis. The deformation will stop when an equilibrium state is achieved. Our experiments demonstrate that the new method is robust to image noise and inhomogeneity and will not get stuck into local minima or leak from spurious edge gaps. PMID- 17282885 TI - Combined image processing techniques for characterization of MRI cartilage of the knee. AB - A common manifestation of osteoarthritis (OA) of the knee is the morphological degeneration of articular cartilage. In vivo magnetic resonance imaging (MRI) offers the potential to visualize and analyze quantitatively morphology such as cartilage thickness and volume. The purpose of this work was the development of new image processing techniques and application of existing ones for the intra and inter-subject quantitative analysis of cartilage of the knee. The process consists of MRI acquisition, cartilage segmentation, shape-based interpolation of segmented cartilage, segmentation of bone, volume registration based on bone structures, analysis, and visualization. The process is semi-automatic, the segmentation which is based on Bezier splines and edge detection requires interaction. Different shape interpolation methods were compared. The registration is based on shape matching and can be rigid-body and elastic. The analysis comprises cartilage volume and thickness calculations. The visualization allows the depiction of cartilage thickness maps overlaid on MR images or in three dimensions (3D). The cartilage segmentation and shape-based interpolation techniques were validated visually and based on the volumetric measurements of images of porcine knees which cartilage volume were directly measured using a saline displacement method. The registration technique was validated visually and using manual landmark registration. PMID- 17282886 TI - Segmentation guided robust multimodal image registration using local correlation. AB - This paper presents a unified variational framework for seamlessly integrating prior segmentation information into non-rigid registration procedures. Under this framework, in addition to the forces arises from the similarity measure in seeking for detailed correspondence, another set of forces generated by the prior segmentation contours can provide an extra guidance in assisting the alignment process towards a more meaningful, stable and noise-tolerant procedure. Local correlation (LC) is being used as the underlying similarity measures to handle intensity variations. We present several 2D/3D examples on synthetic and real data. PMID- 17282887 TI - A template effect study on voxel-based morphometry in statistic parametric mapping. AB - Voxel-based morphometry (VBM) is an automated method allowing identification of anatomical differences in the whole brain without the pre-specification of a region of interests. Spatial normalization is one of the major processes in VBM, which transforms all images to a standard template. A variety of templates were employed in VBM researches in the literature, including the MNI template and study-specific templates. Few studies were presented to test the effect of templates on the detection accuracy of VBM, although it is claimed in many papers that the study-specific template performs better. However, the creation of the study-specific template differs on the subjects included. In this paper, the gray matter (GM) difference of two groups (female vs male) was analyzed to evaluate the effects of templates on the VBM results. The statistic parametric mapping (SPM) package, as the standard software for VBM implementation, was used for analyses. PMID- 17282888 TI - Callosal Shapes at the Midsagittal Plane: MRI Differences of Normal Males, Normal Females, and GID. AB - We investigated differences in corpus callosum shape at the midsagittal plane using MRI for different subjects: normal males, normal females, and subjects with gender identity disorder (GID). We first represented callosal shapes with Fourier descriptors of callosal contours. Using linear support vector machines with soft margin, we next determined a hyperplane that separates normal males and females most optimally in the vector space spanned by Fourier descriptors. We then proposed a measure that has prominent sex difference: it is defined as the coordinate of a given callosal shape on the subspace orthogonal to the obtained hyperplane. Use of the measure provides discrimination of someone's sex with 74.17% accuracy. We further showed that the value of the measure for GID more strongly reflects their mental sex, i.e. gender, than their physical sex. PMID- 17282889 TI - Model-based Graph Cut Method for Segmentation of the Left Ventricle. AB - Model-based medical image analysis allows high level information to guide image segmentation. However, most model-based methods rely on evolution methods which may become trapped in local minima. Graph cuts have been proposed for image segmentation problems where the cost of the cut corresponds to an energy function which is then globally minimized. However, it has been difficult to include high level information in the formulation of the graph cut. We have developed a method for integrating model-based a priori information into the graph cut formulation. A 4D model prior of the left ventricle is calculated from an average of historically analyzed cases. This is scaled and rotated to the given case and a 2D spatial prior is calculated for each image. The spatial prior is then combined with pixel intensity data and edge information in the graph cut optimization. Both epicardial and endocardial contours can be found using variations of this procedure. We report results on 11 normal volunteers and 6 patients with heart disease, compared with the results from two experienced observers. A modified Hausdorff distance measure showed good agreement between the model-based graph cut and the expert observers. PMID- 17282891 TI - Automatic 4-D Registration in Dynamic MR Renography. AB - Dynamic contrast-enhanced 4-D MR renography has the potential for broad clinical applications, but suffers from respiratory motion that limits analysis and interpretation. Since each examination yields at least over 10 - 20 serial 3-D images of the abdomen, manual registration is prohibitively labor-intensive. Besides in-plane motion and translation, out-of-plane motion and rotation are observed in the image series. In this paper, a novel robust and automated technique for removing out-of-plane translation and rotation with sub-voxel accuracy in 4-D dynamic MR images is presented. The method was evaluated on simulated motion data derived directly from a clinical patients data. The method was also tested on 24 clinical patient kidney data sets. Registration results were compared with a mutual information method, in which differences between manually co-registered time-intensity curves and tested time-intensity curves were compared. Evaluation results showed that our method agreed well with these ground truth data. PMID- 17282890 TI - A novel liver perfusion analysis method. AB - In this paper we apply level set segmentation to aid in automating the clinical challenge of measuring the contrast agent concentration in liver perfusion time series. For this, we apply implicit contour methods to time series of two dimensional MRI images to yield accurate measurements of local image properties located relative to the shape of the liver across all images in the series. Our results show that Level Set Methods can be used to provide the necessary segmentation shape data to reliably measure local image intensities positioned relative to this shape throughout a time series, where the location and shape of the object to be tracked changes. PMID- 17282892 TI - A 2D/3D matching based on a hybrid approach: improvement to the imaging flow for AVM radiosurgery. AB - A new approach of registration in multimodal imaging has been developed. Modalities involved are Digital Subtracted Angiography (DSA, 2D) and Magnetic Resonance Angiography (MRA, 3D). Our approach is an hybrid one, mixing feature and intensity based approaches. This approach is based on the extraction of a anatomical referential common to both MRA and DSA. The results obtained prove the methods efficiency in a clinical context. This paper present the validation methodology to make it possible the replacement of the localization DSA examination by the diagnosis one, thus avoiding supplementary costs, lost time and medical hazards for the patient and for the medical staff. PMID- 17282893 TI - Automatic MRI meningioma segmentation using estimation maximization. AB - With the advancement of the imaging facility and image processing technique, computer assisted surgical planning and image guided technology have become increasingly used in neurosurgery. For MRI has the characteristic of multi spectral image data., so knowledge-base techniques is widely used in brain MRI segmentation. Here we recognize the location of the tumor automatically and provide an accurate result by Estimation Maximization method. Simultaneously, promote the efficiency of reading image as well. PMID- 17282894 TI - Brain magnetic resonance images segmentation based on wavelet method. AB - This paper focused on the brain magnetic resonance (MR) images, which is one of the key problems in image processing. A novel segmentation method based on watershed transform and wavelets transform is presented for white matter in thin sliced single-channel brain magnetic resonance scans. The original image is smoothed by using anisotropic filter and over-segmented by the watershed algorithm. Finally, the brain MR image is segmented automatically by using the multicontext wavelets-based thresholding (MCWT) method. The result of the experiment indicates that the algorithm can obtain segmentation result fast and accurately. PMID- 17282895 TI - Modified Method for Classifying Crossing and Non-crossing Voxels in Fiber Reconstruction. AB - In solving intra-voxel fiber crossing problem in white matter fiber tracking, the classification of crossing and non-crossing regions seems essential and challenging. Although high Cpvalue is a usable indicator of intra voxel orientational heterogeneity, only using this metric is not accurate enough to decide exactly whether fiber crossing occurs as the lack of an exact and recognized threshold. In this paper, we present a new method which directly uses the orientation difference and the number of fibers that coexist in a single voxel as defining criterions to classify crossing and non-crossing voxels. Experiments with real DT-MRI data show higher accuracy and better adaptability with our new method. PMID- 17282896 TI - Relative dose distribution in gamma knife treatment near tissue inhomogeneties. AB - The primary goal in this study was to investigate 3-D dose distribution, near the areas of tissue inhomogeneities, in Gamma Knife Radiosurgery with the gel dosimetry. The spherical glass balloon of a diameter of 16 cm filled with the gel forms the homogeneous phantom; and an identical balloon with two corks placed on each side to represent the air cavities forms the inhomogeneous phantom. Dose calibration is performed by irradiating vials at known doses and then utilizing the R2- dose calibration curve. Stereotactic frames and fudicial markers were attached to the phantoms for MR scanning and image processing. Dose distributions from a single shot, using all 201 Cobalt sources, delivered to a known point with identical coordinates, are calculated both in homogeneous and inhomogeneous gel phantoms. In the aspect of dosimetrical quality control, the Gamma Knife planning system predicted dose distribution is compared with the experimental results. In the homogeneous phantom, the gel dosimetry calculated dose distribution is in good agreement with the GammaPlan predicted dose distribution. However, with the inhomogeneous phantom, the dose distribution is spatially different and significant differences in dose levels are observed. PMID- 17282897 TI - Fast computation of multiscale morphological operations for local contrast enhancement. AB - Poor local contrast is a nettlesome problem in biomedical image analysis. The multiscale method based on mathematical morphology has been successfully used in local contrast enhancement. However, the computational time is high. In this paper, the existing method is much improved by using few feature levels in an efficient way. The new algorithm is tested by experiments. Compared with the previous method, the results show that the proposed method is more effective, faster and less sensitive to noise. It is a fast and simple method for eliminating the non-uniformity of the intensities in images. PMID- 17282898 TI - An efficient lossless compression algorithm for FMRI data volume. AB - This paper presents an efficient lossless compression scheme designed for the fMRI data volume. An fMRI time series is composed of trend, noise and external stimulus response, which have different characteristics in wavelet domain. Reversible integer wavelet transform is applied to the fMRI time series. The smooth trend signals are extracted from the low frequency wavelet bands and they are coded by a lossy compression scheme. The lossy compression residual, noise, and other components are inversely transformed into time domain followed by adaptive clustering and then lossless coding. The experimental results show that the proposed method outperforms many existing schemes. PMID- 17282899 TI - Medical image registration based on mutual information using kriging probability density estimation. AB - This paper proposes a new approach of Kriging Estimation (KE) to the problem of probability density estimation, which is critical during the registration of medical images using Mutual Information (MI). The author proposed that the linear coefficients of Kriging Interpolation have "probability character" which makes them appropriate to be utilized in probability estimation. KE is a complement of existent probability estimation methods, the experiments provided have proved its efficacy. PMID- 17282900 TI - A 3D Adaptive Wiener Filter for Restoration of SPECT Images Using MRI as Reference Images. AB - Single Photon Emission Computed Tomography (SPECT) images suffer from poor resolution and low contrast, which make it difficult for physicians to put an accurate interpretation for diagnosis, in particular, early diagnosis. Although the Wiener filter is a simple and powerful tool to restore degraded images, the requirement for a priori information limits its application. In this paper, we present a new 3D adaptive Wiener filter for restoration of brain SPECT images with a priori data taken from a magnetic resonance imaging (MRI) of the same patient. The proposed algorithm automatically and significantly improve the contrast and sharpness of synthetic and real SPECT images while keeping amplification of noise under acceptable level. PMID- 17282901 TI - Fuzzy modelling of different tumorous cerebral tissues on MRI images based on fusion of feature information. AB - A fuzzy modelling approach is being proposed in this paper to estimate the model of tumorous cerebral tissues on MRI images. According to the graduality of description of neuro-radiologists, two tables have been combined to address two types of potential categories of glioma characteristics one is the array of different tissues versus gray level, and the other is the possibility of different tissues belonging to tumor. A hierarchical estimation structure has been proposed to estimate the models of tumorous cerebral tissues on MRI images by the fusion of this a priori knowledge. Through the model outline drawing, adjusting and parameters estimation, the result has shown that this is an efficient modelling method. PMID- 17282902 TI - An Over-Complete Independent Component Analysis (ICA) Approach to Magnetic Resonance Image Analysis. AB - This paper presents a new application of independent component analysis (ICA) in magnetic resonance (MR) image analysis. One of most successful applications for ICA-based approaches in MR imaging is functional MRI (fMRI) which basically deals with one-dimensional temporal signals. The ICA approach proposed in this paper is rather different and considers a set of MR images acquired by different pulse sequences as a 3-dimensional image cube and performs image analysis rather than signal analysis. One major difference between the fMRI- based ICA approaches and our proposed ICA-based image analysis is that the ICA used in the former is under complete as opposed to the latter which uses over-complete ICA. Such a fundamental difference results in completely different applications. PMID- 17282903 TI - Virtual mouse placenta: tissue layer segmentation. AB - Microscopic imaging is an important phenotyping tool to characterize the phenotype (e.g., morphology and behavior) change caused by genotype manipulation such as mutation and gene knockout. Recently we use high resolution microscopic imaging to study the morphological change on mouse placenta induced by retinoblast (Rb) gene knockout. In order to assess the morphological change we first segment each microscopic image into regions corresponding to different tissue types. Due to the complex structure of these tissues and large variation among the more than 2,000 images, we design a Bayesian supervised segmentation method which utilizing image features of all levels. The method has been applied to the entire data set and generated satisfactory results that is essential for further analysis on 3-D morphological change of the tissue types. PMID- 17282904 TI - Patient positioning error measurement based on dynamic template matching techniques. AB - The decrease of accuracy in patients' repeated positioning in radiotherapy due to body's transformation is considered and a positioning error measurement method using dynamic template matching technique is brought forward in this paper. This method is an improvement of the matching method to correct positioning error based on the CT digitally reconstructed radiograph(DRR), which uses the video reconstructed 3D surface model that can reflect the body's transformation as the matching template instead of DRR. This method can not only improve the positioning accuracy but also eliminate the adverse influence brought by body's transformation. PMID- 17282905 TI - Segmentation of LSCM Images based on Multi-channel Information Fusion. AB - The two channels of LSCM, the fluorescent light channel and the visible light channel, provide us with different modality images that contain special information respectively. In this paper we propose a new and integrated approach to segment images in the fluorescent light channel of LSCM, which have rather low SNR and can not provide sufficiently high intensity gradient at the boundary. Our approach, rather than relying on information of the velocity field alone, also includes statistical information of images in the visible light channel which provide subtle information of vessel structures. Information is described by corresponding image force. The approach is tested on LSCM images and experimental results show that it can segment low SNR vasculature structures automatically. Comparison is made between C-V model and the new approach, we find that the latter has better performance and can provide vasculature delineation with higher quality since information of both channels is utilized. PMID- 17282906 TI - Ground based nitrogen status of canola leaves using charged coupled device imaging sensor. AB - Rapid, non-destructive estimation of nitrogen content of crop is a potentially important application for both farm managers and researchers. This paper presents the development of a multi-spectral nitrogen deficiency sensor, which uses three channels (green, red, near-infrared) of crop images to estimate nitrogen level of the canola. The utility of a Charged Coupled Device Imaging Sensor for rapidly and nondestructively assessing foliar N status of canola was evaluated in two experiments. The sensors assess the nitrogen stress by means of the estimated SPAD value of the canola based on canola canopy reflectance sensed using three channels (green, red, near-infrared) of the multispectral camera. The core of this investigation is the calibration methods between the multi-spectral references and the nitrogen levels in crops measured using a SPAD 502 chlorophyll meter. Based on the results obtained from this study (The correlation was 0.89.), it can be concluded that a multi-spectral CCD camera can provide sufficient information to perform reasonable SPAD values estimation on-the-go during field operations. PMID- 17282907 TI - Wavelet lifting for speckle noise reduction in ultrasound images. AB - In this paper, a wavelet domain method for speckle noise filtering is presented. It uses non-decimated wavelet transform and Generalized Cross Validation thresholding technique. The spatial correlation of ultrasound speckle noise is broken by multiresolution analysis. Level dependent thresholding removes noise in the wavelet domain based on automatic estimation of noise energy in each subband. The efficacy of this filter is demonstrated on both simulated and real medical ultrasound images. The result is shown to be promising and outperforms other de noising approaches. A single adjustable parameter can be used by medical experts to balance the relevant image feature preservation and the speckle noise suppression. Lifting scheme as a way of constructing new biorthogonal wavelets based on existing wavelet as well as a way of performing wavelet transform is studied in this research to improve the performance of wavelet de-noising. PMID- 17282908 TI - Time-resolved noninvasive optical parameters determination in three-dimensional biological tissue using finite difference time domain analysis with nonuniform grids for diffusion equations. AB - The finite difference time domain (FDTD) analysis based on nonuniform grids for solving the diffusion equations in biological tissue has been proposed. It has been confirmed that the analysis greatly reduce the time for calculating time resolved reflectance in three-dimensional scattering medium preserving the numerical accuracies. Based on the analysis, noninvasive optical parameters determination in three-dimensional inhomogeneous medium divided into 192 homogeneous cubic cell 10 (mm) in edge lengths has been studied. Chi-square fitting for theoretical and experimental time-resolved reflectance was optimized by the downhill simplex method. As a result, it has been become clear that absorption coefficients in all cubic cells in scattering medium are estimated within the accuracy of 10% by utilizing only time-resolved reflectance. PMID- 17282909 TI - Reconstruction of tissue heterogeneity by near infrared imaging: a novel algorithm and benchtop validation. AB - A novel algorithm has been developed for Near Infrared (NIR) imaging of tissue optical properties with embedded heterogeneity. The algorithm was based on the optical measurements of the absorption perturbation by a matrix of multiple source detector pairs. Direct superimposition algorithm was used to calculate the two dimensional projected image of the tissue absorption. This absorption map is then compared with that of the homogenous phantom in order to reconstruct the absorption perturbation caused by the embedded object. Benchtop setup has been developed to validate this reconstruction scheme. Simulating tumors made of gelatin cylinders of high absorption coefficients were placed inside a homogenous intralipid phantom of specific background absorption. The depth of the tumor was adjusted at different levels and the diffuse reflectance was measured by a tissue imager consisting of a matrix of 4 sources and 4 detectors. The measured absorption coefficients were compared with the actual tumor absorption coefficients at different tumor depths in order to determine the reconstruction accuracy. PMID- 17282910 TI - Transcutaneous fluorescent imaging with a depth-dependent point spread function. AB - The transcutaneous fluorescent imaging (TFI) method was applied to the imaging of a small experimental animal such as a rat. The feasibility of the functional imaging in TFI was verified. To make this method more practical, a technique of scattering suppression was proposed. The depth-dependent PSF was derived as an analytical solution in a closed form. The applicability of this technique to the functional TFI and its usefulness were demonstrated in animal experiments. PMID- 17282911 TI - A method for measurement of water temperature in micro-region using near infrared light. AB - We have proposed a method for non-invasively measuring the temperature changes of water in a micro-region using near infrared (NIR) light. The goal of this study is to measure the temperature changes of biological cells or tissues. This method is on the basis of the phenomenon that the NIR absorption spectrum of water depends on temperature. First, in order to confirm whether a right irradiation for the temperature measurement itself affects the water temperature, we calculated the temperature rise caused by the optical absorption. Next, absorbance spectra in the wavelength range of 1300 - 2000 nm of water with a thickness of 100 and 500 m were measured by a micro-spectrometer. The measured spectra with temperature-dependence were calibrated using a regression analysis. The standard error of calibration was 0.6 C for 100 m-thickness. PMID- 17282912 TI - A New Approach to Detect Soil Nutrient Content Based on NIR Spectroscopy Technique. AB - The objective of this research was to evaluate the prediction ability of NIR to soil nutrient content. A total of 165 soil samples were obtained from the field and analyzed their spectra features. 135 samples spectra were used during the calibration and cross-validation stage, 30 samples spectra were used to predict N, P, K and OM concentration. NIR spectra and constituents were related using partial least square regression (PLSR) technique. The r between measured and predicted values of N and OM, were 0.92 and 0.93 respectively, demonstrated that NIRS have potential to predict accurately this constituents in this soil, not being this way in the prediction of P and K with r, 0.48 and 0.68 respectively, demonstrated a poorly for P and a less successfully for K prediction. The result also shows that NIR could be a good tool to be combined with precision farming application. PMID- 17282913 TI - Simulating fluorescent microscope images of cell populations. AB - High-throughput cell measurement techniques producing images of cell populations have raised a need for accurate automated image analysis methods. Validating the analysis methods used for automated cytometry is an issue yet to be solved. Manual validation, being an exhaustively laborious task, enables comparison but does not provide solution for large scale analysis. By creating a parametric model for cell shape, and simulating images of cell populations including errors and aberrations caused by the measurement system, validation of different image analysis methods is enabled. As a result, studies with large populations, where the number of cells and many other key parameters are user-tunable, can be carried out by using simulated cell population images. The cell image simulator, as well as validation case studies for segmentation and image restoration are presented. PMID- 17282914 TI - Backpropagation Neural Network for Motion Analysis on Blood-pool Gated Single Photon Emission Computed Tomography. AB - We used backpropagation neural network for left ventricular motion analysis on Tc 99m labeled RBC blood-pool gated single photon emission computed tomography (GSPECT). Phantom images by the model of solid spheres were generated to simulate the left ventricle. Training data sets were selected from the phantom images. After training, the neural network can perform motion analysis on the phantom images and all series of patients' GSPECT images. The results of motion analysis were displayed in the formats of vector fields superimposed on the original GSPECT images. The GSPECT of one patient with normal left ventricle and two patients with abnormal left ventricular motion were acquired and analyzed. The study showed that back propagation neural network was useful in the evaluation of left ventricular motion in GSPECT images. PMID- 17282915 TI - Averaged properties of articular cartilage from multidisciplinary microscopic imaging study. AB - Most microscopic imaging techniques do not have the resolution to visualize individual collagen fibrils in articular cartilage, which possesses unique depth dependent anisotropy and noticeable topographical heterogeneity. These imaging studies therefore deal with the averaged properties of the tissue. In this report, an ellipse model is introduced to explore the common connections between the anisotropic features of the tissue and the measurable quantities in several imaging techniques, including microscopic magnetic resonance imaging (µMRI), polarized light microscopy (PLM), and transmission electron microscopy (TEM). This model uses three quantities to represent the averaged properties of the tissue: the concentration ƿ that describes the density of the measurable property, the overall orientation Θ that describes the angular dependent features in the tissue, and the anisotropy Ɛ that describes the coherence of the measurable objects. We conclude that this ellipse model may serve as a useful platform to explore the common connections among different imaging results. PMID- 17282917 TI - Design and Evaluation of Surgical Navigation for Anterior Cruciate Ligament Reconstruction using Autostereoscopic Image Overlay of Integral Videography. AB - This paper describes a surgical navigation system for anterior cruciate ligament (ACL) reconstruction using an autostereoscopic image overlay technique. We superimpose a real three-dimensional (3-D) image onto the patient for image guided therapy. The images are created by employing an animated visualization of integral videography (IV). IV records and reproduces 3-D images using a micro convex lens array and flat display; it can display geometrically accurate 3-D autostereoscopic images and reproduce motion parallax without the need for any special viewing or tracking devices. The use of semi-transparent display devices makes it appear that the 3-D image is inside the patient's body, which enables viewing the structure of ACL and detecting the position of femur, tibia and surgical tools. This is the first report of applying an autostereoscopic display with an image overlay system in ACL reconstruction surgery. Experiments demonstrated that the patient-image registration method and the fast IV rendering technique produce an average registration accuracy of 1.16 mm and frame rate of IV image display about 3 frames and 11 frames per second for organ and surgical tools respectively. PMID- 17282916 TI - Visualization technique for water content distribution of skin tissue by dualband polarization imaging. AB - The advanced imaging technique for visualizing two-dimensional water content distribution in the stratum corneum of human skin is proposed. The method involves two elemental principles of spectral filtering and imaging with polarization control. It is found in the in vivo experiment in the visible and the near-infrared range that the reflectance spectra of skin tissue in the wavelength range shorter than 600 nm are affected largely by water content. The polarization imaging technique is, on the other hand, introduced for emphasizing the subsurface reflection from skin tissue. The superficial reflection can be separated from the deeply penetrated light by controlling the orientations of the polarizer and the analyzing polarizer put in front of the light source and the imaging device, respectively. The combination of spectral bandpass filtering and polarization imaging enables us to acquire the water content distribution of the stratum corneum. PMID- 17282918 TI - Aberration estimation from single point image in a simulated adaptive optics system. AB - Adaptive optics has been recently applied for the development of ophthalmic devices, with the main objective of obtaining higher resolution images for diagnostic purposes or ideally correcting high-order eye aberrations. The core of every adaptive optics systems is an optical device that is able to modify the wavefront shape of the light entering a system: once the shape of the incoming wavefront has been estimated, by means of this device it is possible to correct the aberrations introduced along the optical path. The aim of this paper is to demonstrate the feasibility, although in a simulated system, of estimating and correcting the wavefront shape simply by means of an iterative software analysis of a single point source image, thus avoiding expensive wavefront sensors or the burdensome computation of the PSF of the optical system. To test the proposed algorithm, a simple optical system has been simulated with a ray-tracing software and a program to estimate the Zernike coefficients of the simulated aberration from the analysis of the source image has been developed. Numerical indexes were used to evaluate the capability of the software of correctly estimating the Zernike coefficients. Even if only defocus, astigmatism and coma were considered, the very satisfactory results obtained confirm the soundness of this new approach and encourage further work in this direction, in order to develop a system able to estimate also spherical aberration, tilt and field curvature. An implementation of this aberration estimation in a real AO system is also currently in progress. PMID- 17282919 TI - On the small vessel detection in high resolution retinal images. AB - In this paper, we proposed a new scheme for detection of small blood vessels in retinal images. A novel filter called Gabor Variance Filter and a modified histogram equalization technique are developed to enhance the contrast between vessels and background. Vessel segmentation is then performed on the enhanced map using thresholding and branch pruning based on the vessel structures. The experiments on high resolution images showed the desirable results with performance of 84.75% true positive rate and 0.15% false positive rate. PMID- 17282920 TI - Dynamic properties of human eyes. AB - This paper presents novel details on the dynamic behavior of human eyes (see Fig.1). A high speed camera is used to capture the movement of the eye surface, which is excited by an air jet. For one group of subjects the dynamic respose of the eyes ends shortly after the air jet stops. For another group of subjects a distinct offset in the displacement remains, which takes a significantly longer time to vanish. The two distinct phases in the eye movement are the result of the dynamic response of the cornea and the total eye, respectively. A deeper understanding of the eye dynamics is important for obtaining a higher reliability of diagnostic tools for glaucoma. PMID- 17282921 TI - Coregistration of fNIRS Data on to the Realistic Head Model. AB - In this paper, we propose a method to visualize fNIRS(Functional Near Infrared Spectroscopy) data on a realistic head model. In order to illustrate the success of this study, we used fNIRS data obtained during the Stroop task. For the realistic head model, high resolution T1 weighted MR images are used. Preliminary results show that proposed method will be usefull for visualization of fNIRS data and also these results are correlated with EEG (Electroencephalogram) topograpghic mapping for the same Stroop Task. PMID- 17282922 TI - A Fast Center of Pupil Detection Algorithm for VOG-Based Eye Movement Tracking. AB - This paper proposes an algorithm that has been developed for the video-oculograph method. It is used to detect the center of the pupil, extracted from a captured image of an eye acquired by using a CCD camera and a computer with image grabber. The captured eye image is 640 by 480 pixels in size at 8 bits per pixel, in depth. The center of the pupil area could be obtained by applying the proposed algorithms for the threshold of the captured gray-scale image, for image enhancement and noise removing techniques even though the pupil area was partially covered by eyelashes and an eyelid. PMID- 17282923 TI - Development of Linearly Polarized Optical Coherence Tomography and the measurement on Porcine Tendon Birefringence. AB - A novel polarization-sensitive optical coherence tomography (PS-OCT) using only linearly polarized light is proposed. To compare with conventional PS-OCT which use circular polarized incident light, linear PS-OCT shows three advantages: (1) in a turbid medium with linear birefringence, the degree of polarization of backscattered light for linearly incident light dose not change significantly; (2) Phase retardation (PR) of the sample can be obtained totally from the phase difference between the polarization heterodyne signals, thus common phase noise rejection mode is introduced inherently. These advantages lead to the immunity of background phase noise and laser frequency noise simultaneously, and also lead to the better sensitivity of PR measurements; (3) the dynamic range of PR in this system is between 0° to 180°, which is two times larger than that of conventional circular PS-OCT. PMID- 17282924 TI - The study on computer aided peripheral visual field diagnosis. AB - Background Despite the widespread adoption of automated perimetry, there is still a role for peripheral perimetry. So far there was no accurate quantitative analysis on the change of visual field, most analysis were qualitative and depend on doctor's experience. Method Computer aided diagnose system was designed to judge the accurate change in visual field. Tabu Seach technology was used to identify visual field from the result of Peripheral perimeter test, and accurate visual filed defect dimension can be concluded by compared with point to point. At the same time liable eye diseases were predicted by computer. Conclusion Computer aided peripheral visual field diagnose system can identify defect in visual field, and provide reliable clinical diagnosis. Key words peripheral visual field, Computer aided diagnose, tabu search. PMID- 17282925 TI - Automatic measurement of intervertebral movements using radiographic images. AB - Measurement of intervertebral movements is essential in the assessment and diagnosis of patient's instability. However, diagnosis of the underlying causes remains problematic despite of extensive study. Reasons for this arise from the variability of detecting vertebral body landmarks, labor and time-consuming of manual point placement, incompletely description of the vertebral body shape and also from the structural complexity of the spine. In this study, the precision and accuracy of a new automatic method for morphometry of intervertebral movements were estimated. Active Contour is a key feature of segmentation and provides rapid and accurate measurement of vertebral shape. Fourier descriptors are used to represent the vertebral shapes. Genetic Algorithm (GA) is then applied to determine the spinal kinematics. Reproducible and reliable determinations of the intervertebral movements of the lumbosacral spine, when performing Flexion-Extension motions, are addressed. This paper describes the accuracy and feasibility of an active shape model (ASM) and Genetic Algorithm (GA) to measure spine kinematics. PMID- 17282926 TI - A novel 3D finite element modeling based on medical image for intervertebral disc biomechanical analysis. AB - In order to study the biomechanical mechanism properties of intervertebral disc herniation, combining the CT and MRI data-based anatomical structure of spine. A three-dimensional geometric model of the lumber disk was constructed. Based on the geometric model, a three-dimensional finite element modeling (FEM) for biomechanical analysis has been created. The FEM will represents a promising tool in clinical diagnosis and optimizing individual therapy in the intervertibral disc herniation. PMID- 17282927 TI - Image Registration in Intra-oral Radiography. AB - Image registration is one of the image processing methods which is widely used in computer vision, pattern recognition, and medical imaging. In digital subtraction radiography, image registration is one of the important prerequisites to match the reference and subsequent images. In this paper, we propose an automatic non rigid registration method namely curvature-based registration that relies on a curvature based penalizing term and its application on dental radiography. The regularizing term of this intensity-based registration approach provides affine linear transformation so that pre-registration step is no longer necessary. This leads to faster and more reliable solutions. The implementation of this approach is based on the numerical solution of the underlying Euler-Lagrange equations. In addition, a comparison between this algorithm and Linear Alignment Method (LAM) with 20 image pairs is presented. PMID- 17282928 TI - Shape Analysis of Breast Masses in Mammograms via the Fractal Dimension. AB - Masses due to benign breast diseases and tumors due to breast cancer present significantly different shapes on mammograms. In general, malignant tumors appear with rough and complex boundaries or contours, whereas benign masses present smooth, round, or oval contours. Fractal analysis may be used to derive shape features to perform pattern classification of breast masses and tumors. Several procedures have been proposed to compute the fractal dimension of various types of objects or regions of interest in biomedical images, among which the box counting and ruler methods are popular. In this study, we applied the two methods mentioned above to compute the fractal dimension of both the two-dimensional (2D) contours of breast masses and tumors, as well as their one-dimensional (1D) signatures. A comparative analysis was performed to assess the performance of the two methods of computing the fractal dimension and the two methods of representing the boundaries of masses. It was observed that analysis of the 2D contour representation with the ruler method resulted in the highest classification accuracy of up to 0.946, as indicated by the area under the receiver operating characteristics (ROC) curve. The results indicate that the fractal dimension can serve as a good shape feature for the benign-versus malignant classification of breast masses in mammograms. PMID- 17282929 TI - Computing shortest cycles on discrete surfaces for acurate topological modifications of medical image isosurfaces. AB - Topological control over discrete isosurface is of primordial interest in medical applications, especially discrete model building for active contours. Previous attempts showed that the key point in acurately modifying topology was computation of shortest cycles on the surface of interest. This paper generalizes the shortest path algorithm to compute shortest cycles in a given homotopy class on a discrete surface with arbitrary topology. The algorithm is simple to implement and general to all kinds of discrete surfaces. The algorithm is validated against synthetic surfaces. PMID- 17282930 TI - Image-based electronic patient records for secured collaborative medical applications. AB - We developed a Web-based system to interactively display image-based electronic patient records (EPR) for secured intranet and Internet collaborative medical applications. The system consists of four major components: EPR DICOM gateway (EPR-GW), Image-based EPR repository server (EPR-Server), Web Server and EPR DICOM viewer (EPR-Viewer). In the EPR-GW and EPR-Viewer, the security modules of Digital Signature and Authentication are integrated to perform the security processing on the EPR data with integrity and authenticity. The privacy of EPR in data communication and exchanging is provided by SSL/TLS-based secure communication. This presentation gave a new approach to create and manage image based EPR from actual patient records, and also presented a way to use Web technology and DICOM standard to build an open architecture for collaborative medical applications. PMID- 17282931 TI - Web Based Nasal Surgical Simulator Using VRML and Java. AB - This paper describes a nasal surgical simulator that we have designed and implemented to run on the WWW using VRML and Java. In this paper we concentrate on implementation details such as collision detection and the usage of our simulator. At last, we discuss the advantage and disadvantave of the simulator. PMID- 17282932 TI - Automatic contouring for breast tumors in 2-d sonography. AB - Automatic contouring for breast tumors using medical ultrasound (US) imaging may assist physicians, without relevant experience, in making correct diagnoses. This study utilizes the watershed transform and active contour model (ACM) to overcome the natural properties of US images, speckle, noise and tissue-related textures, to segment the breast tumors precisely. The watershed transform is performed as the automatic initial contouring procedure to maintain a rough tumor shape and boundary. Next, ACM automatically determines the exquisite contours of the tumor. The results of computer simulations reveal that the proposed method always identified similar contours and regions-of-interest (ROI) as were obtained by manual contouring (by an experienced physician) of the breast tumor in US images. As ultrasound imaging becomes more widespread, a functional automatic contouring is essential to clinical application. In computer-aided diagnosis (CAD) applications, moreover, automatic contouring can save much of the time required to sketch a precise contour, with very high stability. PMID- 17282933 TI - A Method for Characteristic Extraction of Ultrasound Doppler Signal with Peak valley Relationship under Heavy Noise. AB - This paper proposes a real-time algorithm estimating clinical useful parameters from the maximum frequency curve of ultrasound Doppler spectrum. Traditional methods always apply some pre-calculations to the frequency waveform, for instance, filtering or scaling transformation, which have limitations on real time features detection and waveform display. In this paper, we propose and maintain a process unit as a section of the waveform with the help of its phase information and the idea of the changeable scaling in the wavelet, to determine the Doppler waveform parameters in real time. From a set of in vivo Doppler waveforms, our proposed algorithm can pick up right parameters even in very noisy environment. PMID- 17282934 TI - The correlation-based algorithm to perfusion assessment in ultrasound image. AB - A high frequency contrast-assisted destruction/reperfusion imaging system has been developed to improve image resolution in previous study. Our goal in this work is to build a fast and robust algorithm to evaluate volumetric microcirculation blood flow. The microcirculation flow rate is determined by the multiplication of perfusion area and corresponding blood flow velocity mapping. The blood flow velocity can be estimated from B-mode time-intensity curves (TICs). Two new methods, correlation-based approach (CBA) and sum-absolute difference approach (SADA), are proposed to locate and assess perfusion area. In vitro experiments were introduced to test the performance of two approaches. The results indicate a good correlation between the actual flow rate and the estimated volumetric flow rate. Potential applications of this blood flow estimation method include high-resolution flow assessment in small animal tumor and glaucoma models and the evaluation of superficial vasculature in clinical studies. PMID- 17282935 TI - Non-rigid Registration Algorithm Based on Modally Controlled Free Form Deformation. AB - To register pre-operative MRI/CT images with intra-operative ultrasound images based on the vessels visible in both of the modalities, we presents a non-rigid registration method of multimodal medical images based on Free Form Deformation was proposed. When the images are aligned, the centerline points of the vessels in one image will align with the intensity ridge points in the other image. Rigid transformation was adopted in global registration while local deformation was described by a free form deformation (FFD) based on a modally controlled B spline. The method applies an optimization strategy combining the genetic algorithm with the conjugated gradients algorithm to minimize the objective function. Two experiments were designed on phantom and clinical data to evaluate the method. The results indicate that the registration method is consistent and suggest that it is accurate. The average standard deviation of the final transformation parameters is sub-voxel, sub-millimeter, and within 0.010 radians. The results show that the method has good registration accuracy and convergence rate. And it can be applied efficiently in the ultrasound-image-guided surgery system. PMID- 17282936 TI - Organ segmentation using atlas registration and fuzzy connectedness. AB - In this paper, a framework combining the atlas registration and the fuzzy connectedness for the automatic segmentation of abdominal organs is proposed. First, a pre-labeled atlas is registered onto the subject to establish the proper correspondence between the atlas and subject. Second, we utilize the fuzzy connectedness framework to segment organs of interest from the subject image. Taking advantage of the correspondences between atlas and subject, common interactive or empirical specification of fuzzy connectedness parameters are replaced by automatic and subject-oriented specification. The performance of the proposed method has been qualitatively validated on CT and MRI images with manual segmentation as ground truth. Results have shown the versatility of this method in segmenting images of different modalities. This automatic method is expected to find wide applications in 3D visualization, radiation treatments planning, and medical database construction. PMID- 17282937 TI - Feature analysis of brain MRI images based on fractal dimension. AB - Fractal dimension has been widely used in the process of medical images measurement and analysis. A novel fractal dimension based on triangular prism surface area (TPSA), is introduced to two-dimensional medical images in this article. A series of tests show that this method is accurate and robust in operation. Applying the TPSA method to analyzing the feature characteristics of brain MRI images, tests show that: compared with the normal brain MRI images, fractal dimensions of the abnormal brain images become less. As a result, it is suggested that fractal dimension be one of guidelines in diagnosing some brain diseases. PMID- 17282939 TI - Breast Tissue Density and CAD Cancer Detection in Digital Mammography. AB - This study is part of the research of improving early detection of breast cancer in screening mammograms by focusing on computerized analysis and detection of cancers missed by radiologists. It is directed to the analysis of breast density in missed cancer cases and the effect of tissue density on cancer detection. A total of 100 missed cancer cases were collected which were used to generate three different datasets including mammograms with missed cancer, mammograms with screening-detected cancer and normal mammograms. A statistical-based method was applied to segment the breast density tissue. The percentage of the segmented density tissue area out of the whole breast area is calculated as the index of breast density. A set of tests was applied to examine (1) the differences in density between the mammograms at the detected stage and that at missed stage, (2) the density difference between the normal mammograms and the cancerous mammograms; (3) the effect of breast density on CAD cancer detection. The results demonstrate that (1) no significant difference in breast density between the detected and missed stages; (2) the density of cancerous mammograms is significantly higher than normal mammograms; (3) similar to mammogram screening by radiologists, the lesions occurred in dense breasts are more likely to be missed in CAD detection especially at their early stage. PMID- 17282938 TI - Detection of Cerebral Vessels in MRA Using 3D Steerable Filters. AB - This paper describes a fully automatic method for enhancement and segmentation of three-dimensional(3D) cerebral vessels in MRA. We obtain the 3D dyadic B-spline wavelets by extending corresponding 1D wavelet. A 3D steerable filter is then developed based on 3D dyadic B-spline wavelets. One can adaptively steer the filter to an arbitrary direction. The oriented energy of filter response is introduced for detecting orientation strength of vessels in that direction. The points with maximum of local oriented energy across multiple scales are regarded as vessel points. This method was tested on real MRA data and promising results have been obtained. It could be suitable for other types of curvilinear structures such as cardiovascular vessels, bronchial tree. PMID- 17282940 TI - A Relative Thoracic Cage Coordinate System for Localizing the Thoracic Organs in Chest CT Volume Data. AB - Thoracic organ segmentation from the three dimensional (3D) medical images always needs an initial position. We developed a relative thoracic cage coordinate system (RTCCS) for localizing the organs in chest CT volume data. To test the RTCCS, we first extracted the 3D ribs and heart-wall from the segmented atlas of male American visible human, and then we built up a RTCCS according to the position of the ribs and calculated the relative coordinate values of all the voxels in the heart-wall. Next we segmented the 3D ribs from the female American visible human CT data and built up another RTCCS on these ribs. At last we used the relative coordinate values of the male visible human's heart-wall to reconstruct a new 3D heart-wall in the thoracic cage of the female visible human CT data, getting an approximate position of the female visible human's heart. PMID- 17282941 TI - The preliminary study of differentiating osteoporotic fractured group from nonfractured group. AB - Osteoporosis is characterized by an abnormal loss of bone mineral content, which leads to a tendency to nontraumatic bone fractures or to structural deformations of bone. Thus bone density measurement has been considered as a most reliable method to assess bone fracture risk due to osteoporosis. In past decades bone texture measures have been also studied in connection with the bone quality estimation. However, most studies have been focused on texture analysis of CT or MR images. Though studies on plain radiographs have been also performed to assess in vivo trabecular structure these studies are mainly done on anatomic sites such as femur, spine, and calcaneus. In this preliminary study we apply various texture measures to distal radius plain radiographs and point out several promising texture measures that significantly distinguish between osteoporotic fractured group and nonfractured group. PMID- 17282942 TI - Learning-based Method for P53 Immunohistochemically Stained Cell Image Segmentation. AB - In this study, a learning-based color image conversion method is proposed for cell image segmentation. Firstly, we demonstrate that minimum distance-based pixel classification, such as clustering, for color image segmentation in the color space is equivalent to thresholding grayscale images. Motivated by this result, we develop the so called C-G-T procedure for color image segmentation, where color image (C) is first converted into grayscale (G) and thresholding (T) is then performed on the gray image to segment objects out of background. The transform for image conversion is learned from the global pixel distribution in the color space, while the threshold is learned from local pixel distribution of the gray image. The combination of global and local learning makes the C-G- T procedure adaptive and computational efficient. Extensive experiments are performed to verify the effectiveness of our method. PMID- 17282944 TI - A hybrid algorithm for medical image registration. AB - Registration is a process to align different acquired images of the same subject. A major problem in this field is to register images captured by different imaging systems. These images have different gray values so simple methods like correlation are not applicable. In this paper automated registration of CT and MR head images is studied. It is assumed that images are only of relative translation and rotation. The proposed method includes two stages. First, feature extraction of CT and MR images, (should be extractable and constant in both imaging systems). Second, feature alignment which is moment-based. The results confirm the accuracy and robustness of the proposed method. PMID- 17282943 TI - Finite Element Modelling of Breast Biomechanics: Finding a Reference aState. AB - Non-rigid-body registration techniques, that constrain the set of possible soft tissue deformations to be consistent with the basic laws of physics, offer a means of providing realistic and accurate estimates of breast movement under mammographic compression. Such constraints can be imposed by the use of anatomically accurate finite element models that predict soft tissue deformations. The overarching aim is to develop tools for tracking regions of interest across multiple images (different views taken at different times) for image-guided surgeries and reliable diagnostic and therapy monitoring. Due to the nonlinear deformations imposed on the breast under the various imaging modalities, the finite element reference geometry from which deformations are predicted is important. Gravity loads act on the breast in all imaging modalities. In this paper, we propose a method of identifying a stress-free reference state of the breast given a series of loaded deformed configurations that have been derived from images of a patient placed in different orientations with respect to the direction of gravity. PMID- 17282946 TI - Performance Evaluation of Abdominal Fat Burden Quantification in CT. AB - Abdominal fat accumulation is an important cardiovascular risk ovascular risk factor. In clinical practice, delineation of subcutaneous and visceral fat is performed manually by an expert. This procedure is labor intensive, time consuming, and subject to inter-and intra-observer variability. In this paper, we present an extension of our previous work on automatic fat burden quantification and classification. Our improved method automatically differentiates abdominal fat into subcutaneous and visceral fat components and removes equipment-related artifacts. We evaluated the performance of our method using data from 40 subjects with very encouraging results. PMID- 17282945 TI - Evaluation and initial validation studies of anatomical structure morphing. AB - Anatomical Structure Morphing is the process of estimating the patient-specific 3D shape of a given anatomy from a few digitized surface points. This provides an appropriate riate intra-operative 3D visualization without pre oroperativeintra- perative imaging. Our method fits a statistical deformable model to the digitized landmarks and bone surface points which are usually sparse. The statistical deformable model is constructed using Principal Component Analysis (PCA) from an appropriate training set of objects. Our proposed technique extrapolates the 3D shape by computing a Mahalanobis distance weighted least-squares fit of this model to the minimal sparse 3D data. In this paper we present evaluation and initial validation studies of our morphing technique on 9 dry cadaver femur bones. The influence of size of the initial training set on the morphing performance is also evaluated by repeating our experiments on two different training sets of varying sizes. PMID- 17282947 TI - 3-d optic disk reconstruction via combined registration and inclusion of eye optical effects. AB - This paper describes a method of three-dimensional (3-D) optic disk reconstruction from a pair of stereo images. This is achieved through the implementation of various procedures that further enhance the accuracy including camera calibration, constraint-based combined registration, dense-depth recovery, and eye-optics inclusion. A combination of two registration methods is applied to precisely detect the correspondences, which are then converted into depths. The optical effect of light media within the eyeball is considered. A new method is proposed to calibrate and integrate this effect into the reconstruction process to provide an accurate 3-D image of optic disk. Compared with the result from Heidelberg Retina Tomograph (HRT), the 3-D image reconstructed by the proposed method shows good consistency and compatibility which indicates that it could be used as an alternative mode of 3-D viewing of the optic nerve head. PMID- 17282948 TI - Average row thresholding method for mammogram segmentation. AB - Two novel threshold techniques are proposed for image segmentation which is a very critical task in any image processing. The two methods are based in scanning each image row by row and to find the proper threshold value. A modification of this method is developed to find the threshold value by average. The two methods are implemented on a mammogram and accordingly, a comparison between the two methods is carried out. PMID- 17282949 TI - 3D Reconstruction Using Image Contour Data Structure. AB - Fast and accurate 3D object reconstruction from 2D image slices represents a difficult and challenging problem. Scientists have to either manually define the boundary of the partial object which is time consuming and may lack accuracy or provide the object boundary data which requires all objects be segmented. In this paper, we propose a new method for 3D reconstruction based on optimal image contour mapping. We also propose a novel date structure to represent the corresponding 3D objects. In our approach, all object contours in the same slice as well as adjacent slices are automatically segmented and combined in a hierarchical tree data structure. This data structure allows fast 3D object retrieval and 3D component analysis. PMID- 17282950 TI - Liver tumor volume estimation by semi-automatic segmentation method. AB - Liver cancer is one of the most popular cancer diseases and causes a large amount of death every year. In order to make decisions such as liver resections, doctors will need to know the tumor volume, and further, the functional liver volume. Thus, an important task in radiology is the determination of tumor volume. Accurate segmentation of liver tumor from an abdominal image is one of the most important steps in 3D representation for liver volume measurement, liver transplant, and treatment planning[1]. Since manual segmenation is inconvenient, time consuming and depends on the individual operator to a large extent, automatic segmentation is much more preferred. In this paper, an active contour model is used to segment tumors from CT abdominal images. Initial boundary is manually placed by operators outside the tumor region. The snake deforms to the tumor boundary with the minimization of energy function. We then calculate the tumor volume using the series of segmented tumor slices. Results show that this method is quite efficient in tumor volume estimation compared with the WHO criteria, which measures the tumor by multiplying the longest perpendicular diameters. PMID- 17282951 TI - An Enhanced LBP Feature Based on Facial Expression Recognition. AB - Because of excellent capability of description of local texture, Local Binary Patterns (LBP) have been applied in many areas. In this paper, we enhance the classical LBP method from three aspects for facial expression recognition: image data, extracting features and the way of combining all these features. At first, we adopt wavelet to decomposed images into four kinds of frequency images from which the features are extracted to increase original data. Then we extract LBP features with a new local and holistic way to make features more robust. At last, in order to use the extracted features more logical, we combine all data in an adaptive weight mechanism. All experiments are also proved that the proposed improvements in this paper have promoted the performance of facial expression recognition greatly. PMID- 17282952 TI - Watershed segmentation of detected masses in digital mammograms. AB - A method for segmentation of detected masses in digital mammograms is introduced. The method is based on gray scale mathematical morphology. In a preprocessing step, image enhancement based on a local histogram technique is applied, followed by a morphological smoothing operation. The watershed transform is then applied to the gradient of the smoothed image resulting in segmented regions. A good segmentation is important in order to be able to extract useful feature measures from the segmented regions. These feature measures can be input to a classifier which classifies each region as either a mass or a false detection. Initial experiments have been performed using mammograms from the MIAS database. Results of the experimental study indicate that our scheme can provide useful contour extraction for mass structures. PMID- 17282953 TI - Medical image clustering for intelligent decision support. AB - Image mining is more than just an extension of data mining to image domain but an interdisciplinary endeavor. Very few people have systematically investigated this field. Clustering medical images for intelligent decision support is an important part in domain-specific application image mining because there are several technical aspects which make this problem challenging. In this paper, we firstly quantify the domain knowledge about brain image, and then incorporate this quantified measurement into the clustering algorithm. Our algorithm contains two parts: (1) clustering regions of interest (ROI) detected from brain image; (2) clustering images based on the similarity of ROI. We apply the method to cluster brain images and present results to demonstrate its usefulness and effectiveness. PMID- 17282954 TI - A computer-aided oral implantology system. AB - In order to optimize the position of oral implants and make the best possible use of the available bone volume in the oral implant therapy, a computer-aided oral implantology system including the framework, modeling, preoperative 3D planning, registration method, optical tracking systems and real-time navigation is introduced in this study. With the support of this system, the precision achieved in the planning phase can be transferred to the patient so that the accuracy of the oral implant surgery is improved. PMID- 17282955 TI - Reconstruction of Vessel Axis Based on the Matching of iterative Projection Algorithm and Analysis of Corresponding Points. AB - This paper proposes a novel method of Reconstruction of Vessel Axis on the matching of iterative projection algorithm and analyzing of corresponding points. The 3-D space is divided into several cubes. The cubes are projected in the actual projection directions separately. If a cube-projection includes vessel axis points, it is believed that the cube includes 3-D vessel. Then we divide the cube into several smaller cubes and repeat above process until the needed precision is reached. An approximate 3-D model of vessel axis is constituted according to projections of the cubs. The corresponding relationships of vessel axis between different direction projections are analyzed according to the approximate 3-D axis model. Then we can constitute the accurate continuous 3-D vessel axis by interpolation method. We use an actual DSA sequence as the experimental data and the result is satisfactory. PMID- 17282956 TI - Discrimination between two lung diseases using chest radiographs. AB - Economic considerations make the conventional chest radiograph (X-ray) film an important ingredient in the diagnostic process. An initial clinical investigation for patients with suspected lung ailments is the study of the chest X-rays. The problem of detection for diseases in their early stages are well known using X ray. A technique involving wavelets coefficient as the feature vector and Andrew's Curve has been proposed for detection of Mycobacterium Tuberculosis (MTB). This paper presents new and important results whereby lung cancer (LC) may be detected and differentiated from MTB. A method to calculate misclassification probabilities is given. PMID- 17282957 TI - Segmenting and counting of wall-pasted cells based on gabor filter. AB - Correctly counting the live cells plays a great role in the ectogenetic anti virus experiment. According to the irregular shape and arbitrary size of the wall pasted Hela cells overlapping each other, we propose a scheme to segment and count the cells using Gabor filter with different parameters and Morphological operation. Experiments reveal that filters with different parameters will lead to different results and a better segmentation will be achieved based on the characteristics of cells and optimal parameters. Large amount of experiment results show that this algorithm can successfully segment the cells and the accuracy arrives at 99.3%. This scheme based on image analysis and pattern recognition can overcome some disadvantages of traditional approaches, shortening anti-virus experimental period and reducing experimental cost. PMID- 17282958 TI - Cortical vascular blood flow pattern by laser speckle imaging. AB - The cor tical vascular blood flow pattern is associated with the functional response in cerebral cortex. The pattern of the vascular blood flow can be used to study the spatiotemporal activities of the somatosensory center and the diagnosis of the focal stroke or ischemia. In this present study, tempor al laser speckle analysis is used to obtain the cortical blood flow information. By centerline modeling method based on ridge tracking, we extracted the cortical vessels. By fusing with the laser speckle contrast results, we obtained the image of the cortical vascular blood flow pattern in which both the vessels and the blood velocity can be visualized. PMID- 17282959 TI - Active contours with automatic initialization for myocardial perfusion analysis. AB - Quantitative analysis of myocardial perfusion requires detection of myocardial boundaries in many short-axis MR images. Manual tracing of myocardial boundaries is a time-consuming and tedious task, which may limit the clinical use of quantitative analysis. In this paper, we propose an automatic detection algorithmbased on active contours. For initialization, starting contours need to be defined. Instead of manually tracing the initial contours, our approach presents an automatic method for finding initial contours of epicardium and endocardium. Once the initial contours are defined, we apply the active contours called stochastic active contour scheme (STACS) for image segmentation. PMID- 17282960 TI - The effect of color correction of endoscopy images for quantitative analysis in endometrium. AB - The objective of this study was to develop a standardized protocol for the capturing and analysis of endoscopy digital images for subsequent use in a Computer Aided Diagnosis (CAD) system in gynaecological cancer. Images were captured at optimum illumination and focus at 720x576 pixels using 24 bits color in the following cases: (i) for a variety of testing targets from a color palette with known color distribution, (ii) different viewing angles and distances from calf endometrium, and (iii) images from the human endometrium. Images were then gamma corrected and their classification performance was compared against that of nonqamma corrected images. No significant difference in texture features was found between the close up and panoramic views, and between angles, either before or after gamma correction. There was significant difference in certain texture features between normal and abnormal endometrium, both before and after gamma correction. Our findings suggest that proper color correction can significantly impact CAD system performance, and we recommend its application prior to quantitative texture analysis in gynaecological endoscopy. PMID- 17282961 TI - Reconstruction of computed tomography with metal implants. AB - Computed Tomograghy has played a key role in bone structure imaging for over two decades. However, when a metal implant present in the sample, the reconstructions are seriously distorted by artefacts, and no method has successfully met the clinical demands. This paper presents a new method for partial reconstruction in Computed Tomography. The metal implant is reconstructed separately and the correspondence is isolated from the projection. The boundary between the metal implants and other tissues are clearer. The method is demonstrated by experiments. PMID- 17282962 TI - Accelerating Monte Carlo image reconstruction of a PMMA phantom through variance reduction techniques for quality control in digital mammography. AB - Mammography is a non-invasive technique used for the detection of breast lesions. The use of this technique in a breast screening program requires a continuous quality control testing in mammography units for ensuring a minimum absorbed glandular dose without modifying image quality. Digital mammography has been progressively introduced in screening centers, since recent evolution of photostimulable phosphor detectors. The aim of this work is the validation of a methodology for reconstructing digital images of a polymethyl-methacrylate (PMMA) phantom (P01 model) under pure Monte Carlo techniques. A reference image has been acquired for this phantom under automatic exposure control (AEC) mode (28 kV and 14 mAs). Some variance reduction techniques (VRT) have been applied to improve the efficiency of the simulations, defined as the number of particles reaching the imaging system per starting particle. All images have been used and stored in DICOM format. The results prove that the signal-to-noise ratio (SNR) of the reconstructed images have been increased with the use of the VRT, showing similar values between different employed tallies. As a conclusion, these images could be used during quality control testing for showing any deviation of the exposition parameters from the desired reference level. PMID- 17282963 TI - Computer-assisted Sonographic Analysis of the Hepatorenal and Textural Features for the Diagnosis of the Fatty Liver. AB - We investigated the B-mode ultrasound (US) images of abdomen by normalizing the gray level values of the liver with the representative gray levels (RGL's) of the liver parenchyma, renal cortex, subcutaneous fat, to quantify the fatty infiltration of the liver (FIL). The RGL's were compared with the clinical diagnosis of the FIL showing good correlation between them. PMID- 17282964 TI - Transdifferentiation of bone marrow stem cells into acinar cells using a double chamber system. AB - BACKGROUND/PURPOSE: Hypofunction of the salivary glands can substantially affect quality of life. Current treatments for salivary hypofunction are of limited effectiveness. Although the implantation of functional salivary gland tissue from autologous glandular cells represents a possible physiologic solution to this problem, tissue engineering of salivary glands would require the generation of a great number of acinar cells (ACs). The purpose of this study was to investigate the feasibility of transdifferentiation of bone marrow stem cells (BMSCs) into functional ACs using a co-culture system. METHODS: BMSCs were isolated from adult rats and co-cultured with rat parotid ACs using a double chamber system. The transdifferentiation of BMSCs was evaluated by immunocytochemical analysis of alpha-amylase, which has unique functional expression in ACs. RESULTS: Expression of alpha-amylase, indicating successful transdifferentiation of BMSCs into ACs, was found in 30% of BMSCs after co-culturing for 1 week, and in 50% after co culturing for 2 and 3 weeks. CONCLUSION: This study has demonstrated the potential of rat BMSCs to transdifferentiate into ACs, and support the feasibility of application of BMSCs in salivary gland tissue engineering. PMID- 17282965 TI - Intrapulmonary bronchogenic cysts: computed tomography, clinical and histopathologic correlations. AB - BACKGROUND/PURPOSE: Bronchogenic cysts (BCs) are usually located in the mediastinum and they occur less commonly in the lung parenchyma. This study investigated the findings from computed tomography (CT) images, clinical presentation and histopathologic findings of intrapulmonary BCs. METHODS: From the last 7 years, the CT images of 20 patients (12 females, 8 males; mean age, 38.8 +/- 21.7 years; median age, 34 years) with intrapulmonary BC were available. Contrast-enhanced CT findings were characterized and correlated with clinical presentation and histopathologic findings (using Fisher's exact tests). RESULTS: The majority of intrapulmonary BCs were subpleural in location (55%), in the lower lobes (60%), symptomatic (80%), and in adults (90%). Three CT patterns were identified: cyst with content of fluid attenuation (9 patients), cyst with air and fluid content (9 patients), cyst with content of soft tissue attenuation (2 patients). Preoperative diagnosis of intrapulmonary BC was correct in only 20% using the CT criteria of cysts with fluid attenuation and without anomalous blood supply. Cysts with air component were significantly larger than those without air component (p = 0.0452), but cyst size and air component were not correlated with clinical presentation. Surrounding infiltration or thick wall on CT were significantly correlated with the presence of any clinical symptom (p = 0.014) or fever (p = 0.042). CT findings of surrounding consolidation, ground glass opacity or thick wall were significantly correlated with chronic inflammation or pneumonic change on histopathology (p = 0.0008). CONCLUSION: There is a wide spectrum of intrapulmonary BCs that have CT findings that are correlated with clinical presentations and histopathologic findings. PMID- 17282967 TI - Treatment outcome of pulmonary tuberculosis in eastern Taiwan - experience at a medical center. AB - BACKGROUND/PURPOSE: The World Health Organization (WHO) has proposed that treatment outcome is an important indicator of tuberculosis control. This study investigated the outcome of tuberculosis treatment at a medical center in eastern Taiwan. METHODS: A total of 166 pulmonary tuberculosis patients notified by Tzu Chi Hospital in 2002 were included in this study. Treatment outcome data were collected at the local level and categorized according to WHO recommendations as cured, treatment completed, failed, died, defaulted, or transferred. Outcomes of the 166 patients, as reported by the National Tuberculosis Program were obtained from the Taiwan Center for Disease Control (Taiwan CDC) for comparison. RESULTS: Of the 166 patients, outcome was classified as cured in 46 (27.7%), treatment completed in 73 (44.0%), died in 27 (16.3%), treatment failed in five (3.0%), and defaulted in 15 (9.0%). Males were more likely to die or to default than females, and the elderly were more likely to die than younger patients. Patients with comorbidities were significantly more likely to die than patients without (p = 0.025). Patients with a history of tuberculosis were more likely to default (p = 0.050). Smear-positive patients were more likely to fail, and patients without cavitation on chest radiograph were more likely to have successful treatment. Outcomes of 26 (15.7%) cases in this cohort were unavailable (18 cases) or inaccurate (8 cases) on the Taiwan CDC website. CONCLUSION: The unsatisfactory outcome of pulmonary tuberculosis treatment in this medical center in eastern Taiwan highlights the importance of implementing directly observed treatment short course strategy. Improvement in the quality of data reported by the National Tuberculosis Program is urgently needed. PMID- 17282966 TI - Detection of human metapneumovirus in hospitalized children with acute respiratory tract infection using real-time RT-PCR in a hospital in northern Taiwan. AB - BACKGROUND/PURPOSE: Human metapneumovirus (hMPV) is a newly discovered respiratory pathogen. This prospective hospital-based study investigated the clinical role and features of hMPV in Taiwan. METHODS: Respiratory specimens collected from hospitalized children with acute respiratory tract infection between September 1, 2003 and April 10, 2005 were screened for metapneumovirus using real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: During the study period, 930 specimens were obtained from 926 hospitalized children. After exclusion of 200 cases due to lack of clinical evidence of airway infection or diseases with known etiology, 726 were included in the analysis. Among these, 33 children had a positive result for hMPV infection. The majority of these patients were admitted during spring and early summer. Twenty-one (63.6%) were younger than 2 years of age. hMPV accounted for 13.3% of respiratory infections occurring between the ages of 18 and 24 months and was as common a respiratory pathogen as respiratory syncytial virus (RSV) in that age group. The 11 patients (33.3%) with underlying diseases had a similar disease course to those without underlying diseases. A co-pathogen was found in 11 patients (33.3%). Infected children between 2 and 5 years of age had significantly higher titers of hMPV in their respiratory specimens (103.88 copies/microL) than children younger than 2 years (102.26 copies/microL) (p = 0.013) and children older than 5 years (102.25 copies/microL) (p = 0.005). hMPV positive cases were significantly older than those with RSV infection (p = 0.002) and had a shorter duration of hospitalization (p = 0.001), fewer days of oxygen use (p = 0.001) and higher levels of C-reactive protein (p = 0.004). CONCLUSION: Metapneumovirus circulates in children in northern Taiwan during spring and early summer. hMPV was the most common respiratory pathogen in children aged between 18 and 24 months hospitalized with acute respiratory tract infection. Real-time RT PCR is a sensitive method for investigating the epidemiology and diseases associated with hMPV. PMID- 17282968 TI - Prevalence of intestinal infection due to Cryptosporidium species among Taiwanese patients with human immunodeficiency virus infection. AB - BACKGROUND/PURPOSE: Cryptosporidiosis causes significant morbidity and mortality in human immunodeficiency virus (HIV)-infected patients who do not receive highly active antiretroviral therapy. Related data on cryptosporidiosis in Taiwanese HIV infected patients are very limited. This study assessed the prevalence of intestinal infection due to Cryptosporidium spp. among Taiwanese patients with HIV infection. METHODS: This retrospective review included 1044 patients with HIV infection treated between June 1994 and June 2004. Intestinal colonization due to Cryptosporidium spp. was identified by polymerase chain reaction and restriction fragment length polymorphism of stool specimens collected from 332 of the HIV infected patients without gastrointestinal symptoms, 90% of whom were receiving highly active antiretroviral therapy. RESULTS: Five out of 1044 (0.5%) HIV infected patients had a diagnosis of intestinal cryptosporidiosis by endoscopic biopsy or examinations of stool specimens. Intestinal colonization due to Cryptosporidium spp. was found in four of 332 (1.2%) asymptomatic HIV-infected patients between 2001 and 2003; two were due to C. hominis, and one each were due to C. felis and C. meleagridis. CONCLUSION: Our findings indicate that the prevalence of intestinal colonization due to Cryptosporidium is low among HIV infected patients in Taiwan. PMID- 17282969 TI - Eosinophil apoptosis induced by fungal immunomodulatory peptide-fve via reducing IL-5alpha receptor. AB - BACKGROUND/PURPOSE: Eosinophils are important effector cells in the pathogenesis of allergic bronchial asthma. Enhancement of eosinophil apoptosis has been considered to have therapeutic effect on allergic disease. Fungal immunomodulatory peptide (FIP)-fve has been reported to possess immunoprophylactic activities for allergic diseases. The purpose of this study was to investigate the modulation of FIP-fve on human eosinophil survival derived from allergic asthmatic patients. METHODS: Eosinophils were obtained from allergic asthmatic patients and purified with the use of density gradients and immunomagnetic beads negative selection. Apoptosis was assessed by annexin V and propidium iodide. The apoptotic signal protein, CD95 and IL-5 receptor expression were assessed by Western blot and flow cytometric analysis. RESULTS: When the eosinophils were treated with FIP-fve in the presence of IL-5, IL-5-enhanced eosinophil survival diminished. FIP-fve could reduce IL-5-mediated survival of eosinophils and decrease IL-5Ralpha expression. In the presence of FIP-fve, CD95 expression was upregulated and Bcl-xL and pro-caspase 3 expression were downregulated in cultured eosinophils. CONCLUSION: The results suggest that FIP fve can inhibit IL-5-mediated survival of eosinophils through the modulation of cytokine receptor expression and apoptotic signal protein production. The modulatory effect of FIP-fve on eosinophil apoptosis in vitro indicates that it may have some therapeutic effect on eosinophil-related allergic inflammation in vivo. PMID- 17282971 TI - Porous polyethylene implants in orbital floor reconstruction. AB - BACKGROUND/PURPOSE: Various alloplastic materials are used in orbital wall reconstruction. This study investigated the outcome of patients treated with porous polyethylene sheet implants in the reconstruction of orbital floor fracture. METHODS: Twenty-one patients who underwent orbital reconstructions using 0.85-mm porous polyethylene sheets for the repair of orbital floor fracture were included. A transconjunctival approach was used in all patients. The mean duration of postoperative follow-up was 29.7 +/- 12.3 months. Postoperatively, results and complications such as infection and implant extrusion were followed up on the first day, the first week, monthly for the first 3 months and then every 3-6 months thereafter. RESULTS: All 21 patients had symptomatic diplopia before surgery. The diplopia resolved in 14 patients and improved in seven patients within the first month after surgery. All patients except one were free from diplopia at follow-up periods exceeding 6 months. Preoperative enophthalmos resolved in four of seven patients and improved in three. None of the patients developed orbital infection, implant exposure or migration, worsening diplopia, infraorbital anesthesia or loss of vision during follow-up. CONCLUSION: The study demonstrated that porous polyethylene implants in the repair of orbital wall fractures had good results with few complications. PMID- 17282970 TI - Radio-guided sentinel lymph node biopsy using periareolar injection technique for patients with early breast cancer. AB - BACKGROUND/PURPOSE: Sentinel lymph node (LN) biopsy has been widely adopted in the axillary staging of clinical node-negative breast cancer patients. This study aimed to evaluate the accuracy of radio-guided sentinel LN (SLN) biopsy (SLNB) using the periareolar injection technique for predicting the histopathologic status of axillary LNs in early breast cancer patients. METHODS: Between November 2003 and November 2004 in the National Taiwan University Hospital, radio-guided SLNB using the periareolar injection technique was consecutively performed in 213 female patients with early breast cancer (stage T1 and T2) but without clinically palpable axillary LN and previous chemotherapy. Two mCi of filtered (0.22 microm) (99m)Tc-sulfur colloid were injected in the afternoon 1 day before surgery (2-day protocol) or 1 mCi of the same radiopharmaceutical was injected on the morning of the surgery (1-day protocol). During surgery, a handheld gamma probe was used to identify the LNs with radioactivity in the axilla. A node was deemed a SLN if its radioactivity was >10% of the hottest node. All the SLNs identified were removed for histology. RESULTS: Radioactive SLN was identified at surgery in 207 patients. The SLN identification rate was 97.2% (207/213). Of these 207 patients, 163 patients had received both SLNB and axillary LN dissection. Among these 163 patients, 77 patients had LN metastases and four had negative SLN but positive non-SLN. The false-negative rate of SLNB for the detection of axillary LN metastases was 5.2% (4/77). There were no statistical differences between false negative and SLN positive groups for all factors. CONCLUSION: Our study suggests that SLNB with periareolar injection of radiocolloid provides valuable information on the axillary nodal status in patients with early breast cancer. PMID- 17282972 TI - Applying a multiple screening program aided by a guideline-driven computerized decision support system - a pilot experience in Yun-Lin, Taiwan. AB - BACKGROUND/PURPOSE: Although preventive tools decrease morbidity and mortality and promote health, these services are often underutilized. The purpose of this study was to create a workflow for an outpatient setting that incorporated a computerized decision support system to implement preventive recommendations as well as to evaluate its impacts on facilitating preventive care. METHODS: Subjects visiting National Taiwan University Hospital Yun-Lin Branch were evaluated by a questionnaire, which contained items to trigger production rules to check the eligibility of screening for high coronary risk, diabetes mellitus, lipid disorder, hypertension, obesity, tobacco use, depression, colorectal cancer, breast cancer, cervical cancer, and osteoporosis. Patients were given health information about the diseases they were at risk for and the merits of preventive measures, scheduled for a clinic visit, and arranged to have access to screening tools. Physicians were prompted with clinical reminders on the encounter. The over-all effectiveness of 11 components in this screening program was evaluated in terms of expected life saving. The cost-effectiveness ratio was represented in US dollars per life-year saved. RESULTS: A total of 283 men and 199 women were identified to need one to six preventive interventions during a 2 month period. Preventive consultation was arranged and screening tools were performed. It was estimated that 412-1014 subjects would be needed to attend the program so as to save one life. The cost-effectiveness ratio ranged from 30,000 US dollars to 40,000 US dollars per life-year saved. CONCLUSION: A computer-aided screening program driven by the US Preventive Services Task Force recommendations has been successfully implemented in Yun-Lin, Taiwan, and provided useful information about local epidemiology and implications for future health policy making. PMID- 17282973 TI - Congenital central hypoventilation syndrome with PHOX2B gene mutation in a Taiwanese infant. AB - Congenital central hypoventilation syndrome (CCHS) is a rare disease that is characterized by failure in the autonomic control of breathing. Recent reports have identified mutation of the paired mesoderm homeobox protein 2b (PHOX2B) gene as playing a major role in CCHS. Increasing polyalanine repeat number is associated with a more severe clinical phenotype. We report a newborn male infant with the clinical manifestations of apnea and cyanosis requiring immediate endotracheal intubation at the age of 1 day. Recurrent hypoventilation with hypercapnia and hypoxemia occurred during sleep after weaning from the ventilator. No primary cardiopulmonary disease was identified. These clinical manifestations are compatible with CCHS. PHOX2B gene mutation analysis performed at the age of 4 months revealed expanded alleles containing polyalanine 26 repeats, further supporting the diagnosis of CCHS. Continuous ventilator support was necessary and tracheostomy was ultimately performed at the age of 5 months due to ventilator dependence. He was discharged with home ventilator support at the age of 6 months. PMID- 17282974 TI - Emphysematous prostatitis caused by Klebsiella pneumoniae. AB - Emphysematous prostatitis is a rare condition that is characterized by gas and abscess accumulation in the prostate. We report a 60-year-old man with emphysematous prostatitis caused by Klebsiella pneumoniae. He had a history of recently diagnosed diabetes mellitus and a 16-year history of alcoholic liver cirrhosis. He was admitted due to fever, dysuria and difficult urination. Physical examination revealed lower abdominal tenderness and prostatic fluctuance on digital examination. Leukocytosis, pyuria and elevated C-reactive protein were found. Abdominal radiography disclosed a collection of abnormal air pockets in the lower pelvic cavity and computed tomography scans corroborated the existence of extensive air collection in the prostate. Under the impression of emphysematous prostatitis, the patient was successfully treated with transurethral incision of the prostate and antibiotics for 6 weeks; there were no urinary sequelae during 6 months of follow-up. PMID- 17282975 TI - Embryonic biliary atresia in a very-low-birth-weight premature infant. AB - Two major forms of biliary atresia, the embryonic and perinatal type, are considered to have different pathogeneses and distinct prognoses. Embryonic biliary atresia is associated with worse prognosis. We report a case of embryonic biliary atresia in a preterm male infant of 31 weeks of gestation and weighing 1375 g, with the initial manifestation of intermittent acholic stool 5 days after birth. Kasai portoenterostomy was per-formed at the age of 51 days when he weighed 2164 g. Nevertheless, poorly restored bile flow and progressive cholestasis led to early liver transplantation at the age of 8 months. Liver function had recovered to normal levels by the age of 12 months. Diagnosis of biliary atresia in preterm infants is difficult and requires a high index of suspicion and careful workup. This case illustrates the poor outcome of embryonic biliary atresia and that early liver transplantation may be necessary to improve the prognosis. PMID- 17282976 TI - Pulmonary tuberculosis with delayed tuberculosis infection of total knee arthroplasty. AB - Tuberculous prosthetic joint infection is rare. While early diagnosis is critical for treatment, it is usually delayed. Here, we present the case of a 72-year-old patient who underwent total knee arthroplasty for his right knee due to degenerative arthritis 4 years ago. Three years after arthroplasty, pulmonary tuberculosis was found and he hesitated on starting antituberculosis chemotherapy. He suffered from progressive pain and swelling of the right prosthetic knee for 2 months before this admission. The pathologic report of the debridement of the right prosthetic knee was caseous granulomatous inflammation with positive acid-fast staining bacilli. The culture of the debridement also yielded Mycobacterium tuberculosis. He died due to aspiration pneumonia with multiorgan dysfunction. This case is a reminder of the possibility of tuberculosis while dealing with prosthetic joint infection. PMID- 17282977 TI - Mutation analyses of COL7A1 gene in three Taiwanese patients with severe recessive dystrophic epidermolysis bullosa. AB - Dystrophic epidermolysis bullosa (DEB) is a hereditary mechanobullous disorder characterized by fragility of the skin and mucous membranes caused by abnormal anchoring fibrils. Both dominant and recessive DEB are caused by mutations in COL7A1, the gene encoding type VII collagen, the major component of anchoring fibrils. We performed mutation analysis of COL7A1 in three patients with recessive DEB. The diagnosis of DEB was based on the characteristic clinical features and confirmed histopathologically. All 118 exons and flanking intron boundaries of COL7A1 were amplified. Four novel mutations (3373insGG, 7769delG, E1535X, G2061E) and two potential splicing mutations were detected. The first three of these mutations resulted in premature termination codons, while G2061E caused a glycine substitution mutation in the triple-helical domain. This is the first report of mutation analyses of the COL7A1 gene in Taiwanese pedigrees with recessive DEB. Each patient had a heterozygous premature termination codon mutation combined with either a glycine substitution mutation in the critical triple-helical collagenous domain or a potential splicing mutation. These genotypes correlate well with the severe clinical phenotype of recessive DEB. PMID- 17282978 TI - Complications of intraoperative transesophageal echocardiography in adult cardiac surgical patients - experience of two institutions in Taiwan. AB - There is some safety concern about transesophageal echocardiography (TEE) when it is used routinely during cardiac operations. The purpose of this investigation was to study the incidence of intraoperative TEE-associated complications in adult cardiac surgical patients. The study population comprised 6255 consecutive adult cardiac surgical patients with intraoperative TEE examinations. TEE associated complications occurred in 25 patients (0.4%). Most of these complications consisted of oropharyngeal mucosal bleeding (15/25, 60%). Esophageal perforation occurred in one patient. Two patients experienced upper gastrointestinal bleeding. Seven patients experienced dental injuries, and TEE probe insertion failed in 10 patients. We conclude that intraoperative TEE associated complications in cardiac operations is very low; the complication rate we found was comparable to previously reported values. PMID- 17282979 TI - Changes in gingival crevicular fluid interleukin-4 and interferon-gamma in patients with chronic periodontitis before and after periodontal initial therapy. AB - Cytokines are pivotal to the immune response of chronic periodontitis. The present study investigated the changes of gingival crevicular fluid (GCF) interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in patients with chronic periodontitis before and after initial nonsurgical periodontal therapy (NSPT). GCF was collected from 17 patients by means of Periopaper at baseline and 1 month after NSPT. IL-4 and IFN-gamma were measured by enzyme-linked immunoabsorbent assay. NSPT resulted in decreased total amount of IFN-gamma, increased concentration of IL-4, and increased ratio of IL-4 to IFN-gamma levels. We suggest that a low ratio of IL-4 to IFN-gamma levels might be involved in the destruction (diseased sites) of periodontal tissue, whereas an increased ratio of IL-4 to IFN-gamma levels could be related to the improvement of clinical periodontal health. PMID- 17282980 TI - Predictive risk factors for upper gastrointestinal bleeding with simultaneous myocardial injury. AB - The aims of this study were to: (1) evaluate the epidemiology of simultaneous upper gastrointestinal bleeding (UGIB) and myocardial injury using parameters including troponin I (TnI); and (2) investigate the predictive risk factors of this syndrome. One hundred and fifty-five patients (101 men, 54 women; mean age, 64.7+/-10.4 years; range, 38-94 years) at the emergency department (ED) with the major diagnosis of UGIB were included. They underwent serial electrocardiography (ECG) and cardiac enzyme follow-up. Emergent gastroendoscopy was performed within 24 hours in most patients except for those who refused or were contraindicated. Mild myocardial injury was defined as the presence of any of the following: typical ST-T change on ECG, elevated creatine kinase-MB (CK-MB)>12 U/L, or TnI>0.2 ng/dL. Moderate myocardial injury was defined as the presence of any two of the previously mentioned conditions. In total, 51 (32.9%) and 12 (7.74%) patients developed mild and moderate myocardial injuries, respectively. Myocardial injury was more common among patients with variceal bleeding (20/25=80.0%) than those with ulcer bleeding (23/112=20.5%). It could partially be attributed to a higher baseline TnI level in cirrhotic patients. After adjusting for significant risk factors revealed by the univariate analysis, UGIB patients with a history of liver cirrhosis and more than three cardiac risk factors comprised a high-risk group for simultaneously developing myocardial injury. Other factors including age, gender, the color of nasogastric tube irrigation fluid, history of nonsteroidal anti-inflammatory drug use, vasopressin or terlipressin administration, vital signs, and creatinine recorded at the ED were not significant predictors. Those who developed myocardial injury had a longer hospital stay (mean duration, 8.73+/-6.94 vs. 6.34+/-2.66 days; p=0.03) and required transfusion of more units of packed erythrocytes. PMID- 17282981 TI - Cost-effectiveness of elderly health examination program: the example of hypertension screening. AB - The National Health Insurance (NHI) and social welfare agencies have implemented the Elderly Health Examination Program (EHEP) for years. No study has ever attempted to evaluate whether this program is cost-effective. The purposes of this study were, firstly, to understand the prevalence and incidence rates of hypertension and, secondly, to estimate the cost and effectiveness of the EHEP, focusing on hypertension screening. The data sources were: (1) hypertension and clinical information derived from the 1996 and 1997 EHEP, which was used to generate prevalence and incidence rates of hypertension; and (2) claim data of the NHI that included treatment costs of stroke patients (in- and outpatients). Hypothetical models were used to evaluate the cost-effectiveness of the hypertension screening program in various conditions. Sensitivity analysis was also employed to evaluate the effect of each estimation indicator on the cost and effectiveness of the hypertension screening program. A total of 28.3% of the elderly population in Kaohsiung (25,174 of 88,812) participated in the 1996 EHEP; 14,915 of them participated in the following 1997 EHEP, with a retention rate of 59.3%. Criteria from the Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) (systolic blood pressure/diastolic blood pressure>or=160/95 mmHg or taking antihypertensive drugs) were used; we found that prevalence and incidence rates of hypertension were 24.6% and 6.6%, respectively. Hypertension rates are increasing in the aging process as shown in both prevalence and incidence models. In comparison with non participants, the prevalence model indicates that each hypertension patient who had attended the EHEP not only saved NT$34,570-34,890 in medical and associated costs, but also increased their lifespan by 128 days. The present findings suggest that the EHEP is a cost-effective program with health and social welfare policy implications. With the relatively low participation rate of the EHEP, health and social agencies need to put more effort into the promotion of this free health examination program to attract potential participants. In doing so, the population at risk for hypertension would be identified for early treatment, and the probability of having stroke could be decreased. Consequently, health care expenditures for treatment and caregiving of stroke patients would be minimized. Finally, it should be noted that the sensitivity and values of selected parameters can modify the results of cost-effectiveness analysis. Interpretations of the effects of prevention services on costs and effectiveness need to be treated with caution. PMID- 17282982 TI - Corneal flap thickness during laser in situ keratomileusis. AB - To analyze the actual corneal flap thickness (FT) after flap making by MK-2000 microkeratome during laser in situ keratomileusis (LASIK), 42 females and 20 males with myopia or myopic astigmatism were enrolled in this study. FTs were created using a microkeratome with a 130 microm head. Corneal thickness was measured by ultrasonic pachymeter. The correlations between FT and central corneal thickness (CCT), keratometric power and age were analyzed. The mean age at operation for all study subjects was 27.6+/-4.9 years. The average FT was 133.2+/-15.4 microm. The average CCT was 540.+/-30.3 microm. The average keratometric power was 43.66+/-1.32 D. There was a positive correlation between FT and CCT and no correlation between FT and keratometric power or between FT and age. We recommend that LASIK surgeons inspect the actual FT when using microkeratome. PMID- 17282983 TI - Easy category for complex congenital cardiac segmental connections. AB - To clarify the variant complex congenital cardiac defects, Van Praagh introduced a system of segmental sets to classify the majority of congenital heart diseases, but the code system entails some confusion for complete understanding. We attempted to recategorize the variant sets into four subgroups according to the connection of the atrial-ventricular and ventricular-arterial segments. This complexity can simply be grouped into four subgroups with regularities. From a simple table so formed, we can quickly ascertain the hemodynamics and the circulatory physiology, and therefore quickly determine the treatment protocol for variant complex hearts. PMID- 17282984 TI - Brain abscess in adult cirrhotic patients: two case reports. AB - Patients who have liver cirrhosis are at increased risk of bacterial infections, such as bacteremia, meningitis, pneumonia, urinary tract infections, and spontaneous bacterial peritonitis, due to immunodeficiency associated with the severity of the cirrhosis. Although bacterial infections are frequent in cirrhotic patients, only isolated cases of brain abscess have been reported. In these cirrhotic patients, the initial presentation of brain abscess may not be fever or leukocytosis, but focal neurologic deficits. In addition, for consideration of blood-brain barrier penetration, the anti-biotic choice postoperatively is also quite different from other infections outside the central nervous system. We will discuss two cases of brain abscess in cirrhotic patients with special emphasis on the clinical presentation, magnetic resonance spectroscopic findings, organism encountered, therapeutic strategy, and prognosis. PMID- 17282985 TI - Infective endocarditis with uveitis: a rare case report. AB - We report a case of a 51-year-old diabetic male who presented with a complaint of intermittent chills and fever that he had experienced for 10 days. No obvious respiratory tract, genitourinary tract, gastrointestinal tract, or skin lesions were observed. Blood culture data were positive for group B beta-streptococcus. Transthoracic and transesophageal echocardiography revealed vegetation in the anterior leaflet of the mitral valve. The patient was diagnosed with infective endocarditis (IE) and prescribed a parenteral antibiotic. Three days after admission, the patient complained of progressively blurred vision. Slit lamp examination found fine keratic precipitates and aqueous cells in the anterior chambers in both eyes, implying that the patient had uveitis. He was then prescribed a topical steroid for 4 months, and his vision improved gradually. This case is an important reminder that uveitis, not only endophthalmitis, can occur with IE. Treatment for one condition, if misapplied, may worsen the other. PMID- 17282986 TI - Painless aortic dissection with initial symptom of right upper extremity weakness: a case report. AB - Thoracic aortic dissection is a dangerous disease. It usually presents as severe chest or back pain. Symptoms resulting from aortic branch involvement may also be involved. Sometimes, it presents with atypical symptoms. Here, we report a patient who came to the emergency department (ED) because of acute onset of right upper limb weakness and numbness. Brain computed tomography (CT) was performed initially because cerebral vascular disease was suspected. Subsequently, angiography was performed as artery occlusion of the limb was found. The patient suddenly collapsed in the ED. Stanford type A acute aortic dissection was found by chest CT. PMID- 17282987 TI - Introduction: energy for a sustainable future. PMID- 17282989 TI - Myelin repair: the role of stem and precursor cells in multiple sclerosis. AB - Multiple sclerosis is the most common potential cause of neurological disability in young adults. The disease has two distinct clinical phases, each reflecting a dominant role for separate pathological processes: inflammation drives activity during the relapsing-remitting stage and axon degeneration represents the principal substrate of progressive disability. Recent advances in disease modifying treatments target only the inflammatory process. They are ineffective in the progressive stage, leaving the science of disease progression unsolved. Here, the requirement is for strategies that promote remyelination and prevent axonal loss. Pathological and experimental studies suggest that these processes are tightly linked, and that remyelination or myelin repair will both restore structure and protect axons. This review considers the basic and clinical biology of remyelination and the potential contribution of stem and precursor cells to enhance and supplement spontaneous remyelination. PMID- 17282991 TI - Regulatory pathways linking progenitor patterning, cell fates and neurogenesis in the ventral neural tube. AB - The assembly of neural circuits in the vertebrate central nervous system depends on the organized generation of specific neuronal subtypes. Studies over recent years have begun to reveal the principles and elucidate some of the detailed mechanisms that underlie these processes. In general, exposure to different types and concentrations of signals directs neural progenitor populations to generate specific subtypes of neurons. These signals function by regulating the expression of intrinsic determinants, notably transcription factors, which specify the fate of cells as they differentiate into neurons. In this review, we illustrate these concepts by focusing on the generation of neurons in ventral regions of the spinal cord, where detailed knowledge of the mechanisms that regulate cell identity has provided insight into the development of a number of neuronal subtypes, including motor neurons. A greater knowledge of the molecular control of neural development is likely to have practical benefits in understanding the causes and consequences of neurological diseases. Moreover, recent studies have demonstrated how an understanding of normal neural development can be applied to direct differentiation of stem cells in vitro to specific neuronal subtypes. This type of rational manipulation of stem cells may represent the first step in the development of treatments based on therapeutic replacement of diseased or damaged nervous tissue. PMID- 17282988 TI - Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain. AB - Post-embryonic neurogenesis is a fundamental feature of the vertebrate brain. However, the level of adult neurogenesis decreases significantly with phylogeny. In the first part of this review, a comparative analysis of adult neurogenesis and its putative roles in vertebrates are discussed. Adult neurogenesis in mammals is restricted to two telencephalic constitutively active zones. On the contrary, non-mammalian vertebrates display a considerable amount of adult neurogenesis in many brain regions. The phylogenetic differences in adult neurogenesis are poorly understood. However, a common feature of vertebrates (fish, amphibians and reptiles) that display a widespread adult neurogenesis is the substantial post-embryonic brain growth in contrast to birds and mammals. It is probable that the adult neurogenesis in fish, frogs and reptiles is related to the coordinated growth of sensory systems and corresponding sensory brain regions. Likewise, neurons are substantially added to the olfactory bulb in smell oriented mammals in contrast to more visually oriented primates and songbirds, where much fewer neurons are added to the olfactory bulb. The second part of this review focuses on the differences in brain plasticity and regeneration in vertebrates. Interestingly, several recent studies show that neurogenesis is suppressed in the adult mammalian brain. In mammals, neurogenesis can be induced in the constitutively neurogenic brain regions as well as ectopically in response to injury, disease or experimental manipulations. Furthermore, multipotent progenitor cells can be isolated and differentiated in vitro from several otherwise silent regions of the mammalian brain. This indicates that the potential to recruit or generate neurons in non-neurogenic brain areas is not completely lost in mammals. The level of adult neurogenesis in vertebrates correlates with the capacity to regenerate injury, for example fish and amphibians exhibit the most widespread adult neurogenesis and also the greatest capacity to regenerate central nervous system injuries. Studying these phenomena in non-mammalian vertebrates may greatly increase our understanding of the mechanisms underlying regeneration and adult neurogenesis. Understanding mechanisms that regulate endogenous proliferation and neurogenic permissiveness in the adult brain is of great significance in therapeutical approaches for brain injury and disease. PMID- 17282990 TI - Multipotent skin-derived precursors: adult neural crest-related precursors with therapeutic potential. AB - We previously made the surprising finding that cultures of multipotent precursors can be grown from the dermis of neonatal and adult mammalian skin. These skin derived precursors (SKPs) display multi-lineage differentiation potential, producing both neural and mesodermal progeny in vitro, and are an apparently novel precursor cell type that is distinct from other known precursors within the skin. In this review, we begin by placing these findings within the context of the rapidly evolving stem cell field. We then describe our recent efforts focused on understanding the developmental biology of SKPs, discussing the idea that SKPs are neural crest-related precursors that (i) migrate into the skin during embryogenesis, (ii) persist within a specific dermal niche, and (iii) play a key role in the normal physiology, and potentially pathology, of the skin. We conclude by highlighting some of the therapeutic implications and unresolved questions raised by these studies. PMID- 17282993 TI - Evaluation of neural plasticity in adult stem cells. AB - The role of stem cells has long been known in reproductive organs and various tissues including the haematopoietic system and skin. During the last decade, stem cells have also been identified in other organs, including the nervous system, both during development and in post-natal life. More recently, evidence has been presented that stem cells thought to be responsible for the generation of mature differentiated cells of one organ, such as haematopoietic stem cells, may have the ability to also differentiate across lineages and contribute to tissues other than haematopoietic cells, including neuronal tissue, suggesting that easily accessible stem cells sources may one day be useful in the therapy of ischaemic (stroke) and also degenerative diseases of the nervous system. Here, we will evaluate the validity of such claims based on a number of criteria we believe need to be fulfilled to definitively conclude that certain stem cells can give rise to functional neural cells that might be suitable for therapy of neural disorders. PMID- 17282994 TI - Introduction: stem cells and brain repair. PMID- 17282992 TI - Specification of CNS glia from neural stem cells in the embryonic neuroepithelium. AB - All the neurons and glial cells of the central nervous system are generated from the neuroepithelial cells in the walls of the embryonic neural tube, the 'embryonic neural stem cells'. The stem cells seem to be equivalent to the so called 'radial glial cells', which for many years had been regarded as a specialized type of glial cell. These radial cells generate different classes of neurons in a position-dependent manner. They then switch to producing glial cells (oligodendrocytes and astrocytes). It is not known what drives the neuron-glial switch, although downregulation of pro-neural basic helix-loop-helix transcription factors is one important step. This drives the stem cells from a neurogenic towards a gliogenic mode. The stem cells then choose between developing as oligodendrocytes or astrocytes, of which there might be intrinsically different subclasses. This review focuses on the different extracellular signals and intracellular responses that influence glial generation and the choice between oligodendrocyte and astrocyte fates. PMID- 17282996 TI - Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. AB - Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that typically affects optic nerves and spinal cord. Its pathogenic relationship to multiple sclerosis (MS) is uncertain. Unlike MS, NMO lesions are characterized by deposits of IgG and IgM co-localizing with products of complement activation in a vasculocentric pattern around thickened hyalinized blood vessels, suggesting a pathogenic role for humoral immunity targeting an antigen in the perivascular space. A recently identified specific serum autoantibody biomarker, NMO-IgG, targets aquaporin-4 (AQP4), the most abundant water channel protein in the CNS, which is highly concentrated in astrocytic foot processes. We analysed and compared patterns of AQP4 immunoreactivity in CNS tissues of nine patients with NMO, 13 with MS, nine with infarcts and five normal controls. In normal brain, optic nerve and spinal cord, the distribution of AQP4 expression resembles the vasculocentric pattern of immune complex deposition observed in NMO lesions. In contrast to MS lesions, which exhibit stage-dependent loss of AQP4, all NMO lesions demonstrate a striking loss of AQP4 regardless of the stage of demyelinating activity, extent of tissue necrosis, or site of CNS involvement. We identified a novel NMO lesion in the spinal cord and medullary tegmentum extending into the area postrema, characterized by AQP4 loss in foci that were inflammatory and oedematous, but neither demyelinated nor necrotic. Foci of AQP4 loss coincided with sites of intense vasculocentric immune complex deposition. These findings strongly support a role for a complement activating AQP4-specific autoantibody as the initiator of the NMO lesion, and further distinguish NMO from MS. PMID- 17282995 TI - Relationship of height, weight and body mass index to the risk of hip and knee replacements in middle-aged women. AB - OBJECTIVES: To examine the effect of height, weight and body mass index (BMI) on the risk of hip and knee replacement in middle-aged women. METHODS: In a prospective cohort study 490 532 women aged 50-69 yrs who were recruited in the UK in 1996-2001 were followed over 2.9 yrs for incident primary hip and knee replacements. RESULTS: Height, weight and BMI were all associated with the risk of hip and knee replacement. Comparing the tallest group (>or=170 cm) with the shortest (<155 cm) the relative risks were 1.90 (95%CI 1.55-2.32) for hip replacement and 1.55 (95%CI 1.19-2.00) for knee replacement. Comparing the heaviest group (>or=75 kg) with the lightest (<60 kg) the relative risks of hip and knee replacement were 2.37 (95%CI 2.04-2.75) and 9.71 (95%CI 7.39-12.77), respectively. Comparing obese women (BMI >or= 30 kg/m(2)) to women with a BMI < 22.5 kg/m(2), the relative risks for hip and knee replacement were 2.47 (95%CI 2.11-2.89) and 10.51 (95%CI 7.85-14.08), respectively. These effects did not vary according to age, education, alcohol and tobacco consumption, or with use of hormonal therapies. Currently, an estimated 27% of hip replacements and 69% of knee replacements in middle-aged women in the UK are attributable to obesity. CONCLUSION: In middle-aged women, the risk of having a hip or knee replacement increases with both increasing height and increasing BMI. From a clinical perspective, relatively small increases in average BMI among middle-aged women are likely to have a substantial impact on the already increasing rates of joint replacement in the UK. PMID- 17282998 TI - NetPhosYeast: prediction of protein phosphorylation sites in yeast. AB - We here present a neural network-based method for the prediction of protein phosphorylation sites in yeast--an important model organism for basic research. Existing protein phosphorylation site predictors are primarily based on mammalian data and show reduced sensitivity on yeast phosphorylation sites compared to those in humans, suggesting the need for an yeast-specific phosphorylation site predictor. NetPhosYeast achieves a correlation coefficient close to 0.75 with a sensitivity of 0.84 and specificity of 0.90 and outperforms existing predictors in the identification of phosphorylation sites in yeast. AVAILABILITY: The NetPhosYeast prediction service is available as a public web server at http://www.cbs.dtu.dk/services/NetPhosYeast/. PMID- 17282999 TI - Assessment of the probabilities for evolutionary structural changes in protein folds. AB - MOTIVATION: The evolution of protein sequences can be described by a stepwise process, where each step involves changes of a few amino acids. In a similar manner, the evolution of protein folds can be at least partially described by an analogous process, where each step involves comparatively simple changes affecting few secondary structure elements. A number of such evolution steps, justified by biologically confirmed examples, have previously been proposed by other researchers. However, unlike the situation with sequences, as far as we know there have been no attempts to estimate the comparative probabilities for different kinds of such structural changes. RESULTS: We have tried to assess the comparative probabilities for a number of known structural changes, and to relate the probabilities of such changes with the distance between protein sequences. We have formalized these structural changes using a topological representation of structures (TOPS), and have developed an algorithm for measuring structural distances that involve few evolutionary steps. The probabilities of structural changes then were estimated on the basis of all-against-all comparisons of the sequence and structure of protein domains from the CATH-95 representative set. The results obtained are reasonably consistent for a number of different data subsets and permit the identification of several 'most popular' types of evolutionary changes in protein structure. The results also suggest that alterations in protein structure are more likely to occur when the sequence similarity is >10% (the average similarity being approximately 6% for the data sets employed in this study), and that the distribution of probabilities of structural changes is fairly uniform within the interval of 15-50% sequence similarity. AVAILABILITY: The algorithms have been implemented on the Windows operating system in C++ and using the Borland Visual Component Library. The source code is available on request from the first author. The data sets used for this study (representative sets of protein domains, matrices of sequence similarities and structural distances) are available on http://bioinf.mii.lu.lv/epsrc_project/struct_ev.html. PMID- 17282997 TI - The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene. AB - Rapid-onset dystonia-parkinsonism (RDP) (also known as DYT12) is characterized by the abrupt onset of dystonia and parkinsonism and is caused by mutations in the ATP1A3 gene. We obtained clinical data and sequenced the ATP1A3 gene in 49 subjects from 21 families referred with 'possible' RDP, and performed a genotype phenotype analysis. Of the new families referred for study only 3 of 14 families (21%) demonstrated a mutation in the ATP1A3 gene, but no new mutations were identified beyond our earlier report of 6. Adding these to previously reported families, we found mutations in 36 individuals from 10 families including 4 de novo mutations and excluded mutations in 13 individuals from 11 families. The phenotype in mutation positive patients included abrupt onset of dystonia with features of parkinsonism, a rostrocaudal gradient, and prominent bulbar findings. Other features found in some mutation carriers included common reports of triggers, minimal or no tremor at onset, occasional mild limb dystonia before the primary onset, lack of response to dopaminergic medications, rare abrupt worsening of symptoms later in life, stabilization of symptoms within a month and minimal improvement overall. In comparing ATP1A3 mutation positive and negative patients, we found that tremor at onset of symptoms, a reversed rostrocaudal gradient, and significant limb pain exclude a diagnosis of RDP. A positive family history is not required. Genetic testing for the ATP1A3 gene is recommended when abrupt onset, rostrocaudal gradient and prominent bulbar findings are present. PMID- 17283000 TI - Trends and contexts in European cardiology practice for the next 15 years: the Madrid Declaration: a report from the European Conference on the Future of Cardiology, Madrid, 2-3 June 2006. AB - In the near future, the practice of cardiology in Europe will be strongly influenced by a complex interplay of epidemiological, social, economical, professional, and technological evolving factors. The present report summarizes the conclusions of an expert conference organized by the European Society of Cardiology to discuss the interactions between these phenomena, in an attempt to foresee the potential scenario in which cardiovascular healthcare and research will develop in the near future, and to anticipate solutions to the identified problems. PMID- 17283001 TI - Levosimendan: perpetuum mobile? PMID- 17283002 TI - Biventricular non-compaction and giant left atrial appendage. PMID- 17283003 TI - Role of the implantable defibrillator among elderly patients with a history of life-threatening ventricular arrhythmias. AB - AIMS: The implantable defibrillator (ICD) reduces arrhythmic and all-cause mortality in patients with a history of life-threatening ventricular arrhythmias. However, its effectiveness in elderly patients is uncertain, given their competing risk of non-arrhythmic death. METHODS AND RESULTS: Individual patient data from all three secondary prevention trials comparing the ICD to amiodarone were pooled. Patients were divided into two groups based on age < 75 and > or = 75 years. Patient characteristics were reported and the effect of the ICD on all cause mortality and arrhythmic death was determined for each group. The effect of age on these outcomes was determined by evaluating the interaction term (age treatment). A total of 1866 patients were included in this analysis. Their mean age was 63.7 +/- 10.4 years (intra-quartile range 58-71 years). There were 252 patients > or = 75 years old (13.5% of total). Patients > or = 75 years old had a similar left ventricular (LV) ejection fraction (EF)(32.6 +/- 13.7 vs. 33.8 +/- 14.9%, P = 0.20) and baseline prevalence of NYHA class 3 or 4 heart (12.3 vs. 11.8%, P = 0.38) failure as younger patients, but were less likely to have ventricular fibrillation as their presenting arrhythmia (39 vs. 53%, P = 0.0001). Over a mean follow-up of 2.3 years, older patients were more likely to die of non arrhythmic death (8.74% per year vs. 3.96% per year, P = 0.001) and arrhythmic death (6.73% per year vs. 3.84% per year, P = 0.03). The ICD significantly reduced all-cause and arrhythmic death in patients < 75 years old (all-cause death HR = 0.69, 95% CI: 0.56-0.85, P < 0.0001; arrhythmic death HR = 0.44, 95% CI: 0.32-0.62, P < 0.0001), but not in patients > or = 75 years old (all-cause death HR = 1.06, 95% CI: 0.69-1.64, P = 0.79; arrhythmic death HR = 0.90, 95% CI: 0.42-1.95, P = 0.79). The interaction between age > or = 75 and ICD use was of borderline significance in each case (P = 0.09 and P = 0.11, respectively). CONCLUSION: Elderly patients with a history of life-threatening ventricular arrhythmias have a high incidence of non-arrhythmic death. In these patients, the ICD may not afford the same survival advantage over amiodarone that is seen in younger patients. ICD therapy should not be withheld based on age alone; however, physicians should carefully consider the risk of non-arrhythmic death among elderly patients when selecting the appropriate therapy for an individual. PMID- 17283004 TI - Unruptured congenital aneurisms of the right and left sinuses of Valsalva. PMID- 17283005 TI - Trendelenburg position with hip flexion as a rescue strategy to increase spinal anaesthetic level after spinal block. AB - BACKGROUND: When the level achieved by a spinal anaesthetic is too low to perform surgery, patients are usually placed in the Trendelenburg position. However, cephalad spread of the hyperbaric spinal anaesthetics may be limited by the lumbar lordosis. The Trendelenburg position with the lumbar lordosis flattened by hip flexion was evaluated as a method to extend the analgesic level after the administration of hyperbaric local anaesthetic. METHODS: When the pinprick block level was lower than T10 5 min after intrathecal injection of hyperbaric bupivacaine (13 mg), patients were recruited to the study and randomly allocated to one of the two positions: the Trendelenburg position with hip flexion (hip flexion group, n = 20) and the Trendelenburg position without hip flexion (control group, n = 20). Each assigned position was maintained for 5 min and then patients were returned to the horizontal supine position. Spinal block level was assessed by pinprick, cold sensation, and modified Bromage scale at intervals for the following 150 min. RESULTS: The maximum level of pinprick and cold sensory block [median (range)] was higher in the hip flexion group [T4 (T8-C6) and T3 (T6 C2)] compared with the control group [T7 (T12-T4) and T5 (T11-T3)] (P < 0.001). The maximum motor blockade median (range) was not different between the two groups being 3 (3-3) in the hip flexion group vs 3 (0-3) in the control group. CONCLUSIONS: When the level of spinal anaesthesia is lower than required, flexion of the hips in the Trendelenburg position may be useful as a strategy attempt to increase the level of the block. PMID- 17283006 TI - Randomized, double-blind comparison of patient-controlled epidural infusion vs nurse-administered epidural infusion for postoperative analgesia in patients undergoing colonic resection. AB - BACKGROUND: There is little published evidence of the analgesic efficacy of patient-controlled epidural analgesia (PCEA) for postoperative pain relief. The aim of this study was to compare the analgesic efficacy of epidural infusion of bupivacaine 0.125% and fentanyl 4 microg ml(-1) administered by either PCEA with a background infusion or nurse-administered continuous epidural infusion (CEI) after major intra-abdominal surgery. METHODS: In a double-blind, randomized clinical trial, 205 adult patients undergoing colonic resection by laparotomy received either PCEA or CEI. Pain scores were recorded via a four-point verbal rating scale at 1, 2, 3, 4, 8, 12, 24, 48, and 72 h after surgery. The administration of epidural top-ups and systemic analgesia over the same period was also recorded, and patient satisfaction questionnaires completed. RESULTS: The median area under the curve of pain against time was significantly lower in the PCEA group (2 vs 24, P<0.001) as were median summary pain scores on movement (0.67 vs 1.33, P<0.001). Significantly fewer patients in the PCEA group received one or more epidural top-ups (13 vs 36%, P = 0.0002) or any systemic analgesics (41 vs 63%, P = 0.0021). Patients in the PCEA group were significantly more likely to be very satisfied than in the CEI group (76 vs 43%, P<0.0001). CONCLUSIONS: PCEA provides greater analgesic efficacy than CEI for postoperative analgesia after major intra-abdominal surgery, and a decreased requirement for physician or nurse intervention. PMID- 17283008 TI - Cell signalling mechanisms and the control of cell life and death. PMID- 17283007 TI - A Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase mutant derivative highly active and stereoselective on phenylacetone and benzylacetone. AB - The secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus 39E (TeSADH) is highly thermostable and solvent-stable, and it is active on a broad range of substrates. These properties make TeSADH an excellent template to engineer an industrial catalyst for chiral chemical synthesis. (S)-1-Phenyl-2 propanol was our target product because it is a precursor to major pharmaceuticals containing secondary alcohol groups. TeSADH has no detectable activity on this alcohol, but it is highly active on 2-butanol. The structural model we used to plan our mutagenesis strategy was based on the substrate's orientation in a horse liver alcohol dehydrogenase*p-bromobenzyl alcohol*NAD(+) ternary complex (PDB entry 1HLD). The W110A TeSADH mutant now uses (S)-1-phenyl-2 propanol, (S)-4-phenyl-2-butanol and the corresponding ketones as substrates. W110A TeSADH's kinetic parameters on these substrates are in the same range as those of TeSADH on 2-butanol, making W110A TeSADH an excellent catalyst. In particular, W110A TeSADH is twice as efficient on benzylacetone as TeSADH is on 2 butanol, and it produces (S)-4-phenyl-2-butanol from benzylacetone with an enantiomeric excess above 99%. W110A TeSADH is optimally active at 87.5 degrees C and remains highly thermostable. W110A TeSADH is active on aryl derivatives of phenylacetone and benzylacetone, making this enzyme a potentially useful catalyst for the chiral synthesis of aryl derivatives of alcohols. As a control in our engineering approach, we used the TbSADH*(S)-2-butanol binary complex (PDB entry 1BXZ) as the template to model a mutation that would make TeSADH active on (S)-1 phenyl-2-propanol. Mutant Y267G TeSADH did not have the substrate specificity predicted in this modeling study. Our results suggest that (S)-2-butanol's orientation in the TbSADH*(S)-2-butanol binary complex does not reflect its orientation in the ternary enzyme-substrate-cofactor complex. PMID- 17283009 TI - Ion-counting nanodosemeter with particle tracking capabilities. AB - An ion-counting nanodosemeter (ND) yielding the distribution of radiation-induced ions in a low-pressure gas within a millimetric, wall-less sensitive volume (SV) was equipped with a silicon microstrip telescope that tracks the primary particles, allowing correlation of nanodosimetric data with particle position relative to the SV. The performance of this tracking ND was tested with a broad 250 MeV proton beam at Loma Linda University Medical Center. The high-resolution tracking capability made it possible to map the ion registration efficiency distribution within the SV, for which only calculated data were available before. It was shown that tracking information combined with nanodosimetric data can map the ionisation pattern of track segments within 150 nm-equivalent long SVs with a longitudinal resolution of approximately 5 tissue-equivalent nanometers. Data acquired in this work were compared with results of Monte Carlo track structure simulations. The good agreement between 'tracking nanodosimetry' data acquired with the new system and simulated data supports the application of ion-counting nanodosimetry in experimental track-structure studies. PMID- 17283010 TI - Biophysics and bioinformatics reveal structural differences of the two peripheral stalk subunits in chloroplast ATP synthase. AB - ATP synthases convert an electrochemical proton gradient into rotational movement to produce the ubiquitous energy currency adenosine triphosphate. Tension generated by the rotational torque is compensated by the stator. For this task, a peripheral stalk flexibly fixes the hydrophilic catalytic part F1 to the membrane integral proton conducting part F(O) of the ATP synthase. While in eubacteria a homodimer of b subunits forms the peripheral stalk, plant chloroplasts and cyanobacteria possess a heterodimer of subunits I and II. To better understand the functional and structural consequences of this unique feature of photosynthetic ATP synthases, a procedure was developed to purify subunit I from spinach chloroplasts. The secondary structure of subunit I, which is not homologous to bacterial b subunits, was compared to heterologously expressed subunit II using CD and FTIR spectroscopy. The content of alpha-helix was determined by CD spectroscopy to 67% for subunit I and 41% for subunit II. In addition, bioinformatics was applied to predict the secondary structure of the two subunits and the location of the putative coiled-coil dimerization regions. Three helical domains were predicted for subunit I and only two uninterrupted domains for the shorter subunit II. The predicted length of coiled-coil regions varied between different species and between subunits I and II. PMID- 17283011 TI - Mutational analysis of the carboxyl-terminal region of the SV40 major capsid protein VP1. AB - Virus-like particles (VLPs), a promising next-generation drug delivery vehicle, can be formed in vitro using a recombinant viral capsid protein VP1 from SV40. Seventy-two VP1 pentamers interconnect to form the T = 7d lattice of SV40 capsids, through three types of C-terminal interactions, alpha-alpha'-alpha'', beta-beta' and gamma-gamma. These appear to require VP1 conformational switch, which involve in particular the region from amino acids 301-312 (herein Region I). Here we show that progressive deletions from the C-terminus of VP1, up to 34 amino acids, cause size and shape variations in the resulting VLPs, including tubular formation, whereas deletions beyond 34 amino acids simply blocked VP1 self-assembly. Mutants carrying in Region I point mutations predicted to disrupt alpha-alpha'-alpha''-type and/or beta-beta'-type interactions formed small VLPs resembling T = 1 symmetry. Chimeric VP1, in which Region I of SV40 VP1 was substituted with the homologous region from VP1 of other polyomaviruses, assembled only into small VLPs. Together, our results show the importance of the integrity of VP1 C-terminal region and the specific amino acid sequences within Region I in the assembly of normal VLPs. By understanding how to alter VLP sizes and shapes contributes to the development of drug delivery systems using VLPs. PMID- 17283012 TI - Molecular cloning of N-methylputrescine oxidase from tobacco. AB - Nicotine biosynthesis in Nicotiana species requires an oxidative deamination of N methylputrescine, catalyzed by N-methylputrescine oxidase (MPO). In a screen for tobacco genes that were down-regulated in a tobacco mutant with altered regulation of nicotine biosynthesis, we identified two homologous MPO cDNAs which encode diamine oxidases of a particular subclass. Tobacco MPO genes were expressed specifically in the root, and up-regulated by jasmonate treatment. Recombinant MPO protein expressed in Escherichia coli formed a homodimer and deaminated N-methylputrescine more efficiently than symmetrical diamines. These results indicate that MPO evolved from general diamine oxidases to function effectively in nicotine biosynthesis. PMID- 17283013 TI - Mapping and characterization of DNase I hypersensitive sites in Arabidopsis chromatin. AB - Recent genome-wide analyses of yeast and human chromatin revealed the widespread prevalence of DNase I hypersensitive sites (DNase I HSs) at gene regulatory regions with possible roles in eukaryotic gene regulation. The presence of DNase I HSs in plants has been described for only a few genes, and we analyzed the chromatin structure of an 80 kb genomic region containing 30 variably expressed genes by DNase I sensitivity assay at 500 bp resolution in Arabidopsis. Distinct DNase I HSs were found at the 5' and/or 3' ends of most genes irrespective of their expression levels. Further analysis of well-characterized genes showed that the DNase I HSs occurred near cis-regulatory elements in the promoters of these genes. Upon transcriptional activation of a heat-inducible gene, the DNase I HS was extended into the vicinity of a cis-element and adjacent TATA element in the promoter. Concomitant with this change in DNase I HS, histones were acetylated, removed from the promoter, and a transcription activator bound to this cis element. These results suggest that the DNase I HSs participate in the transcriptional regulation of Arabidopsis genes by enhancing the access of chromatin remodeling factors and/or transcription factors to their target sites as seen in yeast and human chromatin. PMID- 17283014 TI - Phosphoenolpyruvate carboxykinase in Arabidopsis: changes in gene expression, protein and activity during vegetative and reproductive development. AB - The aim of this work was to investigate the occurrence of phosphoenolpyruvate carboxykinase (PEPCK) in different tissues of Arabidopsis thaliana throughout its vegetative and reproductive growth. The A. thaliana genome contains two PEPCK genes (PCK1 and PCK2), and these are predicted to generate 73,404 and 72,891 Da protein products, respectively. Both genes were transcribed in a range of tissues; however, PCK1 mRNA appeared to be more abundant and was present in a wider range of tissues. PEPCK protein was present in flowers, fruit, developing seed, germinating seed, leaves, stems and roots. Two PEPCK polypeptides, of approximately 74 and approximately 73 kDa were detected by immunoblotting, and these may arise from PCK1 and PCK2, respectively. PEPCK was abundant in cotyledons during post-germinative growth, and this is consistent with its well established role in gluconeogenesis. PEPCK was also abundant in sink tissues, such as young leaves, in developing flowers, fruit and seed. Immunohistochemistry and in situ hybridization showed that PEPCK was present in the nectaries, stigma, endocarp of the fruit wall and in tissues involved in the transfer of assimilates to the developing ovules and seeds, such as the vasculature and seed coat. The potential functions of PEPCK in A. thaliana are discussed. PMID- 17283015 TI - CardioRhythm 2007. Abstracts. PMID- 17283032 TI - Improving antimicrobial prescribing through knowledge and skills. PMID- 17283031 TI - Metabolic profile of a peptide-conjugated chlorin-type photosensitizer targeting neuropilin-1: an in vivo and in vitro study. AB - Because angiogenic endothelial cells of the tumor vasculature represent an interesting target to potentiate the antivascular effect of photodynamic therapy, we recently described the conjugation of a photosensitizer [5-(4-carboxyphenyl) 10,15,20-triphenylchlorin (TPC)], via a spacer [6-aminohexanoic acid (Ahx)], to a vascular endothelial growth factor receptor-specific heptapeptide [H-Ala-Thr-Trp Leu-Pro-Pro-Arg-OH (ATWLPPR)] and showed that TPC-Ahx-ATWLPPR binds to neuropilin 1. Because peptides often display low stability in biological fluids, we examined the in vivo and in vitro stability of this conjugate by high-performance liquid chromatography and matrix-assisted laser desorption ionization/time of flight mass spectrometry. TPC-Ahx-ATWLPPR was stable in vitro in human and mouse plasma for at least 24 h at 37 degrees C but, following i.v. injection in glioma-bearing nude mice, was degraded in vivo to various rates, depending on the organ considered. TPC-Ahx-A was identified as the main metabolic product, and biodistribution studies suggested that its appearance in plasma mainly resulted from the degradation of the peptidic moiety into organs of the reticuloendothelial system. According to in vitro cell culture experiments, TPC Ahx-ATWLPPR was also significantly degraded after incorporation in human umbilical vein endothelial cells (HUVEC), mainly into TPC-Ahx-A and to a lesser extent into TPC-Ahx-AT and TPC-Ahx-ATWLPP. TPC-Ahx-ATWLPPR mostly localized into lysosomes, and when HUVEC were treated with the lysosomal enzymes' inhibitor ammonium chloride, this resulted in a significant decrease of the peptide degradation. This study provides essential information for the choice of the time of activation of the photosensitizer (drug-light interval) not to be exceeded and for the future design of more stable molecules. PMID- 17283033 TI - Treatment of Staphylococcus epidermidis central vascular catheter infection with 70% ethanol locks: efficacy in a sheep model. AB - OBJECTIVES: To determine whether a single treatment with ethanol/water (70:30) will sterilize infected vascular catheters. METHODS: A double-blinded, block randomized trial was conducted in a sheep model comparing the efficacy of one 3 h treatment with ethanol/water (70:30) with heparinized saline for treatment of Hickman vascular catheters infected with Staphylococcus epidermidis. Catheters were cultured using endoluminal brushes, blood cultures, roll plates of catheter tip, broth flushed through the catheter and hub swabs. RESULTS: There were significantly more sterile catheters in the ethanol treatment group than the saline treatment group (9/11 versus 0/11, P < 0.01, McNemar's chi(2) test). The median number of positive cultures in the ethanol treatment group was less than in the saline treatment group (0 versus 5, P = 0.009, Wilcoxon signed-rank test). CONCLUSIONS: A single treatment of 70% ethanol is effective and clinical trials are warranted for treatment of infected vascular catheters using this regimen. PMID- 17283034 TI - Transfer of plasmid and chromosomal glycopeptide resistance determinants occurs more readily in the digestive tract of mice than in vitro and exconjugants can persist stably in vivo in the absence of glycopeptide selection. AB - OBJECTIVES AND METHODS: The transferability of vanA and vanB glycopeptide resistance determinants with a defined plasmid (n = 9) or chromosomal (n = 4) location between Enterococcus faecium strains of human and animal origins was compared using filter mating (in vitro) and germ-free mice (in vivo) as experimental models. Moreover, the stability of exconjugants in vivo in the absence of antibiotic selection was examined. RESULTS: Higher transfer rates were observed in vivo for four of six vanA and five of six vanB donor strains. For plasmid-encoded resistance, several log higher transfer frequencies were observed in vivo for some strains. Moreover, the in vivo model supported transfer of plasmid-encoded vanB (1 x 10(-7) exconjugants/donor) when repeated in vitro experiments were negative (estimated < 1 x 10(-9) exconjugants/donor). Readily detectable transfer of plasmid-located vanA and vanB as well as large chromosomal (>200 kb) vanB elements was observed after 24 h. The number of plasmid-mediated vanA exconjugants generally decreased markedly after 3 days. However, exconjugants containing a plasmid harbouring the vanA transposon Tn1546 linked to the post-segregational killing system omega-epsilon-zeta persisted stably in vivo in the absence of glycopeptides for more than 20 days. CONCLUSIONS: The overall results support the notion that the in vitro model underestimates the transfer potential. Rapid transfer of vanA plasmids from poultry- and pig-derived strains to human faecal E. faecium shows that even transiently colonizing strains may provide a significant reservoir for transfer of resistance genes to the permanent commensal flora. Newly acquired resistance genes may be stabilized and persist in new populations in the absence of antibiotic selection. PMID- 17283035 TI - Can mass media campaigns change antimicrobial prescribing? A regional evaluation study. AB - BACKGROUND: Antimicrobial drug resistance is a significant cause of avoidable morbidity and mortality. Inappropriate prescribing of antimicrobials is acknowledged as a key determinant of this phenomenon. Many approaches are advocated for reducing this inappropriate prescribing, including regulatory, professional and educational interventions. Mass media campaigns are often suggested as a useful tool in managing public expectations, but the evidence to support this is weak, as no controlled studies of such campaigns exist. Evaluating such campaigns is problematic, and uncontrolled observations are misleading. We report here the first controlled study of such an intervention in the use of antimicrobials. METHODS: Two sequential mass media campaigns, providing information on the appropriate use of antimicrobials, were conducted during early 2004 and 2005 in the North East of England. These messages were articulated in the campaign by the cartoon character 'Moxy Malone'. The campaigns were supported by printed materials, and in parts of this area, with professional education and prescribing support. A retrospective controlled before-after study was conducted, examining the effects on observed prescribing of antimicrobials for the populations covered by these two cycles of mass media campaigns. These populations were controlled with matched populations in the North of England. The primary outcome examined was prescribing rates (items) for all microbial agents for these populations, corrected for population structure (STAR-PU). A repeated measures analysis of variance (ANOVA) was used to analyse factors that had a possible effect on the prescribing of antibacterial drugs. This was supported by a survey of primary care organizations (PCOs) of all interventions undertaken around antimicrobial use in the intervention and comparison populations. RESULTS: In this retrospective study, there was incomplete reporting of adjuvant interventions undertaken by the PCOs intervention and comparison areas, so isolating the intervention, and attributing cause and effect is difficult. In this pragmatic evaluation the campaign was found to significantly reduce the volume of antibacterial drugs during the winter months of the intervention years. There were 21.7 fewer items prescribed per 1000 population (P < 0.0005), for the intervention populations over these winter months, equivalent to a 5.8% absolute reduction in prescribing. CONCLUSIONS: Mass media campaigns have a role in changing antimicrobial prescribing practice. PMID- 17283036 TI - Characterization of side-population cells in human normal endometrium. AB - BACKGROUND: It has been proposed that the human endometrium may contain a population of adult stem cells that are responsible for its remarkable regenerative capability. Recently, a subset of stem cells or progenitor cells in adult tissue has been identified as side-population cells (SP cells) displaying low staining with Hoechst 33342 by fluorescence-activated cell sorter (FACS) analysis. In this study, we isolated SP cells from the human endometrium and analysed their properties. METHOD: Endometrial cells were obtained using enzymatic digestion from uterine hysterectomy for the treatment of uterine myoma and stained with Hoechst 33342 dye either alone or in combination with verapamil. The cells were then analysed using FACS. RESULTS: SP cells were present among normal human endometrial cells. Most SP cells were enriched in the CD9(-)CD13(-) fraction. These SP cells showed long-term repopulating properties and produced gland (CD9(+))- and stroma (CD13(+))-like cells. CD9(-)CD13(-) cells isolated from the endometrium also generated gland- or stroma-like cells. CONCLUSIONS: SP cells in the human endometrium can function as progenitor cells. This is the first report of the phenotype of SP cells from normal human endometrial cells. PMID- 17283037 TI - Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities. AB - BACKGROUND: We have recently suggested that homozygosity for a specific 'AGATA' haplotype within a approximately 50 kb linkage disequilibrium (LD) block of the gene for estrogen receptor alpha (ESR1) may raise the susceptibility to cryptorchidism by enhancing estrogenic effects of environmental endocrine disruptors (EEDs). METHODS: Haplotype analysis of ESR1 was performed in 328 Japanese subjects, i.e. 70 patients with micropenis (MP), 43 patients with hypospadias (HS), 80 patients with spermatogenic failure (SF) and 135 control males. Genotyping was performed by the 5' nuclease assay. RESULTS: The LD block was identified in each of the patient groups and in the control males. The frequency of homozygotes for the specific 'AGATA' haplotype was markedly higher in the HS patients [P = 0.0000033, odds ratio [OR] = 11.26] and slightly higher in the MP patients (P = 0.034, OR = 3.64) than in the control males, and the 'AGATA' haplotype was strongly associated with HS (P = 0.0000022, OR = 11.26) and weakly associated with MP (P = 0.040, OR = 3.64) in a recessive mode. There was no significant difference between the SF patients and the control males. CONCLUSIONS: Our results support the hypothesis that homozygosity for the specific ESR1 'AGATA' haplotype may increase the susceptibility to the development of male genital abnormalities in response to estrogenic EEDs. PMID- 17283038 TI - Complex chromosomal rearrangement and intracytoplasmic sperm injection: a case report. AB - Complex chromosomal rearrangements (CCRs) are rare events in human pathology and are usually considered to induce severe reproductive impairment by disturbing the meiotic process and producing unbalanced gametes responsible for high reproductive risk. One-third of all CCRs are familial and tend to implicate fewer breakpoints and fewer chromosomes than de novo cases. CCRs are rarely transmitted through spermatogenesis and are primarily ascertained by male infertility. We report a familial balanced CCR, with seven breakpoints involving three chromosomes, which was detected prenatally in a female fetus conceived after intracytoplasmic sperm injection (ICSI) in a couple initially thought to be a carrier of a paternal reciprocal translocation involving two chromosomal breakpoints. Fluorescent in-situ hybridization (FISH) was used to elucidate the complexity of this CCR. The karyotype of the female CCR carrier was balanced and determined as 46,XX.ish t(1;4)(q42;q32)(WCP1+, D1Z5+, WCP4+, D1S3738-, D4S2930+; WCP4+, D4Z1+, WCP1+, D4S2930-, D1S3738+), ins(1;11)(q41;q23q24)(WCP1+,WCP11+, D11S2071-, MLL+; WCP11+, D11S2071+, WCP1-, MLL-), ins(4;11)(q23;q14q23)(WCP4+,WCP11+; WCP11+,WCP4-). The same balanced CCR was confirmed in her oligozoospermic father. We report, to our knowledge, the first case of ICSI performed in an infertile male with CCR, resulting in a balanced CCR carrier female with a normal clinical follow-up at 4 years of age. This particular case stresses the point of the relevance and feasibility of ICSI procedure in cases of balanced CCRs. PMID- 17283039 TI - Letter to the Glyco-Forum: catalytic domains of glycosyltransferases with 'add on' domains. PMID- 17283040 TI - Methylation-controlled J protein promotes c-Jun degradation to prevent ABCB1 transporter expression. AB - Methylation-controlled J protein (MCJ) is a newly identified member of the DnaJ family of cochaperones. Hypermethylation-mediated transcriptional silencing of the MCJ gene has been associated with increased chemotherapeutic resistance in ovarian cancer. However, the biology and function of MCJ remain unknown. Here we show that MCJ is a type II transmembrane cochaperone localized in the Golgi network and present only in vertebrates. MCJ is expressed in drug-sensitive breast cancer cells but not in multidrug-resistant cells. The inhibition of MCJ expression increases resistance to specific drugs by inducing expression of the ABCB1 drug transporter that prevents intracellular drug accumulation. The induction of ABCB1 gene expression is mediated by increased levels of c-Jun due to an impaired degradation of this transcription factor in the absence of MCJ. Thus, MCJ is required in these cells to prevent c-Jun-mediated expression of ABCB1 and maintain drug response. PMID- 17283041 TI - The 3BP2 adapter protein is required for optimal B-cell activation and thymus independent type 2 humoral response. AB - 3BP2 is a pleckstrin homology domain- and Src homology 2 (SH2) domain-containing adapter protein that is mutated in the rare human bone disorder cherubism and which has also been implicated in immunoreceptor signaling. However, a function for this protein has yet to be established. Here we show that mice lacking 3BP2 exhibited a perturbation in the peritoneal B1 and splenic marginal-zone B-cell compartments and diminished thymus-independent type 2 antigen response. 3BP2(-/-) B cells demonstrated a proliferation defect in response to antigen receptor cross linking and a heightened sensitivity to B-cell receptor-induced death via a caspase-3-dependent apoptotic pathway. We show that 3BP2 binds via its SH2 domain to the CD19 signaling complex and is required for optimum Syk phosphorylation and calcium flux. PMID- 17283042 TI - Early embryonic lethality of mice lacking the essential protein SNEV. AB - SNEV (Prp19, Pso4, NMP200) is a nuclear matrix protein known to be involved in pre-mRNA splicing, ubiquitylation, and DNA repair. In human umbilical vein endothelial cells, SNEV overexpression delayed the onset of replicative senescence. Here we analyzed the function of the mouse SNEV gene in vivo by employing homologous recombination in mice and conclude that SNEV is indispensable for early mouse development. Mutant preimplantation embryos initiated blastocyst formation but died shortly thereafter. Outgrowth of SNEV null blastocysts showed a lack of proliferation of cells of the inner cell mass, which subsequently underwent cell death. While SNEV-heterozygous mice showed no overt phenotype, heterozygous mouse embryonic fibroblast cell lines with reduced SNEV levels displayed a decreased proliferative potential in vitro. Our experiments demonstrate that the SNEV protein is essential, functionally nonredundant, and indispensable for mouse development. PMID- 17283044 TI - A modular enhancer is differentially regulated by GATA and NFAT elements that direct different tissue-specific patterns of nucleosome positioning and inducible chromatin remodeling. AB - We investigated alternate mechanisms employed by enhancers to position and remodel nucleosomes and activate tissue-specific genes in divergent cell types. We demonstrated that the granulocyte-macrophage colony-stimulating factor (GM CSF) gene enhancer is modular and recruits different sets of transcription factors in T cells and myeloid cells. The enhancer recruited distinct inducible tissue-specific enhanceosome-like complexes and directed nucleosomes to different positions in these cell types. In undifferentiated T cells, the enhancer was activated by inducible binding of two NFAT/AP-1 complexes which disrupted two specifically positioned nucleosomes (N1 and N2). In myeloid cells, the enhancer was remodeled by GATA factors which constitutively displaced an upstream nucleosome (N0) and cooperated with inducible AP-1 elements to activate transcription. In mast cells, which express both GATA-2 and NFAT, these two pathways combined to activate the enhancer and generate high-level gene expression. At least 5 kb of the GM-CSF locus was organized as an array of nucleosomes with fixed positions, but the enhancer adopted different nucleosome positions in T cells and mast cells. Furthermore, nucleosomes located between the enhancer and promoter were mobilized upon activation in an enhancer-dependent manner. These studies reveal that distinct tissue-specific mechanisms can be used either alternately or in combination to activate the same enhancer. PMID- 17283043 TI - Disruption of the FEN-1/PCNA interaction results in DNA replication defects, pulmonary hypoplasia, pancytopenia, and newborn lethality in mice. AB - The interaction between flap endonuclease 1 (FEN-1) and proliferation cell nuclear antigen (PCNA) is critical for faithful and efficient Okazaki fragment maturation. In a living cell, this interaction is probably important for PCNA to load FEN-1 to the replication fork, to coordinate the sequential functions of FEN 1 and other enzymes, and to stimulate its enzyme activity. The FEN-1/PCNA interaction is mediated by the motif (337)QGRLDDFFK(345) of FEN-1, such that an F343AF344A (FFAA) mutant cannot bind to PCNA but retains its nuclease activities. To determine the physiological roles of the FEN-1/PCNA interaction in a mammalian system, we knocked the FFAA Fen1 mutation into the Fen1 gene locus of mice. FFAA/FFAA mouse embryo fibroblasts underwent DNA replication and division at a slower pace, and FFAA/FFAA mutant embryos displayed significant defects in growth and development, particularly in the lung and blood systems. All newborn FFAA mutant pups died at birth, likely due to pulmonary hypoplasia and pancytopenia. Collectively, our data demonstrate the importance of the FEN-1/PCNA complex in DNA replication and in the embryonic development of mice. PMID- 17283045 TI - Rbm15 modulates Notch-induced transcriptional activation and affects myeloid differentiation. AB - RBM15 is the fusion partner with MKL in the t(1;22) translocation of acute megakaryoblastic leukemia. To understand the role of the RBM15-MKL1 fusion protein in leukemia, we must understand the normal functions of RBM15 and MKL. Here, we show a role for Rbm15 in myelopoiesis. Rbm15 is expressed at highest levels in hematopoietic stem cells and at more moderate levels during myelopoiesis of murine cell lines and primary murine cells. Decreasing Rbm15 levels with RNA interference enhances differentiation of the 32DWT18 myeloid precursor cell line. Conversely, enforced expression of Rbm15 inhibits 32DWT18 differentiation. We show that Rbm15 alters Notch-induced HES1 promoter activity in a cell type-specific manner. Rbm15 inhibits Notch-induced HES1 transcription in nonhematopoietic cells but stimulates this activity in hematopoietic cell lines, including 32DWT18 and human erythroleukemia cells. Moreover, the N terminus of Rbm15 coimmunoprecipitates with RBPJkappa, a critical factor in Notch signaling, and the Rbm15 N terminus has a dominant negative effect, impairing activation of HES1 promoter activity by full-length-Rbm15. Thus, Rbm15 is differentially expressed during hematopoiesis and may act to inhibit myeloid differentiation in hematopoietic cells via a mechanism that is mediated by stimulation of Notch signaling via RBPJkappa. PMID- 17283046 TI - c-Jun homodimers can function as a context-specific coactivator. AB - Transcription factors can function as DNA-binding-specific activators or as coactivators. c-Jun drives gene expression via binding to AP-1 sequences or as a cofactor for PU.1 in macrophages. c-Jun heterodimers bind AP-1 sequences with higher affinity than homodimers, but how c-Jun works as a coactivator is unknown. Here, we provide in vitro and in vivo evidence that c-Jun homodimers are recruited to the interleukin-1beta (IL-1beta) promoter in the absence of direct DNA binding via protein-protein interactions with DNA-anchored PU.1 and CCAAT/enhancer-binding protein beta (C/EBPbeta). Unexpectedly, the interaction interface with PU.1 and C/EBPbeta involves four of the residues within the basic domain of c-Jun that contact DNA, indicating that the capacities of c-Jun to function as a coactivator or as a DNA-bound transcription factor are mutually exclusive. Our observations indicate that the IL-1beta locus is occupied by PU.1 and C/EBPbeta and poised for expression and that c-Jun enhances transcription by facilitating a rate-limiting step, the assembly of the RNA polymerase II preinitiation complex, with minimal effect on the local chromatin status. We propose that the basic domain of other transcription factors may also be redirected from a DNA interaction mode to a protein-protein interaction mode and that this switch represents a novel mechanism regulating gene expression profiles. PMID- 17283047 TI - Mitogenic activity and signaling mechanism of 2-(14,15- epoxyeicosatrienoyl)glycerol, a novel cytochrome p450 arachidonate metabolite. AB - Arachidonic acid is an essential constituent of cell membranes that is esterified to the sn-2 position of glycerophospholipids and is released from selected phospholipid pools by tightly regulated phospholipase cleavage. Metabolism of the released arachidonic acid by the cytochrome P450 enzyme system (cP450) generates biologically active compounds, including epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids. Here we report that 2-(14,15 epoxyeicosatrienoyl)glycerol (2-14,15-EG), a novel cP450 arachidonate metabolite produced in the kidney, is a potent mitogen for renal proximal tubule cells. This effect is mediated by activation of tumor necrosis factor alpha-converting enzyme (ADAM17), which cleaves membrane-bound transforming growth factor alpha (proTGF alpha) and releases soluble TGF-alpha as a ligand that binds and activates epidermal growth factor receptor (EGFR). The present studies additionally demonstrate that the structurally related 14,15-EET stimulates release of soluble heparin-binding EGF-like growth factor as an EGFR ligand by activation of ADAM9, another member of the ADAM family. Thus, in addition to the characterization of 2 14,15-EG's mitogenic activity and signaling mechanism, our study provides the first example that two structurally related biologically active lipid mediators can activate different metalloproteinases and release different EGFR ligands in the same cell type to activate EGFR and stimulate cell proliferation. PMID- 17283049 TI - Glycogen synthase kinase 3beta phosphorylates p21WAF1/CIP1 for proteasomal degradation after UV irradiation. AB - UV irradiation has been reported to induce p21(WAF1/CIP1) protein degradation through a ubiquitin-proteasome pathway, but the underlying biochemical mechanism remains to be elucidated. Here, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3beta (GSK-3beta) is required for its degradation in response to UV irradiation and that GSK-3beta activation is a downstream event in the ATR signaling pathway triggered by UV. UV transiently increased GSK-3beta activity, and this increase could be blocked by caffeine or by ATR small interfering RNA, indicating ATR-dependent activation of GSK-3beta. ser-114, located within the putative GSK-3beta target sequence, was phosphorylated by GSK-3beta upon UV exposure. The nonphosphorylatable S114A mutant of p21 was protected from UV-induced destabilization. Degradation of p21 protein by UV irradiation was independent of p53 status and prevented by proteasome inhibitors. In contrast to the previous report, the proteasomal degradation of p21 appeared to be ubiquitination independent. These data show that GSK-3beta is activated by UV irradiation through the ATR signaling pathway and phosphorylates p21 at ser-114 for its degradation by the proteasome. To our knowledge, this is the first demonstration of GSK-3beta as the missing link between UV-induced ATR activation and p21 degradation. PMID- 17283048 TI - Beta-globin intergenic transcription and histone acetylation dependent on an enhancer. AB - Histone acetyltransferases are associated with the elongating RNA polymerase II (Pol II) complex, supporting the idea that histone acetylation and transcription are intertwined mechanistically in gene coding sequences. Here, we studied the establishment and function of histone acetylation and transcription in noncoding sequences by using a model locus linking the beta-globin HS2 enhancer and the embryonic epsilon-globin gene in chromatin. An intact HS2 enhancer that recruits RNA Pol II is required for intergenic transcription and histone H3 acetylation and K4 methylation between the enhancer and target gene. RNA Pol II recruitment to the target gene TATA box is not required for the intergenic transcription or intergenic histone modifications, strongly implying that they are properties conferred by the enhancer. However, Pol II recruitment at HS2, intergenic transcription, and intergenic histone modification are not sufficient for transcription or modification of the target gene: these changes require initiation at the TATA box of the gene. The results suggest that intergenic and genic transcription complexes are independent and possibly differ from one another. PMID- 17283050 TI - The Isw2 chromatin-remodeling ATPase cooperates with the Fkh2 transcription factor to repress transcription of the B-type cyclin gene CLB2. AB - Forkhead (Fkh) transcription factors influence cell death, proliferation, and differentiation and the cell cycle. In Saccharomyces cerevisiae, Fkh2 both activates and represses transcription of CLB2, encoding a B-type cyclin. CLB2 is expressed during G(2)/M phase and repressed during G(1). Fkh2 recruits the coactivator Ndd1, an interaction which is promoted by Clb2/Cdk1-dependent phosphorylation of Ndd1, suggesting that CLB2 is autoregulated. Ndd1 is proposed to function by antagonizing Fkh2-mediated repression, but nothing is known about the mechanism. Here we ask how Fkh2 represses CLB2. We show that Fkh2 controls a repressive chromatin structure that initiates in the early coding region of CLB2 and spreads up the promoter during the M and G(1) phases. The Isw2 chromatin remodeling ATPase cooperates with Fkh2 to remodel the chromatin and repress CLB2 expression throughout the cell cycle. In addition, the related factors Isw1 and Fkh1 configure the chromatin at the early coding region and negatively regulate CLB2 expression but only during G(2)/M phase. Thus, the cooperative actions of two forkhead transcription factors and two chromatin-remodeling ATPases combine to regulate CLB2. We propose that chromatin-mediated repression by Isw1 and Isw2 may serve to limit activation of CLB2 expression by the Clb2/Cdk1 kinase during G(2)/M and to fully repress expression during G(1). PMID- 17283051 TI - Study of the functional interaction between Mcp insulators from the Drosophila bithorax complex: effects of insulator pairing on enhancer-promoter communication. AB - Boundary elements have been found in the Abd-B 3' cis-regulatory region, which is subdivided into a series of iab domains. Previously, a 340-bp insulator-like element, M(340), was identified in one such 755-bp Mcp fragment linked to the PcG dependent silencer. In this study, we identified a 210-bp core that was sufficient for pairing of sequence-remote Mcp elements. In two-gene transgenic constructs with two Mcp insulators (or their cores) surrounding yellow, the upstream yeast GAL4 sites were able to activate the distal white only if the insulators were in the opposite orientations (head-to-head or tail-to-tail), which is consistent with the looping/bypass model. The same was true for the efficiency of the cognate eye enhancer, while yellow thus isolated in the loop from its enhancers was blocked more strongly. These results indicate that the relative placement and orientation of insulator-like elements can determine proper enhancer-promoter communication. PMID- 17283053 TI - Cooperative roles of vertebrate Fbh1 and Blm DNA helicases in avoidance of crossovers during recombination initiated by replication fork collapse. AB - Fbh1 (F-box DNA helicase 1) orthologues are conserved from Schizosaccharomyces pombe to chickens and humans. Here, we report the disruption of the FBH1 gene in DT40 cells. Although the yeast fbh1 mutant shows an increase in sensitivity to DNA damaging agents, FBH1(-)(/)(-) DT40 clones show no prominent sensitivity, suggesting that the loss of FBH1 might be compensated by other genes. However, FBH1(-)(/)(-) cells exhibit increases in both sister chromatid exchange and the formation of radial structures between homologous chromosomes without showing a defect in homologous recombination. This phenotype is reminiscent of BLM(-)(/)(-) cells and suggests that Fbh1 may be involved in preventing extensive strand exchange during homologous recombination. In addition, disruption of RAD54, a major homologous recombination factor in FBH1(-)(/)(-) cells, results in a marked increase in chromosome-type breaks (breaks on both sister chromatids at the same place) following replication fork arrest. Further, FBH1BLM cells showed additive increases in both sister chromatid exchange and the formation of radial chromosomes. These data suggest that Fbh1 acts in parallel with Bloom helicase to control recombination-mediated double-strand-break repair at replication blocks and to reduce the frequency of crossover. PMID- 17283052 TI - Role of the Orc6 protein in origin recognition complex-dependent DNA binding and replication in Drosophila melanogaster. AB - The six-subunit origin recognition complex (ORC) is a DNA replication initiator protein in eukaryotes that defines the localization of the origins of replication. We report here that the smallest Drosophila ORC subunit, Orc6, is a DNA binding protein that is necessary for the DNA binding and DNA replication functions of ORC. Orc6 binds DNA fragments containing Drosophila origins of DNA replication and prefers poly(dA) sequences. We have defined the core replication domain of the Orc6 protein which does not include the C-terminal domain. Further analysis of the core replication domain identified amino acids that are important for DNA binding by Orc6. Alterations of these amino acids render reconstituted Drosophila ORC inactive in DNA binding and DNA replication. We show that mutant Orc6 proteins do not associate with chromosomes in vivo and have dominant negative effects in Drosophila tissue culture cells. Our studies provide a molecular analysis for the functional requirement of Orc6 in replicative functions of ORC in Drosophila and suggest that Orc6 may contribute to the sequence preferences of ORC in targeting to the origins. PMID- 17283054 TI - Thio modification of yeast cytosolic tRNA is an iron-sulfur protein-dependent pathway. AB - Defects in the yeast cysteine desulfurase Nfs1 cause a severe impairment in the 2 thio modification of uridine of mitochondrial tRNAs (mt-tRNAs) and cytosolic tRNAs (cy-tRNAs). Nfs1 can also provide the sulfur atoms of the iron-sulfur (Fe/S) clusters generated by the mitochondrial and cytosolic Fe/S cluster assembly machineries, termed ISC and CIA, respectively. Therefore, a key question remains as to whether the biosynthesis of Fe/S clusters is a prerequisite for the 2-thio modification of the tRNAs in both of the subcellular compartments of yeast cells. To elucidate this question, we asked whether mitochondrial ISC and/or cytosolic CIA components besides Nfs1 were involved in the 2-thio modification of these tRNAs. We demonstrate here that the three CIA components, Cfd1, Nbp35, and Cia1, are required for the 2-thio modification of cy-tRNAs but not of mt-tRNAs. Interestingly, the mitochondrial scaffold proteins Isu1 and Isu2 are required for the 2-thio modification of the cy-tRNAs but not of the mt-tRNAs, while mitochondrial Nfs1 is required for both 2-thio modifications. These results clearly indicate that the 2-thio modification of cy-tRNAs is Fe/S protein dependent and thus requires both CIA and ISC machineries but that of mt-tRNAs is Fe/S cluster independent and does not require key mitochondrial ISC components except for Nfs1. PMID- 17283055 TI - Fibrocystin/polyductin, found in the same protein complex with polycystin-2, regulates calcium responses in kidney epithelia. AB - Recent evidence suggests that fibrocystin/polyductin (FPC), polycystin-1 (PC1), and polycystin-2 (PC2) are all localized at the plasma membrane and the primary cilium, where PC1 and PC2 contribute to fluid flow sensation and may function in the same mechanotransduction pathways. To further define the exact subcellular localization of FPC, the protein product encoded by the PKHD1 gene responsible for autosomal recessive polycystic kidney disease (PKD) in humans, and whether FPC has direct and/or indirect cross talk with PC2, which, in turn, is pivotal for the pathogenesis of autosomal dominant PKD, we performed double immunostaining and coimmunoprecipitation as well as a microfluorimetry study of kidney tubular epithelial cells. FPC and PC2 are found to completely or partially colocalize at the plasma membrane and the primary cilium and can be reciprocally coimmunoprecipitated. Although incomplete removal of FPC by small interfering RNA and antibody 803 to intracellular epitopes of FPC did not abolish flow-induced intracellular calcium responses, antibody 804 to extracellular epitopes of FPC blocked cellular calcium responses to flow stimulation. These findings suggest that FPC and polycystins share, at least in part, a common mechanotransduction pathway. PMID- 17283056 TI - The SR family proteins B52 and dASF/SF2 modulate development of the Drosophila visual system by regulating specific RNA targets. AB - Deciphering the role of alternative splicing in developmental processes relies on the identification of key genes whose expression is controlled by splicing regulators throughout the growth of a whole organism. Modulating the expression levels of five SR proteins in the developing eye of Drosophila melanogaster revealed that these splicing factors induce various phenotypic alterations in eye organogenesis and also affect viability. Although the SR proteins dASF/SF2 and B52 caused defects in ommatidia structure, only B52 impaired normal axonal projections of photoreceptors and neurogenesis in visual ganglia. Microarray analyses revealed that many transcripts involved in brain organogenesis have altered splicing profiles upon both loss and gain of B52 function. Conversely, a large proportion of transcripts regulated by dASF/SF2 are involved in eye development. These differential and specific effects of SR proteins indicate that they function to confer accuracy to developmental gene expression programs by facilitating the cell lineage decisions that underline the generation of tissue identities. PMID- 17283057 TI - The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N terminal kinase-mediated insulin resistance. AB - Insulin resistance is a defining feature of type 2 diabetes and the metabolic syndrome. While the molecular mechanisms of insulin resistance are multiple, recent evidence suggests that attenuation of insulin signaling by c-Jun N terminal kinase (JNK) may be a central part of the pathobiology of insulin resistance. Here we demonstrate that the p85alpha regulatory subunit of phosphoinositide 3-kinase (PI3K), a key mediator of insulin's metabolic actions, is also required for the activation of JNK in states of insulin resistance, including high-fat diet-induced obesity and JNK1 overexpression. The requirement of the p85alpha regulatory subunit for JNK occurs independently of its role as a component of the PI3K heterodimer and occurs only in response to specific stimuli, namely, insulin and tunicamycin, a chemical that induces endoplasmic reticulum stress. We further show that insulin and p85 activate JNK by via cdc42 and MKK4. The activation of this cdc42/JNK pathway requires both an intact N terminus and functional SH2 domains within the C terminus of the p85alpha regulatory subunit. Thus, p85alpha plays a dual role in regulating insulin sensitivity and may mediate cross talk between the PI3K and stress kinase pathways. PMID- 17283058 TI - Role for furin in tumor necrosis factor alpha-induced activation of the matrix metalloproteinase/sphingolipid mitogenic pathway. AB - Neutral sphingomyelinase (nSMase), the initial enzyme of the sphingolipid signaling pathway, is thought to play a key role in cellular responses to tumor necrosis factor alpha (TNF-alpha), such as inflammation, proliferation, and apoptosis. The mechanism of TNF-alpha-induced nSMase activation is only partly understood. Using biochemical, molecular, and pharmacological approaches, we found that nSMase activation triggered by TNF-alpha is required for TNF-alpha induced proliferation and in turn requires a proteolytic cascade involving furin, membrane type 1 matrix metalloproteinase (MT1-MMP), and MMP2, and leading finally to extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and DNA synthesis, in smooth muscle cells (SMC) and fibroblasts. Pharmacological and molecular inhibitors of MMPs (batimastat), furin (alpha1-PDX inhibitor transfected SMC), MT1-MMP (SMC overexpressing a catalytically inactive MT1-MMP), MMP2 (fibroblasts from MMP2(-/-) mice), and small interfering RNA (siRNA) strategies (siRNAs targeting furin, MT1-MMP, MMP2, and nSMase) resulted in near complete inhibition of the activation of nSMase, sphingosine kinase-1, and ERK1/2 and of subsequent DNA synthesis. Exogenous MT1-MMP activated nSMase and SMC proliferation in normal but not in MMP2(-/-) fibroblasts, whereas exogenous MMP2 was active on both normal and MMP2(-/-) fibroblasts. Altogether these findings highlight a pivotal role for furin, MT1-MMP, and MMP2 in TNF-alpha-induced sphingolipid signaling, and they identify this system as a possible target to inhibit SMC proliferation in vascular diseases. PMID- 17283059 TI - Bmp2 transcription in osteoblast progenitors is regulated by a distant 3' enhancer located 156.3 kilobases from the promoter. AB - Bone morphogenetic protein 2 (encoded by Bmp2) has been implicated as an important signaling ligand for osteoblast differentiation and bone formation and as a genetic risk factor for osteoporosis. To initially survey a large genomic region flanking the mouse Bmp2 gene for cis-regulatory function, two bacterial artificial chromosome (BAC) clones that extend far upstream and downstream of the gene were engineered to contain a lacZ reporter cassette and tested in transgenic mice. Each BAC clone directs a distinct subset of normal Bmp2 expression patterns, suggesting a modular arrangement of distant Bmp2 regulatory elements. Strikingly, regulatory sequences required for Bmp2 expression in differentiating osteoblasts, as well as tooth buds, hair placodes, kidney, and other tissues, are located more than 53 kilobases 3' to the promoter. By testing BACs with engineered deletions across this distant 3' region, we parsed these regulatory elements into separate locations and more closely refined the location of the osteoblast progenitor element. Finally, a conserved osteoblast progenitor enhancer was identified within a 656-bp sequence located 156.3 kilobases 3' from the promoter. The identification of this enhancer should permit further investigation of upstream regulatory mechanisms that control Bmp2 transcription during osteoblast differentiation and are relevant to further studies of Bmp2 as a candidate risk factor gene for osteoporosis. PMID- 17283060 TI - Cdh1-anaphase-promoting complex targets Skp2 for destruction in transforming growth factor beta-induced growth inhibition. AB - As a subunit of a ubiquitin ligase, Skp2 is implicated in facilitating cell cycle progression via degradation of various protein targets. We report here that Skp2 is rapidly degraded following cellular stimulation by the cytokine transforming growth factor beta (TGF-beta) and that this degradation stabilizes the cell cycle arrest protein p27. The Skp2 degradation is mediated by Cdh1-anaphase-promoting complex (APC), as shown by depletion of Cdh1 with small interfering RNA, and by reconstitution of ubiquitylation reactions in a purified system. Blockage of Skp2 degradation greatly reduces TGF-beta-induced cell cycle arrest, as does expression of a nondegradable Skp2 mutant. Furthermore, we demonstrate that TGF beta-induced Skp2 degradation is mediated by the Smad cascade. The degradation of Skp2 stabilizes p27, thereby ensuring TGF-beta-induced cell cycle arrest. These results identify a novel mechanism for tumor suppression by TGF-beta and explain why dysfunction of APC in the TGF-beta pathway in responsive cells is associated with cancer. PMID- 17283061 TI - Dependency of ISW1a chromatin remodeling on extranucleosomal DNA. AB - The nucleosome remodeling activity of ISW1a was dependent on whether ISW1a was bound to one or both extranucleosomal DNAs. ISW1a preferentially bound nucleosomes with an optimal length of approximately 33 to 35 bp of extranucleosomal DNA at both the entry and exit sites over nucleosomes with extranucleosomal DNA at only one entry or exit site. Nucleosomes with extranucleosomal DNA at one of the entry/exit sites were readily remodeled by ISW1a and stimulated the ATPase activity of ISW1a, while conversely, nucleosomes with extranucleosomal DNA at both entry/exit sites were unable either to stimulate the ATPase activity of ISW1a or to be mobilized. DNA footprinting revealed that a major conformational difference between the nucleosomes was the lack of ISW1a binding to nucleosomal DNA two helical turns from the dyad axis in nucleosomes with extranucleosomal DNA at both entry/exit sites. The Ioc3 subunit of ISW1a was found to be the predominant subunit associated with extranucleosomal DNA when ISW1a is bound either to one or to both extranucleosomal DNAs. These two conformations of the ISW1a-nucleosome complex are suggested to be the molecular basis for the nucleosome spacing activity of ISW1a on nucleosomal arrays. ISW1b, the other isoform of ISW1, does not have the same dependency for extranucleosomal DNA as ISW1a and, likewise, is not able to space nucleosomes. PMID- 17283062 TI - Identification of Rkr1, a nuclear RING domain protein with functional connections to chromatin modification in Saccharomyces cerevisiae. AB - Proper transcription by RNA polymerase II is dependent on the modification state of the chromatin template. The Paf1 complex is associated with RNA polymerase II during transcription elongation and is required for several histone modifications that mark active genes. To uncover additional factors that regulate chromatin or transcription, we performed a genetic screen for mutations that cause lethality in the absence of the Paf1 complex component Rtf1. Our results have led to the discovery of a previously unstudied gene, RKR1. Strains lacking RKR1 exhibit phenotypes associated with defects in transcription and chromatin function. These phenotypes include inositol auxotrophy, impaired telomeric silencing, and synthetic lethality with mutations in SPT10, a gene that encodes a putative histone acetyltransferase. In addition, deletion of RKR1 causes severe genetic interactions with mutations that prevent histone H2B lysine 123 ubiquitylation or histone H3 lysine 4 methylation. RKR1 encodes a conserved nuclear protein with a functionally important RING domain at its carboxy terminus. In vitro experiments indicate that Rkr1 possesses ubiquitin-protein ligase activity. Taken together, our results identify a new participant in a protein ubiquitylation pathway within the nucleus that acts to modulate chromatin function and transcription. PMID- 17283063 TI - Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes. AB - Ras activation is crucial for lymphocyte development and effector function. Both T and B lymphocytes contain two types of Ras activators: ubiquitously expressed SOS and specifically expressed Ras guanyl nucleotide-releasing protein (RasGRP). The need for two activators is enigmatic since both are activated following antigen receptor stimulation. In addition, RasGRP1 appears to be dominant over SOS in an unknown manner. The crystal structure of SOS provides a clue: an unusual allosteric Ras-GTP binding pocket. Here, we demonstrate that RasGRP orchestrates Ras signaling in two ways: (i) by activating Ras directly and (ii) by facilitating priming of SOS with RasGTP that binds the allosteric pocket. Priming enhances SOS' in vivo activity and creates a positive RasGTP-SOS feedback loop that functions as a rheostat for Ras activity. Without RasGRP1, initiation of this loop is impaired because SOS' catalyst is its own product (RasGTP)-hence the dominance of RasGRP1. Introduction of an active Ras-like molecule (RasV12C40) in T- and B-cell lines can substitute for RasGRP function and enhance SOS' activity via its allosteric pocket. The unusual RasGRP-SOS interplay results in sensitive and robust Ras activation that cannot be achieved with either activator alone. We hypothesize that this mechanism enables lymphocytes to maximally respond to physiologically low levels of stimulation. PMID- 17283064 TI - Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption. AB - Aquaporin 2 (AQP2) is responsible for regulating the concentration of urine in the collecting tubules of the kidney under the control of vasopressin (Vp). Studies using Vp-deficient Brattleboro rats, however, indicated the existence of substantial Vp-independent mechanisms for membrane insertion, as well as transcriptional regulation, of this water channel. The Vp-independent mechanism(s) is clinically relevant to patients with X-linked nephrogenic diabetes insipidus (NDI) by therapeutically bypassing the dysfunctional Vp receptor. On the basis of studies with secretin receptor-null (SCTR(-/-)) mice, we report here for the first time that mutation of the SCTR gene could lead to mild polydipsia and polyuria. Additionally, SCTR(-/-) mice were shown to have reduced renal expression of AQP2 and AQP4, as well as altered glomerular and tubular morphology, suggesting possible disturbances in the filtration and/or water reabsorption process in these animals. By using SCTR(-/-) mice as controls and comparing them with wild-type animals, we performed both in vivo and in vitro studies that demonstrated a role for secretin in stimulating (i) AQP2 translocation from intracellular vesicles to the plasma membrane in renal medullary tubules and (ii) expression of this water channel under hyperosmotic conditions. The present study therefore provides information for at least one of the Vp-independent mechanisms that modulate the process of renal water reabsorption. Future investigations in this direction should be important in developing therapeutic means for treating NDI patients. PMID- 17283065 TI - Erythroid Kruppel-like factor directly activates the basic Kruppel-like factor gene in erythroid cells. AB - The Sp/Kruppel-like factor (Sp/Klf) family is comprised of around 25 zinc finger transcription factors that recognize CACCC boxes and GC-rich elements. We have investigated basic Kruppel-like factor (Bklf/Klf3) and show that in erythroid tissues its expression is highly dependent on another family member, erythroid Kruppel-like factor (Eklf/Klf1). We observe that Bklf mRNA is significantly reduced in erythroid tissues from Eklf-null murine embryos. We find that Bklf is driven primarily by two promoters, a ubiquitously active GC-rich upstream promoter, 1a, and an erythroid downstream promoter, 1b. Transcripts from the two promoters encode identical proteins. Interestingly, both the ubiquitous and the erythroid promoter are dependent on Eklf in erythroid cells. Eklf also activates both promoters in transient assays. Experiments utilizing an inducible form of Eklf demonstrate activation of the endogenous Bklf gene in the presence of an inhibitor of protein synthesis. The kinetics of activation are also consistent with Bklf being a direct Eklf target. Chromatin immunoprecipitation assays confirm that Eklf associates with both Bklf promoters. Eklf is typically an activator of transcription, whereas Bklf is noted as a repressor. Our results support the hypothesis that feedback cross-regulation occurs within the Sp/Klf family in vivo. PMID- 17283066 TI - An acetylation/deacetylation-SUMOylation switch through a phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1 regulates transcriptional repression activity. AB - Tumor suppressor HIC1 (hypermethylated in cancer 1) is a gene that is essential for mammalian development, epigenetically silenced in many human tumors, and involved in a complex pathway regulating P53 tumor suppression activity. HIC1 encodes a sequence-specific transcriptional repressor containing five Kruppel like C(2)H(2) zinc fingers and an N-terminal BTB/POZ repression domain. Here, we show that endogenous HIC1 is SUMOylated in vivo on a phylogenetically conserved lysine, K314, located in the central region which is a second repression domain. K314R mutation does not influence HIC1 subnuclear localization but significantly reduces its transcriptional repression potential, as does the mutation of the other conserved residue in the psiKXE consensus, E316A, or the overexpression of the deSUMOylase SSP3/SENP2. Furthermore, HIC1 is acetylated in vitro by P300/CBP. Strikingly, the K314R mutant is less acetylated than wild-type HIC1, suggesting that this lysine is a target for both SUMOylation and acetylation. We further show that HIC1 transcriptional repression activity is positively controlled by two types of deacetylases, SIRT1 and HDAC4, which increase the deacetylation and SUMOylation, respectively, of K314. Knockdown of endogenous SIRT1 by the transfection of short interfering RNA causes a significant loss of HIC1 SUMOylation. Thus, this dual-deacetylase complex induces either a phosphorylation dependent acetylation-SUMOylation switch through a psiKXEXXSP motif, as previously shown for MEF2, or a phosphorylation-independent switch through a psiKXEP motif, as shown here for HIC1, since P317A mutation severely impairs HIC1 acetylation. Finally, our results demonstrate that HIC1 is a target of the class III deacetylase SIRT1 and identify a new posttranslational modification step in the P53-HIC1-SIRT1 regulatory loop. PMID- 17283067 TI - DNA-binding activity of the ERp57 C-terminal domain is related to a redox dependent conformational change. AB - ERp57, a member of the protein-disulfide isomerase family, although mainly localized in the endoplasmic reticulum is here shown to have a nuclear distribution. We previously showed the DNA-binding properties of ERp57, its association with the internal nuclear matrix, and identified the C-terminal region, containing the a' domain, as being directly involved in the DNA-binding activity. In this work, we demonstrate that its DNA-binding properties are strongly dependent on the redox state of the a' domain active site. Site-directed mutagenesis experiments on the first cysteine residue of the -CGHC-thioredoxin like active site lead to a mutant domain (C406S) lacking DNA-binding activity. Biochemical studies on the recombinant domain revealed a conformational change associated with the redox-dependent formation of a homodimer, having two disulfide bridges between the cysteine residues of two a' domain active sites. The formation of intermolecular disulfide bridges rather than intramolecular oxidation of active site cysteines is important to generate species with DNA binding properties. Thus, in the absence of any dedicated motif within the protein sequence, this structural rearrangement might be responsible for the DNA binding properties of the C-terminal domain. Moreover, NADH-dependent thioredoxin reductase is active on intermolecular disulfides of the a' domain, allowing the control of dimeric protein content as well as its DNA-binding activity. A similar behavior was also observed for whole ERp57. PMID- 17283068 TI - Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells. AB - The role of dihydroceramide desaturase as a key enzyme in the de novo pathway of ceramide generation was investigated in human neuroblastoma cells (SMS-KCNR). A novel assay using water-soluble analogs of dihydroceramide, dihydroceramidoids (D erythro-dhCCPS analogs), was used to measure desaturase activity in situ. Conversion of D-erythro-2-N-[12'-(1''-pyridinium)-dodecanoyl]-4,5 dihydrosphingosine bromide (C(12)-dhCCPS) to its 4,5-desaturated counterpart, D erythro-2-N-[12'-(1''-pyridinium)dodecanoyl]sphingosine bromide (C(12)-CCPS), was determined by liquid chromatography/mass spectrometry analysis. The validity of the assay was confirmed using C(8)-cyclopropenylceramide, a competitive inhibitor of dihydroceramide desaturase. A human homolog (DEGS-1) of the Drosophila melanogaster des-1 gene was recently identified and reported to have desaturase activity. Transfection of SMS-KCNR cells with small interfering RNA to DEGS-1 significantly blocked the conversion of C(12)-dhCCPS to C(12)-CCPS. The associated accumulation of endogenous dihydroceramides confirmed DEGS-1 as the main active dihydroceramide desaturase in these cells. The partial loss of DEGS-1 inhibited cell growth, with cell cycle arrest at G(0)/G(1). This was accompanied by a significant decrease in the amount of phosphorylated retinoblastoma protein. This hypophosphorylation was inhibited by tautomycin and not by okadaic acid, suggesting the involvement of protein phosphatase 1. Additionally, we found that treatment of SMS-KCNR cells with fenretinide inhibited desaturase activity in a dose-dependent manner. An increase in dihydroceramides (but not ceramides) paralleled this process as measured by liquid chromatography/mass spectrometry. There were no effects on the mRNA or protein levels of DEGS-1, suggesting that fenretinide acts at the post-translational level as an inhibitor of this enzyme. Tautomycin was also able to block the hypophosphorylation of the retinoblastoma protein observed upon fenretinide treatment. These findings suggest a novel biological function for dihydroceramides. PMID- 17283069 TI - Interaction between sterol regulatory element-binding proteins and liver receptor homolog-1 reciprocally suppresses their transcriptional activities. AB - In previous studies it was demonstrated that sterol regulatory element-binding proteins (SREBPs) are able to interact with one of the nuclear receptors, hepatocyte nuclear receptor (HNF)-4, and that this interaction regulates transcriptional activities of these proteins (Misawa, K., Horiba, T., Arimura, N., Hirano, Y., Inoue, J., Emoto, N., Shimano, H., Shimizu, M., and Sato, R. (2003) J. Biol. Chem. 278, 36176-36182; Yamamoto, T., Shimano, H., Nakagawa, Y., Ide, T., Yahagi, N., Matsuzaka, T., Nakakuki, M., Takahashi, A., Suzuki, H., Sone, H., Toyoshima, H., Sato, R., and Yamada, N. (2004) J. Biol. Chem. 279, 12027-12035). In an attempt to identify other nuclear receptor family members affecting the SREBP transcriptional activities, we found that the liver receptor homolog (LRH)-1 suppresses them. Several types of luciferase assays revealed that coexpression of these two proteins (LRH-1 and SREBP-1a, -1c, or -2) results in reciprocal inhibition of the transcriptional activity of each protein. It was confirmed that suppression in endogenous LRH-1 by small interference RNA stimulates the mRNA levels of certain SREBP target genes and that elevation in active SREBPs in the nucleus in response to cholesterol depletion suppresses the LRH-1 activity. In vitro/in vivo glutathione S-transferase pulldown experiments demonstrated that the basic helix-loop-helix-leucine zipper domain in SREBP-2 binds to the ligand-binding domain in LRH-1. Furthermore, we found that SREBP-2 interferes with the recruitment of a coactivator of LRH-1, the peroxisome proliferator-activated receptor gamma coactivator-1alpha, thereby leading to the inhibition of the LRH-1 transcriptional activity. These results clearly indicate that the interaction between SREBPs and LRH-1 exerts a suppressive influence on their target gene expression responsible for cholesterol and bile acid metabolism. PMID- 17283070 TI - Competition between Ski and CREB-binding protein for binding to Smad proteins in transforming growth factor-beta signaling. AB - The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational studies. Here, we show that Ski-(16-192) interacted directly with a homotrimer of receptor regulated Smad protein (R-Smad), e.g. Smad2 or Smad3, to form a hexamer; Ski-(16 192) interacted with an R-Smad.Smad4 heterotrimer to form a pentamer. CBP-(1941 1992) was also found to interact directly with an R-Smad homotrimer to form a hexamer and with an R-Smad.Smad4 heterotrimer to form a pentamer. Moreover, these domains of Ski and CBP competed with each other for binding to Smad3. Our mutational studies revealed that domains of Ski and CBP interacted with Smad3 at a portion of the binding surface of the Smad anchor for receptor activation. Our results suggest that Ski negatively regulates TGF-beta signaling by replacing CBP in R-Smad complexes. Our working model suggests that Smad protein activity is delicately balanced by Ski and CBP in the TGF-beta pathway. PMID- 17283071 TI - Choline redistribution during adaptation to choline deprivation. AB - Choline is an important nutrient for mammals. Choline can also be generated by the catabolism of phosphatidylcholine synthesized in the liver by the methylation of phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase (PEMT). Complete choline deprivation is achieved by feeding Pemt(-)(/)(-) mice a choline-deficient diet and is lethal due to liver failure. Mice that lack both PEMT and MDR2 (multiple drug-resistant protein 2) successfully adapt to choline deprivation via hepatic choline recycling. We now report another mechanism involved in this adaptation, choline redistribution. Normal levels of choline containing metabolites were maintained in the brains of choline-deficient Mdr2( )(/)(-)/Pemt(-)(/)(-) mice for 90 days despite continued choline consumption via oxidation. Choline oxidase activity had not been previously detected in the brain. Plasma levels of choline were also maintained for 90 days, whereas plasma phosphatidylcholine levels decreased by >60%. The injection of [(3)H]choline into Mdr2(-)(/)(-)/Pemt(-)(/)(-) mice revealed a redistribution of choline among tissues. Although CD-Pemt(-)(/)(-) mice failed to adapt to choline deprivation, choline redistribution was also initiated in these mice. The data suggest that adaptation to choline deprivation is not restricted to liver via choline recycling but also occurs in the whole animal via choline redistribution. PMID- 17283072 TI - Structural insights into corepressor recognition by antagonist-bound estrogen receptors. AB - Direct recruitment of transcriptional corepressors to estrogen receptors (ER) is thought to contribute to the tissue-specific effects of clinically important ER antagonists. Here, we present the crystal structures of two affinity-selected peptides in complex with antagonist-bound ERalpha ligand-binding domain. Both peptides adopt helical conformations, bind along the activation function 2 coregulator interaction surface, and mimic corepressor (CoRNR) sequence motif binding. Peptide binding is weak in a wild-type context but significantly enhanced by removal of ER helix 12. This region contains a previously unrecognized CoRNR motif that is able to compete with corepressors for binding to activation function 2, thereby providing a structural explanation for the poor ability of ER to directly interact with classical corepressors. Furthermore, the ability of other sequence motifs to mimic corepressor binding raises the possibility that coregulators do not necessarily require CoRNR motifs for direct recruitment to antagonist-bound ER. PMID- 17283073 TI - A cell-permeable fusion toxin as a tool to study the consequences of actin-ADP ribosylation caused by the salmonella enterica virulence factor SpvB in intact cells. AB - The virulence factor SpvB is a crucial component for the intracellular growth and infection process of Salmonella enterica. The SpvB protein mediates the ADP ribosylation of actin in infected cells and is assumed to be delivered directly from the engulfed bacteria into the host cell cytosol. Here we used the binary Clostridium botulinum C2 toxin as a transport system for the catalytic domain of SpvB (C/SpvB) into the host cell cytosol. A recombinant fusion toxin composed of the enzymatically inactive N-terminal domain of C. botulinum C2 toxin (C2IN) and C/SpvB was cloned, expressed, and characterized in vitro and in intact cells. When added together with C2II, the C2IN-C/SpvB fusion toxin was efficiently delivered into the host cell cytosol and ADP-ribosylated actin in various cell lines. The cellular uptake of the fusion toxin requires translocation from acidic endosomes into the cytosol and is facilitated by Hsp90. The N- and C-terminal domains of SpvB are linked by 7 proline residues. To elucidate the function of this proline region, fusion toxins containing none, 5, 7, and 9 proline residues were constructed and analyzed. The existence of the proline residues was essential for the translocation of the fusion toxins into host cell cytosol and thereby determined their cytopathic efficiency. No differences concerning the mode of action of the C2IN-C/SpvB fusion toxin and the C2 toxin were obvious as both toxins induced depolymerization of actin filaments, resulting in cell rounding. The acute cellular responses following ADP-ribosylation of actin did not immediately induce cell death of J774.A1 macrophage-like cells. PMID- 17283074 TI - Characterization of a novel tripartite nuclear localization sequence in the EGFR family. AB - Aberrant expression of epidermal growth factor receptor (EGFR) is present in many human tumors. Several reports have shown that EGFR is translocated into the nucleus during liver regeneration and in several types of cells and tissues such as placenta and thyroid. Nuclear EGFR is associated with transcription, DNA synthesis, and DNA repair activity and serves as a prognostic marker in breast carcinoma and oropharyngeal squamous cell cancer. However, the nuclear localization sequence (NLS) of EGFR has not been extensively examined. In this study, we have shown that the juxtamembrane region of EGFR harbors a putative NLS with three clusters of basic amino acids (RRRHIVRKRTLRR (amino acids 645-657)) that mediates the nuclear localization of EGFR. We found that this newly characterized tripartite NLS is conserved among the EGFR family members (EGFR, ErbB2, ErbB3, and ErbB4) and is able to move each to the nucleus. Further, this tripartite NLS could also mediate the nuclear localization of other known cytoplasmic proteins such as pyruvate kinase. We have demonstrated that mutating one of the three basic amino acid clusters (R or K --> A) leads to significant impairment of the nuclear localization of EGFR and that of a green fluorescent protein-pyruvate kinase-NLS reporter protein. Our results show that this tripartite NLS is distinct from the traditional mono- and bipartite NLS and reveal a mechanism that could account for the nuclear localization of membrane receptors. PMID- 17283075 TI - Use of a cAMP BRET sensor to characterize a novel regulation of cAMP by the sphingosine 1-phosphate/G13 pathway. AB - Regulation of intracellular cyclic adenosine 3 ',5 '-monophosphate (cAMP) is integral in mediating cell growth, cell differentiation, and immune responses in hematopoietic cells. To facilitate studies of cAMP regulation we developed a BRET (bioluminescence resonance energy transfer) sensor for cAMP, CAMYEL (cAMP sensor using YFP-Epac-RLuc), which can quantitatively and rapidly monitor intracellular concentrations of cAMP in vivo. This sensor was used to characterize three distinct pathways for modulation of cAMP synthesis stimulated by presumed G(s) dependent receptors for isoproterenol and prostaglandin E(2). Whereas two ligands, uridine 5 '-diphosphate and complement C5a, appear to use known mechanisms for augmentation of cAMP via G(q)/calcium and G(i), the action of sphingosine 1-phosphate (S1P) is novel. In these cells, S1P, a biologically active lysophospholipid, greatly enhances increases in intracellular cAMP triggered by the ligands for G(s)-coupled receptors while having only a minimal effect by itself. The enhancement of cAMP by S1P is resistant to pertussis toxin and independent of intracellular calcium. Studies with RNAi and chemical perturbations demonstrate that the effect of S1P is mediated by the S1P(2) receptor and the heterotrimeric G(13) protein. Thus in these macrophage cells, all four major classes of G proteins can regulate intracellular cAMP. PMID- 17283076 TI - Phosphorylation of a Wiscott-Aldrich syndrome protein-associated signal complex is critical in osteoclast bone resorption. AB - The activities of different kinases have been correlated to the phosphorylation of Wiscott-Aldrich syndrome protein (WASP) by studies in multiple cell systems. The purpose of this study was to elucidate the regulatory mechanisms involved in WASP phosphorylation and the resulting sealing ring formation in osteoclasts. The phosphorylation state of WASP and WASP-interacting proteins was determined in osteoclasts treated with osteopontin or expressing either constitutively active or kinase-defective Src by adenovirus-mediated delivery. In vitro kinase analysis of WASP immunoprecipitates exhibited phosphorylation of c-Src, PYK2, WASP, protein-tyrosine phosphatase (PTP)-PEST, and Pro-Ser-Thr phosphatase-interacting protein (PSTPIP). Phosphorylation of these proteins was increased in osteopontin treated and constitutively active Src-expressing osteoclasts. Pulldown analysis with glutathione S-transferase-fused proline-rich regions of PTP-PEST revealed coprecipitation of WASP, PYK2, c-Src, and PSTPIP proteins with the N-terminal region (amino acids 294-497) of PTP-PEST. Similarly, interaction of the same signaling proteins, as well as PTP-PEST, was observed with glutathione S transferase-fused proline-rich regions of WASP. Furthermore, osteopontin stimulation or constitutively active Src expression resulted in serine phosphorylation and inhibition of WASP-associated PTP-PEST. The inhibition of PTP PEST was accompanied by an increase in tyrosine phosphorylation of WASP and other associated signaling proteins. Experiments with an inhibitor to phosphatase and small interference RNA to PTP-PEST confirmed the involvement of PTP-PEST in sealing ring formation and bone resorption. WASP, which is identified in the sealing ring of resorbing osteoclasts, also demonstrates colocalization with c Src, PYK2, PSTPIP, and PTP-PEST in immunostaining analyses. Our findings suggest that both tyrosine kinase(s) and the tyrosine phosphatase PTP-PEST coordinate the formation of the sealing ring and thus the bone-resorbing function of osteoclasts. PMID- 17283077 TI - The dynamics of the rapsyn scaffolding protein at individual acetylcholine receptor clusters. AB - Rapsyn, a cytoplasmic receptor-associated protein, is required for the clustering of acetylcholine receptors (AChRs). Although AChR dynamics have been extensively studied, little is known about the dynamics of rapsyn. Here, we used a rapsyn green fluorescent protein (GFP) fusion protein and quantitative fluorescent imaging to study the dynamics of rapsyn in transfected C2C12 myotubes. First, we found that rapsyn-GFP expression at clusters did not alter AChR aggregation, function, or turnover. Quantification of rapsyn immunofluorescence indicated that the expression of rapsyn-GFP proteins at clusters does not increase the overall rapsyn density compared with untransfected myotube clusters. Using time lapse imaging and fluorescence recovery after photobleaching, we demonstrated that the recovery of rapsyn-GFP fluorescence at clusters was very fast, with a halftime of about approximately 1.5 h (approximately 3 times faster than AChRs). Inhibition of protein kinase C significantly altered receptor insertion, but it had no effect on rapsyn insertion. When cells were treated with the broad spectrum kinase inhibitor staurosporine, receptor insertion was decreased even further. However, inhibition of protein kinase A had no effect on insertion of either rapsyn or receptors. Finally, when cells were treated with neural agrin, rapsyn and AChRs were both directed away from preexisting clusters and accumulated together in new small clusters. These results demonstrate the remarkable dynamism of rapsyn, which may underlie the stability and maintenance of the postsynaptic scaffold and suggest that the insertion of different postsynaptic proteins may be operating independently. PMID- 17283078 TI - Transcriptional repression of matrix metalloproteinase gene expression by the orphan nuclear receptor NURR1 in cartilage. AB - The NR4A orphan receptors (Nur77, NURR1, and NOR-1) are emerging as key regulators of cytokine and growth factor action in chronic inflammatory diseases. In this study, we address the role of these receptors in cartilage homeostasis during inflammatory joint disease. We document for the first time expression of the NR4A receptors in osteoarthritic cartilage. Relative to Nur77 and NOR-1, NURR1 is expressed at the highest level and correlates with cyclooxygenase-2 levels in cartilage. Consistent with this observation, cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)) rapidly and potently induces NURR1 expression in chondrocytes, suggesting that this receptor may regulate PGE(2)-mediated processes in cartilage. We demonstrate that PGE(2) represses interleukin-1beta induced matrix metalloproteinase (MMP)-1 and that transient overexpression of NURR1 is sufficient to antagonize expression of this gene. Furthermore, MMP-1 promoter activity is potently suppressed by NURR1, resulting in a significant reduction in endogenous MMP-1 mRNA and secreted pro-MMP-1 protein. In addition, NURR1 selectively antagonizes cytokine-induced MMP-3 and -9 expression with minimal effects on MMP-2 and -13 and tissue inhibitor of matrix metalloproteinases-1 and -2. To explore the molecular mechanisms of NURR1 transrepression, we reveal that this receptor targets a critical region of the MMP-1 promoter (-1772 to -1546 bp) and that repression does not require consensus binding sites for NURR1. We confirm that NURR1 targets a 40-bp promoter sequence that is also positively regulated by ETS transcription factors. Finally, functional studies indicate that transcriptional antagonism exists between NURR1 and ETS1 on the MMP-1 promoter. We propose a protective function for NURR1 in cartilage homeostasis by selectively repressing MMP gene expression during inflammation. PMID- 17283079 TI - Functional interaction between the transcription factor Kruppel-like factor 5 and poly(ADP-ribose) polymerase-1 in cardiovascular apoptosis. AB - Kruppel-like factor 5 (KLF5) is a transcription factor important in regulation of the cardiovascular response to external stress. KLF5 regulates pathological cell growth, and its acetylation is important for this effect. Its mechanisms of action, however, are still unclear. Analysis in KLF5-deficient mice showed that KLF5 confers apoptotic resistance in vascular lesions. Mechanistic analysis further showed that it specifically interacts with poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme important in DNA repair and apoptosis. KLF5 interacted with a proteolytic fragment of PARP-1, and acetylation of KLF5 under apoptotic conditions increased their affinity. Moreover, KLF5 wild-type (but not a non acetylatable point mutant) inhibited apoptosis as induced by the PARP-1 fragment. Collectively, we have found that KLF5 regulates apoptosis and targets PARP-1, and further, for acetylation to regulate these effects. Our findings thus implicate functional interaction between the transcription factor KLF5 and PARP-1 in cardiovascular apoptosis. PMID- 17283080 TI - A Pentatricopeptide repeat protein is required for RNA processing of clpP Pre mRNA in moss chloroplasts. AB - Pentatricopeptide repeat (PPR) proteins are encoded by the nuclear genome as a large gene family in land plants. PPR proteins play essential roles in organelle related functions, mostly in RNA-processing steps in plastids and mitochondria. In the moss Physcomitrella patens, there is also a large gene family, but the moss PPR proteins are likely to be divergent from those of higher plants. To investigate the function of plastid PPR proteins, we have generated and characterized a PPR protein gene disruptant of P. patens. The PPR531-11-disrupted mosses displayed abnormal phenotypic characteristics, such as a significantly smaller protonemal colony, different chloroplast morphology, and incomplete thylakoid membrane formation. In addition, the quantum yield of photosystem II was reduced in the disrupted mosses. To further investigate whether disruption of the PPR531-11 gene affects chloroplast gene expression, we performed Northern blot and reverse transcription polymerase chain reaction analyses. These analyses revealed that PPR531-11 has a role in intergenic RNA cleavage between clpP and 5' rps12 and in the splicing of clpP pre-mRNA. Western blot analysis showed that disruption of PPR531-11 resulted in a reduced level of ClpP, photosystem II reaction center protein D1, and the stromal enzyme, ribulose-bisphosphate carboxylase/oxygenase. These reductions might result in the severely retarded growth of the protonemal colony. Taken together, we propose a model where PPR531 11 function affects the steady-state level of ClpP, which regulates the formation and maintenance of thylakoid membranes in chloroplasts. This is the first evidence of a PPR protein controlling the protein expression level of ClpP. PMID- 17283081 TI - STIM1 knockdown reveals that store-operated Ca2+ channels located close to sarco/endoplasmic Ca2+ ATPases (SERCA) pumps silently refill the endoplasmic reticulum. AB - Stromal interaction molecule (STIM) proteins are putative ER Ca2+ sensors that recruit and activate store-operated Ca2+ (SOC) channels at the plasma membrane, a process triggered by the Ca2+ depletion of the endoplasmic reticulum (ER). To test whether STIM1 is required for ER refilling, we used RNA interference and measured Ca2+ signals in the cytosol, the ER, and the mitochondria of HeLa cells. Knockdown of STIM1 (mRNA levels, 73%) reduced SOC entry by 73% when sarco/endoplasmic Ca2+ ATPases (SERCA) were inhibited by thapsigargin but did not prevent Ca2+ stores refilling when cells were stimulated by physiological agonists. Stores could be fully refilled by increasing the external Ca2+ concentration above physiological values, but no cytosolic Ca2+ signals were detected during store refilling even at very high Ca2+ concentrations. [Ca2+](ER) measurements revealed that the basal activity of SERCA was not affected in STIM1 knockdown cells and that [Ca2+](ER) levels were restored within 2 min in physiological saline following store depletion. Mitochondrial inhibitors reduced ER refilling in wild-type but not in STIM1 knockdown cells, indicating that ER refilling does not require functional mitochondria at low STIM1 levels. Our data show that ER refilling is largely preserved at reduced STIM1 levels, despite a drastic reduction of store-operated Ca2+ entry, because Ca2+ ions are directly transferred from SOC channels to SERCA. These findings are consistent with the formation of microdomains containing not only SOC channels on the plasma membrane and STIM proteins on the ER but also SERCA pumps and mitochondria to refill the ER without perturbing the cytosol. PMID- 17283082 TI - A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome. AB - The proteasome usually completely degrades its target proteins, but it can also degrade a handful of proteins in a limited and site-specific manner. The molecular mechanism for such limited degradation is unknown. The repressor forms of Gli2 and Gli3 transcription factors are generated from their full-length proteins through limited proteasome-mediated protein degradation. In this study, we have taken advantage of the fact that Gli3 is efficiently processed, whereas Gli2 is not, and identified a region of approximately 200 residues in their C termini that determine differential processing of the two proteins. This region, named processing determinant domain, functions as a signal for protein processing in the context of not only Gli2 and Gli3 protein sequences but also a heterologous hybrid protein, which would otherwise be completely degraded by the proteasome. Thus, the processing determinant domain constitutes a novel domain that functions independently. Our findings explain, at the molecular level, why Gli2 and Gli3 are differentially processed and, more importantly, may help understand a probably general mechanism by which the proteasome degrades some of its target proteins partially rather than completely. PMID- 17283083 TI - Molecular factors and biochemical pathways induced by febrile temperature in intraerythrocytic Plasmodium falciparum parasites. AB - Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in asexual-stage Plasmodium falciparum parasite cultures incubated at 37 degrees C and 41 degrees C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host). Elevated temperature had a profound influence on expression of individual genes; 336 of approximately 5,300 genes (6.3% of the genome) had altered expression profiles. Of these, 163 genes (49%) were upregulated by twofold or greater, and 173 genes (51%) were downregulated by twofold or greater. In-depth sensitive sequence profile analysis revealed that febrile temperature induced responses caused significant alterations in the major parasite biologic networks and pathways and that these changes are well coordinated and intricately linked. One of the most notable transcriptional changes occurs in genes encoding proteins containing the predicted Pexel motifs that are exported into the host cytoplasm or inserted into the host cell membrane and are likely to be associated with erythrocyte remodeling and parasite sequestration functions. Using our sensitive computational analysis, we were also able to assign biochemical or biologic functional predictions for at least 100 distinct genes previously annotated as "hypothetical." We find that cultivation of P. falciparum parasites at 41 degrees C leads to parasite death in a time-dependent manner. The presence of the "crisis forms" and the terminal deoxynucleotidyltransferase-mediated dUTP biotin nick end labeling-positive parasites following heat treatment strongly support the notion that an apoptosis-like cell death mechanism might be induced in response to febrile temperatures. These studies enhance the possibility of designing vaccines and drugs on the basis of disruption in molecules and pathways of parasite survival and virulence activated in response to febrile temperatures. PMID- 17283084 TI - The SAG1 Toxoplasma gondii surface protein is not required for acute ocular toxoplasmosis in mice. AB - The SAG1 Toxoplasma gondii surface protein stimulates acute ileitis. To determine whether SAG1 is also important in the eye, wild-type or SAG1 knockout parasites were injected intravitreally into mice. No differences in retinal damage or parasite growth were observed, indicating that unlike the case for the intestine, factors besides SAG1 are important for retinal damage. PMID- 17283085 TI - Immunoglobulin G antibody reactivity to a group A Plasmodium falciparum erythrocyte membrane protein 1 and protection from P. falciparum malaria. AB - Variant surface antigens (VSA) on the surface of Plasmodium falciparum-infected red blood cells play a major role in the pathogenesis of malaria and are key targets for acquired immunity. The best-characterized VSA belong to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. In areas where P. falciparum is endemic, parasites causing severe malaria and malaria in young children with limited immunity tend to express semiconserved PfEMP1 molecules encoded by group A var genes. Here we investigated antibody responses of Tanzanians who were 0 to 19 years old to PF11_0008, a group A PfEMP1. PF11_0008 has previously been found to be highly transcribed in a nonimmune Dutch volunteer experimentally infected with NF54 parasites. A high proportion of the Tanzanian donors had antibodies against recombinant PF11_0008 domains, and in children who were 4 to 9 years old the presence of antibodies to the PF11_0008 CIDR2beta domain was associated with reduced numbers of malaria episodes. These results indicate that homologues of PF11_0008 are present in P. falciparum field isolates and suggest that PF11_0008 CIDR2beta-reactive antibodies might be involved in protection against malaria episodes. PMID- 17283087 TI - The genome of non-O1 Vibrio cholerae NRT36S demonstrates the presence of pathogenic mechanisms that are distinct from those of O1 Vibrio cholerae. AB - Vibrio cholerae NRT36S is a non-cholera toxin-producing, non-O1 strain that causes diarrhea in volunteers. The genome of NRT36S was sequenced to create a draft containing 174 contigs plus the superintegron region. Our analysis of the draft genome revealed several putative toxin genes and colonization factors. Besides confirming the existence of nonagglutinable heat-stable toxin, we also identified the genes for a type three secretion system, a putative exotoxin, two different RTX toxins, and four pilus systems. PMID- 17283086 TI - Evidence for widespread epithelial damage and coincident production of monocyte chemotactic protein 1 in a murine model of intestinal ricin intoxication. AB - The development of small-animal models is necessary to understand host responses and immunity to emerging infectious diseases and potential bioterrorism agents. In this report we have characterized a murine model of intestinal ricin intoxication. Ricin administered intragastrically (i.g.) to BALB/c mice at doses ranging from 1 to 10 mg/kg of body weight induced dose-dependent morphological changes in the proximal small intestine (i.e., duodenum), including widespread villus atrophy and epithelial damage. Coincident with epithelial damage was a localized increase in monocyte chemotactic protein 1, a chemokine known to be associated with inflammation of the intestinal mucosa. Immunity to intestinal ricin intoxication was achieved by immunizing mice i.g. with ricin toxoid and correlated with elevated levels of antitoxin mucosal immunoglobulin A (IgA) and serum IgG antibodies. We expect that this model will serve as a valuable tool in identifying the inflammatory pathways and protective immune responses that are elicited in the intestinal mucosa following ricin exposure and will prove useful in the evaluation of antitoxin vaccines and therapeutics. PMID- 17283088 TI - Cloning, expression, and characterization of the superantigen streptococcal pyrogenic exotoxin G from Streptococcus dysgalactiae. AB - We identified seven novel variants of streptococcal pyrogenic exotoxin G (SPEGG), a superantigen, in Streptococcus dysgalactiae subsp. dysgalactiae or equisimilis isolates from clinical cases of infection in humans and animals. Phylogenetic analysis of the SPEGG variants indicated two clades in the dendrogram: one composed of variants derived from the bacteria isolated from the humans and the other composed of variants from the bacteria isolated from the animals. Bovine peripheral blood mononuclear cells (PBMCs) were stimulated effectively by recombinant SPEGGs (rSPEGGs) expressed in Escherichia coli, while human PBMCs were not stimulated well by any of the rSPEGGs tested. SPEGGs selectively stimulated bovine T cells bearing Vbeta1,10 and Vbeta4. Bovine serum showed reactivity to the rSPEGG proteins. These results indicated that SPEGGs have properties as superantigens, and it is likely that SPEGGs play a pathogenic role in animals. PMID- 17283091 TI - In vivo adaptation of the Wayne model of latent tuberculosis. AB - Cultures of Mycobacterium tuberculosis grown under oxygen depletion conditions enter into a state of nonreplicating persistence that may reflect a physiologically latent state. When these cultures were harvested and injected intranasally into mice, no bacteria could be recovered from the lungs for about 3 weeks, but after that evidence of regrowth was observed. Preimmunization of mice with a panel of selected vaccine candidates slowed or prevented this event. This simple model has potential for identifying vaccines targeting latent tuberculosis. PMID- 17283090 TI - A caspase-independent pathway mediates macrophage cell death in response to Mycobacterium tuberculosis infection. AB - Macrophages can undergo apoptosis after infection with Mycobacterium tuberculosis. This macrophage response deprives the bacillus of its niche cell and supports the host response through better antigen presentation. The intracellular pathways of apoptosis that elaborate this macrophage response are not well understood. To address this issue, we investigated the contribution of various apoptosis pathways to M. tuberculosis-induced macrophage cell death. We found that macrophages die in a caspase-independent manner after infection with M. tuberculosis (at multiplicities of infection ranging from 1 to 20). There was evidence for the involvement of both the mitochondria (cleavage of Bid) and the lysosomes (cathepsin-mediated DNA fragmentation) in this cell death pathway. Dying macrophages displayed several features typical of apoptosis, including DNA fragmentation, nuclear condensation, and exposure of phosphatidylserine on the plasma membrane. However, nuclear fragmentation was not observed, which suggests that M. tuberculosis-induced cell death differs in some respects from classical apoptosis. This novel mechanism of cell death was blocked by serine protease inhibitors. A better understanding of this protective macrophage response may direct new vaccine and treatment options. PMID- 17283089 TI - Resistance to Pseudomonas aeruginosa chronic lung infection requires cystic fibrosis transmembrane conductance regulator-modulated interleukin-1 (IL-1) release and signaling through the IL-1 receptor. AB - Innate immunity is critical for clearing Pseudomonas aeruginosa from the lungs. In response to P. aeruginosa infection, a central transcriptional regulator of innate immunity-NF-kappaB-is translocated within 15 min to the nuclei of respiratory epithelial cells expressing wild-type (WT) cystic fibrosis (CF) transmembrane conductance regulator (CFTR). P. aeruginosa clearance from lungs is impaired in CF, and rapid NF-kappaB nuclear translocation is defective in cells with mutant or missing CFTR. We used WT and mutant P. aeruginosa and strains of transgenic mice lacking molecules involved in innate immunity to identify additional mediators required for P. aeruginosa-induced rapid NF-kappaB nuclear translocation in lung epithelia. We found neither Toll-like receptor 2 (TLR2) nor TLR4 nor TLR5 were required for this response. However, both MyD88-deficient mice and interleukin-1 receptor (IL-1R)-deficient mice failed to rapidly translocate NF-kappaB to the nuclei of respiratory epithelial cells in response to P. aeruginosa. Cultured human bronchial epithelial cells rapidly released IL-1beta in response to P. aeruginosa; this process was maximized by expression of WT-CFTR and dramatically muted in cells with DeltaF508-CFTR. The IL-1R antagonist blocked P. aeruginosa-induced NF-kappaB nuclear translocation. Oral inoculation via drinking water of IL-1R knockout mice resulted in higher rates of lung colonization and elevated P. aeruginosa-specific antibody titers in a manner analogous to that of CFTR-deficient mice. Overall, rapid IL-1 release and signaling through IL-1R represent key steps in the innate immune response to P. aeruginosa infection, and this process is deficient in cells lacking functional CFTR. PMID- 17283092 TI - Coinfection with Schistosoma mansoni reactivates viremia in rhesus macaques with chronic simian-human immunodeficiency virus clade C infection. AB - We tested the hypothesis that helminth parasite coinfection would intensify viremia and accelerate disease progression in monkeys chronically infected with an R5 simian-human immunodeficiency virus (SHIV) encoding a human immunodeficiency virus type 1 (HIV-1) clade C envelope. Fifteen rhesus monkeys with stable SHIV-1157ip infection were enrolled into a prospective, randomized trial. These seropositive animals had undetectable viral RNA and no signs of immunodeficiency. Seven animals served as virus-only controls; eight animals were exposed to Schistosoma mansoni cercariae. From week 5 after parasite exposure onward, coinfected animals shed eggs in their feces, developed eosinophilia, and had significantly higher mRNA expression of the T-helper type 2 cytokine interleukin-4 (P = 0.001) than animals without schistosomiasis. Compared to virus only controls, viral replication was significantly increased in coinfected monkeys (P = 0.012), and the percentage of their CD4(+) CD29(+) memory cells decreased over time (P = 0.05). Thus, S. mansoni coinfection significantly increased viral replication and induced T-cell subset alterations in monkeys with chronic SHIV clade C infection. PMID- 17283093 TI - Mice lacking CD21 and CD35 proteins mount effective immune responses against Borrelia burgdorferi infection. AB - CD21/35(-/-) mice, deficient in CD21 and CD35 (complement receptors 2 and 1, respectively), were infected with Borrelia burgdorferi to assess the role of these receptors in a chronic bacterial infection. Although CD21/35(-/-) mice on both C57BL/6 and BALB/c backgrounds produced less B. burgdorferi-specific antibodies than did wild-type mice, spirochete levels and arthritis severity were similar. PMID- 17283095 TI - Effect of farnesol on a mouse model of systemic candidiasis, determined by use of a DPP3 knockout mutant of Candida albicans. AB - This work extends our previous observation that the fungus Candida albicans secretes micromolar levels of farnesol and that accumulation of farnesol in vitro prevents the yeast-to-mycelium conversion in a quorum-sensing manner. What does farnesol do in vivo? The purpose of this study was to determine the role of farnesol during infection with a well-established mouse model of systemic candidiasis with C. albicans A72 administered by tail vein injection. This question was addressed by altering both endogenous and exogenous farnesol. For endogenous farnesol, we created a knockout mutation in DPP3, the gene encoding a phosphatase which converts farnesyl pyrophosphate to farnesol. This mutant (KWN2) produced six times less farnesol and was ca. 4.2 times less pathogenic than its SN152 parent. The strain with DPP3 reconstituted (KWN4) regained both its farnesol production levels and pathogenicity. These mutants (KWN1 to KWN4) retained their full dimorphic capability. With regard to exogenous farnesol, farnesol was administered either intraperitoneally (i.p.) or orally in the drinking water. Mice receiving C. albicans intravenously and farnesol (20 mM) orally had enhanced mortality (P < 0.03). Similarly, mice (n = 40) injected with 1.0 ml of 20 mM farnesol i.p. had enhanced mortality (P < 0.03), and the onset of mortality was 30 h sooner than for mice which received a control injection without farnesol. The effect of i.p. farnesol was more pronounced (P < 0.04) when mice were inoculated with a sublethal dose of C. albicans. These mice started to die 4 days earlier, and the percent survival on day 6 postinoculation (p.i.) was five times lower than for mice receiving C. albicans with control i.p. injections. In all experiments, mice administered farnesol alone or Tween 80 alone remained normal throughout a 14-day observation period. Finally, beginning at 12 h p.i., higher numbers of C. albicans cells were detected in kidneys from mice receiving i.p. farnesol than in those from mice receiving control i.p. injections. Thus, reduced endogenous farnesol decreased virulence, while providing exogenous farnesol increased virulence. Taken together, these data suggest that farnesol may play a role in disease pathogenesis, either directly or indirectly, and thus may represent a newly identified virulence factor. PMID- 17283094 TI - Immunity to microbes: lessons from primary immunodeficiencies. PMID- 17283097 TI - Induction of human beta-defensin 2 by the probiotic Escherichia coli Nissle 1917 is mediated through flagellin. AB - Human beta-defensin 2 (hBD-2) is an inducible antimicrobial peptide synthesized by the epithelium to counteract bacterial adherence and invasion. Proinflammatory cytokines, as well as certain bacterial strains, have been identified as potent endogenous inducers. Recently, we have found that hBD-2 induction by probiotic Escherichia coli Nissle 1917 was mediated through NF-kappaB- and AP-1-dependent pathways. The aim of the present study was to identify the responsible bacterial factor. E. coli Nissle 1917 culture supernatant was found to be more potent than the pellet, indicating a soluble or shed factor. Chemical analysis demonstrated the factor to be heat resistant and proteinase digestible. Several E. coli Nissle 1917 deletion mutants were constructed and tested for their ability to induce hBD 2 expression in Caco-2 cells. Deletion mutants for flagellin specifically exhibited an impaired immunostimulatory capacity. Reinsertion of the flagellin gene restored the induction capacity to normal levels. Isolated flagellin from E. coli Nissle 1917 and from Salmonella enterica serovar Enteritidis induced hBD-2 mRNA significantly in contrast to the flagellin of the apathogenic E. coli strain ATCC 25922. H1 flagellin antiserum abrogated hBD-2 expression induced by flagellin as well as E. coli Nissle 1917 supernatant, confirming that flagellin is the major stimulatory factor of E. coli Nissle 1917. PMID- 17283096 TI - Trypanosoma cruzi infection induces differential modulation of costimulatory molecules and cytokines by monocytes and T cells from patients with indeterminate and cardiac Chagas' disease. AB - Interactions between macrophages and lymphocytes through costimulatory molecules and cytokines are essential for mounting an efficient immune response and controlling its pathogenic potential. Here we demonstrate the immunomodulatory capacity of Trypanosoma cruzi, the causative agent of Chagas' disease, through its ability to induce differential expression of costimulatory molecules and cytokines by monocytes and T cells. Costimulatory molecule and cytokine modulation was evaluated using cells from noninfected individuals and from patients with the asymptomatic indeterminate form and those with the severe cardiac clinical form of Chagas' disease. Our results show that while exposure of monocytes to live T. cruzi leads to an increase in the frequency of CD80(+) monocytes in all groups, it decreases both the frequency and intensity of CD86 expression by monocytes from patients with the cardiac form but not from those with the indeterminate form. Conversely, exposure of lymphocytes to monocytes infected with T. cruzi increased the surface expression of cytotoxic-T-lymphocyte associated antigen 4 (CTLA-4) by T cells from indeterminate but not from cardiac patients, compared to that from control patients. These data suggest that T. cruzi induces a potentially down-regulatory environment in indeterminate subjects, which is associated with higher CD80 and CTLA-4 expression. To test the functional importance of this modulation, we evaluated the expression of cytokines after in vitro infection. Although exposure of lymphocytes to parasite infected monocytes induced high expression of inflammatory and anti-inflammatory cytokines by T cells in all groups, indeterminate patients displayed a higher ratio of monocytes expressing interleukin 10 than tumor necrosis factor alpha following infection than did controls. These data show the ability of T. cruzi to actively change the expression of costimulatory molecules and cytokines, suggesting molecular mechanisms for the differential clinical evolution of human Chagas' disease. PMID- 17283098 TI - Evidence of immunostimulating lipoprotein existing in the natural lipoteichoic acid fraction. AB - Lipoteichoic acid (LTA) is a cell surface glycoconjugate of gram-positive bacteria and is reported to activate the innate immune system. We previously reported that purified LTA obtained from Enterococcus hirae has no immunostimulating activity, but a subfraction (Eh-AF) in an LTA fraction possesses activity. In this study, we established a mouse monoclonal antibody neutralizing the activity of Eh-AF and investigated its inhibitory effects. Monoclonal antibody (MAbEh1) was established by the immunization of BALB/c mice with Eh-AF, followed by hybridoma screening based on its inhibitory effect for the production of interleukin-6 (IL-6) induced by Eh-AF. MAbEh1 neutralized the production of IL-6 by LTA fraction from not only E. hirae but also Staphylococcus aureus, while it failed to block that of lipopolysaccharide, suggesting that the antibody recognized a common active structure(s) in LTA fractions. Synthetic glycolipids in these LTAs did not induce cytokine production, at least in our system. Interestingly, the antibody was found to inhibit the activity of immunostimulating synthetic lipopeptides, Pam(3)CSK(4) and FSL-1. These results suggest that MAbEh1 neutralizes the activity of lipoprotein-like compounds which is responsible for the activity of the LTA fraction of E. hirae and S. aureus. PMID- 17283100 TI - Carboxypeptidases B of Anopheles gambiae as targets for a Plasmodium falciparum transmission-blocking vaccine. AB - Anopheles gambiae is the major African vector of Plasmodium falciparum, the most deadly species of human malaria parasite and the most prevalent in Africa. Several strategies are being developed to limit the global impact of malaria via reducing transmission rates, among which are transmission-blocking vaccines (TBVs), which induce in the vertebrate host the production of antibodies that inhibit parasite development in the mosquito midgut. So far, the most promising components of a TBV are parasite-derived antigens, although targeting critical mosquito components might also successfully block development of the parasite in its vector. We previously identified A. gambiae genes whose expression was modified in P. falciparum-infected mosquitoes, including one midgut carboxypeptidase gene, cpbAg1. Here we show that P. falciparum up-regulates the expression of cpbAg1 and of a second midgut carboxypeptidase gene, cpbAg2, and that this up-regulation correlates with an increased carboxypeptidase B (CPB) activity at a time when parasites establish infection in the mosquito midgut. The addition of antibodies directed against CPBAg1 to a P. falciparum-containing blood meal inhibited CPB activity and blocked parasite development in the mosquito midgut. Furthermore, the development of the rodent parasite Plasmodium berghei was significantly reduced in mosquitoes fed on infected mice that had been immunized with recombinant CPBAg1. Lastly, mosquitoes fed on anti-CPBAg1 antibodies exhibited reduced reproductive capacity, a secondary effect of a CPB based TBV that could likely contribute to reducing Plasmodium transmission. These results indicate that A. gambiae CPBs could constitute targets for a TBV that is based upon mosquito molecules. PMID- 17283099 TI - Screening of an antigen target for immunocontraceptives from cross-reactive antigens between human sperm and Ureaplasma urealyticum. AB - Epidemiologic studies indicated that some infertile men who were infected with Ureaplasma urealyticum displayed positive antisperm antibodies in their serum and/or semen. The purpose of this study was to investigate the possible mechanism of antisperm antibodies production after infection with U. urealyticum and to analyze the relationship between U. urealyticum and infertility. The existence of cross-reactive antigens (61, 50, and 25 kDa) between U. urealyticum and human sperm membrane proteins was confirmed. Among the cross-reactive antigens, the urease complex component UreG of U. urealyticum was determined. By searching the Swiss-Prot protein database, a pentapeptide identity (IERLT) between UreG and human nuclear autoantigenic sperm protein (NASP) was found. Furthermore, using Western blot analysis and enzyme-linked immunosorbent assay, the cross-reaction between the NASP and UreG was verified. Both anti-rUreG antibody and the antiserum against the synthetic peptide NASP393-408 containing the pentapeptide inhibited mouse sperm egg binding and fusion. After immunization by rUreG or the synthetic peptide, 81.2 and 75% female mice became sterile, respectively. The effect on fertility in mice immunized with the synthetic peptide was reversible. These findings proved for the first time that it was feasible to screen antigens for immunocontraceptives from cross-reactive antigens between sperm and microorganisms which induce infertility. PMID- 17283101 TI - Solitary intestinal lymphoid tissue provides a productive port of entry for Salmonella enterica serovar Typhimurium. AB - Oral infection of mice with Salmonella enterica serovar Typhimurium results in the colonization of Peyer's patches, triggering a vigorous inflammatory response and immunopathology at these sites. Here we demonstrate that in parallel to Peyer's patches a strong inflammatory response occurs in the intestine, resulting in the appearance of numerous inflammatory foci in the intestinal mucosa. These foci surround small lymphoid cell clusters termed solitary intestinal lymphoid tissue (SILT). Salmonella can be observed inside SILT at early stages of infection, and the number of infected structures matches the number of inflammatory foci arising at later time points. Infection leads to enlargement and morphological destruction of SILT but does not trigger de novo formation of lymphoid tissue. In conclusion, SILT, a lymphoid compartment mostly neglected in earlier studies, represents a major site for Salmonella invasion and ensuing mucosal pathology. PMID- 17283102 TI - Regulation of exoprotein gene expression by the Staphylococcus aureus cvfB gene. AB - We previously reported that the cvfB gene (SA1223) of Staphylococcus aureus is responsible for the virulence of this pathogenic bacterium. We show here that the cvfB gene regulates exoprotein gene expression. In a cvfB gene deletion mutant, hemolysin, DNase, and protease production were decreased, whereas protein A expression was increased. The amount of RNAIII, the transcript from the P3 promoter in the agr locus that regulates the expression of various virulence factors, was also reduced in the cvfB mutant. In addition, P2 and P3 promoter activity in the agr locus was decreased in the mutant. Under the genetic background of the agr-null mutation, cvfB gene disruption decreased the production levels of DNase and protease. Moreover, the cvfB and agr double mutant was less virulent than the agr mutant in silkworms. These results suggest that the cvfB gene product contributes to the expression of virulence factors and to pathogenicity via both agr-dependent and agr-independent pathways. PMID- 17283103 TI - Antigen-specific CD4+ T cells recognize epitopes of protective antigen following vaccination with an anthrax vaccine. AB - Detection of antigen-specific CD4+ T cells is facilitated by the use of fluorescently labeled soluble peptide-major histocompatibility complex (MHC) multimers which mirror the antigen specificity of T-cell receptor recognition. We have used soluble peptide-MHC class II tetramers containing peptides from the protective antigen (PA) of Bacillus anthracis to detect circulating T cells in peripheral blood of subjects vaccinated with an anthrax vaccine. PA-specific HLA class II-restricted T lymphocytes were isolated which displayed both TH1- and TH2 like characteristics, indicating heterogeneity of the lymphocyte lineage within the CD4+ response. Presentation of antigen to these T-cell clones by HLA-matched antigen-presenting cells exposed to the intact PA protein confirmed that the identified epitopes are indeed naturally processed by the human immune system. Specific tetramer-derived T-cell profiling may be useful for monitoring helper CD4+ T-cell responses to anthrax vaccination. PMID- 17283104 TI - Guinea pig neutrophils infected with Mycobacterium tuberculosis produce cytokines which activate alveolar macrophages in noncontact cultures. AB - The early influx of neutrophils to the site of infection may be an important step in host resistance against Mycobacterium tuberculosis. In this study, we investigated the effect of M. tuberculosis infection on the ability of guinea pig neutrophils to produce interleukin-8 (IL-8; CXCL8) and tumor necrosis factor alpha (TNF-alpha) and to activate alveolar macrophages. Neutrophils and alveolar macrophages were isolated from naive guinea pigs, cultured together or alone, and infected with virulent M. tuberculosis for 3, 12, and 24 h. IL-8 protein production in cocultures, as measured by using an enzyme-linked immunosorbent assay, was found to be additive at 24 h and significantly greater in M. tuberculosis-infected cocultures than in uninfected cocultures and in cultures of the infected neutrophils or macrophages alone. The IL-8 mRNA levels, determined by real-time reverse transcription-PCR, were elevated at 24 h in infected cocultures and infected cells cultured alone. In order to elucidate the contributions of neutrophils and their soluble mediators to the activation of alveolar macrophages, neutrophils and alveolar macrophages were cultured in a contact-independent manner by using a Transwell insert system. Neutrophils were infected with virulent M. tuberculosis in the upper wells, and alveolar macrophages were cultured in the lower wells. The release of hydrogen peroxide from alveolar macrophages exposed to soluble products from infected neutrophils was significantly increased compared to that from unexposed alveolar macrophages. Significant up-regulation of IL-1beta and TNF-alpha mRNA levels in alveolar macrophages was observed at 24 and 30 h, respectively, compared to those in cells not exposed to soluble neutrophil products. Treatment with anti-guinea pig TNF alpha polyclonal antibody completely abolished the response of alveolar macrophages to neutrophil products. This finding suggests that TNF-alpha produced by infected neutrophils may be involved in the activation of alveolar macrophages and hence may contribute to the containment of M. tuberculosis infection during the early period of infection. PMID- 17283105 TI - Induction of monocyte chemotactic protein 1 in colonic epithelial cells by Entamoeba histolytica is mediated via the phosphatidylinositol 3-kinase/p65 pathway. AB - The role intestinal epithelial cells play in the pathogenesis of amebic colitis is poorly understood. Herein, we demonstrate that secreted and soluble ameba (Entamoeba histolytica) proteins (SAP) induce expression of the chemoattractant monocyte chemotactic protein (MCP) in the colonic epithelial cell lines Caco-2, T84, and LS174T. MCP-1 mRNA induction was both dose and time dependent, with peak induction occurring at 8 h and with 100 mug/ml of SAP. Significant increase in MCP-1 protein expression was observed after 12 h. SAP failed to activate any of the mitogen-activated protein kinase pathways or IkappaB kinase activity. Moreover, inhibiting the classical pathway of NF-kappaB activation did not affect SAP-induced MCP-1 expression. Instead, we find that SAP-induced MCP-1 expression is dependent on posttranslational modification of the NFkappaB p65 subunit. SAP induced phosphorylation of p65 and enhanced NF-kappaB transcriptional activity, which are phosphatidylinositol 3-kinase (PI3 kinase) dependent. Treatment with PI3 kinase inhibitor LY290004 significantly abrogated the activation of Akt, p65, and MCP-1 mRNA induction. We conclude that colonic epithelial cells play a role in the initiation of inflammation by secreting chemokines in response to soluble ameba components. PMID- 17283107 TI - Dependence of macrophage phagocytic efficacy on antibody concentration. AB - Macrophages ingest the fungus Cryptococcus neoformans only in the presence of opsonins, and this provides a remarkably clean system for the detailed analysis of phagocytosis. This system is also unusual in that antibody-mediated phagocytosis involves ingestion through both Fc and complement receptors in the absence of complement. Mathematical modeling was used to analyze and explain the experimental data that the macrophage phagocytic index increased with increasing doses of antibody despite saturating concentrations and declined at high concentrations. A model was developed that explains the increase in phagocytic index with increasing antibody doses, differentiates among the contributions from Fc and complement receptors, and provides a tool for estimating antibody concentrations that optimize efficacy of phagocytosis. Experimental results and model calculations revealed that blocking of Fc receptors by excess antibody caused a reduction in phagocytic index but increased phagocytosis through complement receptors rapidly compensated for this effect. At high antibody concentrations, a further reduction in phagocytic index was caused by interference with complement receptor ingestion as a consequence of saturation of the fungal capsule. The ability of our model to predict the antibody dose dependence of the macrophage phagocytic efficacy for C. neoformans strongly suggest that the major variables that determine the efficacy of this process have been identified. The model predicts that the affinity constant of the opsonic antibody for the Fc receptor and the association-dissociation constant of antibody from the microbial antigen are critical parameters determining the efficacy of phagocytosis. PMID- 17283106 TI - Inflammatory lipoproteins purified from a toxigenic and arthritogenic strain of Mycoplasma arthritidis are dependent on Toll-like receptor 2 and CD14. AB - Mycoplasma arthritidis is a naturally occurring murine pathogen, and the disease model has been used extensively to understand inflammatory mechanisms. Recently, Triton X-114 extracts of a virulent strain of M. arthritidis were found to be more potent in activating macrophages than were those from an avirulent strain, suggesting a role in disease. Here, octyl glucoside extraction of cells was used to identify four distinct bioactive moieties, with molecular masses of approximately 41, 37, 34, and 17 kDa. Their bioactivities were resistant to proteinase K but were destroyed by alkaline hydrolysis and oxidation. As for MALP 2, all were dependent upon Toll-like receptor 2, but unlike MALP-2, they were also dependent upon CD14. The M. arthritidis lipoproteins exhibited infrared absorbances at 2,900 cm(-1) and 1,662 cm(-1), similar to those seen in Pam(3)-Cys Ser-(Lys)(4). Edman degradation failed to reveal N-terminal sequences, suggesting that they were blocked and therefore might be triacylated. However, mass spectrometry of fragments revealed that the 41-kDa moiety, which binds to serum apolipoprotein A-1, had similarity with the recently described MlpD lipoprotein of M. arthritidis. PMID- 17283108 TI - The putative glycosyltransferase-encoding gene cylJ and the group B Streptococcus (GBS)-specific gene cylK modulate hemolysin production and virulence of GBS. AB - Group B streptococcus (GBS) expresses a hemolysin/cytolysin that plays an important role in pathogenesis. Using the Himar1 transposon mutagenesis system, a hypohemolytic mutant carrying an interrupted cylJ gene was characterized. cylJ, encoding a putative glycosyltransferase, and cylK, whose product is unknown, are both required for the full hemolytic/cytolytic activity, pigment formation, and virulence of GBS. PMID- 17283109 TI - The rag locus of Porphyromonas gingivalis contributes to virulence in a murine model of soft tissue destruction. AB - The rag locus of Porphyromonas gingivalis encodes a putative TonB-dependent outer membrane receptor, RagA, and a 55-kDa immunodominant antigen, RagB. Inactivation of either ragA or ragB prevented expression of both RagA and RagB. Both the ragA and ragB mutants were significantly less virulent than wild-type strains in a murine model of infection. PMID- 17283110 TI - Breast cancer: should gastrointestinal bacteria be on our radar screen? AB - Anti-inflammatory drugs and antibiotics alter the risk of breast cancer in women, but roles for bacteria and inflammation in breast malignancies are poorly understood. A recent study in mice suggests that intestinal bacteria can trigger mammary carcinoma. The mechanisms involved in this effect suggest that dysregulated host immune responses to enteric bacteria can influence the development of extraintestinal cancers, highlighting the opportunities for prevention and treatment aimed at promoting intestinal homeostasis. PMID- 17283111 TI - Therapy-induced tumor immunosurveillance involves IFN-producing killer dendritic cells. AB - A unique class of IFN-producing killer dendritic cells (IKDC) resembling natural killer cells has been defined that can recognize and lyse tumor cells through a tumor necrosis factor-related apoptosis-inducing ligand-dependent mechanism. IKDC may mediate the host-dependent antitumor activity of Gleevec/STI571 and other therapeutics that can inhibit the c-kit tyrosine kinase. IKDC represent an important new component of the innate immune system responding to cancer. PMID- 17283112 TI - Intermittent hypoxia furthers the rationale for hypoxia-inducible factor-1 targeting. AB - Hypoxia-inducible factor-1 (HIF-1) stabilization is a pivotal event in the response to hypoxic stress. A study in the December 15, 2006 issue of Cancer Research shows that HIF-1 stabilization occurs more robustly as a result of intermittent hypoxia compared with chronic hypoxia. The findings of this study suggest that intermittent hypoxia might influence the efficacy of radiotherapy by more strongly affecting the growth and survival of vascular endothelial cells. This finding offers additional encouragement to efforts to target HIF-1 for cancer therapy. PMID- 17283113 TI - A look inside the National Cancer Institute budget process: implications for 2007 and beyond. PMID- 17283114 TI - Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. AB - Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear hormone receptor superfamily, which plays an essential role in regulating bile acid, lipid, and glucose homeostasis. Both male and female FXR(-/-) mice spontaneously developed liver tumors; however, no other tumors were developed after 15 months of age. In contrast, no liver tumors were observed in wild-type mice of the same age. Histologic analyses confirm that tumors were hepatocellular adenoma and carcinoma. Although there was no obvious tumor at ages 9 to 12 months, FXR(-/-) livers displayed prominent liver injury and inflammation. Strong labeling of apoptotic hepatocytes and liver damage-induced compensatory regeneration were observed. Deregulation of genes involved in bile acid homeostasis in FXR(-/-) mice was consistent with abnormal levels of bile acids presented in serum and liver. Genes involved in inflammation and cell cycle were up-regulated in aging FXR(-/-) mice but not in wild-type controls. Increasing the bile acid levels by feeding mice with a 0.2% cholic acid diet strongly promoted N-nitrosodiethylamine initiated liver tumorigenesis, whereas lowering bile acid pool in FXR(-/-) mice by a 2% cholestyramine feeding significantly reduced the malignant lesions. Our results suggest an intriguing link between metabolic regulation and hepatocarcinogenesis. PMID- 17283115 TI - Risks for familial and contralateral breast cancer interact multiplicatively and cause a high risk. AB - The reasons for the high risk of contralateral breast cancer are not understood, although polygenic mechanisms have been suggested to be involved. The nationwide Swedish Family-Cancer Database was used to examine the interaction of the risks for contralateral and familial cancer. Relative risks were separately determined for contralateral and familial breast cancers, and these were tested for additive and multiplicative interactions. The Database contained information on 102,176 first breast cancers. Familial risk for breast cancer was 1.76 and the risk for contralateral breast cancer was 3.40, or 5.80 when extrapolated to two breasts. When women had a family history, the risk for contralateral breast cancer was remarkably high, 5.48, or 9.96 when the risk was extrapolated to two breasts, almost identical with 10.21, which was predicted by the multiplicative model. Although the data do not rule out polygenic mechanisms, they suggest that epigenetic imprinting events may be involved for the contralateral breast cancer. PMID- 17283116 TI - Establishment of a new interleukin-6 (IL-6) receptor inhibitor applicable to the gene therapy for IL-6-dependent tumor. AB - Interleukin-6 (IL-6) is a key molecule involved in the pathogenesis of several inflammatory diseases and malignancies. Treatments that inhibit IL-6 mitigate the clinical conditions of such diseases. Here, we report on the development of a new receptor inhibitor of IL-6 (NRI) by genetically engineering tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody which specifically blocks IL-6 signaling. This NRI consists of VH and VL of tocilizumab in a single-chain fragment format dimerized by fusing to the Fc portion of human immunoglobulin G(1). The binding activity to IL-6 receptor and the biological activity of the purified NRI were found to be similar to those of parental tocilizumab. Because NRI is encoded on a single gene, it is easily applicable to a gene delivery system using virus vehicles. We administered an adenovirus vector encoding NRI to mouse i.p. and monitored the serum NRI level and growth reduction property on S6B45, an IL-6-dependent multiple myeloma cell line, in vivo. Adequate amount of the serum NRI level to exert anti-IL-6 action could be obtained by the NRI gene introduction combined with adenovirus gene delivery, and this treatment inhibited the in vivo S6B45 cell growth significantly. These findings indicate that NRI is a promising agent applicable to the therapeutic gene delivery approach for IL-6 driven diseases. PMID- 17283117 TI - Changes in DNA methylation patterns in subjects exposed to low-dose benzene. AB - Aberrant DNA methylation patterns, including global hypomethylation, gene specific hypermethylation/hypomethylation, and loss of imprinting (LOI), are common in acute myelogenous leukemia (AML) and other cancer tissues. We investigated for the first time whether such epigenetic changes are induced in healthy subjects by low-level exposure to benzene, a widespread pollutant associated with AML risk. Blood DNA samples and exposure data were obtained from subjects with different levels of benzene exposure, including 78 gas station attendants, 77 traffic police officers, and 58 unexposed referents in Milan, Italy (personal airborne benzene range, < 6-478 microg/m(3)). Bisulfite-PCR pyrosequencing was used to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and AluI repetitive elements as a surrogate of genome wide methylation and examine gene-specific methylation of MAGE-1 and p15. Allele specific pyrosequencing of the H19 gene was used to detect LOI in 96 subjects heterozygous for the H19 imprinting center G/A single-nucleotide polymorphism. Airborne benzene was associated with a significant reduction in LINE-1 (-2.33% for a 10-fold increase in airborne benzene levels; P = 0.009) and AluI (-1.00%; P = 0.027) methylation. Hypermethylation in p15 (+0.35%; P = 0.018) and hypomethylation in MAGE-1 (-0.49%; P = 0.049) were associated with increasing airborne benzene levels. LOI was found only in exposed subjects (4 of 73, 5.5%) and not in referents (0 of 23, 0.0%). However, LOI was not significantly associated with airborne benzene (P > 0.20). This is the first human study to link altered DNA methylation, reproducing the aberrant epigenetic patterns found in malignant cells, to low-level carcinogen exposure. PMID- 17283118 TI - Hematopoietic prostaglandin D synthase suppresses intestinal adenomas in ApcMin/+ mice. AB - Aspirin and other nonsteroidal anti-inflammatory drugs prevent some cases of colon cancer by inhibiting prostaglandin (PG) synthesis. PGE(2) promotes colon neoplasia, as shown by knockout mouse studies on enzymes and receptors in the PG cascade. A few experiments 20 to 30 years ago suggested that PGD(2) may suppress tumors, but a role for biosynthetic enzymes for PGD(2) in tumor development has not been studied. We report here that disruption of the gene for hematopoietic PGD synthase in Apc(Min/+) mice led to approximately 50% more intestinal adenomas compared with controls. Tumor size was not affected. By immunohistochemistry, we detected hematopoietic PGD synthase mainly in macrophages and monocytes of the gut mucosa. The mean number of tumors did not increase with knockout of the gene for the lipocalin type of the enzyme, which is not produced in the intestine. On the other hand, Apc(Min/+) mice with transgenic human hematopoietic PGD synthase tended to have 80% fewer intestinal adenomas. The transgene produced high mRNA levels (375-fold over endogenous). There was a suggestion of higher urinary excretion of 11beta-PGF(2alpha) and a lower excretion of a PGE(2) metabolite in transgenic mice, but differences (30-40%) were not statistically significant. The results support an interpretation that hematopoietic PGD synthase controls an inhibitory effect on intestinal tumors. Further studies will be needed to prove possible mechanisms, such as routing of PG production away from protumorigenic PGE(2) or inhibition of the nuclear factor-kappaB cascade by PGD(2) metabolites. PMID- 17283119 TI - Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. AB - Pilocytic astrocytomas (PAs) are the most common glioma in children. Whereas many PAs are slow-growing or clinically indolent, others exhibit more aggressive features with tumor recurrence and death. To identify genetic signatures that might predict PA clinical behavior, we did gene expression profiling on 41 primary PAs arising sporadically and in patients with neurofibromatosis type 1 (NF1). Whereas no expression signature was found that could discriminate clinically aggressive or recurrent tumors from more indolent cases, PAs arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we identified a gene expression signature that stratified PAs by location (supratentorial versus infratentorial). Lastly, we also identified a gene expression pattern common to PAs and normal mouse astrocytes and neural stem cells from these distinct brain regions as well as a gene expression pattern shared between PAs and another human glial tumor (ependymoma) arising supratentorially compared with those originating in the posterior fossa. These results suggest that glial tumors share an intrinsic, lineage-specific molecular signature that reflects the brain region in which their nonmalignant predecessors originated. PMID- 17283120 TI - Tbx3 is a downstream target of the Wnt/beta-catenin pathway and a critical mediator of beta-catenin survival functions in liver cancer. AB - Tbx3 encodes a transcriptional repressor that is important for diverse patterning events during development, and Tbx3 mutation in humans causes the ulnar-mammary syndrome. Here, we describe the identification of Tbx3 in array-based search for genes downstream Wnt/beta-catenin that are implicated in liver tumorigenesis. Overexpression of Tbx3 is closely associated with the mutational status of beta catenin in murine liver tumors induced by Myc as well as in human hepatocellular carcinomas and hepatoblastomas. Moreover, Tbx3 transcription is activated by ectopic expression of beta-catenin in mouse liver and in human tumor cell lines. Evidence that Tbx3 transcription is directly regulated by beta-catenin is provided by chromatin immunoprecipitation and reporter assays. Although HepG2 cells stably transfected with Tbx3 display moderately enhanced growth rate, the dominant negative mutant Tbx3-Y149S drastically inhibits hepatoma cell growth in vitro and in vivo. Moreover, small interfering RNAs (siRNA) directed against Tbx3 inhibit anchorage-independent growth of liver and colon carcinoma cells. We further show that inhibition of Tbx3 expression by specific siRNAs blocks beta catenin-mediated cell survival and renders cells sensitive to doxorubicin-induced apoptosis. Conversely, ectopic expression of Tbx3 inhibits apoptosis induced by beta-catenin depletion. Marked overexpression of Tbx3 in a subset of hepatoblastomas is associated with chemotherapy-resistant phenotype and unfavorable patient outcome. These results reveal an unsuspected role of Tbx3 as a mediator of beta-catenin activities on cell proliferation and survival and as an important player in liver tumorigenesis. PMID- 17283121 TI - Ku70 and poly(ADP-ribose) polymerase-1 competitively regulate beta-catenin and T cell factor-4-mediated gene transactivation: possible linkage of DNA damage recognition and Wnt signaling. AB - Formation of the T-cell factor-4 (TCF-4) and beta-catenin nuclear complex is considered crucial to embryonic development and colorectal carcinogenesis. We previously reported that poly(ADP-ribose) polymerase-1 (PARP-1) interacts with the TCF-4 and beta-catenin complex and enhances its transcriptional activity. However, its biological significance remains unexplained. Using immunoprecipitation and mass spectrometry, we found that two Ku proteins, Ku70 and Ku80, were also associated with the complex. Knockdown of Ku70 by RNA interference increased the amount of beta-catenin associated with TCF-4 and enhanced the transcriptional activity. PARP-1 competed with Ku70 for binding to TCF-4. Treatment with bleomycin, a DNA-damaging alkylating agent, induced polyADP ribosylation of PARP-1 protein and inhibited its interaction with TCF-4. Bleomycin conversely increased the amounts of Ku70 coimmunoprecipitated with TCF 4 and removed beta-catenin from TCF-4. We propose a working model in which the transcriptional activity of TCF-4 is regulated by the relative amount of Ku70, PARP-1, and beta-catenin proteins binding to TCF-4. Identification of the functional interaction of Ku70 as well as PARP-1 with the TCF-4 and beta-catenin transcriptional complex may provide insights into a novel linkage between DNA damage recognition/repair and Wnt signaling. PMID- 17283122 TI - TFE3 fusions activate MET signaling by transcriptional up-regulation, defining another class of tumors as candidates for therapeutic MET inhibition. AB - Specific chromosomal translocations encoding chimeric transcription factors are considered to play crucial oncogenic roles in a variety of human cancers but the fusion proteins themselves seldom represent suitable therapeutic targets. Oncogenic TFE3 fusion proteins define a subset of pediatric renal adenocarcinomas and one fusion (ASPL-TFE3) is also characteristic of alveolar soft part sarcoma (ASPS). By expression profiling, we identified the MET receptor tyrosine kinase gene as significantly overexpressed in ASPS relative to four other types of primitive sarcomas. We therefore examined MET as a direct transcriptional target of ASPL-TFE3. ASPL-TFE3 binds to the MET promoter and strongly activates it. Likewise, PSF-TFE3 and NONO-TFE3 also bind this promoter. Induction of MET by ASPL-TFE3 results in strong MET autophosphorylation and activation of downstream signaling in the presence of hepatocyte growth factor (HGF). In cancer cell lines containing endogenous TFE3 fusion proteins, inhibiting MET by RNA interference or by the inhibitor PHA665752 abolishes HGF-dependent MET activation, causing decreased cell growth and loss of HGF-dependent phenotypes. MET is thus a potential therapeutic target in these cancers. Aberrant transcriptional up regulation of MET by oncogenic TFE3 fusion proteins represents another mechanism by which certain cancers become dependent on MET signaling. The identification of kinase signaling pathways transcriptionally up-regulated by oncogenic fusion proteins may reveal more accessible therapeutic targets in this class of human cancers. PMID- 17283123 TI - Demethylation-linked activation of urokinase plasminogen activator is involved in progression of prostate cancer. AB - Increased expression of urokinase plasminogen activator (uPA) has been reported in various malignancies including prostate cancer. However, the mechanism by which uPA is abnormally expressed in prostate cancer remains elusive. Here, we show that uPA is aberrantly expressed in a high percentage of human prostate cancer tissues but rarely expressed either in tumor-matched nonneoplastic adjacent tissues or benign prostatic hyperplasia samples. This aberrant expression is associated with cancer-linked demethylation of the uPA promoter. Furthermore, treatment with demethylation inhibitor S-adenosylmethionine or stable expression of uPA short hairpin RNA significantly inhibits uPA expression and tumor cell invasion in vitro and tumor growth and incidence of lung metastasis in vivo. Collectively, these findings strongly suggest that DNA demethylation is a common mechanism underlying the abnormal expression of uPA and is a critical contributing factor to the malignant progression of human prostate tumors. PMID- 17283124 TI - 5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity. AB - 5-Fluorouracil (FU) has been widely used for more than four decades in the treatment of a range of common cancers. The fluorine-substituted uracil analogue is converted to several active metabolites but the mechanism of cytotoxicity has remained unclear. In a widely cited but unsubstantiated model, FU is thought to kill cells via the inhibition of thymidylate synthase and increased use of dUTP in place of TTP during DNA replication, with subsequent excision of high levels of uracil causing the fragmentation of newly synthesized DNA. Using gene-targeted cell lines defective in one or both of the two mammalian uracil-DNA glycosylase repair enzymes, we were able to test this model of FU cytotoxicity. Here, we show that incorporation of FU itself into DNA has been previously underestimated and is a predominant cause of cytotoxicity. FU readily becomes incorporated into the DNA of drug-treated cells, and accumulation of FU in the genome, rather than uracil excision, is correlated with FU cytotoxicity in mammalian cells. Furthermore, the Smug1, but not the Ung, uracil-DNA glycosylase excises FU from DNA and protects against cell killing. The data provides a clearer understanding of the action of FU, suggesting predictive biomarkers of drug response and a mechanism for acquired resistance in tumors. PMID- 17283125 TI - Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. AB - Alterations in cytosine methylation patterns are usually observed in human tumors. The consequences of altered cytosine methylation patterns include both inappropriate activation of transforming genes and silencing of tumor suppressor genes. Despite the biological effect of methylation changes, little is known about how such changes are caused. The heritability of cytosine methylation patterns from parent to progeny cells is attributed to the fidelity of the methylation-sensitive human maintenance methyltransferase DNMT1, which methylates with high specificity the unmethylated strand of a hemimethylated CpG sequence following DNA replication. We have been studying DNA damage that might alter the specificity of DNMT1, either inhibiting the methylation of hemimethylated sites or triggering the inappropriate methylation of previously unmethylated sites. Here, we show that known forms of endogenous DNA damage can cause either hypermethylation or hypomethylation. Inflammation-induced 5-halogenated cytosine damage products, including 5-chlorocytosine, mimic 5-methylcytosine and induce inappropriate DNMT1 methylation within a CpG sequence. In contrast, oxidation damage of the methyl group of 5-methylcytosine, with the formation of 5 hydroxymethylcytosine, prevents DNMT1 methylation of the target cytosine. We propose that reduced DNMT1 selectivity resulting from DNA damage could cause heritable changes in cytosine methylation patterns, resulting in human tumor formation. These data may provide a mechanistic link for the associations documented between inflammation and cancer. PMID- 17283126 TI - BRCA1 ubiquitinates RPB8 in response to DNA damage. AB - The breast and ovarian tumor suppressor BRCA1 catalyzes untraditional polyubiquitin chains that could be a signal for processes other than proteolysis. However, despite intense investigations, the mechanisms regulated by the enzyme activity remain only partially understood. Here, we report that BRCA1-BARD1 mediates polyubiquitination of RPB8, a common subunit of RNA polymerases, in response to DNA damage. A proteomics screen identified RPB8 as a protein modified after epirubicin treatment in BRCA1-dependent manner. RPB8 interacted with BRCA1 BARD1 and was polyubiquitinated by BRCA1-BARD1 in vivo and in vitro. BRCA1-BARD1 did not destabilize RPB8 in vivo but rather caused an increase in the amount of soluble RPB8. Importantly, RPB8 was polyubiquitinated immediately after UV irradiation in a manner sensitive to BRCA1 knockdown by RNA interference. Substitution of five lysine residues of RPB8 with arginine residues abolished its ability to be ubiquitinated while preserving its polymerase activity. HeLa cell lines stably expressing this ubiquitin-resistant form of RPB8 exhibited UV hypersensitivity accompanied by up-regulated caspase activity. Our findings suggest that ubiquitination of a common subunit of RNA polymerases is a mechanism underlying BRCA1-dependent cell survival after DNA damage. PMID- 17283127 TI - Pten loss in the mouse thyroid causes goiter and follicular adenomas: insights into thyroid function and Cowden disease pathogenesis. AB - Inactivation and silencing of the tumor suppressor PTEN are found in many different epithelial tumors, including thyroid neoplasia. Cowden Disease patients, who harbor germ-line PTEN mutations, often display thyroid abnormalities, including multinodular goiter and follicular adenomas, and are at increased risk of thyroid cancer. To gain insights into the role PTEN plays in thyroid function and disease, we have generated a mouse strain, in which Cre mediated recombination is used to specifically delete Pten in the thyrocytes. We found that Pten mutant mice develop diffuse goiter characterized by extremely enlarged follicles, in the presence of normal thyroid-stimulating hormone and T4 hormone levels. Loss of Pten resulted in a significant increase in the thyrocyte proliferative index, which was more prominent in the female mice, and in increased cell density in the female thyroid glands. Surprisingly, goitrogen treatment did not cause a substantial increase of the mutant thyroid size and increased only to some extent the proliferation index of the female thyrocytes, suggesting that a relevant part of the thyroid-stimulating hormone-induced proliferation signals are funneled through the phosphatidylinositol-3-kinase (PI3K)/Akt cascade. Although complete loss of Pten was not sufficient to cause invasive tumors, over two thirds of the mutant females developed follicular adenomas by 10 months of age, showing that loss of Pten renders the thyroid highly susceptible to neoplastic transformation through mechanisms that include increased thyrocyte proliferation. Our findings show that constitutive activation of the PI3K/Akt cascade is sufficient to stimulate continuous autonomous growth and provide novel clues to the pathogenesis of Cowden Disease and sporadic nontoxic goiter. PMID- 17283128 TI - The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. AB - The precise molecular mechanisms by which prostate cancer cells progress from androgen-sensitive to androgen-insensitive status still remain largely unclear. The hepatocyte growth factor/scatter factor (HGF/SF) plays a critical role in the regulation of cell growth, cell motility, morphogenesis, and angiogenesis. The aberrant expression of HGF/SF and its receptor, c-Met, often correlates with poor prognosis in a variety of human malignancies, including prostate cancer. Here, we investigate a potential link between androgen signaling and c-Met expression in prostate cancer cells. First, we showed that the androgen receptor (AR) represses the expression of c-Met in a ligand-dependent manner. Using different c-Met promoter/reporter constructs, we identified that Sp1 induces the transcription of c-Met and that AR can repress the Sp1-induced transcription in prostate cancer cells. Moreover, the data from electrophoretic mobility shift assay showed that AR interferes with the interaction between Sp1 and the functional Sp1 binding site within the c-Met promoter. Furthermore, we tested the effect of AR on c-Met expression in an androgen-insensitive prostate cancer cell line, CWR22Rv1. Finally, the repressive role of androgen signaling on c-Met expression was confirmed in prostate cancer xenografts. The above data indicate a dual role of AR in transcriptional regulation. Although the current androgen ablation therapy can repress the expression of growth-promoting genes that are activated by the AR, it may also attenuate the repressive role of AR on c-Met expression. Therefore, the therapeutic strategies to inhibit the activation of the HGF/c-Met pathway may be of benefit when combined with current androgen ablation treatment. PMID- 17283129 TI - Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. AB - Neuroblastoma accounts for 15% of pediatric cancer deaths, and although a few protein-coding genes, such as MYCN, are involved with aggressive pathogenicity, the identification of novel biological targets for therapeutic intervention is still a necessary prerequisite for improving patient survival. Expression profiling of 157 microRNA (miRNA) loci in 35 primary neuroblastoma tumors indicates that 32 loci are differentially expressed in favorable and unfavorable tumor subtypes, indicating a potential role of miRNAs in neuroblastoma pathogenesis. Many of these loci are significantly underexpressed in tumors with MYCN amplification, which have particularly poor prognoses. Interestingly, we found that miRNA expression levels substantially change in a MYCN-amplified cell line following exposure to retinoic acid, a compound which is well known for causing reductions in MYCN expression and for inducing neuroblastoma cell lines to undergo neuronal differentiation. We also show that small interfering RNA inhibition of MYCN by itself causes similar alterations in the expression of miRNA loci. In vitro functional studies of one locus, miR-184, indicate that it plays a significant role in apoptosis. The association of experimentally induced alterations of miRNA expression in neuroblastoma cell lines with differentiation or apoptosis leads us to conclude that these loci play important roles in neuroblastoma pathogenesis. We further suggest that MYCN may mediate a tumorigenic effect, in part, through directly or indirectly regulating the expression of miRNAs that are involved with neural cell differentiation and/or apoptosis, warranting substantial further studies of miRNAs as potential therapeutic targets. PMID- 17283130 TI - Deregulated CDC25A expression promotes mammary tumorigenesis with genomic instability. AB - Checkpoint pathways help cells maintain genomic integrity, delaying cell cycle progression in response to various risks of fidelity, such as genotoxic stresses, compromised DNA replication, and impaired spindle control. Cancer cells frequently exhibit genomic instability, and recent studies showed that checkpoint pathways are likely to serve as a tumor-suppressive barrier in vivo. The cell cycle-promoting phosphatase CDC25A is an activator of cyclin-dependent kinases and one of the downstream targets for the CHK1-mediated checkpoint pathway. Whereas CDC25A overexpression is observed in various human cancer tissues, it has not been determined whether deregulated CDC25A expression triggers or promotes tumorigenesis in vivo. Here, we show that transgenic expression of CDC25A cooperates markedly with oncogenic ras or neu in murine mammary tumorigenesis. MMTV-CDC25A transgenic mice exhibit alveolar hyperplasia in the mammary tissue but do not develop spontaneous mammary tumors. The MMTV-CDC25A transgene markedly shortens latency of tumorigenesis in MMTV-ras mice. The MMTV-CDC25A transgene also accelerates tumor growth in MMTV-neu mice with apparent cell cycle miscoordination. CDC25A-overexpressing tumors, which invade more aggressively, exhibit various chromosomal aberrations on fragile regions, including the mouse counterpart of human 1p31-36, according to array-based comparative genomic hybridization and karyotyping. The chromosomal aberrations account for substantial changes in gene expression profile rendered by transgenic expression of CDC25A, including down-regulation of Trp73. These data indicate that deregulated control of cellular CDC25A levels leads to in vivo genomic instability, which cooperates with the neu-ras oncogenic pathway in mammary tumorigenesis. PMID- 17283131 TI - Methylation-independent silencing of the tumor suppressor INK4b (p15) by CBFbeta SMMHC in acute myelogenous leukemia with inv(16). AB - The tumor suppressor gene INK4b (p15) is silenced by CpG island hypermethylation in most acute myelogenous leukemias (AML), and this epigenetic phenomenon can be reversed by treatment with hypomethylating agents. Thus far, it was not investigated whether INK4b is hypermethylated in all cytogenetic subtypes of AML. A comparison of levels of INK4b methylation in AML with the three most common cytogenetic alterations, inv(16), t(8;21), and t(15;17), revealed a strikingly low level of methylation in all leukemias with inv(16) compared with the other types. Surprisingly, the expression level of INK4b in inv(16)+ AML samples was low and comparable with that of the other subtypes. An investigation into an alternative mechanism of INK4b silencing determined that the loss of INK4b expression was caused by inv(16)-encoded core binding factor beta-smooth muscle myosin heavy chain (CBFbeta-SMMHC). The silencing was manifested in an inability to activate the normal expression of INK4b RNA as shown in vitamin D3-treated U937 cells expressing CBFbeta-SMMHC. CBFbeta-SMMHC was shown to displace RUNX1 from a newly determined CBF site in the promoter of INK4b. Importantly, this study (a) establishes that the gene encoding the tumor suppressor p15(INK4b) is a target of CBFbeta-SMMHC, a finding relevant to the leukemogenesis process, and (b) indicates that, in patients with inv(16)-containing AML, reexpression from the INK4b locus in the leukemia would not be predicted to occur using hypomethylating drugs. PMID- 17283132 TI - Molecular and cytogenetical alterations induced by environmental cigarette smoke in mice heterozygous for Fhit. AB - Previous studies in humans and animal models provided evidence that the Fhit gene is an early target for cigarette smoke. We compared the induction of a variety of molecular and cytogenetical alterations in B6-129(F(1)) mice, either wild type or Fhit(+/-), after whole-body exposure to environmental cigarette smoke (ECS) for 15 consecutive days. Both mouse genotypes responded to ECS with a loss of Fhit protein in the bronchial epithelium, accompanied by induction of apoptosis and stimulation of cell proliferation. ECS induced formation of bulky DNA adducts in whole lung. In addition, ECS caused cytogenetical damage both in the respiratory tract and at a systemic level, as shown by a significant increase of micronucleus frequency in pulmonary alveolar macrophages, bone marrow polychromatic erythrocytes, and peripheral blood normochromatic erythrocytes of both wild-type and Fhit(+/-) mice. These results are compared with those generated in other species, strains, and genotypes of rodents exposed to ECS that we investigated previously. Although the loss of Fhit protein in the bronchial epithelium of ECS exposed B6-129(F(1)) mice provides further evidence that the Fhit gene is an early molecular target for ECS, heterozygosity for Fhit does not seem to confer an increased susceptibility of mice in terms of the investigated early biomarkers. PMID- 17283133 TI - Transforming growth factor-beta, estrogen, and progesterone converge on the regulation of p27Kip1 in the normal and malignant endometrium. AB - Hormones and growth factors regulate endometrial cell growth. Disrupted transforming growth factor-beta (TGF-beta) signaling in primary endometrial carcinoma (ECA) cells leads to loss of TGF-beta-mediated growth inhibition, which we show herein results in lack of up-regulation of the cyclin-dependent kinase inhibitor p27(Kip1) (p27) to arrest cells in G(1) phase of the cell cycle. Conversely, in normal primary endometrial epithelial cells (EECs), TGF-beta induces a dose-dependent increase in p27 protein, with a total 3.6-fold maximal increase at 100 pmol/L TGF-beta, which was 2-fold higher in the nuclear fraction; mRNA levels were unaffected. In addition, ECA tissue lysates show a high rate of ubiquitin-mediated degradation of p27 compared with normal secretory-phase endometrial tissue (SE) such that 4% and 89% of recombinant p27 added to the lysates remains after 3 and 20 h, respectively. These results are reflected in vivo as ECA tissue lacks p27 compared with high expression of p27 in SE (P < or = 0.001). Furthermore, we show that estrogen treatment of EECs causes mitogen activated protein kinase-driven proteasomal degradation of p27 whereas progesterone induces a marked increase in p27 in both normal EECs and ECA cells. Therefore, these data suggest that TGF-beta induces accumulation of p27 for normal growth regulation of EECs. However, in ECA, in addition to enhanced proteasomal degradation of p27, TGF-beta cannot induce p27 levels due to dysregulated TGF-beta signaling, thereby causing 17beta-estradiol-driven p27 degradation to proceed unchecked for cell cycle progression. Thus, p27 may be a central target for growth regulation of normal endometrium and in the pathogenesis of ECA. PMID- 17283135 TI - Identification of pancreatic cancer stem cells. AB - Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Although data have been provided to support this theory in human blood, brain, and breast cancers, the identity of pancreatic cancer stem cells has not been determined. Using a xenograft model in which primary human pancreatic adenocarcinomas were grown in immunocompromised mice, we identified a highly tumorigenic subpopulation of pancreatic cancer cells expressing the cell surface markers CD44, CD24, and epithelial-specific antigen (ESA). Pancreatic cancer cells with the CD44(+)CD24(+)ESA(+) phenotype (0.2-0.8% of pancreatic cancer cells) had a 100-fold increased tumorigenic potential compared with nontumorigenic cancer cells, with 50% of animals injected with as few as 100 CD44(+)CD24(+)ESA(+) cells forming tumors that were histologically indistinguishable from the human tumors from which they originated. The enhanced ability of CD44(+)CD24(+)ESA(+) pancreatic cancer cells to form tumors was confirmed in an orthotopic pancreatic tail injection model. The CD44(+)CD24(+)ESA(+) pancreatic cancer cells showed the stem cell properties of self-renewal, the ability to produce differentiated progeny, and increased expression of the developmental signaling molecule sonic hedgehog. Identification of pancreatic cancer stem cells and further elucidation of the signaling pathways that regulate their growth and survival may provide novel therapeutic approaches to treat pancreatic cancer, which is notoriously resistant to standard chemotherapy and radiation. PMID- 17283134 TI - Knockdown of XAB2 enhances all-trans retinoic acid-induced cellular differentiation in all-trans retinoic acid-sensitive and -resistant cancer cells. AB - Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is composed of 855 amino acids, contains 15 tetratricopeptide repeat motifs, and associates with Cockayne syndrome group A and B proteins and RNA polymerase II, as well as XPA. In vitro and in vivo studies showed that XAB2 is involved in pre-mRNA splicing, transcription, and transcription-coupled DNA repair, leading to preimplantation lethality, and is essential for mouse embryogenesis. Retinoids are effective for the treatment of preneoplastic diseases including xeroderma pigmentosum and other dermatologic diseases such as photoaging. We therefore focused on defining the effect of XAB2 on cellular differentiation in the presence of ATRA treatment. In the present study, we showed that overexpression of XAB2 inhibited ATRA-induced cellular differentiation in human rhabdomyosarcoma cell line, and that knockdown of XAB2 by small interfering RNA (siRNA) increased ATRA-sensitive cellular differentiation in the human promyelocytic leukemia cell line HL60 at both physiologic (10(-9)-10(-8) mol/L) and therapeutic (10(-7) mol/L) concentrations of ATRA. Moreover, we found that XAB2 was associated with retinoic acid receptor alpha (RARalpha) and histone deacetylase 3 in the nuclei. Finally, using siRNA against XAB2, we showed that the ATRA-resistant neuroblastoma cell line IMR-32 underwent cellular differentiation induced by ATRA at a therapeutic concentration (10(-6) mol/L). These results strongly suggest that XAB2 is a component of the RAR corepressor complex with an inhibitory effect on ATRA-induced cellular differentiation and that XAB2 plays a role in ATRA-mediated cellular differentiation as an important aspect of cancer therapy. PMID- 17283136 TI - Colon cancer cell-derived tumor necrosis factor-alpha mediates the tumor growth promoting response in macrophages by up-regulating the colony-stimulating factor 1 pathway. AB - The interplay between malignant and stromal cells is essential in tumorigenesis. We have previously shown that colony-stimulating factor (CSF)-1, matrix metalloprotease (MMP)-2, and vascular endothelial growth factor (VEGF)-A production by stromal cells is enhanced by CSF-1-negative SW620 colon cancer cells. In the present study, the mechanisms by which colon cancer cells up regulate host factors to promote tumorigenesis were investigated. Profiling of tumor cell cytokine expression in SW620 tumor xenografts in nude mice showed increased human tumor necrosis factor (TNF)-alpha mRNA expression with tumor growth. Incubation of macrophages with small interfering (si) RNAs directed against TNF-alpha or TNF-alpha-depleted SW620 cell conditioned medium versus SW620 cell conditioned medium failed to support mouse macrophage proliferation, migration, and expression of CSF-1, VEGF-A, and MMP-2 mRNAs. Consistent with these results, human TNF-alpha gene silencing decreased mouse macrophage TNF alpha, CSF-1, MMP-2, and VEGF-A mRNA expression in macrophages cocultured with human cancer cells. In addition, inhibition of human TNF-alpha or mouse CSF-1 expression by siRNA reduced tumor growth in SW620 tumor xenografts in mice. These results suggest that colon cancer cell-derived TNF-alpha stimulates TNF-alpha and CSF-1 production by macrophages, and that CSF-1, in turn, induces macrophage VEGF A and MMP-2 in an autocrine manner. Thus, interrupting tumor cell-macrophage communication by targeting TNF-alpha may provide an alternative therapeutic approach for the treatment of colon cancer. PMID- 17283138 TI - RASSF1C, an isoform of the tumor suppressor RASSF1A, promotes the accumulation of beta-catenin by interacting with betaTrCP. AB - The Ras-association domain family 1 (RASSF1) gene has seven different isoforms; isoform A is a tumor-suppressor gene (RASSF1A). The promoter of RASSF1A is inactivated in many cancers, whereas the expression of another major isoform, RASSF1C, is not affected. Here, we show that RASSF1C, but not RASSF1A, interacts with betaTrCP. Binding of RASSF1C to betaTrCP involves serine 18 and serine 19 of the SS(18)GYXS(19) motif present in RASSF1C but not in RASSF1A. This motif is reminiscent of the canonical phosphorylation motif recognized by betaTrCP; however, surprisingly, the association between RASSF1C and betaTrCP does not occur via the betaTrCP substrate binding domain, the WD40 repeats. Overexpression of RASSF1C, but not of RASSF1A, resulted in accumulation and transcriptional activation of the beta-catenin oncogene, due to inhibition of its betaTrCP mediated degradation. Silencing of RASSF1A by small interfering RNA was sufficient for beta-catenin to accumulate, whereas silencing of both RASSF1A and RASSF1C had no effect. Thus, RASSF1A and RASSF1C have opposite effects on beta catenin degradation. Our results suggest that RASSF1C expression in the absence of RASSF1A could play a role in tumorigenesis. PMID- 17283137 TI - Extracellular signal-related kinase positively regulates ataxia telangiectasia mutated, homologous recombination repair, and the DNA damage response. AB - The accurate joining of DNA double-strand breaks by homologous recombination repair (HRR) is critical to the long-term survival of the cell. The three major mitogen-activated protein (MAP) kinase (MAPK) signaling pathways, extracellular signal-regulated kinase (ERK), p38, and c-Jun-NH(2)-kinase (JNK), regulate cell growth, survival, and apoptosis. To determine the role of MAPK signaling in HRR, we used a human in vivo I-SceI-based repair system. First, we verified that this repair platform is amenable to pharmacologic manipulation and show that the ataxia telangiectasia mutated (ATM) kinase is critical for HRR. The ATM-specific inhibitor KU-55933 compromised HRR up to 90% in growth-arrested cells, whereas this effect was less pronounced in cycling cells. Then, using well-characterized MAPK small-molecule inhibitors, we show that ERK1/2 and JNK signaling are important positive regulators of HRR in growth-arrested cells. On the other hand, inhibition of the p38 MAPK pathway generated an almost 2-fold stimulation of HRR. When ERK1/2 signaling was stimulated by oncogenic RAF-1, an approximately 2-fold increase in HRR was observed. KU-55933 partly blocked radiation-induced ERK1/2 phosphorylation, suggesting that ATM regulates ERK1/2 signaling. Furthermore, inhibition of MAP/ERK kinase (MEK)/ERK signaling resulted in severely reduced levels of phosphorylated (S1981) ATM foci but not gamma-H2AX foci, and suppressed ATM phosphorylation levels >85% throughout the cell cycle. Collectively, these results show that MAPK signaling positively and negatively regulates HRR in human cells. More specifically, ATM-dependent signaling through the RAF/MEK/ERK pathway is critical for efficient HRR and for radiation-induced ATM activation, suggestive of a regulatory feedback loop between ERK and ATM. PMID- 17283140 TI - Human T-cell leukemia virus oncoprotein tax represses nuclear receptor-dependent transcription by targeting coactivator TAX1BP1. AB - Human T-cell leukemia virus type 1 oncoprotein Tax is a transcriptional regulator that interacts with a large number of host cell factors. Here, we report the novel characterization of the interaction of Tax with a human cell protein named Tax1-binding protein 1 (TAX1BP1). We show that TAX1BP1 is a nuclear receptor coactivator that forms a complex with the glucocorticoid receptor. TAX1BP1 and Tax colocalize into intranuclear speckles that partially overlap with but are not identical to the PML oncogenic domains. Tax binds TAX1BP1 directly, induces the dissociation of TAX1BP1 from the glucocorticoid receptor-containing protein complex, and represses the coactivator function of TAX1BP1. Genetic knockout of Tax1bp1 in mice abrogates the influence of Tax on the activation of nuclear receptors. We propose that Tax-TAX1BP1 interaction mechanistically explains the previously reported repression of nuclear receptor activity by Tax. PMID- 17283139 TI - Interleukin-1beta-driven inflammation promotes the development and invasiveness of chemical carcinogen-induced tumors. AB - The role of microenvironment interleukin 1 (IL-1) on 3-methylcholanthrene (3-MCA) induced carcinogenesis was assessed in IL-1-deficient mice, i.e., IL-1beta(-/-), IL-1alpha(-/-), IL-1alpha/beta(-/-) (double knockout), and mice deficient in the naturally occurring inhibitor of IL-1, the IL-1 receptor antagonist (IL-1Ra). Tumors developed in all wild-type (WT) mice, whereas in IL-1beta-deficient mice, tumors developed slower and only in some of the mice. In IL-1Ra-deficient mice, tumor development was the most rapid. Tumor incidence was similar in WT and IL 1alpha-deficient mice. Histologic analyses revealed fibrotic structures forming a capsule surrounding droplets of the carcinogen in olive oil, resembling foreign body-like granulomas, which appeared 10 days after injection of 3-MCA and persisted until the development of local tumors. A sparse leukocyte infiltrate was found at the site of carcinogen injection in IL-1beta-deficient mice, whereas in IL-1Ra-deficient mice, a dense neutrophilic infiltrate was observed. Treatment of IL-1Ra-deficient mice with recombinant IL-1Ra but not with an inhibitor of tumor necrosis factor abrogated the early leukocytic infiltrate. The late leukocyte infiltrate (day 70), which was dominated by macrophages, was also apparent in WT and IL-1alpha-deficient mice, but was nearly absent in IL-1beta deficient mice. Fibrosarcoma cell lines, established from 3-MCA-induced tumors from IL-1Ra-deficient mice, were more aggressive and metastatic than lines from WT mice; cell lines from IL-1-deficient mice were the least invasive. These observations show the crucial role of microenvironment-derived IL-1beta, rather than IL-1alpha, in chemical carcinogenesis and in determining the invasive potential of malignant cells. PMID- 17283141 TI - Protein phosphatase-1alpha regulates centrosome splitting through Nek2. AB - ATM is a central mediator of the cellular response to the DNA damage produced by ionizing radiation. We recently showed that protein phosphatase 1 (PP1) is activated by ATM. Because Nek2 is activated by autophosphorylation, and because its dephosphorylation is catalyzed by PP1, we asked if the radiation damage signal to Nek2 was mediated by PP1. Overexpression of Nek2 induces premature centrosome splitting probably by phosphorylating centrosome cohesion proteins C Nap1 and Rootletin. In this study, we show isoform specificity of PP1 binding and regulation of Nek2. Although both PP1alpha and PP1gamma coimmunoprecipitated with Nek2, only PP1alpha regulated Nek2 function. Ionizing radiation inhibited Nek2 activity, and this response was dependent on ATM and on PP1 binding to Nek2 and coincident with Thr(320) dephosphorylation of PP1. Radiation-induced inhibition of centrosome splitting was abrogated in cells expressing Nek2 mutated in the PP1 binding motif outside the kinase domain. Conversely, cells depleted of PP1alpha by small interfering RNA showed enhanced centrosome splitting and loss of radiation-induced inhibition of centrosome splitting. The identification of a PP1 specific isoform mediating a checkpoint response opens up the possibility of selectively targeting phosphatases as novel radiation sensitizers. PMID- 17283142 TI - The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer. AB - The transforming growth factor-beta (TGF-beta) signaling pathway has an important role in regulating normal prostate epithelium, inhibiting proliferation, differentiation, and both androgen deprivation-induced and androgen-independent apoptosis. During prostate cancer formation, most prostate cancer cells become resistant to these homeostatic effects of TGF-beta. Although the loss of expression of either the type I (TbetaRI) or type II (TbetaRII) TGF-beta receptor has been documented in approximately 30% of prostate cancers, most prostate cancers become TGF-beta resistant without mutation or deletion of TbetaRI, TbetaRII, or Smads2, 3, and 4, and thus, the mechanism of resistance remains to be defined. Here, we show that type III TGF-beta receptor (TbetaRIII or betaglycan) expression is decreased or lost in the majority of human prostate cancers as compared with benign prostate tissue at both the mRNA and protein level. Loss of TbetaRIII expression correlates with advancing tumor stage and a higher probability of prostate-specific antigen (PSA) recurrence, suggesting a role in prostate cancer progression. The loss of TbetaRIII expression is mediated by the loss of heterozygosity at the TGFBR3 genomic locus and epigenetic regulation of the TbetaRIII promoter. Functionally, restoring TbetaRIII expression in prostate cancer cells potently decreases cell motility and cell invasion through Matrigel in vitro and prostate tumorigenicity in vivo. Taken together, these studies define the loss of TbetaRIII expression as a common event in human prostate cancer and suggest that this loss is important for prostate cancer progression through effects on cell motility, invasiveness, and tumorigenicity. PMID- 17283143 TI - Targeted and nontargeted effects of low-dose ionizing radiation on delayed genomic instability in human cells. AB - All humans receive some radiation exposure and the risk for radiation-induced cancer at low doses is based on the assumption that there is a linear non threshold relationship between dose and subsequent effect. Consequently, risk is extrapolated linearly from high radiation doses to very low doses. However, adaptive responses, bystander effects, and death-inducing effect may influence health effects associated with low-dose radiation exposure. Adaptive response is the phenomenon by which cells irradiated with a sublethal radiation dose can become less susceptible to subsequent high-dose radiation exposure. Bystander effects are nontargeted effects observed in cells that were not irradiated but were either in contact with or received soluble signals from irradiated cells. These non-hit bystander cells can exhibit damage typically associated with direct radiation exposure. Death-inducing effect is a phenomenon whereby medium from human-hamster hybrid cells displaying radiation-induced chromosomal instability is toxic to unirradiated parental cells. In this study, we show that human RKO cells do not exhibit adaptive response, bystander effect, or death-inducing effect, as measured by cell killing, or delayed genomic instability in a stably transfected plasmid-based green fluorescent protein assay measuring homologous recombination and delayed mutation/deletion events. However, growth medium conditioned by some chromosomally unstable RKO derivatives induced genomic instability, indicating that these cells can secrete factor(s) that elicit responses in nonirradiated cells. Furthermore, low radiation doses suppressed the induction of delayed genomic instability by a subsequent high dose, indicative of an adaptive response for radiation-induced genomic instability. These results highlight the inherent variability in cellular responses to low-dose radiation exposure and add to the uncertainties associated with evaluating potential hazards at these low doses. PMID- 17283144 TI - The tumor suppressor activity of the lysyl oxidase propeptide reverses the invasive phenotype of Her-2/neu-driven breast cancer. AB - Expression of the lysyl oxidase gene (LOX) was found to inhibit the transforming activity of the ras oncogene in NIH 3T3 fibroblasts and was hence named the ras recision gene (rrg). Lysyl oxidase (LOX) is synthesized and secreted as a 50-kDa inactive proenzyme (Pro-LOX), which is processed by proteolytic cleavage to a functional 32-kDa enzyme and an 18-kDa propeptide (LOX-PP). Recently, the ras recision activity of the LOX gene in NIH 3T3 cells was mapped to its propeptide region. Here, we show for the first time that LOX-PP inhibits transformation of breast cancer cells driven by Her-2/neu, an upstream activator of Ras. LOX-PP expression in Her-2/neu-driven breast cancer cells in culture suppressed Akt, extracellular signal-regulated kinase, and nuclear factor-kappaB activation. Her 2/neu-induced epithelial to mesenchymal transition was reverted by LOX-PP, as judged by reduced levels of Snail and vimentin; up-regulation of E-cadherin, gamma-catenin, and estrogen receptor alpha; and decreased ability to migrate or to form branching colonies in Matrigel. Furthermore, LOX-PP inhibited Her-2/neu tumor formation in a nude mouse xenograft model. Thus, LOX-PP inhibits signaling cascades induced by Her-2/neu that promote a more invasive phenotype and may provide a novel avenue for treatment of Her-2/neu-driven breast carcinomas. PMID- 17283146 TI - Antiadhesive effects of GRN163L--an oligonucleotide N3'->P5' thio-phosphoramidate targeting telomerase. AB - We determined previously that a novel human telomerase RNA (hTR) antagonist, GRN163L, inhibited the tumorigenic potential of A549-luciferase (A549-luc) lung cancer cells in vitro and in vivo. Further studies revealed that A549-luc cells were also morphologically altered by GRN163L. A549-luc cells treated before cell attachment with a single dose of GRN163L only weakly attached to the substrate and remained rounded, whereas control mismatch-treated cells exhibited typical epitheloid appearance and adhesion properties. These morphologic changes were independent of hTR expression and telomerase inhibition and were unrelated to telomere length. This effect is dependent on the molecular properties of the lipid moiety, the phosphorothioate backbone, and the presence of triplet-G sequences within the GRN163L structure. Altered adhesion was manifested by a 50% reduction in rapid cellular attachment and a 3-fold decrease in total cell spreading surface area. Administration of a single dose of GRN163L (15 mg/kg) at the time of cell inoculation, using an in vivo model of lung cancer metastasis, resulted in significant reductions in tumor burden at days 13, 20, and 27 of tumor progression. Thus, the potent antimetastatic effects of GRN163L may be related, in part, to the antiadhesive effects of this novel cancer therapeutic conferred via specific structural determinants and that these effects are independent of telomerase inhibition or telomere shortening. PMID- 17283145 TI - Growth factor stimulation reduces residual quiescent chronic myelogenous leukemia progenitors remaining after imatinib treatment. AB - The BCR/ABL tyrosine kinase inhibitor imatinib mesylate is highly effective in the treatment of chronic myelogenous leukemia (CML) but fails to eliminate all leukemia cells. Residual leukemia stem and progenitor cells persist in imatinib responsive patients and may be a potential source of relapse. Previous studies indicate that imatinib preferentially targets dividing cells, and nondividing progenitor cells are resistant to imatinib-mediated apoptosis. We investigated whether growth factor stimulation of progenitor proliferation could reduce the number of residual nondividing cells remaining after imatinib treatment. CML and normal CD34(+) cells were labeled with 5-(and 6-)-carboxyfluorescein diacetate succinimidyl ester (CFSE) to track cell division and cultured in low or high concentrations of growth factor to determine effects of growth factor stimulation on nondividing cells. High growth factor concentrations significantly enhanced CML proliferation with or without imatinib treatment and significantly reduced the number of viable, nondividing CFSE bright cells remaining after imatinib exposure. Stimulation with high growth factor before imatinib treatment further reduced the number of residual nondividing CML CD34(+) cells. Importantly, clinically achievable concentrations of granulocyte macrophage colony-stimulating factor alone or in combination with granulocyte colony-stimulating factor also significantly reduced nondividing CML CD34(+) cells. These results support the potential efficacy of growth factor stimulation in reducing the residual leukemia progenitor population in imatinib-treated patients. PMID- 17283147 TI - Ability to acquire drug resistance arises early during the tumorigenesis process. AB - Resistance to chemotherapy is one of the principal causes of cancer mortality and is generally considered a late event in tumor progression. Although cellular models of drug resistance have been useful in identifying the molecules responsible for conferring drug resistance, most of these cellular models are derived from cell lines isolated from patients at a late stage in cancer progression. To ask at which stage in the tumorigenic progression does the cell gain the ability to acquire drug resistance, we generated a series of pre tumorigenic and tumorigenic cells from human embryonic skin fibroblasts by introducing, sequentially, the catalytic subunit of telomerase, SV40 large T and small T oncoproteins, and an oncogenic form of ras. We show that the ability to acquire multidrug resistance (MDR) can arise before the malignant transformation stage. The minimal set of changes necessary to obtain pre-tumorigenic drug resistant cells is expression of telomerase and inactivation of p53 and pRb. Thus, the pathways inactivated during tumorigenesis also confer the ability to acquire drug resistance. Microarray and functional studies of drug-resistant pre tumorigenic cells indicate that the drug efflux pump P-glycoprotein is responsible for the MDR phenotype in this pre-tumorigenic cell model. PMID- 17283148 TI - In vivo real-time tracking of single quantum dots conjugated with monoclonal anti HER2 antibody in tumors of mice. AB - Studies with tracking of single nanoparticles are providing new insights into the interactions and processes involved in the transport of drug carriers in living mice. Here, we report the tracking of a single particle quantum dot (Qdot) conjugated with tumor-targeting antibody in tumors of living mice using a dorsal skinfold chamber and a high-speed confocal microscope with a high-sensitivity camera. Qdot labeled with the monoclonal anti-HER2 antibody was injected into mice with HER2-overexpressing breast cancer to analyze the molecular processes of its mechanistic delivery to the tumor. Movement of single complexes of the Qdot antibody could be clearly observed at 30 frames/s inside the tumor through a dorsal skinfold chamber. We successfully identified six processes of delivery: initially in the circulation within a blood vessel, during extravasation, in the extracelullar region, binding to HER2 on the cell membrane, moving from the cell membrane to the perinuclear region, and in the perinuclear region. The six processes were quantitatively analyzed to understand the rate-limiting constraints on Qdot-antibody delivery. The movement of the complexes at each stage was "stop-and-go." The image analysis of the delivery processes of single particles in vivo provides valuable information on antibody-conjugated therapeutic nanoparticles, which will be useful in increasing therapeutic efficacy. PMID- 17283149 TI - Prevention of mantle lymphoma tumor establishment by routing transferrin receptor toward lysosomal compartments. AB - Mantle cell lymphoma (MCL) is one of the most frequent of the newly recognized non-Hodgkin's lymphomas. The major problem of MCL therapy is the occurrence of relapse and subsequent resistance to chemotherapy and immunotherapy in virtually all cases. Here, we show that one injection of anti-human transferrin receptor (TfR) monoclonal antibody A24 totally prevented xenografted MCL tumor establishment in nude mice. It also delayed and inhibited tumor progression of established tumors, prolonging mice survival. In vitro, A24 induced up to 85% reduction of MCL cell proliferation (IC(50) = 3.75 nmol/L) independently of antibody aggregation, complement-dependent or antibody-dependent cell-mediated cytotoxicity. A24 induced MCL cell apoptosis through caspase-3 and caspase-9 activation, either alone or synergistically with chemotherapeutic agents. A24 induced TfR endocytosis via the clathrin adaptor protein-2 complex pathway followed by transport to lysosomal compartments. Therefore, A24-based therapies alone or in association with classic chemotherapies could provide a new alternative strategy against MCL, particularly in relapsing cases. PMID- 17283150 TI - Insulin-like growth factor-I receptor signaling blockade combined with radiation. AB - Signaling through the insulin-like growth factor-I receptor (IGF-IR) is implicated in cellular proliferation, apoptosis, carcinogenesis, metastasis, and resistance to cytotoxic cancer therapies. Targeted disruption of IGF-IR signaling combined with cytotoxic therapy may therefore yield improved anticancer efficacy over conventional treatments alone. In this study, a fully human anti-IGF-IR monoclonal antibody A12 (ImClone Systems, Inc., New York, NY) is examined as an adjunct to radiation therapy. IGF-IR expression is shown for a diverse cohort of cell lines, whereas targeted IGF-IR blockade by A12 inhibits IGF-IR phosphorylation and activation of the downstream effectors Akt and mitogen activated protein kinase. Anchorage-dependent proliferation and xenograft growth is inhibited by A12 in a dose-dependent manner, particularly for non-small cell lung cancer lines. Clonogenic radiation survival of H226 and H460 cells grown under anchorage-dependent conditions is impaired by A12, demonstrating a radiation dose-enhancing effect for IGF-IR blockade. Postradiation anchorage independent colony formation is inhibited by A12 in A549 and H460 cells. In the H460 xenograft model, combining A12 and radiation significantly enhances antitumor efficacy compared with either modality alone. These effects may be mediated by promotion of radiation-induced, double-stranded DNA damage and apoptosis as observed in cell culture. In summary, these results validate IGF-IR signal transduction blockade as a promising strategy to improve radiation therapy efficacy in human tumors, forming a basis for future clinical trials. PMID- 17283151 TI - p53 enhances gefitinib-induced growth inhibition and apoptosis by regulation of Fas in non-small cell lung cancer. AB - Treatment with gefitinib, a specific inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), has resulted in dramatic responses in some patients with non-small cell lung cancer (NSCLC). Most patients who respond to gefitinib have EGFR-TK mutations; however, >10% of patients with EGFR-TK mutations do not respond. Similarly, some patients without EGFR-TK mutations respond to this drug, suggesting that other factors determine sensitivity to gefitinib. Aberrations of the tumor suppressor gene p53 are frequently associated with drug resistance. In this study, we investigated the role of p53 in growth inhibitory and apoptotic effects of gefitinib in the human NSCLC cell lines NCI H1299 and A549, which have no EGFR-TK mutations. NCI-H1299 cells, which had a p53 null genotype, were more resistant to gefitinib compared with A549 cells, which were wild-type p53 (IC(50), 40 micromol/L in NCI-H1299 and 5 micromol/L in A549). Treatment of A549 with gefitinib resulted in the translocation of p53 from cytosol to nucleus and the up-regulation of Fas, which was localized to the plasma membrane. In the stable H1299 cell line with tetracycline-inducible p53 expression, induced p53 enhanced growth inhibition and apoptosis by gefitinib through the up-regulation of Fas and restoration of caspase activation. A caspase inhibitor, Z-VAD-fmk, reduced these effects. Conversely, inhibition of p53 using antisense oligonucleotide in A549 caused a significant decrease in apoptosis by gefitinib and down-regulation of Fas under the same conditions. In conclusion, p53 may play a role in determining gefitinib sensitivity by regulating Fas expression in NSCLC. PMID- 17283152 TI - Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers. AB - Trastuzumab antitumor activity in ErbB2-overexpressing breast cancers seems to be dependent upon the presence of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a phosphatase that dampens phosphatidylinositol 3-kinase Akt signaling. Consequently, PTEN deficiency, which occurs in 50% of breast cancers, predicts for resistance to trastuzumab monotherapy. Here, we show that lapatinib, a small-molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, exerts its antitumor activity in a PTEN-independent manner. Steady-state phosphorylated ErbB2 (p-ErbB2) and p-Akt (S473) protein levels were inhibited within 30 min following lapatinib but not in response to trastuzumab in BT474 and Au565 cells (two ErbB2-overexpressing breast cancer cell lines that are sensitive to the proapoptotic effects of lapatinib). Whereas trastuzumab reportedly inhibits SRC phosphorylation (Y416), which in turn reduced SRC-ErbB2 protein interactions, lapatinib had no effect on either variable. To assess the potential functional role that PTEN might play in lapatinib antitumor activity, we selectively knocked down PTEN in BT474 and Au565 cells using small interfering RNA transfection. Loss of PTEN did not affect induction of tumor cell apoptosis by lapatinib in either cell line. In addition, lapatinib inhibited Akt phosphorylation in MDA-MB-468 cells, an ErbB1-expressing/ErbB2 non-overexpressing breast cancer line, despite their PTEN-null status. Moreover, patients with ErbB2-overexpressing inflammatory breast cancers responded to lapatinib monotherapy regardless of PTEN status. Thus, lapatinib seems to exert its antitumor activity in ErbB2-overexpressing breast cancers in a PTEN-independent manner. These data emphasize the importance of assessing PTEN status in tumors when selecting ErbB2-targeted therapies in patients with breast cancer. PMID- 17283153 TI - Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. AB - ABT-737 is a novel and potent Bcl-2 antagonist with single-agent activity against small-cell lung cancer (SCLC) cell lines. Here, we evaluated the contribution of Bcl-2 family members to the in vitro cellular response of several SCLC cell lines to ABT-737. Relatively higher levels of Bcl-2, Bcl-X(L), Bim and Noxa, and lower levels of Mcl-1 characterized naive SCLC cell lines that were sensitive to ABT 737. Conversely, a progressive decrease in the relative levels of Bcl-2 and Noxa and a progressive increase in Mcl-1 levels characterized the increased resistance of H146 cells following chronic exposure to ABT-737. Knockdown of Mcl-1 with small interfering RNA sensitized two resistant SCLC cell lines H196 and DMS114 to ABT-737 by enhancing the induction of apoptosis. Likewise, up-regulation of Noxa sensitized H196 cells to ABT-737. Combination treatment with DNA-damaging agents was extremely synergistic with ABT-737 and was associated with the down regulation of Mcl-1 and the up-regulation of Noxa, Puma, and Bim in H196 cells. Thus, SCLC cells sensitive to ABT-737 expressed the target proteins Bcl-2 and Bcl X(L), whereas Mcl-1 and factors regulating Mcl-1 function seem to contribute to the overall resistance of SCLC cells to ABT-737. Overall, these observations provide further insight as to the mechanistic bases for ABT-737 efficacy in SCLC and will be helpful for profiling patients and aiding in the rational design of combination therapies. PMID- 17283154 TI - A single-chain Fv diabody against human leukocyte antigen-A molecules specifically induces myeloma cell death in the bone marrow environment. AB - Cross-linked human leukocyte antigen (HLA) class I molecules have been shown to mediate cell death in neoplastic lymphoid cells. However, clinical application of an anti-HLA class I antibody is limited by possible side effects due to widespread expression of HLA class I molecules in normal tissues. To reduce the unwanted Fc-mediated functions of the therapeutic antibody, we have developed a recombinant single-chain Fv diabody (2D7-DB) specific to the alpha2 domain of HLA A. Here, we show that 2D7-DB specifically induces multiple myeloma cell death in the bone marrow environment. Both multiple myeloma cell lines and primary multiple myeloma cells expressed HLA-A at higher levels than normal myeloid cells, lymphocytes, or hematopoietic stem cells. 2D7-DB rapidly induced Rho activation and robust actin aggregation that led to caspase-independent death in multiple myeloma cells. This cell death was completely blocked by Rho GTPase inhibitors, suggesting that Rho-induced actin aggregation is crucial for mediating multiple myeloma cell death. Conversely, 2D7-DB neither triggered Rho mediated actin aggregation nor induced cell death in normal bone marrow cells despite the expression of HLA-A. Treatment with IFNs, melphalan, or bortezomib enhanced multiple myeloma cell death induced by 2D7-DB. Furthermore, administration of 2D7-DB resulted in significant tumor regression in a xenograft model of human multiple myeloma. These results indicate that 2D7-DB acts on multiple myeloma cells differently from other bone marrow cells and thus provide the basis for a novel HLA class I-targeting therapy against multiple myeloma. PMID- 17283156 TI - Evidence that tumor necrosis factor-related apoptosis-inducing ligand induction by 5-Aza-2'-deoxycytidine sensitizes human breast cancer cells to adriamycin. AB - The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) inhibits DNA methyltransferase activity and sensitizes cancer cells to chemotherapy, but the mechanisms of its sensitization are not fully understood. Here, we show that 5-aza-CdR induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the human breast cancer MDA-231 cells. Induction of TRAIL by 5-aza-CdR correlated with inactivation of Akt. Furthermore, we show that overexpression of the active form of Akt by adenovirus infection or inhibition of the Akt downstream target glycogen synthase kinase 3 by its pharmacologic inhibitors abolishes TRAIL induction by 5-aza-CdR. Importantly, we show that the combined treatment of breast cancer cells with 5-aza-CdR and Adriamycin significantly increases apoptotic cell death compared with the treatment with either agent alone. Moreover, the combined treatment activated both death receptor and mitochondrial apoptotic pathways, whereas Adriamycin alone activated only the mitochondrial pathway while 5-aza-CdR failed to activate either. More importantly, down-regulation of TRAIL by small interference RNA silencing decreased 5-aza-CdR-mediated Adriamycin-induced caspase activation and apoptosis, thus conferring Adriamycin resistance. Taken together, our results suggest that induction of TRAIL by 5-aza-CdR is critical for enhancing chemosensitivity of breast cancer cells to Adriamycin. PMID- 17283155 TI - Bcl-2 protects endothelial cells against gamma-radiation via a Raf-MEK-ERK survivin signaling pathway that is independent of cytochrome c release. AB - The Bcl-2 oncoprotein is a potent inhibitor of apoptosis and is overexpressed in a wide variety of malignancies. Until recently, it was generally accepted that Bcl-2 primarily mediates its antiapoptotic function by regulating cytochrome c release from mitochondria. However, more recent studies have shown that Bcl-2 is present on several intracellular membranes and mitochondria may not be the only site where Bcl-2 exercises its survival function. In this study, we investigated if Bcl-2 can protect endothelial cells against gamma-radiation by a cytochrome c independent signaling pathway. Human dermal microvascular endothelial cells (HDMEC), when exposed to gamma-radiation, exhibited a time-dependent activation of caspase-3 that was associated with increased cytochrome c release from mitochondria. Bcl-2 expression in endothelial cells (HDMEC-Bcl-2) significantly inhibited irradiation-induced caspase-3 activation. However, Bcl-2-mediated inhibition of caspase-3 was significantly reversed by inhibition of the Raf mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway. Interestingly, caspase-3 activation in HDMEC-Bcl 2 cells was not associated with cytochrome c release. We also observed that endothelial cell Bcl-2 expression significantly increased the expression of survivin and murine double minute-2 (Mdm2) via the Raf-MEK-ERK pathway. Endothelial cells expressing Bcl-2 also inhibited gamma-radiation-induced activation of p38 MAPK and p53 accumulation. Inhibition of p53 accumulation in HDMEC-Bcl-2 could be due to the enhanced expression of Mdm2 in these cells. Taken together, these results show three mechanisms by which Bcl-2 may mediate endothelial cell cytoprotection independently of cytochrome c release: (a) increased survivin expression, (b) inhibition of p53 accumulation, and (c) inhibition of p38 MAPK. PMID- 17283157 TI - Sensitizing effect of galectin-7 in urothelial cancer to cisplatin through the accumulation of intracellular reactive oxygen species. AB - To improve chemotherapeutic efficacy in urothelial cancer, it is important to identify predictive markers for chemosensitivity as well as possible molecules accelerating cell killing mechanisms. In this study, we assessed the possibility of galectin-7 to accelerate cis-diamminedichloroplatinum (CDDP)-induced cell killing in vitro and also to predict chemosensitivity against CDDP in urothelial cancer patients. The expression of galectin-7 was analyzed in five bladder cancer cell lines with different p53 status after treatment with CDDP. The roles of galectin-7 in chemosensitivity against CDDP were analyzed by transfection of the galectin-7 gene into several of these cell lines. Furthermore, the relationship between the expression of galectin-7 and the response to neoadjuvant chemotherapy was analyzed in 17 human bladder cancer specimens. Exposure to CDDP induced galectin-7 in cell lines with wild-type p53 but not in those with mutated p53. When the galectin-7 gene was transfected into cell lines with mutated p53, the sensitivity to CDDP increased compared with control transfectants. In addition, galectin-7-transfected cells exhibited more accumulation of intracellular reactive oxygen species and activation of c-Jun NH(2)-terminal kinase (JNK) and Bax than control transfectants. SP600125, an inhibitor of JNK, or antioxidant N acetyl-L-cysteine inhibited the enhancement of chemosensitivity against CDDP by galectin-7 transfection. In clinical samples, the expression levels of galectin-7 were significantly lower in urothelial carcinomas compared with normal urothelium. When chemosensitivity was tested, its expression levels were higher in the chemosensitive group than in the chemoresistant group. Galectin-7 is a candidate for a predictive marker of chemosensitivity against CDDP, and the targeted expression of galectin-7 might overcome the chemoresistance of urothelial cancer. PMID- 17283158 TI - HIV protease inhibitor nelfinavir inhibits growth of human melanoma cells by induction of cell cycle arrest. AB - HIV protease inhibitors (HIV PI) are a class of antiretroviral drugs that are designed to target the viral protease. Unexpectedly, this class of drugs is also reported to have antitumor activity. In this study, we have evaluated the in vitro activity of nelfinavir, a HIV PI, against human melanoma cells. Nelfinavir inhibits the growth of melanoma cell lines at low micromolar concentrations that are clinically attainable. Nelfinavir promotes apoptosis and arrests cell cycle at G(1) phase. Cell cycle arrest is attributed to inhibition of cyclin-dependent kinase 2 (CDK2) and concomitant dephosphorylation of retinoblastoma tumor suppressor. We further show that nelfinavir inhibits CDK2 through proteasome dependent degradation of Cdc25A phosphatase. Our results suggest that nelfinavir is a promising candidate chemotherapeutic agent for advanced melanoma, for which novel and effective therapies are urgently needed. PMID- 17283159 TI - Erlotinib directly inhibits HER2 kinase activation and downstream signaling events in intact cells lacking epidermal growth factor receptor expression. AB - Erlotinib (Tarceva), is an orally available, reversible inhibitor of epidermal growth factor receptor (EGFR; HER1) that exhibits inhibitory activity on purified HER2 kinase at much higher concentrations. Despite the minimal activity on purified protein in vitro, in vivo studies show that erlotinib inhibits the growth of HER2-driven systems effectively. Several hypotheses have been put forward to explain this discrepancy. In particular, it has been suggested that erlotinib might indirectly suppress the activity of HER2 by blocking the ability of EGFR to transactivate it when the two receptors are part of a heterodimer complex. However, an alternative possibility that has not been adequately addressed is whether the direct inhibitory action of erlotinib on the HER2 kinase might account for the observed biological responses. To distinguish between a direct effect of erlotinib on HER2 kinase in intact cells or an indirect effect of erlotinib on HER2 activity that is mediated through EGFR, we generated cell lines that express either EGFR-H2 chimeric receptor or HER2 and HER3 receptors in an EGFR-negative background. We show that dose-dependent inhibition of HER2 was achieved at the receptor level, on downstream signaling molecules, and more importantly was also translated into inhibition of cell growth. Our findings imply that the inhibitory effect of erlotinib in HER2-expressing cells may in part be mediated through direct interaction with HER2 rather than indirectly through a process that requires the presence of EGFR. PMID- 17283160 TI - TSP50 encodes a testis-specific protease and is negatively regulated by p53. AB - Earlier studies suggested that TSP50 is a testis-specific gene that encodes a protein, which is homologous to serine proteases but differs in that threonine replaces serine in its catalytic triad. Most importantly, it was abnormally reactivated in many breast cancer biopsies tested. While further investigating its biochemical and cell biological natures, we found that TSP50 exhibited enzyme activity and was located in the endoplasmic reticulum and cytosol membrane. During our studies to elucidate the regulatory mechanisms related to its differential expression, we discovered a putative p53-binding site and several Sp1-binding sites in the TSP50 promoter, which led us to test if it was regulated by the p53 gene. We found that the p53 transgene negatively regulated the TSP50 promoter in diverse types of cell lines. This result was consistent with other observations: (a) p53 overexpression reduced endogenous TSP50 expression; and (b) breast cancer cell lines containing mutated p53, such as MCF7/Adr, or normal p53, such as MCF7, produced high or low levels of TSP50 transcripts, which was consistent with the fact that TSP50 promoter activity was much higher in MCF7/Adr than that in MCF7 cells. We also found that the quantity of Sp1 transcription factor was lower in MCF7/Adr than in MCF7 cells, which suggested that another mechanism (i.e., transcription factor modulation) was also involved in TSP50 differential expression. PMID- 17283162 TI - A small-molecule enhancer of signal transducer and activator of transcription 1 transcriptional activity accentuates the antiproliferative effects of IFN-gamma in human cancer cells. AB - The transcription factor signal transducer and activator of transcription (STAT) 1 can mediate antiproliferative and proapoptotic effects in cancer cells, and a number of mechanisms have been found whereby STAT1 signaling is attenuated in tumors thereby increasing their malignant behavior. Thus, enhancing gene transcription mediated by STAT1 may be an effective approach to cancer therapy. A high-throughput screen was developed to identify molecules that could enhance STAT1-dependent gene expression. Through this approach, it was found that 2-(1,8 naphthyridin-2-yl)phenol (2-NP) caused a 2-fold increase in STAT1-dependent reporter gene expression compared with that seen with maximally effective concentrations of IFN-gamma alone. This effect was specific to STAT1 because 2-NP had no effect on unrelated transcription factors such as nuclear factor (NF) kappaB or the highly homologous transcription factor STAT3. STAT1-dependent gene activation was enhanced by this compound in a variety of human and murine cell lines and was independent of the stimulus used. Furthermore, 2-NP enhanced the expression of the bona fide endogenous STAT1 target gene interferon regulatory factor 1. 2-NP increased the duration of STAT1 tyrosine phosphorylation in response to IFN-gamma, and this may underlie its enhancement of STAT1-dependent transcription. Reflecting the fact that STAT1 can exert tumor-suppressive effects, 2-NP enhanced the ability of IFN-gamma to inhibit the proliferation of human breast cancer and fibrosarcoma cells. Tumor cells lacking STAT1 were unaffected by either IFN-gamma or 2-NP. These findings indicate that enhancement of STAT1 transcriptional activity may have utility in anticancer therapies, and that cell-based screens for modulators of transcription factor function can be a useful approach for drug discovery. PMID- 17283161 TI - Low-dose irradiation of nontransformed cells stimulates the selective removal of precancerous cells via intercellular induction of apoptosis. AB - An important stage in tumorigenesis is the ability of a precancerous cell to escape natural anticancer signals imposed on it by neighboring cells and its microenvironment. We have previously characterized a system of intercellular induction of apoptosis whereby nontransformed cells selectively remove transformed cells from coculture via cytokine and reactive oxygen/nitrogen species (ROS/RNS) signaling. We report that irradiation of nontransformed cells with low doses of either high linear energy transfer (LET) alpha-particles or low LET gamma-rays leads to stimulation of intercellular induction of apoptosis. The use of scavengers and inhibitors confirms the involvement of ROS/RNS signaling and of the importance of transformed cell NADPH oxidase in the selectivity of the system. Doses as low as 2-mGy gamma-rays and 0.29-mGy alpha-particles were sufficient to produce an observable increase in transformed cell apoptosis. This radiation-stimulated effect saturates at very low doses (50 mGy for gamma-rays and 25 mGy for alpha-particles). The use of transforming growth factor-beta (TGF beta) neutralizing antibody confirms a role for the cytokine in the radiation induced signaling. The system may represent a natural anticancer mechanism stimulated by extremely low doses of ionizing radiation. PMID- 17283163 TI - Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cells. AB - Fatty acid synthase (FAS), the cellular enzyme that synthesizes palmitate, is expressed at high levels in tumor cells and is vital for their survival. Through the synthesis of palmitate, FAS primarily drives the synthesis of phospholipids in tumor cells. In this study, we tested the hypothesis that the FAS inhibitors induce endoplasmic reticulum (ER) stress in tumor cells. Treatment of tumor cells with FAS inhibitors induces robust PERK-dependent phosphorylation of the translation initiation factor eIF2alpha and concomitant inhibition of protein synthesis. PERK-deficient transformed mouse embryonic fibroblasts and HT-29 colon carcinoma cells that express a dominant negative PERK (DeltaC-PERK) are hypersensitive to FAS inhibitor-induced cell death. Pharmacologic inhibition of FAS also induces the processing of X-box binding protein-1, indicating that the IRE1 arm of the ER stress response is activated when FAS is inhibited. Induction of ER stress is further confirmed by the increased expression of the ER stress regulated genes CHOP, ATF4, and GRP78. FAS inhibitor-induced ER stress is activated prior to the detection of caspase 3 and PARP cleavage, primary indicators of cell death, whereas orlistat-induced cell death is rescued by coincubation with the global translation inhibitor cycloheximide. Lastly, FAS inhibitors cooperate with the ER stress inducer thapsigargin to enhance tumor cell killing. These results provide the first evidence that FAS inhibitors induce ER stress and establish an important mechanistic link between FAS activity and ER function. PMID- 17283164 TI - Development of rituximab-resistant lymphoma clones with altered cell signaling and cross-resistance to chemotherapy. AB - Immunotherapy with rituximab (chimeric anti-CD20 monoclonal antibody, Rituxan), alone or in conjunction with chemotherapy, has significantly improved the treatment outcome of lymphoma patients. Via an elusive mechanism, a subpopulation of patients becomes unresponsive and/or relapses. To recapitulate various aspects of acquired resistance, rituximab-resistant (RR) clones were established from lymphoma lines and compared with parental cells. Surface CD20 expression was diminished in the clones. The clones neither responded to rituximab-mediated growth reduction or complement-dependent cytotoxicity nor underwent apoptosis in response to cross-linked rituximab. Rituximab failed to chemosensitize the RR clones, which exhibited constitutive hyperactivation of the nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 pathways, leading to overexpression of B-cell lymphoma protein 2 (Bcl-2), Bcl-2-related gene (long alternatively spliced variant of Bcl-x gene), and myeloid cell differentiation 1 and higher drug resistance. Unlike parental cells, rituximab neither inhibited the activity of these pathways nor diminished the expression of resistant factors. Pharmacologic inhibitors of the survival pathways or Bcl-2 family members reduced the activity of these pathways, diminished antiapoptotic protein expression, and chemosensitized the RR clones. These novel in vitro results denote that continuous long-term rituximab exposure culminates in RR clones that do not respond to rituximab-mediated effects, have altered cellular signaling dynamics, and exhibit different genetic and phenotypic properties compared with parental cells. The data also reveal that although RR clones exhibit higher resistance to rituximab and cytotoxic drugs, these clones can be chemosensitized following treatment with pharmacologic inhibitors (e.g., dehydroxymethylepoxyquinomicin, bortezomib, PD098059) that target survival/antiapoptotic pathways. The findings also identify intracellular targets for potential molecular therapeutic intervention to increase treatment efficacy. The significance and potential clinical relevance of the findings are discussed. PMID- 17283166 TI - Depleting intratumoral CD4+CD25+ regulatory T cells via FasL protein transfer enhances the therapeutic efficacy of adoptive T cell transfer. AB - One strategy for improving adoptive therapy is preconditioning the host immune environment by depleting CD4(+)CD25(+) regulatory T cells (Treg) suppressive to antitumor responses. Given that Treg increase, or selectively accumulate, within tumors and are sensitive to FasL-mediated apoptosis, we test here the hypothesis that inducing apoptosis of intratumoral Treg using FasL may improve adoptive T cell therapy. We show that FasL applied intratumorally via protein transfer decreases intratumoral Treg via inducing apoptosis in these cells. Significantly, we show that the use of FasL prior to the infusion of tumor-reactive CD8(+) T cells enhances the therapeutic efficacy of adoptive T cell transfer against established tumors, which is mediated by persistent, systemic antitumor immunity. Intratumoral FasL protein transfer also results in neutrophil infiltration of tumor. However, we show that intratumoral immunodepletion of neutrophils does not abolish the effect of FasL on adoptive transfer. Rather, the effect of FasL is completely abolished by cotransfer of Treg, isolated from the tumor-draining lymph nodes. Hence, our study shows for the first time that using FasL to predeplete intratumoral Treg provides a useful means for optimizing adoptive therapy. PMID- 17283165 TI - Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase. AB - Tamoxifen is an anticancer drug that induces oxidative stress and apoptosis via mitochondria-dependent and nitric oxide (NO)-dependent pathways. The present report shows that tamoxifen increases intramitochondrial ionized Ca(2+) concentration and stimulates mitochondrial NO synthase (mtNOS) activity in the mitochondria from rat liver and human breast cancer MCF-7 cells. By stimulating mtNOS, tamoxifen hampers mitochondrial respiration, releases cytochrome c, elevates mitochondrial lipid peroxidation, increases protein tyrosine nitration of certain mitochondrial proteins, decreases the catalytic activity of succinyl CoA:3-oxoacid CoA-transferase, and induces aggregation of mitochondria. The present report suggests a critical role for mtNOS in apoptosis induced by tamoxifen. PMID- 17283167 TI - Modulation of telomerase promoter tumor selectivity in the context of oncolytic adenoviruses. AB - The telomerase RNA (hTR) and reverse transcriptase (hTERT) promoters are active in most cancer cells, but not in normal cells, and are useful for transcriptional targeting in gene therapy models. Telomerase-specific conditionally replicating adenoviruses (CRAd) are attractive vectors because they should selectively lyse tumor cells. Here, we compare CRAds, in which either the hTR or hTERT promoter controls expression of the adenovirus E1A gene. In replication-defective reporter adenoviruses, the hTR promoter was up to 57-fold stronger in cancer cells than normal cells and up to 49-fold stronger than hTERT. In normal cells, hTERT promoter activity was essentially absent. Doses of telomerase-specific CRAds between 1.8 and 28 infectious units per cell efficiently killed cancer cells, but normal cells required higher doses. However, CRAd DNA replication and E1A expression were detected in both cancer and normal cells. Overall, tumor specificity of the CRAds was limited compared with nonreplicating vectors. Surprisingly, both CRAds expressed similar E1A levels and functional behavior, despite known differentials between hTR and hTERT promoter activities, suggesting that the promoters are deregulated. Rapid amplification of cDNA ends analysis of hTR-/hTERT-E1A transcripts ruled out cryptic transcription from the vector backbone. Blocking E1A translation partially restored the hTR-/hTERT-E1A mRNA differential, evidencing feedback regulation by E1A. PMID- 17283168 TI - p53 short peptide (p53pep164) regulates lipopolysaccharide-induced tumor necrosis factor-alpha factor/cytokine expression. AB - The p53 protein is a sequence-specific DNA-binding factor that can induce apoptosis or activate genes whose dysregulation is involved in cancer. By using serial analysis of gene expression technique, p53-induced genes (PIGs) have been identified, one of which was lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) factor (LITAF/PIG7). LITAF regulates the transcription of cytokines such as TNF-alpha. To further elucidate the role of p53 in LITAF expression, LITAF promoter activity was carefully dissected. In this study, we found that the element required for transcriptional activity is mainly located in the region from -990 to -500 of the LITAF promoter; the specific site required for p53 protein-DNA binding is located between -550 and -500. We also found that transient transfection of either a p53 short DNA sequence, called p53LFB12, or its corresponding 7-amino-acid synthetic peptide from amino acids 164 to 170 (K164Q165S166Q167H168M169T170), named p53pep164, significantly reduced LITAF promoter activity to 15% in p53-null H1299 cells. Transfection of p53pep164 into H1299 cells significantly down-regulated LPS-induced LITAF expression as well. Furthermore, transfection of p53pep164 into human monocytes resulted in down regulation of nine proinflammatory cytokines, including TNF-alpha. We also found that the LPS-activated p53 is a short-lived protein, and that p53-orchestrated apoptosis occurs shortly after the initiation stage following LPS stimulation and lasts a short time. Once p53 levels return to baseline, the p53-mediated inhibition of LITAF is released, and LITAF-mediated cytokine production can proceed. The present finding proposes a novel link between p53 and the inflammatory processes and highlights potential interventional approaches to control p53-associated inflammatory processes. PMID- 17283169 TI - DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells. AB - Although natural killer (NK) cells are well known for their ability to kill tumors, few studies have addressed the interactions between resting (nonactivated) NK cells and freshly isolated human tumors. Here, we show that human leukocyte antigen class I(low) tumor cells isolated directly from patients with advanced ovarian carcinoma trigger degranulation by resting allogeneic NK cells. This was paralleled by induction of granzyme B and caspase-6 activities in the tumor cells and significant tumor cell lysis. Ovarian carcinoma cells displayed ubiquitous expression of the DNAX accessory molecule-1 (DNAM-1) ligand PVR and sparse/heterogeneous expression of the NKG2D ligands MICA/MICB and ULBP1, ULBP2, and ULBP3. In line with the NK receptor ligand expression profiles, antibody-mediated blockade of activating receptor pathways revealed a dominant role for DNAM-1 and a complementary contribution of NKG2D signaling in tumor cell recognition. These results show that resting NK cells are capable of directly recognizing freshly isolated human tumor cells and identify ovarian carcinoma as a potential target for adoptive NK cell-based immunotherapy. PMID- 17283171 TI - Microscopic intratumoral dosimetry of radiolabeled antibodies is a critical determinant of successful radioimmunotherapy in B-cell lymphoma. AB - Radioimmunotherapy is a highly effective treatment for some hematologic malignancies; however, the underlying mechanisms of tumor clearance remain poorly understood. We have previously shown that both targeted radiation using (131)I labeled anti-MHC class II (MHCII) monoclonal antibody (mAb) plus mAb signaling with unlabeled anti-idiotype are required for the long-term clearance of tumor in syngeneic murine lymphoma models. In this study, we have investigated how the microdistribution of the targeted radiation component of this combination affects the long-term clearance of lymphoma. (131)I-labeled mAb targeting CD45 and MHCII antigens was found to deliver similar doses of radiation to tumor-bearing organ using conventional dosimetry ( approximately 1.0 Gy per MBq when (131)I was labeled to 500 mug mAb and given i.v. per mouse), but when used as radiation vectors in combination therapy only, (131)I-anti-MHCII plus anti-idiotype produced long-term survival. The profound differences in therapy did not seem to be dependent on levels of (131)I-mAb tumor-binding or antibody-dependent cytotoxicity. Instead, the microscopic intratumoral dosimetry seemed to be critical with the (131)I-anti-MHCII, delivering more concentrated and therefore substantially higher radiation dose to tumor cells. When the administered activity of (131)I-anti-CD45 was increased, a radiation dose response was shown in the presence of anti-idiotype and long-term survival was seen. We believe that these new insights should influence the selection of new antigen targets and the design of dosimetric methods in radioimmunotherapy of lymphoma. PMID- 17283170 TI - Peptide vaccine given with a Toll-like receptor agonist is effective for the treatment and prevention of spontaneous breast tumors. AB - Our goal is to develop peptide vaccines that stimulate tumor antigen-specific T cell responses against frequently found cancers. Previous work has shown that to generate effective T-cell responses, peptides have to be administered in combination with strong adjuvants such as Toll-like receptor agonists. However, most animal tumor model systems used to study peptide vaccines were not truly representative of malignant diseases in humans because they solely used transplantable tumor lines, and instead of true tumor antigens, they used highly immunogenic foreign proteins. Here, we describe a peptide vaccination strategy, which is highly effective in delaying or preventing the occurrence of spontaneous breast tumors. Transgenic female BALB-neuT mice that carry the activated rat HER 2/neu oncogene were vaccinated with a synthetic peptide from the rat HER-2/neu gene product, which represents an epitope for CTLs in combination with a Toll like receptor agonist adjuvant. Our results show that to obtain tumor antigen specific CTL responses and antitumor effects, the vaccine had to be administered repetitively, or the function of CD4/CD25 T regulatory cells had to be blocked with anti-CD25 antibody therapy. Mice that were vaccinated with this approach remained tumor-free or were able to control spontaneous tumor growth and exhibited long-lasting CTL responses, not only against the immunizing peptide but also against other peptides derived from rat HER-2/neu product (i.e., epitope spreading). These results suggest that similar strategies should be followed for conducting clinical studies in patients. PMID- 17283172 TI - In vivo effects of vaccination with six-transmembrane epithelial antigen of the prostate: a candidate antigen for treating prostate cancer. AB - Immunotherapy may provide an alternative treatment for cancer patients, especially when tumors overexpress antigens that can be recognized by immune cells. The identification of markers and therapeutic targets that are up regulated in prostate cancer has been important to design new potential treatments for prostate cancer. Among them, the recently identified six transmembrane epithelial antigen of the prostate (STEAP) is considered attractive due to its overexpression in human prostate cancer tissues. Our study constitutes the first assessment of the in vivo effectiveness of STEAP-based vaccination in prophylactic and therapeutic mouse models. Two delivery systems, cDNA delivered by gene gun and Venezuelan equine encephalitis virus-like replicon particles (VRP), both encoding mouse STEAP (mSTEAP) and three vaccination strategies were used. Our results show that mSTEAP-based vaccination was able to induce a specific CD8 T-cell response against a newly defined mSTEAP epitope that prolonged the overall survival rate in tumor-challenged mice very significantly. This was achieved without any development of autoimmunity. Surprisingly, CD4 T cells that produced IFNgamma, tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) played the main role in tumor rejection in our model as shown by using CD4- and CD8-deficient mice. In addition, the presence of high IL 12 levels in the tumor environment was associated with a favorable antitumor response. Finally, the therapeutic effect of STEAP vaccination was also assessed and induced a modest but significant delay in growth of established, 31 day old tumors. Taken together, our data suggest that vaccination against mSTEAP is a viable option to delay tumor growth. PMID- 17283173 TI - Long-term treatment with tamoxifen facilitates translocation of estrogen receptor alpha out of the nucleus and enhances its interaction with EGFR in MCF-7 breast cancer cells. AB - The therapeutic benefit of tamoxifen in patients with hormone-dependent breast cancer is limited by acquired resistance to this drug. To investigate the biological alterations responsible for tamoxifen resistance, an in vitro model was established. After 6-month continuous exposure to tamoxifen (10(-7) mol/L), growth of MCF-7 breast cancer cells was no longer inhibited by this antiestrogen. Although there was no significant increase in the basal levels of activated mitogen-activated protein kinase (MAPK), tamoxifen-resistant (TAM-R) cells exhibited enhanced sensitivity to epidermal growth factor (EGF) and estradiol stimulated activation of MAPK. Tamoxifen elicited rapid phosphorylation of MAPK, in contrast to its antagonistic activity in control cells. Blockade of the EGF receptor (EGFR)/MAPK pathway caused more dramatic inhibition of growth of TAM-R cells than the control cells. An increased amount of estrogen receptor alpha (ERalpha) was coimmunoprecipitated with EGFR from TAM-R cells although the total levels of these receptors were not increased. Notably, ERalpha seemed to redistribute to extranuclear sites in TAM-R cells. Increased ERalpha immunoreactivity in the cytoplasm and plasma membrane of TAM-R cells was shown by fluorescent microscopy and by Western analysis of isolated cellular fractions. In TAM-R cells, an increased amount of c-Src was coprecipitated with EGFR or ERalpha. Blockade of c-Src activity resulted in redistribution of ERalpha back to the nucleus and in reduction of its interaction with EGFR. Prolonged blockade of c-Src activity restored sensitivity of TAM-R cells to tamoxifen. Our results suggest that enhanced nongenomic function of ERalpha via cooperation with the EGFR pathway is one of the mechanisms responsible for acquired tamoxifen resistance. PMID- 17283174 TI - Impaired dihydrotestosterone catabolism in human prostate cancer: critical role of AKR1C2 as a pre-receptor regulator of androgen receptor signaling. AB - We previously reported the selective loss of AKR1C2 and AKR1C1 in prostate cancers compared with their expression in paired benign tissues. We now report that dihydrotestosterone (DHT) levels are significantly greater in prostate cancer tumors compared with their paired benign tissues. Decreased catabolism seems to account for the increased DHT levels as expression of AKR1C2 and SRD5A2 was reduced in these tumors compared with their paired benign tissues. After 4 h of incubation with benign tissue samples, (3)H-DHT was predominantly catabolized to the 5alpha-androstane-3alpha,17beta-diol metabolite. Reduced capacity to metabolize DHT was observed in tumor samples from four of five freshly isolated pairs of tissue samples, which paralleled loss of AKR1C2 and AKR1C1 expression. LAPC-4 cells transiently transfected with AKR1C1 and AKR1C2, but not AKR1C3, were able to significantly inhibit a dose-dependent, DHT-stimulated proliferation, which was associated with a significant reduction in the concentration of DHT remaining in the media. R1881-stimulated proliferation was equivalent in all transfected cells, showing that metabolism of DHT was responsible for the inhibition of proliferation. PC-3 cells overexpressing AKR1C2 and, to a lesser extent, AKR1C1 were able to significantly inhibit DHT-dependent androgen receptor reporter activity, which was abrogated by increasing DHT levels. We speculate that selective loss of AKR1C2 in prostate cancer promotes clonal expansion of tumor cells by enhancement of androgen-dependent cellular proliferation by reducing DHT metabolism. PMID- 17283175 TI - DNA methylation of tumor suppressor genes in clinical remission predicts the relapse risk in acute myeloid leukemia. AB - Epigenetic changes play an important role in leukemia pathogenesis. DNA methylation is among the most common alterations in leukemia. The potential role of DNA methylation as a biomarker in leukemia is unknown. In addition, the lack of molecular markers precludes minimal residual disease (MRD) estimation for most patients with hematologic malignancies. We analyzed the potential of aberrant DNA promoter methylation as a biomarker for MRD in acute leukemias. Quantitative real time PCR methods with bisulfite-modified DNA were established to quantify MRD based on estrogen receptor alpha (ERalpha) and/or p15(INK4B) methylation. Methylation analyses were done in >370 DNA specimens from 180 acute leukemia patients and controls. Methylation of ERalpha and/or p15(INK4B) occurred frequently and specifically in acute leukemia but not in healthy controls or in nonmalignant hematologic diseases. Aberrant DNA methylation was detectable in >20% of leukemia patients during clinical remission. In pediatric acute lymphoblastic leukemia, methylation levels during clinical remission correlated closely with T-cell receptor/immunoglobulin MRD levels (r = +0.7, P < 0.01) and were associated with subsequent relapse. In acute myelogenous leukemia patients in clinical remission, increased methylation levels were associated with a high relapse risk and significantly reduced relapse-free survival (P = 0.003). Many patients with acute leukemia in clinical remission harbor increased levels of aberrant DNA methylation. Analysis of methylation MRD might be used as a novel biomarker for leukemia patients' relapse risk. PMID- 17283177 TI - Genetic variation in base excision repair genes and the prevalence of advanced colorectal adenoma. AB - Base excision repair (BER) corrects DNA damage caused by oxidative stress and low folate intake, which are putative risk factors for colorectal neoplasia. To examine the relationship between genetic variation in BER genes and colorectal adenoma risk, we conducted a case-control study of 767 cases of advanced colorectal adenoma and 773 controls from the baseline screening exam of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cases included participants diagnosed with advanced left-sided adenoma, and controls were subjects without evidence of a left-sided polyp by sigmoidoscopy, frequency matched to cases on race and gender. Twenty single nucleotide polymorphisms were genotyped in four BER genes (APEX1, PARP1, POLB, and XRCC1), and conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association with colorectal adenoma. Two variants with possible functional significance were associated with risk. The APEX1 51H variant was associated with a borderline significant decreased risk of colorectal adenoma (OR, 0.66; 95% CI, 0.44-1.00), and the XRCC1 399Q variant was inversely associated with risk among Caucasians (OR, 0.80; 95% CI, 0.64-0.99). Homozygotes at two PARP1 loci (A284A and IVS13+118G>A) were also associated with a decreased risk of colorectal adenoma compared with wild-type carriers (OR, 0.70; 95% CI, 0.49-0.98 for both), which was restricted to advanced adenomas displaying histologically aggressive characteristics (OR, 0.51; 95% CI, 0.33-0.78, P = 0.002 for PARP1 A284A). This study suggests that polymorphisms in APEX1, XRCC1, and PARP1 may be associated with advanced colorectal adenoma. PMID- 17283176 TI - Protein kinase C epsilon, which sensitizes skin to sun's UV radiation-induced cutaneous damage and development of squamous cell carcinomas, associates with Stat3. AB - Chronic exposure to UV radiation (UVR) is the major etiologic factor in the development of human skin cancers including squamous cell carcinoma (SCC). We have shown that protein kinase C(epsilon) (PKC(epsilon)), a Ca(2+)-independent, phospholipid-dependent serine/threonine kinase, is an endogenous photosensitizer. PKC(epsilon) is among the six isoforms (alpha, delta, epsilon, eta, mu, and zeta) expressed in both mouse and human skin. PKC(epsilon) transgenic mice, which overexpress PKC(epsilon) in the basal epidermal cells and cells of the hair follicle, are highly sensitive to UVR-induced cutaneous damage and development of SCC. We now present that PKC(epsilon)-overexpressing, but not PKC(delta) overexpressing, transgenic mice, when exposed to a single (4 kJ/m(2)) or repeated (four doses, 2 kJ/m(2)/dose, thrice weekly) UVR, emitted by Kodacel-filtered FS 40 sun lamps, elicit constitutive phosphorylation of signal transducers and activators of transcription 3 (Stat3) at both Tyr705 and Ser727 residues. UVR induced phosphorylation of Stat3 accompanied increased expression of Stat3 regulated genes (c-myc, cyclin D1, cdc25A, and COX-2). In reciprocal immunoprecipitation/blotting experiments, phosphorylated Stat3 co immunoprecipitated with PKC(epsilon). As observed in vivo using PKC(epsilon) knockout mice and in vitro in an immunocomplex kinase assay, PKC(epsilon) phosphorylated Stat3 at Ser727 residue. These results indicate for the first time that (a) PKC(epsilon) is a Stat3Ser727 kinase; (b) PKC(epsilon)-mediated phosphorylation of StatSer727 may be essential for transcriptional activity of Stat3; and (c) UVR-induced phosphorylation of Ser727 may be a key component of the mechanism by which PKC(epsilon) imparts sensitivity to UVR-induced development of SCC. PMID- 17283178 TI - Early childhood gender differences in anterior and posterior cerebral blood flow velocity and autoregulation. AB - OBJECTIVE: We aimed to describe gender differences in blood flow velocity and autoregulation of the anterior and posterior cerebral circulations in prepubertal children. METHODS: A prospective observational cohort study was performed at Harborview Medical Center's Cerebrovascular Laboratory after institutional review board approval, consent, and assent procedures. Children underwent measurement of middle cerebral and basilar artery flow velocities and cerebral autoregulation testing of the middle cerebral and basilar arteries. Cerebral autoregulation was quantified using the autoregulatory index, and estimated cerebrovascular resistance was calculated. Autoregulatory index <0.4 reflects impaired cerebral autoregulation. Data are presented as mean +/- SD. Patients were healthy 4- to 8 year-old children. RESULTS: Forty-eight children (24 boys and 24 girls) 4 to 8 years of age (mean: 6 +/- 2 years) were enrolled. Middle cerebral artery flow velocity was higher than basilar artery flow velocity (96 +/- 13 vs 65 +/- 11 cm/s). Girls had higher middle cerebral artery flow velocity (99 +/- 11 vs 91 +/- 13 cm/s) and basilar artery flow velocity (70 +/- 10 vs 61 +/- 9 cm/s) than boys. Cerebral autoregulation was intact in all children. There was no gender difference in autoregulation between the middle cerebral artery (boys: 0.97 +/- 0.07; girls: 0.94 +/- 0.11) or basilar artery (boys: 0.94 +/- 0.13; girls: 0.94 +/- 0.11). CONCLUSIONS: Similar to older children and adults, girls between 4 and 8 years of age had higher middle cerebral and basilar artery flow velocity than age-matched boys. This difference may reflect inherent differences in cerebral metabolic rate and/or estimated cerebrovascular resistance between the genders. PMID- 17283179 TI - Pediatric and emergency medicine residents' attitudes and practices for analgesia and sedation during lumbar puncture in pediatric patients. AB - OBJECTIVE: Analgesia and sedation for painful procedures in children are safe and effective, yet our experience is that pain management during lumbar puncture is suboptimal. We aim to document factors that influence residents' decisions to use analgesia and sedation during lumbar puncture and to compare pediatric and emergency medicine residents' practices. METHODS: A survey was developed and sent to pediatric and emergency medicine residents from across Canada that inquired about clinical practices, learning experiences, current use of analgesia and sedation for lumbar puncture, and their clinical reasoning for using or abstaining from using analgesia and sedation. The Student's t and chi2 tests were used to compare the 2 resident groups. RESULTS: Of the 374 residents to whom the survey was sent, 245 completed the survey. Pediatric residents reported performing lumbar punctures with no local anesthetic much more frequently. Pediatric residents used EMLA (AstraZeneca, Wilmington, DE) more frequently and injectable lidocaine less frequently. Pediatric residents used sedation for lumbar puncture at least once, more frequently than emergency medicine residents, and used mostly benzodiazepines. Both groups used ketamine at a similar rate. Pediatric residents reported that they witnessed adverse events of sedation more frequently. Although pediatric residents were responsible for teaching trainees the lumbar-puncture procedure significantly more frequently, they reported less educational opportunities during residency themselves and that they were less likely to recommend the use of local anesthetic during lumbar puncture when teaching the procedure. CONCLUSIONS: Several significant differences exist between the pediatric residents and emergency medicine residents we surveyed. Pediatric residents were using less injectable local anesthesia for lumbar puncture in children and more sedation for the procedure and have had notably less training in the use of sedation. Pediatric residents have more teaching responsibilities than their emergency medicine residents colleagues and are inconsistently recommending the use of local anesthetics for lumbar puncture. PMID- 17283180 TI - Toward creating family-friendly work environments in pediatrics: baseline data from pediatric department chairs and pediatric program directors. AB - OBJECTIVE: The objective was to determine baseline characteristics of pediatric residency training programs and academic departments in regard to family-friendly work environments as outlined in the Report of the Task Force on Women in Pediatrics. METHODS: We conducted Web-based anonymous surveys of 147 pediatric department chairs and 203 pediatric program directors. The chair's questionnaire asked about child care, lactation facilities, family leave policies, work-life balance, and tenure and promotion policies. The program director's questionnaire asked about family leave, parenting, work-life balance, and perceptions of "family-friendliness." RESULTS: The response rate was 52% for program directors and 51% for chairs. Nearly 60% of chairs reported some access to child care or provided assistance locating child care; however, in half of these departments, demand almost always exceeded supply. Lactation facilities were available to breastfeeding faculty in 74% of departments, although only 57% provided access to breast pumps. A total of 78% of chairs and 90% of program directors reported written maternity leave policies with slightly fewer reporting paternity leave policies. The majority (83%) of chairs reported availability of part-time employment, whereas only 27% of program directors offered part-time residency options. Most departments offered some flexibility in promotion and tenure. CONCLUSIONS: Although progress has been made, change still is needed in many areas in pediatric departments and training programs, including better accessibility to quality child care; improved lactation facilities for breastfeeding mothers; clear, written parental leave policies; and flexible work schedules to accommodate changing demands of family life. PMID- 17283181 TI - Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP p150Glued, ORP1L, and the receptor betalll spectrin. AB - The small GTPase Rab7 controls late endocytic transport by the minus end-directed motor protein complex dynein-dynactin, but how it does this is unclear. Rab7 interacting lysosomal protein (RILP) and oxysterol-binding protein-related protein 1L (ORP1L) are two effectors of Rab7. We show that GTP-bound Rab7 simultaneously binds RILP and ORP1L to form a RILP-Rab7-ORP1L complex. RILP interacts directly with the C-terminal 25-kD region of the dynactin projecting arm p150(Glued), which is required for dynein motor recruitment to late endocytic compartments (LEs). Still, p150(Glued) recruitment by Rab7-RILP does not suffice to induce dynein-driven minus-end transport of LEs. ORP1L, as well as betaIII spectrin, which is the general receptor for dynactin on vesicles, are essential for dynein motor activity. Our results illustrate that the assembly of microtubule motors on endosomes involves a cascade of linked events. First, Rab7 recruits two effectors, RILP and ORP1L, to form a tripartite complex. Next, RILP directly binds to the p150(Glued) dynactin subunit to recruit the dynein motor. Finally, the specific dynein motor receptor Rab7-RILP is transferred by ORP1L to betaIII spectrin. Dynein will initiate translocation of late endosomes to microtubule minus ends only after interacting with betaIII spectrin, which requires the activities of Rab7-RILP and ORP1L. PMID- 17283182 TI - Formation of microtubule-based traps controls the sorting and concentration of vesicles to restricted sites of regenerating neurons after axotomy. AB - Transformation of a transected axonal tip into a growth cone (GC) is a critical step in the cascade leading to neuronal regeneration. Critical to the regrowth is the supply and concentration of vesicles at restricted sites along the cut axon. The mechanisms underlying these processes are largely unknown. Using online confocal imaging of transected, cultured Aplysia californica neurons, we report that axotomy leads to reorientation of the microtubule (MT) polarities and formation of two distinct MT-based vesicle traps at the cut axonal end. Approximately 100 microm proximal to the cut end, a selective trap for anterogradely transported vesicles is formed, which is the plus end trap. Distally, a minus end trap is formed that exclusively captures retrogradely transported vesicles. The concentration of anterogradely transported vesicles in the former trap optimizes the formation of a GC after axotomy. PMID- 17283183 TI - Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa. AB - To identify the mechanisms of ultraviolet radiation (UVR)-induced cell death, for which the tumor suppressor p53 is essential, we have analyzed mouse embryonic fibroblasts (MEFs) and keratinocytes in mouse skin that have specific apoptotic pathways blocked genetically. Blocking the death receptor pathway provided no protection to MEFs, whereas UVR-induced apoptosis was potently inhibited by Bcl-2 overexpression, implicating the mitochondrial pathway. Indeed, Bcl-2 overexpression boosted cell survival more than p53 loss, revealing a p53 independent pathway controlled by the Bcl-2 family. Analysis of primary MEFs lacking individual members of its BH3-only subfamily identified major initiating roles for the p53 targets Noxa and Puma. In the transformed derivatives, where Puma, unexpectedly, was not induced by UVR, Noxa had the dominant role and Bim a minor role. Furthermore, loss of Noxa suppressed the formation of apoptotic keratinocytes in the skin of UV-irradiated mice. Collectively, these results demonstrate that UVR activates the Bcl-2-regulated apoptotic pathway predominantly through activation of Noxa and, depending on cellular context, Puma. PMID- 17283185 TI - Residual active granzyme B in cathepsin C-null lymphocytes is sufficient for perforin-dependent target cell apoptosis. AB - Cathepsin C activates serine proteases expressed in hematopoietic cells by cleaving an N-terminal dipeptide from the proenzyme upon granule packaging. The lymphocytes of cathepsin C-null mice are therefore proposed to totally lack granzyme B activity and perforin-dependent cytotoxicity. Surprisingly, we show, using live cell microscopy and other methodologies, that cells targeted by allogenic CD8(+) cytotoxic T lymphocyte (CTL) raised in cathepsin C-null mice die through perforin-dependent apoptosis indistinguishable from that induced by wild type CTL. The cathepsin C-null CTL expressed reduced but still appreciable granzyme B activity, but minimal granzyme A activity. Also, in contrast to mice with inactivation of both their granzyme A/B genes, cathepsin C deficiency did not confer susceptibility to ectromelia virus infection in vivo. Overall, our results indicate that although cathepsin C clearly generates the majority of granzyme B activity, some is still generated in its absence, pointing to alternative mechanisms for granzyme B processing and activation. Cathepsin C deficiency also results in considerably milder immune deficiency than perforin or granzyme A/B deficiency. PMID- 17283187 TI - Human and murine granzyme B exhibit divergent substrate preferences. AB - The cytotoxic lymphocyte protease granzyme B (GzmB) can promote apoptosis through direct processing and activation of members of the caspase family. GzmB can also cleave the BH3-only protein, BID, to promote caspase-independent mitochondrial permeabilization. Although human and mouse forms of GzmB exhibit extensive homology, these proteases diverge at residues predicted to influence substrate binding. We show that human and mouse GzmB exhibit radical differences in their ability to cleave BID, as well as several other key substrates, such as ICAD and caspase-8. Moreover, pharmacological inhibition of caspases clonogenically rescued human and mouse target cells from apoptosis initiated by mouse GzmB, but failed to do so in response to human GzmB. These data demonstrate that human and murine GzmB are distinct enzymes with different substrate preferences. Our observations also illustrate how subtle differences in enzyme structure can radically affect substrate selection. PMID- 17283189 TI - National survey on the susceptibility of Bacteroides fragilis group: report and analysis of trends in the United States from 1997 to 2004. AB - The susceptibility trends for the species of the Bacteroides fragilis group against various antibiotics from 1997 to 2004 were determined by using data for 5,225 isolates referred by 10 medical centers. The antibiotic test panel included ertapenem, imipenem, meropenem, ampicillin-sulbactam, piperacillin-tazobactam, cefoxitin, clindamycin, moxifloxacin, tigecycline, chloramphenicol, and metronidazole. From 1997 to 2004 there were decreases in the geometric mean (GM) MICs of imipenem, meropenem, piperacillin-tazobactam, and cefoxitin for many of the species within the group. B. distasonis showed the highest rates of resistance to most of the beta-lactams. B. fragilis, B. ovatus, and B. thetaiotaomicron showed significantly higher GM MICs and rates of resistance to clindamycin over time. The rate of resistance to moxifloxacin of B. vulgatus was very high (MIC range for the 8-year study period, 38% to 66%). B. fragilis, B. ovatus, and B. distasonis and other Bacteroides spp. exhibited significant increases in the rates of resistance to moxifloxacin over the 8 years. Resistance rates and GM MICs for tigecycline were low and stable during the 5-year period over which this agent was studied. All isolates were susceptible to chloramphenicol (MICs < 16 microg/ml). In 2002, one isolate resistant to metronidazole (MIC = 64 microg/ml) was noted. These data indicate changes in susceptibility over time; surprisingly, some antimicrobial agents are more active now than they were 5 years ago. PMID- 17283184 TI - Midbody and primary cilium of neural progenitors release extracellular membrane particles enriched in the stem cell marker prominin-1. AB - Expansion of the neocortex requires symmetric divisions of neuroepithelial cells, the primary progenitor cells of the developing mammalian central nervous system. Symmetrically dividing neuroepithelial cells are known to form a midbody at their apical (rather than lateral) surface. We show that apical midbodies of neuroepithelial cells concentrate prominin-1 (CD133), a somatic stem cell marker and defining constituent of a specific plasma membrane microdomain. Moreover, these apical midbodies are released, as a whole or in part, into the extracellular space, yielding the prominin-1-enriched membrane particles found in the neural tube fluid. The primary cilium of neuroepithelial cells also concentrates prominin-1 and appears to be a second source of the prominin-1 bearing extracellular membrane particles. Our data reveal novel origins of extracellular membrane traffic that enable neural stem and progenitor cells to avoid the asymmetric inheritance of the midbody observed for other cells and, by releasing a stem cell membrane microdomain, to potentially influence the balance of their proliferation versus differentiation. PMID- 17283186 TI - betaIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG. AB - High densities of ion channels at axon initial segments (AISs) and nodes of Ranvier are required for initiation, propagation, and modulation of action potentials in axons. The organization of these membrane domains depends on a specialized cytoskeleton consisting of two submembranous cytoskeletal and scaffolding proteins, ankyrinG (ankG) and betaIV spectrin. However, it is not known which of these proteins is the principal organizer, or if the mechanisms governing formation of the cytoskeleton at the AIS also apply to nodes. We identify a distinct protein domain in betaIV spectrin required for its localization to the AIS, and show that this domain mediates betaIV spectrin's interaction with ankG. Dominant-negative ankG disrupts betaIV spectrin localization, but does not alter endogenous ankG or Na(+) channel clustering at the AIS. Finally, using adenovirus for transgene delivery into myelinated neurons, we demonstrate that betaIV spectrin recruitment to nodes of Ranvier also depends on binding to ankG. PMID- 17283188 TI - In vitro and in vivo activities of synthetic trioxolanes against major human schistosome species. AB - Schistosomiasis is a parasitic disease that remains of considerable public health significance in tropical and subtropical environments. Since the mainstay of schistosomiasis control is chemotherapy with a single drug, praziquantel, drug resistance is a concern. Here, we present new data on the antischistosomal properties of representative synthetic 1,2,4-trioxolanes (OZs). Exposure of adult Schistosoma mansoni for 24 h to a medium containing 20 mug/ml OZ209 reduced worm motor activity, induced tegumental alterations, and killed worms within 72 h. While exposure of S. mansoni to OZ78 had no apparent effect, addition of hemin reduced worm motor activity and caused tegumental damage. Administration of single 200-mg/kg of body weight oral doses of OZ78, OZ209, and OZ288 to mice harboring a juvenile S. mansoni infection resulted in worm burden reductions of 82.0 to 95.4%. In the adult infection model in mice, single 400-mg/kg doses of these compounds resulted in a maximum total worm burden reduction of 52.2%. High worm burden reductions (71.7 to 86.5%) were observed after administration of single 200-mg/kg doses of OZ78 and OZ288 to hamsters infected with either juvenile or adult S. mansoni. A single 200-mg/kg dose of OZ78 to hamsters infected with adult Schistosoma japonicum resulted in total and female worm burden reductions of 94.2 to 100%. Our results, along with the low toxicity, metabolic stability, and good pharmacokinetic properties of the OZs, indicate the potential for the development of novel broad-spectrum antischistosomal OZ drug candidates. PMID- 17283190 TI - Antimicrobial activities of daptomycin, vancomycin, and oxacillin in human monocytes and of daptomycin in combination with gentamicin and/or rifampin in human monocytes and in broth against Staphylococcus aureus. AB - We investigated the antistaphylococcal activity of daptomycin, vancomycin, oxacillin, gentamicin, and rifampin in human monocyte-derived macrophages. Compared with vancomycin and oxacillin, daptomycin had the most rapid and greatest antibacterial activity, but that of oxacillin was most sustained. The combination of daptomycin, gentamicin, and rifampin was most effective intracellularly, while daptomycin plus gentamicin and the three-drug combination were most effective extracellularly, completely eliminating viable Staphylococcus aureus. PMID- 17283191 TI - Species-specific differences in the susceptibilities of biofilms formed by Candida bloodstream isolates to echinocandin antifungals. AB - The echinocandin susceptibilities of bloodstream Candida isolates growing in a biofilm was investigated. Within the therapeutic range of concentrations of each drug, caspofungin and micafungin were active against biofilms formed by Candida albicans or C. glabrata but not those formed by C. tropicalis or C. parapsilosis. PMID- 17283193 TI - Dissemination of sul3-containing elements linked to class 1 integrons with an unusual 3' conserved sequence region among Salmonella isolates. AB - A sul3 domain (IS440-sul3-orf1-IS26) was found linked to an unusual 3' conserved sequence region (qacH) of class 1 integrons and detected among nontyphoid Salmonella isolates (n=47) from different sources. Three types of integrons differing in the gene cassette array (dfrA12-orfF-aadA2-cmlA1-aadA1, dfrA12-orfF aadA2/1, and estX-psp-aadA2-cmlA1-aadA1) were found associated with this sul3 domain. They were associated with particular clones and specific high-molecular weight plasmids. PMID- 17283192 TI - Miltefosine (hexadecylphosphocholine) inhibits cytochrome c oxidase in Leishmania donovani promastigotes. AB - Miltefosine (hexadecylphosphocholine [HePC]) is currently on trial as a first choice, orally active drug for the treatment of visceral leishmaniasis when resistance to organic pentavalent antimonials becomes epidemic. However, data on the targets involved in its leishmanicidal mechanism have, until now, been only fragmentary. We have carried out a systematic study of the alterations induced on the bioenergetic metabolism of Leishmania donovani promastigotes by HePC. Overnight incubation with HePC caused a significant decline in the intracellular ATP levels of the parasites, together with a reduction in the oxygen consumption rate and mitochondrial depolarization, while the integrity of the plasma membrane remained undamaged. In a further step, the effects of HePC on the respiratory chain were addressed in digitonized parasites. The inhibition of the oxygen consumption rate caused by HePC was not reverted either with the uncoupling agent carbonyl cyanide p-trifluoromethoxyphenylhydrazone or with tetramethyl-p phenylenediamine plus ascorbate, which feeds the electron transport chain at the level of cytochrome c. These results suggest that cytochrome c oxidase is a likely target in the complex leishmanicidal mechanism of HePC. This was further confirmed from the finding that this enzyme was specifically inhibited in a dose dependent manner by HePC, but not the cytochrome c reductase, ruling out an unspecific effect of HePC on the respiratory chain. PMID- 17283194 TI - Fitness cost of staphylococcal cassette chromosome mec in methicillin-resistant Staphylococcus aureus by way of continuous culture. AB - We examined the effect of introducing type I or IV staphylococcal cassette chromosome mec (SCCmec) elements on the growth yield of Staphylococcus aureus in glucose-limited continuous culture. Type I showed increased glucose consumption and ATP demand per gram of cells synthesized and decreased cell yield compared to those of the parent strain. In contrast, type IV SCCmec elements had no adverse energetic effect. PMID- 17283196 TI - Fluoroquinolone resistance in Haemophilus influenzae is associated with hypermutability. AB - Forty-three percent (12/28) of ciprofloxacin (CIP)-nonsusceptible respiratory isolates of Haemophilus influenzae were hypermutable, compared with 8.5% (3/35) in the CIP-susceptible control group (P=0.002). CIP-nonsusceptible mutants were obtained with hypermutable strains only; these mutants developed three resistance mechanisms in a step-by-step process: target modifications, loss of a porin protein, and increased efflux. PMID- 17283195 TI - Compartmental pharmacokinetic analysis of oral amprenavir with secondary peaks. AB - Amprenavir is a protease inhibitor that has been shown to have secondary peaks postulated to be due to enterohepatic recycling. We propose a model to describe the pharmacokinetics of amprenavir which accommodates the secondary peak(s). A total of 82 healthy human immunodeficiency virus (HIV)-seronegative subjects were administered a single 600-mg dose of amprenavir as part of adult AIDS Clinical Trials Group protocol A5043. Serial blood samples were obtained over 24 h. Samples were analyzed for amprenavir and fit to a compartmental model using ADAPT II software, with all relevant parameters conditional with respect to bioavailability. The model accommodated secondary peaks by incorporating clearance out of the central compartment with delayed instantaneous release back into the gut compartment. The data were weighted by the inverse of the estimated measurement error variance; model discrimination was determined using Akaike's Information Criteria. A total of 76 subjects were evaluable in the study analysis. The data were best fit by a two-compartment model, with 98.7% of the subjects demonstrating a secondary peak. Amprenavir had a mean total clearance of 1.163 liters/h/kg of body weight (0.7), a central volume of distribution of 1.208 liters/kg (0.8), a peripheral volume of distribution of 8.2 liters/kg (0.81), and distributional clearance of 0.04 liters/h/kg (0.81). The time to the secondary peak was 7.86 h (0.17), and clearance into a recycling compartment was 0.111 liters/kg/h (0.74). Amprenavir pharmacokinetics has been well described using a two-compartment model with clearance to a recycling compartment and release back into the gut. The nature of the secondary peaks may be an important consideration for the interpretation of amprenavir plasma concentrations during therapeutic drug monitoring. PMID- 17283197 TI - Bactericidal activities of meropenem and ertapenem against extended-spectrum-beta lactamase-producing Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh model. AB - The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-beta-lactamase (ESBL)-producing isolates with a wide range of MICs. Human-simulated dosing regimens in mice were designed to approximate the free drug percent time above the MIC (fT>MIC) observed for humans following meropenem at 1 g every 8 h and ertapenem at 1 g every 24 h. An in vivo neutropenic mouse thigh infection model was used to examine the bactericidal effects against 31 clinical ESBL Escherichia coli and Klebsiella pneumoniae isolates and 2 non-ESBL isolates included for comparison at a standard 10(5) inoculum. Three isolates were examined at a high 10(7) inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (microg/ml) of 0.125 (0.03 to 32), than did ertapenem, with 0.5 (0.012 to 128). Seven of the 31 ESBL isolates were removed from the efficacy analysis due to their inability to establish infection in the mouse model. When MICs wereMIC>or=23%) and meropenem (fT>MIC>or=75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of>or=2 microg/ml (fT>MICMIC=30 to 65%). At a 10(7) inoculum, both agents eradicated bacteria due to adequate exposures (fT>MIC=20 to 45%). Due to low MICs, no difference in bacterial kill was noted for the majority of ESBL isolates tested. However, for isolates with raised ertapenem MICs of>or=2 microg/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC. PMID- 17283198 TI - Molecular epidemiology of CTX-M-producing Escherichia coli in the Calgary Health Region: emergence of CTX-M-15-producing isolates. AB - A study was designed to describe the molecular epidemiology of CTX-M-producing Escherichia coli over a 6-year period (2000 to 2005) in a large well-defined Canadian region with a centralized laboratory system. Molecular characterization was done by isoelectric focusing, PCR, and automated sequencing, while genetic relatedness was determined by pulsed-field gel electrophoresis with XbaI. Of the 552 viable extended-spectrum beta-lactamase-producing E. coli isolates isolated, 354 (64%) were positive for blaCTX-M genes associated with ISEcp1; 211 produced CTX-M-14, 128 produced CTX-M-15, 5 produced CTX-M-2, 4 produced CTX-M-3, 4 produced CTX-M-24, and 2 produced CTX-M-27. CTX-M-positive isolates were significantly more resistant to the fluoroquinolones than CTX-M-negative isolates, while CTX-M-15 producers were more likely to be resistant to gentamicin and tobramycin. There was a predominance of CTX-M-14 during the first 4 years of the study period, with community outbreaks associated with cluster 14A during 2000, 2001, and 2003. A substantial increase in CTX-M-15 producers occurred during the last 18 months and was due to clusters 15A and 15AR (where AR indicates related to A) in the hospital and nursing home sectors. Our results demonstrate that the persistence and dissemination of CTX-M genes among E. coli populations in larger geographic health care regions is dynamic, with the continuous emergence of clonally related CTX-M-15. This study illustrates the importance of molecular surveillance in tracking CTX-M-producing E. coli strains in the community and investigating their influx into hospitals. PMID- 17283200 TI - In vitro inhibition of Plasmodium falciparum rosette formation by Curdlan sulfate. AB - Spontaneous binding of infected erythrocytes to uninfected erythrocytes to form rosettes is a property of some strains of Plasmodium falciparum that is linked to severe complications of malaria. Curdlan sulfate (CRDS) is a sulfated glycoconjugate compound that is chemically similar to known rosette-inhibiting drugs such as heparin. CRDS has previously been shown to have antimalarial activity in vitro and is safe for clinical use. Here we show that CRDS at therapeutic levels (10 to 100 microg/ml) significantly reduces rosette formation in vitro in seven P. falciparum laboratory strains and in a group of 18 African clinical isolates. The strong ability to inhibit rosetting suggests that CRDS has the potential to reduce the severe complications and mortality rates from P. falciparum malaria among African children. Our data support further clinical trials of CRDS. PMID- 17283199 TI - Common origin and fixation of Plasmodium falciparum dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance in a low-transmission area in South America. AB - Recent studies indicated that sensitive parasites could increase in frequency in a population when drugs are removed, suggesting that the life span of affordable antimalarial drugs could be expanded. We studied 97 samples from Bolivar State, Venezuela, an area where sulfadoxine-pyrimethamine (SP) has not been used for 8 years due to its ineffectiveness. We characterized point mutations in two genes that have been implicated in resistance to SP, dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps). We also assayed neutral microsatellite markers around the dhfr (chromosome 4) and dhps (chromosome 8) genes and on chromosomes 2 and 3 to track the origin and spread of resistant alleles. We found that drug resistant SP mutants are fixed in the population. Two genotypes were present in the samples, dhfr(50R/51I/108N) dhps(437G/540E/581G) (90.7%) and dhfr(51I/108N) dhps(437G/581G) (9.3%). We show a single microsatellite haplotype for all of the dhfr and dhps alleles, and the alleles at the microsatellite loci are different from those present in Africa. Thus, in these samples from Venezuela, there is a single origin for both dhfr and dhps SP-resistant alleles, and these alleles originated independently of those characterized from Africa. Furthermore, this is the first report of a "hitchhiking effect" on the genetic variation around dhps due to selection by SP using an extensive set of microsatellite markers. Our results indicate that, in areas where there is limited gene flow, the fixation of drug-resistant parasites in the population is stable, even after drug selection is relaxed. PMID- 17283201 TI - Molecular epidemiology of macrolide and tetracycline resistances in commensal Gemella sp. isolates. AB - The epidemiologic relatedness of 29 erythromycin-resistant Gemella sp. strains from normal flora, characterized previously, were evaluated by pulsed-field gel electrophoresis (PFGE). Three isolates carried the tet(O) gene and the tet(M) gene. The msr(A) gene was found in two Gemella morbillorum strains in combination with the erm(B) or mef(E) gene. The sequences of the mef(A/E), erm(B), and msr(A) genes showed a high similarity to the corresponding sequences of other gram positive cocci. All the strains harboring the mef(A/E) gene and the msr(D) gene possessed open reading frame 3 (ORF3)/ORF6. The 16 G. morbillorum isolates represented 15 distinct DNA profiles. Four clusters were identified (>or=80% genetic relatedness). The 12 Gemella haemolysans strains belonged to different PFGE types. The clonal diversity found suggests that horizontal transfer may be the main route through which erythromycin resistance is acquired. PMID- 17283202 TI - Human neural systems for conceptual knowledge of proper object use: a functional magnetic resonance imaging study. AB - Ideational apraxia is characterized by impaired knowledge of action concepts and proper object usage. The present functional magnetic resonance imaging study aimed at investigating the neural system underlying conceptual knowledge for proper object use in healthy subjects, when the effects of visuospatial properties and perceptual modality were taken into account. Subjects performed semantic decision tasks requiring retrieval of knowledge about either object functional purposes (functional task) or visuospatial object properties (visuospatial task) and perceptual control tasks. The semantic tasks were performed with pairs of either written object names or object drawings. Activation for the functional task in common for words and pictures, compared with the visuospatial and control tasks, was found in left parietal-temporal occipital (PTO) junction, inferior frontal, anterior dorsal premotor, and presupplementary motor areas. Ventral inferior frontal cortex activation correlated negatively with reaction time in the functional condition. No specific activation characterized the visuospatial task compared with the functional task. The conceptual tasks, compared with the control tasks, demonstrated overlapping activation in left PTO junction, prefrontal, dorsal premotor, cuneus, and inferior temporal areas. These results outline the neural processes underlying conceptual knowledge for proper object use. The left ventral inferior frontal gyrus might facilitate behavioral decisions regarding functional/pragmatical object properties. PMID- 17283204 TI - When does the brain inform the eyes whether and where to move? An EEG study in humans. AB - The current study addressed when in the course of stimulus processing, and in what brain areas, activity occurs that supports the interpretation of cues that signal the appropriateness of different and competing behaviors. Twelve subjects completed interleaved no-go-, pro-, and antitrials, whereas 64-channel electroencephalography was recorded. Principle component and distributed source analyses were used to evaluate the spatial distribution and time course of cortical activity supporting cue evaluation and response selection. By 158 ms poststimulus, visual cortex activity was lower for no-go trials than it was for both pro- and antitrials, consistent with an early sensory filter on the no-go cue. Prefrontal cortex (PFC) activity at 158 ms was highest during antitrials, consistent with this brain region's putative involvement in executive control. At 204 ms poststimulus, however, PFC activity was the same for pro- and antitrials, consistent with an ostensible role in response selection. PFC activity at 204 ms also was robustly inversely correlated (r = -0.75) with visual cortex activity on antitrials, perhaps indicating top-down modulation of early sensory processing that would decrease the probability of an error response. These data highlight how a distributed neural architecture supports the evaluation of stimuli and response choices. PMID- 17283203 TI - Distinct and convergent visual processing of high and low spatial frequency information in faces. AB - We tested for differential brain response to distinct spatial frequency (SF) components in faces. During a functional magnetic resonance imaging experiment, participants were presented with "hybrid" faces containing superimposed low and high SF information from different identities. We used a repetition paradigm where faces at either SF range were independently repeated or changed across consecutive trials. In addition, we manipulated which SF band was attended. Our results suggest that repetition and attention affected partly overlapping occipitotemporal regions but did not interact. Changes of high SF faces increased responses of the right inferior occipital gyrus (IOG) and left inferior temporal gyrus (ITG), with the latter response being also modulated additively by attention. In contrast, the bilateral middle occipital gyrus (MOG) responded to repetition and attention manipulations of low SF. A common effect of high and low SF repetition was observed in the right fusiform gyrus (FFG). Follow-up connectivity analyses suggested direct influence of the MOG (low SF), IOG, and ITG (high SF) on the FFG responses. Our results reveal that different regions within occipitotemporal cortex extract distinct visual cues at different SF ranges in faces and that the outputs from these separate processes project forward to the right FFG, where the different visual cues may converge. PMID- 17283205 TI - Activation of the D prostanoid 1 receptor suppresses asthma by modulation of lung dendritic cell function and induction of regulatory T cells. AB - Prostaglandins (PGs) can enhance or suppress inflammation by acting on different receptors expressed by hematopoietic and nonhematopoietic cells. Prostaglandin D(2) binds to the D prostanoid (DP)1 and DP2 receptor and is seen as a critical mediator of asthma causing vasodilation, bronchoconstriction, and inflammatory cell influx. Here we show that inhalation of a selective DP1 agonist suppresses the cardinal features of asthma by targeting the function of lung dendritic cells (DCs). In mice treated with DP1 agonist or receiving DP1 agonist-treated DCs, there was an increase in Foxp3(+) CD4(+) regulatory T cells that suppressed inflammation in an interleukin 10-dependent way. These effects of DP1 agonist on DCs were mediated by cyclic AMP-dependent protein kinase A. We furthermore show that activation of DP1 by an endogenous ligand inhibits airway inflammation as chimeric mice with selective hematopoietic loss of DP1 had strongly enhanced airway inflammation and antigen-pulsed DCs lacking DP1 were better at inducing airway T helper 2 responses in the lung. Triggering DP1 on DCs is an important mechanism to induce regulatory T cells and to control the extent of airway inflammation. This pathway could be exploited to design novel treatments for asthma. PMID- 17283206 TI - A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin. AB - The molecular basis for Toll-like receptor (TLR) recognition of microbial ligands is unknown. We demonstrate that mouse and human TLR5 discriminate between different flagellins, and we use this difference to map the flagellin recognition site on TLR5 to 228 amino acids of the extracellular domain. Through molecular modeling of the TLR5 ectodomain, we identify two conserved surface-exposed regions. Mutagenesis studies demonstrate that naturally occurring amino acid variation in TLR5 residue 268 is responsible for human and mouse discrimination between flagellin molecules. Mutations within one conserved surface identify residues D295 and D367 as important for flagellin recognition. These studies localize flagellin recognition to a conserved surface on the modeled TLR5 structure, providing detailed analysis of the interaction of a TLR with its ligand. These findings suggest that ligand binding at the beta sheets results in TLR activation and provide a new framework for understanding TLR-agonist interactions. PMID- 17283207 TI - CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. AB - Nonhealing forms of leishmaniasis in humans are commonly associated with elevated levels of the deactivating cytokine IL-10, and in the mouse, normally chronic infections can be cleared in the absence of IL-10. Using a Leishmania major strain that produces nonhealing dermal lesions in a T helper type 1 (Th1) cell polarized setting, we have analyzed the cellular sources of IL-10 and their relative contribution to immune suppression. IL-10 was produced by innate cells, as well as CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(-) T cells in the chronic lesion. Nonetheless, only IL-10 production by antigen-specific CD4(+)CD25( )Foxp3(-) T cells, the majority of which also produced IFN-gamma, was necessary for suppression of acquired immunity in Rag(-/-) reconstituted mice. Surprisingly, Rag(-/-) mice reconstituted with naive CD4(+) T cells depleted of natural T regulatory cells developed more severe infections, associated with elevated levels of IL-10 and, especially, Th2 cytokines in the site. The data demonstrate that IL-10-producing Th1 cells, activated early in a strong inflammatory setting as a mechanism of feedback control, are the principal mediators of T cell-derived IL-10-dependent immune suppression in a chronic intracellular infection. PMID- 17283208 TI - Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. AB - Embryonic stem cells have the distinct potential for tissue regeneration, including cardiac repair. Their propensity for multilineage differentiation carries, however, the liability of neoplastic growth, impeding therapeutic application. Here, the tumorigenic threat associated with embryonic stem cell transplantation was suppressed by cardiac-restricted transgenic expression of the reprogramming cytokine TNF-alpha, enhancing the cardiogenic competence of recipient heart. The in vivo aptitude of TNF-alpha to promote cardiac differentiation was recapitulated in embryoid bodies in vitro. The procardiogenic action required an intact endoderm and was mediated by secreted cardio-inductive signals. Resolved TNF-alpha-induced endoderm-derived factors, combined in a cocktail, secured guided differentiation of embryonic stem cells in monolayers produce cardiac progenitors termed cardiopoietic cells. Characterized by a down regulation of oncogenic markers, up-regulation, and nuclear translocation of cardiac transcription factors, this predetermined population yielded functional cardiomyocyte progeny. Recruited cardiopoietic cells delivered in infarcted hearts generated cardiomyocytes that proliferated into scar tissue, integrating with host myocardium for tumor-free repair. Thus, cardiopoietic programming establishes a strategy to hone stem cell pluripotency, offering a tumor-resistant approach for regeneration. PMID- 17283211 TI - G-ribo: a new structural motif in ribosomal RNA. AB - Analysis of the available crystal structures of the ribosome and of its subunits has revealed a new RNA motif that we call G-ribo. The motif consists of two double helices positioned side-by-side and connected by an unpaired region. The juxtaposition of the two helices is kept by a complex system of tertiary interactions spread over several layers of stacked nucleotides. In the center of this arrangement, the ribose of a nucleotide from one helix is specifically packed with the ribose and the minor-groove edge of a guanosine from the other helix. In total, we found eight G-ribo motifs in both ribosomal subunits. The location of these motifs suggests that at least some of them play an important role in the formation of the ribosome structure and/or in its function. PMID- 17283210 TI - A novel family of C. elegans snRNPs contains proteins associated with trans splicing. AB - In many Caenorhabditis elegans pre-mRNAs, the RNA sequence between the 5' cap and the first 3' splice site is replaced by trans-splicing a short spliced leader (SL) from the Sm snRNP, SL1. C. elegans also utilizes a similar Sm snRNP, SL2, to trans-splice at sites between genes in polycistronic pre-mRNAs from operons. How do SL1 and SL2 snRNPs function in different contexts? Here we show that the SL1 snRNP contains a complex of SL75p and SL21p, which are homologs of novel proteins previously reported in the Ascaris SL snRNP. Interestingly, we show that the SL2 snRNP does not contain these proteins. However, SL75p and SL26p, a paralog of SL21p, are components of another Sm snRNP that contains a novel snRNA species, Sm Y. Knockdown of SL75p is lethal. However, knockdown of either SL21p or SL26p alone leads to cold-sensitive sterility, whereas knockdown of both SL21p and SL26p is lethal. This suggests that these two proteins have overlapping functions even though they are associated with different classes of snRNP. These phenotypic relationships, along with the association of SL26p with SL75p, imply that, like the SL1 RNA/Sm/SL75p/SL21p complex, the Sm Y/Sm/SL75p/SL26p complex is associated with trans-splicing. PMID- 17283209 TI - Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. AB - Although interferon gamma (IFN-gamma) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine known to counteract IFN-gamma effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-gamma-secreting T bet(+)Foxp3(-) T helper type 1 (Th1) cells were found to be the major producers of IL-10 in these animals. Further analysis revealed that the same IL-10(+)IFN gamma(gamma) population displayed potent effector function against the parasite while, paradoxically, also inducing profound suppression of IL-12 production by antigen-presenting cells. Although at any given time point only a fraction of the cells appeared to simultaneously produce IL-10 and IFN-gamma, IL-10 production could be stimulated in IL-10(-)IFN-gamma(+) cells by further activation in vitro. In addition, experiments with T. gondii-specific IL-10(+)IFN-gamma(+) CD4 clones revealed that although IFN-gamma expression is imprinted and triggered with similar kinetics regardless of the state of Th1 cell activation, IL-10 secretion is induced more rapidly from recently activated than from resting cells. These findings indicate that IL-10 production by CD4(+) T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens. PMID- 17283212 TI - Trans-acting glmS catalytic riboswitch: locked and loaded. AB - A recently discovered class of gene regulatory RNAs, coined riboswitches, are commonly found in noncoding segments of bacterial and some eukaryotic mRNAs. Gene up- or down-regulation is triggered by binding of a small organic metabolite, which typically induces an RNA conformational change. Unique among these noncoding RNAs is the glmS catalytic riboswitch, or ribozyme, found in the 5' untranslated region of the glmS gene in Gram-positive bacteria. It is activated by glucosamine-6-phosphate (GlcN6P), leading to site-specific backbone cleavage of the mRNA and subsequent repression of the glmS gene, responsible for cellular GlcN6P production. Recent biochemical and structural evidence suggests that the GlcN6P ligand acts as a coenzyme and participates in the cleavage reaction without inducing a conformational change. To better understand the role of GlcN6P in solution structural dynamics and function, we have separated the glmS riboswitch core from Bacillus subtilis into a trans-cleaving ribozyme and an externally cleaved substrate. We find that trans cleavage is rapidly activated by nearly 5000-fold to a rate of 4.4 min(-1) upon addition of 10 mM GlcN6P, comparable to the cis-acting ribozyme. Fluorescence resonance energy transfer suggests that this ribozyme-substrate complex does not undergo a global conformational change upon ligand binding in solution. In addition, footprinting at nucleotide resolution using terbium(III) and RNase V1 indicates no significant changes in secondary and tertiary structure upon ligand binding. These findings suggest that the glmS ribozyme is fully folded in solution prior to binding its activating ligand, supporting recent observations in the crystalline state. PMID- 17283213 TI - Combining SELEX and the yeast three-hybrid system for in vivo selection and classification of RNA aptamers. AB - Aptamers are small nucleic acid ligands that bind to their targets with specificity and high affinity. They are generated by a combinatorial technology, known as SELEX. This in vitro approach uses iterative cycles of enrichment and amplification to select binders from nucleic acid libraries of high complexity. Here we combine SELEX with the yeast three-hybrid system in order to select for RNA aptamers with in vivo binding activity. As a target molecule, we chose the RNA recognition motif-containing RNA-binding protein Rrm4 from the corn pathogen Ustilago maydis. Rrm4 is an ELAV-like protein containing three N-terminal RNA recognition motifs (RRMs). It has been implicated in microtubule-dependent RNA transport during pathogenic development. After 11 SELEX cycles, four aptamer classes were identified. These sequences were further screened for their in vivo binding activity applying the yeast three-hybrid system. Of the initial aptamer classes only members of two classes were capable of binding in vivo. Testing representatives of both classes against Rrm4 variants mutated in one of the three RRM domains revealed that these aptamers interacted with the third RRM. Thus, the yeast three-hybrid system is a useful extension to the SELEX protocol for the identification and characterization of aptamers with in vivo binding activity. PMID- 17283214 TI - Elevated FMR1 mRNA in premutation carriers is due to increased transcription. AB - Carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene have levels of FMR1 mRNA that are elevated by as much as 10-fold in peripheral blood leukocytes and CNS tissue. The excess expanded repeat mRNA, per se, is now believed to result in forms of clinical involvement that are largely restricted to premutation carriers, including the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). Although evidence to date suggests that the elevated mRNA is not due to increased stability, the basis for the increase is not known. In the current study, we have determined the relative transcriptional activities of premutation and normal FMR1 alleles using a highly sensitive nuclear run-on assay that involves immunocapture of digoxigenin-modified run-on transcripts followed by PCR amplification of the nascent transcripts. Using the nuclear run-on approach, we demonstrate that the rate of run-on synthesis of FMR1 transcripts is increased in premutation alleles. The current run-on assay should be broadly applicable to studies of other genes with promoters of weak to moderate strength. The fraction of capped FMR1 mRNA remains unaltered for premutation transcripts, indicating that elevated message levels are not due to premature escape from the cotranscriptional capping process. We also show that, in contrast to the situation with myotonic dystrophy, there is no net nuclear sequestration of premutation FMR1 mRNA. Finally, we have demonstrated that AGG interruptions within the CGG repeat element do not influence FMR1 mRNA levels. PMID- 17283216 TI - GPs' strategies in intercultural clinical encounters. AB - BACKGROUND: In North America and Europe, patients and physicians are increasingly likely to come from non-Western cultural backgrounds. The expectations of these patients may not match those of physicians. OBJECTIVE: To identify strategies used by GPs with patients from cultures other than their own. METHODS: We conducted a qualitative inductive study based on 25 semi-structured interviews with family physicians practising in Montreal, Canada. We elicited physicians' strategies when dealing with patients from a cultural background different from their own. We began by asking physicians to describe an encounter they found difficult and one they found easy. RESULTS: Physicians reported three types of strategies: (i) insistence on patient adaptation to local beliefs and behaviours; (ii) physician adaptation to what he or she assumed patients wanted; and (iii) negotiation of a mutually acceptable plan. Individual physicians did not adopt the same strategy in all situations. Their choice of strategy depended on the topic. When dealing with issues they felt deeply about, such as the autonomy of women, many physicians insisted on patient adaptation. Physicians used a patient centred model of care, but had no framework to elicit information about patients' culture. CONCLUSIONS: A patient-centred model of care enables physicians to consult effectively despite a wide range of cultural differences between themselves and their patients. However, their lack of a conceptual framework for addressing cultural difference prevents systematic data collection and consideration of challenges to respect for individual autonomy. Physician training should include the provision of an explicit conceptual framework for approaching patients from a different culture. PMID- 17283217 TI - UK GPs' and practice nurses' views of continuity of care for patients with type 2 diabetes. AB - BACKGROUND: Continuity of care is widely regarded as a core value of primary care. Type 2 diabetes is a common chronic disease with major health, social and economic impacts. Primary health care professionals in many countries are involved in the management of patients with type 2 diabetes, but their perspectives on continuity remain neglected in research. OBJECTIVE: To explore UK GPs' and nurses' experiences of continuity of care for patients with type 2 diabetes in primary care settings. METHODS: Semi-structured individual interviews were conducted with 16 GPs and 18 practice nurses who manage patients with type 2 diabetes recruited from 20 practices with various organizational structures in Leeds, UK. RESULTS: Three types of continuities were identified: relational continuity from the same health care professional, team continuity from a group of health care professionals and cross-boundary continuity across primary secondary care settings. Relational continuity was influenced by the quality of the patient-health care professional relationship, policy of the National Health Service (NHS) in the UK (new General Medical Services contract), walk-in centres, the behaviour of receptionists and the structure and systems of the practice. Team and cross-boundary continuities were influenced by the relationship between team members and by effective communication. Relational continuity contributed to more 'personal care', but the usual health care professional might know less about diabetes. Team continuity was important in providing 'physical care', but patients could be confused by conflicting advice from different professionals. Cross-boundary continuity helps to provide 'expert advice', but is dependent upon effective communication. CONCLUSION: GPs and practice nurses dealing with patients with type 2 diabetes identified three types of continuities, each influenced by several factors. Relational continuity deals better with psychosocial care while team continuity promotes better physical care; therefore, imposing one type of continuity may inhibit good diabetic care. Cross-boundary continuity between primary and secondary care is fundamental to contemporary diabetic services and ways should be found to achieve more effective communication. PMID- 17283215 TI - New bioinformatic tools for analysis of nucleotide modifications in eukaryotic rRNA. AB - This report presents a valuable new bioinformatics package for research on rRNA nucleotide modifications in the ribosome, especially those created by small nucleolar RNA:protein complexes (snoRNPs). The interactive service, which is not available elsewhere, enables a user to visualize the positions of pseudouridines, 2'-O-methylations, and base methylations in three-dimensional space in the ribosome and also in linear and secondary structure formats of ribosomal RNA. Our tools provide additional perspective on where the modifications occur relative to functional regions within the rRNA and relative to other nearby modifications. This package of new tools is presented as a major enhancement of an existing but significantly upgraded yeast snoRNA database available publicly at http://people.biochem.umass.edu/sfournier/fournierlab/snornadb/. The other key features of the enhanced database include details of the base pairing of snoRNAs with target RNAs, genomic organization of the yeast snoRNA genes, and information on corresponding snoRNAs and modifications in other model organisms. PMID- 17283218 TI - Non-cardiac chest pain: a retrospective cohort study of patients who attended a Rapid Access Chest Pain Clinic. AB - BACKGROUND: Rapid Access Chest Pain Clinics have recently been introduced to assist in the management of primary care patients experiencing suspected cardiac chest pain. OBJECTIVE: To study the longer term outcome for patients referred to a Rapid Access Chest Pain Clinic and then given a non-cardiac diagnosis. METHODS: The study collected retrospective data from a cohort of all patients attending the Rapid Access Chest Pain Clinic based in the cardiorespiratory Department at the York District Hospital, England. Questionnaires were sent to all patients who attended the Rapid Access Chest Pain Clinic during the previous 14 months and were diagnosed with non-cardiac chest pain. Participants reported on their chest pain, subsequent episodes of primary and secondary care and their beliefs about causation of pain. RESULTS: Of the patients referred to the Rapid Access Chest Pain Clinic, 235 (52%) did not have cardiac chest pain. Of these patients, 161 (69%) returned the questionnaire, nearly half of whom reported ongoing chest pain. The mean time since Clinic attendance was approximately 8 months and the median duration of ongoing chest pain was 5.4 months. Women were twice as likely as men to continue to be experiencing pain but did not report more frequent or severe pain on average. More than 50% of the non-cardiac group were not convinced by their negative cardiac diagnosis. CONCLUSION: There is an ongoing challenge to support patients with non-cardiac chest pain, including the provision of reassurance that their pain is very unlikely to be caused by their heart. PMID- 17283219 TI - Thalidomide induces limb deformities by perturbing the Bmp/Dkk1/Wnt signaling pathway. AB - Thalidomide, a sedative originally used to treat morning sickness and now used to treat leprosy and multiple myeloma, is also a teratogen that induces birth defects in humans such as limb truncations and microphthalmia. However, the teratogenic mechanism of action of this drug remains obscure. Thalidomide induces limb and eye defects in the chicken embryo at an EC50 of 50 microg/kg egg wt and apoptosis in primary human embryonic fibroblasts (HEFs) at an EC50 of 8.9 microM. Using these model systems, we demonstrate by semiquantitative reverse transcriptase-polymerase chain reaction and whole-mount in situ hybridization that thalidomide-induced oxidative stress enhances signaling through bone morphogenetic proteins (Bmps). This leads to up-regulation of the Bmp target gene and Wnt antagonist Dickkopf1 (Dkk1) with subsequent inhibition of canonical Wnt/beta-catenin signaling and increased cell death as shown by trypan blue and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. Thalidomide-induced cell death was dramatically reduced in HEFs and in embryonic limb buds by the use of inhibitors against Bmps, Dkk1, and Gsk3beta, a beta catenin antagonist acting downstream of Dkk1 in the Wnt pathway. Most interestingly, blocking of Dkk1 or Gsk3beta dramatically counteracts thalidomide induced limb truncations and microphthalmia. From this, we conclude that perturbing of Bmp/Dkk1/Wnt signaling is central to the teratogenic effects of thalidomide. PMID- 17283220 TI - A novel approach to ultrasensitive diagnosis using supramolecular protein nanoparticles. AB - We report on the ultrasensitive protein nanoprobe system that specifically captures disease marker (autoantibodies of Type I diabetes in this case) with attomolar sensitivity. The system relies on supramolecular protein nanoparticles that bind a specific antibody [65 kDa glutamate decarboxylase (GAD65)-specific autoantibody, i.e., the early marker of Type I diabetes]. The ultrasensitive detection of early marker of Type I diabetes during the early phase of pancreatic beta-cell destruction is important because individuals at high risk of developing Type I diabetes can be identified several years before the clinical onset of the ailment. The bacterial expression of chimera genes encoding N-[human ferritin heavy chain (hFTN-H)]::[specific antigenic epitope]-C produces supramolecular nanoparticles with uniform diameters (10-15 nm), owing to self-assembly activity of hFTN-H. Each nanoparticle, formed by intermolecular self-assembly between the chimera protein molecules, is subjected to carrying a large number (presumably, 24) of epitopes with a homogeneous and stable conformation per autoantibody binding, thereby allowing substantial enhancement of sensitivity. The sensitivity was finally boosted to 3 attomolar concentration of the autoantibodies, 4-9 orders of magnitude more sensitive than conventional immunoassays. Also, this ultrasensitive protein nanoprobe successfully detected natural autoantibodies in the sera from Type I diabetic patients. The attomolar sensitivity was successfully reproduced on the detection of other antibodies, i.e., monoclonal antibodies against hepatitis B surface antigen. With the two antibody markers above, the feasibility of simultaneous and multiplexing-mode detection was also demonstrated. PMID- 17283221 TI - The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K ATPase. AB - FXYD1 is a transmembrane protein predominantly expressed in excitable tissues that associates with and regulates Na/K ATPase. PKA phosphorylates FXYD1 at serine 68 (S68), however, the effects of phosphorylation on Na/K ATPase activity are not fully characterized. The objectives of this study were to characterize Na/K ATPase currents in FXYD1 wild-type (WT) and knockout (KO) adult mouse ventricular myocytes, and investigate the effects of FXYD1 on Na/K ATPase currents using the whole-cell patch-clamp technique. A peptide representing the 19 C-terminal residues of FXYD1 (FXYD1(54-72)) was introduced into the interior of FXYD1 KO and WT myocytes through the patch pipette. K-sensitive Na/K ATPase currents were higher in KO myocytes (2.9+/-0.1 pA/pF; n=4) compared with WT (1.9+/-0.1 pA/pF; n=4). Unphosphorylated FXYD1(54-72), at a concentration of 4 microM, reduced the currents in WT (from 2.1+/-0.1 to 1.3+/-0.1 pA/pF; P<0.05, n=7) and KO (from 2.9+/-0.1 to 1.7+/-0.1 pA/pF; P<0.05, n=5), whereas, 1 microM of FXYD1(54-72) phosphorylated at S68 increased currents in WT (from 1.91+/-0.09 to 3.1+/-0.5 pA/pF; P<0.05, n=6) and KO (from 2.7+/-0.11 to 3.8+/-0.2 pA/pF; P<0.05, n=6) myocytes. Coimmunoprecipitation studies demonstrated that S68 phosphorylated and unphosphorylated FXYD1(54-72) associates with Na/K ATPase alpha1 subunit. We conclude that unphosphorylated FXYD1 inhibits Na/K ATPase, whereas S68 phosphorylated FXYD1 stimulates Na/K ATPase to a level above that seen in the absence of FXYD1. PMID- 17283222 TI - The hepatocyte nuclear factor 6 (HNF6) and FOXA2 are key regulators in colorectal liver metastases. AB - The molecular causes leading to secondary liver malignancies are unknown. Here we report regulation of major hepatic nuclear factors in human colorectal liver metastases and primary colonic cancer. Notably, the genes coding for HNF6, HNF1beta, and C/EBPgamma were selectively regulated in liver metastases. We therefore studied protein expression of regulated transcription factors and found unacetylated HNF6 to be a hallmark of colorectal liver metastases. For its known interaction with HNF6, we investigated expression of FOXA2, which we found to be specifically induced in colorectal liver metastases. By electromobility shift assay, we examined DNA binding of disease regulated transcription factors. Essentially, no HNF6 DNA binding was observed. We also searched for sequence variations in the DNA binding domains of HNF6, but did not identify any mutation. Furthermore, we probed for expression of 28 genes targeted by HNF6. Mostly transcript expression was repressed except for tumor growth. In conclusion, we show HNF6 protein expression to be driven by the hepatic environment. Its expression is not observed in healthy colon or primary colonic cancer. HNF6 DNA binding is selectively abrogated through lack of post-translational modification and interaction with FOXA2. Targeting of FOXA2 and HNF6 may therefore enable mechanism-based therapy for colorectal liver metastases. PMID- 17283223 TI - Interleukin-4 induces human hepatocyte apoptosis through a Fas-independent pathway. AB - IL-4 is overexpressed in liver grafts during severe recurrent hepatitis C and rejection. Hepatocyte apoptosis is involved in both these phenomena. We therefore examined the proapoptotic effect of IL-4 on HepG2 cells and human hepatocytes in vitro, together with the underlying mechanisms. We first measured IL-4 receptor expression, STAT6 activation by IL-4, and STAT6 inhibition by an anti-IL-4 antibody or by STAT6 siRNA transfection. We then focused on the pathways involved in IL-4-mediated apoptosis and the role of STAT6 activation in apoptosis initiation. The IL-4 receptor was expressed on both cell types, and STAT6 was activated by IL-4. Both anti-IL-4 and STAT-6 siRNA inhibited this activation. IL 4 induced apoptosis of both HepG2 cells (P=0.008 vs. untreated control) and human hepatocytes (P<0.001 vs. untreated control). IL-4 reduced the mitochondrial membrane potential, activated Bid and Bax, and augmented caspase 3, 8, and 9 activity. STAT6 blockade inhibited IL-4-induced apoptosis. Expression of Fas and Fas ligand was unaffected when HepG2 cells and hepatocytes were cultured with IL 4, and Fas/FasL pathway blockade failed to inhibit IL-4-induced apoptosis. These results show that IL-4 induces apoptosis of human hepatocytes through IL-4 receptor binding, STAT6 activation, decreased mitochondrial membrane potential, and increased caspase activation, independently of the Fas pathway. IL-4 might thus contribute to the progression of severe liver graft damage. PMID- 17283224 TI - Role of nitric oxide in alpha-melanocyte-stimulating hormone-induced hypotension in the nucleus tractus solitarii of the spontaneously hypertensive rats. AB - Pro-opiomelanocortin (POMC) is expressed in the nucleus tractus solitarii (NTS) of the brainstem, where nitric oxide (NO) plays an important role in cardiovascular regulation. The POMC-derived neuropeptides and their receptors are important regulators of energy homeostasis and cardiovascular functions in the central nervous system. In this study, we investigated the cardiovascular effect of alpha-melanocyte-stimulating hormone (alpha-MSH), a POMC-derived neuropeptide, and its relationship with NO pathway in the NTS of spontaneously hypertensive rats (SHR). Unilateral microinjection of alpha-MSH (0.3-300 pmol) into the NTS resulted in a dose-dependent hypotension and bradycardia in urethane-anesthetized SHR. The alpha-MSH-induced hypotension was abolished by pretreatment with the antagonist of melanocortin-3/4 receptor (MC-3/4R), Ac-Nle-c[Asp-His-D-Nal(2')-Arg Trp-Lys]-NH2 (SHU9119). Blockade of cAMP/protein kinase A (PKA), the downstream effector of melanocortin receptors, by previous injection of N-[2-(4 bromocinnamylamino)ethyl]-5-isoquinoline (H89) also ablated the cardiovascular effect of alpha-MSH. To elucidate the role of NO pathway in alpha-MSH-evoked hypotension, pretreatment with Nomega-nitro-L-arginine methyl ester, a universal inhibitor of nitric-oxide synthase (NOS), partially reversed the depressor and bradycardic effects of alpha-MSH. Furthermore, previous application of the inducible NOS (iNOS) inhibitor, aminoguanidine, but not the neuronal NOS inhibitor, 7-nitroindazole, attenuated the cardiovascular effect of alpha-MSH. Histological analysis revealed the colocalization of MC-4R, but not MC-3R, with iNOS in the NTS of SHR. In summary, intra-NTS injection of alpha-MSH induces hypotension and bradycardia of SHR via MC-4R signaling, which activates cAMP/PKA and iNOS. PMID- 17283225 TI - Pharmacokinetic-pharmacodynamic modeling of the respiratory depressant effect of norbuprenorphine in rats. AB - The objective of this investigation was to characterize the pharmacokinetic pharmacodynamic (PK-PD) correlation of buprenorphine's active metabolite norbuprenorphine for the effect on respiration in rats. Following i.v. administration in rats (dose range 0.32-1.848 mg), the time course of the concentration in plasma was determined in conjunction with the effect in ventilation as determined with a novel whole-body plethysmography technique. The PK of norbuprenorphine was best described by a three-compartment PK model with nonlinear elimination. A saturable biophase distribution model with a power PD model described the PK-PD relationship best. No saturation of the effect at high concentrations was observed, indicating that norbuprenorphine acts as a full agonist with regard to respiratory depression. Moreover, analysis of the hysteresis based on the combined receptor association-dissociation biophase distribution model yielded high values of the rate constants for receptor association and dissociation, indicating that these processes are not rate limiting. In a separate analysis, the time course of the plasma concentrations of buprenorphine and norbuprenorphine following administration of both the parent drug and the metabolite were simultaneously analyzed based on a six-compartment PK model with nonlinear elimination of norbuprenorphine. This analysis showed that following i.v. administration, 10% of the administered dose of buprenorphine is converted into norbuprenorphine. By simulation it is shown that following i.v. administration of buprenorphine, the concentrations of norbuprenorphine reach values that are well below the values causing an effect on respiration. PMID- 17283226 TI - Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro. AB - Thyroid hormone (T(3)) is a key regulator of fetal organ maturation. Premature elevations of thyroid hormone may lead to a 'mature' cardio-phenotype. Thyroid hormone will stimulate maturation of ovine fetal cardiomyocytes in culture by decreasing their proliferative capacity. Group 1 fetal cardiomyocytes (approximately 135 days gestation) were incubated with T3 (1.5, 3, 10, and 100 nM) and bromodeoxyuridine (BrdU; 10 microM) for 24 and 48 h. Group 2 cardiomyocytes were cultured with T3 alone for later protein analysis of cell cycle regulators. At all concentrations, T3 decreased BrdU uptake fourfold in serum media (P<0.001 versus serum, n=5). Following serum-free (SF) T3 treatment, BrdU uptake was inhibited when compared with serum (P<0.001 versus serum, n=5). p21 expression increased threefold (P<0.05 versus serum free, n=4) and cyclin D1 expression decreased twofold (P<0.05 versus serum, n=4) in T3-treated cardiomyocytes. (1) T3 inhibits fetal cardiomyocyte proliferation, while (2) p21 protein levels increase, and (3) cyclin D1 levels decrease. Thus, T3 may be a potent regulator of cardiomyocyte proliferation and maturation in the late gestation fetus. PMID- 17283227 TI - Regulation of body mass and adiposity in the field vole, Microtus agrestis: a model of leptin resistance. AB - Adult mammals are typically highly resistant to perturbations in their energy balance. In obese humans, however, this control appears to be lost. Apart from a few exceptional cases, this loss of control occurs despite appropriate levels of circulating leptin -- suggesting that elevated adiposity may be a consequence of failure to respond to the leptin signal: leptin resistance. When cold-acclimated male field voles (Microtus agrestis) are transferred from short (SD, 8 h light) to long (LD, 16 h light) photoperiods, they increase dramatically in body mass and fatness for about 4 weeks. After this period, their mass stabilizes at a new plateau about 25% higher than animals maintained in SD. The increase in adiposity is not caused by significant increases in food intake, but reflects an increase in digestive efficiency. Measures of circulating leptin reveal that the increased adiposity is matched by increased circulating leptin. By infusing voles with exogenous leptin, we have demonstrated that SD voles are leptin sensitive (reducing both body mass and food intake), whereas LD animals are leptin resistant. Voles may therefore be a useful model for understanding the process of leptin resistance. The change in leptin sensitivity in voles was not associated with changes in the levels of gene expression of the orexogenic or anorexogenic neuropeptides, such as neuropeptide Y, agouti-related peptide, POMC and cocaine- and amphetamine-regulated transcript, measured in the hypothalamic arcuate nucleus (ARC). During the phase that body mass was increasing, however, there was a transient increase in the ARC expression of suppressor of cytokine signalling-3 (SOCS3). These data suggest that the changes in the expression of SOCS3 in the ARC may be involved in leptin resistance. However, the mechanism by which these changes may be linked to alterations in digestive efficiency that underpin the changes in adiposity, or how the differences are signalled by changes in photoperiod, remains unclear. PMID- 17283228 TI - Characterisation of 11beta-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat. AB - Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11beta hydroxysteroid dehydrogenase type 1 (11beta-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying the metabolic syndrome mediating adipocyte hyperplasia and hypertrophy in the omental (OM) depot. Orbital adipose tissue (OF) is the site of intense inflammation and tissue remodelling in several orbital inflammatory disease states. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with subcutaneous (SC) and OM depots. Using an automated histological characterisation technique, OF adipocytes were found to be significantly smaller (parameters: area, maximum diameter and perimeter) than OM and SC adipocytes (P<0 x 001). Although immunohistochemical analyses demonstrated resident CD68+ cells in all three whole tissue adipose depots, OF CD68 mRNA and protein expression exceeded that of OM and SC (mRNA, P<0 x 05; protein, P<0 x 001). In addition, there was higher expression of glucocorticoid receptor (GR)alpha mRNA in the OF whole tissue depot (P<0 x 05). Conversely, 11beta-HSD1 mRNA together with the markers of late adipocyte differentiation (FABP4 and G3PDH) were significantly lower in OF. Primary cultures of OF preadipocytes demonstrated predominant 11beta HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta HSD1 but abundant GRalpha compared with SC and OM. OF harbours a large CD68+ population. These characteristics define an orbital microenvironment that has the potential to respond to sight-threatening orbital inflammatory disease. PMID- 17283229 TI - Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization. AB - Adiponectin and, especially, its oligomeric complex composition have been suggested to be critical in determining insulin sensitivity. Pro-inflammatory cytokines play an important role in the development of insulin resistance in obesity and associated diseases. Therefore, we investigated the effect of long term exposure of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL 1beta, and interferon (IFN)-gamma on total insulin-sensitizing adiponectin secretion and adiponectin complex formation from human adipocytes. In parallel, adipocyte delipidation and leptin production levels were monitored. The present study demonstrates that TNF-alpha, IL-1beta, and IFN-gamma dose and time dependently suppressed total adiponectin secretion within 7 days (60, 70, and 35% reduction respectively). IL-6 was also able to reduce (50%) adiponectin production, although only in combination with exogenous soluble IL-6 receptors (sIL-6R). However, the oligomeric distribution (high, middle, and low molecular weight (HMW) complexes) of secreted adiponectin was not altered by any of these cytokines. All studied pro-inflammatory cytokines resulted in delipidation and reduction of lipid-laden adipocyte numbers. Despite this reduction of lipid-laden adipocytes, TNF-alpha, IL-6/sIL-6R, and IL-1beta stimulated leptin release. Our data indicate that (i) long-term pro-inflammatory cytokine exposure downregulates total adiponectin secretion from delipidizing adipocytes and (ii) pro inflammatory cytokines are not important regulators of adipocyte-derived adiponectin oligomerization. Hence, their individual contribution to low expression of HMW adiponectin found in insulin-resistant conditions seems unlikely. Furthermore, delipidizing adipocytes and preadipocytes are active leptin producers when stimulated by TNF-alpha, IL-6/sIL-6R, and IL-1beta. PMID- 17283230 TI - Effects of maternal undernutrition during lactation on aromatase, estrogen, and androgen receptors expression in rat testis at weaning. AB - The goal of this study was to evaluate the effects of maternal malnutrition during lactation on serum levels of testosterone and estradiol, testicular testosterone concentration, aromatase, testicular androgen (AR) and estrogen alpha (ERalpha) receptors expression in the pups at weaning. From parturition until weaning, Wistar rats were separated into three groups: (C) control group, with free access to a standard laboratory diet containing 23% protein; protein energy restricted (PER) group, with free access to an isoenergy and protein restricted diet containing 8% protein; and energy-restricted (ER) group, receiving standard laboratory diet in restricted quantities, which were calculated according to the mean ingestion of the PER group. All pups were killed at weaning, corresponding to 21 days post partum. Compared with the C group, body weights (C=48 +/- 2.3 g; PER=20 +/- 1.3 g; ER=25.4 +/- 0.9 g; P<0.01) and testicular weights (C=0.15 +/- 0.02 g, PER=0.05 +/- 0.01 g, ER=0.06 +/- 0.02 g, P < 0.001) of both PER and ER groups were lower. However, there was no significant difference in the testicular/body weight ratio in PER and ER groups compared with the C group. The testosterone serum concentration (ng/ml) was significantly higher in the PER group compared with ER and C groups (C=0.09 +/- 0.012; PER=0.45 +/- 0.04; ER=0.15 +/- 0.03, P < 0.01). Testicular testosterone concentration (C=2.1 +/- 0.43; PER=6.5 +/- 0.7; ER=13 +/- 2.3, P < 0.01) was increased in treated groups when compared with controls. The estradiol serum concentration (pg/ml) was lower in both dietary groups (C=74 +/- 4.6; PER=49 +/- 3.2; ER=60 +/- 5.5, P < 0.01). The amounts of aromatase mRNA and ERalpha transcripts were significantly lower (P<0.05) in PER and ER groups; conversely AR (both mRNA and protein) was significantly enhanced (P<0.05) in treated animals. The nutritional state in early phases of development is important since we have demonstrated here that the maternal malnutrition during lactation leads to alterations in estradiol and testosterone serum concentrations, testicular testosterone concentration, AR and ERalpha expression together with a decrease of aromatase expression. All together, these changes of steroid status may be deleterious for future germ cell development and reproductive function of these male pups submitted to early malnutrition. PMID- 17283231 TI - Characterisation of proghrelin peptides in mammalian tissue and plasma. AB - Ghrelin is a 28 amino acid stomach peptide, derived from proghrelin(1-94), that stimulates GH release, appetite and adipose deposition. Recently, a peptide derived from proghrelin(53-75) -- also known as obestatin -- has been reported to be a physiological antagonist of ghrelin in the rat. Using four specific RIAs, we provide the first characterisation of proghrelin(1-94) peptides in human plasma, their modulation by metabolic manipulation and their distribution in mammalian tissues. ghrelin(1-28) immunoreactivity (IR) in human plasma and rat plasma/stomach consisted of major des-octanoyl and minor octanoylated forms, as determined by HPLC/RIA. Human plasma ghrelin(1-28) IR was significantly suppressed by food intake, oral glucose and 1 mg s.c. glucagon administration. ghrelin(1-28) IR and proghrelin(29-94) IR peptide distributions in the rat indicated that the stomach and gastrointestinal tract contain the highest amounts of the peptides. Human and rat plasma and rat stomach extracts contained a major IR peak of proghrelin(29-94)-like peptide as determined by HPLC/RIA, whereas no obestatin IR was observed. Human plasma proghrelin(29-94)-like IR positively correlated with ghrelin(1-28) IR, was significantly suppressed by food intake and oral glucose and shared with ghrelin(1-28) IR a negative correlation with body mass index. We found no evidence for the existence of obestatin as a unique, endogenous peptide. Rather, our data suggest that circulating and stored peptides derived from the carboxyl terminal of proghrelin (C-ghrelin) are consistent in length with proghrelin(29-94) and respond to metabolic manipulation, at least in man, in similar fashion to ghrelin(1-28). PMID- 17283233 TI - Prolactin inhibition in dams during lactation programs for overweight and leptin resistance in adult offspring. AB - Maternal malnutrition during lactation reduces prolactin (PRL) and milk production, alters milk composition, and programs the body weight of the offspring. Our study aimed to evaluate the long-term effects of maternal hypoprolactinemia at the end of lactation on food ingestion, body weight, amount of retroperitoneal white adipose tissue (RPWAT), leptinemia, and anorectic leptin effect in the adult offspring. Lactating rats were treated with bromocriptine (BRO), a PRL inhibitor, 1 mg twice a day, or saline (C - control) for the last 3 days of lactation. The body weight and food intake were monitored, and after sacrifice at 180 days, the RPWAT was weighted. In a second experiment, the anorectic leptin effect was tested on 180-day-old animals. Adult offspring whose mothers were BRO-treated showed higher body weight (10%), higher amount of RPWAT (2 x 3 times), higher total body fat (+39%), and hyperleptinemia (2 x 9 times) when compared with C, although food intake did not alter. After injection of leptin, the food ingestion at 2, 4 and 6 h was unaffected in BRO animals, confirming a resistance to the anorectic effect of leptin. Since the maternal PRL inhibition during lactation programs, a higher body weight with no alteration of food ingestion, we suggest a hypometabolic state. The leptin anorectic resistance can be due to the hyperleptinemia. We suggest that PRL changes during lactation can regulate body weight during adulthood. PMID- 17283232 TI - Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells. AB - Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions, including gonadal functions in humans and mammals. In the present study, we examined the direct effects of PCB on rat Leydig cells in vitro. Adult Leydig cells were purified by Percoll gradient centrifugation method and the purity of Leydig cells was also determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining method. Purified Leydig cells were exposed to different concentrations (10(- 10)-10(- 7) M) of PCB (Aroclor 1254) for 24 h under basal and LH-stimulated conditions. After the experimental period, cultured media were collected and used for the assay of testosterone and estradiol. The treated cells were used for the quantification of cell-surface LH receptors and activities of steroidogenic enzymes, such as cytochrome P(450) side-chain cleavage enzyme (P450scc), 3beta-HSD, and 17beta hydroxysteroid dehydrogenase (17beta-HSD). Leydig cellular enzymatic antioxidants, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, gamma-glutamyl transpeptidase, glutathione-S-transferase, and nonenzymatic antioxidants, such as vitamins C and E, were assayed. Lipid peroxidation (LPO) and reactive oxygen species (ROS) were also estimated in Leydig cells. In addition, total RNA was isolated from control and Aroclor 1254 exposed Leydig cells to monitor the steady-state mRNA levels by reverse transcription(RT)-PCR for steroidogenic acute-regulatory (StAR) protein, cytochrome P450scc, 3beta-HSD, and 17beta-HSD. Our results indicated that Aroclor 1254 (10(- 9), 10(- 8), and 10(- 7) M) treatments significantly inhibit basal and LH-stimulated testosterone and estradiol production. In addition, the activities of steroidogenic enzymes, enzymatic and nonenzymatic antioxidants were significantly diminished in a dose-dependent manner. However, LPO and ROS were elevated in a dose-dependent manner under basal and LH-stimulated conditions. RT PCR analysis of StAR mRNA level showed a decrease only in 10(- 7) M dose of Aroclor 1254 treatment, while cytochrome P(450)scc, 3beta-HSD, and 17beta-HSD mRNAs were drastically decreased in both 10(- 8) and 10(- 7) M Aroclor 1254 treatment. These findings suggest that PCBs can act directly on Leydig cells to diminish testosterone production by inhibiting gene expression of steroidogenic enzymes and antioxidant system. PMID- 17283234 TI - Gastric ghrelin cell development is hampered and plasma ghrelin is reduced by delayed weaning in rats. AB - The duration of breastfeeding has attracted much interest, as a prolonged period of breastfeeding has been shown to reduce the risk of developing obesity. The mechanism behind the reduced risk is, however, poorly understood. The novel hormone ghrelin augments appetite, promotes body weight increase and increases adiposity. The majority of circulating ghrelin emanates from endocrine cells in the oxyntic mucosa of the stomach. In newborn humans and rodents, the number of ghrelin cells is low after birth until weaning, when the cell population is greatly expanded. To date, information about the influence of weaning perturbations on ghrelin cell development is scarce. Therefore, we studied the effect of delayed weaning on gastric ghrelin expression and plasma ghrelin concentration. To this end, special food separator cages were used to prevent the pups from eating solid food, forcing them to drink milk up to 21 days of age. Gastric ghrelin expression was examined by immunocytochemistry and in situ hybridisation, and plasma concentrations were assessed by RIA. Our data showed that gastric ghrelin expression and plasma ghrelin concentration are maintained at a lower level by delayed weaning. We also found that the relation between gastric ghrelin expression and body weight was altered by delayed weaning. Thus, control rats displayed a positive correlation between ghrelin expression and body weight, while no such correlation was evident in animals with delayed weaning. We conclude that delayed weaning exerts a negative influence on ghrelin expression, and that the onset of solid food intake may trigger normal ghrelin expression. Therefore, we suggest that ghrelin may constitute a hormonal link between the duration of breastfeeding and body weight development. PMID- 17283235 TI - Induction of pulsatile secretion of leptin in horses following thyroidectomy. AB - Endocrine characteristics of Quarter Horse-type mares were determined during a 68 h feed deprivation and again in the same mares following surgical thyroidectomy (THX). A crossover experimental design was implemented, in which mares received brome hay available ad libitum (FED) or were food deprived (RES) for 68 h. Blood samples were collected every 20 min for 48 h, beginning 20 h after the onset of food deprivation. Concentrations of triiodothyronine and thyroxine were undetectable post-THX. Plasma concentrations of thyrotropin were greater post-THX versus pre-THX (P<0 x 001). Plasma concentrations of leptin were greater in the THX FED group than in the THX RES group (P<0 x 01). The existence of leptin pulse secretion was found only in post-THX compared with the same horses pre-THX (P=0 x 02). We theorize that non-pulsatile secretion of leptin may have contributed to the survival of this species, as it evolved in the regions of seasonal availability of food. Lack of pulsatile secretion of leptin may contribute to the accumulation of energy stores by modulating leptin sensitivity. PMID- 17283237 TI - Dual-acting peptide with prolonged glucagon-like peptide-1 receptor agonist and glucagon receptor antagonist activity for the treatment of type 2 diabetes. AB - Type 2 diabetes is characterized by reduced insulin secretion from the pancreas and overproduction of glucose by the liver. Glucagon-like peptide-1 (GLP-1) promotes glucose-dependent insulin secretion from the pancreas, while glucagon promotes glucose output from the liver. Taking advantage of the homology between GLP-1 and glucagon, a GLP-1/glucagon hybrid peptide, dual-acting peptide for diabetes (DAPD), was identified with combined GLP-1 receptor agonist and glucagon receptor antagonist activity. To overcome its short plasma half-life DAPD was PEGylated, resulting in dramatically prolonged activity in vivo. PEGylated DAPD (PEG-DAPD) increases insulin and decreases glucose in a glucose tolerance test, evidence of GLP-1 receptor agonism. It also reduces blood glucose following a glucagon challenge and elevates fasting glucagon levels in mice, evidence of glucagon receptor antagonism. The PEG-DAPD effects on glucose tolerance are also observed in the presence of the GLP-1 antagonist peptide, exendin(9-39). An antidiabetic effect of PEG-DAPD is observed in db/db mice. Furthermore, PEGylation of DAPD eliminates the inhibition of gastrointestinal motility observed with GLP-1 and its analogues. Thus, PEG-DAPD has the potential to be developed as a novel dual-acting peptide to treat type 2 diabetes, with prolonged in vivo activity, and without the GI side-effects. PMID- 17283236 TI - Mutual regulation of vasopressin- and oxytocin-induced glucagon secretion in V1b vasopressin receptor knockout mice. AB - [Arg8]-vasopressin (AVP) and oxytocin (OT) are neurohypophysial hormones which exert various actions, including the control of blood glucose, in some peripheral tissues. To investigate the type of receptors involved in AVP- and OT-induced glucagon secretion, we investigated the effect of these peptides on glucagon secretion in islets of wild-type (V1bR+/+) and vasopressin V1b receptor knockout (V1bR-/-) mice. AVP-induced glucagon secretion was significantly inhibited by the selective V1b receptor antagonist, SSR149415 (30%), and OT-induced glucagon secretion by the specific OT receptor antagonist, d(CH2)5[Tyr(Me)2, Thr4, Tyr NH(2)(9)]OVT (CL-14-26) (45%), in islets of V1bR+/+mice. AVP- and OT-induced glucagon secretions were not by the antagonist of each, but co-incubation with both 10(-6) M SSR149415 and 10(-6) M CL-14-26 further inhibited AVP- and OT induced glucagon secretions in islets of V1bR+/+ mice (57 and 69% of the stimulation values respectively). In addition, both AVP and OT stimulated glucagon secretion with the same efficacy in V1bR-/- mice as in V1bR+/+ mice. AVP and OT-induced glucagon secretion in V1bR-/- mice was significantly inhibited by CL-14-26. These results demonstrate that V1b receptors can mediate OT-induced glucagon secretion and OT receptors can mediate AVP-induced glucagon secretion in islets from V1bR+/+mice in the presence of a heterologous antagonist, while AVP and OT can stimulate glucagon secretion through the OT receptors in V1bR-/-mice, suggesting that the other receptor can compensate when one receptor is absent. PMID- 17283238 TI - Altered proinsulin conversion in rat pancreatic islets exposed long-term to various glucose concentrations or interleukin-1beta. AB - In order to elucidate a possible relationship between beta-cell function and conversion of proinsulin to insulin, isolated rat pancreatic islets were maintained in tissue culture for 1 week at various glucose concentrations (5 x 6 56 mM). Studies were also conducted on islets cultured for 48 h with interleukin 1beta (IL-1beta). By pulse-chase labelling and immunoprecipitation, the relative contents of newly synthesized proinsulin and insulin were determined. ELISA was used to analyse insulin and proinsulin content in medium and within islets. Using real-time PCR, the mRNA levels of proinsulin converting enzymes (PC1 and PC2) were studied. Islets cultured at 56 mM glucose had an increased proportion of newly synthesized proinsulin when compared with islets cultured at 5 x 6 mM glucose after a 90-min chase periods, however, no difference was observed after culture at 11 and 28 mM glucose. ELISA measurements revealed that culture at increased glucose concentrations as well as islet exposure to IL-1beta increased proinsulin accumulation in the culture media. The mRNA expression of PC1 was increased after culture at 11 and 28 mM glucose. Treatment for 48 h with IL-1beta increased the proportion of proinsulin both at 45 and 90 min when compared with control islets. These islets also displayed a decreased mRNA level of PC1 as well as PC2. Calculations of the half-time for proinsulin demonstrated a significant prolongation after treatment with IL-1beta. We conclude that a sustained functional stimulation by glucose of islets is coupled to a decreased conversion of proinsulin which is also true for islets treated with IL-1beta. This may contribute to the elevated levels of proinsulin found both at the onset of type 1 diabetes as well as in type 2 diabetes. PMID- 17283239 TI - The possible mechanisms by which phanoside stimulates insulin secretion from rat islets. AB - We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto Kakizaki (GK) rats were batch incubated or perifused. At both 3 x 3 and 16 x 7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 microM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3 x 3 mM glucose with 150 muM phanoside and 0 x 25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 microM phanoside alone. At 16 x 7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0 x 25 mM diazoxide (P<0 x 01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3 x 3 mM glucose but did not further increase the release at 16 x 7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3 x 3 mM glucose but decreased at 16 x 7 mM glucose (P<0 x 01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge protein did not affect insulin response to 150 microM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells. PMID- 17283240 TI - Changes in thrombospondin-1 levels in the endothelial cells of the anterior pituitary during estrogen-induced prolactin-secreting pituitary tumors. AB - Thrombospondin-1 (TSP-1), a multifunctional matrix glyco-protein, has been shown to control tumor growth by inhibiting angiogenesis in various tissues. However, the role of this glycoprotein in pituitary angiogenesis is not well studied. In this report, we determined the changes in the production and action of TSP-1 on endothelial cells in anterior pituitary following estradiol treatment, which is known to increase prolactin-secreting tumor growth and vascularization in this tissue. We showed that TSP-1 immunoreactive protein is distributed in the anterior pituitary, particularly in the endothelial cells. Estradiol treatment for 2 and 4 weeks decreased the total tissue immunoreactive level of TSP-1 as well as the endothelial cell-specific immunoreactive level of this protein in the anterior pituitary. The steroid treatment also decreased the protein levels of TSP-1 in anterior pituitary tissues and in purified pituitary endothelial cells in primary cultures. Determination of the effects of TSP-1 on proliferation and migration of pituitary-derived endothelial cells in primary cultures elucidated an inhibitory action of TSP-1 on these vascular cell functions. These results suggest that locally produced TSP-1 may regulate estrogen angiogenic action on the pituitary. PMID- 17283241 TI - Interplay of PI3K and cAMP/PKA signaling, and rapamycin-hypersensitivity in TGFbeta1 enhancement of FSH-stimulated steroidogenesis in rat ovarian granulosa cells. AB - Transforming growth factor (TGF) beta1 facilitates FSH-induced differentiation of rat ovarian granulosa cells. The signaling crosstalk between follicle stimulating hormone (FSH) and TGFbeta receptors remains unclear. This study was to investigate the interplay of cAMP/protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) signaling including mammalian target of rapamycin (mTOR)C1 dependence in FSH- and TGFbeta1-stimulated steroidogenesis in rat granulosa cells. To achieve this aim, inhibitors of PKA (PKAI), PI3K (wortmannin), and mTORC1 (rapamycin) were employed. PKAI and wortmannin suppressions of the FSH increased progesterone production were partly attributed to decreased level of 3beta-HSD, and their suppression of the FSH plus TGFbeta1 effect was attributed to the reduction of all the three key players, steroidogenic acute regulatory (StAR) protein, P450scc, and 3beta-HSD. Further, FSH activated the PI3K pathway including increased integrin-linked kinase (ILK) activity and phosphorylation of Akt(S473), mTOR(S2481), S6K(T389), and transcription factors particularly FoxO1(S256) and FoxO3a(S253), which were reduced by wortmannin treatment but not by PKAI. Interestingly, PKAI suppression of FSH-induced phosphorylation of cAMP regulatory element-binding protein (CREB(S133)) disappeared in the presence of wortmannin, suggesting that wortmannin may affect intracellular compartmentalization of signaling molecule(s). In addition, TGFbeta1 had no effect on FSH-activated CREB and PI3K signaling mediators. We further found that rapamycin reduced the TGFbeta1-enhancing effect of FSH-stimulated steroidogenesis, yet it exhibited no effect on FSH action. Surprisingly, rapamycin displayed a suppressive effect at concentrations that had no effect on mTORC1 activity. Together, this study demonstrates a delicate interplay between cAMP/PKA and PI3K signaling in FSH and TGFbeta1 regulation of steroidogenesis in rat granulosa cells. Furthermore, we demonstrate for the first time that TGFbeta1 acts in a rapamycin-hypersensitive and mTORC1-independent manner in augmenting FSH-stimulated steroidogenesis in rat granulosa cells. PMID- 17283242 TI - Disordered follicle development in ovaries of prenatally androgenized ewes. AB - Exposure to excess androgens in utero induces irreversible changes in gonadotrophin secretion and results in disrupted reproductive endocrine and ovarian function in adulthood, in a manner reminiscent of the common clinical endocrinopathy of polycystic ovary syndrome (PCOS). We have recently identified an abnormality in early follicle development in PCOS which we suggested might be an androgenic effect. We propose that altered ovarian function in androgenized ewes is due to prenatal androgens not only causing an abnormality of gonadotrophin secretion, but also exerting a direct effect on the early stages of folliculogenesis. Therefore, in this study, we explored the possible differences between small preantral follicles in the ovarian cortex of androgenized female lambs with those of normal lambs. At 8 months of age, small ovarian cortical biopsies (approximately 5 mm3) were obtained at laparotomy from nine female lambs that had been exposed to androgens in utero from embryonic days 30 to 90 of a 147 day pregnancy, and 11 control female lambs. Further, ovarian tissue was obtained at 20 months of age from ten androgenized and nine control animals. Tissue was either fixed immediately for histology or cultured for up to 15 days prior to fixing. The number of follicles in haematoxylin and eosin-stained sections was counted and recorded along with the stage of development. Before culture, the total follicle density (follicles/mm3 tissue) was not statistically significantly different between the two types of ovary at either 8 or 20 months of age. Furthermore, there were no statistically significant differences in the density of follicles at each stage of development. However, there was a lower percentage of primordial follicles, but a higher percentage of primary follicles, in biopsies taken at 8 months from androgenized lambs when compared with controls. At 20 months, the proportions of follicles at the primordial and primary stages were not significantly different between the two groups, but this was mainly attributable to an increase in the proportion of growing follicles in biopsies from control animals. Culture of ovarian cortex from 8-month-old lambs resulted in a progressive increase in the proportion of growing follicles when compared with tissue fixed on the day of surgery. However, there was no difference between androgenized and control tissue in the percentage of growing follicles. The increase in the proportion of growing follicles in the cortex of androgenized animals is reminiscent of similar observations in human polycystic ovaries and suggests that excess exposure to androgen in early life plays a part in the accelerated progression of follicle development from the primordial to the primary stage in polycystic ovaries. PMID- 17283243 TI - The influence of 17beta-estradiol on annexin 1 expression in the anterior pituitary of the female rat and in a folliculo-stellate cell line. AB - Annexin 1 (ANXA1) is a Ca2+- and phospholipid-binding protein that plays an important role as a mediator of glucocorticoid action in the host-defence and neuroendocrine systems. Sex differences in hypothalamo-pituitary-adrenal (HPA) axis activity are well documented and a number of studies have demonstrated that gonadal steroids act as regulators of HPA activity. The aim of this study was to investigate the effect of ovariectomy and 17beta-estradiol replacement, and estrous cycle stage, on anterior pituitary ANXA1 content. The amount of anterior pituitary ANXA1 determined by western blotting varied with estrous cycle stage with a peak at estrus declining to a trough at proestrus. Ovariectomy resulted in a significant (P<0 x 05) decrease in anterior pituitary ANXA1 content. Administration of 17beta-estradiol (1 microg/100 g) significantly (P<0 x 01) increased anterior pituitary ANXA1 expression in the ovariectomized animals. In contrast, there was no change in pituitary ANXA1 content in response to 17beta estradiol in adrenalectomized and adrenalectomized/ovariectomized rats. Treatment of TtT/GF cells, a folliculo-stellate cell line, with 17beta-estradiol (1 x 8-180 nM) increased ANXA1 mRNA expression and increased the amount of ANXA1 protein externalized in response to a dexamethasone stimulus. These results indicate that 17beta-estradiol stimulates ANXA1 expression in the anterior pituitary and in vivo an adrenal factor contributes to the mechanism of action. PMID- 17283244 TI - Regulation of the expression and secretion of urocortin 2 in rat pituitary. AB - We previously demonstrated that urocortin 2 (Ucn 2) is expressed in the proopiomelanocortin (POMC) cells of rat pituitary. However, the regulatory mechanism of pituitary synthesis and secretion of Ucn 2 remained to be clarified. We hypothesized that hypothalamic hormones and glucocorticoids may control the expression and secretion of pituitary Ucn 2, as Ucn 2 is expressed in POMC expressing cells in the pituitary. Thus, in the present study, we tested this hypothesis using primary culture of rat pituitary cells. The secretion of Ucn 2 from the anterior and intermediate pituitary cells was significantly increased by 50 mM KCl. In the anterior pituitary cells, corticotropin-releasing factor (CRF) increased mRNA expression levels and secretion of Ucn 2, although arginine vasopressin (AVP) did not induce any significant change in Ucn 2 expression or secretion. Under these conditions, both CRF and AVP increased ACTH secretion, but only CRF increased the level of POMC mRNA expression. Dexamethasone inhibited Ucn 2 and POMC mRNA expression levels, while it inhibited the secretion of only Ucn 2. In the intermediate pituitary, CRF increased both the mRNA expression levels and secretion of Ucn 2. Furthermore, dopamine did not affect either the mRNA expression level or secretion of Ucn 2 although it inhibited beta-endorphin secretion in the intermediate pituitary cells. These results suggest that the mRNA expression and secretion of Ucn 2 in POMC cells of the pituitary are positively regulated by CRF and negatively regulated by glucocorticoids. PMID- 17283245 TI - Glucocorticoid feedback control of corticotropin in the hypoxic neonatal rat. AB - The objective of this study was to determine the effects of manipulating glucocorticoid negative feedback on acute ACTH and corticosterone responses to corticotropin-releasing hormone (CRH) injection in 7-day-old rats exposed to normoxia or hypoxia from birth. Chemical adrenalectomy was achieved with aminoglutethimide, and glucocorticoids were replaced with a low dose of dexamethasone. Hypoxia per se increased basal plasma corticosterone and attenuated the plasma ACTH response to CRH. Aminoglutethimide per se decreased plasma corticosterone and strongly increased basal plasma ACTH and anterior pituitary POMC gene expression. Dexamethasone partially attenuated elevations in basal plasma ACTH due to aminoglutethimide in both normoxic and hypoxic pups, but inhibited anterior pituitary POMC expression and CRH-induced plasma ACTH only in hypoxic pups. Despite this inhibition, hypoxic pups treated with both dexamethasone and aminoglutethimide still exhibited a significant CRH-induced increment in plasma ACTH, which was lacking in hypoxic pups not treated with either dexamethasone or aminoglutethimide. We conclude that ACTH responses to acute stimuli in hypoxic neonatal rats are prevented by ACTH-independent increases in corticosterone, rather than by intrinsic hypothalamic-pituitary hypoactivity. PMID- 17283246 TI - CITED2 is expressed in human adrenocortical cells and regulated by basic fibroblast growth factor. AB - CITED2 gene deletion in mice leads to adrenal agenesis. Therefore, we analyzed CITED2, a CBP/p300 interacting transactivator with transforming activity, in the human adrenal gland. In this study, we examined CITED2 expression in human embryonic and adult adrenal glands as well as adrenocortical carcinomas. As ACTH and basic fibroblast growth factor (bFGF) are connected to the physiology and growth of adrenocortical cells we studied the regulation of CITED2 by these factors in the NCI-H295R adrenocortical carcinoma cell line. We found CITED2 expression in the adult adrenal cortex as well in adrenocortical carcinomas. At an early stage of human adrenal organogenesis CITED2 could be located to the definitive zone of the developing adrenal gland using immunohistochemistry. In NCI-H295R cells, stimulation by bFGF led to a dose-dependent increase in CITED2 promotor activity, mRNA and protein expression while ACTH had no significant effect. The stimulatory effect of bFGF could be reduced by blocking mitogen activated protein kinase activity using the MAPkinase kinase (MEK1)-inhibitor PD98059. CITED2 is expressed in embryonic and adult human adrenal glands as well as in adrenocortical cancer. It is connected to the signaling cascades of bFGF and its expression is modulated by mitogen-activated protein kinases. This suggests a novel role for CITED2 in human adrenal growth and possibly in adrenal tumorigenesis. PMID- 17283247 TI - Is siesta masking masked hypertension? PMID- 17283249 TI - Beta1 integrins modulate beta-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling. AB - Sympathetic nerve activity increases in the heart during cardiac failure. Here, we hypothesized that beta1 integrins play a protective role in chronic beta adrenergic receptor-stimulated cardiac myocyte apoptosis and heart failure. L isoproterenol (iso; 400 microg/kg per hour) was infused in a group of wild-type (WT) and beta1 integrin heterozygous knockout (hKO) mice. Left ventricular structural and functional remodeling was studied at 7 and 28 days of iso infusion. Western blot analysis demonstrated reduced beta1 integrin levels in the myocardium of hKO-sham. Iso-infusion increased heart weight:body weight ratios in both groups. However, the increase was significantly higher in WT-iso. M-mode echocardiography indicated increased left ventricular end-diastolic diameter, percentage of fractional shortening, and ejection fraction in the WT-iso group. The percentage of fractional shortening and ejection fraction were significantly lower in hKO-iso versus hKO-sham and WT-iso. Peak left ventricular developed pressure and left ventricular end-diastolic pressure measured using Langendorff perfusion analyses were significantly higher in the WT-iso group (P<0.05 versus WT-sham and hKO-Iso). The number of TUNEL-positive myocytes was significantly higher in hKO-iso hearts 7 and 28 days after iso-infusion. The increase in myocyte cross-sectional area and fibrosis was higher in the WT-iso group. Matrix metalloproteinase-9 protein levels were significantly higher in WT-iso, whereas matrix metalloproteinase-2 levels were increased in hKO-iso hearts. Iso-infusion increased phosphorylation of c-Jun N-terminal kinase and extracellular signal regulated kinase 1/2 in both groups. The increase in c-Jun N-terminal kinase phosphorylation was significantly higher in hKO-iso (P<0.001 versus WT-iso). Thus, beta1 integrins play a crucial role in beta-adrenergic receptor-stimulated myocardial remodeling with effects on cardiac myocyte hypertrophy, apoptosis, and left ventricular function. PMID- 17283250 TI - High blood pressure in pregnancy and coronary calcification. AB - A considerable proportion of pregnant women develop high blood pressure in pregnancy. Although it is assumed that this condition subsides after pregnancy, many of these women develop the metabolic syndrome later in life and are at increased risk to develop coronary heart disease. Atherosclerosis development is considered in between risk factors and occurrence of vascular symptoms. We set out to cross-sectionally study the relation of high blood pressure during pregnancy with risk of coronary calcification. The study population was composed 491 healthy postmenopausal women selected from a population-based cohort study. Information on high blood pressure during pregnancy was obtained using a questionnaire. Between 2004 and 2005, the women underwent a multidetector computed tomography (Philips Mx 8000 IDT 16) to assess coronary calcium. The Agatston score, volume, and mass measurements were used to quantify coronary calcium. A total of 30.7% of the women reported to have had high blood pressure in pregnancy. Body mass index (odds ratio [OR]: 1.05; 95% CI: 1.01 to 1.09) and diastolic blood pressure (OR: 1.03; 95% CI: 1.01 to 1.05) were significantly related to a history of high blood pressure in pregnancy. Age was significantly related to increased coronary calcification. Women with a history of high blood pressure during pregnancy had a 57% increased risk of having coronary calcification compared with those women without this condition (OR: 1.57; 95% CI: 1.04 to 2.37). After adjusting for age, the relation did not change (OR: 1.64; 95% CI: 1.07 to 2.53). We concluded that high blood pressure during pregnancy is associated with an increased risk of coronary calcification later in life. PMID- 17283251 TI - Molecular biology of the natriuretic peptide system: implications for physiology and hypertension. PMID- 17283253 TI - Sleepers versus nonsleepers: another twist to the dipper/nondipper concept. PMID- 17283252 TI - Role of N-acetyl-seryl-aspartyl-lysyl-proline in the antifibrotic and anti inflammatory effects of the angiotensin-converting enzyme inhibitor captopril in hypertension. AB - Angiotensin-converting enzyme inhibitors (ACEis) are known to have antifibrotic effects on the heart and kidney in both animal models and humans. N-acetyl-seryl aspartyl-lysyl-proline is a natural inhibitor of proliferation of hematopoietic stem cells and a natural substrate of ACEi that was reported to prevent cardiac and renal fibrosis in vivo. However, it is not clear whether N-acetyl-seryl aspartyl-lysyl-proline participates in the antifibrotic effects of ACEi. To clarify this issue, we used a model of aldosterone-salt-induced hypertension in rats treated with the ACEi captopril either alone or combined with an anti-N acetyl-seryl-aspartyl-lysyl-proline monoclonal antibody. These hypertensive rats had the following: (1) left ventricular and renal hypertrophy, as well as increased collagen deposition in the left ventricular and the kidney; (2) glomerular matrix expansion; and (3) increased ED1-positive cells and enhanced phosphorylated-p42/44 mitogen-activated protein kinase in the left ventricle and kidney. The ACEi alone significantly lowered systolic blood pressure (P=0.008) with no effect on organ hypertrophy; it significantly lowered left ventricular collagen content, and this effect was blocked by the monoclonal antibody as confirmed by the histological data. As expected, the ACEi significantly decreased renal collagen deposition and glomerular matrix expansion, and these effects were attenuated by the monoclonal antibody. Likewise, the ACEi significantly decreased ED1-positive cells and inhibited p42/44 mitogen-activated protein kinase phosphorylation in the left ventricle and kidney, and these effects were blocked by the monoclonal antibody. We concluded that in aldosterone-salt-induced hypertension, the antifibrotic effect of ACEi on the heart and kidney, is partially mediated by N-acetyl-seryl-aspartyl-lysyl-proline, resulting in decreased inflammatory cell infiltration and p42/44 mitogen-activated protein kinase activation. PMID- 17283254 TI - Less atherosclerosis and lower blood pressure for a meaningful life perspective with more brain. PMID- 17283255 TI - Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. AB - BACKGROUND: Although the participation of inflammation in atherogenesis is widely recognized, the identification of the different components has not been clarified. In particular, the role of inflammation in plaque destabilization is not fully understood. METHODS AND RESULTS: Our main findings were as follows: (1) In a microarray experiment, we identified visfatin, one of the most recently identified adipokines, as a gene that was markedly enhanced in carotid plaques from symptomatic compared with plaques from asymptomatic individuals. This finding was confirmed when carotid plaques from 7 patients with asymptomatic and 14 patients with symptomatic lesions were examined with real-time reverse transcription polymerase chain reaction. (2) Immunohistochemistry showed that visfatin was localized in areas that were rich in lipid-loaded macrophages. (3) The relationship between visfatin and unstable lesions was also found in patients with coronary artery disease, demonstrating a strong visfatin immunostaining in lipid-rich regions within the material obtained at the site of plaque rupture in patients with acute myocardial infarction. (4) Both oxidized low-density lipoprotein and tumor necrosis factor-alpha increased visfatin expression in THP 1 monocytes, with a particularly enhancing effect when these stimuli were combined. (5) Visfatin increased matrix metalloproteinase-9 activity in THP-1 monocytes and tumor necrosis factor-alpha and interleukin-8 levels in peripheral blood mononuclear cells. Both of these effects were abolished when insulin receptor signaling was blocked. CONCLUSIONS: Our findings suggest that visfatin should be regarded as an inflammatory mediator, localized to foam cell macrophages within unstable atherosclerotic lesions, that potentially plays a role in plaque destabilization. PMID- 17283256 TI - An alpha1A-adrenergic-extracellular signal-regulated kinase survival signaling pathway in cardiac myocytes. AB - BACKGROUND: In alpha1-AR knockout (alpha1ABKO) mice that lacked cardiac myocyte alpha1-adrenergic receptor (alpha1-AR) binding, aortic constriction induced apoptosis, dilated cardiomyopathy, and death. However, it was unclear whether these effects were attributable to a lack of cardiac myocyte alpha1-ARs and whether the alpha1A, alpha1B, or both subtypes mediated protection. Therefore, we investigated alpha1A and alpha1B subtype-specific survival signaling in cultured cardiac myocytes to test for a direct protective effect of alpha1-ARs in cardiac myocytes. METHODS AND RESULTS: We cultured alpha1ABKO myocytes and reconstituted alpha1-AR signaling with adenoviruses expressing alpha1-GFP fusion proteins. Myocyte death was induced by norepinephrine, doxorubicin, or H2O2 and was measured by annexin V/propidium iodide staining. In alpha1ABKO myocytes, all 3 stimuli significantly increased apoptosis and necrosis. Reconstitution of the alpha1A subtype, but not the alpha1B, rescued alpha1ABKO myocytes from cell death induced by each stimulus. To address the mechanism, we examined alpha1-AR activation of extracellular signal-regulated kinase (ERK). In alpha1ABKO hearts, aortic constriction failed to activate ERK, and in alpha1ABKO myocytes, expression of a constitutively active MEK1 rescued alpha1ABKO myocytes from norepinephrine-induced death. In addition, only the alpha1A-AR activated ERK in alpha1ABKO myocytes, and expression of a dominant-negative MEK1 completely blocked alpha1A survival signaling in alpha1ABKO myocytes. CONCLUSIONS: Our results demonstrate a direct protective effect of the alpha1A subtype in cardiac myocytes and define an alpha1A-ERK signaling pathway that is required for myocyte survival. Absence of the alpha1A-ERK pathway can explain the failure to activate ERK after aortic constriction in alpha1ABKO mice and can contribute to the development of apoptosis, dilated cardiomyopathy, and death. PMID- 17283257 TI - C-reactive protein causes downregulation of vascular angiotensin subtype 2 receptors and systolic hypertension in mice. AB - BACKGROUND: Chronic elevations in circulating C-reactive protein (CRP) are associated with a greater risk of hypertension. Whether elevations in CRP cause hypertension is unknown. METHODS AND RESULTS: Chronic, conscious blood pressure (BP) measurements were performed by radiotelemetry in wild-type CF1 control and CF1 transgenic mice expressing rabbit CRP (CF1-CRP) under the regulation of the phosphoenolpyruvate carboxykinase promoter. Compared with controls, CF1-CRP mice had hypertension that was predominantly systolic, and the severity of hypertension varied in parallel with changes in CRP levels modulated by dietary manipulation. Mice that were hemizygous for the transgene with CRP levels of 9 microg/mL were also hypertensive, indicating that modest elevations in CRP are sufficient to alter BP. CRP transgenic mice had exaggerated BP elevation in response to angiotensin II and a reduction in vascular angiotensin receptor subtype 2 (AT2) expression. In contrast, the decline in BP with angiotensin receptor subtype 1 (AT1) antagonism and vascular AT1 abundance were unaltered, which indicates a selective effect of CRP on AT2. Ex vivo experiments further showed that the CRP-induced decrease in AT2 is a direct effect on the vascular wall, not requiring systemic responses, and that it is reversed by an NO donor, which indicates a role for NO deficiency in the process. In parallel, the chronic inhibition of NO synthase in wild-type mice attenuated vascular AT2 expression without affecting AT1. CONCLUSIONS: These findings provide direct evidence for CRP-induced hypertension, and they further identify a novel underlying mechanism involving downregulation of AT2 related to NO deficiency. PMID- 17283258 TI - Certificate of need regulation and cardiac catheterization appropriateness after acute myocardial infarction. AB - BACKGROUND: Certificate of need (CON) regulation was introduced to control healthcare costs and improve quality of care in part by limiting the number of facilities providing complex medical care. Our objective was to examine whether rates of appropriate cardiac catheterization after admission for acute myocardial infarction varied between states with and without CON regulation of cardiac catheterization. METHODS AND RESULTS: We performed a retrospective analysis of chart-abstracted data for 137,279 Medicare patients admitted for acute myocardial infarction between 1994 and 1996 at 4179 US acute-care hospitals. Using 3-level hierarchical generalized linear modeling adjusted for patient sociodemographic and clinical characteristics and physician and hospital characteristics, we compared catheterization rates within 60 days of admission for states (and the District of Columbia) with (n=32) and without (n=19) CON regulation in the full cohort and stratified by catheterization appropriateness. Appropriateness was categorized as strongly, equivocally, or weakly indicated. We found CON regulation was associated with a borderline-significant lower rate of catheterization overall (45.8% versus 46.5%; adjusted risk ratio [RR] 0.91, 95% confidence interval 0.82 to 1.00, P=0.06). After stratification by appropriateness, CON regulation was not associated with a significantly lower rate of catheterization among 63,823 patients with strong indications (49.9% versus 50.3%; adjusted RR 0.94, 95% confidence interval 0.86 to 1.02, P=0.17). However, CON regulation was associated with significantly lower rates of catheterization among 65,077 patients with equivocal indication (45.0% versus 46.0%; adjusted RR 0.88, 95% confidence interval 0.78 to 1.00, P=0.05) and among 8379 patients with weak indications (19.8% versus 21.8%; adjusted RR 0.84, 95% confidence interval 0.71 to 0.98, P=0.04). Associations were weakened substantially after adjustment for hospital coronary artery bypass graft surgery or cardiac catheterization capability. CONCLUSIONS: CON regulation was associated with modestly lower rates of equivocally and weakly indicated cardiac catheterization after admission for acute myocardial infarction, but no significant differences existed in rates of strongly indicated catheterization. PMID- 17283259 TI - Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. AB - BACKGROUND: Ex vivo expansion of resident cardiac stem cells, followed by delivery to the heart, may favor regeneration and functional improvement. METHODS AND RESULTS: Percutaneous endomyocardial biopsy specimens grown in primary culture developed multicellular clusters known as cardiospheres, which were plated to yield cardiosphere-derived cells (CDCs). CDCs from human biopsy specimens and from comparable porcine samples were examined in vitro for biophysical and cytochemical evidence of cardiogenic differentiation. In addition, human CDCs were injected into the border zone of acute myocardial infarcts in immunodeficient mice. Biopsy specimens from 69 of 70 patients yielded cardiosphere-forming cells. Cardiospheres and CDCs expressed antigenic characteristics of stem cells at each stage of processing, as well as proteins vital for cardiac contractile and electrical function. Human and porcine CDCs cocultured with neonatal rat ventricular myocytes exhibited biophysical signatures characteristic of myocytes, including calcium transients synchronous with those of neighboring myocytes. Human CDCs injected into the border zone of myocardial infarcts engrafted and migrated into the infarct zone. After 20 days, the percentage of viable myocardium within the infarct zone was greater in the CDC-treated group than in the fibroblast-treated control group; likewise, left ventricular ejection fraction was higher in the CDC-treated group. CONCLUSIONS: A method is presented for the isolation of adult human stem cells from endomyocardial biopsy specimens. CDCs are cardiogenic in vitro; they promote cardiac regeneration and improve heart function in a mouse infarct model, which provides motivation for further development for therapeutic applications in patients. PMID- 17283260 TI - Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE). AB - BACKGROUND: Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes. METHODS AND RESULTS: A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with > or = 1 episode of myocardial ischemia that lasted > or = 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months. The primary efficacy parameter (absolute change from baseline in total duration of ischemia at month 12) was significantly reduced in both groups at month 3 and month 12 (both P<0.001 for each treatment group) with no significant difference between the treatment groups. Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients, a trend toward fewer major acute cardiovascular events (hazard ratio, 0.71; 95% confidence interval, 0.46, 1.09; P=0.114), and a significantly greater reduction in all cause death (hazard ratio, 0.33; 95% confidence interval, 0.13, 0.83; P=0.014). CONCLUSIONS: Compared with moderate pravastatin therapy, intensive atorvastatin therapy was associated with reductions in cholesterol, major acute cardiovascular events, and death in addition to the reductions in ischemia observed with both therapies. The contrast between the therapies' differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol lowering thresholds for ischemia and major acute cardiovascular events may differ. The Study Assessing Goals in the Elderly (SAGE) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy. PMID- 17283262 TI - Preoperative posterior leaflet angle accurately predicts outcome after restrictive mitral valve annuloplasty for ischemic mitral regurgitation. AB - BACKGROUND: Ischemic mitral regurgitation (MR) often persists after restrictive mitral valve annuloplasty, in which case it is associated with worse clinical outcomes. The goal of the present study was to determine whether persistence of MR and/or clinical outcome could be predicted from preoperative analysis of mitral valve configuration. METHODS AND RESULTS: In 51 consecutive patients undergoing restrictive annuloplasty for ischemic MR, posterior leaflet (PL) angle, anterior leaflet angle, coaptation distance, and tenting area were quantified by echocardiography before surgery (6+/-3 days), and MR severity was assessed before and early after surgery (9+/-4 days). Postoperatively, persistence of mild to moderate MR (vena contracta > 3 mm) was observed in 11 (22%) of the patients. The best predictor of postoperative persistence of MR was a PL angle > or = 45 degrees (sensitivity 100%, specificity 97%, positive predictive value 92%, negative predictive value 100%). Patients with persistent MR had markedly lower 3-year event-free survival (26+/-20%) compared with those with nonpersistent MR (75+/-12%, P=0.01). Preoperative presence of a PL angle > or = 45 degrees also was associated with a markedly lower 3-year event-free survival (22+/-17% versus 76+/-12%; P<0.001). CONCLUSIONS: In patients undergoing restrictive annuloplasty for ischemic MR, persistence of MR and 3-year event-free survival can accurately be predicted by preoperative analysis of mitral valve configuration. Patients with a PL angle > or = 45 degrees (ie, with high PL restriction) should thus be considered poor candidates for this procedure, and concomitant or alternative procedures should be contemplated. PMID- 17283261 TI - Prognostic value of growth-differentiation factor-15 in patients with non-ST elevation acute coronary syndrome. AB - BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non-ST-elevation acute coronary syndrome. METHODS AND RESULTS: Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non-ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF 15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P<0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N terminal pro-B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro-B type natriuretic peptide, C-reactive protein, and creatinine clearance. CONCLUSIONS: GDF-15 is a new biomarker of the risk for death in patients with non ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers. PMID- 17283263 TI - Consistently stable or decreased body mass index in young adulthood and longitudinal changes in metabolic syndrome components: the Coronary Artery Risk Development in Young Adults Study. AB - BACKGROUND: Data are sparse regarding the association of stable body mass index (BMI) over the long term with metabolic syndrome components in young adults. METHODS AND RESULTS: Participants in the Coronary Artery Risk Development in Young Adults Study, including white and black adults 18 to 30 years of age at the initial examination in 1985 to 1986, were stratified into groups by baseline BMI and change in BMI (stable/decreased, increased >2 kg/m2, or fluctuating) across all 6 examinations between years 0 and 15 of the study. Changes in metabolic syndrome components were compared between groups. Among 1358 men and 1321 women, 16.3% maintained a stable BMI, 73.9% had an increased BMI, and 9.8% had a fluctuating BMI. Over 15 years, participants with stable BMI had essentially unchanged levels of metabolic syndrome components, regardless of baseline BMI, whereas those with increased BMI had progressively worsening levels. For example, men with a baseline BMI of 20.0 to 24.9 kg/m2 and stable BMI during follow-up had a mean increase of only 15 mg/dL in fasting triglycerides over 15 years compared with 65 mg/dL (P<0.001) in those whose BMI increased. Incidence of metabolic syndrome at year 15 was lower in the stable BMI group (2.2%) compared with the increased BMI group (18.8%; P<0.001). CONCLUSIONS: Adverse progression of metabolic syndrome components with advancing age may not be inevitable. Young adults who maintained stable BMI over time had minimal progression of risk factors and lower incidence of metabolic syndrome regardless of baseline BMI. Greater public health efforts should be aimed at long-term weight stabilization. PMID- 17283264 TI - C-reactive protein and prediction of coronary heart disease and global vascular events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). AB - BACKGROUND: The role of C-reactive protein (CRP) in predicting vascular events and response to statin therapy remains uncertain. Additional large prospective studies are required. METHODS AND RESULTS: Baseline CRP was related to risk over 3.2 years for primary a combined end point (definite or suspected death from coronary heart disease, nonfatal myocardial infarction, and fatal or nonfatal stroke; n=865 events) and secondary (coronary heart disease events or stroke alone) and tertiary (stroke plus transient ischemic attack) end points in the Prospective Study of Pravastatin in the Elderly at Risk (n=5804 men and women; age, 70 to 82 years). CRP levels were higher in subjects who had a subsequent primary end-point event compared with those who did not (geometric mean; 3.64 mg/L [SD, 3.08 mg/L] versus 3.01 mg/L [SD, 3.05 mg/L]; P<0.0001). CRP correlated positively with body mass index and smoking status and negatively with high density lipoprotein cholesterol. The unadjusted hazard ratio for the primary end point was 1.48 (95% CI, 1.26 to 1.74) in a comparison of top and bottom thirds for CRP, falling to 1.36 (95% CI, 1.15 to 1.61) with adjustment for established predictors and body mass index. Similar results were obtained for other end points or when results were examined separately by history of vascular disease. However, baseline CRP added minimally to risk prediction beyond conventional predictors and did not relate to the magnitude of pravastatin benefit. CONCLUSIONS: Elevated CRP minimally enhances cardiovascular disease prediction beyond established vascular risk factors and does not predict response to statin therapy in elderly subjects at risk. These data suggest that CRP has limited clinical value in cardiovascular disease risk stratification or predicting response to statin therapy in elderly people. PMID- 17283265 TI - Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction. AB - BACKGROUND: The pathophysiology of diastolic heart failure (DHF) is poorly understood. One potential explanation is an active fibrotic process that produces increased ventricular stiffness, which compromises filling. The present study investigates collagen metabolism in hypertensive patients in different phases of diastolic function with and without proven DHF. METHODS AND RESULTS: We studied 86 hypertensive patients divided into groups according to the presence of DHF (32 with, 54 without) and phase of diastolic function (20 with normal function, 38 with impaired relaxation, 10 with pseudonormalization, and 16 with restrictive like filling). Serum carboxy-terminal, amino-terminal, and carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, matrix metalloproteinases (MMPs; total MMP-1, active MMP-2, and MMP-9), and tissue inhibitor of MMPs levels were assayed by radioimmunoassay and ELISA. Doppler-echocardiographic assessment of diastolic filling was made with measurements of E/A ratio, E-wave deceleration time, and isovolumic relaxation time. Serum carboxy-terminal telopeptide of procollagen type I, carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 levels (P<0.001 for all, controlled for age and gender) were greater in patients with DHF than in those without. When we controlled for age and gender, levels of serum carboxy-terminal telopeptide of procollagen type I, tissue inhibitor of MMP-1, amino-terminal propeptide of procollagen type III (all P<0.001), carboxy-terminal telopeptide of procollagen type I (P=0.008), and MMP-2 (P=0.03) were greater in more severe phases of diastolic dysfunction. Within phases of diastolic dysfunction, serum carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 were elevated in those with DHF compared with those without DHF (all P<0.001). CONCLUSIONS: These data demonstrate serological evidence of an active fibrotic process in DHF, which is more marked in more severe diastolic dysfunction. This observation may help explain the pathophysiology of DHF and may suggest new avenues for diagnostic and therapeutic intervention. PMID- 17283266 TI - Influence of hospital procedural volume on care process and mortality for patients undergoing elective surgery for mitral regurgitation. AB - BACKGROUND: Few studies have examined the procedural volume-outcome relationship for heart valve surgery. None have examined process of care factors that may be mediators of this association. METHODS AND RESULTS: This was a retrospective review of outcomes for 13,614 patients having elective surgery for mitral regurgitation between 2000 and 2003 in 575 North American centers participating in the Society of Thoracic Surgeons National Cardiac Database. Hospital annual mitral valve volume varied widely from 22 cases per year in the lowest-volume quartile to 394 in the highest. Unadjusted mortality rates decreased from 3.08% in the lowest-volume category to 1.11% in the highest-volume category. The risk adjusted odds ratio for mortality in the highest-volume category compared with the lowest was 0.48 (95% confidence interval 0.28 to 0.82). The rates of mitral valve repair increased from 47.7% in the lowest-volume quartile to 77.4% in high volume hospitals (P<0.0001). Similarly, the rates of bioprosthetic valve use for patients aged >65 years rose from 59% in the lowest-volume quartile to 75% in the highest-volume quartile (P=0.0002). The association between volume and mortality was still significant but attenuated when the risk adjustment was modified to adjust for mitral valve repair versus replacement. CONCLUSIONS: Hospital procedural volume was associated with higher frequency of valve repair, higher frequency of prosthetic valve usage in elderly patients, and lower adjusted operative mortality. Differences in care process may contribute to improved outcomes in higher-volume centers. PMID- 17283267 TI - Risk index for perioperative renal dysfunction/failure: critical dependence on pulse pressure hypertension. AB - BACKGROUND: An acute renal event after coronary bypass graft surgery is associated with high mortality and substantial additive cost. METHODS AND RESULTS: This prospective and descriptive study of 4801 patients having coronary bypass graft surgery with cardiopulmonary bypass from November 1996 to June 2000 at 70 centers in 16 countries established associations between predictor variables and postoperative renal composite (renal dysfunction and/or renal failure) from a cohort of 2381 patients and developed a risk index assessed in a validation cohort of 2420 patients. Postoperative renal composite occurred in 231 patients (4.8%). Independent and significant risk factors were age >75 years (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.23 to 3.37; P=0.006), preoperative congestive heart failure (OR, 2.38; CI, 1.55 to 3.64; P<0.001), prior myocardial infarction (OR, 1.75; CI, 1.08 to 2.83; P=0.023), preexisting renal disease (OR, 3.71; CI, 2.41 to 5.70; P<0.001), intraoperative multiple inotrope use (OR, 2.75; CI, 1.75 to 4.31; P<0.001), intraoperative intra-aortic balloon pump insertion (OR, 4.41; CI, 2.21 to 8.80; P<0.001), cardiopulmonary bypass >2 hours (OR, 1.78; CI, 1.15 to 2.74; P=0.01), and preoperative pulse pressure such that for every additional 20-mm Hg increment in pulse pressure >40 mm Hg, there was an OR of 1.49 (CI, 1.17 to 1.89; P=0.001). Patients with pulse pressure hypertension >80 mm Hg were 3 times more likely to die a renal-related death compared with those without (3.7% versus 1.1%). CONCLUSIONS: Beside established risk factors, pulse pressure is independently and significantly associated with increased renal composite. PMID- 17283269 TI - Apical ballooning syndrome: an important differential diagnosis of acute myocardial infarction. PMID- 17283268 TI - Impact of patient and target-vessel characteristics on arterial and venous bypass graft patency: insight from a randomized trial. AB - BACKGROUND: The purpose of this investigation was to determine optimal patient and target-vessel characteristics to maximize arterial and venous graft patency on the basis of data from a large clinical trial. METHODS AND RESULTS: Angiographic data on 440 radial artery grafts and 440 saphenous vein grafts were analyzed with methodology to account for within-patient clustering. Multivariable models that incorporated patient demographic, operative, anatomic, and postdischarge medical management were constructed to determine predictors of graft occlusion. Radial artery use was strongly protective against graft occlusion at 1 year after adjustment for all covariates, with a larger protective effect seen in women (P=0.05 for a subgroup-by-treatment interaction). Among all grafts, diabetes and small target-vessel diameter were associated with an increased risk of graft occlusion, and grafting to a target vessel with more severe proximal stenosis was associated with a decreased risk of graft occlusion. With regard to gender, radial artery graft occlusion at 1 year occurred in similar proportions of men (8.6%) and women (5.3%, P=0.6), whereas, for saphenous vein grafts the comparable occlusion rates were 12.0% and 23.3% respectively (P=0.02). A history of peripheral vascular disease was associated with an elevated risk of radial artery occlusion but was not associated with early vein graft occlusion (P=0.02 for a subgroup-by-treatment interaction). CONCLUSIONS: Patients benefit from radial artery-coronary artery bypass conduits as opposed to saphenous vein conduits, and this effect is especially strong in women. Small target-vessel size adversely affected graft patency, and grafting to a target vessel with more severe proximal stenosis improved graft patency. PMID- 17283270 TI - Images in cardiovascular medicine. Left ventricular aneurysm associated with mucopolysaccharidosis type VI syndrome (Maroteaux-Lamy syndrome). PMID- 17283272 TI - Images in cardiovascular medicine. An unusual cause of hand cellulitis. PMID- 17283271 TI - Images in cardiovascular medicine. Tricyclic cardiotoxicity treated with sodium bicarbonate. PMID- 17283273 TI - Letter by Pieroni et al regarding article, "Contrast-enhanced magnetic resonance imaging of a patient with chloroquine-induced cardiomyopathy confirmed by endomyocardial biopsy". PMID- 17283274 TI - A view from Egypt. PMID- 17283275 TI - Far-fetched benefit of inflammation. PMID- 17283276 TI - Peripheral endovascular revascularization: some proof in the pudding? PMID- 17283278 TI - Effects of normal blood pressure, prehypertension, and hypertension on coronary microvascular function. AB - BACKGROUND: The assessment of coronary flow reserve (CFR) by transthoracic Doppler echocardiography has recently been introduced into clinical practice, and reduced CFR has been suggested to be a sensitive indicator of hypertensive end organ damage; however, to date, this methodology has not been used to evaluate CFR in subjects with prehypertension. Accordingly, the present study was designed to evaluate CFR in subjects with prehypertension. METHODS AND RESULTS: We measured CFR of 40 subjects with prehypertension, 60 patients with hypertension, and 50 normotensive healthy volunteers using transthoracic Doppler echocardiography. None of the subjects had any systemic disease. Age, gender, body mass index, heart rate, lipid profiles, fasting glucose levels, and hemoglobin were similar among the 3 groups. CFR was significantly lower in the hypertension group than in the prehypertension and control groups; in addition, it was significantly lower in subjects with prehypertension than in control subjects (2.23+/-0.47, 2.54+/-0.48, and 2.91+/-0.53, respectively). Furthermore, we found that prehypertension (beta=-0.31, P<0.01) and hypertension (beta=-0.57, P<0.01) were significant predictors of lower CFR in a multivariable model that adjusted for other variables. CFR was significantly and inversely correlated with age (r=-0.20, P=0.01), systolic blood pressure (r=-0.51, P<0.01), diastolic blood pressure (r=-0.47, P<0.01), high-sensitivity C-reactive protein levels (r=-0.21, P=0.01), left atrium diameter (r=-0.22, P<0.01), mitral E deceleration time (r= 0.19, P=0.02), and mitral A velocity (r=-0.27, P<0.01), whereas mitral E/A ratio was significantly and positively correlated with CFR (r=0.26, P<0.01). CONCLUSIONS: CFR is impaired in subjects with prehypertension, but this impairment is not as severe as that in hypertension. PMID- 17283277 TI - Critical role of monocyte chemoattractant protein-1/CC chemokine ligand 2 in the pathogenesis of ischemic cardiomyopathy. AB - BACKGROUND: Cardiac interstitial fibrosis plays an important role in the pathogenesis of ischemic cardiomyopathy, contributing to systolic and diastolic dysfunction. We have recently developed a mouse model of fibrotic noninfarctive cardiomyopathy due to brief repetitive myocardial ischemia and reperfusion. In this model, fibrotic changes are preceded by marked and selective induction of the CC chemokine monocyte chemoattractant protein-1 (MCP-1). We hypothesized that MCP-1 may mediate fibrotic remodeling through recruitment of mononuclear cells and direct effects on fibroblasts. METHODS AND RESULTS: Wild-type (WT) and MCP-1 null mice underwent daily 15-minute coronary occlusions followed by reperfusion. Additional WT animals received intraperitoneal injections of a neutralizing anti MCP-1 antibody after the end of each ischemic episode. Hearts were examined echocardiographically and processed for histological and RNA studies. WT mice undergoing repetitive brief myocardial ischemia and reperfusion protocols exhibited macrophage infiltration after 3 to 5 days and marked interstitial fibrosis in the ischemic area after 7 days, accompanied by ventricular dysfunction. MCP-1-null mice had markedly diminished interstitial fibrosis, lower macrophage infiltration, and attenuated ventricular dysfunction compared with WT animals. MCP-1 neutralization also inhibited interstitial fibrosis, decreasing left ventricular dysfunction and regional hypocontractility. Cardiac myofibroblasts isolated from WT but not from MCP-1-null animals undergoing repetitive myocardial ischemia and reperfusion demonstrated enhanced proliferative capacity. However, MCP-1 stimulation did not induce cardiac myofibroblast proliferation and did not alter expression of fibrosis-associated genes. CONCLUSIONS: Defective MCP-1 signaling inhibits the development of ischemic fibrotic cardiomyopathy in mice. The profibrotic actions of MCP-1 are associated with decreased macrophage recruitment and may not involve direct effects on cardiac fibroblasts. PMID- 17283279 TI - Contemporary pacemaker and defibrillator device therapy: challenges confronting the general cardiologist. PMID- 17283280 TI - Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. PMID- 17283281 TI - Georgia O'Keeffe at 291. PMID- 17283282 TI - Increased temporal and prefrontal activity in response to semantic associations in schizophrenia. AB - CONTEXT: Loosening of associations has long been considered a core feature of schizophrenia, but its neural correlate remains poorly understood. OBJECTIVE: To test the hypothesis that, in comparison with healthy control subjects, patients with schizophrenia show increased neural activity within inferior prefrontal and temporal cortices in response to directly and indirectly semantically related (relative to unrelated) words. DESIGN: A functional neuroimaging study using a semantic priming paradigm. SETTING: Lindemann Mental Health Center, Boston, Mass. PARTICIPANTS: Seventeen right-handed medicated outpatients with chronic schizophrenia and 15 healthy volunteers, matched for age and parental socioeconomic status. INTERVENTIONS: Functional magnetic resonance imaging as participants viewed directly related, indirectly related, and unrelated word pairs and performed a lexical decision task. MAIN OUTCOME MEASURES: Event-related functional magnetic resonance imaging measures of blood oxygenation level dependent activity (1) within a priori temporal and prefrontal anatomic regions of interest and (2) at all voxels across the cortex. RESULTS: Patients and controls showed no behavioral differences in priming but opposite patterns of hemodynamic modulation in response to directly related (relative to unrelated) word pairs primarily within inferior prefrontal cortices, and to indirectly related (relative to unrelated) word pairs primarily within temporal cortices. Whereas controls showed the expected decreases in activity in response to semantic relationships (hemodynamic response suppression), patients showed inappropriate increases in response to semantic relationships (hemodynamic response enhancement) in many of the same regions. Moreover, hemodynamic response enhancement within the temporal fusiform cortices to indirectly related (relative to unrelated) word pairs predicted positive thought disorder. CONCLUSION: Medicated patients with chronic schizophrenia, particularly those with positive thought disorder, show inappropriate increases in activity within inferior prefrontal and temporal cortices in response to semantic associations. PMID- 17283283 TI - Effects of gamma-aminobutyric acid-modulating drugs on working memory and brain function in patients with schizophrenia. AB - CONTEXT: Cognitive impairment causes morbidity in schizophrenia and could be due to abnormalities of cortical interneurons using the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). OBJECTIVES: To test the predictions that cognitive and brain functional responses to GABA-modulating drugs are correlated and abnormal in schizophrenia. DESIGN: Pharmacological functional magnetic resonance imaging study of 2 groups, each undergoing scanning 3 times, using an N back working memory task, after placebo, lorazepam, or flumazenil administration. SETTING AND PARTICIPANTS: Eleven patients with chronic schizophrenia were recruited from a rehabilitation service, and 11 healthy volunteers matched for age, sex, and premorbid IQ were recruited from the local community. Intervention Participants received 2 mg of oral lorazepam, a 0.9-mg intravenous flumazenil bolus followed by a flumazenil infusion of 0.0102 mg/min, or oral and intravenous placebo. MAIN OUTCOME MEASURES: Working memory performance was summarized by the target discrimination index at several levels of difficulty. Increasing (or decreasing) brain functional activation in response to increasing task difficulty was summarized by the positive (or negative) load response. RESULTS: Lorazepam impaired performance and flumazenil enhanced it; these cognitive effects were more salient in schizophrenic patients. Functional magnetic resonance imaging demonstrated positive load response in a frontoparietal system and negative load response in the temporal and posterior cingulate regions; activation of the frontoparietal cortex was positively correlated with deactivation of the temporocingulate cortex. After placebo administration, schizophrenic patients had abnormally attenuated activation of the frontoparietal cortex and deactivation of the temporocingulate cortex; this pattern was mimicked in healthy volunteers and exacerbated in schizophrenic patients by lorazepam. However, in schizophrenic patients, flumazenil enhanced deactivation of the temporocingulate and activation of the anterior cingulate cortices. CONCLUSIONS: The GABA-modulating drugs differentially affect working memory performance and brain function in schizophrenia. Cognitive impairment in schizophrenia may reflect abnormal inhibitory function and could be treated by drugs targeting GABA neurotransmission. PMID- 17283284 TI - Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia. AB - CONTEXT: Tardive dyskinesia (TD) is a common and potentially disabling disorder induced by use of antipsychotic drugs for which medical treatment often gives disappointing results. OBJECTIVE: To assess the efficacy of bilateral deep brain stimulation of the internal part of the globus pallidus to treat severe TD. DESIGN: Prospective phase 2 multicenter study. SETTING: Six French university hospitals. Patients Patients with severe TD refractory to medical treatment were studied to evaluate the severity of abnormal involuntary movements before and after 6 months of bilateral globus pallidus deep brain stimulation. A 2-step open Fleming procedure was used to avoid unnecessary accrual of patients. A successful outcome was defined as a decrease of more than 40% in the main outcome measure at 6 months. The early stopping rule was invoked if the number of successful outcomes in 10 patients was fewer than 2, or 5 or more. A double-blind evaluation in the presence and absence of stimulation was performed at 6 months after surgery. Main Outcome Measure Change in score on the Extrapyramidal Symptoms Rating Scale. RESULTS: At 6 months after surgery, the Extrapyramidal Symptoms Rating Scale score had decreased compared with baseline by more than 40% (mean improvement, 61%; range, 44%-75%) in the first 10 patients included. In accord with the 2-step open Fleming procedure, we ended the trial at the first step and concluded that pallidal stimulation is an effective treatment for TD. The efficacy of the treatment was confirmed by a double-blind evaluation, with a mean decrease of 50% (range, 30%-66%) (P = .002) in the Extrapyramidal Symptoms Rating Scale score when stimulation was applied compared with the absence of stimulation. There were no marked changes in the patients' psychiatric status. CONCLUSION: Although these results need to be confirmed in a larger group of patients with a longer follow-up, bilateral globus pallidus deep brain stimulation seems to offer a much-needed new treatment option for disabling TD. PMID- 17283286 TI - Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. AB - CONTEXT: Increasing evidence indicates that major depressive disorder (MDD) is associated with altered function of the major excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. A recently developed magnetic resonance spectroscopy method allows for reliable measurement of glutamate/glutamine (Glx) and GABA concentrations in prefrontal brain regions that have been implicated in the pathophysiologic mechanisms of MDD by studies using other neuroimaging and postmortem techniques. OBJECTIVE: To measure Glx and GABA levels in 2 regions of the prefrontal brain tissue in unmedicated adults with MDD. DESIGN: Cross-sectional study for association. SETTING: Psychiatric outpatient clinic. PARTICIPANTS: Twenty unmedicated, depressed patients with MDD and 20 age- and sex-matched controls. Intervention Participants underwent scanning using a 3-T whole-body scanner with a transmit receive head coil, providing a homogeneous radiofrequency field and the capability of obtaining spectroscopic measurements in a dorsomedial/dorsal anterolateral prefrontal region of interest (ROI) and a ventromedial prefrontal ROI. MAIN OUTCOME MEASURES: Glx and GABA levels derived from magnetic resonance spectroscopy signals. RESULTS: Depressed patients had reduced Glx levels in both ROIs. The GABA levels were reduced in the dorsomedial/dorsal anterolateral prefrontal ROI. Levels of GABA and Glx were positively correlated in both ROIs. CONCLUSIONS: For the first time, GABA and Glx concentrations were compared between unmedicated depressed adults and controls in prefrontal ROIs. The abnormal reductions in Glx and GABA concentrations found in the MDD sample were compatible with findings from postmortem histopathologic studies, indicating that glial cell density is reduced in the same areas in MDD. PMID- 17283285 TI - Neural and genetic correlates of antidepressant response to sleep deprivation: a functional magnetic resonance imaging study of moral valence decision in bipolar depression. AB - CONTEXT: Total sleep deprivation combined with light therapy causes rapid amelioration of bipolar depression. A polymorphism in the promoter for the serotonin transporter influences both antidepressant response and the structure and function of specific brain areas. OBJECTIVE: To determine whether antidepressant therapy or the genotype of the serotonin transporter influence the pattern of neural response to a task targeting the depressive biases in information processing (moral valence decision). DESIGN: Before-and-after trial studying the biologic correlates of response to treatment. SETTING: University hospital. Patients Twenty inpatients with bipolar depression. Intervention Repeated total sleep deprivation combined with light therapy for 1 week. MAIN OUTCOME MEASURES: Brain blood oxygen level-dependent functional magnetic resonance imaging using a 3.0-T scanner before and after treatment. Self-ratings and observer ratings of mood (visual analog scale 3 times daily and Hamilton Depression Rating Scale) before and after treatment. RESULTS: We found significant interactions of treatment (before and after), response to treatment (Hamilton Depression Rating Scale score <8), and moral valence of the stimuli (positive or negative) in the anterior cingulate cortex, dorsolateral prefrontal cortex, insula, and parietal cortex. In these areas, responders changed their blood oxygen level-dependent responses to emotional stimuli in a pattern opposite of that in nonresponders. Genotype of the promoter for the serotonin transporter predicted response to treatment and influenced baseline neural responses in the anterior cingulate cortex and the dorsolateral prefrontal cortex. CONCLUSION: Multiple factors that affect or are affected at the individual level by major depressive episodes in the course of bipolar disorder significantly interact in influencing brain cortical activity in specific areas. PMID- 17283287 TI - Brain serotonin transporter binding in depressed patients with bipolar disorder using positron emission tomography. AB - CONTEXT: Depression in bipolar disorder is clinically indistinguishable from that observed in major depressive disorder. As in major depression, selective serotonin reuptake inhibitors targeting brain serotonin transporters are first line treatments for bipolar depression. Associations of serotonin transporter promoter polymorphisms and bipolarity have been reported; however, research on alterations in serotonergic neurotransmission in bipolar depression remains scant. OBJECTIVES: To assess in vivo brain serotonin transporter binding potential (BP(1), proportional to serotonin transporter number) in patients with bipolar depression and controls and to examine the relationship between serotonin transporter binding and genotype. DESIGN: Case-control study. SETTING: University hospital. PARTICIPANTS: A sample of 18 medication-free patients with bipolar depression and 41 controls. MAIN OUTCOME MEASURES: In vivo brain serotonin transporter binding was measured using positron emission tomography and radiolabeled trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo [2,1-a]-isoquinoline ([(11)C](+)-McNeil 5652). Participants were genotyped assessing biallelic and triallelic 5-HTTLPR polymorphisms. RESULTS: Patients with bipolar disorder had 16% to 26% lower serotonin transporter BP(1) in the midbrain, amygdala, hippocampus, thalamus, putamen, and anterior cingulate cortex. Triallelic 5-HTTLPR genotypes were unrelated to serotonin transporter BP(1). CONCLUSIONS: Lower serotonin transporter BP(1) in bipolar depression overlaps with that observed in major depression and suggests that serotonergic dysfunction is common to depressive conditions. PMID- 17283288 TI - A genetic family-based association study of OLIG2 in obsessive-compulsive disorder. AB - CONTEXT: Obsessive-compulsive disorder (OCD) is a debilitating familial psychiatric illness with associated brain abnormalities in the white matter. The gene for oligodendrocyte lineage transcription factor 2 (OLIG2) is an essential regulator in the development of cells that produce white matter (myelin). The OLIG2 gene is also highly expressed in brain regions implicated in OCD. OBJECTIVES: To examine OLIG2 as a candidate gene for OCD susceptibility and to explore whether comorbidity subtypes of OCD have distinct associations with OLIG2 and the functionally related OLIG1 gene. It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone. DESIGN: Family-based association candidate gene study. SETTING: Participants and their family members were recruited from tertiary care OCD and TD specialty clinics. PARTICIPANTS: Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD. MAIN OUTCOME MEASURES: Genotypes of single nucleotide polymorphism markers and related haplotypes. RESULTS: The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; P<.001), rs1059004 (minor allele frequency, 44%; P = .005), and rs9653711 (minor allele frequency, 44%; P = .004). A 5-marker haplotype (A/C/T/T/G) constituting these single nucleotide polymorphisms and exonic single nucleotide polymorphisms rs6517137 and rs13046814 was undertransmitted (frequency, 32%; permuted P=.004), whereas the G/A/T/T/C haplotype (frequency, 22%; permuted P=.02) was overtransmitted to probands with OCD alone, with a significant global P value (permuted P=.008). CONCLUSIONS: This is the first study reporting an association between OLIG2 and OCD, specifically when TD comorbidity is absent. The findings support a role for white matter abnormalities in the etiology of the disorder. PMID- 17283289 TI - Association of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention deficit/hyperactivity disorder. AB - CONTEXT: Preclinical studies have demonstrated the relevance of adrenergic alpha2A receptor on the attentional process and the mechanism of action of methylphenidate hydrochloride. Several molecular genetic investigations suggest a role for the adrenergic alpha2A receptor gene (ADRA2A) in attention deficit/hyperactivity disorder (ADHD), especially in the inattentive dimension. However, the effect of ADRA2A in the response to methylphenidate in humans has not been previously investigated, to our knowledge. OBJECTIVE: To evaluate the association between the ADRA2A -1291 C>G polymorphism and the clinical response to methylphenidate treatment in children and adolescents with ADHD. DESIGN: A pharmacogenomic study was undertaken between November 1, 2002, and May 1, 2004, using a nonrandom assignment, quasi-experimental design. SETTING: An ADHD outpatient program at a university hospital in Brazil. Patients One hundred six patients consecutively diagnosed as having ADHD were genotyped for the ADRA2A 1291 C>G polymorphism and were included in the analyses. Intervention Short acting methylphenidate administered in increasing dosages until no further clinical improvement was detected or until limited adverse effects occurred. MAIN OUTCOME MEASURES: The primary outcome measure was the parent-rated inattentive subscale of the Swanson, Nolan, and Pelham Scale version IV. Secondary outcome measures included the Barkley Side Effect Rating Scale and the parent-rated hyperactivity-impulsivity subscale of the Swanson, Nolan, and Pelham Scale version IV. Scales were applied by child psychiatrists blinded to genotype at baseline and at 1 and 3 months of treatment. RESULTS: A significant interaction effect between the presence of the G allele and treatment with methylphenidate over time on inattentive scores was detected during the 3 months of treatment (n = 106; F(2,198) = 4.30; P = .02). CONCLUSIONS: We documented the effect of the G allele at the ADRA2A -1291 C>G polymorphism on the improvement of inattentive symptoms with methylphenidate treatment in children and adolescents with ADHD. Our findings provide clinical evidence for the involvement of the noradrenergic system in the modulation of methylphenidate action. PMID- 17283290 TI - Negative emotions and 3-year progression of subclinical atherosclerosis. AB - CONTEXT: Although depression, anxiety, and hostility/anger have each been associated with an increased risk of coronary artery disease, these overlapping negative emotions have not been simultaneously examined as predictors of the progression of subclinical atherosclerosis. OBJECTIVE: To evaluate the relative importance of depressive symptoms, anxiety symptoms, and hostility/anger in predicting subclinical atherosclerotic progression over a 3-year period. Design/ SETTING: The Pittsburgh Healthy Heart Project, an ongoing prospective cohort study of healthy, older men and women from the general community. At baseline, questionnaires were administered to assess depressive symptoms, anxiety symptoms, hostility, anger experience, and anger expression. Mean carotid intima-media thickness was assessed by B-mode ultrasonography during the baseline and 3-year follow-up visits. PARTICIPANTS: Of the 464 adults enrolled in the project, 324 (69.8%) were included in this report because they had complete baseline and follow-up data. Main Outcome Measure Three-year change in mean carotid intima media thickness. RESULTS: Regression analyses indicated that higher depressive symptoms at baseline were associated with greater 3-year change in carotid intima media thickness (DeltaR(2) = 0.026, P = .002), even after taking into account demographic factors, cardiovascular risk factors, medication use, medical conditions, and other correlated negative emotions. Measures of anxiety symptoms, hostility, anger experience, and anger expression were each unrelated to intima media thickness change. Post hoc analyses examining depressive symptom clusters showed that the somatic-vegetative symptoms of depression (DeltaR(2) = 0.027, P = .002), but not the cognitive-affective symptoms, were positively associated with intima-media thickness change. CONCLUSION: Our findings suggest that the somatic vegetative features of depression, but perhaps not anxiety and hostility/anger, may play an important role in the earlier stages of the development of coronary artery disease. PMID- 17283291 TI - Loneliness and risk of Alzheimer disease. AB - CONTEXT: Social isolation in old age has been associated with risk of developing dementia, but the risk associated with perceived isolation, or loneliness, is not well understood. OBJECTIVE: To test the hypothesis that loneliness is associated with increased risk of Alzheimer disease (AD). DESIGN: Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up. PARTICIPANTS: A total of 823 older persons free of dementia at enrollment were recruited from senior citizen facilities in and around Chicago, Ill. Loneliness was assessed with a 5-item scale at baseline (mean +/- SD, 2.3 +/- 0.6) and annually thereafter. At death, a uniform postmortem examination of the brain was conducted to quantify AD pathology in multiple brain regions and the presence of cerebral infarctions. MAIN OUTCOME MEASURES: Clinical diagnosis of AD and change in previously established composite measures of global cognition and specific cognitive functions. RESULTS: During follow-up, 76 subjects developed clinical AD. Risk of AD was more than doubled in lonely persons (score 3.2, 90th percentile) compared with persons who were not lonely (score 1.4, 10th percentile), and controlling for indicators of social isolation did not affect the finding. Loneliness was associated with lower level of cognition at baseline and with more rapid cognitive decline during follow-up. There was no significant change in loneliness, and mean degree of loneliness during the study was robustly associated with cognitive decline and development of AD. In 90 participants who died and in whom autopsy of the brain was performed, loneliness was unrelated to summary measures of AD pathology or to cerebral infarction. CONCLUSION: Loneliness is associated with an increased risk of late-life dementia but not with its leading causes. PMID- 17283293 TI - Distinguishing vulnerability, prediction, and progression in the preschizophrenic brain. PMID- 17283292 TI - Relative risk of cardiovascular and cancer mortality in people with severe mental illness from the United Kingdom's General Practice Rsearch Database. AB - CONTEXT: People with severe mental illness (SMI) appear to have an elevated risk of death from cardiovascular disease, but results regarding cancer mortality are conflicting. OBJECTIVE: To estimate this excess mortality and the contribution of antipsychotic medication, smoking, and social deprivation. DESIGN: Retrospective cohort study. SETTING: United Kingdom's General Practice Research Database. Patients Two cohorts were compared: people with SMI diagnoses and people without such diagnoses. Main Outcome Measure Mortality rates for coronary heart disease (CHD), stroke, and the 7 most common cancers in the United Kingdom. RESULTS: A total of 46 136 people with SMI and 300 426 without SMI were selected for the study. Hazard ratios (HRs) for CHD mortality in people with SMI compared with controls were 3.22 (95% confidence interval [CI], 1.99-5.21) for people 18 through 49 years old, 1.86 (95% CI, 1.63-2.12) for those 50 through 75 years old, and 1.05 (95% CI, 0.92-1.19) for those older than 75 years. For stroke deaths, the HRs were 2.53 (95% CI, 0.99-6.47) for those younger than 50 years, 1.89 (95% CI, 1.50-2.38) for those 50 through 75 years old, and 1.34 (95% CI, 1.17-1.54) for those older than 75 years. The only significant result for cancer deaths was an unadjusted HR for respiratory tumors of 1.32 (95% CI, 1.04-1.68) for those 50 to 75 years old, which lost statistical significance after controlling for smoking and social deprivation. Increased HRs for CHD mortality occurred irrespective of sex, SMI diagnosis, or prescription of antipsychotic medication during follow-up. However, a higher prescribed dose of antipsychotics predicted greater risk of mortality from CHD and stroke. CONCLUSIONS: This large community sample demonstrates that people with SMI have an increased risk of death from CHD and stroke that is not wholly explained by antipsychotic medication, smoking, or social deprivation scores. Rates of nonrespiratory cancer mortality were not raised. Further research is required concerning prevention of this mortality, including cardiovascular risk assessment, monitoring of antipsychotic medication, and attention to diet and exercise. PMID- 17283294 TI - Amygdala volume status might reflect dominant mode of emotional information processing. PMID- 17283295 TI - An eruption in the neonatal intensive care unit. PMID- 17283296 TI - Results of a general hepatitis C lookback program for persons who received blood transfusions in a neonatal intensive care unit between January 1975 and July 1992. AB - OBJECTIVE: To notify persons who received a blood transfusion in a neonatal intensive care unit between January 1975 and July 1992 of their risk for hepatitis C infection and to encourage them to seek hepatitis C antibody testing. DESIGN: Neonatal intensive care unit, blood bank, and public access records were queried to identify current mailing addresses and persons deceased. All persons were notified by letter. SETTING: Anchorage, Alaska. PARTICIPANTS: Persons who received health care in an integrated health care system, the Alaska Native Medical Center, or in the private sector. Main Exposure Transfusion in the neonatal period. MAIN OUTCOME MEASURES: Prevalence of test results positive for the hepatitis C virus antibody and RNA and awareness of having received a blood transfusion in a neonatal intensive care unit. RESULTS: Alaska Native Medical Center (n = 401) and private sector (n = 1396) persons were targeted for notification. Letters were mailed to 277 Alaska Native Medical Center (69%) and 374 private sector (27%) persons, with 151 (55%) and 65 (17%) screened for hepatitis C, respectively. Among those screened (n = 216), 7 (3%) were hepatitis C antibody positive, with 6 (<3%) also hepatitis C virus-RNA positive. Among 147 persons who responded, 75 (51%) were unaware they had received a transfusion. CONCLUSIONS: Compared with the private sector, a higher proportion of persons were identified and tested from the integrated health care system and more than half of respondents were unaware of their transfusion history. It would be prudent to screen neonatal intensive care unit patients who received transfusions before July 1992 for hepatitis C virus infection. PMID- 17283297 TI - Physical and emotional health of mothers of youth with functional abdominal pain. AB - OBJECTIVE: To determine if mothers of youth with functional abdominal pain (FAP) experience more anxiety, depressive, and somatic symptoms and disorders than mothers of unaffected children. DESIGN: Case-control study. SETTING: Four primary care pediatric practices in western Pennsylvania. PARTICIPANTS: Mothers of 8- to 15-year-old children and adolescents presenting with FAP (59 cases) or for routine care in the absence of recurrent pain (76 controls). OUTCOME MEASURES: Questionnaires and blinded interviews assessing anxiety, depressive, and somatic symptoms and disorders; quality of life; and service use. RESULTS: On univariate analyses, mothers of FAP cases were significantly more likely than mothers of controls to have a lifetime history of irritable bowel syndrome (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.5-10.3), migraine (OR, 2.4; 95% CI, 1.1 5.3), and anxiety (OR, 4.8; 95% CI, 2.2-10.6), depressive (OR, 4.9; 95% CI, 2.2 11.0), and somatoform (OR, 16.1; 95% CI, 2.0-129.8) disorders than mothers of controls, and current anxiety, depressive, and somatic symptoms, poorer overall quality of life, and greater use of ambulatory health, but not mental health, services. Multivariate logistic regression found pediatric FAP to be most closely associated with maternal history of anxiety and depression (adjusted OR, 6.1; 95% CI, 1.8-20.8). CONCLUSIONS: Functional abdominal pain may be better conceptualized as a disorder of emotion than a narrowly defined disorder of gastrointestinal function. Low rates of mental health service use by mothers of youth with FAP suggest that family health and illness attitudes deserve study. PMID- 17283298 TI - Internet prevention messages: targeting the right online behaviors. AB - BACKGROUND: Internet safety programs urge youth to avoid sharing personal information and talking with "strangers" online. OBJECTIVE: To examine whether sharing personal information and talking with strangers online or other behaviors are associated with the greatest odds for online interpersonal victimization. DESIGN: The Second Youth Internet Safety Survey was a cross-sectional random digit-dial telephone survey. SETTING: United States. PARTICIPANTS: A total of 1500 youth aged 10 to 17 years who had used the Internet at least once a month for the previous 6 months. MAIN EXPOSURE: Online behavior, including disclosure of personal information, aggressive behavior, talking with people met online, sexual behavior, and downloading images using file-sharing programs. OUTCOME MEASURE: Online interpersonal victimization (ie, unwanted sexual solicitation or harassment). RESULTS: Aggressive behavior in the form of making rude or nasty comments (adjusted odds ratio [AOR], 2.3; P<.001) or frequently embarrassing others (AOR, 4.6; P = .003), meeting people in multiple ways (AOR, 3.4; P<.001), and talking about sex online with unknown people (AOR, 2.0; P = .02) were significantly related to online interpersonal victimization after adjusting for the total number of different types of online behaviors youth engaged in. Engaging in 4 types of online behaviors seemed to represent a tipping point of increased risk for online interpersonal victimization (OR, 11.3; P<.001). CONCLUSIONS: Talking with people known only online ("strangers") under some conditions is related to online interpersonal victimization, but sharing personal information is not. Engaging in a pattern of different kinds of online risky behaviors is more influential in explaining victimization than many specific behaviors alone. Pediatricians should help parents assess their child's online behaviors globally in addition to focusing on specific types of behaviors. PMID- 17283299 TI - A randomized trial of a multicomponent intervention for adolescent sun protection behaviors. AB - OBJECTIVE: To evaluate a multicomponent primary care-based intervention to increase sun protection behaviors among adolescents. Excessive sun exposure in childhood increases the lifetime risk of melanomas and other forms of skin cancer. Interventions to improve sun protection behaviors in childhood have been based primarily in school and community settings, with little attention to the role of primary care physicians. DESIGN: A 2-year randomized controlled trial. SETTING: Primary care physician offices and participant homes. PARTICIPANTS: Eight hundred nineteen adolescents aged 11 to 15 years. INTERVENTIONS: At the study onset and the 12-month follow-up, the adolescents engaged in an office based expert system assessment of sun protection behaviors followed by brief stage-based counseling from the primary care provider. Participants also received up to 6 expert system-generated feedback reports, a brief printed manual, and periodic mailed tip sheets. Participants randomized to the comparison condition received a physical activity and nutrition intervention. MAIN OUTCOME MEASURE: A self-reported composite measure of sun protection behavior. RESULTS: A random effects repeated-measures model indicated a greater adoption of sun protection behaviors over time in the intervention group compared with the control group. The intervention effect corresponded to between-group differences at 24 months in avoiding the sun and limiting exposure during midday hours and using sunscreen with a sun protection factor of at least 15. Secondary analysis indicated that, by 24 months, more adolescents in the intervention group had moved to the action or the maintenance stage of change than those in the control group (25.1% vs 14.9%; odds ratio, 1.74; 95% confidence interval, 1.13-2.68). Sun protection behavior was also found to be positively associated with the completion of more intervention sessions (P = .002). CONCLUSION: Primary care counseling coupled with a minimal-intensity expert system intervention can improve adolescents' sun protection behaviors. PMID- 17283300 TI - Travel by walking before and after school and physical activity among adolescent girls. AB - OBJECTIVE: To examine how "travel by walking" before and after school contributes to total physical activity of adolescent girls. DESIGN: Cross-sectional sample. SETTING: Thirty-six middle schools from Arizona, Maryland, Minnesota, Louisiana, California, and South Carolina participating in the Trial of Activity for Adolescent Girls (TAAG). PARTICIPANTS: Seventeen hundred twenty-one sixth-grade girls consented to participate; adequate information was available for 1596 participants (93%). MAIN EXPOSURE: Travel by walking before school, after school, and before and after school combined assessed from the 3-Day Physical Activity Recall. MAIN OUTCOME MEASURE: Mean minutes of physical activity measured by accelerometry were estimated for total physical activity (light, moderate, vigorous), moderate to vigorous activity (MVPA), and MVPA of 3 metabolic equivalents. RESULTS: Travel by walking was reported by 14% of participants before school and 18% after school. Girls who reported travel by walking before and after school (combined) had 13.7 more minutes (95% confidence interval, 1.2 26.3) of total physical activity and 4.7 more minutes (95% confidence interval, 2.2-7.2) of MVPA than girls who did not report this activity. Before-school and after-school walkers (but not both) accumulated 2.5 more minutes (95% confidence interval, 0.10-4.9) and 2.2 more minutes (95% confidence interval, 0.24-4.2) of MVPA on an average weekday, respectively, than nonwalkers. CONCLUSION: Our results provide evidence that walking to and from school increases weekday minutes of total physical activity and MVPA for middle-school girls. PMID- 17283301 TI - Serum lipids and glucose control: the SEARCH for Diabetes in Youth study. AB - OBJECTIVE: To assess the relationship of serum lipid concentrations with glucose control in youth with diabetes mellitus. DESIGN: Cross-sectional analyses of data from the SEARCH for Diabetes in Youth study. SETTING: Multicenter study of youth with diabetes onset at younger than 20 years. PATIENTS/ PARTICIPANTS: Nineteen hundred seventy-three SEARCH participants aged 10 years or older with hemoglobin A(1c) and fasting total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride measured at the SEARCH study examination. MAIN EXPOSURE: Hemoglobin A(1c). OUTCOME MEASURE: Lipid concentrations. RESULTS: There were significant trends of higher levels of TC, LDL-C, triglyceride, and non-HDL-C (but not HDL-C) with higher hemoglobin A(1c) concentrations for both diabetes types. The slopes of TC increase were 7.8 mg/dL (0.20 mmol/L) per unit increase in hemoglobin A(1c) for type 1 and 8.1 mg/dL (0.21 mmol/L) for type 2. Levels of TC, LDL-C, triglyceride, and non-HDL-C were all significantly higher (all P values <.001) in type 2 than in type 1 diabetes (mean differences in milligrams per deciliter [millimoles per liter], +13.6 [+0.35] for TC; +8.3 [+0.22] for LDL-C; +66.3 [+0.75] for triglyceride; +25.5 [+0.66] for non-HDL-C). Levels of HDL-C were lower in youth with type 2 diabetes (mean difference, -11.9 mg/dL [-0.31 mmol/L]). Among those with type 1 diabetes in poor glycemic control, 35%, 27%, and 12% had high concentrations of TC (>or=200 mg/dL [5.17 mmol/L]), LDL-C (>or=130 mg/dL [3.36 mmol/L]), and triglyceride (>or=200 mg/dL [2.26 mmol/L]), respectively. In youth with type 2 diabetes in poor glycemic control, percentages with high levels of TC, LDL-C, and triglycerides were 65%, 43%, and 40%, respectively. CONCLUSIONS: Glycemic control and lipid levels are independently associated in youth with both type 1 and type 2 diabetes. PMID- 17283303 TI - Sleep-disordered breathing and blood pressure in children: a meta-analysis. AB - OBJECTIVES: To estimate the risk of elevated blood pressure (BP) in children with obstructive sleep-disordered breathing (SDB) and to explore heterogeneity among published studies. DATA SOURCE: PubMed database. STUDY SELECTION: Pediatric cohort studies that investigated the relationship between SDB and BP. MAIN EXPOSURE: Level of severity of SDB. MAIN OUTCOME MEASURES: Elevated systolic and diastolic BP. RESULTS: During wakefulness, moderate to severe SDB was associated with 87% and 121% higher risk for elevated systolic and diastolic BP, respectively, compared with mild or no SDB, but the association was not statistically significant (random-effects odds ratio [OR], 1.87; 95% confidence interval [CI], 0.73-4.80; and random-effects OR, 2.21; 95% CI, 0.80-6.10, respectively). In terms of heterogeneity, reports of systolic BP were characterized by large heterogeneity (quantification heterogeneity metric [I(2)] = 53%), whereas studies recording diastolic BP had moderate heterogeneity (I(2) = 31%). During sleep, large heterogeneity was identified among studies regarding elevated systolic BP (I(2) = 54%), and the random-effects OR was 1.20 (95% CI, 0.29-5.02). No heterogeneity was detected regarding elevated diastolic BP (I(2) = 0%), although the fixed-effects OR was still not statistically significant (OR, 2.23; 95% CI, 0.61-8.16). CONCLUSIONS: No evidence exists that moderate to severe SDB in childhood increases the risk of elevated BP, and there is heterogeneity among published reports. Large and methodologically rigorous investigations are needed. PMID- 17283302 TI - Cardiovascular fitness is negatively associated with homocysteine levels in female adolescents. AB - OBJECTIVE: To examine the association between cardiovascular fitness and homocysteine levels in adolescents. DESIGN: Cross-sectional study. SETTING: Madrid, Murcia, Granada, Santander, and Zaragoza, Spain. PARTICIPANTS: One hundred fifty-six Spanish adolescents (76 boys and 80 girls) aged (mean +/- SD) 14.8 +/- 1.4 years. MAIN EXPOSURES: Cardiovascular fitness was measured by the 20 m shuttle run test. Pubertal stage, birth weight, smoking status, and socioeconomic status were determined, and the sum of 6 skinfold thickness measurements, and serum folic acid and vitamin B(12) levels were measured. Methylenetetrahydrofolate reductase (MTHFR; 677C>T genotype) polymorphism was done by DNA sequencing. MAIN OUTCOME MEASURE: Fasting homocysteine levels. RESULTS: Mean values of homocysteine were significantly higher in the MTHFR 677CT and TT genotype subgroups compared with the CC genotype subgroup in adolescent boys, whereas in adolescent girls, mean values of homocysteine were significantly higher in the MTHFR 677CT and TT genotype subgroup compared with the CC and CT genotype subgroups. Multiple regression analyses showed that cardiovascular fitness was significantly associated with homocysteine levels in female adolescents after controlling for potential confounders including the MTHFR 677C>T genotype (beta = -0.40; semipartial correlation = -0.35; P = .007). No associations were found between cardiovascular fitness and homocysteine levels in male adolescents (beta = 0.12; semipartial correlation = 0.08; P = .51). CONCLUSION: The results suggest that cardiovascular fitness is negatively associated with homocysteine levels in female adolescents after controlling for potential cofounders including MTHFR 677C>T genotype. PMID- 17283304 TI - Reporting and disclosing medical errors: pediatricians' attitudes and behaviors. AB - OBJECTIVE: To characterize pediatricians' attitudes and experiences regarding communicating about errors with the hospital and patients' families. DESIGN: Cross-sectional survey. SETTING: St Louis, Mo, and Seattle, Wash. PARTICIPANTS: University-affiliated hospital and community pediatricians and pediatric residents. MAIN EXPOSURE: Anonymous 68-item survey (paper or Web-based) administered between July 2003 and March 2004. MAIN OUTCOME MEASURES: Physician attitudes and experiences about error communication. RESULTS: Four hundred thirty nine pediatric attending physicians and 118 residents participated (62% response rate). Most respondents had been involved in an error (39%, serious; 72%, minor; 61%, near miss; 7%, none). Respondents endorsed reporting errors to the hospital (97%, serious; 90%, minor; 82%, near miss), but only 39% thought that current error reporting systems were adequate. Most pediatricians had used a formal error reporting mechanism, such as an incident report (65%), but many also used informal reporting mechanisms, such as telling a supervisor (47%) or senior physician (38%), and discussed errors with colleagues (72%). Respondents endorsed disclosing errors to patients' families (99%, serious; 90%, minor; 39%, near miss), and many had done so (36%, serious; 52%, minor). Residents were more likely than attending physicians to believe that disclosing a serious error would be difficult (96% vs 86%; P = .004) and to want disclosure training (69% vs 56%; P = .03). CONCLUSIONS: Pediatricians are willing to report errors to hospitals and disclose errors to patients' families but believe current reporting systems are inadequate and struggle with error disclosure. Improving error reporting systems and encouraging physicians to report near misses, as well as providing training in error disclosure, could help prevent future errors and increase patient trust. PMID- 17283306 TI - Time trends in reported diagnoses of childhood neuropsychiatric disorders: a Danish cohort study. AB - OBJECTIVES: To examine trends in autism (autism spectrum disorder and childhood autism) in the context of 3 additional childhood neuropsychiatric disorders: hyperkinetic disorder, Tourette syndrome, and obsessive-compulsive disorder. DESIGN: Population-based cohort study. SETTING: Children were identified in the Danish Medical Birth Registry. Relevant outcomes were obtained via linkage with the Danish National Psychiatric Register, which included reported diagnoses through 2004 by psychiatrists using diagnostic criteria from the International Statistical Classification of Diseases, 10th Revision. PARTICIPANTS: All children born in Denmark from 1990 through 1999, a total of 669 995 children. MAIN OUTCOME MEASURES: Cumulative incidence proportion by age, stratified by year of birth, for each disorder. RESULTS: Statistically significant increases were found in cumulative incidence across specific birth years for autism spectrum disorder, childhood autism, hyperkinetic disorder, and Tourette syndrome. No significant change in cumulative incidence was observed for obsessive-compulsive disorder. CONCLUSIONS: Recent increases in reported autism diagnoses might not be unique among childhood neuropsychiatric disorders and might be part of a more widespread epidemiologic phenomenon. The reasons for the observed common pattern of change in reported cumulative incidence could not be determined in this study, but the data underscore the growing awareness of and demand for services for children with neurodevelopmental disorders in general. PMID- 17283307 TI - Picture of the month. Acquired secondary syphilis. PMID- 17283305 TI - Conjoined effects of low birth weight and childhood abuse on adaptation and well being in adolescence and adulthood. AB - OBJECTIVE: To characterize the conjoined effects of low birth weight (LBW) and childhood abuse on impaired adaptation and illness in adolescence and adulthood. DESIGN: Longitudinal study of a birth cohort. SETTING: Baltimore, Md. PARTICIPANTS: Children (N = 1748) were followed from birth to adulthood (mean age, 26 years) as part of the Johns Hopkins Collaborative Perinatal Study. MAIN EXPOSURES: Childhood abuse and LBW. MAIN OUTCOME MEASURES: Indicators of adaptation were delinquency, school suspension, repeating grades, academic honors, quality of life, and socioeconomic status. Indicators of psychiatric and medical problems were depression, social dysfunction, somatization, asthma, and hypertension. RESULTS: Participants with both LBW and subsequent childhood abuse, relative to those with neither risk, were at a substantially elevated risk for psychological problems: 10-fold for depression; nearly 9-fold for social dysfunction, and more than 4-fold for somatization. However, they were not at an elevated risk for medical problems in adulthood. Those exposed to childhood abuse were more likely to report delinquency, school suspension, repeating grades during adolescence, and impaired well-being in adulthood, regardless of LBW status. For those with LBW alone, the prevalence of those problems was comparable with that of individuals without either risk factor. CONCLUSIONS: Children with LBW and childhood abuse are at much greater risk for poor adaptation and psychiatric problems than those with LBW alone and those with neither risk. Preventive interventions should target families with LBW children who are at greater risk for childhood abuse. PMID- 17283309 TI - What to do about the new and growing digital divide? PMID- 17283308 TI - Finding adolescents and young adults with transfusion-associated hepatitis C: looking forward to looking back. PMID- 17283310 TI - Determining future stroke risk using MRI: new data, new questions. PMID- 17283311 TI - Rehabilitating mental representations: a genuinely "blind" study. PMID- 17283312 TI - Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. AB - OBJECTIVE: We report the results of a prospective study of the efficacy and tolerability of levetiracetam, a new antiepileptic drug with a unique mechanism of action, in comparison with controlled-release carbamazepine as first treatment in newly diagnosed epilepsy. METHODS: Adults with > or =2 partial or generalized tonic-clonic seizures in the previous year were randomly assigned to levetiracetam (500 mg twice daily, n = 288) or controlled-release carbamazepine (200 mg twice daily, n = 291) in a multicenter, double-blind, noninferiority, parallel-group trial. If a seizure occurred within 26 weeks of stabilization, dosage was increased incrementally to a maximum of levetiracetam 1,500 mg twice daily or carbamazepine 600 mg twice daily. Patients achieving the primary endpoint (6-month seizure freedom) continued on treatment for a further 6-month maintenance period. RESULTS: At per-protocol analysis, 73.0% (56.6%) of patients randomized to levetiracetam and 72.8% (58.5%) receiving controlled-release carbamazepine were seizure free at the last evaluated dose (adjusted absolute difference 0.2%, 95% CI -7.8% to 8.2%) for > or =6 months (1 year). Of all patients achieving 6-month (1-year) remission, 80.1% (86.0%) in the levetiracetam group and 85.4% (89.3%) in the carbamazepine group did so at the lowest dose level. Withdrawal rates for adverse events were 14.4% with levetiracetam and 19.2% with carbamazepine. CONCLUSIONS: Levetiracetam and controlled-release carbamazepine produced equivalent seizure freedom rates in newly diagnosed epilepsy at optimal dosing in a setting mimicking clinical practice. This trial has confirmed in a randomized, double-blind setting previously uncontrolled observations that most people with epilepsy will respond to their first-ever antiepileptic drug at low dosage. PMID- 17283313 TI - ApoE-epsilon4 is associated with reduced memory in long-standing intractable temporal lobe epilepsy. AB - OBJECTIVE: To investigate the relationship between the apolipoprotein (ApoE) epsilon4 allele and memory performance (verbal and nonverbal) in patients with medically intractable temporal lobe epilepsy (TLE) who underwent temporal lobectomy. METHODS: Presurgical and postsurgical memory performance was examined in 87 adult patients with TLE (epsilon4 = 22; non-epsilon4 = 65) to determine whether the expression of ApoE-epsilon4 may be associated with memory performance in this population and to examine how this relationship may be affected by duration of epilepsy. RESULTS: There was a significant interaction between ApoE epsilon4 status and duration of epilepsy such that epsilon4 carriers with a long duration of epilepsy demonstrated the poorest memory performance on both verbal and nonverbal measures. This relationship was observed both before and after temporal lobectomy, with little change in test performance over time. CONCLUSIONS: The ApoE-epsilon4 allele interacts with longstanding seizures to affect memory performance, both verbal and nonverbal, in patients with medically intractable temporal lobe epilepsy. PMID- 17283314 TI - Acute parkinsonism with corresponding lesions in the basal ganglia after heroin abuse. PMID- 17283316 TI - Comparison of elective stenting of severe vs moderate intracranial atherosclerotic stenosis. AB - OBJECTIVE: To test whether symptomatic severe intracranial atherosclerotic stenosis was associated with a higher subsequent stroke risk than moderate stenosis after elective angioplasty with a balloon-expandable stent and to explore which factors were associated with the subsequent stroke. METHODS: Between September 2001 and June 2005, there were 220 symptomatic intracranial atherosclerotic stenoses in 213 patients undergoing elective stenting at our institute. Of these stenoses, 126 in 121 patients were > or =70% severe stenoses, and 94 in 92 patients were 50% to 69% moderate stenoses. Primary endpoints included lesion-related ischemic stroke, and symptomatic brain or subarachnoid hemorrhage. RESULTS: Ten primary endpoint events occurred in the severe stenosis group (six within 30 days and four in mean follow-up of 26.0 months after 30 days), and seven occurred in the moderate stenosis group (four within 30 days and three in mean follow-up of 27.6 months after 30 days). There was no significant difference in cumulative probability of primary endpoints between the severe (7.2% at 1 year and 8.2% at 2 years) and moderate (5.3% at 1 year and 8.3% at 2 years) stenosis groups. No single factor was found to be associated with primary endpoints in the moderate stenosis group. Multivariable analysis revealed that stent failure was the only predictor of primary endpoints in the severe stenosis group (hazard ratio 5.31, 95% CI 1.35 to 20.91). CONCLUSION: Symptomatic severe intracranial atherosclerotic stenosis did not present a higher subsequent stroke risk than moderate stenosis after elective angioplasty with a balloon-expandable stent. Patients with severe stenosis may benefit from successful stent placement, and randomized trials are necessary to demonstrate this possible benefit. PMID- 17283315 TI - Acute ischemic lesions of varying ages predict risk of ischemic events in stroke/TIA patients. AB - BACKGROUND: Multiple ischemic lesions identified by diffusion-weighted imaging (DWI) have been shown to predict high risk of future ischemic events. However, the importance of lesion age has not been factored into this risk. Our goal was to evaluate whether the presence of ischemic lesions of varying ages identified by DWI and apparent diffusion coefficient (ADC) suggests a higher risk of future ischemic events. METHODS: Patients with acute stroke and TIA presenting within 12 hours of symptom onset who had a baseline and 1-month follow-up MRI were enrolled in the study. Acute ischemic lesions were divided into DWI positive with ADC low lesions and DWI positive with ADC normalized lesions. The baseline MRI and the presence of new lesions on the follow-up MRI were analyzed. RESULTS: A total of 360 patients were prospectively enrolled, and all had appropriate imaging. Two hundred twenty-three were excluded as there were no DWI lesions, they received recombinant tissue plasminogen activator, or they did not have the 30-day follow up MRI. One hundred seventeen patients had DWI lesions of one age (DWI positive with either ADC low lesions or ADC normalized lesions alone) and 20 had lesions of varying ages (DWI positive lesions with reduced and normalized ADC) on the baseline MRI. Patients with multiple DWI lesions of varying ages were at more risk of having new lesions on the 30-day MRI compared with those having lesions of the same age (relative risk = 3.6; 95% CI 1.9 to 6.8). Multiple DWI lesions of varying ages (odds ratio [OR] 6.6; 95% CI 2.3 to 19.1) and cardioembolic stroke subtype (OR 3.2; 95% CI 1.1 to 8.7) were independently associated with new lesion recurrence by multiple logistic regression analysis. CONCLUSION: The presence of multiple diffusion-weighted imaging lesions of varying ages suggests very active early recurrence over time and portends a higher early risk of future ischemic events. PMID- 17283317 TI - Lack of aggregation of ischemic stroke subtypes within affected sibling pairs. AB - OBJECTIVE: To establish whether subtypes of ischemic stroke aggregate within ischemic stroke-affected sibling pairs more than expected by chance alone. METHODS: This retrospective family study was based on a pooled analysis of two cohorts of male and female adult sibling pairs with symptomatic ischemic stroke. One hospital-based cohort of 404 individuals (first proband seen August 30, 1999) was recruited from the United States and Canada, and another population-based cohort of 198 individuals (first proband seen April 17, 1997) was recruited from Umea, Sweden. Subtype diagnoses were based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Agreement for subtype diagnoses within families was poor (mean +/- asymptotic SE kappa = 0.17 +/- 0.04). Occurrence of one ischemic stroke subtype in a proband was not associated with a greater likelihood of that subtype being the qualifying stroke subtype in the sibling. Comparable levels of agreement were seen when restricting the analysis to same sex sibling pairs (kappa = 0.22 +/- 0.05) to sibling pairs in which the proband's stroke occurred before the age of 65 years (kappa = 0.16 +/- 0.05) or to pairs in which the proband's stroke occurred at or after the age of 65 years (kappa = 0.19 +/- 0.05). CONCLUSIONS: The subtype of ischemic stroke in a proband was a poor determinant of the subtype of ischemic stroke in the respective sibling. This suggests that many genetic risk factors for ischemic stroke may not be specific for one subtype. PMID- 17283318 TI - Looking while imagining: the influence of visual input on representational neglect. AB - BACKGROUND: Subjects with hemispatial neglect often exhibit representational neglect: a failure to report details from the left side of mentally visualized images. This failure could reflect impaired ability to generate the left side of the mental image, or it could reflect failure to explore the left side of a normally generated mental image. When subjects with hemispatial neglect look at pictures or drawings, their attention tends to be drawn to objects on the right side, thereby aggravating their failure to explore the left side. If representational neglect represents a failure to explore the left side of a normally generated mental visual image, then it should be improved by blindfolding, which removes the attention-catching right-sided stimuli. However, if representational neglect represents a failure to generate the left side of the mental visual image, then blindfolding should have little impact on reporting of details of the image. METHODS: To determine which of these explanations is correct, we asked eight normal participants and eight brain-damaged patients with left representational neglect to imagine the map of France and to name as many towns as possible in 2 minutes. In different sessions, participants performed the task with eyes open or while blindfolded. RESULTS: Normal participants mentioned more towns while blindfolded than with vision, thus suggesting a distracting effect of visual details on mental imagery. Patients with neglect, however, showed no appreciable effect of blindfolding on reporting of details from either side of mental images. CONCLUSION: Representational neglect may represent a failure to generate the left side of mental images. PMID- 17283319 TI - Pathologic startle following brainstem lesion. PMID- 17283320 TI - Infantile spasm-associated microencephaly in tuberous sclerosis complex and cortical dysplasia. AB - OBJECTIVE: In children with and without infantile spasms, this study determined brain volumes and cell densities in epilepsy surgery patients with tuberous sclerosis complex (TSC) and cortical dysplasia with balloon cells (CD). METHODS: We compared TSC (n = 18) and CD (n = 17) patients with normal/autopsy controls (n = 20) for MRI gray and white matter volumes and neuronal nuclei (NeuN) cell densities. RESULTS: In patients without a history of infantile spasms, TSC cases showed decreased gray and white matter volumes (-16%). In cases with a history of infantile spasms, both CD (-25%) and TSC (-35%) patients showed microencephaly. This was confirmed in monozygotic twins with TSC, where the twin with a history of spasms had cerebral volumes less (-16%) than the twin without a history of seizures. Regardless of seizure history, TSC patients showed decreased NeuN cell densities in lower gray matter (-36%), whereas CD patients had increased densities in upper cortical (+52%) and white matter regions (+65%). For TSC patients, decreased lower gray matter NeuN densities correlated with reduced MRI volumes. CONCLUSIONS: Patients with tuberous sclerosis without spasms showed microencephaly associated with decreased cortical neuronal densities. In contrast, cortical dysplasia patients without spasms were normocephalic with increased cell densities. This supports the concept that tuberous sclerosis and cortical dysplasia have different pathogenetic mechanisms despite similarities in refractory epilepsy and postnatal histopathology. Furthermore, a history of infantile spasms was associated with reduced cerebral volumes in both cortical dysplasia and tuberous sclerosis patients, suggesting that spasms or their treatment may contribute to microencephaly independent of etiology. PMID- 17283323 TI - Long-term outcome of bilateral pallidal deep brain stimulation for primary cervical dystonia. AB - Ten patients with severe cervical dystonia (CD) unresponsive to medical treatment underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed for 31.9 +/- 20.9 months. At last follow-up, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity score improved by 54.8%, the TWSTRS disability score improved by 59.1%, and the TWSTRS pain score improved by 50.4%. Bilateral GPi DBS is an effective long-term therapy in patients with CD. PMID- 17283322 TI - Preclinical validation of a multiplex real-time assay to quantify SMN mRNA in patients with SMA. AB - OBJECTIVE: To determine whether survival motor neuron (SMN) expression was stable over time. METHODS: We developed a multiplex real-time reverse transcriptase (RT) PCR assay to quantify SMN transcripts in preclinical blood samples from 42 patients with spinal muscular atrophy (SMA) drawn for three time points per patient; most blood samples were shipped to a centralized laboratory. RESULTS: We obtained a sufficient amount (9.7 +/- 5.6 microg) of good-quality total RNA, and RNAs were stable for up to a 3-year interval. This allowed RNA samples collected during a 9- to 12-month period to be analyzed in a single run, thus minimizing interexperimental variability. SMN expression was stable over time; intersample variability for baseline measures, collected during a 17-month interval, was less than 15% for 38 of 42 SMA patients analyzed. This variability was well below the 1.95-fold increase in full-length SMN (flSMN) transcripts detected in SMA fibroblasts treated with 10 mM valproic acid. CONCLUSION: Real-time quantification of SMN messenger RNA expression may be a biomarker that is amenable to multicenter SMA clinical trials. PMID- 17283321 TI - Multiplex ligation-dependent probe amplification detects DCX gene deletions in band heterotopia. AB - BACKGROUND: Subcortical band heterotopia (SBH, or double cortex syndrome) is a neuronal migration disorder consisting of heterotopic bands of gray matter located between the cortex and the ventricular surface, with or without concomitant pachygyria. Most cases show diffuse or anteriorly predominant (A>P) migration abnormality. All familial and 53% to 84% of sporadic cases with diffuse or A>P SBH harbor a mutation of the DCX gene, leaving the genetic causes unexplained, and genetic counseling problematic, in the remaining patients. Our purpose was to verify the extent to which exonic deletions or duplications of the DCX gene would account for sporadic SBH with A>P gradient but normal gene sequencing. METHODS: We identified 23 patients (22 women, 1 man) with sporadic, diffuse, or anteriorly predominant SBH. After sequencing the DCX gene and finding mutations in 12 (11 women, 1 man), we used multiplex ligation-dependent probe amplification (MLPA) to search for whole-exon deletions or duplications in the 11 remaining women. We used semiquantitative fluorescent multiplex PCR (SQF-PCR) and Southern blot to confirm MLPA findings. RESULTS: MLPA assay uncovered two deletions encompassing exons 3 to 5, and one involving exon 6, in 3 of 11 women (27%) and raised the percentage of DCX mutations from 52% to 65% in our series. SQF-PCR performed in all three women and Southern blot analysis performed in two confirmed the deletions. CONCLUSIONS: MLPA uncovers large genomic deletions of the DCX gene in a subset of patients with SBH in whom no mutations are found after gene sequencing. Deletions of DCX are an underascertained cause of SBH. PMID- 17283324 TI - An 85-year-old man with chronic lymphocytic leukemia and altered mental status. PMID- 17283325 TI - Severe recurrent myelitis in patients with hepatitis C virus infection. PMID- 17283326 TI - Stroke care delivery before vs after JCAHO stroke center certification. PMID- 17283327 TI - Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. PMID- 17283328 TI - Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers. PMID- 17283329 TI - Oxcarbazepine adjunctive therapy in infants and young children with partial seizures. PMID- 17283330 TI - Virstatin inhibits dimerization of the transcriptional activator ToxT. AB - The development of antimicrobials is critical in this time of increasing antibiotic resistance of most clinically relevant bacteria. To date, all current antibiotics focus on inhibiting crucial enzymatic activities of their protein targets (i.e., trimethoprim for dihydrofolate reductase), thus disrupting in vitro essential gene functions. In contrast, we have previously reported the identification of virstatin, a small molecule that inhibits virulence regulation in Vibrio cholerae, thereby preventing intestinal colonization in an infant mouse model for cholera. Virstatin prevents expression of the two major V. cholerae virulence factors, cholera toxin (CT) and the toxin coregulated pilus, by inhibiting the virulence transcriptional activator ToxT. It has previously been described that the N-terminal domain of ToxT has the ability to form homodimers. We now demonstrate that virstatin inhibits ToxT dimerization, thus demonstrating that it further falls into a unique class of inhibitors that works by disrupting protein-protein interactions, particularly homodimerization. Using virstatin, truncation mutants of ToxT, and a virstatin-resistant mutant, we show that dimerization is required for ToxT activation of the ctx promoter. In contrast, ToxT dimerization does not appear to be required at all of the other ToxT regulated promoters, suggesting multiple mechanisms may exist for its transcriptional activity. PMID- 17283331 TI - Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1. AB - Accumulating evidence has shown that many molecules, including some cyclin dependent kinases (Cdks) and cyclins, as well as the death-effector domain (DED) containing FADD, function for both apoptosis and cell cycle. Here we identified that DEDD, which also possesses the DED domain, acts as a novel inhibitor of the mitotic Cdk1/cyclin B1 complex. DEDD associates with mitotic Cdk1/cyclin B1 complexes via direct binding to cyclin B1 and reduces their function. In agreement, kinase activity of nuclear Cdk1/cyclin B1 in DEDD-null (DEDD-/-) embryonic fibroblasts is increased compared with that in DEDD+/+ cells, which results in accelerated mitotic progression, thus exhibiting a shortened G2/M stage. Interestingly, DEDD-/- cells also demonstrated decreased G1 duration, which perhaps enhanced the overall reduction in rRNA amounts and cell volume, primarily caused by the rapid termination of rRNA synthesis before cell division. Likewise, DEDD-/- mice show decreased body and organ weights relative to DEDD+/+ mice. Thus, DEDD is an impeder of cell mitosis, and its absence critically influences cell and body size via modulation of rRNA synthesis. PMID- 17283332 TI - Discovery of growth hormone-releasing hormones and receptors in nonmammalian vertebrates. AB - In mammals, growth hormone-releasing hormone (GHRH) is the most important neuroendocrine factor that stimulates the release of growth hormone (GH) from the anterior pituitary. In nonmammalian vertebrates, however, the previously named GHRH-like peptides were unable to demonstrate robust GH-releasing activities. In this article, we provide evidence that these GHRH-like peptides are homologues of mammalian PACAP-related peptides (PRP). Instead, GHRH peptides encoded in cDNAs isolated from goldfish, zebrafish, and African clawed frog were identified. Moreover, receptors specific for these GHRHs were characterized from goldfish and zebrafish. These GHRHs and GHRH receptors (GHRH-Rs) are phylogenetically and structurally more similar to their mammalian counterparts than the previously named GHRH-like peptides and GHRH-like receptors. Information regarding their chromosomal locations and organization of neighboring genes confirmed that they share the same origins as the mammalian genes. Functionally, the goldfish GHRH dose-dependently activates cAMP production in receptor-transfected CHO cells as well as GH release from goldfish pituitary cells. Tissue distribution studies showed that the goldfish GHRH is expressed almost exclusively in the brain, whereas the goldfish GHRH-R is actively expressed in brain and pituitary. Taken together, these results provide evidence for a previously uncharacterized GHRH GHRH-R axis in nonmammalian vertebrates. Based on these data, a comprehensive evolutionary scheme for GHRH, PRP-PACAP, and PHI-VIP genes in relation to three rounds of genome duplication early on in vertebrate evolution is proposed. These GHRHs, also found in flounder, Fugu, medaka, stickleback, Tetraodon, and rainbow trout, provide research directions regarding the neuroendocrine control of growth in vertebrates. PMID- 17283333 TI - Targeted cell killing by reconstituted caspases. AB - We have developed a two-component system involving reconstituted caspase (recCaspase) for selective and/or conditional ablation of targeted cells. Caspases, the executioners of programmed cell death, are normally synthesized as inactive zymogens and are activated by proteolytic processing of their subunits. We show here, using two different caspases, Caenorhabditis elegans CED-3 and human Caspase-3, that coexpression of the subunits generates constitutively active caspase activity that leads to cell death. This recCaspase activity, however, occurred only when the subunits associated through binding of linked antiparallel leucine-zipper domains. We exploited the dual-component nature of recCaspases by expressing the individual subunits from combinations of promoters either to target selectively the subset of cells for apoptosis or induce cell death in specific cells at specific times during development. The high degree of target specificity and tight regulation of induction of recCaspase would be advantageous in creating animal models that are ablated for specific cells and in other targeted cell killings. PMID- 17283334 TI - Identification of prostate cancer mRNA markers by averaged differential expression and their detection in biopsies, blood, and urine. AB - The advent of serum prostate-specific antigen (PSA) as a biomarker has enabled early detection of prostate cancer and, hence, improved clinical outcome. However, a low PSA is not a guarantee of disease-free status, and an elevated PSA is frequently associated with a negative biopsy. Therefore, our goal is to identify molecular markers that can detect prostate cancer with greater specificity in body fluids such as urine or blood. We used the RT-PCR differential display method to first identify mRNA transcripts differentially expressed in tumor vs. patient-matched nontumor prostate tissue. This analysis led to the identification of 44 mRNA transcripts that were expressed differentially in some but not all tumor specimens examined. To identify mRNA transcripts that are differentially expressed in most tumor specimens, we turned to differential display of pooled tissue samples, a technique we name averaged differential expression (ADE). We performed differential display of mRNA from patient-matched nontumor vs. tumor tissue, each pooled from 10 patients with various Gleason scores. Differentially expressed mRNA transcripts identified by ADE were fewer in number, but were expressed in a greater percentage of tumors (>75%) than those identified by differential display of mRNA from individual patient samples. Differential expression of these mRNA transcripts was also detected by RT-PCR in mRNA isolated from urine and blood samples of prostate cancer patients. Our findings demonstrate the principle that specific cDNA probes of frequently differentially expressed mRNA transcripts identified by ADE can be used for the detection of prostate cancer in urine and blood samples. PMID- 17283335 TI - A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse. AB - The neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for synaptic vesicle exocytosis, but its study has been limited by the neonatal lethality of murine SNARE knockouts. Here, we describe a viable mouse line carrying a mutation in the b-isoform of neuronal SNARE synaptosomal-associated protein of 25 kDa (SNAP-25). The causative I67T missense mutation results in increased binding affinities within the SNARE complex, impaired exocytotic vesicle recycling and granule exocytosis in pancreatic beta-cells, and a reduction in the amplitude of evoked cortical excitatory postsynaptic potentials. The mice also display ataxia and impaired sensorimotor gating, a phenotype which has been associated with psychiatric disorders in humans. These studies therefore provide insights into the role of the SNARE complex in both diabetes and psychiatric disease. PMID- 17283336 TI - The 3D structure of a periplasm-spanning platform required for assembly of group 1 capsular polysaccharides in Escherichia coli. AB - Capsular polysaccharides (CPSs) are essential virulence determinants of many pathogenic bacteria. Escherichia coli group 1 CPSs provide paradigms for widespread surface polysaccharide assembly systems in Gram-negative bacteria. In these systems, complex carbohydrate polymers must be exported across the periplasm and outer membrane to the cell surface. Group 1 CPS export requires oligomers of the outer membrane protein, Wza, for translocation across the outer membrane. Assembly also depends on Wzc, an inner membrane tyrosine autokinase known to regulate export and synthesis of group 1 CPS. Here, we provide a structural view of a complex comprising Wzc and Wza that spans the periplasm, connecting the inner and outer membranes. Examination of transmembrane sections of the complex suggests that the periplasm is compressed at the site of complex formation. An important feature of CPS production is the coupling of steps involved in biosynthesis and export. We propose that the Wza-Wzc complex provides the structural and regulatory core of a larger macromolecular machine. We suggest a mechanism by which CPS may move from the periplasm through the outer membrane. PMID- 17283337 TI - Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6. AB - Fetal loss in animals and humans is frequently associated with inflammatory conditions. D6 is a promiscuous chemokine receptor with decoy function, expressed in lymphatic endothelium, that recognizes and targets to degradation most inflammatory CC chemokines. Here, we report that D6 is expressed in placenta on invading extravillous trophoblasts and on the apical side of syncytiotrophoblast cells, at the very interface between maternal blood and fetus. Exposure of D6-/- pregnant mice to LPS or antiphospholipid autoantibodies results in higher levels of inflammatory CC chemokines and increased leukocyte infiltrate in placenta, causing an increased rate of fetal loss, which is prevented by blocking inflammatory chemokines. Thus, the promiscuous decoy receptor for inflammatory CC chemokines D6 plays a nonredundant role in the protection against fetal loss caused by systemic inflammation and antiphospholipid antibodies. PMID- 17283338 TI - X-ray fluorescence microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis. AB - Although copper has been reported to influence numerous proteins known to be important for angiogenesis, the enhanced sensitivity of this developmental process to copper bioavailability has remained an enigma, because copper metalloproteins are prevalent and essential throughout all cells. Recent developments in x-ray optics at third-generation synchrotron sources have provided a resource for highly sensitive visualization and quantitation of metalloproteins in biological samples. Here, we report the application of x-ray fluorescence microscopy (XFM) toin vitro models of angiogenesis and neurogenesis, revealing a surprisingly dramatic spatial relocalization specific to capillary formation of 80-90% of endogenous cellular copper stores from intracellular compartments to the tips of nascent endothelial cell filopodia and across the cell membrane. Although copper chelation had no effect on process formation, an almost complete ablation of network formation was observed. XFM of highly vascularized ductal carcinomas showed copper clustering in putative neoangiogenic areas. This use of XFM for the study of a dynamic developmental process not only sheds light on the copper requirement for endothelial tube formation but highlights the value of synchrotron-based facilities in biological research. PMID- 17283339 TI - Vaccinia virus D10 protein has mRNA decapping activity, providing a mechanism for control of host and viral gene expression. AB - Previous studies indicated that the vaccinia virus D10 protein, which is conserved in all sequenced poxviruses, participates in the rapid turnover of host and viral mRNAs. D10 contains a motif present in the family of Nudix/MutT enzymes, a subset of which has been shown to enhance mRNA turnover in eukaryotic cells through cleavage of the 5' cap (m7GpppNm-). Here, we demonstrate that a purified recombinant D10 fusion protein possesses an intrinsic activity that liberates m7GDP from capped RNA substrates. Furthermore, point mutations in the Nudix/MutT motif abolished decapping activity. D10 has a strong affinity for capped RNA substrates (Km approximately 3 nm). RNAs of 24-309 nt were decapped to comparable extents, whereas the cap of a 12-nt RNA was uncleaved. At large molar ratios relative to capped RNA substrate, competitor m7GpppG, m7GTP, or m7GDP inhibited decapping, whereas even higher concentrations of unmethylated analogs did not. High concentrations of uncapped RNA were also inhibitory, suggesting that D10 recognizes its substrate through interaction with both cap and RNA moieties. Thus far, poxviruses represent the only virus family shown to encode a Nudix hydrolase-decapping enzyme. Although it may seem self-destructive for a virus to encode a decapping and a capping enzyme, accelerated mRNA turnover helps eliminate competing host mRNAs and allows stage-specific synthesis of viral proteins. PMID- 17283340 TI - Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain. AB - Aminoacyl-tRNA synthetases are multidomain proteins responsible for the attachment of specific amino acids to their tRNA substrates. Prolyl-tRNA synthetases (ProRSs) are notable due to their particularly diverse architectures through evolution. For example, Saccharomyces cerevisiae ProRS possesses an N terminal extension with weak homology to a bacterial-specific domain typically present as an insertion (INS) within the aminoacylation active site. The INS domain has been shown to contain a "posttransfer" editing active site responsible for cleaving the aminoacyl-ester bond of misacylated Ala-tRNA(Pro) species. However, wild-type S. cerevisiae ProRS does not perform posttransfer editing in vitro. Here, we show that replacement of the N-terminal domain of S. cerevisiae ProRS with the Escherichia coli INS domain confers posttransfer editing function to this chimeric enzyme, with specificity for yeast Ala-tRNA(Pro). In contrast, the isolated INS domain displays only weak editing activity and lacks tRNA sequence specificity. These results emphasize the modular nature of synthetase editing active sites and demonstrate how in evolution, a weak editing activity can be converted to a more robust state through fusion to the body of a synthetase. In this manner, a single editing module can be distributed to different synthetases, and simultaneously acquire specificity and enhanced activity. PMID- 17283341 TI - Disulfide formation as a probe of folding in GroEL-GroES reveals correct formation of long-range bonds and editing of incorrect short-range ones. AB - The chaperonin GroEL assists protein folding by binding nonnative forms through exposed hydrophobic surfaces in an open ring and mediating productive folding in an encapsulated hydrophilic chamber formed when it binds GroES. Little is known about the topology of nonnative proteins during folding inside the GroEL-GroES cis chamber. Here, we have monitored topology employing disulfide bond formation of a secretory protein, trypsinogen (TG), that behaves in vitro as a stringent, GroEL-GroES-requiring substrate. Inside the long-lived cis chamber formed by SR1, a single-ring version of GroEL, complexed with GroES, we observed an ordered formation of disulfide bonds. First, short-range disulfides relative to the primary structure formed, both native and nonnative. Next, the two long-range native disulfides that "pin" the two beta-barrel domains together formed. Notably, no long-range nonnative bonds were ever observed, suggesting that a native-like long-range topology is favored. At both this time and later, however, the formation of several medium-range nonnative bonds mapping to one of the beta barrels was observed, reflecting that the population of local nonnative structure can occur even within the cis cavity. Yet both these and the short-range nonnative bonds were ultimately "edited" to native, as evidenced by the nearly complete recovery of native TG. We conclude that folding in the GroEL-GroES cavity can favor the formation of a native-like topology, here involving the proper apposition of the two domains of TG; but it also involves an ATP independent conformational "editing" of locally incorrect structures produced during the dwell time in the cis cavity. PMID- 17283343 TI - Summaries for patients. A brief intervention for hospitalized patients with unhealthy alcohol use. PMID- 17283342 TI - Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice. AB - C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1 positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a beta3-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice. PMID- 17283344 TI - Summaries for patients. Safety of surgery during bridging anticoagulation therapy with low-molecular-weight heparin. PMID- 17283345 TI - In the clinic. Smoking cessation. PMID- 17283346 TI - Diagnosis and initial management of obstructive sleep apnea without polysomnography: a randomized validation study. AB - BACKGROUND: Polysomnography (PSG), despite limited availability and high cost, is currently recommended for diagnosis of obstructive sleep apnea and titration of effective continuous positive airway pressure (CPAP). OBJECTIVE: To test the utility of a diagnostic algorithm in conjunction with ambulatory CPAP titration in initial management of obstructive sleep apnea. DESIGN: A randomized, controlled, open-label trial that compared standard PSG with ambulatory CPAP titration in high-risk patients identified by a diagnostic algorithm. SETTING: A tertiary referral sleep disorders program in Vancouver, British Columbia, Canada. PATIENTS: 68 patients with a high pretest probability of moderate to severe obstructive sleep apnea (apnea-hypopnea index [AHI] >15 episodes/h) identified by sequential application of the Epworth Sleepiness Scale (ESS) score, Sleep Apnea Clinical Score, and overnight oximetry. INTERVENTION: Patients were randomly assigned to PSG or ambulatory titration by using a combination of auto-CPAP and overnight oximetry. They were observed for 3 months. MEASUREMENTS: Apnea-hypopnea index on CPAP, ESS score, quality of life, and CPAP adherence. RESULTS: The PSG and ambulatory groups had similar median BMI (38 kg/m2), age (55 years), ESS score (14 points), and respiratory disturbance index (31 episodes of respiratory disturbance/h). Each episode is determined by a computer algorithm based on analysis of oxygen saturation measured by pulse oximetry. After 3 months, there were no differences in the primary outcome, AHI on CPAP (median, 3.2 vs. 2.5; difference, 0.8/h [95% CI, -0.9 to 2.3]) (P = 0.31), between the PSG and ambulatory groups, or in the secondary outcomes, ESS score, Sleep Apnea Quality of Life Index, and CPAP. Adherence to CPAP therapy was better in the ambulatory group than in the PSG group (median, 5.4 vs. 6.0; difference, -1.12 h/night [CI, 2.0 to 0.2]) (P = 0.021). CONCLUSIONS: In the initial management of patients with a high probability of obstructive sleep apnea, PSG confers no advantage over the ambulatory approach in terms of diagnosis and CPAP titration. The ambulatory approach may improve adherence to treatment. When access to PSG is inadequate, the ambulatory approach can be used to expedite management of patients most in need of treatment. PMID- 17283347 TI - Brief intervention for medical inpatients with unhealthy alcohol use: a randomized, controlled trial. AB - BACKGROUND: The efficacy of brief intervention in reducing alcohol consumption is well established for selected outpatients but not for medical inpatients. OBJECTIVE: To determine whether brief intervention improves alcohol outcomes in medical inpatients who were identified by screening as having unhealthy alcohol use. DESIGN: Randomized, controlled trial. SETTING: Medical service of an urban hospital. PATIENTS: 341 medical inpatients who were drinking risky amounts of alcohol (defined for eligibility as >14 drinks/wk or > or =5 drinks/occasion for men and >11 drinks/wk or > or =4 drinks/occasion for women and persons > or =66 y); 77% had alcohol dependence as determined by the Composite International Diagnostic Interview Alcohol Module. INTERVENTION: A 30-minute session of motivational counseling given by trained counselors during a patient's hospitalization (n = 172) versus usual care (n = 169). MEASUREMENTS: Self reported primary outcomes were receipt of alcohol assistance (for example, alcohol disorders specialty treatment) by 3 months in dependent drinkers and change in the mean number of drinks per day from enrollment to 12 months in all patients. RESULTS: The intervention was not significantly associated with receipt of alcohol assistance by 3 months among alcohol-dependent patients (adjusted proportions receiving assistance, 49% for the intervention group and 44% for the control group; intervention-control difference, 5% [95% CI, -8% to 19%]) or with drinks per day at 12 months among all patients (adjusted mean decreases, 1.5 for patients who received the intervention and 3.1 for patients who received usual care; adjusted mean group difference, -1.5 [CI, -3.7 to 0.6]). There was no significant interaction between the intervention and alcohol dependence in statistical models predicting drinks per day (P = 0.24). LIMITATIONS: Baseline imbalances existed between randomized groups. Patients who received usual care were assessed and advised that they could discuss their drinking with their physicians. CONCLUSIONS: Brief intervention is insufficient for linking medical inpatients with treatment for alcohol dependence and for changing alcohol consumption. Medical inpatients with unhealthy alcohol use require more extensive, tailored alcohol interventions. PMID- 17283348 TI - Octogenarians and nonagenarians starting dialysis in the United States. AB - BACKGROUND: The elderly constitute the fastest-growing segment of the end-stage renal disease (ESRD) population, but the epidemiology and outcomes of dialysis among the very elderly, that is, those 80 years of age and older, have not been previously examined at a national level. OBJECTIVE: To describe recent trends in the incidence and outcomes of octogenarians and nonagenarians starting dialysis. DESIGN: Observational study. SETTING: U.S. Renal Data System, a comprehensive, national registry of patients with ESRD. PARTICIPANTS: Octogenarians and nonagenarians initiating dialysis between 1996 and 2003. MEASUREMENTS: Rates of dialysis initiation and survival. RESULTS: The number of octogenarians and nonagenarians starting dialysis increased from 7054 persons in 1996 to 13,577 persons in 2003, corresponding to an average annual increase in dialysis initiation of 9.8%. After we accounted for population growth, the rate of dialysis initiation increased by 57% (rate ratio, 1.57 [95% CI, 1.53 to 1.62]) between 1996 and 2003. One-year mortality for octogenarians and nonagenarians after dialysis initiation was 46%. Compared with octogenarians and nonagenarians initiating dialysis in 1996, those starting dialysis in 2003 had a higher glomerular filtration rate and less morbidity related to chronic kidney disease but no difference in 1-year survival. Clinical characteristics strongly associated with death were older age, nonambulatory status, and more comorbid conditions. LIMITATIONS: Survival of patients with incident ESRD who did not begin dialysis could not be assessed. CONCLUSIONS: The number of octogenarians and nonagenarians initiating dialysis has increased considerably over the past decade, while overall survival for patients on dialysis remains modest. Estimates of prognosis based on patient characteristics, when considered in conjunction with individual values and preferences, may aid in dialysis decision making for the very elderly. PMID- 17283349 TI - Brief communication: Preoperative anticoagulant activity after bridging low molecular-weight heparin for temporary interruption of warfarin. AB - BACKGROUND: Preoperative low-molecular-weight heparin (LMWH) is often used when warfarin therapy is interrupted for surgery. OBJECTIVE: To determine the preoperative anticoagulant activity of LMWH following a standardized "bridging" regimen. DESIGN: Prospective cohort study. SETTING: Single university hospital. PATIENTS: Consecutive patients who had warfarin therapy interrupted before an invasive procedure. INTERVENTION: Enoxaparin, 1 mg/kg of body weight, twice daily. The last dose was administered the evening before surgery. MEASUREMENTS: Blood anti-factor Xa heparin levels measured shortly before surgery. RESULTS: Preoperative anti-Xa heparin levels were obtained in 80 patients at an average of 14 hours after the last dose of enoxaparin was administered. The average anti-Xa heparin level was 0.6 U/mL. The anti-Xa heparin level, measured shortly before surgery, was 0.5 U/mL or greater in 54 (68%) patients and 1.0 U/mL or greater in 13 (16%) patients. A shorter interval since the last dose (P < 0.001) and a higher body mass index (P = 0.001) were associated with higher preoperative anti Xa heparin levels. LIMITATIONS: The small sample size limits accurate estimates of the frequency of the clinical outcomes. A single regimen of LMWH was evaluated. CONCLUSIONS: Anti-Xa heparin levels often remain high at the time of surgery if a last dose of a twice-daily regimen of LMWH is given the evening before surgery. PMID- 17283350 TI - Brief communication: National quality-of-care standards in home-based primary care. AB - BACKGROUND: Home-based primary care for homebound seniors is complex, and practice constraints are unique. No quality-of-care standards exist. OBJECTIVE: To identify process quality indicators that are essential to high-quality, home based primary care. DESIGN: An expert development panel reviewed established and new quality indicators for applicability to home-based primary care. A separate national evaluation panel used a modified Delphi process to rate the validity and importance of the potential quality indicators. PARTICIPANTS: Two national panels whose members varied in practice type, location, and setting. RESULTS: The panels considered 260 quality indicators and endorsed 200 quality indicators that cover 23 geriatric conditions. Twenty-one (10.5%) quality indicators were newly created, 52 (26%) were modified, and 127 (63.5%) were unchanged. The quality indicators have decreased emphasis on interventions and have placed greater emphasis on quality of life. LIMITATIONS: The quality indicator set may not apply to all homebound seniors and might be difficult to implement for a typical home based primary care program. CONCLUSIONS: The quality indicator set provides a comprehensive home-based primary care quality framework and will allow for future comparative research. Provision of these evidence-based measures could improve patient quality of life and longevity. PMID- 17283351 TI - Meta-analysis: intravenous immunoglobulin in critically ill adult patients with sepsis. AB - BACKGROUND: Intravenous immunoglobulin therapy has been proposed as an adjuvant treatment for sepsis. Yet, its benefit remains unclear, and its use is not currently recommended. PURPOSE: To evaluate the effect of polyclonal intravenous immunoglobulin therapy on death in critically ill adult patients with sepsis. DATA SOURCES: MEDLINE (1966 to May 2006) and the Cochrane Central Register of Controlled Trials (May 2006 edition). STUDY SELECTION: All randomized, controlled trials of critically ill adult patients with sepsis, severe sepsis, or septic shock who received polyclonal intravenous immunoglobulin therapy or placebo or no intervention were selected. No restrictions were made for study language or type of publication. DATA EXTRACTION: Data were independently extracted by 2 investigators using a standardized form. DATA SYNTHESIS: The literature search identified 4096 articles, of which 33 were deemed to be potentially eligible. Twenty trials (n = 2621) met eligibility criteria and were included in the analysis. Polyclonal intravenous immunoglobulin therapy was associated with an overall survival benefit (risk ratio, 0.74 [95% CI, 0.62 to 0.89]) compared with placebo or no intervention. In sensitivity analyses, documented survival improved when the analysis was limited to published, peer-reviewed trials (risk ratio, 0.72 [CI, 0.58 to 0.89]) (17 trials [n = 1865]) and blinded trials (risk ratio, 0.61 [CI, 0.40 to 0.93) (7 trials [n = 896]). Severe sepsis or septic shock (risk ratio, 0.64 [CI, 0.52 to 0.79]) (11 trials [n = 689]), receiving a total dose regimen of 1 gram or more per kilogram of body weight (risk ratio, 0.61 [CI, 0.40 to 0.94]) (7 trials [n = 560]), and receiving therapy for longer than 2 days (risk ratio, 0.66 [CI, 0.53 to 0.82]) (17 trials [n = 1847]) were strongly associated with this survival benefit. LIMITATIONS: Most trials were published before new developments modifying the care and outcome of critically ill patients with sepsis including early goal-directed therapy and activated protein C treatment, were introduced. CONCLUSIONS: A survival benefit was observed for patients with sepsis who received polyclonal intravenous immunoglobulin therapy compared with those who received placebo or no intervention. A large, randomized, controlled trial of polyclonal intravenous immunoglobulin therapy should be performed on the basis of the methodological limitations of the current literature, the potential benefit from this therapy in more severely ill patients, and the potential effect of dosage and duration of this therapy. PMID- 17283352 TI - Brief interventions for problem drinking: another piece of the puzzle. PMID- 17283353 TI - Squatter Sam and professionalism. PMID- 17283354 TI - Squatter Sam. PMID- 17283355 TI - Erythropoietin, gadolinium, and nephrogenic fibrosing dermopathy. PMID- 17283356 TI - Effects of coffee and napping on nighttime highway driving. PMID- 17283357 TI - Development of coronary aneurysm after drug-eluting stent implantation. PMID- 17283358 TI - One-to-one counselling for STI prevention: not so much whether as how. PMID- 17283359 TI - Risk reduction counselling for prevention of sexually transmitted infections: how it works and how to make it work. AB - Prevention research in the past decade has proved the efficacy of risk reduction counselling in reducing the risks for sexually transmitted infections (STIs). The question currently facing STI service providers is therefore not so much whether counselling should be part of the standard of STI care but rather how this intervention can be implemented given the logistical and resource constraints of a busy practice setting. After a brief introduction of the history and an overview of the models for risk reduction counselling and their theoretical and scientific underpinnings, the focus of this paper will be on the extent to which individual prevention models have been adopted in different clinical settings, the impediments to implementation and suggestions for improvement. PMID- 17283361 TI - Positive serological tests for syphilis and administration of intravenous immunoglobulin. AB - We report the case of a man who tested positive for syphilis following the intravenous administration of human normal immunoglobulin as part of the treatment of Guillain-Barre syndrome. The chronology of the testing suggested the passive acquisition of treponemal antibody. This phenomenon is not widely documented in the medical literature, but is a theoretical risk of treatment, and serves as a reminder to be cautious in the interpretation of such serological tests. PMID- 17283360 TI - Maintenance of endemicity in urban environments: a hypothesis linking risk, network structure and geography. AB - In industrialised countries, a rapid epidemic phase of HIV transmission has largely given way to more moderated endemic transmission. The dynamics of endemic transmission may differ substantially from those generating epidemic spread. We hypothesise that three elements play an important role in maintaining endemicity in high prevalence urban environments. First, persons are likely to be subject to multiple risks from multiple sources rather than engaging in a single, hierarchically classified, risk behaviour. Second, the network structure in these environments may include a substrate of "fixed" factors (a large connected component, a characteristic degree distribution and small world phenomenon) upon which is superimposed a number of variable factors (transitivity, assortativity) that determine the level of prevalence. Third, the geographic range of persons in these milieux is constricted, making it likely that new partners will already be connected. The confluence of these three factors assures the ongoing risk bombardment needed for maintenance of endemicity. Further empirical and theoretical analysis will be required in order to validate this hypothesis. PMID- 17283362 TI - The first four years of the foundation course on sexually transmitted infections. PMID- 17283364 TI - Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. AB - PURPOSE: The combination of fludarabine and cyclophosphamide is an effective regimen for patients with chronic lymphocytic leukemia (CLL). However, it may be accompanied by increased toxicity compared with fludarabine alone. E2997 is a phase III randomized Intergroup trial comparing fludarabine and cyclophosphamide (FC arm) versus fludarabine (F arm) alone in patients receiving their first chemotherapy regimen for CLL. PATIENTS AND METHODS: Symptomatic, previously untreated patients with CLL were randomly assigned to receive either fludarabine 25 mg/m2 intravenously (IV) days 1 through 5 or cyclophosphamide 600 mg/m2 IV day 1 and fludarabine 20 mg/m2 IV days 1 through 5. These cycles were repeated every 28 days for a maximum of six cycles. RESULTS: A total of 278 patients were randomly assigned in this Intergroup study. Treatment with fludarabine and cyclophosphamide was associated with a significantly higher complete response (CR) rate (23.4% v 4.6%; P < .001) and a higher overall response (OR) rate (74.3% v 59.5%, P = .013) than treatment with fludarabine as a single agent. Progression free survival (PFS) was also superior in patients treated with fludarabine and cyclophosphamide than those treated with fludarabine (31.6 v 19.2 months, P < .0001). Fludarabine and cyclophosphamide caused additional hematologic toxicity, including more severe thrombocytopenia (P = .046), but it did not increase the number of severe infections (P = .812). CONCLUSION: Fludarabine and cyclophosphamide produced an increase in OR and CR, and it improved PFS in patients with previously untreated CLL compared with fludarabine alone and was not associated with an increase in infectious toxicity. PMID- 17283363 TI - Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. AB - PURPOSE: Genomic features including unmutated immunoglobulin variable region heavy chain (IgVH) genes, del(11q22.3), del(17p13.1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome. PATIENTS AND METHODS: We prospectively evaluated the prognostic significance of a comprehensive panel of laboratory factors on both response and progression-free survival (PFS) using samples and data from 235 patients enrolled onto a therapeutic trial. Patients received either fludarabine (FL; n = 113) or fludarabine plus cyclophosphamide (FC; n = 122) as part of a US Intergroup randomized trial for previously untreated CLL patients. RESULTS: Complete response (CR) rates were 24.6% for patients receiving FC and 5.3% for patients receiving FL (P = .00004). PFS was statistically significantly longer in patients receiving FC (median, 33.5 months for patients receiving FC and 19.9 months for patients receiving FL; P < .0001). The occurrence of del(17p13.1) (hazard ratio, 3.428; P = .0002) or del(11q22.3) (hazard ratio, 1.904; P = .006) was associated with reduced PFS. CR and overall response rates were not significantly different based on cytogenetics, IgVH mutational status, CD38 expression, or p53 mutational status. Expression of ZAP 70, Bcl-2, Bax, Mcl-1, XIAP, Caspase-3, and Traf-1 was not associated with either clinical response or PFS. CONCLUSION: These results support the use of interphase cytogenetic analysis, but not IgVH, CD38 expression, or ZAP-70 status, to predict outcome of FL-based chemotherapy. Patients with high-risk cytogenetic features should be considered for alternative therapies. PMID- 17283365 TI - Evolution of a pseudogene: exclusive survival of a functional mitochondrial nad7 gene supports Haplomitrium as the earliest liverwort lineage and proposes a secondary loss of RNA editing in Marchantiidae. AB - Gene transfer from the mitochondrion into the nucleus is a corollary of the endosymbiont hypothesis. The frequent and independent transfer of genes for mitochondrial ribosomal proteins is well documented with many examples in angiosperms, whereas transfer of genes for components of the respiratory chain is a rarity. A notable exception is the nad7 gene, encoding subunit 7 of complex I, in the liverwort Marchantia polymorpha, which resides as a full-length, intron carrying and transcribed, but nonspliced pseudogene in the chondriome, whereas its functional counterpart is nuclear encoded. To elucidate the patterns of pseudogene degeneration, we have investigated the mitochondrial nad7 locus in 12 other liverworts of broad phylogenetic distribution. We find that the mitochondrial nad7 gene is nonfunctional in 11 of them. However, the modes of pseudogene degeneration vary: whereas point mutations, accompanied by single nucleotide indels, predominantly introduce stop codons into the reading frame in marchantiid liverworts, larger indels introduce frameshifts in the simple thalloid and leafy jungermanniid taxa. Most notably, however, the mitochondrial nad7 reading frame appears to be intact in the isolated liverwort genus Haplomitrium. Its functional expression is shown by cDNA analysis identifying typical RNA-editing events to reconstitute conserved codon identities and also confirming functional splicing of the 2 liverwort-specific group II introns. We interpret our results 1) to indicate the presence of a functional mitochondrial nad7 gene in the earliest land plants and strongly supporting a basal placement of Haplomitrium among the liverworts, 2) to indicate different modes of pseudogene degeneration and chondriome evolution in the later branching liverwort clades, 3) to suggest a surprisingly long maintenance of a nonfunctional gene in the presumed oldest group of land plants, and 4) to support the model of a secondary loss of RNA-editing activity in marchantiid liverworts. PMID- 17283366 TI - Independent duplications of the acetylcholinesterase gene conferring insecticide resistance in the mosquito Culex pipiens. AB - Gene duplication is thought to be the main potential source of material for the evolution of new gene functions. Several models have been proposed for the evolution of new functions through duplication, most based on ancient events (Myr). We provide molecular evidence for the occurrence of several (at least 3) independent duplications of the ace-1 locus in the mosquito Culex pipiens, selected in response to insecticide pressure that probably occurred very recently (<40 years ago). This locus encodes the main target of several insecticides, the acetylcholinesterase. The duplications described consist of 2 alleles of ace-1, 1 susceptible and 1 resistant to insecticide, located on the same chromosome. These events were detected in different parts of the world and probably resulted from distinct mechanisms. We propose that duplications were selected because they reduce the fitness cost associated with the resistant ace-1 allele through the generation of persistent, advantageous heterozygosis. The rate of duplication of ace-1 in C. pipiens is probably underestimated, but seems to be rather high. PMID- 17283368 TI - Tight junction proteins in gallbladder epithelium: different expression in acute acalculous and calculous cholecystitis. AB - There is a paucity of information of tight junction (TJ) proteins in gallbladder epithelium, and disturbances in the structure of these proteins may play a role in the pathogenesis of acute acalculous cholecystitis (AAC) and acute calculous cholecystitis (ACC). Using immunohistochemistry, we investigated the expression of TJ proteins claudin-1, -2, -3, and -4, occludin, zonula occludens (ZO-1), and E-cadherin in 9 normal gallbladders, 30 gallbladders with AAC, and 21 gallbladders with ACC. The number of positive epithelial and endothelial cells and the intensity of the immunoreaction were determined. Membrane-bound and cytoplasmic immunoreactivities were separately assessed. We found that TJ proteins were uniformly expressed in normal gallbladder epithelium, with the exception of claudin-2, which was present in less than half of the cells. In AAC, expression of cytoplasmic occludin and claudin-1 were decreased, as compared with normal gallbladder. In ACC, expression of claudin-2 was increased, and expression of claudin-1, -3, and -4, occludin, and ZO-1 were decreased, as compared with normal gallbladder or AAC. We conclude that there are significant differences in expression of TJ proteins in AAC and ACC, supporting the idea that AAC represents a manifestation of systemic inflammatory disease, whereas ACC is a local inflammatory and often infectious disease. PMID- 17283367 TI - Dietary fat stimulates endogenous enkephalin and dynorphin in the paraventricular nucleus: role of circulating triglycerides. AB - The opioid peptides enkephalin (ENK) and dynorphin (DYN), when injected into the hypothalamus, are known to stimulate feeding behavior and preferentially increase the ingestion of a high-fat diet. Studies of another peptide, galanin (GAL), with similar effects on feeding demonstrate that a high-fat diet, in turn, can stimulate the expression of this peptide in the hypothalamus. The present study tested different diets and variable periods of high- vs. low-fat diet consumption to determine whether the opioid peptides respond in a similar manner as GAL. In six experiments, the effects of dietary fat on ENK and DYN were examined in three hypothalamic areas: the paraventricular nucleus (PVN), perifornical hypothalamus (PFH), and arcuate nucleus (ARC). The results demonstrated that the ingestion of a high-fat diet increases gene expression and peptide levels of both ENK and DYN in the hypothalamus. The strongest and most consistent effect is seen in the PVN. In this nucleus, ENK and DYN are increased by 50-100% after 1 wk, 1 day, 60 min, and even 15 min of high-fat diet consumption. While showing some effect in the PFH, these peptides in the ARC are considerably less responsive, exhibiting no change in response to the briefer periods of diet intake. This effect of dietary fat on PVN opioids can be observed with diets equal in caloric density and palatability and without a change in caloric intake, body weight, fat pad weight, or levels of insulin or leptin. The data reveal a strong and consistent association between these peptides and a rise in circulating levels of triglycerides, supporting a role for these lipids in the fat-induced stimulation of opioid peptides in the PVN, similar to GAL. PMID- 17283369 TI - Localization of immunoreactive gonadotropin-releasing hormone and relative expression of its mRNA in the oviduct during pregnancy in rats. AB - This study was designed to determine the cellular and ultrastructural distribution of the gonadotropin-releasing hormone (GnRH) and the relative expression of its mRNA in the oviduct of rats during different time points (days 7, 9, 16, and 20) of pregnancy. Immunofluorescent localization and confocal microscopic techniques were used to determine the cellular distribution of GnRH in the oviduct. Immunogold electron microscopy indicated its localization at the ultrastructural level, and real-time PCR was used to study the expression pattern of GnRH mRNA in the oviduct during pregnancy. In general, GnRH was localized within the epithelial cells lining the oviductal lumen at each selected time point. A strong correlation between the fluorescence intensity of GnRH immunoreactive cells and the relative expression of GnRH mRNA was noted on days 7 and 16, followed by a plateau by day 20. At the ultrastructural level, uniform labeling of colloidal gold particles was observed in secretory vesicles and lamella of the luminal epithelium as well as the lumen of the oviduct. Collectively, these results demonstrate for the first time that the oviductal epithelium synthesizes and secretes the decapeptide GnRH during pregnancy in rats, which may have a possible role in postimplantation embryonic development and the maintenance of pregnancy. PMID- 17283370 TI - Immunohistochemical evidence for the presence of glucokinase in the gonadotropes and thyrotropes of the anterior pituitary gland of rat and monkey. AB - A recent report provides new evidence for the presence of glucokinase (GK) in the anterior pituitary. In the present study, immunohistochemistry was used to identify the cells containing GK in the pituitary of rats and monkeys. In rats, GK was detected as a generalized cytoplasmic staining in a discrete population of cells in the anterior pituitary. In colocalization experiments, the majority of cells expressing follicle-stimulating hormone (FSH) or luteinizing hormone (LH) also contained GK. In addition to the gonadotropes, GK was observed in a subpopulation of corticotropes and thyrotropes. GK was not detected in cells expressing growth hormone or prolactin. In monkeys, GK was also observed in a discrete population of cells. Intracellular distribution differed from the rat in that GK in most cells was concentrated in a perinuclear location that appeared to be associated with the Golgi apparatus. However, similar to rats, colocalization experiments showed that the majority of cells expressing FSH or LH also contained GK. In addition to the gonadotropes, GK was observed in a subpopulation of corticotropes and thyrotropes. In the monkey, only a few cells had generalized cytoplasmic staining for GK. These experiments provide further evidence for the presence of GK in the anterior pituitary. Although some corticotropes and thyrotropes contained GK, the predominant cell type expressing GK was gonadotropes. In view of the generally accepted role of GK as a glucose sensor in a variety of cells including the insulin-producing pancreatic beta-cells as the prototypical example, it is hypothesized that hormone synthesis and/or release in pituitary cells containing GK may be directly influenced by blood glucose. PMID- 17283371 TI - Morphological variation in tomato: a comprehensive study of quantitative trait loci controlling fruit shape and development. AB - Variation in fruit morphology is a prevalent characteristic among cultivated tomato. The genetic and developmental mechanisms underlying similarities and differences in shape between the fruit of two elongated tomato varieties were investigated. Fruit from two F2 populations constructed from either Solanum lycopersicum cv. Howard German or cv. Banana Legs crossed with S. pimpinellifolium accession LA1589, and one BC1 population constructed with S. lycopersicum Howard German as the recurrent parent, were analysed for shape by using a new software program Tomato Analyzer. Quantitative trait loci (QTLs) controlling 15 individual shape attributes were mapped by both single and multitrait composite interval mapping in each population. In addition, principal components analysis and canonical discriminant analysis were conducted on these shape attributes to determine the greatest sources of variation among and between the populations. Individual principal components and canonical variates were subjected to QTL analysis to map regions of the genome influencing fruit shape in the cultivars. Common and unique regions, as well as previously known and novel QTLs, underlying fruit morphology in tomato were identified. Four major loci were found to control multiple fruit shape traits, principal components, and canonical variates in the populations. In addition, QTLs associated with the principal components better revealed regions of the genome that varied among populations than did the QTL associated with canonical variates. The QTL identified can be compared across additional populations of tomato and other fruit-bearing crop species. PMID- 17283372 TI - Can arsenic-phytochelatin complex formation be used as an indicator for toxicity in Helianthus annuus? AB - The formation of arsenic-phytochelatin (As-PC) complexes is thought to be part of the plant detoxification strategy for arsenic. This work examines (i) the arsenic (As) concentration-dependent formation of As-PC complex formation and (ii) redistribution and metabolism of As after arrested As uptake in Helianthus annuus. HPLC with parallel ICP-MS/ES-MS detection was used to identify and quantify the species present in plant extracts exposed to arsenate (As(V)) (between 0 and 66.7 micromol As l-1 for 24 h). At As concentrations below the EC50 value for root growth (22 micromol As l-1) As uptake is exponential, but it is reduced at concentrations above. Translocation between root and shoot seemed to be limited to the uptake phase of arsenic. No redistribution of As between root and shoot was observed after arresting As exposure. The formation of As-PC complexes was concentration-dependent. The amount and number of As-PC complexes increased exponentially with concentration up to 13.7 micromol As l-1. As(III) PC3 and GS-As(III)-PC2 complexes were the dominant species in all samples. The ratio of PC-bound As to unbound As increased up to 1.3 micromol As l-1 and decreased at higher concentrations. Methylation of inorganic As was only a minor pathway in H. annuus with about 1% As methylated over a 32 d period. The concentration dependence of As-PC complex formation, amount of unbound reduced and oxidized PC2, and the relative uptake rate showed that As starts to influence the cellular metabolism of H. annuus negatively at As concentrations well below the EC50 value determined by more traditional means. Generally, As-PC complexes and PC-synthesis rate seem to be the more sensitive parameters to be studied when As toxicity values are to be estimated. PMID- 17283373 TI - Effects of carbon dioxide and oxygen on sapwood respiration in five temperate tree species. AB - The gaseous environment surrounding parenchyma in woody tissue is low in O2 and high in CO2, but it is not known to what extent this affects respiration or might play a role in cell death during heartwood formation. Sapwood respiration was measured in two conifers and three angiosperms following equilibration to levels of O2 and CO2 common within stems, using both inner and outer sapwood to test for an effect of age. Across all species and tissue ages, lowering the O2 level from 10% to 5% (v/v) resulted in about a 25% decrease in respiration in the absence of CO2, but a non-significant decrease at 10% CO2. The inhibitory effect of 10% CO2 was smaller and only significant at 10% O2, where it reduced respiration by about 14%. Equilibration to a wider range of gas combinations in Pinus strobus L. showed the same effect: 10% CO2 inhibited respiration by about 15% at both 20% and 10% O2, but had no net effect at 5% O2. In an extreme treatment, 1% O2+20% CO2 increased respiration by over 30% relative to 1% O2 alone, suggesting a shift in metabolic response to high CO2 as O2 decreases. Although an increase in respiration would be detrimental under limiting O2, this extreme gas combination is unlikely to exist within most stems. Instead, moderate reductions in respiration under realistic O2 and CO2 levels suggest that within-stem gas composition does not severely limit respiration and is unlikely to cause the death of xylem parenchyma during heartwood formation. PMID- 17283374 TI - Salt tolerance in a Hordeum marinum-Triticum aestivum amphiploid, and its parents. AB - Growth, grain production, and physiological traits were evaluated for Hordeum marinum, Triticum aestivum (cv. Chinese Spring), and a H. marinum-T. aestivum amphiploid, when exposed to NaCl treatments in a nutrient solution. H. marinum was more salt tolerant than T. aestivum and the amphiploid was intermediate, both for vegetative growth and relative grain production. H. marinum was best able to 'exclude' Na(+) and Cl(-), particularly at high external NaCl. At 300 mM NaCl, concentrations of Na(+) (153 micromol g(-1) dry mass) and Cl(-) (75 micromol g( 1) dry mass) in the youngest fully-expanded leaf blade of H. marinum were, respectively, only 7% and 4% of those in T. aestivum; and in the amphiploid the Na(+) and Cl(-) concentrations were 39% and 36% of those in T. aestivum. Glycinebetaine and proline concentrations in the youngest fully-expanded leaf blade of plants exposed to 200 mM NaCl were highest in H. marinum (128 and 60 micromol g(-1) dry mass, respectively), lowest in T. aestivum (85 and 37 micromol g(-1) dry mass), and intermediate in the amphiploid (108 and 54 micromol g(-1) dry mass). Thus, salt tolerance of H. marinum was expressed in the H. marinum-T. aestivum amphiploid. PMID- 17283375 TI - Inhibition of photosynthesis and energy dissipation induced by water and high light stresses in rice. AB - Photoprotection mechanisms of rice plants were studied when its seedlings were subjected to the combined stress of water and high light. The imposition of water stress, induced by PEG 6000 which was applied to roots, resulted in substantial inhibition of stomatal conductance and net photosynthesis under all irradiance treatments. Under high light stress, the rapid decline of photosynthesis with the development of water stress was accompanied by decreases in the maximum velocity of RuBP carboxylation by Rubisco (V(cmax)), the capacity for ribulose-1,5 bisphosphate regeneration (J(max)), Rubisco and stromal FBPase activities, and the quantum efficiency of photosystem II, in the absence of any stomatal limitation of CO(2) supply. Water stress significantly reduced the energy flux via linear electron transport (J(PSII)), but increased light-dependent and DeltapH- and xanthophyll-mediated thermal dissipation (J(NPQ)). It is concluded that the drought-induced inhibition of photosynthesis under different irradiances in the rice was due to both diffusive and metabolic limitations. Metabolic limitation of photosynthesis may be related to the adverse effects of some metabolic processes and the oxidative damage to the chloroplast. Meanwhile, an enhanced thermal dissipation is an important process to minimize the adverse effects of drought and high irradiance when CO(2) assimilation is suppressed. PMID- 17283376 TI - Towards a virtual fruit focusing on quality: modelling features and potential uses. AB - The fruit is a hierarchically organized organ composed of cells from different tissues. Its quality, defined by traits such as fruit size and composition, is the result of a complex chain of biological processes. These processes involve exchanges (transpiration, respiration, photosynthesis, phloem and xylem fluxes, and ethylene emission) between the fruit and its environment (atmosphere or plant), tissue differentiation, and cell functioning (division, endoreduplication, expansion, metabolic transformations, and vacuolar storage). In order to progress in our understanding of quality development, it is necessary to analyse the fruit as a system, in which processes interact. In this case, a process-based modelling approach is particularly powerful. Such a modelling approach is proposed to develop a future 'virtual fruit' model. The value of a virtual fruit for agronomists and geneticists is also discussed. PMID- 17283377 TI - Water properties in fern spores: sorption characteristics relating to water affinity, glassy states, and storage stability. AB - Ex situ conservation of ferns may be accomplished by maintaining the viability of stored spores for many years. Storage conditions that maximize spore longevity can be inferred from an understanding of the behaviour of water within fern spores. Water sorption properties were measured in spores of five homosporeous species of ferns and compared with properties of pollen, seeds, and fern leaf tissue. Isotherms were constructed at 5, 25, and 45 degrees C and analysed using different physicochemical models in order to quantify chemical affinity and heat (enthalpy) of sorption of water in fern spores. Fern spores hydrate slowly but dry rapidly at ambient relative humidity. Low Brunauer-Emmet-Teller monolayer values, few water-binding sites according to the D'Arcy-Watt model, and limited solute-solvent compatibility according to the Flory-Huggins model suggest that fern spores have low affinity for water. Despite the low water affinity, fern spores demonstrate relatively high values of sorption enthalpy (DeltaH(sorp)). Parameters associated with binding sites and DeltaH(sorp) decrease with increasing temperature, suggesting temperature- and hydration-dependent changes in volume of spore macromolecules. Collectively, these data may relate to the degree to which cellular structures within fern spores are stabilized during drying and cooling. Water sorption properties within fern spores suggest that storage at subfreezing temperatures will give longevities comparable with those achieved with seeds. However, the window of optimum water contents for fern spores is very narrow and much lower than that measured in seeds, making precise manipulation of water content imperative for achieving maximum longevity. PMID- 17283378 TI - Arsenic as an endocrine disruptor: effects of arsenic on estrogen receptor mediated gene expression in vivo and in cell culture. AB - Arsenic (As) contamination of drinking water is considered a serious worldwide environmental health threat that is associated with increased disease risks including skin, lung, bladder, and other cancers; type 2 diabetes; vascular and cardiovascular diseases; reproductive and developmental effects; and neurological and cognitive effects. Increased health risks may occur at as low as 10-50 ppb, while biological effects have been observed in experimental animal and cell culture systems at much lower levels. We previously reported that As is a potent endocrine disruptor, altering gene regulation by the closely related glucocorticoid, mineralocorticoid, progesterone, and androgen steroid receptors (SRs) at concentrations as low as 0.01 microM ( approximately 0.7 ppb). Very low doses enhanced hormone-mediated gene transcription, whereas slightly higher but still noncytotoxic doses were suppressive. We report here that As also disrupts the more distally related estrogen receptor (ER) both in vivo and in cell culture. At noncytotoxic doses (1-50 micromol/kg arsenite) As strongly suppressed ER-dependent gene transcription of the 17beta-estradiol (E2)-inducible vitellogenin II gene in chick embryo liver in vivo. In cell culture, noncytotoxic levels (0.25-3 microM, approximately 20-225 ppb) of As significantly inhibited E2 mediated gene activation of an ER-regulated reporter gene and the native ER regulated GREB1 gene in human breast cancer MCF-7 cells. While the effects of As on ER-dependent gene regulation were generally similar to As effects on the other SRs, there were specific differences, particularly the lack of significant enhancement at the lowest doses, that may provide insights into possible mechanisms. PMID- 17283379 TI - Induction of cytochrome P450 1A1 by ketoconazole and itraconazole but not fluconazole in murine and human hepatoma cell lines. AB - Azole antifungal agents are widely prescribed drugs for the treatment of systemic fungal infections; however, since their introduction into the market, increasing evidences of hepatotoxicity have been reported. Therefore, we examined here the ability of three structurally different antifungal drugs, ketoconazole (KTZ), itraconazole (ITZ), and fluconazole (FLZ) to induce the CYP1A1, an enzyme known to play an important role in chemical activation of xenobiotics to toxic metabolites. KTZ and ITZ, but not FLZ, induced the CYP1A1 in murine Hepa 1c1c7 and human HepG2 hepatoma cells at the mRNA, protein and activity levels in a concentration- and time-dependent manner. The increases in Cyp1a1 mRNA levels mediated by KTZ and ITZ were completely blocked by the RNA synthesis inhibitor, actinomycin D, whereas the level of existing mRNA was not altered, implying a requirement of de novo RNA synthesis through a transcriptional mechanism. The ability of these drugs to directly activate the aryl hydrocarbon receptor (AhR) transformation and hence xenobiotic responsive element's binding was strongly correlated with their abilities to induce luciferase activity. Inhibition studies showed that KTZ and ITZ, in addition to being CYP1A1 inducers, are substrates and competitive inhibitors. This study provides the first evidence for the ability of KTZ and ITZ to induce the CYP1A1 gene expression through an AhR-dependent mechanism, and suggests a novel mechanism of the KTZ- and ITZ-mediated toxicities. PMID- 17283381 TI - Diagnostic performance of serum total testosterone for Japanese patients with polycystic ovary syndrome. AB - It is reported that the incidence of clinical and biochemical hyperandrogenism may be lower in Japanese patients with PCOS. Hyperandrogenism is included as a referential but not as an essential factor in the diagnostic criteria of the Japanese Society of Obstetrics and Gynecology (JSOG 1993). However, some patients with the typical clinical features of PCOS are not diagnosed with PCOS using JSOG 1993 criteria because they do not have a high LH level, which is defined as essential for diagnosis. In this study, we compared total testosterone (T) levels between Japanese patients with PCOS diagnosed using the JSOG 1993 criteria and normal menstrual women (controls). Fifty controls and 46 patients with PCOS were enrolled in this study. Furthermore, we evaluated the sensitivity and specificity of each cut-off value of T. The mean T level of patients with PCOS was significantly higher than that of the control (86 +/- 48 vs 68 +/- 46, P<0.01), and the prevalence rates of hyperandrogenism (T >114 ng/dL; defined as the mean +2SD of the control) were 10.2% in patients with PCOS and 4% in controls. The area under the ROC curve of T was 0.72, and there was no decision threshold to diagnose PCOS by T alone with both high sensitivity and high specificity. If the threshold is set as 110 ng/dL in order to gain high specificity, 94% of women whose serum level passed the threshold will be patients with PCOS. Although T should not be used as an independent essential factor of Japanese PCOS, it might be useful as a complementary factor in order to diagnose patients who have typical clinical features of PCOS but does not fulfill the JSOG 1993 criteria for PCOS. PMID- 17283380 TI - Hormone replacement therapy and vascular risk disorders in adult hypopituitarism. AB - Adult patients with hypopituitarism are treated by the replacement of deficient hormones, although GH has not been substituted until March 2006 in Japan except for clinical trial. This study examines which hormonal status influences the prevalence of vascular risk disorders in hypopituitary adults. A sample of 263 adult patients with hypopituitarism was studied, among whom there were various hormonal status such as no deficiency, treated or untreated deficiency of each pituitary hormone. Analysis of adult patients with hypopituitarism showed that hypertension was more prevalent in the older than in younger patients and in male than in female patients. Hypercholesterolemia and hypertriglyceridemia were more prevalent in patients with TSH deficiency even with thyroxine substitution than those without TSH deficiency. Both obesity and hypertension were less prevalent in patients with treated ACTH deficiency than those without ACTH deficiency. Obesity was more prevalent in patients with treated vasopressin deficiency than those without vasopressin deficiency. These results provide evidence that glucocorticoid substitution in ACTH deficient adults was favorable to prevent obesity and hypertension but that the thyroxine substitution in TSH deficient adults appeared rather insufficient to prevent hyperlipidemia. PMID- 17283382 TI - Construction of physical map and mapping of chromosomal virulence genes of the biovar 3 Agrobacterium (Rhizobium vitis) strain K-Ag-1. AB - Most plant pathogenic Agrobacterium strains have been classified into three biovars, "biovar 1 (A. tumefaciens; Rhizobium radiobacter), biovar 2 (A. rhizogenes; R. rhizogenes) and biovar 3 (A. vitis; R. vitis)". The bacteria possess diverse types of genomic organization depending on the biovar. Previous genomic physical maps indicated difference in location of rDNA and chromosomally coded virulence genes between biovar 1 and 2 genomes. In order to understand biovar 3 genome and its evolution in relation to the biovar 1, 2 and 3 genomes, we constructed physical map of a pathogenic biovar 3 strain K-Ag-1 in this study. Its genome consisted of two circular chromosomes (3.6 and 1.1 Mbp in length), and three plasmids (560, 230 and 70 kbp). Gene mapping based on the physical map showed presence of two rDNA loci in the larger chromosome and at least one rDNA locus in the smaller chromosome. Six chromosomal virulence genes, namely chvA, chvD, chvE, glgP, exoC and ros were found in the larger chromosome and not in the smaller chromosome. The location of rDNA loci is similar with that of biovar 1 genome, whereas the location of chromosomal virulence genes is similar with that of biovar 2 genome despite of the closer 16S-rRNA based phylogenetic relation of biovar 3 with biovar 1 than with biovar 2. Genomic PFGE RFLP analysis revealed that the K-Ag-1 strain, which was isolated on a kiwifruit plant in Japan, has the closest intra-species relation with two strains isolated from grapevine plants in Japan among eight biovar 3 strains examined. This datum suggests that the line of the strain is a major one in biovar 3 in Japan. Evolution of the genome of the strain is discussed based on the data. PMID- 17283383 TI - Plasticity of the domain structure in FlgJ, a bacterial protein involved in flagellar rod formation. AB - Bacterial flagellar rod structure is built across the peptidoglycan (PG) layer. A Salmonella enterica flagellar protein FlgJ is believed to consist of two functional domains, the N-terminal half acting as a scaffold or cap essential for rod assembly and the C-terminal half acting as a PG hydrolase (PGase) that makes a hole in the PG layer to facilitate rod penetration. In this study, molecular data analyses were conducted on FlgJ data sets sampled from a variety of bacterial species, and three types of FlgJ homologs were identified: (i) "canonical dual-domain" type found in beta- and gamma-proteobacteria that has a domain for one of the PGases, acetylmuramidase (Acm), at the C terminus, (ii) "non-canonical dual-domain" type found in the genus Desulfovibrio (delta proteobacteria) that bears a domain for another PGase, M23/M37-family peptidase (Pep), at the C terminus and (iii) "single-domain" type found in phylogenetically diverged lineages that lacks the Acm or Pep domain. FlgJ phylogeny, together with the domain architecture, suggested that the single-domain type was the original form of FlgJ and the canonical dual-domain type had evolved from the single domain type by fusion of the Acm domain to its C terminus in the common ancestor of beta- and gamma-proteobacteria. The non-canonical dual-domain type may have been formed by fusion of the Pep domain to the single-domain type in the ancestor of Desulfovibrio. In some lineages of gamma-proteobacteria, the Acm domain appeared to be lost secondarily from the dual-domain type FlgJ to yield again a single-domain type one. To rationalize the underlying mechanism that gave rise to the two different types of dual-domain FlgJ homologs, we propose a model assuming the lineage-specific co-option of flagellum-specific PGase from diverged housekeeping PGases in bacteria. PMID- 17283384 TI - Isolation of thermotolerant mutants by using proofreading-deficient DNA polymerase delta as an effective mutator in Saccharomyces cerevisiae. AB - Eukaryotic DNA polymerases delta and epsilon, both of which are required for chromosomal DNA replication, contain proofreading 3'-->5'exonuclease activity. DNA polymerases lacking proofreading activity act as strong mutators. Here we report isolation of thermotolerant mutants by using a proofreading-deficient DNA polymerase delta variant encoded by pol3-01 in the yeast Saccharomyces cerevisiae. The parental pol3-01 strain grew only poorly at temperatures higher than 38 degrees C. By stepwise elevation of the incubation temperature, thermotolerant mutants that could proliferate at 40 degrees C were successfully obtained; however, no such mutants were isolated with the isogenic POL3 strain. The recessive hot1-1 mutation was defined by genetic analysis of a weak thermotolerant mutant. Strong thermotolerance to 40 degrees C was attained by multiple mutations, at least one of which was recessive. These results indicate that a proofreading-deficient DNA delta polymerase variant is an effective mutator for obtaining yeast mutants that have gained useful characteristics, such as the ability to proliferate in harsh environments. PMID- 17283385 TI - Analysis of paternal transmission of mitochondrial DNA in Drosophila. AB - It has previously been shown that paternal mitochondrial DNA (mtDNA) can be detected in later generations in Drosophila. To further analyze the paternal transmission of mtDNA, the progeny of two intraspecific and three interspecific crosses were examined in the frequency of the paternal transmission of mtDNA, using closely related species of the melanogaster species subgroup. Types of mtDNA in the progeny of the individual backcrosses of F(1) females were analyzed by selective amplification of paternal mtDNA. More than 100 F(1) females were examined for each backcross. The same type of mtDNA as that of the paternal mtDNA was detected in approximately 20-60% of the backcrosses. The present results indicate that paternal leakage occurs in the intraspecific crosses as well as in the interspecific crosses in Drosophila. PMID- 17283386 TI - Cardiovascular responses of Type A and Type B behavior patterns to visual stimulation during rest, stress and recovery. AB - Differences in the cardiovascular responses of individuals with behavior patterns of Type A and Type B were investigated during rest, stress, and recovery by visual stimulation. Thirty healthy undergraduate and graduate students (mean age: 22.18+/-1.44 years) were categorized as Type A (N=14), or Type B (N=16) based on the Kwansei Gakuin's daily life questionnaire. The cardiovascular reactivity of all participants was repetitively monitored for 6 sessions, with each session comprising 3 conditional phases, viz., resting, stress, and post-stress recovery. A gray screen was displayed during resting, displeasure-evoking images were displayed under the stress condition, and video clips of a forest or a control image (a gray screen) were displayed during the recovery condition. When participants were subjected to different stimuli on a 42-inch plasma television screen in each session, electrocardiograms (ECG), impedance cardiograms and the blood pressure (BP) of the respective participants were continuously monitored. According to the results, Type A indicated higher sympathetic reactivity than Type B during resting and under stress. As such, Type A indicated a shorter pre ejection period (PEP) level during resting and a greater cardiac output (CO) increase under stress than Type B. Furthermore, parasympathetic predominance and parasympathetic antagonism accompanying the enhanced sympathetic activity induced by the unpleasant stress images decreased heart rate (HR) in both Type A and Type B, although the decrease in Type A was relatively meager. Unlike previous studies, the present study demonstrated that Type A indicated more enhanced sympathetic reactivity than Type B in resting physiological arousal levels and visual stimulus-induced stress. PMID- 17283388 TI - The properties and interrelationships of various force-time parameters during maximal repeated rhythmic grip. AB - The purpose of this study was to examine the properties and interrelationships of various force-time parameters including the inflection point for the rate of decline in force during a maximal repeated rhythmic grip. Fifteen healthy males (age M=21.5, SD=2.1 yr, height M=172.4, SD=5.7 cm, body mass M=68.2, SD=9.2 kg) participated in this study. Subjects performed a maximal repeated rhythmic grip with maximal effort with a target frequency of 30 grip.min(-1) for 6 min. The force value decreased linearly and markedly until about 70% of maximal strength for about 55 s after the onset of a maximal repeated rhythmic grip, and then decreased moderately. Because all parameters showed fair or good correlations between 3 min and 6 min, they are considered to be able to sufficiently evaluate muscle endurance for 3 min instead of 6 min. However, there were significant differences between 3 min and 6 min in the integrated area, the final force, the rate of the decrement constant (k) fitting the force decreasing data to y=ae( kx)+b and the force of maximal difference between the force and a straight line from peak force to the final force. Their parameters may vary generally by the length of a steady state, namely, a measurement time. The final force value before finishing and the rate of the decrement constant (k) reflect the latter phase during a maximal repeated rhythmic grip. Although many parameters show relatively high mutual relationships, the rate constant (k) shows relatively low correlations with other parameters. We inferred that decreasing the time until 80% of maximal strength and the amount of the decrement force for the first 1 min reflect a linear decrease in the initial phase. PMID- 17283387 TI - Evidence for higher heritability of somatotype compared to body mass index in female twins. AB - The influence of genetics on human physique and obesity has been addressed by the literature. Evidence for heritability of anthropometric characteristics has been previously described, mainly for the body mass index (BMI). However, few studies have investigated the influence of genetics on the Heath-Carter somatotype. The aim of the present study was to assess the heritability of BMI and somatotype (endomorphy, mesomorphy, and ectomorphy) in a group of female monozygotic and dizygotic twins from childhood to early adulthood. A total of 28 females aged from 7 to 19 years old were studied. The group included 5 monozygotic and 9 dizygotic pairs of twins. The heritability was assessed by the twin method (h(2)). The anthropometric measures and somatotype were assessed using standard validated procedures. Significant differences between monozygotic and dizygotic pairs of twins were found for height, endomorphy, ectomorphy, and mesomorphy, and the heritability for these measures was high (h(2) between 0.88 and 0.97). No significant differences were found between monozygotic and dizygotic twins for weight, and the BMI and the heritability indexes were lower for these measures (respectively 0.42 and 0.52). The results of the present study have indicated that the somatotype may be more sensible to genetic influences than the BMI in females. PMID- 17283389 TI - New percentage body fat prediction equations for Japanese females. AB - Anthropometry is a simple and cost-efficient method for the assessment of body composition. However prediction equations to estimate body composition using anthropometry should be 'population-specific'. Most popular body composition prediction equations for Japanese females were proposed more than 40 years ago and there is some concern regarding their usefulness in Japanese females living today. The aim of this study was to compare percentage body fat (%BF) estimated from anthropometry and dual energy x-ray absorptiometry (DXA) to examine the applicability of commonly used prediction equations in young Japanese females. Body composition of 139 Japanese females aged between 18 and 27 years of age (BMI range: 15.1-29.1 kg/m(2)) was measured using whole-body DXA (Lunar DPX-LIQ) scans. From anthropometric measurements %BF was estimated using four equations developed from Japanese females. The results showed that the traditionally employed prediction equations for anthropometry significantly (p<0.01) underestimate %BF of young Japanese females and therefore are not valid for the precise estimation of body composition. New %BF prediction equations were proposed from the DXA and anthropometry results. Application of the proposed equations may assist in more accurate assessment of body fatness in Japanese females living today. PMID- 17283390 TI - A comparison of the point of deflection from linearity of heart rate and the ventilatory threshold in the determination of the anaerobic threshold in Indian boys. AB - The purpose of the study was to assess whether the point of deflection from linearity of heart rate (HRD) could be used as an alternative method to determine the ventilatory threshold (VT) in Indian (Bengali) boys that represents the determination of the anaerobic threshold (AT), and also to standardize an exercise test to be effective in eliciting AT in Indian (Bengali) boys by using HRD. Twenty six (26) boys with a mean age of 12.8 (+/-1.18) years performed a graded maximal exercise test on a treadmill to determine peak VO(2), HRD and VT. The mean peak VO(2), weight related peak VO(2), peak pulmonary ventilation, and peak heart rate of the boys were found to be 1.75 l/min, 47.1 ml/kg/min, 66.9 l/min and 200.2 beats/min respectively. There were no significant differences between mean VO(2), weight related VO(2), pulmonary ventilation (VE), heart rate and respiratory exchange ratio (RER) that were measured at VT and HRD. The mean VO(2) measured at VT and HRD was found to be 1.46 and 1.45 l/min, which were about 84% and 83% of their respective peak values. Linear regression analysis revealed a correlation of 0.94 (p<0.01) between VO(2) measured at VT and VO(2) measured at HRD, so the present study indicates that the point of deflection from linearity of heart rate (HRD) may be an accurate predictor of VT in most but not all boys. PMID- 17283392 TI - Bovine spongiform encephalopathy (BSE) safety measures in Japan. AB - Since the first identification of bovine spongiform encephalopathy (BSE) in Japan in September 2001, a series of safety measures was introduced by the Ministry of Agriculture, Forestry and Fisheries, the Ministry of Health, Labour and Welfare and the Food Safety Commission of the Cabinet Office. These measures included blanket BSE testing and removal of specified risk materials at slaughterhouses, surveillance of risk animals and a ban on the use of meat-and-bone meals and traceability on all farms. The Japanese experience over the past five years has shed light on several issues in countries that have a low BSE incidence. PMID- 17283391 TI - Inhibition of heart rate variability during sleep in humans by 6700 K pre-sleep light exposure. AB - Two different spectral analyses of heart rate (HR) variability (HRV) were performed on seven young male subjects to evaluate the effects of different color temperatures of light exposure (6700 K, 5000 K, 3000 K) before sleep on cardiac vagal activity. In investigating HRV, we used an ordinary fast Fourier transform (FFT) and coarse graining spectral analysis (CGSA), which selectively extracts random fractal components from a given time series. The results showed that suppressions of HR during sleep after 6700 K light exposure were more inhibited than the other two lighting conditions. Increases in high-frequency (HF) components of HRV during sleep were also inhibited by 6700 K pre-sleep lighting. These results indicate that pre-sleep exposure to light of a higher color temperature may inhibit the enhancement of cardiac vagal activity during sleep. Moreover, significant HF alterations were shown in fractal-free HF (not in ordinary HF) components by CGSA. Because the HF component originates from respiratory sinus arrhythmia with periodical fluctuations, CGSA may be an appropriate approach for HRV evaluation during sleep. PMID- 17283393 TI - Anesthetic and cardiopulmonary effects of total intravenous anesthesia using a midazolam, ketamine and medetomidine drug combination in horses. AB - The anesthetic and cardiopulmonary effects of midazolam, ketamine and medetomidine for total intravenous anesthesia (MKM-TIVA) were evaluated in 14 horses. Horses were administered medetomidine 5 microg/kg intravenously as pre anesthetic medication and anesthetized with an intravenous injection of ketamine 2.5 mg/kg and midazolam 0.04 mg/kg followed by the infusion of MKM-drug combination (midazolam 0.8 mg/ml-ketamine 40 mg/ml-medetomidine 0.1 mg/ml). Nine stallions (3 thoroughbred and 6 draft horses) were castrated during infusion of MKM-drug combination. The average duration of anesthesia was 38 +/- 8 min and infusion rate of MKM-drug combination was 0.091 +/- 0.021 ml/kg/hr. Time to standing after discontinuing MKM-TIVA was 33 +/- 13 min. The quality of recovery from anesthesia was satisfactory in 3 horses and good in 6 horses. An additional 5 healthy thoroughbred horses were anesthetized with MKM- TIVA in order to assess cardiopulmonary effects. These 5 horses were anesthetized for 60 min and administered MKM-drug combination at 0.1 ml/kg/hr. Cardiac output and cardiac index decreased to 70-80%, stroke volume increased to 110% and systemic vascular resistance increased to 130% of baseline value. The partial pressure of arterial blood carbon dioxide was maintained at approximately 50 mmHg while the arterial partial pressure of oxygen pressure decreased to 50-60 mmHg. MKM-TIVA provides clinically acceptable general anesthesia with mild cardiopulmonary depression in horses. Inspired air should be supplemented with oxygen to prevent hypoxemia during MKM-TIVA. PMID- 17283394 TI - In vitro and in vivo effects of recombinant bovine interferon-tau on bovine leukemia virus. AB - The antiviral effects of recombinant bovine interferon-tau (rboIFN-tau) on bovine leukemia virus (BLV) were examined in vitro and in vivo. In the in vitro experiments, BLV titers decreased in FLK-BLV cells and in peripheral blood mononuclear cells of BLV-infected cattle treated with rboIFN-tau at a concentration higher than 10(2) U/ml. In order to examine the in vivo effects of rboIFN-tau, 10 BLV-infected cattle were subcutaneously injected with rboIFN-tau. In the first experiment, 6 cows were administrated with 10(5) U/kg body weight of rboIFN-tau 3 times per week for 4 weeks, while in the second experiment 4 cows were administrated with 10(6) U/kg body weight of rboIFN-tau 3 times per week for 3 weeks. No adverse effects were observed after the administration of rboIFN-tau. In experiment No. 1, the mean BLV titers in cattle decreased in the post-rboIFN tau administration period compared to the pre-rboIFN-tau administration period. In experiment No. 2, the mean BLV titers in cattle decreased in the rboIFN-tau administration period. These results suggest that rboIFN-tau decreases BLV titers in vitro and in vivo and that rboIFN-tau possibly reduces the degree of BLV titer in cattle without severe side effects. PMID- 17283395 TI - Ethanol exposure suppresses survival kinases activation in adult rat testes. AB - The present study was designed to evaluate whether ethanol suppresses survival signaling pathways in rat testes. Ethanol (1.5 g/kg or 3 g/kg i.p., 15% v/v in saline) was administrated to adult male rats for 10 days. Ethanol treatment significantly increased the number of TUNEL-positive cells in rat testes. Potential activation was measured by phosphorylation of Akt and Erk1/2 using Western blot analysis. Ethanol decreased the levels of activated survival kinases, pAkt and pErk1/2. The phosphorylation of Bad at Ser112 and Ser136 was decreased in ethanol-treated animals in comparison to saline-treated animals. Moreover, the interaction of pBad with 14-3-3 was decreased by ethanol exposure. In conclusion, our findings suggest that ethanol induces apoptotic cell death by suppressing the activation of survival kinases and the phosphorylation of their downstream targets in rat testes. PMID- 17283396 TI - Survival change of ventral mesencephalon-derived progenitor cells after grafting into unilateral intact adult rat striatum. AB - Neural transplantation is one of the most promising treatments for neurodegenerative disorders. Survival rates of embryonic dopamine (DA) neurons following transplantation are low, between 2% and 20% in a number of animal models. To further establish survival changes of the transplanted gestational day 13.5 ventral mesencephalic (VM) cells into left intact adult rat striata so that design strategies of increasing survival of DA neurons, the tyrosine hydroxylase (TH) expression of VM-derived progenitor cells has been examined using immunohistochemistry and Western blot analysis. TH immunostaining revealed that the grafted VM cells developed to mature TH-positive neurons strongly at 3 weeks, peaked at 4 weeks, thereafter, gradually dropped following the degenerative expression of the grafted cells at both 5 and 6 weeks after transplantation. Western blot analysis also showed that the TH proteins were maximally expressed at 4 weeks post-grafting. Our finding suggested that the peak of surviving VM derived TH positive cells occurred approximately 4 weeks after transplantation. PMID- 17283397 TI - Fluid and electrolyte shifts during and after Agility competitions in dogs. AB - This research assesses the relative contribution of splenic contraction and fluid shifts out of the vascular compartment to the increases in packed cell volume associated with Agility exercises. It also aims to evaluate the changes in the concentrations of electrolytes and markers of hydration state. Fifteen dogs of both sexes were subjected to an Agility exercise of an approximate duration of 100 s. Blood samples were obtained within the first 30 s after competition and at 5, 15, and 30 min of recuperation. Resting values were established previously. The following parameters were determined: packed cell volume (PCV), plasma lactate (LA), total plasma protein (TPP), albumin (ALB), urea (BUN), creatinine (CREA), chloride (Cl), calcium (Ca), phosphorus (P), sodium (Na) and potassium (K). Changes in plasma volume (PV), total RBC volume (V(RBC)) and blood volume (BV) were calculated immediately after exercise and at 30 minutes of recovery. It was found that during Agility competition, BV, V(RBC) and PV increased 12, 21 and 4% respectively, indicating that the spleen contraction was the main determinant on the increase of BV. In comparison with resting values, BV decreased after recuperation (-5%), due to the recapture of erythrocytes by the splenic reserve (V(RBC), -12%). Additionally, Agility exercise induced increases in plasma Cl and LA, with significant reductions of ALB, Ca and P and absence of modifications in Na, K, BUN and CREA concentrations. PMID- 17283398 TI - Neural differentiation of human neuroblastoma GOTO cells via a Rho-Rho kinase phosphorylation signal transduction and continuous observation of a single GOTO cell during differentiation. AB - Nerve growth factor, retinoic acid, dibutyryl cAMP, ganglioside G(Q1b), and botulinum C3 exoenzyme were evaluated for their neural differentiating potential on human neuroblastoma GOTO cells. C3 exoenzyme is an ADP-ribosyltransferase inactivating Rho protein (a small GTP-binding protein). C3 exoenzyme caused the fastest differentiation of GOTO cells into neural cells and induced the strongest network of the cells. Fasudil, an inhibitor of Rho-kinase, induced outgrowth of the neurites in the GOTO cells. Calyculin A, an inhibitor of phosphatases including myosin phosphatase, counteracted C3 exoenzyme-induced neurite outgrowth of the cells. These findings suggest that differentiation of GOTO cells triggered by C3 exoenzyme is attained via inactivation of Rho protein, inhibition of Rho kinase, and activation of myosin phosphatase. Because of the strong differentiating potential of C3 exoenzyme, the transduction pathway consisting of Rho protein, Rho-kinase, and myosin phosphatase seems to be main stream in the neural differentiation of GOTO cells. A single GOTO cell was observed continuously after treatment with C3 exoenzyme. The cell started to change shape from its original morphology only 15 min after treatment with C3 exoenzyme, and it was completely spherical within 60 min. Neurites appeared on the membrane of the cell 2 hr after the treatment and then gradual outgrowth began. These observations are fundamental information in elucidating the mechanism of neural differentiation, especially at an early stage. PMID- 17283399 TI - Minimally invasive determination of cardiac output by transthoracic bioimpedance, partial carbon dioxide rebreathing, and transesophageal Doppler echocardiography in beagle dogs. AB - Minimally invasive cardiac output was determined using transthoracic bioimpedance (BICO), partial carbon dioxide rebreathing (NICO) and transesophageal Doppler echocardiography (TEECO) and compared to thermodilution (TDCO) in 6 beagle dogs. The dogs were 2 years old, weigh between 9.1-13.0 kg and were anesthetized with nitrous oxide-oxygen-sevoflurane. All dogs were administered a neuromuscular blocking drug and artificially ventilated during anesthesia. Thirty paired measurements of TDCO and each non-invasive method were collected during low, intermediate, and high values of cardiac output achieved by varying the depth of anesthesia and the administration of dobutamine. Cardiac output values ranged from 1.10-2.50 L/min for BICO compared to 0.81-4.88 L/min for TDCO; 0.70-2.60 L/min for NICO compared to 0.89-4.45 L/min for TDCO; and 0.59-4.37 L/min for TEECO compared to 0.57-4.15 L/min for TDCO. The limits of agreement and percentage error were -0.58 +/- 1.56 L/min and +/- 75.4% for BICO, -1.04 +/- 1.08 L/min and +/- 56.0% for NICO, and 0.03 +/- 0.26 L/min and +/- 12.3% for TEECO compared to TDCO. In conclusion, TEECO provided the best agreement to TDCO in sevoflurane anesthetized beagle dogs. PMID- 17283400 TI - Effect of ovary lipid of skipjack tuna on rat serum components after stress application. AB - Lipid extracted from the ovary of skipjack tuna by the method that we developed is rich in phospholipid-type docosahexaenoic acid. The ovary lipid of skipjack tuna (OLS) was studied for its anti-stress activity in male Wistar rats, focusing on stress-related blood components: recovery from stress was examined after application of water immersion restraint stress. As a result, serum corticosterone (CORT) secretion was inhibited and decreased rapidly after stress application in rats given OLS compared with control rats. As CORT acts as a glucocorticoid, non-esterified fatty acid (NEFA) is expected to increase by stress application. However, the concentration tended to be lower in rats given OLS than in control rats. With respect to OLS concentration, OLS increased serum dehydroepiandrosterone, secretion concentration-dependently. In addition, as with the recovery study, it tended to inhibit the increase in NEFA. These results indicate that OLS may have an anti-stress activity against acute stress. PMID- 17283401 TI - Phylogenetic comparison of Leucocytozoon spp. from wild birds of Japan. AB - Eight species of Japanese birds were found to be infected with Leucocytozoon species using microscopic analysis. We used PCR and sequence analysis of the mitochondrial cytochrome b gene (cyt b) to compare the genetic background among these detected protozoa species. In 20 individuals of 22 samples, a single amplified band was detected from 6 of 8 bird species; 9 Japanese rock ptarmigans (Lagopus mutus japonicus), 4 large-billed crows (Corvus macrorhynchos), 2 carrion crows (C. corone), 2 scops owls (Otus scops), 1 Japanese grosbeak (Eophona personata), and 2 brown-eared bulbuls (Hypsipetes amaurotis), respectively. Phylogenetic analysis based on the partial cyt b sequences revealed that all Leucocytozoon isolates in Japan closely grouped with other Leucocytozoon species previously reported in the literature. Among the Japanese isolates, the phylogenetic tree suggested that L. lovati from the Japanese rock ptarmigan may be basal to the parasites found in other bird species. Our study is the first to identify the molecular relationships among Leucocytozoon parasites in the avifauna of Japan. PMID- 17283402 TI - Functional thyroid gland adenoma in a dog treated with surgical excision alone. AB - An 11-year-old male Golden Retriever presented with progressive weight loss, tachycardia, hyperthermia, polyuria and polydipsia. A freely movable mass, 4.5 x 4 cm in size, was palpated at the cranioventral cervical region. Hormonal study revealed high levels of serum thyroid hormones, and a tentative diagnosis of hyperthyroidism due to a thyroid tumor was made. The tumor was removed surgically and diagnosed histopathologically as thyroid gland adenoma. Serum thyroid hormone levels decreased after surgery with improved clinical signs. At 12 months after surgery, the dog maintained a good physical condition with no evidence of recurrence. PMID- 17283403 TI - Maxillofacial rhabdomyosarcoma in the canine maxillofacial area. AB - Three dogs had a diagnosis of maxillofacial rhabdomyosarcoma. These dogs were treated with surgery and/or radiotherapy, and had poor clinical responses. The tumor tissues in all three cases were observed around the upper premolar teeth with ulcerative lesions and CT examinations in each case revealed extensive bony involvement into the maxilla. Two cases were subjected to surgical excision of the tissues, followed by an external radiation therapy. The other case was only treated with palliative radiation. Outcomes of the treatment of all the cases were quite poor because of the invasive and refractory nature of the tumor cells, leading to the local recurrence and lung metastasis early in the clinical course. All dogs died within two months of the first admission. PMID- 17283404 TI - Insulin and glucagon secretory patterns during propionate and arginine tolerance tests in Japanese black cattle with growth retardation. AB - To evaluate the energy condition of cattle with growth retardation, propionate (PTT) and arginine tolerance tests (ATT) were carried out. The insulin/glucagon concentration ratio immediately before PTT or ATT in the cattle with growth retardation was lower than in the control. In the growth-retarded cattle, insulin AUC(0-120 min) during PTT was lower than in the control, while glucagon-AUC(0-120 min) was the same as in the control. Insulin-AUC(0-120 min) during ATT in the cattle with growth retardation tended to be lower than in the control, whereas glucagon-AUC(0-120 min) was the same. Therefore, insulin-AUC(0-120 min)/glucagon AUC(0-120 min) in the cattle with growth retardation was lower than in the control during both tolerance tests. The growth-retarded cattle showed lower insulin/glucagon ratio similar to that found in starved and lactating cattle, suggesting a lack of energy. PMID- 17283406 TI - Clinical significance of circulating vascular endothelial growth factor in dogs with mammary gland tumors. AB - Increase in circulating vascular endothelial growth factor (VEGF) is suggested as a prognostic indicator in human patients with malignant tumors. The purpose of this study was to evaluate the clinical significance of circulating VEGF in dogs with mammary gland tumors (MGT). Both plasma and serum VEGF were significantly higher in dogs with MGT when compared with those in the healthy dogs. In dogs with MGT, the plasma and serum VEGF of the malignant group increased significantly compared with those of the benign group. Additionally, there was a significant difference between the plasma and serum VEGF in the groups with postoperative metastasis and no metastasis. Circulating VEGF is expected to be clinically available for the determination of prognosis in canine MGT. PMID- 17283405 TI - Pentalogy of Fallot in a Korean Sapsaree dog. AB - A 5-month-old female Korean Sapsaree dog was presented with severe ascites, cyanosis, respiratory difficulty and exercise intolerance. Diagnostic imaging studies revealed a dextropositioned and over-riding aorta, pulmonary valvular stenosis, ventricular and atrial septal defects, and right ventricular hypertrophy. Based on these findings, the dog was diagnosed as a case of tetralogy of Fallot with atrial septal defect (pentalogy of Fallot). The dog was medically managed by use of diuretics and vasodilators and an occasional phlebotomy. PMID- 17283407 TI - Molecular cloning of a cDNA encoding the feline CD62L. AB - We cloned a cDNA fragment encoding a feline homologue of L-selectin (CD62L). The extracellular region of the feline CD62L fragment contained a calcium-dependent (C-type) lectin domain, an epidermal growth factor-like domain, and two Sushi/CCP/SCR domains. The flow cytometric analysis confirmed that the feline CD62L molecule, which was expressed 293T cells, retained an epitope recognized by an anti-human CD62L monoclonal antibody (Leu-8). PMID- 17283408 TI - Molecular cloning of two caspase-like genes from the hard tick Haemaphysalis longicornis. AB - We identified two caspase-like genes from the midgut cDNA library of the hard tick, Haemaphysalis longicornis. Sequence analysis showed that these cDNAs encoded homologues of caspase-2 and caspase-8 that were categorized as apoptosis initiators. The H. longicornis caspase-2 (Hlcaspase-2) cDNA encodes 340 amino acid residues with a predicted molecular weight (Mw) of 38.5 kDa. Another cDNA identified as the H. longicornis caspase-8 (Hlcaspase-8) encodes 306 amino acid residues with an estimated Mw of 35.3 kDa. A catalytic active site was highly conserved in Hlcaspase-8 but not in Hlcaspase-2. RT-PCR analysis showed that both Hlcaspase-2 and Hlcaspase-8 were expressed in tick midgut and salivary glands. This is the first report of the molecular cloning of apoptosis-related genes in the tick. PMID- 17283409 TI - Pancreatic acinar cell carcinoma with intracranial metastasis in a dog. AB - This report concerns a case of pancreatic carcinoma with widespread metastases to many organs including intracranial metastasis. An eleven-year-old, male, mixed breed dog showed emaciation, ataxia, and multiple visible tumors within the neck. A MRI examination of the patient was conducted because of ataxia, and it was found that the intracranial invasive growth had resulted in compression of the brain stem. Necropsy was performed after the patient died. Based on gross and microscopic examination, the primary tumor cells were located in the left lobe of the pancreas and widespread metastasis was found into various organs, including the brain, lungs, liver, kidneys, tonsils, serosal surface of the esophagus, and submandibular, pulmonary hilar, mediastinal, and mesenteric lymph nodes. This case indicates that pancreatic adenocarcinoma should be included in the differential diagnosis list when cervical neck masses are detected. PMID- 17283410 TI - [Basic strategies on first- and second-line chemotherapy for advanced gastric cancers]. PMID- 17283411 TI - [Up to date chemotherapy for colon cancer]. PMID- 17283412 TI - [Clinical development of chemotherapy for advanced gastric cancer]. PMID- 17283413 TI - [Transcatheter embolization of an inferior mesenteric arteriovenous fistula with frequent mucous diarrhea]. AB - We report a case of inferior mesenteric arteriovenous fistula without portal hypertension or mesenteric ischemia. A 64-year-old man had developed frequent mucous diarrhea during the previous month. Colonoscopy showed highly edematous mucosa of the rectum. Barium enema demonstrated localized stricture of the same part but no evidence of malignancy. Finally we established a diagnosis by 3D-CT and selective abdominal angiography. Transcatheter arterial embolization was successfully performed. After that, his symptoms gradually improved as all abnormal findings on colonoscopy, barium enema and abdominal CT disappeared. PMID- 17283414 TI - [A case of colonic obstruction due to post-operative stenosis of the colon and multiple enteroliths]. AB - An 81-year-old man who had under gone two abdominal surgeries and temporary colostomy 30 years previously was admitted due to lower abdominal pain and vomiting. An abdominal X-ray film and abdominal CT scan showed intestinal distension and multiple calcareous deposits in the colon. Gastrografin enema examination revealed smooth stenosis at the sigmoid colon and many additional defects. Endoscopy could not be performed due to the stenosis. He did not agree to surgery. Seven months later, he was admitted again, due to colonic obstruction. Surgery was performed which revealed colonic obstruction as the source of post-operative stenosis of the sigmoid colon and multiple enteroliths. The stones consisted of a core and a hull and contained ammonium magnesium phosphate. PMID- 17283415 TI - [Treatment by danaparoid sodium for portal venous thrombosis]. AB - We report a case of hepatitis B type liver cirrhosis with portal venous thrombosis in which danaparoid sodium was very effective. The portal venous thrombosis in this case disappeared 2 weeks commencing after administration of danaparoid sodium. The patient had not adverse effects or complications such as hemorrhage, and the clinical course was good. We consider that danaparoid sodium is an anticoagulant unlikely to cause adverse effects such as hemorrhage, and that it might be effective for treatment of portal venous thrombosis. We intend to examine the indications of treatment with danaparoid sodium, clarify the best administration method, and establishment of maintenance therapy by investigating more cases. PMID- 17283416 TI - [Clonorchiasis complicated with duodenal papillary cancer in a visitor from China]. AB - It is well known that long-term infection with Clonorchis sinensis often causes bile duct cancer, usually. It occurs in the intrahepatic bile duct. We encountered a rare case of clonorchiasis complicated with duodenal papillary cancer. The patient was a woman from China. Although clonorchiasis is rarely found in Japan, the promotion of international exchange may increase the number of visitors from endemic areas. Thus we must pay sufficient attention to this disease. Also, we reported that the microplate ELISA technique was useful in the diagnosis of clonorchiasis with high accuracy in this case. PMID- 17283417 TI - [A case of fulminant hepatitis E treated with artificial liver support]. AB - A 40-year-old man, who had suffered from general malaise and brown urine during his stay in China, was admitted with remarkable jaundice and hepatocellular disorders soon after he returned to Japan. Because his coagulation test results worsened, he was transferred to our hospital. No evidence of hepatitis A-D virus infection, autoimmune hepatitis, or metabolic disorders was noticed. His prothrombin time was extended (18%), grade II encephalopathy appeared on the second hospital day, and fulminant hepatitis was diagnosed. Artificial liver support was introduced, and his hepatic coma and coagulation parameters gradually recovered. Genotype IV hepatitis E virus RNA was detected in his early phase sera and also both IgG and IgM type anti-hepatitis E virus antibodies were detected. Fulminant hepatitis E resulting from infection in China was diagnosed. PMID- 17283418 TI - [A case of superficial bile duct carcinoma showing extensive intraductal spread without bile duct stenosis, diagnosed by intraductal ultrasonography]. AB - We report a case of superficial bile duct carcinoma showing extensive intraductal spread without dilatation of the bile duct in which diagnosis was established preoperatively by transpapillary forceps biopsy and intraductal ultrasonography. A 78-year-old man was given a diagnosis of acute cholecystitis, and percutaneous transhepatic gallbladder drainage (PTGBD) was performed. Cholangiography via the PTGBD tube revealed a tiny irregularity in the hilar bile duct. Transpapillary intraductal ultrasonography showed that this irregularity extended from the intrahepatic bile duct to the middle of the bile duct. Bile duct biopsy revealed malignancy, and thus bile duct resection and hepaticojejunostomy were performed. Histological examination verified a well-differentiated adenocarcinoma confined to the epithelium and the fibromuscular layer. PMID- 17283419 TI - [A case of granulocyte-colony stimulating factor producing ductal adenocarcinoma of the pancreas]. AB - We report a case of pancreatic ductal adenocarcinoma producing granulocyte-colony stimulating factor (G-CSF). A 56-year-old Japanese man was admitted to our hospital with back pain and high fever. An abdominal CT scan revealed masses in the pancreatic body to the tail, and both lobes of the liver. A biopsy specimen of the hepatic tumor demonstrated metastatic poorly differentiated adenocarcinoma. We administered oral S-1 in combination with gemcitabine. However, his general condition gradually worsened, and a high serum level of G CSF persisted. He died 135 days after admission. The diagnosis of autopsy was pancreatic ductal adenocarcinoma. Immunohistochemical staining showed the presence of G-CSF in tumor cells. The final diagnosis was G-CSF-producing pancreatic carcinoma. PMID- 17283420 TI - [A case of Castlemans disease (plasma cell type) in which autoimmune pancreatitis developed 6 years later]. AB - In 1998 a 74-year-old man, he had a medical checkup and mediastinal and hilar lymph node hyperplasia were discovered. Since the lymph nodes showed a tendency to increase in size, mediastinal lymph node biopsy was performed in the following year. Castlemans disease was diagnosed, and he was followed up. In 2005, autoimmune pancreatitis (AIP) developed. At this time, the mediastinal lymph node that had been biopsied was stained with anti-IgG4 antibody. Further examinations on pancreatic lesions associated with Castlemans disease and AIP are necessary in relation to IgG4-related systemic diseases. PMID- 17283422 TI - Huge expanding haematoma of the thoracic wall after thoracocentesis in a 75-year old man with myelodysplastic syndrome. PMID- 17283421 TI - [Preliminary study of the efficacy of 12 weeks treatment with consensus interferon in patients with chronic hepatitis C infected with serogroup 2 and low pretreatment viremia]. PMID- 17283423 TI - Interaction between C-reactive protein and endothelin-1 in coronary artery disease. AB - BACKGROUND: Increased concentrations of serum C-reactive protein (CRP) have been reported to predict major cardiovascular events in patients with coronary artery disease (CAD). Increased concentrations of endothelin-1 (ET-1) are also associated with poor prognosis after myocardial infarction. HYPOTHESIS: We tested the hypothesis that ET-1 might contribute to CRP in prediction of adverse outcome in CAD. METHODS: Serum high sensitive CRP and plasma ET-1 levels of 40 patients who have stable CAD and 25 control subjects were measured, and correlation analysis between these molecules was performed. RESULTS: Mean high sensitive CRP was 8.64 +/- 12.73 mg/l, and mean ET-1 was 8.24 +/- 7.06 pg/ml in the CAD group. We found that there was no statistically significant correlation between high sensitive CRP and ET-1 in either CAD group (p = 0.82), or the control group (p = 0.85). In a subgroup of 13 patients who were not under statin treatment, we found a strong correlation between the levels of these molecules (p = 0.01). CONCLUSION: Our study does not clearly support or exclude a link between CRP and ET-1 in patients who have stable CAD. PMID- 17283425 TI - Plasma homocysteine levels and late outcome in patients with unstable angina. AB - AIM OF THE STUDY: Previous studies have suggested that total plasma homocysteine (HCY) is an important cardiovascular risk factor because of its interaction with vascular smooth muscle cells, endothelium function, plasma lipoprotein, coagulation factors and platelets. The aim of this study was to evaluate a possible relationship between HCY levels and the severity of coronary artery disease (CAD) and its prognostic value in patients with unstable angina (UA). METHODS AND RESULTS: Ninety-four patients with UA were recruited and underwent coronary angiography and in some cases myocardial revascularization. The primary end point was the severity of CAD. The clinical end points were the recurrence of UA and the compositive end point of the occurrence of cardiac death and re hospitalization due to acute coronary syndrome. HCY levels were shown to be poorly correlated with the severity of CAD. After 48 months' of follow-up, a graded relationship between HCY levels and recurrence of UA and compositive end point was found (p < 0.001). CONCLUSIONS: In the light of events occurring during the follow-up period, it was concluded that total plasma HCY is a strong predictor of recurrence of UA. PMID- 17283424 TI - C-reactive protein distribution and correlates among men and women with chronic coronary heart disease. AB - BACKGROUND: C-reactive protein (CRP) elevated in inflammation is associated with atherosclerotic disease. We describe the distribution of CRP and its association with coronary heart disease (CHD) risk factors in a large CHD patient group. METHODS: This analysis comprises 2,723 male and 256 female CHD patients, included in the Bezafibrate Infarction Prevention (BIP) study. High sensitive CRP levels were determined in frozen plasma samples. RESULTS: CRP distribution, was normalized upon log transformation. Levels among women were higher than in men in the entire group (4.4 vs. 3.5 mg/l) and in each age group. Co-morbidities, smoking, lower education level, and use of cardiovascular drugs, were associated with elevated CRP levels in both sexes. The correlation between CRP and body mass index (BMI), insulin and glucose was stronger among women. The explained variability in CRP level was larger in women (20%) compared to men (13%). Among women, BMI explained 10% of CRP variability, whereas the contribution of each variable among men was significantly smaller. CONCLUSIONS: Among men and women with CHD, CRP level was correlated with traditional risk factors and to a lesser degree to manifestation of CHD. BMI is the main contributor to CRP variability, explained by these factors among women. PMID- 17283426 TI - Very late in-stent restenosis in a bare metal stent. AB - Restenosis after coronary artery stenting is a common phenomenon and represents a topic of great interest. Although a great volume of research is referring to restenosis, still many issues are not fully understood by the cardiological community. Here we present a case of very late restenosis, after a bare metal stent implantation. PMID- 17283427 TI - Morphologic substrates for first-branch pulmonary arterial hypoplasia in transposition of the great arteries. AB - BACKGROUND: Distal right-sided outflow obstruction remains a problem after arterial switch operation. We studied the anatomical features of the pulmonary trunk (PT) and its branches that are susceptible to right and left pulmonary arterial (RPA and LPA) hypoplasia in transposition of the great arteries (TGA). METHODS: One hundred and one angiograms of TGA performed between 1981 and 1996 were viewed, and Polaroid photos were taken at end-systole. The diameters of RPA, LPA, PT, duct, ascending aorta, and angles between PA and PT were measured, and the ductal flow direction was recorded. RESULTS: Forty-eight cases (47.5%) had a PA/PT diameter ratio (both PAs had same size) below 0.49. A smaller PA/PT was significantly related to posterior inclination of the proximal PT [narrower right (r = 0.50, p < 0.00001) and left (r = 0.48, p < 0.00001) PA-PT angle in lateral view] and a larger duct (r = 0.37, p < 0.0001). Eighteen patients had a follow-up angiogram after a mean period of 8.5 months. Those with a closed duct had evident PA growth (n = 12, 0.51 +/- 0.09 to 0.74 +/- 0.17, p < 0.0001), but four patients with an attenuated duct had no significant change (0.58 +/- 0.06 to 0.68 +/- 0.08, p = NS), and one with a persistent large duct had even regression of PA/PT (0.36-0.19). The direction of ductal flow was toward the aorta during early systole on cineangiogram. CONCLUSIONS: First-branch PA hypoplasia, which is frequently seen in TGA, was related to the right-to-left shunt through a duct resulting in hemodynamic starvation, and to posterior inclination of the proximal PT in this setting. Natural regression of the duct facilitated PA growth. PMID- 17283428 TI - 'Syringe-in-the-pocket'--a new approach to the outpatient thromboembolic prophylaxis of recurrent atrial fibrillation. AB - Chronic anti-coagulation is not an attractive prospect to patients with atrial fibrillation (AF) after successful restoration of sinus rhythm. We researched the feasibility of self-screening for AF performed by instructed patients and, where necessary, prompt self-administration of an initial dose of low-molecular weight heparin (LMWH) prior to seeking medical attention. MATERIALS AND METHODS: Persistent AF qualified to elective cardioversion was our focus. Two hundred and sixty-three consecutive patients (M/F: 179/84, mean age: 59.8 +/- 8.6) were followed for a mean of 2.6 +/- 1.7 years. All patients were trained to identify AF by palpation of the radial pulse and to self-inject LMWH in the case of arrhythmia recurrence. Two hundred and thirty-two patients who correctly recognized AF recurrence and those without episodes of AF during 4 weeks after cardioversion were equipped with nadroparine after acenocoumarol discontinuation. In 191 patients AF recurred during further observation, 172 of them correctly identified AF episodes, including 162 who performed LMWH injections at home. Seven patients who had performed LMWH injections presented with sinus rhythm on arrival to hospital, six patients had AF. Two out of 21 patients who failed to identify their AF episodes and one patient of those who correctly detected the AF recurrence, but failed to perform LMWH self-injection suffered from ischemic stroke (sensitivity 96.1%, specificity 60.4%). No side effects of domiciliary LMWH self-injection were identified. CONCLUSION: When properly trained, the majority of patients can accurately diagnose AF recurrence and self-inject an initial dose of LMWH, which makes it a feasible and potentially attractive anti thromboembolic strategy. PMID- 17283429 TI - Open-heart surgery in patients with liver cirrhosis: indications, risk factors, and clinical outcomes. AB - BACKGROUND: Because of recent advances in cardiopulmonary bypass (CPB) surgery, there are broadened indications to approach patients with a high operative risk. Meanwhile, there is an increasing number of patients with severe liver dysfunction subjected to open-heart surgery. This retrospective study was designed to evaluate the operative indications and clinical outcomes in patients with liver cirrhosis (LC) undergoing open-heart surgery. In addition, determinants influencing their prognosis were assessed. PATIENTS AND METHODS: Between May 1996 and June 2005, 24 patients with LC underwent CPB open-heart surgery in our institution. The preoperative severity of the LC was determined according to the Child-Pugh classification. Their perioperative data were analyzed. Several perioperative factors were compared by multivariate logistic regression analysis between survivors and nonsurvivors to determine possible risk factors contributing to mortality. RESULTS: There were 14 females and 10 males. Their age ranged from 36 to 72 (mean 53 +/- 13) years. Seventeen cases were classified as having Child-Pugh class A LC, 6 as having Child-Pugh class B, and 1 as having Child-Pugh class C LC. All patients underwent CPB surgery. The mean operation time and the cross-clamp time were 160 +/- 53 and 90 +/- 42 min, respectively. During the first 24 h after the operation, the mean chest tube output was 1,080 +/- 320 ml. The mean duration of mechanical ventilation was 32 +/- 22 h, and the mean intensive care unit stay was 11 +/- 8 days. Sixty-six percent of the patients experienced significant morbidity. Fifty-three percent of the patients with Child-Pugh class A LC and 100% of those with Child-Pugh class B and C LC suffered postoperative complications. The overall mortality rate was 25%. The postoperative mortality rates of the patients with Child-Pugh class A, B, and C LC were 6, 67, and 100%, respectively. Preoperative serum total bilirubin and cholinesterase levels and EuroSCORE (European System for Cardiac Operative Risk Evaluation) values along with CPB time were identified as the important predictors to differentiate between survivors and nonsurvivors by multivariate logistic regression analysis. CONCLUSIONS: The Child-Pugh class is associated with hepatic decompensation and mortality after open-heart CPB surgery in patients with LC. Such surgery can be performed safely in patients with a Child-Pugh class A LC. But cardiac interventions using CPB in patients with more advanced LC are associated with high mortality and morbidity rates. The preoperative total plasma bilirubin and cholinesterase concentrations as well as the EuroSCORE along with the CPB time are identified as statistically significant predictors of mortality after open-heart surgery in patients with LC. Our findings indicate that patients with chronic liver disease scheduled for open heart surgery should be carefully evaluated before the operation and that the CPB duration should be as short as possible. PMID- 17283430 TI - Improved neovascularization of PEGT/PBT copolymer matrices in response to surface modification by biomimetic coating. AB - PEGT/PBT (polyethylene glycol terephthalate/polybutylene terephthalate) copolymer matrices with three different surface coatings [calcium-phosphate (Ca-P), collagen, and gas plasma] were placed into dorsal skinfold chambers of 24 balb/c mice. Untreated PEGT/PBT matrices served as the controls. The basal surfaces of the implants directly contacted the striated skin muscle. Neovascularization of the implants was analyzed by intravital fluorescence microscopy. Microcirculatory observations were performed in the surrounding skin muscle, at the border zone of the implant, and in the center of the implant. The functional vessel density (FVD; mm/mm2), as the length of perfused microvessels per observation area, was measured by computer-assisted analysis. The FVD served as the parameter of neovascularization. At the end of the protocol, histological observation of hematoxylin/eosin-standard-stained sections was performed by light microscopy. The FVD in the center of the implant on day 8 was only observed in gas-plasma coated (8.8 +/- 10.2 mm/mm2) and Ca-P-coated implants (0.8 +/- 2.0 mm/mm2). None of the other groups showed perfused microvessels in the center of the implant on day 8 (p < 0.05). The FVD values in the center of the gas-plasma-coated and the Ca-P-coated implants were 20.7 +/- 8.2 and 19.2 +/- 15.5 mm/mm2 as compared with 7.1 +/- 17.4 and 7.7 +/- 5.9 mm/mm2 for collagen-coated and untreated implants on day 16. The histological examination confirmed the profound microvascular ingrowth into the matrix pores of the gas-plasma-treated and the Ca-P-coated copolymer matrices in the center of the implants. The study showed that the ingrowth of microvessels into PEGT/PBT matrices can be accelerated by Ca-P coating and gas plasma treatment in the dorsal skinfold chamber in mice. PMID- 17283431 TI - Effect of cytochrome c peroxidase on the corneal epithelial healing process after excimer laser photo-ablation in transgenic mice. AB - AIM: To evaluate the role of commercially prepared cytochrome c peroxidase eye drops in corneal epithelial healing of transgenic B6(A)-Rpe65rd12/J mice after excimer laser photo-ablation. MATERIALS AND METHODS: In our prospective animal series, 72 eyes of 36 mice had uneventful bilateral excimer laser photo-ablation. In each mouse, one eye received standard topical postoperative therapy with tobramycin, diclofenac, and dexamethasone eye drops plus cytochrome c peroxidase eye drops (two drops three times a day for 1 week or until corneal re epithelialization was complete, corresponding to 15,000 IU/day). The fellow eye served as the control and received standard postoperative therapy plus placebo. The mice were monitored daily, commencing on the day after surgery, for 7 days to evaluate the corneal re-epithelialization rate using a video slit lamp camera with cobalt blue light. The mean diameter of the corneal wounds was measured. Videotaped images were recorded and analyzed by computer planimetry. RESULTS: All eyes treated with cytochrome c peroxidase eye drops healed completely before day 5 after surgery, with a mean re-epithelialization time of 92 +/- (SD) 10 h; the mean re-epithelialization time was 121 +/- 8 h in the eyes receiving placebo (p < 0.05). There were no statistically significant differences between the two groups in corneal haze presentation during the follow-up period (p = 0.70), perhaps because the observation period was too short (7 days). However, the corneal clarity, on slit lamp biomicroscopy, in the study group was higher than that in the control group. No side effects or toxic effects were observed. CONCLUSIONS: These data suggest that cytochrome c peroxidase significantly accelerates epithelial healing after phototherapeutic keratectomy. Further clinical studies should be performed to prove the results obtained in this study and the long-term efficacy of cytochrome c peroxidase to prevent corneal haze. PMID- 17283432 TI - Primary lumbar hernia repair: the open approach. AB - BACKGROUND: Lumbar hernias arise through posterolateral abdominal wall defects, named inferior triangle (Petit) and superior triangle (Grynfelt). Most of the lumbar hernias are secondary to trauma or previous surgery, while primary lumbar hernias are rare. There are two possible surgical approaches: the anterior approach with lumbar incision and the laparoscopic (transabdominal or totally extraperitoneal) approach. METHODS: We present a series of nine surgical procedures for primary lumbar hernia in 7 adult patients (2 affected by bilateral hernias). Seven were Grynfelt hernias, and two were Petit hernias. All surgical repairs were performed using synthetic mesh placed in the extraperitoneal space, below the muscular layers, using a tension-free technique. RESULTS: There was no surgical complication, except for 1 case with a subcutaneous haematoma. The mean hospital stay was 2.3 days. All patients returned to normal daily activities within 15 days after surgery. After a median follow-up period of 25 months, there was no case of recurrence or postsurgical sequelae, such as pain or muscular weakness. CONCLUSIONS: Primary lumbar hernias are rare congenital defects of the abdominal wall. Repair of these rare hernias can be successfully performed via the anterior approach with the use of synthetic mesh - this method of repair is easy, safe, and effective. PMID- 17283433 TI - The role of simvastatin on postoperative peritoneal adhesion formation in an animal model. AB - AIM: The aim of this study is to show the effect of simvastatin on intra abdominal adhesion formation. METHOD: Adhesion formation was achieved by scratching the cecum and anterior abdominal wall following median laparotomy. Three different groups of 10 rats each were formed. In group I, 0.57 mg/kg/day simvastatin was injected intraperitoneally right after the operation and for 5 days thereafter. In group II, an equal dose of simvastatin to that used in group I was given via gavage. A physiological saline solution was given to group III for the same period of time. On the 6th and 14th day, blood samples were taken and peritoneal lavage was performed to measure the tissue-type plasminogen activator (t-PA) activity. Adhesions were graded via re-laparotomies on the 14th day after the first operation. RESULTS: The adhesion scores were 1.40 +/- 0.22, 1.50 +/- 0.26, and 2.90 +/- 0.34 in groups I, II, and III, respectively (p = 0.007), and the score was higher in group III than in the other groups (p = 0.005, p = 0.011). CONCLUSION: Intraperitoneal simvastatin application decreases adhesion formation by increasing the t-PA level in abdominal surgery. PMID- 17283434 TI - [Aesthetic and functional corrections of the female genital area]. AB - In the last few years, we have performed an increasing number of genital reshaping procedures in females. Most frequently we carried out corrections of the labia, followed by operations to reduce the size of the clitoris and the pubic area. Psychological as well as functional complaints were the reasons for the decision to undergo a surgical correction. After a large number of operations we have gained great experience and developed specific operation techniques. The results are functionally reliable and aesthetically pleasing with a very low rate of complications and a high level of patient satisfaction. PMID- 17283435 TI - Genes, environment, health, and disease: facing up to complexity. PMID- 17283436 TI - Detection of gene x gene interactions in genome-wide association studies of human population data. AB - Empirical evidence supporting the commonality of gene x gene interactions, coupled with frequent failure to replicate results from previous association studies, has prompted statisticians to develop methods to handle this important subject. Nonparametric methods have generated intense interest because of their capacity to handle high-dimensional data. Genome-wide association analysis of large-scale SNP data is challenging mathematically and computationally. In this paper, we describe major issues and questions arising from this challenge, along with methodological implications. Data reduction and pattern recognition methods seem to be the new frontiers in efforts to detect gene x gene interactions comprehensively. Currently, there is no single method that is recognized as the 'best' for detecting, characterizing, and interpreting gene x gene interactions. Instead, a combination of approaches with the aim of balancing their specific strengths may be the optimal approach to investigate gene x gene interactions in human data. PMID- 17283437 TI - Strategy for detecting susceptibility genes with weak or no marginal effect. AB - Most human diseases result from complex interactions among multiple genes that yield weak or modest effects. Despite the growing awareness of the importance of gene-gene interactions, the paradigm of detectable effects of individual variants remains the cornerstone of genome association studies with tagSNPs. The interactive effect of two variants is only tested once the individual effect of one variant is detected. Both genes, however, may have at the same time a weak (or even no) marginal effect but an important effect through their interaction. In such a situation, current approaches may fail to detect variants having a crucial role in the causal chain. Here, we propose a new strategy: the 2-locus TDT. It allows the detection of the involvement of two genes without individual effect. Our strategy simultaneously uses information on biallelic candidate polymorphisms in two genes M and N. We first estimate the relative marginal penetrances of the genotype at each locus and of the joint (two-locus) genotype and then we test for the interactive effect of the two genes using a likelihood ratio test. We show that our approach has good power to detect the effect of two genes in situations for which a locus-by-locus strategy would have been unsuccessful. At a time where genome-wide association studies are fashionable, we think it is important to consider the strategy of studying good candidate pathways with our approach. PMID- 17283438 TI - The use of the restricted partition method with case-control data. AB - BACKGROUND/AIMS: Many diseases important to public health are not due solely to a single mutation or environmental insult. Instead, complex interactions among multiple genes and environmental exposures likely play crucial roles in the etiology of diverse phenotypes from schizophrenia to chemotherapy response. The Restricted Partition Method (RPM) was designed to detect qualitative genetic and environmental factors contributing to a quantitative trait, even if the contribution is predominantly presented as an interaction (displaying little or no signal in univariate analyses). Although the RPM was developed with the expectation that trait values would be drawn from normal distributions, the algorithm will function if the quantitative trait values are replaced with 0's or 1's indicating control or case status. The aim of this study is to evaluate the performance of the RPM on case-control data. METHODS: Case-control data simulated for this study and data provided to the Pharmcogenetics Research Network Analysis Workshop 2005 were used to assess power and type I error for the RPM in this setting. RESULTS: For the tested data, the RPM displayed good power and type I error very close to nominal rates. CONCLUSIONS: The RPM is an appropriate method for the analysis of case-control data. PMID- 17283439 TI - The impact of genotype misclassification errors on the power to detect a gene environment interaction using cox proportional hazards modeling. AB - This paper extends gene-environment (G x E) interaction study designs in which the gene (G) is known and the environmental variable (E) is specified to the analysis of 'time-to-event' data, using Cox proportional hazards (PH) modeling. The objectives are to assess whether a random sample of subjects can be used to detect a specific G x E interaction and to study the sensitivity of the power of PH modeling to genotype misclassification. We find that a random sample of 2,100 is sufficient to detect a moderate G x E interaction. The increase in sample size necessary (SSN) to maintain Type I and Type II error rates is calculated for each of the 6 genotyping errors for both dominant and recessive modes of inheritance (MOI). The increase in SSN required is relatively small when each genotyping error rate is less than 1% and the disease allele frequency is between 0.2 and 0.5. The genotyping errors that require the greatest increase in SSN are any misclassification of a subject without the at-risk genotype as having the at-risk genotype. Such errors require an indefinitely large increase in SSN as the disease allele frequency approaches 0, suggesting that it is especially important that subjects recorded as having the at-risk genotype be correctly genotyped. Additionally, for a dominant MOI, large increases in SSN can occur with large disease allele frequency. PMID- 17283440 TI - Exploiting gene-environment interaction to detect genetic associations. AB - Complex disease by definition results from the interplay of genetic and environmental factors. However, it is currently unclear how gene-environment interaction can best be used to locate complex disease susceptibility loci, particularly in the context of studies where between 1,000 and 1,000,000 markers are scanned for association with disease. We present a joint test of marginal association and gene-environment interaction for case-control data. We compare the power and sample size requirements of this joint test to other analyses: the marginal test of genetic association, the standard test for gene-environment interaction based on logistic regression, and the case-only test for interaction that exploits gene-environment independence. Although for many penetrance models the joint test of genetic marginal effect and interaction is not the most powerful, it is nearly optimal across all penetrance models we considered. In particular, it generally has better power than the marginal test when the genetic effect is restricted to exposed subjects and much better power than the tests of gene-environment interaction when the genetic effect is not restricted to a particular exposure level. This makes the joint test an attractive tool for large scale association scans where the true gene-environment interaction model is unknown. PMID- 17283441 TI - Symbolic modeling of epistasis. AB - The workhorse of modern genetic analysis is the parametric linear model. The advantages of the linear modeling framework are many and include a mathematical understanding of the model fitting process and ease of interpretation. However, an important limitation is that linear models make assumptions about the nature of the data being modeled. This assumption may not be realistic for complex biological systems such as disease susceptibility where nonlinearities in the genotype to phenotype mapping relationship that result from epistasis, plastic reaction norms, locus heterogeneity, and phenocopy, for example, are the norm rather than the exception. We have previously developed a flexible modeling approach called symbolic discriminant analysis (SDA) that makes no assumptions about the patterns in the data. Rather, SDA lets the data dictate the size, shape, and complexity of a symbolic discriminant function that could include any set of mathematical functions from a list of candidates supplied by the user. Here, we outline a new five step process for symbolic model discovery that uses genetic programming (GP) for coarse-grained stochastic searching, experimental design for parameter optimization, graphical modeling for generating expert knowledge, and estimation of distribution algorithms for fine-grained stochastic searching. Finally, we introduce function mapping as a new method for interpreting symbolic discriminant functions. We show that function mapping when combined with measures of interaction information facilitates statistical interpretation by providing a graphical approach to decomposing complex models to highlight synergistic, redundant, and independent effects of polymorphisms and their composite functions. We illustrate this five step SDA modeling process with a real case-control dataset. PMID- 17283442 TI - Assessing environmental modifiers of disease risk associated with rare mutations. AB - OBJECTIVE: As disease-predisposing mutations are increasingly identified, there is growing need to assess the effects of lifestyle and environmental factors on disease risks in mutation carriers. Such assessment is difficult when the mutations are rare and evaluating them in large population samples is costly. METHODS: This paper describes four study designs for evaluating the effects of environmental exposures in carriers of rare disease-predisposing mutations. RESULTS: The strengths and weaknesses of the designs are assessed, and strategies for analyzing the data obtained from such designs are considered. CONCLUSIONS: When exposure effects in noncarriers are well-established and exposure is independent of carrier status in the population of disease-free controls, the case-only design provides a feasible and efficient method for inferring effects in carriers. When exposure effects in noncarriers are not well established, the most feasible design options are those that compare exposures in carrier cases to either untyped controls or to carrier controls. These two designs have complementary strengths and weaknesses; thus inferences are stronger when measures of association estimated using the two designs are consistent. PMID- 17283443 TI - Accounting for epistasis in linkage analysis of general pedigrees. AB - Complex traits are generally believed to be influenced by multiple loci. Identification of loci involved in complex traits is more difficult for interacting than for additive loci. Here we describe an extension of the program lm_twoqtl in the package MORGAN to handle two quantitative trait loci (QTLs) with gene-gene interaction. We investigate whether parametric linkage analysis that accounts for such epistasis improves prospects for linkage detection and accuracy of localization of QTLs. Through use of simulated data we show that analysis that accounts for epistasis provides higher lod scores and better localization than does analysis without epistasis. In addition, we demonstrate that the difference between lod scores in the presence vs. absence of use of an interaction model in analysis is greater in extended than in nuclear pedigrees. PMID- 17283444 TI - Novel single nucleotide polymorphisms in the specific protein 1 binding site of the bovine PRNP promoter in Japanese Black cattle: impairment of its promoter activity. AB - Susceptibility to transmissible spongiform encephalopathy and different alleles of the prion protein gene (PRNP) of humans and sheep are associated. A tentative association between PRNP promoter polymorphisms and bovine spongiform encephalopathy (BSE) susceptibility has been reported in German cattle, whereas none of the known polymorphisms within the bovine PRNP-coding sequence affect BSE susceptibility. In the present study, novel single nucleotide polymorphisms located in the 5'-flanking region of bovine PRNP affecting its expression were demonstrated in Japanese Black cattle. We sequenced exon 1, and the approximately 200-bp 5'-flanking region of the PRNP translation initiation site containing the proximal promoter of PRNP was harvested. We identified 7 single nucleotide polymorphisms: -184A-->G, -141T-->C, -85T-->G, -47C-->A, -6C-->T, +17C-->T and +43C-->T. Six segregated haplotypes in the population were cloned into luciferase expressing plasmids, transfected into N2a cells, and their reporter activities were measured 48 h after transfection. Six haplotypes showed a decreased expression level including -6C-->T in specific protein 1 binding site (p < 0.05) or -141T-->C (p < 0.01) at 48 h compared with the wild-type haplotype. These results advocate that certain polymorphisms such as specific protein 1 binding site polymorphisms in the bovine PRNP promoter region in Japanese Black cattle could influence promoter activity, suggesting that breeding cattle with such substitutions may be a useful approach in reducing BSE risk. PMID- 17283445 TI - Reliable generation of stable high titer producer cell lines for gene therapy. AB - OBJECTIVE: Retroviral vectors represent one of the most robust technologies for in vivo expression of heterologous gene sequences and are still the most commonly used vectors in clinical gene therapy trials. The production of high titer retroviral preparations, however, can be a problematic procedure for certain constructs. METHODS: GALV- or RD114-pseudotyped retroviral particles carrying selectable fluorescence markers or drug resistance genes, such as the green fluorescent protein (GFP) or the O(6)-methylguanine-DNA-methyltransferase (MGMT) mutants, were used to stably transduce Phoenix-(FNX-)eco cells. Thereafter, a polyclonal population of producer cells was generated by enriching cells with high marker gene expression. In addition, single producer clones were selected by limiting dilution. RESULTS: Retroviral titers were increased 1-2 logs by enriching for a polyclonal population of producer cells, and selection of single producer clones allowed another 1- to 2-log increase in titers. Using this method, reproducibly high titer viral preparations allowing efficient transduction of hematopoietic stem cells were generated. CONCLUSION: A reliable and time-effective method to generate stable high titer producer cells based on the FNX-cell line for problematic retroviral vector constructs is described. PMID- 17283447 TI - Circulating hepatitis B virus RNA in newborns from carrier mothers. AB - OBJECTIVE: Despite intermittent flares, progression of chronic infection with hepatitis B virus has generally been related to a decrease in replication levels. In our laboratory, this decrease has been found to be associated with a decline in circulating full-length transcripts (fRNA) and to a shift to truncated transcripts (trRNA). Monitoring fRNA and trRNA as markers allows a more detailed analysis of high or low or non-replicative HBV infection stages. METHODS: Here, we determined circulating HBV RNA in newborns from a total of 69 HBsAg-positive carrier mothers with and without immunotherapy administered during the last 3 months of pregnancy. RESULTS: In line with previous observations, serum HBV DNA in newborns was only found when their mothers had not been treated (7/23). HBV RNA measured as trRNA was detected both in the presence and in apparent absence of serum HBV DNA. fRNA (coexisting with HBV DNA and HBeAg) was detected only in newborns from untreated mothers (8/23) and was always combined with trRNA. In contrast, trRNA was found in newborns from both untreated (20/23) and treated mothers (26/46). CONCLUSIONS: Our data strongly suggest a direct intrauterine transmission of a low-replicative (unapparent) HBV infection stage. However, a feto-maternal transfer of trRNA (transfer of a marker) rather than transmission of the infectious virus cannot be excluded. PMID- 17283446 TI - In vitro study of antiviral activity of mycophenolic acid on Brazilian orthobunyaviruses. AB - OBJECTIVE: Oropouche, Caraparu, Guama, Guaroa and Tacaiuma are ssRNA viruses that belong to the genus Orthobunyavirus and have been associated with human febrile illnesses and/or encephalitis. In this study, we evaluated the antiviral action of mycophenolic acid (MPA) on theseorthobunyaviruses to achieve a therapeutic agent to treat the diseases caused by these viruses. METHODS: The in vitro antiviral evaluation to MPA was done by using plaque assay at different periods of treatment. RESULTS: Results showed that MPA at a concentration of 10 microg/ml has significant antiviral activity on Tacaiuma virus when treatment was initiated either 24 h before or 2 h after viral infection. Moreover, MPA has an inhibitory effect on Guama virus replication, but only when treatment was initiated before cell infection. Addition of guanosine in the culture reverted the inhibitory effect of MPA on Tacaiuma and Guama viruses, suggesting that the antiviral activity of this substance was via depletion of the intracellular guanosine pool. CONCLUSION: Our results suggest that MPA would not be a good therapeutic agent to treat the diseases caused by Oropouche, Caraparu, Guama, Guaroa, and Tacaiuma viruses. PMID- 17283448 TI - In vitro interaction of poliovirus with cytoplasmic dynein. AB - OBJECTIVE: Poliovirus (PV) enters the host by the oral route and can infect the central nervous system (CNS) by two mechanisms: crossing the blood-brain barrier and traveling along the nerves from the muscle to the spinal cord. In the latter mechanism, the PV receptor, CD155, and the motor protein, dynein, have been implicated in the transport of PV to the CNS. In this work we analyzed the possible interaction of PV with dynein. METHODS: PV was bound to a Sepharose 4B beads and they were used to analyze the interaction of PV with cytoplasmic proteins from neuroblastoma cells by affinity chromatography and Western blot. RESULTS: The interaction with cytoplasmic dynein was observed only when the Sepharose beads bound to PV were used and not in the control ones, where proteins from uninfected cells were coupled. CONCLUSION: These preliminary results open the possibility that PV uses the dynein directly in its retrograde axonal transport. PMID- 17283449 TI - Management of multiple myeloma with bortezomib: experts review the data and debate the issues. AB - Cure for multiple myeloma is rare; the success of treatment is measured by response, and length of remissions and survival. Initial treatment for patients young and fit enough is high-dose chemotherapy with autologous stem cell transplantation. Various chemotherapy regimens are employed as initial therapy in patients who cannot withstand the autologous stem cell transplantation regimen, and for treatment of refractory or relapsed disease. Commonly used agents either alone or in combination have included dexamethasone, vincristine, doxorubicin, melphalan, cyclophosphamide, etoposide, cisplatin and, more recently, thalidomide. Within the past few years, the first-in-class proteasome inhibitor bortezomib has been introduced for the treatment of relapsed multiple myeloma with data demonstrating efficacy and safety. Throughout Europe, a faculty of experts conducted a series of debates with over 450 clinicians to discuss the efficacy of bortezomib vis-a-vis other available therapies. Of primary concern was the place of bortezomib in maximizing efficacy throughout the course of the disease and treatment by increasing response rates and improving duration of response, while maintaining an acceptable level of toxicity. The experts concluded that bortezomib, with its unique mechanism of action and demonstrated clinical efficacy and safety, should be considered as standard, early treatment in patients with relapsed multiple myeloma, especially after first relapse. PMID- 17283450 TI - The management of adenocarcinoma of the rectum. PMID- 17283451 TI - Histocompatibility antigens in Omanis: Comparison with other Gulf populations and implications for disease association. AB - BACKGROUND: This is the first comprehensive report of HLA antigens in Omanis, and the first application of HLA sequence-specific primer (SSP) DNA typing in a Gulf population. The objective was to compare the findings with other Gulf populations and assess their implications for disease association. PATIENTS AND METHODS: HLA typing was carried out on 321 healthy Omanis. One hundred and twenty-six of these were typed for Class II antigens by low-resolution SSP DNA typing. The results were compared with other HLA antigen frequencies recorded from Kuwait and Saudi Arabia. RESULTS: The Omani population was characterized by a very high incidence of HLA-DR2 (66%), with associated HLA-DQ1 (76%) and a reduced incidence of DR4, DR7 and DR53. The incidence of DR2 is the highest recorded worldwide. HLA-A11, A32, B17, B35 and B40 were significantly higher than in Kuwait and Saudi Arabia, and A9, B21(B50) significantly lower (Pc<0.05). HLA-B27 is very low in the Omani population (0.3%). The high incidence of HLA-DR2 in Oman and disparities in the frequency of other antigens would indicate that there has not been any significant migration from northern Arabia. Class II DNA typing revealed that DR16 was the predominant split of DR2 (63%), with DR15 being 18% and both DR15 and 16 being found in 6%, giving a total of 87% for A centAADR2A centAA associated antigens (serology of the same individuals gave a DR2 incidence of 74%). The major disparity between serology and DNA typing was in the definition of DR4 (serology 8%, DNA 14%) and DR51 (53% vs. 70%). CONCLUSION: The frequency of many HLA antigens in Omanis differs significantly from frequencies found in the populations of Kuwait and Saudi Arabia, possibly reflecting different migration patterns. The high incidence of HLA-DR2 in Oman may have important implications for disease association. PMID- 17283452 TI - Clustering of trisomy 18 in Kuwait: Genetic predisposition or environmental? AB - BACKGROUND: This study describes 59 newborns with regular trisomy 18 (EdwardsA centAA syndrome, T18) who were ascertained clinically and cytogenetically at the Kuwait Medical Genetic Centre from 1994 to 1997, out of 118 T18 cases identified from 1980 to 1997. MATERIALS AND METHODS: T18 cases were ascertained clinically and cytogenetically shortly after birth. In addition to assessing the T18 birth prevalence rate and confidence limits during the years 1994-1997, we investigated the possible etiological factors by a case-control study with normal healthy newborns. Studied factors included gender, parental age, birth order, abortion, clinical variables (presentation, amniotic fluid and mode of delivery), and survival. RESULTS: The average T18 birth prevalence rate during the period was 8.95 per 10,000 live births (95% confidence limits 6.66-11.23). The T18 cases were mostly females, with a male:female ratio of 1:2.1, and the majority (53%) died before the second week of life. Maternal age above 30 years was found to be a significant factor for T18. CONCLUSION: This high T18 birth prevalence rate suggests clustering of T18 in the highly inbred population of Kuwait. Such clustering may indicate a possible environmental, and to a lesser extent, genetic predisposition to aneuploidy nondisjunction. PMID- 17283453 TI - Polymorphism in apoprotein-CIII gene and coronary heart disease. AB - BACKGROUND: The aim of this study was to look into the association, if any, of apoprotein-CIII variant allele with hypertriglyceridemia, hypercholesterolemia and coronary heart disease (CHD). PATIENTS AND METHODS: The prevalence of a C to G substitution in the 3' untranslated region of apoprotein-CIII was studied in a sample of 92 angiographed Saudi subjects, consisting of 65 males and 27 females. The subjects were genotyped by amplification followed by digestion of the gene fragment containing the polymorphic site with Sac I restriction enzyme. RESULTS: The variant allele of apoprotein-CIII was found to be associated neither with hypertriglyceridemia nor with hypercholesterolemia. However, a significant association of this allele (P<0.01) was found with coronary heart disease, independent of other risk factors such as smoking, diabetes and hypertension. An estimation of odds ratio using logistic regression with various risk factors in the model showed that the individuals with this rare allele were 3.4 times more at risk of developing coronary heart disease. This estimate of risk held even after analyzing a subset of individuals above 45 years of age. CONCLUSION: While the association between apoprotein-CIII variant allele and dyslipidemia could not be established in this study, the relationship between this marker and CHD was highlighted in the studied subjects. PMID- 17283454 TI - Prevalence and social correlates to consanguinity in Kuwait. AB - BACKGROUND: Kuwait has one of the highest consanguinity rates in the world. Our objectives in this study were to assess the frequency and trend in consanguineous marriages, and to identify factors associated with inbreeding. PATIENTS AND METHODS: A representative sample of 482 households from the most developed (the Capital), and the least developed (Jahra), of the five governorates in Kuwait was selected. The study involved only Kuwaiti nationals. A structured questionnaire was administered by previously trained team members through a household face-to face interview. RESULTS: Data were obtained for 959 current or previous marriages. Frequency of total (first and second cousin) consanguinity was much higher in Jahra governorate (42.1%) than the Capital (22.6%). Over the last decade, the inbreeding has decreased in the Capital but not in Jahra. Bivariate analysis indicated that several socioeconomic and demographic variables were significantly associated with consanguinity. The control of confounding factors by logistic regression showed, however, that Bedouin origin and year of marriage were the only variables significantly related to consanguinity. CONCLUSION: There is a widening gap between Bedouins and non-Bedouins in the practice of consanguinity in Kuwait. PMID- 17283455 TI - The effects of aging on muscle strength and functional ability of healthy Saudi Arabian males. AB - BACKGROUND: Loss of muscle strength as a result of normal aging is reported to impair functional ability in various communities. The purpose of this study was to determine the age at which loss of muscle strength and functional ability begins, and to establish a preliminary baseline for the pattern of changes in muscle strength and functional ability of aging in adult healthy Saudi Arabian males. SUBJECTS AND METHODS: A sample of 160 healthy Saudi Arabian males aged 20 89 years participated in this study. The subjects were divided into seven age groups, each representing a decade. Maximum isometric A centAAmakeA centAA strength of bilateral quadriceps muscles were measured using a hand-held dynamometer. Functional ability tests that included stair walking, timed-up-and go and balance tests were also performed and timed using a digital stopwatch. RESULTS: Muscle strength and functional ability remained unchanged in the 20- and 30-year-old age groups. Around the age of 40, muscle strength and functional ability began to gradually decline. Muscle strength of males in their twenties was 380+/-62N and 330+/-60N in the right (RT) and left (LT) quadriceps, respectively. A decline with aging is represented by 190+/-40N and 110+/-30N in the RT and LT quadriceps muscles, respectively, by the eighth decade of life. Stair-walking, timed up-and-go and balance tests in the second decade were 4+/-1 sec, 8+/-2 sec and 130+/-20 sec, respectively, against 15+/-4 sec, 26+/-7 sec and 15+/-5 sec in the eighth decade. One-way ANOVA test showed that muscle strength and functional ability differed (P<0.01) among decades, except between the second and third decades (P<0.31). Age, muscle strength and functional ability displayed a significant relationship (P<0.001). CONCLUSION: Loss of muscle strength and functional ability seem to begin in the fourth decade of life. The changes in muscle strength and functional ability have a significant relationship to aging. Clinically, these results may provide clinicians with a guide to the strength level of normal quadriceps and the functional ability of adult healthy Saudi Arabian males in relation to the normal aging process. PMID- 17283456 TI - Survival after liver transplantation: Experience with 89 cases. AB - BACKGROUND: Liver transplantation has become an accepted clinical modality in the treatment of end-stage liver disease since the early eighties. In this paper, the result of liver transplantation at the largest liver transplant center in Saudi Arabia is presented with a special emphasis on the difficulties hindering the expansion of such programs. PATIENTS AND METHODS: A series of 89 liver transplant procedures was performed between January 1994 and June 1998. This is the largest series of liver transplant cases reported to date in Saudi Arabia. Patient data were retrospectively analyzed with a special emphasis on mortality and morbidity. Kaplan-Meier technique was used to compute patient survival. RESULT: The final outcome of the transplants was found to be comparable to that of well-established programs in Western Europe and North America. The actuarial survival rate at three months and one year was 98% and 89%, respectively. The long-term survival rate (>3 years) was 67%. Technical complications were well below average. The dominating cause of early death was sepsis. Late death was generally due to disease recurrence and chronic rejection. CONCLUSION: Liver transplantation has been successful in Saudi Arabia. However, the main obstacle to program expansion and, therefore, the salvage of patients with end-stage organ failure, is lack of organs. This situation can be resolved only if all parties involved in organ transplantation in Saudi Arabia take serious steps towards the alleviation of the problem of organ shortage. Improvement in the donor situation in the Kingdom should result in timely retransplantation of patients with primary graft non function and hepatic artery thrombosis, and will certainly enhance their chances of survival. PMID- 17283457 TI - Seroepidemiology survey of brucellosis antibodies in Saudi Arabia. AB - BACKGROUND: Brucellosis is considered the most important zoonosis in Saudi Arabia, with a high prevalence among man and livestock. PATIENTS AND METHODS: A natural survey of 23,613 subjects was conducted in 1997, in order to assess the seroprevalence of brucellosis in Saudi Arabia. Investigations included interviews, clinical examination and blood sampling for antibody determination, using the standard tube agglutination test (STAT). RESULTS: The result of the study revealed that the seroprevalence of brucellosis was 15%. The seroprevalence increased by age, and was higher in rural areas, and among people in high-risk occupations. CONCLUSION: Direct contact with domestic animals and consumption of raw products of animal origin were identified as the main risk factors. PMID- 17283458 TI - Dermatitis artefacta: A review of 14 cases. AB - BACKGROUND: Dermatitis artefacta (DA) is a self-inflicted dermatologic injury sometimes produced for secondary gains. Laboratory investigations, including histologic examination of lesional tissue biopsy, are usually negative and do not give a clue to the correct diagnosis. PATIENTS AND METHODS: Over a five-year period, 14 patients were diagnosed with DA at King Fahad Hospital (KFH) in Al Baha during routine outpatient and inpatient dermatologic consultations. The diagnoses were based on vagueness of history given by the patients, and the presence of bizarre skin lesions distributed over sites accessible to the patientsA centAA hands. Investigations excluded the possibility of other diseases. In some cases, consultant psychiatric assessment was sought in order to identify possible underlying psychopathologic factors. Seven patients were hospitalized while the rest were managed as outpatients. RESULTS: The 14 patients comprised 12 females and two males aged 12 to 71 (mean 25.9) years. All except one were Saudis. DA in the males was probably caused for secondary gains. The females, four of whom were married and eight single, were aged 12-36 (mean 21.8) years. Nine of the females (64%) had identifiable severe emotional or psychiatric problems. The remaining two were unmarried and had no identifiable underlying factors. CONCLUSION: This study reveals that the presentation of DA in Saudi Arabia is essentially similar to what has been reported from other parts of the world. It brings into focus a medical problem which needs to be recognized, as greater awareness may bring about earlier correct diagnosis and treatment. PMID- 17283459 TI - Tuberculin test conversion among employees of a tertiary care hospital in Riyadh, Saudi Arabia. AB - BACKGROUND: The objective of this study was to determine the tuberculin skin test conversion rate, as well as the course and outcome of the converters, among employees of a tertiary care hospital. The study is a retrospective, cohort descriptive study undertaken at the King Faisal Specialist Hospital and Research Centre, in Riyadh, Saudi Arabia. PATIENTS AND METHODS: The study was undertaken over a four-year period from 1993 to 1996, and the subjects were employees who had annual screening PPD skin tests. The outcome measures skin test conversion, prophylactic treatment with isoniazid (INH), side effects, and development of clinical tuberculosis. RESULTS: A total of 6883 tuberculin skin tests were performed during the study period. The mean annual conversion rate was 1.55%. About 78% of the converters received INH prophylaxis, but only 75% of those who started chemoprophylaxis completed the course. The side effects of INH treatment were found in 23% of those on treatment, and one of the converters developed clinically active tuberculosis during the study period. CONCLUSION: At the King Faisal Specialist Hospital and Research Centre, the mean annual tuberculin skin test conversion rate among employees is similar to that found in other studies, but compliance to oral isoniazide prophylaxis is low. There is a need to develop strategies to improve compliance. PMID- 17283460 TI - Atrial fibrillation: A review of the management in the emergency department. PMID- 17283461 TI - Acute chylous peritonitis simulating acute appendicitis: A case report and review of the literature. PMID- 17283462 TI - Hemoperitoneum secondary to exogastric leiomyoblastoma of the stomach. PMID- 17283463 TI - Pyogenic spinal epidural abscess. PMID- 17283465 TI - Choloroquine-resistant Plasmodium falciparum malaria in an extremely premature infant. PMID- 17283464 TI - Recurrent stage 1 borderline serous ovarian tumor. PMID- 17283467 TI - Symptomtic cholelithiasis in children: A hospital-based review. PMID- 17283466 TI - Rhabdomyolysis and acute renal failure in a case of child abuse. PMID- 17283468 TI - Smoking among physicians in Syria: Do as I say, not as I do! PMID- 17283469 TI - Wilms' Tumor: The Tawam Hospital experience. PMID- 17283471 TI - Serum creatine kinase: A marker for muscle damage in sickle cell painful crisis. PMID- 17283470 TI - Diagnostic reliability of combined approach of physical examination, mammography and fine-needle aspiration biopsy in patients with breast cancer. PMID- 17283472 TI - Routine feeding practices in a university hospital in Riyadh: Are they baby friendly? PMID- 17283473 TI - Single center experience of en bloc kidney transplantation and review of the literature. PMID- 17283474 TI - Choanal atresia repair: 14 years' experience. PMID- 17283476 TI - Can breast cancer be prevented? PMID- 17283475 TI - Anastomosis workshops: The Saudi experience. PMID- 17283477 TI - Pediculus humanus capitis infestation in a Shiraz rural area, Iran. PMID- 17283478 TI - Congenital anomalies on endoscopic retrograde cholangiopancreatography (ERCP). PMID- 17283479 TI - Paralytic ileus: A possible complication of cefuroxime. PMID- 17283480 TI - Reply: Sickle cell disease in the Kingdom of Saudi Arabia: East and West. PMID- 17283481 TI - Sickle cell disease in the Kingdom of Saudi Arabia: East and West. PMID- 17283483 TI - By the way, doctor. My doctor told me my heart is growing. He says there is no cure. Do you know of anything to reverse or slow down the growing heart? I am an 86-year-old World War II veteran. PMID- 17283484 TI - Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat. AB - Induction of hematopoietic chimerism and subsequent donor-specific immune tolerance via bone marrow transplantation is an ideal approach for islet transplantation to treat type-1 diabetes. We examined the potential of mesenchymal stem cells (MSCs) in the induction of chimerism and islet allograft tolerance without the incidence of graft-versus-host disease (GVHD). Streptozotocin-diabetic rats received a conditioning regimen consisting of antilymphocyte serum and 5 Gy total body irradiation, followed by an intraportal co-infusion of allogeneic MSCs, bone marrow cells (BMCs) and islets. Although all the recipients rejected the islets initially, half of them developed stable mixed chimerism and donor-specific immune tolerance, shown by the engraftment of donor skin and second-set islet transplants and acute rejection of a third-party skin. The engraftment of the primary islet allografts with stable chimerism was achieved by the addition of a 2-week peritransplant administration of 15 deoxyspergualin (DSG). Without MSCs, none of the recipients treated with DSG developed chimerism or reversal of diabetes. GVHD was not observed in any of the recipients infused with MSCs (0/15), whereas it occurred in 4/11 recipients without MSCs. These results indicate a potential use of MSCs for induction of hematopoietic chimerism and subsequent immune tolerance in clinical islet transplantation. PMID- 17283485 TI - Infiltrates in protocol biopsies from renal allografts. AB - In renal transplantation, clinical decisions are based primarily on the Banff classification of biopsies. However, the incorporation of 'minor or nonspecific' cellular infiltrates into the Banff classification and their interpretation is uncertain. We analyzed 833 protocol and 306 indicated biopsies to test whether such infiltrates are harmless or whether they have a bearing on outcomes. We characterized morphology, localization and cellular composition of infiltrates, and correlated these findings to the Banff classification and allograft outcome. We found that protocol biopsies had the same prevalence of infiltrates as indication biopsies (87% vs. 87%). Diffuse cortical infiltrates, the hallmark of cellular rejection were more common in indication biopsies and related to tubulitis and a rise in serum creatinine. However, in biopsies with cellular rejection according to Banff criteria, we observed an increase in all infiltrate types (specific and nonspecific) and all cell types (T cells, B cells, histiocytes). The only predictor of allograft function outcome was persistent inflammation in sequential biopsies, irrespective of type, localization and composition of the cellular infiltrates. As detected by sequential biopsies, persistence of any inflammation including those infiltrates currently not considered by the Banff classification should be regarded as a morphological correlate of ongoing allograft damage. PMID- 17283486 TI - Mycophenolate mofetil is associated with altered expression of chronic renal transplant histology. AB - Mycophenolate mofetil (MMF) reduces acute rejection in controlled trials of kidney transplantation and is associated with better registry graft survival. Recent experimental studies have demonstrated additional antifibrotic properties of MMF, however, human histological data are lacking. We evaluated sequential prospective protocol kidney biopsies from two historical cohorts treated with cyclosporine (CSA)-based triple therapy including prednisolone and either MMF (n = 25) or azathioprine (AZA, n = 25). Biopsies (n = 360) were taken from euglycemic kidney-pancreas transplant recipients. Histology was independently assessed by the Banff schema and electron microscopic morphometry. MMF reduced acute rejection and OKT3 use (p < 0.05) compared with AZA. MMF therapy was associated with limited chronic interstitial fibrosis, striped fibrosis and periglomerular fibrosis (p < 0.05-0.001), mesangial matrix accumulation (p < 0.01), chronic glomerulopathy scores (p < 0.05) and glomerulosclerosis (p < 0.05). MMF was associated with delayed expression of CSA nephrotoxicity, reduced arteriolar hyalinosis, striped fibrosis and tubular microcalcification (p < 0.05 0.001). The beneficial effects of MMF remained in recipients without acute rejection. Retrospective analysis shows that MMF therapy was associated with substantially reduced fibrosis in the glomerular, microvascular and interstitial compartments, and a delayed expression of CSA nephrotoxicity. These outcomes may be due to a limitation of immune-mediated injury and suggest a direct effect of reduced fibrogenesis. PMID- 17283488 TI - The cellular lesion of humoral rejection: predominant recruitment of monocytes to peritubular and glomerular capillaries. AB - Accumulation of inflammatory cells within capillaries is a common morphologic feature of humoral renal allograft rejection and is most easily appreciated if it occurs in glomeruli. The aim of our study was to determine the amount and composition of immune cells within glomeruli and peritubular capillaries (PTC) in cellular and humoral allograft rejection. Immunofluorescent double-labeling for CD31 and CD3 or CD68 was used for phenotyping and enumerating immune cells within glomeruli and PTC. The major findings are: (1) accumulation of immune cells in PTC is far more common than it would be anticipated based on the assessment by conventional histology; (2) it is not the absolute number of immune cells accumulating within capillaries, but rather the composition of the intracapillary cell population that distinguishes humoral rejection from cellular rejection and (3) in C4d positive biopsies a predominantly monocytic cell population accumulates not only within glomeruli but also within PTC. The median value of monocyte/T-cell ratio within PTC was 2.3 in C4d positive biopsies but only 1 (p = 0.0008) in C4d negative biopsies. Given their prominent presence within capillaries and their extensive biological versatility monocytes might contribute to the capillary damage observed in acute and chronic allograft rejection. PMID- 17283487 TI - Lymphatic neoangiogenesis in human renal allografts: results from sequential protocol biopsies. AB - Neoangiogenesis of lymphatic vessels may be important for the cellular immune response in renal transplants. To determine the prevalence and chronology of lymph vessel proliferation and its relation to cellular infiltrates and allograft function, we analyzed sequential protocol biopsies (n = 162), taken at 6, 12 and 26 weeks after transplantation. Biopsies were stained with an antibody against podoplanin and lymphatic vessel density was quantified per square millimeter. The prevalence of lymph vessel-positive biopsies and the lymph vessel density were similar at 6, 12 and 26 weeks after transplantation. Biopsies with acute cellular rejection showed no significantly different lymph vessel density compared to those below the threshold for acute rejection or chronic allograft nephropathy. While lymphatic neoangiogenesis was equally prevalent in biopsies with and without infiltrates, the lymph vessel density was significantly higher in areas with cellular infiltrates than in areas without. Graft function at 1 year after transplantation was better in cases with lymph vessels in their infiltrates compared to cases with lymph vessel-free infiltrates. In conclusion, lymphangiogenesis not only shows a clear association with cellular infiltrates but might also have an impact on the pathogenicity of these cellular infiltrates. PMID- 17283489 TI - Efficacy of a pre-S containing vaccine in patients receiving lamivudine prophylaxis after liver transplantation for chronic hepatitis B. AB - Lamivudine monoprophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants and second generation recombinant HBV vaccine is not effective. We studied the efficacy of two courses each of three double-doses (20 microg) of third generation recombinant pre-S containing vaccine (Sci-B-Vac) in 20 patients on lamivudine prophylaxis at a median of 637 days (range, 390-2666 days) after transplantation. At enrollment, all patients were seronegative for HBsAg, anti HBs and HBVDNA (by qPCR). Lamivudine (100 mg/day) was continued throughout the study. Five patients (25%) responded to the first course and five additional patients responded after the second course (overall response rate 50%). The response rate was 88% in patients younger than 50 years old and 25% in older patients (p = 0.02). The median peak anti-HBs titer was 153 mIU/mL with six responders having a titer >100 mIU/mL and seven sustained >6 months. Among seven previous nonresponders to second generation recombinant vaccine, three (44%) responded. At the end of the study, all patients remained seronegative for HBsAg. In conclusion, Sci-B-Vac is effective in about 50% of patients receiving lamividine prophylaxis and may prevent recurrence due to escape mutants. PMID- 17283490 TI - The outcome of heart transplant recipients following the development of end-stage renal disease: analysis of the Canadian Organ Replacement Register (CORR). AB - End-stage renal disease is a significant complication of heart transplantation (HTx), but our understanding of dialysis outcomes in HTx recipients remains limited. We performed a retrospective analysis looking at dialysis mortality in HTx recipients as compared to a matched dialysis cohort. We also examined outcomes with respect to kidney transplantation (KTx) in these cohorts. 2709 incident HTx recipients were captured from the Canadian Organ Replacement Register between 1981 and 2002. The incidence of dialysis after HTx was 3.9% (n = 105) and carried a greater crude mortality compared to HTx recipients not requiring dialysis (56.2% vs. 35.9%, p < 0.001). Compared to the matched dialysis cohort, survival of HTx patients on dialysis was also significantly worse (19% vs. 40%, p = 0.003). In those receiving a KTx, survival did not differ between the two cohorts; however, in those that did not receive a KTx the survival was significantly lower in the dialysis post-HTx group compared to the matched dialysis cohort (15.7% vs. 35.2%, p < 0.025). Our analysis suggests mortality on dialysis following HTx is greater than would be expected from a similar dialysis population, and KTx may abrogate some of this increased risk. Attention should be placed on preventing chronic kidney disease progression following HTx. PMID- 17283491 TI - Recovery of functional memory T cells in lung transplant recipients following induction therapy with alemtuzumab. AB - Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow and T Cell Memory, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4-5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R-) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R- patients predepletion may require a prolonged period of prophylaxis. PMID- 17283493 TI - DNA Repair 2006: ninth biennial meeting of the German Society for Research on DNA repair. AB - A comprehensive meeting on current aspects of DNA repair organized by, Jochen Dahm-Daphi, Ekkehard Dikomey, Alexander B_rkle, Marlis Frankenberg-Schwager, Frank Grosse, Andrea Hartwig, George Iliakis, Bernd Kaina, J_rgen Thomale, and Lisa Wiesm_ller was held in Hamburg, Germany from September 12 to 15, 2006. This article summarizes information of invited lectures and proferred papers of six plenary sessions. PMID- 17283492 TI - Acute sensory neuropathy associated with rabbit antithymocyte globulin. AB - Rabbit antithymocyte globulin (RATG) is indicated for the treatment of acute renal transplant rejection and has also been shown to be effective as an induction immunosuppressive agent after renal transplantation. We report a patient that developed a painful sensory neuropathy within an hour of receiving RATG. The neuropathic symptoms resolved within a month, and a careful review of his medications, exposures and comorbid conditions revealed no other causes of neuropathy. Since the administration of RATG and onset of symptoms were so closely related temporally and the symptoms resolved after the cessation of RATG, we believe it is likely this medication led to the development of neuropathy. PMID- 17283494 TI - Report of the Working Group on Integrated Translational Research in DNA Repair. AB - On September 28-29, 2006, the National Institute of Environmental Health Sciences led a team from the National Institutes of Health in hosting a Working Group on Integrated Translational Research in DNA Repair, in Berkeley, CA. In recognition of the far-reaching goals for this area of investigation, the Working Group was charged with conceiving a vision to facilitate projects that would apply the lessons of DNA Repair research to clinical application and public health. The participants included basic and physician scientists working in the various areas of DNA Repair and genome stability, as well as agency representatives of the National Cancer Institute and the National Institute of General Medical Sciences. In constructing this vision of practical research recommendations, the Working Group was asked to identify roadblocks to progress, suggest enabling technologies, and to consider areas that are ripe for translation. This report summarizes the rationale for this initiative and the recommendations that emerged. PMID- 17283495 TI - [Clinical and audiological findings in children with auditory neuropathy]. AB - BACKGROUND: Auditory neuropathy is a disorder characterised by preservation of outer hair cells function with normal otoacoustic emissions (OAEs), but with absent auditory brainstem responses (ABR). Perisynaptic synchronisation disorder is one of the possible pathogenesis underlying auditory neuropathy. In this paper we describe the clinical presentation and audiological findings in pediatric auditory neuropathy and its management. PATIENTS AND METHODS: 9 children with auditory neuropathy could be included in the study. An audiological evaluation was performed in all children including behavioural audiometry, measurement of the OAEs as well as electrocochleography (ECoG) and ABR recordings. Children who failed to get any benefit from conventional amplification received a cochlear implant. Prior to implantation the responses to electrical stimuli were examined with the promontory test and with the electrically evoked ABR. RESULTS: One child showed auditory neuropathy only on one side with normal hearing thresholds on the contralateral ear. Another child had normal hearing thresholds after the follow up period. Four children received a hearing aid. But variable hearing reactions were observed. Thus in three cases a CI is planned. In three children cochlea implantation was done. Following implantation a remarkable improvement in hearing/speech capabilities with the CI compared to conventional hearing aids were observed in all three cases. Beside, these three children developed open set speech discrimination and are using now oral language for communication. CONCLUSIONS: Auditory neuropathy is a disorder which presents with different clinical and audiological findings. Thus the management of this disorder must be an individual one. In light of our findings we support the use of cochlear implants as an option for children with auditory neuropathy in cases where conventional amplification does not work sufficiently. PMID- 17283497 TI - US FDA seeks more pharmaceutical industry cash. PMID- 17283496 TI - [Are there auditory processing and perception disorders in children with dyslexia?]. AB - BACKGROUND: In this paper the dichotic tests and the CERA (Cortical Evoked Response Audiometry) of children with dyslexia had been examined, in order to find out if there are auditory processing and perception disorders. PATIENTS AND METHODS: 33 children with dyslexia had been compared with 28 children without problems of writing and reading. The mean age of the children was 9 years. All of the children had been examined by the following audiometric measurements: tympanometry, pure-tone-audiometry, speech-audiometry, dichotic Tests by Uttenweiler and Feldmann and the Cortical Evoked Response Audiometry (CERA) rated according to Esser. RESULTS: The intelligence quotients were in the group of dyslexic children significantly lower. The Uttenweiler and Feldmann tests were in dyslexic children significantly lower in the control group as well. The late cortical responses ware normal or near normal in both groups. CONCLUSION: Dichotic speech tests indicate central auditory processing and perception deficits in dyslexia. These tests are confounded, however, by attention and memory deficits. The CERA rated according to Esser does not point out to these auditory disorders in dyslexia. PMID- 17283498 TI - HIV/AIDS conference highlights Lesotho's progress. PMID- 17283499 TI - Serbia rebuilds and reforms its health-care system. PMID- 17283500 TI - [5th International Symposium of Coloproctology in Yugoslavia. October 2006 in Sava Center, Belgrade]. PMID- 17283501 TI - Don't stop me now. PMID- 17283502 TI - Rebuttal to Dr. Rudo's December letter. PMID- 17283503 TI - Diabetes and the stars. Glamorous lives, real-life challenges. PMID- 17283504 TI - Taking your diabetes on a cruise. PMID- 17283505 TI - Getting a new perspective on your diabetes. Confronting fears and building motivation. PMID- 17283506 TI - Seasonal winter cooking. PMID- 17283507 TI - Update on heart disease. Evidence mounts for even lower LDL. PMID- 17283508 TI - Diabetes quiz. How much do you know about colds and flu? PMID- 17283509 TI - Diabetes information for the visually impaired. PMID- 17283510 TI - Diabetes basics. Getting a routine checkup. PMID- 17283511 TI - For parents. Preventing obesity in your child. PMID- 17283512 TI - Supermarket smarts. Frozen and canned vegetables. PMID- 17283514 TI - Diabetes resources. Finding healthy recipes. PMID- 17283513 TI - Women & diabetes. Menopause. What to expect, how to cope. PMID- 17283516 TI - Theoretical understanding of the early visual processes by data compression and data selection. AB - Early vision is best understood in terms of two key information bottlenecks along the visual pathway -- the optic nerve and, more severely, attention. Two effective strategies for sampling and representing visual inputs in the light of the bottlenecks are (1) data compression with minimum information loss and (2) data deletion. This paper reviews two lines of theoretical work which understand processes in retina and primary visual cortex (V1) in this framework. The first is an efficient coding principle which argues that early visual processes compress input into a more efficient form to transmit as much information as possible through channels of limited capacity. It can explain the properties of visual sampling and the nature of the receptive fields of retina and V1. It has also been argued to reveal the independent causes of the inputs. The second theoretical tack is the hypothesis that neural activities in V1 represent the bottom up saliencies of visual inputs, such that information can be selected for, or discarded from, detailed or attentive processing. This theory links V1 physiology with pre-attentive visual selection behavior. By making experimentally testable predictions, the potentials and limitations of both sets of theories can be explored. PMID- 17283515 TI - [An outbreak of Cyclospora cayetanensis in Medellin, Colombia]. AB - OBJECTIVE: Describing an outbreak of gastrointestinal disease in a group of 56 patients from Medellin, Colombia. METHODS: An unusual number of cases of diarrhoea appeared in April 2002 and 56 samples of stool from the same number of individuals were collected because a patient proved Cyclospora cayetanensis positive. A clinical-epidemiological survey, direct coprology, formol-ether concentration and modified Zielhs Neelsen staining were then carried out. Some food samples were also studied for parasites by direct and modified Zielh Neelsen staining. RESULTS: 55.4% (31/56) of the patients being evaluated proved positive for C. cayetanensis. 77.4% (24/31) were women and 83.9% (26/31) belonged to the University of Antioquia, 88.6% of whom were not teachers. There was no statistically significant difference between positive and negative patients for Cyclospora regarding clinical manifestations, except for dehydration which was greater in patients having cyclosporiasis. However, there was a significant difference regarding consuming salads and juice, this being greater amongst positive patients than negative ones. CONCLUSION: An outbreak of C. cayetanensis appeared in symptomatic patients being taken care of by the GIEPI group during April 2002. PMID- 17283517 TI - NAPNAP position statement on child maltreatment. PMID- 17283518 TI - [Guidelines for the diagnosis and treatment of liver fibrosis in integrative medicine practice]. PMID- 17283520 TI - Abstracts from the 1st Asia Pacific International Society for the Study of Xenobiotics Meeting. May 25-27, 2006. Jeju Island, Korea. PMID- 17283519 TI - Tables and figures: adding vitality to your article. PMID- 17283522 TI - Australian Dental Research Foundation research grant abstracts. PMID- 17283521 TI - Abstracts from the 38th Annual Meeting of the Swiss Society of Nephrology. December 7-8, 2006. Solothurn, Switzerland. PMID- 17283523 TI - Global challenge for overcoming high blood pressure. Abstracts of the 21st Scientific Meeting of the International Society of Hypertension. October 15-19, 2006. Fukuoka, Japan. PMID- 17283524 TI - Abstracts of the 60th Meeting of the Italian Society of Anatomy and Histology. September 15-17, 2006. Pavia, Italy. PMID- 17283525 TI - [All are to be treated equally, of course]. PMID- 17283526 TI - [Left main coronary artery compression in partial endocardial cushion defect. Stent implantation]. PMID- 17283528 TI - [Keep on improving the basic research of head-neck oncology]. PMID- 17283527 TI - [Investigation into "Hor Mongolian Moxibustion"]. AB - Hor, a tribe name, is a general denomination for the nomad lived north to the Great Wall, including Hun (Xiongnu), eastern Tartars (Donghu), and Xianbei, people. Hor Mongolian moxibustion is a therapeutic method discovered by those Hor people. Many types of treatments formed during its coming into being and developments, but the treatment principles came down in one continuous line. PMID- 17283529 TI - [Consideration in masked otitis media]. PMID- 17283531 TI - [Inhibited proliferation and expression of human nasopharyngeal carcinoma line induced by celecoxib in vitro]. AB - OBJECTIVE: To study the effects of celecoxib on the cell proliferation and expression of vascular endothelial growth factor (VEGF) in human nasopharyngeal carcinoma line. METHODS: 3-[ 4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) test was used to investigate the cell proliferation. Flow cytometry (FCM) was used to analyze the cell cycle arrest. Immunocytochemistry technique was to observe the expression of VEGF. RESULTS: Celecoxib inhibited the growth of nasopharyngeal carcinoma line, the cell number of G0/G1 phase increased from 62.13% to 91.35%, and the cell number of G2/M and S phase decreased from 21.59% to 3.56% and from 16.28% to 5.01%, respectively, cell cycle progression was arrested at G1/S phase. Celecoxib decreased the positive expression of VEGF in HNE-1 cells. CONCLUSIONS: Celecoxib inhibited the proliferation of nasopharyngeal carcinoma significantly and the expression of VEGF. PMID- 17283530 TI - [Specific inhibition of Raf-1 gene expression in HNE1 by RNA interference]. AB - OBJECTIVE: To silence the expression of Raf-1 gene in HNE1 cells using vector based RNA interference (RNAi) technique. METHODS: The vector containing the human U6 promoter was used for targeted gene silencing when a dsDNA oligonucleotide encoding an appropriate shRNA was ligated into the vector, and 67nt oligonucleotide fragment was inserted into the downstream of the U6 promoter. Plasmids containing different Raf-1 target sequences [ (1) pshuttle-Raf-1-a( 225), (2) pshattle-Raf-1-b ( 358) and (3) pshuttle-Raf-1-c(474)], were transfected into HNE1 cells. Expression of Raf-1 mRNA was assayed by RT-PCR. Apoptosis were determined by cytometry. RESULTS: Vector-based RNAi had advantages over antisense RNA because it could be delivered to the target cell more efficiently, and effect could last longer. Raf-1 expression could be inhibited by plasmid-expressed shRNA. Three different targeting sequences were selected from Raf-1 gene, and the inhibitory effect of pSIREN shuttle-Raf-1-b (358) was biggest. CONCLUSION: Raf-1 expression in HNE1 cells can be inhibited significantly using plasmid-based RNAi. PMID- 17283533 TI - [Analysis of surgical treatment of nasopharyngeal angiofibroma]. AB - OBJECTIVE: To study the individual surgical treatment of nasopharyngeal angiofibroma. METHODS: Between Feb. 1989 and Oct. 2004, different kinds of surgical approaches in 51 patients with angiofibromas were retrospectively analysed. Using Fisch stage: thirty three cases were in stage I and II, 22 cases via palatal approach, 11 cases via endoscopic surgery;18 cases were in stage IIN and IV, 9 cases via lateral rhinotomy approach, 4 cases via midfacial degloving approach + Lefort I approach or modified maxillotomy, 5 cases via craniofacial approach. Twenty three cases accepted the embolization of the artery which feed the tumor, 7 cases in stage IV, 8 cases in stage IlI, 5 cases in stage II, 3 cases in stage I. RESULTS: The average of blood loss was 1010 ml in operation but it became 200 - 870 ml (the average of blood loss was 485 ml) when had a selective preoperative embolization. The blood loss of none selective preoperative embolization was 500 - 3500 ml (the average of blood loss was 1600 ml), t = 7. 48, P < 0.05, the average of blood loss of selective preoperative embolization is less than the average of blood loss of none selective preoperative embolization. After 9 to 48 months of operation (the average time was 26.4 months), 8 cases recurred one time and 2 cases recurred two times. CONCLUSIONS: The preoperative embolization could reduce the amount of bleeding during operation. In patients who are in stage I and II, searching endoscopic surgery could avoid the effect on craniofacial development which traditional surgical procedure did. For patient who are in stage III and IV, midfacial degloving approach and Lefort I approach or modified maxillotomy are not only good for exclusive resection of the tumor but also have less effect on articulation and beautiful cosmetic outlook. PMID- 17283532 TI - [Relationship between the expressions of KaI1, nm23, ETS-1, VEGF and microvascular density and clinical significance in nasopharyngeal carcinoma]. AB - OBJECTIVE: To investigate the relationship between the expressions of KAI1, nm23, ETS-1, vascular endothelial growth factor (VEGF) and microvascular density (MVD) and lymph node metastasis and prognosis in nasopharyngeal carcinoma (NPC). METHODS: The Envision immunohistochemical method was used to detect the expressions of KAI1, nm23, ETS-1 and VEGF in 50 cases of non-keratinizing carcinoma (NKC) with cervical lymph node metastasis, 30 cases of NKC without cervical lymph node metastasis at the primary diagnoses and 30 cases of non-tumor nasopharyngeal tissues (NP). The microvascular density was counted by immunostaining with CD34. RESULTS: (1) The expression rates of KAI1 and nm23 protein in NKC with cervical lymph node metastasis group and without cervical lymph node metastasis group and NP group increased successively , the difference being significant (P < 0.05); The expression rates of ETS-1 and VEGF protein in NKC with cervical lymph node metastasis group and without cervical lymph node metastasis group and NP group increased successively, the difference being significant (P < 0.05). (2) In 80 NKC cases, the MVD was respectively lower in KAI1 and nm23 protein positive groups than those in the negative groups (P < 0.05); the MVD was respectively higher in ETS-1 and VEGF protein positive groups than those in the negative groups (P < 0.05 ). (3) There was significant difference between the MVD, the number of NKC without cervical lymph node metastasis cases in the single expression of KAI1 or nm23 protein and in common expression of KAI1 and nm23 protein (P < 0.05), in the same as between the single expression of ETS-1 or VEGF protein and in common expressions of ETS-1 and VEGF protein (P < 0.05). (4) There was positive correlation between the expressions of KAI1 and nm23 protein (P < 0.01), as well as between the expressions of ETS-1 and VEGF protein (P < 0.01). (5) the 5-year survival rates of the patients correlated with cervical lymph node metastasis and the expressions of KAI1, nm23, ETS-1 and VEGF proteins in NKC (P < 0.05). CONCLUSIONS: The expressions of KAI1, nm23, ETS 1 and VEGF proteins were highly related to MVD in NPC,cervical lymph node metastasis and prognosis. They might be considered to be reference indicator for evaluating the cervical lymph node metastasis and prognosis of NPC. PMID- 17283534 TI - [Bilateral facial nerve paralysis-diagnosis and treatment]. AB - OBJECTIVE: To observe the ways of diagnosis and treatment of bilateral facial nerve palsy. METHODS: Seven cases of bilateral facial nerve paralysis in 1996 - 2003 were retrospectively reviewed, and then the ways of diagnosis and therapies of these cases were analyzed. There were 6 patients with doubtless diagnosis. They were diagnosed as acute leukaemia, Vogt-Koyanagi-Harada disease (VKH), Machado-Jesoph disease, bilateral mandible fractures, Guillain-Barre syndrome, and Bell's palsy. The last one was diagnosed as Herpes zoster virus infection or Lyme disease. In all these cases, there were 4 of 5 positive cerebrospinal fluids test, 1 of 6 positive lyme antibody test, 2 of 5 positive images test, 7 of 7 EMG and Br test showed that the paralysis was peripheral palsy. All the 7 cases were treated with steroid and vitamin. RESULTS: House-Brackmann I was defined as complete recovery, after up to 2 months follow up, there were four cases got completely recovery while 2 cases incomplete recovery, and 1 case was not reacted to the therapy. CONCLUSIONS: Bilateral facial nerve paralysis was rare, and it was difficult to diagnosis and differentiation, while diagnostic mistakes would be serious. More attention should be paid to it in clinic. PMID- 17283535 TI - [Detection of specific IgE of anti-Staphylococcus aureus enterotoxins in nasal polyps and analysis theoretically about the superantigen hypothesis]. AB - OBJECTIVE: To search the evidence for the presence of superantigen of Staphylococcus aureus enterotoxin (SE) in the pathogenesis of nasal polyposis. METHODS: In a cohort of population composed of 42 cases who belonged to three groups: nasal polyposis, simple chronic rhinosinusitis (CRS), and control group without any rhinopathy, detecting the specific IgE against SE-A and B (SEA and SEB), total IgE (TIgE), eosinophilic cationic protein (ECP) of the local mucosa by means of FRAST (UniCAP system), as well as the serum TIgE, and serum anti-SEA and SEB SIgE (only in 8 cases); meanwhile the secretion culture was performed for aerobic bacteria from the middle meatus. RESULTS: There was no evidence to support that SE played as a superantigen in all mucosa samples (42 cases) and 8 cases serum samples out of the 42 patients. The range of TIgE in mucosa was 4.59 70.21 kIU/2 mg tissue protein, the mean was (17.85 +/- 14.31) kIU/2 mg tissue protein; in serum the total IgE was 7.44 - 344.00 kIU/L, the mean was (88.65 +/- 80.03) kIU/L The positive culture of Staphylococcus aureus was obtained from only 3 cases from secretion of middle meatus (1 from nasal polyps, 2 from CRS). There was no significance statistically among the three groups on the tissue fluorescence value of SIgE for SE, the means of tissue TIgE and ECP. CONCLUSIONS: No evidence was found to support the role of SE acting as a superantigen among our cases who did not have persistent asthma. It is suggested that further study and investigation is required to prove the superantigen Hypothesis in the pathogenesis of NPs. PMID- 17283536 TI - [Relationship between Staphylococcal superantigens and the dominant expression of T-cell receptor V beta gene in chronic rhinosinusitis with nasal polyp]. AB - OBJECTIVE: To analyse the relationship between superantigens produced by Staphylococcus aureus and the mRNA expression of T-cell receptor V beta region (TCR Vbeta), and to investigate the possible role of Staphylococcal superantigens in the pathogenesis of nasal polyps. METHODS: Sinonasal mucus and polyp/mucosa tissue were obtained from patients with chronic rhinosinusitis (22 patients with bilateral nasal polyps, 15 without nasal polyps) and 12 normal subjects as comparative negative controls. Mucus specimens were assayed by enzyme-linked immunosorbent assay (ELISA) for Staphylococcal exotoxins,and analyzed for the expression of TCR Vbeta genes using the technique of reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The percentages of Staphylococcus exotoxins in nasal polyps were 54.54% (21/22) for chronic rhinosinusitis with nasal polyp (CRSwNP) subjects. There were no positive results in the CRSsNP or control groups. The expressional intensity of Vbeta3 (10.02), Vbeta14 (3.54), Vbeta15 (2.39), Vbeta17 (3.48), and Vbeta20 (2.94) was increased significantly for Staphylococcal exotoxin B (SEB) positive subjects (P < 0.05). Vbeta2 (13.8) and Vbeta6. 1-3 (6.53) were significantly highly expressed for toxic shock syndrome toxin-1 (TSTf-1) positive subjects in CRSwNP group (P < 0.05). There were no dominantly used Vbeta fragments in ELISA- negative specimens. In the group of chronic rhinosinusitis without nasal polyp (CRSsNP), most of TCR Vbeta gene subfamilies demonstrated a trend toward higher expressional levels compared with those of normal controls, although there was no statistical difference (P > 0.05). CONCLUSIONS: There was relationship between Staphylococcal superantigens and the excursion of TCR Vbeta gene spectra in nasal polyp, and superantigens possibly play an important role in the pathogenesis of CRSwNP. PMID- 17283537 TI - [Display of different injuries of recurrent laryngeal nerve in laryngeal electromyography]. AB - OBJECTIVE: To study the display of different types injuries of recurrent laryngeal nerve (RLN) in laryngeal electromyography (LEMG). METHODS: LEMGs of one hundred and forty-seven patients (147 sides) with traumatic unilateral vocal cord paralysis (UVCP) were studied. After LEMGs, the RLNs exploration operations were performed. The condition of RLNs injury and laryngeal muscles was observed and recorded during the operation. RESULTS: The severe injuries of RLNs were found during operation. The types of injuries were listed as ligation (58 cases), adhesion (28 cases) and cut (61 cases). The waveform morphology of LEMG was recorded less in the patients with the RLNs cut than that in the patients with the RLN ligation or adhesion, respectively. 75.4% RLNs cut showed spontaneous waveform while 96.4% RLNs adhesion and 94.8% RLNs ligation. When the RLN was cut off, single pattern was showed oftener. When the RLN was adhered or ligated, mixed pattern was showed oftener. 92.9% RLN adhesion showed misdirect regeneration-potentials while 70.7% RLN ligation and 24.6% RLN cut. There were significant difference between two types, but the compound muscular active potential (CMAP) amplitude wasn't significantly different. Evoked amplitude could be recorded in 91.4% patients with ligation and its amplitude was (23.6 +/- 8.1)%, in 85.7% patients with adhesion and its amplitude (16.3 +/- 5.2)%, in 29.5% patients with cut and its amplitude (2.6 +/- 4.2)%. CONCLUSIONS: The display of different injuries of RLN in LEMG presents significant difference. If RLN was cut off, the CMAP might be recorded in most cases. The clinical injury of RLN often is followed by sub-clinic reinnervation. PMID- 17283538 TI - [Surgical treatment of tumors in anterior and middle skull base by modified maxillary bone disassembly procedures]. AB - OBJECTIVE: To explore the therapeutic effect of the modified maxillary bone disassembly procedures on patients with tumors in the anterior and middle skull base. METHODS: Retrospective analysis was made of patients treated with the modified maxillary bone disassembly procedures. Ten tumors in the anterior and middle skull base were resected according to the pathology, size and site of the skull base tumors including 9 benign tumors and 1 malignant tumor. RESULTS: All tumors were resected completely. All patients were followed up from 12 months to 5 years postoperatively. The complications were less and the life quality was increased. The patients with benign tumors showed no recurrence . Two patients with cerebrospinal rhinorrhea cured spontaneously after 7 days. One patient with melanoma died of brain metastase. CONCLUSIONS: It is necessary to estimate the tumors thoroughly before surgery. According to the location of the tumor, the modified maxillary bone disassembly is the nearest and harmless approach, through which the tumors can be completely excised with minimal invasiveness. The life quality is thus increased. PMID- 17283539 TI - [Expression of survivin in nasal and paranasal sinus carcinoma]. AB - OBJECTIVE: To assess the protein expression of a new inhibitor of apoptosis, survivin, and its correlation with spontaneous apoptosis, tumor clinicopathological parameters and prognosis in nasal and paranasal sinus carcinoma (NPSC). METHODS: Forty-eight patients with NPSC treated by radical operations from 1991 to 2000 were studied retrospectively. Patients included 23 females and 25 males ranging in age from 20 to 71 years. Spontaneous apoptotic cells were visualized by TUNEL accompanied by HE and PI stain. Immunohistochemistry using SP method was used to assess the expression of survivin. RESULTS: Twenty-five patients (52.08%) survived without recurrence. Recurrence or metastasis occurred in 3 patients (6.25%). Fourteen (29.17%) died from NPSC. Survivin expression was positive in 23 samples (23/48, 47.92%) but no staining was present in normal tissues beside the tumors. The expression of survivin correlated negatively with the index of apoptosis (r = - 0.393, P = 0.006). Patients with positive expression of survivin had lower apoptosis index than those with negative expression (P < 0.05). The expression of survivin in advanced stage tumors (T3 + T4) was higher than early ones (T1 + T2, P < 0.05). Patients with negative expression of survivin had much better prognosis than those with positive expression (P = 0.0346). Multivariate analyses revealed that expression of survivin and histological types were independent prognostic factors for overall survival. CONCLUSION: An inverse correlation between survivin expression and the level of spontaneous apoptosis in NPSC suggests that survivin may play an important role in the tumorgenesis of NPSC. Survivin expression may provide a novel predictive indicator for disease-free survival after surgical resection and postoperative radiochemotherapy in NPSC. PMID- 17283540 TI - [Surgical treatment of transclavicular and transsternal tumor]. AB - OBJECTIVE: To investigate surgical treatment approach of transclavicular and transsternal tumor. METHODS: Twelve cases of neck-root and mediastinum thoracis tumor subjected to cervicothoracic-combined surgical treatment were retrospectively analyzed and summarized. RESULTS: Seven cases of benign tumor survived 1-8 years after surgery. The other 5 patients were malignant tumor. Among 4 cases of metastatic squamous cell carcinoma without definite origin at neck-root site who underwent operation and routine radiotherapy, one case died of orthotopic relapse and armpit metastasis at the 16th months postoperatively; one case was lost of follow-up after surgery; another two cases showed no relapse after follow-up of 50 months and 27 months, respectively. In addition, one case of thyroid papillary carcinoma located at neck-root and mediastinum remained alive for 40 months after operation combined with radiotherapy and chemotherapy. CONCLUSIONS: The evaluation of twelve cases of transclavicular and transsternal tumor with adoption of cervicothoracic-combined surgical approach improves and develops traditional knowledge of surgical therapy of neck-root tumors. PMID- 17283541 TI - [Distribution of gentamicin in inner ear after intratympanic gentamicin injection]. AB - OBJECTIVE: To investigate uptake and accumulation of gentamicin by cells in the guinea pig inner ear after intratympanic injection using a fluorescent probe- gentamicin-Texas-red conjunction (GTTR). METHODS: Adult guinea pigs (n = 80) were administered a single dose of GTrR to the middle ear cavity through the intact membrane and survived for 12 h, 24 h, 48 h, 3 d, 4 d, 7 d, 14 d and 28 d. The distribution of GTTR in the cochlear and vestibular cells was observed after staining with phalloidin-alexa-488. Texas Red and DMSO were injected into the tympanum as control. RESULTS: Diffuse staining of gentamicin in the labyrinth was observed initially after local drug administration. At later time point the outer hair cells and sensory cells of vestibular organ were staining more densely than the support cells in the inner ear. The peak level of fluorescent density was reached 3 days after local injection. The GTTR was observed in the infracuticular zone. CONCLUSIONS: GTTR was a potential fluorescent probe to investigate the pharmacokinetics and mechanisms of gentamicin accumulation in local application. PMID- 17283542 TI - [A dopaminergic projection from the dorsal raphe nucleus to the inner ear]. AB - OBJECTIVE: To investigate the efferent pathway from the dorsal raphe nucleus to the inner ear. METHODS: Eleven adult cats weighing 2.0 - 3.0 kg were used. The animals had no middle-ear disease and their auricle reflex was sensitive to sound. They were divided into experimental group (8 cats) and control group (3 cases). The fluorescent tracer cholera toxin subunit-B (CTB) was injected into cat cochlea and the CTB-labelled neurons of dorsal raphe nucleus (DRN) were identified using an immunofluorescence technique after a survival period of 7 days. For studying other fluorescence labelling, the sections containing CTB labelled neurons were divided into four groups and incubated in antisera directed against tyrosine hydroxylase (TH), serotonin (5-HT), gamma-aminobutyric acid (GABA) and dopamine B-hydroxylase (DBH), respectively. Single-and double-labelled neurons were identified from the DRN. RESULTS: (1) A subpopulation of dorsal raphe nucleus (DRN) neurons were intensely labelled with CTB and these CTB labelled neurons were densely distributed in a dorsomedial part of the DRN; (2) Four immunolabelling, TH, 5-HT, GABA and DBH were presented throughout the DRN. Of the total population of CTB-labelled neurons, 100% were TH-labelled neurons (double labelling) and no double-stained neuron with 5-HT, GABA and DBH was observed in the DRN. CONCLUSIONS: There was a projection from DRN to the inner ear and this pathway might be a dopaminergic projection. PMID- 17283543 TI - [Three-dimensional morphological measurements of the utricle, saccule and stapes footplate]. AB - OBJECTIVE: To determine the optimal drill area on the footplate with the 3D measurements of the stapes and the vestibular end organs. METHODS: Four temporal bones were extracted from the fresh cadavers and undecalcified polymer-embedded. After serially sectioning, image processing and the 3D precisely reconstruction, a local Cartesian coordinates was established in which the tympanic surface of the footplate was supposed to be XY plane and the Z coordinate axis passed through the central point of the footplate and was vertical to the XY plane. The configurations of the utricle and saccule were delineated quantitatively, and then any distance between one point on the surface of the footplate and another point on the surface of the utricle or saccule and its orientation can be measured. RESULTS: There was a "V" shaped cleft between the utricle and the saccule. The angle of the" V" shaped cleft was 50.31 +/- 19.90 (17.00 - 68.00) degrees. The apex of the cleft directed anterosuperiorly and approached the footplate center, while beneath the posteroinferior part of the footplate was an open and deep area. The vertical distance from the center point of the footplate to the vestibular end organs was (2.20 +/- 0.548) mm, the maximum of 3.0 mm and the minimum of 1.6 mm. CONCLUSIONS: The posterior and inferior quadrant of the footplate may be the optimal drill area for the fenestra. PMID- 17283544 TI - [One case of metallic foreign body in maxillary sinus and deep neck]. PMID- 17283545 TI - [Anatomical and clinical meaning study of retro-lateral wall of antrum maxillae]. PMID- 17283546 TI - [Mice lacking the marginal cell KCNQ1 have impaired cochlear potassium cycling are profoundly deaf]. PMID- 17283547 TI - [One case of 4-months old child with juvenile hemangioma capillaries in neck]. PMID- 17283548 TI - [One case of congenital cholesteatoma of temporal squama]. PMID- 17283549 TI - [Salvage surgery for nasopharyngeal carcinoma after failure of radiotherapy]. PMID- 17283550 TI - [Diagnosis and treatment of retroglossal stenosis]. PMID- 17283551 TI - [Free perforator flaps in head and neck reconstruction]. PMID- 17283552 TI - Cytological characterization of persistent paranasal sinus secretions after endoscopic sinus surgery. AB - BACKGROUND: The aim of this study was to characterize the cellular composition of persisting sinus secretions after endoscopic sinus surgery (ESS). METHODS: Consecutive adult patients with persisting abnormal sinus secretions post-ESS were prospectively evaluated. Sinus secretions were aspirated and submitted for cytological analysis. Semiquantitative cell counts were obtained for epithelial cells (graded as present or absent), eosinophils (graded on a 4-point Likert severity scale), and neutrophils (3-point Likert scale). Prior operative histopathology from ESS and Lund CT scores were reviewed. Statistical analyses were conducted to determine the relationships between preoperative Lund score, operative histopathology, and subsequent cellular infiltrate in sinus secretions. RESULTS: Forty-three patients (mean age, 49 years) were enrolled. Epithelial cells were present in 13 (30.2%) of these individuals. Cytological eosinophilia was rated as absent in 14 (32.6%) cases, mild in 5 (11.6%) cases, moderate in 18 (41.9%) cases, and severe in 6 (14.0%) cases. Neutrophil presence was absent in 24 (55.8%) cases, present/mild in 15 (34.9%) cases, and severe in 4 (9.3%) cases. No significant correlation could be found between the presence of each of these three cell types, the presence or absence of polyps, or preoperative Lund score (all p > 0.05). Sloughed epithelial cell presence was inversely but significantly correlated with original sinus histopathological inflammation (Spearman's rho, 0.348; p = 0.04); eosinophilic cytology tended to increase with prior operative histopathology inflammatory grade but neutrophils did not. CONCLUSION: The cytological profile of persisting secretions after ESS is dominated by eosinophils and to a lesser degree neutrophils. The presence of sloughed epithelial cells may signify ongoing mucosal damage from persisting sinonasal inflammation. PMID- 17283553 TI - An animal model for the study of topical medications in sinusitis. AB - BACKGROUND: Rhinosinusitis after functional endoscopic sinus surgery often is recalcitrant to conventional medical management. Topical therapies have been popularized as a method to deliver powerful medications to diseased mucosa while limiting systemic toxicity. The aim of this study was to develop an animal model that will provide objective data in studying the efficacy of topical medications and establish a platform for translation to human clinical trials. METHODS: The maxillary sinus ostium of white rabbits was obstructed with a pledget through an antrostomy created in the anterior face of the maxilla. The sinus was inoculated with Pseudomonas aeruginosa (PAO1) and 7 days later the antrostomy was reopened, the ostial obstruction was removed, and a single lumen catheter was placed. Normal saline was irrigated through the catheter for 7 days in one group of rabbits while a control group received no irrigation. At the end of 7 days, the rabbits were euthanized, analyzed under light microscopy, and bacterial counts of the nasal lavage were determined. RESULTS: Sinusitis was confirmed in all rabbits 7 days after inoculation. Purulence, mucosal, and underlying bony inflammation persisted in both the control and the saline irrigation groups at study end. Nasal lavage bacterial counts were persistently elevated throughout the study period, indicative of bacterial viability. CONCLUSION: An animal model has been created for the study of topical medications in sinusitis. A novel catheter delivery system within an unoccluded maxillary sinus is described that will aid in efficacy studies of topical medications in the management of recalcitrant rhinosinusitis. PMID- 17283554 TI - Clinical outcomes of chronic rhinosinusitis in response to medical therapy: results of a prospective study. AB - BACKGROUND: Little information exists regarding the outcome of medical management of chronic rhinosinusitis (CRS) in adults. The aim of this study was to examine whether baseline patient demographics, symptoms, objective findings, or treatment strategies were associated with improved CRS outcomes over time. METHODS: Eighty four new patients with CRS were evaluated and medically treated for up to 12 months. Patients completed monthly health status questionnaires. The average change of symptom scores using the Sino-Nasal Outcome Test plus one additional symptom--sense of smell (SNOT-20+1)-was the primary outcome measure. RESULTS: Overall, patients experienced a modest improvement in SNOT-20+1 scores (delta = 0.61; p< 0.0001), but this did not reach the predetermined level of a clinically meaningful effect (delta = -0.80). Baseline facial pain or facial pressure was negatively associated with outcome (p = 0.048 and 0.029, respectively) and did not correlate with extent of disease by sinus CT scoring. Other factors, including nasal discharge, hyposmia, cough, nasal polyps, and sinus CT severity, did not predict outcomes. The use of either oral antibiotics or oral steroids was associated with trends toward improved outcomes only when sinus-specific symptoms alone were considered. CONCLUSION: The majority of CRS patients receiving medical treatment show modest improvement over time in SNOT-20+1 scores. Facial pain or facial pressure at entry are negatively associated with outcomes and may reflect causes other than CRS. These findings highlight the limitations of current medical treatment for CRS and the need for novel treatment strategies. PMID- 17283556 TI - Endoscopic anatomy of the parasellar region. AB - BACKGROUND: The aim of this study was to describe the endoscopic anatomy of the cavernous sinus and adjoining parasellar regions and their relationships to the sphenoid sinus. METHODS: An endoscopic transnasal transsphenoidal approach to the pituitary gland and posterior skull base was performed on three fresh frozen cadaver heads (six sides). Neural and vascular anatomic landmarks of the cavernous sinus and parasellar regions were identified and correlated with sphenoid surface anatomy. RESULTS: The posterior wall of the sphenoid sinus presents several surface landmarks allowing the identification of the sella, carotid artery, and optic nerve. Identification of the optic-carotid recess allows reflection of the internal carotid artery medially and access to the cavernous sinus. Further lateral dissection allows for easy identification of the oculomotor, trochlear, trigeminal, and abducens nerves. The ophthalmic artery then can be followed from its origin on the internal carotid artery coursing anteriorly into the orbit. The optic chiasm also can be easily identified superiorly. Posteriorly, careful dissection allows access to the basilar artery along the clivus. CONCLUSION: As endoscopic surgeons continue to expand their procedures to involve areas of the skull base outside the paranasal sinuses, knowledge of the endoscopic anatomy of the sella, parasellar, and adjacent areas is paramount. Critical landmarks are readily evident in the sphenoid sinus providing good access to neural and vascular structures of this region of the skull base. PMID- 17283557 TI - Site of attachment of inverted papilloma predicted by CT findings of osteitis. AB - BACKGROUND: The treatment of choice for sinonasal inverted papilloma (IP) is surgical resection, which typically includes identification of the site of origin with appropriate inclusion or management of this site in the surgical resection. Appropriate preoperative planning is thus of significant importance and will routinely include CT imaging and nasal endoscopy. The aim of this study was to determine whether findings of osteitis in the patients' preoperative CT images could predict the site of attachment. METHODS: This bipartite study contained both retrospective and prospective arms. For the retrospective arm, preoperative CT images of all cases were reviewed electronically in a blinded fashion by the senior author and a prediction was made for the site of attachment. The actual site of attachment as documented in the operative note was then compared with the predicted site. A similar process was followed for the prospectively acquired patients except that the site of attachment was predicted preoperatively. RESULTS: Twenty-eight retrospective and six prospective patients were identified as eligible for the study. Six retrospective patients were excluded because of incomplete data. In patients that were reviewed retrospectively, osteitis was seen in 20/22 patients and was used to correctly predict the site of attachment in 18/20 times. Of the prospectively acquired patients osteitis was seen in 5/6 patients with the site of attachment predicted in 4/5 patients. CONCLUSION: In patients in whom osteitis is detectable on the preoperative CT scan, the site of origin of the IP can be predicted with a high degree of accuracy. PMID- 17283555 TI - Chronic rhinosinusitis patients with polyps or polypoid mucosa have a greater burden of illness. AB - BACKGROUND: Recent studies suggest chronic rhinosinusitis without nasal polyposis (CRSsNP) and CRS with nasal polyposis (CRScNP) represent distinct pathological entities. The aim of this study was to determine whether patients with CRSsNP, CRScNP, and polypoid CRS could be distinguished by clinical features, radiologic extent of disease or use of medications. METHODS: New patients with CRS (n = 126) were enrolled in a prospective outcomes study. Rhinoscopic evaluation was used to classify patients. The relationship between disease phenotype and clinical parameters was examined. RESULTS: Facial pain/pressure/headache was more prevalent in CRSsNP than CRScNP (p = 0.01). Nasal obstruction and hyposmia/ anosmia were more prevalent in CRScNP than CRSsNP (p = 0.025 and 0.01, respectively). Intermediate symptom prevalence was found in polypoid CRS. Multivariate analysis confirmed that prior surgery, CT scan score, and male gender were independent predictors of polyp/polypoid phenotype. Allergic status was unrelated to CRS classification. Medication use was higher in CRScNP patients than in CRSsNP patients. CONCLUSION: Compared with CRSsNP, patients with CRScNP have a greater burden of symptoms, more prior surgery, higher CT scan scores, and greater use of medications. PMID- 17283558 TI - New bone formation in unilateral rhinosinusitis. AB - BACKGROUND: Computed tomography (CT) frequently shows abnormal bone thickening in patients with chronic rhinosinusitis. The sinus bone may be not in a static state, and remodeling occurs in response to chronic inflammation. METHODS: Ostiomeatal unit CT scans were reviewed in 29 patients with unilateral rhinosinusitis (URS) undergoing endoscopic sinus surgery. We defined new bone formation (NBF) as a remarkable bone thickening or hyperostosis of the intrinsic sinus walls in comparison with the normal side. Bony CT scores of sinus walls were expressed by the Hounsfield unit (HU) and soft tissue CT scores were measured by the Lund-Mackay system. RESULTS: Almost all of the NBF was located at the maxillary and anterior ethmoid sinuses (83.7%), and it was significantly increased in patients with higher Lund-Mackay scores (p = 0.043). The HU values were significantly different between NBF and non-NBF contralateral sides (p < 0.05). CONCLUSION: The HU may be helpful to diagnose and quantify the bone remodeling in URS. PMID- 17283559 TI - Efficacy and safety of topical combinations of ipratropium and xylometazoline for the treatment of symptoms of runny nose and nasal congestion associated with acute upper respiratory tract infection. AB - BACKGROUND: Rhinorrhea and nasal congestion are simultaneous symptoms associated with the common cold. This study investigated the efficacy and safety of a combination nasal spray of ipratropium and xylometazoline for simultaneous treatment of these symptoms. METHODS: The trial was a multicenter double-blind, parallel-group, randomized design on patients with common cold symptoms. Patients scored symptoms of runny nose and nasal congestion and recorded adverse events in a diary for up to 7 days. Patients also recorded tissue use. The five test treatments consisted of ipratropium, 0.6 mg/mL, and xylometazoline, 1.0 mg/mL; ipratropium, 0.6 mg/mL, and xylometazoline, 0.5 mg/mL; ipratropium, 0.6 mg/mL; xylometazoline, 1.0 mg/mL; and placebo solution. RESULTS: Eight hundred sixty four patients were screened and 786 patients received treatment. One day after treatment there was a clear separation between the scores for the placebo and ipratropium treatment groups for rhinorrhea and between the placebo and xylometazoline treatment groups for congestion. Both ipratropium/xylometazoline 1.0 and ipratropium/xylometazoline 0.5 treatments were superior to xylometazoline with respect to rhinorrhea (p < 0.0001) and superior to ipratropium with respect to nasal congestion scores (p < 0.001). Both the ipratropium combination treatments had significantly lower tissue use than the xylometazoline treatment group (p < 0.0001). Adverse events were distributed equally between the treatments, except mucus tinged with blood, epistaxis, nasal passage irritation, and nasal dryness, which had a higher incidence in the three groups that received medicines containing ipratropium. CONCLUSION: The results indicate that a combination medicine of ipratropium and xylometazoline is safe and effective for treatment of rhinorrhea and nasal congestion associated with common cold. PMID- 17283560 TI - Nasal mucosal temperature in relation to nasal airflow as measured by rhinomanometry. AB - BACKGROUND: The aim of this study was to measure in vivo nasal mucosal temperature and assess its relationship to nasal patency. METHODS: Nasal mucosal temperature of 30 nasal cavities was measured by means of a miniaturized thermocouple within the anterior turbinate area during respiration. Temperature values were compared with corresponding rhinomanometrical data. RESULTS: The median mucosal temperature ranged from 30.2 degrees C (range, 28.9-31.7 degrees C) after inspiration to 32.2 degrees C (range, 31.0-33.9 degrees C) after expiration. The end-inspiratory (r = -0.85) and end-expiratory mucosal temperature values (r = -0.88) negatively correlated with the rhinomanometrical data. CONCLUSION: This study supports the fact that there is a negative correlation between nasal mucosal temperature and nasal resistance. Changes in nasal patency seem to influence nasal mucosal temperature. Within this context, nasal thermoreceptors might play an important role concerning the perception of nasal patency. PMID- 17283561 TI - Impact of depression on disease-specific symptoms and quality of life in patients with chronic rhinosinusitis. AB - BACKGROUND: Depression is associated with increased symptom burden in the setting of chronic medical conditions. Studies investigating the influence of depression on the symptoms of chronic rhinosinusitis (CRS) are lacking. The purpose of this project was to establish the prevalence of depression in patients with CRS and to explore the impact of this disorder on disease-specific symptoms and general quality of life (QOL) in the preoperative and postoperative setting. METHODS: We reviewed the records of 320 consecutive patients presenting with sinonasal symptoms to our specialty sinus clinic. Patients with CRS were evaluated by nasal endoscopy, CT imaging, and validated questionnaires including the Chronic Sinusitis Survey and SF-8 Health Survey, a QOL measurement. Findings in CRS patients with depression were compared with a matched-control group of CRS patients without depression before and after endoscopic sinus surgery. RESULTS: Overall, 26% of patients presenting with sinonasal symptoms had a diagnosis of depression. After evaluation including CT imaging, 33% of the initial population was diagnosed with CRS. The prevalence of depression in these CRS patients was 25%. Disease-specific symptoms were similar between groups; however, depressed CRS patients reported significantly worse pain and energy level and difficulty with daily activities (p < 0.050) when compared with a control group of CRS patients without depression. Postoperatively, nondepressed patients showed a marked improvement in disease-specific as well as general QOL scores (p < 0.050), whereas depressed patients did not. CONCLUSION: CRS patients with and without depression have similarly poor disease-specific symptoms. However, depressed CRS patients have poorer disease-specific and overall QOL outcomes after sinus surgery. PMID- 17283562 TI - Rhinologic manifestations of ectodermal dysplasia. AB - BACKGROUND: The Ectodermal Dysplasias (ED) are a group of uncommon genetic disorders characterized by deficient development of tissues derived from ectoderm and mesoderm. Abnormalities of the respiratory epithelium prevent normal mucociliary function. We explored the prevalence and severity of sinonasal features in affected individuals. METHODS: Thirty-four subjects with ED were evaluated. A focused history and thorough nasal examination including flexible nasopharyngoscopy were performed. Patients and caregivers rated the severity of rhinologic symptoms with a standard scale. Standardized smell tests were also performed. RESULTS: The study included 21 males and 13 females whose mean age was 18.8 years (range, 4 months to 85 years). The majority (79%) had Hypohydrotic ED. Nearly half of the individuals evaluated reported moderate to severe nasal obstruction. Allergic symptoms were present in 44% of individuals whereas 41% had a history of sinusitis. Nasal concretions were significantly more troublesome in those aged 15 and under (p = 0.028). Eighteen percent had undergone sinonasal surgery. On examination, normal intranasal structures were identifiable in all patients. However, dry mucosae, prominent crusts, and concretions were found in most (79%). A deviated nasal septum was present in 23% of individuals and a saddle nose deformity in 18. Smell tests were normal for age in all subjects. CONCLUSION: Rhinologic issues are prevalent and problematic in individuals with ED. Management should focus on humidification, nasal debridement, and tailored therapy for allergic rhinitis and sinusitis. Increased awareness of the sinonasal concerns in ED will facilitate diagnosis and improve the care of these patients. PMID- 17283563 TI - Intracranial polyps in patients with Samter's triad. AB - BACKGROUND: We describe three patients with Samter's triad (nasal polyps, aspirin intolerance, and asthma) with skull base dehiscence in whom the polyps extended into the extradural space and also resulted in hypertelorism and widening of the nasal bridge. METHODS: One patient died in a road traffic accident while awaiting surgery. The other two patients underwent endoscopic resection of the polyps with a combined osteoplastic flap. RESULTS: Histology confirmed benign eosinophilic polyps with edematous stroma and a markedly thickened basement membrane. There were no complications or revision procedures. Both are symptomatically well with improvement of the hypertelorism. CONCLUSION: These cases indicate that polyps in Samter's triad may be extremely aggressive, resulting in intracranial extension. A combined endoscopic and osteoplastic flap approach is a safe and effective surgical option. PMID- 17283564 TI - Steroid injection for sinonasal polyps: the University of Virginia experience. AB - BACKGROUND: Sinonasal polyps are treated with topical steroids, systemic oral steroids, surgical excision, and intrapolyp steroid injection. Use of steroid injection is not widespread because of reported complications. The objective of this study was to evaluate the complications of intrapolyp steroid injections and compare it to the complications of surgical removal of polyps. METHODS: All patients seen between 1994 and 2003 with a diagnosis of nasal polyps were reviewed retrospectively. Demographics, complications, follow-up, and comorbidities were collected. Frequency of each treatment modality used and complications of each treatment were compared. RESULTS: Three hundred fifty-eight patients were in the study with a mean follow-up of 30 months. Respiratory comorbidities were asthma alone (35%), aspirin triad (16%), and cystic fibrosis (15%). Other comorbidities were smokers (21%). Treatment modalities were medical treatment alone (14%); medical treatment and steroid injections (19%); medical treatment and surgery (33%); and medical treatment, injections, and surgery (34%). Patients who underwent injection had fewer surgeries (p < 0.001). There was 1 minor complication associated with 1495 injections and 11 major and 16 minor complications associated with the 310 surgeries. The differences in complication rates were statistically significant (p < 0.001). There was no significant difference in demographics, follow-up, or comorbidities between patients who received injections and patients who underwent surgery. CONCLUSION: Intrapolyp steroid injection is associated with a significantly lower rate of complication than is surgical excision of sinonasal polyps. Steroid injection also may decrease the need for further surgical intervention of polyps. PMID- 17283565 TI - Once-daily administration of intranasal corticosteroids for allergic rhinitis: a comparative review of efficacy, safety, patient preference, and cost. AB - BACKGROUND: The aim of this review was to compare the efficacy, safety, patient preference, and cost-effectiveness of once-daily budesonide aqueous nasal spray (BANS), fluticasone propionate nasal spray (FPNS), mometasone furoate nasal spray (MFNS), and triamcinolone aqueous nasal spray (TANS) for treatment of allergic rhinitis (AR) in adult patients. METHODS: A MEDLINE search (1966 to January 2004) was conducted to identify potentially relevant English language articles. Pertinent abstracts from recent allergy society meetings were identified also. The medical subject heading search terms included were intranasal corticosteroid (INS), nasal steroid, BANS, MFNS, FPNS, or TANS and AR. Selected studies were randomized, controlled, comparison trials of patients with AR treated with once daily BANS, MFNS, FPNS, or TANS. RESULTS: All four INSs administered once daily were effective and well tolerated in the treatment of AR in adult patients, with similar efficacy and adverse event profiles. No differences were seen between INSs in systemic effects, except for significantly lower overnight urinary cortisol levels in healthy volunteers treated with FPNS compared with placebo. Based on sensory attributes, patients preferred BANS and TANS versus MFNS and FPNS. BANS was associated with more days of treatment per prescription at a lower cost per day for adults compared with the other INSs and is the only INS with a pregnancy category B rating. CONCLUSION: BANS, FPNS, MFNS, and TANS have similar efficacy and safety profiles. Differences in sensory attributes, documented safety during pregnancy, and cost may contribute to better patient acceptance of one INS versus another and promote better adherence to therapy. PMID- 17283566 TI - Indications for image-guided sinus surgery: the current evidence. AB - BACKGROUND: Evidence-based medicine calls for a critical evaluation of the scientific evidence for treatments of disease. This report synthesizes the available evidence supporting the indications for image guidance in sinus surgery, examining two important questions: (1) Does image-guided sinus surgery (IGSS) reduce complication rates? (2) Does IGSS improve clinical outcomes? METHODS: Primary research articles evaluated for this report were identified using appropriate search terms and a PubMed search. Two authors independently reviewed each article. Articles were assigned an evidence level based on accepted guidelines: level 1 = randomized trials, level 2 = prospective cohort studies with comparison group, level 3 = case-control studies, level 4 = retrospective case series, and level 5 = expert opinion. RESULTS: We identified 105 articles for full review and highlight 5 articles in our report. Primarily, there is expert opinion (level 5) and case series (level 4) with and without comparison groups supporting the indications for IGSS. In addition, authors point out that sample size and design issues preclude definitive randomized trials using IGSS. CONCLUSION: Although randomized trials of IGSS are not practical, ethical, or feasible, clinical experience, expert opinion, and case series support the current indications for IGSS. Studies designed to draw conclusions about the role of IGSS in decreasing major complications of sinus surgery are not possible. PMID- 17283567 TI - Outcomes of endoscopic sinus surgery for chronic rhinosinusitis associated with sinonasal polyposis. AB - BACKGROUND: The aim of this study was is to investigate the outcomes of endoscopic sinus surgery (ESS) when performed for chronic rhinosinusitis associated with sinonasal polyps. METHODS: Forty-three patients with polyps were compared with 76 patients without polyps before and after ESS. Mean follow-up was 1.5 years. Patients were analyzed prospectively based on computed tomography (CT), endoscopy, quality-of-life (QOL) assessment, and visual analog scales (VASs). Univariate analyses were performed to evaluate whether the presence of polyps was predictive of outcome. RESULTS: Patients with polyps had worse CT and endoscopy scores both pre- and postoperatively when compared with patients without polyps (p < 0.0001 for each). All patients, regardless of polyps, improved on endoscopic exam; however, patients with polyps showed a greater degree of improvement (p = 0.002). Despite this, postoperative endoscopic scores in patients with polyps were worse than those without polyps (p < 0.0001). Patients with polyps had better QOL as measured by the Chronic Sinusitis Survey (CSS) both pre- and postoperatively (p = 0.001 and 0.044, respectively). The preoperative VAS indicated that patients with polyps had increased nasal obstruction compared with patients without polyps (p = 0.002) while having less facial pain and headache (p = 0.002 and 0.005, respectively). Patients with polyps showed a greater postoperative improvement in nasal congestion (p = 0.003) but no difference in level of improvement in postoperative headache or pressure. CONCLUSION: Despite significantly worse objective testing scores, patients with polyps report significantly better QOL as measured by the CSS and less facial pain/headache as measured by VAS scores pre- and postoperatively. Polyps were not found to be predictive of QOL or endoscopic outcome. PMID- 17283568 TI - Endoscopic resection of malignant tumors of the nose and sinuses. AB - BACKGROUND: Since the introduction of endoscopic surgery, its role has been gradually extended to encompass a range of pathologies, including sinonasal tumors, facilitated by the ability to repair significant skull-base defects. However, the rarity and long natural history of malignant tumors make it difficult to accrue cohorts comparable with the established gold standard of craniofacial resection. METHODS: In this prospective cohort study, after histological confirmation and a staging imaging protocol, patients deemed suitable were offered the option of an entirely endoscopic resection as an alternative to craniofacial resection. The procedure was performed under frozen section control. The long-term follow-up protocol included both MRI and examination under anesthesia at 3- to 4-month intervals in the first 2 years and 6-month intervals thereafter. RESULTS: There were 49 patients, 26 men and 23 women, aged 34-88 years (mean, 60 years). Follow-up ranged from 6 to 126 months (mean, 36 months). Thirty-seven cases underwent radiotherapy and 14 cases underwent adjuvant chemotherapy. A wide range of pathologies included 15 cases of adenocarcinoma, 11 malignant melanomas, and 11 olfactory neuroblastomas. Hospital stay was a mean of 5 days, with no significant postoperative complications. Thirty-six patients are alive and well, 7 patients have residual disease, 4 patients are dead of disease, and 2 patients have died of intercurrent disease. Three patients have been subsequently converted to craniofacial resection. Overall survival was 88% at 5 years. CONCLUSION: These initial results suggest that endoscopic resection may provide an alternative to craniofacial resection in selected cases of sinonasal malignancy. PMID- 17283569 TI - Antiadhesive effect of the mixed solution of sodium hyaluronate and sodium carboxymethylcellulose after endoscopic sinus surgery. AB - BACKGROUND: We evaluated the clinical efficacy and safety of the mixed solution of sodium hyaluronate and sodium carboxymethylcellulose (HA-CMC) for prevention of adhesion after endoscopic sinus surgery. METHODS: Preoperative computed tomography (CT) scans were graded. At the completion of surgery, HA-CMC was applied to Merocel and repeatedly applied after the removal of Merocel. As a control, normal saline was applied. Endoscopic examination was performed postoperatively and grading was done. RESULTS: The rate of adhesion was the highest at 2 weeks postoperatively and was significantly lower in the HA-CMC treated group than the control on all postoperative days. The grouping of cases by CT scores at 2 weeks postoperatively showed lower adhesion formation with the HA-CMC treatment than the control. The safety profile of the patients was normal at 4 weeks postoperatively. CONCLUSION: HA-CMC is an efficacious and safe material in decreasing the incidence of adhesion after endoscopic sinus surgery. PMID- 17283570 TI - Transblepharoplasty approach to sequestered disease of the lateral frontal sinus with ophthalmologic manifestations. AB - BACKGROUND: Sequestered disease within the lateral extent of the frontal sinus that has eroded into the orbit through the frontal sinus floor may be difficult to address with standard ESS techniques. We describe an approach to this problem using a transblepharoplasty incision concealed in the upper eyelid crease. METHODS: Five consecutive patients with lateral frontal sinus disease involving the orbit were treated with combined ESS/transblepharoplasty approach. This used an upper lid incision and elevation of a myocutaneous flap. The preexisting dehiscence in the sinus floor was exposed, permitting extraction of fungal debris and marsupialization of the mucocele. Frontal sinusotomy was performed via combined above/below technique RESULTS: The study group included 5 patients with mean age of 50 years. Two patients had post-traumatic mucopyocele, two had allergic fungal sinusitis, and one exhibited both entities. All patients had signs of ophthalmopathy: proptosis with increased IOP (5/5), gaze restriction (5/5), and decrease in visual acuity (2/5). Ophthalmologic symptoms improved postoperatively in 5/5, but 2 patients eventually required revision endoscopic surgery. No complications occurred, and incision healing was excellent in all patients. CONCLUSION: In patients with sequestered disease of the lateral frontal sinus and ophthalmologic manifestations, the transblepharoplasty approach in combination with ESS affords excellent access while preserving cosmesis. PMID- 17283571 TI - Cavernous carotid injury during functional endoscopic sinus surgery: case presentations and guidelines for optimal management. AB - BACKGROUND: Surgery in the parasellar and paranasal regions is technically challenging because of the complex anatomic relationships between the sphenoid sinus, cavernous sinus, optic nerve, and internal carotid artery. Normal anatomic variations and pathological changes can lead to disastrous outcomes including carotid artery injury. METHODS: We present two cases of carotid injury managed at our institution. The first case involves an elective endoscopic biopsy of a clival tumor encasing a friable carotid artery. The second case features a patient transferred emergently to our medical center when brisk bleeding was encountered during functional endoscopic sinus surgery (FESS). Both carotid injuries were managed via balloon embolization with close interaction between otolaryngology and interventional radiology. We review pertinent anatomic and surgical considerations as a backdrop to a treatment algorithm for cavernous carotid hemorrhage secondary to FESS complication. RESULTS: The treatment algorithm prevented mortality and minimized morbidity in the two cases considered. CONCLUSION: Through rare, injury to the cavernous carotid during FESS can be managed successfully given efficient hemostasis and seamless cooperation among emergency room physicians, otolaryngologists, and interventional radiologists. PMID- 17283572 TI - Sinonasal epithelial cell expression of toll-like receptor 9 is decreased in chronic rhinosinusitis with polyps. AB - BACKGROUND: Innate immune recognition of pathogens by sinonasal epithelial cells may play an important role in the pathogenesis of chronic rhinosinusitis (CRS). Previous studies have indicated that toll-like receptor (TLR) mRNA is present in sinonasal mucosa, and levels of TLR9 expression are decreased in recalcitrant CRS with nasal polyps (CRSwNP). However, the cellular source and function of TLR9 in the sinonasal epithelium is not known. In this study, primary epithelial cell cultures were analyzed from control subjects and CRSwNP patients to determine the presence and function of TLR9 protein. METHODS: Primary epithelial cell cultures were established from 5 controls and 10 CRSwNP patients undergoing sinus surgery. Flow cytometry was used to confirm purity of epithelial cells and to assess expression of TLR9 protein. Epithelial cells were stimulated with TLR9 agonist, and mRNA was analyzed by real-time PCR for expression of human beta-defensin (HBD) 2 and interleukin (IL)-8. RESULTS: Flow cytometry showed TLR9 protein in 100% of epithelial cells from controls and CRSwNP patients. The level of expression was 50% lower in CRS patients than in controls. Stimulation of epithelial cells with TLR9 agonist produced a 1.5- to 9-fold increase in HBD-2 and IL-8 mRNA expression. CONCLUSION: Functional TLR9 protein is expressed by normal and diseased sinonasal epithelial cells. The level of TLR9 expression is decreased in CRSwNP patients, consistent with the previous finding of decreased TLR9 mRNA in whole sinonasal tissue. These findings suggest that impaired innate immune responses to pathogens via TLR9 on sinonasal epithelial cells may represent a critical mechanism in chronic inflammatory sinus disease. PMID- 17283573 TI - Immunolocalization of dendritic cells and pattern recognition receptors in chronic rhinosinusitis. AB - BACKGROUND: Dendritic cell (DC) activation and antigen presentation to T cells are critical to innate and adaptive immunity. Toll-like receptors (TLRs) are known to bind pathogen-associated molecular patterns in addition to sinonasally secreted surfactant proteins (SP) such as SP-A and SP-D. TLR binding is known to activate DCs. Based on these observations, we sought to establish the presence, in sinonasal mucosa, of DC and the pattern recognition receptors (PRRs), CD14, TLR2, and TLR4. METHODS: Sinonasal biopsy specimens were taken from patients with eosinophilic nonatopic nasal polyposis (n = 4), allergic fungal sinusitis (n = 1), and nondiseased patients undergoing cerebrospinal fluid leak repair or pituitary tumor resection (n = 2). Tissue samples were stained immunohistochemically for PRR (CD14, TLR2, and TLR4), mature DC marker (CD208), iDC marker (CD209), or isotype controls. RESULTS: Immature and mature DC were immunolocalized to the subepithelial stroma and ciliated epithelial surface, respectively. Diffuse staining of CD14 was observed throughout the stroma with additional staining in the ciliated epithelium. The TLR markers showed no staining in the ciliated epithelium. TLR2 primarily localized in stroma immediately deep to the ciliated epithelial surface. TLR4 immunolocalized to submucosal seromucinous gland ductal epithelium. Data from nondiseased patients were mixed, with one patient showing minimal staining of any of the tested cellular markers. CONCLUSION: This study indicates progressive DC activation and emigration of mature antigen-presenting cells from the epithelial surfaces of sinonasal mucosa. The presence of TLR known to bind SP-A and SP-D suggests a link between SP expression and immune response in sinonasal mucosa. PMID- 17283575 TI - Fos expression in the brainstem nuclei evoked by nasal air-jet stimulation in rats. AB - BACKGROUND: Noxious stimulation of the nasal mucosa may induce protective reflexes in the upper airway in rats. Previously, we have reported that nasal air jet stimulation increases the activities of the laryngeal muscles in decerebrate cats; however, the neuronal mechanism of this phenomenon still is not clarified. METHODS: After the application of nasal air-jet stimulation for 2 hours, we investigated the distribution of Fos-positive cells (FPCs) throughout the medulla compared with sham-operated rats using Fos immunoreactivity. RESULTS: FPCs in the spinal trigeminal nucleus, the parvocellular reticular nucleus, and the nucleus of the solitary tract were more frequent than the sham-operated rats. CONCLUSION: These results suggest that the afferents induced by air-jet stimulation were conveyed to these FPCs and that some of these cells might participate in the augmentation of laryngeal muscle activities during nasal air-jet stimulation. PMID- 17283574 TI - The delta F508 mutation in cystic fibrosis and impact on sinus development. AB - BACKGROUND: Cystic fibrosis (CF) patients often have widespread inflammatory paranasal sinus disease with an increased incidence of frontal, maxillary, and sphenoid hypoplasia. The most common genetic defect in CF is the delta F508 mutation. The effect of specific CF genotypes on phenotypic sinus development and infections is not well understood. The purpose of this study was to determine whether the homozygous delta F508 mutation is associated with an increased incidence of sinus hypoplasia when compared with other mutations. METHODS: This study is a retrospective review of all adult patients seen at our CF center from 1996 to 2005. Patients > or =18 years old with a CF diagnosis using genetic and sweat chloride testing and sinus CT scans were included. Frontal sinus aplasia/hypoplasia and maxillary and sphenoid sinus hypoplasia were documented using published criteria. Data collected included patient demographics, genetic mutations, and prior sinus surgeries. RESULTS: Forty-five patients were identified with an average age of 32 years (range, 18-48 years). Thirty-one patients had prior sinus surgeries. Delta F508 homozygotes (n = 25) had a significantly increased frequency of underdeveloped frontal (98%), maxillary (70%), and sphenoid (100%) sinuses (p < 0.001) when compared with other mutations (69, 8, and 50%, respectively). CONCLUSION: CF patients homozygous for the delta F508 mutation have a greater incidence of hypoplastic or underdeveloped sinuses. Whether this is secondary to an increased frequency of sinus infections or a phenotypic expression of the genetic mutation itself remains an area for further investigation. PMID- 17283576 TI - An ear for music: commentary on the cottles. PMID- 17283577 TI - Re: Nasopharyngitis is a clinical sign of laryngopharyngeal reflux. PMID- 17283578 TI - Systemic lupus erythematosus and exercise. AB - Systemic lupus erythematosus (SLE) is a rheumatic disease characterized by a variety of symptoms, especially fatigue, pain and reduced quality of life. Physical exercise is a useful tool for improving cardiovascular fitness, reducing metabolic abnormalities and fatigue and improving quality of life. However, very few studies have focused on the relationship between SLE and physical exercise. This paper reviews the main SLE symptoms that can be alleviated by exercising, as well as the results of studies seeking to analyse the exercise capacity and physical training possibilities of SLE patients. Considerations for future research are also discussed. PMID- 17283579 TI - Fine specificity of the Ro/SSA autoantibody response in relation to serological and clinical findings in 96 patients with self-reported cutaneous symptoms induced by the sun. AB - Anti-Ro/SSA assays assist the clinician in distinguishing autoimmune diseases such as Sjogrens syndrome (SS), systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus (SCLE). The objective of the study was to investigate the fine specificity of the autoantibodies in relation to clinical presentation as well as environmental and endogenous factors such as photosensitivity, smoking and immunoglobulin (Ig) levels in patients with Ro/SSA autoantibodies. Serum samples from 96 anti-Ro/SSA positive photosensitive patients were tested for autoantibody levels by enzyme-linked immunosorbent assay (ELISA) using purified recombinant Ro52 kd, Ro60 kd and La proteins as antigens. The highest levels of anti-Ro52 and anti-La were observed in patients with primary SS, and the lowest levels of anti-Ro52 in chronic cutaneous lupus erythematosus (CCLE). SCLE patients with systemic disease (SLE and/or SS) showed higher levels of anti-Ro52 than SCLE limited to the skin. A correlation between high serum levels of IgG and anti-Ro52 (P < 0.01) and between IgA and anti-Ro52 (P < 0.05) and anti-Ro60 (P < 0.05) was found. Polymorphic light eruption (PLE) was common in all diagnostic groups but did not correlate with autoantibody levels. Smoking was more common in lupus patients than in SS patients. Our findings thus propose different mechanisms for different clinical presentations of Ro/SSA positive patients. The testing of anti-Ro52 antibodies might serve as a prognostic tool in photosensitive cutaneous diseases. PMID- 17283580 TI - New immunosuppresor strategies in the treatment of murine lupus nephritis. AB - Renal involvement in systemic lupus erythematosus is a common complication that significantly worsens morbidity and mortality. Although treatment with corticosteroids and cytotoxic drugs may be useful in many cases, morbidity associated with these drugs and the relapsing nature of the disease make it necessary to develop new treatment strategies. Five-month old female NZB/W F1 mice were divided into the following groups: CYP group (n = 10), cyclophosphamide (CYP) 50 mg/kg intraperitoneally every 10 days; RAPA 1 group (n = 10) oral daily sirolimus (SRL), 1 mg/kg; RAPA 12 group (n = 13), oral daily SRL, 12mg/kg; FTY group (n = 10), oral fingolimod (FTY720), 2 mg/kg three times per week. An additional group of 13 non-treated mice were used as a control (control group). Follow-up was performed over four months. Animal survival, body weight, anti-DNA antibodies and proteinuria were determined. Kidneys were processed for conventional histology and immunofluorescence for IgG and complement. Total histological score (HS) was the sum of mesangial expansion, endocapillary proliferation glomerular deposits, extracapillary proliferation, interstitial infiltrates, tubular atrophy and interstitial fibrosis. All treated groups had lower proteinuria at the end of the follow-up with respect to the control group (P < 0.0001). Serum anti-DNA antibodies were appropriately controlled in RAPA 1 and CYP groups, but not in FTY or RAPA 12 groups. SRL and CYP arrested, and perhaps reversed almost all histological lesions. FTY720 ameliorated histological lesions but did not control mesangial expansion or interstitial infiltrates. SRL produces great improvement in murine lupus nephritis, while FTY720 seems a promising alternative if used in appropriate doses. PMID- 17283581 TI - Antinuclear antibody testing in pleural fluid for the diagnosis of lupus pleuritis. AB - We sought to determine whether measuring antinuclear antibodies (ANA) and their specificities [dsDNA, extractable nuclear antigens (ENA)] on pleural fluid may contribute to the differential diagnosis of pleural effusions. ANA were tested by indirect immunofluorescence on Hep-2 cells in the pleural fluid of 266 patients with effusions of different etiologies, including 15 lupus pleuritis. The cutoff value for diagnostic use was set at 1:160. Pleural fluid analysis of specific autoantibodies, such as anti-dsDNA and anti-ENA, was also performed if a positive ANA test was obtained. All patients with lupus pleurisy and 16 of 251 (6.4%) patients with pleural effusions secondary to other causes were ANA positive. Fifty-six percent of the positive ANAs in non-lupus pleural fluids were due to neoplasms. The pleural fluid ANA titers were low (< or = 1:80) or absent in two patients with systemic lupus erythematosus (SLE) and effusions due to other factors. Whereas ANA staining patterns in pleural fluid did not help to discriminate lupus pleuritis from non-lupus etiologies, the absence of pleural fluid anti-dsDNA or anti-ENA favored the latter. ANAs in pleural fluid provided no additional diagnostic information beyond that obtained by the measurement in serum and, therefore, these tests need not be routinely performed on pleural fluid samples. However, in patients with SLE and a pleural effusion of uncertain etiology, lack of ANAs or specific autoantibodies in pleural fluid argues against the diagnosis of lupus pleuritis. PMID- 17283582 TI - Renal damage in systemic lupus erythematosus: a comparative analysis of different age groups. AB - The objective of this study was to compare the frequency and severity of renal damage in systemic lupus erythematosus (SLE) with regard to the age of disease onset. Among 287 patients with new onset SLE diagnosed between 1991 and 2003 in our hospital, we identified those who fulfilled the American College of Rheumatology (ACR) criteria for renal involvement. Patients were categorized into childhood (age < 16 [corrected] years), adult (between 16 and 50 years) or late onset ( > or = 50 years) SLE. Clinical presentation of renal disease and cumulative renal damage as assessed by the renal domain of the Systemic Lupus International Collaborating Clinics/ACR damage index (SDI) were compared. A linear regression model was constructed to study the effect of age on renal damage. One-hundred and forty-nine patients were studied (134 women and 15 men), including 28 childhood, 107 adult and 14 late onset SLE patients. The mean age of SLE onset was 29.7 +/- 14 years. The prevalence of renal disease was 53% in childhood onset, 50% in adult onset and 58% in late onset SLE patients (P = 0.66). At renal disease presentation, late onset SLE patients had significantly lower creatinine clearance and were more likely to be hypertensive. Histological classes of nephritis and initial treatment response, however, did not differ significantly among the patients. After a mean observation of 80.3 months, 32 (21%) patients developed renal damage (renal SDI > or = 1). Late onset SLE patients had accrued more renal damage than the others. In a multiple regression model, age was not a significant determinant of renal damage after adjustment for baseline renal parameters, duration of renal disease, use of cyclophosphamide and initial treatment response. We concluded that the prevalence of renal disease was similar among SLE patients of different ages of onset. Late onset SLE patients had accrued more renal damage but age did not correlate with renal damage after adjustment for various clinical parameters. PMID- 17283583 TI - Optical coherence tomography of cutaneous lupus erythematosus correlates with histopathology. AB - Diagnosis of cutaneous forms of lupus erythematosus (LE), including chronic discoid LE (CDLE) and subacute cutaneous LE (SCLE), is usually based on characteristic clinical and histopathological findings. We aimed to visualize morphological changes in lesions of cutaneous LE using optical coherence tomography (OCT), and to correlate the OCT findings with histopathology. Six patients with CDLE and five patients with SCLE were investigated. Prior to skin biopsy, OCT assessment was performed on previously marked lesions. The images of OCT and corresponding histology were evaluated side-by-side on the PC screen. The thickening and disruption of the entrance signal in OCT images correlated with the hyperkeratosis which was observed in the histological sections. Atrophy of the epidermis, which was demonstrated by histology, could also be detected in the OCT pictures showing a thinned layer below the entrance signals. On OCT, a patchy reduction of reflectivity was observed in the upper dermis corresponding to dense patchy, partly lichenoid, lymphocytic infiltrates and oedema of the upper dermis. Furthermore, OCT images displayed increased signal-free cavities which histopathologically corresponded to dilated vessels in the upper dermis. All OCT parameters studied significantly (P < 0.05) correlated with histopathological features as indicated by coefficients of correlation ranging from 0.55 to 0.94. OCT enables to demonstrate micromorphological changes in cutaneous LE which correlate with histopathological findings. Nevertheless, the current technique does not allow one to visualize definite diagnostic features of cutaneous LE. However, OCT may be a promising method for objective monitoring of LE activity and treatment effects over time in vivo. PMID- 17283585 TI - A pilot study on tacrolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade. AB - Persistent proteinuria in patients with quiescent lupus can result from membranous lupus nephritis and/or glomerular scarring following previous flares. This pilot study examined the effects of tacrolimus over two years in six patients with membranous/inactive lupus nephritis and persistent proteinuria despite angiotensin inhibition/blockade. Tacrolimus treatment reduced proteinuria and increased serum albumin (time effect, P = 0.047 and 0.032 respectively). Compared with baseline levels, proteinuria improved by more than 50% in five patients (83.3%) and hypoalbuminaemia was corrected in four patients. The efficacy was most prominent in four patients with biopsy-proven membranous lupus nephritis, whose protienuria improved by over 80%. One patient developed biopsy proven chronic nephrotoxicity after 10 months of tacrolimus treatment, despite non-excessive blood levels. These data suggest that tacrolimus is an effective treatment for proteinuria due to membranous lupus nephritis, but should probably be reserved for patients who are refractory to other non-nephrotoxic treatments, in view of the potential risk of subclinical nephrotoxicity. PMID- 17283584 TI - Analysis of risk factors for the development of thrombotic complications in antiphospholipid antibody positive lupus patients. AB - The objective of this study was to characterize risk factors for thrombotic events in lupus patients. A total of 272 lupus patients were followed up for five years during which the presence of aPL antibodies [anticardiolipin (aCL), anti beta2-glycoprotein I (abeta2GPI) and lupus anticoagulant (LAC)] were determined, and all thrombotic incidents and antithrombotic therapy-related data were collected. At baseline, three groups were constituted, an aPL- group with 107 aPL negative patients, an aPL+ group with 81 aPL positive patients without clinical thrombosis and a secondary antiphospholipid syndrome (APS) group with 84 aPL+ patients who met the Sapporo criteria. LAC was more common in the APS than the aPL+ group (32.1% versus 9.9%, P < 0.001). The prevalence of clinical thrombotic events was significantly higher when all three types of aPL were present compared to only aCL positive cases. During follow up, aPL appeared in 7.5% of the aPL- group, and 2.8% of this group had thrombotic complications. In the aPL+ group, thrombotic events reoccurred in 1.9% of those receiving antithrombotic prophylaxis and 6.9% of those without primary prophylaxis. Despite anticoagulant therapy, thrombotic events reoccurred in 8.3% of the APS group. These findings indicate that LAC, constant and cumulative presence of aPL and previous thrombosis are positive predictors for the development of thrombotic complication in lupus patients. PMID- 17283586 TI - The lowest surviving birth weight reported in a systemic lupus erythematosus patient: a review of the literature. AB - The success rates for pregnancies in women with systemic lupus erythematosus (SLE) have improved over the years: however, pregnancy for women with active, serious, organ-threatening lupus continues to be a challenge. Preeclampsia and HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome may complicate pregnancy especially in the setting of advanced maternal age, underlying SLE and chronic renal disease. We report the pregnancy course and outcome for a 35-year old woman with active lupus nephritis at the time of conception who developed severe preeclampsia and HELLP syndrome. The infant was delivered at 26-5/7 weeks gestation, which, associated with intrauterine growth retardation, led to a birth weight of only 470 g. We have reviewed the relevant literature for similar cases of prematurity, very low birth weight, and preeclampsia in the setting of underlying lupus in Medline between 1986 and 2006. This report represents the lowest birth weight pregnancy survival in a lupus patient and the first case of a survival in the second trimester with preeclampsia and HELLP syndrome. PMID- 17283587 TI - Spontaneous splenorenal shunt in a patient with antiphospholipid syndrome: the first case reported. AB - The antiphospholipid syndrome (APS) is an autoimmune disorder, characterized by a wide spectrum of clinical manifestations. Thromboembolic events, with a greater involvement of extremities veins, are the most common features, and obstruction of abdominal vessels are sporadically reported. We present a singular case of a patient with primary APS (PAPS) that developed a spontaneous splenorenal shunt, secondary to a total portal, mesenteric and splenic vein thrombosis. Spontaneous splenorenal shunt, an uncommon circumstance reported in cirrhotic disease, to the best of our knowledge, has not been previously described in PAPS. PMID- 17283589 TI - The sex ratio of offspring of patients with systemic lupus erythematosus. PMID- 17283588 TI - Catastrophic antiphospholipid syndrome associated with malignancies (case report and review of the literature). AB - We describe a 58-year old female patient with rapid development of arterial and venous thromboembolisms, including deep vein thrombosis (DVT) in the lower limbs, recurrent cerebral infarctions and bilateral pulmonary emboli. Her laboratory data on admission showed positive anticardiolipin antibody of IgG isotype (IgG aCL) and positive anti-beta2 glycoprotein-I antibody of IgG isotype (IgG abeta2 GPI), and decreased protein C activity and protein S antigen. Systemic examinations revealed the presence of an ovarian cancer. Surgical resection was attempted, but her cancer infiltrated the pelvic wall and could not be resected. Despite treatment with unfractionated heparin followed by warfarin, she died due to recurrent episodes of cerebral infarction. This case was considered as probable catastrophic antiphospholipid syndrome (CAPS), which might be associated with ovarian cancer. Known as Trousseau's syndrome, arterial and, more commonly, venous thrombosis is a frequent complication of cancer and sometimes a harbinger of occult cancer. Our case indicates that there is an overlap between antiphospholipid syndrome (APS) and Trousseau's syndrome. It is important to bear in mind that a thrombotic event associated with cancer can be the first manifestation of CAPS. PMID- 17283591 TI - Prognosis of lupus membranous nephritis in children. PMID- 17283590 TI - A serological switching from anti-dsDNA to anti-Sm antibodies coincided with severe clinical manifestations of systemic lupus erythematosus (hemophagocytosis, profundus and psychosis). PMID- 17283592 TI - Animal use replacement, reduction, and refinement: development of an integrated testing strategy for bioconcentration of chemicals in fish. AB - When addressing the use of fish for the environmental safety of chemicals and effluents, there are many opportunities for applying the principles of the 3Rs: Reduce, Refine, and Replace. The current environmental regulatory testing strategy for bioconcentration and secondary poisoning has been reviewed, and alternative approaches that provide useful information are described. Several approaches can be used to reduce the number of fish used in the Organization for Economic Cooperation and Development (OECD) Test Guideline 305, including alternative in vivo test methods such as the dietary accumulation test and the static exposure approach. The best replacement approach would seem to use read across, chemical grouping, and quantitative structure-activity relationships with an assessment of the key processes in bioconcentration: Adsorption, distribution, metabolism, and excretion. Biomimetic extraction has particular usefulness in addressing bioavailable chemicals and is in some circumstances capable of predicting uptake. Use of alternative organisms such as invertebrates should also be considered. A single cut-off value for molecular weight and size beyond which no absorption will take place cannot be identified. Recommendations for their use in bioaccumulative (B) categorization schemes are provided. Assessment of biotransformation with in vitro assays and in silico approaches holds significant promise. Further research is needed to identify their variability and confidence limits and the ways to use this as a basis to estimate bioconcentration factors. A tiered bioconcentration testing strategy has been developed taking account of the alternatives discussed. PMID- 17283593 TI - Predicting metal toxicity in sediments: a critique of current approaches. AB - The ability to predict metal toxicity in sediments based on measurements of simple chemical parameters is not possible using currently available sediment quality guidelines (SQGs). Past evaluations of available SQGs for metals indicated little difference in their predictive abilities; however, the scientific understanding of cause-effect relationships is progressing rapidly. Today, it is clear that they can be protective of benthic ecosystem health, but single-value SQGs will be ineffective for predicting the toxicity of metals in sediments. Recent exposure-effects models and the sediment biotic ligand model both indicate that a better approach would be to have SQG concentrations, or ranges, that are applied to different sediment types. This review indicates that significant improvements in laboratory and field-based measurements, better recording of parameters that influence metal toxicity in sediments, as well as quantification of the metal exposure routes and the relative contribution of dissolved and particulate sources to toxic effects are needed to improve the power of predictive models and the overall effectiveness of SQGs for metals. Simply exposing benthic organisms to contaminated sediments and reporting effects concentrations or thresholds based on particulate metal concentrations will provide little information to aid future SQG development. For all tests, careful measurement and reporting of concentrations of particulate metal-binding phases (e.g., sulfide, organic carbon, and iron phases), metal partitioning between porewater and sediments, and porewater pH are considered as minimum data requirements. When using metal-spiked sediments, much better efforts are required to achieve sediment properties that resemble those of naturally contaminated sediments. Our current understanding of metal toxicity indicates that considerably greater information requirements will be needed to predict sublethal and chronic effects of metals, because the toxic, metabolically available concentration of metals within an organism will fluctuate over time. Based on the review of exposure and effects models, along with improved measurement of metal exposure-related parameters, the measurement of the short-term uptake rate of metals into organisms is likely to improve future models. PMID- 17283594 TI - Assessment of aquatic ecological risk and site-specific criteria of copper in San Francisco Bay, California, USA. AB - A new regression-based copper toxicity model was applied in a case study of San Francisco Bay, California, USA, to demonstrate its utility in estimating risk and site-specific water quality criteria. This was accomplished using probabilistic techniques and a simple model relating dissolved organic carbon (DOC) concentrations with the toxicity of dissolved copper to embryos of the most copper sensitive taxon (Mytilus) in the US Environmental Protection Agency's (USEPA) water quality criteria database. Similar probabilistic techniques were applied to data developed for San Francisco Bay using the USEPA's water-effect ratio (WER) methods for comparison with the DOC-based method. Based on 595 site- and date-specific DOC model observations at 26 sites in San Francisco Bay, none suggested risk of chronic toxicity. Safety factors (1/risk quotient) on average across all sites ranged from 2.4 to 9.1. Comparisons were made between 1) estimates of site-specific criteria made using the DOC method, 2) estimates of site-specific criteria made using the WER method, 3) USEPA national and California Toxics Rule criteria, and 4) region-specific criteria recommended for regulatory implementation by the Clean Estuary Partnership. The DOC- and WER based methods indicated that copper criteria for San Francisco Bay could be increased above USEPA and California Toxics Rule criteria and will retain the level of protection (> or =97%) embodied in the USEPA copper saltwater water quality criteria. The DOC method overall was more conservative (i.e., implies the need for lower criteria in the Bay) than the WER method. The DOC method suggests that the region-specific criteria being recommended for regulatory implementation would be underprotective in some areas and yet could be increased and remain protective in other areas of San Francisco Bay. PMID- 17283595 TI - Comparison of tropical and temperate freshwater animal species' acute sensitivities to chemicals: implications for deriving safe extrapolation factors. AB - Toxicity data for tropical species are often lacking for ecological risk assessment. Consequently, tropical and subtropical countries use water quality criteria (WQC) derived from temperate species (e.g., United States, Canada, or Europe) to assess ecological risks in their aquatic systems, leaving an unknown margin of uncertainty. To address this issue, we use species sensitivity distributions of freshwater animal species to determine whether temperate datasets are adequately protective of tropical species assemblages for 18 chemical substances. The results indicate that the relative sensitivities of tropical and temperate species are noticeably different for some of these chemicals. For most metals, temperate species tend to be more sensitive than their tropical counterparts. However, for un-ionized ammonia, phenol, and some pesticides (e.g., chlorpyrifos), tropical species are probably more sensitive. On the basis of the results from objective comparisons of the ratio between temperate and tropical hazardous concentration values for 10% of species, or the 90% protection level, we recommend that an extrapolation factor of 10 should be applied when such surrogate temperate WQCs are used for tropical or subtropical regions and a priori knowledge on the sensitivity of tropical species is very limited or not available. PMID- 17283596 TI - Evaluation of population-level ecological risks of dioxin-like polychlorinated biphenyl exposure to fish-eating birds in Tokyo Bay and its vicinity. AB - Population-level assessments of the ecological risks of dioxin-like polychlorinated biphenyl (PCB) exposure to fish-eating birds in Tokyo Bay and its vicinity were performed to judge the need for risk management measures to protect aquatic wildlife from dioxin-like PCB contamination. Egg mortality risk and changes in the population growth rate (lambda) in relation to the contamination levels of dioxin-like PCBs in eggs of gray heron (Ardea cinerea), great cormorant (Phalacrocorax carbo), osprey (Pandion halieaetus), and kingfisher (Alcedo atthis) were determined by integrating the results of exposure analysis, effect analysis, and a life-history model for each species. The egg mortality risks for the gray heron, great cormorant, osprey, and kingfisher populations were calculated to be 5.8, 6.8, 12, and less than 1%, respectively. The estimated lambda for those populations were calculated to be 1.061, 1.405, 1.024, and 1.131, respectively. The percentage changes in lambda for those populations were estimated to be 1.2, 2.0, 1.6, and less than 1%, respectively. Our results implied that the levels of dioxin-like PCBs observed in the Tokyo Bay area alone would not have significant population-level effects on the fish-eating bird populations. It is concluded that along with the trend toward decreasing dioxin and dioxin-like PCB levels in Tokyo Bay, no urgent need exists for risk-reduction measures to protect fish-eating bird populations against dioxin-like PCBs. PMID- 17283597 TI - Application of risk assessment and decision analysis to aquatic nuisance species. AB - The spread of nonindigenous (nonnative) species introduced into the United States is a significant and growing national problem and results in lost agricultural productivity, increased health problems, native species extinctions, and expensive prevention and eradication efforts. Thousands of nonindigenous species have either become established or spread, and introduction of aquatic nuisance species (ANS) into freshwater lakes threaten aquatic biodiversity. Expanding global trade is likely to increase the number of species that are spread across the globe, so the need to develop an approach to predict potential ANS invasions is great. Risk assessments currently being used to assess ANS risk rely on qualitative or semiquantitative information and expert opinion; thus, such approaches lack transparency and repeatability. A more quantitative approach is needed to augment the qualitative approaches currently in use. A quantitative approach with the use of the traditional ecological risk assessment (traditional ERA) framework combined with decision analysis tools was developed for assessing ANS risks in which the causative ecological risk agent is an organism rather than a chemical. This paper presents a systematic risk assessment framework that includes structured decision analysis to help organize and analyze pertinent data, state assumptions, address uncertainties in estimating the probability of an undesired ANS introduction, or spread and integrate these outputs with stakeholder values. This paper also describes when and how decision analysis tools can be used in such assessments for ANS. This framework and methodology will enable risk managers to systematically evaluate and compare alternatives and actions supporting ANS risk management and thus credibly prioritize resources. PMID- 17283598 TI - Relative toxicity and occurrence patterns of pesticide mixtures in streams draining agricultural watersheds dominated by corn and soybean production. AB - To evaluate the relative toxicity and the occurrence patterns of pesticide mixtures in streams draining agricultural watersheds, a 3-step approach was used. First, a landscape of interest was identified, defined, and isolated. Second, the relative toxicity of mixtures, on the basis of pesticide toxicity index scores, was compared with the relative toxicity of the highest individual pesticide, on the basis of highest toxicity quotient values. Third, occurrence patterns of pesticide mixtures were identified for use in follow-up mechanistic studies. The landscape of interest was identified as the corn and soybeans crop setting and concentrations of pesticides in streams within this crop setting were determined from US Geological Survey data. Pesticide toxicity index scores for individual samples were highest for the primary producers, Pseudokirchneriella subcapitata and Lemna gibba; with 95th percentile pesticide toxicity index scores of 4.7 and 1.9, respectively. The 95th percentile pesticide toxicity index score for Daphnia magna was 0.40 when a chronic sublethal endpoint was used. Pesticide toxicity index values were above the highest toxicity quotient values, indicating that consideration of mixtures does increase the estimated risk, but pesticide toxicity index scores were generally within a factor of 2 of highest toxicity quotient values, indicating that the increased risk is not large for most samples. Pesticide toxicity index scores tended to be dominated by individual pesticides and simple mixtures. Two different prioritization strategies were used to identify important mixtures for further study on the basis of potential effects on P. subcapitata. Both techniques decreased the complexity of the pesticide mixtures to consider by reducing the number of components within the identified mixtures as well as identifying a few specific combinations that constitute the majority of mixtures within the sample. Nearly all important pesticides for P. subcapitata were herbicides from 2 chemical classes: acetanilide and triazine herbicides. PMID- 17283599 TI - Probability-based estimates of site-specific copper water quality criteria for the Chesapeake Bay, USA. AB - The object of this study was to estimate site- and region-specific dissolved copper criteria for a large embayment, the Chesapeake Bay, USA. The intent is to show the utility of 2 copper saltwater quality site-specific criteria estimation models and associated region-specific criteria selection methods. The criteria estimation models and selection methods are simple, efficient, and cost-effective tools for resource managers. The methods are proposed as potential substitutes for the US Environmental Protection Agency's water effect ratio methods. Dissolved organic carbon data and the copper criteria models were used to produce probability-based estimates of site-specific copper saltwater quality criteria. Site- and date-specific criteria estimations were made for 88 sites (n = 5,296) in the Chesapeake Bay. The average and range of estimated site-specific chronic dissolved copper criteria for the Chesapeake Bay were 7.5 and 5.3 to 16.9 microg Cu/L. The average and range of estimated site-specific acute dissolved copper criteria for the Chesapeake Bay were 11.7 and 8.3 to 26.4 microg Cu/L. The results suggest that applicable national and state copper criteria can increase in much of the Chesapeake Bay and remain protective. Virginia Department of Environmental Quality copper criteria near the mouth of the Chesapeake Bay, however, need to decrease to protect species of equal or greater sensitivity to that of the marine mussel, Mytilus sp. PMID- 17283600 TI - The integration of ecological risk assessment and structured decision making into watershed management. AB - Watershed management processes continue to call for more science and improved decision making that take into account the full range of stakeholder perspectives. Increasingly, the core principles of ecological risk assessment (i.e., the development and use of assessment endpoints and conceptual models, conducting exposure and effects analysis) are being incorporated and adapted in innovative ways to meet the call for more science. Similarly, innovative approaches to adapting decision analysis tools and methods for incorporating stakeholder concerns in complex natural resource management decisions are being increasingly applied. Here, we present an example of the integration of ecological risk assessment with decision analysis in the development of a watershed management plan for the Greater Vancouver Water District in British Columbia, Canada. Assessment endpoints were developed, ecological inventory data were collected, and watershed models were developed to characterize the existing and future condition of 3 watersheds in terms of the potential risks to water quality. Stressors to water quality include sedimentation processes (landslides, streambank erosion) and forest disturbance (wildfire, major insect or disease outbreak). Three landscape-level risk management alternatives were developed to reflect different degrees of management intervention. Each alternative was evaluated under different scenarios and analyzed by explicitly examining value based trade-offs among water quality, environmental, financial, and social endpoints. The objective of this paper is to demonstrate how the integration of ecological risk assessment and decision analysis approaches can support decision makers in watershed management. PMID- 17283601 TI - Selenium effects: a weight-of-evidence approach. AB - Selenium is increasingly an issue for a wide range of mining, industrial, and agricultural operations. Appropriate methods for evaluating the impacts of selenium in aquatic ecosystems are vigorously debated in the literature. Two common approaches include the use of tissue residue guidelines and reproductive toxicity testing using field-collected fish; however, each approach on its own does not provide sufficient evidence that wild fish populations are in fact impaired. The limitations of each method are discussed, and recommendations to improve the relevance of each line of evidence are provided. A 3rd line of evidence, field measurement of fish population dynamics, is proposed and also discussed. A framework, consistent with an ecological risk assessment methodology, for the design, application, and interpretation of selenium weight of-evidence investigations is proposed. PMID- 17283602 TI - Addressing public health risks for cyanobacteria in recreational freshwaters: the Oregon and Vermont framework. AB - Toxigenic cyanobacteria, commonly known as blue green algae, are an emerging public health issue. The toxins produced by cyanobacteria have been detected across the United States in marine, freshwater and estuarine systems and associated with adverse health outcomes. The intent of this paper is to focus on how to address risk in a recreational freshwater scenario when toxigenic cyanobacteria are present. Several challenges exist for monitoring, assessing and posting water bodies and advising the public when toxigenic cyanobacteria are present. These include addressing different recreational activities that are associated with varying levels of risk, the dynamic temporal and spatial aspects of blooms, data gaps in toxicological information and the lack of training and resources for adequate surveillance. Without uniform federal guidance, numerous states have taken public health action for cyanobacteria with different criteria. Vermont and Oregon independently developed a tiered decision-making framework to reduce risk to recreational users when toxigenic cyanobacteria are present. This framework is based on a combination of qualitative and quantitative information. PMID- 17283603 TI - Environmental management with knowledge of uncertainty: a methylmercury case study. AB - In Oregon's Willamette River Basin, health advisories currently limit consumption of fish that have accumulated methylmercury to levels posing a potential health risk for humans. Under the Clean Water Act, these advisories represent an impairment of the beneficial use of fish consumption and create the requirement for a mercury total maximum daily load. A percent load reduction for total mercury was determined by comparing mercury levels in surface water to a water column guidance value linked to the protection of specified beneficial uses. In this case study, we discuss how probabilistic (Monte Carlo) methods were used to quantify uncertainty in the water column guidance value, how they provided decision makers with knowledge as to the probability of any given water column guidance value affording human health protection for methylmercury, and how this knowledge affected decisions as to a mercury load reduction for the Willamette River Basin. Through consultations with stakeholders, a water column guidance value of 0.92 ng/L (a median for higher trophic level fish) was chosen from among a suite of values of differing probabilities. The selected water column guidance value, when compared with ambient total mercury levels, indicated that a 50% probability of achieving the tissue criterion would require a load reduction of about 26%. Having and working with an explicit knowledge of uncertainty was not easy for many decision makers or stakeholders. However, such knowledge gave them more informed choices, a better understanding of what a specific choice of water column guidance value could mean in terms of achieving protectiveness, and led to a lower load reduction than suggested by a purely deterministic analysis. Nonetheless, more attention must be given to developing management, communication, and regulatory frameworks that can effectively use the greater knowledge of uncertainty afforded by probabilistic methods. PMID- 17283604 TI - Field studies in pesticide registration: questioning the answers. AB - The principal conclusion of a workshop in October 2005 at RIVM (Bilthoven, The Netherlands) on the assessment of field studies with pesticides for authorization is that the lack of a definition of acceptability of effects is recognized as a problem by all stakeholders: Industry, risk assessors, and regulators. Because of this lack of definition in the legislation, it is unclear what critical effect values should be assessed in field studies. Despite the extensive documentation on field study performance, the decision making is not based on justifiable scientific opinions or publicly shared values but on technical limitations of the test design instead. In the workshop, research was identified that should result in a scientific basis for value judgments applied in decision making. PMID- 17283605 TI - Neurophysiological and anatomical plasticity in the adult sensorimotor cortex. AB - Evidence supporting the plastic capacity of the adult cortex is abundant. Changes have been associated with exposure to enriched environments, learning, peripheral lesions and central lesions. The initial loss of function caused by a lesion is generally followed by a certain amount of recovery that is believed to be due, at least in part, to adaptive plasticity. In particular, the reorganization of cortical representational maps has been associated with improvement of performance. Therefore, areas undergoing such reorganization following lesions are generally assumed to participate in the recovery. We review evidence demonstrating the remodeling of representational maps of the forelimb in adult cortex and the structural plasticity that has been coupled with it. A particular emphasis is paid to non-human primate studies and stroke. PMID- 17283606 TI - Cytoskeletal transport in the aging brain: focus on the cholinergic system. AB - There is now compelling evidence for the aging-related breakdown of cytoskeletal support in neurons. Similarly affected are the principal components of the intracellular microtubule system, the transport units involved in active shuttle of organelles and molecules in an antero- and retrograde manner, and the proteins stabilizing the cytoskeleton and providing trophic support. Here, we review the basic organization of the cytoskeleton, and describe its elements and their interactions. We then critically assess the role of these cytoskeletal proteins in physiological aging and aging-related malfunction. Our focus is on the microtubule-associated protein tau, for which comprehensive investigations suggest a critical role in neurodegenerative diseases, for instance tauopathies. These diseases frequently lead to cognitive decline and are often paralleled by reductions in cholinergic neurotransmission. We propose this reduction to be due to destabilization of the cytoskeleton and protein transport mechanisms in these neurons. Therefore, maintenance of the neuronal cytoskeleton during aging may prevent or delay neurodegeneration as well as cognitive decline during physiological aging. PMID- 17283607 TI - The role of the extracellular signal-regulated kinase pathway in memory encoding. AB - All types of memory depend on the integrated activity of various brain structures and neurotransmitter systems and involve more than one receptor, signal transduction pathway and postsynaptic mechanism. The components of the extracellular signal regulated kinases-1 and -2 (ERK1/2) signal transduction pathways are ubiquitous and well conserved protein kinases involved in relaying extracellular signals into intracellular responses, and are involved in the mechanisms of synaptic plasticity, learning and memory. ERK activation is required for the full expression of long-term potentiation (LTP), the principal cellular mechanism thought to underlie neuronal plasticity. Furthermore, ERK is activated in and is necessary for the development of several forms of memory, such as fear conditioning, conditioned taste aversion memory, spatial memory, step-down inhibitory avoidance and object recognition memory. ERK activation is secondary to neurotransmitter release and activation of the forebrain cholinergic neurons during and immediately after acquisition of an inhibitory avoidance response, revealed by increased release of acetylcholine (ACh), which in turn activates ERK in neurons located in the medial prefrontal cortex and ventral hippocampus. Increased release of ACh and ERK activation are events mechanistically related to each other, as demonstrated by the use of scopolamine, a muscarinic receptor antagonist, and by inhibitors of ERK activation, which blocked memory encoding and ERK activation. A critical function of activated ERK downstream of the increased ACh release occurring during learning is to promote cellular integration of divergent downstream effectors which may trigger different responses, depending upon which subsets of scaffolding anchors, target proteins and regulatory phosphatases are involved. The hope is that by studying how ERK is activated by different neurotransmitter systems and the ensuing downstream cellular modifications, the molecular basis of memory will be ultimately understood. PMID- 17283608 TI - The role of neurotrophins and insulin on tau pathology in Alzheimer's disease. AB - Alterations in the structure and function of tau protein is the primary pathology of a variety of neurodegenerative diseases, including Alzheimer's disease (AD). In these diseases, hyperphosphorylated tau protein forms aggregates which are deposited in the somadendritic regions of the neurons in the central nervous system. This series of events is toxic to neurons, and plays a crucial role in disease development. However, the events leading to the deregulation of tau protein in AD are not clear. Recently, there has been much research into the possible roles of neurotrophic factors in AD. AD brain exhibits changes in levels of different neurotrophic factors, including brain-derived neurotrophic factor and nerve growth factor. These neurotrophic factors are known to be important for the proper functioning of neurons, and their deregulation may play an important role in AD disease progression. Of particular interest, these neurotrophic factors may play a role in the regulation and proper function of tau protein. In this review, the roles of neurotrophic factors in AD and in the regulation of tau protein are discussed. PMID- 17283609 TI - Functional and neural mechanisms of embodiment: importance of the vestibular system and the temporal parietal junction. AB - Embodiment, the sense of being localized within one's physical body, is a fundamental aspect of the self. Recent research shows that self and body processing as well as embodiment require distinct brain mechanisms. Here, we review recent clinical and neuroimaging research on multisensory perception and integration as well as mental imagery, pointing out their importance for the coding of embodiment at the temporo-parietal junction (TPJ). Special reference is given to vestibular mechanisms that are relevant for self and embodiment and to methods that interfere experimentally with normal embodiment. We conclude that multisensory and vestibular coding at the TPJ mediates humans' experience as being embodied and spatially situated, and argue that pathologies concerning the disembodied self, such as out-of-body experience or other autoscopic phenomena, are due to deficient multisensory integration at the TPJ. PMID- 17283610 TI - Prophylaxis and treatment of pregnant women for emerging infections and bioterrorism emergencies. AB - Emerging infectious disease outbreaks and bioterrorism attacks warrant urgent public health and medical responses. Response plans for these events may include use of medications and vaccines for which the effects on pregnant women and fetuses are unknown. Healthcare providers must be able to discuss the benefits and risks of these interventions with their pregnant patients. Recent experiences with outbreaks of severe acute respiratory syndrome, monkeypox, and anthrax, as well as response planning for bioterrorism and pandemic influenza, illustrate the challenges of making recommendations about treatment and prophylaxis for pregnant women. Understanding the physiology of pregnancy, the factors that influence the teratogenic potential of medications and vaccines, and the infection control measures that may stop an outbreak will aid planners in making recommendations for care of pregnant women during large-scale infectious disease emergencies. PMID- 17283611 TI - Emerging infections and pregnancy. AB - A key component of the response to emerging infections is consideration of special populations, including pregnant women. Successful pregnancy depends on adaptation of the woman's immune system to tolerate a genetically foreign fetus. Although the immune system changes are not well understood, a shift from cell mediated immunity toward humoral immunity is believed to occur. These immunologic changes may alter susceptibility to and severity of infectious diseases in pregnant women. For example, pregnancy may increase susceptibility to toxoplasmosis and listeriosis and may increase severity of illness and increase mortality rates from influenza and varicella. Compared with information about more conventional disease threats, information about emerging infectious diseases is quite limited. Pregnant women's altered response to infectious diseases should be considered when planning a response to emerging infectious disease threats. PMID- 17283612 TI - Health consequences of child marriage in Africa. AB - Despite international agreements and national laws, marriage of girls <18 years of age is common worldwide and affects millions. Child marriage is a human rights violation that prevents girls from obtaining an education, enjoying optimal health, bonding with others their own age, maturing, and ultimately choosing their own life partners. Child marriage is driven by poverty and has many effects on girls' health: increased risk for sexually transmitted diseases, cervical cancer, malaria, death during childbirth, and obstetric fistulas. Girls' offspring are at increased risk for premature birth and death as neonates, infants, or children. To stop child marriage, policies and programs must educate communities, raise awareness, engage local and religious leaders, involve parents, and empower girls through education and employment. PMID- 17283613 TI - Anatidae migration in the western Palearctic and spread of highly pathogenic avian influenza H5NI virus. AB - During the second half of 2005, highly pathogenic avian influenza (HPAI) H5N1 virus spread rapidly from central Asia to eastern Europe. The relative roles of wild migratory birds and the poultry trade are still unclear, given that little is yet known about the range of virus hosts, precise movements of migratory birds, or routes of illegal poultry trade. We document and discuss the spread of the HPAI H5N1 virus in relation to species-specific flyways of Anatidae species (ducks, geese, and swans) and climate. We conclude that the spread of HPAI H5N1 virus from Russia and Kazakhstan to the Black Sea basin is consistent in space and time with the hypothesis that birds in the Anatidae family have seeded the virus along their autumn migration routes. PMID- 17283614 TI - Review of aerosol transmission of influenza A virus. AB - In theory, influenza viruses can be transmitted through aerosols, large droplets, or direct contact with secretions (or fomites). These 3 modes are not mutually exclusive. Published findings that support the occurrence of aerosol transmission were reviewed to assess the importance of this mode of transmission. Published evidence indicates that aerosol transmission of influenza can be an important mode of transmission, which has obvious implications for pandemic influenza planning and in particular for recommendations about the use of N95 respirators as part of personal protective equipment. PMID- 17283616 TI - Targeted social distancing design for pandemic influenza. AB - Targeted social distancing to mitigate pandemic influenza can be designed through simulation of influenza's spread within local community social contact networks. We demonstrate this design for a stylized community representative of a small town in the United States. The critical importance of children and teenagers in transmission of influenza is first identified and targeted. For influenza as infectious as 1957-58 Asian flu (=50% infected), closing schools and keeping children and teenagers at home reduced the attack rate by >90%. For more infectious strains, or transmission that is less focused on the young, adults and the work environment must also be targeted. Tailored to specific communities across the world, such design would yield local defenses against a highly virulent strain in the absence of vaccine and antiviral drugs. PMID- 17283615 TI - Susceptibility of North American ducks and gulls to H5N1 highly pathogenic avian influenza viruses. AB - Since 2002, H5N1 highly pathogenic avian influenza (HPA1) viruses have been associated with deaths in numerous wild avian species throughout Eurasia. We assessed the clinical response and extent and duration of viral shedding in 5 species of North American ducks and laughing gulls (Larus atricilla) after intranasal challenge with 2 Asian H5N1 HPAI viruses. Birds were challenged at approximately equal to 10 to 16 weeks of age, consistent with temporal peaks in virus prevalence and fall migration. All species were infected, but only wood ducks (Aix sponsa) and laughing gulls exhibited illness or died. Viral titers were higher in oropharyngeal swabs than in cloacal swabs. Duration of viral shedding (1-10 days) increased with severity of clinical disease. Both the hemagglutination-inhibition (HI) and agar gel precipitin (AGP) tests were able to detect postinoculation antibodies in surviving wood ducks and laughing gulls; the HI test was more sensitive than the AGP in the remaining 4 species. PMID- 17283617 TI - Seroprevalence of hepatitis E virus infection, rural southern People's Republic of China. AB - Genotype 4 hepatitis E virus (HEV) is the dominant cause of hepatitis E in the People's Republic of China; swine are the principal reservoir. Our study was conducted in 8 rural communities of southern China, where families keep pigs near their homes. Phylogenetic analysis showed that 23 of 24 concurrent virus isolates from this region are genotype 4 strains. Among the study populations, immunoglobulin G anti-HEV seroprevalence accumulated with age at approximately equal to 1% per year for persons < or =60 years of age. After age 30 years, seroprevalence increased at higher rates for male than for female study participants. The overall seroprevalence was 43% (range 25%-66%) among the communities. Infection rates were higher for participants between 25 and 29 years of age. The results suggest that HEV infection probably has been endemic in southern China for at least 60 years, with swine being the principal reservoir of human HEV infection in recent years. PMID- 17283618 TI - Spatiotemporal analysis of invasive meningococcal disease, Germany. AB - Meningococci can cause clusters of disease. Specimens from 1,616 patients in Germany obtained over 42 months were typed by serogrouping and sequence typing of PorA and FetA and yielded a highly diverse dataset (Simpson's index 0.963). A retrospective spatiotemporal scan statistic (SaTScan) was applied in an automated fashion to identify clusters for each finetype defined by serogroup variable region (VR) VR1 and VR2 of the PorA and VR of the FetA. A total of 26 significant clusters (p< or =0.05) were detected. On average, a cluster consisted of 2.6 patients. The median population in the geographic area of a cluster was 475,011, the median cluster duration was 4.0 days, and the proportion of cases in spatiotemporal clusters was 4.2%. The study exemplifies how the combination of molecular finetyping and spatiotemporal analysis can be used to assess an infectious disease in a large European country. PMID- 17283619 TI - Schistosomiasis among travelers: new aspects of an old disease. AB - Schistosomiasis is increasingly encountered among travelers returning from the tropics; signs and symptoms of travelers may differ from those of local populations. During 1993-2005, schistosomiasis was diagnosed in 137 Israeli travelers, most of whom were infected while in sub-Saharan Africa. Clinical findings compatible with acute schistosomiasis were recorded for 75 (66.4%) patients and included fever (71.3%), respiratory symptoms (42.9%), and cutaneous symptoms (45.2%). At time of physical examination, 42 patients (37.1%) still had symptoms of acute schistosomiasis, chronic schistosomiasis had developed in 23 (20.4%), and 48 (42.5%) were asymptomatic. Of patients who were initially asymptomatic, chronic schistosomiasis developed in 26%. Diagnosis was confirmed by serologic testing for 87.6% of patients, but schistosome ova were found in only 25.6%. We conclude that acute schistosomiasis is a major clinical problem among travelers, diagnostic and therapeutic options for acute schistosomiasis are limited, and asymptomatic travelers returning from schistosomiasis-endemic areas should be screened and treated. PMID- 17283620 TI - Gastroenteritis and transmission of Helicobacter pylori infection in households. AB - The mode of transmission of Helicobacter pylori infection is poorly characterized. In northern California, 2,752 household members were tested for H. pylori infection in serum or stool at a baseline visit and 3 months later. Among 1,752 person considered uninfected at baseline, 30 new infections (7 definite, 7 probable, and 16 possible) occurred, for an annual incidence of 7% overall and 21% in children <2 years of age. Exposure to an infected household member with gastroenteritis was associated with a 4.8-fold (95% confidence interval [CI] 1.4 17.1) increased risk for definite or probable new infection, with vomiting a greater risk factor (adjusted odds ratio [AOR] 6.3, CI 1.6-24.5) than diarrhea only (AOR 3.0, p = 0.65). Of probable or definite new infections, 75% were attributable to exposure to an infected person with gastroenteritis. Exposure to an H. pylori-infected person with gastroenteritis, particularly vomiting, markedly increased risk for new infection. PMID- 17283621 TI - Serotype competence and penicillin resistance in Streptococcus pneumoniae. AB - From 2003 to 2005, we prospectively collected 118 isolates of pneumococci belonging to 7 serotypes to investigate their competence under the influence of the synthetic competence-stimulating peptides. The degree of competence of the various serotypes differed significantly. Serotype 6B had the highest competence, followed by serotypes 14, 19F, 9V, 23F, 3, and 18C. Isolates belonging to serotype 6B had greater genetic diversity than isolates belonging to serotype 3, which has high genetic clustering. Isolates belonging to serotypes 3 and 18C that were 100% sensitive to penicillin were significantly less competent than isolates belonging to serotypes 6B, 14, 19F, 9V, and 23F, which were frequently resistant to penicillin. Under the 7-valent pneumococcal conjugate vaccine program, enhanced molecular surveillance of virulent clones with higher competence to detect serotype switching will become more important. PMID- 17283622 TI - Staphylococcus aureus-associated skin and soft tissue infections in ambulatory care. AB - To describe the number and treatment of skin and soft tissue infections likely caused by Staphylococcus aureus in the United States, we analyzed data from the 1992-1994 and 2001-2003 National Ambulatory Medical Care Surveys and National Hospital Ambulatory Medical Care Surveys. Each year, data were reported by an average of 1,400 physicians, 230 outpatient departments, and 390 emergency departments for 30,000, 33,000, and 34,000 visits, respectively. During 2001 2003, the number of annual ambulatory care visits for skin and soft tissue infections was 11.6 million; the visit rate was 410.7 per 10,000 persons. During the study period, rates of overall and physician office visits did not differ; however, rates of visits to outpatient and emergency departments increased by 59% and 31%, respectively. This increase may reflect the emergence of community acquired methicillin-resistant S. aureus infections. PMID- 17283623 TI - Humans as reservoir for enterotoxin gene--carrying Clostridium perfringens type A. AB - We found a prevalence of 18% for enterotoxin gene-carrying (cpe+) Clostridium perfringens in the feces of healthy food handlers by PCR and isolated the organism from 11 of 23 PCR-positive persons by using hydrophobic grid membrane filter-colony hybridization. Several different cpe genotypes were recovered. The prevalence was 3.7% for plasmidial IS1151-cpe, 2.9% for plasmidial IS1470-like cpe, 0.7% for chromosomal IS1470-cpe, and 1.5% for unknown cpe genotype. Lateral spread of cpe between C. perfringens strains was evident because strains from the same person carried IS1470-like cpe but shared no genetic relatedness according to pulsed-field gel electrophoresis analysis. Our findings suggest that healthy humans serve as a rich reservoir for cpe+ C. perfringens type A and may play a role in the etiology of gastrointestinal diseases caused by this organism. The results also indicate that humans should be considered a risk factor for spread of C. perfringens type A food poisoning and that they are a possible source of contamination for C. perfringens type A food poisoning. PMID- 17283625 TI - VEB-1 in Achromobacter xylosoxidans from cystic fibrosis patient, France. PMID- 17283624 TI - Clostridium difficile PCR ribotypes in calves, Canada. AB - We investigated Clostridium difficile in calves and the similarity between bovine and human C. difficile PCR ribotypes by conducting a case-control study of calves from 102 dairy farms in Canada. Fecal samples from 144 calves with diarrhea and 134 control calves were cultured for C. difficile and tested with an ELISA for C. difficile toxins A and B. C. difficile was isolated from 31 of 278 calves: 11 (7.6%) of 144 with diarrhea and 20 (14.9%) of 134 controls (p = 0.009). Toxins were detected in calf feces from 58 (56.8%) of 102 farms, 57 (39.6%) of 144 calves with diarrhea, and 28 (20.9%) of 134 controls (p = 0.0002). PCR ribotyping of 31 isolates showed 8 distinct patterns; 7 have been identified in humans, 2 of which have been associated with outbreaks of severe disease (PCR types 017 and 027). C. difficile may be associated with calf diarrhea, and cattle may be reservoirs of C. difficile for humans. PMID- 17283626 TI - Molecular characterization of tickborne relapsing fever Borrelia, Israel. PMID- 17283627 TI - Fatal avian influenza A H5N1 in a dog. PMID- 17283629 TI - Genotype III Saint Louis encephalitis virus outbreak, Argentina, 2005. AB - Twenty-six years after it was last detected, Saint Louis encephalitis virus (SLEV) genotype III reemerged in 2005 in C6rdoba, Argentina, where it caused an outbreak. Two genotype III SLEV strains were isolated from Culex quinquefasciatus. A 71.43% prevalence for neutralizing antibodies was found in domestic fowl in the homestead of a patient with encephalitis. PMID- 17283630 TI - Human parainfluenza type 4 infections, Canada. PMID- 17283628 TI - Reemergence of dengue virus type 4, French Antilles and French Guiana, 2004-2005. PMID- 17283631 TI - Methicillin resistant Staphylococcus aureus at canoe camp. PMID- 17283632 TI - Knowledge, attitudes, and practices of avian influenza, poultry workers, Italy. PMID- 17283633 TI - Avian influenza H5N1 screening of intensive care unit patients with community acquired pneumonia. PMID- 17283634 TI - The study transplacental chikungunya virus antibody kinetics, Thailand. AB - Antibodies to chikungunya virus were detected by hemagglutination-inhibition assay in 33.6% of 2,000 infants' cord sera at delivery. Follow-up of 24 seropositive infants showed that the half-life of antibody persistence was 35.5 days. Chikungunya virus infection is common in Thailand, and routine use of diagnostic assays is needed. PMID- 17283635 TI - Food markets with live birds as source of avian influenza. AB - A patient may have been infected with highly pathogenic avian influenza virus H5N1 in Guangzhou, People's Republic of China, at a food market that had live birds. Virus genes were detected in 1 of 79 wire cages for birds at 9 markets. One of 110 persons in the poultry business at markets had neutralizing antibody against H5N1. PMID- 17283636 TI - The study recurrent tuberculosis and exogenous reinfection, Shanghai, China. AB - Of 52 patients with recurrent tuberculosis in Shanghai, People's Republic of China, 32 (61.5%) had isolates in which genotype patterns of Mycobacterium tuberculosis differed between first and second episodes. This result indicates that exogenous reinfection is common in an area with a high incidence of tuberculosis. PMID- 17283638 TI - Sexual health in art and science. PMID- 17283637 TI - Identical genotype B3 sequences from measles patients in 4 countries, 2005. AB - Surveillance of measles virus detected an epidemiologic link between a refugee from Kenya and a Dutch tourist in New Jersey, USA. Identical genotype B3 sequences from patients with contemporaneous cases in the United States, Canada, and Mexico in November and December 2005 indicate that Kenya was likely to have been the common source of virus. PMID- 17283639 TI - Panton-Valentine leukocidin-producing Staphylococcus aureus. PMID- 17283640 TI - Chikungunya fever, Hong Kong. PMID- 17283641 TI - Screening laboratory requests. PMID- 17283642 TI - Malaria outbreak in troops returning from French Guiana. PMID- 17283643 TI - Plasmodium vivax malaria relapses after primaquine prophylaxis. PMID- 17283644 TI - Avian influenza and US tv news. PMID- 17283645 TI - Resistance to dihydroartemisinin. PMID- 17283646 TI - Real-time PCR for Francisella tularensis types A and B. PMID- 17283647 TI - Concurrent plasmodium vivax malaria and dengue. PMID- 17283649 TI - Influenza-related death rates for pregnant women. PMID- 17283648 TI - Rickettsia parkeri in Uruguay. PMID- 17283650 TI - Women caring for children in "the floating world". PMID- 17283651 TI - [Benzo[c][2,7]naphthyridine-2-yl-, 5-yl- and 2,5-diyl novaldiamines--synthesis and investigation of anti-malarial activity]. AB - The 2,5-dichlorobenzo[c][2,7]naphthyridine 6 was synthesized starting from the 2 pyridone 1 in four or five steps, respectively. The 5-yl amine 7 and the 2,5-diyl amines 8 and 9 were isolated by the reaction of compound 6 with the novaldiamine base. Starting with the reaction of the 6-chloropyridine 3 with the novaldiamine base to yield the 6-aminopyridine 11, the 2-yl amine 13, isomeric to 7, was obtained. Compounds 7-13 were tested for in vitro antimalarial activity using a chloroquine sensitive and resistant Plasmodium falciparum strain. The highest activity was shown by 8 with IC50 values of 90 nM and 190 nM, respectively. PMID- 17283652 TI - Determination and assay validation of the bioactive sesquiterpene lactone xanthatin isolated from Xanthium cavanillesii using capillary electrophoresis. AB - This study describes the development and validation of a method for quantification of the antiulcer experimental drug xanthatin in tablets by capillary electrophoresis (CE). Solid oral dosage forms based on xanthatin were designed and assayed on rats. A CE methodology was developed; the parameters evaluated were: background electrolyte composition, concentration and pH, applied voltage and sample preparation. The method was validated in terms of range of linearity, limits of detection (LOD) and quantification (LOQ), accuracy, precision and selectivity and then applied to the pharmaceutical dosage forms. Xanthatin determination was carried out in less than 3 min with a 20 mM sodium tetraborate buffer, pH 9.20. Drug concentration per tablet found was 2.97 +/- 0.2 mg. Calibration plots were linear over at least three orders of magnitude of analyte concentrations, LOD and LOQ were 7.6 and 26 microg mL(-1) respectively. For accuracy evaluation a recovery test was performed, the values being better than 98.6%. With respect to precision, the results obtained were better than 1.02 RSD% (repeatability) and 1.54% (intermediate precision). After the manufacturing process the resulting tablets were biologically active. The methodology developed is useful, simple and rapid for xanthatin determination in tablets. PMID- 17283653 TI - Simultaneous determination of diallyl trisulfide and diallyl disulfide in rat blood by gas chromatography with electron-capture detection. AB - A simple, rapid and sensitive method has been developed and validated for the simultaneous quantification of diallyl trisulfide (DATS) and diallyl disulfide (DADS) in rat blood by gas chromatography with electron-capture detection. The analytes were prevented from degradation by addition of acetonitrile and extraction with hexane before gas chromatographic separation. Two calibration curves for DATS were linear over the range of 10-500 ng/mL and 0.2-20 microg/mL, with typical r values of 0.9989 and 0.9993, respectively. Similarly, two calibration curves for DADS were linear in the concentration range of 50-5000 ng/mL and 1-30 microg/mL, with typical r values of 0.9989 and 0.9983, respectively. The limit of detection was less than 10 ng/mL for DATS and 50 ng/mL for DADS, and the assay was highly reproducible, considering the intra-, inter day relative standard deviations (R.S.D.) below 12%. The developed procedure was successfully applied for the evaluation of the pharmacokinetics of garlic oil following iv administration at a single dose (10 mg) of garlic oil in rats. The results show that the developed method is suitable for pharmacokinetic and therapeutic purposes of DATS and DADS. PMID- 17283654 TI - Assay of terpene alcohols in pharmacopoeial essential oils by micellar electrokinetic capillary chromatography (MEKC). AB - Micellar electrokinetic capillary chromatography (MEKC) was used to separate and determine terpene alcohols of wide occurrence in herbal extracts and essential oils, namely eugenol, linalool, geraniol, citronellol and thymol. In the present paper sodium dodecyl sulfate (SDS) has been used as a micelle-forming additive to the CZE background electrolytes. Effects of SDS concentration, buffer type, its pH and concentration, addition of organic solvents on the migration times and separation efficiency were investigated. The optimal electrolyte system consisted of 20 mM TAPSO and 30 mM SDS in aqueous 10% (v/v) acetonitrile of pH 7.5 (adjusted by the addition of TRIS). The separation capillary was a fused silica tube (50 microm I. D., total length 75 cm, 42 cm effective length) maintained at 25 degrees C. The separations were performed at the applied voltage of 20 kV. Samples were injected hydrodynamically at a pressure of 50 mbar for 6 s. Detection was carried out at 200 nm. The calibration curves were rectilinear for 50-200 mg l(-1) (for eugenol, thymol and geraniol) and 100-400 mg l(-1) (for linalool and citronellol). The limits of detection varied between 5 mg l(-1) (for thymol) and 16 mg l(-1) (for linalool). The devised MEKC method was employed for the determination of the cited terpene alcohols as major quality-affecting constituents in commercial pharmacopoeial essential oils such as Geranii etheroleum, Caryophylli floris etheroleum, Lavandulae etheroleum and Thymi etheroleum. The results agreed well with those of a reference gas chromatographic method. PMID- 17283655 TI - Structural studies of racecadotril and its process impurities by NMR and mass spectroscopy. AB - Three unknown impurities in racecadotril bulk drug at levels below 0.5% were detected by simple reverse phase isocratic high performance liquid chromatography (HPLC). Structures for these impurities were proposed by molecular ion information and their fragmentation pattern obtained by LC-MS and these impurities were confirmed by NMR spectroscopy. The impurities I, II and III were characterized as benzyl 2-methyl carboximido acetate, benzyl 2-phenyl ethyl carboximido acetate, and benzyl 2-(1-benzyl vinyl carboximido) acetate. These structures were further confirmed by co-injecting of synthetic standards of impurities with racecadotril. The mechanism of the formation of these process related impurities is discussed. PMID- 17283656 TI - Crystal structure of indapamide determined from powered diffraction data. AB - Indapamide is used in the treatment of hypertension. In the European Pharmacopoeia it is specified that indapamide may contain up to 3 wt.% of water. On the basis of the results of thermal (TGA, DSC), DVS and X-ray powder diffraction analyses it has been supposed that this feature arises from the fact that indapamide exists in the form of a non-stoichiometric hydrate. The water molecules are only weakly and reversibly bound into the crystal structure. The major framework of the crystal structure, built of indapamide molecules, remains practically unchanged upon dehydration and/or hydration processes. In order to prove this hypothesis and understand the hydration-dehydration behavior, the as yet unknown crystal structure of indapamide needed to be determined. Since it was not possible to grow any adequate single crystals, we decided to solve the structure from laboratory X-ray powder diffraction data. The solved structure confirmed the hypothesis of weakly bound water in the voids between the indapamide molecules and also served as a basis to evaluate and explain the relative humidity dependence of the unit cell parameters of indapamide. PMID- 17283657 TI - Visualization and analysis of the release mechanism of shellac coated ascorbic acid pellets. AB - Shellac coated sustained release ascorbic acid containing pellets were investigated using scanning electron microscopy in order to visualize the release mechanism and to establish a correlation to dissolution data. Scanning electron micrograph pictures revealed different drug release profiles of individual pellets. Single pellet dissolution measurements demonstrated that the release profile of the encapsulated dosage form, containing approximately 400 pellets per capsule, is a combination of different release profiles of all individual pellets. The release of ascorbic acid occurred only in some small spots on the surface area of the pellets and could be visualized by the reduction of silver ions from an aqueous silver nitrate solution. These spots could be identified as defects in the shellac sustained release film using scanning electron microscopy. In further trials, the dissolution rate of an individual pellet could be related to the number and dimension of holes in its membrane. In conclusion, the release is characterized by surface defects and scanning electron microscopy studies are a useful tool to get new information for a better understanding of the drug release. PMID- 17283658 TI - Characterization of latex-antineoplastic drug complexes by differential scanning calorimetry and microphotography. AB - Choline kinase inhibitors have recently been identified as potentially useful antitumoral agents. Here we determine the best conditions for obtaining drug polymer complexes with 5-fluorouracil (5-FU), and JCR791B, a new drug representing a significant advance in the development of new molecules to inhibit tumour proliferation. As polymers we used the cellulose derivatives Aquacoat and Aquateric. The variables in the adsorption process measured were time to adsorbent-adsorbate equilibrium, pH and concentration. The drug-polymer complexes were characterized by differential scanning calorimetry and microphotography. Our results show that adsorption of 5-FU and JCR was similar with both polymers although slightly greater with Aquacoat. The chemical structure of the drug and its solubility in water and oil are fundamental characteristics that determine the performance of polymers as drug carriers able to provide controlled release. PMID- 17283659 TI - Stability of insulin under iontophoretic conditions. AB - The present study focuses on the physical and chemical stability of insulin under iontophoretic conditions using HPLC, SDS-PAGE, RIA and biological assay. Influence of pH, concentration of insulin, current strength and duration of current application on the stability of insulin was studied. Anodal iontophoresis at pH 7.4 caused more than 80% degradation of insulin, while the degradation was minimal at pH 3.6. The degradation was not influenced by insulin concentration, but increase in current strength above 0.75 mA/cm2 or application of current for 12 h (at 0.5 mA/cm2) led to 80 and 20% degradation respectively. All the samples showed biological activity comparable to intact insulin. PMID- 17283660 TI - Photoproducts and proposed degradation pathway in the riboflavin-sensitised photooxidation of isoproterenol. AB - Products of the aerobic visible-light-promoted riboflavin-sensitised photooxidation of the sympathomimetic drug isoproterenol were identified by means of HPLC and spectrophotometric techniques. The oxidative process, mediated by superoxide radical anion, generates N-isopropylaminochrome as a main photoproduct with a quantum yield of 0.15. In parallel, the photodecomposition of riboflavin is prevented in the presence of isoproterenol. A reaction scheme for the photooxidation pathway of isoproterenol is proposed in analogy to former reports for related compounds. PMID- 17283661 TI - A novel controlled porosity osmotic pump system for sodium ferulate. AB - A controlled porosity osmotic pump (CPOP) delivery system for sodium ferulate was prepared with cellulose acetate (CA) as semipermeable membrane, polyethyleneglycol 400 (PEG 400) as channeling agent and dibutylphthalate (DBP) as plasticizer and release controller. Effects of coating levels, PEG and DBP content and amount of sodium chloride on in vitro release were studied. Coating formulations were optimized by a L9 (34) orthogonal array design (OAD) with three factors at three levels using statistical analysis. Controlled porosity osmotic pump tablets of sodium ferulate made with the optimal formulation were found to have good in vitro and in vivo release characteristics. PMID- 17283662 TI - Cytotoxicity of a newly synthesized nitroxide derivative of 4-ferrocenecarboxyl 2,2,6,6-tetramethylpiperidine-1-oxyl in high metastatic lung tumor cells. AB - Low molecular weight nitroxides are widely used as electron paramagnetic resonance (EPR)-detectable spin labels in the biological and pathological areas. A novel nitroxide derivative, 4-ferrocenecarboxyl-2,2,6,6-tetramethyl piperidine 1-oxyl (FC-TEMPO), was synthesized for evaluating the effects of spin label compounds on tumor cells and firstly its biological effects on tumor and normal cells were evaluated. The cytotoxicity of FC-TEMPO in the high metastatic lung carcinoma cells (95-D) showed that it markedly inhibited the viability of cancer cells in a dose-dependent manner, while it was less toxic to a normal human cell line. Further studies found that FC-TEMPO suppressed the growth of tumor cells by induced apoptosis through activating caspase-3 but not caspase-8 which was proved by caspase inhibitors, and the cell cycle arrest at G1 phase. Moreover, the concomitant increase of superoxide dismutase (SOD) and catalase (CAT) activity was observed. Taken together, these results might provide a base for further anticancer investigations of nitroxides and their potential pharmacological applications. PMID- 17283663 TI - Phenolics from extracts of Brahea armata with inhibitory effect against 5alpha reductase type-II. AB - Fractions of the aqueous alcohol extracts of the rind and kernel of Brahea aramata fruits have been investigated for their activity against 5alpha-reductase type II, which is expressed predominantly in the prostate. This isozyme represents a major target for drugs against benign prostate hyperplasia (BPH) and prostate cancer. Also, a structural analysis of the phytophenolics, present in both aqueous alcohol extracts as the major constituents, has led to the isolation of five phenolics, including the new natural product, 4',6'-dimethoxy beta,4,2' trihydroxy chalcone from the rind extract and three phenolics, including the new natural product, 1-p-hydroxybenzoyl glycerol from the kernel extract. All structures were confirmed by ESI-MS and NMR analysis. PMID- 17283664 TI - A new limonoid from the fruits of Evodia rutaecarpa (Juss.) Benth. AB - Four limonoids have been isolated from the unripe fruits of Evodia rutaecarpa (Juss.) Benth., one of which is a new compound (1), identified as 23-oxo-21 hydroxy-21,23-dihydroevodol (named evodirutaenin), the known compounds were identified as evodol (2), limonin (3) and shihulimonin A (4), on the basis of the analysis of 1H NMR, 13C NMR, HSQC, HMBC, IR and MS spectral data. Shihulimonin A of known structure was also isolated from the unripe fruits of Evodia rutaecarpa for the first time. PMID- 17283665 TI - Janthinolide A-B, two new 2,5-piperazinedione derivatives from the endophytic Penicillium janthinellum isolated from the soft coral Dendronephthya sp. AB - Two new 2,5-piperazinedione derivatives, janthinolide A and B (1-2), along with deoxymycelianamide, griseofulvin and dechlorogriseofulvin were isolated from the fermentation broths of the endophytic fungus Penicillium janthinellum isolated from a soft coral, Dendronephthya sp. Their structures were established by extensive spectroscopic data analysis. PMID- 17283666 TI - Sublimation of antimycotic agents as proved by various analytical methods. AB - Qualitative and quantitative results demonstrate that the pure substances amorolfine base, amorolfine hydrochloride, two selected morpholine derivatives and terbinafine hydrochloride are clearly able to sublimate. As amorolfine hydrochloride is also capable to sublimate from galencial forms laquer and cream in this experimental setup, a clinical relevance of sublimation phenomenon at least for topical treatment of onychomycosis has to be considered. This phenomenon could be one reason for advantageous clinical and mycological cure rates of amorolfine nail laquer to comparable topical products reported in the literature. PMID- 17283667 TI - Properties of colour reference solutions of the European Pharmacopoea in CIE L*a*b* colour space. AB - The coordinates of CIE L*a*b* uniform colour space have been acquired from the transmitance spectra of colour reference solutions of European Pharmacopoeia (Ph.Eur.). Calculation of colour differences of these solutions from purified water deltaE* gave their values in the range between 0.7 (B9 solution) to 36 (Y1 solution) CIE units. Excluding red colour reference soulutions, deltaE* values did not depend on concentrations of colour compounds linearly. Small deltaE* values founded by the brown and brownish-yellow colour reference solutions of the lowest concentrations can possibly cause some problems of visual examination of the degree of coloration of liquids according to Ph.Eur. PMID- 17283668 TI - Efficiency of stabilization of low level of coloration of Castellani's paint without fuchsine with disodium edetate. AB - Addition of 0.03% of disodium edetate dihydrate (DED) was determined by observation of colour differences deltaE* in the CIELAB system to give more effective stabilisation of a low level of coloration of Castellani's paint without fuchsine than did 0.02% DED. Increase of the DED addition to 0.04% did not lead to further retardation of the increase in coloration of the preparation. PMID- 17283669 TI - Effect of beta-(1,3)-glucan on rheological properties and stability of topical formulations. AB - The paper deals with an effect of insoluble fungal beta-(1,3)-glucan on rheological properties of topical preparations. Two types of hydrogels (based on carbomer and polyacrylamide) and two types of hydrocreams (based on polysorbate 80/Span 80 and Brij 721TM/Brij 72) were prepared and investigated. The rheological properties of all these preparations were compared with the properties of placebos and they were measured after preparation and after 5 months of storage under different conditions: at 20 degrees C and 35 degrees C and after a triplicate freeze-thaw cycling process (-20 degrees C/+20 degrees C). In general it can be stated that with the exception of polyacrylamide hydrogel the beta-(1,3)-glucan presence increased the apparent viscosity of assessed preparations by approximately 10-20%. In the case of hydrocreams it was observed that the triplicate freeze-thaw cycling process increased the apparent viscosity of beta-(1,3)-glucan preparations by about 20-30%. PMID- 17283671 TI - So, who's your daddy? PMID- 17283670 TI - Bird flu takes flight. PMID- 17283672 TI - Busy is o.k. for kids. PMID- 17283673 TI - The new map of the brain. PMID- 17283674 TI - The mystery of consciousness. PMID- 17283675 TI - How the brain rewires itself. PMID- 17283676 TI - 6 lessons for handling stress. PMID- 17283677 TI - Five paths to understanding. PMID- 17283679 TI - What the mouse brain tells us. PMID- 17283678 TI - Time travel in the brain. PMID- 17283680 TI - What do babies know. PMID- 17283681 TI - Who should read your mind? PMID- 17283682 TI - How to change a personality. PMID- 17283683 TI - The flavor of memories. PMID- 17283684 TI - The gift of mimicry. PMID- 17283685 TI - Marketing to your mind. PMID- 17283686 TI - How we make life-and-death decisions. PMID- 17283687 TI - The power of hope. PMID- 17283688 TI - Tricks of the eye and limits of the brain. PMID- 17283692 TI - Educating parents through the use of digital radiography. PMID- 17283691 TI - A modified technique for direct Class II posterior composite restorations. PMID- 17283689 TI - Temporary endodontic restorations of previously restored teeth. PMID- 17283693 TI - Implant replacement of the maxillary central incisor: clinical and laboratory technique. PMID- 17283690 TI - Computer-guided immediate provisionalization of anterior multiple adjacent implants: surgical and prosthodontic rationale. AB - Immediate implant restoration has gained popularity in recent years due in part to technological advancements that use computed tomographic images to simulate the actual clinical situation. This computer-assisted simulation enables clinicians to develop a comprehensive treatment plan that can be precisely executed in a timely manner. In the aesthetic zone, however, a successful outcome requires more than merely accurate implant placement. This article discusses the significance of site development for aesthetic implant restoration and describes a computer-guided immediate pro visionalization procedure and its surgical and prosthodontic rationale PMID- 17283694 TI - The impression process: part II--application. PMID- 17283695 TI - A polychromatic composite layering approach for solving a complex Class IV/direct veneer-diastema combination: part I. AB - Direct resin bonding represents a conservative means of providing aesthetic restoration of the anterior dentition. Such techniques enable chairside control of colors, morphology, and ultimately, aesthetic results. For optimal integration, the clinician must thoroughly understand the capabilities of resin materials and their behavior when layered in direct resin buildups. This article demonstrates an advanced clinical technique for enhancing the appearance of the anterior dentition as achieved via tooth whitening and a combination of a Class IV restoration and a direct resin veneer PMID- 17283697 TI - Localized discoloration of central incisors: a case report. PMID- 17283696 TI - A practical and predictable clinical technique to pick up stud attachments for implant-retained overdentures. PMID- 17283698 TI - Treatment of edentulous and partially edentulous patients with CAD/CAM frameworks: a pilot case study. AB - Computer-assisted design/computer-assisted manufacturing (CAD/CAM) has been used successfully in commercial industry for several decades and is only now becoming more common for use within the clinical setting. This presentation will outline how CAD/CAM frameworks present numerous advantages over conventional castings when used to treat edentulous and partially edentulous patients in such areas as strength, biocompatibility, and precision machining. Recent advancements in CAD/CAM technology have decreased the costs associated with the fabrication of implant- and tooth-borne frameworks. PMID- 17283699 TI - Current status of methacrylate-based sealers and obturation techniques. PMID- 17283701 TI - Update on insulin pump therapy. PMID- 17283700 TI - New focus on nutrition in schools combined with oral health education can work toward combating childhood dental illness all year. PMID- 17283702 TI - Head lice: what seems to change, and what seems to stay the same. PMID- 17283703 TI - Caring for the student after spinal cord injury. PMID- 17283704 TI - Identifying food allergic children in schools: practical advice for school nurses. PMID- 17283705 TI - Bipolar disorder: an evolving understanding of the diagnosis. PMID- 17283706 TI - Helping hands: collaborating for coordinated school health programs. PMID- 17283707 TI - [Prostatic cancer. New diagnostic techniques]. PMID- 17283708 TI - [Prostate cancer. New diagnostic techniques. Current status of prostate biopsy]. AB - OBJECTIVES: Ultrasound guided prostate biopsy is the only method to obtain the confirmation diagnosis of prostate cancer. Since its introduction at the end of the '80s multiple modifications of the technique have been implemented to improve cancer detection rates and to diminish the rate of false negative results, with maximum patient comfort and less complications. METHODS: Bibliographic review and critical analysis of the literature on prostate biopsy. RESULTS/CONCLUSIONS: Published studies suggest extensive biopsy schemes increase detection rates in comparison to sextant biopsies, both first and successive biopsies, being necessary to sample the most lateral areas of the gland and the dorsal apex where the diagnostic yield is greater. The indications for repeated biopsies after a negative one include high grade PIN and/or Atypical Small Acinar Proliferation (ASAP), persistent PSA elevation and/or total PSA doubling time increase. There is no consensus about the time for repeating biopsies, although it seems that cancer detection rates descend after the third biopsy. The introduction of periprostatic anesthetic blockage techniques has enabled pain control, mainly in more extensive biopsies. PMID- 17283709 TI - [The diagnosis of prostate cancer by endorectal MR spectroscopy]. AB - OBJECTIVES: The endorectal MR spectroscopic imaging (MRS) is a new imaging technique that allows a more accurate and reliable evaluation for the localization and staging of prostate cancer(PCa) than the sole morphological study offered by endorectal MR alone. The combination of endorectal MRI and MRS allows a simultaneous morphologic and metabolic study that improves the detection of PCa. Moreover, the technical improvements recently introduced in the spectroscopic study of the prostate have led to an increase of reliability in the detection of PCa. METHODS AND RESULTS: We present in this article the advantages this technique offers in the detection of PCa in patients at high risk, as well as in patients with progressive PSA rising and previous negative biopsies. It also seems to be useful in the study of biochemical recurrences of PSA in previously treated patients, and for the study of the central gland. We comment, as well, the chance to use this tool in the staging of PCa. Our group is actually working with MRS in the detection of PCa, in collaboration with AATRM (Agency of Evaluation of medical technology for medical research) and we present some recent results in the use of this technique. CONCLUSIONS: MRS is a non-invasive method that allows the detection of PCa in the peripheral gland with a greater reliability than endorectal MRI alone, in selectyed patients. It is also a good technique for the study of the central gland, in which the detection of PCa is difficult by morphological methods. So, RMS allows the evaluation of metabolic disorders in the whole prostatic gland and improves the overall accuracy in the detection of PCa, either in the central or peripheral gland. PMID- 17283710 TI - [Advances in the ultrasound diagnosis of prostate cancer]. AB - OBJECTIVES: Ultrasound guided biopsies are the mainstay in the diagnosis of prostate cancer. With the aim of improving diagnostic performances different protocols of prostate biopsy have been designed. The addition of vascular contrasts to the ultrasound allows for identification of hypervascular regions more likely to be cancer. The new ultrasound modalities enhance contrast signal and specifically differentiate its signal from the tissue reflections. METHOD: A non structured review of the literature was conducted on the utility of the different ultrasound modalities and types in targeting the biopsies of the prostate. RESULTS: There are four types of ultrasound guided biopsies of the prostate: ultrasound guided biopsy of hypoechoic nodes, systematic biopsy protocols, Doppler guided biopsy and Contrast Enhanced Doppler guided biopsy. In spite of the broad literature only few series possess a methodologically correct design related to the use of reference standards. The diagnostic performance of each one of the different types of biopsy varies widely. Sensitivity and specificity of ultrasound guided biopsy of hypoechoic nodes depends on the type of population included in the study but in general its positive predictive value is low. The protocols of systematic biopsy increase the sensitivity of the prostate biopsy but still specificity is low. The Doppler techniques offer a marginal benefit. Contrast Enhanced Doppler guided biopsies series have reported only a slightly increase in sensitivity and a significant improvement of the odds risk for diagnostic of prostate cancer. New arising ultrasound modalities present with promising preliminary results. CONCLUSIONS: Ultrasound guided biopsy have an acceptable sensitivity in the diagnosis of prostate cancer, however specificity is overall low. Among the different ultrasound techniques only Contrast Enhanced Ultrasound improves significantly the diagnostic risk of the biopsy although the sensitivity remains quite stable. New specific contrast ultrasound techniques are currently under investigation. PMID- 17283711 TI - [Current value of seminal vesicle biopsy in patients with prostate cancer and influence of radical prostatectomy in patients with seminal vesicle invasion]. AB - OBJECTIVES: To evaluate if radical prostatectomy may positively influence cancer specific survival (CSS), hormone-resistance-free time, metastasis-free time, and quality of life(QoL) of patients with prostate adenocarcinoma and seminal vesicle invasion, and also to update our thoughts about seminal vesicle biopsy. METHODS: 114 patients were included. Forty-six cases were diagnosed of seminal vesicle invasion after radical prostatectomy; 68 cases were diagnosed of seminal vesicle invasion after biopsy, not undergoing then surgery. Cancer specific survival, time to hormone resistance from the start of hormonal treatment, metastasis free time and QoL, measured as need for hospital care, were compared between groups. Median follow-up time was 52.6 mos. RESULTS: There were not statistically significant differences between groups in CSS, time to hormone resistance, metastasis free time and QoL. Three and five-year cancer specific survival were 100% and 80.77% for the radical prostatectomy group and 74.4% and 56.2% for the biopsy group. Primary grade and Gleason Score were independent predictors for CSS in the Cox regression test; clinical stage was independent predictor for time to hormone resistance. CONCLUSIONS: Radical prostatectomy as monotherapy does not show a statistically significant influence on followup time, CSS, time to hormone resistance, metastasis free time or QoL in patients with prostate cancer and seminal vesicle invasion associated with other bad prognostic factors (unfavourable Gleason and PSA). The value of seminal vesicle biopsy remains for the study of new multimodal treatments, such as chemotherapy + surgery, and it is to be defined in the planning of radio and cryosurgery. PMID- 17283713 TI - [Current role of MRI for the local staging of prostate cancer]. AB - The management of prostate cancer represents a real clinical problem for its unknown natural history, and unpredictable outcome and prognosis. The stage is the most important prognostic variable of any tumor. The use of nomograms, such as Partin's tables, supplies important information for the evaluation of the local stage. Nevertheless, these methods have low reliability because they do not use anatomical information of the gland. The development of MRI techniques incorporating high-resolution anatomical evaluation of the prostate in conjunction with metabolic information (MRI spectroscopy) offer the imaging technique of choice for the staging of prostate cancer in selected patients candidates to curative surgery. Prostate MRI offers the most reliable evaluation of local and regional staging. Anyway, many studies have described a wide variability in the reliability of prostate cancer staging by MRI, indicating that MRI is not a perfect imaging test because it cannot detect microscopic involvement. The objective of this article is to evaluate the current role of prostatic MRI for prostate cancer staging, evaluating its advantages, limitations and future expectations. PMID- 17283712 TI - [Current validity of nomograms for prostate cancer staging]. AB - OBJECTIVE: [corrected] This paper presents a review of the concept of "nomogram" applied to prostate cancer, and specifically as a staging tool. METHODS/RESULTS: We describe the essential parameters for the evaluation of such type of predictive models: Calibration, discrimination and clinical usefulness. Such requisites are analyzed using a real clinical case in our clinical setting, comparing the "Partin's tables" and the "Miguel Servet University Hospital's nomogram". We demonstrate its correct calibration, discrimination and clinical usefulness after previous selection of proper cut points. CONCLUSION: The application of the predictive model to our clinical practice has achieved a clinical understaging of 17.3% after radical prostatectomy. PMID- 17283714 TI - [The diagnosis of prostate cancer dissemination]. AB - Prostate cancer preferentially metastasizes to regional lymph nodes and bone. The incidence of dissemination has been reduced over the last years mainly due to the compost use of PSA. For this reason, the indication of complementary diagnostic tests has evolved with the aim of improving the diagnostic yield. Some of these techniques are currently under evaluation and may contribute in the close future to change the study of dissemination in the clinical practice. CT scan or MRI are the standard imaging studies for lymph node dissemination, whereas bone scan continues to be the routine test for bone dissemination. PMID- 17283716 TI - [Bone mineral density evaluation: a new tool for the urologist]. AB - OBJECTIVES: To familiarize the urologist with the various diagnostic tests currently available for bone mineral density measurement, as well as to perform an update on bone mineral densitometry. METHODS: We review the currently available methods for the evaluation of bone mineral density, with special focus on dual energy X-ray ab-sorptiometry (DXA), considered the standard technique for the diagnosis of osteoporosis. We also review the role of peripheral densitometry and the use of ultrasounds for the evaluation of bone mass status. RESULTS: We may consider lumbar vertebrae and hip DXA the standard technique for the evaluation of bone mass. Peripheral devices and ultrasounds will probably have a very important role in the future. The lack of large prospective evaluation studies imply that its use is not being advised in daily clinical practice for diagnosis and follow-up of osteoporosis. CONCLUSIONS: We, as urologists, should become aware of the importance of bone health of our patients, especially those with prostate cancer, specifically for those receiving androgen deprivation therapies. To know some features of osteoporosis and how to diagnose and follow it may be very useful to diminish the impact this disease represents for our patient's morbidity and mortality. PMID- 17283715 TI - [Current value of positron emission tomography for prostate cancer follow-up]. AB - Positron emission tomography (PET) is a non-invasive nuclear medicine technology which uses radiotracers and cameras slightly different from the ones used in other nuclear medicine tests. Most current indications are for oncological diseases; in nephrology-urology its use has been reduced because of the characteristics of the most commonly used radiotracer, 18F-fluor deoxiglucose (18F-FDG, a glucose analogue), which is excreted by the kidney, limiting the interpretation of the study in urologic malignancies. Currently, 18F-choline is a promising radiotracer for both staging and restaging, especially if hybrid PET/CT scan devices are used. New radiotracers will be needed in the evolution of PET to obtain information about more specific aspects of prostate carcinoma that will modify therapy and follow-up. PMID- 17283718 TI - [Diagnostic methodology for the biochemical recurrence of prostate cancer after radiotherapy]. AB - OBJECTIVES: Due to the permanence of the prostate, PSA does not descend to undetectable levels after radical radiotherapy the way it happens after radical prostatectomy. PSA as response parameter after radiotherapy or for the characterization of biochemical recurrence is very sensitive but not much specific. The positive predictive value for local or systemic clinical recurrence is low, so that the use of PSA alone for the indication of rescue therapies is open to debate. There are different definitions of biochemical recurrence after radiotherapy. To date, the most standardized definition was that of the American Society for Therapeutic Radiology and Oncology (ASTRO) in 1996, but it was exclusive for patients treated with external beam radiotherapy as monotherapy. It was very sensitive to the follow-up time, but it was based on retrospective data, and its correlation with clinical progression was suboptimal. With the aim of improving the definition of biochemical failure ASTRO reunited a new expert commission in 2005 that gave a new definition of biochemical failure more specific for clinical events and valid in the context of short-term androgen deprivation or brachytherapy. The final recommendations were to consider biochemical recurrence a PSA increase of 2 ng/ml or greater over the nadir, or patients that have received rescue therapies. Prostate biopsy after radiotherapy is employed in patients with suspicion of exclusively local recurrence to direct them to rescue therapies. The criteria for the diagnosis of post-therapy carcinoma must be homogenized before establishing this test as a routine in the evaluation of treatment response. Standard imaging techniques for the localization of clinical recurrences (99-technetium bone scan, CT scan and MRI) are not much sensitive and it is predictable that other diagnostic tests which have a metabolic character (such as PET with various tracers, MR spectroscopy) will be used for the study of biochemical recurrence after radiotherapy in the near future. PMID- 17283717 TI - [Diagnostic methodology for the biochemical recurrence of prostate cancer after radical prostatectomy]. AB - Prostate cancer is one of the main health problems of the male population. Radical prostatectomy has demonstrated to have an excellent long-term cure rate. Nevertheless, globally, a 25% of the operated patients will suffer a PSA increase over 15 years of follow-up. Generally, the PSA value associated with a higher risk of clinical progression, that may be established as the cut point for biochemical recurrence is 0.4 ng/ ml. Once biochemical recurrence is diagnosed, the most important clinical data is to determine if clinical recurrence is going to be local or systemic, because it will determine treatment. Main parameters helping to differentiate between one and another are: time interval to PSA increase, PSA velocity, PSA doubling time (PSA-DT), pathologic stage and specimen's Gleason's score. The possibilities of treatment of biochemical failure after radical prostatectomy are under debate. Nevertheless, it is currently considered that patients with biochemical recurrence without radiological evidence of distant metastases are ideal candidates for local treatment with radiotherapy. PMID- 17283720 TI - [Current role of PSA and other markers in the diagnosis of prostate cancer]. AB - OBJECTIVES: To evaluate the current role of PSA as a diagnostic method for prostate cancer, as well as to analyze possible new markers. METHODS: We perform a bibliographic review for PSA, and its molecular forms, as a marker to define the presence of prostate cancer. We review the factors related to PSA modifications, predictive models, or the current controversies about the usefulness of its cutpoint to define the risk of prostate cancer or the marker itself. We analyze possible new markers and the most interesting work lines in the development of new markers. We used MEDLINE for the bibliographic search. RESULTS: Available data confirm that PSA has a high sensitivity; although specificity is low, mainly in the < 10 ng/ml range, it may be increased with the use of various molecular isoforms, ratios or predictive models. Nevertheless, it is true that despite such studies it is difficult to increase specificity, so biopsies are reduced. Currently we have new markers, some of them already marketed, others in development, which seem to improve the specificity of PSA (isoforms, use of molecular biology). CONCLUSIONS: PSA is still the standard marker for the diagnosis of prostate cancer. It is important to improve the specificity; therefore we need new predictive models or new isoforms that help us to do a better selection of candidates for biopsy. There are various promising research lines with new markers, but there is not ideal substitute for PSA yet. PMID- 17283719 TI - [Diagnostic methodology for the biochemical recurrence of prostate cancer after brachytherapy]. AB - Currently prostate cancer is the most frequent extracutaneous neoplasia in males in the USA, and second after lung cancer in our country. Over the last years the profile of prostate cancers diagnosed has changed due to the wide diffusion of PSA determination. Currently, almost 47% of prostate cancers are low risk at diagnosis. In this situation, the minimally invasive therapies such as brachytherapy have a growing acceptance in our environment. We analyze the special PSA kinetics after brachytherapy, and the difficulty entailed by the diagnosis of biochemical recurrence after brachytherapy, performing a bibliographic review of the available scientific evidence. PMID- 17283721 TI - [PSA doubling time as a new diagnostic and prognostic method for prostate cancer]. AB - OBJECTIVES: To review the value of PSA kinetics in the diagnosis and prognosis of prostate cancer. METHODS: Review of the literature through a Medline search. CONCLUSIONS: A pre-tretament PSAV value >2ng/ ml/yr is a risk factor for increased mortality from prostate cancer after surgery or radiation therapy. A PSADT<3ms is indicative of reduced survival after treatment. For patients with PSA recurrence after surgery a PSADT> 10 is more likely associated with local recurrence. PMID- 17283723 TI - Quantification of Mannheimia haemolytica leukotoxin by indirect ELISA. AB - An indirect enzyme-linked immunosorbent assay (ELISA) was developed for the quantification of extracellular leukotoxin (LKT) produced in chemostat culture of Mannheimia haemolytica in a serum-free culture medium. Leukotoxin purified with preparative SDS-PAGE was used for the production of chicken polyclonal antibodies (PAb) that served as the primary detecting antibody. Excising the LKT protein from an analytical SDS-PAGE gel proved an efficient technique for the purification of the toxin. Consequently, the 102 kDa LKT polypeptide purified in this manner served as reference toxin and the resulting calibration curve was modelled using a four parameter logistic fit to relate absorbance to LKT protein concentration. The lower detection limit corresponded to an LKT concentration of 14.5 ng ml(-1). The presence of SDS, serum albumin and the coating pH had a distinct effect on the absorbance values of the indirect ELISA. PMID- 17283724 TI - In vitro cultivation of a south African isolate of an Anaplasma sp. in tick cell cultures. AB - This paper describes the first successful in vitro cultivation of a South African isolate of an Anaplasma sp., initially thought to be Anaplasma marginale, in the continuous tick cell line IDE8. Blood from a bovine naturally infected with A. marginale kept on the farm Kaalplaas (28 degrees 08' E, 25 degrees 38' S) was collected, frozen, thawed and used as inoculum on confluent IDE8 cell cultures. Twenty days after culture initiation small intracellular colonies were detected in a Cytospin smear prepared from culture supernatant. Cultures were passaged on Day 34. Attempts to infect IRE/CTVM18 cell cultures with the Kaalplaas isolate derived from IDE8 cultures failed, whereas a reference stock of A. marginale from Israel infected IRE/CTVM18 tick cell cultures. Attempts to infect various mammalian cell lines (BA 886, SBE 189, Vero, L 929, MDBK) and bovine erythrocytes, kept under various atmospheric conditions, with tick cell-derived Anaplasma sp. or the Israeli strain of A. marginale failed. Molecular characterization revealed that the blood inoculum used to initiate the culture contained both A. marginale and Anaplasma sp. (Omatienne) whereas the organisms from established cultures were only Anaplasma sp. (Omatjenne). PMID- 17283725 TI - First record of Cylicospirura (Cylicospirura) felineus (Chandler, 1925) Sandground, 1933 (Nematoda: Spirocercidae) from a domestic cat in South Africa. AB - Cylicospirura (Cylicospirura) felineus (Chandler, 1925) Sandground, 1933 is reported from a cat in South Africa for the first time. The nematode was present in a gastric parasitic nodule in a male domestic cat, and three males were recovered as well as the anterior parts of three and the posterior parts of two gravid females. The heads of two specimens of undetermined sex were also found. Part of the removed parasitic nodule was processed for histopathological examination. The parasitic nodule was located in the submucosa and slightly expanded into the muscular layer. In its centre were small necrotic areas containing debris of inflammatory cells, adult nematodes and numerous bacterial colonies. Neutrophils, eosinophils, plasma cells and lymphocytes, as well as fibroblasts, were the predominant cell types. The serosal surface of the stomach remained unaffected. Some comparative morphological as well as ecological data concerning Cylicospirura (Cylicospirura) Vevers, 1922 in other feline hosts, mainly from Australia, India and North America, are included. PMID- 17283722 TI - [Late pathology advances in the diagnosis and prognosis of prostate cancer]. AB - This review article presents the late advances in the pathologic diagnosis of prostate cancer, new concepts and predictive factors, emphasizing the new biomolecular markers in prostate cancer. PMID- 17283726 TI - Elimination of toxicity and enhanced detection of lumpy skin disease virus on cell culture from experimentally infected bovine semen samples. AB - Lumpy skin disease virus (LSDV), a poxvirus of the genus Capripoxvirus, is shed in the semen of infected bulls. The screening of semen for infectious virus requires a sensitive diagnostic method. The isolation of the virus on cell cultures and/or the polymerase chain reaction (PCR) are sensitive diagnostic tests which may be used to screen semen for LSD viral DNA prior to artificial insemination. Although cell culture detects infectious virus and is a sensitive method, there are major difficulties in using this method due to the toxic effect of semen on the cells. The aim of this study was to find a method that decreases the toxic effect of semen and enhances the isolation of LSDV on cell culture. Semen samples from LSDV sero-negative bulls were collected and infected with a field isolate of LSDV, strain V248/93, with a titre of 6.5 log TCID50. The semen samples were treated with one of four different methods: centrifugation, serial dilution, filtration and chemical treatment with kaolin. The samples subjected to centrifugation, serial dilution and filtration were supplemented with gentamycin. Semen toxicity on cell cultures was eliminated when supernatants of semen samples centrifuged at 2000 rpm for 1, 3 and 5 min and serially diluted were used to inoculate confluent monolayer bovine dermis cells. The toxicity recorded when the pellet fractions of semen samples centrifuged for 5 min at 2000 rpm was comparable to results obtained from serially diluted samples supplemented with gentamycin. Filtration and kaolin treatment of semen samples did not remove the toxic effect. PMID- 17283727 TI - The socio-economic impact of important camel diseases as perceived by a pastoralist community in Kenya. AB - This paper presents the results of a study conducted in a pastoral community in Kenya using participatory appraisal approaches. The objective of the study was to assess the socio-economic impact of camel trypanosomosis (surra) according to the perceptions of the pastoralists. Four livestock grazing units were conveniently selected and in each of them, three groups of key informants comprising five to eight persons were selected for the participatory exercises. Five camel diseases were listed in order of importance according to their severity and frequency of occurrence including trypanosomosis, mange, non-specific diarrhoea, tick infestations and haemorrhagic septicaemia. The losses listed as incurred due to the five diseases were: losses in milk, meat, blood, fats and hides, dowry payments, and depreciation in sale of animals, losses due to infertility and abortions, and losses due to the cost of treatment. There was good agreement (P < 0.05) between the informant groups on the losses incurred as a result of the diseases for all the selected loss indicators. Surra and mange were given high median scores on all the indicators while non-specific diarrhoea, tick infestations, and haemorrhagic septicaemia received moderate median scores. Based on the study findings it is concluded that the camel plays a central role in the lives of Turkana pastoralists and that surra has a devastating social and economic impact. There is a need for veterinary and policy decision-makers to focus more attention on the control of surra in this arid and semi-arid area of Kenya. PMID- 17283728 TI - Comparative fluke burden and pathology in condemned and non-condemned cattle livers from selected abattoirs in Zambia. AB - After dissecting 70 condemned and 32 non-condemned cattle livers collected from Lusaka, Chisamba, Mongu and Senanga abattoirs and Turnpike slaughter slab, significantly higher numbers of liver flukes (Fasciola gigantica) (P < 0.001) were found in the condemned livers (mean +/- SD = 100.6 +/- 16.7) than in the non condemned livers (mean +/- SD = 0.7 +/- 0.5). Liver flukes found in 9.4% of the non-condemned livers suggest that abattoir records of liver inspection may underestimate F. gigantica infections. Average faecal fluke egg counts from animals with condemned livers (5 eggs per gram [EPG]) were significantly higher (P < 0.001) than in animals with non-condemned livers (0.8 EPG). No correlation was found between egg counts and number of flukes. Fibrosis and calcification were common in condemned livers, being severest in the vicinity of the bile ducts. Only two (6.3%) of the non-condemned livers showed pathological changes on the liver edges. The severe liver damage and high worm burden may explain low production levels experienced in cattle in Zambia maintained under traditional systems of management where worm control and good management programmes are rarely practiced. PMID- 17283729 TI - Mediorhynchus gallinarum (Acanthocephala: Gigantorhynchidae) in Helmeted guineafowls, Numida meleagris, in the Kruger National Park, South Africa. AB - Mediorhynchus gallinarum was recovered from the small intestines of 36 of 50 Helmeted guineafowls sampled from August 1988 to May 1989. The intensity of infection ranged from 1-141 worms per host, with a mean intensity of 23.2 (+/- 34) and a median intensity of 5. The Wilcoxon-Mann-Whitney test revealed no significant differences between the mean worm burdens of male and female birds at the 5% level (P > 0.05). Slightly more female than male acanthocephalans were collected. The majority (63.4%) of females had eggs with fully-developed embryos, 9% had immature eggs, 21.2% had no eggs and the egg status of 6.4% could not be determined. No seasonal pattern of intensity of infection emerged from the data, but worm burdens were markedly higher after good rains in February 1989. South Africa constitutes a new geographic record for M. gallinarum. PMID- 17283730 TI - An experimental intratonsilar infection model for bovine tuberculosis in African buffaloes, Syncerus caffer. AB - An infection model for Mycobacterium bovis in African buffaloes, Syncerus caffer, was developed, using the intratonsilar route of inoculation. Two groups of 11 buffaloes each, aged approximately 18 months, were infected with either 3.2 x 10(2) cfu (low dose) or 3 x 10(4) cfu (high dose) of M. bovis strain isolated from a buffalo. A control group of six buffaloes received saline via the same route. The infection status was monitored in vivo using the comparative intradermal tuberculin test, and in vitro by the modified interferon-gamma assay. All buffaloes were euthanazed 22 weeks post infection and lesion development was assessed by macroscopic examination, culture and histopathology. It was found that the high dose caused macroscopic lesions in nine out of 11 buffaloes. Mycobacterium bovis was isolated from all buffaloes in the high-dose group and from six out of 11 in the low-dose group. PMID- 17283731 TI - Ixodid ticks on dogs in the eastern region of the Eastern Cape Province, South Africa. AB - The objective of this study was to determine the species composition and geographic distribution of ixodid ticks infesting domestic dogs in the eastern region of the Eastern Cape Province. Seventy-two communal cattle dip-tanks within this region were randomly selected as survey localities and their geographic coordinates recorded. In addition to ticks that were collected from five cattle and five goats at each of the dip-tanks, ticks were also collected from five dogs whenever possible. No dogs were available at 19 dip-tanks and no ticks were collected from dogs at 13 dip-tanks, while ticks were collected from 132 of 200 dogs at 40 dip-tanks. Eight ixodid tick species were collected from these dogs, and Haemaphysalis leachi followed by Rhipicephalus appendiculatus and Rhipicephalus simus were present on dogs at the largest number of dip-tanks. Seven dogs were simultaneously infested with three tick species and one with four species. The geographic distributions of Amblyomma hebraeum, H. leachi, R. appendiculatus and R. simus recovered from the dogs lay within the ranges previously reported for these ticks. PMID- 17283732 TI - Helminth parasites of gemsbok (Oryx gazella) in the Klein Karoo. AB - The number and species of helminth parasites from three gemsbok (Oryx gazella) were recorded, and their faecal nematode egg counts and the level of pasture contamination determined. Six nematode genera were recovered and four species identified, of which Trichostrongylus rugatus was the most prevalent. Other nematode species recovered were Cooperia sp., Agriostomum sp., Haemonchus contortus, Nematodirus spathiger and Ostertagia ostertagi. None of the worms were present in all animals studied, and no new host associations were found. Cysticerci were recovered from the mesenteries of one gemsbok and a further two unidentifiable helminths were recovered from the abomasum and the kidney fat layer of another antelope. PMID- 17283733 TI - Eustrongylides sp. (Nematoda: Dioctophymatoidea) from the stomach of a Nile crocodile, Crocodylus niloticus Laurenti, 1768, in Botswana. AB - During a study conducted between 2003 and 2005 on the diet of Nile crocodiles in Botswana, two young adult nematodes, one male and one female, belonging to the genus Eustrongylides Jagerskiold, 1909 were recovered from the stomach contents of one of these animals. The caudal bursa of the male is present and the ejaculatory duct could be identified, but the spicule could not be seen. The vulva of the female has opened and the anus is situated on a terminal protruberance. Measurements and drawings of these specimens are provided, together with some data on the occurrence and life-cycles of members of the genus Eustrongylides in crocodilians world-wide and in African hosts in particular. Piscivorous birds are the usual final hosts of these nematodes. It is probable that the specimens described herein had developed in a paratenic fish host, and that the latter had been eaten by the crocodile. PMID- 17283734 TI - Protective netting, an additional method for the integrated control of livestock trypanosomosis in KwaZulu-Natal Province, South Africa. AB - Studies were conducted in KwaZulu-Natal, South Africa, to evaluate the effectiveness of netting in preventing Glossina austeni and Glossina brevipalpis from entering H-traps. Results indicated that a net of 1.5 m in height was effective in reducing catches of G. austeni by 59.6% and catches of G. brevipalpis by 80.9%. Increasing the net height to 2.5 m, reduced catches by 96.6% and 100% for G. brevipalpis and G. austeni, respectively. Nets of this height also reduced catches of horse flies by 55%. Although the potential use of protective netting has limitations in tsetse-infested areas of rural northern KwaZulu-Natal, it is a low-technology method that can be used as part of integrated disease management strategies. PMID- 17283735 TI - Cancer--treatment through the continuum. PMID- 17283737 TI - From integrative to multidimensional medicine. PMID- 17283738 TI - Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1. AB - PURPOSE: Some in the oncology community contend that patients undergoing chemotherapy and/or radiation therapy should not use food supplement antioxidants and other nutrients. Oncologists at an influential oncology institution contended that antioxidants interfere with radiation and some chemotherapies because those modalities kill by generating free radicals that are neutralized by antioxidants, and that folic acid interferes with methotrexate. This is despite the common use of amifostine and dexrazoxane, 2 prescription antioxidants, during chemotherapy and/or radiation therapy. DESIGN: To assess all evidence concerning antioxidant and other nutrients used concomitantly with chemotherapy and/or radiation therapy, the MEDLINE and CANCERLIT databases were searched from 1965 to November 2003 using the words vitamins, antioxidants, chemotherapy, and radiation therapy. Bibliographies of articles were searched. All studies reporting concomitant nutrient use with chemotherapy and/or radiation therapy (280 peer-reviewed articles including 62 in vitro and 218 in vivo) were indiscriminately included. RESULTS: Fifty human clinical randomized or observational trials have been conducted, involving 8,521 patients using beta-carotene; vitamins A, C, and E; selenium; cysteine; B vitamins; vitamin D3; vitamin K3; and glutathione as single agents or in combination. CONCLUSIONS: Since the 1970s, 280 peer-reviewed in vitro and in vivo studies, including 50 human studies involving 8,521 patients, 5,081 of whom were given nutrients, have consistently shown that non-prescription antioxidants and other nutrients do not interfere with therapeutic modalities for cancer. Furthermore, they enhance the killing of therapeutic modalities for cancer, decrease their side effects, and protect normal tissue. In 15 human studies, 3,738 patients who took non-prescription antioxidants and other nutrients actually had increased survival. PMID- 17283739 TI - A large-sample survey of first- and second-year medical student attitudes toward complementary and alternative medicine in the curriculum and in practice. AB - PURPOSE: To assess attitudes toward complementary and alternative medicine (CAM) and its place in the medical school curriculum and medical practice among preclinical students at Georgetown University School of Medicine (GUSOM), Washington, DC. METHOD: Two-hundred sixty-six first-year (n=111) and second-year (n=155) medical students rated their attitudes toward CAM and 15 CAM modalities in terms of personal use, inclusion in the curriculum, and use/utility in clinical practice. RESULTS: Nearly all (91%) students agreed that "CAM includes ideas and methods from which Western medicine could benefit"; more than 85% agreed that "knowledge about CAM is important to me as a student/future practicing health professional"; and more than 75% felt that CAM should be included in the curriculum. Among all students, the most frequently indicated level of desired training was "sufficient to advise patients about use," for 11 of the 15 modalities. The greatest level of training was wanted for acupuncture, chiropractic, herbal medicine, and nutritional supplements. The descriptions of CAM in future clinical practice that occurred most frequently were endorsement, referral, or provision of acupuncture, biofeedback, chiropractic, herbal medicine, massage, nutritional supplements, prayer, and meditation. CONCLUSIONS: Interest in and enthusiasm about CAM modalities was high in this sample; personal experience was much less prevalent. Students were in favor of CAM training in the curriculum to the extent that they could provide advice to patients; the largest proportions of the sample planned to endorse, refer patients for, or provide 8 of the 15 modalities surveyed in their future practice. PMID- 17283740 TI - Brief meditation training can improve perceived stress and negative mood. AB - OBJECTIVES: To test a brief, non-sectarian program of meditation training for effects on perceived stress and negative emotion, and to determine effects of practice frequency and test the moderating effects of neuroticism (emotional lability) on treatment outcome. DESIGN AND SETTING: The study used a single group, open-label, pre-test post-test design conducted in the setting of a university medical center. PARTICIPANTS: Healthy adults (N=200) interested in learning meditation for stress-reduction were enrolled. One hundred thirty-three (76% females) completed at least 1 follow-up visit and were included in data analyses. INTERVENTION: Participants learned a simple mantra-based meditation technique in 4, 1-hour small-group meetings, with instructions to practice for 15 20 minutes twice daily. Instruction was based on a psychophysiological model of meditation practice and its expected effects on stress. OUTCOME MEASURES: Baseline and monthly follow-up measures of Profile of Mood States; Perceived Stress Scale; State-Trait Anxiety Inventory (STAI); and Brief Symptom Inventory (BSI). Practice frequency was indexed by monthly retrospective ratings. Neuroticism was evaluated as a potential moderator of treatment effects. RESULTS: All 4 outcome measures improved significantly after instruction, with reductions from baseline that ranged from 14% (STAI) to 36% (BSI). More frequent practice was associated with better outcome. Higher baseline neuroticism scores were associated with greater improvement. CONCLUSIONS: Preliminary evidence suggests that even brief instruction in a simple meditation technique can improve negative mood and perceived stress in healthy adults, which could yield long-term health benefits. Frequency of practice does affect outcome. Those most likely to experience negative emotions may benefit the most from the intervention. PMID- 17283741 TI - The Gonzalez therapy and cancer: a collection of case reports. PMID- 17283742 TI - Integrative oncology: the last ten years--a personal retrospectve. AB - In the last decade, there has been dramatic changes in all areas of integrative patient care. None has been more dramatic than those in the field of cancer care, which has gone from alternative and complementary treatments delivered outside the conventional setting to the integration of many of these approaches into the care of the cancer patient. In many cases, these changes have been driven by patient demand and supported by private funding and out-of-pocket payments by patients themselves. Virtually all major medical centers have departments devoted to integrative patient care--whether true stand-alone centers or departments with a research interest in this area. This is particularly true of the major cancer centers, many of which-including Memorial Sloan Kettering Cancer Center, New York; M.D. Anderson Cancer Center, Houston, Tex; Johns Hopkins University, Baltimore, Md; Duke University, Durham, NC; and the Dana Farber Cancer Institute, Boston, Mass--have developed integrative cancer programs. In addition, programs such as the Cancer Treatment Centers of America have inpatient and outpatient programs with teams of practitioners, including medical oncologists, surgeons, and radiation therapists, as well as credentialed naturopathic doctors, nutritionists, mind-body specialists and other integrative practitioners. Despite the increased interest in developing integrative approaches to cancer, many medical oncologists remain skeptical about the value of these modalities. PMID- 17283743 TI - Nicholas J. Gonzalez, MD: seeking the truth in the fight against cancer. PMID- 17283745 TI - [Humanized yeasts]. PMID- 17283746 TI - [Antacids--an historical overview]. PMID- 17283744 TI - [A new in vitro model of HIV infections]. PMID- 17283747 TI - [Medicinal chemistry of histamine H2 receptor antagonists]. PMID- 17283748 TI - [Antacids--efficient and reasonably priced]. PMID- 17283750 TI - [Antacids and H2 antihistaminics for hyperacidity]. PMID- 17283749 TI - [H2 blockers and antacids in gastrointestinal diseases]. PMID- 17283751 TI - [Self medication with antacids and H2 antihistaminics]. PMID- 17283752 TI - Assessing patients for risk of colorectal cancer in primary care. PMID- 17283753 TI - Can peptic ulcer disease be prevented? PMID- 17283754 TI - FAQs: irritable bowel syndrome. PMID- 17283755 TI - Be vigilant for symptoms of bipolar disorder. PMID- 17283756 TI - Manage the patient with whiplash. PMID- 17283757 TI - Basal and squamous cell carcinoma. PMID- 17283758 TI - Structure your answers for the written paper. PMID- 17283760 TI - On the convergence of generalized simultaneous iterative reconstruction algorithms. AB - In this paper, we generalize the widely used simultaneous block iterative reconstruction algorithm and show that it converges, at a linear rate, to a weighted least-squares and weighted minimum-norm reconstruction. Our theoretical result provides a much simpler proof of the convergence properties obtained by Jiang and Wang and covers a much more general class of algorithms. The frequency domain iterative reconstruction algorithm is then introduced as a special application of our theory. PMID- 17283761 TI - Shape-from-shading using the heat equation. AB - This paper offers two new directions to shape-from-shading, namely the use of the heat equation to smooth the field of surface normals and the recovery of surface height using a low-dimensional embedding. Turning our attention to the first of these contributions, we pose the problem of surface normal recovery as that of solving the steady state heat equation subject to the hard constraint that Lambert's law is satisfied. We perform our analysis on a plane perpendicular to the light source direction, where the z component of the surface normal is equal to the normalized image brightness. The x - y or azimuthal component of the surface normal is found by computing the gradient of a scalar field that evolves with time subject to the heat equation. We solve the heat equation for the scalar potential and, hence, recover the azimuthal component of the surface normal from the average image brightness, making use of a simple finite difference method. The second contribution is to pose the problem of recovering the surface height function as that of embedding the field of surface normals on a manifold so as to preserve the pattern of surface height differences and the lattice footprint of the surface normals. We experiment with the resulting method on a variety of real world image data, where it produces qualitatively good reconstructed surfaces. PMID- 17283762 TI - Hypercomplex Fourier transforms of color images. AB - Fourier transforms are a fundamental tool in signal and image processing, yet, until recently, there was no definition of a Fourier transform applicable to color images in a holistic manner. In this paper, hypercomplex numbers, specifically quaternions, are used to define a Fourier transform applicable to color images. The properties of the transform are developed, and it is shown that the transform may be computed using two standard complex fast Fourier transforms. The resulting spectrum is explained in terms of familiar phase and modulus concepts, and a new concept of hypercomplex axis. A method for visualizing the spectrum using color graphics is also presented. Finally, a convolution operational formula in the spectral domain is discussed. PMID- 17283763 TI - Cheating prevention in visual cryptography. AB - Visual cryptography (VC) is a method of encrypting a secret image into shares such that stacking a sufficient number of shares reveals the secret image. Shares are usually presented in transparencies. Each participant holds a transparency. Most of the previous research work on VC focuses on improving two parameters: pixel expansion and contrast. In this paper, we studied the cheating problem in VC and extended VC. We considered the attacks of malicious adversaries who may deviate from the scheme in any way. We presented three cheating methods and applied them on attacking existent VC or extended VC schemes. We improved one cheat-preventing scheme. We proposed a generic method that converts a VCS to another VCS that has the property of cheating prevention. The overhead of the conversion is near optimal in both contrast degression and pixel expansion. PMID- 17283764 TI - Signal and image approximation using interval wavelet transform. AB - In signal approximation, classical wavelet synthesis are known to produce Gibbs like phenomenon around discontinuities when wavelet coefficients in the cone of influence of the discontinuities are quantized. By analyzing a function in a piecewise manner, filtering across discontinuities can be avoided. Using this principle, the interval wavelet transform can generate sparser representations in the vicinity of discontinuities than classical wavelet transforms. This work introduces two new constructions of interval wavelets and shows how they can be used for image compression and upscaling. PMID- 17283766 TI - Image coding with geometric wavelets. AB - This paper describes a new and efficient method for low bit-rate image coding which is based on recent development in the theory of multivariate nonlinear piecewise polynomial approximation. It combines a binary space partition scheme with geometric wavelet (GW) tree approximation so as to efficiently capture curve singularities and provide a sparse representation of the image. The GW method successfully competes with state-of-the-art wavelet methods such as the EZW, SPIHT, and EBCOT algorithms. We report a gain of about 0.4 dB over the SPIHT and EBCOT algorithms at the bit-rate 0.0625 bits-per-pixels (bpp). It also outperforms other recent methods that are based on "sparse geometric representation." For example, we report a gain of 0.27 dB over the Bandelets algorithm at 0.1 bpp. Although the algorithm is computationally intensive, its time complexity can be significantely reduced by collecting a "global" GW n-term approximation to the image from a collection of GW trees, each constructed separately over tiles of the image. PMID- 17283765 TI - Histogram of Gabor phase patterns (HGPP): a novel object representation approach for face recognition. AB - A novel object descriptor, histogram of Gabor phase pattern (HGPP), is proposed for robust face recognition. In HGPP, the quadrant-bit codes are first extracted from faces based on the Gabor transformation. Global Gabor phase pattern (GGPP) and local Gabor phase pattern (LGPP) are then proposed to encode the phase variations. GGPP captures the variations derived from the orientation changing of Gabor wavelet at a given scale (frequency), while LGPP encodes the local neighborhood variations by using a novel local XOR pattern (LXP) operator. They are both divided into the nonoverlapping rectangular regions, from which spatial histograms are extracted and concatenated into an extended histogram feature to represent the original image. Finally, the recognition is performed by using the nearest-neighbor classifier with histogram intersection as the similarity measurement. The features of HGPP lie in two aspects: 1) HGPP can describe the general face images robustly without the training procedure; 2) HGPP encodes the Gabor phase information, while most previous face recognition methods exploit the Gabor magnitude information. In addition, Fisher separation criterion is further used to improve the performance of HGPP by weighing the subregions of the image according to their discriminative powers. The proposed methods are successfully applied to face recognition, and the experiment results on the large-scale FERET and CAS-PEAL databases show that the proposed algorithms significantly outperform other well-known systems in terms of recognition rate. PMID- 17283767 TI - Heterogeneity-projection hard-decision color interpolation using spectral-spatial correlation. AB - This paper presents a novel heterogeneity-projection hard-decision (HPHD) color interpolation procedure for reproduction of Bayer mosaic images. The proposed algorithm aims to estimate the optimal interpolation direction and perform hard decision interpolation, in which each pixel only needs to be interpolated once. A new heterogeneity-projection scheme based on a novel spectral-spatial correlation concept is proposed to estimate the best interpolation direction directly from the original mosaic image. Using the proposed heterogeneity-projection scheme, a hard-decision rule can be decided before performing the interpolation. The advantage of this scheme is that it provides an efficient way for decision-based algorithms to generate improved results using fewer computations. Compared with three recently reported demosaicing techniques, Gunturk's, Lu's, and Li's methods, the proposed HPHD outperforms all of them in both PSNR values and S CIELAB deltaEab measures by utilizing 25 natural images from Kodak PhotoCD. PMID- 17283768 TI - A multilinear constraint on dichromatic planes for illumination estimation. AB - A new multilinear constraint on the color of the scene illuminant based on the dichromatic reflection model is proposed. The formulation avoids the problem, common to previous dichromatic methods, of having to first identify pixels corresponding to the same surface material. Once pixels from two or more materials have been identified, their corresponding dichromatic planes can be intersected to yield the illuminant color. However, it is not always easy to determine which pixels from an arbitrary region of an image belong to which dichromatic plane. The image region may cover an area of the scene encompassing several different materials and, hence, pixels from several different dichromatic planes. The new multilinear constraint accounts for this multiplicity of materials and provides a mechanism for choosing the most plausible illuminant from a finite set of candidate illuminants. The performance of this new method is tested on a database of real images. PMID- 17283770 TI - Lossless compression of color map images by context tree modeling. AB - Significant lossless compression results of color map images have been obtained by dividing the color maps into layers and by compressing the binary layers separately using an optimized context tree model that exploits interlayer dependencies. Even though the use of a binary alphabet simplifies the context tree construction and exploits spatial dependencies efficiently, it is expected that an equivalent or better result would be obtained by operating directly on the color image without layer separation. In this paper, we extend the previous context-tree-based method to operate on color values instead of binary layers. We first generate an n-ary context tree by constructing a complete tree up to a predefined depth, and then prune out nodes that do not provide compression improvements. Experiments show that the proposed method outperforms existing methods for a large set of different color map images. PMID- 17283771 TI - Feature-oriented multiple description wavelet-based image coding. AB - We address the problem of resilient image coding over error-prone networks where packet losses occur. Recent literature highlights the multiple description coding (MDC) as a promising approach to solve this problem. In this paper, we introduce a novel wavelet-based multiple description image coder, referred to as the feature-oriented MDC (FO-MDC). The proposed multiple description (MD) coder exploits the statistics of the wavelet coefficients and identifies the subsets of samples that are sensitive to packet loss. A joint optimization between tree pruning and quantizer selection in the rate-distortion sense is used in order to allocate more bits to these sensitive coefficients. When compared with the state of-the-art MD scalar quantization coder, the proposed FO-MDC yields a more efficient central-side distortion tradeoff control mechanism. Furthermore, it proves to be more robust for image transmission even with high packet loss ratios, which makes it suitable for protecting multimedia streams over packet erasure channels. PMID- 17283769 TI - Rate distortion analysis of motion side estimation in Wyner-Ziv video coding. AB - Wyner-Ziv video coding (WZVC) has gained considerable interests in the research community. In this paper, we present a model to examine the WZVC performance and compare it with conventional motion-compensated prediction (MCP) based video coding. Theoretical results show that although WZVC can achieve as much as 6-dB gain over conventional video coding without motion search, it still falls 6 dB or more behind current best MCP-based INTER-frame video coding. We further study the use of subpixel and multireference motion search methods to improve WZVC efficiency. The analytical results are confirmed by simulations and experiments. PMID- 17283772 TI - Demosaicing with directional filtering and a posteriori decision. AB - Most digital cameras use a color filter array to capture the colors of the scene. Downsampled versions of the red, green, and blue components are acquired, and an interpolation of the three colors is necessary to reconstruct a full representation of the image. This color interpolation is known as demosaicing. The most effective demosaicing techniques proposed in the literature are based on directional filtering and a posteriori decision. In this paper, we present a novel approach to this reconstruction method. A refining step is included to further improve the resulting reconstructed image. The proposed approach requires a limited computational cost and gives good performance even when compared to more demanding techniques. PMID- 17283773 TI - Estimation of multiple accelerated motions using chirp-Fourier transform and clustering. AB - Motion estimation in the spatiotemporal domain has been extensively studied and many methodologies have been proposed, which, however, cannot handle both time varying and multiple motions. Extending previously published ideas, we present an efficient method for estimating multiple, linearly time-varying motions. It is shown that the estimation of accelerated motions is equivalent to the parameter estimation of superpositioned chirp signals. From this viewpoint, one can exploit established signal processing tools such as the chirp-Fourier transform. It is shown that accelerated motion results in energy concentration along planes in the 4-D space: spatial frequencies-temporal frequency-chirp rate. Using fuzzy c planes clustering, we estimate the plane/motion parameters. The effectiveness of our method is verified on both synthetic as well as real sequences and its advantages are highlighted. PMID- 17283774 TI - Shape-based averaging. AB - A new method for averaging multidimensional images is presented, which is based on signed Euclidean distance maps computed for each of the pixel values. We refer to the algorithm as "shape-based averaging" (SBA) because of its similarity to Raya and Udupa's shape-based interpolation method. The new method does not introduce pixel intensities that were not present in the input data, which makes it suitable for averaging nonnumerical data such as label maps (segmentations). Using segmented human brain magnetic resonance images, SBA is compared to label voting for the purpose of averaging image segmentations in a multiclassifier fashion. SBA, on average, performed as well as label voting in terms of recognition rates of the averaged segmentations. SBA produced more regular and contiguous structures with less fragmentation than did label voting. SBA also was more robust for small numbers of atlases and for low atlas resolutions, in particular, when combined with shape-based interpolation. We conclude that SBA improves the contiguity and accuracy of averaged image segmentations. PMID- 17283775 TI - Random spray Retinex: a new Retinex implementation to investigate the local properties of the model. AB - In order to investigate the local filtering behavior of the Retinex model, we propose a new implementation in which paths are replaced by 2-D pixel sprays, hence the name "random spray Retinex." A peculiar feature of this implementation is the way its parameters can be controlled to perform spatial investigation. The parameters' tuning is accomplished by an unsupervised method based on quantitative measures. This procedure has been validated via user panel tests. Furthermore, the spray approach has faster performances than the path-wise one. Tests and results are presented and discussed. PMID- 17283776 TI - Facial expression recognition in image sequences using geometric deformation features and Support Vector Machines. AB - In this paper, two novel methods for facial expression recognition in facial image sequences are presented. The user has to manually place some of Candide grid nodes to face landmarks depicted at the first frame of the image sequence under examination. The grid-tracking and deformation system used, based on deformable models, tracks the grid in consecutive video frames over time, as the facial expression evolves, until the frame that corresponds to the greatest facial expression intensity. The geometrical displacement of certain selected Candide nodes, defined as the difference of the node coordinates between the first and the greatest facial expression intensity frame, is used as an input to a novel multiclass Support Vector Machine (SVM) system of classifiers that are used to recognize either the six basic facial expressions or a set of chosen Facial Action Units (FAUs). The results on the Cohn-Kanade database show a recognition accuracy of 99.7% for facial expression recognition using the proposed multiclass SVMs and 95.1% for facial expression recognition based on FAU detection. PMID- 17283777 TI - Expression-invariant representations of faces. AB - Addressed here is the problem of constructing and analyzing expression-invariant representations of human faces. We demonstrate and justify experimentally a simple geometric model that allows to describe facial expressions as isometric deformations of the facial surface. The main step in the construction of expression-invariant representation of a face involves embedding of the facial intrinsic geometric structure into some low-dimensional space. We study the influence of the embedding space geometry and dimensionality choice on the representation accuracy and argue that compared to its Euclidean counterpart, spherical embedding leads to notably smaller metric distortions. We experimentally support our claim showing that a smaller embedding error leads to better recognition. PMID- 17283778 TI - Design of tone-dependent color-error diffusion halftoning systems. AB - Grayscale error diffusion introduces nonlinear distortion (directional artifacts and false textures), linear distortion (sharpening), and additive noise. Tone dependent error diffusion (TDED) reduces these artifacts by controlling the diffusion of quantization errors based on the input graylevel. We present an extension of TDED to color. In color-error diffusion, which color to render becomes a major concern in addition to finding optimal dot patterns. We propose a visually meaningful scheme to train input-level (or tone-) dependent color-error filters. Our design approach employs a Neugebauer printer model and a color human visual system model that takes into account spatial considerations in color reproduction. The resulting halftones overcome several traditional error diffusion artifacts and achieve significantly greater accuracy in color rendition. PMID- 17283780 TI - Enhancement of low-contrast curvilinear features in imagery. AB - A new method is described for enhancing low-contrast curvilinear features in imagery that combines directional filtering with Fischler, Tenenbaum and Wolf's F* algorithm for computing minimum cost paths. The method exploits a phenomenon called "the stability of lines over angle." The idea is that when a directionally filtered image contains a line plus noise, minimum cost paths tend to be aligned in the direction of the line with random jumps between parallel paths. When the input image contains noise only, the direction of minimum cost paths resemble random walks with drift. As the direction of the filter changes, minimum cost paths that follow true features persist and are more stable over angle than those that follow noise. Adding them up in an accumulator array over angle produces a larger number of votes along signal paths than along noise paths. This provides a means for enhancing trajectories of low-contrast features. Several examples illustrate the enhancement of forest trails in USGS aerial imagery, linear features on Mars, and roads in synthetic aperture radar imagery. PMID- 17283779 TI - Multilinear discriminant analysis for face recognition. AB - There is a growing interest in subspace learning techniques for face recognition; however, the excessive dimension of the data space often brings the algorithms into the curse of dimensionality dilemma. In this paper, we present a novel approach to solve the supervised dimensionality reduction problem by encoding an image object as a general tensor of second or even higher order. First, we propose a discriminant tensor criterion, whereby multiple interrelated lower dimensional discriminative subspaces are derived for feature extraction. Then, a novel approach, called k-mode optimization, is presented to iteratively learn these subspaces by unfolding the tensor along different tensor directions. We call this algorithm multilinear discriminant analysis (MDA), which has the following characteristics: 1) multiple interrelated subspaces can collaborate to discriminate different classes, 2) for classification problems involving higher order tensors, the MDA algorithm can avoid the curse of dimensionality dilemma and alleviate the small sample size problem, and 3) the computational cost in the learning stage is reduced to a large extent owing to the reduced data dimensions in k-mode optimization. We provide extensive experiments on ORL, CMU PIE, and FERET databases by encoding face images as second- or third-order tensors to demonstrate that the proposed MDA algorithm based on higher order tensors has the potential to outperform the traditional vector-based subspace learning algorithms, especially in the cases with small sample sizes. PMID- 17283781 TI - Multigrid geometric active contour models. AB - Geometric active contour models are very popular partial differential equation based tools in image analysis and computer vision. We present a new multigrid algorithm for the fast evolution of level-set-based geometric active contours and compare it with other established numerical schemes. We overcome the main bottleneck associated with most numerical implementations of geometric active contours, namely the need for very small time steps to avoid instability, by employing a very stable fully 2-D implicit-explicit time integration numerical scheme. The proposed scheme is more accurate and has improved rotational invariance properties compared with alternative split schemes, particularly when big time steps are utilized. We then apply properly designed multigrid methods to efficiently solve the occurring sparse linear system. The combined algorithm allows for the rapid evolution of the contour and convergence to its final configuration after very few iterations. Image segmentation experiments demonstrate the efficiency and accuracy of the method. PMID- 17283782 TI - A segmentation model using compound Markov random fields based on a boundary model. AB - Markov random field (MRF) theory has been widely applied to the challenging problem of image segmentation. In this paper, we propose a new nontexture segmentation model using compound MRFs, in which the original label MRF is coupled with a new boundary MRF to help improve the segmentation performance. The boundary model is relatively general and does not need prior training on boundary patterns. Unlike some existing related work, the proposed method offers a more compact interaction between label and boundary MRFs. Furthermore, our boundary model systematically takes into account all the possible scenarios of a single edge existing in a 3 x 3 neighborhood and, thus, incorporates sophisticated prior information about the relation between label and boundary. It is experimentally shown that the proposed model can segment objects with complex boundaries and at the same time is able to work under noise corruption. The new method has been applied to medical image segmentation. Experiments on synthetic images and real clinical datasets show that the proposed model is able to produce more accurate segmentation results and satisfactorily keep the delicate boundary. It is also less sensitive to noise in both high and low signal-to-noise ratio regions than some of the existing models in common use. PMID- 17283783 TI - A nonparametric approach for histogram segmentation. AB - In this work, we propose a method to segment a 1-D histogram without a priori assumptions about the underlying density function. Our approach considers a rigorous definition of an admissible segmentation, avoiding over and under segmentation problems. A fast algorithm leading to such a segmentation is proposed. The approach is tested both with synthetic and real data. An application to the segmentation of written documents is also presented. We shall see that this application requires the detection of very small histogram modes, which can be accurately detected with the proposed method. PMID- 17283785 TI - Reconstructing dense light field from array of multifocus images for novel view synthesis. AB - This paper presents a novel method for synthesizing a novel view from two sets of differently focused images taken by an aperture camera array for a scene consisting of two approximately constant depths. The proposed method consists of two steps. The first step is a view interpolation to reconstruct an all-in-focus dense light field of the scene. The second step is to synthesize a novel view by a light-field rendering technique from the reconstructed dense light field. The view interpolation in the first step can be achieved simply by linear filters that are designed to shift different object regions separately, without region segmentation. The proposed method can effectively create a dense array of pin hole cameras (i.e., all-in-focus images), so that the novel view can be synthesized with better quality. PMID- 17283784 TI - Face verification with balanced thresholds. AB - The process of face verification is guided by a pre-learned global threshold, which, however, is often inconsistent with class-specific optimal thresholds. It is, hence, beneficial to pursue a balance of the class-specific thresholds in the model-learning stage. In this paper, we present a new dimensionality reduction algorithm tailored to the verification task that ensures threshold balance. This is achieved by the following aspects. First, feasibility is guaranteed by employing an affine transformation matrix, instead of the conventional projection matrix, for dimensionality reduction, and, hence, we call the proposed algorithm threshold balanced transformation (TBT). Then, the affine transformation matrix, constrained as the product of an orthogonal matrix and a diagonal matrix, is optimized to improve the threshold balance and classification capability in an iterative manner. Unlike most algorithms for face verification which are directly transplanted from face identification literature, TBT is specifically designed for face verification and clarifies the intrinsic distinction between these two tasks. Experiments on three benchmark face databases demonstrate that TBT significantly outperforms the state-of-the-art subspace techniques for face verification. PMID- 17283786 TI - Real-time system for high-image resolution disparity estimation. AB - We present the hardware implementation of a simple, fast technique for depth estimation based on phase measurement. This technique avoids the problem of phase warping and is much less susceptible to camera noise and distortion than standard block-matching stereo systems. The architecture exploits the parallel computing resources of FPGA devices to achieve a computation speed of 65 megapixels per second. For this purpose, we have designed a fine-grain pipeline structure that can be arranged with a customized frame-grabber module to process 52 frames per second at a resolution of 1280 x 960 pixels. We have measured the system's degradation due to bit quantization errors and compared its performance with other previous approaches. We have also used different Gabor-scale circuits, which can be selected by the user according to the application addressed and typical image structure in the target scenario. PMID- 17283787 TI - Inpainting of binary images using the Cahn-Hilliard equation. AB - Image inpainting is the filling in of missing or damaged regions of images using information from surrounding areas. We outline here the use of a model for binary inpainting based on the Cahn-Hilliard equation, which allows for fast, efficient inpainting of degraded text, as well as super-resolution of high contrast images. PMID- 17283788 TI - Ion recognition properties of self-assembled monolayers (SAMs). AB - In the search for new sensors, self-assembled monolayers (SAMs) have gained intensive interest due to their nanometre size, highly-ordered structures, and molecular recognition properties. This article presents an overview of ion recognition at SAM-modified surface/solution interfaces, and brings up to date the most notable examples for the sensing of cations and anions. Sensing is achieved with SAMs containing redox active and inactive receptors using techniques such as fluorescence spectroscopy, cyclic voltammetry and electrochemical impedance spectroscopy. PMID- 17283789 TI - Magnetic-fluorescent nanocomposites for biomedical multitasking. AB - Fluorescent magnetite nanocomposites based on magnetic nanoparticles, a polyhedral octaaminopropylsilsesquioxane and a porphyrin derivative have been prepared. The intracellular uptake of the nanocomposites by macrophage and bone osteoblast cells, and their potential as MRI contrast agents, has been demonstrated. PMID- 17283790 TI - Iron porphyrins catalyze the synthesis of non-protected amino acid esters from ammonia and diazoacetates. AB - Iron complexes of porphyrins (and corroles to a lesser extent) are the first catalysts to utilize ammonia for the synthesis of N-free amino acid esters. PMID- 17283791 TI - Triphasic liquid systems: generation and segregation of catalytically active Pd nanoparticles in an ammonium-based catalyst-philic phase. AB - A triphasic liquid system fabricated from isooctane, aqueous base, and trioctylmethylammonium chloride/decanol promoted the formation of Pd nanoparticles in the size range of 2-4 nm which remained immobilised in the onium phase, catalysed organic reactions, and could be recycled. PMID- 17283792 TI - Fibrous TiO2-SiO2 nanocomposite photocatalyst. AB - The electrospinning method is employed to prepare a fibrous TiO2-SiO2 (Ti : Si = 1 : 2) nanocomposite photocatalyst, in which Degussa P25 T i O2 nanoparticles are embedded inthe body of SiO2 fibers and which shows good photocatalytic activity due to its 3-D open structure, as evidenced by photocatalytic reduction of silver ions and decomposition of acetaldehyde. PMID- 17283793 TI - Coordination of oxovanadium(V) in an expanded porphyrin macrocyclet. AB - The formation of a dioxovanadium(V) complex of an expanded porphyrin-type Schiff base macrocycle is reported; the tetrapyrrolic ligand undergoes a tautomeric shift which permits a bimodal recognition of the nonspherical cationic guest. PMID- 17283794 TI - Mesoporous materials with zeolite framework: remarkable effect of the hierarchical structure for retardation of catalyst deactivation. AB - Hierarchical MFI zeolite was synthesized following a synthesis route using organic-inorganic hybrid surfactants; the resultant zeolite with mesoporous/microporous hierarchical structure exhibited remarkably high resistance to deactivation in catalytic activity of various reactions such as isomerization of 1,2,4-trimethylbenzene, cumene cracking, and esterification of benzyl alcohol with hexanoic acid, as compared with conventional MFI and mesoporous aluminosilicate MCM-41. PMID- 17283795 TI - Probing the substrate specificity of the catalytically self-sufficient cytochrome P450 RhF from a Rhodococcus sp. AB - Analysis of the substrate specificity of the self-sufficient cytochrome P450 RhF revealed that the enzyme tends to catalyse the dealkylation of substituted alkyl aryl ethers with shorter alkyl moieties more readily than equivalent compounds with longer alkyl groups. PMID- 17283796 TI - Mild and rational synthesis of palladium complexes comprising C(4)-bound N heterocyclic carbenes. AB - Oxidative addition of pyridyl-functionalised 4-iodoimidazolium salts to palladium(0) gives catalytically active complexes in which the N-heterocyclic carbene is bound to the palladium(II) centre in a non-classical bonding mode via C(4). PMID- 17283797 TI - Regioselectivity control of radiation-induced reaction: electron beam-induced fries rearrangement of sulfonamide within a beta-cyclodextrin inclusion complex. AB - EB (electron beam) irradiation of sulfonamide within a beta-cyclodextrin (beta CD) inclusion complex in the solid state induced the solvent-free Fries rearrangement, which proceeded at a shorter reaction time with reversed regioselectivity by inclusion into the beta-CD, compared with that of sulfonamide crystals; the beta-CD as a restricted nanospace had a large effect on the reactivity and regioselectivity of the solvent-free EB-Fries rearrangement. PMID- 17283798 TI - Rh(II)-catalysed room temperature aziridination of homoallyl-carbamates. AB - Rhodium(II) catalysts and PhIO in benzene convert homoallylic carbamates into the corresponding aziridines at room temperature. PMID- 17283799 TI - Mononuclear metavanadate catalyses gas phase oxidation of methanol to formaldehyde employing dioxygen as the terminal oxidant. AB - Multistage mass spectrometry experiments reveal a sequence of gas phase reactions for the oxidation of methanol to formaldehyde with a mononuclear oxo vanadate anion as the catalyst and dioxygen as the terminal oxidant. PMID- 17283800 TI - Synthesis of the spiroacetal-containing anti-Helicobacter pylori agents CJ-12,954 and CJ-13,014. AB - The first synthesis of the spiroacetal-containing anti-Helicobacter pylori agents ent-CJ-12,954 and ent-CJ-13,014 is reported based on the union of a heterocycle activated spiroacetal-containing sulfone fragment with a phthalide-containing aldehyde fragment; comparison of the 1H and 13C NMR data, optical rotations and HPLC retention times of the synthetic compounds (3S,2"S,5"S,7"S)-(1a) and (3S,2"S,5"R,7"S)-(2a) and the (3R)-diastereomers (3R,2"S,5"S,7"S)-(1b) and (3R,2"S,5"R,7"S)- (2b) with the naturally occurring compounds established that the synthetic isomers (1a) and (2a) were in fact enantiomeric to the natural products CJ-12,954 and CJ-13,014. PMID- 17283801 TI - Ring-opening polymerization of 3,6-dimethyl-2,5-morpholinedione with discrete amino-alkoxy-bis(phenolate) yttrium initiators: mechanistic insights. AB - Alkoxy-amino-bis(phenolate) yttrium amide and alkoxide complexes promote the ring opening polymerization of (3S,6S)-dimethyl-2,5-morpholinedione at 60-100 degrees C via a coordination-insertion polymerization mechanism. PMID- 17283802 TI - Click chemistry: a new facile and efficient strategy for preparation of functionalized HPLC packings. AB - Click chemistry has been successfully extended into the field of preparation of functionalized HPLC packings, proving a novel facile and efficient strategy for covalently bonding stationary phases onto HPLC grade silica beads; the potential has been demonstrated by the preparation of "Click I-IV" columns and preliminary results in the separation of sugars. PMID- 17283803 TI - Optical sculpture: controlled deformation of emulsion droplets with ultralow interfacial tensions using optical tweezers. AB - We report a technique for deforming micron-sized emulsion droplets that have ultralow interfacial tensions, by the manipulation of multiple optical trapping sites within the droplets. PMID- 17283805 TI - X-ray photoreduction of a di(mu-oxo)Mn(III)Mn(IV) complex occurs at temperatures as low as 20 K. AB - Full reduction of the Mn(III)(mu-O)2Mn(IV) core to Mn(II)(mu-OH2)2Mn(II) is observed upon irradiation by an X-ray beam at ca. 20 K. PMID- 17283804 TI - Phosphonopeptide K-26 biosynthetic intermediates in Astrosporangium hypotensionis. AB - Precursors and advanced intermediates for phosphonopeptide K-26 biosynthesis were synthesized and incorporation studies in Astrosporangium hypotensionis suggest a new mechanism of C-P bond formation in aromatic phosphonates. PMID- 17283806 TI - Synthesis of 1,1'-binaphthyls by photo-dehydro-Diels-Alder reactions. AB - 1,1'-Binaphthyls are prepared by a conceptually novel approach based on the photo dehydro-Diels-Alder reaction. PMID- 17283807 TI - Halide-free ethylation of phenol by multifunctional catalysis using phosphinite ligands. AB - The ortho-alkylation of phenols or aniline by catalytic C-H activation and multifunctional catalysis is described. PMID- 17283808 TI - Metal-free catalysis of sustainable Friedel-Crafts reactions: direct activation of benzene by carbon nitrides to avoid the use of metal chlorides and halogenated compounds. AB - The use of mesoporous graphitic C3N4 for the activation of benzene permitted to perform more sustainable Friedel-Crafts reactions by allowing to directly use carboxylic acids, alcohols and even quaternary ammoniums or urea as electrophiles. PMID- 17283809 TI - Solvent-free, heterogeneous photooxygenation of hydrocarbons by hyflon membranes embedding a fluorous-tagged decatungstate. AB - Hybrid fluoropolymeric membranes with 25% loading of the fluorous-tagged (RfN)4W10O32 effect the solvent-free photooxygenation of benzylic C-H bonds with up to 6100 TONs in 4 hours. PMID- 17283810 TI - Carbon nanotube-functionalized silicon surfaces with efficient redox communication. AB - Sidewall functionalized multi-walled carbon nanotubes can be covalently bound parallel to a silicon surface via a self-assembled acid-terminated monolayer used as an organic molecular glue. PMID- 17283811 TI - Organic-inorganic hybrid nanomaterial as a new fluorescent chemosensor and adsorbent for copper ion. AB - Functionalized silica nanotube (FSNT) possessing the phenanthroline moiety as a fluorescent receptor was fabricated by solgel reaction, and the binding ability of FSNT with metal ions was evaluated by fluorophotometry. PMID- 17283812 TI - The surprising and stereoselective formation of P2C10 cages by the reduction of Cp*PCl2. AB - Reactions of Cp*PCl2 with Group 13 reducing agents result in a cascade of P-C, P P and C-C bond forming reactions and the stereoselective formation of P2C10 cages. PMID- 17283813 TI - Alpha-lithio quinuclidine N-oxide (Li-QNO): a new base for synthetic chemistry. AB - A-Lithio quinuclidine N-oxide (Li-QNO) behaves as a strong non-nucleophilic base and an HMPA mimetic in a tandem process, in a range of synthetically useful reactions. PMID- 17283814 TI - Conversion of Cu2O nanocrystals into hollow Cu2-xSe nanocages with the preservation of morphologies. AB - With the use of PVP (polyvinylpyrrolidone) as capping reagent, cubic, octahedral and spherical Cu2O nanocrystals were obtained in aqueous media when different reducing agents were applied. After adding selenium sources at room temperature, these nanocrystals could be converted (based on the Kirkendall effect) into hollow Cu2-xSe nanocages that keep their corresponding orignial morphologies. PMID- 17283816 TI - Good out of HIV/AIDS? PMID- 17283817 TI - A primer on HIV/AIDS. PMID- 17283818 TI - Glimpses of HIV/AIDS around the globe. PMID- 17283819 TI - The faces of AIDS. PMID- 17283821 TI - Generating hope. PMID- 17283822 TI - Nicaragua: el segundo madre de mi corazon. PMID- 17283820 TI - Sexual practices and HIV: how can nurses respond? PMID- 17283823 TI - Eight advocacy roles for parish nurses. PMID- 17283824 TI - How did Jesus teach? PMID- 17283825 TI - Life and death disagreements. Interview by Susan A Salladay. PMID- 17283826 TI - Challenged by a smile. PMID- 17283827 TI - What are the spiritual needs of terminally ill patients? PMID- 17283828 TI - [Ion Juvara (1913 -1996)]. PMID- 17283829 TI - [A brief history about the setting up of the University of Medicine from Timisoara and of Second Department of Surgery]. PMID- 17283830 TI - [Professor Dr. Nicolae Angelescu--at age of 75 years]. PMID- 17283831 TI - Small-for-size graft injury in living donor adult liver transplantation. PMID- 17283832 TI - Complications of thyroid surgery. AB - Thyroid surgery has a history of significant changes in the technique and the incidence of complications. Since then continuous developments in surgical techniques and better understanding of thyroid anatomy and pathology have increased the safety of thyroid surgery and reduced the incidence of complications. Nowadays, the rate of postoperative mortality is extremely low. Nevertheless, the incidence of postoperative complications varies in literature from 7.4% to 53% of the operations performed. The most common and potentially life-threatening complications in thyroid gland surgery are vocal cord palsy and hypocalcemia. Herein we discuss the common complications in thyroid gland surgery and their proper management. PMID- 17283835 TI - Surgical treatment of severe acute pancreatitis. AB - Surgical treatment of severe necrotizing pancreatitis (SNP) is still controversial, inadequate indications and timing of operations being associated with high rates of mortality and morbidity. The aim of the present study is to analyze the indications and results of surgery in patients with SNP. Between 1989 and 2005, necrosectomy followed by open packing drainage (OPD) was performed in 80 patients with SNP. Timing of operations was individualized according to presence of pancreatic necrosis infection. Major postoperative complications were present in 34 patients (42.5%), pancreatic, enteric and biliary fistula, sepsis, iatrogenic bleeding and stress-ulcers being among the most frequently encountered. Secondary contamination of sterile pancreatic necrosis after OPD occurred in 13 patients (35.1%). The overall mortality rate was 32.5%, aggravation of MOF and septic shock being the main causes of death. Late surgical cure for OPD-related incisional hernia was required in 10% of the patients. Infection of pancreatic necrosis is an indication for urgent surgical necrosectomy and repeated re-debridements. Due to technical impossibility to perform adequate necrosectomy and the risk of MOF aggravation, early surgery is not recommended in patients with sterile necrosis. It should be postponed beyond the third week, when the biological condition of the patient is improved and delimitation of necrosis is complete. OPD is an adequate and efficient drainage procedure following necrosectomy. "Prophylactic" OPD for sterile necrosis is not recommended because it is associated with high morbidity rates and secondary infection of necrosis. PMID- 17283833 TI - [Retroperitoneal pyogenic infections with uncertain etiopathogenesis. Diagnostic and therapeutic difficulties]. AB - Retroperitoneal pyogenic collections can appear in most distinct pathological situations. Establishing the topography and pathogenic route are essential steps in developing the therapeutic attitude. Diagnosis of suppurative retroperitoneal process complicating a previously attested disease is less difficult. The challenges appears in that cases with atypical, clinical picture, which presents associated pathological states (diabetes mellitus, chronic alcoholism, behavioral disturbances), as well as in primary retroperitoneal infections (psoas abscess, infected retroperitoneal tumors) or in that situations in which the patient presents toxico-septic shock on admission. A retrospective study on the patients with retroperitoneal infections admitted in our Clinic between 1996 - 2006 was carried out. We selected the cases in which preoperative etiopathogenic diagnosis was uncertain (in some situations the exact etiopathogenic route remaining unknown even postoperatively). The aim of this study is to evaluate the factors contributing to this, and how therapeutic attitude was influenced. PMID- 17283834 TI - [The role of intraoperative ultrasound in the diagnosis and treatment of hydatid liver disease]. AB - Liver hydatid disease still represents a frequent condition in Romania, especially among population of Dobrogea County, which may lead to life threatening complications. To assess the role of intraoperative ultrasound (IOUS) in the diagnosis and treatment algorithms of liver hydatid disease. We could not find any similar studies in the literature in order to compare the results. The paper represents a retrospective study of IOUS performed for liver hydatid disease on a group of 43 patients admitted in the 2nd Clinic of Surgery - Clinical Emergency Hospital of Constanta. IOUS was intraabdominal (36 cases), transdiaphragmatic (7 cases) and was able to diagnose infected liver HC (7 cases), locate bilio-cystic fistulas (6 cases), hydatic cysts (18 cases) or relation with important anatomic elements (12). Ultrasound-guided frenotomy was performed in 5 cases and ultrasound-guided puncture in 9 cases. In 26 out of 43 patients (60.47%), IOUS influenced decision making during surgery. These data recommends IOUS in managing hydatid disease, allowing a complete diagnosis and optimal treatment, thus reducing postoperative morbidity. PMID- 17283836 TI - [Severity factors of acute renal failure in severe acute pancreatitis]. AB - AIM: assessment of the severity factors of the acute renal failure (ARF) in the severe acute pancreatitis (SAP). 28 (32.55%) severe acute pancreatitis with acute renal failure (19 males and 9 females, aged between 30 and 67), treated by hemodialysis, selected from 86 severe acute pancreatitis with acute renal failure, admitted in the Hemodialysis Department of ICU in the last 6 years, were analyzed. The severity of the pancreatitis was assessed using the following criteria: clinico-biologic scores (Ranson > 3 and APACHE II > 8), the CT-scan (Balthazar score D and E and CTSI > 4), the presence of the organ and system dysfunctions assessed by Tran and Cuesta criteria and the presence of the abdominal compartment syndrome (abdominal pressure > 25 mm Hg). 8 dialyzed cases (28.5%) were operated on: 2 cholecystostomy, 2 cholecystectomy+choledocho lithotomy+T tube drainage, 4 exploring laparotomy + drainage. RESULTS: The following severity factors were identified: 1. the association of the ARF with other system and organ dysfunctions, the highest mortality rate being provided by the following associations: ARF + more than 3 organ and system dysfunctions and ARF + ARDS in assisted ventilated patients; 2. the abdominal compartment syndrome with abdominal pressure > 25 mm Hg; 3. severe sepsis and altered biological status of the patients. We registered a general mortality rate of 53.57% (15 deaths) and a postoperative mortality rate of 75% (6 deaths from 8 operated patients). CONCLUSIONS: 1. Summing up the pathologic changes proper to the acute pancreatitis (enzymes and mediators releasing) with sepsis and abdominal compartment syndrome worsens the humoral and metabolic syndrome of the ARF. 2. The simultaneous presence of other organ and system dysfunctions makes the ARF in SAP one of the most severe forms. 3. ARF with anuria + ARDS in assisted ventilated patients and ARF + more than 3 associated organ and system dysfunctions are the clinical forms with the highest mortality rate. 4. The abdominal compartment syndrome is an important severity factor of the ARF because of its direct impact against the kidney and the organ and system dysfunctions which produces and worsens. PMID- 17283837 TI - [Activated recombinant factor VII (Novoseven) in multiple trauma patients: an outcome analysis]. AB - BACKGROUND AND OBJECTIVE: In multiple trauma patient the bleeding is a major cause of death and it is caused by vascular injury or post-traumatic coagulopathy. Regardless of etiology, management of massive bleeding requires immediate surgery to stop bleeding with simultaneous stabilization of hemostasis and maintenance of normovolemia. The objective was to evaluate the efficacity and safety of recombinant activated factor VII in patients with massive posttraumatic hemorrhage after failure of conventional methods to control bleeding (surgical haemostasis, volemic resuscitation, transfusions, rewarming). METHODS: 34 multiple trauma patients with severe hemorrhage requiring > 10 transfusion units of packed red cells received recombinant activated factor VII. Postdrug transfusion requirements were assessed (red packed cells, fresh frozen plasma, platelet concentrations and cryoprecipitate), and mortality was compared with predicted outcomes, using Injury Severity Score, Revised Trauma Score and Trauma Score-Injury Severity Score. We also noted the incidence of adverse effects, mostly thromboembolic events. We use a special design chart to follow the patients who received rFVIIa. RESULTS: We have the following results: the mortality rate was reduced (without statistical relevance), the coagulation times also reduced--aPTT decreases from 76 s to 38.5 (p = 0.000), PT from 23 s to 18 s (p = 0.000), transfusion requirements decrease- RPCs from 11.5 units to 3 units (p = 0.000), FFP from 7.5 units to 2 units (p = 0.000). We analysed the cases with adverse effects but we didn't find a direct cause- effect explication. CONCLUSIONS: The rFVIIa is efficient in post-trauma-tic bleeding (decrease transfusion requirements, normalized coagulation times), reduce mortality rate. PMID- 17283838 TI - [Pancreaticoduodenectomy]. PMID- 17283839 TI - [Colonic angiodysplasia in a chronic renal failure patient]. AB - An important cause of intestinal bleeding in patients with chronic renal failure is angiodysplasia. In retrospective reports up to 19-32% of patients had bleeding from angiodysplastic lesions. These are usually multiple, have a high tendency of rebleeding (25-47%) and are often located in the stomach and duodenum, but can affect the colon and the jejunum as well. Bleeding from angiodysplastic lesions is usually low grade and stops spontaneously in more than 90% of patients, but some times may be life threatening necessitate therapeutic interventions to achieve hemostasis. We report a case of an 18-year old female with renal failure on CAPD who presented a massive lower gastrointestinal bleeding and imposed emergency surgery. PMID- 17283840 TI - Upper gastrointestinal bleeding due to primary aortoenteric fistula. AB - Primary aortoenteric fistula (PAEF) is a rare but clinically important cause of catastrophic gastrointestinal bleeding. "Herald bleeding" is a characteristic symptom which refers to specific case of upper gastrointestinal bleeding that stop temporarily spontaneously and then proceeds to massive bleeding. We present the case report of a 55-year-old male with PAEF who was admitted due to upper gastrointestinal bleeding. Endoscopic studies were unremarkable and patient underwent exploratory laparotomy. The postoperative course was uneventful. A high index of suspicion, early diagnosis and prompt appropriate surgical intervention are crucial for survival of patient with PAEF. Gastrointestinal bleeding combined with a negative endoscopy suggests PAEF. Endovascular operation is an attractive treatment option. PMID- 17283841 TI - [Gastric volvulus--complication of a large paraesophageal hiatal hernia]. AB - The authors present the case of a patient with a large paraesophageal hiatal hernia complicated with organo-axial gastric volvulus. We discuss problems of diagnosis and therapeutical options. PMID- 17283844 TI - The increasing need for long-term care information systems. PMID- 17283843 TI - [Telescopic anastomosis in colorectal surgery]. AB - The most frequent postoperative morbidity and mortality in the colorectal surgery is caused by the failure of the anastomosis. On the base of the statistics the postoperative mortality caused by the failure of the anastomosis can rise up to 20%. In the last decade a lot of types of anastomoses was initiated, for example: telescopic anastomosis, mechanical anastomosis with stapler, anastomosis with a bio-fragmentary ring. In the technique of the telescopic anastomosis, introduced from the beginning of 20th century, many changes had made. The experimental and the operative results shown that the telescopic anastomosis is a secure, fast and cheap procedure in the surgery of the colon. CONCLUSIONS: the telescopic anastomosis is applicable also in emergency, with a short septic time , easy procedure and doesn't need special instruments. PMID- 17283842 TI - [Malignant peritoneal mesothelioma]. AB - Mesothelioma is a neoplasm originating from the mesothelial surface lining cells of the serous human cavities. It may involve the pleura, less frequently the peritoneum rarely, the pericardium, the tunica vaginalis testis and ovarian epithelium. Asbestos has been widely used in industry. A causal relationship between asbestos exposure and pleural, peritoneal and pericardial malign mesothelioma was suggested, the risk of cancer being correlated to cumulate exposure. Studies from National Cancer Institute, USA, show that the malignant mesothelioma is a rare and aggressive asbestos related malignancy. The symptomatology is insidious and poses difficult problems in diagnosis and treatment. This paper presents the case of a 59 year old patient with malignant peritoneal mesothelioma who worked almost 40 years as an electrician, exposed to asbestos fibers. He was hospitalized for important weight loss, abdominal pain and tiredness being diagnosed after imaging tests with a giant tumor, localized at the abdominal upper level, which seems to originate from the spleen's superior pole. During surgery we discovered a tumor with cystic parts, intense vascularized, which turn to be adherent in the upper side to the lower face of the left midriff cupola, to the spleen superior pole and 1/3 middle level of the great gastric curve. It was performed surgical ablation of the tumor, splenectomy with favorable postoperative evolution, the patient being now under chemotherapy treatment. PMID- 17283845 TI - Obtaining board support for long-term care information system initiatives. PMID- 17283846 TI - The VAST (Vencor Admission Screening Tool) program: helping make better referral decisions. PMID- 17283847 TI - Can technology help Aunt Nellie?: coordinating care and services for those we care about most. PMID- 17283848 TI - Information systems strategy development and implementation: a nursing home perspective. PMID- 17283850 TI - An extranet provides services to the medical industry: a case study for health plans. PMID- 17283849 TI - Using Intranets in healthcare. PMID- 17283851 TI - Information at the point of care: effect on patient care and resource consumption. PMID- 17283852 TI - Asking the how questions: quantifying group processes behaviors. AB - The authors analyzed the group work behaviors of 132 grade school students to assess behavioral manifestations of group processes. The authors coded videotapes of students working together on a math-learning task to quantify the incidence of microbehaviors associated with process loss and process gain (I. D. Steiner, 1972). Factor analysis of 11 categories of coded behaviors revealed 3 factors that accounted for 67% of the explained variance. The factors were interpretable as process gain (PGV), process loss behavior directed outside the group (PLV out), and process loss behavior directed into the group (PLV-In). The authors discuss correlations among variables derived from the factors and with other measures. Results support this method of quantifying group processes. The authors considered implications for the broader study of group processes. PMID- 17283853 TI - Memory for emotionally arousing stimuli: a comparison of younger and older adults. AB - The authors compared emotional memory in younger (aged 18-32 years) and older (aged 59-84 years) adults. Previous researchers who investigated the emotionmemory relationship in younger adults consistently showed that emotional arousal enhances memory for central detail. The present authors' goal was to determine whether a similar effect could be found with older adults. Younger and older adults viewed a series of 12 slides, accompanied by a taped narrative, that showed emotionally arousing or neutral scenes in the middle phase (Slides 5-8). Participants then completed recognition tests that were scored for central detail, peripheral detail, and gist. The results indicated that, although younger adults showed higher performance than older adults did, both groups showed increased memory for central detail. In contrast, the authors found no such enhancement for peripheral detail or gist in either group. These results indicated that the arousal manipulation produced a similar effect on memory in younger and older adults. Furthermore, these results were consistent with the notion of poststimulus elaboration, which is the continued processing of central detail after the termination of an arousing event. PMID- 17283854 TI - Age and individual differences in working memory: the size judgment span task. AB - The authors introduced the Size Judgment Span (SJS) task, a working memory measure developed for use with persons of varied educational backgrounds and general intellectual ability. The authors pooled data from 5 published articles where the SJS task and other measures of cognitive performance were administered to create an archival data set with 496 participants. Analyses of these data yielded strong evidence of age and individual ability differences in SJS performance, confirming the sensitivity of this task for empirically distinguishing age and ability groups. The SJS was also significantly correlated with the backward digit span and listening span tasks. Using hierarchical regression analyses, the authors examined the SJS task as a predictor of different forms of episodic memory, including spatial location memory, verbal free recall, and recognition memory. Results confirmed the practical utility and predictive validity of the SJS task. The authors considered implications for current theoretical views of working memory. PMID- 17283855 TI - Reactions to heard words: varying emotional content and frequency of exposure. AB - The authors aurally presented words varying in emotional content and frequency of exposure to 56 participants during (a) a study phase in which 288 words (72 separate words with repetitions) were presented and (b) a test phase in which participants were presented with the 72 words from the study phase along with 24 new words. In the test phase, participants responded to these 96 words with either a recognition response or a likability response. The recognition results indicated that increased exposure produced increased recognition; however, high arousal and negative valence words produced higher false positive scores. The likability scores revealed an overall mere exposure effect (MEE). However, words of low arousal and of positive valence did not show the MEE. PMID- 17283856 TI - Perceptual learning on inspection time and motion perception. AB - Perceptual learning on simple perceptual tasks is interpreted as plasticity of neuronal populations in the sensory cortex (M. Fahle & T. Poggio, 2002). The authors examined individual differences on perceptual learning for 2 tasks inspection time (IT) and a motion direction discrimination task that was instantiated as random dot kinematograms. The authors' main questions were whether individual differences in perceptual learning were consistent across the 2 tasks and whether perceptual learning correlated with cognitive abilities test scores. In all, 56 young adults completed 16 threshold estimations on 1 of 2 orthogonal versions of each task. Then, the authors made 2 further threshold estimations for the untrained, orthogonal version. Participants also completed a battery of 6 cognitive abilities tests that measured fluid ability (Gf) and perceptual speed (Gs). Perceptual learning was demonstrated for both tasks, but the degree of learning across tasks was not characteristic of the individual. Learning on IT correlated with Gs (r = .35), but learning on the motion direction discrimination task was unrelated to cognitive ability. Correlations of IT with cognitive measures were stable over the training period. IT was correlated with both the motion direction discrimination task (r = -.39) and an unmasked line length judgment task (r = -.31). The authors concluded that perceptual learning on IT correlates with cognitive abilities test scores, that correlations of IT with cognitive abilities test scores are stable as task performance improves with practice, and that the IT task is psychologically complex. PMID- 17283857 TI - Measuring the executive regulation of emotion with self-rating scales in a nonclinical population. AB - Prefrontal systems play an important role in the regulation of emotion as evidenced by clinical neuroimaging studies. Both subjective and objective neuropsychological tests provide functional evidence of executive dysfunction in emotional deregulation. The present authors evaluated these relationships here in a nonclinical community sample using the Frontal Systems Behavior Scale, Profile of Mood States (POMS), and Depression Anxiety Stress Scales (DASS). Positive correlations uniformly emerged between prefrontal system dysfunction and negative emotional states (anger, depression, anxiety, stress, confusion, and fatigue), whereas positive emotion (vigor) showed a modest inverse correlation with prefrontal system dysfunction, even after control for demographic influences. These relationships may result from cognitive strategies for managing emotion mediated by reciprocal connections between prefrontal systems and the limbic system. The findings corroborated those of other methodologies, supporting the Frontal Systems Behavior Scale (FrSBe) as a valid tool to measure prefrontal function in nonclinical populations. PMID- 17283858 TI - Alpha-glucosidase inhibitors: new therapeutic agents for chronic heart failure. PMID- 17283859 TI - Role of NAD(P)H oxidase and its regulation in chronic hypertension. PMID- 17283860 TI - Stem cells and kidney disease. AB - Functional recovery in acute renal failure is well known, and the adult kidney is generally recognized to have the capacity to regenerate and repair. Several groups have reported the contribution of bone marrow-derived cells in this process, and others have confirmed the existence of adult stem cells in the kidney, including slow-cycling cells, side population cells, CD133+ cells and rKS56 cells. However, recent data demonstrated that in vivo differentiation of bone marrow-derived cells into renal tubular cells may not occur at all, or is at most a minor component of the repair process. Moreover, it is now generally accepted that stem cells and multipotent cells contribute to the regenerative process by producing protective and regenerative factors rather than by directly differentiating to replace damaged cells. Therefore, for clinical regenerative medicine in kidney disease, the focus of stem cell biology will shift from multiple differentiation of cells or cell-therapy to multiple functions of the cells, such as the production of bone morphologic protein-7 and other regenerative factors. PMID- 17283861 TI - Interaction of angiotensin I-converting enzyme insertion-deletion polymorphism and daily salt intake influences hypertension in Japanese men. AB - The contribution of angiotensin I-converting enzyme insertion-deletion polymorphism (ACE I/D) to salt-sensitivity hypertension has been extensively studied by means of salt-loading tests, but whether or not the interaction with daily salt intake affects blood pressure still remains to be clarified. We therefore conducted a cross-sectional study of 284 Japanese male workers (age range, 20-64 years) to examine the effect of ACE I/D genotype and daily salt intake on hypertension. Blood pressure was measured and the ACE I/D was identified by polymerase chain reaction (PCR). Daily salt intake was calculated from a food frequency questionnaire (FFQ). In multivariate analyses, we explored the interaction of ACE I/D and salt intake by means of logistic regression analysis and multiple linear regression analysis. ACE I/D per se was not associated with blood pressure levels or hypertension. ACE I/D interacted with daily salt intake and correlated with hypertension (p for interaction = 0.047). In the ID+II genotype, hypertension was increased by high salt intake (p = 0.005), while in the DD genotype it was not (p = 0.257). The interaction was more prominent in the overweight group (p = 0.039) than in non-overweight group. In the overweight group, high salt intake induced a 10.5 mmHg higher diastolic blood pressure in the ID+II genotype than in the DD genotype (p = 0.042). Our results suggest that ACE I/D and daily salt intake constitute a gene-environment interaction, which may be further modulated by overweight. PMID- 17283862 TI - Age-related reduction of systemic arterial compliance relates to decreased aerobic capacity during sub-maximal exercise. AB - A decrease in systemic arterial compliance (SAC) increases left ventricular load along with the demand for excessive myocardial oxygen consumption when the age related reduction of SAC reaches a marked level, and consequently may depress left ventricular pump function. Reduced left ventricular pump function decreases aerobic capacity, and some study groups have shown that SAC and/or central arterial distensibility is correlated with maximal aerobic capacity in humans. We thus hypothesize that, once the age-related reduction of SAC reaches a marked level, the participation of SAC in aerobic capacity will be significant even during sub-maximal exercise. Thirty young humans and 46 elderly humans participated in this study. SAC, oxygen uptake at the ventilatory threshold (VO2VT), and the ratio of increase in oxygen uptake, in cardiac output, and in effective arterial elastance to increase in work rate (deltaVO2/deltaWR, deltaCO/deltaWR and deltaEa/deltaWR) were measured. SAC was significantly higher in young subjects compared with elderly subjects, and was significantly related to VO2VT in elderly subjects. SAC also significantly correlated with deltaVO2/deltaWR, deltaCO/deltaWR and deltaEa/deltaWR in elderly subjects. When total subjects were divided by the value of SAC into 6 groups, the VO2VT values in the 3 groups with lower SAC were significantly lower than those in the 3 groups with higher SAC, and gradually decreased with the reduction of SAC. There were no changes in VO2VT among the 3 groups with higher SAC. These results suggest that the participation of SAC in aerobic capacity is significant even during sub-maximal exercise in individuals who show a pronounced age-related reduction of SAC. PMID- 17283863 TI - Efficacy of azelnidipine on home blood pressure and pulse rate in patients with essential hypertension: comparison with amlodipine. AB - Recently it has been recognized that not only blood pressure (BP) but also pulse rate (PR) assessed in the setting of the patient's home by a home BP monitoring device has higher predictive power for cardiovascular events than similar measurements made in the office setting. In this study, we compared the efficacy of azelnidipine to that of amlodipine in lowering morning BP and reducing PR in outpatients with essential hypertension. Patients were assigned to receive once daily administration of azelnidipine 8-16 mg/day (n = 54) or amlodipine 2.5-5 mg/day (n = 54) for 8 weeks. Morning BP and PR were evaluated by assessing patients' self-monitored BP and PR in the home environment. The mean reductions of morning systolic/diastolic BP (SBP/DBP) in the azelnidipine and amlodipine groups were similar (-24.1 +/- 11.8/-14.1 +/- 10.7 vs. -20.4 +/- 11.7/-12.2 +/- 7.7 mmHg). However, whereas azelnidipine decreased mean PR by -6.4 +/- 8.3 beats/min (p < 0.05 vs. baseline), amlodipine did not cause significant reduction of this parameter (-2.1 +/- 8.2 beats/min). Although neither drug changed PR in patients in whom baseline PR was < 70 beats/min, azelnidipine significantly lowered PR in patients whose baseline PR was > 70 beats/min. These results suggest that oral azelnidipine administration may be an effective therapy in the setting of chronic morning hypertension as well as for home PR control. PMID- 17283865 TI - The association between morning hypertension and metabolic syndrome in hypertensive patients. AB - Morning hypertension (MHT) and metabolic syndrome (MS) have been reported as important risk factors for stroke and cardiovascular events. We investigated the prevalence of MHT and MS among hypertensive patients in our outpatient clinic from June to August, 2005. We studied 181 hypertensive patients (91 men and 90 women) in our outpatient clinic using home-use electronic sphygmomanometers. Seventy-nine of these 181 patients (43.6%) demonstrated MHT, defined as systolic blood pressure (SBP) > or = 135 mmHg in the morning. Only 48.1% of the patients demonstrated normal SBP both at the clinic and in the morning at home, whereas 72.9% of the patients demonstrated normal diastolic blood pressure (DBP) under the same conditions. Sixty-one patients (33.7%) had MS, and 34 patients had both MHT and MS. Twenty-seven of the 102 patients (26.5%) without MHT had MS. The frequency of MS was significantly higher among those with MHT than those without MHT (p = 0.019). Multiple logistic regression analysis including smoking, alcohol consumption, sex, and age as confounding factors showed significant association between MHT and MS (odds ratio: 1.99; 95% confidence interval: 1.04-3.80; p = 0.039). In conclusion, although 1 year has passed since the JSH 2004 guidelines, 43.6% of our patients still showed MHT, and there was a significantly higher prevalence of MS among those with MHT. Our results suggest the need for a more vigorous intervention for controlling BP. PMID- 17283864 TI - Abnormal glucose tolerance contributes to the progression of chronic heart failure in patients with dilated cardiomyopathy. AB - Since 1) dilated cardiomyopathy (DCM) causes chronic heart failure (CHF), and 2) augmentation of neurohumoral factors such as angiotensin II impairs glucose metabolism, we examined the rate of abnormal glucose metabolism in patients having both DCM and CHF and whether correction of the impairment of glucose metabolism would improve the pathophysiology of CHF in DCM patients. A 75-g oral glucose tolerance test (OGTT) was performed in 56 patients with DCM-induced CHF and 168 age- and sex-matched control subjects. Among the CHF patients, 26.8% and 50.0% suffered from diabetes mellitus (DM) and impaired glucose tolerance (IGT), respectively, showing that abnormal glucose tolerance was more prevalent in DCM patients than in the control subjects (7.7% and 14.3%, respectively). In the patients with DCM-induced CHF, a correlation was observed between the brain natriuretic peptide (BNP) levels and the difference between the plasma glucose levels at the time of fasting and at 2 h of OGTT. Since neither DM nor IGT are thought to cause DCM, the abnormalities of glucose metabolism may be attributed to the progression of CHF. Furthermore, we tested whether correction of the abnormal glucose tolerance using voglibose (an alpha-glucosidase inhibitor) would improve the severity of CHF in another group of 30 patients with DCM-induced CHF and IGT. The patients treated with voglibose for 24 weeks showed decreases in left ventricular dimension, NYHA functional classification values, and plasma BNP levels, and an improvement in cardiac function. In conclusion, abnormal glucose tolerance was more prevalent among patients with DCM-induced CHF than controls, and the correction of IGT improved the pathophysiology of CHF. PMID- 17283866 TI - Controlled release nifedipine and valsartan combination therapy in patients with essential hypertension: the adalat CR and valsartan cost-effectiveness combination (ADVANCE-combi) study. AB - This study was designed to compare the clinical efficacy of two calcium channel blocker-based combination therapies with an angiotensin receptor blocker in Japanese patients with essential hypertension. A 16-week, double-blind, parallel arm, randomized clinical trial was performed to compare the efficacy and safety of the combination therapy of controlled release nifedipine (nifedipine CR) plus valsartan vs. that of amlodipine plus valsartan. The primary endpoint was the target blood pressure achievement rate. Eligible patients were randomly allocated to nifedipine CR-based or amlodipine-based treatment groups. Patients were examined every 4 weeks to determine whether the blood pressure had reached the target level. When the target level was not achieved, the drug regimen was changed; when the target blood pressure was achieved, the same study medication was continued. A total of 505 patients were enrolled in the study (nifedipine CR group: 245 cases; amlodipine group: 260 cases). After 16 weeks of treatment, blood pressure was significantly reduced in both groups, but to a larger extent in the nifedipine CR group than in the amlodipine group (p < 0.01). The target blood pressure achievement rate was also significantly higher in the nifedipine CR group (p < 0.001). There was no significant difference in the incidence of drug-related adverse events between the groups. These results indicate that the nifedipine CR-based combination therapy was superior to the amlodipine-based therapy for decreasing blood pressure and achieving the target blood pressure in patients with essential hypertension. PMID- 17283867 TI - Inhibition of nitrate tolerance without reducing vascular response during eccentric dosing of nitrates. AB - It has been reported that the nitrate tolerance related to continuous dosing of nitrates reduces drug efficacy, and therefore eccentric dosing of nitrates is recommended. In this study, we investigated the appearance of nitrate tolerance related to continuous dosing of nitrates and prevention of nitrate tolerance during eccentric dosing by comparing the grade of coronary dilatation after sublingual nitroglycerin. Of 26 patients with ischemic heart disease who underwent elective cardiac catheterization, 8 patients were continuously administered nitrates, 8 patients were eccentrically administered nitrates, and 10 patients were not treated. We compared the coronary response to sublingual nitroglycerin among the 3 groups. In a coronary vessel without significant stenosis, the coronary vessel area, coronary lumen area, and mean coronary blood flow velocity after sublingual nitroglycerin were measured using intravascular ultrasound (IVUS). In the continuous dosing group, the maximal rate of change in the vessel area after sublingual nitroglycerin was 105 +/- 1 (mean +/- SEM) %, significantly lower than those in the untreated group and the eccentric dosing group (114 +/- 2%, 114 +/- 2%) (p < 0.01, respectively). In conclusion, eccentric dosing of nitrates inhibited the appearance of nitrate tolerance without reducing vascular response. PMID- 17283868 TI - An alpha1-receptor blocker reduces plasma leptin levels in hypertensive patients with obesity and hyperleptinemia. AB - Obesity is often complicated by hypertension, and both conditions are risk factors for atherosclerosis. Leptin has attracted attention as a possible cause of hypertension in obese persons. We investigated the effect of a slow-release alpha1-receptor blocker, bunazosin hydrochloride, on leptin levels and insulin resistance in obese hypertensive patients with hyperleptinemia. The subjects were 17 patients (12 men and 5 women aged 56.1 +/- 12.2 years) with essential hypertension who were not receiving alpha1-receptor blockers. They had a body mass index (BMI) > or = 25 kg/m2 and a plasma leptin concentration > or = 5 ng/ml. They received oral therapy with bunazosin hydrochloride at doses of up to 9 mg/day. The plasma leptin concentration, body weight, blood pressure, heart rate, fasting blood glucose, plasma insulin concentration, and free fatty acid level were compared between before and after treatment. Although there was no significant change of BMI, there was a significant decrease of plasma leptin after treatment (10.6 +/- 5.4 ng/ml vs. 8.7 +/- 3.4 ng/ml, p = 0.0128), as well as a significant decrease of plasma insulin (9.8 +/- 4.8 microU/ml vs. 8.1 +/- 4.6 microU/ml, p = 0.0494) and HOMA-R (2.9 +/- 2.1 vs. 2.2 +/- 1.5, p = 0.0237). In conclusion, bunazosin hydrochloride reduced the plasma leptin level and improved insulin resistance in hypertensive patients with obesity and hyperleptinemia. PMID- 17283871 TI - [Progression on vascular hyporesponsiveness after shock]. PMID- 17283872 TI - [Status of shock resuscitation by the standard of evidence-based medicine]. PMID- 17283869 TI - Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: involvement of the renin-angiotensin system. AB - Although vascular cells express multiple members of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic hypertension have remained unclear. Thus, we quantified the mRNA expressions of these NAD(P)H oxidase components by real-time polymerase chain reaction and evaluated superoxide production and morphological changes in the aortas of 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar Kyoto rats (WKY). The aortic media of SHRSP had an approximately 2.5-fold greater level of Nox4 mRNA and an approximately 10-fold greater level of Nox1 mRNA than WKY. The mRNA expressions of gp91phox and p22phox in SHRSP and WKY were comparable. SHRSP were treated from 24 weeks of age for 8 weeks with either high or low doses of candesartan (4 mg/kg/day or 0.2 mg/kg/day), or a combination of hydralazine (30 mg/kg/day) and hydrochlorothiazide (4.5 mg/kg/day). The high-dose candesartan or the hydralazine plus hydrochlorothiazide decreased the blood pressure of SHRSP to that of WKY, whereas the low-dose candesartan exerted no significant antihypertensive action. Media thickening and fibrosis, as well as the increased production of superoxide in SHRSP, were nearly normalized with high-dose candesartan and partially corrected with low-dose candesartan or hydralazine plus hydrochlorothiazide. These changes by antihypertensive treatment paralleled the decrease in mRNA expression of Nox4 and Nox1. These results suggest that blood pressure and angiotensin II type 1 receptor activation are involved in the up regulation of Nox1 and Nox4 expression, which could contribute to vascular injury during chronic hypertension. PMID- 17283873 TI - [To further widening the thoughts about trauma repair and tissue anagenesis]. PMID- 17283870 TI - Human urotensin-II potentiates the mitogenic effect of mildly oxidized low density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide. AB - Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents. PMID- 17283874 TI - [To strengthen the study on the comprehensive management of burn shock]. PMID- 17283875 TI - [Evaluation of effectiveness and safety of a new hydroxyethyl starch used in resuscitation of burn shock]. AB - OBJECTIVE: To evaluate the effectiveness and safety of hydroxyethyl starch (HES 130/ 0.4, 60 g/L) in resuscitation during shock stage of burns. METHODS: Sixty six burn patients who were admitted to hospital within 2 hours after burn injury requiring fluid resuscitation were enrolled into this study, and they were randomized into HES( n = 33, with HES as a component of fluid resuscitation) and plasma (P, n = 33, with plasma as a component of fluid resuscitation) groups. HES or plasma was given as colloid within 48 postburn hours (PBH), and only albumin [( 111 +/- 4) , ( 105 +/- 5 ) g for each group] were given to the patients during 3 to 7 postburn days (PBD). Heart rate, blood pressure, central venous pressure (CVP) , urine output per hour were measured, gain/loss of body fluid during the first and second 24 PBH were recorded, serum total protein, albumin, hemoglobin( Hb) , prothrombin time (PT) , fibrinogen; platelet ( PLT) , as well as liver and renal function, allergy and bleeding tendency were determined and observed at corresponding time-points. RESULTS: There were no obvious differences in heart rate, blood pressure, CVP and urine output per hour within 24 PBH between the two groups (P > 0.05). Also there was no difference in gain/loss of body fluid during the first and second 24 PBH. The content of hemoglobin on 1 ,3, 7,14 PBD ,and the PT, the content of fibrinogen, the number of PLT on 1,3,14 PBD also exhibited no difference between the two groups (P > 0.05). The serum contents of total protein and albumin in HES group were [(31 +/- 3) g/L, (30 +/- 3)g/L ] on 1 PBD, and [(20.4 +/- 3.6) g/L, (18.4 +/-2.3) g/L] on 3 PBD, which were obviously lower than those in P group [(45 +/- 4) g/L, (39 +/- 3) g/L on 1 PBD, and 1 (24.5 +/- 4.3) g/L, (21.3 +/- 3.9) g/L) on 3 PBD, (P <0. 01). Though the serum content of albumin on 7 PBD was similar in the two groups (P > 0.05), the serum total protein in HES group (40 +/- 4) g/L was markedly lower than that in P group [(45 +/- 4) g/L, P < 0.01] . Within 7 PBD, no abnormal bleeding was found in the two groups, and the liver function and renal function were similar. There were 4 cases showing allergic reaction in plasma group while none in HES group. CONCLUSION: New type of HES can partially substitute plasma and be used in fluid resuscitation for burn patients. However, plasma protein replenishment should still be emphasized. PMID- 17283876 TI - [The influence of changes in the levels of calcitonin gene-related peptide and neuropeptide Y on cardiac function of severe burn patients during shock stage]. AB - OBJECTIVE: To investigate the influence of the changes in the levels of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) on cardiac function of severe burn patients during shock stage. METHODS: Sixty severe burn patients with total burn surface area larger than 30% were enrolled as experiment group (E group) , and they received fluid resuscitation and debridement during shock stage. Sixty healthy volunteers were enrolled as control group (C group). The changes in the plasma level of CGRP, NPY and cTnT in E and C groups were observed at 1, 3, 6, 12, 24, 48 post-burn hours (PBH). The correlation among the CGRP, NPY and cTnT in the C group were analyzed. RESULTS: At 3 PBH, the plasma level of CGRP in E group (28 +/- 6) ng/L was lower than that in C group (55 +/- 7) ng/L , and it reached the lowest level at 12 PBH (15 +/- 4)ng/L . It was still lower than that in C group at 48 PBH (P < 0.05). The levels of NPY and cTnT in E group were significantly increased at 1PBH [(136 +/- 20) ng/L, (0.41 +/- 0.08) microg/L] compared with that in C group[ (86 +/- 13) ng/L, (0.16 +/- 0.06) microg/L], peaking at 12PBH [(189 +/- 31) ng/L, (1.78 +/- 0. 47) microg/L], and remaining higher than those in C group at 48PBH. There exhibited obvious negative correlation between the changes in the level of CGRP and cTnT ( r = -0.76, P < 0.01), while obvious positive correlation was found between the changes in level of NPY and cTnT ( r = 0.79, P < 0.01). CONCLUSION: The decrease in CGRP level and the increase in NPY level might play important roles in myocardial injury during shock stage of severe burn patients. PMID- 17283877 TI - [Analysis of correlation factors affecting the incidence of burn shock]. AB - OBJECTIVE: To analyze the correlation factors affecting the incidence of burn shock, so as to provide guidance for the clinical treatment of shock after burns. METHODS: Retrospective analysis of clinical data of 15 624 patients hospitalized in our department from 1973 to 2005 was undertaken . The incidence of shock during every 10 years, as well as the relationship between shock incidence and age, burn area, interval between injury and hospitalization, and complications were analyzed statistically. RESULTS: The incidence of shock during 1973-1980, 1981-1990, 1991-2000 and 2001-2005 periods was 14.69%, 13.50%, 9.38% and 7.88%, respectively, and there was significant difference of shock incidence between each 10 years and its succeeding period (P < 0.01). The occurrence of shock was closely related to age, length of time between injury and hospitalization, and burn area. The shock incidence of children under 7 years old or elderly more than 60 years old was obviously higher than other age groups, and there was positive relationship between burn area and shock incidence. Moreover, the shock incidence of the patients hospitalized later than 4 to 12 hours after burn shock was also markedly higher than those hospitalized earlier (P < 0.01). In addition, the incidence of sepsis, alimentary tract hemorrhage, acute renal failure, pulmonary failure, and cardiac failure in patients with shock was obviously higher than those without shock (P < 0.01). CONCLUSION: For the children and aged people, special attention should be paid in the prevention and resuscitation of burn shock. Early fluid resuscitation is vital for the prevention of organ complication, and it is beneficial to promote wound healing. PMID- 17283878 TI - [The changes in the HIF-1alpha expression during hypovolemic shock and its role in the pathogenesis of vascular hyporeactivity]. AB - OBJECTIVE: To investigate the changes in the expression of HIF-1alpha in rat superior mesenteric artery (SMA) tissue after hypovolemic shock (HS), and its relationship with the pathogenesis of vascular hyporeactivity. METHODS: One hundred and twelve SD rats were used in the study, and they were randomly divided into HS group (n = 56) and treatment group (n = 56, with intraperitoneal injection of 9 microg/kg oligomycin 4 h before the experiment). Arterial blood of the rats in each group were harvested at 0.0, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0 post injury hour (PIH), respectively,with 8 rats at each time-points. Then the rats were sacrificed and superior mesenteric arteries (SMA) were harvested. Other 8 rats without any treatment served as normal controls. The changes in mRNA expression of HIF-1alpha, inducible nitric oxide synthase (iNOS) and hemeoxygenase 1 (HO-1) were determined with RT-PCR. The contraction of vascular ring of SMA to gradient concentration of norepinephrine (NE) was measured with ex vitro vascular ring tension determination method. The plasma content of carbon monoxide and nitric oxide were measured with sodium dithionite reduction method and nitrate reductase method, respectively. RESULTS: Compared with normal controls, Vascular reactivity of SMA in HS group increased compensatorily during early stage of HS (0.0 -1.0 h), and peaked at 0.5 h. The pD2 ( - log[ NE] ) of NE decreased, but the maximal contraction (Emax) was above the normal level during 0.0 - 1.0 PIH (P < 0.01). During the middle and late shock stage, the vascular reactivity decreased gradually. The Emax decreased, pD2 increased, and the Emax was below the normal level at 4.0 PIH (P < 0.01). The increase of vascular reactivity in treatment group was partially inhibited during early stage after injury (P < 0.01). The Emax was (2.01 +/- 0. 22) g/mg at 0.5 PIH, which was obviously lower than that in HS group [(2.96 +/- 0.18) g/mg , P < 0.05]. In decompensated period of HS, the vascular reactivity was improved mildly, which exhibited obvious difference compared with that in HS group at 4.0 and 6.0 PIH (P < 0.05 or P < 0.01). HIF-1alpha mRNA expression in HS group exhibited a time dependent increase following HS, and peaked at 4.0 PIH (P < 0.01), and the iNOS and HO-1 mRNA expression were also gradually increased, reaching the peak value at 2.0 and 4.0 PIH, respectively (P < 0.01). The plasma content of CO and NO in whole blood were gradually increased following the shock process when compared with those in normal control group, while the CO content in whole blood in treatment group maintained normal, and the plasma content of NO was obviously decreased compared with that in control group. CONCLUSION: HS can elicit a dual phase change in vascular reactivity as previously described. HIF-1alpha plays an important role in the occurrence of vascular hyporeactivity following HS. PMID- 17283879 TI - [The involvement of ERK pathway in the cellular phenotype conversion in human mesenchymal stem cells cocultured with human sweat gland cells]. AB - OBJECTIVE: To study the cellular phenotype conversion of human mesenchymal stem cells (MSCs) cocultured with human sweat gland cells (SGCs) and the contribution of extracellular signal-regulated kinase (ERK) pathway in the process. METHODS: MSC and SGC were isolated, amplified , and identified with two-step immunohistochemistry method. The primary SGCs were heat-shocked at 47 degrees C. Then the supernatants were collected immediately and 24hr later. The 3rd passage of MSCs were divided into control, SGC supernatant (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant), SGC supernatant + EGF (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant and 50 microg/L EGF), and SGC supernatant + PD98059 (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant and 10 micromol/L PD98059) groups. The positive expression of CK7and CEA in MSCs were detected on the 7th post-stimulation day (PSD) by flow cytometry. The expression of ERK and phosphorylated ERK were determined with Western blotting. RESULTS: The positive expression rate of CK7 and CEA was (5.76 +/-0.10)%, (2.01 +/- 0.09)% in SGC supernatant group; (7.31 +/- 0.21)% and (7.27 +/- 0.12)% in SGC supernatant + EGF group; and (1.63 +/- 0.11)%, (1.54 +/- 0.07)% in SGC supernatant + PD98059 group; they were all obviously higher than that in control group (P < 0.01). Moreover, ERK expression was observed in all groups. The expression of pERK in SGC supernatant + EGF group was higher than that in SGC supernatant group, but almost no expression of pERK was found in the SGC supernatant + PD98059 and control groups. CONCLUSION: Indirect coculture of MSCs with SGCs can induce the phenotype conversion of MSCs through ERK pathway. PMID- 17283880 TI - [Activation of nuclear factor-kappaB signaling pathway in rat gastric mucosa during stress ulceration]. AB - OBJECTIVE: To investigate the time course of nuclear factor-kappaB (NF-kappaB) activation in the process of stress ulcer formation. METHODS: Model of stress ulcer was reproduced by subjecting male Sprague-Dawley rats to water-immersion restraint (WIR) stress. At indicated time after the beginning of WIR stress, animals were sacrificed and cytoplasmic and nuclear protein and total RNA were prepared from gastric corpus mucosal tissues. DNA-binding activity of NF-KB was assessed as an index of NF-kappaB activation with electrophoretic mobility shift assay. Degradation of IkappaBalpha and IkappaBbeta, the inhibitory proteins of NF kappaB, was analyzed by Western blot analysis. Expression of NF-kappaB dependent genes including tumor necrosis factor-alpha (TNF-alpha) , interleukin-1beta (IL 1beta), cytokine-inducible neutrophil chemoattractant-1 ( CINC-1), intercellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthase (iNOS) was detected with Northern blot analysis. RESULTS: WIR stress induced a rapid biphasic activation of gastric mucosal NF-kappaB within 15 min of the beginning of stress, peaking at 45 min and 360 min. Compared with baseline, NF-kappaB activation by stress was increased (10.6 +/- 1.3) and (8.9 +/- 1.2) fold at 45 min and 360 min, respectively (P < 0.01). Antibody supershift assays revealed that p50/p65 heterodimer was the major active component of mucosal NF-kappaB. Western blot analysis showed that degradation of IkappaBalpha and IkappaBbeta occurred at first and second wave of NF-kappaB activation. Corresponding with the rapid and persistent activation of NF-kappaB, the levels of TNF-alpha, IL-1beta, CINC-1 and ICAM-1 mRNA in gastric mucosa were markedly increased 15 to 30 min after stress, respectively. Up-regulation of iNOS mRNAs was observed 30 to 90 min after stress, and the expression of all of these genes was increased consistently until the end of stress. CONCLUSION: NF-kappaB activation is an early event and may play an important role in proinflammatory gene over-expression in rat gastric mucosa during WIR stress. PMID- 17283881 TI - [Purification, identification and oriented differentiation of endothelial progenitor cells from human umbilical cord blood]. AB - OBJECTIVE: To explore the endothelial progenitor cell markers and biological characteristics of human CD133 umbilical cord blood cells( EPC). METHODS: CD133+ cells were enriched from human umbilical cord blood by immunomagnetic sorting, and cultured with EGM-2MV medium containing epidermal growth factor, vascular endothelial growth factor and fibroblast growth factor 2. The percentage of CD133+ cells in cord blood monocytes, the growth curve and growth characteristics of primary EPCs were measured by flow cytometry and immunochemistry method. Weibel-Palade body was observed with transmission electron microscope. The mixture of EPCs and human stomach cancer cell line GC7901 were injected into athymic mice to observe the tumor growth and vascularization. RESULTS: The percentage of CD133+ cells in cord blood monocytes was 0.91%, and after sorting, the percentage of CD133+ cells was raised to 85.52%. The cultured cells showed a typical spindle-shaped morphology in 3 post-culture days (PCD) and areas of clusters of cobblestone-like cells in 10 PCD. The number of EPC increased from 7 PCD on, peaked on 17 PCD. Obvious amplification and clone-like growth on 7 PCD were observed by light microscope. Typical Weibel-Palade body was observed in the cells under transmission electron microscope. Tumor forming experiment in athymic mice showed that the tumor size of EPC group was larger than that of control with smaller necrosis area and more and larger blood vessels. Immuno-fluorescent staining showed many human vWF antigen-positive endothelial cells being involved in the tumor vascularization. CONCLUSION: Immunomagnetic sorting can efficiently enrich EPC from human umbilical cord blood. Our data support that the EPC may contribute to angiogenesis, speed up vascularization of ischemic tissue. PMID- 17283882 TI - [The effects of aloe extract on nitric oxide and endothelin levels in deep partial thickness burn wound tissue in rat]. AB - OBJECTIVE: To investigate the effects of polysaccharide extracted from Aloe barbadensis and Aloe barbedensis containing gel on tissue water contents, nitric oxide (NO) and endothelin (ET) levels in wounds of burned rats. METHODS: Four areas of deep-partial thickness burn wounds with 3 cm in diameter were made on each back of 42 male Wistar rats. Single layer gauze impregnated either with 5% (W/W) aloe raw polysaccharide, 10% (W/W) aloe gel, 1% (W/W) sulfadiazine pyridine silver cream (SD-Ag), or normal saline was respectively applied on different wounds. According to different medications, the wounds were divided into aloe raw polysaccharide group, aloe gel group, SD-Ag group and normal saline group. Six rats in each group were sacrificed at 4, 12, 24, 48 post-scald hour (PSH) and on 7, 14, 21 post-scald day (PSD), and the full-thickness skin of wound was harvested for the determination of wound tissues water contents, NO and ET levels, and for calculation of NO/ET ratio. Another 6 normal rats served as normal controls. RESULTS: The water content in the wound tissue in aloe raw polysaccharide group at 12, 24 and 48 PSH [(73.4 +/- 3.8)%, (76.6+/-3.0)%, (70.6+/-3.8)%] and aloe gel group [(74.5+/-2.6)%, (77.1+/-3.6)%, (71.2 +/- 3.1)%] was obviously lower than those in SD-Ag group [(80.1 +/- 4.1)%, (80.5 +/-3.9)%, (76.1 +/-3.8)%, P <0.05]. During 7-21 PSD, all of them returned to the normal level except that in SD-Ag group, as it was still higher than that in normal controls (P < 0.05). The NO content in wound tissue in each group reached the peak at 12 PSH, decreased thereafter, but it was still obviously higher than that of normal controls on 21 PSD (P < 0.05). The ET content in wound tissue of each group reached the peak on 7 or 14 PSD, decreased thereafter, but it was still evidently higher than that in normal controls on 7 or 14 PSD (P < 0.05). The NO content in wound tissue in aloe raw polysaccharide and aloe gel group were markedly lower than those in SD-Ag and normal saline groups at 12 and 24 PSH ( P < 0.05). The NO/ET ratio in each group reached the peak at 12 PSH, decreased thereafter, and it returned to normal value on 14 PSD. On 7 PSD, the NO/ET ratio in aloe gel, SD-Ag and normal saline groups were still significantly higher than that in normal controls, except that returned to normal value in aloe raw polysaccharide group. CONCLUSION: Both aloe raw polysaccharide and aloe gel can decrease wound tissue NO release, optimize NO/ET ratio, lighten vascular inflammatory reaction, and lessen permeability and edema. PMID- 17283883 TI - [The role of nuclear factor-kappaB in the burn serum-induced expression of intercellular adhesion molecules-1 in endothelial cells]. AB - OBJECTIVE: To explore the role of nuclear factor-kappaB (NF-kappaB) in the burn serum induced expression of intercellular adhesion molecules-1 (ICAM-1) in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and divided into control (with normal serum stimulation), burn serum (B, with burn serum stimulation) and PDTC (with burn serum and PDTC stimulation) groups. The NF-kappaB activity in endothelial cells was determined with electrophoretic mobility shift assay (EMSA) at 0.5, 1.0, 2.0, 4.0 post stimulation hour (PSH). The expression of ICAM-1 at 3.0, 6.0, 12. 0, 24.0 PSH was detected by flow cytometry. RESULTS: The NF-kappaB activity in endothelial cells in burn serum group and PDTC group were markedly higher than that in control group (P <0.01), and it reached the peak at 1.0 PSH [(21.03 +/- 4.87), (7.44 +/- 0.60) x 10(4) A], respectively, then gradually decreased. But it was obviously lower in PDTC group than that in burn serum group ( P <0. 01 ). The expression of ICAM-1 was gradually increased in both burn serum group and PDTC group, reaching the peak level at 12.0 PSH [(327 +/- 37), (142 +/- 31) mean fluorescence intensity], respectively, which were significantly higher than that in control group (P <0.01). But it was evidently lower in PDTC group than that in burn serum group at 12.0 and 24.0 PSH (P <0.01). CONCLUSION: Burn serum can initiate the synthesis and release of adhesion molecules in endothelial cells through activation of NF-kappaB, indicating that NF-kappaB plays an important role in the process of burn serum induced endothelial secretion of adhesion molecules. PMID- 17283884 TI - [Study on the antisense oligonucleotide against peroxisome proliferator-activated receptors promoting TNF-alpha mediated apoptosis of HaCat cells]. AB - OBJECTIVE: To investigate the influence of antisense phosphorothioate oligonucleotides on peroxisome proliferator-activated receptors (PPARbeta) in the TNF-alpha mediated apoptosis of HaCat cells. METHODS: HaCat cells were resuscitated and randomly divided into normal control (without transfection), sham (merely with liposome transfection), scrODN (with transfection of 4 micromol/L PPARbeta scrODN), asODN (with transfection of 4 micromol/L PPARbeta asODN), TNF-alpha with transfection of 10 micromol/L TNF-alpha), scrODN + TNF alpha with 10 micromol/L TNF-alpha stimulation after transfection of 4 micromol/L PPARbeta scrODN), asODN + TNF-alpha with 10 micromol/L TNF-alpha stimulation after transfection of 4 micromol/L PPARbeta asODN) groups. The mRNA and protein levels of PPARbeta were determined with RT-PCR and Western blotting, respectively. The changes in cell morphology were observed with Hoechst 33258 fluorescent staining to quantitate apoptotic rate of nuclei. The effect of PPARbeta asODN on HaCat cell viability was assayed with MTT method. Activation of caspase-3 was evaluated with caspase colorimetric analysis kit. RESULTS: The mRNA and protein expression of PPARbeta in normal control, sham, scrODN groups were similar, but it decreased obviously in asODN group. The nuclear apoptotic rate in normal control, scrODN and asODN groups were rather low, and the caspase-3 activity in these groups was also low. After 24 hours of culture, the nuclear apoptotic rate in TNF-alpha and scrODN + TNF-alpha groups were (33.1 +/- 2.7)% and (32.9 +/- 3.0)%, respectively, while that in asODN + TNF-alpha group was obviously increased (58.8 +/- 4.6)%, with the caspase-3 activity significantly higher, but the number of live cells markedly lower than that in the former 2 groups (P < 0.05). CONCLUSION: PPARbeta expression can promote the apoptosis of HaCat cells mediated by TNF-alpha. PMID- 17283885 TI - Development of hyperfibrinogenemia in spontaneously hypertensive and hyperlipidemic rats: a potentially useful animal model as a complication of hypertension and hyperlipidemia. AB - According to current concepts, hypertension and hyperlipidemia cause vascular damage that leads to a hypercoagulative state. In this study, we investigated whether spontaneously hypertensive and hyperlipidemic rats (SHHR) can be a useful experimental model for complications in combined hypertension and hyperlipidemia, by comparing coagulative and fibrinolytic activities in SHHR with those in spontaneously hypertensive rats (SHR) and spontaneously hyperlipidemic rats (HLR). We measured coagulation and fibrinolysis markers in plasma and levels of fibrinogen and prothrombin mRNA in livers of eight-month-old male Wistar Kyoto rats (WKY), Sprague-Dawley rats (SD), SHR, HLR and SHHR. The plasma levels of fibrinogen in SHR, HLR and SHHR were significantly higher than those in WKY and SD, and were highest in SHHR. Higher plasma levels of antithrombin III and plasminogen were detected in increasing order in SHR, HLR and SHHR as compared to those in WKY and SD. Hepatic mRNA expressions of fibrinogen chains and prothrombin were enhanced in SHR, HLR and SHHR, resulting in increased plasma fibrinogen levels in SHHR. These results suggest that hypertension and hyperlipidemia can each cause hypercoagulation, with hyperlipidemia being a stronger factor than hypertension. Since a greater hypercoagulative state is a complication of combined hypertension and hyperlipidemia, the SHHR model is a good system for studying the early stage of atherosclerosis ensuing from hyperfibrinogenemia. PMID- 17283886 TI - Severe insulin resistance and moderate glomerulosclerosis in a minipig model induced by high-fat/ high-sucrose/ high-cholesterol diet. AB - To develop a minipig model of type 2 diabetes that simulates the common manifestations of the metabolic abnormalities and resembles the kidney pathology of type 2 diabetes in the human population, male Chinese Bama minipigs were divided into 2 groups (5 in each) and fed with a control diet (CD) or high-fat/ high-sucrose/ high-cholesterol diet (HFSCD) for 5 months. The biochemical parameters of blood and urine, and the oral glucose tolerance test were monitored after the feeding program. The insulin resistance was estimated by the HOMA-IR index and the glucose elimination constant (K(G)), and beta-cell function by the HOMA-beta index and the acute insulin response (AIR). Glomerulosclerosis index (GSI) was semi-quantitated by the degree of glomerular lesions in kidney sections stained with Masson trichrome. Extracellular matrix deposition in the kidney was examined by the protein expression of type IV collagen, connective tissue growth factor (CTGF) and matrix metalloproteinases 2 (MMP-2) using immunohistochemistry. Feeding HFSCD to minipigs markedly caused hyperglycaemia, hyperinsulinaemia and dyslipidaemia. HOMA-IR was significantly increased while HOMA-beta, AIR and K(G) were obviously decreased in the HFSCD group compared with control group. Microalbuminuria, glucosuria and moderate glomerulosclerosis were exhibited in HFSCD-fed minipigs. The expression of type IV collagen and CTGF was elevated whereas that of MMP-2 was reduced in the kidneys of HFSCD group compared with the CD group. We concluded that feeding HFSCD to Chinese Bama minipigs for 5 months can induce humanoid type 2 diabetes and early-stage diabetic nephropathy, and accelerate extracellular matrix deposition and glomerulosclerosis. PMID- 17283887 TI - Age-dependent changes in iron deposition in the gerbil hippocampus. AB - In this study, we focused on age-dependent changes in intracellular iron deposition in the gerbil hippocampus. At 1 month of age (PM 1), iron reactivity was weak in the gerbil hippocampus. At this time, cells in the polymorphic layer of the dentate gyrus showed weak iron reactivity. At PM 3, iron reactivity in cells had not changed significantly. Thereafter, iron reactivity in the CA1-3 regions and in the dentate gyrus increased with time until PM 18. At PM 24, iron reactivity in all the subfields was similar to that at PM 18. In animals aged PM 18-24, iron positive cells had various shapes, and had processes which contained iron. These results suggest that the increase of iron deposition may be associated with normal aging and that the iron deposition in the aged hippocampus is different according to hippocampal subfields. PMID- 17283888 TI - Fertility of spermatozoa cryopreserved with 2% acetamide or glycerol through artificial insemination in the Japanese white rabbit. AB - The rabbit is considered to be a valuable laboratory animal. We compared 2% acetamide and glycerol as cryoprotectants in egg-yolk diluent for ejaculated Japanese white rabbit spermatozoa to improve sperm cryopreservation methods. Fertility through artificial insemination, forward progressive motility and plasma membrane integrity of the post-thaw spermatozoa were examined. The rates of forward progressive motility and plasma membrane integrity of the spermatozoa frozen with acetamide (27.1 +/- 8.3% and 24.5 +/- 6.5%) were significantly (P < 0.05) higher than those of the spermatozoa frozen with glycerol (16.3 +/- 10.9% and 14.3 +/- 7.6%). Though there was no significant difference in the kindling rates, the litter size of females inseminated with spermatozoa frozen with acetamide (6.0 +/- 1.1) were significantly (P < 0.05) higher than those of spermatozoa frozen with glycerol (3.0 +/- 0.4). The results indicate that 2% acetamide has a higher cryoprotective effect than 2% glycerol for sperm cryopreservation in the Japanese white rabbit. PMID- 17283889 TI - Effects of xylene and formaldehyde inhalations on oxidative stress in adult and developing rats livers. AB - In this study, it was aimed to demonstrate the possible oxidative stress caused by exposure of xylene and formaldehyde (HCHO) on liver tissue, and on body and liver weights in adult as well as developing rats. The rats (96 female Sprague Dawley) were randomly divided into four groups: embryonic day 1 (Group 1), 1-day old infantile rats (Group 2), 4-week-old rats (Group 3) and adult rats (Group 4). The animals were exposed to gases of technical xylene (300 ppm), HCHO (6 ppm) or technical xylene + HCHO (150 ppm + 3 ppm), 8 hours per day for 6 weeks. Superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) and malondialdehyde (MDA) levels were evaluated. In addition, body and liver weights were determinated. Compared to the control animals, body and liver weights were decreased in the embryonic day 1 group (P < 0.001, P < 0.01, respectively) and the 1-day-old infantile group (P < 0.001). Liver weight was increased in the 4-week-old group (P < 0.01). SOD activities were decreased in the 4-week-old rats exposed to HCHO (P < 0.01). CAT activities increased in the embryonic day 1 group (P < 0.05). GSH levels were decreased in the 1-day-old infantile group (P < 0.01), and MDA levels was increased in the embryonic day 1 group (P < 0.05) as compared with the respective control groups. As to GSH and MDA levels in adult and 4-week-old animals, no statistically significant differences were observed (P > 0.05). The present study indicates that exposures to xylene, HCHO and a mixture of them are toxic to liver tissue, and developing female rats are especially more adversely affected. Furthermore, the results of this study show that adult female rats could better tolerate the adverse effects of these toxic gases. PMID- 17283890 TI - Carbonic anhydorase isoenzyme I (CA-I) concentration in feces and urine as a temporary marker of occult blood in beagle dogs. AB - This study was undertaken to investigate whether the concentration of carbonic anhydorase isoenzyme I (CA-I) in canine feces and urine is useful as a temporary marker of occult blood. Concentrations of CA-I were measured by enzyme-linked immunosorbent assay (ELISA). Fecal CA-I concentrations in 113 healthy beagle dogs (50 male and 63 female) of various ages ranged from 4.3 to 16.7 ng/g feces (mean; 7.0 +/- 2.9 ng/g feces). One milliliter of blood from 3 healthy beagle dogs was found to contain 1,047, 1,062 and 1,150 microg CA-I. The fecal CA-I concentrations of dogs receiving intragastric infusions of autologous blood (10 ml) were very low. However, the fecal CA-I concentrations of dogs receiving infusion of autologous blood (5 ml) into the ascending colon were very high. Detection of fecal CA-I would be useful for identifying dogs with hemorrhaging of the large intestine. Of 55 urinary samples collected from healthy beagle dogs by catheter, chemical tests for occult blood were negative in 44, but CA-I concentrations ranged from 1.8 to 12.6 ng/ml (mean; 6.9 +/- 5.4 ng/ml) by ELISA. The CA-I concentrations of the other 11 samples, which tested positive for occult blood on chemical testing, ranged from 41.2 to 525.0 ng/ml by ELISA. Although CA I is not a specific marker of erythrocytes, CA-I may be used to detect occult blood in canine feces and urine until a specific immunological test kit using antibody for Hb is developed. PMID- 17283891 TI - A novel set of microsatellite marker loci linkage-mapped in the house musk shrew, Suncus murinus. AB - Ten microsatellite DNA loci developed for the white-toothed shrew (Crocidura russula) were tested for PCR amplification and for utility in linkage studies in the house musk shrew, Suncus murinus. Four primer pairs successfully yielded PCR amplicons and showed polymorphism between two mutant strains, BAN-kc,oeb and WZ. Cloning and sequencing of the PCR amplicons of all the four loci confirmed the presence of microsatellite sequences. Alleles segregating in an F2 resource population constructed from the two strains ranged between two and five. Linkage analysis of the four loci together with 18 other polymorphic markers and three mutant loci resulted in five linkage groups containing three newly mapped microsatellite loci. This study reports the first microsatellite markers being registered in this species. PMID- 17283892 TI - Correlation among clinicopathological parameters of myocardial damage in rats treated with isoproterenol. AB - The correlation among clinicopathological parameters of myocardial damage was investigated in rats administered a single subcutaneous dose of isoproterenol at 0 (saline), 0.04, 0.4 and 4 mg/kg. Total lactate dehydrogenase (LDH), creatine kinase (CK), and their isoenzymes (LDH-1, LDH-2 and CK-MB), as well as troponin I and tropinin T, were measured 4 h after the administration of the drug. Troponin I was determined by a chemiluminescence method using Bayer Centaur and DPC Immulyze, as well as by ELISA. Troponin T was assayed semi-quantitatively using Trop T Sensitive. A high correlation was found among LDH isoenzymes, troponin I (Centaur) and troponin T. The present result provides a baseline for interpreting changes in the different parameters of myocardial damage assayed by different methods in toxicity studies. PMID- 17283893 TI - A new molecular genetic diagnosis of the Btk(xid) mice. AB - A new method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was developed for genetic typing of a point mutation of the Bruton's tyrosine kinase (Btk) gene in CBA/N mice bearing an X linked recessive immunodeficiency (xid). Since restriction site useful for RFLP analysis does not exist in the spontaneous mutant Btk(xid) locus, an artificial restriction site was introduced by PCR amplification with a modified primer. The five genotypes of the Btk locus (Btk(xid)/ Btk(xid), Btk(xid) /Btk+ and Btk+/Btk+ females and Btk(xid)/Btk(null) and Btk+/Btk(null) males) could be distinguished by three patterns clearly and easily. This PCR-RFLP analytic method will be useful as a tool in the production of congenic mice and mice with multiple immunodeficient genes. PMID- 17283895 TI - A universal vaccine against influenza. PMID- 17283894 TI - Microbial flora in the ears of healthy experimental beagles. AB - There are studies of the microbial flora of the normal canine ear canal, but it is difficult to compare their results because the parts of the ear examined are not described, and various breeds of dogs were used. Therefore, we used only beagles to study the normal microbial flora in three parts of the ear: the pinna, the anthelix, and the vertical ear canal. The rates of bacterial isolation from the three parts were 91.8%, 70.5% and 48.8%, respectively. The corresponding rates of isolating yeasts was 48.8%, 81.4%, and 83.7%, respectively. These results show that the physiologic factors of the three parts of the ear from which the samples were obtained must be radically different. PMID- 17283896 TI - [Avian influenza: the ballad of influenza or the art of the fugue]. PMID- 17283897 TI - [Influenza: an example of interdisciplinary analysis of risks]. PMID- 17283898 TI - [Influenza: an old problem from a new perspective]. PMID- 17283899 TI - [Human influenza A (H5N1) -- pathogenic clues]. PMID- 17283901 TI - Serine protease inhibitors: pathological and therapeutic insights. PMID- 17283900 TI - [Role of caveolin in angiogenesis and vasculogenesis processes: therapeutic implications in ischemic diseases and cancerology]. PMID- 17283902 TI - [Physiopathology of heart failure: experimental model and therapeutic effects]. AB - Studies have shown the importance of heart rate variability alterations as a marker of neurohumoral dysregulation and haemodynamic derangements in experimental heart failure. Other studies have also revealed the importance of enhanced sympathetic nerve traffic and chemoreflex dysregulation in patients with pulmonary hypertension. Furthermore, the lack of favorable effects of beta mimetic agents on long term survival in heart failure patients may implicate an absence of sympathoinhibition, possibly related to a sensitization of the peripheral chemoreceptors. Sympathetic hyperactivity is however reduced by cardiac resynchronisation therapy. Last, a comparison of sympathetic nerve traffic during normoxia and hyperoxia in heart transplant recipients, essential hypertensive patients and control subjects has revealed that transplantation does not normalize peripheral chemoreflex hyperactivity and hypersensitivity. This mechanism contributes to blood pressure elevation and exercise hyperpnea in cardiac transplant recipients. PMID- 17283903 TI - [Trypanolytic factor of human serum]. AB - African trypanosomes (prototype : Trypanosoma brucei) are protozoan flagellates that infect a wide range of different mammals. In humans these parasites have to counteract innate immunity because, unlike other mammals, human serum possesses efficient trypanolytic activity. Resistance to this activity has arisen in two T. brucei subspecies, termed T. b. rhodesiense and T. b. gambiense, allowing them to infect humans where they cause sleeping sickness in East and West Africa respectively. The study of the mechanism by which T. b. rhodesiense escapes lysis by human serum led to the identification of the trypanolytic factor, which turned out to be an ionic pore-forming apolipoprotein associated with some HDL particles. PMID- 17283904 TI - [Molecular characteristics of dendritic cells from newborn infants]. AB - The immaturity of the immune system represents a significant challenge for the induction of protective immune responses in early life. In the context of this work, we evaluated the function of human neonatal dendritic cells. We observed that their capacity to produce interleukin-12 and interferon-beta, two cytokines involved in anti-infectious responses, was strongly impaired. These results led us to analyze the signaling pathways and the regulatory mechanisms responsible for the control of these genes in both adult and neonatal dendritic cells. PMID- 17283906 TI - [Nephropathy caused by Chinese plants and aristolochic acids: from clinical observation to experimental model]. AB - In 1992, a new type of progressive renal fibrosis was reported in patients after the intake of weight-reducing pills containing a Chinese herb (Aristolochia fangchi) rich of nephrotoxic and carcinogenic aristolochic acids (AA). Up to now, Chinese herb nephropathy (CHN), also called aristolochic acid nephropathy (AAN), has been observed in more than 100 patients in Belgium, but also in numerous patients all around the world. The main histological characteristics of CHN are tubular atrophy and interstitial fibrosis leading to severe renal functional impairment and end-stage renal failure. Urothelial carcinomas were also found in about 50% CHN patients suffering from end-stage renal failure. Experimentally, the main features of CHN were successfully reproduced after 35 days of daily AA injections to rats. Starting from this model, we demonstrated that other potential nephrotoxic substances (dexfenfluramine, diuretics) also contained in the weight-reducing pills, did not enhance the renal toxicity of AA. Interestingly, the inhibition of renin angiotensin system did not prevent the development of renal lesions, suggesting that, in contrast with other animal models, physiopathological mechanisms leading to renal fibrosis might be largely independent of angiotensin II. From clinical observations to experimental studies, we currently increased our knowledge in the understanding of pathophysiological mechanisms of nephropathies of toxic origin. Botanicals which are known or suspected to contain AA are still sold on Web sites or over-the counter markets. It is not surprising then to find new AAN cases reported in the medical literature. Therefore, further studies are needed to elucidate pathways of AA-related nephrotoxicity and carcinogenicity in order to develop therapeutic strategies. PMID- 17283905 TI - [Roles of serine proteases and matrix metalloproteinases in tumor invasion and angiogenesis]. AB - The remodelling of extracellular matrix and angiogenesis represent two essential processes for tumor growth and metastatic dissemination. These phenomena imply many interactions between tumor cells and host cells via action of various proteases including metalloproteinases (MMPs) whose activity is controlled by TIMPs and serine proteases (tissue type Plasminogen Activator (tPA), urokinase type Plasminogen Activator (uPA) and plasmin) inhibited in particular by PAI-1 (Plasminogen Activator Inhibitor- 1). Evolution of tumors depends on the joint action of these enzymes, as well as precise balance between these proteases and their physiological inhibitors. Proteases regulate the fate and activity of many proteins by controlling appropriate intra- or extracellular localization; shedding from cell surfaces ; activation or inactivation of proteases and other enzymes, cytokines, hormones or growth factors and exposure of cryptic neoproteins. Hence, proteases initiate, modulate and terminate a wide range of important cellular functions by processing bioactive molecules an thereby control essential biological processes, such as DNA replication, cell-cycle progression, cell proliferation, differentiation and migration, morphogenesis and tissue remodelling, neuronal outgrowth, haemostasis, wound healing, immunity, angiogenesis and apoptosis. Work completed has for objective to elucidate the specific part played by serine proteases and MMPS produced by the host cells in the processes of tumor growth and angiogenesis. By using an original model of transplantation of malignant murine keratinocytes (PDVA cell line) into deficient mice (-/-) and wild type mice (+/+), we showed the essential proteolytic role of PAI-1 produced by host cells in the tumor progression and angiogenesis. This mechanism of PAI-1 action was confirmed by using the model in vitro aorta rings. By using deficient mice for one or two MMPs combined (MMP-2, MMP-3, MMP-9, MMP 11, MMP-2&9, MMP3&9), we demonstrated that only the combined deficiency of MMP-2 and -9 showed an absence of tumor invasion and angiogenesis. These data suggest the existence of compensatory mechanisms of a MMP by another MMP or another proteolytic way. These phenomena of redundancy are to be known and detailed to elaborate in a near future, the development of specific inhibitors of MMPS. PMID- 17283907 TI - The case for interdisciplinary collaboration. PMID- 17283908 TI - My journey to an integrated clinical practice. PMID- 17283909 TI - Holistic nursing model for hospital-based integrative care. PMID- 17283910 TI - Activities research at the 2006 conference. PMID- 17283911 TI - Creating inroads for integrative health care. PMID- 17283912 TI - Show us the data! NDNQI helps nurses link their care to quality. PMID- 17283913 TI - Centered on the workforce... conflict and the nursing workforce. PMID- 17283914 TI - Sparky speaks! North Carolina nurse spreads fire prevention message to young, old and everyone in between. PMID- 17283915 TI - ANA call to action: get your flu vaccine! PMID- 17283916 TI - ANCC announces introduction of new specialty exams. PMID- 17283917 TI - The impact of payer-specific hospital case mix on hospital costs and revenues for third-party patients. AB - Competition among hospitals and managed care have forced hospital industry to be more efficient. With higher degrees of hospital competition and managed care penetration, hospitals have argued that the rate of increase in hospital cost is greater than the rate of increase in hospital revenue. By developing a payer specific case mix index (CMI) for third-party patients, this paper examined the effect of hospital case mix on hospital cost and revenue for third-party patients in California using the hospital financial and utilization data covering 1986 1998. This study found that the coefficients for CMIs in the third-party hospital revenue model were greater than those in the hospital cost model until 1995. Since 1995, however, the coefficients for CMIs in the third-party hospital revenue model have been less than those in hospital cost models. Over time, the differences in coefficients for CMIs in hospital revenue and cost models for third-party patients have become smaller and smaller although those differences are statistically insignificant. PMID- 17283918 TI - Factors affecting inpatient satisfaction: structural equation modeling. AB - OBJECTIVE: Our study aimed to identify factors affecting patient satisfaction. DATA: The study was conducted at a training hospital in Turkey. The final sample consisted of 302 inpatients. In this study, patient satisfaction was examined using a survey questionnaire with 22 questions collected under five dimensions. METHOD: Factor analysis was used to group 22 questions measuring patients' satisfaction questions into certain dimensions. Then, structural equation model (SEM) was performed to determine the influence of patient characteristics on patient satisfaction. RESULTS: Our analysis showed the questionnaire has an appropriate reliability and validity. The structural equation model (SEM) was used to determine those factors which could affect patient satisfaction. The results of SEM analysis showed that 15% of the total variance in patients' satisfaction was explained by the model. The SEM analysis found that variables of education and type of clinic (surgical vs. non-surgical) were significant on patient satisfaction. Persons with a higher level of education were less satisfied when compared to those with a lower level of education. Surgical patients are more satisfied with the care they received when compared to non surgical patients. CONCLUSION: The education level of patients and the type of clinics had a significant influence on patient satisfaction. PMID- 17283920 TI - Electronic medical records for a rural family practice: a case study in systems development. AB - In this paper, we describe the planning, development, and overall impact of Electronic Medical Records (EMRs) on Dryden Family Medicine (DFM), a rural family practice in Dryden, New York. The EMR system was installed in July, 2003, and the full conversion to the new system was accomplished in three phases. Significant efficiency gains were achieved in billing, prescription ordering, and other routine processes. Protocols were developed to enhance quality management, preventive medicine, and disease management. Job responsibilities changed and expanded for all members of the practice and coding issues became paramount. Practice revenue increased by about 20 percent and average "case-mix" increased by 10 percent in the second year following the implementation of EMRs due to improved billing documentation. We focus on the implementation process, the lessons learned, the obstacles encountered, and the successes achieved by one rural family practice. PMID- 17283919 TI - Analysis of yearly variations in drug expenditure for one patient using data warehouse in a hospital. AB - Medical expense has grown rapidly in Japan. It could be caused by the increase of the patient number and the increase of medical expense per patient. We studied the latter factor on drug expenditure from 1996 to 2002 using the prescription data stored in the data warehouse of one hospital. We found that the drug expenditure per patient had increased 1.32 times. The mean number of prescriptions per patient increased 1.23 times and the mean expenditure of one medicine increased 1.08 times. These results demonstrated that drug expenditure for one patient had gradually increased. This was caused by both the rise in the number of medicines taken by one patient and the rise in the prices of medicines. The data warehouse in the hospital was useful for the analysis of the trends in medical expenditure for one patient. PMID- 17283921 TI - Regional health information organizations: a vehicle for transforming health care delivery? AB - Information technology (IT) has the potential to be a significant enabler in transforming the health care delivery system. New types of organizations are needed to guide the change. Regional Health Information Organizations (RHIOs) hold promise as agents for transformation. This essay discusses the results from a case study on how RHIOs are advancing IT adoption in the health care community. Results indicate that the RHIO model is early in its evolution. To be a catalyst of change, the RHIO must overcome privacy barriers, actively engage purchasers of care, and create compelling incentives for clinicians to adopt the RHIOs' services. PMID- 17283923 TI - Backpropagation artificial neural network detects changes in electro encephalogram power spectra of syncopic patients. AB - This paper presents an effective application of backpropagation artificial neural network (ANN) in differentiating electroencephalogram (EEG) power spectra of syncopic and normal subjects. Digitized 8-channel EEG data were recorded with standard electrodes placement and amplifier settings from five confirmed syncopic and five normal subjects. The preprocessed EEG signals were fragmented in two second artifact free epochs for calculation and analysis of changes due to syncope. The results revealed significant increase in percentage delta and alpha (p < 0.5 or better) with significant reduction in percentage theta activity (p < 0.05). The backpropagation ANN used for classification contains 60 nodes in input layer, weighted from power spectrum data from 0 to 30 Hz, 18 nodes in hidden layer and an output node. The ANN was found effective in differentiating the EEG power spectra from syncopic EEG power spectra and the normal EEG power spectra with an accuracy of 88.87% (85.75% for syncopic and 92% for normal). PMID- 17283922 TI - Design and development of a mental health assessment and intervention system. AB - Mental health disorders are the leading cause of disability and functional impairment in the United States (1 in 5). The negative effect of mental health disorders is felt both in the personal and public lives of the affected individuals, particularly in the workplace where it adversely impacts productivity. Only a small fraction of the affected people in the work force seeks help. The cost to employers and the economy of these untreated individuals is staggering. Some employers have tried to address employees' emotional well being by establishing Employee Assistance Programs. Yet, even these programs do not sufficiently address existing barriers to the detection and treatment of mental health disorders in the workplace. This paper describes the design of an automated workplace program that uses an Interactive, computer-assisted telephonic system (Interactive Voice Response or IVR) to assess workers for a variety of mental health disorders and subsequently refers untreated and inadequately treated workers to appropriate treatment settings. PMID- 17283924 TI - An intelligent ballistocardiographic chair using a novel SF-ART neural network and Biorthogonal wavelets. AB - This paper presents a comparative analysis of novel supervised fuzzy adaptive resonance theory (SF-ART), multilayer perceptron (MLP) and Multi Layer Perceptrons (MLP) neural networks over Ballistocardiogram (BCG) signal recognition. To extract essential features of the BCG signal, we applied Biorthogonal wavelets. SF-ART performs classification on two levels. At first level, pre-classifier which is self-organized fuzzy ART tuned for fast learning classifies the input data roughly to arbitrary (M) classes. At the second level, post-classification level, a special array called Affine Look-up Table (ALT) with M elements stores the labels of corresponding input samples in the address equal to the index of fuzzy ART winner. However, in running (testing) mode, the content of an ALT cell with address equal to the index of fuzzy ART winner output will be read. The read value declares the final class that input data belongs to. In this paper, we used two well-known patterns (IRIS and Vowel data) and a medical application (Ballistocardiogram data) to evaluate and check SF-ART stability, reliability, learning speed and computational load. Initial tests with BCG from six subjects (both healthy and unhealthy people) indicate that the SF-ART is capable to perform with a high classification performance, high learning speed (elapsed time for learning around half second), and very low computational load compared to the well-known neural networks such as MLP which needs minutes to learn the training material. Moreover, to extract essential features of the BCG signal, we applied Biorthogonal wavelets. The applied wavelet transform requires no prior knowledge of the statistical distribution of data samples. PMID- 17283925 TI - The association between clinical pathways and hospital length of stay: a case study. AB - Clinical pathways are the treatment protocol in order to reduce or eliminate variation of care by specifying to nursing and medical staff. The effectiveness of the clinical pathways to accomplish this goal, however, is in question. With the implementation of the clinical pathways in 2001, this study evaluates the effectiveness of clinical pathway in reducing the inpatient length of stay in a rural hospital in a Midwestern state. All inpatient cases were used with the primary diagnoses of chronic obstructive pulmonary disease, congestive heart failure, diabetes, myocardial infarction, and pneumonia from the years of 1999 2003. By controlling for gender, age, insurance type, and year, this study employs a multiple regression analysis to evaluate the association between clinical pathways and the length of stay. Only one (the clinical pathway for myocardial infarction) out of the five pathways studied showed an association with a statistical significance in decreasing the length of stay. Health care administrators should consider other aspects as well as the hospital length of stays when implementing clinical pathways in their facility. PMID- 17283926 TI - Molyneux's answer II. PMID- 17283928 TI - Test of models of achromatic transparency. AB - Consider an achromatic disk transparent on an achromatic background formed by two adjoining rectangles, with the common border of the rectangles dividing the disk in half. Current models of achromatic transparency contend that the perceived extent of transparency of the disk depends on the luminance contrast inside the disk and on the luminance contrast in the background outside the disk. Here, a model is proposed which contends that this perceived extent is determined only by the luminance contrasts inherent in the disk: inside the disk and between the disk and the background. Two experiments were designed to determine which luminance contrasts influence transparency. In the first experiment, subjects rated the perceived extent of transparency of the disk for different combinations of the luminances of the disk and of the background. The results strengthen the view that the perceived extent of transparency depends on the luminance contrasts inherent in the disk. In the second experiment, a test was made of the possibility that luminance contrasts between adjoining areas of the background outside the disk are nonessential for transparency. The results show that transparency occurred both when the areas of the background outside the transparent region adjoined one another and when they were separated, confirming that the perceived extent of transparency depended only on luminance contrasts between adjoining areas inherent in the disk. PMID- 17283927 TI - The effect of spatial-frequency filtering on the visual processing of global structure. AB - In three experiments we measured reaction times (RTs) and error rates in identifying the global structure of spatially filtered stimuli whose spatial frequency content was selected by means of three types of 2-D isotropic filters (Butterworth of order 2, Butterworth of order 10, and a filters with total or partial Gaussian spectral profile). In each experiment, low-pass (LP), bandpass (BP), and high-pass (HP) filtered stimuli, with nine centre or cut-off spatial frequencies, were used. Irrespective of the type of filter, the experimental results showed that: (a) RTs to stimuli with low spatial frequencies were shorter than those to stimuli with medium or high spatial frequencies, (b) RTs to LP filtered stimuli were nearly constant, but they increased in a nonmonotonic way with the filter centre spatial frequency in BP filtered stimuli and with the filter cut-off frequency in HP filtered stimuli, and (c) the identification of the global pattern occurred with all visible stimuli used, including BP and HP images without low spatial frequencies. To remove the possible influence of the energy, a fourth experiment was conducted with Gaussian filtered stimuli of equal contrast power (c(rms) = 0.065). Similar results to those described above were found for stimuli with spatial-frequency content higher than 2 cycles deg(-1). A model of isotropic first-order visual channels collecting the stimulus spectral energy in all orientations explains the RT data. A subsequent second-order nonlinear amplitude demodulation process, applied to the output of the most energetic first-order channel, could explain the perception of global structure of each spatially filtered stimulus, including images lacking low spatial frequencies. PMID- 17283929 TI - Perceptual transparency in 3- to 4-month-old infants. AB - We examined perceptual transparency in infants. In a previous study, Johnson and Aslin (2000 Developmental Psychology 36 808 - 816) found that 4-month-olds could perceive transparency in a moving chromatic display, but not in an achromatic display. In this study, we further examined perceptual transparency in infants using a static achromatic display. Considering the development of figural organisation and contrast sensitivity, we assumed that 3- to 4-month-olds would perceive transparency even in a static achromatic display. We created a transparency and a non-transparent display composed of a partially overlapping circle and square, by switching the colours. Infants aged 3 to 4 months (n = 24) were familiarised with the transparency display (experiment 1) or with the non transparent display (experiment 2). Then, they were confronted with a uniform colour and a two-colour figure. Infants showed novelty preference for the two colour figure after they had been familiarised with the transparency display (experiment 1), but not after they had been familiarised with the non-transparent display (experiment 2). These results suggest that 3- to 4-month-old infants can perceive transparency in a static achromatic display. PMID- 17283930 TI - Face recognition in pictures is affected by perspective transformation but not by the centre of projection. AB - Recognition of unfamiliar faces is susceptible to image differences caused by angular sizes subtended from the face to the camera. Research on perception of cubes suggests that apparent distortions of a shape due to large camera angle are correctable by placing the observer at the centre of projection, especially when visibility of the picture surface is low (Yang and Kubovy, 1999 Perception & Psychophysics 61 456-467). To explore the implication of this finding for face perception, observers performed recognition and matching tasks where face images with reduced visibility of picture surface were shown with observers either at the centre of projection or at other viewpoints. The results show that, unlike perception of cubes, the effect of perspective transformation on face recognition is largely unaffected by the centre of projection. Furthermore, the use of perspective cues is not affected by textured surfaces. The limitation of perspective in restoring 3-D information of faces suggests a stronger role for image-based, rather than model-based, processes in recognition of unfamiliar faces. PMID- 17283931 TI - A study of impaired judgment of eye-gaze direction and related face-processing deficits in autism spectrum disorders. AB - The purpose of this study was to examine whether individuals with autism spectrum disorders (ASD) use the same cognitive strategies as typically developing individuals when processing eye-gaze direction. Subjects viewed pictures of whole faces, the eye region alone, and pairs of arrows presented for 40, 70, or 100 ms, and responded according to the direction the eyes were looking or the arrows pointing (left, right, or straight ahead). Experiment 1 demonstrated that typically developing adults (n = 41) were more accurate and showed shorter reaction times when judging direction of averted eye gaze in the context of the whole face than when only the eyes were visible (eye-region-alone condition). Furthermore, in the eye-region-alone condition participants were more accurate and faster at judging direct eye gaze than averted eye gaze. The same task was used in experiment 2 to compare the performance of a group of individuals with ASD (n = 24) with that of a group of IQ-matched typically developing individuals (n = 26). The performance of the control participants was identical to that observed in experiment 1. Individuals with ASD were able to judge eye-gaze direction accurately at short exposure duration; however, they failed to show the typical advantage for judging averted gaze in whole faces and the increased sensitivity to direct gaze in the eye-region-alone condition. The findings are discussed in terms of impairments to discrete gaze-processing and face-processing mechanisms, and the connectivity between these mechanisms. PMID- 17283932 TI - Color onsets and offsets, and luminance changes can cause change blindness. AB - It has recently been demonstrated that people often fail to detect between-view changes in their visual environment. This phenomenon, called 'change blindness' (CB), occurs whenever the perceptual transient that usually accompanies a change is somehow blocked, or made less salient. In the well-known flicker paradigm, the transient is blocked by inserting a blank screen between the original and changed scenes. We tested whether transients that do not involve the appearance or disappearance of visual objects would also produce CB. Therefore we tested whether the appearance or disappearance of color information, and increments or decrements in luminance, could cause CB. In three experiments, subjects searched for changes in natural scenes. We found that both color transients and luminance transients significantly reduced change detection (by approximately 30%) relative to a no-transient condition. PMID- 17283934 TI - Body mass index and waist: hip ratio are not enough to characterise female attractiveness. AB - The assessment of characteristic body features of Miss Poland beauty contest finalists compared with the control group, can contribute to recognising the contemporary ideal of beauty promoted by the mass media. The studies of Playboy models and fashion models conducted so far have been limited to the following determinants of attractiveness: body mass index, waist:hip ratio, and waist:chest ratio, which only partially describe the body shape. We compared 20 body features of the finalists of Miss Poland 2004 beauty contest with those of the students of Medical Academy in Bydgoszcz. Discriminant analysis showed that the thigh girth height index, waist: chest ratio, height, and body mass index had the greatest discrimination power distinguishing the two groups. A model of Miss Poland finalists figure assessment is presented which allows one to distinguish super attractive women from the control group. PMID- 17283935 TI - Are olfactory images sensory in nature? AB - We investigated the features of olfactory mental images by comparing odour images with perceptual and semantic representations. Participants who were assigned to three groups made similarity judgments about 17 common odours by smelling odours, imagining odours, or on the basis of the meaning of odour source names. In the smelling group, every pair of odours was compared. In the imagining group, imagined odours were compared twice, both before and after associative learning of the odour/name combinations. In the meaning group, the odour source names were compared in terms of general word meanings. Nonmetric multidimensional scaling analysis was applied to each group of similarity data and three-dimensional sensory, mental, and semantic spaces were composed. 17 elements in the mental and semantic spaces were superimposed onto the sensory space by Procrustes rotation. We found that the averaged distances of the 17 elements between the sensory and the mental spaces (either before or after learning) were smaller than those between the sensory and semantic spaces. We suggest that odour images have sensory features, especially after associative learning between perceived odours and their names. PMID- 17283933 TI - The perceived structural shape of thin (wire-like) objects is different from that of silhouettes. AB - Observers are faster at judging the position of convex vertices compared to concave vertices. This is believed to be due to an explicit representation of position for visual parts. The best evidence comes from comparing the same contours perceived as either figures or holes, because this is a pure figure ground reversal (Bertamini and Croucher, 2003 Cognition 87 33 - 54; Bertamini and Mosca, 2004 Perception 33 35-48). Specifically, an interaction is present between type of object (object or hole) and shape. One assumption is that the contour of a silhouette is perceived as the rim of a solid object. It follows that a different pattern should be found for thin (wire-like) objects compared to silhouettes. We confirm this difference in three experiments. We argue that this is due to the perceived parts when contours can be interpreted as self-occlusion rims. PMID- 17283937 TI - Patients' concerns about medical errors during hospitalization. AB - BACKGROUND: A clear understanding of patients' understanding and perceived risk of medical errors is needed. Multiwave telephone interviews were conducted in 2002 with 1,656 inpatients from 12 Midwestern hospitals regarding patients' conceptualization of medical errors and perceived risk of seven types of medical errors. RESULTS: Patients defined medical errors to include not only clinical mistakes but also falls, communication problems, and responsiveness. Ninety-four percent of respondents reported their medical safety as good, very good, or excellent, but 39% experienced at least one error-related concern, most commonly medication errors (17% of respondents), nursing mistakes (15%), and problems with medical equipment (10%). Frequency of concerns was associated with reduced willingness to recommend the hospital (p < .001). DISCUSSION: If patients' definition of medical errors is broader than the traditional medical definition, providers should clarify the term "error" to ensure effective communication. Most patients felt a high level of medical safety but a sizeable proportion experienced a concern about an error during hospitalization. The selective nature of concerns and the impact of patient and hospital characteristics provide insight into ways to engage patients in error prevention programs. PMID- 17283936 TI - The Poggendorff illusion: premeditated or unpremeditated misbehaviour? AB - Poggendorff illusions have sometimes been explained as arising in a two-stage process, with misalignment consequent upon prior, independently observable misjudgments of angle, extent, or proportion. However, several misalignments combined in one figure can be arranged so that if such prior illusions were the cause, they would have to transform simultaneously in opposed directions to save appearances. When Poggendorff misalignments are deliberately embedded in other illusions, results are intriguingly various, but the comparison of Poggendorff figures with and without associated illusions suggests that the underlying misalignments arise from pre-attentive cues, local to each traverse across a gap. PMID- 17283939 TI - Registration-associated patient misidentification in an academic medical center: causes and corrections. AB - BACKGROUND: Proper patient identification is a major factor affecting patient safety in any health care organization. METHODS: An interdisciplinary team, using three Plan-Do-Study-Act (PDSA) cycles, reviewed the incidence of patient misidentifications resulting from registration process errors. Retrospective and prospective data were collected to determine the incidence among inpatients and outpatients. RESULTS: Registration-associated patient misidentification errors occurred 7 to 15 times per month. Information systems deficiencies, inadequate training, and the lack of a single master patient index were among the root causes identified. After three PDSA cycles, the incidence rate for registration associated patient misidentification errors declined for inpatients (80.5%) but increased for outpatients (30.2%). DISCUSSION: Through an iterative process as implied in the PDSA cycle, registration-associated patient misidentification errors for established Johns Hopkins Hospital patients were dramatically reduced. A checklist is provided for other organizations to assess their vulnerability to registration-associated patient misidentification errors. The checklist suggests, for example, that organizations strive to develop a single master patient index and limit access to registration systems to staff with proper training and performance expectations. PMID- 17283938 TI - Eliminating birth trauma at Ascension Health. AB - BACKGROUND: Ascension Health identified perinatal safety as one of eight priorities for action in a systemwide effort to achieve zero preventable injuries and deaths by July 2008. IMPLEMENTATION: Three alpha sites developed and implemented transformational practices aimed at eliminating preventable birth trauma. Standardized order sets linked to all major areas of obstetrical care were either updated or developed and then tested and incorporated into the work flow of the labor and delivery units. Best practices were shared via team meetings and conference calls. Each site created systems to ensure that evidence based practices were reliably followed for high-risk conditions associated with perinatal harm, that robust strategies for communication were adopted, and that collaborative practice was promoted among caregivers. RESULTS: By June 2006, all facilities achieved birth trauma rates that were at or near zero in conjunction with the implementation of these practices. DISCUSSION: Three alpha sites of differing size, patient demographics, and available resources, using a combined uniform and facility-specific approach, achieved a significant reduction in the incidence of birth trauma. Yet each site adopted unique site-specific processes designed to enhance practice on the basis of unit or institutional culture, market challenge, and/or the prospect for success. PMID- 17283940 TI - Communication failure: basic components, contributing factors, and the call for structure. AB - BACKGROUND: Communication is a taken-for-granted human activity that is recognized as important once it has failed. Communication failures are a major contributor to adverse events in health care. BASIC COMMUNICATION COMPONENTS AND PROCESSES: The components and processes of communication converge in an intricate manner, creating opportunities for misunderstanding along the way. When a patient's safety is at risk, providers should speak up (that is, initiate a message) to draw attention to the situation before harm is caused. They should also clearly explain (encode) and understand (decode) each other's diagnosis and recommendations to ensure well coordinated delivery of care. INDIVIDUAL, GROUP, AND ORGANIZATIONAL FACTORS: Beyond basic dyadic communication exchanges, an intricate web of individual, group, and organizational factors--more specifically, cognitive workload, implicit assumptions, authority gradients, diffusion of responsibility, and transitions of care--complicate communication. THE CALL FOR STRUCTURE: More structured and explicitly designed forms of communication have been recommended to reduce ambiguity, enhance clarity, and send an unequivocal signal, when needed, that a different action is required. Read-backs, Situation-Background-Assessment-Recommendation, critical assertions, briefings, and debriefings are seeing increasing use in health care. CODA: Although structured forms of communication have good potential to enhance clarity, they are not fail-safe. Providers need to be sensitive to unexpected consequences regarding their use. PMID- 17283941 TI - The Objective Structured Clinical Examination as an educational tool in patient safety. AB - BACKGROUND: The Objective Structured Clinical Examination (OSCE) is an assessment tool characterized by the use of "lay" people trained to respond to questions in a standardized fashion. The learner's performance is observed and scored against a checklist of responses or behaviors. An OSCE station related to the communication and management of prescription errors was introduced in 2003 as part of a quality improvement (QI) curriculum at Mayo Medical School. METHODS: All 42 third-year medical students took part in this pilot study, which was designed to evaluate the usefulness of an OSCE station as an assessment and educational tool for managing prescription errors. RESULTS: Thirty-three (76.7%) students agreed that the OSCE station enhanced their awareness of medication errors. Thirty (71.4%) students felt that their comfort level with communicating prescription errors to patients increased. Specific feedback regarding root cause analysis, collaboration with the pharmacist for error analysis, interpersonal and communication skills feedback from the faculty, and use of the standardized patient and of an actual prescription that led to a medication error, were found especially valuable. DISCUSSION: This pilot study demonstrates the potential use of the OSCE as an assessment and educational tool in QI and patient safety. The OSCE approximates a "live clinical setting" and provides an opportunity for the assessment of situational awareness and response, as well as formative and summative feedback to students. PMID- 17283942 TI - Medical emergency team calls: the need to communicate a resuscitation plan. AB - As illustrated in the case report of a 79-year-old woman, actions can be taken to ensure that the rapid response system is not used as the surrogate "do not actively resuscitate" team. PMID- 17283943 TI - Cr(VI) and Cr(VI)-diphenylcarbazide removal from aqueous solutions using an iron rotating disc electrode. AB - This paper presents the results of the investigation on the removal of Cr(VI) and the complex Cr(VI)-diphenylcarbazide from aqueous solutions using an electrochemical reactor, with iron electrodes. A maximum value of 99% Cr(VI) removal from aqueous solutions is observed for both Cr(VI) and Cr(VI) diphenylcarbazide, at initial concentrations from 150 to 800 mg l(-1). Cyclic voltammetry experiments of water show the presence of electroactive species in the oxidation and reduction zones previous to the treatment and how this presence diminishes as the electrochemical treatment is applied to the wastewater. UV-Vis analyses corroborate the improvement on the quality of aqueous solutions treated. Finally, scanning electron microscopy and energy dispersion spectra show that Cr and Fe are present as constituents of the sludge formed during the electrochemical treatment. It was demonstrated that the use of electrochemical methods for the treatment of Cr(VI) and Cr(VI)-diphenylcarbazide aqueous solutions is an effective and economical method. PMID- 17283944 TI - Solvent release into a sandy aquifer 3: enhanced dissolution by methanol injection. AB - A field experiment involving a release of 5 litres of a mixture of chlorinated solvents (0.5 l of chloroform, 2.0 l of trichloroethylene, and 2.5 l of tetrachloroethylene) was carried out in a sandy, unconfined, shallow aquifer at Canadian Forces Base Borden, east of Toronto, Ontario, Canada. The dissolution of the chlorinated solvents into the groundwater was studied in detail for 220 days, then a methanol/water mixture was injected to study the possible enhancement of the dissolution. An effect of the methanol injection was only observed at a few sampling points, likely due to the distribution of the solvent as a laterally extensive, thin pool. This investigation shows that it is crucial to know the exact location of the dense nonaqueous phase liquids (DNAPL) in the subsurface when designing and performing remedial techniques at contaminated sites. PMID- 17283945 TI - [Effect and bioaccumulation of heavy metals (Zn, Cd) on Micractinium pusillum ALGA]. AB - Heavy metals (Zn and Cd) effect and their bioaccumulation by a microalga Micractinium pusillum were investigated. Results showed that Cd was more toxic than Zn on Micractinium pusillum. Indeed, inhibitory concentrations of 50% of alga population in 72h (IC(50,72h)) were 0.28 and 0.34 mg l(-1) respectively for Cd and Zn. On the other hand, metal extracted rates from medium solution were more important for Zn than for Cd, essentially for the two first concentrations tested (0.06 and 0.12 mg l(-1)). Furthermore, Zn and Cd extracted proportions were more important for the low concentrations tested and decreased progressively with increasing concentrations applied. This mechanism of extraction corresponds principally to their biosorption by Micractinium pusillum. PMID- 17283946 TI - Estimating pollutant removal requirements for landfills in the UK: III. Policy analysis and operational implications. AB - The policy analysis and management implications for achieving landfill equilibrium status within a sustainable timescale (decades rather than centuries) are presented based on modelled results reported previously. Until relatively recently, timescale estimates suggested that equilibrium or landfill completion could be achieved within 40-60 years i.e. the same order of magnitude as financial provision for aftercare. However results of modelling in this study (reported in previous paper) suggest that timescales may be considerably longer (many centuries in some instances) suggesting that financial provision may be inadequate. The role of the most promising and available waste treatment technologies and strategic waste management options in contributing towards achieving equilibrium status are discussed. Results suggest that a re-examination of techniques for accelerating landfill stabilisation, including aerobic and bioreactor landfill, is warranted. PMID- 17283947 TI - Treating sewage using coimmobilized system of Chlorella pyrenoidosa and activated sludge. AB - Chlorella pyrenoidosa was coimmobilized with activated sludge to produce algae bacteria beads for sewage treatment. Hydrolysis/acidogenesis pretreatment could improve the symbiotic microenvironment of coimmobilized Chlorella pyrenoidosa and activated sludge, and as a result, promote the removal of nutrients (COD(cr), inorganic nitrogen and inorganic phosphorus) in the sewage. A photo-bioreactor combining hydrolysis/acidogenesis pretreatment and coimmobilized technique was designed to treat sewage continuously. The results show that, the removal efficiencies of COD(cr), NH4(+)-N and TP reached steady state after 4-days of experiment. The removal efficiencies of COD(cr), NH4(+)-N and TP were 59.6%, 59.0% and 60.3% respectively. PMID- 17283948 TI - The effect of microwave electromagnetic radiation on organic compounds removal efficiency in a reactor with a biofilm. AB - This article shows the results of research on microwave radiation as a factor affecting organic compounds removal in a reactor with a biofilm. In the experiment a bioreactor was situated inside a microwave tube and there exposed to radiation. Municipal wastes were supplied to the bioreactor from a retention tank, to which they returned having passed through the reactor's packing. The whole system operated in a time cycle comprising a 24-hour detention of the wastewaters supply. The research was based on the specific properties of microwave heating, i.e. their ability to heat only the substances of appropriate dielectric properties. As the reactor was properly constructed and the microwave generator work was synchronised with that of the volumetric pump, microwave energy was directed mostly to the biofilm. It was observed that as a result of microwave radiation the process of organic compounds removal, defined as Chemical Oxygen Demand COD, increased its rate nearly by half. Simultaneously the process efficiency increased by 7.7% at the maximum. While analysing the changes the organic compounds underwent it was revealed that the load in-built in the biomass decreased by over half as a result of microwave radiation input at 2.5 W s(-1), which was optimal under the experimental conditions. Similarly the amount of pollutant remaining in the treated effluent decreased nearly by half, whereas the role of oxidation in removing organic pollutant increased in excess of 25% when compared to the control system. PMID- 17283949 TI - An investigation into solvent extraction of pcbs from weathered soils. AB - Laboratory investigations were conducted to study the efficiency of extraction of polychlorinated biphenyls (PCBs) from weathered soils by polar organic solvents i.e. acetone, isopropanol (IPA) and methanol that were chosen for lower hazard and for penetration in wet soil. The impacts of hydrogen peroxide pretreatment, soil-solvent ratio and number of extraction cycles on PCBs extraction efficiency were investigated. The pretreatment of soil with hydrogen peroxide (H2O2) prior to extraction improved PCB extraction efficiency. An enhancement in extraction efficiencies was also observed with an increasing number of extraction cycles and at lower soil-solvent ratio. All three solvents could recover Aroclor 1254 (> 73%) from the weathered soils with multicycle extractions. PMID- 17283950 TI - Soil-based treatment of partially treated liquid swine manure. AB - A soil-column system was tested for the removal of soluble organics and nutrients from partially treated liquid swine manure. The liquid manure was applied to the 900 mm deep (300 mm of local topsoil and 600 mm of local subsoil) soil columns continuously for an eight-week period, and leachate as well as soil samples were analysed. An effective liquid manure application rate of 17 mm d(-1) was determined based on a preliminary liquid manure soil-based treatment experiment. It was found that more than 90% of five-day biochemical oxygen demand, chemical oxygen demand, total Kjeldahl and ammonia nitrogen, and total phosphorus could be effectively removed from the liquid manure by the soil system. Nitrogen contents accumulated in the soil matrix mostly within the 0 to 300 mm depth, while no significant increase was observed in sub soils. Soil analyses indicated the occurrence of nitrification and denitrification in the soil columns. Nitrogen balance showed that about 42% of the applied nitrogen was lost from the system during the liquid manure soil-based treatment experiment, suggesting the emission of ammonia and other gaseous nitrogen generated through nitrification and denitrification. The leachate of the soil treatment system was used to irrigate Bermuda grass. No negative effect of leachate was observed on the plant growth. PMID- 17283951 TI - [Impact of mining wastes on the physicochemical and biological characteristics of groundwater in a mining area in Marrakech (Morocco)]. AB - Metal sulphide tailings represent a potential risk basically for the environment and particularly for water resources, because of their natural oxidisability which leads to the production of acid/neutral mine drainage. The prospected site close to Marrakech includes zinc, lead and copper sulphide deposits. This site is located in an agricultural area where ground water is used both for irrigation and drinking. Eco-toxicological investigations have been undertaken in order to asses the tailings impact on water quality in nearby wells. These investigations include physico-chemical characterization of the groundwaters as well as faunistic population determination. As compared to standard wells, waters from the wells located downstream of the mining site, have high electrical conductivities and high major ions contents, which can reach: 755 mg l(-1) in SO4(2-), 1670 mg l(-1) in Ca2+, 528 mg l(-1) in Mg2+, 2289 mg I(-1) in Na+ and 14981 mg l(-1) in Cl-. The fauna distribution analysis carried out around the studied wells shows qualitative and quantitative differences according to the flow gradient of the groundwaters. Areas located upstream of the mine tailings site are richer in stygobite species (Type and quantity) than those located downstream or close to it. It is likely that these biological differences are due to water quality alteration induced by the mining activity. PMID- 17283952 TI - Phosphate recovery potential from wastewater by chemical precipitation at batch conditions. AB - This study aimed to investigate the potential for phosphate recovery, instead of removal, from wastewater at conventional biological treatment processes. In the first part of this study, struvite and apatite phosphate-salts formation potential were investigated using artificially prepared solutions. In the second part, real municipal wastewater was subjected to batch-basis aerobic/anaerobic sequential order operation and supernatant of high phosphate-concentrations released into the liquid medium during the anaerobic phase were withdrawn and subjected to chemical precipitation tests. The formed mixed-liquor suspended solid suspensions were subjected to quiescent settling to ensure the separation of solids. Then, to form chemical bonds between calcium and phosphate ions, calcium was added to the withdrawn supernatants. The ability of apatite formation by itself as well as support-aided apatite formation was tested in supernatants. All the precipitation tests were carried out at orbital incubator at constant 20 degrees C and 25 degrees C temperature which were reported to be the range yielding the highest phosphate precipitation efficiency. In order to evaluate the solid-liquid separation ability of the chemical slurries, both centrifugation at 2000 rpm and membrane filtration at 100 mbar vacuum pressure were tested. The recovered solid phases as well as supernatants were analyzed for phosphate contents and it was revealed that the highest efficiency of phosphate precipitation was at pH of 9.50 for apatite and 9.40 for struvite. The results also suggested that struvite precipitation is more applicable for technical purposes while apatite precipitation is more applicable for economical reasons. PMID- 17283953 TI - Removal of geosmin and MIB by biofiltration--an investigation discriminating between adsorption and biodegradation. AB - Geosmin and 2-methylisoborneol (MIB) are two substances causing earthy/musty odours that are difficult to remove by conventional chemical drinking water treatment. In this study removal of geosmin and MIB by biofiltration of untreated surface water was investigated using granular activated carbon (GAC) and crushed expanded clay (EC) as filter media. Biofiltration through both GAC and EC removed geosmin and MIB present at low (20 ng l(-1)) concentrations by at least 97% at an empty bed contact time of 30 minutes and a temperature of 15 degrees C. At lower temperature (6-12 degrees C) and simultaneously lower biomass concentrations, removal efficiency was similar in the GAC but considerably lower in the EC biofilter, pointing to a second mechanism different from biodegradation. Consequently, microbial activity was suppressed with azide to enable discrimination between biodegradation and adsorption. During azide dosage, the GAC biofilters still removed geosmin and MIB nearly unaffectedly. In the EC biofilter, however, removal of both odorants ceased completely. Methylene blue adsorption confirmed that the GAC, even after almost four years of operation receiving surface water, had capacity to remove geosmin and MIB by adsorption. Since odour episodes commonly occur during the warm season when microbiological activity is high, EC constitutes a viable option as carrier medium for direct biological filtration of surface water. The additional GAC adsorption capacity however adds robustness to the removal process. PMID- 17283954 TI - Boron removal from wastewater using adsorbents. AB - In the present study, boron adsorption on activated alumina and activated carbon impregnated with calcium chloride, tartaric acid and mannitol was investigated. The adsorbate in question was the wastewater from the chemical landfill in Tarnowskie Gory of 25-70 mg l(-1) boron content. The removal of boron from the above-described wastewater was examined in the static (batch) and dynamic (column) experiments. The static experiments were carried out to assess boron adsorption isotherms, based on which the most efficient adsorbent as well as the rough resin load was determined. On the basis of the dynamic experiment results, the boron adsorptive capacities of the examined resins were deduced. It was concluded that the use of the impregnants increased the ability of activated carbon to adsorb boron. Granulated activated carbon WG-12 impregnated with mannitol was found to be the most promising for the boron removal from wastewater of the Chemical Wastewater Plant in Tarnowskie Gory. PMID- 17283955 TI - Identification of type and causes of filamentous bulking under Mediterranean conditions. AB - A national survey to identify the most common filamentous microorganisms in Greek wastewater treatment plants, to assess the extent of filamentous bulking phenomenon and to correlate the occurrence of these bacteria to specific operating parameters, was carried out for five years. According to the conclusions of this survey filamentous bulking is a widespread phenomenon in Greek wastewater treatment plants. Almost 70% of the sludge samples examined exhibited filament indices greater than 4 during the winter period. The most common filamentous species found in a decreasing order were M. parvicella, Type 0092, GALOs, Type 0041 and N. limicola. A seasonal variation of the composition of the biomass was observed. M. parvicella is the dominant species during winter periods, while T0092 is the dominant species during summer conditions. This seasonal pattern of biomass composition was followed by a similar seasonal variation of the settling characteristics in terms of Filament Index (FI) and Sludge Volume Index (SVI) values. M. parvicella's proliferation is favored in Carrousel and oxidation ditches systems especially when primary settling stage was preceeded, whereas its growth is also highly stimulated in intermittent aeration systems, even in the absence of primary settling tanks. Finally there is evidence that Bio-P systems without primary sedimentation inhibit its growth. PMID- 17283956 TI - Our first child was incompatible with life: understanding miscarriage as a lived experience. AB - Miscarriage as a medical experience is removed several times from the lived experience of a mother, partner and family. Often there is no space to grieve and mourn to facilitate that. In this article it will be shown that the lived experience of a miscarriage challenges the notion of care and loss forever. Ask a woman the memory is always there and very often the pain. It's important to let the wisdom of sadness speak and emotions to flow unhurried. Emotions need to be set free. What is less appreciated is that professional carers often feel at a loss themselves and they too need love and support. Staff and relatives are sometimes in different contexts of awareness and information about diagnosis and all aspects of care often need to be translated The experience of loss is not only related to death but to loss of hope, dreams, function and handing over care to another carer. Dealing with loss is a feature of being human, but dealing with multiple losses is sadly often a part of being a practicing nurse and midwife. It is time to really appreciate what it means to live through a miscarriage. What we need now to do is move beyond a medical experience into creating a space where a woman can feel safe and loved to grieve for all that is lost and all that could have been. PMID- 17283957 TI - Suffer no more in silence: challenging the myths of women's mental health in childbearing. AB - This article will challenge some of the myths surrounding women's mental health in childbearing. Pregnancy and the aftermath are very often seen as a time of joy and happiness. Yet for a significant amount of women at least ten per cent childbearing represents major emotional and psychological adjustment (Stowe et al.2005) and sadly mental health problems like post-natal depression and puerperal psychosis. It will be shown that there continues to be a need to develop new methods of caring for this client group and more women centred services. It is vital to organise and mobilize appropriate services that can assist and listen to individual women with mental health problems. It is important that women have services and space to explore their emotional and psychological problems and not have to suffer in silence. To promote mental health in childbearing their needs to be a clear emphasis in midwifery and medical education on understanding mental health in it's broadest sense. This requires developing midwifery care to where possible include partners and other family members in aiding recovery. A major step in promoting mental health is respecting the knowledge, presence and healing hands of both skilled midwives and nurses. Mental health nurses and midwives are aware of the deficits in services and care provision for women with psychological distress and mental health problems (Murray & Hamilton 2005). Care practices need to be informed by relevant interpersonal skills, research, education, prevention work, and a system of early detection and treatment of mental health problems (Cuijpers et al. 2005). PMID- 17283958 TI - Appreciating the importance of history: a brief historical overview of mental health, mental health nursing and education in Australia. AB - History is consistently acknowledged as crucial to the identity of a profession. In the case of mental health nursing this is perhaps more so, as published accounts of the history of nursing rarely pays attention to the specialty of mental health. The aim of this paper is to provide a brief overview of the history of mental health nursing in Australia. It is concluded that an understanding of history is essential in understanding and interpreting contemporary mental health service delivery and seeking to overcome the professional distance between mental health and other branches of nursing. PMID- 17283959 TI - Cognitive-attitudinal aspects of key-worker's talk about their patients in forensic psychiatric institutions. AB - SCOPE: Within an international network study involving four European countries (COMSKILLS), results on clinical-qualitative data are reported and discussed. A total of 103 semi-structured interviews were conducted, representing 45 per cent of the patients involved in the project (N=231). METHOD: The coding framework represents a means of identifying and measuring aspects of complexity and specificity in the way in which key workers talk about care in relation to individual patients. RESULTS: Respondents talked about patient care most frequently in terms of coping behavior and working relationships with patients. The commonest method cited for information gathering was observation. Out of three conceptual levels, ranging from complex and specific responses (conceptual level 3), to relatively general and unspecific remarks (level 1), most responses were coded at Levels 1 or 2. CONCLUSIONS: Taking into account the apparent reluctance of many clinical staff to make use of standardized assessment instruments, systematic treatment-oriented methods able to both allow for valid and reliable assessments and to structure clinical experience is needed. It is expected that complexity and specificity care is referred to will profit from the regular use of such a method (e.g. the BEST-Index). PMID- 17283960 TI - Mental health nursing roles and functions in acute inpatient units: caring for people with intellectual disability and mental health problems--a literature review. AB - The purpose of this paper is to review current national and international perspectives on the role and function of mental health nursing in dual disability within acute mental health inpatient settings. A universally accepted definition of the role and function of psychiatric nursing has been elusive. The role and function may be presumed to have core attributes that differ according to local conditions. The articulation of the role and function will contribute to the body of knowledge of psychiatric nursing and to improving the understanding of the nurse-patient relationship for those caring for people with dual disability in acute mental health inpatient facilities. The two identified key roles and functions of mental health nursing practice for people with intellectually disabilities within acute inpatient mental health facilities in Victoria will be discussed. PMID- 17283961 TI - The efficiency of X-ray microanalysis in low-vacuum scanning electron microscope: deposition of calcium on the surface of implanted hydrogel intraocular lens (IOL). AB - To examine the calcification of implanted hydrogel IOL by X-ray microanalysis, we compared conventional transmission electron microscopy (TEM) with low-vacuum scanning electron microscopy (SEM). We also compared metal coating with non metal coating in low-vacuum SEM. Calcification of IOL showed deposits which were located in the superficial substance of lens. In conventional TEM and X-ray microanalysis, calcium, phosphate and silicon were detected in the deposits. In low-vacuum SEM, the deposits detected in metal coating were calcium, phosphorus, sodium and magnesium, but not silicon. However, in non metal coating, the deposits contained not only calcium, phosphorus, silicon, sodium and magnesium, but also fluoride, aluminum and argentums. It was concluded that in conventional TEM where a specimen is fixed and dehydrated in ethanol, various elements leak out. On the other hand, when a specimen is coated with carbon and gold palladium for SEM, light elements might not be detected in X-ray microanalysis. Low-vacuum SEM preparation does not need metal coating and low-vacuum SEM appears to provide a highly efficient method for X-ray microanalysis. PMID- 17283962 TI - Transfection of eggs in the bivalve mollusc Chamelea gallina (Bivalvia, Veneridae). AB - Eggs from the bivalve mollusc Chamelea gallina were transfected in vitro. The p GeneGrip gene construction that expresses the green fluorescent protein (GFP) was employed. It was necessary to remove the jelly coat which covers the egg surface for a successful transfection, and then 44.2% of gametes appeared transfected after using naked DNA. On the other hand, cationic liposomes (Lipofectamine) and neutral lipids (GenePORTER) were employed as gene vectors. After the employ of Lipofectamine 35.6% of eggs were transfected and 41.4% after using GenePORTER. Fluorescence analysis showed that the foreign gene appeared principally located in the egg cytoplasm, but laser confocal microscopy showed that it was also present in the nucleus. Furthermore, PCR analysis demonstrated that the foreign DNA appeared in the DNA extracted from the treated eggs. This simple method for the transfection of mollusc eggs would be interesting for future biotechnological applications in species of commercial interest. PMID- 17283963 TI - Sperm activation and sperm-egg interaction. AB - Different steps of sperm activation such as acrosomal reaction and capacitation are described in details. The molecules involved in sperm-egg interaction are also reported. PMID- 17283964 TI - Nerve cell death types in the edematous human cerebral cortex. AB - Cortical biopsies of 18 patients with clinical diagnosis of congenital hydrocephalus, brain trauma, and vascular anomaly were examined with the transmission electron microscope to study the distinct and overlapped morphological cell types of nerve cell death in the human edematous cerebral cortex. The nerve cells showed lobulated and shrunken nucleus, irregular enlargement and fragmentation of perinuclear cistern, with areas of apparently intact nuclear pore complexes alternating with regions of nuclear pore complex disassembly. The nucleolus appears unaltered in moderate edema and with distorted nucleolar subcompartments in severe edema. Most nonpyramidal nerve cells, astrocytes and oligodendrocytes underwent an oncotic-apoptotic-necrotic continuum featured by swollen nucleoplasm, cytoplasm, and cell organelles, chromatin condensation and marginalization, and formation of apoptotic bodies. In a lesser proportion other nonpyramidal nerve cells, astrocytes and oligodendrocytes only showed apoptosis or oncosis. Autophagic cell death characterized by presence of autophagic vacuoles of lysosomal origin was rarely seen. The above findings suggest that different mechanisms of nerve cell death occur in the human edematous cerebral cortex related with brain trauma, congenital hydrocephalus, vascular anomaly, and their anoxic-ischemic conditions. An oncotic-apoptotic continuum process leading to necrosis predominates in human cerebral cortex nerve cell populations. The nerve cell death is discussed in relation with the severity of brain edema, anoxic-ischemic conditions of brain parenchyma, oxidative stress, glutamate excitotoxicity, calcium overload, and caspase dependent and independent mechanisms. PMID- 17283965 TI - Ultrastructural study of the epididymis and the vas deferens and electrophoretic profile of their luminal fluid proteins in the lizard Mabuya carinata. AB - The light microscopy, histochemical and TEM studies of the epididymis and the vas deferens revealed the presence of PAS positive secretory granules in the epithelial cells lining the lumen of these organs. One dimensional SDS gel electrophoretic pattern of luminal fluid proteins and the total protein content of the testis, three regions of the epididymis and the vas deferens of the lizard, Mabuya carinata were studied during breeding and nonbreeding season of the reproductive cycle. During breeding season, 25 protein bands in the testicular luminal fluid, 26 in the anterior epididymal luminal fluid and 28 in the middle and posterior epididymal luminal fluid were found. Ten new protein bands appeared in the anterior epididymal region whereas five new protein bands appeared in the middle region of the epididymis indicating regional difference in protein secretions of the epididymis. Vas deferens luminal fluid showed the highest number of protein bands (32) and the highest total protein content (9.07 mg/ml) compared to the testis and the epididymis. Four new protein bands appeared in the vas deferens. Number of protein bands in the luminal fluids of testis, epididymis and the vas deferens were significantly reduced during nonbreeding season compared to those of the breeding season. Consistent with the decrease in the number of protein bands, there was a significant reduction in the total protein concentration in all the tissue samples during nonbreeding season. The results indicate seasonal differences in number of proteins secreted and quantity of proteins in the luminal fluid of male reproductive tract of M. carinata. This is the first study in reptiles revealing appearance of new proteins in epididymis, and vas deferens by conducting simultaneous electrophoretic profile of testicular, epididymal and vas deferens luminal contents. PMID- 17283966 TI - Ultrastructural sperm study in infertile males with microdeletions of Y chromosome. AB - A retrospective study to detect specific Y chromosome microdeletions and to evaluate sperm ultrastructural characteristics in infertile men was set up. We selected 219 infertile men referred to Regional Referral Center for Male Infertility, Siena, Italy for semen analysis from January 1999 to April 2004. Family history, lymphocyte karyotype determination, Y microdeletion screening, physical examination, hormonal assays, semen analysis were carried out. Sperm concentration and progressive motility, ultrastructural analysis of sperm organelles, PCR amplification of sequence tagged sites for Y microdeletion screening were performed. Different Y-chromosome deletions were found, mainly in the AZFb and AZFc regions. Severe alterations of sperm ultrastructure, affecting whole sperm population, were detected in carriers of Y-deletions. Our data confirms the highest frequency of Y deletions in azoospermic patients. In all other patients with Y microdeletions, sperm ultrastructural defects affected the whole sperm population and were mainly related to apoptosis or immaturity. PMID- 17283967 TI - Cells of embryonic and regenerating germinal layers within barb ridges: implication for the development, evolution and diversification of feathers. AB - The formation of feathers occurs by the transformation of the embryonic epidermis of feather filaments into keratinized barbules and barbs. The present ultrastructural study directly documents this transformation in chick and zebrafinch downfeathers and juvenile feathers. The transformation of the epidermis in the feather filament (downfeathers) or in the follicle (juvenile feathers) is similar. The change in cell shape of subperiderm or subsheath cells and surrounding barb vane ridge cells derives from the re-organization of the linear embryonic epithelium into barb ridges. In the latter the stratification of the outer and inner periderm, of the subperiderm/subsheath, and of the germinal layer of the embryonic epidermis is altered. While the external layers produce the sheath and barb vane ridge cells, subperiderm/subsheath cells are displaced into barbule plates that converge medially in the ramus area of the barb ridge. Cells in the barbule plates elongate into barbule and barb cortical cells by the synthesis of longitudinally oriented feather keratin bundles. In the mid-central area of the barb ridge (the ramus area) cells become polygonal and pile up. The external cells accumulate numerous keratin filaments forming cortical cells and are in contact with barbule cells. The above process also occurs in barb ridges of juvenile feathers and of adult feathers before molting. However, barb ridges produced within follicles of juveniles and adult feathers are longer than in downfeathers, and possess long rami. The incorporation of tritiated histidine in barbule and barb cortical cells has been studied by ultrastructural autoradiography. Most of the labeling is cytoplasmic or is associated with bundles of keratin but is not concentrated over keratin. This indicates that together with keratin possible histidine-rich keratin-associated proteins are produced during the elongation from subperiderm/subsheath to barbule/barb cells. Barb cortical cells merge with medullary cells of the ramus area. The latter accumulate lipids and few keratin bundles before degenerating into empty cells. Separation between barbule and barb cortical cells derives from the degeneration of barb vane ridge cells while separation between barb ridges derives from degeneration of cylindrical cells of marginal plates. These supportive cells incorporate less tritiated histidine than barbule/barb cells and their periderm granules are unlabelled with tritiated histidine. This indicates both that supportive cells are metabolically less active than feather-producing cells, and that putative histidine-rich proteins are only present in cells synthesizing feather keratin. Based on the morphogenesis of barb ridges a hypothesis on the evolution of downfeathers and pennaceous feathers is presented. From conical scales, thin hairy-like filaments were produced in which barb ridges were formed. The evolution of barb ridge morphogenesis with no fusion among barb ridges initially produced naked or branched barb-feathers (plumulaceous). After the formation of a follicle, the modulation of barb ridges patterning and their fusion into the rachis produced all the phenotypes of pennaceous feathers, including those later selected for flight. PMID- 17283968 TI - MUBPy is a novel centrosome-associated protein and interacts with gamma-tubulin. AB - mUBPy is a deubiquitinating enzyme expressed preferentially in male germ cells and neurons. Recently, mUBPy has been shown to be involved in the down-regulation of growth factor receptors. In mouse spermatozoa mUBPy interacts with the sperm specific molecular chaperone MSJ-1 and associates with the proteasome. The ubiquitin/proteasome system plays a key role during spermatogenesis to yield functional spermatozoa. Immunoelectron microscopy has been here used to localize both mUBPy and MSJ-1 in mouse spermatozoa. mUBPy and MSJ-1 label the cytoplasmic side of the acrosomal membrane and the centrosome, two sperm structures fundamental for a successful fertilization. In vitro protein interaction assay reveals that mUBPy is able to bind gamma-tubulin, a centrosomal protein marker. This protein interaction has been confirmed in vivo by double protein immunolabelling in spermatogenic cells. Upon the grounds of these findings and in the light of recent acquisition on the centrosome biology, we suggest that mUBPy could have a key role during mouse fertilization and propose mUBPy as a novel centrosomal component. PMID- 17283969 TI - Policy recommendations for the Nursing Workforce Head to the Legislature--a long term investment is called for. PMID- 17283970 TI - Retaining older nurses--and their knowledge--in the workforce. . . receives increased attention. PMID- 17283971 TI - ECG of the month. Exertional dyspnea with mild cyanosis and clubbing in a HIV positive woman. Diagnosis: sinus rhythm, right axis deviation, right ventricular hypertrophy. PMID- 17283972 TI - Radiology case of the month. Leg pain. Radiologic diagnosis: giant cell tumor of sacrum with aneurysmal bone cyst. PMID- 17283973 TI - Staphylococcal scalded skin syndrome: a rare complication of a common pathogen. PMID- 17283974 TI - Should we be concerned about global warming? AB - Accurate scientific predictions of the true human health outcomes of global climate change are significantly confounded by several effect modifiers that cannot be adjusted for analytically. Nevertheless, with the documented increase in average global surface temperature of 0.6 C. since 1975, there is uniform consensus in the international scientific community that the earth is warming from a variety of climatic effects, including cyclical re-warming and the cascading effects of greenhouse gas emissions to support human activities. PMID- 17283975 TI - Sterilization failures 10 to 23 years after operation. AB - A list of sterilization failures encountered on the Benign Gynecology Service, Department of Obstetrics and Gynecology, L.S.U. Medical Center, Shreveport during the last eight and one-half years of the decade of the 1990's is reported. A total of 127 failures were collected. Eighteen (14%) of these cases fulfilled the criteria of long-term sterilization failure, i.e., failure occurring 10 or more years after surgery. The range of the 18 surgical failures spanned 10 to 23 years. Thus, a significant number of sterilization failures occurred beyond the two and one-half to ten-year range which evidence-based medicine reports. PMID- 17283978 TI - Catalytic asymmetric inverse-electron-demand Diels-Alder reaction of N-sulfonyl-1 aza-1,3-dienes. PMID- 17283977 TI - Occipito-atlantal dislocation: an uncommon case of cervical spine injury. AB - Occipito-atlantal dislocation (OAD) is a rare but often lethal type of spinal injury that can be found in up to 35% of traffic fatalities. Improved pre hospital care, diagnosis, and immobilization of these patients have led to an increase in reported cases of survivors. Significant ligamentous disruption in OAD results in craniocervical instability. While the vast majority of patients will not survive, those who do present with a wide variety of neurological findings ranging from no deficit to quadriparesis with cranial nerve palsies. When the appropriate landmarks can be identified OAD can be identified on plain lateral cervical spine radiographs by using the basion-axial interval and basion dental interval (or BAI-BDI) method. When this measurement is normal, but prevertebral soft tissue swelling is present, additional imaging such as magnetic resonance imaging and computerized tomography are useful to aid in making the diagnosis. Once this is established, immobilization followed by occipitocervical fusion is recommended. We present a case of a patient who survived for a brief period of time after being hit by a vehicle and who was found to have OAD. We discuss the pathophysiology, imaging, clinical findings, and treatment for this type of spinal injury. PMID- 17283976 TI - Tuberculosis infection presenting as brain abscess in an immunocompromised host. AB - Despite advances in modern treatment, tuberculosis remains an ever-present problem. With the HIV epidemic, the prevalence of tuberculosis has risen. Contributing to this trend has been the development of multi-resistant tuberculosis strains, as well as rising immigration from nations where tuberculosis is endemic. Although tuberculosis most commonly manifests as a pulmonary process, milary tuberculosis is also on the rise. Neurotuberculosis, a rare but dangerous progression of pulmonary tuberculosis, remains a difficult diagnostic and treatment dilemma to practitioners both in the United States and abroad. We describe an unusual presentation of neurotuberculosis infection in a previously asymptomatic patient. Early recognition and treatment of intracranial tuberculosis is important if mortality is to be prevented. PMID- 17283980 TI - Highly enantioselective Friedel-Crafts reaction of indoles with imines by a chiral phosphoric acid. PMID- 17283979 TI - A highly efficient and selective route to isomeric cyclic diazadienes. PMID- 17283981 TI - Electroformation of giant vesicles on a non-electroconductive substrate. PMID- 17283982 TI - Rhodium-catalyzed asymmetric cyclodimerization of oxa- and azabicyclic alkenes. PMID- 17283983 TI - Iron porphyrin-catalyzed olefination of ketenes with diazoacetate for the enantioselective synthesis of allenes. PMID- 17283984 TI - Stereospecific interaction between immune cells and chiral surfaces. PMID- 17283985 TI - Chiral oxazaborolidine-aluminum bromide complexes are unusually powerful and effective catalysts for enantioselective Diels-Alder reactions. PMID- 17283986 TI - A selective fluorescent sensor for imaging Cd2+ in living cells. PMID- 17283987 TI - A G-quadruplex ligand with 10000-fold selectivity over duplex DNA. PMID- 17283988 TI - Probing secondary, tertiary, and quaternary structure along with protein-cofactor interactions for a helical transmembrane protein complex through 1H spin diffusion with MAS NMR spectroscopy. PMID- 17283989 TI - Quantitative evaluation of the relative cell permeability of peptoids and peptides. PMID- 17283990 TI - Myriad planar hexacoordinate carbon molecules inviting synthesis. PMID- 17283991 TI - CVD synthesis of single-walled carbon nanotubes from gold nanoparticle catalysts. PMID- 17283992 TI - Bioinspired chemical inversion of L-amino acids to D-amino acids. PMID- 17283993 TI - Enantioselective synthesis of planar-chiral metacyclophanes through rhodium catalyzed alkyne cyclotrimerization. PMID- 17283994 TI - Fluorescent core-shell Ag@SiO2 nanocomposites for metal-enhanced fluorescence and single nanoparticle sensing platforms. PMID- 17283995 TI - Direct identification of the minority and majority species in the single-molecule magnet Mn12-acetate by inelastic neutron scattering. PMID- 17283996 TI - Soft-landing isolation of Multidecker V2(benzene)3 complexes in an organic monolayer matrix: an infrared spectroscopy and thermal desorption study. PMID- 17283997 TI - Observation of the solvent shell reorganization around photoexcited atomic solutes by picosecond X-ray absorption spectroscopy. PMID- 17283998 TI - High-resolution structure of a beta-peptide bundle. PMID- 17284000 TI - Asymmetric organocatalytic beta-hydroxylation of alpha,beta-unsaturated aldehydes. PMID- 17283999 TI - Synthesis of silica hollow nanoparticles templated by polymeric micelle with core shell-corona structure. PMID- 17284001 TI - Secondary structures of peptides and proteins via NMR chemical-shielding anisotropy (CSA) parameters. AB - Complete nuclear magnetic resonance (NMR) chemical-shielding tensors, sigma, have been computed at different levels of density-functional theory (DFT), within the gauge-including atomic orbital (GIAO) formalism, for the atoms of the peptide model For-L-Ala-NH2 as a function of the backbone dihedral angles phi and psi by employing a dense grid of 10 degrees. A complete set of rigorously orthogonal symmetric tensor invariants, {sigma iso, rho, tau}, is introduced, where sigma iso is the usual isotropic chemical shielding, while the newly introduced rho and tau parameters describe the magnitude and the orientation/shape of the chemical shielding anisotropy (CSA), respectively. The set {sigma iso, rho, tau} is unaffected by unitary transformations of the symmetric part of the shielding tensor. The mathematically and physically motivated {rho, tau} anisotropy pair is easily connected to more traditional shielding anisotropy measures, like span (Omega) and skew (kappa). The effectiveness of the different partitions of the CSA information in predicting conformations of peptides and proteins has been tested throughout the Ramachandran space by generating theoretical NMR anisotropy surfaces for our For-L-Ala-NH2 model. The CSA surfaces, including Omega(phi, psi), kappa(phi, psi), rho(phi, psi), and tau(phi, psi) are highly structured. Individually, none of these surfaces is able to distinguish unequivocally between the alpha-helix and beta-strand secondary structural types of proteins. However, two- and three-dimensional correlated plots, including Omega versus kappa, rho versus tau, and sigma iso versus rho versus tau, especially for 13Calpha, have considerable promise in distinguishing among all four of the major secondary structural elements. PMID- 17284002 TI - Solution-phase structural characterization of supramolecular assemblies by molecular diffraction. AB - Structures of four molecular squares based on rhenium coordination chemistry have been characterized in the solution phase using pair distribution function (PDF) analyses of wide-angle X-ray scattering measured to better than 1 A spatial resolution. In this report we have focused, in particular, on a comparison of structures for pyrazine- and bipyridine-edged squares measured in solution with structures determined for these molecules in the solid state using X-ray crystallography and models derived from geometry optimization and molecular dynamics simulations using a classical force field. The wide-angle scattering for these assemblies is dominated by pair correlations involving one or more rhenium atoms, with both edge and diagonal Re-Re interactions appearing prominently in PDF plots. The pyrazine square is characterized by a relatively rigid structure in solution, with PDF peak positions and linewidths corresponding closely to those calculated from crystal structure data. For the bipyridine-edged square, the experimental PDF peaks measured along the molecular sides match the positions and linewidths of the PDF peaks calculated from static models. In contrast, PDF peaks measured across the diagonal distances of the molecular square deviate significantly from those calculated from the static crystallographic and energy minimized models. The experimental data are instead indicative of configurational broadening of the diagonal distances. In this respect, molecular dynamics simulations point to the importance of butterfly type motions that modulate the Re-Re diagonal distance. Indeed, the experimental data are reasonably well fit by assuming a bimodal distribution of butterfly conformers differing by approximately 25 degrees in the Re-Re-Re-Re torsion angle. Additionally, the measurements provide evidence for solvent ordering by the supramolecular assemblies detected as regions of solvent association and exclusion. PMID- 17284004 TI - Intermolecular covalent pi-pi bonding interaction indicated by bond distances, energy bands, and magnetism in biphenalenyl biradicaloid molecular crystal. AB - Density-functional theory (DFT) calculations were performed for energy band structure and geometry optimizations on the stepped pi-chain, the isolated molecule and (di)cations of the chain, and various related molecules of a neutral biphenalenyl biradicaloid (BPBR) organic semiconductor 2. The dependence of the geometries on crystal packing provides indirect evidence for the intermolecular covalent pi-pi bonding interaction through space between neighboring pi-stacked phenalenyl units along the chain. The two phenalenyl electrons on each molecule, occupying the singly occupied molecular orbitals (SOMOs), are participating in the intermolecular covalent pi-pi bonding making them partially localized on the phenalenyl units and less available for intramolecular delocalization. The band structure shows a relatively large bandwidth and small band gap indicative of good pi-pi overlap and delocalization between neighboring pi-stacked phenalenyl units. A new interpretation is presented for the magnetism of the stepped pi chain of 2 using an alternating Heisenberg chain model, which is consistent with DFT total energy calculations for 2 and prevails against the previous interpretation using a Bleaney-Bowers dimer model. The obtained transfer integrals and the magnetic exchange parameters fit well into the framework of a Hubbard model. All presented analyses on molecular geometries, energy bands, and magnetism provide a coherent picture for 2 pointing toward an alternating chain with significant intermolecular through-space covalent pi-pi bonding interactions in the molecular crystal. Surprisingly, both the intermolecular transfer integrals and exchange parameters are larger than the intramolecular through-bond values indicating the effectiveness of the intermolecular overlap of the phenalenyl SOMO electrons. PMID- 17284005 TI - Observation of a small number of molecules at a metal nanogap arrayed on a solid surface using surface-enhanced Raman scattering. AB - In situ Raman spectroscopic measurements with 785 nm excitation were carried out in aqueous solutions containing bipyridine derivatives. Intense Raman signals were observed when the Ag dimer structure was optimized. The SERS activity was dependent upon on the structure of the Ag dimer with a distinct gap distance, suggesting that the intense SERS originates from the gap part of the dimer. Characteristic time-dependent spectral changes were observed. Not only a spectrum which was the superposition of two bipyridine spectra but also spectra which can be assigned to one of the bipyridine derivatives were frequently observed. Observation using solutions with different concentrations proved that the spectra originated from very small numbers of molecules at the active SERS site of the dimer. PMID- 17284003 TI - Structural dynamics of the cooperative binding of organic molecules in the human cytochrome P450 3A4. AB - Cytochrome P450 3A4 (CYP3A4) is a key enzyme responsible for the metabolism of 50% of all orally administered drugs which exhibit an intriguing kinetic behavior typified by a sigmoidal dependence of the reaction velocity on the substrate concentration. There is evidence for the binding of two substrates in the active site of the enzyme, but the mechanism of this cooperative binding is unclear. Diazepam is such a drug that undergoes metabolism by CYP3A4 with sigmoidal dependence. Metabolism is initiated by hydrogen atom abstraction from the drug. To understand the factors that determine the cooperative binding and the juxtaposition of the C-H bond undergoing abstraction, we carried out molecular dynamics simulations for two enzymatic conformers and examined the differences between the substrate-free and the bound enzymes, with one and two diazepam molecules. Our results indicate that the effector substrate interacts both with the active substrate and with the enzyme, and that this interaction results in side chain reorientation with relatively minor long-range effects. In accord with experiment, we find that F304, in the interface between the active and effector binding sites, is a key residue in the mechanism of cooperative binding. The addition of the effector substrate stabilizes F304 and its environment, especially F213, and induces a favorable orientation of the active substrate, leading to a short distance between the targeted hydrogen for abstraction and the active species of the enzyme. In addition, in one conformer of the enzyme, residue R212 may strongly interact with F304 and counteract the effector's impact on the enzyme. PMID- 17284008 TI - TiIV-mediated reactions between primary amines and secondary carboxamides: amidine formation versus transamidation. AB - Titanium(IV)-mediated reactions between primary amines and secondary carboxamides exhibit different outcomes, amidine formation versus transamidation, depending on the identity of the TiIV complex used and the reaction conditions employed. The present study probes the origin of this divergent behavior. We find that stoichiometric TiIV, either Cp*TiIV complexes or Ti(NMe2)4, promotes formation of amidine and oxotitanium products. Under catalytic conditions, however, the outcome depends on the identity of the TiIV complex. Competitive amidine formation and transamidation are observed with Cp*TiIV complexes, generally favoring amidine formation. In contrast, the use of catalytic Ti(NMe2)4 (< or =20 mol %) results in highly selective transamidation. The ability of TiIV to avoid irreversible formation of oxotitanium products under the latter conditions has important implications for the use of TiIV in catalytic reactions. PMID- 17284007 TI - Symmetry control of radiative decay in linear polyenes: low barriers for isomerization in the S1 state of hexadecaheptaene. AB - The room temperature absorption and emission spectra of the 4-cis and all-trans isomers of 2,4,6,8,10,12,14-hexadecaheptaene are almost identical, exhibiting the characteristic dual emissions S1-->S0 (21Ag- --> 11Ag-) and S2-->S0 (11Bu+ --> 11Ag-) noted in previous studies of intermediate length polyenes and carotenoids. The ratio of the S1-->S0 and S2-->S0 emission yields for the cis isomer increases by a factor of approximately 15 upon cooling to 77 K in n-pentadecane. In contrast, for the trans isomer this ratio shows a 2-fold decrease with decreasing temperature. These results suggest a low barrier for conversion between the 4-cis and all-trans isomers in the S1 state. At 77 K, the cis isomer cannot convert to the more stable all-trans isomer in the 21Ag- state, resulting in the striking increase in its S1-->S0 fluorescence. These experiments imply that the S1 states of longer polyenes have local energy minima, corresponding to a range of conformations and isomers, separated by relatively low (2-4 kcal) barriers. Steady state and time-resolved optical measurements on the S1 states in solution thus may sample a distribution of conformers and geometric isomers, even for samples represented by a single, dominant ground state structure. Complex S1 potential energy surfaces may help explain the complicated S2-->S1 relaxation kinetics of many carotenoids. The finding that fluorescence from linear polyenes is so strongly dependent on molecular symmetry requires a reevaluation of the literature on the radiative properties of all-trans polyenes and carotenoids. PMID- 17284006 TI - Screening of 5-HT1A receptor antagonists using molecularly imprinted polymers. AB - Molecular imprinting produces network polymers with recognition sites for imprint molecules. The high binding affinity and selectivity in conjunction with the polymers' physical robustness positions molecular imprinted polymers (MIPs) as candidates for use as preliminary screens in drug discovery. As such, MIPs can serve as crude mimics of native receptors. In an effort to evaluate the relationship between MIPs and native receptors, imprinted polymers for WAY 100635, an antagonist of the serotonin (5-HT) receptor subtype 5-HT1A were prepared. The resulting MIP P(WAY) was evaluated as an affinity matrix in the screening of serotonin receptor antagonists with known affinities for the native receptor. Rough correlations in affinity between the synthetic P(WAY) and native receptor 5-HT1A were found. These findings provide some support for the analogy between MIPs and native receptors and their possible use as surrogates. PMID- 17284009 TI - Sequential reduction of high hydride count octahedral rhodium clusters [Rh6(PR3)6H12][BArF4]2: redox-switchable hydrogen storage. AB - Cyclic voltammetry on the octahedral rhodium clusters with 12 bridging hydride ligands, [Rh6(PR3)6H12][BArF4]2 (R = Cy Cy-[H12]2+, R = iPr iPr-[H12]2+; [BArF4]- = [B{C6H3(CF3)2}4]-) reveals four potentially accessible redox states: [Rh6(PR3)6H12]0/1+/2+/3+. Chemical oxidation did not produce stable species, but reduction of Cy-[H12]2+ using Cr(eta6-C6H6)2 resulted in the isolation of Cy [H12]+. X-ray crystallography and electrospray mass spectrometry (ESI-MS) show this to be a monocation, while EPR and NMR measurements confirm that it is a monoradical, S = 1/2, species. Consideration of the electron population of the frontier molecular orbitals is fully consistent with this assignment. A further reduction is mediated by Co(eta5-C5H5)2. In this case the cleanest reduction was observed with the tri-isopropyl phosphine cluster, to afford neutral iPr-[H12]. X ray crystallography confirms this to be neutral, while NMR and magnetic measurements (SQUID) indicate an S =1 paramagnetic ground state. The clusters Cy [H12]+ and iPr-[H12] both take up H2 to afford Cy-[H14]+ and iPr-[H14], respectively, which have been characterized by ESI-MS, NMR spectroscopy, and UV vis spectroscopy. Inspection of the frontier molecular orbitals of S = 1 iPr [H12] suggest that addition of H2 should form a diamagnetic species, and this is the case. The possibility of "spin blocking" in this H2 uptake is also discussed. Electrochemical investigations on the previously reported Cy-[H16]2+ [J. Am. Chem. Soc. 2006, 128, 6247] show an irreversible loss of H2 on reduction, presumably from an unstable Cy-[H16]+ species. This then forms Cy-[H12]2+ on oxidation which can be recharged with H2 to form Cy-[H16]2+. We show that this loss of H2 is kinetically fast (on the millisecond time scale). Loss of H2 upon reduction has also been followed using chemical reductants and ESI-MS. This facile, reusable gain and loss of 2 equiv of H2 using a simple one-electron redox switch represents a new method of hydrogen storage. Although the overall storage capacity is very low (0.1%) the attractive conditions of room temperature and pressure, actuation by the addition of a single electron, and rapid desorption kinetics make this process of interest for future H2 storage applications. PMID- 17284010 TI - The enantiomeric scaffold approach to highly functionalized 1-oxadecalines: enantio- and regiocontrolled [4 + 2] cycloadditions of 5-alkenyl-eta3 pyranylmolybdenum complexes. AB - TpMo(CO)2(5-alkenyl-eta-2,3,4-pyranyl) diene complexes function as excellent chiral scaffolds for the efficient regio- and enantiocontrolled synthesis of highly functionalized 1-oxadecaline derivatives through a novel transition metal mediated Diels-Alder reaction. Very good to excellent yields and excellent levels of endo selectivity are obtained, and the reaction gives products with complete retention of enantiomeric purity when carried out with chiral, nonracemic scaffolds. A subtle structural modification on the diene (replacement of an H by a trans-CH3 group) leads to a complete change of regiochemistry, which is discussed from a mechanistic point of view. The role of the eta3-coordinated TpMo(CO)2 moiety is also critical to the further functionalization of the [4 + 2] cycloadducts, as illustrated by the preparation of 20 variously functionalized 1 oxadecaline derivatives (>98% ee when carried out with high enantiopurity scaffolds). PMID- 17284011 TI - Dendritic molecular transporters provide control of delivery to intracellular compartments. AB - Novel biocompatible macromolecular vectors were developed that not only enable transport of bioactive cargo across the cell membrane but also control the delivery into defined intracellular compartments. This work describes the synthesis and design of two non-peptidic fluorescently labeled Newkome-type dendrimers, differentiated over a varied alkyl spacer with guanidine end moieties. The internalization of the fluorescein-labeled molecular transporter into mammalian cells showed strong subcellular localizations, evident with both live cells and fixed cells costained with DAPI, a nuclear stain. We observed that the subcellular distribution of these vectors varied significantly, as one of the vectors concentrates in the nucleus (FD-1) while the other (FD-2) concentrates in the cytosol. All experiments performed with NIH-3T3 fibroblasts and human microvascular endothelial cells (HMEC) showed similar results. The differential localization patterns of the two molecular transporters can be controlled through the variation of alkyl spacer length at the terminal generation of the dendrimer. Intracellular delivery of bioactive entities into specific subcellular locations, utilizing this practical approach, might overcome limitations in drug delivery and pioneer future technologies in drug transport. PMID- 17284013 TI - Screening of underivatized oligosaccharides extracted from the stems of Triticum aestivum using porous graphitized carbon liquid chromatography-mass spectrometry. AB - Highly polar oligosaccharide analytes are notoriously difficult to separate by HPLC without prior derivatization or the use of highly alkaline eluent systems. Using a porous graphitic carbon (PGC) HPLC column, we have studied a pool of endogenous underivatized water-soluble oligosaccharides that were extracted from the stems of a range of wheat cultivars. The aqueous/organic eluents that are used with this stationary phase are ideal electrospray solvents and hence facilitate the on-line coupling of the analysis to mass spectrometry. Our on-line PGC-LC-MS method has allowed the separation of native oligosaccharides, dp 2-20, in under 30 min. The method is robust and suitable for the separation of other complex oligosaccharide mixtures. We propose that isomers of fructan structures are separated and that the branching in these structures can affect their elution order. Further, our findings on the size and type of oligosaccharides extracted from wheat stems have been compared to grain yield data. Cultivars known to be high in stem carbohydrate content have been shown to contain larger oligosaccharide structures than cultivars classified as low in stem carbohydrate content. Interestingly, the largest oligosaccharides were present in the stems of wheat plants harvested 14 days after flowering, which correlates directly with the time that grain filling occurs. PMID- 17284012 TI - Acceleration of microwave-assisted enzymatic digestion reactions by magnetite beads. AB - In this study, we demonstrated that microwave-assisted enzymatic digestion could be greatly accelerated by multifunctional magnetite beads. The acceleration of microwave-assisted enzymatic digestion by the presence of the magnetite beads was attributable to several features of the beads. Their capacity to absorb microwave radiation leads to rapid heating of the beads. Furthermore, their negatively charged functionalities cause adsorption of proteins with opposite charges onto their surfaces by electrostatic interactions, leading to a concentration on the surfaces of the beads of proteins present in trace amounts in the solution. The adsorbed proteins are denatured and hence rendered vulnerable to enzymatic digestion and are digested on the beads. For microwave heating, 30 s was sufficient for carrying out the tryptic digestion of cytochrome c, in the presence of magnetite beads, while 1 min was adequate for tryptic digestion of myoglobin. The digestion products were characterized by MALDI-MS. This rapid enzymatic digestion allowed the entire time for identification of proteins to be greatly reduced. Furthermore, specific proteins present in trace quantities were enriched from the sample on the magnetite beads and could be rapidly isolated from the sample by employing an external magnetic field. These multiple roles of magnetite beads, as the absorber for microwave irradiation, the concentrating probe, and the agent for unfolding proteins, contributed to their capability of accelerating microwave-assisted enzymatic digestion. We also demonstrated that trypsin immobilized magnetite beads were suitable for use in microwave-assisted enzymatic digestion. PMID- 17284014 TI - Chemical agent identification by field-based attenuated total reflectance infrared detection and solid-phase microextraction. AB - Attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy is used to identify liquid and solid-phase chemicals. This research examines the feasibility of identifying vapor-phase chemicals using a field-portable ATR-FT-IR spectrometer (TravelIR) combined with solid-phase microextraction (SPME). Two nerve agent simulants, diisopropyl methylphosphonate (DIMP) and di-methyl methylphosphonate (DMMP), and three sorbent polymers were evaluated. Each polymer was deposited as a thin film on the instrument's sampling interface to partition and concentrate the simulants from air samples prepared in Tedlar bags. The lowest vapor concentrations identified were 50 ppb (v/v) (DIMP) and 250 ppb (v/v) (DMMP). The ATR-FT-IR instrument demonstrated a linear response at concentrations of 1 ppm (v/v) and below. Increasing the sample exposure time, the sample air velocity, and the film thickness was demonstrated to increase the amount of analyte extracted from the air sample. This research demonstrates that it is feasible to use a portable ATR-FT-IR spectrometer with SPME sampling to detect and identify vapor-phase chemicals. PMID- 17284015 TI - Active site of epoxide hydrolases revisited: a noncanonical residue in potato StEH1 promotes both formation and breakdown of the alkylenzyme intermediate. AB - The carboxylate of Glu35 in the active site of potato epoxide hydrolase StEH1 interacts with the catalytic water molecule and is the first link in a chain of hydrogen bonds connecting the active site with bulk solvent. To probe its importance to catalysis, the carboxylate was replaced with an amide through an E35Q mutation. Comparing enzyme activities using the two trans-stilbene oxide (TSO) enantiomers as substrates revealed the reaction with R,R-TSO to be the one more severely affected by the E35Q mutation, as judged by determined kinetic parameters describing the pre-steady states or the steady states of the catalyzed reactions. The hydrolysis of S,S-TSO afforded by the E35Q mutant was comparable with that of the wild-type enzyme, with only a minor decrease in activity, or a change in pH dependencies of kcat, and the rate of alkylenzyme hydrolysis, k3. The pH dependence of E35Q-catalyzed hydrolysis of R,R-TSO, however, exhibited an inverted titration curve as compared to that of the wild-type enzyme, with a minimal catalytic rate at pH values where the wild-type enzyme exhibited maximum rates. To simulate the pH dependence of the E35Q mutant, a shift in the acidity of the alkylenzyme had to be invoked. The proposed decrease in the pKa of His300 in the E35Q mutant was supported by computer simulations of the active site electrostatics. Hence, Glu35 participates in activation of the Asp nucleophile, presumably by facilitating channeling of protons out of the active site, and during the hydrolysis half-reaction by orienting the catalytic water for optimal hydrogen bonding, to fine-tune the acid-base characteristics of the general base His300. PMID- 17284016 TI - Evolution of organo-cyanometallate cages: supramolecular architectures and new Cs+-specific receptors. AB - The ability of inorganic cyanometallate polymers to form interesting and useful complexes is well-known. This Account summarizes work, especially in our laboratories, aimed at replicating aspects of this inorganic chemistry in homogeneous solution using organometallic building blocks. A library of molecular organometallic cyanides and Lewis acids, with varying charges and labilities, are shown to give families of neutral and charged cages. Neutral and anionic cages, often molecular boxes, bind larger alkali metals tightly. Cubic frameworks show an unparalleled affinity for cesium cations over potassium cations. Noncubic cages are described including tetrahedranes, defect boxes, trigonal prisms, and hexagonal prisms. PMID- 17284019 TI - Studies of the kinetics and thermochemistry of the forward and reverse reaction Cl + C6H6 = HCl + C6H5. AB - The laser flash photolysis resonance fluorescence technique was used to monitor atomic Cl kinetics. Loss of Cl following photolysis of CCl4 and NaCl was used to determine k(Cl + C6H6) = 6.4 x 10(-12) exp(-18.1 kJ mol(-1)/RT) cm(3) molecule( 1) s(-1) over 578-922 K and k(Cl + C6D6) = 6.2 x 10(-12) exp(-22.8 kJ mol(-1)/RT) cm(3) molecule(-1) s(-1) over 635-922 K. Inclusion of literature data at room temperature leads to a recommendation of k(Cl + C6H6) = 6.1 x 10(-11) exp(-31.6 kJ mol(-1)/RT) cm(3) molecule(-1) s(-1) for 296-922 K. Monitoring growth of Cl during the reaction of phenyl with HCl led to k(C6H5 + HCl) = 1.14 x 10(-12) exp(+5.2 kJ mol(-1)/RT) cm(3) molecule(-1) s(-1) over 294-748 K, k(C6H5 + DCl) = 7.7 x 10(-13) exp(+4.9 kJ mol(-1)/RT) cm(3) molecule(-1) s(-1) over 292-546 K, an approximate k(C6H5 + C6H5I) = 2 x 10(-11) cm(3) molecule(-1) s(-1) over 300-750 K, and an upper limit k(Cl + C6H5I) < or = 5.3 x 10(-12) exp(+2.8 kJ mol(-1)/RT) cm(3) molecule(-1) s(-1) over 300-750 K. Confidence limits are discussed in the text. Third-law analysis of the equilibrium constant yields the bond dissociation enthalpy D(298)(C6H5-H) = 472.1 +/- 2.5 kJ mol(-1) and thus the enthalpy of formation Delta(f)H(298)(C6H5) = 337.0 +/- 2.5 kJ mol(-1). PMID- 17284020 TI - Experimental and modeling study of C5H10O2 ethyl and methyl esters. AB - Due to the world's over-reliance on fossil fuels there has been a developing interest in the production of renewable biofuels such as methyl and ethyl esters derived from vegetable oils and animal fats. To increase our understanding of the combustion chemistry of esters, the oxidation of methyl butanoate and ethyl propanoate, both with a molecular formula of C5H10O2, have been studied in a series of high-temperature shock tube experiments. Ignition delay times for a series of mixtures, of varying fuel/oxygen equivalence ratios (phi = 0.25-1.5), were measured behind reflected shock waves over the temperature range 1100-1670 K, and at pressures of 1.0, and 4.0 atm. It was found that ethyl propanoate was consistently faster to ignite than methyl butanoate, particularly at lower temperatures. Detailed chemical kinetic mechanisms have been assembled and used to simulate these experiments with good agreement observed. Rate of production analyses using the detailed mechanisms shows that the faster reactivity of ethyl propanoate can be explained by a six-centered unimolecular decomposition reaction with a relatively low activation energy barrier producing propanoic acid and ethylene. The elimination reaction itself is not responsible for the increased reactivity; it is the faster reactivity of the two products, propanoic acid and ethylene that leads to this behavior. PMID- 17284023 TI - Structural characterization and reactivity of UO2(salophen)L and [UO2(salophen)]2: dimerization of UO2(salophen) fragments in noncoordinating solvents (salophen = N,N'-disalicylidene-o-phenylenediaminate, L = N,N dimethylformamide, dimethyl sulfoxide). AB - The molecular structures of UO2(salophen)L (L = DMF, DMSO) and a uranyl-salophen complex without any unidentate ligands (L) in solid and solution were investigated using single-crystal X-ray analysis and IR, 1H NMR, and UV-visible absorption spectroscopies. As a result, it was found that the uranyl-salophen complex without L is a racemic dimeric complex, [UO2(salophen)]2, in which the UO2(salophen) fragments are held together by bridging between one of the phenoxide oxygen atoms in salophen and the uranium in the other UO2(salophen) unit. Furthermore, it was spectrophotometrically demonstrated that [UO2(salophen)]2 retains its dimeric structure even in the noncoordinating solvents such as CH2Cl2 and CHCl3 and is in equilibrium with UO2(salophen)L {2UO2(salophen)L right arrow over left arrow [UO2(salophen)]2 + 2L}. The equilibrium constants and thermodynamic parameters of this equilibrium were evaluated from UV-visible absorption and 1H NMR spectral changes; log Kdim = 2.51 +/- 0.01 for L = DMF and solvent = CH2Cl2, log Kdim = -1.68 +/- 0.02 for L = DMF and solvent = CHCl3, log Kdim = -4.23 +/- 0.01 for L = DMSO and solvent = CH2Cl2, and log Kdim = -3.03 +/- 0.02 for L = DMSO and solvent = CHCl3. The kinetics of L-exchange reactions in UO2(salophen)L and enantiomer exchange of [UO2(salophen)]2 in noncoordinating solvents were also studied using NMR line broadening method. As a consequence, it was suggested that the DMF-exchange reaction in UO2(salophen)DMF proceeds through two pathways (dissociative and associative paths) and that the predominant path of DMSO exchange in UO2(salophen)DMSO is the dissociative one. A sliding motion of the UO2(salophen) fragments was considered to be reasonable for the enantiomer-exchange mechanism of [UO2(salophen)]2. On the basis of the kinetic information for UO2(salophen)L and [UO2(salophen)]2, reaction mechanisms including the L-exchange reaction in UO2(salophen)L, the formation of [UO2(salophen)]2 from UO2(salophen)L, and the enantiomer exchange of [UO2(salophen)]2 are proposed. PMID- 17284021 TI - Conformationally constrained analogues of diacylglycerol (DAG). 27. Modulation of membrane translocation of protein kinase C (PKC) isozymes alpha and delta by diacylglycerol lactones (DAG-lactones) containing rigid-rod acyl groups. AB - Highly rigid and geometrically well-defined rods composed of ethynylene substituted aromatic spacers [oligo(p-phenyleneethynylene), OPE] were incorporated as acyl moieties on diacylglycerol lactones (DAG-lactones) and investigated for their ability to bind to protein kinase C (PKC) and translocate PKC alpha and delta isoforms to plasma and internal membranes. The kinetics of PKC translocation were correlated with biological responses, viz. ERK phosphorylation, induction of IL-6 secretion, inhibition of cell proliferation, and induction of cellular attachment, that display very different time courses. Because OPE rods assemble through noncovalent forces and form stable films, they may influence the microdomain environment around the DAG-lactone membrane-binding site. A comparison of two DAG-lactones (1 and 10), one with two PE units (1) and the other with an equivalent flexible acyl chain (10) of matching lipophilicity, clearly demonstrated the effect of the rigid OPE chain in substantially prolonging the translocated state of both PKC alpha and delta. PMID- 17284024 TI - Binuclear vanadium carbonyls: the limits of the 18-electron rule. AB - The fact that the stable mononuclear vanadium carbonyl V(CO)6 fails to satisfy the 18-electron rule has led to an investigation of the binuclear vanadium carbonyls V2(CO)n (n = 10-12) using methods from density functional theory. There are several important experimental studies of these homoleptic binuclear vanadium carbonyls. The global minimum for V2(CO)12 is a singlet structure having two V(CO)6 units linked by a long V-V single bond (3.48 A by B3LYP or 3.33 A by BP86) without any bridging CO groups. For V2(CO)11 the global minimum is a singlet structure V2(CO)10(eta2-mu-CO) with a four-electron pi-donor bridging CO group. For V2(CO)10 the global minimum is an unsymmetrical singlet (OC)4VV(CO)6 structure with three semibridging CO groups and a V-V distance of 2.54 A (B3LYP) or 2.51 A (BP86), suggesting a VV triple bond. The theoretical nu(CO) frequencies of this V2(CO)10 isomer agree approximately with those assigned by Ishikawa et al. (J. Am. Chem. Soc. 1987, 109, 6644) to a V2(CO)10 isomer produced in the photolysis of gas-phase V(CO)6. In contrast, the laboratory bridging nu(CO) frequency assigned to V2(CO)12 by Ford et al. (Inorg. Chem. 1976, 15, 1666) seems more likely to arise from the lowest-lying triplet isomer of V2(CO)11. PMID- 17284025 TI - Recognition of thymine and related nucleosides by a Zn(II)-cyclen complex bearing a ferrocenyl pendant. AB - A cyclen derivative bearing a ferrocenyl arm (L) and a series of its ZnII complexes [ZnL(OH2)][ClO4]2 (C1), [ZnL(OH)][ClO4] (C2), and [ZnL(Cl)][ClO4].CH3CN (C3) (cyclen = 1,4,7,10-tetraazacyclododecane, L = 1-(ferrocenemethyl)-1,4,7,10 tetraazacyclododecane) have been prepared and characterized spectroscopically. An X-ray structure determination confirmed the formation of complex C1 and revealed that the coordinated water participates in hydrogen bonding with the perchlorate counter ions. The pKa value for deprotonation of the water molecule determined by potentiometric titration was found to be 7.36 +/- 0.09 at 25 degrees C and I = 0.1 (KNO3). The possibility of using complex C1 as a potential sensor for thymine derivatives in aqueous solution has been examined. Shifts in the 1H and 13C NMR resonances showed the binding occurred with thymine (T) and two thymine derivatives, thymidine (dT) and thymidine 5'-monophosphate (TMP2-). Significant shifts of the nuC=O and nuC=C vibrations of the thymine derivatives were also observed via IR spectroscopy upon complexation with the receptor. The thymine adduct, [ZnL(thymine anion)][ClO4].2H2O (C4), has been crystallized and characterized. The X-ray structure of C4 confirmed the thymine binding to the receptor, and the short Zn-N(thymine) distance of 1.975(5) A indicated clearly that the ferrocenyl arm does not affect the complexation of the DNA base. In contrast to the large spectral changes, electrochemical studies showed a small shift of the reversible potential of the redox couple Fc+/Fc (Fc = ferrocene) and subtle changes in voltammetry upon the addition of an excess of dT, TMP2-, and guanine (dG) at physiological pH, indicating the level of interaction is similar in both Fc and Fc+ forms. PMID- 17284026 TI - Photochemical production of a highly reactive porphyrin-iron-oxo species. AB - Oxidation of 5,10,15,20-tetramesitylporphyrinatoiron(III) perchlorate, (TMP)FeIII(ClO4), with ferric perchlorate in acetonitrile gave a metastable species identified as (TMP)FeIV(ClO4)2 that decayed within seconds to the known isomeric species (TMP*+)FeIII(ClO4)2. Irradiation of the metastable species with 355 nm laser light gave a highly reactive transient that reacts with simple organic reductants (alkenes and arylalkanes) 5 orders of magnitude faster than known Compound I analogues, (TMP*+)FeIV(O)(X-). PMID- 17284027 TI - Homochiral coordination polymer with infinite double-stranded helices. AB - Hydrothermal reaction of 4,4-trimethylenedipyridine (tmdp) with ZnI2 under 175 degrees C yields a novel compound, {[Zn2I4(tmdp)2]n.[Zn2I4(tmdp)2]n}, which has a chiral infinite double-stranded helical structure consisting of two single stranded helices of the same handedness. PMID- 17284028 TI - Low-temperature spectral observation of the first six-coordinate nitrosyl complexes of cobalt(II) meso-tetratolylporphyrin with trans nitrogen base ligands. AB - Low-temperature interaction of nitrogen base ligands with layered Co(TTP)(NO) (TTP = meso-tetratolylporphyrinato dianion) as well as its toluene solution leads to the formation of the first six-coordinate species of the general formula (B)Co(TTP)(NO) (where B = piperidine and pyridine). The nu(NO) stretching bands of these species appear at lower frequencies compared with the five-coordinate nitrosyl derivative and depend on the nature of the trans axial ligand. The equilibrium constants and enthalpies of formation of these new species are determined. Fairly stable at low-temperature conditions in the solid state, they slowly dissociate the nitrogen base ligands upon warming to restore the five coordinate nitrosyl complex Co(TTP)(NO). PMID- 17284029 TI - Structure and thermoelectric characterization of AxBa8-xAl14Si31 (A = Sr, Eu) single crystals. AB - Single crystals of AxBa8-xAl14Si31 (A = Sr, Eu) were grown using a molten Al flux technique. Single-crystal X-ray diffraction confirms that AxBa8-xAl14Si31 (A = Sr, Eu) crystallize with the type I clathrate structure, and phase purity was determined with powder X-ray diffraction. Stoichiometry was determined to be Sr0.7Ba7.3Al14Si31 and Eu0.3Ba7.7Al14Si31 by electron microprobe analysis. These AxBa8-xAl14Si31 phases can be described as framework-deficient clathrate type I structures with the general formula, AxBa8-xAlySi42-3y/4[]4-1/4y. DSC measurements indicate that these phases melt congruently at 1413 and 1415 K for Sr0.7Ba7.3Al14Si31 and Eu0.3Ba7.7Al14Si31, respectively. Temperature-dependent resistivity indicates metallic behavior, and the negative Seebeck coefficient indicates transport processes dominated by electrons as carriers. Thermal conductivity of these phases remains low with Sr0.7Ba7.3Al14Si31 having the lowest values. PMID- 17284030 TI - Surface chemistry of aerosolized silicon nanoparticles: evolution and desorption of hydrogen from 6-nm diameter particles. AB - The surface chemistry of pristine, 6-nm silicon nanoparticles has been investigated. The particles were produced in an RF plasma and studied using a tandem differential mobility analysis apparatus, Fourier transform infrared spectroscopy (FTIR), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and transmission electron microscopy. Particles were extracted from the plasma, which operates at approximately 20 Torr, into an atmospheric pressure aerosol flow tube, and then through a variable-temperature furnace that could be adjusted between room temperature and 1200 degrees C. DMA measurements show that freshly generated silicon particles shrink with heating, with particle diameters decreasing by approximately 0.25 nm between 350 and 400 degrees C. FTIR results indicate that freshly generated particles are primarily covered with SiH2 groups and smaller amounts of SiH and SiH3. Spectra recorded as a function of heating temperature indicate that the amount of surface hydrogen, as measured by the intensity of modes associated with SiH, SiH2, and SiH3, decreases with heating. ToF-SIMS measurements also suggest that hydrogen desorbs from the particles surfaces over the same temperature range that the particles shrink. PMID- 17284031 TI - Effect of field direction on electrowetting in a nanopore. AB - We manifest a significant influence of field direction and polarity on surface wetting, when the latter is tuned by application of an external electric field. Thermodynamics of field-induced filling of hydrocarbon-like nanopores with water is studied by open ensemble molecular simulation. Increased field strength consistently results in water-filling and electrostriction in hydrophobic nanopores. A threshold field commensurate with surface charge density of about one elementary charge per 10 nm2 suffices to render prototypical paraffin surfaces hydrophilic. When a field is applied in the direction perpendicular to the confining walls, the competition between orientational polarization and angle preferences of interfacial water molecules relative to the walls results in an asymmetric wettability of opposing surfaces (Janus interface). Reduction of surface free energy observed upon alignment of confinement walls with field direction suggests a novel mechanism whereby the applied electric field can operate selectively on water-filled nanotubes while empty ones remain unaffected. PMID- 17284032 TI - Spectroscopic observation of conformation-dependent charge distribution in a molecular cation. AB - A prototypical case of a molecular radical cation is reported whose electrostatic charge distribution is determined entirely and uniquely by its conformational structures. Experimental observation of charge distribution in a molecular ion was for the first time demonstrated to be feasible by optical spectroscopy in the case of L-phenylalanine cation by utilizing the fact that its photodissociation propensity is entirely determined by the electronic character of its charge distribution. The cationic charge was explicitly shown to be localized in a single site or two different sites depending on the molecular conformation. PMID- 17284033 TI - Carbocyclization by radical closure onto O-trityl oximes: dramatic effect of diphenyl diselenide. AB - O-Trityl oximes of 5- and 6-iodoaldehydes undergo radical cyclization to produce oximes when treated in refluxing tetrahydrofuran (THF) with Bu3SnH, 1,1' azobis(cyclohexanecarbonitrile), i-Pr2NEt, and diphenyl diselenide (PhSeSePh). PMID- 17284034 TI - Layer-engineering of high-Tc superconductors: (Cu,Mo)Sr2(Ce,Y)4Cu2O13+delta with a quadruple-fluorite-layer block between CuO2 planes. AB - Among high-Tc superconductive copper oxides, there have been known phases that contain fluorite-structured layers as an additional "blocking block" between adjacent CuO2 planes. Here, we report that even a phase with the CuO2 planes separated by a 12-A thick quadruple-fluorite-layer block can be synthesized in a single phase and strongly oxygenated form to exhibit superconductivity with a Tc value as high as 55 K. The new phase is the fourth member of the (Cu,Mo)Sr2(Ce,Y)sCu2O(5+2s+delta) or (Cu,Mo)-12s2 homologous series. Comparison with the previously known s = 1, 2, and 3 members of the series reveals the amazing conclusion that Tc remains essentially unaffected upon inserting additional fluorite-structured layers between the two CuO2 planes as long as the hole-doping level of the planes is kept constant. PMID- 17284035 TI - Isotropic bicelles stabilize the functional form of a small multidrug-resistance pump for NMR structural studies. PMID- 17284036 TI - Electrochemical oxidation of water by an adsorbed mu-oxo-bridged Ru complex. PMID- 17284037 TI - Noncovalent functionalization of carbon nanotubes by fluorescein-polyethylene glycol: supramolecular conjugates with pH-dependent absorbance and fluorescence. PMID- 17284039 TI - Cyclization reaction of cyano-substituted unsaturated esters prompted by conjugate addition of organoborons. AB - [reaction: see text] Unsaturated esters possessing a pendent cyano moiety react with B-Ar-9-BBNs in the presence of a rhodium(I) catalyst to give the five- and six-membered beta-enamino esters in good yield. An (oxa-pi-allyl)rhodium(I) intermediate, formed by initial conjugate addition of an Ar-rhodium(I) species, undergoes a facile intramolecular addition to the cyano group to construct the carbocyclic skeletons. PMID- 17284038 TI - Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. PMID- 17284041 TI - Selective cleavage of allyl and propargyl ethers to alcohols catalyzed by Ti(O-i Pr)4/MXn/Mg. AB - [reaction: see text] Allyl and propargyl ethers were effectively deallylated or depropargylated to the parent alcohols via a C-O bond cleavage catalyzed by a low valent titanium reagent (LVT), Ti(O-i-Pr)4/TMSCl/Mg or Ti(O-i-Pr)4/MgBr2/Mg, under mild reaction conditions. Differentiation between the allyl and propargyl ethers was achieved by the reaction in the presence of AcOEt as an additive. The reagent also catalyzed intra- and intermolecular cyclotrimerization reactions of alkynes to substituted benzenes. PMID- 17284042 TI - Aldehyde-selective Wacker oxidation in a thiyl-mediated vinyl group transfer route to daunosamine. AB - [reaction: see text] Asymmetric dihydroxylation, thiyl radical mediated transfer of a silicon-tethered vinyl group to a hydrazone and an unconventional aldehyde selective Wacker oxidation are sequenced for an efficient synthesis of methyl N trifluoroacetyl-L-daunosaminide in 32% overall yield from crotonaldehyde. PMID- 17284040 TI - Columnar assembly formation and metal binding of cyclic tri-beta-peptides having terpyridine ligands. AB - [reaction: see text] A novel cyclic tri-beta-peptide having terpyridine (tpy) metal ligands was synthesized to investigate its assembly formation and metal complexation. Microscopic observation revealed that this cyclic peptide formed a rod-shaped molecular assembly. The assembly was able to bind Cu(II) because the tpy ligands covered the surface of the crystal, keeping the tpy plane parallel to the ring plane of the cyclic tri-beta-peptide. PMID- 17284043 TI - Short and efficient synthesis of cryptophycin unit A. AB - [reaction: see text] Two short synthetic approaches toward cryptophycin unit A comprise a catalytic asymmetric dihydroxylation as the sole source of chirality, while all further stereogenic centers are introduced under substrate control. The key step of the first route is a vinylogous Mukaiyama aldol addition, which introduces the alpha,beta-unsaturated ester moiety with defined configuration at the delta-carbon atom. Likewise, allylation with allyltributylstannane diastereoselectively gives the homoallylic alcohol that can be converted by a metathesis reaction to a unit A precursor. PMID- 17284044 TI - Synthesis of dendritic oligothiophenes and their self-association properties by intermolecular pi-pi interactions. AB - [structure: see text] The addition of oligothiophene into a dendritic structure causes a self-association behavior by intermolecular pi-pi interactions in a solution and in a solid state. Increasing the generation of the dendritic structure gives not only a high association constant but also sufficient field effect hole mobility, which indicates that the charge-transporting passes are formed by the strong pi-pi interactions. PMID- 17284045 TI - Three-component, one-pot sequential synthesis of N-aryl, N'-alkyl barbiturates. AB - [reaction: see text] Condensation between N-alkyl, N'-aryl carbodiimides and malonic acid monoesters leads to a high-yield formation of N-acyl urea derivatives that could be cyclized to C-monosubstituted barbiturates by addition of a suitable base in a one-pot sequential fashion. In the presence of an electrophile, the last step gives rise to a one-pot, three-component sequential synthesis of fully substituted barbiturates. PMID- 17284046 TI - Pd-catalyzed asymmetric allylic amination of Morita-Baylis-Hillman adduct derivatives using chiral diaminophosphine oxides: DIAPHOXs. AB - [reaction: see text] Asymmetric allylic amination of allylic carbonates prepared from racemic Morita-Baylis-Hillman adducts proceeded in the presence of Pd catalyst, chiral diaminophosphine oxide (DIAPHOX), and BSA, affording the corresponding chiral aza-Morita-Baylis-Hillman adduct derivatives in excellent yield with up to 99% ee. The cyclic reaction products could be converted into various synthetically useful compounds such as chiral cyclic beta-amino acids. PMID- 17284047 TI - Development of an axial chirality switch. AB - [reaction: see text] Switching axial chirality: The development and synthesis of a new axial chiral system, which shows solvent-dependent atropisomerism, is described. Control of axial chirality by the choice of solvent was studied by NMR and CD spectroscopy. PMID- 17284048 TI - Organocatalytic highly enantioselective nitroaldol reaction of alpha ketophosphonates and nitromethane. AB - [reaction: see text] The first organocatalytic highly enantioselective nitroaldol reaction of alpha-ketophosphonates and nitromethane has been realized by using cupreine (2) or 9-O-benzylcupreine (3) as the catalyst. Both catalysts are highly reactive and highly enantioselective. alpha-Hydroxy-beta-nitrophosphonates have been synthesized in good yields and excellent enantioselectivities (>or=90% ee) at a low catalyst loading (5 mol %). These nitroaldol products may be reduced to the biologically significant beta-amino-alpha-hydroxyphosphonates with complete retention of the stereochemistry. PMID- 17284049 TI - Improved quantitative analysis of oligosaccharides from lichenase-hydrolyzed water-soluble barley beta-glucans by high-performance anion-exchange chromatography. AB - Cereal beta-glucan is a linear biopolymer linked by beta-(1,3)/(1,4)-glycosidic bonds. More specifically, the beta-(1,4)-linked glucose chain is interrupted with beta-(1,3)-linkages in cereal beta-glucan structure. Elucidation of the exact length and distribution of linear beta-(1,4)-linked portion facilitates the understanding of the fine structure of cereal beta-glucan. A HPAEC assisted by lichenase treatment has been used for the structural and quantitative analysis of cereal beta-glucan. The absence of authentic standard oligosaccharides, putatively 3-O-beta-cellobiosyl-D-glucose (DP3) and 3-O-beta-cellotriosyl-D glucose (DP4), was a potential problem to the characterization of beta-glucan structure. In this study, two major lichenase-hydrolyzed products were generated from the barley beta-glucan, and putative 3-O-beta-cellobiosyl-D-glucose and 3-O beta-cellotriosyl-D-glucose were separated and highly purified by recycling preparative HPLC technology. Structural analysis of highly purified putative 3-O beta-cellobiosyl-D-glucose and 3-O-beta-cellotriosyl-D-glucose was performed by TLC and LC-MS analysis. Two putative DP3 and DP4 displayed the nonreducing end/(1,4)/(1,3) linkage ratios of 1:0.96:0.90 and 1:2.18:1.16, respectively; the molecular masses (m/z) of their sodium adducts were 527.0 and 689.0, respectively. Using these structurally confirmed oligosaccharides, the exact amounts of beta-glucan lichenase hydrolysates from domestic barley cultivars were quantified. The amount of two major DP3 and DP4 accounted for only 71.4-73.3% of water-extractable beta-glucan fraction, and the (1,4)/(1,3) linkage ratios of the extracted beta-glucans were almost identical in the range of 2.24-2.25 among the barley cultivars tested. PMID- 17284050 TI - Reaction pathways of the diketonitrile degradate of isoxaflutole with hypochlorite in water. AB - Isoxaflutole (IXF; Balance) belongs to a new class of isoxazole herbicides. Isoxaflutole has a very short half-life in soil and rapidly degrades to a stable and phytotoxic degradate, diketonitrile (DKN). DKN was previously discovered to rapidly react with hypochlorite (OCl-) in tap water, yielding the benzoic acid (BA) degradate as a major product, but the complete reaction pathway and mechanism have not been elucidated. Thus, the objectives of this work were to (1) determine the stoichiometry of the reaction between DKN and OCl-; (2) identify products in addition to BA; and (3) propose a complete pathway and reaction mechanism for oxidation of DKN by OCl-. Stoichiometry of the reaction showed a molar ratio of OCl-/DKN of 2. In addition, two previously uncharacterized chlorinated intermediates were identified under conditions in which OCl- was the limiting reactant. The proposed chemical structure of a chlorinated benzoyl intermediate was inferred from a series of HPLC/MS and HPLC/MS/MS experiments and the use of mass spectral simulation software. A chlorinated ketone intermediate was also identified using ion trap GC/MS. Two additional end products were also identified: cyclopropanecarboxylic acid (CPCA) and dichloroacetonitrile (DCAN). On the basis of the reaction stoichiometry, the structure of the chlorinated intermediates, and the identification of the products, two reaction pathways are proposed. Both pathways involve a two-step nucleophilic attack and oxidation of the diketone structure of DKN, leading to formation of BA, DCAN, and CPCA. PMID- 17284051 TI - Consumption of a novel dietary formula of plant sterol esters of canola oil fatty acids, in a canola oil matrix containing 1,3-diacylglycerol, reduces oxidative stress in atherosclerotic apolipoprotein E-deficient mice. AB - The antiatherogenic properties of a novel dietary formula (PS-CO) of plant sterol esters of fatty acids, produced by enzymatic interesterification of plant sterols with canola oil (CO), in a CO matrix containing 1,3-diacylglycerol, were evaluated in apolipoprotein E-deficient mice. PS-CO consumption strongly tended to lower total plasma cholesterol levels by 21%, compared to the placebo group. Blood triglycerides were reduced by 38% and 36% compared to CO and placebo-fed mice, respectively. Serum lipid peroxide levels were lowered following PS-CO administration by 62% and 63%, compared to CO and placebo administration, respectively. Unlike CO supplementation, PS-CO consumption preserved serum paraoxonase (PON1) activity. Mouse peritoneal macrophages from PS-CO-fed mice exhibited reduced cellular uptake of oxidized-LDL compared to those from placebo fed mice and demonstrated a tendency toward a decreased capability to release superoxide anions. These findings indicate that PS-CO supplementation is beneficial in reducing serum lipid levels, and serum and macrophage oxidative stress, thus contributing to the reduction in atherogenic risk factors. PMID- 17284052 TI - Radical scavenging conserves from unused fresh green tea leaves. AB - Green teas were made by inactivating the enzymes present in fresh leaves of coarse/pruned (unused) and normal (used for tea) grades using different sources of thermal energies. Green teas were extracted in a Soxhlet using different solvents. The obtained miscella was subjected to concentration to give the extract. The extract was subjected to solvent-solvent extraction. Solvent extract was concentrated to obtain conserve. The yields of conserves are 17 +/- 0.8 and 15 +/- 0.8% from green teas of normal and coarse tea leaves, respectively. The radical scavenging activity of these extracts was evaluated using a DPPH in vitro model system. The total polyphenol content was also determined and found to be higher in conserves from normal tea leaves. However, radical scavenging activity of conserves from coarse and normal green tea leaves was found to be >90% at 15 ppm concentration. The HPLC profiles of these conserves were used to quantify the total catechin content with the help of calibration curves prepared using authentic samples at known concentrations. The total catechin content is found to be in the range of 55-85%. Results indicated that the extracts from coarse leaves also possess potential biological activity and could be used as nutraceuticals as well as for preservation purposes in food formulations. PMID- 17284053 TI - Novel sulfated octa- and decasaccharides from squid cartilage chondroitin sulfate E: sequencing and application for determination of the epitope structure of the monoclonal antibody MO-225. AB - A mixture of octa- and decasaccharides obtained by the digestion with the hyaluronidase of chondroitin sulfate E derived from squid cartilage was subfractionated into 20 and 23 different components, respectively, by anion exchange HPLC. MALDI-TOF/MS was used to assign the sugar and sulfate composition of the putative octa- and decasaccharides, and a disaccharide composition analysis revealed the building blocks to be A- [GlcUAbeta1-3GalNAc(4S)], C- [GlcUAbeta1-3GalNAc(6S)], and E- [GlcUAbeta1-3GalNAc(4S,6S)] units, where 4S and 6S represent 4-O- and 6-O-sulfate, respectively. The sequences of these octa- and decasaccharides were determined at low picomole amounts by a combination of enzymatic digestions with chondroitinases in conjunction with anion-exchange HPLC. Sequencing revealed that each fraction is a mixture of a major component together with one to three minor components, reflecting the heterogeneity of the parent polysaccharide. Among the 11 different octasaccharide sequences reported here, 8 are novel, while all of the 6 decasaccharide sequences are novel, and this is the first report of the sequencing of CS oligosaccharides longer than octasaccharides. The reactivity of the monoclonal antibody MO-225 with octa- and decasaccharides tested with an oligosaccharide microarray revealed that a CS-E decasaccharide is the minimal requirement for antibody recognition. Among the 6 decasaccharides, only E-E-E-E-C was recognized by MO-225, suggesting the requirement of a C-unit at the reducing end and also the importance of chain length, which in turn may indicate the importance of the conformation acquired by this specific sequence for antibody recognition. PMID- 17284054 TI - Functional and structural interactions of the transmembrane domain X of NhaA, Na+/H+ antiporter of Escherichia coli, at physiological pH. AB - The 3D structure of Escherichia coli NhaA, determined at pH 4, provided the first structural insights into the mechanism of antiport and pH regulation of a Na+/H+ antiporter. However, because NhaA is activated at physiological pH (pH 7.0-8.5), many questions pertaining to the active state of NhaA have remained open, including the physiological role of helix X. Using a structural-based evolutionary approach in silico, we identified a segment of most conserved residues in the middle of helix X. These residues were then used as targets for functional studies at physiological pH. Cysteine-scanning mutagenesis showed that Gly303, in the middle of the conserved segment, is an essential residue and Cys replacement of Lys300 retains only Li+/H+ antiporter activity, with a 20-fold increase in the apparent KM for Li+. Cys replacements of Leu296 and Gly299 increase the apparent KM of the Na+/H+ antiporter for both Na+ and Li+. Accessibility test to N-ethylmaleimide and 2-sulfonatoethyl methanethiosulfonate showed that G299C, K300C, and G303C are accessible to the cytoplasm. Suppressor mutations and site-directed chemical cross-linking identified a functional and/or structural interaction between helix X (G295C) and helix IVp (A130C). While these results were in accordance with the acid-locked crystal structure, surprisingly, conflicting data were also obtained; E78C of helix II cross-links very efficiently with several Cys replacements of helix X, and E78K/K300E is a suppressor mutation of K300E. These results reveal that, at alkaline pH, the distance between the conserved center of helix X and E78 of helix II is drastically decreased, implying a pH-induced conformational change of one or both helices. PMID- 17284055 TI - Size distribution of superparamagnetic particles determined by magnetic sedimentation. AB - We report on the use of magnetic sedimentation as a means to determine the size distribution of dispersed magnetic particles. The particles investigated here are (i) single anionic and cationic nanoparticles of diameter D approximately 7 nm and (ii) nanoparticle clusters resulting from electrostatic complexation with polyelectrolytes and polyelectrolyte-neutral copolymers. A theoretical expression of the sedimentation concentration profiles at the steady state is proposed, and it is found to accurately describe the experimental data. When compared to dynamic light scattering, vibrating sample magnetometry, and cryogenic transmission electron microscopy, magnetic sedimentation exhibits a unique property: it provides the core size and core size distribution of nanoparticle aggregates. PMID- 17284056 TI - Enthalpy of interaction and binding isotherms of non-ionic surfactants onto micellar amphiphilic polymers (amphipols). AB - The interactions in water between short amphiphilic macromomolecules, known as amphipols, and three neutral surfactants (detergents), dodecylmaltoside (DM), n octylthioglucoside (OTG), and n-octyltetraethyleneoxide (C8E4), have been assessed by static and dynamic light-scattering (SLS and DLS), capillary electrophoresis (CE), and isothermal titration calorimetry (ITC). The amphipols selected are random copolymers of the hydrophobic n-octylacrylamide (25-30 mol %), a charged hydrophilic monomer, either acrylic acid ( approximately 35 mol %) or a phosphorylcholine-modified acrylamide (40-70 mol %), and, optionally, N isopropylacrylamide (30-40 mol %). In water, the copolymers form micelles of small size (hydrodynamic radius: approximately 5 nm). Neutral surfactants, below their critical micellar concentration (cmc), form mixed micelles with the amphipols irrespective of the chemical structure of the detergent or the polymer. The fraction of detergent in the surfactant/polymer complexes increases significantly (cooperatively) as the surfactant concentration nears the cmc. The ITC data, together with data gathered by CE, were fitted via a regular mixing model, which allowed us to predict the detergent concentration in equilibrium with complexes and the heat evolved upon transfer of detergent from water into a mixed surfactant/polymer complex. The enthalpy of transfer was found to be almost equal to the enthalpy of micellization, and the regular mixing model points to a near-ideal mixing behavior for all systems. Amphipols are promising tools in biochemistry where they are used, together with neutral surfactants, for the stabilization and handling of proteins. This study provides guidelines for the optimization of current protein purification protocols and for the formulations of surfactant/polymer systems used in pharmaceutics, cosmetics, and foodstuffs. PMID- 17284057 TI - Adhesion of biologically inspired vertical and angled polymer microfiber arrays. AB - This paper proposes an approximate adhesion model for fibrillar adhesives for developing a fibrillar adhesive design methodology and compares numerical simulation adhesion results with macroscale adhesion data from polymer microfiber array experiments. A technique for fabricating microfibers with a controlled angle is described for the first time. Polyurethane microfibers with different hardnesses, angles, and aspect ratios are fabricated using optical lithography and polymer micromolding techniques and tested with a custom tensile adhesion measurement setup. Macroscale adhesion and overall work of adhesion of the microfiber arrays are measured and compared with the models to observe the effect of fiber geometry and preload. The adhesion strength and work of adhesion behavior of short and long vertical and long angled fiber arrays have similar trends with the numerical simulations. A scheme is also proposed to aid in optimized fiber adhesive design. PMID- 17284058 TI - Intermicellar interactions may induce anomalous size behavior in micelles carrying out bulky heads with multiple spatial arrangements. AB - We report experimental and theoretical results on the concentration dependence of the micellar size of GM1 and GM1acetyl gangliosides, five-sugar-headed anionic glycolipids. Contrary to one of the mainstays of colloid science, that the aggregation number of amphiphile aggregates grows with concentration, an anomalous region is found at intermediate concentrations, where a sharp decrease of the aggregation number occurs. Experiments were performed by small-angle X-ray and neutron scattering (SAXS and SANS). Two models are discussed, reproducing the observed behavior of either GM1acetyl or GM1. The first one is a conventional picture of interacting micelles where a reduction in the molecular surface area, leading to an increase of the aggregate dimension, is paid to reduce intermicellar interactions: it foresees a monotonous increase of the aggregation number with concentration. The second one accounts for a conformational bistability of the bulky headgroups of GM1, modifying the amphiphilic molecular surface area and protrusion from the aggregate surface, and contributing to the inter- and intramicellar interaction balance. Energy minimization leads to a complex behavior of the aggregation number, which is consistent with the anomalous behavior of GM1. PMID- 17284059 TI - Stabilized gold nanoparticles by reduction using 3,4-ethylenedioxythiophene polystyrenesulfonate in aqueous solutions: nanocomposite formation, stability, and application in catalysis. AB - Herein, we report a one-pot synthesis of highly stable Au nanoparticles (AuNPs) using 3,4-ethylenedioxythiophene (EDOT) as a reductant and polystyrene sulfonate (PSS-) as a dopant for PEDOT and particle stabilizer. The synthesis demonstrated in this work entails the reduction of HAuCl4 using EDOT in the presence of PSS-. The formation of AuNPs with concomitant EDOT oxidation is followed by UV-vis spectroscopy at various time intervals. Absorption at 525 nm is due to the surface plasmon band of AuNPs (violet), and broad absorption above 700 nm is due to oxidized PEDOT that was further characterized to be in its highly oxidized (doped) state, using FT-Raman spectroscopy. Transmission electron microscopy shows a polydisperse nature of the particles, and the selected area electron diffraction pattern reveals the polycrystalline nature of AuNPs. With stabilizers such as sodium dodecylsulfate (SDS) (green) and polyvinylpyrrolidone (PVP) (blue), the absorbance around 525 nm was found to be negligibly small, while PSS- showed high absorbance at 525 nm (violet) and above 700 nm (oxidized PEDOT). PSS- also allows complete oxidation of EDOT and serves as an effective dopant for PEDOT. While AuNPs covered by PEDOT alone cannot be dispersed in aqueous solutions, PSS- renders Au-PEDOT water soluble. The hydrodynamic diameter of the nanocomposite estimated from the dynamic light scattering (DLS) measurements increases in the order Na-PSS < SDS < PVP. Interestingly, the color of the Au(nano)-PEDOT/PSS- aqueous dispersion changed reversibly between violet and blue and vice versa on addition of NaOH and HCl, respectively. This reversible color change appears to be a combination effect of acid/base on the properties of PEDOT, in turn changing the environment around the embedded AuNPs. The nanoparticle dispersion also exhibited very high stability in presence of 3.0 M NaCl. Remarkably, the nanocomposite Au(nano)-PEDOT/PSS- was found to function as an effective catalyst to activate the reduction of 4-nitrophenol to 4-aminophenol in the presence of excess NaBH4, and the calculated apparent rate constant value of 4.39 x 10-2 s-1 is found to be higher than those obtained using other nanocomposites with SDS and PVP and comparable to the values reported in the case of other encapsulants. PMID- 17284060 TI - Surface patterns induced by Cu2+ ions on BPEI/PAA layer-by-layer assembly. AB - The multilayer films of branched polyethyleneimine (BPEI) and poly(acrylic acid) (PAA) have been fabricated with the layer-by-layer (LbL) method. Two characteristic courses of the film thickness growth are observed, which are the initial exponential-like growth and the following linear growth. The variation of the COOH/COO- ratio indicates that the ionization degree of the polyelectrolyte molecules decreases at the initial stage of the multilayer buildup and then levels off after about eight bilayers. The as-prepared (BPEI/PAA)n films show a relatively smooth surface. However, great morphology changes occur after immersing these films in Cu2+ or Zn2+ solution. In the case of n > or =7, wavelike surface patterns are induced to form on the films. Both wavelength and fluctuation of these surface patterns show a systematical variation with an increase of the bilayer number. Moreover, thermal treatment can stabilize these patterns and enable the preservation of them after releasing the Cu2+ ions from the LbL films by acidic treatment. Interestingly, only Cu2+ and Zn2+ can induce the formation of such surface patterns, whereas Fe2+, Ca2+, Ag+, and Na+ cannot. This phenomenon may closely relate to the different natures of the metal ions. PMID- 17284061 TI - Cathepsin D is secreted from M-BE cells: its potential role as a biomarker of lung cancer. AB - The early diagnosis of lung cancer is an effective approach to reduce the mortality caused by malignancy. To explore serum biomarkers of lung cancer at early stage, M-BE, a SV40T-transformed human bronchial epithelial cell line with the phenotypic features of early tumorigenesis at high passage, was cultured in the conditioned media to collect its secretory proteins. The proteins secreted from different passage M-BE cells were extracted and then separated by two dimensional electrophoresis (2-DE). MALDI-TOF/TOF mass spectrometry was adopted to identify the passage-dependent 2-DE spots. Totally, 47 proteins were identified, including 23 that were up-regulated and 24 that were down-regulated. Of these proteins, cathepsin D was a typical secretory protein that exhibited the increased abundance either in culture media or in cells during passaging. Furthermore, the proteomic conclusions were validated in the clinical samples of lung cancer patients. When sandwich ELISA was used, the concentrations of cathepsin D in plasma showed significant differences between lung squamous cell carcinomas (SCC, 104 cases) and normal donors (36 cases, p H+ + A- , and (3) any follow-up chemistry, e.g., dissociation or reaction of the protonated anion, HA. This is discussed for the five different anions studied. The reduction of HNTf(2) was also studied in two [NTf(2)]- -based RTILs and was compared to the oxidation waves from hydrogen. The results have implications for the defining of pKa in RTIL media, for the development of suitable reference electrodes for use in RTILs, and in the possible amperometric sensing of H2 gas. PMID- 17284066 TI - Different thermal unfolding pathways of catalase in the presence of cationic surfactants. AB - In this paper we have corroborated the usefulness of spectroscopic techniques, such as UV-visible, in the study and thermodynamic characterization of the thermal unfolding of catalase as a function of the concentration and alkyl chain length of n-alkyltrimethylammonium bromides (CnTAB, n = 8, 10, and 12). For this reason, a thermodynamic model was used which included experimental data corresponding to the pre- and posttransition into the observable transition. It has been found that n-alkyltrimethylammonium bromides play two opposite roles in the folding and stability of catalase. They act as a structure stabilizer at a low molar concentration and as a destabilizer at a higher concentration. The maximum of the unfolding temperature has been found to decrease with the alkyl chain. The reason for this difference has been suggested to be the side chains involved. In the presence of C8TAB and C10TAB, Gibbs energies of unfolding (DeltaG(T)) decrease with concentration, whereas for C12TAB an increase has been observed. These findings can be explained by the fact that when differences in the hydrophobic nature of the surfactants exist, different pathways of unfolding may occur. Also, the presence of surfactants has been observed to affect the cold denaturation of catalase. Thermodynamic results suggest that the thermal denaturation of catalase in the presence of n-alkyltrimethylammonium bromides is a perfect transition between two states. PMID- 17284068 TI - Kinetics of induced crystallization of the LC(1-x)Sil(x) system. AB - This study explores the kinetics of a new feature, called "induced crystallization (IC)", observed in an Aerosil dispersed octylcyanobiphenyl (8CB) liquid crystal system. Heating rate dependent experiments were performed using modulation differential scanning calorimetry (MDSC) at various heating ramp rates. In the presence of Aerosil nanoparticles, a well-defined exothermic peak was found as an additional feature on the heating scan before the melting transition, which was absent in the bulk 8CB; hence, we like to call it an "IC" as it is induced by Aerosil nanoparticles in the system. The system LC1-xSilx was prepared by mixing Aerosil nanoparticles in the bulk 8CB by the solvent dispersion method (SDM) where LC represents bulk 8CB and Sil represents Aerosil nanoparticles with x as the Aerosil fraction. The concentration of the Aerosil nanoparticles (x) varied from 0 to 0.2 g/cm3 in the bulk 8CB. The IC transition peak showed a temperature shift and change in the shape and size in the presence of Aerosil nanoparticles. In addition, this transition shifted significantly with different heating ramp rates following an Arrhenius behavior showing activated kinetics. The presence of Aerosil nanoparticles caused a significant increase in the enthalpy and decrease in the activation energy for the IC transition as the density of Aerosil nanoparticles increases and showed a saturation for the highest density of Aerosil nanoparticles. This behavior can be explained in terms of molecular disorder and surface molecular interaction induced by adding Aerosil nanoparticles into the bulk of 8CB liquid crystal. PMID- 17284070 TI - Phytochemical investigation of Turnera diffusa. AB - A phytochemical investigation of Turnera diffusa afforded 35 compounds, comprised of flavonoids, terpenoids, saccharides, phenolics, and cyanogenic derivatives, including five new compounds (1-5) and a new natural product (6). These compounds were characterized as luteolin 8-C-E-propenoic acid (1), luteolin 8-C-beta-[6 deoxy-2-O-(alpha-l-rhamnopyranosyl)-xylo-hexopyranos-3-uloside] (2), apigenin 7-O (6' '-O-p-Z-coumaroyl-beta-d-glucopyranoside) (3), apigenin 7-O-(4' '-O-p-Z coumaroylglucoside) (4), syringetin 3-O-[beta-d-glucopyranosyl-(1-->6)-beta-d glucopyranoside] (5), and laricitin 3-O-[beta-d-glucopyranosyl-(1-->6)-beta-d glucopyranoside] (6). Their structures were determined by spectroscopic and chemical methods. PMID- 17284071 TI - Eremophilane-type sesquiterpene derivatives from the roots of Ligularia lapathifolia. AB - Six new highly oxygenated eremophilane-type sesquiterpene derivatives (1-6), including a norbisesquiterpene, were isolated from an extract of the roots of Ligularia lapathifolia, and their structures were elucidated by spectroscopic methods. The structure of 1 was confirmed by single-crystal X-ray crystallography. In addition, the cytotoxicity of compounds 1, 2, 3, 5, and 6 was evaluated against selected cancer cell lines, including human stomach carcinoma (MGC-803), human hepatoma (HEP-G2), and murine sarcoma (S-180) cell lines. PMID- 17284069 TI - Agrobacterium rubi(T) DSM 6772 produces a lipophilic polysaccharide capsule whose degree of acetylation is growth modulated. AB - The structure of the capsular polysaccharide produced from the type strain of Agrobacterium rubi DSM 6772 is demonstrated by means of chemical and spectroscopical methodologies. It is constituted from the quite rare monosaccharide 6-deoxy-L-talose, involved in alternating alpha-(1 --> 2) and alpha-(1 --> 3) linkages. This simple backbone is further complicated from the occurrence of O-acetyl substituents located always at O-2 of the O-3 substituted 6-deoxy-talose. This decoration is not stoichiometric and it depends on the growth stadium of the bacterium, leading to an almost regular acetylation pattern only at the stationary phase, where all the potential positions are substituted. PMID- 17284072 TI - Myriaporones 1-4, cytotoxic metabolites from the Mediterranean bryozoan Myriapora truncata. AB - Four novel polyketide-derived metabolites, myriaporones 1, 2, 3, and 4, have been isolated from the Mediterranean bryozoan Myriapora truncata. Their structures and stereochemistry have been assigned from the analysis of spectroscopic data. The inseparable equilibrium mixture of myriaporones 3 and 4 showed 88% inhibition of L1210 murine leukemia cells at 0.2 microg/mL. PMID- 17284073 TI - Structural characterization of daptomycin analogues A21978C1-3(d-Asn11) produced by a recombinant Streptomyces roseosporus strain. AB - Three daptomycin-related lipopeptides, A21978C1-3(d-Asn11) (2-4), were purified from the fermentation broth of a recombinant Streptomyces roseosporus strain. Their chemical structures were determined by analyses of the biosynthetic pathway, chemical transformations, d,l-amino acid quantitation by enantiomer labeling, tandem LC-MS/MS, and 2D-NMR techniques. Compounds 2-4 exhibited potent antibacterial activity against Staphylococcus aureus with MIC values of 0.6, 0.3, and 0.15 microM, respectively, well correlated to the acyl tail chain length. PMID- 17284074 TI - Kolokosides A-D: triterpenoid glycosides from a Hawaiian isolate of Xylaria sp. AB - Four new triterpenoid glycosides, kolokosides A-D (1-4), along with the known compound 19,20-epoxycytochalasin N, were isolated from cultures of a Hawaiian wood-decay fungus (Xylaria sp.). The structures and relative configurations of 1 4 were determined primarily by analysis of NMR data, and the absolute configuration of 1 was assigned by application of the exciton chirality method. Compound 1 exhibited activity against Gram-positive bacteria. PMID- 17284076 TI - Directed ortho metalation-boronation and Suzuki-Miyaura cross coupling of pyridine derivatives: a one-pot protocol to substituted azabiaryls. AB - A general method for the synthesis of azabiaryls 19a-t by a one-pot procedure involving a Directed ortho metalation (DoM)-boronation-Suzuki-Miyaura cross coupling sequence is described. Aside from the three isomeric pyridyl carboxamides 15a-c, chloro-, fluoro-, and O-carbamoyl pyridines are adapted to this method providing a range of azabiaryls (Table 2). The method has an advantage in that it avoids the recognized difficult isolation of pyridyl boronic acids and their instability toward deboronation. The efficient synthesis of hydroxypicolinamides 12-14 (Scheme 3) by a one-pot metalation-boronation oxidation sequence with the LDA-B(OiPr)3 in situ procedure that avoids self condensation of incipient ortho-metalated species (Scheme 2) is delineated. The conversion of azabiaryls 19b,e,h,l into azafluorenones 20b,e,h,l by a directed remote metalation protocol is demonstrated (Table 3). A comprehensive survey of pyridyl boronates, of considerable interest in contemporary heterocyclic synthetic chemistry, is given (Figure 1). PMID- 17284077 TI - Convenient access to functionalized vinylcyclopentenols from alkynyloxiranes. AB - Beta,gamma-alkynyl aldehydes, generated in situ by treatment of alkynyloxiranes with a catalytic amount of Sc(OTf)3 or BF3.OEt2, are effectively trapped by a variety of allyl nucleophiles to afford homopropargylic homoallylic alcohols in good yield and selectivity. Such products are used as substrates for the synthesis of functionalized vinylcyclopentenols via enyne metathesis. PMID- 17284078 TI - A new synthesis of lysophosphatidylcholines and related derivatives. Use of p toluenesulfonate for hydroxyl group protection. AB - A new stereoselective synthesis of lysophosphatidylcholines is reported. The synthesis is based upon (1) the use of 3-p-toluenesulfonyl-sn-glycerol to provide the stereocenter for construction of the optically active lysophospholipid molecule, (2) tetrahydropyranylation of the secondary alcohol function to achieve orthogonal protection of the sn-2- and sn-3-glycerol positions, and (3) elaboration of the phosphodiester headgroup using a 2-chloro-1,3,2 dioxaphospholane/trimethylamine sequence. In the course of developing the synthesis it has been discovered that methoxyacetate displacement of the sn-3-p toluenesulfonate yields a reactive methoxyacetyl ester, which in turn can be selectively cleaved with methanol/tert-butylamine, while the ester group at the sn-1-position remains unaffected. The sequence has been shown to be suitable for preparation of spectroscopically labeled lysophosphatidylcholines. One of these compounds was readily converted to a double-labeled mixed-chain phosphatidylcholine applicable for real-time fluorescence resonance energy transfer (FRET) assay of lipolytic enzymes. In addition, the work led to new synthetic strategies based on chemoselective manipulation of the tosyl group in the presence of other base-labile groups such as FMOC derivatives that are often used for the protection of amino and hydroxyl groups in syntheses. PMID- 17284080 TI - Diversity-oriented synthetic approach to naturally abundant S-amino acid based benzannulated enantiomerically pure medium ring heterocyclic scaffolds employing inter- and intramolecular mitsunobu reactions. AB - The diversity-oriented organic synthesis of enantiomerically pure benzannulated oxazepine, diazepine, thiazepine, oxazocine, and diazocine scaffolds is described from easily accessible naturally occurring S-amino acids as chiral synthons. Inter- and intramolecular Mitsunobu reactions for the formation of carbon nitrogen, carbon-oxygen, and carbon-sulfur bonds have been used as key transformations to construct these biologically important privileged heterocycles. This is the first example where the Mitsunobu approach has been utilized for the construction of S-amino acid based seven- and eight-membered ring systems. PMID- 17284081 TI - Microwave-assisted rapid synthesis of 2,6,9-substituted purines. PMID- 17284082 TI - Clinical and therapeutic issues for herpes simplex virus-2 and HIV co-infection. AB - A synergy between HIV type-1 (HIV-1) and herpes simplex virus-2 (HSV-2) has been demonstrated in many epidemiological and clinical studies over the last decade. HIV-1 infection exacerbates the clinical impact and frequency of HSV-2 reactivation events; furthermore, HSV-2 infection exacerbates the risk of HIV acquisition and transmission and may accentuate HIV disease progression. In order to maximise the impact of existing and future therapeutic and preventive interventions, this article reviews the epidemiological, clinical and therapeutic considerations associated with episodic treatment and suppression of HSV-2 infection in HIV-infected individuals.Specifically, this article describes the current expanding epidemics of both HIV and HSV-2, and how high rates of asymptomatic herpes virus shedding contribute to the under-diagnosis and continued spread of both HSV-2 and HIV. Furthermore, multiple clinical trials have studied the efficacy and clinical utility of aciclovir and other nucleoside analogues for treating and suppressing HSV-2. We review these studies and summarise the guidelines for these regimens, particularly noting the accumulated experience documenting the utility of herpes treatment and suppression in altering the natural history of symptoms and documenting the low rate of HSV-2 drug resistance to nucleoside analogues observed after more that a decade of use. Finally, there are now also growing data describing the benefits of herpes suppression in the context of individuals co-infected with HIV/HSV-2, with additional clinical trials poised to further elucidate these issues in the near future. PMID- 17284083 TI - Guidelines and recommendations for the management of anaemia in patients with lymphoid malignancies. AB - Patients with lymphoid malignancies frequently require repetitive and intensive anticancer treatments to induce and maintain disease remission. Anaemia (haemoglobin [Hb] <12 g/dL) is a common and debilitating problem associated with both the malignancy itself and its treatment burden. Anaemia negatively impacts on all aspects of patient quality of life (QOL) and treatment outcomes and survival, particularly in this disease setting. Widely acknowledged goals of anaemia treatment include Hb correction to approximately 12 g/dL, reduction in transfusion requirements and optimisation of patient QOL. Since the introduction of recombinant human erythropoietic therapy, transfusion (once the only anaemia treatment option available) is now primarily reserved for non-responders or those with severe or life-threatening anaemia. Data from randomised, double-blind, placebo-controlled studies, and large, non-randomised, open-label, community based studies, along with almost 15 years of practical experience, support the assertion that epoetin alfa administered at a dosage of 150-300 U/kg three times weekly or 40,000-60,000U once weekly, both of which are US FDA-approved dose administration schedules, can effectively and safely achieve anaemia treatment goals for the majority of patients with lymphoid malignancies. Data and practical experience collected over the last 5 years on another erythropoietic agent with a slightly longer half-life but lower binding affinity, darbepoetin alfa, show that this agent when administered according to the FDA-approved dose administration schedules (2.25-4.5 microg/kg once weekly or 500microg once every 3 weeks) or according to a commonly-administered dose in clinical practice (3.0-5.0 microg/kg once every 2 weeks) can also effectively and safely correct anaemia, reduce transfusion requirements and improve QOL in many patients with lymphoid malignancies. One comparative head-to-head trial suggested that epoetin alfa might be superior to darbepoetin alfa in anaemic cancer patients receiving chemotherapy with respect to timing and magnitude of Hb correction, although further study is necessary, especially concerning optimal dose administration. Alternative dose administration schedules, such as epoetin alfa 80,000U every 2 weeks from initiation or 80,000U every 3 weeks following initiation with once weekly administration and darbepoetin alfa 4.5 microg/kg every 3 weeks following initiation with once weekly administration, are being actively investigated with the goal of increased flexibility for patients and healthcare providers. The treatment of anaemia in patients with lymphoid malignancies is an important part of overall disease management, as evidenced by continuous investigation of existing erythropoietic agents and new agents. Although treatment guidelines issued by organisations such as the National Comprehensive Cancer Network (NCCN) and American Society of Hematology (ASH)/American Society of Clinical Oncology (ASCO) suggest intervention with erythropoietic therapy when Hb falls below 10-11 g/dL or based on clinical symptoms, data suggest that anaemia is vastly under recognised and under-treated. Clearly, an update on the definition, identification and optimal management of anaemia in patients with lymphoid malignancies is warranted. PMID- 17284084 TI - Optimising antimicrobial therapy in diabetic foot infections. AB - Foot infections are common and the most serious lower extremity complication contributing to amputations, particularly in patients with diabetes mellitus. Infection is most often a consequence of foot ulcerations, which typically follows trauma to a neuropathic foot. Foot infections may be classified as mild, moderate and severe; this largely determines the approach to therapy. Gram positive bacteria are the sole causative pathogens for most mild and moderate infections. These infections can usually be treated with culture-based narrow spectrum antibacterials along with appropriate surgical debridement in an outpatient setting. In contrast, severe infections are often polymicrobial, requiring hospitalisation and treatment with broad-spectrum antibacterials along with appropriate medical and surgical interventions. The initial empirical antibacterial regimen may be tailored based on the results of culture and sensitivity tests from properly obtained specimens. Several antibacterial regimens have demonstrated effectiveness in randomised controlled trials, but no single regimen has shown superiority. Managing diabetic foot osteomyelitis is particularly controversial and requires reliable cultures to select an appropriate antibacterial regimen. Surgical resection of the infected and necrotic bone favours a good outcome in chronic osteomyelitis. The recommended duration of antibacterial therapy ranges from 1 to 4 weeks for soft tissue infection, to >6 weeks for unresected osteomyelitis. The incidence of meticillin resistant Staphylococcus aureus infection is increasing in both the healthcare setting and the community. This should be considered when selecting an antibacterial, especially if the patient does not improve with initial antibacterial therapy. Certain other organisms, such as Pseudomonas aeruginosa and Enterococcus spp., while potentially pathogenic, are often colonisers that do not require targeted therapy. PMID- 17284087 TI - Selegiline transdermal system: in the treatment of major depressive disorder. AB - The monamine oxidase (MAO) inhibitor selegiline is selective for MAO-B at the low oral dosages used in the treatment of Parkinson's disease. However, MAO-A is also inhibited at the high oral dosages needed to effectively treat depression (not an approved indication), necessitating a tyramine-restricted diet. The selegiline transdermal system was designed to deliver antidepressant drug concentrations to the CNS, without substantially impairing small intestine MAO-A activity. At the target dose of 6 mg/24 hours, tyramine dietary restrictions are not needed. Short term treatment with fixed (6 mg/24 hours) or flexible (6, 9 or 12 mg/24 hours) doses of selegiline transdermal system was superior to placebo on most measures of antidepressant activity in 6- or 8-week, randomised, double-blind, multicentre studies in adult outpatients with major depressive disorder (MDD). Likewise, long term treatment with a fixed dose of selegiline transdermal system 6 mg/24 hours was superior to placebo as maintenance therapy in a 52-week, randomised, double blind, multicentre, relapse-prevention trial in patients with MDD. Selegiline transdermal system therapy was generally well tolerated in placebo-controlled studies; application site reactions, mostly of mild to moderate severity, were the most commonly reported adverse events. The incidence of sexual adverse effects and weight gain was low and similar to that with placebo. PMID- 17284090 TI - Voriconazole : a review of its use in the management of invasive fungal infections. AB - Voriconazole (VFEND), a synthetic second-generation, broad-spectrum triazole derivative of fluconazole, inhibits the cytochrome P450 (CYP)-dependent enzyme 14 alpha-sterol demethylase, thereby disrupting the cell membrane and halting fungal growth. In the US, intravenous and/or oral voriconazole is recommended in adults for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, disseminated infections caused by Candida spp., oesophageal candidiasis, and in patients with scedosporiosis and fusariosis who are refractory to or intolerant of other antifungal therapy. In Europe, intravenous and/or oral voriconazole is recommended in adults and paediatric patients of at least 2 years of age for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, fluconazole-resistant serious invasive Candida spp. infections, scedosporiosis and fusariosis. In large randomised trials, voriconazole was an effective and generally well tolerated primary treatment for candidiasis and invasive aspergillosis in adults and adolescents. More limited data also support the use of voriconazole for the treatment of invasive fungal infections in children, in those with rare fungal infections, such as Fusarium spp. or Scedosporium spp., and in those refractory to or intolerant of other standard antifungal therapies. The availability of both parenteral and oral formulations and the almost complete absorption of the drug after oral administration provide for ease of use and potential cost savings, and ensure that therapeutic plasma concentrations are maintained when switching from intravenous to oral therapy. On the other hand, the numerous drug interactions associated with voriconazole may limit its usefulness in some patients. Further clinical experience will help to more fully determine the position of voriconazole in relation to other licensed antifungal agents. In the meantime, voriconazole is a valuable emerging option for the treatment of invasive aspergillosis and rare fungal infections, including Fusarium spp. and Scedosporium spp. infections, and provides an alternative option for the treatment of candidiasis, particularly where the causative organism is inherently resistant to other licensed antifungal agents. PMID- 17284091 TI - Imatinib: a review of its use in chronic myeloid leukaemia. AB - Imatinib (Gleevec, Glivec) is a synthetic tyrosine kinase inhibitor used in the treatment of chronic myeloid leukaemia (CML). It is specifically designed to inhibit the breakpoint cluster region (BCR)-Abelson (ABL) fusion protein that results from the chromosomal abnormality known as the Philadelphia chromosome. CML is characterised by this abnormality, which leads to abnormalities of the peripheral blood and bone marrow including an increase in the number of granular leukocytes. Imatinib is approved in numerous countries worldwide for the treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase CML, Ph+ accelerated-phase or blast-crisis CML, and in patients with Ph+ chronic phase CML who have failed to respond to interferon-alpha therapy. It is also indicated in paediatric patients with newly diagnosed Ph+ chronic-phase CML, in accelerated-phase or blast-crisis CML, or in chronic-phase CML after failure of interferon-alpha therapy or when the disease has recurred after haematopoietic stem cell transplantation (HSCT). Approved indications, however, may vary by country. Imatinib is effective and generally well tolerated in patients with Ph+ CML. In patients with newly diagnosed chronic-phase CML, imatinib was more effective than interferon-alpha plus cytarabine in preventing progression of the disease and in achieving haematological and cytogenetic responses. Overall survival rates remain high after 5 years of follow-up, and historical comparisons with other treatments demonstrate improved overall survival with imatinib in the long term. Patients with accelerated-phase or blast-crisis CML, or those who have not responded to prior interferon-alpha therapy also benefit from imatinib treatment. Some patients become resistant or intolerant to imatinib therapy; management strategies to overcome these problems include dosage adjustment, other treatments, or combination therapy with imatinib and other agents. Allogeneic HSCT is currently the only potentially curative treatment, but it is associated with high rates of morbidity and mortality and is not suitable for all patients. The introduction of imatinib has had a marked impact on outcomes in patients with CML. It remains a valuable treatment for all stages of the disease, especially initial treatment of newly diagnosed Ph+ chronic-phase CML, and is endorsed by European and US treatment guidelines as a first-line option. PMID- 17284085 TI - Treatment approaches for painful bladder syndrome/interstitial cystitis. AB - Painful bladder syndrome/interstitial cystitis (PBS/IC) is a disease of unknown aetiology, characterised by severe pressure and pain in the bladder area or lower pelvis that is frequently or typically relieved by voiding, along with urgency or frequency of urination in the absence of urinary tract infections. PBS/IC occurs primarily in women, is increasingly recognised in young adults, and may affect as many as 0.1-1% of adult women. PBS/IC is often comorbid with allergies, endometriosis, fibromyalgia, irritable bowel syndrome and panic syndrome, all of which are worsened by stress. As a result, patients may visit as many as five physicians, including family practitioners, internists, gynaecologists, urologists and pain specialists, leading to confusion and frustration. There is no curative treatment; intravesical dimethyl sulfoxide, as well as oral amitriptyline, pentosan polysulfate and hydroxyzine have variable results, with success more likely when these drugs are given together. Pilot clinical trials suggest that the flavonoid quercetin may be helpful. Lack of early diagnosis and treatment can affect outcomes and leads to the development of hyperalgesia/allodynia. PMID- 17284086 TI - The clinical applications of fluorouracil in ophthalmic practice. AB - Fluorouracil (5-fluorouracil, 5-FU) is a pyrimidine analogue that was originally known for its widespread use as an anticancer drug. The ability of 5-FU to reduce fibroblastic proliferation and subsequent scarring has made it an important adjunct in ocular and periorbital surgeries. It is used in primary glaucoma filtering surgeries and in reviving failing filtering blebs, in dacryocystorhinostomy, pterygium surgery, and in vitreoretinal surgery to prevent proliferative vitreoretinopathy. In addition, 5-FU is also gaining recognition in the treatment and surgical management of ocular surface malignancies like ocular surface squamous neoplasia; however, the specific action of the drug on highly proliferating cells limits its use in primary acquired melanosis of the conjunctiva. When applied topically, this drug has a low rate of sight threatening adverse effects, is inexpensive, and is easy to administer, making it an important tool in enhancing the success rate in ophthalmic surgery and in reducing the recurrence of ocular surface neoplasia. PMID- 17284092 TI - Treatment strategies after a single seizure : rationale for immediate versus deferred treatment. AB - What is the rationale for the treatment of an epileptic seizure? More specifically, should a first seizure be treated as soon as it is diagnosed or should one defer treatment until a second seizure occurs? Several studies indicate that the risk of a second (unprovoked) seizure is <50%, but studies vary in methodology and most have reviewed outcome in children only. Also, many patients were maintained on antiepileptic drugs (AEDs) during these studies, meaning that the risk for seizure recurrence was perhaps underestimated compared with the risk if untreated. Most neurologists recommend waiting for a second seizure in order to avoid complications of medications that might prove to be unnecessary. Several large studies show that delaying treatment until a second seizure occurs does not worsen the course of epilepsy or likelihood of eventual seizure control. Seizures attributable to an acute illness ('acute symptomatic', provoked seizures) usually resolve with treatment of the underlying illness and thus long-term AEDs are often unwarranted. Nevertheless, seizures arising in certain circumstances are more likely to recur and there are special considerations for patients with strokes, tumours, infections and dementia, and also after head injury or neurosurgery. Patient preferences with regard to risk and benefit also enter into the decision on whether to initiate AED treatment after a single seizure. PMID- 17284093 TI - Pharmacological treatment of the psychosis of Alzheimer's disease: what is the best approach? AB - Psychosis of Alzheimer's disease (PAD) forms part of the behavioural and psychological symptoms of dementia (BPSD). PAD includes symptoms of psychosis such as hallucinations or delusions, and may be associated with agitation, negative symptoms or depression. Even though the US FDA has not approved any medication for the treatment of PAD, atypical antipsychotics have been widely used and favoured by geriatric experts in the management of the condition in view of their modest efficacy and relative safety. However, the recent FDA warnings regarding the cardiac, metabolic, cerebrovascular and mortality risks associated with the use of these drugs in elderly patients with dementia have caused serious concerns regarding their use. Nevertheless, until an effective and safe medication is approved by the regulatory agencies for PAD, clinicians do not have a better choice than atypical antipsychotics for the management of the serious symptoms of this condition. PMID- 17284094 TI - Monitoring the safe use of clozapine: a consensus view from Victoria, Australia. AB - Clozapine is an important antipsychotic agent that has a unique profile of clinical benefits, but that has also been associated with several serious and potentially life-threatening safety concerns. In order to minimise the impact of haematological adverse events, health professionals treating patients with clozapine are currently required to register their patients on a centrally administered data network and to conform to strict protocols. The consensus statement documented in this article extends existing protocols by recommending monitoring of patients treated with clozapine for additional adverse effects during treatment. This consensus statement reflects the current practice at five major public psychiatric hospitals in Victoria, Australia, for the monitoring and management of clozapine-related adverse events, and has been implemented at these sites because of emerging safety concerns associating clozapine with cardiovascular and metabolic adverse effects. PMID- 17284097 TI - Spectral frequency index monitoring during propofol-remifentanil and propofol alfentanil total intravenous anaesthesia. AB - BACKGROUND: The aim of this study was to evaluate the usefulness of spectral frequency index (SFx) monitoring to assess the depth of anaesthesia during propofol-opioid total intravenous anaesthesia (TIVA). METHODS: Thirty-three patients scheduled for laparoscopic cholecystectomy under propofol TIVA were prospectively and randomly allocated to receive either remifentanil (bolus of 1.0 microg/kg, followed by continuous infusion from 0.25 to 0.05 microg/kg/min) [n = 18] or alfentanil (bolus of 10 microg/kg, followed by continuous infusion from 2.0 to 0.5 microg/kg/min) [n = 15]. EEG activity was monitored to achieve the desired depth of anaesthesia, and intravenous propofol was titrated to keep the SFx at 70-80%. The remifentanil and alfentanil groups were compared in relation to the plasma propofol concentration required for an adequate level of hypnosis during maintenance of anaesthesia, Pearson correlation coefficient for the relationship between the plasma propofol concentration and SFx values, recovery parameters, and recall of events during anaesthesia. RESULTS: The study groups were comparable with regard to demographic characteristics, type and duration of surgery, and time to resumption of spontaneous ventilation. No evidence of explicit recall was noted. The mean plasma propofol concentration required for an adequate level of hypnosis during maintenance of anaesthesia was significantly higher in the alfentanil group (3.20 microg/mL) compared with the remifentanil group (2.17 microg/L) [p < 0.05]. In both groups, the Pearson correlation coefficient test showed a linear correlation between SFx values and propofol concentration in the studied propofol concentration range. The mean time to orientation for name and place was significantly shorter (p < 0.05), the mean propofol concentration at orientation for name and place and at the resumption of spontaneous ventilation timepoints was significantly lower (both p < 0.01), and the mean SFx value at resumption of spontaneous ventilation timepoint was significantly higher (p < 0.01) in the remifentanil group. CONCLUSIONS: As SFx is linearly related to plasma propofol concentration, this index may be used to measure anaesthetic effect during propofol anaesthesia. The results of this clinical trial are consistent with a previous computer-simulated opioid-propofol model with regard to intraoperative and recovery variables, although the recovery occurred at different propofol concentration and SFx values. PMID- 17284095 TI - Lack of insight in schizophrenia: impact on treatment adherence. AB - People with schizophrenia commonly lack insight, that is, they are unaware of their illness and the consequences thereof. One of the most important consequences of lack of insight is a failure to recognise the need for treatment, leading to treatment nonadherence. With several scales that now enable objective measurement of insight, it is possible to examine correlates of insight change, including course of illness and treatment adherence. Specific interventions, both pharmacological and psychotherapeutic, have been developed to enhance illness insight and treatment adherence. The extent to which second-generation antipsychotic medications, including a recently released long-acting formulation, improve insight and/or enhance treatment adherence remains to be determined. PMID- 17284098 TI - Spotlight on methylphenidate controlled-delivery capsules (Equasym XL, Metadate CD) in the treatment of children and adolescents with attention-deficit hyperactivity disorder. AB - Controlled-delivery methylphenidate (methylphenidate CD) [Equasym XL, Metadate CD], an oral stimulant, is approved in the US and EU to treat children aged > or = 6 years who have been diagnosed with attention-deficit hyperactivity disorder (ADHD). Once-daily methylphenidate CD is generally well tolerated and effective in the treatment of children and adolescents with ADHD. Methylphenidate CD resulted in superior control of ADHD symptoms compared with osmotic release oral system (OROS) methylphenidate over a time period corresponding to that of an average school day in a laboratory classroom. In 3-week clinical trials conducted in a community setting, methylphenidate CD was superior to placebo and non inferior to methylphenidate immediate-release in the treatment of children and adolescents with ADHD. Thus, methylphenidate CD should be considered an important primary treatment on its own or in addition to behavioural and psychosocial interventions, for when a reduction in ADHD symptoms is required during the school day in preference to the evening. PMID- 17284096 TI - Various pharmacogenetic aspects of antiepileptic drug therapy: a review. AB - Pharmacogenetics concerns the influence of an individual's genetic background on the pharmacokinetics and pharmacodynamics of xenobiotics. Much of the pharmacogenetic data in the field of epilepsy deals with the pharmacokinetics of antiepileptic drugs (AEDs). In particular, two polymorphisms of cytochrome P450 2C9 are known to slow down the metabolism of phenytoin to a degree that increases the risk of the neurotoxic adverse effects of this drug among carriers of these polymorphisms. A significant number of patients with epilepsy do not respond to AEDs and such pharmacoresistance is a major, largely unsolved, problem that is likely to be multifactorial in nature. In this regard, genetic factors may influence transmembrane drug transporter proteins, thereby modifying the intracerebral penetration of AEDs. Monogenic idiopathic epilepsies are rare and frequently associated with ion channel mutations; however, to date, a consistent relationship between changes in channel properties and clinical phenotype has not been established nor has any association between genotype and response to specific treatment options. Polymorphisms of drug targets may represent another genetic facet in epilepsy: a recent study demonstrated for the first time a polymorphism of a drug target (the alpha-subunit of a voltage-gated sodium channel) associated in clinical practice with differing response to two classic AEDs. Adverse drug reactions and teratogenicity of AEDs remain a major concern. Whole-genome single nucleotide polymorphism profiling might in the future help to determine genetic predisposing factors for adverse drug reactions. Recently, in Han Chinese treated with carbamazepine and presenting with Stevens-Johnson syndrome, a strong association was found with HLA B*1502. If genetically targeted drug development becomes more affordable/cost efficient in the near future, the development of new drugs for relatively rare diseases could become economically viable for the pharmaceutical industry. The synergy of lower trial costs and efficacy-based prescribing may reduce the cost of medical treatment for a particular disease. This hypothetical advantage of the practical use of pharmacogenetics is, however, counterbalanced by several possible dangers, including illicit data mining and the development of a human 'genetic underclass' with the risk of exclusion from, for example employment or health insurance, because of an 'unfavourable' genetic profile. PMID- 17284099 TI - Iatrogenic Trichuris suis infection. PMID- 17284100 TI - The "Helsinki criteria" for attribution of lung cancer to asbestos exposure: how robust are the criteria? PMID- 17284101 TI - Detection of clonal IGH gene rearrangements: summary of molecular oncology surveys of the College of American Pathologists. AB - CONTEXT: The diagnosis of B-cell lymphoid malignancy can frequently be substantiated by detecting clonal immunoglobulin heavy chain (IGH) gene rearrangements, which is typically done by polymerase chain reaction (PCR) amplification and/or Southern blot analysis. OBJECTIVE: To characterize current laboratory practice for the assessment of IGH rearrangements and to identify opportunities for improvement. DESIGN: The data from the Molecular Oncology Proficiency Survey distributed to participating laboratories by the Molecular Pathology Committee of the College of American Pathologists from 1998 through 2003 were analyzed. RESULTS: Thirty-nine proficiency survey specimens (29 positive and 10 negative for clonal IGH rearrangements) were distributed. For Southern blot analysis, 944 results were reported, with a successful response rate of 95%. For PCR detection, 2349 results were reported, with a successful response rate of 72%. A higher rate of successful responses by PCR was achieved using framework 3 primers in combination with other frameworks (82%) compared with framework 3 primers only (76%) and when fresh/frozen (72%) compared with paraffin-embedded (65%) tissues were analyzed. CONCLUSIONS: The performance of the participating laboratories was very good, by both Southern blot and PCR analysis. As expected, Southern blot analysis consistently detects a higher proportion of IGH rearrangements than PCR analysis. Further improvement and standardization of the IGH PCR assay is important if it is to replace Southern blot analysis as the standard method. Participation in this survey is a valuable tool for assessing laboratory performance and it directs our attention to areas where we may improve laboratory practice. PMID- 17284107 TI - Mixed glioneuronal tumors: recently described entities. AB - CONTEXT: Several distinctive mixed glioneuronal tumors that warrant recognition as clinicopathologic entities have been recently described by neuropathologists. OBJECTIVE: To summarize important clinical, radiologic, and pathologic findings for 3 novel glioneuronal tumors (papillary glioneuronal tumor, rosetted glioneuronal tumor, and rosette-forming glioneuronal tumor of the fourth ventricle). DATA SOURCES: Recent reports in the pathology literature and the authors' experience with mixed glioneuronal tumors at a major cancer center. CONCLUSIONS: Histologic features enabling recognition of these recently described glioneuronal tumors are presented along with remarks concerning the classification of mixed neuronal and glial tumors exhibiting unconventional appearances. PMID- 17284104 TI - Epithelioid and epithelial neoplasms of bone. AB - CONTEXT: Epithelioid and epithelial neoplasms seen in bone are rare and include epithelioid variants of vascular lesions, osteoblastoma, osteosarcoma, chordoma, and chondroblastoma as well as adamantinoma and metastatic carcinoma. OBJECTIVE: To provide an overview of tumors with epithelioid histology and address the clinical context and diagnostic issues. DATA SOURCES: Pertinent literature is reviewed with emphasis on recent and controversial issues. CONCLUSIONS: The differential diagnosis in epithelioid/epithelial lesions of bone is limited. The primary consideration in many cases is distinguishing primary from metastatic lesions. PMID- 17284103 TI - Small round cell tumors of bone. AB - CONTEXT: Primary small round cell tumors of the bone are a heterogeneous group of malignant neoplasms presenting predominantly in children and adolescents. They include Ewing sarcoma/peripheral neuroectodermal tumor or Ewing family tumors, lymphoma, mesenchymal chondrosarcoma, and small cell osteosarcoma. Even though they share many morphological similarities, their unique biological and genetic characteristics have provided substantial insights into the pathology of these diverse neoplasms. OBJECTIVE: To provide an overview of the clinical, radiologic, pathologic, and genetic characteristics of these tumors along with a pertinent review of the literature. DATA SOURCES: A literature search using PubMed and Ovid MEDLINE was performed, and data were obtained from various articles pertaining to clinicopathologic, biological, and genetic findings in these tumors. Additionally, findings from rare cases have been included from author's subspecialty experience. CONCLUSION: The diagnosis of small round cell tumors can be made accurately by applying clinicopathologic criteria, as well as a panel of immunohistochemical and genetic studies in appropriate cases. Molecular genetic studies may provide further insight into the biology, histogenesis, and prognosis of these tumors. PMID- 17284105 TI - An overview of the histology of skeletal substitute materials. AB - CONTEXT: Orthopedic and spine surgeons are in frequent need of bone for skeletal reconstruction. The amount of autograft is limited, and conventional allograft has some disadvantages, so surgeons are now using increasing amounts of demineralized allograft and a variety of synthetic materials to replace or "extend" autograft. OBJECTIVE: To provide an overview of the composition and histology of the materials most likely to be seen by pathologists today. DATA SOURCES: The review is based on published literature and the author's experience with preclinical studies and human biopsies. CONCLUSIONS: Pathologists are likely to find these skeletal substitute materials in biopsy and resection specimens from patients who have undergone prior treatment, and recognizing a synthetic bone substitute can help explain an otherwise confusing specimen. Pathologists also play an important role in helping define the safety and efficacy of new bioactive materials. PMID- 17284108 TI - New immunohistochemical markers in the evaluation of central nervous system tumors: a review of 7 selected adult and pediatric brain tumors. AB - CONTEXT: Immunohistochemistry (IHC) has become an important tool in the diagnosis of brain tumors. OBJECTIVE: To review the latest advances in IHC in the diagnostic neuro-oncologic pathology. DATA SOURCES: Original research and review articles and the authors' personal experiences. DATA SYNTHESIS: We review the features of new, useful or potentially applicable marker antibodies as well as the new uses of already established antibodies in the area of diagnostic neuro oncologic pathology, focusing on the use of IHC for differential diagnosis and prognosis. We discuss (1) placental alkaline phosphatase, c-Kit, and OCT4 for germinoma, (2) alpha-inhibin and D2-40 for capillary hemangioblastoma, (3) phosphohistone-H3 (PHH3), MIB-1/Ki-67, and claudin-1 for meningioma, (4) PHH3, MIB-1/Ki-67, and p53 for astrocytoma, (5) synaptophysin, microtubule-associated protein 2, neurofilament protein, and neuronal nuclei for medulloblastoma, (6) INI1 for atypical teratoid/rhabdoid tumor, and (7) epithelial membrane antigen for ependymoma. All the markers presented here are used mainly for supporting or confirming the diagnosis, with the exception of the proliferation markers (MIB 1/Ki-67 and PHH3), which are primarily used to support grading and are reportedly associated with prognosis in certain categories of brain tumors. CONCLUSIONS: Although conventional hematoxylin-eosin staining is the mainstay for pathologic diagnosis, IHC has played a major role in differential diagnosis and in improving diagnostic accuracy not only in general surgical pathology but also in neuro oncologic pathology. The judicious use of a panel of selected immunostains is unquestionably helpful in diagnostically challenging cases. In addition, IHC is also of great help in predicting the prognosis for certain brain tumors. PMID- 17284110 TI - Current techniques used for the radiologic assessment of intracranial neoplasms. AB - CONTEXT: Radiologic studies are obtained for diagnostic and treatment planning purposes in the evaluation of patients with intracranial neoplasms. These studies are discussed at radiology/pathology working conferences and are often beneficial in the analysis of pathologic specimens for tissue diagnosis. Therefore, clinical pathologists should be aware of the current and evolving imaging techniques that are used in the radiologic assessment of intracranial neoplasms. OBJECTIVE: To describe the imaging techniques used in the assessment of intracranial neoplasms and provide current references. DATA SOURCES: We searched PubMed for articles published between 1995 and 2006 and also reviewed several textbooks on intracranial neoplasms, to prepare a discussion of basic modalities such as computed tomography (CT) and magnetic resonance (MR) imaging as well as advanced imaging techniques such as CT and MR angiography and venography, CT and MR perfusion, MR spectroscopy, functional MR imaging, and positron emission tomography. CONCLUSIONS: Knowledge of currently used imaging techniques for the assessment of intracranial neoplasms will assist the clinical pathologist in communications with neuroradiologists, surgeons, and referring clinicians. This review will also aid the pathologist in understanding the new and rapidly evolving imaging techniques that will likely become the standard of care in the future. PMID- 17284109 TI - Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma. AB - CONTEXT: Significant interobserver variability exists with respect to the diagnosis of oligodendroglial neoplasms, especially their distinction from astrocytoma and mixed oligoastrocytoma. Combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 has been shown to be both relatively specific to oligodendroglioma and, when present, a marker of improved prognosis in patients with these tumors. In addition, 1p/19q loss has been shown to be a marker of "classic" oligodendroglial histology. These findings raise questions as to the role of 1p/19q testing in clinical practice, both as a prognostic marker and as a potential diagnostic marker among infiltrating glial neoplasms. OBJECTIVE: This review discusses the issues raised above and tries to clarify the current status of 1p/19q evaluation in the diagnosis of oligodendroglioma. DATA SOURCES: Sources for this review include recent literature as well as the experience of 3 practicing neuropathologists. CONCLUSIONS: 1p/19q status is an important marker in oligodendroglioma. Loss of 1p/19q is associated with classic oligodendroglioma histology as well as improved prognosis. The combined 1p/19q marker will continue to be a clinically useful marker of prognosis and could potentially be incorporated into diagnostic criteria in the future. PMID- 17284111 TI - Prognostic significance of CD44, platelet-derived growth factor receptor alpha, and cyclooxygenase 2 expression in renal cell carcinoma. AB - CONTEXT: Pathologic stage is the main prognostic factor for predicting outcome in renal cell carcinoma (RCC). Because of its unreliability in predicting tumor progression, other factors are needed to provide additional prognostic information. OBJECTIVE: The expression of CD44, cyclooxygenase 2, and platelet derived growth factor receptor alpha (PDGFR-alpha) was evaluated as a potential prognostic factor for survival in patients with RCC. DESIGN: Sixty-two patients (42 men and 20 women; median age, 61 years), undergoing partial (10 cases) or radical (55 cases) nephrectomy for RCC were retrospectively analyzed by immunohistochemical analysis for CD44, cyclooxygenase 2, and PDGFR-alpha expression. Impact of various factors on disease-specific and overall survival was calculated using Cox proportional hazards models. RESULTS: There was a gradual increase in CD44 and cyclooxygenase 2 expression with increasing RCC nuclear grade. In contrast, PDGFR-alpha expression showed no consistent relationship with nuclear grade. On univariate analysis, metastasis at time of surgery (P < .001), tumor size (P = .004), pathologic stage group (P = .001), and nuclear grade (P = .004) were correlated with disease-specific survival. On multivariate analysis, only the presence of metastasis at diagnosis (P < .001) was significant. For overall survival, metastasis (P < .001), tumor size (P = .02), pathologic stage group (P = .01), nuclear grade (P = .003), and PDGFR-alpha (P = .03) were significant on univariate analysis. Only metastasis (P = .001) and PDGFR-alpha (P = .03) were significant on multivariate analysis. CONCLUSIONS: When combined with other variables, PDGFR-alpha expression in RCC may provide additional predictive value related to the patient's overall survival. However, CD44 and cyclooxygenase 2 do not seem to be independent prognostic indicators in predicting outcomes for patients with RCC. PMID- 17284112 TI - Relevance of the autopsy as a medical tool: a large database of physician attitudes. AB - CONTEXT: Autopsy rates for patients dying in hospitals have declined from approximately 50% in the 1950s to 5% or less today. OBJECTIVE: To investigate the nature of physician attitudes about autopsy in a large and varied population and to relate these attitudes to certain physician demographic variables. DESIGN: A 10-question, anonymous, multiple-choice format questionnaire was distributed to all attending physicians at 4 hospitals: 2 that were university-affiliated (1 private and 1 public), 1 military, and 1 private nonuniversity-affiliated medical center. A total of 2608 surveys were distributed. RESULTS: Three hundred eighty eight (15%) physicians responded to the survey. Respondents agreed (77%) that autopsy results could affect their future medical practice, and disagreed (73%) that the accuracy of modern diagnostic procedures makes autopsy unnecessary. Most respondents (72%) disagreed that litigation concerns play a role in the decision to request autopsy. Spearman correlation coefficients found 9 significant relationships among the survey items, with many correlations reflecting statistically significant relationships between demographic and attitudinal variables. CONCLUSIONS: The survey data and statistical analysis confirm that respondents value the autopsy as a relevant clinical tool, in spite of declining requests. One of the most crucial factors influencing attitudes is the physician's level of experience with autopsy in training and practice. Among other interesting results was that strength of belief in autopsy relevancy correlates significantly (P = .003) with greater prior exposure to the autopsy. In a sense, the current low autopsy rates may be self-perpetuating because of the paucity of and decreasing experience with autopsy by succeeding generations of clinicians. PMID- 17284113 TI - Overexpression of CD24: association with invasiveness in urothelial carcinoma of the bladder. AB - CONTEXT: CD24, originally described as a B-cell marker, has gained considerable attention in tumor research. High rates of CD24 expression have been found in several types of carcinomas that are significantly associated with a more aggressive course of the disease. To our knowledge, the expression of CD24 in urothelial carcinoma (UC) of the bladder has not been previously reported. OBJECTIVE: To determine the expression of CD24 in UCs and the association between CD24 levels and tumor grade and stage. DESIGN: Urothelial carcinomas (48 cystectomy, 87 transurethral biopsy), including 56 pTa, 29 pT1, 19 pT2, and 31 pT3, were analyzed immunohistochemically using an anti-CD24 monoclonal antibody. The intensity of CD24 staining was semiquantitatively scored as high-level or low level expression. RESULTS: In normal urothelium, CD24 was localized to the cytoplasm of the luminal cell layer with very low intensity. CD24 expression was upregulated in noninvasive UCs, and a high level of expression was correlated with the tumor grade (P = .003). Invasive UCs demonstrated strong diffuse cytoplasmic overexpression of CD24 and the difference in CD24 expression between invasive and noninvasive UC was statistically significant (P < .001). CONCLUSIONS: CD24 protein is overexpressed in a significant number of bladder UCs. The high level of CD24 expression with loss of apical localization is a marker for stromal invasion and high tumor grade in UC. This study provides the basis for future investigations of CD24 as a potential serum marker or target of antibody-based therapeutics in bladder UC. PMID- 17284114 TI - Follicular lymphoma in staging bone marrow specimens: correlation of histologic findings with the results of flow cytometry immunophenotypic analysis. AB - CONTEXT: Bone marrow (BM) examination is part of the staging workup of lymphoma patients. Few studies have compared BM histologic findings with results of flow cytometric immunophenotyping analysis in follicular lymphoma (FL) patients. OBJECTIVE: To correlate histologic findings with immunophenotypic data in staging BM biopsy and aspiration specimens of FL patients. DESIGN: Bone marrow biopsy specimens of untreated FL patients were reviewed. Histologic findings were correlated with 3-color flow cytometric immunophenotyping results on corresponding BM aspirates. RESULTS: Bone marrow biopsy specimens (with or without aspirates) of 114 patients with histologic evidence of FL in BM were reviewed. There were 76 bilateral and 38 unilateral biopsies performed, resulting in 190 specimens: 187 involved by FL and 3 negative (in patients with a positive contralateral specimen). The extent of BM involvement was < 5% in 32 (17.1%), > or = 5% and < or = 25% in 102 (54.6%), > 25% and < or = 50% in 27 (14.4%), and > 50% in 26 (13.9%) specimens. The pattern of involvement was purely paratrabecular in 81 (43.3%), mixed in 80 (42.8%), and purely nonparatrabecular in 26 (13.9%). Immunophenotyping was only performed unilaterally, on BM aspirates of 92 patients, and was positive for a monoclonal B-cell population in 53 (57.6%) patients. Immunophenotyping was more often negative when biopsy specimens showed FL with a purely paratrabecular pattern. For comparison, we assessed 163 FL patients without histologic evidence of FL in BM also analyzed by flow cytometric immunophenotyping. A monoclonal B-cell population was identified in 5 patients (3%). CONCLUSIONS: Our data suggest that 3-color flow cytometric immunophenotyping adds little information to the evaluation of staging BM specimens of FL patients. PMID- 17284115 TI - Cytokeratin and epithelial membrane antigen expression in angiosarcomas: an immunohistochemical study of 33 cases. AB - CONTEXT: Expression of epithelial cell markers can occur in mesenchymal tumors and has been reported in angiosarcomas with variable frequency. In these situations, establishing the diagnosis becomes problematic. OBJECTIVE: To determine the expression of cytokeratin and epithelial membrane antigen in angiosarcoma. DESIGN: To address this issue, 33 well-documented cases of angiosarcomas were retrieved from the archival material of Shands Hospital at the University of Florida, Gainesville, and Jackson Memorial Hospital at the University of Miami, Miami, Florida. These cases were all reviewed and studied using a cytokeratin cocktail (CAM 5.2 and AE1/AE3) and epithelial membrane antigen using standard immunohistochemical techniques. All 33 cases had available material for cytokeratin analysis; however, only 20 cases had enough material for epithelial membrane antigen staining. RESULTS: In the 33 cases studied, the age range of the patients was 2 to 88 years (mean, 63 years). There were 23 (70%) men and 10 (30%) women. One (3%) of 33 was cytokeratin-immunoreactive and 2 (10%) of 20 were epithelial membrane antigen-immunoreactive. CONCLUSION: Cytokeratin and epithelial membrane antigen immunoreactivity in angiosarcomas is infrequent but may be encountered. Interpretation of such expression should be done with caution and in conjunction with the characteristic clinical and morphologic features of the tumor as well as the expression of endothelial cell antigens. PMID- 17284116 TI - Effects of a pneumatic tube system on routine and novel hematology and coagulation parameters in healthy volunteers. AB - CONTEXT: Technologic advances affecting analyzers used in clinical laboratories have changed the methods used to obtain many laboratory measurements, and many novel parameters are now available. The effects of specimen transport through a pneumatic tube system on laboratory results obtained with such modern instruments are unclear. OBJECTIVE: To determine the effects of sample transport through a pneumatic tube system on routine and novel hematology and coagulation parameters obtained on state-of-the-art analyzers. DESIGN: Paired blood samples from 33 healthy volunteers were either hand delivered to the clinical laboratory or transported through a pneumatic tube system. RESULTS: No statistically significant differences were observed for routine complete blood cell count and white cell differential parameters or markers of platelet activation, such as the mean platelet component, or of red cell fragmentation. When 2 donors who reported aspirin intake were excluded from the analysis, there was a statistically, but not clinically, significant impact of transport through the pneumatic tube system on the mean platelet component. There were no statistically significant differences for prothrombin time, activated partial thromboplastin time, waveform slopes for prothrombin time or activated partial thromboplastin time, fibrinogen, or fibrin monomers. CONCLUSIONS: Although further study regarding the mean platelet component may be required, transport through a pneumatic tube system has no clinically significant effect on hematology and coagulation results obtained with certain modern instruments in blood samples from healthy volunteers. PMID- 17284117 TI - Malakoplakia outside the urinary tract. AB - CONTEXT: Malakoplakia is a rare granulomatous disease that occurs commonly in the urinary tract. Histologically, it is defined by sheets of histiocytes (Hansemann cells) with accumulation of granular basophilic periodic acid-Schiff-positive, diastase-resistant inclusions and calcified Michaelis-Gutmann bodies, which are pathognomonic but not necessary for diagnosis. In addition to the urinary tract, malakoplakia has been reported in other organs, including the gastrointestinal tract, central nervous system, female genital tract, and the tongue. OBJECTIVES: To review the literature of reported sites of malakoplakia outside the urinary tract and their variable clinical presentations, and to discuss the main diagnostic features and differential diagnoses of malakoplakia. The pathogenesis and possible etiologic factors are also presented. DATA SOURCES: Data for this work were collected from the published literature, textbooks, and the Internet. CONCLUSIONS: It is important to be aware of the existence of this entity in abnormal locations. In many situations, malignancy can be mimicked, especially when the lesion is ulcerated and is accompanied by lymph node involvement. Misinterpreting large, rapidly growing nodules of malakoplakia as tumor might lead to overstaging. Pathologists should be also aware of the possibility of malakoplakia coexisting with other lesions, such as tuberculosis and carcinoma, in the same specimen. PMID- 17284118 TI - Primary central nervous system histiocytic sarcoma with relapse to mediastinum: a case report and review of the literature. AB - Histiocytic sarcoma is a rare, malignant neoplasm of the lymphohematopoietic system that usually occurs in the skin, lymph node, and intestinal tract. Here we describe a unique case of primary central nervous system histiocytic sarcoma that initially showed an indolent clinical course following local resection and radiotherapy. However, relapse of disease within the mediastinum was noted 3 1/2 years later. Biopsies of the initial brain lesion and subsequent mediastinal recurrence each revealed an identical, diffuse proliferation of histiocytes with expression of CD45, CD68, and CD163 but not pan-cytokeratin, epithelial membrane antigen, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, ALK-1, PAX 5, CAM 5.2, S100, CD1a, or glial fibrillary acidic protein. In the literature, central nervous system histiocytic sarcoma portends a poor prognosis with median survival of 4.5 months. To our knowledge, this case represents the first case of "low-grade" primary central nervous system histiocytic sarcoma with relatively indolent clinical course. A thorough discussion of the differential diagnosis of histiocytic sarcoma and a review of primary central nervous system histiocytic sarcoma are also presented. PMID- 17284119 TI - Intranodal palisaded myofibroblastoma. AB - Intranodal palisaded myofibroblastoma (IPM) usually presents as a painless, slow growing inguinal mass. Our review of 42 cases from 13 publications indicates that two thirds of IPMs occur between the ages of 45 and 55 years, the male-female ratio is 2:1, and there is a lack of ethnic predilection. Grossly, the IPM cut surface shows areas of hemorrhage. Five microscopic features are seen: (a) compressed remnants of lymphoid tissue at the periphery; (b) spindle cells with nuclear palisading; (c) intraparenchymal hemorrhage and erythrocyte extravasation; (d) so-called amianthoid fibers; and (e) intracellular and extracellular fuchsinophilic bodies that stain positive for smooth muscle actin. Immunohistochemically, IPM is positive for smooth muscle actin and cyclin D1 and negative for S100, glial fibrillary acidic protein, CD34, and desmin, and it shows a low proliferative index of Ki-67. Electron microscopy demonstrates features of myofibroblasts and smooth muscle cells. Excellent prognosis is seen after surgical treatment, with an approximately 6% recurrence rate and no malignant transformation. PMID- 17284120 TI - An in-depth look at Leydig cell tumor of the testis. AB - Leydig cell tumor (LCT) is a rare tumor of the male testicular interstitium. This article provides an overview of the major pathologic manifestations of LCT of the testis; patient characteristics; clinical, radiologic, and laboratory features; prognosis; and management. LCTs of the testis are frequently hormonally active, leading to either feminizing or virilizing syndromes. The tumor is usually benign, but malignant variants can occur. The pathologic diagnosis of LCT is usually made based on morphologic characteristics of the tumor cells. The significance of Reinke crystals in the diagnosis of LCT both cytologically and histologically is underscored. Pathologists have to be familiar with the diagnostic histopathologic features, immunohistochemical panel of this tumor, and its principal differential diagnoses to prevent tumor misdiagnosis. PMID- 17284122 TI - Treating depression complicated by comorbid medical illness or anxiety. AB - In this online activity, Trivedi discusses pharmacotherapy treatments for depression in the presence of comorbid medical illness or physical symptoms. The focus is on key aspects of treatment such as remission as the treatment goal, effects of different classes of antidepressants, and benefits of using treatment algorithms. Clayton addresses issues related to comorbid depression and anxiety including prevalence and recognition, risk factors and outcomes, and treatment considerations. Frank highlights the importance of psychotherapy in the treatment of complicated depression, citing empirically validated psychotherapies for acute depressive episodes as well as describing how to apply psychotherapy to medical patients with depression. PMID- 17284123 TI - The art and science of switching antipsychotic medications, part 2. AB - In the presentation "Switching and Metabolic Syndrome," Weiden summarizes reasons to switch antipsychotics, highlighting weight gain and other metabolic adverse events as recent treatment targets. In "Texas Medication Algorithm Project (TMAP)," Miller reviews the TMAP study design, discusses results related to the algorithm versus treatment as usual, and concludes with the implications of the study. Lambert's presentation, "Dosing and Titration Strategies to Optimize Patient Outcome When Switching Antipsychotic Therapy," reviews the decision making process when switching patients' medication, addresses dosing and titration strategies to effectively transition between medications, and examines other factors to consider when switching pharmacotherapy. PMID- 17284125 TI - Antipsychotics in the treatment of delirium: a systematic review. AB - OBJECTIVE: Antipsychotics are frequently used in the management of delirium, although there is limited information regarding the safety and efficacy of antipsychotics in treating delirium. The purpose of this study was to systematically evaluate the evidence for the efficacy and safety of antipsychotics in treating delirium. SOURCES: MEDLINE (July 1980 to July 2005) and Cochrane databases were searched for English language articles using keywords. STUDY SELECTION: Prospective studies with standardized criteria for diagnosing delirium and evaluating its severity. DATA SYNTHESIS: In total, 14 studies (9 single agent studies and 5 comparison trials) met inclusion criteria. Study medications included haloperidol, chlorpromazine, olanzapine, risperidone, and quetiapine. Improvements in delirium severity were reported with all of these antipsychotic medications. No study included a placebo comparison to account for spontaneous improvements in delirium. Other methodological limitations included inadequate blinding, randomization, and handling of participant withdrawals. The improvements in delirium tended to occur soon after initiation of treatment, and most of the studies examined used relatively low doses of antipsychotic medication. Serious adverse events attributable to antipsychotic medication were uncommon in studies, although side effects were not evaluated systematically in most studies. CONCLUSION: To date, there are no published double-blind, randomized, placebo-controlled trials to establish the efficacy or safety of any antipsychotic medication in the management of delirium. There is limited evidence from uncontrolled studies that supports the use of low-dose, short-term treatment of delirium with some antipsychotics. Further study with well-designed clinical trials is required in this area. PMID- 17284126 TI - Signs and symptoms associated with the metabolic syndrome in psychiatric inpatients receiving antipsychotics: a retrospective chart review. AB - OBJECTIVE: The metabolic syndrome has been recognized as a major health risk for patients taking atypical antipsychotics. Few studies, however, have examined large samples of psychiatric patients to explore the prevalence of the signs and symptoms associated with this condition. METHOD: The investigators retrospectively identified all inpatient admissions at the study site who were treated with antipsychotics during 2003 (N = 1691) and extracted demographic and clinical data (including measures associated with the syndrome: body mass index > 30 kg/m2, dyslipidemia, diagnosis of hypertension or diabetes). Stepwise logistic regression was used to identify variables associated with each correlate of the syndrome. RESULTS: In the majority of this sample (69.3%), at least 1 correlate of the metabolic syndrome was present. The odds that a patient would have 1 or more of these measures were approximately 8 times greater for those receiving clozapine than for those receiving another anti-psychotic medication. These patients also had increased odds (odds ratio = 2.5) of having hypertension or diabetes. In the subsample of patients with documentation for all 5 correlates of the metabolic syndrome (N = 362), 18.8% had > or = 3 of 5. CONCLUSION: The prevalence of at least 3 correlates in psychiatric inpatients receiving antipsychotics is probably an underestimate, because diagnosis was substituted for the blood pressure and glucose measures. Nonetheless, these findings support the call for routine screening for metabolic symptoms in patients receiving antipsychotics. The risk for these symptoms may be particularly high in some subgroups identified, such as patients older than 50 years and those taking clozapine or multiple antipsychotics. PMID- 17284127 TI - Efficacy and safety of aripiprazole in the acute treatment of schizophrenia in Chinese patients with risperidone as an active control: a randomized trial. AB - OBJECTIVE: Asian populations may differ from other races in response to antipsychotics. Studies of aripiprazole in Asian populations are scarce. This study aimed to investigate the efficacy, safety, and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder. METHOD: This 4-week, double-blind, randomized, parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005. A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomly assigned (with a randomization ratio of 3:2) to 15 mg/day of aripiprazole (N = 49) or 6 mg/day of risperidone (N = 34). Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores and Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement scale scores. Extrapyramidal symptoms (EPS), weight gain, serum prolactin level, QTc interval, and self-reported adverse events were assessed as measures of safety and tolerability. RESULTS: Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total, PANSS positive, PANSS negative, and CGI-S scores at study endpoint (all p < .001). Significant improvement was noted in the first week of treatment for both treatment groups. There were no significant differences in efficacy measures between treatment groups. Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale (p < .005) and less serum prolactin level elevation (p < .001) than risperidone. Both groups showed mild weight gain. No patients showed clinically significant QTc interval prolongation in this study. CONCLUSION: Compared with risperidone 6 mg/day, aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short term treatment of Chinese patients with acute schizophrenia. In this group of Chinese patients, the overall response to aripiprazole did not differ from that of white patients. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00283179. PMID- 17284128 TI - A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance. AB - OBJECTIVE: The relative short-term efficacy and long-term benefits of pharmacologic versus psychotherapeutic interventions have not been studied for posttraumatic stress disorder (PTSD). This study compared the efficacy of a selective serotonin reup-take inhibitor (SSRI), fluoxetine, with a psychotherapeutic treatment, eye movement desensitization and reprocessing (EMDR), and pill placebo and measured maintenance of treatment gains at 6-month follow-up. METHOD: Eighty-eight PTSD subjects diagnosed according to DSM-IV criteria were randomly assigned to EMDR, fluoxetine, or pill placebo. They received 8 weeks of treatment and were assessed by blind raters posttreatment and at 6-month follow-up. The primary outcome measure was the Clinician-Administered PTSD Scale, DSM-IV version, and the secondary outcome measure was the Beck Depression Inventory-II. The study ran from July 2000 through July 2003. RESULTS: The psychotherapy intervention was more successful than pharmacotherapy in achieving sustained reductions in PTSD and depression symptoms, but this benefit accrued primarily for adult-onset trauma survivors. At 6-month follow-up, 75.0% of adult-onset versus 33.3% of child-onset trauma subjects receiving EMDR achieved asymptomatic end-state functioning compared with none in the fluoxetine group. For most childhood-onset trauma patients, neither treatment produced complete symptom remission. CONCLUSIONS: This study supports the efficacy of brief EMDR treatment to produce substantial and sustained reduction of PTSD and depression in most victims of adult-onset trauma. It suggests a role for SSRIs as a reliable first-line intervention to achieve moderate symptom relief for adult victims of childhood-onset trauma. Future research should assess the impact of lengthier intervention, combination treatments, and treatment sequencing on the resolution of PTSD in adults with childhood-onset trauma. PMID- 17284129 TI - Indicators of mania in depressed outpatients: a retrospective analysis of data from the Kansas 1500 study. AB - OBJECTIVE: Previous prospective studies have shown that unipolar depressed patients often switch to a manic episode. Some of these studies have reported that the conversion to bipolar disorder is predicted by an early onset of depression, a positive family history for mania, and psychotic symptoms. The present study examines the strength of the relationship between these 3 indicators, both alone and in combination, and the presence of mania in a large retrospective analysis. METHOD: 1458 consecutive admissions to a large, Midwestern university outpatient clinic between 1981 and 1986 were interviewed, and 1002 patients met DSM-III inclusive criteria for major depressive disorder. Of these, information about age at onset of depression, family history of mania, and psychotic symptoms was available on 744 outpatients. Two structured interviews were used to assess the 3 indicators. RESULTS: In this large depressed outpatient sample, the incidence of lifetime mania was 27%. Each of the 3 indicators was significantly associated with the report of mania (p < .0001 for all 3 indicators). The rates of mania increased as the number of indicators increased. Psychotic symptoms were the strongest indicator, followed by a family history of mania and an early age at onset of depression. CONCLUSION: Depressed patients with 1 or more of these 3 indicators should be monitored for the presence of bipolar disorder. Patients with 2 or more of these indicators are especially at risk to develop mania. PMID- 17284132 TI - Personality disorder and cardiovascular disease: results from a national household survey. AB - OBJECTIVE: Little is known about the physical health of personality-disordered people. This study investigated associations between personality disorder and cardiovascular disease in a large, nationally representative sample from Great Britain. METHOD: A random sample of 8580 adults aged 16 to 74 years, living in England, Wales, and Scotland in 2000 was screened for the presence of personality disorders using the screening questionnaire of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders. Self-reported stroke or ischemic heart disease was ascertained. Age, sex, social class (by occupation), self-reported hypertension or diabetes, smoking history, and alcoholism were entered into regression models as potential confounding/mediating factors. RESULTS: Participants screening positive for any personality disorder were more likely to report experiencing a stroke and ischemic heart disease (age- and sex-adjusted odds ratios [ORs] were 2.1 [95% CI, 1.2 to 3.8] and 1.5 [95% CI, 1.1 to 2.1], respectively). After adjusting for potential confounders, significant associations were found between any personality disorder and stroke (OR = 1.9; 95% CI, 1.0 to 3.5) and any personality disorder and ischemic heart disease (OR = 1.4; 95% CI, 1.0 to 1.9). After adjustment, avoidant (OR = 4.0; 95% CI, 1.2 to 13.3), obsessive-compulsive (OR = 2.9; 95% CI, 1.3 to 6.6), and borderline personality disorders (OR = 8.5; 95% CI, 1.0 to 72.8) were significantly associated with stroke. Ischemic heart disease was significantly associated with avoidant (OR = 2.2; 95% CI, 1.1 to 4.5), paranoid (OR = 2.1; 95% CI, 1.0 to 4.3), schizotypal (OR = 3.6; 95% CI, 1.5 to 8.6), schizoid (OR = 1.6; 95% CI, 1.1 to 2.4), and borderline personality disorders (OR = 7.2; 95% CI, 2.1 to 24.3). CONCLUSION: People at risk for personality disorder are also at increased risk for cardiovascular disease. This increased risk is not explained by differences in socioeconomic status or lifestyle. Dysfunctional personality traits may have a direct role in the etiology of cardiovascular disease. PMID- 17284130 TI - Early symptomatic worsening during treatment with fluoxetine in major depressive disorder: prevalence and implications. AB - BACKGROUND: A subset of patients experience worsening of depressed mood after beginning antidepressant treatment, which could represent the natural history of the illness or a treatment-related effect. While patterns of response have been examined as possible predictors of outcome, the clinical correlates and implications of early worsening per se have not been investigated. METHOD: In a post hoc analysis, we studied the clinical correlates of early worsening in a large sample of outpatients (N = 694) diagnosed with a DSM-III-R-defined major depressive episode and treated with fluoxetine (20 mg/day) for up to 12 weeks. We defined early worsening as an increase of at least 5 points on a modified 17-item Hamilton Rating Scale for Depression (mHAM-D, including reverse vegetative symptoms) compared to the previous visit, and occurring during the acute phase of treatment. The primary analysis compared remission and response at week 12 between those patients with and without worsening. RESULTS: In our sample, 211 patients (30.4%) experienced early worsening of depression. An increase in mHAM-D score at week 2, 3, 4, or 6 was associated with a significantly lower probability of remission and response at both week 8 and week 12, while no significant difference was observed in study discontinuation. Baseline features, including gender, age, mHAM-D score at entry, number of previous depressive episodes, and duration of illness were not associated with the development of early worsening during fluoxetine treatment. CONCLUSION: Early clinical worsening is common and associated with a decreased likelihood of achieving remission. PMID- 17284131 TI - Relapse prevention of panic disorder in adult outpatient responders to treatment with venlafaxine extended release. AB - OBJECTIVE: To compare the long-term efficacy of venlafaxine extended release (ER) with placebo in preventing panic disorder relapse in out-patient treatment responders. METHOD: Outpatients aged > or = 18 years who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for panic disorder with or without agoraphobia for at least the previous 3 months, with > or = 6 full symptom panic attacks in the 2 weeks prior to screening and > or = 3 in the 2 weeks before baseline and a Clinical Global Impressions-Severity of Illness rating > or = 4 at screen were eligible to participate. Outpatients received flexible-dose (75-225 mg/day) venla-faxine ER for 12 weeks. Treatment responders were randomly assigned to venlafaxine ER or placebo for 26 weeks. Criteria for response were < or = 1 panic attack per week during the last 2 weeks of open-label treatment and a Clinical Global Impressions-Improvement score of 1 or 2. The primary endpoint, time to relapse during double-blind treatment, defined as > or = 2 full symptom panic attacks per week for 2 consecutive weeks or discontinuation due to loss of effectiveness, was evaluated using Kaplan-Meier survival analysis. The study was conducted between December 2001 and August 2003. RESULTS: The intent-to-treat population had 291 patients in the open-label phase and 169 in the double-blind phase (placebo, N = 80; venlafaxine ER, N = 89; mean daily dose 165-171 mg). Time to relapse was significantly longer with venlafaxine ER than placebo (p < .001). All secondary measures of panic attack treatment efficacy, quality of life, and disability were significantly better with venlafaxine ER than placebo (p < or = .005). CONCLUSION: Venlafaxine ER was safe, well tolerated, and effective in preventing relapse in outpatients with panic disorder. PMID- 17284133 TI - Association of subjective well-being, symptoms, and side effects with compliance after 12 months of treatment in schizophrenia. AB - OBJECTIVE: Subjective well-being is considered important for compliance with antipsychotic treatment. The objective of this post hoc analysis of data from German patients in the Schizophrenia Outpatient Health Outcomes study was to investigate subjective well-being and compliance, with consideration of clinical symptoms and side effects, in outpatients diagnosed with schizophrenia. METHOD: In a multicenter observational study of 2960 patients with DSM-IV-defined schizophrenia recruited between January and December 2001, subjective well-being was measured during 12 months with the Subjective Well-Being Under Neuroleptic Treatment Scale, short version (SWN-K). Compliance was self- and physician-rated. The association of compliance with clinical parameters was assessed by logistic regression. RESULTS: Factor analysis resulted in 3 factors: SWN-K (r2 = 0.867), clinical symptoms (r2 = 0.744), and side effects (r2 = 0.420). The odds for being compliant were 1.363 times higher if the SWN-K score increased by 20 points. Changes in positive symptoms (OR = 0.773) and changes in extrapyramidal symptoms (OR = 0.830) were found to be associated with compliance. CONCLUSION: Compliance with antipsychotic medication was strongly associated with subjective well-being; further factors were clinical symptoms and side effects. PMID- 17284134 TI - Insight as a predictor of the outcome of first-episode nonaffective psychosis in a prospective cohort study in England. AB - OBJECTIVE: To estimate the effect of insight on time to relapse and readmission and on social function and symptoms after following up a cohort of first-episodes of nonaffective psychosis for 18 months. METHOD: Patients with first episodes of DSM-IV schizophreniform disorder, schizophrenia, schizoaffective disorder, delusional disorder, and psychosis not otherwise specified (excluding primary substance-induced or organic psychoses), aged 16 to 65 years, were recruited over the 26 months from July 1996 to September 1998 from consecutive admissions to day patient and inpatient units in England with a catchment area population of 2.3 million. They were interviewed with the Positive and Negative Syndrome Scale, Birchwood Insight Scale, and Social Functioning Scale at baseline and 18 months. RESULTS: The hazard ratio for relapse, per unit increase in the insight score, was estimated in a Cox proportional hazards model to be 0.943 (95% CI = 0.892 to 0.996; p = .035). Those with the best insight scores had an estimated rate of relapse that was 39% of that of those with the worst scores (95% CI = 16% to 93%). Readmission was highly correlated with relapse, so poor insight also predicted readmission (hazard ratio 0.934; 95% CI = 0.876 to 0.996; p = .036). However, insight did not independently predict symptoms or social function after adjustment for other predictors of outcome. CONCLUSION: Insight predicted both relapse and readmission. The details of the beliefs and assumptions determining outcome remain unclear, but intervening to alter them appears to be justified. PMID- 17284135 TI - Smoking as a risk factor for mental health disturbances after a disaster: a prospective comparative study. AB - OBJECTIVE: To assess whether smoking is a(n) (independent) risk factor for mental health problems among adult disaster victims and among a nonexposed comparison group. METHOD: Surveys were conducted 18 months (T1) and 4 years (T2) after a fireworks disaster in Enschede, the Netherlands (May 13, 2000), among adult victims (N = 662) and a comparison group (N = 526) of residents of a city located in another part of the Netherlands. The surveys included measures of smoking (Dutch Local and National Public Health Monitor); severe anxiety, depression, and hostility symptoms (the Symptom Checklist-90, revised); and disaster-related post traumatic stress disorder (PTSD; DSM-IV criteria) (the PTSD self-rating scale). RESULTS: Victims who smoked at T1 had a higher chance to suffer from severe anxiety symptoms (adjusted OR = 2.32 [95% CI = 1.19 to 4.53]), severe hostility symptoms (adjusted OR = 1.84 [95% CI = 1.06 to 3.22]), and disaster-related PTSD (adjusted OR = 2.64 [95% CI = 1.05 to 6.62]) at T2 than victims who did not smoke at T1, when controlling for symptoms at T1, demographic characteristics, and life events. Among the total comparison group, smoking was not an independent risk factor. However, smoking at T1 was associated with severe anxiety symptoms at T2 among controls who were confronted with stressful life events (adjusted OR = 4.11 [95% CI = 1.03 to 16.47]). CONCLUSIONS: Smoking is an independent risk factor for severe anxiety and hostility symptoms and PTSD among adult disaster victims and for anxiety symptoms among adult people who are confronted with stressful life events. Questions about smoking behavior among disaster victims may help to identify adult victims who are at risk for postevent mental health disturbances. PMID- 17284136 TI - A double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder. AB - BACKGROUND: The realization that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood has led to increased frequency of diagnosis and treatment in adults. Osmotic release oral system (OROS) methylpheni-date is a long-acting stimulant demonstrated to be effective in the treatment of children and adolescents with ADHD. METHOD: Forty-seven adults entered and 41 completed this double-blind, placebo-controlled, crossover trial of OROS methylphenidate. Each double-blind arm lasted 4 weeks; data were collected from August 2004 through December 2005. Subjects met both DSM-IV-TR and Utah Criteria for ADHD in adults. Outcome measures included the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), the adult ADHD-Rating Scale (ADHD-RS), and the Clinical Global Impressions-Improvement scale (CGI-I). At baseline, subjects were categorized as having significant emotional symptoms with the WRAADDS and/or significant oppositional-defiant symptoms using a self-report scale assessing the DSM-IV criteria for oppositional defiant disorder. RESULTS: 17% of the sample (N = 8) had ADHD alone, 38% (N = 18) had ADHD plus significant emotional symptoms, and 40% (N = 19) had ADHD with both significant emotional and oppositional symptoms. At a mean +/- SD dose of 64.0 +/- 23.3 (0.75 mg/kg), OROS methylphenidate proved superior to placebo for all clinical measures: total WRAADDS score decrease of 42% versus 13%, respectively, p < .001 and total ADHD RS score decrease of 41% versus 14%, respectively, p = .003, plus the subscales addressing inattention, hyperactivity/ impulsivity, and emotional dysregulation. CONCLUSIONS: OROS methylphenidate proved effective in treating adult ADHD. ADHD alone was relatively uncommon. Over 80% of our patients had ADHD with a combination of emotional and/or oppositional symptoms. PMID- 17284137 TI - Adequacy of treatment received by diagnosed and undiagnosed patients with bipolar I and II disorders. AB - OBJECTIVE: To investigate the adequacy of pharmacotherapy received by psychiatric inpatients and outpatients with a research diagnosis of bipolar I or II disorder, including patients both with and without a clinical diagnosis of bipolar disorder. METHOD: In the Jorvi Bipolar Study (JoBS), 1630 psychiatric inpatients and outpatients in 3 Finnish cities were systematically screened between January 1, 2002, and February 28, 2003, for bipolar I and II disorders using the Mood Disorder Questionnaire. By using SCID-I and -II interviews, 191 patients were diagnosed with bipolar disorder (90 bipolar I and 101 bipolar II). Information was collected on clinical history, diagnosis, and treatment. The adequacy of treatment received was evaluated. RESULTS: Of the 162 patients with previous bipolar disorder episodes, only 34 (20.9%) of all and 30 (55.5%) of those with a clinical diagnosis of bipolar disorder were using a mood stabilizer at onset of the index episode. Only 81 (42.4%) of all 191 patients and 76 (65.0%) of those diagnosed with bipolar disorder received adequate treatment for the acute index phase. The factor most strongly independently associated with adequate treatment was clinical diagnosis of bipolar disorder (OR = 25.34). In addition, rapid cycling (OR = 2.45), polyphasic index episode (OR = 2.41), or depressive index phase (OR = 3.36) independently predicted inadequate treatment. Outpatients received adequate treatment markedly less often than inpatients. CONCLUSIONS: Clinical diagnosis of bipolar disorder is by far the most important prerequisite for adequate treatment. Problems in treatment are associated mostly with outpatient settings, where adequacy of treatment of bipolar depression is a major concern. Lack of attention to the longitudinal course of illness is another major problem area. PMID- 17284138 TI - Efficacy and safety of intramuscular aripiprazole in patients with acute agitation: a randomized, double-blind, placebo-controlled trial. AB - OBJECTIVE: This multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of intramuscular (IM) aripiprazole in patients with acute agitation with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or schizo-phreniform disorder. METHOD: Patients were randomly assigned to IM aripiprazole 1 mg, 5.25 mg, 9.75 mg, or 15 mg; IM haloperidol 7.5 mg; or placebo and observed for 24 hours. The primary efficacy measure was mean change in the Positive and Negative Syndrome Scale-Excited Component (PEC) score from baseline to 2 hours after initial dosing. Secondary measures included the Agitation-Calmness Evaluation Scale (ACES) score. The study was carried out at 50 centers worldwide between April 2002 and January 2003. RESULTS: A total of 357 patients were randomly assigned to treatment. Intramuscular aripiprazole 5.25 mg, 9.75 mg, and 15 mg and IM haloperidol 7.5 mg demonstrated significantly greater reduction in the primary efficacy measure versus placebo. These changes were statistically significant as early as 45 minutes for the IM aripiprazole 9.75-mg group, with a trend toward significance (p = .051) at 30 minutes. Intramuscular haloperidol 7.5 mg first showed a significant reduction in PEC score versus placebo at 105 minutes. At 30 minutes, significantly more patients responded (defined as a greater than or equal to 40% reduction in PEC score) to IM aripiprazole 9.75 mg versus placebo (27% vs. 13%, p = .05). Intramuscular aripiprazole 9.75 mg significantly improved agitation, without oversedation, as measured by change in ACES score from baseline to 2 hours versus placebo (p = .003). No patient discontinued the study because of treatment-emergent adverse events. Extrapyramidal symptoms occurred most frequently in the IM haloperidol group. The most common adverse event in IM aripiprazole recipients was headache. CONCLUSION: Intramuscular aripiprazole 9.75 mg is a rapidly effective and well tolerated alternative to IM haloperidol for the control of agitation, without oversedation, in patients with schizophrenia, schizo-affective disorder, or schizophreniform disorder. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00036127. PMID- 17284139 TI - Refining the questions in women's mental health. PMID- 17284141 TI - Postpartum-onset obsessive-compulsive disorder: incidence, clinical features, and related factors. AB - OBJECTIVE: The aims of this study were to investigate the incidence rate and symptomatology of postpartum-onset obsessive-compulsive disorder (PPOCD), to investigate the factors associated with PPOCD, and to compare clinical characteristics of obsessive-compulsive disorder (OCD) with and without postpartum onset. METHOD: The study data were collected from 302 women who delivered at a child and maternity hospital in Turkey from August 2005 to November 2005 and a control group of 33 women who were admitted to the psychiatric outpatient clinic of a university hospital during the same time period and who met DSM-IV criteria for OCD. The 2 clinical interviews with women who delivered were performed face-to-face on the first day after childbirth and at 6 weeks postnatally. OCD and comorbid Axis II disorders were diagnosed by means of the Structured Clinical Interview for DSM-IV and the Structured Clinical Interview for DSM-III-R Personality Disorders, respectively. Obsessive-compulsive symptomatology was assessed with the Yale-Brown Obsessive Compulsive Scale. RESULTS: The incidence of PPOCD was 4% at 6 weeks postnatally. The most common obsessions in women with PPOCD were contamination (75%), aggressive (33.3%), and symmetry/exactness (33.3%), and the most common compulsions were cleaning/ washing (66.7%) and checking (58.3%). The patients with PPOCD had significantly more frequent aggressive obsessions (p = .039) and less severe obsessive compulsive symptoms (p = .013) than the OCD patients without postpartum onset. The predictors of PPOCD were avoidant (p = .000) and obsessive-compulsive (p = .004) personality disorders. CONCLUSIONS: This study suggests that the puerperium is a risk period in terms of new-onset OCD and that avoidant and obsessive compulsive personality disorders predict PPOCD. PMID- 17284140 TI - Self-injurious behavior in a community sample of young women: relationship with childhood abuse and other types of self-damaging behaviors. AB - OBJECTIVE: The prevalence of self-injurious behavior (SIB) in the general population is unknown. The present study aims to assess the prevalence and dimensionality of a large spectrum of SIBs in a community sample of young women. METHOD: A cohort of female subjects aged 18 through 25 years resident in 2 areas of a large city was involved in the study, which was conducted from December 1996 to August 1998. Subjects (N = 934) underwent a clinical interview to assess the presence of SIBs, childhood sexual and physical abuse, suicidality, use of illicit drugs, alcohol abuse, and DSM-IV lifetime eating disorder diagnosis. RESULTS: About 24% of the sample reported some type of SIB. The factor analysis revealed that the different types of SIBs tend to group into 4 dimensions: 2 characterized by impulsive features and the other 2 by compulsive features. Body image disturbance (p < .01), emotional distress (p < .001), alcohol/substance misuse (p < .05), and suicide attempts (p < .01) were significantly associated with both compulsive and impulsive SIBs. In addition, the presence of impulsive SIBs was significantly predicted by a lower level of education (p < .05), lifetime eating disorders (p < .01), and childhood abuse (p < .05), whereas skin picking/self-biting was predicted by childhood sexual molestation (p < .04) and childhood rape (p < .005). CONCLUSION: Self-injurious behaviors are common among young women. There is a significant association between SIBs and other forms of direct and indirect self-damaging behaviors, including alcohol abuse, use of illicit substances, suicidality, and eating disorders. Further research is needed to better understand the nosology of this spectrum of behaviors. PMID- 17284142 TI - The evolving paradigm for bipolar disorder. PMID- 17284143 TI - Practical applications of recent antipsychotic effectiveness data. PMID- 17284144 TI - The psychopharmacology of violence with emphasis on schizophrenia, part 1: acute treatment. PMID- 17284145 TI - Sweat. PMID- 17284147 TI - Predicting pharmacotherapy outcome from a retrospective chart study? PMID- 17284148 TI - Quality of life among patients with depression. PMID- 17284150 TI - Galantamine and QTc prolongation. PMID- 17284151 TI - Beneficial effects of the antiglutamatergic agent riluzole in a patient diagnosed with trichotillomania. PMID- 17284155 TI - Use of modern contraception by the poor is falling behind. AB - BACKGROUND: The widespread increase in the use of contraception, due to multiple factors including improved access to modern contraception, is one of the most dramatic social transformations of the past fifty years. This study explores whether the global progress in the use of modern contraceptives has also benefited the poorest. METHODS AND FINDINGS: Demographic and Health Surveys from 55 developing countries were analyzed using wealth indices that allow the identification of the absolute poor within each country. This article explores the macro level determinants of the differences in the use of modern contraceptives between the poor and the national averages of several countries. Despite increases in national averages, use of modern contraception by the absolute poor remains low. South and Southeast Asia have relatively high rates of modern contraception in the absolute poor, on average 17% higher than in Latin America. Over time the gaps in use persist and are increasing. Latin America exhibits significantly larger gaps in use between the poor and the averages, while gaps in sub-Saharan Africa are on average smaller by 15.8% and in Southeast Asia by 11.6%. CONCLUSIONS: The secular trend of increasing rates of modern contraceptive use has not resulted in a decrease of the gap in use for those living in absolute poverty. Countries with large economic inequalities also exhibit large inequalities in modern contraceptive use. In addition to macro level factors that influence contraceptive use, such as economic development and provision of reproductive health services, there are strong regional variations, with sub-Saharan Africa exhibiting the lowest national rates of use, South and Southeast Asia the highest use among the poor, and Latin America the largest inequalities in use. PMID- 17284154 TI - Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. AB - BACKGROUND: Cryptococcosis is a life-threatening opportunistic fungal infection in both HIV-positive and -negative patients. Information on clinical presentation and therapeutic guidelines, derived mostly from clinical trials performed before introduction of highly active antiretroviral therapy in patients with cryptococcal meningoencephalitis, is missing data on extrameningeal involvement and infections by serotype D as opposed to serotype A of Cryptococcus neoformans. METHODS AND FINDINGS: The prospective multicenter study CryptoA/D was designed in France (1997-2001) to analyse the factors influencing clinical presentation and outcome without the bias of inclusion into therapeutic trials. Of the 230 patients enrolled, 177 (77%) were HIV-positive, 50 (22%) were female, and 161 (72.5%) were infected with serotype A. Based on culture results at baseline, cryptococcosis was more severe in men, in HIV-positive patients, and in patients infected with serotype A. Factors independently associated with mycological failure at week 2 independent of HIV status were initial dissemination (OR, 2.4 [95% confidence interval (CI), 1.2-4.9]), high (>1:512) serum antigen titre (OR, 2.6 [1.3-5.4]), and lack of flucytosine during induction therapy (OR, 3.8 [1.9 7.8]). The three-month survival was shorter in patients with abnormal neurology or brain imaging at baseline, and in those with haematological malignancy. CONCLUSIONS: Thus sex, HIV status, and infecting serotype are major determinants of presentation and outcome during cryptococcosis. We propose a modification of current guidelines for the initial management of cryptococcosis based on systematic fungal burden evaluation. PMID- 17284156 TI - Management of cryptococcosis: how are we doing? PMID- 17284157 TI - Contraceptive use and the poor: a matter of choice? PMID- 17284158 TI - The role of general practitioners in the follow up of type 1 diabetic patients with insulin pump therapy. PMID- 17284163 TI - Small-angle X-ray scattering from RNA, proteins, and protein complexes. AB - Small-angle X-ray scattering (SAXS) is increasingly used to characterize the structure and interactions of biological macromolecules and their complexes in solution. Although still a low-resolution technique, the advent of high-flux synchrotron sources and the development of algorithms for the reconstruction of 3 D electron density maps from 1-D scattering profiles have made possible the generation of useful low-resolution molecular models from SAXS data. Furthermore, SAXS is well suited for the study of unfolded or partially folded conformational ensembles as a function of time or solution conditions. Here, we review recently developed algorithms for 3-D structure modeling and applications to protein complexes. Furthermore, we discuss the emerging use of SAXS as a tool to study membrane protein-detergent complexes. SAXS is proving useful to study the folding of functional RNA molecules, and finally we discuss uses of SAXS to study ensembles of denatured proteins. PMID- 17284165 TI - Control over action potential, calcium peak and average fluxes in the cyclic quasi-steady-state ion transport system in cardiac myocytes: in silico studies. AB - MCA (metabolic control analysis) was originally developed to deal with steady state systems. In the present theoretical study, the control analysis is applied to the cyclic quasi-steady-state system of ion transport in cardiac myocytes. It is demonstrated that the metabolic control of particular components (channels, exchangers, pumps) of the system over such quasi-steady-state variables as action potential amplitude, action potential duration, area under the Ca2+ peak and average fluxes through particular channels during one oscillation period can be defined and calculated. It is shown that the control over particular variables in the analysed, periodical system is distributed among many (potentially all) components of the system. Nevertheless, some components seem to exert much more control than other components, and different variables are controlled to the greatest extent by different channels. Finally, it is hypothesized that the Na+ and K+ transport system exerts a significant control over the Ca2+ transport system, but not vice versa. PMID- 17284166 TI - Evaluation of ischaemia-modified albumin as a marker of myocardial ischaemia in end-stage renal disease. AB - The early diagnosis of myocardial ischaemia is problematic in patients with ESRD (end-stage renal disease). The aim of the present study was to determine whether IMA (ischaemia-modified albumin) increases during dobutamine stress and detects myocardial ischaemia in patients with ESRD. A total of 114 renal transplant candidates were studied prospectively, and all received DSE (dobutamine stress echocardiography). IMA levels were taken at baseline and 1 h after cessation of DSE. A total of 35 patients (31%) had a positive DSE result. Baseline IMA levels were not significantly different in the DSE-positive and -negative groups. The increase in IMA was significantly higher in the DSE-positive group compared with those with no ischaemic response (26.5 +/- 19.1 compared with 8.2 +/- 9.6 kU/l respectively; P = 0.007; where kU is kilo-units). From ROC (receiver operator charactertistic) curve analysis, the optimal IMA increase to predict an ischaemic response was 20 kU/l, with a sensitivity of 81% and a specificity of 72% [area under the curve, 0.80 (95% confidence interval, 0.44-0.94); P = 0.03]. There were 18 deaths, ten of which were cardiac in nature over a follow up period of 2.25 +/ 0.71 years. An increase in IMA > or = 20 kU/l was associated with significantly worse survival (P = 0.02). In conclusion, IMA is a moderately accurate marker of myocardial ischaemia in ESRD. Patients with an increase in IMA > or = 20 kU/l during DSE had significantly worse survival. PMID- 17284167 TI - Characterization of the transactivation domain in the peroxisome-proliferator activated receptor gamma co-activator (PGC-1). AB - The PGC-1s (peroxisome-proliferator-activated receptor gamma co-activators) are a family of transcriptional regulators that induce the expression of various metabolic genes. PGC-1 proteins stimulate genes involved in mitochondrial biogenesis, fatty acid oxidation and hepatic gluconeogenesis. Previous studies have demonstrated that the PGC-1alpha and beta isoforms interact with nuclear receptors through the conserved LXXLL (leucine-X-X-leucine-leucine) motifs. In the present study, we have investigated the mechanisms by which these PGC-1 isoforms stimulate gene expression. We have determined that the N-terminus of PGC 1 is responsible for transcriptional activation. Two conserved peptide motifs were identified in the N-terminus of PGC-1alpha and beta isoforms. These domains were named AD1 and AD2 (activation domain 1 and 2). Deletion of both of these motifs decreased the induction of various PGC-1-regulated genes including the PEPCK (phosphoenolpyruvate carboxykinase) and CPT-I (carnitine palmitoyltransferase-I) genes. It was determined that amino acids containing a negative charge in AD1 and the leucine residues in AD2 were important for the transcriptional induction of the PEPCK and CPT-I genes. Disruption of the AD motifs did not diminish the ability of the PGC-1alpha protein to associate with the PEPCK or CPT-I genes. In addition, deletion of the AD domains did not eliminate the ability of PGC-1alpha to interact with the thyroid hormone receptor. The data indicate that the AD1 and AD2 motifs mediate the induction of many PGC-1- responsive genes, but they do not contribute to the recruitment of PGC-1 to target genes. PMID- 17284168 TI - Serotonergic genes modulate amygdala activity in major depression. AB - Serotonergic genes have been implicated in the pathogenesis of depression probably via their influence on neural activity during emotion processing. This study used an imaging genomics approach to investigate amygdala activity in major depression as a function of common functional polymorphisms in the serotonin transporter gene (5-HTTLPR) and the serotonin receptor 1A gene (5-HT(1A) 1019C/G). In 27 medicated patients with major depression, amygdala responses to happy, sad and angry faces were assessed using functional magnetic resonance imaging at 3 Tesla. Patients were genotyped for the 5-HT(1A)-1019C/G and the 5 HTTLPR polymorphism, including the newly described 5-HTT-rs25531 single nucleotide polymorphism. Risk allele carriers for either gene showed significantly increased bilateral amygdala activation in response to emotional stimuli, implicating an additive effect of both genotypes. Our data suggest that the genetic susceptibility for major depression might be transported via dysfunctional neural activity in brain regions critical for emotion processing. PMID- 17284169 TI - RhoA, encoding a Rho GTPase, is associated with smoking initiation. AB - We used microarray analysis of acute nicotine responses in mouse brain to choose rationale candidates for human association studies on tobacco smoking and nicotine dependence (ND). Microarray studies on the time-course of acute response to nicotine in mouse brain identified 95 genes regulated in ventral tegmental area. Among these, 30 genes were part of a gene network, with functions relevant to neural plasticity. On this basis and their known roles in drug abuse or synaptic plasticity, we chose the genes RhoA and Ywhag as candidates for human association studies. A synteny search identified human orthologs and we investigated their role in tobacco smoking and ND in a human case-control association study. We genotyped five and three single nucleotide polymorphisms from the RhoA and Ywhag genes, respectively. Both single marker and haplotype analyses were negative for the Ywhag gene. For the RhoA gene, rs2878298 showed highly significant genotypic association with both smoking initiation (SI) and ND (P = 0.00005 for SI and P = 0.0007 for ND). In the allelic analyses, rs2878298 was only significant for SI. In the multimarker haplotype analyses, significant association with SI was found for the RhoA gene (empirical global P values ranged from 9 x 10(-5) to 10(-5)). In all multimarker combinations analyzed, with or without inclusion of the single most significant marker rs2878298, identical risk and protective haplotypes were identified. Our results indicated that the RhoA gene is likely involved in initiation of tobacco smoking and ND. Replication and future model system studies will be needed to validate the role of RhoA gene in SI and ND. PMID- 17284170 TI - Disruption of the vasopressin 1b receptor gene impairs the attack component of aggressive behavior in mice. AB - Vasopressin affects behavior via its two brain receptors, the vasopressin 1a and vasopressin 1b receptors (Avpr1b). Recent work from our laboratory has shown that disruption of the Avpr1b gene reduces intermale aggression and reduces social motivation. Here, we further characterized the aggressive phenotype in Avpr1b -/- (knockout) mice. We tested maternal aggression and predatory behavior. We also analyzed the extent to which food deprivation and competition over food increases intermale aggression. We quantified defensive behavior in Avpr1b -/- mice and later tested offensive aggression in these same mice. Our results show that attack behavior toward a conspecific is consistently reduced in Avpr1b -/- mice. Predatory behavior is normal, suggesting that the deficit is not because of a global inability to detect and attack stimuli. Food deprivation, competition for food and previous experience increase aggression in both Avpr1b +/+ and -/- mice. However, in these circumstances, the level of aggression seen in knockout mice is still less than that observed in wild-type mice. Defensive avoidance behaviors, such as boxing and fleeing, are largely intact in knockout mice. Avpr1b -/- mice do not display as many 'retaliatory' attacks as the Avpr1b +/+ mice. Interestingly, when territorial aggression was measured following the defensive behavior testing, Avpr1b -/- mice typically show less initial aggressive behavior than wild-type mice, but do show a significant increase in aggression with repeated testing. These studies confirm that deficits in aggression in Avpr1b -/- mice are limited to aggressive behavior involving the attack of a conspecific. We hypothesize that Avpr1b plays an important role in the central processing that couples the detection and perception of social cues (which appears normal) with the appropriate behavioral response. PMID- 17284171 TI - Viruses and dendritic cells: enemy mine. AB - Dendritic cells (DCs) act not only as sentinels for detection of, but also as target cells for viruses, and this can be important for viral transport and spread. All subsets of DCs are equipped with a battery of receptors recognizing virus-associated molecular signatures, and recognition of those launches a maturation programme that results in substantial alterations of morphology, motility and the DCs' interactive properties with the extracellular matrix and scanning T cells. In addition to being sensed, viruses are internalized into DCs and, for the major proportion, processed into peptides that are subsequently presented by major histocompatibility complex (MHC) molecules. Transmission of virus to T cells can occur after completion of their replication cycle if the intracellular milieu of the DC permits that. Alternatively, viruses can remain protected from degradation following entrapment by pattern recognition receptors in intracellular compartments, also referred to as virosomes, which translocate towards the DC/T cell interface. Most likely, transfer of virus to T cells occurs in these junctions, referred to as infectious synapses. In addition to promoting DC maturation, many viruses are able to downmodulate DC development and functions in order to evade immune recognition or to induce a generalized immunosuppression. PMID- 17284172 TI - Signalling and phagocytosis in the orchestration of host defence. AB - Dendritic cells (DCs) orchestrate either tolerance or immunity. At the heart of this function lies phagocytosis, which allows DCs to sample the tissue microenvironment and deliver both its self and non-self constituents into endocytic compartments for clearance, degradation and presentation by major histocompatibility complex (MHC) molecules. Depending on the type of signalling pathways triggered during phagocytosis, DCs deliver appropriate signals to T cells that determine either their tolerance or activation and differentiation. Here I draw attention to the ability of DCs to read the contents of their phagosomes depending on the type of compartmentalized signalling pathways engaged during internalization. Toll-like receptors (TLRs) engaged during phagocytosis of microbial pathogens, but not syngeneic apoptotic cells exert phagosome autonomous control on both the kinetics and outcome of phagosome maturation. By bearing the assembly of signalling complexes on their membranes, individual phagosomes undergo separate programmes of maturation irrespective of the activation status of the DC carrying them. Phagosomes carrying microbial cargo are favoured for MHC class II presentation precluding phagosomes carrying self from contributing to the first signal delivered to T cells - the peptide-MHC complex. This mechanism prevents the potential presentation of peptides derived from self within the context of TLR-induced co-stimulatory signals. PMID- 17284173 TI - Effect of neurotrophin-3 on reinnervation of the larynx using the phrenic nerve transfer technique. AB - Current techniques for reinnervation of the larynx following recurrent laryngeal nerve (RLN) injury are limited by synkinesis, which prevents functional recovery. Treatment with neurotrophins (NT) may enhance nerve regeneration and encourage more accurate reinnervation. This study presents the results of using the phrenic nerve transfer method, combined with NT-3 treatment, to selectively reinnervate the posterior cricoarytenoid (PCA) abductor muscle in a pig nerve injury model. RLN transection altered the phenotype and morphology of laryngeal muscles. In both the PCA and thyroarytenoid (TA) adductor muscle, fast type myosin heavy chain (MyHC) protein was decreased while slow type MyHC was increased. These changes were accompanied with a significant reduction in muscle fibre diameter. Following nerve repair there was a progressive normalization of MyHC phenotype and increased muscle fibre diameter in the PCA but not the TA muscle. This correlated with enhanced abductor function indicating the phrenic nerve accurately reinnervated the PCA muscle. Treatment with NT-3 significantly enhanced phrenic nerve regeneration but led to only a small increase in the number of reinnervated PCA muscle fibres and minimal effect on abductor muscle phenotype and morphology. Therefore, work exploring other growth factors, either alone or in combination with NT-3, is required. PMID- 17284175 TI - Engineered expression of polysialic acid enhances Purkinje cell axonal regeneration in L1/GAP-43 double transgenic mice. AB - Purkinje axons in adult mammals are generally unable to regenerate after axotomy. Our recent work has shown that over-expression of growth related genes, GAP-43 and L1, in Purkinje cells increased their axonal outgrowth into a predegenerated peripheral nerve graft, but not into a fresh graft [Zhang et al., (2005) Proc. Natl Acad. Sci. USA, 102, 14883-14888]. In the current study we investigated whether engineered expression of growth permissive molecule polysialic acid (PSA) in the glial scar or on transplanted Schwann cells could overcome the inhibitory environment and promote Purkinje axonal regeneration. A stab wound was introduced in the cerebellum of the L1/GAP-43 transgenic mice and a lentiviral vector (LV) carrying the polysialyltransferase (PST) cDNA (LV/PST) was injected into the lesion site to transduce the cells in the glial scar. Regenerating Purkinje axons were examined by calbindin immunostaining. There was increased Purkinje axonal sprouting in the area expressing high-level PSA. However, Purkinje axons were unable to grow into the lesion cavity. In the second set of experiments when LV/PST transduced Schwann cells were transplanted into the lesion site, the number of Purkinje axons growing into the transplant was nine times more than that growing into Schwann cell transplant expressing GFP two months post operation. Our result suggests that transplanted Schwann cells engineered to express PSA support axonal regeneration better than naive Schwann cells. PMID- 17284176 TI - The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats. AB - Studies of spinal cord injury using contusion (impact) injury paradigms have shown that neuronal death is an acute event that is largely over within 24 h. However, much less is known about cell death following compression injury, despite compression being a key component of natural spinal injuries. We have therefore used neuronal nuclei (NeuN) immunostaining to examine the spatiotemporal pattern of neuronal loss after static compression injury in adult rats. 3D reconstruction was used to reveal the full effect of the injury. Neuronal loss at the injury epicentre, assessed by NeuN immunostaining, amounted to 44% at 1 day but increased to 73% at 3 days and 81% at 1 month. Neuronal loss was also seen 5 mm rostral and caudal to the epicentre, but was not significant until 3 days. NeuN loss was greatest in the ventral horns and in the intermediate grey matter, with the lateral dorsal horns relatively spared. Cystic cavities formed after injury, but were not evident until 4 weeks and were small in size. In contrast to the slow profile of neuronal loss, the compression injury also evoked a transient expression of activating transcription factor-3 (ATF3) and activated c-Jun in neurons. ATF3 expression peaked at 3 days and declined at 7 days. Our spatiotemporal analysis of compression injury shows that neuronal loss is much more protracted than in contusion injury, and highlights the potential for neuroprotective strategies. This study is also the first indication of ATF3 involvement in spinal cord injury. PMID- 17284174 TI - Local synthesis of axonal and presynaptic RNA in squid model systems. AB - The presence of active systems of protein synthesis in axons and nerve endings raises the question of the cellular origin of the corresponding RNAs. Our present experiments demonstrate that, besides a possible derivation from neuronal cell bodies, axoplasmic RNAs originate in periaxonal glial cells and presynaptic RNAs derive from nearby cells, presumably glial cells. Indeed, in perfused squid giant axons, delivery of newly synthesized RNA to the axon perfusate is strongly stimulated by axonal depolarization or agonists of glial glutamate and acetylcholine receptors. Likewise, incubation of squid optic lobe slices with [3H]uridine leads to a marked accumulation of [3H]RNA in the large synaptosomes derived from the nerve terminals of retinal photoreceptor neurons. As the cell bodies of these neurons lie outside the optic lobe, the data demonstrate that presynaptic RNA is locally synthesized, presumably by perisynaptic glial cells. Overall, our results support the view that axons and presynaptic regions are endowed with local systems of gene expression which may prove essential for the maintenance and plasticity of these extrasomatic neuronal domains. PMID- 17284177 TI - Prenatal exposure to polybrominated diphenylether 99 enhances the function of the glutamate-nitric oxide-cGMP pathway in brain in vivo and in cultured neurons. AB - Polybrominated diphenylethers (PBDEs) are widely used as flame retardants. Significant amounts of PBDEs are present in the milk of lactating women. The possible neurotoxic effects of PBDEs are not well known. Perinatal exposure to PBDEs affects both motor and cognitive functions by mechanisms that remain unclear. Some types of learning depend on N-methyl-D-aspartate receptor activation, which increases intracellular calcium that binds to calmodulin and activates nitric oxide synthase, increasing nitric oxide formation that activates guanylate cyclase, increasing cGMP formation. Part of this cGMP is released to the extracellular fluid. We studied whether prenatal exposure of rats to PBDE99 alters the function of this glutamate-nitric oxide-cGMP pathway in rat brain in vivo. At 10 weeks of age, rats treated with PBDE99 showed increased function of the glutamate-nitric oxide-cGMP pathway in brain in vivo, as assessed by microdialysis in freely moving rats. The increased function of the pathway was reproduced in primary cultures of cerebellar neurons prepared from rats prenatally exposed to PBDE99 as well as in neurons cultured from normal rats and treated in vitro with PBDE99. Increased calmodulin content and activation of soluble guanylate cyclase by nitric oxide contributed to the increased function of the pathway. PMID- 17284178 TI - In vivo administration of epidermal growth factor and its homologue attenuates developmental maturation of functional excitatory synapses in cortical GABAergic neurons. AB - The ErbB1 ligand family includes epidermal growth factor (EGF), transforming growth factor-alpha (TGFalpha), heparin-binding EGF-like growth factor, amphiregulin and betacellulin. Previously, we demonstrated that TGFalpha decreases alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors in cultured neocortical gamma-aminobutyric acid (GABA) neurons. In the present study, we examined in vivo effects of EGF and TGFalpha in the mouse neocortex using electrophysiological and biochemical techniques. In mouse neonates, subcutaneously administered EGF penetrated the blood-brain barrier and activated ErbB1 in the neocortex. Daily administration of EGF or TGFalpha attenuates developmental increases in expression of the AMPA receptor subunits (GluR1 and GluR2/3) in the neocortex of postnatal mice. Immunohistochemistry revealed that the reduction in AMPA receptor expression was significant in the GABAergic neurons, especially those positive for parvalbumin. Using cortical slices prepared from EGF-treated mice, we recorded miniature excitatory postsynaptic currents (mEPSCs) in both GABAergic and pyramidal neurons. Subchronic treatment with EGF decreased the amplitude and frequency of mEPSCs in GABAergic neurons, but its effects were negligible on pyramidal neurons. We conclude that EGF or other ErbB1 ligand(s) attenuates a developmental increase in AMPA receptor expression and function in cortical GABAergic neurons. PMID- 17284179 TI - JNK1 contributes to metabotropic glutamate receptor-dependent long-term depression and short-term synaptic plasticity in the mice area hippocampal CA1. AB - Several recent reports implicate an important role played by c-Jun N-terminal kinases (JNKs) in long-term potentiation (LTP). However, little is known about how the isoforms of JNKs participate in synaptic plasticity. Here we showed that short-term synaptic plasticity was impaired in the hippocampal area CA1 of JNK1 deficient (JNK1-/-) mice; these mice showed normal LTP in response to a strong tetanus and no alteration of N-methyl-D-aspartate receptor-dependent long-term depression (LTD) in the hippocampus. However, LTD induced either by group I metabotropic glutamate receptors (mGluRs) agonist dihydroxyphenylglycine or by paired-pulse low-frequency stimulation was absent in both the JNK1-/- slices and in JNK inhibitor anthrax [1, 9-cd] pyrazol-6(2H)-1 (SP600125)-pretreated slices. Induction of mGluR-dependent LTD resulted in an increase in phosphorylation of JNK1 substrates, including p-c-Jun and p-ATF2 in wild-type (WT) mice, and these increases failed to occur in the JNK1-/- or SP600125-pretreated mice. These results demonstrated that JNK1 played a crucial role in the short-term synaptic plasticity and mGluR-dependent LTD, whereas hippocampus LTP was not affected by JNK1 deficiency. PMID- 17284180 TI - Time-course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6-hydroxydopamine in the rat: new clues from an old model. AB - Despite the progressive development of innovative animal models for Parkinson's disease, the intracerebral infusion of neurotoxin 6-hydroxydopamine (6-OHDA) remains the most widely used means to induce an experimental lesion of the nigrostriatal pathway in the animal, due to its relatively low complexity and cost, coupled with the high reproducibility of the lesion obtained. To gain new information from such a classic model, we studied the time-course of the nigrostriatal damage, metabolic changes in the basal ganglia nuclei (cytochrome oxidase activity) and behavioural modifications (rotational response to apomorphine) following unilateral injection of 6-OHDA into the corpus striatum of rat, over a 4-week period. Striatal infusion of 6-OHDA caused early damage of dopaminergic terminals, followed by a slowly evolving loss of dopaminergic cell bodies in the substantia nigra pars compacta, which became apparent during the second week post-injection and peaked at the 28th day post-infusion; the rotational response to apomorphine was already present at the first time point considered (Day 1), and remained substantially stable throughout the 4-week period of observation. The evolution of the nigrostriatal lesion was accompanied by complex changes in the metabolic activity of the other basal ganglia nuclei investigated (substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and subthalamic nucleus), which led, ultimately, to a generalized, metabolic hyperactivity, ipsilaterally to the lesion. However, peculiar patterns of metabolic activation, or inhibition, characterized the post-lesional responses of each nucleus, in the early and intermediate phases, with peculiar response profiles that varied closely related to the functional position occupied within the basal ganglia circuitry. PMID- 17284181 TI - Truncated TrkB-T1 regulates the morphology of neocortical layer I astrocytes in adult rat brain slices. AB - By altering their morphology, astrocytes, including those involved in the maintenance and plasticity of neurons and in clearance of transmitter, play important roles in synaptic transmission; however, the mechanism that regulates the morphological plasticity of astrocytes remains unclear. Recently, we reported that T1, a subtype of TrkB (a family of BDNF-specific receptors), altered astrocytic morphology through the control of Rho GTPases in primary astrocyte cultures. In this study, we extended this observation to investigate acute neocortical slices from adult rats. T1 siRNA-expression vectors were electroporated into astrocytes in neocortical layer I of living rats. In both normal slices and control vector-electroporated slices, BDNF induced the elongation of the astrocytic processes and increased the branching of processes in slices after 1 h incubation. In contrast, in T1 siRNA-electroporated slices, no such significant morphological changes were observed in the astrocytes. In addition, the number of synaptophysin+ sites in contact with GFAP+ processes increased in a BDNF-T1-dependent manner without the increase in the total synaptophysin+ sites. Therefore, the present study provides evidence of the regulation of layer I astrocytic morphology by the BDNF-T1 signal in adult rat neocortical slices. PMID- 17284182 TI - A different regional response by mouse oligodendrocyte progenitor cells (OPCs) to high-dose X-irradiation has consequences for repopulating OPC-depleted normal tissue. AB - This study was designed to investigate whether the residual, dysfunctional oligodendrocyte progenitor cells (OPCs) observed following X-irradiation of the mouse spinal cord [D. M. Chari et al. (2003) Exp. Neurol., 198, 145-153], the presence of which prevented the endogenous repopulation of these areas from normal tissue, reflects a general response of OPCs in the mouse central nervous system (CNS) to X-irradiation. The brains of adult mice were exposed to 40 Gy of X-irradiation and the effect of X-irradiation on the OPCs was assessed up to 4 weeks post-irradiation using anti-NG2 antibodies. X-irradiation resulted in almost complete depletion of OPCs within the telencephalon (cortex, corpus callosum and hippocampus) by 7 days post-irradiation, which was followed by progressive repopulation of OPCs from non-irradiated areas of the cortex. By contrast, within the lower brain centres (the diencephalon and mesencephalon) OPC loss occurred much more slowly so that 26% of the OPCs still remained 4 weeks after X-irradiation. The consequence of this heterogeneous response to X irradiation was that whereas transplanted and endogenous OPCs rapidly established themselves in the OPC-depleted telencephalon this did not occur in the areas where there was incomplete depletion of endogenous OPCs. Our findings confirm not only the requirement for almost complete OPC depletion in order to establish transplanted OPCs in normal tissue but also highlight a heterogeneity of progenitor populations in different areas of the mouse CNS. PMID- 17284184 TI - Omega-conotoxin CVIB differentially inhibits native and recombinant N- and P/Q type calcium channels. AB - Omega-conotoxins are routinely used as selective inhibitors of different classes of voltage-gated calcium channels (VGCCs) in excitable cells. In the present study, we examined the potent N-type VGCC antagonist omega-conotoxin CVID and non selective N- and P/Q-type antagonist CVIB for their ability to block native VGCCs in rat dorsal root ganglion (DRG) neurons and recombinant VGCCs expressed in Xenopus oocytes. Omega-conotoxins CVID and CVIB inhibited depolarization activated whole-cell VGCC currents in DRG neurons with pIC50 values of 8.12 +/- 0.05 and 7.64 +/- 0.08, respectively. Inhibition of Ba2+ currents in DRG neurons by CVID (approximately 66% of total) appeared to be irreversible for > 30 min washout, whereas Ba2+ currents exhibited rapid recovery from block by CVIB (> or = 80% within 3 min). The recoverable component of the Ba2+ current inhibited by CVIB was mediated by the N-type VGCC, whereas the irreversibly blocked current (approximately 22% of total) was attributable to P/Q-type VGCCs. Omega-conotoxin CVIB reversibly inhibited Ba2+ currents mediated by N- (Ca(V)2.2) and P/Q- (Ca(V)2.1), but not R- (Ca(V)2.3) type VGCCs expressed in Xenopus oocytes. The alpha2delta1 auxiliary subunit co-expressed with Ca(V)2.2 and Ca(V)2.1 reduced the sensitivity of VGCCs to CVIB but had no effect on reversibility of block. Determination of the NMR structure of CVIB identified structural differences to CVID that may underlie differences in selectivity of these closely related conotoxins. Omega-conotoxins CVIB and CVID may be useful as antagonists of N- and P/Q-type VGCCs, particularly in sensory neurons involved in processing primary nociceptive information. PMID- 17284185 TI - A postsynaptic negative feedback mediated by coupling between AMPA receptors and Na+-activated K+ channels in spinal cord neurones. AB - Na+-activated K+ channels (K(Na)) exist in different types of neurones and their activation has been shown to depend on Na+ influx via voltage-activated channels. However, one major route for Na+ influx into neurones is through ionotropic receptors and its role in activating K(Na) is still unclear. We have examined whether Na+ influx induced by activation of AMPA receptors can activate K(Na) in lamprey spinal cord neurones. Our results showed that the application of AMPA induced not only the characteristic inward current but also produced an outward current outlasting the activation of the receptors. This outward current was mediated by K+ and was abolished when Na+ was substituted with Li+. The AMPA mediated K(Na) current was completely blocked by quinidine but was not modulated by increased intracellular Cl- concentration or ATP. Thus, Na+ influx via AMPA receptor channels activates K(Na) with properties similar to Slack channels. The AMPA-activated K(Na) may act as an inherent negative feedback mechanism to regulate the homeostasis of excitation. PMID- 17284186 TI - Early electrophysiological abnormalities in lumbar motoneurons in a transgenic mouse model of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis is a lethal, adult-onset disease characterized by progressive degeneration of motoneurons. Recent data have suggested that the disease could be linked to abnormal development of the motor nervous system. Therefore, we investigated the electrical properties of lumbar motoneurons in an in-vitro neonatal spinal cord preparation isolated from SOD1(G85R) mice, which is a transgenic model of amyotrophic lateral sclerosis. The study was performed on young animals at the beginning of their second week, between postnatal days 6 and 10. Measurements of resting membrane potential and action potential characteristics of motoneurons were similar in wild-type and SOD1(G85R) mice. However, the input resistance of motoneurons from transgenic mice was significantly lower than that of wild-type animals, whereas their membrane capacitance was increased, strongly suggesting larger SOD1(G85R) motoneurons. Furthermore, the slope of the frequency-intensity curve was steeper in motoneurons from wild-type pups. Interestingly, the input resistance as well as the slope of the frequency-intensity curves of other spinal neurons did not show such differences. Finally, the amplitude of dorsal root-evoked potentials following high-intensity stimulation was significantly smaller in SOD1(G85R) motoneurons. The superoxide dismutase 1 mutation thus induces specific alterations of the functional properties of motoneurons early in development. PMID- 17284183 TI - Prokineticin 2 depolarizes paraventricular nucleus magnocellular and parvocellular neurons. AB - Blind whole-cell patch-clamp techniques were used to examine the effects of prokineticin 2 (PK2) on the excitability of magnocellular (MNC), parvocellular preautonomic (PA), and parvocellular neuroendocrine (NE) neurons within the hypothalamic paraventricular nucleus (PVN) of the rat. The majority of MNC neurons (76%) depolarized in response to 10 nm PK2, effects that were eliminated in the presence of tetrodotoxin (TTX). PK2 also caused an increase in excitatory postsynaptic potential (EPSP) frequency, a finding that was confirmed by voltage clamp recordings demonstrating increases in excitatory postsynaptic current (EPSC) frequency. The depolarizing effects of PK2 on MNC neurons were also abolished by kynurenic acid (KA), supporting the conclusion that the effects of PK2 are mediated by the activation of glutamate interneurons within the hypothalamic slice. PA (68%) and NE (67%) parvocellular neurons also depolarized in response to 10 nm PK2. However, in contrast to MNC neurons, these effects were maintained in TTX, indicating that PK2 directly affects PA and NE neurons. PK2 induced depolarizations observed in PA and NE neurons were found to be concentration-related and receptor mediated, as experiments performed in the presence of A1MPK1 (a PK2 receptor antagonist) abolished the effects of PK2 on these subpopulations of neurons. The depolarizing effects of PK2 on PA and NE neurons were also shown to be abolished by PD 98059 (a mitogen activated protein kinase (MAPK) inhibitor) suggesting that PK2 depolarizes PVN parvocellular neurons through a MAPK signalling mechanism. In combination, these studies have identified separate cellular mechanisms through which PK2 influences the excitability of different subpopulations of PVN neurons. PMID- 17284187 TI - Early functional development of interneurons in the zebrafish olfactory bulb. AB - In the adult olfactory bulb (OB) of vertebrates, local GABAergic interneurons (INs) mediate recurrent and lateral inhibition between the principal neurons of the OB, the mitral cells (MCs), and play pivotal roles in the processing of odor evoked activity patterns. The properties and functions of INs in the developing OB are, however, not well understood. We studied the functional development of INs in the OB of living zebrafish larvae 3-6 days postfertilization using anatomical techniques and in-vivo two-photon Ca2+ imaging. We identified MCs and INs by cell-type-specific expression of transgenic fluorescent markers and found that the IN:MC ratio was lower than in the adult fish. Moreover, the fraction of INs responding with Ca2+ signals to a set of natural odors was substantially lower than in adults. Odors of different chemical classes evoked overlapping patterns of Ca2+ signals that were concentrated in the center of the IN layer. The GABA(A) receptor agonists GABA and muscimol strongly suppressed odor responses, whereas a GABA(A) receptor antagonist enhanced responses and altered the spatial distribution of odor-evoked activity. These results indicate that IN odor responses at early developmental stages are sparse and exhibit no obvious chemotopic organization. Nevertheless, GABAergic signaling is already inhibitory at early stages of OB development and strongly influences odor-evoked activity patterns. Hence, INs already participate in the processing of odor information at very early stages of OB development even though the majority of INs emerge only at later stages. PMID- 17284188 TI - A nonopioid analgesic acts upon the PAG-RVM axis to reverse inflammatory hyperalgesia. AB - Metamizol (dipyrone) and other nonsteroidal anti-inflammatory drugs (NSAIDs) induce antinociception by acting upon peripheral tissues and upon central nervous system structures, notably the periaqueductal grey matter (PAG) and the spinal cord. Inflammation-induced hyperalgesia is prevented by spinal application of NSAIDs before the inflammation, but once central sensitization is established the spinal effect of NSAIDs is uncertain. The present study examines whether the action upon the PAG contributes to the attenuation of inflammation-induced spinal hyperalgesia by NSAIDs. In deeply anaesthetized rats, responses of spinal multireceptive neurons to mechanical stimulation of the ipsilateral paw and leg were recorded. An inflammation in the paw was induced with carrageenan. Fifty minutes later, neuronal responses to innocuous and noxious stimulation had, respectively, increased to 206 and 304% for paw, and 160 and 190% for leg. When metamizol (150 microg in 0.5 microL) was microinjected into PAG before the inflammation, neuronal hyperexcitability was delayed for approximately 60 min and was much reduced by 215 min. More interestingly, microinjection of metamizol into PAG when hyperexcitability was fully developed depressed neuronal responses down to baseline for approximately 1 h. The effect of PAG metamizol was reversed by microinjection of a GABA(A) agonist into the rostral ventromedial medulla (RVM), which indicates that RVM relays the metamizol effect from PAG onto the spinal cord. These results suggest that, upon clinical administration of NSAIDs, a joint action upon PAG and spinal cord contributes to preventing the development of hyperalgesia but it is mainly the action upon PAG which contributes to reducing fully established hyperalgesia. PMID- 17284190 TI - Melatonin induces gene-specific effects on rhythmic mRNA expression in the pars tuberalis of the Siberian hamster (Phodopus sungorus). AB - In mammals, circadian and photoperiodic information is encoded in the pineal melatonin signal. The pars tuberalis (PT) of the pituitary is a melatonin target tissue, which transduces photoperiodic changes and drives seasonal changes in prolactin secretion from distal lactotroph cells. Measurement of photoperiodic time in the PT is believed to occur through melatonin dependent changes in clock gene expression, although it is unclear whether the PT should be considered a melatonin sensitive peripheral oscillator. We tested this hypothesis in the Siberian hamster (Phodopus sungorus) firstly by investigating the effects of melatonin injection, and secondly by determining whether temporal variation in gene expression within the PT persists in the absence of a rhythmic melatonin signal. Hamsters preconditioned to long days were treated with melatonin during the late light phase, to advance the timing of the nocturnal melatonin peak, or placed in constant light for one 24 h cycle, thereby suppressing endogenous melatonin secretion. Gene expression in the PT was measured by in situ hybridization. We show that melatonin rapidly induces cry1 mRNA expression without the need for a prolonged melatonin-free interval, acutely inhibits mt1 expression, advances the timing of peak rev-erb alpha expression and modulates per1 expression. With the exception of cry1, these genes continue to show temporal changes in expression over a first cycle in the absence of a melatonin signal. Our data are consistent with the hypothesis that the hamster PT contains a damped endogenous circadian oscillator, which requires a rhythmic melatonin signal for long-term synchronization. PMID- 17284189 TI - Neuromodulatory effects of gonadotropin-releasing hormone on retinotectal synaptic transmission in the optic tectum of rainbow trout. AB - Gonadotropin-releasing hormone (GnRH) is a hypophysiotropic decapeptide that stimulates the release of gonadotropins from the pituitary. In addition, there are extra-hypothalamic GnRH neurons that project to all regions of the brain and whose function remains unknown. Here, we investigated the effects of GnRH on retinotectal synaptic transmission, the synapses of which are formed between retinal fibers and tectal periventricular neurons that express GnRH receptor mRNA. We used rainbow trout as our study model. The excitatory postsynaptic currents (EPSCs), which were evoked by electrical stimulation of the retinal fibers and recorded in periventricular neurons, were suppressed by antagonists of ionotropic glutamate receptors. EPSCs were increased by application of each of two types of GnRH (GnRH2 and GnRH3) in the trout tectum. Such facilitation lasted for at least 10 min after application of the GnRH. To our knowledge, this is the first report of GnRH modulating conventional synaptic transmission in the brain, suggesting that tectal GnRH enhances tectal sensitivity for retinal inputs. Furthermore, such long-lasting facilitation might occur across all the brain regions innervated by GnRH neurons, and GnRH might simultaneously switch neuronal activities in the brain regions relevant to reproductive behaviors. PMID- 17284191 TI - Selectivity of human retinotopic visual cortex to S-cone-opponent, L/M-cone opponent and achromatic stimulation. AB - Our aim was to make a quantitative comparison of the response of the different visual cortical areas to selective stimulation of the two different cone-opponent pathways [long- and medium-wavelength (L/M)- and short-wavelength (S)-cone opponent] and the achromatic pathway under equivalent conditions. The appropriate stimulus-contrast metric for the comparison of colour and achromatic sensitivity is unknown, however, and so a secondary aim was to investigate whether equivalent fMRI responses of each cortical area are predicted by stimulus contrast matched in multiples of detection threshold that approximately equates for visibility, or direct (cone) contrast matches in which psychophysical sensitivity is uncorrected. We found that the fMRI response across the two colour and achromatic pathways is not well predicted by threshold-scaled stimuli (perceptual visibility) but is better predicted by cone contrast, particularly for area V1. Our results show that the early visual areas (V1, V2, V3, VP and hV4) all have robust responses to colour. No area showed an overall colour preference, however, until anterior to V4 where we found a ventral occipital region that has a significant preference for chromatic stimuli, indicating a functional distinction from earlier areas. We found that all of these areas have a surprisingly strong response to S-cone stimuli, at least as great as the L/M response, suggesting a relative enhancement of the S-cone cortical signal. We also identified two areas (V3A and hMT+) with a significant preference for achromatic over chromatic stimuli, indicating a functional grouping into a dorsal pathway with a strong magnocellular input. PMID- 17284192 TI - Pigmentation predicts the shift in the line of decussation in humans with albinism. AB - In albinism a large proportion of nerve fibres originating in temporal retina cross the midline at the chiasm and project to the contralateral hemisphere. Studies in rodents with albinism have suggested that the extent of this misrouting at the chiasm is inversely related to pigmentation levels. Here, we examine whether there is evidence for a similar relationship in humans with albinism. Functional MRI was performed on 18 subjects with albinism, 17 control subjects and six controls with nystagmus as they underwent hemifield visual stimulation of nasal or temporal retina. Functional activation in 16 coronal slices beginning at the posterior occipital lobes were analysed and the extent of hemispheric response lateralization at each slice position was determined. During temporal retina stimulation, the control response was lateralized to the hemisphere ipsilateral to the stimulated eye for all slices. In albinos, the response in posterior slices was predominantly in the contralateral hemisphere, consistent with misrouting of temporal retina fibres. However, as slice location became progressively anterior, response lateralization reverted to the ipsilateral hemisphere. The slice location at which the transition from contra- to ipsilateralization occurred provided an estimate of the extent of fibre misrouting in the individual. The slice transition location correlated negatively with pigmentation level, providing the first evidence for a relationship between pigmentation and the extent of misrouting in humans with albinism. PMID- 17284194 TI - Enhanced synaptic excitation-inhibition ratio in hippocampal interneurons of rats with temporal lobe epilepsy. AB - A common feature of all epileptic syndromes is the repetitive occurrence of pathological patterns of synchronous neuronal activity, usually combined with increased neuronal discharge rates. Inhibitory interneurons of the hippocampal formation control both neuronal synchronization as well as the global level of activity and are therefore of crucial importance for epilepsy. Recent evidence suggests that changes in synaptic inhibition during temporal lobe epilepsy are rather specific, resulting from selective death or alteration of interneurons in specific hippocampal layers. Hence, epilepsy-induced changes have to be analysed separately for different types of interneurons. Here, we focused on GABAergic neurons located at the border between stratum radiatum and stratum lacunosum moleculare of hippocampal area CA1 (SRL interneurons), which are included in feedforward inhibitory circuits. In chronically epileptic rats at 6-8 months after pilocarpine-induced status epilepticus, frequencies of spontaneous and miniature inhibitory postsynaptic currents were reduced, yielding an almost three fold increase in excitation-inhibition ratio. Consistently, action potential frequency of SRL interneurons was about two-fold enhanced. Morphological alterations of the interneurons indicate that these functional changes were accompanied by remodelling of the local network, probably resulting in a loss of functional inhibitory synapses without conceivable cell death. Our data indicate a strong increase in activity of interneurons in dendritic layers of the chronically epileptic CA1 region. This alteration may enhance feedforward inhibition and rhythmogenesis and--together with specific changes in other interneurons--contribute to seizure susceptibility and pathological synchronization. PMID- 17284193 TI - Developmental divergence of sleep-wake patterns in orexin knockout and wild-type mice. AB - Narcolepsy, a disorder characterized by fragmented bouts of sleep and wakefulness during the day and night as well as cataplexy, has been linked in humans and nonhuman animals to the functional integrity of the orexinergic system. Adult orexin knockout mice and dogs with a mutation of the orexin receptor exhibit symptoms that mirror those seen in narcoleptic humans. As with narcolepsy, infant sleep-wake cycles in humans and rats are highly fragmented, with consolidated bouts of sleep and wakefulness developing gradually. Based on these common features of narcoleptics and infants, we hypothesized that the development of sleep-wake fragmentation in orexin knockout mice would be expressed as a developmental divergence between knockouts and wild-types, with the knockouts lagging behind the wild-types. We tested this hypothesis by recording the sleep wake patterns of infant orexin knockout and wild-type mice across the first three postnatal weeks. Both knockouts and wild-types exhibited age-dependent, and therefore orexin-independent, quantitative and qualitative changes in sleep-wake patterning. At 3 weeks of age, however, by which time the sleep and wake bouts of the wild-types had consolidated further, the knockouts lagged behind the wild types and exhibited significantly more bout fragmentation. These findings suggest the possibility that the fragmentation of behavioural states that characterizes narcolepsy in adults reflects reversion back toward the more fragmented sleep wake patterns that characterize infancy. PMID- 17284195 TI - Differential effects of NT-4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical period. AB - Development of inhibition is a crucial determinant of the time course of visual cortical plasticity. BDNF strongly affects interneuron development and the onset and closure of the critical period for ocular dominance plasticity. Less is known on the effects of NT-4 despite a clear involvement in ocular dominance plasticity. We have investigated the effects of NT-4 on interneuron development by supplying NT-4 with osmotic minipumps during two time windows overlapping the onset (P12-20) and the peak (P20-28) of the critical period. We assessed the expression of interneuronal markers and soma size maturation either after the end of the infusion periods or at the end of the critical period (P45). We found that NT-4 was very effective in regulating interneuron development. NPY, SOM and PARV neuron somata grew faster during both infusion periods whereas CR neurons only responded during the early infusion period. The effects of soma size elicited during the earlier infusion period were still present at P45. In PARV neurons, NT 4 caused a long-lasting stabilization of CB and NPY expression. Furthermore, NT-4 accelerated the expression of GAD-65 mRNA in a subset of non-PARV neurons of layer V, which normally up-regulate GAD-65 towards the end of the critical period. Most of these effects were shared by NT-4 and BDNF. Some were unexpectedly also shared by NGF, which promoted growth of layer V PARV neurons, stabilized the CB expression and accelerated the GAD-65 expression. The results suggest that neurotrophins act on critical period plasticity by strengthening inhibition. PMID- 17284196 TI - Intermittent ethanol exposure induces inflammatory brain damage and causes long term behavioural alterations in adolescent rats. AB - Adolescent brain development seems to be important for the maturation of brain structures and behaviour. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage. Because we have demonstrated that chronic ethanol treatment induces inflammatory processes in the brain, we investigate whether intermittent ethanol intoxication enhances cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in adolescent rats, and whether these mediators induce brain damage and cause permanent cognitive dysfunctions. Adolescent rats were exposed to ethanol (3.0 g/kg) for two consecutive days at 48-h intervals over 14 days. Levels of COX-2, iNOS and cell death were assessed in the neocortex, hippocampus and cerebellum 24 h after the final ethanol administration. The following day or 20 days after the final injection (adult stage), animals were tested for different behavioural tests (conditional discrimination learning, rotarod, object recognition, beam-walking performance) to assess cognitive and motor functions. Our results show that intermittent ethanol intoxication upregulates COX-2 and iNOS levels, and increases cell death in the neocortex, hippocampus and cerebellum. Furthermore, animals treated with ethanol during adolescence exhibited behavioural deficits that were evident at the end of ethanol treatments and at the adult stage. Administration of indomethacin, a COX-2 inhibitor, abolishes the induction of COX 2 and iNOS expression and cell death, preventing ethanol-induced behavioural deficits. These findings indicate that binge pattern exposure to ethanol during adolescence induces brain damage by inflammatory processes and causes long lasting neurobehavioural consequences. Accordingly, administering indomethacin protects against ethanol-induced brain damage and prevents detrimental ethanol effects on cognitive and motor processes. PMID- 17284197 TI - The operant serial implicit learning task reveals early onset motor learning deficits in the Hdh knock-in mouse model of Huntington's disease. AB - A range of genetic mouse models of Huntington's disease have been created. However, as knock-in models typically have milder phenotypes, they have frequently been overlooked as therapeutic tools in favour of the transgenic models that display severe behavioural symptoms. More sensitive tests are therefore required to reveal abnormalities and release the potential of knock-in lines. An implicit learning task for mice has been developed in the nine-hole operant box test apparatus, in which mice must respond to a sequence of lights in order to earn a reward. A light stimulus was presented randomly in one of five holes, to which a nose poke response resulted in the light being extinguished and a second light illuminated in a different hole. Response to the second light resulted in a liquid reward. To probe implicit learning, a predictable stimulus sequence was embedded among many unpredictable sequences. In the current study, the Hdh(Q92) mouse model of Huntington's disease was examined. At 4 months of age, Hdh(Q92/Q92) mice demonstrated clear and significant deficits in both accuracy and reaction time on all trials of the implicit learning task, with improved performance on predictable trials. We believe this to be the earliest reported behavioural deficit in the Hdh(Q92) knock-in mouse line. The results of this study validate the serial implicit learning task as a sensitive tool for the examination of implicit and motor learning deficits in mutant mice, and may provide a powerful test for probing potential treatments for Huntington's disease. PMID- 17284198 TI - Inactivation of the prelimbic, but not infralimbic, prefrontal cortex impairs the contextual control of response conflict in rats. AB - One fundamental function of the prefrontal cortex (PFC) is to guide context appropriate behaviour in situations of response conflict. Haddon and Killcross recently developed a task in rats which mimics some aspects of response conflict seen in human cognitive paradigms such as the Stroop task. Using this paradigm they demonstrated that large PFC lesions including the prelimbic (PL), infralimbic (IL) and anterior cingulate cortices (ACC) selectively impaired performance on incongruent trials which required the use of task-setting contextual cues to control responding in the face of ambiguous response information. The current experiment was conducted to determine whether specific PFC regions were responsible for the deficit in incongruent performance. Rats were trained on two instrumental biconditional discriminations, one auditory and one visual, in two different contexts. Following acquisition, rats were implanted with guide cannulae aimed at the PL or the IL cortices of the rat prefrontal cortex. Following retraining, rats received microinfusions of the GABA(A) agonist muscimol or artificial cerebrospinal fluid (aCSF) into either the PL or the IL prior to presentations of novel congruent and incongruent audiovisual compounds of the training stimuli in extinction. Results showed that temporary inactivation of the PL cortex led to a selective deficit on incongruent compound trials, but left congruent, and hence biconditional task performance intact. By contrast, IL inactivation had no effect on the accuracy of responding during either congruent or incongruent trials. These results suggest that the PL cortex is necessary for the use of task-setting contextual cues to control responding to conflicting information. PMID- 17284199 TI - Effect of resource availability on biparental care, and offspring neural and behavioral development in the California mouse (Peromyscus californicus). AB - Maternal care influences cognitive function in humans, primates and rodents; however, little is known about the effect of biparental care. Environmental factors such as resource availability play an important role in modulating parental investment strategies with subsequent effects on the offspring. Thus, we examined the interaction between foraging demand and biparental care on hippocampal development and novel object recognition in the monogamous, biparental California mouse. We characterized biparental behavior for 15 days in families exposed to either control (ad libitum feeding) or a high-foraging demand across the weaning period. Adult male offspring were then tested in the open field, and for novel object and place recognition, as well as for hippocampal synaptic density and the expression of genes encoding for subunits of the N methyl-D-aspartate (NMDA) receptor complex, and the postsynaptic density (PSD)-95 scaffolding protein. Under high-foraging demand, the mothers' body weight was decreased at weaning and fathers spent significantly less time in contact with pups. Offspring reared under high-foraging demand weighed less at weaning and, as adults, were more fearful in the open field and showed profound deficits in both novel object and place recognition. While synaptic density and NR1 mRNA expression were unaffected, offspring reared under high-foraging demand showed increased NR2A and decreased NR2B mRNA expression. Further, PSD-95 protein expression was decreased in mice reared under high-foraging demand. Together, the results suggest that resource availability affects biparental investment strategies, with subsequent effects on hippocampal development and novel object recognition in the offspring. PMID- 17284201 TI - Dissociation of sustained attention from central executive functions: local activity and interregional connectivity in the theta range. AB - Human brain oscillatory activity was analysed in the electroencephalographic theta frequency range (4-7 Hz) while subjects executed complex sequential finger movements with varying task difficulty and memory load. Local frontal-midline theta activity was associated with the general level of cognitive demand, with the highest amplitudes in the most demanding condition. Using low-resolution electromagnetic tomography analysis (LORETA), this theta activity was localized in the anterior cingulate gyrus including the cingulate motor area. These results suggest that local theta activity in the anterior cingulate gyrus represents correlates of an attentional system that allocate cognitive resources. In addition, interregional connectivity in the theta frequency range was modulated by memory-related executive functions independently of task difficulty. Connectivity analyses revealed a more distributed long-range network including frontal and parietal cortices during execution of novel compared with well trained finger movement sequences. Thus, these results are compatible with a model in which theta long-range coupling indicates integration of sensory information into executive control components of complex motor behaviour. PMID- 17284200 TI - Binaral interaction and centrifugal input enhances spatial contrast in olfactory bulb activation. AB - We used paired-pulse odorant stimulation, with a conditioning stimulus delivered either ipsilateral or contralateral to a test stimulus, to unmask the effects of centrifugal feedback on olfactory bulb responses. In reptiles and mammals there are no direct connections between the paired olfactory bulbs, and thus all information transfer between the olfactory bulbs depends on feedback from retrobulbar structures. We measured odor-induced activity in the turtle olfactory bulb using a voltage-sensitive dye and a 464-element photodiode array, which allowed us to monitor the spatial variation in activation of the olfactory bulb. We found that both contralateral and ipsilateral conditioning stimuli evoked long lasting inhibition of olfactory bulb activation. In contrast to previous studies using local field potential recording to monitor activity at a single site, we found that this inhibition increased contrast in the spatial patterning of activation over the dorsal surface of the olfactory bulb. Inhibition was also increased when different odorants were used as conditioning and test stimuli, suggesting a role for centrifugal feedback in olfactory discrimination. These results highlight the functional importance of centrifugal feedback and information processing in a broadly distributed olfactory network. PMID- 17284202 TI - Differentiating allocation of resources and conflict detection within attentional control processing. AB - Increasing demands for conflict detection and for allocation of attentional resources increase the need for attentional control. While prior evidence suggests that different cortical regions are preferentially engaged by these two attentional processes, the effect of increasing demand for conflict detection and/or allocation of attentional resources has been relatively unexplored. We designed a novel task (the 'variable attentional control'--VAC--task) that varies the demand for attentional control by increasing conflict detection and allocation of attentional resources within the same stimuli. We studied 34 subjects who underwent event-related functional magnetic resonance imaging while performing the VAC task. Increasing demand for attentional control, as reflected by longer reaction time and reduced accuracy, was associated with greater activation in the dorsolateral prefrontal cortex, parietal cortex and dorsal cingulate. Furthermore, an increase in conflict detection was associated with greater dorsal cingulate activity, whereas an increase in demand for allocation of attentional resources implied greater activation in the dorsolateral prefrontal and parietal cortices. In essence, in addition to allowing the exploration of the overall effects of increasing demand for attentional control, our novel task also allowed parsing of the neural components of attentional control into those related to allocation of attentional resources and those related to conflict detection. PMID- 17284203 TI - Mechanisms of selective inhibition in visual spatial attention are indexed by alpha-band EEG synchronization. AB - Electroencephalographic studies in humans have demonstrated that orienting of visual attention induces a decrease in oscillatory alpha-band activity (alpha desynchronization) over cortical areas tuned to the attended visual space. This is interpreted as reflecting intentionally enhanced excitability of these areas to facilitate upcoming visual processing. However, the inverse mechanism might also apply. Brain areas that process task-irrelevant space might be actively suppressed by increased alpha-activity (alpha-synchronization) to protect against input of distracter information. In the present study, we demonstrate that such suppression mechanisms are highly selective and are taking place even without distracters that need to be ignored. During voluntary orienting of attention, we found alpha-synchronization to dominate over desynchronization, to be topographically specific for each of eight attention positions, and to occur over areas processing unattended space in a retinotopically organized pattern. This indicates that alpha-synchronization is an important component of selective attention, serving active suppression of unattended positions during visual spatial orienting. PMID- 17284204 TI - Incorporating multiple mixed stocks in mixed stock analysis: 'many-to-many' analyses. AB - Traditional mixed stock analyses use morphological, chemical, or genetic markers measured in several source populations and in a single mixed population to estimate the proportional contribution of each source to the mixed population. In many systems, however, different individuals from a particular source population may go to a variety of mixed populations. Now that data are becoming available from (meta)populations with multiple mixed stocks, the need arises to estimate contributions in this 'many-to-many' scenario. We suggest a Bayesian hierarchical approach, an extension of previous Bayesian mixed stock analysis algorithms, that can estimate contributions in this case. Applying the method to mitochondrial DNA data from green turtles (Chelonia mydas) in the Atlantic gives results that are largely consistent with previous results but makes some novel points, e.g. that the Florida, Bahamas and Corisco Bay foraging grounds have greater contributions than previously thought from distant foraging grounds. More generally, the 'many to-many' approach gives a more complete understanding of the spatial ecology of organisms, which is especially important in species such as the green turtle that exhibit weak migratory connectivity (several distinct subpopulations at one end of the migration that mix in unknown ways at the other end). PMID- 17284205 TI - Detection and visualization of spatial genetic structure in continuous Eucalyptus globulus forest. AB - Visualizing the pattern of variation using microsatellites within a Eucalyptus globulus forest on the island of Tasmania provided surprising insights into the complex nature of the fine-scale spatial genetic structure that resides in these forests. We used spatial autocorrelation and principal coordinate analysis to compare fine-scale genetic structure between juvenile and mature cohorts in a study area, 140 m in diameter, located within a typical, continuous E. globulus forest. In total, 115 juvenile and 168 mature individuals were genotyped with eight highly polymorphic microsatellite loci. There was no significant difference in the level of genetic diversity between cohorts. However, there were differences in the spatial distribution of the genetic variation. Autocorrelation analysis provided clear evidence for significant spatial genetic structure in the mature cohort and significant, but weaker, structure in the juvenile cohort. The spatial interpolation of principal coordinate axes, derived from ordination of the genetic distance matrix between individuals, revealed a spatially coherent family group which was evident in both cohorts. Direct comparison of the genetic structure within each cohort allowed visualization of a shift in the spatial distribution of genetic variation within the population of approximately 10 m. As the shift coincided with the direction of prevailing winds, it is hypothesized that this phenomenon is due to downwind dispersal of seeds and is indicative of the important role of prevailing winds in forcing eastward gene flow in these high-latitude forests. PMID- 17284206 TI - Genetic structure of the widespread and common Mediterranean bryophyte Pleurochaete squarrosa (Brid.) Lindb. (Pottiaceae) - evidence from nuclear and plastidic DNA sequence variation and allozymes. AB - The Mediterranean Basin as one the world's most biologically diverse regions provides an interesting area for the study of plant evolution and spatial structure in plant populations. The dioecious moss Pleurochaete squarrosa is a widespread and common bryophyte in the Mediterranean Basin. Thirty populations were sampled for a study on molecular diversity and genetic structure, covering most major islands and mainland populations from Europe and Africa. A significant decline in nuclear and chloroplast sequence and allozyme variation within populations from west to east was observed. While DNA sequence data showed patterns of isolation by distance, allozyme markers did not. Instead, their considerable interpopulation genetic differentiation appeared to be unrelated to geographic distance. Similar high values for coefficients of gene diversity (G(ST)) in all data sets provided evidence of geographic isolation and limited gene flow among populations (i) within islands, (ii) within mainland areas, and (iii) between islands and mainland. Notably, populations in continental Spain are strongly genetically isolated from all other investigated areas. Surprisingly, there was no difference in gene diversity and G(ST) between islands and mainland areas. Thus, we conclude that large Mediterranean islands may function as 'mainland' for bryophytes. This hypothesis and its implication for conservation biology of cryptogamic plants warrant further investigation. While sexually reproducing populations were found all over the Mediterranean Basin, high levels of multilocus linkage disequilibrium provide evidence of mainly vegetative propagation even in populations where sexual reproduction was observed. PMID- 17284207 TI - Chloroplast DNA supports a hypothesis of glacial refugia over postglacial recolonization in disjunct populations of black pine (Pinus nigra) in western Europe. AB - European black pine (Pinus nigra Arn.) is a widely distributed Mediterranean conifer. To test the hypothesis that fragmented populations in western Europe survived in situ during the last glacial rather than having been re-colonized in the postglacial period, genetic variation was assessed using a suite of 10 chloroplast DNA microsatellites. Among 311 individuals analysed, 235 haplotypes were detected revealing high levels of chloroplast haplotype diversity in most populations. Bayesian analysis using a model of linked loci, with no prior assumption of population structure, assigned individuals to 10 clusters that corresponded well with the six predefined sampling regions, while an analysis carried out at the population level and assuming unlinked loci, recovered the original six sampling regions. This regional structure was supported by a biogeographical analysis that detected five barriers, with the two most significant separating Alps from Corsica and southern Italy, and southern Spain from the Pyrenees. No signals of demographic expansion were detected, and comparisons of R(ST) with pR(ST) suggested that a stepwise mutational model was important in regional differentiation, but not in population-within-region differentiation. These tests support long-term persistence of the species within the six regions. The temporal depth estimate, assuming a high mutation rate in coalescent modelling, placed the deepest split between the Alps and the other regions at about 150 000 years ago, and the most recent split of Pyrenees from southern France at about 30 000 years ago. Taken together, the data suggest that chloroplast DNA is structured in black pine and disjunct populations in western Europe are likely to have been present during the Last Glacial Maximum. PMID- 17284208 TI - Compatible genetic and ecological estimates of dispersal rates in insect (Coenagrion mercuriale: Odonata: Zygoptera) populations: analysis of 'neighbourhood size' using a more precise estimator. AB - Genetic and demographic estimates of dispersal are often thought to be inconsistent. In this study, we use the damselfly Coenagrion mercuriale (Odonata: Zygoptera) as a model to evaluate directly the relationship between estimates of dispersal rate measured during capture-mark-recapture fieldwork with those made from the spatial pattern of genetic markers in linear and two-dimensional habitats. We estimate the 'neighbourhood size' (Nb) - the product of the mean axial dispersal rate between parent and offspring and the population density - by a previously described technique, here called the regression method. Because C. mercuriale is less philopatric than species investigated previously by the regression method we evaluate a refined estimator that may be more applicable for relatively mobile species. Results from simulations and empirical data sets reveal that the new estimator performs better under most situations, except when dispersal is very localized relative to population density. Analysis of the C. mercuriale data extends previous results which demonstrated that demographic and genetic estimates of Nb by the regression method are equivalent to within a factor of two at local scales where genetic estimates are less affected by habitat heterogeneity, stochastic processes and/or differential selective regimes. The corollary is that with a little insight into a species' ecology the pattern of spatial genetic structure provides quantitative information on dispersal rates and/or population densities that has real value for conservation management. PMID- 17284209 TI - Hierarchical components of genetic variation at a species boundary: population structure in two sympatric varieties of Lupinus microcarpus (Leguminosae). AB - Lupinus microcarpus is a self-compatible annual plant that forms a species complex of morphologically variable but indeterminate varieties. In order to examine the hypothesis that varieties of L. microcarpus comprise genetically differentiated and reproductively isolated species, populations of L. microcarpus var. horizontalis and var. densiflorus were sampled from an area of sympatry in central California and genotyped using six microsatellite loci. Bayesian clustering divided the total sample into two groups corresponding to the named varieties with extremely low levels of inferred coancestry. Similarly, maximum likelihood and distance methods for genetic assignment placed individuals in two nonoverlapping groups. Evidence for isolation by distance (IBD) within each variety was found at shorter distance classes, but varieties remained differentiated in sympatry. Furthermore, coalescent estimates of divergence time indicate separation within the past 950-5050 generations, with minimal gene flow after divergence. A four-level hierarchical analysis of molecular variance (amova) found significant levels of genetic differentiation among varieties (theta(P) = 0.292), populations within varieties (theta(S) = 0.449), subpopulations within populations (theta(SS) = 0.623), and individuals within subpopulations (f = 0.421); but the greatest degree of differentiation was at the subpopulation level. Although it is sometimes assumed that the magnitude of genetic differences (e.g. F(ST)) should be greater between species than among populations or subpopulations of the same species, shared ancestral polymorphism may lead to relatively low levels of differentiation at the species level, even as the stochastic effects of genetic drift generate higher levels of differentiation at lower hierarchical levels. These results suggest that L. microcarpus var. horizontalis and var. densiflorus are recently diverged yet reproductively isolated species, with high levels of inbreeding resulting from the combined effects of limited gene flow, demographic bottlenecks, and partial selfing in finite, geographically structured populations. PMID- 17284210 TI - Multiple scales of genetic connectivity in a brooding coral on isolated reefs following catastrophic bleaching. AB - Understanding the pattern of connectivity among populations is crucial for the development of realistic and spatially explicit population models in marine systems. Here we analysed variation at eight microsatellite loci to assess the genetic structure and to infer patterns of larval dispersal for a brooding coral, Seriatopora hystrix, at an isolated system of reefs in northern Western Australia. Spatial autocorrelation analyses show that populations are locally subdivided, and that the majority of larvae recruit to within 100 m of their natal colony. Further, a combination of F- and R- statistics showed significant differentiation at larger spatial scales (2-60 km) between sites, and this pattern was clearly not associated with distance. However, Bayesian analysis demonstrated that recruitment has been supplemented by less frequent but recent input of larvae from outside the local area; 2-6% of colonies were excluded from the site at which they were sampled. Individual assignments of these migrants to the most likely populations suggest that the majority of migrants were produced at the only site that was not decimated by a recent and catastrophic coral bleaching event. Furthermore, the only site that recovered to prebleaching levels received most of these immigrants. We conclude that the genetic structure of this brooding coral reflects its highly opportunistic life history, in which prolific, philopatric recruitment is occasionally supplemented by exogenously produced larvae. PMID- 17284211 TI - Defining population boundaries: use of three Bayesian approaches with microsatellite data from British natterjack toads (Bufo calamita). AB - Defining boundaries between populations is often difficult in the absence of information about current levels of gene flow. Such definitions can be important, however, both for the understanding of population dynamics and for conservation planning. Recently developed Bayesian methods for analysing genetic data now provide a powerful approach to this problem. Natterjack toads Bufo calamita are endangered in Britain, where their distribution is restricted to four geographically discrete regions. In three of these regions the boundaries between populations are often uncertain. We therefore used Bayesian approaches with microsatellite data to try and define British natterjack population structure, and thus inform conservation management. A large sample of natterjack toads from all 38 locations in Britain where the species is native was genotyped at eight microsatellite loci. The genetic diversity of natterjack populations declined as a function of increasing latitude, echoing postglacial colonization dynamics. Comparisons of three assignment methods (structure, baps and geneland) generated some broad similarities but also some inconsistencies in the definitions of population structure, especially in the most complex region (south Cumbria). Implications of the analyses for the future conservation of Bufo calamita in Britain are discussed. PMID- 17284212 TI - Impact of selective logging on inbreeding and gene dispersal in an Amazonian tree population of Carapa guianensis Aubl. AB - Selective logging may impact patterns of genetic diversity within populations of harvested forest tree species by increasing distances separating conspecific trees, and modifying physical and biotic features of the forest habitat. We measured levels of gene diversity, inbreeding, pollen dispersal and spatial genetic structure (SGS) of an Amazonian insect-pollinated Carapa guianensis population before and after commercial selective logging. Similar levels of gene diversity and allelic richness were found before and after logging in both the adult and the seed generations. Pre- and post-harvest outcrossing rates were high, and not significantly different from one another. We found no significant levels of biparental inbreeding either before or after logging. Low levels of pollen pool differentiation were found, and the pre- vs. post-harvest difference was not significant. Pollen dispersal distance estimates averaged between 75 m and 265 m before logging, and between 76 m and 268 m after logging, depending on the value of tree density and the dispersal model used. There were weak and similar levels of differentiation of allele frequencies in the adults and in the pollen pool, before and after logging occurred, as well as weak and similar pre- and post-harvest levels of SGS among adult trees. The large neighbourhood sizes estimated suggest high historical levels of gene flow. Overall our results indicate that there is no clear short-term genetic impact of selective logging on this population of C. guianensis. PMID- 17284213 TI - Recombination and introgression of nuclear and chloroplast genomes between the peat mosses, Sphagnum capillifolium and Sphagnum quinquefarium. AB - Haploid hybrid gametophytes are often present at low frequencies in sympatric populations of Sphagnum capillifolium and Sphagnum quinquefarium. We used intersimple sequence repeat (ISSR) markers and polymerase chain reaction restriction fragment length polymorphism of the trnL(UAA) intron of the chloroplast genome to reveal the nuclear and chloroplast composition of mature hybrid gametophytes from natural populations and of gametophytes derived from spores of hybrid sporophytes collected in nature. Asymmetrical nuclear inheritance was found in the progeny of the hybrid sporophytes, indicating that only spores with a low level of recombination of parental genomes were viable. A similarly skewed nuclear composition was found among the naturally occurring hybrid gametophytes. All hybrid genomes contained a larger proportion of S. capillifolium ISSR markers, combined with only two to five S. quinquefarium markers together with a chloroplast haplotype derived from S. quinquefarium. In this way, a pattern resembling introgression is created within a single generation. Some individuals possessed nuclear genomes typical for S. capillifolium in combination with the chloroplast haplotype of S. quinquefarium, possibly indicating backcrossing. Our results indicate that hybridization between S. capillifolium and S. quinquefarium is relatively common, but the resistance of large parts of the genome against heterospecific genes maintains the genetic distinctness of the species. Further evolutionary and phylogenetic consequences of restricted interspecific gene exchange are discussed. PMID- 17284214 TI - Phylogeography and population history of the crab-eating fox (Cerdocyon thous). AB - The crab-eating fox is a medium-sized Neotropical canid with generalist habits and a broad distribution in South America. We have investigated its genetic diversity, population structure and demographic history across most of its geographic range by analysing 512 base pairs (bp) of the mitochondrial DNA (mtDNA) control region, 615 bp of the mtDNA cytochrome b gene and 1573 total nucleotides from three different nuclear fragments. MtDNA data revealed a strong phylogeographic partition between northeastern Brazil and other portions of the species' distribution, with complete separation between southern and northern components of the Atlantic Forest. We estimated that the two groups diverged from each other c. 400,000-600,000 years ago, and have had contrasting population histories. A recent demographic expansion was inferred for the southern group, while northern populations seem to have had a longer history of large population size. Nuclear sequence data did not support this north-south pattern of subdivision, likely due at least in part to secondary male-mediated historical gene flow, inferred from multilocus coalescent-based analyses. We have compared the inferred phylogeographic patterns to those observed for other Neotropical vertebrates, and report evidence for a major north-south demographic discontinuity that seems to have marked the history of the Atlantic Forest biota. PMID- 17284215 TI - Working at the interface of phylogenetics and population genetics: a biogeographical analysis of Triaenops spp. (Chiroptera: Hipposideridae). AB - New applications of genetic data to questions of historical biogeography have revolutionized our understanding of how organisms have come to occupy their present distributions. Phylogenetic methods in combination with divergence time estimation can reveal biogeographical centres of origin, differentiate between hypotheses of vicariance and dispersal, and reveal the directionality of dispersal events. Despite their power, however, phylogenetic methods can sometimes yield patterns that are compatible with multiple, equally well supported biogeographical hypotheses. In such cases, additional approaches must be integrated to differentiate among conflicting dispersal hypotheses. Here, we use a synthetic approach that draws upon the analytical strengths of coalescent and population genetic methods to augment phylogenetic analyses in order to assess the biogeographical history of Madagascar's Triaenops bats (Chiroptera: Hipposideridae). Phylogenetic analyses of mitochondrial DNA sequence data for Malagasy and east African Triaenops reveal a pattern that equally supports two competing hypotheses. While the phylogeny cannot determine whether Africa or Madagascar was the centre of origin for the species investigated, it serves as the essential backbone for the application of coalescent and population genetic methods. From the application of these methods, we conclude that a hypothesis of two independent but unidirectional dispersal events from Africa to Madagascar is best supported by the data. PMID- 17284216 TI - Cryptic behaviours, inverse genetic landscapes, and spatial avoidance of inbreeding in the Pacific jumping mouse. AB - Although the behaviour of individuals is known to impact the genetic make-up of a population, observed behavioural patterns do not always correspond to patterns of genetic structure. In particular, philopatric or dispersal-limited species often display lower-than-expected values of relatedness or inbreeding suggestive of the presence of cryptic migration, dispersal, or mating behaviours. I used a combination of microsatellite and mark-recapture data to test for the influence of such behaviours in a dispersal-limited species, the Pacific jumping mouse, within a semi-isolated population over three seasons. Despite short dispersal distances and a low rate of first generation migrants, heterozygosities were high and inbreeding values were low. Dispersal was male-biased; interestingly however, this pattern was only present when dispersal was considered to include movement away from paternal home range. Not unexpectedly, males were polygynous; notably, some females were also found to be polyandrous, selecting multiple neighbouring mates for their single annual litter. Patterns of genetic structure were consistent with these more inconspicuous behavioural patterns. Females were more closely related than males and isolation by distance was present only in females. Furthermore, detailed genetic landscapes revealed the existence of strong, significant negative correlations, with areas of low genetic distance among females overlapping spatially with areas of high genetic distance among males. These results support the hypothesis that the detected cryptic components of dispersal and mating behaviour are reducing the likelihood of inbreeding in this population through paternally driven spatial mixing of male genotypes and polyandry of females. PMID- 17284217 TI - Global patterns of diversity and community structure in marine bacterioplankton. AB - Because of their small size, great abundance and easy dispersal, it is often assumed that marine planktonic microorganisms have a ubiquitous distribution that prevents any structured assembly into local communities. To challenge this view, marine bacterioplankton communities from coastal waters at nine locations distributed world-wide were examined through the use of comprehensive clone libraries of 16S ribosomal RNA genes, used as operational taxonomic units (OTU). Our survey and analyses show that there were marked differences in the composition and richness of OTUs between locations. Remarkably, the global marine bacterioplankton community showed a high degree of endemism, and conversely included few cosmopolitan OTUs. Our data were consistent with a latitudinal gradient of OTU richness. We observed a positive relationship between the relative OTU abundances and their range of occupation, i.e. cosmopolitans had the largest population sizes. Although OTU richness differed among locations, the distributions of the major taxonomic groups represented in the communities were analogous, and all local communities were similarly structured and dominated by a few OTUs showing variable taxonomic affiliations. The observed patterns of OTU richness indicate that similar evolutionary and ecological processes structured the communities. We conclude that marine bacterioplankton share many of the biogeographical and macroecological features of macroscopic organisms. The general processes behind those patterns are likely to be comparable across taxa and major global biomes. PMID- 17284219 TI - Divergent selection as revealed by P(ST) and QTL-based F(ST) in three-spined stickleback (Gasterosteus aculeatus) populations along a coastal-inland gradient. AB - Three measures of divergence, estimated at nine putatively neutral microsatellite markers, 14 quantitative traits, and seven quantitative trait loci (QTL) were compared in eight populations of the three-spined stickleback (Gasterosteus aculeatus L.) living in the Scheldt river basin (Belgium). Lowland estuarine and polder populations were polymorphic for the number of lateral plates, whereas upland freshwater populations were low-plated. The number of short gill rakers and the length of dorsal and pelvic spines gradually declined along a coastal inland gradient. Plate number, short gill rakers and spine length showed moderate to strong signals of divergent selection between lowland and upland populations in comparison between P(ST) (a phenotypic alternative for Q(ST)) and neutral F(ST). However, such comparisons rely on the unrealistic assumption that phenotypic variance equals additive genetic variance, and that nonadditive genetic effects and environmental effects can be minimized. In order to verify this assumption and to confirm the phenotypic signals of divergence, we tested for divergent selection at the underlying QTL. For plate number, strong genetic evidence for divergent selection between lowland and upland populations was obtained based on an intron marker of the Eda gene, of which the genotype was highly congruent with plate morph. Genetic evidence for divergent selection on short gill rakers was limited to some population pairs where F(ST) at only one of two QTL was detected as an outlier, although F(ST) at both loci correlated significantly with P(ST). No genetic confirmation was obtained for divergent selection on dorsal spine length, as no outlier F(ST)s were detected at dorsal spine QTL, and no significant correlations with P(ST) were observed. PMID- 17284218 TI - Determining the outcome of field-based competition between two Rhizopogon species using real-time PCR. AB - Interest in the ecology of ectomycorrhizal (ECM) fungi has increased considerably, but little is known about interspecific interactions among ECM species. We examined competitive interactions between Rhizopogon occidentalis and R. salebrosus at Point Reyes National Seashore, California, USA. At three field sites, species abundances were compared in single- and two-species treatments on Pinus muricata seedlings inoculated with spores. Competition for root tips was assessed using real-time polymerase chain reaction (PCR) of internal transcribed spacer rDNA. In general, we found strong competitive exclusion of R. salebrosus by R. occidentalis, with >or= 75% of the seedlings in the two-species treatment colonized exclusively by R. occidentalis after 5 and 10 months. However, on the seedlings that were co-colonized, we observed no significant difference in the abundances of R. salebrosus and R. occidentalis, suggesting that once R. salebrosus was established, it was no longer competitively inferior. There were no significant differences in survival, growth, or percentage leaf nitrogen of seedlings colonized with either Rhizopogon species, but both growth and percentage leaf nitrogen were significantly higher for ECM than non-ECM seedlings. We also observed strong positive correlations between actual ECM root tip weight and that inferred from real-time PCR for both species, indicating that this method provided an accurate assessment of root tip occupation and hence ECM competitive dynamics. In conjunction with a previous experiment, our results indicate that competition between these two Rhizopogon species occurs similarly in both field and laboratory settings and that when colonizing from spore, timing largely determines the outcome of initial competitive interactions. PMID- 17284220 TI - Characterization of a novel HLA-DRB1*04 allele (DRB1*0460) in the Italian population. AB - We report the identification of a novel HLA-DRB1*04, officially named DRB1*0460. It was detected during performing HLA-DRB1 high resolution typing by DNA sequencing-based method. The exon 2 nucleotide sequence of DRB1*0460 is identical to that of DRB1*040301 except at codon 63 (AGC-->AAC), changing the encoded serine to asparagine. PMID- 17284221 TI - A survey of H2 gene sequences, including new wild-derived genes. AB - A comprehensive collection of mouse major histocompatibility complex (MHC) promoter and exon 2 sequences is here presented and analysed. It covers the three best known class II genes and one class I gene, and includes new wild mouse sequences from the 'w' back-cross strains and from the Jackson collection. All sequences are in GenBank, and the new exon sequences largely confirm previous typing by serology and immune function. As in human leucocyte antigen (HLA), the overall nucleotide diversity is higher in the class II genes, in keeping with their more diverse function. Diversity along the promoters is highest in the region of known transcription factor binding, most notably in and around the CRE and rCAAT sequences. This distribution parallels that of maximum single nucleotide polymorphism impact previously obtained with reporter constructs. Taking into account the low nucleotide diversity of the CIITA promoter, we conclude that MHC promoters are likely to have diversified through co-evolution with their exons, while themselves also directly subject to natural selection. The H2Eb(p) alleles form a distinct group, associated with their lack of the recombination hot spot located between exon 2 and exon 3. The collection is expected to prove useful in guiding functional and evolutionary studies. PMID- 17284223 TI - The role of the IDDM2 locus in the susceptibility of UK APS1 subjects to type 1 diabetes mellitus. AB - Autoimmune polyendocrinopathy syndrome type 1 (APS1) is characterized by autoimmune destruction of endocrine tissues and chronic mucocutaneous candidiasis. Type 1 diabetes (T1D) affects 12-25% of patients with APS1, and the prediction of whether this complication will affect an individual is not currently possible. However, alleles of a variable number tandem repeat (VNTR) 5' of the insulin gene are known to influence the development of T1D in the general, non-APS1 population. Therefore, we investigated the prevalence of these IDDM2 alleles in British Caucasian patients with APS1. The study employed genotyping of 33 patients with APS1 for the HphI polymorphism that is in tight linkage disequilibrium with the insulin gene VNTR alleles. Thirty-three patients with APS1 were studied, the mean age was 23.5 years and 24% have T1D. Six of eight (75%) APS1 patients with T1D were homozygous for the class I INS VNTR (susceptibility) allele, compared with eight of 25 (32%) of APS1 patients without T1D (P = 0.042). Our data suggest an association between the development of T1D and homozygosity for the T1D susceptibility class IINS VNTR allele in patients with APS1. PMID- 17284222 TI - A novel HLA-A2 variant, A*9203, identified by sequence-based typing. AB - HLA-A*9203, found in Taiwan using sequence-based typing method, was identical to HLA-A*0207 in exon 3 but differed in exon 2 by five nucleotide substitutions at positions 240-282 corresponding to three amino acid changes at codons 62, 66 and 70. Since this substitution motif is also seen in A*11 and A*03, it is likely that a gene conversion event from A*11 or A*03 to a A*0207 backbone may have been the process used in generating HLA-A*9203. PMID- 17284224 TI - HLA-DRB1*03 is a susceptibility gene in patients with Graves' disease with and without ophthalmopathy. AB - We sought an association between certain human leucocyte antigen (HLA) markers and Graves' disease (GD) with and without ophthalmopathy (OP). One hundred and thirty-one Turkish patients with GD (50 without OP, 81 with OP) and 250 local healthy controls were studied. HLA-DRB1 typing was performed by using polymerase chain reaction-sequence-specific primers (PCR-SSP) method. The frequencies of DRB1*03 was significantly increased in GD compared to controls (OR = 2.07; 95% CI = 1.24-3.44), whereas DRB1*13 (OR = 0.33; 95% CI = 0.18-0.61) and DRB1*07 (OR = 0.31; 95% CI = 0.13-0.70) were significantly increased in controls compared to patients. None of the three associations showed any specificity to the OP group. PMID- 17284225 TI - Genetic diversity of the IL-4, IL-4 receptor and IL-13 loci in mestizos in the general population and in patients with asthma from three subpopulations in Mexico. AB - Asthma is an inflammatory airway disease characterized by increased serum IgE levels, mucus hypersecretion and infiltration of inflammatory cells, and is a multifactorial disease that exhibits genetic heterogeneity. Polymorphisms in the interleukin-4 (C-590T), interleukin-4 receptor (ile50val and gln576arg), and interleukin-13 (arg130gln) genes have been described as susceptibility alleles for asthma. This study was designed to determine whether asthma susceptibility is influenced by genotypic and allelic distribution of the above polymorphisms in three Mexican subpopulations. Four hundred and thirty-seven subjects from three Mexican subpopulations were classified into two groups: general population and affected/unaffected and genotyped for the above polymorphisms. We compared the distributions of the loci in the groups. In addition, we undertook association analysis between these loci and asthma phenotype in each affected/unaffected group, and determined Nei's genetic distance between the three subpopulations. The allelic and genotypic distributions of the polymorphisms differed between the three subpopulations. There was no association between any of the polymorphisms and asthma phenotype. However, there was a differential distribution of haplogroups (P < 0.0001) between the affected and the unaffected groups from the subpopulations of Jalisco and Guerrero. The genetic distribution of the four polymorphisms in the subpopulations did not influence susceptibility to asthma. Furthermore, the difference in the prevalence of asthma in these subpopulations is not attributable to the genetic background for the four polymorphisms analysed. However, haplogroup analysis suggests that the interaction of the polymorphisms and other predisposing alleles leads to the expression of the clinical phenotype. PMID- 17284226 TI - Association of IL12RB1 polymorphisms with susceptibility to and severity of tuberculosis in Japanese: a gene-based association analysis of 21 candidate genes. AB - Tuberculosis (TB) is the second commonest cause of death from infectious disease after HIV/AIDS worldwide. Association studies have revealed that host genetic factors, such as human leukocyte antigen and solute carrier family 11 member A1 (NRAMP1), play roles in susceptibility to TB. To identify host genetic factors involved in the susceptibility to TB in Japanese, we performed a gene-based association analysis of 21 candidate genes on 87 TB patients and 265 controls using marker single nucleotide polymorphisms (SNPs). For the genes with two or more marker SNPs exhibiting significant allele association, we subsequently analysed the association between adjacent coding SNPs (cSNPs) and TB. Among a total of 118 marker SNPs, 3 of IL1B and 2 of IL12RB1 showed association with TB. Non-synomymous cSNPs were not identified in IL1B. Association studies on four non synomymous cSNPs of IL12RB1 (641A/G, 1094T/C, 1132C/G, 1573G/A) in linkage disequilibrium showed that three of them (641A/G, 1094T/C, 1132C/G) were significantly associated with the development of TB. Haplotype analysis on the four cSNPs demonstrated that frequency of ATGG haplotype was significantly lower in TB patients than in controls. When TB patients were divided into two subgroups according to the severity of lung disease, advanced subgroup showed a prominent association with 641A/G, 1094T/C and 1132C/G SNPs. These data suggested that genetic variants of IL12RB1, at least in part, confer genetic susceptibility to TB, and are associated with the progression of the disease, in Japanese. PMID- 17284227 TI - Analysis of CD28 and CTLA-4 gene polymorphisms in Turkish patients with Behcet's disease. AB - In this study we aimed to investigate IVS3 +17T/C single nucleotide polymorphism (SNP) of CD28 gene, +49A/G and -318C/T SNPs of CTLA-4 gene in patients with Behcet's disease (BD) and their potential association to the main clinical features of the disease. These polymorphisms were investigated in a Turkish population of 123 patients with BD and 179 healthy controls, by using PCR-RFLP technique. HLA-B*51 genotype was also studied in both groups by using PCR-SSP. The frequency of IVS3 +17TC genotype of the CD28 gene was significantly increased in BD patients compared to controls (43.6% vs. 31.2%, OR = 1.663, 95% CI = 1.033 2.679, P = 0.039). CTLA-4 +49GG genotype frequency was found to be significantly lower in patients with BD than those of healthy controls (4% vs. 10.6%, OR = 0.357, 95% CI = 0.130-0.983, P = 0.05). Genotype and allele frequencies of the CTLA-4-318C/T polymorphism between the BD and healthy control groups were not significantly different (12.2% vs. 10.6%, OR = 1.170, 95% CI = 0.570-2.402, P = 0.713). There were no associations between the studied polymorphisms and the main clinical features of BD. The frequencies of HLA-B*51 were 60.3% and 30.7% in BD and control groups, respectively (OR = 3.429, 95% CI = 2.115-5.559, P = 0.0001). Association between HLA-B*51 and each studied polymorphism did not reach to significant levels (OR = 0.479, 95% CI = 0.228-1.004, P = 0.064 for CD28 IVS3 +17TT genotype; OR = 2.180, 95% CI = 1.025-4.639, P = 0.061 for TC genotype; OR = 1.570, 95% CI = 0.870-2.836, P = 0.146 for C allele). These results may suggest that CD28 IVS3 +17TC genotype may be a risk factor for the development of BD, on the contrary CTLA-4 +49GG genotype may be protective in the studied Turkish population. PMID- 17284228 TI - IkappaBalpha promoter polymorphisms in patients with rheumatoid arthritis. AB - To investigate the role of inhibitor of kappaBalpha promoter polymorphisms in the pathogenesis of rheumatoid arthritis (RA), 140 patients with RA and 115 healthy controls were enrolled in this study. The IkappaBalpha promoter polymorphisms were determined using the polymerase chain reaction/restriction fragment length polymorphisms method. In comparison with IkappaBalpha-826 C/C, the genotype frequency of IkappaBalpha-826 C/T was significantly higher in the patients with RA than that of the controls (P = 0.009, OR = 2.0, 95% CI = 1.2-3.4). The allele frequency of IkappaBalpha-826 T was also significantly increased in patients with RA when compared with that of the controls (P = 0.027, OR = 1.6, 95% CI = 1.1 2.4). In comparison with IkappaBalpha-550 A/A, the genotype frequency of IkappaBalpha-550 A/T was significantly decreased in patients with RA when compared with that of the controls (P = 0.02, OR = 0.2, 95% CI = 0.06-0.8). The allele frequency of IkappaBalpha-550 A was significantly increased in patients with RA (P = 0.007, OR = 5.1, 95% = 1.4-18.2). This study also revealed that the IkappaBalpha-826 T -550 A -519 C haplotype was significantly increased in patients with RA in comparison to that of controls (P = 0.01, OR = 1.8, 95% CI = 1.1-2.8). The IkappaBalpha-826 T and -550 A alleles are associated with susceptibility to RA. Moreover, the IkappaBalpha-826 T -550 A -519 C haplotype is associated with susceptibility to RA in Taiwan. PMID- 17284229 TI - Molecular genetic analysis of porcine mannose-binding lectin genes, MBL1 and MBL2, and their association with complement activity. AB - Mannose-binding lectin (MBL) mediates activation of the complement system via the lectin pathway. Two forms of MBL, MBL-A and MBL-C, were characterized in rodents, rabbits, bovine and rhesus monkeys, whereas only one form was identified in humans, chimpanzees and chickens. The two forms are encoded by two distinct genes named MBL1 and MBL2, which have been identified in many species including the pig. In this report, we studied the two porcine genes MBL1 and MBL2. The porcine MBL genes had higher identities to bovine rather than primate and rodent sequences. Both genes were assigned to chromosome 14 by radiation hybrid panel and linkage mapping. Both MBL genes were highly expressed in liver. MBL1 was also found to be expressed in the lung, testis and brain, whereas low expression of MBL2 was detected in the testis and kidney. New single nucleotide polymorphisms of porcine MBL2 gene were found and genotyped in an experimental F2 pig population, together with a previously reported SNP of MBL1. MBL1 genotypes differed in C3c serum concentration, i.e. in vivo complement activity, at P < 0.1. Correspondingly, linkage analysis revealed a quantitative trait locus for C3c serum level close to the position of the MBL genes. The study thus promotes the porcine MBL genes as functional and positional candidate gene for complement activity. PMID- 17284233 TI - A holistic approach to child psychiatric nursing: a new interdisciplinary collaboration. PMID- 17284235 TI - A model for caregiving of adopted children after institutionalization. AB - TOPIC: Optimizing caregiving for newly adopted postinstitutionalized children. PURPOSE: To consider a template of care for postinstitutionalized children based on experiences that physiological measures suggest are expected by infants postbirth. SOURCES: Published literature and clinical experience. CONCLUSION: Based on an understanding of physiologically expected care postbirth, special care for postinstitutionalized adopted children might include: close physical contact via use of a sling and cosleeping; breastfeeding or nurturing through food; and responsive caregiving. In replicating earlier missed experiences, parents may assist emotional development in their child and promote attachment development. PMID- 17284234 TI - A support group intervention for children bereaved by parental suicide. AB - TOPIC: Bereavement is considered by many to be among the most stressful of life events, and it becomes particularly distressing when it concerns the suicide death of a parent. Such an event is especially traumatic for children. PURPOSE AND SOURCES: The purpose of this paper is to present a case for support group interventions designed specifically for child survivors of parental suicide. The authors provide a theoretical framework for supportive group interventions with these children and describe the structure of an 8-week bereavement support group for this special population of suicide survivors. CONCLUSIONS: A case is made for designing and implementing group interventions to meet the mental health needs of this important group of individuals. PMID- 17284236 TI - Attachment theory and reactive attachment disorder: theoretical perspectives and treatment implications. AB - TOPIC: Attachment theory and reactive attachment disorder (RAD). PURPOSE: To highlight current perspectives on attachment theory, RAD, and treatment implications using a case study of an 8-year-old patient with RAD. SOURCES: Selected multidisciplinary literature related to attachment theory and RAD. CONCLUSIONS: The literature provides a body of work that substantiates the importance of early attachment relationships to human development and highlights gaps in our knowledge related to treatment of children with RAD. The quality of early attachment relationships is correlated with future personality and brain development. Attachment disturbances are associated with psychopathology in childhood and adulthood. Although evidence for the effective treatment of children with attachment disorders is minimal and inconclusive, the two major perspectives, developmental psychology and neuropsychoanalysis, offer guidelines for practice. PMID- 17284237 TI - Pediatric bipolar disorder: evidence-based psychopharmacological treatments. AB - TOPIC: Pediatric bipolar disorder can cause severe disturbances in global functioning. Diagnosing pediatric bipolar disorder is challenging due to the range of symptom expression, developmental differences as compared to adults, presence of comorbid disorders, and developing diagnostic criteria. Treating this disorder can be equally challenging due to frequent symptom relapse and the dearth of research until recently on effective psychopharmacological interventions that guide clinical prescribing practices. PURPOSE: This paper will help child psychiatric nurses have a better understanding of the unique presentation of pediatric bipolar disorder to facilitate selection of appropriate medication treatment options, taking into account symptom presentation, presence of comorbid diagnosis, drug efficacy, adverse effects, and drug-drug interactions based on research findings. SOURCES: Literature specific to assessment and psychopharmacological treatment of pediatric bipolar disorder was reviewed. CONCLUSIONS: Screening of youth with mood spectrum problems for bipolar disorder should occur in every diagnostic assessment and should be ongoing due to range of mood symptoms and the cyclical and episodic nature of this disorder. Youth with bipolar disorder may manifest symptoms and course that differ from adults. Additionally, co-occuring disorders are common in this population, which can complicate medication selection. Psychopharmacological treatment with the use of specific mood stabilizers and/or atypical antipsychotic medications is warranted depending on symptom presentation; however, monotherapy with mood stabilizers has not demonstrated effectiveness in long-term remission of pediatric bipolar symptoms. Recent research indicates that a combined treatment with two mood stabilizers or a mood stabilizer and an antipsychotic holds promising results for pediatric bipolar I, for youth with acute manic symptoms plus psychosis, and for long-term remission of symptoms. PMID- 17284238 TI - Treatment of hyperactivity in children with pervasive developmental disorders. PMID- 17284242 TI - The use of recombinant adeno-associated virus for skeletal gene therapy. AB - OBJECTIVES: To provide a comprehensive literature review describing recent developments of the recombinant adeno-associated virus (rAAV) vector and exploring the therapeutic application of rAAV for bone defects, cartilage lesions and rheumatoid arthritis. DESIGN: Narrative review. RESULT: The review outlines the serotypes and genome of AAV, integration and life cycle of the rAAV vectors, the immune response and regulating system for AAV gene therapy. Furthermore, the advancements of rAAV gene therapy for bone growth together with cartilage repair are summarized. CONCLUSION: Recombinant adeno-associated virus vector is perceived to be one of the most promising vector systems for bone and cartilage gene therapy approaches and further investigations need to be carried out for craniofacial research. PMID- 17284243 TI - The acceptability of variations in smile arc and buccal corridor space. AB - OBJECTIVES: To evaluate the esthetic acceptability range of computer-generated variations in smile arc and buccal corridor. DESIGN: Web-based descriptive study using available subjects. SETTING AND SAMPLE POPULATION: The World Wide Web. Subjects for the main study included 115 lay and 131 orthodontist raters. EXPERIMENTAL VARIABLES: Buccal corridors and smile arcs, each presented for a female and a male image. Buccal corridors were presented as none, ideal and excessive. The smile arc was presented as flat, ideal and excessive. The nine male and female variations, as combinations of the above variables, were each presented twice to evaluate reliability. OUTCOME MEASURE: Acceptability of buccal corridors and smile arcs using the web-based instrument. An arbitrary super majority threshold of acceptability was set at 67% approval. RESULTS: Both laypersons and orthodontists showed good reliability (k >or= 0.70). There was a broad range of acceptability, but laypersons and orthodontists showed no significant differences on the two variables tested. While orthodontists and laypersons both found smiles with excessive buccal corridors to be significantly less acceptable than those with ideal or absent buccal corridors, they were still acceptable over 70% of the time. Flat smile arcs were only acceptable 50-60% of the time, while smiles with ideal and excessive smile arcs were significantly more acceptable 84-95% of the time. When examining buccal corridors and smile arcs together, excessive buccal corridors were significantly less acceptable than ideal or absent buccal corridors regardless of the smile arc. A flat smile arc significantly reduced the acceptability of any buccal corridor to below the threshold of acceptability. CONCLUSIONS: Laypersons and orthodontists have similar preferences when acceptability of buccal corridors and smile arcs are considered. Flat smile arcs are more detrimental to smile esthetics than variations in buccal corridors. Clinicians must realize that although attractiveness may be reduced by variations in buccal corridors and smile arcs, the result may still be acceptable to a majority of people. PMID- 17284244 TI - Tails of the unexpected: palatal medial edge epithelium is no more specialized than other embryonic epithelium. AB - OBJECTIVE: To determine whether palatal medial edge epithelium (MEE) is specialized in its ability to disappear compared with other embryonic, non palatal, epithelium. SUBJECTS: Embryonic tissues harvested from CD1 mice. METHODS: Organs were cultured in 2 ml of DMEM/F12 supplemented with 300 microg/ml L-glutamine and 1% penicillin/streptomycin. Organs were cultured under various conditions including opposing other organs and opposing an inert material for a period of 6 days. Tissues were then processed for histological examination. RESULTS: MEE of shelves opposing nothing persisted, whereas MEE of shelves contacting another shelf disappeared. When a tail was placed against a palatal shelf the MEE disappeared, as did the epithelium from the tail, resulting in fusion between the shelf and tail. Furthermore, when palatal shelves were placed against an inert material the MEE disappeared, suggesting pressure alone is a sufficient stimulus to initiate disappearance of the MEE, and that the interaction between the two palatal shelves is not a prerequisite for the disappearance of MEE. Moreover, when two embryonic tails were cultured in close apposition they fused, as did paired limbs. Non-palatal epithelia also disappeared after contact with inert materials. Epithelial disappearance began within 24 h of contact, but there was an age limit. CONCLUSION: These findings suggest that embryonic epithelium from non-specific sites around the body has the ability to disappear with mechanical contact resulting in fusion of tissues. MEE may not be as specialized as once thought. PMID- 17284245 TI - A cephalometric study on craniofacial morphology of Iranian children with beta thalassemia major. AB - OBJECTIVE: To study cephalometric and facial features of Iranian children with beta-thalassemia major. DESIGN: Lateral cephalometric radiographs of thalassemic patients and controls who were matched for age, sex and ethnic origin were analyzed and compared. SETTING AND SAMPLE POPULATION: A total of 30 thalassemic patients (18 male and 12 females) from Aliasghar Hospital, and 30 controls from the Orthodontic Department of Azad University. OUTCOME MEASURE: Size and shape differences in the craniofacial complex between thalassemic patients and controls. RESULTS: All thalassemic patients had a Class II skeletal base relationship with an average ANB angle of 8.75 degrees. There was no record of dramatic maxillary prognathism. However, the mandible of the thalassemic patients appeared to be smaller in size and more retruded in the face. A pronounced vertical growth direction was evident from angular and linear measurements. The dental deviations in thalassemic patients were mainly seen in the proclination and significant overeruption of incisors and increased overjet. Marked convex lower face and prominent upper and lower lips were evident from soft-tissue measurements. CONCLUSION: Anemia does not only produce overgrowth of the maxilla. It also produces a retardation of condylar and ramal growth of the mandible producing Class II skeletal pattern. PMID- 17284246 TI - Overexpression of caveolin-1 in a human melanoma cell line results in dispersion of ganglioside GD3 from lipid rafts and alteration of leading edges, leading to attenuation of malignant properties. AB - Caveolin-1 is a component of lipid rafts, and is considered to be a tumor suppressor molecule. However, the mechanisms by which caveolin-1 functions in cancer cells are not well understood. We generated caveolin-1 transfectant cells (Cav-1(+) cells) using a human melanoma cell line (SK-MEL-28) and investigated the effects of caveolin-1 overexpression on the GD3-mediated malignant properties of melanomas. Cav-1(+) cells had decreased cell growth and motility, and reduced phosphorylation levels of p130Cas and paxillin relative to controls. In floatation analysis, although GD3 was mainly localized in glycolipid-enriched microdomain (GEM)/rafts in control cells, it was dispersed from GEM/rafts in Cav 1(+) cells. Correspondingly, GD3 in Cav-1(+) cells stained uniformly throughout the membrane, whereas control cells showed partial staining of the membrane, probably at the leading edge. p130Cas and paxillin were stained in the leading edges and colocalized with GD3 in the control cells. In contrast, these molecules were diffusely stained and no definite leading edges were detected in Cav-1(+) cells. These results suggest that caveolin-1 regulates GD3-mediated malignant signals by altering GD3 distribution and leading edge formation. These results reveal one of the mechanisms by which caveolin-1 curtails the malignant properties of tumor cells. PMID- 17284247 TI - Tumor-specific antivascular effect of TZT-1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy. AB - TZT-1027 (soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect. PMID- 17284248 TI - Severity of gastritis determines glandular stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils. AB - Helicobacter pylori (H. pylori) infection causes chronic gastritis and is also related to gastric carcinoma. The present study focused on severity of H. pylori induced gastritis as a determinant of carcinogenesis. Seven-week-old male Mongolian gerbils were inoculated with H. pylori at experimental weeks 0, 12, or 18, then given N-methyl-N-nitorosourea (MNU) from weeks 20-40. At week 70, stomachs were then excised for histological examination 70, 58, or 52 weeks after H. pylori inoculation, respectively (Groups A, B, and C for long-, middle-, and short-term). The respective incidences of glandular stomach adenocarcinomas were 65.0% (13/20), 20.0% (2/10), and 23.0% (3/13) (P<0.05). Higher scores of infiltration of inflammatory cells, hyperplasia, intestinal metaplasia and mucosal bromodeoxyuridine (BrdU) labeling index in antrum and corpus mucosa, were seen in group A than B or C (P<0.05) and serum anti-H. pylori IgG titer and gastrin levels were also significantly higher, along with mRNA levels for mucosal interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The results demonstrated the term and severity of H. pylori infection to play important roles in gastric carcinogenesis, with essential involvement of chronic inflammation, especially increased rates of cell proliferation, in H. pylori-associated carcinogenesis. PMID- 17284249 TI - Sexual function and satisfaction in heterosexual couples when men are administered sildenafil citrate (Viagra) for erectile dysfunction: a multicentre, randomised, double-blind, placebo-controlled trial. AB - OBJECTIVE: To investigate the effect of improvement in erectile dysfunction (ED) on sexual function and satisfaction measures in heterosexual couples in which the woman reports that sexual intercourse is unsatisfactory at least half of the time. DESIGN: Multicentre, double-blind, placebo-controlled study. SETTING: Outpatient medical clinics. POPULATION: Hundred and eighty men with ED and their female partners in whom sexual intercourse was satisfactory about half the time or less (score of < or =3 on the Female Partner of ED Subject Questionnaire question 3 [FePEDS Q3]). METHODS: Men were randomised to flexible-dose sildenafil (25, 50, and 100 mg) or placebo as needed for 12 weeks. MAIN OUTCOME MEASURES: Primary: FePEDS Q3 ('Over the past four weeks, when you had sexual intercourse, how often was it satisfactory for you?') scored as 0 (no sexual activity) and 1 (almost never or never) to 5 (almost always or always). Secondary, partners: Sexual Function Questionnaire, Female Sexual Function Index (FSFI), and ED Inventory of Treatment Satisfaction (EDITS) partner version (EDITS-Partner). Secondary, men: International Index of Erectile Function (IIEF), General Efficacy Questions, event log data, Self-Esteem And Relationship questionnaire, and EDITS. Secondary, partners and men: Dyadic Adjustment Scale. RESULTS: The intention-to treat population included 85 sildenafil recipients (mean age 59 +/- 12 years) and 91 placebo recipients (mean age 57 +/- 11 years). Most partners (aged 20-79 years; mean, 54 years) were postmenopausal. Sildenafil compared with placebo couples had greater improvement in the primary outcome (FePEDS Q3 [P < 0.0001]) and in sexual function, intercourse success rates, and secondary sexual satisfaction measures (FSFI satisfaction domain [P < 0.0001] and IIEF satisfaction domains [P < 0.001]) and had higher treatment satisfaction (EDITS and EDITS-Partner; P < 0.0001). Several predictors of improvement were identified, and improvement in one member of the couple correlated positively with improvement in the other member. CONCLUSIONS: The interdependence of sexual function and sexual satisfaction measures between members of couples consisting of men with ED and sexually healthy women reporting infrequent satisfactory sexual intercourse underscores the importance of including partners in ED treatment discussions. PMID- 17284251 TI - MEK-ERK is involved in SUMO-1 foci formation on apoptosis. AB - Small ubiquitin-related modifier (SUMO) modification appears to regulate the activity, intracellular localization, and stability of the targeted proteins. To explore the relationship among sumoylation, antitumor reagent, and apoptosis, we treated green fluorescence protein (GFP)-SUMO-1-overexpressed K562 cells (K562/GFP-SUMO-1) with mitoxantrone (MIT) as an antitumor reagent. By the treatment with MIT, GFP-SUMO-1 formed foci in nuclei. While by the treatment with a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), GFP-SUMO-1 located homogeneously in nuclei. When K562/GFP-SUMO-1 cells were treated with TPA plus MIT, GFP-SUMO-1 foci became larger and apoptosis was induced more than with MIT alone. The apoptosis induced by TPA plus MIT was prevented by blockage of GFP SUMO-1 foci by small interfering RNA (siRNA) against SUMO-1. The formation of GFP SUMO-1 foci was reduced by a MEK inhibitor U0126 or a nuclear export inhibitor leptomycin B, and endogenous SUMO-1 foci were reduced in K562 cells expressing the dominant-negative MEK1 mutant. These results suggest that the formation of SUMO-1 foci is regulated by the MEK-ERK pathway and may induce apoptosis. PMID- 17284252 TI - Prediction of in vitro response to interferon-alpha in renal cell carcinoma cell lines. AB - We analyzed the correlation between interferon-alpha (IFNalpha) response and gene expression profiles to predict IFNalpha sensitivity and identified key molecules regulating the IFNalpha response in renal cell carcinoma (RCC) cell lines. To classify eight RCC cell lines of the SKRC series into three subgroups according to IFNalpha sensitivity, that is, sensitive, resistant and intermediate group, responses to IFNalpha (300-3000 IU/mL) were quantified by WST-1 assay. Microarray, followed by supervised hierarchical clustering analysis, was applied to selected genes according to IFNalpha sensitivity. In order to find alteration of expression profiles induced by IFNalpha, sequential microarray analyses were performed at 3, 6, and 12 h after IFNalpha treatment of RCC cell lines and mRNA expression level was confirmed using quantitative real time polymerase chain reaction. According to the sequential microarray analysis between IFNalpha sensitive and -resistant line, seven genes were selected as candidates for IFNalpha-sensitivity-related genes in RCC cell lines. Among these seven genes, we further developed a model to predict tumor inhibition with four genes, that is, adipose differentiation-related protein, microphthalmia associated transcription factor, mitochondrial tumor suppressor 1, and troponin T1 using multiple linear regression analysis (coefficient=0.948, P=0.0291) and validated the model using other RCC cell lines including six primary cultured RCC cells. The expression levels of the combined selected genes may provide predictive information on the IFNalpha response in RCC. Furthermore, the IFNalpha response to RCC might be modulated by regulation of the expression level of these molecules. PMID- 17284253 TI - Translocation of heparanase into nucleus results in cell differentiation. AB - We recently reported that heparanase, one of the extracellular matrix-degrading enzymes, which plays a critical role in cancer progression, is located not only in the cytoplasm but also in the nucleus. Here we identified nuclear translocation of heparanase as a key step in cell differentiation. We applied an in vitro differentiation model of HL-60 cells with 12-0-tetradecanoylphorbol-13 acetate (TPA), in which nuclear translocation of heparanase was observed using immunohistochemical analysis. In this system, nuclear translocation of heparanase was abolished by inhibitors of heat shock protein 90 (HSP90), suggesting the involvement of HSP90 in translocation of heparanase. We further confirmed that overexpression of active form of heparanase induced differentiation of HL-60 cells, although the catalytic negative form of heparanase did not. Therefore we speculate that nuclear translocation of enzymatically active heparanase may be involved in cellular differentiation. Our results suggest that a novel function of heparanase upon cell differentiation would raise a potential new strategy for cancer therapy of promyeloid leukemia and other types of cancer. PMID- 17284250 TI - Succession in the intestinal microbiota of preadolescent turkeys. AB - In the present study, automated ribosomal intergenic spacer analysis (ARISA), library sequence analysis, real-time PCR detection of Bacteroides uniformis and Campylobacter coli and dot-blot hybridizations of Clostridiaceae were used to identify trends in microbial colonization of the ceca of male turkeys. Two separate trials were performed with six and five birds, respectively. ARISA community profiles identified a period of community transition at week 12 of age in both trials. A significant increase of Ca. coli was also detected at week 12 in one trial, suggesting a possible correlation between microbiota destabilization and pathogen prevalence. Libraries of ribosomal small subunit 16S genes representing weeks 9, 11, 12 and 14 of both trials were sequenced. Whereas fingerprint and sequence analyses indicated significant differences in the species composition between the two trials, in general sequence library and dot blot analyses indicated that Clostridia-like species decreased in prevalence over time. While B. uniformis prevalence in the two trials rose from 7% and 0% of the library clones at week 9 to 84% and 79% at week 11, real-time PCR did not support these results, with only approximately twofold and sixfold increases in internal transcribed spacer copy numbers observed. PMID- 17284254 TI - Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells. AB - Dietary phytochemicals, including nobiletin and auraptene, have been shown to exert inhibiting effects in several chemically induced carcinogenesis models. We here investigated the influence of nobiletin and auraptene on prostate carcinogenesis using transgenic rats developing adenocarcinoma of the prostate (TRAP) bearing the SV40 T antigen transgene under control of the probasin promoter and human prostate cancer cells. Starting at 5 weeks of age, male TRAP rats received powder diet containing 500 p.p.m. nobiletin or auraptene, or the basal diet for 15 weeks and then were sacrificed for analysis of serum testosterone levels and histological changes. The body and relative prostate weights and serum testosterone levels did not differ among the groups. Since all animals developed prostate carcinomas, these were semiquantitatively measured and expressed as relative areas of prostate epithelial cells. Nobiletin caused significant reduction in the ventral (P<0.01), lateral (P<0.001) and dorsal (P<0.05) prostate lobes, while decreasing high grade lesions (P<0.05) in the ventral and lateral lobes. Feeding of auraptene also effectively reduced the epithelial component (P<0.05) and high grade lesions (P<0.05), in the lateral prostate. A further experiment demonstrated that growth of androgen sensitive LNCaP and androgen insensitive DU145 and PC3 human prostate cancer cells, was suppressed by both nobiletin and to a lesser extent auraptene in a dose-dependent manner, with significant increase in apoptosis. In conclusion, these compounds, particularly nobiletin, may be valuable for prostate cancer prevention. PMID- 17284256 TI - 'On environmental carcinogens: from an era of risk evaluation to an era of risk management' Tokyo, Japan, 29 july 2006. PMID- 17284255 TI - Immunohistochemical diagnosis of the cagA-gene genotype of Helicobacter pylori with anti-East Asian CagA-specific antibody. AB - Cytotoxin-associated antigen A (CagA) protein produced by Helicobacter pylori is proposed to be associated with the pathogenesis of gastric cancer as well as gastritis and gastroduodenal ulcer. It has been reported that the CagA of H. pylori widespread in East Asian countries, where the mortality rate due to gastric cancer is high, is structurally different from that in Western countries, where the gastric cancer mortality rate is relatively low. In this study, we generated an antibody, East Asian CagA-specific antibody (alpha-EAS Ab), which is specifically immunoreactive with East Asian CagA but not with Western CagA. The CagA was immunohistochemically detected at the surface of the gastric mucosa. Interestingly, positive immunoreactivity was also detected in the nucleus and cytoplasm of the infected gastric epithelium, suggesting that CagA may play some pathogenic role in both the nucleus and cytoplasm. Immunohistochemistry of 47 gastric biopsy specimens detected East Asian CagA-positive H. pylori in 43 cases. In 46 of the 47 cases examined, the data obtained by immunohistochemistry were completely consistent with those obtained by sequencing of the cagA gene of the isolated strain, suggesting that our immunohistochemical method is reliable and useful for diagnosis of the cagA genotype. PMID- 17284258 TI - Optimizing catheter navigation for AF ablation: do not just follow the map! PMID- 17284257 TI - Differential expression of the human alpha-enolase gene in oral epithelium and squamous cell carcinoma. AB - alpha-Enolase and c-myc promoter binding protein 1 are encoded by a single gene, ENO1, and are synthesized from the same transcript through alternative use of translational start sites. We have investigated the localization of ENO1 gene transcripts detected as proteins with an immunohistochemical method and also as mRNA with an in situ hybridization method on tissue sections of oral epithelium and oral squamous cell carcinoma, and demonstrated the differential distribution of the gene transcripts in normal oral epithelium and oral squamous cell carcinoma in humans. Expression of the ENO1 transcript was detectable in the region from the basal cell layers to the lower granular cell layers. Three patterns of ENO1 localization were observed with immunostaining in the epithelia: cytoplasm, nuclei, and both nuclei and cytoplasm. These patterns were observed randomly within the same specimen. In contrast to normal oral epithelium, ENO1 protein was not detectable in the nuclei of carcinoma cells. Our results indicate that differential subcellular localization of ENO1 products may be closely related to carcinogenesis of the oral epithelium. PMID- 17284259 TI - Dynamic effects of exercise and different escape rhythms on the supernormal period of an accessory pathway. AB - Spontaneous conduction during the supernormal period (SNP) of accessory pathways (AP) is rare and observed only during atrio-ventricular block (AVB). The effect of exercise and different escape rhythms on the SNP is unknown. We evaluated these factors on the SNP of a para-Hisian AP after a failed ablation complicated by AVB. The SNP onset and duration were later and longer during paced versus junctional rhythm. Exercise caused linear shortening of the SNP that was directly related to junctional cycle length. The SNP is a dynamic window shifting in parallel with AP refractoriness and affected by exercise and type of escape rhythm. PMID- 17284260 TI - Occam's razor and the unraveling of atrial fibrillation. AB - The search for a mechanism to explain atrial fibrillation (AF) has lasted for over a century and continues. Significant progress in understanding this arrhythmia accelerated with the era of operative treatment of this arrhythmia and intensified with the advent of catheter ablation. Through considerable trial and some error, effective "curative" therapies have evolved for paroxysmal AF and are evolving for persistent AF. It is becoming clear that no single mechanism suffices to explain AF in all its forms and multiple mechanisms are playing a role in the most complicated cases. PMID- 17284261 TI - Left atrial "mitral isthmus" block after radiofrequency ablation? PMID- 17284262 TI - Computed tomography-fluoroscopy image integration-guided catheter ablation of atrial fibrillation. AB - INTRODUCTION: This study examines the feasibility of atrial fibrillation (AF) ablation using registered three-dimensional computed tomography (CT) images of the left atrium with fluoroscopy. METHODS AND RESULTS: A total of 50 consecutive patients with symptomatic AF refractory to medical therapy (32 paroxysmal, 18 persistent, age 55 +/- 10 years) were randomized to undergo a catheter-based AF ablation procedure with or without the CT-fluoroscopy guidance system. All patients underwent preprocedural contrast-enhanced CT imaging and segmentation of the left atrium. For the CT-fluoroscopy group, circumferential lesions encompassing the pulmonary vein (PV) antrum and linear lesions along the roof of the left atrium between the superior PVs and the mitral isthmus were created on the CT image, which was registered with real-time fluoroscopy. The registered images were then used to navigate the ablation catheters to the sites of planned ablation. After the ablation sites were completed, any remaining PV potentials were isolated with electrophysiological guidance. In the control patients, the same technique was performed without using the CT-fluoro guidance system. CT scans were accurately registered to fluoroscopic images with minimal manual correction. Operators could navigate catheters on the registered images to preplanned, extraostial sites for ablation. CT-fluoroscopy guidance decreased procedure duration and fluoro times (P < 0.05). At a mean follow-up of 9 +/- 2 months, 21 patients (84%) in the CT-fluoro guidance group and 16 patients (64%) in the control group have had no recurrence of AF. CONCLUSION: CT-fluoroscopic guided left atrial ablation is feasible and allows appropriate catheter manipulation in the left atrium. PMID- 17284263 TI - Sustained benefit of cardiac resynchronization therapy. AB - INTRODUCTION: Most data on cardiac resynchronization therapy (CRT) are from trials with highly selected patients, with limited long-term echocardiographic data. This study was performed to evaluate long-term echocardiographic remodeling after CRT in daily practice. METHODS AND RESULTS: A biventricular pacemaker was implanted in 130 patients with advanced heart failure who met the general accepted criteria for CRT or in heart failure patients with a conventional pacemaker indication. Two years echocardiographic follow-up was available. Mean age (73 years) was higher than in the randomized trials. Forty-one patients (32%) died during the 2 year follow-up period. Mortality was higher in males, in patients with increased NT-proBNP, renal dysfunction, or left atrial dilatation before implantation. Echocardiographic response (LVEF improvement of 5% or more) was documented in 69, 88, and 91% of the survivors, after 3 months, 1 year, and 2 years, respectively. Echocardiographic response after 3 months was associated with a significantly higher long-term survival (P = 0.04). Mean LVEF was 22% at baseline compared to 31.8, 38.3, and 39.7% after 3 months, 1 year, and 2 years, respectively (P < 0.01). Reverse remodeling (a reduction of LV end systolic volume of more than 10%) was observed in 70.7, 81.0, and 91.7% of the survivors after 3 months, 1 year, and 2 years, respectively. Long-term LV improvement was more pronounced in patients with nonischemic cardiomyopathy. CONCLUSION: LV reverse remodeling and beneficial echocardiographic changes were sustained during 2 years follow-up. A 5% or more increase in LVEF after 3 months was associated with a better long-term survival. PMID- 17284264 TI - Nonlinear indices of heart rate variability in chronic heart failure patients: redundancy and comparative clinical value. AB - AIMS: We aimed to assess the mutual interrelationships and to compare the prognostic value of a comprehensive set of nonlinear indices of heart rate variability (HRV) in a population of chronic heart failure (CHF) patients. METHODS AND RESULTS: Twenty nonlinear HRV indices, representative of symbolic dynamics, entropy, fractality-multifractality, predictability, empirical mode decomposition, and Poincare plot families, were computed from 24-hour Holter recordings in 200 stable CHF patients in sinus rhythm (median age [interquartile range]: 54 [47-58] years, LVEF: 23 [19-28]%, NYHA class II-III: 88%). End point for survival analysis (Cox model) was cardiac death or urgent transplantation. Homogeneous variables were grouped by cluster analysis, and in each cluster redundant variables were discarded. A prognostic model including only known clinical and functional risk factors was built and the ability of each selected HRV variable to add prognostic information to this model assessed. Bootstrap resampling was used to test the models stability. Four nonlinear variables showed a correlation >0.90 with classical linear ones and were discarded. Correlations >0.80 were found between several nonlinear variables. Twelve clusters were obtained and from each cluster a candidate predictor was selected. Only two variables (from empirical mode decomposition and symbolic dynamics families) added prognostic information to the clinical model. CONCLUSION: This exploratory study provides evidence that, despite some redundancies in the informative content of nonlinear indices and strong differences in their prognostic power, quantification of nonlinear properties of HRV provides independent information in risk stratification of CHF patients. PMID- 17284266 TI - Effect of light curing type on cytotoxicity of dentine-bonding agents. AB - AIM: To compare the cytotoxic effects of dentine-bonding agents (DBAs) polymerized with two different curing units at 24 h and 72 h on L-929 cells. METHODOLOGY: Disc-shaped test samples of light-activated DBAs were prepared according to manufacturers' instructions and cured with either conventional quartz tungsten halogen or light-emitting diode light curing units (LCUs). After curing, the samples were transferred into a culture medium for 24 h. Eluates were obtained and pipetted onto L-929 mouse fibroblast cultures (3 x 10(4) cells per well), incubated for evaluation after 24 and 72 h. After both incubation periods, measurements were performed by an dimethylthiazol diphenyltetrazolium assay. The degree of cytotoxicity for each sample was determined according to the reference value represented by the cells with a control (culture without sample). Statistical significance was determined by a three-way analysis of variance followed by the Mann-Whitney U-test. RESULTS: No significant three-factor interaction occurred amongst LCUs, DBAs and time factors (P = 0.955). LCUs and DBAs had a significant two-factor interaction (P < 0.001). In general, the test materials cured with the light-emitting diode LCU demonstrated higher cell survival rates when compared with the those cured with the quartz tungsten halogen. CONCLUSIONS: Differential toxic effects of the DBAs cured with the quartz tungsten halogen or the light-emitting diode on the fibroblast cells may prove to be very important when suitable DBAs or LCUs are used for operative restorations. PMID- 17284265 TI - Intracardiac echo-guided image integration: optimizing strategies for registration. AB - INTRODUCTION: Image integration is being used in ablation procedures. However, the success of this approach is dependent on the accuracy of the image integration process. This study aims to evaluate the in vivo accuracy and reliability of the integrated image. METHODS AND RESULTS: One hundred twenty-four patients undergoing radiofrequency (RF) ablation catheter ablation for atrial fibrillation (AF) were recruited for this study from three different centers. Cardiac computerized tomography (CT) was performed in all patients and a 3D image of the left atrium (LA) and pulmonary veins (PVs) was extracted for registration after segmentation using a software program (CartoMerge, Biosense Webster, Inc.). Different landmarks were selected for registration and compared. Surface registration was then done and the impact on integration and the landmarks was evaluated. The best landmark registration was achieved when the posterior points on the pulmonary veins were selected (5.6 +/- 3.2). Landmarks taken on the anterior wall, left atrial appendage (LAA) or the coronary sinus (CS) resulted in a larger registration error (9.1 +/- 2.5). The mean error for surface registration was 2.17 +/- 1.65. However, surface registration resulted in shifting of the initially registered landmark points leading to a larger error (from 5.6 +/- 3.2 to 9.2 +/- 2.1; 95% CI 4.2-3.05). CONCLUSION: Posterior wall landmarks at the PV-LA junction are the most accurate landmarks for image integration in respect to the target ablation area. The concurrent use of the present surface registration algorithm may result in shifting of the initial landmarks with loss of their initial correlation with the area of interest. PMID- 17284267 TI - Risk factors for developing apical periodontitis in a general population. AB - AIM: To identify and describe individual and tooth-specific factors associated with the incidence or the persistence of apical periodontitis (AP) in a general population. METHODOLOGY: In 1997, 616 randomly selected individuals had a full mouth radiographic survey. In 2003, 77% of the participants returned for a new full-mouth radiographic examination. All teeth were assessed individually and data recorded for caries, marginal bone level, and tooth restorations. Multiple logistic regression analyses were performed to identify predictors of AP in the individual. Conditional logistic regression analyses were used to identify risk factors for development of AP in a tooth. Independent variables included a number of individual and tooth-specific variables. RESULTS: Root fillings, coronal restorations, primary carious lesions, and reduced marginal bone level were associated with the incidence of AP in the individual. In teeth, the quality and presence of a coronal restoration was associated with the incidence of AP, and presence of a root filling also increased the risk of developing AP. Furthermore, an increased risk of developing AP was seen in relation to primary carious lesions, reduced marginal bone level, and molar teeth. The quality of the root filling was not associated with the incidence of AP, but the results suggest an association between the quality of the root filling and the healing of AP. CONCLUSIONS: Results from the present study demonstrate that it is important to provide high quality dental restorations to minimize the risk of pulpal infection. The clinical focus, in relation to the incidence of AP, should be on improving the quality of the coronal restoration. The quality of a root filling was not associated with the incidence of AP, but may be of importance in relation to healing of AP. PMID- 17284268 TI - Contemporary treatment of class II dens invaginatus. AB - AIM: To present the nonsurgical management of a tooth with class II dens invaginatus with an open apex utilizing contemporary techniques. SUMMARY: Root canal treatment of teeth with complex root canal anatomy such as dens invaginatus can be problematic because infected pulpal tissues may remain in inaccessible areas of the canal system. The cleaning and debridement of such root canal systems are therefore challenging and may sometimes be considered impossible. An immature apical root-end development is another challenge in root canal treatment especially in controlling the apical extent of the filling material and achieving an apical seal. When difficulties in cleaning and filling combine, management options may include surgical intervention or extraction. This article reports the nonsurgical endodontic treatment of a case of an open apex and dens invaginatus utilizing the operating microscope, endodontic ultrasonic instruments and mineral trioxide aggregate. KEY LEARNING POINT: Teeth with class II dens evaginatus and an open apex may be managed successfully with contemporary nonsurgical materials and techniques. PMID- 17284269 TI - Phase transformation behaviour and bending properties of hybrid nickel-titanium rotary endodontic instruments. AB - AIM: To investigate the bending properties of hybrid rotary nickel-titanium endodontic instruments in relation to their transformation behaviour. METHODOLOGY: Four types of nickel-titanium rotary endodontic instruments with different cross-sectional shapes (triangular-based and rectangular-based) and different heat treatment conditions (super-elastic type and hybrid type with shape memory effect) were selected to investigate bending properties and phase transformation behaviour. Bending load of the instruments was measured in a cantilever-bending test at 37 degrees C with the maximum deflection of 3.0 mm. A commercial rotary instrument, ProFile (PF; Dentsply Maillefer, Ballaigues, Switzerland) was used as a reference for the bending test. Phase transformation temperatures were calculated from the diagrams obtained from differential scanning calorimetry. Data were analysed by anova and Scheffe's test. RESULTS: The bending load values of the hybrid type that had undergone additional heat treatment at the tip were significantly lower (P < 0.05) than those of the super elastic type with no additional heat treatment. The bending load values of rectangular-based cross-sectional shaped instruments were significantly lower (P < 0.05) than those of triangular-based cross-sectional shaped instruments. Phase transformation temperatures (M(s) and A(f) points) of the hybrid type were significantly higher (P < 0.05) than the super-elastic type. The M(f) and A(s) points of the tip part were significantly higher (P < 0.05) than those of the whole part of the hybrid instrument. CONCLUSIONS: Additional heat treatment of hybrid nickel-titanium instruments may be effective in increasing the flexibility of nickel-titanium rotary instruments. PMID- 17284270 TI - Morphometric study of the apical anatomy of C-shaped root canal systems in mandibular second molars. AB - AIM: To investigate the apical anatomy of C-shaped canal systems in mandibular second molars by micro-computerized tomography (microCT) and stereomicroscopy. METHODOLOGY: Forty-four permanent mandibular second molars with a C-shaped root canal systems from a native Chinese population were scanned at 100 microm intervals by microCT at a resolution of 30 x 30 microm. The apical 5 mm of each tooth was reconstructed three-dimensionally for visualization and classification of the canal configuration using Vertucci's criteria. The main and auxiliary (accessory) foramina were examined under a stereomicroscope. RESULTS: Type IV and VIII canal configurations were most often found in the apical 5 mm of these canal systems. The prevalence of accessory canals, lateral canals, inter-canal communications and apical delta were 41%, 25%, 27% and 11%, respectively. Approximately 80% of C-shaped canals had 1-3 apical foramina; the prevalence of accessory foramina was about 48%. The mean distance between the main foramen and the anatomic root apex was 0.84 mm, and that between the accessory foramen and the apex was 1.61 mm. The mean (shortest and longest) diameters of major and accessory foramina were 0.19 - 0.32 mm and 0.07 - 0.10 mm, with a mean form factor of 0.73 and 0.82, respectively. CONCLUSION: The apical anatomy of C-shaped root canal systems in mandibular second molars is extremely complex with many anatomical variations. PMID- 17284271 TI - Increasing vigilance on the medical/surgical floor to improve patient safety. AB - AIM: This paper reports a study designed to assess an automated non-invasive, patient vigilance system, the (L)G(1TM) system, for determining heart rate and respiration rate. The study uses collected data to optimize the (L)G(1TM)'s alert management scheme for medical/surgical wards. BACKGROUND: Thousands of patients die unnecessarily each year because of compromised patient safety in hospitals. Economic pressures to reduce hospitalization costs, exacerbated by increasing nursing shortages, have created a need for new approaches to patient vigilance. Advanced technologies may help nurses to provide high-quality care while controlling costs and improving patient safety. METHODS: Heart and respiration waveforms from 287 patients were captured by sensor arrays embedded in the mattress coverlets of their beds. No real-time monitoring was performed. Raw data were processed by proprietary algorithms and compared with data captured by a standard reference device. Alert performance was verified by hand-scoring the signal data and matching it against clinical events observed through a systematic review of each patient's medical record. The data were collected between June 2004 and February 2005. RESULTS: Experimental algorithms for heart rate had an accuracy of -1.47 (sd 1.90) and a precision of 4.60 (sd 2.46). Respiration rate algorithms showed an accuracy of -0.94 (sd 1.26) and a precision of 4.02 (sd 1.17). Algorithms identified 178 true-positive physiological alerts on 15 patients. None of the events was deemed clinically significant at chart review. The combined false-positive alert rate for the algorithms was 0.007 events per hour. CONCLUSION: This study demonstrates the accuracy and precision of the signal processing algorithms in the (L)G(1TM) system. Future work will focus on assessing the system's impact on patient outcomes and its integration into the nursing workflow. PMID- 17284272 TI - Postoperative recovery: a concept analysis. AB - AIM: This paper presents a concept analysis of the phenomenon of postoperative recovery. BACKGROUND: Each year, millions of patients throughout the world undergo surgical procedures. Although postoperative recovery is commonly used as an outcome of surgery, it is difficult to identify a standard definition. METHOD: Walker and Avant's concept analysis approach was used. Literature retrieved from MEDLINE and CINAHL databases for English language papers published from 1982 to 2005 was used for the analysis. FINDINGS: The theoretical definition developed points out that postoperative recovery is an energy-requiring process of returning to normality and wholeness. It is defined by comparative standards, achieved by regaining control over physical, psychological, social and habitual functions, and results in a return to preoperative level of independence/dependency in activities of daily living and optimum level of psychological well-being. CONCLUSION: The concept of postoperative recovery lacks clarity, both in its meaning in relation to postoperative recovery to healthcare professionals in their care for surgical patients, and in the understanding of what researchers in this area really intend to investigate. The theoretical definition we have developed may be useful but needs to be further explored. PMID- 17284273 TI - Nurses' perception of shift handovers in Europe: results from the European Nurses' Early Exit Study. AB - AIM: This paper reports a study exploring nurses' perceptions of the shift handover and the possible reasons for reported dissatisfaction in 10 European countries. BACKGROUND: The nursing handover fulfils a number of purposes and has important consequences for the continuity of patient care and nurses' satisfaction with the quality of care they are able to provide. However, the performance and function of shift handovers in health care is a widely neglected topic in practice and research. METHOD: The Nurses' Early Exit Study (http://www.next-study.net) investigates the working conditions of nurses and variables influencing nursing retention. The data for this analysis were collected between 2002 and 2003 by self-report questionnaires in 10 European countries. FINDINGS: The percentage of nurses dissatisfied with shift handovers ranged from 22% in England to 61% in France. In most countries the main reason for dissatisfaction with shift handovers was 'too many disturbances', followed by 'lack of time'. Most countries showed similar associations of dissatisfaction with qualification level and occupational seniority, but not with position and type of shift. 'Poor quality of leadership' and 'poor support from colleagues', were strongly associated with dissatisfaction. CONCLUSIONS: In several (but not all) European countries, shift handovers may be a frequent cause for nurses' irritation. The underlying causes appear to be of an organizational nature. The findings have implications for solutions. Further debate and research should clarify the different purposes of shift handovers and relate them to handover style and to the quality of patient care. PMID- 17284274 TI - Keeping nurses working: development and psychometric testing of the Nurse-Work Instability Scale (Nurse-WIS). AB - AIM: This paper reports a study to develop and test the psychometric properties of the Nurse-Work Instability Scale (Nurse-WIS). BACKGROUND: Work Instability describes the extent of any mismatch among functional (in)capacity, work demands and its potential impact on efficiency/productivity at work. Recruitment, retention and migration of nurses are global issues influenced by many factors. It is well documented that musculoskeletal pain and subsequent disability account for a high proportion of sickness absence and premature retirement in the nursing workforce. The challenge to clinicians is to identify such problems early so that appropriate interventions can be targeted to facilitate job retention. METHOD: Analyses of 48 qualitative interview transcripts conducted with nursing staff during 2003 were used to generate potential items for the Nurse-WIS. Analysis of the psychometric properties of the scale derived from these items was undertaken by using the Rasch model and data generated in postal surveys in 2004. The scale was validated against a gold standard of expert vocational assessment by occupational health physiotherapists/ergonomists. FINDINGS: The resulting self administered questionnaire consisting of 30 items not only measures the risk of job loss relating to musculoskeletal symptoms, but also captures relevant psychosocial issues. The scaling properties of this questionnaire meet the rigorous psychometric requirements of the Rasch model. CONCLUSIONS: The Nurse-WIS is a psychometrically sound method for the early identification of nursing staff experiencing difficulties at work. It offers the prospect of positive proactive management to prevent or minimize sickness absence and potentially prevent loss of nursing staff from the workforce through long-term sickness absence and early retirement. PMID- 17284275 TI - Impact of cardiac disease on couples' relationships. AB - AIM: This paper reports a study to describe meanings that couples mutually assign to, and practices they develop, after the onset of cardiac disease and to understand the impact of the illness on the couples' relationships in everyday life. BACKGROUND: Patients as well as partners are affected by the onset of cardiovascular disease. Social support within intimate relationships has been shown to be important for patient survival and well-being, and couples' coping strategies are pivotal for well-being and adjustment to the chronic condition in both patients with cardiovascular disease and their partners. METHOD: Twenty-four couples participated in this phenomenological study. Data were collected during 2003. Participants were interviewed after having been hospitalized due to an acute event and having participated in a rehabilitation programme. Three in-depth interviews were obtained for each dyad: one couple interview and two individual interviews with each partner of the dyad. Paradigm cases were sought and thematic analyses conducted. FINDINGS: All couples experienced a 'brush with death' at the onset of heart disease, which called for changes in lifestyle. Three distinct patterns of dealing with the illness emerged. The first revealed that some couples assess the illness as a positive, transformative experience in their lives, bringing them closer together. The second showed that a proportion of couples experience the illness as a threat which imposes fear on both partners. The challenges are faced as mutual tasks and new routines are developed. The third pattern revealed couples who experience a missed opportunity to change. These couples are disenchanted about each other but return to life as usual. CONCLUSIONS: Nurses can use the information gained from this study to support couples in their attempts to come to terms with the illness, and can enhance their supportive role in rehabilitation efforts. PMID- 17284276 TI - Pressure ulcers and their treatment and effects on quality of life: hospital inpatient perspectives. AB - AIM: This paper reports a study exploring patients' perceptions and experiences of the impact of a pressure ulcer and its treatment on their health and quality of life. BACKGROUND: Pressure ulcers are a significant health problem, and their prevention and management in primary and secondary care is high on the clinical and policy agenda. However, patients' perspectives and experiences of the impact of pressure ulcers on health and quality of life is not understood. METHOD: Qualitative semi-structured interviews were carried out from 2002 to 2004 with a purposive sample of 23 hospital inpatients (five men, 18 women: aged 33-92 years) with a pressure ulcer (graded 2-5) at various anatomical sites and with varied reasons for hospital admission. Data were analysed thematically. FINDINGS: The majority of participants (91%; n = 21) indicated that the pressure ulcer and its treatment affected their lives emotionally, mentally, physically and socially. They presented their perspectives on the causes of their pressure ulcer and descriptions of pain (experienced by 91%), appearance, smell and fluid leakage. Patients described amounts and quality of care they received, including levels of comfort of dressings and pressure relieving equipment and the timing of interventions. They were largely dependent on others to treat, manage and care for their ulcer, but indicated that the pain, discomfort and distress of pressure ulcers was not acknowledged by nursing staff. The pressure ulcers could be pivotal in preventing full recovery, were perceived to increase hospital stays and resulted in ongoing treatments. CONCLUSION: Healthcare professionals can learn from these patients' experiences about the management of dressings, providing information (in particular about realistic time expectations for healing), providing preventative interventions and understanding the importance of comfort and positioning for patients. The study highlights the complexities of evaluating the impact of pressure ulceration. PMID- 17284277 TI - Predictors of treatment adherence in young children with type 1 diabetes. AB - AIM: This paper reports a study to investigate whether diabetes-specific, demographic and psychosocial variables predict adherence in young children with type 1 diabetes. BACKGROUND: Paediatric diabetes rates are increasing worldwide; however, young children are neglected in treatment adherence research, despite the importance of adherence for health. Greater understanding of adherence in this group could enhance nurses' ability to provide care tailored to families' needs. METHOD: A cross-sectional study was carried out between 2001 and 2003 with 65 children aged 2-8 years and their mothers in Britain. Mothers were interviewed about children's diabetes care, nutritional analyses were conducted and mothers completed assessments of diabetes knowledge, parenting stress, family functioning and child psychological adjustment. Demographic and medical information was collected from patient records. FINDINGS: Consistent with older populations, blood glucose monitoring and dietary regimens showed greater adherence variability than injection frequency and injection time consistency. Better maternal diabetes knowledge correlated with less injection time variability, more frequent blood glucose monitoring, lower percentage energy intake from extrinsic sugars, lower glycosylated haemoglobin levels and fewer relationship difficulties. Longer diabetes duration, greater injection time variability and higher percentage energy intake from extrinsic sugars predicted less frequent blood glucose monitoring. More relationship difficulties and less frequent blood glucose monitoring predicted higher percentage energy intake from extrinsic sugars. CONCLUSIONS: Nurses can facilitate treatment adherence through provision of educational, practical and socio-emotional support. Nursing interventions should target blood glucose monitoring and dietary regimens in particular, and nurses should be sensitive to the various caretaking challenges presented to parents by different components of the diabetes regimen. PMID- 17284278 TI - Can nurses help identify patients with depression following stroke? A pilot study using two methods of detection. AB - AIM: This paper reports a study to determine the accuracy of the Geriatric Mental State examination and the Montgomery-Asberg Depression Rating Scale, when administered by a nurse, in detecting depression in patients who have recently had a stroke. BACKGROUND: After a stroke, survivors spend considerable amounts of time in the direct care of nurses. Many show signs of depression, and this has been associated with an adverse effect on recovery and rehabilitation. Identifying those with depression when they have communication and cognitive difficulties is especially difficult. Treatments are available to assist in the management of depression, and early detection and intervention may assist in this process. METHOD: A cross-sectional pilot study was conducted, comparing (a) clinical diagnosis of depression by a psychiatrist with (b) two clinical interviews, using the Geriatric Mental State examination and the Montgomery Asberg Depression Rating Scale, conducted by a nurse. The data were collected in 2002. FINDINGS: Twenty-eight patients, who were still in hospital in the second week poststroke, were included. The median age was 72 (interquartile range: 61 78). There were 14 males. The psychiatrist rated seven (25%) patients as depressed. The Geriatric Mental State examination had a sensitivity of 71%, a specificity of 67%, a positive predictive value of 42%, a negative predictive value of 88% in detecting depression and an overall efficiency of 68%. The Montgomery-Asberg Depression Rating Scale had a sensitivity of 100%, a specificity of 65%, a positive predictive value of 54%, a negative predictive value of 100% and an overall efficiency of 75%. CONCLUSION: In this study, the Geriatric Mental State examination and the Montgomery-Asberg Depression Rating Scale were at least as efficient at detecting the depression in patients who have had a stroke. However, as the Montgomery-Asberg Depression Rating Scale is quicker to administer, it may prove more useful to nurses clinically. PMID- 17284279 TI - Reconsidering the conceptualization of nursing workload: literature review. AB - AIM: This paper reports a literature review that aimed to analyse the way in which nursing intensity and patient dependency have been considered to be conceptually similar to nursing workload, and to propose a model to show how these concepts actually differ in both theoretical and practical terms. BACKGROUND: The literature on nursing workload considers the concepts of patient 'dependency' and nursing 'intensity' in the realm of nursing workload. These concepts differ by definition but are used to measure the same phenomenon, i.e. nursing workload. METHOD: The literature search was undertaken in 2004 using electronic databases, reference lists and other available literature. Papers were sourced from the Medline, Psychlit, CINAHL and Cochrane databases and through the general search engine Google. The keywords focussed on nursing workload, nursing intensity and patient dependency. FINDINGS: Nursing work and workload concepts and labels are defined and measured in different and often contradictory ways. It is vitally important to understand these differences when using such conceptualizations to measure nursing workload. A preliminary model is put forward to clarify the relationships between nursing workload concepts. CONCLUSION: In presenting a preliminary model of nursing workload, it is hoped that nursing workload might be better understood so that it becomes more visible and recognizable. Increasing the visibility of nursing workload should have a positive impact on nursing workload management and on the provision of patient care. PMID- 17284280 TI - Participation in health-promoting behaviour: influences on community-dwelling older Chinese people. AB - AIM: This paper reports a study to determine the factors affecting community dwelling older Chinese people's health-promoting behaviour in the domains of physical activity, healthy dietary practices and stress management, and to identify any barriers to these behaviours. BACKGROUND: Previous studies have identified factors affecting different types of health-promoting behaviours, including perceived self-efficacy, perceived benefits and five individual characteristics (age, sex, marital status, education and perceived health) of older non-Chinese people. However, few studies have simultaneously taken these factors into account in examining community-dwelling Chinese older people's health-promoting behaviour. METHOD: Individual face-to-face interviews were completed in 2002-2003 with a convenience sample of 896 community-dwelling older Chinese people in Hong Kong aged between the ages of 60 and 98 (years mean 76). Participants had no apparent communication and cognition impairments. A structured interview schedule was used to collect the data. RESULTS: Multiple regression analysis showed that perceived self-efficacy, perceived benefits and sex together explained 38.4% of health-promoting behaviour among community dwelling older Chinese people in Hong Kong. Fatigue during and after physical activity, enjoyment of unhealthy foods and inadequate family and peer support were the most frequently reported barriers to health-promoting behaviour. CONCLUSION: When developing health promotion programmes to motivate community dwelling older Chinese clients to participate in health-promoting behaviour and to minimize barriers, community nurses should include some activities to increase both the perceived self-efficacy and perceived benefits of health-promoting behaviour. Future studies should include more critical factors based on theories, empirical evidence and knowledge of culture with samples that are random and from more diverse community settings. PMID- 17284281 TI - Low dose of Concanavalin-A enhances innate immune response and prevents liver injury in mice infected with Candida albicans. AB - The mechanisms through which Candida albicans is recognized by immune cells and how it triggers host defence are not completely understood. In this study, we evaluated the effect of Concanavalin-A on the clearance of C. albicans by infected mice and their production of proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Subgroups of 5 animals were pretreated with Con-A (250 mug mL(-1) PBS) and after 96 h were infected intraperitoneally with 10(7) cells of C. albicans CR15 (an isolate from a HIV+ person); 30 min, 2, 6, 24 or 72 h after infection the mice were sacrificed. Phagocytosis of C. albicans by peritoneal macrophages increased 30 min after infection in mice pretreated with Con-A. The liver presented the greatest number of CFUs, and this number was reduced by pretreatment with Con-A. Control animals infected with C. albicans presented a significant increase in plasmatic alanine aminotransferase, which was not observed in mice treated with Con-A. Two hours after infection the production of TNF-alpha in the liver of mice pretreated with Con-A was significantly increased. These results suggest that a single dose of Con-A caused a beneficial modulating action of the inflammatory response during infection with C. albicans. PMID- 17284283 TI - Stent-stabilization of left ventricular pacing leads for cardiac resynchronization therapy: a promising concept? PMID- 17284282 TI - DNA repair profiles of disease-associated isolates of Neisseria meningitidis. AB - Neisseria meningitidis, or the meningococcus, is the source of significant morbidity and mortality in humans worldwide. Even though mutability has been linked to the occurrence of outbreaks of epidemic disease, meningococcal DNA repair pathways are poorly delineated. For the first time, a collection of meningococcal disease-associated isolates has been demonstrated to express constitutively the DNA glycosylases MutY and Fpg in vivo. DNA sequence analysis showed considerable variability in the deduced amino acid sequences of MutS and Fpg, while MutY and RecA were highly conserved. Interestingly, multi-locus sequence typing demonstrated a putative link between the pattern of amino acid substitutions and levels of spontaneous mutagenicity in meningococcal strains. These results provide a basis for further studies aimed at resolving the genotype/phenotype relationships of meningococcal genome variability and mutator activity. PMID- 17284284 TI - In cardiac resynchronization therapy: should we opt for AV optimization? PMID- 17284285 TI - Unraveling the mysteries of catheter ablation for atrial fibrillation: from clinical observations to mechanistic explorations. PMID- 17284286 TI - Preliminary results with percutaneous transcatheter microwave ablation of typical atrial flutter. AB - BACKGROUND: Linear microwave ablation has been shown to be effective for treatment of atrial fibrillation during open-heart surgery by producing transmural lesions in the atrium to isolate the pulmonary veins. However, the safety and efficacy of percutaneous, transcatheter, linear microwave ablation for atrial arrhythmias, while demonstrated in animal models, is unknown in humans. Therefore, we studied the safety and efficacy of linear microwave ablation of the cavotricuspid isthmus (CTI) in humans with typical atrial flutter, utilizing a 2 cm long microwave antenna mounted on a steerable 9-French catheter. METHODS AND RESULTS: In seven consecutive patients, multielectrode catheters were positioned at the His bundle (quadripolar) and around the TV annulus (duo-decapolar) for pacing and recording atrial activation sequence before and after ablation. The microwave antenna was withdrawn gradually from tricuspid annulus towards inferior vena cava to ablate the CTI. Intracardiac ultrasound was used to ensure adequate endocardial contact of the microwave ablation catheter with the CTI. Microwave energy was applied at a power of 18 to 21 W at each ablation point for 120 seconds. Ablation was repeated until bidirectional CTI block was confirmed by demonstrating a descending activation wavefront in the contralateral atrial wall during pacing from the coronary sinus ostium or low lateral right atrium, respectively. Bidirectional isthmus block was achieved in all patients, after a mean number of 27.4 +/- 14.7 energy applications per patients. There were no acute procedural complications. CONCLUSIONS: Percutaneous, transcatheter microwave ablation of CTI dependent atrial flutter was demonstrated to be safe and effective in this preliminary feasibility study. PMID- 17284287 TI - Transthoracic tissue Doppler imaging of the atria to determine atrial fibrillation cycle length. PMID- 17284288 TI - Ambulatory electrocardiographic monitoring: has mobile cardiac outpatient telemetry changed the playing field? PMID- 17284290 TI - Electrical noise artifact: from without or within? PMID- 17284289 TI - The pacemaker current: from basics to the clinics. AB - Activation of the pacemaker ("funny," I(f)) current during diastole is the main process underlying generation of the diastolic depolarization and spontaneous activity of cardiac pacemaker cells. I(f) modulation by autonomic transmitters is responsible for the chronotropic regulation of heart rate. Given its role in pacemaking, I(f) has been a major target of investigation aimed to exploit its rate-controlling function in a clinical perspective. In this short review, we describe some of the most recent clinically relevant applications of the concept of I(f)-based pacemaking. PMID- 17284291 TI - Temporal variability of atrial fibrillation in pacemaker recipients for bradycardia: implications for crossover designed trials, study sample size, and identification of responder patients by means of arrhythmia burden. AB - BACKGROUND: Most clinical trials that have tested pacing therapies to prevent and treat atrial tachyarrhythmias (AT) have chosen endpoints such as AT frequency or burden (defined as percentage of time a patient is in AT), but failed to show unequivocal evidence of a clinical impact. AIM: The aim of our multicenter prospective observational study was to measure the variability of AT burden and estimate its impact on study outcomes. METHODS AND RESULTS: Two hundred and fifty patients indicated for permanent pacing and suffering from AT (age 71 +/- 9 years; 47.2% male) received a dual-chamber pacemaker. AT burden was measured in two consecutive, 2-month observation periods; the Monte Carlo method was then applied to simulate findings of a crossover design study. We simulated several models of therapy impact, each model being characterized by the percentage of responder patients and the percentage reduction in AT burden. To show a significant impact of AT therapies in a sample of 250 patients in whom 100, 75, or 50% would be theoretical responders to therapies, AT burden reduction should be at least 27, 32, or 57%, respectively. Temporal fluctuations in AT burden were so high that about 60% of patients would falsely appear as responders or nonresponders in a crossover study, regardless of AT burden reduction. CONCLUSIONS: In patients paced for bradycardia and suffering from AT, high intrapatient variability in AT burden was measured. Various models of therapy impact showed that, in crossover trials of AT therapies, time-related fluctuations in AT burden negatively impact on sample sizes and impair the ability to identify patients as responders or nonresponders. PMID- 17284292 TI - Rapamycin: brain excitability studied in vitro. AB - Neurological complications are common in transplant recipients treated with immunosuppressant calcineurin inhibitors. Rapamycin, a macrolide antibiotic, was suggested as an alternative agent in patients who develop calcineurin inhibitor associated neurotoxicity, including seizure attacks. The aim of the present study was to test the effect of rapamycin on the bioelectrical activity and evoked field excitatory postsynaptic potentials (fEPSP) in CA1 area of hippocampal tissues and compare its effect with FK506, a calcineurin inhibitor agent. Application of rapamycin at different concentrations neither affected the bioelectrical activity nor changed fEPSP magnitude. In contrast, FK506 elicited epileptiform burst discharges and significantly enhanced fEPSP magnitude. This study supports the suggestion that rapamycin could be used as an alternative to calcineurin inhibitors in the event of neurotoxicity. PMID- 17284294 TI - Effect of interictal spikes on single-cell firing patterns in the hippocampus. AB - PURPOSE: The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. METHODS: We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. RESULTS: IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. CONCLUSIONS: This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner. PMID- 17284293 TI - Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. AB - PURPOSE: The present study explores the hypothesis that the antiepileptic mechanism of action of levetiracetam (LEV) is related to effects on alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels in mouse cortical neurons in culture. METHODS: The neurons were subjected to the whole cell configuration of the patch-clamp recording technique and were 8-12 days old in culture. RESULTS: Kainate elicited concentration-dependent (EC(50)= 80 microM) inward currents in all the patched cells. LEV (5-200 microM) itself did not induce inward or outward currents on all patched neurons, whereas it was effective on the kainate- and AMPA-induced current because it significantly decreased the amplitude of these currents. LEV was also able to significantly decrease the total membrane conductance during kainate perfusion, indicating that its effect was not dependent on the cellular voltage membrane potential. Further evidence that LEV modulated the ionotropic non-NMDA receptors came from the analysis of miniature excitatory postsynaptic currents (mEPSCs). In fact, LEV significantly decreased both the amplitude and the frequency of mEPSCs, as shown by the relative cumulative distributions. CONCLUSIONS: These results reveal that AMPA receptors are modulated by LEV because a significant decrease in the kainate and AMPA-induced currents and a decrease in amplitude and in frequency of mEPSCs have been observed in cortical neurons in culture. The described effect of LEV on AMPA receptors in cortical neurons is probably due to the etheromeric composition of the receptors and may be considered as a possible new antiepileptic mechanism of action. PMID- 17284295 TI - A comparison of self-reported quality of life between patients with epilepsy and neurocardiogenic syncope. AB - Epilepsy and neurocardiogenic syncope share a final common pathway of loss of consciousness and consequent social disruption. We compared 52 patients with syncope, 96 with epilepsy and 100 controls. Epilepsy and syncope patients expressed significantly higher levels of anxiety and depression and reported significantly less good quality of life (QoL) compared with controls. There were no significant differences on any of the QoL parameters measured between the syncope and epilepsy patients. These findings suggest the main contributor to poor QoL in epilepsy may be the unpredictable loss of control that is the hallmark of the condition. PMID- 17284296 TI - Postoperative recovery of hippocampal contralateral diffusivity in medial temporal lobe epilepsy. AB - PURPOSE: To search for a recovery after surgery of mean diffusivity (MD) values in the contralateral nonsclerotic hippocampus of patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). METHODS: Twenty-four MTLE patients (12 right-sided and 12 left-sided MTLE) and 36 healthy volunteers were investigated using diffusion tensor imaging. A region-of-interest approach was used to measure pre- and postoperative interictal hippocampal MD values in patients. RESULTS: Diffusion abnormalities in contralateral nonsclerotic hippocampus recovered after surgery (p<0.0001). A subgroup of 14 patients exhibited a clear increase in MD values whereas the remaining 10 patients were stable. No significant difference was found between the two subgroups for each of the electroclinical data studied including early postoperative outcome, all patients being either seizure free or with rare persistent auras. CONCLUSIONS: This finding suggests that diffusion abnormalities in contralateral hippocampus may represent a functional mechanism linked to the active epileptic process. PMID- 17284297 TI - Postsurgical health-related quality of life (HRQOL) in children following hemispherectomy for intractable epilepsy. AB - Health-related quality of life (HRQOL) is an important outcome measure in clinical research. Given the psychosocial and behavioral difficulties associated with pediatric epilepsy, evaluating HRQOL in this patient population is of particular importance. Though HRQOL has been examined in pediatric patients receiving focal resection or pharmacological (antiepileptic drug; AED) treatment, it has not been assessed in patients receiving hemispherectomy (HE) for intractable epilepsy. The current study evaluated HRQOL in a sample of pediatric HE cases (N=26) using previously validated questionnaires relative to surgical (N=30) and nonsurgical (N=84) comparison groups. Compared with focal resection and nonsurgical patients, parents of children who received HE reported similar levels of HRQOL. In surgical cases, worse HRQOL was correlated with residual seizure frequency. In both surgical and nonsurgical cases, female gender, higher AED load, and lower functional independence predicted worse HRQOL. Interestingly, HE status (i.e., having undergone HE) predicted fewer epilepsy-related limitations. Consistent with previous findings, AED load, in addition to lower functional abilities, appear particularly detrimental to life quality in pediatric epilepsy. HE, however, is not associated with increased risk for poor HRQOL. When considered in light of the multiple, significant risk factors for poor outcome associated with HE, children who undergo the procedure fare surprisingly well. PMID- 17284298 TI - Mood, personality, and health-related quality of life in epileptic and psychogenic seizure disorders. AB - PURPOSE: Patients with psychogenic nonepileptic seizures (PNES) rate their health related quality of life (HRQOL) more poorly than those with epileptic seizures (ES). This has been explained in part by mood state. We sought to investigate whether HRQOL differences between diagnostic groups (PNES vs. ES) can be explained by additional, perhaps chronic, aspects of mood and personality. An understanding of these relationships may inform treatment designed to improve HRQOL in ES or PNES. METHODS: One-hundred fourteen individuals (69 ES and 45 PNES) completed the quality of life in Epilepsy-89. The profile of mood states (POMS) and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) were employed to measure current and chronic mood symptoms, respectively. Multiple regression analyses determined the contribution of chronic mood symptoms to HRQOL beyond the variance accounted for by current mood state and seizure diagnosis. RESULTS: Similar to previous reports, individuals with PNES reported poorer HRQOL than those with ES. Current mood state was strongly related to HRQOL and appeared to moderate the relationship between seizure diagnosis and HRQOL. However, when more chronic psychological symptoms, such as somatization and emotional distress, were included in a model, the moderating role of mood state was not significant. CONCLUSION: Analyzed independently, mood state is related to HRQOL, but when chronic indicators of psychological symptoms are included in a model mood is related to HRQOL, but, the moderating effect of mood is no longer significant. Treatments designed to improve HRQOL among individuals with intractable seizures should also address chronic psychological distress and symptoms associated with high levels of somatization. PMID- 17284299 TI - Levetiracetam and felbamate interact both pharmacodynamically and pharmacokinetically: an isobolographic analysis in the mouse maximal electroshock model. AB - PURPOSE: Polytherapy with two or more antiepileptic drugs (AEDs) is generally required for approximately 30% of patients with epilepsy, who do not respond satisfactorily to monotherapy. The potential usefulness of AED combinations, producing synergistic anticonvulsant efficacy and minimal adverse effects, is therefore of significant importance. The present study sought to ascertain the potential usefulness of levetiracetam (LEV) and felbamate (FBM) in combination in the mouse maximal electroshock (MES)-induced seizure model. METHODS: The anticonvulsant interaction profile between LEV and FBM in the mouse MES-induced seizure model was determined using type II isobolographic analysis. Acute adverse effects (motor performance) were ascertained by use of the chimney test. LEV and FBM brain concentrations were measured by HPLC in order to determine any pharmacokinetic contribution to the observed antiseizure effect. RESULTS: LEV in combination with FBM, at the fixed ratios of 1:2, 1:1, 2:1, and 4:1, were supraadditive, whereas at the fixed ratio of 1:4, additivity was observed in the mouse MES model. Furthermore, none of the investigated combinations altered motor performance in the chimney test. Brain FBM concentrations were unaffected by concomitant LEV administration. In contrast, FBM significantly increased LEV brain concentrations. CONCLUSIONS: LEV in combination with FBM was associated with pharmacodynamic supraadditivity in the MES test. However, this anticonvulsant supraadditivity was associated with a concurrent increase in brain LEV concentrations indicating a pharmacokinetic contribution to the observed pharmacodynamic interaction between LEV and FBM. PMID- 17284301 TI - The Liverpool Adverse Events Profile: relation to AED use and mood. AB - PURPOSE: The Liverpool Adverse Events Profile (LAEP) is used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). This study evaluated LAEP in newly diagnosed seizure patients, and examined the relation between LAEP, anxiety, and depression. METHODS: Seizure patients seen in the two First Seizure Clinics were categorized into group A (AEDs commenced after assessment), group B (AEDs commenced before assessment), and group C (no AEDs). LAEP and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline (n=164) and 3 months (n=103). Each LAEP symptom was assessed for baseline frequency, 3-month frequency, and frequency change over a 3-month period. Global scores for LAEP and HADS were analysed at baseline and 3 months. RESULTS: Symptom-reporting patterns were similar between groups. However, increased frequency over a 3-month period occurred for 12 symptoms in group A, 10 in group B, and one in group C. Global LAEP and HADS showed no significant group differences at baseline or changes over a 3-month period. Multiple regression revealed that HADS scores predicted LAEP global scores better than did AED status. Multivariate analyses of variance demonstrated that increased reporting of 16 of 19 LAEP symptoms was significantly related to higher anxiety and depression rates. CONCLUSIONS: In a First Seizure Clinic, LAEP detects changes in specific symptom frequencies when used as a repeated, symptom-by-symptom measure. Increased symptom frequency is associated with diagnostic category/AED treatment, anxiety, and depression. Global LAEP scores do not illustrate differences in symptom reporting between patients. PMID- 17284300 TI - Pediatric language mapping: sensitivity of neurostimulation and Wada testing in epilepsy surgery. AB - PURPOSE: Functional mapping of eloquent cortex with electrical neurostimulation is used both intra- and extraoperatively to tailor resections. In pediatric patients, however, functional mapping studies frequently fail to localize language. Wada testing has also been reported to be less sensitive in children. METHODS: Thirty children (4.7 - 14.9 years) and 18 adult controls (18-59 years) who underwent extraoperative language mapping via implanted subdural electrodes at the NYU Comprehensive Epilepsy Center were included in the study. Ten children and 14 adults underwent preoperative Wada testing. Success of the procedures was defined as the identification of at least one language site by neurostimulation mapping and determination of hemispheric language dominance on the Wada test. RESULTS: In children younger than 10.2 years, cortical stimulation identified language cortex at a lower rate than was seen in children older than 10.2 years and in adults (p<0.05). This threshold, demonstrated by survival and chi2 analysis, was sharply defined in our data set. Additionally, Wada testing was more likely to be successful than was extraoperative mapping in this younger age group (p<0.05). CONCLUSIONS: Analysis of our series demonstrates that language cortex is less likely to be identified in children younger than 10 years, suggesting that alternatives to the current methods of cortical electrical stimulation, particularly the use of preoperative language lateralization, may be required in this age group. PMID- 17284302 TI - Altered distribution of KCC2 in cortical dysplasia in patients with intractable epilepsy. AB - PURPOSE: To examine the distribution of KCC2, a neuron-specific K(+)-Cl(-) cotransporter, in human cortical dysplasia (CD). METHODS: The immunohistochemical expression of KCC2 was investigated in 18 CD specimens obtained during epilepsy surgery. The histopathologic diagnoses were focal CD (FCD) type I (eight cases), FCD type II (six cases), and hemimegalencephaly (HME; four cases). Tissue sections were immunostained for KCC2 and compared with control sections. RESULTS: In the mature nondysplastic cortex, all the layers showed diffuse neuropil staining for KCC2. The somata were stained much less, although subcortical ectopic neurons displayed dense staining in the cytosol (intrasomatic staining). In FCD type I, the cortex showed neuropil staining for KCC2 with less-stained somata. Aberrant giant pyramidal neurons were also less stained at the soma, whereas immature neurons showed intrasomatic staining. Increased numbers of ectopic neurons with intrasomatic staining were noted in the subcortical white matter. In FCD type II, dysmorphic neurons displayed dense intrasomatic staining with reduced staining of the neighboring neuropils. Balloon cells did not stain for KCC2. Dysmorphic neurons in HME also showed intrasomatic staining. CONCLUSIONS: Neurons in CD tissues expressed KCC2. However, the subcellular distribution of KCC2 was altered, which might have affected the ionic homeostasis of Cl(-) and K(+) involved in epileptic activity within CD tissues. PMID- 17284304 TI - Shining light on lupus and UV. AB - People exposed to sunlight can develop erythema, DNA damage, and photoimmunosupression. Extended exposure of normal epidermis to sunlight will induce dysmorphic keratinocytes with pyknotic nuclei scattered throughout the spinous layer. These 'sunburn cells' are apoptotic keratinocytes and are usually cleared within 48 hours after sunburn. Patients with lupus erythematosus, however, whether it be the discoid, subacute cutaneous, systemic, or tumid form, develop new cutaneous lesions and can experience systemic worsening of their disease. Are sunlight-induced keratinocyte apoptosis and the immune response to these cells abnormal in lupus patients? PMID- 17284303 TI - Immunomodulatory properties of mesenchymal stem cells: a review based on an interdisciplinary meeting held at the Kennedy Institute of Rheumatology Division, London, UK, 31 October 2005. AB - Multipotent mesenchymal stromal cells isolated from bone marrow and other sites are currently being studied to determine their potential role in the pathogenesis and/or management of autoimmune diseases. In vitro studies have shown that they exhibit a dose-dependent antiproliferative effect on T and B lymphocytes, dendritic cells, natural killer cells and various B cell tumour lines--an effect that is both cell contact and soluble factor dependent. Animal models of autoimmune disease treated with multipotent mesenchymal stromal cells have mostly exhibited a positive clinical response, as have a limited number of patients suffering from acute graft versus host disease. This review summarizes the findings of a 1-day meeting devoted to the subject with the aim of coordinating efforts. PMID- 17284305 TI - Carbon dioxide removal device: how long is long enough? PMID- 17284306 TI - Extracorporeal liver support: a continuing challenge. AB - Given that liver failure continues to pose an enormous clinical challenge, the concept of hepatic dialysis has enjoyed significant interest. In particular, many investigations have examined the therapeutic mechanisms and efficacy of artificial albumin dialysis based systems in acute on chronic liver failure, the results of which have been conflicting. Albumin dialysis systems do not appear to significantly decrease serum concentrations of inflammatory cytokines in severe acute on chronic liver failure. Thus, if these treatments do result in clinical improvement, then other therapeutic mechanisms must be involved. PMID- 17284308 TI - Coexistence of splenic marginal zone lymphoma with hepatocellular carcinoma: a case report. AB - BACKGROUND: Coexistence of splenic marginal zone lymphoma with hepatocellular carcinoma is rare. Although some reports have suggested the possible pathogenic role of HBV, HCV, chronic and persistent antigenic stimulation in lymphoma, their role in causing lymphomas is still unclear. CASE PRESENTATION: We describe a hepatocellular carcinoma with concomitant splenic marginal zone lymphoma in a 64 year-old Chinese man with cirrhosis. Serum hepatitis B virus surface antigen was positive and antihepatitis C virus antibody was negative. The resected liver mass measuring 4 x 3 x 3 cm was grey and soft with a small area of bleeding, necrosis and intact capsule. Cut surface of the spleen was red-purple and had a diffuse reticulonodular appearance indicative of prominent white pulp. On histologic sections, the liver mass was well and moderately differentiated hepatocellular carcinoma, and the splenic tumor was a specific low-grade small B-cell lymphoma. Immunohistochemical staining and gene rearrangement studies supported that the splenic tumor represents a clonal B-cell lymphoma. Therefore, the diagnosis of SMZL was made from the splenic specimen. CONCLUSION: To our knowledge, this is the second case report describing coexistence of hepatocellular carcinoma and splenic marginal zone lymphoma in the course of chronic HBV infection. However, we cannot assert at present that hepatitis B virus is directly involved in splenic lymphomagenesis until more information is collected from more cases in the future. PMID- 17284307 TI - Hemodynamic responses in human multisensory and auditory association cortex to purely visual stimulation. AB - BACKGROUND: Recent findings of a tight coupling between visual and auditory association cortices during multisensory perception in monkeys and humans raise the question whether consistent paired presentation of simple visual and auditory stimuli prompts conditioned responses in unimodal auditory regions or multimodal association cortex once visual stimuli are presented in isolation in a post conditioning run. To address this issue fifteen healthy participants partook in a "silent" sparse temporal event-related fMRI study. In the first (visual control) habituation phase they were presented with briefly red flashing visual stimuli. In the second (auditory control) habituation phase they heard brief telephone ringing. In the third (conditioning) phase we coincidently presented the visual stimulus (CS) paired with the auditory stimulus (UCS). In the fourth phase participants either viewed flashes paired with the auditory stimulus (maintenance, CS-) or viewed the visual stimulus in isolation (extinction, CS+) according to a 5:10 partial reinforcement schedule. The participants had no other task than attending to the stimuli and indicating the end of each trial by pressing a button. RESULTS: During unpaired visual presentations (preceding and following the paired presentation) we observed significant brain responses beyond primary visual cortex in the bilateral posterior auditory association cortex (planum temporale, planum parietale) and in the right superior temporal sulcus whereas the primary auditory regions were not involved. By contrast, the activity in auditory core regions was markedly larger when participants were presented with auditory stimuli. CONCLUSION: These results demonstrate involvement of multisensory and auditory association areas in perception of unimodal visual stimulation which may reflect the instantaneous forming of multisensory associations and cannot be attributed to sensation of an auditory event. More importantly, we are able to show that brain responses in multisensory cortices do not necessarily emerge from associative learning but even occur spontaneously to simple visual stimulation. PMID- 17284309 TI - Persistent hyperglycemia is an independent predictor of outcome in acute myocardial infarction. AB - BACKGROUND: Elevated blood glucose values are a prognostic factor in myocardial infarction (MI) patients. The unfavourable relation between hyperglycemia and outcome is known for admission glucose and fasting glucose after admission. These predictors are single measurements and thus not indicative of overall hyperglycemia. Increased persistent hyperglycemia may better predict adverse events in MI patients. METHODS: In a prospective study of MI patients treated with primary percutaneous coronary intervention (PCI) frequent blood glucose measurements were obtained to investigate the relation between glucose and the occurrence of major adverse cardiac events (MACE) at 30 days follow-up. MACE was defined as death, recurrent infarction, repeat primary coronary intervention, and left ventricular ejection fraction equal to or smaller than 30%. RESULTS: MACE occurred in 89 (21.3%) out 417 patients. In 17 patients (4.1%) it was a fatal event. A mean of 7.4 glucose determinations were available per patient. Mean +/- SD admission glucose was 10.1 +/- 3.7 mmol/L in patients with a MACE versus 9.1 +/- 2.7 mmol/L in event-free patients (P = 0.0024). Mean glucose during the first two days after admission was 9.0 +/- 2.8 mmol/L in patients with MACE compared to 8.1 +/- 2.0 mmol/L in event free patients (P < 0.0001). The area under the receiver operator characteristic curve was 0.64 for persistent hyperglycemia and 0.59 for admission glucose. Persistent hyperglycemia emerged as a significant independent predictor (P < 0.001). CONCLUSION: Persistent hyperglycemia in MI has a stronger relation with 30-day MACE than elevated glucose at admission. PMID- 17284310 TI - Relating a calcium indicator signal to the unperturbed calcium concentration time course. AB - BACKGROUND: Optical indicators of cytosolic calcium levels have become important experimental tools in systems and cellular neuroscience. Indicators are known to interfere with intracellular calcium levels by acting as additional buffers, and this may strongly alter the time-course of various dynamical variables to be measured. RESULTS: By investigating the underlying reaction kinetics, we show that in some ranges of kinetic parameters one can explicitly link the time dependent indicator signal to the time-course of the calcium influx, and thus, to the unperturbed calcium level had there been no indicator in the cell. PMID- 17284311 TI - Female philopatry in a heterogeneous environment: ordinary conditions leading to extraordinary ESS sex ratios. AB - BACKGROUND: We use a simulation-based model to study the impact of female philopatry and heterogeneity of habitat quality on the evolution of primary sex ratio. RESULTS: We show that these conditions may lead to strongly biased ESS habitat-dependent sex ratios, under two kinds of density-dependent population regulation. ESS sex ratios are always biased towards females in good habitats, towards males in poor habitats, and are generally equilibrated considering the whole population. Noticeably, the predicted bias of sex ratio usually increases with decreasing female philopatry. CONCLUSION: The selection forces responsible for these results are fully described. This study provides a new perspective on the evolutionary significance of temperature sex determination. We discuss the case of turtles by comparing our theoretical results with field observations. PMID- 17284313 TI - FUNC: a package for detecting significant associations between gene sets and ontological annotations. AB - BACKGROUND: Genome-wide expression, sequence and association studies typically yield large sets of gene candidates, which must then be further analysed and interpreted. Information about these genes is increasingly being captured and organized in ontologies, such as the Gene Ontology. Relationships between the gene sets identified by experimental methods and biological knowledge can be made explicit and used in the interpretation of results. However, it is often difficult to assess the statistical significance of such analyses since many inter-dependent categories are tested simultaneously. RESULTS: We developed the program package FUNC that includes and expands on currently available methods to identify significant associations between gene sets and ontological annotations. Implemented are several tests in particular well suited for genome wide sequence comparisons, estimates of the family-wise error rate, the false discovery rate, a sensitive estimator of the global significance of the results and an algorithm to reduce the complexity of the results. CONCLUSION: FUNC is a versatile and useful tool for the analysis of genome-wide data. It is freely available under the GPL license and also accessible via a web service. PMID- 17284312 TI - Reduced efficacy of selection in regions of the Drosophila genome that lack crossing over. AB - BACKGROUND: The recombinational environment is predicted to influence patterns of protein sequence evolution through the effects of Hill-Robertson interference among linked sites subject to selection. In freely recombining regions of the genome, selection should more effectively incorporate new beneficial mutations, and eliminate deleterious ones, than in regions with low rates of genetic recombination. RESULTS: We examined the effects of recombinational environment on patterns of evolution using a genome-wide comparison of Drosophila melanogaster and D. yakuba. In regions of the genome with no crossing over, we find elevated divergence at nonsynonymous sites and in long introns, a virtual absence of codon usage bias, and an increase in gene length. However, we find little evidence for differences in patterns of evolution between regions with high, intermediate, and low crossover frequencies. In addition, genes on the fourth chromosome exhibit more extreme deviations from regions with crossing over than do other, no crossover genes outside the fourth chromosome. CONCLUSION: All of the patterns observed are consistent with a severe reduction in the efficacy of selection in the absence of crossing over, resulting in the accumulation of deleterious mutations in these regions. Our results also suggest that even a very low frequency of crossing over may be enough to maintain the efficacy of selection. PMID- 17284315 TI - Host habitat assessment by a parasitoid using fungal volatiles. AB - BACKGROUND: The preference-performance hypothesis predicts that oviposition preference of insects should correlate with host suitability for offspring development. Therefore, insect females have to be able to assess not only the quality of a given host but also the environmental conditions of the respective host habitat. Chemical cues are a major source of information used by insects for this purpose. Primary infestation of stored grain by stored product pests often favors the intense growth of mold. This can lead to distinct sites of extreme environmental conditions (hot-spots) with increased insect mortality. We studied the influence of mold on chemical orientation, host recognition, and fitness of Lariophagus distinguendus, a parasitoid of beetle larvae developing in stored grain. RESULTS: Volatiles of wheat infested by Aspergillus sydowii and A. versicolor repelled female parasitoids in an olfactometer. Foraging L. distinguendus females are known to be strongly attracted to the odor of larval host feces from the granary weevil Sitophilus granarius, which may adhere in remarkable amounts to the surface of the grains. Feces from moldy weevil cultures elicited neutral responses but parasitoids clearly avoided moldy feces when non moldy feces were offered simultaneously. The common fungal volatile 1-octen-3-ol was the major component of the odor of larval feces from moldy weevil cultures and repelled female parasitoids at naturally occurring doses. In bioassays investigating host recognition behavior of L. distinguendus, females spent less time on grains containing hosts from moldy weevil cultures and showed less drumming and drilling behavior than on non-moldy controls. L. distinguendus had a clearly reduced fitness on hosts from moldy weevil cultures. CONCLUSION: We conclude that L. distinguendus females use 1-octen-3-ol for host habitat assessment to avoid negative fitness consequences due to secondary mold infestation of host patches. The female response to fungal volatiles is innate, suggesting that host-associated fungi played a crucial role in the evolution of host finding strategies of L. distinguendus. Research on the role of host associated microorganisms in the chemically mediated orientation of parasitoids is still at the beginning. We expect an increasing recognition of this issue in the future. PMID- 17284314 TI - ArhGAP9, a novel MAP kinase docking protein, inhibits Erk and p38 activation through WW domain binding. AB - We have identified human ArhGAP9 as a novel MAP kinase docking protein that interacts with Erk2 and p38alpha through complementarily charged residues in the WW domain of ArhGAP9 and the CD domains of Erk2 and p38alpha. This interaction sequesters the MAP kinases in their inactive states through displacement of MAP kinase kinases targeting the same sites. While over-expression of wild type ArhGAP9 caused MAP kinase activation by the epidermal growth factor receptor (EGFR) to be suppressed and preserved the actin stress fibres in quiescent Swiss 3T3 fibroblasts, over-expression of an ArhGAP9 mutant defective in MAP kinase binding restored EGFR-induced MAP kinase activation and resulted in significant disruption of the stress fibres, consistent with the role of Erk activation in disassembly of actin stress fibres. The interaction between ArhGAP9 and the MAP kinases represents a novel mechanism of cross-talk between Rho GTPase and MAP kinase signaling. PMID- 17284317 TI - Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis. AB - Preclinical osteoarthritis (OA) models are often employed in studies investigating disease-modifying OA drugs (DMOADs). In this study we present a comprehensive, longitudinal evaluation of OA pathogenesis in a rat model of OA, including histologic and biochemical analyses of articular cartilage degradation and assessment of subchondral bone sclerosis. Male Sprague-Dawley rats underwent joint destabilization surgery by anterior cruciate ligament transection and partial medial meniscectomy. The contralateral joint was evaluated as a secondary treatment, and sham surgery was performed in a separate group of animals (controls). Furthermore, the effects of walking on a rotating cylinder (to force mobilization of the joint) on OA pathogenesis were assessed. Destabilization induced OA was investigated at several time points up to 20 weeks after surgery using Osteoarthritis Research Society International histopathology scores, in vivo micro-computed tomography (CT) volumetric bone mineral density analysis, and biochemical analysis of type II collagen breakdown using the CTX II biomarker. Expression of hypertrophic chondrocyte markers was also assessed in articular cartilage. Cartilage degradation, subchondral changes, and subchondral bone loss were observed as early as 2 weeks after surgery, with considerable correlation to that seen in human OA. We found excellent correlation between histologic changes and micro-CT analysis of underlying bone, which reflected properties of human OA, and identified additional molecular changes that enhance our understanding of OA pathogenesis. Interestingly, forced mobilization exercise accelerated OA progression. Minor OA activity was also observed in the contralateral joint, including proteoglycan loss. Finally, we observed increased chondrocyte hypertrophy during pathogenesis. We conclude that forced mobilization accelerates OA damage in the destabilized joint. This surgical model of OA with forced mobilization is suitable for longitudinal preclinical studies, and it is well adapted for investigation of both early and late stages of OA. The time course of OA progression can be modulated through the use of forced mobilization. PMID- 17284318 TI - Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain. AB - The etiology of osteoarthritis is multifactorial, with inflammatory, metabolic, and mechanical causes. Pain in osteoarthritis is initiated by mild intra articular inflammation and degeneration of articular cartilage and subchondral bone. The principle of treatment with acetaminophen or non-steroidal anti inflammatory drugs is to reduce pain and improve joint function. Recently, animal models for osteoarthritic pain behavior have been established. The most frequently used rat model for analyzing properties of drugs on the pathology of osteoarthritis is the injection of the metabolic inhibitor monosodium iodoacetate into the joint, which inhibits the activity of glyceraldehyde-3-phosphate dehydrogenase in chondrocytes. Here, we characterize the effect on pain behavior of lacosamide, a member of a family of functionalized amino acids that are analogues of endogenous amino acids and D-serine, in the monosodium iodoacetate rat model for osteoarthritis in comparison to diclofenac and morphine. Lacosamide (3, 10, and 30 mg/kg) was able to reduce secondary mechanical allodynia and hyperalgesia similarly to morphine (3 mg/kg). In contrast, diclofenac (30 mg/kg) was only effective in reducing secondary mechanical hyperalgesia. During the first week, pain is induced mainly by inflammation in the iodoacetate model, but afterwards inflammation plays only a minor role in pain. Lacosamide was able to inhibit pain at days 3, 7 and 14 after induction of arthritis. This shows that lacosamide is able to reduce pain behavior induced by multiple mechanisms in animals. PMID- 17284319 TI - A first generation BAC-based physical map of the channel catfish genome. AB - BACKGROUND: Channel catfish, Ictalurus punctatus, is the leading species in North American aquaculture. Genetic improvement of catfish is performed through selective breeding, and genomic tools will help improve selection efficiency. A physical map is needed to integrate the genetic map with the karyotype and to support fine mapping of phenotypic trait alleles such as Quantitative Trait Loci (QTL) and the effective positional cloning of genes. RESULTS: A genome-wide physical map of the channel catfish was constructed by High-Information-Content Fingerprinting (HICF) of 46,548 Bacterial Artificial Chromosomes (BAC) clones using the SNaPshot technique. The clones were assembled into contigs with FPC software. The resulting assembly contained 1,782 contigs and covered an estimated physical length of 0.93 Gb. The validity of the assembly was demonstrated by 1) anchoring 19 of the largest contigs to the microsatellite linkage map 2) comparing the assembly of a multi-gene family to Restriction Fragment Length Polymorphism (RFLP) patterns seen in Southern blots, and 3) contig sequencing. CONCLUSION: This is the first physical map for channel catfish. The HICF technique allowed the project to be finished with a limited amount of human resource in a high throughput manner. This physical map will greatly facilitate the detailed study of many different genomic regions in channel catfish, and the positional cloning of genes controlling economically important production traits. PMID- 17284316 TI - Corynebacterium endocarditis species-specific risk factors and outcomes. AB - BACKGROUND: Corynebacterium species are recognized as uncommon agents of endocarditis, but little is known regarding species-specific risk factors and outcomes in Corynebacterium endocarditis. METHODS: Case report and Medline search of English language journals for cases of Corynebacterium endocarditis. Inclusion criteria required that cases be identified as endocarditis, having persistent Corynebacterium bacteremia, murmurs described by the authors as identifying the affected valve, or vegetations found by echocardiography or in surgical or autopsy specimens. Cases also required patient-specific information on risk factors and outcomes (age, gender, prior prosthetic valve, other prior nosocomial risk factors (infected valve, involvement of native versus prosthetic valve, need for valve replacement, and death) to be included in the analysis. Publications of Corynebacterium endocarditis which reported aggregate data were excluded. Univariate analysis was conducted with chi-square and t-tests, as appropriate, with p = 0.05 considered significant. RESULTS: 129 cases of Corynebacterium endocarditis involving nine species met inclusion criteria. Corynebacterium endocarditis typically infects the left heart of adult males and nearly one third of patients have underlying valvular disease. One quarter of patients required valve replacement and one half of patients died. Toxigenic C. diphtheriae is associated with pediatric infections (p < 0.001). Only C. amycolatum has a predilection for women (p = 0.024), while C. pseudodiphtheriticum infections are most frequent in men (p = 0.023). C. striatum, C. jeikeium and C. hemolyticum are associated with nosocomial risk factors (p < 0.001, 0.028, and 0.024, respectively). No species was found to have a predilection for any particular heart valve. C. pseudodiphtheriticum is associated with a previous prosthetic valve replacement (p = 0.004). C. jeikeium infections are more likely to require valve replacement (p = 0.026). Infections involving toxigenic C. diphtheriae and C. pseudodiphtheriticum are associated with decreased survival (p = 0.001 and 0.032, respectively). CONCLUSION: We report the first analysis of species specific risk factors and outcomes in Corynebacterium endocarditis. In addition to species-specific associations with age, gender, prior valvular diseases, and other nosocomial risk factors, we found differences in rates of need for valve replacement and death. This review highlights the seriousness of these infections, as up to 28% of patients required valve replacement and 43.5% died. PMID- 17284321 TI - The improved Clinical Global Impression Scale (iCGI): development and validation in depression. AB - BACKGROUND: The Clinical Global Impression scale (CGI) is frequently used in medical care and clinical research because of its face validity and practicability. This study proposes to improve the reliability of the Clinical Global Impression (CGI) scale in depressive disorders by the use of a semi standardized interview, a new response format, and a Delphi procedure. METHODS: Thirty patients hospitalised for a major depressive episode were filmed at T1 (first week in hospital) and at T2 (2 weeks later) during a 5' specific interview. The Hamilton Depressive Rating Scale and the Symptom Check List were also rated. Eleven psychiatrists rated these videos using either the usual CGI response format or an improved response format, with or without a Delphi procedure. RESULTS: The new response format slightly improved (but not significantly) the interrater agreement, the Delphi procedure did not. The best results were obtained when ratings by 4 independent raters were averaged. In this situation, intraclass correlation coefficients were about 0.9. CONCLUSION: The Clinical Global Impression is a useful approach in psychiatry since it apprehends patients in their entirety. This study shows that it is possible to quantify such impressions with a high level of interrater agreement. PMID- 17284320 TI - A case-control study of GST polymorphisms and arsenic related skin lesions. AB - BACKGROUND: Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. Individual factors in arsenic biotransformation may influence disease susceptibility. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates. METHODS: We investigated whether polymorphisms in GSTT1, GSTP1 and GSTM1 were associated with risk of skin lesions and whether these polymorphisms modify the relationship between drinking water arsenic exposure and skin lesions in a case control study of 1200 subjects frequency matched on age and gender in community clinics in Pabna, Bangladesh in 2001-2002. RESULTS AND DISCUSSION: GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status (OR1.56 95% CI 1.10-2.19). The GSTP1 GG polymorphism was associated with greater odds of skin lesions compared to GSTP1 AA, (OR 1.86 (95%CI 1.15-3.00). No evidence of effect modification by GSTT1, GSTM1 or GSTP1 polymorphisms on the association between arsenic exposure and skin lesions was detected. CONCLUSION: GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions. PMID- 17284322 TI - A pilot study on acupuncture for lower urinary tract symptoms related to chronic prostatitis/chronic pelvic pain. AB - BACKGROUND: The etiology and treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remain poorly understood. Pain, lower urinary tract voiding symptoms and negative impact on quality of life (QOL) are the most common complaints. Acupuncture, which has been widely used to treat painful and chronic conditions, may be a potential treatment to alleviate the constellation of symptoms experienced by men with CP/CPPS. The purpose of our study was to assess the impact of standardized full body and auricular acupuncture in men refractory to conventional therapies and collect pilot data to warrant further randomized trials. METHODS: Ten men diagnosed with category IIIA or IIIB CP/CPPS >6 months, refractory to at least 1 conventional therapy (antibiotics, anti-inflammatory agents, 5-alpha reductase inhibitors, alpha-1 blockers) and scoring >4 on the pain subset of the NIH-CPSI were prospectively analyzed in an Institutional Review Board (IRB) approved, single-center clinical trial (Columbia University Medical Center IRB#AAAA-7460). Standardized full body and auricular acupuncture treatment was given twice weekly for 6 weeks. The primary endpoints were total score of the NIH-CPSI and assessment of serious adverse events. The secondary endpoints were individual scores of the NIH-CPSI and QOL questionnaire scores of the short-form 36 (SF-36). RESULTS: The median age of the subjects was 36 years (range 29-63). Decreases in total NIH-CPSI scores (mean +/- SD) after 3 and 6 weeks from baseline (25.1 +/- 6.6) were 17.6 +/- 5.7 (P < 0.006) and 8.8 +/- 6.2 (P < 0.006) respectively and remained significant after an additional 6 weeks of follow-up (P < 0.006). Symptom and QOL/NIH-CPSI sub-scores were also significant (P < 0.002 and P < 0.002 respectively). Significance in 6 of 8 categories of the SF-36 including bodily pain (P < 0.002) was achieved. One regression in the SF-36 vitality category was observed after follow-up. There were no adverse events. CONCLUSION: The preliminary findings, although limited, suggest the potential therapeutic role of acupuncture in the treatment of CP/CPPS. Data from this and previous studies warrant randomized trials of acupuncture for CP/CPPS and particular attention towards acupuncture point selection, treatment intervention, and durability of acupuncture. PMID- 17284323 TI - Manipulation of cell cycle progression can counteract the apparent loss of correction frequency following oligonucleotide-directed gene repair. AB - BACKGROUND: Single-stranded oligonucleotides (ssODN) are used routinely to direct specific base alterations within mammalian genomes that result in the restoration of a functional gene. Despite success with the technique, recent studies have revealed that following repair events, correction frequencies decrease as a function of time, possibly due to a sustained activation of damage response signals in corrected cells that lead to a selective stalling. In this study, we use thymidine to slow down the replication rate to enhance repair frequency and to maintain substantial levels of correction over time. RESULTS: First, we utilized thymidine to arrest cells in G1 and released the cells into S phase, at which point specific ssODNs direct the highest level of correction. Next, we devised a protocol in which cells are maintained in thymidine following the repair reaction, in which the replication is slowed in both corrected and non corrected cells and the initial correction frequency is retained. We also present evidence that cells enter a senescence state upon prolonged treatment with thymidine but this passage can be avoided by removing thymidine at 48 hours. CONCLUSION: Taken together, we believe that thymidine may be used in a therapeutic fashion to enable the maintenance of high levels of treated cells bearing repaired genes. PMID- 17284324 TI - Effective healthcare teams require effective team members: defining teamwork competencies. AB - BACKGROUND: Although effective teamwork has been consistently identified as a requirement for enhanced clinical outcomes in the provision of healthcare, there is limited knowledge of what makes health professionals effective team members, and even less information on how to develop skills for teamwork. This study identified critical teamwork competencies for health service managers. METHODS: Members of a state branch of the professional association of Australian health service managers participated in a teamwork survey. RESULTS: The 37% response rate enabled identification of a management teamwork competency set comprising leadership, knowledge of organizational goals and strategies and organizational commitment, respect for others, commitment to working collaboratively and to achieving a quality outcome. CONCLUSION: Although not part of the research question the data suggested that the competencies for effective teamwork are perceived to be different for management and clinical teams, and there are differences in the perceptions of effective teamwork competencies between male and female health service managers. This study adds to the growing evidence that the focus on individual skill development and individual accountability and achievement that results from existing models of health professional training, and which is continually reinforced by human resource management practices within healthcare systems, is not consistent with the competencies required for effective teamwork. PMID- 17284326 TI - Schmeissneria: a missing link to angiosperms? AB - BACKGROUND: The origin of angiosperms has been under debate since the time of Darwin. While there has been much speculation in past decades about pre Cretaceous angiosperms, including Archaefructus, these reports are controversial. The earliest reliable fossil record of angiosperms remains restricted to the Cretaceous, even though recent molecular phylogenetic studies suggest an origin for angiosperms much earlier than the current fossil record. RESULTS: In this paper, after careful SEM and light microscopic work, we report fossils with angiospermous traits of the Jurassic age. The fossils were collected from the Haifanggou Formation (middle Jurassic) in western Liaoning, northeast China. They include two female structures and an associated leaf on the same slab. One of the female structures is physically connected to the apex of a short shoot. The female organs are borne in pairs on short peduncles that are arranged along the axis of the female structure. Each of the female organs has a central unit that is surrounded by an envelope with characteristic longitudinal ribs. Each central unit has two locules completely separated by a vertical septum. The apex of the central unit is completely closed. The general morphology places these fossils into the scope of Schmeissneria, an early Jurassic genus that was previously attributed to Ginkgoales. CONCLUSION: Because the closed carpel is a character only found in angiosperms, the closed apex of the central unit suggests the presence of angiospermy in Schmeissneria. This angiospermous trait implies either a Jurassic angiosperm or a new seed plant group parallel to angiosperms and other known seed plants. As an angiosperm, the Liassic age (earliest Jurassic) of Schmeissneria microstachys would suggest an origin of angiosperms during the Triassic. Although still uncertain, this could have a great impact on our perspective of the history, diversity and systematics of seed plants and angiosperms. PMID- 17284325 TI - Therapy for pneumonitis and sialadenitis by accumulation of CCR2-expressing CD4+CD25+ regulatory T cells in MRL/lpr mice. AB - Adoptive transfer of CD4+CD25+ regulatory T cells has been shown to have therapeutic effects in animal models of autoimmune diseases. Chemokines play an important role in the development of autoimmune diseases in animal models and humans. The present study was performed to investigate whether the progression of organ-specific autoimmune diseases could be reduced more markedly by accumulating chemokine receptor-expressing CD4+CD25+ regulatory T cells efficiently in target organs in MRL/MpJ-lpr/lpr (MRL/lpr) mice. CD4+CD25+Foxp3+ T cells (Treg cells) and CD4+CD25+Foxp3+ CCR2-transfected T cells (CCR2-Treg cells) were transferred via retro-orbital injection into 12-week-old MRL/lpr mice at the early stage of pneumonitis and sialadenitis, and the pathological changes were evaluated. Expression of monocyte chemoattractant protein-1 (MCP-1)/CCL2 was observed in the lung and submandibular gland of the mice and increased age-dependently. The level of CCR2 expression and MCP-1 chemotactic activity of CCR2-Treg cells were much higher than those of Treg cells. MRL/lpr mice to which CCR2-Treg cells had been transferred showed significantly reduced progression of pneumonitis and sialadenitis in comparison with MRL/lpr mice that had received Treg cells. This was due to more pronounced migration of CCR2-Treg cells and their localization for a longer time in MCP-1-expressing lung and submandibular gland, resulting in stronger suppressive activity. We prepared chemokine receptor-expressing Treg cells and demonstrated their ability to ameliorate disease progression by accumulating in target organs. This method may provide a new therapeutic approach for organ-specific autoimmune diseases in which the target antigens remain undefined. PMID- 17284327 TI - No genetic evidence for involvement of Deltaretroviruses in adult patients with precursor and mature T-cell neoplasms. AB - BACKGROUND: The Deltaretrovirus genus comprises viruses that infect humans (HTLV), various simian species (STLV) and cattle (BLV). HTLV-I is the main causative agent in adult T-cell leukemia in endemic areas and some of the simian T-cell lymphotropic viruses have been implicated in the induction of malignant lymphomas in their hosts. BLV causes enzootic bovine leukosis in infected cattle or sheep. During the past few years several new Deltaretrovirus isolates have been described in various primate species. Two new HTLV-like viruses in humans have recently been identified and provisionally termed HTLV-III and HTLV-IV. In order to identify a broad spectrum of Deltaretroviruses by a single PCR approach we have established a novel consensus PCR based on nucleotide sequence data obtained from 42 complete virus isolates (HTLV-I/-II, STLV-I/-II/-III, BLV). The primer sequences were based on highly interspecies-conserved virus genome regions. We used this PCR to detect Deltaretroviruses in samples from adult patients with a variety of rare T-cell neoplasms in Germany. RESULTS: The sensitivity of the consensus PCR was at least between 10-2 and 10-3 with 100% specificity as demonstrated by serial dilutions of cell lines infected with either HTLV-I, HTLV-II or BLV. Fifty acute T-cell lymphoblastic leukemia (T-ALL) samples and 33 samples from patients with various rare mature T-cell neoplasms (T PLL, Sezary syndrome and other T-NHL) were subsequently investigated. There were no cases with HTLV-I, HTLV-II or any other Deltaretroviruses. CONCLUSION: The results rule out a significant involvement of HTLV-I or HTLV-II in these disease entities and show that other related Deltaretroviruses are not likely to be involved. The newly established Deltaretrovirus PCR may be a useful tool for identifying new Deltaretroviruses. PMID- 17284328 TI - Immunological responses can have both pro- and antitumour effects: implications for immunotherapy. AB - Immune responses influence the development and progression of a malignancy. The tumour can also manipulate the immune system to its own ends, often resulting in an ineffective or transient antitumour response. An appreciation of the complexity of these host-tumour interactions is therefore important for the development of more-effective cancer therapies. This article highlights some prominent mechanisms whereby tumours escape recognition and destruction by the host immune system, thus facilitating disease progression. One important consequence of tumour escape is that an antitumour immune response may unintentionally lead to the outgrowth of less immunogenic or more apoptosis resistant tumour escape variants, which possess enhanced tumourigenic potential. Insights into the molecular mechanisms of cancer evasion and the complexity of the ever-changing interactions between host and tumour will enable a more rational design of antitumour therapies and may help not only explain disease recurrence, but also identify potential targets for therapeutic interventions. This article also offers a brief review of preclinical animal models, which are essential tools in the study of tumour immunology and cancer biology, particularly those that recapitulate the chronic nature of host-tumour interactions and help guide the development and testing of new therapies. PMID- 17284329 TI - AT1 receptor blocker-insensitive mutant AT1A angiotensin receptors reveal the presence of G protein-independent signaling in C9 cells. AB - Although mutant receptors are highly useful to dissect the signal transduction pathways of receptors, they are difficult to study in physiological target tissues, due to the presence of endogenous receptors. To study AT(1) angiotensin receptors in their physiological environment, we constructed a mutant receptor, which differs only from the AT(1A) receptor in its reduced affinity for candesartan, a biphenylimidazole antagonist. We have determined that the conserved S109Y substitution of the rat AT(1A) receptor eliminates its candesartan binding, without exerting any major effect on its angiotensin II and peptide angiotensin receptor antagonist binding, internalization kinetics, beta arrestin binding, and potency or efficacy of the inositol phosphate response. To demonstrate the usefulness of this mutant receptor in signal transduction studies, we combined it with substitution of the highly conserved DRY sequence with AAY, which abolishes G protein activation. In rat C9 hepatocytes the S109Y receptor caused ERK activation with the same mechanism as the endogenous AT(1) receptor. After combination with the DRY/AAY mutation G protein-independent ERK activation was detected demonstrating that this approach can be used to study the angiotensin II-stimulated signaling pathways in cells endogenously expressing AT(1) receptors. PMID- 17284331 TI - The Pech-de-l'Aze I Neandertal child: ESR, uranium-series, and AMS 14C dating of its MTA type B context. AB - The Pech-de-l'Aze I skull and mandible are included in the juvenile Neandertal remains from Europe. However, some preserved features in the cranial skeleton seem to distinguish the specimen from other Neandertal children. Unfortunately, the stratigraphic position and dating of this child has never been clear. Our recent work on unpublished archives show that the Pech-de-l'Aze I Neandertal child was discovered at the bottom of layer 6, attributed to the Mousterian of Acheulean tradition type B. These skull and mandible are the first diagnostic human remains (aside from an isolated tooth) attributed to the Mousterian of Acheulian tradition (MTA) type B. Consequently, we confirm that Neandertals were the makers of this Mousterian industry, which is characterized by unusual high frequencies of Upper Paleolithic type tools, elongated blanks and blades. We were able to date the context of the hominid remains by dating layer 6 and the layers above and beneath it using ESR, coupled ESR/(230)Th/(234)U (coupled ESR/U series), and AMS (14)C. Coupled ESR/U-series results on 16 mammalian teeth constrain the age of the uppermost layer 7 to 41-58ka, and layer 6 to 37-51ka. The wide spread in each age estimate results mainly from uncertainties in the gamma-dose rate. These ages are concordant with AMS (14)C ages of two bones coming from the top of layer 6, which provide dates of about 41.7-43.6ka cal BP. A combination of stratigraphic arguments and dating results for layers 6 and 7 show that the Neandertal child cannot be older than 51ka or younger than 41ka. The lowermost layer 4 is shown to be older than 43ka by the principle of superposition and ESR dating in the immediately overlying layer 5. This study shows that the MTA type B had been manufactured by Neandertals before the arrival of anatomically modern humans in the local region. Additionally, by providing a firm chronological framework for the specific morphometric the features of Pech de-l'Aze I Neandertal child, this study is a new step toward the understanding of temporal and spatial changes in the ontogenesis of Neandertals in south-western Europe during oxygen isotope stages 5-3. PMID- 17284332 TI - Postnatal exposure to octylphenol decreases semen quality in the adult ram. AB - The aim of this experiment was to determine if maternal exposure to octylphenol pre- and/or postnatally influenced FSH concentrations and semen quantity and quality in postpubertal rams. Rams were born to ewes that received twice-weekly s.c. injections of octylphenol equivalent to 1000microg/kg/day for one of the following periods: (1) day 70 of gestation (D70) to weaning (at 20 weeks postnatally; n=4); (2) D70 to birth (n=6); (3) birth to weaning (n=7), controls received corn oil from D70 to weaning (n=5). Rams were blood-sampled weekly and semen characteristics were evaluated at 1 year of age. Maternal exposure to octylphenol, pre- and/or postnatally did not affect FSH concentrations, semen volume, concentration, percentage live, motility or IVM/IVF characteristics. However, exposure to octylphenol from birth to weaning increased the number of morphologically abnormal sperm cells in the ejaculates of these rams. PMID- 17284333 TI - Plasma progesterone and prolactin concentrations in overtly pseudopregnant bitches: a clinical study. AB - Plasma concentrations of progesterone (P(4)) and prolactin (PRL) were measured in 35 bitches presented at veterinary clinics for symptoms of overt pseudopregnancy (PSP) between 50 and 95 days after the onset of proestrus. Results were compared to those from samples collected from 35 control bitches at comparable stages of the ovarian cycle (expressed as days after the onset of observed signs of proestrus). In the PSP bitches at 71.4+/-1.6 (mean+/-S.E.M.) days of the cycle, P(4) (1.5+/-0.2ng/mL) was lower (P<0.01) and PRL (16.0+/-1.9ng/mL) was higher (P<0.01), compared to P(4) (2.7+/-0.4ng/mL) and PRL (2.9+/-0.6ng/mL) in control bitches at 70.6+/-1.5 days of the cycle. Low P(4) was not a prerequisite for elevated PRL. Although elevated (> or =10ng/mL) PRL (20.9+/-2.0ng/mL) occurred more often with low (<2ng/mL) P(4) (20 of 24 cases) it also occurred with P(4) above 3ng/mL in two affected bitches and in two control bitches. Whether the occurrence of relatively low PRL concentrations (<4ng/mL) in samples obtained from 4 of the 35 pseudopregnant bitches reflected variable and often elevated PRL secretion or increased sensitivity to PRL in the absence of elevated prolactin in those animals was not determined. We inferred that elevated plasma PRL was often involved in the etiology of overt PSP; furthermore, a premature decline in circulating P(4) concentrations may be a factor in some instances. PMID- 17284330 TI - CAR and PXR: the xenobiotic-sensing receptors. AB - The xenobiotic receptors CAR and PXR constitute two important members of the NR1I nuclear receptor family. They function as sensors of toxic byproducts derived from endogenous metabolism and of exogenous chemicals, in order to enhance their elimination. This unique function of CAR and PXR sets them apart from the steroid hormone receptors. In contrast, the steroid receptors, exemplified by the estrogen receptor (ER) and glucocorticoid receptor (GR), are the sensors that tightly monitor and respond to changes in circulating steroid hormone levels to maintain body homeostasis. This divergence of the chemical- and steroid-sensing functions has evolved to ensure the fidelity of the steroid hormone endocrine regulation while allowing development of metabolic elimination pathways for xenobiotics. The development of the xenobiotic receptors CAR and PXR also reflect the increasing complexity of metabolism in higher organisms, which necessitate novel mechanisms for handling and eliminating metabolic by-products and foreign compounds from the body. The purpose of this review is to discuss similarities and differences between the xenobiotic receptors CAR and PXR with the prototypical steroid hormone receptors ER and GR. Interesting differences in structure explain in part the divergence in function and activation mechanisms of CAR/PXR from ER/GR. In addition, the physiological roles of CAR and PXR will be reviewed, with discussion of interactions of CAR and PXR with endocrine signaling pathways. PMID- 17284335 TI - Expression of inducible CC chemokines in rainbow trout (Oncorhynchus mykiss) in response to a viral haemorrhagic septicemia virus (VHSV) DNA vaccine and interleukin 8. AB - In rainbow trout (Oncorhynchus mykiss), at least three CXC chemokines and eighteen CC chemokine sequences have been discovered in the past years, although no studies concerning their bioactivity have been performed yet. We have studied the expression of five different CC chemokines that cluster into the group of inducible chemokines (CK5A, CK5B, CK6, CK7A and CK7B) in trout injected with a plasmid coding for the glycoprotein G gene (pMCV1.4-G) of viral haemorrhagic septicemia virus (VHSV). In a previous work, we had demonstrated that a plasmid coding for the CXC chemokine interleukin 8 (IL-8, pIL8+) when co-administered with pMCV1.4-G was able to modulate the expression of induced pro-inflammatory cytokines, therefore, we have also studied the expression of these inducible CC chemokines in fish injected with pMCV1.4-G in the presence of pIL8+, study that will also help establish the relations among the different chemokine groups. All chemokines were induced in the head kidney of fish injected with the DNA vaccine, and the co-administration of pIL8+ together with the vaccine modulated the expression of all CC chemokines studied. In this sense, expression of the inducible CC chemokines was also studied in trout head kidney leucocytes treated with supernatants from EPC cells transfected with pIL8+. In this case, all CC chemokines studied except for CK5B were significantly induced by rainbow trout IL 8. PMID- 17284334 TI - Calcium influx mediated by the inwardly rectifying K+ channel Kir4.1 (KCNJ10) at low external K+ concentration. AB - COS-1 cells with heterologeous expression of the Kir4.1 (KCNJ10) channel subunit, possess functional Kir4.1 channels and become capable to generating cytosolic Ca2+ transients, upon lowering of the extracellular K+ concentration to 2 mM or below. These Ca2+ transients are blocked by external Ba2+ (100 microM). Acute brain stem slices from wild-type mice (second post-natal week), which were loaded with the fluorescent Ca2+ indicator Oregon Green BAPTA-1-AM, were exposed to 0.2 mM K+. Under these conditions astrocytes, but not neurons, responded with cytosolic Ca2+ elevations in wild-type mice. This astrocyte-specific response has previously been used to identify astroglial cells type [R. Dallwig, H. Vitten, J.W. Deitmer, A novel barium-sensitive calcium influx into rat astrocytes at low external potassium. Cell Calcium 28 (2000) 247-259]. In Kir4.1 knock-out (Kir4.1 /-) mice, the number of responding cells was dramatically reduced and the Ca2+ transients in responding cells were significantly smaller than in wild-type mice. Our results indicate that Kir4.1 channels are the molecular substrate for the observed Ca2+ influx in astrocytes under conditions of low external K+ concentration. PMID- 17284336 TI - Studies of twins in vaccinology. AB - In this survey, we review published investigations and trials of vaccines among twins. We identified 29 original studies, dating back to 1979. The studies include determinations of the role of genetics and environment in the variation in immune response to vaccination, the investigation of adverse events in which vaccination was the suspected etiologic agent, and the occurrence of vaccine preventable diseases or their complications. Specific methods include case reports, cross-sectional surveys, prospective surveys, and double-blind, randomized, placebo-controlled, cross-over studies. We examine three of these studies in detail to illustrate important opportunities and limitations of twins studies in vaccinology. PMID- 17284338 TI - Gingival liposarcoma: an unusual polyp. AB - Liposarcomas account for up to 20% of all soft tissue tumours. They are uncommon in the head and neck. Sarcomas of the oral region (excluding lymphoma) account for 5% of all oral cancers, of which 10% are liposarcomas. Fewer than 80 cases have been reported in the world literature, most of which presented as expansile masses. The prognosis of liposarcoma is dependant on the histopathologic type, location, and adequacy of surgical treatment. Well-differentiated types have a good prognosis and minimal metastatic potential. We report a case of well differentiated liposarcoma (lipoma-like subtype), that presented as a gingival polyp. PMID- 17284337 TI - Parental attitudes to pre-pubertal HPV vaccination. AB - OBJECTIVES: To determine the acceptability of childhood HPV vaccination and examine demographic, cultural, and psychosocial predictors of vaccine acceptance. DESIGN: School-based survey. PARTICIPANTS: Questionnaires sent to 1205 mothers of 8-14-year-old girls. Responses from 684 were included in the analyses. SETTING: Ten schools (seven primary, three secondary) in four areas of England. RESULTS: Seventy-five percent of mothers would accept the vaccine for their daughter. Vaccine acceptance was higher in mothers who had experience of cancer in the family (OR=1.61, CI: 1.14-2.29), had older daughters (OR=1.15, CI: 1.04-1.27), perceived approval from husband/partner (OR=14.51, CI: 6.15-34.25) and believed vaccine acceptance would be more normative (OR=1.78, CI: 1.59-2.01). Having concerns about too many vaccinations (OR=0.22, CI: 0.15-0.31) or vaccine side effects (OR=0.37, CI: 0.28-0.50) and worry about increasing promiscuity (OR=0.47, CI: 0.36-0.62) emerged as deterrents. The modal preferred age was 12 years. Endorsing vaccination at earlier ages was predicted by feeling able to discuss related topics, including sex, at younger ages (OR=1.37, CI: 1.24-1.51) and concern about increasing promiscuity (OR=0.61, CI: 0.47-0.78). CONCLUSIONS: Overall, there was a favourable response to HPV vaccination. Emphasising the widespread acceptance of the vaccine might promote acceptance further, as would information on immunological and social benefits of earlier vaccination. PMID- 17284339 TI - The enhancement of the energetic efficiency by the cooperation of low-efficient flashing ratchets. AB - The energetic efficiency of the classical flashing ratchet model is much lower (around 1%) than the experimental results (around 50%). Julicher and Prost have provided a prototype of the cooperative ratchet model [Julicher, F., Prost, J., 1995. Cooperative molecular motors. Phys. Rev. Lett. 75, 2618-2621], whose energetic efficiency is of the order of 50%. However, it remains an unsettled question how the low-efficient flashing ratchets cooperate with each other and achieve higher energetic efficiency. In this paper, we investigate two energy dissipation rates as well as the energetic efficiency for the single and the cooperative flashing ratchet model, close to and far from the equilibrium, based on the stochastic energetics. By comparing these quantities between the single and the cooperative ratchet, we provide an interpretation of the efficiency enhancement by the cooperation of low-efficient flashing ratchets. PMID- 17284340 TI - Controlling the ratchet effect through the symmetries of the systems: application to molecular motors. AB - We discuss a novel generic mechanism for controlling the ratchet effect through the breaking of relevant symmetries. We review previous works on ratchets where directed transport is induced by the breaking of standard temporal symmetries f(t)=-f(t+T/2) and f(t)=f(-t) (or f(t)=-f(-t)). We find that in seemingly unrelated systems the average velocity (or the current) of particles (or solitons) exhibits common features. We show that, as a consequence of Curie's symmetry principle, the average velocity (or the current) is related to the breaking of the symmetries of the system. This relationship allows us to control the transport in a systematic way. The qualitative agreement between the present analytical predictions and previous experimental, numerical, and theoretical results leads us to suggest that for the given breaking of the temporal symmetries there is an optimal wave form for a given time-periodic force. Also, we comment on how this mechanism can be applied to the case where a ratchet effect is induced by breaking of spatial symmetries. Finally, we conjecture that the ratchet potential underlying biological motor proteins might be optimized according to the breaking of the relevant symmetries. PMID- 17284341 TI - Variability and randomness in stationary neuronal activity. AB - The patterns of neuronal activity can be different even if the mean firing rate is fixed. Investigating the variability of the firing may not be sufficient and we suggest to take into account the notion of randomness. The randomness is related to the entropy of the firing, which is bounded from above by the entropy of the Poisson process (given the mean interspike interval). Thus, we propose the Kullback-Leibler distance with respect to the Poisson process as a measure of randomness in a stationary neuronal activity. Under the condition of equal mean values the KL distance does not depend on the time scale and therefore can be compared to the coefficient of variation employed to measure the variability. Furthermore, this measure can be extended to account for correlated neuronal firing. Finally, we analyze the variability and randomness for three common ISI distributions in detail: gamma, lognormal and inverse Gaussian. PMID- 17284342 TI - Optimal signal in sensory neurons under an extended rate coding concept. AB - We define an optimal signal in parametric neuronal models on the basis of interspike interval data and rate coding schema. Under the classical approach the optimal signal is located where the frequency transfer function is steepest. Its position coincides with the inflection point of this curve. This concept is extended here by using Fisher information which is the inverse asymptotic variance of the best estimator and its dependence on the parameter value indicates accuracy of estimation. We compare the signal producing maximal Fisher information with the inflection point of the sigmoidal frequency transfer function. PMID- 17284343 TI - Density dependent neurodynamics. AB - The dynamics of a neural network depends on density parameters at (at least) two different levels: the subcellular density of ion channels in single neurons, and the density of cells and synapses at a network level. For the Frankenhaeuser Huxley (FH) neural model, the density of sodium (Na) and potassium (K) channels determines the behaviour of a single neuron when exposed to an external stimulus. The features of the onset of single neuron oscillations vary qualitatively among different regions in the channel density plane. At a network level, the density of neurons is reflected in the global connectivity. We study the relation between the two density levels in a network of oscillatory FH neurons, by qualitatively distinguishing between three regions, where the mean network activity is (1) spiking, (2) oscillating with enveloped frequencies, and (3) bursting, respectively. We demonstrate that the global activity can be shifted between regions by changing either the density of ion channels at the subcellular level, or the connectivity at the network level, suggesting that different underlying mechanisms can explain similar global phenomena. Finally, we model a possible effect of anaesthesia by blocking specific inhibitory ion channels. PMID- 17284344 TI - Modelling the early steps of transduction in insect olfactory receptor neurons. AB - Olfactory transduction is a multistep process whose basic function is to convert a low energy reaction, the odorant-receptor interaction that may involve a single odorant molecule, into a whole cell electrical response, the receptor potential, which triggers the firing of one or more action potentials. Although much effort has been devoted to the experimental analysis of transduction in olfactory receptor neurons (ORNS), especially in the favorable moth sex-pheromone receptor neuron, its modelling is less advanced. The model we investigated, which takes into account the translocation of pheromone molecules from air to the extracellular space, their deactivation and their interaction with receptors, focuses on the membrane cascade. It involves the interaction of receptors, G proteins and effector enzymes, whose reaction rates are limited by lateral diffusion in the membrane. The evolutions in time of these species in response to single pulse stimulation of various intensities were compared to one another and to the experimentally measured electrical response. The results obtained suggest that the receptor-to-effector conversion is fast with respect to the receptor response, that it presents a small amplification factor, contrary to the photoreceptor, and that most of the amplification is achieved in the post effector processes involving the second messenger and ionic channels. PMID- 17284345 TI - An experimental design to optimize the flow extraction parameters for the selective removal of Fe(III) and Al(III) in aqueous samples using salicylic acid grafted on Amberlite XAD-4 and final determination by GF-AAS. AB - In this paper, a multivariable approach has been applied for the selective removing of Fe(III) and Al(III), in the range 0-200 microg l(-1), in water samples onto a modified organic support (salicylic acid grafted on XAD-4). An empirical mathematical model was designed which establishes the relationship between the variation of the responses (extraction yields), and the variation of three factors (sample volume, sample percolation flow rate and amount of metallic ions present in the sample). To estimate the coefficients of the developed model, an uniform shell Doehlert design has been applied; these experiments consisted in GF-AAS determination of aluminium and iron amounts in eluates after percolation of samples through modified support. Results show a similar behaviour of the resin towards aluminium and iron with a preponderant effect of the percolation flow rate value; however this one is crucial for aluminium extraction and should be maintained below to 0.55 ml min(-1) to reach a 95% Al3+ extraction yield (versus 2.25 ml min(-1) for Fe3+). The optima determined by this experimental design approach have been further applied to the selective extraction of aluminium and iron from multielement synthetic samples and from real samples at the outlet of potable water treatment units. PMID- 17284346 TI - Involvement of microglia in the ethanol-induced neuropathic pain-like state in the rat. AB - Central mechanisms of neuropathy induced by chronic ethanol treatment are almost unknown. In this study, rats were treated with ethanol-diet for 72 days. Mechanical hyperalgesia was observed during ethanol consumption, even after ethanol withdrawal. Under these conditions, a microglial marker ionized calcium binding adaptor molecule 1-, but not a neuron marker microtuble associated protein-2-, like immunoreactivies were increased in the rat spinal cord. Furthermore, hypertrophy of microglia was clearly observed following chronic ethanol consumption. These findings support the idea that the activation and hypertrophy of microglia in the spinal cord may be, at least in part, associated with in the induction of ethanol-dependent neuropathic pain-like state. PMID- 17284347 TI - Abnormal levels of prohibitin and ATP synthase in the substantia nigra and frontal cortex in Parkinson's disease. AB - Prohibitin and ATP synthase protein levels were examined in the substantia nigra and frontal cortex (area 8) in five cases of Parkinson's disease (PD), five cases of dementia with Lewy bodies pure form (pDLB), five cases of early Alzheimer's disease (AD stage IIA, B), nine cases with advanced AD (stages V/VIC), and nine controls. A significant reduction of prohibitin and ATP synthase was observed in the substantia nigra in PD cases. In contrast, increased prohibitin and ATP synthase levels were found in the frontal cortex in PD, and increased prohibitin but not ATP synthase in the frontal cortex in pDLB. Superoxide dismutase 2 (SOD2) expression levels were also increased in the frontal cortex in PD and pDLB. No modifications in prohibitin and ATP synthase levels were found in the frontal cortex in sporadic AD. These findings demonstrate disease-specific modifications in the expression of mitochondrial-related proteins in the frontal cortex at stages of PD in which there is no alpha-synuclein aggregation in the form of Lewy bodies and Lewy neurites in this area. These findings emphasize the presence of mitochondrial modifications before the appearance of histological hallmarks of PD, and point to the possibility of a more extended molecular pathology in PD than currently accepted. PMID- 17284349 TI - Subregions of human parietal cortex selectively encoding object orientation. AB - Computation of object orientation could be an independent process from those of other object features, but currently neither the location of human brain areas selectively coding orientation information nor an optimum experimental paradigm have yet been established. In this study, functional magnetic resonance imaging was used to investigate brain activation in the parietal cortices related to object orientation. Using an Arabic digit whose spatial attributes were carefully manipulated, we found parietal areas exclusively sensitive to object orientation, but not to general spatial attention. It seems that, by excluding confounds such as mental manipulation or working memory as well as inherent spatial information within the stimuli, functional segregation within the parietal lobe can be effectively probed. PMID- 17284348 TI - The hydroxy-methyl-glutaryl CoA reductase promoter polymorphism is associated with Alzheimer's risk and cognitive deterioration. AB - A link between cholesterol and Alzheimer's disease (AD) had been suggested. Hydroxy-methylglutaryl-coenzyme A reductase (HMGCR) is the rate limiting enzyme in the synthesis of cholesterol. A single nucleotide polymorphism (SNP) in the promoter of this gene, never described in Italian AD population, was investigated in case-control studies. Genotype distribution and allele frequency in two groups of AD patients and non demented controls were investigated. A cohort of AD patients were also followed up for 2 years, cognitive performances recorded and a possible influence of this SNP on the disease progression was tested. The CC genotype of the HMGCR gene was associated with a reduced risk of AD. Conversely the A allele of this polymorphism was over represented in AD patients. The presence of the A allele was also associated with an accelerated cognitive deterioration in AD patients followed up for 2 years. However, transfection experiments showed that this polymorphism did not directly influence functional activity in luciferase reporter gene assays. This polymorphism of the HMGCR gene appears to be linked to both AD risk and disease progression. Present findings reinforce the notion that abnormal regulation of cholesterol metabolism is a key factor in the pathogenesis of the disease. PMID- 17284350 TI - Roles of NF-kappaB and MAPK signaling pathways in morphological and cytoskeletal responses of microglia to double-stranded RNA. AB - Following virus infection of the central nervous system, microglia become activated and undergo morphological as well as functional transformations, thereby initiating effective antiviral actions. Herein, we have examined the contribution of nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways to cell shape determination and cytoskeletal organization in microglia upon stimulation with double-stranded RNA (dsRNA), a conserved molecular pattern of virus infection. Under non-proliferative condition, microglial MG6-1 cells displayed a distinctive morphology with spinescent processes and small somata. Following dsRNA stimulation, the process bearing microglial cells exhibited swift and drastic changes in cell morphology, filamentous actin (F-actin) structure, and intracellular signaling. In the dsRNA stimulated microglial cells, the activation of c-Jun N-terminal kinase (JNK) pathway was involved in morphological alteration into an ameboid state. We also found that p38 signaling pathway negatively regulates the formation of cytoplasmic vacuoles in microglial cells. Furthermore, the dsRNA-induced accumulation of F-actin was partly mediated by NF-kappaB, JNK, and p38 pathways. These results indicate that NF-kappaB and MAPK signaling pathways mediate morphological and cytoskeletal changes during dsRNA-induced microglial activation. PMID- 17284351 TI - Evaluation of a real-time polymerase chain reaction assay for rapid identification of methicillin-resistant Staphylococcus aureus directly from nasal swabs in horses. AB - Screening for nasal colonization is an important aspect of many methicillin resistant Staphylococcus aureus (MRSA) control programs. Real-time polymerase chain reaction (RT-PCR) is an attractive alternative to standard culture techniques because of the considerably shorter turnaround time. An assay has been validated for diagnostic purposes in humans, however this methodology has not been evaluated in horses. The purpose of this study was to compare an RT-PCR assay for rapid identification of MRSA directly from nasal swabs in horses to standard culture techniques. Nasal swabs collected from 293 horses were processed using a commercial RT-PCR assay (IDI-MRSA, GeneOhm Sciences, San Diego, CA) according to the manufacturer's instructions. The swabs were also cultured and MRSA was identified according to standard protocols. Initially only 176/293 samples yielded valid PCR results. Two of 176 and 167/176 samples were positive and negative, respectively, by both PCR and culture. Seven of 176 samples were positive by PCR and negative by culture, whereas 0/176 samples were negative by PCR and positive by culture. The kappa statistic was 0.35, which represented poor agreement between the tests. Of the remaining 117 samples, 105 samples were initially reported as "unresolved". Following one freeze-thaw cycle of the lysates, the recommended technique to resolve such samples, 61/110 (55%) samples remained unresolved. In this study, the IDI-MRSA assay was not a clinically practical screening test for horses harbouring nasal MRSA. Its agreement with culture was poor and the high unresolved rate (37%) also significantly decreased the clinical utility of the test. PMID- 17284352 TI - Effect of gender, age and anthropometric variables on plantar fascia thickness at different locations in asymptomatic subjects. AB - PURPOSE: The study was aimed to investigate plantar fascia thickness at different locations in healthy asymptomatic subjects and its relationship to the following variables: weight, height, sex and age. MATERIAL AND METHODS: The study evaluates 96 feet of healthy asymptomatic volunteers. The plantar fascia thickness was measured at four different locations: 1cm proximal to the insertion of the plantar fascia, at the insertion of the plantar fascia on the calcaneus and separate out 1 cm + 2 cm distal to the insertion. A 10 MHz linear-array transducer was used. RESULTS: There were statistically significant differences in plantar fascia thickness at the four different locations (p<0.001) although no differences in PF thickness were found between the two distal from insertion locations (1 and 2 cm). Multiple regression analysis showed sex as independent predictor of plantar fascia thickness at 1cm proximal to the insertion. At origin and 1cm distal to insertion weight was an independent predictor of plantar fascia thickness. CONCLUSIONS: There are differences of thickness at different locations of plantar fascia measured by ultrasonography. Thickness at 1cm proximal to the insertion is influenced by sex and thickness at origin and at 1cm distal to the insertion has a direct relationship with body weight. This could be attributed to the overloading effect that weight has on plantar fascia in healthy symptomatic subjects at these two locations. Height and age did not seem to influence as independent variables in plantar fascia thickness among non-painful subjects. PMID- 17284353 TI - A survey of neuropsychologists' beliefs and practices with respect to the assessment of effort. AB - The current study investigated neuropsychologists' beliefs and practices with respect to assessing effort and malingering by surveying a sample of NAN professional members and fellows (n=712). The results from 188 (26.4%) returned surveys indicated that 57% of respondents frequently included measures of effort when conducting a neuropsychological evaluation. While a majority of respondents (52%) rarely or never provide a warning that effort indicators will be administered, 27% of respondents often or always provide such a warning. The five most frequently used measures of effort or response bias were the Test of Memory Malingering (TOMM), MMPI-2 F-K ratio, MMPI-2 FBS, Rey 15-item test, and the California Verbal Learning Test. However, the TOMM, Validity Indicator Profile, Word Memory Test, Victoria Symptom Validity Test, and the Computerized Assessment of Response Bias were rated as most accurate for detecting suboptimal effort. These results and other findings are presented and discussed. PMID- 17284354 TI - Degrade naphthalene using cells immobilized combining with low-intensity ultrasonic technique. AB - In this paper, we studied the naphthalene degradation by using Pseudomonas aeruginosa under low-intensity ultrasonic stimulation. In our experiment, the degradation rate of naphthalene was the main parameter. We found that low intensity ultrasonic could not only promote the growth of immobilized P. aeruginosa, but also could improve the degradation of naphthalene. In this article, 1% naphthalene was added into MM culture medium as imitation wastewater. The effect of low-intensity ultrasonic parameter and gel-globes size were considered. We found the influence was obvious, and the optimum degradation rate was acquired when the parameters of ultrasonic are: frequency, 24 kHz; power, 8 W; ultrasonic time, interval time, 10 s; total time, 10 m and the gel-globes were made by using injector no. 14. The naphthalene degradation rate of immobilized cells with ultrasonic stimulation is 82%, which is 12.9 and 42.2% higher than that of immobilized cells and suspended cells without ultrasonic stimulation, respectively. PMID- 17284355 TI - Synthesis and characterization of hexa-tailed cryptand based amphiphiles: spontaneous formation of giant vesicular microcapsule with efficient and long term dye encapsulation. AB - A cryptand with six secondary amino groups has been derivatized by reacting with acid chlorides of different chain lengths (C(7), C(10) and C(18)) to get three cryptand based hexa-tailed neutral amphiphiles (L(1)-L(3)). The cavity of the cryptand head group accommodates two Cu(II) ion giving another set of three amphiphiles. These amphiphiles and its copper complexes can aggregate spontaneously as giant vesicular microcapsules in 10% ethanolic water medium. In all cases vesicles formed are mostly unilamellar in nature. Vesicular microcapsules prepared from L(1)-L(3) can encapsulate hydrophilic dye 5(6) carboxyfluorescein (CF). Stability of microcapsules, CF encapsulation efficiencies and release rates were dependent on the hydrophobic chain length of the amphiphiles. Results show the permeability of the L(2) and L(3) bilayer is lower than that of phosphatidylcholine vesicles and the loading capacity is approximately 3 times greater. Microcapsules have been characterized by optical microscopy, freeze fracture scanning electron microscopy and confocal fluorescence microscopy. PMID- 17284356 TI - Study of gelatin-agar intermolecular aggregates in the supernatant of its coacervate. AB - Intermolecular interaction leading to formation of aggregates between gelatin, a polyampholyte, and agar, a polysaccharide was studied in the supernatant of the complex coacervate formed by these biopolymers. Electrophoresis, laser light scattering and viscometry data were used to determine the interaction and the physical structure of these intermolecular soluble complexes by modeling these to be prolate ellipsoids of revolution (rod-like structures with well defined axial ratio and Perrin's factor). Solution ionic strength was found to reduce the axial ratio of these complexes implying the presence of screened polarization-induced electrostatic interaction between the two biopolymers. PMID- 17284357 TI - Selective recognition iodide in aqueous solution based on fluorescence enhancement chemosensor. AB - A novel and simple fluorescence enhancement method for selectively sensing iodide was proposed based on metal complex formation between mercuric(II) ion with fluorophore (p-((dimethylamino)benzylidene)thiosemicarbazide, 1) and with anion in aqueous solution. The 1-Hg complex was found to show selectively and sensitively fluorescence enhancement response toward iodide over than S(2-), EDTA, SCN-, CH(3)CO(2-), Br-, Cl-, F-, H2PO4- and SO4(2-), which was attributed to the higher stability of inorganic complex between iodide and mercuric(II). PMID- 17284358 TI - Synthesis and luminescent properties of the lanthanide isothiocyanate complexes with an amide-type tripodal ligand. AB - Solid complexes of lanthanide isothiocyanates with an amide-type tripodal ligand, 2,2',2''-nitrilotris-(N-phenylmethyl)-acetamide (L) have been synthesized and characterized by elemental analysis, infrared spectra and molar conductivity measurements. At the same time, the luminescent properties of the Sm(III), Eu(III), Tb(III), Dy(III) isothiocyanate complexes in solid state and the Tb(III) complex in solvents were also investigated. PMID- 17284359 TI - Therapeutic angiogenesis in the heart: protect and serve. AB - Therapeutic angiogenesis of coronary and peripheral disease has gone through a period of great hype but has now entered a rational phase. Initial clinical trials with fibroblast growth factor-2 and vascular endothelial growth factor-A have been disappointing, probably owing to suboptimal delivery and incorrect targeting. It is now understood that sustained delivery will be required and that enhancement of collateral formation, rather than angiogenesis, should be targeted. The timing of growth factor therapy might be important as most of these agents protect against ischemic and reperfusion injury, and some may favorably affect post-infarct cardiac remodeling. Preclinical testing of novel delivery strategies, combination therapy as well as novel growth factors and transcription factors pave the way for duly designed and timed clinical trials. PMID- 17284360 TI - Inverse agonism: from curiosity to accepted dogma, but is it clinically relevant? AB - Inverse agonism has gone from an initial curiosity to a now well-recognized phenomenon. This has demanded expansion of receptor theory models to account for multiple receptor states and a re-definition of ligand efficacy. However, after several decades of discovery, the clinical importance of inverse agonist ligands is still speculative because this work is founded almost exclusively on artificial systems. Although there are diseases of spontaneous constitutively active receptors, which in theory would be better suited for inverse agonist treatment, this work is still a long way from being realised. PMID- 17284361 TI - Role of acetylcholine in neurotransmission of the carotid body. AB - Acetylcholine (ACh) has been considered an important excitatory neurotransmitter in the carotid body (CB). Its physiological and pharmacological effects, metabolism, release, and receptors have been well documented in several species. Various nicotinic and muscarinic ACh receptors are present in both afferent nerve endings and glomus cells. Therefore, ACh can depolarize or hyperpolarize the cell membrane depending on the available receptor type in the vicinity. Binding of ACh to its receptor can create a wide variety of cellular responses including opening cation channels (nicotinic ACh receptor activation), releasing Ca(2+) from intracellular storage sites (via muscarinic ACh receptors), and modulating activities of K(+) and Ca(2+) channels. Interactions between ACh and other neurotransmitters (dopamine, adenosine, nitric oxide) have been known, and they may induce complicated responses. Cholinergic biology in the CB differs among species and even within the same species due to different genetic composition. Development and environment influence cholinergic biology. We discuss these issues in light of current knowledge of neuroscience. PMID- 17284363 TI - Gene amplification and expression in lung cancer cells with acquired paclitaxel resistance. AB - A paclitaxel-resistant subline was generated from the non-small lung cancer cell line NCI-H460 by stepwise selection in paclitaxel from 0.032 to 250 nmol/L. The resulting subline, designated NCI-H460/PTX250, showed 792-fold resistance against paclitaxel compared with the parental cell line NCI-H460. The chemosensitivity analysis revealed the cross-resistance phenotype against various anticancer drugs including docetaxel, vinblastine, and doxorubicin, but not against camptotecin, cisplatin, and 5-fluorouracil. The addition of 5 mumol/L verapamil or reversin 121 reversed the resistance against paclitaxel, vinblastine, and doxorubicin. The gene expression profile, examined using oligonucleotide microarrays, demonstrated that the expression of 332 and 342 genes was significantly increased and decreased, respectively, in NCI-H460/PTX250 compared with NCI-H460. The most highly upregulated gene was MDR1/ABCB1 with a 1,092-fold increase. The overexpression was confirmed at the protein level by Western blot and flow cytometry analyses. The copy number profile, examined using microarray-based comparative genomic hybridization, revealed amplification of the q11.21 approximately q21.12 region on chromosome 7. In particular, the entire q21.12 region displayed 11- to 13-fold higher copy number in NCI-H460/PTX250 than in NCI H460. Most of the genes within the region were highly expressed, and the increased expression of these genes could be explained by the amplification in the gene copy number. However, the increase in MDR1/ABCB1 expression greatly exceeded the genomic copy number increase of the gene, suggesting the existence of one or more additional factors, such as transcriptional enhancement or mRNA stabilization, associated with the elevated MDR1/ABCB1 expression. In conclusion, both chromosomal region-specific copy number amplification and gene-specific activation are probably involved in the overexpression of MDR1/ABCB1, resulting in acquisition of the drug resistance phenotype in NCI-H460/PTX250. PMID- 17284364 TI - Structural aberrations of chromosome 7 revealed by a combination of molecular cytogenetic techniques in myeloid malignancies. AB - In bone marrow cells of 33 patients with myelodysplastic syndrome and acute myeloid leukemia, structural rearrangements of chromosome 7 were found with conventional G-banding: 8 with deletions 7q and 25 with translocations. In 29 of the patients, complex karyotypes were confirmed using multicolor fluorescence in situ hybridization (mFISH). Commercial probes (Abbot Molecular) were used for 7q22, 7q31, and 7q35, the regions most frequently deleted in myeloid malignancies. In three cases without deletions, high-resolution multicolor banding (mBAND) for chromosome 7 revealed other aberrations. Five groups of chromosomal rearrangements were established: (a) deletion 7q as a sole aberration (2 cases), (b) deletion 7q and complex karyotypes (6 cases), (c) combined translocations and deletions of 7q (17 cases), (d) combined translocation and deletion 7p (5 cases), and (e) translocation of chromosomes 7 without deletion 7p or 7q (3 cases). Deletions of all three FISH-screened regions were the most frequent, with heterogeneous breakpoints. The region 7p13.2 approximately p15.2 was most commonly deleted. Most of the deletions were cryptic, not detectable with conventional cytogenetics. Aberrations of chromosome 7 are associated with a very poor outcome; survival time in our cohort was short (median 7 months). PMID- 17284365 TI - A multicenter evaluation of comprehensive analysis of MLL translocations and fusion gene partners in acute leukemia using the MLL FusionChip device. AB - Rearrangements of the MLL gene are significant in acute leukemia. Among the most frequent translocations are t(4;11)(q21;q23) and t(9;11)(p22;q23), which give rise to the MLL-AFF1 and MLL-MLLT3 fusion genes (alias MLL-AF4 and MLL-AF9) in acute lymphoblastic and acute myeloid leukemia, respectively. Current evidence suggests that determining the MLL status of acute leukemia, including precise identification of the partner gene, is important in defining appropriate treatment. This underscores the need for accurate detection methods. A novel molecular diagnostic device, the MLL FusionChip, has been successfully used to identify MLL fusion gene translocations in acute leukemia, including the precise breakpoint location. This study evaluated the performance of the MLL FusionChip within a routine clinical environment, comprising nine centers worldwide, in the analysis of 21 control and 136 patient samples. It was shown that the assay allowed accurate detection of the MLL fusion gene, regardless of the breakpoint location, and confirmed that this multiplex approach was robust in a global multicenter trial. The MLL FusionChip was shown to be superior to other detection methods. The type of molecular information provided by MLL FusionChip gave an indication of the appropriate primers to design for disease monitoring of MLL patients following treatment. PMID- 17284366 TI - Automated detection of residual leukemic cells by consecutive immunolabeling for CD10 and fluorescence in situ hybridization for ETV6/RUNX1 rearrangement in childhood acute lymphoblastic leukemia. AB - Among the various methods available for analyzing minimal residual disease, a new procedure for the cell-based approaches using consecutive phenotypic and genotypic analysis as revealed by immunofluorescent labeling and subsequent fluorescent in situ hybridization (FISH) has been developed. We are introducing a fluorescent microscopy-based technique by which not only cellular targets and immunological marker positivity, but also the FISH pattern was identified by automated scanning. For the latter one translocation-specific FISH pattern recognition was accomplished by using an automated scanning mode for the 3D determination of valid distances between FISH signals, to define the cutoff value for the shortest green-red spot distance differentiating positive cells from negative ones. The procedure was tested with CD10(+) acute lymphoblastic leukemia cell line harboring the t(12;21)(p13;q22) resulting in the ETV6/RUNX1 rearrangement (formerly TEL/AML1), as well as peripheral blood lymphocytes of healthy individuals. Using the combined, automated method, a sensitivity of 98.67% and a specificity of 99.97% were obtained. The mean false positivity + 2 standard deviations cutoff level (0.09%) allows detection of leukemic cells with high accuracy, even a bit below the tumor load dilution of 10(-3), a value reported to be critical in clinical decision making. PMID- 17284367 TI - Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer. AB - Hypermethylation in the promoter region has been associated with a loss of gene function that may give a selective advantage to neoplastic cells. In this study, the methylation pattern of genes CDKN2A (alias p14, p14(ARF), p16, p16(INK4a)), DAPK1, CDH1, and ADAM23 was analyzed in 43 samples of head and neck tumors using methylation-specific polymerase chain reaction. In the oropharynx, there was a statistically significant association between hypermethylation of the DAPK1 gene and the occurrence of lymph node metastases, and in the larynx there was statistically significant evidence of an association between hypermethylation of the ADAM23 gene and advanced stages of the tumors. Thus, a correlation was observed between hypermethylation of the promoter region of genes DAPK1 and ADAM23 and the progression of head and neck cancer. PMID- 17284368 TI - Polymorphism of TP53 codon 72 showed no association with breast cancer in Iranian women. AB - Breast cancer is the most common female malignancy worldwide. Despite the high incidence of sporadic cases, the rate of familial breast cancer is low. The tumor suppressor gene TP53 (alias p53), located on chromosome 17, has been involved in various malignancies. Mutations in codon 72 of TP53 have been studied in breast cancer and most solid tumors. For study of polymorphisms and allele frequency, 221 female patients with sporadic breast cancer and 205 healthy blood donors as control group were recruited. DNA from peripheral blood mononuclear cells was extracted and amplified using allele-specific polymerase chain reaction. Frequency of homozygotic arginine at codon 72 was 37.6% in patients and 36.6% in controls, for homozygotic proline it was 13.1 and 19.5%, and for heterozygotic Arg/Pro it was 49.3 and 43.9%, respectively. No significant difference was found between patients and controls regarding allele frequencies. Mutation in codon 72 of TP53 gene was not associated with breast cancer in Iranian patients. PMID- 17284369 TI - Bipolar genome reductional division of human near-senescent, polyploid fibroblast cells. AB - The rise in mitotic polyploid cells in near-senescence (phase III) of human fibroblast cells has been found to contain diplochromosomes (four chromatids). For tetraploid cells, this translates into 46 pairs of sister chromosomes. It has been suggested, from the increase in numbers of such cells, that they might deviate from expected normal, single chromatid segregations in mitosis. In this study, the polyploid cells with diplochromosomes were shown to segregate by bipolar mitosis into genome-reduced cells. Sister pairs separated from each other and moved as a genomic group of two-chromatid chromosomes to the poles. A tetraploid cell thus became reduced to two diploid cells (i.e., G2-4c in G1), which in the next mitosis could either restore the previous diplochromosomal status and ploidy level or cycle as diploid mitotic cells. The polyploid cells that are programmed for genome reductional division become part of the senescent cell population. In such populations, there is depolyploidization into multinucleated cells (MNCs) that can spawn genome-reduced mitotic offspring cells. These facts are relevant to neoplasticity-associated cytopathologies such as 4n cells as intermediates in Barrett's esophagus, MNCs in human papillomavirus infections, and radiation-associated cell changes. On a cell population level, the bipolar genome reductional division is a source for genetic heterogeneity, generating a continued mixture of polyploid and genome-reduced cells. The only other known case is in the mosquito, but the phenomenon is likely more common than has been thought. PMID- 17284370 TI - Frequency and distribution of trisomy 11 in multiple myeloma patients: relation with overexpression of CCND1 and t(11;14). AB - Multiple myelomas (MM) recently have been stratified into five groups (TC1-TC5) on the basis of the presence of the recurrent IgH chromosomal translocation and cyclin D expression. Cyclin D1 is detectable in up to one third of MM patients and plays crucial role in the regulation of G1-S transition in cell cycle. To evaluate the mechanisms of cyclin D1 overexpression, fluorescence in situ hybridization analysis with specific probes for the CCND1 gene and t(11;14)(q13;q32) were performed on highly purified plasma cells from bone marrow samples of 30 MM patients at diagnosis. CCND1 gene overexpression was detected in 14/30 cases (46.6%). Patients with evidence of the t(11;14) showed strong nuclear staining for cyclin D1 (TC1 group) and 7/8 demonstrated CCND1 overexpression. The remaining 7/15 cases with increased CCND1 gene copy numbers lacked the t(11;14) and showed low to negative levels of cyclin D1 protein (TC2 group). Trisomy 11 was demonstrated in 2/8 cases carrying the t(11;14) (TC1), 6/7 overexpressing cyclin D1 without the translocation (TC2), and 4/15 negative for both alterations (TC3-TC5). According to our data, trisomy 11 does not appear to directly cause CCND1 gene overexpression because it was present in 4/15 patients without the overexpression of the CCND1 gene and in 2/8 patients carrying the t(11;14). One patient belonging to the TC2 group overexpressed cyclin D1 and lacked both trisomy and translocation, suggesting that cyclin D1 can be dysregulated by additional mechanisms. In the TC2 group, trisomy 11 may probably be considered as a recurrent polisomy of the hyperdiploid status. PMID- 17284371 TI - Cytogenetics of agnogenic myeloid metaplasia: a study of 61 patients. AB - Agnogenic myeloid metaplasia (AMM) or idiopathic myelofibrosis is a chronic myeloproliferative disorder characterized by fibrotic bone marrow, extramedullar haematopoiesis, and a leukoerythroblastic picture in circulating blood. The cytogenetic data on AMM are scanty and no recurring chromosome abnormality has been associated with the natural course of this disease. Trisomy 1q, del(13q), del(20q), and trisomy 8, appear in about two thirds of patients with demonstrable chromosome aberrations. We report on the cytogenetic analyses of 61 consecutive patients with AMM studied at diagnosis. The metaphases could not be found in 10/61 (16.4%) patients, and chromosome studies were successful in 51 patients. Twenty-one patients (41%) had an abnormal clone, whereas 30 (59%) patients had a normal karyotype. Most frequent pathological findings included trisomy 8 (either alone or within a complex karyotype) in five patients, aberrations of chromosome 12 (translocation in two, monosomy in two, and trisomy in one patient), and aberrations of chromosome 20 (interstitial deletion in two, monosomy in two, and trisomy in one patient). We also detected aberrations of chromosome 13 (translocation in two and an interstitial deletion and trisomy in one patient each) and chromosome 18 (derivative 18 in two patients and a monosomy and deletion in one patient each). Three patients exhibited complex aberrations involving several chromosomes, sometimes with a mosaicisam. A near-tetraploid karyotype was observed in a single patient. Balanced translocations [t(2;16)(q31;q24), t(5;13)(q13;q32), t(12;13)(p12;q13), and t(12;16)(q24;q24)] were present in four patients. While the series of patients studied displayed chromosomal aberrations that are frequently observed in AMM, we found some new abnormalities (balanced translocations and polyploidy) that are rarely observed in AMM. PMID- 17284372 TI - EGFR sequence variations and real-time quantitative polymerase chain reaction analysis of gene dosage in brain metastases of solid tumors. AB - Clinical response to Gefitinib (Iressa, ZD1839) has been found to be associated with somatic mutations, primarily of exons 18-21, of the epidermal growth factor receptor gene (EGFR) in non-small cell lung cancer (NSCLC). Evidence of a positive response was also reported recently on a patient with brain metastasis from NSCLC. On the other hand, amplification of EGFR appears to be associated with a poor prognosis. To determine whether EGFR mutations and amplification are involved in the tumorigenesis of brain metastases, we performed polymerase chain reaction/single-strand conformation polymorphism to examine exons 1, 2, and 7-26 of EGFR in a series of 18 brain metastases. The metastases derived from malignant melanoma (three cases), lung carcinoma (six cases), breast carcinoma (three cases), ovarian carcinoma (two cases), and one each from colon, kidney, bladder, and undifferentiated carcinoma. In addition to several sequence polymorphisms, we identified two mutations on E19 consisting of 18-base pair (bp) deletions: 2423 24440del and 2426-2443del. These mutations presented in lesions derived from kidney carcinoma and lung adenocarcinoma. By real-time quantitaive polymerase chain reaction technique, we determined the amplification/overdose status of EGFR by analyzing exons 11 and 25. Amplification (5- to 100-fold) was identified in three tumors, and overdose (low-level gene amplification corresponding to increases of 1- to 5-fold) presented in four additional metastases. These findings suggest that EGFR mutations and polymorphisms are not exclusively present in metastases derived from lung carcinoma. Accordingly, targeting of EGFR to determine molecular alterations of this gene may be useful in the management of patients with brain metastases. PMID- 17284373 TI - Transformed follicular lymphoma with concurrent t(2;3), t(8;14) and t(14;18). AB - An elderly Chinese man who had an 8-year history of follicular lymphoma presented with large B-cell lymphoma. The disease ran a rapidly fatal course with a terminal leukemic phase. Cytogenetic analysis of the transformed follicular lymphoma showed a complex karyotype of 48,Y,t(X;19)(q26;p13.3),t(2;3)(p12;q27),t(8;14)(q24.1;q32),+12,t(14;18)(q32;q21), 21. To my knowledge, this is the first reported case of simultaneous occurrence of t(2;3), t(8;14), and t(14;18) in transformed follicular lymphoma. PMID- 17284374 TI - A new cytogenetic abnormality, t(2;7)(q33;q36), in acute promyelocytic leukemia. AB - We report the case of a patient with acute promyelocytic leukemia (APL) carrying a novel chromosomal abnormality, t(2;7)(q33;q36). The 54-year-old woman was morphologically diagnosed with APL through bone marrow aspiration. The proportion of blast cells in bone marrow was 78%, including cells displaying Auer rods and faggot cells. Chromosomal analysis revealed the karyotype 46,XX,t(2;7)(q33;q36)[17]/46,XX[3]. The t(15;17) was not detected with conventional cytogenetic analysis. However, reverse transcriptase-polymerase chain reaction revealed the presence of a PML/RARA fusion gene. Cells displaying t(2;7)(q33;q36) disappeared after complete remission was achieved, using induction chemotherapy. Although several additional chromosomal abnormalities have been reported, this t(2;7)(q33;q36) without the classic t(15;17) represents a novel chromosomal abnormality associated with APL. PMID- 17284375 TI - Cytogenetic findings in pediatric renal cell carcinoma. AB - Adenocarcinomas of the kidney are rare childhood tumors. Only 30 cases with chromosomal abnormalities have been reported, and neither their karyotypic characteristics nor the molecular mechanisms behind their pathogenesis are clear, except for a special group of papillary tumors characterized by X-chromosome abnormalities. We have cytogenetically analyzed short-term cultured cells from two pediatric renal carcinomas, one papillary, and one chromophobe renal cell carcinoma, revealing the following karyotypes: 58-60,XX,-X,-1,+7,-8,-9,-11,-14, 15,+17,-18,-19,-21,-22 and 36,X,-X,-1,-2,-5,-6,-9,-10,-13,-17, 21/37,idem,+r/36,idem,-14,+1-2r, respectively. The findings indicate that subsets of pediatric renal cell carcinoma show karyotypes that are similar to their adult counterparts. PMID- 17284376 TI - Translocation (10;21)(q21;q22) in myelodysplastic syndrome. PMID- 17284377 TI - Presence of t(1;14)(p13;p11.2) in Philadelphia chromosome-negative cells in a patient with chronic myeloid leukemia. PMID- 17284379 TI - Interstitial implant alone or in combination with external beam radiation therapy for intermediate-risk prostate cancer: a survey of practice patterns in the United States. AB - PURPOSE: This study is aimed at understanding and defining the current patterns of care with respect to prostate brachytherapy for patients with intermediate risk localized disease in the combined academic and community setting. METHODS AND MATERIALS: A nomogram-based survey was developed at the Seattle Prostate Institute defining the accepted criteria for intermediate-risk prostate cancer. Patients were defined as having intermediate-risk prostate cancer if they met one of the following criteria: prostate-specific antigen (PSA) >10 ng/dL, Gleason score (GS) > or = 7, or cT2b or cT2c disease. Additional potential predictive factors including perineural invasion (PNI), GS 3+4 vs. 4+3, and high-volume disease were included. RESULTS: In the absence of PNI, all of those surveyed would perform monotherapy for intermediate-risk patients, GS 7 (3+4) or PSA 10 20, with cT1c and <30% cores +. Up to 80% would perform monotherapy for patients with cT1c, GS 7 (4+3), and <30% cores +. Eighty to 90% of physicians would perform an implant alone with cT2a and either a PSA of 10-20 or GS of 7 (3+4) and <30% cores +. Fifty to 60% of those surveyed stated that they would treat a patient with cT2b disease, GS 7 (3+4), or PSA 11-20, with less than two-thirds of the biopsy cores positive in the absence of PNI. CONCLUSIONS: This Patterns of Care (POC) study reveals that certain subsets of intermediate-risk localized prostate cancer patients are considered appropriate candidates for an interstitial implant alone. PMID- 17284380 TI - Initial analysis of Pro-Qura: a multi-institutional database of prostate brachytherapy dosimetry. AB - PURPOSE: The study aimed to analyze the Pro-Qura database in terms of patient implant sequence number for each institution to determine evidence for a dosimetric learning curve. METHODS AND MATERIALS: In the Pro-Qura database, 2833 of a total of 4614 postplans from 57 brachytherapists were analyzed for evidence of a dosimetric learning curve. The median time between implant and postimplant CT scan was 30 days. I-125 was used in 2123 patients (1687 monotherapy and 536 boost) and Pd-103 in 710 patients (367 monotherapy and 343 boost). Preimplant prostate volume was 35.3 and 32.9 cm3 in the I-125 and Pd-103 cohorts, respectively. The mean I-125 seed activity was 0.32 and 0.26 mCi for monotherapy and boost, whereas for Pd-103 the mean seed activity was 1.59 and 1.27 mCi, respectively. Postimplant dosimetry was performed in a standardized fashion by overlaying the preimplant ultrasound and the postimplant CT scan. Criteria for implant adequacy included a D90 >90% and a V100 >80% for both isotopes. An adequate V150 was defined as <60% for I-125 and <75% for Pd-103. RESULTS: The mean V100 and D90 were 88.9% and 101.9% of prescription dose, respectively. When analyzed in terms of patient sequence number for each institution, the mean V100 for the first 10 patients was 87.4% and increased to 88.6% for patients 11-20 (p = 0.036). Similarly, the mean D90 for the first 10 patients was 98.9%, whereas for the second cohort of 10 patients the mean D90 increased to 102.2% (p = 0.001). In terms of mean V100 and D90, there was minimal further change for subsequent 10 patient institutional groupings of patient sequence numbers. For the first 10 cases, 27.2% were deemed "too cool" (V100 <80% and/or D90 <90%). Approximately 16% of all implants were deemed "too hot" (D90 >140% or V150 >60% for I-125 or >75% for Pd-103). CONCLUSIONS: Although a learning curve exists for prostate brachytherapy, high-quality brachytherapy is achievable in approximately 75-80% of patients treated at community centers. PMID- 17284382 TI - Assessment of postbrachytherapy sexual function: a comparison of the IIEF-5 and the MSEFS. AB - PURPOSE: This study is to compare the Mount Sinai Erectile Function Score (MSEFS), our brachytherapy program's physician-assigned scale, with patients' independently completed International Index of Erectile Function-5 (IIEF-5). METHODS AND MATERIALS: A total of 1202 patients with T1-T3 prostate cancer were treated with ultrasound-guided radioactive seed implantation +/- EBRT with at least one visit where both MSEFS and IIEF-5 were completed. Spearman rho correlations were performed. RESULTS: The MSEFS significantly correlated with the total IIEF-5 scores on all comparisons. The coefficient was 0.65 for comparisons at initial consultation and 0.76 for all visits. The correlations remained strong, averaging to 0.76 for visits 1 through 10. CONCLUSIONS: In assessing erectile dysfunction after radiation, the MSEFS correlates well with, but cannot be replaced by, the IIEF-5, which is weighted toward one's degree of sexual desire. More insight into patients' erectile function after brachytherapy may be gotten if the IIEF-15 is used instead of the IIEF-5 with our MSEFS. PMID- 17284381 TI - Biochemical disease-free survival rates following definitive low-dose-rate prostate brachytherapy with dose escalation to biologic target volumes identified with SPECT/CT capromab pendetide. AB - PURPOSE: To report biochemical disease-free survival (bDFS) after conformal brachytherapy with dose escalation to biological target volumes (BTVs) identified by Capromab Pendetide with single photon emission computed tomography and computed tomography image fusion (SPECT/CT). METHODS AND MATERIALS: Two hundred thirty-nine (T1c-T3b NxM0) consecutive patients were evaluated by SPECT/CT before treatment. Intraprostatic SPECT/CT BTVs were identified and targeted for 150% dose escalation during brachytherapy seed implant (SI). Patients received either SI alone (n = 150) or external beam radiation therapy (EBRT) plus SI boost (EBRT+SI) (n = 89), with (n = 50) and without (n = 189) neoadjuvant hormone ablation therapy. Risk factors (RF) (prostate-specific antigen [PSA] >10 ng/mL, Stage > or = T2b, and Gleason grade > or = 7) defined risk group (RG) categories [none, 1, and > or = 2 RF define low, intermediate, and high RG] for bDFS calculations using four failure criteria: American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition, PSA >1.0 ng/mL (PSA >1), PSA >0.5 ng/mL after nadir (PSA >0.5), and PSA nadir+2 ng/mL rise in PSA clinical nadir (CN+2). Median followup was 47.2 months (range, 24.8-96.1). RESULTS: Seven year actuarial bDFS rates were 88.0%, 82.1%, 80.4%, and 79.9% using the ASTRO, PSA >1, PSA >0.5, and CN+2 failure criteria, respectively. ASTRO-defined bDFS rates were 96.0%, 87.0%, and 72.5% for low, intermediate, and high RG's. CONCLUSION: The data presented here demonstrate the feasibility of performing SPECT/CT BTV dose escalation in a mature series. PMID- 17284384 TI - Is seminal vesicle implantation with permanent sources possible? A dose-volume histogram analysis in patients undergoing combined 103Pd implantation and external beam radiation for T3c prostate cancer. AB - PURPOSE: Combined brachytherapy and external beam radiation therapy (EBRT) of the prostate and seminal vesicles (SVs) is evolving as a successful treatment option for high-risk prostate cancer. Dose-volume histogram (DVH) analysis of the SV was performed in patients with biopsy-positive SV who received implantation of the SV and prostate. METHODS AND MATERIALS: Fifteen consecutive patients with high-risk features (prostate-specific antigen [PSA] > or =10 ng/mL, Gleason score > or = 7, or clinical stage > or = T2b) and a positive SV biopsy were treated with a 103Pd implant of the prostate and SV followed by 45Gy of EBRT. DVHs were generated for the prostate and total SV volume (SVT). In addition, the SV was divided into 3-mm thick volumes identified as SV1, SV2, SV3, SV4, SV5, and SV6 starting from the junction of the prostate and SV and extending distally. Delivered dose was defined as the D90 (dose delivered to 90% of the organ on DVH). RESULTS: The median number of seeds implanted into the prostate and the SVT was 59 (41-94) and 9 (4-21), respectively. The median D90 values for the prostate, SVT, SV1, SV2, SV3, SV4, SV5, and SV6 were 103.2 (87.4-137.1), 46.2 (4.0-69.4), 76.0 (31.2-147), 63.4 (25.1-145.9), 49.7 (15.3-118), 27.4 (9.3-135.1), 14.2 (2.3-100.3), and 3.9 (0-61.5) Gy, respectively. CONCLUSIONS: Implantation of the SV using a real-time intraoperative approach is technically feasible and results in higher doses to the SV than has been reported with implantation of the prostate alone. Although dose distribution in the SV can be variable and unpredictable, these doses, in combination with 45 Gy of EBRT, may be adequate to control disease spread in these organs. PMID- 17284385 TI - Improvements in prostate brachytherapy dosimetry due to seed stranding. AB - PURPOSE: Prostate brachytherapy with suture embedded seeds has emerged as a popular technique to reduce seed migration and to improve dosimetry. Various trials have shown improved dosimetry with seed fixity, whereas others have shown no benefit and possible detriment to suture embedded seeds. In order to contribute to the understanding of whether seed stranding improves dosimetry, we present retrospective data from our institution. METHODS AND MATERIALS: We analyzed 80 patients treated between April 29, 2001 and June 19, 2006, receiving I-125 monotherapy for prostate cancer. Brachytherapy patients at the University of California, Los Angeles (UCLA) were initially treated using a transperineal approach with loose seeds. Subsequent to October 26, 2002, all patients were implanted using suture embedded seeds. Dosimetric quantifiers were calculated based on a CT obtained 1-month postimplantation. RESULTS: Dosimetry of patients treated with stranded seeds showed significant improvement. Specifically, the V100 (volume of the prostate receiving 100% of the prescribed dose) improved from 88% to 92% (p<0.05), and the D90 (maximum dose received by 90% of the prostate) improved from 143 to 155 Gy (p<0.05). CONCLUSIONS: At UCLA, the use of suture embedded seeds resulted in a significant improvement in our dosimetric quantifiers. Based upon other published studies, this improvement in dosimetry may translate into improved patient outcomes. PMID- 17284383 TI - American Brachytherapy Society recommends no change for prostate permanent implant dose prescriptions using iodine-125 or palladium-103. AB - PURPOSE: In 2004, the American Association of Physicists in Medicine (AAPM) issued a report outlining recommended 125I and 103Pd datasets for consistency in calculating brachytherapy dose distributions. In 2005, to aid evaluating the clinical impact of implementing these datasets, the AAPM assessed the historical dependence of how prescribed doses differed from administered doses for 125I and 103Pd for permanent implantation of the prostate. Consequently, the American Brachytherapy Society (ABS) considered the nature of these changes towards issuing recommended dose prescriptions for 125I and 103Pd interstitial brachytherapy implants for monotherapy and standard boosts. METHODS AND MATERIALS: An investigation was performed of the 2005 AAPM analysis to determine changes in administered dose while affixing prescribed dose using 2004 AAPM 125I and 103Pd brachytherapy dosimetry datasets for prostate implants. For 125I and 103Pd, administered dose would change by +1.4% and +4.2%, respectively. The biological and societal impact of changing prescribed dose was considered. RESULTS: Based on the need for clinical constancy and in recognition of overall uncertainties, the ABS recommends immediate implementation of the 2004 AAPM consensus brachytherapy dosimetry datasets and no changes to 125I and 103Pd dose prescriptions at this time. CONCLUSIONS: Radiation oncologists should continue to prescribe monotherapy doses of 145 Gy and 125 Gy for 125I and 103Pd, respectively, and standard boost doses of 100-110 Gy and 90-100 Gy for 125I and 103Pd, respectively. PMID- 17284386 TI - Dosimetry of anal radiation in high-dose-rate brachytherapy for prostate cancer. AB - PURPOSE: The objective of this study is to determine the radiation dose to the anus during brachytherapy using high-dose-rate Ir-192 sources. METHODS AND MATERIALS: Thermoluminescence dosimeters were used for measuring the dose to the distal part of the anus in 10 patients, and in a prostate phantom to measure the radiation dose during the transport of the radiation source. RESULTS: The measured dose to the anus in vivo was on average 0.85 Gy (range, 0.48-1.37 Gy) per treatment. The transport dose using 15 and 19 needles in the prostate phantom was 0.07 and 0.08 Gy, respectively. CONCLUSIONS: The dose delivered to the anus using high-dose-rate brachytherapy with Ir-192 sources is quite low. There is a contribution to the anal radiation dose during the transport of the Ir-192 source into the needles. However, in clinical practice when using 15-20 needles, the dose from transporting the Ir-192 source can be ignored. PMID- 17284387 TI - Adjuvant high-dose-rate and low-dose-rate brachytherapy with external beam radiation in soft tissue sarcoma: a comparison of outcomes. AB - PURPOSE: To compare outcomes of patients treated with low-dose-rate (LDR) adjuvant brachytherapy (BT) + external beam radiation therapy (EBRT) vs. high dose-rate (HDR) adjuvant BT + EBRT. METHODS AND MATERIALS: Thirty-seven patients with soft tissue sarcoma (STS) were treated with pre- or postoperative external beam irradiation and postoperative LDR or HDR BT. RESULTS: There was no significant difference in the 2-year local control rates (90% with LDR boost vs. 94% for HDR). The rate of National Cancer Institute (NCI) grades 2-4 wound healing complications was 40% in the LDR group vs. 18% in the HDR group (p = 0.14). On univariate analysis, only suboptimal geometry of the implant predicted for increasing complication rate in the LDR group. In the HDR group, BT dose per fraction, total BT dose, and total biologically equivalent dose (BED3) radiation dose were significant. CONCLUSIONS: HDR and LDR boost BT results in acceptable local control for STS. There is a suggestion that HDR may have lower incidence of severe (grade > or = 3) acute toxicity than LDR. PMID- 17284388 TI - Severe toxicity after permanent radioactive seed implantation for mediastinal carcinoid tumors. AB - PURPOSE: Permanent implantation of 125I seeds may be used when uninvolved surgical margins are unobtainable or close. Two cases of mediastinal carcinoid tumors with prior chemoradiation had tumors adherent to esophageal muscularis. Both underwent intraoperative permanent seed implantation and developed esophageal fistulas requiring surgical correction. METHODS AND MATERIALS: Custom permanent 125I seed mesh implants were fashioned intraoperatively in a geometrically coherent pattern. The implants were directly sutured to the partially resected esophageal wall. The postimplant CT scans were fused with the postfistula scans to provide dosimetric information at the fistula site. Doses were calculated from time of insertion to time of fistula formation. Neither patient showed evidence of disease recurrence at the time of fistula repair. RESULTS: Patient 1 developed an esophageal-pleural fistula 83 days after seed implantation. Patient 2 developed a broncho-pleural fistula 300 days after seed implantation. CONCLUSIONS: These cases demonstrated that implantation in the setting of extensive subcarinal space dissection and partial esophageal wall resection could cause fistula formation and the need for additional surgery. The high mucosal dose, despite the relatively low activity implant, was due to lack of geometric sparing of the mucosa. We recommend that extensive subcarinal space dissection be considered a contraindication to permanent seed implantation. PMID- 17284389 TI - [Service quality assurance by death analysis during the 2004 cholera outbreak in Douala]. AB - Morbidity and mortality conferences (MMC) are used today in most medical departments as a tool for quality assurance as well as an educational tool. We introduced MMC with regard to cholera lethality during the 2004 cholera outbreak in Douala. The Delegation of Public Health (DPH) in Douala, coordinating body for the combat against the epidemic, decided to open cholera treatment units (CTU) in fourteen hospitals, equally distributed over the town. The CTUs' personnel was retrained on diagnostic and treatment protocols, procedures to follow and on management tools. To assure the quality of services, a provincial supervision team was constituted for the close follow-up of the CTUs. The supervision team had two main tasks, i.e. on-the-job training of the personnel involved in the care of cholera patients and systematic meetings whenever a cholera death occurred during hospital stay in order to analyse the reasons behind the death. We communicate our experience with these systematic meetings inspired by the MMC and aiming at the analysis of cholera deaths in the CTUs. Immediately after a cholera death in one of the CTUs, a meeting was organised by a member of the supervision team, assisted by the entire CTU team. During the meeting, the patient's file was re-examined as were the decisions token, the actions undertaken by the personnel, and the difficulties met. Alternative decisions and actions were discussed and conclusions based on the lessons learned formulated. Of all meetings minutes were kept. A monthly provincial meeting, joining all CTU teams, was organized for discussion of the minutes, exchange of experiences, and, eventually, adapting of protocols, procedures, and management tools. Five thousand and twenty cholera patients were notified during an 8-months-period (January-August 2004), 69 (1.4%) of the patients died, amongst them 8 before the declaration of the epidemic and 4 before hospital admission. Eleven CTUs out of a total of 14 organised 15 meetings concerning 39 (68%) of the 57 hospital based cholera deaths. Eight to eighteen CTU team members participated (with 2-5 physicians according to the CTU) and the meetings lasted between 1 and 2 hours. The meetings proceeded in a systematic way: after controlling for the presence of all CTU team members concerned, the patient's file was read together, team members were asked to elucidate what did not figure in the file, everybody was asked for commentaries and suggestions, the supervisor made a synthesis of the discussion, and, finally, conclusions and recommendations were formulated. The minutes of the meeting were sent to the DPH. The conclusions and recommendations aimed at the reception of the patients and his admission circuit, the diagnostic procedures, therapy, the case definition, the evaluation of the severity of the patient's status at the moment of admission, the surveillance during evolution of the patient, the respect of the therapeutical protocols, and the management of the CTU. In spite of the organisational, psychological, and socio-cultural difficulties, the meetings went off apparently without major reservations in the minds of the participants. These meetings analysing the reasons behind a case of cholera dying in a CTU gave the opportunity to discuss performance, to identify problems, and to search together for solutions. They were thought of as a tool for improving the quality of the service. Looking at the low over-all lethality rate during this major epidemic they seemed to have, at least partially succeeded. PMID- 17284391 TI - [Serum cholinesterase activity as a biomarker of insecticide exposure in Moroccan farmers]. AB - This study sought to assess chronic insecticide exposure of farmers in the Moroccan province of Settat. The biomarker we used for this exposure was serum cholinesterase activity, which decreases in response to insecticides. The study took serum samples from 325 people, with an average age of 29.8 +/- 19.6 years, 51.7% women and 48.3% men. All came from 3 villages around the city of Settat. The subjects, all of whom consented to participate, received a complete clinical examination and provided information on their medical history, occupation and insecticide exposure. Cholinesterase activity was measured by kinetic spectrophotometry. The average value for the overall population was 4059.9 +/- 658.3 U/l, 4008.6 +/- 717.5 U/L for the 168 women and 4114.9 +/- 585.7 U/L for the 157 men. This difference was not significant. Reduced cholinesterase activity was not observed in any subjects, probably because of the limited use of insecticides in this region. The use of insecticides in farming environments must nonetheless be regularly assessed and farmers must be trained in their safe use. PMID- 17284390 TI - [Vaccination status of children with sickle cell disease in Ouagadougou (Burkina Faso)]. AB - Because of the importance of preventive activities in fighting sickle cell disease, we sought to assess the vaccination status of children with this disease in Burkina-Faso. This cross-sectional study used a questionnaire to collect information from outpatients of the pediatric department of the Yalgado Ouedraogo hospital center and of Saint Camille medical center, also in Ouagadougou, from October 2005 through March 2006. The study included 122 children, 52.5% of whom had an SC phenotype. Coverage for vaccinations included in the WHO expanded vaccination programme was 97.5%. For other specific vaccines, coverage varied from 5.7% for the anti-Haemophilus influenzae vaccine to 65.8% for the 23 pneumococci included in pneumo23. The major reasons for non-vaccination were ignorance and the prohibitive cost of these vaccines for the families who knew about them. These results suggest the need for a national program against sickle cell disease, which should enable treatment centers to include in their preventive activities a specific vaccination program. Only in this way can we reduce the mortality rates among those younger than 5 years by 40% by 2015, the goal of the International Organization against sickle cell disease, to which Burkina-Faso belongs. PMID- 17284392 TI - [Therapeutic maintenance level of methotrexate in rheumatoid arthritis]. AB - OBJECTIVES: To determine the probability of drug continuation, the reasons for discontinuation of methotrexate (MTX), and risk factors of treatment termination in rheumatoid arthritis. MATERIALS AND METHODS: Retrospective cohort study of a 100 case follow-up between 1983 and 2003, all treated with MTX. Factors associated with toxicity, and efficacy of MTX were studied. Logistic regression was used to study the relation between baseline variables and various dependent factors. RESULTS: Eighty three women and seventeen men were included in this study. The mean age at commencement of MTX was 45+/-13.7 (18-81) years. The mean duration of disease was 9.5+/-8.7 (0.25-40) years. The mean weekly dose of MTX was 9.8+/-3.4 mg/week. The therapeutic maintenance level of MTX was 76% at one year, 63% at 2 years and 45% at 5 years. The median of treatment duration was 10 (0. 5-40) months. Reasons for patients stopping MTX were: Adverse effects (15), lack of effect (1), non medical reasons (14) essentially because of financial difficulties. Baseline white blood cell counts >9 giga/mm3 (RR: 3.17) [95 %:1.03 9.74] (p=0.04) and baseline serum creatinine level >72 micromol/L (RR: 8.6) [95 %:1.04-71.17] (p=0.04) were associated with an increased risk of treatment termination. CONCLUSION: The continuation rate of methotrexate in our study was good, despite the poor compliance with the treatment due to financial difficulties. PMID- 17284393 TI - [Surgery and HIV in Bangui (Central African Republic)]. AB - Routine presurgical testing for HIV is a matter of controversy. The risk of intraoperative contamination and postoperative complications, especially opportunistic infections, justifies this practice. OBJECTIVE: To assess the real prevalence of HIV in surgical departments in the Central African Republic (CAR) and, more precisely, its impact on surgery patients and staff, as well as measures of prevention. METHOD: This exploratory study took place from September 1st, 2001, through October 31st, 2002, in the general surgery departments of Amitie Hospital in Bangui (CAR). The patients tested were randomly selected after surgery, and their serum tested at the hospital laboratory by ELISA methods. RESULTS: The sample included 207 patients, 58.9% of whom were women. Their average age was 32 years (range: 15-72 years. Surgery was elective for 111 patients (53.6%) (for example, for uncomplicated hernias or gynecological problems) and performed on an emergency basis for 96 (46.4%). The latter included appendectomies (20.3%), laparotomies (14%), and strangulated hernias (12%). Overall, 49 patients (23.6%) were HIV-positive. Wound infection (51 cases) and septic shock (4 cases) were significantly more frequent in HIV-positive than in HIV-negative patients, as was mortality. COMMENTS: Patients with HIV developed postoperative complications, but so did HIV-negative patients. Practitioners should stress specific care for HIV-positive patients without insisting on discriminatory testing. Especially important are sterilization of medical and surgical materials, and universal precautions and asepsis, including personal prevention measures for healthcare staff. PMID- 17284394 TI - [Nonpalpable breast lesions: correlation of the BI-RADS classification and histologic findings]. AB - Diagnosis of nonpalpable breast lesions too often requires a breast biopsy or tumorectomy. OBJECTIVE: To validate the American College of Radiology (ACR) classification and lexicon using a standardized description to improve the uniformity of management of abnormal mammographic lesions and reduce the number of unnecessary tumorectomies. MATERIAL AND METHODS: This prospective study was conducted in Libreville Hospital Center over a 4-year period and compared the histologic results of 150 nonpalpable masses identified by mammography and their ACR classification to assess the correlation between the radiographic and histologic findings. RESULTS: There were 90 cases (60%) of ACR2 lesions, 28 cases (18%) of ACR3, 6 cases (4%) of ACR4 and 26 cases (17%) of ACR5 lesions. Histologic results showed that 3% of the ACR2 lesions were malignant, 11% of the ACR3, 67% of the ACR4 and 92% of the ACR5 lesions. CONCLUSION: The correlations showed that the ACR classification was highly reliable for ACR2 and ACR5 lesions and makes it possible to optimize their treatment. ACR3 and ACR4 lesions must be watched carefully. PMID- 17284395 TI - [Preterm births at Brazzaville University Hospital]. AB - The objectives of our study were to assess the frequency, causes and outcomes of preterm births in Brazzaville University Hospital and to improve our obstetric and pediatric management. We retrospectively studied all births during 1994: 5109 in all. We collected information about the circumstances of preterm birth and all available information about its causes, mode of delivery, and immediate 24-h outcome. There were 852 preterm births (16.7% of all births). Mothers aged 14-20 years accounted for 27% of these births, while those 35 years or older accounted for only 9%. The 24-h survival rate was 73.7% (n=628). Those born at a gestational age of 28-30 weeks accounted for 40.7% of the deaths. The principal causes in order of frequency were: premature rupture of membranes (48%, caused by infection in 68% of cases), complications of high blood pressure (23.9%, including eclampsia, abruptio placentae and HELLP syndrome), twin pregnancies (14%), and previa placenta and hemorrhage (7%). The average time until the baby's transfer to neonatal intensive care was 12 hours, often because of an absence of beds. The principal causes of such transfer were: neonatal infection (48%), respiratory distress (27%) and gestational age less than 33 weeks (22%). Prognosis for preterm births is better at Brazzaville University Hospital at and after 33 weeks; extreme prudence is required before this term, especially for cesarean deliveries. PMID- 17284397 TI - [Risk factors for eclampsia in Libreville (Gabon): a case-control study]. AB - OBJECTIVES: To determine the current prevalence of eclampsia in our department, identify its risk factors and assess the prognosis of mother and child. MATERIAL AND METHODS: This retrospective case-control study took place from January 1, 2004, through December 31, 2005, in the gynecology-obstetrics and intensive care departments of the Libreville Hospital Center. Every case of eclampsia was compared with three control patients. We collected social, demographic and clinical variables and compared them between the two groups. Univariate analysis was conducted with Epi Info 6.0. The odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for each variable and compared with the Chi 2 test (significance defined as a p value less than 0.05). RESULTS: The prevalence of eclampsia was 0.5%. The principal risk factors were: mother aged younger than 19 years (OR=3.38; CI= 1.77-6.47), nulliparity (2.21; 1.22-4.02) and one or no prenatal consultations (19.23; 6.45-61.40). Severe high blood pressure (>160/110 mmHg) was found in 52% of cases. There were 14 maternal deaths (21%) in the case group and none among the controls. CONCLUSION: Improvement in the quality and quantity of prenatal care should help reduce the incidence of eclampsia. PMID- 17284396 TI - [Causation and treatment of infectious leucorrhoea at the Cocody University Hospital (Abidjan, Cote d'Ivoire)]. AB - OBJECTIVES: to determine the frequency of different bacteria causing infectious leucorrhoea and to calculate the percentage of cures after standard treatment. PATIENTS AND METHODS: This 7-month prospective descriptive study took place from October 2003 through April 2004 in the gynaecology department of Cocody University Hospital and in the department of sexually-transmitted infections of the Pasteur Institute of Cote d'Ivoire. After identification of the organism causing each case of leucorrhoea, we prescribed treatment according to a standard protocol. Vaginal samples were taken after treatment and tested to assess its success. RESULTS: The most frequent bacteria discovered, in descending order, were: Gardnerella vaginalis (47%), Candida albicans (29.4%), Chlamydia trachomatis (13.7%), Trichomonas vaginalis (6.9%), and Neisseria gonorrhoeae (2.9%). The overall cure rate was 87%. Treatment failure was most common for C. trachomatis (8 of 14 cases, 57.1%), N. gonorrhoeae (1 of 3 cases) and T. vaginalis (2 of 7 cases, 28.6%). Treatment was 100% effective for G. vaginalis and C. albicans. CONCLUSION: The fight against sexually-transmitted infections should be intensified, and patients and physicians cautioned about use of doubtful generic drugs. PMID- 17284398 TI - Predictive risk factors for early mortality in operative treatment for chronic ischemic mitral insufficiency. AB - BACKGROUND: The combination of coronary artery bypass grafting and mitral valve surgeries is closely associated with high in-hospital mortality and morbidity. In this study, we sought to analyze the factors that influence early mortality in 68 patients undergoing coronary artery bypass grafting + mitral valve surgery due to ischemic mitral insufficiency. METHODS: Of 1183 patients undergoing coronary bypass surgery between April 2002 and June 2006, 68 patients (42 male and 26 female) 42 to 78 years of age (mean +/- SD, 59.3 +/- 9.1) underwent mitral valve surgery accompanying coronary bypass surgery (survival, n = 59; mortality, n = 9). The cases were analyzed regarding the demographic, preoperative, and perioperative risk factors that influence mortality. RESULTS: The early mortality rate was found to be 13.2% (9/68) in patients with ischemic mitral regurgitation undergoing simultaneous coronary bypass and mitral valve surgeries. New York Heart Association class > or =3, left ventricle end-systolic volume, left ventricle end-systolic diameter, cardiopulmonary perfusion time, preoperative unstable angina pectoris, intra-aortic balloon application, and age >65 years were determined to be statistically significant risk factors that influence early in-hospital mortality.Conclusion. Surgery, despite having a high mortality risk in patients with ischemic mitral insufficiency, is considered to be a treatment measure that generally improves the quality of life and prolongs life. PMID- 17284399 TI - Computed tomography angiography is an excellent tool for the diagnosis of congenital coronary artery anomalies: a report of 2 cases. AB - Congenital coronary artery anomalies are sporadically discovered in patients undergoing coronary angiography and in autopsy series. Although most anomalies are clinically insignificant, some may become causes of cardiovascular morbidities and mortality. Diagnosis is commonly made with conventional coronary artery angiography. The current development of modern cardiac computed tomography allows less invasive imaging of the coronary arteries and might provide additional anatomical and morphological information. Herein, we report our experience with computed tomography coronary angiography, describing 2 clinical cases of patients with symptomatic congenital coronary artery anomalies requiring cardiac surgery. PMID- 17284400 TI - When to use social information: the advantage of large group size in individual decision making. AB - Correct decision making is crucial for animals to maximize foraging success and minimize predation risk. Group-living animals can make such decisions by using their own personal information or by pooling information with other group members (i.e. social information). Here, we investigate how individuals might best balance their use of personal and social information. We use a simple modelling approach in which individual decisions based upon social information are more likely to be correct when more individuals are involved and their personal information is more accurate. Our model predicts that when the personal information of group members is poor (accurate less than half the time), individuals should avoid pooling information. In contrast, when personal information is reliable (accurate at least half the time), individuals should use personal information less often and social information more often, and this effect should grow stronger in larger groups. One implication of this pattern is that social information allows less well-informed members of large groups to reach a correct decision with the same probability as more well-informed members of small groups. Thus, animals in larger groups may be able to minimize the costs of collecting personal information without impairing their ability to make correct decisions. PMID- 17284402 TI - Like mother, like daughter: inheritance of nest-site location in snakes. AB - A trait can be passed from parents to offspring even if it has no genetic basis. For example, if daughters return to reproduce at the same sites where they were hatched themselves, nest-site location is consistent within matrilineages. Most cases of natal homing (nest-site philopatry) across generations have been inferred from molecular evidence rather than directly demonstrated, and involve species with low dispersal abilities. However, some animals disperse long distances but then return to their own place of birth to reproduce, based on cues imprinted early in their own development. Our field studies on tropical natricine snakes (Tropidonophis mairii, Colubridae) show that when they are ready to nest, females return to the sites where their mothers were captured pre-nesting, and where they themselves were released as hatchlings. PMID- 17284403 TI - Exceptional preservation of nerve and muscle tissues in Late Devonian placoderm fish and their evolutionary implications. AB - In this paper, we show exceptional three-dimensionally preserved fossilized muscle tissues in 380-384 Myr old placoderm fish (Late Devonian), offering new morphological evidence supporting the hypothesis that placoderms are the sister group to all other gnathostomes. We describe the oldest soft tissue discovered in gnathostomes, which includes striated muscle fibres, circulatory and nerve tissues, preserved as phosphatized structures precipitated by microbial infilling of small, protected areas under the headshield of the arthrodire, Eastmanosteus calliaspis. Muscle impressions have also been found in the ptyctodontid, Austroptyctodus gardineri. The specimens display primitive vertebrate muscle structures; in particular, shallow W-shaped muscle blocks such as those observed in lampreys. New information from fossilized soft tissues thus elucidates the affinities of the placoderms and provides new insights into the evolution and radiation of gnathostomes. PMID- 17284401 TI - Phylogenetic relationships and divergence times of Charadriiformes genera: multigene evidence for the Cretaceous origin of at least 14 clades of shorebirds. AB - Comparative study of character evolution in the shorebirds is presently limited because the phylogenetic placement of some enigmatic genera remains unclear. We therefore used Bayesian methods to obtain a well-supported phylogeny of 90 recognized genera using 5 kb of mitochondrial and nuclear sequences. The tree comprised three major clades: Lari (gulls, auks and allies plus buttonquails) as sister to Scolopaci (sandpipers, jacanas and allies), and in turn sister to Charadrii (plovers, oystercatchers and allies), as in previous molecular studies. Plovers and noddies were not recovered as monophyletic assemblages, and the Egyptian plover Pluvianus is apparently not a plover. Molecular dating using multiple fossil constraints suggests that the three suborders originated in the late Cretaceous between 79 and 102 Mya, and at least 14 lineages of modern shorebirds survived the mass extinction at the K/T boundary. Previous difficulties in determining the phylogenetic relationships of enigmatic taxa reflect the fact that they are well-differentiated relicts of old, genus-poor lineages. We refrain from suggesting systematic revisions for shorebirds at this time because gene trees may fail to recover the species tree when long branches are connected to deep, shorter branches, as is the case for some of the enigmatic taxa. PMID- 17284404 TI - Parallel tool industries in New Caledonian crows. AB - Individual specialization in the use of foraging tools occurs in hunter-gatherer societies but is absent in non-human primate tool use. 'Parallel tool industries' in hunter-gatherers are mainly based on strict sexual division of labour that is highly reliant on social conformity. Here, we show that 12 individuals in a population of New Caledonian crows on Mare Island had strong preferences for either stick tools or pandanus tools. Eight of the 12 crows had exclusive preferences. The individual specialization that we found is probably associated with different foraging niches. However, in spite of sexual size dimorphism there was no significant association between the sex of crows and their tool preferences. Our findings demonstrate that highly organized, strict sexual division of labour is not a necessary prerequisite for the evolution of parallel tool industries. PMID- 17284405 TI - Using ghost lineages to identify diversification events in the fossil record. AB - Observed rises in taxic diversity could reflect bias of the fossil record or a genuine diversification. Here we outline a new method that attempts to differentiate between these two possible explanations. The method is based on the calculations of average ghost lineage duration through successive intervals of time. Biases due to variation in preservational conditions affect taxa independently from their position in the tree of life. A genuine radiation event will affect some parts of the tree of life more than others. During periods of rapid diversification, there will be a high proportion of new taxa showing short ghost lineages and therefore the average ghost lineage duration will drop as diversity rises, allowing us to distinguish such events from preservational bias during which ghost lineage duration remains unchanged. We test the method on Aptian-Maastrichtian (Cretaceous) ray-finned fish diversity. The result shows that a peak of diversity in the Cenomanian is associated with a drop in average ghost lineage duration, indicating that a genuine biological radiation occurred at that time. PMID- 17284406 TI - Tyrannosaur ageing. AB - Rate of ageing in tyrannosaurs was calculated from parameters of Weibull functions fitted to survival curves based on the estimated ages at death of fossilized remains. Although tyrannosaurs are more closely related to birds than to mammals, they apparently aged at rates similar to mammals of comparable size. Rate of growth in body mass of tyrannosaurs was similar to that of large mammals, and their rates of ageing were consistent with the estimated extrinsic mortality, which is strongly correlated with the rate of ageing across birds and mammals. Thus, tyrannosaurs appear to have had life histories resembling present-day large terrestrial mammals. Rate of ageing in warm-blooded vertebrates appears to be adjusted in response to extrinsic mortality and potential lifespan, independently of both physiological and developmental rates. However, individuals in species with the slowest rates of ageing suffer the highest proportion of ageing-related mortality, hence potentially strong selection to further postpone senescence. Thus, the longest observed lifespans in birds, tyrannosaurs and mammals might be close to the maximum possible. PMID- 17284407 TI - Experimental simulations about the effects of overexploitation and habitat fragmentation on populations facing environmental warming. AB - Populations of many species are dramatically declining worldwide, but the causal mechanism remains debated among different human-related threats. Coping with this uncertainty is critical to several issues about the conservation and future of biodiversity, but remains challenging due to difficulties associated with the experimental manipulation and/or isolation of the effects of such threats under field conditions. Using controlled microcosm populations, we quantified the individual and combined effects of environmental warming, overexploitation and habitat fragmentation on population persistence. Individually, each of these threats produced similar and significant population declines, which were accelerated to different degrees depending upon particular interactions. The interaction between habitat fragmentation and harvesting generated an additive decline in population size. However, both of these threats reduced population resistance causing synergistic declines in populations also facing environmental warming. Declines in population size were up to 50 times faster when all threats acted together. These results indicate that species may be facing risks of extinction higher than those anticipated from single threat analyses and suggest that all threats should be mitigated simultaneously, if current biodiversity declines are to be reversed. PMID- 17284408 TI - Dispersive and non-dispersive waves through plants: implications for arthropod vibratory communication. AB - Vibratory communication in arthropods is a widespread phenomenon. Arthropods living on plants have been reported to use only dispersive bending waves in the context of prey-predator, competition, social and sexual interactions. Differences in signal structure have also been postulated to work as species recognition mechanisms and speciation agents. Using two identical laser Doppler vibrometers and a wavelet analysis, we quantified the wave propagation modes in rush stems (Juncus effusus) over the whole range of frequencies used by arthropods. A non-dimensionalized analysis shows that mechanical waves propagate not only as dispersive bending waves, but also as non-dispersive waves. Our analysis implies that an arthropod can communicate through non-dispersive bending waves by either producing signals of high frequencies or by choosing large stems, two widely different options tapping into the physiological and the behavioural repertoires, respectively. Non-dispersive waves, unreported so far in insect vibratory communication in plants, present serious advantages over dispersive bending waves in terms of signal integrity and may well be much more widely used than anticipated, in particular for species recognition. PMID- 17284409 TI - Phylogenetic history underlies elevational biodiversity patterns in tropical salamanders. AB - Elevational variation in species richness is ubiquitous and important for conservation, but remains poorly explained. Numerous studies have documented higher species richness at mid-elevations, but none have addressed the underlying evolutionary and biogeographic processes that ultimately explain this pattern (i.e. speciation, extinction and dispersal). Here, we address the evolutionary causes of the mid-elevational diversity hump in the most species-rich clade of salamanders, the tropical bolitoglossine plethodontids. We present a new phylogeny for the group based on DNA sequences from all 13 genera and 137 species. Using this phylogeny, we find no relationship between rates of diversification of clades and their elevational distribution, and no evidence for a rapid 'species pump' in tropical montane regions. Instead, we find a strong relationship between the number of species in each elevational zone and the estimated time when each elevational band was first colonized. Mid-elevation habitats were colonized early in the phylogenetic history of bolitoglossines, and given similar rates of diversification across elevations, more species have accumulated in the elevational zones that were inhabited the longest. This pattern may be widespread and suggests that mid-elevation habitats may not only harbour more species, but may also contain more phylogenetic diversity than other habitats within a region. PMID- 17284410 TI - The visual processing of motion-defined transparency. AB - Our understanding of how the visual system processes motion transparency, the phenomenon by which multiple directions of motion are perceived to coexist in the same spatial region, has grown considerably in the past decade. There is compelling evidence that the process is driven by global-motion mechanisms. Consequently, although transparently moving surfaces are readily segmented over an extended space, the visual system cannot separate two motion signals that coexist in the same local region. A related issue is whether the visual system can detect transparently moving surfaces simultaneously or whether the component signals encounter a serial 'bottleneck' during their processing. Our initial results show that, at sufficiently short stimulus durations, observers cannot accurately detect two superimposed directions; yet they have no difficulty in detecting one pattern direction in noise, supporting the serial-bottleneck scenario. However, in a second experiment, the difference in performance between the two tasks disappears when the component patterns are segregated. This discrepancy between the processing of transparent and non-overlapping patterns may be a consequence of suppressed activity of global-motion mechanisms when the transparent surfaces are presented in the same depth plane. To test this explanation, we repeated our initial experiment while separating the motion components in depth. The marked improvement in performance leads us to conclude that transparent motion signals are represented simultaneously. PMID- 17284411 TI - Social recognition in wild fish populations. AB - The ability of animals to gather information about their social and physical environment is essential for their ecological function. Odour cues are an important component of this information gathering across taxa. Recent laboratory studies have revealed the importance of flexible chemical cues in facilitating social recognition of fishes. These cues are known to be mediated by recent habitat experience and fishes are attracted to individuals that smell like themselves. However, to be relevant to wild populations, where animals may move and forage freely, these cues would have to be temporally flexible and allow spatial resolution. Here, we present data from a study of social recognition in wild populations of three-spined sticklebacks (Gasterosteus aculeatus). Focal fish preferentially associated with conspecifics from the same habitat as themselves. These preferences were changed and updated following translocation of the focal fish to a different site. Further investigation revealed that association preferences changed after 3 h of exposure to different habitat cues. In addition to temporal flexibility, the cues also allowed a high degree of spatial resolution: fish taken from sites 200 m apart produced cues that were sufficiently different to enable the focal fish to discriminate and associate with fish captured near their own home site. The adaptive benefits of this social recognition mechanism remain unclear, though they may allow fish to orient within their social environment and gain current local information. PMID- 17284412 TI - Female butterflies prefer males bearing bright iridescent ornamentation. AB - Butterflies are among nature's most colorful animals, and provide a living showcase for how extremely bright, chromatic and iridescent coloration can be generated by complex optical mechanisms. The gross characteristics of male butterfly colour patterns are understood to function for species and/or sex recognition, but it is not known whether female mate choice promotes visual exaggeration of this coloration. Here I show that females of the sexually dichromatic species Hypolimnas bolina prefer conspecific males that possess bright iridescent blue/ultraviolet dorsal ornamentation. In separate field and enclosure experiments, using both dramatic and graded wing colour manipulations, I demonstrate that a moderate qualitative reduction in signal brightness and chromaticity has the same consequences as removing the signal entirely. These findings validate a long-held hypothesis, and argue for the importance of intra- versus interspecific selection as the driving force behind the exaggeration of bright, iridescent butterfly colour patterns. PMID- 17284413 TI - Rapid courtship evolution in grouse (Tetraonidae): contrasting patterns of acceleration between the Eurasian and North American polygynous clades. AB - Sexual selection is thought to be a powerful diversifying force, based on large ornamental differences between sexually dimorphic species. This assumes that unornamented phenotypes represent evolution without sexual selection. If sexual selection is more powerful than other forms of selection, then two effects would be: rapid divergence of sexually selected traits and a correlation between these divergence rates and variance in mating success in the ornamented sex. I tested for these effects in grouse (Tetraonidae). For three species pairs, within and among polygynous clades, male courtship characters had significantly greater divergence than other characters. This was most pronounced for two species in Tympanuchus. In the Eurasian polygynous clade, relative courtship divergence gradually increased with nucleotide divergence, suggesting a less dramatic acceleration. Increase in relative courtship divergence was associated with mating systems having higher variance in male mating success. These results suggest that sexual selection has accelerated courtship evolution among grouse, although the microevolutionary details appear to vary among clades. PMID- 17284415 TI - Recent network evolution increases the potential for large epidemics in the British cattle population. AB - Following the foot and mouth disease epidemic in Great Britain (GB) in 2001, livestock movement bans were replaced with mandatory periods of standstill for livestock moving between premises. It was anticipated that these movement restrictions would limit each individual's contact networks, the extent of livestock movements and thus the spread of future disease outbreaks. However, the effect of behaviour changes on the global network in adapting to these restrictions is currently unknown. Here, we take a novel approach using GB cattle movement data to construct week-by-week contact networks between animal holdings (AH) to explore the evolution of the network since this policy was introduced, the first time network theory has been used for this purpose. We show that the number of AH moving cattle as part of the giant strong component (GSC), representing the region of maximal connectivity, has been increasing linearly over time. This is of epidemiological significance as the size of the GSC indicates the number of holdings potentially exposed to disease, thus giving a lower bound of maximum epidemic size. Therefore, despite restriction of cattle movements, emergent behaviour in this self-organizing system has potentially increased the size of infectious disease epidemics within the cattle industry. PMID- 17284414 TI - Stem cell myths. AB - Stem cells, although difficult to define, hold great promise as tools for understanding development and as therapeutic agents. However, as with any new field, uncritical enthusiasm can outstrip reality. In this review, we have listed nine common myths that we believe affect our approach to evaluating stem cells for therapy. We suggest that careful consideration needs to be given to each of these issues when evaluating a particular cell for its use in therapy. Data need to be collected and reported for failed as well as successful experiments and a rigorous scientific approach taken to evaluate the undeniable promise of stem cell biology. PMID- 17284416 TI - [Detection and controlling for population stratification in association studies of human complex disease]. AB - Case-control studies, which serve as standard design for genetic association analysis, can be the most practical and powerful approach to detect genetic polymorphisms contributing to susceptibility to complex human diseases. However, considerable concern has been expressed that this approach is prone to population stratification, which can lead to biased or spurious results. We review several methods to detect and account for population stratification; these methods include nuclear family-based transmission/disequilibrium test (TDT), and genomic control (GC) and structured association (SA) based on unlinked genetic markers. PMID- 17284418 TI - [Effect of fertilization condition on mammalian sex determination]. AB - Selection of sex at or before conception is perhaps the most desired biotechnology of all time because many economic traits are related with sex. Sex selection by manipulating the conditions of sperm-oocytes fertilization would be one of the most practicable and widely used methods. This review summarized the progress in the effects of fertilization conditions on mammalian sex. Four main factors which possibly affected sex were described such as arginine concentration in female animal vagina, glucose in the uterus, maturational status of the oocyte at the time they encounter sperm as well as the hormone levels of both parents at the time of conception. PMID- 17284417 TI - [Research progress of lipoprotein lipase gene]. AB - Lipoprotein lipase is a central enzyme in the lipid metabolism, which catalyses the hydrolysis of the triacylglycerol component of chylomicrons and very low density lipoproteins, thereby providing fatty acids and monoacylglycerol for tissue utilisation. LPL gene mutation may affect the activity of LPL, and results in lipid metabolism disorder. It is associated with type 2 diabetes, hypertension, atherosclerosis, obesity and coronary artery disease. Here we review the structure, function, expression regulation of the LPL gene along with its association with complex diseases. PMID- 17284419 TI - [RNA silencing and its application in plant]. AB - RNA silencing is an ancient phenomenon commonly existed in organisms, which acts as the mechanism of self-protection in defending abnormal DNA and as the gene expression regulator during the growth and development of organisms. The hotspots about RNA silencing and the methods of this technique used in plants according to its durational differences were introduced. The current status and prospective of the technique in the areas of plant functional genomics studies, improvement of crop quality, and plant breeding for virus resistance were reviewed. PMID- 17284420 TI - [Recent advances in plant virus vector systems]. AB - Most plant viral genome is relatively small and easy for genetic manipulation and inoculation. Therefore, plant viral vectors are attractive tools for expression foreign genes in plants. This paper reviews two basic types of epitope presentation and polypeptide expression systems, and discusses the development and application prospect of plant virus vector. PMID- 17284421 TI - [Detection of two novel mutations of iduronate-2-sulfatase gene in patients with mucopolysaccharidosis type II]. AB - In the present study, through PCR amplification and direct sequencing of mutation "hotspots", we were able to identify two novel mutations in the human iduronate-2 sulfatase (IDS) gene in two patients from unrelated families with mucopolysaccharidosis type II(MPS II). The novel mutation IVS 6 -1g-->a affected the 3' splice acceptor site of intron 6, and was predicted to result in exon skipping. The novel mutation c.1587-1588 ins T involved a single base insertion be-tween nucleotides 1,587 and 1,588 in exon 9, and was predicted to result in frame shift and premature termination. The two novel mutations did not occur in 6 other unrelated MPS patients or in 100 alleles from normal individuals, indicating that they were not polymorphisms. The PCR-restriction enzyme digestion showed that the two newly identified mutations were of maternal origin, which was consistent with the X-linked recessive disorder. These findings suggest that the IDS gene mutations could be detected by amplifying mutation "hotspots", direct sequencing and restriction digestion analysis, and the newly identified mutations may be disease-causing. PMID- 17284422 TI - [An association study between GRIN1, BDNF genes and bipolar disorder]. AB - To evaluate the role of inherited gene variations in GRIN1 (glutamate receptor, ionotropic NMDA1), BDNF (brain derived neurotrophic factor) genes in human bipolar disorder, we selected 4 single nucleotide polymorphisms in GRIN1, BDNF (2 SNPs in each gene) and made SNPs analysis in 100 unrelated cases and 100 controls by TaqMan. Then we compared genotypes differences between cases and controls. The software SHEsis was also used to make haplotype analysis. The significant results were obtained, showing that the SNPs in GRIN1 gene were related to the BP (P < 0.05). In addition, the combined haplotype T/G had a significant difference in the two groups (P < 0.05). The SNPs in BDNF gene showed no statistical significance. These results confirm that the GRIN1 gene confers susceptibility to bipolar disorder. PMID- 17284423 TI - [Preliminary study on the relationship between sow maternal behaviour during early lactation and polymorphism of PRLR gene]. AB - PCR-RFLP technique was applied to analyze single nucleotide polymorphisms of PRLR gene in Minpig and Landrace to investigate the possible effect of PRLR gene on sow maternal behaviour. A Nae I-RFLP site was detected in the PRLP gene. The single nucleotide polymorphism, a T-->C transition at nucleotide 1,620 of the cDNA sequence, was a silent mutation. Least square analysis between the genotypes and the maternal behavioural traits showed that sows with genotype AB had a significantly higher frequency of lateral-lying-to- other-posture trait and percentage of sow-terminated nursing trait than sows with the AA and BB genotypes, although no significant differences were found in other behavioural traits. It is possible that allele A is the unfavorable allele for sow maternal behaviour. PMID- 17284424 TI - [FUT1 gene polymorphism and its association with litter size in pigs]. AB - The genetic variations of FUT1 gene at nucleotide position 307 of its open reading frame were investigated by PCR-RFLP in a total of 245 pigs from 3 exotic pig breeds and 3 Chinese native pig breeds. Results showed that the genetic polymorphisms of the FUT1 locus were only detected in the 3 exotic pig breeds. There were 3 different genotypes and the majority were the susceptible forms including GG and AG. All Chinese native pig breeds only presented the susceptible genotype GG. Univariate analysis of variance components indicated that FUT 1 gene and the type of breeds significantly affected total number born, whereas parities did not. None of these factors significantly affected the number of liveborns. PMID- 17284425 TI - [Single nucleotide polymorphism analysis on the 5' regulatory region of IGF2 gene in Wuzhishan pig]. AB - Single nucleotide polymorphisms (SNPs) in partial 5' regulatory region of the insulin-like growth factor 2 (IGF2) gene were studied by DNA sequencing in 60 pigs from the Wuzhishan, Diannan small-ear, Xiang, Meishan and Large White pig breeds. Thirteen SNP sites were detected, including one transversion at T6029A, 4 A<---->G transitions (A5976G, G13520A, G13563A and G13669A) and 8 C<---->T transitions (C5872T, C5888T, C6010T, C6037T, C6043T, C6063T,C6112T, C6164T). These 13 SNPs formed 23 composite genotypes. The gene, genotype and composite genotype frequencies of every SNP site in the whole group and in each breed were calculated. Results showed that the predominant allele in 3 miniature pig breeds was G, T and A at A5976G, C6164T and G13669A sites respectively, but the A-C-G allele was pre-dominant in Meishan and Large White breeds. Moreover, H15 and H19 were the characteristic composite genotype for the large versus the miniature breeds, respectively. In addition, the C5888T SNP was analyzed in 123 Wuzhishan pigs by the PCR-RFLP method. Results showed that the predominant allele was C, and the predominant genotype was CC. chi2-test results indicated that the Wuzhishan pig breed was at Hardy-Weinberg equilibrium with respect to this SNP. These results provide the miniature pig breeds such as the Wuzhishan pig with certain genetic references on the regulation of growth and development, and the mechanism of its dwarfism. PMID- 17284427 TI - [Candidate gene analysis of high quality merino sheep]. AB - Partial sequences of wool fiber constituent genes KAP1.1 and KAP1.3 and the exonic sequence of the KAP6.1 gene were chosen for polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) analysis to assess their ability as candidate genes during indirect selection for fine wool traits. Results show that locus W08667 in the genes (KAP1.1, KAP1.3) which code the high sulfur protein associated-protein of keratin associated-protein family is significantly correlated with fine wool quality (P < 0.05). Among the high glycine-tyrosine keratin associated- protein, the AA and BB genotypes of W06933 are also significantly correlated with fine wool quality (P < 0.05). PMID- 17284426 TI - [Correlation between porcine CAST gene polymorphism with muscle fiber histological traits and carcass characteristics]. AB - Three polymorphisms were identified in the sixth intron of the CAST gene by PCR RFLP using enzymes Msp I, Hinf I and Rsa I in 45 Jinpi F2 pigs. However, only three genotypes AACCEE, BBDDFF, and ABCDEF were detected in those pigs and the genotype frequencies were 0.1778, 0.2222 and 0.6000, respectively. Longissimus dorsi muscles were moved for paraffin serial sections and stained with hematoxylin-eosin or myosin heavy chain (MHC) by immunohistochemistry respectively. Fiber cross-sectional area, fiber density, fiber diameter, the rate of MHC type I fiber and the carcass characteristics were recorded. Correlation analysis showed that the skeletal muscle fiber area and the eye muscle area of the BBDDFF individual were significantly higher than those of the ABCDEF individual (P < 0.05). PMID- 17284428 TI - [Differential gene expression of hypoxia inducible factor-1alpha and hypoxic adaptation in chicken]. AB - Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor first discovered in cancer cells under hypoxic conditions, and was demonstrated to play a key role in the organism's adaptation to changing oxygen tensions. The Tibetan chicken, a breed indigenous to the Tibetan plateau is particularly adaptable to the low oxygen tension and low temperature conditions in the high altitude environment. By comparison, the White Leghorn and ShouGuang chicken are low-altitude chicken breeds. The eggs of these three chicken breeds were incubated in a fitted hatcher that simulated hypoxic condition. The results demonstrated that the hatching rate for Tibetan chicken was significantly higher than the two low altitude breeds, and Tibetan chicken displayed higher endurance in the hypoxia environment. To a certain degree, the hypoxic condition proved fatal to hatching for the low altitude chickens. Gene expression of HIF-1alpha was detected in brain and skeletal muscle tissues for three chicken varieties using the TaqMan probe FQRT PCR method. The results showed that HIF-1alpha mRNA displayed tissue specific differential expression, with the highest in the brain. In addition, the expression of HIF-1alpha mRNA in the brain of Tibetan chicken embryos was similar to that of the low-altitude chickens when they were hatched under normal oxygen tensions. PMID- 17284429 TI - [mRNA expression of genes related to avian sex determination during female-to male sex reversal in ZW chicken embryos]. AB - Dsx and mab-3-related transcription factor (DMRT1), Protein kinase C inhibitor (PKCIW) and Female-specific expression transcription factor (FET1) have been regarded as critical candidates of avian sex determination. Their mRNA expression was analyzed in chicken embryos during experimentally induced female-to-male sex reversal by an aromatase inhibitor (AI) fadrozole. DMRT1 expression was higher in male (ZZ) gonads than in female (ZW) gonad prior to and throughout the period of sex differentiation. However, female-to-male sex-reversed ZW embryos showed elevated levels of DMRT1 expression similar to those of normal males, indicating that DMRT1 was associated with testis development. PKCIW gene expression was dimorphic between male and female gonads, and was up-regulated in AI-treated female embryos. This finding might account for the specific effect of PKCIW, functioning via heterodimerization with PKCI during avian sex determination. However, its elevated expression appeared to be insufficient to induce ovary development. On the other hand, FET1 expression was female-specific and unchanged in AI-treated female embryos. Results of present experiment suggested that DMRT1 is a determinant for testis development in birds. PMID- 17284430 TI - [Cloning and characterization of a novel trinucleotide repeat-containing gene GARP from Euplotes octocarinatus]. AB - The expansion of trinucleotide repeats in genome is related to the phthogenesis of several neurodegenerative diseases. A GARP (glutamic acid-rich protein) gene was isolated from the macronuclear plasmid mini library of Euplotes octocarinatus. A micronuclear version of the GARP gene was amplified by polymerase chain reaction. The macronuclear DNA molecule carrying the GARP gene is 460 bp long and shows the characteristics of macronuclear chromosomes of hypotrichous ciliates. One of the three cysteines is encoded by the opal codon TGA(88-90). The predicted open reading frame encodes a 112-amino acid polypeptide, with a predicted molecular mass of 13 kDa and an isoelectric point of 3.82. Micronuclear version of the GARP gene contains two internal eliminated sequences (IES), IES1 and IES2. IES1 is 41 bp long and is flanked by 5'-GA-3' direct repeats. IES2 is 41 bp long and flanked by 5'-TA-3' direct repeats. Transcriptional activity of GARP gene was confirmed by reverse transcription polymerase chain reaction (RT-PCR). PMID- 17284431 TI - [Mapping QTLs related to oil content of soybeans]. AB - The soybean Recombinant Inbred Lines(RIL), including 133 lines, from the cross Wan82-178 x Tongshan-baopihuangdoujia were used as experimental materials in this study. Based on the linkage map constructed with Single Sequence Repeat(SSR) markers using this RIL population, the software Cartgrapher(V.2.0) and the composite interval mapping were employed to identify quantitative traits loci(QTL) associated with oil content of soybean in 2004 and 2005. It was found that the results of mapping QTL for the oil content were similar for these two years. They were both mapped near satt331 on linkage group wt-11, and they could be used to explain 13.95% and 15.01% of the total variation of the oil content, respectively. In addition, the software QTL Mapper 1.6 was applied to detect QTLs related to oil con-tent in two years. The result indicated that the QTL related to oil content was still mapped near satt331 on linkage group wt-11. PMID- 17284432 TI - [Transgenic wheat expressing virus-derived hairpin RNA is resistant to Barley yellow dwarf virus]. AB - An expression vector expected to induce RNA interference against Barley yellow dwarf virus (BYDV), which expressed a composite hpRNA with the dsRNA stem homologous of BYDV GPV replicase gene and the antisense RNA loop homologous of coat protein gene, was designed without marker gene. The vector was transferred into callus cells from wheat (Triticum aestivum L.) immature embryos by particle bombardment. To select the positive transformants as early as possible, a rapid PCR, which does not need extract wheat DNA instead of few leaves, was used at regeneration stage of plantlets. Totally 21 plants proved to contain alien sequence. Antivirus test with high dose infected virus revealed that, 9 plants showed low level of resistance to BVDV, 6 plants showed moderate resistance and 6 plants showed high level of resistance. Interestingly, both low and moderate levels of resistance plants were no symptoms when infected by viruses at low dose. It suggests the dose- dependent effect of the resistance mediated by hpRNA to BYDV-GPV. PMID- 17284433 TI - [Studies on tea plants (Camellia sinensis) germplasms using EST-SSR marker]. AB - Forty two tea varieties were analyzed by using 16 SSR primer sets derived from tea ESTs in this study, and 13 of the primer sets produced clear bands and 10 of them showed polymorphism, accounting for 76.9%. The PIC (polymorphism information content) for each polymorphic primer set varied from 0.522 to 0.866, with a average about 0.73. Totally 84 Genotypes and 74 alleles were detected in all materials by 10 polymorphic markers, with the range from 4 to 12 and from 3 to 10 for each polymorphic primer set, respectively. The genetic distance among 42 tea varieties varied from 0.074 to 0.667, averagely 0.363, suggesting that the materials used in the experiment possess a broad genetic variation. Based on the similarity coefficient about 0.55, all the tea varieties tested could be classified into 3 groups and most of them were in first group. The results of this study proved that the EST-SSR marker is very effective in evaluation of tea germplasms. PMID- 17284434 TI - [Cloning and evolutionary analysis of homologous sequences of SAMDC gene in Cruciferae]. AB - S-adenosylmethionine decarboxylase activity (SAMDC) is a key enzyme involved in biosynthesis of the polyamines, viz. spermidine and spermine. In the present study, SAMDC gene analogues from 14 species of 6 genera in Cruciferae were obtained by PCR strategy using specific primers designed from conserved regions of SAMDC gene reported in the GenBank. The phylogenetic relationships of these species belonging to the family Cruciferae were investigated through comparison of the genes. Homologous sequences of SAMDC comparison indicated that the similarities among the genes at nucleotide and amino acid levels were over 87% and 90%, respectively. The differences in genes at nucleotide and amino acid levels between species ranged from 0.2 % to 10.1 % and 0.3% to 6.6%, respectively, while those between genera except Raphanus were 4.9 % to 13.6 % and 3.1 % to 10.3%, respectively. The differences of sequences of nucleotides and amino acids among genera were higher than those among species, and the differences of nucleotides sequences were higher than those of amino acids. The phylogenetic tree was thus constructed based on the alignment nucleotides sequences from Nei's genetic distances. The neighbor-joining (NJ) and minimum evolution (ME) trees showed that Brassica was closely related to Raphanus, followed by Barbarea, Roripl Scop and Arabidopsis Heynh, but was remotely related to Capsella Medic. This research elucidated the relationship among crucifer species at nucleotide level, which could proved some help for the utilization of plant germplasms. PMID- 17284435 TI - [Phylogenetic and genetic analysis of symbiotic nodulation genes within the Bradyrhizobium]. AB - Symbiotic nitrogen fixing bacteria-known as rhizobia-harbour a set of nodulation (nod) genes that control the synthesis of modified lipo-chitooligosaccharides, called Nod factors that are required for legume nodulation. The nodA gene, which is essential for symbiosis, is responsible for the attachment of the fatty acid group to the oligosaccharide backbone. The nodZ, nolL, and noeI genes are involved in specific modifications of Nod factors common to bradyrhizobia, i.e., the transfer of a fucosyl group on the Nod factor core, fucose acetylation and fucose methylation, respectively. The distribution of the nodZ, nolL, and noeI genes in the studied strains was found to correlate with the nodA tree topology. Moreover, the nodA, nodZ, and noeI phylogenies were largely congruent, but did not closely follow the taxonomy of the strains shown by the housekeeping 16S rRNA and dnaK genes. Additionally, the distribution of nodZ, noeI, and nolL genes suggested that their presence may be related to the requirements of their legume hosts. These data indicated that the spread and maintenance of nodulation genes within the Bradyrhizobium genus occurred through vertical transmission, although lateral gene transfer also played a significant role. PMID- 17284436 TI - Sexual dysfunction in dialysis patients treated with antihypertensive or antidepressive medications: results from the DOPPS. AB - BACKGROUND: The relationship between medication prescription and sexual dysfunction (SD) in dialysis patients is unclear. METHODS: We studied antihypertensive and antidepressive agents prescribed for 7346 patients in the Dialysis Outcomes and Practice Patterns Study phase 1 (DOPPS I) and 8891 patients in DOPPS II. At baseline, DOPPS I patients completed a quality of life survey, including four questions about sexual functioning, from which we created a composite SD scale. DOPPS II patients were asked only one question about SD. We examined predictors of SD with logistic regression, using numerous patient characteristics, comorbid conditions and additional variables. RESULTS: Reported SD ranged from 66.4% (France) to 84.5% (Spain). The mean composite SD score ranged from 6.4 (Spain) to 7.9 (Germany) (on a 3-15 scale). Peripheral alpha blockers increased odds of DOPPS I patients having their sex life bothered by end stage renal disease (ESRD) (OR=1.18), and there were elevated odds of arousal problems with central antagonists, loop diuretics and peripheral alpha-blockers (OR=1.19, 1.24 and 1.29, respectively). Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines increased odds of problems with enjoyment (OR=1.59 and 1.26, respectively) and arousal (OR=1.70 and 1.24, respectively), and having sex life bothered by ESRD (DOPPS I: OR=1.36 and 1.24; DOPPS II: 1.30 and 1.31, respectively). Vasodilators reduced the odds of sexual enjoyment problems (OR=0.75). Composite SD scores worsened with peripheral alpha-blockers (+0.41), tricyclics (+0.78), SSRIs (+0.80) and benzodiazepines (+0.50), but not with vasodilators (-0.57). CONCLUSIONS: Awareness of associations between SD and prescribed medications may offer opportunities for intervention. PMID- 17284437 TI - The spatial distribution of inositol 1,4,5-trisphosphate receptor isoforms shapes Ca2+ waves. AB - Cytosolic Ca(2+) is a versatile second messenger that can regulate multiple cellular processes simultaneously. This is accomplished in part through Ca(2+) waves and other spatial patterns of Ca(2+) signals. To investigate the mechanism responsible for the formation of Ca(2+) waves, we examined the role of inositol 1,4,5-trisphosphate receptor (InsP3R) isoforms in Ca(2+) wave formation. Ca(2+) signals were examined in hepatocytes, which express the type I and II InsP3R in a polarized fashion, and in AR4-2J cells, a nonpolarized cell line that expresses type I and II InsP3R in a ratio similar to what is found in hepatocytes but homogeneously throughout the cell. Expression of type I or II InsP3R was selectively suppressed by isoform-specific DNA antisense in an adenoviral delivery system, which was delivered to AR4-2J cells in culture and to hepatocytes in vivo. Loss of either isoform inhibited Ca(2+) signals to a similar extent in AR4-2J cells. In contrast, loss of the basolateral type I InsP3R decreased the sensitivity of hepatocytes to vasopressin but had little effect on the initiation or spread of Ca(2+) waves across hepatocytes. Loss of the apical type II isoform caused an even greater decrease in the sensitivity of hepatocytes to vasopressin and resulted in Ca(2+) waves that were much slower and delayed in onset. These findings provide evidence that the apical concentration of type II InsP3Rs is essential for the formation of Ca(2+) waves in hepatocytes. The subcellular distribution of InsP3R isoforms may critically determine the repertoire of spatial patterns of Ca(2+) signals. PMID- 17284438 TI - Rescue of calcium-sensing receptor mutants by allosteric modulators reveals a conformational checkpoint in receptor biogenesis. AB - The calcium-sensing receptor (CaR), a member of G protein-coupled receptor family C, regulates systemic calcium homeostasis by activating G(q)- and G(i)-linked signaling in the parathyroid, kidney, and intestine. CaR is ubiquitinated by the E3 ligase dorfin and degraded via the endoplasmic reticulum-associated degradation pathway (Huang, Y., Niwa, J., Sobue, G., and Breitwieser, G. E. (2006) J. Biol. Chem. 281, 11610-11617). Here we provide evidence for a conformational or functional checkpoint in CaR biogenesis using two complementary approaches. First we characterized the sensitivity of loss- or gain-of-function CaR mutants to proteasome inhibition by MG132. The stabilization of loss-of function mutants and insensitivity of gain-of-function mutants to MG132 suggests that receptor sensitivity to calcium influences susceptibility to proteasomal degradation. Second, we used the allosteric activator NPS R-568 and antagonist NPS 2143 to promote the active and inactive conformations of wild type CaR, respectively. Overnight culture in NPS R-568 increased expression of CaR, whereas NPS 2143 had the opposite effect. NPS R-568 and NPS 2143 differentially regulated maturation and cell surface expression of wild type CaR, directly affecting maximal signaling responses. NPS R-568 rescued expression of loss-of-function CaR mutants, increasing plasma membrane expression and ERK1/2 phosphorylation in response to 5 mM Ca(2+). Disorders of calcium homeostasis caused by CaR mutations may therefore result from altered receptor biogenesis independent of receptor function, i.e. a protein folding disorder. The allosteric modulators NPS R-568 and NPS 2143 not only alter CaR sensitivity to calcium and hence signaling but also modulate receptor expression. PMID- 17284439 TI - Protein kinase C regulates internal initiation of translation of the GATA-4 mRNA following vasopressin-induced hypertrophy of cardiac myocytes. AB - GATA-4 is a key member of the GATA family of transcription factors involved in cardiac development and growth as well as in cardiac hypertrophy and heart failure. Our previous studies suggest that GATA-4 protein synthesis may be translationally regulated. We report here that the 518-nt long 5'-untranslated region (5'-UTR) of the GATA-4 mRNA, which is predicted to form stable secondary structures (-65 kcal/mol) such as to be inhibitory to cap-dependent initiation, confers efficient translation to monocistronic reporter mRNAs in cell-free extracts. Moreover, uncapped GATA-4 5'-UTR containing monocistronic reporter mRNAs continue to be well translated while capped reporters are insensitive to the inhibition of initiation by cap-analog, suggesting a cap-independent mechanism of initiation. Utilizing a dicistronic luciferase mRNA reporter containing the GATA-4 5'-UTR within the intercistronic region, we demonstrate that this leader sequence confers functional internal ribosome entry site (IRES) activity. The activity of the GATA-4 IRES is unaffected in trans-differentiating P19CL6 cells, however, is strongly stimulated immediately following arginine vasopressin exposure of H9c2 ventricular myocytes. IRES activity is then maintained at submaximal levels during hypertrophic growth of these cells. Supraphysiological Ca(2+) levels diminished stimulation of IRES activity immediately following exposure to vasopressin and inhibition of protein kinase C activity utilizing a pseudosubstrate peptide sequence blocked IRES activity during hypertrophy. Thus, our data suggest a mechanism for GATA-4 protein synthesis under conditions of reduced global cap-dependent translation, which is maintained at a submaximal level during hypertrophic growth and point to the regulation of GATA-4 IRES activity by sarco(ER)-reticular Ca(2+) stores and PKC. PMID- 17284440 TI - Non-apoptotic phosphatidylserine externalization induced by engagement of glycosylphosphatidylinositol-anchored proteins. AB - The exposure of phosphatidylserine (PS) on the cell surface is a general marker of apoptotic cells. Non-apoptotic PS externalization is induced by several activation stimuli, including engagement of immunoreceptors. Immune cells can also be activated by aggregation of glycosylphosphatidylinositol-anchored proteins (GPI-APs). However, it is unknown whether cell triggering through these proteins, lacking transmembrane and cytoplasmic domains, also leads to PS externalization. Here we show that engagement of GPI-APs in rodent mast cells induces a rapid and reversible externalization of PS by a non-apoptotic mechanism. PS externalization triggered by GPI-AP-specific monoclonal antibodies was dependent on the activity of H(+)-ATP synthase and several other enzymes involved in mast cell signaling but was independent of cell degranulation, free cytoplasmic calcium up-regulation, and a decrease in lipid packing as determined by merocyanine 540 binding. Surprisingly, disruption of actin cytoskeleton by latrunculin B or plasma membrane integrity by methyl-beta-cyclodextrin had opposite effects on PS externalization triggered through GPI-AP or the high affinity IgE receptor. We further show that PS externalization mediated by GPI APs was also observed in some other cells, and its extent varied with antibodies used. Interestingly, effects of different antibodies on PS externalization were additive, indicating that independent stimuli converge onto a signaling pathways leading to PS externalization. Our findings identify the cell surface PS exposure induced through GPI-AP as a distinct mechanism of cell signaling. Such a mechanism could contribute to "inside-out" signaling in response to pathogens and other external activators and/or to initiation of other functions associated with PS externalization. PMID- 17284441 TI - Epidermal growth factor directs sex-specific steroid signaling through Src activation. AB - Estrogens and androgens exert many biological effects that do not require interactions of their receptors with chromosomal DNA. However, it has been a long standing question how the sex steroid receptors provoke signal transduction outside the nucleus. Here we have shown that epidermal growth factor (EGF) directs sex-specific steroid signaling through Src activation. We have revealed that estrogen (E2)-induced Src activation takes place in, not only plasma, but also endomembranes. This was found ascribed to the existence of EGF and the occurrence of EGF receptor (EGFR)-involved endocytosis of estrogen receptor together with Src. EGFR, estrogen receptor, and Src were found to form a complex upon E2 stimulation. The cell growth of breast cancer-derived MCF-7 cells was found to remarkably increase through the above EGF-involved estrogen-signaling process. In contrast, the androgen 5alpha-dihydrotestosterone-induced Src activation occurs only in the plasma membrane free from the interaction of EGFR with androgen receptor, irrespective of EGF. The cell growth occurred only moderately as a result. The spatial difference in Src activation between E2 and 5alpha-dihydrotestosterone may be responsible for the different extent of observed cell growth. PMID- 17284442 TI - The gap junction protein connexin32 interacts with the Src homology 3/hook domain of discs large homolog 1. AB - Scaffolding of membrane proteins is a common strategy for forming complexes of proteins, including some connexins, within membrane microdomains. Here we describe studies indicating that Cx32 interacts with a PDZ-containing scaffolding protein, Dlgh1 (Discs Large homolog 1). Initial screens of liver lysates using antibody arrays indicated an interaction between Cx32 and Dlgh1 that was confirmed using coimmunoprecipitation studies. Yeast two-hybrid complementation determined that the Cx32 bound via interaction with the SH3/Hook domain of Dlgh1. Confocal microscopy of liver sections revealed that Cx32 and Dlgh1 could colocalize in hepatocyte membranes in wild type mice. Examination of levels and localization of Dlgh1 in livers from Cx32 null mice indicate that, in the absence of Cx32, Dlgh1 was decreased, and the remainder was translocated from the hepatocyte membrane to the nucleus with some remaining in cytoplasmic compartments. This translocation was confirmed by Western blots comparing Dlgh1 levels in nuclear extracts from wild type and Cx32 null murine livers. Using SKHep cells stably transfected with Cx32 under the control of a tet-off promoter, we found that acute removal of Cx32 led to a decrease of membrane-localized Dlgh1 and an increase in the nuclear localization of this tumor suppressor protein. Together, these results suggest that loss of Cx32 alters the levels, localization, and interactions of the tumor suppressor protein Dlgh1, events known in other systems to alter cell cycle and increase tumorigenicity. PMID- 17284444 TI - Deafness and stria vascularis defects in S1P2 receptor-null mice. AB - The S1P(2) receptor is a member of a family of G protein-coupled receptors that bind the extracellular sphingolipid metabolite sphingosine 1-phosphate with high affinity. The receptor is widely expressed and linked to multiple G protein signaling pathways, but its physiological function has remained elusive. Here we have demonstrated that S1P(2) receptor expression is essential for proper functioning of the auditory and vestibular systems. Auditory brainstem response analysis revealed that S1P(2) receptor-null mice were deaf by one month of age. These null mice exhibited multiple inner ear pathologies. However, some of the earliest cellular lesions in the cochlea were found within the stria vascularis, a barrier epithelium containing the primary vasculature of the inner ear. Between 2 and 4 weeks after birth, the basal and marginal epithelial cell barriers and the capillary bed within the stria vascularis of the S1P(2) receptor-null mice showed markedly disturbed structures. JTE013, an S1P(2) receptor-specific antagonist, blocked the S1P-induced vasoconstriction of the spiral modiolar artery, which supplies blood directly to the stria vascularis and protects its capillary bed from high perfusion pressure. Vascular disturbance within the stria vascularis is a potential mechanism that leads to deafness in the S1P(2) receptor null mice. PMID- 17284443 TI - Neural expression of G protein-coupled receptors GPR3, GPR6, and GPR12 up regulates cyclic AMP levels and promotes neurite outgrowth. AB - Cyclic AMP regulates multiple neuronal functions, including neurite outgrowth and axonal regeneration. GPR3, GPR6, and GPR12 make up a family of constitutively active G protein-coupled receptors (GPCRs) that share greater than 50% identity and 65% similarity at the amino acid level. They are highly expressed in the central nervous system, and their expression in various cell lines results in constitutive stimulation of cAMP production. When the constitutively active GPCRs were overexpressed in rat cerebellar granule neurons in culture, the transfected neurons exhibited significantly enhanced neurite outgrowth and overcame growth inhibition caused by myelin-associated glycoprotein. GPR12-mediated neurite outgrowth was the most prominent and was shown to depend on G(s) and cAMP dependent protein kinase. Moreover, the GPR12-mediated rescue from myelin associated glycoprotein inhibition was attributable to cAMP-dependent protein kinase-mediated inhibition of the small GTPase, RhoA. Among the three receptors, GPR3 was revealed to be enriched in the developing rat cerebellar granule neurons. When the endogenous GPR3 was knocked down, significant reduction of neurite growth was observed, which was reversed by expression of either GPR3 or GPR12. Taken together, our results indicate that expression of the constitutively active GPCRs up-regulates cAMP production in neurons, stimulates neurite outgrowth, and counteracts myelin inhibition. Further characterization of the GPCRs in developing and injured mammalian neurons should provide insights into how basal cAMP levels are regulated in neurons and could establish a firm scientific foundation for applying receptor biology to treatment of various neurological disorders. PMID- 17284445 TI - Molecular framework for the activation of RNA-dependent protein kinase. AB - The RNA-dependent protein kinase (PKR) plays an integral role in the antiviral response to cellular infection. PKR contains three distinct domains consisting of two conserved N-terminal double-stranded RNA (dsRNA)-binding domains, a C terminal Ser-Thr kinase domain, and a central 80-residue linker. Despite rich structural and biochemical data, a detailed mechanistic explanation of PKR activation remains unclear. Here we provide a framework for understanding dsRNA dependent activation of PKR using nuclear magnetic resonance spectroscopy, dynamic light scattering, gel filtration, and autophosphorylation kinetics. In the latent state, PKR exists as an extended monomer, with an increase in self affinity upon dsRNA association. Subsequent phosphorylation leads to efficient release of dsRNA followed by a greater increase in self-affinity. Activated PKR displays extensive conformational perturbations within the kinase domain. We propose an updated model for PKR activation in which the communication between RNA binding, central linker, and kinase domains is critical in the propagation of the activation signal and for PKR dimerization. PMID- 17284446 TI - Targeted gene deletion of Leishmania major UDP-galactopyranose mutase leads to attenuated virulence. AB - Considering the high incidence of galactofuranose (Gal(f)) in pathogens and its absence from higher eukaryotes, the enzymes involved in the biosynthesis of this unusual monosaccharide appear as attractive drug targets. However, although the importance of Gal(f) in bacterial survival or pathogenesis is established, its role in eukaryotic pathogens is still undefined. Recently, we reported the identification and characterization of the first eukaryotic UDP-galactopyranose mutases. This enzyme holds a central role in Gal(f) metabolism by providing UDP Gal(f) to all galactofuranosyltransferases. In this work, the therapeutical potential of Gal(f) metabolism in Leishmania major was hence evaluated by targeted replacement of the GLF gene encoding UDP-galactopyranose mutase. In L. major, Gal(f) is present in the membrane anchor of the lipophosphoglycan (LPG) and in glycoinositolphospholipids. Accordingly, the generated glf(-) mutant is deficient in LPG backbone and expresses truncated glycoinositolphospholipids. These structural changes do not influence the in vitro growth of the parasite but lead to an attenuation of virulence comparable with that observed with a mutant exclusively deficient in LPG. PMID- 17284447 TI - Hepatocyte growth factor induces glucose uptake in 3T3-L1 adipocytes through A Gab1/phosphatidylinositol 3-kinase/Glut4 pathway. AB - Adipose tissue is a source of hepatocyte growth factor (HGF), and circulating HGF levels have been associated with elevated body mass index in human. However, the effects of HGF on adipocyte functions have not yet been investigated. We show here that in 3T3-L1 adipocytes HGF stimulates the phosphatidylinositol (PI) 3 kinase-dependent protein kinase B (PKB) activity, AS160 phosphorylation, Glut4 translocation, and consequently, glucose uptake. The initial steps involved in HGF- and insulin-induced glucose uptake are different. HGF enhanced the tyrosine phosphorylation of Gab1, leading to the recruitment of the p85-regulated subunit of PI 3-kinase, whereas p85 was exclusively recruited by IRS1 in response to insulin. In adipocytes rendered insulin-resistant by a long-lasting tumor necrosis factor alpha treatment, the protein level of Gab1 was strongly decreased, and HGF-stimulated PKB activation and glucose uptake were also altered. Moreover, treatment of 3T3-L1 adipocytes with thiazolidinedione, an anti diabetic drug, enhanced the expression of both HGF and its receptor. These data provide the first evidence that in vitro HGF promotes glucose uptake through a Gab1/PI 3-kinase/PKB/AS160 pathway which was altered in tumor necrosis factor alpha-treated adipocytes. PMID- 17284449 TI - Regulation of inositol 1,4,5-trisphosphate 3-kinases by calcium and localization in cells. AB - Inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) 3-kinases (IP(3)Ks) are a group of calmodulin-regulated inositol polyphosphate kinases (IPKs) that convert the second messenger Ins(1,4,5)P(3) into inositol 1,3,4,5-tetrakisphosphate. However, what they contribute to the complexities of Ca(2+) signaling, and how, is still not fully understood. In this study, we have used a simple Ca(2+) imaging assay to compare the abilities of various Ins (1,4,5)P(3)-metabolizing enzymes to regulate a maximal histamine-stimulated Ca(2+) signal in HeLa cells. Using transient transfection, we overexpressed green fluorescent protein-tagged versions of all three mammalian IP(3)K isoforms, including mutants with disrupted cellular localization or calmodulin regulation, and then imaged the Ca(2+) release stimulated by 100 microm histamine. Both localization to the F-actin cytoskeleton and calmodulin regulation enhance the efficiency of mammalian IP(3)Ks to dampen the Ins (1,4,5)P(3)-mediated Ca(2+) signals. We also compared the effects of the these IP(3)Ks with other enzymes that metabolize Ins(1,4,5)P(3), including the Type I Ins(1,4,5)P(3) 5-phosphatase, in both membrane-targeted and soluble forms, the human inositol polyphosphate multikinase, and the two isoforms of IP(3)K found in Drosophila. All reduce the Ca(2+) signal but to varying degrees. We demonstrate that the activity of only one of two IP(3)K isoforms from Drosophila is positively regulated by calmodulin and that neither isoform associates with the cytoskeleton. Together the data suggest that IP(3)Ks evolved to regulate kinetic and spatial aspects of Ins (1,4,5)P(3) signals in increasingly complex ways in vertebrates, consistent with their probable roles in the regulation of higher brain and immune function. PMID- 17284450 TI - Salicylates trigger protein synthesis inhibition in a protein kinase R-like endoplasmic reticulum kinase-dependent manner. AB - The non-steroidal anti-inflammatory drug aspirin and its metabolite, sodium salicylate, have profound effects on cellular protein synthesis and cell physiology. However, the underlying mechanism by which they cause these responses remains unclear. We show here that salicylates induce phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2alpha), resulting in the inhibition of mRNA translation in cells. Exposure of cells to acetyl salicylic acid resulted in strong activation of eIF2alpha stress-activated protein kinase R-like endoplasmic reticulum kinase (PERK). Analysis of fibroblasts with a targeted deletion of the perk gene revealed that PERK is indispensable for triggering the phosphorylation of eIF2alpha as well as the inhibition of protein synthesis induced by salicylates. Although salicylate treatment did not trigger activation of inositol-requiring enzyme 1, there was an increased expression of the pro-apoptotic transcription factor CHOP-(gadd153), a downstream event to eIF2alpha phosphorylation known to mediate endoplasmic reticulum stress-mediated responses. Thus, salicylates selectively trigger an endoplasmic reticulum stress-responsive signaling pathway initiated through activation of PERK to induce their cellular effects. PMID- 17284448 TI - A role for molecular chaperone Hsc70 in reovirus outer capsid disassembly. AB - After crossing the cellular membrane barrier during cell entry, most animal viruses must undergo further disassembly before initiating viral gene expression. In many cases, these disassembly mechanisms remain poorly defined. For this report, we examined a final step in disassembly of the mammalian reovirus outer capsid: cytoplasmic release of the central, delta fragment of membrane penetration protein mu1 to yield the transcriptionally active viral core particle. An in vitro assay with reticulocyte lysate recapitulated the release of intact delta molecules. Requirements for activity in this system were shown to include a protein factor, ATP, and Mg(2+) and K(+) ions, consistent with involvement of a molecular chaperone such as Hsc70. Immunodepletion of Hsc70 and Hsp70 impaired delta release, which was then rescued by addition of purified Hsc70. Hsc70 was associated with released delta molecules not only in the lysate but also during cell entry. We conclude that Hsc70 plays a defined role in reovirus outer capsid disassembly, during or soon after membrane penetration, to prepare the entering particle for gene expression and replication. PMID- 17284451 TI - Action spectrum of Drosophila cryptochrome. AB - Cryptochromes are a highly conserved class of UV-A/blue light photoreceptors. In Drosophila, cryptochrome is required for the normal entrainment of circadian rhythms to light dark cycles. The photocycle and molecular mechanism of animal cryptochrome photoreception are presently unknown. Drosophila cryptochrome undergoes light-dependent degradation when heterologously expressed in Schneider 2 cells. We have generated Drosophila luciferase-cryptochrome fusion proteins to more precisely monitor light-dependent cryptochrome degradation. We found that the luciferase-cryptochrome fusion protein undergoes light-dependent degradation with luciferase activity declining approximately 50% within 5 min of light exposure and approximately 85% within 1 h of light exposure. Degradation is inhibited by MG-132, consistent with a proteasomal degradation mechanism. Irradiance-response curves yield an action spectrum similar to absorption spectra for prokaryotic and eukaryotic cryptochromes with highest sensitivity in the UV A. A luciferase-cryptochrome fusion protein lacking the terminal 15 amino acids is stably expressed in the dark but demonstrates increased sensitivity to light induced degradation. The conferral of light-dependent degradation on a heterologous protein by fusion to cryptochrome may be a useful tool for probing protein function in cell expression systems. PMID- 17284452 TI - Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct. AB - Alzheimer disease is characterized by the abnormal aggregation of amyloid beta peptide into extracellular fibrillar deposits known as amyloid plaques. Soluble oligomers have been observed at early time points preceding fibril formation, and these oligomers have been implicated as the primary pathological species rather than the mature fibrils. A significant issue that remains to be resolved is whether amyloid oligomers are an obligate intermediate on the pathway to fibril formation or represent an alternate assembly pathway that may or may not lead to fiber formation. To determine whether amyloid beta oligomers are obligate intermediates in the fibrillization pathway, we characterized the mechanism of action of amyloid beta aggregation inhibitors in terms of oligomer and fibril formation. Based on their effects, the small molecules segregated into three distinct classes: compounds that inhibit oligomerization but not fibrillization, compounds that inhibit fibrillization but not oligomerization, and compounds that inhibit both. Several compounds selectively inhibited oligomerization at substoichiometric concentrations relative to amyloid beta monomer, with some active in the low nanomolar range. These results indicate that oligomers are not an obligate intermediate in the fibril formation pathway. In addition, these data suggest that small molecule inhibitors are useful for clarifying the mechanisms underlying protein aggregation and may represent potential therapeutic agents that target fundamental disease mechanisms. PMID- 17284453 TI - Localizing hotspots of antisense transcription. AB - Analysis of the transcriptome by computational and experimental methods has established that sense-antisense transcriptional units are a common phenomenon. Although the regulatory potential of antisense transcripts has been experimentally verified in a number of studies, the biological importance of sense-antisense regulation of gene expression is still a matter of debate. Here, we report the identification of sequence features that are associated with antisense transcription. We show that the sequence composition of the first exon and the 5'end of the first intron of many human genes is similar to the sequence composition observed in promoter regions as measured by the density of known transcription regulatory motifs. Cloned intron-derived fragments were found to possess bidirectional promoter activity. In agreement with the reported abundance of antisense transcripts overlapping the 5'UTR, mapping of the 5'ends of antisense transcripts to the corresponding sense transcripts revealed that the first exon and the 5'end of the first intron are hotspots of antisense transcription as measured by the number of antisense transcription start sites per unit sequence. CpG dinucleotide suppression that is typically weak in non methylated promoter regions is similarly weakened upstream as well as downstream of the first exon. In support of antisense transcripts playing a regulatory role, we find that 5'UTRs and first exons of genes with overlapping antisense transcripts are significantly longer than the genomic average. Interestingly, a similar size distribution of 5'UTRs and first exons is observed for genes silenced by CpG island methylation in human cancer. PMID- 17284454 TI - A rapid reaction analysis of uracil DNA glycosylase indicates an active mechanism of base flipping. AB - Uracil DNA glycosylase (UNG) is the primary enzyme for the removal of uracil from the genome of many organisms. A key question is how the enzyme is able to scan large quantities of DNA in search of aberrant uracil residues. Central to this is the mechanism by which it flips the target nucleotide out of the DNA helix and into the enzyme-active site. Both active and passive mechanisms have been proposed. Here, we report a rapid kinetic analysis using two fluorescent chromophores to temporally resolve DNA binding and base-flipping with DNA substrates of different sequences. This study demonstrates the importance of the protein-DNA interface in the search process and indicates an active mechanism by which UNG glycosylase searches for uracil residues. PMID- 17284455 TI - DISPLAR: an accurate method for predicting DNA-binding sites on protein surfaces. AB - Structural and physical properties of DNA provide important constraints on the binding sites formed on surfaces of DNA-targeting proteins. Characteristics of such binding sites may form the basis for predicting DNA-binding sites from the structures of proteins alone. Such an approach has been successfully developed for predicting protein-protein interface. Here this approach is adapted for predicting DNA-binding sites. We used a representative set of 264 protein-DNA complexes from the Protein Data Bank to analyze characteristics and to train and test a neural network predictor of DNA-binding sites. The input to the predictor consisted of PSI-blast sequence profiles and solvent accessibilities of each surface residue and 14 of its closest neighboring residues. Predicted DNA contacting residues cover 60% of actual DNA-contacting residues and have an accuracy of 76%. This method significantly outperforms previous attempts of DNA binding site predictions. Its application to the prion protein yielded a DNA binding site that is consistent with recent NMR chemical shift perturbation data, suggesting that it can complement experimental techniques in characterizing protein-DNA interfaces. PMID- 17284457 TI - 2'-fluoro-4'-thioarabino-modified oligonucleotides: conformational switches linked to siRNA activity. AB - The synthesis of oligonucleotides containing 2'-deoxy-2'-fluoro-4' thioarabinonucleotides is described. 2'-Deoxy-2'-fluoro-5-methyl-4' thioarabinouridine (4'S-FMAU) was incorporated into 18-mer antisense oligonucleotides (AONs). 4'S-FMAU adopts a predominantly northern sugar conformation. Oligonucleotides containing 4'S-FMAU, unlike those containing FMAU, were unable to elicit E. coli or human RNase H activity, thus corroborating the hypothesis that RNase H prefers duplexes containing oligonucleotides that can adopt eastern conformations in the antisense strand. The duplex structure and stability of these oligonucleotides was also investigated via circular dichroism (CD)- and UV- binding studies. Replacement of the 4'-oxygen by a sulfur atom resulted in a marked decrease in melting temperature of AON:RNA as well as AON:DNA duplexes. 2'-deoxy-2'-fluoro-4'-thioarabinouridine (4'S-FAU) was incorporated into 21-mer small interfering RNA (siRNA) and the resulting siRNA molecules were able to trigger RNA interference with good efficiency. Positional effects were explored, and synergy with 2'F-ANA, which has been previously established as a functional siRNA modification, was demonstrated. PMID- 17284458 TI - Interplay between CRP-cAMP and PII-Ntr systems forms novel regulatory network between carbon metabolism and nitrogen assimilation in Escherichia coli. AB - In Escherichia coli, utilization of carbon sources is regulated by the phosphoenolpyruvate-dependent phosphotransferase system (PTS), which modulates the intracellular levels of cAMP. The cAMP receptor protein (CRP) controls the transcription of many catabolic genes. The availability of nitrogen is sensed by the PII protein at the level of intracellular glutamine. Glutamine is transported mainly by GlnHPQ, and synthesized by glutamine synthetase (GS) encoded by glnA. Previous studies suggest that CRP affects nitrogen assimilation. Here we showed that at least two mechanisms are involved. First, CRP activates glnHp1 via synergistic binding with sigma 70 RNA polymerase (Esigma(70)) and represses glnHp2. As a consequence, in the presence of glutamine, the overall enhancement of glnHPQ expression alters GlnB signalling and de-activates glnAp2. Second, in vitro studies show that CRP can be recruited by sigma 54 holoenzyme (Esigma(54)) to a site centred at -51.5 upstream of glnAp2. CRP-induced DNA-bending prevents the nitrogen regulation protein C (NtrC) activator from approaching the activator accessible face of the promoter-bound Esigma(54) closed complex, and inhibits glnAp2. Therefore, as the major transcriptional effector of the 'glucose effect', CRP affects both the signal transduction pathway and the overall geometry of the transcriptional machinery of components of the nitrogen regulon. PMID- 17284456 TI - The structure and function of small nucleolar ribonucleoproteins. AB - Eukaryotes and archaea use two sets of specialized ribonucleoproteins (RNPs) to carry out sequence-specific methylation and pseudouridylation of RNA, the two most abundant types of modifications of cellular RNAs. In eukaryotes, these protein-RNA complexes localize to the nucleolus and are called small nucleolar RNPs (snoRNPs), while in archaea they are known as small RNPs (sRNP). The C/D class of sno(s)RNPs carries out ribose-2'-O-methylation, while the H/ACA class is responsible for pseudouridylation of their RNA targets. Here, we review the recent advances in the structure, assembly and function of the conserved C/D and H/ACA sno(s)RNPs. Structures of each of the core archaeal sRNP proteins have been determined and their assembly pathways delineated. Furthermore, the recent structure of an H/ACA complex has revealed the organization of a complete sRNP. Combined with current biochemical data, these structures offer insight into the highly homologous eukaryotic snoRNPs. PMID- 17284459 TI - An optimized method for detecting gamma-H2AX in blood cells reveals a significant interindividual variation in the gamma-H2AX response among humans. AB - Phosphorylation of histone H2AX on serine 139 (gamma-H2AX, gammaH2AX) occurs at sites flanking DNA double-strand breaks (DSBs) and can provide a measure of the number of DSBs within a cell. Here we describe a rapid and simple flow-cytometry based method, optimized to measure gamma-H2AX in non-fixed peripheral blood cells. No DSB induced signal was observed in H2AX-/- cells indicating that our FACS method specifically recognized gamma-H2AX accumulation. The gamma-H2AX assay was capable of detecting DNA damage at levels 100-fold below the detection limit of the alkaline comet assay. The gamma-H2AX signal was quantitative with a linear increase of the gamma-H2AX signal over two orders of magnitude. We found that all nucleated blood cell types examined, including the short-lived neutrophils induce gamma-H2AX in response to DSBs. Interindividual difference in the gamma-H2AX signal in response to ionizing radiation and the DSB-inducing drug calicheamicin was almost 2-fold in blood cells from patients, indicating that the amount of gamma-H2AX produced in response to a given dose of radiation varies significantly in the human population. This simple method could be used to monitor response to radiation or DNA-damaging drugs. PMID- 17284460 TI - Deinococcus glutaminyl-tRNA synthetase is a chimer between proteins from an ancient and the modern pathways of aminoacyl-tRNA formation. AB - Glutaminyl-tRNA synthetase from Deinococcus radiodurans possesses a C-terminal extension of 215 residues appending the anticodon-binding domain. This domain constitutes a paralog of the Yqey protein present in various organisms and part of it is present in the C-terminal end of the GatB subunit of GatCAB, a partner of the indirect pathway of Gln-tRNA(Gln) formation. To analyze the peculiarities of the structure-function relationship of this GlnRS related to the Yqey domain, a structure of the protein was solved from crystals diffracting at 2.3 A and a docking model of the synthetase complexed to tRNA(Gln) constructed. The comparison of the modeled complex with the structure of the E. coli complex reveals that all residues of E. coli GlnRS contacting tRNA(Gln) are conserved in D. radiodurans GlnRS, leaving the functional role of the Yqey domain puzzling. Kinetic investigations and tRNA-binding experiments of full length and Yqey truncated GlnRSs reveal that the Yqey domain is involved in tRNA(Gln) recognition. They demonstrate that Yqey plays the role of an affinity-enhancer of GlnRS for tRNA(Gln) acting only in cis. However, the presence of Yqey in free state in organisms lacking GlnRS, suggests that this domain may exert additional cellular functions. PMID- 17284462 TI - Cryptic loxP sites in mammalian genomes: genome-wide distribution and relevance for the efficiency of BAC/PAC recombineering techniques. AB - Cre is widely used for DNA tailoring and, in combination with recombineering techniques, to modify BAC/PAC sequences for generating transgenic animals. However, mammalian genomes contain recombinase recognition sites (cryptic loxP sites) that can promote illegitimate DNA recombination and damage when cells express the Cre recombinase gene. We have created a new bioinformatic tool, FuzznucComparator, which searches for cryptic loxP sites and we have applied it to the analysis of the whole mouse genome. We found that cryptic loxP sites occur frequently and are homogeneously distributed in the genome. Given the mammalian nature of BAC/PAC genomic inserts, we hypothesised that the presence of cryptic loxP sites may affect the ability to grow and modify BAC and PAC clones in E. coli expressing Cre recombinase. We have observed a defect in bacterial growth when some BACs and PACs were transformed into EL350, a DH10B-derived bacterial strain that expresses Cre recombinase under the control of an arabinose-inducible promoter. In this study, we have demonstrated that Cre recombinase expression is leaky in un-induced EL350 cells and that some BAC/PAC sequences contain cryptic loxP sites, which are active and mediate the introduction of single-strand nicks in BAC/PAC genomic inserts. PMID- 17284461 TI - Biochemical and genetic analysis of RNA cap guanine-N2 methyltransferases from Giardia lamblia and Schizosaccharomyces pombe. AB - RNA cap guanine-N2 methyltransferases such as Schizosaccharomyces pombe Tgs1 and Giardia lamblia Tgs2 catalyze methylation of the exocyclic N2 amine of 7 methylguanosine. Here we performed a mutational analysis of Giardia Tgs2, entailing an alanine scan of 17 residues within the minimal active domain. Alanine substitutions at Phe18, Thr40, Asp76, Asn103 and Asp140 reduced methyltransferase specific activity to <3% of wild-type Tgs2, thereby defining these residues as essential. Alanines at Pro142, Tyr148 and Pro185 reduced activity to 7-12% of wild-type. Structure-activity relationships at Phe18, Thr40, Asp76, Asn103, Asp140 and Tyr148, and at three other essential residues defined previously (Asp68, Glu91 and Trp143) were gleaned by testing the effects of 18 conservative substitutions. Our results engender a provisional map of the Tgs2 active site, which we discuss in light of crystal structures of related methyltransferases. A genetic analysis of S. pombe Tgs1 showed that it is nonessential. An S. pombe tgs1Delta strain grows normally, notwithstanding the absence of 2,2,7-trimethylguanosine caps on its U1, U2, U4 and U5 snRNAs. However, we find that S. pombe requires cap guanine-N7 methylation catalyzed by the enzyme Pcm1. Deletion of the pcm1(+) gene was lethal, as were missense mutations in the Pcm1 active site. Thus, whereas m(7)G caps are essential in both S. pombe and S. cerevisiae, m(2,2,7)G caps are not. PMID- 17284465 TI - Respiratory effect of prolonged electrical weapon application on human volunteers. AB - BACKGROUND: Conducted electrical weapons (CEWs) are used by law enforcement to subdue combative subjects. Occasionally, subjects will die after a CEW has been used on them. It is theorized that CEWs may contribute to these deaths by impairing respiration. OBJECTIVES: To examine the respiratory effects of CEWs. METHODS: Human volunteers received a 15-second application of electrical current from a CEW while wearing a respiratory measurement device. Common respiratory parameters were collected before, during, and after exposure. Health histories and demographic information were also collected. RESULTS: Fifty-two subjects were analyzed. Thirty-four underwent a 15-second continuous exposure, and 18 underwent three 5-second burst exposures. In the continuous application group, the baseline mean tidal volume of 1.1 L increased to 1.8 L during application, the baseline end-tidal CO2 level went from 40.5 mm Hg to 37.3 mm Hg after exposure, the baseline end-tidal oxygen level went from 118.7 mm Hg to 121.3 mm Hg after exposure, and the baseline respiratory rate went from 15.9 breaths/min to 16.4 breaths/min after exposure. In the 5-second burst group, the baseline mean tidal volume increased to 1.85 L during application, the baseline end-tidal CO2 level went from 40.9 mm Hg to 39.1 mm Hg after exposure, the baseline end-tidal oxygen level went from 123.1 mm Hg to 127.0 mm Hg after exposure, and the baseline respiratory rate went from 13.8 breaths/min to 14.6 breaths/min after exposure. CONCLUSIONS: Prolonged CEW application did not impair respiratory parameters in this population of volunteers. Further study is recommended to validate these findings in other populations. PMID- 17284463 TI - Translational repression of mouse mu opioid receptor expression via leaky scanning. AB - Mu opioid receptor (MOR) expression is under temporal and spatial controls, but expression levels of the MOR gene are relatively low in vivo. In addition to transcriptional regulations, upstream AUGs (uAUGs) and open reading frames (uORFs) profoundly affect the translation of the primary ORF and thus the protein levels in several genes. The 5'-untranslated region (UTR) of mouse MOR mRNA contains three uORFs preceding the MOR main initiation codon. In MOR-fused EGFP or MOR promoter/luciferase reporter constructs, mutating each uAUG individually or in combinations increased MOR transient heterologous expression in neuroblastoma NMB and HEK293 cells significantly. Translation of such constructs increased up to 3-fold without altering the mRNA levels if either the third uAUG or both the second and third AUGs were mutated. Additionally, these uAUG-mediated translational inhibitions were independent of their peptide as confirmed by internal mutation analyses in each uORF. Translational studies indicated that protein syntheses were initiated at these uAUG initiation sites, with the third uAUG initiating the highest translation level. These results support the hypothesis that uORFs in mouse MOR mRNA act as negative regulators through a ribosome leaky scanning mechanism. Such leaky scanning resulted in the suppression of mouse MOR under normal conditions. PMID- 17284464 TI - DNA supercoiling suppresses real-time PCR: a new approach to the quantification of mitochondrial DNA damage and repair. AB - As a gold standard for quantification of starting amounts of nucleic acids, real time PCR is increasingly used in quantitative analysis of mtDNA copy number in medical research. Using supercoiled plasmid DNA and mtDNA modified both in vitro and in cancer cells, we demonstrated that conformational changes in supercoiled DNA have profound influence on real-time PCR quantification. We showed that real time PCR signal is a positive function of the relaxed forms (open circular and/or linear) rather than the supercoiled form of DNA, and that the conformation transitions mediated by DNA strand breaks are the main basis for sensitive detection of the relaxed DNA. This new finding was then used for sensitive detection of structure-mediated mtDNA damage and repair in stressed cancer cells, and for accurate quantification of total mtDNA copy number when all supercoiled DNA is converted into the relaxed forms using a prior heat-denaturation step. The new approach revealed a dynamic mtDNA response to oxidative stress in prostate cancer cells, which involves not only early structural damage and repair but also sustained copy number reduction induced by hydrogen peroxide. Finally, the supercoiling effect should raise caution in any DNA quantification using real time PCR. PMID- 17284466 TI - The impact of input and output factors on emergency department throughput. AB - OBJECTIVES: To quantify the impact of input and output factors on emergency department (ED) process outcomes while controlling for patient-level variables. METHODS: Using patient- and system-level data from multiple sources, multivariate linear regression models were constructed with length of stay (LOS), wait time, treatment time, and boarding time as dependent variables. The products of the 20th to 80th percentile ranges of the input and output factor variables and their regression coefficients demonstrate the actual impact (in minutes) of each of these factors on throughput outcomes. RESULTS: An increase from the 20th to the 80th percentile in ED arrivals resulted in increases of 42 minutes in wait time, 49 minutes in LOS (admitted patients), and 24 minutes in ED boarding time (admitted patients). For admit percentage (20th to 80th percentile), the increases were 12 minutes in wait time, 15 minutes in LOS, and 1 minute in boarding time. For inpatient bed utilization as of 7 AM (20th to 80th percentile), the increases were 4 minutes in wait time, 19 minutes in LOS, and 16 minutes in boarding time. For admitted patients boarded in the ED as of 7 AM (20th to 80th percentile), the increases were 35 minutes in wait time, 94 minutes in LOS, and 75 minutes in boarding time. CONCLUSIONS: Achieving significant improvement in ED throughput is unlikely without determining the most important factors on process outcomes and taking measures to address variations in ED input and bottlenecks in the ED output stream. PMID- 17284467 TI - Shopping for price in medical care. AB - Insurers are well positioned to support their enrollees in shopping for care because of their ability to analyze complex data--reflecting both their negotiated discounts and the enrollee's benefit structure--should they decide to commit resources to this task. Government transparency initiatives can help those who are uninsured or want to use out-of-network providers with data on prices and all patients by gathering and disseminating data on quality. But clumsy requirements to disclose insurer-provider contracts could lead to higher prices. Greater price transparency might help curb rising costs, but many overstate the likely magnitude of its contribution. PMID- 17284469 TI - GASA4, one of the 14-member Arabidopsis GASA family of small polypeptides, regulates flowering and seed development. AB - Members of the plant-specific gibberellic acid-stimulated Arabidopsis (GASA) gene family play roles in hormone response, defense and development. We have identified six new Arabidopsis GASA genes, bringing the total number of family members to 14. Here we show that these genes all encode small polypeptides that share the common structural features of an N-terminal putative signal sequence, a highly divergent intermediate region and a conserved 60 amino acid C-terminal domain containing 12 conserved cysteine residues. Analysis of promoter::GUS (beta glucuronidase) transgenic plants representing six different GASA loci reveals that the promoters are activated in a variety of stage- and tissue-specific patterns during development, indicating that the GASA genes are involved in diverse processes. Characterization of GASA4 shows that the promoter is active in the shoot apex region, developing flowers and developing embryos. Phenotypic analyses of GASA4 loss-of-function and gain-of-function lines indicate that GASA4 regulates floral meristem identity and also positively affects both seed size and total seed yield. PMID- 17284468 TI - Self-pay markets in health care: consumer Nirvana or caveat emptor? AB - As consumers face more incentives to make cost-conscious medical care decisions, some policymakers cite self-pay markets as models for consumer shopping. An analysis of the LASIK market revealed limited shopping overall, despite the fact that patients pay the full cost. For other self-pay procedures, consumers shop even less, for reasons ranging from urgency, to costs of obtaining price quotes, to quality concerns that prompt many consumers to rely on word-of-mouth recommendations. Given that consumer shopping is not prevalent in most self-pay markets, we expect the extent of shopping to be even more limited for many services covered by insurance. PMID- 17284471 TI - Intra-atrial course of the right coronary artery: a previously missed anomaly. PMID- 17284470 TI - Large-scale analysis of chlorophyll fluorescence kinetics in Synechocystis sp. PCC 6803: identification of the factors involved in the modulation of photosystem stoichiometry. AB - Since chlorophyll fluorescence reflects the redox state of photosynthetic electron transport chain, monitoring of chlorophyll fluorescence has been successfully applied for the screening of photosynthesis-related genes. Here we report that the mutants having a defect in the regulation of photosystem stoichiometry could be identified through the simple comparison of the induction kinetics of chlorophyll fluorescence. We made a library containing 500 mutants in the cyanobacterium Synechocystis sp. PCC 6803 with transposon-mediated gene disruption, and the mutants were used for the measurement of chlorophyll fluorescence kinetics for 45 s. We picked up two genes, pmgA and sll1961, which are involved in the modulation of photosystem stoichiometry. The disruptants of the two genes share common characteristics in their fluorescence kinetics, and we searched for mutants that showed such characteristics. Out of six mutants identified so far, five showed a different photosystem stoichiometry under high light conditions. Thus, categorization based on the similarity of fluorescence kinetics is an excellent way to identify the function of genes. PMID- 17284472 TI - Demonstration of clinically silent plaque rupture by dual-source computed tomography. PMID- 17284473 TI - Teenagers' perceptions of blindness related to smoking: a novel message to a vulnerable group. AB - BACKGROUND: Cigarette smoking often starts in teenage years. It is not known whether teenagers are aware of the association of smoking with eye disease and blindness. AIM: To explore the knowledge of the link between smoking, and eye diseases and blindness, and the likely impact of this knowledge among teenagers in UK. METHODS: A cross-sectional survey, using a structured interview of teenagers attending four organised social events, was conducted. Awareness and fear of blindness, and of three smoking-related diseases (lung cancer, heart disease and stroke) and a distractor condition (deafness) was investigated. The likelihood of smokers quitting on developing early signs of each condition was determined. RESULTS: A 92% "opt in" response rate was achieved. Out of 260 teenagers (16-18 years), 15%, 27% and 81% believed that smoking caused stroke, heart disease and lung cancer, respectively. Only 5% believed smoking caused blindness. Subjects ranked their fear of each of the five conditions, scoring five for the most feared and one for the least feared. Subjects were significantly (p<0.01) more fearful (mean scores in brackets) of blindness (4.2) than of lung cancer (3.4), heart disease (2.3) and deafness (1.2). More teenagers (p<0.01) said they would stop smoking on developing early signs of blindness compared with early signs of lung or heart disease. CONCLUSIONS: Awareness of the risk of blindness from smoking is low among teenagers, but fear of blindness may be more likely to motivate teenagers to stop smoking than fear of lung or heart disease. Teenagers should be made more aware of the ocular risks of cigarette smoking as a novel public health measure. PMID- 17284474 TI - Fear of death and dying. PMID- 17284475 TI - Angiotensin-converting enzyme inhibitor fetopathy: long-term outcome. AB - Fetal exposure to angiotensin-converting enzyme inhibitors (ACEIs) is associated with increased neonatal morbidity and mortality. Long-term follow-up of three patients with fetal ACEI exposure revealed impaired renal function in two, severe hypertension and proteinuria in one and isolated polycythaemia in all three. Careful long-term follow-up of children with ACEI fetopathy is recommended. PMID- 17284476 TI - Relationship of neonatologists' end-of-life decisions to their personal fear of death. AB - OBJECTIVE: To study the relationship of Australian and New Zealand (ANZ) neonatologists' personal fear of death to their forgoing life-sustaining treatment and hastening death in newborns destined for severe disability and newborns for whom further treatment is considered non-beneficial or overly burdensome. DESIGN: A self-report questionnaire survey of ANZ neonatologists. SETTING: Neonatologists registered in the 2004 ANZ Directory of Neonatal Intensive Care Units. PARTICIPANTS: 78 of 138 (56%) neonatologists who responded to the study questionnaire. MAIN OUTCOME MEASURES: Between-group differences in the Multidimensional Fear of Death Scale. RESULTS: In newborns for whom further treatment was deemed futile, 73 neonatologists reported their attitude to hastening death as follows: 23 preferred to hasten death by withdrawing minimal treatment, 35 preferred to hasten death with analgesia-sedation, and 15 reported that hastening death was unacceptable. Analysis of variance showed a statistically significant difference between the three groups regarding fear of the dying process (F = 3.78, p = 0.028), fear of premature death (F = 3.28, p = 0.044) and fear of being destroyed (F = 3.20, p = 0.047). Post hoc comparisons showed that neonatologists who reported that hastening death was unacceptable compared with neonatologists who preferred to hasten death with analgesia sedation had significantly less fear of the dying process and fear of premature death, and significantly more fear of being destroyed. CONCLUSIONS: ANZ neonatologists' personal fear of death and their attitude to hastening death when further treatment is considered futile are significantly related. Neonatologists' fear of death may influence their end-of-life decisions. PMID- 17284477 TI - Role of DNA/chromatin organisation and scavenging capacity in USX- and proton- induced DNA damage. AB - DNA higher-order structures and (non-histonic) *;OH radical scavengers have well known protective effects in the induction of single- and double-strand breaks by ionising radiation. In a previous work, such protective roles have been quantified for gamma radiation (Valota et al., Int. J. Radiat. Biol. 79, 2003). As a starting base for the simulations, we used the PARTRAC Monte Carlo code, developed within a collaboration involving the University of Pavia and the GSF institute. The code can reproduce the track structure of photons, electrons, protons and heavier ions in liquid water, and it can simulate the DNA content of a human cell at different organisation levels, based on an atom-by-atom approach. In this work we extended the calculations to Ultra-Soft X rays (USX) and protons, separately analysing the effects of different radiation types on various DNA structures (i.e. linear DNA, SV40 'minichromosomes' and compact chromatin) as a function of the *OH scavenging capacity (SC). Both for USX and protons, the calculated damage yields decreased by increasing the SC for the three considered target types. Such decrease can be ascribed to the competition between the reactions *OH-DNA and *OH-scavenger, which becomes more and more likely by increasing the SC. Furthermore, linear DNA was found to be more radiosensitive than SV40 'minichromosomes', which in turn were more radiosensitive than compact chromatin, which is protected by histones. Comparisons with experimental data by Fulford et al. (Int. J. Radiat. Biol. 77, 2001) relative to USX irradiation showed very good agreement. The dependence of the modulating role played by DNA organisation and scavenging capacity on radiation quality is presented and discussed. PMID- 17284478 TI - Parental attitudes towards the management of asthma in ethnic minorities. AB - OBJECTIVES: Children from Indian and Pakistani (South Asian) and black minority groups have relatively high rates of attendance at accident and emergency (A&E) departments and admissions to hospital in the UK. We examine parents' beliefs and management of childhood asthma that possibly contribute to their greater use of hospital services. DESIGN: Questionnaire survey. SETTING: Three London hospitals serving multicultural communities with a high proportion of South Asian subjects. PARTICIPANTS: Parent(s) accompanying 150 children aged 3-9 years with asthma attending asthma clinics and A&E departments. MAIN OUTCOME MEASURES: White, South Asian and "other" ethnic group parents were compared regarding their children's symptoms and asthma in relation to why their children had developed asthma, use of asthma treatments, views about the prognosis of their children's asthma, and their feelings associated with stigma. RESULTS: South Asian more often than white parents stated that they did not give preventers to their children (odds ratio (OR) 0.30; 95% confidence interval (CI) 0.12 to 0.75), that most drugs were "addictive" (OR 3.89; 95% CI 1.47 to 10.27), and that medicines could do more harm than good (OR 3.19; 95% CI 1.22 to 8.34). South Asian and "other" ethnic groups were more reluctant to tell others about their children's asthma (OR 0.11; 95% CI 0.01 to 1.06 and OR 0.06; 95% CI 0.01 to 0.65, respectively). CONCLUSION: Cultural perspectives related to ethnicity are key factors in the understanding of asthma management. Health staff should give high priority to eliciting parents' beliefs regarding management of their children's asthma. PMID- 17284479 TI - Adrenocortical suppression increases the risk of relapse in nephrotic syndrome. AB - OBJECTIVE: Children with nephrotic syndrome (NS) are usually treated with long term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic-pituitary-adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis. STUDY DESIGN: To study the risks of HPA suppression, a modified low dose synacthen test (0.5 mug) was administered to 32 patients (22 male,10 female) with a mean age of 9.7 years (range 3.8-17.6 years) with NS receiving long-term alternate day prednisolone for over 12 months. Twelve patients received alternate day prednisolone, 11 alternate prednisolone+levamisole and nine alternate prednisolone+ciclosporin. All patients were followed up for 3 years and the relapse rate noted. RESULTS: 20/32 (62.5%) patients had a peak serum cortisol concentration of <500 nmol/l, which suggested suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the ciclosporin group. During follow-up, the 20 children who had a suboptimal cortisol response had significantly more relapses (95 relapses) compared to the 12 children with a normal cortisol response who had 24 relapses (p = 0.01). CONCLUSIONS: Children with NS receiving long-term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using the modified synacthen test. Children with evidence of HPA suppression are at a greater risk of relapse. PMID- 17284481 TI - Variation in policies for the management of febrile neutropenia in United Kingdom Children's Cancer Study Group centres. AB - OBJECTIVE: To assess the variation in the current UK management strategies for the treatment of febrile neutropenia in childhood. DESIGN AND SETTING: A postal survey of all 21 United Kingdom Children's Cancer Study Group (UKCCSG) centres assessing and collating local policies, protocols or guidelines relating to the management of febrile neutropenia. Further direct contact was undertaken to clarify any uncertainties. RESULTS: All 21 centres provided information. The policies used to manage febrile neutropenia in the centres around the UK vary in almost every aspect of management. Definitions of fever ranged from a persistent temperature of >37.5 degrees C to a single reading of >39 degrees C. Neutropenia was inconsistently defined as an absolute neutrophil count of <1x10(9), <0.75x10(9 )or <0.5x10(9). Choices of antibiotic approaches, empirical modifications and antistaphylococcal treatment were different in each protocol. The use of risk stratification was undertaken in 11 centres, with six using a policy of reduced intensity therapy in low risk cases. Empirical antifungal treatment was very poorly described and varied even more widely. CONCLUSIONS: There was a great deal of variation in definitions and treatment of febrile neutropenia in the UKCCSG children's cancer treatment centres. A degree of variation as a result of local microbiological differences is to be expected, but beyond this we should seek to standardise the core of our approach to defining fever and neutropenia, risk stratification and duration of empirical therapy in a way that maintains safety, minimises resource utilisation and maximises quality of life. PMID- 17284480 TI - Relationship between five common viruses and febrile seizure in children. AB - OBJECTIVES: To examine the role of viruses in febrile seizures (FS) by comparing the relative risk (RR) of developing FS with common viral infections and subsequent risk of recurrence. METHODS: We matched the medical records of all children admitted with FS over 5 years and the contemporary records for all admissions for febrile illnesses associated with influenza, adenovirus, parainfluenza, respiratory syncytial virus (RSV) and rotavirus to calculate the RR of FS following these viral infections. For patients admitted for a first FS, we carried multivariate analysis for type of viral infection, age of onset, family history, complex FS features and maximum temperature during the episode, to identify the risk factors for recurrence. RESULTS: There were 923 admissions for FS, of which 565 were for first seizures. The five most common viruses in FS were influenza (163/923, 17.6%), adenovirus (63/923, 6.8%), parainfluenza (55/923, 6%), RSV (25/923, 2.7%) and rotavirus (12/923, 1.3%). Incidences of FS in febrile illnesses due to these viruses were 20.8% (163/785) for influenza, 20.6% (55/267) for parainfluenza, 18.4% (63/343) for adenovirus, 5.3% (25/468) for RSV and 4.3% (12/280) for rotavirus. Complex FS occurred in 20.6% (n = 191) and the risk of developing complex FS was similar for the five viruses. Overall recurrence rate was 20.5% and was not predicted by type of viral infection. CONCLUSION: The risk of developing FS is similar with influenza, adenovirus or parainfluenza and is higher than with RSV or rotavirus. Type of viral infection is not important in predicting complex features or future recurrences. PMID- 17284482 TI - Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function. AB - 3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function. PMID- 17284483 TI - Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. AB - Embryonic stem (ES) cells are promising for cardiac repair, but directing their differentiation toward cardiomyocytes remains challenging. We investigated whether the heart guides ES cells toward cardiomyocytes in vivo and whether allogeneic ES cells were immunologically tolerated. Undifferentiated mouse ES cells consistently formed cardiac teratomas in nude or immunocompetent syngeneic mice. Cardiac teratomas contained no more cardiomyocytes than hind-limb teratomas, suggesting lack of guided differentiation. ES cells also formed teratomas in infarcted hearts, indicating injury-related signals did not direct cardiac differentiation. Allogeneic ES cells also caused cardiac teratomas, but these were immunologically rejected after several weeks, in association with increased inflammation and up-regulation of class I and II histocompatibility antigens. Fusion between ES cells and cardiomyocytes occurred in vivo, but was rare. Infarct autofluorescence was identified as an artifact that might be mistaken for enhanced GFP expression and true regeneration. Hence, undifferentiated ES cells were not guided toward a cardiomyocyte fate in either normal or infarcted hearts, and there was no evidence for allogeneic immune tolerance of ES cell derivatives. Successful cardiac repair strategies involving ES cells will need to control cardiac differentiation, avoid introducing undifferentiated cells, and will likely require immune modulation to avoid rejection. PMID- 17284485 TI - An 'overwhelming illness': women's experiences of learning to live with chronic fatigue syndrome/myalgic encephalomyelitis. AB - The processes through which people learn to live with CFS/ME are poorly understood and have not been rigorously explored within the literature. Semi structured interviews were conducted with eight women and analysed using interpretative phenomenological analysis. Participants initially described being 'overwhelmed' by CFS/ME. Attempts at seeking help were unsatisfactory and participants described feeling let down and disbelieved. Participants reacted to this by identifying types of 'self-help' and assertively taking more responsibility for their illness and its treatment. Acquiring social support and greater knowledge were key mediating factors in the emergence of control and acceptance. The relevance of the themes to existing research and the implications for clinical practice are considered. PMID- 17284484 TI - 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. AB - MRI has been employed to elucidate the migratory behavior of stem/progenitor cells noninvasively in vivo with traditional proton (1H) imaging of iron oxide nanoparticle-labeled cells. Alternatively, we demonstrate that fluorine (19F) MRI of cells labeled with different types of liquid perfluorocarbon (PFC) nanoparticles produces unique and sensitive cell markers distinct from any tissue background signal. To define the utility for cell tracking, mononuclear cells harvested from human umbilical cord blood were grown under proendothelial conditions and labeled with nanoparticles composed of two distinct PFC cores (perfluorooctylbromide and perfluoro-15-crown-5 ether). The sensitivity for detecting and imaging labeled cells was defined on 11.7T (research) and 1.5T (clinical) scanners. Stem/progenitor cells (CD34+ CD133+ CD31+) readily internalized PFC nanoparticles without aid of adjunctive labeling techniques, and cells remained functional in vivo. PFC-labeled cells exhibited distinct 19F signals and were readily detected after both local and intravenous injection. PFC nanoparticles provide an unequivocal and unique signature for stem/progenitor cells, enable spatial cell localization with 19F MRI, and permit quantification and detection of multiple fluorine signatures via 19F MR spectroscopy. This method should facilitate longitudinal investigation of cellular events in vivo for multiple cell types simultaneously. PMID- 17284486 TI - Critical review: nicotine for the fetus, the infant and the adolescent? AB - The recent expansion of Nicotine Replacement Therapy to pregnant women and children ignores the fact that nicotine impairs, disrupts, duplicates and/or interacts with essential physiological functions and is involved in tobacco related carcinogenesis. The main concerns in the present context are its fetotoxicity and neuroteratogenicity that can cause cognitive, affective and behavioral disorders in children born to mothers exposed to nicotine during pregnancy, and the detrimental effects of nicotine on the growing organism. Hence, the use of nicotine, whose efficacy in treating nicotine addiction is controversial even in adults, must be strictly avoided in pregnancy, breastfeeding, childhood and adolescence. PMID- 17284487 TI - Goal disturbance, cognitive coping and psychological distress in HIV-infected persons. AB - This study aims to explore the relationships between cognitive coping, goal disturbance and psychological distress in HIV-infected persons. A sample of 43 HIV positive persons completed questionnaires that assessed cognitive coping, goal frustration, depressive symptoms and quality of life. Goal frustration and, to a lesser extent, the cognitive coping strategy 'positive reappraisal' were related to psychological distress. Intervention programmes might usefully implement the topics of goal disturbance and positive reappraisal. PMID- 17284488 TI - Detrimental effects of falling on health and well-being in later life: the mediating roles of perceived control and optimism. AB - Falling is common among older adults, often resulting in decreased functional ability and quality of life. To understand processes underlying the fall/health and well-being relationship, it is important to identify psychosocial mediators. The current study examined the impact of falling on subsequent physical health, negative emotions and physical activity among 231 young-old (<85) and old-old (85+) community-dwelling adults, and the mediating effects of global perceived control (PC) and optimism. Regression results indicated that falling predicted poorer physical health, greater negative emotions and less physical activity among old-old but not young-old adults. Falling negatively predicted PC and optimism, which mediated the effects of falling on health and well-being among the old-old group. Findings have implications for enhancing recovery from falling via bolstering PC and optimism. PMID- 17284489 TI - Socioeconomic differences in the effects of prayer on physical symptoms and quality of life. AB - The extent to which religiosity is related to well-being may differ as a function of race/ethnicity, education or income. We asked 155 caregivers to complete measures of religiosity, prayer, physical symptoms and quality of life. Lower education and, to a lesser extent, lower income were correlated with religiosity and prayer. There were few direct relationships of religiosity and prayer with quality of life and health symptoms. However, the relationships became significant when education and, to a lesser degree, income were taken into account. Prayer was associated with fewer health symptoms and better quality of life among less educated caregivers. PMID- 17284490 TI - Identifying key processes of exercise behaviour change associated with movement through the stages of exercise behaviour change. AB - This longitudinal study identified processes of exercise behaviour change (POC) associated with movement between the stages of exercise behaviour change (SOC). Participants' (N = 312) physical activity, SOC and POC were recorded at baseline, one, three, six and 12 months post-test. Following baseline, participants received one of three physical activity interventions. The process of self liberation was important at each stage movement. The process of stimulus control appeared important when progressing from contemplation to preparation. Progression from action into maintenance was associated with increased use of social liberation and helping relationships. The study indicated the transtheoretical model is applicable to a British population. PMID- 17284491 TI - Factorial invariance of the 13-item Sense of Coherence scale across gender. AB - This study examined the gender invariance of the 13-item Sense of Coherence (SOC) scale. Confirmatory factor analyses indicated that a single factor model with one pair of correlated errors fit the data well. Invariance testing indicated that the scale is both congeneric and tau equivalent, meaning that a single latent SOC construct holds equally well for males and females, and that both genders demonstrate an equivalent pattern of factor loadings. There was little evidence in support of latent factor mean equivalence across gender. Explanations for the lack of factor mean equivalence were discussed and recommendations for future research were suggested. PMID- 17284492 TI - Risk and protective factors predictive of sense of coherence during adolescence. AB - This brief report presents a study undertaken to better understand the factors that are related to sense of coherence (SOC) levels among youth. Middle school students (N = 1619) reported on risk and protective factors across ecological domains. Analyses revealed that social support, anger expression, family conflict and neighborhood cohesion were predictors of SOC for both males and females. Community views regarding gang membership was a predictor of SOC only for males, while age was a predictor of SOC only for females. The findings suggest a resiliency and ecological framework may be helpful in understanding SOC in youth. PMID- 17284493 TI - Race/ethnicity, socioeconomic status and the health of pregnant women. AB - We examined how traditional (income, education) and nontraditional (public assistance, material deprivation, subjective social standing) socioeconomic status (SES) indicators were associated with self-rated health, physical functioning, and depression in ethnically diverse pregnant women. Using multiple regression, we estimated the association of race/ethnicity (African American, Latino, Asian/Pacific Islander (PI) and white) and sets of SES measures on each health measure. Education, material deprivation, and subjective social standing were independently associated with all health measures. After adding all SES variables, race/ethnic disparities in depression remained for all minority groups; disparities in self-rated health remained for Asian/Pacific Islanders. Few race/ethnic differences were found in physical functioning. Our results contribute to a small literature on how SES might interact with race/ethnicity in explaining health. PMID- 17284494 TI - A Self-determination Theory approach to the study of body image concerns, self presentation and self-perceptions in a sample of aerobic instructors. AB - This study examined motivational predictors of body image concerns, self presentation and self-perceptions using Self-determination Theory as a guiding framework. Aerobic instructors (N = 149) completed questionnaires measuring general need satisfaction, exercise motivational regulations, body image concerns, social physique anxiety and self-perceptions. Introjected regulation predicted all outcome variables in the expected direction. Intrinsic motivation positively predicted physical self-worth. Further, autonomy need satisfaction negatively predicted body image concerns. Finally, differences existed in need satisfaction, introjected regulation, self-perceptions and social physique anxiety between those at risk of developing eating disorders and those not at risk. The results underline the importance of overall and exercise-specific feelings of self-determination in dealing with body image concerns and low self perceptions of aerobics instructors. PMID- 17284495 TI - Sociodemographic differences in myocardial infarction risk perceptions among people with coronary heart disease. AB - This study examines sociodemographic differences in myocardial infarction (MI) risk perceptions among people with coronary heart disease (CHD) (N = 3130). Two variables for comparative risk perceptions were computed: (1) own risk compared to that of an average person; and (2) own risk compared to that of an average person with CHD. Comparative optimism in MI risk perceptions was common, particularly among men and those with higher education. CHD severity and psychosocial resources mediated these sociodemographic differences. These results suggest challenges for secondary prevention in CHD, particularly regarding psychosocial interventions for communicating risk information and supporting lifestyle adjustments. PMID- 17284496 TI - Chronic illness experiences, clinical markers and living with hepatitis C. AB - This study explores the experiences of people with hepatitis C within two models of chronic illness--illness trajectory and shifting perspectives--and examines the effects of clinical markers of disease in relation to perceived health. The findings show some support for both models and suggest how they can be seen as complementary and inter-related. The social consequences of living with hepatitis C, such as potential social limitations and isolation, were more significant and had greater impact than clinical markers of disease progress and should be emphasized in understandings of transformation experiences in chronic illness. PMID- 17284497 TI - Complexity and team dynamics in multiple intervention programmes: challenges and insights for public health psychology. AB - Psychologists engaged in public health research and intervention will become more involved in multiple intervention programming approaches. Managing innovation and complexity is a challenge when the team members come from different disciplines, organizational cultures and research perspectives. This report captures some of those challenges with a participatory, capacity-building, community-based intervention over research stages. We detail successful and less successful attempts to manage the challenges within changing public health contexts and end with concrete suggestions for teams with mixed intervention and research goals. Insights from this project should inform similar programmes with multi-level, participatory, community-based approaches. PMID- 17284498 TI - Validation of a new scale for measuring Concerns of Women Undergoing Assisted Reproductive Technologies (CART). AB - A new instrument was developed and assessed for internal consistency, validity and test-retest reliability. A total of 151 women undergoing IVF/GIFT in California rated concern levels about anesthesia, surgery, recovery time, side effects, finances, missing work, pain, insufficient information and delivering a healthy baby. Validity was assessed by comparing CART to the Infertility Reaction Scale and Bipolar Profile of Moods States, and reliability was investigated by calculating correlations between repeat CARTs. Factor analysis identified three domains: procedural concerns; missing work; and achieving a successful delivery. CART is a new, valid and reliable instrument, which measures concerns during IVF/GIFT not previously identified by existing instruments. PMID- 17284500 TI - Cloninger's Temperament dimensions, socio-economic and lifestyle factors and metabolic syndrome markers at age 31 years in the Northern Finland Birth Cohort 1966. AB - The aim of this study was to assess the association between temperament and metabolic syndrome markers. Cloninger's Temperament and Character Inventory and clinical examination were carried out in 1997 in the Northern Finland Birth Cohort 1966 (N = 4364 respondents). Novelty seeking was positively associated with waist circumference in both genders. Systolic blood pressure was highest in men with high harm avoidance and low persistence scores and lowest in women with high reward dependence and high persistence scores. Childhood socio-economic status did not confound these associations. Smoking and alcohol consumption were associated with higher novelty seeking. Our results suggest that temperament is associated with metabolic syndrome markers and this association may be partly mediated by lifestyle factors and socio-economic status in adulthood. PMID- 17284501 TI - Linezolid for the treatment of patients with central nervous system infection. AB - OBJECTIVE: To review the available evidence regarding the use of linezolid for the treatment of patients with central nervous system (CNS) infections. DATA SOURCES: Relevant studies were identified through searches of the PubMed, Current Contents, and Cochrane databases (publications archived until October 2006). STUDY SELECTION AND DATA EXTRACTION: Case reports, case series, prospective and retrospective studies, and randomized controlled trials were eligible for inclusion in our review if they evaluated the effectiveness and safety of linezolid for the treatment of patients with CNS infections. DATA SYNTHESIS: In 18 (42.9%) of the 42 relevant cases identified, patients had undergone neurosurgical operations and/or had prosthetic devices. Meningitis was the most common CNS infection, accounting for 20 (47.6%) cases. Other CNS infections included brain abscesses (14; 33.3%), ventriculitis (5; 11.9%), and ventriculo peritoneal shunt infection (3; 7.1%). In the 39 patients in whom the responsible pathogen was isolated, those predominantly responsible for the CNS infections were: penicillin-nonsusceptible Streptococcus pneumoniae (7; 17.9%), vancomycin resistant enterococci (6; 15.4%), Nocardia spp. (5; 12.8%), methicillin-resistant Staphylococcus epidermidis (4; 10.3%), and methicillin-resistant Staphylococcus aureus (3; 7.7%). Of the 42 patients who received linezolid for the treatment of CNS infections, 38 (90.5%) were either cured or showed clinical improvement of the infection. The mean duration of follow-up was 7.2 months; no recurrent CNS infection was reported. CONCLUSIONS: The limited published data suggest that linezolid may be considered for the treatment of patients with CNS infections in cases of failure of previously administered treatment or limited available options. PMID- 17284499 TI - Patient-related factors predicting HIV medication adherence among men and women with alcohol problems. AB - The study explored the relationship between HIV medication adherence and alcohol, cognitive, social and affective factors in 272 persons with alcohol problems. Alcohol and cognitive factors significantly differentiated those who did and did not adhere. Specifically, adherence confidence and number of drinks emerged as subfactors driving the associations to adherence. Among those who were less than perfectly adherent (n = 154), only alcohol factors predicted levels of nonadherence. Cognitive factors play a role in understanding some of the differences between those who do and do not adhere to their HIV medications, but they do not differentiate among levels of nonadherence. PMID- 17284503 TI - Implementation of a weight management pharmaceutical care service. AB - BACKGROUND: Obesity, a national epidemic, is one of the leading causes of preventable morbidity and mortality in the US. Pharmacists can play an integral role in weight management. Offering weight management services provides an opportunity to increase public awareness of pharmaceutical care and attract patients to pharmacy programs. OBJECTIVE: To describe the implementation and evaluate outcomes of a weight management pharmaceutical care service in a stand alone pharmaceutical care center on a college campus. METHODS: A retrospective review of data was conducted on 289 patient charts to evaluate the change in weight, body mass index (BMI), percent body fat, and weight-related health conditions in patients who participated in the Healthy Habits program. RESULTS: The net change (change in values observed from first to last appointment) in weight was a loss of 1021.8 kg. The maximum weight change (change seen from the first appointment to the lowest value obtained during the program) was a loss of 1530.5 kg. These values correspond to a net mean weight loss of 3.6 kg per patient (10% of baseline weight) and a maximum mean weight loss per patient of 5.5 kg (15% of baseline weight). Eighty-three patients were able to decrease their BMI category and 76 patients had a decrease in risk status from baseline. CONCLUSIONS: The Auburn University Pharmaceutical Care Center's Healthy Habits program has been successful in helping patients decrease total body weight, BMI, and risk of weight-related complications. In addition, the program has increased the opportunity to identify other pharmaceutical care needs of patients and help establish the role of pharmacists in the management of obesity. PMID- 17284502 TI - Influence of an interactive computer-based inhaler technique tutorial on patient knowledge and inhaler technique. AB - BACKGROUND: Patient knowledge of correct inhaler technique is essential in the treatment of pulmonary disease. Computer delivery of educational content may augment existing teaching efforts. OBJECTIVE: To determine whether a computer based tutorial on inhaler technique could improve patients' knowledge and ability to correctly demonstrate inhaler technique. METHODS: A total of 34 adults with pulmonary disease and experience using inhalers were randomized into the control or intervention groups. The intervention group viewed the tutorial, after which they demonstrated their inhaler technique and completed an Inhaler Technique Knowledge Test. Control group patients, who did not view the tutorial, were also evaluated on their demonstrated inhaler technique and technique knowledge. Additional information obtained included demographics, illness and treatment history, and patients' use of computers. Lastly, all patients who viewed the tutorial completed a brief questionnaire eliciting tutorial feedback. Control group patients were invited to view the tutorial after other data collection was complete. The 2 principal outcomes were the observed inhaler technique score and the inhaler technique knowledge test score. Comparisons between groups were conducted using Student's t-test and chi(2) test, with a p value less than 0.05 considered statistically significant. RESULTS: Eighteen subjects were enrolled in the computer group; 16 were in the control group. The intervention group demonstrated significantly better inhaler technique, with a mean Observed Inhaler Technique Score of 88.3 +/- 12.3 compared with 67.4 +/- 19.2 for the control group (p = 0.001). The intervention group also scored significantly higher on the Inhaler Technique Knowledge Test, with a score of 80.9 +/- 17.0 versus 67.4 +/- 11.8 for the control group (p = 0.01). Overall, the program appeared acceptable to patients. CONCLUSIONS: Patients in the tutorial group demonstrated better inhaler technique and scored higher on the Inhaler Technique Knowledge Test compared with those in a control group. This tutorial may be a useful educational tool to enhance patient education regarding inhaler technique. PMID- 17284504 TI - Clinical pharmacy: reflections and forecasts. PMID- 17284505 TI - Effects of St. John's wort supplementation on ibuprofen pharmacokinetics. AB - BACKGROUND: St. John's wort is a popular herbal supplement that has been involved in various herb-drug interactions. Experimental findings suggest that the supplement may impact CYP2C9 metabolism. CYP2C9 is responsible for the irreversible metabolism of ibuprofen. OBJECTIVE: To examine the effect of 3 weeks of St. John's wort administration on the stereoselective pharmacokinetics of ibuprofen. METHODS: Eight male subjects participated in this study. The single dose pharmacokinetics of ibuprofen were evaluated before and after 21 days of St. John's wort administration. Plasma ibuprofen concentrations were determined, using a stereoselective, reversed-phase HPLC assay. Model independent methods were used to evaluate the pharmacokinetics of each ibuprofen enantiomer. Data were analyzed by 2 way ANOVA testing and confidence interval testing. RESULTS: S(+)-ibuprofen mean +/- SD AUC and maximum concentration (C(max)) values were 131.6 +/- 26.8 microg x h/mL and 31.8 +/- 7.33 microg/mL, respectively, for control samples and 122.4 +/- 32.9 microg x h/mL and 33.6 +/- 7.83 microg/mL, respectively, after St. John's wort treatment. R(-)-ibuprofen mean AUC and C(max) values were 85.1 +/- 26.6 microg x h/mL and 28.4 +/- 8.72 microg/mL, respectively, for control samples and 87.7 +/- 30.1 microg x h/mL and 30.0 +/- 8.97 microg/mL, respectively, for St. John's wort treatment samples. St. John's wort administration resulted in no significant effects on the C(max) and AUC of either stereoisomer. A 31% decrease in S(+)-ibuprofen mean residence time (p = 0.02) was observed. CONCLUSIONS: St. John's wort administration for 21 days had no apparent clinically important impact on the single-dose pharmacokinetic parameters of S(+)- and R(-)-ibuprofen. Although St. John's wort treatment appears to significantly reduce the mean residence time of S-ibuprofen, no ibuprofen dose adjustments appear warranted when the drug is administered orally with St. John's wort, due to the lack of significant change observed in ibuprofen AUC and C(max) for either enantiomer. PMID- 17284506 TI - Laboratory evaluation of potassium and creatinine among ambulatory patients prescribed spironolactone: are we monitoring for hyperkalemia? AB - BACKGROUND: Serum potassium and creatinine evaluation is recommended in patients prescribed spironolactone, yet the proportion of ambulatory patients chronically dispensed spironolactone receiving evaluation is not well understood. OBJECTIVE: To estimate the rate of potassium and creatinine evaluation and identify factors associated with conducting these tests among ambulatory patients dispensed spironolactone. METHODS: A retrospective cohort study was designed to evaluate patients at 10 health maintenance organizations with ongoing spironolactone dispensing for one year (N = 2257). Potassium and creatinine evaluation were determined from administrative data. Associations between patient characteristics and laboratory testing were assessed, using logistic regression modeling. RESULTS: Serum creatinine and potassium were evaluated in 72.3% of patients during a 13 month period. The likelihood of potassium and creatinine monitoring was greater among patients who were older (OR 1.28; 95% CI 1.17 to 1.41 per decade of life); male (OR 1.25; 95% CI 1.01 to 1.54); had diabetes (OR 1.63; 95% CI 1.31 to 2.03); received concomitant therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (OR 2.23; 95% CI 1.74 to 2.87), potassium supplements (OR 1.96; 95% CI 1.51 to 2.54), or digoxin (OR 2.10 95% CI 1.48 to 2.98); or had more outpatient visits (OR 1.31; 95% CI 1.19 to 1.44). Among patients with heart failure (n = 790), factors associated with the incidence of laboratory testing were diabetes (OR 1.64, 95% CI 1.14 to 2.34), outpatient visits (OR 1.20; 95% CI 1.02 to 1.41), and digoxin therapy (OR 2.26; 95% CI 1.38 to 3.69). CONCLUSIONS: Three-fourths of ambulatory patients dispensed spironolactone receive recommended laboratory evaluation, with monitoring more likely to be completed in patients prescribed concomitant therapy with drugs that increase hyperkalemia risk, older patients, and those with diabetes. PMID- 17284507 TI - Mania after venlafaxine withdrawal in a patient with generalized anxiety disorder. PMID- 17284508 TI - Moxifloxacin and torsade de pointes. AB - OBJECTIVE: To report a case of torsade de pointes in a patient receiving moxifloxacin. CASE SUMMARY: An 87-year-old woman was admitted to the hospital for pneumonia, and antibiotic therapy with intravenous moxifloxacin 400 mg/day was initiated. The patient was noted to have significant QTc interval prolongation 2 hours after administration of moxifloxacin and developed torsade de pointes 8-10 hours after moxifloxacin administration. She was converted back to normal sinus rhythm after a precordial thump. Moxifloxacin was discontinued, and the woman's QTc interval subsequently returned to baseline. DISCUSSION: Torsade de pointes is a life-threatening arrhythmia that has previously been associated with the use of fluoroquinolones. Minimal information is available regarding the risk of torsade de pointes with moxifloxacin. According to the Naranjo probability scale, the episode in this case was probably related to administration of intravenous moxifloxacin. CONCLUSIONS: In patients with underlying risk factors for a prolonged QT interval, the use of moxifloxacin can lengthen the interval further and ultimately trigger episodes of torsade de pointes. Moxifloxacin administration in these patients therefore should be administered and monitored judiciously. PMID- 17284509 TI - Pyridostigmine in the treatment of orthostatic intolerance. AB - OBJECTIVE: To review the efficacy of pyridostigmine bromide for the treatment of orthostatic intolerance. DATA SOURCES: MEDLINE and International Pharmaceutical Abstracts were searched (1966-December 2006) using the terms pyridostigmine, acetylcholinesterase inhibitor, orthostatic intolerance, orthostatic hypotension, neurogenic orthostatic hypotension, postural tachycardia syndrome, tachycardia, and orthostatic tachycardia. STUDY SELECTION AND DATA EXTRACTION: Pertinent English-language human clinical trials, case reports, and background material were evaluated for safety and efficacy data. The references of reviewed articles were reviewed and used to identify additional sources. DATA SYNTHESIS: Pyridostigmine bromide has been associated with improved baroreceptor sensitivity and presents a novel approach to treatment of orthostatic intolerance. Four single-dose trials and a follow-up survey encompassing a total of 106 patients were identified. One open-label and one placebo-controlled single-dose trial in patients with neurogenic orthostatic hypotension (NOH) found statistically significant improvement in standing diastolic blood pressures (DBP). Absolute improvements in standing DBP were 3.7 and 6.4 mm Hg in the open-label and controlled trials, respectively. Long-term data consist of a single survey of patients receiving open-label pyridostigmine bromide. Twenty-nine percent of patients who initiated maintenance pyridostigmine bromide discontinued therapy. Concomitant NOH medications were taken by 75% of patients, and 85% of patients reported receiving benefit from pyridostigmine bromide. When evaluated for postural tachycardia syndrome, pyridostigmine bromide significantly reduced standing heart rate (10%). Pyridostigmine bromide significantly reduced symptom scores when compared with baseline but not placebo. The majority of patients included in these trials did not have supine hypertension. CONCLUSIONS: Single doses of pyridostigmine bromide produced modest but statistically significant improvements in hemodynamic measurements. At this time, long-term data are insufficient to support recommending the routine use of pyridostigmine bromide for treatment of orthostatic intolerance. PMID- 17284510 TI - Absence of effect of oral rifaximin on the pharmacokinetics of ethinyl estradiol/norgestimate in healthy females. AB - BACKGROUND: Rifaximin is an oral rifampin analog, and its activity is targeted within the gastrointestinal tract. Some analogs induce the cytochrome P450 family of oxidative enzymes. Ethinyl estradiol (EE), commonly found in oral contraceptives (OCs), is a known CYP3A4 substrate. OBJECTIVE: To determine the potential effect of rifaximin on EE and norgestimate pharmacokinetics. METHODS: In an open-label, crossover study, healthy females received a single dose of OC (EE 0.07 mg/norgestimate 0.50 mg). Following a 1 week washout period, individuals received rifaximin 200 mg every 8 hours for 3 days, with a single dose of OC administered with the ninth rifaximin dose. During both treatment periods, blood samples were collected periodically for up to 96 hours after each OC dose. Plasma concentration-time profiles and pharmacokinetic parameters were characterized for EE and 2 major metabolites of norgestimate, norgestrel (NG) and 17-deacetyl norgestimate (17-DNGM). A drug-drug interaction was confirmed if the 90% CI for the 2 treatment period comparison was outside the 80-125% limit. RESULTS: Twenty six of 28 women completed the study. No differences in pharmacokinetic parameters were observed for EE, NG, or 17-DNGM when a single dose of the OC was administered alone or with rifaximin. In addition, the 90% CI for the bioavailability contrasts (OC alone vs OC with rifaximin) for the maximum plasma concentration, area under the plasma concentration-time curve from zero to the last measurable plasma concentration or to infinity for EE, NG, and 17-DNGM all ranged from 86-118%. These intervals were within the predefined range for equivalence; therefore, no interaction was observed between OC and rifaximin. Rifaximin was well tolerated. CONCLUSIONS: Administration of a 3 day dosing regimen of oral rifaximin was well tolerated and did not alter the pharmacokinetics of a commonly used combination OC containing EE and norgestimate. PMID- 17284511 TI - Immune-related disease before and after vasectomy: an epidemiological database study. AB - BACKGROUND: Vasectomy can be followed by an autoimmune-antibody response. We aimed to determine whether men with immune-related diseases were more or less likely than others to have a vasectomy and then to determine whether vasectomy is associated with the subsequent development of immune-related diseases. METHODS: A database of linked records of hospital statistics was analysed. By comparing a population of men who underwent vasectomy with a reference population, we calculated the rate ratios for selected immune-related diseases before and after vasectomy. RESULTS: Some diseases studied (e.g. asthma and diabetes mellitus) were a little less common, prior to operation, in the vasectomy group than in the reference group. Others were not different. The mean period of follow-up was 13 years. We found no long-term elevation of risk following vasectomy of asthma, diabetes mellitus, ankylosing spondylitis, thyrotoxicosis, multiple sclerosis, myasthenia gravis, inflammatory bowel disease, rheumatoid arthritis or testicular atrophy. There was a short-term elevation of risk of orchitis/epididymitis. CONCLUSIONS: In this large study, with many years of follow-up, we found no evidence that vasectomy increases the subsequent long-term risk of immune-related diseases. PMID- 17284512 TI - Polymorphism of the follistatin gene in polycystic ovary syndrome. AB - Follistatin has been reported as a candidate gene for polycystic ovary syndrome (PCOS) from linkage and association studies. Acting to regulate the development of ovarian follicles and as an antagonist to aromatase activity, alterations in follistatin function or expression may result in key features of PCOS such as reduced serum FSH, impaired ovarian follicle development and augmented ovarian androgen production. We investigated polymorphisms in the FST gene to determine if genetic variation is associated with susceptibility to PCOS or key phenotypic features of PCOS patients in a case-control association study. One hundred and seventy-three PCOS patients of Caucasian descent (mean age 30.0 +/- 4.8 years), conforming to the NIH diagnostic criteria, were recruited from a clinical practice database and 107 normal ovulating women (mean age 38.8 +/- 13.4 years) were recruited from the general community as control subjects. Morphometric data, biochemistry and genomic DNA were collected from study subjects and genotyping was performed on seven Single nucleotide polymorphisms (SNPs) in the FST gene region. Allele frequencies of the SNPs were rs1423560 G/C (0.99/0.01), rs3797297 C/A (0.80/0.20), rs11745088 C/G (0.98/0.02), rs3203788 A/T (0.98/0.02) and rs1062809 G/C (1.00/-), rs1127760 A/T (0.98/0.02) and rs1127761 A/T (0.98/0.02), and these were not significantly different between the PCOS and control groups (P < 0.05). Statistical analysis revealed significant associations between the SNP rs3797297 and sex hormone-binding globulin (P = 0.04) and free androgen index (FAI) (P < 0.01). We conclude that FST is not a susceptibility locus for PCOS; however, the SNP rs3797297 from FST gene was associated with androgenic markers for PCOS and may be of importance in the hyperandrogenaemia of the disease. PMID- 17284513 TI - The loneliness of the expert witness. General Medical Council v. Meadow. PMID- 17284514 TI - Rectal acetaminophen does not reduce morphine consumption after major surgery in young infants. AB - BACKGROUND: The safety and value of acetaminophen (paracetamol) in addition to continuous morphine infusion has never been studied in newborns and young infants. We investigated the addition of acetaminophen to evaluate whether it decreased morphine consumption in this age group after major thoracic (non cardiac) or abdominal surgery. METHODS: A randomized controlled trial was performed in 71 patients given either acetaminophen 90-100 mg kg(-1) day(-1)or placebo rectally, in addition to a morphine loading dose of 100 microg kg(-1) and 5-10 microg kg(-1) h(-1) continuous infusion. Analgesic efficacy was assessed using Visual Analogue Scale (VAS) and COMFORT scores. Extra morphine was administered if VAS was > or = 4. RESULTS: We analysed data of 54 patients, of whom 29 received acetaminophen and 25 received placebo. Median (25-75th percentile) age was 0 (0-2) months. Additional morphine bolus requirements and increases in continuous morphine infusion were similar in both groups (P = 0.366 and P = 0.06, respectively). There was no significant difference in total morphine consumption, respectively, 7.91 (6.59-14.02) and 7.19 (5.45-12.06) mug kg(-1) h(-1) for the acetaminophen and placebo group (P = 0.60). COMFORT [median (25-75th percentile) acetaminophen 10 (9-12) and placebo 11 (9-13)] and VAS [median (25-75th percentile) acetaminophen 0.0 (0.0-0.2) and placebo 0.0 (0.0 0.3)] scores did not differ between acetaminophen and placebo group (P = 0.06 and P = 0.73, respectively). CONCLUSIONS: Acetaminophen, as an adjuvant to continuous morphine infusion, does not have an additional analgesic effect and should not be considered as standard of care in young infants, 0-2 months of age, after major thoracic (non-cardiac) or abdominal surgery. PMID- 17284515 TI - Suprabasal Dsg2 expression in transgenic mouse skin confers a hyperproliferative and apoptosis-resistant phenotype to keratinocytes. AB - Desmoglein 2 (Dsg2), a component of the desmosomal cell-cell adhesion structure, has been linked to invasion and metastasis in squamous cell carcinomas. However, it is unknown whether--and if so how--Dsg2 contributes to the malignant phenotype of keratinocytes. In this study, we addressed the consequences of Dsg2 overexpression under control of the involucrin promoter (Inv-Dsg2) in the epidermis of transgenic mice. These mice exhibited epidermal hyperkeratosis with slightly disrupted early and late differentiation markers, but intact epidermal barrier function. However, Inv-Dsg2 transgene expression was associated with extensive epidermal hyperplasia and increased keratinocyte proliferation in basal and suprabasal epidermal strata. Cultured Inv-Dsg2 keratinocytes showed enhanced cell survival in the anchorage-independent state that was critically dependent on EGF receptor activation and NF-kappaB activity. Consistent with the hyperproliferative and apoptosis-resistant phenotype of Inv-Dsg2 transgenic keratinocytes, we observed enhanced activation of multiple growth and survival pathways, including PI 3-kinase/AKT, MEK-MAPK, STAT3 and NF-kappaB, in the transgenic skin in situ. Finally, Inv-Dsg2 transgenic mice developed intraepidermal skin lesions resembling precancerous papillomas and were more susceptible to chemically induced carcinogenesis. In summary, overexpression of Dsg2 in epidermal keratinocytes deregulates multiple signaling pathways associated with increased growth rate, anchorage-independent cell survival, and the development of skin tumors in vivo. PMID- 17284516 TI - LAP2alpha-binding protein LINT-25 is a novel chromatin-associated protein involved in cell cycle exit. AB - Lamina-associated polypeptide 2alpha (LAP2alpha) is a nuclear protein dynamically associating with chromatin during the cell cycle. In addition, LAP2alpha interacts with A-type lamins and retinoblastoma protein and regulates cell cycle progression via the E2F-Rb pathway. Using yeast two-hybrid analysis and three independent in vitro binding assays we identified a new LAP2alpha interaction partner of hitherto unknown functions, which we termed LINT-25. LINT-25 protein levels were upregulated during G1 phase in proliferating cells and upon cell cycle exit in quiescence, senescence and differentiation. Upon cell cycle exit LINT-25 accumulated in heterochromatin foci, and LAP2alpha protein levels were downregulated by proteasomal degradation. Although LAP2alpha was not required for the upregulation and reorganization of LINT-25 during cell cycle exit, transient expression of LINT-25 in proliferating cells caused loss of LAP2alpha and subsequent cell death. Our data show a role of LINT-25 and LAP2alpha during cell cycle exit, in which LINT-25 acts upstream of LAP2alpha. PMID- 17284517 TI - Wound-induced ATP release and EGF receptor activation in epithelial cells. AB - We have shown previously that wounding of human corneal epithelial (HCE) cells resulted in epidermal growth factor receptor (EGFR) transactivation through ectodomain shedding of heparin-binding EGF-like growth factor (HB-EGF). However, the initial signal to trigger these signaling events in response to cell injury remains elusive. In the present study, we investigated the role of ATP released from the injured cells in EGFR transactivation in HCE cells as well as in BEAS 2B cells, a bronchial epithelial cell line. Wounding of epithelial monolayer resulted in the release of ATP into the culture medium. The wound-induced rapid activation of phosphatidylinositol-3-kinase (PI3K) and extracellular signal regulated kinase (ERK) pathways in HCE cells was attenuated by eliminating extracellular ATP, ADP and adenosine. The nonhydrolyzable ATP analog ATP-gamma-S induced rapid and sustained EGFR activation that depended on HB-EGF shedding and ADAM (a disintegrin and metalloproteinase). Targeting pathways leading to HB-EGF shedding and EGFR activation attenuated ATP-gamma-S-enhanced closure of small scratch wounds. The purinoceptor antagonist reactive blue 2 decreased wound closure and attenuated ATP-gamma-S induced HB-EGF shedding. Taken together, our data suggest that ATP, released upon epithelial injury, acts as an early signal to trigger cell responses including an increase in HB-EGF shedding, subsequent EGFR transactivation and its downstream signaling, resulting in wound healing. PMID- 17284518 TI - EHD1 regulates beta1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration. AB - beta1 integrins bind to the extracellular matrix and stimulate signaling pathways leading to crucial cellular functions, including proliferation, apoptosis, cell spreading and migration. Consequently, control of beta1 integrin function depends upon its subcellular localization, and recent studies have begun to unravel the complex regulatory mechanisms involved in integrin trafficking. We report that the C-terminal Eps15-homology (EH) domain-containing protein EHD1 plays an important role in regulating beta1 integrin transport. Initially, we demonstrated that RNAi-knockdown of Ehd1 results in impaired recycling of beta1 integrins and their accumulation in a transferrin-containing endocytic recycling compartment. Mouse embryonic fibroblast (MEF) cells derived from EHD1-knockout mice (Ehd1(-/-) MEF) exhibited lower overall levels of beta1 integrins on the plasma membrane, but higher cell-surface-expressed activated beta1 integrins, and larger, more prominent focal adhesions resulting from slower kinetics of focal adhesion disassembly. In addition, both migration and cell spreading on fibronectin were impaired in Ehd1(-/-) MEF cells, and these defects could be similarly induced by EHD1-RNAi treatment of normal Ehd1(+/+) MEF cells. They could also be rescued by transfection of wild-type EHD1 into Ehd1(-/-) MEF cells. Our data support a role for EHD1 in beta1 integrin recycling, and demonstrate a requirement for EHD1 in integrin-mediated downstream functions. PMID- 17284519 TI - A large complex containing Patched and Smoothened initiates Hedgehog signaling in Drosophila. AB - Hedgehog acts as an organizer during development. Its signaling involves the receptor Patched, signal transducer Smoothened and a cytoplasmic complex containing the transcription factor Cubitus interruptus tethered to the Smoothened carboxyl tail. Without Hedgehog, Patched represses Smoothened resulting in proteolysis of Cubitus interruptus to its repressor form. With Hedgehog, Patched repression of Smoothened is relieved and Cubitus interruptus is activated. Sex-lethal, the master switch for sex determination in Drosophila, has been shown to associate with Cubitus interruptus and the cytoplasmic components of the Hedgehog signaling pathway. Additionally, Sex-lethal responds to the presence of Hedgehog in a Patched-dependent manner. The latter prompted us to examine the role of Patched in signaling. We find that Cubitus interruptus, Sex lethal, Patched and Smoothened co-immunoprecipitate and co-fractionate, suggesting a large complex of both membrane and cytoplasmic components of the Hedgehog pathway. The entire complex is present at the plasma membrane and the association of Patched changes depending on the activation state of the pathway; it also is not female specific. Colocalization analyses suggest that Sex-lethal alters the endocytic cycling of the Hedgehog components and may augment the Hedgehog signal in females by decreasing the proteolytic cleavage of Cubitus interruptus, availing more of it for activation. PMID- 17284520 TI - Tau impacts on growth-factor-stimulated actin remodeling. AB - The microtubule-associated protein tau interacts with the SH3 domain of non receptor Src family protein tyrosine kinases. A potential consequence of the SH3 interaction is the upregulation of tyrosine kinase activity. Here we investigated the activation of Src or Fyn by tau, both in vitro and in vivo. Tau increased the kinase activity in in vitro assays and in transfected COS7 cells. In platelet derived growth factor (PDGF)-stimulated fibroblasts, tau appeared to prime Src for activation following PDGF stimulation, as reflected by changes in Src mediated actin rearrangements. In addition, while fibroblasts normally recovered actin stress fibers by 5-7 hours after PDGF stimulation, tau-expressing cells showed sustained actin breakdown. Microtubule association by tau was not required for the observed changes in actin morphology. Inhibition of Src kinases or a mutant deficient in Src interaction reduced the effects, implicating Src family protein tyrosine kinases as a mediator of the effects of tau on actin rearrangements. Our results provide evidence that the interaction of tau with Src upregulates tyrosine kinase activity and that this interaction allows tau to impact on growth-factor-induced actin remodeling. PMID- 17284521 TI - Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death. AB - The pro-inflammatory cytokine interleukin-1beta is a key mediator of inflammation and is implicated in the pathogenesis of diverse disease states. Despite its biological importance, the mechanisms of its processing to an active form and its trafficking to the extracellular compartment remain poorly understood. Interleukin-1beta secretion is proposed to occur via several distinct mechanisms including microvesicle shedding and the regulated secretion of lysosomes. In this study, we report for the first time that caspase-1-dependent processing of pro interleukin-1beta can occur in the cytosol following activation of P2X7-receptor. We also provide evidence that the pathway of secretion in this model is independent of the lysosomal trafficking regulator, a protein involved in lysosome secretion. Although release of interleukin-1beta occurred before the appearance of significant levels of lactate dehydrogenase in the supernatant, the cells ultimately died. It is clear that structural changes preceding cell death, occurring after caspase-1 activation, promote the cellular release of interleukin 1beta. We investigated the involvement of lipid rafts in this process and discovered that depleting the plasma membrane of cholesterol did not adversely affect interleukin-1beta secretion in response to ATP. We propose that, in macrophages, ATP-induced interleukin-1beta processing occurs in the cytosol by a mechanism that resembles pyroptosis. PMID- 17284522 TI - PI-3-kinase-dependent membrane recruitment of centaurin-alpha2 is essential for its effect on ARF6-mediated actin cytoskeleton reorganisation. AB - GTPase activating proteins (GAPs) of the centaurin family regulate the actin cytoskeleton and vesicle trafficking through inactivation of the ADP-ribosylation factor (ARF) family of small GTP-binding proteins. We report the functional characterisation of centaurin-alpha(2), which is structurally related to the centaurin-alpha(1) ARF6 GAP. centaurin-alpha(2) contains an N-terminal GAP domain followed by two pleckstrin homology (PH) domains (N-PH and C-PH). In vitro, GFP centaurin-alpha(2) specifically binds the phosphatidylinositol (PI) 3-kinase lipid products, PI 3,4-P(2) and PI 3,4,5-P(3) (PIP(3)), through its C-terminal PH domain. In agreement with this observation, GFP-centaurin-alpha(2) was recruited to the plasma membrane from the cytosol in EGF-stimulated cells in a PI-3-kinase dependent manner. Moreover, the C-PH domain is sufficient and necessary for membrane recruitment of centaurin-alpha(2). centaurin-alpha(2) shows sustained kinetics of PI-3-kinase-mediated membrane recruitment in EGF-stimulated cells, owing to its binding to PI 3,4-P(2). centaurin-alpha(2) prevents ARF6 translocation to, and cortical actin formation at, the plasma membrane, which are phenotypic indications for ARF6 activation in EGF-stimulated cells. Moreover, the constitutively active mutant of ARF6 reverses the effect of centaurin-alpha(2) on cortical actin formation. The membrane targeted centaurin-alpha(2) is constitutively active. Together, these studies indicate that centaurin-alpha(2) is recruited in a sustained manner to the plasma membrane through binding to PI 3,4-P(2) and thereby regulates actin reorganisation via ARF6. PMID- 17284523 TI - Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age. AB - Rates of autophagy, the mechanism responsible for lysosomal clearance of cellular components, decrease with age. We have previously described an age-related decline in chaperone-mediated autophagy (CMA), a selective form of autophagy, by which particular cytosolic proteins are delivered to lysosomes after binding to the lysosome-associated membrane protein type 2A (LAMP-2A), a receptor for this pathway. Rates of CMA decrease with age because of a decrease in the levels of LAMP-2A. In this work we have investigated the reasons for the reduced levels of LAMP-2A with age. While transcriptional rates of LAMP-2A remain unchanged with age, the dynamics and stability of the receptor in the lysosomal compartment are altered. The mobilization of the lysosomal lumenal LAMP-2A to the membrane when CMA is activated is altered in lysosomes from old animals, leading to the presence of an unstable pool of lumenal LAMP-2A. By contrast, the regulated cleavage of LAMP-2A at the lysosomal membrane is reduced owing to altered association of the receptor and the protease responsible for its cleavage to particular membrane microdomain regions. We conclude that age-related changes at the lysosomal membrane are responsible for the altered turnover of the CMA receptor in old organisms and the consequent decline in this pathway. PMID- 17284524 TI - CLLU1 expression analysis adds prognostic information to risk prediction in chronic lymphocytic leukemia. AB - We recently identified a disease-specific gene CLLU1 in chronic lymphocytic leukemia (CLL) and also demonstrated that high CLLU1 expression levels predict poor clinical outcome. To validate this finding, we measured CLLU1 mRNA expression levels by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 175 patients with CLL. Analyses of IgV(H) mutational status, ZAP-70 expression, CD38 expression, and chromosomal aberrations were also performed. High levels of CLLU1 expression were associated with shorter overall survival (P < .001), with a 7% increase in risk of early death by each doubling of the CLLU1 expression level. Stratification for age at diagnosis demonstrated a strong prognostic significance of CLLU1 expression in patients younger than 70 years (P < .001), but not in patients aged 70 or older (P = .61). The prognostic significance of IgV(H) mutational status and ZAP-70 expression had a similar age dependent variation. Multivariate analysis in the younger age group showed that CLLU1 expression analysis added further prognostic information within all prognostic subgroups, with the exception of patients with unmutated IgV(H) CLL. Only CLLU1 expression and IgV(H) mutational status had independent predictive power. Thus, analysis of CLLU1 expression is highly applicable in risk prediction in CLL for patients of an age eligible for risk stratification. PMID- 17284525 TI - DC-HIL is a negative regulator of T lymphocyte activation. AB - T-cell activation is the net product of competing positive and negative signals transduced by regulatory molecules on antigen-presenting cells (APCs) binding to corresponding ligands on T cells. Having previously identified DC-HIL as a receptor expressed by APCs that contains an extracellular immunoglobulin (Ig) like domain, we postulated that it plays a role in T-cell activation. To probe this function, we created soluble recombinant DC-HIL, which we observed to bind activated (but not resting) T cells, indicating that expression of the putative ligand on T cells is induced by activation. Binding of DC-HIL to naive T cells attenuated these cells' primary response to anti-CD3 antibody, curtailing IL-2 production, and preventing entry into the cell cycle. DC-HIL also inhibited reactivation of T cells previously activated by APCs (secondary response). By contrast, addition of soluble DC-HIL to either allogeneic or ovalbumin-specific lymphocyte reactions augmented T-cell proliferation, and its injection into mice during the elicitation (but not sensitization) phase of contact hypersensitivity exacerbated ear-swelling responses. Mutant analyses showed the inhibitory function of DC-HIL to reside in its extracellular Ig-like domain. We conclude that endogenous DC-HIL is a negative regulator of T lymphocyte activation, and that this native inhibitory function can be blocked by exogenous DC-HIL, leading to enhanced immune responses. PMID- 17284526 TI - Racial variation in the relationship of anemia with mortality and mobility disability among older adults. AB - Anemia is more common among older blacks than older whites. However, it is unclear whether anemia predicts adverse events similarly in both races. Data on 1018 black and 1583 white adults aged 71 to 82 years were analyzed. Anemia, as defined by World Health Organization (WHO) criteria, was used to predict mortality over 6 years and incidence of mobility disability over 4 years. In proportional hazards models of mortality in whites, the age-adjusted hazard ratio (HR) for anemia in men was 1.96 (95% confidence interval [CI]: 1.35, 2.83) and in women was 2.86 (95% CI: 1.69, 4.82). In contrast, anemia was not associated with mortality in black men (HR = 1.15 [95% CI: 0.77, 1.72]) or women (HR = 1.39 [95% CI: 0.91, 2.14]). Higher mortality rate was observed only in black men with hemoglobin values more than 20 g/L (2.0 g/dL) below the WHO cutoff, whereas mortality rates were elevated in white men with hemoglobin values 1 to 10, 11 to 20, and more than 20 g/L below the WHO cutoff. In conclusion, anemia was significantly associated with increased risk of death and mobility disability in community-dwelling older whites. Conversely, older blacks classified as anemic by WHO criteria were not at risk for adverse events, indicating that alternative criteria are warranted. PMID- 17284527 TI - The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. AB - The molecular alterations underlying the pathogenesis of angioimmunoblastic T cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell- and follicular dendritic cell-related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (T(FH)) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published T(FH)-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several T(FH) genes was validated by immunohistochemistry in AITLs. A few cases with molecular T(FH)-like features were identified among CD30(-) PTCLs-u. Our findings strongly support that T(FH) cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30(-) PTCLs-u may derive from or be related to AITL. PMID- 17284528 TI - Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia. AB - Waldenstrom macroglobulinemia (WM) is an incurable lymphoplasmacytic lymphoma with limited options of therapy. Protein kinase Cbeta (PKCbeta) regulates cell survival and growth in many B-cell malignancies. In this study, we demonstrate up regulation of PKCbeta protein in WM using protein array techniques and immunohistochemistry. Enzastaurin, a PKCbeta inhibitor, blocked PKCbeta activity and induced a significant decrease of proliferation at 48 hours in WM cell lines (IC(50), 2.5-10 muM). Similar effects were demonstrated in primary CD19(+) WM cells, without cytotoxicity on peripheral blood mononuclear cells. In addition, enzastaurin overcame tumor cell growth induced by coculture of WM cells with bone marrow stromal cells. Enzastaurin induced dose-dependent apoptosis at 48 hours mediated via induction of caspase-3, caspase-8, caspase-9, and PARP cleavage. Enzastaurin inhibited Akt phosphorylation and Akt kinase activity, as well as downstream p-MARCKS and ribosomal p-S6. Furthermore, enzastaurin demonstrated additive cytotoxicity in combination with bortezomib, and synergistic cytotoxicity in combination with fludarabine. Finally, in an in vivo xenograft model of human WM, significant inhibition of tumor growth was observed in the enzastaurin-treated mice (P = .028). Our studies therefore show that enzastaurin has significant antitumor activity in WM both in vitro and in vivo, providing the framework for clinical trials to improve patient outcome in WM. PMID- 17284529 TI - Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria. AB - Deficiency of glycosylphosphatidylinositol (GPI)-anchored molecules on blood cells accounts for most features of paroxysmal nocturnal hemoglobinuria (PNH) but not for the expansion of PNH (GPI(-)) clone(s). A plausible model is that PNH clones expand by escaping negative selection exerted by autoreactive T cells against normal (GPI(+)) hematopoiesis. By a systematic analysis of T-cell receptor beta (TCR-beta) clonotypes of the CD8+ CD57+ T-cell population, frequently deranged in PNH, we show recurrent clonotypes in PNH patients but not in healthy controls: 11 of 16 patients shared at least 1 of 5 clonotypes, and a set of closely related clonotypes was present in 9 patients. The presence of T cell clones bearing a set of highly homologous TCR-beta molecules in most patients with hemolytic PNH is consistent with an immune process driven by the same (or similar) antigen(s)-probably a nonpeptide antigen, because patients sharing clonotypes do not all share identical HLA alleles. These data confirm that CD8+ CD57+ T cells play a role in PNH pathogenesis and provide strong new support to the hypothesis that the expansion of the GPI(-) blood cell population in PNH is due to selective damage to normal hematopoiesis mediated by an autoimmune attack against a nonpeptide antigen(s) that could be the GPI anchor itself. PMID- 17284530 TI - p53 status dictates responses of B lymphomas to monotherapy with proteasome inhibitors. AB - The proapoptotic function of p53 is thought to underlie most anticancer modalities and is also activated in response to oncogenic insults, such as overexpression of the Myc oncoprotein. Here we generated tractable B lymphomas using retroviral transduction of the MYC oncogene into hematopoietic cells with 2 knock-in alleles encoding a fusion between p53 and 4-hydroxytamoxifen (4OHT) receptor (p53ER(TAM)). In these polyclonal tumors, Myc is the only oncogenic lesion, and p53ER(TAM) status can be rapidly toggled between "off" and "on" with 4OHT, provided that the Trp53 promoter has been independently activated. Although 4OHT can trigger widespread apoptosis and overt tumor regression even in the absence of DNA-damaging agents, in tumors with high levels of Mdm2 these responses are blunted. However, cotreatment with proteasome inhibitors fully restores therapeutic effects in vivo. Similarly, human Burkitt lymphomas with wild-type p53 and overexpression of Hdm2 are highly sensitive to proteasome inhibitors, unless p53 levels are reduced using the HPV-E6 ubiquitin ligase. Therefore, proteasome inhibitors could be highly effective as a monotherapy against Myc-induced lymphomas, with no need for adjuvant chemotherapy or radiation therapy. On the other hand, their efficacy is crucially dependent on the wild-type p53 status of the tumor, placing important restrictions on patient selection. PMID- 17284531 TI - Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. AB - The purpose of this study was to characterize a large group of infants with complete DiGeorge anomaly and to evaluate the ability of thymus transplantation to reconstitute immune function in these infants. DiGeorge anomaly is characterized by varying defects of the heart, thymus, and parathyroid glands. Complete DiGeorge anomaly refers to the subgroup that is athymic (< 1%). The characteristics of 54 subjects at presentation and results from 44 consecutive thymus transplantations are reported. Remarkably, only 52% had 22q11 hemizygosity and only 57% had congenital heart disease requiring surgery. Thirty-one percent developed an atypical phenotype with rash and lymphadenopathy. To date, 33 of 44 subjects who received a transplant survive (75%) with post-transplantation follow up as long as 13 years. All deaths occurred within 12 months of transplantation. All 25 subjects who were tested 1 year after transplantation had developed polyclonal T-cell repertoires and proliferative responses to mitogens. Adverse events developing after transplantation included hypothyroidism in 5 subjects and enteritis in 1 subject. In summary, diagnosis of complete DiGeorge anomaly is challenging because of the variability of presentation. Thymus transplantation was well tolerated and resulted in stable immunoreconstitution in these infants. PMID- 17284533 TI - Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. AB - Aberrant micro RNA (miRNA) expression has been described in human malignancies including B-cell lymphomas. We here report BCR-ABL- and c-MYC-dependent regulation of miRNA expression in chronic myeloid leukemia (CML) using microarray analysis (miCHIP) and miRNA-specific quantitative real-time reverse transcriptase polymerase chain reaction (miR-qRT-PCR). In 3 bcr-abl-positive cell lines, expression of miRNAs encoded within the polycistronic miR-17-92 cluster is specifically down-regulated (2- to 5-fold) by both imatinib treatment and anti BCR-ABL RNA interference (RNAi). In addition, anti-c-MYC RNAi reduces miR-17-92 expression in K562 cells in which miRNAs can specifically repress reporter gene expression, as demonstrated by specific miRNA inhibition with antagomirs. Furthermore, lentivirus-mediated overexpression of polycistronic miRNAs in K562 cells confers increased proliferation, partial resistance against anti-c-MYC RNAi, and enhanced sensitivity to imatinib-induced cell death. Finally, we determined miR-17-92 expression in purified normal (n = 4), early chronic-phase (CP) (n = 24), and blast-crisis (BC) (n = 7) CML CD34(+) cells and found up regulation of polycistronic pri-miRNA transcripts in CML and mature miRNAs in CP but not in BC CML. These data are in accordance with a BCR-ABL-c-MYC-miR-17-92 pathway that mediates enhanced miRNA expression in CP but not BC CML CD34(+) cells. Altered miRNA expression may contribute to the pathophysiology of the disease and may provide potential targets for therapeutic intervention. PMID- 17284532 TI - Adoptive transfer of tumor-primed, in vitro-activated, CD4+ T effector cells (TEs) combined with CD8+ TEs provides intratumoral TE proliferation and synergistic antitumor response. AB - The importance of CD4+ Th1 cells during the effector phase of the antitumor response has been overshadowed by emphasis on CD8+ cytotoxic T lymphocytes (CTLs). To determine their respective functions, we purified antigen-primed T cells from tumor-draining lymph nodes and separately activated CD4+ and CD8+ subsets in vitro. Adoptive transfer of CD4+ T effector cells (T(E)s) combined with CD8+ T(E)s provided synergistic therapy for mice bearing subcutaneous, intracranial, or advanced pulmonary metastases. CD4+ T(E)s augmented IFN-gamma production by CD8+ T(E)s when cells were stimulated by tumor digest-containing antigen-presenting cells (APCs). CD4+ T(E)s infiltrated and proliferated extensively in pulmonary tumors, while also stimulating tumor antigen-specific CD8+ T cells. By contrast, CD8+ T(E)s showed minimal intratumoral proliferation in the absence of CD4+ cells or when systemically transferred CD4+ cells were prevented from infiltrating pulmonary tumors by pretreatment with pertussis toxin. Irradiation of CD4+ T cells immediately prior to adoptive transfer abrogated their intratumoral proliferation and direct antitumor efficacy but did not block their capacity to stimulate intratumoral CD8+ T(E) proliferation or tumor regression. These results highlight the importance of cross-presentation of tumor antigens during the effector phase of immunotherapy and suggest that approaches to stimulate CD4+ T(E) function and boost APC cross-presentation within tumors will augment cancer immunotherapy. PMID- 17284534 TI - BMP4, SCF, and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors. AB - The erythroid response to acute anemia relies on the rapid expansion in the spleen of a specialized population of erythroid progenitors termed stress BFU-E. This expansion requires BMP4/Madh5-dependent signaling in vivo; however, in vitro, BMP4 alone cannot recapitulate the expansion of stress BFU-E observed in vivo, which suggests that other signals are required. In this report we show that mutation of the Kit receptor results in a severe defect in the expansion of stress BFU-E, indicating a role for the Kit/SCF signaling pathway in stress erythropoiesis. In vitro analysis showed that BMP4 and SCF are necessary for the expansion of stress BFU-E, but only when spleen cells were cultured in BMP4 + SCF at low-oxygen concentrations did we recapitulate the expansion of stress BFU-E observed in vivo. Culturing spleen cells in BMP4, SCF under hypoxic conditions resulted in the preferential expansion of erythroid progenitors characterized by the expression of Kit, CD71, and TER119. This expression pattern is also seen in stress erythroid progenitors isolated from patients with sickle cell anemia and patients with beta-thalassemia. Taken together these data demonstrate that SCF and hypoxia synergize with BMP4 to promote the expansion and differentiation of stress BFU-E during the recovery from acute anemia. PMID- 17284536 TI - Imatinib concentrations in human milk. PMID- 17284537 TI - IMP-4 and OXA beta-lactamases in Acinetobacter baumannii from Singapore. AB - OBJECTIVE: To compare the incidence of carbapenemase genes in Acinetobacter baumannii between two time periods. METHODS: We studied 114 isolates of imipenem resistant A. baumannii collected over two 5 month periods (in 1996 and 2001). Isolates showing carbapenemase activity by plate bioassay were screened for carbapenemase genes using PCR. Chromosomal DNA from strains carrying carbapenemase genes was subjected to PFGE after digestion with ApaI. RESULTS: The incidence of imipenem-resistant A. baumannii in our hospital rose from 1.1 per 1000 admissions in 1996 to 2.3 per 1000 admissions in 2001. However, the number of carbapenemase-producing A. baumannii rose only slightly in 2001 (0.8 per 1000 admissions) compared to 1996 (0.5 per 1000 admissions). Of 44 isolates with carbapenemase activity, 4 isolates carried bla(IMP-4), 5 carried bla(OXA-58), and 40 carried bla(OXA-23). In addition, most isolates carried a bla(OXA-51)-type beta-lactamase gene. All strains with bla(IMP-4), also carried bla(OXA-58) and bla(PSE-1), but not bla(OXA-51)-type beta-lactamase genes. PCR analysis repeated on seven recent isolates of susceptible A. baumannii showed only the presence of bla(OXA-51)-type beta-lactamase genes. A total of five novel bla(OXA-51)-type beta-lactamase genes (bla(OXA-88),-91,-93,-94, and -95) and one new bla(OXA-58) type beta-lactamase gene (bla(OXA-96)) were found. CONCLUSIONS: The incidence of carbapenemase genes did not vary significantly between the two study periods. There is a wide diversity of OXA genes in A. baumannii in Singapore. The most common carbapenemase gene found in our study was bla(OXA-23). PMID- 17284538 TI - Emergence of blaGES-5 in clinical colistin-only-sensitive (COS) Pseudomonas aeruginosa strain in Brazil. PMID- 17284535 TI - The p21Waf1 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein AML1-ETO. AB - The 8;21 translocation is a major contributor to acute myeloid leukemia (AML) of the M2 classification occurring in approximately 40% of these cases. Multiple mouse models using this fusion protein demonstrate that AML1-ETO requires secondary mutagenic events to promote leukemogenesis. Here, we show that the negative cell cycle regulator p21(WAF1) gene is up-regulated by AML1-ETO at the protein, RNA, and promoter levels. Retroviral transduction and hematopoietic cell transplantation experiments with p21(WAF1)-deficient cells show that AML1-ETO is able to promote leukemogenesis in the absence of p21(WAF1). Thus, loss of p21(WAF1) facilitates AML1-ETO-induced leukemogenesis, suggesting that mutagenic events in the p21(WAF1) pathway to bypass the growth inhibitory effect from AML1 ETO-induced p21(WAF1) expression can be a significant factor in AML1-ETO associated acute myeloid leukemia. PMID- 17284539 TI - First detection of plasmid-mediated quinolone resistance (qnrA and qnrS) in Escherichia coli strains isolated from humans in Scandinavia. PMID- 17284540 TI - Direct detection of vanB2 using the Roche LightCycler vanA/B detection assay to indicate vancomycin-resistant enterococcal carriage--sensitive but not specific. PMID- 17284541 TI - Measuring socioeconomic position in health research. AB - OBJECTIVE: In this article we review different measures of socioeconomic position (SEP) and their uses in health-related research. AREAS OF AGREEMENT: Socioeconomic circumstances influence health. AREAS OF CONTROVERSY: Generally, poorer socioeconomic circumstances lead to poorer health. This has generated a search for generic mechanisms that could explain such a general association. However, we propose that there is a greater variation in the association between SEP and health than is generally acknowledged when specific health outcomes are investigated. We propose that studying these variations provide a better understanding of the aetiological mechanisms relating specific diseases with specific exposures. AREAS TO DEVELOP RESEARCH: Using different indicators of SEP in health research can better capture these variations and is important when evaluating the full contribution of confounding by socioeconomic conditions. We propose that using an array of SEP indicators within a life course framework also offers considerable opportunity to explore causal pathways in disease aetiology. PMID- 17284542 TI - Are joints affected by gout also affected by osteoarthritis? AB - OBJECTIVES: To determine whether joints affected by gout are also affected by osteoarthritis (OA). METHODS: A postal questionnaire was sent to all adults aged over 30 years registered with two general practices. The questionnaire assessed a history of gout (doctor diagnosed, or episodes suggestive of acute crystal synovitis) and medication use. Patients who possibly had gout attended for clinical assessment to verify the diagnosis on clinical grounds and assess the distribution of joints affected by acute attacks of gout and OA. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated between the history of an acute attack of gout and the presence of OA at an individual joint adjusted for age, gender, body mass index and prior diuretic use in a binary logistic regression model. RESULTS: A total of 4249 completed questionnaires were returned (32%). From 359 attendees, 164 cases of gout were clinically confirmed. A highly significant association existed between the site of acute attacks of gout and the presence of OA (aOR 7.94; 95% CI 6.27, 10.05). Analysis at individual joint sites revealed a significant association at the first metatarsophalangeal joint (aOR 2.06; 95% CI 1.28, 3.30), mid-foot (aOR 2.85; 95% CI 1.34, 6.03), knee (aOR 3.07; 95% CI 1.05, 8.96) and distal interphalangeal joints (aOR 12.67; 95% CI 1.46, 109.91). CONCLUSION: Acute attacks of gout at individual joint sites are associated with the presence of clinically assessed OA at that joint suggesting that OA may predispose to the localised deposition of monosodium urate crystals. PMID- 17284545 TI - Determinants of satisfaction with community reintegration in older adults with chronic stroke: role of balance self-efficacy. AB - BACKGROUND AND PURPOSE: Many people with stroke have a low level of satisfaction with community reintegration. Although previous studies focused on the effect of physical factors on community reintegration, the effect of psychological factors, such as balance self-efficacy, has been ignored. The purpose of this study was to determine the contribution of balance self-efficacy to satisfaction with community reintegration in older adults with chronic stroke. SUBJECTS: A sample of 63 community-dwelling older adults (50 years of age or older) with chronic stroke (onset of 1 year or more) participated in this study. METHODS: This study involved a secondary analysis of data collected from a stroke exercise clinical trial. Satisfaction with community reintegration was measured with the Reintegration to Normal Living (RNL) Index, and balance self-efficacy was measured with the Activities-specific Balance Confidence (ABC) Scale. RESULTS: Bivariate correlation analyses showed that the RNL Index scores were moderately correlated with the ABC Scale scores. In a multiple regression analysis, after adjusting for age, sex, depression, and other impairments after stroke, balance self-efficacy remained independently associated with the RNL Index scores, accounting for 6.5% of the variance in the RNL Index scores. DISCUSSION AND CONCLUSION: Balance self-efficacy is an independent predictor of satisfaction with community reintegration in older adults with chronic stroke. Improving balance self-efficacy may be instrumental in enhancing community reintegration in this population. PMID- 17284544 TI - Safety of measles, mumps and rubella vaccination in juvenile idiopathic arthritis. AB - OBJECTIVE: To assess the effect of measles, mumps and rubella (MMR) vaccination on disease activity in children with juvenile idiopathic arthritis (JIA). METHODS: A retrospective observational multicentre cohort study was performed in 314 patients with JIA, born between 1989 and 1996. Disease activity and medication use were compared during the period of 6 months before vaccination versus 6 months after vaccination. Disease activity was measured by joint counts, the Physician's global assessment scale and erythrocyte sedimentation rate. Next, we compared disease activity in patients vaccinated between 8 and 9 years of age with the activity in patients who had not been vaccinated at this time (who received MMR between the ages of 9 and 10 years). RESULTS: No increase in disease activity or medication use was seen in the 6 months after MMR vaccination (n = 207), including in patients using methotrexate (n = 49). No overt measles infections were noted. When disease activity in vaccinated patients (n = 108) was compared with activity in those not yet vaccinated (n = 86), there were no significant differences. CONCLUSIONS: The MMR booster vaccination does not seem to aggravate disease activity in JIA. This indicates that the most patients with JIA can be vaccinated safely with the MMR vaccine. A prospective study is recommended. PMID- 17284543 TI - The H63D variant in the HFE gene predisposes to arthralgia, chondrocalcinosis and osteoarthritis. AB - OBJECTIVES: To investigate the relation between the HFE C282Y and H63D variants with arthralgia and joint pathology in the population-based Rotterdam Study. METHODS: From a cohort of 7983 people aged 55 years and over, 2095 randomly drawn subjects were genotyped for C282Y and H63D variants. We compared the frequency of arthralgia, and the presence of chondrocalcinosis, osteophytes, joint space narrowing and radiographic osteoarthritis in hand, hip and knee joints, and Heberden's nodes in carriers of HFE variants with that in non-carriers. RESULTS: Overall, there was a significantly higher frequency of arthralgia (odds ratio 1.6; 95% CI 1.0 to 2.6), oligoarthralgia (2.3; 1.2 to 4.4) and Heberden's nodes (2.0; 1.1 to 3.8) in H63D homozygotes compared with non-carriers. In subjects aged 65 years or younger, H63D homozygotes had significantly more often polyarthralgia (3.1; 1.3 to 7.4), chondrocalcinosis in hip or knee joints (4.7; 1.2 to 18.5), and more hand joints with osteophytes (6.1+/-1.0 vs 4.4+/-0.3), space narrowing (2.8+/-0.5 vs 1.0+/-0.1), radiographic osteoarthritis (4.4+/-0.7 vs 2.0+/-0.2) and Heberden's nodes (3.1; 1.3 to 12.8) than non-carriers. We found no relation of arthralgia or joint pathology to C282Y, but compound heterozygotes had a significantly higher frequency of arthralgia (2.9; 1.0 to 9.3), chondrocalcinosis in hip joints (6.5; 1.8 to 22.3), and an increased number of osteophytes in knee (6.9+/-1.2, n = 5 vs 2.4+/-0.1) joints at a later age (>65 years). CONCLUSIONS: The HFE H63D variant may explain, at least in part, the prevalence of arthralgia in multiple joints sites, chondrocalcinosis, and hand osteoarthritis in the general population. PMID- 17284547 TI - Administration and management skills needed by physical therapist graduates in 2010: a national survey. AB - BACKGROUND AND PURPOSE: Administration and management (A and M) skills are essential to physical therapist practice. This study identified which A and M skills will be most critical for future Doctor of Physical Therapy (DPT) graduates to possess upon entry into clinical practice. SUBJECTS AND METHODS: Using a 7-point scale, 435 randomly selected American Physical Therapy Association members (physical therapists) rated 121 A and M skills based on expectation of the level of independence required by a new DPT graduate. RESULTS: No differences among respondents based on role, work setting, or experience were found, so the data were combined for factor analyses, producing 16 A and M skill groups. The most independence was expected in skills related to self-management, compliance with rules, ethical behavior, and insurance coding. Skills requiring the most assistance were marketing and strategic planning, financial analysis and budgeting, and environmental assessment. DISCUSSION AND CONCLUSION: This study has identified the level of independence for the A and M skills needed by new DPT graduates, provided empirical evidence suggesting which A and M skills should be included in DPT curricula, and suggested a pattern of A and M skill acquisition that applies first to the new therapist and the patient, then to the organization, and finally to the health care environment. PMID- 17284546 TI - A pilot study of the effects of high-intensity aerobic exercise versus passive interventions on pain, disability, psychological strain, and serum cortisol concentrations in people with chronic low back pain. AB - BACKGROUND AND PURPOSE: Given the complex nature of chronic pain, the effects of high-intensity aerobic exercise on pain, disability, psychological strain, and serum cortisol concentrations in people with chronic low back pain were investigated. SUBJECTS: Twenty subjects receiving primary health care were randomly allocated into exercise and control groups. METHODS: Subjects in the exercise group received a 12-week, high-intensity aerobic exercise program. Subjects in the control group received 12 weeks of passive modalities without any form of physical activity. RESULTS: Data analysis identified reductions in pain (41%, t(10)=8.51, P<.001), disability (31%, t(10)=7.32, P<.001), and psychological strain (35%, t(10)=7.09, P<.001) in subjects in the exercise group and no changes in subjects in the control group. High-intensity exercise failed to influence serum cortisol concentrations. DISCUSSION AND CONCLUSION: Regular high-intensity aerobic exercise alleviated pain, disability, and psychological strain in subjects with chronic low back pain but did not improve serum cortisol concentrations. PMID- 17284549 TI - Assessing assessments of decision-making capacity: a few legal queries and commentary on "assessment of decision-making capacity in older adults". PMID- 17284548 TI - Training-induced strength and functional adaptations after hip fracture. AB - BACKGROUND AND PURPOSE: At 3 months after hip fracture, most people are discharged from physical therapy despite residual muscle weakness and overall decreased functional capabilities. The purposes of this study were: (1) to determine, in frail elderly adults after hip fracture and repair, whether a supervised 6-month exercise program would result in strength gains in the fractured limb equivalent to the level of strength in the nonfractured limb; (2) to determine whether the principle of specificity of training would apply to this population of adults; and (3) to determine the relationship between progressive resistance exercise training (PRT) intensity and changes in measures of strength and physical function. SUBJECTS: The study participants were 31 older adults (9 men and 22 women; age [X+/-SD], 79+/-6 years) who had surgical repair of a hip fracture that was completed less than 16 weeks before study enrollment and who completed at least 30 sessions of a supervised exercise intervention. METHODS: Participants completed 3 months of light resistance and flexibility exercises followed by 3 months of PRT. Tests of strength and function were completed at baseline, before PRT, and after PRT. RESULTS: After PRT, the subjects increased knee extension and leg press 1-repetition maximum by 72%+/-56% and 37%+/-30%, respectively. After 3 and 6 months of training, lower-extremity peak torques all increased. Specificity of training appeared to apply only to the nonfractured limb after PRT. Strong correlations were observed between training intensity and lower-extremity strength gains as well as improvements in measures of physical function. DISCUSSION AND CONCLUSION: Frail elderly adults after hip fracture can benefit by extending their rehabilitation in a supervised exercise setting, working at high intensities in order to optimize gains in strength and physical function. PMID- 17284551 TI - Hopes for an empirical base for clinical practice--commentary on "assessment of decision-making capacity in older adults". PMID- 17284550 TI - Contexts of capacity: local and state variations in capacity assessment- commentary on "assessment of decision-making capacity in older adults". PMID- 17284552 TI - Empirical studies of capacity in older adults: finding clarity amidst complexity. PMID- 17284553 TI - Concordance of self-report and informant assessment of emotional well-being in nursing home residents with dementia. AB - The emotional well-being of persons with dementia is an aspect of their quality of life. We examined the stability of informant-rated and self-reported emotion, and the influence of mental status and physical dependence on ratings; we modeled concordance between ratings at both the within- and between-person levels of analysis. We used multilevel modeling to examine data collected over 12 days from 31 nursing home residents. We found significant within-person variation in both informant-rated and self-reported emotion, such that between 40% and 60% of the overall variance in each occurred within persons. We found little correspondence between or within persons between ratings of the informants and residents, regardless of mental status. We recommend statistical techniques that describe these high levels of daily variation in persons with dementia. PMID- 17284554 TI - Feelings of Usefulness to Others, Disability, and Mortality in Older Adults: the MacArthur Study of Successful Aging. AB - We examined feelings of usefulness to others as a predictor of disability and mortality risk in a sample of older adults (aged 70-79 years) from the MacArthur Study of Successful Aging. We examined participants' perceptions of their usefulness to friends and family, measured at a baseline interview, as a predictor of subsequent increases in self-reported mobility disability, the onset of difficulty in performing activities of daily living, or mortality occurrence over a 7-year follow-up period. Compared with older adults who frequently felt useful to others, those who never or rarely felt useful were more likely to experience an increase in disability or to die over the 7-year period, even when we accounted for a number of demographic, health status, behavioral, and psychosocial factors. This suggests that feelings of usefulness may shape health trajectories in older adults. PMID- 17284555 TI - Assessment of decision-making capacity in older adults: an emerging area of practice and research. AB - The convergence of the aging of our society, the increase in blended families, and an enormous intergenerational transfer of wealth has greatly expanded the incidence and importance of capacity assessment of older adults. In this article we discuss the emergence of capacity assessment as a distinct field of study. We review research efforts in two domains: medical decision-making capacity and financial capacity. Existing research in these two areas provides a first pass at many key questions related to capacity assessment, but additional studies that replicate, extend, and improve on this research are urgently needed. An agenda for future is detailed that recommends studies of a wide range of capacity constructs, focusing on clinical markers of diminished capacity, methods to improve clinical assessment, and the many intersections of law and clinical practice. PMID- 17284556 TI - Resilience and transitions from dementia caregiving. AB - Longitudinal studies have documented how dementia caregivers adapt to their role. Less is known about how resilience (defined as lower or higher perceived burden in the face of frequent care demands) affects key dementia caregiving outcomes. The present study utilized data from 1,979 dementia caregivers over a 3-year period to ascertain whether resilience influences transitions from dementia caregiving, such as institutionalization, care recipient death, or loss to follow up. Multinomial logistic regression models revealed that high baseline resilience (low burden, high care demands) was associated with less frequent institutionalization and loss to follow-up as well as more frequent care recipient mortality. The findings suggest the need for researchers to capture the heterogeneity of caregiver resilience when examining the longitudinal implications of informal long-term care and delivering clinical interventions. PMID- 17284557 TI - Cognitive training gain as a predictor of mental status. AB - We examined the association of proximal and distal training gain to subsequent mental status ratings in 302 participants (M = 76.62 years) trained on inductive reasoning or spatial orientation in the Seattle Longitudinal Study. Only training effects on reasoning ability were predictive of mental status group membership. Participants subsequently rated as probably demented did not significantly differ from nondemented participants in magnitude of reasoning training gain 14 years prior to assessment, but they did 7 years prior to status ratings. Proximal training gain 1 year prior to assessment was 0.40 SD for nondemented participants, compared with 0.25 and 0.10 SD for at-risk and probably demented participants, respectively. The combination of reasoning ability training and increased proximal training gain on reasoning ability was associated with a decreased likelihood of being rated as probably demented. PMID- 17284558 TI - Age differences in emotion recognition skills and the visual scanning of emotion faces. AB - Research suggests that a person's emotion recognition declines with advancing years. We examined whether or not this age-related decline was attributable to a tendency to overlook emotion information in the eyes. In Experiment 1, younger adults were significantly better than older adults at inferring emotions from full faces and eyes, though not from mouths. Using an eye tracker in Experiment 2, we found young adults, in comparison with older adults, to have superior emotion recognition performance and to look proportionately more to eyes than mouths. However, although better emotion recognition performance was significantly correlated with more eye looking in younger adults, the same was not true in older adults. We discuss these results in terms of brain changes with age. PMID- 17284559 TI - Age differences in everyday problem-solving effectiveness: older adults select more effective strategies for interpersonal problems. AB - Using the Everyday Problem Solving Inventory of Cornelius and Caspi, we examined differences in problem-solving strategy endorsement and effectiveness in two domains of everyday functioning (instrumental or interpersonal, and a mixture of the two domains) and for four strategies (avoidance-denial, passive dependence, planful problem solving, and cognitive analysis). Consistent with past research, our research showed that older adults were more problem focused than young adults in their approach to solving instrumental problems, whereas older adults selected more avoidant-denial strategies than young adults when solving interpersonal problems. Overall, older adults were also more effective than young adults when solving everyday problems, in particular for interpersonal problems. PMID- 17284560 TI - Feeling better? Trends in general health status. AB - OBJECTIVES: We addressed three questions: Have recent improvements in old-age disability been mirrored in changes in self-reported general health status? Are general health status trends similar for younger and older Americans? Have changes in general health status been uniform across demographic and socioeconomic groups? METHODS: Using logistic regression, we analyzed data from the 1982-2003 National Health Interview Surveys (n = 1,445,872 aged 18-69; n = 178,384 aged 70 and older). RESULTS: The proportion of people aged 70 and older reporting disability declined at 1.38% per year and the proportion 70 and older reporting poor/fair health declined at 1.85% per year. There was less of a decline in reports of poor/fair health at younger ages. Trends for the 18-69 population showed widening health disparities by income but narrowing of the race/ethnicity and education gaps. In the older population, there was no change for those aged 80-84 and 85 and older, the race/ethnicity gap persisted, and both education and income differentials widened over time. DISCUSSION: Declines in proportions reporting poor/fair health among the older population in recent decades mirror declines in disability. Although the younger population has not experienced such progress, its prevalence of poor/fair health is low throughout the 21-year analysis period. Of concern are the growing socioeconomic disparities in health for both younger and older populations. PMID- 17284561 TI - Is gerontology interdisciplinary? PMID- 17284562 TI - Self-rated health trajectories and mortality among older adults. AB - OBJECTIVES: For this article, we evaluated whether measures of prior self-rated health (SRH) trajectories had associations with subsequent mortality that were independent of current SRH assessment and other covariates. METHODS: We used multivariable logistic regression that incorporated four waves of interview data (1993, 1995, 1998, and 2000) from the Asset and Health Dynamics Among the Oldest Old Survey in order to predict mortality during 2000-2002. We defined prior SRH trajectories for each individual based on the slope estimated from a simple linear regression of their own SRH between 1993 and 1998 and the variance around that slope. In addition to SRH reported in 2000, other covariates included in the mortality models reflected health status, health-related behaviors, and individual resources. RESULTS: Among the 3,129 respondents in the analytic sample, SRH in 2000 was significantly (p <.0001) associated with mortality, but the measures of prior SRH trajectories were not. Prior SRH trajectory was, however, a significant determinant of current SRH. We observed significant independent associations with mortality for age, sex, education, lung disease, and having ever smoked. DISCUSSION: Although measures of prior SRH trajectories did not have significant direct associations with mortality, they did have important indirect effects via their influence on current SRH. PMID- 17284563 TI - Age and decline in role-specific feelings of control. AB - OBJECTIVES: The purpose of this study was to see if feelings of control over highly valued social roles decline across late life. I also made an effort to see if two types of social support explained age-related decline in control. METHODS: Harris Interactive of New York conducted interviews with a nationwide longitudinal sample of older adults. Survey questions assessed feelings of control over the most highly valued role, anticipated support (i.e., the belief that support will be forthcoming if needed), and enacted support. RESULTS: The data suggested that feelings of control over the most highly valued role tend to decline across late life. The results also revealed that anticipated support is associated with a stronger sense of control over time, but I observed this relationship only through age 75. Beyond that point, anticipated support was less helpful. In contrast, enacted support did not appear to help older people maintain a strong sense of role-specific control at any age. DISCUSSION: Current research has largely been concerned with age-related change in feelings of control over life as a whole. The findings from this study suggest that it may also be helpful to consider control over the most highly valued role while studying this process. PMID- 17284564 TI - Trends in rates of onset of and recovery from disability at older ages: 1982 1994. AB - OBJECTIVES: Although there is substantial evidence of declining prevalence of disability among the older population during the late 1980s and 1990s, evidence on trends in the underlying dynamics of disability is lacking. For this study, we estimated models of transitions between discrete disability and vital states that incorporated simple linear time trends. METHODS: We analyzed data from the 1982 1994 interviews of the New Haven Established Populations for Epidemiologic Studies of the Elderly study and used three alternative measures of disability status. We estimated separate models of disability prevalence and disability transitions by gender. RESULTS: Eleven of 12 estimated trends in transition rates were statistically significant. For men and women, and for three alternative disability indicators, we found downward trends in rates of both onset of and recovery from disability among people aged 75 and older. We did not find any consistent pattern of trends in disability among those aging into the 75 and older group during this period. DISCUSSION: Our findings are consistent with declining population-level disability prevalence only if any downward trend in onset outweighs the downward trend in recovery. These findings are also consistent with a trend toward more severe disability problems among the disabled population. PMID- 17284565 TI - Functional limitations and changes in levels of depression among older adults: a multiple-hierarchy stratification perspective. AB - OBJECTIVES: This study examined the effects of functional limitations on changes in levels of depression over time. A multiple-hierarchy stratification perspective framed the analyses of potential stratification-based contingencies of race, gender, and socioeconomic status. METHODS: We derived data from a longitudinal study of adults aged 65 and older in the Washington, DC, metropolitan area over a 3-year period (2001-2003). We used ordinary least squares regression models in order to assess the focal associations across a set of social status interaction terms. RESULTS: Changes in functional limitations were associated with changes in depression, but the patterns depended on interactions among race, gender, and socioeconomic status. DISCUSSION: These observations contribute to research by blending ideas from double and triple jeopardy and differential vulnerability perspectives. Although analyses of multiple contingencies create analytical challenges, this complexity is needed to accurately specify the mental health effects of functional limitations. PMID- 17284566 TI - Weight and depressive symptoms in older adults: direction of influence? AB - OBJECTIVE: . The purpose of this study was to clarify the direction of the relationship between changes in depressive symptoms and changes in weight in older adults. Methods. The sample included a prospective cohort of individuals aged 53-63 (n = 9,130) enrolled in the Health and Retirement Study. We used separate cross-lagged models for men and women in order to study the impact of weight change on subsequent increases in depressive symptoms 2 years later and vice versa. RESULT: . Weight gain did not lead to increased depressive symptoms, and weight loss preceded increased depressive symptoms only in unadjusted models among men (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.04-1.53). Increased depressive symptoms were not predictive of subsequent weight loss, but they were predictive of subsequent weight gain in unadjusted models only (men: OR = 1.24, 95% CI = 1.00-1.54; women: OR = 1.12, 95% CI = 1.00-1.26). In adjusted models, baseline depressive symptoms predicted both weight loss and weight gain among both men and women. Increase in functional limitations and medical conditions were significant predictors of both weight loss and weight gain. Baseline functional limitations also predicted increased depressive symptoms. Discussion. Based on our findings, it is apparent that researchers need to examine the pathways between changes in weight and increases in depressive symptoms in the context of functional limitations and medical comorbidity. PMID- 17284567 TI - Urban neighborhoods and depressive symptoms among older adults. AB - OBJECTIVE: This study seeks to determine whether depressive symptoms among older persons systematically vary across urban neighborhoods such that experiencing more symptoms is associated with low socioeconomic status (SES), high concentrations of ethnic minorities, low residential stability and low proportion aged 65 years and older. METHODS: Survey data are from the Study of Assets and Health Dynamics Among the Oldest Old (AHEAD), a 1993 U.S. national probability sample of noninstitutionalized persons born in 1923 or earlier (i.e. people aged 70 or older). Neighborhood data are from the 1990 Census at the tract level. Hierarchical linear regression is used to estimate multilevel models. RESULT: The average number of depressive symptoms varies across Census tracts independent of individual-level characteristics. Symptoms are not significantly associated with neighborhood SES, ethnic composition, or age structure when individual-level characteristics are controlled statistically. However, net of individual-level characteristics, symptoms are positively associated with neighborhood residential stability, pointing to a complex meaning of residential stability for the older population. DISCUSSION: This study shows that apparent neighborhood-level socioeconomic effects on depressive symptoms among urban-dwelling older adults are largely if not entirely compositional in nature. Further, residential stability in the urban neighborhood may not be emotionally beneficial to its aged residents. PMID- 17284568 TI - Continuous participation in voluntary groups as a protective factor for the psychological well-being of adults who develop functional limitations: evidence from the national survey of families and households. AB - OBJECTIVES: Although previous studies have indicated that declining functional health is associated with individuals' poorer psychological well-being, few studies have examined factors that can protect adults from the loss of well-being following functional decline. Guided by continuity theory, this study investigated the extent to which continuous participation in voluntary groups (recreational, religious, and civic) buffers individuals against the harmful psychological effects of developing functional limitations. METHODS: Longitudinal data came from 4,646 respondents aged 35 to 92 in the National Survey of Families and Households (1987-1993) who reported having no functional limitations at Time 1. RESULTS: Multivariate models controlling for sociodemographic factors, as well as psychological well-being at Time 1, indicated that developing functional limitations over a 5-year period was associated with greater increases in depressive symptoms and lower levels of personal growth. Increases in depressive symptoms, however, were less severe among men who were continuously involved in recreational groups than among men who were not continuously involved in recreational groups. Additionally, the association between developing functional limitations and lower levels of personal growth did not hold for men or women who continuously participated in religious groups. DISCUSSION: Findings suggest that continuous participation in certain types of voluntary groups can moderate the problematic effects of developing functional limitations on psychological well being. PMID- 17284569 TI - Volunteering among older people in Korea. AB - OBJECTIVE: Faced with aging societies, there is an immense need to better understand the nature of volunteering outside advanced Western industrial countries. As a case of a rapidly aging society, we identify robust factors associated with elderly volunteering in Korea in terms of a resource framework. METHODS: Data were derived from the Social Statistics Survey conducted by the Korea National Statistical Office in 1999 (N = 7,135) and 2003 (N = 8,371). We first determined overall and age-related volunteer rates for Korea compared to the United States. Using logistic regression, we then examined the effects of human, cultural, and social capital variables on volunteering. RESULT: Approximately 6% of Koreans aged 65 years and older participate in volunteer programs. All human capital variables are positively related with volunteering. For cultural capital, those who identify their religion as Buddhism or Catholicism are more likely to volunteer than those who have no religion. But surprisingly, Protestantism does not consistently promote volunteering across both years. For social capital, older adults who live alone or with a spouse are more likely to volunteer than those living with both a spouse and children. DISCUSSION: In contrast to human capital, cultural and social capital on elderly volunteering appears to be contoured by social contexts. PMID- 17284570 TI - Experimental arthritis inhibits the insulin-like growth factor-I axis and induces muscle wasting through cyclooxygenase-2 activation. AB - Chronic arthritis induces cachexia associated with an inhibition of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) system and an activation of the E3 ubiquitin-ligating enzymes muscle atrophy F-box (MAFbx) and muscle Ring finger 1 (MuRF1) in the skeletal muscle. The aim of this work was to study the role of cyclooxygenase (COX)-2 in chronic arthritis-induced cachexia. Arthritis was induced in rats by Freund's adjuvant injection, and the effects of two COX inhibitors (indomethacin, a nonspecific inhibitor, and meloxicam, a selective COX 2 inhibitor on pituitary GH and on liver and serum IGF-I levels) were tested. Arthritis decreased body weight gain and GH and liver IGF-I gene expression. In the arthritic rats, both inhibitors, indomethacin and meloxicam, prevented the inhibitory effect of arthritis on body weight gain. Indomethacin and meloxicam administration to arthritic rats increased pituitary GH and liver IGF-I mRNA as well as serum levels of IGF-I. These data suggest that induction of COX-2 during chronic inflammation is involved in the inhibition of the GH-IGF-I axis and in the body weight loss. In the gastrocnemius muscle, arthritis increased the gene expression of tumor necrosis factor (TNF)-alpha, the E3 ubiquitin-ligating enzymes MAFbx and MuRF1, as well as of IGF-I and IGF-binding protein-5 (IGFBP-5). Inhibition of COX-2 by meloxicam administration increased gastrocnemius weight and decreased MAFbx, MuRF1, TNF-alpha, and IGFBP-5 gene expression. In summary, our data indicate that chronic arthritis-induced cachexia and muscle wasting are mediated by the COX-2 pathway resulting in a decreased GH-IGF-I secretion and increased expression of MAFbx and MuRF1 mRNA. PMID- 17284571 TI - Dysregulation of muscle lipid metabolism in rats selectively bred for low aerobic running capacity. AB - As substrate for evaluation of metabolic diseases, we developed novel rat models that contrast for endurance exercise capacity. Through two-way artificial selection, we created rodent phenotypes of intrinsically low-capacity runners (LCR) and high-capacity runners (HCR) that also differed markedly for cardiovascular and metabolic disease risk factors. Here, we determined skeletal muscle proteins with putative roles in lipid and carbohydrate metabolism to better understand the mechanisms underlying differences in whole body substrate handling between phenotypes. Animals (generation 16) differed for endurance running capacity by 295%. LCR animals had higher resting plasma glucose (6.58 +/- 0.45 vs. 6.09 +/- 0.45 mmol/l), insulin (0.48 +/- 0.03 vs. 0.32 +/- 0.02 ng/ml), nonesterified fatty acid (0.57 +/- 0.14 v 0.35 +/- 0.05 mM), and triglyceride (TG; 0.47 +/- 0.11 vs. 0.25 +/- 0.08 mmol/l) concentrations (all P < 0.05). Muscle TG (72.3 +/- 14.7 vs. 38.9 +/- 6.2 mmol/kg dry muscle wt; P < 0.05) and diacylglycerol (96 +/- 28 vs. 42 +/- 8 pmol/mg dry muscle wt; P < 0.05) contents were elevated in LCR vs. HCR rats. Accompanying the greater lipid accretion in LCR was increased fatty acid translocase/CD36 content (1,014 +/- 80 vs. 781 +/- 70 arbitrary units; P < 0.05) and reduced TG lipase activity (0.158 +/- 0.0125 vs. 0.274 +/- 0.018 mmol.min(-1).kg dry muscle wt(-1); P < 0.05). Muscle glycogen, GLUT4 protein, and basal phosphorylation states of AMP-activated protein kinase-alpha1, AMP-activated protein kinase-alpha2, and acetyl-CoA carboxylase were similar in LCR and HCR. In conclusion, rats with low intrinsic aerobic capacity demonstrate abnormalities in lipid-handling capacity. These disruptions may, in part, be responsible for the increased risk of metabolic disorders observed in this phenotype. PMID- 17284572 TI - The rapid activation of protein synthesis by growth hormone requires signaling through mTOR. AB - An important function of growth hormone (GH) is to promote cell and tissue growth, and a key component of these effects is the stimulation of protein synthesis. In this study, we demonstrate that, in H4IIE hepatoma cells, GH acutely activated protein synthesis through signaling via the mammalian target of rapamycin (mTOR) and specifically through the rapamycin-sensitive mTOR complex 1 (mTORC1). GH treatment enhanced the phosphorylation of two targets of mTOR signaling, 4E-BP1 and ribosomal protein S6. Phosphorylation of S6 and 4E-BP1 was maximal at 30-45 min and 10-20 min after GH stimulation, respectively. Both proteins modulate components of the translational machinery. The GH-induced phosphorylation of 4E-BP1 led to its dissociation from eIF4E and increased binding of eIF4E to eIF4G to form (active) eIF4F complexes. The ability of GH to stimulate the phosphorylation of S6 and 4E-BP1 was blocked by rapamycin. GH also led to the dephosphorylation of a third translational component linked to mTORC1, the elongation factor eEF2. Its regulation followed complex biphasic kinetics, both phases of which required mTOR signaling. GH rapidly activated both the MAP kinase (ERK) and PI 3-kinase pathways. Signaling through PI 3-kinase alone was, however, sufficient to activate the downstream mTORC1 pathway. Consistent with this, GH increased the phosphorylation of TSC2, an upstream regulator of mTORC1, at sites that are targets for Akt/PKB. Finally, the activation of overall protein synthesis by GH in H4IIE cells was essentially completely inhibited by wortmannin or rapamycin. These results demonstrate for the first time that mTORC1 plays a major role in the rapid activation of protein synthesis by GH. PMID- 17284573 TI - Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation. AB - White adipose tissue (WAT) mass is the main determinant of obesity and associated health risks. WAT expansion results from increases in white adipocyte cell number and size, which in turn reflect a series of shifts in the cellular metabolic state. To quantitatively profile the metabolic alterations occurring during de novo adipocyte formation, metabolic flux analysis (MFA) was used in conjunction with a novel modularity analysis algorithm on differentiating 3T3-L1 preadipocytes. Use of a type I collagen gel as an effective long-term culture substrate was also assessed. The calculated flux distributions predicted the sequential activation of several intracellular cross-compartmental pathways, including lipogenesis, the pentose phosphate pathway, and the malate cycle, in good agreement with earlier isotopic tracer experiments and gene profiling studies. Partition of the adipocyte metabolic network into highly interacting reaction subgroups suggested a functional reorganization of the major pathways consistent with the lipid-loading phenotype of the adipocyte. Flux and modularity analysis results together point to the flux distribution around pyruvate as a key indicator of adipocyte lipid accumulation. PMID- 17284574 TI - Endothelin-1 and pancreatic islet vasculature: studies in vivo and on isolated, vascularly perfused pancreatic islets. AB - Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor, which also stimulates insulin release. The aim of the present study was to evaluate whether exogenously administered ET-1 affected pancreatic islet blood flow in vivo in rats and the islet arteriolar reactivity in vitro in mice. Furthermore, we aimed to determine the ET-receptor subtype that was involved in such responses. When applying a microsphere technique for measurements of islet blood perfusion in vivo, we found that ET-1 (5 nmol/kg) consistently and markedly decreased total pancreatic and especially islet blood flow, despite having only minor effects on blood pressure. Neither endothelin A (ET(A)) receptor (BQ-123) nor endothelin-B (ET(B)) receptor (BQ-788) antagonists, alone or in combination, could prevent this reduction in blood flow. To avoid confounding interactions in vivo, we also examined the arteriolar vascular reactivity in isolated, perfused mouse islets. In the latter preparation, we demonstrated a dose-dependent constriction in response to ET-1. Administration of BQ-123 prevented this, whereas BQ-788 induced a right shift in the response. In conclusion, the pancreatic islet vasculature is highly sensitive to exogenous ET-1, which mediates its effect mainly through ET(A) receptors. PMID- 17284575 TI - Possible role of carbonic anhydrase in rat pancreatic islets: enzymatic, secretory, metabolic, ionic, and electrical aspects. AB - The presence of carbonic anhydrase (type V) was recently documented in rat and mouse pancreatic islet beta-cells by immunostaining and Western blotting. In the present study, the activity of carbonic anhydrase was measured in rat islet homogenates and shown to be about four times lower than in rat parotid cells. The pattern for the inhibitory action of acetazolamide on carbonic anhydrase activity also differed in islet and parotid cell homogenates, suggesting the presence of different isoenzymes. NaN3 inhibited carbonic anhydrase activity in islet homogenates and both D-[U-14C]glucose oxidation and glucose-stimulated insulin secretion. Acetazolamide (0.3-10.0 mM) also decreased glucose-induced insulin output but failed to affect adversely D-[U-14C]glucose oxidation, although it inhibited the conversion of D-[5-3H]glucose to [3H]OH and that of D-[U 14C]glucose to acidic metabolites. Hydrochlorothiazide (3.0-10.0 mM), which also caused a concentration-related inhibition of the secretory response, like acetazolamide (5.0-10.0 mM), decreased H(14)CO3- production from D-[U-14C]glucose (16.7 mM). Acetazolamide (5.0 mM) did not affect the activity of volume-sensitive anion channels in beta-cells but lowered intracellular pH and adversely affected both the bioelectrical response to d-glucose and its effect on the cytosolic concentration of Ca2+ in these cells. The lowering of cellular pH by acetazolamide, which could well be due to inhibition of carbonic anhydrase, might in turn account for inhibition of glycolysis. The perturbation of stimulus secretion coupling in the beta-cells exposed to acetazolamide may thus involve impaired circulation in the pyruvate-malate shuttle, altered mitochondrial Ca2+ accumulation, and perturbation of Cl- fluxes, resulting in both decreased bioelectrical activity and insulin release. PMID- 17284577 TI - Diet-induced ketosis increases capillary density without altered blood flow in rat brain. AB - It is recognized that ketone bodies, such as R-beta-hydroxybutyrate (beta-HB) and acetoacetate, are energy sources for the brain. As with glucose metabolism, monocarboxylate uptake by the brain is dependent on the function and regulation of its own transporter system. We concurrently investigated ketone body influx, blood flow, and regulation of monocarboxylate transporter (MCT-1) and glucose transporter (GLUT-1) in diet-induced ketotic (KG) rat brain. Regional blood-to brain beta-HB influx (micromol.g(-1).min(-1)) increased 40-fold with ketosis (4.8 +/- 1.8 plasmabeta-HB; mM) in all regions compared with the nonketotic groups (standard and no-fat diets); there were no changes in regional blood flow. Immunohistochemical staining revealed that GLUT-1 density (number/mm2) in the cortex was significantly elevated (40%) in the ketotic group compared with the standard and no-fat diet groups. MCT-1 was also markedly (3-fold) upregulated in the ketotic group compared with the standard diet group. In the standard diet group, 40% of the brain capillaries stained positive for MCT-1; this amount doubled with the ketotic diet. Western blot analysis of isolated microvessels from ketotic rat brain showed an eightfold increase in GLUT-1 and a threefold increase in MCT-1 compared with the standard diet group. These data suggest that diet-induced ketosis results in increased vascular density at the blood-brain barrier without changes in blood flow. The increase in extraction fraction and capillary density with increased plasma ketone bodies indicates a significant flux of substrates available for brain energy metabolism. PMID- 17284576 TI - Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. AB - Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30-40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (-0.8 +/- 0.5 vs. +0.7 +/- 0.3 mg.kg(-1).min(-1), P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine treated group showed significant reduction in mtDNA/nuclear DNA (-52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9). (31)P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r2 = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity. PMID- 17284578 TI - Role of phosphatidylinositol-3 kinase-gamma in the actions of glucagon-like peptide-2 on the murine small intestine. AB - Glucagon-like peptide-2 (GLP-2) enhances intestinal growth and function through a cAMP-linked G protein-coupled receptor (GPCR) expressed in the mucosal layer and enteric nervous system. Because the type 1B gamma-isoform of phosphatidylinositol 3-kinase (PI3-K) is activated by GPCRs, we determined whether this enzyme plays a role in the intestinal actions of GLP-2 by using PI3-Kgamma knockout (KO) mice. Wild-type (WT), heterozygous, and KO mice were treated with vehicle or 1 microg Gly2-GLP-2 (a long-acting analog) twice daily for 10 days and analyzed for changes in intestinal growth, motility, and cAMP production. Basal small intestinal wet weight was increased in KO mice in association with enhanced crypt villus height and crypt cell proliferation (P < 0.05-0.01). However, the GLP-2 induced changes in these parameters were not different between KO and WT animals. GLP-2 treatment also enhanced the number of mucous cells in the intestinal epithelium, but this effect was lost in the PI3-Kgamma KO mice. Both basal and GLP-2-induced suppression of intestinal transit were normal in KO mice. In contrast, the ability of GLP-2 to stimulate cAMP levels in isolated muscle strips was abrogated by loss of PI3-Kgamma, despite the expression of GLP-2 receptor mRNA transcripts in this tissue. Together, the results of this study demonstrate a role for PI3-Kgamma in basal but not GLP-2-induced small intestinal mucosal growth. However, PI3-Kgamma is important for the enhancement of mucous cell number by GLP-2 and in the ability of the GLP-2 receptor to couple to cAMP in the enteric nervous system. PMID- 17284579 TI - Beta-cell "rest" accompanies reduced first-pass hepatic insulin extraction in the insulin-resistant, fat-fed canine model. AB - During insulin resistance, glucose homeostasis is maintained by an increase in plasma insulin via increased secretion and/or decreased first-pass hepatic insulin extraction. However, the relative importance of insulin secretion vs. clearance to compensate for insulin resistance in obesity has yet to be determined. This study utilizes the fat-fed dog model to examine longitudinal changes in insulin secretion and first-pass hepatic insulin extraction during development of obesity and insulin resistance. Six dogs were fed an isocaloric diet with an approximately 8% increase in fat calories for 12 wk and evaluated at weeks 0, 6, and 12 for changes in 1) insulin sensitivity by euglycemic hyperinsulinemic clamp, 2) first-pass hepatic insulin extraction by direct assessment, and 3) glucose-stimulated insulin secretory response by hyperglycemic clamp. We found that 12 wk of a fat diet increased subcutaneous and visceral fat as assessed by MR imaging. Consistent with increased body fat, the dogs exhibited a approximately 30% decrease in insulin sensitivity and fasting hyperinsulinemia. Although insulin secretion was substantially increased at week 6, beta-cell sensitivity returned to prediet levels by week 12. However, peripheral hyperinsulinemia was maintained because of a significant decrease in first-pass hepatic insulin extraction, thus maintaining hyperinsulinemia, despite changes in insulin release. Our results indicate that when obesity and insulin resistance are induced by an isocaloric, increased-fat diet, an initial increase in insulin secretion by the beta-cells is followed by a decrease in first-pass hepatic insulin extraction. This may provide a secondary physiological mechanism to preserve pancreatic beta-cell function during insulin resistance. PMID- 17284580 TI - Estimation of beta-cell function from the data of the oral glucose tolerance test. AB - Although a hyperbolic relationship between insulin secretion and insulin sensitivity has been shown, the relationship has been often questioned. We examined the relationship using oral glucose tolerance test (OGTT)-derived indexes. A total of 374 Japanese subjects who had never been given a diagnosis of diabetes underwent a 75-g OGTT. In subjects with normal glucose tolerance (NGT), the ln [insulinogenic index (IGI)] was described by a linear function of ln (x) (x, insulin sensitivity index) in regression analysis when the reciprocal of the insulin resistance index in homeostasis model assessment, Matsuda's index, and oral glucose insulin sensitivity index were used as x. Because the 95% confidence interval of the slope of the regression line did not necessarily include -1, the relationships between IGI and x were not always hyperbolic, but power functions IGI x x(alpha) = a constant. We thought that IGI x x(alpha) was an appropriate beta-cell function estimate adjusted by insulin sensitivity and referred to it as beta-cell function index (BI). When Matsuda's index was employed as x, the BI values were decreased in subjects without NGT. Log BI had a better correlation with fasting plasma glucose (PG; FPG) and 2-h PG in non-NGT subjects than in NGT subjects. In subjects with any glucose tolerance, log BI was linearly correlated with 1-h PG and glucose spike (the difference between maximum PG and FPG). In conclusion, the relationship between insulin secretion and insulin sensitivity was not always hyperbolic. The BI is a useful tool in the estimation of beta-cell function with a mathematical basis. PMID- 17284581 TI - Nomenclature for two-component signaling elements of rice. PMID- 17284582 TI - ETHYLENE RESPONSE 1 histidine kinase activity of Arabidopsis promotes plant growth. PMID- 17284584 TI - Arabidopsis downy mildew resistance gene RPP27 encodes a receptor-like protein similar to CLAVATA2 and tomato Cf-9. PMID- 17284585 TI - Probing the interactions of proteins and nanoparticles. PMID- 17284586 TI - Characterization of Z-DNA as a nucleosome-boundary element in yeast Saccharomyces cerevisiae. AB - In this article, the effect of a d(CG) DNA dinucleotide repeat sequence on RNA polymerase II transcription is examined in yeast Saccharomyces cerevisiae. Our previous report shows that a d(CG)n dinucleotide repeat sequence located proximally upstream of the TATA box enhances transcription from a minimal CYC1 promoter in a manner that depends on its surrounding negative supercoiling. Here, we demonstrate that the d(CG)9 repeat sequence stimulates gene activity by forming a Z-DNA secondary structure. Furthermore, the extent of transcriptional enhancement by Z-DNA is promoter-specific and determined by its separation distance relative to the TATA box. The stimulatory effect exerted by promoter proximal Z-DNA is not affected by helical phasing relative to the TATA box, suggesting that Z-DNA effects transcription without interacting with the general transcription machinery by looping-out the intervening DNA. A nucleosome-scanning assay reveals that the d(CG)9 repeat sequence in the Z conformation blocks nucleosome formation, and it is found in the linker DNA with two flanking nucleosomes. This result suggests that Z-DNA formation proximally upstream of a promoter is sufficient to demarcate the boundaries of its neighboring nucleosomes, which produces transcriptionally favorable locations for the TATA box near the nucleosomal DNA-entry site and at dyad positions on the nucleosome. These findings suggest that Z-DNA formation in chromatin is a part of the "genomic code" for nucleosome positioning in vivo. PMID- 17284587 TI - Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcription. AB - Notch receptors control differentiation and contribute to pathologic states such as cancer by interacting directly with a transcription factor called CSL (for CBF 1/Suppressor of Hairless/Lag-1) to induce expression of target genes. A number of Notch-regulated targets, including genes of the hairy/enhancer-of-split family in organisms ranging from Drosophila to humans, are characterized by paired CSL binding sites in a characteristic head-to-head arrangement. Using a combination of structural and molecular approaches, we establish here that cooperative formation of dimeric Notch transcription complexes on promoters with paired sites is required to activate transcription. Our findings identify a mechanistic step that can account for the exquisite sensitivity of Notch target genes to variation in signal strength and developmental context, enable new strategies for sensitive and reliable identification of Notch target genes, and lay the groundwork for the development of Notch pathway inhibitors that are active on target genes containing paired sites. PMID- 17284588 TI - Loop formation in unfolded polypeptide chains on the picoseconds to microseconds time scale. AB - Intrachain loop formation allows unfolded polypeptide chains to search for favorable interactions during protein folding. We applied triplet-triplet energy transfer between a xanthone moiety and naphthylalanine to directly measure loop formation in various unfolded polypeptide chains with loop regions consisting of polyserine, poly(glycine-serine) or polyproline. By combination of femtosecond and nanosecond laserflash experiments loop formation could be studied over many orders of magnitude in time from picoseconds to microseconds. The results reveal processes on different time scales indicating motions on different hierarchical levels of the free energy surface. A minor (<15%) very fast reaction with a time constant of approximately 3 ps indicates equilibrium conformations with donor and acceptor in contact at the time of the laserflash. Complex kinetics of loop formation were observed on the 50- to 500-ps time scale, which indicate motions within a local well on the energy landscape. Conformations within this well can form loops by undergoing local motions without having to cross major barriers. Exponential kinetics observed on the 10- to 100-ns time scale are caused by diffusional processes involving large-scale motions that allow the polypeptide chain to explore the complete conformational space. These results indicate that the free energy landscape for unfolded polypeptide chains and native proteins have similar properties. The presence of local energy minima reduces the conformational space and accelerates the conformational search for energetically favorable local intrachain contacts. PMID- 17284589 TI - Exchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons. AB - The exchange factor directly activated by cAMP (Epac) is a newly discovered direct target for cAMP and a guanine-nucleotide exchange factor for the small GTPase Rap. Little is known about the neuronal functions of Epac. Here we show that activation of Epac by specific cAMP analogs or by the pituitary adenylate cyclase-activating polypeptide induces a potent activation of the Ca2+-sensitive big K+ channel, slight membrane hyperpolarization, and increased after hyperpolarization in cultured cerebellar granule cells. These effects involve activation of Rap and p38 MAPK, which mobilizes intracellular Ca2+ stores. These findings reveal a cAMP Epac-dependent and protein kinase A-independent signaling cascade that controls neuronal excitability. PMID- 17284590 TI - Cell stress modulates the function of splicing regulatory protein RBM4 in translation control. AB - RNA-binding motif protein 4 (RBM4) plays a regulatory role in alternative splicing of precursor mRNA. We show here that cell stress such as arsenite exposure induces phosphorylation of RBM4 at serine 309 and also drives its cytoplasmic accumulation and targeting to stress granule via the MKK(3/6)-p38 signaling pathway. Accordingly, RBM4 suppresses cap-dependent translation in a cis-element-dependent manner. However, RBM4 concomitantly activates internal ribosome entry site (IRES)-mediated translation likely by promoting the association of translation initiation factor eIF4A with IRES-containing mRNAs. Overexpression of RBM4 therefore mimics the effect of cell stress-induced signaling on translation initiation control. Whereas arsenite treatment promotes RBM4 loading onto IRES mRNAs and enhances RBM4-eIF4A interactions, a nonphosphorylatable mutant of RBM4 was unresponsive to arsenite stress and failed to activate IRES-mediated translation. Thus, our results uncover a previously unrecognized paradigm for the RNA-binding protein RBM4 in its phosphorylation modulated dual action as a suppressor of cap-dependent and enhancer of IRES mediated translation in response to stress signals. PMID- 17284591 TI - How to keep photoreceptors alive. PMID- 17284592 TI - Long-distance combinatorial linkage between methylation and acetylation on histone H3 N termini. AB - Individual posttranslational modifications (PTMs) on histones have well established roles in certain biological processes, notably transcriptional programming. Recent genomewide studies describe patterns of covalent modifications, such as H3 methylation and acetylation at promoters of specific target genes, or "bivalent domains," in stem cells, suggestive of a possible combinatorial interplay between PTMs on the same histone. However, detection of long-range PTM associations is often problematic in antibody-based or traditional mass spectrometric-based analyses. Here, histone H3 from a ciliate model was analyzed as an enriched source of transcriptionally active chromatin. Using a recently developed mass spectrometric approach, combinatorial modification states on single, long N-terminal H3 fragments (residues 1-50) were determined. The entire modification status of intact N termini was obtained and indicated correlations between K4 methylation and H3 acetylation. In addition, K4 and K27 methylation were identified concurrently on one H3 species. This methodology is applicable to other histones and larger polypeptides and will likely be a valuable tool in understanding the roles of combinatorial patterns of PTMs. PMID- 17284593 TI - Aquaglyceroporin PbAQP during intraerythrocytic development of the malaria parasite Plasmodium berghei. AB - The malaria parasite can use host plasma glycerol for lipid biosynthesis and membrane biogenesis during the asexual intraerythrocytic development. The molecular basis for glycerol uptake into the parasite is undefined. We hypothesize that the Plasmodium aquaglyceroporin provides the pathway for glycerol uptake into the malaria parasite. To test this hypothesis, we identified the orthologue of Plasmodium falciparum aquaglyceroporin (PfAQP) in the rodent malaria parasite, Plasmodium berghei (PbAQP), and examined the biological role of PbAQP by performing a targeted deletion of the PbAQP gene. PbAQP and PfAQP are 62% identical in sequence. In contrast to the canonical NPA (Asn-Pro-Ala) motifs in most aquaporins, the PbAQP has NLA (Asn-Leu-Ala) and NPS (Asn-Leu-Ser) in those positions. PbAQP expressed in Xenopus oocytes was permeable to water and glycerol, suggesting that PbAQP is an aquaglyceroporin. In P. berghei, PbAQP was localized to the parasite plasma membrane. The PbAQP-null parasites were viable; however, they were highly deficient in glycerol transport. In addition, they proliferated more slowly compared with the WT parasites, and mice infected with PbAQP-null parasites survived longer. Taken together, these findings suggest that PbAQP provides the pathway for the entry of glycerol into P. berghei and contributes to the growth of the parasite during the asexual intraerythrocytic stages of infection. In conclusion, we demonstrate here that PbAQP plays an important role in the blood-stage development of the rodent malaria parasite during infection in mice and could be added to the list of targets for the design of antimalarial drugs. PMID- 17284595 TI - Silencing of estrogen receptor alpha in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. AB - Estrogen receptor alpha (ERalpha) plays a pivotal role in the regulation of food intake and energy expenditure by estrogens. Although it is well documented that a disruption of ERalpha signaling in ERalpha knockout (ERKO) mice leads to an obese phenotype, the sites of estrogen action and mechanisms underlying this phenomenon are still largely unknown. In the present study, we exploited RNA interference mediated by adeno-associated viral vectors to achieve focused silencing of ERalpha in the ventromedial nucleus of the hypothalamus, a key center of energy homeostasis. After suppression of ERalpha expression in this nucleus, female mice and rats developed a phenotype characteristic for metabolic syndrome and marked by obesity, hyperphagia, impaired tolerance to glucose, and reduced energy expenditure. This phenotype persisted despite normal ERalpha levels elsewhere in the brain. Although an increase in food intake preceded weight gain, our data suggest that a leading factor of obesity in this model is likely a decline in energy expenditure with all three major constituents being affected, including voluntary activity, basal metabolic rate, and diet-induced thermogenesis. Together, these findings indicate that ERalpha in the ventromedial nucleus of the hypothalamus neurons plays an essential role in the control of energy balance and the maintenance of normal body weight. PMID- 17284594 TI - Differential requirement for MuSK and dystroglycan in generating patterns of neuromuscular innervation. AB - Vertebrates display diverse patterns of neuromuscular innervation, but little is known about how such diversity is generated. In mammals, neuromuscular junctions form predominantly at equatorial locations, giving rise to a focal innervation pattern along a central endplate band. In addition, vertebrate striated muscles exhibit two nonfocal neuromuscular patterns, myoseptal and distributed innervation. Although agrin-MuSK-rapsyn signaling is essential for the focal innervation pattern, it is unknown whether the same genetic program also controls synaptogenesis at nonfocal innervation sites. Here we show that one of three transcripts generated by the zebrafish unplugged locus, unplugged FL, encodes the zebrafish MuSK ortholog. We demonstrate that UnpFL/MuSK is critical for the assembly of focal synapses in zebrafish and that it cooperates with dystroglycan in the formation of nonfocal myoseptal and distributed synapses. Our results provide the first genetic evidence that neuromuscular synapse formation can occur in the absence of MuSK and that the combinatorial function of UnpFL/MuSK and dystroglycan generates diverse patterns of vertebrate neuromuscular innervation. PMID- 17284596 TI - Dietary sequestration of defensive steroids in nuchal glands of the Asian snake Rhabdophis tigrinus. AB - The Asian snake Rhabdophis tigrinus possesses specialized defensive glands on its neck that contain steroidal toxins known as bufadienolides. We hypothesized that R. tigrinus does not synthesize these defensive steroids but instead sequesters the toxins from toads it consumes as prey. To test this hypothesis, we conducted chemical analyses on the glandular fluid from snakes collected in toad-free and toad-present localities. We also performed feeding experiments in which hatchling R. tigrinus were reared on controlled diets that either included or lacked toads. We demonstrate that the cardiotonic steroids in the nuchal glands of R. tigrinus are obtained from dietary toads. We further show that mothers containing high levels of bufadienolides can provision their offspring with toxins. Hatchlings had bufadienolides in their nuchal glands only if they were fed toads or were born to a dam with high concentrations of these compounds. Because geographic patterns in the availability of toxic prey are reflected in the chemical composition of the glandular fluid, snakes in toad-free regions are left undefended by steroidal toxins. Our findings confirm that the sequestration of dietary toxins underlies geographic variation in antipredatory behavior in this species and provide a unique example of sequestered defensive compounds in a specialized vertebrate structure. PMID- 17284597 TI - Interleukin 7 reduces the levels of spontaneous apoptosis in CD4+ and CD8+ T cells from HIV-1-infected individuals. AB - Apoptosis has been suggested as one of the major mechanisms of CD4+ T cell depletion during the course of HIV type 1 (HIV-1) infection. Here, we show that interleukin 7 (IL-7), a nonredundant cytokine that plays essential roles in the generation and homeostasis of the T cell compartment of the immune system, exerts strong antiapoptotic effects ex vivo on both CD4+ and CD8+ T cells derived from HIV-1-infected subjects. The level of IL-7-mediated reduction of apoptosis was inversely correlated with the number of circulating CD4+ T cells, indicating a higher sensitivity to IL-7 effects in patients with more advanced disease. The antiapoptotic effect of IL-7 was uncoupled from the induction of cellular proliferation or endogenous HIV-1 replication. These results provide a further rationale for consideration of IL-7 as an agent of immune reconstitution in HIV-1 infection. PMID- 17284598 TI - An antibiotic produced by an insect-pathogenic bacterium suppresses host defenses through phenoloxidase inhibition. AB - Photorhabdus is a virulent pathogen that kills its insect host by overcoming immune responses. The bacterium also secretes a range of antibiotics to suppress the growth of other invading microorganisms. Here we show that Photorhabdus produces a small-molecule antibiotic (E)-1,3-dihydroxy-2-(isopropyl)-5-(2 phenylethenyl)benzene (ST) that also acts as an inhibitor of phenoloxidase (PO) in the insect host Manduca sexta. The Photorhabdus gene stlA encodes an enzyme that produces cinnamic acid, a key precursor for production of ST, and a mutation in stlA results in loss of ST production and PO inhibitory activity, which are both restored by genetic complementation of the mutant and also by supplying cinnamic acid. ST is produced both in vitro and in vivo in sufficient quantities to account for PO inhibition and is the only detectable solvent-extractable inhibitor. A Photorhabdus stlA- mutant is significantly less virulent, proliferates slower within the host, and provokes the formation of significantly more melanotic nodules than wild-type bacteria. Virulence of the stlA- mutant is also rescued by supplying cinnamic acid. The proximate cause of the virulence effect, however, is the inhibition of PO, because the effect of the stlA- mutation on virulence is abolished in insects in which PO has been knocked down by RNA interference (RNAi). Thus, ST has a dual function both as a PO inhibitor to counter host immune reactions and also as an antibiotic to exclude microbial competitors from the insect cadaver. PMID- 17284601 TI - Telomere dysfunction as a cause of genomic instability in Werner syndrome. AB - Werner syndrome (WS) is a rare human premature aging disease caused by mutations in the gene encoding the RecQ helicase WRN. In addition to the aging features, this disorder is marked by genomic instability, associated with an elevated incidence of cancer. Several lines of evidence suggest that telomere dysfunction is associated with the aging phenotype of the syndrome; however, the origin of the genomic instability observed in WS cells and the reason for the high incidence of cancer in WS have not been established. We previously proposed that WRN helicase activity was necessary to prevent dramatic telomere loss during DNA replication. Here we demonstrate that replication-associated telomere loss is responsible for the chromosome fusions found in WS fibroblasts. Moreover, using metaphase analysis we show that telomere elongation by telomerase can significantly reduce the appearance of new chromosomal aberrations in cells lacking WRN, similar to complementation of WS cells with WRN. Our results suggest that the genome instability in WS cells depends directly on telomere dysfunction, linking chromosome end maintenance to chromosomal aberrations in this disease. PMID- 17284600 TI - Identification and functional expression of the Arabidopsis thaliana vacuolar glucose transporter 1 and its role in seed germination and flowering. AB - Sugar compartmentation into vacuoles of higher plants is a very important physiological process, providing extra space for transient and long-term sugar storage and contributing to the osmoregulation of cell turgor and shape. Despite the long-standing knowledge of this subcellular sugar partitioning, the proteins responsible for these transport steps have remained unknown. We have identified a gene family in Arabidopsis consisting of three members homologous to known sugar transporters. One member of this family, Arabidopsis thaliana vacuolar glucose transporter 1 (AtVGT1), was localized to the vacuolar membrane. Moreover, we provide evidence for transport activity of a tonoplast sugar transporter based on its functional expression in bakers' yeast and uptake studies in isolated yeast vacuoles. Analyses of Atvgt1 mutant lines indicate an important function of this vacuolar glucose transporter during developmental processes like seed germination and flowering. PMID- 17284602 TI - Phase-variable expression of a family of glycoproteins imparts a dynamic surface to a symbiont in its human intestinal ecosystem. AB - The recent report of the synthesis of glycoproteins by the abundant intestinal symbionts Bacteroides showed that these organisms use a novel bacterial enzyme to decorate their surfaces with a sugar residue derived from their environment. As a first step in understanding the importance of these glycoproteins to the bacteria and to the bacterial-host symbiosis, we identified and characterized the abundant glycoproteins of Bacteroides distasonis (proposed reclassification as Parabacteroides distasonis) [Sakamoto M, Benno Y (2006) Int J Syst Evol Microbiol 56:1599-1605]. Using lectin-affinity purification followed by tandem mass spectrometry, we identified a family of at least nine glycoproteins, similar only to the S-layer glycoproteins of Tannerella forsythia. Analysis of one of these purified glycoproteins demonstrated that the glycan is primarily a polymer of xylose, a monosaccharide rarely found in bacterial glycans. Even more unexpected was the finding that seven of nine of the glycoprotein promoters undergo DNA inversion, a process that we show is active in their endogenous human environment. Using cross-species functional assays, we show that a single serine family site-specific recombinase globally mediates the inversions of these glycoprotein promoters. This regulatory mechanism is similar to that of the Bacteroides fragilis capsular polysaccharides and establishes DNA inversion as a general and ancient means of regulation of glycan-containing surface molecules of these important human intestinal symbionts. PMID- 17284603 TI - Common mechanisms of target cell recognition and immunity for class II bacteriocins. AB - The mechanisms of target cell recognition and producer cell self-protection (immunity) are both important yet poorly understood issues in the biology of peptide bacteriocins. In this report, we provide genetic and biochemical evidence that lactococcin A, a permeabilizing peptide-bacteriocin from Lactococcus lactis, uses components of the mannose phosphotransferase system (man-PTS) of susceptible cells as target/receptor. We present experimental evidence that the immunity protein LciA forms a strong complex with the receptor proteins and the bacteriocin, thereby preventing cells from being killed. Importantly, the complex between LciA and the man-PTS components (IIAB, IIC, and IID) appears to involve an on-off type mechanism that allows complex formation only in the presence of bacteriocin; otherwise no complexes were observed between LciA and the receptor proteins. Deletion of the man-PTS operon combined with biochemical studies revealed that the presence of the membrane-located components IIC and IID was sufficient for sensitivity to lactococcin A as well as complex formation with LciA. The cytoplasmic component of the man-PTS, IIAB, was not required for the biological sensitivity or for complex formation. Furthermore, heterologous expression of the lactococcal man-PTS operon rendered the insensitive Lactobacillus sakei susceptible to lactococcin A. We also provide evidence that, not only lactococcin A, but other class II peptide-bacteriocins including lactococcin B and some Listeria-active pediocin-like bacteriocins also target the man-PTS components IIC and IID on susceptible cells and that their immunity proteins involve a mechanism in producer cell self-protection similar to that observed for LciA. PMID- 17284604 TI - Reactive oxygen species detoxification by catalase is a major determinant of fecundity in the mosquito Anopheles gambiae. AB - The mosquito Anopheles gambiae is a primary vector of Plasmodium parasites in Africa. The effect of aging on reproductive output in A. gambiae females from three strains that differ in their ability to melanize Plasmodium and in their systemic levels of hydrogen peroxide (H2O2), a reactive oxygen species (ROS), was analyzed. The number of eggs oviposited after the first blood meal decreases with age in all strains; however, this decline was much more pronounced in the G3 (unselected) and R (refractory to Plasmodium infection) strains than in the S (highly susceptible to Plasmodium) strain. Reduction of ROS levels in G3 and R females by administration of antioxidants reversed this age-related decline in fecundity. The S and G3 strains were fixed for two functionally different catalase alleles that differ at the second amino acid position (Ser2Trp). Biochemical analysis of recombinant proteins revealed that the Trp isoform has lower specific activity and higher Km than the Ser isoform, indicating that the former is a less efficient enzyme. The Trp-for-Ser substitution appears to destabilize the functional tetrameric form of the enzyme. Both alleles are present in the R strain, and Ser/Ser females had significantly higher fecundity than Trp/Trp females. Finally, a systemic reduction in catalase activity by dsRNA mediated knockdown significantly reduced the reproductive output of mosquito females, indicating that catalase plays a central role in protecting the oocyte and early embryo from ROS damage. PMID- 17284605 TI - Direct action of gonadotropin in brain integrates behavioral and reproductive functions. AB - Essential roles for gonadotropins in gonadal development and reproduction are well established. Over the past decade, however, the expression of luteinizing hormone receptor (LHR) has also been reported in the brain of various mammals and birds. Although suggestive, it has not yet been determined whether this expression pattern supports a novel function for gonadotropins. Here, we demonstrate a CNS-mediated role of gonadotropins in a reproductive behavior: the courtship songs of the South African clawed frog, Xenopus laevis. Male advertisement calling in this species depends on a nongonadal action of gonadotropin. To determine whether this effect is due to action on the CNS, we administered gonadotropin intracerebroventricularly (ICV) or systemically to intact or castrated males with or without concomitant androgen replacement. In intact and androgen-replaced gonadectomized males, gonadotropin significantly increased calling within 1 h after ICV injection. The effective dosage via ICV injections was less than one hundredth of the effective systemic dose. In situ hybridization with a cloned fragment of Xenopus LHR revealed strong expression in ventral forebrain areas important for vocal control. Further, gonadotropin treatment of brain in vitro up-regulates immunoreactivity for the LHR downstream target, egr-1, specifically in these vocal forebrain areas. Up-regulation occurs even when synaptic transmission is suppressed by incubation in Ca2+ free/high magnesium saline. These results demonstrate a neural role for gonadotropin in the control of calling behavior, potentially mediated via LHRs in forebrain vocal nuclei. Gonadotropin may play a novel integrative role in modulating both reproductive physiology and behavior. PMID- 17284599 TI - Adaptive genic evolution in the Drosophila genomes. AB - Determining the extent of adaptive evolution at the genomic level is central to our understanding of molecular evolution. A suitable observation for this purpose would consist of polymorphic data on a large and unbiased collection of genes from two closely related species, each having a large and stable population. In this study, we sequenced 419 genes from 24 lines of Drosophila melanogaster and its close relatives. Together with data from Drosophila simulans, these data reveal the following. (i) Approximately 10% of the loci in regions of normal recombination are much less polymorphic at silent sites than expected, hinting at the action of selective sweeps. (ii) The level of polymorphism is negatively correlated with the rate of nonsynonymous divergence across loci. Thus, even under strict neutrality, the ratio of amino acid to silent nucleotide changes (A:S) between Drosophila species is expected to be 25-40% higher than the A:S ratio for polymorphism when data are pooled across the genome. (iii) The observed A/S ratio between species among the 419 loci is 28.9% higher than the (adjusted) neutral expectation. We estimate that nearly 30% of the amino acid substitutions between D. melanogaster and its close relatives were adaptive. (iv) This signature of adaptive evolution is observable only in regions of normal recombination. Hence, the low level of polymorphism observed in regions of reduced recombination may not be driven primarily by positive selection. Finally, we discuss the theories and data pertaining to the interpretation of adaptive evolution in genomic studies. PMID- 17284607 TI - Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. AB - Photoreceptor apoptosis is a major cause of visual loss in retinal detachment (RD) and several other visual disorders, but the underlying mechanisms remain elusive. Recently, increased expression of monocyte chemoattractant protein 1 (MCP-1) was reported in vitreous humor samples of patients with RD and diabetic retinopathy as well as in the brain tissues of patients with neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Here we report that MCP-1 plays a critical role in mediating photoreceptor apoptosis in an experimental model of RD. RD led to increased MCP-1 expression in the Muller glia and increased CD11b+ macrophage/microglia in the detached retina. An MCP-1 blocking antibody greatly reduced macrophage/microglia infiltration and RD induced photoreceptor apoptosis. Confirming these results, MCP-1 gene-deficient mice showed significantly reduced macrophage/microglia infiltration after RD and very little photoreceptor apoptosis. In primary retinal mixed cultures, MCP-1 was cytotoxic for recoverin+ photoreceptors, and this toxicity was eliminated through immunodepleting macrophage/microglia from the culture. In vivo, deletion of the gene encoding CD11b/CD18 nearly eliminated macrophage/microglia infiltration to the retina after RD and the loss of photoreceptors. Thus, MCP-1 expression and subsequent macrophage/microglia infiltration and activation are critical for RD induced photoreceptor apoptosis. This pathway may be an important therapeutic target for preventing photoreceptor apoptosis in RD and other CNS diseases that share a common etiology. PMID- 17284608 TI - Morphological mechanism of the development of pulmonary emphysema in klotho mice. AB - The concept of fractal geometry is useful for the analysis of irregular and complex structures often seen in nature. Here we apply this concept to investigate the structural mechanism of the development of pulmonary emphysema in the klotho mouse, which, after milk feeding, exhibits characteristics resembling aging and develops emphysema. We calculated the relationships between perimeter and size characterizing shape and between cumulative frequency and size of the terminal air spaces identified from histologic slides and found that both relations followed a power law with fractal properties. However, the fractal dimensions related to the shape and size (Dsn) in the klotho mice were significantly lower than in controls. Additionally, in the klotho mice, Dsn decreased with age without significant change in mean linear intercept. These abnormal morphological changes were restored when the klotho mice were fed with a vitamin D-deficient diet. Previously undescribed morphological model simulations showed that a random destruction, in which the destruction process occurs homogeneously in the lungs, was more consistent with the data than a correlated destruction that is usually seen in smoking-related human emphysema. These results suggest that the pathological changes in the lungs of the klotho mice are derived not from localized causes, but from systemic causes that are related to abnormal activation of vitamin D. The morphogenesis of emphysema in the klotho mice and morphological analyses using fractal geometry may contribute to the understanding of the progressive nature and cause of parenchymal destruction in human emphysema. PMID- 17284606 TI - Acute postnatal ablation of Hif-2alpha results in anemia. AB - Adaptive transcriptional responses to oxygen deprivation (hypoxia) are mediated by the hypoxia-inducible factors (HIFs), heterodimeric transcription factors composed of two basic helix-loop-helix-PAS family proteins. The transcriptional activity of HIF is determined by the hypoxic stabilization of the HIF-alpha proteins. HIF-1alpha and HIF-2alpha exhibit high sequence homology but have different mRNA expression patterns; HIF-1alpha is expressed ubiquitously whereas HIF-2alpha expression is more restricted to certain tissues, e.g., the endothelium, lung, brain, and neural crest derivatives. Germ-line deletion of either HIF subunit is embryonic lethal with unique features suggesting important roles for both HIF-alpha isoforms. Global deletion of Hif-2alpha results in distinct phenotypes depending on the mouse strain used for the mutation, clearly demonstrating an important role for HIF-2alpha in mouse development. The function of HIF-2alpha in adult life, however, remains incompletely understood. In this study, we describe the generation of a conditional murine Hif-2alpha allele and the effect of its acute postnatal ablation. Under very stringent conditions, we ablate Hif-2alpha after birth and compare the effect of acute global deletion of Hif-2alpha and Hif-1alpha. Our results demonstrate that HIF-2alpha plays a critical role in adult erythropoiesis, with acute deletion leading to anemia. Furthermore, although HIF-1alpha was first purified and cloned based on its affinity for the human erythropoietin (EPO) 3' enhancer hypoxia response element (HRE) and regulates Epo expression during mouse embryogenesis, HIF-2alpha is the critical alpha isoform regulating Epo under physiologic and stress conditions in adults. PMID- 17284609 TI - A catalytic beacon sensor for uranium with parts-per-trillion sensitivity and millionfold selectivity. AB - Here, we report a catalytic beacon sensor for uranyl (UO2(2+)) based on an in vitro-selected UO2(2+)-specific DNAzyme. The sensor consists of a DNA enzyme strand with a 3' quencher and a DNA substrate with a ribonucleotide adenosine (rA) in the middle and a fluorophore and a quencher at the 5' and 3' ends, respectively. The presence of UO2(2+) causes catalytic cleavage of the DNA substrate strand at the rA position and release of the fluorophore and thus dramatic increase of fluorescence intensity. The sensor has a detection limit of 11 parts per trillion (45 pM), a dynamic range up to 400 nM, and selectivity of >1-million-fold over other metal ions. The most interfering metal ion, Th(IV), interacts with the fluorescein fluorophore, causing slightly enhanced fluorescence intensity, with an apparent dissociation constant of approximately 230 microM. This sensor rivals the most sensitive analytical instruments for uranium detection, and its application in detecting uranium in contaminated soil samples is also demonstrated. This work shows that simple, cost-effective, and portable metal sensors can be obtained with similar sensitivity and selectivity as much more expensive and sophisticated analytical instruments. Such a sensor will play an important role in environmental remediation of radionuclides such as uranium. PMID- 17284610 TI - Wnt signaling interacts with Shh to regulate taste papilla development. AB - Wnt and Shh signaling pathways are critical for the development and maturation of many epithelial tissues. Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expression in fungiform papillae and formation of normal mature fungiform papillae depend on signaling through Wnt and beta-catenin. We observed that during fungiform papilla formation in mice, Shh and components of the Wnt/beta catenin signaling pathway are expressed together in the developing placode. The elimination of Wnt/beta-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression. In addition, the size and number of fungiform papillae were greatly reduced in Lef1 knockout mice. By examining embryonic mouse tongues in culture we determined that activation of Wnt/beta catenin signaling up-regulates Shh expression. We observed that blocking Shh signaling in cultured tongue explants enhanced papillae formation and was accompanied by an up-regulation of Wnt/beta-catenin signaling, indicating that Shh inhibits the Wnt/beta-catenin pathway. Exogenously added Shh suppressed expression of endogenous Shh and inhibited Wnt/beta-catenin signaling (assessed in TOPGAL mice), further implicating Shh as an inhibitor of the Wnt/beta-catenin pathway. Our observations indicate that Wnt/beta-catenin signaling and interactions between the Wnt and Shh pathways play essential roles in the development of fungiform papillae. PMID- 17284611 TI - Eukaryotic RNase P RNA mediates cleavage in the absence of protein. AB - The universally conserved ribonucleoprotein RNase P is involved in the processing of tRNA precursor transcripts. RNase P consists of one RNA and, depending on its origin, a variable number of protein subunits. Catalytic activity of the RNA moiety so far has been demonstrated only for bacterial and some archaeal RNase P RNAs but not for their eukaryotic counterparts. Here, we show that RNase P RNAs from humans and the lower eukaryote Giardia lamblia mediate cleavage of four tRNA precursors and a model RNA hairpin loop substrate in the absence of protein. Compared with bacterial RNase P RNA, the rate of cleavage (k(obs)) was five to six orders of magnitude lower, whereas the affinity for the substrate (appK(d)) was reduced approximately 20- to 50-fold. We conclude that the RNA-based catalytic activity of RNase P has been preserved during evolution. This finding opens previously undescribed ways to study the role of the different proteins subunits of eukaryotic RNase P. PMID- 17284612 TI - Plasticity of genetic interactions in metabolic networks of yeast. AB - Why are most genes dispensable? The impact of gene deletions may depend on the environment (plasticity), the presence of compensatory mechanisms (mutational robustness), or both. Here, we analyze the interaction between these two forces by exploring the condition-dependence of synthetic genetic interactions that define redundant functions and alternative pathways. We performed systems-level flux balance analysis of the yeast (Saccharomyces cerevisiae) metabolic network to identify genetic interactions and then tested the model's predictions with in vivo gene-deletion studies. We found that the majority of synthetic genetic interactions are restricted to certain environmental conditions, partly because of the lack of compensation under some (but not all) nutrient conditions. Moreover, the phylogenetic cooccurrence of synthetically interacting pairs is not significantly different from random expectation. These findings suggest that these gene pairs have at least partially independent functions, and, hence, compensation is only a byproduct of their evolutionary history. Experimental analyses that used multiple gene deletion strains not only confirmed predictions of the model but also showed that investigation of false predictions may both improve functional annotation within the model and also lead to the discovery of higher-order genetic interactions. Our work supports the view that functional redundancy may be more apparent than real, and it offers a unified framework for the evolution of environmental adaptation and mutational robustness. PMID- 17284613 TI - Regulation of yeast oscillatory dynamics. AB - When yeast cells are grown continuously at high cell density, a respiratory oscillation percolates throughout the population. Many essential cellular functions have been shown to be separated temporally during each cycle; however, the regulatory mechanisms involved in oscillatory dynamics remain to be elucidated. Through GC-MS analysis we found that the majority of metabolites show oscillatory dynamics, with 70% of the identified metabolite concentrations peaking in conjunction with NAD(P)H. Through statistical analyses of microarray data, we identified that biosynthetic events have a defined order, and this program is initiated when respiration rates are increasing. We then combined metabolic, transcriptional data and statistical analyses of transcription factor activity, identified the top oscillatory parameters, and filtered a large-scale yeast interaction network according to these parameters. The analyses and controlled experimental perturbation provided evidence that a transcriptional complex formed part of the timing circuit for biosynthetic, reductive, and cell cycle programs in the cell. This circuitry does not act in isolation because both have strong translational, proteomic, and metabolic regulatory mechanisms. Our data lead us to conclude that the regulation of the respiratory oscillation revolves around coupled subgraphs containing large numbers of proteins and metabolites, with a potential to oscillate, and no definable hierarchy, i.e., heterarchical control. PMID- 17284615 TI - Sustainability science: a room of its own. PMID- 17284616 TI - Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines. AB - BACKGROUND: Treatment-related neurotoxicity has been recognized as a significant problem in patients with primary central nervous system lymphoma (PCNSL) as effective treatment has increased survival rates. There is, however, a paucity of research on cognitive functions in this population. DESIGN: In a review of the literature, a total of 17 articles that described cognitive outcome in adult PCNSL patients were identified. RESULTS: The studies that assessed cognitive functions after whole-brain radiotherapy combined with chemotherapy reported cognitive impairment in most patients. Patients treated with chemotherapy alone had either stable or improved cognitive performance in most studies. Methodological problems, however, limited the ability to ascertain the specific contribution of disease and various treatment interventions to cognitive outcome. On the basis of the literature review, a battery of cognitive and quality-of-life (QoL) measures to be used in prospective clinical trials was proposed. The battery is composed of five standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (attention, executive functions, memory, psychomotor speed), and QoL questionnaires, and meets criteria for use in collaborative trials. CONCLUSION: The incorporation of formal and systematic cognitive evaluations in PCNSL studies will improve our understanding of treatment-related neurotoxicity in this population. PMID- 17284614 TI - Lnk negatively regulates self-renewal of hematopoietic stem cells by modifying thrombopoietin-mediated signal transduction. AB - One of the central tasks of stem cell biology is to understand the molecular mechanisms that control self-renewal in stem cells. Several cytokines are implicated as crucial regulators of hematopoietic stem cells (HSCs), but little is known about intracellular signaling for HSC self-renewal. To address this issue, we attempted to clarify how self-renewal potential is enhanced in HSCs without the adaptor molecule Lnk, as in Lnk-deficient mice HSCs are expanded in number >10-fold because of their increased self-renewal potential. We show that Lnk negatively regulates self-renewal of HSCs by modifying thrombopoietin (TPO) mediated signal transduction. Single-cell cultures showed that Lnk-deficient HSCs are hypersensitive to TPO. Competitive repopulation revealed that long-term repopulating activity increases in Lnk-deficient HSCs, but not in WT HSCs, when these cells are cultured in the presence of TPO with or without stem cell factor. Single-cell transplantation of each of the paired daughter cells indicated that a combination of stem cell factor and TPO efficiently induces symmetrical self renewal division in Lnk-deficient HSCs but not in WT HSCs. Newly developed single cell immunostaining demonstrated significant enhancement of both p38 MAPK inactivation and STAT5 and Akt activation in Lnk-deficient HSCs after stimulation with TPO. Our results suggest that a balance in positive and negative signals downstream from the TPO signal plays a role in the regulation of the probability of self-renewal in HSCs. In general, likewise, the fate of stem cells may be determined by combinational changes in multiple signal transduction pathways. PMID- 17284617 TI - Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. AB - CONTEXT: At present, women with type 1 diabetes (DM1) are being treated with supraphysiological doses of exogenous insulin with the aim of providing a strict metabolic control, thereby avoiding the long-term complications of this disease. We hypothesized that PCOS would be especially prevalent in DM1, as might happen in any condition in which the ovary and the adrenals are exposed to excessive insulin concentrations. As will be seen in the present review, androgen excess and PCOS are very frequent complaints in women with DM1, yet nowadays hyperandrogenism is seldom diagnosed in these patients. EVIDENCE ACQUISITION: We conducted a systematic review of all the published studies addressing hyperandrogenic symptoms in women with DM1, identified through the Entrez-PubMed search engine, followed by a comprehensive review of the pathophysiology and clinical and laboratory features of PCOS in women with DM1. EVIDENCE SYNTHESIS: The prevalence of PCOS in adult women with DM1 is 12-18, 40, and 31% using National Institute for Child Health and Human Development, Rotterdam, and Androgen Excess Society criteria, respectively. Mild hirsutism and biochemical hyperandrogenism are present in 30 and 20% of the patients, respectively. In addition, menstrual abnormalities are observed in 20% of adult women with DM1, and a prevalence of 50% of polycystic ovarian morphology is reported. CONCLUSIONS: Physicians treating women with DM1 should be aware of the risk of hyperandrogenism in them and should include evaluation of hirsutism, menstrual abnormalities, and biochemical hyperandrogenism in their routine examinations. Future studies are needed to determine the best preventive and therapeutic options for the hyperandrogenism of these patients. PMID- 17284618 TI - Cranial irradiation and growth hormone neurosecretory dysfunction: a critical appraisal. AB - CONTEXT: It has been suggested that radiation-induced GH neurosecretory dysfunction exists in children; however, the pathophysiology is poorly understood, and it is unknown if such a phenomenon exists in adult life. STUDY SUBJECTS: Twenty-four-hour spontaneous GH secretion was studied by 20-min sampling both in the fed state (n = 16; six women) and the last 24 h of 33-h fast (n = 10; three women) in adult cancer survivors of normal GH status defined by two GH provocative tests, 13.1 +/- 1.6 (range, 3-28) yr after cranial irradiation (18-40 Gy) for nonpituitary brain tumors (n = 12) or leukemia (n = 4) in comparison with 30 (nine women) age- and body mass index-matched normal controls (fasting, 11 men and three women). RESULTS: Using previously published diagnostic thresholds, all patients had stimulated peak GH responses in the normal range to both the insulin tolerance test and the combined GHRH plus arginine stimulation test, as well as normal individual mean profile GH levels during the fed and fasting states. However, gender-specific comparisons revealed marked reduction (by 40%) in the overall peak GH responses to both provocative tests but similar GH secretory profiles; no differences were seen in the pulsatile attributes of GH secretion (cluster analysis) or the profile absolute and mean GH levels in the fed state or when the hypothalamic-pituitary axis was stimulated by fasting. CONCLUSIONS: Radiation-induced GH neurosecretory dysfunction either does not exist or is a very rare phenomenon in irradiated adult cancer survivors. The normality of physiological GH secretion in the context of reduced maximum somatotroph reserve suggests compensatory overdrive of the partially damaged somatotroph axis and constitutes a relative argument against somatotroph dysfunction being explained purely by hypothalamic damage with secondary atrophy due to GHRH deficiency. It is therefore possible that radiation in doses less than 40 Gy causes dual damage to both the pituitary and the hypothalamus. PMID- 17284619 TI - Absence of stabilizing mutations of beta-catenin encoded by CTNNB1 exon 3 in a large series of sporadic parathyroid adenomas. AB - CONTEXT: The molecular mechanisms underlying the pathogenesis of sporadic parathyroid adenomas are incompletely understood. Dysfunction of the Wnt signaling pathway is an established pathogenetic contributor to human tumorigenesis and, recently, the role of stabilizing mutations in beta-catenin, a cause of abnormal Wnt signaling, has been examined in parathyroid tumors with conflicting results. OBJECTIVE: The objective of the present study was to determine the frequency of stabilizing mutations in exon 3 of CTNNB1, encoding beta-catenin, in a large series of parathyroid adenomas. PATIENTS AND DESIGN: Ninety-seven sporadic parathyroid adenomas were examined for mutations in exon 3 of CTNNB1 by direct DNA sequencing. RESULTS: No mutations were identified in any of the adenomas. CONCLUSIONS: The absence of stabilizing mutations of beta catenin, including the previously reported S37A, encoded in CTNNB1 exon 3 among 97 tumors suggests that such mutations contribute rarely if at all to the development of sporadic parathyroid adenomas. A primary role for abnormal Wnt signaling in parathyroid tumor formation remains to be established. PMID- 17284620 TI - Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. AB - CONTEXT: Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. OBJECTIVE: Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. DESIGN AND SETTING: We conducted a cross-sectional study at a general clinical research center. STUDY PARTICIPANTS: A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. MAIN OUTCOME MEASURES: Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. RESULTS: Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. CONCLUSIONS: Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women. PMID- 17284621 TI - Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment. AB - CONTEXT: The serotonin and norepinephrine transporter inhibitor sibutramine is a widely used antiobesity drug. In acute studies, the peripheral sympathomimetic effect of sibutramine was counteracted by a central sympatholytic action. OBJECTIVE: The objective was to test the hypothesis that blood pressure responses to long-term sibutramine therapy may be related to sympathetic nerve traffic before treatment in a prospective open-label study in an academic clinical research center. PATIENTS: This study comprised 20 obese subjects (body mass index, 30-40 kg/m2; age, 30-57 yr) receiving 5 d of placebo treatment followed by open-label 15 mg/d sibutramine and hypocaloric diet over 12 wk. MAIN OUTCOME MEASURES: Body weight, blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) (microneurography), plasma catecholamines, and adipose tissue gene expression were measured. RESULTS: Open-label sibutramine treatment decreased body weight 4.1 kg (P<0.01) and MSNA 17 bursts per minute (P=0.001), and increased diastolic blood pressure 3 mm Hg (P<0.05) and heart rate 8 bpm (P<0.01). The change in blood pressure with sibutramine treatment was inversely correlated with initial MSNA (r2=0.34; P<0.01). Chronic sibutramine treatment increased adrenoreceptor gene expression and plasma catecholamines. CONCLUSIONS: The blood pressure response to sibutramine treatment is related to initial MSNA so that subjects with higher MSNA exhibit a smaller increase or even a decrease in blood pressure. The phenomenon might be explained by a sustained reduction in central sympathetic activity with sibutramine treatment. PMID- 17284622 TI - B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study. AB - CONTEXT: Graves' disease (GD) is a common TSH receptor autoantibody (TRAb) mediated disorder. Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B-lymphocyte depletion with the monoclonal antibody rituximab (RTX) might be of benefit in GD. OBJECTIVE/DESIGN: The objective of this prospective, controlled, nonrandomized study was to investigate the effect of RTX in GD. SETTING/PATIENTS: We studied 20 outpatients referred to a university clinic with newly diagnosed (four with relapse) untreated GD. Ten received RTX (+RTX), whereas 10 did not (-RTX). INTERVENTION: The patients received methimazole (MMI) for a median of 102 d (+RTX) and 110 d (-RTX) before the study. Patients in the +RTX group received 375 mg RTX/m(2) iv on d 1, 8, 15, and 22, and all patients were withdrawn from methimazole (MMI) at d 22. MAIN OUTCOME MEASURES: We measured time to relapse of hyperthyroidism and changes in autoantibody levels. RESULTS: Four patients in the +RTX group remained in remission with a median follow-up of 705 d (range, 435-904 d), whereas all the patients in the -RTX group had relapsed by d 393 (P < 0.05). All of the patients in remission had initial TRAb levels below 5 IU/liter (normal, <0.7 IU/liter). However, none of the five patients in the -RTX group with correspondingly low TRAb levels were in remission (P < 0.01). RTX treatment did not affect autoantibody levels to a greater extent than did MMI monotherapy. Two patients received glucocorticoids for joint pain after RTX therapy. CONCLUSIONS: RTX treatment may induce sustained remission in patients with GD with low TRAb levels. However, RTX did not affect autoantibody levels and seems ineffective in patients with high TRAb levels. At present, high cost, low efficacy, and potential side effects do not support use in uncomplicated GD. PMID- 17284623 TI - Altered skeletal muscle fiber composition and size precede whole-body insulin resistance in young men with low birth weight. AB - CONTEXT: Low birth weight (LBW), a surrogate marker of an adverse fetal milieu, is linked to muscle insulin resistance, impaired insulin-stimulated glycolysis, and future risk of type 2 diabetes. Skeletal muscle mass, fiber composition, and capillary density are important determinants of muscle function and metabolism, and alterations have been implicated in the pathogenesis of insulin resistance. OBJECTIVE: The aim of this study was to investigate whether an adverse fetal environment (LBW) induces permanent changes in skeletal muscle morphology, which may contribute to the dysmetabolic phenotype associated with LBW. DESIGN AND SUBJECTS: Vastus lateralis muscle was obtained by percutaneous biopsy from 20 healthy 19-yr-old men with birth weights at 10th percentile or lower for gestational age (LBW) and 20 normal birth weight controls, matched for body fat, physical fitness, and whole-body glucose disposal. Myofibrillar ATPase staining was used to classify muscle fibers as type I, IIa, and IIx (formerly type IIb), and double immunostaining was performed to stain capillaries (LBW, n=8; normal birth weight, n=12). RESULTS: LBW was associated with increased proportion of type IIx fibers (+66%; P=0.03), at the expense of decreased type IIa fibers ( 22%; P=0.003). No significant change was observed in proportion of type I fibers (+16%; P=0.11). In addition, mean area of type IIa fibers was increased (+29%; P=0.01) and tended to be increased for type I fibers as well (+17%; P=0.08). Capillary density was not significantly different between groups. CONCLUSION: Alterations in fiber composition and size may contribute to development of type 2 diabetes in individuals with LBW. PMID- 17284624 TI - 18F-fluorodeoxyglucose positron emission tomography does not predict malignancy in thyroid nodules cytologically diagnosed as follicular neoplasm. AB - OBJECTIVE: The objective of this study was to evaluate the usefulness of (18)F fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting malignancy in thyroid nodules cytologically diagnosed as follicular neoplasm. PATIENTS AND METHODS: A total of 46 patients with thyroid nodules larger than 1 cm in diameter cytologically diagnosed as follicular neoplasm at Asan Medical Center (Seoul, Korea) were included. FDG-PET images were taken in all patients before surgical resection, and the maximum standardized uptake value (SUVmax) of each nodule was measured. RESULTS: FDG-PET showed hypermetabolic activity of all nodules compared with normal thyroid tissue. Thirty-six patients underwent surgery, whereas 10 refused immediate operation. Fifteen patients had cancer: 11 with follicular and two each with Hurthle cell and follicular variants of papillary cancer. Twenty-one patients had benign nodules: 11 follicular adenomas, eight adenomatous hyperplasias, and two Hurthle cell adenomas. SUVmax did not differ significantly between malignant and benign nodules (3.6 +/- 3.5 vs. 3.4 +/ 3.2; P = 0.83) or among subtypes of benign nodules (P = 0.23). However, SUVmax differed significantly among subtypes of malignant nodules (P = 0.02). CONCLUSIONS: On FDG-PET, the glucose metabolic activities of benign thyroid follicular nodules were as high as those of malignant nodules. These findings suggest that FDG-PET has limited value for selecting candidates for surgery among patients cytologically diagnosed as follicular neoplasm. PMID- 17284625 TI - Gender differences of oligomers and total adiponectin during puberty: a cross sectional study of 859 Danish school children. AB - CONTEXT: Pubertal stages have been shown to influence total adiponectin (ADPN) levels. Furthermore, testosterone has been shown to alter the isomer distribution of ADPN. OBJECTIVE: The goal of this study was to investigate whether pubertal stages and testosterone levels influenced total serum ADPN levels and the distribution of ADPN isomers. DESIGN: This is a cross-sectional study. PATIENTS: The study included 859 children and adolescents (396 males) aged 6-20 yr. MAIN OUTCOME MEASURES: Total ADPN and ADPN isomers were measured using a validated in house immunofluorometric assay. Fractioning of the ADPN into the three major molecular fractions was performed in representative subgroups of pre- and postpubertal males and females (n = 40, 10 in each group) using a validated fast protein liquid chromatography method. RESULTS: Total ADPN levels before puberty were 13.4 (11.1-15.9) mg/liter (median and interquartile range) and 14.7 (12.3 18.1) mg/liter (P = not significant), in males and females, respectively. After puberty, ADPN levels were significantly reduced in males, 9.7 (8.2-12.0) mg/liter but remained unchanged in females, 12.1 (9.7-15.3) mg/liter (P < 0.0001). Concomitantly, a reduction was seen in the ratio of high-molecular-weight (HMW) isomers to total ADPN (HMW ratio) when comparing prepubertal and postpubertal males. Also, postpubertal males had lower HMW ratios than corresponding females (P = 0.038). Finally, a negative correlation was seen between HMW ratio and testosterone (r = -0.430, P = 0.007). CONCLUSION: Serum total ADPN levels decrease through puberty in males. Also, a reduced HMW ratio is seen in males at the onset of puberty. We speculate that the suppression of HMW ADPN may be caused by testosterone. PMID- 17284626 TI - Final height outcome after three years of growth hormone and gonadotropin releasing hormone agonist treatment in short adolescents with relatively early puberty. AB - OBJECTIVE: Our objective was to assess final height (FH) and adverse effects of combined GH and GnRH agonist (GnRHa) treatment in short adolescents born small for gestational age or with normal birth size (idiopathic short stature). DESIGN AND PATIENTS: Thirty-two adolescents with Tanner stage 2-3, age and bone age (BA) less than 12 yr for girls or less than 13 yr for boys, height sd score (SDS) less than -2.0 SDS or between -1.0 and -2.0 SDS plus a predicted adult height (PAH0) less than -2.0 SDS were randomly allocated to receive GH plus GnRHa (n=17) or no treatment (n=15) for 3 yr. FH was assessed at the age of 18 yr or older in girls or 19 yr or older in boys. RESULTS: FH was not different between treatment and control groups. Treated children had a larger height gain (FH-PAH0) than controls: 4.4 (4.9) and -0.5 (6.4) cm, respectively (P<0.05). FH was higher than PAH0 in 76 and 60% of treated and control subjects, respectively. During follow up, 50% of the predicted height gain at treatment withdrawal was lost, resulting in a mean gain of 4.9 cm (range, -4.0 to 12.3 cm) compared with controls. Treatment did not affect body mass index or hip bone mineral density. Mean lumbar spine bone mineral density and bone mineral apparent density tended to be lower in treated boys, albeit statistically not significant. CONCLUSION: Given the expensive and intensive treatment regimen, its modest height gain results, and the possible adverse effect on peak bone mineralization in males, GH plus GnRHa cannot be considered routine treatment for children with idiopathic short stature or persistent short stature after being born small for gestational age. PMID- 17284627 TI - Human adipose tissue cannabinoid receptor 1 gene expression is not related to fat cell function or adiponectin level. AB - CONTEXT: The cannabinoid receptor 1 gene (CNR1) is implicated in adipocyte function. OBJECTIVE: We investigated human adipose tissue CNR1 mRNA in relation to obesity, clinical and metabolic variables, adipocyte function, and adiponectin (ADIPOQ) levels. METHODS: We assessed sc fat biopsies from 96 obese and nonobese subjects and omental fat biopsies from 82 obese and nonobese subjects. RESULTS: The sc and omental adipose CNR1 gene expression were similar in obese and nonobese subjects. No association between either sc or omental adipose CNR1 mRNA levels and body mass index, waist circumference, plasma levels of glucose and insulin, lipids, or blood pressure was found. The sc and omental maximal adrenergic lipolytic activation as well as lipolytic adrenoceptor sensitivity were not related to CNR1 gene expression. Lipogenesis in sc adipocytes also showed no association with CNR1 mRNA levels. Finally, no relation was found between adipose CNR1 gene expression and ADIPOQ mRNA, adipose tissue adiponectin secretion, or circulating adiponectin. CONCLUSION: We found no association of human adipose tissue CNR1 mRNA expression with measures of body fat, metabolic parameters, fat cell function, or ADIPOQ expression. These data do not suggest a major role of human adipose CNR1 in fat cell function or metabolic disease development. PMID- 17284628 TI - Recombinant thyrotropin in the diagnosis of congenital hypothyroidism. AB - CONTEXT: A modern approach to congenital hypothyroidism requires a definitive diagnosis of the underlying mechanisms; this can be achieved within the first weeks of life. When uncertainty persists, treatment is commenced, and the definitive diagnosis of congenital hypothyroidism is deferred to the age of 3 yr. OBJECTIVES: The interruption of thyroid replacement treatment is perceived as risky by parents and physicians. The aim of this pilot study was to test the possibility of a definitive diagnosis during thyroid replacement treatment, using stimulation of thyroid tissue by recombinant human (rh)TSH. SUBJECTS: Eight patients, three boys and five girls, age 5-15 yr (mean, 9.5+/-3.7 yr), with congenital hypothyroidism that had been diagnosed by the neonatal screening program, and having their diagnosis verified between the ages of 3-4 yr, were reevaluated while on thyroid replacement therapy. INTERVENTIONS: Patients received im 0.6 mg/m2 rhTSH on two consecutive days. RESULTS: rhTSH pharmacokinetics, maximal concentration, t1/2, and area under the curve in children were different as compared with adults. In the patients with intact TSH receptors, free T4 levels decreased after the first and the second injection of rhTSH (P=0.0137 and P=0.0149, respectively). All eight children showed identical scintigraphy after rhTSH administration as compared with thyroid replacement withdrawal. CONCLUSIONS: The use of rhTSH is effective for definitive diagnosis of congenital hypothyroidism during thyroid replacement treatment, and no safety issues were encountered. PMID- 17284629 TI - Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial. AB - CONTEXT: The clinical presentation of primary hyperparathyroidism (pHPT) has changed during the last half century, and the diagnosis is now more often made by chance in patients with no specific symptoms. OBJECTIVE: The present study is a randomized, controlled trial that investigates the effects of parathyroidectomy or medical observation in mild asymptomatic pHPT on morbidity and quality of life (QoL). DESIGN/SETTING/PATIENTS: A total of 191 patients (26 men) with asymptomatic pHPT [mean age 64.2 +/- 7.4 (sd) yr] were recruited in the study and randomized to medical observation (serum calcium level 2.69 +/- 0.08 mmol/liter) or surgery (2.70 +/- 0.08 mmol/liter). We here report baseline and 1 (n = 119) and 2 yr data (n = 99) on those who had completed the follow-up visits by the end of the inclusion period. RESULTS: At baseline, the patients had significantly lower QoL (SF-36) and more psychological symptoms, compared with age- and sex matched healthy subjects. The two groups were similar at baseline, and no clinically significant changes in these parameters were seen during the observation time. Calcium and PTH normalized after surgery. The areal bone mineral density increased in the group randomized to operation, whereas the bone mineral density remained stable in the medical observation group. No change in kidney function (creatinine) or blood pressure was observed longitudinally or between the groups. CONCLUSIONS: Asymptomatic patients with mild pHPT have decreased QoL and more psychological symptoms than normal controls. No benefit of operative treatment, compared with medical observation, was found on these measures so far. PMID- 17284631 TI - Impaired sexual and reproductive outcomes in women with classical forms of congenital adrenal hyperplasia. AB - OBJECTIVES: The objectives of the study were 2-fold: 1) a detailed description of sexual and reproductive outcomes in adult women with congenital adrenal hyperplasia (CAH) of different phenotypic severity at birth; and 2) comparisons of these outcomes among CAH subtypes and between CAH women and non-CAH control women. DESIGN: This was a cross-sectional study using a face-to-face interview, a written questionnaire, the Female Sexual Function Index, and a gynecological examination. PATIENTS: Patients included 35 women with CAH, representing Prader stages I-V at birth, aged 18-43 yr, who had been treated from birth to adolescence in the same pediatric endocrine clinics. Sixty-nine non-CAH healthy control women were selected from hospital-staff families. RESULTS: None of the CAH women expressed doubts about their gender assignment. Twenty percent (seven of 35) had homosexual inclinations; 23% (eight of 35) were married; three reported a complete lack of sexual activity; and 37% (13 of 35) said they never had heterosexual intercourse with vaginal penetration. Sexual functioning as assessed by the Female Sexual Function Index was much lower in CAH women than controls and lowest in CAH women with high Prader stages. Eighty-one percent (18 of 22) experienced pain during vaginal penetration. Only eight women became pregnant, and 17% (six of 35) had children. CONCLUSIONS: Despite expert medical and surgical care by physicians dedicated to this rare disease, women with CAH still suffer major limitations in their sexual function and reproductive life. PMID- 17284630 TI - The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. AB - CONTEXT: Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis. OBJECTIVE: We examined whether Se supplementation, during and after pregnancy, influences the thyroidal autoimmune pattern and function. DESIGN: This was a prospective, randomized, placebo controlled study. SETTING: The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology. PATIENTS: A total of 2143 euthyroid pregnant women participated in the study; 7.9% were TPOAb(+). INTERVENTIONS: During pregnancy and the postpartum period, 77 TPOAb(+) women received selenomethionine 200 microg/d (group S1), 74 TPOAb(+) women received placebo (group S0), and 81 TPOAb(-) age-matched women were the control group (group C). MAIN OUTCOME MEASURES: We measured the prevalence of PPTD and hypothyroidism. RESULTS: PPTD and permanent hypothyroidism were significantly lower in group S1 compared with S0 (28.6 vs. 48.6%, P<0.01; and 11.7 vs. 20.3%, P<0.01). CONCLUSION: Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism. PMID- 17284632 TI - Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. AB - CONTEXT: Recently, new methodologies have been applied to commercial immunofluorometric (IFMA) and immunochemiluminometric (ICMA) LH and FSH assays. OBJECTIVE: The objective of the study was to use ICMA to establish basal and GnRH stimulated LH and FSH reference values in normal subjects of different ages and sexual development, compared with IFMA. DESIGN AND METHODS: We established basal and GnRH-stimulated LH and FSH levels of 315 prepubertal and pubertal children (170 males and 145 females) divided into five groups according to Tanner stage. Of these, 106 subjects (59 males and 47 females) were submitted to GnRH test. The prepubertal upper limit of normal for basal LH, determined by the 95th percentiles of the prepubertal population, were 0.2 IU/liter (ICMA) and 0.6 IU/liter (IFMA) in both genders. RESULTS: No overlap of basal LH levels determined by ICMA was observed between prepubertal and pubertal males, but basal LH determined by IFMA overlapped in 11.8% of subjects. In girls, both methods yielded overlapping values (10.4%, ICMA; and 84.6%, IFMA). The LH peak after GnRH stimulation that defined puberty was 4.1 IU/liter (ICMA) and 3.3 IU/liter (IFMA) in boys and 3.3 IU/liter (ICMA) and 4.2 IU/liter (IFMA) in girls. After GnRH stimulation, values determined by the two methods overlapped in both genders. CONCLUSIONS: We conclude that ICMA is more sensitive and precise than IFMA, permitting differentiation of pubertal and prepubertal stage in boys under basal conditions. However, in girls the overlap of basal values was marked, indicating the need for the GnRH test to establish maturity of the hypothalamus-pituitary gonadal axis. PMID- 17284633 TI - Clinical review: Current treatment of malignant pheochromocytoma. AB - CONTEXT: Pheochromocytomas are rare tumors of predominantly adrenal origin that often produce and secrete catecholamines. Malignancy occurs in a variable percentage of cases depending on genetic background and tumor location. Definitive diagnosis relies on the detection of distant metastases. Treatments for malignant pheochromocytoma include surgical debulking, pharmacological control of hormone-mediated symptoms, targeted methods such as external irradiation, and systemic antineoplastic therapy. Different agents and protocols for this purpose are reviewed, and their therapeutic potential is discussed. EVIDENCE ACQUISITION: Literature on antineoplastic therapies for malignant pheochromocytoma was identified by searching the PubMed database with restriction to articles published in English during the past 30 yr. EVIDENCE SYNTHESIS: Because of the rarity of the condition, no randomized clinical trials concerning the treatment of malignant pheochromocytoma have been performed. The strategy established best is [131I]meta-iodobenzylguanidine (MIBG) therapy, which is well tolerated. Similar to cytotoxic chemotherapy with cyclophosphamide, vincristine, and dacarbazine, MIBG can induce remission for a limited period in a significant proportion of patients. Octreotide as a single agent seems to be largely ineffective. CONCLUSIONS: MIBG radiotherapy and cyclophosphamide, vincristine, and dacarbazine chemotherapy are comparable with respect to response rate and toxicity. It is unclear whether combining both can improve the outcome. Future developments may include new multimodal concepts with focus on inhibition of angiogenetic factors and heat shock protein 90. Any present or new therapeutic approach must take into account the highly variable natural course of the disease. PMID- 17284634 TI - Modulation of the homocysteine-betaine relationship by methylenetetrahydrofolate reductase 677 C->t genotypes and B-vitamin status in a large-scale epidemiological study. AB - CONTEXT: Betaine is formed from the essential nutrient choline or is supplied from the diet. It serves as a substrate in the betaine-homocysteine methyltransferase reaction and thereby provides methyl groups for the homocysteine-methionine cycle, which is regulated by enzymes dependent on folate, vitamin B12, riboflavin (vitamin B2), or vitamin B6. OBJECTIVE: We investigated how betaine affected total homocysteine (tHcy) concentration within the frame of variable B-vitamin status and according to the methylenetetrahydrofolate reductase (MTHFR) 677C->T genotype. DESIGN/SETTING/PATIENTS: This is a population based study with a cross-sectional design. It includes 10,601 healthy men and women aged 50-64 yr. OUTCOME MEASURES: Plasma samples were analyzed for tHcy, betaine, choline, dimethylglycine, riboflavin, and vitamin B6, whereas folate and vitamin B12 were analyzed in serum. RESULTS: Betaine was a strong determinant of plasma tHcy in subjects with low serum folate and the MTHFR TT genotype. The association was further strengthened at low levels in the circulation of the other B-vitamins (B2, B6, and B12). Thus, in subjects with the combination of serum folate in the lowest quartile, low vitamin B2, B6, and B12 status, and the MTHFR TT genotype, the difference in tHcy (mean, 95% confidence interval) across extreme plasma betaine quartiles was 8.8 (1.3-16.2) micromol/liter. CONCLUSION: Betaine may thus be an important one-carbon source, particularly in MTHFR 677 TT subjects with inadequate B-vitamin status. PMID- 17284635 TI - Sporadic hyperphosphatasia syndrome featuring periostitis and accelerated skeletal turnover without receptor activator of nuclear factor-kappaB, osteoprotegerin, or sequestosome-1 gene defects. AB - CONTEXT: A middle-aged woman with recent-onset painful swollen fingers and widespread periostitis, elevated serum alkaline phosphatase (ALP) activity and erythrocyte sedimentation rate, and accelerated skeletal turnover was found not to have mutations in the gene sequences for exon 1 of receptor activator of nuclear factor-kappaB (RANK), osteoprotegerin (OPG), or sequestosome-1. INTRODUCTION: Hyperphosphatasia refers to disorders that feature elevated serum ALP activity (hyperphosphatasemia) usually from excesses of the bone isoform of ALP. Such conditions include familial expansile osteolysis, expansile skeletal hyperphosphatasia, and a familial form of early-onset Paget's disease of bone (PDB2), all from constitutive activation of RANK, and juvenile Paget's disease from OPG deficiency. PATIENT AND METHODS: A 38-yr-old woman developed painful swollen fingers and achy bones after an episode of unexplained pericarditis and restrictive lung disease. Sequence analysis of exon 1 of TNFRSF11A encoding RANK, TNFRSF11B encoding OPG, and SQSTM1 encoding sequestosome-1 searched for mutations responsible for familial expansile osteolysis, expansile skeletal hyperphosphatasia, or PDB2, juvenile Paget's disease, or Paget's disease of bone (PDB), respectively. RESULTS: Serum ALP and osteocalcin and urinary hydroxyproline were increased. Radiographs showed widespread, symmetric hyperostosis in the limbs where bone scintigraphy demonstrated enhanced radionuclide uptake. Iliac crest histology revealed accelerated skeletal turnover. No mutations were detected in the three genes examined. Three years of therapy with 70 mg alendronate orally once weekly improved symptoms, radiographic abnormalities, and biochemical markers. CONCLUSIONS: Our patient manifested a unique, sporadic hyperphosphatasia syndrome. Unexplained, transient inflammation seemed to cause her pericarditis, restrictive lung disease, and periostitis with accelerated skeletal turnover that responded well to antiinflammatory drugs and alendronate therapy. PMID- 17284639 TI - Metabolic syndrome: a solution in search of a problem. PMID- 17284636 TI - Adrenal gland volume and dexamethasone-suppressed cortisol correlate with total daily salivary cortisol in African-American women. AB - CONTEXT: Population-based studies of associations between subclinical hypercortisolism and risk for disease states, such as type 2 diabetes mellitus, have been difficult to assess because of imprecise measures of glucocorticoid exposure. Alternative measures (salivary cortisol and adrenal gland volume) have not been systematically compared with 24-h urine free cortisol (UFC) in a healthy population. OBJECTIVE: Our objectives were: 1) to determine whether 24-h UFC and total daily salivary cortisol correlated with each other, adrenal gland volume, and salivary cortisol after dexamethasone suppression and 2) to evaluate the association of adrenal gland volume with salivary cortisol after dexamethasone suppression. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 20 healthy, premenopausal African-American women aged 18-45 yr. MAIN OUTCOME MEASURES: Salivary cortisol was assessed at six time points throughout the day simultaneous with 24-h UFC collection. Adrenal gland volume was measured by computed tomography scan. Dexamethasone-suppressed salivary cortisol was measured at 0800 h after administration of 0.5 mg dexamethasone at 2300 h the prior evening. RESULTS: Dexamethasone-suppressed salivary cortisol levels correlated strongly with individual, timed salivary cortisol measurements, total daily salivary cortisol (rs=0.75; P=0.0001; n=20), and adrenal gland volume (rs=0.66; P=0.004; n=17). Total daily salivary cortisol and adrenal gland volume also correlated (rs=0.46; P=0.04; n=19). In contrast, 24-h UFC levels did not correlate with any of the other hypothalamic-pituitary-adrenal axis measures. CONCLUSION: A dexamethasone suppression test or adrenal gland volume may be alternative measures for characterizing subtle subclinical hypercortisolism in healthy adults. PMID- 17284638 TI - A 10-year, prospective study of the metabolic effects of growth hormone replacement in adults. AB - CONTEXT: Only a few studies have investigated the effects of GH replacement in adults for more than 5 yr. OBJECTIVE/DESIGN/PATIENTS: In a prospective, open label, single-center study, the effects of 10-yr GH replacement were determined. Eighty-seven consecutive patients (52 men and 35 women), with a mean age of 44.1 (range 22-74) yr with adult-onset GH deficiency (GHD) were included. RESULTS: The initial mean dose of GH (0.98 mg/d) was reduced during the study and at yr 10 was 0.47 mg/d. The mean IGF-I sd score increased from -1.81 at baseline to 1.29 at study end. The absolute reduction in total body fat was transient. However, after correction for age and sex using a four-compartment model, the reduction in body fat was sustained during the 10-yr study period. There was a sustained improvement in serum lipid profile and after 10 yr, and blood glycosylated hemoglobin level was reduced. The treatment responses in IGF-I sd score, serum high-density lipoprotein cholesterol level, and body composition as measured using dual-energy x-ray absorptiometry were more marked in men, whereas women had a more marked reduction in blood glycosylated hemoglobin level. CONCLUSION: The effect on the absolute amount of body fat was seen early and was transient, which could be due to the normal aging of the patients. The effects on metabolic indices were detected later, but they were sustained and even progressive throughout the study period. PMID- 17284637 TI - Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects. AB - CONTEXT: An oral formulation of EP01572, a peptidomimetic growth hormone secretagogue, was studied. An oral delivery system would be preferable in many of the possible therapeutic indications of ghrelin agonists such as EP01572. OBJECTIVES: Our objective was to establish the pharmacological profile and the GH releasing activity of increasing oral doses of EP01572 in healthy volunteers. In addition, the pharmacokinetics and pharmacological effects of EP01572 were investigated after intraduodenal (ID) administration. SETTING: This study was a single-center escalating dose study with oral and ID applications. SUBJECTS AND METHODS: In the first part, EP01572 was given orally to 36 male subjects; the treatment consisted of one oral dose of either EP01572 or placebo (0.005, 0.05, and 0.5 mg/kg body weight). Six subjects received two additional oral doses of EP01572: 0.125 and 0.25 mg/kg body weight. In the second part, the following treatments were performed in a randomized order: 1) administration of a bolus of saline (placebo) to the small intestine; 2) ID administration of a bolus of EP01572 at 0.2 mg/kg body weight; 3) ID perfusion of a bolus of EP01572 at 0.35 mg/kg body weight; and 4) ID perfusion of a bolus of EP01572 at 0.5 mg/kg body weight. RESULTS: The oral and ID administration of EP01572 induced a rapid and dose-dependent increase in plasma drug concentrations and a potent GH release in healthy male volunteers. CONCLUSIONS: This study showed that EP01572 was active with regard to stimulation of GH release in humans after oral and ID administration. PMID- 17284640 TI - Metabolic syndrome: a multiplex cardiovascular risk factor. AB - CONTEXT: The metabolic syndrome (MetS) is a multiplex risk factor for cardiovascular disease. The syndrome develops through interplay of obesity and metabolic susceptibility. OBJECTIVE: This article addresses whether the MetS construct has clinical utility. POSITION: The National Cholesterol Education Program and other organizations have proposed that the MetS can be recognized clinically by a clustering of simple clinical measures including waist circumferences, blood pressure, triglycerides, high-density lipoproteins, and glucose. People with this clustering have most or all of the components of the MetS. Identifying the MetS has several advantages. It discovers persons who are at increased risk for cardiovascular disease. A diagnosis focuses more clinical attention on the underlying causes, notably obesity and other lifestyle factors; it thereby reinforces the utility of lifestyle changes in clinical practice. A diagnosis further informs physicians on choice and intensity of drug therapy for elevated cholesterol, aspirin prophylaxis, and blood pressure and glucose control. The introduction of the MetS has led to a large number of epidemiological, metabolic, and genetic studies that have heightened our understanding of the condition's prevalence and pathogenesis. It has been a stimulus to the development of new drugs or drug combinations that will modify multiple risk factors simultaneously. CONCLUSIONS: This author holds that the MetS counts as a multiplex cardiovascular risk factor that is clinically useful and will lead to advances in diagnosis and treatment of an important cause of cardiovascular disease. PMID- 17284641 TI - Commentary: Guideline for male testosterone therapy: a regulatory perspective. PMID- 17284642 TI - Commentary: Guideline for male testosterone therapy: a clinician's perspective. PMID- 17284643 TI - Commentary: Guideline for male testosterone therapy: a European perspective. PMID- 17284644 TI - Editorial: Megestrol acetate use for weight gain should be carefully considered. PMID- 17284645 TI - Editorial: School-based intervention to reduce obesity and diabetes risks: small steps for a big problem. PMID- 17284646 TI - Editorial: Calcitonin determination in patients with nodular thyroid disease. PMID- 17284647 TI - Editorial: Smoking and the skeleton. PMID- 17284648 TI - Vircell assays for detection of antibodies against Legionella pneumophila. PMID- 17284649 TI - Leukemia inhibitory factor influences the fate choice of mesenchymal progenitor cells. AB - Osteoblasts and adipocytes derive from a common mesenchymal precursor, and in at least some circumstances, differentiation along these two lineages is inversely related. For example, we have recently observed that concomitant with inhibition of osteoblast differentiation and bone nodule formation, leukemia inhibitory factor (LIF) induces genes regulating lipid metabolism in fetal rat calvaria (RC) cell cultures. In this study, we further investigated the adipogenic capacity of LIF-treated RC cells. Quantitative analyses revealed that LIF increased the adipocyte differentiation induced by the peroxisome proliferator-activated receptor gamma agonist BRL49653 (BRL) in RC cell populations. Gene expression profiling of individual RC cell colonies in untreated cells or cells treated with LIF, BRL, or combined LIF-BRL suggested that some adipocytes arose from bipotential or other primitive precursors, including osteoprogenitors, since many colonies co-expressed osteoblast and adipocyte differentiation markers, whereas some arose from other cell pools, most likely committed preadipocytes present in the population. These analyses further suggested that LIF and BRL do not act at the same stages of the mesenchymal hierarchy, but rather that LIF modifies differentiation of precursor cells, whereas BRL acts later to favor adipocyte differentiation. Taken together, our data suggest that LIF increased adipocyte differentiation at least in part by altering the fate of osteoblastic cells and their precursors. PMID- 17284650 TI - Allogeneic intrabone marrow-bone marrow transplantation plus donor lymphocyte infusion suppresses growth of colon cancer cells implanted in skin and liver of rats. AB - We have recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) + donor lymphocyte infusion (DLI) using CD4(+) cell depleted spleen cells (CD4(-) cells) can prevent graft-versus-host disease (GvHD) but suppress tumor growth (Meth A: fibrosarcoma) in mice. In the present study, we show that allogeneic IBM-BMT + DLI using CD4(-) cells also has suppressive effects on the growth of colon cancer cells implanted not only in the skin but also in the liver of rats. First, we examined the effects of allogeneic IBM-BMT + DLI on the subcutaneously inoculated ACL-15 (rat colon cancer cell line). Lethally irradiated Fischer rats (F344 rats) were transplanted with T-cell depleted bone marrow cells (BMCs) from Brown Norway (BN) rats. Simultaneously, DLI was performed using whole spleen cells (whole cells), CD4(+) cell-depleted spleen cells (CD4(-) cells) or CD8(+) cell-depleted spleen cells (CD8(-) cells) of BN rats. Although allogeneic IBM-BMT + DLI suppressed tumor growth, a considerable number of rats treated with allogeneic IBM-BMT + DLI using whole cells or CD8(-) cells died due to GvHD. In contrast, allogeneic IBM-BMT + DLI using CD4(-) cells also suppressed tumor growth, but there was no GvHD. Based on these findings, we next examined the effects of allogeneic IBM-BMT + DLI using CD4(-) cells on the cancer cells implanted in the liver. Allogeneic IBM-BMT + DLI using CD4(-) cells via the portal vein significantly prolonged the survival. These results suggest that allogeneic IBM-BMT + DLI using CD4(-) cells could become a new strategy for the treatment of solid tumors. PMID- 17284651 TI - Qualification of embryonal carcinoma 2102Ep as a reference for human embryonic stem cell research. AB - As the number of human embryonic stem cell (hESC) lines increases, so does the need for systematic evaluation of each line's characteristics and potential. Comparisons between lines are complicated by variations in culture conditions, feeders, spontaneous differentiation, and the absence of standardized assays. These difficulties, combined with the inability of most labs to maintain more than a few lines simultaneously, compel the development of reference standards to which hESC lines can be compared. The use of a stable cell line as a reference standard offers many advantages. A line with a relatively unchanging hESC-like gene and protein expression pattern could be a positive control for developing assays. It can be used as a reference for genomics or proteomics studies, especially for normalizing results obtained in separate laboratories. Such a cell line should be widely available without intellectual property restraints, easily cultured without feeders, and resistant to spontaneous changes in phenotype. We propose that the embryonal carcinoma (EC) line 2102Ep meets these requirements. We compared the protein, gene, and microRNA expression of this cell line with those of hESC lines and alternative reference lines such as the EC line NTERA-2 and the karyotypically abnormal hESC line BG01V. The overall expression profiles of all these lines were similar, with exceptions reflecting the germ cell origins of EC. On the basis of global gene and microRNA expression, 2102Ep is somewhat less similar to hESC than the alternatives; however, 2102Ep expresses more hESC associated microRNAs than NTERA-2 does, and fewer markers of differentiated fates. PMID- 17284652 TI - Differentiating human embryonic stem cells express a unique housekeeping gene signature. AB - Housekeeping genes (HKGs) are involved in basic functions needed for the sustenance of the cell and are assumed to be constitutively expressed at a constant level. Based on these features, HKGs are frequently used for normalization of gene expression data. In the present study, we used the CodeLink Gene Expression Bioarray system to interrogate changes in gene expression occurring during differentiation of human ESCs (hESCs). Notably, in the three hESC lines used for the study, we observed that the RNA levels of 56 frequently used HKGs varied to a degree that rendered them inappropriate as reference genes. Therefore, we defined a novel set of HKGs specifically for hESCs. Here we present a comprehensive list of 292 genes that are stably expressed (coefficient of variation <20%) in differentiating hESCs. These genes were further grouped into high-, medium-, and low-expressed genes. The expression patterns of these novel HKGs show very little overlap with results obtained from somatic cells and tissues. We further explored the stability of this novel set of HKGs in independent, publicly available gene expression data from hESCs and observed substantial similarities with our results. Gene expression was confirmed by real time quantitative polymerase chain reaction analysis. Taken together, these results suggest that differentiating hESCs have a unique HKG signature and underscore the necessity to validate the expression profiles of putative HKGs. In addition, this novel set of HKGs can preferentially be used as controls in gene expression analyses of differentiating hESCs. PMID- 17284653 TI - Differential requirements for hematopoietic commitment between human and rhesus embryonic stem cells. AB - Progress toward clinical application of ESC-derived hematopoietic cellular transplantation will require rigorous evaluation in a large animal allogeneic model. However, in contrast to human ESCs (hESCs), efforts to induce conclusive hematopoietic differentiation from rhesus macaque ESCs (rESCs) have been unsuccessful. Characterizing these poorly understood functional differences will facilitate progress in this area and likely clarify the critical steps involved in the hematopoietic differentiation of ESCs. To accomplish this goal, we compared the hematopoietic differentiation of hESCs with that of rESCs in both EB culture and stroma coculture. Initially, undifferentiated rESCs and hESCs were adapted to growth on Matrigel without a change in their phenotype or karyotype. Subsequent differentiation of rESCs in OP9 stroma led to the development of CD34(+)CD45(-) cells that gave rise to endothelial cell networks in methylcellulose culture. In the same conditions, hESCs exhibited convincing hematopoietic differentiation. In cytokine-supplemented EB culture, rESCs demonstrated improved hematopoietic differentiation with higher levels of CD34(+) and detectable levels of CD45(+) cells. However, these levels remained dramatically lower than those for hESCs in identical culture conditions. Subsequent plating of cytokine-supplemented rhesus EBs in methylcellulose culture led to the formation of mixed colonies of erythroid, myeloid, and endothelial cells, confirming the existence of bipotential hematoendothelial progenitors in the cytokine-supplemented EB cultures. Evaluation of four different rESC lines confirmed the validity of these disparities. Although rESCs have the potential for hematopoietic differentiation, they exhibit a pause at the hemangioblast stage of hematopoietic development in culture conditions developed for hESCs. PMID- 17284654 TI - Exercise-induced hemolysis is caused by protein modification and most evident during the early phase of an ultraendurance race. AB - Whether structural changes of the erythrocyte membrane increase the susceptibility to hemolysis particularly of the relatively older cell population during the early phase of a 216-km ultrarace was tested in six male runners (age 53.6 +/- 10.4 yr, height 175.8 +/- 11.1 cm, body mass 75.9 +/- 8.4 kg). Erythrocyte membrane spectrins were lowest (P < 0.001) after 42 km (75.59 +/- 5.25% of prerace) and increased (P < 0.001) toward 216 km (88.27 +/- 3.37%). Susceptibility to osmotic hemolysis was highest (P < 0.01) after 42 km (107.34 +/ 3.02 mOsm sodium phosphate buffer) with almost identical (P > 0.05) values prerace (97.98 +/- 3.41 mOsm) and postrace (98.61 +/- 3.26 mOsm). Haptoglobin indicated intravascular hemolysis of 9.27 x 10(9) cells/l (P < 0.05) during the initial 84 km. Changes in hematocrit and plasma proteins indicated an estimated total net erythrocyte loss of 3.47 x 10(11) cells/l (P < 0.05) after 21 km. This was compensated by a gain in erythrocytes (P < 0.05) of 3.31 x 10(11) cells/l during the final 132 km. A main effect (P < 0.05) on erythropoietin suggests increased erythropoiesis throughout the race. Exercise-induced hemolysis reflects alterations in erythrocyte membrane spectrins and occurs particularly in the early phase of an ultraendurance race because of a relative older cell population. PMID- 17284655 TI - Counterpoint: Interleukin-6 does not have a beneficial role in insulin sensitivity and glucose homeostasis. PMID- 17284658 TI - Point:counterpoint: Interleukin-6 does/does not have a beneficial role in insulin sensitivity and glucose homeostasis. PMID- 17284659 TI - Point:counterpoint: Increased mechanoreceptor/metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure. PMID- 17284661 TI - Plasma volume expansion does not influence oxygen uptake kinetics in trained cyclists. PMID- 17284663 TI - Distinct roles of fibroblast growth factor receptor 1 and 2 in regulating cell survival and epithelial-mesenchymal transition. AB - Two related receptor tyrosine kinases (RTKs), fibroblast growth factor receptor 1 and 2 (FGFR1 and FGFR2), exert distinct effects during carcinogenesis. To examine FGFR1 and FGFR2 signaling in polarized epithelia, we have developed an in vitro three-dimensional HC11 mouse mammary epithelial cell culture model combined with a chemically inducible FGFR (iFGFR) dimerization system. Although activation of both RTKs led to reinitiation of cell proliferation and loss of cell polarity, only iFGFR1 activation induced cell survival and epithelial to mesenchymal transition. In contrast, iFGFR2 activation induced cell apoptosis even in the cells in direct contact with the extracellular matrix. Activation of iFGFR2, but not iFGFR1, led to rapid receptor down-regulation and transient activation of downstream signaling, which were partially rescued by Cbl small interfering RNA knockdown or the proteasome inhibitor lactacystin. Importantly, inhibition of proteasome activity in iFGFR2-activated structures led to epithelial to mesenchymal transition and invasive phenotypes resembling those observed after iFGFR1 activation. These studies demonstrate, for the first time, that the duration of downstream signaling determines the distinct phenotypes mediated by very homologous RTKs in three-dimensional cultures. PMID- 17284664 TI - Coregulators: from whence came these "master genes". PMID- 17284665 TI - A critical region in the mineralocorticoid receptor for aldosterone binding and activation by cortisol: evidence for a common mechanism governing ligand binding specificity in steroid hormone receptors. AB - The amino acids that confer aldosterone binding specificity to the mineralocorticoid receptor (MR) remain to be determined. We had previously analyzed a panel of chimeras created between the MR and the glucocorticoid receptor and determined that amino acids 804-874 of the MR ligand binding domain are critical for aldosterone binding. In the present study a further series of chimeras was created within this region. The chimeras were analyzed by a transactivation assay and [(3)H]aldosterone binding, and the critical region was narrowed down to amino acids 820-844. Site-directed mutagenesis was used to create single and multiple amino acid substitutions in this region. These studies identified 12 of the 16 amino acids that differ in the MR and the glucocorticoid receptor in this region as being critical to conferring aldosterone responsivity. The amino acids that differ in the region 820-844 lie on the surface of the molecule and, therefore, it appears that MR ligand binding selectivity is conferred by residues that do not form part of the ligand binding pocket. Other studies have found that the corresponding regions of the androgen and glucocorticoid receptors are critical for the binding of natural and synthetic ligands, suggesting a common mechanism governing ligand binding specificity. The new chimeras also displayed, as previously reported, a dissociation between cortisol binding and transactivation and, intriguingly, only those that bound aldosterone with high affinity were activated by cortisol, suggesting a common mechanism that underlies specificity of aldosterone binding and the ability of cortisol to activate the MR. PMID- 17284666 TI - Circadian profiling of the transcriptome in NIH/3T3 fibroblasts: comparison with rhythmic gene expression in SCN2.2 cells and the rat SCN. AB - To screen for output signals that may distinguish the pacemaker in the mammalian suprachiasmatic nucleus (SCN) from peripheral-type oscillators in which the canonical clockworks are similarly regulated in a circadian manner, the rhythmic behavior of the transcriptome in forskolin-stimulated NIH/3T3 fibroblasts was analyzed and compared relative to SCN2.2 cells in vitro and the rat SCN. Similar to the circadian profiling of the SCN2.2 and rat SCN transcriptomes, NIH/3T3 fibroblasts exhibited circadian fluctuations in the expression of the core clock genes, Per2, Cry1, and Bmal1, and 323 functionally diverse transcripts, many of which regulate cellular communication. Overlap in rhythmic transcripts among NIH/3T3 fibroblasts, SCN2.2 cells, and the rat SCN was limited to these clock genes and four other genes that mediate fatty acid and lipid metabolism or function as nuclear factors. Compared with NIH/3T3 cells, circadian gene expression in SCN oscillators was more prevalent among genes mediating glucose metabolism and neurotransmission. Coupled with evidence for the rhythmic regulation of the inducible isoform of nitric oxide synthase (iNos) in SCN2.2 cells and the rat SCN but not in fibroblasts, studies examining the effects of a NOS inhibitor on metabolic rhythms in cocultures containing SCN2.2 cells and untreated NIH/3T3 cells suggest that the gaseous neurotransmitter nitric oxide may play a key role in SCN pacemaker function. This comparative analysis of circadian gene expression in SCN and non-SCN cells may have important implications in the selective analysis of circadian signals involved in the coupling of SCN oscillators and regulation of rhythmicity in downstream cells. PMID- 17284667 TI - Drosophila dMRP4 regulates responsiveness to O2 deprivation and development under hypoxia. AB - For most vertebrates, oxygen is a prerequisite for survival. Although we have previously shown that Drosophila melanogaster is hypoxia tolerant, how this species senses O(2) deprivation and how it survives oxygen-limiting conditions are as yet poorly understood. We began to address this question by testing for anoxic responsiveness in Drosophila adult flies following overexpression of existing EP lines. In this screen, we identified Drosophila CG14709 gene as a homolog of the human multidrug resistance protein 4 (MRP4/ABCC4) that is tightly regulated to oxygen. Ubiquitous expression of dMRP4 in adult flies resulted in increased sensitivity to anoxia as they had longer recovery time from anoxic stupor. When exposed to 4% oxygen chronically (throughout its lifespan), constitutive expression of dMRP4 in larvae caused larval lethality due to growth arrest. Mutations of dMRP4 led to a hypersensitive response to acute anoxia in adult flies but had less impact on larval survival under chronic hypoxia compared with dMRP4 overexpression. Selective expression of this gene in neurons, but not in glia or muscles, mirrored the same phenotype as the ubiquitous one. Thus, our data suggest novel roles for MRP in vivo: 1) dMRP4 regulates the sensitivity to acute or chronic O(2) deprivation, and 2) dMRP expression in neurons is sufficient to induce the sensitivity to O(2) in the whole organism. PMID- 17284668 TI - Alterations in soleus muscle gene expression associated with a metabolic endpoint following exercise training by lean and obese Zucker rats. AB - Exercise training decreases insulin resistance and increases glucose tolerance in conditions of prediabetes and overt Type 2 diabetes. However, the adaptive responses in skeletal muscle at the molecular and genetic level for these effects of exercise training have not been clearly established in an animal model of prediabetes. The present study identifies alterations in muscle gene expression that occur with exercise training in prediabetic, insulin-resistant obese Zucker rats and insulin-sensitive lean Zucker rats and are associated with a well defined metabolic outcome. Treadmill running for up to 4 wk caused significant enhancements of glucose tolerance as assessed by the integrated area under the curve for glucose (AUCg) during an oral glucose tolerance test. Using microarray analysis, we identified a set of only 12 genes as both significantly altered by exercise training (>1.5-fold change; P < 0.05) and significantly correlated (P < 0.05) with the AUCg. Two genes, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) and protein kinase C-zeta (PKC-zeta), are involved in the regulation of muscle glucose transport, and we provide the first evidence that PKC-zeta gene expression is enhanced by exercise training in insulin-resistant muscle. Protein expression of PGC-1alpha and PKC-zeta were positively correlated with the mRNA expression for these two genes. Overall, we have identified a limited number of genes in soleus muscle of lean and obese Zucker rats that are associated with both decreased insulin resistance and increased glucose tolerance following endurance exercise training. These findings could guide the development of pharmaceutical "exercise mimetics" in the treatment of insulin-resistant, prediabetic, or Type 2 diabetic individuals. PMID- 17284669 TI - Identification of reference genes for quantitative real-time PCR in the bovine mammary gland during the lactation cycle. AB - Achieving greater understanding of the genomic influence on milk synthesis in dairy cows represents a daunting challenge. Bovine-specific microarrays have allowed for high-throughput gene expression analysis of the mammary transcriptome. However, real-time PCR (qPCR) still represents the method of choice for accurate expression profiling of small numbers of genes and verification of key microarray relationships. This method is extremely sensitive but requires data normalization to account for analytical errors. Ideally, expression of genes used as internal controls should not be affected by specific treatments or physiological state. Mammary biopsies were collected from five cows each at -15, 1, 15, 30, 60, 120, and 240 days relative to parturition for gene expression profiling. We evaluated expression of nine genes (RPS9, ACTB, GAPD, GTP, ITGB4BP, MRPL39, RPS23, RPS15, and UXT) that could serve as internal controls in mammary tissue using qPCR. Due to gradual increases in mammary RNA concentration (mug/mg tissue) over lactation, all genes investigated experienced a dilution effect. We used pairwise comparison of expression ratios to analyze the reliability of these genes as internal controls. UXT, RPS9, and RPS15 had the most stable expression ratios across cow and time. We also assessed co-regulation among genes through network analysis. Network analysis suggested co-regulation among most of the genes examined, with MYC playing a central role. Pairwise comparison was suitable for finding appropriate internal controls in mammary gland tissue. Results showed that the geometrical average of UXT, RPS9, and RPS15 expression could be used as internal control for longitudinal mammary gene expression profiling. PMID- 17284670 TI - The in vitro and in vivo cardiovascular effects of Delta9-tetrahydrocannabinol in rats made hypertensive by chronic inhibition of nitric-oxide synthase. AB - Evidence suggests that Delta9-tetrahydrocannabinol (THC) may have antihypertensive effects and that the vasodilator effect of endocannabinoids is enhanced in rats made hypertensive by chronic NO synthase inhibition. Therefore, the aims of the present study were to investigate whether the in vitro and in vivo cardiovascular responses to THC are altered by Nomega-nitro-L-arginine methyl ester (L-NAME) treatment. The vasorelaxant effects of THC were enhanced in small mesenteric arteries from L-NAME-treated rats. This enhanced response was not inhibited by cannabinoid CB1 receptor antagonism [1 microM N-(piperidin-1-yl) 5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; AM251]. Pretreating vessels with the transient receptor potential vanilloid receptor receptor agonist capsaicin at 10 microM for 1 h reduced vasorelaxation to THC to a greater extent in L-NAME-treated than control rats. Inhibition of cyclooxygenase with 10 microM indomethacin inhibited THC responses in arteries from L-NAME-treated rats but not from control rats. In conscious, chronically instrumented rats, 1 mg kg-1 i.v. THC caused a pressor effect, with vasoconstriction of the renal and mesenteric vascular beds, and hindquarters vasodilatation. Pretreatment with 3 mg kg-1 i.v. AM251 reduced the pressor and vasoconstrictor effects of THC, abolished the hindquarters vasodilatation, and revealed a bradycardic response. L-NAME-treated rats showed similar pressor and vasoconstrictor responses to THC, but with bradycardia, and reduced hindquarter vasodilatation. These data show that, in vitro, isolated arteries of L-NAME treated rats show enhanced vasorelaxant responses to THC through an increased sensory nerve component and stimulation of prostanoids. However, in vivo, THC causes a CB1 receptor-mediated pressor effect with hindquarters vasodilatation. There was no evidence of enhanced vasodilator effects of THC in L-NAME-treated animals in vivo. PMID- 17284671 TI - Functional adenylyl cyclase inhibition in murine cardiomyocytes by 2'(3')-O-(N methylanthraniloyl)-guanosine 5'-[gamma-thio]triphosphate. AB - Beta1-adrenergic receptor activation stimulates cardiac L-type Ca2+ channels via adenylyl cyclases (ACs), with AC5 and AC6 being the most important cardiac isoforms. Recently, we have identified 2'(3')-O-(N-methylanthraniloyl)-guanosine 5'-[gamma-thio-]triphosphate (MANT-GTPgammaS) as a potent competitive AC inhibitor. Intriguingly, MANT-GTPgammaS inhibits AC5 and -6 more potently than other cyclases. These data prompted us to study the effects of MANT-GTPgammaS on L-type Ca2+ currents (ICa,L) in ventricular myocytes of wild-type (WT) and AC5 deficient (AC5-/-) mice by whole-cell recordings. In wild-type myocytes, MANT GTPgammaS attenuated ICa,L stimulation following isoproterenol application in a concentration-dependent manner (control, +77+/-13%; 100 nM MANT-GTPgammaS, +43+/ 6%; 1 microM MANT-GTPgammaS, +21+/-9%; p<0.05). The leftward shift of current voltage curves was abolished by 1 microM but not by 100 nM MANT-GTPgammaS. In myocytes from AC5-/- mice, the residual stimulation of ICa,L was not further attenuated by the nucleotide, indicating AC5 to be the major AC isoform mediating acute beta-adrenergic stimulation in WT mice. Interestingly, basal ICa,L was lowered by 1 microM but not by 100 nM MANT-GTPgammaS. The decrease was less pronounced in myocytes from AC5-/- mice compared with wild types (-23+/-1 versus 40+/-7%), indicating basal ICa,L to be partly driven by AC5. Collectively, we found a concentration-dependent inhibition of ICa,L by MANT-GTPgammaS, both under basal conditions and following beta-adrenergic stimulation. Comparison of data from wild-type and AC5-deficient mice indicates that AC5 plays a major role in ICa,L activation and that MANT-GTPgammaS predominantly acts via AC5 inhibition. PMID- 17284673 TI - Canid genomics: mapping genes for behavior in the silver fox. PMID- 17284672 TI - AT-rich repeats associated with chromosome 22q11.2 rearrangement disorders shape human genome architecture on Yq12. AB - Low copy repeats (LCRs; segmental duplications) constitute approximately 5% of the sequenced human genome. Nonallelic homologous recombination events between LCRs during meiosis can lead to chromosomal rearrangements responsible for many genomic disorders. The 22q11.2 region is susceptible to recurrent and nonrecurrent deletions, duplications as well as translocations that are mediated by LCRs termed LCR22s. One particular DNA structural element, a palindromic AT rich repeat (PATRR) present within LCR22-3a, is responsible for translocations. Similar AT-rich repeats are present within the two largest LCR22s, LCR22-2 and LCR22-4. We provide direct sequence evidence that the AT-rich repeats have altered LCR22 organization during primate evolution. The AT-rich repeats are surrounded by a subtype of human satellite I (HSAT I), and an AluSc element, forming a 2.4-kb tripartite structure. Besides 22q11.2, FISH and PCR mapping localized the tripartite repeat within heterochromatic, unsequenced regions of the genome, including the pericentromeric regions of the acrocentric chromosomes and the heterochromatic portion of Yq12 in humans. The repeat is also present on autosomes but not on chromosome Y in other hominoid species, suggesting that it has duplicated on Yq12 after speciation of humans from its common ancestor. This demonstrates that AT-rich repeats have shaped or altered the structure of the genome during evolution. PMID- 17284674 TI - Identification of muscle-specific regulatory modules in Caenorhabditis elegans. AB - Transcriptional regulation is the major regulatory mechanism that controls the spatial and temporal expression of genes during development. This is carried out by transcription factors (TFs), which recognize and bind to their cognate binding sites. Recent studies suggest a modular organization of TF-binding sites, in which clusters of transcription-factor binding sites cooperate in the regulation of downstream gene expression. In this study, we report our computational identification and experimental verification of muscle-specific cis-regulatory modules in Caenorhabditis elegans. We first identified a set of motifs that are correlated with muscle-specific gene expression. We then predicted muscle specific regulatory modules based on clusters of those motifs with characteristics similar to a collection of well-studied modules in other species. The method correctly identifies 88% of the experimentally characterized modules with a positive predictive value of at least 65%. The prediction accuracy of muscle-specific expression on an independent test set is highly significant (P<0.0001). We performed in vivo experimental tests of 12 predicted modules, and 10 of those drive muscle-specific gene expression. These results suggest that our method is highly accurate in identifying functional sequences important for muscle-specific gene expression and is a valuable tool for guiding experimental designs. PMID- 17284675 TI - mtDNA phylogeny and evolution of laboratory mouse strains. AB - Inbred mouse strains have been maintained for more than 100 years, and they are thought to be a mixture of four different mouse subspecies. Although genealogies have been established, female inbred mouse phylogenies remain unexplored. By a phylogenetic analysis of newly generated complete mitochondrial DNA sequence data in 16 strains, we show here that all common inbred strains descend from the same Mus musculus domesticus female wild ancestor, and suggest that they present a different mitochondrial evolutionary process than their wild relatives with a faster accumulation of replacement substitutions. Our data complement forthcoming results on resequencing of a group of priority strains, and they follow recent efforts of the Mouse Phenome Project to collect and make publicly available information on various strains. PMID- 17284676 TI - A meiotic linkage map of the silver fox, aligned and compared to the canine genome. AB - A meiotic linkage map is essential for mapping traits of interest and is often the first step toward understanding a cryptic genome. Specific strains of silver fox (a variant of the red fox, Vulpes vulpes), which segregate behavioral and morphological phenotypes, create a need for such a map. One such strain, selected for docility, exhibits friendly dog-like responses to humans, in contrast to another strain selected for aggression. Development of a fox map is facilitated by the known cytogenetic homologies between the dog and fox, and by the availability of high resolution canine genome maps and sequence data. Furthermore, the high genomic sequence identity between dog and fox allows adaptation of canine microsatellites for genotyping and meiotic mapping in foxes. Using 320 such markers, we have constructed the first meiotic linkage map of the fox genome. The resulting sex-averaged map covers 16 fox autosomes and the X chromosome with an average inter-marker distance of 7.5 cM. The total map length corresponds to 1480.2 cM. From comparison of sex-averaged meiotic linkage maps of the fox and dog genomes, suppression of recombination in pericentromeric regions of the metacentric fox chromosomes was apparent, relative to the corresponding segments of acrocentric dog chromosomes. Alignment of the fox meiotic map against the 7.6x canine genome sequence revealed high conservation of marker order between homologous regions of the two species. The fox meiotic map provides a critical tool for genetic studies in foxes and identification of genetic loci and genes implicated in fox domestication. PMID- 17284677 TI - Improvement of whole-genome annotation of cereals through comparative analyses. AB - Rice is an important model species for the Poaceae and other monocotyledonous plants. With the availability of a near-complete, finished, and annotated rice genome, we performed genome level comparisons between rice and all plant species in which large genomic or transcriptomic data sets are available to determine the utility of cross-species sequence for structural and functional annotation of the rice genome. Through comparative analyses with four plant genome sequence data sets and transcript assemblies from 185 plant species, we were able to confirm and improve the structural annotation of the rice genome. Support for 38,109 (89.3%) of the total 42,653 nontransposable element-related genes in the rice genome in the form of a rice expressed sequence tag, full-length cDNA, or plant homolog from our comparative analyses could be found. Although the majority of the putative homologs were obtained from Poaceae species, putative homologs were identified in dicotyledonous angiosperms, gymnosperms, and other plants such as algae, moss, and fern. A set of rice genes (7669) lacking a putative homolog was identified which may be lineage-specific genes that evolved after speciation and have a role in species diversity. Improvements to the current rice gene structural annotation could be identified from our comparative alignments and we were able to identify 487 genes which were mostly likely missed in the current rice genome annotation and another 500 genes for structural annotation review. We were able to demonstrate the utility of cross-species comparative alignments in the identification of noncoding sequences and in confirmation of gene nesting in rice. PMID- 17284679 TI - Identification of novel peptide hormones in the human proteome by hidden Markov model screening. AB - Peptide hormones are small, processed, and secreted peptides that signal via membrane receptors and play critical roles in normal and pathological physiology. The search for novel peptide hormones has been hampered by their small size, low or restricted expression, and lack of sequence similarity. To overcome these difficulties, we developed a bioinformatics search tool based on the hidden Markov model formalism that uses several peptide hormone sequence features to estimate the likelihood that a protein contains a processed and secreted peptide of this class. Application of this tool to an alignment of mammalian proteomes ranked 90% of known peptide hormones among the top 300 proteins. An analysis of the top scoring hypothetical and poorly annotated human proteins identified two novel candidate peptide hormones. Biochemical analysis of the two candidates, which we called spexin and augurin, showed that both were localized to secretory granules in a transfected pancreatic cell line and were recovered from the cell supernatant. Spexin was expressed in the submucosal layer of the mouse esophagus and stomach, and a predicted peptide from the spexin precursor induced muscle contraction in a rat stomach explant assay. Augurin was specifically expressed in mouse endocrine tissues, including pituitary and adrenal gland, choroid plexus, and the atrio-ventricular node of the heart. Our findings demonstrate the utility of a bioinformatics approach to identify novel biologically active peptides. Peptide hormones and their receptors are important diagnostic and therapeutic targets, and our results suggest that spexin and augurin are novel peptide hormones likely to be involved in physiological homeostasis. PMID- 17284680 TI - C5a receptor expression in T lymphocytes. PMID- 17284678 TI - Sequencing and analysis of chromosome 1 of Eimeria tenella reveals a unique segmental organization. AB - Eimeria tenella is an intracellular protozoan parasite that infects the intestinal tracts of domestic fowl and causes coccidiosis, a serious and sometimes lethal enteritis. Eimeria falls in the same phylum (Apicomplexa) as several human and animal parasites such as Cryptosporidium, Toxoplasma, and the malaria parasite, Plasmodium. Here we report the sequencing and analysis of the first chromosome of E. tenella, a chromosome believed to carry loci associated with drug resistance and known to differ between virulent and attenuated strains of the parasite. The chromosome--which appears to be representative of the genome -is gene-dense and rich in simple-sequence repeats, many of which appear to give rise to repetitive amino acid tracts in the predicted proteins. Most striking is the segmentation of the chromosome into repeat-rich regions peppered with transposon-like elements and telomere-like repeats, alternating with repeat-free regions. Predicted genes differ in character between the two types of segment, and the repeat-rich regions appear to be associated with strain-to-strain variation. PMID- 17284682 TI - The cover. Le silence. PMID- 17284683 TI - A piece of my mind. The importance of the right heart. PMID- 17284684 TI - Cognitive-behavioral therapy shows promise for children with mental illness. PMID- 17284681 TI - (S)-armepavine inhibits human peripheral blood mononuclear cell activation by regulating Itk and PLCgamma activation in a PI-3K-dependent manner. AB - Chinese herbs are useful edible and medicinal plants for their immune modulatory functions. We have proven that (S)-armepavine (C19H23O3N; MW313) from Nelumbo nucifera inhibits the proliferation of human PBMCs activated with PHA and improves autoimmune diseases in MRL/MpJ-lpr/lpr mice. In the present study, the pharmacological activities of (S)-armepavine were evaluated in PHA-activated PBMCs. The results showed that (S)-armepavine suppressed PHA-induced PBMC proliferation and genes expression of IL-2 and IFN-gamma without direct cytotoxicity. Inhibition of NF-AT and NF-kappaB activation suggested phospholipase Cgamma (PLCgamma)-mediated Ca2+ mobilization and protein kinase C activation were blocked by (S)-armepavine. Phosphorylation of PLCgamma is regulated by lymphocyte-specific kinase (Lck), ZAP-70, and IL-2-inducible T cell kinase (Itk). We found (S)-armepavine inhibited PHA-induced phosphorylation of Itk and PLCgamma efficiently but did not influence Lck or ZAP-70 phosphorylation. In addition, ZAP-70-mediated pathways, such as the association of linker for activation of T cells with PLCgamma and activation of ERK, were also intact in the presence of (S)-armepavine. Finally, reduction of phosphoinositide 3,4,5 trisphosphate formation and Akt phosphorylation suggested that (S)-armepavine inhibited Itk, and PLCgamma phosphorylation might be a result of the influence of PI-3K activation. Addition of exogenous IL-2 or PMA/A23187 rescued PBMC proliferation in the presence of (S)-armepavine. Therefore, we concluded that (S) armepavine inhibited PHA-induced cell proliferation and cytokine production in a major way by blocking membrane-proximal effectors such as Itk and PLCgamma in a PI-3K-dependent manner. PMID- 17284685 TI - New ultrasound "elasticity" technique may reduce need for breast biopsies. PMID- 17284686 TI - Researchers explore rare lung disorder. PMID- 17284692 TI - MRI findings and cerebral palsy. PMID- 17284687 TI - New blood cancer therapies under study. PMID- 17284693 TI - MRI findings and cerebral palsy. PMID- 17284694 TI - MRI findings and cerebral palsy. PMID- 17284695 TI - Opiates and acute abdominal pain. PMID- 17284696 TI - Association between unreported outcomes and effect size estimates in Cochrane meta-analyses. PMID- 17284697 TI - Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. AB - CONTEXT: Acute safety concerns have been raised recently regarding certain hemorrhage-sparing medications commonly used in cardiac surgery. However, no comprehensive data exist regarding their associations with long-term mortality. OBJECTIVE: To contrast long-term all-cause mortality in patients undergoing coronary artery bypass graft (CABG) surgery according to use of 2 lysine analog antifibrinolytics (aminocaproic acid and tranexamic acid), the serine protease inhibitor aprotinin, or no antibleeding agent. DESIGN, SETTING, AND PARTICIPANTS: Observational study of mortality conducted between November 11, 1996, and December 7, 2006. Following index hospitalization (4374 patients; 69 medical centers), survival was prospectively assessed at 6 weeks, 6 months, and annually for 5 years after CABG surgery among 3876 patients enrolled in a 62-center international cohort study. The associations of survival with hemorrhage-sparing medications were compared using multivariable analyses including propensity adjustments. MAIN OUTCOME MEASURE: Death (all-cause) over 5 years. RESULTS: Aprotinin treatment (223 deaths among 1072 patients [20.8% 5-year mortality]) was associated with significantly increased mortality compared with control (128 deaths among 1009 patients [12.7%]; covariate adjusted hazard ratio for death, 1.48; 95% confidence interval, 1.19-1.85), whereas neither aminocaproic acid (132 deaths among 834 patients [15.8%]; adjusted hazard ratio for death, 1.03; 95% confidence interval, 0.80-1.33) nor tranexamic acid (65 deaths among 442 patients [14.7%]; adjusted hazard ratio for death, 1.07; 95% confidence interval, 0.80 1.45) was associated with increased mortality. In multivariable logistic regression, either with propensity adjustment or without, aprotinin was independently predictive of 5-year mortality (adjusted odds ratio with propensity adjustment, 1.48; 95% confidence interval, 1.13-1.93; P = .005) among patients with diverse risk profiles, as well as among those surviving their index hospitalization. Neither aminocaproic nor tranexamic acid was associated with increased risk of death. CONCLUSIONS: These findings indicate that in addition to the previously reported acute renal and vascular safety concerns, aprotinin use is associated with an increased risk of long-term mortality following CABG surgery. Use of aprotinin among patients undergoing CABG surgery does not appear prudent because safer and less expensive alternatives (ie, aminocaproic acid and tranexamic acid) are available. PMID- 17284698 TI - Economic return of clinical trials performed under the pediatric exclusivity program. AB - CONTEXT: In 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a "windfall" to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007. OBJECTIVE: To quantify the economic return to industry for completing pediatric exclusivity trials. DESIGN AND SETTING: A cohort study of programs conducted for pediatric exclusivity. Nine drugs that were granted pediatric exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return (cash inflows minus outflows) and net return-to-costs ratio (net economic return divided by cash outflows) for each product were then calculated. MAIN OUTCOME MEASURES: Net economic return and net return-to-cost ratio. RESULTS: The indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of exclusivity varied substantially among products (net economic return ranged from -$8.9 million to $507.9 million and net return-to-cost ratio ranged from -0.68 to 73.63). CONCLUSIONS: The economic return for pediatric exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric exclusivity can generate lucrative returns or produce more modest returns on investment. PMID- 17284699 TI - Association of genetic variations with nonfatal venous thrombosis in postmenopausal women. AB - CONTEXT: Although the roles of clotting proteins and enzymes that activate or inhibit fibrin production and lysis are well characterized, the underlying contribution of genetic variation in these constituents to risk of venous thrombosis (VT) has not been fully investigated. OBJECTIVE: To describe the association of common genetic variation in 24 coagulation, anticoagulation, fibrinolysis, and antifibrinolysis candidate genes with risk of incident nonfatal VT in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Population-based case-control study conducted in a large integrated health care system in Washington State. Participants were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first VT event between January 1995 and December 2002 (n = 349) and 1680 controls matched on age, hypertension status, and calendar year (n = 1680). MAIN OUTCOME MEASURE: Risk of venous thrombosis associated with global variation within a gene as measured by common haplotypes and with individual haplotypes and single nucleotide polymorphisms (SNPs). Significance of the associations was assessed by a .20 threshold of the false discovery rate q value, which accounts for multiple testing. RESULTS: Only the tissue factor pathway inhibitor gene demonstrated global association with risk (q = .13). Five significant SNP associations were identified across 3 of the candidate genes (factors V, XI, and protein C) in SNP analyses. Two associations have been previously reported. Another 22 variants across 15 genes had P values less than .05 but q values between .20 and .35. Five of these confirm previously reported associations (fibrinogen genes and protein C), 2 were inconsistent with earlier reports (thrombomodulin and plasminogen activator inhibitor 1), and 15 were new discoveries. CONCLUSIONS: After accounting for multiple testing, 5 SNPs associated with VT risk were identified, 3 of which have not been previously reported. Replication of these novel associations in other populations is necessary to corroborate these findings and identify which genetic factors may influence VT risk in postmenopausal women. PMID- 17284700 TI - Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. AB - CONTEXT: Statins reduce low-density lipoprotein cholesterol (LDL-C) levels and slow progression of coronary atherosclerosis. However, no data exist describing the relationship between statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and disease progression. OBJECTIVE: To investigate the relationship between changes in LDL-C and HDL-C levels and atheroma burden. DESIGN, SETTING, AND PATIENTS: Post-hoc analysis combining raw data from 4 prospective randomized trials (performed in the United States, North America, Europe, and Australia between 1999 and 2005), in which 1455 patients with angiographic coronary disease underwent serial intravascular ultrasonography while receiving statin treatment for 18 months or for 24 months. Ultrasound analysis was performed in the same core laboratory for all of the studies. MAIN OUTCOME MEASURE: Relationship between changes in lipoprotein levels and coronary artery atheroma volume. RESULTS: During statin therapy, mean (SD) LDL-C levels were reduced from 124.0 (38.3) mg/dL (3.2 [0.99] mmol/L) to 87.5 (28.8) mg/dL (2.3 [0.75] mmol/L) (a 23.5% decrease; P<.001), and HDL-C levels increased from 42.5 (11.0) mg/dL (1.1 [0.28] mmol/L) to 45.1 (11.4) mg/dL (1.2 [0.29] mmol/L) (a 7.5% increase; P<.001). The ratio of LDL-C to HDL-C was reduced from a mean (SD) of 3.0 (1.1) to 2.1 (0.9) (a 26.7% decrease; P<.001). These changes were accompanied by a mean (SD) increase in percent atheroma volume from 39.7% (9.8%) to 40.1% (9.7%) (a 0.5% [3.9%] increase; P = .001) and a mean (SD) decrease in total atheroma volume of 2.4 (23.6) mm3 (P<.001). In univariate analysis, mean levels and treatment-mediated changes in LDL-C, total cholesterol, non-HDL cholesterol, apolipoprotein B, and ratio of apolipoprotein B to apolipoprotein A I were significantly correlated with the rate of atherosclerotic progression, whereas treatment-mediated changes in HDL-C were inversely correlated with atheroma progression. In multivariate analysis, mean levels of LDL-C (beta coefficient, 0.11 [95% confidence interval, 0.07-0.15]) and increases in HDL-C (beta coefficient, -0.26 [95% confidence interval, -0.41 to -0.10]) remained independent predictors of atheroma regression. Substantial atheroma regression (> or =5% reduction in atheroma volume) was observed in patients with levels of LDL C less than the mean (87.5 mg/dL) during treatment and percentage increases of HDL-C greater than the mean (7.5%; P<.001). No significant differences were found with regard to clinical events. CONCLUSIONS: Statin therapy is associated with regression of coronary atherosclerosis when LDL-C is substantially reduced and HDL-C is increased by more than 7.5%. These findings suggest that statin benefits are derived from both reductions in atherogenic lipoprotein levels and increases in HDL-C, although it remains to be determined whether the atherosclerotic regression associated with these changes in lipid levels will translate to meaningful reductions in clinical events and improved clinical outcomes. PMID- 17284701 TI - A 27-year-old woman with a diagnosis of polycystic ovary syndrome. AB - Ms R, a 27-year-old woman with polycystic ovary syndrome (PCOS) diagnosed after irregular menses, hirsutism, and polycystic ovaries, is concerned about weight gain despite regular exercise and watching her diet. Prescribed oral contraceptives to regulate her menses and help reduce her androgen levels, she wants to know the alternatives for treatment of PCOS. The varying definitions of PCOS and its heterogeneity confound the interpretation of studies on PCOS. Specific diagnostic criteria have been established based on expert opinion but have not been validated. Several commonly performed laboratory tests are generally unhelpful and the pathophysiology is poorly understood. Treatment options for Ms R, including those that may affect her weight gain, are reviewed and implications for future fertility are discussed. PMID- 17284702 TI - Measuring progress toward achieving hemoglobin A1c goals in diabetes care: pass/fail or partial credit. PMID- 17284703 TI - Potential health and economic consequences of misplaced priorities. PMID- 17284704 TI - Aprotinin--are there lessons learned? PMID- 17284705 TI - Interpreting results of large-scale genetic association studies: separating gold from fool's gold. PMID- 17284706 TI - JAMA patient page. Polycystic ovary syndrome. PMID- 17284707 TI - Granulocyte colony-stimulating factor: key (f)actor or innocent bystander in the development of secondary myeloid malignancy? PMID- 17284708 TI - An affair of the heart. PMID- 17284710 TI - Lung cancer screening debate continues despite international CT study results. PMID- 17284709 TI - SNPs not living up to promise; experts suggest new approach to disease ID. PMID- 17284711 TI - Blood, spit, and breath: scientists search for noninvasive tests for lung cancer. PMID- 17284713 TI - Stat bite: Major causes of death in the U.S. PMID- 17284712 TI - With targeted drugs, chronic myelogenous leukemia therapy may follow HIV's model. PMID- 17284714 TI - Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. AB - BACKGROUND: Recently, increasing numbers of women receiving adjuvant chemotherapy for breast cancer have also received granulocyte colony-stimulating factors (G CSFs) or granulocyte-macrophage colony-stimulating factors (GM-CSFs). Although these growth factors support chemotherapy, their long-term safety has not been evaluated. We studied the association between G-CSF use and incidence of leukemia in a population-based sample of breast cancer patients. METHODS: Among women aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stages I-III breast cancer from January 1, 1991, to December 31, 1999, we identified those who received G-CSF or GM-CSF concurrently with chemotherapy. We used Cox proportional hazards models to estimate hazard ratios for the association of treatment with G-CSF or GM-CSF and subsequent (through December 31, 2003) diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). All statistical tests were two-sided. RESULTS: Of 5510 women treated with chemotherapy, 906 (16%) received G-CSF or GM-CSF therapy, and 64 (1.16%) were subsequently diagnosed with either MDS or AML before a cancer recurrence. Use of G-CSF and GM-CSF was associated with more recent diagnosis, younger age, urban residence, fewer comorbidities, receipt of radiation therapy, positive lymph nodes, and cyclophosphamide treatment. Of the 906 patients who were treated with G-CSF, 16 (1.77%) developed AML or MDS; of the 4604 patients not treated with G-CSF, 48 (1.04%) developed AML or MDS. The hazard rate ratio for AML or MDS among those treated with G-CSF or GM-CSF compared with those who were not was 2.14 (95% confidence interval [CI] = 1.12 to 4.08). AML or MDS developed within 48 months of breast cancer diagnosis in 1.8% of patients who received G-CSF or GM-CSF but only in 0.7% of patients who did not (hazard ratio = 2.59, 95% CI = 1.30 to 5.15). CONCLUSIONS: The use of G-CSF was associated with a doubling in the risk of subsequent AML or MDS among the population that we studied, although the absolute risk remained low. Even if this association is confirmed, the benefits of G-CSF may still outweigh the risks. Meanwhile, however, G-CSF use should not be assumed to be risk free. PMID- 17284715 TI - Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. AB - BACKGROUND: Myocardial infarction is a major cause of excess long-term mortality in survivors of Hodgkin disease, but limited information exists on the effects of specific chemotherapy regimens used to treat these patients on their risk of death from myocardial infarction. METHODS: We followed a cohort of 7033 Hodgkin disease patients who were treated in Britain from November 1, 1967, through September 30, 2000, and compared their risk of myocardial infarction mortality with that in the general population of England and Wales. All statistical tests were two-sided. RESULTS: A total of 166 deaths from myocardial infarction occurred in the cohort, statistically significantly more than expected (standardized mortality ratio [SMR] = 2.5, 95% confidence interval [CI] = 2.1 to 2.9), with an absolute excess risk of 125.8 per 100,000 person-years. Standardized mortality ratios decreased sharply with older age at first treatment, but absolute excess risks of death from myocardial infarction increased with older age up to age 65 years at first treatment. The statistically significantly increased risk of myocardial infarction mortality persisted through to 25 years after first treatment. Risks were increased statistically significantly and independently for patients who had been treated with supradiaphragmatic radiotherapy, anthracyclines, or vincristine. Risk was particularly high for patients treated with the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (SMR = 9.5, 95% CI = 3.5 to 20.6). Risk at 20 or more years after first treatment was particularly great for patients who had received supradiaphragmatic radiotherapy and vincristine without anthracyclines (SMR = 14.8, 95% CI = 4.8 to 34.5). CONCLUSIONS: The risk of death from myocardial infarction after treatment for Hodgkin disease remains high for at least 25 years. The increased risks are related to supradiaphragmatic radiotherapy but may also be related to anthracycline and vincristine treatment. PMID- 17284716 TI - Second cancer incidence and cause-specific mortality among 3104 patients with hairy cell leukemia: a population-based study. AB - BACKGROUND: The introduction of new treatments for hairy cell leukemia has resulted in improved patient survival but also engendered increasing concern about the possibility of excess second cancers. The available evidence is conflicting, with most risk estimates based on sparse numbers. To our knowledge, no study has evaluated cause-specific mortality in patients with hairy cell leukemia. METHODS: We quantified second cancer incidence and cause-specific mortality among 3104 two-month survivors of hairy cell leukemia who were reported to 16 population-based registries in the Surveillance, Epidemiology and End Results (SEER) Program between 1973 and 2002. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were used to quantify the risk of second cancers and causes of death, respectively. The cumulative probability of a second cancer among survivors of hairy cell leukemia was calculated using a competing risk model. All statistical tests were two-sided. RESULTS: Mean follow up of hairy cell leukemia survivors was 6.5 years (range, 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.24, 95% confidence interval [CI] = 1.11 to 1.37) compared with the general population. Survivors had statistically significantly higher risks of Hodgkin lymphoma (SIR = 6.61, 95% CI = 2.13 to 15.42), non-Hodgkin lymphoma (SIR = 5.03, 95% CI = 3.77 to 6.58), and thyroid cancer (SIR = 3.56, 95% CI = 1.30 to 7.74) and a lower risk of lung cancer (SIR = 0.63, 95% CI = 0.42 to 0.90). The cumulative probability of all second cancers was estimated to be 31.9% (95% CI = 26.2 to 37.6) 25 years after hairy cell leukemia diagnosis. Among 10,000 hairy cell leukemia patients, a total excess of about 34 cancers, including 21 non-Hodgkin lymphomas, 2 Hodgkin lymphomas, and 7 solid tumors (including 2 thyroid cancers), might be observed per year. Deaths due to solid tumors were not elevated compared with the general population (SMR = 0.9), and there were statistically significant deficits in mortality due to both cardiovascular (SMR = 0.67, 95% CI = 0.56 to 0.80) and cerebrovascular (SMR = 0.61, 95% CI = 0.38 to 0.93) disease. CONCLUSIONS: Patients with hairy cell leukemia are at increased risk of Hodgkin lymphoma, non Hodgkin lymphoma, and thyroid cancer. The decrease in lung cancer incidence and smoking-associated vascular mortality may reflect an inverse association of tobacco use with hairy cell leukemia. Future studies should address the roles of immunologic impairment inherent to hairy cell leukemia, treatment modalities, and other factors as codeterminants of morbidity and mortality in hairy cell leukemia survivors. PMID- 17284718 TI - Quality of reporting of cancer prognostic marker studies: association with reported prognostic effect. AB - BACKGROUND: Issues of reported study quality have not been addressed empirically with large-scale data in the cancer prognostic literature. METHODS: Eight quality measures pertaining to study design and assay methods (i.e., blinding, prospective versus retrospective design, power calculations, outcomes' definitions, time of enrollment, reporting of variables, assay description, and assay reference) were evaluated in cancer prognostic marker studies included in meta-analyses identified in Medline and EMBASE. To be eligible, meta-analyses had to include at least six studies and to examine binary outcomes. We estimated the ratios of relative risks, which compared the overall prognostic effects (summary relative risks) between poor-quality and good-quality studies for each quality item. Between-study heterogeneity was tested with the Q statistic (statistically significant at P<.10). All statistical tests were two-sided. RESULTS: We identified 20 meta-analyses that included 331 cancer prognostic marker studies published between 1987 and 2005. Only three (0.9%) of the 331 studies presented power calculations, 129 (39.0%) studies stated that analyses were blinded, and 73 (21.5%) stated that they were prospective. Time of enrollment was defined in 232 (70.0%), 234 (70.7%) gave lists of candidate variables, and 254 (76.7%) defined outcomes. The assay used was described in 317 (95.8%), but only 177 (53.5%) provided the assay reference. Estimates of prognostic effects from poor-quality studies varied considerably and could be larger or smaller than summary estimates derived from meta-analyses. Summary ratios of relative risks of poor- versus good quality studies for the seven quality measures ranged from 0.95 to but 1.26, but none was statistically significantly. There was statistically significant heterogeneity (P<.10) between the ratios of relative risk estimates across meta analyses for blinding, defining endpoints, and stating variables and assay references. CONCLUSIONS: Among cancer prognostic marker studies, reporting quality of design and assay information often appears suboptimal, indicating that this literature may be largely unreliable. Given the potential clinical importance of prognostic marker information, improved design and reporting of these studies are warranted. PMID- 17284717 TI - Effect of fibroblast growth factor 2 on stromal cell-derived factor 1 production by bone marrow stromal cells and hematopoiesis. AB - BACKGROUND: Reduction of intramedullary hematopoiesis and the development of myelofibrosis and splenic hematopoiesis are frequent complications of clonal myeloid disorders that cause severe morbidity and death and present a therapeutic challenge. However, the pathogenesis of these complications is still unknown. We evaluated the effect of fibroblast growth factor 2 (FGF-2), the level of which is elevated in patients with clonal myeloid disorders, on bone marrow stromal cell expression of stromal cell-derived factor 1 (SDF-1), a chemokine that is essential for normal hematopoiesis. METHODS: Reverse transcription-polymerase chain reaction analysis, immunoblot analysis, and enzyme-linked immunosorbent assays were used to examine effects of human recombinant FGF-2 exposure on SDF-1 expression in mouse stromal MS-5 and S-17 cells. Cocultures of human CD34 positive peripheral blood stem cells or mouse pre-B DW34 cells with mouse stromal cells were used to characterize the functional relevance of the effects of FGF-2 on SDF-1 expression. The in vivo hematologic effects of FGF-2 were determined by systemic administration to mice (n = 10). All statistical tests were two-sided. RESULTS: FGF-2 reduced constitutive SDF-1 mRNA expression and secretion in stromal cells (SDF-1 levels in supernatants: MS-5 cells cultured for 3 days in medium only versus in medium with FGF-2, 95.4 ng/mL versus 22.2 ng/mL, difference = 73.2 ng/mL, 95% confidence interval [CI] = 60.52 to 85.87 ng/mL; P = .002, two sided Student's t test; S-17 cultured in medium only versus in medium with FGF-2, 203.53 ng/mL versus 32.36 ng/mL, difference = 171.17 ng/mL, 95% CI = 161.8 to 180.6 ng/mL; P<.001). These effects of FGF-2 were reversible. FGF-2 compromised stromal cell support of the growth and survival of pre-B DW34 and myeloid lineage cells, and these effects were reversed in part by exogenous recombinant SDF 1alpha (rSDF-1alpha) (DW34 pre-B cells recovery on S-17 stromal cells, expressed as a percentage of DW34 cells recovered from medium only: with FGF-2 versus without FGF-2, 27.6% versus 100%, difference = 72.4%, 95% CI = 45.34% to 99.51%, P = .008; with FGF-2 plus rSDF1 versus with FGF-2 only, 60.3% versus 27.6%, difference = 32.7%, 95% CI = 9.35% to 56.08%, P = .034; fold increase in number of myeloid lineage cells after culture on S-17 stromal cells: with FGF-2 versus without FGF-2, 0.25-fold versus 3.8-fold, difference = 3.55-fold, 95% CI = 2.66- to 4.44-fold, P<.001; recovery of myeloid cells on S-17 stromal cells, expressed as a percentage of myeloid cells recovered from medium only: FGF-2 plus rSDF 1alpha versus FGF-2 only, 76.5% versus 32.4%, difference = 44.1%, 95% CI = 32.58% to 55.68%, P<.001). Administration of FGF-2 to mice reversibly reduced bone marrow levels of SDF-1 and cellularity and induced immature myeloid cell mobilization, extramedullary hematopoiesis, and splenomegaly. CONCLUSIONS: Systemic administration of FGF-2 in mice disrupts normal bone marrow hematopoiesis in part through reduced expression of SDF-1. Thus, endogenous FGF-2 may represent a potential therapeutic target in clonal myeloid disorders characterized by bone marrow failure. PMID- 17284720 TI - Re: Tissue banks trigger worry about ownership issues. PMID- 17284719 TI - Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors. AB - BACKGROUND: Colorectal tumors caused by failure of the DNA mismatch repair system commonly show microsatellite instability. Our goals were to compare the performance of two panels of markers (a panel previously recommended by the National Cancer Institute [NCI] and a pentaplex of mononucleotide repeats) and to devise the simplest diagnostic strategy for identification of patients with colorectal cancer characterized by defects in mismatch repair. METHODS: We recruited 1058 patients who were newly diagnosed with colorectal cancer. DNA from fresh-frozen and paraffin-embedded tumors was tested for microsatellite instability, using the NCI-recommended panel of microsatellite markers and the pentaplex panel of mononucleotide repeats, respectively, as templates for polymerase chain reactions (PCRs). Microsatellite instability in fresh-frozen tumors was also assessed using the pentaplex panel of mononucleotides in a crossover analysis. The expression of mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) in the tumors was determined immunohistochemically. The sensitivity and specificity with which the marker panels identified tumors with deficiencies in the expression of mismatch repair proteins were calculated. All statistical tests were two-sided. RESULTS: The sensitivity and positive predictive value of the NCI panel were 76.5% (95% confidence interval [CI] = 61% to 92%) and 65.0% (95% CI = 49% to 81%), respectively; corresponding values for the mononucleotide pentaplex panel were 95.8% (95% CI = 89% to 103%) and 88.5% (95% CI = 79% to 98%), respectively. A panel consisting of the mononucleotide repeat markers BAT26 and NR24 alone had the same predictive value as the pentaplex panel of mononucleotide repeats. CONCLUSIONS: The pentaplex panel of mononucleotide repeats performs better than the NCI panel for the detection of mismatch repair-deficient tumors. Simultaneous assessment of the instability of BAT26 and NR24 is as effective as use of the pentaplex panel for diagnosing mismatch repair deficiency. PMID- 17284721 TI - Preeclampsia, pregnancy-related hypertension, and breast cancer risk. AB - Pregnancy conditions accompanied by high blood pressure, such as preeclampsia and pregnancy-related hypertension, have been associated with a lower risk of breast cancer in several epidemiologic studies. It is unknown whether length of gestation or multiple occurrence of these conditions alters the association with breast cancer. It is also unknown whether the inverse association between preeclampsia and breast cancer risk is modified by menopausal status at breast cancer diagnosis. Using data from a large, population-based case-control study of breast cancer conducted on Long Island, New York, during 1996-1997, the authors examined these questions among ever-parous women (1,310 cases and 1,385 controls) using multivariate logistic models. Preeclampsia was inversely associated with breast cancer (odds ratio = 0.7, 95% confidence interval: 0.5, 1.0); this association was even stronger among women who had multiple occurrences of preeclampsia (odds ratio = 0.3, 95% confidence interval: 0.1, 0.9). The risk reduction was more pronounced among postmenopausal women. Gestation length did not substantially alter the relation between preeclampsia and breast cancer risk. Pregnancy-related hypertension was also inversely associated with breast cancer risk, but the relations were not statistically significant after adjustment for preeclampsia. These data suggest that pregnancy conditions related to hypertension, particularly preeclampsia, play a role in reducing breast cancer risk. Possible biologic mechanisms underpinning these associations should be further explored. PMID- 17284722 TI - A prospective study of plasma ferritin level and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. AB - The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development. PMID- 17284724 TI - Neuronal polarity and the kinesin superfamily proteins. AB - Neurons are highly polarized cells, typically with a long axon and relatively short dendrites. A wealth of recent data has identified a number of signaling molecules that are involved in neuronal polarization. Kinesin superfamily proteins (KIFs) contribute to the establishment and maintenance of neuronal polarity by selectively transporting various proteins and vesicles to either the axon or dendrites. Now evidence is emerging that KIFs also play an important role in axonal formation, the initial event of neuronal polarization. In particular, KIF13B transports phosphatidylinositol (3,4,5)-trisphosphate, which, based on current hypotheses, is one of the most upstream molecules in the intracellular signaling cascades involved in axonal formation. PMID- 17284723 TI - A prospective study of childhood and adult socioeconomic status and incidence of type 2 diabetes in women. AB - The influence of childhood socioeconomic status (SES) on incidence of type 2 diabetes mellitus has not previously been studied. The authors prospectively examined the association of childhood SES (father's occupation) with incidence of diabetes in 100,330 US women who were followed from 1980 to 2002. In 55,115 of those women, 10-year follow-up data (1992-2002) were also available on adult SES (spouse's education). In all, 6,916 new cases of type 2 diabetes were documented. Compared with women from white-collar occupational backgrounds, the multivariate adjusted risks of diabetes were 1.08 (95% confidence interval (CI): 0.95, 1.23) among women whose fathers were laborers and 1.10 (95% CI: 1.03, 1.16) among women whose fathers were blue-collar or lower white-collar workers. Lower adult SES was associated with risk of diabetes independently of childhood SES. Compared with women whose spouses had graduate degrees, women whose spouses were high school graduates had a 1.16 times higher risk of incident diabetes (95% CI: 1.04, 1.29), while women whose spouses had college degrees were at 1.14 times the risk (95% CI: 1.01, 1.29). Compared with women with stable high SES from childhood to adulthood, women with declining SES had a 1.18 times higher risk of incident diabetes (95% CI: 1.06, 1.32). Higher body mass index among women with lower SES accounted for much of these rather modest associations between childhood and adult SES and risk of diabetes. PMID- 17284725 TI - Homocysteine, B vitamins, and the risk of dementia. PMID- 17284726 TI - Postprandial lipoprotein metabolism--pivot or puzzle? PMID- 17284727 TI - Micronutrients in HIV-positive persons receiving highly active antiretroviral therapy. AB - In HIV-infected persons, low serum concentrations of vitamins and minerals, termed micronutrients, are associated with an increased risk of HIV disease progression and mortality. Micronutrient supplements can delay HIV disease progression and reduce mortality in HIV-positive persons not receiving highly active antiretroviral therapy (HAART). With the transition to more universal access to HAART, a better understanding of micronutrient deficiencies and the role of micronutrient supplements in HIV-positive persons receiving HAART has become a priority. The provision of simple, inexpensive micronutrient supplements as an adjunct to HAART may have several cellular and clinical benefits, such as a reduction in mitochondrial toxicity and oxidative stress and an improvement in immune reconstitution. We reviewed observational and trial evidence on micronutrients in HIV-positive persons receiving HAART to summarize the current literature and suggest future research priorities. A small number of observational studies have suggested that some, but not all, micronutrients may become replete after HAART initiation, and few intervention studies have found that certain micronutrients may be a beneficial adjunct to HAART. However, most of these studies had some major limitations, including a small sample size, a short duration of follow-up, a lack of adjustment for inflammatory markers, and an inadequate assessment of HIV-related outcomes. Therefore, few data are available to determine whether HAART ameliorates micronutrient deficiencies or to recommend or refute the benefit of providing micronutrient supplements to HIV positive persons receiving HAART. Because micronutrient supplementation may cause harm, randomized placebo-controlled trials are needed. Future research should determine whether HAART initiation restores micronutrient concentrations, independent of inflammatory markers, and whether micronutrient supplements affect HIV-related outcomes in HIV-positive persons receiving HAART. PMID- 17284728 TI - Why do obese patients not lose more weight when treated with low-calorie diets? A mechanistic perspective. AB - Maximal weight loss observed in low-calorie diet (LCD) studies tends to be small, and the mechanisms leading to this low treatment efficacy have not been clarified. Less-than-expected weight loss with LCDs can arise from an increase in fractional energy absorption (FEA), adaptations in energy expenditure, or incomplete patient diet adherence. We systematically reviewed studies of FEA and total energy expenditure (TEE) in obese patients undergoing weight loss with LCDs and in patients with reduced obesity (RO), respectively. This information was used to support an energy balance model that was then applied to examine patient adherence to prescribed LCD treatment programs. In the limited available literature, FEA was unchanged from baseline in short-term (<12 wk) treatment studies with LCDs; no long-term (>or=26 wk) studies were found. Review of doubly labeled water and respiratory chamber studies identified 10 reports of TEE in RO patients (n = 150) with long-term weight loss. These patients, who were weight stable, had a TEE almost identical to measured or predicted values in never-obese subjects (weighted mean difference: 1.3%; range: -1.7-8.5%). Modeling of energy balance, as supported by reviewed FEA and TEE studies, suggests that obese subjects participating in LCD programs have a weight loss less than half of that predicted. The small maximal weight loss observed with LCD treatments thus is likely not due to gastrointestinal adaptations but may be attributed, by deduction, to difficulties with patient adherence or, to a lesser degree, to metabolic adaptations induced by negative energy balance that are not captured by the current models. PMID- 17284729 TI - Television watching increases motivated responding for food and energy intake in children. AB - BACKGROUND: Sedentary activities, such as watching television, may disrupt habituation to food cues, thereby increasing motivation to eat and energy intake. OBJECTIVE: These experiments were designed to examine the effect of television watching on habituation of ingestive behavior in children. DESIGN: In experiment 1, all children worked for access to cheeseburgers in trials 1-7 (habituating stimulus). In trials 8-10, children in the control group continued to work for cheeseburgers without any dishabituating stimuli, whereas children in the other groups received either a novel food (French fries) or television as dishabituating stimuli. Responding for food and amount of food eaten were measured. In experiment 2, all children had access to 1000 kcal of a preferred snack food. One group watched a continuous television show, and the control groups either watched no television or watched a repeated segment of a television show, which controls for the television stimulus but requires reduced allocation of attention. RESULTS: In experiment 1, both the novel food and the television watching groups reinstated responding for food (P = 0.009) and increased the amount of energy earned (P = 0.018) above the level of the control subjects. In experiment 2, the continuous television group spent more time eating (P < 0.0001) and consumed more energy than the no television and the repeated segment groups (P = 0.007). CONCLUSION: These experiments show that television watching can dishabituate eating or disrupt the development of habituation, which may provide a mechanism for increased energy intake associated with watching television. PMID- 17284731 TI - Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein B containing lipoproteins and vascular reactivity in type 2 diabetes. AB - BACKGROUND: Plasma lipoproteins may be classified by their apolipoprotein composition. The lipoprotein subclass containing apolipoproteins B and C (LpB:C) is considered the most atherogenic. OBJECTIVE: We evaluated the acute effects of individual fatty acids on apolipoprotein B (apo B)-containing lipoproteins in adults with type 2 diabetes (n = 15). DESIGN: We administered 3 meals in a randomized, double-blind, crossover design. Treatments contained skim milk and 50 g fat from high-oleic acid safflower and canola oils (monounsaturated fatty acid; MUFA), MUFA + 3.5 g alpha-linolenic acid (ALA; MUFA + ALA) from high-ALA canola oil, or MUFA + 4.0 g both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; MUFA + EPA/DHA) from sardine oil. Apo B, LpB, LpB:C, LpB:E + LpB:C:E, and LpA-II:B:C:D:E were measured at baseline and 2 and 4 h after the meal. Flow mediated dilation was measured at baseline and 4 h after the meal. RESULTS: The treatments significantly increased apo B and LpB postprandially (P < 0.03 for both), but the magnitude of the changes did not differ significantly between the treatments. The postprandial change in LpB:C was 23% lower after MUFA + EPA/DHA than after MUFA (treatment x time interaction, P < 0.0001). MUFA + ALA attenuated the increase in LpA-II:B:C:D:E in those with high triacylglycerols (>/=1.69 mmol/L) but was the only treatment to significantly increase this particle in those with low triacylglycerols (treatment x group interaction, P < 0.0001). Examination of change scores did not reveal the source of the interaction of treatment and time (P < 0.007) for LpB:E + LpB:C:E. Furthermore, the subjects with the largest increases in LpB:C exhibited the largest impairment in endothelial function. CONCLUSIONS: The results suggest that unsaturated fatty acids differentially affect concentrations of apo B-containing lipoprotein subclasses. A rise in LpB:C adversely affects endothelial function. Meals containing MUFA + EPA/DHA attenuated the postprandial rise in LpB:C and the impairment of endothelial function. PMID- 17284730 TI - Approximation of total visceral adipose tissue with a single magnetic resonance image. AB - BACKGROUND: A single axial image measured between the 4th and 5th lumbar vertebrae (L4-L5) is most frequently chosen to approximate total abdominal visceral adipose tissue (VAT) volume, but growing evidence suggests that this measurement site is not ideal. OBJECTIVE: The objective was to determine the single magnetic resonance (MR) image that best approximates the total VAT volume in a biracial sample of healthy subjects. DESIGN: We used contiguous abdominal MR images to measure VAT area and summed them to determine total VAT volume. The sample included 820 healthy men and women (n = 692 whites, 128 blacks) aged 18-88 y. RESULTS: A range of MR images had equally high correlations with total VAT in each race and sex group. The image 6 cm above L4-L5 (L4-L5 + 6) was within the best equivalent range for all race and sex groups. The L4-L5 + 6 image crossed the L3 vertebra in 85% of subjects and crossed the L2-L3 intervertebral space or the L2 vertebra for 15% of subjects. Linear regression models indicated that the L4-L5 + 6 image explained 97% of the variance in total abdominal VAT volume, and additional covariates did not increase the R(2) value significantly. The L4-L5 image explained 83% of the variance in VAT volume, and the covariates accounted for an additional 7% of the variance. Rank-order values for VAT can change if total VAT volume is approximated by a single image area. Whereas 25% of subjects changed rank by >or=10% with the L4-L5 image, only 3% changed rank to that degree with the L4-L5 + 6 image. CONCLUSIONS: A single MR image located approximately at the L3 vertebra can accurately estimate total VAT volume in blacks and whites of both sexes. PMID- 17284732 TI - Reduced physical activity increases intermuscular adipose tissue in healthy young adults. AB - BACKGROUND: Recent findings suggest that higher levels of intermuscular adipose tissue (IMAT) are associated with glucose dysregulation, lower levels of muscle strength, and a heightened risk of disability. Although several studies have described adaptations in muscle after reduced physical activity, the change in IMAT in healthy young adults is unknown. OBJECTIVE: The objective was to determine whether reduced lower limb activity alters IMAT in healthy young adults and to assess whether this change affects muscle strength loss. DESIGN: The subjects (6 men and 12 women aged 19-28 y) underwent a 4-wk control period, which was followed by 4 wk of unilateral lower limb suspension. Volumes of whole muscle, subcutaneous adipose tissue, and IMAT were assessed by using magnetic resonance imaging in the thigh and calf. Muscle strength was assessed during maximal voluntary isometric contractions. RESULTS: No changes were observed in the control period. Reduced physical activity decreased thigh and calf muscle volumes by 7.4% and 7.9% (P < 0.001), respectively; no significant change in subcutaneous adipose tissue was observed. Additionally, IMAT increased in both regions; the increase was larger in the calf (20%) than in the thigh (14.5%) (P or=65 y with higher caffeinated beverage intake exhibited lower relative risk of CVD and heart disease mortality than did participants with lower caffeinated beverage intake. It was a dose-response protective effect: the relative risk (95% CI) for heart disease mortality was 1.00 (referent), 0.77 (0.54, 1.10), 0.68 (0.49, 0.94), and 0.47 (0.32, 0.69) for <0.5, 0.5-2, 2-4, and >or=4 servings/d, respectively (P for trend = 0.003). A similar protective effect was found for caffeine intake in mg/d. The protective effective was found only in participants who were not severely hypertensive. No significant protective effect was found in participants aged <65 y or in cerebrovascular disease mortality for those aged >or=65 y. CONCLUSION: Habitual intake of caffeinated beverages provided protection against the risk of heart disease mortality among elderly participants in this prospective epidemiologic analysis. PMID- 17284735 TI - Serum visfatin concentrations are positively correlated with serum triacylglycerols and down-regulated by overfeeding in healthy young men. AB - BACKGROUND: Visfatin is an insulin-mimicking adipokine. Visfatin is elevated in obesity and type 2 diabetes. However, its role in glucose and lipid metabolism in healthy humans is unclear. OBJECTIVE: The objective was to investigate the correlations of visfatin with phenotypes of glucose, lipids, and body composition and the responses of visfatin to short-term overfeeding in healthy young men. DESIGN: Sixty-one healthy young men were recruited from the Newfoundland population. Serum visfatin, interleukin 6, glucose, insulin, total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol concentrations were measured with an autoanalyzer, and percentage body fat (%BF) and percentage trunk fat (%TF) were measured with dual-energy X-ray absorptiometry. Insulin resistance and beta cell function were assessed with the homeostasis model. All measurements were completed at baseline and after a 7-d overfeeding protocol exceeding the baseline requirement by 70%. Subjects were classified on the basis of %BF as lean (<21%), overweight (21-25.9%), or obese (>or=26%). RESULTS: Multiple regression analysis showed that triacylglycerols correlated with fasting serum visfatin (P < 0.001). Moreover, serum visfatin decreased 19% overall-23% in lean, 9% in overweight, and 18% in obese subjects (P < 0.0001)-after the overfeeding protocol. None of the variables measured, including interleukin 6, were associated with the reduction in visfatin. In contrast with the findings in mice, visfatin concentrations before and after overfeeding did not correlate with glucose, insulin, insulin resistance, beta cell function, %BF, or %TF. CONCLUSIONS: Visfatin is down-regulated by overfeeding. Under physiologic conditions, visfatin does not appear to control glucose metabolism but may play a regulatory role in lipid metabolism. PMID- 17284736 TI - Effects of birth cohort and age on body composition in a sample of community based elderly. AB - BACKGROUND: The effect of the recent obesity epidemic on body composition remains unknown. Furthermore, age-related changes in body composition are still unclear. OBJECTIVE: The objective was to simultaneously examine the effects of birth cohort and age on body composition. DESIGN: A total of 1786 well-functioning, community-based whites and blacks (52% women and 35% blacks) aged 70-79 y from the Health, Aging, and Body Composition Study underwent dual-energy X-ray absorptiometry annually from 1997 to 2003. RESULTS: At baseline, mean +/- SD percentage body fat, fat mass, and lean mass (bone-free) were 28 +/- 5%, 24 +/- 7 kg, and 56 +/- 7 kg, respectively, for men and 39 +/- 6%, 28 +/- 9 kg, and 40 +/- 6 kg for women. Mixed models were used to assess the effects of cohort and age related changes on body composition. Later cohorts in men had a greater percentage body fat (0.32% per birth year, P < 0.0001) than did earlier cohorts. This cohort effect was due to a greater increase in fat mass than in lean mass (0.45 kg and 0.17 kg/birth year, respectively). With increasing age, percentage body fat in men initially increased and then leveled off. This age-related change was due to an accelerated decrease in lean mass and an initial increase and a later decrease in fat mass. Similar but less extreme effects of cohort and age were observed in women. CONCLUSIONS: The combination of effects of both birth cohort and age leads to bigger body size and less lean mass in the elderly. PMID- 17284737 TI - Effect of different macronutrients in excess on gastric sensory and motor functions and appetite in normal-weight, overweight, and obese humans. AB - BACKGROUND: The effects of supplementation with different macronutrients on gastric sensory and motor functions are unclear. OBJECTIVE: We aimed to compare the effects of 2 wk of supplementation with different classes of macronutrients on gastric function, satiation, and appetite in healthy and overweight subjects. DESIGN: In a parallel-group, double-blind study, 52 (14 men, 38 women) healthy normal-weight, overweight, and obese participants [body mass index (BMI; in kg/m(2)): 19.4-47.0] aged 18-64 y were randomly assigned to consume different isocaloric diets (n = 13 per diet group) adjusted for BMI and activity level. The standard diet provided 20% of energy as protein, 30% as fat, and 50% as carbohydrate. The high-protein, high-fat, and high-carbohydrate diets contained 500 additional kcal in each nutrient class. On 3 separate days, we measured gastric emptying of solids, gastric volumes, postprandial symptoms, appetite, and food choice with validated methods. Age, sex, BMI, and baseline satiation were covariates in the analysis of covariance. RESULTS: Fat supplementation was associated with increased maximum tolerated volume (MTV) in subjects with a high baseline MTV (P < 0.05), irrespective of BMI. Gastric emptying and volumes, postprandial symptoms, total calories, and food choices at an ad libitum meal were not significantly different after each dietary preload. Fasting gastric volumes tended to be higher with the high-fat than with the high-carbohydrate or high-protein diets (P 30). CONCLUSION: Supplementation with 500 kcal fat in excess of required calories for 2 wk increased food tolerance in healthy normal-weight and obese subjects with a high baseline MTV without significantly changing gastric motor functions. PMID- 17284739 TI - High-glycemic-index carbohydrate meals shorten sleep onset. AB - BACKGROUND: Dietary carbohydrate intake has been shown to increase the plasma concentration of tryptophan, a precursor of serotonin and sleep-inducing agent. OBJECTIVE: To investigate the role of carbohydrate in sleep induction, we explored the effect of glycemic index (GI) and meal time on sleep in healthy volunteers. DESIGN: We compared the effect of high- and low-GI carbohydrate-based meals ingested 4 h before bedtime on sleep quality. We also evaluated the effect of the timing of high-GI meals (4 h compared with 1 h) on sleep quality. Twelve healthy men (aged 18-35 y) were administered standard, isocaloric (3212 kJ; 8% of energy as protein, 1.6% of energy as fat, and 90.4% of energy as carbohydrate) meals of either Mahatma (low GI = 50) or Jasmine (high GI = 109) rice 4 h before their usual bedtime. On another occasion, the high-GI meal was given 1 h before bedtime. The participants underwent a familiarization night followed by 3 test nights in random order 1 wk apart. RESULTS: A significant (P = 0.009) reduction in the mean (+/-SD) sleep onset latency (SOL) was observed with a high-GI (9.0 +/ 6.2 min) compared with a low-GI (17.5 +/- 6.2 min) meal consumed 4 h before bedtime. The high-GI meal given 4 h before bedtime showed a significantly shortened SOL compared with the same meal given 1 h before bedtime (9.0 +/- 6.2 min compared with 14.6 +/- 9.9 min; P = 0.01). No effects on other sleep variables were observed. CONCLUSIONS: We showed that a carbohydrate-based high-GI meal resulted in a significant shortening of SOL in healthy sleepers compared with a low-GI meal and was most effective when consumed 4 h before bedtime. The relevance of these findings to persons with sleep disturbance should be determined in future trials. PMID- 17284738 TI - BMI compared with 3-dimensional body shape: the UK National Sizing Survey. AB - BACKGROUND: Human body shape is a rich source of information about health and the risk of disease. Measuring anthropometry manually is time-consuming, however, and only a few indexes of shape (eg, body girths and their ratios) are used regularly in clinical practice or epidemiology, both of which still rely primarily on body mass index (BMI). Three-dimensional (3-D) body scanning provides high-quality digital information about shape. OBJECTIVES: The objectives of the study were to investigate the relation of shape and BMI and to examine associations between age, sex, and shape. DESIGN: In a cross-sectional study of 9617 adults (45% male) aged 16-91 y who were participating in the UK National Sizing Survey, body girths and their ratios were obtained with the use of a 3-D body scan. Data on weight and height were also obtained. RESULTS: BMI was significantly associated with chest and waist in men and with hips and bust in women. In early adulthood, the sexes differed significantly in shape; however, these differences declined with age. Whereas male shape remained highly stable through adulthood, upper body girths, particularly waist, increased in women, but thigh decreased. After adjustment for other girths, waist was significantly and inversely associated with height, particularly in men. Waist varied widely in both sexes for a given BMI value. CONCLUSIONS: Relations between BMI and shape differed significantly between the sexes, particularly in association with age. The inverse association between height and waist in men suggests either a genetic contribution or a link between early growth pattern and predisposition to obesity. The 3-D scans offer a novel approach for epidemiologic research into associations between body shape and health risks and outcomes. PMID- 17284740 TI - Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: It is often suggested that chronic wasting diseases [eg, chronic obstructive pulmonary disease (COPD)] may benefit from branched-chain amino acid (BCAA) administration via improved protein metabolism. OBJECTIVE: The aim was to examine whether adding BCAAs to a soy protein meal would enhance protein anabolism in COPD patients and in healthy elderly persons. DESIGN: Eight normal weight COPD patients and 8 healthy control subjects were examined on 2 test days. Simultaneous continuous intravenous infusion of l-[ring-(2)H(5)]phenylalanine (Phe) and l-[ring-(2)H(2)]tyrosine tracers was done postabsorptively and at 2 h of ingestion of a maltodextrin soy or maltodextrin soy + BCAA protein meal (rate of ingestion: 0.02 g protein.kg body weight(-1).20 min(-1)) in a crossover design. Together with the meal, oral ingestion of 1-[(13)C]Phe was performed to measure first-pass Phe splanchnic extraction (SPE(Phe)). The endogenous rate of Phe appearance [reflecting whole-body protein breakdown (WbPB)], whole-body protein synthesis (WbPS), and net WbPS (WbPS - WbPB) were calculated. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses. RESULTS: Soy feeding induced a reduction in WbPB and an increase in WbPS. BCAA supplementation of soy protein resulted in a significantly higher (P < 0.05) increase in WbPS than did soy protein alone in COPD patients but not in the healthy elderly. BCAA supplementation did not significantly alter the change in WbPB or net WbPS. Furthermore, BCAA supplementation decreased (absolute) SPE(Phe) (P < 0.05) but did not change the percentage Phe hydroxylation in the splanchnic area, which indicates a BCAA-related reduction in splanchnic protein synthesis. CONCLUSION: BCAA supplementation to soy protein enhances WbPS in patients with COPD and alters interorgan protein metabolism in favor of the peripheral (muscle) compartment in healthy elderly and even more in COPD patients. PMID- 17284742 TI - Response of albumin synthesis to oral nutrients in young and elderly subjects. AB - BACKGROUND: The synthesis of albumin after oral ingestion of nutrients provides a means of storing amino acids, which can be made available during periods of fasting. OBJECTIVE: This study was undertaken to see whether the response of albumin synthesis to the oral intake of nutrients is compromised in elderly subjects. DESIGN: Albumin synthesis was determined from the incorporation of 43 mg l-[(2)H(5)]phenylalanine/kg body wt. Eight elderly subjects (aged >60 y) and 8 young subjects (aged 21-35 y) were studied on 3 separate occasions: after the intake of water, a liquid meal (with 15% of energy from protein, 30% of energy from fat, and 55% of energy from carbohydrate), or an isonitrogenous but not isocaloric meal containing only protein. RESULTS: Mean (+/-SEM) albumin synthesis, expressed as an absolute rate (ie, the amount of albumin synthesized per day), was significantly lower in elderly subjects (108 +/- 7 mg . kg body wt( 1) . d(-1)) than in young subjects (141 +/- 7 mg . kg body wt(-1) . d(-1)). In response to the complete meal, albumin synthesis was significantly increased in both the elderly (144 +/- 7 mgkg body wt(-1) . d(-1)) and the young (187 +/- 11 mg . kg body wt(-1) . d(-1)) subjects. The protein component of the meal was sufficient to stimulate albumin synthesis in both the elderly (147 +/- 14 mg . kg body wt(-1) . d(-1)) and the young (182 +/- 6 mg . kg body wt(-1) . d(-1)) subjects. CONCLUSIONS: Elderly subjects have lower rates of albumin synthesis than do young subjects during fasting, but they stimulate albumin synthesis proportionately in response to the oral ingestion of protein. The intakes of additional fat and carbohydrate do not stimulate albumin synthesis further. PMID- 17284743 TI - Production of stable-isotope-labeled bovine heme and its use to measure heme-iron absorption in children. AB - BACKGROUND: The use of stable isotopes has provided valuable insights into iron absorption in humans, but the data have been limited to nonheme iron. OBJECTIVE: Our objectives were to produce heme iron enriched in (58)Fe and to use it to study the absorption of heme iron and the effect of iron and zinc intakes on heme iron absorption in children. DESIGN: Labeled bovine heme was produced in a bovine model. Forty-eight children were randomly assigned to consume identical meals containing 1 of 3 doses of labeled heme iron (2, 4, or 8 mg as hemoglobin) and 1 of 2 doses of inorganic zinc (1 or 9 mg); successful measurements of iron absorption, zinc absorption, or both were made in 40 of these subjects. We hypothesized that fractional heme-iron absorption would decrease as heme-iron intake increased and that higher zinc intakes would decrease heme-iron absorption. RESULTS: (58)Fe heme was produced with an enrichment (mass/mass) of 9.5%. Fractional iron absorption in children was significantly affected by the intake of heme iron (P = 0.0013) and of zinc (P = 0.0375), but, contrary to expectations, heme-iron absorption was higher at higher zinc intakes. Absolute heme-iron absorption was higher in the group with higher zinc intakes, but only for those with the lowest heme-iron intake (2 mg; P = 0.0147). Although fractional zinc absorption decreased as zinc intake increased (P = 0.031), absolute zinc absorption continued to increase across the intake range studied (P = 0.018). CONCLUSIONS: Heme iron intrinsically labeled with (58)Fe can be produced at sufficient enrichments for use in human studies. In children, heme iron and zinc absorption decrease as the dose of each mineral increases. Heme iron did not inhibit zinc absorption. At lower heme intakes, zinc intakes may increase heme-iron absorption. PMID- 17284741 TI - Plasma concentrations of free triiodothyronine predict weight change in euthyroid persons. AB - BACKGROUND: Factors that influence energy metabolism and substrate oxidation, such as thyroid hormones (THs), may be important regulators of body weight. OBJECTIVE: We investigated associations of THs cross-sectionally with obesity, energy expenditure, and substrate oxidation and prospectively with weight change. DESIGN: Euthyroid, nondiabetic, healthy, adult Pima Indians (n = 89; 47 M, 42 F) were studied. Percentage body fat (%BF) was measured by using dual-energy X-ray absorptiometry; sleeping metabolic rate (SMR), respiratory quotient, and substrate oxidation rates were measured in a respiratory chamber. Thyroid stimulating hormone (TSH), free thyroxine (T(4)), free triiodothyronine (T(3)), and leptin concentrations were measured in fasting plasma samples. RESULTS: TSH, but neither free T(3) nor free T(4), was associated with %BF and leptin concentrations (r = 0.27 and 0.29, respectively; both: P or=65 y) were randomly assigned to receive either a daily supplement containing folate (1 mg), vitamin B-12 (500 microg), and vitamin B-6 (10 mg) or a placebo for 2 y. Of these participants, we selected 135 with baseline homocysteine concentrations >15.0 micromol/L, and we measured serum bone-specific alkaline phosphatase, a marker of bone formation, and bone-derived collagen fragments, a marker of bone resorption, at baseline and 2 y later. RESULTS: At 2 y, plasma homocysteine concentrations were 5.2 mumol/L (95% CI: 3.9, 6.6 micromol/L; P < 0.001) lower in the vitamin than in the placebo group. No significant differences were found in either serum bone-specific alkaline phosphatase (-0.3 microg/L; 95% CI: -2.8, 2.1 microg/L; P = 0.79) or bone-derived collagen fragments (-0.0 microg/L; 95% CI: 0.1, 0.1 microg/L; P = 0.76) between the vitamin and placebo groups, respectively, with 2 y of supplementation. CONCLUSION: Supplementation with folate and vitamins B-6 and B-12 lowered plasma homocysteine but had no beneficial effect on bone turnover at the end of 2 y, as assessed by biomarkers of bone formation and resorption. PMID- 17284745 TI - Bioavailability of food folates is 80% of that of folic acid. AB - BACKGROUND: The bioavailability of natural food folates is lower than that of synthetic folic acid, but no agreement exists as to the extent of the difference. OBJECTIVE: In a 4-wk dietary intervention study, we determined the aggregate bioavailability of food folates from fruit, vegetables, and liver relative to that of folic acid. DESIGN: Seventy-two healthy adults were randomly divided into 4 treatment groups. Group A (n = 29) received a high-folate diet with 369 mug food folate/d and a placebo capsule; groups B, C, and D (n = 14 or 15) received a low-folate diet with 73 microg food folate/d and folic acid capsules. These capsules contained 92 microg folic acid/d for group B, 191 microg for group C, and 289 microg for group D. In addition, all 72 subjects daily ingested a capsule with 58 microg [(13)C(11)]-labeled folic acid. We measured the percentage of [(13)C(11)]-labeled folate in plasma folate at the end of the intervention and ascertained the changes in serum folate concentrations over the 4 wk of the intervention. RESULTS: Bioavailability of food folate relative to that of folic acid was 78% (95% CI: 48%, 108%) according to [(13)C(11)]-labeled folate and 85% (52%, 118%) according to changes in serum folate concentrations. CONCLUSIONS: The aggregate bioavailability of folates from fruit, vegetables, and liver is approximately 80% of that of folic acid. The consumption of a diet rich in food folate can improve the folate status of a population more efficiently than is generally assumed. PMID- 17284746 TI - Effect of the maternal betaE-globin gene on hematologic responses to iron supplementation during pregnancy. AB - BACKGROUND: It is customary in Southeast Asia to treat pregnant anemic women with iron supplements, but anemia in this region may be complicated by thalassemia and hemoglobinopathies, which lead to an ineffective response. OBJECTIVE: The aim was to determine whether routine iron supplementation during pregnancy in this area, which has a high prevalence of thalassemia and hemoglobinopathies, is an effective control strategy for iron deficiency anemia. DESIGN: A prospective study was conducted. Seventy-six pregnant women, including 43 who were heterozygous for the hemoglobin E (Hb E) gene, 20 who were heterozygous for Hb E and had alpha-thalassemia, and 13 who were homozygous Hb E, as well as 77 pregnant women who had no thalassemia gene, participated in this investigation. All pregnant women received a daily dose of 120 mg elemental Fe for an average of 133.5 d. Hematologic variables and serum ferritin concentrations were measured before supplementation and after supplementation at the gestational age of 28-32 wk. Differences in hematologic variables and serum ferritin were assessed. RESULTS: Significant differences in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin responses were found between the nonthalassemia group and the 3 groups with the Hb E gene after adjustment for the following baseline values: age, body mass index, duration of iron supplementation, and ferritin concentration. Significant differences in the improvements in mean corpuscular volume and mean corpuscular hemoglobin values between the 3 groups indicate a poorer response at the cellular level in the pregnant women with the Hb E gene. Further analysis showed a significant difference in the hemoglobin response only for women who were homozygous for Hb E. CONCLUSION: Iron supplementation during pregnancy is not beneficial for pregnant women who are homozygous for Hb E, but a routine intervention should not cause iron overload, as judged from this short observation period. PMID- 17284747 TI - Long-term effects of perinatal nutrition on T lymphocyte kinetics in young Gambian men. AB - BACKGROUND: Nutritional status is highly dependent on season in countries such as The Gambia. In a rural Gambian setting, individuals born during periods of seasonal nutritional deprivation ("hungry seasons") are susceptible to mortality from infectious diseases in adult life. OBJECTIVE: We investigated the hypothesis that impaired immunocompetence in those born in the hungry season results from an underlying defect in immunologic memory, similar to the immunosenescence of old age, which is likely to be reflected in the phenotype and kinetics of T lymphocytes in young adults. DESIGN: T cell phenotype in terms of CD3, CD4, CD8, CD45RA, and CD45R0 expression and in vivo dynamics measured by stable isotope labeling of T cell subsets combined with gas chromatography-mass spectrometry and frequency of T cell receptor excision circles were measured in 25 young (18-24-y old) Gambian men. Thirteen of these 25 men were exposed to perinatal malnutrition as defined by birth season and birth weight. RESULTS: In persons born in the hungry season with low birth weight, no differences in the proportions of memory or naive T cells were found. Kinetic analysis showed higher proliferation rates in memory (CD45R0(+)) subsets of T cells than in naive (CD45R0(-)) cells, which is consistent with previous studies, but no evidence was found for an effect of birth weight or season on T lymphocyte proliferation and disappearance rates. No significant correlations were found between in vivo T cell kinetics and frequency of T cell receptor excision circles. Only absolute numbers of granulocytes were elevated in those born in the nutritionally deprived season. CONCLUSION: In healthy young Gambian men, T lymphocyte homeostasis is extremely robust regardless of perinatal nutritional compromise. PMID- 17284748 TI - Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. AB - BACKGROUND: Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon, but human data supporting this suggestion are weak. OBJECTIVE: The objective was to verify whether the prebiotic concept (selective interaction with colonic flora of nondigested carbohydrates) as induced by a synbiotic preparation-oligofructose enriched inulin (SYN1) + Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (BB12)-is able to reduce the risk of colon cancer in humans. DESIGN: The 12-wk randomized, double-blind, placebo-controlled trial of a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12 was conducted in 37 colon cancer patients and 43 polypectomized patients. Fecal and blood samples were obtained before, during, and after the intervention, and colorectal biopsy samples were obtained before and after the intervention. The effect of synbiotic consumption on a battery of intermediate bio-markers for colon cancer was examined. RESULTS: Synbiotic intervention resulted in significant changes in fecal flora: Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased. The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients. Genotoxicity assays of colonic biopsy samples indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period. Synbiotic consumption prevented an increased secretion of interleukin 2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon gamma in the cancer patients. CONCLUSIONS: Several colorectal cancer biomarkers can be altered favorably by synbiotic intervention. PMID- 17284749 TI - Vitamin A, retinol, and carotenoids and the risk of gastric cancer: a prospective cohort study. AB - BACKGROUND: Vitamin A may influence gastric carcinogenesis through its essential role in controlling cell proliferation and differentiation. However, epidemiologic studies of vitamin A, retinol (preformed vitamin A), and provitamin A carotenoids in relation to the risk of gastric cancer have documented inconsistent results. OBJECTIVE: The objective of the study was to examine the associations between intakes of vitamin A, retinol, and specific carotenoids and the risk of gastric cancer in a prospective population-based cohort study of Swedish adults. DESIGN: The study cohort consisted of 82 002 Swedish adults aged 45-83 y who had completed a food-frequency questionnaire in 1997. The participants were followed through June 2005. RESULTS: During a mean 7.2-y follow up, 139 incident cases of gastric cancer were diagnosed. High intakes of vitamin A and retinol from foods only (dietary intake) and from foods and supplements combined (total intake) and of dietary alpha-carotene and beta-carotene were associated with a lower risk of gastric cancer. The multivariate relative risks for the highest versus lowest quartiles of intake were 0.53 (95% CI: 0.32, 0.89; P for trend = 0.02) for total vitamin A, 0.56 (95% CI: 0.33, 0.95; P for trend = 0.05) for total retinol, 0.50 (95% CI: 0.30, 0.83; P for trend = 0.03) for alpha carotene, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.07) for beta-carotene. No significant associations were found for beta-cryptoxanthin, lutein and zeaxanthin, or lycopene intake. CONCLUSION: High intakes of vitamin A, retinol, and provitamin A carotenoids may reduce the risk of gastric cancer. PMID- 17284750 TI - Watercress supplementation in diet reduces lymphocyte DNA damage and alters blood antioxidant status in healthy adults. AB - BACKGROUND: Cruciferous vegetable (CV) consumption is associated with a reduced risk of several cancers in epidemiologic studies. OBJECTIVE: The aim of this study was to determine the effects of watercress (a CV) supplementation on biomarkers related to cancer risk in healthy adults. DESIGN: A single-blind, randomized, crossover study was conducted in 30 men and 30 women (30 smokers and 30 nonsmokers) with a mean age of 33 y (range: 19-55 y). The subjects were fed 85 g raw watercress daily for 8 wk in addition to their habitual diet. The effect of supplementation was measured on a range of endpoints, including DNA damage in lymphocytes (with the comet assay), activity of detoxifying enzymes (glutathione peroxidase and superoxide dismutase) in erythrocytes, plasma antioxidants (retinol, ascorbic acid, alpha-tocopherol, lutein, and beta-carotene), plasma total antioxidant status with the use of the ferric reducing ability of plasma assay, and plasma lipid profile. RESULTS: Watercress supplementation (active compared with control phase) was associated with reductions in basal DNA damage (by 17%; P = 0.03), in basal plus oxidative purine DNA damage (by 23.9%; P = 0.002), and in basal DNA damage in response to ex vivo hydrogen peroxide challenge (by 9.4%; P = 0.07). Beneficial changes seen after watercress intervention were greater and more significant in smokers than in nonsmokers. Plasma lutein and beta-carotene increased significantly by 100% and 33% (P < 0.001), respectively, after watercress supplementation. CONCLUSION: The results support the theory that consumption of watercress can be linked to a reduced risk of cancer via decreased damage to DNA and possible modulation of antioxidant status by increasing carotenoid concentrations. PMID- 17284752 TI - Heme and non-heme iron consumption and risk of gallstone disease in men. AB - BACKGROUND: Excessive iron intake can promote biliary cholesterol crystal formation in experimental studies. The absorption of heme iron is more complete than that of non-heme iron in humans; however, the effect of long-term consumption of heme and non-heme iron on the risk of gallstones is unknown. OBJECTIVE: The objective of the study was to examine long-term iron intake in relation to the occurrence of gallstone disease. DESIGN: We prospectively studied intakes of heme and non-heme iron and the risk of gallstone disease in a cohort of 44 758 US men from 1986 to 2002. Iron consumption was assessed by using a validated semiquantitative food-frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially. RESULTS: We documented 2468 incident cases of symptomatic gallstones during 597 699 person-years of follow up. The age-adjusted relative risks (RRs) for men with intakes of heme iron and non-heme iron, when the highest and lowest quintiles were compared, were 1.21 (95% CI: 1.06, 1.37; P for trend = 0.0008) and 1.02 (95% CI: 0.90, 1.16; P for trend = 0.45), respectively. After adjustment for multiple potential confounding variables, when extreme quintiles were compared, the multivariate RR of heme iron intake was not significantly changed and remained significant with a dose response relation (RR = 1.21; 95% CI: 1.03, 1.42; P for trend = 0.01), and that of non-heme iron intake was not significant (RR = 1.14; 95% CI: 0.99, 1.31; P for trend = 0.18). CONCLUSION: Our findings suggest that a higher consumption of heme iron is associated with a greater risk of gallstone disease among men. PMID- 17284751 TI - Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging. AB - BACKGROUND: High concentrations of homocysteine have been linked to a greater risk of Alzheimer disease, dementia, and cognitive decline. OBJECTIVE: We evaluated the association between homocysteine and 4.5-y combined incidences of dementia and cognitive impairment without dementia (CIND) in a cohort of 1779 Mexican Americans aged 60-101 y. DESIGN: Homocysteine, red blood cell (RBC) folate, and plasma vitamin B-12 were measured at baseline. New cases of dementia or CIND were ascertained by neuropsychological and clinical examinations and expert adjudication. We used proportional hazards models to estimate the risk of homocysteine-associated dementia or CIND and the influence of RBC folate and plasma vitamin B-12 on that association. RESULTS: High homocysteine concentrations were associated with a greater risk of dementia or CIND: hazard ratio (HR): 2.39; 95% CI: 1.11, 5.16. Plasma vitamin B-12 modified the association between homocysteine and the outcome. The rates of dementia or CIND associated with homocysteine for those in the lowest and highest tertiles of vitamin B-12, respectively, were significantly higher (HR: 1.61, P = 0.04) and lower (HR: 0.94, P = 0.015) than the risk for those in the middle tertile. CONCLUSIONS: Homocysteine is an independent risk factor for both dementia and CIND. Higher plasma vitamin B-12 may reduce the risk of homocysteine-associated dementia or CIND. PMID- 17284754 TI - Maternal diet during pregnancy in relation to eczema and allergic sensitization in the offspring at 2 y of age. AB - BACKGROUND: Maternal diet during pregnancy might be one of the factors that influences fetal immune responses associated with childhood allergy. OBJECTIVE: We analyzed the association between maternal diet during the last 4 wk of pregnancy and allergic sensitization and eczema in the offspring at 2 y of age. DESIGN: Data from 2641 children at 2 y of age were analyzed within a German prospective birth cohort study (LISA). Maternal diet during the last 4 wk of pregnancy was assessed with a semiquantitative food-frequency questionnaire, which was administered shortly after childbirth. RESULTS: High maternal intake of margarine [adjusted odds ratio (aOR): 1. 49; 95% CI: 1.08, 2.04] and vegetable oils (aOR: 1.48; 95% CI: 1.14, 1.91) during the last 4 wk of pregnancy was positively associated and high maternal fish intake (aOR: 0.75; 95% CI: 0.57, 0.98) was inversely associated with eczema during the first 2 y in the offspring. High celery (aOR: 1.85; 95% CI: 1.18, 2.89) and citrus fruit (aOR: 1.73; 95% CI: 1.18, 2.53) intakes increased the risk of sensitization against food allergens. In turn, sensitization against inhalant allergens was positively related to a high maternal intake of deep-frying vegetable fat (aOR: 1.61; 95% CI: 1.02, 2.54), raw sweet pepper (aOR: 2.16; 95% CI: 1.20, 3.90), and citrus fruit (aOR: 1.72; 95% CI: 1.02, 2.92). CONCLUSIONS: We suggest that the intake of allergenic foods and foods rich in n-6 polyunsaturated fatty acids during pregnancy may increase and foods rich in n-3 polyunsaturated fatty acids may decrease the risk of allergic diseases in the offspring. PMID- 17284753 TI - Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men. AB - BACKGROUND: Nutrients with antioxidant properties or that influence cell growth and differentiation might reduce the risk of benign prostatic hyperplasia (BPH). OBJECTIVE: The objective was to evaluate the association of fruit, vegetable, and micronutrient intakes with BPH. DESIGN: The participants were members of the Health Professionals Follow-Up Study and were aged 46-81 y in 1992. In 1992 and biennially thereafter, the men reported having surgery for an enlarged prostate, and in 1992 and on 3 subsequent questionnaires they completed the American Urological Association symptom index (AUASI). BPH cases were men who reported having surgery or who had an AUASI score of 15-35 (n = 6092). Control subjects were men who had not had surgery and never had an AUASI score >7 (n = 18 373). Men with a score of 8-14 were excluded (n = 7800). Intakes of fruit, vegetables, and antioxidants were assessed with a food-frequency questionnaire in 1986. We calculated odds ratios (ORs) of BPH and 95% CIs using logistic regression. RESULTS: Vegetable consumption was inversely associated with BPH (fifth compared with first quintile-OR: 0.89; 95% CI: 0.80, 0.99; P for trend = 0.03), whereas fruit intake was not. Consumption of fruit and vegetables rich in beta-carotene (P for trend = 0.004), lutein (P for trend = 0.0004), or vitamin C (P for trend = 0.05) was inversely related to BPH. With increasing vitamin C intake from foods, men were less likely to have BPH (P for trend = 0.0009). Neither alpha- nor gamma tocopherol intake from foods was associated with BPH (P for trend = 0.05 and 0.84, respectively). CONCLUSION: Our findings are consistent with the hypothesis that a diet rich in vegetables may reduce the occurrence of BPH. PMID- 17284755 TI - Comparison of the effects of zinc delivered in a fortified food or a liquid supplement on the growth, morbidity, and plasma zinc concentrations of young Peruvian children. AB - BACKGROUND: Zinc supplementation decreases morbidity from infections and increases growth of stunted children, but there is little information on functional responses to zinc delivered in fortified foods. OBJECTIVE: The aim was to examine the effects of zinc fortification on the growth, morbidity from infections, and plasma zinc concentrations of young children. DESIGN: We compared the physical growth, morbidity, and micronutrient status of 6-8-mo-old Peruvian children with initial length-for-age z score (LAZ) < -0.50 who were randomly assigned to receive one of the following treatments daily for 6 mo: 1) 30 g dry weight of an iron-fortified cereal porridge and a separate dose of an aqueous multivitamin (MV) supplement between meals (control group), 2) the same porridge and MV with 3 mg Zn added to the supplement dose (ZnSuppl group), or 3) the porridge with added zinc (150 mg/kg dry weight) and MV without zinc (ZnFort group). RESULTS: The children consumed a mean of 22-26 g dry porridge/d and 96% of the possible MV doses. After adjustment for small baseline differences in socioeconomic status and morbidity, no significant differences in weight or length increments were observed between the groups, even among the subset with an initial LAZ < -1.5, and no significant differences in the rates of common illnesses were observed. Mean plasma zinc concentrations decreased in the control group (-3.9 microg/dL), increased in the ZnSuppl group (4.3 microg/dL), and did not change significantly in the ZnFort group (-1.5 microg/dL; P < 0.001 for group wise comparison). CONCLUSIONS: Provision of additional zinc, either in an aqueous supplement or a fortified porridge, did not significantly affect the children's physical growth or morbidity from infections, possibly because they were not sufficiently growth-restricted or zinc-deficient initially or because the level of zinc intake or absorption was inadequate. Additional studies of the functional effect of zinc-fortified foods are needed in populations that are known to respond to zinc supplements. PMID- 17284756 TI - Reproducibility and validity of dietary glycemic index, dietary glycemic load, and total carbohydrate intake in 141 Swedish men. AB - BACKGROUND: Although the associations of dietary glycemic index (GI) and dietary glycemic load (GL) with many chronic diseases have been examined in epidemiologic studies, information regarding the reproducibility and validity of these measures assessed with the use of food-frequency questionnaires (FFQs) is lacking. OBJECTIVE: We examined the reproducibility and validity of dietary GI and dietary GL and of carbohydrate intake as assessed by using an FFQ. DESIGN: Swedish men (n = 141) aged 40-74 y completed 2 FFQs 1 y apart and two 1-wk weighed diet records 6 mo apart. Dietary GI, dietary GL, and carbohydrate intake (starches and sugars) were calculated from both FFQs and diet records. We used intraclass correlations between the 2 FFQs to measure reproducibility and Pearson correlations between the diet records and the FFQs to assess the relative validity. RESULTS: Reproducibility of the FFQs was 0.66 (95% CI: 0.56, 0.75) for dietary GI, 0.61 (95% CI: 0.50, 0.71) for dietary GL, and 0.61 (95% CI: 0.50, 0.71) for carbohydrate. The correlations between the FFQs and diet records were 0.62 (95% CI: 0.45, 0.74) for dietary GI, 0.77 (95% CI: 0.56, 0.88) for dietary GL, and 0.76 (95% CI: 0.55, 0.88) for carbohydrate after adjustment for within-person variation in the FFQs and diet records. CONCLUSION: In this sample of men, an FFQ measured dietary GI, dietary GL, and carbohydrate with reproducibility and validity similar to other commonly studied nutritional factors. PMID- 17284757 TI - alpha-Linolenic acid, Delta6-desaturase gene polymorphism, and the risk of nonfatal myocardial infarction. AB - BACKGROUND: Delta(6)-Desaturase (FADS2) is the rate-limiting step in the polyunsaturated fatty acid (PUFA) biosynthetic pathway. OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of FADS2 affects the PUFA biosynthetic pathway and consequently modifies the effect of alpha-linolenic acid (ALA) on myocardial infarction (MI). DESIGN: Case subjects (n =1694) with a first nonfatal acute MI were matched by age, sex, and area of residence to 1694 population-based control subjects in Costa Rica. PUFAs were quantified by gas liquid chromatography from plasma and adipose tissue samples. Least-squares means from generalized linear models and odds ratios (ORs) and 95% CIs from multiple conditional logistic regression models were estimated. RESULTS: The prevalence of the variant T/- allele was 48%. Eicosapentaenoic acid, gamma-linolenic acid, and arachidonic acid decreased in adipose tissue and plasma with increasing number of copies of the variant allele with a monotonic trend (P < 0.05 for all). Fasting plasma triacylglycerols by genotype were 2.08 mmol/L for TT, 2.16 mmol/L for T-, and 2.26 mmol/L for - - [ie, homozygous for the variant (deletion) allele] (P = 0.03). The FADS2 deletion was not associated with MI and did not significantly modify the association between adipose tissue ALA and the risk of MI. CONCLUSIONS: The FADS2 deletion may prevent the conversion of ALA into very-long chain PUFAs. However, this metabolic effect is not translated into an attenuated risk between ALA and MI among carriers of the variant. It is possible that, at current intakes of ALA, any potential defect in the transcription of the gene is masked by the availability of substrate. Further research in populations deficient in ALA intake is warranted. PMID- 17284758 TI - Dietary sialic acid supplementation improves learning and memory in piglets. AB - BACKGROUND: Sialic acid, a key component of both human milk oligosaccharides and neural tissues, may be a conditional nutrient during periods of rapid brain growth. OBJECTIVE: We tested the hypothesis that variations in the sialic acid content of a formula milk would influence early learning behavior and gene expression of enzymes involved in sialic acid metabolism in piglets. DESIGN: Piglets (n = 54) were allocated to 1 of 4 groups fed sow milk replacer supplemented with increasing amounts of sialic acid as casein glycomacropeptide for 35 d. Learning performance and memory were assessed with the use of easy and difficult visual cues in an 8-arm radial maze. Brain ganglioside and sialoprotein concentrations and mRNA expression of 2 learning-associated genes (ST8SIA4 and GNE) were measured. RESULTS: In both tests, the supplemented groups learned in significantly fewer trials than did the control group, with a dose-response relation for the difficult task (P = 0.018) but not the easy task. In the hippocampus, significant dose-response relations were observed between amount of sialic acid supplementation and mRNA levels of ST8SIA4 (P = 0.002) and GNE (P = 0.004), corresponding with proportionate increases in protein-bound sialic acid concentrations in the frontal cortex. CONCLUSIONS: Feeding a protein-bound source of sialic acid during early development enhanced learning and increased expression of 2 genes associated with learning in developing piglets. Sialic acid in mammalian milks could play a role in cognitive development. PMID- 17284759 TI - Maternal nutrition and optimal infant feeding practices: executive summary. AB - Much recent attention has been paid to the effect of the fetal environment on not only healthy birth outcomes but also long-term health outcomes, including a role as an antecedent to adult diseases. A major gap in our understanding of these relations, however, is the effect of maternal nutrition and nutrient transport on healthy fetal growth and development. In addition, this gap precludes evidence based recommendations about how to best feed preterm infants. The biological role of the mother and the effect of her nutritional status on infant feeding extend to postnatal infant feeding practices. Currently, evidence is incomplete about not only the composition of human milk, but also the maternal nutritional needs to support extended lactation and the appropriate nutrient composition of foods that will be used to complement breastfeeding at least through the first year of life. Consequently, a conference, organized by the National Institute of Child Health and Human Development, the National Institutes of Health Office of Dietary Supplements, and the US Department of Agriculture Children's Nutrition Research Center was held to explore current knowledge and develop a research agenda to address maternal nutrition and infant feeding practices. These proceedings contain presentations about the effect of maternal nutrition and the placental environment on fetal growth and birth outcomes, as well as issues pertaining to feeding preterm and full-term infants. PMID- 17284760 TI - Low birth weight in the United States. AB - Pregnancy outcomes in the United States and other developed countries are considerably better than those in many developing countries. However, adverse pregnancy outcomes are generally more common in the United States than in other developed countries. Low-birth-weight infants, born after a preterm birth or secondary to intrauterine growth restriction, account for much of the increased morbidity, mortality, and cost. Wide disparities exist in both preterm birth and growth restriction among different population groups. Poor and black women, for example, have twice the preterm birth rate and higher rates of growth restriction than do most other women. Low birth weight in general is thought to place the infant at greater risk of later adult chronic medical conditions, such as diabetes, hypertension, and heart disease. Of interest, maternal thinness is a strong predictor of both preterm birth and fetal growth restriction. However, in the United States, several nutritional interventions, including high-protein diets, caloric supplementation, calcium and iron supplementation, and various other vitamin and mineral supplementations, have not generally reduced preterm birth or growth restriction. Bacterial intrauterine infections play an important role in the etiology of the earliest preterm births, but, at least to date, antibiotic treatment either before labor for risk factors such as bacterial vaginosis or during preterm labor have not consistently reduced the preterm birth rate. Most interventions have failed to reduce preterm birth or growth restriction. The substantial improvement in newborn survival in the United States over the past several decades is mostly due to better access to improved neonatal care for low-birth-weight infants. PMID- 17284761 TI - Placental transport: a function of permeability and perfusion. AB - Studies in ovine fetus and placenta have pointed to an interaction between the fetal liver and the placenta. The supply of amino acids and carbohydrates depends on this interaction. These studies have led to clinical studies in normal and high-risk pregnancies. The objective of the present review was to compare changes in fetal circulation, in terms of both velocimetry and actual blood flow measurements, and to couple such data with data on the placental transport of amino acids. Flow studies were carried out on the umbilical vein with measurements of time-averaged velocity and venous diameter. A similar approach was used for measurements of ductus venosus flow. Stable-isotope-labeled amino acids were used to study placental transport by the non-steady state approach. The studies of flow showed a marked reduction in umbilical blood flow even when expressed per kilogram fetal body weight in fetal-growth-restricted pregnancies. This may be coupled with an increased ductus venosus shunt, the combination leading to a marked reduction in fetal hepatic blood flow. The placental transport of some amino acids is reduced in fetal-growth-restricted pregnancies. Furthermore, nonglucose carbohydrates and polyols are found in fetal blood, some in concentrations higher than maternal concentrations. There is significant uptake of several polyols and of mannose across the umbilical circulation in normal pregnancies. In conclusion, both perfusion and permeability can now be studied in both normal and high-risk pregnancies. PMID- 17284763 TI - In utero physiology: role in nutrient delivery and fetal development for calcium, phosphorus, and vitamin D. AB - Only limited aspects of the transfer of calcium across the placenta to the fetus are known. Clinical outcome studies suggest that bone mineral mass in newborn infants is related to maternal size and dairy intake. Available data indicate that vitamin D deficiency may also limit in utero fetal bone mineral accumulation. Recent data suggest that maternal vitamin D status affects long term childhood bone status. At present, no strong evidence exists showing that improving maternal calcium or vitamin D status has a long-term positive effect on childhood bone mass. In premature infants, clinical rickets and fractures are common. In utero rates of calcium accretion during the third trimester cannot be readily achieved. The use of fortifiers designed for human-milk-fed infants or specially designed high-mineral-containing formulas allows for bone mineral accretion at or near in utero rates. Recent data have shown that physical therapy programs, judiciously used, in combination with adequate mineral content, can enhance bone mineral mass in preterm infants. There is little evidence for the use of high doses of vitamin D in the management of premature infants. After hospital discharge, continuation of a relatively high mineral intake has been shown to enhance bone mineral acquisition. Future research should include evaluations of the role of maternal vitamin D supplementation on fetal and infant bone mass, the mineral needs of infants weighing <800 g or <25 wk gestation, and the optimal discharge management of premature infants who are at risk of low bone mass. PMID- 17284762 TI - In utero physiology: role of folic acid in nutrient delivery and fetal development. AB - Despite the isolation of placental folate receptors 25 y ago and progress in defining the mechanism of folate delivery, considerable gaps remain in the literature for each level of the maternal-placental-fetal unit. Although a critical role of placental folate receptors in maternal-to-fetal folate transport was shown by use of the isolated perfused-placental cotyledon model a decade ago, in vivo confirmation is still needed. Knockout of folate receptors in mice, and knock-down of folate receptors by delivery of antisense oligonucleotides at gestation day 8 or antibodies to folate receptor, results in profound developmental abnormalities in the fetus, ranging from neural tube defects to neurocristopathies such as cleft-lip and cleft-palate, cardiac septal defects, and eye defects. These abnormalities can be prevented by ensuring the entry of folate into cells via alternative pathways. Controlled dietary folate restriction studies also identified adverse effects on reproductive performance, implantation, and fetal growth and other subtler (microscopic) defects in murine fetal development. Longitudinal follow-up showed that gestational folate deficiency results in behavioral changes-an anxiety phenotype-during adulthood in these mice, which supports the Barker hypothesis. The extent to which these findings are relevant to humans is unclear, however. Nevertheless, the high incidence of neural tube defects among North Indian women, who chronically subsist on one-third to one-half of the optimum folate needed to prevent birth defects, underscores the magnitude of the public health problem and emphasizes the urgent challenge to define the most efficient way to ensure adequate dietary folate for hundreds of millions of such women at risk in developing countries. PMID- 17284764 TI - Can extrauterine growth approximate intrauterine growth? Should it? AB - Most studies evaluating the growth of preterm infants use the so-called intrauterine growth curve and reference fetus as standards. These curves might not be the optimal standards, however, for several reasons. The curves were constructed from small numbers of infants with uncertainty about gestational age, reasons for preterm birth, and, for body-composition data, the reasons for the death of the infant. Second, preterm infants after birth are not comparable with fetuses, being in a completely different environment and receiving a completely different nutrition. For instance, a higher percentage of body fat in preterm infants might well be an adequate adaptation to their environment. To get preterm infants to adhere to their supposed growth curve percentile, catch-up growth is needed. Recent studies indicate that catch-up growth might be advantageous for brain development. It might at the same time increase the incidence of cardiovascular disease in later life. The use of intrauterine growth curves to evaluate postnatal growth needs a critical reevaluation. PMID- 17284765 TI - Nutrition and the developing brain: nutrient priorities and measurement. AB - Nutrients and growth factors regulate brain development during fetal and early postnatal life. The rapidly developing brain is more vulnerable to nutrient insufficiency yet also demonstrates its greatest degree of plasticity. Certain nutrients have greater effects on brain development than do others. These include protein, energy, certain fats, iron, zinc, copper, iodine, selenium, vitamin A, choline, and folate. The effect of any nutrient deficiency or overabundance on brain development will be governed by the principle of timing, dose, and duration. The ability to detect the specific effects of nutrient deficiencies is dependent on knowing which area of the brain is preferentially affected and on having neurologic assessments that tap into the functions of those specific areas. As examples, protein-energy malnutrition causes both global deficits, which are testable by general developmental testing, and area-specific effects on the hippocampus and the cortex. Iron deficiency alters myelination, monoamine neurotransmitter synthesis, and hippocampal energy metabolism in the neonatal period. Assessments of these effects could include tests for speed of processing (myelination), changes in motor and affect (monoamines), and recognition memory (hippocampus). Zinc deficiency alters autonomic nervous system regulation and hippocampal and cerebellar development. Long-chain polyunsaturated fatty acids are important for synaptogenesis, membrane function, and, potentially, myelination. Overall, circuit-specific behavioral and neuroimaging tests are being developed for use in progressively younger infants to more accurately assess the effect of nutrient deficits both while the subject is deficient and after recovery from the deficiency. PMID- 17284766 TI - Regulation of proteolysis and optimal protein accretion in extremely premature newborns. AB - Growth outcomes for extremely premature infants remain poor, and improving growth in this population will require a better understanding of how to limit proteolysis and promote protein accretion. Extremely premature infants exhibit high rates of proteolysis that are unrestrained by physiologic increases in insulin, intravenous amino acids, and full parenteral nutrition. Imbalances in current amino acid solutions may be in part responsible for the inability of parenteral nutrition to reduce proteolysis in preterm infants. However, amino acids in parenteral nutrition are effective for increasing protein synthesis in extremely preterm infants, which leads to improved protein balance. Current evidence suggests that early administration of 3 g amino acids kg(-1)d(-1) to extremely premature infants is safe and effective. Enteral nutrition may be more effective than parenteral nutrition in limiting proteolysis and producing protein accretion in preterm infants, but the protein content of current preterm formulas may be inadequate for supporting optimal growth in this population. Important areas of future research include determining whether altered intravenous amino acid solutions can better effect reductions in proteolysis, investigating the effect of enteral nutrition on proteolysis and protein accretion, and conducting a large randomized controlled trial of formula with a higher protein content. PMID- 17284767 TI - Evaluation of the evidence to support current recommendations to meet the needs of premature infants: the role of human milk. AB - The beneficial effects of human milk extend to the feeding of premature infants, because their nutrition support must be designed to compensate for metabolic and gastrointestinal immaturity, immunologic compromise, and maternal psychosocial conditions. Significant effects on the recipient host, such as reduction in sepsis and necrotizing enterocolitis, have been reported for premature infants fed their mothers' milk. However, nutritional concerns arise because the quantity of nutrients in breast milk may not meet the great nutrient needs of premature infants born weighing <1500 g. Human milk supplements, or fortifiers, are available to augment the nutrient content of unfortified breast milk. Host defense benefits observed in infants fed unfortified human milk also are found in premature infants fed fortified human milk. Availability of milk is an issue for mothers delivering prematurely. Donor pasteurized human milk has been suggested as a proxy for the mother's own milk. PMID- 17284768 TI - Gastrointestinal development and meeting the nutritional needs of premature infants. AB - The fear of necrotizing enterocolitis and feeding intolerance are major factors inhibiting the use of the enteral route as the primary means of nourishing premature infants. Parenteral nutrition may help to meet many of the nutritional needs of these infants, but has significant detrimental side effects that include intestinal atrophy, sepsis, and increased susceptibility to inflammatory stimuli and systemic inflammatory responses. Being able to minimize the use of the parenteral route and still maintain appropriate nutrition safely would be a major advance in neonatology. At the basis of our inability to use the enteral route is a poorly understood immature gastrointestinal tract. Approaches such as minimal enteral nutrition or trophic feedings may partially alleviate these problems. However, if we are to progress in greater utilization of the gastrointestinal tract, other factors need to be considered. These include the macronutrient composition of minimal enteral or trophic feedings and the microecology of the intestinal lumen. Some of the developmental aspects of the intestine, which include intestinal growth, motor activity, barrier and other innate immune functions, and the microecology of the developing intestine, are briefly reviewed here. The purpose of this review is to suggest important areas of future research in neonatal and developmental gastroenterology that could affect several conditions that are related to immaturity of the gastrointestinal tract. PMID- 17284769 TI - Optimal duration of exclusive breastfeeding: what is the evidence to support current recommendations? AB - Before 2001, the World Health Organization (WHO) recommended that infants be exclusively breastfed for 4-6 mo with the introduction of complementary foods (any fluid or food other than breast milk) thereafter. In 2001, after a systematic review and expert consultation, this advice was changed, and exclusive breastfeeding is now recommended for the first 6 mo of life. The systematic review commissioned by the WHO compared infant and maternal outcomes for exclusive breastfeeding for 3-4 mo versus 6 mo. That review concluded that infants exclusively breastfed for 6 mo experienced less morbidity from gastrointestinal infection and showed no deficits in growth but that large randomized trials are required to rule out small adverse effects on growth and the development of iron deficiency in susceptible infants. Others have raised concerns that the evidence is insufficient to confidently recommend exclusive breastfeeding for 6 mo for infants in developed countries, that breast milk may not meet the full energy requirements of the average infant at 6 mo of age, and that estimates of the proportion of exclusively breastfed infants at risk of specific nutritional deficiencies are not available. Additionally, virtually no data are available to form evidence-based recommendations for the introduction of solids in formula-fed infants. Given increasing evidence that early nutrition and growth have effects on both short- and longer-term health, it is vital that this issue be investigated in high-quality randomized studies. Meanwhile, the consequences of the WHO recommendation should be monitored in different settings to assess compliance and record and act on adverse events. The policy should then be reviewed in the context of new data to formulate evidence-based recommendations. PMID- 17284770 TI - Complementary feeding: clinically relevant factors affecting timing and composition. AB - Exclusive breastfeeding for the first 6 mo of life followed by optimal complementary feeding are critical public health measures for reducing and preventing morbidity and mortality in young children. Clinical factors, such as birth weight, prematurity, and illness, that affect the iron and zinc requirements of younger infants are discussed. Maternal diet and nutritional status do not have a strong effect on the mineral content of human milk, but physiologic changes in milk and the infants' status determine the dependence of the infant on complementary foods in addition to human milk to meet iron and zinc requirements after 6 mo. The nature of zinc absorption, which is suitably characterized by saturation response modeling, dictates that plant-based diets, which are low in zinc, are associated with low absolute daily absorbed zinc, which is inadequate to meet requirements. Foods with a higher zinc content, such as meats, are much more likely to be sufficient to meet dietary requirements. Current plant-based complementary feeding patterns for older fully breastfed infants in both developed and developing countries pose a risk of zinc deficiency. The strong rationale for the potential benefits of providing meat as an early complementary food, and the examples of successful intervention programs, provide potent incentives to pursue broader implementation programs, with concurrent rigorous evaluation of both efficacy and effectiveness. PMID- 17284771 TI - Effects of age and gender on micronucleus and chromosome nondisjunction frequencies in centenarians and younger subjects. AB - Studies have shown a significant increase in chromosome aneuploidy with age. The aim of this study was to elucidate whether the age-related changes in the level of hypoploidy correlate with the occurrence of micronuclei (MN) and chromosome nondisjunction (ND) in men and women. We analyzed cytokinesis-blocked (binucleated) lymphocytes treated with cytochalasin B, from 127 donors varying in gender and age including 53 centenarians. Fluorescent in situ hybridization with probes specific for several autosomes (1, 4, 6, 8, 20) and for the sex chromosomes was applied to analyze the chromosomal content of MN and to analyze the frequency of reciprocal loss and gain due to ND in binucleated interphase cells. The general level of MN in Giemsa-stained preparations was higher in women and in both genders increased with age until approximately 70 years and ranged, depending on age group, from 0.5 to 1.4% in men and from 0.9 to 1.8% in women. Gender-related differences were mostly observed in the younger age groups (< or =50 years), with an almost two-fold difference between men and women (P < 0.005). Frequencies of autosome-positive MN in both genders and of sex chromosome positive MN in men were comparable and remained unchanged in older groups. The frequency of X-positive MN in women was higher than the average frequency of autosome-positive MN and continued to increase until the oldest age. The frequency of NDs involving the analyzed chromosomes was on average two-fold higher in women than in men. In both genders, the frequency of NDs increased with age and was, on average, an order of magnitude higher than that of cells with MN, consistent with the previous reports that the efficiency of elimination of micronucleated cells is higher than of the cells presenting chromosome ND. PMID- 17284772 TI - Induction of DNA strand breaks and oxidative stress in HeLa cells by ethanol is dependent on CYP2E1 expression. AB - Induction of cytochrome P4502E1 (CYP2E1) is considered to be an important mechanism by which ethanol can cause toxicity related to oxidative stress both in vivo and in vitro. In the current study, we used HeLa cells with doxycycline regulated CYP2E1 expression to test the hypothesis that induction of CYP2E1 could lead to secondary DNA oxidation that could potentially contribute to the carcinogenicity of ethanol in vivo. Overexpression of CYP2E1 protein was not associated with oxidative stress per se as assessed by markers of lipid peroxidation (cis-parinaric acid oxidation), glutathione depletion and elevation of intracellular reactive oxygen species (dichlorofluoroscin oxidation) in the presence or absence of ethanol substrate (10 mM, 24 h). Furthermore, there was no evidence of elevation of frequency of DNA strand breaks as assessed by the comet assay. In contrast, however, after pre-incubation of cells with L-buthionine (S,R)-sulphoximine (BSO, 10 microM) which caused a 75% reduction in intracellular reduced glutathione (GSH) levels, CYP2E1 expression resulted in oxidative stress as assessed by all of these markers and DNA strand breaks but only in the presence of ethanol (10 mM). No effect was observed under these conditions in control cells not expressing CYP2E1. Furthermore, these effects could be attenuated by co-incubation with 1-aminobenzotriazole (0.5 mM), a suicide inhibitor of P450 activity. In conclusion, in this in vitro model CYP2E1-mediated interaction with ethanol results in the intracellular oxidative stress and the formation of DNA strand breaks which are detectable in cells pre-sensitized by depletion of intracellular levels of GSH. PMID- 17284773 TI - Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors. AB - While the field of cancer genetics has enjoyed a great deal of attention among cancer researchers in the last few decades, the appreciation of cancer epigenetics is more recent, -owing to the fact that epigenetic mechanisms have emerged as key mechanisms in cancer development. All critical changes in cancer cells, such as silencing of tumour-suppressor genes, activation of oncogenes and defects in DNA repair, are caused not only by genetic but also by epigenetic mechanisms. Epigenetic events can affect many steps in tumour development; therefore, better understanding of epigenetic mechanisms is fundamental to our ability to successfully prevent, diagnose and treat cancer. Various environmental and dietary agents and lifestyles are suspected to be implicated in the development of a wide range of human cancers by eliciting epigenetic changes, though the contribution of epigenetic mechanisms to a given human cancer type and the precise targets of epigenetic alterations during cancer development are largely unknown. The major obstacle in establishing a relationship between epigenetic changes and exposure to dietary, lifestyle and environmental factors and cancer is the fact that studies are typically too small and lack statistical power to identify the interactions between epigenetic changes and exposures. Tremendous advances in our understanding of basic epigenetic mechanisms and rapid progress that is being made in developing new powerful technologies, such as those for sensitive and quantitative detection of epigenetic changes as well as for genome-wide analysis (epigenomics), hold great promise that these issues may be addressed in near future. Therefore, experimental evidence on the precise role of epigenetic changes induced by environment, diet and lifestyle is eagerly awaited. PMID- 17284774 TI - Comparison of the peripheral blood micronucleus test using flow cytometry in rat and mouse exposed to aneugens after single-dose applications. AB - Detection of clastogenic compounds in the peripheral blood micronucleus test (MNT) in rats is a well-established methodology. However, the results obtained on the induction of micronuclei by aneugens in rat peripheral blood are controversial. Our aim was a comparative evaluation of the peripheral blood flow cytometry MNT in Wistar Han rat and CD1 mouse exposed to three aneugens (vinblastine, vincristine and colchicine) after single-dose applications. In addition, the same compounds were tested in the rat bone marrow MNT. The treatment with vinblastine (0.25, 0.5, 1, mg/kg), vincristine (0.025, 0.05, 0.1 mg/kg) or colchicine (0.7, 1, 1.3 mg/kg) induced no statistically significant increase in MN-PCEs (micronucleated polychromatic erythrocytes or reticulocytes) in rat peripheral blood. In rat bone marrow, a clear statistically significant increase in MN-PCE was found with vincristine and vinblastine. However, colchicine showed a clear increase in MN-PCE frequency without reaching statistically significant level only at 1 mg/kg. The positive effect in the bone marrow MNT shows that the target organ was exposed to the appropriate concentration levels of the respective aneugens. In mouse, the peripheral blood flow cytometry analysis after the treatment with vinblastine, vincristine and colchicine showed clear statistically significant increase in MN-PCE with all three compounds. The experiments with splenectomized rats treated with vincristine and colchicine were performed and statistically significant increases in MN-PCE were found with 0.05, 0.1, 0.15 mg/kg of vincristine and 0.7 and 1 mg/kg of colchicine. Our results demonstrate that micronucleated cells induced by aneugens are removed from rat peripheral blood by the spleen due to the large size of micronuclei. Based on our data, it is concluded that the flow cytometry peripheral blood MNT after single-dose applications is an appropriate test system for evaluating the genotoxic effects of aneugens in mice. However, in rats peripheral blood MNT aneugen detection might require multiple-dose applications to overwhelm the spleen effect. PMID- 17284775 TI - In vitro susceptibilities in lymphocytes from mothers and cord blood to the monofunctional alkylating agent EMS. AB - It has been reported that children may experience different levels of chemical exposures than adults and that their sensitivities to chemical toxins may be increased or decreased when compared to adults. The perinatal period is one period in which these susceptibilities may be examined. Midwives at the Bradford Royal Infirmary collected venous blood samples from mothers at the time of birth and venous cord blood post-delivery. Lymphocytes were isolated from both blood types and examined in the alkaline comet assay using the monofunctional alkylating agent ethyl methanesulphonate (EMS). There were no biologically significant differences when subjects were categorized into subgroups based on lifestyle habits and physical characteristics, and overall there were no statistically significant differences in levels of DNA damage in mothers (n=22) and babies (n=22), except at the basal level (P<0.05), but mean values in babies were always lower over the EMS dose range. Whole blood was used in the micronucleus (MN) assay, and there was a significantly (P<0.05) higher rate of MN in mothers (n=17), per 1000 binucleates, as compared with lymphocytes from their offspring (n=17) at the basal level. This may be accounted for by age and endogenous factors. Overall, this current study cannot provide statistically significant evidence that children have either increased or decreased levels of susceptibility to a chemical toxin in comparison to adults when EMS is examined in vitro. PMID- 17284776 TI - Influence of major structural features of tocopherols and tocotrienols on their omega-oxidation by tocopherol-omega-hydroxylase. AB - Human cytochrome P450 4F2 (CYP4F2) catalyzes the initial omega-hydroxylation reaction in the metabolism of tocopherols and tocotrienols to carboxychromanols and is, to date, the only enzyme shown to metabolize vitamin E. The objective of this study was to characterize this activity, particularly the influence of key features of tocochromanol substrate structure. The influence of the number and positions of methyl groups on the chromanol ring, and of stereochemistry and saturation of the side chain, were explored using HepG2 cultures and microsomal reaction systems. Human liver microsomes and microsomes selectively expressing recombinant human CYP4F2 exhibited substrate activity patterns similar to those of HepG2 cells. Although activity was strongly associated with substrate accumulation by cells or microsomes, substantial differences in specific activities between substrates remained under conditions of similar microsomal membrane substrate concentration. Methylation at C5 of the chromanol ring was associated with markedly low activity. Tocotrienols exhibited much higher Vmax values than their tocopherol counterparts. Side chain stereochemistry had no effect on omega-hydroxylation of alpha-tocopherol (alpha-TOH) by any system. Kinetic analysis of microsomal CYP4F2 activity revealed Michaelis-Menten kinetics for alpha-TOH but allosteric cooperativity for other vitamers, especially tocotrienols. Additionally, alpha-TOH was a positive effector of omega hydroxylation of other vitamers. These results indicate that CYP4F2-mediated tocopherol-omega-hydroxylation is a central feature underlying the different biological half-lives, and therefore biopotencies, of the tocopherols and tocotrienols. PMID- 17284777 TI - Molecular characterization of cDNA encoding resistance gene-like sequences in Buchloe dactyloides. AB - Current knowledge of resistance (R) genes and their use for genetic improvement in buffalograss (Buchloe dactyloides [Nutt.] Engelm.) lag behind most crop plants. This study was conducted to clone and characterize cDNA encoding R gene like (RGL) sequences in buffalograss. This report is the first to clone and characterize of buffalograss RGLs. Degenerate primers designed from the conserved motifs of known R genes were used to amplify RGLs and fragments of expected size were isolated and cloned. Sequence analysis of cDNA clones and analysis of putative translation products revealed that most encoded amino acid sequences shared the similar conserved motifs found in the cloned plant disease resistance genes RPS2, MLA6, L6, RPM1, and Xa1. These results indicated diversity of the R gene candidate sequences in buffalograss. Analysis of 5' rapid amplification of cDNA ends (RACE), applied to investigate upstream of RGLs, indicated that regulatory sequences such as TATA box were conserved among the RGLs identified. The cloned RGL in this study will further enhance our knowledge on organization, function, and evolution of R gene family in buffalograss. With the sequences of the primers and sizes of the markers provided, these RGL markers are readily available for use in a genomics-assisted selection in buffalograss. PMID- 17284778 TI - Analysis of the quality of contact-pin fabricated oligonucleotide microarrays. AB - As the quality of microarrays is critical to successful experiments for data consistency and validity, a reliable and convenient quality control method is needed. We describe a systematic quality control method for large-scale genome oligonucleotide arrays. This method is comprised of three steps to assess the quality of printed arrays. The first step involves assessment of the autofluorescence property of DNA. This step is convenient, quick to perform, and allowed reuse of every array. The second step involves hybridization of arrays with Cy3-labeled 9-mer oligonucleotide target to assess the quality and stability of oligonucleotides. Because this step consumed arrays, one or two arrays from each batch were used to complement the quality control data from autofluorescence. The third step involves hybridization of arrays from every batch with transcripts derived from two cell lines to assess data consistency. These hybridizations were able to distinguish two closely related tissue samples by identifying a cluster of 20 genes that were differently expressed in U87MG and T98G glioblastoma cell lines. In addition, we standardized two parameters that significantly enhanced the quality of arrays. We found that longer pin contact time and crosslinking oligonucleotides at 400 mJ/cm(2) were optimal for the highest hybridization intensity. Taken together, these results indicate that the quality of spotted oligonucleotide arrays should be assessed by at least two methods, autofluorescence and 9-mer hybridization before arrays are used for hybridization experiments. PMID- 17284779 TI - Suppression of hyperglycemia in NOD mice after inoculation with recombinant vaccinia viruses. AB - In autoimmune (type 1) diabetes, autoreactive lymphocytes destroy pancreatic beta cells responsible for insulin synthesis. To assess the feasibility of gene therapy for type 1 diabetes, recombinant vaccinia virus (rVV) vectors were constructed expressing pancreatic islet autoantigens proinsulin (INS) and a 55 kDa immunogenic peptide from glutamic acid decarboxylase (GAD), and the immunomodulatory cytokine interleukin (IL)-10. To augment the beneficial effects of recombinant virus therapy, the INS and GAD genes were fused to the C terminus of the cholera toxin B subunit (CTB). Five-week-old non-obese diabetic (NOD) mice were injected once with rVV. Humoral antibody immune responses and hyperglycemia in the infected mice were analyzed. Only 20% of the mice inoculated with rVV expressing the CTB::INS fusion protein developed hyperglycemia, in comparison to 70% of the mice in the uninoculated animal group. Islets from pancreatic tissues isolated from euglycemic mice from this animal group showed no sign of inflammatory lymphocyte invasion. Inoculation with rVV producing CTB::GAD or IL 10 was somewhat less effective in reducing diabetes. Humoral antibody isotypes of hyperglycemic and euglycemic mice from all treated groups possessed similar IgG1/IgG2c antibody titer ratios from 19 to 32 wk after virus inoculation. In comparison with uninoculated mice, 11-wk-old NOD mice injected with virus expressing CTB::INS were delayed in diabetes onset by more than 4 wk. The experimental results demonstrate the feasibility of using rVV expressing CTB::INS fusion protein to generate significant protection and therapy against type 1 diabetes onset and progression. PMID- 17284780 TI - Potential misidentification of cyclooxygenase-2 by Western blot analysis and prevention through the inclusion of appropriate controls. AB - Cyclooxygenase (COX)-2 plays an important role in the development of cancer and has been recognized as a potential therapeutic target. Because nonsteroidal anti inflammatory drugs (NSAIDs) are able to inhibit the activity of this enzyme, the potential efficacy of such drugs for purposes of cancer prevention or therapy is an area of intense research. Therefore, it is of critical importance to unequivocally determine the expression levels of COX-2 protein in tumor cells. In this regard, there are several conflicting reports in the literature where the same type of tumor cell lines were reported as COX-2 positive and as COX-2 negative. We found that during Western blot analysis of COX-2 positive and COX-2 negative cells, different antibodies to COX-2 protein are able to generate strong signals, which are false-positives and can be confused with COX-2. Thus, we believe that some of the conflicting reports on COX-2 expression in tumor cell lines could be the result of improper interpretation of the Western blot signals. Here, we present some of these pitfalls and suggest the inclusion of appropriate controls to unequivocally identify COX-2 protein levels. PMID- 17284783 TI - Tb2Ni2Mg3: a new structure type derived from the Ru3Al2B2 type. PMID- 17284785 TI - Pt2(II) and Pt2(III) dimers containing a Pt2(2,2'-bipyridine)2(mu-N,N dimethylguanidinato)2 unit. PMID- 17284784 TI - The gold(III) tetrachloride salt of L-cocaine. PMID- 17284786 TI - Bis(mu-acetato)(mu-2,6-bis{[(2-hydroxyethyl)(2-pyridylmethyl)amino]methyl}-4 methylphenolato)dinickel(II) hexafluorophosphate hemihydrate. PMID- 17284781 TI - Multiple strategies for gene transfer, expression, knockdown, and chromatin influence in mammalian cell lines and transgenic animals. AB - Manipulation of the eukaryotic genome has contributed to the progress in our knowledge of multicellular organisms but has also ameliorated our experimental strategies. Biological questions can now be addressed with more efficiency and reproducibility. There are new and varied strategies for gene transfer and sequence manipulation with improved methodologies that facilitate the acquisition of results. Cellular systems and transgenic animals have demonstrated their invaluable benefits. In this review, I present an overview of the methods of gene transfer with particular attention to cultured cell lines and large-scale sequence vectors, like artificial chromosomes, with the possibility of their manipulation based on homologous recombination strategies. Alternative strategies of gene transfer, including retroviral vectors, are also described and the applications of such methods are discussed. Finally, several comments are made about the influence of chromatin structure on gene expression. Recent experimental data have shown that for convenient stable transgene expression, the influence of chromatin structure should be seriously taken into account. Novel chromatin regulatory and structural elements are proposed as an alternative for proper and sustained gene expression. These chromatin elements are facing a new era in transgenesis and we are probably beginning a new generation of gene and cancer therapy vectors. PMID- 17284782 TI - Living with heterogeneities in bioreactors: understanding the effects of environmental gradients on cells. AB - The presence of spatial gradients in fundamental culture parameters, such as dissolved gases, pH, concentration of substrates, and shear rate, among others, is an important problem that frequently occurs in large-scale bioreactors. This problem is caused by a deficient mixing that results from limitations inherent to traditional scale-up methods and practical constraints during large-scale bioreactor design and operation. When cultured in a heterogeneous environment, cells are continuously exposed to fluctuating conditions as they travel through the various zones of a bioreactor. Such fluctuations can affect cell metabolism, yields, and quality of the products of interest. In this review, the theoretical analyses that predict the existence of environmental gradients in bioreactors and their experimental confirmation are reviewed. The origins of gradients in common culture parameters and their effects on various organisms of biotechnological importance are discussed. In particular, studies based on the scale-down methodology, a convenient tool for assessing the effect of environmental heterogeneities, are surveyed. PMID- 17284787 TI - (Azido-kappaN)bis(di-2-pyridylamine)copper(II) hexafluorophosphate and (azido kappaN)bis(di-2-pyridylamine)copper(II) chloride tetrahydrate. PMID- 17284788 TI - Hydrogen bonding in dibromo[2-(dimethylaminomethyl)phenyl][2 (dimethylammoniomethyl)phenyl]tin(IV) tetrabromo[2 (dimethylaminomethyl)phenyl]tin(IV). PMID- 17284789 TI - Pentaaquaoxovanadium(IV) bis(trifluoromethanesulfonate). PMID- 17284790 TI - pi-Stacking and hydrogen bonding in catena-poly[[(4,4'-bipyridine kappaN)dioxouranium(VI)]-di-mu-hydroxo]. PMID- 17284791 TI - Poly[mu2-chloro-mu2-1,4-oxathiane-kappa2S:S-copper(I)]. PMID- 17284792 TI - mu-Acetato-1:2kappa2O:O'-diacetato-1kappa2O,O';2kappaO-bis(di-2-pyridylamine) 1kappa2N,N';2kappa2N,N'-isothiocyanato-2kappaN-dicopper(II). PMID- 17284793 TI - Tris(2-methylquinoline-8-selenolato-kappa2N,Se)antimony(III). PMID- 17284794 TI - Poly[[[aqua(2,2'-bipyridine-kappa2N,N')manganese(II)]-mu3-acetylenedicarboxylato kappa3O:O':O''] monohydrate]. PMID- 17284796 TI - A dodecanuclear manganese(II,III) complex of pentaerythritol. PMID- 17284795 TI - (3,8,9,14-Tetraethyl-2,4,13,15 tetramethyltripyrrinato)(trifluoroacetato)palladium(II). PMID- 17284797 TI - Tris(acetylacetonato-kappa(2)O,O')(1,10-phenanthroline-kappa2N,N')erbium(III). PMID- 17284798 TI - (Acetonitrile){2,6-bis[1-(2-ethyl-6 methylphenylimino)ethyl]pyridine}dichlororuthenium(II) dichloromethane hemisolvate: a chain of edge-fused R(6)(6)(24) rings. PMID- 17284799 TI - Five symmetrically substituted 2-aryl-3-benzyl-1,3-thiazolidin-4-ones: supramolecular structures in zero, one and two dimensions. PMID- 17284801 TI - (E)-4-(4-Bromophenyldiazenyl)-2,6-dimethylphenyl acrylate and (E)-2,6-dimethyl-4 (4-methylphenyldiazenyl)phenyl acrylate. PMID- 17284800 TI - Dorzolamide hydrochloride: an antiglaucoma agent. PMID- 17284802 TI - 3-(1-Pyridinio)propanesulfonate and 3-(benzyldimethylammonio)propanesulfonate monohydrate. PMID- 17284803 TI - L-Leucinium perchlorate. PMID- 17284804 TI - Isomorphous brucinium 4-nitrobenzoate methanol solvate and brucinium 4 nitrobenzoate dihydrate. PMID- 17284805 TI - 1-Chloro-2-nitrobenzene: N-O...Cl halogen bonds and aromatic pi-pi stacking, and thermal vibrations in the vicinity of the melting point. PMID- 17284806 TI - 2,4,6-Trimethyl-N-nitroaniline. PMID- 17284807 TI - Bis[3-(trimethylsilyl)propyl] ethylenebisphosphonate, H2DTMSP[EBP]. PMID- 17284808 TI - (Z)-2-(1-Benzyl-5-nitro-1H-indol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-one. PMID- 17284809 TI - 1-(beta-D-Erythrofuranosyl)cytidine (beta-erythrocytidine). PMID- 17284810 TI - Ethyl 4-hydroxy-2,6-diphenyl-5-(phenylsulfanyl)pyridine-3-carboxylate and ethyl 2,6-bis(4-fluorophenyl)-4-hydroxy-5-(4-methylphenylsulfanyl)pyridine-3 carboxylate: supramolecular aggregation through C-H...O, C-H...F and C-H...pi interactions. PMID- 17284811 TI - 9-Methyl-3-phenyldiazenyl-9H-carbazole: X-ray and DFT-calculated structures. PMID- 17284812 TI - Conformation of tert-butoxycarbonylglycyl-dehydroalanyl-glycine methyl ester in the crystalline state and calculated in the gas phase. PMID- 17284813 TI - 2-{[Bis(2-pyridylmethyl)amino]methyl}-6-[(2-hydroxyanilino)methyl]-4 methylphenol: a novel binucleating asymmetric ligand as a precursor to synthetic models for metalloenzymes. PMID- 17284814 TI - 1-[(5-tert-Butyl-2-hydroxyphenyl)iminomethyl]-2-napthol. PMID- 17284815 TI - Cocrystals composed of 4,4'-(fluorene-9,9-diyl)diphenol and 6-methyl-2H-pyridone. PMID- 17284816 TI - 3,4-Di-2-pyridyl-1,2,5-oxadiazole and its perchlorate salt. PMID- 17284817 TI - 2'-Deoxy-2-fluorotubercidin. PMID- 17284818 TI - 1-(6-Amino-1,3-benzodioxol-5-yl)-3-(4-pyridyl)prop-2-en-1-one crystallizes with Z' = 2: hydrogen-bonded supramolecular substructures in one and two dimensions, each containing only one type of molecule. PMID- 17284819 TI - Non-denaturing fluorescence in situ hybridization to find replication origins in a specific genome region on the DNA fiber. AB - Fluorescence in situ hybridization (FISH) is a useful method of determining the replication timing of specific genomic loci in mammals and of delineating replicon structures on DNA fibers in combination with in vivo replication labeling. In the case of simultaneous detection of a FISH probe and replicated forks, however, the DNA fibers are damaged by the DNA denaturation step for FISH detection, and the resulting fragmented fluorescence signals prevent analysis at high resolution. Here we found that hybridization of the probe to the genomic DNA was possible even under non-denaturing condition, but only at the time its genomic region replicated. Using the method designated non-denaturing FISH, we determined the replication timing of a specific BAC clone and the standard clones, and found that at least one replication origin exists within the genomic region covered by its BAC clone as an example. PMID- 17284820 TI - Loss of a GPI-anchored membrane protein Aah3p causes a defect in vacuolar protein sorting in Schizosaccharomyces pombe. AB - Schizosaccharomyces pombe has four alpha-amylase homologs (Aah1p-Aah4p) with a glycosylphosphatidylinositol (GPI) modification site at the C-terminal end. Disruption mutants of aah genes were tested for mislocalization of vacuolar carboxypeptidase Y (CPY), and aah3Delta was found to secrete CPY. The conversion rate from pro- to mature CPY was greatly impaired in aah3Delta, and fluorescence microscopy inidicated that a sorting receptor for CPY, Vps10p, mislocalized to the vacuolar membrane. These results indicate that aah3Delta had a defect in the retrograde transport of Vps10p, and that Aah3p is the first S. pombe specific protein required for vacuolar protein sorting. PMID- 17284821 TI - Characterization of short interspersed elements (SINEs) in a red alga, Porphyra yezoensis. AB - Short interspersed element (SINE)-like sequences referred to as PySN1 and PySN2 were identified in a red alga, Porphyra yezoensis. Both elements contained an internal promoter with motifs (A box and B box) recognized by RNA polymerase III, and target site duplications at both ends. Genomic Southern blot analysis revealed that both elements were widely and abundantly distributed on the genome. 3' and 5' RACE suggested that PySN1 was expressed as a chimera transcript with flanking SINE-unrelated sequences and possessed the poly-A tail at the same position near the 3' end of PySN1. PMID- 17284823 TI - Effect of a hypolipidemic drug, Di (2-ethylhexyl) phthalate, on mRNA-expression associated fatty acid and acetate metabolism in rat tissues. AB - Di (2-ehtylhexyl) phthalate (DEHP) is a peroxisome proliferator and a drug having a hypolipidemic effect. The body-weight change of rats treated with DEHP was lower than that of rats in an untreated control group. Expressions of long-chain acyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase, which are involved in fatty acid oxidation and acetate formation in mitochondria, showed an increase in the liver and testes of rats treated with DEHP. The expression of acetyl-CoA synthetase 1 was significantly decreased in the testes and relatively decreased in the liver, while the expression of acetyl-CoA synthetase 2 was significantly increased in the heart. Furthermore, the expressions of acetyl-CoA carboxylase in heart and testes showed a tendency to decrease. From these results, it is suggested that DEHP-treatment increased fatty acid oxidation and acetate formation in liver and testes, and that acetate utilization was increased in peripheral tissues such as the heart. PMID- 17284822 TI - Pepper beta-galactosidase 1 (PBG1) plays a significant role in fruit ripening in bell pepper (Capsicum annuum). AB - During bell pepper (Capsicum annuum L.) fruit ripening, beta-galactosidase activity increased markedly as compared with other glycosidases. We purified 77.5 kDa exo-1,4-beta-D-galactanase from red bell pepper fruit classified as beta galactosidase II. A marked decrease in galactose content appeared during fruit ripening, especially in the pectic fraction. The purified enzyme hydrolyzed a considerable amount of galactose residues in this fraction. We isolated bell pepper beta-galactosidase (PBG1) cDNA. This PBG1 protein contained the putative active site, G-G-P-[LIVM]-x-Q-x-E-N-E-[FY], belonging to glycosyl hydrolase family 35. Quantitative RT-PCR revealed that the expression of PBG1 in red fruit was significantly stronger than that from any other tissues. Moreover, expression of PBG1 occurred prior to that of pepper endo-polygalacturonase 1 (PPG1), the major fruit-ripening enzyme. Based on these results, it appears that the hydrolysis of galactose residues in pectic substances is the first event in the ripening process in bell pepper fruit. PMID- 17284824 TI - Efficient incorporation of unsaturated fatty acids into volicitin-related compounds in Spodoptera litura (Lepidoptera: Noctuidae). AB - We introduced efficient incorporation of unsaturated fatty acids into volicitin [N-(17-hydroxylinolenoyl)-L-glutamine] and N-linolenoyl-L-glutamine, insect derived elicitors of plant volatiles, in the common cutworms Spodoptera litura by the incubation of larval gut tissues with unsaturated (linolenic, linoleic, and oleic acids) or saturated fatty acids (palmitic and stearic acids) sodium salt, and L-[alpha-(15)N]glutamine. PMID- 17284825 TI - Characterization of a NADH:dichloroindophenol oxidoreductase from Bacillus subtilis. AB - We expressed and purified an azoreductase homolog, YvaB, from Bacillus subtilis. YvaB was found to have NADH:2,6-dichloroindophenol oxidoreductase activity, as well as azoreductase activity. Purified YvaB was active without FMN, unlike Escherichia coli azoreductase. YvaB was most active at pH 7.5 and 40 degrees C, and was stable up to 55 degrees C after incubation for 30 min. Remarkably, it was stable in the presence of Ag(+), and was activated by the addition of non-ionic detergents. Other enzymatic properties of YvaB were also investigated. PMID- 17284826 TI - Expression of a functional sphingomyelinase of Pseudomonas sp. TK4 in mammalian cells. AB - We report here the expression of a bacterial sphingomyelinase in mammalian cells as a functionally active form. A chimeric Pseudomonas sphingomyelinase fused with the lysosomal sorting motif of lysosomal acid phosphatase was sorted to lysosomes in mammalian cells. As expected, the chimeric SMase hydrolyzed sphingomyelin in vivo to produce ceramide, part of which was converted to glucosylceramide. PMID- 17284827 TI - Estimation of luminal mucin content in rats by measurement of O-linked oligosaccharide chains and direct ELISA. AB - Changes in the small intestinal mucin contents in rats were evaluated by two methods, viz., a newly established ELISA and a method based on the measurement of O-linked oligosaccharide chains (OSC) as a mucin marker. Significant correlation was observed between the values of ELISA-derived mucins and OSC. The results confirm the usefulness of measurement of OSC as an alternative method for mucin determination. PMID- 17284828 TI - A new colorimetric method for determining the isomerization activity of sucrose isomerase. AB - A new colorimetric method for determining the isomerization activity of sucrose isomerase was developed. This colorimetric method is based on the enzymatic reactions of invertase and glucose oxidase-peroxidase (GOD-POD). The main scheme for assaying sucrose isomerase activity is to degrade sucrose in the reaction mixture to glucose and fructose by invertase and to detect the concentration of glucose generated using GOD-POD. The concentrations of trehalulose and isomaltulose, reaction products of sucrose isomerase, are calculated from the concentration of glucose. This method allows rapid and accurate determination of the isomerization activity of sucrose isomerase without inhibition by hydrolysis activity. PMID- 17284829 TI - Potencies of phosphine peptide inhibitors of mammalian thimet oligopeptidase and neurolysin on two bacterial pz peptidases. AB - Pz peptidases A and B, from a thermophile Geobacillus collagenovorans MO-1, recognize collagen-specific tripeptide units (Gly-Pro-Xaa). They share similarities in function but extremely low identities in primary sequence with mammalian thimet oligopeptidase (TOP) and neurolysin. Three phosphine peptide inhibitors that selectively inhibit TOP and neurolysin on two bacterial Pz peptidases were investigated. They showed potent inhibition of both Pz peptidases in a range from 10 to 100 nM. PMID- 17284830 TI - An anthocyanin compound in buckwheat sprouts and its contribution to antioxidant capacity. AB - The major anthocyanin compound in buckwheat sprouts was determined to be cyanidin 3-O-rutinoside (C3R), based on HPLC data and MS/MS spectra. Investigation of the content of phenolic compounds in commercial buckwheat sprouts indicated that hypocotyls are abundant in C3R and rutin, whereas all of the detected flavonoids are abundant in cotyledons. The superoxide anion radical-scavenging activities (SOD-like activities) of phenolic compounds in buckwheat sprouts and their contents indicated that rutin, isoorientin, and orientin contributed mainly to the SOD-like activity of the extract from buckwheat sprouts. In contrast, the contribution of C3R was substantially lower than that of flavonoids. PMID- 17284831 TI - Evaluation of the astringency of black tea by a taste sensor system: scope and limitation. AB - Grading the astringency of black tea by a taste sensor system was studied. The black tea samples manufactured in India and Sri Lanka were classified into ten steps on the basis of two standard solutions (0.65 mM and 0.26 mM EGCg aqueous solutions). An organoleptic test demonstrated that the sensor output was correlative to the human gustatory sense. PMID- 17284832 TI - Effect of a sake concentrate on the epidermis of aged mice and confirmation of ethyl alpha-D-glucoside as its active component. AB - Generations of Japanese have appreciated the positive effects that sake can have on skin conditions, and studies have shown that concentrated sake suppressed the epidermal barrier disruption caused by ultraviolet B (UVB) irradiation. We investigated the effect of a topical application of a sake concentrate on the murine epidermis and found that the intercellular lipid content in an aged epidermis was significantly increased. Furthermore, the topical application of ethyl alpha-D-glucoside (alpha-EG), a component of sake, brought about a similar improvement in the levels of intercellular lipids. Following on from this, we confirmed that alpha-EG also significantly increased the content of loricrin protein, an indicator of successful corneocyte differentiation, while reducing the number of corneocyte layers in the aged stratum corneum. These results confirmed alpha-EG as the primary active component of the sake concentrate that had a positive effect on the epidermis. alpha-EG increased the intercellular lipid content, accelerated the differentiation of corneocytes, and reduced the thickness, thus improving the functions of the stratum corneum. PMID- 17284834 TI - Augmentation of antigen-specific antibody production and IL-10 generation with a fraction from Rooibos (Aspalathus linearis) tea. AB - Rooibos tea was extracted with boiling water. The aqueous extract was chromatographed in a Diaion HP20 column eluted stepwise with water, 25%, 50% and 75% (v/v) aqueous methanol, and 100% methanol. The water eluate (fraction A) showed an augmenting effect on anti-ovalbumin (anti-OVA) immunoglobulin M (IgM) production in OVA-stimulated murine splenocytes in vitro. Fraction A also showed a strong augmenting effect on interleukin-10 generation in murine splenocytes. Furthermore, continuous ingestion of fraction A was found to increase the anti OVA IgM level in the sera of OVA-immunized mice. PMID- 17284833 TI - A new method of defense response analysis using a transient expression system in rice protoplasts. AB - We established a new plant defense response assay using a transient expression system in rice protoplasts. The assay system sensitively detected defense induction by flagellin, which had previously been assigned to a specific elicitor. Our assay system provides a rapid and efficient way to dissect rice defense mechanisms. PMID- 17284835 TI - Rhythmic cycle of clathrin-coated pit formation at the trans-golgi network in human MDA-MB-435 cells. AB - We studied the in vivo dynamics of enhanced green fluorescent protein-tagged clathrin light chain a (GFP-CLCa) at the trans-Golgi network (TGN) in MDA-MB-435 cells. The intensity of fluorescence signals of GFP-CLCa periodically increased and decreased at the TGN approximately every 100 s. This suggests that the formation of clathrin-coated pits occurs synchronously and periodically at the TGN. PMID- 17284836 TI - Expression of rice (Oryza sativa L. var. Nipponbare) alpha-galactosidase genes in Escherichia coli and characterization. AB - Two putative alpha-galactosidase genes from rice (Oryza sativa L. var. Nipponbare) belonging to glycoside hydrolase family 27 were cloned and expressed in Escherichia coli. These enzymes showed alpha-galactosidase activity and were purified by Ni Sepharose column chromatography. Two purified recombinant alpha galactosidases (alpha-galactosidase II and III; alpha-Gal II and III) showed a single protein band on SDS-PAGE with molecular mass of 42 kDa. These two enzymes cleaved not only alpha-D-galactosyl residues from the non-reducing end of substrates such as melibiose, raffinose, and stachyose, but also liberated the galactosyl residues attached to the O-6 position of the mannosyl residue at the reducing-ends of mannobiose and mannotriose. In addition, these enzymes clipped the galactosyl residues attached to the inner-mannosyl residues of mannopentaose. Thus, alpha-Gal II catalyzes efficient degalactosylation of galactomannans, such as guar gum and locust bean gum. PMID- 17284838 TI - Detection and determination of glyceraldehyde-derived pyridinium-type advanced glycation end product in streptozotocin-induced diabetic rats. AB - GLAP, glyceraldehyde-derived pyridinium-type advanced glycation end product (AGE), formed by glyceraldehyde-related glycation, was identified in the plasma protein and the tail tendon collagen of streptozotocin (STZ)-induced diabetic rats. It was detected in the plasma protein and the collagen in diabetic rats by LC-MS and LC-MS/MS analysis, but was not detected in normal rats. In addition, GLAP was formed from glyceraldehyde-3-phosphate (GA3P) with lysine as well as glyceraldehyde (GLA) with lysine in vitro. Accordingly, it is suggested that an increase in the GLAP level reflects an increase in the GLA level and the GA3P level. GLAP might be a biomarker for reduced activity of the glyceraldehyde related enzymes in the metabolic diseases such as diabetic complications. PMID- 17284837 TI - Role of cysteine residues in 4-oxalomesaconate hydratase from Pseudomonas ochraceae NGJ1. AB - 4-Oxalomesaconate hydratase from Pseudomonas ochraceae NGJ1 is unstable in the absence of reducing reagents such as dithiothreitol, and strongly inhibited by 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). To study the role of cysteine residues in enzyme catalysis, the eight individual cysteine residues of the enzyme were replaced with serine residues by site-directed mutagenesis. The catalytic properties and chemical modification of wild- and mutant type-enzymes by DTNB showed that (i) none of eight cysteine residues was essential for enzyme catalysis; (ii) the inhibition by DTNB was mostly due to modification of Cys-186; (iii) Cys-96 might be another residue reacting with DTNB, and its modification caused an increase in the K(m)-value for 4-oxalomesaconate; (iv) the other six cysteine residues were inaccessible to DTNB, but susceptible to HgCl(2); and (v) only replacement of Cys-186 remarkably improved the stability of the enzyme in the absence of reducing reagent. PMID- 17284839 TI - Expression and characterization of a sigma-class glutathione S-transferase of the fall webworm, Hyphantria cunea. AB - A cDNA encoding glutathione S-transferase (GST) of the fall webworm, Hyphantria cunea, was cloned by reverse transcriptase-polymerase chain reaction. The resulting clone (hcGST) was sequenced and deduced for amino acid sequence, which revealed 87, 59, and 42% identities to Sigma-class GSTs from Bombyx mori, Manduca sexta, and Blattella germanica respectively. A recombinant hcGST protein (rhcGST) was functionally overexpressed in Escherichia coli cells in a soluble form and purified to homogeneity. rhcGST retained more than 75% of its original GST activity after incubation at pHs 6 to 11. Incubation for 30 min at temperatures below 50 degrees C scarcely affected the activity. rhcGST was able to catalyze the reaction of glutathione with 1-chloro-2,4-dinitrobenzene, a universal substrate for GST, as well as with 4-hydroxynonenal, a product of lipid peroxidation. We also found that as compared to B. mori Sigma-class GST, rhcGST had a higher affinity for fenitrothion, an organophosphorus insecticide. PMID- 17284840 TI - Molecular cloning and functional expression of soybean allene oxide synthases. AB - A plant allene oxide synthase (AOS) reacting with 13S-hydroperoxy-9Z,11E,15Z octadecatrienoic acid (13-HPOT), a lipoxygenase product of alpha-linolenic acid, provides an allene oxide which functions as an intermediate for jasmonic acid (JA) synthesis, making AOS a key enzyme regulating the JA level in plants. Although AOSs in various plants have been investigated, there is only limited information about AOSs in soybean (Glycine max). In this study, we cloned and characterized two soybean AOSs, GmAOS1 and GmAOS2, sharing 95% homology in the predicted amino acid sequences. GmAOS1 and GmAOS2 were composed of 564 and 559 amino acids respectively, with predicted N-terminal chloroplast-targeting signal peptides. Both AOSs expressed in Escherichia coli were selective for 13S hydroperoxides of alpha-linolenic and linoleic acids, suggesting the potential of GmAOS1 and GmAOS2 to contribute to JA synthesis. GmAOS1 and GmAOS2 were expressed in leaves, stems, and roots, suggesting broad distribution in a soybean plant. PMID- 17284841 TI - Mining and polishing of the treasure trove in the bacterial genus streptomyces. AB - The complex morphogenesis of the bacterial genus Streptomyces has made this genus a model prokaryote for study of multicellular differentiation, and its ability to produce a wide variety of secondary metabolites has made it an excellent supplier of biologically active substances, including antibiotics. This review summarizes our study of these two characteristics of Streptomyces, focusing on the A-factor regulatory cascade and work derived from the A-factor study. A microbial hormone, A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone), triggers morphological differentiation and secondary metabolism in Streptomyces griseus. The key steps in the A-factor regulatory cascade, including afsA, encoding the key enzyme for A-factor biosynthesis, arpA, encoding the A-factor receptor, and adpA, encoding a transcriptional activator, are elucidated. The target genes of the regulatory cascade include genes of various functions required for morphological development and secondary metabolite formation. The biosynthesis gene clusters for grixazone and hexahydroxyperylenequinone are examples. The former contains the enzymes for novel benzene ring formation and phenoxazinone formation, and the latter contains enzymes belonging to a type III polyketide synthase and a cytochrome P-450. Enzymes of various catalytic functions in Streptomyces are useful as members of an artificial gene cluster constructed in Escherichia coli for fermentative production of plant-specific flavonoids, including isoflavones and unnatural compounds. PMID- 17284842 TI - Characterization of theanine-forming enzyme from Methylovorus mays no. 9 in respect to utilization of theanine production. AB - For development of theanine production from glutamic acid and ethylamine by coupling yeast sugar fermentation as an ATP-regenerating system, several strains were selected from among about 200 methylamine- and/or methanol-assimilating bacteria depending on the theanine-forming activity of their permeated cells. The amount of theanine formed by the cells of the selected strains was much larger than that by the cells of Escherichia coli AD494 (DE3) expressing Pseudomonas taetrolens Y-30 glutamine synthetase (GS), which has been found to be a usable enzyme for theanine production. A GS-like enzyme responsible for the theanine forming reaction was obtained from an obligate methylotroph isolate, Methylovorus mays No. 9. The enzyme was induced by methylamine in the culture medium. A molecular mass of 410-470 kDa was obtained by gel filtration of the enzyme, and 51 kDa by SDS-PAGE analysis. The enzyme showed high activity toward methylamine rather than ammonia, which indicates that it is similar to known gamma glutamylmethylamide synthetase. The isolated enzyme also had high reactivity to ethylamine in a neutral pH range, and formed theanine from glutamic acid and ethylamine in a reaction mixture containing a yeast sugar fermentation system for ATP-regeneration. PMID- 17284843 TI - Degradation of dimethyl disulfide by pseudomonas fluorescens strain 76. AB - Strain 76, which was able to utilize dimethyl disulfide (DMDS) as a sole sulfur source, was screened from our microbial collection. It was identified as Pseudomonas fluorescens by taxonomical characterization and 16S rDNA sequence analysis. It does not belong to the methylotrophs, because it did not grow on DMDS or other C1 compounds as sole carbon source, and DMDS degradation was not repressed in the presence of glucose, Na(2)SO(4), or nutrient broth. Moreover, it showed high resistance to DMDS by growing in DMDS at concentrations up to 9.04 mM. Based on these findings, strain 76 metabolizes DMDS and has dual physiological roles: sulfur assimilation and degradation. Thus it has advantages as a biological scavenger of DMDS. PMID- 17284845 TI - Isolation of tryptophol as an apoptosis-inducing component of vinegar produced from boiled extract of black soybean in human monoblastic leukemia U937 cells. AB - We isolated a novel apoptosis-inducing component, tryptophol, from vinegar produced from boiled extract of black soybean (black soybean vinegar). Compound-6 purified from an ethyl acetate extract of black soybean vinegar using high performance liquid chromatography (HPLC) induced fragmentation of DNA and the development of apoptotic bodies (characteristic physiological features of apoptosis) in U937 cells. By analysis of chemical structure, this active compound was identified as tryptophol. Tryptophol induced apoptosis involving caspase-8 and -3 activation, followed by cleavage of poly (ADP-ribose) polymerase (PARP), as shown by measurement of enzyme activity and immunoblot analysis. The cell viability of normal lymphocytes separated from human blood was less affected by tryptophol, and fragmentation of DNA was not induced in normal lymphocytes. These results indicate that tryptophol isolated from black soybean vinegar inhibited the proliferation of U937 cells by inducing apoptosis via a pathway involving caspase-8 followed by caspase-3, without affecting normal lymphocytes. PMID- 17284844 TI - Role of the ompT mutation in stimulated decrease in colony-forming ability due to intracellular protein aggregate formation in Escherichia coli strain BL21. AB - Recently we found that the cells of Escherichia coli strain BL21 producing a fusion protein, GST-Sup35NM, show a much more rapid decrease in colony-forming ability in the stationary phase than control cells. In this study, it was found that an extract of the cells producing GST-Sup35NM forms fibrous protein polymers containing GST-Sup35NM. In the course of the study, we realized that strain BL21 carried the ompT mutation. We suspected that the deficiency in OmpT protease was responsible for the observed phenotype. To test this, we introduced the wild-type ompT gene into strain BL21, and found that the transformed cells recovered the wild-type phenotype. We concluded that OmpT protease, though known to localize on the cell surface, is involved in protein quality control within the cell. PMID- 17284846 TI - Sequence analysis of full-length cDNA of sex chromosome-linked novel gene 2d-2F9 in Gallus gallus. AB - We obtained two novel W chromosome-linked chick genes by the use of female-male subtraction macroarrays, one of which, 2d-2F9, (recorded as AB188527 in DDBJ) did not have sufficient length (776 bp) to reveal its real form or characteristics. Hence, we obtained full-length Z-linked and W-linked 2d-2F9 genes of 2596 bp and 2589 bp respectively by the oligo-capping and RACE methods. Sequence analysis of these genes not only revealed that there is a counterpart of the W-linked 2d-2F9 gene on the Z chromosome, but also that there is a low homologous area at 5'-UTR between the W- and Z-kinked genes. Using this information, we designed a set of primers to identify sex and to select clones having the Z and W-linked gene (named 2d-2F9-Z and 2d-2F9-W), and also prepared two sets of primers for RT-PCR. These genes were found to be expressed constitutively and ubiquitously from the early embryo to the hatched chick, and they were assigned to the AAA ATP superfamily. PMID- 17284847 TI - Characterization of circadian-associated pseudo-response regulators: II. The function of PRR5 and its molecular dissection in Arabidopsis thaliana. AB - Together with PRR1/TOC1, PRR5 belongs to the small family of Pseudo-Response Regulators (PRRs), which function as clock components of Arabidopsis thaliana. We employed a set of transgenic lines, each of which was designed to misexpress a truncated form of the PRR5 molecule, together with the original transgenic line (named PRR5-ox) that misexpresses the entire PRR5 polypeptide. The results of genetic analysis suggested that PRR5-ox seedlings showed a phenotype of hypersensitivity to red light during early photomorphogenesis in a manner dependent on red light photoreceptors (PhyA and PhyB), but independent of PRR1/TOC1. The set of newly constructed transgenic lines (named PRR5-N-ox and PRR5-C-ox) were also characterized in terms of circadian-associated phenotypes. The results suggest that the N-terminal pseudo-receiver domain of the PRR5 molecule seems to be dispensable for the misexpressed PRR5 molecule to bring about the phenotype of red light sensitivity. However, PRR5-N-ox plants, misexpressing only the pseudo-receiver domain, showed a phenotype of long period of free-running circadian rhythms of certain clock-controlled genes. Considering these and other results, we discuss the structure and function of PRR5 in the context of current views of the circadian clock in higher plants. PMID- 17284848 TI - Metabolic regulation of floral scent in Petunia axillaris lines: biosynthetic relationship between dihydroconiferyl acetate and iso-eugenol. AB - Aromatic scent-related compounds in flowers were comprehensively analyzed by high performance liquid chromatography (HPLC) based on their absorption spectra to understand regulation of metabolism leading to floral scent diversity in Petunia axillaris lines. An unknown compound occurring at similar levels to scent compounds in some plant lines was identified to be dihydroconiferyl acetate. Based on the structure, dihydroconiferyl acetate is likely to be a biosynthetically closely related compound to aromatic scent compounds, especially iso-eugenol. Similar time-course changes of the concentrations suggest that the metabolism of dihydroconiferyl acetate is underlaid by the similar regulation to aromatic scent compounds. Dihydroconiferyl acetate and iso-eugenol occurred almost exclusively, implying that metabolism of the common precursors to each compound is selectively regulated in these plants. The branching of the biosynthetic pathway into dihydroconiferyl acetate and iso-eugenol is probably one of regulatory steps leading to scent diversity in P. axillaris lines. PMID- 17284850 TI - The formation mechanism by yeast of 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H) furanone in Miso. AB - The mechanism of the formation of 4-hydroxy-2(or 5)-ethyl-5-(or 2)-methyl-3(2H) furanone (HEMF) with yeast under caltivation in a medium containing amino carbonyl reactants of ribose and glycine was investigated using stable isotopes of the corresponding compounds. It was confirmed that the skeleton of the five membered ring and the methyl group of the side chain of HEMF was formed from ribose, and that the ethyl group was derived from the glucose metabolite by yeast. The formation of HEMF was confirmed when acetaldehyde as the glucose metabolite and a cell-free extract from yeast were added to the medium containing amino-carbonyl reactants. These results suggest that the role of yeast in HEMF formation is not only to provide the glucose metabolite, but also in combining the amino-carbonyl reactants with the glucose metabolite. PMID- 17284849 TI - Characterization of Circadian-associated pseudo-response regulators: I. Comparative studies on a series of transgenic lines misexpressing five distinctive PRR Genes in Arabidopsis thaliana. AB - Every member of a small family of Pseudo-Response Regulator (PRR) genes, including Timing of Cab Expression 1 (TOC1 [or PRR1]), are believed to play roles close to the circadian clock in the model higher plant Arabidopsis thaliana. In this study we established a transgenic line that misexpresses (or overexpresses) the PRR7 gene. As compared with wild-type plants, the resulting PRR7 misexpressing plants (designated PRR7-ox) showed characteristic phenotypes as to hallmarked circadian-associated biological events: (i) early flowering in a manner independent of photoperiodicity, (ii) hypersensitive response to red light during early photomorphogenesis, and (iii) altered free-running rhythms with long period of clock-associated genes. Finally, a series of all transgenic lines (PRR1 ox, PRR3-ox, PRR5-ox, PRR7-ox, and PRR9-ox) were characterized comparatively with regard to their clock-associated roles. The results suggested that the five homologous PRR factors play coordinate roles, distinctively from one another, and closely to the circadian clock in higher plants. PMID- 17284851 TI - Diverse sugar-binding specificities of marine invertebrate C-type lectins. AB - The sugar-binding specificities of C-type lectins isolated from marine invertebrates were investigated by frontal affinity chromatography (FAC) using 100 oligosaccharides. The lectins included BRA-2 and BRA-3, multiple lectins from the hemolymph of the acorn barnacle, Megabalanus rosa, and BRL from the acorn barnacle, Balanus rostatus. The diverse sugar-binding specificities of the C-type lectins were determined by FAC analysis. BRA-2 recognized alpha2-6 sialylation but not alpha2-3 sialylation on glycans. On the other hand, BRA-3 showed high affinity for oligosaccharides with alpha-linked non-reducing terminal galactose, but not for sialylated forms, and BRL showed enhanced recognition activity towards Lewis(x) and Lewis(a) epitopes. PMID- 17284852 TI - Mutational analyses of a single-stranded telomeric DNA binding domain of fission yeast pot1: conflict with X-ray crystallographic structure. AB - To understand the telomere regulation mechanism in relation to cell aging and cancer, we examined the single-stranded telomeric DNA binding domain (ssDBD) of fission yeast telomere-binding protein Pot1 by constructing a series of deletion mutants. We found that Pot1(1-182) (amino acids 1-182) stably expressed in Escherichia coli without any degradation retained a stable folded structure and functional telomeric DNA binding activity, indicating that Pot1(1-182) corresponds to ssDBD. We investigated the amino acids of Pot1(1-182) involved in single-stranded telomeric DNA recognition by constructing a series of site directed mutants. Although the previously reported X-ray crystallographic structure suggests that 12 amino acids contact the telomeric DNA, an electrophoretic mobility shift assay and isothermal titration calorimetry analyses of the binding ability of the site-directed mutants indicated that only five amino acids significantly contributed to telomeric DNA recognition. We conclude that the contribution to recognition is quite different in magnitude among the amino acids judged to contact the target by X-ray crystallographic structure. PMID- 17284854 TI - Design of sphingomonad-detecting probes for a DNA array, and its application to investigate the behavior, distribution, and source of Rhizospherous sphingomonas and other sphingomonads inhabiting an acid sulfate soil paddock in Kalimantan, Indonesia. AB - Throughout Central and South Kalimantan, Indonesia, strongly acidic soil (pH 2.1 3.7) is widely distributed, and the local acidic soil-tolerant plants, including local rice varieties, often possess sphingomonads in their rhizosphere and rhizoplane. To investigate the behavior of sphingomonads inhabiting the rhizosphere of such acid-tolerant plants, we designed 13 different DNA array probes (each of 72 mer) specific to a group of sphingomonads, using a hypervariable V6 region of the 16S rRNA gene. This DNA array system was used preliminarily for an analysis of microfloral dynamisms, particularly of sphingomonads, in acidic paddock ecosystems, and the results suggest that the acid-tolerant local rice shares rhizospherous sphingomonads with wild Juncus sp., a predominant weed that thrives in acidic paddocks during the off-season for rice farming. This tentative conclusion supports the bio-rationality of the traditional rice farming system with respect to functional rhizobacteria. PMID- 17284853 TI - Kinetic characterization of the oxidation of esculetin by polyphenol oxidase and peroxidase. AB - Esculetin has been described as an inhibitor of tyrosinase and polyphenol oxidase and, therefore, of melanogenesis. In this work, we demonstrate that esculetin is not an inhibitor but a substrate of mushroom polyphenol oxidase (PPO) and horseradish peroxidase (POD), enzymes which oxidize esculetin, generating its o quinone. Since o-quinones are very unstable, the usual way of determining the enzymatic activity (slope of recordings) is difficult. For this reason, we developed a chronometric method to characterize the kinetics of this substrate, based on measurements of the lag period in the presence of micromolar concentrations of ascorbic acid. The catalytic constant determined was of the same order for both enzymes. However, polyphenol oxidase showed greater affinity (a lower Michaelis constant) than peroxidase for esculetin. The affinity of PPO and POD towards oxygen and hydrogen peroxide was very high, suggesting the possible catalysis of both enzymes in the presence of low physiological concentrations of these oxidizing substrates. Taking into consideration optimum pHs of 4.5 and 7 for POD and PPO respectively, and the acidic pHs of melanosomes, the studies were carried out at pH 4.5 and 7. The in vivo pH might be responsible for the stronger effect of these enzymes on L-tyrosine and L-3,4 dihydroxyphenylanaline (L-DOPA) (towards melanogenesis) and on cumarins such as esculetin towards an alternative oxidative pathway. PMID- 17284855 TI - Citrinolactones A, B and C, and Sclerotinin C, plant growth regulators from Penicillium citrinum. AB - New plant growth regulators, named citrinolactones A (1), B (2) and C (3) and sclerotinin C (4), were isolated from Penicillium citrinum and their structures established by spectroscopic methods including 2D NMR. Compounds 1 and 4 increased root growth in proportion to their concentration from 3 to 300 mg/l. In contrast, 2 completely inhibited root growth at a concentration of 300 mg/l and 3 did not show any effect on root growth in a concentration range of 3-300 mg/l. PMID- 17284856 TI - Isolation and characterization of sporulation-initiation mutation in the Bacillus subtilis prfB gene. AB - A Bacillus subtilis prfB45 mutant grew at 42 degrees C, but its sporulation was severely defective at 37 degrees C. Sporulation-specific induction of kinA, spo0A, and spo0H genes was inhibited in the mutant. The effects of temperature up shift and down-shift on sporulation of the prfB45 mutant was observed at an early stage of sporulation. UGA readthrough frequency at non-permissive temperatures for sporulation was higher in the mutant than in the wild-type strain. Temperature-sensitive sporulation of the prfB45 mutant was suppressed by mutations in rpsL coding for S12 of ribosomes, required for accurate termination of translation. Additionally, spontaneous second-site mutations that suppressed the sporulation phenotype of the prfB45 strain were found in the rpoB gene. These results suggest that accurate termination of translation is required for proper initiation of sporulation. PMID- 17284857 TI - Distribution of tocotrienols in rats fed a rice bran tocotrienol concentrate. AB - To examine the distribution of rice bran tocotrienol (T3), we gave rice bran T3 to rats after considering an acceptable daily intake of vitamin E for humans. Male SD rats (5 weeks of age) were fed for 3 weeks on a commercial diet containing 6.4 mg of vitamin E per 100 g wt and additively received vitamin E or the vehicle (vitamin E-free corn oil) by oral intubation. The animals were randomly divided into 4 groups depending on the type of test diet: control (vehicle), non-T3 (no T3 + 4.3 mg of tocopherol (TOC)/kg body weight (b.w.)/day), low-T3 (0.8 mg T3 + 3.5 mg TOC/kg b.w./day), and high-T3 (3.2 mg T3 + 1.1 mg TOC/kg b.w./day). The control rats and rats in the non-T3, low-T3, and high-T3 groups took 4.3 and 8.6 mg of vitamin E/kg b.w./day, respectively. Rice bran gamma-T3 was significantly distributed to the adipose tissue and increased from 1.1 to 10.2 nmol/g of adipose tissue according to the rice bran T3 intake. PMID- 17284858 TI - Textural evaluation of rice cake by chewing and swallowing measurements on human subjects. AB - The difficulty in masticating and swallowing rice cake was quantified. Healthy subjects ate pieces of rice cake (9 g and 3 g) and a modified product (9 g). We used electromyography to measure the activity of the jaw-closing and -opening muscles during chewing, as well as the suprahyoid muscle activity, laryngeal movement, and sound during swallowing. The smaller the rice cake, the shorter the mastication time, the fewer the number of chews, and the less the jaw-closing muscle activity. A modified rice cake product (9 g) was consumed with less mastication effort than the standard rice cake (9 g) and with the same effort as the standard (3 g). Both the sample amount and texture influenced mastication, although neither factor caused a significant difference in swallowing characteristics. These observations suggest that swallowing was induced when the bolus properties became suitable for swallowing, as healthy subjects could adjust their mastication technique according to the food amount and texture. PMID- 17284859 TI - Highly sensitive quantitative analysis of nicotianamine using LC/ESI-TOF-MS with an internal standard. AB - A highly sensitive quantitative method for analyzing nicotianamine (NA) by liquid chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI TOF-MS) is reported. Fluorenylmethoxycarbonylation of nicotianamine reduced its polarity and enabled its retention in a reversed-phase column. The adoption of N(epsilon)-nicotyllysine (NL) as an internal standard ensured reliable quantification by giving a linear calibration curve drawn between the NA/NL molar ratios of standard solutions injected and the NA/NL area ratios in mass chromatograms. The high sensitivity of this analytical method allowed us to measure the amount of NA. This analytical method has applications to all research concerning NA. PMID- 17284860 TI - Restoration by dietary glutamine of reduced tumor necrosis factor production in a low-protein-diet-fed rat model. AB - Tumor necrosis factor-alpha (TNF) production by peritoneal macrophages and its dietary modification were investigated by using rats fed on a low-protein diet. The rats were given a 20% casein (control) diet or a 3% casein diet for 21 days, and TNF production was measured in activated macrophages of these animals. TNF production was significantly lower in macrophages from rats fed on the low protein diet than that in macrophages from rats fed on the control diet. Oral administration of a cabbage extract, a known modulator of TNF production, to the low-protein-diet-fed rats significantly enhanced TNF production by macrophages. Glutamine supplementation to the low-protein diet significantly enhanced TNF production as well as TNF mRNA expression. These results indicate that the 3% casein-diet-fed rat would be useful as a model for reduced TNF production in protein malnutrition. These results also suggest that glutamine administration restored the reduced TNF production associated with protein malnutrition. PMID- 17284861 TI - Enhanced energy expenditure and fat oxidation in humans with high BMI scores by the ingestion of novel and non-pungent capsaicin analogues (capsinoids). AB - The biochemical and physiological indices were monitored in 44 subjects after 4 week capsinoids (capsaicin analogues with low pungency) intake. The subjects were randomly assigned to 3 groups: CSNs3 (3 mg/kg of capsinoids), CSNs10 (10 mg/kg of capsinoids) and the control (placebo). Measurements were performed in the morning on overnight-fasted subjects. The oxygen consumption (VO(2)), resting energy expenditure (REE) and fat oxidation increased slightly compared to pre administration values without any adverse effects, although the increase was not significant. The increase in fat oxidation was positively and significantly correlated with the body mass index (BMI). A meta-analysis was therefore conducted on a subgroup consisting of subjects with BMI >or= 25 (n=28). As a result, not only VO(2) increased significantly (p<0.05) in the CSNs10 group, but also REE in the CSNs10 group and fat oxidation in the CSNs3 and CSNs10 groups tended to increase (p<0.1). Consequently, a capsinoids intake would be able to enhance the energy expenditure and fat burning in humans, particularly those with high BMI. PMID- 17284862 TI - Actin- and microtubule-targeting bioprobes: their binding sites and inhibitory mechanisms. AB - Actin filaments and microtubules play important biological functions in mammalian cells, such as mitosis, cytokinesis, cell signaling, intracellular transport, and cell motility. Therefore, small molecules that interact with these cytoskeletons are expected to be useful not only as antitumor agents, but also as tools for understanding a wide variety of the cellular functions of cytoskeletons. A large number of compounds have been reported as anti-microtubule or anti-actin agents, but only a few compounds have been clarified as to their binding sites on target molecules and their inhibition mechanisms. Here, I describe our recent research into anti-actin and anti-microtubule natural products. Some inhibitors contain active moieties, such as alpha,beta-unsaturated delta-lactone or allely epoxide, in their structure, and covalently bind to their target molecules. Furthermore, some compounds show new inhibition mechanisms by binding on novel sites in target molecules. PMID- 17284863 TI - Nitrogenous ovipositional deterrents in the leaves of sweet pepper (Capsicum annuum) at the mature stage against the leafminer, Liriomyza trifolii (Burgess). AB - Mature leaves of the sweet pepper, Capsicum annuum, exhibited resistance against the American serpentine leafminer, Liriomyza trifolii (Burgess), Agromyzidae. Based on bioassay-guided fractionation, three compounds, namely 4-aminobutanoic acid, (2S,4R)-4-hydroxy-1-methyl-2-pyrrolidine carboxylic acid and 4-amino-1-beta D-ribofuranosyl-2(1H)-pyrimidinone, were isolated from the leaves of sweet pepper. These compounds had significant oviposition deterrence towards adult flies of L. trifolii from laying their eggs on host plant leaves treated at 3.70, 16.60 and 6.45 microg/cm(2), respectively. PMID- 17284864 TI - Genome-wide expression profile of sake brewing yeast under shaking and static conditions. AB - To identify the genes responsible for characteristics, that are different as between sake brewing yeasts and laboratory yeast strains, we used a DNA microarray to compare the genome-wide gene expression profiles of a sake yeast, Saccharomyces cerevisiae K-9 (kyokai 9), and a laboratory yeast, S. cerevisiae X2180-1A, under shaking and static conditions. The genes overexpressed in K-9 more than in X2180-1A were related to C-metabolism, including the HXT, ATP, and COX genes, ergosterol biosynthesis, ERG genes, and thiamine metabolism, THI genes. These genes may contribute to higher growth rates and fermentation ability and the ethanol tolerance of sake yeast. The genes underexpressed in K-9 more than in X2180-1A were CUP1-1 and CUP1-2, PHO genes, which may explain the low copper tolerance and low acid phosphatase activity of sake yeast. These underexpressed genes agree with the features and the alteration of the genome structure of sake yeast. PMID- 17284865 TI - Calcium from LactoCalcium milk mineral after digestion with pepsin stimulates mineralized bone nodule formation in human osteoblast-like SaOS-2 cells in vitro and may be rendered bioavailable in vivo. AB - Many individuals cannot obtain the optimum calcium requirement from food for a variety of reasons. Therefore, calcium supplements are important sources of dietary calcium. One of the calcium sources commercially available is LactoCalcium (milk minerals) that has 28% calcium, and a 2:1 ratio of calcium to phosphorus. The objectives of this study were (a) to examine whether calcium can be released from LactoCalcium by using digestive enzymes and (b) to determine its biological activity by examining its ability to stimulate bone formation. LactoCalcium was treated in vitro by using simulated gastric and intestinal fluids or porcine gastric, pancreatic and intestinal extracts. Our results indicate the role of enzymes or bile extract in the digestion of the product. We show that, by increasing the concentration of pepsin at a fixed concentration of LactoCalcium (substrate), the percentage of released calcium increased in a dose dependent manner, showing that, at the right enzyme concentration, as much as 100% of the calcium present in LactoCalcium can be made available. The biological activity of the digested calcium was demonstrated by the stimulation of mineralized bone nodules in SaOS-2 cells in a dose-dependent manner. Thus, 1 mM and 3 mM calcium released from LactoCalcium increased the nodule area by 23.17 mm(2) (p<0.0001) and 77.78 mm(2) (p<0.0001), respectively, as compared to a value of 0.99 mm(2) at 0.5 mM calcium from LactoCalcium. These results demonstrate the in vitro bioavailability and bioactivity of calcium from LactoCalcium and serve as a basis for carrying out in vivo analyses to determine the suitability of using LactoCalcium as a source of calcium for individuals at risk of developing osteoporosis. PMID- 17284866 TI - Occupational health services in adaptation to the challenges of global market competition--new needs, new strategies, new partnerships. AB - Occupational health services (OHS) have developed together with other social protection measures in response to the challenges of the Industrial Revolution and associated demographic changes of the 19th century. They were perceived as necessary and often even initiated by industry. Their organization and tasks are defined by tripartite international labor law which is largely reflected in national legislations. Increasing global trade and competition based on new technology, have changed not only occupational hazards, but also resulted in a considerable shift of power from national states to corporate enterprises as visible also from increasing deregulation. The development requires adaptation from both, OHS and enterprises, in the best interest of a healthy and productive workforce, of social and economic stability, and of sustainability. PMID- 17284867 TI - The occupational health field in the cochrane collaboration. AB - It is the aim of the Cochrane Collaboration to gather, summarise and disseminate evidence of health care interventions. Recently, the Occupational Health Field has started to do so for occupational health interventions. In this article we would like to describe the organisation and the methods used by the Field. First, the use of research information to improve the quality of occupational health practice is explained. Next, the process and contents of Cochrane Reviews are described. The pros and cons of Cochrane Reviews are listed and what occupational health practitioners can learn from it. There is a great variety of occupational health interventions that requires flexibility in which research design to use. The Occupational Health Field will enhance our understanding of the effectiveness of occupational health interventions in the coming years. PMID- 17284868 TI - Knowledge infrastructure needed for occupational health. AB - Expertise on work and health topics is the foundation for the added value of occupational health (OH) professionals to the health of the working population. Professionals should therefore practice in accordance with high quality standards and latest evidence. As adequate knowledge management and a supportive knowledge infrastructure is needed, OH professionals can discuss opportunities to strengthen both. Occupational health services ought to offer ICT facilities, stimulate organizational conditions and human resource development to implement evidence-based practice. On national level a portal including a virtual library, tailor-made for occupational health, providing access to high quality websites, abstracts and full text articles and books, is a backbone for further developments. Expert groups on various topics can function as a top reference level for new or complicated questions and issues. As an example of an initiative to foster progress, the Dutch Knowledge Infra Structure program for OH professionals (2004-2006) is introduced. This program included efforts to develop the infrastructure itself and projects to develop concrete tools and instruments. PMID- 17284869 TI - Professional ethics in occupational health--Western European perspectives. AB - In this paper, the foundations of professional ethics in occupational health care is described and discussed. After an introduction reminding of the global developments of world economy, communications and trade and reference to cultural and social developments, reference is given the four basic ethical criteria of biomedical ethics of beneficence ("doing good"), non-malfeasance (avoidance of harm), autonomy (integrity) and Justice/Equity-The "Appletown consensus" of 1989. These criteria provide the basis for current thinking and practice in health professions of Western Europe. The principles of ethical analysis, as currently practiced is described using a practical case scenario drawn from experience of challenging tasks for Occupational Health Services in Western Europe. Specific challenges to professional ethics are discussed-the growth of knowledge in subjects and academic disciplines relevant to occupational health and the multiple loyalties of occupational health professionals. The principles of ethical codes and their implementation are touched on. In conclusion, the universality of professional ethical principles of bioethics-including occupational health-is discussed in observing global inter-cultural commonalities and convergence on ethical criteria of central importance. Emphatic recommendation is given to continue inter-cultural exchanges with a view to improve understanding of impact of contextual and cultural factors on ethics in professional occupational health practice. PMID- 17284870 TI - Evidence-based practice guidelines in OHS: are they agree-able? AB - The purpose of this study was to evaluate the acceptance, validity, reliability and feasibility of the AGREE (Appraisal of Guidelines and REsearch and Evaluation) instrument to assess the quality of evidence-based practice guidelines for occupational physicians. In total, 6 practice guidelines of the Netherlands Society of Occupational Medicine (NVAB) were appraised by 20 occupational health professionals and experts in guideline development or implementation. Although appraisers often disagreed on individual item scores, the internal consistency and interrater reliability for most domains was sufficient. The AGREE criteria were in general considered relevant and no major suggestions for additional items for use in the context of occupational health were brought up. The domain scores for the individual guidelines show a wide variety: 'applicability' had on average the lowest mean score (53%) while 'scope and purpose' had the highest one (87%). Low scores indicate where improvements are possible and necessary, e.g. by providing more information about the development. Key experts in occupational health report that AGREE is a relevant and easy to use instrument to evaluate quality aspects and the included criteria provide a good framework to develop or update evidence-based practice guidelines in the field of occupational health. PMID- 17284871 TI - Cost-benefit analysis of a worksite oral-health promotion program. AB - This study was conducted to examine whether oral-health promotion programs provided as an occupational health service for employees were cost-beneficial for employers. The subjects were composed of 357 male workers (20-59 yr of age) who participated in oral-health promotion programs conducted at their workplaces between 1992 and 1997. The design of this study was a quasi-experimental study design in which the three programs (light: 1 visit; medium: 2-4 visits; and heavy: 5-6 visits) were compared through cost-benefit analysis conducted from the viewpoint of the employers. The programs consisted of oral-health checkups by dentists and oral-health education, including that on the proper brushing method, by dental hygienists. The costs of the program included direct costs for the payment of oral-health-care staff and for teaching materials, and indirect costs for the time for employee participation in the program (20 min/employee per visit). The accumulated dental expenses for the seven years were used to calculate benefits, which were determined, based on the differences between 0 visits and each program. The benefit/cost ratios of the three programs were 2.45, 1.46, and 0.73, respectively. These results suggest that a worksite oral health promotion program of medium frequency is cost-beneficial for employers. PMID- 17284872 TI - Managing work-related psychological complaints by general practitioners, in coordination with occupational physicians: a pilot study. AB - Increasingly, workers have psychological work-related complaints, endangering their work ability and causing considerable economic losses. Many employees consult their general practitioner (GP). He, however, often pays insufficient attention to work-relatedness or to coordination with occupational physicians (OPs). Appropriate guidelines are missing. Consequently, we developed a GP guideline to handle these problems in coordination with OPs, and tested it in a pilot, using an explorative, evaluative study design. 23 GPs were trained to include employed patients and to test the guideline. Patients received questionnaires after 0, 4, 10 and 30 wk, GPs after 4 and 30 wk. The result was a new guideline, regarding problem orientation, diagnosis and advice, meant to avoid contradictory GP-OP advice and to activate patient responsibility. It included a GP-OP-patient communication form concerning information exchange and harmonization of insight/advice. Implementing GPs concluded that the guideline promotes recovery and work resumption and OP-GP contact benefits patients, prevents conflicting advice and promotes agreement on task division. They judged guideline efficiency and OP commitment less positively. Patients were positive, especially about GP-OP contact. Accordingly, an improved guideline, when tested for its effectiveness in a Randomized Controlled Trial, can help GPs to cope with a growing, complex problem, in collaboration with their occupational colleagues. PMID- 17284873 TI - Job stressors and job stress among teachers engaged in nursing activity. AB - Teachers and staff members engaged in nursing activity experience more stress than other workers. However, it is unknown whether teachers engaged in nursing activity in schools for handicapped children experience even greater stress. This study evaluated job stressors and job stress among such teachers using a cross sectional study design. The subjects were all 1,461 teachers from all 19 prefectural schools for handicapped children in Shizuoka Prefecture, Japan. We used a brief job stress questionnaire for the survey and 831 teachers completed the questionnaire. Job stressors among teachers engaged in nursing activity were compared with those among teachers not engaged in nursing activity. Job stress among such teachers was estimated by the score for total health risk, and was compared with the score in the Japanese general population. Male and female teachers engaged in nursing activity had a significantly higher level of job stressors for physical work load and job control compared with those not engaged in nursing activity. The scores for total health risk among male and female teachers engaged in nursing activity were 102 points and 98 points, respectively. These scores were not markedly above 100 points which is the mean score in the Japanese general population. PMID- 17284874 TI - Effect of lifestyle modification program implemented in the community on workers' job satisfaction. AB - It is important for occupational health to justify the impact of health promotion programs on job satisfaction, which is associated with work-related outcomes. The aim of this study is to estimate the effects of lifestyle modification activity implemented by the community on job satisfaction, and to analyze the factors which contributed to the improvement of workers' job satisfaction. A lifestyle modification program consisting of aerobic exercise and diet counseling was conducted for 12 wk in the community. Data on 264 workers were obtained before and after the intervention. The subjects were asked to fill out questionnaires about work-related items, lifestyle, and mental health status. In addition to the ameliorations of GHQ, lifestyle, subjective complaints, and the risk factors of lifestyle-related diseases, an improvement in workers' job satisfaction was shown by the participation in the community-based lifestyle modification program. For analyzing factors which contributed to the improvement in job satisfaction, logistic regression analysis was employed. Refreshment from fatigue by sleep independently contributed to the improvement of job satisfaction even after adjusting for the other variables. The health promotion program implemented in the community may be useful for workers' job satisfaction especially through the dissipation of fatigue by refreshment sleep. PMID- 17284875 TI - Relationship between lifestyle and change of cardiovascular risk factors based on a five-year follow-up of employees in Japan. AB - The purpose of this study is to determine the relationship between lifestyle and change of cardiovascular risk factors based on a five-year follow up. The subjects were 307 employees participating in annual health check-ups in Tokyo, Japan from 1998 to 2003. Personal health check-up data were collected on their systolic/diastolic blood pressure (SBP/DBP), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), fasting serum glucose (FSG), uric acid (UA), body mass index (BMI), questionnaire on medication history and Breslow's lifestyle. Over five years, cardiovascular risk factors such as SBP/DBP, TC, TG, FBG, UA and BMI have become worse; however, some of these risk factors were significantly different after 5 yr among lifestyle groups. TG in the poor lifestyle group was significantly higher than in good or moderate lifestyle groups after adjusting for age in men. In women, SBP and BMI in poor lifestyle group were significantly higher than those in good or moderate lifestyle groups after adjusting for age and baseline values. These results show that aging is the major influencing factor of cardiovascular risk factor deterioration. At the same time, lifestyle conditions are related to changes in some cardiovascular risk factors among Japanese employees. PMID- 17284876 TI - Development and process evaluation of the participatory and action-oriented empowerment model facilitated by occupational health nurses for workplace health promotion in small and medium-sized enterprises. AB - The objective of this study is to develop an available empowerment model for workplace health promotion (WHP) in small and medium-sized enterprises (SMEs) and to evaluate its applicability and feasibility. Semi-structured interviews with employers and workers in SMEs were conducted to assess their actual requirements for support. The structure of our new empowerment model was discussed and established through several rounds of focus group meetings with occupational safety and health researchers and practitioners on the basis of results of our interviews. We developed a new participatory and action-oriented empowerment model based on needs for support of employers and workers in SMEs. This new model consists of three originally developed tools: an action checklist, an information guidebook, and a book of good practices. As the facilitators, occupational health nurses (OHNs) from health insurance associations were trained to empower employers and workers using these tools. Approximately 80 SMEs (with less than 300 employees) were invited to participate in the model project. With these tools and continued empowerment by OHNs, employers and workers were able to smoothly work on WHP. This newly developed participatory and action-oriented empowerment model that was facilitated by trained OHNs appears to be both applicable and feasible for WHP in SMEs in Japan. PMID- 17284877 TI - Occupational health nurses' activity after general health examination for workers. AB - In this study, the present condition of occupational health nurse's role after performing general health examination was surveyed. Questionnaires were mailed to 41 companies, and returned questionnaires from 24 of them were analyzed. Although general health examination results were reported to all workers individually in 100% of companies, physician's opinion regarding the examination results were obtained in 86% of companies with part-time physicians comparing with 100% of those with full-time physicians. Health care support related to the examination results were performed by 90% of occupational health nurses and 70% of physicians in companies which employed full-time physicians, but by 100% of occupational health nurses and 50% of physicians in those which employed part-time physicians. In companies with part-time physicians, 64% of occupational health nurses played roles in submitting reports to Labor Standard Inspection Office, but only 30% of occupational health nurses did it in those with full-time physicians. These results show that occupational health nurses working in companies with part-time occupational health physicians were more active in providing health care for workers after general health examination than occupational health nurses working in those with full-time occupational health physicians. PMID- 17284878 TI - Effectiveness of CT for clinical stratification of occupational lung edema. AB - We treated two occupational lung diseases in different situations during military training. The purpose of this study is to investigate the availability of CT scanning for the evaluation of inhalation pulmonary edema. Two soldiers suffered severe lung edema after using a spray for the daily maintenance of their firearms. Four soldiers suffered severe dyspnea after undertaking drills in a narrow zone where numerous smoke bombs had been used. We evaluated these patients from several aspects. CT scans of the chest of spray-induced patients revealed bilateral infiltration predominantly in the upper lung fields. The patients received steroid pulse treatment and gradually recovered. CT scans of the chest of smoke-induced patients revealed bilateral ground-glass attenuation with peripheral lung sparing. The patients gradually recovered with steroid therapy. In accordance with previous studies, CT scans of the chest in our patients demonstrated that the periphery of the lungs remained normal, except in cases of serious injury. When differential diagnosis is required, we consider that CT scans of the chest are particularly useful; CT findings are useful in determining the severity of lung injury as well as the diagnosis of inhalation pulmonary edema. PMID- 17284879 TI - Heat stress standard for hot work environments in Japan. AB - Threshold limit values (TLVs) are intended to protect workers from the severest effects of thermal stress and to establish the exposures to heat in working conditions. Earlier, acute heat strokes often occurred as a result of working in hot environments in Japan. However, acute heat strokes recently sometimes occurred in outdoor work environments such as industrial constructions and agriculture. Seasonal variations in weather are significant and the climatic conditions vary. The criteria are mainly set for working in mines, factories, and so on. WBGT is a useful evaluation index for hot environments; however, it is not commonly used for work practices. WBGT could be calculated and should be commonly used as a standard during summer. Japan mainly has a very hot and humid climate during summer. With regard to the thermal standard for offices, humidity also creates a problem in the indoor thermal conditions. Therefore, it is better to decide the TLVs of the thermal conditions according to seasons and activity levels. Inadequate thermal stress may cause discomfort and adversely affect the performance, safety, and harm to health. Further, thermal factors in the work environment must be measured and evaluated under light workload conditions like desk work for safety and work efficiency. PMID- 17284880 TI - Comparison of subjective symptoms and hot prevention measures in summer between traffic control workers and construction workers in Japan. AB - In the present study, a survey on subjective symptoms and hot prevention measures in summer was conducted in 204 male traffic control workers and 115 male construction workers. Work loads of traffic control workers and construction workers were estimated at RMR 1-2 and RMR 2-4, respectively. A self-administered questionnaire was used to collect information on age, occupational career, working habit, present or past history of diseases, individual preventive measures to the heat, and subjective symptoms in the summer. Daily working hours in the sunshine of the traffic control workers were significantly longer than those of the construction workers. Prevalence rates of changing clothes frequently, avoiding direct exposure of face and neck to sunlight using towel like materials, and wearing sunglasses in the traffic control workers were significantly lower than the construction workers. Prevalence rates of symptoms in the upper extremities in the traffic control workers were significantly lower than those in the construction workers. Prevalence of work difficulty due to hot weather during work in the traffic control workers was significantly lower than the construction workers. On the basis of the results obtained, some preventive countermeasures to improve working environment are presented. PMID- 17284881 TI - Heat exposure control using non-refrigerated water in Brazilian steel factory workers. AB - To test an economically reasonable method to reduce thermal stress, we performed an alternated intervention-control study on 2 groups of 8 male steel workers performing the same jobs, using 2 l of water at ambient temperature (23.5 degrees C +/- 1.4), poured on the head and hands. Each group participated for 2 d as control and 2 d as intervention during 4 consecutive summer days in Brazil, 5 h per shift per day. Testing was done by: 1) recording of temperature by thermistors placed on the external ear canal through earplug, skin (chest, upper arm, inner thigh, outer calf) and clothes; 2) recording of heart rate; and 3) Wet Bulb Globe Temperature recording. The intervention was held hourly, when body weight and water intake were evaluated. Symptoms and subjective sensations were evaluated in the beginning and at the end of each shift. No differences were observed in external ear canal and skin temperatures. Subjective thermal sensation (p = 0.018), sweat perception (p = 0.043), and tiredness (p = 0.028) presented positive statistically significant results when comparing intervention to control measurements. In conclusion, our results could not provide evidence that the proposed method cools the analyzed temperatures, although the subjective evaluation suggests a decrease in the head skin temperature, which could be a useful comfort measure. PMID- 17284882 TI - Thermal limits of men in moderate to heavy work in tropical farming. AB - The farmers in tropical climate are exposed to high heat during the summer months. The study examined the physiological strains of farmers (N=26) to six combined exposures of work and high heat, with moderate and heavy work (26 to 50%, and 51 to 75% VO(2max)) and three ambient conditions, i.e., 34.4 to 42.2 degrees C WBGT (inside) in an environmental chamber. While the cardio-respiratory responses and Tcr were predominantly influenced by the work severity (p<0.001), the environmental warmth greatly influenced the sweating response (p<0.001). The importance was placed on the segmental Tsk as the first rank indicator of the bodily heat strain. Both the environmental warmth and work severity had independent discernable effects on the dynamic equilibrium of the central and peripheral mechanism to regulate the body temperature. The segmental and compartmental (core, muscle, fat and skin) heat balance analysis indicated the span of convergence of the segmental core and muscle temperatures to the divergence of skin and fat temperatures (CORE-SHELL) as a quantitative estimate of the segmental gradient for heat transfer. The summation of heat exchange across the compartments and segments yielded the transient change in Tcr (0.06 to 0.12 degrees C/min), with significant difference between the moderate and heavy work. The Tcr of 39 degrees C was taken as the limit of tolerance for the farmers, and by defining the criteria limit of Tcr of approximately 2.5 degrees C gradient from the basal Tcr and the rate of change in Tcr, the tolerance times were estimated. Corollary to the development of ISO 7933 standard (PHS index), the predictions of tolerance times from the transient change in Tcr or the exponential relationship with the WBGT (tolerance time, min = 1,841 e (-0.103 WBGT)) were useful to suggest the protective limit for men at work in extremely hot environment. The simplicity of prediction lies in using WBGT as a criterion. The exponential equation estimated the tolerance time of 55 min at 34 degrees C WBGT, and up to 38 degrees C WBGT, the decrease in tolerance time was 4 to 5 min per degree increase in environmental warmth. Beyond 38 degrees C WBGT, the estimated tolerance time decreased by 2 to 3 min per degree increase in WBGT. Further optimization and validation of the knowledge for men and women farmers in different age groups will have application in managing heat illnesses and disorders in tropical farming. PMID- 17284883 TI - Prediction computer program for whole body temperatures and its application under various working level and thermal environmental condition combinations. AB - We introduced a computer program developed for the numerical analysis of thermal conditions of all segments and blood circulatory systems in the human body to precisely evaluate human thermal physiological responses. In this program, a cylindrical model consisting of internal multi-layers is adapted for the segment of the human body. For the multi-layered concentric cylindrical model we adopted a new numerical solution method. By using this computer program the internal tissue temperatures, heat fluxes and blood temperatures of all segments in the human body could be calculated simultaneously. This program also included a subroutine for calculation of thermoregulatory response. This paper describes the improvements made to this computer program for simulating individual physical differences and its application to various working levels. The main points for improvement were the assigning procedures of physical characteristics of individuals and local muscle heat production. The improved computer program was used to simulate the whole body temperatures of the subjects during exercise described in Gagge, Stolwijk and Saltin (1969) were simulated. The calculated results were agreed with the measured results under the combination of the three kinds of exercise and the three types of environmental condition. PMID- 17284884 TI - Extended work periods. AB - A literature review of 105 studies on the effects of extended daily working hours was conducted. Potential negative effects of extended working hours are discussed: More accidents on the job; more accidents off the job; reduced duration and quality of sleep due to moonlighting; sleepiness; reduced alertness; fatigue; adverse effects on performance; prolonged toxic exposure; adverse effects on health; increased absenteeism; problems communicating with managers; and problems while driving home. Potential positive effects of extended working hours are discussed: Less travel time and costs; more time for the family, social life, and domestic duties; increased satisfaction with working hours; fewer handovers; and less overtime. No firm conclusions can be drawn because of the partly contradictory results and the methodological problems of many studies. However, caution is advised when considering the introduction of extended work shifts, particularly where public safety is at stake. A checklist is provided (concerning work load, breaks, staffing level, systematic assessments of health and safety factors) to support decisions for or against the use of extended work shifts. PMID- 17284885 TI - Ultraviolet action spectrum for cell killing in a human lens epithelial cell line. AB - There are many sources of ultraviolet (UV) radiation in the workplace. Action spectrum data are necessary for establishing methods to evaluate UV hazards. We determined a UV action spectrum for cell killing in the human lens epithelial cell line SRA 01/04 by measuring the viability of cells exposed to UV at 8 different wavelengths ranging from 259.5 to 300.5 nm in a carefully designed and controlled experiment. The action spectrum based on LD50 is nearly flat or falls slightly with wavelength in the short-wavelength region and then rises increasingly steeply at longer wavelengths. UV at 267.5 nm is most effective in cell killing, with an LD50 of 8.86 Jm(-2). The action spectrum for killing lens epithelial cells in humans (in vivo action spectrum) derived from the present results falls monotonically with wavelength in the range studied, suggesting that UV at wavelengths longer than 300.5 nm may also be highly effective in killing lens epithelial cells in humans and, therefore, in causing cataract. Further studies should be conducted with UV at longer wavelengths. PMID- 17284886 TI - Benzyl alcohol as a marker of occupational exposure to toluene. AB - Benzyl alcohol (BeOH) is a urinary metabolite of toluene, which has been seldom evaluated for biological monitoring of exposure to this popular solvent. The present study was initiated to develop a practical method for determination of BeOH in urine and to examine if this metabolite can be applied as a marker of occupational exposure to toluene. A practical gas-liquid chromatographic method was successfully developed in the present study with sensitivity low enough for the application (the limit of detection; 5 microg BeOH /l urine with CV=2.7%). Linearity was confirmed up to 10 mg BeOH/l, the highest concentration tested, and the reproducibility was also satisfactory with a coefficient of variation of 2.7% (n=10). A tentative application of the method in a small scale study with 45 male workers [exposed to toluene up to 130 ppm as an 8-h time-weighted average (8-h TWA)] showed that BeOH in the end-of-shift urine samples was proportional to the intensity of exposure to toluene. The calculated regression equation was Y=50+1.7X (r=0.80, p<0.01), where X was toluene in air (in ppm as 8-h TWA) and Y was BeOH in urine (in microg/l of end-of-shift urine). The levels of BeOH in the urine of the non-exposed was about 50 microg/l, and ingestion of benzoate as a preservative in soft drinks did not affect the BeOH level in urine. The findings as a whole suggest that BeOH is a promising candidate for biological monitoring of occupational exposure to toluene. PMID- 17284888 TI - Five-hour sleep restriction for 7 days increases subjective sleepiness. AB - We investigated the effects of a 5-h sleep restriction for 7 d on subjective sleepiness in an ambulatory condition by comparing them with baseline conditions consisting of an 8-h sleep for 7 consecutive days. Subjects were 13 healthy male students (mean age 21.1 yr). Each subject was required to get 8 h of sleep (baseline, from 2300 to 0700) for 7 d, and 5 h of sleep (sleep restriction, from 0100 to 0600) for 7 d in an ambulatory condition. The order of the two sleep schedules was randomly assigned. Subjective sleepiness was assessed by a Visual Analog Scale (VAS) every 3 h at 0900, 1200, 1500, 1800, and 2100 for 7 successive days during each sleep schedule. The VAS score during sleep restriction gradually increased up to the 5th day and then reached a plateau. The patterns of time course changes in the VAS score were similar to those at baseline. The VAS scores showed a peak at 0900, taking a dip at 1200, and then gradually increasing toward 2100. The mean VAS score of the last three days of the 5-h sleep restriction was significantly higher than that at baseline (p<0.001). A 5-h sleep restriction for 7 d in an ambulatory condition increased subjective sleepiness up to the 5th day and then reached a plateau. The patterns of the time-course changes in sleepiness of 5-h sleep restriction per day did not differ from that at baseline. PMID- 17284887 TI - Health promoting behaviors and factors related to lifestyle among Turkish workers and occupational health nurses' responsibilities in their health promoting activities. AB - The purposes of this study were to describe health-promotion lifestyle profile of 264 Turkish workers, to determine the factors which affect their lifestyle and to describe occupational health nurses' responsibilities in their health promoting activities to compare their profile with those published from other studies using Health-Promoting Lifestyle Profile. This is a descriptive study. Study was conducted in a food industry. 530 workers are working in this workplace. Approximately fifty percent of the workers participated in this study. The convenience sample composed of 264 workers. Data were collected using a questionnaire about socio-demographic features developed by the investigators and Health Promoting Lifestyle Profile developed by Walker et al. Subscales with the highest means in this study were interpersonal support and self-actualization. Compared to workers reported from other studies, Turkish workers got low scores of self-actualization, nutrition, interpersonal support and stress management. There was no statistically significant difference between total scores and gender, marital status and education. However, there was a statistically significant difference between age and exercise and nutrition. Moreover, as income increased, so did health promoting behaviors. There was a statistically significant difference between perceived health status and importance placed on health and overall health promoting life style and each health promoting behavior. It is important that occupational health nurses identify health behaviors, perceived health status and cultural aspects likely to affect health behaviors among workers. Thus, they may develop effective tools to protect and promote workers' health. PMID- 17284889 TI - Physiological and subjective assessment of food grain handling workers in West Godavari district, India. AB - There are many rice mills and food grain depots where a large number of workers are engaged for processing paddy and rice, storage and distribution. Lifting, carrying and depositing sacs of food grain are the major jobs carried out by these workers. The present study was undertaken to evaluate the workers with respect to their nutritional status, workload, energy expenditure and musculoskeletal pain or discomfort resulting out of work practice. Average peak heart rate of the depot and rice mill workers suggested the workload as moderate to very heavy. Their average energy expenditure values also indicated the workload as moderate to heavy. Subjective assessment of the workers showed the workload as heavy for 60.7% depot workers and 23.1% rice mill workers. Musculoskeletal pain or discomfort was maximally reported in knee by 59% depot workers whereas low back and knee was reported by 61.5% rice mill workers. Besides the weight of the sac, awkward postures like bending and twisting of trunk adopted frequently causes the problem. Further studies and rationalization of work method may improve the health and safety of the workers. PMID- 17284890 TI - Plasma 17-alpha-OH-progesterone in male workers exposed to traffic pollutants. AB - The aim of the study is to evaluate if the occupational exposure to urban pollutants could cause alterations on 17-alfa-hydroxy-progesterone plasma levels and related diseases in male traffic policemen. 17-alpha-OH-P is synthesized in Leydig cells and in adrenals; it influences spermiogenesis, acrosoma reaction, testosterone biosynthesis, blocking of gonadotropin secretion; it regulates learning, memory and sleep. After excluding principal confounding factors, i.e., rotating or night shifts, exposure to solvents, paints and pesticides during time off and smoking, traffic policemen were matched with controls by age, working life and drinking habit. Finally, 112 traffic policemen and 112 controls were included in the study. In traffic policemen 17-alpha-OH-P mean values were significantly higher vs. controls. The distribution of 17-alpha-OH-P values in both groups was significant. An increased frequency of fertility disorders referred to the questionnaire items were found in traffic policemen vs. controls, but the difference was not significant. The occupational exposure to low doses of chemical urban stressor, interacting with and adding to the psychosocial ones, could alter plasma 17-alpha-OH-P concentrations in traffic policemen vs. controls. 17-alpha-OH-P could be used as an early biological marker, even before the onset of the reproductive and mental health diseases. PMID- 17284892 TI - Associations of depressive symptoms with regular leisure activity and family social support among Japanese workers. AB - This study was performed to determine the associations of depressive symptoms with regular leisure activity and family social support among Japanese workers. The study participants consisted of 1,605 men and 348 women. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression scale. Multiple logistic regression analysis was used to adjust for potentially associated variables. Depressive symptoms were associated with lack of regular leisure activity for men [odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.55-2.71] and for women (OR = 2.53, 95% CI = 1.30-4.95). Depressive symptoms were also associated with lack of family social support for men (OR = 1.87, 95% CI = 1.43-2.43). Although a cross-sectional study does not determine which factors are determinants or consequences, these findings suggest regular leisure activity for men and women and family social support for men are independently associated with depressive symptoms. PMID- 17284891 TI - A correlation between increases in suicide rates and increases in male unemployment rates in Mie prefecture, Japan. AB - The number of suicides in Japan has increased from approximately 22,000 per year in 1988-1997 to over 30,000 per year since then. It has also increased in Mie prefecture during that period. In the present study, we investigated the correlation between annual suicide rates in Mie prefecture, Japan from 1996-2002 and the annual unemployment rate in Japan from 1996-2002 among males. Among the results, annual suicide rates in total correlated with the unemployment rate in Japan, but the relation was not statistically significant: r(7)=0.76, r(2)(7)=0.58, p=0.05 (y=3.54x+6.37); the rates in males, however, correlated significantly with the unemployment rate in Japan: r(7)=0.85, r(2)(7)=0.73, p=0.01 (y=5.72x+4.49). In addition, we found that annual suicide rates in total correlated significantly with the male unemployment rates. When a patient is unemployed and in a bad situation, the medical staff and the family should be aware of the correspondence between suicide rates and unemployment. PMID- 17284893 TI - Paraesophageal hiatal hernia-induced dyspnea. PMID- 17284894 TI - Dextromethorphan premedication reduces midazolam requirement: objective and subjective parameters in peribronchoscopy. AB - BACKGROUND: Coughing is increased during bronchoscopy and may last for several hours after the procedure. Also prior to the procedure patients show high levels of anxiety due to fear of the pain and breathing difficulties that they might experience during the procedure. OBJECTIVES: To evaluate the antitussive, anxiolytic and sedative effect of dextromethorphan (DM) premedication on the amount of intravenous midazolam during bronchoscopic procedures. METHODS: Sixty consecutive patients undergoing scheduled bronchoscopy were randomly allocated in a double-blind, placebo-controlled study. Half received 90 mg DM and half placebo. Local anesthesia with 2 ml of repeated intratracheal instillation of 1% lidocaine as needed during bronchoscopy was applied. Midazolam 1 mg (maximum of 5 mg) was administered intravenously until a satisfactory sedation was achieved. RESULTS: Heart rate, systolic and diastolic pressure and SpO(2) were assessed before and during bronchoscopy. A visual analog score (VAS) for pain, cough, communication, cooperation, emotional state, complaints, expectoration, level of information about the procedure, feeling of unpleasantness and stress level assessed before and after the examination by the patient and the physician was used. There were no significant differences in the reported degrees of difficulty in undergoing bronchoscopic procedures. DM patients needed significantly fewer lidocaine instillations and lower midazolam dosage, achieved better analgesia, had lower emotion and complaint scores, significantly less coughing, significantly less stress, were significantly more cooperative, found that the procedure was much less unpleasant than they had expected, and produced less sputum at end of the procedure. CONCLUSIONS: DM is an effective bronchoscopic premedication in combination with midazolam and improves the overall well-being of the patients. PMID- 17284895 TI - Evaluation of peritoneal transport and membrane status in peritoneal dialysis: focus on incident fast transporters. AB - BACKGROUND/AIM: The determinants of baseline fast solute transport are still unclear. We prospectively investigated the relationship of peritoneal solute transport with markers of inflammation, angiogenesis, and membrane status, with a focus on fast transporters. METHODS: Seventy-one incident peritoneal dialysis patients were assessed with baseline and annual peritoneal equilibration tests, using a 3.86% glucose dialysis solution. Residual renal function and markers of inflammation, including systemic and intraperitoneal interleukin-6 (IL-6), effluent cancer antigen 125 (CA-125), and vascular endothelial growth factor (VEGF) appearance rates (ARs), were investigated. The time course of the dialysate-to-plasma ratio of creatinine (D/P creatinine ratio) and its relationship with the biomarkers were investigated by a mixed linear model. RESULTS: Incident fast/fast average transporters had a similar age, diabetes prevalence, and serum and effluent IL-6 levels, but significantly higher levels of CA-125 and VEGF ARs than the slow/slow average group; the D/P creatinine ratio was not correlated with systemic IL-6, but was correlated with effluent CA-125 AR (r = 0.45, p < 0.0001) and VEGF AR (r = 0.52, p < 0.0001). The D/P creatinine ratio decreased with a U-shaped profile (p = 0.02). Intraperitoneal IL-6 was the significant and positive determinant of the time course of the D/P creatinine ratio (p < 0.0001). Effluent CA-125 decreased with time on peritoneal dialysis (p = 0.013). CONCLUSIONS: Baseline peritoneal fast transport was not associated with systemic inflammation, but was related to peritoneal locally produced substances able to mediate transitory hyperpermeability. The D/P creatinine ratio changed during the follow-up period with a U-shaped profile. This was associated with effluent IL-6 and partly with VEGF. CA-125 decreased throughout the follow-up period. PMID- 17284897 TI - Guidelines are usually the safer road. PMID- 17284896 TI - Reproducibility of renal function measurements in adult men with diabetic nephropathy: research and clinical implications. AB - BACKGROUND/AIM: Measurement of the renal function is critical to follow progression of kidney disease. Short-term and long-term variabilities in these measurements have significant impacts on clinical decision making and clinical trials. The goal of this study was to describe the variability in these measurements and to calculate minimum sample size estimates over varying time frames for clinical trials. METHODS: We studied 44 elderly men with diabetic nephropathy who participated in a clinical trial. Glomerular filtration rate and renal plasma flow were measured by continuous infusion technique with five urine collection periods on two occasions 4 months apart. Protein and creatinine excretion rates were measured in the same specimens. In addition, two consecutive 24-hour specimens every month for 4 months were collected to analyze urine protein, creatinine, urea nitrogen, and electrolytes. A hierarchical random effects model was used to analyze the reproducibility from hour to hour, from day to day, and from month to month. RESULTS: A total of 824 urine specimens were analyzed, of which 412 constituted specimens collected in the short term and 412 were 24-hour urine collections. Hour-to-hour variation accounted for 45% for urinary clearance of iothalamate, but for only 0.5% of the variability in plasma clearance of iothalamate. Day-to-day variability in 24-hour urinary excretion rates for creatinine was 46% and for protein 10%. Month-to-month variability in 24-hour excretion rates for creatinine was 11% and for protein 19%. The urine protein/creatinine ratio had a day-to-day variability of 2% and a month-to-month variability of 19%. Sample size requirements can be reduced by correcting for urine creatinine for some but not all urinary analytes. CONCLUSIONS: In nephrotic men with diabetic nephropathy, the coefficient of variation in the month-to-month protein excretion rate is 36%. Approximately 28 patients in each arm of two groups are needed to detect a difference in protein excretion rate of 28% (1 g/day in this study). The coefficient of variation in plasma iothalamate clearance over 4 months is 16%. To detect a 10% change in glomerular filtration rate between two groups, 44 patients per group are needed. To be deemed statistically significant, a change in daily protein excretion rate of at least 72% over month(s) is needed in individual patients. PMID- 17284898 TI - Association of electrocardiographic abnormalities with cardiac findings and neuromuscular disorders in left ventricular hypertrabeculation/non-compaction. AB - INTRODUCTION AND OBJECTIVES: Left ventricular hypertrabeculation/non-compaction (LVHT) is a cardiac abnormality characterized by prominent trabeculations and intertrabecular recesses, and frequently associated with neuromuscular disorders (NMD). The aim of the study was to assess the prevalence of electrocardiographic (ECG) abnormalities in LVHT and its association with clinical symptoms, left ventricular size, wall thickness, systolic function, location and extension of LVHT and presence or absence of NMD. METHODS AND RESULTS: In 86 patients LVHT was diagnosed echocardiographically between June 1995 and December 2004 (21 female, 65 male, age: 14-94 years, mean age: 52 +/- 14 years). All patients underwent a baseline cardiologic investigation and were invited for a neurologic investigation. A specific NMD was diagnosed in 21 (metabolic myopathy, n = 14; Leber's hereditary optic neuropathy, n = 3; myotonic dystrophy, n = 2; Becker muscular dystrophy, n = 1; Duchenne muscular dystrophy, n = 1), a NMD of unknown etiology in 32, the neurologic investigation was normal in 13, and 20 patients refused. Only 9 patients (10%) had normal ECGs. Frequent ECG abnormalities were tall QRS complexes (43%); ST/T-wave abnormalities (37%) and left bundle branch block (20%). ECG abnormalities were related with symptoms of heart failure and echocardiographic findings of systolic dysfunction and valvular abnormalities. Only atrial fibrillation (9%) was related to extension of LVHT. ECG abnormalities did not differ between patients with and without NMD. CONCLUSION: ECG abnormalities are frequent in LVHT. A normal ECG, however, does not exclude LVHT. No ECG pattern is typical for LVHT. ECG abnormalities occur independently of presence or absence of NMD, and thus all patients with LVHT should be referred to the neurologist. PMID- 17284899 TI - Correlation of postural blood pressure test and head-up tilt table test in patients with vasovagal syncope. AB - BACKGROUND: Vasovagal syncope is triggered by complex cerebral and cardiovascular reflex mechanisms leading to general vasodilatation and bradycardia resulting in cerebral hypoperfusion. METHODS: We prospectively studied the correlation of postural blood pressure test (PBT) and head-up tilt table test (TT) in patients with recurrent vasovagal syncope. Sixty-eight patients (37 male, 52.4 +/- 18.6 years) were included in the trial. They were asked to participate in a PBT and a TT. Independent samples t-test, ANOVA and Fisher's exact test were used for statistical analysis. p values <0.05 were considered statistically significant. RESULTS: Thirty patients (44%) showed a positive TT and thirty-four patients (50%) had a positive PBT. PBT did not show any correlation with TT, although pathophysiological mechanisms in vasovagal syncope and orthostatic hypotension are supposed to be similar. Furthermore neither TT nor PBT nor their combination had any predictive value for the patient's risk of syncope recurrence. CONCLUSIONS: TT and PBT are not correlated with each other. Both investigations cannot predict the patient's risk of syncope recurrence. PMID- 17284900 TI - Impact of serum C-reactive protein elevation on the left ventricular spherical change and the development of mitral regurgitation after anterior acute myocardial infarction. AB - BACKGROUND/AIMS: Mitral regurgitation (MR) is frequently observed in patients with acute myocardial infarction (AMI), and is known to convey an adverse prognosis. We sought to clarify the relationship between MR and left ventricular (LV) remodeling, in association with serum C-reactive protein (CRP) elevation. METHODS/RESULTS: A total of 181 patients with first anterior ST-elevation AMI were examined. MR was detected in 68 patients by color Doppler echocardiography 2 weeks after AMI, and the patients with MR were associated with higher incidence of readmission for heart failure. Serum CRP was serially measured, and the peak serum CRP level was markedly increased in patients with MR compared with those without MR. Multiple logistic regression analysis showed that peak CRP tertile was an independent determinant of MR after AMI (p < 0.0001). In the substudy, the increases in LV end-diastolic volume and sphericity index were higher in patients with MR than in those without MR. CONCLUSIONS: MR during the early phase of anterior AMI was associated with LV spherical change and late-phase heart failure, in association with increased serum CRP level. These findings suggest an important role of the inflammatory response in the development of ischemic MR and LV remodeling. PMID- 17284901 TI - Military cardiology under a tent. AB - As Operation Iraqi Freedom enters its third year, the multinational military force remains engaged in a complex mission based on the military and political climate in the Middle East. As US Navy cardiologists deployed to Kuwait, our experiences proved diverse as we learned to practice in an austere environment. From the evaluation of chest pain to the treatment of coronary artery disease and arrhythmia, patient care was tempered by our ability to use our clinical acumen, physical exam and basic objective data to establish definitive dispositions. Given our younger patient population, involvement in primary prevention efforts was a large focus, allowing us to gain a new perspective on the role of the subspecialist in changing patients' mindsets and lifestyles. By combining the basic tenets of our cardiology training with the practical aspects of diagnosing and treating in a war zone, we developed a great respect for the management of cardiac patients under challenging and often limited conditions. Our experiences as cardiologists in the desert were truly diverse and encompassed virtually every aspect of cardiovascular medicine, involving both current and historic treatment perspectives. Many unique, lifelong lessons were learned. PMID- 17284902 TI - The role of amiodarone in recent-onset atrial fibrillation after ibutilide has failed to restore sinus rhythm. AB - BACKGROUND: Ibutilide is a class III antiarrhythmic drug that is used for the cardioversion of atrial arrhythmias, but it can cause torsades de pointes. Amiodarone is also used for the cardioversion of atrial fibrillation and prolongs the QT interval but rarely causes torsades de pointes. METHODS AND RESULTS: The study included 51 consecutive patients with recent onset atrial fibrillation in whom the administration of ibutilide failed to restore sinus rhythm. In those patients we decided to proceed to intravenous administration of amiodarone. The QT intervals were measured on 12-lead ECG. After 11 +/- 5 h of the administration of the amiodarone, 42 patients (82%) were on sinus rhythm. There was no episode of non-sustained torsades de pointes or hypotension that followed the administration of the two antiarrhythmic agents. CONCLUSIONS: The administration of amiodarone in the case of ibutilide failure may be a useful adjunct to current cardioversion protocols for recent onset atrial fibrillation. PMID- 17284904 TI - Aquarium sign in the left atrium. AB - A 50-year-old man presented with fever and chest pain. Later on the same day, he developed ischemic stroke and deteriorated into loss of consciousness. A trans thoracic echocardiography showed air bubbles in the left atrium, resembling the floating bubbles in an aquarium. After further workups, atrio-esophageal fistula was diagnosed. To the best of our knowledge visualization of atrio-esophageal fistula by echocardiography has never been described previously. PMID- 17284903 TI - Upregulation of the water channel aquaporin-4 as a potential cause of postischemic cell swelling in a murine model of myocardial infarction. AB - Ischemia of the myocardium is generally accepted to be characterized by swelling of myocytes resulting in cardiac dysfunction. However, data are limited concerning the molecular mechanisms of fast water fluxes across cell membranes in ischemic hearts. Since aquaporin-4 (AQP4) is a water channel with an enormous water flux capacity, we investigated in this study whether this water channel protein might play a role in myocyte swelling following myocardial infarction. For this purpose, we studied the expression of AQP4 mRNA at different time points of ischemia in a murine model of myocardial infarction. We observed a significant correlation between the upregulation of AQP4 mRNA and the size of the infarction. In situ hybridization experiments showed comparably higher expression levels of AQP4 mRNA in ischemic myocytes, and anti-AQP4 immunoreactivity was found to be stronger in the sarcolemma of ischemic myocytes. Our findings imply a role of AQP4 in the formation of myocardial edema and this might be important for future prevention and treatment strategies of this distressing situation in order to minimize cardiac dysfunction and mortality in a variety of cardiac diseases in which cell swelling is prevalent. PMID- 17284905 TI - Implantable cardiac defibrillator placement in a patient with persistent left superior vena cava and Brugada syndrome. AB - A 45-year-old man was diagnosed with new-onset atrial fibrillation. Control of ventricular rate led to spontaneous conversion to sinus rhythm. Subsequent electrocardiograms revealed ST segment changes characteristic of Brugada syndrome. Electrophysiology study demonstrated inducible ventricular fibrillation. During the placement of an implantable cardiac defibrillator the patient was found to have a persistent left superior vena cava. Persistent left superior vena cava is present in 0.3% of cases in autopsy series. To date, persistent left superior vena cava has not been reported in association with Brugada syndrome. We report such a case. PMID- 17284906 TI - Lipoprotein(a) and LDL particle size are related to the severity of coronary artery disease. AB - BACKGROUND: The pathophysiological role and metabolic pathway of Lp(a) have not been clearly defined. An association between Lp(a) and oxidative low-density lipoprotein (LDL) were recently reported. And small dense LDL (sd-LDL) were associated with circulating malondialdehyde-modified LDL. We investigated the relationships between serum Lp(a) level and LDL particle size in coronary artery disease (CAD) patients. Further, we investigated the relationships of sd-LDL and Lp(a) with the extent and severity of CAD. METHODS: A total of 490 patients (mean: 60.5 +/- 11.5 years old) who underwent coronary angiography to evaluate chest pain were investigated. Patients were classified into two groups, a CAD group (n = 256), who had significant stenosis observed by coronary angiogram, and a control group (n = 234), who had normal, or minimal coronary arteries. CAD severity was measured by Gensini scores. The distribution of the LDL subfraction was analyzed using a Quantimetrix Lipoprint LDL System. RESULTS: The serum Lp(a) concentration was correlated with the fraction of sd-LDL (r = 0.193, p < 0.001) and mean LDL size (r = 0.160, p = 0.003). The Lp(a) level and mean LDL particle size were significantly correlated with a high Gensini score. LDL particle size in the CAD group was smaller than in the control group (26.74 +/- 0.64 vs. 26.43 +/- 0.93 nm, p < 0.001). The Gensini score was significantly higher in small LDL with high Lp(a) level groups. CONCLUSION: The positive correlation of the level of Lp(a) and sd-LDL fraction were demonstrated. The mechanism of this association is not clearly defined; we can suggest that it may stem from the individual atherogenic condition that linked to increased oxidative stress. Both increased Lp(a) and sd-LDL fraction were correlated with the severity of CAD. PMID- 17284907 TI - Long-term effects of atrial synchronous ventricular pacing on systolic and diastolic ventricular function in patients with normal left ventricular ejection fraction. AB - BACKGROUND: Atrial synchronous right ventricular pacing (VP) may compromise ventricular function in patients undergoing pacemaker implantation for atrioventricular block. We assessed the usefulness of tissue Doppler imaging (TDI) and color M-mode echocardiography in evaluating patients with VP, and examined the long-term effects of VP on ventricular function by echocardiographic indices and B-type natriuretic peptide (BNP) measurements. METHODS: We studied 60 clinically stable elderly dual-chamber pacemaker recipients (mean age: 74 +/- 9 years) who had normal left ventricular (LV) systolic function and on the long term the same cardiac rhythm, either intrinsic normal ventricular activation (IA) (n = 20), or VP (n = 40). RESULTS: Paced patients, compared to patients with IA, had decreased stroke volume (p < 0.05) and a more depressed relaxation pattern, as indicated by decreased peak early mitral velocity (E)/peak atrial contraction velocity ratio and tissue Doppler imaging (TDI)-early transmitral diastolic velocity (Ea) measures (p < 0.05). Both groups presented similar BNP levels and LV filling pressures, as assessed by E/Ea and E/early diastolic transmitral flow propagation velocity. In VP patients, age (beta = 0.31), Ea (beta = -0.28) and E/Ea (beta = 0.32) emerged as independent predictors of BNP levels. CONCLUSIONS: VP is associated with reduced LV systolic function and signs of impaired relaxation. Elevated BNP levels in elderly VP patients with normal ejection fraction may be predicted by TDI signs of LV diastolic dysfunction. PMID- 17284908 TI - A pilot study of the use of oral health-related quality of life measures as an outcome for analysing the impact of caries disease among Swedish 19-year-olds. AB - OBJECTIVES: To be useful as a supplement for health economic evaluations in caries preventive care, the oral health-related quality of life (OHRQOL) measures must be able to discriminate for caries disease. The aim of this study was therefore to explore whether any differences existed in perceived OHRQOL among adolescents with either high or no caries experience. METHODS: Eighty-two individuals (all 19-year-olds) agreed to participate in a pilot exploratory case control study. Thirty individuals with high caries experience formed the test group. The control group consisted of 52 individuals with no caries experience, selected randomly from a caries-free population. OHRQOL scores were collected for analysis through personal interviews using two OHRQOL measures, the Child Perceptions Questionnaire (CPQ(11-14)) and Oral Health Impact Profile-14 (OHIP 14). RESULTS: The OHRQOL measures used were not able to discriminate between young adults with high and no caries risk experience with respect to perceived OHRQOL. Despite a consistently higher impact score for the test group throughout the overall and subscale scores, the differences were not statistically significant except for one of the subscale scores, oral symptoms. CONCLUSIONS: This study indicates that the prevalence and incidence of caries must be seen as too low in Sweden to have major influence on young adults' perceived OHRQOL and well-being. Therefore, the usefulness of OHRQOL measures in supplementing outcome measurement in health economic evaluations, particularly those that focus on caries preventive strategies, must be questioned. PMID- 17284909 TI - Chlorhexidine and preservation of sound tooth structure in older adults. A placebo-controlled trial. AB - The Trial to Enhance Elderly Teeth Health (TEETH) was designed to test the impact of regular rinsing with a 0.12% chlorhexidine (CHX) solution on tooth loss, and the causes of tooth loss (caries, periodontal disease and trauma) were also investigated. This paper reports on the effectiveness of a 0.12% CHX solution for controlling caries using a tooth surface (coronal and root) survival analysis. A total of 1,101 low income elders in Seattle (United States) and Vancouver (Canada), aged 60-75 years, were recruited for a double-blind clinical trial and assigned to either a CHX (n = 550) or a placebo (n = 551) mouth rinse. Subjects alternated between daily rinsing for 1 month, followed by weekly rinsing for 5 months. All sound coronal and root surfaces at baseline were followed annually for up to 5 years. At each follow-up examination, those tooth surfaces with caries, restored, or extracted were scored as 'carious'. The hazard ratio associated with CHX for a sound surface to become filled, decayed, or extracted was 0.87 for coronal surfaces (95% confidence interval: 0.71-1.14, p = 0.20) and 0.91 for root surfaces (95% confidence interval: 0.73-1.14, p = 0.41). These findings suggest that regular rinsing with CHX does not have a substantial effect on the preservation of sound tooth structure in older adults. PMID- 17284910 TI - Antibacterial effect of chlorhexidine- containing glass ionomer cement in vivo: a pilot study. AB - This in vivo pilot study was carried out to test the antibacterial effect of glass ionomer containing chlorhexidine (test group) in comparison to conventional glass ionomer (control group). Fifty 6- to 11-year-old children with one occlusal lesion in a molar were randomly allocated to test and control groups in a parallel-group design. The cavity walls and one half of the floor were cleaned and restored with one of the materials without dentine conditioning. The restorations were removed after 7 days. Dentine samples were taken from the cleaned (affected dentine) and noncleaned area (infected dentine) at baseline and at day 7. Samples were anaerobically and aerobically cultivated for mutans streptococci, lactobacilli and total viable bacterial count (TVC) following common laboratory procedures. ANCOVA was used to test for treatment effects. Seven days after treatment, a significant decrease in anaerobic and aerobic bacterial counts (p = 0.0001) was shown. Lower numbers of anaerobic lactobacilli (p = 0.02), TVC (p = 0.008) and aerobic lactobacilli and TVC (p = 0.03), but not of mutans streptococci, were indicated in the test group compared to the control group. A significant reduction in aerobic lactobacilli from infected dentine treated with the glass ionomer containing chlorhexidine (p = 0.05) was observed whereas in affected dentine, anaerobic mutans streptococci, lactobacilli and TVC and aerobic TVC and mutans streptococci were significantly lower in the test group 7 days after treatment (p = 0.01). We conclude that the present pilot study revealed lower microorganism counts in chlorhexidine-containing glass ionomers than in conventional glass ionomers for both affected and infected dentine over a 7-day period. PMID- 17284911 TI - Effects of various forms of calcium added to chewing gum on initial enamel carious lesions in situ. AB - The purpose of this randomized, cross-over in situ study was to determine the effects of 4 chewing gums on artificial caries-like subsurface lesions. Two chewing gums (1 with zinc citrate and 1 without) contained dicalcium phosphate (3.9%), calcium gluconate (1.8%) and calcium lactate (0.45%), 1 chewing gum contained casein phosphopeptide-amorphous calcium phosphate nanocomplexes (0.7%), and another one contained no calcium. Fifteen subjects without current caries activity (7 male, 8 female; mean age: 27.5 +/- 2.5 years) wore removable buccal appliances in the lower jaw with 4 bovine enamel slabs with subsurface lesions. The appliances were inserted immediately before gum chewing for 20 min and then retained for an additional 20 min. This was performed 4 times per day. Every subject chewed 4 different chewing gums over 4 periods of 14 days each. During a fifth period (control) the subjects only wore the appliances without chewing gum. At completion of each period the enamel slabs were embedded, sectioned and subjected to transversal microradiography. With regard to change of mineral loss and of lesion depth no significant differences could be found between chewing gums containing calcium and calcium-free chewing gums. Moreover, the chewing gum groups and the control group did not differ significantly if adjustments were made for baseline values (p > 0.05; ANCOVA). Under the conditions of the present study it may be concluded that the use of chewing gum offers no additional remineralizing benefit to buccal tooth surfaces, even if the chewing gum contains calcium compounds. PMID- 17284912 TI - Comparison of paired visual assessment and software analyses of changes in caries status over 6 months from fluorescence images. AB - Images captured using light-induced fluorescence systems are generally analysed using proprietary software. The purpose of this study was to determine if such images could be scored visually and to compare these data with those metrics produced by the software. A total of 171 lesions were selected from a pool of images to provide a range of lesions which were reported as having remained static, increased or decreased in fluorescence using the QLF analysis software. The baseline and 6-month images were then assessed side by side on a computer screen by 10 examiners who were asked to rate the lesions to determine if the lesion had become better or worse, or had stayed the same. There was generally poor correlation between clinical visual image assessments and all QLF analysis outcomes for all examiners. The agreement amongst the visual image assessments for the 10 examiners compared to the average score ranged from kappa 0.22 to 0.59 and the rank correlations from -0.01 to 0.73. This study suggests that the visual assessment of lesion images by the examiners in this study was based upon different characteristics of lesion change than those utilised by the QLF analysis software. A clearer understanding of lesion characteristics that are indicative of positive and negative changes may be required before this technology can be exploited to its full potential. PMID- 17284913 TI - Accuracy and reproducibility of conventional radiographic assessment and subtraction radiography in detecting demineralization in occlusal surfaces. AB - Subjective interpretation of paired digital radiographic images viewed side by side to assess occlusal lesion progression, arrest or remineralization is difficult. The aim of this study was to compare the accuracy and reproducibility of a digital subtraction radiography technique and visual assessment of paired digital images in detecting changes in mineral content within occlusal cavities. Forty molar teeth with occlusal cavities were placed in arches and baseline digital radiographs taken. Nineteen teeth were randomly selected and had acid placed in the cavities and digital images taken after 3, 6, 12, 18 and 24 h of acid exposure. Paired baseline images and those taken at the various time intervals were examined side by side and assessed for demineralization by five examiners. Subtraction images prepared from the paired images were assessed in the same way. One fifth of the images were re-examined to determine intra examiner reproducibility. After 12 h or longer the diagnostic accuracy (mean area under the ROC curve = 0.92-0.98 for subtraction radiography), intra-examiner and inter-examiner reproducibility for detection of demineralization from the subtraction images was significantly better than viewing the paired images side by side (p < 0.01). The subtraction radiography system used was found to be more accurate and reproducible than visual assessment of paired digital images. As such the technique shows promise for monitoring occlusal lesion progression in clinical studies. PMID- 17284914 TI - An X-ray microtomography study on the mineral concentration of carious dentine removed during cavity preparation in deciduous molars. AB - Dentists use a number of criteria in order to assess when a cavity is caries free, amongst which hardness is probably the most widely used. However, the judgement is subjective. X-ray microtomography (XMT) is a non-destructive microscopic technique that allows in vitro specimens to be scanned, manipulated and then rescanned. In this study, a high-definition XMT scanner was used to determine the mineral distribution of carious dentine in 10 deciduous molars, and the extent of dentine removed by an experienced clinician was investigated. For each tooth, after an initial XMT scan, caries was removed using a steel bur in a slow hand-piece. The tooth was then repositioned and rescanned. Mineral concentrations were calculated from the linear attenuation coefficients assuming the mineral phase to be hydroxyapatite and the organic phase to be collagen. The volume of dentine tissues removed was calculated by subtracting data of the second scan from the first. The results showed that the mean modal mineral concentration for the 10 teeth was 1.42 g x cm(-3) for sound dentine. Because of uncertainty about collagen concentration in carious dentine, the mean modal mineral concentration for the carious dentine had a range of 0.37-0.5 g x cm(-3). It was found that the subjective criteria used by the operator could lead to inconsistency of cavity preparation. The cavities could be overprepared by 8.5 44.3% in volume. However, the overpreparation was not uniform throughout the cavity: residual demineralised dentine could still be detected in the postoperative scan in isolated regions. PMID- 17284915 TI - Laser fluorescence measurements compared to electrical resistance of residual dentine in excavated cavities in vivo. AB - It has been suggested that laser fluorescence close to the dental pulp shows higher values than more distant measurements. The aim of this study was to assess fluorescence on the cavity floor and to correlate these measurements with electrical resistance as a measure of residual dentine thickness. Thirty carious lesions were excavated with a bur. The endpoint of caries removal was determined by visual, tactile and auditory means. Fluorescence was measured with the Diagnodent device and with the fluorescence feedback system of a therapeutic Er:YAG laser. Electrical resistance of the residual dentine (Prepometer units, PU) was measured with a proprietary device. Significant differences were observed between the fluorescence systems (p < 0.05). For Diagnodent, a decrease of electrical resistance of the residual dentine resulted in an increase of the fluorescence values of 2.99 units/PU (95% CI = 2.00-3.97) and an increase of 0.30 units/PU (95% CI = 0.19-0.40) for the fluorescence feedback system. For zero electrical resistance, a predicted maximum value of 51.5 units (95% CI = 41.3 61.7) was calculated for the Diagnodent and 5.1 units (95% CI = 4.1-6.2) for the feedback system. The study indicates that using the suggested detection cut-off with the Diagnodent device may be not suited to assess the endpoint of caries removal close to the dental pulp. Employing the Key Laser III, values up to 6 units might be caused solely by close proximity to the pulp, which should be considered when caries removal by laser is controlled by laser fluorescence feedback. PMID- 17284916 TI - Effect of titanium tetrafluoride and sodium fluoride on erosion progression in enamel and dentine in vitro. AB - Our aim was to investigate the effect of TiF4 solutions on mineral loss on enamel and dentine in vitro. Samples were fluoridated 1 x 5 min per day with 1.64% w/v TiF4 or 2.2% w/v NaF solutions, each with a pH of 1.2, and then subjected to a cyclic de- and remineralization procedure for 5 days. Demineralization was performed for 6 x 10 min per day with citric acid (pH 2.3). In controls no fluoridation was performed. Mineral content was determined by longitudinal microradiography. Enamel mineral loss was markedly reduced by both fluoride solutions, but TiF4 was significantly more effective than NaF: cumulative mineral loss on day 3 was 61.7 +/- 15.0 microm in the NaF and 34.2 +/- 13.1 microm in the TiF4 group (p < or = 0.001) compared with 121.0 +/- 27.0 microm in the control group. Dentine mineral loss ceased after both TiF4 and NaF applications (cumulative mineral loss on day 5 in controls: 61.0 +/- 17.0 microm, in the TiF4 group: 15.4 +/- 13.4 microm and in the NaF group: 21.8 +/- 11.8 microm). Both TiF4 and NaF application reduced mineral loss both on enamel and dentine, which could open new possibilities for a symptomatic therapy of erosions. PMID- 17284917 TI - Efficacy of waiting periods and topical fluoride treatment on toothbrush abrasion of eroded enamel in situ. AB - The aim of this study was to investigate the effectiveness of both waiting periods between acid exposure and tooth brushing and fluoride applications in preventing toothbrush abrasion of acid-softened enamel surfaces. The study, on 5 subjects, had an in situ crossover design with experimental periods of 5 days each. Human enamel samples were recessed in mouth appliances and at the end of each experimental period, enamel loss was determined profilometrically. Specimens were eroded extraorally (2 x 20 min per day; 0.05 M citric acid), standardized brushing (2 x 30 s per sample per day; powered toothbrush) was performed in situ. The groups were: (1) erosion only, (2) brushing with fluoride-free toothpaste directly after, (3) 2 h after, or (4) before erosion; fluoride application was either (5) brushing with a fluoride toothpaste or (6) brushing with a fluoride toothpaste or gel, and rinsing with a fluoride mouth rinse. Enamel loss was (1) 45.2 +/- 10.8, (2) 79.3 +/- 7.8, (3) 81.7 +/- 9.5, (4) 69.7 +/- 13.8, (5) 51.5 +/ 13.0, and (6) 41.2 +/- 1.8 microm. Brushing without fluoride increased the enamel loss significantly (p < or = 0.001), waiting for 2 h had no protective effect, and brushing before erosion decreased enamel loss values only by 12% (n.s.). In the fluoride groups, enamel loss was significantly lower than after brushing with the fluoride-free toothpaste and comparable to values after erosion only (n.s.). Waiting periods had only a minor effect, whilst the application of fluoride appeared promising. PMID- 17284919 TI - Changes in electrical resistance of sound fissure enamel in first molars for 66 months from eruption. AB - The purposes of this study were to investigate the enamel maturation process in the occlusal pit of sound first molars by measuring electrical resistance. Ninety nine sound first molars in 34 children (mean age of 6.47 +/- 0.51 years) were measured electrically once every 6 months and were monitored for a maximum of 66 months. Electrical resistance increased during the posteruptive period. However, the results suggest that posteruptive enamel maturation in the occlusal pits may not be completed even 66 months after tooth eruption. PMID- 17284918 TI - Demineralisation of permeable hydroxyapatite with alternating water and acidic buffer: scanning microradiographic study of effect of switching period. AB - Permeable hydroxyapatite (HAP) blocks were exposed for equal times alternately to pH 4.0 buffer and water for 237 h. Rates of HAP loss with time (determined from changes in X-ray attenuation) were measured as a function of switching period tau (the time for a complete cycle) from 0.5 to 6 h and with a continuous buffer flow. The mean rate of HAP loss decreased markedly as tau increased, and for large tau was about half the rate for continuous buffer flow. We propose that demineralising conditions through the depth of the HAP are influenced by the extent of retention of buffer within its pores which will depend on tau. A mathematical model with parameters R(0) and Deltat was developed, where R(0) is the rate of demineralisation for continuous flow, and Deltat a time added to each tau/2 buffer exposure to account for its retention in the HAP pores. Experimental data fitted the model with Deltat approximately 8 to approximately 10 min and with R(0) close to the rate observed for continuous buffer flow. The model predicts that the rate decreases and approaches R(0)/2 as tau --> infinity, as was found experimentally to be the case. This type of study could potentially give information about subsurface porosity and transport processes during acidic dissolution of permeable solids, for example in dental caries and dental erosion. PMID- 17284920 TI - Prolonged postpartum urinary retention: the importance of asking the right questions at the right time. AB - The pathophysiology of postpartum urinary retention (PUR) is still unclear. The prevalence rate varies with the definition used and the literature discusses various risk factors. Bladder catheterization is the treatment of choice, but the best way to do it is not ascertained. Long-term sequelae seem to be rare. There are no widely accepted preventive measures. Our 2 cases illustrate that it is important to prevent PUR not only by avoiding the known risk factors, but also by additionally asking for signs of voiding dysfunction postpartum. PMID- 17284921 TI - Pregnancy and delivery with Kindler syndrome. AB - BACKGROUND: Kindler syndrome is a rare, autosomal-recessive skin disease characterized by bullous poikiloderma. Mucosal manifestations are common that involve the oral cavity, esophagus, urethra and genital organs. CASE REPORT: A 37 year-old woman with Kindler syndrome received prenatal care at our hospital. Her skin disease did not change during pregnancy and puerperium. Her pregnancy course was uneventful, but an elective cesarean section was performed at 38 weeks of gestation due to vaginal stenosis. Surgical wound healing was uncomplicated. CONCLUSION: Pregnancy did not exacerbate the cutaneous symptoms of Kindler syndrome in this case. Cesarean delivery may be necessary in cases with severe genital lesions besides obstetrical indications. Careful perioperative management is needed to protect vulnerable skin and mucosa. PMID- 17284922 TI - Hypoglycemia due to ectopic release of insulin from a paraganglioma. AB - Insulin-secreting pancreatic tumors and insulin-like growth hormone-secreting non islet cell tumors can cause hypoglycemia. However, insulin-releasing paraganglioma or pheochromocytoma has almost never been reported. A 67-year-old female patient was admitted to our hospital because of headache, palpitation, perspiration, faintness, frequent sense of hunger and absent-mindedness. These intermittent symptoms had begun approximately a year before admission. On physical examination, she had high blood pressure of 150/90 mm Hg. Hormonal studies demonstrated increased urinary norepinephrine levels, and hyperinsulinemic hypoglycemia was confirmed while the patient was symptomatic. Abdominal MRI revealed a retroperitoneal mass measuring 4.5 cm in the pancreatic region. She was treated with an alpha-blocking agent to control blood pressure preceding the removal of the mass. Histopathological diagnosis was paraganglioma, and immunohistochemically insulin staining in the neoplastic cells was demonstrated. Her blood pressure normalized and hypoglycemia relieved after the operation. The patient did not have recurrence of hypoglycemia after a year of follow-up. Paraganglioma is a rare tumor of the neural crest, and co-secretion of insulin and catecholamines has been reported only by a single case report in the literature. The present patient is another case with this co-secretion. PMID- 17284923 TI - Effects of a low-fat versus a low-carbohydrate diet on adipocytokines in obese adults. AB - BACKGROUND AND AIMS: There are few studies addressing the effect of weight loss on circulating levels of adipocytokines. The aim of our study was to determine whether different diets would have different weight loss effects and to examine the changes in adipocytokine levels. METHODS: A population of 90 obesity non diabetic outpatients was analyzed in a prospective way. The patients were randomly allocated to two groups: (a) diet I (low-fat diet), and (b) diet II (low carbohydrate diet). At baseline and after 3 months on the diet, adipocytokines were evaluated. RESULTS: 43 patients were randomized to group I and 47 patients to diet group II. No differences were detected between weight loss in either group (3.3 +/- 0.51 vs. 4.4 +/- 0.6 kg; n.s.). In group I, a significant decrease in leptin levels was found. In group II, leptin and C-reactive protein (CRP) levels also decreased. The decrease in leptin levels was lower with diet I than II (16.4 vs. 22.8%; p < 0.05). CONCLUSION: The serum leptin concentration decreased due to the 3-month intervention with low-fat and low-carbohydrate diets, without changes in other adipocytokines. The decrease in leptin and CRP levels were higher with a low-carbohydrate diet than a low-fat diet. PMID- 17284924 TI - ARIA (Allergic Rhinitis and Its Impact on Asthma) classification of allergic rhinitis severity in clinical practice in France. AB - BACKGROUND: The Allergic Rhinitis and Its Impact on Asthma (ARIA) workshop proposes a classification of allergic rhinitis severity. It does not take into account impairment in quality of life and treatment should be adapted accordingly. METHODS: Two cross-sectional surveys were designed:a spring survey, for which 1,321 practitioners enrolled 3,026 patients consulting for seasonal allergic rhinitis and an autumn-winter survey, for which 1,346 practitioners enrolled 3,507 patients consulting for perennial allergic rhinitis. Simple quality of life parameters were included and logistic regressions were performed in order to assess the impairment of quality of life. RESULTS: The majority of the patients were experiencing an impairment on their quality of life (92.2%). Except for cough, these patients had significantly more nasal, lung and ocular symptoms. In a multivariate analysis, rhinorrhea, nasal itching, red eyes, dyspnea, change in voice, fatigue and headache were correlated to impairment of quality of life. Persistent rhinitis was associated only with subjects who expressed difficulties in reading, and intermittent rhinitis with those who had to blow their nose and who expressed an impact on their professional activities. CONCLUSIONS: The proposal of the ARIA expert panel defining the severity of allergic rhinitis based on quality of life parameters is likely to simplify daily physician practice. PMID- 17284925 TI - ACP1 and Th class of immunological disease: evidence of interaction with gender. AB - BACKGROUND: Data collected by our group in the past years indicate a relationship between ACP1 genetic polymorphism and susceptibility/resistance to immunological diseases. Recent observations suggest that through modulation of ZAP-70 activity, the enzyme may influence T cell activation. In view of the current interest in gender differences in autoimmune diseases we reviewed our data to enlighten possible effects of gender on the relationship between ACP1 and class of immunological disease. METHODS: We studied three samples of subjects with allergic disorders of a total of 299 subjects, 71 subjects with Crohn's disease and 188 children with type 1 diabetes. Three-way contingency tables were analyzed by a log linear model and two-way contingency tables by chi(2) test. RESULTS: There is an association between ACP1 and allergy (Th2 class) that depends on gender: the presence of the ACP1*A allele seems to make females more susceptible to allergic manifestations as compared to males. ACP1 is also associated with Crohn's disease and type 1 diabetes: the relationship between this class (Th1) of immunological diseases and ACP1 depends on gender. The presence of *A allele seems to make females less susceptible to this class of diseases as compared to males. CONCLUSIONS: The ACP1*A allele which is associated with low ACP1 activity appears responsible for a complex relationship involving gender, ACP1 and Th1/Th2 orientation. Low ACP1 activity influencing ZAP-70 activity and in turn T cell activation seems to have opposite effects on Th1/Th2 orientation depending on gender. PMID- 17284926 TI - Analysis of components of the CD14/TLR system on leukocytes of patients with atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) is frequently associated with skin infections that may be a consequence of an impaired function of the innate immune response. Conversely, the frequent bacterial colonization may also influence the systemic immune reactions, including the Toll-like receptor (TLR) system, through the translocation of bacterial components into the circulation. Therefore, we characterized phenotypic and functional properties of the TLR system in patients with extrinsic and intrinsic AD. METHODS: The absolute number of surface CD14, TLR2, TLR4 and CD180 and the CD14-mediated uptake of bodipy-labeled endotoxin and bacteria by whole blood leukocytes was studied by flow cytometry. We measured the serum soluble CD14 concentration by an inhibitory flow cytometric method. RESULTS: We observed a significant overexpression of TLR2 and TLR4 on monocytes, TLR2 and CD14 on granulocytes and CD180 on lymphocytes of intrinsic AD patients compared to healthy controls. The serum soluble CD14 was not different in the intrinsic AD patients, while it was diminished in the extrinsic AD group compared to the controls. The endotoxin and bacterium uptake showed no differences. CONCLUSIONS: The observed upregulation of CD14, TLR2, TLR4 and CD180 on peripheral leukocytes seems to be rather a consequence than the cause of the repeated bacterial infections in AD. PMID- 17284927 TI - An observational study on outgrowing food allergy during non-birch pollen specific, subcutaneous immunotherapy. AB - BACKGROUND: Birch pollen-specific immunotherapy (SIT) decreases allergy to foods containing birch pollen-homologous allergens. Cross-reactivity was also observed between plane tree pollen and some vegetable foods. OBJECTIVE: The aim of this study was to evaluate the outgrowing of food allergy by patients suffering from vegetable food allergy associated with plane tree pollinosis (rhinoconjunctivitis and/or asthma) during plane tree pollen SIT. METHODS: An observational and prospective study was conducted in 16 adult patients suffering from vegetable food allergy (hazelnut, walnut, lettuce, peach and cherry) and from plane tree pollinosis receiving plane tree pollen SIT for 1 year. Open oral challenges with the implicated food were performed before and after SIT. Blood samples were drawn for measurement of pollen- and food-specific IgE and IgG4 before and after treatment. RESULTS: Plane tree SIT resulted in a significant decrease in food allergy, since the mean food quantity provoking objective symptoms increased from 2.19 to 13.74 g (p < 0.05), and 6 of the 11 patients tolerated the highest level (25 g) of the challenged food after plane tree SIT. Laboratory data also showed a decrease in IgE levels and an increase in IgG4 levels after immunotherapy. CONCLUSION: SIT with plane tree pollen has a positive impact on food allergy in plane tree pollen-allergic subjects. PMID- 17284928 TI - A novel missense mutation in CIAS1 encoding the pyrin-like protein, cryopyrin, causes familial cold autoinflammatory syndrome in a family of Ethiopian origin. AB - BACKGROUND: Cold-induced urticaria is a form of physical urticaria which is characterized by rapid onset of pruritus, erythema, and swelling after exposure to a cold stimulus. Familial cold autoinflammatory syndrome (FCAS) is a rare autosomal-dominant condition characterized by unremitting attacks of cold-induced urticaria, often accompanied by other systemic manifestations. The disorder was previously shown to be caused by mutations in CIAS1, encoding a pyrin-like protein also involved in the pathogenesis of Muckle-Wells syndrome (MWS), and chronic infantile neurological cutaneous and articular syndrome (CINCA). METHODS: In the present study, using direct sequencing, we assessed a two-generation family of Jewish Ethiopian origin, including 3 members affected with FCAS. RESULTS: We identified a novel CIAS1 mutation, F525C. The mutation was shown to affect a highly conserved residue of the protein and to segregate with the disease throughout the extended family. CONCLUSIONS: Our results add to the expanding spectrum of mutations in CIAS1 and provide evidence for striking phenotypic heterogeneity in inherited autoinflammatory syndromes. This is the first report of inherited cold urticaria in a family of Ethiopian origin. PMID- 17284929 TI - Lys, pro and trp are critical core amino acid residues recognized by FUM20, a monoclonal antibody against serine protease pan-fungal allergens. AB - BACKGROUND: Alkaline/vacuolar serine proteases comprise a major group of pan fungal allergens from several prevalent airborne fungal species. It is of importance to characterize antigenic determinant(s) recognized by monoclonal antibodies against these major allergens. METHODS: The antigenic determinant of fungal serine proteases recognized by a monoclonal antibody, FUM20, was analyzed by dot immunoassay of synthetic peptides immobilized on cellulose membrane. Results obtained were confirmed by wild-type recombinant protease and its mutants. The epitopes were mapped to the structure of serine proteases by molecular modeling. RESULTS: A linear epitope encompassing 9 amino acids from Pen ch 18 ((6)EKNAPWGLA(14)) binds FUM20. The corresponding peptide ((5)AKGAPWGLA(13)) from Rho m 2 also binds FUM20. Substitution of K6, P9 or W10 with alanine in this peptide resulted in drastic loss of FUM20 binding. Rho m 2 mutants with single K6A, P9A, P9G, W10A or W10F substitute showed negative immunoblot reactivity against FUM20. However, the Rho m 2 K6R mutant can bind FUM20. Three-dimensional structural models of the FUM20 antigenic determinants on serine proteases were constructed. The lysine residue critical for FUM20 interaction is on the surface of the proteases and solvent accessible. The critical core residue proline is located at the beginning of an alpha-helix. CONCLUSIONS: The lysine, proline and tryptophan residues located on the N terminal region of fungal serine proteases are critical core amino acid residues recognized by FUM20, a monoclonal antibody against serine protease pan-fungal allergens. These findings advance our understanding of the antigenic structures responsible for the antigenicity of serine protease allergens. PMID- 17284930 TI - Polymerase chain reaction (PCR) technology. PMID- 17284931 TI - Neuroprotective and intraocular pressure-lowering effects of (-)Delta9 tetrahydrocannabinol in a rat model of glaucoma. AB - In glaucoma, retinal ganglion cell (RGC) death is induced by many risk factors, including ocular hypertension. It has been proposed that glutamate-mediated oxidative stress may also contribute to this RGC death. Cannabinoids are known to possess therapeutic properties including ocular hypotension and antioxidation. In this study, we test the hypothesis that (-)Delta(9)-tetrahydrocannabinol (THC) lowers intraocular pressure (IOP) and prevents RGC death in a rat model of glaucoma. Arat model of experimental glaucoma with chronic, moderately elevated IOP was produced unilaterally by cauterization of episcleral vessels. Rats received weekly injections of THC at a level of 5 mg/kg or vehicle for 20 weeks. IOP of both eyes was measured weekly on anesthetized animals immediately before THC treatment. RGCs were labeled in a retrograde fashion and counted in whole mounted retinas. IOP was elevated in all operated eyes 1 day after the operation and remained elevated in the vehicle-treated rats throughout 20 weeks. In THC treated rats, IOP elevation in operated eyes was diminished 2 weeks after operation and remained reduced. IOP in the contralateral control eyes was not affected by THC. In the operated eyes of vehicle-treated animals, there was a loss of approximately 50 and 40% of the RGCs in the peripheral and central retina, respectively. The RGC loss in the operated eyes of the THC-treated animals was reduced to 10-20%. These results demonstrate that THC is a neuroprotectant that preserves RGCs in an experimental model of glaucoma, possibly through a reduction in IOP. PMID- 17284932 TI - The response of retrobulbar vasculature to hypercapnia in primary open-angle glaucoma and ocular hypertension. AB - PURPOSE: To evaluate the physiological effects of hypercapnia on the retrobulbar vasculature in ocular hypertension (OH) and open-angle glaucoma (OAG). METHODS: Peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI) of the ophthalmic (OA) and central retinal arteries (CRA) were evaluated in 12 eyes with OH and 8 eyes with OAG using color Doppler imaging. Measurements were taken before and during hypercapnia. RESULTS: Patients with OAG were found to have increased EDV (p < 0.035) of the CRA, and decreased PSV (p < 0.097) and EDV (p < 0.098) of the OA, during hypercapnia. Patients with OH had increased PSV (p < 0.062) and EDV (p < 0.072) of the CRA during hypercapnia. Patients with OH also demonstrated a greater percent change in the calculated RI (p < 0.065) of the CRA in response to hypercapnia when compared to OAG. The mean RI of the CRA decreased during hypercapnia. DISCUSSION: Patients with OH were found to have a normal vasodilatory response within the retrobulbar vasculature during hypercapnia resulting in increased volumetric blood flow to the retina while patients with OAG did not, suggesting there is vasospasm at or downstream from the CRA resulting in decreased volumetric blood flow to the retina. PMID- 17284933 TI - Pharmacokinetics of terbinafine in the rabbit ocular tissues after topical administration. AB - OBJECTIVE: To determine the distribution of terbinafine in the cornea and aqueous humor after topical administration. METHODS: A corn oil ointment of terbinafine 0.2% (resolved in sterile corn oil) was applied to the conjunctival sac of albino rabbits twice (with a 5-min interval). The concentration of terbinafine was determined with high-performance liquid chromatography (HPLC) 5, 15, 30, 60, 120 and 240 min after administration of terbinafine. RESULTS: After topical administration, the concentration of terbinafine increased gradually, reached a peak (1.39 microg/ml at 30 min in the cornea and 82.9 ng/ml at 30 min in aqueous humor, respectively) and then decreased. The concentration was 0.18 microg/g at 240 min in the cornea, but terbinafine could not be tested at 120 min in aqueous humor. CONCLUSIONS: Topical ophthalmic terbinafine 0.2% could penetrate into the cornea and aqueous humor at concentrations adequate for inhibition of fungus. PMID- 17284934 TI - AP-1 expression in ethanol-treated corneal epithelium in vivo. AB - PURPOSE: To examine the expression pattern of stress-related genes, c-fos and c jun, both the major components of activator protein-1 (AP-1), in rat corneal epithelium treated with a short-term ethanol exposure. The purpose of the current study was to examine if the ethanol exposure during laser epithelial keratomileusis (LASEK) may stimulate or damage the corneal epithelial cells. METHOD: Sixty male Wistar rats were used. Fifty microliters of 20% ethanol was placed onto a surface 2.4 mm in diameter of the central corneal epithelium for 30 s. The affected eyes, washed with saline, were then enucleated after various intervals of healing. To know the expression pattern of c-fos and c-jun mRNAs and c-Fos, c-Jun and Jun D proteins, in situ hybridization and immunohistochemistry were carried out. The expression level of c-fos and c-jun mRNAs was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Apoptotic nuclei in the tissue sections were identified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. RESULTS: Thirty to 60 min after the treatment, c-fos and c-jun mRNAs were detected in the corneal epithelium. These signals were no longer evident at 90 min. c-Fos protein was detected in the corneal epithelium around the area of ethanol exposure from 60 to 120 min after the treatment, while c-Jun protein was not detected. Jun D protein was detected in control whole corneal epithelium and not affected by ethanol exposure in the periphery. The levels of c-fos and c-jun mRNAs were increased approximately 8 times at 30 min compared with the control level. TUNEL-positive apoptotic nuclei in the tissue sections were identified. CONCLUSION: Corneal epithelial cells, especially those surrounding the ethanol exposed area, are transiently transcriptionally activated at a very early phase after the ethanol exposure. mRNA expression for c-fos is followed by protein synthesis, but that of c-jun is not followed by protein synthesis. Resistance of Jun D protein expression to ethanol suggests that it might be a candidate for an AP-1 complex with c-Fos. PMID- 17284935 TI - Pigment-epithelium-derived factor suppresses expression of receptor for advanced glycation end products in the eye of diabetic rats. AB - The interaction of advanced glycation end products (AGEs) and their receptor (RAGE) elicits inflammatory and proliferative responses in retinal vascular wall cells, thereby being involved in the pathogenesis of diabetic retinopathy. Recently, pigment-epithelium-derived factor (PEDF) has also been shown to play a role in diabetic retinopathy. However, the effects of PEDF on RAGE gene expression remain to be elucidated. Therefore, we investigated here whether PEDF could prevent diabetes- or AGE-induced RAGE gene expression and the way that it might achieve this effect. Administration of PEDF or pyridoxal phosphate, an AGE inhibitor, suppressed RAGE gene expression in the eye of streptozotocin-induced diabetic rats. Further, intravenous injection of AGEs to normal rats increased RAGE gene expression, which was also blocked by PEDF. In vitro, PEDF or an antioxidant N-acetylcysteine blocked the AGE-induced RAGE gene induction in microvascular endothelial cells. In addition, PEDF completely inhibited superoxide generation and NF-kappaB activation in AGE-exposed endothelial cells. These results demonstrated that PEDF could inhibit diabetes- or AGE-induced RAGE gene expression by blocking the superoxide-mediated NF-kappaB activation. Our present study suggests that pharmacological upregulation or substitution of PEDF may play a protective role against diabetic retinopathy by attenuating the deleterious effect of AGEs. PMID- 17284936 TI - Fluorescein angiography compared to three-dimensional measurements by the retinal thickness analyzer in classic choroidal neovascularization. AB - PURPOSE: To compare and correlate imaging of classic subfoveal choroidal neovascularization (CNV) with noninvasive 3-dimensional imaging by the retinal thickness analyzer (RTA) to conventional fluorescein angiography (FA). METHODS: A total of 29 eyes of 29 consecutive patients with predominantly classic CNV eligible for photodynamic therapy underwent FA and RTA imaging. The FA dimensions of the CNV were measured independently by two graders. With the RTA, masked to FA the size of the CNV itself as imaged in 3-dimensional reconstruction, the size of significantly thickened retina overlying the CNV and the maximum retinal thickness were measured. RESULTS: The mean diameter of the CNV determined from 3 dimensional RTA reconstructions showed an excellent correlation with measurements from FA (r = 0.91, p < 0.001). The area of retinal thickening was by a mean of 0.7 mm in diameter larger and correlated moderately well with the size of the CNV on FA (r = 0.65, p < 0.001). In contrast, there was no correlation between the absolute retinal thickness and the CNV size on FA. CONCLUSIONS: Noninvasive quantitative mapping of predominantly classic CNV by RTA is feasible and also allows 3-dimensional measurement of the lesion itself. The results correlate well with FA assessment but visualize different properties of the disease. PMID- 17284937 TI - Chorioretinal vascular oxygen tension in spontaneously breathing anesthetized rats. AB - PURPOSE: To establish baseline and variability of oxygen tension (PO(2)) measurements in the choroid, retinal arteries, capillaries, and veins of spontaneously breathing anesthetized rats and determine the effect of a moderate surgical procedure on the chorioretinal PO(2). METHODS: Our previously established optical section phosphorescence imaging technique was utilized to measure PO(2) in the chorioretinal vasculatures. Imaging was performed in 29 spontaneously breathing rats under ketamine/xylazine anesthesia. In 7 rats, blood was drawn using a surgically implanted femoral arterial catheter and analyzed to determine the systemic arterial PO(2). The PO(2) measurements in 22 rats without surgery (group 1) and 7 surgically instrumented rats (group 2) were statistically compared. The intrasubject variability was calculated by the average standard deviation (SD) of repeated measurements. RESULTS: The average systemic arterial PO(2) was 52 +/- 7 mm Hg (mean +/- SD) in group 2. In group 1, the average PO(2) measurements in the choroid, retinal arteries, capillaries, and veins were 50 +/- 11, 40 +/- 5, 39 +/- 6, and 30 +/- 5 mm Hg, respectively. No statistically significant PO(2) differences in any of the chorioretinal vasculatures were found between the two groups (p > 0.4). The intrasubject variability was 3 mm Hg in the choroid, retinal arteries, capillaries, and veins. CONCLUSIONS: Chorioretinal PO(2) measurements in spontaneously breathing anesthetized rats have a relatively low variability, indicating that PO(2) changes due to various physiological alterations can be reliably assessed. PMID- 17284938 TI - VEGF-targeted RNA interference suppresses angiogenesis and tumor growth of retinoblastoma. AB - Vascular endothelial growth factor (VEGF) is one of the most important angiogenic growth factors for tumor angiogenesis which has been verified to be involved in neovascularization of retinoblastoma. Here, we sought to explore whether RNA interference (RNAi) targeting VEGF could inhibit retinoblastoma angiogenesis and tumor growth. Stable transfection of the two human retinoblastoma cell lines SO RB50 and HXO-RB44 with VEGF-targeted small interfering RNA (siRNA) expression plasmid significantly inhibited VEGF expression determined by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay and Western blot, whereas the control transfection showed no effects. The chemically synthesized VEGF siRNA dramatically suppressed tumor angiogenesis (CD34 immunohistochemistry) and tumor growth in the SO-RB50 subcutaneous xenograft model. Significant downregulation of VEGF expression both on messenger RNA and protein levels in VEGF-siRNA-treated SO-RB50 subcutaneous xenograft was confirmed by real-time PCR and Western blot compared to control. Our data demonstrate the suppression function on angiogenesis and tumor growth of retinoblastoma by VEGF targeted RNAi. This novel therapeutic strategy promises to play a part in the clinical management of retinoblastoma. PMID- 17284939 TI - Intravitreal bevacizumab for filtering surgery. AB - BACKGROUND: It was the aim of this study to report on the intravitreal use of bevacizumab as antiproliferative agent in combination with filtering surgery. METHODS: The clinical interventional case series study included 2 patients (2 eyes) who underwent standard antiglaucomatous penetrating filtering surgery combined with an intravitreal application of 1.5 mg bevacizumab. The intraocular pressure was elevated due to an intravitreal triamcinolone injection as treatment of exudative age-related macular degeneration (patient No. 1) or due to neovascular glaucoma (patient No. 2) after an ischemic retinal branch vein occlusion. RESULTS: At 4 and 12 weeks after surgery, intraocular pressure was reduced in both patients to 10 and 14 mm Hg with functioning filtering blebs. CONCLUSIONS: Intravitreal bevacizumab may potentially be helpful as addition to antiglaucomatous filtering surgery, particularly in neovascular glaucoma. PMID- 17284940 TI - What is important for ultrasound evaluation of occult metastatic lymph nodes in laryngeal cancer: size, shape, vascularity or cytological findings? AB - The assessment of the status of the cervical lymph nodes in patients with a squamous cell carcinoma of the head and neck is still one of the most challenging diagnostic problems. We evaluated ultrasonography criteria with respect to their value for comparative determination of occult metastatic lymph nodes in laryngeal carcinoma. A prospective study was performed in 60 patients with laryngeal squamous cell carcinoma without enlarged neck nodes on CT scan. We used recommended sonography criteria for size, shape and vascularity for distinguishing metastatic and nonmetastatic nodes preoperatively and compared them with cytological and histopathological investigations. Fifty-two of 144 lymph nodes were involved with metastasis on histopathological examination. Respective values for ultrasound-guided fine needle aspiration cytology (USg FNAC) showed high sensitivity, specificity, positive and negative predictive values and accuracy (92, 100, 100, 96, and 97%, respectively). The size, shape and vascularity showed significantly lower values of these statistic parameters. USg FNAC is useful for preoperative evaluation of the neck, as the most reliable, inexpensive and easily available method. It is essential for diagnosis, staging and therapy choices. PMID- 17284942 TI - Implementing glucose control protocols in critically ill patients. PMID- 17284941 TI - Adjustment disorders as stress response syndromes: a new diagnostic concept and its exploration in a medical sample. AB - OBJECTIVE: Adjustment disorders (AD) are an ill-defined category in the present diagnostic nomenclature. We propose a new diagnostic model that describes AD as particular forms of stress response syndrome, in which intrusions, avoidance of reminders and failure to adapt are the central processes and symptoms. In line with the existing classification, the description of AD subtypes is included. Backgrounds on existing psychopathological models of stress response disorders are outlined. METHODS: Data from a clinical sample of patients with an automatic implantable cardioverter defibrillator (n = 160, mean age 63 years, 90% males) are investigated. RESULTS: The items tapping the individual symptoms meet psychometric requirements for diagnostic applications. The diagnostic algorithm chosen indicates a 17% prevalence of AD in the sample. The subtype most commonly diagnosed is AD with mixed emotional features (41%). In a subsample, diagnostic sensitivity was 0.58 and specificity 0.81 in relation to traditional AD cases diagnosed by the Structured Clinical Interview for DSM-IV. By applying the most strongly conservative exclusion rule analogous to the Structured Clinical Interview for DSM-IV, the AD prevalence was reduced to 9%. CONCLUSION: The new AD concept is theory driven and shows methodological soundness. Its application to further samples is recommended. PMID- 17284943 TI - True collaboration: envisioning new ways of working together. PMID- 17284944 TI - Powered by insight: pediatric intensive care nursing. PMID- 17284945 TI - Building trustworthy relationships with critically ill patients and families. AB - A difficult case study involving repeated health crises and irreversible organ dysfunction illustrates the challenges critical care professionals face in caring for patients and their families. In such cases, trust is especially fragile, and coexists with its counterpart, betrayal. The Reina Trust & Betrayal Model defines 3 types of Transactional Trust. The first, Competence Trust, or the Trust of Capability, requires that clinicians practice humility, engage in inquiry, honor the patient's choices, and express compassion. The second, Contractual Trust, or the Trust of Character, demands that clinicians keep agreements, manage expectations, establish boundaries, and encourage mutually serving expectations. The third, Communication Trust, or the Trust of Disclosure, must be rooted in respect and based on truth-telling. Particularly in life-and-death situations, communication requires honesty and clarity. Each type of trust involves specific behaviors that build trust and can guide critical care professionals as they interact with patients and their families. PMID- 17284946 TI - Diarrhea: applying research to bedside practice. AB - Diarrhea is one of many symptoms that may complicate the hospitalization of a critically ill patient. Diarrhea is caused by a variety of etiologies; identifying the etiology aids in the appropriate selection of interventions. Care of the patient with diarrhea should be guided by the evidence and best practices available in the literature. This article defines and describes diarrhea and its pathophysiology. An evidence-based plan of care for the assessment, planning, intervention, and evaluation of the patient with diarrhea is presented, using levels of recommendation based on the strength of the available evidence. A case study is presented to illustrate application to clinical practice. Commentary about the case is provided to review salient points of care. PMID- 17284949 TI - Nausea and vomiting: applying research to bedside practice. AB - Nausea and vomiting are commonly seen in the critically ill patient. While these symptoms are not often the cause for admission to critical care, they complicate and may extend the length of stay as well as the patient's feelings about his or her hospitalization. As with all care provided in critical care, we should strive to implement interventions supported by evidence whenever possible. The article includes definitions, a general description, and the pathophysiology of nausea and vomiting. As well, an evidence-based plan of care for the assessment, planning, intervention, and evaluation of the patient with nausea and vomiting is outlined, using levels of recommendation based on the strength of available evidence. A case study is presented to allow for clinical application: case study commentary reviews the salient points of care. PMID- 17284951 TI - Fever: applying research to bedside practice. AB - Fever occurs frequently in critically ill patients and requires knowledgeable assessment and treatment by critical care nurses. Fever can result from infection or inflammation and should be differentiated from simple hyperthermia. Although temperature measurement and fever management are not often priorities in the management of a critically ill patient, the physiologic consequences of fever may affect patient morbidity. This article defines and describes fever and its pathophysiology. An evidence-based plan of care for the assessment, planning, intervention, and evaluation of the patient with fever is outlined, using levels of recommendation based on the strength of the available evidence. A case study is presented to illustrate application to clinical practice. Commentary about the case is provided to review the salient points of care. PMID- 17284952 TI - Show me the guidelines! PMID- 17284953 TI - Tools for teaching arrhythmias: wide QRS beats and rhythms--part II, QRS morphology clues. PMID- 17284947 TI - Dyspnea: applying research to bedside practice. AB - Dyspnea is a common symptom in patients with acute and chronic critical illness as well as in patients receiving palliative care. While dyspnea can be found in a variety of clinical arenas and across many specialties, the mechanisms that cause dyspnea are similar. Although not often the cause for admission to critical care, it may complicate and extend length of stay. This article defines and describes dyspnea and its pathophysiology. Critical care nurses should strive to implement interventions supported by evidence whenever possible. An evidence-based plan of care for the assessment, planning, intervention, and evaluation of the patient with dyspnea is outlined, using levels of recommendation based on the strength of available evidence. Two case studies are presented to illustrate its application to clinical practice. PMID- 17284954 TI - Histological evaluation of acute mucocutaneous graft-versus-host disease in nonmyeloablative hematologic stem cell transplants with an observation predicting an increased risk of progression to chronic graft-versus-host disease. AB - The incorporation of nonmyeloablative conditioning prior to the transplantation of allogeneic hematopoietic cells has emerged as an alternative to myeloablative chemo- and/or radiotherapy for the treatment of hematologic malignancies. Graft versus-host disease (GVHD) remains a significant complication of both types of hematopoietic cell transplantation (HCT). The clinical phenomenon of late-onset (>100 days after HCT) acute GVHD recently has been described following nonmyeloablative allogeneic transplantation (NMAT); however, there has been no detailed histologic description of acute GVHD in this setting. We sought to characterize the histopathologic features of acute GVHD following NMAT. The clinical and pathologic features of 20 patients with acute GVHD following NMAT over a three-year period were reviewed. Late-onset acute GVHD was diagnosed in 10 of 20 patients with a mean onset of 109.8 days (range 8-410 days); eight (40%) of these subjects with acute GVHD also had concomitant histologic features of chronic lichenoid chronic GVHD. Cases with "composite" histologic features were more likely to progress to fully developed chronic GVHD compared to those without this finding (87.5% vs 25%, P < 0.01). These findings support the existence of late-occurring mucocutaneous GVHD after NMAT and define a strong clinical/laboratory predictor for the subsequent development of chronic GVHD. Patients with composite skin GVHD may benefit from an earlier, more aggressive immunosuppressive interventional strategy. PMID- 17284955 TI - Expression of androgen receptor by fibroepithelioma of Pinkus: evidence supporting classification as a basal cell carcinoma variant? AB - The classification of fibroepithelioma of Pinkus as basal cell carcinoma or trichoblastoma remains controversial. Immunohistochemical stains for androgen receptor may be useful in differentiating basal cell carcinoma from trichoepithelioma or trichoblastoma. We studied androgen receptor expression in 13 fibroepitheliomas of Pinkus, 11 basal cell carcinomas, 12 trichoepitheliomas, and 3 trichoblastomas. Androgen receptor expression was present in 77% (10/13) of fibroepitheliomas of Pinkus, 73% (8/11) of basal cell carcinomas, 17% (2/12) of trichoepitheliomas, and 0% (0/3) of trichoblastomas. Androgen receptor expression was significantly higher in fibroepitheliomas of Pinkus compared with trichoepitheliomas and trichoblastomas (P = .0007), but not basal cell carcinoma (P = 1.00). Tumor-associated Merkel cells, a feature of benign follicular tumors, was identified by cytokeratin 20 stains. Merkel cells were identified in 85% (11/13) of fibroepitheliomas of Pinkus, 27% (3/11) of basal cell carcinoma cases, and 73% (11/15) of benign follicular tumors. Cytokeratin 20 expression was significantly higher in fibroepithelioma of Pinkus and benign follicular tumors compared with basal cell carcinomas (P = 0.0111 and P = 0.025, respectively). No significant difference was found between fibroepitheliomas of Pinkus and trichoepitheliomas and trichoblastomas (P = 1.00). Similar to basal cell carcinomas, fibroepitheliomas of Pinkus express androgen receptors, potentially supporting classification as a basal cell carcinoma. Conversely, fibroepithelioma of Pinkus demonstrates retention of Merkel cells, a feature of benign follicular tumors. Immunophenotypic evidence for the classification of fibroepithelioma of Pinkus remains inconclusive. In small, partial biopsy specimens, coexpression of androgen receptor and cytokeratin 20 may aid in the diagnosis of fibroepithelioma of Pinkus. PMID- 17284956 TI - Epidermodysplasia verruciformis and cutaneous human papillomavirus DNA, but not genital human papillomavirus DNAs, are frequently detected in vulvar and vaginal melanoma. AB - Vulvovaginal melanomas are rare and their etiology is unknown. Genital mucosal human papillomavirus (HPV) 16 has been identified in both cutaneous and mucosal melanoma, suggesting that it might play a role in the pathogenesis or progression of melanoma. In this study, we investigated the prevalence of HPV DNA by using a broad spectrum of degenerate and type-specific primers for genital-mucosal, epidermodysplasia verruciformis-associated (EV), and cutaneous HPV types in 6 vulvar and 3 vaginal melanomas. The patients were mostly postmenopausal women (8/9), had a mean age of 67 years (range, 44-85 years), and had mucosal lentiginous (7) or nodular (2) melanomas. In the adjacent skin/mucosa, mucosal melanosis was found in 5, lichen sclerosus or a lichenoid mucositis in 4, and blue nevi in 2 women. With nested polymerase chain reaction techniques followed by direct sequencing, HPV DNA was identified in 6 of 9 (67%) melanomas; these were either cutaneous (HPV 3) (4/9) or epidermodysplasia verruciformis-associated types (HPV 38, Z95969, AJ00151) (4/9). Epidermodysplasia verruciformis-associated HPV (type 15) was found solely in 1/10 (10%) normal vulvar controls. Genital mucosal HPV types were not detected either by degenerate nested polymerase chain reaction or type-specific probes for HPV 16. We propose that the above findings are not coincidental but may represent a molecular record of HPV involvement in pathogenesis or progression of melanoma, which is consistent with the strong but poorly defined association of cutaneous HPV types with nonmelanoma skin cancers. The theory that HPV may act as a cofactor in melanoma development deserves further clinical and experimental investigations. PMID- 17284957 TI - Cutaneous immunoreactivity of D2-40 antibody beyond the lymphatics. AB - Recent research suggests that the D2-40 monoclonal antibody recognizes the 40,000 Da O-linked sialoglycoprotein podoplanin. Podoplanin not only is highly expressed in lymphatic endothelium but also in other cell types, including sebaceous carcinoma cells. Using the D2-40 antibody, our purpose was to evaluate expression of podoplanin in sebaceous glands of normal skin. Twenty-four formalin-fixed, paraffin-embedded normal skin specimens (10 from scalp and 14 from cheeks) were immunostained using the D2-40 mouse monoclonal antibody. Strong immunostaining with D2-40 antibody was observed at the periphery of sebaceous glands and in skin lymphatic endothelium of all specimens, demonstrating that podoplanin is expressed in sebaceous glands of normal skin. PMID- 17284958 TI - HMB-45 and Melan-A are useful in the differential diagnosis between granular cell tumor and malignant melanoma. AB - Granular cell tumors (GCTs), especially if atypical or malignant, may share cytomorphologic and architectural features with malignant melanoma, when the latter shows granular cell change. In many cases, these neoplasms can be differentiated from each other on histologic grounds, but distinction may sometimes be challenging. By immunohistochemistry, both tumors are strongly positive for S-100 protein and frequently express other nonspecific markers such as CD68, NSE, and NKIC3. In the current study, we reviewed 60 cases of conventional cutaneous, mucosal, and visceral GCT and studied the use of immunoperoxidase staining for the differential diagnosis between malignant melanoma and GCT. Immunohistochemical stains for S-100 protein, A, HMB-45, and microphthalmia transcription factor (MITF) were performed in all cases. All of the tumors were positive for S-100 protein. MITF immunostaining was diffusely positive in 53 (88%) cases, focally positive in three (5%) cases, and negative in four (7%). Fifty-seven (95%) tumors were negative for Melan-A, one case was focally positive, and two cases showed rare positive tumor cells. None of the tumors expressed HMB-45. In conclusion, GCT and malignant melanoma can be reliably differentiated on the basis of immunohistochemical stains in the majority of cases. Although not always positive in malignant melanoma, in this context, HMB-45 expression seems to be 100% specific for the diagnosis of melanoma. Melan-A is slightly less specific, with rare cases of GCT showing focal positivity. MITF is not useful in this differential-93% of the GCTs in our series showed nuclear reactivity for this marker. The latter finding highlights the limited specificity of this antibody in the diagnosis of melanocytic tumors. PMID- 17284959 TI - Squamous eddies in irritated seborrheic keratosis. AB - Seborrheic keratosis is related to the intraepidermal hair follicle in its morphogenesis. Squamous eddies in irritated seborrheic keratosis (ISK) are known to develop by focal maturation of basaloid cells, but the significance of squamous eddies is not understood. The purpose of this study was to elucidate the nature of squamous eddies in ISK. Serial sections of paraffin blocks of 20 cases of ISK were examined. We tracked each squamous eddy through the serial sections to observe the different shapes and positions of the same squamous eddy. In 4 cases, squamous eddies revealed hair shafts at their centers in different sections. In 14 cases, squamous eddies contained acrotrichial canals. In 13 cases, squamous eddies were connected to keratotic invaginations we thought to be follicular infundibula. Eighteen of the 20 cases of ISK showed at least 1 of the morphological features of intraepidermal hair follicle structures. We have found that the squamous eddies of ISK are anatomically related to acrotrichia. PMID- 17284960 TI - Cutaneous vasculitis update: neutrophilic muscular vessel and eosinophilic, granulomatous, and lymphocytic vasculitis syndromes. AB - Most biopsies of cutaneous vasculitis will exhibit a small vessel neutrophilic vasculitis [leukocytoclastic vasculitis (LCV)] that is associated with immune complexes on direct immunofluorescence examination or, less commonly, antineutrophilic cytoplasmic antibodies (ANCA) by indirect immunofluorescence testing. Is in uncommon for skin biopsy to reveal solely a neutrophilic arteritis signifying the presence of cutaneous polyarteritis nodosa or, if accompanied by significant lobular panniculitis, nodular vasculitis/erythema induratum. In other cases, cutaneous vascular damage (fibrinoid necrosis, muscular vessel wall disruption, or endarteritis obliterans) will be mediated by a nonneutrophilic inflammatory infiltrate. Eosinophilic vasculitis can be a primary (idiopathic) process that overlaps with hypereosinophilic syndrome, or it can be a secondary vasculitis associated with connective tissue disease or parasite infestation. Authentic cutaneous granulomatous vasculitis (versus vasculitis with extravascular granulomas) can represent a cutaneous manifestation of giant cell arteritis, an eruption secondary to systemic disease such as Crohn's disease or sarcoidosis, or a localized disorder, often a post-herpes zoster (HZ) phenomenon. Lymphocytic vasculitis is a histologic reaction pattern that correlates with broad clinical differential diagnosis, which includes connective tissue disease - mostly systemic lupus erythematosus (SLE), endothelial infection by Rickettsia and viruses, idiopathic lichenoid dermatoses such as perniosis or ulcerative necrotic Mucha-Habermann disease, and angiocentric cutaneous T-cell lymphomas. Skin biopsy extending into the subcutis, identifying the dominant inflammatory cell and caliber of vessels affected, extravascular histologic clues such as presence of lichenoid dermatitis or panniculitis, and correlation with clinical data allows for accurate diagnosis of these uncommon vasculitic entities. PMID- 17284961 TI - Cutaneous pseudovasculitis. AB - Cutaneous pseudovasculitis represents a heterogeneous collection of disorders that are capable of simulating cutaneous vasculitis and can be broadly classified into diseases that produce hemorrhage (petechiae, purpura, and ecchymoses) or vessel occlusion with resultant livedo, cyanosis, ulcers, digital necrosis, and/or gangrene. Overlap is not uncommon, but if present, one mechanism dominates. Hemorrhagic pseudovasculitis is due to vessel wall dysfunction (incompetence), which can be related to diverse factors that include vessel wall deposition of metabolic substances (amyloid, calcium), nutritional deficiencies (scurvy), nonvasculitic inflammatory purpura (pigmented purpuric dermatitis, arthropod, viral and drug reactions), degeneration of the vessel wall and supporting stroma (senile/solar purpura), direct vessel wall invasion of infective organisms, coagulation-fibrinolytic disorders (eg, thrombocytopenia), and vessel wall trauma. Cyanotic-infarctive pseudovasculitis is due vaso occlusion by emboli, thrombi, or fibrointimal hyperplasia (endarteritis obliterans) and includes varied conditions such as purpura fulminans, Coumadin necrosis, antiphospholipid antibody syndrome, cardiac myxoma, cholesterol embolization, calciphylaxis, and radiation arteritis. Delayed and inappropriate diagnosis of pseudovasculitis leads to incorrect management and exposure to potentially deleterious treatment modalities such as corticosteroids and cytotoxic agents. The diagnosis of a pseudovasculitic disorder requires a high index of suspicion and should always be part of the differential diagnosis of vasculitis. Skin biopsy is a crucial step in differentiating pseudovasculitis from authentic vasculitis; absence of histologic evidence of vasculitis, particularly after multiple biopsies, should direct evaluation and diagnosis towards pseudovasculitis. PMID- 17284963 TI - CD4+ CD56+ hematodermic neoplasm. AB - We report a case of a 75-year-old man with a cutaneous CD4+CD56+ hematodermic neoplasm. CD4+CD56+ hematodermic neoplasms are rare and commonly present as cutaneous lesions. This is an important diagnosis in the differential diagnosis of cutaneous hematologic malignancies because of the extremely poor prognosis. PMID- 17284962 TI - Plexiform epithelioid schwannoma: a case report. AB - Epithelioid schwannoma is rare but may pose a challenge in histopathologic diagnosis. In the present report, we describe a plexiform variant of epithelioid schwannoma in the skin of the breast of a 47-year-old woman. PMID- 17284964 TI - Oral-cutaneous CD4-positive T-cell lymphoma: a study of two patients. AB - We describe two slowly progressive cases of T-cell lymphoma that involved both acral skin and oral cavity. One patient presented with a tongue nodule, completely responded to chemotherapy and then developed recurrent lymphoma involving tongue and skin a few months later that also responded to therapy. The second patient presented with a skin nodule that spontaneously resolved without therapy, and subsequently recurred in tongue and skin a few years later. In both cases, the neoplasms were composed of atypical lymphoid cells with epidermotropism and were of T-helper cell lineage (CD4+). The initial lesions were also negative for CD30. Identical T-cell receptor gene rearrangements were detected in the initial and recurrent lesions of one case. Although these neoplasms were classified as unspecified peripheral T-cell lymphoma because of the unusual distribution of disease, both cases also had histopathologic features of mycosis fungoides. These cases are strikingly similar, and may represent an unusual clinicopathologic type of T-cell lymphoma that can hone to cutaneous and oral mucosal sites with a slowly progressive natural history. PMID- 17284965 TI - Fatal genital verrucous carcinoma. AB - A rare, fatal case of verrucous carcinoma on the labia majora of a 65-year-old woman is presented. Histopathologically, the neoplasm was repeatedly diagnosed as a verruca over the course of many years. A diagnosis of verrucous carcinoma was rendered only after the documentation of lymph node metastasis. Although most cases of verrucous carcinoma have a favorable prognosis, this case illustrates that verrucous carcinoma can metastasize even when the neoplasm is superficially situated and the histopathologic findings are subtle. PMID- 17284966 TI - An unusual case of livedoid and necrotic lesions in a drug addict. AB - Skin biopsies were performed in a patient with livedoid and necrotic lesions of the forearm. Periodic acid-Schiff-stained and birefringent Maltese cross patterned foreign bodies were observed in capillary vessels. It was consistent with the diagnosis of intra-arterial injections of a substance containing corn starch. This finding confirmed the clinical diagnosis of intra-arterial injection of solubilized tablets of buprenorphine. This case constitutes a rare clinical presentation of foreign bodies injections in a drug addict. PMID- 17284967 TI - A carcinoma with features of porocarcinoma, dermal ductular carcinoma, and squamous cell carcinoma in situ. AB - We report the case of a 69-year-old Japanese woman with an extraordinary carcinoma on her back. The tumor had three different histologic components including porocarcinoma, dermal ductular carcinoma, and an area resembling squamous cell carcinoma in situ (SCCIS). Sweat gland tumors (SGTs) are known to have a wide spectrum of pathologic appearances and variable grades of differentiation. This report expands the spectrum of reported combinations. PMID- 17284968 TI - Trichoblastic sarcoma: a high-grade stromal tumor arising in trichoblastoma. AB - We report a case of primary sarcoma of the skin with a biphasic histological pattern, being composed of areas of mixed mesenchymal-epithelial cell proliferation and areas of purely sarcomatous growth. The tumor occurred in the posterior cervical region of a 93-year-old man, and its history was marked by sudden, rapid enlargement after many years of stable duration. The excised lesion was about 4 cm in diameter, had a firm consistency and was covered by intact skin. Histological examination showed a multifocal proliferation of follicular germinative cells arranged in corymbiform and petaloid shapes with an overall retiform growth pattern. Epithelial cords and strands were composed of cytologically uniform cells with bland nuclear features and were surrounded by a prominent, fibroblast-rich stroma reminiscent of a perifollicular sheath. In many areas of the tumor the stroma showed abrupt transition into a pleomorphic proliferation of large sarcomatous cells with frequent and often atypical mitoses. Multinucleated neoplastic cells infiltrated the epithelial structures to cause their partial or total obliteration in many fields of the lesion. Immunohistochemically, the epithelial cells displayed expression of various keratins, with a particularly intense staining for 34betaE12, and were partly positive for the CD10 antigen. A strong immunostaining for this antigen was also observed in malignant-appearing stromal areas, where no expression of cytokeratins was detected. Moreover, nuclear positivity for p53 protein was seen in sarcomatous cells, whereas it resulted in total lack of epithelial elements. Our case emphasizes that high-grade sarcoma may occur in the spectrum of trichoblastic tumors and that it may share some features of other noncutaneous biphasic neoplasms, such as mammary cystosarcoma phyllodes. PMID- 17284969 TI - Granular cell atypical fibroxanthoma: report of two cases. AB - Two cases of an uncommon histopathological variant of atypical fibroxanthoma (AFX) are described. Even though both lesions presented as clinically conventional atypical fibroxanthoma, histopathology disclosed a neoplasm composed of cells with granular change that was negative for S100 staining, and showed prominent pleomorphism, severe nuclear atypia, and a high mitotic index. Degenerative change may explain the granular phenotype in these two cases of AFX. The differential diagnosis with primitive nonneural granular cell tumor is discussed. PMID- 17284970 TI - Malignant blue nevus: case report of a Japanese man with a distant cutaneous metastasis. AB - We report a 55-year-old Japanese patient with a malignant blue nevus (MBN) on the scalp. The patient had regional lymph nodes metastases at his first visit, and a distant cutaneous metastatic papule appeared on the back 1 year later despite therapeutic intervention. Histology of the primary tumor lacked a junctional component and showed a typically biphasic pattern in the degree of pigmentation similar to a cellular blue nevus (BN). One pattern showed nests of less pigmented, oval-shaped cells with a fairly uniform appearance, and the other pattern showed an aggregation of spindle-shaped cells containing a large amount of melanin pigment intermingled with heavily pigmented melanophages. Histology of metastatic regional lymph nodes also showed a biphasic proliferative pattern of oval-shaped, pale cells and spindle-shaped, richly pigmented cells. A distant cutaneous metastatic papule on the back showed massive proliferation of atypically large, pale, and oval-shaped melanoma cells with heavily pigmented melanophages just beneath the uninvolved epidermis. These histologic features were different from those of metastatic tumor proliferation from conventional melanoma. It seems probable that MBN might maintain a different biological and histopathologic character from conventional melanoma when it grows in metastatic sites. PMID- 17284971 TI - Trichoadenoma associated with an intradermal melanocytic nevus: a combined malformation. AB - Melanocytic nevi have been associated with epidermal hyperplasia, adnexal hyperplasia with follicular and sebaceous differentiation, cysts, and tumors of epidermal or adnexal origin. We report a combined cutaneous hamartoma in a 29 year-old woman that comprised a trichoadenoma within an intradermal melanocytic nevus. Clinical diagnosis was a malignant transformation of a melanocytic nevus. Histopathologically, multiple keratinous cysts together with solid islands or masses of eosinophilic epithelial cells were closely intermingled with the nevus cells. Occasional nests of basaloid cells were present. Although to our knowledge this association has not been previously reported, it is worth considering that trichoadenoma and desmoplastic trichoepithelioma are the two ends of a spectrum of lesions. This combined hamartoma reported herein is important because growth of these lesions could be clinically misinterpreted as malignant transformation of a preexisting lesion. Histologic study will reveal the correct diagnosis in such cases. PMID- 17284972 TI - Cutaneous sarcomatoid B-cell lymphoma. AB - A rare case of a spindle cell (sarcomatoid) B-cell lymphoma is described. The patient, a 48-year-old male, presented with a several month history of an enlarging lesion on the scalp. Although there have been a few recent reports of cutaneous sarcomatoid lymphomas, this case is especially unusual because it presented as a scarlike plaque rather than a tumor and microscopically exhibited a prominent myxoid matrix. Given these features, the lesion was initially interpreted as an atypical fibromucinosis. The differential diagnosis included fibromucinous lesion consistent with variant of lichen myxedematosus, spindle cell carcinoma, spindle cell melanoma, atypical fibroxanthoma, and atypical smooth muscle tumors. Initial immunoperoxidase studies demonstrated negative staining for CD68, factor XIIIa, CD57, cytokeratin(AE1/AE3), S100, EMA, and vimentin, essentially ruling out the previously mentioned neoplasms. Subsequently, strong positive staining for LCA(CD45RB) and CD20 was demonstrated characteristic of a B-cell lymphoma. The patient underwent local radiotherapy with complete resolution. Although all variants of cutaneous sarcomatoid B-cell lymphomas are rare, it is imperative to consider them in the differential diagnosis of otherwise difficult to categorize spindle cell proliferations. This includes neoplasms and, based on the current case, fibromucinoses as well. PMID- 17284973 TI - Juvenile hyaline fibromatosis and infantile systemic hyalinosis overlap associated with a novel mutation in capillary morphogenesis protein-2 gene. AB - Juvenile hyaline fibromatosis (JHF) is a rare condition of childhood characterized by deposition of an amorphous substance of unclear nature in the dermis and subcutaneous tissues. The clinical picture includes painful skin lesions, leading to impairment of movements and severe disabilities. The allelic disease, infantile systemic hyalinosis (ISH), clinically overlaps with JHF but shows a worse picture with visceral involvement. Recently, germline mutations in the capillary morphogenesis gene-2 (CMG2) were found to be responsible for both diseases. Here, we present a case with classical clinicopathologic findings of JHF and features of ISH, and we describe a novel mutation in CMG2. PMID- 17284974 TI - Incidental findings in negative sentinel lymph nodes of patients with malignant melanoma: report of three cases. AB - We present three cases of benign SLN that were clinically suspicious for involvement by metastatic melanoma and where found to be involved with other diseases or deposits previously unknown. PMID- 17284975 TI - Disseminated pustules in a patient who had received a heart transplant. PMID- 17284976 TI - Peculiar zone of the distal nail unit: the nail isthmus. PMID- 17284977 TI - The many faces of alpha-herpesviridae infections. PMID- 17284980 TI - Hybrid palliation in hypoplastic left heart syndrome. AB - PURPOSE OF REVIEW: Despite progressive improvement in surgical results, hypoplastic left heart syndrome remains one of the congenital heart abnormalities with the greatest morbidity and mortality. Hybrid approaches to management, combining surgical and interventional catheterization procedures, have been introduced to minimize exposure to cardiopulmonary bypass, and improve outcomes for these high-risk infants. RECENT FINDINGS: First-stage palliation of hypoplastic left heart syndrome has been performed as a hybrid procedure combining surgical pulmonary artery banding with catheterization stenting of the ductus arteriosus and balloon atrial septostomy, especially in high-risk patients. Additionally, several centers have performed second-stage palliation - bidirectional Glenn or hemi-Fontan procedures - in a manner that allows the subsequent 'Fontan' procedure to be completed in the catheterization laboratory with a covered stent. SUMMARY: These innovative procedures offer the potential of an alternative management strategy for hypoplastic left heart syndrome. They have been applied to a very limited number of patients and long-term results are not available. Their role in management of hypoplastic left heart syndrome remains to be defined, especially as results of conventional surgical management continue to improve. PMID- 17284981 TI - Stage I palliation for hypoplastic left heart syndrome: Norwood versus Sano modification. AB - PURPOSE OF REVIEW: Advancements in surgical technique and perioperative care have significantly improved the survival of infants born with hypoplastic left heart syndrome. A recent modification to the Norwood procedure is being adopted by many centers to improve postoperative hemodynamic stability and survival to stage II palliation. The late effects of this modification, however, are speculated and have not been investigated. RECENT FINDINGS: Center-specific improved short-term outcomes have been reported in a few small, nonrandomized studies of a new approach to the Norwood procedure, which utilizes a right ventricle to pulmonary artery shunt or Sano modification to provide pulmonary blood flow rather than the standard modified Blalock-Taussig shunt. SUMMARY: The classic Norwood procedure and Sano modification each have specific advantages and disadvantages in both the short and long term. Data comparing the two techniques are nonrandomized, contradictory, and utilize historical controls. The optimal shunt to improve survival to the second-stage palliation is unknown. A multicenter randomized clinical trial comparing the Sano with the modified Blalock-Taussig shunt in hypoplastic left heart syndrome or variants is currently in progress and should hopefully provide future guidelines for shunt selection based on clinical presentation. PMID- 17284982 TI - Pathophysiology and diagnosis of allograft rejection in pediatric heart transplantation. AB - PURPOSE OF REVIEW: Attempts at improving diagnostic monitoring of allograft rejection continue at a steady pace. The main issue remains whether these methods will replace the standard method of tissue histology from endomyocardial biopsy. RECENT FINDINGS: The aim in the development of novel techniques to diagnose rejection is the application of noninvasive methods. These range from echocardiography, biomarkers, and genomic profiling to more sensitive antibody detection systems. No single method has the accuracy to be a stand-alone test. Methods of assessing graft dysfunction alone may not be accurate enough in this population. Nonetheless, these and other clinical descriptive studies help us better understand the rejection process in pediatric recipients. SUMMARY: Solid organ transplantation creates the ideal medium where basic science meets clinical science. Clinical cardiology continues to improve on ways to assess organ dysfunction, but to correlate these methods to early graft rejection, immunobiologic techniques will probably need to be incorporated. PMID- 17284983 TI - Pediatric cardiac resynchronization pacing therapy. AB - PURPOSE OF REVIEW: Advances in pacemaker lead designs, permitting precise lead implantation at sites other than the ventricular apex, have provoked interest in the utilization of ventricular pacing beyond maintenance of heart rate. Select older adult patients with various cardiomyopathies may improve clinically following alternative site, biventricular and cardiac resynchronization pacing. This report reviews recent applications and directions of these pacing technologies to younger patients with congenital heart defects. RECENT FINDINGS: Acutely, following congenital heart surgery or chronically, studies now indicate that select younger patients may demonstrate physiologic benefits from pacing preselected single ventricular or combined right and left ventricular sites. This may prevent eventual paced myocardial deterioration as well as support and even reverse existing myocardial dysfunction, deferring the need for heart transplantation. SUMMARY: There are limited worldwide pediatric experiences, and, to date, no randomized multicenter studies. It is becoming more evident, however, that as these pacing techniques are used in younger patients, clinical improvements, comparable to older adult patients, even delaying heart transplant, may be anticipated. Since these newer techniques are more complicated and costly than simple pacemaker implantation, future directions will be for multi institutional pediatric studies with clear definition of which pre-implant variables will define physiologic improvement. PMID- 17284984 TI - Aortic valve endocarditis: is there an optimal surgical timing? AB - PURPOSE OF REVIEW: Patients with aortic valve infective endocarditis are likely to undergo surgery during the active phase of the disease. The indication and best timing for surgery, however, are still debated. The present review discusses the benefits and risks of early surgery in aortic endocarditis. RECENT FINDINGS: Patients with acute aortic regurgitation and clinical or echocardiographic signs of poor tolerance require urgent surgery. Other indications for early surgery include severe perivalvular involvement and high embolic risk. Echocardiography plays an important role in the assessment of embolic risk and helps in choosing the best therapeutic strategy. Several recent studies have identified high-risk subgroups of patients that, without surgery, face poor prognosis. Patients with complicated endocarditis, particularly those with congestive heart failure, will benefit most from surgery. Patients with prosthetic valve endocarditis and cerebral complications represent specific subgroups in which surgical decision is more difficult. SUMMARY: Patients with severe aortic leaflet destruction and congestive heart failure, patients with perivalvular extension or uncontrolled infection, and patients with high embolic risk have poor outcome under medical therapy. Early surgery is necessary in all such patients with 'complicated' endocarditis, unless severe comorbidity is present. PMID- 17284985 TI - Low-flow, low-gradient aortic stenosis: from evaluation to treatment. AB - PURPOSE OF REVIEW: Valve replacement improves symptoms and survival in symptomatic severe aortic stenosis. Low-flow, low-gradient aortic stenosis, however, is an especially challenging subset as valve replacement has a significant risk, and may fail to alleviate symptoms or improve left ventricular function. This article reviews the potential problems in evaluating aortic stenosis severity in low-flow, low-gradient aortic stenosis, the utility of dobutamine challenge to identify patients most likely to benefit from surgery, and the factors predicting patient outcome. RECENT FINDINGS: Low-flow, low gradient aortic stenosis consists of a heterogeneous group of patients with 'true' severe aortic stenosis, in whom afterload mismatch results from a severely stenotic valve; and 'pseudo-severe' aortic stenosis, where the valve is only mildly or moderately stenotic, but appears severe due to limitations in determining disease severity under low-flow conditions. Valve replacement is likely to benefit the former group, but may have little benefit to the latter. Dobutamine challenge can distinguish 'true' and 'pseudo-severe' aortic stenosis, and can evaluate contractile reserve, one of the strongest predictors of patient outcome. Strategies to avoid prosthesis-patient mismatch should be considered to optimize postoperative outcome. SUMMARY: Dobutamine challenge can identify low flow, low-gradient aortic stenosis patients most likely to benefit from valve replacement and provides important prognostic information on the operative risks and long-term outcome. PMID- 17284986 TI - Aortic valve replacement in elderly patients: what are the limits? AB - PURPOSE OF REVIEW: Increased life expectancy has led to a growing elderly population frequently presenting with aortic stenosis. This review focuses on modalities of aortic valve replacement designed to cope with the risks from multiple co-morbidities prevalent in the elderly. RECENT FINDINGS: Cardiac surgery is safe in octogenarians; very low risks are associated with aortic valve replacement. Good short-term and medium-term results are seen with early surgical intervention for aortic stenosis in the relatively asymptomatic patient. The benefits seen with minimally invasive surgery make it more acceptable. A hybrid approach that deploys a drug-eluting stent for concomitant moderate coronary artery disease has shown promising results. An extension of this concept is the percutaneous aortic valve implantation that offers hope to the nonsurgical candidate. A systematic approach of minimally invasive surgery in patients with prior coronary artery bypass grafting minimizes injury to grafts. Bioprosthetic tissue valves are the valves of choice in all the above interventions. SUMMARY: Cardiac surgery is used increasingly for aortic stenosis in elderly patients. Current experiences in minimally invasive and percutaneous approaches have opened the doors to hybrid strategies, which may be the mainstay of treatment for older patients needing aortic valve replacements in the future. PMID- 17284987 TI - Stentless valves for aortic valve replacement: where do we stand? AB - PURPOSE OF REVIEW: Following more than a decade's experience with stentless valves and the development of better profiled stented valves, the article discusses the advantages of stentless valves regarding hemodynamic performance, left ventricular mass regression, durability and survival. RECENT FINDINGS: Recent studies show that stentless valves remain hemodynamically superior compared with modern porcine stented valves. This superiority is, however, rarely reported in comparison with modern pericardial stented valves. In general, patient-prosthesis mismatch is less frequent in stentless vs. stented valves. Recent randomized trials comparing stentless valves and modern stented valves show equivalent left ventricular mass regression at 1 year. At 10 years, stentless valve durability is excellent and comparable with that of stented valves. Recent comparative studies do not confirm the previously reported midterm survival advantages of stentless valves. SUMMARY: Improvement of stented valves has significantly reduced the hemodynamic differences between them and their stentless counterpart. Patients with small aortic annulus, however, should benefit from a stentless valve due to the better expected gradients and lower risk of patient-prosthesis mismatch. Midterm results suggest equivalent durability and survival for both prosthesis types but additional and longer-term trials are necessary to confirm these results. PMID- 17284989 TI - Proliferation signal inhibitors in cardiac transplantation. AB - PURPOSE OF REVIEW: Standard immunosuppression after cardiac transplantation includes a calcineurin inhibitor in combination with mycophenolate mofetil or azathioprine and corticosteroids. These agents have led to excellent outcomes but have shortcomings in terms of efficacy and toxicity. A new class of immunosuppressants, proliferation signal inhibitors, may meet some of these shortcomings. RECENT FINDINGS: The efficacy of the available proliferation signal inhibitors - sirolimus and its derivative everolimus - has been compared with azathioprine in three randomized clinical trials. Sirolimus or everolimus use was associated with lower rates of acute rejection and reduced development of chronic allograft vasculopathy. Sirolimus was not found to be superior to mycophenolate mofetil in a randomized trial. Proliferation signal inhibitors have been reported to be effective in refractory recurrent acute rejection. Nonrandomized studies have demonstrated that proliferation signal inhibitor-based immunosuppression enables recovery from renal dysfunction secondary to calcineurin inhibitor treatment. Proliferation signal inhibitor-based treatment is associated with a lower risk of malignancy than calcineurin inhibitor-based regimens. Proliferation signal inhibitors have significant adverse effects that may limit widespread use. SUMMARY: Proliferation signal inhibitors are important new immunosuppressive agents that have added considerably to the armamentarium allowing further tailored immunosuppression to individualize patient care after heart transplantation. PMID- 17284988 TI - Cellular transplantation: future therapeutic options. AB - PURPOSE OF REVIEW: Cardiac transplantation is a complex undertaking and an imperfect solution to end-stage heart failure. Cellular transplantation has been proposed as an alternative solution; however, clinical trials at present are small and show variable results. The mechanisms behind stem cell therapy have not yet been elucidated. RECENT FINDINGS: Several large trials have been presented that address the question of bone marrow stem cells as therapy for acute myocardial infarction, and also the possible benefits of therapy with granulocyte colony-stimulating factor. Although some trials show a modest improvement in ejection fraction or reduction of infarct size, other trials show no change with treatment. Fewer clinical data are available on the treatment of chronic left ventricular systolic function. Many questions remain such as what cell type to use, dosing, the ideal timing for therapy, and the technique of cell delivery. Finally, further research continues on the cellular milieu, enhancement of cell engraftment, proliferation, and survival. SUMMARY: This review briefly examines the background for stem cell therapy, as well as the larger clinical trials of stem cell therapy for acute myocardial infarction and chronic left ventricular systolic dysfunction, and possible pharmacologic enhancement options. PMID- 17284990 TI - New advances in antirejection therapy. AB - PURPOSE OF REVIEW: The prevention and treatment of rejection have been the major focus of clinical and research studies since the inception of heart transplantation. Recent improvement in survival after transplant has been in large part due to continued advancement in antirejection therapies. RECENT FINDINGS: The combination of steroids/cyclosporine/azathioprine has been widely used since the early 1980s. The last decade has seen the increasing use of the drugs mycophenolate mofetil and tacrolimus. Newer agents such as target of rapamycin protein inhibitors and anti-interleukin-2 inhibitors have come under intense research recently, and may play a significant role in heart transplantation. Further study is required for agents such as rituximab. With the recent introduction of a new grading of cardiac allograft rejection, controversy remains over when rejection should be treated and which agents should be used. SUMMARY: Use of newer proven antirejection drugs has reduced rejection and improved survival after heart transplantation. Rejection and side effects from these drugs are still major problems, however; therefore continued research in this area is required. PMID- 17284991 TI - Tricuspid valve replacement after cardiac transplantation. AB - PURPOSE OF REVIEW: Tricuspid valve regurgitation is the most frequent valvular complication following orthotopic cardiac transplantation. It leads to diminished quality of life and predicts shortened long-term survival. The optimal surgical management of refractory tricuspid valve regurgitation in this setting is unclear. RECENT FINDINGS: Tricuspid valve regurgitation following cardiac transplantation is likely related to accumulated injury from repeated endomyocardial biopsies. Durability of repair in this setting was shown to be suboptimal. Replacement with a bioprosthesis was found to be durable and relieves symptoms of heart failure associated with tricuspid valve regurgitation in the majority of patients. Prophylactic tricuspid valve annuloplasty at transplantation was found to significantly decrease the incidence of early and late tricuspid valve regurgitation; long-term benefits remain unclear. SUMMARY: Results of tricuspid valve repair in the post-cardiac transplant setting are not ideal, and this strategy is better suited to treating functional tricuspid valve regurgitation resulting from annular dilatation. Tricuspid valve replacement with a bioprosthesis is a safe, durable, and effective method of treating tricuspid valve regurgitation following transplantation and allows for future endomyocardial biopsies to be performed. Mechanical valves should be avoided. A randomized controlled trial examining the long-term outcomes of prophylactic tricuspid annuloplasty is warranted. PMID- 17284992 TI - Use of calcium channel blockers and angiotensin-converting enzyme inhibitors after cardiac transplantation. AB - PURPOSE OF REVIEW: Hypertension, dyslipidemia, and diabetes are very common problems following heart transplantation and may contribute to the development and progression of graft coronary artery disease. This article reviews current data on clinical use of angiotensin-converting enzyme inhibitors and calcium channel blockers in patients who have had heart transplants. RECENT FINDINGS: Angiotensin-converting enzyme inhibitors and calcium channel blockers are established therapy for patients with cardiovascular disease. Use of these medications correlates with decreasing cardiovascular morbidity and mortality. SUMMARY: After heart transplantation, hypertension associated with calcineurin inhibitors can be managed effectively with antihypertensive therapy, but it may require use of more than one antihypertensive agent. Calcium channel blockers and angiotensin-converting enzyme inhibitors have been associated with improved outcome measures in graft coronary artery disease. PMID- 17284994 TI - Diagnosis of graft coronary artery disease. AB - PURPOSE OF REVIEW: Graft coronary artery disease is the leading cardiac cause of death in patients who have undergone cardiac transplantation. Due to denervation, classic symptoms of angina are not reliable. Many transplant centers have a protocol of routine annual surveillance cardiac angiography because treatment options are limited, especially with advanced disease. Angiography is an assessment of the arterial lumen, however, and can miss nonfocal disease. This paper reviews invasive and noninvasive diagnostic tools for graft coronary artery disease. Intravascular ultrasound is the most sensitive, but the cost and lack of widespread expertise make it unpopular. Noninvasive techniques have been studied. An ideal test would be sufficiently sensitive to detect disease and allow for prognostic information. Dobutamine echocardiography is the most sensitive noninvasive test but can have a high false-positive rate. It is also not universally available. Exercise nuclear imaging is specific and can be used as a confirmatory test in patients with positive dobutamine echocardiograms. RECENT FINDINGS: Computed tomographic imaging and cardiac magnetic resonance imaging are exciting new modalities but require further study. SUMMARY: There is no test sensitive and specific enough yet that can be confidently used to replace coronary angiography. PMID- 17284993 TI - Renal protective strategies in heart transplant patients. AB - PURPOSE OF REVIEW: Chronic renal failure associated with long-term calcineurin inhibitor immunosuppression is a substantial clinical problem in the heart transplant population, compounded by difficulties in identifying patients likely to develop renal dysfunction. Several approaches, however, have been developed or are being investigated to preserve renal function in heart transplant patients. RECENT FINDINGS: Approaches to identify patients with an increased risk of developing renal dysfunction are being refined, and improved calcineurin inhibitor monitoring strategies are being investigated. Novel immunosuppressive regimens including mycophenolate mofetil and/or rapamycin that lack nephrotoxicity promise new therapeutic strategies with the efficacy of calcineurin inhibitor-based combinations. Temporary ('holiday') or permanent ('retirement') calcineurin inhibitor replacement with interleukin-2 receptor monoclonal antibodies has the potential to halt progressive renal dysfunction. Finally, emerging data on the renal protection afforded by angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, either singly or in combination, provide another avenue of investigation. SUMMARY: Several strategies have demonstrated their potential to preserve or improve renal function in heart transplant patients in small studies. Large randomized controlled trials are necessary to determine the optimal strategies to prevent rejection while preserving renal function in the long-term management of heart transplant patients. PMID- 17284995 TI - Determinants of brain natriuretic peptide gene expression and secretion in acute cardiac allograft rejection. AB - PURPOSE OF REVIEW: Circulating levels of the cardiac hormone brain natriuretic peptide in heart transplant patients may increase before and during an acute rejection episode. A similar increase in atrial natriuretic factor does not occur. This article reviews the possible significance of these findings. RECENT FINDINGS: During acute cardiac allograft rejection episodes, brain natriuretic peptide plasma levels may increase well above baseline values. This increase is not the result of hemodynamic changes because brain natriuretic peptide levels during International Society for Heart and Lung Transplantation grade 3 rejection do not correlate with various hemodynamic parameters, and atrial natriuretic factor levels are not affected. Similar results were observed in experimentally induced autoimmune myocarditis. In-vitro data showed that some proinflammatory cytokines and chemokines are capable of selectively increasing brain natriuretic peptide gene expression and secretion in cardiocyte cultures. SUMMARY: Atrial natriuretic factor and brain natriuretic peptide are usually co-regulated. Findings in heart allograft recipients, in experimentally induced myocarditis, and in vitro suggest that, unlike atrial natriuretic factor, brain natriuretic peptide is uniquely related to inflammation. These findings may translate into biomarkers or therapies for cardiac allograft rejection or myocarditis and may explain the existence of two hormones with nearly identical biologic properties. PMID- 17284996 TI - Bibliography. Current world literature. Pediatrics cardiology. PMID- 17284998 TI - Sources of the very-long-chain unsaturated omega-3 fatty acids: eicosapentaenoic acid and docosahexaenoic acid. AB - PURPOSE OF REVIEW: We assess the toxicological, environmental and economic aspects of sources of fish oil and omega-3 fatty acids (n-3 fatty acids). RECENT FINDINGS: Fish oils are the most common source of the very-long-chain n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid, which have protective and beneficial effects on conditions such as cardiovascular, inflammatory, or neurological diseases. Fish oils can also be potential hazards for human health, because of external pollutants bio-accumulating in fish. Wild and farmed fish are generally both similar in n-3 fatty acid content but may vary in terms of potential toxins. Reports on aquaculture and fish oil production, and other sources of n-3 fatty acids, are reviewed to assess which may be more suitable economically and ecologically for higher fish oil production and availability. SUMMARY: Although today's fish oil production meets demand, it is likely that this will not be able to increase without adversely affecting the world's wild stock of fish. Neither wild nor farmed fish constitute a sustainable source of n 3 fatty acids for supplementation. Solutions may be found through the evolution of the current aquaculture system or the utilization of alternative manufacturing sources for increasing intakes of n-3 fatty acids. PMID- 17284999 TI - Omega-3 fatty acids and cardiovascular disease. AB - PURPOSE OF REVIEW: In the last 2 years in the cardiovascular field eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been investigated in terms of their epidemiology and vascular biology, and in large-scale intervention trials, and incorporated into the guidelines of cardiac societies. EPA and DHA have advanced from scientific research into everyday practice, a development reviewed here. RECENT FINDINGS: EPA and DHA are antiarrhythmic on the supraventricular and ventricular levels, besides having an anti-atherosclerotic effect. Fish rich in EPA and DHA, contaminated with methyl-mercury, appears less protective. Large-scale clinical trials demonstrated that morbidity can be reduced with EPA even in a population already consuming large amounts of EPA and DHA. Therapy with EPA and DHA can be monitored with the omega-3 index, a risk factor for sudden cardiac death. EPA and DHA appear to be cost-saving in the USA, and, as Omacor, are cost-effective in several European countries. SUMMARY: European and American Cardiac Societies incorporated EPA and DHA into recent treatment guidelines for myocardial infarction, prevention of cardiovascular disease, treatment of ventricular arrhythmias and prevention of sudden cardiac death. Physicians need to reduce the burden of cardiovascular disease by advocating EPA and DHA to all patients likely to benefit. PMID- 17285000 TI - Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. AB - PURPOSE OF REVIEW: To summarize recent findings that docosahexaenoate (DHA) is the precursor of stereospecific derivatives with anti-inflammatory and cytoprotective properties. RECENT FINDINGS: The docosahexaenoate-derived mediator neuroprotectin D1 is formed in retinal pigment epithelial cells when confronted with oxidative stress, in the brain during experimental stroke, and in the human brain from Alzheimer's disease patients as well as in human brain cells in culture. Neuroprotectin D1 displays potent anti-inflammatory and neuroprotective bioactivity. SUMMARY: Here, we summarize recent studies demonstrating that in brain ischemia-reperfusion and in retinal pigment epithelial cells exposed to oxidative stress stereospecific docosahexaenoate-oxygenation pathways are activated and lead to the formation of docosanoid messengers. Two docosahexaenoate-oxygenation pathways were identified: the first is responsible for the formation of the messenger neuroprotectin D1 and the second pathway, which is active in the presence of aspirin, leads to the formation of the resolvin-type mediators (17R-DHA). Neuroprotectin D1 induces antiapoptotic, anti inflammatory signaling and is neuroprotective. PMID- 17285001 TI - Free fatty acids and insulin resistance. AB - PURPOSE OF REVIEW: Dysregulation of free fatty acid metabolism is a key event responsible for insulin resistance and type 2 diabetes. According to the glucose fatty acid cycle of Randle, preferential oxidation of free fatty acids over glucose plays a major role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. However, other mechanisms are now described to explain the molecular basis of insulin resistance. RECENT FINDINGS: Recent studies have suggested that local accumulation of fat metabolites such as ceramides, diacylglycerol or acyl-CoA, inside skeletal muscle and liver, may activate a serine kinase cascade leading to defects in insulin signalling and glucose transport. Inflammation and oxidative stress are also potent mechanisms which could lead to a state of insulin resistance. Finally, modulation of transcription by free fatty acids through their binding to peroxisome proliferator-activated receptors could also contribute to impaired glucose metabolism. SUMMARY: The increase in free fatty acid flux resulting from increased lipolysis secondary to adipose-tissue insulin resistance induces or aggravates insulin resistance in liver and muscle through direct or indirect (from triglyceride deposits) generation of metabolites, altering the insulin signalling pathway. Alleviating the excess of free fatty acids is a target for the treatment of insulin resistance. PMID- 17285002 TI - Sphingolipids: major regulators of lipid metabolism. AB - PURPOSE OF REVIEW: Sphingolipids and their metabolites regulate a great variety of cellular processes. Recent findings implicate sphingolipids in the regulation of lipid synthesis, lipoprotein metabolism and the development of atherosclerosis. RECENT FINDINGS: Sphingolipid synthesis correlates with the regulation of the sterol-regulatory element-binding proteins - key transcription factors of genes of lipid metabolism. Inhibition of sphingolipid synthesis decreases synthesis of genes regulated by sterol regulatory element-binding protein, such as the rate-limiting enzymes of fatty acid and cholesterol synthesis as well as fatty-acyl-CoA synthases, important in the synthesis of phospholipids. In animal models, inhibition of sphingolipid synthesis correlates with decreased atherosclerotic lesions and a decreased susceptibility of lipoproteins to aggregate--a key mechanism in the development of the atherosclerotic lesion. The demonstration that ceramide and glucosylceramide (metabolites of sphingolipid synthesis) affect cholesterol efflux and mechanisms that regulate plasma high-density lipoprotein concentrations is further evidence for a role of sphingolipids in the regulation of lipid homeostasis. Direct mechanisms of how sphingolipid synthesis regulates lipid synthesis are currently unknown. The recent identification of key proteins of synthesis and specific transport proteins that regulate sphingolipid synthesis, however, is expected to contribute to the understanding about the interdependent regulation of sphingolipid and lipid metabolism. SUMMARY: Emerging data strongly suggest a role of sphingolipid synthesis in the regulation of transcription factors and regulatory proteins that control cellular lipid homeostasis. PMID- 17285003 TI - Lipases and lipolysis in the human digestive tract: where do we stand? AB - PURPOSE OF REVIEW: The review evaluates current knowledge of the different lipases catalyzing triglyceride lipolysis in the human digestive tract, focusing on their mode of action - information useful for developing strategies to regulate the bioavailability of fatty acid. RECENT FINDINGS: Optimal levels of digestive lipases promote efficient triglyceride lipolysis in healthy humans. Management of fatty acid bioavailability during pancreatic insufficiencies, however, requires enzyme replacement therapy. Such therapy entails gastro protected porcine pancreatic powder, associated with antacid treatment when duodenal pH is too acidic; recently, enteric-coated high-buffered pancrelipase or recombinant gastric lipase have been used. Another promising strategy is to focus on lipid substrate to optimize lipid-water interface properties. Research on obesity treatment focuses on inhibitors. Orlistat is the first inhibitor to be used extensively. Others treatments are in development, including human pancreatic lipase C-terminal, polyphenols, specific proteins and peptides; however, their relevance has not yet been tested in humans. SUMMARY: A better knowledge of lipase structure and mode of action will help the development of new natural inhibitors with fewer secondary effects. More intensive research in protein engineering for recombinant lipase production and in clinical nutrition, together with careful evaluation of patients' individual needs is necessary. PMID- 17285004 TI - Olive oil in parenteral nutrition. AB - PURPOSE OF REVIEW: A lipid emulsion for use in parenteral nutrition containing a significant proportion of olive oil in place of soybean oil (ClinOleic; Baxter, Maurepas, France) is now available. The purpose of this review is to provide background information about the rationale for this emulsion, to collate and synthesize the literature about it, and to highlight recent studies in which it has been used. RECENT FINDINGS: ClinOleic offered significant advantage over soybean oil-based emulsions in terms of glucose metabolism in preterm infants. ClinOleic was recently used for the first time in malnourished haemodialysis, trauma and burn patients and was found to be safe and well tolerated. In burn patients ClinOleic was associated with better liver function. SUMMARY: ClinOleic is safe and well tolerated in preterm infants, and in home parenteral nutrition, haemodialysis, trauma and burn patients and may offer advantages with regard to liver function, oxidative stress and immune function. ClinOleic may offer significant advantage over soybean oil-based emulsions in terms of glucose metabolism in preterm infants. More clinical studies of ClinOleic are required and these should include evaluation of oxidative stress markers and immune function as well as of clinical outcomes. PMID- 17285005 TI - Nutrition support and metabolic control: from evidence-based to systems biology. PMID- 17285006 TI - Practical aspects of implementing tight glucose control in the ICU. AB - PURPOSE OF REVIEW: The outcomes of intervention studies implementing intensive insulin therapy aimed at tight glucose control (TGC) are yet not conclusive. There is concern about an increasing incidence of hypoglycemic episodes. Normoglycemia is not easy to obtain in a 'real-life' ICU setting. To facilitate the implementation of TGC, we review its practical aspects. RECENT FINDINGS: Point-of-care blood gas/glucose analyzers currently present the best trade-off between accuracy and speed. A nurse-driven dynamic scale protocol leads to the most efficacious and safe implementation of TGC. Paper protocols have been published and computerized protocols are a new development. Closed-loop systems are not yet available for clinical use. SUMMARY: Clinicians should take care in selecting both the patient group and target blood glucose level. As long as doubts remain about the potential benefits, it is important to perform TGC in a safe way. This can be done with a nurse-driven protocol, using arterial blood samples measured on a point-of-care blood gas analyzer. Insulin administration should be continuous, and guided by a dynamic scale protocol either on paper or on the computer. Periodical monitoring of performance and incremental modification of the protocol leads to best results. PMID- 17285008 TI - Hyperglycemia in the pediatric intensive care unit. AB - PURPOSE OF REVIEW: Studies on critically ill adults demonstrate the benefits of glycemic control. There is a paucity of data, however, in pediatric intensive care settings. This review summarizes sentinel papers in the adult literature, outlines mechanisms by which hyperglycemia mediates its effects in the critically ill, highlighting those described in pediatrics, and discusses studies that associate hyperglycemia with negative outcome in critically ill children. RECENT FINDINGS: Retrospective studies and prospective cohort studies have linked hyperglycemia to worse outcome in critically ill children. Investigations in small, homogenous groups, such as trauma, sepsis, burn and neonatal patients, have shown negative associations between hyperglycemia and injury-specific outcomes and have elucidated previously proposed mechanisms of tissue injury in children. In addition, certain properties of hyperglycemia, such as duration, peak, and excursion, may be more relevant than absolute levels of glucose. Larger studies generalize findings to heterogeneous pediatric intensive care populations, across ages and diagnoses. Further, in studies accounting for insulin administration, no obvious increases in hypoglycemia-related morbidity have been noted. SUMMARY: Glucose control in pediatric intensive care has been receiving increasing attention. Large, prospective studies are needed to address certain issues in pediatrics, such as differences in diseases, target values, complications of disease, risks and sequelae of hypoglycemia and logistical challenges. PMID- 17285007 TI - Stress-induced insulin resistance: recent developments. AB - PURPOSE OF REVIEW: Interest in stress-induced insulin resistance has increased during the past 5 years. Relevant clinical and mechanistic investigations during the past year will be reviewed. RECENT FINDINGS: Recent trials of intensive insulin therapy in intensive care units have brought attention to a high incidence of hypoglycemic episodes with such treatment. The clinical relevance of such hypoglycemia has been shown to be minor, however. Furthermore, animal and in vitro work further supports the finding that glucose control, rather than glycemia-independent effects of insulin, is the primary mechanism of action of intensive insulin therapy. In elective surgery, cohort studies show an association between intraoperative hyperglycemia and postoperative morbidity. Beneficial effects of preoperative oral carbohydrate treatment on immunocompetence and cardiac contractility have been demonstrated. Laparoscopic segmental colectomy was associated with considerably attenuated derangements in glucose metabolism compared with conventional, open surgery. SUMMARY: Better methods of insulin dosing and administration and glucose monitoring are warranted to further minimize the risks of intensive insulin therapy. In elective surgery, perioperative measures such as preoperative oral carbohydrate treatment and laparoscopic techniques attenuate metabolic and other physiological derangements and such methods should be integrated into perioperative care protocols to minimize morbidity and enhance recovery. PMID- 17285009 TI - Hypoglycemia in the intensive care unit. AB - PURPOSE OF REVIEW: To review recent articles and evaluate hypoglycemia as a major complication of intensive insulin therapy in anticipation of emerging data from current clinical studies. RECENT FINDINGS: Following the 2001 landmark Leuven study demonstrating that intensive insulin therapy in the surgical intensive care unit reduces mortality, many studies have evaluated aspects of intensive insulin therapy with respect to improved clinical outcome and the impact of hypoglycemia. Specific risk factors for hypoglycemia in the intensive care unit with intensive insulin therapy are diabetes, octreotide therapy, nutrition support, continuous venovenous hemofiltration with bicarbonate replacement fluid, sepsis and need for inotropic support. In prospective studies with a comparator group, the incidence of hypoglycemia in intensive care unit patients treated with intensive insulin therapy is up to 25%, corresponding to a relative risk of 5.0. In studies without a comparator group, however, the incidence is less than 7%. SUMMARY: Hypoglycemia is associated with adverse outcome in intensive care unit patients. It remains unclear whether intensive insulin therapy-induced hypoglycemia per se is responsible for this adverse outcome. The threat of hypoglycemia is a barrier to intensive insulin therapy in critical care, supporting the need for frequent glucose monitoring, readily available concentrated intravenous dextrose infusions, better training of nurses and technological advances in glucose sensing and insulin-dosing algorithms. PMID- 17285010 TI - Practical aspects of intensive insulinization in the intensive care unit. AB - PURPOSE OF REVIEW: Strategies used for intensive insulin therapy of critically ill patients and differences of approach according to medical condition are reviewed. RECENT FINDINGS: Acceptance of proposed glycemic targets for critically ill patients has been tempered by uncertainties about benefit of strict glycemic control for specific target subpopulations, differences between treatment centers, optimal timing and duration of intervention, and safety. Present-day intravenous insulin infusion protocols may perform well only for restricted populations. Assessment of protocol performance requires knowledge of algorithm behavior on or near the narrow target range and, using the patient as unit of observation, examination of glycemic variability. Systems of the future will permit adjustment of algorithm parameters to meet individual- or population specific targets and match carbohydrate exposure. SUMMARY: Attainment and preservation of glycemic control among critically ill patients are best attempted with intravenous insulin infusion. Advances in the design of decision support and insulin delivery systems, and progress in the technology of continuous blood glucose monitoring, are likely to reduce the risk of hypoglycemia, without compromise of target range control, such that the patient outcomes enjoyed by experienced centers in the future will prove generalizable to others through the extension of new technologies. PMID- 17285012 TI - Effect of nutritional support on glucose control. AB - PURPOSE OF REVIEW: There is evidence that maintaining a normal glycemia level in critically ill patients has beneficial effects on outcome. Strategies aimed at lowering glycemia are based on the understanding of mechanisms regulating glucose metabolism. RECENT FINDINGS: Activation of AMP protein kinase in skeletal muscle and in the liver leads to a reduction in glucose production, a stimulation of glucose uptake, and a lowering of glycemia. These mechanisms appear to be activated during exercise, or by the endogenous adipokine adiponectin. Alterations in adiponectin concentrations during critical illness may thus play a role in the metabolic stress responses. In addition, AMP-activated protein kinase is the target for drugs (metformin, thazolidinediones), which may be of interest in the intensive care unit. Besides insulin, plasma glucose concentrations may be lowered by hypocaloric feeding, or by feeding 'diabetic' formula with low glucose content and supplemented with fructose. Whether such approaches lead to beneficial effects comparable to those observed with insulin remains to be established. SUMMARY: Recent findings regarding the molecular mechanisms underlying glucose transport and metabolism are summarized, and potential strategies other than insulin are outlined which may contribute to lowering glycemia in critically ill patients. PMID- 17285013 TI - Current world literature. Lipid metabolism and therapy. PMID- 17285011 TI - Current controversies around tight glucose control in critically ill patients. AB - PURPOSE OF REVIEW: This review updates our knowledge on the benefits and risks of tight glucose control by intensive insulin therapy in critically ill patients, as well as discussing unanswered questions related to the subject. RECENT FINDINGS: At the cellular level, the toxic effects of elevated and highly variable glucose concentration are related to an increase in oxidative stress and to several toxic intracellular derivates generated as by-products of the glycolytic pathway. Clinically, several recent studies have suggested that the optimal target for blood glucose may be higher than the 'normal' values of 4.4-6.1 mmol/l for various categories of patients. Also, the variability in glucose level appears to be an important determinant of glucose toxicity. Conflicting data on the hazards of hypoglycaemia are emerging. SUMMARY: Practical recommendations for the implementation of tight glucose control using intensive insulin therapy cannot be disseminated until questions relating to optimal blood glucose level and the corresponding categories of patients have been resolved. The issues of glucose variability and the most efficient method of preventing hypoglycaemia will probably represent important parameters for comparing the safety and quality of protocols used for tight glucose control. PMID- 17285014 TI - Bibliography. Current world literature. Minimally invasive surgery in urology. PMID- 17285015 TI - Laparoscopic radical nephroureterectomy for transitional cell carcinoma: where are we in 2007? AB - PURPOSE OF REVIEW: Nephroureterectomy has undergone critical changes during the past 15 years with the advent of the laparoscopic approach. New data supporting laparoscopic nephroureterectomy (LNU) continue to emerge as new techniques are developed and current approaches refined. The purpose of this study was to investigate the findings within LNU from the past 2 years as an evolving although proven modality for treatment of upper-tract transitional cell carcinoma (TCC). RECENT FINDINGS: Intermediate outcomes continue to be published equating the oncologic efficacy and perioperative parameters (i.e. blood loss and pain medication requirements) of LNU to those of open nephroureterectomy, allaying previous arguments against the minimally invasive approach. Newer approaches to the nephrectomy segment of LNU have been described, including robot assistance in retroperitoneoscopic cases and hand-assisted laparoscopic nephrectomy without the use of a hand-port. Data supporting specific approaches to the distal ureter have been published, including implementing robotics and flexible cystoscopy. SUMMARY: Findings over the past 2 years show both the continued progress of LNU and the need for further evolution to optimize patient morbidity and oncologic outcomes. As laparoscopic training is integrated into urologic residency programs, standardizing the variables within LNU will be paramount. PMID- 17285016 TI - Expanding the indications for laparoscopic radical nephrectomy. AB - PURPOSE OF REVIEW: Laparoscopic radical nephrectomy is an established treatment for patients with clinical T1 renal cell carcinoma who are unsuitable for nephron sparing surgery. In this review we summarize the expanding indications for laparoscopic nephrectomy, including large tumors, locally advanced disease, venous thrombi and cytoreductive surgery. RECENT FINDINGS: Laparoscopic nephrectomy remains the foremost conventional laparoscopic procedure in urologic surgery. Multiple studies have demonstrated the feasibility of laparoscopic radical nephrectomy for stage T2 tumors, showing less morbidity and earlier return to activity compared to the open approach. Confirmation of durable oncologic control requires randomized prospective trials with longer follow-up. With growing experience, laparoscopic surgery has been extended to patients with renal cell carcinoma associated with limited local invasion and lymph node metastases. Experimental studies demonstrate the technical feasibility of laparoscopic radical nephrectomy in the presence of renal vein and inferior vena cava thrombi. In well-selected patients with metastatic renal cell carcinoma, laparoscopic cytoreductive nephrectomy can be performed safely, with less morbidity than open nephrectomy. SUMMARY: Minimally invasive surgery results in significantly less postoperative morbidity than does open surgery. The intermediate oncologic outcomes of laparoscopic radical nephrectomy for advanced renal cell carcinoma are comparable to those historically achieved with open radical nephrectomy. Longer follow-up is needed to confirm survival equivalence. PMID- 17285017 TI - Laparoscopic radical cystectomy with urinary diversion: what is the optimal technique? AB - PURPOSE OF REVIEW: Laparoscopic prostatectomy has become a standardized procedure; consequently, many urologic surgeons have mastered it. Using the knowledge gained from this procedure, some laparoscopic urologic surgeons have also been successfully performing laparoscopic radical cystectomy. We review the current literature to determine the optimal technique for laparoscopic radical cystectomy. RECENT FINDINGS: Three techniques for the extirpative aspect of laparoscopic radical cystectomy have been described: robot-assisted, hand assisted and pure laparoscopic surgery. Creation of the urinary bladder has been performed via both intracorporeal and extracorporeal techniques with more recent studies favoring the extracorporeal creation of the urinary diversion. SUMMARY: Laparoscopic radical cystectomy has become a standard procedure at many laparoscopic centers worldwide. The procedure is feasible with reproducible results. It appears to offer the patient all the advantages of other minimally invasive surgeries with respect to postoperative recovery. PMID- 17285018 TI - Laparoscopic radical prostatectomy: current techniques. AB - PURPOSE OF REVIEW: Laparoscopic radical prostatectomy is now considered the standard of care at many centers for the treatment of localized prostate cancer. As with other surgical approaches, there has been an evolution in surgical techniques. Critical evaluation of the effects of these changes on clinical and pathologic outcomes continues. RECENT FINDINGS: The technique of nerve sparing laparoscopic radical prostatectomy should attempt to mimic the techniques and outcomes of open surgery, while maintaining the advantages of reduced blood loss and morbidity, and greater visualization. Long-term functional and oncologic outcomes appear equivalent to open surgery. Surgical approaches based upon recent anatomic studies of the periprostatic neuroanatomy continue to spur both advances and debate. Athermal dissection near the neurovascular bundle, along with high release of the surrounding fascia, may hasten recovery of erectile function. Techniques of sparing or reconstructing the puboprostatic ligaments and support of the bladder are evolving in efforts to improve continence results. Debate over the merits of transperitoneal vs. extraperitoneal approaches to laparoscopic prostatectomy continues. SUMMARY: Nerve sparing laparoscopic radical prostatectomy, although technically challenging, has proven to be an excellent alternative for dedicated centers wishing to provide a minimally invasive surgical option to their patients with localized prostate cancer. PMID- 17285019 TI - Current opinion in urology: new insights into nephrolithiasis. AB - PURPOSE OF REVIEW: Recent studies in nephrolithiasis have investigated why stones form, improvements in medical therapy, and advances in surgical therapy. We outline recent research in these areas. RECENT FINDINGS: We describe a series of articles characterizing the histopathology of Randall's plaques and the renal papillae in patients with nephrolithiasis, detailing genetic discoveries related to uric acid stones, describing further uses of alpha-antagonists in nephrolithiasis, and reporting improvements in extracorporeal shockwave lithotripsy technique and outcomes. SUMMARY: Characterization of the renal papillae and Randall's plaques in different types of stones may guide the urologist in treating stones and may lead to further research into how and where stones of different compositions form. PMID- 17285020 TI - Limitations of extracorporeal shock wave lithotripsy. AB - PURPOSE OF REVIEW: Extracorporeal shock wave lithotripsy (ESWL) is the preferred modality for the treatment of renal and upper ureteric calculi. The present review focuses on the limitations of ESWL, where recent developments have tried to identify patients who are unlikely to succeed with ESWL and where improvements in shock wave delivery may increase successful stone fragmentation. RECENT FINDINGS: Evaluation of patients prior to ESWL is especially important, and the use of imaging in the decision process, with the use of computed tomography attenuation values and skin-to-stone distance, can help improve our ability to identify suitable patients for shock wave treatment. Continued research into the methods of shock wave delivery techniques and lithotripter designs will help achieve better stone fragmentation rates with reduced side effects. SUMMARY: The importance of traditional factors in predicting ESWL success, such as stone size, location, composition and renal anatomy, are well known. More recently, authors have created nomograms to predict stone-free outcome after ESWL. Others have used the information obtained from computed tomography to predict stone comminution. In addition, modifications in shock wave delivery by altering shock rate and voltage have been researched in an effort to improve shock wave efficacy. PMID- 17285021 TI - Impact of flexible ureterorenoscopy in current management of nephrolithiasis. AB - PURPOSE OF REVIEW: Flexible ureterorenoscopy continues to assume an increasing role in the armamentarium of the endourologist. Here, we summarize some of the important papers over the past 12-18 months that continue to define its place in the treatment of upper tract calculi. RECENT FINDINGS: We concentrate on the indications for flexible ureterorenoscopy for upper tract calculi, and discuss the techniques and strategies that can be employed in different situations, including its use in combination with extracorporeal shockwave lithotripsy and percutaneous nephrolithotomy. The developing technology behind flexible ureterorenoscopy is also discussed. SUMMARY: Flexible ureterorenoscopy is emerging as one of the mainstays of treatment of upper tract calculi, rather than as a technique for the exclusive use of the enthusiast. Technical advances in image quality and in making the scopes more durable are likely to lead to an increasing use of this technique in more urology departments in the future. PMID- 17285022 TI - Minimizing and managing bleeding after percutaneous nephrolithotomy. AB - PURPOSE OF REVIEW: As urologists will continue to rely on percutaneous nephrolithotomy, a clear understanding of its associated bleeding risks and management is mandatory. RECENT FINDINGS: Despite advances in lithotripsy technology, bleeding continues to be a cause of patient morbidity in percutaneous nephrolithotomy. Although most patients can be managed conservatively, a subset of patients will require endovascular embolization for vascular control. Investigators have identified risk factors and described management options. The use of different dilators and tract size continues to be examined. Additionally, novel applications of proclotting agents as well as direct renal and tract electrocauterization immediately postpercutaneous nephrolithotomy have been reported to decrease transfusions. Finally, initial access obtained by the urologist is associated with less bleeding and higher stone-free rates. SUMMARY: Optimal renal access is the most critical factor influencing surgical success and minimizing overall blood loss. Although real-time ultrasonography may add to the safety of the initial access, surgeon experience is the key factor. As such, the urologist must be actively involved in tract placement. Clinically significant bleeding can be treated conservatively in a majority of cases with tamponade nephrostomy tubes with or without transfusions. Arterial hemorrhage, pseudoaneurysms, and arterial-venous fistulas, however, require prompt intervention with angiographic embolization. PMID- 17285023 TI - Management of urolithiasis in the congenitally abnormal kidney (horseshoe and ectopic). AB - PURPOSE OF REVIEW: Urolithiasis in horseshoe and ectopic kidneys presents unique challenges in the decision-making and technical aspects of stone treatment. Specific renal anatomy, stone size and associated conditions such as ureteropelvic junction obstruction are factors that may influence treatment. Detailed review of imaging is important to ensure efficient stone treatment and minimize complications. RECENT FINDINGS: Widespread use of extracorporeal shockwave lithotripsy for calculi in congenitally abnormal kidneys is now giving way to stone-size and anatomy-appropriate therapeutic decision making. Multiple modalities including shockwave lithotripsy, ureteroscopy, percutaneous nephrolithotomy and laparoscopy are being employed in this group of patients. SUMMARY: Treatment decisions for stones in horseshoe and ectopic kidneys can be challenging, and must be made on an individual basis taking into account multiple variables. PMID- 17285024 TI - Management of urolithiasis with chronic renal failure. AB - PURPOSE OF REVIEW: Epidemiological trends of urolithiasis and the prevalence of renal failure in patients with stones have changed. This is the era of minimally invasive therapy for stone disease. We review the impact of minimally invasive therapy on the management of urolithiasis in patients with renal failure and its outcome. RECENT FINDINGS: The prevalence of urolithiasis has reached its peak and plateaued in Europe and North America while it is still rising in the underdeveloped countries. The prevalence of renal failure in patients with chronic renal failure has reduced by half over the last decade. Minimally invasive therapy like percutaneous nephrolithotripsy has fared better than open stone surgery in all respects. Patients with kidney stones do not have normal renal function. Recently, cystine stones, and stones in patients with renal tubular acidosis and bowel disease were shown to affect renal function significantly. SUMMARY: Management of stones in chronic renal failure is challenging. Efforts should be made to minimize renal injury. Once a 'stone-free' kidney is achieved, steps should be taken to conserve renal function and address the issue of recurrence. PMID- 17285025 TI - Management of stones in calyceal diverticulum. AB - PURPOSE OF REVIEW: Congenital abnormities in urology are very common. These abnormalities include calyceal diverticula, which are frequently diagnosed as an incidental finding. Once symptomatic, calyceal diverticula have to be located by accurate imaging and then treated in an appropriate manner. RECENT FINDINGS: Possible methods of treatment in calyceal diverticula are generally the same as in other abnormalities of the kidney: extracorporeal shock-wave lithotripsy, endoscopic procedures, percutaneous procedures, laparoscopy and open surgery. It is important to find the exact location of the stone-bearing diverticulum and various imaging techniques may be used for this purpose. Metabolic work-up remains important. SUMMARY: There is a strong trend towards endoscopical and laparoscopical treatment in renal abnormalities such as calyceal diverticula. A combination of these two methods seems to be appropriate in some cases. PMID- 17285027 TI - Bibliography. Current world literature. Urolithiasis. PMID- 17285026 TI - Management of stones in neurological patients. AB - PURPOSE OF REVIEW: Patients with neurological disorders and urinary stone disease pose a significant challenge to the urologist, and possibly as a consequence, the literature is sparse about this small but important group of patients who are at an increased risk of urolithiasis, complications following surgical intervention and stone recurrence. Thus, this review has included publications from the last 5 years. RECENT FINDINGS: In the last few years several studies have reported the challenge for getting these patients stone-free and highlighted the risk management issues that need to be covered when considering surgical intervention. Similarly, these patients are at increased risk of stone recurrence and the published literature illustrates the need for consistent posttreatment regimens to minimize further stone formation--an area which presents great opportunities for research. All the publications emphasize the need for these patients to be assessed in dedicated stone centres with access to all the various modalities for treatment. SUMMARY: Patients with spinal neuropathy and urolithiasis pose a significant operative challenge, and there needs to be an established set of evidence-based guidelines to assist medical decision making for this high-risk population group. Unfortunately, the evidence to date is weak and more work is necessary to provide the basis for improving patient care. PMID- 17285032 TI - Patient safety: honoring advanced directives. AB - Healthcare providers typically think of patient safety in the context of preventing iatrogenic injury. Prevention of falls and medication or treatment errors is the typical focus of adverse event analyses. If healthcare providers are committed to honoring the wishes of patients, then perhaps failures to honor advanced directives should be viewed as reportable medical errors. PMID- 17285033 TI - Cultural considerations and the Hispanic cardiac client. AB - This article examines the cultural influences of the Hispanic patient, such as health beliefs, communication styles, family and religious values, and time perception. In order to design and deliver individualized comprehensive care with the client and family, these assessment factors must be explored to create a plan of care that is tailored to meet the individualized needs of the patient and family. Understanding cultural influences that are important to the Hispanic cardiac client in the home care setting will have a positive impact on the nurse patient relationship, the plan of care, and the management of the cardiac disease. PMID- 17285035 TI - Research on changing practitioner and patient behavior. AB - The Institute of Medicine's report "Crossing the Quality Chasm" (2001) indicates that it takes 17 years, on average, for knowledge generated by randomized trials to be adopted in practice if there is no effective intervention in place to promote the evidence. Influencing provider behavior is a formidable task, and many strategies traditionally used, such as unsolicited distribution of consensus recommendations or guidelines, and traditional didactic lectures and seminars, have generally been proven to be ineffective in changing clinical practices. The summaries that follow provide an overview of recently published, research-based works on strategies to change clinician and/or patient behavior. Two articles focus on improving hypertension management and two focus on improving heart failure management, conditions that are seen at very high levels in home care. We hope that the following summaries will stimulate some thinking about strategies that can be tried in home care organizations to promote the adoption of evidence based care. For additional details about the intervention and research findings, we suggest that our readers refer to the original articles. PMID- 17285036 TI - Venous thromboembolism: a common and preventable condition. Implications for the home care nurse. PMID- 17285038 TI - The effect of frontloading visits on patient outcomes. AB - Frontloading, providing 60% of planned visits in the first 2 weeks of the home healthcare episode, was tested in two groups of patients: insulin-dependent patients with diabetes and patients with a primary diagnosis of heart failure. Frontloading was effective for patients with heart failure, decreasing rehospitalization by more than half (39.4-16%), with fewer visits (15.5 vs. 9.5) and equal clinical outcomes and patient satisfaction. There were no significant differences in outcomes for patients with diabetes. PMID- 17285039 TI - Nursing and therapy: partnering for successful niche programs. AB - Changing market environment, increased patient expectations, and emphasis on improving functional outcomes led to the development of orthopedic and cardiac niche programs at one agency. Through these programs, it was learned how to best utilize the strengths of nursing and therapy to achieve maximum success for both patients and the organization. PMID- 17285040 TI - In-home wound care management utilizing information technology. AB - Chronic wounds are a major healthcare crisis, presenting challenges for home health agencies lacking specially trained staff to properly monitor and manage these wounds. Consequently, the home health industry needs to improve wound management methods and technologies to properly care for patients with chronic wounds. Saint Francis University's Center of Excellence for Remote and Medically Under-Served Areas partnered with a home health agency (University of Pittsburgh Medical Center Lee Regional Community Nursing Service) to identify a solution to this problem. PMID- 17285041 TI - Home care for the high-risk neonate: success or failure depends on home health nurse funding and availability. PMID- 17285042 TI - Blood cholesterol levels: more than just "good, bad, and ugly" (abnormal levels). PMID- 17285043 TI - Promises our home care clients cherish. PMID- 17285044 TI - Segmental malalignment with the Bryan Cervical Disc prosthesis--does it occur? AB - The early clinical results with the Bryan Cervical Disc prosthesis are encouraging but 2 recent small published series have noted postoperative radiologic kyphosis of the functional spinal unit (FSU) of 4 and 6 degrees. The current study was undertaken to accurately assess the extent of any sagittal deformity after the use of this prosthesis in a substantial, multisurgeon case series. The neutral, erect x-rays of 67 consecutive patients (88 disc levels) operated by one of 3 surgeons, were examined using manual and digital image analysis techniques for FSU sagittal angulation (lordosis), prosthesis shell angulation, segmental olisthesis, and overall cervical alignment. Measurement accuracy was confirmed using interobserver and intraobserver studies. There was a median loss of 2 degrees in FSU lordosis when compared with preoperative imaging (P<0.0001, range: 8-degree loss to 5-degree gain). A median 2 degrees of prosthesis shell kyphosis also occurred (range: 15-degree kyphosis to 12-degree lordosis) but shell angulation correlated weakly with the change in FSU lordosis (rs=0.37, P=0.001). There was a significant difference in the median loss of FSU lordosis between surgeon 1 and surgeons 2 and 3 (3.5 degrees vs. 2 degrees, P=0.005). Median olisthesis of the prosthesis shells was -0.1 mm (range: +1.5 to 2.5 mm). Median postoperative overall cervical lordosis reduced by 4 degrees (P<0.004). A small loss in median FSU lordosis was observed after insertion of the Bryan disc. The observed changes were generally small but varied among both the patients and the surgeons, suggesting that variables may exist which contribute to postoperative sagittal alignment. These are the subject of an accompanying study. PMID- 17285045 TI - An analysis of factors causing poor surgical outcome in patients with cervical myelopathy due to ossification of the posterior longitudinal ligament: anterior decompression with spinal fusion versus laminoplasty. AB - OBJECTIVE: We compared the surgical outcome of anterior decompression with spinal fusion (ASF) with the surgical outcome of laminoplasty for patients with cervical myelopathy due to ossification of the posterior longitudinal ligament. METHODS: The study group comprised 19 ASF patients (A-group) and 40 laminoplasty patients (P-group) treated from 1993 to 2002 with 1 year or longer follow-up. The Japanese Orthopedic Association scoring system was used to evaluate cervical myelopathy, and the recovery rate calculated 1 year after surgery. RESULTS: The mean recovery rate was 68.4% in the A-group and 52.5% in the P-group (P<0.05). Fifteen patients had a recovery rate less than 40%: 2 in the A-group and 13 in the P-group. One P group patient and none of the A-group patients developed postoperative aggravation of their neurologic status. The P-group was divided into 2 subgroups: a good outcome group comprising patients whose recovery rate was 40% or higher (n=27) and a poor outcome group comprising patients whose recovery rate was less than 40% (n=13). The mean age at surgery was 59.9 years in the good outcome group and 68.0 years in the poor outcome group (P<0.05). The mean range of intervertebral mobility at maximum cord compression level before surgery was 6.9 degrees in the good outcome group and 10 degrees in the poor outcome group (P<0.05). CONCLUSIONS: These results demonstrated that the surgical outcome of ASF was superior to the surgical outcome of laminoplasty. Elderly patients treated with laminoplasty showed an especially poor surgical outcome. We suggest that hypermobility of vertebrae at the cord compression level is a risk factor for poor surgical outcome after laminoplasty. Based on these results, we recommend that ASF should be the first choice of treatment for patients with significant ossification of the posterior longitudinal ligament and a hypermobile cervical spine. When laminoplasty is used for such cases, the addition of posterior instrumented fusion would be desirable for stabilizing the spine and decreasing damage to the spinal cord. PMID- 17285046 TI - Kyphosis one level above the cervical disc disease: is the kyphosis cause or effect? AB - If present, kyphotic angulation is generally at the level of the cervical disc disease (CDD) in the neck, but sometimes occurs at one level above the CDD. We name this situation as kyphosis one level above (KOLA). KOLA CDD has not been studied previously. In this study, we present 18 patients who had KOLA among 147 patients operated for CDD over a 5-year period. Seven of these 18 patients also received surgery for their KOLA. As new, surgical treatment of kyphotic level was performed with plating and without bony fusion in 5 patients. Clinical outcomes (according to Odom's criteria) and kyphotic corrections of KOLA patients receiving and not receiving surgery for their kyphosis during were compared. The 7 KOLA patients having surgery to correct the kyphosis had a mean 20.14+/-3.13 degrees correction in their kyphosis (from mean 12.85 to -7.28 degrees), whereas the 11 patients undergoing surgery only for CDD showed only a mean 3.00+/-2.52 degrees correction (from mean 7.45 to 4.45 degrees). When kyphotic corrections were compared, statistically significant difference was found between 2 groups (P<0.01). Clinical outcome scores showed a trend towards improvement in the patients operated upon for kyphosis correction. KOLA may be a factor in the development of cervical disc herniation and spondylosis, and should be treated if more than 11 degrees. In cervical region, upper adjacent level disease may be an extension of KOLA. Larger studies can further define the relationship between KOLA and CDD, and indications for surgical correction of KOLA. PMID- 17285047 TI - Minimally invasive 2-level posterior cervical foraminotomy: preliminary clinical results. AB - INTRODUCTION: The management of cervical radiculopathy has undergone significant evolution, and the most recent advancement is the integration of minimally invasive surgical techniques. There have been relatively few reports in the medical literature describing the clinical results of minimally invasive cervical spine surgery. The authors describe the surgical indications, technique, and preliminary clinical outcomes in a series of patients who underwent the 2-level minimally invasive posterior cervical foraminotomy procedure. METHODS: This report is composed of 21 consecutive patients with cervical radiculopathy who underwent a minimally invasive 2-level posterior cervical foraminotomy at our institution between 2003 and 2005. Magnetic resonance imaging demonstrated foraminal or posterolateral pathology at 2 ipsilateral adjacent spinal levels in each patient. Radicular arm pain was the most common presenting symptom, and was encountered in all 21 patients. RESULTS: The mean follow up for the patients was 23 months (range 12 to 36). Complete resolution of preoperative symptoms was achieved in 19 out of 21 patients (90%). Sixteen patients were discharged home the same day of surgery, and the mean estimated blood loss was 35 mL (range 10 to 100 mL). There were no perioperative complications. CONCLUSIONS: Minimally invasive 2-level posterior cervical foraminotomy can be safely performed on an outpatient basis with results comparable to that of conventional foraminotomy. This procedure should be considered as a potential alternative to 2-level anterior cervical discectomy and fusion or open foraminotomy in selected patients. PMID- 17285048 TI - Clinical accuracy of cervicothoracic pedicle screw placement: a comparison of the "open" lamino-foraminotomy and computer-assisted techniques. AB - OBJECTIVE: Posterior transpedicular fixation at the cervicothoracic junction (CTJ) is increasing in popularity. However, the clinical accuracy of pedicle screw placement at the CTJ has not been specifically assessed. METHODS: Between January 2000 and July 2004, 60 consecutive patients underwent a variety of posterior spinal procedures necessitating pedicle screw placement at C7, T1, and T2. Thirty-two patients had cervicothoracic screws (3.5 to 4.5 mm) placed by an "open" technique (laminectomies or lamino-foraminotomies) and 28 patients with either a closed (before any decompression) 2-dimensional (n=19, fluoroscopy) or 3 dimensional (n=9, CT) computer-assisted technique. Screws were independently assessed for pedicle breach on postoperative CT and scored using a points-based classification system. RESULTS: The total number of screws placed was 86, 63 and 45 in the open, closed-2-dimensional and closed-3-dimensional groups, respectively. Overall, 61(70.9%), 51(81%), and 40(89%) screws were completely within the pedicle. In the open group, the majority of pedicle breaches were more than 2 mm [n=3 (<2 mm), n=20 (2-4 mm), n=2 (>4 mm)]. Screw violation occurred laterally 11/25(44%), medially 3/25(12%), inferiorly 7/25(28%), and superiorly 4/25(16%). In the closed technique, all breaches were lateral. Seventeen screws (n=11-2-dimensional, n=5-3-dimensional) breached the pedicle by a margin of less than 2 mm and 1 screw (2-dimensional) by 2 to 4 mm. Pedicle screw accuracy was significantly improved with computer-assisted techniques. However, there was no significant difference between the 2-dimensional and 3-dimensional techniques. For all patients, there were no clinically significant screw misplacements, nor any need for screw revision. CONCLUSIONS: Computer-assisted surgery allows for more accurate placement of pedicle screws at the CTJ. Although a higher proportion of major pedicular breaches occurred in the "open lamina/lamino foraminotomy" group, no screws required revision in either group. PMID- 17285049 TI - Use of small suture anchors in cervical laminoplasty to maintain canal expansion: a technical note. AB - OBJECTIVE: Open door laminoplasty is a commonly performed procedure for the treatment of cervical spine pathology. One complication of this procedure is closure of the hinge and subsequent restenosis. A simple and effective method of using suture anchors to stabilize posterior elements has been previously described. The aim of this paper is to describe our experience using 2.0-mm suture anchors to maintain canal expansion. METHODS: Results of 42-consecutive patients who were treated with a modified cervical open-door laminoplasty were reviewed. The modification involves the use of original Hirabayashi technique, but augmenting the canal expansion with 2.0-mm suture anchors at C3, C5, and C7 levels. Additionally, nonabsorbable sutures are placed at C4 and C6 levels as described by Hirabayashi. The technical issues and short-term radiographic outcomes were evaluated. RESULTS: None of the 42 patients who had the door secured with 2.0-mm suture anchors had closure of the hinge. Additionally, the suture anchors maintained their position without loosening or "pull-outs" on postoperative follow-up radiographs. There were 3 short-term complications: 1 was a small dural-tear which was repaired intraoperatively without further sequelae, and the other 2 were both epidural hematomas that required emergent return to the operating room for evacuation. All 3 patients had an uneventful recovery without a new neurologic deficit. CONCLUSIONS: This paper reviews a simple and effective method for maintaining canal expansion in open-door laminoplasty. Because of its technical simplicity, 2.0-mm suture anchors may be a safer alternative than other devices currently popular for this purpose. PMID- 17285050 TI - A novel source of cancellous autograft for ACDF surgery: the manubrium. AB - There are a variety of techniques and biologic options when performing interbody fusion during an anterior cervical discectomy and fusion (ACDF). Autologous graft provides high rates of fusion; however, complications associated with donor site morbidity from the iliac crest have prompted some surgeons to use alternative graft material. Ten patients (8 men, 2 women) with cervical radiculopathy underwent single-level ACDF with plate fixation, titanium mesh cage, and cancellous autograft from the manubrium. Cancellous bone was obtained through a cortical window on the anterior aspect of the manubrium through a 2-cm transverse incision. A minimum 1-year clinical and radiographic follow-up for all patients evaluated fusion rates, donor site morbidity, and patient satisfaction. All patients had immediate postoperative resolution of radicular symptoms and radiographic evidence of solid fusion within 3 months. No patient complained of donor site pain and narcotic pain medication was not required after discharge. No complications associated with the manubrium donor site were noted; however, 1 female patient was dissatisfied with its cosmetic appearance. The manubrium is an effective, safe, and technically facile source of autologous bone graft that yields high fusion rates and patient satisfaction in contemporary ACDF surgery. This new technique to obtain cancellous graft from the manubrium combines the advantages of autologous bone without the morbidity of iliac crest harvest. PMID- 17285051 TI - Single level arthrodesis as treatment for midcervical fracture subluxation: a cohort study. AB - Although many different techniques exist for fusion of midcervical facet fracture dislocations, limiting arthrodesis to a single level could have a theoretical advantage: fewer fused segments could lessen long-term negative effects of fusion on adjacent segments. Therefore, we prospectively treated 22 consecutive patients with midcervical fracture dislocation without vertebral body fracture with single level arthrodesis even if anterior/posterior surgery were required. Twelve patients with unilateral facet subluxation underwent anterior cervical discectomy, distraction reduction with Caspar posts (AESCULAP, Tuttlingen, Germany) with allograft fusion and anterior cervical plating. Ten patients with any component of bilateral facet subluxation underwent anterior cervical discectomy, distraction reduction with Caspar posts, allograft fusion and plating followed by posterior lateral mass plating. No patients demonstrated worsening of nerve root or spinal cord function postoperatively. Interbody stability occurred in all cases. Only complications were 4 cases of pneumonia, 1 case of wound leakage, and 1 case of superficial wound infection. Good reduction was achieved for both unilateral and bilateral facet fractures. Single level interbody arthrodesis is safe and effective strategy with both unilateral and bilateral facet fractures. Single level arthrodesis may also offer long-term benefit compared with multilevel fusions. PMID- 17285052 TI - Caudal epidural injection for L4-5 versus L5-S1 disc prolapse: is there any difference in the outcome? AB - One hundred seventy-seven patients with radicular pain due to disc prolapse treated with caudal epidural injection were included in our study. All the injections were carried out between January 2000 and December 2004. Inclusion criteria include symptomatic disc prolapse diagnosed with magnetic resonance imaging scan, disc prolapse of 1 level only either L4-5 or L5-S1, leg pain for more than 4 wk and age more than 18. Exclusion criteria include multiple disc levels, spondylolithesis, spinal stenosis, cauda equina, and progressive neurologic deficits. Outcome Measures include Oswestry score and patient satisfaction and final outcome patient satisfaction either excellent (complete pain relief), good (minimal symptoms), moderate (some symptoms), no relief (symptoms unchanged), and worse (symptoms deteriorated). The final outcome is excellent (more than 6 mo pain relief), very good (3 to 6 mo pain relief), good (6 wk to 3 mo pain relief), fair (4 to 6 wk pain relief), brief (less than 4 wk pain relief), and no relief postal questionnaire sent and telephone interview done with the nonresponders. Ninety-six answered the postal questionnaire and this number increased to 136 after telephone interview. Forty-nine percent females and 51% males. Eighty-nine with L5-S1 disc prolapse and 47 with L4-5 disc prolapse. Caudal epidural not only relieve leg pain but also relieve back pain. There is no significant difference in the Oswestry disability index nor in the patient satisfaction nor the final outcome after caudal epidural injections for patients with disc prolapse L5-S1 and L4-5 ones. The number of patients who required surgery were much less than the literature figures 3.05%. There is no significant difference in the response after caudal epidural injection considering the sex only. The longest the back pain before injection is associated with the worst Oswestry disability index. PMID- 17285053 TI - PLIF with a titanium cage and excised facet joint bone for degenerative spondylolisthesis--in augmentation with a pedicle screw. AB - OBJECTIVES: To determine the validity of posterior lumbar interbody fusion (PLIF) using a titanium cage filled with excised facet joint bone and a pedicle screw for degenerative spondylolisthesis. METHODS: PLIF using a titanium cage filled with excised facet joint bone and a pedicle screw was performed in 28 consecutive patients (men 10, women 18). The mean age of the patients was 60 years (range, 52 to 75 y) at the time of surgery. The mean follow-up period was 2.3 years (range, 2.0 to 4.5 y). The operation was done at L3/4 in 5, L4/5 in 20, and L3/4/5 in 3 patients. The mean operative bleeding was 318+/-151 g (mean+/-standard deviation), and the mean operative time was 3.34+/-0.57 hours per fixed segment. Clinical outcome was assessed by Denis' Pain and Work scale. Radiologic assessment was done using Boxell's method. Fusion outcome was assessed using an established criteria. RESULTS: On Pain scale, 20 and 8 patients were rated P4 and P5 before surgery, and 11, 12, 2, 2, and 1 patients were rated P1, P2, P3, P4, and P5 at final follow-up, respectively. On Work scale (for only physical labors), 12 and 9 patients were rated W4 and W5, before surgery, and 12, 5, 1, and 3 patients were rated W1, W2, W3 and W5 at final follow-up, respectively. There was significant difference in clinical outcome (P<0.01, Wilcoxon singled rank test) The mean %Slip and Slip Angle was 17.9+/-8.1% and 3.9+/-5.8 degrees before surgery. The mean % Slip and Slip Angle was 5.4+/-4.4% and -2.0+/-4.8 degrees at final follow-up. There was a significant difference between the values (P<0.01, paired t test). "Union" and "probable union" was determined in 29 (93.5%) and 2 (6.5%) of 31 operated segments at 2.3 years (range, 2.0 to 4.5 y), postoperatively. CONCLUSIONS: PLIF using a titanium cage filled with excised facet joint bone and a pedicle screw provided a satisfactory clinical outcome and an excellent union rate without harvesting and grafting the autologous iliac bone. PMID- 17285054 TI - Is one cage enough in posterior lumbar interbody fusion: a comparison of unilateral single cage interbody fusion to bilateral cages. AB - Posterior lumbar interbody fusion (PLIF), as recommended with bilateral lumbar interbody cages and pedicle screw fixation, has increased the successful fusion rate to nearly 100%. Presently, a unilateral approach to the disc space with a variant of PLIF, the trans-foraminal interbody fusion is often used. There are few clinical studies of unilateral interbody fusion. The clinical and fusion results of unilateral interbody fusion are important as the usage of trans foraminal interbody fusion procedure increases. This retrospective study of 26 consecutive patients treated with a unilateral cage asks whether fusion healing and clinical outcome is comparable with that obtained with bilateral cages. In this study, there were no pseudarthroses, instrumentation failures, or significant subsidence at any of the single cage levels. Disc space height and foraminal height were restored by the surgery and maintained at last follow-up. Using Prolo scores, 23/26 patients had clinical success (88%), and 3 were unsuccessful. Fusion was successful at all single cage fusion levels and overall in 23/26 (88%) reviewing all levels of fusion. In conclusion, fusion and clinical success rates were not diminished by the use of a unilateral interbody cage rather than the recommended 2 cages. This retrospective comparative study is a Level III-2 Therapeutic Study investigating the results of unilateral PLIF with a single interbody cage compared with historical series with interbody cages. PMID- 17285055 TI - Thoracic pedicle screw insertion in scoliosis using posteroanterior C-arm rotation method. AB - OBJECTIVE: Previous researches have emphasized the importance and difficulties in accurate thoracic pedicle screw insertion in scoliosis patients. However, there has been no report on accuracy of the insertion using posteroanterior C-arm fluoroscopy rotated to allow en face visualization of the pedicle in humans. This study aimed to evaluate the accuracy of the thoracic pedicle screw insertion technique using a C-arm fluoroscopy rotation method for the treatment of scoliosis. METHODS: Between October 1997 and September 2005, 33 scoliosis patients who underwent surgical treatment with a total of 410 screws were analyzed. Eleven were male, 22 female and the mean age was 13.4 years. The mean preoperative Cobb angle was 59.7 degrees. Screws were inserted using the C-arm rotation method; screw positions were evaluated with postoperative computed tomography scans. RESULTS: The mean preoperative Cobb angle of 59.7 degrees was corrected to 18.9 degrees (range, 3 to 45 degrees) in the coronal plane (mean correction rate 68%). Postoperative computed tomography scans demonstrated 48 screws penetrated the medial (9 screws) or lateral (39 screws) pedicle cortex with a mean distance of 3.1 and 3.6 mm, respectively. No screws penetrated the inferior or superior cortex in the sagittal plane. CONCLUSIONS: Thoracic pedicle screw insertion in scoliosis patients using the posteroanterior C-arm rotation method allows en face visualization of both pedicles by rotating the C-arm to compensate for the rotational deformity, making it a practical, simple and safe method. PMID- 17285056 TI - Intermediate screws in short segment pedicular fixation for thoracic and lumbar fractures: a biomechanical study. AB - To determine the effect of adding pedicle screws at the level of a burst fracture (intermediate screws) on the stiffness of a short segment pedicle fixation, an in vitro biomechanical study was carried out. Six fresh-frozen pig lumbar spine specimens were used. The flexibility of the intact specimens was examined in flexion, extension, lateral bending, and torsion. An unstable burst fracture model was created by the dropped-mass technique. The unstable spine specimens were instrumented with pedicle screws. The flexibility was tested again with and without intermediate screws. The addition of intermediate screws provided a smaller range of motion in flexion-extension (P<0.001), torsion (P<0.001), and lateral bending (P=0.014). The slopes of the load displacement curves increased in flexion (P<0.001), extension (P=0.003), lateral bending (P=0.003), and torsion (P=0.006), signifying a decrease in flexibility. The addition of intermediate screws at the level of a burst fracture significantly increases the stiffness of a short segment pedicular fixation. PMID- 17285057 TI - The incidence of multiple level noncontiguous vertebral tuberculosis detected using whole spine MRI. AB - The commonest site of osseous tuberculosis is the spine. Most vertebral lesions are contiguous. Current research indicates the incidence of multiple level noncontiguous vertebral tuberculosis is 1.1% to 16%. The aim of this study was to identify the incidence of multiple level noncontiguous vertebral tuberculosis using whole spine magnetic resonance imaging (MRI). A retrospective review was undertaken of case notes and whole spine MRI studies of all acute spinal infection cases that presented to a regional Spinal Unit over 3 years. Patients were included if spinal infection was identified by whole spine MRI and confirmed as tuberculosis by a combination of histology and microbiology. The incidence of multiple level noncontiguous vertebral tuberculosis was 71.4%. This is higher than previously quoted when MRI is not undertaken. Tuberculosis may affect the spine at multiple noncontiguous sites more frequently than thought previously. A large proportion of the affected noncontiguous sites may also be asymptomatic. We currently perform whole spine MRI on all patients with suspected spinal infection to aid detection of multiple level noncontiguous tuberculosis. PMID- 17285058 TI - An innovative broken pedicle screw retrieval instrument. AB - OBJECTIVE: To introduce a new broken pedicle screw fragment retrieval instrument, and evaluate its clinical viability and effectiveness. METHODS: Following basic retrieval contrivance of broken pedicle screws described in literature, a new retrieval instrument was designed and developed; introducing its mechanism, technical components, and use. This innovative apparatus proved successful not only in saw bone and cadaver trials but in 10 clinical cases as well. RESULTS: This particular unique instrument successfully retrieves broken pedicle screw fragments through original passage backing out the screw with preservation of pedicle integrity while maintaining pedicle biomechanics. No complications were observed. CONCLUSIONS: With solid scientific theoretical planning and experimentation, the new retrieval instrument design proved clinical practicality and efficacy. PMID- 17285059 TI - Surgical treatment of Charcot spine. AB - The authors report 4 cases of Charcot spine treated surgically. In the surgical treatment, combined anterior and posterior with extensive debridement, autogenous bone grafting, and posterior instrumentation is the main therapeutic modality. Some cases with mild bone destruction could be treated by posterior interbody fusion. For the unstable, symptomatic Charcot spine, surgical treatment can provide excellent results. PMID- 17285061 TI - Bony flexion-distraction injury of the lower lumbar spine treated with instrumentation without fusion and early implant removal: a method of treatment to preserve lumbar motion: two-year follow-up of a teenage patient. AB - Most single level bony flexion-distraction injuries can be treated in a brace. Internal fixation is required, however, when a patient fails brace treatment. Instrumentation is routinely left in place for a year or more and in an unfused spine can lead to early degenerative changes of the facets and disks. Implant removal once healing has occurred can preserve motion segments in the lumbar spine and offer an advantage in a young patient over instrumentation and fusion. A case report is presented of a 17-year-old female treated successfully with internal fixation without fusion of a bony flexion-distraction injury of the lower lumbar spine with early implant removal and 2-year follow-up. PMID- 17285060 TI - Sagittal split fractures in multilevel cervical arthroplasty using a keeled prosthesis. AB - This is a case report of intraoperative sagittal split fractures in multilevel cervical disc replacement using a keeled prosthesis. The patient's clinical course is discussed and outcomes measured with the SF-36 questionnaire, oswestry disability index, and visual analog scale neck pain are compared with the other patients at our institution that have undergone multilevel disc replacement. The patient did well and has not had any complications related to the device used or fractures. The risks and techniques to avoid this complication when using a keeled prosthesis are discussed in detail. PMID- 17285062 TI - Disorders of tumoral calcification of the spine: illustrative case study and review of the literature. AB - Tumoral calcium pyrophosphate dihydrate crystal deposition disease and tumoral calcinosis (TC) are rare non-neoplastic conditions which may cause symptoms of spinal cord compression when they manifest in the perispinal tissues. There is little information available to compare these conditions with each other. We report a case of a patient with such a calcified mass impinging on the spinal cord. A 39-year-old woman on hemodialysis presents with progressive quadriparesis and monoplegia and is found to have a large calcified mass impinging on the spinal cord at the level of C3-4. The mass is excised by an anterior approach with corpectomy and fusion. Pathology was tumoral calcium pyrophosphate dihydrate crystal deposition disease versus TC. Both conditions are very rare in the perispinal tissues with 21 reported cases of tumoral calcium pyrophosphate dihydrate deposition disease and 39 cases of TC. Both cause compressive symptoms depending on the site of occurrence. Tumoral calcium pyrophosphate deposition disease is characterized by smaller, round, masses typically in ligamentous structures which may erode into adjacent bone. Tumoral calcinosis displays larger, lobulated, irregular lesions which do not erode into bone. Either lesion may contain calcium pyrophosphate dihydrate or hydroxyapatite. Treatment is surgical decompression, though lesions may recur. PMID- 17285063 TI - Intraoperative neuromonitoring detects thrombotic occlusion of the left common iliac arterial bifurcation after anterior lumbar interbody fusion: case report. AB - Prompt recognition of acute or delayed vascular insults during anterior spinal reconstructive surgery of the lower lumbar levels is paramount for successful intervention and prevention of sequelae. Although surgical exposure of the lower lumbar levels requires mindful dissection and cautious retraction of abdominal vessels, ischemic insult due to partial or complete occlusion of the iliac arteries may go undetected without adequate surgical monitoring. We present a case of progressive thrombotic occlusion of the left common iliac artery detected by intraoperative spinal cord monitoring using somatosenory evoked potentials (SSEPs) at the peripheral and central levels. Surgical monitoring using palpation of vessels and pulse oximetry of the great toe were initially proposed as simple and relatively inexpensive modalities for routine surgical monitoring. Subsequently, monitoring cortical SSEPs were combined with great toe pulse oximetry to advance continuous routine surgical monitoring. However, using only cortical SSEPs predisposes such protocols to an inherently higher risk of false positives. Neuromonitoring protocols should rely heavily on the replication of waveforms recorded at multiple sites along the neural pathway. PMID- 17285064 TI - Lateral mass screws: anatomy is the key, not image guidance! PMID- 17285079 TI - [Multiple trauma and critical instability in the same breath]. PMID- 17285080 TI - [Management of the unstable patient with multiple trauma]. AB - The management of the patient with multiple trauma in unstable condition must be adapted to the means available (or unavailable) on site, i.e., trained personnel, material means, and the possibility of evacuation to a trauma center. This may require a multi-stage surgical strategy based on clinical examination and available imaging resources. Patients with multiple trauma in unstable condition should be brought to the operating room promptly for life-saving or stabilizing interventions (Extreme Urgency). The patient may then undergo further stabilization of vascular volume, coagulation, and metabolic deficits while simultaneously undergoing a more detailed clinical and radiologic evaluation; he may then return to the operating room within six hours for more definitive repair of urgent lesions (First Urgency). Once the patient is stable enough for evacuation, he should be transferred to a trauma center for definitive surgical care. PMID- 17285082 TI - [Surgery treatment of rectal cancer]. AB - Surgical resection is the only curative procedure for carcinoma of the rectum. Heald's development of total mesorectal excision has made it the standard approach for mobile, non-fixed tumors; it permits optimal local control with less than 10% local recurrence at five years and minimizes nerve damage and genito urinary complications. Although initial short-term results of laparoscopic approaches are very promising, the final role of laparoscopy has not yet been established. Neo-adjuvant radiotherapy should be proposed for locally advanced (T3, T4, and/or N+) tumors of the low and mid-rectum. Radiochemotherapy coupled with intersphincteric dissection offers hope for sphicter-sparing extirpation of even the lowest of rectal cancers. Local resection through a trans-anal approach may be considered for small (<3 cm.), mobile, well-differentiated tumors lying within 8 cm. of the anal verge if rectal echo-endoscopy shows an in-situ tumor or a T1 lesion with no evidence of lymphadenopathy. Future strategies may enlarge the indications for local resection if and when radiochemotherapy can achieve a complete local response (tumor sterilization). PMID- 17285081 TI - [Duodenogastric and gastroesophageal bile reflux]. AB - This study reviews current data regarding duodenogastric and gastroesophageal bile reflux-pathophysiology, clinical presentation, methods of diagnosis (namely, 24-hour intraluminal bile monitoring) and therapeutic management. Duodenogastric reflux (DGR) consists of retrograde passage of alkaline duodenal contents into the stomach; it may occur due to antroduodenal motility disorder (primary DGR) or may arise following surgical alteration of gastoduodenal anatomy or because of biliary pathology (secondary DGR). Pathologic DGR may generate symptoms of epigastric pain, nausea, and bilious vomiting. In patients with concomitant gastroesophageal reflux, the backwash of duodenal content into the lower esophagus can cause mixed (alkaline and acid) reflux esophagitis, and lead, in turn, to esophageal mucosal damage such as Barrett's metaplasia and adenocarcinoma. The treatment of DGR is difficult, non-specific, and relatively ineffective in controlling symptoms. Proton pump inhibitors decrease the upstream effects of DGR on the esophagus by decreasing the volume of secretions; promotility agents diminish gastric exposure to duodenal secretions by improving gastric emptying. In patients with severe reflux resistant to medical therapy, a duodenal diversion operation such as the duodenal switch procedure may be indicated. PMID- 17285084 TI - [Organ harvesting. 2. The kidneys]. PMID- 17285083 TI - [Esophagectomy by triple approach: primary thoracotomy, laparotomy, and cervicotomy - The MacKeown Procedure]. PMID- 17285085 TI - [Calculous cholecystitis and common duct stones: combined intra-operative treatment]. PMID- 17285086 TI - [Littoral cell angioma of the spleen]. PMID- 17285087 TI - [Paraesophageal mass in the posterior mediastinum]. PMID- 17285088 TI - [Gangrene of the ligamentum teres hepatis]. PMID- 17285089 TI - [Bacterial meningitis from a gastrointestinal source]. PMID- 17285090 TI - [About: "Surgical management of post-operative peritonitis" to C. Mariette]. PMID- 17285091 TI - Continuous glucose monitoring. PMID- 17285092 TI - Angeliq for treatment of menopausal symptoms. PMID- 17285094 TI - Treatment characteristics and illness burden among European Americans, African Americans, and Latinos in the first 2,000 patients of the systematic treatment enhancement program for bipolar disorder. AB - OBJECTIVE: Across ethnicity/race, prevalence rates of bipolar disorder are similar. However, African Americans and Latinos may receive less specialty mental health treatment and different medications, and may be less adherent to treatment regimens than European American patients. This study compared illness characteristics, treatment history, and overall functioning in a sample of European American, African American, and Latino patients with bipolar disorder. METHODS: The samples were drawn from the first 2,000 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder. There were 1,686 European Americans, 65 African Americans, and 77 Latinos. The data were collected upon study entry, with structured interviews, clinicianrated forms, and self report. RESULTS: African Americans had a greater likelihood of psychosis and fewer psychiatric medication prescriptions than did European Americans. Latinos had greater alcohol comorbidity, fewer psychiatric medication prescriptions and specialty treatment visits, and more frequent religious service attendance than did European Americans. Depression and manic episode severity and functional outcomes were similar across groups. CONCLUSIONS: Patients with bipolar disorder who are members of ethnic/racial minority groups continue to receive less intensive specialized mental health treatment than do European American patients. These findings may be related to provider, patient, or provider-patient relationship variables. Despite treatment differences and greater comorbidity and sympomatology, there were no differences among the three groups in overall functioning, suggesting additional outcome measurement is warranted. PMID- 17285095 TI - Effect of mirtazapine orally disintegrating tablets on health-related quality of life in elderly depressed patients with comorbid medical disorders: a pilot study. AB - BACKGROUND: There is a need for additional studies on the quality of life (QOL) of elderly depressed subjects with medical comorbidity. METHOD: We conducted a 10 week, open trial of mirtazapine orally disintegrating tablets in 16 elderly subjects with major depressive disorder and one or more serious medical illnesses. Quality of life was measured by the Medical Outcomes Study Short Form 36 Health Status Survey (SF- 36). RESULTS: Treatment with mirtazapine was associated with significant reductions in clinical global impressions-severity of illness scale (CGI-S) score, the Hamilton rating scale for anxiety (HAM-A) total score, the 17-item Hamilton rating scale for depression (HAM-D) total score and the Beck depression inventory (BDI) total scores. The SF-36 "physical functioning", "role limitation physical", "vitality", "social functioning", "role limitation emotional", and "mental health" domains improved significantly. The mean mirtazapine dose at endpoint was 35 mg per day. The drug was relatively well tolerated except for three subjects who dropped out because of side effects. No drug-drug interactions or significant changes in blood pressure or heart rate occurred. CONCLUSION: Mirtazapine orally disintegrating tablets may improve depression, insomnia, anxiety, somatic symptoms, and certain quality-of-life measures in elderly depressed subjects with medical disorders. A randomized, placebo-controlled study is warranted to confirm these promising findings. PMID- 17285093 TI - Positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder. AB - OBJECTIVE: Memory for odors is often associated with highly emotional experiences, and odors have long been noted by clinicians to be precipitants of trauma symptoms in posttraumatic stress disorder (PTSD). Primitive brain systems involved in fear responsivity and survival also mediate smell, including the olfactory cortex and amygdala. The purpose of this study was to measure neural correlates of olfaction in PTSD. METHODS: We exposed male combat veterans with PTSD (N = 8) and without PTSD (N = 8) to a set of smells, including diesel (related to traumatic memories of combat), and three other types of smells: odorless air, vanilla/coconut, and hydrogen sulfide (H2S) (respectively, a neutral, positive, and negative hedonic nontraumatic smell) in conjunction with PET imaging of cerebral blood flow and assessment of psychophysiological and behavioral symptoms. All subjects also underwent a baseline of olfactory acuity. RESULTS: PTSD patients rated diesel as unpleasant and distressing, resulting in increased PTSD symptoms and anxiety in PTSD versus combat controls. Exposure to diesel resulted in an increase in regional blood flow (rCBF) in amygdala, insula, medial prefrontal cortex, and anterior cingulate cortex, and decreased rCBF in lateral prefrontal cortex in PTSD in comparison to combat controls. Combat controls showed less rCBF changes on any smell, and did not show amygdala activation upon diesel exposure. CONCLUSIONS: These data support the hypothesis that in PTSD trauma-related smells can serve as strong emotional reminders. The findings indicate the involvement of a neural circuitry that shares olfactory elements and memory processing regions when exposed to trauma-related stimuli. PMID- 17285096 TI - Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia. AB - OBJECTIVE: The objective of the current investigation was to determine the relationship between polymorphisms of the leptin system (leptin gene and leptin receptor) and olanzapine-induced weight gain in persons with schizophrenia. DESIGN: Pharmacogenetic association reanalysis of a longitudinal, open label, six week, fixed dose trial of olanzapine response and adverse effects. SUBJECTS: Thirty-seven males and females with clinically symptomatic schizophrenia (age, 23 52) meeting DSM-IV criteria. MEASUREMENTS: Baseline and endpoint weight, BMI, olanzapine dose, plasma levels, and psychopathology measures were completed in a prior study. These subjects were subsequently genotyped for the -1548 G/A polymorphism of the leptin gene and the Q223R polymorphism of the leptin receptor. The relationship between alleles at each locus, olanzapine plasma levels, and percent change in body mass index (BMI) from baseline were conducted. RESULTS: Genotypes and alleles for each locus were not individually associated with olanzapine-induced weight gain in this study population. Changes in BMI from baseline increased significantly in persons with olanzapine plamsa levels >20.6 ng/mL for subjects carrying at least one G allele at both candidate loci compared to those who did not have a G allele at each (P = 0.049). CONCLUSIONS: This study suggests that genetic variability in the leptin gene and leptin receptor may predispose some individuals to excessive weight gain from increased exposure to olanzapine. PMID- 17285097 TI - Citalopram versus amitriptyline in elderly depressed patients with or without mild cognitive dysfunction: a danish multicentre trial in general practice. AB - This double-blind, multicenter trial, carried out in general practice in Denmark, comprised 221 women and 70 men, aged 58 to 97 years, with major depression (with or without mild cognitive dysfunction) or dysthymia (DSM-III-R). Patients had a total score > or =13 on the 17-item Hamilton Depression Rating Scale (HDRS) and a score > or =20 on the Mini Mental State Examination scale. The efficacy and tolerability of citalopram (20-40 mg daily) and amitriptyline (50-100 mg daily) were compared over 12 weeks. The participating general practitioners were trained at corating sessions in the use of the HDRS and Melancholia Scale (MES) prior to and during the study. The inter-observer reliability was assessed to investigate if general practitioners were able to use scales that measure the severity of depression. The two treatments were considered equally effective; the 90% confidence interval for the difference between the treatment groups in change from baseline to end-point in HDRS total score (-0.84 to +1.23) was within the predefined interval (-4 to +4). Significantly more patients on citalopram (50%) than on amitriptyline (31%) reported no adverse events at all (P = .001). Moreover, patients on amitriptyline reported adverse events significantly earlier and more frequently than patients on citalopram. The inter-observer reliability was highly satisfactory, with intra-class correlation coefficients (ICC-U) of .83 for the HDRS and .82 for the MES; however, the ICC-U for the Clinical Global Impressions was .54, indicating a poorer consensus in the investigators clinical judgment. Training in the use of the HDRS and MES scales improved the inter observer reliability. PMID- 17285098 TI - Atypical antipsychotics and pituitary neoplasms in the WHO database. AB - Amisulpride and risperidone are potent dopamine D2 receptor blocking atypical antipsychotics that can cause hyperprolactinemia. Preclinical evidence shows that chronic administration of antipsychotics can cause pituitary adenomas in female mice. To investigate the clinical relevance in this finding, reports of pituitary neoplasms in the WHO adverse drug reaction (ADR) database were reviewed. Amisulpride and risperidone [corrected] had among the highest Information Component (IC) scores for benign pituitary neoplasm; amisulpride (IC = 3.31, IC025 = 1.83, 5 reports) and risperidone (IC = 4.03, IC025 = 3.33, 19 reports), and not otherwise specified (NOS) pituitary neoplasm: amisulpride (IC = 2.69, IC025 = 0.70, 3 reports) and risperidone (IC = 4.49, IC025 = 3.86, 23 reports). We conclude that there is a need for prospective studies to confirm causality and suggest that clinicians, until then, would consider a pituitary adenoma in patients experiencing severe hyperprolactinemia or associated symptoms when receiving potent D2 antagonists [corrected] PMID- 17285099 TI - Drug-drug interactions associated with second-generation antipsychotics: considerations for clinicians and patients. AB - OBJECTIVES: While not always clinically significant, patients with schizophrenia may be at risk for drug-drug interactions (DDIs) with second-generation antipsychotics. Second-generation antipsychotics are increasingly being used in a broader population of patients and, therefore, for those with comorbid illnesses, adjunctive treatments, or other diagnoses, the clinical significance of DDIs is increasing. This paper reviews currently available data concerning DDIs that occur between second generation antipsychotics, and other medications or substances, when metabolized by the cytochrome P-450 (CYP) family of enzymes. This review will assess the clinical relevance of these interactions for physicians and patients with schizophrenia. METHODS: EMBASE and MEDLINE searches were conducted (no date restrictions) using the keywords "drug-drug interactions," "atypical antipsychotics," "olanzapine," "ziprasidone," "quetiapine," "risperidone," "aripiprazole," "clozapine," "asenapine," "bifeprunox," and "paliperidone." PRINCIPAL OBSERVATIONS: Second-generation antipsychotics are primarily metabolized by CYP enzymes. When coadministered with inducers or inhibitors (psychotropic or non-psychotropic medications or substances) of CYP enzymes, antipsychotic plasma levels may be reduced or increased, respectively, as a result of DDIs. This can result in a reduced effectiveness of the antipsychotic, or an increased risk of adverse events, respectively. Drugs with a less clinically significant risk for DDIs are a more reliable treatment option for patients in whom drug plasma levels may fluctuate. CONCLUSION: Some of the currently available second-generation antipsychotics have a higher potential for DDIs. Agents with a reduced liability for DDIs may be safer treatments as the systemic drug concentration is less likely to seriously increase/decrease when other medications are knowingly or inadvertently co prescribed or hepatic problems and drug abuse is present. PMID- 17285100 TI - Current approaches to the pharmacologic treatment of anxiety disorders. AB - Despite their high prevalence, the anxiety disorders are underdiagnosed and undertreated. Benzodiazepines, once the first line of treatment, have been superceded by SSRIs as the treatment of choice. Preclinical studies, however, suggest that CRF antagonists and antagonists of nicotinic,glutamate,5-HT1A,and NK 1 receptors may have potential anxiolytic action. Preliminary data suggest that tiagabine, the only available SGRI, may also be beneficial in the anxiety disorders. Further research on these novel agents in anxiety disorders is needed. PMID- 17285101 TI - Pulmonary hypertension during lithium therapy: clinical case study. AB - The authors presented a case of pulmonary hypertension during lithium therapy, while she has been on lithium for 6 years. The patient developed pulmonary hypertension without a prior diagnosed cardiac and/or pulmonary disease. This is the first report of pulmonary hypertension in an adult patient during lithium therapy. PMID- 17285102 TI - Treatment refractory psychosis remitted upon treatment with continuous positive airway pressure: a case report. AB - INTRODUCTION: Patients refractory, or responding only partially, to antipsychotic drugs are common in clinical practise. Medical diseases can present with psychotic symptoms or add to a psychotic picture and should not be missed. We report on a patient with schizophrenia whose treatment refractory psychosis remitted upon treatment of her obesity-hypoventilation syndrome (OHS). CASE REPORT: A 63-year-old women previously diagnosed with hebephrenic schizophrenia developed treatment resistant auditory hallucinations along with extreme daytime fatigue and obesity. She was eventually diagnosed with Pickwickian syndrome or OHS and received treatment with continuous positive airway pressure (CPAP). Restoring the patient's alveolar hypoventilation with nocturnal CPAP led to the complete remission of hallucinations. DISCUSSION: We suggest that this case highlights an issue that might become more common in the future with increasing prevalence of overweight. Indeed, some atypical neuroleptics might even counteract their own therapeutic effect by inducing excessive weight gain that increases the risk for OHS. We recommend taking a careful sleep history in schizophrenic patients with obesity and to perform a polysomnography in suspect cases. PMID- 17285104 TI - Haemorrhagic stroke and vasculitic-like cerebral angiography in a patient with eosinophilic fasciitis. Case report. AB - Cerebral vasculitis is an uncommon cause of haemorrhagic stroke. A case of intracerebral haemorrhage in a patient with eosinophilic fasciitis, a rare scleroderma-like connective tissue disease, with a possible inflammatory involvement of cerebral vessels is reported. Pathogenetic mechanism of such association and diagnostic controversies are reviewed. PMID- 17285103 TI - Fibromylagia, chronic fatigue, and adult attention deficit hyperactivity disorder in the adult: a case study. AB - Adult attention deficit hyperactivity disorder (ADHD) may share common features with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). In an outpatient psychiatric clinic, a number of adult patients who presented primarily with symptoms of ADHD, predominately inattentive type, also reported unexplained fatigue, widespread musculoskeletal pain or a pre-existing diagnosis of CFS or FMS. As expected, ADHD pharmacotherapy usually attenuated the core ADHD symptoms of inattention, distractibility, hyperactivity, and impulsivity. Less expected was the observation that some patients also reported amelioration of pain and fatigue symptoms. The utility of ADHD medications in FMS and CFS states may be their innate arousal and enhanced filtering properties. This model supposes that FMS and CFS are central processing problems rather than peripheral disorders of muscles and joints. PMID- 17285105 TI - Oligodendroglial gliomatosis cerebri. Case report. AB - Gliomatosis cerebri of oligodendroglial origin is very unusual. In the present article we illustrate a case of this pathology, outlining his severity and suggesting it seems to be more aggressive than the astroglial type. We give a short focus about the diagnosis and the therapy of this neoplastic disease. PMID- 17285106 TI - Cerebellar abscess due to Rhodococcus equi in an immunocompetent patient: case report and literature review. AB - Rhodococcus equi (R. equi) is a facultative, intracellular, nonmotile, non-spore forming, gram-positive coccobacillus, primarily causes zoonotic infections that affect grazing animals, mainly horses and foals and is a rare opportunistic pathogen found in severely compromised patients, and most commonly in recent years, in human immunodeficiency virus (HIV)-infected persons. Early cases, most in patients receiving immunosuppressant therapy, were more likely to be successfully treated with antimicrobial agents than cases in AIDS patients, it is emerging as an important pathogen in patients with cellular immune deficiency. We report a case of an immunocompetent 37 year-old patient with cerebellar abscess location that seems to be the only thin to today described in the literature. R. equi is a facultative, intracellular, nonmotile, non-spore-forming, gram-positive coccobacillus, primarily causes zoonotic infections that affect grazing animals, mainly horses and foals and is a rare opportunistic pathogen found in severely compromised patients, and most commonly in recent years, in human immunodeficiency virus (HIV)-infected persons. Early cases, most in patients receiving immunosuppressant therapy, were more likely to be successfully treated with antimicrobial agents than cases in AIDS patients, it is emerging as an important pathogen in patients with cellular immune deficiency. We report a case of an immunocompetent 37 year-old patient with cerebellar abscess location that seems to be the only thin to today described in the literature. PMID- 17285107 TI - Zinc ribbon domain containing 1 protein: modulator of multidrug resistance, tumorigenesis and cell cycle. AB - Zinc ribbon domain containing 1 (ZNRD1) gene encoding a protein consisting of two zinc ribbon domains was recently cloned from the human HLA locus. So far, ZNRD1 has been found implicated in transcription regulation and might play potential roles in mediating several biological processes, including multidrug resistance, tumorigenesis and cell cycle. This article reviewed these recent findings and provided additional information to support the role of ZNRD1 gene as a novel candidate DNA damage repair related gene. PMID- 17285108 TI - MicroRNAs in normal and cancer cells: a new class of gene expression regulators. AB - MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at posttranscriptional level. They are involved in cellular development, differentiation, proliferation and apoptosis and play a significant role in cancer. This review describes miRNA biogenesis, their functions in normal cells, and alterations of miRNA sets in cancer and roles of antitumorigenic and oncogenic miRNAs in cancer development. PMID- 17285109 TI - The role of intercellular adhesion molecule-1 in head and neck cancer. AB - The intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin gene superfamily of adhesion molecules expressed in multiple human tissues and participating in various physiologic and pathophysiologic processes of the human body. The alterations in the expression of ICAM-1 in the various types of the cancer of the head and neck are discussed in this mini-review following the existing status from the current literature. Possible applications of this developing knowledge in the diagnosis and prognosis of head and neck cancer are briefly mentioned. PMID- 17285110 TI - Expression of adaptor protein Ruk/CIN85 isoforms in cell lines of various tissue origins and human melanoma. AB - AIM: Development of monoclonal and polyclonal antibodies against recombinant GST fused proteins including correspondingly N- and C-terminal parts of Ruk/CIN85 adaptor protein. Analysis of Ruk/CIN85 expression patterns in cell lines of various tissue origins and human melanoma. METHODS: Recombinant GST-fused fragments of Ruk/CIN85 were expressed in bacterial system and affinity purified. Monoclonal antibodies against SH3A domain of Ruk/CIN85 were produced using hybridoma technique. The specificity of generated antibodies was examined by ELISA. Polyclonal antibodies against C-terminal coiled-coil region of Ruk/CIN85 were affinity purified from serum of immunized rabbit. Expression patterns of Ruk/CIN85 isoforms and their subcellular localization in cell lines of various tissue origins and human melanoma samples were analyzed by immunoblotting, immunoprecipitation and immunofluorescence microcopy. RESULTS: Ruk/CIN85 is ubiquitously expressed SH3-containing adaptor/scaffold protein which plays important roles in signalling processes. N-terminal half of Ruk/CIN85 molecule, including three SH3 domains, and its C-terminal coiled-coil region were used as antigens to produce monoclonal and polyclonal antibodies, respectively. Hybridoma cell lines secreting monoclonal antibodies (mAbs) to SH3 fragment of Ruk/CIN85 were established. One of the mAbs was extensively characterized and designated as MISh-A1. It was shown that this mAb recognizes an epitope, which resides within first SH3A domain. Polyclonal anti-Ruks Abs affinity purified from serum of immunized rabbit specifically recognized main Ruk/CIN85 isoforms, both endogenous and recombinant, in lysates of HEK293 cells. Notably, produced Abs did not cross react with CD2AP, the member of the same family of adaptor/scaffold proteins. Multiple molecular forms of Ruk/CIN85 with apparent molecular weights of 130, 80 85, 70-75, 50-56, 34-40 and 29 kD were detected in cell lyzates of NIH3T3, Cos1, L1210, HEK293, Ramos, HeLa S3, MDCK, C6, A549 and U937 using anti-Ruk antibodies. Oligomerization between p85 and p50-56 forms of Ruk/CIN85 was revealed in C6 and NIH3T3 cells, but not in HeLa S3 and HEK293 cells by immunoprecipitation using MISh-A1 antibody following anti-Ruk Western-blot analysis. Using immunofluorescent microscopy and anti-Ruk antibodies, endogenous Ruk-variates were found mostly in cytoplasm of C6, NIH3T3, HEK293 cells and at lower level - in nuclei. CONCLUSION: Patterns of Ruk/CIN85 molecular forms expression are cell specific and determined by cellular context. Assembly of oligomeric complexes between p85 and p50-56 Ruk/CIN85 isoforms in C6 and NIH3T3 cells but not in HeLa S3 and HEK293 cells may reflect their specific biological roles in different cell lines. High level of full-length Rukl/CIN85 form expression was revealed in extracts of human melanoma samples. Abs described in this paper may prove useful in future studies of Ruk/CIN85 expression and function in normal and transformed cells. PMID- 17285111 TI - Establishment of serum protein pattern for screening colorectal cancer using SELDI-TOF-MS. AB - AIM: The purpose of this study is to develop a proteomic pattern for distinguishing individuals with colorectal cancer from healthy controls and monitoring micrometastasis using SELDI-TOF-MS. METHODS: A training set consisting of 63 patients with colorectal cancer, 20 patients with benign colorectal diseases and 26 healthy volunteers was used to develop a proteomic model that discriminated colorectal cancer effectively. The sensitivity and specificity of this model was validated by an independent test set. To explore serum proteins changed after operation, the protein profiles of 31 postoperative patients were compared with those of preoperative patients. We also analyzed protein profiles of patients with and without metastasis to monitor micrometastasis. RESULTS: Our study yielded a four-peak model (m/z: 3191.5, 3262.9, 3396.3 and 5334.4) that discriminated cancer from non-cancer samples with sensitivity of 90.3% and specificity of 95.7%. This model was validated in the test set with sensitivity of 87.5% and specificity of 93.8% which was significantly better than the combination use of CEA, CA199 and CA242 (sensitivity 62.4%) for early detection of colorectal cancer. Two peaks (m/z: 2753.8 and 4172.4) were found down regulated in postoperative samples comparing with preoperative samples. We also detected two proteins (m/z: 9184.4 and 9340.9) that can discriminate patients with primary colorectal cancer from metastatic colorectal cancer. CONCLUSIONS: The four-peak model and two peaks (m/z: 2753.8 and 4172.4) detected in this study have the potential for assistance in diagnostics and therapeutic strategies in colorectal cancer and the two proteins (m/z: 9184.4 and 9340.9) were effective biomarkers for monitoring micrometastasis. PMID- 17285112 TI - Regulated expression of human beta-defensin-2 leads to altered phenotype and growth patterns of cultured human embryonal kidney cells. AB - AIM: To create cell line with regulated expression of human beta-defensin-2 (hBD 2) and evaluate the influence of expressed peptide on its phenotypic and growth patterns. MATERIALS AND METHODS: Using cloning techniques, on the base of human embryonic kidney cells of HEK293T line, stable T-rex HEK-hBD2-m cell subline expressing mature biologically active hBD-2 molecule upon the presence of tetracycline in culture medium was generated. The morphological patterns, growth characteristics and colony forming activity of these cells were studied using routine techniques. RESULTS: T-rex HEK-HBD2-m cell subline was shown to express both mRNA and hBD-2m protein upon the presence of 1 mug/ml tetracycline in culture medium as it was demonstrated by RT-PCR and immunocytochemical approach. Upon prolonged expression of hBD-2, the cells acquired special features: they lost ability to grow in monolayer in vitro and to form colonies in soft agar, characteristic to parental HEK293T cells, but possess higher growth rate and longer survival in FBS-free medium than wild type cells. CONCLUSION: Expression of hBD-2 in T-rex HEK-HBD2-m cell subline results in specific biological consequences that favor cell survival. PMID- 17285113 TI - Antileukemic activity of sulfonamide conjugates of arabinosylcytosine. AB - AIM: Cytosine arabinoside is routinely used for treatment of leukemias and lymphomas. However, because of its extensive metabolic inactivation and limited activity in chemotherapy, new analogues of araC are being tested. The aim of this work was to synthetize two araC conjugates and evaluates their cytotoxic/antileukemic activity. METHODS: Synthesis of araC-sulfonamide conjugates A and B was performed in anhydrous conditions using cyclostyling and 5'-chlorocyclocytidine as starting material. Elemental analysis and NMR, IR and UV spectrometry were used for structure confirmation. The synthesized araC conjugates were tested for their cytotoxicity in L1210 leukemia cells in vitro and for therapeutic activity and toxicity in vivo in leukemia L1210-bearing mice. RESULTS: The cytotoxic activities of araC and two synthesized conjugates A and B were expressed as IC(50) (micromol/l) and were compared respectively. The conjugate A is 303-times less active and the conjugate B is 757-times less active than araC. Consequently, the antileukemic activity and the acute toxicity of these compounds were examined in experiments involving leukemia L1210-bearing mice. Statistically significant therapeutic outcome was observed when the dosage of both araC conjugates was increased 10-times compared to araC. Next, the ration of cytotoxicity vs therapeutic activity for araC and both conjugates was performed. It was recorded that the ration between cytotoxicity and therapeutic activity for araC is 3333, for the conjugate A and B, the ration is significantly lower (110 and 44). This indicates that the inactivation of araC conjugate A is 30-times slower and the inactivation of conjugate B is 75-times slower as araC inactivation. CONCLUSIONS: The differences in cytotoxic and therapeutic activity registered in araC treatment and between two araC-analogues are most probably caused by slow liberation of araC from both conjugates. We are considered that prolonged araC liberation protected them from inactivation and extended the time period of therapeutic action both araC conjugates. The obtained results can serve as stimuli for further investigation of new araC-analogues. PMID- 17285114 TI - Photodynamic efficacy of topical application of chlorin e6--polyvinyl pyrrolidone complex in tumor-bearing rats. AB - AIM: To evaluate the antitumor efficacy of photodynamic therapy with ointment form of chlorin e6--polyvinyl pyrrolidone complex. METHODS: 2 or 5% chlorin e6 ointment was applied on the surface of rat SM-1 tumor for 15 min-5 h, and then tumors were scored for photosensitizer accumulation and tissue damage induced by laser irradiation. RESULTS: Selectivity of chlorin e6 accumulation in tumor tissues considerably increases when photosensitizer was applied topically compared with intravenous administration. Antitumor efficacy of photodynamic therapy using topical application of chlorin e6--polyvinyl pyrrolidone complex is just as high as upon intravenous administration of the preparation. CONCLUSION: The level of tissue accumulation of chlorin e6--polyvinyl pyrrolidone complex administered in ointment form allows to carry out fluorescence diagnosis and PDT of superficially localized malignant tumors. PMID- 17285115 TI - The study of possibility to elevate antitumor activity and decrease of systemic toxic effects of cisplatin by its binding with deliganded albumin. AB - AIM: To evaluate antitumor and toxic action of cisplatin (CP) in non-bound form and in a complex with deliganded albumin. METHODS: To study complex-formation between CP and albumin, differential scanning and isothermic flow microcalorimetry were used. For quantitive evaluation of albumin-bound CP, the method of ultrafiltration was applied. Concentration of platinum in the samples was determined by atomic-absorption spectral analysis. Antitumor and toxic effect of CP and CP-albumin complex was studied in vivo using Guerin carcinoma (GC) model. RESULTS: It has been shown that the second drug-binding site, located in the III domain of albumin molecule is one of the main points of binding of CP. Purification of officinal human serum albumin (HSA) on highly active carbon hemosorbents of HSGD mark allows to obtain deliganded albumin (dHSA) with elevated complex-forming ability toward CP. Administration of CP-dHSA complex provides higher rate of GC growth inhibition, than that of CP, and the content of creatinine in blood plasma of GC-bearing rats increases by 15% versus 40% in the case of CP administration. CONCLUSION: The data obtained allow recommend application of CP-dHSA to complex for enhancement of antitumor action and decrease of toxic effects of cisplatin. PMID- 17285117 TI - Sensitivity of human lymphocytes to genotoxic effect of n-methyl-n-nitrosourea: possible relation to gynecological cancers. AB - The aim of this work is to study responses of PHA-stimulated and resting lymphocytes to methylating agent N-methyl-N-nitrosourea (MNU) and to compare sensitivity to this agent of healthy donor lymphocytes and lymphocytes from patients with gynecological cancers. METHODS: Cytotoxicity of MNU, apoptotic death of lymphocytes, was evaluated using two common tests--annexin V-FITC detection assay and live/dead double staining assay (nuclear morphological changes). Genotoxic effect of the agent was determined as delayed (secondary) DNA double strand breaks (DSBs) using neutral comet assay both conventional variant and modified for detection of bromodeoxyuridine-labelled comets, produced by proliferating lymphocytes only. RESULTS: Unstimulated lymphocytes were tolerant to geno- and cytotoxic effects of MNU. In contrast to resting cells, proliferating lymphocytes showed significant genotoxicity (p=0.0054) of MNU followed by increased apoptotic death of cells (p<0.05). Average number of secondary DSBs induced by MNU in lymphocytes from patients with gynecological cancers was about 4-fold less than that of lymphocytes of healthy donors. While lymphocytes from cancer patients did not change proliferative index in response to MNU, the agent decreased 2-fold proliferative indices of stimulated lymphocytes from healthy donors. CONCLUSION: There is a reverse association between geno- and cytotoxicity of MNU in stimulated lymphocytes and the presence of tumor. The relationship appears to be based on MMR-insufficiency in lymphocytes of the cancer patients. PMID- 17285116 TI - Enhancing effect of new biological response modifier sulfoethylated (1-->3)-beta D-glucan on antitumor activity of cyclophosphamide in the treatment of experimental murine leukoses. AB - AIM: One of the advanced methodologies of the tumor therapy is the application of the so-called biological response modifiers used for activation of the endogenous antitumor mechanisms and combined with classical cytotoxic agents. The aim of this work was the investigation of the effect of sulfoethylated (1-->3)-beta-D glucan (SEG) in the treatment of experimental murine leukoses in combination with cyclophosphamide (CPA) and its ability to modulate the activity of lysosomal enzymes in tumor tissues. MATERIALS AND METHODS: The solid forms of inoculated murine leukoses P388 and L1210/1 were transplantated to male DBA/2 mice. The therapy was performed by treating animals with CPA (Biokhimik, Saransk, Russia) alone or in combination with SEG (Institute of Chemistry, Slovak Academy of Sciences, Slovakia). CPA was administered in saline as a single intraperitoneal (ip) injection on the 10th day after tumor transplantation; SEG was administered to mice ip 3 days after tumor transplantation with the intervals in 3 days. The therapy effect was estimated by measuring of solid tumor volume. Activity of the cysteine proteases--cathepsins B and L--was measured fluorometrically using fluorescent substrates Z-Arg-Arg-MCA and Z-Phe-Arg-MCA (Sigma, USA), respectively. The apoptosis was estimated evaluating the number of cells with fragmented nuclei using optical microscope. RESULTS: It has been demonstrated that application SEG leads to inhibition of tumor growth and potentiates therapeutic action of CPA, especially at repeated administrations during the whole treatment/observation At addition of SEG, therapeutic effect of a one-half reduced dose of CPA is equal or higher than that of the full dose. Therapeutic action of CPA and SEG on the studied tumors is realized predominantly through induction of apoptosis and is accompanied by a substantial increase of the activity of cysteine proteases cathepsins B and L in tumor tissues. The highest cathepsin B and cathepsin L activity in tumor tissue accompanied with the strongest inhibition of tumor growth. It is suggested that this phenomenon is due to the infiltration of the macrophages rich in the named enzymes into the tumor, where they phagocytize the apoptotic cells and tissue debris. CONCLUSION: Utilization of this polysaccharide BRM, sulfoethylated (1-->3)-beta-D-glucan, might potentially enhance efficiency of antitumor therapy with standard cytostatics without a need of substantial increase of their dosage and hence avoiding their toxic side-effects. PMID- 17285118 TI - Serum interleukin-12 and interleukin-18 levels in patients with oesophageal squamous cell carcinoma. AB - Interleukin-12 (IL-12) and interleukin-18 (IL-18) play an important role as immunomodulatory factors in cancer pathogenesis. THE AIM of the study was analyze changes of serum IL-12 and IL-18 concentrations in oesophageal squamous cell carcinoma patients depending on the progression of cancer. MATERIALS AND METHODS: Blood samples were taken from 41 patients with oesophageal cancer: 5 women and 36 men, mean age 59+/-9 years. 23 patients had surgical resection of oesophagus with II and III tumor stage, 18 patients with IV stage of cancer progression were treated by palliative procedures. The control group included 15 healthy blood donors: 4 female and 11 males, mean age 41+/-6 years. The concentrations of IL-12 and IL-18 were determined by ELISA tests. RESULTS: Serum IL-12 and IL-18 amounts detected in blood of oesophageal cancer patients were significantly higher in comparison to control group (p<0.001). Serum IL-12 level was higher in patients with IV stage of the disease than in patients with II and III stages. Also serum IL-18 level was significantly higher in patients with IV stage in comparison to patients surgically treated (p<0.05). Statistically significant differences were found in concentrations of IL-18 according to clinicopathological parameters such as: stage of cancer progression, tumor depth, lymph node metastasis (p<0.05). CONCLUSIONS: Serum IL-12 and IL-18 levels are significantly higher in oesophageal cancer patients than in the healthy subjects. A relation between IL-18 content and cancer progression has been registered. PMID- 17285119 TI - High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels. AB - AIM: To study the relationship between the level of generation of reactive oxygen species (ROS) and nitric oxide (NO) and activity of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the vessels isolated from rectal tumors and Arteria rectalis superior. METHODS: EPR at the room temperature and 77 degrees K, Spin Traps technology and zymography in polyacrylamide gels were applied. RESULTS: In the vessels isolated from rectal tumors and Arteria rectalis superior high levels of ROS, NO and formation of complexes of NO with FeS-proteins at the sites of electron-transporting chain of mitochondria have been detected. High activities of MMP-2 and MMP-9 in vascular wall were also observed. The direct positive correlation between the rate of NO generation and formation of complexes of NO with FeS-proteins as well as between ROS and NO formation and MMPs activities have been revealed. CONCLUSION: Altered oxidative equilibrium in mitochondria of cells in vascular wall promotes formation of cell hypoxia and its autocatalytic potentiation accompanied with activation of MMPs. PMID- 17285120 TI - Blood viscosity in patients with diffuse large B cell non-Hodgkin's lymphoma. AB - The aim of the study was to evaluate blood viscosity as possible marker of disease progression in patients with newly diagnosed non-Hodgkin's lymphoma (NHL). METHODS: The viscosity of blood samples from 20 patients with newly diagnosed aggressive NHL (stage I, n=7; stage II, n=4; stage III, n=7; stage IV, n=2) was analyzed using Brookfield DV-II + (USA) machine. RESULTS: Blood viscosity in NHL patients (median: 5.5+/-1.46 miliPascal) inversely correlated with lactatdehydrogenase (LDH) level, international prognostic index (IPI) score, and stage (p=0.02, r=-0.51; p=0.03, r=-0.63; and p=0.04, r=-0.45, respectively) and positively correlated with hemoglobin level (p=0.02, r=0.65)). CONCLUSION: According to our data, blood viscosity may be considered as a follow up marker in NHL patients along with LDH level or sedimentation rate. PMID- 17285121 TI - Caspase-dependent and -independent suppression of apoptosis by monoHER in Doxorubicin treated cells. AB - Doxorubicin (DOX) is an antitumour agent for different types of cancer, but the dose-related cardiotoxicity limits its clinical use. To prevent this side effect we have developed the flavonoid monohydroxyethylrutoside (monoHER), a promising protective agent, which did not interfere with the antitumour activity of DOX. To obtain more insight in the mechanism underlying the selective protective effects of monoHER, we investigated whether monoHER (1 mM) affects DOX-induced apoptosis in neonatal rat cardiac myocytes (NeRCaMs), human endothelial cells (HUVECs) and the ovarian cancer cell lines A2780 and OVCAR-3. DOX-induced cell death was effectively reduced by monoHER in heart, endothelial and A2780 cells. OVCAR-3 cells were highly resistant to DOX-induced apoptosis. Experiments with the caspase-inhibitor zVAD-fmk showed that DOX-induced apoptosis was caspase dependent in HUVECs and A2780 cells, whereas caspase-independent mechanisms seem to be important in NeRCaMs. MonoHER suppressed DOX-dependent activation of the mitochondrial apoptotic pathway in normal and A2780 cells as illustrated by p53 accumulation and activation of caspase-9 and -3 cleavage. Thus, monoHER acts by suppressing the activation of molecular mechanisms that mediate either caspase dependent or -independent cell death. In light of the current work and our previous studies, the use of clinically achievable concentrations of monoHER has no influence on the antitumour activity of DOX whereas higher concentrations as used in the present study could influence the antitumour activity of DOX. PMID- 17285122 TI - Study of p53 gene alteration as a biomarker to evaluate the malignant risk of Lugol-unstained lesion with non-dysplasia in the oesophagus. AB - Mutations of the p53 gene are detected frequently in oesophageal dysplasia and cancer. It is unclear whether Lugol-unstained lesions (LULs) with non-dysplastic epithelium (NDE) are precursors of oesophageal squamous cell carcinoma (ESCC). To study the genetic alterations of NDE in the multistep process of oesophageal carcinogenesis, we determined the relationship between p53 mutations and LULs NDE. Videoendoscopy with Lugol staining was performed prospectively in 542 oesophageal cancer-free subjects. Lugol-unstained lesions were detected in 103 subjects (19%). A total of 255 samples, including 152 LULs (NDE, 137; dysplasia, 15) and 103 paired samples of normal staining epithelium, were obtained from 103 subjects. After extraction of DNA and polymerase chain reaction analysis, direct sequencing method was applied to detect mutations of the p53 gene. The p53 mutation was detected in five of 137 samples with LULs-NDE (4%) and in five of 15 samples with dysplasia (33%). A hotspot mutation was found in 20% of LULs-NDE with p53 mutation and in 40% of dysplasia with p53 mutation. In contrast, no p53 mutations were found in 103 paired NDE samples with normal Lugol staining. In biopsy samples from oesophageal cancer-free individuals, the p53 missense mutations containing a hotspot mutation were found in NDE, which was identified as an LUL. These findings suggest that some LULs-NDE may represent the earliest state of oesophageal squamous cell carcinoma in Japanese individuals. PMID- 17285123 TI - Magnesium intake and colorectal cancer risk in the Netherlands Cohort Study. AB - Energy-adjusted magnesium intake was nonsignificantly inversely related to risk of colorectal cancer (n=2328) in the Netherlands Cohort Study on Diet and Cancer that started in 1986 (n=58 279 men and 62 573 women). Statistically significant inverse trends in risk were observed in overweight subjects for colon and proximal colon cancer across increasing quintiles of magnesium uptake (P-trend, 0.05 and 0.02, respectively). Although an overall protective effect was not afforded, our results suggest an effect of magnesium in overweight subjects, possibly through decreasing insulin resistance. PMID- 17285125 TI - Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients. AB - Established clinico-pathological factors can place patients with breast cancer into good and poor prognostic categories, but even within these groups behaviour and response to treatment can differ. This study examined the value of cell cycle and apoptotic regulatory proteins in predicting behaviour in a poor prognostic group. A total of 165 patients, all of whom had died of breast cancer with duration of survival 12-127 months, median 38 months, were examined using immunohistochemistry for proliferation, apoptosis, p53, phosphorylated p53, p21, checkpoint kinase 2 (Chk2), bcl-2, bax, survivin and XIAP. All had received chemotherapy and/or hormonal therapy and were predominantly T2, node positive, grade III with only half oestrogen-receptor (ER) positive. High proliferation, phosphorylated p53, Chk2 and survivin expression correlated with grade III and lack of ER, whereas low proliferation, p21 and bcl-2 related to better grade and presence of ER. On univariate analysis grade, proliferation, phosphorylated p53, bcl-2, ER and survivin related to duration of survival. In multivariate analysis, grade (P=0.001) and survivin (P=0.005) were independent prognostic factors, grade III and presence of survivin relating to shorter survival. The latter was particularly for those patients receiving neoadjuvant therapy and adjuvant chemo- and hormonal therapy. The presence of the inhibitor of apoptosis protein survivin is a highly significant independent predictor of shorter duration of survival of patients with poor prognostic features, and merits investigation as a marker in other prognostic groups. PMID- 17285126 TI - Predictive genetic testing for BRCA1/2 in a UK clinical cohort: three-year follow up. AB - This prospective multicentre study assesses long-term impact of genetic testing for breast/ovarian cancer predisposition in a clinical cohort. Areas evaluated include risk management, distress and insurance problems 3 years post-testing. Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation. One hundred and ninety-three out of 285 (70% response) participants at nine UK clinical genetics centres completed assessments at 3 years: 80% female; 37% carriers of a BRCA1/2 mutation. In the 3 years, post-genetic testing carriers reported more risk management activities than non-carriers. Fifty-five per cent of female carriers opted for risk reducing surgery; 43% oophorectomy; and 34% mastectomy. Eighty-nine per cent had mammograms compared with 47% non-carriers. Thirty-six per cent non-carriers > or =50 years did not have a mammogram post test. Twenty-two per cent male carriers had colorectal and 44% prostate screening compared with 5 and 19% non-carriers respectively. Seven per cent carriers and 1% non-carriers developed cancer. Distress levels did not differ in carriers and non carriers at 3-year follow-up. Forty per cent of female carriers reported difficulties with life and/or health insurance. Given the return to pre-test levels of concern among female non-carriers at 3 years and a substantial minority not engaging in recommended screening, there appears to be a need to help some women understand the meaning of their genetic status. PMID- 17285127 TI - Sustained elevation of Epstein-Barr virus antibody levels preceding clinical onset of nasopharyngeal carcinoma. AB - We have monitored Epstein-Barr virus (EBV) IgA antibody levels of 39 nasopharyngeal carcinoma (NPC) cases for up to 15 years before clinical onset of NPC, and assessed preclinical serologic status of another 68 cases. Our results identify a serologic window preceding diagnosis when antibody levels are raised and sustained. This window can persist for as long as 10 years, with a mean duration estimated to as 37+/-28 months. Ninety-seven of these 107 NPC cases exhibited such a window. Cases that did not may reflect individual antibody response to EBV. Serologic screening at enrollment identified those cases who had already entered the window and became clinically manifested earlier (median=28 months) than those who entered the window after enrollment (median=90 months). The former account for 19 of 21 cases diagnosed within 2 years of screening. Nasopharyngeal carcinoma risk levels among seropositive subjects were also highest during this period. Both prediction rates and risk levels declined thereafter; cases detected at later times were composed of increasing proportions of individuals who entered the serological window after screening. Our findings establish EBV antibody as an early marker of NPC and suggest that repeated screening to monitor cases as they enter this window has considerable predictive value, with practical consequences for cancer treatment. PMID- 17285128 TI - A phase I and pharmacokinetic study of indisulam in combination with carboplatin. AB - Indisulam (E7070) is an anticancer agent that is currently being evaluated in phase II clinical studies. A significant reduction in glutathione synthetase and glutathione reductase transcripts by indisulam provided a molecular basis for its combination with platinum agents. Indisulam demonstrated high anti-tumour activity in various preclinical cancer models. The objectives of this study were (1) to determine the recommended dose of indisulam in combination with carboplatin in patients with solid tumours and (2) to evaluate the pharmacokinetics of the combination. Patients with solid tumours were treated with indisulam in combination with carboplatin. Indisulam (350, 500, or 600 mg m( 2)) was given as a 1-hour intravenous infusion on day 1 and carboplatin (5 or 6 mg min ml(-1)) as an intravenous infusion over 30 min on day 2 of a three-weekly cycle. Sixteen patients received study treatment and were eligible. Thrombocytopenia was the major dose limiting toxicity followed by neutropenia. Both drugs contributed to the myelosuppressive effect of the combination. Indisulam 500 mg m(-2) in combination with carboplatin 6 mg min ml(-1) was identified not to cause dose limiting toxicity, but a delay of re-treatment by 1 week was required regularly to allow recovery from myelosuppression. The recommended dose and schedule for an envisaged phase II study in patients with non-small cell lung cancer is indisulam 500 mg m(-2) in combination with carboplatin 6 mg min ml(-1) repeated four-weekly. Patients who do not experience severe thrombocytopenia at cycle 1 will be permitted to receive an escalated dose of indisulam of 600 mg m(-2) from cycle 2 onwards. PMID- 17285129 TI - Ovarian cancer risk in premenopausal and perimenopausal women treated with Tamoxifen: a case-control study. AB - As tamoxifen stimulates ovarian steroidogenesis in premenopausal women, induces ovulation and increases the incidence of benign ovarian cysts, there has been concern that it might also increase ovarian cancer risk in women treated premenopausally. In a national case-control study in Britain, treatment histories were collected for 158 cases of ovarian cancer after breast cancer diagnosed at ages under 55 years and 464 controls who had breast cancer at these ages without subsequent ovarian cancer. Risk of ovarian cancer was not raised for women overall who had taken tamoxifen (odds ratio (OR)=0.9, 95% confidence interval (CI) 0.6-1.3) or for those treated when premenopausal (OR=1.0, 95% CI 0.6-1.6) or perimenopausal (OR=0.7, 95% CI 0.2-2.4). There was also no relation of risk to daily dose, duration or cumulative dose of tamoxifen, or time since last use. There was, however, a significantly raised risk in relation to non-hormonal chemotherapy. The results suggest that tamoxifen treatment of premenopausal or perimenopausal women does not materially affect ovarian cancer risk, but that non hormonal chemotherapy might increase risk. PMID- 17285131 TI - Leukaemia stem cells: hit or miss? PMID- 17285132 TI - Malignant germ cell tumours of childhood: new associations of genomic imbalance. AB - Malignant germ cell tumours (MGCTs) of childhood are a rare group of neoplasms that comprise many histological subtypes and arise at numerous different sites. Genomic imbalances have been described in these tumours but, largely because of the paucity of cases reported in the literature, it is unclear how they relate to abnormalities in adult MGCTs and impact on potential systems for classifying GCTs. We have used metaphase-based comparative genomic hybridisation to analyse the largest series of paediatric MGCTs reported to date, representing 34 primary tumours (22 yolk sac tumours (YSTs), 11 germinomatous tumours and one metastatic embryonal carcinoma) occurring in children from birth to age 16, including 17 ovarian MGCTs. The large dataset enabled us to undertake statistical analysis, with the aim of identifying associations worthy of further investigation between patterns of genomic imbalance and clinicopathological parameters. The YSTs showed an increased frequency of 1p- (P=0.003), 3p+ (P=0.02), 4q- (P=0.07) and 6q- (P=0.004) compared to germinomatous tumours. Gain of 12p, which is invariably seen in adult MGCTs, was present in 53% of primary MGCTs of children aged 5-16 and was also observed in four of 14 YSTs affecting children less than 5. Two of these cases (14% of MGCTs in children less than 5) showed gain of the 12p11 locus considered to be particularly relevant in adult MGCTs. Gain of 12p showed a significant association with gain of 12q. Conversely, MGCTs without 12p gain displayed a significantly increased frequency of loss on 16p (P=0.04), suggesting that this imbalance may contribute to tumour development in such cases. This data provides new insight into the biology of this under-investigated tumour group and will direct future studies on the significance of specific genetic abnormalities. PMID- 17285133 TI - Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: cochrane review. AB - The published literature comparing surgery, with or without adjuvant endocrine therapy, with endocrine therapy alone in older women with operable breast cancer was systematically reviewed. The design used is Cochrane review. Randomised controlled trials retrieved from the Cochrane Breast Cancer Group Specialised Register on 29 June 2005. Eligible studies recruited women aged 70 years or over with operable breast cancer, fit for surgery under general anaesthia. The studies compared surgery (either mastectomy or wide local excision, with or without endocrine therapy) to endocrine therapy alone. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Double data extraction and quality assessment were undertaken. Seven eligible trials were identified of which six had published time-to-event data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen. When surgery alone was compared to endocrine therapy alone, there was no significant difference in OS (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.74-1.30, P=0.9), but a significant difference in PFS (HR 0.55, 95% CI 0.39-0.77, P=0.0006). When surgery with adjuvant endocrine therapy was compared to endocrine therapy alone, there was no significant difference in OS (HR 0.86, 95% CI 0.73-1.00, P=0.06), but a significant difference in PFS (HR 0.65 (95% CI 0.53-0.81, P=0.0001) for surgery plus endocrine therapy vs primary endocrine. The regimens have different side effect profiles with one study suggesting increased psychosocial morbidity at 3 months in the surgical arm, which resolves by 2 years. Primary endocrine therapy with tamoxifen is associated with inferior local disease control but non-inferior survival to surgery for breast cancer in older women. Trials are needed to evaluate appropriate selection criteria for its use in terms of patient co morbidity and quality of life. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for this population. PMID- 17285135 TI - A human cancer-associated truncation of MBD4 causes dominant negative impairment of DNA repair in colon cancer cells. AB - MBD4 binds to methylated DNA and acts as a thymine DNA glycosylase in base excision repair. Deficiency of MBD4 in mice enhances mutation at CpG sites and alters apoptosis in response to DNA damage, but does not increase tumorigenesis in mismatch repair-deficient mice. However, in humans, frameshift mutation of MBD4, rather than deletion, is what occurs in up to 43% of microsatellite unstable colon cancers. There is no murine equivalent of this mutation. We now show that recombinant truncated MBD4 (MBD4(tru)) inhibits glycosylase activities of normal MBD4 or Uracil DNA glycosylase in cell-free assays as a dominant negative effect. Furthermore, overexpression of MBD4(tru) in Big Blue (lacI) transfected, MSI human colorectal carcinoma cells doubled mutation frequency, indicating that the modest dominant negative effect on DNA repair can occur in living cells in short-term experiments. Intriguingly, the whole mutation spectrum was increased, not only at CpG sites, suggesting that truncated MBD4 has a more widespread effect on genomic stability. This demonstration of a dominant negative effect may be of significance in tumour progression and acquisition of drug resistance. PMID- 17285134 TI - Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer. AB - Cyclooxygenase-2 (COX-2) is associated with poor-prognosis breast cancer. We used a nude mouse xenograft model to determine the effects of COX-2 inhibition in breast cancer. Oestrogen receptor (ER)-positive MCF7/HER2-18 and ER-negative MDAMB231 breast cancer cell lines were injected into nude mice and allowed to form tumours. Mice then received either chow containing Celecoxib (a COX-2 inhibitor) or control and tumour growth measured. Tumour proliferation, apoptosis, COX-2, lymphangiogenesis and angiogenesis were assessed by immunohistochemistry (IHC), Western blotting or Q-PCR. Celecoxib inhibited median tumour growth in MCF7/HER2-18 (58.7%, P=0.029) and MDAMB231 (46.3%, P=0.0002) cell lines compared to control. Cyclooxygenase-2 expression decreased following Celecoxib treatment (MCF7/HER2-18 median control 65.3% vs treated 22.5%, P=0.0001). Celecoxib increased apoptosis in MCF7/HER2-18 tumours (TUNEL 0.52% control vs 0.73% treated, P=0.0004) via inactivation of AKT (median pAKT(ser473) 57.3% control vs 35.5% treated, P=0.0001--confirmed at Western blotting). Q-PCR demonstrated decreased podoplanin RNA (lymphangiogenesis marker) in the MCF7/HER2 18 - median 2.9 copies treated vs 66.6 control (P=0.05) and MDAMB231-treated groups--median 160.7 copies vs 0.05 control copies (P=0.015), confirmed at IHC. Cyclooxygenase-2 is associated with high levels of activated AKT(ser473) and lymphangiogenesis in breast cancer. Cyclooxygenase-2 inhibition decreases tumour growth, and may potentially decrease recurrence, by inactivating AKT and decreasing lymphangiogenesis. PMID- 17285136 TI - Treatment of 5-fluorouracil refractory metastatic colorectal cancer: an Australian population-based analysis. AB - Randomised trials have established the importance of oxaliplatin (O) and irinotecan (I) in advanced colorectal cancer (CRC). However, patients enrolled in clinical studies represent a restricted population and little is known about the use of O and I in the general population and the subsequent outcomes outside clinical studies. We used the Australian Health Insurance Commission (HIC) database to describe prescribing patterns of O and I and their impact on survival in all patients with 5-fluorouracil (5-FU) refractory CRC in Australia in 2002 and 2003. In 2999 patients, there was a marked increase in initial treatment with O rather than I; 48% of patients received O first in 2002 vs 66% in 2003 (P<0.001). Overall 40-45% of patients received both O and I; however, younger patients were more likely to receive both drugs (P<0.001). After 5-FU failure and treatment with O or I, the proportion of patients surviving 6 or 12 months was estimated to be 0.67 (95% CI, 0.66-0.69) and 0.42 (95% CI, 0.40-0.44), respectively. Survival was superior for patients who received both O and I; however, the sequence of agents had no impact. Older patients (> or =70 years) had inferior survival no matter which drug was used as initial treatment. Analysis of the Australian HIC database provides a valuable means of assessing patterns of use and outcomes of new therapies. PMID- 17285138 TI - Pseudo-hydrodynamic delivery of helper-dependent adenoviral vectors into non human primates for liver-directed gene therapy. AB - Helper-dependent adenoviral vectors (HDAds) are attractive for liver-directed gene therapy because they can mediate long-term, high-level transgene expression without chronic toxicity. However, systemic delivery requires high vector doses for efficient hepatic transduction, resulting in dose-dependent acute toxicity. Clearly, strategies to improve hepatic transduction with low vector doses are needed. In this regard, we have previously shown that hydrodynamic injection of helper-dependent adenoviral vectors into mice results in increased hepatic transduction, reduced systemic vector dissemination, and reduced pro-inflammatory cytokines compared with conventional injection and thus has the potential to improve dramatically the therapeutic index of helper-dependent adenoviral vectors. Unfortunately, the rapid, large-volume injection used in this method cannot be applied to larger animals. Therefore, we have developed a novel balloon occlusion catheter-based method to mimic hydrodynamic injection of helper dependent adenoviral vectors into non-human primates that does not require rapid, large-volume injection. Using a low, clinically relevant vector dose, this minimally invasive method results in high-efficiency hepatic transduction with minimal toxicity and stable long-term transgene expression for at least 413 days. PMID- 17285139 TI - Antisense oligonucleotide-induced exon skipping across the human dystrophin gene transcript. AB - Protein-truncating mutations in the dystrophin gene lead to the most common childhood form of muscle wasting, Duchenne muscular dystrophy. Becker muscular dystrophy, a condition that typically arises from dystrophin gene lesions that do not disrupt the reading frame, clearly indicates that substantial domains of the dystrophin protein are not essential. Potential therapeutic intervention exists during pre-mRNA splicing, whereby selected exons are excised to either remove nonsense mutations or restore the reading frame around frame-shifting mutations from the mature mRNA. Appropriately designed antisense oligonucleotides (AOs), directed at amenable splicing motifs across the dystrophin gene transcript, block exon recognition and/or spliceosome assembly so that targeted exons are removed from the mature mRNA. We describe a panel of AOs designed to induce skipping of every exon within the human dystrophin gene transcript, with the exception of the first and last exons. Every exon targeted in vitro could be removed from the dystrophin mRNA, although some exons are more efficiently excluded than others. No single motif has emerged as a universal AO annealing site for redirection of dystrophin pre-mRNA processing, although the general trend is that the most efficient compounds are directed at motifs in the first half of the target exon. PMID- 17285137 TI - A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR 214936) therapy in patients with advanced renal cell carcinoma. AB - In a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity. PMID- 17285140 TI - Real-time fluorescence tracking of dynamic transgene variegation in stem cells. AB - Transgene variegation is caused by epigenetic switching between expressing and silent states. gamma-retrovirus vectors can be variegated in stem cells, but the dynamics of epigenetic remodeling during transgene variegation are unknown. Here, we measured variegated enhanced green fluorescent protein gamma-retrovirus expression over 4 days in individual embryonic stem cells while tracking cells in order to create expression lineage trees: 56 colony founder cells and their progeny were tracked over seven generations. Nineteen lineages produced synchronized inheritable trajectories of transgene silencing or reactivation, indicative of epigenetic remodeling with long-term stable inheritance. Short-term fluctuations in fluorescence intensity were also observed, which contributed low amplitude variation to transgene expression level. These two processes have different frequencies and inheritability, but together contribute to variegated transgene expression. Inhibition of DNA methylation with 5-azacytidine eliminated long-term transgene silencing over 4 days, but short-term fluctuations continued. Our approach applies real-time imaging technology to track the long-term dynamics of transgene expression to investigate the timing and expression patterns leading to variegation. PMID- 17285141 TI - Polyethylenimine-complexed plasmid particles targeting focal adhesion kinase function as melanoma tumor therapeutics. AB - Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase implicated in cell cycle progression and cell migration. Overexpression of FAK in a variety of tumors has suggested that FAK is a promising target for therapeutic intervention. In this study, we took advantage of a modified polyethylenimine (M PEI) with high transfection efficiency for tumor cells and tissues, and targeted FAK function through both in vitro and in vivo approaches. The results demonstrated that both plasmid-encoded FAK small interfering RNA (siRNA) and overexpression of FAK-related non-kinase (FRNK, FAK dominant negative) dramatically inhibited in vitro B16F10 cell proliferation and invasion. We used two transplantable mouse tumor models of primary and metastatic melanoma to evaluate the therapeutic potential of PEI-complexed plasmids targeting FAK function. The results revealed that intratumoral delivery of PEI-complexed plasmids targeting FAK significantly suppressed primary tumor growth as well as metastasis of B16F10 cells into lung and lymph nodes. Both approaches prolonged the survival of the tumor-bearing mice. Taken together, these results indicate that intratumoral delivery of plasmid DNA targeting FAK function, using M-PEI as a gene carrier, represents a promising avenue for melanoma therapy. PMID- 17285142 TI - The +4G site in Kozak consensus is not related to the efficiency of translation initiation. AB - The optimal context for translation initiation in mammalian species is GCCRCCaugG (where R = purine and "aug" is the initiation codon), with the -3R and +4G being particularly important. The presence of +4G has been interpreted as necessary for efficient translation initiation. Accumulated experimental and bioinformatic evidence has suggested an alternative explanation based on amino acid constraint on the second codon, i.e., amino acid Ala or Gly are needed as the second amino acid in the nascent peptide for the cleavage of the initiator Met, and the consequent overuse of Ala and Gly codons (GCN and GGN) leads to the +4G consensus. I performed a critical test of these alternative hypotheses on +4G based on 34169 human protein-coding genes and published gene expression data. The result shows that the prevalence of +4G is not related to translation initiation. Among the five G-starting codons, only alanine codons (GCN), and glycine codons (GGN) to a much smaller extent, are overrepresented at the second codon, whereas the other three codons are not overrepresented. While highly expressed genes have more +4G than lowly expressed genes, the difference is caused by GCN and GGN codons at the second codon. These results are inconsistent with +4G being needed for efficient translation initiation, but consistent with the proposal of amino acid constraint hypothesis. PMID- 17285143 TI - Insights into the molecular evolution of the PDZ/LIM family and identification of a novel conserved protein motif. AB - The PDZ and LIM domain-containing protein family is encoded by a diverse group of genes whose phylogeny has currently not been analyzed. In mammals, ten genes are found that encode both a PDZ- and one or several LIM-domains. These genes are: ALP, RIL, Elfin (CLP36), Mystique, Enigma (LMP-1), Enigma homologue (ENH), ZASP (Cypher, Oracle), LMO7 and the two LIM domain kinases (LIMK1 and LIMK2). As conventional alignment and phylogenetic procedures of full-length sequences fell short of elucidating the evolutionary history of these genes, we started to analyze the PDZ and LIM domain sequences themselves. Using information from most sequenced eukaryotic lineages, our phylogenetic analysis is based on full-length cDNA-, EST-derived- and genomic- PDZ and LIM domain sequences of over 25 species, ranging from yeast to humans. Plant and protozoan homologs were not found. Our phylogenetic analysis identifies a number of domain duplication and rearrangement events, and shows a single convergent event during evolution of the PDZ/LIM family. Further, we describe the separation of the ALP and Enigma subfamilies in lower vertebrates and identify a novel consensus motif, which we call 'ALP-like motif' (AM). This motif is highly-conserved between ALP subfamily proteins of diverse organisms. We used here a combinatorial approach to define the relation of the PDZ and LIM domain encoding genes and to reconstruct their phylogeny. This analysis allowed us to classify the PDZ/LIM family and to suggest a meaningful model for the molecular evolution of the diverse gene architectures found in this multi-domain family. PMID- 17285144 TI - Biological designer self-assembling peptide nanofiber scaffolds significantly enhance osteoblast proliferation, differentiation and 3-D migration. AB - A class of self-assembling peptide nanofiber scaffolds has been shown to be an excellent biological material for 3-dimension cell culture and stimulating cell migration into the scaffold, as well as for repairing tissue defects in animals. We report here the development of several peptide nanofiber scaffolds designed specifically for osteoblasts. We designed one of the pure self-assembling peptide scaffolds RADA16-I through direct coupling to short biologically active motifs. The motifs included osteogenic growth peptide ALK (ALKRQGRTLYGF) bone-cell secreted-signal peptide, osteopontin cell adhesion motif DGR (DGRGDSVAYG) and 2 unit RGD binding sequence PGR (PRGDSGYRGDS). We made the new peptide scaffolds by mixing the pure RAD16 and designer-peptide solutions, and we examined the molecular integration of the mixed nanofiber scaffolds using AFM. Compared to pure RAD16 scaffold, we found that these designer peptide scaffolds significantly promoted mouse pre-osteoblast MC3T3-E1 cell proliferation. Moreover, alkaline phosphatase (ALP) activity and osteocalcin secretion, which are early and late markers for osteoblastic differentiation, were also significantly increased. We demonstrated that the designer, self-assembling peptide scaffolds promoted the proliferation and osteogenic differentiation of MC3T3-E1. Under the identical culture medium condition, confocal images unequivocally demonstrated that the designer PRG peptide scaffold stimulated cell migration into the 3-D scaffold. Our results suggest that these designer peptide scaffolds may be very useful for promoting bone tissue regeneration. PMID- 17285145 TI - Early respiratory management of respiratory distress syndrome in very preterm infants and bronchopulmonary dysplasia: a case-control study. AB - BACKGROUND: In the period immediately after birth, preterm infants are highly susceptible to lung injury. Early nasal continuous positive airway pressure (ENCPAP) is an attempt to avoid intubation and may minimize lung injury. In contrast, ENCPAP can fail, and at that time surfactant rescue can be less effective. OBJECTIVE: To compare the pulmonary clinical course and outcome of very preterm infants (gestational age 25-32 weeks) with respiratory distress syndrome (RDS) who started with ENCPAP and failed (ECF group), with a control group of infants matched for gestational age, who were directly intubated in the delivery room (DRI group). Primary outcome consisted of death during admission or bronchopulmonary dysplasia (BPD). RESULTS: 25 infants were included in the ECF group and 50 control infants matched for gestational age were included in the DRI group. Mean gestational age and birth weight in the ECF group were 29.7 weeks and 1,393 g and in the DRI group 29.1 weeks and 1,261 g (p = NS). The incidence of BPD was significantly lower in the ECF group than in the DRI group (4% vs. 35%; P<0.004; OR 12.6 (95% CI 1.6-101)). Neonatal mortality was similar in both groups (4%). The incidence of neonatal morbidities such as severe cerebral injury, patent ductus arteriosus, necrotizing enterocolitis and retinopathy of prematurity, was not significantly different between the two groups. CONCLUSION: A trial of ENCPAP at birth may reduce the incidence of BPD and does not seem to be detrimental in very preterm infants. Randomized controlled trials are needed to test whether early respiratory management of preterm infants with RDS plays an important role in the development of BPD. PMID- 17285146 TI - Niche occupation limits adaptive radiation in experimental microcosms. AB - Adaptive radiations have played a key role in the evolution of biological diversity. The breadth of adaptive radiation in an invading lineage is likely to be influenced by the availability of ecological niches, which will be determined to some extent by the diversity of the resident community. High resident diversity may result in existing ecological niches being filled, inhibiting subsequent adaptive radiation. Conversely, high resident diversity could result in the creation of novel ecological niches or an increase in within niche competition driving niche partitioning, thus promoting subsequent diversification. We tested the role of resident diversity on adaptive radiations in experimental populations of the bacterium Pseudomonas fluorescens that readily diversify into a range of niche specialists when grown in a heterogeneous environment. We allowed an undiversified strain to invade resident communities that varied in the number of niche specialists. The breadth of adaptive radiation attainable by an invading lineage decreased with increasing niche occupation of the resident community. Our results highlight the importance of niche occupation as a constraint on adaptive radiation. PMID- 17285148 TI - Great tits (Parus major) reduce caterpillar damage in commercial apple orchards. AB - Alternative ways to control caterpillar pests and reduce the use of pesticides in apple orchards are in the interest of the environment, farmers and the public. Great tits have already been shown to reduce damage under high caterpillar density when breeding in nest boxes in an experimental apple orchard. We tested whether this reduction also occurs under practical conditions of Integrated Pest Management (IPM), as well as Organic Farming (OF), by setting up an area with nest boxes while leaving a comparable area as a control within 12 commercial orchards. We showed that in IPM orchards, but not in OF orchards, in the areas with breeding great tits, apples had 50% of the caterpillar damage of the control areas. Offering nest boxes to attract insectivorous passerines in orchards can thus lead to more limited pesticide use, thereby adding to the natural biological diversity in an agricultural landscape, while also being economically profitable to the fruit growers. PMID- 17285149 TI - Lanthanum carbonate. AB - Controlling hyperphosphatemia in patients with chronic renal failure on renal dialysis is a major problem. None of the available calcium- or aluminum-based phosphate binders match the requirements for an ideal agent, each having its own limitations. The introduction of sevelamer hydrochloride represented a step change in management. Lanthanum carbonate is an alternative nonaluminium, noncalcium phosphate binder. Taken with food, it is well tolerated. It is poorly absorbed and does not require functioning kidneys to be removed from the body. There is no evidence from current studies that it accumulates to biologically significant levels in tissues, but despite the large numbers of patients included in clinical trials, experience with long-term dosing is limited and, as with every new drug used in this type of clinical setting, patients should be carefully monitored as experience with the drug increases. Lanthanum carbonate binds phosphate effectively across the physiological pH range of the upper gastrointestinal tract, and has no detrimental effect on calcium, vitamin D or parathyroid hormone metabolism. From the extensive trial data it seems that lanthanum carbonate is an effective and practical phosphate binder. Lanthanum carbonate and sevelamer are two new oral phosphate binding agents that with others currently in preclinical trials, such as stabilized polynuclear iron idroxide, could well represent a significant breakthrough in the management of hyperphosphatemia in patients with chronic renal failure in whom dietary phosphate restriction and cheaper oral phosphate binding agents prove unsatisfactory. Comparative trials and enhanced clinical experience are needed before the exact place of these competing and complementary therapies can be properly identified in patient management. PMID- 17285147 TI - A functional architecture of optic flow in the inferior parietal lobule of the behaving monkey. AB - The representation of navigational optic flow across the inferior parietal lobule was assessed using optical imaging of intrinsic signals in behaving monkeys. The exposed cortex, corresponding to the dorsal-most portion of areas 7a and dorsal prelunate (DP), was imaged in two hemispheres of two rhesus monkeys. The monkeys actively attended to changes in motion stimuli while fixating. Radial expansion and contraction, and rotation clockwise and counter-clockwise optic flow stimuli were presented concentric to the fixation point at two angles of gaze to assess the interrelationship between the eye position and optic flow signal. The cortical response depended upon the type of flow and was modulated by eye position. The optic flow selectivity was embedded in a patchy architecture within the gain field architecture. All four optic flow stimuli tested were represented in areas 7a and DP. The location of the patches varied across days. However the spatial periodicity of the patches remained constant across days at approximately 950 and 1100 microm for the two animals examined. These optical recordings agree with previous electrophysiological studies of area 7a, and provide new evidence for flow selectivity in DP and a fine scale description of its cortical topography. That the functional architectures for optic flow can change over time was unexpected. These and earlier results also from inferior parietal lobule support the inclusion of both static and dynamic functional architectures that define association cortical areas and ultimately support complex cognitive function. PMID- 17285150 TI - Sildenafil citrate for the treatment of pulmonary hypertension. AB - Pulmonary arterial hypertension is a progressive disease that has a high rate of mortality. For these reasons, early treatment is essential. Treatment choices for pulmonary arterial hypertension are limited by drug tolerability, drug cost and inconvenience associated with administration techniques and dosing schedules. Therefore, a therapy that provides oral dosing with limited side effects would prove useful in managing many patients. Sildenafil citrate, the first and highly publicized oral medication to receive approval from the U.S. Food and Drug Administration for erectile dysfunction, has recently been approved for treatment of pulmonary arterial hypertension. This review summarizes the normal physiology of the pulmonary vasculature, and the pathophysiology involved in pulmonary arterial hypertension and the role of sildenafil in its treatment. PMID- 17285152 TI - Interleukin-2 for the treatment of human immunodeficiency virus infection. AB - Notwithstanding the significant impact of highly active antiretroviral therapy (HAART) on human immunodeficiency virus (HIV)-associated morbidity and mortality, HAART-induced immune restitution is not complete. The potential utility of interleukin (IL)-2 to augment immune function has been extensively evaluated. Intravenous or subcutaneous IL-2 has been conclusively shown to induce significant increases in CD4 cell counts in HIV-infected patients, in particular when given concomitantly with HAART. Large randomized clinical trials are underway to investigate whether these CD4 cell increments will result in tangible clinical benefits. PMID- 17285151 TI - Impaired insulin signaling and the pathogenesis of Alzheimer's disease. AB - There is a growing interest in possible links between impaired insulin signaling and the pathogenesis of Alzheimer's disease. Insulin and insulin-signaling mechanisms are important for neuronal survival, and central nervous system neurodegeneration is associated with dysfunctional neuronal insulin receptors. This short review focuses on recent findings that many important components of Alzheimer's disease appear to stem from imbalances in insulin signaling intrinsic to the brain, rather than systemic insulin imbalances, and that treatments aimed at redressing insulin imbalances in the brain could be effective therapies. PMID- 17285155 TI - Environmental Forensics in the UK. PMID- 17285153 TI - Pharmacotherapy of post-traumatic stress disorder. AB - In the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, DSM-III-R and DSM-IV, the diagnosis of post-traumatic stress disorder (PTSD) requires the presence of three symptom clusters: re-experiencing, avoidance and hyperarousal. The selective serotonin reuptake inhibitors (SSRIs), in particular sertraline and paroxetine, have emerged as the treatment of choice for trauma victims experiencing these three symptom clusters. While not approved by the U.S. Food and Drug Administration, other pharmacological agents are often used, some for symptoms found in victims of early, chronic or extreme stress. Referred to as having type II trauma, complex PTSD, disorders of extreme stress and enduring personality change after catastrophic experience, these patients, with symptoms such as dissociation, somatization and self-injurious behavior, need to be recognized as suffering from a trauma-related disorder qualitatively different from that presently captured in the DSM-IV. In this paper we will refer to DSM IV's construct as simple PTSD (sPTSD); to complex PTSD/disorders of extreme stress as cPTSD/DES; and to both as PTSD. We will review existing evidence for the efficacy of SSRIs in treating sPTSD as well as different pharmacological interventions that are necessary for the treatment of cPTSD/DES. In addition, since both sPTSD and cPTSD/DES frequently coexist with other mental disorders, treatment of comorbid PTSD will be addressed. Finally, given that existing rating scales are not designed to measure symptoms of cPTSD/DES, we will describe the Symptoms of Trauma Scale (SOTS), designed to measure symptoms of both sPTSD and cPTSD. PMID- 17285156 TI - Trends analysis of ambient 8 hour ozone and precursor monitoring data in the south central U.S. AB - For the south central U.S., lower tropospheric ozone pollution has been a persistent and challenging problem. This paper provides long-term trends analyses of the ozone and precursor monitoring data collected over the past 20 years in four south central U.S. cities. The results of these analyses should be useful to air quality scientists, managers, planners, and modelers in assessing the effectiveness of ozone pollution control strategies being implemented or being planned for the future. Results of the data analyses show that all areas have monitored significant decreases in ozone and precursor concentrations over the past 20 years, especially in El Paso, Texas. Continuing challenges include the reduction of the percentage of time that monitors record 8 hour ozone concentrations over the U.S. 8 hour ozone standard, and the future control of highly reactive volatile organic compounds. PMID- 17285157 TI - Optimizing a GC-MS method for screening of Stachybotrys mycotoxins in indoor environments. AB - Presence of Stachybotrys chartarum in indoor environments has been linked to building-associated disease, however, the causative agents are unknown. Verrucarol (VER) and trichodermol (TRID) are hydrolysis products of some major S. chartarum mycotoxins, i.e. macrocyclic trichothecenes and trichodermin. We optimized gas chromatography-mass spectrometry (GC-MS) methods for detecting VER and TRID in S. chartarum-contaminated indoor environmental samples. Heptafluorobutyryl derivatives of both VER and TRID exhibited little MS fragmentation and gave much higher detection sensitivity (sub-picogram injected onto the GC column), both in GC-MS and GC-MSMS, than trimethylsilyl derivatives. Optimal detection sensitivity and specificity was achieved by combining chemical ionization and negative ion (NICI) detection with MSMS. With this method, VER and TRID were detected in building materials colonized by S. chartarum and TRID was demonstrated in dust settled in the breathing zone in a house where an inner wall was colonized. In summary, we have shown that NICI-GC-MSMS can be used to demonstrate mycotoxins in house dust in S. chartarum-contaminated dwellings. PMID- 17285158 TI - Reactivity, interactions and transport of trace elements, organic carbon and particulate material in a mountain range river system (Adour River, France). AB - The background levels, variability, partitioning and transport of eleven trace elements-Ag, Al, As, Cd, Co, Cr, Cu, Mn, Pb, Zn and U-were investigated in a mountain range river system (Adour River, France). This particular river system displayed a turbulent hydrodynamic regime, characterized by flash-transient discharge conditions leading to fast shifts in suspended particulate matter (SPM) concentrations as high as two orders of magnitude (12 to 600 mg l(-1)). The distribution of SPM was accurately predicted with a "hysteresis" transport model, indicating that about 75% of the annual solids load was exported within 20 to 40 days. Dissolved and particulate concentrations of most trace elements were low compared to their concentrations in other reference river systems expect for Pb and Cr, associated with historical anthropogenic activities. Although dissolved and particulate metal concentrations were steady for most elements during low and average discharge conditions, significant changes were observed with increasing river discharge. The changes in trace element concentrations in the two compartments was found to induce a partitioning anomaly referred to as the particulate concentration effect. This anomaly was significant for Cr, Mn, Pb, Zn, Cu and organic carbon (p < 0.03). The processes driving this anomaly were possibly linked to the modification and/or increase of colloidal organic and inorganic vectors, suggested by the significant increase of DOC (p < 0.001) and dissolved Al concentrations (p < 0.05) during flood conditions. A complementary process linked to the influence of coarse particles of low complexation capacity and transported mainly during high discharge may also effect trace element concentrations. Annual metal fluxes transported by this river system were estimated using the hysteresis SPM model with consideration of these fate processes. Metals in the Adour River system are primarily exported into the Bay of Biscay (Atlantic Ocean). PMID- 17285159 TI - Influence of feeding procedure on biomarkers in caged rainbow trout (Oncorhynchus mykiss) used in environmental monitoring. AB - Biomarkers in feral fish can be a useful tool for environmental monitoring of aquatic ecosystems. Drawbacks, however, are that suitable fish species are not always available and that natural variations can bias the results. An alternative strategy is to use farmed fish placed in cages. There is, however, still a risk that factors other than pollution level could have an impact on the biomarkers and the observed responses in the fish. The present study evaluates the effects of feeding procedure on biomarkers in caged fish. Two feeding rations (2% and 8% weekly feeding) have been examined for a large number of biomarkers in caged rainbow trout (Oncorhynchus mykiss). Significant effects of feeding rations were found on hepatic ethoxyresorufin-O-deethylase (EROD) and catalase activity, PAH metabolites in bile, plasma ion concentrations and the presence of immature red blood cells. The influence on EROD activity and PAH metabolites seems to be caused by elevated uptake of pollutants when feeding ratios are higher. The effects on other biochemical and physiological variables are more likely caused by stress due to insufficient feeding. According to these results, valid comparison of fish groups in environmental monitoring requires standardized feeding levels. PMID- 17285160 TI - Capillary microextraction for simultaneous analysis of multi-residual semivolatile organic compounds in water. AB - Capillary microextractor (CME) in combination with a gas chromatograph-mass spectrometer (GC-MS) was employed for the determination of trace priority hazardous substances in water. Three groups of semivolatile organic compounds (SVOCs), i.e., chlorinated hydrocarbons, pesticides and polycyclic aromatic hydrocarbons (PAHs), were simultaneously determined. SVOCs were extracted from 7 mL of water samples on a 100 cm commercial gas chromatographic column (0.32 mm id x film thickness 0.25 microm, HP-5 capillary column) and eluted with only 3 microL of acetonitrile. The extractant was analyzed by GC-MS in the selected ion monitoring mode. The method showed good linearity over the concentration range 10 ng L(-1) to 3.0 mg L(-1) with correlation coefficients (r) greater than 0.99 and low limits of detection ranged from 10 ng L(-1) to 1.0 mg L(-1). High recovery (more than 80%) was obtained with relative standard deviation less than 10%. The method was successfully applied for trace level analyses of SVOCs in water samples. PMID- 17285161 TI - Genotoxicity assessment of soils from wastewater irrigation areas and bioremediation sites using the Vicia faba root tip micronucleus assay. AB - Genotoxicity potential of soils taken from wastewater irrigation areas and bioremediation sites was assessed using the Vicia faba root tip micronucleus assay. Twenty five soils were tested, of which 8 were uncontaminated soils and taken as the control to examine the influence of soil properties; 6 soils were obtained from paddy rice fields with a history of long-term wastewater irrigation; 6 soils were obtained from bioremediation sites to examine effects of bioremediation; and 5 PAH-contaminated soils were used to examine methodological effects between direct soil exposure and exposure to aqueous soil extracts on micronuclei (MN) frequency ( per thousand) in the V. faba root tips. Results indicate that soil properties had no significant influences on MN frequencies (p > 0.05) when soil pH varied between 3.4 to 7.6 and organic carbon between 0.4% and 18.6%. The MN frequency measured in these control soils ranged from 1.6 per thousand to 5.8 per thousand. MN frequencies in soils from wastewater irrigation areas showed 2- to 48-fold increase as compared with the control. Soils from bioremediation sites showed a mixed picture: MN frequencies in some soils decreased after bioremediation, possibly due to detoxification; whereas in other cases remediated soils induced higher MN frequencies, suggesting that genotoxic substances might be produced during bioremediation. Exposure to aqueous soil extracts gave a higher MN frequency than direct exposure in 3 soils. However, the opposite was observed in the other two soils, suggesting that both exposure routes should be tested in case of negative results from one route. Data obtained from this study indicate that the MN assay is a sensitive assay suitable for evaluating genotoxicity of soils. PMID- 17285162 TI - Polycyclic aromatic hydrocarbons in clams Ruditapes decussatus (Linnaeus, 1758). AB - The concentration of sixteen individual polycyclic aromatic hydrocarbons (PAHs) was measured in the clam Ruditapes decussatus whole soft tissues from several places of the Ria Formosa lagoon (Portugal). Total PAH (tPAH) concentrations were higher in the summer (August) and winter (January) than in the other months and the distribution pattern of the individual PAHs was generally dominated by the 4 aromatic ring PAHs, followed by the 2 + 3 aromatic rings PAHs. Benzo[a]anthracene and acenaphthene were the most representative PAHs of the two fractions. Principal components analysis (PCA) revealed that, in the Ria Formosa, seasonal variations are more important than spatial variations, due to changes in PAH source. These sources ranged from petrogenic to pyrolytic or a mixture of both. The origin of clam PAHs was also assessed by partial least squares (PLS) analysis using nineteen different PAH signatures, taken from the literature. It was possible to identify boat traffic, especially in the summer, as one of the most relevant PAH sources to the Ria Formosa. The influence of boat traffic was revealed by several signatures including diesel soot, oil and weathered oil and a mixture of different individual PAHs usually found in harbour sediments. Other relevant sources included combustion of organic matter such as forest fires and diverse domestic activities, occurring mainly in the summer. Most of the clams were considered safe for human consumption, except for some point samples, which presented unusually high PAH concentrations, suggesting the need for a regular survey of PAHs in clam tissues. PMID- 17285163 TI - Polycyclic aromatic hydrocarbons in Dalian soils: distribution and toxicity assessment. AB - Concentrations of 15 polycyclic aromatic hydrocarbons (PAHs) were measured in surface soils collected from Dalian, China, for examination of distributions and composition profiles and their potential toxicity. The sum of 15 PAHs (SigmaPAHs) ranged from 190 to 8595 ng g(-1) dry weight, and showed an apparent urban suburban-rural gradient in both SigmaPAHs and composition profiles. Using hierarchical cluster analysis (HCA), the sampling sites were grouped into four clusters corresponding to traffic area, park/residential area, suburban and rural areas. The ratios of naphthalene (Nap) and fluorene (Fl) versus fluoranthene (Flu), pyrene (Pyr) and indeno(1,2,3-cd)pyrene (InP) in the four clusters provided evidence of local distillation. The diagnostic ratios indicated the prevalent PAH sources were petroleum combustion and coal combustion in Dalian, and a cross plot of diagnostic ratios distinguished the urban samples from suburban and rural ones. Toxic potency assessment of soil PAHs presented a good relationship with benzo(a)pyrene (BaP) levels, toxic equivalent concentrations based on BaP (TEQ(BaP)) and dioxin-like toxic equivalent concentrations (TEQ(TCDD)). The study highlights that BaP is a good indicator for assessing the potential toxicity of PAHs, and presents a promising toxicity assessment method for soil PAHs. PMID- 17285164 TI - Approaches to high throughput physical organic chemistry. AB - High throughput (HT) techniques are now extensively used for the synthesis of libraries of several thousands of compounds. More recently, HT methods began to be applied to other areas, such as physical organic chemistry. This has allowed for instance the development of tools for HT reaction assessment, HT kinetic and thermodynamic measurements, and physicochemical property profiling, using a broad set of analytical tools, ranging from mass spectrometry to image analysis based techniques. This article provides an overview of recent HT physical organic chemistry techniques. Special attention is given to the application of quantitative analytical constructs for HT monomer reactivity profiling and HT evaluation of Hammett parameters. PMID- 17285165 TI - Robust platform for de novo production of heterologous polyketides and nonribosomal peptides in Escherichia coli. AB - During the past decade, numerous gene clusters responsible for the biosynthesis of important natural products have been identified from a variety of organisms. Heterologous expression utilizing E. coli has been employed to provide proteins for mechanistic understanding and structural analyses. It was very recently shown that this system is also capable of de novo production of biologically active forms of heterologous nonribosomal peptides, echinomycin and triostin A, through the introduction of genes encoding modules responsible for their assembly into this model bacterial host. The superlative advantage of using E. coli as a heterologous host is the availability of a wealth of well-established molecular biological techniques for its genetic and metabolic manipulation. The platform described above which was developed in our laboratory is ideal for use in the production of metabolites found in marine and symbiotic bacteria that are not amenable to artificial cultivation. Development and tailoring of our system will allow for the design of these natural products and ultimately combinatorial yet rational modification of these compounds. This review focuses on the heterologous expression of biosynthetic gene clusters for the assembly of therapeutically potent compounds. PMID- 17285166 TI - Taking control of P1, P1' and double bond stereochemistry in the synthesis of Phe Phe (E)-alkene amide isostere dipeptidomimetics. AB - A protocol for the stereocontrolled independent preparation of both C-2 epimers of Phe-Phe trans-vinyl amide isostere dipeptidomimetics has been devised based on a Wittig-type reaction, in which two chiral building blocks were joined with excellent E-selectivity to give compounds of the type PhePsi[(E)-CH[double bond, length as m-dash]CH]-PheOH. PMID- 17285167 TI - An enantioselective Bronsted acid catalyzed enamine Mannich reaction. AB - An enantioselective Bronsted acid catalyzed Mannich reaction between acetophenone derived enamines and N-Boc imines has been developed. Simple diol (S)-H(8)-BINOL has been identified as the optimal catalyst, to afford versatile beta-amino aryl ketones in good yield and enantiomeric excess. PMID- 17285168 TI - Water gelation abilities of alkylbenzyltriazole-appended 2'-deoxyribonucleoside and ribonucleoside. AB - Alkylbenzyltriazole units covalently bonded onto uridine nucleosides were synthesized and their suitability for water gelation compared with 2' deoxyuridine derivatives was tested. PMID- 17285169 TI - The synthesis of 1-thia-6-oxa-6alambda(4)-seleno-3-azapentalene and a 3H-1,2,4 dithiazole. AB - The reaction of thiocarbamoyl isoselenocyanate with a carbanion gave 1-thia-6-oxa 6alambda(4)-seleno-3-azapentalene, which has a hypervalent selenium, as the major product. The by-products 3-diacylmethylidene-5-dimethylamino-3H-1,2,4-dithiazole and thiocarbamate thioanhydride were also formed. PMID- 17285170 TI - Three-dimensional structure of HIV-1 VIF constructed by comparative modeling and the function characterization analyzed by molecular dynamics simulation. AB - VIF is one of the six accessory proteins of HIV-1. It has been shown to be necessary for the survival of HIV-1 in the human body and for the retention of viral infectivity. It is strongly expected that a new therapeutic strategy against HIV-1 infection could be realized by blocking the biological pathway to VIF. In this paper, a three-dimensional model of VIF was constructed by comparative modeling based on two templates, VHL and NarL, which were used to construct the C-terminal domain and N-terminal domain of VIF, respectively. A model of the VIF-ElonginB-ElonginC complex was constructed, and molecular dynamics simulations were used to investigate the interactions between VIF and ElonginB-ElonginC. Mutagenesis was used to identify the function of some conserved residues in the putative SOCS-box. The results showed that the mutations of the critical residues led to the disruption of the interactions between VIF and ElonginB-ElonginC, consistent with experimental observations. These novel models of VIF and its complex has therefore provided structural information for investigating the function of VIF at the molecular level. PMID- 17285171 TI - Synthesis and biological evaluation of nucleoside dicarboxylates as potential mimics of nucleoside diphosphates. AB - A series of nucleotide analogues wherein the diphosphate moiety has been replaced by a dicarboxylate were synthesized and tested for inhibitory activity against nucleoside diphosphate (NDP) kinase as well as several pathogenic bacterial strains. PMID- 17285172 TI - Marked small molecule libraries: a truncated approach to molecular probe design. AB - A truncated approach to the design of molecular probes from small molecule libraries is outlined, based upon the incorporation of a bioorthogonal marker. The applicability of this strategy to small molecule chemical genetics screens has been demonstrated using analogues of the known stress activated protein kinase (SAPK) pathway activator, anisomycin. Compounds marked with a propargyl group have shown activation of the SAPK pathways comparable to that induced by their parent structures, as demonstrated by immunoblot assays against the downstream target JNK1/2. The considerable advantages of this new approach to molecular probe design have been illustrated through the rapid development of a functionally active fluorescent molecular probe, through coupling of the marked analogues to fluorescent azides using the copper(i)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. Active molecular probes generated in this study were used to investigate cellular uptake through FACS analysis and confocal microscopy. PMID- 17285173 TI - AAPH-mediated antioxidant reactions of secoisolariciresinol and SDG. AB - Secoisolariciresinol (SECO ) is the major lignan found in flaxseed (Linum usitatissimum L.) and is present in a polymer that contains secoisolariciresinol diglucoside (SDG ). SECO, SDG and the polymer are known to have a number of health benefits, including reduction of serum cholesterol levels, delay in the onset of type II diabetes and decreased formation of breast, prostate and colon cancers. The health benefits of SECO and SDG may be partially attributed to their antioxidant properties. To better understand their antioxidant properties, SECO and SDG were oxidized using 2,2'-azobis(2-amidinopropane), an in vitro model of radical scavenging. The major lignan radical-scavenging oxidation products and their formation over time were determined. SDG was converted to four major products, which were the result of a phenoxyl radical intermediate. One of these products, a dimer of SDG, decomposed under the reaction conditions to form two of the other major products, and . SECO was converted to five major products, two of which were also the result of a phenoxyl radical intermediate. The remaining products were the result of an unexpected alkoxyl radical intermediate. The phenol oxidation products were stable under the reaction conditions, whereas two of the alcohol oxidation products decomposed. In general, only one phenol group on the lignans was oxidized, suggesting that the number of phenols per molecule may not predict radical scavenging antioxidant ability of lignans. Finally, SECO is a superior antioxidant to SDG, and it may be that the additional alcohol oxidation pathway contributes to its greater antioxidant ability. PMID- 17285174 TI - Synthesis and biological activities of novel furo[2,3,4-jk][2]benzazepin-4(3H) one derivatives. AB - A novel seven-membered lactam formation method has been established by intramolecular ring closure reaction of 4-bromo-(E)-3-[(2 alkylvinyl)carbonylamino]benzo[b]furans under Heck coupling conditions. A number of furo[2,3,4-jk][2]benzazepin-4(3H)-ones, tricyclicbenzo[b]furans, have been prepared by this method and evaluated for their leukotriene B(4) (LTB(4)) receptor and poly(ADP-ribose)polymerase-1 (PARP-1) inhibitory activities. PMID- 17285175 TI - The synthesis of phosphopeptides via the Bpoc-based approach. AB - The 2-(p-biphenylyl)-2-propyloxycarbonyl (Bpoc) group was examined as an N(alpha) protecting group in the stepwise assembly of the MAP Kinase ERK2 [178-188; Thr(P)(183), Tyr(P)(185)] peptide. The mild acid deprotection of the Bpoc group permitted (i) incorporation of a fully protected phosphothreonyl derivative and (ii) a TFA-based final cleavage step. The first five C-terminal residues (184 188) were incorporated in the Fmoc mode of peptide synthesis, with all subsequent amino acids coupled as their Bpoc-Xxx-OH derivatives. The target product was obtained in high purity and yield, indicating that a Bpoc-based approach to phosphopeptide synthesis was compatible with both the acid-labile side chain protecting groups employed and Hmp-Wang resin. PMID- 17285176 TI - Efficient Heck reactions catalyzed by a highly recyclable palladium(II) complex of a pyridyl-functionalized imidazolium-based ionic liquid. AB - The reactions of 2-(2-pyridyl)imidazole with alkyl iodides at 25 degrees C in the presence of base gave rise to 1-alkyl-2-(2-pyridyl)imidazole. Subsequent neat reactions with alkyl or polyfluoroalkyl halides at 100 degrees C, followed by anion exchange with LiN(SO(2)CF(3))(2), generated the mono-quaternary ionic liquids. All of them have excellent thermal stability and wide liquid range. Most of the salts with asymmetric N-substituents are liquid at room temperature. The effect of N-substituent variation and symmetry on NMR, TGA and DSC is discussed. Reaction of with palladium(II) chloride produced a mononuclear palladium ionic liquid complex, the structure of which was confirmed by single-crystal X-ray diffraction analysis. The Heck cross-coupling reactions using in ionic liquid demonstrated excellent stability and recyclability. PMID- 17285177 TI - An investigation of the reduction in aqueous acetonitrile of 4 methoxybenzenediazonium ion by the tetrakis(acetonitrile)Cu(I) cation catalysed by hydrogenphosphate dianion. AB - In aqueous acetonitrile containing a phosphate buffer, 4-methoxybenzenediazonium ion is reduced by one or more of the partially aquated cations derived from tetrakis(acetonitrile)Cu(I) cation in this medium. Investigation of the reaction mechanism indicates the rate determining step to be the association of the diazonium ion with the hydrogenphosphate dianion to give an adduct which then undergoes reduction by Cu(I). The reaction gives a range of products which have been identified and quantified by GC. One of these, 4-methoxyphenol was unexpected in the reducing conditions; its presence could be explained by the disproportionation of a 4-methoxyphenylcopper(II) complex giving bis(4 methoxyphenyl)copper(III) which reacts with water to produce the phenol and an equivalent amount of methoxybenzene. A scheme is proposed which accounts for all the observed products and computer modelling gives a satisfactory description of the distributions of the five major products as functions of the relative proportions of the reactants for dilute conditions and those where the reductant is in excess. When the diazonium ion is in excess, the behaviour of the model and the experimental reactant accountability suggest the occurrence of additional reactions which give products unobserved by GC. PMID- 17285178 TI - Solvent-free iodination of organic molecules using the I(2)/urea-H(2)O(2) reagent system. AB - Introduction of iodine under solvent-free conditions into several aromatic compounds activated toward electrophilic functionalization was found to proceed efficiently using elemental iodine in the presence of a solid oxidizer, the urea H(2)O(2) (UHP) adduct. Two types of iodo-functionalization through an electrophilic process were observed: iodination of an aromatic ring, and side chain iodo-functionalization in the case of arylalkyl ketones. Two reaction routes were established based on the required substrate : iodine : oxidizer ratio for the most efficient iodo-transformation, and the role of UHP was elucidated in each route. The first, requiring a 1 : 0.5 : 0.6 stoichiometric ratio of substrate to iodine to UHP, followed the atom economy concept in regard to iodine and was valid in the case of aniline, 4-t-Bu-phenol, 1,2-dimethoxy benzene, 1,3 dimethoxy benzene, 1,2,3-trimethoxy benzene, 1,2,4-trimethoxy benzene, 1,3,5 trimethoxy benzene, 1-indanone and 1-tetralone. The second reaction route, where a 1 : 1 : 1 stoichiometric ratio of substrate : I(2) : UHP was needed for efficient iodination, was suitable for side-chain iodo-functionalization of acetophenone and methoxy-substituted acetophenones. Moreover, addition of iodine to 1-octene and some phenylacetylenic derivatives was found to proceed efficiently without the presence of any oxidizer and solvent at room temperature. PMID- 17285179 TI - Of rehabilitation medicine and the rehabilitation physician. PMID- 17285180 TI - Results from a prospective acute inpatient rehabilitation database: clinical characteristics and functional outcomes using the Functional Independence Measure. AB - INTRODUCTION: Rehabilitation improves functional outcomes, but there is little data on the profiles and outcomes of patients undergoing inpatient rehabilitation in Singapore. The aims of this paper were to document the clinical characteristics and functional outcomes, using the Functional Independence Measure (FIM), of all patients admitted to an inpatient rehabilitation unit in a tertiary teaching hospital, and to identify and analyse factors significantly associated with better discharge functional scores and higher functional gains. MATERIALS AND METHODS: In this prospective cohort study over a 4-year period, clinical and functional data for 1502 patients admitted consecutively to the Singapore General Hospital inpatient rehabilitation unit were charted into a custom-designed rehabilitation database. The primary outcome measures were the discharge total FIM scores, FIM gain and FIM efficiency. Multiple linear regression analysis was used to identify independent variables associated with better discharge FIM scores and FIM gain. RESULTS: The mean age was 61.3 +/- 15.0 years and 57.2% of the patients were male. Stroke (57.9%) followed by spinal cord injury (9.7%) were the most common diagnoses. The average rehabilitation length of stay was 21.5 +/- 19.0 days. The mean admission total FIM score was 70.3 +/- 23.2 and the mean discharge total FIM score was 87.3 +/- 23.0, with this gain being highly significant (P <0.001). The mean FIM gain was 17.0 +/- 13.4 and FIM efficiency was 0.95 +/- 0.90 points/day. Factors associated with better functional outcomes were higher admission motor and cognitive FIM scores, male gender, a longer rehabilitation length of stay and the use of acupuncture. Factors associated with poorer functional outcomes were older age, clinical deconditioning, ischaemic heart disease, depression, pressure sores and the presence of a domestic worker as a caregiver. CONCLUSIONS: The FIM is an easy-to use, standardised and robust general measure of functional disability. Multiple demographic, clinical and socio-cultural variables are associated with the primary functional outcomes and should be taken into account in rehabilitation and discharge planning. Nevertheless, rehabilitation improves functional outcomes across a wide range of diagnoses. Further research should be aimed at evaluating long-term disability postdischarge from inpatient rehabilitation and translating these findings into improving rehabilitation and healthcare resource utilisation. PMID- 17285181 TI - Botulinum toxin type A for refractory neurogenic detrusor overactivity in spinal cord injured patients in Singapore. AB - INTRODUCTION: Managing neurogenic detrusor overactivity (NDO) successfully in spinal cord-injured patients is a challenge. The aims of preserving kidney function by achieving safe bladder pressures with anticholinergic medication often leave a significant proportion of patients with side effects. Botulinum toxin type A has been shown to be a promising alternative. MATERIALS AND METHODS: Spinal cord injury patients who had NDO, on clean intermittent self catheterisation, and were refractory to oral medications, were recruited. Three hundred units of botulinum toxin type A (Botox) in 30 mL NaCl solution were injected under cystoscopic guidance into the bladder. RESULTS: Fifteen patients were recruited of whom 9 were tetraplegic and 6 were paraplegic. Eleven (73.3%) had complete injuries. There was a significant reduction in the mean number of leakages from 3.75 +/- 1.79 pre-injection to 0.67 +/- 1.31 and 1.5 +/- 1.5 at 6 and 26 weeks postinjection, respectively (P <0.05). Seventy-five per cent, 37.5% and 50% were completely dry at 6, 26 and 39 weeks post-injection, respectively. The mean maximal catheterisable volume increased from 312.3 +/- 145.6 mL pre injection to 484.6 +/- 190 mL, 422.3 +/- 157.3 mL and 490.0 +/- 230.4 mL at 6, 26 and 39 weeks post-injection, respectively (P <0.005). Maximum detrusor pressure decreased significantly from 66.3 +/- 22.6 cmH2O to 21.2 +/- 23.1 cmH2O and 33.6 +/- 30.2 cmH2O at 6 and 26 weeks post-injection, respectively (P <0.05). The volume at which reflex detrusor contractions first occurred increased from 127.8 +/- 57.5 mL pre-injury to 305.7 +/- 130.8 mL at 6 weeks and 288.3 +/- 13.0 mL at 26 weeks post-injection (P <0.05). Mean cysometric bladder capacity increased from 187.8 +/- 69.2 mL to 305 +/- 136.4 mL and 288.3 +/- 13.0 mL at 6 and 26 weeks post-injury, respectively (P <0.05). Sixty per cent of patients were completely off medications at 6 and 26 weeks post-injection. One patient had urinary tract infection and 1 experienced autonomic dysreflexia during cystoscopy. Satisfaction levels increased from 4.3 +/- 2.3 pre-injury to 7.2 +/- 1.9 and 7.3 +/- 2.3 at 6 weeks and 26 weeks, respectively. This also correlated with fewer leakages. CONCLUSION: Botulinum toxin type A injected into the detrusor is safe and efficacious for spinal cord injured patients with refractory detrusor overactivity. This effect is maintained at 26 weeks post-injection. PMID- 17285182 TI - Employment status six months after discharge from inpatient rehabilitation for a mild-to-moderate physical disability. AB - INTRODUCTION: Physical disability presents unique challenges to the individual, family and community. One of these challenges is returning the individual to work. The current study looks at individuals with a mild-to-moderate physical disability 6 months post-discharge from inpatient rehabilitation and their employment status and perceived barriers to returning to work. MATERIALS AND METHODS: Prospective study of consecutive Singaporean patients, aged 21 to 65 years, discharged from the acute inpatient Rehabilitation Medicine Service at Changi General Hospital with a mild-to-moderate physical disability, as determined by discharge Modified Barthel Index score, and their employment status 6 months after discharge. RESULTS: There were 68 patients who met the study criteria; of these, 31 (45.6%) were successfully employed by 6 months post discharge from inpatient rehabilitation. There was a statistically significant difference (P = 0.0004) between the 2 groups based on gender, with more males likely not to return to work as compared to their female counterparts. CONCLUSION: In this small prospective study, males were more likely not to return to work than females. Those of slightly younger age with more advanced education were more likely to return to work and fear of worsening of physical disability was the most common reason cited for not returning to work after a mild-to moderate physical disability. PMID- 17285183 TI - Botulinum toxin for post-stroke spastic hypertonia: a review of its efficacy and application in clinical practice. AB - Botulinum toxins (BTX) have revolutionised the management of focal post-stroke spastic hypertonia. Published literature has supported the efficacy and safety of BTX in reducing spastic hypertonia but has not convincingly demonstrated the ability to enhance function. While clinicians and stroke survivors have reported impressive clinical outcomes, randomised, controlled trials (RCTs), have demonstrated only significant improvement in muscle tone but not functional changes. This paper will review the evidence supporting the efficacy of BTX for spastic hypertonia and discuss current clinical practice. PMID- 17285184 TI - A brief review of traumatic brain injury rehabilitation. AB - INTRODUCTION: This article aims to provide an overview of the epidemiology, medical and rehabilitation issues, current evidence for traumatic brain injury (TBI) rehabilitation, recent advances and emerging practices. Special TBI population groups will also be addressed. MATERIALS AND METHODS: We included publications indexed in Medline and the Cochrane Database of Systemic Reviews from 1974 to 2006, relevant chapters in major rehabilitation texts and Physical Medicine and Rehabilitation Clinics of North America and accessed Internet publications. RESULTS: TBI has been implicated by the World Health Organisation to be a 21st century epidemic similar to malaria and HIV/AIDS, not restricted to the developed world. One third of patients may suffer severe TBI with long-term cognitive and behavioural disabilities. Injuries to the brain do not only damage the cerebrum but may give rise to a multisystem disorder due to associated injuries in 20% of cases, which can include complex neurological impairments, neuroendocrine and neuromedical complications. There is promising evidence of improved outcome and functional benefits with early induction into a transdisciplinary brain injury rehabilitation programme. However, TBI research is fraught with difficulties because of an intrinsically heterogeneous population due to age, injury severity and type, functional outcome measures and small samples. Recent advances in TBI rehabilitation include task-specific training of cognitive deficits, computer-aided cognitive remediation and visual-spatial and visual scanning techniques and body weight-supported treadmill training for motor deficits. In addition, special rehabilitation issues for mild TBI, TBI-related vegetative states, elderly and young TBI, ethical issues and local data will also be discussed. PMID- 17285185 TI - Myofascial pain--an overview. AB - Skeletal muscle is the largest organ in the human body. Any of these muscles may develop pain and dysfunction. In modern society, myofascial pain is a major cause of morbidity. It may present as regional musculoskeletal pain, as neck or back pain mimicking radiculopathy. It may also present as shoulder pain with concomitant capsulitis, and hip or knee pain with concomitant osteoarthritis. The condition is treatable. However, it is often under-diagnosed and hence undertreated. Traditional medical training and management of musculoskeletal pain have focused much attention on bones, joints and nerves. This review will focus on muscles, myofascial pain and dysfunction. During history taking and physical examination, precipitating and perpetuating factors, taut bands, trigger points, tender spots and sensitised spinal segments have to be accurately located and correctly identified for effective needling treatment. There is also a high recurrence rate unless appropriate exercises are prescribed, with active participation from the patient, to restore flexibility and balance to the muscles. With rehabilitation, many patients do not have to continue to suffer unnecessary pain that affects their daily activities and quality of life. Early diagnosis and management may also help reduce psychosocial complications and financial burden of chronic pain syndrome. PMID- 17285186 TI - Recovery and regeneration after spinal cord injury: a review and summary of recent literature. AB - INTRODUCTION: Spinal cord injury (SCI) often results in significant neurologic dysfunction and disability. An annual incidence of 15 to 40 traumatic SCI cases per million population has been reported worldwide, and a conservative estimate for Singapore would be 23 cases per million. With continued improvements in medical care, an increasing prevalence of SCI patients is expected, with corresponding need for comprehensive rehabilitation services led by specialist rehabilitation physicians. METHODS: A literature search, review, and summary of findings of recent studies relating to factors associated with recovery, as well as interventions for rehabilitation and promotion of healing of the injured spinal cord was performed. CONCLUSIONS: Many SCI patients show improvements in motoric and neurologic level, but those with complete injuries have poor chance of improving American Spinal Injury Association (ASIA) scores. SCI of violent aetiology tends to be more neurologic complete, and those without sacral sparing less likely to improve. Older patients generally do well in activities of daily living. Women have better motor score improvement, although men have better Functional Independence Measure (FIM) scores generally. Electrodiagnostic tests such as somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) can help with prognostication, as can imaging techniques such as magnetic resonance imaging (MRI). Immediate surgery for spinal decompression may improve recovery, but whether routine surgery after SCI improves function remains unclear, as does the timing. Methylprednisolone and similar agents appear to help limit secondary injury processes. Rehabilitation interventions such as functional electrical stimulation (FES) and body-weight supported treadmill ambulation training may be effective, as may neural-controlled prostheses and devices. Substances that promote repair and regeneration of the injured spinal cord such as GM-1, 4-AP, BDNG, GDNF, Nogo and MAG-inhibitors, have been studied. Transplanted tissues and cells, such as blood macrophages, bone marrow transplant with GM-CSF, olfactory ensheathing cells, fetal tissues, stem or progenitor cells, have been reported to produce neurological improvements. PMID- 17285187 TI - Emerging therapies in stroke rehabilitation. AB - Traditionally, practitioners of stroke rehabilitation are taught that benefits of rehabilitation are achieved primarily through training patients in new techniques to compensate for impairments, and that neurological recovery is predominantly spontaneous in nature. Recent animal and human experiments have, however, indicated that the adult brain is capable of reorganisation and the term plasticity has been coined to describe this ability. Furthermore, it has been shown that cerebral reorganisation is use-dependent and can be manipulated via appropriate stimuli. This has resulted in a paradigm shift in the way stroke survivors should be rehabilitated and also given rise to several novel rehabilitation techniques. PMID- 17285188 TI - Rehabilitation for traumatic brain injury in children and adolescents. AB - Children and adolescents who have sustained a traumatic brain injury (TBI) may be left with multiple deficits and impairments that can impact adversely their abilities to return to premorbid functioning in the home, school and community. Early rehabilitation has been shown to improve functional outcome; the rehabilitation programme itself has to be based on real-world demands and experiences. Rehabilitation has to be continued beyond the post-acute stage in order to promote neuronal re-organisation, monitor the child's development as well as identify and manage new issues that may appear with growth, development and maturation. The availability of relevant research data and findings for children is much less than those for adults. It is not always appropriate to apply data for adults to the younger persons due to important differences in the 2 groups and these are discussed in more detail in the article. Multiple factors have been found to affect recovery and functional outcome. Apart from age and developmental stage at injury, other variables can be grouped as injury-related, patient-related and treatment-related factors. The goals and components of the rehabilitation process are examined for the various stages of recovery and the last section of the article describes the paediatric rehabilitation scene in Singapore. PMID- 17285189 TI - Characteristics of medical school graduates who underwent problem-based learning. AB - INTRODUCTION: In this study, we compared the choice of medical specialty and subspecialty interest among problem-based-learning (PBL) graduates and non-PBL graduates. MATERIALS AND METHODS: Questionnaires were mailed to a total of 1398 female doctors who graduated from Tokyo Women's Medical University (TWMU) between 1989 and 2003. The response rate was over 30%, giving 248 respondents who had undergone a PBL curriculum (PBL+) and 220 subjects who had not (PBL-). Current specialty of the graduates were compared between the PBL+ and PBL-, and also compared with the general Japanese female doctors (Control 1 and 2) of similar age groups. Respondents were analysed in terms of their interests in subspecialty medical care or general medical practise, which includes comprehensive medical care, primary care and basic medicine. Internal medicine doctors working in the university hospitals were compared with those working outside the university hospitals. Internal medicine doctors were also compared with specialists in ophthalmology, otolaryngology, dermatology and psychiatry. Subjects were compared by odds ratio (OR) to examine group difference in the field of interest. OR >2.0 was considered statistically significant. RESULTS: Most doctors in all groups chose internal medicine. More PBL+ internal medicine doctors showed interests in comprehensive medical care and primary care; more PBL+ internal medicine doctors working outside university hospitals showed interest in comprehensive medical care and primary care when compared with those who were working in the university hospitals. The PBL- graduates did not show such a characteristic. CONCLUSIONS: More PBL+ graduates who chose internal medicine showed interest in holistic medical practices such as primary care and community medicine and more PBL+ specialists showed sustained interest in their respective fields. PMID- 17285190 TI - Emphysematous gastritis: a case report and a review of literature. AB - INTRODUCTION: Gas is rarely found within the viscera outside the lumen of the gastrointestinal tract. Emphysematous gastritis is a rare form of infection of the stomach wall by gas producing organisms. CLINICAL PICTURE: A 45-year-old Chinese lady underwent hepatectomy for hepatocellular carcinoma. Postoperatively, she turned septic and encephalopathic with worsening liver function. Computed tomography scan revealed a thickened, oedematous stomach wall with air pockets within. TREATMENT: The patient was started on a course of broad spectrum antibiotics. OUTCOME: She responded and was discharged well. CONCLUSION: Emphysematous gastritis is a rare condition with high mortality. There is however, still no preferable approach of treatment despite therapeutic advances. PMID- 17285191 TI - Successful rehabilitation with cochlear implant in post-irradiation induced hearing loss in nasopharyngeal carcinoma patient. AB - INTRODUCTION: We report a case of successful rehabilitation of hearing with a cochlear implant in a patient with nasopharyngeal carcinoma who developed post irradiation hearing loss following treatment. CLINICAL PICTURE: A 55-year-old Chinese lady suffered from radiation-induced sensorineural hearing loss due to treatment for nasopharyngeal carcinoma. Audiological tests and imaging studies showed an intact retrocochlear pathway. TREATMENT: Cochlear implantation. OUTCOME: Cochlear implant was done with successful rehabilitation of hearing until the time of this report. CONCLUSIONS: If functionally active auditory fibres survive with no recurrent tumour, successful rehabilitation of post irradiation induced sensorineural hearing loss is possible with a cochlear implant in a patient with nasopharyngeal carcinoma. PMID- 17285192 TI - Sudden deafness due to intralabyrinthine haemorrhage: a possible rare late complication of head and neck irradiation. AB - INTRODUCTION: Radiation injury resulting in sudden, late onset sensorineural hearing loss is a recognised complication in patients who have received head and neck irradiation. We describe the magnetic resonance imaging (MRI) of the internal acoustic canal (IAC) of 3 such patients and postulate a cause for these findings. CLINICAL PICTURE: A total of 63 patients were referred for MRI IAC for sudden-onset sensorineural hearing loss. Of these patients, only 5 patients had abnormal MRI finding in the affected ear and the remaining patients had normal studies. Two patients had acoustic neuromas. Three patients demonstrated high T1 weighted signal in the labyrinths of the affected ears and had past histories of head and neck irradiation. The MRI findings and medical records of these 3 patients were reviewed and described in this case series. OUTCOME: High labyrinthine signal on unenhanced T1-weighted images in the symptomatic ear of these patients was observed, suggesting the possibility of haemorrhage. In the patient who had a history of brain tumour, susceptibility artifacts were also seen in the right hemipons on the gradient-echo images, indicating the presence of paramagnetic substances from previous therapy. CONCLUSION: We postulate that labyrinthine haemorrhage is a rare, late complication of head and neck irradiation, resulting in sudden sensorineural hearing loss. PMID- 17285193 TI - Symphysis pubis diastasis after normal vaginal birth: a case report. PMID- 17285194 TI - Disability and leprosy: the way forward. PMID- 17285195 TI - Update on liver transplantation: indications, organ allocation, and long-term care. AB - Liver transplantation (LT) is definitive treatment for patients with acute liver failure and end- stage liver disease and in a subset of primary hepatic malignancies. For patients who successfully undergo LT, the probability of long term graft and recipient survival is generally excellent, with a high likelihood of return to a relatively normal lifestyle. This article will review current indications, contraindications and postoperative care in LT. With the number of potential recipients far exceeding the number of deceased donor organs, new strategies are being explored to increase access to LT, including: splitting cadaveric donor livers, the use of living donors, and the adoption of the Model for End-Stage Liver Disease (MELD) scoring system, which is based on a mathematical formula to stratify patients in greatest need of transplantation. The allocation of deceased donor organs will, however, remain a contentious issue unless the donor pool is greatly expanded. PMID- 17285196 TI - Translational research in inflammatory bowel disease. AB - The idiopathic inflammatory bowel diseases (IBDs), broadly classified as either Crohn's disease (CD) or ulcerative colitis (UC), are caused by a dysregulated mucosal immune response to a luminal antigen, possibly a bacterium, in a genetically predisposed host. A rapid expansion of knowledge in recent years has greatly increased our understanding of the pathophysiology of these disorders. For example, the relatively recent discovery of the NOD2 gene, a protein involved in bacterial sensing, has provided further evidence of the complex interplay between hosts and microbes in Crohn's disease. Significant recent advances have also occurred with the discovery of the role of Toll-like receptors and dendritic cells in the development of gut inflammation, and the role of proinflammatory cytokines in the development and potentiation of gut inflammation. This article presents an update on these key developments and emphasizes the translational aspects of research that are directly related to patient care. PMID- 17285197 TI - Acute ischemia of the lower extremity in the pediatric population: a protocol for management. AB - Each year, a large number of infants and children undergo vascular catheterization via access in a lower extremity. The femoral system is relatively easy to cannulate, and this approach avoids use of more central access approaches that may present more serious complications. Infrequently, however, pediatric patients develop acute ischemia of the ipsilateral lower extremity. Several surgical and nonsurgical treatment options exist for the management of such problems. However, no adequate protocol exists for the management of acute lower extremity ischemia in the pediatric population. The authors present several cases of distal lower extremity ischemia as a result of femoral artery catheterization and offer a protocol for management of similar cases. PMID- 17285198 TI - An intraluminal leiomyoma of the small intestine causing invagination and obstruction: a case report. AB - Leiomyomas are mostly of benign character and are rarely seen in the gastrointestinal (GI) system. They represent one subgroup of a group of tumors known as gastrointestinal stromal tumors (GIST). Although rarely seen, they are symptomatic tumors, and they comprise 20-30 percent of all benign GI tumors. Diagnosis is difficult because of their rarity and the absence of specific symptoms. This is a case report of intestinal leiomyoma in a patient who was suffering with GI obstruction for more than 5 months. The tumor was discovered only after the appearance of intestinal obstruction. The patient underwent laparotomy for ileus of unknown etiology. Leiomyoma was diagnosed by pathologic analysis. PMID- 17285199 TI - Superior vena cava syndrome (SVC syndrome): a rare cause of conjunctival suffusion. AB - Obstruction of blood flow in the superior vena cava results in the signs and symptoms of superior vena cava (SVC) syndrome. Venous collaterals form, to establish alternative pathways for return of venous blood to the right atrium. The rapidity of onset of symptoms and signs from SVC obstruction is directly related to the rate at which obstruction occurs and how effective the formed collaterals are. Lung cancer and lymphoma account for more than 90% of cases of SVC syndrome. Recognition of signs and symptoms allows us to make an early diagnosis. Facial swelling, distended veins over the neck, upper extremity swelling, and dyspnea are common findings. Proptosis, periorbital swelling (including eyelid), conjunctival suffusion and elevated intraocular pressure are documented ophthalmic findings in SVC syndrome. We present a rare case of conjunctival suffusion in a 72-year-old male diagnosed with superior vena cava syndrome secondary to lung cancer. PMID- 17285200 TI - Effects of N-acetylcysteine on methotrexate-induced small intestinal damage in rats. AB - Methotrexate (MTX) is known to cause damage to the small intestine, leading to its dysfunction. The aim of the present study was to examine whether the administration of N-acetylcysteine (NAC) provides protection against the MTX induced damage to small intestinal epithelium in rats. A single dose of MTX (20 mg/kg, intraperitoneal) was followed by intraperitoneal saline or NAC administration (150 mg/kg, MTX+NAC group) for the next 5 days. Afterward, the rats were sacrificed and small intestinal segments were fixed for light microscopic examinations. Glutathione and malondialdehyde levels, myeloperoxidase, superoxide dismutase and catalase activities were measured in the other intestinal segments. MTX caused an increase in the levels of glutathione and malondialdehyde and in the activities of myeloperoxidase, superoxide dismutase and catalase. These changes were significantly reversed in MTX+NAC-treated rats. Light microscopy in the MTX group revealed mucosal damage, which decreased with NAC treatment. Our results confirmed that administration of NAC decreased the MTX-induced damage to the small intestine. This protective effect of NAC may have clinical applications in chemotherapy. PMID- 17285201 TI - An unusual post-traumatic case of extrahepatic bile duct compression. AB - Jaundice and cholestatic disease by external bile duct compression may be caused by several conditions, including pancreatic masses, portal cavernoma, Ormond's disease, metastases from gallbladder cancer, neurinomas, and hydronephrotic kidney. We report a case of bile duct compression in a 56-year-old man with a known small (28 mm) right renal cyst and crossed, fused renal ectopia. The patient had a history of recent abdominal trauma due to a motorcycle accident and recurrent septic-type fever and jaundice. He also reported a weight loss of 5 kg in the last two months. Abdominal ultrasonography showed intra- and extra-hepatic bile duct dilatation, and computed tomography scan showed hydronephrosis, dilatation of intra- and extra-hepatic biliary tract, and a right renal complex cyst of more than 9 cm. One can hypothesize a relationship between the abdominal trauma and the increase in size of the renal cyst, which, moreover, had changed its original shape. The patient underwent cefuroxime and metronidazole therapy, with complete recovery from the cholangitis within one week. The treatment of choice would have been surgical excision or, alternatively, an image-guided percutaneous aspiration of the cyst, in order to avoid further episodes of cholangitis. Unfortunately, the patient refused either surgical or more conservative treatment and was lost to follow-up. PMID- 17285202 TI - Erythrocytosis in a patient on hemodialysis for thirteen years. AB - Most hemodialysis patients exhibit renal anemia mainly due to erythropoietin deficiency as a result of impaired erythropoetin production in the kidney. However, erythrocytosis in patients with renal failure requiring hemodialysis is extremely rare. We report the development of erythrocytosis in a patient with a polycystic kidney disease on hemodialysis for 13 years. She had erythrocytosis with increased serum erythropoietin levels despite severe secondary hyperparathyroidism, which is known to depress erythrocytosis. Since neither renal disease (renal cell carcinoma) nor extrarenal diseases (hypoxia, hepatoma, cerebellar diseases) linked with erythropoietin production could be proven, this case might be one with inappropriate idiopathic erythropoietin production after 13 years of hemodialysis, the longest duration of dialysis in the literature before erythrocytosis was observed. PMID- 17285203 TI - Soil-transmitted helminths and Plasmodium falciparum malaria: epidemiology, clinical manifestations, and the role of nitric oxide in malaria and geohelminth co-infection. Do worms have a protective role in P. falciparum infection? AB - Malaria and intestinal helminths are sources of significant morbidity worldwide. Given the nature of shared endemicity, these diseases often co-exist in the same populations. Therefore, much attention is now being given to the interaction between helminths and Plasmodium in the situation of co-infection. Existing evidence is consistent with the hypothesis that helminths are associated with continued and possibly increased incidence of malaria infection. However, data from some recent clinical fieldwork suggest protection from cerebral malaria in the setting of helminth co-infection. Nitric oxide, coupled with the immunoglobulin E (IgE) receptor, CD23, appears to be a crucial factor in preventing the development of cerebral malaria, thus improving chances for the survival of both host and parasite. In this work, we review literature on the subject of helminth and malaria co-infection, and offer a theoretical explanation of the helminth modulation of clinical malaria. In doing so, we advocate further research on this subject and also the need for a dual approach in global disease control intervention, which simultaneously targets both malaria and geohelminth infection. PMID- 17285204 TI - A randomized, placebo-controlled trial of a single dose of tropisetron for the prevention of vomiting after strabismus surgery in children. AB - PURPOSE: This study evaluates the effect of different doses of tropisetron to prevent postoperative vomiting, which frequently occurs in children following strabismus surgery. METHODS: One hundred twenty-five American Society of Anesthesiologists' classification (ASA) I-II group patients 2-12 years of age were randomized to this prospective, single-blind, placebo-controlled clinical study. Patients were placed in groups of 5 and did not receive any premedication. The first group received placebo, and the 2nd, 3rd, 4th, and 5th groups received 0.5 mg/m(2), 1 mg/m(2), 1.5 mg/m(2), and 2 mg/m(2) of tropisetron, respectively, following anesthesia induction. The same anesthetic technique and analgesia were used for all groups. The patients were examined for the presence of vomiting and for any complaints and side effects at 2, 6, and 24 hours after surgery. RESULTS: The incidence of postoperative vomiting (POV) was statistically more significant in the placebo group at 2, 6 and 24 hours, when compared to the study groups (p< 0.001), but there was no significant difference among tropisetron groups at 6-24 hours (p>0.05). There was no significant difference in terms of the incidence of POV among the study groups (16%, 16%, 24%, 20% respectively) at all periods (p>0.05). The number of patients with POV score of 3 was 10 in the placebo group, while it was 1, 2, 0 and 1 in the 2nd, 3rd, 4th, and 5th groups, respectively (p<0.01). CONCLUSIONS: Tropisetron (0.5, 1.0, 1.5 and 2.0 mg/m(2)) decreased the incidence and severity of POV following strabismus surgery in children. All of the doses seemed to be equally effective. There was no difference in POV control between placebo and any of the doses of the tropisetron after six hours. So we suggest that 0.5 mg/m(2) single-dose tropisetron is enough for preventing POV following strabismus surgery in children. PMID- 17285205 TI - Tuberculous peritonitis and tuberculous endometritis diagnosed in the same patient by high clinical suspicion and a minimally invasive approach. AB - Tuberculous peritonitis and tuberculous endometritis are extremely rare entities in the Western world. In this article, we discuss a rare case of a 40-year-old Nigerian female presenting with abdominal pain, distension and secondary amenorrhea, and show that a high clinical suspicion combined with minimally invasive procedures can help physicians make the diagnosis, avoid extensive surgery, and rapidly initiate appropriate therapy. PMID- 17285206 TI - Ileosalpingeal fistula: an unusual complication of Crohn's disease. AB - Enterosalpingeal fistula is a rare complication of Crohn's disease that is rarely diagnosed pre-operatively. We describe two cases of enterosalpingeal fistula. Both cases were diagnosed during exploration and required en bloc resection of the small bowel and fallopian tube. Literature review yielded only one specific case report of ileosalpingeal fistula and two other cases described in a larger series. Management of ileosalpingeal fistula should include resection of the diseased bowel as well as removal of the affected fallopian tube. Crohn's disease has an extremely wide spectrum of clinical manifestations. The hallmark of Crohn's disease is bowel inflammation with fistula or stricture formation. Organs commonly involved in fistula formation include the skin, small bowel, colon, and bladder. Rare fistula sites include the duodenum, stomach and gynecological structures such as the ovaries, fallopian tubes and vagina. We present two cases of Crohn's disease of the terminal ileum fistulizing to the fallopian tube. There is only one specific report of an ileosalpingeal fistula, although another author has described two additional cases in a large series of Crohn's fistulas. PMID- 17285207 TI - Multimodal characterization of a large right atrial mass after surgical repair of an atrial septal defect. AB - A 43-year-old woman with exertional dyspnea and a history of surgically repaired atrial septal defect was referred for a transthoracic echocardiogram, which demonstrated a large, mobile mass in her right atrium. The mass was further characterized with contrast transesophageal echocardiography (TEE) and delayed enhancement MRI, which together suggested a thrombus, attached to the eustachian valve and prolapsing through the tricuspid valve. The mass was resected and the diagnosis confirmed on histopathologic examination. This case illustrates the utility of a multimodal approach in characterizing cardiac masses. PMID- 17285208 TI - Intracranial hemorrhage associated with methanol intoxication. AB - Methanol is a common component of gasoline, antifreeze, washer fluid, perfume, household cleaners and various other industrial products. Acute methanol poisoning produces severe metabolic acidosis, serious neurologic sequelae and rarely imaging findings. In this paper, we describe a 35-year-old man with methanol intoxication who was in a comatose stage. Computed tomography (CT) showed widespread brain edema and hemorrhages localized in the supratentorial region of the temporal lobe, nearly 3 x 1 cm in a crescent shape, in the white matter surrounding the capsula externa and extending to the periventricular white matter and occipital lobes. Temporal lobe hemorrhage in our patient might also have been due to the effect of heparinization during hemodialysis, metabolic and lactic acidosis, or formate. PMID- 17285209 TI - Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the stomach and small intestine: a case report. AB - This is a case report on a 45-year old African-American female with newly diagnosed hypertension, who was started on a combination pill of amlodipine/benazapril 10/5 mg. The very next day, she presented at the emergency room (ER) with abdominal pain, nausea and vomiting. Physical exam, complete metabolic panel, and hemogram were in the normal range. She was discharged from the ER after a few hours of treatment with fluid and analgesics. However, she returned to the ER the next day with the same complaints. This time the physical exam was significant for a distended abdomen with dullness to percussion. CT scan of the abdomen revealed markedly thickened antrum of the stomach, duodenum and jejunum, along with fluid in the abdominal and pelvic cavity. Angiotensin converting enzyme inhibitor (ACEI)-induced angioedema was suspected, and anti hypertensive medications were discontinued. Her symptoms improved within the next 24 hours, and repeat CT after 72 hours revealed marked improvement in stomach and small bowel thickening and resolution of ascites. The recognition of angiotensin converting enzyme (ACE) and angiotensin receptor blocker (ARB) intestinal angioedema constitutes a challenge to primary care physicians, internists, emergency room personal and surgeons. PMID- 17285210 TI - Guillain-Barre syndrome complicated by myocarditis. AB - Guillain-Barre syndrome (GBS) is an autoimmune disease affecting the peripheral nerves, and is frequently associated with triggering events several weeks prior to the onset of symptoms. We report the case of a 68-year-old female who was diagnosed with GBS and subsequently developed myocarditis. She was treated with inotropic support and intravenous immunoglobulin (IVIG), and her condition improved. This presentation of GBS complicated by myocarditis is very rare. We examined the literature regarding this association. PMID- 17285211 TI - Painless, acute aortic dissection presenting as an acute stroke. AB - Acute aortic dissection is an uncommon disease; however, it has a high mortality rate. Classically, aortic dissection presents with sudden and severe pain in the chest, back, or abdomen. Patients often describe tearing or ripping pain. There are a few reports of atypical findings or no pain in the literature. We report a case of painless, acute aortic dissection presenting as acute stroke. PMID- 17285212 TI - Gallstone ileus: a review. AB - This article aims to review gallstone ileus in the literature addressing the pathophysiology, clinical presentation, radiological findings and treatment options of the condition. A literature search was done on gallstone ileus, for the period 1966-2005. Gallstone ileus is a disease of the elderly, causing up to one fourth of non-strangulation intestinal obstructions in patients older than 65 years of age. It is often missed or diagnosed late. The presentation is that of intestinal obstruction preceded by biliary complaints. Radiological features on plain X-rays include features of intestinal obstruction and pneumobilia, and an aberrant gallstone. Treatment depends on the site of the impacted stone, but surgery is needed in many cases. Gallstone ileus is a rare complication of a common condition. Because it primarily affects the elderly, mortality and morbidity are high, although they have improved over the years. Early diagnosis and treatment improve the outcome. PMID- 17285213 TI - Massive hemoperitoneum from transhepatic perforation of the gallbladder. AB - Perforation of the gallbladder occurs in 1.6%-2.8% of cases of gallbladder disease. Transhepatic rupture of the gall bladder is rare, with fewer than 20 cases reported in literature. We report a case of transhepatic rupture of the gall bladder with massive hemoperitoneum, which required emergency laparotomy and control of hemorrhage. PMID- 17285214 TI - Forensic child abuse evaluation: a review. AB - This review discusses the forensic medical and psychological assessments of children and adolescents suspected of being victims of sexual or physical abuse/neglect. Evaluation of the whole child and the need to minimize trauma during the investigative and assessment processes are stressed. The forensic medical examination is reviewed, including the specifics of the pediatric anogenital examination. The key components of the forensic medical examination in sexual assault cases are also reviewed, with particular attention to maintaining the integrity of the process. Special emphasis is placed on the forensic interview in child sexual abuse cases, the best evidence available and areas in need of further research. PMID- 17285215 TI - Pediatric organ transplant patients and long-term care: a review. AB - We review the role of the academic generalist in the care of the child or adolescent who has undergone an organ transplant. This care is seen within the context of the "medical home" and the special considerations for pediatric patients. These special considerations include growth and development, psychosocial adjustment, cardiac and renal complications, endocrine problems, medication management and regimen adherence, infectious complications, vaccination, post-transplant malignancies, post-transplant lymphoproliferative disorders, acute post-transplant complications, recurrence, contraception and pregnancy for adolescents, and transition to adulthood. Research needs in this complex area are highlighted. PMID- 17285216 TI - Training needs of pediatricians facing the environmental health and bioterrorism consequences of September 11th. AB - OBJECTIVE: The September 11, 2001, terrorist attacks have been called "the worst environmental disaster in the history of New York City." As a result of the extensive nature of the destruction, our objective as pediatricians was to determine the experience and training needs of tri-state child health professionals in responding to the environmental health and bioterrorism-related demands placed on their practices. METHODOLOGY: American Academy of Pediatrics members in New York, Connecticut, and New Jersey were sent either a web-based or a paper survey requesting demographic data and data about post-9/11 practice experience and perceived knowledge with regard to environmental health and bioterrorism. RESULTS: Of the 1,396 respondents, 21% believed their practices to have been "very [much] affected" by the attacks. Eleven percent were often/very often asked by parents about air quality, 12.6% about environmental toxins, 4.3% about antibiotics for anthrax, and 4.2% about potassium iodide for nuclear events. Fifty-seven percent and 49.1% of respondents had patients present with environmental health and bioterrorism-related complaints, respectively. Most (86%) reported that their medical training had not sufficiently prepared them to meet these demands. Few considered themselves to be knowledgeable about bioterrorism (23.9%), local environmental issues (14%), air quality (11.4%), or environmental toxins (12.6%). Gender, race, practice setting, practice location, specialty, and level of training were associated with demands on practice. Location, age, years in practice, and gender were associated with level of preparedness. CONCLUSIONS: Our results indicate that nearly all child health professionals would benefit from post-disaster education, especially trainees. A role for the pediatric associations in the dissemination of this crucial information is implied. PMID- 17285217 TI - Resident as teacher: educating the educators. AB - BACKGROUND: Medical students receive their clinical training from various sources: from residents during informal teaching sessions and from attending physicians during more formalized rounds. As a result of the increasing pressures of clinical medicine, efforts need to be focused on the identification and training of the next generation of clinical educators. DESCRIPTION: We have created a pilot medical education elective for residents which pairs training in teaching skills with formal teaching opportunities during protected blocks of elective time, an opportunity which is rare in most residency programs and may provide for more effective teaching skill acquisition. RESULTS: Feedback from the participants demonstrates widespread acceptance of the pilot program. CONCLUSIONS: We believe this new model would provide motivated residents with the skills and the protected time to teach, and help create a future generation of attendings better able to teach. PMID- 17285218 TI - Sepsis-induced disseminated intravascular coagulation: a rare complication of sacrococcygeal pilonidal sinus disease. PMID- 17285219 TI - [Congenital urogenital malformations associated with nephroblastomas. Long-term results of a study in Erlangen]. AB - BACKGROUND: Wilms' tumors are highly malignant tumors of the kidneys and are among the most frequent solid tumors of childhood, which are diagnosed for the most part before the 5th year. Various congenital anomalies are associated with a genetic predisposition and thus an increased risk of developing a Wilms' tumor. PATIENTS AND METHODS: As part of a retrospective analysis, the records from 1965 to 2003 of 66 patients with histologically confirmed Wilms' tumor were reviewed. The aim of this study was to determine the incidence and type of different urogenital malformations as well as the genetic mutations and overall survival in this patient group. RESULTS: The patient cohort comprised 66 patients with histologically confirmed Wilms' tumor: 35 male patients (53%) and 31 female patients (47%). The overall survival after 10 years was 89.4%. All patients underwent radical nephrectomy: transperitoneal approach in 63 and lumbar approach in 3 patients. Eleven (16.7%) patients had diverse urogenital anomalies. A cytogenetic investigation was performed in 38 patients that revealed no pathological findings. The results of molecular genetic testing of tumor specimens were available for seven patients: a genetic mutation was detected in one case (heterozygous mutation R394 in exon 9 of the WT1 gene) which had already been described in the literature in conjunction with Denys-Drash syndrome. Hemihypertrophy with Beckwith-Wiedemann syndrome was present in two (3%) patients. CONCLUSION: In patients with urogenital malformations and Wilms' tumor, it would be important to carry out further molecular genetic testing to identify possible WT1 gene mutations. Close interdisciplinary cooperation between urologists, specialists in human genetics, and pediatricians is imperative. PMID- 17285220 TI - [Prostatitis syndrome]. AB - Prostatitis syndrome is a multifactorial disease with a largely unknown etiology. Quite different therapeutic options are therefore recommended. According to the new NIH classification, pathogens can be cultured only in acute and chronic bacterial prostatitis. A long-term antimicrobial therapy, mainly with fluoroquinolones, is then recommended. Most patients suffer from chronic pelvic pain syndrome (CP/CPPS) which can be subdivided into inflammatory and non inflammatory types. Whether the inflammatory CP/CPPS is an infectious disease remains uncertain. The effect of an antibiotic therapy therefore remains debatable. In case of proven or suspected functional infravesical obstruction, treatment with a-receptor blockers is recommended. Accompanying symptomatic therapy is also recommended. It is important, however, to keep the patient fully informed about the diagnostic and therapeutic limitations. PMID- 17285221 TI - Household work disability of Arab housewives with rheumatoid arthritis. AB - There have been few studies on the impact of rheumatoid arthritis (RA) on household work, and none has been done in a setting where female unemployment is normative. The typical Israeli Arab woman is nearly always unemployed, poorly educated, has low financial resources, and is fully responsible for maintenance of the household work. In this study, we attempted to determine whether social economic factors or medical evaluation best predicts household work disability. Arab housewives with RA that are followed up regularly with disease duration >6 months were recruited consecutively from three outpatient clinics in northern Israel. These patients had to answer a questionnaire regarding demographic and social data, performance of typical household activities, patient-family relationship, and disease parameters. Information from the medical charts was also obtained on all the patients regarding erythrocyte sedimentation rate (ESR), C-reactive protein, tender joint count (28 joints), and swollen joint count (28 joints), all from the last visit. Information was obtained also on bone erosions, rheumatoid factor positivity, and disease duration. Those who could not perform at least one household activity were defined as being disabled and compared to those who have no such disability. Forty-eight patients completed the study, and 33 (68.8%) patients were disabled (unable to do at least one household activity). The disabilities in the 33 patients included total inability to clean the house in 30 (91%), inability to wash the floor in 28 (84.8%), inability to take care of the children or husband in 18 (54.5%), inability to wash the dishes in 15 (45.5%), and inability to cook in 10 (30.3%). There were three variables that significantly added to a logistic regression model predicting disability; husband's salary, the number of kids in the family, and the ESR. This model was excellent with the area under the receiver-operator curve (ROC) of 93.1%. Substituting years of symptoms for ESR also resulted in an excellent model with the area under the ROC of 90.8%. None of the other variables including findings on physical examination significantly added to the model. We conclude that socio economic factors are highly predictive of homemaking disability in Arab women with RA and more predictive than the clinical examination. Further studies in other cultures are needed to substantiate our results. PMID- 17285222 TI - Sexual problems in male ankylosing spondylitis patients: relationship with functionality, disease activity, quality of life, and emotional status. AB - This study has focused on sexual problems of male ankylosing spondylitis (AS) patients. Initially, patients' perceptions about the effects of disease on sexual intercourse were assessed. Secondly, we investigated the factors that relate to the disease and affect sexual intercourse negatively. Thirdly, we compared data from the patients whose sexual intercourse were affected negatively with of those whose sexual intercourse were unaffected. This is a cross-sectional and double centered study. A total of 53 married or sexually active male patients, who were certainly diagnosed with AS according to modified New York criteria, were assessed. Twenty seven patients (50.94%) expressed that their sexual life was affected negatively by the AS in general (affected patients), and 26 patients (49.06%) expressed no negative effect (unaffected patients). Both affected and unaffected patients were compared with each other with regard to educational level, joint involvement, functionality, disease activity, quality of life, and depression status. Mean BASFI, BASDAI scores were worse in the affected group, and the difference was statistically significant (p = 0.012, p = 0.039, respectively). There were statistically significant differences between the groups with regard to lumbar column and hip involvement (p = 0.035, p = 0.021; respectively). The physical functioning, role limitations due to physical problems, vitality/energy/fatigue, general mental health, and general health perception subscale scores of SF-36 were worse in the affected group, and the differences were statistically significant (p = 0.027, p = 0.023, p = 0,013, p = 0.005, p = 0.045, respectively). Affected patients' Beck Depression Inventory scores were worse than those of unaffected patients, and the difference between the groups was statistically significant (p = 0.039). Sexual problems are common in AS patients and might usually be associated with joint involvement, decreased functionality, increased disease activity, decreased health quality, and depression. Therefore, while examining AS patients and managing their treatments, special attention must be given to all domains of life instead of only physical problems. PMID- 17285223 TI - The development of systemic sclerosis classification criteria. AB - Systemic sclerosis (SSc) is a rare connective tissue disorder whose aetiology remains obscure, although environmental and genetic influences are likely to play a role. Disease registries have contributed to enhancing our understanding of this debilitating illness, but without sensitive, specific, and extensively validated classification criteria, accurate comparison between registries and the identification of patients suitable for clinical trials can be problematic. The American College of Rheumatology (ACR) criteria, published in 1980, have become outdated as our understanding of disease specific autoantibodies and nailfold capillaroscopy has improved. In addition, the sensitivity of the ACR criteria is low with respect to limited SSc. Although subsequent classification systems have been proposed, none has gained universal approval. The two- versus three-subset disease model remains a point of debate. Newly derived criteria are likely to draw upon the older classification systems as well as incorporating up-to-date diagnostic techniques and biomarkers. Validation will be critical before their use becomes widespread. PMID- 17285224 TI - Low serum level of COMP, a cartilage turnover marker, predicts rapid and high ACR70 response to adalimumab therapy in rheumatoid arthritis. AB - The aim of this study was to evaluate serum biomarkers, used in clinical routine, to predict the American College of Rheumatology (ACR) response to long-term anti TNF alpha treatment (adalimumab). Sera from 29 consecutive rheumatoid arthritis patients were analysed for anti-cyclic citrullinated peptide (anti-CCP), cartilage oligomeric matrix protein (COMP) and IgM and IgA RFs (class-specific rheumatoid factors) at the start of treatment with adalimumab and after 3, 6 and 12 months. The response to the therapy was evaluated by ACR 20, 50, 70 and by DAS 28 scores. The mean serum COMP level of the population did not change after treatment. However, patients with low serum COMP levels (<10 U/l) at baseline showed a significant (p<0.02) higher ACR70 response (>50%) within 3 months, and also at 6 months, than patients with higher COMP values (ACR70<20%). This was also reflected by significantly higher decrease in DAS score at 3 (p<0.02) and 6 months (p<0.01) treatments. The IgM RF titre decreased significantly (p=0.02) after the therapy, but the percentage of serum positivity for anti-CCP and IgA/IgM RF did not change. No significant correlation was shown between serum COMP levels and C-reactive protein/erythrocyte sedimentation rate during the follow-up. Neither were any correlations shown between ACR/DAS 28 scores and anti CCP, Ig M/IgA RFs. Our data indicate that low (<10 U/l) serum COMP before starting anti-TNF alpha treatment predicts a rapid (within 3 months) and high ACR70 response compared to RA patients with higher COMP values. This might reflect different mechanisms in the cartilage process in the RA disease at that time of treatment with different therapeutic sensitivity to anti-TNF alpha treatment. PMID- 17285225 TI - Changes in short-term measures of heart rate variability after eight weeks of cardiac rehabilitation. AB - BACKGROUND: In coronary artery disease (CAD) and following myocardial infarction (MI), activity of the autonomic nervous system is altered. Reduced heart rate variability (HRV) is a risk factor for future cardiac event. Studies reporting changes in HRV post-cardiac rehabilitation (CR) are heterogeneous, due possibly to varied data collection and analysis protocols. AIM: To evaluate changes in spectral measures of HRV derived from 5-minute ECG recordings in patients completing an 8 weeks CR programme. METHODS: Thirty-eight patients (21 males, 17 females, aged 65.6 +/- 11.6 years) underwent 5 minutes, supine ECG recordings and standard physiological and psychological assessment pre- and post-CR. A further 23 patients (14 males, 9 females aged 64.9 +/- 9 years) acted as controls. Outcome measures were: low frequency power, (LF, 0.04-0.15 Hz) high frequency power (HF, 0.15-0.40 Hz), LF:HF ratio and mean RR interval. Change was assessed by ANCOVA and paired t-tests. RESULTS: When compared with the CT group, the CR group showed significant increases in: SDNN (Delta +6 ms, CR vs. 0 ms CT), HFln (Delta 0.4 log units CR vs. 0 log units CT), LFln (Delta +0.6 log units CR, vs. +0.1 log units CT) and RR interval (Delta +30 ms, CR vs. -28 ms CT). CONCLUSIONS: This is the first study to show significant increases in raw LF and HF power derived from short-term ECG recordings in CR patients. These measures are risk factors for future cardiac event. As CR is associated with increases in these measures it may be viewed as an effective therapy capable of bringing about favourable alterations in autonomic control. PMID- 17285226 TI - Does modafinil enhance activity of patients with myotonic dystrophy?: a double blind placebo-controlled crossover study. AB - We performed a double-blind placebo-controlled crossover study in 13 patients with myotonic dystrophy to address the question whether modafinil, known to improve hypersomnolence in myotonic dystrophy, may improve levels of activity as well. We used the Epworth Sleepiness Scale as a measure of hypersomnolence and a structured interview of the patient and the partner or housemate as a measure of activity. We additionally used a restricted form of the RAND-36 to relate a possible improvement of activity to perceived general health. We confirmed earlier positive findings of modafinil regarding reduced somnolence (p=0.015), but no significant effects were seen regarding activity levels (p=0.2 for patients' self-reports and 0.5 for partners' reports). PMID- 17285227 TI - Cloning and expression analysis of YY1AP-related protein in the rat brain. AB - YY1AP-related protein (YARP) is a structural homolog of YY1AP, a transcriptional coactivator of the multifunctional transcription factor YY1. We cloned a rat YARP cDNA that encoded a 2256 amino acid protein with 93% homology to the human counterpart. Northern blots revealed significant expression of the YARP gene in the rat brain. In situ hybridization demonstrated its expression in neurons throughout the brain, including pyramidal cells in the cerebral cortex and hippocampus and granule cells in the dentate gyrus. YARP was coexpressed with YY1 in these same neuronal cells. However, there was no evidence of YARP expression in glia. In the developing rat brain, the level of YARP mRNA ( approximately 10 kb) peaked at embryonic day 18 and promptly declined thereafter to reach the steady-state level found in adulthood, by 14 days after birth. These results suggest that YARP functions at a late stage of neurogenesis during perinatal development of the rat brain, as well as in mature neurons. PMID- 17285228 TI - Mechanisms of homocysteine toxicity in humans. AB - Homocysteine, a non-protein amino acid, is an important risk factor for ischemic heart disease and stroke in humans. This review provides an overview of homocysteine influence on endothelium function as well as on protein metabolism with a special respect to posttranslational modification of protein with homocysteine thiolactone. Homocysteine is a pro-thrombotic factor, vasodilation impairing agent, pro-inflammatory factor and endoplasmatic reticulum-stress inducer. Incorporation of Hcy into protein via disulfide or amide linkages (S homocysteinylation or N-homocysteinylation) affects protein structure and function. Protein N-homocysteinylation causes cellular toxicity and elicits autoimmune response, which may contribute to atherogenesis. PMID- 17285229 TI - Atypical papillary glioneuronal tumor. AB - We describe a 34-year-old man who presented with headaches for about 3 months. Magnetic Resonance Imaging (MRI) revealed a large cystic tumor, involving the right frontoparietal lobe region. Pathological study revealed a papillary glioneuronal tumor (PGNT) with mitotic activity and a Ki-67 labeling index of approximately 15%. Five years after radical surgery and radiotherapy, the patient is symptom-free, without tumor recurrence or residual tumor. This case supports the existence of an atypical variant of PGNT, with mitotic activity and high proliferative index, and suggests that in these tumors, histological findings of malignity not necessarily indicate a short-term unfavorable behavior. PMID- 17285230 TI - Prognostic significance of co-overexpression of the EGFR/IGFBP-2/HIF-2A genes in astrocytomas. AB - Overexpression of the EGFR, IGFBP-2 and HIF-2A genes has been observed in high grade astrocytomas and these genes seem to be functionally related to one another. This study aimed to define the profile of their expressions, interactions and correlation with clinical features and prognostic significance in microdissected tumor samples from 84 patients with astrocytomas of different grades and from 6 white matter non-neoplasic brain tissue sample. EGFR, IGFBP-2 and HIF-2A gene expression levels were analyzed by quantitative real-time PCR and differed significantly between grades I-IV astrocytic tumors (P < 0.0001, P < 0.0001 and P: 0.0013, respectively) when analyzed by the Kruskal-Wallis test. Grade I astrocytomas presented gene expression levels similar to those encountered in samples of microdissected white matter of non-neoplastic brain tissue Overexpression of the EGFR, IGFBP-2 and HIF-2A genes was significantly associated with lower 2-year survival (P: 0.009, P: 0.0002 and P: 0.008, respectively). Co-overexpression of these genes was strongly associated with high grade gliomas and lower survival in univariate (P < 0.0001) and multivariate (P: 0.009) analysis, suggesting that the co-expression of the EGFR/IGFBP-2/HIF-2A pathway genes may have a more important clinical and biological impact than the expression of each individual gene alone. These data support the existence of a common pathway involving these genes that could contribute to the design of new target treatments. PMID- 17285231 TI - Combined abdominal and perineal approach for delayed restoration of bowel continuity after low anterior resection in females. AB - Restoration of bowel continuity after Hartmann's operation is the surgeon's goal and the patient's hope. This operation is technically demanding with reportedly high morbidity and mortality. A short distal rectal stump often makes the operation more difficult. In this article, we describe a combined abdominal and perineal approach, which can possibly make delayed restoration of bowel continuity after low anterior rectal resection an easier procedure. PMID- 17285232 TI - Diabetes mellitus and anal sphincter pressures: an experimental model in rats. AB - PURPOSE: Symptoms of the gastrointestinal tract, frequent in patients with diabetes mellitus, which may be related to an increase in the production of free radicals, include alterations in the function of the sphincter anal musculature. Such alterations are characterized by a decrease of muscular tone associated with different degrees of fecal incontinence. This study was performed to show the alterations in the anal sphincter pressures of diabetic rats and to evaluate the role of nitric oxide and oxidative stress in this situation. METHODS: Male Wistar rats weighing 250 to 400 g were used. The animals were divided in two groups: control and diabetic. Diabetes was induced through intraperitoneal injection of streptozotocin and the anal pressures were gauged by anorectal manometry. Nitric oxide was evaluated through measures of nitrites and nitrates, and oxidative stress through the technique of chemoluminescence. RESULTS: There was a significant decrease in the sphincter anal pressure of diabetic animals 60 days after induction (P < 0.05). This pressure returned to basal values after administration of a nitric oxide synthase antagonist. The levels of nitrites and nitrates as well as of lipoperoxidation were significantly increased in the diabetic compared with the control group (P < 0.05). CONCLUSIONS: In this study, hyperglycemia of diabetes mellitus caused an increase in the oxidative stress. Apparently the elevation of nitric oxide levels was one of the responsible factors for the decrease of anal sphincter pressures. PMID- 17285233 TI - Local therapy for rectal cancer: still controversial? AB - PURPOSE: Many considerations, such as morbidity, sexual and urinary dysfunction, or risk of definitive stoma have led to the increased popularity of local therapy in the therapeutic strategy for rectal cancer. However, its role in curative intent is still controversial with oncologic long-term results lower than those obtained by radical surgery. METHODS: MEDLINE, EMBASE, LILACS, Abstract books, and reference lists from reviews were searched with English language publications to review the current status of evidence for local therapy in rectal cancer, looking especially at the oncologic results and patient selection. We have focused on the new strategies combining neoadjuvant and adjuvant treatment to explain their place in the management of rectal cancer. RESULTS AND CONCLUSIONS: The key to potentially curative local treatment for rectal cancer is patient selection by identifying the best candidates with preoperative tumor staging and clinical and pathologic assessment of favorable features. Low-risk T1 is suitable for local excision alone. Limited data suggest that adjuvant chemoradiotherapy may be helpful in patients with unfavorable T1 and T2 lesions, achieving a local recurrence rate<20 percent. However, the efficacy of salvage surgery after local excision is uncertain. PMID- 17285234 TI - Patient satisfaction and health-related quality of life after treatment for colon cancer. AB - PURPOSE: Health-related quality of life has become an important outcome in cancer treatment. Detailed health-related quality of life measures were taken as part of a trial of follow-up of patients with colon cancer by general practitioners and surgeons. This study was designed as a longitudinal assessment of health-related quality of life after treatment for carcinoma of the colon and patient satisfaction with two different settings of follow-up (general practitioners vs. surgeons). METHODS: A total of 338 patients were recruited into randomized (n = 203) and patient preference (n = 135) follow-up groups. Prospectively assessed physical and mental health-related quality of life measures and patient satisfaction are reported during two years. RESULTS: Elderly and less educated patients prefer follow-up by general practitioners over surgeons. Overall, physical health-related quality of life is reduced early after treatment; however, this returns to normal levels at one year. Mental quality of life, anxiety, and depression are at or above population levels throughout the two-year follow-up period. There were no differences in physical or psychologic health related quality of life measures between general practitioner and surgeon groups at any time during follow-up. Overall, more advanced Dukes stage is associated with a trend to improved mental health-related quality of life. Patients' ability to choose the setting of follow-up has no influence on health-related quality of life compared with random allocation to general practitioner or surgeon. Patients are equally highly satisfied with follow-up by general practitioner or surgeon. CONCLUSIONS: After recovery from treatment for colon cancer, health-related quality of life is similar to the general population. Good health-related quality of life outcomes and high patient satisfaction are as well provided by general practitioners in the community setting as by surgeon review. PMID- 17285235 TI - Current-use pesticides and organochlorine compounds in precipitation and lake sediment from two high-elevation national parks in the Western United States. AB - Current-use pesticides (CUPs) and banned organochlorine compounds (OCCs) were measured in precipitation (snowpack and rain) and lake sediments from two national parks in the Western United States to determine their occurrence and distribution in high-elevation environments. CUPs frequently detected in snow were endosulfan, dacthal, and chlorothalonil in concentrations ranging from 0.07 to 2.4 ng/L. Of the OCCs, chlordane, hexachlorobenzene, and two polychlorinated biphenyl congeners were detected in only one snow sample each. Pesticides most frequently detected in rain were atrazine, carbaryl, and dacthal in concentrations from 3.0 to 95 ng/L. Estimated annual deposition rates in one of the parks were 8.4 microg/m2 for atrazine, 9.9 microg/m2 for carbaryl, and 2.6 microg/m2 for dacthal, of which >85% occurred during summer. p,p'-DDE and p,p' DDD were the most frequently detected OCCs in surface sediments from lakes. However, concentrations were low (0.12 to 4.7 microg/kg) and below levels at which harmful effects for benthic organisms are likely to be observed. DDD and DDE concentrations in an age-dated sediment core suggest that atmospheric deposition of DDT and its degradates, and possibly other banned OCCs, to high elevation areas have been decreasing since the 1970s. Dacthal and endosulfan sulfate were present in low concentrations (0.11 to 1.2 microg/kg) and were the only CUPs detected in surface sediments. Both pesticides were frequently detected in snow, confirming that some CUPs entering high-elevation aquatic environments through atmospheric deposition are accumulating in lake sediments and potentially in aquatic biota as well. PMID- 17285236 TI - Dioxin and dioxin-like activity in sediments of the Belgian coastal area (Southern North Sea). AB - Dioxin and dioxin-like activity in sediments of the North Sea, along the Belgian coast, was assessed with the bioassay CALUX (Chemically Activated LUciferase gene eXpression). Crude extracts of the samples as well as the dioxin fraction (PCDD/Fs) obtained after a thorough clean-up procedure were analyzed with the CALUX method. When analyzing the cleaned extract, a general low contamination level is observed (around 0.1 pg CALUX-TEQ/g sediment), except at the mouth of the two main rivers-the Yser and the Scheldt-where concentrations measured are about 100 times higher (10-42 pg CALUX-TEQ/g sediment). Much higher potencies are measured for the crude extracts compared to the cleaned ones. In the crude extracts, the highest dioxin-like activities were again observed at the mouth and outflow of the two rivers (600-7200 pg CALUX-TEQ/g sediment). These activities are at least two orders of magnitude higher than the ones found at the coastal and sea stations (1.3-45 pg CALUX-TEQ/g sediment). The difference in activity between cleaned and crude sediment extracts is due to the presence of dioxin-like compounds such as, for example, non-ortho and mono-ortho polychlorinated biphenyls and polybrominated dioxins, but also to PAHs. The percentage of five major PAHs in the crude samples at the river mouths, when using the average activities in those samples, varies between 25% and 50%. PMID- 17285237 TI - Suppression of endogenous antioxidant enzymes by 2,3,7,8-tetrachlorodibenzo-p dioxin-induced oxidative stress in chicken liver during development. AB - Domestic chickens (Gallus gallus) are an excellent model in which to evaluate developmental toxicity and oxidative stress because of their high sensitivity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The goal of this study was to measure the effects of environmentally relevant doses of TCDD on endogenous hepatic antioxidant enzyme activity in hatchling chickens. The vehicle (sunflower oil) or 2, 20, or 200 pg/g TCDD was injected into chicken eggs before incubation. On hatching, livers were harvested and quickly frozen. The changes in activity of antioxidant enzymes, including glutathione peroxidase (GPx), glutathione reductase (GRx), copper zinc superoxide dismutase (SOD), and catalase (CAT) were determined as indicators of oxidative stress. TCDD exposure was associated with a significant suppression of the activities of the protective endogenous enzymes GPx, GRx, and SOD in the liver, even at the lowest dose. CAT activity was also suppressed, but not significantly. The measured decreases were 37% to 63% for GPx, 50% to 58% for GRx, 30% to 40% for SOD, and 16% to 24% for CAT. Noncomplex dose-response relationships were evident in GPx and GRx, whereas SOD and CAT curves were U-shaped. These results demonstrate that a decreased ability to scavenge reactive oxygen species may result from developmental TCDD exposure at very low doses, contributing to oxidative stress and thus to the embryotoxicity of TCDD. PMID- 17285238 TI - Accumulation of organotin compounds in tissues and organs of stranded whales along the coasts of Thailand. AB - Concentrations of butyltin (BT) and phenyltin (PT) compounds were measured in organs and tissues of five species of whales (Bride's whale [Balaenoptera edeni], false killer whale [Pseudorca crassidens], pygmy sperm whale [Kogia breviceps], short-finned pilot whale [Globicephala macrorhynchus], and sperm whale [Physeter macrocephalus]) found stranded on the coasts of Thailand. The mean concentrations of BTs in various whales were in the range of 0.157 to 1.03 mg kg(-1 )wet weight, which were higher levels than the reported concentrations in whales from other countries. PT concentrations were also detected in the range of 0.022 to 1.14 mg kg(-1) wet weight. The concentrations of BTs and PTs in whales were higher than those in mussels from the coastal area of Thailand. Concentrations of tributyltin (TBT) and triphenyltin (TPT) compounds in whale organs and tissues were also compared, and it was found that TBT concentrations were generally higher in liver and lower in lung. TPT concentrations were higher in liver and blubber and lower in lung. Ratios of TBT degradation products in whale liver, namely monobutyltin (MBT) and dibutyltin (DBT), were higher than the ratios of TBT. TPTs in liver were found to be dominant among PTs. The patterns of BTs and PTs in false killer whale liver were different from those in the other whales by cluster analysis. Their concentrations in false killer whales were the highest among all whales in this study. False killer whales feed on squid and large pelagic fish containing higher concentrations of organotin (OT) compounds, so the differences in patterns and concentrations of OTs in liver between false killer whales and the other whales may be caused by difference in diet. PMID- 17285239 TI - Small animal absorbed radiation dose from serial micro-computed tomography imaging. AB - PURPOSE: To determine the radiation dose to mouse cancer xenografts from serial micro-computed tomography (CT) examinations. PROCEDURES: A nude mouse with a 15 mm subcutaneous pancreatic cancer xenograft in the rightflank was used. Radiation exposure to the subcutaneous tumor and the mouse pancreas (to simulate an orthotopic pancreatic tumor model) was measured using lithium fluoride thermoluminescent dosimeters. Ultrafast micro-CT was performed using 80 kVp, 0.26 mA, 0.156 mm slice thickness, 256 slices, 0.7 mm Al filtration, and 60-second image acquisition time (15 mA second). Micro-CT imaging acquisitions were repeated four times. RESULTS: We measured consistently low tumor doses (0.014 to 0.02 Gy; average=0.017 Gy) per scan. Orthotopic doses in the region of the pancreas were also consistently low (0.014 to 0.018 Gy; average=0.016 Gy) per scan. CONCLUSIONS: Radiation doses delivered during ultrafast micro-CT serial imaging in the mouse are low and are likely below the threshold to affect tumor growth. PMID- 17285240 TI - Assessment of the contribution of the LOC387715 gene polymorphism in a family with exudative age-related macular degeneration and heterozygous CFH variant (Y402H). AB - Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly population in developed countries. The etiology of AMD is not completely understood but environmental and genetic factors have been implicated in the disease. Recently it has been documented that variations in the complement factor H (CFH) and LOC 387715 genes are the major risk factors that predispose individuals to dry and wet AMD. To investigate further the genetic contribution to AMD, we have analyzed the LOC 387715 gene in a non-smoking family with an exudative AMD and a heterozygous mutation (Y402H) in the CFH gene. Direct sequencing of the amplified product of exon 1 of the LOC 387715 gene identified a previously reported missense mutation (A69S) in this family. The affected individual is homozygous for the mutation and this sequence alteration was not identified in six age-matched controls. On the basis of this and other results it is tempting to speculate that the combined effect of variants in the CFH and LOC 387715 genes may contribute to the AMD phenotype in this family. Further studies on these and other susceptibility genes may provide clues on variable phenotypes, new preventive strategies and treatment options for AMD. PMID- 17285241 TI - Functional pathway characterized by gene expression analysis of supraclavicular lymph node metastasis-positive breast cancer. AB - The outcome of breast cancer patients with supraclavicular lymph node metastasis is generally poor, but some patients do survive for a long time. Consequently, the ability to predict the outcome is important in terms of choosing the appropriate therapy for breast cancer patients with supraclavicular lymph node metastasis. In this study, we attempted to identify functional pathways that determine the outcome of breast cancer patients with supraclavicular lymph node metastasis by profiling cDNA microarrays. Thirty-one breast cancer patients with supraclavicular lymph node metastasis without distant metastasis comprised the study cohort; these were divided into three groups based on prognosis - poor, intermediate, and good. Two functional pathways, the Wnt signaling pathway and the mitochondrial apoptosis pathway, were constructed using six genes (DVL1, VDAC2, BIRC5, Stathmin1, PARP1, and RAD21) that were differently expressed between the good and poor outcome groups. Our results indicate that these two functional pathways may play an important role in determining the outcome of breast cancer patients with supraclavicular lymph node metastasis. We also determined that immunohistostaining for the Stathmin1 gene product is a potential tool for predicting the outcome of breast cancer patients with supraclavicular lymph node metastasis. PMID- 17285242 TI - Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients. AB - Megaloblastic anaemia 1 (MGA1) is a rare autosomal recessive condition characterized by selective intestinal vitamin B12 malabsorption and proteinuria. More than 200 MGA1 patients have been identified worldwide, but the disease is relatively prevalent in Finland, Norway and several Eastern Mediterranean regions. MGA1 is genetically heterogeneous and can be caused by mutations in either the cubilin (CUBN) or the amnionless (AMN) gene. In the present study we investigated the molecular defect underlying MGA1 in nine Tunisian patients belonging to six unrelated consanguineous families. Haplotype and linkage analyses, using microsatellite markers surrounding both CUBN and AMN genes, indicated that four out of the six families were likely to be linked to the CUBN gene. Patients from these families were screened for the Finnish, Mediterranean and Arabian mutations already published. None of the screened mutations could be detected in our population. One family showed a linkage to AMN gene. Direct screening of the AMN gene allowed the identification of the c.208-2A>G mutation, previously described in a Jewish Israeli patient of Tunisian origin and in Turkish patients. This suggests that the c.208-2A>G mutation may derive from a single Mediterranean founder ancestor. For the last family, haplotype analysis excluded both CUBN and AMN genes, suggesting the existence of a third locus that may cause MGA1. PMID- 17285243 TI - Salmonellae and campylobacters in household and stray dogs in northern Taiwan. AB - Rectal swabs were collected from 437 household and 491 stray dogs in northern Taiwan from May 2003 to June 2005 to investigate the prevalence and antimicrobial susceptibilities of salmonellae and campylobacters. The results revealed that 2.1% of household dogs and 6.3% of stray dogs were positive for salmonellae, with Salmonella Duesseldorf being the most dominant serotype in both. Additionally, 2.7% of the household dogs and 23.8% of the stray dogs were positive for campylobacters. Campylobacter jejuni was the most prevalent species (86.8%), followed by C. upsaliensis (9.3%) and C. coli (3.9%). Both salmonella and campylobacter isolation rates from the stray dogs were significantly higher than those from the household dogs (p < 0.01). The susceptibility of 33 C. jejuni isolates to eight antimicrobials was studied by the E-test. A high rate of resistance was observed to azithromycin (93.9%), clindamycin (87.9%), erythromycin (81.8%), tetracycline (78.8%), chloramphenicol (69.7%), nalidixic acid (51.5%), gentamicin (33.3%), and ciprofloxacin (18.2%). The susceptibility of 40 Salmonella isolates to 15 antimicrobials was also studied by the disc diffusion method. All the Salmonella isolates were susceptible to ciprofloxacin and ceftriaxone. Resistance was observed most frequently to tetracycline (77.5%), chloramphenicol (52.5%), and ampicillin (50%). PMID- 17285244 TI - Effect of meiotic stages during in vitro maturation on the survival of vitrified warmed buffalo oocytes. AB - The present study was conducted to investigate the effect of meiotic stages during in vitro maturation (IVM) on the survival of vitrified-warmed buffalo oocytes, vitrified at different stages of IVM. Cumulus oocyte complexes obtained from slaughterhouse ovaries were randomly divided into 6 groups: control (non vitrified, matured for 24 h at 38 +/- 1 degrees C, 5% CO2 in humidified air), and those matured for 0 h (vitrified before IVM) or 6, 12, 18 and 24 h before vitrification. Cumulus oocyte complexes were vitrified in solution consisting of 40% w/v propylene glycol and 0.25 mol/L trehalose in phosphate-buffered saline supplemented with 4% w/v bovine serum albumin. Vitrified cumulus oocyte complexes were stored at -196 degrees C (liquid nitrogen) for at least 7 days and then thawed at 37 degrees C; cryoprotectant was removed with 1 mol/L sucrose solution. Cumulus oocyte complexes in the 0, 6, 12, 18 and 24 h groups were then matured for an additional 24, 18, 12, 6 and 0 h, respectively, to complete 24 h of IVM. Among the five vitrification groups, 89-92% of cumulus oocyte complexes were recovered, after warming, of which 84-91% were morphologically normal. Overall survivability of vitrified cumulus oocyte complexes was lower (p < 0.05) than that of non-vitrified cumulus oocyte complexes (94.5%). Survival rates of cumulus oocyte complexes matured 24 h prior to vitrification (61.3%) were higher (p < 0.05) than those matured for 12 h (46.7%), 6 h (40.6%) and 0 h (37.6%). Nuclear status following 24 h IVM was assessed. A higher proportion of non-vitrified (control) oocytes (72.7%) reached metaphase II (M-II) stage in control than oocytes vitrified for 24 h (60.0%), 18 h (54.4), 12 h (42.3%), 6 h (33.3%) and 0 h (31.6%) (p < 0.05). The results suggest that length of time in maturation medium prior to vitrification influences post-thaw survivability of buffalo oocytes; longer intervals resulted in higher survival rates. PMID- 17285245 TI - Slide enzyme-linked immunosorbent assay for the diagnosis of Babesia bigemina infection in bovines. AB - A slide enzyme-linked immunosorbent assay (SELISA) for the diagnosis of Babesia bigemina infection in cattle was standardized. Acetone-fixed whole Babesia bigemina-infected erythrocytes on micro-slides were immunoreacted with bovine serum samples followed by antibovine horseradish peroxidase conjugate and developed using diaminobenzidine tetrahydrochloride as a substrate. The positive immunoreactivity (staining pattern) was visualized in the form of dark brown piroplasms. Using the laboratory-standardized SELISA with a sensitivity of 94.4%, the seroprevalence of babesiosis was studied in cattle from two endemic areas of the disease. In comparison to IFAT, SELISA detected higher number of serum samples positive for bovine babesiosis. PMID- 17285246 TI - The mycobiota and toxicity of equine feeds. AB - Feed contamination can lead to nutrient losses and detrimental effects on animal health and production. The purposes of this study were to investigate the mycobiota in equine mixed feeds and to determine natural contamination with aflatoxin B1 (AFB1) and fumonisin B1 (FB1). Fungal enumeration of equine feed samples was done. A commercially available enzyme-linked immunosorbent assay kit was applied to quantify AFB1 and FB1. A comparison between ELISA and HPLC was carried out. Feed mould counts ranged from <1 x 10(2) to 1 x 10(5) cfu/g. The most frequent genus isolated was Aspergillus (40.54%), followed by Penicillium (18.38%) and Fusarium (16.22%). The most prevalent Aspergillus sp. was A. flavus (36%). AFB1 values ranged between 0.01 and 99.4 microg/kg. FB(1) levels ranged between 0.01 and 7.49 microg/kg. HPLC and ELISA methods showed positive correlation for AFB1 and FB1 determinations (r = 0.9851 and r = 0.9791, respectively). The ELISA analytical method was efficient for AFB1 and FB1 detection. The scarcity of studies on natural fungal contamination and on the presence of AFB1 and FB1 in materials used as equine feed ingredients highlights the value and contribution of this study. PMID- 17285247 TI - Prevalence of hydatidosis in slaughtered herbivores in Qom province, central part of iran. PMID- 17285248 TI - Temporal and spatial distributions of foot-and-mouth disease under three different strategies of control and eradication in Colombia (1982-2003). AB - Outbreaks of foot-and-mouth disease (FMD) from January 1982 through December 2003 were used to examine variations in serotype- and species-specific risk for three control programmes in Colombia: (1982-1983) vaccination, using an aluminium hydroxide, saponin adjuvant, required but not enforced; (1984-1996) vaccination, using an oil double-emulsion adjuvant, required but not enforced; and (1997-2003) enforced vaccination, using an oil double-emulsion adjuvant, restricted animal movement enforced, and slaughter of infected animals. Hypotheses were tested for trend, cyclicity and seasonality in FMD occurrence, and for species- and serotype specific differences in morbidity and case-fatality. The spatial density of outbreaks was estimated by kernel smoothing. The frequency of outbreaks decreased most between 1984 and 1996 (p < 0.01) for serotype A and between 1997 and 2003 (p < 0.01) for serotype O. Outbreaks occurred in cycles of 3-4 years for both serotypes (p < 0.05). Morbidity was not significantly different in pigs from that in cattle for serotype A-associated outbreaks (p = 0.314), but was higher in pigs than in cattle (p = 0.019) for serotype O-associated outbreaks. For both serotypes, case-fatality was higher for pigs than for cattle (p < 0.009). Temporal variation in FMD incidence provided insight into the expected evolution of FMD control for countries with similar conditions and where FMD is endemic. PMID- 17285249 TI - Molecular in situ hybridization analysis of sheep and goat BAC clones identifies the transcriptional orientation of T cell receptor gamma genes on chromosome 4 in bovids. PMID- 17285250 TI - Complement receptor type 3 (CR3)- and Fc receptor (FcR)-mediated matrix metalloproteinase 9 (MMP-9) secretion and their intracellular signalling of bovine neutrophils. AB - Complement receptor type 3 (CR3)- and Fc receptor (FcR)-mediated metalloproteinase-9 (MMP-9) secretion and their intracellular signalling of bovine neutrophils were evaluated. Relative density of MMP-9 secreted by neutrophils stimulated with opsonized zymosan (OPZ, stimulant for CR3) was significantly (p < 0.05) increased when the OPZ concentration was increased from 0 to 0.4 mg/ml. Similar results were obtained for neutrophils stimulated with heat-aggregated IgG (Agg-IgG, stimulant for Fc receptor) at concentrations from 0 to 0.40 mg/ml. Preincubation of neutrophils with 1-30 nmol/L wortmannin (phosphoinositide 3-kinase inhibitor) resulted in inhibition of MMP-9 secretion induced by stimulation with OPZ and Agg-IgG in a concentration-dependent manner, 30 nmol/L wortmannin causing complete inhibition. Similarly, preincubation of neutrophils with 0-100 mumol/L genistein (tyrosine kinase inhibitor) also resulted in inhibition of OPZ- and Agg-IgG-induced MMP-9 secretion in a concentration-dependent manner, with 100 micromol/L genistein causing complete inhibition. Significant (p < 0.05) positive correlations were found between MMP-9 and luminal-dependent chemiluminescent response (LDCL) in the case of stimulation with OPZ (r = 0.754) and in the case of stimulation with Agg-IgG (r = 0.728). Our findings suggested that CR3 and FcR play a critical role in production of MMP-9 and may be regulated by intracellular signal transduction, including that by phosphoinositide 3-kinase (PI3K) and tyrosine kinase (TK). PMID- 17285251 TI - Problem-based learning at the receiving end: a 'mixed methods' study of junior medical students' perspectives. AB - Qualitative insights about students' personal experience of inconsistencies in implementation of problem-based learning (PBL) might help refocus expert discourse about good practice. AIM: This study explored how junior medical students conceptualize: PBL; good tutoring; and less effective sessions. METHODS: Participants comprised junior medical students in Liverpool 5-year problem-based, community-orientated curriculum. Data collection and analysis were mostly cross sectional, using inductive analysis of qualitative data from four brief questionnaires and a 'mixed' qualitative/quantitative approach to data handling. The 1999 cohort (end-Year 1) explored PBL, generated 'good tutor' themes, and identified PBL (dis)advantages (end-Year 1 then mid-Year 3). The 2001 cohort (start-Year 1) described critical incidents, and subsequently (end-Year 1) factors in less effective sessions. These factors were coded using coding-frames generated from the answers about critical incidents and 'good tutoring'. RESULTS: Overall, 61.2% (137), 77.9% (159), 71.0% (201), and 71.0% (198) responded to the four surveys, respectively. Responders perceived PBL as essentially process orientated, focused on small-groupwork/dynamics and testing understanding through discussion. They described 'good tutors' as knowing when and how to intervene without dominating (51.1%). In longitudinal data (end-Year 1 to mid-Year 3), the main perceived disadvantage remained lack of 'syllabus' (and related uncertainty). For less effective sessions (end-Year 1), tutor transgressions reflected unfulfilled expectations of good tutors, mostly intervening poorly (42.6% of responders). Student transgressions reflected the critical incident themes, mostly students' own lack of work/preparation (54.8%) and other students participating poorly (33.7%) or dominating/being self-centred (31.6%). CONCLUSION: Compelling individual accounts of uncomfortable PBL experiences should inform improvements in implementation. PMID- 17285252 TI - Accumulation of rare sex chromosome rearrangements in the African pygmy mouse, Mus (Nannomys) minutoides: a whole-arm reciprocal translocation (WART) involving an X-autosome fusion. AB - Although sex chromosomes are generally the most conserved elements of the mammalian karyotype, those of African pygmy mice show three extraordinary deviations from the norm: (a) asynaptic sex chromosomes, (b) multiple sex autosome fusions, and (c) modifications of sex determination in some populations/species. In this study we identified, in two sex-reversed females of Mus (Nannomys) minutoides, a fourth rare sex chromosome change: a spontaneous whole-arm reciprocal translocation (WART) between an autosomal Robertsonian pair Rb(13.16) and the sex-autosome fusion Rb(X.1). This represents one of the very few reported cases of WARTs in natura within mammals, and is the first one to involve sex chromosomes. Hence, this finding offers new insights into the mechanisms of chromosomal differentiation in African pygmy mice, as WARTs may have contributed to the extensive diversity not only of autosomal Robertsonian fusions, but also of sex-autosome translocations. More widely, these results provide additional support to previous studies on the house mouse and the common shrew which indirectly inferred the role of WARTs in their karyotypic evolution, and may even help to understand how the fascinating 10 sex chromosome chain of the platypus might have evolved. This accumulation of rare sex chromosome changes in single specimens is, to our knowledge, exceptional among mammals. PMID- 17285253 TI - B chromosomes of B. dichromosomatica show a reduced level of euchromatic histone H3 methylation marks. AB - B chromosomes (Bs) are dispensable, less-transcriptionally active components of the genomes of numerous species. Little information is available on the chromatin composition of Bs and whether it differs in any way from that of the A chromosomes. Methylated isoforms of histone H3 are of particular interest because of their role in eu/heterochromatin formation. Immunofluorescence using site specific antibodies demonstrates that the chromatin in A and both types of Bs of B. dichromosomatica differs markedly in euchromatic histone H3 methylation marks. While A chromosomes are labelled brightly, the micro B and large B chromosomes are faintly labelled with antibodies against H3K4me2/3, H3K9me3 and H3K27me2/3. The heteropycnotic, tandem-repeat enriched micro Bs were even less labelled with euchromatic histone H3 methylation marks than large Bs, most probably due to different DNA composition. No differences in immunolabelling intensity between A and B chromosomes were found as to the heterochromatic marks H3K9me1/2 and H3K27me1, indicating that Bs are not additionally labelled by heterochromatin typical histone H3 modifications. Analysis of DNA replication timing suggests that micro Bs are replicating throughout S-phase. PMID- 17285254 TI - The aero-geochemistry of cities and regions. PMID- 17285255 TI - Characteristics of hazardous airborne dust around an Indian surface coal mining area. AB - Surface coal mining creates more air pollution problems with respect to dust than underground mining . An investigation was conducted to evaluate the characteristics of the airborne dust created by surface coal mining in the Jharia Coalfield. Work zone air quality monitoring was conducted at six locations, and ambient air quality monitoring was conducted at five locations, for a period of 1 year. Total suspended particulate matter (TSP) concentration was found to be as high as 3,723 microg/m(3), respirable particulate matter (PM10) 780 microg/m(3), and benzene soluble matter was up to 32% in TSP in work zone air. In ambient air, the average maximum level of TSP was 837 microg/m(3), PM10 170 microg/m(3) and benzene soluble matter was up to 30%. Particle size analysis of TSP revealed that they were more respirable in nature and the median diameter was around 20 microm. Work zone air was found to have higher levels of TSP, PM10 and benzene soluble materials than ambient air. Variations in weight percentages for different size particles are discussed on the basis of mining activities. Anionic concentration in TSP was also determined. This paper concludes that more stringent air quality standards should be adopted for coal mining areas and due consideration should be given on particle size distribution of the air-borne dust while designing control equipment. PMID- 17285256 TI - Chemical constituents of fugitive dust. AB - Wind erosion selectively winnows the fine, most chemically concentrated portions of surface soils and results in the inter-regional transport of fugitive dust containing plant nutrients, trace elements and other soil-borne contaminants. We sampled and analyzed surface soils, sediments in transport over eroding fields, and attic dust from a small area of the Southern High Plains of Texas to characterize the physical nature and chemical constituents of these materials and to investigate techniques that would allow relatively rapid, low cost techniques for estimating the chemical constituents of fugitive dust from an eroding field. From chemical analyses of actively eroding sediments, it would appear that Ca is the only chemical species that is enriched more than others during the process of fugitive dust production. We found surface soil sieved to produce a sub-sample with particle diameters in the range of 53-74 microm to be a reasonably good surrogate for fugitive dust very near the source field, that sieved sub-samples with particle diameters <10 microm have a crustal enrichment factor of approximately 6, and that this factor, multiplied by the chemical contents of source soils, may be a reasonable estimator of fugitive PM(10) chemistry from the soils of interest. We also found that dust from tractor air cleaners provided a good surrogate for dust entrained by tillage and harvesting operations if the chemical species resulting from engine wear and exhaust were removed from the data set or scaled back to the average of enrichment factors noted for chemical species with no known anthropogenic sources. Chemical analyses of dust samples collected from attics approximately 4 km from the nearest source fields indicated that anthropogenic sources of several environmentally important nutrient and trace element species are much larger contributors, by up to nearly two orders of magnitude, to atmospheric loading and subsequent deposition than fugitive dust from eroding soils. PMID- 17285257 TI - Characterisation of indicator organisms and pathogens in domestic greywater for recycling. AB - Greywater from baths, showers and washbasins was collected separately from all other domestic wastewater at a university block of flats with a dual reticulation system and analysed for a range of contaminants including indicator organisms and pathogens. Greywater flow and temperature were also monitored and a diurnal variation was observed. Physical and chemical water quality parameters were similar to previously published data, although measured COD and BOD levels appeared to be lower, possibly due to settlement or biodegradation in the storage tanks. Plate counts and indicator organism concentrations were consistently high suggesting a high level of human bacterial contamination necessitating biological treatment and disinfection if the water is to be used for recycling. However, these high levels of indicator organisms did not correlate to pathogen presence and should not be used as pathogen indicators in greywater. One positive count of Salmonella veltereden was observed as well as low levels of Giardia. Cryptosporidium, Escherichia coli O157:H7, enteroviruses and Legionella were not identified in any of the samples. The research also highlighted a number of problems with the complexity of this type of sampling programme, such as identifying the most likely time to isolate pathogens and analysing an 'unusual' water source. PMID- 17285258 TI - Multivariate patterns of antioxidative and photoprotective defence compounds in spruce needles at two central European forest sites of different elevation. AB - In this work we measured a set of antioxidative and photoprotective compounds (chlorophylls, carotenoids, tocopherol, ascorbate and glutathione), which were suggested previously as stress markers in conifer needles, at two spruce forest sites at different elevation in Saxony, Germany. Most variables differed significantly between current and 1-year-old needles, but only the content of the xanthophyll cycle per mg total chlorophyll and the oxidation state of glutathione were significantly different between the sites. We applied principal component analysis (PCA) to address the question if underlying accumulated variables are similar to the ones found in spruce needles across Alpine elevation profiles and/or for pines in Mediterranean ecosystems. Four principal components (accumulated variables, PC) representing 68% of the total variance of the dataset were extracted. PC 1 encompassed total chlorophyll, lutein, and beta-carotene contents, PC 2 combined the epoxidation state of xanthophylls, ascorbate content and redox state, and glutathione content, PC 3 represented the content of xanthophylls and the redox state of glutathione, and PC 4 encompassed the content of alpha-carotene and the epoxidation state of xanthophylls. Only PC 3 was significantly different between sites. The PCA structure shows many similarities to corresponding findings in studies on spruce in mountain forests in the Alps and pines in Mediterranean systems. This corroborates the interpretation of PCs as indicative for underlying physiological processes. However, separation of the two investigated sites by PCs was in the present case study not superior to the separation by single input variables. PMID- 17285259 TI - Types of ectomycorrhiza of mature beech and spruce at ozone-fumigated and control forest plots. AB - In the Kranzberg forest near Freising (Germany) a novel "Free-Air Canopy O3 Exposure" system has been employed for analysing O3-induced responses from sub cellular to ecosystem levels that are relevant for carbon balance and CO2 demand of 60-year-old beech trees. The below-ground ectomycorrhizal community was studied in two-fold ambient O3 concentrations (five cores per sampling) and in a control plot with an ambient O3 concentration (four cores per sampling). Five samplings were taken throughout two vegetation seasons (2003 and 2004). Types of ectomycorrhiza were determined by their morphological, anatomical and molecular characteristics and quantified by counting. The total number of mycorrhizal fine roots was higher at the fumigated plot as compared with the control site. The numbers of ectomycorrhizal types at the fumigated and control plots were 28 and 26, respectively. Cenococcum geophilum was present in all soil cores at all sampling times with a significant increase in abundance under ozone-fumigated trees. Other mycorrhizal types present at higher abundance at the fumigated than at the control plot were identified as Russula densiflora, R. fellea, R. illota, Tuber puberulum, Lactarius sp. 2 and Russula sp. 2. Some mycorrhizal types were present exclusively at the fumigated plot (Fagirhiza fusca, F. setifera, Lactarius acris, Piceirhiza nigra and Russula sp. 1). A possible ecological role for the abundant types of ectomycorrhiza and their putative application in bio indication is discussed. PMID- 17285261 TI - Dietary fiber intake and ovarian cancer risk: a prospective cohort study. AB - There is some evidence from case-control studies that dietary fiber intake might be inversely associated with ovarian cancer risk, but there are limited prospective data. Therefore, we examined ovarian cancer risk in association with intake of dietary fiber in a prospective cohort of 49,613 Canadian women enrolled in the National Breast Screening Study (NBSS), who completed a self-administered food frequency questionnaire between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. Data from the food frequency questionnaire were used to estimate intake of total dietary fiber, of fiber fractions, and of fiber from various sources. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between energy-adjusted quartile levels of fiber intake and ovarian cancer risk. During a mean 16.4 years of follow-up, we observed 264 incident ovarian cancer cases. Total dietary fiber and fiber fractions were not associated with ovarian cancer risk in this study population. PMID- 17285262 TI - The black:white disparity in breast cancer mortality: the example of Chicago. AB - OBJECTIVE: The black:white disparity in breast cancer mortality has been increasing in the U.S. In order to gain insight into this disparity in Chicago, we examined mortality data together with other important measures associated with breast cancer. METHODS: Trends in black:white female breast cancer mortality, incidence, stage at diagnosis, and mammography screening in Chicago were examined using data from the Illinois State Cancer Registry, Illinois Department of Public Health Vital Records, and the Illinois Behavioral Risk Factor Surveillance System. RESULTS: The breast cancer mortality rate for black women in Chicago for 1999-2003 was 49% higher than that of white women, but the disparity is a recent phenomenon that is increasing rapidly. In 2003 the black rate was 68% higher than the white rate. Mortality rates were similar in the 1980's and only started to diverge in the 1990's as a result of a sharp improvement in mortality among white women contrasted with no improvement for black women. This lack of progress for black women is perplexing given that self-reported mammography screening rates have been the same for blacks and whites in Chicago since at least 1996 and that the early detection of breast cancer for black women has been increasing. CONCLUSIONS: There has been no improvement in mortality from breast cancer for black women in Chicago in 23 years. This study, along with a review of the literature, lends support to the hypothesis that the disparities in breast cancer mortality are due to differential access to mammography, differential quality in mammography, and differential access to treatment for breast cancer. Fortunately, all three are amenable to intervention, which would help ameliorate this unacceptable disparity. PMID- 17285263 TI - A comparison of echocardiographic and electron beam computed tomographic assessment of aortic valve area in patients with valvular aortic stenosis. AB - The purpose of this study was to compare electron beam computed tomography (EBT) with transthoracic echocardiography (TTE) in determining aortic valve area (AVA). Thirty patients (9 females, 21 males) underwent a contrast-enhanced EBT scan (e Speed, GE, San Francisco, CA, USA) and TTE within 17 +/- 12 days. In end inspiratory breath hold, a prospectively ecg-triggered scan was acquired with a beam speed of 50-100 ms, a collimation of 2 x 1.5 mm and an increment of 3.0 mm. The AVA was measured with planimetry. A complete TTE study was performed in all patients, and the AVA was computed using the continuity equation. There was close correlation between AVA measured with EBT and AVA assessed with TTE (r = 0.60, P < 0.01). The AVA measured with EBT was 0.51 +/- 0.46 cm(2 )larger than the AVA calculated with TTE measurements. EBT appeared to be a valuable non-invasive method to measure the AVA. EBT measures the anatomical AVA, while with TTE the functional AVA is calculated, which explains the difference in results between the methods. PMID- 17285264 TI - Comparison of different MRI techniques for the assessment of thoracic aortic pathology: 3D contrast enhanced MR angiography, turbo spin echo and balanced steady state free precession. AB - PURPOSE: The purpose of this study was to compare two non-contrast 2D techniques with the current contrast-enhanced MRI standard 3D technique for the routine assessment of thoracic aortic pathologies. METHODS: One hundred patients with suspected or known thoracic aortic diseases were examined with a 1.5 T scanner using 2D turbo spin echo (TSE), 2D balanced steady state free precession (balanced SSFP) and 3D contrast-enhanced MR angiography (CE-MRA). The diameters of the aorta at predefined levels were measured. The feasibility to visualize the aortic root and supra-aortic branches was tested. All morphologic abnormalities of the aorta, the aortic wall and the aortic valve, as well as image quality of TSE and balanced SSFP influencing the diagnosis were analysed. RESULTS: Compared to CE-MRA, balanced SSFP and TSE allowed for the detection of a significantly higher number of relevant pathologies (thickened aortic wall and signs of emergency) in less time. No significant differences were found among the sequences for the identification of aneurysms, dissection membranes and thrombi. No single technique was able to address all clinically relevant issues. TSE was associated with a better image quality compared to balanced SSFP, which however did not translate into a significantly improved diagnostic accuracy. CONCLUSION: The total number of pathologic findings was higher using 2D TSE and balanced SSFP when compared to 3D CE-MRA. None of the techniques applied could address all clinically relevant issues. The major drawback of TSE is its relatively long scanning time while balanced SSFP is associated with more artifacts. PMID- 17285265 TI - Renal perforation and retroperitoneal hematoma: an unusual complication following cardiac catheterization. AB - Retroperitoneal hematoma (RPH) is a well-recognised, albeit rare complication of percutaneous transfemoral cardiac catheterization. We describe an unusual case of renal perforation and RPH following transfemoral cardiac catheterization for endomyocardial biopsy. Diagnosis was made based on multidetector computed tomography (MDCT) which clearly depicted active renal hemorrhage in short acquisition time. The case expands the spectrum of possible complications of percutaneous transfemoral cardiac catheterization and illustrates the usefulness MDCT in quickly and adequately detecting RPH. PMID- 17285266 TI - Pharma-Planta: road testing the developing regulatory guidelines for plant-made pharmaceuticals. AB - Significant advances over the last few years have seen plant-made pharmaceuticals (PMPs) move from the exploratory research phase towards clinical trials, with the first commercial products for human use expected to reach the market by 2009. Europe has yet to witness the commercial application of PMP technology, although at least one product has begun phase II clinical trials with others following close behind. These emerging products are set to challenge the complex and overlapping regulations that currently govern GM plants and 'conventional' pharmaceutical production. The areas of responsibility are being mapped out between the different EU regulatory agencies, with specific guidelines currently being drawn up for the regulation of PMPs. This article discusses issues surrounding the development of robust risk-assessment and risk-management practices based on health and environmental impact, while working with EU regulatory authorities to ensure appropriate regulatory oversight. PMID- 17285267 TI - Personality and fatigue in patients with benign or malignant breast disease. AB - GOALS OF WORK: The aim of the study was to examine the role of five general personality traits in fatigue in a group of patients with breast cancer (BC) and a group with benign breast problems (BBP). MATERIALS AND METHODS: Of the 304 participating women, 127 patients had BC and 177 BBP. A fatigue scale was completed before diagnosis and 1, 3, and 6 months after diagnosis (benign patients) or surgical treatment (BC patients). A personality questionnaire (NEO FFI) and a depression scale (CES-D) were completed before diagnosis. MAIN RESULTS: The BC group was less tired before diagnosis, more tired 1 month after diagnosis, and equally tired 3 and 6 months after diagnosis. In the total group, women were more tired over time when they were more neurotic, less agreeable, or more introverted. After controlling for depressive symptoms, demographics, and medical factors, baseline depressive symptoms (beta = 0.29, p < 0.05), neuroticism (beta = 0.29, p < 0.05), and extraversion (beta = -0.25, p < 0.05) predicted fatigue 6 months later. After also including baseline fatigue, only neuroticism (beta = 0.22, p < 0.05) and baseline fatigue (beta = 0.79, p < 0.001) predicted fatigue. CONCLUSIONS: Personality is more strongly related to fatigue than demographics, the diagnosis cancer, receiving cancer treatment, and baseline depressive symptoms and fatigue. When replicated, screening and treating women who are at risk to experience high levels of fatigue is recommended. PMID- 17285268 TI - Sporadic and multiple neurofibromas in the head and neck region: a retrospective study of 33 years. AB - The neurofibroma occurs as isolated or multiple lesions frequently associated with neurofibromatosis type 1 (NF-1). The aim of this study was to analyze the clinical and histopathological features of neurofibromas, particularly the plexiform variant, in the skin and oral mucosa, discussing their pathogenesis as well as clinical management of isolated lesion unassociated with NF1. The clinicopathologic features of 66 neurofibromas in the head and neck region diagnosed at the pathology laboratories of the Bauru Dentistry School and Lauro de Souza Lima Research Institute from 1970 to 2003 were reviewed. The clinical data, therapy, and follow-up information were obtained from the medical records. The results showed a high frequency of cutaneous lesions (81.8%) occurring mainly in females older than 40 years. Isolated neurofibromas were found in 51.2% of patients, and multiple lesions were often associated with the NF-1. The histopathological analysis demonstrated that diffused neurofibromas occur more frequently than the plexiform type. However, one case of plexiform neurofibroma was detected in the oral mucosa as an isolated lesion non-associated with the NF 1. The indolent clinical behavior of isolated neurofibromas in the head and neck region and the absence of NF-1 association reinforce that sporadic lesion could be hyperplastic or hamartomatous rather than neoplastic in nature. PMID- 17285269 TI - The effect of bee propolis on recurrent aphthous stomatitis: a pilot study. AB - Recurrent aphthous stomatitis (RAS) is a common, painful, and ulcerative disorder of the oral cavity of unknown etiology. No cure exists and medications aim to reduce pain associated with ulcers through topical applications or reduce outbreak frequency with systemic medications, many having serious side effects. The purpose of this pilot study was to evaluate the potential of a product to reduce the number of outbreaks of RAS ulcers. Propolis is a bee product used in some cultures as treatment for mouth ulcers. In this randomized, double-blind, placebo-controlled study, patients were assigned to take 500 mg of propolis or a placebo capsule daily. Subjects reported a baseline ulcer frequency and were contacted biweekly to record recurrences. Data were analyzed to determine if subjects had a decrease of 50% in outbreak frequency. The data indicated a statistically significant reduction of outbreaks in the propolis group (Fisher's exact test, one sided, p = 0.04). Patients in the propolis group also self reported a significant improvement in their quality of life (p = 0.03). This study has shown propolis to be effective in decreasing the number of recurrences and improve the quality of life in patients who suffer from RAS. Propolis should be evaluated further in a larger sample clinical trial. PMID- 17285270 TI - A rare case of progressive bilateral congenital abduction contracture with shoulder dislocations treated with proximal deltoid release. AB - The contracture of the deltoid muscle is an uncommon disorder. Amongst the various causes reported, post intramuscular injection and trauma leading to the fibrosis of the muscle are common. However, congenital cases are extremely rare. We report a case of congenital progressive bilateral abduction contracture left untreated for a long time leading to anteroinferior subluxation. A proximal release was performed with satisfactory outcome on both sides. PMID- 17285271 TI - [Dual-source CT in chest pain diagnosis]. AB - BACKGROUND: With the depiction of pulmonary arteries, coronary arteries, and the aorta, CT angiography of the chest offers a comprehensive diagnostic work-up of unclear chest pain. The aim of this study was to assess the diagnostic accuracy of dual-source CT in this patient group. MATERIALS AND METHODS: A total of 47 patients suffering from unclear chest pain were examined with a Siemens Somatom Definition. Volume and flow of contrast media (Ultravist, Schering) were adapted to the body weight. The examinations were evaluated with regard to image quality and contrast opacification and to the diagnostic accuracy with reference to the final clinical diagnosis. RESULTS: Adequate contrast opacification was achieved in all examinations. The depiction of the coronary arteries was diagnostic in all cases. The cause of chest pain could be identified in 41 cases. Among the diagnoses were coronary and myocardial pathologies, valvular disease, aortic aneurysms and dissections, pulmonary embolism, and pneumonic consolidation. CONCLUSION: DSCT angiography of the chest offers a very good image quality even at high heart rates so that a high diagnostic accuracy is achieved in patients with acute chest pain. PMID- 17285272 TI - [Dual-source cardiac CT imaging with improved temporal resolution: Impact on image quality and analysis of left ventricular function]. AB - In a newly developed dual-source computed tomography system (DSCT) the relation of heart rate and image quality and the possible advantages of the system's superior temporal resolution in the evaluation of left ventricular parameters as compared to results of cardiac magnetic resonance imaging (MRI) were assessed. Coronary CT angiography was performed using a DSCT (Somatom Defintion, Siemens Medical Solutions, Forchheim, Germany) in 21 patients (mean age 62+/-8; 15 male, 6 female). Image quality of the coronary arteries, the heart valves, and the left ventricular myocardium was assessed using a three-point grading scale. Ten of these patients also underwent cardiac MRI for the assessment of left ventricular function, using a SSFP (steady-state free precession) sequence. Left ventricular ejection fractions (LV-EF), the end-systolic volumes (ESV), and the end-diastolic volumes (EDV) were measured employing MRI and DSCT datasets. The image quality ratings for the coronary arteries at the optimal reconstruction interval were diagnostic even in patients with high heart rates (1.42+/-0.49). Analysis of global LV function using DSCT quantified from CTA datasets showed a good correlation with results of cardiac MRI [EF: r=0.75 (p=0.01); ESV: r=0.72 (p=0.19); EDV: r=0.71 (p=0.02)]. The dual-source CT system offers robust image quality of the coronary arteries, independent of the heart rate, and provides combined diagnostic imaging of coronary arteries, the heart valves, the myocardium, and the global left ventricular function. PMID- 17285273 TI - [Pathophysiology, neurology and diagnostic radiology of degenerative diseases of the lumbar spine]. AB - Degenerative diseases of the lumbar spine have a high medical and socioeconomic impact. The leading symptom is back pain, but there are many reasons for this. The aim of this paper is to describe the pathogenesis of degenerative diseases of the lumbar spine and their clinical symptoms in relation to the functional anatomy and biomechanics of the spine. Discs, vertebral facet joints, osseous and ligamentous structures as well as the erector trunci muscles are a functional unit. Progressive degenerative changes of the discs induce bone overgrowth and ligamentous thickening, affect the orientation of the vertebral facet joints and change the pressure, tension and shear forces of the spine. The different radiological diagnostic tools are presented and discussed according to the different degenerative diseases of the lumbar spine. PMID- 17285274 TI - Sestamibi and FDG-PET scans to support diagnosis of jaw osteonecrosis. AB - Osteonecrosis of the maxillary or mandibular bone is an infrequent but often severe event occurring in patients who undergo prolonged treatment with bisphosphonates. Histology is in some cases mandatory to differentiate it from neoplastic osteolysis, but a biopsy can further contribute to bone damage. Functional imaging obtained by a tracer that shows oncotropic properties, such as Tc99m-sestamibi, in comparison to a non-tumor-specific substance such as FDG-PET, can support the differential diagnosis, thus avoiding invasive procedures. Four patients affected by multiple myeloma and jaw osteonecrosis were prospectively evaluated by sestamibi and FDG-PET scans. Local diagnosis was performed by clinical, radiological and, in some cases, histological evaluations. Each patient was studied by Tc99m-sestamibi, performed by planar anterior and posterior whole body scans and SPECT of the head and neck, and by PET/CT. Two nuclear medicine physicians, unaware of the final diagnosis, reviewed the images. No sestamibi uptake was evident in the four patients with jaw osteonecrosis, while FDG-PET/CT showed focal uptake in all of them. Our study suggests that the combined use of sestamibi scintigraphy and FDG-PET/CT could support the clinical diagnosis of oral osteonecrosis avoiding the risks of a surgical biopsy. Studies on higher number of patients are necessary to validate these preliminary observations. PMID- 17285275 TI - Arteriovenous malformation of the mandible: a life-threatening situation. AB - Arteriovenous malformation (AVM) of the mandible is not only a rare entity, but also one that can be potentially life threatening due to massive haemorrhage. The authors describe three cases of children with AVM of the mandible. PMID- 17285276 TI - Diagnostic refinement of chronic myeloproliferative disorders and thrombocytoses of unknown origin by multiple RT-PCR and capillary electrophoresis of BCR-ABL rearrangements and JAK2 (V617F) mutation. AB - Detection of genetic markers improves diagnostic refinement of chronic myeloproliferative disorders (CMDs) and is helpful in discriminating reactive conditions mimicking CMDs such as reactive erythrocytosis and thrombocytosis. We set-up a multiplex real-time polymerase chain reaction assay followed by capillary electrophoresis, designed to simultaneously screen the two main genetic lesions associated with CMDs, i.e. the BCR-ABL fusion characteristic of chronic myeloid leukemia and the JAK2 V617F mutation that characterises polycythaemia vera and a proportion of cases of essential thrombocythemia and idiopathic myelofibrosis. The test was used in the diagnostic work-up of 50 patients with elevation of >or=2 myeloid cell types in their blood count at presentation and in 42 patients with isolated, non-reactive thrombocytosis. This approach refined diagnosis in 44 of 50 cases in the first series and in 22 of 42 cases with isolated thrombocytosis. We conclude that this non-isotopic and rapid assay amenable to automation may be adopted in routine genetic diagnosis of CMDs as well as for initial screening of thrombocytosis of unknown nature. PMID- 17285277 TI - Upregulation of antigen-processing machinery components at mRNA level in acute lymphoblastic leukemia cells after CD40 stimulation. AB - The development of immunotherapy in hematologic malignancies has been observed in the last few years. One of the approaches is the use of cancer vaccines based on leukemia-derived dendritic cells (DC). Recent studies from our laboratory and other laboratories have shown that CD40 stimulation improves leukemia cells immunogenicity and generates an antitumor immune response. The design of future cancer vaccines requires the knowledge concerning the function of dendritic cells including antigen processing. The aim of our present study was the assessment of antigen-processing machinery (APM) components in acute lymphoblastic leukemia (ALL) cells before and after CD40 stimulation at messenger RNA (mRNA) level. Twenty-five children with ALL were enrolled into the study. Leukemic cells were stimulated (or not) with CD40L and IL-4. Elements of the antigen-processing machinery (MB1, LMP2, LMP7, LMP10, TAP1, TAP2, calnexin, calreticulin, tapasin, ERp57, zeta, delta) were determined by real-time PCR technique. The expression of important costimulatory and adhesion molecules considered as DC markers (CD40, CD54, CD80, CD83, CD86) were determined at the mRNA (PCR) and protein (flow cytometry) levels. The following are the results of our study: (1) We noted an upregulation of all costimulatory and adhesion molecules at the mRNA and protein levels in ALL cells after the culture; (2) the significant rise in expression of nearly all APM components after CD40 stimulation was observed. This confirms specific stimulation of the antigen-processing system in ALL cells by CD40L. Future work should focus on the clinical significance of these findings for immunotherapy in leukemias. PMID- 17285278 TI - Successful treatment of avascular bone necrosis of the knee with neridronate: a case report. PMID- 17285279 TI - Evaluation of dose exposure in 64-slice CT colonography. AB - The radiation exposure of four different 64-slice MDCT-colonography (CTC) protocols was evaluated using an Alderson-Rando phantom. Protocols using 30 mAs (collimation 20 x 1.2 mm), 50 mAs (collimation 20 x 1.2 and 64 x 0.6 mm) and 80 mAs (20 x 1.2 mm) representing screening low-dose, routine, narrow collimation and oncologic staging setups were measured with an Alderson-Rando phantom (Alderson Research Laboratories Inc.). Scans were performed on a 64-row MDCT (SOMATOM Sensation 64, Siemens) simulating the prone and supine positions with a constant voltage of 120 kV. Dose values (male/female) were 2.5/2.9, 3.8/4.2, 4.2/4.5 and 5.7/6.4 mSv for 30, 50 (20 x 1.2 and 64 x 0.6 mm) and 80 mAs, respectively. Measurements showed an elevated dose for females (11.5% mean; compared to males). Use of narrow collimation combined with 50 mAs resulted in a small increase of dose exposure of 10.5 (male) and 7.1% (female). Gonad doses ranged from 0.9 to 2.6 mSv (male) and from 1.5 to 3.5 mSv (female). In all protocols, the stomach wall, lower colon, urinary bladder and liver were slightly more highly exposed (all <2.3 mSv) than the other organs, and the breast dose was <0.3 mSv in every setup. Values of radiation exposure in 64- and 16-slice CTC differ only marginally when using the narrow collimation. In 64-slice CTC, the use of narrow (64 x 0.6 mm) collimation shows slightly elevated dose values compared to wider (20 x 1.2 mm) collimation. PMID- 17285280 TI - One-molar gadolinium chelate (gadobutrol) as a contrast agent for CT angiography of the thoracic and abdominal aorta. AB - The aim of our study was to evaluate the use of a 1-molar gadolinium chelate (gadobutrol) as an alternative contrast medium for computed tomography angiography (CTA) exams of the aorta. CTA exams of the thoracic and/or abdominal aorta were performed on 15 patients with contraindications for the use of iodine who were not suitable for magnetic resonance examinations. The exams were performed with a 16-detector row scanner, injecting a mean dose of 0.37 mmol Gd/kg of body weight at a flow rate of 4 ml/s. Creatinine levels were obtained prior to the exam in patients with impaired renal function, and 24 and 48 h afterwards. The mean attenuation values obtained in the middle ascending and middle descending thoracic aorta were 202.3 and 216.8, respectively. The mean HU values of the abdominal aorta were 210.4 at the level of the renal arteries and 186.8 in the aortic bifurcation. All the exams were considered diagnostically adequate. No significant increase in serum creatinine was observed 24 and 48 h after the exam. We believe that gadobutrol could be an alternative contrast medium for CTA exams with 16-detector row scanners in patients with contraindications for iodinated contrast medium. PMID- 17285281 TI - Ectopic origin of bronchial arteries: assessment with multidetector helical CT angiography. AB - The purpose of this study was to determine non-invasively the frequency of ectopic bronchial arteries (BA) (i.e., bronchial arteries originating at a level of the descending aorta other than T5-T6 or from any aortic collateral vessel) on multidetector-row CT angiograms (CTA) obtained in patients with hemoptysis. Over a 5-year period (2000-2005), 251 consecutive patients with hemoptysis underwent multidetector-row CT angiography of the thorax. From this population, 37 patients were excluded because of a suboptimal CTA examination (n = 19), the presence of extensive mediastinal disease (n = 15) or severe chest deformation (n = 3) precluding any precise analysis of the bronchial arteries at CTA. Our final study group included 214 patients who underwent a thin-collimated CT angiogram (contrast agent: 300 to 350 mg/ml) on a 4- (n = 56), 16- (n = 119) and 64- (n = 39) detector-row scanner. The site of origin and distribution of bronchial arteries were analyzed on transverse CT scans, maximum intensity projections and volume-rendered images. The site of the ostium of a bronchial artery was coded as orthotopic when the artery originated from the descending aorta between the levels of the fifth and sixth thoracic vertebrae; all other bronchial arteries were considered ectopic. From the studied population, 137 (64%) patients had only orthotopic bronchial arteries, whereas 77 patients (36%) had at least one bronchial artery of ectopic origin. A total of 147 ectopic arteries were depicted, originating as common bronchial trunks (n = 23; 19%) or isolated right or left bronchial arteries (n = 101; 81%). The most frequent sites of origin of the 124 ostiums were the concavity of the aortic arch (92/124; 74%), the subclavian artery (13/124; 10.5%) and the descending aorta (10/124; 8.5%). The isolated ectopic bronchial arteries supplied the ipsilateral lung in all but three cases. Bronchial artery embolization was indicated in 26 patients. On the basis of CTA information, (1) bronchial embolization was attempted in 24 patients; it was technically successful in 21 patients (orthotopic BAs: 6 patients; orthotopic and ectopic BAs: 3 patients; ectopic BAs: 12 patients) and failed in 3 patients due to an instable catheterization of the ectopic BAs; the absence of additional bronchial arterial supply and no abnormalities of nonbronchial systemic arteries at CTA avoided additional arteriograms in these 3 patients; (2) owing to the iatrogenic risk of the embolization procedure of ectopic BAs, the surgical ligation of the abnormal vessels was the favored therapeutic option in 2 patients. This study enabled the depiction of ectopic bronchial arteries in 36% of the studied population, important anatomical information prior to therapeutic decision making. PMID- 17285282 TI - Pachydermoperiostosis-critical analysis with report of five unusual cases. AB - Pachydermoperiostosis (idiopathic hypertrophic arthropathy) {MIM 167100} is an uncommon disease characterized by unique phenotype (digital clubbing and pachydermia) and distinctive radiographic appearances (periostosis). Two families are reported that, in additional to the typical phenotype and radiographic characteristics of pachydermoperiostosis, show some rare and/or unusual, not yet reported, clinical findings. In the first family, distinctive features were severe progressive arthritis with villonodular involvement of the knees. The clinical course of the disease was much more severe than usually reported. The older brother was disabled at the age of 29 years. In the second family, the clinical history was exceptional, with unique early appearance of clinical signs. Pachydermoperiostosis is usually inherited as a dominant trait, but probable autosomal recessive inheritance has been reported. Also in the present families, autosomal recessive inheritance is likely, possibly explaining the severe clinical course of the disease. Differential diagnosis and the confusing nomenclature of pachydermoperiostosis are discussed. PMID- 17285283 TI - A rare type of ileal atresia due to intrauterine intussusception. AB - Intrauterine intussusception is an extremely rare cause of intestinal atresia. We report on a full-term neonate with clinical manifestations of intestinal obstruction two days after birth. The prenatal sonography at the late stage of pregnancy did not show any abnormality. The barium enema suggested distal intestinal obstruction. At surgery, a visible ileo-ileal intussusception resulting in ileal atresia was found. According to our knowledge, this presentation of ileal atresia did not fit into the present classification and have not yet been reported on. We present this rare type of ileal atresia due to intrauterine intussusception with operative evidence, which is the first case reported in the medical literature so far. PMID- 17285284 TI - Pleuropulmonary blastoma, a distinctive neoplasm of childhood: report of three cases. AB - BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare, aggressive dysontogenetic neoplasm affecting children. It was identified as a distinct entity by Manivel in 1988 and later subdivided into three types on the basis of the histological pattern, with increasing malignancy from type I (cystic) through type II (solid/cystic) to type III (solid). OBJECTIVE: To report on the imaging findings, clinical presentation, and differential diagnosis, mainly cystic malformations. MATERIALS AND METHODS: We evaluated three children, age 2-4 years, with PPB. RESULTS: One patient presented with unresolving pneumothorax and a multicystic mass, another with a mixed fluid/solid lesion, and the last with a solid heterogeneous mass. CONCLUSION: Despite its rarity, PPB should be considered in the evaluation of cystic or solid masses in children with respiratory distress. Plain film radiography alone is unable to distinguish between PPB and cystic malformations. CT represents the gold standard, although MRI can show the imaging features of solid enhancing nodules inside fluid-filled cavities, a mass causing lung compression, mediastinal shift, frequent pleural effusion, and no chest wall invasion. No preoperative imaging can reliably differentiate between congenital cystic lesions and PPB type I. PMID- 17285285 TI - Complexity in the cattle CD94/NKG2 gene families. AB - Natural killer cell responses are controlled to a large extent by the interaction of an array of inhibitory and activating receptors with their ligands. The mostly nonpolymorphic CD94/NKG2 receptors in both humans and mice were shown to recognize a single nonclassical MHC class I molecule in each case. In this paper, we describe the CD94/NKG2 gene family in cattle. NKG2 and CD94 sequences were amplified from cDNA derived from four animals. Four CD94 sequences, ten NKG2A, and three NKG2C sequences were identified in total. In contrast to human, we show that cattle have multiple distinct NKG2A genes, some of which show minor allelic variation. All of the sequences designated NKG2A have two tyrosine-based inhibitory motifs in the cytoplasmic domain and one putative gene has, in addition, a charged residue in the transmembrane domain. NKG2C appears to be essentially monomorphic in cattle. All of the NKG2A sequences are similar apart from NKG2A-01, which, in contrast, shares the majority of its carbohydrate recognition domain with NKG2-C. Most of the genes appear to generate multiple alternatively spliced forms. These findings suggest that the CD94/NKG2A heterodimers in cattle, in contrast to other species, are binding several different ligands. Because NKG2C is not polymorphic, this raises questions as to the combined functional capacity of the CD94/NKG2 gene families in cattle. PMID- 17285287 TI - Synthesis of chiral alpha-hydroxy amides by two sequential enzymatic catalyzed reactions. AB - Enantiomerically pure alpha-hydroxy amides have been prepared from the corresponding alpha-oxo esters by the use of a double sequence reaction involving in a first step the highly enantioselective Saccharomyces cerevisiae bioreduction and then in a second step, the resulting alpha-hydroxy esters followed a non enantiospecific lipase catalyzed aminolysis with n-butylamine reaction. In the first non-organic solvent process, the moistened baker's yeast reduced seven alpha-oxo esters with high conversions degree (93% for one substrate and >99% for the others) and high enantioselectivities [>99% for all the substrates except for ketopantoyl lactone, which gave 88% of enantiomeric excess (ee)]. At the same way, the isolated resulting chiral alpha-hydroxy esters were subjected to the second Candida antarctica lipase fraction B (CAL-B) catalyzed aminolysis in dioxane conducting to the corresponding chiral alpha-hydroxy amides with high conversions degree, between 88 and 99%. Both processes were carried out at 28-30 degrees C. PMID- 17285288 TI - A chimeric baculovirus displaying bovine herpesvirus-1 (BHV-1) glycoprotein D on its surface and their immunological properties. AB - The ability of a recombinant baculovirus containing the ectodomain of the mature sequence of glycoprotein D (gD) fused to the amino-terminus of baculoviral glycoprotein gp64 to display gD on its surface and to serve as an improved immunogen against bovine herpesvirus-1 was tested. The gD-gp64 fusion protein was correctly expressed on the virus particles as revealed by immunomicroscopy assays. Mice immunized with 5 x 10(8) plaque forming units developed antibodies that specifically reacted in an enzyme-linked immunosorbent assay with recombinant gD and whole bovine herpesvirus-1. These antibodies were able to neutralize bovine herpesvirus-1 in vitro, whereas those elicited by a version of gD expressed in Escherichia coli did not. Our data demonstrated that the display on the virion surface of recombinant baculovirus can provide a tool for the development of recombinant vaccines against bovine herpesvirus-1. PMID- 17285289 TI - Vaccination with p53 peptide-pulsed dendritic cells is associated with disease stabilization in patients with p53 expressing advanced breast cancer; monitoring of serum YKL-40 and IL-6 as response biomarkers. AB - p53 Mutations are found in up to 30% of breast cancers and peptides derived from over-expressed p53 protein are presented by class I HLA molecules and may act as tumor-associated epitopes in cancer vaccines. A dendritic cell (DC) based p53 targeting vaccine was analyzed in HLA-A2+ patients with progressive advanced breast cancer. DCs were loaded with 3 wild-type and 3 P2 anchor modified HLA-A2 binding p53 peptides. Patients received up to 10 sc vaccinations with 5 x 10(6) p53-peptide loaded DC with 1-2 weeks interval. Concomitantly, 6 MIU/m(2) interleukine-2 was administered sc. Results from a phase II trial including 26 patients with verified progressive breast cancer are presented. Seven patients discontinued treatment after only 2-3 vaccination weeks due to rapid disease progression or death. Nineteen patients were available for first evaluation after 6 vaccinations; 8/19 evaluable patients attained stable disease (SD) or minor regression while 11/19 patients had progressive disease (PD), indicating an effect of p53-specific immune therapy. This was supported by: (1) a positive correlation between p53 expression of tumor and observed SD, (2) therapy induced p53 specific T cells in 4/7 patients with SD but only in 2/9 patients with PD, and (3) significant response associated changes in serum YKL-40 and IL-6 levels identifying these biomarkers as possible candidates for monitoring of response in connection with DC based cancer immunotherapy. In conclusion, a significant fraction of breast cancer patients obtained SD during p53-targeting DC therapy. Data encourage initiation of a randomized trial in p53 positive patients evaluating the impact on progression free survival. PMID- 17285286 TI - Hemodynamic monitoring in shock and implications for management. International Consensus Conference, Paris, France, 27-28 April 2006. AB - OBJECTIVE: Shock is a severe syndrome resulting in multiple organ dysfunction and a high mortality rate. The goal of this consensus statement is to provide recommendations regarding the monitoring and management of the critically ill patient with shock. METHODS: An international consensus conference was held in April 2006 to develop recommendations for hemodynamic monitoring and implications for management of patients with shock. Evidence-based recommendations were developed, after conferring with experts and reviewing the pertinent literature, by a jury of 11 persons representing five critical care societies. DATA SYNTHESIS: A total of 17 recommendations were developed to provide guidance to intensive care physicians monitoring and caring for the patient with shock. Topics addressed were as follows: (1) What are the epidemiologic and pathophysiologic features of shock in the ICU? (2) Should we monitor preload and fluid responsiveness in shock? (3) How and when should we monitor stroke volume or cardiac output in shock? (4) What markers of the regional and micro circulation can be monitored, and how can cellular function be assessed in shock? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock? One of the most important recommendations was that hypotension is not required to define shock, and as a result, importance is assigned to the presence of inadequate tissue perfusion on physical examination. Given the current evidence, the only bio-marker recommended for diagnosis or staging of shock is blood lactate. The jury also recommended against the routine use of (1) the pulmonary artery catheter in shock and (2) static preload measurements used alone to predict fluid responsiveness. CONCLUSIONS: This consensus statement provides 17 different recommendations pertaining to the monitoring and caring of patients with shock. There were some important questions that could not be fully addressed using an evidence-based approach, and areas needing further research were identified. PMID- 17285290 TI - Interleukin 21 therapy increases the density of tumor infiltrating CD8+ T cells and inhibits the growth of syngeneic tumors. AB - Interleukin (IL)-21 is a recently discovered cytokine in early clinical development, which has shown anti-tumor activity in various animal models. In the present study, we examine the anti-tumor activity of IL-21 protein therapy in two syngeneic tumor models and its effect on the density of tumor infiltrating T cells. We treated mice bearing established subcutaneous B16 melanomas or RenCa renal cell carcinomas with intraperitoneal (i.p.) or subcutaneous (s.c.) IL-21 protein therapy and subsequently scored the densities of tumor infiltrating CD4(+) and CD8(+) T cells by immunohistochemistry. Whereas both routes of IL-21 administration significantly inhibited growth of small, established RenCa and B16 tumors, only s.c. therapy significantly inhibited the growth of large, established tumors. We found a greater bioavailability and significant drainage of IL-21 to regional lymph nodes following s.c. administration, which could account for the apparent increase in anti-tumor activity. Specific depletion of CD8(+) T cells with monoclonal antibodies completely abrogated the anti-tumor activity, whereas NK1.1(+) cell depletion did not affect tumor growth. In accordance, both routes of IL-21 administration significantly increased the density of tumor infiltrating CD8(+) T cells in both B16 and RenCa tumors; and in the RenCa model s.c. administration of IL-21 led to a significantly higher density of tumor infiltrating CD8(+) T cells compared to i.p. administration. The densities of CD4(+) T cells were unchanged following IL-21 treatments. Taken together, these data demonstrate that IL-21 protein has anti-tumor activity in established syngeneic tumors, and we show that IL-21 therapy markedly increases the density of tumor infiltrating CD8(+) T cells. PMID- 17285291 TI - Stochastic identification of bioreactor process exhibiting input multiplicity. AB - Bioreactor systems involve complex biochemical reactions, which make the systems highly non-linear in nature. Developing model based controllers for such processes require mathematical representations, which are simple, yet capable of capturing the non-linear process characteristics. Continuous bioreactor falls under the class of non-linear systems that exhibit input multiplicity in the optimal operating region, i.e., the operating region where identical outputs are obtained for multiple inputs. Linear modeling techniques are not useful for the referred class of systems for obvious reasons. Even for non-linear modeling techniques, the real bottleneck is to capture the bell-shaped parabolic structure of steady state characteristics exhibited by these systems. The stochastic approach of modeling, which is based on process input/output time-series data, is very useful for this purpose. The aim of this paper is to address the stochastic modeling issues related to bioreactor processes. In this work, three efficient modeling techniques have been studied, viz. block oriented NARMAX structure (Pearson and Pottmann in J Process Control 10:301-315, 2000), Bootstrap structure detection for NARMAX model (Kukreja et al. in Int J Control 77(2):132-143, 2004) and Wavelet-NARMAX model (Billings and Wei in Int J Syst Sci 36(3):137-152, 2005). PMID- 17285293 TI - Plasma exchange combined with immunosuppressive treatment in a child with rapidly progressive IgA nephropathy. AB - Although diffuse crescentic formation in immunoglobulin A (IgA) nephropathy, histologically characterized by extensive extracapillary proliferation, is assumed to have a poor prognosis, there has still been no established treatment because of the low prevalence of the condition, especially in pediatric patients. This paper reports on a 5-year-old boy with rapidly progressive IgA nephropathy requiring dialysis for 1 month. He had been treated with plasma exchange (PE) combined with immunosuppressive treatment, including steroids and mizoribine, because renal function deteriorated rapidly despite initial treatment with intravenous methylprednisolone pulse. The histological findings at that time revealed IgA nephropathy, with large circumferential cellular crescent formation in approximately 80% of the glomeruli. Three weeks after PE initiation, serum levels of creatinine and IgA-containing immune complexes returned to normal, and urinary protein excretion gradually decreased. The second renal biopsy taken 7 months later demonstrated mild IgA nephropathy with small fibrocellular crescents. This case report indicates that PE combined with immunosuppressive treatment may benefit children with rapidly progressive IgA nephropathy, even when extensive crescent formations are present. PMID- 17285294 TI - Etiology of nephrocalcinosis in northern Indian children. AB - This retrospective survey examines the etiology of nephrocalcinosis (NC) in 40 patients (26 boys), over an 8-year period. The median age at onset of symptoms and presentation was 36 months and 72 months, respectively. Clinical features included marked failure to thrive (82.5%), polyuria (60%) and bony deformities (52.5%). The etiology of NC included distal renal tubular acidosis (RTA) in 50% patients and idiopathic hypercalciuria and hyperoxaluria in 7.5% each. Other causes were Bartter syndrome, primary hypomagnesemia with hypercalciuria, severe hypothyroidism and vitamin D excess. No cause for NC was found in 12.5% patients. Specific therapy, where possible, ameliorated the biochemical aberrations, although the extent of NC remained unchanged. At a median (range) follow up of 35 (14-240) months, glomerular filtration rate (GFR) had declined from 82.0 (42-114) ml/min per 1.73 m2 body surface area to 70.8 (21.3-126.5) ml/min per 1.73 m2 body surface area (P = 0.001). Our findings confirm that, even with limited diagnostic facilities, protocol-based evaluation permits determination of the etiology of NC in most patients. PMID- 17285295 TI - The enigma of vascular cognitive disorder and vascular dementia. AB - The prevalence, morphology and pathogenesis of vascular dementia (VaD), recently termed vascular cognitive impairment, are a matter of discussion, and currently used clinical diagnostic criteria show moderate sensitivity (average 50%) and variable specificity (range 64-98%). In Western clinic-based series, VaD is suggested in 8-10% of cognitively impaired aged subjects. Its prevalence in autopsy series varies from 0.03 to 58%, with reasonable values of 8-15%, while in Japan it is seen in 22-35%. Neuropathologic changes associated with cognitive impairment include multifocal and/or diffuse disease and focal lesions: multi infarct encephalopathy, white matter lesions or arteriosclerotic subcortical (leuko)encephalopathy, multilacunar state, mixed cortico-subcortical type, borderline/watershed lesions, rare granular cortical atrophy, post-ischemic encephalopathy and hippocampal sclerosis. They result from systemic, cardiac and local large or small vessel disease. Recent data indicate that cognitive decline is commonly associated with widespread small ischemic/vascular lesions (microinfarcts, lacunes) throughout the brain with predominant involvement of subcortical and functionally important brain areas. Their pathogenesis is multifactorial, and their pathophysiology affects neuronal networks involved in cognition, memory, behavior and executive functioning. Vascular lesions often coexist with Alzheimer disease (AD) and other pathologies. Minor cerebrovascular lesions, except for severe amyloid angiopathy, appear not essential for cognitive decline in full-blown AD, while both mild Alzheimer pathology and small vessel disease may interact synergistically. The lesion pattern of "pure" VaD, related to arteriosclerosis and microangiopathies, differs from that in mixed-type dementia (AD with vascular encephalopathy), more often showing large infarcts, which suggests different pathogenesis of both types of lesions. Due to the high variability of cerebrovascular pathology and its causative factors, no validated neuropathologic criteria for VaD are available, and a large variability across laboratories still exists in the procedures for morphologic examination and histology techniques. PMID- 17285296 TI - Electrostatic control of the overall shape of calmodulin: numerical calculations. AB - The paper reports the results of numerical calculations of the pKa's of the ionizable groups and the electrostatic interactions between calmodulin lobes in three different states of calmodulin: calcium-free, peptide-free; calcium-loaded, peptide-free; and calcium-loaded, peptide-bound. NMR and X-ray studies revealed that in these states the overall structure of calmodulin adopts various conformations referred as: disordered semi-compact, extended and compact conformations, respectively. In addition, a new X-ray structure was recently reported (Structure, 2003, 11, 1303) showing that calcium-loaded, peptide-free calmodulin can also adopt a compact conformation in addition to the well known extended conformation. The calculated energy changes of calcium-loaded, peptide free calmodulin along the pathway connecting these two conformations provide a possible explanation for this structural plasticity. The effect of pH and organic compounds in the solution phase on the preference of calmodulin to adopt compact or extended conformations may be thus rationalized. Analysis of the contribution of the ionization changes to the energy of association of calmodulin lobes suggested that the formation of the compact forms requires protonation of several acidic residues. However, two different protonation scenarios are revealed: a protonation due to internal lobe organization and thus independent of the lobes association, and a protonation induced by the lobes association resulting to a proton uptake. In addition, the role of the individual residues on the energy of association of calmodulin lobes is calculated in two compact conformations (peptide-free and peptide-bound) and is shown that a set of residues always plays a dominant role in inter-domain interactions. PMID- 17285297 TI - Adenosine protects against suicidal erythrocyte death. AB - Suicidal death of erythrocytes or eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine exposure at the erythrocyte surface. The cell membrane scrambling is triggered by an increase in cytosolic Ca(2+) activity and activation of protein kinase C (PKC). Phosphatidylserine exposure fosters adherence of affected erythrocytes to the vascular wall. Thus, microcirculation in ischemic tissues may be impaired by the appearance of eryptotic erythrocytes. Ischemia leads to release of adenosine, which in most tissues leads to vasodilation and protects against cell injury. The present experiments explored whether adenosine influences mechanisms underlying eryptosis. Erythrocyte phosphatidylserine exposure was estimated from annexin V binding, cell volume from forward scatter and cytosolic Ca(2+) activity from Fluo3 fluorescence. Glucose depletion (for 24 or 48 h) significantly increased annexin binding and decreased forward scatter, effects partially reversed by adenosine. The protective effect of adenosine reached statistical significance (s.d.) at > =30 microM. Low Cl(-) solution (Cl(-) exchanged by gluconate for 24 h) similarly increased annexin binding and decreased forward scatter, effects again reversed by adenosine (s.d. at > or =10 and 30 microM, respectively). Similarly, phosphatase inhibitor okadaic acid (OA, 1 microM) and PKC activator phorbol 12-myristate-13-acetate (PMA, 3 microM) significantly enhanced annexin binding and decreased forward scatter. Adenosine significantly blunted the effects of OA and PMA on annexin V binding (s.d. at > or =30 and 10 microM, respectively) and the effect of OA on forward scatter (s.d. at > or =10 microM). In conclusion, adenosine inhibits eryptosis by a mechanism presumably effective downstream of PKC. The effect may participate in the maintenance of microcirculation in ischemic tissue. PMID- 17285298 TI - Tamoxifen treatment of myocardial infarcted female rats exacerbates scar formation. AB - Hormonal replacement therapy in postmenopausal women was associated with an increased incidence of nonfatal myocardial infarction. Selective estrogen receptor modulators were considered an alternative pharmacological approach. However, selective estrogen receptor modulators acting via estrogen receptor dependent and receptor-independent mechanisms may negatively influence cardiac remodeling. The present study tested the hypothesis that tamoxifen (TAM) treatment after coronary artery ligation compromised scar formation. TAM administration (10 mg kg(-1) day(-1) for 3 weeks) to postmyocardial infarcted (MI) female adult rats significantly increased scar surface area (TAM+MI = 0.67 +/- 0.08 vs MI = 0.45 +/- 0.06 cm(2)) and weight (TAM+MI = 0.071 +/- 0.007 vs MI = 0.050 +/- 0.006 grams). In the infarct region, a significant decrease (p < 0.05) of small calibre vessels (lumen diameter <50 microm) was observed in TAM treated post-MI rats (4.5 +/- 0.8 vessels/mm(2)), as compared to untreated MI rats (7 +/- 0.7 vessels/mm(2)). Consistent with the latter finding, 4-OH TAM caused a dose-dependent suppression of vascular endothelial growth factor (VEGF) stimulated (10(-9) mol/l) capillarity-like tubule formation by rat aortic endothelial cells in vitro via an estrogen receptor-independent mechanism. These data have demonstrated that TAM treatment of post-MI female rats exacerbated scar formation and may have occurred at least in part via the attenuation of new vessel formation in the infarct region. PMID- 17285299 TI - Hypoxia modulates gene expression of IP3 receptors in rodent cerebellum. AB - Hypoxic brain cell injury is a complex process that results from a series of intracellular events. In this work, we tested whether severe hypoxia for 6 h can affect gene expression and protein levels of intracellular calcium channels, ryanodine receptors, and inositol 1,4,5-trisphosphate receptors in mouse cerebellum. In addition, we tested the effect of hypoxia on cerebellar granular cells of rats. We have found that gene expression of types 1 and 2 IP(3) receptors is significantly increased after the exposure of mice to hypoxic stimulus for 6 h and also in rat cerebellar granular cells. Increased gene expression of IP(3) receptors was reflected in increased protein levels of these channels as well. In this process, reactive oxygen species are most probably involved, as antioxidant quercetin abolished hypoxia-induced increase in both types 1 and 2 IP3 receptor. Ryanodine receptors of types 1 and 2 and sarco(endo)plasmic reticulum Ca(2+)-ATPase were not affected by hypoxia on the level of messenger RNA. To test physiological consequences, we measured levels of intracellular calcium. We observed significantly elevated calcium level in hypoxic compared to normoxic cells. Deeper understanding of mechanisms, through which hypoxia regulates intracellular calcium, could point towards the development of new therapeutic approaches to reduce or suppress the pathological effects of cellular hypoxia, such as those seen in stroke or ischemia. PMID- 17285300 TI - Nitric oxide differentially regulates renal ATP-binding cassette transporters during endotoxemia. AB - Nitric oxide (NO) is an important regulator of renal transport processes. In the present study, we investigated the role of NO, produced by inducible NO synthase (iNOS), in the regulation of renal ATP-binding cassette (ABC) transporters in vivo during endotoxemia. Wistar-Hannover rats were injected with lipopolysaccharide (LPS(+)) alone or in combination with the iNOS inhibitor, aminoguanidine. Controls received detoxified LPS (LPS(-)). After LPS(+), proximal tubular damage and a reduction in renal function were observed. Furthermore, iNOS mRNA and protein, and the amount of NO metabolites in plasma and urine, increased compared to the LPS(-) group. Coadministration with aminoguanidine resulted in an attenuation of iNOS induction and reduction of renal damage. Gene expression of 20 ABC transporters was determined. After LPS(+), a clear up-regulation in Abca1, Abcb1/P-glycoprotein (P-gp), Abcb11/bile salt export pump (Bsep), and Abcc2/multidrug resistance protein (Mrp2) was found, whereas Abcc8 was down regulated. Up-regulation of Abcc2/Mrp2 was accompanied by enhanced calcein excretion. Aminoguanidine attenuated the effects on transporter expression. Our data indicate that NO, produced locally by renal iNOS, regulates the expression of ABC transporters in vivo. Furthermore, we showed, for the first time, expression and subcellular localization of Abcb11/Bsep in rat kidney. PMID- 17285301 TI - Is the vascular endothelium under the control of aldosterone? Facts and hypothesis. AB - Fluid and electrolyte balance in the human organism is controlled by aldosterone, a mineralocorticoid hormone of the suprarenal glands. The major target cells are localized in the kidney where the hormone controls transepithelial salt transport. Over the past few years, evidence has been accumulated that cells of the cardiovascular system are also targeted by the hormone. As an example, endothelial cells resemble similar mechanisms triggered by aldosterone as shown for the kidney. Although the pathological alterations induced by aldosterone excess are obvious, the physiological changes are largely unknown. On the basis of recent experiments, using atomic force microscopy as an imaging tool and a mechanical sensor, I present a hypothesis on the physiological role of aldosterone in endothelial function and its potential implications in the control of blood pressure. PMID- 17285304 TI - Extraction across supported liquid membranes by use of electrical fields. PMID- 17285302 TI - Regulation of membrane excitability by intracellular pH (pHi) changers through Ca2+-activated K+ current (BK channel) in single smooth muscle cells from rabbit basilar artery. AB - Employing microfluorometric system and patch clamp technique in rabbit basilar arterial myocytes, regulation mechanisms of vascular excitability were investigated by applying intracellular pH (pH(i)) changers such as sodium acetate (SA) and NH(4)Cl. Applications of caffeine produced transient phasic contractions in a reversible manner. These caffeine-induced contractions were significantly enhanced by SA and suppressed by NH(4)Cl. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was monitored in a single isolated myocyte and based the ratio of fluorescence using Fura-2 AM (R (340/380)). SA (20 mM) increased and NH(4)Cl (20 mM) decreased R (340/380) by 0.2 +/- 0.03 and 0.1 +/- 0.02, respectively, in a reversible manner. Caffeine (10 mM) transiently increased R (340/380) by 0.9 +/- 0.07, and the ratio increment was significantly enhanced by SA and suppressed by NH(4)Cl, implying that SA and NH(4)Cl may affect [Ca(2+)](i) (p < 0.05). Accordingly, we studied the effects of SA and NH(4)Cl on Ca(2+)-activated K(+) current (IK(Ca)) under patch clamp technique. Caffeine produced transient outward current at holding potential (V (h)) of 0 mV, caffeine induced transient outward K(+) current, and the spontaneous transient outward currents were significantly enhanced by SA and suppressed by NH(4)Cl. In addition, IK(Ca) was significantly increased by acidotic condition when pH(i) was lowered by altering the NH(4)Cl gradient across the cell membrane. Finally, the effects of SA and NH(4)Cl on the membrane excitability and basal tension were studied: Under current clamp mode, resting membrane potential (RMP) was -28 +/- 2.3 mV in a single cell level and was depolarized by 13 +/- 2.4 mV with 2 mM tetraethylammonium (TEA). SA hyperpolarized and NH(4)Cl depolarized RMP by 10 +/- 1.9 and 16 +/- 4.7 mV, respectively. SA-induced hyperpolarization and relaxation of basal tension was significantly inhibited by TEA. These results suggest that SA and NH(4)Cl might regulate vascular tone by altering membrane excitability through modulation of [Ca(2+)](i) and Ca(2+)-activated K channels in rabbit basilar artery. PMID- 17285305 TI - Evaluation of amplified cRNA targets for oligonucleotide microarrays. AB - Due to their hybridization specificity and capacity for systematic gene discovery, oligonucleotide-based microarray platforms offer numerous advantages over the cDNA microarrays currently widely used for comprehensive analysis of gene expression. Although fluorescently labeled amplified cRNA generated by T7 transcription is generally used in oligonucleotide microarrays, the feasibility of this combination (and that of cDNA microarrays) is yet to be studied systematically. In this paper, we performed a comparative study using a direct labeling method and T7 amplification to evaluate amplified cRNA targets for oligonucleotide microarrays. The efficiency of incorporation of Cy3- and Cy5-CTP into the target preparations, the reproducibility and the number of genes detected were investigated for each labeling approach and compared. The 12 genes that showed different expression profiles in the two labeling methods were evaluated by quantitative real-time PCR. In the 60-mer oligonucleotide microarray, amplified cRNA targets prepared by the T7 amplification method showed higher reproducibility and reliability than targets prepared by the direct labeling method in a comparative analysis of gene expression. This result also suggests the importance of fragmenting cRNA down to lengths of 50-200 bases before the hybridization process. PMID- 17285306 TI - Position of the reduced mycorrhizal colonisation (Rmc) locus on the tomato genome map. AB - Our research aims to investigate the molecular communication between land plants and arbuscular mycorrhizal (AM) fungi in the establishment of symbiosis. We have identified a mutation in the facultative AM host tomato, which we named rmc. Plants that are homozygous for rmc no longer host most AM fungi. The mutation also affects the interaction of tomato with root knot nematode and Fusarium wilt. However, the function/s encoded by the intact Rmc locus is/are unknown. To clone and sequence the gene or genes that comprise the Rmc locus, we have initiated a positional cloning project. In this paper, we report the construction of mapping populations and use of molecular markers from the published genome map to identify the location of Rmc on tomato chromosome 8. Nucleotide binding site leucine rich repeat resistance genes, reported to reside in the same region of that chromosome, provided insufficient differences to develop cleaved amplified polymorphic sequence markers. Therefore, we were unable to map these sequences in relation to rmc. Our results potentiate future work to identify the Rmc function and to determine the genetic basis for the multiple plant-microbe interaction functions that the rmc mutation has defined. PMID- 17285303 TI - Touch sensitivity in Caenorhabditis elegans. AB - The nematode Caenorhabditis elegans was the first organism for which touch insensitive mutants were obtained. The study of the genes defective in these mutants has led to the identification of components of a mechanosensory complex needed for specific cells to sense gentle touch to the body. Multiple approaches using genetics, cell biology, biochemistry, and electrophysiology have characterized a channel complex, containing two DEG/ENaC pore-forming subunits and several other proteins, that transduces the touch response. Other mechanical responses, sensed by other cells using a variety of other components, are less well understood in C. elegans. Many of these other senses may use TRP channels, although DEG/ENaC channels have also been implicated. PMID- 17285307 TI - [Furunculoid skin lesions after travel to the tropics]. AB - We present a case of cutaneous myiasis (Tumbu fly; Cordylobia anthropophaga) in a German traveller returning from Africa. Myiasis is caused by dipterous larvae invading human or animal tissues. The diagnosis is based on the travel history and specific features of the furunculoid skin lesions. Larvae are extracted with forceps or are surgically removed. PMID- 17285308 TI - Drosophila retinophilin contains MORN repeats and is conserved in humans. AB - The function of conserved novel human genes can be efficiently addressed in genetic model organisms. From a collection of genes expressed in the Drosophila visual system, cDNAs expressed in vertebrates were identified and one similar to a novel human gene was chosen for further investigation. The results reported here characterize the Drosophila retinophilin gene and demonstrate that a similar gene is expressed in the human retina. The Drosophila and human retinophilin sequences are 50% identical, and they share an additional 16% conserved substitutions. Examination of the cDNA and genomic sequence indicates that it corresponds to the gene CG10233 of the annotated genome and predicts a 22.7 kDa protein. Polyclonal antibodies generated to a predicted retinophilin peptide recognize an antigen in Drosophila photoreceptor cells. The retinophilins encode 4 copies of a repeat associated with a Membrane Occupation and Recognition Nexus (MORN) function first discovered in junctophilins, which may interact with the plasma membrane. These results therefore show that Drosophila retinophilin is expressed in fly photoreceptor cells, demonstrate that a conserved human gene is expressed in human retina, and suggest that a mutational analysis of the Drosophila gene would be valuable. PMID- 17285310 TI - TRP channels as target sites for insecticides: physiology, pharmacology and toxicology. AB - Transient receptor potential (TRP) channels are attracting attention from various research areas including physiology, pharmacology and toxicology. Our group has focused on TRPA1 channels and revealed their expression pattern, ion channel kinetics and pharmacological characteristics. From Integrated Pest Management point of view, TRP channels could be a possible new target site of pest control agents as well as the primary or secondary target site for known insecticides. We have examined expressed TRPA1 channels using physiological and pharmacological methods to clarify the function of these channels. Here, we show that the TRPA1 is activated by the insecticide and natural toxin allyl isothiocyanate which is known as insecticide. PMID- 17285309 TI - The CBF gene family in hexaploid wheat and its relationship to the phylogenetic complexity of cereal CBFs. AB - Most temperate plants tolerate both chilling and freezing temperatures whereas many species from tropical regions suffer chilling injury when exposed to temperatures slightly above freezing. Cold acclimation induces the expression of cold-regulated genes needed to protect plants against freezing stress. This induction is mediated, in part, by the CBF transcription factor family. To understand the evolution and function of this family in cereals, we identified and characterized 15 different CBF genes from hexaploid wheat. Our analyses reveal that wheat species, T. aestivum and T. monococcum, may contain up to 25 different CBF genes, and that Poaceae CBFs can be classified into 10 groups that share a common phylogenetic origin and similar structural characteristics. Six of these groups (IIIc, IIId, IVa, IVb, IVc and IVd) are found only in the Pooideae suggesting they represent the CBF response machinery that evolved recently during colonization of temperate habitats. Expression studies reveal that five of the Pooideae-specific groups display higher constitutive and low temperature inducible expression in the winter cultivar, and a diurnal regulation pattern during growth at warm temperature. The higher constitutive and inducible expression within these CBF groups is an inherited trait that may play a predominant role in the superior low temperature tolerance capacity of winter cultivars and possibly be a basis of genetic variability in freezing tolerance within the Pooideae subfamily. PMID- 17285311 TI - Gene expression profiling in lung tissues from rats exposed to formaldehyde. AB - Formaldehyde is a ubiquitous toxic organic compound recently classified as a carcinogen by the International Agency for Research on Cancer and one of the major factors causing sick building syndrome. In this study, we have investigated the effects of formaldehyde on mRNA expression in rat lung tissues by applying genomics. Rats were exposed to ambient air and two different concentrations of formaldehyde (0, 5, 10 ppm) for 2 weeks at 6 h/day and 5 days/week in an inhalation chamber. Malondialdehyde (MDA) assay and carbonyl spectrometric assay were conducted to determine lipid peroxidation and protein oxidation levels and Comet assays were used for genotoxicity evaluation. Level of MDA, carbonyl insertion and DNA damage in the lungs of rats exposed to FA were found to be dose dependently increased. Gene expression was evaluated by using a bio-array hybridization analysis. A total of 21 (2 up- and 19 down-regulated) genes were identified as biomarkers for formaldehyde effects. Several differentiated gene groups were found. Genes involved in apoptosis, immunity, metabolism, signal transduction, transportation, coagulation and oncogenesis were found to be up- and down-regulated. Among these genes, the mRNA expressions of cytochrome P450, hydroxymethylbilane synthase, glutathione reductase, carbonic anhydrase 2, natriuretic peptide receptor 3, lysosomal associated protein transmembrane 5, regulator of G-protein signaling 3, olfactomedin related ER localized protein, and poly (ADP-ribose) polymerase-1 were confirmed by quantitative RT-PCR analysis. In summary, the MDA lipid peroxidation and the carbonyl protein oxidation assays showed that cytotoxic effects increased with increasing formaldehyde levels. Genomic analysis showed that 21 genes were up- or down regulated. Of these genes, nine were confirmed by quantitative RT-PCR and could be potential biomarkers for human diseases associated with formaldehyde exposure. PMID- 17285312 TI - Activation of mitogen activated protein kinase (MAPK) during carbon tetrachloride intoxication in the rat liver. AB - Carbon tetrachloride (CCl(4): 4 ml/kg body weight as a 1:1 mixture of CCl(4) and mineral oil) was orally administered to rats. After 12 h the activity of plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) was significantly higher than that of the control group and plasma AST and ALT activities increased thereafter. These results indicated that the necrotic process was active at about 12 h and developed thereafter. After 2-24 h of CCl(4) administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced as early as 2 h after CCl(4) intoxication and thereafter. Phosphorylated JNK (c-Jun NH(2)-terminal kinase) and phospho-ERK1/2 (extracellular signal-regulated kinase1/2) were significantly increased transiently 1-3 h after treatment with CCl(4), while phosphorylated p38 decreased significantly 1-24 h after CCl(4) treatment. These results indicated that the change in MAPKs (mitogen activated protein kinases) slightly preceded that in vitamin C, the most sensitive chemical indicator of oxidative stress. PMID- 17285313 TI - Acute, nonfatal intoxication with trichloroethylene. AB - Nonfatal acute inhalation of trichloroethylene (TRI) at work was described. The subject, male, 54 years old, was drawn unconscious by a metal-degreasing machine and immediately sheltered in intensive care unit. Other than basic life support and common laboratory indices, blood and urine were collected to measure dose and kidney effect parameters such as TRI in blood and urine, trichloroethanol (TCE) and trichloroacetic acid (TCA) in urine, and total urinary proteins (TUP), urinary glutamine synthetase (GS) and urinary N-acetyl-beta-D-glucosaminidase (NAG). Two hours after accident, TRI in blood was 9 mg/l, but after 38 h it was below 1 mg/l. TCE and TCA have a peak 11 and 62 h after poisoning, respectively. Acute renal involvement was revealed by a peak of urinary proteins and enzymes 7 h after exposure with a second peak 74 h after. Seven day after hospitalisation the patient was dismissed with complete recovery. This nonfatal intoxication with TRI shows that the exposure was approximately 150 ppm, three times the ACGIH TLV (50 ppm) and that kidney was the only organ affected. Urinary enzymes, in particular GS, are good indices to monitor transient effects of TRI on the kidney. PMID- 17285314 TI - Preclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent. AB - BACKGROUND: Noscapine, a naturally occurring antitussive phthalideisoquinoline alkaloid, is a tubulin-binding agent currently in Phase I/II clinical trials for anticancer therapy. Unlike currently available antimitotics such as taxanes and vincas, noscapine is water-soluble, well tolerated, and shows no detectable toxicity. OBJECTIVE: The goal was to develop a simple, sensitive, quantitative, selective, and less time-consuming high-performance liquid chromatography (HPLC) method for determination of noscapine and to study its pharmacokinetics in mice models. METHOD: Noscapine was extracted from mice plasma using the protein precipitation method and detected using a reversed-phase C8 column with mobile phase consisting of 35% acetonitrile and 65% ammonium acetate buffer (pH 4.5) at 232 nm wavelength. Pharmacokinetic studies of noscapine were performed in mice following intravenous bolus at 10 mg/kg and oral administrations at 75, 150, and 300 mg/kg. RESULTS: The standard curves for noscapine estimation were linear between 390 and 50,000 ng/ml (lower limit of quantification was 390 ng/ml) and the recovery was approximately 80%. Following 10 mg/kg intravenous dose, mean plasma concentrations of 7.88 microg/ml were achieved at 5 min in mice and declined with undetectable levels at 4 h. The mean total body clearance was 4.78 l/h. The mean volume of distribution (V (d)) was 5.05 l. Non-compartmental analysis yielded the mean area under the plasma concentration-time curve (AUC) for noscapine as 53.42, 64.08, and 198.35 h microg/ml reaching maximum plasma concentrations (C (max)) of 12.74, 23.24, and 46.73 microg/ml at a t (max) of 1.12, 1.50, and 0.46 h at the linearly increasing dose levels. CONCLUSION: A rapid and simple HPLC/UV method for the quantification of noscapine in plasma has been developed to study pharmacokinetics of noscapine at tumor-suppressive doses in the mouse. Since orally available anticancer drugs are rare, therefore, noscapine, an innocuous agent, having a mean oral bioavailability of 31.5% over the studied dose range merits its further advancement in humans for anticancer therapy. PMID- 17285315 TI - Population pharmacokinetics of a HER2 tyrosine kinase inhibitor CP-724,714 in patients with advanced malignant HER2 positive solid tumors. AB - PURPOSE: To develop a population pharmacokinetic (popPK) model for CP-724,714, a novel HER2 tyrosine kinase inhibitor is under development for the treatment of advanced HER2 positive cancers. METHODS: Concentration-time data (n = 484) from 30 cancer patients receiving daily oral CP-724,714 at doses of 250 mg QD, 250 mg BID, 250 mg TID, and 400 mg BID in 21-day cycles in an open label First-in-Human dose-escalation study were evaluated. Serum concentrations of CP-724,714 were obtained after single dose and at steady state. Nonlinear mixed effect analysis in NONMEM using first order conditional estimation with interaction (FOCEI) was performed. The effect of covariates was assessed. Diagnostic plots, decrease of objective function value (>7.8), bootstrapping, and predictive check were used as model selection criteria. RESULTS: A 2-compartment first-order absorption pharmacokinetic (PK) model with inter-subject variability (ISV) on the apparent oral elimination clearance (CL/F), apparent central volume of distribution (V1/F), apparent peripheral volume of distribution (V2/F), and first-order oral absorption rate constant (ka), interoccasion variability (IOV) on CL/F, and body weight (WT) as covariate on CL/F was developed. There was no evidence of dose dependent and/or time-dependent PK. CL/F increased with increasing WT. The ISV of CL/F was reduced by approximately 20% with WT as a covariate. Age, race, and liver metastasis did not influence CP-724,714 disposition. CONCLUSIONS: A popPK model was developed that adequately described the pharmacokinetics of CP-724,714. WT was identified as a covariate on CL/F that reduced ISV and improved model performance. Future studies will further assess the importance of WT as a pharmacokinetic covariate. The proposed popPK model can be used to simulate CP 724,714 Phase 2/3 trials. PMID- 17285316 TI - Tissue distribution and depletion kinetics of bortezomib and bortezomib-related radioactivity in male rats after single and repeated intravenous injection of 14 C-bortezomib. AB - PURPOSE: The body distribution of total radioactivity (TR) and bortezomib was investigated in male Sprague-Dawley rats after single and repeated i.v. (bolus) administration with (14)C-labelled bortezomib (VELCADE) (0.2 mg/kg; 0.28 MBq./kg). METHODS: Bortezomib was dosed on days 1, 4, 8, and 11 (i.e. a clinical dosing cycle) and the animals were sacrificed at selected time points following single and repeated dose administration for the quantification of TR in blood, plasma, and various tissues by liquid scintillation counting following organ dissection or by quantitative whole body autoradiography. In selected tissues, bortezomib levels were determined by LC-MS/MS. RESULTS: In general, plasma TR levels were less than 10% of the corresponding blood concentrations. TR was rapidly and widely distributed to the tissues with only limited penetration into the central nervous system (CNS). In the tissues, highest levels of TR were measured in bortezomib-eliminating organs (liver and kidney), lymphoid tissues, and regions of rapidly dividing cells (e.g. the bone marrow, intestinal mucosa). Low TR concentrations were found in the CNS (tissue-to-blood ratio of approximately 0.05 after repeated dosing). With the exception of the liver, TR consisted almost exclusively of the parent drug. Tissue concentrations of TR and bortezomib increased up to about threefold from the first to the third dose administration, after which they remained constant. CONCLUSION: No undue tissue accumulation of TR and of bortezomib was observed in rats following a full clinical dosing cycle of bortezomib. PMID- 17285317 TI - Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. AB - PURPOSE: Albumin-bound paclitaxel, ABI-007 (Abraxane((R))), has a different toxicity profile than solvent-based paclitaxel, including a lower rate of severe neutropenia. The combination of ABI-007 and carboplatin may have significant activity in a variety of tumor types including non-small and small cell lung cancer, ovarian cancer, and breast cancer. The purpose of this study was to determine the maximum tolerated dose (MTD) of ABI-007, on three different schedules in combination with carboplatin. METHODS: Forty-one patients with solid tumors were enrolled, and received ABI-007 in combination with carboplatin AUC of 6 on day 1. Group A received ABI-007 at doses ranging from 220 to 340 mg/m(2) on day 1 every 21 days; group B received ABI-007 at 100 or 125 mg/m(2) on days 1, 8, and 15 every 28 days; and group C received ABI-007 125 or 150 mg/m(2) on days 1 and 8 every 21 days. Dose-limiting toxicities were assessed after the first cycle. Doses were escalated in cohorts of three to six patients. Fifteen patients participated in a pharmacokinetic study investigating the effects of the sequence of infusion. ABI-007 was infused first followed by carboplatin in cycle 1, and vice versa in cycle 2. RESULTS: The MTD of ABI-007 in combination with carboplatin was 300, 100, and 125 mg/m(2) in groups A, B, and C, respectively. Myelosuppression was the primary dose limiting toxicity. No unexpected or new toxicities were reported. Sequence of infusion did not affect either the pharmacokinetics of ABI-007 or the degree of neutropenia. Responses were seen in melanoma, lung, bladder, esophageal, pancreatic, breast cancer, and cancer of unknown primary. CONCLUSIONS: The recommended dose for phase II studies of ABI 007 in combination with carboplatin (AUC of 6) is 300, 100, 125 mg/m(2) for the schedules A, B, and C, respectively. The combination of ABI-007 and carboplatin is well tolerated and active in this heavily pretreated patient population. PMID- 17285318 TI - Physical activity and mental well-being in older people participating in the Better Ageing Project. AB - Increasing evidence suggests that physical activity can prevent some aspects of mental illness in older people such as depression, dementia and Alzheimer's disease. Additionally, limited research has shown that engagement in structured exercise can improve aspects of psychological well-being such as mood and self perceptions in older adults. However, the relationship between incidental daily activity such as walking or time spent sedentary, with psychological well-being has not been investigated. The Better Ageing Project provided an opportunity to assess well-being and quality of life using standardised questionnaires with 176 adults aged 70 and over. Accelerometry was used to objectively assess daily energy expended in physical activity at different levels of intensity. In addition, an assessment of the impact of the 12-month Better Ageing structured group exercise programme was assessed through questionnaires and interviews. Total daily physical activity energy expenditure (joules/day) and amount of time spent in activity of at least moderate intensity were weakly related (r = 0.20 0.28) to quality of life, subjective well-being and physical self-perceptions. Time spent sedentary (min/day) was weakly and negatively related to several mental health indicators. The quantitative data showed only minor psychological benefits of the exercise intervention. In contrast, interviews with 27 research participants and 4 exercise leaders suggested that important improvements in perceived function and social benefits had been experienced. PMID- 17285319 TI - Gastropod grazers and nutrients, but not light, interact in determining periphytic algal diversity. AB - The potential interactions of grazing, nutrients and light in influencing autotroph species diversity have not previously been considered. Earlier studies have shown that grazing and nutrients interact in determining autotroph species diversity, since grazing decreases species diversity when nutrients (i.e. N or P) limit autotroph growth, but increases it when nutrients are replete. We hypothesized that increased light intensities would intensify the interactions between grazing and nutrients on algal species diversity, resulting in even stronger reductions in algal species diversity through grazing under nutrient poor conditions, and to even stronger increases of algal species diversity through grazing under nutrient-rich conditions. We studied the effects of grazing (absent, present), nutrients (ambient, N + P enriched) and light (low light, high light) on benthic algal diversity and periphyton C:nutrient ratios (which can indicate algal nutrient limitation) in a factorial laboratory experiment, using the gastropod grazer Viviparus viviparus. Grazing decreased algal biomass and algal diversity, but increased C:P and N:P ratios of periphyton. Grazing also affected periphyton species composition, by decreasing the proportion of Spirogyra sp. and increasing the proportion of species in the Chaetophorales. Grazing effects on diversity as well as on periphyton N:P ratios were weakened when nutrients were added (interaction between grazing and nutrients). Chlorophyll a (Chl a) per area increased with nutrient addition and decreased with high light intensities. Light did not increase the strength of the interaction between grazing and nutrients on periphytic algal diversity. This study shows that nutrient addition substantially reduced the negative effects of grazing on periphytic algal diversity, whereas light did not interact with grazing or nutrient enrichment in determining periphytic algal diversity. PMID- 17285320 TI - [Training methods for regional anaesthesia. Evaluation and comparison]. AB - INTRODUCTION: Optimized training facilities are the key to efficient teaching of regional anesthesia. MATERIAL AND METHODS: A combination of Thiel's embalming method, flap dissection and pulse simulation was offered to participants in several workshops on regional anesthesia. Tutors, experienced anesthetists and anatomists, evaluated the workshop and compared Thiel's method to classic formaldehyde conservation. Additionally both embalming methods were assessed with regard to the mechanical properties according to the requirements of regional anesthesia. RESULTS: The evaluation showed high acceptance of the method offered in the workshop. In a comparison of fixation methods Thiel's method was generally preferred as it presented more similar conditions to living patients and almost ideal conditions for regional anesthesia. CONCLUSION: The presented method is an optimized, strongly accepted teaching and training tool for teaching regional anesthesia. PMID- 17285321 TI - Guidelines for doctors attending detainees in police custody: a consensus conference in France. AB - Medical practice in police custody needs to be harmonized. A consensus conference was held on 2-3 December 2004 in Paris, France. The health, integrity, and dignity of detainees must be safeguarded. The examination should take place in the police station so that the doctor can assess the conditions in which the detainee is being held. If the minimum conditions needed for a medical examination are not available, the doctor may refuse to express an opinion as to whether the detainee is fit to be held in custody or may ask for the detainee to be examined in a hospital. Doctors are subject to a duty of care and prevention. They should prescribe any ongoing treatment that needs to be continued, as well as any emergency treatment required. Custody officers may monitor the detainee and administer medication. However, their role should not be expected to exceed that required of the detainee's family under normal circumstances and must be specified in writing on the medical certificate. Doctor's opinion should be given in a national standard document. If the doctors consider that the custody conditions are disgraceful, they may refuse to express an opinion as to whether the detainee is fit for custody. PMID- 17285322 TI - Nicotine and cotinine in infants dying from sudden infant death syndrome. AB - The aim of this component of the German Study on Sudden Infant Death was to determine (1) nicotine concentrations in hair (NCH), as a marker of long standing exposure to tobacco, (2) cotinine concentrations in pericardial fluid (CCP) and (3) cotinine concentrations in liquor cerebrospinalis (CCL), the latter measures being markers of recent exposure to tobacco in the last few hours of life. The results obtained were compared with data on parental smoking revealed from interviews. In 100 cases of sudden infant death syndrome, material was taken at autopsy to determine NCH. In 41 cases, NCH and CCP, and in 70 cases, NCH and CCL were determined. Infants of mothers who stated having smoked during pregnancy had higher NCH than infants of non-smoking mothers (p = 0.008). Furthermore, there was a weak but statistically significant relationship between NCH's and the daily cigarette consumption of the mother during pregnancy (n = 64, r = 0.24, p = 0.05). In 43% of infants, nicotine could be detected in their hair, although the mothers had said at the interview that they did not smoke during pregnancy. On the other hand, in 33% of infants whose mother stated they had smoked during pregnancy nicotine was not detectable in the infant's hair. CCP's were strongly correlated with CCL's (r = 0.62, p = 0.0027). For this reason, both parameters were treated as equivalent for the detection of tobacco smoke exposure in the last hours before death. The influence of breast-feeding was evaluated by comparison of the nicotine concentrations in breast fed and non-breast-fed infants from smokers and non-smokers. Fivefold higher nicotine concentrations were determined in non-breast-fed infants of parents who smoked as compared to all other groups. It can be concluded that nicotine intake by passive smoking is much more important than by breast-feeding. We conclude that both interview data and biochemical measures should be sought to understand the true exposure to tobacco smoke. PMID- 17285323 TI - [Genetic bases of Hirschsprung's disease]. AB - Hirschsprung's disease constitutes a neural crest stem cell disorder (neurocristopathy) which is caused by absent or malfunctional intestinal intramural ganglion cells. The rostral extension of the aganglionic segment is variable. Hirschsprung's disease can be classified into type 1 (short segment) and type 2 (long segment) forms. It is limited to the gastrointestinal tract, but may occur in the syndromal context of manifold genetic diseases in 12% of patients. The prevalence is 1:5,000 with a distinct male predominance of 4-5:1. Numerous genes and non-coding polymorphous DNA sequence variants are involved in the pathogenesis of Hirschsprung's disease. The most important gene is RET. Susceptibility loci on 3p21, 9q31 and 19q12 interact with this gene. Downstream of RET, two new genes, GALNACT-2 and RASGEF1A, have also been identified. A recently described, frequent, non-coding RET variant, RET+3, is significantly associated with susceptibility to Hirschsprung's disease and carries a 20-fold increased risk of contracting the disease compared to rarer alleles. PMID- 17285324 TI - Intestinal-type adenocarcinoma arising in a congenital sublingual teratoid cyst. PMID- 17285325 TI - Search for residual prostate cancer on pT0 radical prostatectomy after positive biopsy. AB - Reported incidence of no residual prostate cancer (i.e. pathological stage pT0) on radical prostatectomy ranges from 0.07 to 4.2%. The incidence is higher after neoadjuvant endocrine treatment. The aim of this study was to search for residual cancer on radical prostatectomy (RP) specimens when an initial sampling failed to find the cancer in patients with positive biopsy. Our database of 1,328 consecutive patients whose biopsies and RP specimen were both examined at the Polytechnic University-United Hospitals of the Marche Region between March 1995 and June 2006 was reviewed. The radical prostatectomies were grossly completely sampled and examined with the whole mount technique. We identified eight patients (i.e. 0.6%; three untreated and five hormonally treated preoperatively, i.e. 0.3 and 0.8%, respectively, of the total number of RPs included in the study) with positive biopsy and with no residual cancer in the initial routine histological examination of the RP. The RP of this group of eight was subjected to additional sectioning and evaluation of the paraffin blocks of the prostatectomy, also after block-flipping, immunostaining with an antibody against CAM 5.2, p63, PSA, and alpha-methylacyl-CoA racemase, and DNA specimen identity analysis. There were no cases with a false positive biopsy diagnosis, and cancer was not overlooked or missed in the initial routine histological examination of any of the 8 pT0 RPs. A minute focus of cancer (the diameter was always below 2.0 mm) was found on the additional sections in five. In particular, cancer was found after block-flipping in one of them. In an additional case, cancer was eventually discovered after immunostaining tissue sections for cytokeratin CAM 5.2, for p63 and PSA. In the remaining two cases (one untreated and the other hormonally treated), cancer was not found (0.15% of the 1,328 RPs included in the study); the review of the description of the macroscopic appearance of the RP and of its slides revealed that part of the peripheral zone corresponding to the site of the positive biopsy was missing, i.e. not removed from the patient at the time of the operation at least in one of the two. DNA specimen analysis confirmed the identity of the biopsy and prostatectomy in both. An extensive search for residual cancer reduces the number of pT0 RPs after a positive biopsy from 0.6 to 0.15%. It is recommended to have the needle biopsy reviewed, carefully look again at the radical prostatectomy, do deeper sections and then flip certain paraffin blocks. In addition, atypical foci should be stained for basal cell markers and often AMACR, especially in hormone-treated cases. If a block is missing part of the peripheral zone (capsular incision), this should be commented on. DNA analysis for tissue identity should be performed when the other steps have been taken without finding cancer. PMID- 17285326 TI - Membrane cholesterol is required for activity of Vibrio vulnificus cytolysin. AB - Vibrio vulnificus cytolysin (VVC) forms a pore in the plasma membrane and induces cytolysis of various cells including erythrocytes, neutrophil and endothelial cells. The cytolytic activity of VVC is inhibited by exogenously added cholesterol, suggesting that membrane cholesterol might be required for VVC cytolytic activity. However, there is no direct evidence that membrane cholesterol is involved in VVC-induced cytolysis. Herein we demonstrate that membrane cholesterol is required for binding of VVC to the plasma membrane. Membrane cholesterol depletion with methyl-beta-cyclodextrin inhibited VVC induced K(+) release, 2-deoxy glucose release and Ca(2+) influx, which are indicators of VVC pore formation. The cholesterol depletion-induced blockage of VVC cytolysis was due to the inhibition of VVC binding to membrane. These findings suggest that interaction with cholesterol is required for activity of VVC. PMID- 17285327 TI - Differential distribution of adenosine receptors in rat cochlea. AB - Adenosine is a constitutive cell metabolite that can be released from cells via specific bi-directional transporters and is an end-point for nucleotide hydrolysis. In the extracellular space, adenosine becomes a signalling molecule for P1 (adenosine) receptors that modulate physiological responses in a wide range of mammalian tissues. Whereas adenosine signalling has been implicated in the regulation of cochlear blood flow and in cochlear protection from oxidative damage, the potential roles for adenosine signalling in the modulation of sound transduction and auditory neurotransmission have not been established. We have characterised the expression and distribution of adenosine receptors in the rat cochlea. mRNA transcripts for all four subtypes of adenosine receptors (A(1), A(2A), A(2B) and A(3)) were detected in dissected cochlear tissue by using reverse transcription/polymerase chain reaction analysis. The protein distribution for the A(1), A(2A) and A(3) receptor subtypes was identified by immunoperoxidase histochemistry and confocal immunofluorescence labelling. These receptors were differentially expressed in the organ of Corti, spiral ganglion neurones, lateral wall tissues and cochlear blood vessels. The distribution of adenosine receptors in sensory and neural tissues and in the vasculature coincided with other elements of purinergic signalling (P2X and P2Y receptors, ectonucleotidases), consistent with the integrative regulation of many physiological processes in the cochlea by extracellular nucleotides and nucleosides. Our study provides a framework for further investigation of adenosine signalling in the inner ear, including putative roles in oxidative stress responses. PMID- 17285329 TI - Unusual presentation of ulnar artery aneurysm and dissection with associated anomalous radial artery: appearances on multi-detector row CT angiography. AB - We present a case of ulnar artery aneurysm and dissection associated with a congenitally hypoplastic ipsilateral radial artery. We postulate that the aetiology is due to increased blood flow through the ulnar artery as a consequence of the radial artery anomaly, therefore making the ulnar artery more vulnerable to aneurysm formation and traumatic damage. This might represent a variant of the hypothenar hammer syndrome with associated ulnar artery dissection and recurrent distal embolisation manifesting as Raynaud's phenomenon. Forearm arterial injuries, treatment and the importance of upper limb arterial anatomical variations are also discussed. To our knowledge, this is the first reported case of its type diagnosed by multi-detector row computed tomography angiography. PMID- 17285328 TI - Expression of the Oct-2 transcription factor in mouse mammary gland and cloning and characterization of a novel Oct-2 isoform. AB - Oct-2 is a member of the POU family of transcription factors, which specifically bind to the octamer DNA motif ATGCAAAT and its closely related sequences. Unlike its ubiquitous counterpart Oct-1, Oct-2 is thought to be expressed only in B lymphocytes and neuronal cells and is mainly involved in immunoglobulin gene expression. We show here that Oct-2 is also expressed in the epithelial cells of mouse mammary gland, and that this expression is developmentally regulated. Rapid amplification of cDNA ends and subsequent cDNA cloning indicate that the mammary gland expresses multiple Oct-2 isoforms, including a novel isoform, named Oct 2.7. Compared with Oct-2 (isoform 2.1), the deduced Oct-2.7 sequence has an additional 22 amino acids close to the N-terminus and a novel 76-amino-acid C terminus resulting from alternative splicing, with retention of the last intron that is spliced out in all other isoforms. Although Oct-2.7 has intact POU specific and POU-homeo domains, it is unable to bind to the octamer motif, unlike all other known isoforms. Like Oct-1, both Oct-2.1 and Oct-2.7 can activate basal beta-casein gene promoter activity. However, activation by Oct-2.7, which is independent of DNA binding, is significantly lower than that by Oct-2.1. Moreover, deletion of the first 114 amino acids at the N-terminus of Oct-2.1 has no effect on activation; this does not support previous reports of the presence of an inhibitory domain in this region. PMID- 17285330 TI - Multi-detector computed tomography demonstrates smoke inhalation injury at early stage. AB - A multitrauma victim was transported to our trauma centre. Smoke inhalation injury was suspected based on trauma history and clinical examination. The first trauma computer tomography (CT) obtained 2.8 h after the injury revealed subtle ground-glass opacifications with mainly peribronchial distribution and patchy peribronchial consolidations centrally in the left lung. A repeated scan showed a more distinctive demarcation of the peribronchial opacities, further substantiating the clinically verified smoke inhalation injury. The golden standard for diagnosing smoke inhalation injury still is fibroptic bronchoscopy examination. This paper shows that lesions typical to smoke inhalation injury appear much earlier than previously reported. Whether assessment of smoke inhalation injury severity using CT could clinically benefit patients is controversial and still requires further research. Multi-detector computed tomography is readily available in trauma centres and to simply neglect its potential as a diagnostic tool in some inhalation injury would be unwise. PMID- 17285331 TI - Histopathological and radiological investigations of the influence of botulinum toxin on the submandibular gland of the rat. AB - The aim of the study was to correlate the sonographic features of Botox A injection in rat submandibular gland with the histopathological changes. Fifteen Wistar albino rats were randomly assigned to 2 groups. Group 1 (control group) consisted of 5 animals not given any substance. Group 2 was divided as "a" and "b" each consisting of 5 animals. A median cervical incision has been performed to the rats in group 2 and 2.5 U Botulinum toxin A reconstituted 0.1 ml physiologic saline was injected into the right gland. Sonograms were obtained before the application, at the first day of the Botox A application, in addition to group 2a on the 14th day, and on 28th day to group 2b. Gland size was lower in group 2a and 2b comparing to control group. The gland size of group 2b was lower than group 2a. There was no change in vascularization. There was no other histopathological change except lymphocytic infiltration in group 2. It was observed that Botox A injection does not have a direct effect on the cells in submandibular gland but it causes a homogenic shrinking in gland size without atrophy. PMID- 17285332 TI - Intraoral sebaceous carcinoma. AB - Intraoral sebaceous carcinoma (SC) is a rare tumour in the oral cavity thought to arise from malignant transformation of oral sebaceous glands. To our knowledge, only six cases of intraoral SC have been reported in the English language literature. The purpose of the present article is to report an additional case and review the literature. PMID- 17285333 TI - In vivo measurement of the shear modulus of the human vocal fold: interim results from eight patients. AB - The shear modulus of the vocal fold is an essential parameter required to enhance our understanding of how the vocal fold operates, to develop mathematical models of phonatation, and to provide benchmarks to quantify the effectiveness of surgical procedures. The authors announced the successful deployment of an instrument to measure vocal fold elasticity in vivo last year, and now present the data taken from eight patients in vivo. The shear modulus was measured at the mid-membranous point, in a transverse direction with respect to the axis drawn between the anterior commissure and vocal process. The range of mean shear modulus results is 701-2,225 Pa, with a mean value of 1,371 Pa. PMID- 17285334 TI - Stabilization and comparison of TOP and Bracketing perimetric strategies using a threshold spatial filter. AB - BACKGROUND: To evaluate a new perimetric spatial filter that takes into account relations of dependence between regions of the glaucomatous visual field. METHODS: 51 glaucoma patients and 30 controls were examined using the Octopus 1-2 3 on four occasions using program 32; two with TOP and two with Bracketing (BRA) strategy. Each threshold was replaced by a filtered threshold, calculated as the mean of its own value and the four points best correlated with it, weighted with the correlation coefficient (r) that relates them. RESULTS: Application of the filter had minimal effect on the absolute mean defect (MD) but reduced the square root of loss variance (sLV) by 17.6% in TOP and 28.8% in BRA, increasing the similarity between their results. Filtered TOP and BRA thresholds were more similar than those obtained in the two unfiltered BRA examinations. Filtering reduced the value of short fluctuation by 28.6% in TOP and 45.4% in BRA and reduced sLV fluctuation by 14.3% in TOP and 24.2% in BRA, thus harmonizing the two strategies for these two parameters (p > 0.05). The influence of filtering on MD fluctuation was minimal (p > 0.05). In normal subjects the number of points beyond 5 dB of normality (not reproducible false scotomas) reduced from 1.5% to 0.2% in TOP and from 4.9% to 1.6% in BRA, while in glaucoma patients changes were minimal. CONCLUSIONS: The proposed spatial filter stabilized perimetric results, acting with greater effect on BRA than on TOP, making their results more similar. PMID- 17285335 TI - Stiffness gradient in the crystalline lens. AB - BACKGROUND: While the overall stiffness of the lens has been measured in a number of studies, the knowledge about the stiffness distribution within the lens is still limited. The purpose of this study was to determine the stiffness gradient in the human crystalline lens. A secondary purpose was to determine whether the stiffness gradient depends on age. METHODS: The local dynamic stiffness was measured in 10 human crystalline lenses (age range: 19 to 78 years). The lenses were stored at -70 degrees C before being measured. The influence of freezing on the mechanical properties has been determined in a previous study. A small oscillating probe was used to measure the local dynamic shear modulus as a measure of lens stiffness. The measurements were taken in the cross-sectional plane through the lens equator. RESULTS: The local dynamic shear modulus varied with location for all tested lenses. The central stiffness of the oldest lens (78 years) was 10(4) times higher than the youngest (19 years) lens. The equatorial stiffness of the oldest lens was 10(2) times higher than the youngest lens. For the older lenses, the centre was 5.8-210 times stiffer than the periphery, as opposed to earlier results described by Fisher (1971), who found that the periphery was up to 3 times softer than the centre for lenses younger than 70 years-old. For the three youngest lenses (19 to 49 years), the periphery was 2.2 16.6 times stiffer than the centre. CONCLUSIONS: The dynamic stiffness of the crystalline lens varies with location within the lens. The stiffness gradient depends on the age of the lens. The results of the 10 lenses indicate that the stiffness of both centre and periphery increase with age, but at a different rate. PMID- 17285336 TI - Removal of residual subfoveal perfluoro-n-octane liquid. PMID- 17285337 TI - Vitreous findings in optic disc pit maculopathy based on optical coherence tomography. AB - BACKGROUND: To assess vitreous findings in optic disc pit maculopathy using Optical Coherence Tomography (OCT). METHODS: Thirty-eight eyes of 38 patients (14 51 years of age) with macular detachment associated with optic disc pit maculopathy were included in the study. The patients were divided into two groups. In group 1, 16 eyes were studied by OCT at presentation and after surgical treatment. In group 2, 22 eyes were examined by OCT only after treatment. In both groups thorough vitreous examination was performed over the macula and the optic disc. All patients were operated by the macular buckling procedure. RESULTS: Vitreous abnormalities were found in 28 out of 38 eyes (74%) of both groups. In group 1, 10 of the 16 eyes had vitreous traction on the macula at presentation. The traction started from the optic disc and terminated to the macula. The posterior hyaloid that exerted the traction between the points of adhesion at the optic disc and the macula had a course parallel to the retinal surface in 9 of the 10 cases. Postoperatively, vitreous traction on the macula was not found. Of the remaining 6 eyes 4 had complete or partial posterior vitreous detachment. In group 2, 8 eyes had vitreous strands over the optic disc and 5 eyes posterior vitreous detachment. In the remaining 9 cases no vitreous involvement was noticed. CONCLUSIONS: OCT was able to detect vitreous abnormalities such as vitreomacular traction, vitreous strands over the optic disc and complete or partial posterior vitreous detachment associated with optic disc pit maculopathy. Our observations support the view that the abnormal vitreous over the macula and optic disc is likely to play a role in the development of macular elevation in cases with optic disc pit. Prospective OCT studies could further assist to better understand the role of vitreous in this disease. PMID- 17285339 TI - Does water delivery affect pelvic floor? Ultrasound evaluation of perineal function. AB - OBJECTIVE: The aim of the study is to analyse urethral mobility and excursion of the pubo-rectal angle, using perineal ultrasound, after normal vaginal delivery and water delivery. MATERIALS AND METHODS: A total of 52 primiparous women were enrolled: 25 who had delivery in water (W Group), 27 who had delivery without using water (NW Group). Every woman underwent perineal ultrasound assessment at 6 months after having given birth. The following parameters were assessed: urethral mobility during Valsalva's manoeuvre, movement of the puborectal sling angle during contraction of the levator ani muscle. RESULTS: Data obtained show that the urethral mobility during Valsalva's manoeuvre is higher in the W Group (34.9 degrees) in comparison to the NW Group (29.5 degrees), without statistically significant differences. The excursion of the pubo-rectal sling angle resulted lower in the W Group (8.7 degrees) than in the NW Group (11.0 degrees), without statistically significant differences. CONCLUSION: The present study found no statistically differences in pelvic floor, using perineal ultrasound, between water and "non-water" delivery. PMID- 17285338 TI - Sinus pericranii: diagnostic and therapeutic considerations in 15 patients. AB - INTRODUCTION: Sinus pericranii (SP) is a rare, usually asymptomatic condition characterized by a large communication between the intra- and the extracranial venous drainage pathways in which blood may circulate bidirectionally through dilated veins of the skull. We describe our diagnostic and therapeutic experience with SP, with a special focus on the vascular analysis of digital subtraction angiography (DSA). METHODS: DSA images of 15 patients were evaluated with regard to the delay in opacification of the scalp vessels, the absence or distortion of the superficial cortical veins in the vicinity of the SP, the drainage patterns of the superior sagittal sinus, and the degree of maturation of the venous outlets of the brain. SP were classified either as "dominant", if the main stream of contrast flow used the SP to drain the brain bypassing usual venous outlets, or as "accessory", if only a small part of the venous outflow occurred through the extradiploic vessels. RESULTS: All patients presented with a nonpulsatile, soft-tissue mass. The lesion was on the midline in 14 of 15 patients, frontal in 12 patients, and parietal in 2 patients. In 13 patients, associated intracranial venous anomalies were present, eight of which were developmental venous anomalies. Seven patients had a dominant SP, and eight an accessory SP. CONCLUSION: SP can be considered the cutaneous sign of an underlying venous anomaly. If treatment is contemplated, analysis of the drainage pattern of the SP has to be performed. Treatment should be avoided in dominant SP or if its accessory role constitutes the only collateral pathway of an underlying venous anomaly. PMID- 17285340 TI - Amphetamine abuse in pregnancy: the impact on obstetric outcome. AB - OBJECTIVE: To determine whether pregnant women with amphetamine abuse developed more obstetric complications than non-drug abuser pregnant women. MATERIALS AND METHODS: A retrospective case control study was undertaken. Pregnant women with amphetamine abuse who delivered between January 2002 and December 2003 were compared to control pregnant women. RESULTS: Pregnant women who abused amphetamine were more likely to develop anemia, preterm delivery, thick meconium stained amniotic fluid, and delivered small for gestational age neonates. However, cephalopelvic disproportion was less frequently found in the amphetamine abuse group. CONCLUSION: Pregnant women who abuse amphetamine experience more obstetric complications than the non-drug abuser. This information may be useful to medical personnel who are caregivers of these pregnant women to provide adequate perinatal care. PMID- 17285341 TI - Many faces of drebrin: from building dendritic spines and stabilizing gap junctions to shaping neurite-like cell processes. AB - In this review we consider the multiple functions of developmentally regulated brain protein (drebrin), an actin-binding protein, in the formation of cellular polarity in different cell types. Drebrin has a well-established role in the morphogenesis, patterning and maintenance of dendritic spines in neurons. We have recently shown that drebrin also stabilizes Connexin-43 containing gap junctions at the plasma membrane. The latest literature and our own data suggest that drebrin may be broadly involved in shaping cell processes and in the formation of stabilized plasma membrane domains, an effect that is likely to be of crucial significance for formation of cell polarity in both neuronal and non-neuronal types. PMID- 17285343 TI - A comparison of Hox3 and Zen protein coding sequences in taxa that span the Hox3/zen divergence. AB - The class 3 Hox genes of insects have diverged--in expression domain and functional role during embryogenesis--compared to those of other bilaterians. Whereas the canonical ortholog (Hox3) is involved in axial patterning of the embryonic body, the insect ortholog (zen) is involved in extraembryonic development. In this paper, we present sequence data from the centipede Strigamia maritima, the collembolan Folsomia candida, and the insect Thermobia domestica. With these data, complete coding sequences are now known for orthologs in all four arthropod classes and all three great bilaterian clades. We make use of this large Hox3/Zen ortholog data set to define differences in the protein sequences encoded by insect zen genes compared to all other Hox3 orthologs. Folsomia and Thermobia are particularly relevant to determining when zen diverged from Hox3 over evolutionary time. Intriguingly, the orthologs of these two species have some protein sequence features typical of Hox3 and some typical of Zen, and they differ from one another for these features. PMID- 17285342 TI - Differential morphology and composition of inclusions in the R6/2 mouse and PC12 cell models of Huntington's disease. AB - The histological hallmark feature of Huntington's disease (HD) and other polyglutamine repeat diseases is the presence of intracellular inclusions. Much work has been devoted to trying to determine the relationship between inclusion formation and neuronal injury. However, little attention has been paid to the variability and characteristics of inclusions themselves. Here, we characterize the morphological and biochemical composition of inclusions in both a transgenic mouse model (R6/2 line) and an inducible cell culture model of HD (iPC12Q74). We identified several morphologically distinct kinds of inclusions in different locations (nuclei, cytoplasm and cellular processes). Ubiquitin colocalized completely with all of these inclusions in both the iPC12Q72 and R6/2 models. In the inclusions in iPC12Q74 cells, the 20S and 11S proteasome subunits colocalized variably, and the 19S subunit did not colocalize at all. In inclusions in R6/2 mouse neurons, the 20S subunit colocalized completely, but neither the 11S nor the 19S subunits colocalized at all. While the role of inclusions in the pathogenesis of HD continues to be debated, we suggest that the content and structure of inclusions vary considerably, not only from cell to cell but even within individual cells. Their role in the pathogenesis of HD is likely to depend on their location as well as their composition. PMID- 17285345 TI - N-terminal iron-mediated self-cleavage of human frataxin: regulation of iron binding and complex formation with target proteins. AB - Frataxin is an iron-binding mitochondrial matrix protein that has been shown to mediate iron delivery during iron-sulfur cluster and heme biosynthesis. Mitochondrial processing peptidase (MPP) yields a form of human frataxin corresponding to residues 56-210. However, structural and functional studies have focused on a core structure that results from an ill-defined cleavage event at the N-terminus. Herein we show that the N-terminus of MPP-processed frataxin shows a unique high-affinity iron site and that this iron center appears to mediate a self-cleavage reaction. Moreover, the N-terminus appears to block previously defined iron-binding sites located on the carboxylate-rich surface defined by the helix (alpha1) and the beta-sheet (beta1), most likely through electrostatic contact with the carboxylate-rich surface on the core protein, as well as inhibiting iron-promoted binding of the iron-sulfur cluster assembly scaffold partner protein, ISU. The physiological significance of iron-mediated release of the N-terminal residues from this anionic surface is discussed. PMID- 17285346 TI - Differences in the in vitro susceptibility of mono-eukaryotic cultures of Histomonas meleagridis, Tetratrichomonas gallinarum and Blastocystis sp. to natural organic compounds. AB - Currently, all pharmaceuticals for the treatment or prophylaxis of blackhead disease (histomonosis) caused by the flagellate Histomonas meleagridis are banned from the market. Consequently, great interest exists on the finding of alternative drugs for the abatement of histomonosis. In this study, carvacrol, Cassia oil, an essential oil (EO) mixture containing thyme and rosemary EO and a Quillaja saponaria saponin were examined using in vitro assays for antiprotozoal and antibacterial activity testing established against cloned xenic cultures of different isolates of Histomonas meleagridis, Tetratrichomonas gallinarum and Blastocystis sp. Whereas similar minimal lethal concentrations (MLCs) of five Histomonas isolates were obtained for both carvacrol and the EO mixture as well as for the saponin, significantly different MLCs were observed for them with Cassia oil, ranging from 0.25 up to 0.50 microl/ml. Testing the Blastocystis isolates, different MLCs were obtained for all substances, whereas the Tetratrichomonas gallinarum isolates showed identical susceptibilities. The effects are independent of the bacteria, underlining the need of well-defined protozoan cultures for these investigations. PMID- 17285344 TI - Ancient connection between NKL genes and the mesoderm? Insights from Tlx expression in a ctenophore. AB - In recent years, evo-devo studies on non-bilaterian metazoans have improved our understanding of the early evolution of animal body plans. In particular, works on cnidarians suggested that contrary to classical views, the mesoderm originated far before the emergence of the Bilateria. In this context, a synthesis of genomic and functional data concerning the Antennapedia (Antp) superclass of homeobox genes suggested that early in animal evolution, each of the three germ layers was under the control of one cluster of Antp genes. In particular, the patterning and differentiation of the mesoderm was under the control of the NKL cluster. The ctenophores stand as a key taxon with respect to such issues because unlike other non-bilaterian phyla, their intermediate germ layer satisfies the strict embryological definition of a mesoderm. For that reason, we investigated the only known member of the NKL group in Ctenophora, a gene previously isolated from Pleurobrachia and attributed to the Tlx family. In our analysis of the NKL group, this ctenophore gene branches as the sister-group of bilaterian Tlx genes, but without statistical support. The expression pattern of this gene was revealed by in situ hybridisation in the adult ctenophore. The expression territories of PpiTlx are predominantly ectodermal, in two distinct types of ciliated epidermal cells and in one category of gland cells. We also identified a probable endodermal site of expression. Because we failed to detect any mesodermal expression, the results do not provide support to the hypothesis of an ancient functional association between the NKL group and the mesoderm. PMID- 17285348 TI - Gargoyle-like features in lysosomal diseases involving glycosaminoglycans. PMID- 17285347 TI - Upper airway mechanics and post-hypoxic ventilatory decline during NREM sleep. AB - Termination of hypoxia results in a transient ventilatory decline referred to as post-hypoxic ventilatory decline (PHVD). We wished to determine whether PHVD is due to changes in ventilatory motor output or upper airway mechanics. We studied 19 healthy normal subjects (15 men, 4 women) during stable non-REM (NREM) sleep. Subjects were exposed to multiple episodes of brief (3 min) hypoxia that terminated with one breath of 100% FI(O2). Minute ventilation (V (I)), tidal volume (V (T)), timing, and upper airway resistance (R (ua)) were measured during the control, hypoxia, and for the first six breaths immediately after cessation of hypoxia. In addition, we measured diaphragmatic electromyograms (EMGdia) via surface electrodes in four subjects. V (I) and V (T) decreased during the recovery period to a nadir of 81 and 83% of room air control, respectively. However, there was no significant change in respiratory frequency or upper airway resistance during the post-hypoxic recovery period. Decreased V (I) was associated with a comparable decrease in EMGdia. We conclude that: (1) PHVD occurs in normal humans during NREM sleep, (2) there is no evidence of post hypoxic frequency decline in humans during NREM sleep, and (3) PHVD is centrally mediated and not driven by upper airway mechanics. PMID- 17285349 TI - Lack of efficacy of antibiotic-impregnated shunt systems in preventing shunt infections in children. AB - OBJECTIVE: Shunt infection is a common and serious complication of cerebrospinal fluid (CSF) shunting most commonly caused by skin flora contamination at surgery. Recent studies indicate that the use of antibiotic-impregnated (AI) shunt systems may reduce the risk of postoperative shunt infections. We evaluated the incidence of shunt infections associated with the use of AI shunt catheters and compared it with the incidence associated with standard non-AI catheters. MATERIALS AND METHODS: All shunt procedures performed by one surgeon using AI catheters were reviewed. An equal number of consecutive shunt procedures performed by the same surgeon using non-AI catheters were reviewed from the period immediately before the introduction of the AI system. Patients with <9 months of follow-up were excluded; all shunt infections and shunt-related complications were recorded. The proportions of infected shunts in the AI and control groups were compared using a chi (2) analysis. CONCLUSION: We reviewed 160 shunt procedures (80 per group). The infection rate was 5.0% among patients with AI catheters compared with 8.8% in the control group (P = 0.534, Fischer's exact). The average time to infection was similar between the two groups. Among the AI group, the shunt infection rate did not differ between ventricular catheter, distal catheter revisions, and revisions of ventricular and peritoneal tubing. In contrast with other reports, we found no significant reduction in the pediatric CSF shunt infection rate with the use of AI shunt systems. Any recommendation for or against the routine use of AI systems in children requires a prospective, blinded, randomized-controlled trial with adequate power. PMID- 17285352 TI - [Report on notifications with respect to section sign 21 German Transfusion Act for 2003 and 2004]. AB - Data with respect to the section sign 21 Transfusion Act concerning collection, manufacture, imports and exports show consolidation, but a non-plausible discrepancy due to the considerably lower figures of product consumption. Failure of numerous institutions to report their consumption precludes an interpretation as surplus supply. Homologous blood donations peaked in 2003 (6.8 million) with 2.4 million thereof being apheresis, which decreased to 1.6 million in 2004. Manufacture of red cells reached a peak of 4.52 million in 2004, with 74% attributable to the Red Cross. Reported consumption differs so significantly that the PEI considers utilising the legal possibility to compare the distribution lists of blood services with submitted user data. The 2.4 million litres plasma for fractionation in 2003 constitute the hitherto highest value, with a 62% share of apheresis; the latter decreased in 2004 to 50% of 1.9 million litres, paralleled by a decrease in commercial plasma centres. The new request (2004) for figures of fractionation in Germany revealed 734,224 litres, i.e. 45% of the calculated available amount on the German market. Isolated consideration of the German situation concerning plasma derivatives is impossible due to complex trade and manufacture in various federal states. Assessment of the supply situation is further impaired by missing data from users. Regarding haemophilia treatment, an improvement is intended by establishing a German Haemophilia Register. PMID- 17285350 TI - The association of bone mineral density measures with incident cardiovascular disease in older adults. AB - The associations of volumetric and areal bone mineral density (BMD) measures with incident cardiovascular disease (CVD) were studied in a biracial cohort of 2,310 older adults. BMD measures were inversely related to CVD in women and white men, independent of age and shared risk factors for osteoporosis and CVD. INTRODUCTION: We investigated the associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with incident cardiovascular disease (CVD) in older adults enrolled in the Health, Aging, and Body Composition study. METHODS: The incidence of CVD was ascertained in 2,310 well-functioning white and black participants (42% black; 55% women), aged 68-80 years. aBMD measures of the hip were assessed using DXA. Spine trabecular, integral, and cortical vBMD measures were obtained using QCT. RESULTS: During an average follow-up of 5.4 years, 23% of men and 14% of women had incident CVD. Spine vBMD measures were inversely associated with incident CVD in white men [HR(integral)=1.39, 95% CI 1.03-1.87; HR(cortical)=1.38, 95% CI 1.03-1.84], but not in black men. In women, aBMD measures of the total hip (HR = 1.36, 95% CI 1.03-1.78), femoral neck (HR = 1.44, 95% CI 1.10-1.90), and trochanter (HR = 1.34, 95% CI 1.04-1.72) exhibited significant associations with CVD in blacks, but not in whites. All associations were independent of age and shared risk factors between osteoporosis and CVD, and were not explained by inflammatory cytokines or oxidized LDL. CONCLUSION: Our results provide support for an inverse association between BMD and incident CVD. Further research should elucidate possible pathophysiological mechanisms linking osteoporosis and CVD. PMID- 17285351 TI - Enhanced tolerance of the rat myocardium to ischemia and reperfusion injury early after acute myocardial infarction. AB - It is now recognized that changes occurring during cardiac remodeling may influence the tolerance of the myocardium to ischemic stress. Therefore, the present study investigated the response of the post-infarcted heart to ischemia in an experimental model of ischemia and reperfusion injury and the possible underlying mechanisms. Acute myocardial infarction (AMI) was induced in Wistar male rats by ligating the left coronary artery (AMI, n = 13), while sham-operated rats were used as controls (SHAM, n = 11). At 2 weeks, cardiac dysfunction was observed in AMI, as indicated by the reduction of the left ventricular EF%. Isolated hearts were then subjected to 30 min of zero-flow global ischemia followed by 45 min of reperfusion. Ischemic contracture was significantly depressed in AMI hearts. Postischemic left ventricular end diastolic pressure (LVEDP45) in mmHg and LDH release in IU/g were markedly decreased; LVEDP45 was 52.1 (7.5) for AMI vs 96.6 (7.5),P < 0.05 and LDH release was 7.5 (1.0) in AMI vs 11.4 (0.56) in SHAM, P < 0.05. This response was associated with 2-fold increase in HSP70 expression in AMI hearts (noninfarcted segment), P < 0.05 vs SHAM and 1.7 fold increase in the expression of the phospho-HSP27, P < 0.05, while the expression of PKCepsilon was shown to be 1.4-fold less in AMI, P < 0.05. In conclusion, the post-infarcted heart seems to be resistant to ischemiareperfusion injury and heat shock protein 70 and 27 may be involved in this response. PMID- 17285353 TI - [Biobanks]. AB - Biobanks are an important tool of genetic epidemiology, which investigates the role of genetic factors and their interaction with environmental factors (in a broad meaning) for the occurrence of diseases in human populations. Its aim is to understand the influence of genetics on the development of diseases, their course and the clinical implications, with the final goal to improve prevention, diagnostics and therapy. The extraordinary development of genetics in the last decades - with respect to the understanding of the meaning of genes for human health, as well as the availability of cost-effective high throughput methods in the lab, has opened enormous opportunities to study genetic factors. In addition, access to large samples of patients or from the population is needed. This can be realized via biobanks. Large biobanks with 500,000 or more participants are being established or planned in the UK, Japan, Australia, Sweden and the US. However, in Germany only two smaller activities are ongoing, KORA-gen in the south and POPGEN in the north. Possibilities to reach larger numbers for Germany, based on existing cohorts or disease networks, are discussed. For the implementation and use of biobanks, stringent ethical boundary conditions have to be taken into account. The opinion of the German National Ethics Council on Biobanks for Research as well as the new recommendations of the Telematic Platform (TMF), which has been developed in close collaboration with the Data Protection Officers, improve transparency and legal security. PMID- 17285357 TI - Metabolic modulation in heart failure: the coming of age. PMID- 17285358 TI - Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: comparative studies against doxorubicin and mitoxantrone. AB - Anthracyclines and anthracenediones are important oncotherapeutics; however, their use is associated with irreversible and cumulative cardiotoxicity. A novel aza-anthracenedione, pixantrone (BBR 2778), was developed to reduce treatment related cardiotoxicity while retaining efficacy. This study evaluates the cumulative cardiotoxic potential of pixantrone compared with equiactive doses of doxorubicin and mitoxantrone in both doxorubicin-pretreated and doxorubicin-naive mice. CD1 female mice were given doxorubicin 7.5 mg/kg (once weekly for 3 weeks) followed 6 weeks later by either sterile 0.9% saline, doxorubicin 7.5 mg/kg, pixantrone 27 mg/kg, or mitoxantrone 3 mg/kg (once weekly for 3 weeks). A second group of CD1 female mice were given 2 cycles of either sterile 0.9% saline, pixantrone 27 mg/kg, doxorubicin 7.5 mg/kg, or mitoxantrone 3 mg/kg (once weekly for 3 weeks). Animals were sacrificed at different time points for histopathologic examination of the heart. In the doxorubicin-pretreated mice, further exposure to doxorubicin or mitoxantrone resulted in a significant worsening of pre-existing degenerative cardiomyopathy. In contrast, pixantrone did not worsen pre-existing cardiomyopathy in these animals. Only minimal cardiac changes were observed in mice given repeated cycles of pixantrone, while 2 cycles of doxorubicin or mitoxantrone resulted in marked or severe degenerative cardiomyopathy. These animal studies demonstrate the reduced cardiotoxic potential of pixantrone compared with doxorubicin and mitoxantrone. Exposure to pixantrone did not worsen pre-existing cardiomyopathy in doxorubicin-pretreated mice, suggesting that pixantrone may be useful in patients pretreated with anthracyclines. PMID- 17285359 TI - Antioxidant protection of edible oils. AB - The ability of different cooking oils to withstand oxidation was investigated in relation to their native antioxidant capacity [measured as the Ferric Reducing/Antioxidant Power (FRAP) value]. The antiperoxidation effect of the presence of the Chinese herbs, du-zhong (Cortex Eucommia ulmoides) and ginseng (Panax ginseng C.A. Mayer) in corn oil was also investigated over 26 days' storage at 55 degrees C. Results showed that sesame oil had the highest FRAP value (803 microM), followed by canola oil (400 microM), and sunflower, peanut, corn and olive oils (100-153 microM). Oils with higher intrinsic antioxidant content showed higher resistance to oxidation, although this was not statistically significant. Corn oil to which was added the herbs du-zhong, ginseng or both had increased resistance to oxidation (conjugated diene level and lipid peroxide formation) over 26 days. FRAP values of the oil/herb mixtures decreased during this time, implying utilisation of herbal antioxidants. Results have implications for increasing the shelf-life and usage time of cooking oils by addition of herbs which can increase resistance of the oil to oxidation. Results have implications also for health, as it is possible that ingestion of these herbs could increase resistance of polyunsaturated fatty acids of cell membranes and lipoproteins to oxidation within the body. PMID- 17285360 TI - Assessing the dynamics of nuclear glucocorticoid-receptor complex: adding flexibility to gene expression modeling. AB - A retrospective analysis was performed to modify our fourth-generation pharmacodynamic model for glucocorticoid receptor (GR) dynamics with incorporation of more physiological features. This modified model was developed by integrating previously reported free cytosolic GR and GR mRNA data following single (10, 50 mg/kg) and dual (50 mg/kg at 0 and 24 hr) intravenous doses of methylprednisolone (MPL) in adrenalectomized (ADX) male Wistar rats with several in vitro studies describing real-time kinetics of the transfer of rat steroid receptor complex from the cell cytosol to the nucleus. Additionally, free hepatic cytosolic GR and its mRNA data from a chronic infusion dosing study of MPL (0.1 and 0.3 mg/kg/hr) in male ADX Wistar rats were used to verify the predictability of the model. Incorporation of information regarding in vitro receptor kinetics allowed us to describe the receptor-mediated pharmacogenomic effects of MPL for a larger variety of genes in rat liver from microarray studies. These included early responsive gene like CCAAT/enhancer binding protein-beta (CEBP-beta), a transcription factor, as well as the later responsive gene for tyrosine aminotransferase (TAT), a classical biomarker of glucocorticoid (GC) genomic effects. This more mechanistic model of GR dynamics can be applied to characterize profiles for a greater number of genes in liver. PMID- 17285361 TI - Optimal design for multiresponse pharmacokinetic-pharmacodynamic models - dealing with unbalanced designs. AB - This paper addresses the problem of determining D-optimal designs for multiresponse pharmacokinetic-pharmacodynamic (PKPD) experiments where data on each response variable can be collected at different times. Most previous multiresponse model optimal design applications have considered the case where all response variables are measured at the same time points. However in practice it may not be possible to have all responses measured at the same sampling times. We propose an optimal design method to take into account the unbalanced nature of the problem. The method developed was applied to a PKPD problem that involved describing the time course of drug plasma concentrations, heart rate and mean arterial blood pressure for both a fixed effects and mixed effects regression model. Additionally a simulation study was carried out in NONMEM for one such population optimal design problem. PMID- 17285362 TI - A simple absorption model for dose-escalating studies. AB - A simple model for absorption that generalizes zero and first order absorption processes is discussed. We show how traditional methods can be used to investigate how reasonable this model is, and discuss the effects of the absorption model on classical PK parameters. The methods are illustrated with two real-life data sets from dose-escalating studies. PMID- 17285363 TI - Large-scale automated analysis of location patterns in randomly tagged 3T3 cells. AB - Location proteomics is concerned with the systematic analysis of the subcellular location of proteins. In order to perform high-resolution, high-throughput analysis of all protein location patterns, automated methods are needed. Here we describe the use of such methods on a large collection of images obtained by automated microscopy to perform high-throughput analysis of endogenous proteins randomly-tagged with a fluorescent protein in NIH 3T3 cells. Cluster analysis was performed to identify the statistically significant location patterns in these images. This allowed us to assign a location pattern to each tagged protein without specifying what patterns are possible. To choose the best feature set for this clustering, we have used a novel method that determines which features do not artificially discriminate between control wells on different plates and uses Stepwise Discriminant Analysis (SDA) to determine which features do discriminate as much as possible among the randomly-tagged wells. Combining this feature set with consensus clustering methods resulted in 35 clusters among the first 188 clones we obtained. This approach represents a powerful automated solution to the problem of identifying subcellular locations on a proteome-wide basis for many different cell types. PMID- 17285364 TI - Layer-specific 3D residual deformations of human aortas with non-atherosclerotic intimal thickening. AB - Data relating to residual deformations in human arteries are scarce. In this paper we investigate three-dimensional residual deformations for intact strips and for their separate layers from human aortas in their passive state. From 11 abdominal aortas with identified anamnesis, 16 pairs of rings and axial strips were harvested, and the rings cut open. After 16 h images of the resulting geometries were recorded, and the strips were separated into their three layers; after another 6 h images were again recorded. Image processing and analysis was then used to quantify residual stretches and curvatures. For each specimen histological analysis established that the intima, media and adventitia were clearly separated, and the separation was atraumatic. Axial in situ stretches were determined to be 1.196+/-0.084. On separation, the strips from the adventitia and media shortened (between 4.03 and 8.76% on average), while the intimal strips elongated on average by 3.84% (circumferential) and 4.28% (axial) relative to the associated intact strips. After separation, the adventitia from the ring sprang open by about 180 degrees on average, becoming flat, the intima opened only slightly, but the media sprang open by more than 180 degrees (as did the intact strip). The adventitia and intima from the axial strips remained flat, while the media (and the intact strip) bent away from the vessel axis. This study has shown that residual deformations are three dimensional and cannot be described by a single parameter such as 'the' opening angle. Their quantification and modeling therefore require consideration of both stretching and bending, which are highly layer-specific and axially dependent. PMID- 17285365 TI - A new approach to the non-unique probe selection problem. AB - Identification of biological agents in a sample is a relevant problem in medicine. A model to this problem consists of selecting optimal oligonucleotide probe sets for use in hybridization experiments in which target viruses or bacteria are to be identified in biological samples. In such an experiment the presence or absence of these targets is determined by observing whether selected probes bind to their corresponding sequences. The problem is to select a probe set that is able to uniquely identify targets while containing a minimal number of probes. In this paper we describe a heuristic algorithm that produced feasible solution sets that for large, real data sets contain significantly fewer probes than those obtained using other methods. A description of the problem, our approach, and the results are presented. We developed a C++ program and a GUI (Graphical User Interface) to run real and simulated instances of the problem. PMID- 17285367 TI - Analysis of verbal communication during teaching in the operating room and the potentials for surgical training. AB - BACKGROUND: Verbal communication in the operating room during surgical procedures affects team performance, reflects individual skills, and is related to the complexity of the operation process. During the procedural training of surgeons (residents), feedback and guidance is given through verbal communication. A classification method based on structural analysis of the contents was developed to analyze verbal communication. This study aimed to evaluate whether a classification method for the contents of verbal communication in the operating room could provide insight into the teaching processes. METHODS: Eight laparoscopic cholecystectomies were videotaped. Two entire cholecystectomies and the dissection phase of six additional procedures were analyzed by categorization of the communication in terms of type (4 categories: commanding, explaining, questioning, and miscellaneous) and content (9 categories: operation method, location, direction, instrument handling, visualization, anatomy and pathology, general, private, undefinable). The operation was divided into six phases: start, dissection, clipping, separating, control, closing. RESULTS: Classification of the communication during two entire procedures showed that each phase of the operation was dominated by different kinds of communication. A high percentage of explaining anatomy and pathology was found throughout the whole procedure except for the control and closing phases. In the dissection phases, 60% of verbal communication concerned explaining. These explaining communication events were divided as follows: 27% operation method, 19% anatomy and pathology, 25% location (positioning of the instrument-tissue interaction), 15% direction (direction of tissue manipulation), 11% instrument handling, and 3% other nonclassified instructions. CONCLUSION: The proposed classification method is feasible for analyzing verbal communication during surgical procedures. Communication content objectively reflects the interaction between surgeon and resident. This information can potentially be used to specify training needs, and may contribute to the evaluation of different training methods. PMID- 17285368 TI - Routine intraoperative aspiration of gallbladder during laparoscopic cholecystectomy. AB - BACKGROUND: Technical modifications and methods for gallbladder dissection to minimize the risk of gallbladder perforation during laparoscopic cholecystectomy (LC) are described. The authors aimed to investigate the effects of gallbladder aspiration during LC on the operative and postoperative course of patients. METHODS: For this study, 200 patients undergoing LC for symptomatic cholelithiasis were randomly divided into two groups. Gallbladders were aspirated before dissection in group A (n = 100), and they were not aspirated in group B (n = 100). Operative and postoperative data on the patients were collected. RESULTS: The rate of gallbladder perforation was significantly lower in group A than in group B (p = 0.0003). The operative time was significantly shorter in group A (46.70 +/- 15.93 min) than in group B (60.75 +/- 22.09 min) (p = 0.047). Postoperative complications were more numerous in group B. The hospital stay was significantly longer in group B (1.55 +/- 0.81 days) than in group A (1.3 +/- 0.5 days; p = 0.004). CONCLUSION: The findings demonstrate the advantages of gallbladder aspiration in elective cases. PMID- 17285366 TI - Temozolomide in the treatment of an invasive prolactinoma resistant to dopamine agonists. AB - Prolactinomas are common tumors of the anterior pituitary gland. While conventional therapies, including dopamine agonists, transsphenoidal surgery and radiotherapy, are usually effective in controlling tumor growth, some patients develop treatment-resistant tumors. In this report, we describe a patient with an invasive prolactinoma resistant to conventional therapy that responded to the administration of the alkylating agent, temozolomide. PMID- 17285369 TI - Tissue ingrowth and bowel adhesion formation in an animal comparative study: polypropylene versus Proceed versus Parietex Composite. AB - BACKGROUND: The optimal prosthesis for laparoscopic ventral hernia repair would combine excellent parietal surface tissue ingrowth with minimal visceral surface adhesiveness. Currently, few data are available from randomized trials comparing the commercially available prostheses. METHODS: In a pig model designed to incite adhesions, three 10 x 15-cm pieces of mesh (Proceed, Parietex Composite [PCO], and polypropylene [PPM]) were randomly positioned intraperitoneally in each of 10 animals using sutures and tack fixation. After a 28-day survival, the amount of shrinkage, the area and peel strength of visceral adhesions, the peak peel strength, the work required to separate mesh from the abdominal wall, and a coefficient representing the adhesiveness of tissue ingrowth were averaged for each type of mesh and then compared with the averages for the other prostheses. The histologic appearance of each prosthesis was documented. RESULTS: Proceed had more shrinkage (99.6 cm2) than PCO (105.8 cm2) or PPM (112 cm2), although the difference was not statistically significant. The mean area of adhesions to PCO (11%) was significantly less than for Proceed (48%; p < 0.008) or PPM (46%; p < 0.008). Adhesion peel strength was significantly less for PCO (5.9 N) than for Proceed (12.1 N; p < 0.02) or PPM (12.9 N; p < 0.02). According to a filmy-to dense scale of 1 to 5, adhesions were more filmy with PCO (1.7) than with PPM (2.9) or Proceed (3.7) (p < 0.007). Peak peel strength from the abdominal wall was significantly higher for PCO (17.2 N) than for Proceed (10.7 N) or PPM (10 N; p < 0.002). The histology of each prosthesis showed a neoperitoneum only with PCO. CONCLUSIONS: With less shrinkage, fewer and less dense adhesions to the viscera, and significantly stronger abdominal wall adherence and tissue ingrowth at 28 days in this animal study, PCO was superior to both Proceed and PPM in all categories. Furthermore, PCO demonstrated all the favorable qualities needed in an optimal prosthesis for laparoscopic ventral hernia repair, including the rapid development of a neoperitoneum. PMID- 17285370 TI - Surgeons' experience with laparoscopic fundoplication after the early personal experience: does it have an impact on the outcome? AB - BACKGROUND: The adverse outcomes of laparoscopic fundoplication are more likely during the initial 20 cases performed by each individual surgeon. This study aimed to evaluate the impact of substantial surgical experience versus experience beyond the learning curve on the early and late objective and subjective results. METHODS: The patients were divided into two groups according to the surgeon. In group 1 (n = 230), all the patients underwent surgery by a surgeon with substantial experience in laparoscopic fundoplication. In group 2 (n = 118), the patients were treated by a total of seven surgeons whose personal experience exceeded the individual learning curve, but was distinctively less than that of the group 1 surgeon. RESULTS: The conversion rate was 2.2% in group 1 and 4.4% in group 2. The median operating time was 65 min in group 1 and 70 min in group 2 (p = 0.0020). The occurrence of immediate complications was 3.5% in group 1 and 7.6% in group 2 (p = 0.0892). At 6 months after surgery, 7.4% of the patients in group 1 and 16.1% of the patients in group 2 reported that dysphagia disturbed their daily lives (p = 0.0115). The late subjective results, including postoperative symptoms and evaluation of the surgical result, were similar in the two groups. CONCLUSIONS: Substantial experience with the procedure is associated with a shorter operating time and somewhat fewer complications, conversions, and early dysphagia episodes. This supports the provision of expert supervision even after the initial learning phase of 20 individual procedures. The patients' long-term subjective symptomatic outcome was similar in the two groups. Substantial experience does not provide better late results than surgical experience beyond the learning curve. PMID- 17285371 TI - Transanal endoscopic microsurgery in the treatment of rectal carcinoid tumor. AB - BACKGROUND: This study aimed to assess the efficacy of transanal endoscopic microsurgery (TEM) in the treatment of rectal carcinoid tumor. METHODS: Between May 1994 and April 2006, 27 patients with rectal carcinoid tumor underwent TEM, and their clinical data were reviewed retrospectively. RESULTS: The TEM procedure was performed as a primary excision (n = 14) or as completion surgery after incomplete resection by endoscopic polypectomy (n = 13). The average size of a primary tumor was 9.1 mm (range, 5-13 mm), and the average distance of the tumor from the anal verge was 8.5 cm. The mean duration of the operation was 51.6 min. Minor morbidities, transient soilage, and mild dehiscence occurred in two cases (7.4%). Histopathologically, all tumors were localized within the submucosal layer showing typical histology without lymphatic or vessel infiltration, and both deep and lateral surgical margins were completely free of tumors. Among 13 cases of completion surgery after endoscopic polypectomy, 4 (30.8%) were histologically shown to have a residual tumor in the specimens obtained by TEM. No additional radical surgery was performed. The mean follow-up period was 70.6 months, and no recurrence was noted. CONCLUSION: The results indicate that TEM is a safe, minimally invasive procedure for the local excision of rectal carcinoid tumors, particularly those in the proximal rectum. Furthermore, for patients with microscopic positive margins after endoscopic polypectomy, TEM can be an effective surgical option for complete removal of residual tumors. PMID- 17285372 TI - Role of intraoperative enteroscopy for surgical decision making with Crohn's disease. AB - BACKGROUND: This study aimed to assess the role of intraoperative enteroscopy (IOE) in determining surgical treatment. METHODS: The IOE procedure was performed for 30 patients with Crohn's disease. The degree of stricture and the presence of active ulcer were examined. Preoperative diagnoses and intraoperative findings obtained by inspection and palpation were noted and compared with the IOE findings. RESULTS: Of the 78 intestinal strictures observed by IOE (42%), 33 were not found by preoperative examination. Of the 45 strictures confirmed by IOE to be severe (<15 mm in diameter), 8 were judged to be mild (15-25 mm in diameter) or were not even identified by intraoperative inspection and palpation. Active ulcer was found at 12 of 33 mild strictures, and all 12 strictures were surgically corrected. Of 11 severe strictures detected by IOE at previous surgical sites, 9 were found preoperatively, and 4 were judged to be mild on the basis of inspection and palpation. Stricture was found at the ileocecal valve by IOE in seven patients, but was not diagnosed preoperatively in two of these patients. CONCLUSION: Intraoperative enteroscopy provides useful information regarding the status of the lumen in patients with Crohn's disease. PMID- 17285373 TI - Laparoscopic lymphatic mapping and sentinel lymph node detection in colon cancer: technical aspects and preliminary results. AB - BACKGROUND: The utility of lymph node mapping to improve staging in colon cancer is under evaluation. Laparoscopic colectomy for colon cancer has been validated in multicentric trials. This study assessed the feasibility of lymph node mapping in laparoscopic colectomy for colon cancer. METHODS: From March 2004 to December 2005, 22 patients were studied. Before resection, 2 to 3 ml of Patent Blue V dye was injected subserosally around the tumor. Colored lymph nodes were marked as sentinel nodes (SNs) with metal clips, and laparoscopic colectomy with lymphadenectomy was completed as normal. In SNs, multiple 4-microm slices at 50 microm intervals were stained with hematoxylin and eosin and examined. Anticytokeratin antibody immunostaining was applied in doubtful cases. Other lymph nodes were examined with multiple slices at 100- to 500-microm intervals by standard methods. RESULTS: The SN detection rate was 100%, although ex vivo lymph node mapping was necessary for an obese patient. Five patients (22.7%) were SN positive. There was one false-negative SN (16.7%). In two cases (9.1%) with aberrant lymphatic drainage, lymphadenectomy was extended. The SN reflected the status of the regional lymph nodes in 21 patients (95.4%). Accuracy was 95.4%, and negative predictive value was 94.1%. CONCLUSIONS: Laparoscopic lymphatic mapping and SN removal is feasible in laparoscopic colectomy for colon cancer. Although the false-negative rate was high (16.7%), the overall results are promising and justify prospective studies to determine the real accuracy and false-negative rate for the technique. PMID- 17285374 TI - A comparison of 399 open and 568 laparoscopic gastric bypasses performed during a 4-year period. AB - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass surgery (RYGB) was introduced at the authors' institution 5 years ago. The authors analyzed the short- and long term results of this procedure compared with those for the same procedure using the laparotomy approach over the same period. METHODS: Retrospective analysis of a prospectively collected bariatric database used the outcome end points used by the American Society of Bariatric Surgery (ASBS) and the American College of Surgeons (ACS) in their center of excellence programs. RESULTS: From January 2001 to July 2005, 568 laparoscopic and 399 open gastric bypasses were performed at Vanderbilt University. The patients were from the same bariatric surgery program and therefore received the same pre- and postoperative care. The hospital length of stay in the laparoscopic group was significantly shorter (2.5 +/- 2.4 days) than in the open group (3.7 +/- 3.7 days; p = 0.001). The procedure time was significantly shorter in the laparoscopic group (164 +/- 50 min) than in the open group (195 +/- 50 min; p = 0.0001). The follow-up assessment response at 2 years was 76.6%. At 2 years, the excess weight loss (EWL) was significantly greater in the laparoscopic group (71.3% +/- 18.4%) than in the open group (67.3% +/- 15.3%; p = 0.03). The wound infection rate was significantly higher in open group (9.2%) than in the laparoscopic group (1.7%; p = 0.001). There was no significant difference in 30-day mortality: open (0.50%) versus laparoscopic (0.17%; p = 0.371). There was no significant difference in the 30-day reoperation rate between the open (2.4%) and laparoscopic (2.6%; p = 0.705) groups. The 30-day readmission rate was similar in the open (5.0%) and laparoscopic (5.2%; p = 0.852) groups, as was the rate of leakage from the gastrojejunostomy in the open (0.50%) and laparoscopic (0.35%; p = 0.127) groups. The conversion rate from laparoscopic procedure to laparotomy was 1.7%. CONCLUSION: In the authors' institution, a laparoscopic bariatric surgery program with a very low rate of morbidity and mortality has been introduced. Operative time, hospital stay, and wound complications are reduced with the laparoscopic approach. The laparoscopic and open procedures are equally safe, with equivalent 30-day mortality, readmission, reoperation, and gastrojejunostomy leakage rates. PMID- 17285375 TI - Prospective histologic evaluation of intra-abdominal prosthetics four months after implantation in a rabbit model. AB - BACKGROUND: Placement of an intraperitoneal prosthetic is required for laparoscopic ventral hernia repair. The biocompatibility of these prosthetics determines the host's inflammatory response, scar plate formation, tissue ingrowth, and subsequent mesh performance, including prosthetic compliance and prevention of hernia recurrence. We evaluated the host response to intraperitoneal placement of several prosthetics currently used in clinical practice. METHODS: A 4-cm x 4-cm piece of mesh was implanted on intact peritoneum in New Zealand white rabbits. The mesh types included expanded polytetrafluoroethylene (ePTFE) (DualMesh), ePTFE and polypropylene (Composix, heavyweight polypropylene), polypropylene and oxidized regenerated cellulose (Proceed, midweight polypropylene), and polypropylene (Marlex, heavyweight polypropylene). At four months, standard hematoxylin and eosin and Milligan's trichrome stains of the mesh-tissue interaction were analyzed by three observers blinded to the mesh types. Each specimen was evaluated for scar plate formation, inflammatory response, and tissue ingrowth. Each of these three categories was graded on a standard scale of 1-4 (1 = normal tissue and 4 = severe inflammatory response). The scores were analyzed using Wilcoxon rank sum test with p < 0.05 as significant. RESULTS: Ten samples of each mesh type were evaluated. There was no difference in tissue incorporation between the groups. The mean scar plate formation was greater in the heavyweight polypropylene meshes than for DualMesh (p = 0.04). With Proceed, the reduction in scar plate formation compared with that for Composix and Marlex approached statistical significance (p = 0.07). The mean number of inflammatory cells was greater around the ePTFE when compared with the midweight polypropylene (p = 0.02) but equal to the other meshes. CONCLUSIONS: The four prosthetic materials evaluated in this study demonstrate comparable host biocompatibility as evidenced by the tissue ingrowth. Scar plate formation around DualMesh was significantly less than that around Composix and Marlex. Interestingly, more inflammatory cells were noted surrounding the DualMesh which was equal to that of the heavyweight meshes. Proceed, a midweight polypropylene mesh, has the potential for improved patient tolerance compared to heavyweight polypropylene meshes based on its favorable histologic findings. PMID- 17285376 TI - Percutaneous treatment of giant abdominal hydatid cysts. PMID- 17285377 TI - What is a meant when a laparoscopic surgical procedure is described as "safe"? AB - BACKGROUND: The literature on laparoscopic surgery contains many studies concluding that a procedure is "safe." This study aimed to review systematically articles from the past 10 years that judged a laparoscopic technique for colon resection and anastomosis to be "safe." METHODS: The authors searched the Medline database from January 1995 to August 2005 using the search terms "laparoscopic," "colon," and "safe," selecting studies of laparoscopic colon resection or laparoscopic techniques of colonic anastomosis. They calculated exact 95% confidence intervals around estimates of the risk for death reported in the studies to determine the upper limit of the possible risk for death in a study reporting no deaths. RESULTS: Of 135 studies matching the search criteria, 41 (30%) described operations involving laparoscopic colonic resection or anastomosis. These studies enrolled a mean number of 233 subjects. There were 26 retrospective studies, 12 prospective studies, 2 randomized control trials, and 1 case report. The estimated upper 95% confidence limits for studies reporting mortality ranged from 1.66% to 97.5%. Of the studies that reported mortality and concluded that laparoscopic colon surgery is "safe," 77.8% could not exclude a mortality rate higher than 5%. CONCLUSION: Many studies concluding that laparoscopic colon surgery is "safe" could not exclude a high risk of operative mortality. The term "safe" is not a useful descriptor of the relative safety of laparoscopic surgical procedures, and statements about the safety of a surgical procedure should be justified with precise estimates and confidence intervals of the risk for adverse events. PMID- 17285379 TI - Accuracy of administrative health data for the diagnosis of upper gastrointestinal diseases. AB - BACKGROUND: The use of administrative health data is increasingly common for the study of various medical and surgical diseases. The validity of diagnosis codes for the study of benign upper gastrointestinal disorders has not been well studied. METHODS: The authors abstracted the charts for 590 adult patients who underwent upper gastrointestinal endoscopy between January 1, 2000 and June 30, 2001 in Toronto, Ontario, Canada. Clinical diagnoses from medical records were compared with International Classification of Diseases Version 9 (ICD-9) codes in electronic hospital discharge abstracts. The primary analysis aimed to determine the sensitivity, specificity, and positive predictive value (PPV) of a most responsible "esophagitis" diagnosis code for the prediction of esophagitis. Secondary analyses determined the performance characteristics of the diagnostic codes for esophageal ulcer, esophageal stricture, gastroesophageal reflux disease (GERD), gastritis, gastric ulcer, and duodenal ulcer. RESULTS: The authors linked 500 patient records to electronic discharge abstracts. When listed as the most responsible diagnosis for admission, the ICD-9 codes for esophagitis showed a sensitivity of 46.79%, a specificity of 98.83%, and a PPV of 94.81%. When listed as a secondary diagnosis, the ICD-9 codes showed a sensitivity of 70.51%, a specificity of 97.67%, and a PPV of 93.22%. The diagnostic properties of ICD-9 codes for GERD (most responsible, secondary) were as follows: sensitivity (56.10%, 78.66%), specificity (98.51%, 96.73%), and PPV (94.84%, 92.14%). CONCLUSIONS: The ICD-9 diagnosis codes for benign upper gastrointestinal diseases are highly specific and associated with strong PPVs, but have poor sensitivity. PMID- 17285378 TI - Laparoscopic liver resection: results for 70 patients. AB - BACKGROUND: Laparoscopy is slowly becoming an established technique for liver resection. This procedure still is limited to centers with experience in both hepatic and laparoscopic surgery. Preliminary reports include mainly minor resections for benign liver conditions and show some advantage in terms of postoperative recovery. The authors report their experience with laparoscopic liver resection, the evolution of the technique, and the results. METHODS: From 1999 to 2006, 70 laparoscopic liver resections were performed using a procedure similar to resection by laparotomy. RESULTS: There were 38 malignant tumors (54%) and 32 benign lesions (46%). The malignant tumors were mainly hepatocellular carcinomas (19 of 24 patients had cirrhosis). The tumor mean size was 3.8 +/- 1.9 cm (range, 2.2-8 cm). There were 19 major hepatectomies, 34 uni- or bisegmentomies, and 17 atypical resections. The operative time was 227 +/- 109 min. Conversion to laparotomy was required for seven patients (10%), mainly for continuous bleeding during transection. Nine patients (13%) required blood transfusion. One patient had both brisk bleeding and gas embolism from a tear in the section line of the right hepatic vein requiring laparoscopic suture. Blood loss and transfusion requirements were significantly lower in recent than in early cases and in resections with prior vascular control than in those without such control. Postoperative complications were experienced by 11 patients (16%), including one bleed from the hepatic stump requiring hemostasis and two subphrenic collections requiring percutaneous drainage. One cirrhotic patient died of liver failure after resection of a partially ruptured tumor. No ascites was observed in other cirrhotic patients. The mean hospital stay was 5.9 days. CONCLUSION: The study results confirm that laparoscopic liver resection, including major hepatectomies, can be safely performed by laparoscopy. PMID- 17285380 TI - Reverse-alignment surgical skills assessment. AB - BACKGROUND: During the course of certain laparoscopic procedures, a surgeon may encounter circumstances where the camera and working instruments are not aligned along the same axis. When the alignment is off by 180 degrees, the laparoscope is pointed directly at the surgeon and a mirror image of the operative field is created. Under reverse alignment conditions, surgeons often become disoriented and task performance may be degraded. The aim of this study is to measure the degree to which reverse alignment conditions impair the performance of operators of varying laparoscopic surgical skill and experience. METHODS: Nineteen general surgery residents and 3 attending surgeons were tested in a video trainer. A task designed to simulate tack placement during laparoscopic ventral hernia repair was created. Time required to successfully complete this task in both forward and reverse alignment conditions was measured for all participants. For this study, the impact of visual-spatial discordances of angles other than 180 degrees on task performance was not assessed. Data regarding prior laparoscopic case volume and MISTELS scores were collected for each resident. RESULTS: Significant and strong correlations were observed between resident experience and individual MISTELS scores. No significant correlation was found between reverse image times and any other surrogate measure of experience or skill for the residents. All study participants required a significantly longer period of time to complete the simulated tack task in reverse alignment compared to forward alignment conditions. Attendings required 65% more time and resident times increased by 470%. Attendings completed the task significantly faster than residents in reverse alignment conditions. CONCLUSIONS: Reverse-alignment surgical skills can be improved with experience, but may require a volume of cases exceeding that encountered in residency training. Reverse image skills are not derivative from surgical skills developed in a video trainer with forward orientation. PMID- 17285381 TI - Gastrojejunal anastomotic stricture after Roux-en-Y gastric bypass: ambulatory management with the Savary-Gilliard dilator. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is currently one of the most frequently performed procedures for the surgical treatment of morbid obesity. The success of this procedure's restrictive component requires a small gastrojejunostomy (GJ), which occasionally results in stenosis. The treatment of choice for this complication is balloon dilation. This study aimed to evaluate the feasibility and safety of ambulatory management for stenosis of the GJ using endoscopically guided Savary-Gilliard dilators. METHODS: Between January 1998 and October 2003, 769 patients underwent RYGBP. The mean age of these patients was 38 +/- 12 years, and their mean body mass index (BMI) was 43 +/- 6 kg/m2. Of these 769 patients, 520 (68%) underwent open surgery and 249 (32%) underwent laparoscopic RYGBP. Patients suspected of GJ stenosis were referred for upper gastrointestinal endoscopy. Those who presented with stenosis were managed endoscopically with Savary-Gilliard dilators. RESULTS: Stenosis at the GJ was confirmed in 53 patients (6.9%). A total of 71 dilations were performed for these patients, resulting in a mean of 1.3 dilations per patient. One dilation was needed for 41 patients (75.5%), two dilations for 9 patients (16.9%), three dilations for 3 patients (5.7%), and four dilations 1 patient (1.9%). The patients subjected to open RYGBP required a mean of 1.57 dilations, and those who had laparoscopic RYGBP required mean of 1.08 dilations. The mean time for the first dilation was 51 +/- 28 days after surgery (range, 20-178 days). All the dilations were performed in ambulatory settings. One patient (1.9%) was admitted after GJ dilation for pain. He was discharged without symptoms after 2 days with no need for invasive procedures. CONCLUSIONS: The management and treatment of GJ stenosis after RYGBP can be effectively accomplished in ambulatory settings using endoscopically guided Savary-Gilliard dilators, with good and safe results. PMID- 17285382 TI - Short- and midterm outcomes of laparoscopic surgery compared for 131 patients with rectal and rectosigmoid cancer. AB - BACKGROUND: This study aimed to clarify and compare the short- and midterm surgical outcomes of laparoscopic surgery for rectal and rectosigmoid cancer. METHODS: Between June 1992 and December 2004, 131 selected patients with cancer of the rectum (n = 60) and rectosigmoid (n = 71) underwent laparoscopic surgery. The indications for laparoscopy included a preoperative diagnosis of T1/T2 tumor in the rectum and T1-T3 tumors in the rectosigmoid. RESULTS: The mean follow-up period was 42 months. The procedures included anterior resection for 117 patients, abdominoperineal resection for 11 patients, Hartmann's procedure for 1 patient, and restorative proctocolectomy for 1 patient. Conversion to an open procedure occurred for four patients (3.1%). Postoperative complications developed in 29 patients (22.1%), including anastomotic leakage in 14 patients (11.8%). The length of hospital stay for the rectal cases was significantly longer than for the rectosigmoid cases (10 vs 7 days; p = 0.0049). The tumor node metastasis (TNM) stages included 0 (n = 14), I (n = 72), II (n = 15), III (n = 29), and IV (n = 1). Recurrences were experienced by 13 patients, including local recurrence (n = 7) and recurrences involving the liver ((n = 2), lung (n = 3), and distant lymph nodes (n = 1). The 5-year disease-free and overall survival rates were, respectively 91.7% and 97.9% for stage I, 86.7% and 90.9% for stage II, and 77.1% and 90.0% for stage III. CONCLUSIONS: Laparoscopic surgery is feasible and safe for selected patients with rectal or rectosigmoid cancer. The selected patients in this study experienced favorable short- and midterm outcomes. PMID- 17285383 TI - Evaluation of the mechanical strength and patency of functional end-to-end anastomoses. AB - BACKGROUND: Although many mechanical devices are being developed for functional end-to-end anastomosis (FETEA), the best choice remains to be determined. The mechanical strength of each device is an important factor associated with anastomotic leakage. In turn, anastomotic patency is related to postoperative stenosis. This study examined the bursting pressure and circumference of several FETEAs. METHODS: Young domestic pigs were used in this study. In experiment 1, a 10-cm segment of intestine was transected using an EndoGIA 60 blue, EndoGIA 60 green, or GIA 60 blue stapler, and the bursting pressure of each instrument's mechanical staple line was examined. In experiment 2, after FETEA had been created with EndoGIA 60 blue, the bursting sites were examined, and the bursting pressures of buttressed and nonbuttressed FETEA were measured and compared. In experiment 3, the circumference of FETEA was compared between the closed technique and reinforcement. RESULTS: The bursting pressure of EndoGIA 60 blue was significantly higher than that of the other devices. When an anastomotic crotch was buttressed, the bursting pressure (44 +/- 13 mmHg) was significantly increased over that of the nonbuttressed FETEA (27.5 +/- 5.8 mmHg; p < 0.05). The circumference of FETEA using the wide technique (92.7 +/- 2.3 mm) was larger than that using the offset technique (55.7 +/- 5.8 mm). CONCLUSIONS: The bursting pressure of the mechanical staple line using the EndoGIA 60 stapler was the strongest. Functional end-to-end anastomosis was stronger when created with buttress of an anastomotic crotch, and larger circumferences were created with the wide technique. PMID- 17285384 TI - Intraoperative cholangiography facilitates simple transcystic clearance of ductal stones in units without expertise for laparoscopic bile duct surgery. AB - BACKGROUND: In the absence of facilities and expertise for laparoscopic bile duct exploration (LBDE), most patients with suspected ductal calculi undergo preoperative endoscopic duct clearance. Intraoperative cholangiography (IOC) is not performed at the subsequent laparoscopic cholecystectomy. This study aimed to investigate the rate of successful duct clearance after simple transcystic manipulations. METHODS: This prospective study investigated 1,408 patients over 13 years in a unit practicing single-session management of biliary calculi. For the great majority, IOC was attempted. Abnormalities were dealt with by flushing of the duct, glucagon injection, Dormia basket trawling, choledochoscopic transcystic exploration, or choledochotomy. RESULTS: Of 1,056 cholangiograms performed (75%), 287 were abnormal (27.2%). Surgical trainees, operating under supervision, successfully performed 24% of all cholangiograms. Of 396 patients admitted with biliary emergencies, 94.1% had abnormal cholangiograms. Of the 287 patients with abnormal IOCs, 9.4% required no intervention, 18% were clear after glucagon and flushing, and 13% were cleared using Dormia basket trawling under fluoroscopy. A total of 95 patients required formal LBDE, and 2 required postoperative endoscopic retrograde cholangiopancreatography (ERCP). No postoperative ERCP for retained stones was required after simple transcystic manipulation. Eight conversions occurred, one during a transcystic exploration. Follow-up evaluation continued for as long as 6 years in some cases. Two patients had recurrent stones after LBDE and a clear postoperative tube cholangiogram. CONCLUSION: In this series, 10% of the abnormal cholangiograms occurred in patients without preoperative risk factors for bile duct stones. Altogether, 88 IOCs (31%) were cleared after either simple flushing or trawling with a Dormia basket. Formal LBDE was not required for 40% of abnormal cholangiograms. Simple transcystic manipulations to clear the bile ducts justify the use of routine IOC in units without laparoscopic biliary expertise. PMID- 17285385 TI - A reliable method for monitoring intraabdominal pressure during natural orifice translumenal endoscopic surgery. AB - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) provides surgical access to the peritoneal cavity without skin incisions. The NOTES procedure requires pneumoperitoneum for visualization and manipulation of abdominal organs, similar to laparoscopy. Accurate measurement of the pneumoperitoneum pressure is essential to avoid potentially deleterious effects of intraabdominal compartment syndrome. A reliable method for monitoring pneumoperitoneum pressures during NOTES has not been identified. This study evaluated several methods of monitoring intraabdominal pressures with a standard gastroscope during NOTES. METHODS: Four female pigs (25 kg) were sedated, and a single-channel gastroscope was passed transgastrically into the peritoneal cavity. Pneumoperitoneum was achieved via a pressure insufflator through a percutaneous, intraperitoneal 14-gauge catheter. Three other pressures were recorded via separate catheters. First, a 14-gauge percutaneous catheter passed intraperitoneally measured true intraabdominal pressure. Second, a 14-gauge tube attached to the endoscope was used to measure endoscope tip pressure. The third pressure transducer was connected directly to the accessory channel of the endoscope. The abdomen was insufflated to a range of pressures (10-30 mmHg), and simultaneous pressures were recorded from all three pressure sensors. RESULTS: Pressure correlation curves were developed for all animals across all intraperitoneal pressures (mean error, -4.25 to -1 mmHg). Endoscope tip pressures correlated with biopsy channel pressures (R2 = 0.99). Biopsy channel and endoscope tip pressures fit a least-squares linear model to predict actual intraabdominal pressure (R = 0.99 for both). Both scope tip and biopsy channel port pressures were strongly correlative with true intraabdominal pressures (R2 = 0.98 and R2 = 0.99, respectively). CONCLUSION: This study demonstrates that monitoring pressure through an endoscope is reliable and predictive of true intraabdominal pressure. Gastroscope pressure monitoring is a useful adjunct to NOTES. Future NOTES procedures should incorporate continuous intraabdominal pressure monitoring to avoid the potentially deleterious effects of pneumoperitoneum during NOTES. This can be achieved by the integration of pressure-monitoring capabilities into gastroscopes. PMID- 17285386 TI - Comparison of dexamethasone, metoclopramide, and their combination in the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. AB - BACKGROUND: Postoperative nausea and vomiting (PONV) are one of the most common complaints following anesthesia and surgery. This study was designed to evaluate the efficacy of dexamethasone, metoclopramide, and their combination to prevent PONV in patients undergoing laparoscopic cholecystectomy. METHODS: A total of 160 ASA physical status I and II patients were included in this randomized, double blind, placebo-controlled study. Patients were randomly assigned to 4 groups (n = 40 each): group 1 consisting of control patients administered 0.9% NaCl; group 2 patients received metoclopramide 10 mg just before the end of anesthesia; group 3 patients received dexamethasone 8 mg after the induction of anesthesia; and group 4 patients received dexamethasone 8 mg after the induction of anesthesia and metoclopramide 10 mg before the end of anesthesia. The incidence of PONV, mean visual analog pain scores at rest and on movement, time to the first request for analgesia, side effects, and well-being score were recorded during the first 24 h postoperatively. RESULTS: Data were analyzed using one-way analysis of variance (ANOVA) and the chi2 test, with p < 0.05 considered statistically significant. The total incidence of PONV was 60% with placebo, 45% with metoclopramide, 23% with dexamethasone, and 13% with the combination of dexamethasone plus metoclopramide. None of the dexamethasone plus metoclopramide group patients (p < 0.05 versus groups 1 and 2) and one dexamethasone group patient (p < 0.05 versus group 1) required antiemetic rescue, as compared with four patients in the metoclopramide group and six patients in the placebo group. Pain scores, the time to the first request for analgesia, and side effects were similar across the study groups. CONCLUSIONS: Dexamethasone and the combination of dexamethasone plus metoclopramide were more effective in preventing PONV than metoclopramide and placebo. PMID- 17285387 TI - Laparoscopic management of a nonobstetric emergency in the third trimester of pregnancy. AB - BACKGROUND: Laparoscopic management of nonobstetric acute abdominal pain during pregnancy remains controversial. A gestational age of 26 to 28 weeks has been considered the upper limit for laparoscopy by some authors. A case series of nonobstetric surgery in advanced pregnancy is reported. METHODS: Third-trimester patients who underwent surgery between 1997 and 2006 were reviewed. RESULTS: Laparoscopic surgery was performed for nonobstetric emergencies during the third trimester for 11 patients. Four patients underwent open surgery. The laparoscopic surgery group included five cholecystectomies, four appendectomies, and two adenexal surgeries. The laparoscopic surgery procedure was successfully completed for 10 patients. Of these 10 patients, 9 had no complications and went on to deliver a healthy term infant. One patient went into preterm labor after a laparoscopic appendectomy for perforated acute appendicitis with purulent peritonitis and delivered a viable infant at 34 weeks. Another patient at 29 weeks of gestation underwent a diagnostic laparoscopy for abdominal pain. Adenexal torsion of a large multicystic ovarian mass led to a laparotomy (obstetrician preference) and right salpingo-oophrectomy. Her postoperative course was complicated by an episode of sudden syncope, hypotension, and fetal distress on postoperative day 3. An emergent laparotomy showed hemoperitoneum attributable to bleeding from the ovarian pedicle. A cesarean section delivery of a preterm infant requiring neonatal resuscitation was performed. The open surgery group included four patients. Two of the patients underwent appendectomies at 35 and 33 weeks, respectively, followed by a term delivery. The remaining two patients underwent emergent colectomies with a cesarean section delivery at 31 and 38 weeks, respectively. CONCLUSIONS: This study demonstrated that laparoscopic surgery in the third trimester of pregnancy is feasible and can be performed safely with an acceptable risk to the fetus and the mother. Access to the pregnant abdomen is easily obtained. Space generally is not a problem, and there is minimal uterine manipulation. PMID- 17285388 TI - Esophageal motility disorders in the morbidly obese population. AB - BACKGROUND: Most studies investigating esophageal motility among the morbidly obese have focused on the relationship between lower esophageal sphincter (LES) pressure and gastroesophageal reflux disease (GERD). Very few studies in the literature have examined motility disorders among the morbidly obese population in general outside the context of GERD. This study aimed to determine the prevalence of esophageal motility disorders in obese patients selected for bariatric surgery. METHODS: A total of 116 obese patients (81 women and 35 men) selected for laparoscopic gastric banding underwent manometric evaluation of their esophagus from January to March 2003. Tracings were retrospectively reviewed for the end points of LES resting pressure, LES relaxation, and esophageal peristalsis. RESULTS: The study patients had a body mass index (BMI) of 42.9 kg/m2, and a mean age of 48.6 years. The following abnormal manometric findings were demonstrated in 41% of the patients: nonspecific esophageal motility disorders (23%), nutcracker esophagus (peristaltic amplitude >180 mmHg) (11%), isolated hypertensive LES pressure (>35 mmHg) (3%), isolated hypotensive LES pressure (<12 mmHg) (3%), diffuse esophageal spasm (1%), and achalasia (1%). Only one patient with abnormal esophageal motility reported noncardiac chest pain. CONCLUSIONS: Despite a high prevalence of esophageal dysmotility in our morbidly obese study population, there was a conspicuous absence of symptoms. Although the patients in this study were not directly questioned with regard to esophageal symptoms, several studies in the literature support our conclusion. PMID- 17285389 TI - Continuous perioperative insulin infusion therapy for patients with type 2 diabetes undergoing bariatric surgery. AB - BACKGROUND: Continuous insulin infusion (CII) is proven to decrease morbidity and mortality in surgical critical care patients. This study compared standard insulin therapy with CII in type 2 diabetes patients undergoing elective bariatric surgical procedures in a community hospital. METHODS: A retrospective review investigated 350 bariatric surgical patients with type 2 diabetes who underwent perioperative treatment of hyperglycemia using either standard insulin therapy or CII. The 182 patients in group 1 underwent glucose monitoring and subcutaneous insulin treatment every 6 h, whereas the 168 patients in group 2 had CII treatment beginning in the preoperative holding area and monitored hourly for the next 24 h. The two groups were similar in demographic characteristics. RESULTS: There were no significant hypoglycemic episodes with perioperative CII. The mean perioperative insulin required was 5.8 U/h. The patients receiving CII had fewer postprocedure cholecystectomies, but a higher number of port-site infections. CONCLUSIONS: Perioperative CII can be administered safely to diabetic patients undergoing bariatric surgery. The insulin requirements in this population are higher than expected. Our study showed a decrease in the number of postoperative cholecystectomies in the CII group, but no effect on the stricture rate and an increase in the number of patients with postoperative port-site infections. PMID- 17285390 TI - Appendicitis in the elderly: a change in the laparoscopic era. AB - BACKGROUND: Appendicitis in elderly patients is associated with significant morbidity and mortality. Early and correct diagnosis together with minimally invasive surgery can lead to more favorable outcomes than occurred in the prelaparoscopic era. METHODS: A retrospective review of 116 elderly patients (age > 60) from 1999 to 2004 is compared with the authors' previously published studies from 1978 to 1988 (n = 96) and from 1988 to 1998 (n = 113), respectively. RESULTS: In our current series (1999-2004), more cases were managed laparoscopically (n = 68) than with open surgery (n = 48). Perforated appendicitis cases resulted in significantly longer hospital stays, more complications, and longer operating time than nonperforated cases. The laparoscopic cases had significantly shorter lengths of hospital stay and fewer complications than open cases, and comparable operating times. As compared with our previous studies from 1978 to 1988) and from 1988 to 1998, the current series (1999-2004) consists of patients presenting with fewer classical symptoms. Computed tomography (CT) scanning was more accurate in the current study and more routinely used. The patients in the current series had more correct preoperative diagnoses. Perforated appendicitis was encountered less frequently and associated with fewer complications. The 4% mortality rate in the previous two series decreased to less than 1% in this series. CONCLUSION: Minimally invasive surgery combined with increased use and accuracy of preoperative CT scans has changed the clinical management of acute appendicitis in elderly patients, leading to decreased lengths of stay, decreased mortality, and more favorable outcomes. PMID- 17285391 TI - Port closure techniques. AB - BACKGROUND: Laparoscopic trocars do create wounds. This article aims to review and list different techniques used for closure of the fascia incision at trocar sites. METHODS: A literature search was performed for articles dealing with closure techniques. The author searched this subject in English on Medline by combining the words "trocar" and "hernia," as well as "Deschamps" and "Reverdin." All articles reporting techniques with their references were reviewed. RESULTS: The articles described many techniques in addition to classical closure using curved needles, including Grice needle, Maciol needles, Endoclose device, Carter Thomason device, Tahoe ligature device, Endo-Judge device, eXit puncture closure device, Lowsley retractor, spinal cord needles, dual hemostat, suture carrier, Riverdin and Deschamps needles, and Gore-Tex closure device. CONCLUSION: Three main groups of techniques were found with favor of extracorporeal manipulations under direct visualization. Old methods are sufficient and cost-effective. PMID- 17285392 TI - Laparoscopic radical cystectomy: an Italian survey. AB - BACKGROUND: Radical cystectomy with urinary diversion is the current gold standard procedure for muscle-invasive bladder cancer. However, laparoscopic radical cystectomy (LRC) has evolved rapidly worldwide during the past decade, despite its complexity due to both the demolitive step with management of a highly aggressive cancer and the reconstructive step. The authors performed a survey to assess the Italian experience with LRC and urinary diversion in an effort to point out the volume of the procedure in their country, providing some surgical details. METHODS: A total of 10 Italian urologic departments with experts in laparoscopic urologic surgery were contacted and asked to participate in a two-page survey concerning indications for cystectomy, laparoscopic technique, intra- and postoperative complications, and follow-up evaluation of the procedure when available. RESULTS: Five sites elected to participate, and a total of 83 LRCs were collected. All centers used five trocar ports. The mean operative time was 8 h and 40 min, and the estimated blood loss was 376 ml. In two cases, the procedure was converted to open surgery. Postoperative complications consisted of one urinary leakage, one fistula, and one atrium rupture. A retrieval sac was used in all cases. Urinary diversions consisted of 43 ileal conduits, 26 orthotopic diversions, and 14 other techniques. The mean follow-up period was 9 months (range, 1-36 months). No tumor seeding was recorded. CONCLUSIONS: The LRC procedure is feasible although technically demanding. The morbidity of this procedure is evident, but may be reduced with further experience. Bowel management and reconstruction remain the most challenging part of the procedure. PMID- 17285393 TI - Evaluation of the technical difficulty performing laparoscopic resection of a rectosigmoid carcinoma: visceral fat reflects technical difficulty more accurately than body mass index. AB - BACKGROUND: In general, visceral fat and adhesion greatly influence the technical difficulty in performing abdominal surgery. Body mass index (BMI) has been widely used to express the degree of obesity, but it does not always properly reflect the degree of visceral fat. This retrospective study investigated the impact of visceral fat on the operation time to examine whether a quantified visceral fat area (VFA) could be used as a sensitive predictor of technical difficulty in performing a laparoscopic resection of rectosigmoid carcinoma. METHODS: Between February 1999 and April 2004, 58 consecutive patients underwent a laparoscopically assisted sigmoidectomy or anterior resection. After a review of the medical charts, the relationship between the operation time and the following variables was analyzed: sex, depth of invasion, approach (medial-to-lateral, lateral-to-medial), subjectively graded degree of visceral fat and adhesion, history of previous abdominal surgery, and BMI. The correlations between VFA, VFA/body surface area (BSA) measured by the "FatScan," software package for quantifying the VFA from the preoperative CT images, and operation time were investigated. Next, the impact of the VFA amount on the early surgical outcome was examined. RESULTS: According to the intraoperative findings, two patients with a severe adhesion required a significantly longer operation time. A history of previous abdominal surgery was not a significant factor in the operation time. Instead, the VFA/BSA had a stronger correlation with the operation time than the BMI. A significantly longer operation time (209 +/- 42 vs 179 +/- 37 min; p = 0.031) was observed for the patients in the high VFA/BSA group (> or =85 cm(2)/m(2)) group than in the normal VFA/BSA group (<85 cm(2)/m(2)). CONCLUSION: For predicting the technical difficulty of performing a laparoscopic resection of rectosigmoid carcinoma, VFA/BSA may be a more useful index than BMI. PMID- 17285395 TI - Diffusion of surgical techniques in early stage breast cancer: variables related to adoption and implementation of sentinel lymph node biopsy. AB - BACKGROUND: Understanding how physicians acquire and adopt new technologies for cancer diagnosis and treatment is poorly understood, yet is critical to the dissemination of evidence-based practices. Sentinel lymph node biopsy (SLNB) has recently become a standard technique for axillary staging in early breast cancer and is an ideal platform for studying medical technology diffusion. We sought to describe the timing of SLNB adoption and patterns of surgeon interactions with the following educational sources: local university training program, surgical literature, national meetings/courses, national specialty centers, and other local surgeons. METHODS: A cross-sectional survey that used semistructured interviews was used to assess timing of adoption, practice patterns, and learning sources for SLNB among surgical oncologists and general surgeons in a single metropolitan area. RESULTS: A total of 44 eligible surgeons were identified; 38 (86%) participated. All surgical oncologists (11 of 11) and most general surgeons (26 of 27) had implemented SLNB. Surgical oncologists were older (mean 51 vs. 48 years, P = .02) and had used SLNB longer (6.1 vs. 3.3 years, P = .01) than general surgeons. By use of social network diagrams, surgical oncologists and the university training program were shown to be key intermediaries between general surgeons and national specialty centers. Surgeons in group practice tended to use more learning sources than solo practitioners. CONCLUSIONS: Surgical oncologists and university-based surgeons play key educational roles in disseminating new cancer treatments and therefore have a professional responsibility to educate other community physicians to increase the use of the most current, evidence based practices. PMID- 17285394 TI - The effect of laparoscopic Nissen fundoplication on laryngeal findings and voice quality. AB - BACKGROUND: This study aimed to report the need for an ear, nose, and throat (ENT) specialist to evaluate the laryngeal findings and the voice quality of patients with gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) symptoms before and after surgery. METHODS: For this study, 38 GERD patients who had a Reflux Symptom Index (RSI) score higher than 14 underwent complete assessment in the ENT department. Standard 24-h pH monitoring, esophageal motility assessment, a detailed ENT examination including the RSI, the Reflux Finding Score (RFS), and objective voice analysis were performed for all the patients before reflux surgery, then 6 to 8 months afterward. RESULTS: The subject's mean RSI scores were 25.45 +/- 7.5 before and 16.52 +/- 5.06 after surgery (p < 0.05), and the mean RFS scores were, respectively, 10.37 +/- 2.7 and 5.5 +/- 1.45 (p < 0.05). The pre- and postoperative differences in the RSI and RFS scores and the voice parameters were statistically significant. CONCLUSIONS: Objective voice analysis, RSI, and RFS can be used to evaluate the postoperative results for GERD patients with LPR symptoms. Examination of these patients by an ENT specialist is necessary before and after the operation. PMID- 17285396 TI - Regional nodal metastatic disease is the strongest predictor of survival in patients with thin vertical growth phase melanomas: a case for SLN Staging biopsy in these patients. AB - BACKGROUND: The benefit of sentinel lymph node (SLN) biopsy for patients with thin (< or =1.0 mm) melanomas, even for prognostic value, is controversial. This may partly result from the relatively small number and short follow-up of SLN positive patients in this group. Previously, we have shown that clinical regional nodal metastatic disease (RNMD) serves as a good surrogate for SLN positivity. Here, we use RNMD as a validated surrogate for SLN positivity and examine its prognostic value in a large pre-SLN group of patients with thin vertical growth phase (VGP) lesions who would today commonly be offered SLN biopsy in our practice. METHODS: Between 1972 and 1991, 472 patients with thin VGP melanomas with at least 10 years' follow-up were eligible for the study. Kaplan-Meier survival curves were computed for patients with and without RNMD. A multivariate Cox model and classification tree analysis were used to evaluate clinical and histopathologic predictors of survival. RESULTS: Sixty-seven patients (14.2%) developed recurrence, 53.7% of whom developed RNMD. Forty-five patients (9.5%) experienced melanoma-related deaths (MRD). The most statistically significant predictor of MRD was RNMD (hazard ratio [HR] 13.5, P < .0001). Thickness (HR 10.5, P = .004), axial location (HR 4.6, P = .001), and age >60 years (HR 2.7, P = .005) additionally were independently associated with an increased risk of MRD. RNMD patients demonstrated a 44.4% 10-year disease-specific mortality. CONCLUSIONS: RNMD was the most statistically significant factor associated with MRD in patients with thin VGP lesions. This supports the prognostic use of SLN biopsy in this group, recognizing that additional factors, including thickness, axial location, and older age were independently associated with a worse survival outcome. PMID- 17285397 TI - Surgical management of familial hyperparathyroidism. PMID- 17285398 TI - Treatment failure after percutaneous radiofrequency ablation for nonsurgical candidates with pulmonary metastases from colorectal carcinoma. AB - BACKGROUND: This study critically evaluated the local and overall treatment failure rates after percutaneous radiofrequency ablation (RFA) of pulmonary metastases from colorectal carcinoma. METHODS: Fifty-five nonsurgical candidates underwent RFA of colorectal pulmonary metastases. The primary end points of this study were local progression-free survival (PFS) and overall PFS. Univariate and multivariate analyses were performed to identify significant prognostic parameters for local and overall PFS. RESULTS: The local recurrence rate was 38%. For local PFS, univariate analysis demonstrated that the largest size of lung metastasis, the location of lung metastases, the post-RFA carcinoembryonic antigen level at 1 month, and the post-RFA carcinoembryonic antigen level at 3 months were significant prognostic indicators. In multivariate analysis, a largest size of lung metastasis of >3 cm and a post-RFA carcinoembryonic antigen level of >5 ng/mL at 1 month were independently associated with a reduced local PFS. The overall recurrence rate was 66%. For overall PFS, univariate analysis demonstrated that sex and the largest size of lung metastasis were significant prognostic indicators. In multivariate analysis, a largest size of lung metastasis of >3 cm was independently associated with a reduced overall PFS. CONCLUSIONS: RFA of colorectal pulmonary metastases may have a useful role in local disease control for nonsurgical candidates, but its efficacy in patients with a lung metastasis of >3 cm is limited. PMID- 17285399 TI - Update on uterine artery embolization for symptomatic fibroid disease (uterine artery embolization). AB - Transcatheter embolization of the uterine arteries for symptomatic fibroid disease has become an increasingly important alternative treatment. It is highly effective and well tolerated by most patients. Most notably, uterine artery embolization is associated with a short recovery period and is uterine sparing. To ensure the best chance for a safe and successful procedure, Interventional Radiologists should have familiarity with uterine artery anatomy, state of the art embolization techniques, and optimal patient selection and post procedure management. PMID- 17285400 TI - Paroxysmal nocturnal hemoglobinuria: complete resolution of an occluding inferior vena caval thrombus. AB - Paroxysmal nocturnal hemoglobinuria is a rare acquired autoimmune disease, and is frequently associated with venous thrombosis. A patient who developed thrombotic occlusion of the inferior vena cava is described. Treatment with heparin and urokinase, followed by oral anticoagulant, was effective in resolving abdominal symptoms. The venous thrombosis resolved completely, but the patient died during treatment of aplastic anemia. PMID- 17285401 TI - CT angiography in renal angiomyolipomas. AB - Renal angiomyolipomas are fat containing tumours, which are associated with a strong risk of hemorrhage due to the presence of abnormal vessels and pseudoaneurysms. We present three cases of ruptured renal angiomyolipomas with multiple or large pseudoaneurysms diagnosed by CT angiography which enabled emergent endovascular intervention; and propose CT angiography as the diagnostic modality of choice, particularly in emergency situations. PMID- 17285402 TI - Gastroduodenal intussusception. AB - Intussusception is a well-known condition that a portion of gut invaginates into the lumen of the immediate adjacent intestine. Intussusception in adult is rare, about 5% of all intussusceptions (Stubenbord and Thorbjarnarson in Ann Surg 172(2):306-310, 1970). We present a rare case of gastric gastrointestinal stromal tumors complicated with gastroduodenal intussusception. The preoperative diagnosis was made on multidetector CT and confirmed at operation. PMID- 17285403 TI - Assessment of disease activity in alveolar echinococcosis: a comparison of contrast enhanced ultrasound, three-phase helical CT and [(18)F] fluorodeoxyglucose positron emission tomography. AB - BACKGROUND: Objective of the present study was to assess activity or vascularization of focal liver lesions in alveolar echinococcosis (AE) using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) in comparison with contrast enhanced ultrasound (CEUS) and three-phase helical computed tomography (CT). METHODS: In this prospective study, 17 patients with confirmed AE of the liver were included (6 males, 11 females; average age: 59 +/- 16 years; average duration of disease: 10.5 years) and were then examined using FDG-PET, precontrast ultrasound (US), CEUS, and three-phase helical CT. We assessed metabolic activity (FDG-PET) and vascularization (CEUS and CT) of Echinococcus multilocularis specific hepatic lesions. RESULTS: FDG-PET identified increased metabolic activity in the corresponding lesions in seven patients (41.2%). A vascularization pattern of echinococcal lesions was visualized in 9 patients (52.9%) by CEUS and in 4 patients (23.5%) by CT. All positive FDG-PET findings were also positive at CEUS. CONCLUSIONS: There was association between findings of metabolic activity in AE at FDG-PET and vascularized lesions of the liver returned by CEUS. This suggests that CEUS may represent a cost-effective tool in the decision making to perform FDG-PET examination. PMID- 17285405 TI - A comparison of intravenous-based and epidural-based techniques for anesthesia and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy. AB - PURPOSE: We wished to compare the effectiveness of intravenous-based (IV) and epidural-based (EPI) techniques for anesthesia and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy. Effectiveness was compared in terms of reduction of postoperative pain and adverse events, and achieving a high level of patient satisfaction. METHODS: Thirty American Society of Anesthesiologists (ASA) physical status I-II patients aged more than 65 years, scheduled for laparoscopic cholecystectomy, were enrolled in this study. The patients in the IV group (n = 15) received modified neurolept anesthesia with droperidol 0.2 mgxkg(-1) and pentazocine 0.15-0.3 mgxkg(-1) (maximum dose of 1.0 mgxkg(-1)) and 60% nitrous oxide in oxygen, followed by postoperative intravenous infusion of 20 microgxml(-1) buprenorphine, provided with a patient-controlled analgesia pump programmed to deliver a bolus of 0.5 ml with a lockout interval of 15 min and a background infusion of 0.5 mlxh(-1). The patients in the EPI group (n = 15) had combined epidural analgesia and general anesthesia with sevoflurane and 60% nitrous oxide in oxygen, followed by the epidural infusion of a 0.125% bupivacaine and 5 microg x ml(-1) buprenorphine mixture by means of an on-demand analgesic system (bolus of 2 ml, lockout interval of 60 min, and background infusion of 2 mlxh(-1)). RESULTS: The quality of postoperative analgesia was similar in the two groups. The incidences of intraoperative hypotension and bradycardia and postoperative hypotension were significantly lower in the IV group than in the EPI group (P < 0.05). A significantly higher level of patient satisfaction was found in the IV group compared with that in the EPI group (P < 0.05). The major contributor to dissatisfaction in the EPI group was anxiety or discomfort associated with the epidural procedures. CONCLUSION: Modified neurolept anesthesia with pentazocine and postoperative i.v. analgesia with buprenorphine were superior to epidural-based techniques, in terms of hemodynamic stability and patient satisfaction, in elderly patients undergoing laparoscopic cholecystectomy. PMID- 17285406 TI - Effects of quazepam as a preoperative night hypnotic: comparison with brotizolam. AB - PURPOSE: The purpose of this study was to evaluate the effects of quazepam, a long-acting hypnotic, as a preoperative night medication in comparison with brotizolam, a shortacting hypnotic. METHODS: Two hundred patients (aged 30 to 70 years) admitted for elective general anesthesia at various hospitals were enrolled. Quazepam 15 mg, 30 mg, or 45 mg, or brotizolam 0.25 mg (40 patients each), was administered orally at 9 p.m. in the evening of the day before surgery. The control group (40 patients) did not receive any drugs. The quality of night sleep between the night during hospitalization and the night before surgery was compared by using a questionnaire. In the first 8 patients who received quazepam 15 mg, 30 mg, and 45 mg, the plasma concentrations of quazepam and its metabolites were measured 12 h after the drug administration, when the patients were brought into the operating room. RESULTS: In all the drug administered groups, the speed of falling asleep, sleeping state, and feeling of freshness in the morning improved compared to the previous night and compared to the control group; the frequency of nocturnal awakening and dreaming decreased, and the total duration of sleep the night before surgery increased. Total duration of sleep was significantly longer in the groups with quazepam 30 mg and 45 mg than in the control and brotizolam 0.25 mg groups. No patients were drowsy with plasma concentrations of quazepam of 30 to 65 ngxml(-1). CONCLUSION: The preoperative night hypnotics, quazepam and brotizolam improved sleep before surgery. As a preoperative night hypnotic, quazepam 30 mg and 45 mg increased the total duration of sleep compared to brotizolam 0.25 mg. PMID- 17285407 TI - A history of aggression is a risk factor for postoperative confusion in elderly male drinkers. AB - PURPOSE: We investigated the relationship between preoperative psychological state and postoperative confusion in elderly drinkers. METHODS: We studied 81 male patients, ranging in age from 65 to 80 years, who were scheduled to undergo total hip arthroplasty and total knee arthroplasty. The patients were divided into two groups; non-drinkers and patients who drank 25 g or more of alcohol daily. All patients were given a neuropsychological screening evaluation, including a Mini-Mental State test, the Japanese version of the State-Trait Anxiety Inventory (STAI), a depression scale test, and evaluation of a history of aggression and postoperative confusion. RESULTS: Postoperative confusion during the first 72 h after the end of the operation occurred in 7 of the 50 non drinkers (14%) and in 11 of the 31 drinkers (35%) (P = 0.01). There were no significant differences in STAI (state anxiety and trait anxiety), Mini-Mental State, and depression scale scores between the non-drinkers and drinkers, or between patients with and without postoperative confusion. All 8 patients who had a history of aggression developed postoperative confusion. There was no significant difference in the incidence of postoperative confusion between drinkers who did not have a history of aggression and non-drinkers. CONCLUSION: A history of aggression in elderly male drinkers is associated with postoperative confusion. PMID- 17285404 TI - Microtubule-associated proteins in higher plants. AB - A variety of microtubule-associated proteins (MAPs) have been reported in higher plants. Microtubule (MT) polymerization starts from the gamma-tubulin complex (gammaTuC), a component of the MT nucleation site. MAP200/MOR1 and katanin regulate the length of the MT by promoting the dynamic instability of MTs and cutting MTs, respectively. In construction of different MT structures, MTs are bundled or are associated with other components--actin filaments, the plasma membrane, and organelles. The MAP65 family and some of kinesin family are important in bundling MTs. MT plus-end-tracking proteins (+TIPs) including end binding protein 1 (EB1), Arabidopsis thaliana kinesin 5 (ATK5), and SPIRAL 1 (SPR1) localize to the plus end of MTs. It has been suggested that +TIPs are involved in binding of MT to other structures. Phospholipase D (PLD) is a possible candidate responsible for binding of MTs to the plasma membrane. Many candidates have been reported as actin-binding MAPs, for example calponin homology domain (KCH) family kinesin, kinesin-like calmodulin-binding protein (KCBP), and MAP190. RNA distribution and translation depends on MT structures, and several RNA-related MAPs have been reported. This article gives an overview of predicted roles of these MAPs in higher plants. PMID- 17285408 TI - Propofol reduces the incidence of emergence agitation in preschool-aged children as well as in school-aged children: a comparison with sevoflurane. AB - PURPOSE: Young age is considered as one of the factors associated with emergence agitation (EA) following sevoflurane anesthesia. The relationship between EA following propofol anesthesia and young age has not yet been examined. This study was designed to compare the incidence of EA in younger children and older children following either propofol or sevoflurane anesthesia. METHODS: Ninety-six preschool-aged (2-5 years) children and 90 school-aged (6-11 years) children (American Society of Anesthesiologists [ASA] I or II) scheduled to undergo otorhinolaryngological surgery were randomly assigned to receive either propofol or sevoflurane. These children were divided into the following four groups: propofol-preschool (P-pre), sevoflurane-preschool (S-pre), propofol-school (P school), and sevoflurane-school (S-school) groups. Recovery times and incidence of EA were compared among the four groups. RESULTS: We observed that the recovery times were similar in the four groups. After extubation, the incidence of EA in the S-pre group was significantly higher than that in the other groups. After eye opening, the incidence of EA in the S-pre and S-school groups was significantly higher than that in the P-pre or P-school groups. At all recovery times, no difference was observed in the incidence of EA between the P-pre and P-school groups. CONCLUSION: Propofol, in comparison with sevoflurane, resulted in a lower incidence of EA, with no relation to age. PMID- 17285410 TI - Effects of traditional "Juci" (contralateral acupuncture) on orofacial nociceptive behavior in the rat. AB - PURPOSE: "Juci", one of the traditional acupuncture techniques, means contralateral acupuncture; i.e., implanting a needle into an acupoint to treat a given disease or disorder, but on the side of the body opposite to the diseased side. The aim of this study was: (1) to assess acupuncture effects on formalin induced nociceptive behavior in the orofacial region in the rat, and (2) to evaluate the efficacy of Juci in the orofacial formalin test. METHODS: Forty-four adult male Wistar rats were used in the present study. A 1.0% formalin solution (25 microl s.c., diluted in saline) was injected into the right upper lip. The rats were randomly assigned to five groups. (1) The control group (n = 9), which received formalin injection without acupuncture pretreatment; (2) the ipsilateral Ho-ku (see note below) acupuncture group (n = 10); (3) the contralateral Ho-ku acupuncture group (n = 11); (4) the acupuncture plus naloxone group (n = 9), where intraperitoneal naloxone (1.0 mgxkg(-1)) was injected immediately before acupuncture pretreatment; and (5) the sham acupuncture group (n = 5). "Ho-ku" is the term used for the "Large Intestine 4" acupoint, located between the first and second metacarpal bones. RESULTS: The injection of formalin produced the characteristic biphasic behavioral response. Acupuncture significantly inhibited the response in the early and late phases. Naloxone significantly reversed these effects. There were no statistically significant differences between the ipsilateral and Juci acupuncture groups. Sham acupuncture did not exert any significant effect on the formalin-induced behavior. CONCLUSION: Our results showed that the degree of effectiveness of Juci was similar to that of the ipsilateral acupuncture technique. Therefore, the Juci technique is also useful for the treatment of orofacial pain. PMID- 17285409 TI - Pain-relieving effects of intravenous ATP in chronic intractable orofacial pain: an open-label study. AB - PURPOSE: Chronic orofacial pain is often refractory to conventional pain therapies. We conducted an open-label study to determine whether adenosine 5' triphosphate (ATP) could alleviate chronic intractable orofacial pain, and if so, which type of pain could respond to ATP. METHODS: In 8 and 16 patients with non neuropathic and neuropathic intractable orofacial pain, respectively, ATP was intravenously infused at a rate of 100 microgxkg(-1)xmin(-1) over 120 min. The magnitudes of spontaneous pain and brush-evoked allodynia were graded with a visual analog scale (VAS). When a VAS score for spontaneous pain was decreased by 50% or more by ATP, the patient was classified as a responder. RESULTS: The patients could be clearly divided into 10 responders and 14 non-responders. Ten of the 16 patients (62.5%) with neuropathic pain, but none of the 8 patients with non-neuropathic pain, responded to ATP. In particular, all of 8 patients with neuropathic pain following pulpectomy, with or without subsequent tooth extraction, responded to ATP. In the 10 responders, VAS scores for spontaneous pain decreased slowly but progressively during the infusion period, and eventually, ATP reduced the VAS scores for spontaneous pain and allodynia by 82 +/- 15% and 74 +/- 9%, respectively. In these responders, the analgesic and anti allodynic effects of ATP outlasted the infusion period for medians of 7 and 12 h, respectively. CONCLUSION: Intravenous ATP did not relieve non-neuropathic orofacial pain. However, it exerted slowly expressed but long-lasting analgesic and anti-allodynic effects in patients with neuropathic orofacial pain, especially in those suffering from neuropathic pain following pulpectomy and/or tooth extraction. PMID- 17285412 TI - Electrostatic field can preserve red blood cells in stored blood preparations. AB - PURPOSE: During the storage of red blood cell concentrates (CRCs), red blood cells are progressively destroyed and free hemoglobin and potassium concentrations increase. In this study, we focused on an electrostatic field that maintains food freshness without freezing, even at less than the freezing point. We hypothesized that the storage of CRCs under an electrostatic field could keep red blood cells in better condition than conventional storage. METHODS: Each of 15 packs of 2-day-old CRCs, preserved in MAP (mannitol, adenine, glucose, phosphate, and citrate) solution (MAP-CRC) was divided into 4 smaller equal-size packs and stored at 4 degrees C in a newly developed refrigerator that can generate an electrostatic field. Each group was exposed to a 0-, 500-, 1500-, or 3000-volt (V) electric field for 30 days. Concentrations of free hemoglobin, total haptoglobin, sodium (Na), and potassium (K), and the pH, were measured in the supernatant. RESULTS: Haptoglobin was not detected. The Na concentration decreased with time but was significantly lower in the 0-V than in the 500-, 1500 , and 3000-V groups. K and free hemoglobin concentrations increased with time, with significantly higher values in the 0-V than in the 500-, 1500-, and 3000-V groups. The pH decreased in the 500-, 1500-, and 3000-V groups, while it did not change in the 0-V group. The pH decrease was smaller in the 500-V than in the 1500- and 3000-V groups. CONCLUSION: Storing MAP-CRC in an electrostatic field of 500 to 3000 V could decrease hemolysis in the preparation. Considering the lower pH decrease, 500 V might be the field of choice. PMID- 17285411 TI - Effects of propofol and ketamine on ATP-induced contraction of the rat trachea. AB - PURPOSE: ATP causes airway smooth-muscle contraction in patients with asthma and chronic obstructive pulmonary disease. Propofol and ketamine attenuate the airway smooth-muscle contraction induced by histamine and acetylcholine. However, it is not clear whether propofol and ketamine affect the ATP-induced airway smooth muscle contraction. METHODS: We examined the effects of propofol and ketamine on the ATP-induced contraction and ATP-P(2)-purinoceptor binding. RESULTS: Propofol attenuated the ATP-induced contraction in a dose-dependent manner, with a 50% inhibitory concentration of 54 +/- 22 microM. Ketamine at 300 microM attenuated the ATP-induced contraction. In the binding study, propofol attenuated the binding of the P(2)-purinoceptor with [(3)H]-ATP in a dose-dependent manner, while ketamine did not attenuate this binding. CONCLUSION: Propofol attenuates ATP-induced contraction through the inhibition of ATP-P(2)-purinoceptor binding. PMID- 17285413 TI - Effect of positive end-expiratory pressure on inflammatory response in oleic acid induced lung injury and whole-lung lavage-induced lung injury. AB - PURPOSE: The present study investigated the effects of positive end-expiratory pressure (PEEP) on the inflammatory response in two different lung injury models: edematous lung induced by oleic acid (OA); and atelectatic lung induced by whole lung lavage (LAV). METHODS: Japanese white rabbits (n = 28) were allocated to one of the two lung injury (OA or LAV) groups, and each group was treated with intermittent positive pressure ventilation, using zero end-expiratory pressure (ZEEP) or PEEP (1 cm H(2)O above the lower inflection point [LIP]). Thus, the animals were divided into LAV-ZEEP, LAV-PEEP, OA-ZEEP, and OA-PEEP groups. Blood and bronchoalveolar lavage fluid (BALF) were sampled 3 h after ventilatory treatment to analyze interleukin (IL)-8 levels. RESULTS: Pa(O) (2) was significantly decreased after the induction of lung injury, but was significantly higher in the PEEP groups compared to the ZEEP groups for each lung injury. Serum IL-8 levels were elevated in both experimental models. Serum IL-8 levels were significantly lower in LAV-PEEP than in LAV-ZEEP, whereas no difference was noted between OA-PEEP and OA-ZEEP. BALF IL-8 levels were lower in LAV-PEEP than in LAV ZEEP. PEEP above LIP attenuated the elevation of IL-8 in BALF and serum in atelectatic lungs, but did not attenuate these increases in the edematous lungs. CONCLUSION: These results suggest that the protective effects of PEEP on injured lungs may depend on the underlying lung pathology. PMID- 17285414 TI - Efficacy of a heat and moisture exchanger in inhalation anesthesia at two different flow rates. AB - In general anesthesia with endotracheal intubation, a circle system with a heat and moisture exchanger (HME) and a low total flow is often used to prevent hypothermia and to maintain inspired gas humidity. The purpose of the present study was to compare the inspired gas humidity and body temperature, in general anesthesia with or without an HME at two different total flow rates. Eighty patients (American Society of Anesthesiologists [ASA] I or II) scheduled to undergo either orthopedic or head and neck surgery were studied. They were divided into four groups, of 20 patients each: total flow of 2 lxmin(-1) with (group HME2L) or without (group 2L) HME, and a total flow of 4 lxmin(-1) with (group HME4L) or without (group 4L) HME. The relative and absolute humidity and pharyngeal and inspired gas temperatures were measured for 2 h after endotracheal intubation. The relative humidity was not significantly different among groups 2L, HME2L, and HME4L. Group 4L had significantly lower absolute humidity than group 2L. The pharyngeal temperature did not decrease significantly for 2 h in any of the groups. During general anesthesia with a total flow of 2 lxmin(-1) in 2 h, HME might not be necessary, while with a total flow of 4 lxmin(-1), HME could be useful to maintain inspired gas humidity. PMID- 17285415 TI - Pneumocephalus during continuous epidural block. AB - We report a case of pneumocephalus during continuous epidural infusion. A 52-year old malnourished man with rectal cancer had been treated with continuous epidural block for the relief of pain in the left thigh. Eleven days after catheter insertion, a dull, persistent headache occurred in the frontal region, and it worsened gradually. It was precipitated by any head motion and was not relieved by the supine position. A head computed tomography (CT) scan taken 3 days after the onset of the headache revealed about 15 ml of intracranial air and backward compression of the brain. The catheter was removed and the patient maintained bed rest. The headache disappeared 2 days later. It is speculated that the air was sucked in through the space along the epidural catheter. PMID- 17285416 TI - Prolonged cardiac arrest unveiled silent sick sinus syndrome during general and epidural anesthesia. AB - Patients who have silent sick sinus syndrome (SSS) can show various unexpected arrhythmias during surgery. The severity of these bradyarrythmias is affected by anesthetic methods. We report a unique case of a patient with silent SSS who developed 40 s of asystole under combined general and epidural anesthesia. A 40 year-old woman with no apparent cardiac disease underwent abdominal hysterectomy. General anesthesia was induced and maintained with propofol, fentanyl, and vecuronium combined with thoracic epidural anesthesia. During surgery, severe bradycardia, triggered by peritoneal manipulation, occurred, leading to 40 s of asystole. She was diagnosed as having SSS by a postoperative 24-h Holter electrocardiogram. We propose that the possible existence of SSS should be kept in mind even in a patient who shows no abnormalities on routine preoperative examination, especially in those in whom vagomimetic anesthetic methods are used. PMID- 17285417 TI - Pulmonary atelectasis manifested after induction of anesthesia: a contribution of sinobronchial syndrome? AB - A 31-year-old man underwent general anesthesia for sinus surgery. Anesthesia was induced with midazolam and butorphanol, and an endotracheal tube was orally placed with a bronchoscope, due to difficulty with temporomandibular joint opening. Ventilation difficulty and increased peak inspiratory pressure were noticed shortly after tracheal intubation, and bronchoscopy was performed for diagnosis. The bronchi were filled with a clear mucous secretion. Removal of the secretion improved respiration and decreased the peak inspiratory pressure. A chest roentgenogram taken prior to extubation showed right upper lobe atelectasis. A diagnosis of sinobronchial syndrome was made postoperatively. The etiology of the acutely developed atelectasis was unclear. However, the latent syndrome may have induced excessive airway secretion with stimuli such as endotracheal intubation. PMID- 17285418 TI - Sedation for endoscopic retrograde cholangiopancreatography (ERCP) in a pregnant patient. AB - Anesthesiology management of endoscopic retrograde cholangiopancreatography (ERCP) in the twenty-first week of pregnancy of a woman patient is reported. The patient gave birth to a healthy male baby at 40 weeks of gestation. PMID- 17285419 TI - Anesthetic management of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) during laparotomy. AB - A 53-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) underwent a gastrectomy. We administered bicarbonated Ringer's solution, which has a physiological concentration of bicarbonate. The level of serum lactate did not increase significantly, and metabolic acidosis did not occur throughout surgery or for 3 h after surgery. Aggressive warming was needed to maintain normothermia, presumably because the mitochondrial respiratory chain, which is responsible for thermogenesis, is impaired in MELAS patients. It is important to maintain normothermia in MELAS patients in order to avoid further mitochondrial metabolic depression. PMID- 17285420 TI - Bilateral tension pneumothoraces following jet ventilation via an airway exchange catheter. AB - We report a case involving a 55-year-old man who had a recent resection of tracheal carcinoma and tracheal reanastomosis. He subsequently developed tracheomalacia and anastomotic dehiscence requiring airway stenting via an armored endotracheal tube (ETT). Placement of the armored ETT was technically difficult. It required insertion of an airway exchange catheter through the tracheal stoma to oxygenate, ventilate, and serve as a guide for ETT placement through the tracheotomy and across the dehiscence. During transtracheal jet ventilation our patient developed bilateral tension pneumothoraces requiring cardiopulmonary resuscitation and chest tube placement. The patient was quickly recovered, stabilized, and later discharged after a prolonged intensive care unit (ICU) course. We review the recommendations for jet ventilation via airway exchange catheters, common problems during this technique, and potential methods for avoiding these problems. The risk of barotrauma and pneumothoraces during jet ventilation via an airway exchange catheter should be kept in mind. PMID- 17285422 TI - Use of a wire-guided cannula for radial arterial cannulation. AB - We compared the success rates of arterial cannulation with a wire-guided cannula (WGC) and the direct technique with a conventional non-wire-guided cannula (non WGC). A total of 100 adult patients requiring an arterial line in the operating room were assigned randomly to undergo radial arterial cannulation either with the WGC or with the non-WGC. No significant difference in success rates and insertion times could be demonstrated between the WGC and the non-WGC (78.4% vs 67.3% and 22.6 +/- 13.2 s vs 23.0 +/- 19.3 s, respectively). Among the less experienced operators, insertion time was shorter with the WGC than with the non WGC (27.7 +/- 11.9 s vs 39.8 +/- 20.4 s; P < 0.05), although the success rate was similar for the two types of cannula. Patient characteristics did not affect either the success rates or the insertion times for the two types of cannula. In conclusion, we have confirmed that the success rates of radial arterial cannulation for patients whose physical status is relatively good were similar with the use of the WGC and the non-WGC. PMID- 17285423 TI - Effects of magnesium sulfate on neuromuscular function and spontaneous breathing during sevoflurane and spinal anesthesia. AB - The purpose of the present study was to determine the effects of magnesium sulfate (MgSO(4)) on the neuromuscular function and spontaneous breathing of patients under sevoflurane and spinal anesthesia. Twenty-two patients with a history of arrhythmia undergoing elective knee surgery were randomly assigned to two groups: group M (n = 11), administered with MgSO(4) 40 mg.kg(-1), and group S (n = 11), administered with saline. A combination of spinal anesthesia with 2% sevoflurane inhalation was applied to all patients under spontaneous breathing. Tidal volume (VT: ), respiratory rate (RR) and end-tidal carbon dioxide (ET(CO) (2)) were measured before the MgSO(4) or saline injection and measurements were repeated at 5, 15, 30, and 45 min after the injection. Neuromuscular function was continuously monitored with an acceleromyograph to record the acceleration of the adductor pollicis by stimulating the ulnar nerve at a frequency of 0.1 Hz. The VT: , RR, and ET(CO) (2) showed little change in either group, and there was no significant difference between, the groups. The single-twitch response showed significant differences between the two groups (P = 0.0006). The present study indicated that the MgSO(4) had a minimal effect on spontaneous breathing in patients undergoing sevoflurane and spinal anaesthesia, but that it attenuated the safety margin of neuromuscular function. PMID- 17285421 TI - Undiagnosed catecholamine-secreting paraganglioma and coexisting carcinoid in a patient with MH susceptibility: an unusual anesthetic challenge. AB - The management of a patient with two undiagnosed neuroendocrine tumors and possible malignant hyperthermia (MH) susceptibility poses a unique challenge to the anesthesiologist. We describe a total intravenous anesthetic including an alpha 2-agonist infusion combined with epidurally administered bupivacaine for intra- and postoperative pain management. Alpha 2-agonists may offer improved intraoperative hemodynamic management in patients with catecholamine-secreting tumors and reduce the total dose needed for intravenous anesthetics such as propofol. The latter mechanism may be useful to avert the risk of the propofol infusion syndrome occurring as a consequence of a high cumulative dose following its prolonged administration. PMID- 17285424 TI - The outcome of preterm neonates with intraventricular hemorrhage delivered with intravenous meperidine or epidural analgesia. AB - We aimed to study, retrospectively, the neonatal outcome of 45 preterm neonates with intraventricular hemorrhage (IVH) who were delivered vaginally with intravenous meperidine (n = 23) or epidural analgesia (n = 22). Neonates in the epidural group had a better outcome in terms of a first-minute Apgar score of 7 or less, in 31% vs 69% (P = 0.001); 5-min Apgar score of 7 or less, in 18% vs 82% (P = 0.003); a lower incidence of respiratory distress syndrome (RDS; 23% vs 30%; P = 0.03); a lower dopamine requirement during the first neonatal week (13% vs 72%; P = 0.01); and a higher survival rate (91% vs 58%, respectively; P = 0.008). It is concluded that preterm neonates with IVH had a better outcome when delivered to mothers receiving epidural analgesia as compared to those receiving intravenous meperidine. PMID- 17285425 TI - Comparison of the effects of fentanyl and remifentanil on splanchnic tissue perfusion during cardiac surgery. AB - The purpose of this study was to compare the effects of fentanyl and remifentanil on splanchnic perfusion during coronary artery bypass graft (CABG) surgery. Fifty patients were randomized to receive either fentanyl (10 microgxkg(-1) at induction and 5 microgxkg(-1)xh(-1) infusion for maintenance) or remifentanil (3 microgxkg(-1) at induction and 1 microgxkg(-1)xmin(-1) infusion for maintenance). Patients in both groups were comparable with regard to demographics. Intraoperative volume management and inotropic therapy were similiar in both groups. Regarding heart rate, there were no significant differences between the groups at any measurement time (P > 0.05). Compared to the fentanyl group, the remifentanil group showed a significant decrease in mean arterial pressure during induction. Also, the gastric intramucosal CO(2) pressure (Pg(CO) (2)) and the P(CO) (2)-gap, defined as the difference between Pg(CO) (2) and Pa(CO) (2), were significantly increased and the gastric mucosal pH (pHi) was significantly decreased in the remifentanil group in the postinduction period (P < 0.05). However, there were no statistically significant differences in respiratory data at any time between the two groups (P > 0.05). Both fentanyl and remifentanil seemed to be effective and well tolerated in this CABG population. Episodes of hypotension and transient reduction in splanchnic perfusion were more common in patients treated with remifentanil when compared to those receiving the fentanyl opioid regimen. PMID- 17285426 TI - Application of nasal flexible laryngeal mask airway in anesthesia for oral surgery. AB - The laryngeal mask airway has been used increasingly in clinics but is seldom applied in anesthesia for oral surgery, as the mask occupies the middle of the mouth and tends to obstruct the surgical field. Here, we report the successful placement and usage of a nasal flexible laryngeal mask airway (FLMA) in an oral surgical procedure. Fifteen patients undergoing dental procedures under general anesthesia were studied. We clinically applied a previously reported method for inserting an FLMA with some modifications. There was no significant bleeding from the intubated nostril in any of the patients. None of the patients complained of sore throat, coughing, hoarseness, or any discomfort in the nose. Although we anticipate that further refinements of the technique may be possible and that the safety of this method using a nasal FLMA needs to be assessed in a greater number of patients, in this preliminary study we provide a proof-of-principle demonstration of the efficacy of nasal LMA ventilation as a method of airway management for oral surgery. PMID- 17285427 TI - Not all placebos are the same: a debate on the ethics of placebo use in clinical trials versus clinical practice. PMID- 17285428 TI - Recombinant activated factor VII and epsilon aminocaproic acid treatment of a patient with Glanzmann's thrombasthenia for nasal polipectomy. PMID- 17285429 TI - Effect of 2.5% sevoflurane, at PaCO2 30 mmHg for epileptic focus resection, on hemodynamics and hepatic and renal functions. PMID- 17285430 TI - Comparison of continuous intraarterial blood gas analysis and transcutaneous monitoring to measure oxygen partial pressure during one-lung ventilation. PMID- 17285431 TI - Endoscopic retrograde cholangiopancreatography: with or without anesthesia? PMID- 17285432 TI - Epidural anesthetic management using ropivacaine in a parturient with multi minicore disease and susceptibility to malignant hyperthermia. PMID- 17285438 TI - Early sign of atherosclerosis in slow coronary flow and relationship with angiotensin-converting enzyme I/D polymorphism. AB - Increase in carotid artery intima-media thickness (IMT) is an early sign of atherosclerosis. Slow coronary flow (SCF) is characterized by delay of opacification of coronary arteries in coronary angiography in the absence of any evident obstructive lesion, but its etiopathogenesis remains unclear. Genes that regulate the renin angiotensin system also play a role in developing cardiovascular system disorders. The presence of deletion (D) allele in angiotensin converting enzyme (ACE) gene polymorphism is associated with coronary artery disease. The aim of this study was to investigate the carotid artery IMT measurement, as an early sign of atherosclerosis, in patients with SCF and without SCF and also to assess the effect of the renin-angiotensin gene system on carotid IMT. Forty-four patients with angiographically proven SCF and 44 cases with normal coronary flow (NCF) pattern with similar risk profile were enrolled in the study. Coronary flow patterns of the cases were determined by thrombolysis in myocardial infarction (TIMI) frame count method. Intima-media thickness was measured by recording ultrasonographic images of both the left and right common carotid artery with a 12-MHz linear array transducer. ACE I/D polymorphism and Angiotensin II tip 1 receptor (AT1R) A/C gene polymorphism were determined by polymerase chain reaction (PCR) amplification. Demographic characteristics and coronary artery disease risk factors of SCF and NCF groups were similar. Mean TIMI frame count and carotid IMT (mm) were significantly higher in the SCF group than controls (45.9 +/- 12 vs 23.3 +/- 3.7, P = 0.0001; 0.75 +/- 0.08 vs 0.69 +/- 0.06, P = 0.0001, respectively). Mean TIMI frame count was positively correlated with IMT of carotid artery in correlation analysis (r = 0.45, P = 0.0001). When analyzed in regard to ACE genotype in all subjects, IMT values were statistically different (0.78 +/- 0.06 for DD genotype, 0.72 +/- 0.05 for ID genotype, and 0.64 +/- 0.06 for II genotype, P = 0.0001). This difference remained significant in subgroup analyses for each genotype. No association could be observed between the AT1R A/C(1166) polymorphism and IMT of carotid artery measurement (P > 0.05). Lack of association was still observed with analysis carried out when genotype effect was assumed to be inherited as additive (CC versus AA versus AC) or dominant (AA versus AC+CC). Increased IMT in patients with SCF shows that subclinical atherosclerosis may play role in this phenomenon. This increase was most marked in the presence of D allele of ACE genotype, which is associated with vascular hypertrophy. PMID- 17285439 TI - Sex-related characteristics in hospitalized patients with acute coronary syndromes--the Greek Study of Acute Coronary Syndromes (GREECS). AB - We studied the sex-specific distribution of various factors in hospitalized patients who presented with acute coronary syndromes (ACS), as well as the annual incidence and the in-hospital and short-term outcomes in males and females. A sample of six hospitals located in Greek urban and rural regions was selected. In these hospitals we recorded almost all nonfatal admissions with a first event of ACS, from October 2003 to September 2004. Sociodemographic, clinical, dietary, and other lifestyle characteristics were recorded. A total of 2,172 patients were included in the study (1,649, 76% male and 523, 24% female). The annual incidence rate was almost three times higher in males than in females (34 per 10,000 males and 10.9 per 10,000 females). The highest frequency of events was observed in winter, in both sexes. Females had higher in-hospital mortality rate as compared to males (5.7% vs 3.2%, P = 0.007), while the 30-day mortality and rehospitalization rate was 17% in male and 16% in female patients. The most common discharged diagnosis for males was Q-wave myocardial infraction (35%), while females were more likely to suffer from unstable angina (42%). Females were older than males, waited longer between seeking and receiving medical advice, and were more likely to have a history of hypertension, obesity, and diabetes mellitus as compared to males. On the other hand, males were more likely to be smokers, to follow a more typical Mediterranean diet, and to be more physically active (P < 0.05). We revealed a sex-related difference in the profile of clinical characteristics and other cardiovascular risk factors in hospitalized patients for ACS. PMID- 17285441 TI - Impact of volume status on the incidence of atrial fibrillation following aortic arch repair. AB - We evaluated the volume status of patients undergoing aortic arch repair to determine the impact of fluid balance on risk of postoperative atrial fibrillation (AF). From 1993, 445 patients who underwent total aortic arch repair were enrolled in this study. Patients who had AF preoperatively or died within the 10th postoperative day (POD) were excluded. Volumes administered (input) and eliminated (output) through all routes were recorded, and fluid balance (input minus output) was calculated intraoperatively, on the day of surgery, and PODs 1 2. The incidence of new onset of AF was 53.9% (240/445). Total input on POD 1 was greater in patients developing AF than in those not developing it (3,372 +/- 90 vs 3,012 +/- 79; P = 0.0036), as was net fluid balance on POD 1 as well (-806 +/- 84 vs -558 +/- 90; P = 0.050). Blood transfusion volume was greater in patients developing AF than in those not developing it on POD 1 (1,285 +/- 89 vs 927 +/- 74; P = 0.003) and POD 2 (405 +/- 53 vs 227 +/- 47; P = 0.015). Increased input volume and net fluid balance on POD 1 are associated with an increased risk of postoperative AF in patients undergoing aortic arch surgery. PMID- 17285440 TI - Persistent symptomatic pleural effusion following coronary bypass surgery: clinical and histologic features, and treatment. AB - Pleural effusions following coronary artery bypass grafting (CABG) have been reported in 65%-89% of the cases. The majority of pleural effusions are left sided, of little significance, and resolve spontaneously. However, a few pleural effusions require specific therapeutics. We report clinical and pleural histologic features of three patients who had persistent post-CABG pleural effusions and underwent video-assisted thoracic surgery (VATS). These patients were studied because they had a persistent pleural effusion within the first 2 months after CABG without other identifiable causes. All patients underwent VATS for investigation and management of persistent pleural effusions. Three patients with a mean age of 63.6 +/- 8.5 years were studied. The pleural effusion developed 38 +/- 11.3 days after CABG (range: 22-46). The median period from CABG to VATS was 80 +/- 21.6 days (range: 50-100). In all cases, the pleural effusion was large, and predominated on the left side. Pleural effusions were characterized by an exudative (n = 2) or transudative (n = 1) fluid with lymphocytosis. Histologic examination of pleural biopsies showed a follicular lymphoid hyperplasia involving the pleural serosa and a non-necrotizing granulomatous reaction with a mild inflammatory infiltrate. All patients underwent VATS with intrapleural injection of sclerosing agents. Video-assisted thoracic surgery talc pleurodesis led to symptomatic and radiologic improvement in all patients with a mean follow-up of 16.7 +/- 4.5 months. No recurrence of pleural effusion has been observed in any patient. Large pleural effusions can develop in a small proportion of patients after CABG. The mechanism of pleural effusion remains unclear. Video-assisted thoracic surgery could play a significant role in the management of pleural effusion developing after CABG. PMID- 17285443 TI - Elevated carbohydrate antigen 125 levels in hypertrophic cardiomyopathy patients with heart failure. AB - Carbohydrate antigen 125 (CA 125), known as a tumor marker for ovarian cancer, has been reported to increase and relate to severity in heart failure patients with systolic dysfunction. Hypertrophic cardiomyopathy (HCM) has a wide clinical spectrum that often includes heart failure symptoms. The aim of this study was to evaluate the role of CA 125 in HCM patients, its relation to severity of symptoms, and degree of diastolic dysfunction. CA 125 blood levels were determined in 32 HCM patients (21 male; age 51.3 +/- 18.4 years) and in 30 healthy volunteers (19 male; age 49.6 +/- 16.1 years). Echocardiographic examinations were performed in all patients. The results were grouped according to clinical status (New York Heart Association class) of the patients. The mean serum level of CA 125 was 14.6 +/- 23.8 U/ml in the study group and 7.6 +/- 4.8 U/ml in the control group. There was no significant difference between the groups (P = 0.12). CA 125 levels increased as the New York Heart Association functional class increased (class I/II: 6.2 +/- 2.4 U/ml; class III: 30.6 +/- 36.4 U/ml; P < 0.001). The mean CA 125 level in functional class III patients (30.6 +/- 36.4 U/ml) was significantly higher than that of the control group (7.6 +/- 4.8 U/ml) (P < 0.001) and the functional class I/II group (6.2 +/- 2.4 U/ml) (P < 0.001). There was a significant difference over all three diastolic dysfunction groups with respect to CA 125 levels (4.9 +/- 1.3 U/ml in impaired relaxation group, 11.8 +/- 6.9 U/ml in pseudonormal group, and 52.6 +/- 45.6 U/ml in restrictive filling group; P < 0.0001). Serum CA 125 is related to the clinical severity of HCM. Whether CA 125 has a specific biological role in HCM requires further investigation. PMID- 17285442 TI - Significance of transient left ventricular wall thickening in acute lymphocytic myocarditis. AB - Transient left ventricular (LV) wall thickening is observed in patients with acute lymphocytic myocarditis. The present study was undertaken to clarify the significance of transient LV wall thickening in patients with this disease. The subjects comprised 25 patients with acute lymphocytic myocarditis. Echocardiography was used to measure the thickness of the interventricular septum (IVS) and the LV posterior wall (PW) at four time points after myocarditis onset- namely, on days 1-3, 6-8, 13-15, and 28-30--to clarify the timing and frequency of wall thickening. The 25 patients were divided into a fulminant myocarditis group (n = 14) and a nonfulminant myocarditis group (n = 11), and the relationship between LV wall thickening and myocarditis severity was investigated. Left ventricular wall thickening was greatest on days 1-3 after myocarditis onset (IVS: 13.3 +/- 3.2 mm; PW: 12.1 +/- 2.6 mm), with this finding being noted in 14 of the 25 cases (56%). By days 6-8, the thickness of IVS had virtually normalized to 10.6 +/- 1.6 mm (P < 0.0001) and that of PW to 10.2 +/- 1.4 mm (P = 0.0006). The thickness of the IVS and PW on days 1-3 after myocarditis onset were 14.6 +/- 3.7 and 13.0 +/- 2.9 mm, respectively, in the fulminant group (P = 0.014), and 11.5 +/- 0.9 and 10.9 +/- 1.4 mm, respectively, in the nonfulminant group (P = 0.039). In lymphocytic myocarditis, LV wall thickening is greatest on days 1-3 after myocarditis onset and improves to near normal by days 6-8. Such transient LV wall thickening occurs in approximately 50% of cases. Left ventricular wall thickening was more marked in the fulminant compared with the nonfulminant group. PMID- 17285444 TI - Developmental changes in the expression of voltage-gated potassium channels in the ductus arteriosus of the fetal rat. AB - Oxygen-sensitive, voltage-gated potassium channels (Kv) may contribute to the determination of the membrane potential in smooth muscle cells of the ductus arteriosus (DA), and thus to regulation of contractile tone in response to oxygen. Developmental changes in Kv during gestation may be related to closure of the DA after birth. This study investigated developmental changes in the expression of Kv in the DA and compared it with that of the pulmonary artery (PA) and the aorta (Ao). The DA, PA, and Ao were isolated from fetal rats at days 19 and 21 of gestation (term: 21.5 days). The expression of Kv1.2, Kv1.5, Kv2.1, and Kv3.1, putative oxygen-sensitive Kv channels that open in response to oxygen, was evaluated at both the mRNA and protein levels, using quantitative real-time polymerase chain reaction and immunohistochemistry. In the Kv family studied, Kv1.5 mRNA was expressed most abundantly in the DA, PA, and Ao in both day-19 and day-21 fetuses. Although the expression levels of Kv1.2, Kv1.5, Kv2.1, and Kv3.1 did not change much with development in the PA and Ao, in the DA they decreased with development. The decrease in the expression of Kv channels may enhance DA closure after birth by eliminating the opening of Kv channels when oxygen increases. PMID- 17285445 TI - RNA interference targeting embryonic myosin heavy chain isoform inhibited mRNA expressions of phenotype markers in rabbit cultured vascular smooth muscle cells. AB - To investigate whether the knockdown of SMemb gene expression induces phenotypic modulation of vascular smooth muscle (VSM) cells toward a contractile type, we constructed a siRNA targeting the 3' untranslated region (UTR) of SMemb gene (SMemb-siRNA). The SMemb-siRNA was introduced into cultured rabbit VSM cells for 48 h at 37 degrees C by the lipofection method. The mRNA expressions were estimated by comparative reverse transcription-polymerase chain reaction (RT PCR). SMemb-siRNA significantly decreased the ratio of SMemb to glyceraldehyde-3 phosphate dehydrogenase (GAPDH) mRNA expression in a dose-dependent manner (P < 0.01): 0 nM, 0.90 +/- 0.08; 100 nM, 0.43 +/- 0.07. Immunofluorescence and immunoblot analyses demonstrated that SMemb-siRNA markedly decreased SMemb protein expression to 56% +/- 7.8% (P < 0.01). Other MHC isoform (SM1 and SM2) mRNA expressions were not changed. The relative mRNA expressions of other phenotype markers (plasminogen activator inhibitor (PAI)-1 and beta-actin) were significantly decreased by SMemb-siRNA to 71% +/- 7.5% and 61% +/- 7.5%, respectively (P < 0.01). Expression of smooth muscle (SM) alpha-actin protein and cell proliferation was not changed by SMemb-siRNA. Thus, SMemb gene might be involved in the transcription of PAI-1 and beta-actin, but not involved in SM alpha-actin and cell proliferation in cultured VSM. PMID- 17285446 TI - Successful high-dose intravenous immunoglobulin therapy for a patient with fulminant myocarditis. AB - A 45-year-old man developed fulminant myocarditis for which ventricular assist devices (intra-aortic balloon pumping and percutaneous cardiopulmonary support) were required for hemodynamic support. Echocardiography showed left ventricular akinesis and, since no improvement was noted on the following day, immunoglobulin (70 g/day for 2 days) was added to the therapy. The left ventricular ejection fraction increased to 25% and 40% at 12 and 36 h, respectively, representing a marked improvement in wall motion within a very short period. An endomyocardial biopsy specimen revealed focal lymphomononuclear infiltrate with adjacent myocytolysis, and acute lymphocytic myocarditis was diagnosed. Two days after administration of immunoglobulin, the serum level of interleukin-6 decreased rapidly from 180 to 5.9 pg/ml. In this patient, cardiac function improved immediately after immunoglobulin administration, suggesting the usefulness of this therapy. Three years after the diagnosis the patient is in good health, with steady normal left ventricular ejection fraction. We conclude that there are cases of acute myocarditis in which high-dose intravenous immunoglobulin therapy is effective. PMID- 17285447 TI - Primary cardiac lymphoma presenting as atrial flutter and total heart block. AB - Primary cardiac lymphoma is extremely rare. We present the case of a 70-year-old man with primary cardiac lymphoma involving interatrial septum, presenting as atrial flutter and total heart block. The diagnosis was obtained by echocardiography-guided transvenous endocardial biopsy which revealed diffuse large B-cell non-Hodgkin's lymphoma, CD 20+. After six courses of immunochemotherapy the patient achieved complete remission. After 2 months he developed a series of epileptic attacks. Intracerebral lymphoma extension was diagnosed. Two cycles of high-dose methotrexate and cranial irradiation were applied, resulting in a second complete remission. PMID- 17285448 TI - Atrial tachycardia originating at the tricuspid annulus. AB - We report a patient with re-entrant atrial tachycardia that originated at the inferolateral tricuspid annulus. Single atrial extra-stimulation reproducibly induced the atrial tachycardia with an inverse relationship between the coupling interval of extra-stimulation and the return cycle of the first tachycardia beat. A real-time three-dimensional electroanatomical mapping showed focal atrial activation spreading semi-radially from the tricuspid annulus. The tachycardia was successfully eliminated by radiofrequency ablation at the earliest atrial activation site, preceding by 27 ms the arbitrary determined onset of surface P wave. An accelerated atrial rhythm with similar P-wave morphology to that of the tachycardia was observed at the successful ablation site during radiofrequency application. The mechanism of this tachycardia seems to be due to re-entry originating in or around the possible accessory atrioventricular node without ventricular connection. PMID- 17285449 TI - A case of takotsubo cardiomyopathy associated with epileptic seizure: reversible left ventricular wall motion abnormality and ST-segment elevation. AB - A 59-year-old woman was admitted for consciousness disturbance. She had a history of endocranial operation for astrocytoma. Her electrocardiogram showed ST-segment elevation indicative of acute myocardial infarction. Emergency coronary angiography showed normal coronary arteries, whereas left ventriculography showed extensive severe hypokinesis in the anteroseptal and apical segments. Electroencephalography showed slow sharp wave activity from the left frontal lobe to the temporal lobe, and she was diagnosed as having status epilepticus. This is a rare case of takotsubo cardiomyopathy associated with epileptic seizure. Acute myocardial ischemia caused by impaired coronary microcirculation induced by abnormal catecholamine release is a possible cause of cardiac wall motion abnormality, as in our case. PMID- 17285451 TI - American Society of Hematology--48th Annual Meeting and Exposition. 9-12 December 2006, Orlando, FL, USA. PMID- 17285450 TI - Warfarin-induced skin necrosis after open heart surgery due to protein S and C deficiency. AB - Warfarin-induced skin necrosis is the rare but potentially devastating complication of anticoagulant therapy and commonly occurs in previously undetected C- and S-protein deficient patients. Because routine preoperative examination does not include protein C and S level measurement, detection of these patients preoperatively is generally not possible, which increases the risk of occurrence of this important complication. In this report we present and discuss such a patient, who died from warfarin-induced skin necrosis after coronary artery bypass surgery. PMID- 17285452 TI - American Society of Hematology--48th Annual Meeting and Exposition. Updates on hematological therapies. 9-12 December 2006 Orlando, FL, USA. PMID- 17285453 TI - American Society of Hematology--48th Annual Meeting and Exposition. The Factor Xa target, and disorders of platelet number and function. 9-12 December 2006 Orlando, FL, USA. PMID- 17285454 TI - American Society of Hematology--48th Annual Meeting and Exposition. Therapeutic approaches for hematological cancers. 9-12 December 2006 Orlando, FL, USA. PMID- 17285455 TI - American Society of Hematology--48th Annual Meeting and Exposition. Treatments for leukemia and lymphoma. 9-12 December 2006 Orlando, FL, USA. PMID- 17285456 TI - American Society of Hematology--48th Annual Meeting and Exposition. Updates on therapies. 9-12 December 2006 Orlando, FL, USA. PMID- 17285457 TI - American Society of Tropical Medicine and Hygiene--55th Annual Meeting. 12-16 November 2006, Atlanta, GA, USA. PMID- 17285458 TI - American Society of Tropical Medicine and Hygiene--55th Annual Meeting. Vaccine development against flaviviruses. 12-16 November 2006, Atlanta, GA, USA. PMID- 17285459 TI - New Agents in Clinical Oncology. 24 November 2006, London, UK. PMID- 17285460 TI - Nociception: Taking the Pain out of Drug Discovery. 28 November 2006, London, UK. PMID- 17285461 TI - Global Imaging Summit 2006: Optimizing Imaging Techniques in Preclinical and Clinical Drug Development. 5-6 December 2006, Zurich, Switzerland. PMID- 17285462 TI - From Genomes to Protective Antigens--Designing Vaccines (GPADV 2006). Designing improved and novel vaccines in the future. 15-17 November 2006, Prague, Czech Republic. PMID- 17285463 TI - Structure-based drug design of new leads for phosphatase research. AB - Biological targets that are challenging to pursue for medicinal chemists, such as the protein phosphatases, require creative and innovative approaches for identifying and optimizing previously unknown classes of inhibitors. To achieve these lofty objectives, medicinal chemists must utilize the latest computational, structural biology, synthetic and analytical technologies in the drug development process. The iterative use of structure-based drug design often plays a key role, as illustrated by the independent discoveries of two research groups involving the identification and optimization of protein tyrosine phosphatase 1B inhibitors that have novel heterocyclic phosphotyrosine mimetics. The newly designed pharmacophore provides a promising chemical lead for phosphatase drug discovery and a valuable chemical tool for phosphatase research in general. PMID- 17285464 TI - The interaction between intellectual property and drug regulatory systems: global perspectives. AB - Regulatory compliance in the development, production and sale of new drugs accounts for the largest single expense in bringing a drug product to market. To justify developmental and regulatory compliance costs, drug innovators turn to the intellectual property (IP) system to provide a means for securing returns on investment. Because the drug regulatory system in most countries operates in isolation of the IP system, one of the greatest challenges facing the pharmaceutical industry is the extent to which IP rights can be managed against an independent drug regulatory system. Many regulatory bodies in developed countries have sought to ensure a compromise between the rights of generic companies and IP owners by including safeguards in the regulatory framework, such as patent linking and data protection; however, these efforts are yet to be applied in some of the biggest potential drug markets in emerging economies. PMID- 17285465 TI - Drug evaluation: (R)-flurbiprofen--an enantiomer of flurbiprofen for the treatment of Alzheimer's disease. AB - (R)-flurbiprofen, the R-enantiomer of racemic flurbiprofen, is undergoing development by Myriad Genetics Inc, under license from Encore Pharmaceuticals Inc, for the potential treatment of Alzheimer's disease (AD). Devoid of any direct cyclooxygenase inhibition, which is associated with the more toxic S enantiomer of flurbiprofen, (R)-flurbiprofen appears to modulate gamma-secretase, the enzyme that cleaves the C-terminal portion of the malignant Abeta(1-42) peptide out of amyloid precursor protein. In murine models of AD, (R) flurbiprofen lowered brain levels of Abeta(1-42), and chronic dosing reduced brain amyloid pathology and prevented defects in learning and memory. In a phase II clinical trial in AD, (R)-flurbiprofen was determined to be most effective in a subset of patients who had high blood concentrations of the drug (> 75 microg/ml). These patients demonstrated a benefit in cognitive and behavioral performance that ranged from 36 to 48%, and statistical significance was achieved for two out of three trial endpoints. Compared with placebo, (R)-flurbiprofen also significantly reduced the incidence of psychiatric problems and the average time to a first psychiatric incidence. (R)-flurbiprofen has been generally well tolerated at high doses in clinical trials. Two pivotal phase III clinical trials in AD are underway in more than 2400 patients. The compound had also been under development for the treatment of prostate cancer; however, this indication was discontinued after disappointing phase IIa trial results. PMID- 17285466 TI - Changes of myocardial function after combined coronary revascularization and mitral valve downsizing in patients with ischemic mitral regurgitation and advanced cardiomyopathy. AB - OBJECTIVE: At present not much data is available on changes in myocardial function after combined coronary artery bypass grafting (CABG) and downsizing of the mitral valve (MV) by restrictive prosthetic ring annuloplasty in patients with chronic ischemic mitral regurgitation (IMR) and advanced cardiomyopathy. METHODS: 63 patients with coronary artery disease, chronic IMR grade 3 - 4+, ischemic cardiomyopathy and reduced left ventricular (LV) function (LV ejection fraction [LVEF] of 30 +/- 9 %; range 12 - 45 %) underwent combined CABG and MV downsizing. Clinical follow-up and serial echocardiographic studies were performed to assess survival, New York Heart Association (NYHA) class, mitral regurgitation (MR), leaflet coaptation height (LCH), left atrial (LA) and LV end systolic/end-diastolic dimensions/volumes and volume indices (LVESD, -EDD; LVESV, -EDV; LVESVI, -EDVI), fractional shortening (FS) and LVEF to evaluate the changes in myocardial function after surgery. RESULTS: Early mortality (< 30 days) was 1.6 %, survival at follow-up was 95 % (3 +/- 1 months) and 83 % (2 +/- 1 years), respectively. Functional class improved significantly after surgery; recurrence of relevant MR was absent in all patients. In general, LA/LV dimensions/volumes and volume indices, FS and LVEF improved significantly, even in patients with already severely reduced preoperative LV function (LVEF /= 6). AB - OBJECTIVE: The aim of this study was to review the results of off-pump (OPCAB) versus conventional on-pump coronary artery bypass surgery (CCAB) in high-risk patients. METHODS: In a cohort of patients with an additive EuroSCORE >/= 6, 67 underwent OPCAB and 112 underwent CCAB. RESULTS: Thirty-day postoperative death and stroke rates were 7.5 % and 6.0 % for the OPCAB group, and 5.4 % ( P = 0.75) and 8.0 % ( P = 0.77) for the CCAB group, respectively. No significant differences were observed for other major outcome endpoints other than cardiac troponin I (OPCAB: 117 +/- 428 ng/ml vs. CCAB: 58 +/- 99 ng/ml, P = 0.028), a result which was probably due to preoperative massive myocardial infarction in two very high-risk patients who underwent OPCAB. A similar outcome was also observed among propensity score-matched pairs. Congestive heart failure ( P = 0.006, OR: 6.366, 95 % CI: 1.682 - 24.093) and baseline cardiac index ( P = 0.018, OR: 0.171, 95 % CI: 0.040 - 0.735) were independent predictors of 30-day postoperative mortality. CONCLUSIONS: OPCAB can be safely performed in high-risk patients with results as satisfactory as those achieved with CCAB. PMID- 17285469 TI - Actual management of patients with familial ascending aortic aneurysms and type-A aortic dissections. AB - BACKGROUND: There are few families with the diagnosis of ascending aortic aneurysm and acute type-A aortic dissection inherited as an autosomal-dominant disorder in the absence of a known genetic syndrome. METHODS: We investigated a family with 26 members in whom ascending aortic aneurysms and acute type-A aortic dissections occurred over three generations. Examinations were performed to identify family members at specific risk. RESULTS: Six members presented with acute type-A aortic dissections and three relatives had ascending aortic aneurysms. Clinical examinations showed no characteristics of a known genetic syndrome. Molecular genetic analysis revealed no mutations known to cause a form of autosomal-dominant inherited aortic disease. CONCLUSION: Adequate diagnostic measures are mandatory in families with ascending aortic aneurysms or type-A aortic dissections to identify or exclude family members at risk for aortic diseases. Even in the absence of identifiable mutations causing isolated aortic aneurysms or aortic dissections, we recommend standardised examinations of all first-degree relatives of affected families. An indication for prophylactic aortic root replacement should be considered for patients at risk. PMID- 17285470 TI - Granulocyte-macrophage colony-stimulating factor (GM-CSF) restores decreased monocyte HLA-DR expression after cardiopulmonary bypass. AB - OBJECTIVES: Cardiopulmonary bypass (CPB) is associated with a disturbed immune response, e.g., impaired HLA-DR expression on monocytes and the release of pro- and anti-inflammatory cytokines. Cytokine release plays a role in the pathogenesis of postoperative systemic inflammatory response syndrome (SIRS) and immune system deterioration, e.g., impaired monocyte and polymorphonuclear neutrophil (PMN) function, factors that ultimately lead to an increased susceptibility to infections. To gain a further understanding, we investigated HLA-DR expression on monocytes and on B- and T-lymphocytes. In addition, we investigated the IN VITRO effect of the immunostimulating hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) on HLA-DR expression of these cell types. Neither HLA-DR expression on B- and T-lymphocytes nor the effects of GM-CSF in cardiac surgical patients have been studied before. METHODS: In 16 patients undergoing elective cardiac surgery with CPB, counts of circulating leukocyte subsets as well as HLA-DR expression on monocytes, B- and T lymphocytes were measured by flow cytometry before, immediately after CPB, and on the 2nd and 10th postoperative days. Treatment with GM-CSF was performed IN VITRO in whole blood cultures with 100 ng/ml recombinant human GM-CSF for 20 h. RESULTS: Monocyte HLA-DR expression was attenuated immediately after CPB (125 +/- 4 mean channel fluorescence [MCF] vs. 143 +/- 2 MCF preoperatively, mean +/- SEM, P < 0.001). HLA-DR expression further decreased on the 2nd day after CPB and did not normalize until the 10th day after the operation. In contrast, HLA-DR expression on T-cells was unchanged, whereas HLA-DR expression on B-cells did not decrease before the 2nd day after CPB (152 +/- 3 MCF vs. 170 +/- 2 MCF preoperatively, P < 0.001). IN VITRO GM-CSF treatment increased HLA-DR expression on monocytes prepared after CPB to a degree comparable to preoperative values. HLA-DR expression on B-lymphocytes could not be restored by GM-CSF. CONCLUSIONS: Immune system suppression after cardiac surgery is reflected in prolonged diminished HLA-DR expression on monocytes and B-lymphocytes. Suppression is not irreversible but can - at least IN VITRO - be overridden by the immunostimulating compound GM-CSF. PMID- 17285471 TI - Atrial fibrillation after coronary artery bypass grafting in elderly patients: incidence and risk factor analysis. AB - OBJECTIVE: New-onset atrial fibrillation (AF) is the most frequent arrhythmic complication after coronary artery bypass grafting (CABG). Elderly patients who undergo this operation may have a different risk profile from the general population. The aim of this study was to identify risk factors for post-CABG AF in the elderly population. METHODS: Between September 2001 and December 2005, 426 elderly patients (age >/= 65 years) underwent CABG at our center. Ninety-one developed post-CABG AF (AF group), and the other 335 (no-AF group) did not develop this complication. Multivariate analysis (odds ratio, +/- 95 % CI, P value) was used to identify independent clinical predictors of post-CABG AF. RESULTS: The incidence of post-CABG AF in elderly patients during the study period was 21.4 %. Multivariate analysis identified age (OR 1.07, P < 0.009), age >/= 75 years (OR 1.77, P < 0.042), preoperative renal insufficiency (OR 5.09, P < 0.035), EuroSCORE (OR 1.18, P < 0.038), and cross-clamping time (OR 1.02, P < 0.012) as predictors of AF occurrence. The AF group had a significantly longer mean intensive care unit (ICU) stay (3.8 +/- 4.7 vs. 2.5 +/- 1.3 days for AF vs. no-AF; P = 0.0001), and a significantly higher proportion of patients with prolonged (>/= 6 days) ICU stays (8.8 % vs. 3.2 %, respectively; P = 0.033). Hospital mortality was 3.2 % in the no-AF group and 2.2 % in the AF group ( P = 0.74). CONCLUSION: This study of elderly patients reveals some novel predictors of post-CABG AF, most notably preoperative renal insufficiency and EuroSCORE. It is important to identify risk factors for post-CABG AF in all patient groups as this knowledge might lead to better prevention of this problem and its potential consequences. PMID- 17285472 TI - Surgical management of mediastinal goiters: when is a sternotomy required? AB - OBJECTIVE: Mediastinal goiters are frequently diagnosed, particularly in the elderly population. However, factors associated with an increased risk of median sternotomy have not been analyzed systematically. METHODS: Between 1980 and 2004, a total of 185 patients underwent surgery for mediastinal goiters in our institution. There were 126 women and 59 men with a median age of 68 years (range 24 to 94 years). The goiters were left-sided in 77 patients, right-sided in 69 patients, and bilateral in 39 patients. RESULTS: Clinical presentation was mainly dyspnea (37 %), palpation of a cervical mass (35 %), superior vena cava syndrome (5 %), dysphagia (4 %) and dysphonia (4 %). Goiters measured between 5 and 23 cm (median 10 cm) and were prevascular (38 %), retrovascular and paratracheal (33 %), and retrotracheal (27 %). Aberrant intrathoracic goiters were observed in 4 patients (2 %). The large majority of goiters could be removed transcervically, regardless of the location and extension of the goiters. A sternotomy was required in 13 patients (6 %), mainly because of recurrent goiter ( P = 0.1), ectopic goiter ( P < 0.001), or invasive carcinoma ( P < 0.001). Superior vena cava syndrome, emergent airway compression, dysphagia, retrotracheal goiter, or crossover goiters were not found to be associated with an increased risk of sternotomy. One patient (0.5 %) died postoperatively from massive intraoperative carcinomatous pulmonary emboli. Histology demonstrated a thyroid carcinoma in 18 patients (10 %). CONCLUSIONS: Surgery for mediastinal goiters should always be considered, even in elderly patients because of the high risk of tracheal compression and the low morbidity of the surgery. Most mediastinal goiters are benign and can be removed through a cervical approach. Sternotomy should only be performed in cases of previous cervical thyroidectomy, invasive carcinoma, or ectopic goiter. PMID- 17285473 TI - Survival following complete resection of multifocal T4 node-negative NSCLC: a retrospective study. AB - BACKGROUND: Multifocal NSCLC in the same lobe are staged as T4. This study was designed to assess the impact of multifocal NSCLC in the same lobe on survival in completely resected node-negative patients to determine whether the T4 (stage III B) designation is valid. METHOD: We reviewed our database from October 1987 through 2004 to identify completely resected patients with N0 multifocal (T4) NSCLC. Patients with multifocal pure bronchiolo-alveolar carcinoma were excluded. Thirty-two patients had multifocal NSCLC in the same lobe and were node-negative. RESULTS: Five-year survival rate was 42.4 % for the whole group with a median survival of 48 months. When tumors were staged independently of the satellite nodule/s, patients in stage I A had a 5-year survival rate of 55 % while those in stage I B had a rate of 22 %. CONCLUSION: Patients with N0 multifocal intralobar NSCLC should be upstaged but not to stage IIIB. They should undergo complete surgical resection whenever multiple nodules are detected preoperatively. PMID- 17285474 TI - Quantitative lung perfusion following single lung transplantation. AB - BACKGROUND: Following successful lung transplantation, most of the lung perfusion, as well as ventilation, is shifted towards the transplanted lung. We investigated the changes in perfusion during exercise in lung transplant recipients. PATIENTS AND METHODS: Twelve patients were included in the study. Six patients had emphysema and 6 patients had idiopathic pulmonary fibrosis (IPF). Patients underwent two upright lung perfusion scans: the first at rest and the second during a maximal cardiopulmonary exercise test. Lung perfusion was assessed in each lung and regionally. RESULTS: At rest, patients with emphysema had 83.3 +/- 8 % of total perfusion to the transplanted side and 16.7 +/- 8 % to the native lung, while in the IPF patients, it was 68.7 +/- 12 and 32.7 +/- 10 %, respectively ( P = 0.028). At peak exercise, perfusion shifted from the transplanted lung to the native lung ( P = 0.0095) both in emphysema and IPF patients. CONCLUSIONS: Following successful lung transplantation, most of the perfusion is directed towards the transplanted lung. During exercise, there was a small but significant shift towards the native lung. These findings highlighted the important role of the native lung during maximal exercise. PMID- 17285476 TI - Pulmonary homograft endocarditis 19 years after a Ross procedure. AB - We report the case of a patient with acute pulmonary homograft endocarditis secondary to Streptococcus agalactiae from a cat-bite. He had undergone a Ross procedure nineteen years earlier. In view of unremitting infection with large pulmonary trunk and right pulmonary artery vegetations, the patient underwent successful pulmonary vegetectomy and homograft replacement. PMID- 17285475 TI - Mediastinal bronchogenic cyst with respiratory distress from airway and vascular compression. AB - A 45-year-old female, who had undergone emergency drainage of a cyst, complained of severe dyspnea. Chest computed tomography scans showed a large mass, compressing the right pulmonary artery, superior vena cava, and tracheal bifurcation. Subtotal resection of the cyst wall was carried out due to dense adhesion to adjacent structures. Immediately after surgery, her symptoms resolved completely. Mediastinal bronchogenic cysts in the subcarinal space can cause severe respiratory distress from airway and vascular compression. PMID- 17285477 TI - Combined coronary arterial bypass graft and thyroidectomy in a patient with giant goiter: how reliable is it? AB - A 47-year-old male was admitted to our clinic with the complaints of chest pain, limitation of cervical movements, progressive dyspnea, and painless cervical mass. The cervical mass dimensions were approximately 15 x 20 x 25 cm. Laboratory studies revealed a recurrent hyperthyroid state. After the thyroid hormones were maintained in a euthyroid condition, a coronary angiogram was made. It revealed progressive ischemic heart disease. Combined cardiac surgery and total thyroidectomy were performed. The postoperative course was uneventful without any of the problems associated with hyperthyroidism or hypothyroidism. Combined thyroid and cardiac surgery is feasible with little risk for both operations if the perioperative levels of the thyroid hormone are maintained in a euthyroid or hypothyroid state. PMID- 17285478 TI - Combined off-pump coronary artery bypass grafting and aorto-bicarotid bypass. AB - A 63-year-old man with severe coronary artery disease and occlusion of aortic arch branches presented with dizziness, syncope and unstable angina. He underwent a combined surgical procedure of aorto-bicarotid bypass and off-pump myocardial revascularization. The operation was successful and he had no complications during 11 months of follow-up. PMID- 17285479 TI - Left ventricular diverticulum repair in a newborn. AB - We report on a male newborn requiring repair of a huge left apical diverticulum leading to progressive heart failure and extensive ventricular arrhythmia. At the age of 11 days, a modified Dor procedure using an autologous endoventricular pericardial patch was performed. Postoperatively, a significant reduction of ventricular extrasystole was evident. One year postoperatively, the infant demonstrates a normal cognitive and somatic development without clinical signs of cardiac failure. PMID- 17285480 TI - The alkaloid 4-methylaaptamine isolated from the sponge Aaptos aaptos impairs Herpes simplex virus type 1 penetration and immediate-early protein synthesis. AB - We describe in this paper that the alkaloid 4-methylaaptamine, isolated from the marine sponge Aaptos aaptos, inhibited HSV-1 infection. We initially observed that 4-methylaaptamine inhibited HSV-1 replication in Vero cells in a dose dependent manner with an EC50 value of 2.4 microM. Moreover, the concentration required to inhibit HSV-1 replication was not cytotoxic, since the CC50 value of 4-methylaaptamine was equal to 72 microM. Next, we found that 4-methylaaptamine sustained antiherpetic activity even when added to HSV-1-infected Vero cells at 4 h after infection, suggesting that this compound inhibits initial events during HSV-1 replication. We observed that 4-methylaaptamine impaired HSV-1 penetration without affecting viral adsorption. In addition, the tested compound could inhibit, in an MOI-dependent manner, the expression of an HSV-1 immediate-early protein, ICP27, thus preventing the inhibition of macromolecular synthesis induced by this virus. Our results warrant further investigation on the pharmacokinetics of 4-methylaaptamine and propose that this alkaloid could be considered as a potential compound for HSV-1 therapy. PMID- 17285482 TI - Endoscopic detection of colonic tuberculosis in an asymptomatic patient. PMID- 17285481 TI - Cholecysto-pancreatitis due to Ascaris lumbricoides. PMID- 17285483 TI - Appendicitis with a palpable mass. PMID- 17285484 TI - Giant fundic gland polyp mimicking a gastric malignancy. PMID- 17285485 TI - Curative endoscopic resection of a huge pedunculated esophageal liposarcoma. PMID- 17285486 TI - EUS-guided retrieval of a migrated transgastric pancreatic stent. PMID- 17285487 TI - Henoch-Schonlein purpura in an elderly patient with unusual manifestation. PMID- 17285488 TI - Bowel perforation requiring emergency laparotomy and a Hartmann's procedure after a gas explosion induced by argon plasma coagulation. PMID- 17285489 TI - A true Brunner's gland adenoma. PMID- 17285490 TI - Measurement of small-bowel polyp size in patients with Peutz-Jeghers syndrome by using reference granules during video capsule endoscopy. PMID- 17285491 TI - Endoscopic removal of proximally migrated pancreatic stent by a grasping tripod. PMID- 17285492 TI - A new biliary "Y" stent for hilar tumors. PMID- 17285494 TI - Fracture and entrapment of a snare as a complication of colonoscopic polypectomy. PMID- 17285493 TI - Multifocal primary salivary-type adenocarcinoma of the esophagus. PMID- 17285495 TI - Ileal cancer and erosions in the small intestine revealed by capsule endoscopy. PMID- 17285496 TI - Endoscopic features of intestinal follicular lymphoma: the value of double balloon enteroscopy. PMID- 17285498 TI - Feasibility of endoscopic ultrasound-guided embolization of the splenic vein. PMID- 17285497 TI - Polypectomy as a diagnostic tool for ileocecal lymphoma. PMID- 17285499 TI - Permanent closure of a pancreatic duct leak by endoscopic coiling. PMID- 17285500 TI - Cancer of the papilla causing recurrent acute pancreatitis and mimicking a pancreatic stone. PMID- 17285501 TI - Colonic spirochetosis associated with dermatomyositis. PMID- 17285502 TI - Cytomegalovirus infection in an HIV patient with duodenal papillitis. PMID- 17285504 TI - Bleeding jejunal lymphangioma diagnosed by double-balloon enteroscopy. PMID- 17285503 TI - Descending necrotizing mediastinitis after upper gastrointestinal endoscopy. PMID- 17285505 TI - Insidious manifestation of large bowel perforation. PMID- 17285506 TI - Periampullary carcinoid tumor. PMID- 17285507 TI - An ileal metastasis from a parotid gland cancer that mimicked a flat adenoma. PMID- 17285508 TI - Metastasis to the appendix from gastric cancer detected incidentally on colonoscopy. PMID- 17285509 TI - Comparison of commercial and custom-made EUS balloons: technical and clinical evaluation. PMID- 17285510 TI - Pulmonary embolism after sclerotherapy treatment for variceal bleeding. PMID- 17285511 TI - Follicular lymphoma of the duodenum. PMID- 17285512 TI - Extracorporeal shockwave lithotripsy for renal calculi: an unusual cause of common bile duct stricture. PMID- 17285513 TI - Giant gastric and duodenal trichobezoar. PMID- 17285514 TI - The effect of sedation on the quality of upper gastrointestinal endoscopy: an investigator-blinded, randomized study comparing propofol with midazolam. AB - BACKGROUND AND STUDY AIMS: Sedation with propofol is associated with a high acceptance rate in upper gastrointestinal endoscopy. So far, however, there are no valid data on whether the use of propofol can increase the general quality of the endoscopic examination. PATIENTS AND METHODS: A total of 60 patients referred for upper gastrointestinal endoscopy were randomized to receive sedation with either midazolam (n = 30) or propofol (n = 30). The maximum dosages permitted were 5 mg of midazolam and 500 mg of propofol. The examinations were recorded on videotapes, and the quality of upper endoscopy was assessed by videotape analysis by three experienced endoscopists who were all blinded to patient data and the medications used for sedation. A score sheet was used with 18 assessment items that each represented a step of upper gastrointestinal endoscopy and a global score for the entire examination. A scale ranging from 1 (excellent) to 6 (very poor) was used. Data were analyzed on an intention-to-investigate basis: inability to perform the procedure because of a patient's intolerance of the procedure, for example, was scored as 6 (i. e. very poor). RESULTS: Patients in the two groups were well matched with respect to demographic and clinical data. Four patients in the midazolam group could not be adequately examined. The median dosage used for sedation was 5 mg midazolam (range 2-5 mg) and 160 mg propofol (range 70-320 mg). When assessments by all three blinded examiners were added together, propofol sedation was found to result in significantly better scores for all parameters except for the assessments of "Z-line/cardia", "duodenal bulb", and "duodenal folds" (all P < 0.05, Mann-Whitney U test). CONCLUSION: Sedation with propofol might increase the quality of upper endoscopy. This finding may have a significant impact on the selection of the type of sedation, not only in terms of increasing patients' acceptance of the procedure, but also for improving the diagnostic accuracy of upper gastrointestinal endoscopy. PMID- 17285515 TI - [Alzheimer's disease, category-specific impairment and relevant variables in object naming]. AB - INTRODUCTION: The study of the dissociations or category-specific effects between the domains of living beings and non-living beings in Alzheimer's disease (AD) is a controversial issue in the cognitive neurosciences. The lack of agreement among the different studies may be due to deficient control of certain cognitive and psycholinguistic variables that affect processing of the items. AIM: To determine whether the presence of category-specific effects in AD can be caused by inadequate control of variables, such as the typicality or familiarity of the items. Furthermore, since the groups may contain different types of patients with opposing impairments (which would mask this kind of effect in the group analysis), both group and individual analyses were conducted. SUBJECTS AND METHODS: A retrospective study was carried out to evaluate 66 participants (32 patients with AD) using a colour photo naming task with items controlled for seven disruptive variables. RESULTS: No evidence of living/non-living dissociation was found in the analyses by groups, although the individual-based analysis did show some cases of category-specific effects. CONCLUSIONS: Our data show that category-specific effects are not as widespread as they were believed to be and that the lack of control over the so-called disturbing variables may play an important role in studies on category-specific impairment. Our study also highlights the importance of conducting individual analyses in order to avoid overlooking certain effects that are masked in the group studies. PMID- 17285516 TI - [Immediate and long-term outcomes of carotid endarterectomies in eighty-year olds]. AB - AIMS: To compare the immediate results obtained after performing a carotid endarterectomy (cEDA) in patients in their eighties with those of younger patients, and to determine survival and stroke-free times following carotid surgery in the two groups. PATIENTS AND METHODS: Retrospective data was collected regarding a series of 319 cases of cEDA (302 patients) performed between January 1998 and December 2004. Group 1: patients aged 80 or above. Group 2: the rest of the series. Sample follow-up: clinical and by means of carotid duplex. RESULTS: Mean age of the sample: 70.7 years (41-86). Group 1 was made up of 30 patients (9.4% of the series). Mortality rate: group 1, 3.3%; group 2, 1%; p=0.32. Major stroke-death incidence: group 1, 6.7%; group 2, 1.4%; p= 0.1. Median follow-up time: 36 months (1-87). Total mortality of the series throughout follow-up: 36 patients (12.6%). Mortality rate: group 1, 25%; group 2, 11.3%; p=0.04; relative risk: 2.6 (1.02-6.7). Stroke: group 1, 14.3%; group 2, 2.3%; p=0.01; relative risk: 7 (1.8-26.4). At five years, 96.7% were free of strokes (group 1: 84%; group 2, 97.7%; p=0.0001). At five years, 82.4% survived free of strokes (group 1: 61%; group 2, 84.4%; p=0.004). CONCLUSIONS: The risk of perioperative complications is higher in patients in their eighties than in younger patients, although the increase is not statistically significant. Even though the risk of a stroke during follow-up was higher in the eighty-year-olds, 84% of the subjects in this group remained stroke-free at five years. The high stroke-free survival rate in the medium to long term means that cEDA can be especially beneficial for patients in their eighties. PMID- 17285517 TI - [Video-EEG evaluation complemented by spectral and EEG source analysis in patients with medication-resistant medial temporal lobe epilepsy]. AB - AIM: To evaluate the value of prolonged video-electroencephalographic (video-EEG) monitoring complemented with spectral and EEG source analysis in identifying the epileptogenic area in patients with medial temporal lobe epilepsy who are candidates for non-lesional resective surgery. PATIENTS AND METHODS: The electrographic patterns during the onset of seizures were evaluated in over 667 seizures from 41 patients with a clinical diagnosis of medication-resistant partial epilepsy. Analyses were performed using Harmonie software and variable resolution electrical tomography (VARETA). RESULTS: Video-EEG was used to determine that 53.6% of the patients evaluated suffered complex partial seizures of a temporal origin; these were characterised by having an average frequency of 5.56 +/- 1.56 Hz, while the non-temporal seizures displayed a frequency within the range 9.17 +/- 3.32 Hz. The topographic location of the dominant ictal frequency during the period of maximum spectral energy in patients with temporal lobe epilepsy enabled us to draw a distinction between a group of patients with mesial seizures and those with non-mesial seizures that exceeded the number that was determined by visual inspection of the EEG, that is, 78.9 versus 47.3%, respectively. There was a 100% coincidence between the area where the seizures began as defined by surface EEG complemented with spectral analysis, the generator of this activity as defined by VARETA and the epileptogenic region. CONCLUSIONS: The localising information provided by video-EEG complemented with spectral and EEG source analysis allows for non-invasive location of the epileptogenic region in patients with medial temporal lobe epilepsy even when structural imaging studies show an absence or bilaterality of abnormalities. PMID- 17285519 TI - [Clinical features of familial Creutzfeldt-Jakob disease and the E200K mutation in Spain]. AB - INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is an infrequent pathology affecting the central nervous system (about 1/1,000000) that has a subacute progression and, for the time being, a fatal prognosis. The familial forms account for between 5-10% of cases and one of the most frequent is that produced by the E200K mutation of prion protein gene (PRNP), which has not been reported in Spanish families although Spain is considered to be part of the expansion circuit of the mutation. CASE REPORTS: We report on a Spanish family with three cases of CJD. The disease affected three females (our patient and two paternal aunts), who started with dementia, myoclonias, gait disorders and cortical blindness at the ages of 61, 53 and 55 years. Progress in all three cases was torpid and the symptoms advanced in a short time. Results of the complementary tests that were carried out were normal, except for the electroencephalogram, which was compatible with CJD in all three cases, and the imaging tests, which revealed cortical-subcortical atrophy. A confirmatory diagnosis was reached from a biopsy, the clinical picture and the family history in the cases of the paternal aunts and from a genetic study of our patient, which confirmed the E200K mutation. CONCLUSIONS: This family confirms the presence of familial forms of CJD in Spain, more specifically the E200K mutation, and highlights the role of Spain in the possible transmission of this mutation. PMID- 17285518 TI - [Motor assessment in school-aged children with indicators of the attention deficit/hyperactivity disorder]. AB - INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) is one of the most frequent disorders in childhood. In the literature there are claims that ADHD is associated with important comorbidities, which include disorders affecting motor coordination. AIM. To evaluate motor development of schoolchildren with ADHD indicators. PATIENTS AND METHODS: The sample used in our study consisted of 31 schoolchildren (aged between 7.3 and 10.8 years) studying in the first and second years of primary education in state-run schools in Florianopolis, SC, Brazil, who had ADHD indicators in accordance with DSM-IV (Diagnostic and statistical manual of mental disorders) and attention deficit with hyperactivity disorder evaluation scale (EDAH) criteria, which had been answered by teachers and parents. Motor evaluation was evaluated using the Motor Development Scale. The Epi Info 3.2.2 software application was used for descriptive statistics. RESULTS: Findings showed that 48.4% of the schoolchildren had a motor development that was considered to be 'low average' according to the Motor Development Scale; 35.5% were 'inferior'; 9.7% were 'very inferior'; and 6.4% were found to be 'medium average'. The mean motor development of the group as a whole was classified as being 'low average'; the greatest difficulties were temporal organisation ('very inferior'), spatial organisation ('inferior') and balance ('inferior'). Fine motor control, general motor control and body schema were classified as 'low average'. With respect to laterality, 48.4% were right-handed, 48.4% had crossed laterality and 3.2% had undefined laterality. CONCLUSIONS: These results are in line with studies that suggest the existence of alterations in the motor coordination of children with symptoms of ADHD. PMID- 17285520 TI - [Neuroschistosomiasis: a challenging diagnosis]. AB - INTRODUCTION: Neuroschistosomiasis is an uncommon and under diagnosed disease in our country because of the no clinical suspicion. The most common neurological manifestations are epileptic seizures as central nervous system involvement or different types of myelopathies: transverse myelitis, myeloradiculopathy, cauda equina syndrome or Brown-Sequard syndrome. CASE REPORT: A 27 years-old male from an endemic area, with atypical neurological affectation as he presented myelopathy and multifocal neuritis. Diagnosis was based on the epidemiological exposure datums, the myelopathy, the positive serological studies for Schistosoma haematobium, no detection of other parasitic infections and the clinical and radiological improvement after treatment. Cervical and thoracic magnetic resonance showed areas of hyper signal in T2 as it was described in other cases. It was detected S. haematobium in the bladder, the rest of serological and microbiological studies were negative. Besides, eosinophils on the biopsy of sural nerve orientative to parasitic etiology. CONCLUSION: In patient with myelopathy or another unexplained neurological manifestation we have to suspect neuroschistosomiasis. In a world where migrations and travels are so frequent we have to think in this type of diseases. PMID- 17285521 TI - [Inverted or tilted perception disorder]. AB - AIM: In the context of the increasing number of reported cases of patients presenting tilt or reversal of vision anomaly (here reviewed), we call the attention to the work of Justo Gonzalo (1910-1986), scarcely known in the contemporary literature. His work deals with that anomaly, and with tactile and auditory inversion, in relation to what he called central and paracentral syndromes, interpreted from the functional model he developed. DEVELOPMENT: Gonzalo makes reference to 25 patients with chronic tilted vision, some of them with almost inverted perception in visual, tactile and auditory systems, under minimum stimulus. The central syndrome is caused by unilateral lesion in the parieto-occipital cortex, equidistant from the visual, tactile and auditory projection areas, and is characterized by bilateral multisensory involvement, and by dynamic effects following physiological laws of nervous excitability. Thus, as the illumination of an object was diminishing, it was perceived progressively tilted, reduced, and losing form and colors, following a physiological order; however the image was corrected by increasing the illumination, or by facilitation through other sensory stimulus. The central syndrome is compared with the reviewed cases. CONCLUSIONS: This syndrome involves a deficit of nervous excitability which would induce an integration deficit, tilted vision emerging as a more common affection than believed. The central syndrome reveals aspects of the cerebral dynamics, suggesting a functional continuity and unity of the cortex. This is reflected in the model that was proposed, based on functional gradations through the cortex and scaling laws of dynamic systems. PMID- 17285522 TI - [Neuropsychological evaluation in multiple sclerosis]. AB - INTRODUCTION: In recent years, advances have occurred in the description of cognitive alterations in multiple sclerosis (MS) patients and the development of tools for their assessment. However, in the clinical practice, the neuropsychological assessment of these patients is often non-specific and lacks appropriate standardization. Therefore the development of neuropsychological tests and batteries sensitive and specific for detecting the cognitive alterations in MS patients has become an important subject of study. AIM. To provide a short review about the recent developments in the neuropsychological assessment of MS patients. DEVELOPMENT: We introduce and discuss various sensitive and valid tests that assess cognitive functions often altered in MS patients. In addition, because of their possible impact on cognitive performance, we also present guidelines for evaluating other frequently associated problems (such as mood disorders and fatigue) in MS patients. CONCLUSIONS: The use of sensitive and specific tests makes possible to assess the neuropsychological alterations associated with MS, however, the adaptation of such tests to languages other than English (i.e. Spanish) has just begun. Besides assessing cognitive functioning, the neuropsychological assessment of MS patients should also involve the evaluation of other variables (such as depression or fatigue) that may influence cognitive performance. Improvements in assessing these domains should help to provide better and more specific protocols for the neuropsychological evaluation of MS patients. PMID- 17285523 TI - [Contributions of neuroscience to the diagnosis and educational treatment of developmental dyslexia]. AB - AIM: To examine the advances made in the fields of cognitive psychology, neuroscience and education and how they have contributed to each other. DEVELOPMENT: The paper offers a review of the current models of dyslexia and analyses the relation between these models and neuroimaging studies and educational intervention. The first model presented here is the 'phonological deficit' model, which is the most widely proven and accepted today. People with dyslexia have difficulty in completing tasks that involve segmenting language at a phonological level. Neuroimaging studies also reveal the existence of atypical brain activation in dyslexics while performing tasks that require phonological processing. Intervention programmes of a phonological nature have proved to be effective on both a behavioural and a neurophysiological level. Given the complexity of the reading process, further research is currently looking into other models. Although the 'temporal processing' deficit model is more controversial and not as widely accepted as the previous model, some reports provide both behavioural and neurophysiological evidence for the existence of differences in the visual and auditory processing of dyslexic and control subjects. Different educational approaches to put this temporal processing deficit to rights have been tested in dyslexic children with successful outcomes. Finally, the present status between neuroscience and education in the area of reading disorders is examined and future implications concerning the different approaches and methods used in current research are analysed. CONCLUSIONS: Although we are still a long way from understanding the causes of reading deficiencies, collaboration between neuroscience, psychology and education does help further our understanding of the psychology of reading, its diagnosis and its intervention. PMID- 17285524 TI - [Neurological illness in the process of canonising Saint Dominic de Guzman]. AB - INTRODUCTION: Dominic de Guzman, the founder of the Order of Preachers (or Dominicans), was one of the most influential and outstanding figures in medieval Hispania. His canonisation process was endorsed by a good number of miraculous healings that took place thanks to his intervention. The descriptions of the people he cured contain several clinical pictures that are compatible with neurological diseases. DEVELOPMENT: We review the records of the canonisation process that have survived in various biographies of the saint written in the Middle Ages. We also study other descriptions of pathologies that appear in the hagiographical texts by the first Dominican monks. Six of the miracles included in the records of the canonisation process describe clinical signs and symptoms that can be interpreted as being of a neurological nature. The most striking are those concerning a young male with acute lumbar-radicular pain with motor involvement, a female with a clinical picture compatible with a cervical central cord disorder and another young male probably suffering from acute myositis. The biographies of the first preacher monks describe deficiency symptoms in the dominant hemisphere and a case of Parkinson's syndrome, among others. CONCLUSIONS: Medieval literature, in the early hagiography of the Dominican order, provides us with exquisite, interesting descriptions of neurological clinical cases which are outlined in this paper. PMID- 17285525 TI - [Fat embolism syndrome]. PMID- 17285526 TI - [Defensive cranial computerised tomography scan]. PMID- 17285527 TI - [Auriculotemporal nerve syndrome in children secondary to a forceps delivery]. PMID- 17285528 TI - [Charles Bonnet syndrome]. PMID- 17285529 TI - [The real filtering role played by the primary care physician]. PMID- 17285531 TI - [Access to the neurologist]. PMID- 17285533 TI - [Prenatal diagnosis of X-linked adrenoleukodystrophy]. AB - OBJECTIVE: To make prenatal dignosis of X-linked adrenoleukodystrophy (ALD) for the prevention of the disease. METHODS: Eighteen amniocenteses were performed on 17 suspected carriers of X-ALD during 18-30 gestation weeks. The very long chain fatty acids (VLCFAs) levels of cultured amniocytes were tested by gas chromatography-mass spectrometry (GC/MS). The plasma VLCFAs levels were measured in 8 of the 18 prenatal diagnosed children when they were born or after abortion. ABCD1 gene mutation analysis was carried out in 8 cases by PCR and sequencing. ALDP of amniocytes was tested by Western blotting in 2 cases from a family, one female, another male, and the VLCFAs of cultured amniocytes were increased in both of them. RESULTS: Among the 18 fetuses, 10 were males and 8 were females. The VLCFAs levels of the cultured amniocytes were increased in 3 males and 4 females. The postnatal plasma VLCFAs were normal in 5 cases with normal VLCFAs levels of amniocytes, and increased in 3 cases with high VLCFAs levels of amniocytes. ABCD1 gene mutations were found in 4 cases with high VLCFAs levels of amniocytes, no mutation was found in other 4 cases with normal VLCFAs levels of amniocytes. ALDP of amniocytes could be detected in the female with high VLCFAs levels of amniocytes, and it could not be detected in the male with high VLCFAs levels of amniocytes. Three male fetuses with high VLCFAs levels of amniocytes were aborted. The others who were born were normal clinically so far. CONCLUSION: The prenatal diagnosis is very important for the prevention of ALD. Amniocyte VLCFAs level analysis combined with ABCD1 gene mutation analysis and ALDP test could make a proper prenatal diagnosis. PMID- 17285534 TI - [Influence of maternal age on meiotic spindle and chromosome configuration of oocytes]. AB - OBJECTIVE: To study the effect of maternal age on meiotic spindle and chromosome configuration of oocytes. METHODS: Spindle and chromosome configuration was examined in day 1 unfertilized human oocytes after in vitro fertilization (IVF) and intracytoplasmic sperm injection(ICSI) by immunocytochemistry and visualized by laser confocal microscopy. RESULTS: Statistically significant differences were observed on normal spindle and chromosome configurations of oocytes between 25-29 maternal age group (33% and 31%, respectively), and 30-34 age group (P< 0.05) as well as 35-40 age group(0%, P<0.01). The incidence of abnormal spindle and chromosome configurations of oocytes from 30-34 and 35-40 maternal age groups was much higher than that of oocytes from 25-29 age group (P<0.01, P<0.05). CONCLUSION: Incidence of abnormal spindle and chromosome configuration of oocytes is related to maternal age. It could be an important reason of age related oocyte aneuploidy. PMID- 17285535 TI - [Loss of imprinting of IGF2 in cord blood of newborns of Chinese Han population]. AB - OBJECTIVE: To study the imprinting status of IGF2 and phenotypes of loss of imprinting (LOI) in cord blood of neonates of Chinese Han population and to investigate relative factors to LOI. METHODS: Cord blood of 1010 Chinese Han newborns were collected and the imprinting status of IGF2 was detected by reverse transcription-PCR(RT-PCR) and restriction fragment length polymorphism.The relationships between LOI and fetal growth indices, features of parents and grandparents, clinical characteristics were analyzed. RESULTS: Of all cases, 42.8% (432/1010) were heterozygous for a polymorphism of Apa I site in exon 9 of IGF2, while 21.6%(66/306) displayed IGF2 LOI. Maternal factors including average age, gestational age, BMI pre-pregnancy, weight gain during pregnancy and the level of HB, HCT, and other indices of biochemistry in their second and third trimester were not correlated with LOI expression. However in newborns with fathers older than 35 yrs, 31.7%(19/60) displayed LOI, which was significantly more common than that in newborns with younger fathers (P< 0.05, chi square is 4.69). There were no difference in birth weight (BW) between normal imprinting and LOI groups. But if the newborn's weights were in 2500-2999 g, LOI was 6.25%(2/32), which was significantly lower than that in 3000 g group (P< 0.05, chi square is 4.89). In groups with BW being less than 2500 g and more than/equal to 4000 g, the LOI newborn's blood glucose was decreased significantly after 2 hrs (P< 0.01, t is 7.47 and 10.9). CONCLUSION: In newborns of Chinese Han population, 21.6% showed IGF2 LOI in cord blood. IGF2 LOI may have some influences on fetal growth. Paternal age is associated with LOI. PMID- 17285536 TI - [SPG3A-hereditary spastin paraplegia with genetic anticipation and incomplete penetrance]. AB - OBJECTIVE: To analyze the SPG3A coding sequence and clinical features in a family with dominantly inherited hereditary spastin paraplegia (HSP) characterized by incomplete genetic penetrance and genetic anticipation. METHODS: Analysis of the SPG3A coding sequence, being sequence variations in SPG4/spastin (S44L and P45Q) and SPG6/nipa1([GCG]5-11) genes were performed for the proband, his affected son, his unaffected parents and unaffected brother. One hundred normal individuals were selected as controls. RESULTS: SPG3A mutation V253I in the proband, his affected son, and unexpectedly, in his asymptomatic, 72 year old father was identified. No mutation at the same site was found in the other members of this family as well as the control. CONCLUSION: Incomplete genetic penetrance due to SPG3A mutation V253I was observed in this family. This is the second report. Marked phenotype variation (genetic non-penetrance, adult versus childhood onset symptoms) between subjects with the same SPG3A mutation indicates the influence of modifying genetic or environmental factors. Progressively earlier symptom onset and increasing symptom severity in this family is consistent with genetic anticipation which has not been previously reported in SPG3A-HSP. PMID- 17285537 TI - [New compound heterozygous mutation causes partial combined 17 alpha hydroxylase/17,20-lyase deficiency]. AB - OBJECTIVE: To investigate the CYP17A1 gene mutations in a Chinese 46,XX patient with partial combined 17 alpha-hydroxylase/17,20-lyase deficiency. METHODS: Clinical data were retrospectively analyzed. The genomic DNA of the patient and her parents was isolated from whole blood. Seven pairs of primers were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. In order to confirm the DNA sequences of different alleles, some fragments were inserted into pMD 18-T vector and then subclone sequenced. Sequencing results were compared to the established human CYP17A1 sequence. RESULTS: The patient was new compound heterozygous of 5994-5995 delAT/7541 C>T. The mutation 5994-5995 del AT, causing amino acid I259H, 274X, was proposed to result early truncated protein which was lack of the activity center site of P450C17, whereas missense mutation 7541 C>T causing A398V did not lie in the active site of the enzyme according to the computer model of human P450C17. The 46, XX case had irregular menstruation and slightly hypertension and hypokalemia. The ACTH stimulating test as well as the result of the sex hormones suggested that there was partial 17 alpha hydroxylase/17, 20-lyase enzyme activities in the adrenal and sexual gland. We speculate that A398V might conserve partial of the enzyme's activities. The genotype was coincident with phenotype. CONCLUSION: More study should be done to have better understanding of the function of the mutated P450C17 enzymes. PMID- 17285538 TI - [Association of genetic polymorphisms in endothelial nitric oxide synthase 3 gene with recurrent early spontaneous abortion]. AB - OBJECTIVE: To explore the association of nitric oxide synthase 3 (NOS3) gene variable number of tandem repeat(VNTR) polymorphism in intron 4 and an 894(G/T) mutation at exon 7 with recurrent early spontaneous abortion (RESA). METHODS: One hundred and forty RESA women (patient group) and 140 healthy women with at least 1 pregnancy and without a history of pregnancy complications (control group) were included. The genotypes of NOS3 gene VNTR polymorphism were determined by polymerase chain reaction and agarose gel electrophoresis. The 894(G/T) mutation of genotypes of NOS3 gene at exon 7 was assessed by polymerase chain reaction restrictive fragment length polymorphism. RESULTS: The frequencies of aa and ba genotypes and a allele of NOS3 gene were higher in patient group than in control group (chi square: 4.51, P< 0.05; chi square: 4.29, P<0.05). The aa and ba genotypes were significantly associated with RESA (OR:1.8, 95% CI: 1.04-3.24). There was no significant difference in TT and GT genotypes and T allele of NOS3 gene between RESA patient group and control group (chi square: 1.16, P> 0.05; chi square:1.12, P> 0.05). 894(G/T) polymorphism may be not associated with RESA. CONCLUSION: The genetic polymorphism of NOS3 gene 27 bp VNTR was associated with RESA. The genetic polymorphism of NOS3 gene 894(G/T) may be not associated with RESA. These results support that a allele of the NOS3 gene may be susceptibility allele. PMID- 17285539 TI - [Relationship between adiponectin receptor 1 gene -3881T/C variant and glucose metabolism in the Chinese]. AB - OBJECTIVE: To investigate the relationship between adiponectin receptor 1 gene (ADIPOR1) single nucleotide polymorphism (SNP) and glucose metabolism and insulin resistance in the Chinese. METHODS: The genotypes of -3881T/C of ADIPOR1 were determined through polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in 664 Chinese in Shanghai. Among them, 370 were subjects with normal glucose tolerance and 294 were newly diagnosed diabetic patients without taking any drug. Phenotype measured were: height, weight to calculate body mass index; systolic blood pressure and diastolic blood pressure; plasma glucose level, serum insulin and C-peptide levels of blood obtained both at 0 and 120 minute during a standard 75-gram glucose oral glucose tolerance test. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). RESULTS: (1) The frequencies of two alleles did not differ between the type 2 diabetic patients and ones with normal glucose tolerance (P is 0.6749). (2) The frequency of C allele is significantly lower in type 2 diabetic patients with insulin resistance compare with those without insulin resistance (P is 0.0121). (3) In type 2 diabetic patients, the C allele carriers had a significantly lower diastolic blood pressure (P is 0.0466) and HOMA-IR (P is 0.0498). (4) In subjects with normal glucose tolerance, the C allele carriers had a significantly lower fasting plasma glucose (P is 0.0140). CONCLUSION: These findings suggest that variant of ADIPOR1 plays a role in glucose metabolism and insulin resistance in the Chinese. PMID- 17285541 TI - [The family investigation of a weak D type 15 donor]. AB - OBJECTIVE: To study the genetic feature of weak D type 15 allele (RHD845A) in a Chinese family. METHODS: Rh D, C, c, E and e phenotypes of 4 members in a weak D type 15 family were tested by serological and polymerase chain reaction (PCR), D antigen was proven by indirect antiglobulin test. A pair of primers specific for RHD845A were designed, and a sequence specific primer-PCR (PCR-SSP) method was established to detect RHD845A allele in all family members. Subsequently the dual tube PCR method was used to determine the RHD zygosity of 4 members. RESULTS: The RHD845A allele existed in all 4 family members and the RHD zygosity test showed that all members were RHD +/RHD + homozygous. The parents and nephew possessed one normal RHD gene as RHD845A allele carriers, which caused RhD positive. The proband and his old-sister took two RHD845A alleles, which caused weak D phenotype. CONCLUSION: The proband is the weak D type 15 allele homozygous. The weak D type 15 gene is an ancestral allele, but not a mutation. PMID- 17285540 TI - [Mutational analysis of EGFR and K-RAS in Chinese patients with non-small cell lung cancer]. AB - OBJECTIVE: To investigate gene mutations of the epidermal growth factor receptor (EGFR) and K-RAS in Chinese non-small cell lung cancers (NSCLCs). METHODS: Mutations of exons 18, 19 and 21 of the EGFR and codons 12, 13 of the K-RAS in 101 NSCLCs were detected by PCR-amplifying and gene sequencing, and the relationship between mutations and clinical characters of NSCLCs and response to gefitinib were analyzed. RESULTS: Overall, 26 EGFR mutations (25.7%), 3 K-RAS mutations (2.9%) were detected, and EGFR mutation frequencies in adenocarcinomas, nonsmoker and female were found to be high (44.2%, 65.7% and 48.3% respectively). Nine out of 10 gefitinib treated patients with disease control was found with EGFR mutation. CONCLUSION: The data suggest that mutation frequency of EGFR in NSCLCs from Chinese patients is higher than that of western ethnicities, such mutations are well correlated with tumor response to gefitinib, and gefitinib is more fit for Chinese NSCLC patients. PMID- 17285542 TI - [Association analysis of the parkin gene in patients with sporadic Parkinson's disease from a Han population of Sichuan province]. AB - OBJECTIVE: To determine whether there are any associations between the -258T/G polymorphism of the promoter and the IVS3 -20T/C polymorphism in parkin gene and Parkinson's disease (PD) from a Han population in Sichuan province. METHODS: Polymerase chain reaction (PCR), restriction fragment length polymorphism, denaturing high performance liquid chromatography(dHPLC) and sequence analysis were used to determine the genotype of each subject. The -258T/G polymorphism and IVS3 -20T/C polymorphism were analysed in 198 patients with sporadic PD and 187 healthy controls, matched for age and gender. RESULTS: There were significant differences in allele frequency of the -258T/G polymorphism between PD patients and controls, with the G allele more common in cases than controls (52.5% vs 43.3%; chi square is 6.17, P< 0.025, OR is 1.45, 95% CI 1.04-1.86). There were also significant differences in G allele frequency between PD patients with onset age over 50 years old and controls(chi square is 9.048, P< 0.01, OR is 1.57, 95% CI:1.08-2.06). The frequency of TG+GG genotype was significantly higher in PD patients than in controls (78.79% vs 69.51%; chi square is 3.854, P< 0.05, OR is 1.63, 95% CI:0.88-2.38). In addition, there were significant differences in age of onset between PD patients with different genotypes (P< 0.05). The average age of onset in group of GG genotype was later about 5 years compared with the group of TT or TG genotype. The frequency of CC genotype in IVS3 -20T/C polymorphism was much higher than that of TC genotype. No TT genotype was found. CONCLUSION: This study suggests that the parkin promoter -258T/G polymorphism might be a risk factor for late onset PD in Sichuan. CC genotype for IVS3 -20T/C polymorphism is common in Sichuan Han population. No TT genotype for IVS3 -20T/C polymorphism is found in Sichuan Han population. PMID- 17285543 TI - [Expression of fusion gene PAX3/PAX7-FKHR and chromosomal aberration in rhabdomyosarcoma]. AB - OBJECTIVE: To detect the PAX3/PAX7-FKHR fusion transcripts to identify genetic alteration in embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) tissues. METHODS: One-step reverse transcription- polymerase chain reaction (RT-PCR) were used to detect the expression of the PAX3/PAX7-FKHR fusion transcrips in 16 cases of rhabdomyosarcoma (7 cases of ARMS, 9 cases of ERMS) and 16 specimens were compared to the surrounding normal tissue. Comparative genomic hybridization (CGH) was employed to detect the genomic imbalance (DNA loss or amplification) in 16 RMS cases. RESULTS: PAX3-FKHR fusion transcripts were positive in 3/7 and PAX 7-FKHR fusion transcripts were positive in 2/7 of ARMS patients, respectively, and were all negative in ERMS and Control tumors. There were different chromosome variations for each RMS, chromosome amplification was frequently seen in 1p36 (69%), 5q32 (56%), 8q21 (63%), 13q14 (69%), 19q (63%), 20q (56%). Chromosome loss was frequently seen in 3p21-pter (56%), 9p23-pter (50%), 10q (69%), 16/16q24 (56%). CONCLUSION: One-step RT-PCR assay for detection specific fusion gene provides a useful tool for confirmation of the diagnosis of RMS in diagnostically difficult cases and in retrospective studies. Chimeric gene transcript resulting from specific chromosomal translocations is a reliable index for the molecular diagnosis of RMS. PMID- 17285544 TI - [Study on the association of single nucleotide polymorphisms and haplotypes of GPR154 gene with allergic asthma in Han nationality in Hubei Chinese population]. AB - OBJECTIVE: To investigate whether two polymorphism sites of the G protein-coupled receptor 154 gene (GPR154) are associated with asthma in Han nationality of Hubei province in China. METHODS: The polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 145 cases of allergic asthma and 120 healthy controls. RESULTS: (1)The genotype frequencies of SNP563704 were 0.324 for CC, 0.524 for CT, 0.152 for TT in allergic asthma patients in a Chinese population. The genotype frequencies of SNP522363 were 0.289 for CC, 0.521 for CG, 0.190 for GG in allergic asthma patients in a Chinese population. (2)No significant differences in the distributions of SNP563704 and SNP522363 polymorphisms were found between allergic asthma and healthy control subjects (chi square is 1.880, P> 0.05; chi square is 0.700, P> 0.05, respectively). (3)No significant difference in serum total IgE was found between patients with allergic asthma with different genotypes of SNP563704 and SNP522363 (F is 0.714, P> 0.05; F is 0.083, P> 0.05, respectively). (4) The distribution of frequencies of 4 haplotypes showed significant difference(chi square is 16.50,P< 0.01). The haplotype frequencies of CT and GT were remarkably higher in asthma subjects than those in controls. CONCLUSION: The polymorphisms of SNP563704 and SNP522363 are not associated with allergic asthma in Han nationality in Hubei Chinese population. However, the haplotypes are associated with allergic asthma. PMID- 17285545 TI - [Proteomic analysis of the ankle joint bone, ankle joint tissue and spinal cord of clubfoot-like deformity in rat fetuses]. AB - OBJECTIVE: To explore the etiology of idiopathic talipes equinovarus (ITEV) in all-trans retinoic acid (ATRA) induced clubfoot-like deformity in rat fetuses with two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). METHODS: Clubfoot-like deformity model in rat fetuses was induced with ATRA (135 mg/kg) in gestation day (GD10) pregnant Wistar rats. 2-DE was applied to separate the total proteins of ankle joint tissue, ankle joint bone and spinal cord of the animal models. The Coomassie Brilliant Blue staining gels were analyzed by 2-DE software PDQuest 7.1.0. Selected differential protein spots were identified with peptide mass fingerprinting based on matrix-assisted laser adsorption/ionization time-of-flight mass spectrometry and database searching. xiap, tnnt1 and col2 alpha 1, three genes of the differential proteins, were identified furthermore. Apoptosis study was made in terminal deoxynucleotidyl transferase nick end labeling. RESULTS: There were many differential expressed proteins in the clubfoot-like deformity model. Out of the differentially expressed proteins,16 protein spots were identified to be differentially expressed in the clubfoot-like deformity model with MS. Three of the 16 protein spots, xiap, tnnt1 and col2 alpha 1 were confirmed to be significantly down-regulated by the RT-PCR, and Xiap was further confirmed to be significantly down-regulated with immunohistochemistry. Another randomly selected gene, ngfr, did not express differently in ATRA-induced clubfoot-like deformity in rat fetuses. The rates of the apoptosis in the spinal, bone of the clubfoot-like deformity fetuses was 5.4 and 10 times of those of the normal fetuses respectively. CONCLUSION: The results suggest that there are certain differently expressed proteins in ankle joint tissue, ankle joint bone and spinal cord of the ATRA-induced clubfoot-like deformity in rat fetuses, and Xiap, sTnT, and Col2 alpha 1 show a significant correlation with ITEV. Ngfr is not correlation with ITEV. Apoptosis plays a key role in the development of ITEV and related to the decreased expression of the Xiap. PMID- 17285546 TI - [A study on the expression of CASP9 gene and its polymorphism distribution in non small cell lung cancer]. AB - OBJECTIVE: To explore the expression of caspase 9(CASP9) gene in non-small cell lung cancer (NSCLC) and single nucleotide polymorphism (SNP) distribution of CASP9 in NSCLC patients and normal people. METHODS: Reverse transcription-PCR (RT PCR) was used to analyze the expression of CASP9 in 81 NSCLC and normal lung tissues. Two SNPs in CASP9 gene were chosen to be investigated. Genotypes of rs1052576 and rs1052571 in 81 NSCLC patients and 100 normal people were analyzed by PCR-restriction fragment length polymorphism (PCR-RFLP). Legally constituted authority statistical analysis was applied to analyze SNP genotype frequency and allele frequency in patients and control group. RESULTS: In comparision with normal lung tissues, CASP9 gene expression was obviously down-regulated in 44.4% (36/81) NSCLC tissues. rs1052571 located in exon 1 of CASP9 gene had no significant difference between two groups, rs1052576 located in exon 5 of CASP9 gene had significant difference between two groups, the G allele frequency in NSCLC patients was higher than those in healthy controls (P< 0.05); the AG genotype frequency in patients with lymph node metastasis was higher than those without lymph node metastasis (P< 0.05). CONCLUSION: This study confirms the association between CASP9 gene and NSCLC oncogenesis, rs1052576 which locates in exon 5 of CASP9 gene is associated with NSCLC. AG genotype has association with lymph node metastasis. PMID- 17285547 TI - [Multiplexed mutagenically separated PCR assay for rapid detection of SNP loci in mitochondrial DNA coding region]. AB - OBJECTIVE: To develop a multiplexed mutagenically separated PCR (MS-PCR) for single nucleotide polymorphism (SNP) loci typing in mitochondrial DNA coding regions and to study the applications in investigating the allele frequencies and haplotypes of four SNP loci in mitochondrial DNA coding regions in Chinese Chengdu Han population. METHODS: Four SNP loci C12705T, A8701G, G8584A and C10400T, two allele specific forward primer with 4 bases different in size and a common reverse primer were designed for SNP typing. The primers simultaneously were amplified in a single tube. The genotyping of SNPs was determined by the two allele specific fragments different in size after polyacrylamide gel and silver staining. RESULTS: The different SNP loci comprised a single band with different size respectively. Typing results were completely consistent with those by direct sequencing. The allelic frequencies of C12705T, A8701G, G8584A and C10400T were 0.3813/0.6187, 0.4813/0.5187, 0.8250/0.1750 and 0.4938/0.5062 respectively. A total of 6 different haplotypes was identified and the genetic diversity reached 0.7137. CONCLUSION: Multiplexed MS-PCR is a simple, rapid, accurate and efficient method for SNP typing, which will be very powerful for SNPs in the database establishing of mitochondrial DNA coding regions, the testing of forensic and population genetics research. PMID- 17285548 TI - [The detection of mutations in VHL gene from a single cell in a patient with von Hippel-Lindau disease]. AB - OBJECTIVE: To explore a technology for diagnosing VHL mutations from a single cell and provide experimental evidences for the feasibility of applying technology in detecting genetic mutations from a single cell. METHODS: After whole genome amplification (WGA) based on multiple displacement amplication (MDA) for a single cell, we did regular PCR following sequencing and detected the genotypes using the real time PCR based on TaqMan probes. We detected VHL mutations by the different terminal fluorescent changing. RESULTS: The rate of amplification for single cell based on MDA was 90.91%. The rate of contamination was 0. After sequencing, the allele drop out (ADO) rate of heterozygotes was 26.67%(8/30); combined with the different terminal fluorescent changing, the rate of ADO of heterozygotes was 16.67%. CONCLUSION: WGA based on MDA for a single cell followed by regular PCR with sequencing and real time PCR can specially and accurately detect the VHL genotypes of single cells. PMID- 17285549 TI - [Carrier genetic diagnosis of intron and/or exon-deletion Duchenne muscular dystrophy by microsatellite analysis and quantitative polymerase chain reaction]. AB - OBJECTIVE: To detect the female carriers from the intron and/or exon-deletion Duchenne/Becker musclular dystrophy (DMD) familial members for prenatal or preimplantation genetic diagnosis. METHODS: Using method of PCR to five microsatellite markers (located in 5' terminus and intron 44, 45, 49, 50), analysing of the short tandem repeat sequence polymorphism with the genescan and binding with the quantitative polymerase chain reaction, we detected the DMD carriers from 1 intron and exon -deletion family and 1 intron-deletion family. RESULTS: The STR-50 genotype of II 2 in family 5 was 245/245, so II3 is DMD gene carrier. The STR-45 genotype of II6 and II8 were del/172, III19 was del/178, so they were all DMD gene carriers. CONCLUSION: The STR haploid linkage analysis combined with quantitative polymerase chain reaction is accurate and efficient to detect the female carriers from the intron and/or exon-deletion DMD familial members. PMID- 17285550 TI - [Advancement in the methods for gene dosage analysis]. AB - Gene dosage determination is increasingly important for the study of both genome variation and rearrangement associated with complex diseases. Large genomic duplications and deletions are increasingly found as the causes. Methods such as PCR or sequencing are usually qualitative rather than quantitative. Thus, these methods can not detect large genomic duplications or deletions. Therefore, searching for a gene dosage method which is reliable, sensitive and high throughput becomes imperative. Many high-performance technologies have been developed for gene dosage analyses in the recent years. There are generally three categories of methods including cytogenetic, Southern or dot blotting, or PCR amplification. Recent development in these techniques have been introduced and discussed in this review, which will help people to choose a suitable method for different research. PMID- 17285551 TI - [The clinical application of spectral karyotyping in the analysis of chromosomal abnormalities]. AB - OBJECTIVE: To evaluate value of spectral karyotyping (SKY) in the detection of chromosomal abnormalities. METHODS: A total of 17 metaphase chromosome samples were investigated by SKY, including 10 normal and 5 balanced translocation samples of peripheral blood lymphocytes, one der(Y) sample of peripheral blood lymphocytes and one marker chromosome sample of amniotic fluid cells. The results were compared with those of G-banding diagnosis. RESULTS: Ten normal and 5 balanced translocation samples were diagnosed successfully by SKY in accordance with the results of G-banding; furthermore, SKY analysis revealed that the der(Y) fragment originated from p-arm of chromosome 21 while the marker chromosome originated from chromosome 5. CONCLUSION: SKY is a very sensitive and specific whole genome analysis tool for chromosomal abnormality diagnosis, and exceedingly valuable in the diagnosis on complex chromosomal abnormalities that can not be determined by G-banding. PMID- 17285552 TI - [One family investigation and risk factors analysis of developmental dysplasia of the hip]. AB - OBJECTIVE: To investigate the clinical manifestations and risk factors of the patients from developmental dysplasia of the hip(DDH) family. METHODS: Detailed epidemiology investigation, physical examination, functional movement assessment, lab test and X-ray examination were applied to the whole members of a DDH family. RESULTS: In the family with 9 generations and 218 persons, the incidence of DDH was 31.03% in 145 survivors. Patients mainly manifested bilateral knee and hip joint pain, flexion contracture of hip, limitation in internal and external rotation of hip; a few had arthritic functional disorder, deformation, and limp. The radiography illustrated shallow acetabulum with increased inclination, which encompassed the femoral head badly. Deformation of the femoral head, narrow joint space and osteophyte were also found by X-ray examination. The main risk factors of DDH were genetic factors, gender, birth season etc. The son or daughter with one or two DDH parents had a higher risk for developing DDH than those with no DDH parents. Furthermore, first-degree relatives of the DDH patients also had a greater chance to develop DDH than second-degree relatives and third-degree relatives. The incidence among females was higher than males, and the family member who was given birth in winter had a highest risk for developing DDH. However, there was no difference between incidence of DDH in children and youths and in adults; the incidence of DDH in the immigrants with no blood relationship also did not differ from the incidence of DDH in the family member. CONCLUSION: The genetic factors play an important role in the development of DDH, so do the environmental factors. PMID- 17285553 TI - [Polymorphism of killer cell immunoglobulin-like receptor 2DL3 gene in Zhejiang Han population]. AB - OBJECTIVE: To analyze the allelic polymorphism of killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3) gene in Zhejiang Han population. METHODS: Allelic of KIR2DL3 was detected by PCR sequence based typing (PCR-SBT) method. Two specific fragments of KIR2DL3 were amplified using different primers and sequenced for exons 4,5,7,8,9 of KIR2DL3. All the samples would be assigned to KIR2DL3 allele according to the polymorphism site patterns. RESULTS: Two KIR2DL3 alleles were observed, with KIR2DL3*001 having higher frequency, 0.77. CONCLUSION: The PCR-SBT method is reliable and there are distinctive frequencies of KIR2DL3 alleles in Zhejiang Han population. PMID- 17285555 TI - [Genetic polymorphisms of 14 Y-chromosomal short tandem repeat loci and haplotypes in Tibetan]. AB - OBJECTIVE: To reveal the allelic frequencies and haplotype frequencies of fourteen Y-chromosome short tandem repeat (STR) loci in a Tibetan population. METHODS: The Y-chromosomal STR loci were analyzed from 126 healthy unrelated autochthonous male individuals of Chinese Tibetan using a multiplex PCR system. Allele and haplotype frequencies for these loci were determined by the AmpFISTR Y filer PCR Amplification kit. RESULTS: One hundred and twenty-one alleles were detected from the 14 STR loci. The allele diversity values (DP) for each locus ranged from 0.4104 (DYS391) to 0.9489 (DYS385a, b), the DP value of these loci were higher than 0.5 except for that of DYS391. A total of 105 haplotypes were identified in the Y-STR loci, among which 103 were unique, while two occurred more than once. The overall haplotype diversity for the Y-STR loci was 0.9998, and the discrimination capacity was 0.9898. CONCLUSION: The 14 STR loci above belong to loci of high discriminating ability, the haplotypes are highly polymorphic. PMID- 17285554 TI - [The study on relation of HLA-DRB1 gene polymorphism to Keshan disease and its association and linkage in the core families]. AB - OBJECTIVE: To investigate HLA-DRB1 gene polymorphism in patients with Keshan disease (KD) in the north of China, and its relation to KD in the core families. METHODS: Polymerase chain reaction-sequence specific oligonucleotide probe (PCR SSOP) method was used to determine HLA-DRB1 genotypes in 118 KD patients, including 63 with latent KD and 55 with chronic KD. Sixty-five normal from the same area were selected as controls. The haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) methods were used to analyze the genetic association and linkage of HLA-DRB1 with KD in 18 KD core families. RESULTS: (1) Thirteen kinds of alleles of HLA-DRB1 gene were found in all patients and the controls. (2) The distributive frequency of DR7 allele was significantly lower in chronic KD patients than that in controls (P< 0.01, OR is 0.1695). (3) The distributive frequency of DR7 allele was statistically lower in chronic KD (P< 0.01, OR is 0.091) and showed no differences in latent KD patients as compared with the controls. (4) DR15 allele of HLA-DRB1 gene showed significant association (chi square is 9.32, P< 0.01) and linkage (chi square is 7.40, P< 0.01) with KD patients in the core families. CONCLUSION: The results show that there might be the genetic susceptibility in the pathogenesis of KD. DR7 allele of HLA-DRB1 gene might be the protective gene of KD. Patients with DR7 allele might be more difficult to become to chronic KD. DR15 allele of HLA-DRB1 gene might be linked to the susceptive site of KD. PMID- 17285556 TI - [Polymorphism of fifteen short tandem repeat loci in Maonan minority of Guangxi]. AB - OBJECTIVE: To study the genetic polymorphism of 15 short tandem repeat (STR) (D2S1338i D3S1358i D5S818i D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, CSF1PO, TPOX, TH01, vWA, FGA) in Maonan minority of Guangxi province. METHODS: The allele frequencies and the genotype of 15 STR loci were analyzed in 143 unrelated individuals in Maonan minority of Guangxi by PCR-STR and genescan. RESULTS: There were 130 STR alleles and 390 genotypes in the 15 STR of Maonan minority, with allele frequencies ranging from 0.0035 to 0.5385. The average heterozygosity was 0.7697, the discrimination power was higher than 0.8 except for that of TPOX, the accumulative discrimination power was more than 0.999999999, and the probability of paternity exclusion was more than 0.99999918. CONCLUSION: The 15 STR loci of Maonan minority in Guangxi possesses the characteristics of high genetic diversity, except for the TPOX locus. They can be employed in minority genetics investigation, individual and paternity test in forensic medicine. PMID- 17285557 TI - [Study on the association between the HLA-DRB1 alleles and type 2 diabetes in Yi nationality of Yunnan]. AB - OBJECTIVE: To investigate the association between the polymorphism of HLA-DRB1 alleles and type 2 diabetes mellitus in Yi nationality of Yunnan. METHODS: Polymerase chain reaction-sequence specific primers (PCR-SSP) genotyping method was conducted in 79 patients with type 2 diabetes mellitus and 47 ethnically matched controls in Yi Nationality Autonomous Prefecture, Chuxiong. RESULTS: HLA DR7 and DR11 allele frequencies in type 2 diabetic mellitus patients were significantly higher than those in non-diabetic control subjects respectively(P is 0.009, RR is 8.329;P is 0.029, RR is 7.734). CONCLUSION: DR7 and DR11 alleles are probably susceptible genes of type 2 diabetes mellitus in Yunnan Yi nationality. PMID- 17285558 TI - Modeling hydrogen evolution from the Fe4S4 and Fe8S9X (X = N, C) clusters. Can a Fe--S high-spin cluster serve as a surrogate for the FeMo cofactor? AB - A high-spin model of nitrogenase with a Fe(8)S(9)X(+) cluster (X = nitrogen or carbon) is used to test a mechanism for molecular hydrogen production, which is known to accompany ammonia production. The reaction proceeds with a series of protonation-reduction (PR) steps which are considered to be spontaneous if the calculated hydrogen-cluster bond energy exceeds 35-40 kcal/mol. The novel features of this mechanism include the opening of the cluster when one of the bridging sulfides undergoes two PR steps and the direct participation of the central atom when it undergoes a PR step. After the sixth PR step, a cluster is formed which has a low barrier for loss of molecular hydrogen in an exothermic reaction step. The central atom (nitrogen or carbon) has only a minor effect on the reaction steps. PMID- 17285559 TI - Theoretical study on the Br + CH3SCH3 reaction. AB - The multiple-channel reactions Br + CH(3)SCH(3) --> products are investigated by direct dynamics method. The optimized geometries, frequencies, and minimum energy path are all obtained at the MP2/6-31+G(d,p) level, and energetic information is further refined by the G3(MP2) (single-point) theory. The rate constants for every reaction channels, Br + CH(3)SCH(3) --> CH(3)SCH(2) + HBr (R1), Br + CH(3)SCH(3) --> CH(3)SBr + CH(3) (R2), and Br + CH(3)SCH(3) -->CH(3)S + CH(3)Br (R3), are calculated by canonical variational transition state theory with small curvature tunneling correction over the temperature range 200-3000 K. The total rate constants are in good agreement with the available experimental data, and the two-parameter expression k(T) = 2.68 x 10(-12) exp(-1235.24/T) cm(3)/(molecule s) over the temperature range 200-3000 K is given. Our calculations indicate that hydrogen abstraction channel is the major channel due to the smallest barrier height among three channels considered, and the other two channels to yield CH(3)SBr + CH(3) and CH(3)S + CH(3)Br are minor channels over the whole temperature range. PMID- 17285560 TI - Maintaining solvent accessible surface area under rotamer substitution for protein design. AB - Although quantities derived from solvent accessible surface areas (SASA) are useful in many applications in protein design and structural biology, the computational cost of accurate SASA calculation makes SASA-based scores difficult to integrate into commonly used protein design methodologies. We demonstrate a method for maintaining accurate SASA during a Monte Carlo search of sequence and rotamer space for a fixed protein backbone. We extend the fast Le Grand and Merz algorithm (Le Grand and Merz, J Comput Chem, 14, 349), which discretizes the solvent accessible surface for each atom by placing dots on a sphere and combines Boolean masks to determine which dots are exposed. By replacing semigroup operations with group operations (from Boolean logic to counting dot coverage) we support SASA updates. Our algorithm takes time proportional to the number of atoms affected by rotamer substitution, rather than the number of atoms in the protein. For design simulations with a one hundred residue protein our approach is approximately 145 times faster than performing a Le Grand and Merz SASA calculation from scratch following each rotamer substitution. To demonstrate practical effectiveness, we optimize a SASA-based measure of protein packing in the complete redesign of a large set of proteins and protein-protein interfaces. PMID- 17285561 TI - WI-PHI: a weighted yeast interactome enriched for direct physical interactions. AB - How is the yeast proteome wired? This important question, central in yeast systems biology, remains unanswered in spite of the abundance of protein interaction data from high-throughput experiments. Unfortunately, these large scale studies show striking discrepancies in their results and coverage such that biologists scrutinizing the "interactome" are often confounded by a mix of established physical interactions, functional associations, and experimental artifacts. This stimulated early attempts to integrate the available information and produce a list of protein interactions ranked according to an estimated functional reliability. The recent publication of the results of two large protein interaction experiments and the completion of a comprehensive literature curation effort has more than doubled the available information on the wiring of the yeast proteome. This motivates a fresh approach to the compilation of a yeast interactome based purely on evidence of physical interaction. We present a procedure exploiting both heuristic and probabilistic strategies to draft the yeast interactome taking advantage of various heterogeneous data sources: application of tandem affinity purification coupled to MS (TAP-MS), large-scale yeast two-hybrid studies, and results of small-scale experiments stored in dedicated databases. The end result is WI-PHI, a weighted network encompassing a large majority of yeast proteins. PMID- 17285562 TI - Is the intrinsic disorder of proteins the cause of the scale-free architecture of protein-protein interaction networks? AB - In protein-protein interaction (PPI) networks certain topological properties appear to be recurrent: network maps are considered scale-free. It is possible that this topology is reflected in the protein structure. In this paper, we investigate the role of protein disorder in the network topology. We find that the disorder of a protein (or of its neighbors) is independent of its number of PPIs. This result suggests that protein disorder does not play a role in the scale-free architecture of protein networks. PMID- 17285563 TI - Proteomic analysis of the oxidative stress response in Candida albicans. AB - An efficient oxidative stress response (OSR) is important for the facultative pathogenic yeast Candida albicans to survive within the human host. We used a large scale 2-D protein gel electrophoresis approach to analyze the stress response mechanisms of C. albicans after treatment with hydrogen peroxide and the thiol oxidizing agent, diamide. Quantitation of in vivo protein synthesis after pulse labeling of the proteins with radioactive L-[35S]-methionine resulted in characteristic proteome signatures for hydrogen peroxide and diamide with significant overlap of 21 up-regulated proteins for both stressors. Among the induced proteins were enzymes with known antioxidant functions like catalase or thioredoxin reductase and a set of oxidoreductases. 2-D gel analysis of mutants in the CAP1 gene revealed that the synthesis of 12 proteins is controlled by the oxidative stress regulator Cap1p. Stressing its importance for the C. albicans OSR, all 12 proteins were also induced after oxidative challenge by hydrogen peroxide or diamide. PMID- 17285564 TI - 15N-metabolic labeling for comparative plasma membrane proteomics in Arabidopsis cells. AB - An important goal for proteomic studies is the global comparison of proteomes from different genotypes, tissues, or physiological conditions. This has so far been mostly achieved by densitometric comparison of spot intensities after protein separation by 2-DE. However, the physicochemical properties of membrane proteins preclude the use of 2-DE. Here, we describe the use of in vivo labeling by the stable isotope 15N as an alternative approach for comparative membrane proteomic studies in plant cells. We confirm that 15N-metabolic labeling of proteins is possible and efficient in Arabidopsis suspension cells. Quantification of 14N versus 15N MS signals reflects the relative abundance of 14N and 15N proteins in the sample analyzed. We describe the use of 15N-metabolic labeling to perform a partial comparative analysis of Arabidopsis cells following cadmium exposure. By focusing our attention on plasma membrane proteins, we were able to confidently identify proteins showing up to 5-fold regulation compared to unexposed cells. This study provides a proof of principle that 15N-metabolic labeling is a useful technique for comparative membrane proteome studies. PMID- 17285565 TI - Estimation of the membrane permeability of liposomes via use of eosin Y chemiluminescence catalysed by peroxidase encapsulated in liposomes. AB - The initial rate of horseradish peroxidase (HRP)-catalysed chemiluminescence (CL) reaction in an aqueous compartment of liposomes was applied to the estimation of membrane permeability of liposomes. HRP-encapsulated liposomes were prepared by an extrusion method, and a CL reagent and H(2)O(2) were added into the liposomes suspensions. Fluorescein, eosin Y and phloxin B, which are xanthene dyes with different chemical structures, were used as CL reagents. Xanthene dye and H(2)O(2) permeate into the inner phase of liposomes, resulting in initiation of the HRP-catalysed xanthene dye CL reaction with H(2)O(2). The initial rate of the CL reaction was independent of the xanthene dye used. The reproducibility of the initial rate with eosin Y was better than that with fluorescein and phloxin B. When the membrane permeability of the liposomes was changed by altering the concentration of cholesterol in them, the initial rate of the eosin Y CL reaction was dependent on the membrane permeability of the liposomes. PMID- 17285566 TI - Glowworms: a review of Arachnocampa spp. and kin. AB - The term 'glowworm' is used in connection with the flightless females of lampyrid fireflies and to describe the luminescent larvae of certain fungus gnats that belong to the subfamilies Arachnocampinae, Keroplatinae and Macrocerinae of the dipteran family Keroplatidae. This review focuses on the luminescent larval fungus gnats. The weakly luminescent species of the Holarctic feed mainly on fungal spores, but some, such as Orfelia fultoni, have turned to a carnivorous diet. Larval Australian and New Zealand Arachnocampa spp. produce brighter in vivo (but not necessarily in vitro) lights, live in cool, damp and dark places and are exclusively predatory. They lure their prey (usually small flying insects) with the help of their blue-green light emissions towards snares consisting of vertical silk threads coated with sticky mucus droplets. Fungus gnats with similar 'fishing lines' are found in the Neotropics, but they are not luminescent. The larval stage is longest in the life cycle of Arachnocampa, lasting up to a year, depending on climatic conditions such as temperature and humidity as well as food supply. In A. luminosa, but not the Australian A. flava, female pupae and even female imagines are luminescent. However, it remains to be demonstrated whether it is the light of the female, a pheromone or both that attract the males. Light organs and the chemical reactions to produce light differ between the holarctic and the Australian/New Zealand species. Prey is attracted only by the glowworm's light; odours of the fishing lines or the glowworms themselves are not involved. Recognition of the prey by the glowworm involves mechano- and chemoreception. The eyes of both larval and adult glowworms are large and functional over a spectral range covering UV to green wavelengths. Adults are poor fliers, live only for a few days, have degenerate mouth parts and do not feed. Maintenance of glowworms in captivity is possible and the impact of tourism on glowworms in natural settings can be minimized through appropriate precautions. PMID- 17285567 TI - Chemiluminescence assay for tetrahydrobiopterin based on the generation of hydrogen peroxide using isoluminol-microperoxidase in the presence of 1-methoxy PMS. AB - We developed a novel highly sensitive chemiluminescence (CL) method for BH(4). The principle of the proposed method is based on active oxygen formation induced by 1-methoxy-5-methyl phenazinium methyl sulphate (1-methoxy PMS) in the presence of dissolved oxygen. Furthermore, active oxygen is determined by a CL assay involving the luminol reaction with microperoxidase. In this report, we examined the mechanism of formation and identified the reactive oxygen species derived from BH(4) employing 1-methoxy PMS. Additionally, optimum conditions for the CL assay of BH(4) were established. PMID- 17285568 TI - Bioluminescent assay of total bacterial contamination of drinking water. AB - A bioluminescent assay of total bacterial contamination (TBC) of drinking water (DW) with a detection limit of approximately 1 CFU/mL and duration of less than 7 h has been developed. The protocol of the TBC assay comprises: incubation of water sample in nutrition broth supplemented with salts mixture, up to 6 h; filtration of bacterial suspension obtained through membrane filter (pore size 0.45 microm); release of bacterial ATP by dimethyl sulphoxide; determination of bacterial ATP concentration using highly sensitive ATP reagent based on recombinant Luciola mingrelica luciferase. To simplify the assay, special luminometer microcuvette Filtravette (New Horizons Diagnostics Corp., USA) are used. A good correlation (R=0.98) between ATP concentration measured after 6 h incubation and initial bacterial titre in DW was observed. Semi-quantitative TBC assay of DW is also available. The TBC value in DW is assessed by the fixation of incubation time required to detect a measurable bioluminescent signal: 3, 4 and 6 h corresponds to 100-1000, 10-100 and 1-10 CFU/mL, respectively. PMID- 17285569 TI - Enhanced inflammatory response to coronary stenting marks the development of clinically relevant restenosis. AB - OBJECTIVES: The aims of this study were to investigate the effect of coronary stenting on the release of cytokines and cell-mediated immunity factors and to evaluate the association between inflammation and clinical outcomes at 6 months. BACKGROUND: Circulating levels of inflammatory markers and cytokines are elevated in patients with acute coronary syndromes and are related to an unfavorable outcome. The aims of this study were to investigate the effect of coronary stenting on the release of cytokines and cell-mediated immunity factors and to evaluate the association between inflammation and clinical outcomes at 6 months. METHODS: Forty patients with single native coronary artery disease treated with stenting were enrolled. Peripheral venous blood samples were collected before and 6 h, 48 h, and 12 weeks after stenting. Serum concentrations of high-sensitivity C-reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-alpha (markers of inflammation) and serum-soluble interleukin-2 receptor for T lymphocyte activation (sIL2-R, marker of cell-mediated immunity) were measured. Patients also were evaluated clinically one, 3, and 6 months post-stenting or when they presented with cardiovascular symptoms to identify major adverse cardiac events (cardiac death, MI, revascularization). RESULTS: Concentrations of interleukins 6 and 8 and tumor necrosis factor-alpha peaked at 6 h (11.0, 12.6, and 5.3 pg/ml, respectively). The peak level of high-sensitivity C-reactive protein (2.77 mg/dL) occurred 48 h post stenting, while sIL2-R peaked (495 U/ml) at 12 weeks. Patients who experienced restenosis had higher levels of C-reactive protein at 48 h (4.94 vs. 1.84 mg/dl; P = 0.043) and of IL-8 at 6 h (26.75 vs. 13.55 pg/mL; P = 0.048) than those without restenosis. CONCLUSIONS: Proinflammatory cytokines and inflammatory markers are released into the peripheral circulation early after coronary stenting, and increased levels of some are associated with clinically relevant restenosis. PMID- 17285570 TI - Development of functional imidazole derivatives: the influence of alkaline metal cations on the rates of CL reactions of 2-(phenyl and 4-dimethylaminophenyl)-4 hydroperoxy-4-3',4'-(15-crown-5)phenyl-5-3''-4''-(15-crown-5)phenyl-4H isoimidazoles. AB - Although several investigations have focused on luminescence modulation by chelation with metal cations using bidentate ligands or crown ether systems, a bis(crown ether) system has not yet been used for modulation of chemiluminescence (CL) reactions. In the CL reaction of 2-(phenyl and 4-dimethylaminophenyl)-4 hydroperoxy-4-3',4'-(15-crown-5)phenyl-5-3'',4''(15-crown-5)phenyl-4H isoimidazoles 2a and b possessing a bis(15-crown-5 ether) moiety, the rate acceleration was observed in the presence of K(+), Rb(+) and Cs(+) due to the holding effect of the bis-crown moiety, but no rate acceleration was observed by Li(+) and Na(+) due to the template effect of the crown moiety. The acceleration of the CL reaction rates is ascribable to the conformational change induced by the scissor-like motion of the bis-crown moiety assisted by the holding effect. PMID- 17285571 TI - Meta-analysis of mixed treatment comparisons at multiple follow-up times. AB - Mixed treatment comparisons (MTC) meta-analysis is a methodology for making inferences on relative treatment effects based on a synthesis of both direct and indirect evidence on multiple treatment contrasts. This is particularly useful in the context of cost-effectiveness analysis and medical decision making. Here, we extend these methods to a more complex situation where trials report results at one or more, different yet fixed, follow-up times. These methods are applied to an illustrative data set combining evidence on healing rates under six different treatments for gastro-esophageal reflux disease (GERD). A series of Bayesian hierarchical models based on piece-wise exponential hazards is developed that borrow strength across the MTC networks and also across time points. These include models for absolute and relative treatment effects, models with fixed or random effects over time, random walk models, and models with homogeneous or heterogeneous between-trials variation. The deviance information criterion (DIC) is used to guide model development and selection. Models for absolute treatment effects generate materially different rankings of the treatments than models that separate the trial-specific baselines from the relative treatment effects. The extent of between-trials heterogeneity in treatment effects depends on treatment contrast. In discussion we note that models of this type have a very wide potential application. PMID- 17285572 TI - Characterization of t(6;11)(p21;q12) in a renal-cell carcinoma of an adult patient. AB - Renal-cell carcinoma (RCC) constitutes a heterogeneous group of tumors with specific chromosome aberrations. Recently, a new small group of RCC, occurring in children and young adults, has been described as characterized by t(6;11)(p21;q12). It has been shown that this translocation results in the fusion of the 5' portion of the ALPHA gene (11q12) with the transcription factor gene TFEB (6p21). Herewith, we report the first complete cytogenetic and molecular characterization of a t(6;11)-positive RCC of an adult patient, a 54-year-old woman. The tumor was histologically defined as RCC with peculiar features and it was negative for epithelial markers and positive for melanocytic markers. Chromosome QFQ banding analysis of short-term cultured cells from the RCC showed t(6;11)(p21;q12) as the sole cytogenetic abnormality. The translocation was confirmed by FISH analysis. RT-PCR analysis, performed on total RNA isolated from both neoplastic and normal tissue samples, revealed an ALPHA-TFEB chimeric transcript in the tumor sample; sequencing of the RT-PCR product defined a novel TFEB gene breakpoint cluster region, broader than the one reported thus far. Western blot analysis showed a band at the expected size of wild-type TFEB in the neoplastic tissue compared to the normal sample, supporting that the fusion gene does not encode for a chimeric protein but it causes an upregulation of the wild type TFEB. Our data contribute to define better this rare RCC type, which is typical not only of childhood but can also be found in adulthood. PMID- 17285573 TI - Nonrandom pattern of chromosome aberrations in 17beta-estradiol-induced rat mammary tumors: indications of distinct pathways for tumor development. AB - Estrogens play an important role in breast cancer etiology and the ACI rat provides a novel animal model for defining the mechanisms through which estrogens contribute to mammary cancer development. In crossing experiments between the susceptible ACI strain and two resistant strains, COP (Copenhagen) and BN (Brown Norway), several quantitative trait loci (QTL) that affect development of 17beta estradiol (E2)-induced mammary tumors have been defined. Using comparative genomic hybridization (CGH), we have analyzed cytogenetic aberrations in E2 induced mammary cancers and have found clear patterns of nonrandom chromosomal involvement. Approximately two thirds of the tumors exhibited copy number changes. Losses of rat chromosome 5 (RNO5) and RNO20 were particularly common, and it was found that these two aberrations often occurred together. A third recurrent aberration involving proximal gain and distal loss in RNO6 probably defined a distinct subgroup of tumors, since it never occurred in combination with RNO5 loss. Interestingly, QTL with powerful effects on mammary cancer development have been mapped to RNO5 and RNO6. These findings suggest that there were at least two genetic pathways to tumor formation in this rat model of E2 induced mammary cancer. By performing CGH on mammary tumors from ACI rats, F1 rats from crosses between the ACI and COP or BN strains and ACI.BN-Emca8 congenic rats, which carry the BN allele of the Emca8 QTL on RNO5 on the ACI genetic background, we were able to determine that the constitution of the germ line influences the pattern of chromosomal aberrations. PMID- 17285574 TI - Co-amplification of 8p12 and 11q13 in breast cancers is not the result of a single genomic event. AB - Epithelial cancers frequently have multiple amplifications, and particular amplicons tend to occur together. These co-amplifications have been suggested to result from amplification of pre-existing junctions between two chromosomes, that is, translocation junctions. We investigated this hypothesis for two amplifications frequent in breast cancer, at 8p12 and 11q13, which had been reported to be associated in Southern blot studies. We confirmed that both genomic amplification and expression of genes was correlated between the frequently-amplified regions of 8p and 11q, in array CGH and microarray expression data, supporting the importance of co-amplification. We examined by FISH the physical structure of co-amplifications that we had identified by array CGH, in five breast cancer cell lines (HCC1500, MDA-MB-134, MDA-MB-175, SUM44, and ZR-75-1), four breast tumors, and a pancreatic cancer cell line (SUIT2). We found a variety of arrangements: amplification of translocation junctions; entirely independent amplification of the two regions on separate chromosomes; and separate amplification of 8p and 11q sequences in distinct sites on the same rearranged chromosome. In this last arrangement, interphase nuclei often showed intermingling of FISH signals from 8p12 and 11q13, giving a false impression that the sequences were interdigitated. We conclude that co-amplification of the main 8p and 11q amplicons in breast tumors is not usually the result of a preceding translocation event but most likely reflects selection of clones that have amplified both loci. This article contains supplementary material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. PMID- 17285575 TI - Definition of a minimal region of deletion of chromosome 7 in uterine leiomyomas by tiling-path microarray CGH and mutation analysis of known genes in this region. AB - Somatic interstitial deletions of chromosome segment 7q22-q31 in uterine leiomyomas are a frequent event, thought to be indicative of a tumor suppressor gene in the region. Previous LOH and CGH studies have refined this region to 7q22.3-q31, although the target gene has not been identified. Here, we have used tiling-path resolution microarray CGH to further refine the region and to identify homozygous deletions in fibroids. Furthermore, we have screened all manually annotated genes in the region for mutations. We have refined the minimum deleted region at 7q22.3-q31 to 2.79 Mbp and identified a second region of deletion at 7q34. However, we identified no pathogenic coding variation. PMID- 17285576 TI - Cytogenetic patterns in ETV6/RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia: A Nordic series of 245 cases and review of the literature. AB - Between 1992 and 2004, 1,140 children (1 to<15 years) were diagnosed with B-cell precursor acute lymphoblastic leukemia (ALL) in the Nordic countries. Of these, 288 (25%) were positive for t(12;21)(p13;q22) [ETV6/RUNX1]. G-banding analyses were successful in 245 (85%); 43 (15%) were karyotypic failures. The modal chromosome numbers, incidence, types, and numbers of additional abnormalities, genomic imbalances, and chromosomal breakpoints in the 245 karyotypically informative cases, as well as in 152 previously reported cytogenetically characterized t(12;21)-positive ALLs in the same age group, were ascertained. The most common modal numbers among the 397 cases were 46 (67%), 47 (16%), 48 (6%), and 45 (5%). High-hyperdiploidy, triploidy, and tetraploidy were each found in approximately 1%; none had less than 40 chromosomes. Secondary chromosomal abnormalities were identified by chromosome banding in 248 (62%) of the 397 ALLs. Of these, 172 (69%) displayed only unbalanced changes, 14 (6%) only balanced aberrations, and 26 (10%) harbored both unbalanced and balanced abnormalities; 36 (15%) were uninformative because of incomplete karyotypes. The numbers of secondary changes varied between 1 and 19, with a median of 2 additional aberrations per cytogenetically abnormal case. The most frequent genomic imbalances were deletions of 6q21-27 (18%), 8p11-23 (6%), 9p13-24 (7%), 11q23-25 (6%), 12p11-13 (27%), 13q14-34 (7%), loss of the X chromosome (8%), and gains of 10 (9%), 16 (6%), and 21 (29%); no frequent partial gains were noted. The chromosome bands most often involved in structural rearrangements were 3p21 (2%), 5q13 (2%), 6q12 (2%), 6q14 (2%), 6q16 (2%), 6q21 (10%), 6q23 (6%), 6q25 (3%), 9p13 (2%), 11q13 (2%), 11q23 (2%), 12p11 (6%), 12p12 (7%), 12p13 (25%), 21q10 (6%), and 21q22 (6%). Considering that the t(12;21) is known to arise in utero and that the postnatal latency period is protracted, additional mutations are most likely necessary for overt ALL. The frequently rearranged chromosome regions may harbor genes of importance for the transformation and/or progression of an initial preleukemic t(12;21)-positive clone. PMID- 17285577 TI - Parameters of bladder function in pre-, peri-, and postmenopausal continent women without detrusor overactivity. AB - AIMS: To determine normative data for lower urinary tract function in asymptomatic continent women without detrusor overactivity (DO) across the age span. METHODS: Healthy female volunteers aged > or =20 years were recruited from the community. Comprehensive assessment included bladder diary, physical examination, uroflowmetry, and video-urodynamics. Continent women without history of frequent urgency and without DO were selected. Data on bladder storage, voiding and urethral sphincter function, urine output and frequency are presented for pre-, peri-, and postmenopausal women. RESULTS: Twenty-four asymptomatic women (mean age 50.2 years, range 22-80 years) met the inclusion criteria, including 7 pre- (29.2 years), 7 peri- (48.8 years), and 10 postmenopausal (66.0 years) women. For all subjects, maximum single voided volume in bladder diary was 500 ml and maximum cystometric capacity was 580 ml (median values). Strong desire to void (SDV) was reported at 287, 366, and 425 ml for pre-, peri-, and postmenopausal groups, respectively. The maximum flow rate was 25, 32, and 23 ml/sec in uroflowmetry and 23, 24, and 18 ml/sec in pressure-flow study, respectively. Median post-void residual volume (PVR) was below 20 ml in all groups. At maximum flow rate subjects voided with detrusor pressures of 29, 26, and 24 cm H(2)O, respectively. Maximum urethral closure pressure was 94, 74, and 42 cm H(2)O, respectively. CONCLUSIONS: We provide normative data on bladder function in asymptomatic, continent, pre-, peri-, and postmenopausal women without DO. PMID- 17285578 TI - Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition. AB - We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, to examine the associations between prediagnostic serum concentrations of C-peptide, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-2, and endometrial cancer risk. Among pre- and post-menopausal women, who were not currently using exogenous hormones, 286 women developed incident endometrial cancer during an average 5.1 years follow up. Using risk set sampling, 555 matched control subjects were selected. In conditional logistic regression models adjusted for matching factors only, endometrial cancer risk increased with increasing serum levels of C-peptide (relative risks (RR) for the top vs. bottom quartile = 2.13 [95% confidence interval (CI) 1.33-3.41], p(trend) = 0.001, and decreasing serum levels of IGFBP 2 (RR for the top vs. bottom quartile = 0.56 [95% CI 0.35-0.90], p(trend) = 0.03, but was not significantly associated with IGFBP-1 levels (RR for the top vs. bottom quartile = 0.76 [95% CI 0.47-1.21], p(trend) = 0.25). In BMI-adjusted models, only the C-peptide association remained marginally statistically significant (RR for the top vs. bottom quartile = 1.56 [95% CI 0.94-2.57], p(trend) = 0.05 for C-peptide; 0.84 [95% CI 0.50-1.40], p(trend) = 0.74 for IGFBP 2; and 1.08 [95% CI 0.65-1.78], p(trend) = 0.86 for IGFBP-1 levels). These associations were stronger among nonfasting women (< or =< or =6 hr since last meal; 63% of subjects) but were not evident among fasting women, although the interactions were not statistically significant. The C-peptide-risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women (RR for the top vs. bottom quartile = 1.28 [95% CI 0.67 2.45], p(trend) = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer. PMID- 17285580 TI - Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors. AB - Deletions on chromosomes 1p and 19q are associated with favorable prognosis in patients with oligodendroglial tumors. The aim of our study was to identify additional genomic aberrations linked to patient survival. We performed a genome wide screen for genomic imbalances by comparative genomic hybridization on tumors from 70 patients, including 40 oligodendrogliomas, 30 oligoastrocytomas (21 WHO grade II tumors, 49 WHO grade III tumors). Data were correlated with overall patient survival (OS, median follow-up: 5.8 years). The most frequent aberrations were losses on chromosome 19q (64%), 1p (59%), 9p (26%), 4q (21%), 10q (19%), 18q (17%); gains on 7q (24%), 19p (19%), 7p (17%). In univariate analyses, combined 1p/19q and 19q loss were significantly associated with longer OS, and gains on 7, 8q, 19q, 20, losses on 9p, 10, 18q, Xp with shorter OS. Multivariate analyses showed the most significant prognostic factors for OS of patients with any oligodendroglial tumor to be WHO grade [odds ratio (OR) 8], 7p gain (OR 6), 9p loss (OR 3); for OS of patients with anaplastic tumors to be 7p gain (OR 10), 8q gain (OR 5), 18q loss (OR 3). Patients with anaplastic oligodendroglial tumors containing one or more prognostically unfavorable genomic aberration had a poor outcome independent of the 1p/19q status. In summary, we identified several independent genomic markers of shorter survival in patients with oligodendroglial tumors. Thus, molecular diagnostic testing, which is usually restricted to 1p/19q deletion analysis, may need to be refined by additionally assessing the prognostically unfavorable genomic aberrations identified. PMID- 17285579 TI - Aberrant promoter methylation in pleural fluid DNA for diagnosis of malignant pleural effusion. AB - Accumulating evidence implicates epigenetic changes such as hypermethylation in carcinogenesis. We investigated whether DNA methylation of 5 tumor suppressor genes in pleural fluid samples could aid in diagnosis of malignant effusion. In samples from 47 patients with malignant pleural effusions and 34 with nonmalignant effusions, we used a methylation-specific polymerase chain reaction to detect aberrant hypermethylation of the promoters of the DNA repair gene O(6) methylguanine-DNA methyltransferase (MGMT), p16(INK4a), ras association domain family 1A (RASSF1A), apoptosis-related genes, death-associated protein kinase (DAPK), and retinoic acid receptor beta (RARbeta). Promoter hypermethylation was associated with malignant effusion for MGMT (Odds ratio (OR) = infinity), p16(INK4a) (OR = infinity), RASSF1A (OR = 13.8; CI, 1.71-112), and RARbeta (OR = 3.17; CI, 1.10-9.11), but not for DAPK. Instead, DAPK methylation was associated with the length of smoking (p < 0.05). Patients with hypermethylation of MGMT, p16(INK4a), RASSF1A or RARbeta were 5.68 times more likely to have malignant effusions than patients without methylation (p = 0.008). Methylations per patient were more numerous for lung cancer than nonmalignant pulmonary disease (0.915 vs. 0.206, p < 0.001). Sensitivity, specificity, and positive predictive value of methylation in one or more genes for diagnosis of malignant effusion were 59.6%, 79.4%, and 80.0% respectively. In conclusion, aberrant promoter methylation of tumor suppressor genes in pleural fluid DNA could be a valuable diagnostic marker for malignant pleural effusion. PMID- 17285581 TI - Towards a ligand targeted enzyme prodrug therapy: single round panning of a beta lactamase scaffold library on human cancer cells. AB - A novel beta-lactamase scaffold library in which the target-binding moiety is built into the enzyme was generated using phage display technology. The binding element is composed of a fully randomized 8 amino acid loop inserted at position between Y34 and K37 on the outer surface of Enterobacter cloacae P99 cephalosporinase (beta-lactamase, E.C. 3.5.2.6) with all library members retaining catalytic activity. The frequency and diversity of amino acids distributions in peptide inserts from library clones were analyzed. The complexity of the randomized loop appears consistent with standards of other types of phage display library systems. The library was panned against SKBR3 human breast cancer cells in 1 round using rolling circle amplification of phage DNA to recover bound phage. Individual beta-lactamase clones, independent of phage, were rapidly assessed for their binding to SKBR3 cells using a simple high throughput screen based on cell-bound beta-lactamase activity. SKBR3 cell-binding beta-lactamase enzymes were also shown to bind specifically using an immunochemical method. Selected beta-lactamase clones were further studied for their protein expression, enzyme activity and binding to nontumor cell-lines. Overall, the approach outlined here offers the opportunity of rapidly selecting targeted beta-lactamase ligands that may have a potential for their use in enzyme prodrug therapy with cephalosporin-based prodrugs. It is expected that a similar approach will be useful in developing tumor-targeting molecules of several other enzyme candidates of cancer prodrug therapy. PMID- 17285582 TI - A wide difference in cancer survival between middle aged and elderly patients in Europe. AB - Nowadays the burden of cancer in elderly people has reached an alarming extent. The purpose of this study is comparing cumulative and conditional relative survival in elderly patients between 65 and 84 years and younger adults aged from 55 to 64. Fifty-three cancer registries of 22 European countries, participating in the EUROCARE-3 programme, collected information on the cases diagnosed over the period 1990-1994. We computed cumulative and conditional relative survival for 16 cancer sites. Middle aged patients experienced a better prognosis than the elderly for all cancer sites, in both sexes and the differences were more marked at 1 than 5 years since diagnosis. The very large differences noted in the first period after cancer detection declined in the subsequent years and, when 5-years conditional survival was considered, for several cancers the elderly and younger adults had the same probabilities of surviving. The death relative excess risks (RERs) in the elderly with respect younger individuals were really very high and markedly larger at 1 than 5 years, and in women than men. Genitourinary and gynaecological cancers showed the highest RERs, around 2.0 and between 1.5 and 2.5 respectively. This very high early mortality could be due not only to clinical aspects: the barriers to health care access and a consequent late diagnosis might represent for elderly patients the main determinant of this very large prognostic disadvantage. In conclusion, clinical management of cancer in the elderly remains a major issue to be faced with complex social and health care policies. PMID- 17285583 TI - Attribution of blame to rape victims among therapists and non-therapists. AB - This paper examines the hypothesis of modular judgment in the context of attribution of blame to rape victims. Modular judgment was operationalized using blame schemata suited to judgment of everyday aggression. Subjects were 72 individuals, 36 therapists and 36 non-therapists; half were men and half women. Each subject was presented with written descriptions of four rapes, which included information regarding victim's gender (male versus female) and victim's prior acquaintance with the rapist (stranger or known). Dependent variables were attribution of blame and judgments regarding severity of the rape and of the punishment deserved by the rapist. Among both therapists and non-therapists there was a slight general tendency to blame the victim. As expected, women were blamed more than men. Also, men attributed less blame to male victims then did women, whereas women attributed less blame to female victims then did men. These results support the theories of modular judgment and of defensive attribution. As for judgment of severity of the rape, therapists judged the rapes as slightly more severe. Similar results were found regarding judgment of deserved punishment. We suggest further investigation of the connection between blame attribution and rape myths, which may facilitate blaming the victim. PMID- 17285584 TI - The impact of death qualification, belief in a just world, legal authoritarianism, and locus of control on venirepersons' evaluations of aggravating and mitigating circumstances in capital trials. AB - The purpose of this study was to investigate the impact of death qualification, belief in a just world (BJW), legal authoritarianism (RLAQ), and locus of control (LOC) on venirepersons' evaluations of aggravating and mitigating circumstances in capital trials. 212 venirepersons from the 12th Judicial Circuit in Bradenton, FL, completed a booklet that contained the following: one question that measured their attitudes toward the death penalty; one question that categorized their death-qualification status; the BJW, LOC, and RLAQ scales; a summary of the guilt and penalty phases of a capital case; a 26-item measure that required participants to evaluate aggravators, nonstatutory mitigators, and statutory mitigators on a 6-point Likert scale; sentence preference; and standard demographic questions. Results indicated that death-qualified venirepersons were more likely to demonstrate higher endorsements of aggravating factors and lower endorsements of both nonstatutory and statutory mitigating factors. Death qualified participants were also more likely to have a high belief in a just world, espouse legal authoritarian beliefs, and exhibit an internal locus of control. Findings also suggested that venirepersons with a low belief in a just world and an external locus of control demonstrated higher endorsements of statutory mitigators. Participants with legal authoritarian beliefs revealed higher endorsements of aggravators and lower endorsements of nonstatutory mitigators. Legal implications and applications are discussed. PMID- 17285585 TI - Adjudicative competence and comprehension of Miranda rights in adolescent defendants: a comparison of legal standards. AB - Currently, there is considerable variability and ambiguity in legal standards pertaining to juveniles' comprehension of Miranda rights and their adjudicative competence. This study investigated rates of impairment under various proposed legal standards. One hundred and fifty-two young defendants aged 11-17 were assessed with Grisso's Miranda Instruments and the Fitness Interview Test Revised. While over half of defendants aged 15 and under were classified as impaired in adjudicative capacities when adult norms were applied, significantly fewer adolescents were classified as impaired when adolescent norms were applied or a standard of "basic understanding and communication." Also, while over half of defendants aged 15 and under were classified as impaired in their comprehension of Miranda rights when both understanding and appreciation of Miranda rights were required, significantly fewer youth were classified as being impaired when only understanding was required. The implications of these findings are discussed. PMID- 17285586 TI - Are release recommendations for NGRI acquittees informed by relevant data? AB - We conducted a retrospective review of factors involved in clinical recommendations for release of patients adjudicated not guilty by reason of insanity (NGRI). Medical records from 91 patients in a maximum security forensic hospital who participated in a formal hearing process to determine suitability for release were reviewed. The purpose of the study was twofold: (1) to examine the process involved in day to day clinical decision-making regarding release from a maximum security forensic hospital and (2) to determine what factors in a patient's clinical and legal history were related to recommendation decisions. Multivariate statistical methods revealed that among the clinical, demographic, and legal information available to clinicians at the time a formal release recommendation was made two factors emerged that were significantly related to release recommendations: PCL-R score and the age at which the patient committed his first criminal offense. Patients with high levels of psychopathy and those who engaged in criminal behavior at a younger age were less likely to be recommended for release from a maximum security forensic hospital. PMID- 17285587 TI - In situ diagnostics of the decomposition of silacyclobutane on a hot filament by vacuum ultraviolet laser ionization mass spectrometry. AB - The gas-phase reaction products of silacyclobutane (SCB) and 1, 1-dideuterio silacyclobutane (SCB-d(2)) from a hot-wire chemical vapor deposition (HWCVD) chamber were diagnosed in situ using vacuum ultraviolet (VUV) laser single-photon ionization (SPI) coupled with time-of-flight (TOF) mass spectrometry. The SCB molecule was found to decompose at a filament temperature as low as 900 degrees C. Both Si- (silylene, methylsilylene, and silene) and C-containing (ethene and propene) species were produced from the SCB decomposition on the filament. Ethene and propene were detected by the mass spectrometer. It is demonstrated that the formation of ethene is favored over that of propene. The experimental study of hot-wire decomposition of SCB-d(2) shows that propene is most likely produced by a process that is initiated by a 1,2-H(D) migration to form n-propylsilylene, followed by an equilibration with silacyclopropane, which then decomposes to propene. The detection of ethene in our experiment indicates that a competitive route of fragmentation exists for SCB decomposition on the filament. It has been shown that this competitive route occurs without H/D scrambling. The highly reactive silylene, silene, and methylsilylene species produced from SCB decomposition underwent either insertion reactions into the Si-H bonds of the parent molecule or pi-type addition reaction across the double and triple CC bonds. The dimerization product of silene, 1,3-disilacyclobutane, at m/z = 88 was also observed. PMID- 17285588 TI - Solution structures and biological functions of the antimicrobial peptide, arenicin-1, and its linear derivative. AB - Arenicin-1 (AR-1) is a novel antimicrobial peptide that was isolated from coelomocytes of the marine polychaeta lugworm Arenicola marina and shown to contain a single disulfide bond between Cys3 and Cys20, forming an 18-residue ring [Ovchinnikova, T. V. et al., FEBS Lett 2004, 577, 209-214]. To determine the role of this disulfide bond, we synthesized AR-1 (RWCVYAYVRVRGVLVRYRRCW) and its linear derivative, arenicin-1-S (AR-1-S: RWSVYAYVRVRGVLVRYRRSW). Activity assays revealed that AR-1-S is somewhat less active against bacterial cells than AR-1. Both peptides were very hydrophobic, and displayed cytotoxicity against human red blood cells. Analysis of the tertiary structures of AR-1 and AR-1-S by NMR spectroscopy disclosed that AR-1 has two-stranded antiparallel beta-sheet structures with amphipathicity, while AR-1-S displays a random coil structure in DMSO. Our biological data for AR-1 and AR-1-S indicate that the hydrophobic hydrophilic balance, disulfide bridge, and the amphipathic beta-sheet structure of the peptides play important roles in their biological activities. Elucidation of the structure of AR-1 and its derivative should facilitate the design of novel non-cytotoxic peptide antibiotics with potent antibacterial activities. PMID- 17285589 TI - Identification of genes preferentially expressed by microglia and upregulated during cuprizone-induced inflammation. AB - Microglia, monocytes, and peripheral macrophages share a common origin and many characteristics, but what distinguishes them from each other at the level of gene expression remains largely unknown. In this study, we compared the transcriptional profiles of freshly purified microglia, monocytes, and spleen macrophages using Affymetrix Mouse Genome arrays to identify genes predominantly expressed by microglia. Among tens of thousands of genes assayed, 127 potential candidates were found, including nine newly discovered genes encoding plasma membrane and extracellular proteins. In the brain, the latter were selectively expressed by microglia, as revealed by in situ hybridization. Three of them were confirmed to be exclusively (MSR2) or predominantly (GPR12, GPR34) expressed in the brain compared to the other tissues examined. Furthermore, all of these genes were upregulated in activated microglia after treatment with the demyelinating toxin cuprizone, suggesting that they play roles in neuroinflammation. In conclusion, this study reports the identification of new selective markers for microglia, which should prove useful not only to identify and isolate these cells, but also to better understand their distinctive properties. PMID- 17285590 TI - Cytoskeleton and paclitaxel sensitivity in breast cancer: the role of beta tubulins. AB - The antineoplastic effect of paclitaxel is mainly related to its ability to bind the beta subunit of tubulin, thus preventing tubulin chain depolarization and inducing apoptosis. The relevance of the Class I beta-tubulin characteristics have also been confirmed in the clinical setting where mutations of paclitaxel binding site of beta-tubulin Class I have been related to paclitaxel resistance in non small cell lung and ovarian cancers. In the present study, we verified the hypothesis of a relationship between molecular alterations of beta-tubulin Class I and paclitaxel sensitivity in a panel of breast cell lines with different drug IC(50). The Class I beta-tubulin gene cDNA has been sequenced detecting heterozygous missense mutations (exon 1 and 4) only in MCF-7 and SK-BR-3 lines. Furthermore, the expression (at both mRNA and protein level) of the different isotypes have been analyzed demonstrating an association between low cell sensitivity to paclitaxel and Class III beta-tubulin expression increasing. Antisense oligonucleotide (ODN) experiments confirmed that the inhibition of Class III beta-tubulin could at least partially increase paclitaxel chemosensitivity. The hypothesis of a relationship between beta-tubulin tumor expression and paclitaxel clinical response has been finally verified in a series of 92 advanced breast cancer patients treated with a first line paclitaxel-based chemotherapy. Thirty-five percent (95% CI: 45-31) of patients with high Class III beta-tubulin expression showed a disease progression vs. only 7% of patients with low expression (35% vs. 7%, p < 0.002). Our study suggests that Class III beta tubulin tumor expression could be considered a predictive biomarker of paclitaxel clinical resistance for breast cancer patients. PMID- 17285591 TI - Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan. AB - The Azoospermia Factor c (AZFc) region on the Y chromosome long arm is one of the least stable regions in the human genome. It consists almost entirely of very long repeats and is prone to rearrangement. Numerous structures at AZFc have been identified, and some of them have been reported to be associated with male infertility. We screened 580 Han Chinese in Taiwan for AZFc deletion and duplication using three PCR assays, and characterized the DAZ genes in selected subjects with additional Southern analyses. About 9.5% of our subjects have AZFc partial deletion, 2.8% have partial deletion followed by duplication, and 1.7% have partial duplication. The overall rearrangement frequencies vary significantly between different Y chromosome haplogroups (Yhgs), ranging from 2.9% in O3e to 100% in N and Q. All individuals in Yhg-N lack the sY1191 marker, but one out of three of them actually have four DAZ genes, indicating further duplication after the b2/b3 deletion. Our additional screening of 142 oligospermic men and 107 fertile controls found no significant difference in the frequencies of the gr/gr and the b2/b3 deletion. However, the frequency of AZFc partial duplication in the infertile group (7.0%) was significantly higher than that in the fertile control group (0.9%) and the general Taiwanese population (1.7%). Our results indicate that AZFc partial deletion and partial duplication are common polymorphisms in Han Chinese, and that the AZFc partial duplication, but not the AZFc partial deletion, is a risk factor for male infertility in the Taiwanese population. PMID- 17285592 TI - Secretagogin is a new neuroendocrine marker in the human prostate. AB - BACKGROUND: Neuroendocrine (NE) differentiation in prostate cancer (PCa), promoted by NE cell secreted products, appears to be associated with tumor progression, poor prognosis, and hormone-refractory disease. We recently reported secretagogin, a hexa-EF-hand Ca(2+) binding protein, as a novel NE marker in carcinoid tumors of the lung and the gastrointestinal tract. The present study analyzes the expression of secretagogin in normal and malign prostate tissue. METHODS: We analyzed immunoreactivity for secretagogin, chromogranin A (CgA), neuron specific enolase (NSE), and synaptophysin (SYN) in consecutive sections from 87 formalin-fixed paraffin-embedded (FFPE) benign hyperplastic (n = 10) and prostate adenocarcinoma (n = 77) specimens. The intracellular distribution of secretagogin, CgA, and NSE was examined by confocal fluorescent microscopy, and we characterized secretagogin in eight samples by Western blotting. RESULTS: Secretagogin is cytoplasmic and nuclear expressed in NE and NE differentiated cells, and to a lesser extent in epithelial cells, in the benign prostate and prostate adenocarcinoma cells. Secretagogin stained 82% (46/56) of benign and 71% (48/68) of prostate adenocarcinomas and co-localized with the NE markers CgA and NSE. The expression of secretagogin is significantly correlated to CgA (P < 0.001) and NSE (P < 0.048) in prostate adenocarcinoma and to CgA in normal epithelium (P < 0.028). CONCLUSIONS: Secretagogin is a novel NE marker in the prostate with more extended immunoreactivity compared to the NE markers CgA, SYN, and NSE. Secretagogin is widely expressed in prostatic adenocarcinoma as opposed to adenocarcinomas in other organs. PMID- 17285593 TI - Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe. AB - BACKGROUND: NOD1/CARD4 and NOD2/CARD15 are both intracellular pattern-recognition receptors. The NOD1/CARD4 gene lies within a previously described inflammatory bowel disease (IBD) locus (7p14). An association has been suggested between the NOD1/CARD4+32656 deletion*1 variant of a complex deletion*1/insertion*2 polymorphism and IBD in 1 recent study in Europe. Our aim was to assess the influence of NOD1/CARD4+32656 on disease susceptibility and phenotype in the Scottish and Swedish IBD populations. METHODS: A total of 3,962 individuals (1,791 IBD patients, 522 parents, 1,649 healthy controls) from 2 independent populations (Scotland and Sweden) were genotyped for NOD1/CARD4+32656 A/C by TaqMan and direct sequencing. Case-control, Transmission Disequilibrium Testing (TDT) and detailed genotype-phenotype (Montreal) analyses were performed. The case-control analysis had 80% power to detect an effect size of odds ratio (OR) 1.21 for IBD. RESULTS: In case-control analyses in Scottish and Swedish patients, none of the genotypes studied in IBD, Crohn's disease (CD) or ulcerative colitis (UC), differed significantly from controls (deletion*1 allelic frequency 73.9%, 73.6%, 73.9%, and 73.6%, respectively: all P > 0.8). No epistatic interaction with NOD2/CARD15 was seen for CD susceptibility. TDT analysis in our Scottish early onset cohort was negative. CONCLUSIONS: This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. A gene-wide haplotype-based approach may be preferable to analysis of individual variants to assess the contribution of the NOD1/CARD4 gene to IBD. PMID- 17285594 TI - Infliximab in Crohn's disease: TREAT your friend as if he might become an enemy? PMID- 17285595 TI - Exclusive increase of CX3CR1+CD28-CD4+ T cells in inflammatory bowel disease and their recruitment as intraepithelial lymphocytes. AB - BACKGROUND: CX3CL1/Fractalkine (FKN) has been reported to play important roles in various inflammatory diseases. We examined the role of FKN and its receptor CX3CR1 in T-cell migration in the inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD). METHODS: CX3CR1 expression on peripheral CD4(+) cells from normal controls (NL n = 24) and IBD patients (UC n = 28, CD n = 26) was examined using flow cytometry. CX3CR1(+)CD4(+) T cells were further characterized for surface antigens, cytokine production, and cytotoxic granule release by flow cytometry and ELISA. FKN expression in 53 colonic biopsy specimens (UC n = 20, CD n = 23, NL n = 10) was analyzed by quantitative PCR and immunohistochemistry. Isolated lamina propria and intraepithelial lymphocytes were also analyzed by flow cytometry (UC n = 10, CD n = 10, NL n = 6). RESULTS: CX3CR1(+)CD4(+) cells were increased in IBD while they were virtually absent in controls. Upregulation of CX3CR1 on CD4(+) T cells was positively correlated with disease activity. These unique T cells expressed markers for both effector memory and cytotoxic cells. Interestingly, CX3CR1 was expressed on CD4(+) T cells lacking CD28. CX3CR1(+)CD28(-)CD4(+) cells produced more IFN-gamma and TNF-alpha than CX3CR1(-) counterparts and released cytotoxic granules. FKN mRNA was upregulated in inflamed colonic tissues and robust expression of FKN was immunohistochemically observed on epithelial cells. Although CX3CR1(+) CD4(+) cells could not be detected in the gut, CD28(-)CD4(+) cells were found in IBD mainly as intraepithelial lymphocytes. CONCLUSIONS: FKN/CX3CR1 may contribute to the pathogenesis of IBD through the emergence of unique CX3CR1(+)CD28(-)CD4(+) T cells that can act both as proinflammatory and cytotoxic cells. PMID- 17285596 TI - Clinical significance of serum p53 antibodies in patients with ulcerative colitis and its carcinogenesis. AB - BACKGROUND: For early detection of ulcerative colitis (UC)-associated colorectal cancer (CRC), surveillance colonoscopy is recommended in UC patients at high risk. However, poor acceptability deteriorates its effectiveness and a suitable marker for selecting patients at high risk is needed. Here we evaluated clinical usefulness of the measurement of anti-p53 antibodies (Abs) by enzyme-linked immunosorbent assay (ELISA) using sera samples from UC patients. METHODS: Sera from 286 patients with UC, 82 patients with sporadic CRC, and 63 healthy controls (HC) were obtained. Serum anti-p53 antibodies were detected with ELISA. Immunohistochemical detection was also performed in patients who developed dysplasia or CRC. RESULTS: Serum p53 Ab was positive in 15.0% of UC, while it was positive only in 1.6% of HCs. In sporadic CRCs, 52.4% of 82 patients were positive. In UC patients with disease duration equal to or longer than 8 years, positivity of serum p53 Ab was significantly higher than those in patients with shorter duration. Eight of 13 (61.5%) UC patients with CRC or dysplasia were positive for serum p53 Abs, which was significantly higher than that in patients without neoplasia. All UC patients with CRC were positive for p53 staining, while 2 were negative for serum p53 Ab. Finally, levels of serum p53 Ab had fallen in 4 patients with CRC we could monitor after surgery. CONCLUSIONS: This study revealed that p53 Ab developed in the progression of UC-associated CRC but not in all patients with neoplasia, suggesting that serological detection of p53 Abs by ELISA is not suitable in primarily selecting patients at high risk; however, it is helpful in salvaging patients who drop from a surveillance program. PMID- 17285597 TI - Continuous locked suture technique for arterial anastomosis in rat small bowel transplantation. AB - Continuous locked suture technique in arterial anastomosis was used in a rat heterotopic small bowel transplantation model. Blood loss, time consumption and success rate of the technique, as well as long-term blood flow and histological changes of arterial anastomosis and intestinal graft were compared with the traditional simple continuous suture technique. The results showed that the time consumption was similar between the two techniques while the continuous locked suture technique had a higher success rate (P = 0.016) and was more secure than the simple continuous suture technique. Moreover, it provided a higher long-term blood flow. Under light microscopy and electron scanning microscopy, the anastomosis of continuous locked suture technique showed significantly less stenosis than those of simple continuous suture technique. No difference was found between the two techniques considering the graft intestinal histological changes. In conclusion, the continuous locked suture technique was a more superior technique than simple continuous suture technique in arterial end-to side anastomosis considering long-term hemodynamics. PMID- 17285598 TI - A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer. AB - BACKGROUND: Tumors with multidrug resistance (MDR) frequently up-regulate efflux proteins, including MDR-associated protein (MRP-1) and P-glycoprotein (Pgp). MDR represents an obstacle to successful chemotherapy treatment and is reversible in Pgp- or MRP-1-expressing cells by the inhibitor VX-710. A Phase II study was designed to evaluate VX-710 in combination with doxorubicin and vincristine in patients with sensitive, recurrent small cell lung cancer (SCLC). METHODS: Eligible patients had recurrent SCLC after a response to first-line chemotherapy. Stage 1 safety evaluation was completed with planned expansion if 9 responses were confirmed in the first 35 patients. Patients were treated every 21 days until progression or intolerable adverse events (AEs). RESULTS: Thirty-six patients were enrolled from 1998 to 2000. Neutropenia was the major toxicity, occurring in 26 of 36 patients (72%). Neutropenia was more severe (30% vs 20% grade 4) and developed earlier (58% vs 38% in Cycle 1) among the 15 patients who were enrolled prior to an amendment that required neutropenia prophylaxis. Four patients died on study: 2 from infections likely related to therapy and 2 from cancer progression. Seven of 36 patients (19%) had partial responses; 6 patients sustained responses through 6 cycles of treatment, with 1 response lasting 3 years. Three additional patients had unconfirmed responses, and 4 patients had stable disease. The median survival was 6 months. No correlative (99m)Tc sestamibi uptake in tumor tissue was observed with the addition of VX-710 in this study. CONCLUSIONS: The addition of VX-710 to doxorubicin and vincristine therapy did not significantly enhance antitumor activity or survival. Although there were durable responses, criteria were not met to proceed with Stage 2 expansion. PMID- 17285599 TI - Results of a multicenter phase II trial for older patients with c-Kit-positive acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) using low-dose Ara-C and Imatinib. AB - BACKGROUND: Imatinib (IM) is a potent tyrosine kinase inhibitor of c-Kit. c-Kit is expressed in the majority of patients with acute myeloid leukemia (AML). Whereas clinical trials evaluating monotherapy with IM in AML revealed low response rates, Ara-C and IM showed synergistic effects in vitro. This suggested evaluation of a combination treatment. METHODS: Low-dose Ara-C (LDAC) combined with IM was tested to determine the efficacy and safety of this regimen. Forty patients from 4 centers with c-Kit-positive AML (n = 34) and high-risk myelodysplastic syndrome (HR-MDS) (n = 6) with a median age of 73 years were enrolled. They were either not eligible for myelosuppressive therapy and/or had recurring/refractory disease. RESULTS: Thirty-eight patients were evaluable for analysis. In 6 of 38 patients a blast response was observed. Eight of 38 patients showed stable disease for more than 2 months. The objective hematologic response rate was low (11%), with 2 patients showing hematologic improvement and 1 each with a partial response (PR) or complete response (CR). Median overall survival was 138 days, with 20% of patients alive after an observation period of 600 days. Study medication was applied in an ambulatory setting with minimal hospitalization time, an early mortality rate of only 18.9%, and a low toxicity rate. CONCLUSIONS: LDAC plus IM does not appear to be inferior in older AML patients incomparison with historic controls receiving myelosuppressive therapy. However, this trial also shows that LDAC/IM does not appear to be more effective than LDAC monotherapy in a patient population not selected for appropriate molecular markers. PMID- 17285600 TI - Maternal and perinatal characteristics in relation to neuroblastoma. AB - BACKGROUND: Neuroblastoma is the most common malignancy among infants, but risk factors remain poorly understood. Because most patients present in the first few years of life, it has been hypothesized that prenatal and perinatal exposures may contribute to the pathogenesis of neuroblastoma. METHODS: A population-based case control study was conducted by using linked birth and cancer registry records from 1980 to 2004 in Washington State. Maternal and infant characteristics from birth and hospital discharge records for 240 cases of neuroblastoma and 2400 controls were compared. RESULTS: Neuroblastoma was associated with the presence of major congenital abnormalities (odds ratio [OR], 6.86; [95% CI], 2.92-16.08), particularly with cardiac abnormalities (OR, 5.84; 95% CI, 1.93-17.66), even after excluding abnormalities near the primary tumor. A borderline association was observed with maternal gestational diabetes (OR, 1.84; 95% CI, 0.98-3.47). The magnitude of both associations was greater when the analysis was limited to children who were diagnosed at age <1 year. CONCLUSIONS: The findings from this population-based study supported prior case-control studies that identified an etiologic link between neuroblastoma and congenital abnormalities. However, to the authors' knowledge, the association between neuroblastoma and maternal diabetes has not been reported previously and requires further study. PMID- 17285601 TI - Impact of the alcohol-dehydrogenase (ADH) 1C and ADH1B polymorphisms on drinking behavior in nonalcoholic Japanese. AB - A linkage disequilibrium (LD) between the alcohol-dehydrogenase 1B (ADH1B) and alcohol-dehydrogenase 1C (ADH1C) polymorphisms adds complexity to differentiating the significance of these two genetic polymorphisms on drinking behavior and alcoholism. We have recently shown the importance of the ADH1B polymorphism on habitual drinking in the Japanese population; however, the issue regarding the LD between the ADH1B and ADH1C polymorphisms remains to be clarified. Here, we conducted a cross-sectional study in 2,299 nonalcoholic Japanese individuals. Drinking behavior was examined with regard to haplotypes of the ADH1B and ADH1C polymorphisms. Strength of association was assessed by sex and aldehyde dehydrogenase 2 (ALDH2) adjusted odds ratios (OR) and their 95% confidence intervals (CIs) for the haplotype of the ADH1B and ADH1C polymorphisms. The ORs for habitual drinking were significant for ADH1B*2(rapid)-ADH1C*2(slow) (OR = 1.03; 95% CI: 1.01-1.05), ADH1B*1(slow)-ADH1C*1(rapid) (OR = 1.15; 95% CI: 1.14 1.16), and ADH1B*1(slow)-ADH1C*2(slow) (OR = 1.31; 95% CI: 1.29-1.32) compared with ADH1B*2(rapid)-ADH1C*1(rapid). This trend was evident among males. Similarly, a significantly increased risk of heavy drinking was observed for each haplotype compared with ADH1B*2(rapid)-ADH1C*1(rapid). In conclusion, this study showed a significant impact of the ADH1C polymorphism on habitual drinking, regardless of the ADH1B/ALDH2 polymorphisms. PMID- 17285602 TI - Recent improvement in the survival of patients with advanced nonsmall cell lung cancer enrolled in phase III trials of first-line, systemic chemotherapy. AB - BACKGROUND: Few studies have assessed formally whether treatment outcomes have improved substantially over the years for patients with advanced nonsmall cell lung cancer (NSCLC) enrolled in Phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials. METHODS: The literature was searched to identify trials that addressed the role of chemotherapy regimens in the first-line setting for the treatment of advanced NSCLC. Trends were tested by using multiple regression analysis. RESULTS: In total, 121 Phase III trials were identified that involved 42,768 patients with 263 chemotherapy arms and 11 best supportive care (BSC) arms, all of which were initiated between 1982 and 2002. Although the number of randomized patients and the proportion of patients with metastatic disease had increased over the years, the number of patients with a poor performance status who were accrued into the trials had decreased. Cisplatin-based chemotherapy was been investigated most frequently during the period. The multiple regression analysis revealed a significant improvement in median survival and in the median time to disease progression over the years, with annual prolongations of 0.1203 months (3.609 days) and 0.0617 months (1.851 days), respectively (P< .0001 and P < .0130, respectively). In addition, the use of cisplatin and carboplatin was associated significantly with survival prolongation. The median survival for patients who received BSC also increased progressively over the years (P = .0487). CONCLUSIONS: The survival of patients with NSCLC in Phase III trials improved slowly but steadily over time, although the main factors responsible for this improvement remain unknown. Nonetheless, the current results also suggested that novel targets and new agents will be required in the future fight against advanced NSCLC. PMID- 17285603 TI - Genetic variants in MGMT and risk of lung cancer in Southeastern Chinese: a haplotype-based analysis. AB - O6-alkylguanine-DNA alkyltransferase (MGMT) is a universal DNA repair protein involved in the DNA direct reversal repair pathway that copes with alkylating carcinogens. Reduced MGMT expression as well as enzyme activity may result in an increased susceptibility to cancers. To elucidate the role of sequence variation in MGMT in the etiology of lung cancer, we conducted a comprehensive association study focusing on linkage disequilibrium (LD) structure of common variations across the MGMT sequence and its modification effect on smoking-related lung cancer risk. We rebuilt the LD block of MGMT by genotyping 39 SNPs and selected a subset of 10 haplotype-tagging SNPs (htSNP) and three pre- and interblock SNPs to capture variation across MGMT. By using a haplotype-based multifactor dimensionality reduction (MDR) analysis, we found that there were significant more-than-multiplicative interactions between diplotypes in block 5 and cumulative smoking and additive interaction between genotypes of preblock SNP rs1625649:C>A and smoking status in relation on lung cancer risk. Diplotypes in block 3 and block 5, genotypes of rs1625649:C>A, and trichotomized cumulative smoking are the four factors included in the MDR-defined best model on lung cancer risk. When these variables were combined and dichotomized, we found that subjects carrying the combined risk stratum had a significantly increased risk for lung cancer of 4.10-fold (odds ratio [OR]=4.10, 95% confidence interval [CI]=3.12-5.37, P=2.09 x 10(-24)). These findings suggest that genetic variants in MGMT may modulate the risk of smoking-related lung cancer. This haplotype based interaction analysis might provide a "proof-of-principle" approach for studying candidate genes in cancer susceptibility. PMID- 17285604 TI - Investigation of 3,4-methylenedioxybenzene methoxyl methacrylate as coinitiator and comonomer for dental application. AB - In this study, 3,4-methylenedioxybenzene methoxyl methacrylate (MDBMM) was synthesized for the purpose of replacing both triethylene glycol dimethacrylate (TEGDMA) and tertiary amine, which was usually used as a comonomer and coinitiator for dental resin, respectively. Urethane dimethacrylate (UDMA) was chosen as a monomer. Real time near Fourier transform infrared (FTIR) with a horizontal sample holder and dynamic mechanical analyzer (DMA) were used to study the kinetics and mechanical properties, respectively. The results showed that the addition of MDBMM as a coinitiator in UDMA/TEGDMA/CQ (70/30/0.5 wt %) system led to the increase of the rate of polymerization. When compared with the commercial polymerizable amine, 2-(N,N-dimethyl amino)ethyl methacrylate (DMEM), MDBMM showed comparable initiating reactivity and led to higher modulus around human body temperature (37 degrees C). MDBMM as a comonomer resulted in slightly higher final double bond conversion than that of TEGDMA, which brought higher modulus around 37 degrees C. Therefore, MDBMM can be used as both potential coinitiator and comonomer for dental application. PMID- 17285606 TI - Water sorption and solubility of contemporary resin-based filling materials. AB - PURPOSE: Evaluation of water sorption and solubility of contemporary resin-based filling materials. METHODS: Specimens of Herculite (HE), Point 4 (P4), TetricCeram (TC), Miris (MI), TetricCeram HB (HB), Solitaire 2 (SO), SureFil (SU), Definite (DE), Admira (AD), Dyract AP (DY), Compoglass F (CO), and TetricFlow (TF) were prepared according to ISO 4049. Water sorption and solubility were measured after water storage at 37 degrees C for 7 days. RESULTS: Water sorption was HE 14 microg mm(-3), P4 17 microg mm(-3), TC 12 microg mm(-3), MI 13 microg mm(-3), HB 9 microg mm(-3), SO 18 microg mm(-3), SU 9 microg mm(-3), DE 14 microg mm(-3), AD 27 microg mm(-3), DY 19 microg mm(-3), CO 23 microg mm( 3), and TF 19 microg mm(-3). Solubility was HE 3 microg mm(-3), P4 3 microg mm( 3), TC 1 microg mm(-3), MI 0 microg mm(-3), HB 0 microg mm(-3), SO 3 microg mm( 3), SU 0 microg mm(-3), DE 1 microg mm(-3), AD 2 microg mm(-3), DY 4 microg mm( 3), CO -2 microg mm(-3), and TF 1 microg mm(-3). CONCLUSION: All materials met the corresponding requirement in ISO 4049. Filler load negatively correlated with water sorption but not with solubility. There was an influence of the resin matrix, too. No significant differences were found between composites, ormocers, and compomers. PMID- 17285605 TI - Cardiovascular changes after pulmonary embolism from injecting calcium phosphate cement. AB - Concerns have been raised that the use of calcium phosphate (CaP) cements for the augmentation of fractured, osteoporotic bones may aggravate cardiovascular deterioration in the event of pulmonary cement embolism by stimulating coagulation. The aim of the present study was therefore to investigate the cardiovascular changes after pulmonary embolism of CaP cement using an animal model. In 14 sheep, 2.0 mL CaP or polymethylmethacrylate cement were injected intravenously. Cardiovascular parameters and antithrombin levels were monitored until 60 min postinjection. Postmortem, lungs were subjected to CT scanning, and 3D reconstruction of the cement was performed. Intravenous injection of CaP cement resulted in a more severe increase in pulmonary arterial pressure and decrease in arterial blood pressure. Disintegration of the CaP cement seemed to be the reason for the more severe reaction. There was no evidence of thromboembolism. Disintegration of CaP cement in circulating blood does not only compromise the mechanical properties, but also represents a risk of cardiovascular complications. Reliable cohesion of CaP cements in an aqueous environment is essential for clinical applications such as osteoporotic bone augmentation. PMID- 17285607 TI - Carvable calcium phosphate bone substitute material. AB - This study investigated the use of partially set hydroxyapatite forming calcium phosphate cement as a carvable and mechanically stable bone substitute material. Hydroxyapatite-forming cements were made of either mechanically activated alpha tricalcium phosphate or a mixture of tetracalcium phosphate and dicalcium phosphate anhydrous and setting was arrested up to 4 h post setting. The study showed that these partially set rigid samples of defined geometry could be carved into a desired shape when the degree of reaction was 30-40% and the relative porosity between 40 and 50%; samples are then expected to set completely after implantation in the presence of water or serum, having the same compressive strength as a continuously set calcium phosphate cement (up to 36 MPa). The development of compressive strength, phase composition, and crystallinity when varying production parameters of these partially "preset" bone substitute materials are presented for both cement systems. PMID- 17285608 TI - Materials characterization of explanted polypropylene hernia meshes. AB - Hernia repair with prosthetic mesh significantly decreases the rate of recurrence compared with traditional, primary suture repair by reducing the tension on the edges of the wound. However, there are several complications associated with the use of mesh that may be due to the chronic inflammatory reaction to the mesh or a loss of compliance after degradation of the material. Mesh contraction and migration can also occur, sometimes resulting in a recurrent hernia. Based on the chemical structure of the polypropylene mesh material and the physiological conditions to which it is subjected, it is possible that oxidation is responsible for these changes in material properties. Oxidation would result in surface cracking, decreased melting temperature, loss of mass, and reduced compliance of the material. The objective of this study was to identify physiochemical changes in the surface and bulk properties of explanted polypropylene hernia meshes compared to pristine polypropylene mesh materials. Several characterization techniques were utilized, including scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and compliance testing. Overall, the results supported our hypothesis that oxidation is involved with the degradation of polypropylene hernia mesh materials. PMID- 17285609 TI - Biomedical applications of diamond-like carbon coatings: a review. AB - Owing to its superior tribological and mechanical properties with corrosion resistance, biocompatibility, and hemocompatibility, diamond-like carbon (DLC) has emerged as a promising material for biomedical applications. DLC films with various atomic bond structures and compositions are finding places in orthopedic, cardiovascular, and dental applications. Cells grew on to DLC coating without any cytotoxity and inflammation. DLC coatings in orthopedic applications reduced wear, corrosion, and debris formation. DLC coating also reduced thrombogenicity by minimizing the platelet adhesion and activation. However, some contradictory results (Airoldi et al., Am J Cardiol 2004;93:474-477, Taeger et al., Mat-wiss u Werkstofftech 2003;34:1094-1100) were also reported that no significant improvement was observed in the performance of DLC-coated stainless stent or DLC coated femoral head. This controversy should be discussed based on the detailed information of the coating such as atomic bond structure, composition, and/or electronic structure. In addition, instability of the DLC coating caused by its high level of residual stress and poor adhesion in aqueous environment should be carefully considered. Further in vitro and in vivo studies are thus required to confirm its use for medical devices. PMID- 17285610 TI - Inhibitory effects of root canal sealers on the expression of inducible nitric oxide synthase in lipopolysaccharide-stimulated murine macrophage cells. AB - Excessive production of nitric oxide (NO) is associated with inflammation. In the present study, we examined the effects of root canal sealers (N2 Universal, Sealapex, and AH26) on NO production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Root canal sealers decreased NO synthesis in LPS-induced RAW 264.7 macrophages in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated markedly lower levels of iNOS mRNA and protein in LPS-activated macrophage cells treated with root canal sealers compared with untreated cells. From these results, we conclude that root canal sealers do not inhibit NO synthesis by direct inhibition of the enzyme, but rather through inhibition of iNOS mRNA expression (leading to a decrease in iNOS protein expression). Our data, therefore, suggest that root canal sealers may be an effective inhibitor of LPS-induced inflammatory effects in macrophage cells. Further in vitro and in vivo studies are necessary to confirm the effects of root canal sealers on the inflammatory processes. PMID- 17285611 TI - Antibacterial activity of silver-doped silica glass microspheres prepared by a sol-gel method. AB - Various kinds of inorganic substances doped with silver ions have been developed as antibacterial materials, and some have already been commercialized. Previously, we successfully prepared colorless silica glass microspheres doped with silver ions in combination with aluminum ions by a sol-gel method. However, the antibacterial activity of the microspheres was not maintained for long periods in an aqueous environment, since the silver ions were located only in a thin layer near the surface of the microspheres. In this study, silica glass microspheres in which silver ions are uniformly distributed were attempted to be prepared. A tetraethoxysilane ethanol solution was mixed with aqueous silver nitrate and aluminum nitrate solutions to be subjected to almost simultaneous hydrolysis and polycondensation. An ammonia solution was then added, to form microspheres. Monodispersed microspheres about 0.1 microm in diameter were obtained, which did not show coloring even after heat treatment at 600-1000 degrees C, indicating that the silver in the microspheres took the form of Ag(+) ions and not colloid, even after the heat treatments. Microspheres heat-treated at temperatures ranging from 700 to 800 degrees C showed much higher antibacterial activity than commercial antibacterial zeolites and maintained their high antibacterial activities for long periods in an aqueous environment. Polypropylene plates and films mixed with the microspheres heat-treated at 800 degrees C showed excellent antibacterial properties. PMID- 17285612 TI - Selection of the sacral nerve posterior roots to establish skin-CNS-bladder reflex pathway: an experimental study in rats. AB - The purpose of this study was to explore the innervations of different sacral nerve posterior roots to bladder, and to provide evidence for further study of skin-CNS-bladder reflex pathway in the spinal cord injury patient. Spinal cord injury was produced in 10 rats. The bilateral spinal posterior roots of S1-S4 were electrically stimulated, and the bladder plexus action, bladder smooth muscle complex action potential, and intravesical pressure were examined and measured. The results showed that all the sacral nerve posterior roots were involved in innervations of bladder in rats. Among them, the S2 sacral nerve is the dominant nerve in innervations of bladder, followed by S1, S3, and S4 sacral nerve posterior roots. This study has provided valuable information for selection of sacral nerve posterior root for further study of the artificial bladder reflex arc for improving the micturition function in spinal cord injury patients. PMID- 17285613 TI - Cytokine secretion from monocytes persists differentially after activator removal One mechanism of long-term biological response to implants. AB - Biomedical implants significantly improve the quality of life in an ever increasing number of patients. However, inflammation of tissues around implants remains a long-term, post-placement sequelae that may contribute to implant failure. Infection-mediated failure is partly a consequence of inappropriate host response and chronic inflammation, and is mediated primarily by the secretory products of monocytes and macrophages. Although the secretion of inflammatory mediators from activated monocytes is well characterized, the resolution of mediator levels post-activation is relatively unstudied. The current study defines the time course of cytokine secretion by activated human monocytes after the activator has been removed. THP1 human monocytes were activated by LPS, and cytokine secretion was monitored over time after LPS removal using enzyme-linked immunosorbent assays (TNFalpha or IL8) or a cytokine array. The release of cytokines was compared with conditions without LPS removal. As expected, secretion of nearly all cytokines was reduced when LPS was removed, but the amount of the reduction was highly cytokine-dependent. Furthermore, levels of cytokines were stable in medium alone but not in cell-culture, suggesting an active process to either degrade or internalize secreted cytokines. Our results are consistent with clinical experience that inflammation resolves rapidly after treatment to remove bacteria or inflamed tissue. However, the differential cytokine regulation indicates a sophisticated coordination of cytokine levels probably associated with management of the wound healing response after removal of the bacterial insult. This wound healing response is one critical component of the long-term success of biomedical implants. PMID- 17285614 TI - Predisposing factors of restless legs syndrome in pregnancy. AB - The occurrence of restless legs syndrome in pregnancy is well known. However, the mechanism of this association is unclear. In this study, we aimed to identify the factors that predispose women to have restless legs syndrome during pregnancy. A total of 146 pregnant women were included in the study. Patients were asked questions regarding demographic characteristics, complications of pregnancy, medical therapy (vitamin and iron intake), sleep disorders, muscle cramps, and excessive daytime sleepiness. Electroneurography, routine blood biochemistry tests, complete blood count, and thyroid function tests were performed and vitamin B12, folic acid, serum iron, iron-binding capacity, ferritin, iron saturation, prolactin, estradiol, and progesterone were measured. Of the participants, 38 were diagnosed as having restless legs syndrome. In women with restless legs syndrome, additional medical problems, night cramps, and excessive daytime sleepiness were more frequent. In women without restless legs syndrome, serum hemoglobin levels were significantly higher and the use of supplemental iron or vitamins was greater. Among the women with restless legs syndrome, progesterone levels were slightly higher but this difference was not statistically significant. In summary, in this study, lower hemoglobin levels and supplementation deficits of iron and vitamins were found be the risk factors for restless legs syndrome in pregnancy. PMID- 17285615 TI - Therapeutic plasmapheresis as a bridge to liver transplantation in fulminant Wilson disease. AB - Wilson disease is an autosomal recessive disorder of copper metabolism that leads to the accumulation of copper mainly in the liver, cornea, brain, and kidney. Rarely, Wilson disease can present as fulminant hepatic failure with direct antiglobulin test-negative hemolytic anemia and renal failure. In the absence of liver transplantation, this disease is uniformly fatal because medical therapy is ineffective. This report describes the successful use of plasmapheresis for a patient with fulminant Wilson disease as a bridge to transplantation. Five daily therapeutic plasmapheresis procedures using fresh frozen plasma as a replacement fluid were performed over 6 days. Serum copper, urinary copper excretion, and hemolysis were significantly reduced and renal function improved. The patient's clinical status improved and she remained clinically stable until a liver transplant was possible. Plasmapheresis can be a successful medical treatment in fulminant Wilson disease and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible. PMID- 17285617 TI - Do infections provoke exacerbations and relapses of thrombotic thrombocytopenic purpura? AB - Several case reports have suggested an association between infections and thrombotic thrombocytopenic purpura (TTP). In Case 1, a 37-year-old female presented with TTP 6 times over 7 years, requiring 242 therapeutic plasma exchanges (TPE), for a per-course range of 4-57 TPE (median 48), and treatment durations of 4-241 days (median 71 days), largely on account of multiple exacerbations (range 0-3, median 3). Twelve of 17 (71%) of her presentations or exacerbations were associated with suspected infections, with confirmation in 9 episodes. These included pulmonary TB, CMV pneumonitis, mucocutaneous HSV, ventilator-associated or urinary tract-associated gram-negative sepsis, central line-associated staphylococcal bacteremia, and cellulitis. Except for TB, all infections occurred after splenectomy, which had been performed on day 33 of presentation 1. In Case 2, a 24-year-old female presented with TTP 3 times over 15 months. Her courses were managed with brief courses of TPE (5-11 treatments per course, median 5). Suppressed ADAMTS13 levels due to inhibitors were confirmed twice. Presentation 1 was antedated by atypical community acquired pneumonia. Presentation 3 (and possibly 2) followed prolonged, progressive, antibiotic-refractory periodontal infections ultimately requiring exodontic surgery. Our cases add to a literature that suggests that infection may be associated with exacerbations or relapses of TTP in some patients. Our patients demonstrated repeated TTP exacerbations in association with different infectious agents. A better understanding of the possible relationship between infection and clinical expression of TTP might lead to improved treatment decisions for patients with this complex illness. PMID- 17285616 TI - Drug-resistant bullous pemphigoid and inflammatory bowel disease in a pediatric case successfully treated by plasma exchange and extracorporeal photochemotherapy. AB - Bullous pemphigoid (BP) is an autoimmune skin disease that occurs mainly in elderly patients; onset of BP is rare in childhood. Inflammatory bowel diseases (IBD), by contrast, have a pediatric onset in 25% of presenting cases, requiring expert multidisciplinary management. Here we report a pediatric case of IBD (involving stomach, duodenum, ileum, and colon-rectum) associated with a disseminated form of drug-resistant BP successfully treated by plasma exchange (PEX), extracorporeal photochemotherapy (ECP), and corticosteroid therapy. The addition of PEX and ECP to standard treatment induced no severe side effects, prompted a rapidly achieved complete and long-term remission, and allowed dose tapering of the immunosuppressive drugs over an 18-month follow-up. PMID- 17285618 TI - Successful repeat therapy with rituximab for relapsed thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that is treated successfully with therapeutic plasma exchange (TPE) and often with corticosteroids; however, almost one third of TTP patients have treatment failures that require either long-term TPEs or other adjunct therapies. Recent insights into the autoimmune-pathophysiology of this disease provide the rationale for immune-based therapies. Cumulative evidence suggests that rituximab, an anti-CD20 antibody that depletes B-cells temporarily, is an effective therapy in patients with refractory or relapsing TTP. We report here two patients with chronic relapsing TTP who were treated successfully with rituximab. However, both experienced TTP relapse following sustained and prolonged remissions for 21 and 37 months, respectively. They responded favorably with repeat therapy with rituximab. The benefits of rituximab treatment for refractory or relapsing TTP as well as in the prevention of recurrences are discussed. PMID- 17285619 TI - Heparin-induced thrombocytopenia: an autoimmune disorder regulated through dynamic autoantigen assembly/disassembly. AB - Heparin-induced thrombocytopenia (HIT) is the most common drug-induced, antibody mediated cause of thrombocytopenia and thrombosis. HIT is caused by IgG antibodies that bind to epitopes on platelet factor 4 (PF4) released from activated platelets that develop when it forms complexes with heparin. Anti PF4/antibodies develop in over 50% of patients undergoing surgery involving cardiopulmonary bypass (CPB), an incidence 20-fold higher than HIT. Why might this occur? Binding of HIT IgG occurs only over a narrow molar ratio of reactants, being optimal at 1 mol PF4 tetramer to 1 mol unfractionated heparin (UFH). At these ratios, PF4 and UFH form ultralarge (>670 kD) complexes that bind multiple IgG molecules/complex, are highly antigenic, and promote platelet activation. Low molecular weight heparin (LMWH), which is less antigenic, forms ultralarge complexes less efficiently and largely at supratherapeutic concentrations. In transgenic mice that vary in expression of human PF4 on their platelets, antigenic complexes form between PF4 and endogenous chondroitin sulfate. Binding of HIT IgG to platelets and induction of thrombocytopenia in vivo is proportional to PF4 expression. Heparin prolongs the duration and exacerbates the severity of the thrombocytopenia. High doses of heparin, as used in CPB, or protamine, which competes with PF4 for heparin, disrupts antigen formation and prevents thrombocytopenia induced by HIT antibody. These studies may help explain the disparity between the incidence of antibody formation and clinical disease and may help identify patients at risk for HIT (high platelet PF4). They also demonstrate that this autoimmune disease can be modulated at the level of autoantigen formation and point to rational means to intervene proximal to thrombin generation. PMID- 17285621 TI - Effects of single SNPs, haplotypes, and whole-genome LD maps on accuracy of association mapping. AB - We describe an association mapping approach that utilizes linkage disequilibrium (LD) maps in LD units (LDU). This method uses composite likelihood to combine information from all single marker tests, and applies a model with a parameter for the location of the causal polymorphism. Previous analyses of the poor drug metabolizer phenotype provided evidence of the substantial utility of LDU maps for disease gene association mapping. Using LDU locations for the 27 single nucleotide polymorphisms (SNPs) flanking the CYP2D6 gene on chromosome 22, the most common functional polymorphism within the gene was located at 15 kb from its true location. Here, we examine the performance of this mapping approach by exploiting the high-density LDU map constructed from the HapMap data. Expressing the locations of the 27 SNPs in LDU from the HapMap LDU map, analysis yielded an estimated location that is only 0.3 kb away from the CYP2D6 gene. This supports the use of the high marker density HapMap-derived LDU map for association mapping even though it is derived from a much smaller number of individuals compared to the CYP2D6 sample. We also examine the performance of 2-SNP haplotypes. Using the same modelling procedures and composite likelihood as for single SNPs, the haplotype data provided much poorer localization compared to single SNP analysis. Haplotypes generate more autocorrelation through multiple inclusions of the same SNPs, which could inflate significance in association studies. The results of the present study demonstrate the great potential of the genome HapMap LDU maps for high-resolution mapping of complex phenotypes. PMID- 17285622 TI - Statistical methods for haplotype-based matched case-control association studies. AB - Kraft et al. [2005] proposed a method for matched haplotype-based association studies and compared the performances of six analytic strategies for estimating the odds ratio parameters using a conditional likelihood function. Zhang et al. [2006] modified the conditional likelihood and proposed a new method for matched haplotype-based association studies. The main assumptions of Zhang et al. were that the disease was rare, the population was in Hardy-Weinberg equilibrium (HWE), and the haplotypes were independent of the covariates and matching variable(s). In this article, we modify the estimation procedure proposed by Zhang et al. and introduce a fixation index so that the assumption of HWE is relaxed. Using the Wald test, we compare the current modified method with the procedure developed by Kraft et al. through simulations. The results show that the modified method is uniformly more powerful than that described in Kraft et al. Furthermore, the results indicate that the modified method is quite robust to the rare disease assumption. PMID- 17285620 TI - The polypeptide composition of moving and stationary neurofilaments in cultured sympathetic neurons. AB - Studies on the axonal transport of neurofilament proteins in cultured neurons have shown they move at fast rates, but their overall rate of movement is slow because they spend most of their time not moving. Using correlative light and electron microscopy, we have shown that these proteins move in the form of assembled neurofilament polymers. However, the polypeptide composition of these moving polymers is not known. To address this, we visualized neurofilaments in cultured neonatal mouse sympathetic neurons using GFP-tagged neurofilament protein M and performed time-lapse fluorescence microscopy of naturally occurring gaps in the axonal neurofilament array. When neurofilaments entered the gaps, we stopped them in their tracks using a rapid perfusion and permeabilization technique and then processed them for immunofluorescence microscopy. To compare moving neurofilaments to the total neurofilament population, most of which are stationary at any point in time, we also performed immunofluorescence microscopy on neurofilaments in detergent-splayed axonal cytoskeletons. All neurofilaments, both moving and stationary, contained NFL, NFM, peripherin and alpha-internexin along>85% of their length. NFH was absent due to low expression levels in these neonatal neurons. These data indicate that peripherin and alpha-internexin are integral and abundant components of neurofilament polymers in these neurons and that both moving and stationary neurofilaments in these neurons are complex heteropolymers of at least four different neuronal intermediate filament proteins. PMID- 17285623 TI - Predicting disulfide connectivity patterns. AB - Disulfide bonds play an important role in stabilizing protein structure and regulating protein function. Therefore, the ability to infer disulfide connectivity from protein sequences will be valuable in structural modeling and functional analysis. However, to predict disulfide connectivity directly from sequences presents a challenge to computational biologists due to the nonlocal nature of disulfide bonds, i.e., the close spatial proximity of the cysteine pair that forms the disulfide bond does not necessarily imply the short sequence separation of the cysteine residues. Recently, Chen and Hwang (Proteins 2005;61:507-512) treated this problem as a multiple class classification by defining each distinct disulfide pattern as a class. They used multiple support vector machines based on a variety of sequence features to predict the disulfide patterns. Their results compare favorably with those in the literature for a benchmark dataset sharing less than 30% sequence identity. However, since the number of disulfide patterns grows rapidly when the number of disulfide bonds increases, their method performs unsatisfactorily for the cases of large number of disulfide bonds. In this work, we propose a novel method to represent disulfide connectivity in terms of cysteine pairs, instead of disulfide patterns. Since the number of bonding states of the cysteine pairs is independent of that of disulfide bonds, the problem of class explosion is avoided. The bonding states of the cysteine pairs are predicted using the support vector machines together with the genetic algorithm optimization for feature selection. The complete disulfide patterns are then determined from the connectivity matrices that are constructed from the predicted bonding states of the cysteine pairs. Our approach outperforms the current approaches in the literature. PMID- 17285624 TI - The Caribbean: riding the dark horse of HIV/AIDS towards a brighter future. PMID- 17285626 TI - Abstracts of the 6th Euroconference on Clinical Cell Analysis, September 14-16, 2006, Stresa, Italy. PMID- 17285625 TI - ZAP70 editorial: a follow-up to the special issue. PMID- 17285627 TI - Understanding the folding and stability of a zinc finger-based full sequence design protein with replica exchange molecular dynamics simulations. AB - Full sequence design protein FSD-1 is a designed protein based on the motif of zinc finger protein. In this work, its folding mechanism and thermal stability are investigated using the replica exchange molecular dynamics model with the water molecules being treated explicitly. The results show that the folding of the FSD-1 is initiated by the hydrophobic collapse, which is accompanied with the formation of the C-terminal alpha-helix. Then the folding proceeds with the formation of the beta-hairpin and the further package of the hydrophobic core. Compared with the beta-hairpin, the alpha-helix has much higher stability. It is also found that the N-capping motif adopted by the FSD-1 contributes to the stability of the alpha-helix dramatically. The hydrophobic contacts made by the side chain of Tyr3 in the native state are essential for the stabilization of the beta-hairpin. It is also found that the folding of the N-terminal beta-hairpin and the C-terminal alpha-helix exhibits weak cooperativity, which is consistent with the experimental data. Meanwhile, the folding pathway is compared between the FSD-1 and the target zinc finger peptide, and the possible role of the zinc ion on the folding pathway of zinc finger is proposed. Proteins 2007. (c) 2007 Wiley-Liss, Inc. PMID- 17285628 TI - An image analysis approach for automatic malignancy determination of prostate pathological images. AB - BACKGROUND: Determining malignancy of prostate pathological samples is important for treatment planning of prostate cancer. Traditionally, this is performed by expert pathologists who evaluate the structure of prostate glands in the biopsy samples. However, this is a subjective task due to inter- and intra-observer differences among pathologists. Also, it is time-consuming and difficult to some extent. Therefore, automatic determination of malignancy of prostate pathological samples is of interest. METHODS: A texture-based technique is first used to segment the prostate glands in the image. Features related to size and shape of these glands are then extracted and combined to generate an index, which is proportional to malignancy of cancer. A linear classifier is employed to classify the specimens into benign (low potential for malignancy) and malignant. RESULTS: The leave-one-out technique is employed to evaluate the method using two datasets. The first has 91 images with similar magnifications and illuminations while the second has 199 images with different magnifications and illuminations. In the experiments, accuracies of about 98 and 95% have been achieved for these two datasets, respectively. CONCLUSIONS: An image analysis approach is employed to evaluate prostate pathological images. Experimental results show that the proposed method can successfully classify the prostate biopsy samples into benign and malignant. They also show that the proposed method is robust to variations in magnification and illumination. PMID- 17285629 TI - Diagnosing PNH with FLAER and multiparameter flow cytometry. AB - BACKGROUND: PNH is an acquired hematopoietic stem cell disorder leading to a partial or absolute deficiency of all glycophosphatidyl-inositol (GPI)-linked proteins. The classical approach to diagnosis of PNH by cytometry involves the loss of at least two GPI-linked antigens on RBCs and neutrophils. While flow assays are more sensitive and specific than complement-mediated lysis or the Hams test, they suffer from several drawbacks. Bacterial aerolysin binds to the GPI moiety of cell surface GPI-linked molecules and causes lysis of normal but not GPI-deficient PNH cells. FLAER is an Alexa488-labeled inactive variant of aerolysin that does not cause lysis of cells. Our goals were to develop a FLAER based assay to diagnose and monitor patients with PNH and to improve detection of minor populations of PNH clones in other hematologic disorders. METHODS: In a single tube assay, we combined FLAER with CD45, CD33, and CD14 allowing the simultaneous analysis of FLAER and the GPI-linked CD14 structure on neutrophil and monocyte lineages. RESULTS: Comparison to standard CD55 and CD59 analysis showed excellent agreement. Because of the higher signal to noise ratio, the method shows increased sensitivity in our hands over single (CD55 or CD59) parameter analysis. Using this assay, we were able to detect as few as 1% PNH monocytes and neutrophils in aplastic anemia, that were otherwise undetectable using CD55 and CD59 on RBC's. We also observed abnormal FLAER staining of blast populations in acute leukemia. In these cases, the neutrophils stained normally with FLAER, while the gated CD33bright cells failed to express normal levels of CD14 and additionally showed aberrant CD45 staining and bound lower levels of FLAER. CONCLUSION: FLAER combined with multiparameter flow cytometry offers an improved assay for diagnosis and monitoring of PNH clones and may have utility in detection of unsuspected myeloproliferative disorders. PMID- 17285630 TI - Calcium-sensing receptor stimulates secretion of an interferon-gamma-induced monokine (CXCL10) and monocyte chemoattractant protein-3 in immortalized GnRH neurons. AB - Biology of GnRH neurons is critically dependent on extracellular Ca(2+) (Ca(2+) (o)). We evaluated differences in gene expression patterns with low and high Ca(2+) (o) in an immortalized GnRH neuron line, GT1-7 cells. Mouse global oligonucleotide microarray was used to evaluate transcriptional differences among the genes regulated by elevated Ca(2+) (o). Our result identified two interferon gamma (IFNgamma)-inducible chemokines, CXCL9 and CXCL10, and a beta chemokine, monocyte chemoattractant protein-3 (MCP-3/CCL7), being up-regulated in GT1-7 cells treated with high Ca(2+) (o) (3.0 mM) compared with low Ca(2+) (o) (0.5 mM). Up-regulation of these mRNAs by elevated Ca(2+) (o) was confirmed by quantitative PCR. Elevated Ca(2+) (o) stimulated secretion of CXCL10 and MCP-3 but not CXCL9 in GT1-7 cells, and this effect was mediated by an extracellular calcium-sensing receptor (CaR) as the dominant negative CaR attenuated secretion of CXCL10 and MCP-3. CXCL10 and MCP-3 were localized in mouse GnRH neurons in the preoptic hypothalamus. Suppression of K(+) channels (BK channels) with 25 nM charybdotoxin inhibited high-Ca(2+) (o)-stimulated CXCL10 release. Accordingly, CaR activation by a specific CaR agonist, NPS-467, resulted in the activation of a Ca(2+)-activated K(+) channel in these cells. CaR-mediated MCP-3 secretion involves the PI3 kinase pathway in GT1-7 cells. MCP-3 stimulated chemotaxis of astrocytes treated with transforming growth factor-beta (TGFbeta). With TGFbeta treated astrocytes, we next observed that conditioned medium from GT1-7 cells treated with high Ca(2+) promoted chemotaxis of astrocytes, and this effect was attenuated by a neutralizing antibody to MCP-3. These results implicate CaR as an important regulator of GnRH neuron function in vivo by stimulating secretion of heretofore unsuspected cytokines, i.e., CXCL10 and MCP-3. PMID- 17285631 TI - Dynamical behavior of the vascular endothelial growth factor: biological implications. AB - The vascular endothelial growth factor (VEGF) seems to be the most important regulator of physiological and pathological angiogenesis, being, for this reason, a favorite target for therapies against angiogenesis-related diseases. VEGF is a homodimer in which the monomers are formed by beta-strands interconnected on the poles by three loops. A recent work showed that an intimate relationship between loops-1 and -3 is required for high affinity binding to the receptors (Kiba et al., J Biol Chem 2003;278:13453-13461). In this work, we report the results of a 10-ns molecular dynamics simulation of VEGF. We analyzed the dynamical behavior of the protein (using a dynamical cross-correlation map) and found that it is governed by a high degree of correlation between the motions of the loops. We also performed a principal component analysis and found an overall motion in which the opposite poles are projected against each other, just like the movement of the wings of a butterfly. From the biological point of view, it is likely that this motion would facilitate receptor binding since VEGF must enter a restricted cavity formed by the two subunits of the receptor. PMID- 17285632 TI - Analycys: a database for conservation and conformation of disulphide bonds in homologous protein domains. AB - Disulphide bonds in proteins are known to play diverse roles ranging from folding to structure to function. Thorough knowledge of the conservation status and structural state of the disulphide bonds will help in understanding of the differences in homologous proteins. Here we present a database for the analysis of conservation and conformation of disulphide bonds in SCOP structural families. This database has a wide range of applications including mapping of disulphide bond mutation patterns, identification of disulphide bonds important for folding and stabilization, modeling of protein tertiary structures and in protein engineering. The database can be accessed at: http://bioinformatics.univ reunion.fr/analycys/. PMID- 17285633 TI - Measurement of antigen specific immune responses: 2006 update. AB - Measuring antigen-specific immune responses (MASIR) is essential for basic immunological research and in the clinical setting. Numerous techniques have been used and the recent years have witnessed a flourishing of flow cytometry based methods for the identification of antigen specific T cells, in addition to other methodologies. The second MASIR conference held in Santorini, Greece, from 14 to 18 June 2006 has been a forum for the discussion of methodological issues and for research or clinical applications of these techniques, as reviewed here. In addition to flow cytometry based techniques, other emerging techniques with different degrees of complexity can be applied. These novel methods are highly promising in numerous conditions to look for correlates of protection, to test responses to natural infections or to vaccination trials, to evaluate the immune status of immunocompromised patients and to monitor persistence and function of specific T cells administered as adoptive therapy. PMID- 17285634 TI - Mechanistic events underlying odorant binding protein chemoreception. AB - Odorant binding proteins (OBP's) are small hydrophilic proteins, belonging to the lipocalin family dedicated to bind and transport small hydrophobic ligands. Despite many works, the mechanism of ligand binding, together with the functional role of these proteins remains a topic of debate and little is known at the atomic level. The present work reports a computational study of odorants capture and release by an OBP, using both constrained and unconstrained simulations, giving a glimpse on the molecular mechanism of chemoreception. The residues at the origin of the regulation of the protein door opening are identified and a tyrosine amino-acid together with other nearby residues appear to play a crucial role in allowing this event to occur. The simulations reveal that this tyrosine and the protein's L5 loop are implicated in the ligand contact with the protein and act as an anchoring point for the ligand. The protein structural features required for the ligand entry are highly conserved among many transport proteins, suggesting that this mechanism could somewhat be extended to some members of the larger family of lipocalin. PMID- 17285635 TI - Evolution of gastrulation in the ray-finned (actinopterygian) fishes. AB - Sometime before or during the early Mesozoic era, new lineages of actinopterygian (ray-finned) fishes radically transformed their mode of gastrulation. During this evolutionary transformation, yolky endoderm was a hotspot for ontogenetic change. As holoblastic cleavage patterns were modified into meroblastic cleavage patterns, major changes in cell identity specification occurred within the mesendodermal marginal zone, as well as in the superficial epithelium of the embryo. These cellular identity changes resulted in the appearance of two novel extra-embryonic tissues within the embryos of teleostean fishes: the enveloping layer (EVL) and the yolk syncytial layer (YSL). The generation of these extra embryonic tissues prompted major morphogenetic changes within the Organizer Region. As these evolutionary changes occurred, the outermost cell layer of the Organizer (the Organizer Epithelium) was apparently retained as a signaling center necessary for the establishment of left-right embryonic asymmetry in the embryo. Conserved and derived features of Organizer morphogenesis and gastrulation within ancient lineages of ray-finned fishes provide important insights into how the genetically encoded cell behaviors of early morphogenesis can be altered during the course of evolution. In particular, a highly divergent form of actinopterygian gastrulation, which is found in the annual fishes of South America, demonstrates that no aspect of vertebrate gastrulation is inherently immutable to evolutionary change. PMID- 17285636 TI - The ligand Jelly Belly (Jeb) activates the Drosophila Alk RTK to drive PC12 cell differentiation, but is unable to activate the mouse ALK RTK. AB - The Drosophila Alk receptor tyrosine kinase (RTK) drives founder cell specification in the developing visceral mesoderm and is crucial for the formation of the fly gut. Activation of Alk occurs in response to the secreted ligand Jelly Belly. No homologues of Jelly Belly are described in vertebrates, therefore we have approached the question of the evolutionary conservation of the Jeb-Alk interaction by asking whether vertebrate ALK is able to function in Drosophila. Here we show that the mouse ALK RTK is unable to rescue a Drosophila Alk mutant, indicating that mouse ALK is unable to recognise and respond to the Drosophila Jeb molecule. Furthermore, the overexpression of a dominant-negative Drosophila Alk transgene is able to block the visceral muscle fusion event, which an identically designed dominant-negative construct for the mouse ALK is not. Using PC12 cells as a model for neurite outgrowth, we show here for the first time that activation of dAlk by Jeb results in neurite extension. However, the mouse Alk receptor is unable to respond in any way to the Drosophila Jeb protein in the PC12 system. In conclusion, we find that the mammalian ALK receptor is unable to respond to the Jeb ligand in vivo or in vitro. These results suggest that either (i) mouse ALK and "mouse Jeb" have co-evolved to the extent that mALK can no longer recognise the Drosophila Jeb ligand or (ii) that the mALK RTK has evolved such that it is no longer activated by a Jeb-like molecule in vertebrates. PMID- 17285637 TI - Growth plate formation and development in alligator and mouse metapodials: evolutionary and functional implications. AB - Mammalian metapodials (metacarpals and metatarsals), unlike most long bones, form a single growth plate, and undergo longitudinal growth at only one end. The growth dynamics of non-mammalian tetrapod metapodials have not been systematically examined in order to determine if unidirectional growth is unique to mammals. Here we compare murine metapodial ossification in growth stages that parallel those of embryonic, juvenile and subadult American alligators (Alligator mississippiensis). Safranin O staining was used for qualitative histology, and chondrocyte differentiation and proliferation were assessed via immunohistochemistry for type X collagen and proliferative cell nuclear antigen (PCNA). We establish that growth plates form at both ends of alligator metapodials and are maintained in the subadult. PCNA results show that alligators and mice share common patterns of chondrocyte proliferation during growth plate formation. In addition, while alligators and mice differ initially in the degree of organization and pace of chondrocyte differentiation, these parameters are largely similar in established growth plates. However, the replacement of cartilage by bone is highly irregular throughout growth in the alligator, in contrast to the more uniform process in the mouse. These results indicate that while alligators and mammals share common mechanisms of chondrocyte regulation, they differ substantially in their processes of ossification. Phylogenetic analysis indicates that the direct ossification of one epiphysis and reliance on a single growth plate is a derived character (synapomorphy) in therian mammals and likely indicates an adaptation for erect quadrupedal gait. PMID- 17285638 TI - First evidence of chitin as a component of the skeletal fibers of marine sponges. Part I. Verongidae (demospongia: Porifera). AB - The Porifera (sponges) are often regarded as the oldest, extant metazoan phylum, also bearing the ancestral stage for most features occurring in higher animals. The absence of chitin in sponges, except for the wall of peculiar resistance bodies produced by a highly derived fresh-water group, is puzzling, since it points out chitin to be an autapomorphy for a particular sponge family rather than the ancestral condition within the metazoan lineage. By investigating the internal proteinaceous (spongin) skeleton of two demosponges (Aplysina sp. and Verongula gigantea) using a wide array of techniques (Fourier transform infrared (FTIR), Raman, X-ray, Calcofluor White Staining, Immunolabeling, and chitinase test), we show that chitin is a component of the outermost layer (cuticle) of the skeletal fibers of these demosponges. FTIR and Raman spectra, as well as X-ray difractograms consistently revealed that sponge chitin is much closer to the alpha-chitin known from other animals than to beta-chitin. These findings support the view that the occurrence of a chitin-producing system is the ancestral condition in Metazoa, and that the alpha-chitin is the primitive form in animals. PMID- 17285639 TI - Assessing the impact of pollution on the Japaratuba river in Brazil using the Drosophila wing spot test. AB - The Drosophila melanogaster somatic mutation and recombination test (SMART) was used to assess the genotoxicity of surface (S) and bottom (B) water and sediment samples collected from Sites 1 and 2 on the Japaratuba River (Sergipe, Brazil), an area impacted by a petrochemical industrial complex that indirectly discharges treated effluent (produced water) into the river. The genotoxicity tests were performed in standard (ST) cross and high bioactivation (HB) cross flies and were conducted on samples taken in March (dry season) and in July (rainy season) of 2003. Mutant spot frequencies found in treatments with unprocessed water and sediment samples from the test sites were compared with the frequencies observed for similar samples taken from a clean reference site (the Jacarecica River in Sergipe, Brazil) and those of negative (ultrapure water) controls. While samples from the Japaratuba River generally produced greater responses than those from the Jacarecica River, positive responses were detected for both the test and reference site samples. All the water samples collected in March 2003 were genotoxic. In July 2003, the positive responses were restricted to water samples collected from Sites 1 B and 2 S in the ST cross. The genotoxicity of the water samples was due to mitotic recombination, and the samples produced similar genotoxic responses in ST and HB flies. The spot frequencies found in the July water samples were considerably lower than those for the March water samples, suggesting a seasonal effect. The only sediment samples that were genotoxic were from Site 1 (March and July) and from the Jacarecica River (March). The genotoxins in these samples produced both somatic mutation (limited to the Site 1 sample in HB flies) and recombination. The results of this study indicate that samples from both the Japaratuba and Jacarecica Rivers were genotoxic, with the most consistently positive responses detected with Site 1 samples, the site closest to the putative pollution source. PMID- 17285640 TI - Cytotoxicity and genotoxicity of ultrafine crystalline SiO2 particulate in cultured human lymphoblastoid cells. AB - Respirable crystalline silica has been classified as a human lung carcinogen. Ultrafine (diameter < 100 nm) silica particles may be important in carcinogenesis, although the mechanisms remain unclear. In the present study, WIL2-NS cells were incubated for 6, 24, and 48 hr with 0, 30, 60, and 120 microg/ml ultrafine crystalline SiO(2) (UF-SiO(2)). The cytotoxic and genotoxic effects caused by UF-SiO(2) in cultured human cells were investigated via a set of bioassays. Significant dose- dependent decreases in percent cell viability were seen with increasing dose of UF-SiO(2) in the methyl tetrazolium assay. Significant decreases were seen at 120 microg/ml (58, 38, and 57% for 6, 24, and 48-hr exposure, respectively). During 4 days growth in the flasks, there was a slight recovery observed after washing off UF-SiO(2) as measured by the population growth assay. Significant dose-dependent reduction in the cytokinesis block proliferation index was observed by the cytokinesis block micronucleus assay. Treatment with 120 microg/ml UF-SiO(2) for 24 hr produced a fourfold increase in the frequency of micronucleated binucleated cells (MNBNC). The increase in MNBNC was dose-dependent. The lowest dose that gave a statistically significant increase in MNBNC was 30 microg/ml (24-hr treatment), which had cytotoxicity of less than 10%. There was no significant difference in DNA strand breakage as measured by the Comet assay. A significant increase in induced mutant frequency was found at 120 microg/ml as detected by the hypoxanthine guanine phosphoribosyltransferase mutation assay. The results indicate that UF-SiO(2) is cytotoxic and genotoxic in cultured human cells. PMID- 17285641 TI - Cancer cachexia syndrome in head and neck cancer patients: part I. Diagnosis, impact on quality of life and survival, and treatment. AB - BACKGROUND: Cancer cachexia is a debilitating, wasting condition that affects many cancer patients, including those with head and neck cancer. The overall incidence of cancer cachexia is quite high for some types of cancer, and cachexia will be the main cause of death for more than 20% of all cancer patients. This syndrome uniquely challenges patients with head and neck cancer. This article outlines the diagnosis of cancer cachexia, reviews its impact on patient quality of life (QOL) and survival, and updates the reader on potential therapies that may suppress it. METHODS: A comprehensive literature search was performed using PubMed of the National Library of Medicine, which includes more than 15 million citations back to the 1950s. The Cochrane Library and Google search engine were used as well. RESULTS: This syndrome differs significantly from starvation, and thus accurate and timely diagnosis is essential. Nutritional therapy alone is insufficient. Current management strategies include corticosteroids and megesterol acetate, in conjunction with nutritional therapy. Future strategies may include nutraceuticals, omega-3 fatty acids, inflammatory antagonists, and other targeted treatments. CONCLUSIONS: Because cancer cachexia differs significantly from starvation, nutritional supplementation must be used in conjunction with other anti-cachexia agents to reverse the chronic systemic inflammatory state and the effects of circulating tumor-derived factors seen in cachexia. Careful identification of patients at risk and those suffering from this syndrome will lead to better outcomes and treatments. Ultimately, more research is needed to better treat this devastating condition. PMID- 17285642 TI - A single-step photolithographic interface for cell-free gene expression and active biochips. AB - We have developed a biochip platform technology suitable for controlled cell-free gene expression at the micrometer scale. A new hybrid molecule, "Daisy", was designed and synthesized to form in a single step a biocompatible lithographic interface on silicon dioxide. A protocol is described for the immobilization of linear DNA molecules thousands of base pairs long on Daisy-coated surfaces with submicrometer spatial resolution and up to high densities. On-chip protein synthesis can be obtained with a dynamic range of up to four orders of magnitude and minimal nonspecific activity. En route to on-chip artificial gene circuits, a simple two-stage gene cascade was built, in which the protein synthesized at the first location diffuses to regulate the synthesis of another protein at a second location. We demonstrate the capture of proteins from crude extract onto micrometer-scale designated traps, an important step for the formation of miniaturized self-assembled protein chips. Our biochip platform can be combined with elastomeric microfluidic devices, thereby opening possibilities for isolated and confined reaction chambers and artificial cells in which the transport of products and reagents is done by diffusion and flow. The Daisy molecule and described approach enables groups not proficient in surface chemistry to construct active biochips based on cell-free gene expression. PMID- 17285643 TI - NiFe nanoparticles: a soft magnetic material? AB - Polytetrahedral NiFe nanoparticles with diameters of (2.8+/-0.3) nm have been obtained by hydrogenation of Ni[(COD)(2)] (COD=1,5-cyclooctadiene) and Fe[{N(SiMe(3))(2)}(2)] at 150 degrees C using stearic acid and hexadecylamine as stabilizing ligands. The nanoparticles are superparamagnetic at room temperature and display a blocking temperature of 17.6 K. Their anisotropy (2.7x10(5)J m(-3)) is determined to be more than two orders of magnitude higher than that of the bulk NiFe alloy (10(3)J m(-3)) and is close to that determined for Fe nanoparticles of the same size. Still, they display a magnetization of (1.69+/ 0.05) mu(B) per metallic atom, identical to that of the bulk NiFe alloy. Combining the results from X-ray absorption and Mossbauer studies, we evidence a progressive enrichment in iron atoms from the core to the surface of the nanoparticles. These results are discussed in relation to both size and chemical effects. They show the main role played by the enriched Fe surface on the magnetic properties and address the feasibility of soft magnetic materials at the nanoscale. PMID- 17285644 TI - Growth mechanism of truncated triangular III-V nanowires. PMID- 17285645 TI - Fabrication and magnetic functionalization of cylindrical porous anodic alumina. PMID- 17285646 TI - Highly luminescent Cd1-xZnxSe/ZnS core/shell nanocrystals emitting in the blue green spectral range. PMID- 17285647 TI - Addressable, large-area nanoscale organic light-emitting diodes. PMID- 17285648 TI - Purification of semiconducting carbon nanotubes. PMID- 17285649 TI - Blow-up: making sense of the image in the nanoworld. PMID- 17285650 TI - Electrochemiluminescent cells based on zeolite-encapsulated host-guest systems: encapsulated ruthenium tris-bipyridyl. AB - An electrochemiluminescent cell has been developed that has an active layer consisting of ruthenium tris-bipyridyl encapsulated inside zeolite Y supercages. Operation of the cell requires the addition of polyethylene glycol as the solid electrolyte. The cell, which exhibits electrical conductivity behavior typical of a semiconductor, has an optimum operating voltage of 3 V. Ion exchange of sodium by cesium and vapor deposition of calcium metal inside the zeolite pores enhance the electrochemiluminescent efficiency of the cell by a factor of 4. PMID- 17285651 TI - Ferromagnetic interaction in an asymmetric end-to-end azido double-bridged copper(II) dinuclear complex: a combined structure, magnetic, polarized neutron diffraction and theoretical study. AB - A new end-to-end azido double-bridged copper(II) complex [Cu(2)L(2)(N(3))2] (1) was synthesized and characterized (L=1,1,1-trifluoro-7-(dimethylamino)-4-methyl-5 aza-3-hepten-2-onato). Despite the rather long Cu-Cu distance (5.105(1) A), the magnetic interaction is ferromagnetic with J= +16 cm(-1) (H=-JS(1)S(2)), a value that has been confirmed by DFT and high-level correlated ab initio calculations. The spin distribution was studied by using the results from polarized neutron diffraction. This is the first such study on an end-to-end system. The experimental spin density was found to be localized mainly on the copper(II) ions, with a small degree of delocalization on the ligand (L) and terminal azido nitrogens. There was zero delocalization on the central nitrogen, in agreement with DFT calculations. Such a picture corresponds to an important contribution of the d(x2-y2) orbital and a small population of the d(z2) orbital, in agreement with our calculations. Based on a correlated wavefunction analysis, the ferromagnetic behavior results from a dominant double spin polarization contribution and vanishingly small ionic forms. PMID- 17285652 TI - Novel structural motifs consisting of chiral thiazolines: synthesis, molecular recognition, and anticancer activity. AB - The facile synthesis of linear and cyclic chiral oligo(4-alpha/beta methyl)thiazolines is described. Linear oligothiazolines have been efficiently synthesized by the iterative formation of thiazoline rings and two-directional block condensation. The construction of 24- to 36-membered cyclic oligothiazolines was achieved through the head-to-tail cyclo-oligomerization of doubly deprotected linear fragments. Studies of the interactions of both the linear and cyclic oligomers with chiral compounds revealed that cyclic oligomers displayed a strong binding affinity towards mandelic acid, whereas linear oligomers showed a poor affinity. Linear oligomers have been proven to inhibit the cell growth of the cancer cell lines HPAC, PC-3, and HCT-116. Studies of the structure-activity relationships showed that the IC50 values are clearly dependent on both the length and the terminal functionalities of the linear oligomers. Longer derivatives showed more potent activity (e.g., hexi- and octithiazolines exhibit IC50<1 microM) against all three cancer cell lines. In sharp contrast, cyclic oligomers were inactive to all three cell lines. PMID- 17285653 TI - Design of original bioactive formulations based on sugar-surfactant/non-steroidal anti-inflammatory catanionic self-assemblies: a new way of dermal drug delivery. AB - A new kind of catanionic assembly was developed that associates a sugar-based surfactant with a non-steroidal anti-inflammatory drug (NSAID). Three different assemblies using indomethacin, ibuprofen and ketoprofen as NSAIDs were easily obtained in water by an acid-base reaction. These assemblies formed new amphiphilic entities because of electrostatic and hydrophobic effects in water and led to the spontaneous formation of vesicles. These catanionic vesicles were then tested as potential NSAID delivery systems for dermatological application. The anti-inflammatory activity was evaluated in vivo, and this study clearly showed an improved therapeutic effect for NSAIDs that were formulated as catanionic vesicles. These vesicles ensured a slower diffusion of the NSAID through the skin. This release probably increased the time of retention of the NSAID in the targeted strata of the skin. Thus, the present study suggests that this catanionic bioactive formulation could be a promising dermal delivery system for NSAIDs in the course of skin inflammation treatment. PMID- 17285654 TI - Intramolecular excimer formation and delayed fluorescence in sterically constrained pyrene dimers. AB - The synthesis is described for a series of five molecular dyads comprising pyrene based terminals covalently linked through a 1,3-disubstituted phenylene spacer. The extent of through-space communication between the pyrene units is modulated by steric interactions imposed by bulky moieties attached at the 6,8-positions of each pyrene unit. For the control compound, only hydrogen atoms occupy the 6,8 positions (DP1), whereas the remaining compounds incorporate ethynylene groups terminated with either triisopropylsilyl (DP2), 1-tert-butylbenzene (DP3), 2,6-di tert-butylbenzene (DP4) or 1-tert-butyl-3,5-dimethylbenzene (DP5) units. Each compound shows a mixture of monomer and excimer fluorescence in fluid solution at room temperature, but only monomer emission in a glassy matrix at 77 K. The ratio of monomer to excimer fluorescence depends markedly on the molecular structure; DP1 is heavily biased in favour of the excimer and DP4 is enriched with monomer fluorescence. Photophysical properties, including laser induced and delayed fluorescence data, are reported for each compound. Delayed fluorescence occurs by both intramolecular and bimolecular steps, but these events take place on different timescales. The possibility is raised for using intramolecular triplet triplet annihilation as a means of molecular imaging. PMID- 17285655 TI - An optical thermometer based on the delayed fluorescence of C70. AB - A sensitive and broad-ranged optical thermometer, based on the thermally activated delayed fluorescence of fullerene C70, is presented. It consists of C70 molecularly dispersed in a polymer film. Several polymer matrices were investigated. In the absence of oxygen the fluorescence intensity increases markedly with temperature. At 25 degrees C the fluorescence intensity of C70 increases maximally by a factor of between 17 and 22, depending on the polymer, whereas at 100 degrees C the fluorescence intensity can be 79 times higher. In the absence of oxygen and for temperatures above 20 degrees C, the red fluorescence of C70 in the films is so intense that it is easily perceived by the naked eye. For the systems studied, the fluorescence intensity is very sensitive to temperature. This results in a working range from -80 to at least 140 degrees C in the case of C70 in poly(tert-butyl methacrylate) (PtBMA). Perylene was incorporated into the film as an internal reference in order to enable ratiometric measurements. The sensitivity of the lifetime of the delayed fluorescence to temperature is also high and results in an even wider working range. The performance of the C70/PtBMA film was measured against a well-known optical temperature probe, [Ru(phen)3] (phen=phenanthroline). The results show that the C70/PtBMA film is a very good system for optical temperature-sensing over a wide range of temperatures, outperforming known standards. PMID- 17285656 TI - Ultralight conductive carbon-nanotube-polymer composite. PMID- 17285657 TI - Confined diffusion in ordered nanoporous alumina membranes. PMID- 17285658 TI - Model studies on a carprofen derivative as dual photosensitizer for thymine dimerization and (6-4) photoproduct repair. AB - Cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts are among the main UV induced DNA lesions. Both types of damage are mostly repaired in prokaryotes by photolyase enzymes. The repair mechanism of (6-4) photolyases has still not been fully elucidated, but it is assumed that back rearrangement to the oxetane occurs prior to repair. In this work, a non-steroidal anti-inflammatory drug derivative corresponding to the dechlorinated methyl ester of carprofen (namely methyl 2 (carbazol-2-yl)propanoate, PPMe) has been used to achieve the photosensitized cycloreversion of model oxetanes (formally resulting from photocycloaddition between benzophenone and 1,3-dimethylthymine or 2'-deoxyuridine), by employing fluorescence spectroscopy, laser flash photolysis, HPLC and NMR. Although PPMe is able to photoinduce the cycloreversion of both oxetanes, the fluorescence quenching of PPMe is faster for the 2'-deoxyribose-containing oxetane; this underlines the importance of the structure in such studies. Moreover, PPMe was shown to photoinduce the formation of thymidine cyclobutane dimers through a triplet-triplet energy transfer from a vibrationally excited state, as suggested by the enhanced PPMe triplet quenching by thymidine with increasing temperature. These results reveal a dual role of PPMe in DNA photosensitization, in that it photoinduces either damage or repair. PMID- 17285660 TI - A conformational analysis method for understanding the energy landscapes of clusters. AB - A newly developed unbiased structural optimization method, named dynamic lattice searching (DLS), is proposed as an approach for conformational analysis of atomic/molecular clusters and used in understanding the energy landscape of large clusters. The structures of clusters are described in terms of the number of basic tetrahedron (BT) units they contain. We found that the hit numbers of different structural motifs in DLS runs is proportional to the number of BTs. A parameter T(max) is defined to limit the maximal number of atoms moved in a structural transition. Results show that T(max) is a key parameter for modulating the efficiency of the DLS method and has a great influence on the hit number of different motifs in DLS runs. Finally, the effect of potential range on the conformational distribution of the (Morse)(98) cluster is also discussed with different potential-range parameters. PMID- 17285659 TI - Partial (13)C and (15)N chemical-shift assignments of the disulfide-bond-forming enzyme DsbB by 3D magic-angle spinning NMR spectroscopy. AB - DsbB is a 20 kDa Escherichia coli inner-membrane protein that catalyzes disulfide bond formation in periplasmic proteins. We report highly resolved, multidimensional magic-angle spinning NMR spectra at 750 MHz (1)H frequency, which enable partial (13)C and (15)N chemical-shift assignments of the signals. The narrow line widths observed indicate excellent microscopic order of the protein sample, suitable for full structure determination by solid-state NMR. Experiments were performed exclusively on uniformly (13)C,(15)N-labeled DsbB. Chemical-shift-correlation experiments based on dipolar transfer yielded strong signals in the 3D spectra, many of which have been site-specifically assigned to the four transmembrane helices of DsbB. Significant numbers of additional residues have been assigned to stretches of amino acids, although not yet placed in the amino acid sequence. We also report the temperature dependence of signal intensities from -50 degrees C to 0 degrees C, a range over which samples of DsbB are highly stable. Structural and dynamic information derived from SSNMR studies can give insight into DsbB in a state that so far has not been successfully crystallized. PMID- 17285661 TI - Structure-activity study on the spatial arrangement of the third aromatic ring of endomorphins 1 and 2 using an atypical constrained C terminus. AB - The discovery of endomorphins (EMs) has opened the possibility of searching for new analgesics. However, the design of peptide analgesics has proven to be very difficult as a result of their conformational flexibility and a lack of clarity in structure-activity relationships (SAR). In EMs, the amino acid side chains exhibit considerable conformational flexibility, especially in the third aromatic ring, which is free to adopt a bioactive conformation. To resolve these problems, a series of C terminus EM analogues, [Xaa(4)-R]EMs, modified through the substitution of Phe(4) with nonaromatic residues and termination with benzyl groups, were designed to generate conformational constrains of the third aromatic ring by amide bond and torsion angles (phi(4) and psi(4)) of Xaa(4). Introduction of (S)-alpha-methyl or (S)/(R)-alpha-carboxamide on the methylene unit of the benzyl group was designed to produce an atypical topographical constraint (phi(5)) of the third aromatic ring rotation. Interestingly, some EM derivatives, with elimination of the C-terminal carboxamide group and significant changes in the address sequence (Phe(4)-NH(2)), still exhibited higher mu-opioid receptor (MOR) affinity than unmodified EMs. In contrast, some analogues with incorrectly constrained C termini displayed very low affinity and pharmacological activities. Thus, our results indicate that these EM analogues, with atypical constrained C termini, provide model compounds with potent MOR agonism. They also give evidence that the proper spatial orientation and conformational restriction of the third aromatic ring are crucial for the interaction of EMs with MOR. PMID- 17285662 TI - Fabrication of particulate reservoir-containing, capsulelike, and self-folding polymer microstructures for drug delivery. PMID- 17285663 TI - Electronic properties of 3,3'-dimethyl-5,5'-bis(1,2,4-triazine): towards design of supramolecular arrangements of N-heterocyclic Cu(I) complexes. AB - A new efficient and safe synthesis of 3,3'-dimethyl-5,5'-bis-(1,2,4-triazine) is presented. The electron-density distribution and electrostatic properties (charge, electrostatic potential) of this molecule were analyzed. These properties were derived from a high-resolution single-crystal X-ray diffraction experiment at 100 K and compared to the results obtained from ab initio DFT quantum-mechanical calculations. Comparisons of its electrostatic potential features and integrated atomic charges (quantum theory of atoms in molecules, QTAIM) have been made with those of related molecules such as bipyrimidine ligands. Two methods were used to derive integrated charges: one is based on the conventional analytical procedure and the second uses a steepest-ascent numerical algorithm. Excellent agreement was obtained between these two methods. Charges and electrostatic potential were used as predictive indices of metal chelation and discussed in the light of complexation abilities of the title compound and related molecules. The crystal structure of a Cu(I) complex of 3,3'-dimethyl-5,5' bis(1,2,4-triazine) is reported here. In the solid state, this complex forms a three-dimensional multibranch network with open channels in which counterions and solvent molecules are located. This architecture involves both cis and trans isomers of the title compound. PMID- 17285664 TI - Demonstration of promoted zinc Schlenk equilibria, their equilibrium values and derived reactivity. AB - The presence of promoted Schlenk equilibria for organozinc halide species has been explicitly demonstrated by 13C NMR studies. Thus, addition of methylaluminoxane (MeAlO)n, MAO, to RZnX (R=Et, Bn, ArCH2, (CH2)3CO2Et; X=Cl, Br) leads to the formation of ZnR2 and ZnX2MAO. For EtZnCl, equilibration of ZnEt2 and ZnX2MAO is rapid at -35 degrees C; a K value of 0.19 M-1 indicates the equilibrium favours ZnEt2 (0.75-3.0 equiv MAO). Use of RZnX/MAO mixtures allows copper-catalysed 1,4-addition to 2-cyclohexenone to be achieved, but a competing cascade reaction (two subsequent Michael additions and an intramolecular aldol reaction) leads to novel tetracyclic by-products (characterised crystallographically in one case). Activation of EtZnCl is also achieved by ZnMe2 addition and the presence of intermediate EtZnMe was observed by 13C NMR spectroscopy (at equilibrium, K approximately 1). Asymmetric conjugate addition in this system can be realised (up to 92% ee for additions to 2-cyclohexenone). PMID- 17285665 TI - Dehydroiodination of iodo- and diiodomethane by a transient phosphinidene complex. PMID- 17285666 TI - Scanning electrochemical microscopy for direct imaging of reaction rates. AB - Not only in electrochemistry but also in biology and in membrane transport, localized processes at solid-liquid or liquid-liquid interfaces play an important role at defect sites, pores, or individual cells, but are difficult to characterize by integral investigation. Scanning electrochemical microscopy is suitable for such investigations. After two decades of development, this method is based on a solid theoretical foundation and a large number of demonstrated applications. It offers the possibility of directly imaging heterogeneous reaction rates and locally modifying substrates by electrochemically generated reagents. The applications range from classical electrochemical problems, such as the investigation of localized corrosion and electrocatalytic reactions in fuel cells, sensor surfaces, biochips, and microstructured analysis systems, to mass transport through synthetic membranes, skin and tissue, as well as intercellular communication processes. Moreover, processes can be studied that occur at liquid surfaces and liquid-liquid interfaces. PMID- 17285667 TI - Positron emission tomography (PET) and microfluidic devices: a breakthrough on the microscale? PMID- 17285668 TI - The crucial role of the f electrons in the bent or linear configuration of uranium cyanido metallocenes. PMID- 17285669 TI - Highly selective Na(+)-templated formation of [2]pseudorotaxanes exhibiting significant optical outputs. PMID- 17285670 TI - Rhodium-catalyzed cycloisomerization: formation of indoles, benzofurans, and enol lactones. PMID- 17285671 TI - In vitro and intracellular production of peptide-encapsulated fluorescent silver nanoclusters. PMID- 17285673 TI - Looking beyond the RNA structural neighborhood for potentially primordial genetic systems. PMID- 17285672 TI - Development of a cy3-labeled glucose bioprobe and its application in bioimaging and screening for anticancer agents. PMID- 17285674 TI - Meisenheimer complexes positively characterized as stable intermediates in the gas phase. PMID- 17285675 TI - Functionalization of catalase for a photochemical immobilization on poly(ethylene terephthalate). AB - The enzyme catalase (EC 1.11.1.6) was covalently immobilized on textile carrier fabrics made of poly(ethylene terephthalate) (PET) by a novel combined wet chemical and photochemical process. The functionalization of catalase with allyl groups succeeds in a wet chemical treatment of the enzyme with allylglycidylether. This modified enzyme was bonded covalently to the textile material by a photochemical immobilization using a monochromatic excimer UV lamp (222 nm). Using this two-step procedure nearly 60 mg enzyme/g carrier could be fixed durably. The efficiency of the immobilization products was investigated by measuring the enzymatic decomposition of hydrogen peroxide in comparison to the free enzyme. The relative activity of the catalase after the immobilization was nearly 5% compared to the free, not fixed enzyme; however, even after 30 reuses, the modified and immobilized catalase still showed a distinct activity. PMID- 17285676 TI - Plant genomic DNA isolation: an art or a science. AB - Isolating quality DNA from tissues/cells presents a variety of problems in particular when plants are used as the source material. The specific characteristics of plants like the presence of rigid polysaccharide cell wall, pigments, chemical heterogeneity of secondary metabolites found in diverse species of plants, etc., necessitate special consideration and skill during isolation procedure. Until now, numerous protocols have been published for the purpose, but none is found to be universally applicable. Various factors starting from the selection of source material to the concentration of metabolites present in the plant decide the course of the isolation procedure. The present review is an update of various methods used for plant genomic DNA isolation, and it epitomizes the various problems faced and the solutions made to contend with them during DNA isolation from plant cells. PMID- 17285677 TI - PCR amplification on magnetic nanoparticles: application for high-throughput single nucleotide polymorphism genotyping. AB - A novel approach for the genotyping of single nucleotide polymorphisms (SNPs) based on solidphase PCR on magnetic nanoparticles (MNPs) is described. PCR products were amplified directly on MNPs. The genotypes of a given SNP were differentiated by hybridization with a pair of allele-specific probes labeled with dual-color fluorescence (Cy3, Cy5). The results were analyzed by scanning the microarray printed with the denatured fluorescent probes on an unmodified glass slide. Electrophoresis analysis indicated that PCR could proceed successfully when MNPs-bound primers were used. Furthermore, nine different samples were genotyped and their fluorescent signals were quantified. Genotyping results showed that three genotypes for the locus were very easily discriminated. The fluorescent ratios (match probe:mismatch probe signal) of homozygous samples were over 9.3, whereas heterozygous samples had ratios near 1.0. Without any purification and concentration of PCR products, this new MNP-PCR based genotyping assay potentially provides a rapid, labor-saving method for genotyping of a large number of individuals. PMID- 17285678 TI - Bovine fetal microchimerism in normal and embryo transfer pregnancies and its implications for biotechnology applications in cattle. AB - Fetal cells and DNA have been detected in the maternal circulation during and after pregnancy in a few mammalian species. The incidence of similar microchimerism in cattle could have repercussion for the application of modern biotechnologies such as the transfer of transgenic embryos. To determine if feto maternal leakage can occur in pregnant cows, we have analyzed maternal blood samples for the presence of fetal DNA during gestation and post-partum periods. Y chromosome-specific DNA was detected in up to 73% of blood samples from naturally mated heifers carrying conventional bull calves and a transgene-specific sequence in up to 50% of recipient cows carrying transgenic fetuses. These findings document for the first time that transplacental leakage of fetal DNA into the maternal circulation can occur in cattle despite the epitheliochorial placenta of ruminants, with potential implications for the utilization of recipient cows in the food chain. PMID- 17285679 TI - Process development for the production of prebiotic galacto-oligosaccharides from lactose using beta-galactosidase from Lactobacillus sp. AB - Galacto-oligosaccharides (GOS) are formed from lactose in discontinuous mode of conversion using beta-galactosidase from Lactobacillus sp. (beta-gal). The discontinuous process was optimized for technical application with regard to GOS yield, enzyme preparation, reaction temperature and substrate source. It proved to be advantageous to directly apply the crude cell-free enzyme extract for the conversion, since similar GOS yields and composition were obtained as when using the pure enzyme preparation, but expensive purification could be avoided. Reaction temperature was lowered to 17 degrees C to limit microbial contamination when using technical substrates. Thereby GOS yield decreased from 30% to 28% of total sugars and enzyme demand increased 2.7-fold. Whey permeate was compared to buffered lactose solution as a substrate source. The initial reaction rate was found to be 1.8 times higher for the whey permeate substrate; however, GOS yield was slightly lower (approximately 25% of total sugar at 17 degrees C) mainly due to smaller amounts of allolactose[beta-D-Galp-(1-->6)-D-Glc] and the trisaccharide beta-D-Galp-(1-->6)-D-Lac formed. PMID- 17285680 TI - Enantioselective reduction of pentoxifylline to lisofylline using whole-cell Lactobacillus kefiri biotransformation. AB - Lisofylline (LSF) is a drug candidate that has been under investigation for acute respiratory distress syndrome, acute lung injury, septic shock and mucositis. As LSF is not commercially available in our country, we produced it for pharmacokinetic studies. In the present work whole-cell reduction of pentoxifylline [1-(5-oxohexyl)-3,5-dimethylxanthine] to LSF [1-(5R-hydroxyhexyl) 3,5-dimethylxanthine] using Lactobacillus kefiri DSM 20587 was investigated. Glucose or 2-propanol was used as a co-substrate to regenerate the NADPH cofactor. The reaction conditions were optimized. The influence of different concentrations of co-substrates on the yield and enantioselectivity of the biotransformation of pentoxifylline into LSF were tested. Maximum yield (100%) of biotransformation was reached in the presence of glucose as a co-substrate. At glucose concentrations of 675 and 900 mM the bioreduction of pentoxifylline proceeded highly enantioselectively (enantiomeric excess for the R enantiomer of 98%). PMID- 17285682 TI - MRI of intravenously injected bone marrow cells homing to the site of injured arteries. AB - The aim of this study was to test the feasibility of using MRI to detect magnetically labeled, intravenously injected bone marrow (BM) cells homing to injured arteries. In the first phase, BM cells from LacZ-transgenic or green fluorescent protein (GFP)-transgenic mice were transplanted into eight recipient mice. The left femoral arteries of recipient mice were injured using a cuff constriction or endothelium-damage approach, and the right femoral arteries were uninjured to serve as controls. The location and distribution of migrated LacZ-BM or GFP-BM cells were confirmed with histology. In the second phase, BM-derived cells from LacZ-transgenic mice were labeled with superparamagnetic iron oxide (Feridex) and then transplanted into eight recipient mice with cuff-induced injuries in the left femoral arteries. Migrated Feridex/LacZ-BM cells were monitored in vivo using a 4.7 T MR scanner. Subsequently, high-resolution ex vivo MRI was performed on 9.4 T and 11.7 T. LacZ-positive or GFP-positive cells in the thickened adventitia of the injured arteries were evident on histology. Both in vivo and ex vivo MRI showed larger regions of hypointensity with Feridex-labeled cells at the sites of the injured arteries compared with control arteries (P < 0.01). This study provides initial evidence that may support the potential use of MRI to detect homing of intravenously injected BM cells to injured arteries. PMID- 17285683 TI - Measuring and maximizing coverage in the World Trade Center Health Registry. AB - The World Trade Center Health Registry (WTCHR) is a database for following people who were exposed to the disaster of 11 September 2001. Hundreds of thousands of people were exposed to the immense cloud of dust and debris, the indoor dust, the fumes from persistent fires, and the mental trauma of the terrorist attacks on the WTC on 9/11. The purpose of the WTCHR is to evaluate the potential short- and long-term physical and mental health effects of the disaster. The definitions of the exposed groups are broad and defined based on an understanding of which groups had the highest exposures to the WTC disaster and its aftermath. The four exposure groups include rescue and recovery workers, residents, students and school staff, and building occupants and passersby in Lower Manhattan. While one goal of the WTCHR was to maximize coverage overall and for each exposure group, another was to ensure equal representation within exposure groups. Because of the multiple sample types pursued, several approaches were required to determine eligibility. Estimates of the number of eligible persons in each of the exposed populations were based on the best available information including Census, entity specific employment figures, and public and private school enrollment data, among other publicly available sources. To address issues of undercoverage and overcoverage a variety of methods were assessed or applied, including a capture recapture analyses test of overlapping sample building list sources and automated deduplication of sample records. Estimates of the true eligible population indicate that over 400,000 unique individuals were eligible for the baseline health survey. Interviewer-administered surveys were completed with more than 71,000 persons, resulting in an overall enrollment rate of approximately 17 per cent. Coverage was highest among rescue and recovery workers, followed by residents, students and school staff, and building occupants. Both the accuracy of coverage estimates and the raw number and representativeness of enrollees were maximized by our approach to coverage. In designing a registry which relies on multiple pathways and sources of data to build the sample, it is important to develop a comprehensive approach that considers all sources of error and minimizes bias that may be introduced through the methodology. PMID- 17285684 TI - Different attitudes of Chinese patients and their families toward truth telling of different stages of cancer. AB - OBJECTIVE: Cancer patients and their families differed in their attitude toward truth telling. The objective is to investigate different attitudes of Chinese patients or families toward whether and how to disclose diagnosis to patients with different stages of cancer and to examine the difference between the two groups. METHODS: A questionnaire was delivered to 1023 participants. RESULTS: Three hundred and eighty-two patients and 482 families completed the questionnaire. Cancer patients were more likely than families to believe that patient should be informed of the diagnosis (early-stage, 90.8 vs 69.9%, P<0.001; terminal stage, 60.5 vs 34.4%, P<0.001), and that doctor-in-charge was the appropriate person to disclose the diagnosis. Most participants thought that patient should be disclosed immediately after the diagnosis. Nearly half of participants reported that patient should be disclosed in a quiet and undisturbed room. When the hypothetic diagnosis changed from early-stage cancer to terminal illness, the number of participants, who wanted patient to know the diagnosis, decreased significantly. CONCLUSION: Our findings indicated that Chinese cancer patients and their families differed in their attitude toward truth telling and the attitudes toward such a disclosure were influenced by disease stage. Physicians should realize this phenomenon and pay more attention to the skills of how to disclose the cancer diagnosis. PMID- 17285685 TI - Expression and distribution of N-acetyl and N-glycolylneuraminic acids in secreted and cell-associated glycoconjugates by two human osteosarcoma cell lines. AB - N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the dominant sialic acids (Sia) in mammals usually found in the non-reducing terminal of oligosaccharide side chains in glycoproteins and glycolipids. Their expression and distribution pattern have been correlated both with the malignant phenotype and tumor grade of human cancers. The aim of the present study was to determine by reversed-phase HPLC method the amounts of Neu5Ac and Neu5Gc as well as their distribution among the culture media and cell surface of MG-63 and Saos-2 human osteosarcoma cell lines of high and low metastatic potential. It was determined that MG-63 cells produce up to 5-fold more total sialic acid as compared with the Saos 2 cells. Neu5Ac accounts for ca 60% of the total sialic acids secreted by MG 63 cells, whereas Neu5Gc is the predominant sialic acid present on the MG-63 cell membrane. Saos 2 cells secrete considerable amounts of Neu5Ac to culture media. The obtained data indicate that the human osteosarcoma cells express both forms of Sia-containing glycoconjugates; the differences in the amounts of each of the two major Sia types and their distribution may be related to their differences in morphology and/or metastatic potentials. PMID- 17285686 TI - Clustering of stored memories in an attractor network with local competition. AB - In this paper we study an attractor network with units that compete locally for activation and we prove that a reduced version of it has fixpoint dynamics. An analysis, complemented by simulation experiments, of the local characteristics of the network's attractors with respect to a parameter controlling the intensity of the local competition is performed. We find that the attractors are hierarchically clustered when the parameter of the local competition is changed. PMID- 17285687 TI - Computer simulation study on central pattern generator: from biology to engineering. AB - Central pattern generator (CPG) is a neuronal circuit in the nervous system that can generate oscillatory patterns for the rhythmic movements. Its simplified format, neural oscillator, is wildly adopted in engineering application. This paper explores the CPG from an integral view that combines biology and engineering together. Biological CPG and simplified CPG are both studied. Computer simulation reveals the mechanism of CPG. Some properties, such as effect of tonic input and sensory feedback, stable oscillation, robustness, entrainment etc., are further studied. The promising results provide foundation for the potential engineering application in future. PMID- 17285688 TI - Sentence alignment using feed forward neural network. AB - Parallel corpora have become an essential resource for work in multi lingual natural language processing. However, sentence aligned parallel corpora are more efficient than non-aligned parallel corpora for cross language information retrieval and machine translation applications. In this paper, we present a new approach to align sentences in bilingual parallel corpora based on feed forward neural network classifier. A feature parameter vector is extracted from the text pair under consideration. This vector contains text features such as length, punctuate score, and cognate score values. A set of manually prepared training data has been assigned to train the feed forward neural network. Another set of data was used for testing. Using this new approach, we could achieve an error reduction of 60% over length based approach when applied on English-Arabic parallel documents. Moreover this new approach is valid for any language pair and it is quite flexible approach since the feature parameter vector may contain more/less or different features than that we used in our system such as lexical match feature. PMID- 17285689 TI - Robust exponential stabilization of a class of delayed neural networks with reaction-diffusion terms. AB - In this paper, the problem of global robust exponential stabilization for a class of neural networks with reaction-diffusion terms and time-varying delays which covers the Hopfield neural networks and cellular neural networks is investigated. A feedback control gain matrix is derived to achieve the global robust exponential stabilization of the neural networks by using the Lyapunov stability theory, and the stabilization condition can be verified if a certain Hamiltonian matrix with no eigenvalues on the imaginary axis. This condition can avoid solving an algebraic Riccati equation. Finally, a numerical simulation illustrates the effectiveness of the results. PMID- 17285690 TI - Analog VLSI implementation of resonate-and-fire neuron. AB - We propose an analog integrated circuit that implements a resonate-and-fire neuron (RFN) model based on the Lotka-Volterra (LV) system. The RFN model is a spiking neuron model that has second-order membrane dynamics, and thus exhibits fast damped subthreshold oscillation, resulting in the coincidence detection, frequency preference, and post-inhibitory rebound. The RFN circuit has been derived from the LV system to mimic such dynamical behavior of the RFN model. Through circuit simulations, we demonstrate that the RFN circuit can act as a coincidence detector and a band-pass filter at circuit level even in the presence of additive white noise and background random activity. These results show that our circuit is expected to be useful for very large-scale integration (VLSI) implementation of functional spiking neural networks. PMID- 17285691 TI - Kohonen's feature maps for fly ash categorization. AB - Fly ash is a common admixture used in concrete and may constitute up to 50% by weight of the total binder material. Incorporation of fly ash in Portland-cement concrete is highly desirable due to technological, economic, and environmental benefits. This article demonstrates the use of artificial intelligence neural networks for the classification of fly ashes in to different groups. Kohonen's Self Organizing Feature Maps is used for the purpose. As chemical composition of fly ash is crucial in the performance of concrete, eight chemical attributes of fly ashes have been considered. The application of simple Kohonen's one dimensional feature maps permitted to differentiate three main groups of fly ashes. Three one-dimensional feature maps of topology 8-16, 8-24 and 8-32 were explored. The overall classification result of 8-16 topology was found to be significant and encouraging. The data pertaining to 80 fly ash samples were collected from standard published works. The categorization was found to be excellent and compares well with Canadian Standard Association's [CSA A 3000] classification scheme. PMID- 17285692 TI - A novel global exponential stability result for discrete-time cellular neural networks with variable delays. AB - Global exponential stability is considered for a class of discrete-time cellular neural networks with variable delays. By employing a discrete Halanay inequality, a new result is presented ensuring global exponential stability of the unique equilibrium point of the networks. The result extends and improves the earlier publications due to the fact that it removes some restrictions on the delay. An example is given to illustrate the effectiveness of the global exponential stability condition provided here. PMID- 17285693 TI - Relaxed stability conditions for delayed recurrent neural networks with polytopic uncertainties. AB - This paper investigates the problem of stability analysis for recurrent neural networks with time-varying delays and polytopic uncertainties. Parameter dependent Lypaunov functionals are employed to obtain sufficient conditions that guarantee the robust global exponential stability of the equilibrium point of the considered neural network. The derived stability criteria are expressed in terms of a set of relaxed linear matrix inequalities, which can be easily tested by using commercially available software. Two numerical examples are provided to demonstrate the effectiveness of the proposed results. PMID- 17285694 TI - [For real asthma control]. PMID- 17285695 TI - [As the heart and coronary vessels grow old]. PMID- 17285696 TI - Getting it right the first time. PMID- 17285697 TI - Profound hypoxia complicating pericardiocentesis. PMID- 17285699 TI - Spotlight: Sir Bruce Keogh, FRCS, MD, KBE. PMID- 17285698 TI - presentation of the 2004 Hermann Wacker Prize to Gisele Soubrane, MD, PhD. PMID- 17285700 TI - The history of cardiopulmonary resuscitation. PMID- 17285701 TI - Abstracts from ESTRO 25. October 8-12, 2006. Leipzig, Germany. PMID- 17285702 TI - Abstracts of the Fourteenth International Conference of the Inflammation Research Association. October 15-19, 2006. Cambridge, Maryland, USA. PMID- 17285703 TI - Abstracts of the 16th Biennial Meeting of the International Society for Developmental Neuroscience. August 24-28, 2006. Banff, Canada. PMID- 17285705 TI - [Something for something--the Hippocratic oath and evidence-based medicine]. PMID- 17285704 TI - Getting a routine checkup. PMID- 17285706 TI - [Proceedings of the 1st Croatian Congress on Arterial Hypertension with International Participation. Zagreb, 9-12 November 2006]. PMID- 17285708 TI - "Whole food" supplements? PMID- 17285707 TI - Viruses from nonhuman primates. PMID- 17285709 TI - "Whole food" supplements? PMID- 17285710 TI - NLRB rules certain charge nurses 'supervisors'. PMID- 17285711 TI - Men and depression. In treatments, attention must be paid to sexual and other issues. PMID- 17285713 TI - When is it epilepsy? PMID- 17285712 TI - Assertive community treatment. PMID- 17285714 TI - Counting your blessings and keeping up with the Joneses. PMID- 17285715 TI - Children of depression. PMID- 17285716 TI - Human pheromones. PMID- 17285717 TI - [Multi-center clinical study of the effect of silver nitrate ointment on the partial-thickness burn wounds]. AB - OBJECTIVE: To evaluate the therapeutic effect of silver nitrate ointment on partial-thickness burn wounds, and observe its side-effects. METHODS: Multi center, randomized, positive drug paralleled self-controlled trial was carried out. Eighty patients with superficial partial-thickness burns, and 40 with deep partial thickness burns were randomized into AgNO3 group and SD-Ag group according to drug topically applied to the wounds. The wound healing time, wound healing rate and bacterial culture of the wound, the effect and safety of the drug, as well as drug irritation to the wounds were studied in these two groups. RESULTS: For the patients with superficial partial-thickness burn wounds, the wound healing time in silver nitrate group was (9.5 +/- 2.7) days, which was obviously shorter than that in SD-Ag group [(10.8 +/- 3.4) days, P <0.01]. The wound healing rate in silver nitrate group on 7 post-burn day ( PBD) was (77.9 +/ 20.5)%, which was obviously higher than that in SD-Ag group [(67.3 +/- 22.6) %, P < 0.01]. For those with deep-partial thickness burn wounds, the wound healing time in silver nitrate group was (21.5 +/- 4.8) days, which was evidently shorter than that in SD-Ag group [(23.3 +/- 6.4) days, P <0.01]. The wound healing rate in silver nitrate group on 20 PBD was (86.6 +/- 15.9)%, which was evidently higher than that in SD-Ag group [(78.5 +/- 17.7)%, P < 0.01]. Silver nitrate ointment has the same antibacterial effect as 1% SD-Ag cream, but it was less painful when applied to the open wounds. CONCLUSION: Silver nitrate ointment is an effective and safe medicament for the clinical management of partial-thickness burn wounds. PMID- 17285719 TI - [An introduction to the hygienic-sanitary situation in the districts of Madrid from the late 19th to the early 20th century]. PMID- 17285720 TI - [The treatise on citruses by Nicolas Monardes]. PMID- 17285721 TI - [Tobacco consumption in Spain in the 18th century]. PMID- 17285722 TI - [Blood in the Liber de Arte Medendi (1564) by Cristobal de Vega (1510-73)]. PMID- 17285723 TI - A new example of a steroid-amino acid hybrid: construction of constrained nine membered D-ring steroids. AB - A new archetype of steroid-amino acid hybrids containing a nine membered D-ring with hetero atoms has been synthesized for the first time from estrone and amino acids by using Yamaguchi coupling reactions. PMID- 17285724 TI - [DMW history: Mozart's ear. From: Deustche Medizinische Wochenscrift 1898; 24: 351-2]. PMID- 17285725 TI - [Medical consultations in 18th-century Spain: reasons for their existence]. PMID- 17285726 TI - [The influence of medieval Spanish alchemy on modern Europe]. PMID- 17285727 TI - [The city in the face of contagion: political measures and administrative dictates in the 1804 yellow fever epidemic in Alicante]. PMID- 17285728 TI - Safety of personnel working in endoscopy units. AB - All personnel performing or assisting with endoscopic procedures and those responsible for reprocessing the equipment should be trained in how to handle the infectious and chemical hazards associated with the endoscopic environment. Endoscopy personnel should follow a comprehensive safety program that outlines the steps individuals should take to prevent injuries from the potential hazards they may encounter in endoscopy units. Safety measures include ensuring that there is adequate lighting and ventilation in the endoscopy unit, cleaning endoscopy instruments thoroughly, and operating equipment safely. PMID- 17285729 TI - The aging heart. PMID- 17285730 TI - [Repentant sinners: the diary of a confessor in 18th-century Asturias]. PMID- 17285731 TI - Medication reconciliation: what every nurse needs to know. PMID- 17285732 TI - [Poverty and literacy: the sick of the General Hospital of Madrid during the reign of Charles III (1759-1788)]. PMID- 17285733 TI - Any given Sunday. Paramedics assist trainers and physicians in the NFL's largest stadium. PMID- 17285734 TI - HIV update. Prehospital risks and prevention methods. PMID- 17285735 TI - Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing. AB - Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with clinical response and prolonged survival in patients with non small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). We began screening patients for somatic EGFR mutations by DNA sequencing as part of clinical care in 2004. We performed a retrospective cohort study of 278 patients with NSCLC referred for EGFR testing over a 10-month period. Tumor samples underwent direct DNA sequence analyses of EGFR exons 18 through 24. We determined the clinical characteristics and EGFR mutation status of the patients and analyzed their response to therapy and survival. EGFR somatic mutations were identified in 68 (24%) of patients. A minimal smoking history was the strongest clinical predictor of harboring a mutation. In multivariable analyses, each pack year of smoking corresponded to a 5% decreased likelihood of having an EGFR mutation. Among 92 patients with unresectable disease undergoing subsequent systemic therapy, EGFR mutations were associated with an increased response rate to EGFR TKIs (p < .0001) but not chemotherapy. Overall survival was significantly prolonged in EGFR mutation-positive patients (p = .001), with a median survival of 3.1 years compared with 1.6 years in mutation-negative patients, after adjusting for age, gender, and stage at diagnosis. Integrating molecular profiling into clinical care is feasible in NSCLC patients and provides useful clinical information. PMID- 17285736 TI - The tests of a leader: becoming the boss. AB - Even for the most gifted individuals, the process of becoming a leader is an arduous, albeit rewarding, journey of continuous learning and self-development. The initial test along the path is so fundamental that we often overlook it: becoming a boss for the first time. That's a shame, because the trials involved in this rite of passage have serious consequences for both the individual and the organization. PMID- 17285737 TI - Costs and benefits of an early-alert surveillance system for hospital inpatients. AB - BACKGROUND: The economic implications of inpatient adverse events and rising healthcare costs have intensified interest in patient safety and the efficient delivery of products and services with cost-saving potential. New technologies may help in this regard but must be evaluated economically as well as clinically and should demonstrate cost-benefit for consideration by payers and providers. One such technology--an automated early-alert system for patient distress--has been developed. Performance data suggest clinical worthiness and warrant economic evaluation of the system. SCOPE: A hospital-perspective analysis was conducted with cost modeling and retrospective data to estimate the economic consequences of deleterious clinical events and the impact of the early-alert system when deployed during routine medical-surgical admissions. The principal outcome was expected per-patient direct costs associated with inpatients falls and cardiopulmonary arrests. Reduction of these clinical events through intelligent surveillance with the early-alert system suggested economic benefits that may offset the cost of the technology. FINDINGS: The expected per-patient direct cost for inpatient falls and cardiopulmonary arrests was 191.73 dollars per hospitalization. Estimated economic benefits associated with early-alert surveillance supported a break-even cost of 14.59 dollars per day for the system. CONCLUSION: This study estimated the impact of the early-alert system on the deleterious clinical and economic consequences of inpatient falls and cardiopulmonary arrests on the medical-surgical ward as well as a break-even cost for the system. Results are limited by retrospective data and cost modeling. Ongoing clinical evaluation is required to quantify and compare more precisely the cost of care with and without the system in real-life clinical settings. In the interim, this study may provide some insight into the components and magnitude of the cost for the cited events and the potential benefits and detriments that offset or contribute to the cost of the early-alert system. Study results can be more accurately specified per hospital using institutional data as inputs in the model. PMID- 17285738 TI - US Pharmacopeia Council of Experts 2005-2010: work plans, new revision approaches, and other enhancements. AB - The United States Pharmacopeial Convention (the USP Convention), which meets at 5 year intervals, last convened in 2005. At that meeting, the Convention membership elected a new Council of Experts for the 2005-2010 cycle. In turn, the Council elected members of Expert Committees charged with updating and revising the United States Pharmacopeia-National Formulary (USP-NF) and developing other authoritative standards and information. As one of their final activities, Expert Committees from the 2000-2005 cycle and USP staff carefully reviewed their work from the 2000-2005 cycle and reexamined the contents of USP-NF. From this comprehensive inventory emerged an updated and more focused new work plan directed toward acquiring missing monographs, updating monographs (typically because of advances in analytical technologies), and attending to General Chapter work (eg, dividing the General Chapter Chromatography <621> into smaller chapters) during the 2005-2010 cycle. Several elements of the work plan also speak to Resolutions adopted at the March 2005 Convention (available at www.usp.org/aboutUSP/resolutions.html) and prior ones as well. Because the work plan involves new approaches that affect both General Chapters (and thus the performance of tests and procedures) and monograph specifications--as well as the function of Pharmacopeial Forum and the introduction of new products--USP expects the plan to have a broad impact. This article briefly reviews some of these anticipated changes, informs constituents about how they can remain updated about progress and upcoming modifications to official texts, and invites participation in the standards-setting process. PMID- 17285739 TI - Optimizing targeted gene delivery: chemical modification of viral vectors and synthesis of artificial virus vector systems. AB - In comparison to classical medicines, gene therapy has the potential to mediate the highest possible level of therapeutic specificity. Every normal or diseased cell can switch on or off a gene expression cassette in a tissue-, disease-, and time-dependent fashion, by use of specific transcription factors that are active only in a given unique situation. In practice, we face the problem in realizing the concept: the delivery of nucleic acids into target cells is very ineffective and presents a formidable challenge. Key issues for future developments include improved targeting, enhanced intracellular uptake, and reduced toxicity of gene vectors. The currently used classes of vectors have complementary characteristics, such as high intracellular efficiency of viral vectors on the one hand and low immunogenicity and greater flexibility of nonviral vectors on the other hand. The merge of viral and nonviral vector technologies is highlighted as an encouraging strategy for the future; concepts include chemically modified viral vectors ("chemo-viruses") and synthesis of virus-like systems ("synthetic viruses"). Examples for the development of vectors toward artificial synthetic viruses are presented. PMID- 17285740 TI - Metabolism of GTI-2040, a phosphorothioate oligonucleotide antisense, using ion pair reversed phase high performance liquid chromatography (HPLC) coupled with electrospray ion-trap mass spectrometry. AB - GTI-2040 is a 20-mer phosphorothioate oligonucleotide, which is complementary to the messenger ribonucleic acid (mRNA) of the R2 subunit of ribonucleotide reductase. This study characterized both the in vivo and in vitro metabolism of GTI-2040. A highly specific ion-pair reversed-phase electrospray ionization (IP RP-ESI) liquid chromatography-mass spectrometry (LC-MS) method was used for the identification of GTI-2040 and metabolites from a variety of biological samples including exonuclease enzyme solutions, plasma, urine, mouse liver/kidney homogenates, and human liver microsomes. Progressively chain-shortened metabolites truncated from the 3' terminal of GTI-2040 were detected in all of the evaluated biological samples. GTI-2040 was found to be a good substrate for 3' but not 5' exonuclease. While the pattern of n-1 chain-shortened 3' exonucleolytic degradation was similar in the mouse liver and kidney homogenates, the latter was found to contain a larger number of shortenmers, the kidneys appeared to possess higher enzymatic reactivity toward GTI-2040. Thus, metabolism of GTI-2040 was found to occur in a variety of biological samples, mainly mediated by the 3' exonuclease. PMID- 17285741 TI - In vitro evaluation of chitosan-EDTA conjugate polyplexes as a nanoparticulate gene delivery system. AB - It was the purpose of this study to evaluate the potential of different molecular weight chitosan-EDTA conjugates as a carrier matrix for nanoparticulate gene delivery systems. Covalent binding of EDTA to more than one chitosan chain provides a cross-linked polymer that is anticipated to produce stabilized particles. pDNA/chitosan-EDTA particles, generated via coazervation, were characterized in size and zeta potential by electrophoretic light scattering and electron microscopy. Stability was investigated at different pH values by enzymatic degradation and subsequent gel retardation assay. Lactate dehydrogenase assay was performed to determine toxicity. Furthermore, transfection efficiency into Caco-2 cells was assessed using a beta-galactosidase reporter gene. Chitosan EDTA produced from low-viscous chitosan with 68% amino groups being modified by the covalent attachment of EDTA showed the highest complexing efficacy resulting in nanoparticles of 43 nm mean size and exhibiting a zeta potential of +6.3 mV. These particles were more stable at pH 8 than chitosan control particles. The cytotoxicity of chitosan-EDTA particles was below 1% over a time period of 4 hours. These new nanoplexes showed 35% improved in vitro transfection efficiency compared with unmodified chitosan nanoparticles. According to these results, the chitosan-EDTA conjugate may be a promising polymer for gene transfer. PMID- 17285742 TI - Development and evaluation of topical formulation containing solid lipid nanoparticles of vitamin A. AB - The purpose of this research was to investigate novel particulate carrier system such as solid lipid nanoparticles (SLN) for topical application of vitamin A palmitate and to study its beneficial effects on skin. Topical gels enriched with SLN of vitamin A were prepared. The solid lipid nanoparticulate dispersion was prepared using high-pressure homogenization technique and was incorporated into polymeric gels of Carbopol, Pemulen, Lutrol, and Xanthan gum for convenient application. The nanoparticulate dispersion and its gels were evaluated for various parameters such as particle size, in vitro drug release, in vitro penetration, in vivo skin hydration, and skin irritation. The solid lipid nanoparticulate dispersion showed mean particle size of 350 nm. Differential scanning calorimetry studies revealed no drug-excipient incompatibility. In vitro release profile of vitamin A palmitate from nanoparticulate dispersion and its gel showed prolonged drug release up to 24 hours, which could be owing to embedment of drug in the solid lipid core. In vitro penetration studies showed almost 2 times higher drug concentration in the skin with lipid nanoparticle enriched gel as compared with conventional gel, thus indicating better localization of the drug in the skin. In vivo skin hydration studies in albino rats revealed increase in the thickness of the stratum corneum with improved skin hydration. The developed formulation was nonirritant to the skin with no erythema or edema and had primary irritation index of 0.00. Thus it can be concluded that SLN represents a promising particulate carrier having controlled drug release, improved skin hydration, and potential to localize the drug in the skin with no skin irritation. PMID- 17285743 TI - Preparation and characterization of pluronic-colloidal silicon dioxide composite particles as liquid crystal precursor. AB - The purpose of this study was to produce spray-dried Pluronic-colloidal silicon dioxide (Aerosil) composite particles as a liquid crystal precursor that would form a liquid crystalline phase upon hydration. A Pluronic-colloidal silicon dioxide dispersion in isopropyl alcohol was spray-dried to obtain composite particles using different concentrations of Aerosil. Polarizing microscopy, gelation, gel melting, and rheological studies were employed to characterize the composite particles. The composite particles obtained were irregular, with concave depression. Gelation was found to decrease with the addition of Aerosil, while gel melting was found to increase with the concentration of Aerosil. Rheological studies showed an increase in elasticity as well as viscosity with an increase in the concentration of Aerosil. Composite particles showed improved gelation and rheological properties. These composite particles and the process by which they were obtained may be useful for designing various drug delivery systems. PMID- 17285744 TI - Evaluation of manometric temperature measurement, a process analytical technology tool for freeze-drying: part II measurement of dry-layer resistance. AB - The purpose of this work was to study the factors that may cause systematic errors in the manometric temperature measurement (MTM) procedure used to determine product dry-layer resistance to vapor flow. Product temperature and dry layer resistance were obtained using MTM software installed on a laboratory freeze-dryer. The MTM resistance values were compared with the resistance values obtained using the "vial method." The product dry-layer resistances obtained by MTM, assuming fixed temperature difference (DeltaT; 2 degrees C), were lower than the actual values, especially when the product temperatures and sublimation rates were low, but with DeltaT determined from the pressure rise data, more accurate results were obtained. MTM resistance values were generally lower than the values obtained with the vial method, particularly whenever freeze-drying was conducted under conditions that produced large variations in product temperature (ie, low shelf temperature, low chamber pressure, and without thermal shields). In an experiment designed to magnify temperature heterogeneity, MTM resistance values were much lower than the simple average of the product resistances. However, in experiments where product temperatures were homogenous, good agreement between MTM and "vial-method" resistances was obtained. The reason for the low MTM resistance problem is the fast vapor pressure rise from a few "warm" edge vials or vials with low resistance. With proper use of thermal shields, and the evaluation of DeltaT from the data, MTM resistance data are accurate. Thus, the MTM method for determining dry-layer resistance is a useful tool for freeze drying process analytical technology. PMID- 17285745 TI - Physicochemical characterization of the freezing behavior of mannitol-human serum albumin formulations. AB - The goal of the study was to analyze the impact of human serum albumin (HSA) quality (stabilized or nonstabilized HSA), the addition of NaCl, and the HSA stabilizers Na-octanoate and Na-N-acetyltryptophanate on the freezing behavior of mannitol-HSA formulations. The focus was on crystallization, Tg' (glass transition temperature of the maximally freeze-concentrated phase), and Tc (collapse temperature). Differential scanning calorimetry (DSC), cryomicroscopy, and low-temperature x-ray powder diffraction (LTXRD) were used to study the frozen state. In mannitol-HSA formulations, mannitol crystallization was inhibited and Tg' lowered to a greater extent by stabilized HSA (containing Na octanoate, Na-N-acetyltryptophanate, and NaCl) than by unstabilized HSA. Detailed DSC and LTXRD studies showed that in the concentrations used for stabilizing HSA, NaCl led to changes in the freezing behavior, an effect that was less pronounced for the other stabilizers. NaCl further lowered the Tc, which was determined by cryomicroscopy. As the freezing behavior governs the lyophilization process, the changes have to be taken into consideration for the development of a lyophilization cycle, to avoid collapse and instabilities. PMID- 17285746 TI - Evaluation of manometric temperature measurement (MTM), a process analytical technology tool in freeze drying, part III: heat and mass transfer measurement. AB - This article evaluates the procedures for determining the vial heat transfer coefficient and the extent of primary drying through manometric temperature measurement (MTM). The vial heat transfer coefficients (Kv) were calculated from the MTM-determined temperature and resistance and compared with Kv values determined by a gravimetric method. The differences between the MTM vial heat transfer coefficients and the gravimetric values are large at low shelf temperature but smaller when higher shelf temperatures were used. The differences also became smaller at higher chamber pressure and smaller when higher resistance materials were being freeze-dried. In all cases, using thermal shields greatly improved the accuracy of the MTM Kv measurement. With use of thermal shields, the thickness of the frozen layer calculated from MTM is in good agreement with values obtained gravimetrically. The heat transfer coefficient "error" is largely a direct result of the error in the dry layer resistance (ie, MTM-determined resistance is too low). This problem can be minimized if thermal shields are used for freeze-drying. With suitable use of thermal shields, accurate Kv values are obtained by MTM; thus allowing accurate calculations of heat and mass flow rates. The extent of primary drying can be monitored by real-time calculation of the amount of remaining ice using MTM data, thus providing a process analytical tool that greatly improves the freeze-drying process design and control. PMID- 17285747 TI - Tracking of the kinetic stability of 2 types of total nutrient admixtures containing different lipid emulsions. AB - The physical stability of 2 types of total nutrient admixtures was studied as a function of storage time and temperature. One of them contained only structured triglycerides and the other exclusively long-chain triglycerides as lipid components. To evaluate the possible changes in the kinetic stability of the emulsions and in the surface characteristics of the droplets during storage, particle size analysis, zeta potential, and dynamic surface tension measurements were performed. To follow any chemical decomposition processes that occurred during storage, the pH of the emulsions was also monitored. The mean droplet size of emulsions prepared with lipids containing exclusively long-chain triglycerides showed a remarkable increase after 4 days of storage, in contrast with that of the mixtures containing structured lipids. A combination of size distribution, zeta potential, and dynamic surface tension measurements proved to be useful for an adequate tracking of the kinetic stability of total nutrient admixtures. Structured triglycerides not only provide advantageous metabolic effects but improve the physical stability of total parenteral nutrition admixtures. PMID- 17285748 TI - Scale-up of a pan-coating process. AB - The purpose of this work was to develop a practical scale-up model for a solvent based pan-coating process. Practical scale-up rules to determine the key parameters (pan load, pan speed, spray rate, air flow) required to control the process are proposed. The proposed scale-up rules are based on a macroscopic evaluation of the coating process. Implementation of these rules does not require complex experimentation or prediction of model parameters. The proposed scale-up rules were tested by conducting coating scale-up and scale-down experiments on 24 inch and 52-inch Vector Hi-coaters. The data demonstrate that using these rules led to similar cumulative drug release profiles (f2 >> 50; and P Analysis of Variance [PANOVA] >> 0.05 for cumulative percentage of drug released after 12 hours [Cum12]) from tablets made at 24- and 52-inch scales. Membrane characteristics such as opacity and roughness were also similar across the 2 scales. The effects of the key process variables on coat weight uniformity and membrane characteristics were also studied. Pan speed was found to be the most significant factor related to coating uniformity. Spray droplet size was found to affect the membrane roughness significantly, whereas opacity was affected by the drying capacity. PMID- 17285749 TI - Chargeability measurements of selected pharmaceutical dry powders to assess their electrostatic charge control capabilities. AB - The purpose of this study was to develop an instrument (the Purdue instrument) and the corresponding methodologies to measure the electrostatic charge development (chargeability) of dry powders when they are in dynamic contact with stainless steel surfaces. The system used an inductive noncontact sensor located inside an aluminum Faraday cage and was optimized to measure the charging capabilities of a fixed volume of powder (0.5 cc). The chargeability of 5,5 diphenyl-hydantoin, calcium sulfate dihydrate, cimetidine, 3 grades of colloidal silicon dioxide, magnesium stearate, 4 grades of microcrystalline cellulose, salicylic acid, sodium carbonate, sodium salicylate, spray-dried lactose, and sulfinpyrazone were tested at 4 linear velocities, and the particle size distribution effect was assessed for 3 different grades of colloidal silicon dioxide and 4 different grades of microcrystalline cellulose. The chargeability values exhibited a linear relationship for the range of velocities studied, with colloidal silicon dioxide exhibiting the maximum negative chargeability and with spray-dried lactose being the only compound to exhibit positive chargeability. The instrument sensitivity was improved by a factor of 2 over the first generation version, and the electrostatic charge measurements were reproducible with relative standard deviations ranging from nondetectable to 33.7% (minimum of 3 replicates). These results demonstrate the feasibility of using the Purdue instrument to measure the electrostatic charge control capabilities of pharmaceutical dry powders with a reasonable level of precision. PMID- 17285750 TI - Chitosan gels for the vaginal delivery of lactic acid: relevance of formulation parameters to mucoadhesion and release mechanisms. AB - The aim of this work was to assess the effect of formulation parameters of a mucoadhesive vaginal gel based on chitosan and lactic acid, and to highlight its release mechanisms. Two molecular weight chitosans were used to prepare gels with 2 lactic acid concentrations. Both chitosan molecular weight and lactic acid concentration had a significant and mutually dependent influence on mucoadhesion, measured on pig vaginal mucosa. Similarly, the lactate release profiles were found to be dependent on lactic acid content and polymer molecular weight. One gel formulation based on the stoichiometric lactate to chitosan ratio was subjected to release test in media with 2 different counterions and increasing ionic strength. This test demonstrated that the lactate release is mainly due to ionic displacement. PMID- 17285751 TI - Tracking the physical aging of poly(ethylene oxide): a technical note. PMID- 17285752 TI - Aqueous, oil, and ointment formulations of ketorolac: efficacy against prostaglandin E2-induced ocular inflammation and safety: a technical note. PMID- 17285753 TI - Aggregation of recombinant human interferon alpha 2b in solution: technical note. PMID- 17285754 TI - [Morphology of Parasitengona mites (Acariformes: Parasitengona) and their possible evolutionary scenario]. AB - On the basis of the analysis of morphology and biology of representatives of the Parasitengona, mostly trombiculids, trombidiids and water mites, a new attempt is made to clarify probable evolutionary scenario in this group of the higher trombidiform mites (Actinedida). It is supposed that the very old ancestral group of terrestrial arachnids, having bite-sucking mouth-parts, poorly differentiated sac-like midgut and capability to extra-oral digestion, fed predatory on different small soil arthropods at all phases of the life cycle. They were small segmented orthotrichous homeomorphic arachnids at the rank of genus or family. The favorable feeding conditions of the adult phase have led to the small eggs rich in yolk and the small larva. The latter have led in turn to the necessity of intensive feeding at the larval stage to complete the ontogenesis. Further in evolution, this group gave rise at once to two or even more large paraphyletic branches. Most of them retained feeding on arthropods with transition of larvae to much more effective parasitic feeding provided with the additional specialization of the larval stage. This branch comprise divergently radiated paraphyletic terrestrial and secondary-water water mites each having long course of evolution resulted in the recent groups of Calyptostomatoidea, Erythraeoidea, Trombidioidea and several superfamilies of water mites. Another branch of the ancestral Parasitengona has followed the way of adaptation of larvae to feeding on vertebrates, which were being attacked by the larvae in the environment of pasture. The parasitism on vertebrates has lead to several radical specializations of these mites and their significant evolutionary progress. At the same time, the similar ontogenetic dynamics, as well as synchronous reduction of particular developmental stages in all parasitengones, inevitably indicate the monophyletic origin of the whole branch of Parasitengona with Pterygosomatidae as the most probable sister group. PMID- 17285755 TI - [Species composition and ecological peculiarities of the blood-sucking mosquito genus Ochlerotatus (cantans and dorsalis species groups) (Diptera, Culicidae) in the Novgorod Region]. AB - Seven mosquito species of the genus Ochlerotatus ("cantans" and "dorsalis" species groups, family Culicidae) were found in the Novgorod Region as a result of our field investigations, which have been carried out in 1996-2004. One species, Ochlerotatus annulipes, was for the first time recorded in the Novgorod Region. Distribution, biotopic and seasonal preferences of all discovered species are considered. PMID- 17285756 TI - [Coccidia (Eimeriida) of perciform fishes (Perciformes) in the continental waters of Russia]. AB - Twenty one coccidian species from the genera Eimeria and Goussia are found in the perciform fish hosts from the continental waters of Russia. Names, authors and dates of the species descriptions, synonyms, brief figured description of the morphofunctional organization of the endogenic developmental stages of coccidian, Latin and Russian names of the fish hosts are given. PMID- 17285759 TI - Fundic gland polyps and PPI: the Mozart effect of gastrointestinal pathology? PMID- 17285757 TI - [Indigenous microflora associated with the tegument of Triaenophorus nodulosus (Cestoda) and the intestine of its pike host]. AB - Investigations of the indigenous microflora associated with the mucous intestines of fish and its cestode parasites have been for the first time carried out using the methods of transmission and scanning electron microscopy. New data on the bacterial biodiversity in the cestode and its fish host are obtained. Nanobacteria and spirochaetes are for the first time revealed in a fish host together with the previously known bacteria forming the intestinal microflora of fish. Spirochaetes were shown to be associated with the intestines of a pike host only, while nanobacteria cover abundantly the surface of the apical parts of the intestinal microvilli and the apical parts of the microtriches in the cestode tegument. The similarity of the bacterial floras associated with the apical surface of the parasite tegument and the intestine of the host should be noted. At the same time, deeper bacterial communities represented by obligate symbionts are specific. Thus, there is a normal indigenous microflora in cestodes, associated with the tegumental surface. This symbiotic microflora has specific morphological features and provides the balance of relations in the parasite-host system. PMID- 17285760 TI - Browicz or Kupffer cells? AB - The paper is concerned to problem of discovery of macrofage cells present in the liver sinusoid, which are recognized in the world medical literature as Kuppffer cells. On the other hand in Poland the name of professor Tadeusz Browicz is firmly connected with the cells resulting in eponymous Browicz cells. The authors are trying to determine who has priority in this respect; Karl Kupffer, a professor of anatomy in Koniggsberg, and then in Munchen, or professor of pathological anatomy at Jagiellonian University, Tadeusz Browicz. PMID- 17285761 TI - Analysis of p27KIP1 protein and Ki-67 expression in aggressive fibromatosis (desmoid tumor). AB - Aggressive fibromatosis (desmoid tumor) is an uncommon locally invasive non metastasizing neoplasm lesion. Desmoid tumor consists of fibroblasts, miofibroblasts and a significant amount of extracellular matrix. p27KIP1 (p27) protein is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family that regulates progression through the cell cycle. In various human neoplasms the decreased level of p27 was observed. There were analysed 42 specimens of aggressive fibromatosis, in which there were 24 abdominal and 18 extra-abdominal cases. There was performed immunohistochemical analysis employing a monoclonal antibody against p27 protein and Ki-67 (Novocastra, UK). The sections for immunohistochemical study were stained using the streptavidin - biotin method. The average percentage of cells stained positively for all cases for p27 and Ki-67 was 22.1% (SD=29.2) and 6.0% (SD=8.8) respectively. There was no statistically significant difference between Ki-67 or p27 expression in abdominal and extra-abdominal location. Analysis of p27 and Ki-67 expression levels might indicate that low proliferating activity of desmoid fibroblasts is connected with another mechanism than the one, in which p27 takes part. PMID- 17285762 TI - Immunohistochemical analysis of transforming growth factor beta-1 in AA and AL renal amyloidosis. AB - It has been found that the prognosis of both AA and AL renal amyloidosis is significantly worse in cases in which the renal cortical interstitium exhibits fibrosis at the time of the biopsy than in those in which it is normal. However, the fibrogenic mechanisms operating locally in the kidney are not well understood. Transforming growth factor beta (TGF-P) has been recognized as a key mediator of renal fibrogenesis. Therefore, the present study on AA and AL renal amyloidosis was undertaken to ascertain if potential pathway towards renal tubulointerstitial fibrosis involves TGF-beta and to examine the possible relationship between the immunoexpression of TGF-beta and interstitial alpha smooth muscle actin (alpha-SMA) expression as well as interstitial infiltrates. The mean values of the immunoexpression of TGF-beta-1, interstitial CD3+ cells, alpha-SMA expression as well as interstitial area were in AA and AL groups significantly increased in comparison with controls. The mean values of the interstitial CD68+ cells were in both AA and AL groups increased in comparison with controls however in AL amyloidosis this difference was not significant. Moreover, all investigated parameters were significantly increased in AA group as compared to AL cases. In both AA and AL groups there were significant positive correlations between immunostaining of TGFbeta-1 and alpha-SMA as well as immunostaining of TGF-beta-1 and interstitial volume. In the AA group, a significant negative correlation existed between immunostaining of TGF-beta-1 and CD 3+ cells. In the AL group, this correlation tended to be negative, how ever it did not reach statistical significance. In both AA and AL groups we did not find significant relationship between TGF-beta-1 and interstitial monocytes/macrophages. In conclusion, our study suggests a role of transforming growth factor beta-1 in interstitial fibrotic changes in renal AA and AL amyloidosis and we hypothesize that myofibroblast pathway may be important in this process. PMID- 17285763 TI - Frequency analysis of apoptosis in sporadic breast cancer. AB - The development of breast cancer is associated with an accumulation of specific genetic alterations. These genetic changes affect malignant transformation of both dysregulation of cell proliferation and apoptosis. Apoptotic cell death is a frequent phenomenon in breast cancer. In present work we investigated the association between apoptosis and breast cancer progression. The apoptosis was analysed in breast cancer patients (n=103) in blood and tumour specimens. Blood samples from age matched healthy women served as control (n=90). The apoptosis was detected by special staining techniques TUNEL and by agarose gel electrophoresis. The apoptotic cells were identified in 69.9% (72/103) of the breast cancers and in 1.1% control (1/90). The number of positive samples were significantly higher among cancer samples than among control samples (P < 0.001). There were the significant difference in terminal deoxynucleotide transferase mediated deoxyuridine triphisphate-biotin nick end-labelling index between ductal breast carcinoma and the other histological types. Sex steroid recepor negative tumors have greater apoptotic index than the sex steroid receptor positive ones. The high frequency of apoptotic cells in breast tumours suggests a potential role of apoptosis in cancer appearance and/or progression. PMID- 17285764 TI - Extrapulmonary lymphangioleiomyomatosis presented as the asymptomatic retroperitoneal tumours--two cases report. AB - Lymphangioleiomyomatosis [LAM] is a rare lung disease affecting women and characterized by abnormal smooth muscle cells (LAM cells) proliferation along lung and lymphatic channels. The frequent occurrence of extrapulmonary LAM [e LAM] has been reported as abdomen pelvic lymph nodes involvement, angiomyolipomas, lymphangioleiomyomas or lymphangiomas in LAM patients. An extrapulmonary manifestation as the initial LAM presentation preceding pulmonary disorders and as asymptomatic extrapulmonary LAM lesions are unusual. We report two women presented with asymptomatic retroperitoneal cystic masses accidentally found on ultrasound examination. The tumours were surgically removed and diagnosed as: 1-malignant mesothelioma and 2-tymphangiomyoma. The microscopical sections were reviewed and re-diagnosed as e-LAM at advanced pulmonary LAM development. Mesotheliosis present in e-LAM morphology is unique and was misleading for malignancy diagnosis. The second case illustrates the hormone dependent growth of lymphangiomyoma and LAM development in young women. It is difficult to prove the presence of pulmonary LAM at the time of tumours excision but both cases demonstrate importance of appropriate LAM diagnosis and being aware of such diagnosis in cases presenting with extrapulmonary extension of the disease. PMID- 17285765 TI - Fibroadenoma of the ectopic breast of the axilla--a case report. AB - Polymastia is a term that is used to describe the presence of more than two breasts in human beings. It is synonymous with supernumerary or accessory breast tissue. In the ectopic breast tissue any disease can develop that affects the normal breast, including fibroadenoma. We reported a case of fibroadenoma of the axilla in a 23-year-old woman. Differential diagnosis of an axillary mass should also include fibroadenoma in an ectopic breast tissue. PMID- 17285766 TI - Double cancer of the gallbladder--a case report. AB - The study presented the coexistence of papillary adenocarcinoma and microcellular neuroendocrine carcinoma of the gallbladder in a 56-year old female patient without cholelithiasis and developmental anomalies of the biliary-pancreatic ducts. Considering the material obtained by the authors (94 cases), the above mentioned was diagnosed in 1,06% of gallbladder carcinomas. The authors analyzed literature data and considered pathogenetic factors, responsible for development of two gallbladder carcinomas. PMID- 17285767 TI - [Recording of spontaneous oscillations in the procerebrum of terrestrial mollusk Helix in free behavior]. AB - Procerebrum is the central part of the olfactory system in terrestrial snails. Spontaneous rhythmic oscillations were described in this structure. The role of these oscillations in the mechanisms of odor perception and discrimination is unknown yet. Electrical activity of the Helix procerebrum was recorded in vivo. Changes in spontaneous rhythmic oscillations in response to olfactory stimulation were observed. Within the first 10 s after odor application (cineole) in low concentration, a statistically significant decrease in the frequency and increase in the amplitude of procerebrum oscillations were revealed in freely behaving animals. Timing of those changes corresponded to the time of defensive reaction realization of the tentacle withdrawal. The increase in the amplitude and a tendency to a decrease in the frequency of oscillations in response to odor application in high concentration were observed in time period 11-20 s, which corresponded to an increased duration of tentacle withdrawal. The results suggest an implicit relation of the amplitude and frequency of oscillations in odor perception and discrimination. PMID- 17285768 TI - [Characteristics of attention in children with attention deficit hyperactivity disorder (an analytical review)]. AB - The information concerning specific features of different attention components (alertness, sustention and selectivity) in children with attention deficit hyperactivity disorder (ADHD) is analyzed and systematized. According to the data reviewed, behavioral and attention problems described as ADHD are not homogeneous. Literature analysis of attention characteristics in children with ADHD shows that different components can be disrupted if ADHD is diagnosed as inattentive or combined subtype, but the main deficit in this case is that of selective voluntary attention. In case of hyperactivity/impulsivity subtype of ADHD, attention is impaired mainly in its brain activation components. PMID- 17285769 TI - [A contribution of synaptic plasticity in the basal ganglia to processing of visual information]. AB - The mechanism of involvement of the basal ganglia in processing of visual information on the basis of dopamine-dependent modulation of efficacy of synaptic transmission in interconnected parallel associative and limbic loops (cortex- basal ganglia--thalamus--cortex) is proposed. Each loop consists of one of the visual or prefrontal cortical areas connected with the thalamic nucleus and corresponding loci in different nuclei of the basal ganglia. Circulation of activity in such a loop provides reentrance of information into the thalamus and neocortex. Dopamine releasing in response to a visual stimulus oppositely modulates the efficacy of "strong" and "weak" corticostriatal inputs. Subsequent reorganization of activity in the loop leads to a disinhibition (inhibition) of activity of those cortical neurons that were "strongly" ("weakly)" excited by the visual stimulus simultaneously with activation of dopaminergic cells. A selected neuronal pattern in each cortical area represents a property of the visual stimulus processed by this area. Excitation of dopaminergic cells by the visual stimulus via the superior colliculi requires parallel activation of a disinhibitory input to the superior colliculi via the thalamus and a "direct" pathway through the basal ganglia. The prefrontal cortex excited by the visual stimulus via the mediodorsal thalamic nucleus performs a top-down control over the dopaminergic cell activity, supervising simultaneous dopamine release in different striatal loci and thus promotes the interconnected selection of neuronal representations of individual properties of the visual stimulus and their binding in an integrated image. PMID- 17285770 TI - [Dynamics of P300 component of acoustic evoked potential in postraumatic unconsciousness]. AB - In order to reveal features of the brain reactions to external stimuli in the course of consciousness recovery after a severe craniocerebral injury, component P300 of acoustic evoked potential was analyzed in 9 patients with chronic and 32 patients with reversible unconsciousness. In patients with chronic unconsciousness, P300 parameters displayed a linear correlation with the current functional state. However, this component remained significantly different from its normal shape and varied only in a narrow range. In patients with reversible unconsciousness, time course of changes in amplitude and latency between recovery stages was of linear character with a tendency to normalization. The findings suggest that, in reversible unconsciousness states, processing of sensory information at different recovery stages may be performed with various functional systems that determine varying quality of processing, whereas changes in chronic unconsciousness are caused by a decrease in the number of active elements within the same functional system. PMID- 17285771 TI - [Role of the parietal associative cortex in "counting" behavior of dogs]. AB - Influence of the combined and isolated lesions of areas 5 and 7 of the parietal cortex on the counting behavior was studied in experiments with 6 dogs. Instrumental feeding reaction (lifting and placing the forepaw on the foodwell) was established. The positive conditioned stimulus was a series of 5 clicks with variable interclicks intervals and the negative (non-reinforced) conditioned stimulus was a series of 3 clicks, so that asymmetrical differentiation was elaborated. Combined bilateral lesions of areas 5 and 7 and an isolated lesion of area 5 resulted in a severe impairment of the numerical discrimination for two months, whereas the isolated lesion of area 7 did not lead to any problems in differentiation. The conclusion was made that area 5 is critical for numerical discrimination of sequential stimuli. PMID- 17285772 TI - [Manifestation of active and passive defensive behavior in juvenile rats]. AB - The dynamics of freezing and flight reactions in juvenile rats was investigated. The rats were tested on the 20th, 25th, 35th, and 40th postnatal days. A sound of 6-sec duration (bell) was used as a threatening stimulus. The following parameters were recorded: number of rearing reactions and defecations within 5 min prior to stimulation, reactions to the bell, latent periods and durations of freezing reactions, freezing posture rigidity, and time of recovery of movements after freezing. It was shown that the intensity of freezing reduced in the period from the 20th to 35th postnatal day. The flight reactions were highest on the 25th and 40th days. Correlations between freezing indices and numbers of rearing and defecation reactions were different in rats of all age groups. The results suggest that the structure of defensive behavior changes with maturation of principal defensive reactions in rats within the first 40 postnatal days. PMID- 17285773 TI - [Effect of furosemide on changes in the rat behavior produced by intrastriatal GABA or picrotoxin microinjections]. AB - It was shown in chronic rat experiments that multiple microinjections of furosemide into the rostral region of the neostriatum facilitated avoidance conditioning in a shuttle box and prevented from GABA-induced deviant freezing, but did not abolish the choreic hyperkinesis produced by picrotoxine (GABA-A receptors antagonist) intrastriatal microinjections. Simultaneous microinjections of furosemide and picrotoxine into the neostriatum increased differences in parameters of picrotoxine-induced hyperkinesis between rat groups capable and incapable (extinct reflex) for conditioned avoidance. These findings point to a certain correlation between the intensity of hyperkinesis, capability for acquisition and realization of avoidance conditioning, and activity of neostriatal neurotransmitter systems involved in neuronal homeostasis. The findings suggest an involvement of neostriatal GABAergic system in conditioning and organization of free locomotor behavioral acts. PMID- 17285775 TI - [Electrophysiological characteristics of a population of mushroom body neurons in Apis mellifera L. honey bee under conditions of kynurenines deficit]. AB - Neurophysiological characteristics of mushroom body neurons were examined by electrophysiological methods in mutants snow(laranja) and wild-type honey bees. Mutation snow(laranja) causes a drastic decrease in the activity of enzyme tryptophane oxygenase that results in deficiency of all kynurenines. It also modifies bioelectrical properties of neurons in the mushroom bodies. The duration of afterdepolarization in spikes recorded from calyx neurons and the amplitude of postsynaptic potentials in these neurons evoked by focal stimulation of antennal lobes were shown to be most dependent on the mutation and, consequently, on the content of endogenous kynurenines. A tendency to an increase in the frequency of spontaneous spikes was also observed. The effect of the mutation on neurophysiological characteristics under study was recessive, i.e. it was observed only in homozygous individuals. PMID- 17285774 TI - [Epileptogenic activity of tripeptide corticotropin-releasing factor fragment (CRF(4-6))]. AB - The effects of centrally administered tripeptide fragment CRF(4-6) of corticotropin-releasing factor on convulsive activity in outbred albino rats were investigated. The peptide CRF(4-6) (icv; 6, 30, 150 nmol/head) causes dose dependent increase in total EEG power in 1-40 Hz frequency range as a reflection of tripeptide-induced various epileptiform EEG signs such as single peaks and spike trains without external convulsion. Higher doses of CRF(4-6) (icv; 150, 225, 300 nmol per animal) induce tonicoclonic seizures. Switching to convulsive activity occurs at CRF(4-6) dose of 150 nmol per animal: injection of this dose leads only to EEG paroxysmal activity under habitual conditions and induces pathological locomotor activation under stressing conditions. Thus, CRF(4-6) similarly to full-length corticotropin-releasing factor induces epileptiform activity in rats. PMID- 17285776 TI - [Immunohistochemical detection of transcription factors CREB and c-Fos activation in the land snail nervous system induced by pentylenetetrazole]. AB - Phosphorylation of transcription factor CREB and expression of immediate early gene c-fos play a key role in molecular mechanisms of long-term neuronal plasticity in the vertebrate brain. Here, we have defined the procedure of immunohistochemical detection of pCREB and c-Fos in the nervous system of the land snail Helix lucorum (Pulmonata: Stylommatophora) and have shown its activation after the convulsant pentylenetetrazole injection. Baseline pCREB1 and c-Fos levels in the intact snail nervous system appeared to be low. In contrast, injection of pentylenetetrazole (600 mg/kg) produced a rapid induction of CREB phosphorylation and c-Fos expression in a wide range of neurons including a number of identified cells. Double immunofluorescence for pCREB and c-Fos showed that c-Fos was always colocalized with pCREB-immunoreactivity, although the latter had a broader pattern. The results suggest that transcription factors CREB and c-Fos can be used as molecular markers for mapping long-term neuronal plasticity in molluscan nervous system. PMID- 17285777 TI - [Assessment of "impulsive" behavior by the method with time calculation]. AB - In this paper the problem of "impulsive" and "self-control" behaviour in animals and the experimental models for their assessment are discussed. It is pointed out that a widely accepted model for assessment of impulsive behaviour in animals predominantly measures their ongoing properties of impulsivity/self-control independently on belonging them to the certain types of higher nervous activity. In contrary, our model at the first instance assesses the typological characteristics of animals, including impulsivity and self-control, by their abilities to perform or not to perform an appropriate behaviour. The differences in the data obtained by these two different models and the possible reasons for it are discussed. PMID- 17285778 TI - Leopold Ruzicka--1939 Nobel Prize in chemistry. PMID- 17285779 TI - Colonic lipoma with intussusception. PMID- 17285780 TI - Testosterone replacement therapy: what we know is not yet enough. PMID- 17285781 TI - Lung cancer screening results: easily misunderstood. PMID- 17285782 TI - Testosterone use in men with sexual dysfunction: a systematic review and meta analysis of randomized placebo-controlled trials. AB - OBJECTIVE: To conduct a systematic review and meta-analysis of randomized placebo controlled trials to measure the effect of testosterone use on sexual function in men with sexual dysfunction and varying testosterone levels. METHODS: Librarian designed search strategies were used to search the MEDLINE (1966 to October 2004), EMBASE (1988 to October 2004), and Cochrane CENTRAL (inception to October 2004) databases. The MEDLINE search was rerun in March 2005. We also reviewed reference lists from included studies and content expert files. We selected randomized placebo-controlled trials of testosterone vs placebo that enrolled men with sexual dysfunction and measured satisfaction with erectile function and libido and overall sexual satisfaction. RESULTS: We included 17 trials (N = 862 participants) in this review. Trials that enrolled participants with low testosterone levels showed (1) a moderate nonsignificant and inconsistent effect of testosterone use on satisfaction with erectile function (random-effects pooled effect size, 0.80; 95% confidence interval [CI], -0.10 to 1.60), (2) a large effect on libido (pooled effect size, 1.31; 95% CI, 0.40 to 2.25), and (3) no significant effect on overall sexual satisfaction. Trials that enrolled patients with low-normal and normal testosterone levels at baseline showed testosterone that caused (1) a small effect on satisfaction with erectile function (pooled effect size, 0.34; 95% CI, 0.03 to 0.65), (2) moderate nonsignificant effect on libido (pooled effect size, 0.41; 95% CI, -0.01 to 0.83), and (3) no significant effect on overall sexual satisfaction. CONCLUSION: Testosterone use in men is associated with small improvements in satisfaction with erectile function and moderate improvements in libido. Unexplained inconsistent results across trials, wide CIs, and possible reporting bias weaken these inferences. PMID- 17285783 TI - Testosterone and cardiovascular risk in men: a systematic review and meta analysis of randomized placebo-controlled trials. AB - OBJECTIVE: To conduct a systematic review and meta-analysis of randomized trials that assessed the effect of testosterone use on cardiovascular events and risk factors in men with different degrees of androgen deficiency. METHODS: Librarian designed search strategies were used to search the MEDLINE (1966 to October 2004), EMBASE (1988 to October 2004), and Cochrane CENTRAL (inception to October 2004) databases. The database search was performed again in March 2005. We also reviewed reference lists from included studies and content expert files. Eligible studies were randomized trials that compared any formulation of commercially available testosterone with placebo and that assessed cardiovascular risk factors (lipid fractions, blood pressure, blood glucose), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, angina or claudication, revascularization, stroke), and cardiovascular surrogate end points (ie, laboratory tests indicative of cardiac or vascular disease). Using a standardized data extraction form, we collected data on participants, testosterone administration, and outcome measures. We assessed study quality with attention to allocation concealment, blinding, and loss to follow-up. RESULTS: The 30 trials included 1642 men, 808 of whom were treated with testosterone. Overall, the trials had limited reporting of methodological features that prevent biased results (only 6 trials reported allocation concealment), enrolled few patients, and were of brief duration (only 4 trials followed up patients for > 1 year). The median loss to follow-up across all 30 trials was 9%. Testosterone use in men with low testosterone levels led to inconsequential changes in blood pressure and glycemia and in all lipid fractions (total cholesterol: odds ratio [OR], -0.22; 95% confidence interval [CI], -0.71 to 0.27; high-density lipoprotein cholesterol: OR, -0.04; 95% CI, -0.39 to 0.30; low-density lipoprotein cholesterol: OR, 0.06; 95% CI, -0.30 to 0.42; and triglycerides: OR, -0.27; 95% CI, -0.61 to 0.08); results were similar in patients with low-normal to normal testosterone levels. The OR between testosterone use and any cardiovascular event pooled across trials that reported these events (n = 6) was 1.82 (95% CI, 0.78 to 4.23). Several trials failed to report data on measured outcomes. For reasons we could not explain statistically, the results were inconsistent across trials. CONCLUSION: Currently available evidence weakly supports the inference that testosterone use in men is not associated with important cardiovascular effects. Patients and clinicians need large randomized trials of men at risk for cardiovascular disease to better inform the safety of long-term testosterone use. PMID- 17285784 TI - Second-generation antiepileptic drugs' impact on balance: a meta-analysis. AB - OBJECTIVE: To systematically review available evidence regarding whether second generation antiepileptic drugs (AEDs) contribute to the risk of balance disorders. METHODS: We systematically evaluated data from randomized controlled trials that compared adjunctive therapy with a second-generation AED (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topIramate, or zonisamide) vs placebo for partial epilepsy and that reported dose-specific rates of ataxia or Imbalance for each group. Random-effects meta-analysis was used to pool ratios (risk ratio [RR]) and associated 95% confidence Intervals to determine whether there was evidence of an overall AED class effect or a dose response effect and whether there were differences between Individual AEDs. RESULTS: Sixteen studies met inclusion criteria, representing 4279 individuals randomized to a second-generation AED and 1830 patients to placebo. Pooled analyses of all AEDs demonstrated that they Increase imbalance risk at any dose (RR, 2.73; 95% confidence interval, 2.07-3.61) and at lowest dose (RR, 1.76; 95% confidence interval, 1.26-2.46). The highest dose analysis showed heterogeneity; evaluation of individual AEDs revealed that oxcarbamazepine and topiramate increased imbalance risk at all doses, whereas gabapentin and levetiracetam did not increase imbalance risk at any dose. A dose-response effect was observed for most AEDs. CONCLUSION: Second-generation AEDs at standard dosages, except for gabapentin and levetiracetam, increase the imbalance risk, and evidence exists for a dose-response effect. The mechanisms, risk factors, and consequences of this risk for individual AEDs warrant further study. PMID- 17285785 TI - Retrospective study of pulmonary function tests in patients presenting with isolated reduction in single-breath diffusion capacity: implications for the diagnosis of combined obstructive and restrictive lung disease. AB - OBJECTIVE: To examine the frequency and spectrum of diseases associated with isolated reduction in the diffusing capacity of lung for carbon monoxide (D(Lco)). PATIENTS AND METHODS: We retrospectively identified all potentially dyspneic patients who had pulmonary function tests (PFTs) performed at the Mayo Clinic in Jacksonville, Fla, between January 1, 1990, and June 30, 2000, that showed reduced D(Lco) (< 70% of predicted), normal lung volumes (total lung capacity and residual volume > 80% and < 120% of predicted, respectively), and airflow variables (forced expiratory volume in 1 second and forced vital capacity values > 80% of predicted and forced expiratory volume in 1 second/forced vital capacity ratio > 70% of predicted). Only patients who had also undergone chest computed tomography (CT) and echocardiography within 1 month of PFTs were studied. RESULTS: Of the 38,095 patients who underwent PFTs during the study period, 179 (0.47%; 95% confidence interval [CI], 0.40%-0.54%) had isolated D(Lco) abnormalities. The 27 patients (15.1%; 95% CI, 10.2%-21.2%) who had also undergone chest CT and echocardiography within 1 month of PFTs form the study cohort reported herein. Their mean D(Lco) was 50% +/- 15% (95% CI, 45%-56%) with average normal pulse oxygen saturation at rest and mild hypoxemia with activity. Thirteen of the 27 patients (48%; 95% CI, 28.7%-68.1%) had underlying emphysema evident on CT. Eleven of these 13 patients had emphysema associated with a restrictive lung process. The 14 patients without emphysema had interstitial lung disease, pulmonary vascular disease, and other isolated findings. Six patients with combined emphysema and idiopathic pulmonary fibrosis accounted for the largest percentage (22%) of patients with Isolated D(Lco) reduction. The mean +/- SD smoking history of the 27 patients in the study cohort was 36 +/- 33 pack years (range, 0-116 pack-years). CONCLUSION: Dyspneic patients with respiratory symptoms and normal lung volumes and airflows associated with Isolated reduction in D(Lco) should be evaluated for underlying diseases such as emphysema, with or without a concomitant restrictive process, and pulmonary vascular disease. PMID- 17285786 TI - Chronic cough from the patient's perspective. AB - OBJECTIVE: To identify the factors that patients consider most concerning about their cough. PATIENTS AND METHODS: All consecutive patients who presented with a complaint of chronic cough between November 1, 2000, and February 28, 2001, were prospectively surveyed for cough-related complaints using an 18-item symptom complaint questionnaire. We analyzed frequencies of responses and response patterns to specific items on the questionnaire. We also examined whether the responses to individual items related to the patient's age, sex, and duration of cough. RESULTS: Of the 146 consecutive patients referred for evaluation of chronic cough, 136 were eligible for inclusion in the study. These patients cited feelings of frustration, irritability, or anger (43%), frequent physician visits and testing (41%), and sleep disturbances (38%) as the most prevalent major problems. The responses to individual items on the questionnaire were not related to patients' age, sex, and cough duration. Anxiety about underlying serious illness continued to be a concern for most patients. CONCLUSIONS: Frustration, anger, or anxiety was the most frequent major problem cited by patients. Frequent physician visits and testing was the unexpected second most frequent major problem. These findings are important because most chronic cough guidelines are based on clinical efficacy and cost-effectiveness considerations rather than on patient satisfaction. Future studies regarding chronic cough evaluation should take into account patient satisfaction and perceived burden of disease as outcome variables. PMID- 17285787 TI - Twelve-month tolerability and safety of sumatriptan-naproxen sodium for the treatment of acute migraine. AB - OBJECTIVES: To evaluate the long-term safety and tolerability of sumatriptan naproxen sodium for the treatment of moderate to severe acute migraines and to assess the safety of administration of an optional second dose. PATIENTS AND METHODS: A 12-month, multicenter, open-label safety study was conducted in adults treated for migraine attacks of moderate to severe intensity from April 14, 2004, to August 18, 2005. Safety evaluations included adverse events and laboratory tests. RESULTS: Of 600 patients enrolled, 565 (94%) were treated for at least 1 migraine. Of treated patients, 414 (73%) and 362 (64%) completed 6 and 12 months of treatment, respectively. Of the 24,485 attacks treated, 17,144 (70%) were treated with only 1 dose. On average, patients treated 5 migraine attacks per month, with a median of 6 days between attacks. The most common treatment-related adverse events were nausea, muscle tightness, and dizziness. Fourteen patients reported 1 or more serious adverse event with only 1 judged probably related to treatment. No deaths occurred. Eight percent of patients discontinued participation in the study because of adverse events or pregnancy. The rates of adverse events reported were no higher after treatment with 2 tablets (at least 2 hours apart) compared with 1 tablet. CONCLUSIONS: In this 12-month data set of more than 24,000 migraine attacks in 565 patients, sumatriptan-naproxen sodium formulated in a single tablet was well tolerated when used episodically for the treatment of acute migraine. The adverse events did not differ from those expected for the individual components alone, and no new or unexpected findings occurred. PMID- 17285788 TI - Homeopathy for childhood and adolescence ailments: systematic review of randomized clinical trials. AB - OBJECTIVE: To assess the evidence of any type of therapeutic or preventive intervention testing homeopathy for childhood and adolescence ailments. METHODS: Systematic literature searches were conducted through January 2006 in MEDLINE, EMBASE, AMED, CINAHL, Cochrane Central, British Homeopathic Library, ClinicalTrials.gov, and the UK National Research Register. Bibliographies were checked for further relevant publications. Studies were selected according to predefined inclusion and exclusion criteria. All double-blind, placebo-controlled randomized clinical trials of any homeopathic intervention for preventing or treating childhood and adolescence ailments were included. According to the classification of the World Health Organization, the age range defined for inclusion was 0 to 19 years. Study selection, data extraction, and assessment of methodological quality were performed independently by 2 reviewers. RESULTS: A total of 326 articles were identified, 91 of which were retrieved for detailed evaluation. Sixteen trials that assessed 9 different conditions were included in the study. With the exception of attention-deficit/hyperactivity disorder and acute childhood diarrhea (each tested in 3 trials), no condition was assessed in more than 2 double-blind randomized clinical trials. The evidence for attention deficit/hyperactivity disorder and acute childhood diarrhea is mixed, showing both positive and negative results for their respective main outcome measures. For adenoid vegetation, asthma, and upper respiratory tract infection each, 2 trials are available that suggest no difference compared with placebo. For 4 conditions, only single trials are available. CONCLUSION: The evidence from rigorous clinical trials of any type of therapeutic or preventive intervention testing homeopathy for childhood and adolescence ailments is not convincing enough for recommendations in any condition. PMID- 17285790 TI - Treatment of obesity. AB - For primary care physicians, obesity is one of the most challenging problems confronted in office practice. The disorder is Increasing in prevalence despite the efforts of both patients and physicians. Treatment requires a multimodality approach that addresses diet, physical activity, and behavioral issues. Medication and surgical approaches may be appropriate as well. This review outlines the evidence for each approach, suggests how primary care physicians can best help obese patients, and provides practical tips for weight loss. PMID- 17285789 TI - Treatment of warfarin-associated intracerebral hemorrhage: literature review and expert opinion. AB - Wider use of oral anticoagulants has led to an increasing frequency of warfarin related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent decades. In contrast to spontaneous ICH, the duration of bleeding is 12 to 24 hours in many patients, offering a longer opportunity for intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor VIIa only (2 experts) to recombinant factor VIIa along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence. PMID- 17285791 TI - 33-year-old woman with marked eosinophilia. PMID- 17285792 TI - Cancer symposium for the practitioner: introduction to solid tumors. PMID- 17285793 TI - Colorectal cancer. AB - Cancers of the colon and rectum will affect 1 in 17 North Americans during their lifetime. The progress witnessed in the treatment of these cancers in recent years has been remarkable. Improvements have been realized in surgical technique, radiation therapy, and systemic therapies, particularly with the addition of oxaliplatin and irinotecan to the previously limited armamentarium of fluorouracil alone. Targeted therapies directed at the vascular endothelial growth factor pathway and the epidermal growth factor pathway are now key players in the treatment of colorectal cancer. With current-day therapies, more than 75% of patients with localized disease are recurrence free at 3 years, and up to 50% of patients with advanced unresectable disease are alive at 2 years. This review focuses on the evidence supporting the current role of chemotherapy and radiation therapy in the adjuvant management of colorectal cancers and the strategy of combining chemotherapy and biological therapy in the treatment of metastatic disease. PMID- 17285794 TI - Usefulness of acupuncture and hypnosis for anesthesia. PMID- 17285795 TI - A potential anatomic cause of mandibular osteonecrosis in patients receiving bisphosphonate treatment. PMID- 17285796 TI - Recurrent streptococcal pharyngitis. PMID- 17285797 TI - Non-enzymatic glycation of proteins: a cause for complications in diabetes. AB - Diabetes mellitus is one of the most common non-communicable diseases, and is the fifth leading cause of death in most of the developed countries. It can affect nearly every organ and system in the body and may result in blindness, end stage renal disease, lower extremity amputation and increase risk of stroke, ischaemic heart diseases and peripheral vascular disease. Hyperglycemia in diabetes causes non-enzymatic glycation of free amino groups of proteins (of lysine residues) and leads to their structural and functional changes, resulting in complications of the diabetes. Glycation of proteins starts with formation of Shiff's base, followed by intermolecular rearrangement and conversion into Amadori products. When large amounts of Amadori products are formed, they undergo cross linkage to form a heterogeneous group of protein-bound moieties, termed as advanced glycated end products (AGEs). Rate of these reactions are quite slow and only proteins with large amounts of lysine residues undergo glycation with significant amounts of AGEs. The formation of AGEs is a irreversible process, causing structural and functional changes in protein leading to various complications in diabetes like nephropathy, retinopathy, neuropathy and angiopathy. The present review discusses about role of glycation in various complications of diabetes. PMID- 17285798 TI - Overexpression of a recombinant gamma-glutamyltranspeptidase from Escherichia coli Novablue. AB - A truncated Escherichia coli Novablue gamma-glutamyltranspeptidase (EcGGT) gene, lacking the first 48-bp coding sequence for part of the signal sequence, was amplified by polymerase chain reaction (PCR) and cloned into expression vector pQE-30 to generate pQE-EcGGT. The maximum production of His6-tagged enzyme by E. coli M15 (pQE-EcGGT) was achieved with 0.1 mM IPTG induction for 12 h at 20 degrees C. The overexpressed enzyme was purified to homogeneity by nickel-chelate chromatography to a specific transpeptidase activity of 4.25 U/mg protein and a final yield of 83%. The molecular masses of the subunits of the purified enzyme were determined to be 41 and 21 kDa respectively by SDS-PAGE, indicating the precursor EcGGT still undergoes the post-translational processing even in the truncation of signal sequence. His6-tagged EcGGT migrated relative to the molecular mass of approximately 120 kDa and its heterodimeric structure was confirmed by a native-PAGE gel. PMID- 17285799 TI - Mechanism of inhibition of Ca2+-transport activity of sarcoplasmic reticulum Ca2+ ATPase by anisodamine. AB - The mechanism of inhibition of Ca2+-transport activity of rabbit sarcoplasmic reticulum Ca 2+-ATPase (SERCA) by anisodamine (a drug isolated from a medicinal herb Hyoscyamuns niger L) was investigated by using ANS (1-anilino-8 naphthalenesulfonate) fluorescence probe, intrinsic fluorescence quenching and Ca 2+-transport activity assays. The number of ANS binding sites for apo Ca2+-ATPase was determined as 8, using a multiple-identical binding site model. Both anisodamine and Ca2+ at millimolar level enhanced the ANS binding fluorescence intensities. Only anisodamine increased the number of ANS molecules bound by SERCA from 8 to 14. The dissociation constants of ANS to the enzyme without any ligand, with 30 mM anisodamine and with 15 mM Ca 2 were found to be 53.0 microM, 85.0 microM and 50.1 microM, respectively. Both anisodamine and Ca2+ enhanced the ANS binding fluorescenc with apparent dissociation constants of 7.6 mM and 2.3 mM, respectively, at a constant concentration of the enzyme. Binding of anisodamine significantly decreased the binding capacity of Ca2+ with the dissociation constant of 9.5 mM, but binding of Ca2+ had no obvious effect on binding of anisodamine. Intrinsic fluorescence quenching and Ca2+-transport activity assays gave the dissociation constants of anisodamine to SERCA as 9.7 and 5.4 mM, respectively, which were consistent with those obtained from ANS binding fluorescence changes during titration of SERCA with anisodamine and anisodamine + 15 mM Ca2+, respectively. The results suggest that anisodamine regulates Ca2+-transport activity of the enzyme, by stabilizing the trans membrane domain in an expanded, inactive conformation, at least at its annular ring region. PMID- 17285800 TI - 3D-QSAR of histone deacetylase inhibitors as anticancer agents by genetic function approximation. AB - Histone deacetylases (HDACs) play a critical role in gene transcription and are implicated in cancer therapy and other diseases. Inhibitors of HDACs induce cell differentiation and suppress cell proliferation in the tumor cells. Although many such inhibitors have been designed and synthesized, but selective inhibitors for HDAC isoforms are lacking. Various hydroxamic acid analogues have been reported as HDAC inhibitors. Here, we report a three-dimensional quantitative structure activity relationship (3D-QSAR) study performed using genetic function approximation (GFA) for this class of molecules. QSAR models were generated using a training set of 39 molecules and the predictive ability of final model was assessed using a test set of 17 molecules. The internal consistency of the final QSAR model was 0.712 and showed good external predictivity of 0.585. The results of the present QSAR study indicated that molecular shape analysis (MSA). thermodynamic and structural descriptors are important for inhibition of HDACs. PMID- 17285801 TI - A new fragmentation rearrangement of the N-terminal protected amino acids using ESI-MS/MS. AB - A novel fragmentation rearrangement reaction with a carboxyl oxygen negative charge migration was observed in the N-terminal protected amino acids including Fmoc-protected phosphoserine. phosphothroenine, and phosphotyrosine and their analogues using the electrospray ionization tandem mass spectrometry (ESI-MS/MS). The possible mechanism of a five-membered ring transition state was proposed and supported by the further experiments. It was found that the tendency of the rearrangement was determined by the blocking status of its C-terminal and the reaction was proved to be independent of the N-terminal and side-chain protecting groups of the amino acids. PMID- 17285802 TI - Biosynthesis of protease from Lactobacillus paracasei: kinetic analysis of fermentation parameters. AB - Fifteen strains of Lactobacillus species, isolated from different samples of curd were screened for their ability to produce more extracellular protease. The proteolytic activities of these strains based on casein hydrolysis showed a variation of 1.26-5.80 U ml(-l), with Lactobacillus IH8 showing the maximum activity and was identified as L. paracasei. Different cultural conditions for enhanced production of protease by L. paracasei were optimized. The optimal conditions for production of the enzyme were an incubation temperature of 35 degrees C and a medium pH of 6.0. The maximum proteolytic activity of L. paracasei (7.28 Uml(-1)) was achieved after 48 h of cultivation. The kinetic parameters such as product yield (Yp/x,), growth yield (Yx/s), specific product yield (qp) and specific growth yield (qs) coefficients also revealed that the values of experimental results were kinetically significant. PMID- 17285803 TI - Facultative alkalophilic bacteria from mangrove soil with varying buffering capacity and H+ conductance. AB - Facultative alkalophilic bacteria Planococcus sp. (EMGA-26), Bacillus sp. (EMGA 29) and Corynebacterium spp. (EMGA-33 and 130) were isolated from mangrove soil samples. Neutrophiles were predominant than alkalophiles. Buffering capacity and membrane H+ conductance were investigated for the strains grown in PPYG medium at pH 10.5 using acid pulse technique. Bacillus sp. showed higher buffering capacity than Planococcus sp. and Corynebacterium spp. Buffering capacity was two-fold higher in Corynebacterium sp. EMGA-33 than in EMGA-130. The membrane H+ conductance was high in Bacillus sp. and was directly proportional to the buffering capacity values. The Bacillus sp. (EMGA-29) had higher cell membrane adaptability in high pH environment than the Planococcus sp. and Corynebacterium spp. PMID- 17285804 TI - Acute effects of a partially purified fraction from garlic on plasma glucose and cholesterol levels in rats: putative involvement of nitric oxide. AB - Garlic has been extensively used as a medicinal plant. Most of its numerous beneficial effects such as antioxidant, antibacterial, antitumoral involve sulfur derived amino acids. In the present work, we reevaluated the acute effects of aqueous extract of garlic on plasma glucose and cholesterol levels in normal rats. Control (vehicle H2O) or garlic extract-treated group at 100-120 mg protein/kg body wt were intraperitoneally injected (IP) and glucose, cholesterol, insulin and nitric oxide metabolites levels were determined after a short-term duration of 6 h. We confirmed that garlic contained an active fraction, exerting both glucose and cholesterol-lowering activity. The glucose-lowering effect was triggered by an increase in insulinemia. Preliminary study indicated that the active agent was different from S-allyl-cysteine-sulfoxide, the active principle implicated in hypoglycaemic and hypolipidemic effects of garlic or arginine. The mechanism of action seemed to involve nitric oxide (NO), which increased time and dose-dependently. The garlic effects were abolished by diphenyleneiodonium chloride (DPI = 1 mg/kg body wt), a specific inhibitor of NO production, suggesting the involvement of constitutive nitric oxide synthase. PMID- 17285805 TI - Purification of L-asparaginase from a bacteria Erwinia carotovora and effect of a dihydropyrimidine derivative on some of its kinetic parameters. AB - L-Asparaginase shows antileukemic activity and is generally administered in the body in combination with other anticancer drugs like pyrimidine derivatives. In the present study, L-asparaginase was purified from a bacteria Erwinia carotovora and the effect of a dihydropyrimidine derivative (1-amino-6-methyl-4-phenyl-2 thioxo, 1,2,3,4-tetrahydropyrimidine-5-carboxylic acid methyl ester) was studied on the kinetic parameters Km and Vmax of the enzyme using L-asparagine as substrate. The enzyme had optimum activity at pH 8.6 and temperature 35 degrees C, both in the absence and presence of pyrimidine derivative and substrate saturation concentration at 6 mg/ml. For the enzymatic reaction in the absence and presence (1 to 3 mg/ml) of dihydropyrimidine derivative, Km values were 7.14, 5.26, 4.0, and 5.22 M, and Vmax values were 0.05, 0.035, 0.027 and 0.021 mg/ml/min, respectively. The kinetic values suggested that activity of enzyme was enhanced in the presence of dihydropyrimidine derivative. PMID- 17285806 TI - Debate over biologics heats up in Congress. PMID- 17285807 TI - Employers want plans & PBMs to push hard for generics. PMID- 17285808 TI - Change from salary to relative value units leads to higher income for physicians. PMID- 17285809 TI - Erosion of employer-sponsored health care. Bad for everyone. PMID- 17285810 TI - Will 'mea culpa' work for health plans too? PMID- 17285811 TI - Rise of the PHR. PMID- 17285812 TI - Employers publish guide on prevention's worth. PMID- 17285813 TI - The use of therapeutic interchange for biologic therapies. AB - Therapeutic interchange is the practice of switching or dispensing drugs that are chemically distinct but therapeutically similar in terms of their efficacy, safety, and tolerability profiles. The stated goal of therapeutic interchange is to achieve an improved or neutral outcome with the new agent while reducing overall treatment costs. Until recently, most interchange programs have been limited to switches within drug classes, such as angiotensin-converting enzyme (ACE) inhibitors, proton pump inhibitors (PPIs), HMG-CoA reductase inhibitors (statins), and selective serotonin reuptake inhibitors (SSRIs), and generally to drugs that use the same routes of administration. Therapeutic interchange now is being applied to some biologic agents, such as those used to treat psoriasis and rheumatoid arthritis (RA). In some cases, these agents differ in structure and mode of administration. Patients who require a biologic agent are often difficult to manage, and the comorbidities that are prevalent in these patients further complicate management and agent selection. Population-based outcomes among various agents may not appear notably different, but because there is no a priori means to determine the effects of a given biologic agent on any individual patient, therapeutic interchange is inadvisable once a patient receiving RA or psoriasis therapy has been stabilized. However, if a biologic agent has been designated as preferred on a formulary, it is reasonable to initiate treatment with that agent in a patient who is naive to biologic therapy if that agent is not contraindicated. Respectful, two-way communication between health care professionals and managed care organizations (MCOs) will help ensure that a patient receives the appropriate therapy at the right time. PMID- 17285814 TI - New coagulant bypasses clotting dysfunction in hemophilia. PMID- 17285815 TI - 2007 forecast. Revenue grows but membership declines. PMID- 17285816 TI - Mechanisms of electrode induced injury. Part 1: theory. AB - Electrodes are the essential elements of clinical neurophysiology both in recording of neural activity and in functional electrical stimulation of the nervous system. Therefore it is important to understand the potential complications of using electrodes. In this paper, the factors that influence the chance of electrode related injury are discussed from a theoretical standpoint. The mechanical factors, especially pressure related injury, are discussed first, followed by a discussion of injury that is of chemical origin such as contact dermatitis. Next, the ways in which electrical currents flowing from electrodes can cause injury including: Joule heating, electroporation, electroconformational denaturation, and excitatory neurotoxicity are discussed. The differential effects of constant current and constant voltage stimulation on tissue heating are examined, as are the effects of the conductivity and geometric structure of the stimulated tissue. Finally, the effects of electrochemical reactions are discussed both in the context of surface and implanted electrodes. PMID- 17285817 TI - Sleep/sedation in children undergoing EEG testing: a comparison of chloral hydrate and music therapy. AB - This study included a total of 60 pediatric patients ranging from 1 month through 5 years of age. The effects of chloral hydrate and music therapy were evaluated and compared as means of safe and effective ways to achieve sleep/sedation in infants and toddlers undergoing EEG testing. The results of the study indicate that music therapy may be a cost-effective, risk-free alternative to pharmacological sedation. PMID- 17285818 TI - Clinical significance of photic stimulation during routine EEGs of adult patients. AB - Intermittent photic stimulation (IPS) is an activating procedure meant to elicit or accentuate epileptiform discharges during an EEG. There is insufficient clinical data to advocate IPS in the routine EEGs of all adult patients. We therefore sought to address the clinical significance of routine IPS in the adult population. We retrospectively reviewed 100 consecutive abnormal EEGs in adult patients (inpatients and outpatients) who had undergone photic stimulation in our laboratory. Nine patients had abnormalities noted during IPS. The abnormalities consisted of sharp waves in four patients and focal slowing in five patients. Only one patient had abnormalities on IPS that provided information additional to that seen on the baseline record. PMID- 17285819 TI - Subdermal needle electrodes: an option for emergency ("stat") EEGs. AB - Emergency or "stat" EEGs are ordered on patients who are suspected to have serious acute brain dysfunction (ABD). Often, these patients are comatose or have some altered level of consciousness (ALOC) from stroke, brain hemorrhage, head trauma, encephalopathy, seizures, or status epilepticus--which may be convulsive (SE) or non-convulsive (NCSE). As the number of stat EEGs increases, consider alternatives to traditional methods and tools, keeping overall patient care and outcome in mind. PMID- 17285820 TI - Letter to the editor: Waveform Window #4--evoked potential examples. PMID- 17285821 TI - Waveform Window #6. Electrocorticography using subdural grid electrodes. PMID- 17285822 TI - Quality of work life in nursing: some issues and challenges. PMID- 17285823 TI - Issues in safety and quality in health care. PMID- 17285824 TI - Documentation of medication management by graduate nurses in patient progress notes: a way forward for patient safety. AB - Nursing documentation provides evidence of nurses' management, the patient response, and evaluation of care. The aim of the study was to examine how graduate nurses document their medication management in the progress notes. A prospective clinical audit of patient medication charts and the progress notes made by 12 graduate nurses was undertaken. Graduate nurses were also individually interviewed and asked clarifying questions about their medication management. Documentation was examined based on four areas: assessment, planning care, administration of medications, and evaluating outcomes of medications. Recorded information about assessment focused on cues of a biomedical rather than a psychosocial nature. Planning care involved non-specific documentation of discharge planning needs, and little information about communication with doctors, pharmacists, nurses, patients and next of kin. Administration of medications included details about the names of medications given to patients, but no information about medication education provided to patients during this time. Evaluation of outcomes of medication administration was poorly documented. Graduate nurses tended to focus on assessing medications before their administration without considering how the patient responded to treatment. Recommendations are proposed for improving the quality of graduate nurses' progress notes. These recommendations include implementing and evaluating protocols that link nurses' decision-making to documentation processes. Adopting a supportive multidisciplinary approach to quality improvement and providing education that emphasises written documentation of verbal communication are also recommended. PMID- 17285825 TI - Evidence-based management in clinical governance. AB - The aim of this paper is to describe a strategy--a partnership between a clinician manager and nurse academic--developed for the purpose of utilizing clinical governance literature to enhance management practice. The partnership is an initiative that has been implemented to fill a growing need for more collaboration between the tertiary health education and health industry sectors. The paper provides a brief overview of clinical governance and evidence-based management, and describes the partnership between the clinician manager and nurse academic. For the purposes of this paper 'clinician manager' refers to a health professional who also has an extensive management role in a health care organization. The benefits of this partnership in terms of the application of clinical governance literature to improved management decision making and practice concern the ability of clinician managers to have access to the most up to-date research findings in terms of good clinical governance, and to be able to apply them in their management practice. Information about clinical governance, linked with evidence-based management and the application of clinical governance literature in the management of a health service is also provided. The authors argue that this is a useful initiative which could be adopted by health care managers and academics--with the aim of enhancing evidence-based management policy and decision making. PMID- 17285826 TI - Being strategic: utilising consumer views to better promote an expanded role for nurses in Australian general practice. AB - Australian consumers have articulated their perceptions of the role of the nurse in general practice. Practice Nurses (PNs) and General Practitioners (GPs) have also highlighted the issues they believe currently and potentially impact on this role in Australia. This paper identifies and discusses the nexus between the consumers' perceptions and expectations and health professionals' issues. Data collected from focus groups and interviews in 2 Australian studies of consumer perception of nursing in general practice, are re-considered alongside findings reported in the Royal Australian College of General Practitioners and the Royal College of Nursing, Australia report; General Practice Nursing in Australia. Consumers, doctors and nurses working in general practices in Australia, raised similar issues. However, consumers considered these issues in relation to their health care needs, whereas the GPs and PNs tended to focus more on professional and structural tensions related to the current and potentially expanded role of the PN. Understanding consumer views vis-a-vis issues raised by PNs and GPs about the role of nursing in general practice provides direction for both professions to better work with consumers to enhance their understanding of what general practice services could be and how changes, like expanding the role of nurses, may bring about improvements in the health outcomes of consumers. Health professionals can benefit from reflecting on the experiences and expectations of consumers if they desire to make general practice services more responsive to individual consumer's needs and at the same time adopt a primary health care focus. PMID- 17285827 TI - The role of child health nurses in enhancing mothering know-how. AB - Supporting early parenting and promoting family health is an important aspect of contemporary child health nursing in Australia. Recent studies suggest that within a service climate that increasingly funds targeted, population-based needs rather than universal needs, child health nurses are concerned about maintaining individual nurse-client relationships, particularly with individual families. There is however, limited evidence available to use in response to these concerns. In this paper the way a group of middle-class mothers of infants, who, in today's health service climate, may not be a target group for health services, develop their caregiving know-how, is discussed. The findings presented suggest that both expert and lay knowledge have a part to play in supporting women in their early mothering. Women such as these, in essence, need a clearing-house to help them sift through the overwhelming information they access, respond to, and turn into everyday practices that work. Well placed child health nursing services may achieve this. While there is significant support for this claim in the literature, mechanisms for effective support remains the challenge. A key may be found in nurses focusing on the promotion of communicative or interactive health literacy as an outcome of their programs. PMID- 17285829 TI - New perspectives on old debates: re-engineering the theory practice gap. PMID- 17285828 TI - Community mental health nurses speak out: the critical relationship between emotional wellbeing and satisfying professional practice. AB - The article reports on selected findings of a research study concerning emotional wellbeing and professional nursing practice (Rose 2002). It highlights the relationship between community mental health nurses' and emotional wellbeing, and their capacity to provide satisfying professional nursing practice (Rose 2002). The notion of emotional wellbeing, factors that impacted upon the participants' emotional wellbeing, and the relationship of emotional wellbeing to professional practice were revealed in the study. These findings were based on a qualitative critical feminist research inquiry and specifically, interviews with five women community mental health nurses in Australia. Whilst complex, emotional wellbeing was found to be both implicitly and explicitly linked to the participants intertwined personal and professional experiences. Four key components were identified: the nebulous notion; the stress relationship; the mind, body, spirit connection; and, inner sense of balance. In terms of emotional wellbeing and professional practice, three themes were revealed. These were: being able to speak out (or not); being autonomous (or not) and being satisfied (or not). The authors argue that the emotional wellbeing of nurses working in community mental health settings is critical to satisfying professional practice. Furthermore nursing work involves emotional work which impacts on one's emotional wellbeing and emotional wellbeing is integrally linked to professional practice. It is recommended that health organisations must be pro-active in addressing the emotional needs of nurses to ensure the delivery of health care that is aligned to professional practice. This approach will ensure nurses will feel more recognised and validated in terms of their nursing practice. PMID- 17285830 TI - Competence in providing mental health care: a grounded theory analysis of nurses' experiences. AB - OBJECTIVE: In view of the evidence that general nurses have difficulty in caring for patients experiencing mental health problems, the aim of this study was to explore and describe the subjective experience of nurses in providing care for this client group. DESIGN: A grounded theory approach was used. The data were collected via semi-structured individual interviews and analysed using the constant comparative method. SETTING: The study was conducted with nurses from general health care settings that provide medical and surgical care and treatment. SUBJECTS: Four nurses who were completing their second year post graduation participated in the study. MAIN OUTCOME MEASURE: The experiences of providing care for people experiencing a mental illness as described by participants. RESULTS: The findings indicated the nurses were striving for competence in the provision of mental health care. They acknowledged the mental health needs of patients and their right to quality care. CONCLUSIONS: This study supports the notion that general nurses lack confidence when caring for patients with mental health problems in medical and surgical settings. It also highlights a discrepancy between the holistic framework encouraged at undergraduate level and what is experienced in practice. PMID- 17285831 TI - Stakeholders' views in relation to curriculum development approaches for Australian clinical educators. AB - OBJECTIVE: Clinical educators in nursing perform a crucial role in facilitating effective learning for students of nursing. They have the potential to act as a catalysing agent for learning--motivating students to make links between theory and practice, moving students safely from the known to the unknown, developing clinical skills and reflective practice. Whilst their role is extremely important, clinical educators in Australia are undervalued and under-supported. They are isolated and fragmented, and lack a unifying professional body and infrastructure to assist them in education, research and practice development. This paper reports on a study to explore what educational solutions could help to resolve the problem. DESIGN: A qualitative design utilising snowball sampling and semi-structured interviews was conducted. SETTING: The study took place in Queensland and thus results are limited to the needs identified in this region of Australia. SUBJECTS: Ten participants provided their views about educational innovations. CONCLUSIONS: There is strong support for a curriculum focused on clinical education and centred on the concept of a learning community in order to provide community and build capacity in the specialty group so that they become self-reliant and their achievements and contributions are sustainable. PMID- 17285832 TI - Dying for attention: palliative care in the acute setting. AB - BACKGROUND: Palliative care has emerged as a specialist discipline in the past 25 years. However in relation to acute hospitals, a sense exists that patients who are receiving end of life care may not experience support which fully reflects appropriate palliative care management. OBJECTIVE: This study aimed to analyse the end of life care received by patients in the acute wards of a busy teaching hospital. DESIGN: Retrospective analysis using multiple methods including: case note auditing and interviews of key staff was used to determine the quality of end of life support provided to an opportunistic sample of patients who died in acute care wards. SETTING: The research site is a 250 bed teaching hospital in South Australia. SUBJECTS: A medical record audit using an opportunistic sample of 20 recently deceased patients from acute wards was used. For each patient, interviews were also conducted with two nurses (n = 40) selected on the basis of having a major care involvement. MAIN OUTCOME: A range of strategies for enhancing the end of life care for patients in acute wards were determined, including support for application of a Palliative Care Advanced Disease Pathway. RESULTS: The lack of appropriate assessment and documentation indicates that major opportunities for enhanced service provision exist both in relation to physical care and even more significantly in relation to psychosocial and spiritual care. CONCLUSIONS: The end of life care provided for patients reviewed in this study indicates a far from ideal situation in the acute hospital wards of the research setting. An eagerness from the nurse participants in the study for tools and further support in their practice was noted and augurs well for future developments within the research site. PMID- 17285833 TI - Where do all the undergraduate and new graduate nurses go and why? A search for empirical research evidence. AB - OBJECTIVE: To review the published scientific literature for studies quantifying or examining factors associated with the attrition of undergraduate nursing students in pre-registration programs and the retention of graduate nurses in the workforce. METHODS: The following selection criteria were used to systematically search the literature: target populations were either students in pre registration nursing programs or registered nurses in their graduate year; the studies were to be primary observational or analytical (cross-sectional, case control or prospective cohort studies) in design; and outcome measures were attrition in undergraduate programs and/or retention of graduates within the workforce. Three authors guided by a standardised procedure performed data extraction and quality assessment independently. Synthesis of the data appears in text and tabular format. Due to the heterogenic nature of the study methods, meta analysis was not possible. RESULTS: This review found only four studies that met all inclusion criteria. All four studies examined undergraduate attrition as an outcome with two studies reporting a range of 25-27% attrition within the first year. No studies were found that quantified or examined retention of new graduates as an outcome measure. Only two of the four studies followed cohorts of students prospectively and were able to provide a high level of evidence, although each of these studies was designed to assess specific exposures as potential predictors of attrition, rather than assess actual factors associated with students leaving their program. CONCLUSION: There is a paucity of research studies in the literature from which evidence quantifying attrition and retention and the reasons why students leave undergraduate nursing programs or new graduates leave the profession can be obtained. Clearly there is a need to systematically track undergraduates and new graduates to quantify and understand attrition, retention and workforce choices within the nursing profession and begin to build this evidence-base. PMID- 17285834 TI - Tobacco smoking habits among a cross-section of rural Japanese nurses. AB - BACKGROUND: Despite a high community smoking rate, few investigations of tobacco usage among Japanese nurses have been conducted in rural areas, particularly those in the southern islands. AIM: The aim of this research was to investigate the epidemiology of tobacco smoking among a previously understudied group of rural Japanese nurses. DESIGN: A self-reporting questionnaire was adapted from previous investigations and distributed to a complete cross-section of 1162 nurses from a large teaching hospital in southern Japan (response rate: 74.0%). RESULTS: A total of 10.9% (95% Confidence Interval: 9.0-13.2) were current smokers, with a further 2.9% (95% CI: 2.0-4.3) being ex-smokers. When stratified by gender, the prevalence of smoking was 10.8% (95% CI: 8.9-13.1) among females, and 18.7% (95% CI: 6.6-43.0) among males. The median number was 10.0 cigarettes per day for a period of 10.0 years. When stratified by age, the highest smoking prevalence (16.4%) was observed among nurses aged between 45 and 50 years. In relation to career length, the highest smoking prevalence (13.3%) was demonstrated among those who had worked between 6 and 10 years. CONCLUSIONS: Overall, our study suggests that around 11% of rural nurses in southern Japan currently smoke tobacco. When stratified by gender however, the prevalence among male nurses was almost double that of their female counterparts. Although interventions to reduce smoking are clearly needed in this region, interventions will need to consider the underlying social and cultural motivations for tobacco usage among Japanese people, in general. PMID- 17285835 TI - Recognising and reconciling differences: mental health nurses and nursing students' perceptions of the preceptorship relationship. AB - OBJECTIVE: The main purpose of this study was to examine the preceptorship relationship between students' and mental health nurses' in the mental health setting. DESIGN: This study used a qualitative research design: grounded theory. This type of research method was deemed appropriate due to the limited knowledge of preceptorship in mental health. SETTING: One metropolitan area mental health service (AMHS) in Melbourne, Victoria, Australia agreed to participate in this study. The range of settings included adult acute, rehabilitation and community. SUBJECTS: Twenty 2nd year undergraduates nursing students from one metropolitan university in Melbourne, Australia agreed to participate in the study. In addition, nine mental health nurses from the nominated AMHS also consented to be involved. MAIN OUTCOME: The development of a substantive theory to describe the preceptorship relationship as informed by the study participants, student nurses and mental health nurses. For the purposes of this paper the category of 'reconciling difference' is the focus. RESULTS: The core category identified for mental health nurses was 'attempting to accomplish connectedness' and for the students, 'coping with uncertainty'. There were also many sub-categories, one of which was identified by both groups. This category is the main focus of this paper; reconciling difference. CONCLUSION: Dealing with the uncertainty of, and reconciling differences between, the general and mental health environments emerged as a strong theme from the research. Student nurses were faced with confronting situations within the environment and made various suggestions for improvement so that their learning could be enhanced rather than inhibited. These findings make an important contribution to the specific issues concerning preceptorship in the mental health environment. PMID- 17285836 TI - Utilization of King's interacting systems framework and theory of goal attainment with new multidisciplinary model: clinical pathway. AB - BACKGROUND: The critical role of research in nursing practice is the application of nursing theories to discover new knowledge. This study uses King's interacting systems framework and theory of goal attainment to investigate the effectiveness of implementing clinical pathways for patients undergoing transurethral resection of prostate (TURP) at Aga Khan University Hospital (AKUH), Pakistan. OBJECTIVE: To assess the impact of the implementation of a clinical pathway for the surgical procedure of TURP on clinical quality, cost, and patient and staff satisfaction. STUDY DESIGN: Quasi-experimental, non-equivalent control group study design using clinical pathway intervention. SETTING: Aga Khan University Hospital (AKUH). SUBJECTS: The study population consisted of a convenience sample of patients undergoing surgery for TURP (control and experimental) and health team members (nurses, physicians and others). STUDY FINDINGS: Findings showed a significant difference in variances and outcomes as a result of TURP clinical pathway intervention. The clinical pathway significantly improved all twelve nursing and physician related variances and outcomes, such as: complete documentation; delayed consultation; delayed education; and other variances. Clinical pathway intervention also significantly reduced hospital related variances, and post operative problems such as electrolyte imbalance, phlebitis, constipation, and urinary tract infection (UTI). The findings also showed significant improvement in patient and staff satisfaction, however no significant difference was observed in patient, hospital and financial related variances. The current investigation identified that successful implementation of integrated clinical pathways can help health professionals, managers and administrators to meet one of their biggest challenges in making optimal use of limited resources while delivering high quality and timely care. PMID- 17285837 TI - Effect of local refrigeration prior to venipuncture on pain related responses in school age children. AB - INTRODUCTION: Painful medical procedures are the major sources of distress among children; and for those with chronic diseases, the procedure-related pain can be worse than that of the illness itself. OBJECTIVE: The purpose of the study was to determine the effect of local refrigeration prior to venipuncture on pain-related responses in school-age children. DESIGN: Quasi-experimental study. SETTING: This study was undertaken in a paediatric emergency ward of a paediatric centre. SUBJECTS: The subjects were 80 children 6 to 12 years of age selected by purposive sampling after being referred to the paediatric emergency ward. INTERVENTIONS: Two groups were chosen for the study: the test and control groups, in order to test the effect of local coldness in reducing the pain of venipuncture. In the test group, the injection site was refrigerated for three minutes using an ice bag. In the control group, the procedure was performed according to usual routine. Physiological responses (ie. blood pressure, pulse, and respiration), behavioural responses (using the Children's Hospital of Eastern Ontario Pain Scale: CHEOPS), and subjective responses (or intensity of pain using the Oucher scale) were measured in the two groups. A non-invasive (electronic) sphygmomanometer was used before and 5 minutes after the procedure to measure the physiological responses. The measurement of behavioral responses by CHEOPS was done at two time points (during the procedure and 5 minutes after the procedure), measuring six areas of behavior: cry, facial expressions, child verbal, torso, touch and leg movement in reaction to painful stimulation. Finally, the subjective responses were measured at 5 minutes after the procedure. MAIN OUTCOME MEASURES: In this study the main outcome measures were: range of physiologic responses, and scores of behavioral and subjective responses. The study hypothesised there would be a lower score in the test group than the control group in behavioural and subjective responses and a lower range in physiologic responses. RESULTS: Results showed no significant difference between the two groups for physiological responses (before and after procedure). However behavioural responses during and after the procedure (p = 0.0011), and subjective responses after the procedure (p = 0.0097) were significantly lower (ie. the test group had lower scores in behavioural and subjective responses compared to the control group. CONCLUSION: The results of this study suggest that the use of local refrigeration prior to venipuncture can be considered an easy and effective intervention of reducing venipuncture-related pain. PMID- 17285838 TI - The clinical nurse specialist and nurse practitioner roles: room for both or take your pick? AB - OBJECTIVE: The aim of this paper is to contribute to pertinent discussions regarding advanced practice nursing roles. In particular discussion will focus on the potential implications for the developing nurse ractitioner (NP) role on the existing clinical nurse specialist (CNS) roles. SETTING: The literature presented originates primarily from the United States of America (USA), United Kingdom and Australia. Specific emphasis is placed on the psychiatric/mental health nursing context. PRIMARY ARGUMENT: Amidst the confusion in terminology to describe and explain advanced, expanded or extended nursing roles, and to distinguish between the clinical nurse specialist and the nurse practitioner, there is a need to establish clarity. The need for both clinical nurse specialist and nurse practitioner roles has been hotly debated in the USA. CONCLUSIONS: The roles of clinical nurse specialist and nurse practitioner may be complementary but fulfil different functions. It is therefore important that both roles be maintained and implemented in response to consumer and health service needs. PMID- 17285839 TI - [Applicative aspects of liquid-based cytology in cervical cancer screening]. AB - The quality of cytological services is the very heart of the prevention of cervical pathologies. Indeed, various studies have demonstrated that inadequate sampling, mistakes made in the organisational and management methods of the screening programme, and incorrect diagnoses result in unnecessarily high incidence and mortality rates. The aim of this work is to compare the effectiveness of two different methods, i.e. a conventional smear test and a liquid based ThinPrep (TP) test. Said methods were tested on a sample 453 cases diagnosed as being "Atypical Squamous Cells of Undetermined Significance"/"Atypical Glandular Cells of Undetermined Significance" according to the 1991 Bethesda System. All the women with an "Atypical Squamous Cells of Undetermined Significance "/"Atypical Glandular Cells of Undetermined Significance" cytological diagnosis were called back within 3 months for a ThinPrep test, as part of the Level 2 diagnostic controls of a cervical cancer screening programme. Of the initial diagnoses of "Atypical Squamous Cells of Undetermined Significance"/"Atypical Glandular Cells of Undetermined Significance" with a conventional smear test, 124 cases (27.4%) were classified as being adequate, while 329 (72.6%) were satisfactory, although they did have limited indicators of quality. Upon repetition of the cytology with a ThinPrep test, 322 cases (71.1%) were found to be adequate, 129 (28.4%) "suboptimal" and 2 inadequate (p < 0.0001). The main reasons for insufficient results in conventional smear tests are: bad preservation (40.2%), the presence of granulocytes (36.4%), intense phlogosis (12.1%) and erythrocytes (5.5%). In liquid based smear tests, the main indicator of quality is the absence of endocervical glandular cells (56.7%). As for the cytological diagnosis, the use of ThinPrep supplied the following results: of the 453 cases diagnosed initially as being "Atypical Squamous Cells of Undetermined Significance"/"Atypical Glandular Cells of Undetermined Significance", 371 (84.1%) were negative, 54 (11.9%) "Atypical Squamous Cells of Undetermined Significance "/"Atypical Glandular Cells of Undetermined Significance" and 18 (4%) L-SIL (p < 0.0001). Histological follow-up of the 18 cases with L-SIL confirmed the presence of a dysplastic lesion in 8 out of 12 cases (66.7%); in 4 cases there was no consistency between the cytological and histological diagnoses, and in 6 patients no biopsy had been taken. The preliminary experience of this study, although indeed carried out on a limited number of cases, appears to show that suitable training for the collection of samples in a liquid solution could improve the adequacy of the sample and thus the precision of the cytological diagnosis. PMID- 17285840 TI - [Values and limits in fine needle aspiration in the diagnosis of Warthin tumour of the parotid gland]. AB - Recent paper state that cytological diagnosis of Warthin Tumour of the parotid gland is poorly reproducible and that aspiration procedures damage the tumoral tissue as to make difficult the histological diagnosis. Aim of the present study is to review cytological sampling performed with fine needle sampling without aspiration and to compare them with the relative surgical specimens in order to determine the value of fine needle aspiration in the diagnosis of Warthin Tumour and to quantify' the damage in histological tissue. MATERIALS AND METHOD: All cases with cytological and/or histological diagnosis of Warthin Tumour during the period 1/1/98 to 30/6/04 were retrieved. In all cases both cytological and histological slides were reviewed and compared. In all cases fine needle aspiration (FNA) was performed according to the technique described by Zajdela et al. in 1987. A cytologic sample was considered diagnostic when there were in the same sample mucoid substance, lymphocytes scattered with a range of maturation and oncocytes organized in flat sheets of cells. RESULTS: 38 cases were selected corresponding to 37 patients (1 case of Warthin Tumour bilateral): all tumors were localized in the parotid gland. Fine needle sampling were 43. Nine cytological sample (20.9%) were inadequate. Sensitivity and specificity, in the preent series, had the same value, being 97.1%. A spectrum of histologic alterations were observed in 30/38 cases (79%). These alterations were squamous metaplasia (7 cases), acute and chronic hemorrhage and inflammation with multinucleated giant cells (26 cases) and granulation tissue with subsequent fibrosis (24 cases). In all cases the histologic alterations from fine needle were focal, limited to less than 20% of the tumoral area (first category of Batsakis 'classification), and did not prevent the histologic diagnosis of Warthin Tumour. CONCLUSIONS: These data suggest that fine needle aspiration without aspiration is a valuable tool for the per-operative diagnosis of Warthin Tumour. In addition it creates only minor histological changes, that always allow the histological diagnosis. PMID- 17285842 TI - Lipomatous hemangiopericytoma (adipocytic variant of solitary fibrous tumor) of the orbit. A case report with review of the literature. AB - Hemangiopericytoma (HPC) of the orbit is a rare tumor presenting with slowly progressive proptosis, ocular motility impairment and visual loss. In 1995, a newly variant of HPC termed lipomatous hemangiopericytoma (LHPC), was described. Only two cases arising in the orbit have been previously reported. The authors describe another case of orbital LHPC and discuss the clinicopathologic features, including the immunohistochemical staining profile and ultrastructural appearance of this distinctive tumor, and briefly discuss the relationship between HPC and solitary fibrous tumor of soft tissue, a neoplasm with many clinical and pathologic similarities. PMID- 17285841 TI - Expression of thyroid transcription factor 1 (TTF-1) in extra thyroidal sites: papillary thyroid carcinoma of branchial cleft cysts and thyroglossal duct cysts and struma ovarii. AB - The thyroid-associated transcription factor-1 (TTF-1) is a nuclear tissue specific protein, found only in thyroid and thyroid tumors regardless of histologic type as well as in lung carcinomas. Most ectopic thyroid tissue are found along the thyroglossal duct tract and around the bilateral main lobes of thyroid glands. Ectopic thyroid tissue within a branchial cleft cyst is a rare abnormality and papillary carcinoma arising in this tissue is extremely rare. Thyroid tissue may also be found as one of the many components of teratoma, particularly those located in the ovary. The aim of this study is to evaluate, through immunohistochemistry, the expression of TTF-1 in branchial cleft cysts with ectopic normal thyroid tissue, in primary thyroid papillary carcinomas of branchial cleft cysts and thyroglossal duct cysts and in struma ovarii, in order to evaluate the expression of this antigen in extra thyroidal sites. PMID- 17285843 TI - Perivascular epithelioid cell tumor of the uterus: a case report. AB - A case of a perivascular epithelioid cell tumor (PEComa) arising in the uterus of a 35-year-old woman is presented. Imaging studies revealed a 5 cm well circumscribed mass in the uterine fundus. The tumor was composed of clear to faintly eosinophilic, epithelioid and spindled cells. Immunohistochemically, most tumour cells were strongly positive for HMB-45, smooth muscle actin and desmine, but negative for epithelial markers, S-100 Protein and neuroendocrine markers. Reevaluation of the patient for signs of tuberous sclerosis complex after the diagnosis gave negative results. At the most recent follow-up 4 months later there was no evidence of recurrence. PMID- 17285844 TI - Thymoma with extensive necrosis: a case report and review of literature. AB - Thymoma exhibiting extensive necrosis is extremely rare and remains a diagnostic challenge for both radiologists and pathologists. We describe such a thymoma in an 18-year-old African-American female. Core needle biopsy contained only necrotic tumor tissue. A well-encapsulated 13-cm anterior mediastinal thymoma with extensive necrosis and areas of hemorrhage was resected. Microscopically, the thymus was almost completely replaced by tumor composed of plump epithelial cells with vesicular nuclei and prominent nucleoli in a background of lymphocytes and extensive necrosis. The clinical, immunohistochemical and diagnostic pitfalls of this tumor in core needle biopsies is discussed. PMID- 17285845 TI - [Comment on the article by Fulcheri E, Bulfamante G, Resta L, Taddei GL. Embryo pathology and feto-perinatal pathology in anatomo-pathologic diagnosis: what has changed and what needs to be changed]. PMID- 17285846 TI - Hemolivia mauritanica (Haemogregarinidae: Apicomplexa) infection in the tortoise Testudo graeca in the Near East with data on sporogonous development in the tick vector Hyalomna aegyptium. AB - Testudo groeca tortoises were collected in the northern and southern Golan Heights (Israeli occupied territory of south Syria), and various locations in Israel and Palestine. Hyoalomma oegyptium ticks were found only on Golan Height tortoises, and only the tortoises and ticks from the northern Golan Heights were infected with Hemolivia mouritanica. Tortoises became infected after ingesting infected ticks. Male ticks carrying sporocysts, which remain attached to tortoises for extended durations, apparently served as the source for dissemination of new infections among tortoises. Sporogenesis followed the pattern observed in the two other known species of Hemolivia, though there was some evident variation in fine-structura detail. The sutural slit detected in the H. mouritanica mature sporocyst wall was reminiscent of the suture characteristic of Coccidia of heterothermic vertebrate hosts; it could be a common ancestral character for both hemogregarines PMID- 17285847 TI - Two new species of Pseudochristianella Campbell & Beveridge, 1990 (Cestoda: Trypanorhyncha) from elasmobranch fishes from the Gulf of California, Mexico. AB - Pseudochristionella elegantissima sp. nov. (Cestoda: Trypanorhyncha) is described from the spiral valves of the rays Dasyatis brevis (Garman, 1880) and D. longus (Garman, 1880), from the Gulf of California, Mexico. Also described is P. nudisculo sp. nov. from rays Rhinobatos productus Ayres, 1854, D. longus, Myliobatis longirostris Applegate & Fitch, 1964 and Zapteryx exasperat (Jordan & Gilbert, 1880) from the same location. The species are distinguished from one another and from the only existing species within the genus, P. southwelli Campbel & Beveridge, 1990, by differences in the arrangement of bill-hooks on the external surface of the basal swelling of the tentacle and by the number of hooks in each row of the metabasasl armature. PMID- 17285848 TI - Monogeneans from Pangasiidae (Siluriformes) in Southeast Asia: X. six new species of Thaparocleidus Jain, 1952 (Ancylodiscoididae) from Pangasius micronema. AB - The examination of gill parasites from Pangasius micronemao Bleeker, 1847 (Siluriformes, Pangasiidae) in Southeast Asia revealed the presence of nine species of Monogenea. Two (Thoparocleidus brevicochleus Pariselle, Lim & Lambert, 2001 and T. sinespinoe Pariselle, Lim & Lambert, 2001) have been previously described. Among the others, six species, belonging to Thaporocleidus Jain, 1952 (Monogenea, Ancylodiscoididae) as defined by Lim (1996) and Lim et al. (2001), are considered new species: T. tacitus n. sp., T. summagracilis n. sp., T. portentosus n. sp., T rukyonii n. sp., T. durandi n. sp., and T. lebrunce n. sp. The remaining species is represented by too few individuals to be conclusively described. PMID- 17285849 TI - Helminth communities of two green frogs (Rana perezi and Rana saharica) from both shores of the Alboran Sea. AB - The helminth communities of two populations of green frogs from both shores of the Alboron Sea (Western Mediterranean) were studied. Of the 79 frogs examined for helminths, 39 individuals of the species Rano saharica were collected from Bob-Taza (Morocco), and 40 of the species Rona perezi were collected from the Natural Park of the Sierra de Grazalema (Spain). Although the species richness of helminths was identical in the two sampled areas, the differences observed in the structure of the helminth infracommunities were quite important. Statistically, significant differences were found between the species richness and the diversity of the infracommunities of R. perezi female population and the other three studied statistical populations. The helminth component communities of these two green frogs can be considered as depauperate, although their infracommunities present interactive features. PMID- 17285850 TI - [Description of the female of Phlebotomus (Larroussius) Chadlii, Rioux, Juminer & Gibily, 1966 (Diptera: Psychodidae). From an example captured from the area of Kef (Tunisia)]. AB - The female of Phlebotomus chadlii Rioux, Jumminer & Gibily, 1966 is described and illustrated for the first time from a specimen collected in El Kef region, northwest Tunisia. It was distinguished from P. ariasi by several characters of the spermathecae: 1) the enlarged portion of P. chadlii spermathecae duct appears smooth and better developed than that of P. ariasi; 2) in P. chadlii, this part comprises three quarters of the duct whereas, in P. ariasi, it covers only the half; 3) the spermathecae neck of P. chadlii is shorter than that of P. ariasi. The duct base is compatible with the large aedeagus size of P. chadlii male. Besides, the assignment of this female to the species P. chadlii is supported by: 1) the presence of males in the same area, over the last three years; 2) the total absence in this area of P. ariasi; 3) the concomitant presence, in the same trap station, of the described female with P. chadlii males. PMID- 17285851 TI - In vitro rearing Oestrus caucasicus third-instar larvae and pupae (Diptera: Oestridae) from naturally-infested Iberian ibex, Capra Pyrenaica (Artiodactyla: Bovidae). AB - Third-instar Oestrus caucasicus larvae (n = 236) obtained from Iberian ibex, Copra pyrenaica, were reared in a laboratory to obtain adult flies. They were maintained at a temperature of 21.9 +/- 2.7 degrees C and a relative humidity of 38.9 +/- 8.0 %. In all, 78 imagos emerged (33.1 %), with a sex-ratio at emergence not differing significantly from 1:1; 25 larvae did not complete pupariation. A total of 14 adult flies (17.9 % of the adults obtained) showed malformations, mainly in their wings. The pupariation period lasted around 30 hours and the pupal stage lasted on average 29.8 +/- 6.8 days. The success of pupation in both sexes was mainly determined by the weight of the larvae. Sexual dimorphism, with higher weights in females, was evident in third-instar arvae, pupae and adults. The mean longevity of adult flies was 224.8 +/- 91.4 hours and males generally survived for onger than the females. PMID- 17285852 TI - Kinetics of oestrus ovis infection and activity of adult flies. AB - Oestrus Ovis is a common sheep parasite in the Mediterranean region. This study was carried out in the Ebro River Valley near Zaragoza (northeast Spain) using tracer animals to describe the seasons when infestation is more likely. Based on that information and an analysis of the evolution of the parasite within the host, we suggest the most appropriate time for treatment. Adult instars appeared in May until November and there was a diapause beginning in October-November and as least until February, so it is suggested than sheep be treated with larvicide in December. PMID- 17285853 TI - Host-parasite relationships of monogeneans in gills of Astyanax altiparanae and Rhamdia quelen of the Sao Francisco Verdadeiro River, Brazil. AB - This study investigates the ecology of monogenean gill parasites of Aslyanax altiparanae Garutti & Britski, 2000 and Rhamdia quelen (Quoy & Gaimard, 1824) in a stretch of the Sao Francisco Verdadeiro River, Parana, Brazil. Statistical and ecological indices were used to examine observed levels of parasitism in relation to host and environmental characteristics. A. altiparance and R. quelen had infestation intensities of 2.8 and 23.1 parasites per fish, respectively. The only significant environmental influence was observed at the upstream station for R. quelen. For both host species, parasitized and non-parasitized individuals presented similar weight-ength relationships. Parasitized individuals had dispersed K,, values indicating abnormal conditions. The low levels of parasitism observed in this study suggest that the environment is relatively undisturbed. Additional studies should compare these two species and their respective parasites following completion of the hydroelectric headquarters planned for construction in this stretch of the Sao Francisco Verdoadeiro River. PMID- 17285854 TI - Comparative evaluation of western blotting in hepatic and pulmonary cystic echinococcosis. AB - Many serological tests are widely used in the diagnosis of cystic echinococcosis (CE), caused by the larval stages of Echinococcus granulosus. The present study was carried for differentiation between hepatic and pulmonary cystic echinococcosis by Western Blotting (WB). A total of 121 sera from patients with hepatic CE (37), pulmonary CE (31) and controls (53; consisting of six healthy, seven Hymenolepis nana infection, 20 hepatic and 20 pulmonary diseases other than CE) were examined. In all of the CE patients, E. gronulosus infection was confirmed by surgical intervention. Sera were previously tested using IHA and ELISA to detect the E. gronulosus specific antibodies. Sera from hepatic cases of CE reacted with 16 polypeptides of 6-116 kDa and sera from pulmonary cases of CE reacted with 14 polypeptides of 4-130 kDa by Western Blotting. The WB test enabled the detection of antibodies in the hepatic CE samples for proteins of 24, 32 34, 44-46 and 52-54 kDa in molecular weight in 78.4%, 75.7%, 78.4% and 89.2% of the patients, respectively. In the pulmonary CE samples sera WB test enabled the detection of antibodies 24, 44-46, 100, 110, 116 and 120 124 kDa in molecular weight in 81.3%, 75.0%, 87.5%, 71.9%, 84.4% and 65.6% of the patients, respectively. We indicated that the antigenic components of high molecular weight can be good candidates for differentiation of hepatic CE from pulmonary CE. PMID- 17285855 TI - Very high DDT-resistant population of Anopheles pharoensis Theobald (Diptera: Culicidae) from Gorgora, northern Ethiopia. AB - Standard WHO insecticide bioassay tests were carried out in Gorgora, northern Ethiopia to evaluate the susceptibility status of Anopheles pharoensis Theobald for the insecticides DDT, malathion, permethrin and deltamethrin. The mortality and when appropriate knockdown effect of the insecticides were observed. The results indicated that this species was resistant to DDT. A high mortality was obtained after exposure to permethrin and deltamethrin but below 97 % which is the limit for susceptibility according to WHO. A prolonged knockdown time was noted for DDT and the two pyrethroids. An. phoaroensis was found to be susceptible to malathion. PMID- 17285856 TI - [Relationship between CO II gene of mtDNA of Lucilia sericata and latitude interval]. AB - OBJECTIVE: To deduce the region that the geographical species of Lucilia sericata come from and determine the scene of crime (SOC) based on the gene analysis of mtDNA CO II. METHODS: A 635 bp region for CO II of 4 Lucilia sericata (belong to 2 geographical species) were collected and sequenced, compared with the data of GenBank. A neighbour-joining tree with the Tamura and Nei model was constructed by MEGA2.1 package. The number of inherit intervals of inner-species were analyzes by Kimura's two-parameter model and used for construction the relationships between hereditary and latitude interval by SPSS10.5 soft. RESULTS: It showed that they had the relationships between inherit and latitude interval for the 8 geographical species of Lucilia sericata for CO II. CONCLUSION: This method can be the evidence deducing the region that the geographical species of Lucilia sericata come from and further to determine the scene of crime (SOC). PMID- 17285857 TI - [Expression of cathepsin-B and -D in rat's brain after traumatic brain injury]. AB - OBJECTIVE: To study the expression of cathepsin-B and -D in different time point after traumatic brain injury. METHODS: Traumatic brain injury (TBI) model was established on rats, cathepsin-B and cathepsin-D immunofluorescence staining and confocal microscope analysis were performed. Positive cells were counted by confocal microscope and image analysis techniques were used to determine the morphological changes in each group. RESULTS: Immunofluorescence staining results showed that cathepsin-B was activated 1 hour after TBI while cathepsin-D was not activated until 12hour after TBI. Both of them got to their peak during 4 to 8days, and kept a high level of activating 32days after TBI. Cathepsin-B and -D positive cells did not merge with caspase-3 positive cells until 6 h after TBI. CONCLUSION: Cathepsin-B and -D could be the diagnostic markers of TBI and can estimating time course of lateral TBI. They blocked caspase-3 activation at the beginning period after TBI and started to promote cell death with caspase-3 6 h after TBI. PMID- 17285858 TI - [Expression of HIF1-alpha on myocardium and lung in rats model of asphyxia death]. AB - OBJECTIVE: To investigate the expression of HIF1-alpha in heart and lung tissue died from asphyxia. METHODS: The rats model of asphyxia death was constructed by hanging, different asphyxia groups and control group sets were made according the postmortem time (0,2,6,24 h), immunohistochemistry and half-quantitative RT-PCR methods were used to investigate expression of HIF1-alpha and mRNA changes on heart and lung tissue. RESULTS: The positive staining of HIF1-alpha could be observed in the myocardium and lung tissue. Significant differences were found between the groups of asphyxia and their corresponding control group. HIF1-alpha expression was found in all the asphyxia groups while it was only expressed in the control groups of 2 h, 6 h and 24 h. Nucleic positive staining could be detected in all the asphyxia groups but none was found in the control groups. RT PCR showed that the expression of mRNA between 0 h asphyxia group and 0 h control group were equal in both cardic muscle and lung, but elevated expression in groups of 2,6,24h compared to their control groups. CONCLUSION: The nuclear positive staining of HIF1-alpha in heart and lung can be a special character of suffocation death. PMID- 17285859 TI - [Forensic pathological significance of immunohistochemical study with CX43 in rats on early myocardial ischaemia]. AB - OBJECTIVE: To explore one of evidence for pathologic diagnosis of early myocardial ischaemia. METHODS: Rats were ligated of the left coronary artery according to a previously documented technique, and heart tissue was sampled at different ischaemia time. The expression of CX43 in myocardial cell was detected by Immunohistochemistry. RESULTS: It is showed that the distribution and amount of CX43 positive staining in each group of the myocardial ischaemia was different from that of the control group. CONCLUSION: The changes of CX43 detected by Immunohistochemical methods may be helpful for the diagnosis of early myocardial ischaemia, but further pathologic investigation and research is necessary. PMID- 17285860 TI - [Immunohistochemical study on contents of beta-amyloid, alpha-actin and collagen IV in cerebral small vessels with unknown type of pathological lesion]. AB - OBJECTIVE: To investigate the structural characteristics of the cerebral small vessels with an unknown type of pathological lesion (UTPL). METHODS: Contents of beta-amyloid, alpha-actin and collagen IV in cerebral small vessels with UTPL were studied by Congo red staining, immunohistochemical staining and computer image analysis. RESULTS: The low expression levels of alpha-actin and collagen IV (P<0.05) were observed in tunica media of the vessels with UTPL, and no positive expression of beta-amyloid (P>0.05) was observed in these vessel walls. The expressions of proteins mentioned above in UTPL were different from those of cerebral amyloid angiopathy(CAA) and hyaline arteriolosclerosis. CONCLUSION: UTPL was different from CAA or hyaline arteriolosclerosis in pathologic feature. PMID- 17285861 TI - [Develop a statistics analysis software in population genetics using VBA language]. AB - OBJECTIVE: To develop a statistics analysis software that can be used in STR population genetics for the purpose of promoting and fastening the basic research of STR population genetics. METHODS: Selecting the Microsoft VBA for Excel, which is simple and easy to use, as the program language and using its macro function to develop a statistics analysis software used in STR population genetics. RESULTS: The software "Easy STR Genetics" based on VBA language, by which the population genetic analysis of STR data can be made, were developed. CONCLUSION: The developed software "Easy STR Genetics" based on VBA language, can be spread in the domain of STR population genetics research domestically and internationally, due to its feature of full function, good compatibility for different formats of input data, distinct and easy to understand outputs for statistics and calculation results. PMID- 17285862 TI - [Evaluation of uncertainty in determination of heroin by GC]. AB - OBJECTIVE: To estimate the inevitable uncertainty of determining heroin by GC. METHODS: The source of the uncertainty was confirmed from the determining procedure. Each component's uncertainty was calculated. The combined uncertainty was then obtained by synthesizing the uncertainties of various components variables, and the expand uncertainty was finally obtained. RESULTS: The uncertainty of repeated measurement was greater than other uncertainty components introduced by balance,content vessels and instruments in determining heroin. CONCLUSION: The errors of repeated measurement and GC instrumental were confirmed as the major sources of uncertainty in determining heroin by GC. PMID- 17285863 TI - [A color test for rapid screening of gamma-hydroxybutyric acid (GHB) and gamma butyrolactone (GBL) in drink and urine]. AB - OBJECTIVE: A rapid color test for screening gamma-hydroxybutyric acid (GHB) and its precursor gamma-butyrolactone(GBL) was investigated in drink and urine samples. METHODS: In an acidic solution, GHB was converted to GBL, which reacted with hydroxylamine hydrochloride in presence of sodium hydroxide, forming hydroxamate. A purple complex was formed when hydroxamate reacted with ferric chloride in acidic condition. RESULTS: Detection limit concentrations of GHB in drinks were between 0.5-2 mg/mL, less than the popular abuse concentrations of GHB. This method was usable for urine, with detection limit concentration 0.5 mg/mL. Interferences of common organic solvents and narcotics and depressants were surveyed. CONCLUSION: This method is simple, safe, and rapid; it facilitates rapid screening of GHB and GBL in clinic and forensic laboratories. PMID- 17285864 TI - [Determination of tramadol hydrochloride in serum samples by disk solid phase extraction and gas chromatography-mass spectrometry in selected ion monitoring]. AB - OBJECTIVE: Disk solid phase extraction (SPE) was assessed for tramadol hydrochloride from serum. METHODS: The SPE was performed with SPEC C18AR/MP3 Disk SPE cartridge, offering hydrophobic C18 and strong cation ionic exchange interactions for the analytes, before being added into extraction column, 1 mL serum was diluted by 2 mL 0.1 mol/L phosphate buffer solution (pH 6) and the eluent was ethyl acetate containing 2% ammonia. Then SKF525 was added as internal standard into samples, which would be extracted simultaneously with analyte,quantitatively, determined by GC/MS/SIM. RESULTS: The extraction recovery of tramadol hydrochloride was 98.9%, 92.5% and 84.8% for serum samples with corresponding amounts of standard addition of 0.1 microg/mL, 0.2 microg/mL and 0.5 microg/mL. And RSD measured 5 times was 3.2%, 8.7% and 10.9% respectively. The linear range varied from 0.1 microg/mL to 4 microg/mL. The multinomial regression correlation coefficient (r2) equaled 0.9939, and the detection limit was 21 ng/mL. After the same extraction column was continuously used for 5 times, there was no jam, pollution and decline of recovery and RSD. CONCLUSION: This method is suitable for forensic toxicological analysis. PMID- 17285865 TI - [Causes of sudden death during the process of venous infusion: an analysis of 12 cases]. AB - Twelve cases died during the process of venous infusion were collected from 208 autopsy cases during the period of 2002-2004 in our center. The rate was 5.8% (12/208). In these 12 cases, 8 occurred in countryside clinic with poor medical condition. Negligence to take care of the indications and contraindications of venous infusion was the main cause of these accidents. Autopsy data showed that the cause of sudden death of 9 cases were related to the venous infusion directly or indirectly. The other 3 cases were died from original diseases of these patients and the time of these deaths was time of coincidence occasionally with the time of venous infusion. PMID- 17285866 TI - [Comparative study of two methods of DNA extraction from different colour costal cartilage in STR genotyping]. AB - OBJECTIVE: To compare the effectiveness of two methods of DNA extraction from different colour costal cartilages in STR genotyping. METHODS: DNA fragments were extracted from costal cartilages of different colour of 30 corrupt corpses using Chelex-100 and Phenol-Chloroform methods. STR loci were analyzed by ABI 3100 genetic analyzer after PCR amplification by using Profiler Plus kit. RESULTS: STR loci were completely detected in all 30 samlpes of costal cartilages when using Phenol-Chloroform DNA extraction methods. While using Chelex-100 methods, all STR loci were identified in 22 cases (11 white, 8 light-yellow and 3 yellow cases). Partial STR loci were detected in 7 cases (3 yellow and 4 yellow-brown cases) and none in 1 brown-black cases. CONCLUSION: Suitable DNA extracion methods will be chosen depends on the colour of costal cartilage. Phenol-Chloroform methods is more effective in STR genotyping especially in dark colour costal cartilage cases. PMID- 17285867 TI - [Determining postmortem interval by accumulated temperature method]. AB - The experience of bug's growing and accumulated temperatures were important ways for determination of postmortem interval in forensic science. Here we used reverse accumulated temperature methods to estimate postmortem interval and made accordant result with their true time. PMID- 17285868 TI - [Relation of conversion between acreage and length of wound or scar]. AB - We discovered that the surface area and the length of body wounds or scar can not be calculated each other in the existing standards. It may be unfair to some assessments of body surface impairment. It is necessary to raise a means to solve this problem and provide the reference for the colleague. PMID- 17285869 TI - [Present study on the forensic medicine diagnosis of the sudden erethistic death]. AB - The death caused of anaphylactic shock is common in clinical medicine and medicolegal expertise, but it is a nodus to diagnose sudden death from allergy. In recent years, to provide objective and precise morphological evidence and index of diagnosis for sudden death from allergy, scholars of internal and overseas studied the content of IgE, HT, mast cell tryptase and SP in the serum of the death died of anaphylactic shock, and their immune express in lung and stomach intestine. In this text we reviewed the present study and existing problems of the forensic medicine diagnosis of the sudden erethistic death. PMID- 17285870 TI - [Advances of forensic entomology in China]. AB - Forensic entomology is a branch of forensic medicine, which applies studies of insects and arthropods to getting evidence for court and has an analogous advantage in the estimation of the postmortem interval (PMI) and other questions of forensic relevance. The paper expounds its definition and contents and reviews some progress of the studies in some aspects in China such as the constitution and succession of insect community on the different cadavers, the applications of morphological features of insects and the technology of analysis of deoxyribonucleic acid (DNA) in forensic entomology, and forensic entomological toxicology etc. PMID- 17285871 TI - [Recent progress in research on positional asphyxia of restraint]. AB - Positional asphyxia of restraint means that when an individual was limited in an abnormal body position, asphyxia would take place owing to the disorder of spontaneous respiratory function, and finally it lead to die. So, it belongs to a special type of the mechanical asphyxia. From the cases reported, we could found that it would take place in several conditions. Because the cases were not caused enough recognition, the study has been researched carefully only in recent years. Following the more cases reported, many experts of forensic medicine had investigated it on the mechanism of death and the standard of identification, but they could not reach to agreements. So, they have changed the directions of the researches, began to value the factors of risk and research how to avoid it. In the following text, the mechanism of death, factors of risk, preventive methods, standard of identification and prospecting of positional asphyxia of restraint were reviewed. PMID- 17285872 TI - [DNA extraction from formalin fixed and paraffin embedded tissues]. AB - Owing to the DNA degradation induced by formalin and the obstruction of paraffin to DNA extraction, it is difficult to recover high-quality DNA from Formalin fixed and paraffin embedded tissue (FFPET). In recent years, a lot of researches indicate that the DNA extraction from FFPET can be developed by improving the pretreatment, optimizing the digestion condition of proteinase, simplizing the procedures of the DNA extraction, purifying the extracted DNA and so on, which may pave a way for popularizing FFPET in DNA analysis. PMID- 17285873 TI - Testing for the presence of 1/f noise in continuation tapping data. AB - A number of recent papers have suggested that the series of time intervals produced in continuation tapping may have fractal properties. This proposition, nevertheless, was only based on the visual appraisal of graphical results, and was not statistically supported. In the present study, we applied the ARMA/ARFIMA modeling procedures proposed by Wagenmakers, Farrell, and Ratcliff (2005) to test for the presence of long-range dependencies in continuation tapping data. Our results demonstrate the presence of long-range dependencies in most series and offer strong support for the hypothesis that fluctuations in tapping series are fractal in nature. PMID- 17285875 TI - Long-term priming of neighbours biases the word recognition process: evidence from a lexical decision task. AB - The role of orthographically similar words (i.e., neighbours) in the word recognition process has been studied extensively using short-term priming paradigms (e.g., Colombo, 1986). Here we demonstrate that long-term effects of neighbour priming can also be obtained. Experiment 1 showed that prior study of a neighbour (e.g., TANGO) increased later lexical decision performance for similar words (e.g., MANGO), but decreased performance for similar pseudowords (e.g., LANGO). Experiment 2 replicated this bias effect and showed that the increase in lexical decision performance due to neighbour priming is selectively due to words from a relatively sparse neighbourhood. Explanations of the bias effect in terms of lexical activation and episodic memory retrieval are discussed. PMID- 17285877 TI - Temporal information processing and pitch discrimination as predictors of general intelligence. AB - In the present study, the relationship between performance on temporal and pitch discrimination and psychometric intelligence was investigated in a sample of 164 participants by means of an experimental dissociation paradigm. Performance on both temporal and pitch discrimination was substantially related to psychometric intelligence (r=.43 and r =.39). Regression analysis and structural equation modeling suggested that both psychophysical domains can be considered as valid predictors of psychometric intelligence. Both predictor variables contributed substantial portions of both shared and unique variance to the prediction of individual differences in psychometric intelligence. Thus, the present study yielded further evidence for a functional relationship between psychometric intelligence and temporal as well as pitch discrimination acuity. Eventually, findings are consistent with the notion that temporal discrimination - in addition to general aspects of sensory discrimination shared with pitch discrimination reflects specific intelligence-related aspects of neural information processing. PMID- 17285878 TI - The locus of location repetition latency effects. AB - We examined the processing locus (location vs. response) of location repetition effects in terms of the event [target (t) or distractor (d)] that initially occupied and then re-occupied the repeated location (i.e., t-to-t, t-to-d, d-to t, d-to-d). Trials were presented in pairs (prime, then probe) and 2:1 location to-response mappings were used. Generally, for all repetition conditions, perceptual processing at the repeated location itself was facilitated (location locus), while re-activated responses delayed output production (response locus). More specifically, perceptual facilitation observed for a repeated location was independent of the kind of processing (i.e., t or d) that occurred earlier, suggesting that it is not the labeling of locations as relevant or irrelevant that determines location repetition effects. Response production was significantly slowed only when a just-inhibited response had then to be executed, which supported the view that the spatial negative priming effect has a response locus. PMID- 17285879 TI - Neural synchrony in stochastic resonance, attention, and consciousness. AB - We describe briefly three of our lab's ongoing projects studying the role of neural synchrony in human perception and cognition. These projects arise from two main interests: the role of noise both in human perception and in neural synchrony, and neural synchrony as a basis for integration of functional modules in the brain. Our experimental work on these topics began with a study of the possibility that noise-influenced neural synchrony might be responsible for the fact that small amounts of noise added to weak signals can enhance their detectability (stochastic resonance). We are also studying the role of neural synchrony in attention and consciousness in several paradigms. On the basis of our own and related work by others, we conclude that (1) neural synchrony plays an important role in the integration of functional modules in the brain and (2) neural synchrony is profoundly affected and possibly regulated, in part, by the "noisiness" of the brain. PMID- 17285880 TI - Canadian ICU Collaborative: our beginning, our partners and our future. PMID- 17285882 TI - Reflections on critical care emergency preparedness: the necessity of planned education and leadership training for nurses. AB - ICU nurses who are involved in pandemic planning must advocate for the education and training they need to assume clinical leadership roles in emergency situations such as an infectious disease outbreak. Although many ICU nurses do advance to become clinical leaders, preparation is often inadequate and sometimes absent. This article focuses on two aspects of preparedness: the further development and integration of leadership competencies into day-to-day practice, and education and training using a computerized simulator. PMID- 17285881 TI - Mycotic aneurysm as a result of severe salmonella infection in the adult intensive care unit: two case studies. AB - Salmonella infections are relatively common and are generally associated with contaminated food products. Common clinical manifestations include fever, bacteremia, and chronic permanent asymptomatic colonization of the bowel (Schneider, Krulls-Munch, & Knorig, 2004). However, a small percentage of all patients with salmonella bacteremia may present with vascular infections in the form of an aneurysm (Cohen, O'Brien, Schoenbaum, and Medeiros, 1978; Shimoni et al., 1999). While it is extremely rare for those who work in the intensive care unit (ICU) to care for such patients, it is essential for health care professionals to recognize this disease in order to make a rapid diagnosis to prevent complications, such as mycotic aneurysm. This article is framed around two patients who presented to the same ICU following surgical intervention. The etiology of salmonella bacteremia, mycotic aneurysm, the risk factors, diagnosis, and treatment are discussed. PMID- 17285883 TI - Secondary lines require "primary" attention. AB - An incident report received from an intensive care unit involving the administration of a secondary infusion is reprinted, with permission, and includes material from an ISMP Canada Safety Bulletin (ISMP Canada, 2005). The incident highlights a general shortcoming of many infusion pumps: lack of the capability to recognize primary versus secondary infusions. Reliance on practitioner vigilance to ensure appropriate administration adds to their already demanding practice. Secondary lines require "primary" attention from manufacturers to enhance infusion pump design and, in the interim, by all practitioners using infusion pumps with such limitations. PMID- 17285884 TI - Transient myeloproliferative disorder associated with trisomy 21. PMID- 17285885 TI - Cloacal exstrophy: a case study. PMID- 17285886 TI - Neonatal abstinence syndrome: reconstructing the evidence. PMID- 17285887 TI - Congenital nephrotic syndrome. AB - When presented with an edematous infant who may be experiencing a severe infection, particularly an unusual one, it is important to include nephrotic syndrome in the differential diagnosis. Because drastic measures may be required to manage this illness, it is important to be able to recognize symptoms, compile needed diagnostic data, and commence appropriate treatment. A referred pediatric nephrologist can aid in diagnosis, direct management, and educate and support parents. The nephrologist is also instrumental in guiding ongoing care and preparing the infant for transplantation when it becomes necessary. PMID- 17285889 TI - A tool for guiding clinical decisions. PMID- 17285888 TI - Immunomodulation, Part V: probiotics. AB - The five-part "Pointers in Practical Pharmacology" immunomodulation series has presented some of the agents researchers are investigating in hopes of finding the means to effectively prevent and treat infectious processes in neonates. The phosphodiesterase inhibitor pentoxifylline appears promising, but large, randomized, clinical trials are still lacking. So far, there is no clear evidence to support the use of G-CSF for either the prevention or the treatment of sepsis. The results of a large, randomized, clinical trial of G-CSF in the United Kingdom are pending. Although intravenous immunoglobulin (IVIG) therapy does not appear to be useful in the prevention of sepsis, its effectiveness in the treatment of sepsis is uncertain. It is hoped that the results of the International Neonatal Immunotherapy Study will provide definitive answers regarding treatment of sepsis with IVIG. The "conditionally essential" amino acid glutamine administered either enterally or parenterally does not make a difference in the rate of systemic infection or NEC in very low birth weight infants. Finally, probiotics appear promising as documented by at least two of the three randomized, clinical trials described here. As the search continues for agents to enhance the neonate's immune system and prevent and treat infectious diseases, remember that our best prevention tool is excellent and consistent hand hygiene. PMID- 17285890 TI - Life's lessons. PMID- 17285892 TI - Unwrapping data standards. PMID- 17285891 TI - Quality healthcare data and information. PMID- 17285893 TI - Public health: a special case for data standards. PMID- 17285894 TI - E-prescribing effects. Pilot project studies e-prescribing standards in long-term care. PMID- 17285895 TI - Seasoning your compliance plan with PEPPER. How to read PEPPER data on payment errors. PMID- 17285896 TI - Brailer to HIM: continue 'larger, louder, and faster'. PMID- 17285897 TI - House approves changes to membership categories. Issue forums envision HIM's future. PMID- 17285898 TI - Is your electronic record a legal record? PMID- 17285899 TI - Student academy focuses on getting that first job. PMID- 17285900 TI - Foundational concepts of the legal EHR. PMID- 17285901 TI - Lowering costs, protecting data through content-based e-mail encryption. PMID- 17285902 TI - Needed: data content standards. Data content standards streamline data reporting for performance measurement initiatives. PMID- 17285904 TI - Guidelines for EHR documentation to prevent fraud. PMID- 17285903 TI - Ensuring privacy and security in home health. PMID- 17285905 TI - Are you ready for POA reporting? PMID- 17285906 TI - Data capture for performance measures: what coders need to know. PMID- 17285907 TI - The power of clinical document specialists. New role combines clinical, coding knowledge to improve documentation. PMID- 17285908 TI - [Wellness alone is not enough]. PMID- 17285909 TI - [Burnout. Preventing the "infarct of the soul"]. PMID- 17285910 TI - [Coaching in order to prevent Burnout]]. PMID- 17285911 TI - [Developing a new mode. Building and examining nursing quality]. PMID- 17285912 TI - [He who never has no voice gets appointed]. PMID- 17285913 TI - [Health promotion. More opportunity for construction for the perplexed]. PMID- 17285914 TI - [Isolation]. PMID- 17285915 TI - [Race problems in nursing]. PMID- 17285916 TI - ["But everybody does it" can be helpful]. PMID- 17285917 TI - [The greed that is among us]. PMID- 17285918 TI - [Alternatives in psychiatry. Therapeutic massage and the role of the nurse]. PMID- 17285919 TI - [Taking care of a newborn during weaning. The future for the the baby and the family]. PMID- 17285920 TI - [Object or subject. Mother language, "new" language?]. PMID- 17285921 TI - [Collaboration with men of the church. Prayer of liberation]. PMID- 17285922 TI - [The flight of Icarus]. PMID- 17285923 TI - TPM's first 10 years. PMID- 17285924 TI - New midwives will regain the balance. PMID- 17285925 TI - Mental healthcare: not just for specialists. PMID- 17285926 TI - Speech to Rita: giving birth to a voice. PMID- 17285927 TI - Giving emotional pain a name. PMID- 17285929 TI - Assessing cervical dilatation without VEs: watching the purple line. PMID- 17285928 TI - Listening to women in the Highlands. PMID- 17285930 TI - Midwifery basics: women's health needs (4). Breast health. PMID- 17285931 TI - Can midwives prevent shoulder dystocia? PMID- 17285932 TI - Birth and the earth. PMID- 17285933 TI - View from the river. PMID- 17285934 TI - Wood bark as packing material in a biofilter used for air treatment. AB - Biotechnology has been applied to find green and low cost environmental processes. In the waste gas treatments (odours and volatile organic compounds VOC) one of the main biological systems used is biofilters. This technology works at normal operating conditions of temperature and pressure, and therefore it is relatively cheap with high efficiencies when the waste gas is characterized by high flow and low pollutant concentration. The aim of this work is to use wood barks (Pinus) as packing material in the biofilter. For this purpose, the influence of various parameters such as residence time of the gas and pollutant loads on removal efficiencies was studied for a biofilter pilot unit. Ethanol, methyl ethyl ketone, dichloromethane and toluene were used as pollutant compounds, because they are representative of both volatile organic compounds. Packing material stability and good biodegradation performances were found. PMID- 17285935 TI - Kinetic and mass balance analysis of constructed wetlands treating landfill leachate. AB - Experiments were conducted to investigate the feasibility of applying constructed wetlands to treat a sanitary landfill leachate containing high nitrogen (TN) and bacterial contents. Two-pilot scale subsurface-flow constructed wetland (SFCW) units located at the Asian Institute of Technology, Thailand, campus, were fed with a synthetic wastewater and landfill leachate collected from a nearby sanitary landfill. Under the tropical conditions (temperature of about 30 degrees C), the SFCW units operating at the hydraulic retention time(HRT) of 8 days yielded the best treatment efficiencies with BOD, removal of 91%, TN removal of 96%, total and fecal coliforms (TC and FC) removal of more than 99% and cadmium removal of 99.7%. The treatment performance was found to follow first-order reaction rate, in which the k20 values of BOD5, COD, TN, TC, FC and Cd were 0.201, 0.121, 0.247, 0.346, 0.354 and 0.690 d(-1), respectively. Mass balance analysis, based on TN contents of the plant biomass and dissolved oxygen (DO) and oxidation- reduction potential (ORP) values, suggested that 88% of the input TN were uptaken by the plant biomass; 8% removed by nitrification-denitrification reactions and adsorption on the wetland media, while the remaining 4% were discharged with the effluent. PMID- 17285936 TI - Estimating pollutant removal requirements for landfills in the UK: I. Benchmark study and characteristics of waste treatment technologies. AB - Introduction of the EU Landfill Directive is having a significant impact on waste management in the UK and in other member states that have relied on landfilling. This paper considers the length of the aftercare period required by the municipal solid waste streams that the UK will most probably generate following implementation of the Landfill Directive. Data were derived from literature to identify properties of residues from the most likely treatment processes and the probable management times these residues will require within the landfill environment were then modelled. Results suggest that for chloride the relevant water quality standard (250 mg l(-1)) will be achieved with a management period of 40 years and for lead (0.1 mg I(-1)), 240 years. This has considerable implications for the sustainability of landfill and suggests that current timescales for aftercare of landfills may be inadequate. PMID- 17285937 TI - Estimating pollutant removal requirements for landfills in the UK: II. Model development. AB - A modelling methodology using a leachate source term has been produced for estimating the timescales for achieving environmental equilibrium status for landfilled waste. Results are reported as the period of active management required for modelled scenarios of non-flushed and flushed sites for a range of pre-filling treatments. The base scenario against which results were evaluated was raw municipal solid waste (MSW) for which only cadmium failed to reach equilibrium. Flushed raw MSW met our criteria for stabilisation with active leachate management for 40 years, subject to each of the leachate species being present at or below their average UK concentrations. Stable non-reactive wastes, meeting EU waste acceptance criteria, fared badly in the non-flushed scenario, with only two species stabilising after a management period within 1000 years and the majority requiring > 2000 years of active leachate management. The flushing scenarios showed only a marginal improvement, with arsenic still persisting beyond 2000 years management even with an additional 500 mm y(-1) of infiltration. The stabilisation time for mechanically sorted organic residues (without flushing) was high, and even with flushing, arsenic and chromium appeared to remain a problem. Two mechanical biological treatment (MBT) scenarios were examined, with medium and high intensity composting. Both were subjected to the non-flushing and flushing scenarios. The non-flushing case of both options fell short of the basic requirements of achieving equilibrium within decades. The intense composting option with minimal flushing appeared to create a scenario where equilibrium could be achieved. For incinerator bottom ash (raw and subjected to various treatments), antimony, copper, chloride and sulphate were the main controls on achieving equilibrium, irrespective of treatment type. Flushing at higher flushing rates (500 mm y(-1)) failed to demonstrate a significant reduction in the management period required. PMID- 17285938 TI - An approach to the measurement of decay, active fraction of biomass and extracellular polymeric substances: applied to hydrogen-driven denitrification. AB - A general method for measurement of active biomass and decay coefficient and Extracellular polymeric substances (EPS) concentration in steady-state biomass was developed. The model was applied to the process of hydrogenotrophic denitrification in order to measure biomass constituents and decay and yield coefficients. It was found that steady-state biomass obtained after operation at 20 day solids retention time (SRT) was composed of 41% active biomass, 25.6% cell debris and 33.4% extracellular polymeric substance. The value of 0.041 d(-1), and 0.27 mg active biomass per mg NO3-N were obtained for decay coefficient and true yield, respectively. PMID- 17285939 TI - Removal of an endocrine disrupting chemical (17alpha-ethinyloestradiol) from wastewater effluent by activated carbon adsorption: effects of activated carbon type and competitive adsorption. AB - Granular activated carbon has been extensively used for the adsorption of organic micropollutants for potable water production. In this study the removal of an endocrine disrupting chemical from wastewater final effluent by three types of granular activated carbon (wood, coconut and coal based) has been investigated in batch adsorption experiments and correlated with the removal of chemical oxygen demand (COD), total organic carbon (TOC) and ultraviolet absorbance (UV). The results obtained demonstrated 17alpha-ethinyloestradiol (EE2) removals of 98.6%, 99.3%, and 96.4% were achieved by the coal based (ACo), coconut based (ACn) and wood based (AWd) carbons respectively at the lowest dose of carbon (0.1gl(-1)). The other adsorbates investigated all exhibited good removal. At an equilibrium concentration of 7mgl(-1) the COD adsorption capacities were 3.16mg g(-1), 4.8 mg g(-1) and 7.1 mg g(-1) for the wood, coconut and coal based carbons respectively. Overall, the order of removal efficiency of EE2 and the other adsorbates for the three activated carbons was ACn > ACo > AWd. The adsorption capacities of the carbons were found to be reduced by the effects of other competing adsorbates in the wastewater effluent. PMID- 17285940 TI - Olive oil mill wastewaters pollution abatement by physical treatments and biodegradation with Phanerochaetae chrysosporium. AB - This paper discusses decolorization and chemical oxygen demand (COD) abatement in olive mill wastewaters (OMW) by Phanerochaetae chrysosporium grown in static, suspended and immobilised cultures. When P chrysosporium is used in cultures, no decolorization of crude OMW is observed. Decolorization occurs only after removal of polyphenols by adsorption on wood sawdust, which allows for removal of 39% of polyphenols. The use of High lignin peroxides (Lip) producing medium, yields the highest OMW decolorization and COD removal efficiencies. The use of P. chrysosporium immobilized on polyurethane foam leads to significant abatements of OMW polluting characteristics. In fact, chemical oxygen demand (COD), Biological oxygen demand (BOD5) and polyphenols contents are significantly reduced. In addition, a significant effluent decolorization is obvious. PMID- 17285941 TI - Relationship between Cu and Zn extractable foliar contents and BCR sequential extraction in soil treated with organic amendments. AB - The application of organic wastes to soils, such as municipal solid waste compost (MSWC) or treated urban sewage sludge (USS) is a current practice for maintaining soil organic matter, reclaiming degraded soils and supplying plant nutrients. Since USS and MSWC may contain organic contaminants, heavy metals or pathogens, this practice represents a potential problem to the environment. In the case of heavy metals both bioavailability and toxicity seems to be critically dependent on the chemical form of the element. In this work, a pot experiment was carried out with different levels of MSWC and USS, as well as an inorganic solution of Cu and Zn. The aim was to obtain information about their bioavailability, mobility and toxicity and correlation among the different soil extracted fractions (F1- Exchangeable metal associated with carbonated phases, F2--Reducible metal or associated with Fe and Mn oxides, F3--Oxidizable metal bound to organic matter) with the Cu and Zn foliar (Cu(F) and Zn(F)) and pseudo totals contents (Cu(Ptotal) and Zn(Ptotal)), using the BCR sequential and aqua regia extraction procedure. Both of these methods were adequate to predict the Cu and Zn available to the plant, as high values on the Cu(F)-Cu(sigma123), Cu(F)-Cu(Ptotal), Zn(F) Zn(sigma123) and Zn(F)-Zn(Ptotal) correlations were verified. Copper bounded mainly to F3, while Zn bounded to F1, F2 and F3 fractions and the regression analysis revelled that Cu and Zn ryegrass absorption were made mainly on F1 and F3 for Cu and F1 for Zn. PMID- 17285942 TI - Nitrogen compounds transformation in the biological filter by means of direct energy supply to the biofilm. AB - The aim of the research was to determine the effect that direct energy supply to the biofilm, which was attached to the packing with its temperature raised, exerts on the course of nitric compounds changes. The experiment was conducted in a laboratory scale. A model reactor which allowed smooth regulations of the packing temperature was used in the experiment. The energy supply was based on the emission of thermal radiation through the reactor's packing to the biofilm. On the basis of the conducted tests it has been found that such a technological solution improves the efficiency of wastewater treatment, nitrification processes in particular. The temperature range between 20 degrees C and 25 degrees C appeared to be optimal for nitrification. At temperatures higher than 25 degrees C anoxic spheres were generated in the deeper layers of the biofilm, which is proved by denitrification. PMID- 17285943 TI - Diversity of biogeochemical cycling genes from Puget Sound sediments using DNA microarrays. AB - Oligonucleotide-based microarray permits the simultaneous analysis of thousands of genes on a single chip, so that a better picture of the interactions among thousands of genes can be investigated at the same time. Our oligo microchips contained 763 50-mer probes that scan the region of different functional genes encoding amoA, pmoA, nirS, nirK, nifH, and dsrAB. These genes code for key enzymes in the ecosystem processes of nitrification, methane oxidation, denitrification, nitrogen fixation and sulfur reduction, respectively. We used these oligochips to characterize the distribution of the above genes from Puget Sound sediments at different depths. The composition and distribution of genes from shallower sediments (depths 00.5 cm, 2.0-2.5 cm, 5.0-5.5 cm, and 25.0-25.5 cm) were highly similar but were different from those collected at deeper depths (depths 50-50.5 cm and 84.0-84.5 cm). The deeper sediments present a different community structure with a markedly lower diversity than the shallower depths. Analysis of positive hybridization signals also revealed presence of genes common to all samples. The majority of these genes were similar to those retrieved from various environments (i.e. soils, groundwater, river water, strotomites, marine sediments, and estuarine sediments). Parallel coordinate display showed that the most dominant functional guilds are those that are involved in nitrogen cycling. Our results also indicated that this technology has potential as a tool in revealing a comprehensive "snapshot" of the functional gene composition in marine sediments, although more work is needed to understand the biological meaning of each detectable hybridization signal. PMID- 17285944 TI - Reduction on the anaerobic biological activity inhibition caused by heavy metals and sulphates in effluents through chemical precipitation with soda and lime. AB - The School of Chemistry Environmental Technology Laboratory generates 43.4 1 of effluent with low pH (0.7) and high contents of COD (1908 mgO2 l(-1)), phenol (132.1 mg l(-1)), sulfate (36700 mg l(-1)) and heavy metals (28.2 mg Hg l(-1); 82.1 mg Cr(total) l(-1); 30.8 mg Cu l(-1); 57.4 mg Fe(total) l(-1); 16.2 mg Al l( 1)) weekly. These data show that this effluent presents high toxicity for biological treatment, with a physical-chemical step being necessary before a biological step. Preliminary studies showed that the most toxic constituents of the effluent were sulfate, phenol and total chromium. In this work, a chemical precipitation step with sodium hydroxide or lime was evaluated for the toxicity reduction on anaerobic microbial consortium. These experiments were carried out with increasing concentrations of alkalis in the effluent in order to obtain pH initial values of 8-12. Similar results were obtained for COD (15-28%), turbidity (95-98%), phenol (13-24%) and total chromium (99.8-99.9%) removals in each condition studied with soda or lime. Sulfate was only removed by precipitation with lime, obtaining reductions from 84 to 88%. The toxicity on the anaerobic sludge was studied employing specific methanogenic activity (SMA) analysis of raw and treated effluent (after chemical precipitation step). The SMA experiments showed that chemical precipitation at pH 8 reduces the toxic effect of the effluent on anaerobic microbial consortium three times (with soda) and thirteen times (with lime). These results indicate that precipitation with lime is more efficient at toxicity removal, however the produced sludge volume is around two times higher than that produced with soda. PMID- 17285945 TI - Development of an integrated enzymatic treatment system for phenolic waste streams. AB - An integrated enzymatic treatment system, which includes Coprinus cinereus peroxidase (CIP) production, processing, and usage in batch or plug flow reactors, is being developed to remove phenolic compounds from the aqueous waste streams. CIP production at bench scale yielded a maximum growth medium activity of approximately 60 U CIP ml(-1). A CIP enzyme solution was prepared for use in treatment by successive filtration steps. This yielded a 4.5-fold increase in enzyme activity, with 87% enzyme activity recovery, and 83% reduction in the solution's Chemical Oxygen Demand. The purity of CIP was observed to have no effect on the ability of the enzyme to remove phenol from the aqueous solutions within the range of enzyme solution purities tested. Contrary to observations reported for phenol removal from buffered solutions, the addition of polyethylene glycol to non-buffered reaction solutions had no positive effect on the phenol removal accomplished at pH 7 in these experiments. The efficiency of enzyme use in a plug flow reactor was improved by step additions of CIP and H2O2. PMID- 17285946 TI - Article updates mortality rates among chemical workers. PMID- 17285947 TI - Partial breast irradiation: rationale and early results. AB - The purpose of this study is to introduce the concept of partial breast irradiation in the management of early stage breast cancer, and describe the early experience at treating patients at Schiffler Cancer Center at Wheeling Hospital in Wheeling, W.Va., with this new technology. A prospective analysis of the first 25 patients treated with breast brachytherapy, with detailed patient and tumor characteristics, will serve as a reference for further investigation into this technique. Results from this early experience will provide information that will further establish this technology as a feasible and appropriate treatment option for well-selected breast cancer patients. PMID- 17285948 TI - Isolated cerebellar metastasis in a patient with organ-confined, lymph node negative bladder cancer. AB - The majority of bladder cancer patients who develop brain metastasis have widely disseminated disease. Isolated cerebellar metastasis in patients with transional cell carcinoma (TCC) of the bladder is a rare event. We present the case of a patient with organ-confined bladder cancer who developed isolated cerebellar metastasis. PMID- 17285949 TI - Intrathecal morphine therapy related granulomas: two case reports. AB - Intrathecal morphine infusions have historically been used in patients with short life expectancies. More recently, patients with pain from a benign source have benefited from this therapy. While use in this population has been well documented and found to be relatively safe, new complications are being encountered secondary to the patients' longer life spans. The development of granulomatous masses from catheter use in intrathecal morphine therapy is an uncommon, but potentially serious problem. At West Virginia University Hospital, we have implanted more than 700 intrathecal drug delivery systems (IT-DDS) since 1989, and have encountered two cases of granulomatous masses developing at the tip of the intrathecal catheter. This report describes these illustrative cases and provides a review of the literature. PMID- 17285950 TI - Infantile botulism: a case report. AB - Although rare, botulism should be a consideration in the differential diagnosis of hypotonia in children. The pattern of clinical presentation and physical examination should raise the suspicion to make the appropriate diagnosis. Prompt clinical diagnosis and immediate appropriate treatment reduce morbidity and/or mortality in this disease. PMID- 17285951 TI - A culture of optimism or a plague of fatalism. PMID- 17285952 TI - Silent PPOs. PMID- 17285953 TI - TM failed to differentiate between concierge and direct fee-for-service practices. PMID- 17285954 TI - Important first chance. PMID- 17285955 TI - Are you withering or flourishing?--Part I. PMID- 17285956 TI - Marked bilateral parotid enlargement in metabolic syndrome: a case report and review of the literature. AB - Bilateral non inflammatory salivary gland enlargement (sialadenosis) is seen with a diverse number of diseases. It is commonly recognized in alcoholism, anorexia and bulimia nervosa and HIV infections. The association between diabetes mellitus and sialadenosis has been reported rarely in the last three decades. We report a patient with sialadenosis in association with metabolic syndrome. We discuss the clinical implications of this novel association including possible regression of salivary gland enlargement with intensive glycemic and lipid control. PMID- 17285958 TI - Weighing the decision to become a bariatric center of excellence. PMID- 17285957 TI - Gibson County health in 1834. PMID- 17285959 TI - CMS revises rules on H&P and more. PMID- 17285960 TI - Models for governance of the OR. PMID- 17285962 TI - Improving the OR's medication safety. PMID- 17285961 TI - Simulation labs aid OR staff education. PMID- 17285963 TI - JCAHO survey: being ready every day. PMID- 17285964 TI - Financial benchmarking for your ASC. PMID- 17285965 TI - [Endoscopic transnasal surgery for anterior skull base lesions]. AB - OBJECTIVE: To investigate the feasibility and subject range of endoscopic transnasal surgery for anterior skull base lesions. METHOD: Six patients affected with anterior skull base diseases in recent years were studied. The lesions were included 3 cases of cen encephalocele, 2 of cerebrospinal rhinorrhea and one of left retrobulbar tumor. All 6 patients received endoscopic transnasal surgery under general anesthesia. RESULT: All patients had accepted successful one-stage surgeries without any complications. CONCLUSION: Endoscopic transnasal surgery for some anterior skull base lesions has the advantages of tiny injuring, quick recovery and few complications. But surgical indications must be controlled seriously. The operator must hold skillful anatomic intelligence, surgical technique and experiences as well as advanced surgical apparatuses. PMID- 17285966 TI - [The effect of TNF-alpha & IL-8 in the pathogenesis of allergic rhinitis]. AB - OBJECTIVE: To survey the effects of TNF-alpha and IL-8 in the pathogenesis of allergic rhinitis. METHOD: The serum levels of TNF-alpha and IL-8 in 102 cases of seasonal or non-seasonal allergic rhinitis were detected pre and post specific immunotherapy (SIT), and the results were statistically analyzed. RESULT: The levels of TNF-alpha and IL-8 in experiment group were significant higher than that in the health control. And the levels of TNF-alpha and IL-8 significantly decreased post SIT in the experiment group. CONCLUSION: TNF-alpha and IL-8 play important roles in the pathogenesis of allergic rhinitis. PMID- 17285967 TI - [The diagnosis and treatment of cerebrospinal rhinorrhea caused by transsphenoidal cephalocele through transnasal endoscopic surgery]. AB - OBJECTIVE: To inquire into the feasibility of transnasal endoscopic surgery for the diagnosis and treatment of cerebrospinal rhinorrhea caused by transsphenoidal meningo encephalocele. METHOD: Three cases of cerebrospinal rhinorrhea caused by transsphenoidal meningo encephaloceles were managed by transnasal endoscopic surgery. Different repair materials such as muscle, fascia, artificial dural material were applied into the defect site. RESULT: All cases were successful treated, 1 of them complicated with meningitis, the others were cured without any complication. One reoccurred after 6 months and was successful repaired after second surgery during 1-3 year follow-up. CONCLUSION: The treatment of transnasal endoscopic surgery for cerebrospinal rhinorrhea caused by transsphenoidal cephalocele is a feasible, mini-wound and safe approach. PMID- 17285968 TI - [A clinic study on treatment of chronic frontal sinusitis with endoscopic surgery and permanent implantation of a place holder]. AB - OBJECTIVE: To investigate the characteristics of chronic frontal sinusitis and to improve the clinical therapeutic efficacy. METHOD: Sixty-eight patients (130 sides) who underwent endoscopic frontal sinus surgery in our department were randomly divided into three groups: Group 1 included 23 patients (43 operations) underwent endonasal sinus surgery with the frontal sinus opened and drained by two pipes of silicone for 6 months. Group 2 included 24 patients (45 operations) treated as group 1 but added injection of beclomethasone (approximately 1 cc, 94 mcg/100 microliters). Group 3 included 21 patients (42 operations) with only frontal sinus opened. RESULT: After an average follow-up of 18 months, the cure rate in group 1, group 2 and group 3 was 93%, 93% and 71% respectively. CONCLUSION: The ultimate success or failure of frontal sinus surgical procedures, whether they are endonasal or external, depends on the restenosis of the frontal sinus outflow tract or neo-ostium postoperatively. Long-term stenting for a period of several months will significantly reduce the possibility of restenosis. We recommend that this type of management be considered in difficult revision cases and before performing an external operation. PMID- 17285969 TI - [Acute frontal sinusitis accompanied with extra-dural abscess (a case reported with literature reviewed)]. AB - OBJECTIVE: To investigate the clinical characteristics of acute frontal sinusitis accompanied with extra-dural abscess. METHOD: A case of acute frontal sinusitis accompanied with extra-dural abscess diagnosed by CT was analyzed, and the relative literatures were reviewed. RESULT: Headache, high fever and failure to antibiotic therapy were the main three clinical characteristics. CONCLUSION: It is the most important thing to drainage the abscess except for antibiotic therapy for acute frontal sinusitis accompanied with extra-dural abscess. Antibiotic therapy cannot substitute for surgery. PMID- 17285970 TI - [Operation of chronic sphenoid sinusitis with endoscopic sinus surgery]. AB - OBJECTIVE: To evaluate the method and treatment effect of endoscopic sinus surgery for chronic sphenoid sinusitis. METHOD: Fifty cases, 84 sides of chronic sphenoid sinusitis patients were treated with endoscopic sinus surgery. RESULT: In the follow-up of 6-12 months, 61 sides (72.62%) were cured; 13 sides (15.48%) were mended; 10 sides (11.90%) were ineffective; 74 sides were effective, the effectiveness rate were 88.10%. CONCLUSION: Treatment with endoscopic sinus surgery is a safe, effective method with little pain for chronic sphenoid sinusitis. PMID- 17285971 TI - [The clinical application of Ephedrine Test in acoustic rhinometry]. AB - OBJECTIVE: To discuss the clinical application of Ephedrine Test in acoustic rhinometry, we studied the method of quantitative evaluation for nasal mucosal state and discriminated the objective parameters between simple rhinitis and hypertrophic rhinitis. METHOD: Nasal cavity of volunteers from normal, simple and hypertrophic rhinitis patients were tested by acoustic rhinometry, the Nasal Airway Resistance (NAR), Nasal Cavity Volume (NCV), Nasal Minimal Cross-section Area (NMCA) and Distance of the minimal Cross-sectional Area from the Nostril (DCAN), their difference value and variational rate of pre or post Ephedrine Test were analyzed and compared. RESULT: The paired-samples data of pre-post Nasal Ephedrine Test showed that NAR, NCV, NMCA and DCAN had extremely significant difference (P < 0.01). NCV and NMCA had increased, NAR had reduced and DCAN had "shifted forward" after Ephedrine Test. All the parameters had extremely difference (P < 0.01) among multi-group at pre or post Ephedrine Test. Only NCV had significant difference before Ephedrine Test (P < 0.05). However, after Ephedrine Test, all of the parameters (include difference value and variational rate) had significant difference (P < 0.05 or P < 0.01) between simple and hypertrophic rhinitis patients. Compared with volunteers of normal nasal cavity: all of the parameters (include difference value and variational rate) had significant difference (P < 0.05 or P < 0.01) in simple rhinitis patients, but some of the parameters of their difference and variational rate had not significant in hypertrophic rhinitis patients. CONCLUSION: The acoustic rhinometry test can objectively estimate the state of nasal mucosal and get more information combine with Ephedrine Test. It can expand the clinical application of acoustic rhinometry and is worth while recommending. PMID- 17285972 TI - [Expression of PCNA, VEGF and bFGF in endothelial cells of juvenile nasopharyngeal angiofibroma]. AB - OBJECTIVE: To investigate the nature of juvenile nasopharyngeal angiofibroma (JNA). METHOD: The difference of PCNA, VEGF and bFGF expression between hemangioma and vascular malformation in children and infant was applied to this study. 25 cases of JNA,10 cases of hemangioma and 11 cases of vascular malformation were studied respectively by immunohistochemical methods. RESULT: The PCNA and VEGF expression in the endothelial cells of JNA were negative, the PCNA and VEGF expression in the endothelial cells of haemangioma were positive, the PCNA and VEGF expression in the endothelial cells of vascular malformation were negative, there were extraordinary significant difference between the group of JNA and haemangioma (P < 0.01). There were no significant difference between the group of JNA and vascular malformation ( P > 0.05). The bFGF expression in the endothelial cells of JNA was positive, the bFGF expression in the endothelial cells of haemangioma was positive, the bFGF expression in the endothelial cells of vascular malformation was negative, there were no significant difference between the group of JNA and haemangioma (P > 0.05). There were extraordinary significant difference between the group of JNA and vascular malformation (P < 0.01). CONCLUSION: The nature of JNA could be a congenital proliferative vascular malformation. PMID- 17285973 TI - [The use of Mandarin hearing in noise test in non-Mandarin speakers]. AB - OBJECTIVE: To test non-mandarin native-speaker of normal hearing with MHINT. METHOD: Eighty-two non-native Mandarin speakers with normal hearing were included. The test were done under four test conditions by HINT for Windows V6.1. The results were compared between non-mandarin native-speakers' with mandarin native-speakers'. The results were analyzed statistically. RESULT: Three hundred and twenty-eight results of the subjects were gained. There was evident significantly difference between mandarin and non-mandarin native speakers (P < 0.01), and between non-mandarin native speakers with high educational level and low educational level ( P < 0.01), but there was no difference when compared with their age, time of use Mandarin in the results (P > 0.05). CONCLUSION: Non mandarin native-speakers' results are lower than mandarin native-speakers'. The primary factor affect MHINT results are native language and educational experiences. PMID- 17285974 TI - [Study on the expression of angiogenesis and spontaneous apoptosis and their relevance in laryngeal squamous cell carcinoma]. AB - OBJECTIVE: To investigate the relationship among angiogenesis, spontaneous apoptosis and clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC). METHOD: The intratumor microvessel density (IMVD), apoptotic index (AI) and vascular endothelial growth factor (VEGF) expression were detected by immunohistochemistry SABC and terminal uridine deoxynucleotidyl transferase mediated nick end labeling(TUNEL) methods in 34 LSCC patients. RESULT: The average IMVD was (21.50 +/- 8.87), and median of AI was 1.15%. The average IMVD in positive and negative cervical lymphatic metastasis was (26.33 +/- 9.70) and (17.68 +/- 6.06) respectively, and the IMVD with positive lymphatic metastasis tumors was statistical significantly higher than those with negative cervical lymphatic metastasis tumors (P < 0.01). The average IMVD had statistical difference in histological grading (P < 0.01), and analysis by one to one, the average IMVD had statistical difference between high and median grading. Expression of VEGF had a significantly positive correlation with IMVD (r = 0.51, P < 0.01). Statistical analysis revealed a significantly inverse correlation between AI and IMVD (r = -0.53, P < 0.01). We failed to find the statistical difference between IMVD and tumor T-stage in LSCC. CONCLUSION: IMVD may be an important indicator to predict cervical lymphatic metastasis in LSCC. VEGF might be an important angiogenic factor, and could promote tumor angiogenesis in LSCC. Tumor angiogenesis might contribute to tumor malignant progression by inhibiting spontaneous apoptosis in LSCC. PMID- 17285975 TI - [Sleep architecture changes in children with adenoidal hypertrophy]. AB - OBJECTIVE: Adenoidal hypertrophy in children is associated with obstructive manifestations like mouth breathing, snoring, night cough. However, the sleep architecture is poorly defined in children with AH, which is this studies for. METHOD: A computer-assistant diagnostic system was used for polysomnography (PSG) recording. Sleep was scored manually according to the standard set by Rechtschaffen. 47 children with adenotonsillar hypertrophy (AH) were defined by PSG and compared with normal children PSG results. RESULT: (1) Compared with normal children, AH group had increased stage I: (15. 4 +/- 9.3)% vs (7.9 +/- 6.8)% (P < 0.01) and decreased stage II: (41.8 +/- 9.7)% vs (46.7 +/- 7.6)% (P < 0.01); increased Delta (26.2 +/- 10.6)% vs (23.3 +/- 8.7) % (P > 0.05); obviously decreased in REM: (7.7 +/- 4.9)% vs (27.3 +/- 5.6)% (P < 0.01); NREM (83.33%) was increasingly; (2) AH group had increased Arousal Index(ARI) 32.8 +/- 26.03 vs 18.3 +/- 12.2 (P < 0.05); (3) The latent period of REM was (157.1 +/- 71.4) min and about two times long as normal children. CONCLUSION: Sleep architecture is abnormal in children with AH. Frequent electroencephalogram arousals from sleep may result in significant sleep fragmentation,but the deep sleep is sufficient. Further studies are needed to determine whether abnormalities in sleep architecture contribute to quality of life. PMID- 17285976 TI - [Determination and the diversity characteristic of the cytokine levels in the supernatants of spleen cell cultures of experimental allergic rhinitis mice]. AB - OBJECTIVE: To investigate the cytokine level in the supernatants of spleen cell stimulated with different stimulus of allergic rhinitis model at different time, compared the effect of the two stimulus to the cytokine, and its secrete status. METHOD: We sensitized and challenged the BALB/c mice with ovalbumin (OVA), in the control group normal sodium instead of OVA was used. After the last challenge we cultured the spleen mononuclear cell (SMNC) and stimulated with OVA or concanavalin A (ConA), then got the supernatants of the SMNC cultures at 24 h, 48 h and 72 h respectively to measure the concentration of cytokine IL-4, IL-5 and IFN-gamma. RESULT: Production of IL-4, IL-5 and IFN-gamma by ConA-stimulated SMNC from sensitized mice increased significantly (P < 0.05); the concentration of IL 4 and IL-5 by OVA-stimulated SMNC from sensitized mice also increased, inversely the production of IFN-gamma resulted suppression. The level of IL-4 was increased obviously in 72 hours, IL-5 and IFN-gamma were increased significantly in 48 hours, and slow down from 48 to 72 hours. CONCLUSION: The T cells of the experimental allergic rhinitis mice were generally activated. Production of cytokines from Th2 cells by OVA or ConA increased significantly, but Th1 cells and its cytokines were suppressed. The result was more obvious in the ConA stimulated group. The levels of cytokines increased persistently within 72 hours. PMID- 17285977 TI - [Phytochemical and pharmacological research progress in Tussilago farfara]. AB - Tussilago farfara contained the chemical constitutents including terpenes, flavonoids, and alkanoids. It has been used for the relief of coughs and as an expectorant, blood pressure raiser, platelet activating factor inhibitor and anti inflammatory agents. This paper reviewed the phytochemical and pharmacological research progress in T. farfara, including the chemical ingredients, the pharmaceutical activities and the security evaluation aiming at its toxicity. The problems at present and the reseach direction for the future on T. farfara have been put forward. PMID- 17285978 TI - [Advances in residues analysis of pesticide in Chinese herbal medicine and new technological development]. AB - The current methods to prepare and determine pesticide residues in Chinese herbal medicine were summarized in this paper. In addition,the new techniques to prepare and determine pesticide residues used in recent years was reviewed, which included solid-phase micro-extraction (SPME) , supercritical fluid extraction ( SFE) , accelerated solvent extraction (ASE) , immune affinity chromatography (IAC), supercritical fluid chromatography (SFC), column switching high performance liquid chromatography (CSHPLC), high performance liquid chromatography/mass spectrometry (HPLC/MS), capillary electrophoresis (CE) and capillary zone electrophoresis (CZE) , and immune analysis (IA), etc. To sum up, these would bring a great progress in analysis of the pesticide residues in Chinese herbal medicine, and make it more rapidly, accurately and normatively. PMID- 17285979 TI - [Studies on chromosome numbers of Salvia miltiorrhiza, S. flava and S. evansiana]. AB - OBJECTIVE: To study the numbers of chromosome in Chinese herb Salvia miltiorrhiza from 7 provinces in China, and S. flava as well as S. evansiana from Yunnan province in China. METHOD: The young root was treated with the mixture of ice and water for 24 h, fixed with Carony's fixative for 6-12 h. After differentiating for 10-12 min with 1 mol x L(-1) hydrochloric acid at 60 'C and staining with carbol fuchsin,the section was observed under microscope. RESULT: Chromosome numbers of S. miltiorrhiza and S.flava were 2n = 2x = 16. The numbers of S. evansiana were 2n = 4x = 32. The basic numbers of the chromosomes were x = 8. And tetraploids were observed in S. miltiorrhiza from Sichuan provices and Shandong provices. CONCLUSION: The basic number of the chromosomes are x = 8. The chromosome numbers of S. miltiorrhiza, S.flava and S. evansiana are 16,16 and 32 respectively. As the chromosomes are the small or micro-small ones, it is difficult to use them for karyotype. PMID- 17285980 TI - [Tissue structure observation of internal organs and skin of Whitmania pigra]. AB - OBJECTIVE: Through observation of the tissue structures of internal organs and skin of Whitmania pigra, to provide basic method for identification of W. pigra and research of its physiological functions. METHOD: This experiment adopted the W. pigras as the material and carried on dissection observing,and W. pigra's cavity, swallow, esophagus, crop, bowel, rectum, parasomal sac stomach, testicle, seminal vesicle, vasa deferentia duct, ejaculatory ball, prostate gland and skin was observed by the method of the paraffin organization slice and microphotography. RESULT AND CONCLUSION: The structures and functions of the skin and the organ of the digestive and reproductive system, as well as the types and distributions of the mucous cells were acquired,which provided abasis for further study on the living behaviour, propagating behaviour and breeding environment of W. pigra. PMID- 17285981 TI - [Hairy roots induction of Phellodendron chinense and production of its active constituents]. AB - OBJECTIVE: To introduce the hairy roots of Phellodendron chinense and determine the content of its active constituents. METHOD: Transformed hairy roots of P. chinense were obtained by the transformation of Agrobacterium rhizogenes A4, R1600, ATCC15834 and R1000. RESULT AND CONCLUSION: It was clearly demonstrated that T-DNA of A. rhizogenes Ri plasmid was integrated into the cells of hairy roots by PCR. The content of berberine hydrochlodride, which was determined by HPLC, was higher in hairy roots than that in the axenic plantet and callus. PMID- 17285982 TI - [Effects of carbon source and nitrogen source on callus growth and flavonoid content in Glycyrrhiza uralensis]. AB - OBJECTIVE: To study the effects of carbon source and nitrogen source on callus growth, and flavonoid content in Glycyrrhiza uralensis. METHOD: Induction and culture of callus were conducted in the media of different concentrations of sucrose, and fructose and ratio of NH4+/NO3- ,and flavonoid content was measured by HPLC. RESULT: The results showed that fructose was superior to sucrose for callus growth and flavonoid formation, and the optimum concentration was 2%. The flavonoids content was 2 times higher than that of sucrose as carbon sources. In the range of 2% -6% of fructose concentration, the flavonoid content was decreased along with the concentration of fructose, but the licochalcone was increased 5-fold. The highest flavonoid content of 151.47 microg x g(-1) was obtained when the ratio of NH4+/NO3- in the medium was 1/2. NH; inhibited the callus growth and flavonoid formation of G. uralensis. CONCLUSION: Fructose as carbon source was superior to sucrose for callus growth and flavonoid formation, and NO3- was favorable to the callus growth and flavonoids accumulation. PMID- 17285983 TI - [Study on extraction process of polysaccharide from Sargassum fusiforme by enzymatic treatment]. AB - OBJECTIVE: To investigate the optimal extraction process of polysaccharides from S. fusiforme by enzymatic treatment. METHOD: The optimum extraction conditions were obtained by the experiment with the orthogonal design. The content of polysaccharides of S. fusiforme was determined by spectraphotometry. RESULT: The amount of enzyme and temperature significantly affected total polysaccharides of S. fusiforme. CONCLUSION: The optimum extraction conditions include the addition of 1. 2 x 10 (4) U x 100 g(-1) enzyme into water at pH 4. 5, and the subsequent treatment for 10 min while the temperature is maintained at 45 degrees C. PMID- 17285984 TI - [Formulation and process optimization of formula Qiqi pellets prepared by extrusion-spheronization]. AB - OBJECTIVE: To prepare traditional Chinese medicine formula Qiqi pellets by extrusion-spheronization and study the optimal formulation and process. METHOD: Qiqi pellets were prepared by a new style extrusion-spheronization equipment, the optimal formulation and process was obtained by the studies of influenitial factors and L9 (3(4)) orthogonal design, the micromeritic properties and product yield of pellets were determined. RESULT: The formula Qiqi pellets prepared by extrusion-spheronization were all spheral with smooth surface; the product yield was high. CONCLUSION: Extrusion-spheronization was suitable to produce Chinese Herbal Medicine pellets. The preparation process was simple and feasible; The quality of the prepared pellets was excellent. It was worth further study. PMID- 17285985 TI - [Analysis of dencichine by HPLC with pre-column derivatization]. AB - OBJECTIVE: To establish a reversed-phase high performance liquid chromatorgraphy (RP-HPLC) method for detecting the dencichine in Panax notoginseng extracts and drug preparations. METHOD: Dencichine was extracted with the borate buffer (pH 9. 18) and the clear supernatant was used for the derivatization. Pre-column derivatization was performed using 9-fluorenylmethyl chloroformate (FMOC) to form derivatives. The mobile phase consisted of methanol and 0. 05 mol x L( -1) NaH2 PO4 (48: 52) (pH adjusted to 7.4 with NaOH solution) in a flow rate of 1.0 mL m min(-1). The ultraviolet (UV) detection wavelength was set at 262 nm. RESULT: The linearity was demonstrated over a wide range of concentration from 1.76 mg L(-1) to 352 mg x L(-1) for dencichine. The detection limit was determined to be 60 microg x L(-1). The derivative was stable and the derivatization agent did not influence the measurement of dencichine. The average recovery rate was 95. 3% and the relative standard derivation (RSD) was 1. 7%. The method was used to determine dencichine in different P. notoginseng extracts and drug preparations. CONCLUSION: This method is simple, fast and sensitive, suitable for determining the dencichine in P. notoginseng extracts and drug preparations as well as for the study of the dencichine metabolism in vivo. PMID- 17285986 TI - [Studies on chemical constituents of Acroptilon repens]. AB - OBJECTIVE: To investigate the chemical constituents of Acroptilon repens. METHOD: The ethanol extract of A. repens was isolated and purified by means of chromatography. These compounds were identified by their spectral data. RESULT: 11 compounds were isolated and identified as 2alpha, 9beta-dihydroxy dehydrocostus lactone (1) , cynaropicrin (2) , apigenin (3) , stigmasterol (4) , 4' -hydroxywogonin (5) , ethyl caffeate (6) , p-methoxy-cinnamic acid (7) , luteolin (8) , daucosterol (9) , apigenin-7-O-beta-D-glucoside (10) , syringin (11). CONCLUSION: Compounds 5-11 were isolated from A. repens for the first time. Compound 1 is new compounds. PMID- 17285988 TI - [Triterpenes from herb of Potentilla chinesis]. AB - OBJECTIVE: To study the chemical constituents of Potentilla chinesis and their anticancer activities. METHOD: Chemical constituents were isolated by repeated column chromatography (Toyopearl HW-40C and preparative HPLC). The structures were elucidated on the basis of spectral data analysis. The isolated compounds were screened with two anticancer models. RESULT: Fifteen triterpenes, alpha amyrin (1) , beta-amyrin (2) , ursolic acid (3) , corosolic acid (4), euscaphic acid (5) , pomolic acid (6) , tormentic acid (7), 2alpha, 3alpha-dihydroxyurs-12 en-28-oic acid (8), 2beta, 3beta, 19alpha-trihydroxyurs-12-en-28-oic acid (9), asiatic acid (10) , 24-hydroxy tormentic acid (11) , myrianthic acid (12), oleanolic acid (13), maslinic acid (14) and 2alpha, 3alpha-dihydroxyolean-12-en 28-oic acid (15) , were isolated from P. chinesis. CONCLUSION: Compounds 1, 2, 4 15 were isolated from the plant for the first time. Compounds 4, 8 - 10, 12, 14 and 15 show anticancer activities. Compounds 4, 9 show strong activities. PMID- 17285987 TI - [Studies on constituents in herb of Senecio scandens]. AB - OBJECTIVE: To isolate the constituents of Senecio scandens and determine their structures. METHOD: Componds were isolated and purified by silica gel column chromatography and the structures were identified by spectroscopic methods. RESULT: Nine compounds were isolated as lupenone (1) , oleanane (2) , beta sitosterol (3) , daucosterol (4) , adonifoline (5) , phydroxy benzeneacetic acid (6) , 2-(1,4-dihydroxy-cyclohexanyl) -acetic acid (7), hyperoside (8), linarin (9). CONCLUSION: These compounds were obtained from S. scandens for the first time except 4 and 6. PMID- 17285989 TI - [Cystic degeneration in liver injury induced by CCl4 in SD rats]. AB - OBJECTIVE: To explore the hepatic injury induced by CCl4in SD rat. METHOD: 40 SD rats were allocated to male and female group, consisting of 20 animals/sex/group. SD rats were given at 2 mL x kg(-1) of 10% CCl4 through celiac injection per 3 day for 12 days. All rats were killed by anaesthesia of ethyl ether and bleeding through abdominal aorta at 12th day. Liver tissue was fixed in 10% neutral formalin, embedded in paraffin, cut at a nominal thickness of 3 microm, stained with hematoxylin and eosin ( H&E) , evaluated at by microscopic examination. RESULT: 19 cases with local necrosis, 8 cases with fatty degeneration, 9 cases with cystic degeneration and 2 cases with fibrosis were seen in group male. 20 cases with local necrosis, 9 cases with fatty cases degeneration, 1 case with cystic degeneration and 1 case with fibrosis were seen in group female. The incidence of cystic degeneration in male group was found significantly higher than that in female group (P < 0. 05) , but the incidence of other lesions was no significant difference between male and female group. CONCLUSION: CCl4 induces local necrosis , fatty degeneration, fibrosis and cystic degeneration in SD rat. The incidences of local necrosis , fatty degeneration and fibrosis were no significantly difference between male and female rat, but the incidence of cystic degeneration in male rats was significant higher than that in female rats. PMID- 17285990 TI - [Study on transdifferentiation of renal tubular cells in rat chronic renal interstitial fibrosis induced by Radix Aristolochiae Fangchi Extract]. AB - OBJECTIVE: To investigate the relationship between renal tubular cells transdifferentiation and chronic renal interstitial fibrosis induced by Fangchi Extract in rat. METHOD: The chronic renal interstitial fibrosis rat model was made by giving Radix Aristolochiae Fangchi extract (RAFE) and aristolichic acid (AA) respectively to rats through infusing stomach about 22 weeks discontinuously. Through immunnal histochemistry methods, investigating the expression of symbol proteins: Cytokine( CK) , alpha-Smooth muscle actin ( alpha SMA) and Vimentin, and also the important fibrosis inducing factor-Transforming growth factor-beta (TGF-beta1 )on renal tubular cells. RESULT: In RAFE and AA Groups, the expression of CK on renal tubular cells is declined comparing with the Control Group, and the enhanced expression of alpha-SMA and Vimentin can be observed on tubular cells. The expression of TGF-beta1 on renal tubular cells stronglhy increased, too. CONCLUSION: Part of the renal tubular cells was transdifferentiated into myofibroblasts. Renal tubular cells may participate the occurance of chronic renal interstitial fibrosis, TGF-beta1 may accelerate the transdifferentiation of tubular cells. PMID- 17285992 TI - [Effect of Fuzheng Jiangan formula on liver fibrosis induced by albumin in rats]. AB - OBJECTIVE: To observe the effect of Fuzheng Jiangan formula( FZJGF) on liver fibrosis using immune induced liver fibrosis rat model. METHOD: The rat models with immunity liver fibrosis were induced by the human serum albumin. Rats were treated with normal saline, FZJGF (9. 85,39. 4 g x kg(-1) , two dosage groups) and Colchicine (0. 000 1 g . kg(-1) ). The activities of ALT, AST, contents of ALB and TP, and A/G, The contents of Laminin (LN), Hyaluronic acid (HA) and collagen type IV (IV-C) in rat serum were measured by radioimmunoassay method. The level of hydroxyproline (Hyp) in liver was detected by chemistry method. The pathological changes of liver tissue were observed by HE and Von-Gieson staining. RESULT: FZJGF could significant decrease the serum activities of ALT and AST, and increase the levels of TP,Alb and ratio A/G. The levels of LN, HA and IV-C were decreased significantly after the treatment using FZJGF. The pathological improvements were observed. FZJGF could markedly alleviate the deposition of collageneous fiber, and reduce the liver pseudoluboli and the fibrosis scores in the liver tissue compared with model group. CONCLUSION: FZJGF can inhibit formation and development of rat hepatic fibrosis induced by the human serum albumin. PMID- 17285991 TI - [Anti-atherosclerotic effects of divided functional recipes of Dahang Zhechong pill in rabbits]. AB - OBJECTIVE: To study the effects of the divided functional recipes of Dahuang Zhechong pill( DHZCP) on atherosclerosis in rabbits. METHOD: The atherosclerotic model was established by the combination of hypercholesterol feeding and immune injured endothelium in rabbits. Male New Zealand rabbits were randomly divided into nine groups: normal group, model group, Danshen group (0. 5 g x kg(-1) ), the low-dose(0. 5 g x kg(-1) ) and high-dose( 1.0 g - kg(-1) ) groups of the first divided recipe, the low-dose(0. 75 g x kg-' ) and high-dose(1. 5 g x kg( 1)) groups of the second divided recipe, the low-dose(0. 8 g x kg(-1) ) and high dose( 1.6 g x kg(-1) ) groups of the third divided recipe. The effects of the divided functional recipes of DHZCP were observed in macropathology, histopathology and ultrastructure. Image analyzing system was used to determine atherosclerotic plaque area, intima thickness(IT) and intima-media thickness(IMT) in rabbit aorta. RESULT: The divided functional recipes of DHZCP could significantly decreased the deposit of lipid and the atherosclerotic plaque area in aorta intima, relieve the histopathological changes of atherosclerosis, and inhibited the proliferation of vascular smooth muscle cells and collagen to reduce pachynsis of vascular intima. The divided functional recipes of DHZCP also reduced IT, IMT and IT/MT and reversed the contractive vascular remodeling. CONCLUSION: The divided functional recipes of DHZCP produce the different anti atherosclerotic action, among which the first divided functional recipe exhibits more effective action. PMID- 17285993 TI - [Repair alveolar cleft bone defects with bone marrow stromal cells]. AB - OBJECTIVE: To explore the feasibility of repairing alveolar cleft bone defects with bone marrow stromal cells. METHODS: Total 7 patients of alveolar cleft were included in this study. The hBMSCs were isolated by percoll gradient centrifugation from patient's bone marrow aspirated from iliac crest. The hBMSCs were cultured in vitro and induced to become osteogenic cells in the DMEM medium containing 10% self-serum, beta-glycerophosphate (10 nmol/L) dexamethasone (10( 8) mol/L) , L-2-ascorbic acid(50 micromol/L), and 1, 25 (OH)2 VD3 (10 nmol/L). Induced hBMSCs of passage 3 were harvested and seeded onto partly demineralized allogenic bone matrix (pDBM) to form a cell-scaffold construct and in vitro co culture for 1 week. The defects were repaired with the cell-scaffold construct. All cases were followed up for 3, 6 months post-operation as short-term evaluation and 1 to 3 years post-operation as long-term evaluation by three dimensional computerized tomography (3D-CT) and clinical examination. RESULTS: 3D CT demonstrated that engineered bone was formed in 3 months post-operation. Additionally, formed bone maintained stable up to 1 - 3 years without absorption. CONCLUSIONS: Engineered bone can be used to repair clinical alveolar cleft bone defects. PMID- 17285994 TI - [The effect of artificial bone implantation in cleft palate on the development of maxilla]. AB - OBJECTIVE: To research the influence of palate bone implantation to the growth of maxilla in three dimensional direction. METHODS: 40 patients of congenital cleft palate type II with palate board damage were stochastically divide into the comparison group and bone planted group. In bone planted group, HA-Bone cement was used to repair palate tabular damage. All patients are 16 full year old, cephalometric radiograph and tooth cast model were measured and contrast analysis was applied. RESULTS: Planted bone group and the comparison group does not have the significance difference in both the maxilla length and maxilla hightness( P > 0.05); But there was significance difference in the width of post-part of the maxilla (P < 0.05). CONCLUSIONS: It could promote the growth of maxilla width in use of bone implantation, that advocated the bone repair in the sequence treatment process in cases of the hard palate bone damage. PMID- 17285995 TI - [Adaptive change of masseter muscle after the ostectomy of mandibular angle in rabbits]. AB - OBJECTIVE: To study the changes of masseter muscle after reducing the mandibular by measuring some relative index after ostectomy of the mandibular angle along arch line. METHODS: Left mandibular angle ostectomy was performed on New Zealand female rabbits aged three months. The right was not operated as control groups. Five rabbits were examined at the following intervals: 2, 4, 8, 12 and 24 weeks. RESULTS: There were remarkable decreases in the experimented masseter muscle masses and the same type muscle fiber areas compared with the control group (P < 0.05). As for the fiber types, a decrease in type I fibers and an increase in type II fibers were noticed on operative side masseters (P <0.05). Sarcomere lengths in the operative side muscles were significantly reduced and showed statistical significance during first 4 weeks (P < 0.05), but there was no difference between the operative group and the control group after 8 weeks (P > 0.05). CONCLUSIONS: The changes of masseter fibres show reconstruction of masseter muscle after mandibular angle ostectomy. PMID- 17285996 TI - [Expandable implants in immediate breast reconstruction]. AB - OBJECTIVE: To investigate the indications, surgical methods and esthetic results in patients undergoing immediate breast reconstruction with expandable implants. METHODS: From January 2002 to March 2006, immediate breast reconstructions were carried out with expandable implants following mastectomy in 30 breast cancer patients. Nipple-areola were preserved in 5 patients. RESULTS: Very satisfactory results were achieved. Minor complications were recorded in 3 patients, two with local skin necrosis, and another with partial necrosis of nipple-areola complex. CONCLUSIONS: The techniques provide better results for the patient who is not a candidate for simple implant reconstruction. These techniques also eliminate the need for a second major surgery to replace a temporary expander with a permanent implant in those patients needing soft tissue expansion. It is a simple procedure with advantages of no additional scarring, short time for convalescence. PMID- 17285997 TI - [In-operation adjusting in inferior pedicle technique reduction mammaplasty]. AB - OBJECTIVE: To overcome inflexible disadvantage in reduction mammaplasty design. METHODS: Preoperation, locating approximately new nipple position and redundant breast skin range. In operation, reshaping unfinished breast shape and locating new nipple-areola position finally in near elective position, breast is reduced using inferior pedicle technique. RESULTS: From August, 1995, 34 cases were performed using this method. After 3 - 18 months' follow-up, the result show that there isn't obvious complication, new breast shape is natural, nipple--areola sense exist. CONCLUSIONS: This design method is simple, flexible, operation is safe, effect is reliable. PMID- 17285998 TI - [The treatment for complications of polyacrylamide hydrogel injection for augmentation mammaplasty by dual-plane breast augmentation]. AB - OBJECTIVE: To search for the perfect therapy for the complications of breast augmentation by injecting polyacrylamide hydrogel. METHODS: 15 patients whose complications were severe after hydrogel injection were included in this study. Open suction and irrigation of cavity were performed in all patients and all received immediately dual-plane augmentation mammaplasty with silicon gel prostheses. RESULTS: 12 patient were followed up for 3 months to 1 year (mean 6.8 months) and no malposition or deformation occurred. 10 patients (20 breasts) had satisfactory results. The edges of the implant shell could be felt in 2 patients (3 breasts). 1 patient (1 breast) with breast firmness ranked Baker II . CONCLUSIONS: The dual-plane breast augmentation is a valuable technique to treat the complications of polyacrylamide hydrogel injection. PMID- 17285999 TI - [External ear reconstruction using expanded postauricular scar flap and Medpor framework]. AB - OBJECTIVE: To investigate the possibility of external ear reconstruction using expanded postauricular scar flap and Medpor framework in burn cases. METHODS: External ear reconstruction using expanded postauricular scar flap in combination with Medpor framework was performed in 17 cases whose ear had burn injury. RESULTS: Of the 17 cases, 15 cases achieved success; 2 cases experienced partial exposure of the framework due to inadequate wrapping of the subcutaneous fascia flap and later injury. The longest follow-up was three years, and the final result was satisfactory. CONCLUSIONS: External ear reconstruction using expanded postauricular scar flap in combination with Medpor framework is a reliable method for adult (over 25 years) who has ear defect from burn injury. PMID- 17286000 TI - [Template design of tissue flaps for covering auricular cage in one-stage total auricular reconstruction]. AB - OBJECTIVE: To study the template design of tissue flaps for covering auricular cage in order to acquire accurate and reliable design method. METHODS: By the theory of engineering drawing and three-dimensional measuring on CT image, three dimensional configuration of 40 auricular surfaces were expanded approximately, and the character of them was analysed for the template design. RESULTS: It is similar of the expanded graphs of auricular surface three dimensional configuration in healthy persons, and simplified template of tissue flaps is drawn based on the key points of the above graph. CONCLUSIONS: CT three dimensional measurement of auricular surface configuration can be used to design the template of tissue flaps for covering auricular cage, and can provide accurate and reliable template of tissue flaps for clinics. PMID- 17286001 TI - [Microsurgical tissue transfer for the reconstruction of hemifacial atrophy (Parry-Romberg syndrome)]. AB - OBJECTIVE: To reconstruct the soft tissue defect of the hemifacial with free anterolateral thigh fascioadipose flaps or scapular dermal-adiposal flap. METHODS: The free anterolateral thigh fascioadipose flaps based on the perforators of lateral circumflex femoral artery or scapular dermal-adiposal flap based on the circumflex scapular artery has been designed and reconstructed hemifacial atrophy with the donor artery and vein anastomosed to the facial artery and vein. RESULTS: Anterolateral thigh fascioadipose flaps were performed in 7 patients. Scapular dermal-adiposal flap was applied in 1 patient. All the flaps survived well and aesthetic appearance of reconstructed face achieved good result. CONCLUSIONS: The microsurgical tissue transfer, especially the free anterolateral thigh fascioadipose flap is a good and reliable choice for hemifacial reconstruction. PMID- 17286002 TI - [Microvascular anastomotic anterolateral thigh flaps for reconstruction of traumatic widespread defects of soft tissue in heel]. AB - OBJECTIVE: To explore the results of repairing widespread defects of traumatic soft tissue in heel by microvascular anastomotic anterolateral thigh flaps. METHODS: Twenty-six consecutive free anterolateral thigh flaps in 26 patients were transplanted for repairing widespread defects of traumatic soft tissue in heel from October 1997 to March 2005, suturing the descending branch of the lateral circumflex femoral vascular and posterior tibial vascular to reconstruct the blood supply of transplanted flaps, repairing lateral femoral cutaneous nerve to recover their sensation, fixing tensor fasciae in the calcaneum to add their stabilization. RESULTS: All flaps survived completely,the wounds healed in the initial treatment, follow up 3 to 48 months, twenty-six cases achieved partial sensation, good contour and stabilization. CONCLUSIONS: The anterolateral thigh flap is an ideal flap for repairing widespread defects of traumatic soft tissue in heel, because it has such advantages as adequate blood supply, big dermatosis area and covert donor site, furthermore, nervi cutaneous femoris lateralis and tensor fasciae offer the good sensation and adequate stabilization. PMID- 17286003 TI - [Clinic application of compound flap pedicled with arterial arch of palpebral margin]. AB - OBJECTIVE: To study the clinic application of compound flap pedicled with arterial arch of palpebral margin in repairing severe full defect of eyelid. METHODS: According to eyelid structure and the defect size, the two compound flaps were designed beside the defect based on the arterial arch of the palpebral margin. If the defective area was too large, the lateral compound flap may be extended to lower or upper eyelid 0.5 cm away from the outer canthus, then cut and propelled the two compound flaps to repair the full eyelid defect. RESULTS: 20 cases had been cured with this method since 1998. In this cases, 4 cases were basal cell carcinoma of eyelid, 2 cases were squamous carcinoma, 3 angiomas, 6 chromatophore nexuses, 3 traumatic defects, 2 congenital defects. The largest length of eyelid full defect was 1.7 cm and the smallest was 0.8 cm. 6 cases were upper eyelid defect and 14 cases were lower eyelid defect. All the compound flaps survived completely without any complications. All cases obtained satisfactory results functionally and esthetically. CONCLUSIONS: Repairing full eyelid defect with the compound eyelid flap is the same kind tissue repairing. It can not only provide enough tissues to primary repair large full defect of the upper or lower eyelid to restore normal anatomical structure and appearance of the eyelid, but also is easy to be operated without severe secondary deformities. The arterial arch of the palpebral margin is constant and the blood supply of the compound flap is reliable. It is an ideal method of repairing the eyelid defect. PMID- 17286004 TI - [Activity changes of protein kinase C in effect of interferon-gamma on wound healing and cicatrisation]. AB - OBJECTIVE: To study the roles of protein kinase C (PKC) in effect of interferon gamma (IFN-gamma) on wound healing and cicatrization. METHODS: IFN-gamma was applied on the wound and into the scar tissues of rabbit ear before or after wound healing. PKC activities in the tissues from 0, 3, 6 d, 11-16 d post wounding and from 14, 30 and 45d post-epithelization were measured by phosphorus (32p) incorporation. The time of wound epithelization and scar changes were also observed. RESULTS: The PKC activity in granulation tissue, wound margin tissue and scar tissue elevated obviously in comparing with that of normal skin (P < 0.01). IFN-gamma did not change PKC activity (P > 0.05). But it delayed the wound healing (P < 0.01) and inhibited scar hyperplasia (P <0.05). CONCLUSIONS: PKC might not mediate the signal of IFN-gamma inhibiting the wound healing and scar hyperplasia. But PKC might be related to the wound healing and scar hyperplasia. PMID- 17286005 TI - [Establishment of immortal lymphoblastoid cell bank of keloids pedigree]. AB - OBJECTIVE: To provide perpetual research materials for long term studies by establishing immortal lymphoblastoid cell bank of keloids pedigree. METHODS: The immortal lymphoblastoid cell lines of keloids pedigree were established by Epstein-Barr virus transformation of peripheral blood B lymphocytes. RESULTS: 27 immortal lymphoblastoid cell lines of keloids pedigree were obtained successfully, all of the immortal lymphoblastoid cell lines were successfully revivificated after been frozen in liquid nitrogen. CONCLUSIONS: It is important to establish immortal lymphoblastoid cell bank of keloids pedigree and provide long-term DNA materials for deep study of keloids in the future. PMID- 17286006 TI - [The effects of tetrandrine on activity of collagenase derived from human hypertrophic scar]. AB - OBJECTIVE: To observe the effect of tetrandrine on activity of collagenase derived from human hypertrophic scar for the sake of clarifying the mechanism as tetrandrine acting on scar. METHODS: The experimental concentration was controlled below that of cell proliferation inhibited, SDS-PAGE electrophoresis was adopted to separate collagenase from extracellular matrix, and then activated by trypsin analyzed the activity of collagenase with density scanning apparatus. At the same time quantity of extracellular collagen was measured using improved chloraseptine T oxidizing assay, moreover analyzed correlation between activity of collagenase and quantity of extracellular collagen. RESULTS: In the concentration below the lever of inhibiting fibroblast proliferation, the total activity of collagenase could be significantly increased by tetrandrine with dosage-dependence associated with quantity of extracellular collagen reduced, which was much greater than that of triamcinolone. CONCLUSION: Increasing activity of collagenase on degradation of collagen even in a lower concentration was one of the mechanisms of tetrandrine treating hypertrophic scar. PMID- 17286007 TI - [The modified sternal elevation for pectus excavatum]. AB - OBJECTIVE: To improve sternal elevation for pectus excavatum to be more simple, less injured and less recurrent. METHODS: We modified procedures for the sternal elevation for pectus excavatum by dispersal of the shortened fibrous bundle connection with central tendon of the diaphragm, correction of the reverse angle of sternocostales joins, transverse cuneiform anterior osteotomy of sternum and reconnection of oblique resected costal cartilage. RESULTS: Since March 1997, 8 children (4 - 10-year-old) with the pectus excavatum have been treated by this modified sternal elevation, 4 of them who suffer from quick heart pulse improved their heart rate immediately during the operation, all patients have less bleeding and good cosmetic appearance without any complications. There were satisfactory results without recurrence after 6 months to 1 year follow-up. CONCLUSION: The modified sternal elevation for pectus excavatum is safe, effective and reliable method. PMID- 17286008 TI - [Cryotherapy combine with pingyangmycin for the treatment of venous malformations]. AB - OBJECTIVE: To observe the therapeutic effect of 120 cases venous malformations treated by cryotherapy combine with pingyangmycin. METHODS: Pingyangmycin was injected into venous malformations and cryotherapy with liquid nitrogen was followed immediately. RESULTS: Cure rate was 77.5%, incomplete cure rate was 17.5% and efficiency rate was 5%. CONCLUSIONS: The method of cryotherapy combine with pingyangmycin injection to treat venous malformations has good effect. PMID- 17286009 TI - [Clinical research of improved plastic and reconstruction of anus in situ]. AB - OBJECTIVE: To explore the effect of the improved plastic and reconstruction of the anus in situ. METHODS: Improved plastic and reconstruction of anus in situ was performed in 38 cases of low rectal cancers operated while Miles radical operation. Improvement includes: (1) The internal sphincter was rebuilt with 4 layers of muscle layer of the endmost of colon. (2) The last of gracilis was divided into 2 parts to reconstruct the superficial part and deep part of external sphincter muscle. (3) The rectum cape improvement is to firmly stitch the levator ani outside the external sphincter muscle in front of the colon. (4) The rectum valve is improved into three artificial rectum valves. RESULTS: The form and function and their long term survival rate were good, the rate of superior anus function was 94.73%. CONCLUSION: It mains the results of improved plastic and reconstruction of anus in situ is near that of normal persons. PMID- 17286010 TI - [Visualization of the adult penis and adjacent structure of the Chinese visible human]. AB - OBJECTIVE: To build digitized visible model of the adult penis and adjacent structure of the Chinese visible human, providing morphological data for plastic plerosis of external genitals diagnosis and the adult penis surgery planning. METHODS: Cross-sectional images of fresh tissues from the Chinese visible human dataset and the visible penis and adjacent structure dataset were reviewed, the structures of the penis and adjacent structure were confirmed on a section-by section basis. Three-dimensional computer reconstructions of the penis and adjacent structure were generated from these data by surface rendering. RESULTS: The quality of the computerized 3D-reconstructed images was distinct and perfect. The adult penis and adjacent structure were all reconstructed and displayed jointly. All reconstructed structures can be represented individually or jointly. Any diameter and angle of the structures reconstructed could be measured conveniently. CONCLUSIONS: The digitized model of the penis and adjacent structure offer unique insights into the complex penis anatomy, providing morphological data for plastic plerosis of external genitals diagnosis and surgery planning. PMID- 17286011 TI - [The effect of pcDNA3.1-vEGF165 recombined vector on wound healing and the expression of collagen type I, III mRNA in wounded tissue]. AB - OBJECTIVE: To examine the effect of pcDNA3.1-VEGF165 vector to the angiogoiesis, expression of collagen type I and type III mRNA in soft tissue injury model. METHODS: Thirty two Sprague-Daulay rats,weighted (180 +/- 20) g, were made tissue injury in the bilateral of vertebral region. Round wound (diameter 12 mm) was made by perforex on the back, removed the skin and 2 mm muscle, one side was experimental group by random and the other as control. The wound was done with sodium chloride (0.2 ml) in the control group, with the recombinant VEGF165 vector (0.2 ml, 200 mg) in the experimental group. The wound healing and other general state of health was observed after the operation. The specimens were obtained at 3,5, 7,14 and 30 days after injury. Draw the materials from the rats at the same time, all samples were divided into two parts. one ( > 0.1 g) was conserved in refrigerator at - 80 degrees C, which was extracted total RNA by TRIZOL, design the primer of rat's collagen type I and type III, RT-PCR analysis indicated that collagen type I, III. The other was fixed by 10% formalin. Examine wound healing of local tissue and count it' s MVD by HE staining. RESULTS: All the rabbits were well alive, no death or infection. Wound healing time was shorter than the control one (14.2, 17.4 d). Inflammatory cell infiltrate, cellula intersitialis, fibroblast, collagen and the density of angiogenesis were more in the experimental group than in the control one. The MVD was significant difference between the two groups at 1, 2 weeks are 63.38 +/- 9.20, 52.72 +/- 7.06 and 76.64 +/- 12.27, 66.84 +/- 9.82 (P < 0.05). The expression of collagen type I , III mRNA was found in the third day, the peak was in the second week and then degression. The collagen type I , III mRNA and beta-actin specificitic belt were found and its initial template volume different, the results was trend of RT PCR obtained. CONCLUSIONS: The local application of pcDNA3.1-VEGF165 can enhance the expression of collagen type I, III mRNA, enhance angiogenesis and extra cellular matrix, both of which can shorten healing time of tissue injury. PMID- 17286013 TI - [Intellectual property rights and right of access to medicines]. AB - The agreement on trade-related aspects of intellectual property rights (trips) was established in 1994 simultaneously with the founding of the world trade organization (wto). the TRIPS agreement requires all WTO member states to grant patent protection for pharmaceutical products or processes for a period of at least 20 years. However only a few of the hundreds of pharmaceutical products patented every year involve new molecules. It is increasingly urgent to enhance the transparency and efficiency of the patenting process for pharmaceutical products. It is especially important for developing countries to increase scrutiny of how patents are processed and granted. This is necessary to prevent the detrimental effects of patenting of non-innovative products on access to medicines. PMID- 17286012 TI - [Effect of vacuum assisted closure on collagenase activity in human chronic wound]. AB - OBJECTIVE: To study the variations of collagenase activity in exudates of human chronic wound before and after treatment of VAC so as to partly disclose the mechanisms of VAC in promoting chronic wound healing. METHODS: The exudates of acute wounds (postoperative breast cancer) were postoperatively collected at day 1, 2, 3, and in 6 chronic wounds (4 cases of venous ulcer, 2 cases of pressure sore) the exudates were also collected before and 2, 4, 6 days after the treatment with VAC. The type-III collagen degradation from the exudates was checked with zymography timepoint. The types of the collagenase in exudates were evaluated by using doxycycline inhibition. RESULTS: Drainage fluids from acute wound might degrade type-III collagen partly with no changes at day 1, 2, 3. There were high collagenase activities in chronic wound exudates. Exudates from patients before treatment with VAC can degrade type-III collagen completely. But collagenase activities became less and less after VAC. Doxycycline inhibition tests indicated that it can't inhibit the activity of collagenase at 100 micromol/L concentration, until it reached 600 micromol/L. CONCLUSIONS: Collagenase activity is elevated in chronic wounds. VAC may be lower the collagenase activity, prevent collagen from degrading abundantly and promote wound healing. Collagenase is mainly MMP-1 type (fibroblast-type) in chronic wound exudates. PMID- 17286014 TI - [Counterfeit medicines: a growing threat]. AB - The medical drug market has undergone considerable transformation in recent years. Like other products, medicines have been affected by globalization. Free trade policies have had a number of negative effects including a reduction in quality control not only for some products but also for raw materials and finished products. The global environment has also created conditions conducive to counterfeit medicines. The term counterfeit medicine is defined differently from one country to another in terms of quality, legality and fraudulent intent. This situation prompted the WHO to propose the following definition: "A counterfeit medicine is one which is deliberately and fraudulently mislabeled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products and counterfeit products may include products with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging." Weak pharmaceutical regulation often compounded by widespread corruption in developing countries has greatly facilitated the development of this illicit market with harmful and costly effects on public health. Due to the lack of pharmocovigilance accidents involving use of counterfeit drugs go unreported. For this reason it is not possible to measure the economic impact. While counterfeiting has become a major threat in developing countries, it also affects industrialized countries. Fraudulent behavior occurs all over the world. PMID- 17286015 TI - [Quality of medicines in least developed countries]. AB - Due to worsening economic conditions and poor enforcement of existing pharmaceutical and customs regulations, third world countries are faced with a growing threat from counterfeit and substandard medicines. With the expansion of illicit markets in urban areas, the sales of medicines of uncertain quality and origin are increasing. Most victims of this illicit trade are among the world's poorest populations that cannot afford to buy quality drugs through private sector distribution channels. National pharmaceutical programs promoting universal access to essential generic medicines at reasonable cost are the key to curbing this problem. A system based on strict, rational pharmaceutical purchasing and distribution policies with quality assurance at every level of the supply chain is needed to guarantee that patients receive safe effective high quality healthcare products. PMID- 17286016 TI - [Role of an association in promoting pharmaceutical quality assurance: transfer of know-how based on the buddy system]. AB - The pharmaceutical world is undergoing rapid and radical changes with increasing complexity. Countries with limited resources are particularly powerless faced to these changes that have had a particularly strong impact on their pharmaceutical systems. To achieve the level of performance required to ensure continuous supplies of quality pharmaceutical products, pharmaceutical systems must be organized on the basis of quality assurance principles that use change as a motor of development. Implementation of quality assurance schemes provides management tools for gathering and processing the information necessary to develop an infrastructure satisfying the demand for quality medicines. Organization of such systems must be based on process improvement. In this framework, associations specialized in such pharmaceutical quality assurance can play a special role. The Medico-Pharmaceutical Humanitarian Group (French acronym, CHMP) is a humanitarian association that provides personnel for development and action in health-related products. The mission of the CHMP is to assist procurement and distribution structures in developing countries to achieve sustainable development by transfer of technical know-how. PMID- 17286017 TI - [Status of research and development for control of tropical diseases: hypocrisy, indifference or lack of coordination]. AB - Tropical diseases neglected by the pharmaceutical industry usually involve developing countries. Neglected diseases can now be divided into two groups. The first includes the big three infections i.e., malaria, HIV/AIDS, and tuberculosis, that present strategic and political overtones. The second group includes a host of other fatal infections including worms, trypanosomiasis, and leishmaniasis. Fundamental research on neglected diseases has been highly productive, but there has been little success in transferring research findings to a pharmaceutical industry unwilling to take the risks associated with developing new drugs on its own. However several public-private initiatives have revived hopes of developing new products with growing involvement of industries in developing countries (India and Brazil) despite the high risks associated with fluctuating demand for medicines or funding shortages. To meet the need for testing new drugs, more clinical facilities and better patient recruitment will be needed in endemic countries. Although these new efforts to control neglected diseases are encouraging, there is now a need for coordination. Clinical research in developing countries must be organized in compliance with international principles of ethics. Testing must be aimed at validating fundamental data from industrialized countries. Appropriate incentives must be given to ensure that pharmaceutical companies use research findings for new product development. In this context, the time seems ripe for the establishment of an independent laboratory for technological innovation in neglected diseases. Such a facility could not only validate scientific data but also supervise the development of clinical applications from research data. PMID- 17286019 TI - [E-med: illustration and vector of globalization in healthcare]. AB - Destined for healthcare professionals interested in public health policy in developing countries, E-med is one of the few francophone forums on essential medicines. Bringing together users with diverse backgrounds, discussion groups illustrate the effects of globalization on health policy: disappearance of distance, convergence of political and sanitary issues, enhanced cooperation between public and private sectors, coalitions of heterogeneous players and destruction of national and international barriers. Having benefited from the development of the Internet in recent years, as a secondary tool, E-med, must now evolve with this tool that is now ubiquitous in international health policy. PMID- 17286018 TI - [WHO program for prequalification of antiretroviral, antimalarial and antituberculosis drugs]. AB - Partnered with UNICEF, UNAIDS and the UN Population Fund, and receiving support from the World Bank, the WHO Prequalification Programme provides a solid, scientific assessment of the quality of both generic and patented medicines, based on internationally harmonized standards for evaluating information on product quality and bioequivalence, inspecting manufacturing sites, and undertaking quality control of pharmaceutical production. Agencies and organizations who procure medicines can be assured that products prequalified by WHO are of proven quality and that they do not themselves have to test these products. The WHO list of prequalified products also means that agencies procuring medicines can choose between several manufacturers offering the same quality product, which offers scope for negotiating lower prices. As a result of this Programme, capacity to manufacture generic products of assured quality is increasing, as is capacity to monitor that quality. Initially focusing on medicines for HIV/AIDS, TB and malaria, the Programme is now being expanded to also cover medicines for reproductive health. PMID- 17286020 TI - [Control of malaria: market for artemisinin and its derivatives]. AB - Artemisinin compounds derived from the Artemisia annua plant provide the raw material for new artemisinin based combined therapies (ACT) against malaria. The purpose of this report is to present the different steps in production of these compounds from planting to harvesting, extraction, purification, chemical transformation and final formulation. Factors affecting cost are given special focus to gain better insight into ways of holding down the purchasing price. We also describe the consequences that the April 2004 decision by several international organizations (e.g. WHO and Global Fund to fight AIDS, tuberculosis and malaria) to make ACT the reference treatment for malaria has had on the supply of ACT, i.e., shortages with a sharp price increase followed by overinvestment and surpluses with a sharp price decrease. In view of these fluctuations, we discuss whether regulation is necessary and who should intervene. PMID- 17286021 TI - [Access to essential medicines in Africa: a global approach]. AB - Establishment of programs to assist procurement of antiretrovirals (ARV), antimalarials (ACT) and antituberculosis drugs led to careful evaluation of the performance of national central medical stores purchasing essential medicines. Substandard central medical stores were excluded from support programs and procurement was carried out under the responsibility of UN agencies. This situation underscores the need to develop local competencies and to consolidate national procurement infrastructures. The Association of Central Medical Stores for Essential Drugs (French acronym, ACAME) with the support of the French Cooperation Agency is working to improve the performance of national central medical stores. The main components of ACAME's program are multidisciplinary training for members, exchange of experience and consolidation of work tasks, notably for its progressive purchase policy, that must be based on consensus selection of suppliers. The creation of FIAM/UNITAID offers a glimmer of hope for sustained financing and for ensuring delicate supplies (second line and pediatric ARV, ACT) with which Central Medical Stores wish to be associated. Focus on supply tends to overshadow other issues affecting rational use of medications. Indeed deviations can be found in effective application of cost recovery and in the pricing mechanism for peripheral medications. Prescription of generic drugs and their availability in hospitals is still a problem notably for outpatients and patients with chronic illnesses. Outlying storage facilities need to be upgraded to ensure that pharmaceutical products acquired according strict quality assurance requirements remain stable. The presence of a thriving and dangerous illicit market will require stronger action from national authorities and better coordination between sectors. PMID- 17286022 TI - [Study on the availability and cost of medicines in the private sector in Mali]. AB - As part of a drive to implement a national pharmaceutical policy in Mali, a joint commission was set up to monitor pharmaceutical products intended for human usage. The commission recommended a study to evaluate the costs of drug procurement by private wholesale importers in Mali, prices charged by wholesalers to private pharmacies and prices paid by patients in private pharmacies. This report describes a study that was carried out in the district of Bamako and regions of Sikasso, Segou and Kayes in June 2004. Data was compiled on 13 importers and 89 pharmacies. Findings showed that the prices of products were relatively stable and that the prices of generic products were highly variable. These findings led to two decrees regulating the price of generic drugs, i.e., first in the public sector (2003) and then in the private sector (2006). PMID- 17286023 TI - [Create or strengthen the drug committee at a hospital]. AB - The goal of the hospital pharmaceutical committee is to improve the availability, accessibility and use of medicines and medical devices. These activities can have substantial impact on the quality of care. This report describes the missions, operational mode and operational conditions of the pharmaceutical committee. The purpose is to encourage hospital pharmacists in countries with limited resources to develop rational practices for the management and use of pharmaceutical products in their training programs in collaboration of healthcare providers. PMID- 17286024 TI - [Survey on the illicit drug market in Cotonou, Benin in March 2003]. AB - Illicit sale of medicines is a serious public health problem in Africa. In Benin, an informational program was undertaken to fight this threat. A three-day survey on consumption of medicines was conducted in various areas in Cotonou. The purpose was to evaluate purchasing practices so that related concerns and beliefs could be used to craft messages for the next campaign to curb illicit medicines. In addition to being a tool for message development, this survey will be used as an evaluation tool to measure message impact during and after the information campaign. A questionnaire designed to evaluate several aspects of drug purchasing behavior was administered by investigators in 600 randomly selected households. The main findings were as follows. Repressive measures to reduce the sale of counterfeit medicines on the illicit market are necessary but inadequate. New campaign messages for targeted groups are necessary since 86% of people interviewed thought that medicines acquired from street vendors were of good quality. More importantly it will be necessary to make legitimate medicines more accessible and affordable (generic drugs) and to simplify dispensation procedures allowing prescriptions to be filled followed by appropriate professional counsel. PMID- 17286025 TI - [Prescribe and advise freely]. AB - Physicians know how totally unrealistic it is to expect drug companies to furnish reliable comparative information to assist therapeutic decision-making. All hope in this regard must be founded on personal effort to sort through available data and on independent reasoning. This evaluation process must be based on international nonproprietary names (INN) far removed from the advertising campaigns devised by companies. PMID- 17286026 TI - [Study on the quality of pharmaceutical advertising in a pharmacy in Congo Brazzaville]. AB - This two-year study was conducted to evaluate the quality of advertising material supplied by pharmaceutical sales representatives to a pharmacy in Pointe Noire. Findings showed that company material were not helpful in informing healthcare providers properly. PMID- 17286027 TI - [UNITAID: an innovative and collective financing system for the fight against malaria, AIDS and tuberculosis]. AB - Malaria, AIDS and tuberculosis cause more than 6 million deaths a year in developing countries. And yet medicines allowing effective treatment either exist already or could be designed in forms adapted to the populations most severely affected by these pandemics (e.g., pediatric antiretroviral formulations suitable for developing countries). By providing sustainable predictable revenues, UNITAID promises to be a powerful tool to respond to the specific needs of developing countries in terms not only of leveraging price reductions but also of developing appropriate drug forms and diagnostic techniques not currently on the market. Stable financing as well as negotiation of large-volume procurement programs for several countries will make it easier for manufacturers to predict requirements and avoid shortages. UNITAID is an independent structure that complements the existing organizations involved in the fight against these pandemics. It intervenes only at the request of beneficiary countries using local human resources and logistics and works to improve the infrastructure facilities whenever necessary. PMID- 17286028 TI - [Cost recovery and reinforcement of the primary healthcare system in a rural community in Casamance, Senegal]. AB - This study was conducted by two pharmacists from Caen, France and two healthcare officials from the region of Ziguinchor and Bignona in Casamance, Senegal. Data showed that with good community awareness and proper supervision a minimum cost recovery policy could be implemented at health posts (cases de sante). This approach enables purchasing of more medicines and lowers operating costs. Additional funding is necessary to pay for building renovation and meaningful wages for healthcare workers. PMID- 17286029 TI - [Poor access to antiretroviral treatment in French-speaking Africa: situation in 2004]. AB - A survey by questionnaire and interview was carried out with persons in charge of purchasing central structures and AIDS control programs in 18 French-speaking African countries between June and October 2004. Survey data showed that a total of 3300 patients received antiretroviral (ARV) treatment during the study period. This corresponds to a treatment rate of 0.1 to 9.6% of the number of patients requiring ARV treatment. All countries reported interruptions of the ARV supply for a variety of reasons. The main causes were budgetary issues and procedural complexity involving financial aid. The prices charged to the patients varied greatly in function of national policies. Cost price also varied in function of the negotiating leverage of the purchasing central. Improve general access to ARV treatment and reducing the number of supply shortages will require more training in management and distribution of medicines. It would also be useful to improve communications between the persons in charge of national purchasing structures. PMID- 17286030 TI - [Action of Pharmaciens Sans Frontieres International Committee: an example from Cambodia]. AB - Pharmaciens Sans Frontieres Comite International (PSFCI) has been active in Cambodia since 1990. Cambodia is one of the poorest countries in the world and has the highest rate of HIV infection in Asia. Early on the PSFCI was faced with problems related to sexually transmitted diseases (STD) and AIDS. Based on this field experience PSFCI has been able to better understand the pandemic and to define control strategies. Since 1996 PSFCI has been contributing to the implementation and development of multi-component strategy against AIDS and other STD. One component of this strategy involves upstream intervention with prevention and awareness campaigns and deployment of methods best suited to the cultural and socio-economic environment of vulnerable populations. Another component consists in implementation of a screening and treatment network of competent healthcare professionals able of providing patients not only personalized confidential care but also the psychological support necessary to ensure long-term compliance with treatment. The last component involves training of healthcare personnel and social workers so that these programs can be extended throughout the country. PMID- 17286031 TI - [Drug supply for HIV patients in day care centre in Republic of Congo: the French Red Cross experience]. AB - The commitment of the French Red Cross Society to fight against HIV-AIDS in Africa is based on day care centres (DCC) set up and operated within public hospitals, for instance in Brazzaville and Pointe-Noire in Republic of Congo. These outpatient facilities offer global care including supply of medicines and antiretroviral therapies. The regular supply of medicines, laboratory and medicals materials necessary for the follow-up of the patient is the key of the quality of these structures and their durability. The French Red Cross guarantees this supply chain in countries where no secure pharmaceutical purchasing centre exists, as for exemple in Republic of Congo. PMID- 17286032 TI - [Extraction of artemisinin and synthesis of its derivates artesunate and artemether]. AB - Artemisinin is extracted from Artemisia annua, a shrub also known as sweet wormwood that was used in traditional medicine in Asia for more than 1500 years. Recent studies in numerous malarious zones have demonstrated the effectiveness of artemisinin and have reported no evidence of the resistance now associated with almost all other antimalarials on the market. Despite its remarkable activity, artermisinin is not accessible to many patients due to high cost. This situation confronts all players in the fight against malaria with the urgent need to develop a simple process to produce massive supplies of artemisinin and its derivative at an affordable price. The purpose of the study described here was to develop a simple, cost-effective method that could be used by all professionals to extract artemisinin and transform it into artesunate or artemether. Artemisinin was extracted with dichloromethane and purified on the basis of variations in polarity and in the hydrophile/lipophile balance of solvents. Transformation into artesunate was a two-step process involving reduction to dihydroartemisinin using diisobutylaluminium hydride (DIBAL) followed by esterification using succinic anhydride. Artemether was obtained from dihydroartemisinin using boron trifluoride. Extraction using dichloromethane presents several advantages. Since dichloromethane is not explosive it can be safely transported and used for extraction on farms where Artemisia annua is grown. Evaporation and recovery of dichloromethane is relatively easy so that it can be re-used. These advantages result in a significant decrease in purchasing and shipping costs. Extraction on the farm eliminates the expense and facilities that would otherwise be required to transport and store leaves at the laboratory (250 kg of leaves yield 4 to 5 kg of raw artemisinin extract that yields approximately 1 kg of pure artemisinin). The low-cost process described here is feasible for any pharmaceutical laboratory including those in developing countries. PMID- 17286033 TI - [Role of traditional medicines in Africa]. AB - Plants used for traditional medicines in Africa have been the focus of many chemical, pharmacological and toxicological studies. Based on a better understanding of these traditional plants, small private laboratories and pharmacists have been able to produce enhanced traditional medicines (ETM). These ETM have contributed to health of populations and reduced reliance on imported medicines. PMID- 17286034 TI - [Assessment of compliance with ARV treatment in Africa]. AB - This study was conducted in health facilities in the capitals of five sub-Saharan African countries (Cotonou, Benin; Bangui, Central African Republic; Libreville, Gabon; Yaounde, Cameroon; and Casablanca, Morocco). The purpose was to investigate factors promoting and impeding compliance with antiretroviral therapy (ART) and cotrimoxazole (CTX) prophylaxis in adult patients. Patients were interviewed immediately after follow-up examination to identify the problems that they encountered and the solutions that they proposed to improve compliance. Compliance was assessed based on three measurement modalities, i.e. skipping medication during the four days prior to attendance, counting the number of remaining tablets, and attendance assiduity. Compliance scores varied according to measurement modality from 65% to 90%. All patients underlined the impact of treatment on their daily life and the difficulty of following the prescribed regimen properly. Impeding factors for compliance were treatment-related hunger, lack of information, out-of-pocket expenses (including laboratory tests, transportation, and loss of income), side effects, long waiting time at the treatment centers, and fear stigma and discrimination. Efforts to increase access to treatment can only be successful if accompanied by measures to promote compliance. PMID- 17286035 TI - [Evaluation of public awareness campaigns on counterfeit medicines in Cotonou, Benin]. AB - A public awareness campaign mainly TV and radio announcements to promote public awareness of the dangers of counterfeit medicines was developed based on survey data collected in 2003. The survey was designed to evaluate the purchasing practices of consumers in Cotonou, Benin with regard to medicines. Based on findings, several recommendations were made for crafting new messages about generic drugs and the dangers of the illicit medicines market. Evaluation of the results of the new campaign that lasted 9 months showed that: most respondents stated that the campaign announcements were effective in increasing their awareness; nine out of 10 persons understood the messages on the dangers of the illicit market; a net decrease in buying on the illicit market was observed among respondents that increased their awareness; the frequency of house calls by illicit vendors decreased. Most respondents stated that they requested generic drugs spontaneously. The preferred sources for procurement of generic medicines were public health facilities and pharmacies. PMID- 17286036 TI - [Rational use of medicines]. AB - Every body speaks about inappropriate use of medicines and each one gives his own explanation. Politicians are telling about the waste of medicines and the money of their national budget. Citizens are saying that the physicians prescribe more than necessary for treatment and blame them as one part of the financial burden weighting on their family budget. Physicians give different explanation and think that the rational use of medicines is a sort of pressure to limit their freedom to prescribe what it seems to them necessary and better for their patients. Pharmacists dispensing medicines consider the prescription as a physician's prerogative and prefer to stay neutral in this debate. Within this large range of opinions, it is difficult to find general consensus, so that every body take care to not declare his proper opinion about the subject, the causes and the adequate solutions. Finally no changes take place in this issue. However, neither the government as responsible for the citizen's health, nor the health professionals and international organisations, are facing their complete obligations toward the populations by ensuring to them that the medicines are administered according to the health need of the patients, efficacious and safe , in doses that meet their own individual requirements, for an adequate period of time, and at the lower cost, and be secured against misuse by the pharmacist before the delivery to the patients. This is a worthwhile programme, but unfortunately without designate takers or promoters until now. PMID- 17286037 TI - [Preselection procedure for medical devices suppliers at the essential medicines and generic drugs purchasing central in Togo (CAMEG-Togo)]. AB - One of the main objectives of pharmaceutical policies in developing countries is to ensure accessibility and affordability of good quality medicines for the population. The Essential Medicines and Generic Drugs Purchasing Central (French acronym, CAMEG-Togo) is a not-for-profit association established in 1998 to ensure procurement for public and not-for-profit private public health facilities within the framework of recovery of costs. Although attention has been focused mainly on medicines, medical devices account for a growing part of the pharmaceutical products purchased by central stores, hospitals and health programs. Recognizing this need in 2002, CAMEG-Togo in collaboration with the French cooperation agency decided to upgrade its competency in evaluating the quality of medical devices. For that purpose the information sheet used to preselect suppliers for international tenders and the technical specifications sheet for medical devices was revised and pharmacists responsible for processing these files were given specific training. European directive N 93/42/CEE of 14 June 1993 is currently used by CAMEG-Togo as the regulatory basis for preselection of medical device suppliers. Referencing based on American regulatory requirements is now under way to widen the scope of suppliers eligible for preselection. The purpose of this article is first to describe the main guidelines of the European directive used by medical device manufacturers to obtain EC certification and second to present the procedures used by the CAMEG Togo to preselect medical device suppliers, with special focus on the technical specifications sheet. PMID- 17286038 TI - [The problem of oxygen in developing countries]. AB - Availability of a reliable oxygen (O2) supply is critical for hospitals in developing countries. The AIDS pandemic that is associated with severe pulmonary infections has further enhanced this problem. Today in 2006, even though a number of financially viable solutions adapted to conditions in developing countries are available, lack of oxygen is still a cause of death in Africa including in some capital cities. Hospitals in industrial countries have wall outlets supplied from liquid O2 storage tanks (-183 degrees C). However this solution requires advanced cryogenic technology with storage as well as transportation of liquid O2. In developing countries, O2 is supplied from pressurized O2 cylinders (200 bars) sometimes stored in racks to supply wall outlets but more often moved from bed to bed as needed. This solution is expensive because of the cost of transportation on poor roads in all areas outside capital cities. Frequent supply shortages lead to major disruptions in care quality. Properly maintained O2 concentrators can provide a highly effective low-cost easy-to-use solution for health facilities in developing countries. The pressure swing adsorption (PSA) process based on reversible nitrogen adsorption is a reliable economical autonomous oxygen production process ideally suited to hospitals in developing countries. It can be used to supply wall outlets or fill cylinders. Return on investment is achieved within one to two years. PMID- 17286040 TI - The concept of life and its significance in the construction of the new ecosystem ecology of Bernard Patten, Sven Jorgensen and Milan Straskraba. AB - In a series of articles, three system ecologists, B. Patten, S. Jorgensen and M. Straskraba attempt to construct a new ecosystem ecology. In this effort, an innovative ecological definition of life that originates from the cognitive domain is prevalent. To be more specific, living entities are defined as those who make models of reality. Through the exploration of this definition, we will try to point out the ontological and the epistemological characteristics of the new ecology. These characteristics facilitate the integration of physicochemical, biological and human systems into a common framework. Indeed, system ecologists attempt to unify the inorganic and the organic world, including human beings, under a universal evolutionary scheme. This scheme is organized around an innovative scientific hypothesi, namely the exergy storage hypothesis. PMID- 17286039 TI - Keeping up with Dobzhansky: G. Ledyard Stebbins, Jr., plant evolution, and the evolutionary synthesis. AB - This paper explores the complex relationship between the plant evolutionist G. Ledyard Stebbins and the animal evolutionist Theodosius Dobzhansky. The manner in which the plant evolution was brought into line, synthesized, or rendered consistent with the understanding of animal evolution (and especially insect evolution) is explored, especially as it culminated with the publication of Stebbins's 1950 book Variation and Evolution in Plants. The paper explores the multi-directional traffic of influence between Stebbins and Dobzhansky, but also their social and professional networks that linked plant evolutionists like Stebbins with Edgar Anderson, Carl Epling, and the 'Carnegie team' of Jens Clausen, David Keck, and William Hiesey with collaborators on the animal side like I. Michael Lerner, Sewall Wright and L.C. Dunn and other 'architects' of the synthesis like Ernst Mayr, Julian Huxley and George Gaylord Simpson. The compatibility in training, work styles, methodologies, goals, field sites, levels of analysis, and even choice of organismic systems is explored between Stebbins and Dobzhansky. Finally, the extent to which coevolution between plants and insects is reflected in the relationship is explored, as is the power dynamic in the relationship between two of the most visible figures associated with the evolutionary synthesis. PMID- 17286041 TI - Zangerl and the Zeitgeist. PMID- 17286042 TI - Evolution vs. creationism. PMID- 17286043 TI - By the numbers. An annual resource guide filled with the numbers, rankings and financial figures that shape healthcare. PMID- 17286044 TI - cDNA cloning, characterization and expression analysis of DTX2, a human WWE and RING-finger gene, in human embryos. AB - The WWE domain is a conserved globular domain in several proteins and predicted to mediate specificprotein-protein interactions in ubiquitin and ADP ribose conjugation systems. The RING domain is a conserved and specialized zinc-finger motif with 40-60 residues binding to two zinc atoms, which is also probably involved in mediating protein-protein interactions. Here, from human fetal heart cDNA library, we identified DTX2, a human WWE & RING-finger gene, with high similarity with its homologues. Evaluation of full-length cDNA obtained by RACE indicated it encodes a protein composed of two WWE domains and a RING-finger region. The DTX2 gene located in human chromosome 7q11.23 spanning approximately 44.3 kb on the genome and the deduced protein is 622 amino acids. Northern analysis revealed DTX2 was expressed in the 18-week, 22.5-week human embryo hearts and adult hearts, especially with high levels in the 18-week and adult hearts. Taken together, these results indicate that DTX2 is a gene encoding a WWE RING-finger protein and involved in regulating heart development and heart functions. PMID- 17286045 TI - The complete mitogenome of Rhodeus uyekii (Cypriniformes, Cyprinidae). AB - The complete nucleotide sequence of the mitochondrial genome from the R. uyekii with a total size of 16,817 bp has been determined by long PCR technology. Mitogenome of R. uyekii encoding 13 putative proteins, two ribosomal RNAs and 22 tRNAs shows typical teleost mitogenome structure. Nucleotide composition, amino acid composition and codon usage are in the range of values estimated from other teleost mitogenomes. In the AT rich region of R. uyekii, several conserved blocks which are identified from vertebrates are observed in the genome. R. uyekii, the Korean endemic species, belongs to cyprinid fish from which the information of nine mitogenomes is available. To understand the phylogenetic relationships of Cypriniformes from the known mitogenome information, we analysed Cypriniformes mitogenome based on protein coding gene sequences. In spite of more resolved picture of phylogenetic interrelationships in cyprinid fish in this study, the further study with comprehensive taxon sampling for mitogenome information is strongly needed. PMID- 17286046 TI - Nucleotide sequence analysis of VP7 gene of Indian isolates of bluetongue virus vis-a-vis other serotypes from different parts of the world. AB - Bluetongue virus (BTV), a member of genus Orbivirus, a family Reoviridae, is a non-enveloped with double shelled structure and ten segmented double stranded (ds) RNA genome. The RNA segment S7 encodes an inner capsid serogroup specific viral protein VP7. To amplify coding region of VP7 gene of BTV, new primers, forward primer (18-38 bp) and reverse primer (1156-1136 bp), were designed using VP7 gene sequences available in GenBank. This primer pair successfully amplified cell culture adapted Indian isolates of BTV belonging to two different serotypes 1 and 18. The coding sequences of two Indian isolates of BTV (BTV-1H and BTV-18B) were cloned into pPCR Script-Amp SK (+) plasmid vector and transformed into XL10 Gold Kan ultracompetent E. coli cells. The positive clones selected by blue-white screening and colony touch PCR were sequenced. The sequence analysis revealed that there was 93-97% nucleotide sequence identity in VP7 gene of three different Indian serotypes of BTV. The VP7 gene sequences of Indian isolates have comparatively less sequence homology (< 80%) with American (US), and French isolates compared to South African (SA), Australian (AUS) and Chinese (PRC) isolates. In silico restriction enzyme profile analysis of VP7 gene sequences revealed that Indian isolates of BTV-1 can be differentiated from other BTV-1 isolates reported from SA, AUS and PRC using TaqI. Similarly the Indian isolates of BTV belonging to three different serotypes can be differentiated using EcoRI, Hae III and TaqI restriction enzymes. PMID- 17286047 TI - Molecular characterization of a bovine Y-specific DNA sequence conserved in taurine and zebu breeds. AB - The identification of new bovine male-specific DNA sequences is of great interest because the bovine Y chromosome remains poorly characterized in terms of physical and genetic maps. Since taurine and zebu Y chromosomes are structurally different, the identification of Y-specific sequences present in both sub-species is particularly important: these sequences are of evolutionary significance and can be broadly used for embryo sexing. In this work, we initially used the random amplified polymorphic DNA (RAPD) technique to search for male-specific sequences present as monomorphic markers in genomic DNA from zebu and taurine bulls. A male specific RAPD band was found to be present and highly conserved in both sub species, as demonstrated by Southern blotting, fluorescent in situ hybridization (FISH) and DNA sequencing. In a previous work, a pair of primers derived from this marker was successfully used in taurine and zebu embryo sexing. PMID- 17286049 TI - Cloning and expression of a 5-enolpyruvylshikimate-3-phosphate synthase gene from Halomonas variabilis. AB - A novel 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene of 1.35 kb was cloned from a cosmid library of Halomonas variabilis HTG7, inserted into vector pET-28a (+) and transformed in Escherichia coli BL21 (DE3). EPSPS was over expressed in soluble form after induction with IPTG at 30 degrees C and it showed a single band in SDS-PAGE, which corresponds to a molecular weight of 51 kD. Deduced amino acid sequence analysis showed that there is little homology with the aroA genes which encode glyphosate-tolerant EPSPS in known sources, such as E. coli K12 and Agrobacterium sp. CP4. The over-expressed EPSPS was purified on nickel-nitrilotriacetic acid resin and detected by Western blotting analysis. Enzyme activity measurements demonstrated that there were 4.27 units/mg in cell extract, compared with 0.049 units/mg of the control. There is an 87-fold increase in specific activity for EPSPS. PMID- 17286050 TI - Polyhedrin gene sequence and phylogenetic analysis of a nucleopolyhedrovirus isolated from Orgyia ericae Germar. AB - Molecular characterization of a nucleopolyhedrovirus (NPV) isolated from the diseased larva of Orgyia ericae Germar was firstly analyzed. The genomic size of O. ericae NPV was estimated to be 134.6 kb by restriction endonuclease analysis. The gene encoding the major structural protein, polyhedrin, was cloned and sequenced. Phylogenetic analyses using polyhedrin sequences revealed that O. ericae NPV (OeNPV) was a member of the Group II NPVs and was closely related to the BusuSNPV and OpSNPV cluster. Electron microscopic observations confirmed that OeNPV was a single nucleocapsid type virus (SNPV). PMID- 17286048 TI - Cloning and characterization of a novel trypsin inhibitor (BTIomega1) gene from Fagopyrum esculentum. AB - Based on the amino acid information of trypsin inhibitor of buckwheat (Fagopyrum Esculentum Moench), degenerated primers were designed and a full-length cDNA sequence named BTIomega1 (Buckwheat Trypsin Inhibitor) was amplified from the leaves RNA by using RT-PCR and rapid amplification of cDNA ends (RACE) methods. Sequence analysis shows that the 392 bp cDNA contained an open reading frame (ORF) of 216 bp, encoding 72 amino acids residues. The deduced amino acid sequence exhibits 96 and 93% homology with BWI-1 and BTI-2, a natural trypsin inhibitor from buckwheat seeds. Southern blotting suggested that three copies of BTIomega1 gene existed in the buckwheat genome. Moreover, a predicted secondary structure and 3D-structural model was constructed by homology modeling. To our knowledge, this is the first all-round report of the gene BTIomega1. The novel BTIomega1 gene has been submitted to the GeneBank under Accession No. DQ289792. PMID- 17286051 TI - Isolation and characterization of the RanGAP gene in the mosquito Aedes aegypti. AB - A duplicated 3'-truncated version of RanGAP was previously identified as Segregation distorter (Sd), the meiotic drive gene in Drosophila melanogaster. Here we report the cloning and characterization of the complete gene sequence for the RanGAP homolog from the mosquito Aedes aegypti. The 1995 bp cDNA sequence consists of a 113 bp 5' UTR and 130 bp 3' UTR, and encodes a 583 amino acid protein with high sequence identity with RanGAP homologues of several species. A 20,125 bp genomic DNA sequence contains the complete RanGAP gene, consisting of three exons and two introns. Intron 2 comprises 18,082 bp and contains multiple repetitive elements as well as putative coding regions. The RanGAP locus was mapped to the q-arm of chromosome 2. Because the meiotic drive gene (M(D)) in A. aegypti was previously shown to be tightly linked with the sex determining locus on chromosome 1, RanGAP is likely not the M(D) gene. PMID- 17286052 TI - Cloning and sequence analysis of ornithine decarboxylase gene fragments from the Ascomycota. AB - Ornithine decarboxylase (ODC; EC 4.1.1.17) catalyzes the initial step in the biosynthesis of polyamines, the conversion of ornithine to putrescine. Based on the most conserved regions of fungal ODCs, we designed and synthesized oligonucleotides to amplify homologous fragments of three important plant pathogenic Pyrenomycete fungi (Ascomycota), Magnaporthe grisea, Colletotrichum lindemuthianum and Fusarium solani, and one insect pathogenic fungus Metarhizium anisopliae. Cloning and sequencing of the amplified fragments revealed homologies of between 37 to 88% with other fungal ODCs. The predicted peptide sequences were compared by Clustal analysis and conserved sequences corresponding to the substrate and cofactor binding sites were identified. Comparative analyses of the ODC fragments isolated in this study, revealed high homology between them (68.3 81.1%) and also with other Pyrenomycetes such as Neurospora crassa (order Sordariales; 68.6-72.9%) and Fusarium graminearum (order Hypocreales; 70.8 88.1%). Data obtained in this work revealed that these fungi constitute a compact group separated from other eukaryotic ODCs. PMID- 17286053 TI - HFM1, the human homologue of yeast Mer3, encodes a putative DNA helicase expressed specifically in germ-line cells. AB - DNA helicases are known to play important roles in the maintenance of genome integrity including the replication of trinucleotide repeats in the cells. Here, we report the HFM1 gene, which encodes the putative human DNA helicase. The HFM1 gene comprises 39 exons mapping to human chromosome 1p22.2. The HFM1 cDNA encompasses 4931 nucleotides with a single open reading frame (ORF) of 1435 amino acid residues encoding a predicted 172 kDa protein (hHFM1). The deduced protein sequence shares similar domain and motif structures to those of Mer3, a DNA helicase of Saccharomyces cerevisiae; seven consecutive motifs conserved among the DEXH-box type of DNA/RNA helicases at the N-terminal and a single putative zinc finger motif at the C-terminal regions of the protein. Further, the HFM1 transcript is preferentially expressed in testis and ovary. Collectively, hHFM1 is the evolutionally conserved putative human DNA helicase, which may function as a modulator for genome integrity in germ-line tissues. PMID- 17286054 TI - 2007 resource guide. PMID- 17286055 TI - The new retirement reality: calculating the true cost of retirement income adequacy. AB - Recognizing that 401(k) plans are emerging as many employees' sole source of employer-sponsored retirement income, plan sponsors are increasingly adding paternalistic plan features to increase the amount--and effectiveness--of dollars invested in 401(k) accounts. The authors describe the results of a study they prepared for Hewitt Associates that assesses retirement income adequacy for individuals represented in a plan participant database of 1.8 million individuals. The study includes analysis of retirement income adequacy for the aggregate population as well as the results for different subgroups, reflecting factors such as whether individuals actively contribute; the impact of different levels of retiree medical coverage; and the presence of a defined benefit pension. Finally, the authors discuss how plan sponsors can bolster the adequacy of retirement income from 401(k) plans, depending on employer objectives. PMID- 17286056 TI - COBRA notice--bankruptcy--stay. Buchanan v. Golden Casting Corporation Hourly Health Benefit Plan. AB - In an absence of special circumstances, the automatic stay that protects an employer from suit while its bankruptcy is pending does not apply to an action brought against its employee welfare benefit plan under ERISA because the plan, not the employer, is the proper entity to sue for benefits. Similarly, the employer's automatic stay does not apply to the individual fiduciary sued for breach of fiduciary duty in administering the plan. The bankrupt employer has no property interest in either the plan assets or the assets of the individual fiduciary and, therefore, the stay does not protect them from suit. PMID- 17286057 TI - Health benefits--reimbursement--state law claim not preempted. Providence Health Plan v. McDowell. AB - A claim to enforce a reimbursement provision or a separate promise to reimburse a plan out of recovery from a responsible third party cannot be brought in federal court under ERISA, because it is a legal claim for monetary damages and ERISA allows fiduciaries to bring suit only for equitable relief However, a claim for reimbursement of medical benefits paid from a third-party settlement is a state law breach-of-contract claim that cannot be removed to federal court and is not preempted by ERISA. Thus, a plan can bring an action in state court for breach of contract against a participant or beneficiary who fails to reimburse the plan for medical benefits paid when he or she recovers from a third party in a settlement or through a judgment, as required by a reimbursement provision in the plan and/or a separate reimbursement agreement. PMID- 17286058 TI - Medicare Secondary Payer--liability of alleged tortfeasors. Mason v. American tobacco company. AB - The Medicare Secondary Payer (MSP) statute does not provide individuals whose medical costs have been paid for by Medicare with a right of recovery against alleged tortfeasors (wrongdoers). Tobacco companies are not self-insured primary plans under the MSP statute because they have no existing contractual obligation to pay the health care costs of those injured by smoking. PMID- 17286059 TI - 2006 ISSVD classification of vulvar dermatoses: pathologic subsets and their clinical correlates. AB - The International Society for the Study of Vulvovaginal Disease (ISSVD) has, as one of its major societal goals, the development and promulgation of nomenclature and classification of vulvar disease. A committee of the ISSVD has developed new nomenclature and classification for the specific area of vulvar dermatoses. This classification was approved by the ISSVD members at the most recent international congress, held in New Zealand in February 2006. PMID- 17286060 TI - In defense of Jeffcoate and Woodcock and their "vulvar dystrophy" terminology: the 2006 ISSVD presidential address. PMID- 17286061 TI - A qualitative study of women with vulvodynia: I. The journey into treatment. AB - OBJECTIVE: To evaluate women's experiences of accessing help and treatment for vulvodynia. STUDY DESIGN: Women who had participated in a vulvar pain management program were evaluated in a retrospective, qualitative, in-depth interview study. RESULTS: The women described their distressing symptoms of vulvodynia and their previous experiences of seeking help. The women thought that the delay to diagnosis contributed to the severity of their symptoms and that achieving a diagnosis was the first step on a path toward the acceptance of a chronic condition and a commitment to a management program. CONCLUSION: Vulvodynia is poorly recognized, and the delay to diagnosis adversely affects patients, exacerbating the severity of their symptoms. PMID- 17286062 TI - A qualitative study of women with vulvodynia: II. Response to a multidisciplinary approach to management. AB - OBJECTIVE: To evaluate the response of a group of women with vulvodynia who were participating in an integrated, multidisciplinary management program comprising medical evaluation and treatment, psychotherapy, physiotherapy and dietary advice. STUDY DESIGN: Retrospective, qualitative, in-depth interview study. RESULTS: Twenty-seven of 29 women reported a significant benefit, and 9 who had completed the program were pain free. All women appreciated the integrated approach, and even those who were not completely pain free found that they were able to manage their condition satisfactorily. CONCLUSION: Further evaluation of this program is warranted to assess whether it would be helpfulfor other women with this problem. PMID- 17286063 TI - Pilot study of sexual function and quality of life after excision for vulvar intraepithelial neoplasia. AB - OBJECTIVE: To compare sexualfunction and quality of life (QOL) in women with vulvar excision for vulvar intraepithelial neoplasia (VIN) with those in an age matched, healthy comparison group. STUDY DESIGN: This cross-sectional study contrasted women (n = 43) after vulvar excision for VIN with a healthy comparison group (n = 43). Participants were asked to complete the Female Sexual Function Index (FSFI) and the European Organization for Research and Treatment of Cancer QLQ-C30 to provide an assessment of sexual function and quality of life. Medical records of the participants were reviewed for pathology results, operative reports and medication history. Women with VIN were age matched +/- 2 years with healthy women attending a breast screening clinic. RESULTS: Most participants were Caucasian (76.6%) and smoked (69.8%). Women after excision had poorer scores in sexual function (p = 0.015) and QOL (p = 0.003) than healthy women. CONCLUSION: Impairment of sexual function after vulvar excision for VIN appears to be of the psychologic domain, providing hope that counseling can have a meaningful impact for these women. PMID- 17286064 TI - High prevalence of thyroid disease in patients with lichen sclerosus. AB - OBJECTIVE: To investigate the association between lichen sclerosus and thyroid disease in our patient population. STUDY DESIGN: This was a retrospective chart review of patients seen between January 1995 and September 2005 with biopsy proven lichen sclerosus. Charts were reviewed to assess the patients' history of thyroid disease. RESULTS: We identified 211 patients with biopsy-proven lichen sclerosus, 63 (29.9%) of whom had thyroid disease. In women <55 years old, 25 of 74 (33.8%) had thyroid disease; in women > or = 55 years old, 38 of 137 (27.7%) had thyroid disease. CONCLUSION: The prevalence of thyroid disease in our patients with biopsy-proven lichen sclerosus is almost 30% and is not dependent upon age. This prevalence is 5- to 30-fold greater than in the general population. PMID- 17286065 TI - Value of colposcopy in the diagnosis of candidiasis in patients with vulvodynia. AB - OBJECTIVE: To evaluate the value of colposcopy in the diagnosis of chronic vulvar candidiasis in patients presenting with vulvodynia. STUDY DESIGN: A prospective study of 460 patients presenting with vulvodynia over a 24-month period was undertaken. All patients underwent colposcopy of the vulva, which was regarded as positive if acetowhite lesions with central clearing with or without petechiae were present. Vulvar skin scrapings were taken for Candida culture on all patients. Those patients with positive colposcopic findings were treated with long-term oral antimycotic therapy irrespective of laboratory findings. RESULTS: Patients with positive colposcopic findings and positive cultures had a 93% rate of improvement in symptoms. Those with positive colposcopic findings and negative cultures also had a 60% rate of improvement. Thus, the overall improvement rate in patients with positive colposcopic findings (irrespective of culture results) was 76%. When colposcopy findings were negative, Candida cultures were also negative in 92% of patients. CONCLUSION: Colposcopy of the vulva can be a valuable triage tool in the assessment of patients with vulvodynia by detecting changes that are highly suspicious for the presence of chronic vulvar candidiasis. PMID- 17286066 TI - Extraosseous vulvar chondroma: a case report. AB - BACKGROUND: Extraosseous chondromas are cartilaginous tissue tumors with a nodular appearance on the hands and feet. There are reports of these tumors occurring on the knee, neck, back, liver and testis and in the oral cavity. Occurrence in the pelvis is generally rare. The origin is metaplastic and may be mesenchymal or subcelomic. Treatment is by surgery and requires removing the tumor with a safety margin. Recurrences are infrequent, and distant metastasis has never been reported. CASE: An 11-year-old girl was referred for a painless solid tumor located on the mons pubis. Surgical removal of the tumor with a safety margin was performed. Macroscopically, the tumor was shiny when cut open and yellowish. Microscopic examination revealed a very distinct cartilage-forming tumor compatible with extraosseous chondroma. Two years after the operation, the patient had no recurrence. CONCLUSION: Extraosseous chondroma is a rare benign tumor. Finding it in children is even less frequent, and localization in the vulvar region has never before been reported. This appears to be the first such report of this type of tumor in this region and age range. PMID- 17286067 TI - Decorin and chondroitin sulfate distribution in vulvar lichen sclerosus: correlation with distinct histopathologic stages. AB - OBJECTIVE: To characterize decorin and chondroitin sulfate (CS) expression in lichen sclerosus (LS). STUDY DESIGN: Thirty-one untreated vulvar LS lesions were biopsed, and hematoxylin-eosin-stained cases were graded according to Hewitt's classification. Immunohistochemistry was performed using antibodies directed against human decorin diluted 1:500 and CS diluted 1:200. The control group, made up of cutaneous fragments from vulvoperineal corrective surgeries or nymphoplasties, represented 22 patients. RESULTS: Decorin and CS were present at the LS hyaline zone in different moments of matrix modulation. In all Hewitt stages CS prevailed at the extracellular matrix in cases with a compact aspect of the hyaline zone, while decorin was seen only in areas of less compactness. Normal vulvar tissue revealed only the presence of CS in juxtaepithelial zones. No decorin immunoexpression was found in normal vulvar skin. CONCLUSION: Decorin and CS deposition in vulvar LS varies in the distinct histologic stages, which probably reflect the importance of these molecules in matricial remodeling in this disorder. Decorin may play an important role in cases of LS. PMID- 17286068 TI - Erosive vulvar lichen planus: retrospective review of characteristics and outcomes in 113 patients seen in a vulvar specialty clinic. AB - OBJECTIVE: To describe the characteristics of women diagnosed with erosive vulvar lichen planus and the outcome of treatment utilized by a single practitioner. STUDY DESIGN: A retrospective review of 113 women with erosive vulvar lichen planus. Data were abstracted, including demographic information, medical history, vulvar symptom scores and treatments utilized. Dyspareunia and vulvar symptom scores before and following treatment were compared. RESULTS: The mean age at presentation for women with lichen planus was 50 years. Comorbid medical and vulvar conditions were commonly noted. Sexually active women noted an improvement in dyspareunia symptom score and report of pain-free intercourse. Other symptoms described by women at the first visit included: burning (n = 76), itching (69), pain (43) and abnormal discharge (71). While these symptoms were significantly reduced at the final visit (p < 0.05 for each), the presence of vulvovaginal symptoms commonly waxed and waned in this group. Overall, 33% had resolution of symptoms, and 19% had improvement without resolution of symptoms. CONCLUSION: This cohort extends our understanding of the characteristics of women with erosive vulvar lichen planus and emphasizes its characteristically chronic course. While the recognition of erosive vulvar lichen planus may prevent unnecessary medical and surgical procedures, continued efforts to improve treatment should be investigated. PMID- 17286069 TI - Treatment of women in the United States with localized, provoked vulvodynia: practice survey of women's health physical therapists. AB - OBJECTIVE: To identify current practice trends of physical therapists in the U.S. treating women with localized, provoked vulvodynia (LPV). STUDY DESIGN: The Section on Women's Health conducted an Internet poll in July of 2005 inquiring about physical therapy care of women diagnosed with LPV. It queried clinicians' demographics, physician/clinician referral patterns, assessment/ treatment modalities and length of care. RESULTS: Nearly two-thirds reported >11 years of physical therapy experience, with 42% treating women with vulvodynia for > 6 years. Most referrals were from obstetrician/gynecologists. Assessment modalities used by > 70% included detailed history; assessment of posture, tension in the pelvic floor, pelvic girdle, associated pelvic structures and bowel/bladder function; digital sEMG/pEMG testing of the pelvic floor; hip, sacroiliac joints and spine mobility; strength testing of abdominals and lower extremities; and voiding diaries. Nearly 70% utilized exercise for the pelvic girdle and pelvic floor; soft tissue mobilization/myofascial release of the pelvic girdle, pelvic floor and associated structures; joint mobilization/manipulation; bowel/bladder retraining and help with contact irritants, dietary changes and sexual function. Typical care is 60-minute weekly sessions for 7-15 weeks. CONCLUSION: Sixty-three percent of physical therapists in the U.S. treating women with LPV have > 11 years of experience, with almost half treating women for > 6 years. Obstetrician/gynecologists are the largest referral source. Three quarters agree on 14 assessment tools, while more than two thirds agree on 11 treatments. Women are treated weekly for 1 hour, for 7-15 weeks. PMID- 17286070 TI - KTP-nd:YAG laser therapy for the treatment of vestibulodynia: a follow-up study. AB - OBJECTIVE: To evaluate the results of KTP-Nd:YAG laser therapy for the treatment of vestibulodynia. STUDY DESIGN: Retrospective review and follow-up mail survey of women with vestibulodynia who underwent laser treatment. Demographics, number of laser treatments and symptom severity prior to laser treatment (100-mm visual analog scale) were obtained from the medical record. The survey included questions regarding current sexual pain, sexual quality of life and satisfaction with treatment. RESULTS: Of41 treated women, 37 women were located and agreed to participate. The mean number of laser sessions was 2.81 (range, 1-8). The mean age was 32.9 years and mean follow-up, 2.8. Following laser treatment, most (24 of 37, 68%) subjects reported less pain with sexual intercourse. One subject reported more pain, while 29% (11 of 37) reported no change. Sixty percent (21 of 37) reported their sex lives to be more satisfying/pleasurable following laser treatment. Thirteen women (13 of 37, 35%) underwent vestibulectomy following laser therapy, and 2 subjects were treated with a laser after failed vestibulectomy. CONCLUSION: Most women with vestibulodynia treated with a KTP Nd:YAG laser achieve a reduction in sexual pain and improved sexual satisfaction without excisional therapy. PMID- 17286071 TI - Prevalence of vulvar pain in an urban, minority population. AB - OBJECTIVE: To determine the prevalence of vulvar pain in a large, urban, minority population. STUDY DESIGN: Women who presented to the University of Texas Southwestern Medical Center neighborhood clinic system for family planning services or gynecologic care were asked to complete a confidential questionnaire on the signs and symptoms of chronic vulvar pain. Responses were analyzed by ethnic group for the presence of vulvar pain. RESULTS: Three hundred twenty questionnaires were distributed, and 242 were completed,for a response rate of 75.6%. The population that completed the questionnaire (74% Hispanic, 20% African American, 5% Caucasian and 0.8% other) was similar in racial/ethnic distribution to the total population served in our health care system (66% Hispanic, 25% African American, 8% Caucasian and 1% other). Twenty-six (11%) women indicated they experienced vulvar pain. Sixteen women reported the start dates for the pain. Ten (63%) reported vulvar pain for more than 1 month. Of the 26 women reporting pain, the racial distribution was similar to that of our surveyed population (85% Hispanic, 11% African American, 4% Caucasian and 0% other). CONCLUSION: The prevalence of vulvar pain in this urban minority population was 11%. The prevalence of vulvar pain was similar among women of different racial/ethnic groups. PMID- 17286072 TI - Vulvodynia. Development of a psychosexual profile. AB - OBJECTIVE: To assess the psychosexual profile of vulvodynia patients, focusing on the age at onset and age distribution, and to analyze the impact of vulvodynia on the emotional, social and sexual well-being of this patient population. STUDY DESIGN: A retrospective review was performed of patient files consisting of questionnaires, psychometric tests, sexual history, electromyographic assessments and clinical notes. RESULTS: The highest prevalence of vulvodynia in this clinical sample occurred before the age of 25 years; 75% of the 744 patients were under the age of 34. A comparison of primary and secondary vulvodynia patients showed the average age at symptom onset to be 19.1 years for primary cases and 25.0 years for secondary cases. There were significant differences in duration of symptoms, age at first sexual intercourse and number of sexual partners, even when controlling for age (p < 0.001). Marriage provided an effective buffer against depression and anxiety. CONCLUSION: Vulvodynia can have an early onset and affect social relationships. Given the psychologic distress associated with vulvodynia, early diagnosis and treatment of the medical aspects are essential, as is focusing on the psychosexual implications of this pain syndrome. PMID- 17286073 TI - How leaders create and use networks. AB - Most people acknowledge that networking-creating a fabric of personal contacts to provide support, feedback, insight, and resources--is an essential activity for an ambitious manager. Indeed, it's a requirement even for those focused simply on doing their current jobs well. For some, this is a distasteful reality. Working through networks, they believe,means relying on "who you know" rather than "what you know"--a hypocritical, possibly unethical, way to get things done. But even people who understand that networking is a legitimate and necessary part of their jobs can be discouraged by the payoff--because they are doing it in too limited a fashion. On the basis of a close study of 30 emerging leaders, the authors outline three distinct forms of networking. Operational networking is geared toward doing one's assigned tasks more effectively. It involves cultivating stronger relationships with colleagues whose membership in the network is clear; their roles define them as stakeholders. Personal networking engages kindred spirits from outside an organization in an individual's efforts to learn and find opportunities for personal advancement. Strategic networking puts the tools of networking in the service of business goals. At this level, a manager creates the kind of network that will help uncover and capitalize on new opportunities for the company. The ability to move to this level of networking turns out to be a key test of leadership. Companies often recognize that networks are valuable, andthey create explicit programs to support them. But typically these programs facilitate only operational networking. Likewise, industry associations provide formal contexts for personal networking. The unfortunate effect is to give managers the impression that they know how to network and are doing so sufficiently. A sidebar notes the implication for companies' leadership development initiatives: that teaching strategic networking skills will serve their aspiring leaders and their business goals well. PMID- 17286074 TI - Becoming the boss. AB - Even for the most gifted individuals, the process of becoming a leader is an arduous, albeit rewarding, journey of continuous learning and self-development. The initial test along the path is so fundamental that we often overlook it: becoming a boss for the first time. That's a shame, because the trials involved in this rite of passage have serious consequences for both the individual and the organization. For a decade and a half, the author has studied people-particularly star performers-making major career transitions to management. As firms have become leaner and more dynamic, new managers have described a transition that gets more difficult all the time. But the transition is often harder than it need be because of managers' misconceptions about their role. Those who can acknowledge their misconceptions have a far greater chance of success. For example, new managers typically assume that their position will give them the authority and freedom to do what they think is best. Instead, they find themselves enmeshed in a web of relationships with subordinates, bosses, peers, and others, all of whom make relentless and often conflicting demands. "You really are not in control of anything, says one new manager. Another misconception is that new managers are responsible only for making sure that their operations run smoothly. But new managers also need to realize they are responsible for recommending and initiating changes-some of them in areas outside their purview-that will enhance their groups' performance. Many new managers are reluctant to ask for help from their bosses. But when they do ask (often because of a looming crisis), they are relieved to find their superiors more tolerant of their questions and mistakes than they had expected. PMID- 17286075 TI - Courage as a skill. AB - A division vice president blows the whistle on corruption at the highest levels of his company. A young manager refuses to work on her boss's pet project because she fears it will discredit the organization. A CEO urges his board, despite push back from powerful, hostile members, to invest in environmentally sustainable technology. What is behind such high-risk, often courageous acts? Courage in business, the author has found, seldom resembles the heroic impulsiveness that sometimes surfaces in life-or-death situations. Rather, it is a special kind of calculated risk taking, learned and refined over time. Taking an intelligent gamble requires an understanding of what she calls the "courage calculation": six discrete decision-making processes that make success more likely while averting rash or unproductive behavior. These include setting attainable goals, tipping the power balance in your favor, weighing risks against benefits, and developing contingency plans. Goals may be organizational or personal. Tania Modic had both types in mind when, as a young bank manager, she overstepped her role by traveling to NewYork--on vacation time and on her own money--to revitalize some accounts that her senior colleagues had allowed to languish. Her high-risk maneuver benefited the bank and gained her a promotion. Lieutenant General Claudia J. Kennedy weighed the risks and benefits before deciding to report a fellow officer who had plagiarized a research paper at a professional army school. In her difficult courage calculation, loyalty to army standards proved stronger than the potential discomfort and embarrassment of "snitching" on a fellow officer. When the skills behind courageous decision making align with a personal, organizational, or societal philosophy, managers are empowered to make bold moves that lead to success for their companies and their careers. PMID- 17286076 TI - The CEO's second act. AB - When a CEO leaves because of performance problems, the company typically recruits someone thought to be better equipped to fix what the departing executive couldn't--or wouldn't. The board places its confidence in the new person because of the present dilemma's similarity to some previous challenge that he or she dealt with successfully. But familiar problems are inevitably succeeded by less familiar ones, for which the specially selected CEO is not quite so qualified. More often than not, the experiences, skills, and temperament that yielded triumph in Act I turn out to be unequal to Act II's difficulties. In fact, the approaches that worked so brilliantly in Act I may be the very opposite of what is needed in Act II. The CEO has four choices: refuse to change, in which case he or she will be replaced; realize that the next act requires new skills and learn them; downsize or circumscribe his or her role to compensate for deficiencies; or line up a successor who is qualified to fill a role to which the incumbent's skills and interests are no longer suited. Hewlett-Packard's Carly Fiorina exemplifies the first alternative; Merrill Lynch's Stanley O'Neal the second; Google's Sergey Brin and Larry Page the third; and Quest Diagnostics' Ken Freeman the fourth. All but the first option are reasonable responses to the challenges presented in the second acts of most CEOs' tenures. And all but the first require a power of observation, a propensity for introspection, and a strain of humility that are rare in the ranks of the very people who need those qualities most. There are four essential steps executives can take to discern that they have entered new territory and to respond accordingly: recognition that their leadership style and approach are no longer working; acceptance of others' advice on why performance is faltering; analysis and understanding of the nature of the Act II shift; and, finally, decision and action. PMID- 17286078 TI - What to ask the person in the mirror. AB - Every leader gets off track from time to time. But as leaders rise through the ranks, they have fewer and fewer opportunities for honest and direct feedback. Their bosses are no longer monitoring their actions, and by the time management missteps have a negative impact on business results, it's usually too late to make course corrections that will set things right. Therefore, it is wise to go through a self-assessment, to periodically step back from the bustle of running a business and ask some key questions of yourself. Author Robert S. Kaplan, who during his 22-year career at Goldman Sachs chaired the firm's senior leadership training efforts and cochaired its partnership committee, identifies seven areas for self-reflection: vision and priorities, managing time, feedback, succession planning, evaluation and alignment, leading under pressure, and staying true to yourself. The author sets out a series of questions in each of the areas, illustrating the impact of self-assessment through vivid accounts of real executives. Although the questions sound simple, people are often shocked-even horrified- by their own answers. Executives are aware that they should be focusing on their most important priorities, for instance, but without stepping back to reflect, few actually know where they are allocating their time. Kaplan advocates writing down what you do every working hour for a week and checking how well your actions match up with your intentions. As for feedback, managers should ask themselves whether they're getting truthful evaluations from their subordinates. (In all likelihood, they aren't). It takes time and discipline to persuade your employees to tell you about your failings. PMID- 17286077 TI - Firing back: how great leaders rebound after career disasters. AB - Among the tests of a leader, few are more challenging-and more painful-than recovering from a career catastrophe. Most fallen leaders, in fact, don't recover. Still, two decades of consulting experience, scholarly research, and their own personal experiences have convinced the authors that leaders can triumph over tragedy--if they do so deliberately. Great business leaders have much in common with the great heroes of universal myth, and they can learn to overcome profound setbacks by thinking in heroic terms. First, they must decide whether or not to fight back. Either way, they must recruit others into their battle. They must then take steps to recover their heroic status, in the process proving, both to others and to themselves, that they have the mettle necessary to recover their heroic mission. Bernie Marcus exemplifies this process. Devastated after Sandy Sigoloff ired him from Handy Dan, Marcus decided to forgo the distraction of litigation and instead make the marketplace his batttleground. Drawing from his network of carefully nurtured relationships with both close and more distant acquaintances, Marcus was able to get funding for a new venture. He proved that he had the mettle, and recovered his heroic status, by building Home Depot, whose entrepreneurial spirit embodied his heroic mission. As Bank One's Jamie Dimon, J.Crew's Mickey Drexler, and even Jimmy Carter, Martha Stewart, and Michael Milken have shown, stunning comebacks are possible in all industries and walks of life. Whatever the cause of your predicament, it makes sense to get your story out. The alternative is likely to be long-lasting unemployment. If the facts of your dismissal cannot be made public because they are damning, then show authentic remorse. The public is often enormously forgiving when it sees genuine contrition and atonement. PMID- 17286079 TI - Changing of the old guard. With growing pressure on them to instigate healthcare reform, state hospital associations seek more dynamic leadership. AB - As state hospital associations increasingly feel the need to lead the charge for reform, there's been a wave of new chief executives at a number of groups. "The role of the state hospital association is in flux," says Dan Moen, left, chairman of the Massachusetts Hospital Association. "We're the incubators. Healthcare is moving toward that tipping point The confluence of issues and pressures is going to result in change". PMID- 17286080 TI - Many ideas, but little agreement. Employer groups call ideas too broad and too costly. PMID- 17286081 TI - Joint Commission under fire. GAO study shows possibility of conflicts: Stark. PMID- 17286082 TI - Rx for progress. Coalition offers e-prescribing service. PMID- 17286083 TI - Deluge of deals. Major players show their cards. PMID- 17286084 TI - Coalitions not coalescing. With national coverage plans failing to find consensus, states set to legislate. PMID- 17286085 TI - HCA sets new standard. Mergers and acquisitions hit the highest level since 2000, with a $33 billion leveraged buyout leading the pack. PMID- 17286086 TI - The next game of tag. Device ID system faces cost, uniformity challenges. PMID- 17286087 TI - By the numbers. Largest healthcare services mergers and acquisitions announced in 2006. U.S. deals ranked by deal's price. PMID- 17286088 TI - Evolutionary psychology: its programs, prospects, and pitfalls. AB - The emerging specialty of evolutionary psychology presents a challenge to mainstream psychology. It proposes that cognitive, notjust more fundamental, traits in humans are grounded in dedicated evolutionary programs. Specifically, it maintains that the common assumption in psychology-that the complexities of our psyches have been largely freed from evolutionary constraints and are instead based in a general learning capacity-is mistaken. The major premises of evolutionary psychology are examined in light of arguments and evidence presented by both supporters and detractors. Although some of these premises are well grounded, others are questionable and limit the development of the specialty and its integration into mainstream psychology. PMID- 17286089 TI - Modern application of evolutionary theory to psychology: key concepts and clarifications. AB - Darwinian selection has become the centerpiece of biology, and in the past few decades many psychologists and anthropologists have recognized the value of using an evolutionary perspective to guide their work. With a focus on evolved psychological mechanisms and associated information processing features, evolutionary psychology has risen as a compelling and fruitful approach to the study of human psychology and behavior. In this article we review the instrument of evolution: natural selection, the products of evolution, and the impact of evolutionary thinking on modern psychological science. We conclude that as prejudicial barriers are overcome, as more evolutionary psychological work is conducted, and as hypothesized psychological mechanisms are substantiated in other disciplines, evolutionary psychology will emerge as the metatheory for psychology. PMID- 17286090 TI - Phonetic-semantic mediated false recognition: does activation fail to spread? AB - Spoken word recognition involves brief activation of candidate words. Six experiments examined whether words semantically related to phonologically activated words would be falsely recognized. Experiments 1 and 2 involved homophones as test words; Experiment 3 used strong associates for the semantic mediation link. Experiment 4 approximated lists of "strong" converging associates. Experiment 5 expanded the real time needed for word identification by using a gating procedure during study. In Experiment 6, the goal was to create a more sensitive test by requiring participants to indicate which of two lures (mediated or control) was "most likely" to be new. Recognition errors were sensitive to separate phonetic and semantic stages in the mediated chain; however, there was little evidence of mediated false recognition, despite expectations derived from common models of spreading activation. PMID- 17286091 TI - Commission errors but not critical lures decrease when you have to pay a price for them. AB - Using the Deese-Roediger-McDermott paradigm, we explored the effect of monetary penalty on false memories. Participants were presented 6 15-word lists of semantic associates that all converged on a nonpresented critical lure. Next, half of the participants received a monetary reward (0.10 Euro; about $0.10) for each correctly recalled word, whereas they lost money (0.20 Euro; about $0.20) for each incorrect response. Compared with control participants who received a fixed financial compensation, participants in the experimental group reported fewer commissions (i.e., incorrect responses other than the critical lure). Number of hits and critical lures did not differ between the groups. PMID- 17286092 TI - Inductive inference or inductive behavior: Fisher and Neyman-Pearson approaches to statistical testing in psychological research (1940-1960). AB - The application of statistical testing in psychological research over the period of 1940-1960 is examined in order to address psychologists' reconciliation of the extant controversy between the Fisher and Neyman-Pearson approaches. Textbooks of psychological statistics and the psychological journal literature are reviewed to examine the presence of what Gigerenzer (1993) called a hybrid model of statistical testing. Such a model is present in the textbooks, although the mathematically incomplete character of this model precludes the appearance of a similarly hybridized approach to statistical testing in the research literature. The implications of this hybrid model for psychological research and the statistical testing controversy are discussed. PMID- 17286093 TI - Specificity in retraining craniocervical flexor muscle performance. AB - STUDY DESIGN: A multivariate repeated-measures independent-group study design. OBJECTIVES: To compare the effect of a craniocervical flexion exercise (CCFEx) program to that of a conventional cervical flexion exercise (CFEx) program in training isometric craniocervical flexor muscle performance. BACKGROUND: The craniocervical flexor muscles are important muscles of the cervical spine, as they have been shown to be impaired in persons with chronic neck pain. While both CCFEx and CFEx protocols have been advocated to train craniocervical flexor muscle performance, at present there is no consensus as to the most effective method. METHODS AND MEASURES: Fiftyfemales with chronic mild neck pain and disability status were randomly allocated into a 6-week program of either CCFEx (n = 27) or CFEx (n = 23). Isometric dynamometry measurements of craniocervical flexor muscle performance (maximal voluntary contraction, endurance at 50%'of maximal voluntary contraction) were recorded before and following the exercise program. Changes in craniocervical flexor muscle performance (pretraining posttraining) within and between exercise groups were analyzed with analysis of variance models. RESULTS: Both exercise interventions significantly improved isometric craniocervical flexor muscle performance (P<.02). No significant differences in improvement of muscle performance were observed between the2 exercise interventions. CONCLUSION: It appearsthat isometric craniocervical flexor muscle performance can be Strained with either a CCFEx protocol or a conventional CFEx protocol in patients with mild neck pain and disability. PMID- 17286094 TI - Safety, feasibility, and efficacy of negative work exercise via eccentric muscle activity following anterior cruciate ligament reconstruction. AB - STUDY DESIGN: Randomized, matched design. BACKGROUND: Optimal rehabilitation following anterior cruciate ligament reconstruction (ACL-R) requires safe and effective interventions. Negative work exercise (via eccentric muscle activity) has the potential to be highly effective at producing large quadriceps size and strength gains early after ACL-R. The purpose of this investigation was to evaluate the short-term safety and efficacy of adding a progressive negative work exercise program via eccentric (ECC) ergometry early after ACL-R. METHODS AND MEASURES: Beginning 3 weeks after ACL-R, 32 participants were randomly assigned into either a 12-week traditional (TRAD) or ECC exercise program. Safety was assessed by measuring knee pain, thigh pain, knee effusion, and knee stability prior to surgery and at 3,15, and 26 weeks after surgery. Efficacy was assessed by measuring negative work output during the 12-week training program and by measuring functional ability (ie, quadriceps peak torque, hopping distance, self reported functional ability and activity level scales) prior to surgery and 26 weeks after ACL-R. RESULTS: There were no significant differences between groups in measures of knee and thigh pain, effusion, or stability at any period after surgery. Negative work output increased systematically throughout training, while knee and thigh pain remained at relatively low levels. A significant group-by time interaction was observed for quadriceps peak torque, hopping distance, and activity level (P< or =.02). Quadriceps strength and hopping distance of the involved limb improved by a significantly greater amount in the ECC group compared to the TRAD group (P<.01). Activity level decreased to a lesser extent in the ECC group compared to the TRAD group (P =.02). CONCLUSIONS: Negative work via an ECC intervention was implemented safely after ACL-R. The addition of negative work exercise also induced superior short-term results in strength, performance, and activity level after surgery. PMID- 17286095 TI - Alterations in scapular kinematics in subjects with idiopathic loss of shoulder range of motion. AB - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To determine the effect of idiopathic loss of shoulder range of motion on scapular kinematics. BACKGROUND: Subjects with idiopathic loss of shoulder range of motion have difficulty performing activities of daily living. Previous investigations have focused on the glenohumeral component of shoulder complex motion. MATERIALS AND METHODS: Seventeen unilaterally impaired and 17 nonimpaired subjects. The 3-dimensional motion of the humerus, scapula, and trunk were measured withthe Fastrak electromagnetic motion-tracking system during humerus-to-trunk scapular plane elevation. An analysis of variance compared the impaired subjects noninvolved to the nonimpaired subjects' scapulae at 4 scapularplane elevation positions. A repeated-measures analysis of variance compared the impaired subjects' involved and noninvolved scapulae at 3 scapular plane elevation positions, and matched pairs t test compared peak elevation values. RESULTS: The between-group ANOVAs demonstrated no difference in anterior tipping, internal rotation, or upward rotation. The repeated-measures ANOVAs demonstrated no difference in anterior tipping or internal rotation and a position-by-side interaction in upward rotation. The involved-side scapulae were more upwardly rotated (7.7 degrees) at peak humerus-to-trunk scapular plane elevation. DISCUSSION AND CONCLUSION: The impaired subjects' noninvolved scapular kinematics were not significantly different than the nonimpaired subjects, but were significantly different than their involved scapulae. The upward rotation differences may be a substitution pattern used to accomplish functional elevation. PMID- 17286096 TI - Inhibition of hepatitis C IRES-mediated gene expression by 8-17 deoxyribozymes in human tissue culture cells. PMID- 17286097 TI - Inhibition of West Nile virus replication by short interfering RNAs. PMID- 17286098 TI - The role of the bacterial RNA polymerase beta subunit flexible flap domain in transcription termination. PMID- 17286099 TI - Geomagnetic stochastic control of vital activity. PMID- 17286100 TI - Catalytic properties of monoamine oxidase from the lamprey Lampetrafluviatilis liver. PMID- 17286102 TI - The key role of guanidine groups in the hormonal function of gonadotropin of the Russian sturgeon. PMID- 17286101 TI - Extracellular concentration of anticancer drugs that regulates their intracellular distribution and binding to DNA in cells with multidrug resistant phenotype. PMID- 17286103 TI - The effect of ionic strength on the reversible inhibition of acetylcholinesterase under the influence of thionephosphonates of different hydrophobicity. PMID- 17286105 TI - Detection of the products of acceptor interaction between orthophosphate and photoejected electron by EPR spectroscopy. PMID- 17286104 TI - A study of expression of hypoxanthine and cytokinin-like compounds in the presence of acetosyringone and dexamethasone in phototrophic purple bacteria and their sensor histidine kinases: biochemical and computer analysis. PMID- 17286106 TI - Fatty acid profiles of DNA-bound and whole-cell lipids of Pseudomonas aurantiaca drastically differ. PMID- 17286107 TI - The effect of dihydroquercetin on slow vacuolar channels. PMID- 17286108 TI - High-resolution NMR spectroscopy as a method of studying human biological fluids in normal state and pathology. PMID- 17286109 TI - Genetic differentiation of parthenogenetic lizards Darevskia rostombekowi (family Lacertidae) as determined using nuclear and mitochondrial DNA markers. PMID- 17286110 TI - Synergism of intercellular communications and involuntary movements in the formation of receptive fields and processing of visual signals at the level of retinal structural elements. PMID- 17286111 TI - Protective effect of the hexapeptide TGENHR on the TNF-induced death of HL-60 cells. PMID- 17286112 TI - Regulation of gene expression and activity of cytokinin oxidase in the roots of wheat seedlings by 24-epibrassinolide. PMID- 17286113 TI - The lipid fraction tightly bound to genomic DNA is determined in prokaryotes. PMID- 17286114 TI - Genetic risk factors of arterial hypertension: analysis of ischemic stroke patients from the Yakut ethnic group. PMID- 17286115 TI - Editorial essay: Molyneux's answer I. PMID- 17286116 TI - Incomplete figure perception and invisible masking. AB - The Gollin test (measuring recognition thresholds for fragmented line drawings of everyday objects and animals) has traditionally been regarded as a test of incomplete figure perception or 'closure', though there is a debate about how such closure is achieved. Here, figural incompleteness is considered to be the result of masking, such that absence of contour elements of a fragmented figure is the result of the influence of an 'invisible' mask. It is as though the figure is partly obscured by a mask having parameters identical to those of the background. This mask is 'invisible' only consciously, but for the early stages of visual processing it is real and has properties of multiplicative noise. Incomplete Gollin figures were modeled as the figure covered by the mask with randomly distributed transparent and opaque patches. We adjusted the statistical characteristics of the contour image and empty noise patches and processed those using spatial and spatial-frequency measures. Across 73 figures, despite inter subject variability, mean recognition threshold was always approximately 15% of total contour in naive observers. Recognition worsened with increasing spectral similarity between the figure and the 'invisible' mask. Near threshold, the spectrum of the fragmented image was equally similar to that of the 'invisible' mask and complete image. The correlation between spectral parameters of figures at threshold and complete figures was greatest for figures that were most easily recognised. Across test sessions, thresholds reduced when either figure or mask parameters were familiar. We argue that recognition thresholds for Gollin stimuli in part reflect the extraction of signal from noise. PMID- 17286117 TI - Effects of image background on spatial-frequency thresholds for face recognition. AB - A great deal of work has been devoted to the question of which spatial frequencies, if any, are optimal for various visual tasks, such as face and object recognition. However, to date these studies have all been carried out with stimuli set against a uniform background. It is possible that this type of stimulus does not produce ecologically valid results. The natural world in which visual tasks normally take place involves a great deal of luminance variation and distracting visual structure, which may alter the spatial frequencies necessary for a task. We conducted two experiments that examined the effects of image background on the spatial-frequency thresholds (50% maximum of a low-pass or high pass Butterworth filter) for face recognition by the psychophysical methods of adjustment and constant stimuli. In both experiments we found no significant difference in spatial-frequency thresholds between uniform-grey backgrounds and natural-scene backgrounds, and only minor differences between uniform-grey backgrounds and fractal noise backgrounds. This suggests that results obtained with uniform backgrounds are ecologically valid and that background effects, if they exist, are small. PMID- 17286118 TI - The perception of unfamiliar faces and houses by chimpanzees: influence of rotation angle. AB - The inversion effect, or impaired recognition of upside-down faces, is used as evidence supporting the configural processing of faces. Human studies report a linear relationship between face-discrimination performance and orientation, such that recognition is more difficult as faces are rotated away from their typical viewpoint. Previous studies on chimpanzees also support a configural bias for processing faces, particularly faces for which subjects have developed expertise. In the present study, we examined the influence of expertise and rotation angle on the visual perception of faces in chimpanzees. Six subjects were presented with unaltered and blurred conspecific faces and houses in five orientation angles. A computerized paradigm was used to further delineate the nature of configural face processing in this species. The data were consistent with those reported in humans: chimpanzees showed a significant linear impairment when discriminating conspecific faces as they rotated away from their upright orientation. No inversion effect was observed for discriminations involving houses. Thus, chimpanzees, like humans, show a face-specific inversion effect that is linearly affected by angle of orientation, suggesting that their visual processing of faces is strongly influenced by the extraction of configural cues and closely resembles the perceptual strategies of humans. PMID- 17286119 TI - Making heads turn: the effect of familiarity and stimulus rotation on a gender classification task. AB - Recent work has demonstrated that facial familiarity can moderate the influence of inversion when completing a configural processing task. Here, we examine whether familiarity interacts with intermediate angles of orientation in the same way that it interacts with inversion. Participants were asked to make a gender classification to familiar and unfamiliar faces shown at seven angles of orientation. Speed and accuracy of performance were assessed for stimuli presented (i) as whole faces and (ii) as internal features. When presented as whole faces, the task was easy, as revealed by ceiling levels of accuracy and no effect of familiarity or angle of rotation on response times. However, when stimuli were presented as internal features, an influence of facial familiarity was evident. Unfamiliar faces showed no increase in difficulty across angle of rotation, whereas familiar faces showed a marked increase in difficulty across angle, which was explained by significant linear and cubic trends in the data. Results were interpreted in terms of the benefit gained from a mental representation when face processing was impaired by stimulus rotation. PMID- 17286120 TI - Recognition of biological motion from blurred natural scenes. AB - Biological-motion perception can be regarded as a template-matching process. We are concerned with the visual cues in this template. Biological-motion perception is usually studied with point-light displays similar to the point-light displays invented by Johansson (1973 Perception and Psychophysics 14 201 - 211). These stimuli are in some ways abstract. In order to use more natural stimuli, we recorded movies of different actions in natural scenes. By blurring the scenes we modified the visual cues, particularly the local form and motion information. Observers were asked to identify the action portrayed. Our results demonstrate that templates for biological-motion recognition combine global form and motion cues. Reductions of local form and local motion information by blurring can be compensated by global form change and global motion. Local motion information is also used for segmentation. PMID- 17286121 TI - Scene recognition following locomotion around a scene. AB - Effects of locomotion on scene-recognition reaction time (RT) and accuracy were studied. In experiment 1, observers memorized an 11-object scene and made scene recognition judgments on subsequently presented scenes from the encoded view or different views (ie scenes were rotated or observers moved around the scene, both from 40 degrees to 360 degrees). In experiment 2, observers viewed different 5 object scenes on each trial and made scene-recognition judgments from the encoded view or after moving around the scene, from 36 degrees to 180 degrees. Across experiments, scene-recognition RT increased (in experiment 2 accuracy decreased) with angular distance between encoded and judged views, regardless of how the viewpoint changes occurred. The findings raise questions about conditions in which locomotion produces spatially updated representations of scenes. PMID- 17286123 TI - Synesthetically induced colors evoke apparent-motion perception. AB - Synesthesia is a condition in which certain otherwise normal individuals see colors when they hear tones, or, when they look at black-and-white numbers, each number is tinged with a specific color (eg 5 is red and 2 is green). We constructed a display in which a random matrix of 5s had a vertical column of 2s 'embedded' in it. This was shown in frame 1 of a movie, followed by a similar display in frame 2 in which the element locations were uncorrelated but the bar as a whole was shifted horizontally. When normal subjects viewed the display, they just saw random jitter or twinkle; there was no impression of a bar moving horizontally. But, when our subject (JC) who had grapheme-color synesthesia viewed the display, he reported seeing a bar moving left or right depending on the trial. We conclude that, in at least some subjects, a synesthetically induced color that does not exist on the retina can nonetheless influence motion perception. PMID- 17286122 TI - Demonstrations of spatiotemporal integration and what they tell us about the visual system. AB - Five sets of displays are presented on the journal website to be viewed in conjunction with the text. We concentrate on the factors that give rise to the integration and disruption of the direction of apparent motion in two-dimensional and three-dimensional space. In the first set of displays we examine what factors contribute to the integration and disruption of apparent motion in the Ramachandran/Anstis clustered bistable quartets. In the second set we examine what factors give rise to the perception of the direction of motion in rotating two-dimensional wheels and dots. In the third and fourth sets we examine how the depth cues of shading and disparity contribute to the perception of apparent motion of opaque displays, and to the perception of rotating unoccluded displays, respectively. In the fifth set we examine how the depth cue of motion parallax influences the perception of apparent motion. Throughout, we make inferences about the roles which various parallel pathways and cortical areas play in the perceptions produced by the displays shown. PMID- 17286124 TI - The crossed-hands deficit in tactile temporal-order judgments: the effect of training. AB - Several recent studies have shown that judgments of temporal order for tactile stimuli presented to the two hands are greatly affected by crossing the hands. The size of the threshold for judging temporal order may be up to four times larger with the hands crossed as compared to the hands uncrossed. The results from these recent studies suggest that with crossed hands, contrary to many situations involving the integration of tactile and proprioceptive information, subjects have difficulty in adjusting their perception of tactile inputs to correspond with the spatial positions of the hands. In the present study we examined the effect of training in judging temporal order on the size of this crossed-hands deficit--the difference in the thresholds for temporal-order judgments when the hands are crossed and uncrossed. All training procedures produced significant declines in the size of the deficit. With training, the difference between crossed-hands and uncrossed-hands temporal-order thresholds dropped from several hundred milliseconds to as little as 19 ms. A group of percussionists with experience in playing with crossed hands showed the same crossed-hands effects as non-musicians. The results were consistent in showing that the crossed-hands deficit was never completely eliminated but was greatly reduced with training. The implication is that subjects are able to adjust to the crossed-hands posture with modest amounts of training. The results are discussed in terms of the explanations that have been offered for the crossed-hands deficit. PMID- 17286125 TI - A new set of illusions--the dynamic luminance-gradient illusion and the breathing light illusion. AB - A novel set of illusions that break brightness constancy and size constancy at the same time is reported. The illusions occur when observers move towards or away from these patterns. Many variations of these phenomena and a possible explanation are discussed. PMID- 17286126 TI - Surgical extraction of impacted teeth in a dog. PMID- 17286127 TI - Evaluation of subgingival bacteria in the dog and susceptibility to commonly used antibiotics. AB - The aim of the present investigation was to evaluate the subgingival aerobic and anaerobic flora of 13 dogs with periodontal disease and the susceptibility of these bacteria to antibiotics currently approved in Italy for treatment of canine infections. Of the anaerobic bacteria, Bacteroides fragilis was most frequently isolated, followed by Peptostreptococcus + Porphyromonas gingivalis and Prevotella intermedia. Of the aerobic bacteria, alpha-hemolytic Streptococcus was most frequently isolated, often associated with Escherichia coli or Pasteurella multocida. Resistance of anaerobic and aerobic bacteria to various antibiotics was generally high. Anaerobic bacteria appeared to be susceptible to amoxicillin + clavulanic acid, doxycycline, and erythromycin; aerobic bacteria appeared to be susceptible to amoxicillin + clavulanic acid, erythromycin, gentamycin, and sulfa trimethoprim. Bacteroides fragilis was resistant to all of the antibiotics tested. The emerging worldwide problem of bacterial resistance to antibiotics resulting from overuse and misuse of antibiotics is discussed. PMID- 17286128 TI - The effect of occlusal equilibration on sport horse performance. AB - The objective of this study was to investigate the effect of routine dental occlusal equilibration treatment on dressage horse performance. Sixteen horses (11 treated; 5 untreated) ridden by a single rider performed a standardized dressage test twice and were scored by two experienced dressage judges according to recognized movements and rider cues. All horses were sedated and a full-mouth speculum was used to facilitate a complete oral examination. Treated horses had dental equilibration performed using a motorized dental instrument. The horses performed a second test 48-hours after dental equilibration, exactly as the baseline test, with the judges and rider blinded as to treatment group. The total test score as well as the individual movement scores were evaluated for equality of variance and statistical tests were applied to determine the influence of treatment. There was no significant improvement in the test score of horses that had received occlusal equilibration. PMID- 17286129 TI - Diagnosis and management of Wegener's granulomatosis in a dog. AB - A four-year-old maele/neutered mixed-breed dog was prsented for severe, multifocal, proliferative gingivitis. Histopathologic examination of incisional biopsies supported a diagnosis of Wegener's granulomatosis, an autoimmune vasculitis previously unreported in the veterinary literature. Diagnostic investigations for infectious, neoplastic, or other inflammatory conditions all provided negative results. Management with a combination of immunosuppressive agents resulted in complete resolution and remission of the presenting lesions and associated clinical signs. PMID- 17286130 TI - Treatment of vertical bone loss in a dog. PMID- 17286131 TI - Split palatal U-flap for repair of caudal palatal defects. PMID- 17286133 TI - Patient involvement. Criticism for public consultation bill. PMID- 17286132 TI - NHS and councils could be placed under 'single regime'. PMID- 17286134 TI - PCTs fight UCLH over data validity. PMID- 17286135 TI - National IT programme. Crucial decision looms on the future of the IT programme. PMID- 17286136 TI - Powering reforms. PMID- 17286137 TI - How doctors learned to start loving data. PMID- 17286138 TI - Barometer. Acute trusts Jan 2007. PMID- 17286139 TI - Roundtable discussion. Wish they weren't here? PMID- 17286140 TI - Primary care. Information stations. PMID- 17286141 TI - Commissioning. Faster, stronger, better. PMID- 17286142 TI - What direction for community services? PMID- 17286143 TI - Face up to a public-private future. PMID- 17286144 TI - A LINk to real engagement. PMID- 17286145 TI - Leadership. The quest for the holy grail. PMID- 17286146 TI - DEHP, bis(2)-ethylhexyl phthalate, alters gene expression in human cells: possible correlation with initiation of fetal developmental abnormalities. AB - Diethylhexylphthalate (DEHP) is a widely distributed phthalate, to which humans are exposed to due to its variety of commercial and manufacturing uses. As a plasticiser, it is found in a wide number of products, and metabolites of DEHP have been detected in urine samples from a high percentage of the people screened for phthalates. We utilised DNA microarray analysis to evaluate DEHP for gene expression disrupting activity using the human cell line MCF-7, and found that DEHP significantly dysregulated approximately 34% of the 2400 genes spotted on the NEN2400 chip we used. The results suggest that DEHP, a known estrogen agonist and probable androgen antagonist, alters the expression of a number of genes, many of which are critical for fetal development. Down-regulation of two genes, FGD1 and PAFAH1B1, related in that both are essential for fetal brain development, was corroborated using quantitative real time PCR. These studies show DEHP to be a highly effective human gene expression-altering chemical, and that, at appropriate concentrations, it has the possibility of altering fetal central nervous system development, resulting in the birth defects lissencephaly and/or faciodigitogenital dysplasia. PMID- 17286147 TI - Alteration of hepatic cells glucose metabolism as a non-cholinergic detoxication mechanism in counteracting diazinon-induced oxidative stress. AB - The aim of this study was to evaluate effects of acute exposure to various doses of diazinon, a widely used synthetic organophosphorus (OP) insecticide on plasma glucose, hepatic cells key enzymes of glycogenolysis and gluconeogenesis, and oxidative stress in rats. Diazinon was administered by gavage at doses of 15, 30 and 60 mg/ kg. The liver was perfused and removed under anaesthesia. The activities of glycogen phosphorylase (GP), phosphoenolpyruvate carboxykinase (PEPCK), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were analysed in liver homogenate. Administration of diazinon (15, 30 and 60 mg/kg) increased plasma glucose concentrations by 101.43% (P = 0.001), 103.68% (P = 0.000) and 160.65% (P = 0.000) of control, respectively. Diazinon (15, 30 and 60 mg/kg) increased hepatic GP activity by 43.5% (P = 0.05), 70.3% (P = 0.00) and 117.2% (P = 0.02) of control, respectively. In addition, diazinon (30 and 60 mg/kg) increased hepatic PEPCK by 77.3% (P = 0.000) and 93.5% (P = 0.000) of control, respectively. Diazinon (30 and 60 mg/kg) decreased liver TAC by 38% (P = 0.046) and 48% (P = 0.000) of control, respectively. Also diazinon (30 and 60 mg/kg) increased hepatic cell liver lipid peroxidation by 77% (P = 0.05) and 280% (P = 0.000) of control. The correlations between plasma glucose and hepatic cells TBARS (r2 = 0.537, P = 0.02), between plasma glucose and ChE activity (r2 = 0.81, P = 0.049) and between plasma glucose and hepatic cells GP activity (r2 = 0.833, P = 0.04) were significant. It is concluded that the liver cells are a site of toxic action of diazinon. Diazinon increases glucose release from liver into blood through activation of glycogenolysis and gluconeogenesis as a detoxication non-cholinergic mechanism to overwhelm diazinon-induced toxic stress. The results are in accordance with the hypothesis that OPs are a predisposing factor of diabetes. PMID- 17286148 TI - Protective effects of Gingko biloba on thioacetamide-induced fulminant hepatic failure in rats. AB - Gingko biloba (GB) has antioxidant and platelet-activating factor (PAF) antagonistic effects. We investigated the protective effects of GB on thioacetamide (TAA)-induced fulminant hepatic failure in rats. Fulminant hepatic failure was induced in treatment groups by three intraperitoneal (ip) injections of TAA (350 mg/kg) at 24-hour intervals. Treatments with GB (100 mg/kg per day, orally) and N-acetylcysteine (20 mg/kg twice daily, sc) were initiated 48 hours prior to TAA administration. The liver was removed for histopathological examinations. Serum and liver thiobarbituric acid-reactive substance (TBARS) levels were measured for assessment of oxidative stress. Liver necrosis and inflammation scores and serum and liver TBARS levels were significantly higher in the TAA group compared to the control group (P < 0.001, < 0.001, 0.001, < 0.001, respectively). Liver necrosis and inflammation scores and liver TBARS levels were significantly lower in the GB group compared to the TAA group (P < 0.001, < 0.001 and 0.01, respectively). GB ameliorated hepatic damage in TAA-induced fulminant hepatic failure. This may be due to the free radical-scavenging effects of GB. PMID- 17286149 TI - Evaluation of the effects of hydrophilic organic solvents on CYP3A-mediated drug drug interaction in vitro. AB - This study evaluated the effects of the commonly used hydrophilic organic solvents, acetonitrile, methanol, ethanol, 1-propanol, dimethyl sulfoxide (DMSO), N,N-dimethylformamide, polyethylene glycol and propylene glycol, on CYP3A in pooled human liver microsomes, using testosterone and midazolam as substrates. Furthermore, we examined the modulation effect of organic solvents on CYP3A inhibition by ketoconazole. Testosterone 6beta-hydroxylation activity was potently inhibited in the presence of DMSO and 1-propanol in a concentration dependent manner. Midazolam 1'-hydroxylation activity, however, was weakly inhibited only by 1% of DMSO, the highest concentration used in this study. Moreover, the potency of ketoconazole to inhibit CYP3A activities was variable, depending on the organic solvent used as a dissolving solvent for ketoconazole. Our data indicate that each organic solvent had an effect on CYP3A4 activity, evaluated by both substrates with different magnitudes. Furthermore, it was shown that the effects of organic solvents on CYP3A activity are substrate-dependent. The present study also shows that methanol had little effect on either substrate. PMID- 17286150 TI - Acute effects of exposure to vapours of dioxane in humans. AB - Information on the acute effects associated with the handling of 1,4-dioxane is sparse. Our aim was to evaluate the acute effects of 1,4-dioxane vapours. In a screening study, six healthy volunteers rated symptoms on a visual analogue scale (VAS), while exposed to stepwise increasing levels of 1,4-dioxane, from 1 to 20 ppm. The initial study indicated no increased ratings at any of the exposure levels; we decided to use 20 ppm (72 mg/m3) as a tentative no observed adverse effect level (NOAEL). In the main study, six female and six male healthy volunteers were exposed to 0 (control exposure) and 20 ppm 1,4-dioxane vapour, for 2 hours at rest. The volunteers rated 10 symptoms on VAS before, during, and after the exposure. Blink frequency was monitored during exposure. Pulmonary function, and nasal swelling, was measured before, and at 0 and 3 hours after exposure. Inflammatory markers in plasma (C-reactive protein, and interleukin-6) were measured before and at 3 hours after exposure. In conclusion, exposure to 20 ppm 1,4-dioxane for 2 hours did not significantly affect symptom ratings, blink frequency, pulmonary function, nasal swelling, or inflammatory markers in the plasma of the 12 volunteers in our study. PMID- 17286151 TI - Suicide attempt with clopidogrel. AB - We report the case of a 49-year-old male who took an overdose of 1650 mg of clopidogrel with suicidal intent. The patient developed abnormalities of platelet aggregation, but never developed symptoms. Clopidogrel is a commonly prescribed drug. Reports of overdose of clopidogrel were very rarely reported in the literature. PMID- 17286152 TI - Olanzapine overdose is associated with acute muscle toxicity. AB - Olanzapine is an atypical antipsychotic that is reported to cause myopathy and raised creatine kinase (CK) levels. The prevalence and severity of acute myopathy after deliberate olanzapine ingestion are unclear. Therefore, we reviewed case notes from 64 consecutive patients admitted to our institution after olanzapine overdose. Overall, serum CK was higher than five times the upper limit of normal in 17% of patients. The prevalence of raised CK values was positively correlated with the stated quantity of olanzapine ingested, suggesting a dose-dependent relationship for acute muscle toxicity. There was an apparent delay of 12 hours or more between olanzapine ingestion and the occurrence of maximum CK. Despite the high prevalence of acute muscle toxicity after olanzapine ingestion, none of the patients developed renal failure. PMID- 17286153 TI - More advances for dermatology patients. PMID- 17286154 TI - A comprehensive management guide for atopic dermatitis. PMID- 17286156 TI - An overview of Medicare reimbursement regulations for advanced practice nurses. PMID- 17286155 TI - Allergens of new and emerging significance. PMID- 17286157 TI - What's your assessment? Bullous pemphigoid. PMID- 17286158 TI - Treatment of cutaneous T-cell lymphoma/mycosis fungoides. AB - The cause of mycosis fungoides is unknown and, with the possible exception of very early stage disease, no cure is available. Fortunately, patients with MF have a number of therapeutic options and partial and complete remissions are achievable. Because it is not curable, the burden for patients with this disease involves the need for lifelong therapy and monitoring, and meticulous skin care. Despite its indolent nature in most individuals, the disease has a tremendous psychological impact, not only because of the visible nature of the skin lesions, but also due to the rarity of the disease and its chronicity. Knowledge of this disease, therapeutic options, and expectations of therapy will enhance care of patients afflicted with mycosis fungoides. Ongoing research provides hope that in the future, therapy to induce long-lasting remission, or even cure, will become available. Since the submission of this manuscript, vorinostat (Zolinza), an orally administered histone inhibitor, has been FDA approved for treating skin manifestations in patients with CTCL. PMID- 17286159 TI - The results and side effects of systemic isotretinoin treatment in 100 patients with acne vulgaris. PMID- 17286160 TI - 'It hurts when I walk:' venous stasis disease--differential diagnosis and treatment. AB - Venous stasis disease represents 70% to 90% of lower-extremity ulcers treated. Venous hypertension brought about by inadequate venous return and defective valvular systems is the main culprit. Positive outcomes in patient care can be achieved by an ongoing partnership between the health care provider and the patient to control the disease and its effects. Appropriate assessment and management require a long-term commitment by a multidisciplinary team to encourage and enhance patient compliance and to prevent recurrence. In the next issue: arterial disease. PMID- 17286161 TI - Basal cell carcinoma. PMID- 17286163 TI - Scabies. PMID- 17286162 TI - Atopic dermatitis. PMID- 17286164 TI - Authentic leadership. AB - There is leadership, and then there is authentic leadership. If you are not willing to engage from your heart, to passionately work to create a greater quality of work life for front-line staff every day, and to push yourself to the ultimate limit to make that happen, you might be a leader, but you will not be perceived as an authentic leader. Authentic leaders love, challenge people to do what they didn't believe was possible, and generate the energy to make the impossible possible by their passion for their people, their patients, and for doing the right thing. Thankfully, there are leaders who are willing to live on the edge, model their love, and inspire people to change the world. Will you be one of them? PMID- 17286165 TI - Extreme size and sequence variation in the ITS rDNA of Bremia lactucae. AB - Bremia lactucae Regel (Chromista, Peronosporaceae) is an economically destructive pathogen, which causes downy mildew disease on lettuce (Lactuca sativa L.) worldwide. The ribosomal internal transcribed spacer (ITS) of Bremia lactucae isolates was analyzed for the first time. The ITS region of lettuce downy mildew was observed to have a size of 2458 bp; thereby, having one of the longest ITS sizes recorded to date. The majority of the extremely large sized ITS2 length of 2086 was attributed to the additional presences of nine repetitive elements with lengths of 179-194 bp, which between them shared the low homology of 48-69%. Comparison of the ITS2 sequences with the B. lactucae isolates from other host plants showed that isolates present on Lactuca sativa were distinct from those on L. indica var. laciniata, as well as Hemistepta and Youngia. We suggest the high degree of sequence heterogeneity exhibited in the ITS2 region of B. lactucae may warrant the specific detection and diagnosis of this destructive pathogen or its division into several distinct species. PMID- 17286167 TI - A forecast analysis on fertilizers consumption worldwide. AB - This study aimed to make a review and forecast on fertilizers consumption worldwide in order to provide basal data for the decision-making of fertilizers production and for the environmental impact assessment of fertilizers application. It was found that fertilizers consumption was dependent on human population and the increase of fertilizers consumption was mainly resulted from expansion of human population. The univariate linear model, y=a+rx(t), where y is the fertilizers consumption, x(t) is the total human population at year t, r is the annual fertilizers consumption per capita, was used to fit historical data of fertilizers consumption, and the forecasts during 2010 to 2030 were given in detail. Model analysis showed that world's per capita annual consumption of total fertilizers, nitrogenous fertilizers, phosphate fertilizers, and potash fertilizers, were 34.6, 24.4, 6.6, and 3.7 kg, respectively. Per capita annual consumption of total fertilizers for Asia, Africa, Caribbean, Oceania, North & Central America, Europe, and South America were 38.8, 5.9, 6.8, 114.0, 62.9, 0.9, and 43.6 kg, respectively. Compared to the current level, the world's total fertilizers consumption would reach 226,150,381 Mt by 2030, an increase of 32.1% against current level. Worldwide consumption of nitrogenous fertilizers, phosphate fertilizers, and potash fertilizers would reach 141,800,601, 50,961,129, and 33,388,650 Mt by 2030, increasing 37.5, 25.8, and 21.2% based on current levels. Consumption of total, nitrogenous, phosphate, and potash fertilizers in Asia and Africa would increase 54 to 55% and 40 to 60% by 2030, respectively. Total fertilizers consumption in North & Central America would see an increase of 39.4% by 2030, and in South America and Oceania it would increase by 30.9 and 64.7%, respectively. By 2030, Caribbean's consumption for total fertilizers would increase 2.8%. Europe's total fertilizers consumption was forecast to continuously decline and would have a decrease of 2.4% by 2030. Annual relative growths of consumption of total fertilizers, nitrogenous fertilizers, phosphate fertilizers, and potash fertilizers for the world, Africa, Asia, and South America were forecast to decrease in the forecast period. For North & Central America, annual relative growths of consumption of total fertilizers and nitrogenous fertilizers would decrease and the others would increase annually by 2030. Annual relative growths of consumption of total fertilizers, phosphate fertilizers, and potash fertilizers for Oceania were forecast to rise annually by 2030. Europe's annual relative growths of consumption of total fertilizers and potash fertilizers would decrease in the future. PMID- 17286166 TI - Characterization of AFLAV, a Tf1/Sushi retrotransposon from Aspergillus flavus. AB - The plasmid, pAF28, a genomic clone from Aspergillus flavus NRRL 6541, has been used as a hybridization probe to fingerprint A. flavus strains isolated in corn and peanut fields. The insert of pAF28 contains a 4.5 kb region which encodes a truncated retrotransposon (AfRTL-1). In search for a full-length and intact copy of retrotransposon, we exploited a novel PCR cloning strategy by amplifying a 3.4 kb region from the genomic DNA of A. flavus NRRL 6541. The fragment was cloned into pCR 4-TOPO. Sequence analysis confirmed that this region encoded putative domains of partial reverse transcriptase, RNase H, and integrase of the predicted retrotransposon. The two flanking long terminal repeats (LTRs) and the sequence between them comprise a putative full-length LTR retrotransposon of 7799 bp in length. This intact retrotransposon sequence is named AFLAV (A. flavus Retrotransposon). The order of the predicted catalytic domains in the polyprotein (Pol) placed AFLAV in the Tf1/sushi subgroup of the Ty3/gypsy retrotransposon family. Primers derived from AFLAV sequence were used to screen this retrotransposon in other strains of A. flavus. More than fifty strains of A. flavus isolated from different geological origins were surveyed and the results show that many strains have extensive deletions in the regions encoding the capsid (Gag) and Pol. PMID- 17286168 TI - Evaluation for sustainable land use in mountain areas of Northwestern Yunnan Province, China. AB - As an important component of sustainable development in mountain areas, evaluation for sustainable land use is always one of the hotpots of researches on sustainable development. Traditional evaluation for sustainable land use mainly focuses on the sustainability of land use model and biological production on temporal scale, and overlooks the effects of land use patterns on the sustainability, while landscape ecology can be a good help to realize the spatial analysis of sustainable land use. In this study, a synthetic evaluation indexes system for sustainable land use was constructed through the application of landscape metrics. Taking Yongsheng County of Yunnan Province, China as a case study, a series of quantitative evaluation were conducted in 1996, 1999 and 2001, to monitor the temporal dynamics of regional land use sustainability. Two indicators, contributing amount of indexes, and obstacle amount of indexes, were also set up to ascertain the significance of all the evaluation indexes to the evaluation results. The results showed that, in the study phases, the land use sustainability of the whole county had been low with a stable but great spatial difference, and great changes took place in regional land use system in 1999 with the deviation from the aim of sustainable land use. It also showed that, the most important indexes contributing for the land use sustainability in the study period, were the indexes of population density and land use degree, followed by the index of landscape diversity and cropping index. And the most important indexes counteracting the land use sustainability were the indexes of per unit area total production value of industry and agriculture, per unit area yield of cereal crops, landscape fragmentation, followed by the indexes of per unit area yield of economic crops and fertilizer consume per unit area. PMID- 17286169 TI - Sub-soil contamination due to oil spills in zones surrounding oil pipeline-pump stations and oil pipeline right-of-ways in Southwest-Mexico. AB - Oil spills due to oil pipelines is a very frequent problem in Mexico. Petroleos Mexicanos (PEMEX), very concerned with the environmental agenda, has been developing inspection and correction plans for zones around oil pipelines pumping stations and pipeline right-of-way. These stations are located at regular intervals of kilometres along the pipelines. In this study, two sections of an oil pipeline and two pipeline pumping stations zones are characterized in terms of the presence of Total Petroleum Hydrocarbons (TPHs) and Polycyclic Aromatic Hydrocarbons (PAHs). The study comprehends sampling of the areas, delimitation of contamination in the vertical and horizontal extension, analysis of the sampled soils regarding TPHs content and, in some cases, the 16 PAHs considered as priority by USEPA, calculation of areas and volumes contaminated (according to Mexican legislation, specifically NOM-EM-138-ECOL-2002) and, finally, a proposal for the best remediation techniques suitable for the contamination levels and the localization of contaminants. PMID- 17286170 TI - Freshwater crayfish Astacus leptodactylus (Eschscholtz, 1823) accumulates and depurates copper. AB - Cu accumulation and depuration in various tissues of the crayfish Astacus leptodactylus was investigated. Adult specimens were exposed to 0.5, 2.5 and 5.0 mg Cu/L under static conditions for three weeks. At the end of the 3rd week the specimens were divided into three groups and left in dechlorinated water for either 1, 2 or 3 weeks for depuration. After 7, 14 and 21 days, four crayfish from each group were instantaneously sacrificed. All crayfish were dissected into their hepatopancreas, gill, abdominal muscle and exoskeleton tissues for evaluation of Cu accumulation in each. The following accumulation pattern was obtained in decreasing order; hepatopancreas > gills > exoskeleton > abdominal muscles with values of 94.13, 84.86, 66.13 and 11.43 mg/L, respectively. The observed Cu depuration throughout the study was found to be time-dependent. Based on the present work we conclude that crayfish has a great potential for rapid accumulation and depuration of Cu in fresh water. PMID- 17286171 TI - Exports of dissolved ammonium (NH(4)(+)) during storm events across multiple catchments in a glaciated forested watershed. AB - Storm event exports of dissolved NH(4)(+) were explored for multiple events in the Point Peter Brook watershed (PPBW), a glaciated, forested watershed located in Western New York, USA. Investigations were performed across four catchments (1.6-696 ha) with varying topography and the extent of surface-saturated areas. While wetland and riparian waters were important sources of NH(4)(+) during non storm periods, throughfall and litter leachate were the dominant contributors of NH(4)(+) during storm events. Ammonium concentrations in catchment discharge displayed a sinusoidal seasonal pattern with a maximum during early spring (March) and a minimum in late summer (August-September). Storm event concentrations of NH(4)(+) in streamflow were much greater than baseflow values and showed a consistent temporal pattern with an increase in concentrations on the hydrograph rising limb, a peak at or before the discharge peak, followed by a decline in concentrations. Storm event patterns of DON were similar to NH(4)(+) while the patterns of [Formula: see text]differed from NH(4)(+) for the summer and fall events. The storm event expression of NH(4)(+) was attributed to throughfall and throughfall-mediated leaching of the litter layer. The reactive behavior of NH(4)(+) precluded its use in an end member mixing model (EMMA) for predicting streamflow concentrations. While concentrations of NH(4)(+) in precipitation and streamflow were high for the spring events, exports of NH(4)(+) in streamflow were highest for the large and intense storm events. Baseflow NH(4)(+) concentrations increased with the percent wetland/saturated area in the catchment but the same trend did not hold for storm-event concentrations. PMID- 17286172 TI - Water level management and contaminant exposure to tree swallows nesting on the Upper Mississippi River. AB - The U.S. Army Corps of Engineers conducted a water drawdown on Navigation Pool 8 of the Upper Mississippi River during the summers of 2001 and 2002 to increase aquatic vegetation production and thereby improve fish and wildlife habitat. Flooding of previously dried wetlands, however, may increase the rate of mercury methylation and make mercury more available to terrestrial vertebrates that feed in aquatic environments. Our objective was to determine if mercury, other elements, and organochlorine contaminants were more available to vertebrates following the 2001 drawdown. Tree swallow (Tachycineta bicolor) eggs and nestlings were collected at two sites on Pool 8 and a nearby Reference site in 2000 (pre-2001 drawdown), 2001 (pre-2001 drawdown) and 2002 (post-2001 drawdown) and tissues were analyzed for mercury, other elements, and organochlorine contaminants. Bioindicator measurements of genetic damage, oxidative stress, ethoxyresorufin-O-dealkylase activity, and the ratio of liver to nestling mass were also measured in nestlings at all sites and all years. Based on a multivariate analysis, the 2001 drawdown of Pool 8 did not influence element concentrations, organochlorine concentrations, or bioindicator response. Concentrations of inorganic and organochlorine contaminants in tree swallow eggs and nestlings were not at toxic levels. Hatching success did not differ among years and was comparable to the nationwide average. PMID- 17286173 TI - Air quality at a snowmobile staging area and snow chemistry on and off trail in a Rocky Mountain subalpine forest, Snowy Range, Wyoming. AB - A study was begun in the winter of 2000-2001 and continued through the winter of 2001-2002 to examine air quality at the Green Rock snowmobile staging area at 2,985 m elevation in the Snowy Range of Wyoming. The study was designed to evaluate the effects of winter recreation snowmobile activity on air quality at this high elevation site by measuring levels of nitrogen oxides (NO( x ), NO), carbon monoxide (CO), ozone (O(3)) and particulate matter (PM(10) mass). Snowmobile numbers were higher weekends than weekdays, but numbers were difficult to quantify with an infrared sensor. Nitrogen oxides and carbon monoxide were significantly higher weekends than weekdays. Ozone and particulate matter were not significantly different during the weekend compared to weekdays. Air quality data during the summer was also compared to the winter data. Carbon monoxide levels at the site were significantly higher during the winter than during the summer. Nitrogen oxides and particulates were significantly higher during the summer compared to winter. Nevertheless, air pollutants were well dispersed and diluted by strong winds common at the site, and it appears that snowmobile emissions did not have a significant impact on air quality at this high elevation ecosystem. Pollutant concentrations were generally low both winter and summer. In a separate study, water chemistry and snow density were measured from snow samples collected on and adjacent to a snowmobile trail. Snow on the trail was significantly denser and significantly more acidic with significantly higher concentrations of sodium, ammonium, calcium, magnesium, fluoride, and sulfate than in snow off the trail. Snowmobile activity had no effect on nitrate levels in snow. PMID- 17286175 TI - Agro-economic evaluation of water resource project--a modeling approach. AB - Feasibility of an irrigation project is evaluated by two criteria viz., reservoir capacity to irrigate its command area and economic returns by incremental crop production versus capital investment for dam construction. The annual water requirement of different crops in the command area is estimated and compared with the availability of water from the dam for irrigation purpose. The annual crop water requirement is estimated as the sum of evapotranspiration for crops and transmission and other losses. Evapotranspiration is estimated by modified Penman formula. Economics of crop production is analyzed by first estimating the monetary value of existing crop production under current rain fed conditions and then estimating the incremental production of irrigated command area for the proposed crop pattern. The proposed cropping pattern is prepared so as to maximize the benefit of crop production and fodder requirement while maintaining a better crop rotation to improve and maintain physical, chemical, and biological conditions of the soil. The dam is to be used for irrigation and water supply only. Command area served by this reservoir will be 76,500 ha. The existing annual agricultural return is Rs. 2995.56 lakhs and with the proposed irrigation scheme, it is estimated as Rs. 1,77,91.90 lakhs. The incremental annual return would be Rs. 1,47,96.35 lakhs i.e., 642.68% increase in annual return. PMID- 17286176 TI - Plant uptake/bioavailability of heavy metals from the contaminated soil after treatment with humus soil and hydroxyapatite. AB - Uptake /bioavailability study using the Indian mustard plant (Brassica juncea) was undertaken at the interval of 7, 14 and 21 days to test the immobilization of heavy metals from contaminated soil that were amended with humus soil and/or hydroxyapatite. For this, four sets consisting of non-humus soil + metals (Cd, Cr, Ni and Pb), humus soil + metals, non-humus and humus soil in the ratio of 1:3 + metals and non-humus soil: humus soil in the ratio of 1:3 + metals + 1% hydroxyapatite were prepared. The bioavailability of Pb, Cd, Cr and Ni in non humus soil system was 58%, 67%, 65% and 63%, respectively in 7 days, more than 80% in 14 days and more than 90% in 21 days. Use of non-humus, humus soil in the ratio of 1:3 and addition of 1% hydroxyapatite decreased the bioavailability of lead around 21 to 22.5%, Cd 35 to 36%, Cr 25.5 to 26.9%, Ni 34 to 39% in 7, 14 and 21 days. Apart from this increase in the fresh weight of the plant was also noticed during the experiment. The data showed that addition of 1% hydroxyapatite in the non-humus-humus soil system caused the increase in the fresh weight around 90% in 7, 14 and 21 days as compared to plant grown in non-humus and metal soil system. PMID- 17286177 TI - Indoor air quality of public places in Mumbai, India in terms of volatile organic compounds. AB - Indoor air quality at nine locations viz. food courts, restaurant, bar, conference room, office and theater, which can be classified as public places have been monitored for Volatile Organic Compounds (VOCs) content. Forty VOCs have been identified and one fourth of these are classified as Hazardous Air Pollutants. Levels of most VOCs are observed to be below the guideline values for public places and offices, as adopted by Hong Kong. Consumer goods are found to be predominant source of chlorinated VOCs in indoor air. Levels of benzene and carbon tetrachlorides were observed to be above the guideline values at all the locations. Effect of ozonisation on Total VOC concentrations have also been studied. PMID- 17286178 TI - Assessing spatial occurrence of ground level ozone around coal mining areas of Chandrapur District, Maharashtra, India. AB - Stratospheric input and photochemical ozone formation in the troposphere are the two main sources determining the ozone levels in the surface layer of the atmosphere. Because of the importance of ozone in controlling the atmospheric chemistry and its decisive role in the heat balance of atmosphere, leading to climate change, the examination of its formation and destruction are of great interest. This study characterized the distribution of Ground level Ozone (GLO) in Chandrapur district is lying between 19 degrees 25'N to 20 degrees 45'N and 78 degrees 50'E to 80 degrees 10'E. Continuous ozone analyzer was used to quantify GLO at thirteen locations fixed by Global Positioning System (GPS) during the winter of 2005-2006. The daily GLO at all the locations ranged between 6.4 and 24.8 ppbv with an average and standard deviation of 14.9 +/- 6.5 ppbv. The maximum and minimum concentration occurs during 1300-1600 h and 0300-0500 h may be due to high solar radiation facilitating photochemical production of O(3) and downward mixing from the overlying air mass and in situ destruction of ozone by deposition and/or the reaction between O(3) and NO. GIS based spatial distribution of GLO in Chandrapur district is indicates that the central core of the district and southern sites experienced elevated levels of GLO relative to the northern and western areas. The sites near by Chandrapur city are particularly affected by elevated GLO. The average variation of GLO with temperature shows a significant correlation of r = 0.55 indicating a direct relationship between GLO and temperature. Similarly an attempt has been made to compare the GLO monitored data in Chandrapur district with the reported values for other locations in Indian cities. This generated database helps regulatory agencies to identify locations where the natural resources and human health could be at risk. PMID- 17286179 TI - Chemical elements and their source apportionment of PM(10) in Beijing urban atmosphere. AB - Monitoring of Beijing PM(10) was undertaken, data collected in a period of one year showed seasonal variation of the mass level of Beijing PM(10) being highest in winter and spring, lower in summer and lowest in autumn. PIXE was used to investigate the chemical elements in PM(10). Results showed the chemical concentration also varied seasonally. Percentage of the masses of the crustal elements such as Al, Si, Mg, K, Ca, Fe, Mn and Ti, reached highest in spring and S, Cl, Pb, As, Cu, Ni and Zn which originated from anthropogenic sources reached highest in winter. The monitoring data showed gradual increase of the abundance of the elements from spring to winter in Beijing air and especially strong correlation of Si, Ca, Al, Fe, Mg and Ti from the factor analysis indicating these elements coming from the earth crust or soil, S, Zn and Pb probably from industrial pollution and Cl and As from combustion. PMID- 17286180 TI - Spectroscopic distribution of dissolved organic matter in a dam reservoir impacted by turbid storm runoff. AB - Spectroscopic characteristics of dissolved organic matter (DOM) in a large dam reservoir were determined using ultraviolet absorbance and fluorescence spectroscopy to investigate spatial distribution of DOM composition after turbid storm runoff. Water samples were collected along a longitudinal axis of the reservoir at three to four depths after a severe storm runoff. Vertical profiles of turbidity data showed that a turbid water layer was located at a middle depth of the entire reservoir. The spectroscopic characteristics of DOM samples in the turbid water layer were similar to those of terrestrial DOM, as demonstrated by the higher specific UV absorbance (SUVA) and the lower fluorescence emission intensity ratio (F(450)/F(500)) compared to other surrounding DOM samples in the reservoir. Synchronous fluorescence spectroscopy revealed that higher content of humic-like DOM composition was contained in the turbid water. Fluorescence excitation-emission matrix (EEM) showed that lower content of protein-like aromatic amino acids was present in the turbid water DOM. The highest protein like fluorescence was typically observed at a bottom layer of each sampling location. The bottom water DOM exhibited extremely high protein-like florescence near the dam site. The particular observation was attributed to the low water temperature and the isolation of the local bottom water due to the upper location of the withdrawal outlet near the dam. Our results suggest that the distribution of DOM composition in a dam reservoir is strongly influenced by the outflow operation, such as selective withdrawal, as well as terrestrial-origin DOM inputs from storm runoff. PMID- 17286181 TI - Faecal coliforms in bivalve harvesting areas of the Alvor lagoon (southern Portugal): influence of seasonal variability and urban development. AB - Faecal coliform (FC) levels in surface water and clams (Ruditapes decussatus) and variations in environmental parameters were studied in two bivalve harvesting areas in the Alvor lagoon (southern Portugal). Land use and cover characteristics in adjacent subwatersheds were also analysed to assess their contributions as sources of faecal contamination. High FC levels in clams from the harvesting area in the most urbanized subwatershed (impervious surface coverage approximately 10.5%) were positively associated with rainfall and with the cooler periods of the year. FC levels in clams from the least urbanized subwatershed were generally very low and did not present any detectable seasonal trend. From these results, it was concluded that the periodic deterioration of the microbiological quality of clams derives from the cumulative impact of the reservoir of faecal contamination created in urbanized areas, entering into the lagoon during storm water runoff. PMID- 17286182 TI - Feasibility of on-line measurement of sewage components using the UV absorbance and the neural network. AB - The objective of this study was to test the feasibility of a new method to improve the accuracy in the estimation of sewage components. Adding to the regression of sewage components with UV (ultraviolet) absorbance values, a proposed method considered an unclear but existing relationship among characteristic of sewage production. Sewage production showed very defined profiles due to the daily human activities. So the main idea was the combination of measuring the UV absorbance values and analyzing the characteristics of the sewage production. For this purpose, 446 sewage samples taken at every 2-h interval for 51 days at a wastewater treatment plant were statistically analyzed using neural network (NN). NN was trained with 350 data sets (about 29 days) of UV absorbance values, flow rate and time. And as a result, it could predict 96 data (12 days) as a validation, indicating that estimation accuracies were improved to higher level than those of the linear regressions. The proposed method could estimate concentrations of total nitrogen (TN) and total phosphate (TP) within practical accuracies as well as total suspended solid. PMID- 17286183 TI - Total mercury distribution in different tissues of frigate tuna (Auxis thazard thazard) from the Atlantic Coastal Waters of Ghana, Gulf of Guinea. AB - Total mercury concentrations in different tissues of frigate tuna fish (Auxis thazard thazard) was determined by the cold vapour atomic absorption spectrometry technique using an automatic mercury analyzer. A mixture of HNO3, HClO4 and H(2)SO(4) was used for complete oxidation of organic tissue. The concentration of mercury obtained was in the order Gills < Stomach < Gonads < Intestine < Heart < Duodenum < Liver < Muscle. The concentration of total mercury detected in the edible muscle tissue of the tuna fish tested ranged from 0.044 to 0.201 microg g( 1) (mean = 0.108 microg g(-1)) wet weight. These levels are all within the maximum allowed/recommended level in fish (0.5 mug g(-1) wet weight) set by the Food and Agriculture Organisation/World Health Organisation (FAO/WHO) and are therefore unlikely to constitute any significant mercury exposure to the general population because of consumption of tuna fish. The results of the study suggest a relatively clean marine environment that has not been significantly impacted by mercury contamination probably due to minimal industrial activity in the region. PMID- 17286184 TI - Environmental impact assessment of industrial structure change in a rural region of China. AB - As the embodiment of human activities, the change of regional industrial structure is an essential driving factor of global environmental change. Consequently, the research on the change of regional industrial structure and associated effects on the environment is one of the key issues of researches on sustainable development, human-environment relationship, and regional response to global environment change. However, compared to the flourish of researches on environmental impact assessment of industrial departments, few studies have been conducted to assess the environmental impact of regional industrial structure. In this study, based on a synthetic analysis of environmental disturbances of different industrial departments, the environmental impact coefficient of industrial department associated with the index of environmental impact of industrial structure was constructed, so as to make a quantitative assessment of environmental impact of the change of regional industrial structure. And the results of the case study in Lijiang City, a rural region of China, have showed that there are two obvious changes of industrial structure in the study area from 1992 to 2003, associated with a continuous decreasing of the index of environmental impact of industrial structure, which indicated a positive environmental effects of the change of regional industrial structure. PMID- 17286185 TI - Rapid regression of extensive retinovitreal neovascularization secondary to branch retinal vein occlusion after a single intravitreal injection of bevacizumab. AB - PURPOSE: To report the rapid regression of extensive retinovitreal neovascularization following the administration of a single dose of intravitreal bevacizumab. METHODS: A 60-year-old woman presented with recurrent vitreous hemorrhage originating from active retinovitreal neovascularization secondary to branch retinal vein occlusion. The neovascular tissue remained active despite multiple sessions of laser therapy. Intravitreal injection of 1.25 mg bevacizumab was performed. RESULTS: Rapid regression of the retinovitreal neovascularization, a marked reduction in retinal vein engorgement, and visual improvement was observed 1 week after the intervention CONCLUSION: Intravitreal bevacizumab can result in the rapid and dramatic regression of retinovitreal neovascularization refractory to previous laser photocoagulation. PMID- 17286186 TI - Traumatic tear of the inferior rectus muscle treated with inferior oblique anterior transposition. AB - PURPOSE: To report a case of traumatic tear of the inferior rectus muscle treated with inferior oblique anterior transposition (IOAT). METHODS: Case report of a 55 year-old man who presented with vertical diplopia (VD) after orbital trauma. Ocular examination disclosed a 62PD right hypertropia (RHT) in the primary position (PPO). The right inferior rectus (RIR) was torn, and the distal stump was fixed to the skin with tape. RESULTS: Surgery was performed under local anesthesia. The RIR tearing occurred 13 mm from the insertion, and exploration revealed its proximal end. The right inferior oblique (RIO) was intact, although its fibers were loose. Since the RHT did not improve following reattachment of the proximal and distal stumps of the RIR, the distal stump was excised and the proximal end brought forward and sutured 6.5 mm from the limbus. At perioperative evaluation, there was a 25PD RHT in PPO where the VD persisted. The RIO was subsequently isolated, detached, and its distal end, after 6 mm resection, was sutured to a point temporal to the lateral border of the RIR. The patient was reevaluated and had neither RHT nor VD in primary gaze. At the 6-week postoperative evaluation, he was orthotropic in PPO, complaining about diplopia only on extreme downgaze. A mild limitation of right depression was observed. The patient was satisfied with the surgical results and experienced no functional limitations during any activities. CONCLUSION: IOAT can provide acceptable binocular visual function without the risk of anterior segment ischemia in cases of torn inferior rectus muscle. PMID- 17286187 TI - Genetic insight into Mediterranean chukar (Alectoris chukar, Galliformes) populations inferred from mitochondrial DNA and RAPD markers. AB - The chukar (Alectoris chukar, Galliformes) is one of the most important game birds as it is widely distributed and hunted over the whole of its range. The aim of this work was to assess the genetic differentiation as well as the possible presence of hybrid specimens in A. chukar populations from Italy, Greece and Cyprus. To provide phylogenetic context, conspecific, allopatric specimens from Israel, Georgia, Armenia, Kazakhstan, Afghanistan, Pakistan, Mongolia, China and USA were compared. Sequencing of the mitochondrial DNA (mtDNA) Control Region supplied information on the ancestry of A. chukar populations, whereas Random Amplified Polymorphic DNA (RAPD) fingerprinting was used to assess whether hybridization had occurred. The Italian population was found to be an inter specific mixture of A. chukar and A. rufa (i.e., the red-legged partridge) mtDNA lineages, whereas the representatives from Greece and Cyprus showed only the A. chukar maternal line. RAPD markers revealed introgression with A. rufa genes in the Italian population, whereas no A. chukar x A. rufa hybrid specimens were detected in the eastern Mediterranean populations. The genetic data obtained from the Italian A. chukar population as well as from a few Greek specimens pointed against their Mediterranean kinship, suggesting relationships with A. chukar subspecies from the easternmost part of the Asian continent. PMID- 17286188 TI - Alterations in Rubisco activity and in stomatal behavior induce a daily rhythm in photosynthesis of aerial leaves in the amphibious-plant Nuphar lutea. AB - Nuphar lutea is an amphibious plant with submerged and aerial foliage, which raises the question how do both leaf types perform photosynthetically in two different environments. We found that the aerial leaves function like terrestrial sun-leaves in that their photosynthetic capability was high and saturated under high irradiance (ca. 1,500 mumol photons m(-2) s(-1)). We show that stomatal opening and Rubisco activity in these leaves co-limited photosynthesis at saturating irradiance fluctuating in a daily rhythm. In the morning, sunlight stimulated stomatal opening, Rubisco synthesis, and the neutralization of a night accumulated Rubisco inhibitor. Consequently, the light-saturated quantum efficiency and rate of photosynthesis increased 10-fold by midday. During the afternoon, gradual closure of the stomata and a decrease in Rubisco content reduced the light-saturated photosynthetic rate. However, at limited irradiance, stomatal behavior and Rubisco content had only a marginal effect on the photosynthetic rate, which did not change during the day. In contrast to the aerial leaves, the photosynthesis rate of the submerged leaves, adapted to a shaded environment, was saturated under lower irradiance. The light-saturated quantum efficiency of these leaves was much lower and did not change during the day. Due to their low photosynthetic affinity for CO(2) (35 muM) and inability to utilize other inorganic carbon species, their photosynthetic rate at air equilibrated water was CO(2)-limited. These results reveal differences in the photosynthetic performance of the two types of Nuphar leaves and unravel how photosynthetic daily rhythm in the aerial leaves is controlled. PMID- 17286189 TI - Acclimation of photosystem II to high temperature in a suspension culture of soybean (Glycine max) cells requires proteins that are associated with the thylakoid membrane. AB - In a study of the responses of photosystem II (PSII) to high temperature in suspension-cultured cells of soybean (Glycine max L. Merr.), we found that high temperatures inactivated PSII via two distinct pathways. Inactivation of PSII by moderately high temperatures, such as 41 degrees C, was reversed upon transfer of cells to 25 degrees C. The recovery of PSII required light, but not the synthesis of proteins de novo. By contrast, temperatures higher than 45 degrees C inactivated PSII irreversibly. An increase in the growth temperature from 25 to 35 degrees C resulted in an upward shift of 3 degrees C in the profile of the heat-induced inactivation of PSII, which indicated that the thermal stability of PSII had been enhanced. This acclimative response was reflected by the properties of isolated thylakoid membranes: PSII in thylakoid membranes from cells that had been grown at 35 degrees C exhibited greater thermal stability than that from cells grown at 25 degrees C. Disruption of the vesicular structure of thylakoid membranes with 0.05% Triton X-100 decreased the thermal stability of PSII to a similar level in both types of thylakoid membrane. Proteins released by Triton X 100 from thylakoid membranes from cells grown at 35 degrees C were able to increase the thermal stability of Triton-treated thylakoid membranes. These observations suggest that proteins that are associated with thylakoid membranes might be involved in the enhancement of the thermal stability of PSII. PMID- 17286190 TI - Investigating UV screening in leaves by two different types of portable UV fluorimeter reveals in vivo screening by anthocyanins and carotenoids. AB - Two portable instruments, designed to evaluate epidermal UV screening in leaves, were compared: the Dualex and the UV-A-PAM fluorimeter. Both instruments excite chlorophyll fluorescence at the same UV wavelengths but reference excitation is in the red and the blue spectral range in the former and the latter fluorimeter, respectively. When analyzing green leaves, general agreement of the data is obtained with the two instruments. In the presence of anthocyanins, the UV-A-PAM fluorimeter provided higher estimates for epidermal UV transmittance than the Dualex fluorimeter, which was attributed to absorption of blue excitation light by anthocyanins. By comparing data from the instruments, anthocyanin-dependent transmittance of 50% was determined in abaxial sides of some autumn leaves, and also in abaxial sides of tropical shade plants. Further, with leaves of chlorophyll b-less mutants of H. vulgare, unusually high epidermal UV transmittance was detected but this was attributed to the lack of chlorophyll b absorption and, in addition, to absorption of blue radiation by xanthophylls which are not functionally connected to photosystems. PMID- 17286191 TI - Relation between level or change of hemoglobin and generic and disease-specific quality of life measures in hemodialysis. AB - OBJECTIVE: We sought to examine the relation between meeting or exceeding the current minimum guideline for hemoglobin (11 g/dl) in dialysis patients and generic and disease-specific QOL scores at 1 year. METHODS: In 438 incident hemodialysis patients from a national prospective cohort study, we used regression models to predict QOL score (all scaled 0-100) at 1 year using 6-month values of hemoglobin, adjusting for potential confounders. RESULTS: Compared to values < 11 g/dl, hemoglobin > or = 11 g/dl at 6 months was associated with higher scores for the general domains of physical functioning, role physical, mental health, social functioning, and bodily pain at 1 year; cognitive function, diet restriction, and dialysis access dialysis-specific domain scores were also higher for these patients. Each 1 g/dl greater hemoglobin was also statistically significantly associated with higher QOL scores for most domains. In longitudinal analyses, most of the domains showed that, with each 1 g/dl increase in hemoglobin concentration from baseline to 6 months, QOL score increased significantly over the first year. CONCLUSIONS: Hemodialysis patients who attain higher hemoglobin concentration at 6 months, especially > or = 11 g/dl, have better QOL at 1 year, with regard to important physical, mental, social, and cognitive domains. PMID- 17286192 TI - Effectiveness of a psycho-educational intervention for reducing burden in Latin American families of patients with schizophrenia. AB - OBJECTIVES: To explore the effectiveness of a psycho-educational family intervention program for reducing burden in caregivers of patients with schizophrenia in a developing country. METHOD: Forty-five caregivers participated, 22 in a psycho-educational family intervention group and 23 in a control group. The family program was held once a week for 5 months. In the control group the caregivers received standard intervention, comprising periodical meetings with the staff to monitor the effects of the medication. Burden was measured before and after the intervention: relatives in the psycho educational group were evaluated at inclusion and at the end of the program; controls were evaluated at inclusion and 5 months later. RESULTS: Burden decreased significantly in the psycho-educational group; mean scores on the Zarit Caregiver Burden Scale fell from 85.06 pre-intervention to 52.44 post intervention, while scores fell only slightly in the control group, from 87.65 to 87.22. Treatment was especially effective in mothers and caregivers with lower educational levels. CONCLUSION: This intervention program for reducing caregiver burden in developing Latin American countries was effective. Future investigations should focus on obtaining more precise estimates of the contributions of specific components of these programs to reducing burden. PMID- 17286193 TI - Translation, cultural adaptation, cross-validation of the Turkish diabetes quality-of-life (DQOL) measure. AB - OBJECTIVE: The aim of this study was to test the validity and reliability of the Turkish version of the diabetes quality of life (DQOL) questionnaire for use with patients with diabetes. METHODS: Turkish version of the generic quality of life (QoL) scale 15D and DQOL, socio-demographics and clinical parameter characteristics were administered to 150 patients with type 2 diabetes. Study participants were randomly sampled from the Endocrinology and Diabetes Outpatient Department of Dr. Lutfi Kirdar Kartal Education and Research Hospital in Istanbul, Turkey. RESULTS: The Cronbach alpha coefficient of the overall DQOL scale was 0.89; the Cronbach alpha coefficient ranged from 0.80 to 0.94 for subscales. Distress, discomfort and its symptoms, depression, mobility, usual activities, and vitality on the 15 D scale had statistically significant correlations with social/vocational worry and diabetes-related worry on the DQOL scale indicating good convergent validity. Factor analysis identified four subscales: satisfaction", impact", "diabetes-related worry", and "social/vocational worry". CONCLUSION: Statistical analyses showed that the Turkish version of the DQOL is a valid and reliable instrument to measure disease related QoL in patients with diabetes. It is a simple and quick screening tool with about 15 +/- 5.8 min administration time for measuring QoL in this population. PMID- 17286194 TI - Does an informative video before inguinal hernia surgical repair influence postoperative quality of life? Results of a prospective randomized study. AB - PURPOSE: Patients undergoing surgery can be impaired in several health-related quality of life areas. As a result, a modern and effective presentation of medical information before elective surgery is of great importance. Thorough preoperative education of the patient could possibly lead to an improvement of postoperative quality of life. MATERIALS AND METHODS: In a prospective randomized study we examined the influence of a preoperative informative video on the postoperative quality of life of patients undergoing elective surgery for inguinal hernia. Quality of life was assessed with a short form questionnaire (SF 36) preoperatively, on the first postoperative day and 3, 6, and 12 months after surgery. RESULTS: From January 2004 until January 2005, 100 patients were included in the study (video group n = 50 patients, control group n = 50 patients). Quality of life was measured higher in the video group soon after surgery and until 3 months afterwards. In the same group other aspects evaluated such as "global health" and "social role" showed higher values postoperatively and resumption of preoperative activities took place earlier. No difference was detectable 6 months after surgery. CONCLUSION: Informative video presents a modern and cost-effective method for the justified and detailed education of the patient about the several pre-, intra-, and postoperative steps of an elective groin hernia operation. The higher information level and the better conditions of surgical care, as the patients perceive these, lead to a better postoperative quality of life. PMID- 17286196 TI - The OVIS study: health related quality of life measured by the EORTC QLQ-C30 and BR23 in German female patients with breast cancer from Schleswig-Holstein. AB - The OVIS study is a population-based study that aims at evaluating medical care in Schleswig-Holstein (Germany). In this paper, the health related quality of life (QoL, EORTC QLQ-C30 and -BR23) of 1,927 women with breast cancer is reported. The global health status/QoL score was comparable to reference data of the age-adjusted German general population, but clinical meaningful differences (> or = 10 points) were found for all functioning scales (with the exception of physical functioning) and for three of the symptom scales/items (fatigue, dyspnoe, insomnia) with OVIS patients showing more deficits. Furthermore, OVIS patients scored higher on the item financial difficulties. Logistic regression analyses revealed that coming from an urban surrounding, having a higher social status and attendance to a regular aftercare predicted a good overall QoL, while factors that were related to perceived complications in the course of the therapy raised the risk for a low QoL rating. It is of interest, that attendance to a rehabilitation and interest in self-help groups independently predicted an increased risk for a low quality of life. Overall, we assume the global QoL is rating slightly too optimistic since major deficits were reported on the specific physical and functional scales/items. PMID- 17286195 TI - The relationship between gender, social support, and health-related quality of life in a community-based study in Washington County, Maryland. AB - OBJECTIVE: Men tend to report higher health-related quality of life (HRQOL) than women of the same age, despite higher mortality rates and lower life expectancy. Social support is one factor related to HRQOL that may contribute to the observed gender difference. The purpose of this study was to determine the factors associated with HRQOL, especially levels of social support, and variation by gender. METHODS: Multivariable logistic regression was used to analyze data from 4,498 men and 6,948 women participating in an ongoing community-based cohort study in Washington County, Maryland (CLUE-II). RESULTS: The results showed that men reported significantly better HRQOL than women. Men reported having higher levels of social support than women, but the magnitude of the association with HRQOL was similar. Having two or less close friends was associated with a statistically significant increase in the odds of reporting poorer HRQOL compared to having 10 or more close friends among both genders (men: OR = 1.49; women: OR = 1.53). Differences in the level of social support did not explain the gender difference in HRQOL. CONCLUSIONS: Our findings show that social support is an important correlate of HRQOL for both men and women. However, the gender differences in HRQOL are not explained by social support or the other factors examined. PMID- 17286197 TI - Feasibility, reliability, and validity of adolescent health status measurement by the Child Health Questionnaire Child Form (CHQ-CF): internet administration compared with the standard paper version. AB - AIMS: In this study we evaluated indicators of the feasibility, reliability, and validity of the Child Health Questionnaire-Child Form (CHQ-CF). We compared the results in a subgroup of adolescents who completed the standard paper version of the CHQ-CF with the results in another subgroup of adolescents who completed an internet version, i.e., an online, web-based CHQ-CF questionnaire. METHODS: Under supervision at school, 1,071 adolescents were randomized to complete the CHQ-CF and items on chronic conditions by a paper questionnaire or by an internet administered questionnaire. RESULTS: The participation rate was 87%; age range 13 17 years. The internet administration resulted in fewer missing answers. All but one multi-item scale showed internal consistency reliability (Cronbach's alpha > 0.70). All scales clearly discriminated between adolescents with no, a few, or many self-reported chronic conditions. The paper administration resulted in statistically significant, higher scores on 4 of 10 CHQ-CF scales compared with the internet administration (P < 0.05), but Cohen's effect sizes d were 97th centile; mean age 13.8+/-4.1 yr) and 109 parents (79 mothers/30 fathers) of 88 of these patients were studied. The MC4R coding region was screened using denaturing high-performance liquid chromatography (dHPLC); PCR products of aberrant dHPLC pattern were re-sequenced. Signal transduction properties of mutant MC4R was investigated by challenge with the highly potent agonist NDP-alpha-MSH. Cell surface expression was determined by ELISA. Magnetic resonance imaging (MRI) of the central nervous system (CNS) was applied to a 2.3 year old index patient. Body fat and bone mineral content were assessed in three of the five mutation carriers by dual energy x-ray absorptiometry (DEXA). Oral glucose tolerance test (OGTT) was applied to some mutation carriers. RESULTS: Heterozygous carriers of two non-synonymous mutations, two polymorphisms and a silent variation were identified within the study group. (1) A novel MC4R non synonymous mutation (S136F) was detected in a 2.3 year old girl with extreme obesity (BMI 33.2 kg/m(2), >99th centile); (2) a previously described non synonymous mutation (V253I) was identified in an obese mother (BMI 28.1 kg/m(2)) who did not transmit this mutation to her extremely obese son; (3) two known polymorphisms (V103I and I251L) were also identified; and (4) one obese mother was carrier of a silent variation (c.594C>T; I198). Co-segregation of S136F with the obesity phenotype was shown for three generations. IN VITRO functional studies revealed a complete loss of signal transduction activity of the mutant receptor while cell surface expression was only slightly reduced compared to the wild-type receptor. CONCLUSIONS: We detected a novel non-synonymous mutation (S136F) that leads to a complete loss of MC4R function IN VITRO. PMID- 17286228 TI - Ectopic Cushing's syndrome due to concurrent corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) secreted by malignant gastrinoma. AB - Ectopic Cushing's syndrome due to various malignancies is not uncommon. However, a few cases of ectopic Cushing's syndrome caused by corticotropin-releasing hormone (CRH), or CRH with adrenocorticotropic hormone (ACTH) have been reported. A 28-year-old woman presented with acute upper gastrointestinal bleeding caused by an active ulcer, located atypically in the 2nd portion of duodenum. Further work-up revealed high gastrin levels and abdominal computed tomography (CT) scans showed a large pancreatic head mass with multiple liver metastases. The serum cortisol and ACTH levels were checked due to hypokalemia with metabolic alkalosis and recent amenorrhea. Cortisol and ACTH were both highly elevated with pituitary hyperplasia and elevated CRH. The existence of ectopic ACTH and CRH in the liver biopsy was also demonstrated immunohistochemically. Since an operation was not feasible, chemotherapy was conducted using paclitaxel and etoposide. These two drugs were chosen according to the IN VITRO chemotherapy response assay to maximize the treatment. This report demonstrates concurrent ACTH- and CRH-related ectopic Cushing's syndrome caused by malignant gastrinoma with multiple liver metastases that was treated with marginal success using a multidisciplinary medical approach. PMID- 17286229 TI - Modulation of circulating IGF-I and IGFBP-3 levels by hormonal regulators of energy homeostasis in obese children. AB - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are key factors in the control of somatic growth. Recent work revealed a critical role for the transcription factor STAT5b in GH stimulated IGF-I gene expression. In obesity, the normal regulation of the GH/IGF-I axis is disturbed, with normal levels of circulating IGF-I despite blunted GH secretion. We hypothesized that leptin or other hormonal regulators of energy homeostasis, which can activate Stat5b regulated gene expression or exert an effect on GH secretion, might be able to substitute for GH in terms of IGF-I synthesis. Thus, the aim of this study was to identify potential regulators of IGF-I serum levels in obesity with a particular focus on the interaction of leptin and IGF-I. In a cross-sectional study, we measured hormonal and auxiological parameters in 99 obese children who were referred to our obesity outpatient clinic and analysed correlations between unadjusted hormone levels and between hormone concentrations expressed as SDS values, adjusted for sex, age, and/or puberty and BMI. Serum concentrations of IGF-I correlated highly significant with IGFBP-3, leptin, fasting ghrelin and insulin (p<0.001). However, when expressing hormone levels as SDS values, only leptin SDS and IGFBP-3 SDS correlated significantly with IGF-I SDS (p<0.01). This correlation between leptin SDS and IGF-I SDS was more pronounced in prepubertal and in male subjects, with increasing IGF-I SDS values paralleling an increase in leptin SDS tertiles in prepubertal subjects. In linear regression analyses, leptin SDS, IGFBP-3 SDS and BMI SDS contributed significantly to the variation of IGF-I SDS values, and explained 53.3% of the variability of IGF-I SDS levels in male subjects. SUMMARY AND CONCLUSIONS: In summary, we demonstrated a strong correlation of age and sex-adjusted standard deviation scores (SDS) for IGF-I and leptin in obese children, which is modulated by sex, pubertal stage and body weight. Whether this association results from a direct induction of hepatic IGF-I gene expression by leptin or reflects a more complex interrelationship between IGF-I and obesity-related factors should be subject of future research. PMID- 17286230 TI - Establishment of a cell-based drug screening model for identifying down regulators of Protein Tyrosine Phosphatase 1B expression. AB - Protein Tyrosine Phosphatase 1B (PTP1B), an important negative regulator of insulin signaling, is thought to be an attractive therapeutic target for insulin resistance and type 2 diabetes. For the aim of screening PTP1B expression down regulators, we established the drug screening cellular model based on transcriptional regulation of PTP1B. In this study, the promoter sequences of PTP1B were cloned into pGL3B-neo vector containing luciferase gene and neomycin resistance gene. The recombinant reporter gene vector pGL3B-neo /PTP1B was transfected into CV1 cells and therefore stable cell line, namely SPTP1B, was obtained. With the cell-based reporter gene assay, we detected more than one hundred compounds in microtiter wells. In the screening process, the compound CM107 which had extracted from the traditional Chinese medicinal herbs was identified to repress the activity of PTP1B promoter significantly in mode of dose-dependence. PMID- 17286231 TI - Effect of creatine on the pancreatic beta-cell. AB - We report on the stimulatory effect of creatine on insulin secretion and ATP concentration in MIN-6 beta-cells. The addition of creatine (5 mM) to MIN-6 cells in the presence of glucose (1-10 mM) elicited a significant (p<0.001) increase in insulin secretion, but no effect was demonstrated in the absence of glucose. The lack of effect of creatine in the absence of glucose suggests that creatine may act as a potentiator of insulin secretion rather than as an initiator. The potentiatory effect of creatine is specific for glucose since no effect was found in the presence of other known initiators of insulin secretion (K(+), 2 ketoisocaproic acid and tolbutamide). Cellular ATP content was markedly increased by glucose (1-15 mM). Creatine (5 and 10 mM) further increased the ATP level at all glucose concentrations, and the effect was observed even in the absence of glucose. The results from this study demonstrate the ability of creatine to increase insulin secretion only in the presence of glucose, while its effect on increased cellular ATP was independent of the presence of glucose. The mechanism whereby creatine potentiates insulin release is yet to be investigated. However, our data suggest possible unique interactions between creatine and the glucose dependent insulin secretory pathway. PMID- 17286232 TI - Shorter remission period in young versus older children with diabetes mellitus type 1. AB - BACKGROUND: The initial period of diabetes type 1 is of great importance, since early metabolic adjustment has profound impact on long term control. The majority of pediatric centers in Germany participate in a national quality initiative, providing longitudinal data for central analysis. PATIENTS: 104543 anonymous data sets were obtained from 6123 pediatric patients under 18 years who were treated in 157 pediatric centers and monitored for 36 months at the same center starting from diagnosis. RESULTS: Partial remission (insulin <0.5 U/kg/d and HbA1c < or = 7.0%) was present in 1992 children (32.5%) within the first 3 months after diagnosis. Remission phase lasted in average for 0.74 +/- 0.77 years and was significantly shorter in children below 10 years of age at onset of diabetes compared to the older patients. The remission period was significantly longer in boys, particularly in children under 10 years (p=0.0039). Multiple regression analysis showed a longer remission phase in children with pubertal diabetes onset. The children entering remission were younger, more often boys and had a lower initial HbA1c level. CONCLUSION: These data from a large multicenter group of children with diabetes type 1 emphasize the influence of gender, pubertal stage and age at manifestation on the amount of insulin required, and therefore the clinical remission, during the first three years of the disease. PMID- 17286233 TI - Association of low-grade inflammation with nephropathy in type 2 diabetic patients: role of elevated CRP-levels and 2 different gene-polymorphisms of proinflammatory cytokines. AB - BACKGROUND: Chronic inflammatory processes are thought to play a key role in the development of micro- and macrovascular complications in type 2 diabetes mellitus. An association between low -grade inflammation and type 2 diabetes has been described in some studies. We assayed the association of two frequent polymorphisms in proinflammatory cytokines: the interleukin 6 G(-174)C promoter polymorphism [IL-6G(-174)C], the exon 2 interleukin receptor antagonist insertion deletion polymorphism [IL1RA]) and serum CRP levels with the prevalence of diabetic nephropathy in patients suffering from type 2 diabetes mellitus. SUBJECTS AND METHODS: A total of 141 patients with type 2 diabetes mellitus, with and without diabetic nephropathy was genotyped for the above mentioned polymorphisms: 66 with normoalbuminuria, 31 with microalbuminuria and 44 with macroalbuminuria. CRP levels were analysed by a high sensitivity - immunnephelometric assay. RESULTS: While a significant association be-tween macroalbuminuria and CRP could be observed (p<0,015), no associations were found between IL-6G(-174)C or IL1RA genotype and any stage of nephropathy. CRP-levels were similar in the 3 different IL-6G(-174)C genotypes as well as in the 2 IL1RA genotypes. CONCLUSIONS: In type 2 diabetic subjects elevated CRP levels are associated with an increased prevalence of albuminuria. The two investigated proinflammatory polymorphisms do not seem to contribute to initiation of nephropathy in type 2 diabetic patients but we cannot exclude effects of these polymorphisms on course of nephropathy. PMID- 17286234 TI - Mood and cognitive functions during acute euglycaemia and mild hyperglycaemia in type 2 diabetic patients. AB - INTRODUCTION: Hyperglycaemia at levels above 15 mmol/l has been shown to impair cognitive functions in type 2 diabetic patients, while effects of mild hyperglycaemia and acute euglycaemia on mood and cognition have rarely been compared. We examined mood and cognitive functions in patients with T2DM during acute euglycaemia in comparison with moderate hyperglycaemia. METHODS: One euglycaemic (5 mmol/l) and one hyperglycaemic clamp (10.5 mmol/l) of 90 min each were performed in 15 T2DM patients in a balanced, single-blind, within-subject comparison. Mood, cognitive functions (assessed via short-term memory and attention tests) and symptoms related to glycaemic changes were assessed during a baseline period and during both glycaemic plateaus. In addition, patients estimated their blood glucose level and counterregulatory hormones were measured. RESULTS: None of the assessed aspects of cognitive functions differed between conditions (all p > or = 0.2). Patients rated higher on the well-being scale (p=0.04) and tended to feel less anger (p=0.08) during hyperglycaemia. Self estimated blood glucose levels were higher during the hyper- than euglycaemic condition (8.6 +/- 2.5 vs 7.2 +/- 1.2 mmol/l; p<0.05) although most individual estimations did not match the actual glucose levels. Counterregulatory hormone levels did not differ (all p>0.25). CONCLUSIONS: Data indicate that T2DM patients are not cognitively impaired by moderate hyperglycaemia (10.5 mmol/l), pointing to the possibility of a glycaemic threshold for cognitive impairments at higher glycaemic levels. PMID- 17286235 TI - 99mTc-EDDA/HYNIC-octreotate in detection of atypical bronchial carcinoid. AB - Pulmonary carcinoids cause serious difficulties in imaging diagnostics in all stages of the disease. SRS holds great promise for detecting occult primary tu and metastatic lesions. (99m)Tc-EDDA/HYNIC-octreotate, a new scintigraphic agent, should significantly improve sensitivity of the diagnostics of carcinoids due to better affinity to SSR2 than (111)In-Octreoscan and the higher count rate obtained from (99m)Tc over (111)In. We present a case of a 40-year-old women operated on because of lung carcinoid tumour in 2002. The symptoms did not resolve after the operation and 5-OHIAA was still elevated. The thorax spiral CT revealed the focal lesion beneath carina. (111)In-Octreoscan and (99m)Tc EDDA/HYNIC-octreotate SRS revealed two focal lesions in the mediastinum. (99m)Tc EDDA/HYNIC-octreotate detected two additional lesions in the lower part of the right lung. Target/non-target count ratios of the lesions were as follows: (99m)Tc-EDDA/HYNIC-octreotate scans - 2,9, (111)In-Octreoscan- 2,1. PET-FDG examination revealed no pathology. Owing to severe bone pains and carcinoid symptoms the patient was referred for the 90Y-DOTA-octreotate treatment. CONCLUSIONS: SRS with a new 99mTc marked somatostatin analogue - octreotate allows for a more sensitive detection of metastatic leasions in carcinoid tumours. The usefulness of 18F-FDG PET, widely used as a powerful imaging technique in clinical oncology, is limited in detection of carcinoid tumours due to the low proliferative activity. PMID- 17286236 TI - Sporadic hypoparathyroidism treated with teriparatide: a case report and literature review. AB - Herein we describe the case of a 64-year-old woman with hypoparathyroidism diagnosed at the age of 40, after an acute episode of tetany and seizures due to severe hypocalcemia. She was treated for more than 20 years with calcitriol and calcium supplementation but she presented with marked hypercalciuria and recently nephrolithiasis, although serum calcium was maintained at levels below normal range. Provided that any attempt to increase the recommended dose of calcitriol was leading to an exacerbation of hypercalciuria, we decided to enroll an alternative tool in the treatment strategy. In order to avoid further deterioration of renal function she was administered once-daily a subcutaneous (sc) injection of synthetic human parathyroid hormone (PTH 1-34) while doses of calcium and calcitriol were gradually decreased depending on the response of calcium metabolism in serum and urine samples taken periodically. Within two months of administration, PTH (1-34) significantly reduced the level of urine calcium excretion compared with calcitriol therapy and maintained serum calcium in the normal range. The relevant literature is reviewed in light of this alternative therapeutic approach in long-standing hypoparathyroidism, illustrating the potential benefits and the unresolved issues in parathyroid hormone replacement. PMID- 17286237 TI - Charcot's joint of the wrist in type 2 diabetes mellitus. AB - In patients with diabetes mellitus, Charcot's neuroarthropathy mainly affects major weight-bearing joints, especially the foot and ankle. Remarkably, we report a case of Charcot's joint of the wrist - an unusually rare localization in type 2 diabetic patient. A review of medical literature identified only three such cases so far. PMID- 17286238 TI - Use of the new indicator test (Neuropad) for the assessment of the staged severity of neuropathy in type 2 diabetic patients. AB - The new indicator test for sudomotor function (Neuropad) has been shown to represent a highly sensitive and reproducible tool for the diagnosis of diabetic peripheral neuropathy. This study aimed to examine the utility of the indicator test in the assessment of the staged severity of neuropathy in patients with type 2 diabetes mellitus. The study included 120 type 2 diabetic patients (58 men) with a mean age of 67.3+/-5.9 years and a mean diabetes duration of 13.1+/-3.2 years. Neuropathy was diagnosed and staged by clinical examination and nerve conduction study, according to the Michigan classification system. Patients were also examined with the indicator test, applied on the plantar aspect of the feet. Time until complete colour change of the test was recorded and stratified into deciles according to the spread of measurements in the study population. Neuropathy was staged as class 0 in 37 patients, class 1 in 44 patients, class 2 in 28 patients and class 3 in 11 patients. Time until complete colour change was 436.5+/-62.9, 740+/-88.1, 1192.5+/-161 and 1817.3+/-127.4 seconds in patients staged as class 0, 1, 2 and 3 respectively (p=0.001). Use of a threshold lower than 530 seconds until complete colour change had 97% sensitivity and 100% specificity for diagnosis of class 0 neuropathy. Use of a threshold lower than 1000 seconds until complete colour change had 100% sensitivity and 97% specificity for class 1 neuropathy. A threshold lower than 1440 seconds had 93% sensitivity and 100% specificity for class 2 neuropathy. A threshold above 1440 seconds had 100% sensitivity and 99% specificity for class 3 neuropathy. A highly significant (Kendall's tau-b=0.848, p=0.001) correlation was shown between time until complete colour change of the test and Michigan class of neuropathy. CONCLUSIONS: It appears that the indicator test contributes substantially to the assessment of the staged severity of neuropathy in patients with type 2 diabetes mellitus. There is excellent agreement between the indicator test and the Michigan classification system. These results suggest a role for the indicator test in the assessment of diabetic neuropathy. PMID- 17286239 TI - Two Caucasian families with the hepatocyte nuclear factor-1alpha mutation Tyr218Cys. AB - We report on the first two Caucasian families with the MODY3 HNF-1alpha mutation Tyr218Cys. Clinical and laboratory examinations are shown in detail. Patients with HNF-1alpha related MODY may develop the full spectrum of diabetic complications. Therefore, early detection of family members with MODY3 is warranted. PMID- 17286240 TI - Morinda citrifolia (Noni) fruit--phytochemistry, pharmacology, safety. AB - Products derived from Noni fruit (Morinda citrifolia) have been commercialised in the USA since the 1990s and are increasingly distributed all over the world. A large number of beneficial effects have been claimed for Noni. Fruit juice of Noni has been approved as a Novel Food by the European Commission in 2003. This article reviews current knowledge on the phytochemistry, pharmacology, safety aspects of Noni fruit and Noni-derived products, and health-related claims and benefits. The knowledge on the chemical composition of Noni fruit has considerably increased over recent years. A number of in vitro and, to a certain extent, in vivo studies demonstrate a range of potentially beneficial effects. However, clinical data are essentially lacking. To what extent the findings from experimental pharmacological studies are of potential clinical relevance is not clear at present. Based on a toxicological assessment, Noni juice was considered as safe. Due to recent reports of cases of hepatotoxicity, the safety issue has been re-examined in Europe. While the European Food Safety Authority sees no link between adverse effects on liver and consumption of Noni juice, a continuing monitoring of the situation is desirable and some vigilance advised. PMID- 17286241 TI - In vitro acetylcholinesterase inhibitory activity of the essential oil from Acorus calamus and its main constituents. AB - The in vitro acetylcholinesterase (AChE) inhibitory potential of the hydroalcoholic extract and of the essential oil from Acorus calamus (AC) rhizomes and that of its major constituents were evaluated based on the Ellman's method. GC/MS analysis of the oil revealed that the major constituents were beta-asarone (79.54%) and alpha-asarone (8.47%). The IC50 values were obtained for the hydroalcoholic extract, the essential oil, beta-asarone and alpha-asarone and were 182.31+/-16.78 microg/mL, 10.67+/-0.81 microg/mL, 3.33+/-0.02 microM and 46.38+/-2.69 microM, respectively. Physostigmine was used as standard inhibitor with an IC50 value of 0.28+/-0.015 microM. The experimental observations revealed that the AC essential oil and its constituents have significant AChE inhibitory potential. beta-Asarone, the major phytoconstituent present in the essential oil, showed the maximum inhibitory potential. PMID- 17286242 TI - [Broad-spectrum PCR assay for detection of human papillomaviruses in oropharyngeal cancer]. AB - OBJECTIVE: The multitude of studies yielding varying results concerning analysis of the prevalence of human papillomavirus in squamous cell carcinoma of the head and neck gives emphasis to the different methodologies applied. Typical histological changes i. e. koilocytosis, hyperkeratosis and parakeratosis indicating HPV infection are frequently observed, but detection of the virus often fails. MATERIAL AND METHODS: 61 specimens of oropharyngeal squamous carcinomas were investigated at the time of primary diagnosis as well as after radiation or combined radio-chemotherapy. Aim of the present study was to establish a molecular detection system including a broad spectrum of different HPV-types. This could be achieved by applying so-called degenerated consensus primers. By using voluntarily altered base-pair sequences in a highly conserved region of the HPV genome, the oligonucleotide primers were sensitive to the huge sequence variance of different HPV-types. Furthermore, sensitivity of the primary PCR was enhanced by applying a subsequent nested PCR. RESULTS: In 16 biopsies (26,2 %) investigated (n = 61) a positive signal was noted after at least one PCR assay. In seven specimens direct sequencing was successful. CONCLUSIONS: The present study demonstrates that the established broad-spectrum PCR is a reliable method for detection of HPV-DNA. PMID- 17286243 TI - [Polyposis nasi--improvement in quality of life by the influence of leukotrien receptor antagonists]. AB - BACKGROUND: Sulfido-Leukotrienes are important inflammatory mediators of bronchial asthma, intolerance of acetylsalicylic acid (ASA), polyposis nasi and allergic rhinitis. Receptorantagonists like Montelukast constitute a well established asthma- and ASA intolerance-therapy. The aim of our study was to evaluate changes in patients Health-Related-Quality-of-Life (HRQL) during Montelukast-monotherapy of nasal polyposis. METHODS: The study was performed in a prospective, double blind and placebo-controlled matter. The study included 30 patients of our ENT outpatient's dept. (77 % male, mean age 49 yrs), suffering from nasal polyposis grade II to IV. Polyps were endoscopically graded, nasal Eosinophilic Cationic Protein (ECP) was measured, and HRQL-score was taken prior to and four weeks after Montelukast-(0 - 0 - 10 mg) compared to placebo. An established HRQL-questionnaire - including 25 items, summarized in 6 symptom groups - was used. Given was a symptom-score of 1 (not troubled) to 4 (extremely troubled). RESULTS: Patients treated with Montelukast improved their nasal symptoms (Delta HRQL-score 0.58 +/- 0.94, P < 0.01), practical problems (Delta HRQL-score 0.42 +/- 0.71, P < 0.05), headaches (Delta HRQL-score 0.38 +/- 0.56, P < 0.05), non-nasal symptoms (Delta HRQL-score 0.35 +/- 0.92, P < 0.05), sleep (Delta HRQL-score 0.26 +/- 0.71) and emotional problems (Delta HRQL-score 0.18 +/ 0.75). Intranasal ECP (Delta 210.67 ng/ml +/- 332.68) and polyp grading (Delta 0.72 +/- 1.77) tended to improve as well, but did not reach statistical significance. Patients treated with placebo revealed no significant changes neither in HRQL-score, ECP, nor polyp grading. CONCLUSIONS: Montelukast-therapy of nasal polyposis significantly improved patient's HRQL in 4 out of 6 symptom groups. Measuring HRQL proofed to constitute a more sensitive tool than looking at eosinophilic parameters of inflammation or polyp size. PMID- 17286244 TI - Bioluminescent signal system: bioluminescence immunoassay of pathogenic organisms. AB - The Ca(2+)-regulated photoprotein obelin has been examined as a label for bioluminescence immunoassay of infective agents. The hepatitis B virus (HbsAg) and the bacteria Escherichia coli and Shigella sonnei lipopolysaccharide (LPS) were chosen as model antigens. Chemically synthesized obelin-corresponding antibody conjugates were used in a solid-phase microplate immunoassay. The sensitivities achieved by the assay were 0.25 ng/mL for S. sonnei LPS and 0.375 ng/mL for HbsAg. A novel, filter-based immunoassay to determine bacterial admixtures in the environment was proposed. The NanoCeram filters were effectively applied to 'trap' and pre-concentrate pathogens from samples under study for the purposes of further detection and measurement of the absorbed material by bioluminescence immunoassay. PMID- 17286246 TI - Obsessive-compulsive characteristics in women who have recovered from bulimia nervosa. AB - OBJECTIVE: The goal of this study was to follow up on reports that obsessive compulsive characteristics, which are commonly elevated in bulimia nervosa (BN), may also be elevated in individuals who have recovered from BN (BN-R). METHOD: Self-ratings on the Maudsley Obsessional-Compulsive Inventory (MOCI), the Restraint Scale (a measure of dieting behavior related to weight concerns), and questionnaires reflecting eating disorder-related symptoms were evaluated for women who met criteria for BN (n = 25) or BN-R (n = 21) and were free of obsessive-compulsive disorder, and for healthy female controls (n = 28). RESULTS: MOCI scores for the BN-R group (5.5 +/- 5.4) were similar to those for the BN group (5.4 +/- 4.4) and were significantly elevated (p < 0.05, p < 0.02, respectively) in comparison to controls (2.5 +/- 1.9). Of note, MOCI scores for the BN-R group were significantly correlated with scores on the Restraint Scale (r = 0.60, p < 0.02). CONCLUSION: Further studies are needed to assess the relationship between elevated obsessive-compulsive characteristics and eating patterns in individuals recovered from BN. PMID- 17286245 TI - The expression level of luciferase within tumour cells can alter tumour growth upon in vivo bioluminescence imaging. AB - In vivo bioluminescence imaging is becoming a very important tool for the study of a variety of cellular and molecular events or disease processes in living systems. In vivo bioluminescence imaging is based on the detection of light emitted from within an animal. The light is generated as a product of the luciferase-luciferin reaction taking place in a cell. In this study, we implanted mice with tumour cells expressing either a high or a low level of luciferase. In vivo bioluminescence imaging was used to follow tumour progression. Repeated luciferin injection and imaging of high and low luciferase-expressing tumours was performed. While low luciferase-expressing tumours grew similarly to vector controls, growth of the high luciferase-expressing tumours was severely inhibited. The observation that a high level of luciferase expression will inhibit tumour cell growth when an animal is subjected to serial in vivo bioluminescence imaging is potentially an important factor in designing these types of studies. PMID- 17286247 TI - Positive association of the Disrupted-in-Schizophrenia-1 gene (DISC1) with schizophrenia in the Chinese Han population. AB - Disrupted-in-Schizophrenia-1 (DISC1) is located on 1q42.1, one of the most promising susceptibility loci in schizophrenia linkage studies. A non-synonymous genetic variation rs821616 (Ser704Cys) in DISC1, has recently been shown to be associated with schizophrenia in family-based study [Callicott et al. (2005); Proc Natl Acad Sci USA 102: 8627-8632]. In order to further confirm this issue, we examined four single nucleotide polymorphisms (SNPs) in a chromosomal region spanning 42 kb of this gene, namely rs821616, rs821597, rs4658971, and rs843979, in Chinese sample of 313 schizophrenia patients and 317 healthy controls. Our results showed that two SNPs had strong associations with schizophrenia (rs821616: Allele A > T, chi(2) = 7.8006, df = 1, P = 0.0052; Genotype, chi(2) = 7.7935, df = 2, P = 0.0203; rs821597: Allele A > G, chi(2) = 9.5404, df = 1, P = 0.0020; Genotype, chi(2) = 12.2780, df = 2, P = 0.0022). When haplotypes were constructed with two, three, and four markers, a number of haplotype combinations, especially those including rs821616 and rs821597, were significantly associated with schizophrenia. Furthermore, there was a strong evidence for association in a four-marker haplotype analysis (chi(2) = 7.686, df = 4, P = 0.005581, corrected P = 0.006199). Although the case-control and family based association studies both suggest that DISC1 gene may play a role in genetic susceptibility to schizophrenia, the risk haplotypic combinations have subtle differences in the two studies. Our findings provide further evidence for DISC1 as a predisposing gene involved in schizophrenia in the Chinese Han Population. PMID- 17286248 TI - A statistical model for inter-temporal causal dynamics of glucose production and disposal with insulin level in diabetic patients. AB - This paper provides a useful tool to examine inter-temporal behaviour in glucose and insulin level in diabetic patients. The primary thrust of this paper is to model inter-temporal causal dynamics of endogenous and ingested glucose production and disposal with insulin in diabetic patients. A short-run compartmental dynamics of glucose and insulin was introduced with their stochastic relationship through a vector autoregressive (VAR) scheme. This study also aims to develop glucose variability indices and test for their independence, homogeneity and symmetry at steady-state condition. The model also empirically identifies the significant prognostic factors and other exogenous variables affecting the dynamics. An empirical application provides more compelling evidence of such dynamics. The estimated model reconfirms the fact that pre prandial PM glucose level has statistically significant effects on post-prandial PM glucose level in diabetic patients. Also, pre-prandial PM insulin level shows a significant impact on post-prandial PM insulin in this study. In addition, results also indicate statistical significance of body mass index (BMI) and haemoglobin on post-prandial PM glucose level. It is interesting to note that the pattern of glucose variability indices in pre- and post-prandial AM time points is different from those at PM period. The results also show interdependence between the glucose variability indices. Only the pre- and post-meal PM variations of glucose are homogenous to its pre- and post-meal AM variations. PMID- 17286249 TI - Meta-analysis of randomized trials comparing anti-embolic devices with standard PCI for improving myocardial reperfusion in patients with acute myocardial infarction. AB - BACKGROUND: Failure to achieve adequate myocardial reperfusion often occurs during PCI in patients with STEMI. This is in part due to atheromatous and thrombotic distal embolization. Several anti-embolic devices have been developed to protect against distal embolization during percutaneous coronary interventions (PCI) to improve myocardial reperfusion and enhance event free survival. Evidence from current studies has not shown a consistent benefit, but anti-embolic devices continue to be used. METHODS: We conducted a systemic overview (meta-analysis) of randomized trials of thrombectomy or distal protection devices versus standard PCI to evaluate the effects of reducing distal embolization during PCI for native vessel acute myocardial infarction (AMI). We identified randomized trials by searching PubMed, OVID, the Cochrane databases, references of articles, and abstracts of conference proceedings (all from September 2000 to October 2005). Each trial tested the hypothesis that anti-embolic therapy would result in better clinical or angiographic results than standard PCI alone. RESULTS: Fourteen trials (n = 2630) were identified comparing a distal protection device or a thrombectomy device (n = 1320) versus standard PCI (n = 1310). When the studies were combined, primary endpoints of death or reinfarction were not improved by the use of anti-embolic devices (4% [52/1309] vs. 4.5% [59/1303], odds ratio [OR] 0.82 [95% CI 0.55 to 1.24, P= 0.35]). In subgroup analysis, analyzing the class of device separately, use of thrombectomy devices (4.4% [33/758 vs. 4.2% [32/763], OR 0.98 CI 0.53 to 1.83, P = 0.95]), and the use of distal protection device 3.5% [19/551] vs. 5% [27/540], OR 0.68 CI 0.37 to 1.23, P = 0.20]) during PCI for native vessel AMI did not improve the clinical outcome of death or reinfarction. The secondary endpoints of death, reinfarction, and major adverse cardiac events did not improve with the use of anti-embolic devices. CONCLUSION: The combined experience from randomized trials suggests that the use of anti embolic devices does not decrease early mortality or reinfarction during PCI for native vessel AMI. Whether their use improves longer term outcomes is unknown. Further research is needed to clarify the indication and optimal devices for anti embolic protection. PMID- 17286250 TI - Multiple left ventricular diverticuli in an asymptomatic adult: case report and review of the literature. AB - Left ventricular (LV) diverticulum is a rare congenital abnormality for which the etiology, management, and natural history are very poorly understood. Although most often observed as a single diverticulum, we report a case of multiple LV diverticuli in an asymptomatic adult referred for coronary evaluation due to an abnormal electrocardiogram. LV diverticuli are often associated with other congenital malformations, but can also be found in isolation. Cardiac magnetic resonance imaging provides enhanced ability to determine size, location, and morphological characteristics, which may improve lesion assessment and management. A review of the condition and reported complications is discussed. PMID- 17286252 TI - Improving outcomes for primary PCI. PMID- 17286251 TI - Sustained neocortical neurogenesis after neonatal hypoxic/ischemic injury. AB - OBJECTIVE: Neocortical neurons are sensitive to hypoxic-ischemic (H-I) injuries at term and their demise contributes to neurological disorders. Here we tested the hypothesis that the subventricular zone of the immature brain regenerates neocortical neurons, and that this response is sustained. METHODS: Systemic injections of 5-bromo-2'-deoxyuridine (BrdU) and intraventricular injections of replication-deficient retroviruses were used to label newly born cells, and confocal microscopy after immunofluorescence was used to phenotype the new cells from several days to several months after perinatal H-I in the postnatal day 6 rat. Quantitative polymerase chain reaction was used to evaluate chemoattractants, growth factors, and receptors. RESULTS: Robust production of new neocortical neurons after perinatal H-I occurs. These new neurons are descendants of the subventricular zone, and they colonize the cell-sparse columns produced by the injury to the neocortex. These columns are populated by reactive astrocytes and microglia. Surprisingly, this neuronogenesis is sustained for months. Molecular analyses demonstrated increased neocortical production of insulin-like growth factor-1 and monocyte chemoattractant factor-1 (but statistically insignificant production of erythropoietin, brain-derived neurotrophic factor, glial-derived neurotrophic factor, and transforming growth factor-alpha). INTERPRETATION: The young nervous system has long been known to possess a greater capacity to recover from injury than the adult system. Our data indicate that H-I injury in the neonatal brain initiates an enduring regenerative response from the subventricular zone. These data suggest that additional mechanisms than those previously surmised contribute to the remarkable ability of the immature brain to recover from injury. PMID- 17286253 TI - Social contexts, syndemics, and infectious disease in northern Aboriginal populations. AB - Until the last half of the 20th century, infectious diseases dominated the health profile of northern North American Aboriginal communities. Research on the 1918 influenza pandemic exemplifies some of the ways in which the social context of European contact and ensuing economic developments affected the nature of infectious disease ecology as well as the frequency and severity of the problem. To understand these impacts it is necessary to consider the web of interactions among multiple pathogens, the biology of the human host, and the social environment in which people lived. At the very least, an understanding of the history of the impact of infectious diseases on northern North American communities requires attention not only to potential interactions among cocirculating pathogens, but their links to key social, historical, and economic factors that exacerbated their adverse effects and contributed to excess mortality. PMID- 17286254 TI - Human cold adaptation: an unfinished agenda. AB - 1975 marked the end of a 20-year period of human biology research on physical environment. The focus then shifted from climatic adaptation to problems of nutrition, disease, and stress. However, many questions about human environmental patterns, especially in reference to their evolution, were abandoned rather than resolved. Assumptions about cold protective functions of low surface area/body mass ratio are entrenched in physical anthropology, despite lack of experimental validation. Since heat loss is controlled by vasoregulation and tissue insulation, a simple physics model of SA:mass may not apply. The issue merits investigation, as do the assumed thermal advantages of foreshortened extremities. Physiological assessment remains our primary research tool. In cold climate natives, elevated basal metabolic rates now appear to be genetically induced. During cold exposure, the body manages heat conservation through well known channels but also by specialized thermogenic functions such as metabolism in brown adipose tissue (BAT). The powerful protective capacity of BAT is largely unexplored either within or between populations of cold exposed human adults. An irony of our profession is that many biological variables seem to have minor effects when compared to behavioral cold protections. This is partly because biological anthropologists may have made incorrect assumptions about what most threatens the well being of cold climate people. Contrasts in environmental behaviors when comparing northern cultures such as Inuit, Athabaskan, and Norse are particularly instructive. Adaptations to life in the cold may ultimately reveal their secrets through biocultural research design modeling of environmental research. With both practical and theoretical gains still wide open, the field needs renewed attention from human biology. PMID- 17286259 TI - Adaptive dimensions of health research among indigenous Siberians. AB - Present evidence suggests that modern humans were the first hominid species to successfully colonize high-latitude environments (> or =55 degrees N). Given evidence for a recent (<200,000 years) lower latitude naissance of modern humans, the global dispersal and successful settlement of arctic and subarctic regions represent an unprecedented adaptive shift. This adaptive shift, which included cultural, behavioral, and biological dimensions, allowed human populations to cope with the myriad environmental stressors encountered in circumpolar regions. Although unique morphological and physiological adaptations among contemporary northern residents have been recognized for decades, human biologists are only now beginning to consider whether biological adaptations to regional environmental conditions influence health changes associated with economic modernization and lifestyle change. Recent studies have documented basal metabolic rates (BMRs) among indigenous Siberian populations that are systematically elevated compared to lower latitude groups; this metabolic elevation apparently is a physiological adaptation to cold stress experienced in the circumpolar environment. Important health implications of metabolic adaptation are suggested by research with the Yakut (Sakha), Evenki, and Buriat of Siberia. BMR is significantly positively correlated with blood pressure, independently of body size, body composition, and various potentially confounding variables (e.g., age and smoking). Further, this research has documented a significant negative association between BMR and LDL cholesterol, which remains after controlling for potential confounders; this suggests that high metabolic turnover among indigenous Siberians has a protective effect with regard to plasma lipid levels. These results underscore the importance of incorporating an evolutionary approach into health research among northern populations. PMID- 17286260 TI - Are the circumpolar Inuit becoming obese? AB - This paper reviews the ethnographic, historical, and recent epidemiological evidence of obesity among the Inuit/Eskimo in the circumpolar region. The Inuit are clearly at higher risk for obesity than other populations globally, if "universal" measures based on body mass index (BMI) and waist circumference and criteria such as those of WHO are used. Inuit women in particular have very high mean waist circumference levels in international comparisons. Given the limited trend data, BMI-defined obesity is more common today than even as recently as three decades ago. Inuit are not immune from the health hazards associated with obesity. However, the "dose-response" curves for the impact of obesity on metabolic indicators such as plasma lipids and blood pressure are lower than in other populations. Long-term, follow-up studies are needed to determine the metabolic consequences and disease risks of different categories of obesity. At least in one respect, the higher relative sitting height among Inuit, obesity measures based on BMI may not be appropriate for the Inuit. Ultimately, it is important to go beyond simple anthropometry to more accurate determination of body composition studies, and also localization of body fat using imaging techniques such as ultrasound and computed tomography. Internationally, there is increasing recognition of the need for ethnospecific obesity criteria. Notwithstanding the need for better quality epidemiological data, there is already an urgent need for action in the design and evaluation of community-based health interventions, if the emerging epidemic of obesity and other chronic diseases are to be averted. PMID- 17286261 TI - Genetic structure of circumpolar populations: a synthesis. AB - This article summarizes research conducted on the genetic structure of circumpolar populations of Alaska, Siberia, and the Aleutian Archipelago from 1977 to present. Three research programs are described: (1) 1977-1978, on the genetics of small, Yupik-speaking communities of St. Lawrence Island (Savoonga and Gambell) compared with Inupk communities of King Island and Wales, Alaska. This research, based on 25 standard protein and blood markers, demonstrated genetic discontinuity between the populations of the two language groups, patterns of gene flow, and the co-evolution of genes and languages in the Arctic. (2) 1989-1995, on the origins of Native American populations in Siberia. DNA was collected from two Evenki reindeer herding populations: Surinda and Poligus, a Ket community on the Stony Tunguska River, Sulamai, and a cattle-herding village from Gorno Altai, Mendur-Sokhon. Using an assortment of molecular markers, such as mitochondrial DNA, DNA fingerprints, and nonrecombining Y-chromosome markers, this research demonstrated the close genetic affinities among the Siberian and the Native American indigenous groups. (3) 1999 to present, on the origins of populations of the Aleutian Islands and their underlying genetic structure. A total of 11 inhabited islands from the Aleutian Archipelago were sampled and based on mtDNA sequences was shown to cluster tightly with Siberian Eskimo and Chukchi populations. Evidence of genetic drift through founder effect was demonstrated on Bering Island, where the D2 haplotype was fixed. Genetic discontinuity based on mtDNA was shown through SAMOVA between Kamchatkan and Aleut populations. An intimate relationship between geography and genetics through Mantel tests was observed for both Siberia (r = 0.55 P > 0.001) and the Aleutian Islands (r = 0.72 P > 0.000). The genetic structure of the populations of the Aleutian Archipelago most closely approximates the isolation-by-distance model. PMID- 17286263 TI - Human cold exposure, adaptation, and performance in high latitude environments. AB - Cold exposure is present to significant amounts in the everyday occupational and leisure time activities of circumpolar residents. A cross-sectional population study demonstrated that Finns reported being exposed to cold on average 4% of their total time. Factors modifying cold exposure are: age, gender, employment, education, health, and amount of physical exercise. Several symptoms and complaints are associated with wintertime cold exposure and start to appear more commonly when temperatures decrease below -10 degrees C. Urban circumpolar people do not evidently demonstrate cold acclimatization responses in terms of changes in thermoregulation, probably due to behavioral factors (adequate protective clothing, short cold exposures, and high housing temperatures). With regard to performance, we observed that moderate cold exposure, which may occur in everyday life, affects cognition negatively through the mechanisms of distraction and both positively and negatively through the mechanism of arousal (increased vigilance). It seems that especially simple cognitive tasks are adversely affected by cold, while in more complex tasks performance may even improve in mild or moderate cold. Repeated, short cold exposures in the laboratory, causing cold habituation responses, do not markedly improve neuromuscular or cognitive performance. The article discusses the functional significance of cold exposure, adaptation, and the specific environmental conditions and physiological mechanisms that affect behavior and performance in high latitude environments. PMID- 17286264 TI - Associated anomalies in multi-malformed infants with cleft lip and palate: An epidemiologic study of nearly 6 million births in 23 EUROCAT registries. AB - We studied 5,449 cases of cleft lip (CL) with or without cleft palate (CL/P) identified between 1980 and 2000 from the EUROCAT network of 23 registers (nearly 6 million births) in 14 European countries. We investigated specific types of defects associated with clefts. Among CL/P cases (prevalence = 9.1 per 10,000), 1,996 (36.6%) affected only the lip (CL) and 3,453 (63.4%) involved CL and palate (CLP). A total of 3,860 CL/P cases (70.8%) occurred as isolated anomalies and 1,589 (29.2%) were associated with other defects such as multiple congenital anomalies of unknown origin (970), chromosomal (455) and recognized syndromes (164). Associated malformations were more frequent in infants who had CLP (34.0%) than in infants with CL only (20.8%). Among multi-malformed infants, 2 unrelated anomalies were found in 351 cases, 3 in 242 cases, and 4 or more in 377 cases. Among 5,449 CL/P cases, 4,719 were live births (LB) (86.6%), 203 stillbirths (SB) (3.7%), while 508 (9.3%) were terminations of pregnancy (ToP). CL/P occurred significantly more frequently in males (M/F = 1.70), especially among total isolated cases (M/F = 1.87) and CLP isolated cases (M/F = 1.92). The study confirmed that musculoskeletal, cardiovascular, and central nervous system defects are frequently associated with CL/P. An association with reduction anomalies of the brain was found. This association suggests that clinicians should seek to identify structural brain anomalies in these patients with CL/P as the potential functional consequences may be important for rehabilitation and clinical management. PMID- 17286265 TI - Increasing knowledge of PTEN germline mutations: Two additional patients with autism and macrocephaly. AB - Recently, Butler et al. [2005; J Med Genet 42:318-321] reported the presence of heterozygous germline mutations in the PTEN tumor suppressor gene in three children with autism and macrocephaly. Here, we report the presence of PTEN mutations in two additional unrelated children with macrocephaly and autism. Our findings extend those of Butler et al. and suggest that PTEN gene sequencing should be included in the genetic evaluation of this subset of autistic individuals. PMID- 17286266 TI - An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. AB - Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial liver sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the liver acinus. This unit consisted of a cord of hepatocytes (50 x 30 x 500 microm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC(50) of 334 +/- 41 microM after 24 h. PMID- 17286267 TI - An aerobic sequencing batch reactor for 2,4,6-trinitrophenol (picric acid) biodegradation. AB - A bench scale sequencing batch reactor (SBR) was designed and tested for degradation of 2,4,6-trinitrophenol (TNP) or picric acid-contaminated wastewater or groundwater. Under varying temperatures (25, 15 and 10 degrees C) and influent concentrations (40-200 mg/L TNP) a stable biomass was developed that was consistently capable of degrading the explosive compound to below regulatory drinking water limits (0.057 mg/L). The reactor was initially seeded with a nitroaromatic and nitramine degrading isolate Rhodococcus opacus strain JW01. Kinetic growth modeling was conducted revealing micro(max) values at 25, 15 and 10 degrees C of 0.14, 0.08 and 0.04 d(-1), while the modeled K(s) values were 0.68, 1.11 and 1.24 mg/L, respectively. Overall TNP removal efficiency in the SBR was on average > 99.9% over the 2000 hours of operation. Removal of TNP to below drinking water standards, with low residual dissolved carbon and significant release of nitrogen from the parent compound was accomplished. PMID- 17286268 TI - Trehalose and calcium exert site-specific effects on calmodulin conformation in amorphous solids. AB - We have adapted hydrogen/deuterium (H/D) exchange with electrospray ionization mass spectrometry (ESI-MS) to study protein conformation and excipient interactions in lyophilized solids. Using calmodulin (CaM, 17 kD) as a model protein, we demonstrate that trehalose and calcium exert site-specific effects on protein conformation. The effects of calcium are observed primarily in the calcium binding loops, while those of trehalose are observed primarily in non terminal alpha-helical regions. To our knowledge, this is the first demonstration of site-specificity in the effects of excipients on protein structure in the solid state, and of the utility of H/D exchange with ESI-MS to characterize proteins in amorphous solids. PMID- 17286269 TI - Ultrastructural studies of midgut epithelium formation in Lepisma saccharina L. (Insecta, Zygentoma). AB - At the end of embryogenesis of Lepisma saccharina L. (Insecta, Zygentoma), when the stomodaeum and proctodaeum are completely formed, the midgut epithelium is replaced by the primary midgut, a yolk mass is surrounded by a cell membrane. Midgut epithelium formation begins in the 1st larval stage. Energids migrate toward the yolk periphery and aggregate just beneath the cell membrane. They are gradually enclosed by cell membrane folds of the primary midgut. Single cells are formed. Succeeding energids join just formed cells. Thus, groups of cells, regenerative cell groups, are formed. Their number gradually increases. The external cells of the regenerative cell groups transform into epithelial cells and their basal regions spread toward the next regenerative cell groups. Epithelial cells of neighboring regenerative cell groups join each other to form the epithelium. At the end of the 2nd larval stage, just before molting, degeneration of newly the formed epithelium begins. Remains of organelles and basal membrane occur between the regenerative cell groups. The new epithelium is formed from the regenerative cell groups, which are now termed stem cells of the midgut epithelium. PMID- 17286270 TI - Anaerobic methanethiol degradation in upflow anaerobic sludge bed reactors at high salinity (> or =0.5 M Na(+)). AB - The feasibility of anaerobic methanethiol (MT) degradation at elevated sodium concentrations was investigated in a mesophilic (30 degrees C) lab-scale upflow anaerobic sludge bed (UASB) reactor, inoculated with estuarine sediment originating from the Wadden Sea (The Netherlands). MT was almost completely degraded (>95%) to sulfide, methane and carbon dioxide at volumetric loading rates up to 37 mmol MT x L(-1) x day(-1), 0.5 M sodium (NaCl or NaHCO(3)) and between pH 7.3 and 8.4. Batch experiments revealed that inhibition of MT degradation started at sodium (both NaCl and NaHCO(3)) concentrations exceeding 0.8 M. Sulfide inhibited MT degradation already around 3 mM (pH 8.3). PMID- 17286271 TI - SERCA pump isoforms: their role in calcium transport and disease. AB - The sarcoendoplasmic reticulum (SR) calcium transport ATPase (SERCA) is a pump that transports calcium ions from the cytoplasm into the SR. It is present in both animal and plant cells, although knowledge of SERCA in the latter is scant. The pump shares the catalytic properties of ion-motive ATPases of the P-type family, but has distinctive regulation properties. The SERCA pump is encoded by a family of three genes, SERCA1, 2, and 3, that are highly conserved but localized on different chromosomes. The SERCA isoform diversity is dramatically enhanced by alternative splicing of the transcripts, occurring mainly at the COOH-terminal. At present, more than 10 different SERCA isoforms have been detected at the protein level. These isoforms exhibit both tissue and developmental specificity, suggesting that they contribute to unique physiological properties of the tissue in which they are expressed. The function of the SERCA pump is modulated by the endogenous molecules phospholamban (PLB) and sarcolipin (SLN), expressed in cardiac and skeletal muscles. The mechanism of action of PLB on SERCA is well characterized, whereas that of SLN is only beginning to be understood. Because the SERCA pump plays a major role in muscle contraction, a number of investigations have focused on understanding its role in cardiac and skeletal muscle disease. These studies document that SERCA pump expression and activity are decreased in aging and in a variety of pathophysiological conditions including heart failure. Recently, SERCA pump gene transfer was shown to be effective in restoring contractile function in failing heart muscle, thus emphasizing its importance in muscle physiology and its potential use as a therapeutic agent. PMID- 17286272 TI - Safety factor for neuromuscular transmission at type-identified diaphragm fibers. AB - The safety factor (SF) for neuromuscular transmission varies across limb muscles of different fiber-type composition. Using intracellular recordings in rat diaphragm fibers, we found that SF varies across muscle fiber types (even within a single muscle), being larger for type IIx or IIb fibers than for type I or IIa fibers. Fiber-type differences in activation history or mechanical load may contribute to differences in SF and are important determinants of neuromuscular plasticity. PMID- 17286273 TI - Genetic engineering, expression, and activity of a fusion protein of a human neurotrophin and a molecular Trojan horse for delivery across the human blood brain barrier. AB - Neurotrophins, such as brain derived neurotrophic factor (BDNF), do not cross the blood-brain barrier (BBB). Certain monoclonal antibodies (MAb) to the human insulin receptor (HIR) do cross the BBB via receptor-mediated transport, and can act as a molecular Trojan horse to ferry across the BBB an attached drug. A genetically engineered fusion protein was produced whereby the amino terminus of human BDNF is fused to the carboxyl terminus of the heavy chain of a chimeric HIRMAb. The HIRMAb-BDNF fusion protein reacted equally with antibodies to human IgG and BDNF. The bi-functionality of the fusion protein was retained as the affinity of the fusion protein for the HIR was identical to that of the chimeric HIRMAb, and the affinity of the fusion protein for the trkB receptor was identical to that of BDNF. The fusion protein was equi-potent with BDNF in a neuroprotection assay in human neural cells. The pharmacokinetics (PK) of the fusion protein was examined in the adult Rhesus monkey. The mean residence time (MRT) of the fusion protein in blood was >100-fold longer than the MRT of BDNF. Therapeutic levels of BDNF were produced in primate brain following the intravenous administration of the fusion protein. A fusion protein tandem vector was engineered that allowed for isolation of a CHO cell line that produced the fusion protein at high levels in serum free medium. Neurotrophins, such as BDNF, can be re-formulated to enable these molecules to cross the human BBB, and such fusion proteins represent a new class of human neurotherapeutics. PMID- 17286274 TI - Drug-polymer microparticles produced by supercritical assisted atomization. AB - The supercritical assisted atomization (SAA) was proposed as a new technique to produce composite microparticles for drug controlled release. Ampicillin trihydrate and chitosan were selected as model drug and carrier, respectively, and 1% v/v acetic acid aqueous solution was used as solvent. The effect of the polymer/drug ratio on particle morphology and drug release rate was evaluated. SEM analysis indicated that non-coalescing spherical microparticles formed by chitosan/ampicillin were produced by SAA. All coprecipitates produced have a sharp particle distribution, with diameters ranging between about 0.1 and 6 microm. SAA composite microparticles were characterized by X-ray, DSC, EDX and UV vis analysis. A solid solution of the chitosan and ampicillin was produced and a stabilizing effect of the polymer on the drug has resulted that protects ampicillin from thermal degradation. A prolonged release from SAA coprecipitates with respect to raw drug and physical mixtures of chitosan and ampicillin was obtained; moreover, the polymer/drug ratio has revealed to be a controlling parameter for drug release. Drug release mechanisms characteristic of swelling controlled systems were observed, with ampicillin release depending on both relaxation and diffusive mechanisms. An empirical binomial equation was used to describe experimental data, showing a fair good agreement with ampicillin release data if both the relaxational and the diffusional parameters are function of the polymer/drug ratio. PMID- 17286275 TI - Intercenter variation in initial management of children with Crohn's disease. AB - BACKGROUND: Variation in care is a ubiquitous feature of medical practice and may lead to significant differences in health care costs, quality, and outcomes. We undertook this study to determine the extent of intercenter variation in the initial management of children newly diagnosed with Crohn's disease. METHODS: We analyzed the utilization of 5 classes of medication (immunomodulators, prednisone, antibiotics, 5-aminosalicylates, and infliximab) among 311 children with newly diagnosed Crohn's disease followed at 10 North American pediatric gastroenterology centers. Multivariate logistic regression was used to compare the utilization rate of each class of medication at each of the 10 centers, adjusting for potential confounders including patient age, sex, race, disease severity, and anatomic location of disease. RESULTS: Median utilization of each class of medication was: immunomodulators, 56% (range 29%-97%); prednisone, 78% (range 32%-88%); antibiotics, 29% (range 11%-68%); 5-aminosalicylates, 63.5% (range 18%-92%); and infliximab, 7.5% (range 3%-21%). Each of these treatments showed statistically significant intercenter variation in utilization (P < 0.001 for immunomodulators, prednisone, antibiotics, and 5-ASA; P = 0.02 for infliximab). After adjusting for the demographic and clinical factors listed above, intercenter variation remained significant; however, the low utilization of infliximab precluded multivariate analysis. CONCLUSIONS: Widespread intercenter variation in the medical management of newly diagnosed children with Crohn's disease was observed, even after adjusting for possible differences in case mix between institutions. This variation may lead to unintended differences in health care costs and outcomes. PMID- 17286276 TI - A co-clustering model involving alpha5beta1 integrin for the biological effects of GPI-anchored human carcinoembryonic antigen (CEA). AB - CEA functions as an intercellular adhesion molecule and is up-regulated in a wide variety of human cancers, including colon, breast and lung. Its over-expression inhibits cellular differentiation, blocks cell polarization, distorts tissue architecture, and inhibits anoikis of many different cell types. Here we report results concerning the molecular mechanism involved in these biological effects, where relatively rapid molecular changes not requiring alterations in gene expression were emphasized. Confocal microscopy experiments showed that antibody mediated clustering of a deletion mutant of CEA (DeltaNCEA), normally incapable of self binding and clustering, led to the co-localization of integrin alpha5beta1 with patches of DeltaNCEA on the cell surface. Activation of alpha5, as defined by an anti-alpha5 mAb-sensitive increase in cell adhesion to immobilized fibronectin, and an increased binding of soluble fibronectin to cells, was also observed. This was accompanied by the recruitment of integrin linked kinase (ILK), protein kinase B (PKB/Akt), and the mitogen-activated protein kinase (MAPK) to membrane microdomains and the phosphorylation of Akt and MAPK. Inhibition of PI3-K and ILK, but not MAPK, prevented the alpha5beta1 integrin activation. Conversely, anti-alpha5 antibody inhibited the PI3-K mediated activation of Akt, implying the involvement of outside-in and inside-out signaling in integrin activation. Therefore we propose that CEA-mediated signaling involves clustering of CEA and co-clustering and activation of the alpha5beta1 and associated specific signaling elements on the internal surfaces of membrane microdomains. These changes may represent a molecular mechanism for the biological effects of CEA. PMID- 17286277 TI - Gender and endogenous levels of estradiol do not influence adult hippocampal neurogenesis in mice. AB - In several species, including rat and vole, the proliferation of new neurons in the adult dentate gyrus (DG) subgranular zone (SGZ) is influenced by both gender and endogenous levels of the gonadotropic steroid hormone estradiol. However, little is known about how adult neurogenesis is regulated by these factors in the mouse. We report here that adult C57BL/6 mice do not have gender differences in hippocampal proliferation or neurogenesis. In addition, the production of new SGZ cells in female mice was not influenced by estrous cycle or after ovariectomy, suggesting that fluctuations in endogenous estradiol levels do not alter adult neurogenesis in the mouse. Both male and female mice had a greater number of BrdU immunoreactive SGZ cells following chronic treatment with fluoxetine. This demonstrates a parallel proliferation response in both genders, and opens avenues for addressing the neurogenesis hypothesis of depression in female rodents. These findings underscore a distinct regulation of adult neurogenesis in mice vs. other rodents, and are discussed in regard to their implications for the study of adult hippocampal neurogenesis. PMID- 17286278 TI - Selective cholinergic depletion of the hippocampus spares both behaviorally induced Arc transcription and spatial learning and memory. AB - We demonstrated previously that when hippocampal-dependent learning and plasticity are compromised by fornix lesions, behaviorally induced expression of the immediate early gene, Arc, is correspondingly low. The medial septum and the vertical diagonal band are major sources of subcortical afferents that innervate the hippocampus via the fornix. Here we assessed the specific contribution of cholinergic afferents from these regions to the impairments in spatial learning and behavioral induction of Arc transcription produced by fornix lesions. The immunotoxin, 192 IgG-saporin, was used to produce selective lesions of cholinergic cell bodies in the medial septum and vertical diagonal band. Rats were then trained on both cued and spatial delayed match-to-place tasks in a radial arm water maze. Animals with 192 IgG-saporin lesions learned both cue and place discrimination tasks in the water maze normally, and showed only a mild and transient impairment when switching from the cued to the spatial version of the task. Following behavioral testing, rats explored two novel environments sequentially in a setting known to induce Arc expression in hippocampal pyramidal neurons. In marked contrast to the effects of complete fornix transection, quantitative in situ autoradiography revealed no differences in Arc mRNA expression between sham and lesion animals in CA1, CA3 or stratum radiatum. The conclusion from these data is that cholinergic deafferentation alone cannot account for the spatial learning deficits or impaired behavioral induction of Arc transcription produced by fornix lesions. PMID- 17286279 TI - Dissociation of growth arrest and CYP24 induction by VDR ligands in mammary tumor cells. AB - Murine mammary tumor cells with differential vitamin D receptor (VDR) expression were used to study the mechanisms of growth inhibition by vitamin D steroids. In VDR-expressing WT145 cells, 1,25D and its synthetic analog EB1089 induce growth arrest and transcriptionally upregulate the well-characterized VDR target gene CYP24. 1,25D also induces apoptosis in WT145 cells through activation of initiator and executioner caspases and the calcium-dependent protease calpain. We also demonstrate that WT145 cells express CYP27B1, the enzyme that converts 25 hydroxyvitamin D(3) (25D) to 1,25D, and that 25D inhibits growth of these cells but does not trigger apoptosis or induce CYP24 expression. Comparative studies were conducted in KO240 cells, which were derived from VDR knockout mice and found to retain expression of CYP27B1. KO240 cells were not growth inhibited nor rendered apoptotic by any of the tested vitamin D compounds. These data conclusively demonstrate that VDR mediates the anti-proliferative and pro apoptotic effects of vitamin D metabolites and analogs, but that the potency of a vitamin D compound to induce the VDR target gene CYP24 does not accurately predict its potency in mediating growth regulation. PMID- 17286280 TI - Suppression of growth and cancer-induced angiogenesis of aggressive human breast cancer cells (MDA-MB-231) on the chorioallantoic membrane of developing chicken embryos by E-peptide of pro-IGF-I. AB - E-peptide of the pro-Insulin-like growth factor-I (pro-IGF-I) is produced from pre-pro-IGF-I by proteolytic cleavage in the post-translational processing. Previous in vitro studies conducted in our laboratory showed that Ea4-peptide of rainbow trout (rt) pro-IGF-I or Eb-peptide of human (h) pro-IGF-I exhibited activities including induction of morphological differentiation, inhibition of anchorage-independent cell growth and suppression of invasion of several well established human cancer cell lines such as MDA-MB-231, HT-29, SK-N-F1, and HepG 2 (Chen et al. [2002] Gen Comp Endocrinol 126:342-351; Kuo and Chen [2002] Exp Cell Res 280:75-89). Seeding of aggressive human breast cancer cells, MDA-MB-231, on the chorioallantoic membrane (CAM) of 5 days old chicken embryos resulted in rapid growth and invasion of the cells and induction of blood vessel formation around the MDA-MB-231 cell mass in the chicken embryos. The invasion of MDA-MB 231 cells in the chicken embryos was further confirmed by immunocytochemistry. The rapid growth and invasion of MDA-MB-231 cells and the induction of blood vessel formation by MDA-MB-231 cells on chicken CAM are inhibited by treatment with a single or multiple doses of rtEa4- or hEb-peptide. Furthermore, a dose dependent inhibition of angiogenesis by rtEa4- or hEb-peptide was also demonstrated by the chicken CAM assay. Results of microarray analysis of human gene chips (containing 9,500 unique cDNA clones) and confirmation by comparative real-time RT-PCR analysis showed that a group of genes related to cancer cell activities are up- or down-regulated in MDA-MB-231 cells transfected with a rtEa4 peptide gene. Together these results confirm the anti-tumor activity of rtEa4- and hEb-peptides, and further suggest that these peptides could be developed as therapeutics for treating human cancers. PMID- 17286281 TI - Subcellular localization of ankyrin repeats cofactor-1 regulates its corepressor activity. AB - The ankyrin repeats cofactor-1 (ANCO-1) was recently identified as a novel nuclear receptor corepressor that regulates receptor-mediated transcription through interactions with p160 coactivators and histone deacetylases. Interestingly, exogenously expressed ANCO-1 is localized at distinct subnuclear domains. The relevance of these subnuclear domains and the mechanisms of nucleocytoplasmic translocation of ANCO-1 have not been determined. We report here the identification of an N-terminal signaling motif that is essential for both nuclear/subnuclear localization and transcription corepressor function of ANCO-1. This N-terminal motif at residues 80-86 of ANCO-1 constitutes a classical nuclear localization signal (NLS1). Disruption of NLS1 causes complete cytoplasmic accumulation of the full-length ANCO-1, and abolishes its corepressor function on receptor-mediated transcription. A second NLS (NLS2) is found at the C-terminal residues 2384-2390; however, its disruption abolishes only nuclear localization of isolated C-terminal fragments. We also identify a leucine-rich nuclear export signal (NES) at residues 2415-2424 of ANCO-1, and show that both the NLSs and NES sequences are capable of mediating nuclear import and export of heterologous protein, respectively. In addition, attachment of the NES sequence to a transcription factor impairs its activation function. These results suggest that ANCO-1 subnuclear localization is regulated by both nuclear import and export signals, and that proper subcellular localization of ANCO-1 is essential for its corepressor function. PMID- 17286282 TI - Upregulation of retinoic acid receptor-beta by the epidermal growth factor receptor inhibitor PD153035 is not mediated by blockade of ErbB pathways. AB - Inhibiting epidermal growth factor-receptor (ErbB-1) represents a powerful anticancer strategy. Activation of retinoid pathways is also in development for cancer treatment. Retinoic acid receptor-beta-the tumor suppressor and main retinoid mediator--is silenced in many tumors. The ErbB-1 inhibitor PD153035 cooperates with retinoic acid during growth inhibition and induces retinoic acid receptor-beta suggesting that ErbB-1 controls retinoic acid receptor-beta. However, here we demonstrate that ErbB pathways are not involved in PD153035 mediated retinoic acid receptor-beta-upregulation. PD153035 inhibits ErbB-1 phosphorylation, whereas its derivative EBE-A22 is inactive. Yet both inhibit cell growth and upregulate retinoic acid receptor-beta in ErbB-1-overexpressing (MDA-MB-468), moderately expressing (OVCAR-3), ErbB-1-negative (MDA-MB-453) or ErbB-negative cells (CEM, Jurkat). Both bind DNA, whereas the closely related ErbB-1 inhibitors AG1478 and ZD1839, which are inactive on retinoic acid receptor beta, do not significantly bind DNA. None of the other ErbB-1/ErbB-2 inhibitors tested (RG-14620, LFM-A12, AG879, AG825) affect retinoic acid receptor-beta. PD153035 decreases methylation of the retinoic acid receptor-beta2 promoter. In OVCAR-3, it stimulates dislodgement of histone deacetylase 1 from the promoter and acetylation of histones H3 and H4. Consequently, PD153035 facilitates recruitment of RNA polymerase II to the promoter and stimulates transcriptional activity. Moreover, PD153035 increases the retinoic acid receptor-beta mRNA half life. No other retinoid receptor, nor estrogen receptor-alpha, nor RASSF1A is upregulated by PD153035. Thus PD153035 induces retinoic acid receptor-beta by ErbB-independent transcriptional and post-transcriptional mechanisms. This report highlights a triple action for an ErbB-1 inhibitor (ErbB-1 inhibition, DNA intercalation, retinoic acid receptor-beta-induction). Such multitargeting drugs bear great potential for cancer treatment. PMID- 17286283 TI - Walking through the protein sequence space: towards new generation of the homology modeling. AB - A new method is proposed to reveal apparent evolutionary relationships between protein fragments with similar 3D structures by finding "intermediate" sequences in the proteomic database. Instead of looking for homologies and intermediates for a whole protein domain, we build a chain of intermediate short sequences, which allows one to link similar structural modules of proteins belonging to the same or different families. Several such chains of intermediates can be combined into an evolutionary tree of structural protein modules. All calculations were made for protein fragments of 20 aa residues. Three evolutionary trees for different module structures are described. The aim of the paper is to introduce the new method and to demonstrate its potential for protein structural predictions. The approach also opens new perspectives for protein evolution studies. PMID- 17286284 TI - Non-heme iron through the three domains of life. AB - Metalloproteins are proteins capable of binding one or more metal ions, which are often required for their biological function or for regulation of their activities or for structural purposes. In high-throughput genome-level protein investigation efforts, such as Structural Genomics, the systematic experimental characterization of metal-binding properties (i.e. the investigation of the metalloproteome) is not always pursued, and remains far from trivial. In the present work we have applied a bioinformatic approach to investigate the occurrence of (putative) non-heme iron-binding proteins in 57 different organisms spanning the entire tree of life. It is found that the non-heme iron-proteome constitutes between 1% and 10% of the entire proteome of an organism. However, the iron-proteome constitutes a higher fraction of the proteome in archaea (on average 7.1% +/- 2.1%) than in bacteria (3.9% +/- 1.6%) and in eukaryota (1.1% +/ 0.4%). The analysis of the function of each putative iron-protein identified suggests that extant organisms have inherited the large majority of their iron proteome from the last common ancestor. PMID- 17286285 TI - Simple solvation potential for coarse-grained models of proteins. AB - We formulate a simple solvation potential based on a coarsed-grained representation of amino acids with two spheres modeling the C(alpha) atom and an effective side-chain centroid. The potential relies on a new method for estimating the buried area of residues, based on counting the effective number of burying neighbors in a suitable way. This latter quantity shows a good correlation with the buried area of residues computed from all atom crystallographic structures. We check the discriminatory power of the solvation potential alone to identify the native fold of a protein from a set of decoys and show the potential to be considerably selective. PMID- 17286286 TI - Three-dimensional imaging is here and now: time to prove its relevance. PMID- 17286287 TI - Peptide drug delivery strategies for the treatment of diabetes. AB - Drug delivery strategies for diabetes have included a wide range of scientific and engineering approaches, including molecular design, formulation and device design. Molecular engineering has resulted in modified pharmacokinetics, such as rapid-acting or slow-release analogs of insulin. Long-acting insulin formulations are designed to meet the body's basal needs, whereas rapid-acting insulin formulations are designed to cover mealtime glucose spikes. Furthermore, the discovery of new therapeutic biomolecules, which like insulin need to be injected, will drive the need for more flexible and universally applicable delivery systems. Formulation design, such as particle engineering, can be used to modify pharmacokinetic profiles. In general, suspension formulations of insulin commonly demonstrate reduced solubility and result in sustained release. Similarly, depot injections can result in precipitation of insulin at the site of injection, again resulting in lower solubility and sustained release. Particle engineering also has been applied to pulmonary formulations for delivery to the deep lung. The creation of novel drug delivery methods for the treatment of diabetes should remove barriers to insulin therapy and increase patient acceptance and compliance. Eliminating routine injections with needle-free injectors, insulin pumps, inhalation, buccal sprays, intra-nasal delivery, and transdermal patches may offer increasingly attractive alternatives. PMID- 17286288 TI - Ex vivo study of transdermal permeation of four diclofenac salts from different vehicles. AB - The ex vivo permeation of diclofenac was studied using four different salts (sodium, potassium, diethylamine, and epolamine) dissolved in four different solvents (water, propylene glycol (PG), Transcutol, and oleic acid (OA)) as donor phases through a human skin membrane. The four salts show different solubility values and different behavior in the four solvents, which are also permeation enhancers and this fact further is connected to the permeation results. The same order of magnitude of fluxes through the membrane as those previously reported for acidic diclofenac released from buffer solutions of pH >7 were found, taking into account differences originated by different membranes and other parameters tested in the experiments. Saturation concentration for the four salts in different solvents, necessary to calculate permeation coefficients, was critically evaluated; a short discussion made it possible to explain that corrections in the solubility values must be considered, related to the complex behavior in solution of these salts. Statistical processing of the experimental data suggests that differences between the four salts in promoting absorption of the drug is unproven; while differences are evident between the solvents, water is the most effective enhancing vehicle. Aqueous formulations containing diclofenac salt with an organic base appear to be the best combination to promote permeation in topical applications. PMID- 17286289 TI - Structure-interaction relationships between the bile acid GCA and pharmaceuticals using multivariate data analysis and capillary electrophoresis. AB - Capillary electrophoresis (CE) has been used in an interaction study of 66 pharmaceutical compounds with the bile acid glycocholate (GCA). The developed method proved to have a high precision in its ability to determine the mobility of drugs in buffer and buffer bile acids solutions. The relationship between solute structure and interaction with GCA was studied using two-dimensional descriptors with the in-house software SELMA and a three-dimensional model (quantum mechanical descriptors) in combination with the experimental CE interaction data. The multivariate analysis method used was projection to latent structures by means of partial least squares (PLS). Two selections of training and test set were used for evaluation of a two-class model on interaction data. In the first selection all observations were used for training set, for example, creating a model, and re-predicting the observations on the model. A successful prediction on 85% of the drugs was observed using this model. The second selection used the 21 first tested compounds in the training set, where 78% of the compounds were correctly predicted using the two-dimensional model (SELMA) on the remaining 45 compounds and, respectively, 82% using the three-dimensional (quantum mechanical) model. Analysis of the impact of the descriptors showed that descriptors relating to hydrophobicity have a large positive effect on the interaction. Descriptors relating to polar properties have a pronounced negative effect on the interaction of drugs with bile acids. PMID- 17286290 TI - Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on stability (I): stability of a monoclonal antibody. AB - The present study was conducted to investigate the impact of drying method and formulation on the storage stability of IgG1. Formulations of IgG1 with varying levels of sucrose with and without surfactant were dried by different methods, namely freeze drying, spray drying, and foam drying. Dried powders were characterized by thermal analysis, scanning electron microscopy, specific surface area (SSA) analysis, electron spectroscopy for chemical analysis (ESCA), solid state FTIR, and molecular mobility measurements by both isothermal calorimetry and incoherent elastic neutron scattering. Dried formulations were subjected to storage stability studies at 40 degrees C and 50 degrees C (aggregate levels were measured by size exclusion chromatography initially and at different time points). Both drying method and formulation had a significant impact on the properties of IgG1 powders, including storage stability. Among the drying methods, SSA was highest and perturbations in secondary structure were lowest with the spray-dried preparations. Sucrose-rich foams had the lowest SSA and the lowest protein surface accumulation. Also, sucrose-rich foams had the lowest molecular mobility (both fast dynamics and global motions). Stability studies showed a log-linear dependence of physical stability on composition. Preparations manufactured by "Foam Drying" were the most stable, regardless of the stabilizer level. In protein-rich formulations, freeze-dried powders showed the poorest storage stability and the stability differences were correlated to differences in secondary structure. In stabilizer-rich formulations, stability differences were best correlated to differences in molecular mobility (fast dynamics) and total protein surface accumulation. PMID- 17286291 TI - Dendrimers as a carrier for pulmonary delivery of enoxaparin, a low-molecular weight heparin. AB - This study was designed to test the hypothesis that positively charged dendrimers form a complex with enoxaparin, a low-molecular weight heparin (LMWH), and that the resulting drug-dendrimer complex is effective in preventing deep vein thrombosis after pulmonary administration. Fourier Transform Infrared (FTIR) spectroscopy and the azure A assay were used to evaluate interactions between dendrimers and enoxaparin. The efficacy of polyamidoamine (PAMAM) dendrimers in enhancing pulmonary absorption of enoxaparin was studied by administering enoxaparin-dendrimer formulations into the lungs of anesthetized rats and monitoring drug absorption by measuring plasma anti-factor Xa activity. The optimized formulations were evaluated for their efficacy in preventing deep vein thrombosis in a rodent model. The safety of the formulations was tested by studying their effects on mucociliary transport rate (MTR) in a frog palate model and by measuring injury markers in rat bronchoalveolar fluid. The FTIR data and azure A assay revealed ionic interactions between the amino groups of cationic dendrimers and the carboxylic and sulfate groups of enoxaparin. Positively charged dendrimers increased the relative bioavailability of enoxaparin by 40%, while a negatively charged dendrimer had no effect. Formulations containing 1% G2 or 0.5% G3 PAMAM dendrimer plus enoxaparin were as efficacious in preventing deep vein thrombosis in a rat model as subcutaneously administered enoxaparin. The formulations did not adversely affect the MTR or produce extensive damage to the lungs. Positively charged dendrimers are a suitable carrier for pulmonary delivery of enoxaparin. They enhance pulmonary absorption of LMWH probably by reducing negative surface charge density of the drug molecule. PMID- 17286292 TI - Placental growth patterns affect birth weight for given placental weight. AB - BACKGROUND: An important contributor to fetal growth is growth of the placenta, the fetus' sole source of nutrients and oxygen. Here we use placental growth measures (larger and smaller disk diameters, reflecting the laterally expanding chorionic plate, and disk thickness) to test the hypothesis that placental growth patterns, while associated with placental weight and birth weight, measure placental functional efficiency, and will have independent effects on the feto placental weight ratio (FPR). METHODS: Placental measures were available from 23,313 participants in the Collaborative Perinatal Project delivered between 34 and 43 completed weeks. Continuous variables were analyzed by regression for associations with placental weight, birth weight, and FPR, to further explore effects of placental growth patterns on the FPR (lateral chorionic plate growth and chorionic disk thickness were grouped as low, normal, and high values). The relationships of the nine resultant combinations of placental growth categories to the FPR using birth weight adjusted for gestational age, infant gender, parity, and African American race were analyzed (ANOVA). RESULTS: As chorionic disk area and thickness increased, birth weight and placental weight increased, and the FPR decreased (each p < .0001) after adjustment for gestational age, parity, race, and infant gender. Small, thin placental disks had an adjusted FPR of 8.46; the largest, thickest placentas had an adjusted FPR of 6.33. The nine categories of FPRs were significantly different, consistent with chorionic plate area and disk thickness combining to determine the FPR. CONCLUSIONS: Patterns of placental growth, relating to different functional dimensions of the placenta, deliver a different birth weight for a given placental weight. PMID- 17286293 TI - Nano-level detection of naltrexone hydrochloride in its pharmaceutical preparation at Au microelectrode in flowing solutions by fast fourier transforms continuous cyclic voltammetry as a novel detector. AB - An easy and fast Fourier transform continuous cyclic voltammetric technique for monitoring of ultra trace amounts of naltrexone in a flow-injection system has been introduced in this work. The potential waveform, consisting of the potential steps for cleaning, stripping and potential ramp, was continuously applied on an Au disk microelectrode (with a 12.5 microm in radius). The proposed detection method has some of advantages, the greatest of which are as follows: first, it is no more necessary to remove oxygen from the analyte solution and second, this is a very fast and appropriate technique for determination of the drug compound in a wide variety of chromatographic analysis methods. The method was linear over the concentration range of 0.34-34000 pg/mL (r = 0.9985) with a limit of detection 8.0 x 10(-4) nM. The method has the requisite accuracy, sensitivity, precision, and selectivity to assay naltrexone in tablets. The influences of pH of eluent, accumulation potential, sweep rate, and accumulation time on the determination of the naltrexone were considered. PMID- 17286294 TI - Use of chitosan-alginate as alternative pelletization aid to microcrystalline cellulose in extrusion/spheronization. AB - Two types of different molecular weight chitosan were investigated as a pelletization aid in extrusion/spheronization using water as granulation liquid. Spherical pellets with a maximum fraction of 60% w/w chitosan could be produced when 1.25-2.5% w/w sodium alginate was included in the formulations with no microcrystalline cellulose (MCC). Chitosan with lower molecular weight of 190 kDa showed a better pellet forming property. The pellets obtained had acceptable physical characteristics and a fast drug release. The results from Fourier transform infrared spectroscopy, differential scanning calorimetry and (13)C CP MAS nuclear magnetic resonance spectroscopy confirmed the formation of polyelectrolyte complex (PEC) between chitosan and sodium alginate, which might be a reason for successful pelletization by extrusion/spheronization. Moreover, the presence of PEC might influence the physical characteristics and dissolution behavior of chitosan-alginate pellets. The results indicated an achievement in production of pellets by extrusion/spheronization without using MCC. Moreover, chitosan combined with sodium alginate could be used as a promising alternative pelletization aid to MCC in extrusion/spheronization. PMID- 17286295 TI - Transseptal puncture: use of an angioplasty guidewire for enhanced safety. AB - During transseptal puncture, once the needle tip has successfully accessed the left atrium, advancement of the needle, dilator and sheath into the left atrium can risk left atrial free wall perforation, particularly if the interatrial septum is aneurysmal and tents far into the left atrial cavity during puncture. We have modified our transseptal technique such that once the left atrium is accessed with the needle tip, a 0.014'' angioplasty guidewire is advanced down the Brockenbrough needle. This is guided into the left upper pulmonary vein, and the needle, dilator and sheath advanced over this wire towards the left upper pulmonary vein. In this way, the risk of perforation of the left atrial free wall is negated. We have since used this technique in 30 cases without difficulties. PMID- 17286296 TI - Successful coronary intervention after percutaneous aortic valve replacement. AB - Percutaneous aortic valve replacement has been reported previously. Progression of underlying coronary artery disease is expected with the aging population. We report the case of an 85 year old patient who underwent successful percutaneous coronary stent placement 15 months after receiving an Edwards percutaneous heart valve in the aortic position. Coronary angiography, stent deployment, and crossing of the aortic valve were all completed without any complications using standard angiographic catheters. PMID- 17286297 TI - Evaluation of the General Practice Research Database congenital heart defects prevalence: comparison to United Kingdom national systems. AB - BACKGROUND: As part of an effort to validate the General Practice Research Database (GPRD) for future studies of medication use in pregnancy, this study examined whether the rates of all, and specific types of, congenital heart defects obtained from the GPRD are similar to those obtained from UK national systems. METHODS: The prevalence rates of heart defects for 2001-2003 were determined from the GPRD and compared with both the National Congenital Anomaly System (NCAS) and the European Concerted Action of Congenital Anomalies and Twins (EUROCAT). Rate ratios (RRs) and 95% CIs were calculated comparing the prevalence of all congenital heart defects as well as specific types of heart defects in the three data sources. In addition, the effect of the child's age on the frequency of heart defects in the GPRD was determined. RESULTS: The prevalence of heart defects in the GPRD was more than twice as high as in the NCAS and slightly higher than in the EUROCAT. All differences were statistically significant. The prevalence of specific heart defects varied across the GPRD, NCAS, and EUROCAT. The measured prevalence of congenital heart defects in the GPRD was higher if calculated including children up to age 6. CONCLUSIONS: The comparisons of the GPRD prevalence rates to national prevalence estimates demonstrate that the GPRD can serve as a more complete source of background prevalence for the most commonly occurring congenital heart defects, which is essential to properly assess possible associations between maternal exposures and congenital heart defects. PMID- 17286299 TI - DNA adducts in human placenta exposed to ambient environment and passive cigarette smoke during pregnancy. AB - BACKGROUND: The risk of human diseases and abnormal development under the relatively reduced toxic environmental exposure conditions of passive cigarette smoke and urban pollution is emerging as significant. To assess the genotoxic potential of such exposure, we analyzed the DNA adducts of polynuclear aromatic hydrocarbons (PAH), a proven marker of genotoxicity, in human placental DNA samples of pregnancies monitored for passive cigarette smoke exposure. METHODS: Maternal exposure to active and passive cigarette smoke was evaluated by verbal disclosure and urinary nicotine and cotinine measurements. PAH-DNA adducts were assayed by ELISA using a polyclonal antibody against benzo[alpha]pyrene-diol epoxide-DNA in placental DNA. Birth weights of infants were recorded in these monitored pregnancies. RESULTS: Urinary nicotine and cotinine values were reduced in the passive smoke-exposed group compared to smokers and similar to those in the nonsmoker ambient exposure group. PAH-DNA and nicotine/cotinine values were not correlated with birth weight of the infant. PAH-DNA adducts were present in approximately 25% of samples exposed to passive cigarette smoke and ambient environment. CONCLUSIONS: The study has revealed that a subpopulation of humans is predisposed to accumulating PAH adducts independent of high levels of PAH sources (e.g., maternal cigarette smoke exposure). Because DNA adducts promote genomic changes, it is likely that this subpopulation is susceptible to diverse changes in the genome that may influence human development. PMID- 17286298 TI - Cardiovascular abnormalities in Folr1 knockout mice and folate rescue. AB - BACKGROUND: Periconceptional folic acid supplementation is widely believed to aid in the prevention of neural tube defects (NTDs), orofacial clefts, and congenital heart defects. Folate-binding proteins or receptors serve to bind folic acid and 5-methyltetrahydrofolate, representing one of the two major mechanisms of cellular folate uptake. METHODS: We herein describe abnormal cardiovascular development in mouse fetuses lacking a functional folate-binding protein gene (Folr1). We also performed a dose-response study with folinic acid and determined the impact of maternal folate supplementation on Folr1 nullizygous cardiac development. RESULTS: Partially rescued preterm Folr1(-/-) (formerly referred to as Folbp1) fetuses were found to have outflow tract defects, aortic arch artery abnormalities, and isolated dextracardia. Maternal supplementation with folinic acid rescued the embryonic lethality and the observed cardiovascular phenotypes in a dose-dependant manner. Maternal genotype exhibited significant impact on the rescue efficiency, suggesting an important role of in utero folate status in embryonic development. Abnormal heart looping was observed during early development of Folr1(-/-) embryos partially rescued by maternal folinic acid supplementation. Migration pattern of cardiac neural crest cells, genetic signals in pharyngeal arches, and the secondary heart field were also found to be affected in the mutant embryos. CONCLUSIONS: Our observations suggest that the beneficial effect of folic acid for congenital heart defects might be mediated via its impact on neural crest cells and by gene regulation of signaling pathways involved in the development of the pharyngeal arches and the secondary heart field. PMID- 17286300 TI - In memoriam. Robert Warwick Miller. PMID- 17286301 TI - Acyclovir delivery matrices based on poly(ethylene glycol)/chitosan semi interpenetrating networks. AB - Chitosan matrix systems have been studied as potential vehicles for the prolonged release of acyclovir (ACV). The influence of chitosan concentration (from 0.83% to 1.67%) on viscoelastic properties of formulations with and without glyoxal was analyzed. For chitosan-poly(ethylene glycol) 400 formulations loss modulus (G'') are greater than storage modulus (G'). This corresponds to the characteristic behavior of nonstructured systems. When glyoxal was added to the chitosan poly(ethylene glycol) 400 formulations, gelled matrix was obtained (i.e., G' is higher than G''), except for the lowest chitosan concentration. ACV release rates for the both types of systems, with and without glyoxal, were also determined. The ACV diffusion coefficient values from matrices are less than for the respective formulation without glyoxal and it was found to depend on the crosslink density within the matrices. Viscoelastic parameters, dynamic moduli (G', G''), and complex viscosity (eta*), were correlated with the ACV diffusion coefficients (D). The complex viscosity (eta*) could be used as a parameter of predictive value for the release rate of drugs. PMID- 17286302 TI - Maternal plasma pyridoxal-5'-phosphate concentrations and risk of isolated oral clefts in the Philippines. AB - BACKGROUND: We report that inadequate vitamin B-6 status of Filipino mothers, assessed by erythrocyte aspartate aminotransferase activity coefficient (EAST AC), is associated with an increased risk for isolated cleft lip with or without cleft palate (CL/P) in their children. Its association with the status assessed by plasma pyridoxal-5'-phosphate (PLP) concentrations is unknown. METHODS: In a case-control study in the Philippines including 46 cases (mothers of a child with CL/P) and 392 controls (mothers of an unaffected child), we evaluated the association between the risk for CL/P and maternal vitamin B-6 status assessed by PLP and EAST-AC. RESULTS: The ORs of CL/P were estimated by classifying mothers by PLP (>30, 20-30, and <20 nmol/L). Using the highest PLP group as the reference, ORs (95% CIs) were 1.03 (0.45-2.37) and 2.66 (1.30-5.50) for the middle and lowest groups, respectively (p trend = .01). In multivariate models controlling for various covariates including folate, the risk for CL/P was approximately 12 times higher in mothers with inadequate vitamin B-6 status, assessed by both PLP and EAST-AC values, compared to those with adequate status by both values. CONCLUSIONS: Inadequate vitamin B-6 status assessed by maternal PLP and EAST-AC values independently and both combined was associated with an increased risk for CL/P. The association was highest when both values were considered, suggesting that the measurement of both PLP and EAST-AC provides better assessment of vitamin B-6 status than either measurement alone. PMID- 17286303 TI - Inadequacy of fluconazole dosing in patients with candidemia based on Infectious Diseases Society of America (IDSA) guidelines. AB - INTRODUCTION: Based on Infectious Diseases Society of America (IDSA) guidelines, inappropriate fluconazole therapy in patients with candidemia is defined as an empiric dose <6 mg/kg/d, <12 mg/kg/d after Candida glabrata identification, or continued fluconazole use after identification of Candida krusei. However, the extent to which inappropriate antifungal therapy is due to improper dosing or drug selection has not been well investigated. The objectives of this study were to assess the incidence of inappropriate fluconazole therapy in patients with candidemia and to identify variables associated with inappropriate therapy. METHODS: Retrospective cohort study from four medical centers of hospitalized patients with candidemia prescribed fluconazole. Appropriateness of fluconazole dosages (adjusted for renal dysfunction) was assessed at the time of symptom onset and after Candida identification. RESULTS: Patients (206) were identified. Sixty-one of 112 (55%) patients who were given empiric therapy received an initial dose of fluconazole <6 mg/kg. After identification of the Candida species, 97 of 206 (47%) patients received inadequate fluconazole therapy based on IDSA guideline recommendations due to a fluconazole dose <12 mg/kg after isolation of C. glabrata (12%), continued use of fluconazole after isolation of C. krusei (3%), or a dose <6 mg/kg for all other Candida species (32%). Using multivariate logistic regression, increased weight in 1-kg increments (OR: 1.02; p = 0.0142) and a creatinine clearance (CRCL) >50 ml/minute (OR: 3.17; p = 0.0003) were associated with increased risk of inadequate fluconazole therapy. CONCLUSION: A high prevalence of suboptimal dosing of fluconazole given empirically or after Candida species identification was documented. Increased weight and CRCL were significant predictors of inadequate fluconazole doses. PMID- 17286304 TI - Trends in psychotropic medication use among U.S. adults. AB - PURPOSE: To examine trends and prevalence of prescription psychotropic medication use among noninstitutionalized US adults. METHODS: Prescription medication data from the third National Health and Nutrition Examination Survey (NHANES; 1988 1994; n = 20 050) and the 1999-2002 NHANES (n = 12 060), two nationally representative cross-sectional health examination surveys, were examined for persons aged > or =17 years. RESULTS: The age-adjusted prevalence of psychotropic medication use increased from 6.1% in 1988-1994 to 11.1% in 1999-2002 (p < 0.001). This was due to more than a three-fold increase in antidepressant use (2.5%, 1988-1994 vs. 8.1%, 1999-2002 (p < 0.001)). Significant increases between time periods for antidepressant use were seen for all age, gender, and race ethnic groups although increases were less pronounced for males than females and non-Hispanic blacks and Mexican Americans than non-Hispanic whites. Prevalence of use remained relatively constant from 1988-1994 to 1999-2002 for anxiolytic/sedative/hypnotic (ASH) medications (3.5-3.8%), antipsychotics (0.8 1.0%), and antimanic agents (0.3-0.4%). The age-adjusted prevalence of multiple psychotropic medication use increased from 1.2% in 1988-1994 to 3.1% in 1999-2002 (p < 0.001). CONCLUSIONS: Psychotropic medication use among US adults increased since 1988-1994, specifically of antidepressants. Increases varied by gender and race-ethnicity indicating under-utilization for non-Hispanic blacks and Mexican Americans compared to non-Hispanic whites for both males and females. PMID- 17286305 TI - Complete discrepancy between QF-PCR analysis of uncultured villi and karyotyping of cultured cells in the prenatal diagnosis of trisomy 21 in three CVS. AB - OBJECTIVE: To investigate complete discrepancies in the prenatal diagnosis of trisomy 21 between QF-PCR analysis of uncultured villi and karyotyping of cultured cells in three chorion villus samples. METHODS: Clinical details were obtained from all three patients. Follow-up studies were undertaken where possible by evaluation of chromosome 21 copy number with QF-PCR, interphase FISH, MLPA and karyotyping, and by post-mortem examination. RESULTS: Case 1: severe oligohydramnios and microcephaly on scan. QF-PCR: trisomy 21; MLPA: trisomy 21; cultured karyotype: 46,XY[48]. Placental and fetal tissue results and post-mortem examination indicated a euploid fetus with trisomy 21 mosaicism confined to the placenta. Case 2: Down screen risk 1:16; NT = 4.4 mm; absent nasal bone (Caucasian mother). QF-PCR: disomy 21; cultured karyotype: 47,XY,+ 21[23]. Neck thickening noted at delivery-post-mortem refused, no fetal tissue available. Placental tissue indicated mosaicism for trisomy 21. Case 3: Down screen risk 1:91; NT = 6.7 mm. QF-PCR: disomy 21; cultured karyotype: 46,XX,der(21;21)(q10;q10)[60]. No follow-up possible. PCR genotyping of cultured cells confirmed sample identity in all three cases. Chromosome 21 markers observed by PCR were biallelic in all three cases, indicating that a mitotic error could account for the presence of the abnormal cell lines in each case. CONCLUSION: QF-PCR analysis of uncultured villi and cultured karyotyping may rarely show complete discrepancy in the prediction of fetal trisomy 21 in CVS. Within-biopsy sample mosaicism, together with the testing of different cell populations, provide an explanation for these results. Practical ways to minimise the risk of such discrepancy are proposed. PMID- 17286306 TI - An epidemiological study of holoprosencephaly from a regional congenital anomaly register: 1995-2004. AB - BACKGROUND: Adequate contemporary information to counsel patients with a prenatal diagnosis of holoprosencephaly is lacking. We addressed this using data from the West Midlands Congenital Anomaly Register (WMCAR), a population-based malformation register, during a time where technological improvements have been stable and anomaly screening is well established. METHODS: Cases were defined using the ICD 10 code for holoprosencephaly. Cases of livebirths, stillbirths and termination at all gestations were included in the study. The diagnosis was verified by a pathology or definitive radiological report with cross validation from the regional pathology, clinical genetics, cytogenetics and fetal medicine databases. RESULTS: There were 113 cases reported of holoprosencephaly for the years 1995-2004. This represents a prevalence of 1.7 per 10,000 births and terminations, with no change in prevalence over time. There was a decreased risk of holoprosencephaly in the white population [white vs. nonwhite; RR 0.53(0.36 0.79)]. Karyotypical abnormality was noted in 46% of cases where the karyotype was known. Trisomy 13 was the most common chromosomal abnormality. Correct allocation of a diagnosis of holoprosencephaly by ultrasound occurred in 77% of cases, with another 12% having a severe intracranial abnormality but was not reported as holoprosencephaly. In 4%, a prenatal diagnosis of holoprosencephaly was not made. Termination of pregnancy was performed in 80% of all cases. CONCLUSION: Holoprosencephaly is a morbid condition associated with significant secondary etiologies. PMID- 17286307 TI - Secondary infertility as a late complication of vesico-amniotic shunt therapy. AB - OBJECTIVE: Vesico-amniotic shunting can be used for the treatment of fetal obstructive uropathy. However, the procedure is associated with a significant risk of complications. We report a case of a complicated vesico-amniotic placement, where a vesico-amniotic shunt ultimately resulted in, fortunately reversible, infertility. CASE: A 36-year-old multigravida was referred to our center at 13 weeks' gestation for the evaluation of fetal lower urinary obstruction. A vesico-amniotic shunt placement requiring several attempts was performed. A few weeks later premature rupture of the membranes occurred. At the request of the parents, the pregnancy was terminated at 22 weeks'gestation. The patient visited us again for secondary infertility, which turned out to be caused by a shunt left behind in the uterus, acting as an IUD. After hysteroscopic removal, she soon became pregnant again. CONCLUSION: This case illustrates the importance of careful documentation relating to each and every operation, of all materials used and what was retained in the patient. At delivery, obstetric staff should be completely aware of the prenatal treatment procedures performed, to ensure that no foreign objects are left by oversight, inside the patient's body. PMID- 17286308 TI - Major fetal abnormalities associated with positive screening tests for Smith Lemli-Opitz syndrome (SLOS). AB - OBJECTIVE: Determine the relationship between positive screening interpretations for Smith-Lemli-Opitz syndrome (SLOS) and other fetal abnormalities, to aid counseling and diagnostic activities. METHODS: An SLOS screening algorithm was incorporated into California's second-trimester screening program for Down syndrome and open neural tube defects (ONTDs). Between 2002 and 2004, 777 088 pregnant women were given an SLOS risk interpretation, using alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotrophin (hCG) measurements. Outcomes were obtained in 98.8% of screen-positive pregnancies. RESULTS: SLOS screen positives, alone or in combination with screen positives for other fetal disorders (Down syndrome, trisomy 18, ONTD), were associated with a high risk for fetal pathology. Type and frequency of chromosomal or anatomic abnormalities (or fetal death) varied according to screen-positive combination. Among 2018 screen-positive pregnancies, 644 fetal deaths were identified. Among the 1374 viable pregnancies, 519 were screen positive for SLOS alone; two SLOS cases and 51 other serious abnormalities were identified (14 aneuploidies; 37 anatomic). The remaining 855 were also screen positive for at least one other disorder; two SLOS cases and 327 other abnormalities were identified (180 aneuploidies; 157 anatomic). CONCLUSION: For screening programs implementing the SLOS algorithm, the present data may be useful for counseling and to guide diagnostic studies. PMID- 17286309 TI - External quality assessment of rapid prenatal detection of numerical chromosomal aberrations using molecular genetic techniques: 3 years experience. AB - OBJECTIVES: Prenatal diagnosis using rapid molecular genetic techniques is now a widely used method for detecting the most prevalent chromosomal aneuploidies. The object of this work was to develop a methodology for delivering external quality assessment (EQA) appropriate to the needs of routine diagnostic testing laboratories. METHODS: We have provided three rounds of EQA using 15 different samples over 3 years. The scheme has developed to assess both the genotyping accuracy of the results and the appropriateness of the clinical reports issued to the referring clinician. RESULTS: Participation in the EQA scheme has increased from 9 to 27 laboratories from across Europe over the three sample distributions. All laboratories have used quantitative fluorescence-PCR (QF-PCR) to analyse these samples except for a sole participant in 2006 who used multiplex ligation dependent probe amplification (MLPA). In total 265 samples have been distributed, of which four (1.5%) were not reported due to technical failures and one (0.4%) was reported incorrectly and must be regarded as a genotyping error. CONCLUSIONS: We have demonstrated a significant and increasing demand for EQA in the rapid detection of aneuploidies in UK and other European laboratories. Using the methodologies described, we have had a very low rate of technical failures and demonstrated a high level of genotyping accuracy. However, the quality of the clinical reports was variable and suggestions are made for improvement. PMID- 17286310 TI - Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast. AB - OBJECTIVE: To test the hypothesis that free fetal DNA (ffDNA) circulating in maternal plasma originates mainly from the placenta we studied ffDNA levels in anembryonic pregnancies. METHODS: Maternal blood samples were collected from 15 normal first-trimester pregnancies in which fetal sex was subsequently determined and nine patients with a diagnosis of anembryonic gestation (AG). The Y chromosome DYS14 gene was quantified by real-time quantitative PCR (RT-PCR) for the determination of fetal sex in both plasma and chorionic tissue samples. Fetal sex in chorionic tissue samples was also determined using quantitative fluorescence PCR (QF-PCR). RESULTS: The correct sex result was obtained from maternal plasma in all. Four AG pregnancies were female (DYS14 negative) results. In five of the AG cases, the chorionic tissue was found to be male (by both QF PCR and RT-PCR which agreed) and positive male signal was found in maternal plasma by RT-PCR. There was no statistical difference between median free fetal DNA concentration in plasma between the AG male cases (148.3 GE/mL) and controls (145.8 GE/mL). CONCLUSION: Since ffDNA levels are normal in pregnancies without a fetus, the data support the hypothesis that the trophoblastic cells are the major source ffDNA in maternal plasma. PMID- 17286311 TI - Does vaginal bleeding influence first-trimester markers for Down syndrome? AB - OBJECTIVES: To examine the effect of early vaginal bleeding on first-trimester screening markers for Down syndrome. METHODS: A retrospective study was conducted on 1755 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome on the basis of ultrasound and maternal serum markers. Fetal delta-nuchal translucency (NT), maternal serum pregnancy associated plasma protein A (PAPP-A) and free beta-hCG were compared between pregnancies with (n = 252) and without (n = 1503) an episode of vaginal bleeding. Subgroup analysis for the intensity of bleeding (spotting n = 191; light n = 32; heavy n = 29) was performed. RESULTS: The median +/- SD (log(10)) for delta-NT, multiple of medians (MoM) PAPP-A and MoM free beta-hCG (corrected for maternal weight, smoking and ethnicity) was - 0.17 +/- 0.62, 1.10 +/- 0.28, 1.1 +/- 0.28 and - 0.15 +/- 0.51, 0.98 +/- 0.26, 0.94 +/- 0.3 in pregnancies with and without a history of early vaginal bleeding, which were not significantly different. Exclusion of patients with spotting from the vaginal bleeding group revealed significantly higher maternal serum free beta-hCG MoM values (median +/- SD (log(10))) compared to patients without bleeding, 1.29 +/- 0.27 vs 0.96 +/- 0.3(p = 0.011). Screen-positive (cut off of 1:350) rate after combined first-trimester screening was 28.1% in patients with light vaginal bleeding and 8.4% in patients without bleeding (p = 0.001). CONCLUSIONS: Light vaginal bleeding before first trimester combined screening for Down syndrome leads to a higher screen-positive rate after combined first trimester screening, without a significant difference in serum levels of the screening markers. PMID- 17286312 TI - Advantages of multiple markers and polar body analysis in preimplantation genetic diagnosis for Alagille disease. AB - OBJECTIVE: The development of a preimplantation genetic diagnosis (PGD) protocol for Alagille syndrome (AGS), a rare autosomal dominant disorder with hepatic, cardiac and ophthalmologic involvement. METHODS: We developed a polar body (PB) based multiplex fluorescent PCR reaction for a female affected with AGS. The protocol included analysis of the Jagged 1 (JAG1) familial mutation and five closely linked highly polymorphic markers (D20S162, D20S901, D20S894, and D20S186). RESULTS: In two cycles of PGD 9 of ten embryos were accurately diagnosed by assessment of first and second PBs, one embryo required additional blastomere biopsy. CONCLUSIONS: This protocol takes advantage of the larger window of opportunity for transfer and the increased accuracy of diagnosis afforded by the combination of PB biopsy and multiple marker analysis. Two cycles resulted in the transfer of two and three mutation-free embryos and a subsequent pregnancy as measured by the rising hCG levels. PMID- 17286313 TI - Single umbilical artery and its siding in the second trimester of pregnancy: relation to chromosomal defects. AB - OBJECTIVES: To determine the possible association between single umbilical artery (SUA) in the second trimester of pregnancy and the incidence of chromosomal abnormalities. To determine whether the presence of chromosomal defects in fetuses with SUA is related to the side of the missing artery. METHODS: Color flow imaging of the fetal pelvis was used to determine the number of umbilical arteries in 2147 fetuses immediately before amniocentesis for karyotyping in the second trimester of pregnancy. RESULTS: SUA was diagnosed in 102/2147 (4.8%) cases. The left umbilical artery was absent in 60/102 (58.8%) fetuses, compared with the 42/102 (41.2%) for the right artery. The rate of chromosome abnormalities was significantly higher among fetuses with SUA than among those with 2 umbilical arteries (19/102 or 18.6% versus 109/2045 or 5.3%; OR = 4.1, 95% CI 2.3-7.1, p < 0.0001). Among fetuses with SUA, there was no significant difference in the rate of chromosome abnormalities between those with absence of the left versus the right artery (11/60 or 18.3% versus 8/42 or 19.0%, p = 0.93). There was an SUA in 5/39 (12.8%) cases with trisomy 21, 8/16 (50%) with trisomy 18, 1/4 (25%) with trisomy 13 and 5/69 (7.2%) with other chromosomal defects. There were no chromosome abnormalities in fetuses where a single umbilical artery was an isolated sonographic finding. All fetuses with SUA and chromosomal defects had associated abnormalities detected by ultrasound. CONCLUSION: A single umbilical artery (SUA) in the second trimester of pregnancy has a high association with trisomy 18, 13, 21 and other chromosomal defects, but all chromosomally abnormal fetuses had associated malformations detected by ultrasound. The absence of the left artery is more frequent than the absence of the right artery. The association with chromosomal abnormalities seems to be equal on each side. PMID- 17286314 TI - Two-way trafficking of Annexin V positive cells between mother and fetus: determination of apoptosis at delivery. AB - OBJECTIVES: The aim of this study was to quantitate apoptosis in maternal circulation and umbilical cord blood (UCB) at delivery. The proportion of fetal cells in maternal blood as well as that of maternal cells in UCB was also determined. MATERIAL AND METHODS: Three milliliters of peripheral blood was collected from nine women during labor. Five women delivered males and four delivered females. Immediately after delivery, 3 mL UCB was collected. Ten microliters was used to quantitate apoptosis by the ethidium bromide assay (EthBr) and from the remaining blood, Annexin V positive cells were isolated by MACS. RESULTS: The Median apoptosis rate in maternal samples was 25% (19-34) and in UCB 20% (16-28). Annexin V positive cells were present in all samples analyzed. As shown by Fluorescence in situ hybridization (FISH) in maternal samples, cells with an XY hybridization pattern were identified in cases with male newborns in a median concentration of 1.7% (1.6-2.1). On the corresponding UCB, a median of 1.2% (0.8-1.6) XX cells were detected. CONCLUSION: The study demonstrates the existence of a bidirectional transfer of fetal and maternal cells under apoptosis across the placenta and provides useful information regarding use of UCB for transplantation. PMID- 17286315 TI - Complete chorioamniotic membrane separation with fetal restrictive dermopathy in two consecutive pregnancies. AB - OBJECTIVE: To describe an instance of complete chorion-amnion membrane separation with fetal restrictive dermopathy in two consecutive pregnancies. METHODS: We performed prenatal ultrasounds in two consecutive pregnancies and evaluated gross and microscopic postnatal findings. RESULTS: The first pregnancy ended at 32 weeks of gestation with spontaneous chorioamniotic membrane separation and preterm premature rupture of membranes. The mother delivered an abnormal male infant with generalized fixed joint contractures, rigid and shiny skin, skin laceration around the neck, a rounded and opened mouth, and palpebral conjunctival eversion. The subsequent pregnancy was also complicated by spontaneous complete chorioamniotic membrane separation, oligohydramnios, and fetal growth restriction at 26 + 3 weeks of gestation. A immaturely born second baby also carried multiple anomalies similar to those of the first. Both infants died shortly after birth. After microscopic examination of the skin, we diagnosed the infant as restrictive dermopathy. CONCLUSIONS: Complete separation of the chorion-amnion membrane may be regarded as a serious prenatal condition. Restrictive dermopathy or skin disorders caused by defects in collagen or elastic tissue metabolism may be one of the many causes of chorion-amnion separation. PMID- 17286316 TI - Confined blood chimerism in monochorionic dizygous (MCDZ) twins. AB - OBJECTIVE: To present the risk factors, prenatal and postnatal implications of monochorionic dyzygotic twinning. METHODS: We present a case of monochorionic twins diagnosed on first-trimester ultrasound following a 2-embryo transfer in vitro fertilisation pregnancy. Postnatal buccal smears performed as part of a twin research study revealed the twins to be dizygous, and DNA testing on peripheral blood lymphocytes confirmed the presence of blood chimerism. RESULTS: Despite the monochorionic placentation, buccal swabs revealed discordant results for all four microsatellite loci tested, consistent with dizygosity. Zygosity testing on peripheral blood lymphocytes revealed that, of the nine DNA microsatellite loci tested, three had all four parental alleles represented. This result was concordant between the twins. The diagnosis of blood chimerism was thus confirmed, presumably due to the inter-twin vascular anastomoses of the monochorionic placenta. CONCLUSION: Monochorionic dizygous twinning is rare, but appears to be more common after assisted reproduction. It is presumed that outer cell mass fusion may occur when two embryos are replaced in close proximity. These pregnancies are not only at risk for the usual complications of monochorionicity, but also have the potential to be heterokaryotypic. Postnatally, the twins may have long-term blood chimerism. PMID- 17286317 TI - Microphthalmia with linear skin defects (MLS) syndrome evaluated by prenatal karyotyping, FISH and array comparative genomic hybridization. AB - OBJECTIVE: To explore the utility of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of microphthalmia and linear skin defects syndrome. METHODS: We used karyotype analysis, FISH and array CGH to investigate an X;Y translocation. Replication studies were done on cultured amniocytes and lymphoblasts. RESULTS: We describe a severe case of MLS syndrome that presented prenatally with multiple anomalies including cystic hygroma, microphthalmia, intrauterine growth restriction and a complex congenital heart defect. Cytogenetic analysis of amniocytes revealed an unbalanced de novo translocation between chromosomes X and Y [karyotype 46,X,der(X)t(X;Y)(p22.3;q11.2).ish der(X)(DXZ1+,DMD+,KAL-,STS-,SRY-),22q11.2 (Tuple1 x 2)]. MLS diagnosis was made at birth and the prenatal karyotype was confirmed. Replication studies showed the derivative X chromosome was the inactive X. Array CGH confirmed the X and Y imbalances seen in the karyotype and also showed twelve BACs in the MLS region were deleted as a result of the translocation. FISH with BAC clones verified the array findings and placed the X breakpoint in Xp22.2, resulting in the amended karyotype, 46,X,der(X)t(X;Y)(p22.2;q11.2).ish der(X)(DXZ1+,DMD+,KAL-,STS-,SRY ),22q11.2(Tuple1 x 2) arr cgh Xp22.33p22.2(LLNOYCO3M15D10 -->GS1-590J6)x 1,Yq11.222q23(RP11-20H21-->RP11-79J10)x 1. CONCLUSION: The sensitivity of array CGH was valuable in detecting monosomy of the MLS critical region. Array CGH should be considered for the prenatal diagnosis of this syndrome. PMID- 17286318 TI - Reasons for antidepressant prescriptions in Canada. AB - PURPOSE: To describe reasons reported by physicians making recommendations for treatment with antidepressant medications. METHODS: Data collected by IMS Health Canada in a database called the Canadian Disease and Therapeutic Index (CDTI) were used in this analysis. CDTI data are collected from a representative sample of office-based physicians who complete diaries in their practices during selected sampling periods. A drug recommendation is recorded each time a treatment is recommended. The data are weighted to produce national estimates of the frequency of such recommendations. RESULTS: The frequency of recommendations for antidepressant treatment increased between 2000 and 2004. However, there was a slight decrease in 2005. Two types of antidepressant medications, tricyclic antidepressants (TCAs) and trazodone showed distinct patterns of use. TCAs were more commonly used for non-psychiatric indications than for psychiatric indications, especially for sleep- and pain-related reasons. Trazodone was frequently recommended for sleep problems. The proportion of recommendations for depressive disorders for antidepressants as a group remained stable over the 5 year study period. CONCLUSIONS: About one-third of antidepressant recommendations are for reasons other than depression. It can no longer be assumed that the frequency of antidepressant use is a measure of the frequency of pharmacological depression treatment. However, prescription data may be useful for tracking trends. PMID- 17286319 TI - Statins and fracture risk. A systematic review. AB - PURPOSE: To summarize current evidence on statin use and fracture risk and to explore potential sources of heterogeneity among study results. METHODS: A computerized search was conducted on MEDLINE, EMBASE, and the Cochrane databases using the keywords HMG-CoA reductase inhibitor, osteoporosis, and fractures. A meta-analysis was performed to summarize results of studies identified. RESULTS: Statin use was associated with a 23% lower fracture risk (OR = 0.77, 95%CI: 0.66 0.90). An effect of statins was found in case-control (OR = 0.62, 0.45-0.85, n = 6) and cohort (OR = 0.77, 0.59-1.00, n = 8) studies, but not in post hoc analyses of randomized trials (OR = 1.03, 0.91-1.16, n = 4). A reduced risk with statin use was found for fractures of the hip (OR = 0.58, 0.46-0.74, n = 16), spine (OR = 0.65, 0.48-0.88, n = 8) and other sites (OR = 0.77, 0.60-1.00, n = 7), and both in women (OR = 0.80, 0.66-0.96, n = 11) and men (OR = 0.62, 0.36-1.08, n = 3). Among the observational studies that also evaluated the effect of other lipid lowering drugs, no reduced fracture risk was found for these agents (OR = 0.96, 0.85-1.09, n = 10). The test for heterogeneity was significant for study results of statin use versus no-use (p < 0.01). Meta-regression analyses suggested that study design might partly account for the heterogeneity. There was an indication of publication bias by examining Begg's plot, although Egger's test was not significant (p = 0.13). CONCLUSIONS: Current evidence does not support an effect of statins in preventing fractures given (i) the lack of association in randomized trials, (ii) the heterogeneity among observational studies, (iii) the potential residual confounding, and (iv) the potential publication bias. PMID- 17286320 TI - Vaccines and changes in coagulation parameters in adults on chronic warfarin therapy: a cohort study. AB - PURPOSE: Warfarin is commonly used among patients who receive influenza, pneumococcal, and tetanus and diphtheria toxoid vaccines, and persons on warfarin therapy may also receive Hepatitis A vaccine. There has been concern that vaccinations could potentially alter coagulation parameters in patients on warfarin therapy. We sought to determine whether vaccinations are associated with changes in International Normalized Ratio (INR) in persons on long-term warfarin therapy. METHODS: We conducted a retrospective cohort study of 5167 members of Group Health, a health maintenance organization (HMO) in western Washington State, who were aged 18 years and older and who were on stable long-term warfarin therapy between 1 January 1992 and 31 December 2003. We made within-person comparisons between mean INR values in the 28 days after receipt of influenza, pneumococcal, tetanus, or hepatitis A vaccine versus mean INR values during other times. RESULTS: Receipt of influenza vaccine was not associated with a change in INR value (mean change, 0.01; 95% confidence interval (CI) -0.01 to 0.03); similar results were observed for pneumococcal (mean change 0.01; 95%CI -0.07 to 0.09), tetanus (mean change 0.03; 95%CI -0.03 to 0.10), and hepatitis A vaccines (mean change 0.03; 95%CI -0.10 to 0.14). CONCLUSIONS: Our results do not suggest that vaccinations lead to clinically significant alterations in coagulation measures among adults on chronic warfarin therapy. PMID- 17286321 TI - Clinical interest: a study of the influence on general practitioners' prescribing. AB - PURPOSE: To analyse the association between general practitioners' clinical interest and prescribing rates in four clinical areas: dyspepsia, depression, headache and diabetes. METHODS: Data concerning general practitioners' prescribing during 2004 were retrieved from a pharmacy database and linked with data from a physician questionnaire and the National Health Insurance Register. To counterbalance differences in practice populations all 1-year prevalences of prescribing were standardised according to age and gender. Participants were asked 'To what extent do you find the following areas interesting from a professional point-of- view?' Four rating categories were used. The association between clinical interest and standardised prescribing rates was investigated using logistic regression, the Kruskal-Wallis test and a trend test. RESULTS: A total of 68 (72%) single-handed general practitioners representative of the total group completed the questionnaire. We observed a two-fold ratio between the 90% and the 10% percentiles of the 1-year prevalences of antisecretory drugs, antidepressants, migraine drugs as well as anti-diabetics. The variation in prescribing of antidepressant and antisecretory drugs was far above chance level. No significant association with clinical interest could, however, be observed for any of the four clinical areas. CONCLUSION: General practitioners' prescribing of the four classes of medical drugs varied considerably. However, only part of this variation was based on chance. This study did not confirm our hypothesis that general practitioners' level of clinical interest in one area corresponds with their prescribing of drugs used within that area. PMID- 17286322 TI - Two cases of homozygous alpha0-thalassemia diagnosed prenatally in pregnancies at risk for beta-thalassemia in China. PMID- 17286323 TI - Spin-correlated radical pairs in synthetic hairpin DNA. PMID- 17286324 TI - Ultrathin pi-conjugated polymer films for simple fabrication of large-area molecular junctions. PMID- 17286325 TI - 2D infrared chemical exchange spectroscopy of ultrafast isomerizations. PMID- 17286326 TI - Interpenetrating polar and nonpolar sublattices in intermetallics: the NaCd(2) structure. AB - In the 1960s, Samson solved the structures of some of the most complicated intermetallic phases known, including those of NaCd(2), Mg(2)Al(3), and Cu(3)Cd(4) (each with over 1000 atoms per unit cell). Following remarkable earlier constructions by Samson and by Andersson, we use quantum-mechanical calculations as a guide to describing and understanding these structures. Our electronic Aufbau begins with the relatively simple Mg(17)Al(12) structure and works up to Samson's NaCd(2) structure. In both structures, a division of the sites into electron-rich and electron-poor (with respect to an average electron count) reveals MgCu(2)-type fragments. Between the interiors and exteriors of these fragments, a change in bonding character takes place-the interiors are more polar, the interfaces relatively nonpolar. This electronic situation is traced to the geometry of the interface sites; they lie simultaneously on electron-rich and electron-poor networks. The resulting polar and nonpolar sites in NaCd(2) are separated by a minimal surface, the D surface. The driving force for assuming this structure is electronic: NaCd(2) features an interpenetration of polar and nonpolar bonding regions. This sort of thinking can be applied to other structures. PMID- 17286327 TI - Inhibition of siRNA binding to a p19 viral suppressor of RNA silencing by cysteine alkylation. PMID- 17286328 TI - Low-basicity oxygen atoms: a key in the search for propylene epoxidation catalysts. PMID- 17286329 TI - A novel reaction of the "Huisgen zwitterion" with chalcones and dienones: an efficient strategy for the synthesis of pyrazoline and pyrazolopyridazine derivatives. PMID- 17286330 TI - Bioinspired design of nanocages by self-assembling triskelion peptide elements. PMID- 17286331 TI - Arene-sandwiched silver(I) pyrazolates. PMID- 17286332 TI - Enantioselective organocatalytic conjugate addition of N heterocycles to alpha,beta-unsaturated aldehydes. PMID- 17286333 TI - A gadolinium triacetic monoamide DOTA derivative with a methanethiosulfonate anchor group. Relaxivity properties and conjugation with albumin and thiolated particles. AB - The gadolinium(III) complex with a new DOTA-based ligand bearing a methanethiosulfonate group (MTS) was synthesized and its relaxivity properties were investigated. MTS-ADO3A is a triacid DOTA derivative with an amide arm substituted by an ethylmethanethiosulfonate function. This ligand was obtained in two steps: tri-tert-butyl 2,2',2''-(1,4,7,10-tetraazacyclododecane-1,4,7 triyl)triacetate was reacted with S-(2-aminoethyl)methanesulfonothioate and the tert-butyl groups were removed with trifluoroacetic acid. The Gd(III) MTS-ADO3A complex readily formed disulfide bonds with albumin (BSA) in its native and reduced forms and with thiolated silica particles. Four- to five-fold relaxivity increases at 20 MHz were measured on the isolated adducts. The EuMTS-ADO3A chelate was found to be monohydrated by fluorescence and the relaxivity parameters of the Gd(III) complex were obtained by (17)O NMR and by measuring the nuclear magnetic relaxation dispersion between 0.01 and 80 MHz. The water exchange time tau(m) is increased upon forming disulfide bonds with macromolecules and particles and the relaxivity gains of all the complexes are limited by the tau(m) factor. Forming covalent or hydrophobic/electrostatic bonds with BSA seems to bring about similar relaxivity changes but the covalent BSA adducts can be isolated and their properties can be directly studied. The addition of dithiothreitol or glutathione leads to the removal of the metal chelates from the macromolecules, as indicated by the relaxation times reverting to their values before binding. It is thus expected that the chelate will stay in the body long enough for imaging but will still be excreted through the kidneys. PMID- 17286334 TI - Different components of opioid-substitution treatment predict outcomes of patients with and without a parent with substance-use problems. AB - OBJECTIVE: The aim of this study was to determine how the treatment needs and outcomes of polysubstance-using patients entering opioid-substitution treatment (OST) may be affected if the patient had a parent with substance-use problems. METHOD: This prospective observational study examined outcomes of 255 patients (97% male) entering OST at eight clinics in the Veterans Health Administration. Self-reported substance-use outcomes in the first year of treatment were compared between patients with (n = 121) and without (n = 134) a parent with substance-use problems. The association between receipt of practice guideline-recommended elements of care and treatment outcome was examined. RESULTS: Parent history positive patients had greater drug use at 6 months, but by 12 months they had reduced their drug use to the same extent as parent history-negative patients. Ongoing methadone (Dolophine, Methadose) maintenance was associated with improved outcomes of drug use in parent history-negative patients; however, parent history positive patients who ended methadone maintenance reduced drug use as much as those who continued treatment. The association between treatment received and outcome differed in these populations. In parent history-negative patients, reduced severity of substance use at 1 year was predicted solely by receiving methadone for a greater number of days. In parent history-positive patients, reduced severity of substance use was predicted by receiving methadone for fewer days, by greater satisfaction with and receipt of counseling services, and by lesser tendency for providers to encourage a reduction in methadone use. CONCLUSIONS: The importance of counseling and medication components of OST may differ depending on family history. For parent history-negative patients, medication maintenance may be more therapeutically necessary. PMID- 17286335 TI - Stages and sequences of initiation and regular substance use in a longitudinal cohort of black and white male adolescents. AB - OBJECTIVE: This study examined whether developmental sequences and stages of substance-use initiation and regular use differed and, if so, whether they varied for black and white adolescent males. METHOD: The analyses were based on a cohort of inner-city boys in the Pittsburgh public schools, who had been followed prospectively from ages 7 to 19 across 18 data waves (N = 412). RESULTS: Blacks were most likely to end initiation of any use and regular use with marijuana, whereas alcohol and tobacco were the most common end stage drugs for whites. Whites were also more likely than blacks to initiate and to become regular users of hard drugs. For both races, the typical developmental sequence for substance use initiation and regular use was alcohol and/or tobacco, then marijuana, and then hard drugs. However, blacks were more likely to deviate from this sequence than were whites. Participants who initiated any substance use faced a high probability of becoming a regular user of at least one substance. CONCLUSIONS: There were differences in the sequences and stages of substance-use initiation and regular use by race. Further research is needed to identify the antecedents of escalation to regular use and progression of regular use across substances and to delineate the cultural and environmental factors that affect substance-use progression. PMID- 17286336 TI - Effects of alcohol on intraovarian nitric oxide synthase and steroidogenic acute regulatory protein in the prepubertal female rhesus monkey. AB - OBJECTIVE: In addition to affecting hypothalamic-pituitary function, alcohol is a gonadal toxin capable of inhibiting ovarian function and suppressing circulating levels of estradiol (E2) in female rats, rhesus monkeys, and adolescent girls. Both nitric oxide (NO) and steroidogenic acute regulatory protein (StAR) are intraovarian substances that influence steroidogenesis in opposite directions. This study was undertaken to determine whether alcohol exposure affects prepubertal ovarian steroidogenesis in female rhesus monkeys by altering nitric oxide synthase (NOS), StAR, or both. METHOD: At 20 months of age, monkeys received a single intragastric dose of alcohol (2.4 g/kg) or an equal volume of a saline/sucrose solution daily until they were 36 months old. Blood and ovaries were then collected for assessment of serum hormone levels and tissue gene and protein expression. RESULTS: Alcohol caused depressed levels of serum E2 (p < .05) and luteinizing hormone (p < .05) but not follicle-stimulating hormone. Real time polymerase chain reaction (RT-PCR) assessment of ovarian mRNA encoding the three isoforms (i.e., neuronal [n] NOS, endothelial [e] NOS, and inducible [i] NOS) of NOS revealed that alcohol exposure did not alter gene expression of nNOS but caused increased basal levels of eNOS (p < .05) and iNOS (p < .01) mRNA expression compared with control ovaries. Alcohol also increased expression of eNOS (p < .01) and iNOS (p < .05) proteins. In contrast, ovaries from monkeys exposed to alcohol showed decreased (p < .05) StAR gene expression compared with controls. CONCLUSIONS: We showed previously that alcohol exposure during adolescence suppressed E2 and delayed development of regular monthly menstruation patterns in rhesus monkeys. The present results suggest that the combined action of alcohol to elevate ovarian NOS and suppress StAR synthesis contributes to these abnormalities. PMID- 17286337 TI - Association of ALDH1 promoter polymorphisms with alcohol-related phenotypes in Trinidad and Tobago. AB - OBJECTIVE: Two polymorphisms in the promoter region of the gene encoding cytosolic aldehyde dehydrogenase (ALDH1A1), ALDH1A1*2 and ALDH1A1*3, have recently been identified. The present study sought to determine whether an association exists between ALDH1A1 genotypes, alcohol dependence, drinking history, and liver function tests in the two major ethnic groups of Trinidad and Tobago (TT). METHOD: The participants in this study were 137 alcohol dependents of either East Indian ancestry (Indo-TT) or African ancestry (Afro-TT) and 108 controls matched by age, gender, and ethnicity. A structured interview was used to gather information on demographics, psychiatric diagnoses, and personal drinking and drug use. A blood sample was obtained from each participant, and leukocyte DNA was extracted and used to genotype for the presence of the ALDH1A1 promoter polymorphisms. Serum levels of hepatic enzymes, as well as presence of HIV, hepatitis B surface antigen, and antihepatitis C virus antibody, were also determined. RESULTS: Twenty-four participants (10%) possessed the ALDH1A1*1/*2 genotype (frequency = .05), 4 were Afro-TT (2 alcohol dependents, 2 controls), and 20 were Indo-TT (18 alcohol dependents, 2 controls). Two participants (1 Indo TT alcohol dependent, 1 Afro-TT alcohol dependent) had the ALDH1A1*2/*2 genotype. Four participants possessed ALDH1A1*3, all of whom were Afro-TT controls. Indo-TT participants with at least one ALDH1A1*2 allele were more likely to have a lifetime diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, alcohol dependence (p < .002). Indo-TT participants with ALDH1A1*2 also reported significantly higher levels of current alcohol consumption (p < .05). The small number of Afro-TT participants with atypical polymorphisms limits any conclusions on the possible impact on alcohol dependence in that population. CONCLUSIONS: Results from this study suggest that ALDH1A1*2 may be associated with increased risk for the development of alcohol dependence in Indo-Trinidadians. PMID- 17286339 TI - Environmental policies to reduce college drinking: an update of research findings. AB - OBJECTIVE: We provide an overview of environmental strategies that may reduce college drinking. The identified environmental strategies fall into three categories: (1) reducing alcohol use and related problems among underage college students, (2) reducing risky alcohol use and related problems among all college students, and (3) de-emphasizing the role of alcohol and creating positive expectations on campus. At the time of our 2002 review, few studies had assessed environmental policies and strategies in the context of college student alcohol use and related problems. The present article summarizes recent research on the effects of environmental policies and strategies affecting college students. METHOD: We updated our previous literature searches to identify peer-reviewed research studies evaluating the effects of environmental strategies on college and general populations. RESULTS: We identified 110 new studies addressing environmental strategies published between 1999 and 2006. Thirty-six of these studies focused on the college population. The extant research indicates that many environmental strategies are promising for reducing alcohol-related problems among the general population. Several recent studies suggest that these strategies, particularly combined strategies, also may be effective in decreasing alcohol-related problems among college populations. CONCLUSIONS: Further research is needed to continue expanding our understanding of environmental strategies to identify the most effective individual and combined strategies. PMID- 17286338 TI - The Sacramento Neighborhood Alcohol Prevention Project: outcomes from a community prevention trial. AB - OBJECTIVE: This article reports the results of the Sacramento Neighborhood Alcohol Prevention Project (SNAPP). SNAPP set as its goal the reduction of alcohol access, drinking, and related problems in two low-income, predominantly ethnic minority neighborhoods, focusing on individuals between the ages 15 and 29, an age group identified with high rates of alcohol-involved problems. METHOD: Two neighborhoods in Sacramento were selected to be the intervention sites because they were economically and ethnically diverse and had high rates of crime and other drinking-related problems. The quasi-experimental design of the study took a "phased" approach to program implementation and statistical examination of outcome data. Outcome-related data were collected in the intervention sites as well as in the Sacramento community at large. Five project interventions included a mobilization component to support the overall project, a community awareness component, a responsible beverage-service component, an underage-access law enforcement component, and an intoxicated-patron law enforcement component. Archival data were collected to measure and evaluate study outcomes and to provide background and demographic information for the study. RESULTS: Overall, we found significant (p < .05) reductions in assaults as reported by police, aggregate emergency medical services (EMS) outcomes, EMS assaults, and EMS motor vehicle accidents. CONCLUSIONS: Results from the Sacramento Neighborhood Alcohol Prevention Project demonstrate the effectiveness of neighborhood-based interventions in the reduction of alcohol-related problems such as assaults, motor vehicle crashes, and sale of alcohol to minors. PMID- 17286340 TI - Correlates of in-store promotions for beer: differential effects of market and product characteristics. AB - OBJECTIVE: We estimated the strength and direction of the association between product characteristics (beer type, package size, and brand name) and market-area socioeconomic characteristics, and promoted sales of beer in grocery stores. METHOD: Supermarket scanner data from 64 market areas across the United States over 5 years were used to estimate regression models of the share of beer sales that are promoted, controlling for beer price, packaging, and type; and for market-level age, race/ethnicity, income, unemployment rate, and percentage of the population living in an alcohol control state. RESULTS: Large-volume units, such as 144-oz and 288-oz packages, are more likely to be promoted than smaller package sizes. Malt-liquor beverages are less likely to be promoted than non-malt liquor beverages. Age, race/ethnicity, income, and geographic location of the market area are not significantly related to promoted beer sales. CONCLUSIONS: Marketing research has shown that in-store merchandising and promotions can substantially increase beer sales and that purchasing large package sizes may increase total consumption. Our results suggest that high levels of promoted sales for large-volume beer packages may result in increased beer consumption. PMID- 17286342 TI - Building better cognitive-behavioral therapy: is broad-spectrum treatment more effective than motivational-enhancement therapy for alcohol-dependent patients treated with naltrexone? AB - OBJECTIVE: The current study investigated the treatment effectiveness, during treatment, of a second-generation cognitive-behavioral therapy for alcoholism- broad-spectrum treatment (BST)--compared with motivational-enhancement therapy (MET), when both were offered in conjunction with a therapeutic dose of naltrexone (Revia). METHOD: One hundred forty-nine alcohol-dependent patients completed a 3-month randomized, controlled trial of BST and naltrexone versus MET and naltrexone. RESULTS: Patients receiving BST had a significantly higher percentage of days abstinent than patients receiving MET. The superior effect of BST is particularly strong in interaction with support for drinking, suggesting that the advantage of BST is worth the additional cost for patients whose psychosocial networks are supportive of continued drinking. This effect remains significant when controlling for pretreatment percentage of days abstinent. CONCLUSIONS: In aggregate, these findings suggest that it is either the combination of naltrexone and BST or the unique properties of BST that account for BST's superiority to MET and naltrexone. The results of this initial phase of the trial suggest that a second-generation cognitive-behavioral therapy such as BST may have a meaningful clinical advantage over brief interventions such as MET, at least when combined with naltrexone. PMID- 17286341 TI - Optimizing personalized normative feedback: the use of gender-specific referents. AB - OBJECTIVE: Many brief interventions include personalized normative feedback (PNF) using gender-specific or gender-neutral referents. Several theories suggest that information pertaining to more socially proximal referents should have greater influence on one's behavior compared with more socially distal referents. The current research evaluated whether gender specificity of the normative referent employed in PNF related to intervention efficacy. METHOD: Following baseline assessment, 185 college students (45.2% women) were randomly assigned to one of three intervention conditions: gender-specific feedback, gender-neutral feedback, or assessment-only control. Immediately after completing measures of perceived norms, alcohol consumption, and gender identity, participants in the gender neutral and gender-specific intervention conditions were provided with computerized information detailing their own drinking behavior, their perceptions of student drinking, and actual student drinking. RESULTS: After a 1-month follow up, the results indicated that normative feedback was effective in changing perceived norms and reducing alcohol consumption for both intervention groups for women and men. The results provide support, however, for changes in perceived gender-specific norms as a mediator of the effects of normative feedback on reduced drinking behavior for women only. Additionally, gender-specific feedback was found to be more effective for women higher in gender identity, relative to the gender-neutral feedback. A post-assessment follow-up telephone survey administered to assess potential demand characteristics corroborated the intervention effects. CONCLUSIONS: Results extend previous research documenting efficacy of computer delivered PNF. Gender specificity and gender identity appear to be important elements to consider for PNF intervention efficacy for women. PMID- 17286344 TI - A prospective study of the effects of age of initiation of alcohol and drug use on young adult substance dependence. AB - OBJECTIVE: Previous cross-sectional research has disagreed about whether an adolescent's age of onset of alcohol use is a unique predictor of later alcohol dependence or whether it is merely a correlate of those factors that produce alcohol dependence. The current study tests this question in a longitudinal sample, and extends the literature by testing whether age of onset of alcohol and drug use predicts alcohol and drug dependence. METHOD: Data from an ongoing study of children of alcoholics and matched controls (n = 395) were collected during three annual interviews during adolescence and two 5-year follow-ups in young adulthood. RESULTS: Taking a first drink of alcohol at or before age 13 was unrelated to the odds of alcohol and drug dependence when the adolescent did not also participate in early drug use or when correlated risk factors were taken into account. On the other hand, early drug use elevated the odds of drug dependence by young adulthood, even while controlling for shared risk factors. CONCLUSIONS: The current study provides support for the notion that early adolescent onset of alcohol use is a marker of risk for later dependence rather than a causal influence. Moreover, it provides evidence for the impact of early drug use on drug-substance dependence. Implications for theory and intervention are discussed. PMID- 17286345 TI - Maternal alcohol abuse/dependence, children's behavior problems, and home environment: estimates from the National Longitudinal Survey of Youth using propensity score matching. AB - OBJECTIVE: Propensity score (PS) matching was used to investigate the relationship between maternal alcohol abuse (AA) and alcohol dependence (AD), based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria and three child outcomes: child behavior problems and two characteristics of the child's home environment as measured by the Home Observation and Measurement of the Environment-Short Form, cognitive stimulation and emotional support. METHOD: A cohort of children (N = 2,193; 49% female) whose mothers were drawn from the 1994 National Longitudinal Survey of Youth were stratified by gender and matched on maternal propensity to exhibit AA or AD. RESULTS: After matching, sons of mothers with AA/AD had higher behavior problem scores (p < or = .05), and daughters of mothers with AA/AD lived in homes with significantly less emotional support (p < or = .05) and cognitive stimulation (p < or = .005). Results were robust to alternative specifications of PS regressions. CONCLUSIONS: The findings suggest that policies aimed at reducing AA and AD among young adult women with children are justified. PS matched results also suggest that school counselors and mental health providers who encounter young boys with elevated behavior problems should consider maternal AA/AD as one possible causal factor. Future research should be directed toward understanding the trajectory of these outcomes and their sequelae over the child's life cycle and toward developing improved methods of identifying and intervening with at risk children of both genders and their mothers. PMID- 17286343 TI - Measuring economic outcomes of alcohol treatment using the Economic Form 90. AB - OBJECTIVE: This article assesses the ability of the economic outcome measures in the Economic Form 90 to detect differences across levels of alcohol dependence as measured by the Alcohol Dependence Scale. METHOD: We used baseline data from the Combining Medications and Behavioral Interventions (COMBINE) Study, a large, multisite clinical trial, to assess the extent to which the economic items on the Economic Form 90 instrument can detect differences across levels of alcohol dependence. RESULTS: After adjusting for differences in demographic characteristics, the Economic Form 90 can detect significant differences across a range of dependence severity levels for the economic outcomes of inpatient medical care, emergency-department medical care, behavioral health care, being on parole or probation, and missed workdays, conditional on being employed. We did not detect significant differences across dependence severity for employment status, outpatient medical care, other criminal justice involvement, or motor vehicle accidents. CONCLUSIONS: The Economic Form 90 can identify differences in many economic outcomes associated with differing levels of alcohol dependence. This suggests that the Economic Form 90 may be useful in assessing changes in economic outcomes that result from changes in alcohol dependence. PMID- 17286346 TI - Alcohol impairs the cognitive component of reaction time to an omitted stimulus: a replication and an extension. AB - OBJECTIVE: Research from a recent study indicates that cognitive performance is impaired by an acute dose of alcohol at blood alcohol concentrations (BACs) that do not affect motor performance. That study measured reaction time (RT) to the omission of a recurring stimulus and used behavioral criteria to fractionate premotor (cognitive) and motor components of RT when stimuli occurred at slow, 2 second intervals (0.5 Hz). The present experiment tested the generality of the evidence when stimuli occurred at slow or fast, 0.143-second intervals (7 Hz). Using muscle potential to fractionate RT, we tested the reproducibility of the findings obtained by a behavioral fractionation procedure. METHOD: Thirty male social drinkers were randomly assigned to two groups (n = 15 each) that received 0.8 g/kg alcohol or a placebo (0 g/kg). All participants performed a drug-free baseline test and a test during rising BACs. A test presented fast and slow frequency auditory stimuli in counterbalanced order within groups. RESULTS: Tests using both fast and slow frequency stimuli showed that alcohol slowed premotor RT and had no detectable effect on motor RT. CONCLUSIONS: Fractionated RT based on muscle potential reproduced the findings based on behavioral fractionation. The generality of the deleterious effects of alcohol on premotor RT was demonstrated by manipulating the frequency of the recurring stimuli. The consistent results obtained with the omitted stimulus paradigm provide a basis for new alcohol research that incorporates electrophysiological measures of the brain potential that are associated with the omission of a stimulus. PMID- 17286347 TI - Six-month changes in spirituality, religiousness, and heavy drinking in a treatment-seeking sample. AB - OBJECTIVE: This descriptive and exploratory study investigated change in alcoholics' spirituality and/or religiousness (S/R) from treatment entry to 6 months later and whether those changes were associated with drinking outcomes. METHOD: Longitudinal survey data were collected from 123 outpatients with alcohol use disorders (66% male; mean age = 39; 83% white) on 10 measures of S/R, covering behaviors, beliefs, and experiences, including the Daily Spiritual Experiences and Purpose in Life scales. Drinking behaviors were assessed with the Timeline Followback interview. Alcoholics Anonymous (AA) participation and attendance were also measured. RESULTS: Over 6 months, there were statistically significant increases in half of the S/R measures, specifically the Daily Spiritual Experiences scale, the Purpose in Life scale, S/R practices scale, Forgiveness scale, and the Positive Religious Coping scale. There were also clinically and statistically significant decreases in alcohol use. Multiple logistic regression analyses showed that increases in Daily Spiritual Experiences and in Purpose in Life scores were associated with increased odds of no heavy drinking at 6 months, even after controlling for AA involvement and gender. CONCLUSIONS: In the first 6 months of recovery, many dimensions of S/R increased, particularly those associated with behaviors and experiences. Values, beliefs, self-assessed religiousness, perceptions of God, and the use of negative religious coping did not change. Increases in day-to-day experiences of spirituality and sense of purpose/meaning in life were associated with absence of heavy drinking at 6 months, regardless of gender and AA involvement. The results of this descriptive study support the perspective of many clinicians and recovering individuals that changes in alcoholics' S/R occur in recovery and that such changes are important to sobriety. PMID- 17286348 TI - Impact of helping behaviors on the course of substance-use disorders in individuals with body dysmorphic disorder. AB - OBJECTIVE: Alcoholics Anonymous and 12-step facilitated treatments for substance use disorders (SUDs) encourage individuals with SUD to consider the needs of others and engage in helping behaviors as a method to become sober. SUDs are one of the most common comorbid disorders among individuals with body dysmorphic disorder (BDD). The purpose of this study is to examine prospectively the relationship between helping behaviors and the likelihood of SUD and BDD remission. METHOD: Data on 163 individuals during the course of 3 years were derived from the Prospective Study of Body Dysmorphic Disorder, a longitudinal investigation of patterns and predictors of the course of BDD. Kaplan-Meier survival estimates were used to calculate probabilities of time to BDD and SUD remission. Cox regression analyses were conducted to calculate the relative likelihood of levels of helping behaviors as time-varying predictors of remission from both SUD and BDD. RESULTS: The course of SUD and BDD was chronic for most subjects; the estimated probability of remission from an SUD across 3 years was .29 and .17 for a full BDD remission. Results indicated that increases in helping behaviors were significantly predictive of SUD remission (hazard ratio [HR] = 2.59, p = .0134). Helping behaviors were also predictive of BDD remission among those with or without SUD but at a trend level of significance (HR = 1.51, p = .0676). CONCLUSIONS: These findings extend previous work reporting significant relationships between helping behaviors and positive long-term SUD outcomes. Implications of the mechanisms involved in the link between helping behaviors and remission from SUD and BDD are discussed. PMID- 17286349 TI - Validity of self-reported drinking before injury compared with a physiological measure: cross-national analysis of emergency-department data from 16 countries. AB - OBJECTIVE: Self-reports of alcohol consumption among patients visiting an emergency department (ED) have been used extensively in the investigation of the relationship between drinking and injury. Little is known, however, about the associations between validity of self-reports with patient and injury characteristics and whether these relationships vary across regions or countries. Both of these issues are explored in this article. METHOD: In the construct of a multilevel logistical model, validity of self-reports was estimated as the probability of a positive self-report given a positive blood alcohol concentration (BAC). The setting included 44 EDs across 28 studies in 16 countries. Participants included 10,741 injury patients from the combined Emergency Room Collaborative Alcohol Analysis Project (ERCAAP) and the World Health Organization Collaborative Study of Alcohol and Injuries. Data were analyzed on self-reported drinking within 6 hours before injury compared with BAC results obtained from breath-analyzer readings in all but two studies, which used urine screens. Covariates included demographic, drinking, and injury characteristics and aggregate-level contextual variables. RESULTS: At the individual level, a higher BAC measurement was associated with a higher probability of reporting drinking, as was heavy drinking and sustaining injuries in traffic accidents or violence-related events. At the study level, neither aggregate BAC nor other sociocultural variables affected the validity of self reported drinking. CONCLUSIONS: This study provides further evidence of the validity of self-reported drinking measures in crossnational ED studies based on the objective criterion of BAC estimates. PMID- 17286351 TI - Calculation of the bulk modulus of simple and complex crystals with the chemical bond method. AB - The relation between the lattice energies and the bulk moduli on binary inorganic crystals was studied, and the concept of lattice energy density is introduced. We find that the lattice energy densities are in good linear relation with the bulk moduli in the same type of crystals, the slopes of fitting lines for various types of crystals are related to the valence and coordination number of cations of crystals, and the empirical expression of calculated slope is obtained. From crystal structure, the calculated results are in very good agreement with the experimental values. At the same time, by means of the dielectric theory of the chemical bond and the calculating method of the lattice energy of complex crystals, the estimative method of the bulk modulus of complex crystals was established reasonably, and the calculated results are in very good agreement with the experimental values. PMID- 17286350 TI - Recall bias for seven-day recall measurement of alcohol consumption among emergency department patients: implications for case-crossover designs. AB - OBJECTIVE: The purpose of this study was to estimate biases in recalling alcohol consumption over short periods. METHOD: Patients (n = 918) attending the surgical ward of the emergency department (ED) of the Lausanne University Hospital in Switzerland participated in a brief intervention study. Inclusion criteria were an average alcohol consumption exceeding 14 drinks per week for men or 7 drinks per week for women, or the consumption at least once monthly of 5 or more drinks for men or 4 or more drinks for women. Alcohol consumption was measured by means of a retrospective 7-day diary. RESULTS: Recalled alcohol consumption decreased with the length of the recall period. Consumption was 0.9 drinks lower for a recall of 7 days compared with a recall of 1 day. Biases were apparent for every day of the week, but the bias was highest for consumption to be recalled for Fridays and Saturdays. Recall bias was significant only for sporadic drinkers (those drinking less than 4 days a week) but not for regular drinkers (those drinking 5 or more days a week). CONCLUSIONS: Recall bias is a threat for survey measurements of alcohol consumption in general and particularly for research designs in which the bias is differentially distributed across cases and controls. This bias is true for case-crossover designs in which the recalled consumption of an individual for a period farther away from the interview (e.g., past week) serves as the control for the acute intake of the same individual (e.g., in the 6-hour period preceding ED attendance). Because risk estimates of case-crossover designs focus particularly on sporadic drinkers, the finding of recall biases being higher among sporadic drinkers increases the chance of spurious findings in such designs. PMID- 17286352 TI - Small-angle neutron scattering of mixed ionic perfluoropolyether micellar solutions. AB - Aqueous mixed micellar solutions of perfluoropolyether carboxylic salts with ammonium counterions have been studied by small-angle neutron scattering. Two surfactants differing in the tail length were mixed in proportions n2/n3 = 60/40 w/w, where n2 and n3 are the surfactants with two and three perfluoroisopropoxy units in the tail, respectively. The tails are chlorine-terminated. The mixed micellar solutions, in the concentration range 0.1-0.2 M and thermal interval 20 40 degrees C, show structural characteristics of the interfacial shell that are very similar to ammonium n2 micellar solutions previously investigated; thus, the physics of the interfacial region is dominated by the polar head and counterion. The shape and dimensions of the micelles are influenced by the presence of the n3 surfactant, whose chain length in the micelle is 2 A longer than that of the n2 surfactant. The n3 surfactant favors the ellipsoidal shape in the concentration range 0.1-0.2 M with a 1/2 ionization degree of n2 micelles. The very low surface charge of the mixed micelles is attributed to the increase in hydrophobic interactions between the surfactant tails, due to the longer n3 surfactant molecules in micelles. The closer packing of the tails decreases the micellar curvature and the repulsions between the polar heads, by surface charge neutralization of counterions migrating from the Gouy-Chapman diffuse layer, leading to micellar growth in ellipsoids with greater axial ratios. PMID- 17286353 TI - Synthesis and mesophases of glycerate surfactants. AB - In the quest to rationally design novel mesophase systems the challenge remains to deconvolute the relationship between structure, composition, and function. In the current study, novel glycerol-derived surfactants with high negative interfacial areas and a preference for inverse phase behavior have been targeted and synthesized. This has been achieved by application of the rule-of-thumb afforded by the critical packing parameter (CPP), namely, that inverse phase behavior is favored by wedge-shaped molecules with relatively small head group versus chain volume. Highly splayed hydrophobes with exaggerated cross section such as oleyl (cis-octadec-9-enyl) hexahydrofarnesyl (3,7,11-trimethyl-dodecyl) and phytanyl (3,7,11,15-tetramethyl-hexadecyl) were particularly successful for this purpose across many variations of head group. The phase behavior of the binary system in water of many of these surfactants is relatively simple. Typically, cubic or inverse hexagonal phases exist at the interface with water with the inverse micellar phases present at lower hydration. The inverse liquid crystalline phases were present for a broad range of temperatures and compositions. PMID- 17286354 TI - Poly(ethylene glycol)-conjugated phospholipids in aqueous micellar solutions: hydration, static structure, and interparticle interactions. AB - By means of dielectric relaxation spectroscopy (DRS) and small-angle X-ray scattering (SAXS), we have investigated hydration behavior, solvent dynamics, and static structures of aqueous solutions of poly(ethylene glycol)-conjugated distearoyl phosphatidylethanolamine (DSPE-PEG) (molecular weight of PEG: M(PEG)= 2000, 5000, and 12,000 Da). A quantitative analysis of the bulk-water relaxation amplitude revealed the effective hydration number of a DSPE-PEG molecule per ethylene oxide monomer unit to be approximately 5.0-5.5, virtually independent of M(PEG). The overall hydration number of a DSPE-PEG molecule is ca. 20% higher than that of the corresponding normal PEG (without DSPE). This is attributed to both hydration of a charged head group of phosphoric acid in DSPE and a packing effect of PEG chains into micellar structures. The pair-distance distribution functions, p(r), extracted from the GIFT analysis of SAXS intensities show that the DSPE-PEGs form spherical-like micelles in water having the maximum diameter of approximately 16, 22, and 31 nm, respectively, for M(PEG) = 2000, 5000, and 12,000 Da and nearly identical aggregation numbers of 72 (+/-10%). The DSPE-PEG micelles behave as charged colloids whose interparticle interaction potential can be approximated by the screened Coulomb potential model. The extracted pair correlation function g(r) demonstrates that both electrostatic repulsion induced by the charged head group and excluded volume effects of the fully hydrated PEG layer contribute to repulsive interactions among the PEG-lipid micelles. This should be a key factor for the function of PEG lipids as a stabilizer of liposomes. PMID- 17286355 TI - Theoretical study of sum-frequency vibrational spectroscopy off electronic resonance on limonene chiral liquids. AB - The sum-frequency vibrational spectroscopy (SFVS) off electronic resonance on chiral liquids is analyzed using the approach of antisymmetric nonresonant vibrational Raman scattering tensor calculation, which is based on the direct Taylor expansion of electronic transition moments in vibrational normal coordinates. A single-excitation configuration interaction treatment is applied to compute the SFVS off electronic resonance for (R)-limonene molecules, and the model spectra compare favorably with experimental data. This direct evaluation approach may provide a method of computing antisymmetric nonresonant vibrational Raman polarizabilities and predicting and assigning the SFVS off electronic resonance on chiral liquids. PMID- 17286356 TI - Oriented attachment kinetics for ligand capped nanocrystals: coarsening of thiol PbS nanoparticles. AB - In this work, the growth kinetics of thiol-capped PbS nanoparticles was studied. Two-stage growth process was observed, which was controlled first by oriented attachment (OA) mechanism and then by the hybrid Ostwald ripening (OR) and OA mechanism. Different from the NaOH-ZnS system, where OA will occur between any two multilevel nanoparticles, an OA kinetic model only considering the attachment related to original particles was fitted well with the experimental results. Analysis reveals that this model may be a universal one to describe the OA crystal growth process of nanocrystals capped with easily destroyed ligands, such as thiol-ZnS in the previous report. The OA crystal growth characteristics determined by the surface agent were discussed and compared. We propose that with stronger surface capping, the OR growth of nanocrystals is hindered, which facilitates the size controlling via OA kinetics during nanosynthesis. PMID- 17286357 TI - Hydrogen bonding interactions of pyridine*+ with water: stepwise solvation of distonic cations. AB - The solvation energies of the pyridine*+ radical cation by 1-4 H2O molecules were determined by equilibrium measurements in a drift cell. The binding energies of the pyridine*+(H2O)n clusters are similar to the binding energies of protonated pyridine-water clusters, (C5H5NH+)(H2O)n, which involve NH+..OH2 bonds and different from those of the solvated benzene radical cation-water clusters, C6H6*+(H2O)n, which involve CHdelta+..OH2 bonds. These relations indicate that the observed pyridine*+ ions have the distonic *C5H4NH+ structures that can form NH+..OH2 bonds. The observed thermochemistry and ab initio calculations show that these bonds are not affected significantly by an unpaired electron at another site of the ion. Similar observations also identify the 2-fluoropyridine*+ distonic ion. The distonic structure is also consistent with the reactivity of pyridine*+ in H atom transfer, intra-cluster proton transfer and deprotonation reactions. The results present the first measured stepwise solvation energies of distonic ions, and demonstrate that cluster thermochemistry can identify distonic structures. PMID- 17286358 TI - Electron attachment to SF5X compounds: SF5C6H5, SF5C2H3, S2F10, and SF5Br, 300 550 K. AB - Rate constants and ion product channels have been measured for electron attachment to four SF5 compounds, SF5C6H5, SF5C2H3, S2F10, and SF5Br, and these data are compared to earlier results for SF6, SF5Cl, and SF5CF3. The present rate constants range over a factor of 600 in magnitude. Rate constants measured in this work at 300 K are 9.9+/-3.0x10(-8) (SF5C6H5), 7.3+/-1.8x10(-9) (SF5C2H3), 6.5+/-2.5x10(-10) (S2F10), and 3.8+/-2.0x10(-10) (SF5Br), all in cm3 s-1 units. SF5- was the sole ionic product observed for 300-550 K, though in the case of S2F10 it cannot be ascertained whether the minor SF4- and SF6- products observed in the mass spectra are due to attachment to S2F10 or to impurities. G3(MP2) electronic structure calculations (G2 for SF5Br) have been carried out for the neutrals and anions of these species, primarily to determine electron affinities and the energetics of possible attachment reaction channels. Electron affinities were calculated to be 0.88 (SF5C6H5), 0.70 (SF5C2H3), 2.95 (S2F10), and 2.73 eV (SF5Br). An anticorrelation is found for the Arrhenius A-factor with exothermicity for SF5- production for the seven molecules listed above. The Arrhenius activation energy was found to be anticorrelated with the bond strength of the parent ion. PMID- 17286359 TI - Removal of NO in NO/N2, NO/N2/O2, NO/CH4/N2, and NO/CH4/O2/N2 systems by flowing microwave discharges. AB - In this paper, continuing previous work, we report on experiments carried out to investigate the removal of NO from simulated flue gas in nonthermal plasmas. The plasma-induced decomposition of small concentrations of NO in N2 used as the carrier gas and O2 and CH4 as minority components has been studied in a surface wave discharge induced with a surfatron launcher. The reaction products and efficiency have been monitored by mass spectrometry as a function of the composition of the mixture. NO is effectively decomposed into N2 and O2 even in the presence of O2, provided always that enough CH4 is also present in the mixture. Other majority products of the plasma reactions under these conditions are NH3, CO, and H2. In the absence of O2, decomposition of NO also occurs, although in that case HCN accompanies the other reaction products as a majority component. The plasma for the different reaction mixtures has been characterized by optical emission spectroscopy. Intermediate excited species of NO*, C*, CN*, NH*, and CH* have been monitored depending on the gas mixture. The type of species detected and their evolution with the gas composition are in agreement with the reaction products detected in each case. The observations by mass spectrometry and optical emission spectroscopy are in agreement with the kinetic reaction models available in literature for simple plasma reactions in simple reaction mixtures. PMID- 17286361 TI - Pauling resonant structures in real space through electron number probability distributions. AB - A general hierarchy of the coarsed-grained electron probability distributions induced by exhaustive partitions of the physical space is presented. It is argued that when the space is partitioned into atomic regions the consideration of these distributions may provide a first step toward an orbital invariant treatment of resonant structures. We also show that, in this case, the total molecular energy and its components may be partitioned into structure contributions, providing a fruitful extension of the recently developed interacting quantum atoms approach (J. Chem. Theory Comput. 2005, 1, 1096). The above ideas are explored in the hydrogen molecule, where a complete statistical and energetic decomposition into covalent and ionic terms is presented. PMID- 17286360 TI - Kinetics and mechanism of peroxyl radical reactions with nitroxides. AB - Cyclic nitroxides (>NO*) are stable radicals of diverse size, charge, lipophilicility, and cell permeability, which provide protection against oxidative stress via various mechanisms including SOD-mimic activity, oxidation of reduced transition metals and detoxification of oxygen- and nitrogen-centered radicals. However, there is no agreement regarding the reaction of nitroxides with peroxyl radicals, and many controversies in the literature exist. The question of whether nitroxides can protect by scavenging peroxyl radicals is important because peroxyl radicals are formed in biological systems. To further elucidate the mechanism(s) underlying the antioxidative effects of nitroxides, we studied by pulse radiolysis the reaction kinetics of piperidine, pyrrolidine, and oxazolidine nitroxides with several alkyl peroxyl radicals. It is demonstrated that nitroxides mainly reduce alkyl peroxyl radicals forming the respective oxoammonium cations (>N+=O). The most efficient scavenger of peroxyl radicals is 2,2,6,6-tetramethylpiperidine-N-oxyl (TPO), which has the lowest oxidation potential among the nitroxides tested in the present study. The rate constants of peroxyl reduction are in the order CH2(OH)OO*>CH3OO*>t-BuOO*, which correlate with the oxidation potential of these peroxyl radicals. The rate constants for TPO vary between 2.8x10(7) and 1.0x10(8) M-1 s-1 and for 3-carbamoylproxyl (3-CP) between 8.1x10(5) and 9.0x10(6) M-1 s-1. The efficacy of protection of nitroxides against inactivation of glucose oxidase caused by peroxyl radicals was studied. The results demonstrate a clear correlation between the kinetic features of the nitroxides and their ability to inhibit biological damage inflicted by peroxyl radicals. PMID- 17286362 TI - Chiral recognition in diaziridine clusters and the problem of racemization waves. AB - Theoretical calculations (B3LYP/6-31+G**) of chiral clusters of diaziridines have been carried out. Five configurations of chiral and nonchiral clusters with up to eight monomers have been considered. The proton transfer within the neutral and protonated clusters has been studied as a possible source of racemization waves. The optical rotatory power (ORP) has been calculated for the neutral and protonated homochiral clusters. The results show that the clusters with alternated chiral molecules are the preferred ones and that the proton transfer proceeds with low energetic barriers in the protonated systems. The ORP results are very dependent on the shape of the clusters and the neutral or protonated state of them. PMID- 17286363 TI - A quantitative scale for the degree of aromaticity and antiaromaticity: a comparison of theoretical and experimental enthalpies of hydrogenation. AB - Chemical structures and transition states are often influenced by aromatic stabilization or antiaromatic destabilizing effects, which are not easy to characterize theoretically. The exact description and precise quantification of the aromatic characteristics of ring structures is difficult and requires special theoretical investigation. The present paper suggests a novel, yet simple, method to quantify both aromatic and antiaromatic qualities on the same linear scale, by using the experimentally measured or theoretically computed enthalpy of hydrogenation reaction of the compound examined [DeltaHH2(examined)]. A reference hydrogenation reaction is also considered on a corresponding nonaromatic reference compound [DeltaHH2(reference)] to cancel all secondary structure destabilization factors, such as ring strain or double bond strain. From these data the relative enthalpy of hydrogenation may easily be calculated: DeltaDeltaHH2=DeltaHH2(examined)-DeltaHH2(reference). In the present work concept, the DeltaDeltaHH2 value of benzene defines the completely aromatic character (+100%), and the closed shell of the singlet cyclobutadiene represents maximum antiaromaticity (-100%). The component DeltaHH2 values were computed at different levels of theory offering a computational "method-independent" measure for aromaticity. A total of 28 well-known aromatic, antiaromatic and nonaromatic, neutral and charged compounds were examined to demonstrate the efficiency of this methodology. Finally, a correlation was made between the calculated aromaticity percentage of the compound examined and their popular Schleyers NICS values. PMID- 17286364 TI - Highly stereoselective radical carbonylations of gem-dihalocyclopropane derivatives with CO. AB - A couple of radical carbonylations of gem-dihalocyclopropanes 1 using CO and Bu3SnH (formylation) or Bu3Sn(CH2CH=CH2) (allylacylation) successfully proceeded to give trans and cis adducts (2 and 3) with good to excellent stereoselectivity (trans/cis = >99/1-75/25 or 17/83-1/99). The formylation of 2,3-cis-disubstituted 1,1-dihalocyclopropanes enhanced trans selectivity (trans/cis = >99/1-95/5), whereas both 2,3-cis-disubstituted and 2-monosubstituted 1,1-dihalocyclopropanes underwent allylacylation with nearly complete trans selectivity (trans/cis = >99/1). Inherently less reactive gem-dichloro- and bromochlorocyclopropanes than gem-dibromocyclopropanes served as favorable substrates. [reaction: see text]. PMID- 17286365 TI - Rapid access to pyrimido[5,4-c]isoquinolines via a sulfur monoxide extrusion reaction. AB - The scope of a sulfur monoxide extrusion reaction of pyrimido[4,5 b][1,4]benzothiazepines leading to pyrimido[5,4-c]isoquinolines was investigated. Thus, selective oxidation followed by nucleophilic displacement of the oxidized side chain sulfur group and subsequent extrusion reaction of sulfur monoxide in the ring, which can be conducted in a two-step sequence or in a one-pot procedure, produced novel pyrimido[5,4-c]isoquinolines, a class of compounds with potential biological and pharmaceutical applications. [reaction: see text]. PMID- 17286366 TI - Synthesis of 2-oxazolidinones from beta-lactams: stereospecific total synthesis of (-)-cytoxazone and all of its stereoisomers. AB - The synthetic correlation between two different antibiotic frameworks, the beta lactams and 2-oxazolidinones, is described for the first time. In this approach, 2-oxazolidinones are prepared in stereomerically pure form from 3-hydroxy beta lactams by a ring-opening-cyclization isomerization process. Application of this methodology to the total synthesis of the cytokine modulator, (-)-cytoxazone, and its three stereoisomers is demonstrated. [reaction: see text]. PMID- 17286367 TI - Asymmetric synthesis of substituted homoallyl alcohols, halomethyl tetrahydrofurans, and chloro-amino sulfones from allyltitanium sulfoximines and alpha-hetero aldehydes. AB - Asymmetric syntheses of the iodomethyl-substituted bicyclic tetrahydrofuran 22 and the chloro-amino sulfone 30 from the allylic sulfoximine 15 and the alpha hetero aldehydes 2 and 23, respectively, are described. Further examples for the asymmetric synthesis of chloromethyl tetrahydrofurans and chloro-amino sulfones are given. The synthesis of 30 features as key step the stereoselective Cl substitution of a hydroxy group under neighboring group participation by an aminosulfoxonium group which is converted to a sulfonyl group. [reaction: see text]. PMID- 17286368 TI - Selective monocyclization of epoxy terpenoids promoted by zeolite NaY. A short biomimetic synthesis of elegansidiol and farnesiferols B-D. AB - Epoxy terpenes cyclize readily, by confinement within zeolite NaY, to form exomethylenic cyclohexanols as the major products. The selective monocyclization of 10,11-epoxyfarnesyl acetate within NaY provides a short and efficient biomimetic route to (+/-)-elengasidiol and (+/-)-farnesiferols B-D. [reaction: see text]. PMID- 17286369 TI - Preliminary studies on the transformation of nitrosugars into branched chain iminosugars: synthesis of 1,4-dideoxy-4-C-hydroxymethyl-1,4-imino-pentanols. AB - A novel promising strategy for the transformation of nitrosugars into branched pyrrolidines, based on double Henry reaction with formaldehyde followed by reductive ring closure, allowed the first enantiospecific synthesis of a 4-C hydroxymethyl branched derivative of the well-known glycosidase inhibitor 1,4 dideoxy-1,4-imino-pentanol. This strategy also afforded a new route to some other interesting derivatives, such as N-hydroxy, N-propyloxy, and imino derivatives, a new kind of compounds with promising biological properties. [reaction: see text]. PMID- 17286370 TI - Gold(III)-catalyzed double hydroamination of o-alkynylaniline with terminal alkynes leading to N-vinylindoles. AB - A highly efficient double-hydroamination reaction of o-alkynylanilines with terminal alkynes leading to N-alkenylindoles was developed by using gold(III) as a catalyst under neat conditions. [reaction: see text]. PMID- 17286371 TI - Cu-catalyzed N- and O-arylation of 2-, 3-, and 4-hydroxypyridines and hydroxyquinolines. AB - With use of Cu-based catalysts, 2- and 4-hydroxypyridines were N-arylated in modest to excellent yields. In the case of 2-hydroxypyridine, the use of 4,7 dimethoxy-1,10-phenanthroline, 3, expanded the scope of previous literature reports to include the use of N-containing heteroaryl halides, and 2-substituted aryl halides. In addition, by using a copper catalyst based on 2,2,6,6 tetramethylheptane-3,5-dione, 4, the first N-arylations of 4-hydroxypyridines and O-arylations of 3-hydroxypyridines with aryl bromides and iodides have been accomplished. [reaction: see text]. PMID- 17286372 TI - Synthesis of (+)-madindoline A and (+)-madindoline B. AB - The allene ether version of the Nazarov cyclization was used to construct the cyclopentane dione portion of madindolines A and B. The racemic cyclopentane dione from the Nazarov cyclization was converted to an enol ether that was combined with the chiral, nonracemic hydroxyfuroindoline in a Mannich reaction. Deprotection and oxidation led to (+)-madindoline A and (+)-madindoline B. [reaction: see text]. PMID- 17286373 TI - 3-Mercaptopropanol as a traceless linker for chemical and enzymatic synthesis of oligosaccharides. AB - The reducing end of protected carbohydrates can be equipped with a series of aglycones via the photochemical installation of a 3-mercaptoethanol linker. This linker is stable during chemical and enzymatic glycosylation reactions but can be activated readily and efficiently to couple oligosaccharides with different nucleophiles. This approach provides straightforward access to a range of molecules that serve as probes for carbohydrate modifying enzymes. [reaction: see text]. PMID- 17286374 TI - Titanium- and Lewis acid-mediated cyclopropanation of imides. AB - We report a straightforward synthesis of 1-azaspirocyclopropane lactams from imides. Following the described procedure, polycyclic nitrogen heterocycles containing a cyclopropane unit could be obtained from unsaturated imides. [reaction: see text]. PMID- 17286375 TI - Selective desulfurization of cysteine in the presence of Cys(Acm) in polypeptides obtained by native chemical ligation. AB - Increased versatility for the synthesis of proteins and peptides by native chemical ligation requires the ability to ligate at positions other than Cys. Here, we report that Raney nickel can be used under standard conditions for the selective desulfurization of Cys in the presence of Cys(Acm). This simple and practical tactic enables the more common Xaa-Ala junctions to be used as ligation sites for the chemical synthesis of Cys-containing peptides and proteins. [reaction: see text]. PMID- 17286376 TI - Isolation, structure determination, and anti-cancer activity of apoptolidin D. AB - The isolation, characterization, and preliminary biological activity of apoptolidin D, a new apoptolidin that exhibits anti-proliferative activity against H292 human lung carcinoma cells at nanomolar concentrations, are reported. Its equilibration with isoapoptolidin D and characterization of the latter are also described. [structure: see text]. PMID- 17286377 TI - Multiple on-resin olefin metathesis to form ring-expanded analogues of the lantibiotic peptide, lacticin 3147 A2. AB - Chemical synthesis of lantibiotic analogues wherein monosulfide bridges are replaced with other groups can shed light on structure-activity relationships and generate variants that are resistant to aerobic oxidation and have better metabolic stability. This work describes the first complete synthesis of a carbocyclic lantibiotic analogue 2, using sequential on-resin ring-closing olefin metathesis and solution-phase peptide synthesis. The methodology described should find wide application for the preparation of rigidified peptidomimetics containing multiple carbocyclic rings. [structure: see text]. PMID- 17286378 TI - Diastereoselective synthesis of the pectenotoxin 2 non-anomeric AB spiroacetal. AB - The reductive cyclization reaction of a cyanoacetal has been used to prepare the pectenotoxin 2 (PTX-2) AB spiroacetal with high diastereoselectively for the first time. The strategy is convergent and makes use of the axial-selective reductive lithiation of 2-cyano tetrahydropyran rings to introduce the spiroacetal center with the desired non-anomeric selectivity. [reaction: see text]. PMID- 17286379 TI - A modular approach to marine macrolide construction. 4. Assembly of C36-C51 and C29-C44 building blocks and evaluation of key coupling reactions targeting spongistatin 1 (altohyrtin A). AB - Routes have been developed for the stereocontrolled elaboration of two highly functionalized sectors of spongistatin 1. The approach to ring F takes advantage of B-alkyl Suzuki-Miyaura coupling to install the C44-C45 bond. The E-ring pyran moiety was generated by acylation of an alpha-sulfonyl carbanion, the stereogenic centers of which were incorporated by sequential asymmetric aldol reactions. [structure: see text]. PMID- 17286382 TI - [2+2] photocyclization in a solid-state transformation of a TTF-benzonitrile. PMID- 17286380 TI - Operationally simple and efficient workup procedure for TBAF-mediated desilylation: application to halichondrin synthesis. AB - An operationally simple and efficient workup method for tetrabutylammonium fluoride (TBAF)-mediated t-butyldimethylsilyl (TBS) deprotection has been developed. The procedure includes addition of a sulfonic acid resin and calcium carbonate, followed by filtration and evaporation. This method eliminates the tedious aqueous-phase extraction process to remove excess TBAF and materials derived from TBAF, thereby making the protocol highly amenable to multiple TBS deprotections. Its efficiency and usefulness were demonstrated by using the transformation of 1a to 3a in the halichondrin synthesis. [reaction: see text]. PMID- 17286383 TI - Molecular dynamics simulations of solvated crystal models of cellulose I(alpha) and III(I). AB - Swelling behaviors of cellulose I(alpha) and III(I) crystals have been studied using molecular dynamics simulations of the solvated finite-crystal models. The typical crystal models consisted of 48 x 10-mer chains. For the cellulose I(alpha) crystal, models consisting of different numbers of chains and chain lengths were also studied. The structural features of the swollen crystal models, including the cellulose I(beta) crystal model reported previously, were compared. A distinct right-handed twist was observed for models of the native cellulose crystals (cellulose I(alpha) and I(beta)), with a greater amount of twisting observed for the I(alpha) crystal model. Although the amount of twist decreased with increasing dimensions of the cellulose I(alpha) crystal model, the relative changes in twist angle suggest that considerable twist would arise in a crystal model of the actual dimensions. In contrast to the swelling behavior of crystal models of the native cellulose, the cellulose III(I) crystal model exhibited local, gradual disordering at the corner of the reducing end. Comparison of the lattice energies indicated that the cellulose chains of the I(beta) crystal were packed in the most stable fashion, whereas those of the I(alpha) and III(I) crystals were in a metastable state, which is consistent with the crystallization behaviors observed. Upon heating of the native cellulose crystal models, the chain sheets of the I(alpha) model showed a continuous increase in twist angle, suggesting weaker intersheet interactions in this model. The swollen crystal models of cellulose I(alpha) and III(I) reproduce well the representative structural features observed in the corresponding crystal structures. The crystal model twist thus characterizes the swelling behavior of the native cellulose crystal models, which seems to be related to the insolubility of the crystals. PMID- 17286384 TI - Encapsulation of viral vectors for gene therapy applications. AB - In gene therapy, a number of viruses are currently being used as vectors to provide transient expression of therapeutic proteins. A drawback of using free virus is that it gives a potent immune response, which reduces gene transfer and limits re-administration. An alternative delivery system is to encapsulate the virus in poly(lactide-co-glycolide) (PLG) microspheres prior to administration. A recombinant adenovirus (Ad) expressing green fluorescent protein (GFP) was used to test the transduction efficiency of Ad encapsulated in microspheres on target cells. The number of infected cells that expressed GFP was measured by flow cytometry. It was demonstrated that encapsulated viral vectors could successfully transduce target cells with encapsulation efficiencies up to 23% and that the level of transduction could be controlled by varying both the quantity of microspheres and the amount of Ad in the microspheres. High transduction efficiencies and its recognized biocompatibility make PLG-encapsulated Ad an attractive alternative to the use of free virus in gene therapy applications. The infectivity of Ad was found to be significantly influenced by the processing conditions and changes in environmental factors. Free Ad and encapsulated Ad were able to infect both E1 complimenting cells (HEK 293) and non-complimenting cells (A549), with the viral expression in HEK 293 cells being 2.1 times greater than for A549 cells. PMID- 17286385 TI - Effect of extracellular ph on matrix synthesis by chondrocytes in 3D agarose gel. AB - In cartilage tissue engineering, the determination of the most appropriate cell/tissue culture conditions to maximize extracellular matrix synthesis is of major importance. The extracellular pH plays an important role in affecting energy metabolism and matrix synthesis by chondrocytes. In this study, chondrocytes were isolated from bovine articular cartilage, embedded in agarose gel, and cultured at varied pH levels (7.3-6.6). Rate of lactate production, total glycosaminoglycan (GAG) and collagen synthesis, as well as total cell numbers and cell viability were evaluated after culturing for up to 7 days. The results showed the rate of lactic acid production over the 7-day culture was significantly affected by extracellular pH; acidic pH markedly inhibited the production of lactate. Also, a biphasic response to extracellular pH in regard to total GAG synthesis was observed; the maximum synthesis was seen at pH 7.2. However, the collagen synthesis was not pH-dependent within the pH range explored. In addition, within the conditions studied, total cell numbers and cell viability were not significantly affected by extracellular pH. In conclusion, even minor changes in extracellular pH could markedly affect the metabolic activities and biosynthetic ability of chondrocytes. Consequently, the control of extracellular pH condition is crucially important for successful cartilage tissue engineering and for the study of chondrocyte physiology and functions. PMID- 17286386 TI - Comparative evaluation of different DNA extraction procedures from food samples. AB - Five methodologies for extracting DNA from food samples are described. The food products analyzed are from either soybean or maize. They were selected on the basis of the mechanical, thermal, and chemical treatments that they had been subjected to during industrial processing. DNA preparations were evaluated for purity, yield, and average fragment size. Two endogenous genes, soybean lectin gene and alcohol dehydrogenase gene (adh1), were used to assess the degree of DNA degradation at different stages of the transformation chain. The goal of this study was to determine the role that extraction methods play in DNA amplification in order to select the best protocol for a food sample. This comparative evaluation can be specifically useful for detection of genetically modified ingredients in a variety of food matrices. PMID- 17286387 TI - A nonoxidative sensor based on a self-doped polyaniline/carbon nanotube composite for sensitive and selective detection of the neurotransmitter dopamine. AB - Most of the current techniques for detection of dopamine exploit its ease of oxidation. However, the oxidative approaches suffer from a common problem. The products of dopamine oxidation can react with ascorbic acid present in samples and regenerate dopamine again, which severely limits the accuracy of detection. In this paper, we report a nonoxidative approach to electrochemically detect dopamine with high sensitivity and selectivity. This approach takes advantage of the high performance of our newly developed poly(anilineboronic acid)/carbon nanotube composite and the excellent permselectivity of the ion-exchange polymer Nafion. The binding of dopamine to the boronic acid groups of the polymer with large affinity affects the electrochemical properties of the polyaniline backbone, which act as the transduction mechanism of this nonoxidative dopamine sensor. The unique reduction capability and high conductivity of single-stranded DNA functionalized, single-walled carbon nanotubes greatly improved the electrochemical activity of the polymer in physiological buffer, and the large surface area of the carbon nanotubes largely increased the density of the boronic acid receptors. The high sensitivity along with the improved selectivity of this sensing approach is a significant step forward toward molecular diagnosis of Parkinson's disease. PMID- 17286388 TI - Solvent isotope effects in reactions of human medium-chain acyl-CoA dehydrogenase active site mutants. AB - Glu376, the base involved in substrate alphaH+ abstraction at the active center of medium-chain acyl-CoA dehydrogenase (MCAD), has been mutated to Gln and Gly. The mutants are active; however, their rates of dehydrogenation are lowered by approximately 5 orders of magnitude. Binding of the substrate octanoyl-CoA to Glu376Gln-MCAD involves (at least) two steps. The ensuing dehydrogenation reaction that corresponds to reduction of the flavin cofactor also occurs in two phases. These are interpreted to consist of a first, reversible step, followed by a slower, practically irreversible one. For Glu376Gln-MCAD, the log of the rates of dehydrogenation increases linearly with pH (slope = 1) in the pH range of 6 10, suggesting HO- as a reactant. The rates of the same reactions in D2O have the same pD profile and reflect a solvent kinetic isotope effect (SKIE) of approximately 8.5. Glu376Gln+Glu99Gly-MCAD (studied to assess the role of Glu99 also present at the bottom of the active center cavity) has activities and activity profiles similar to those of Glu376Gln-MCAD. This excludes Glu99 as the active center base for Glu376Gln-MCAD catalysis. Proton inventories for the two phases of the dehydrogenation reaction were investigated at 4 and 25 degrees C. The inventories at 25 degrees C reflect a SKIE of approximately 4.5; the profiles are "bowl-shaped", in which a transition-state contribution predominates. The profiles for the 4 degrees C reaction are very unusual. That for the first phase can be analyzed on a two-step model with one step (80% rate-limiting) having a conformational reorganization with an isotope effect of 90-100, from small isotope effects at many protein sites, and the other step (20% rate-limiting) having an inverse isotope effect of ca. 2, characteristic of the reaction of hydroxide ion as a base. For the second phase, only a contribution from many protein sites with a KIE of approximately 4.5 is observed. The results are compatible with a very rigid active site framework that must undergo rearrangements for dehydrogenation to take place, and specifically to allow access of HO-, the reactant that must neutralize the H+ abstracted from the alphaC-H substrate. The large isotope effects are attributed to the changes in state of several H-bonds that occur during the process. PMID- 17286389 TI - Employing mutants to study thrombin residues responsible for factor XIII activation peptide recognition: a kinetic study. AB - In the last stages of coagulation, thrombin helps to activate Factor XIII. The resultant transglutaminase introduces covalent cross-links into fibrin thus promoting clot stability. To better understand the roles of individual thrombin residues in recognition and hydrolysis of the Factor XIII activation peptide, mutations within thrombin's aryl and apolar binding site were explored. The thrombin mutants W215A, E217A, W215A/E217A, L99A, and I174A were examined through HPLC kinetics against the substrates FXIII (28-41) V34 AP and FXIII (28-41) V34L AP. Several mutants responded differently to FXIII (28-41) V34 AP vs the cardioprotective V34L AP. W215 provides an important platform for binding and directing FXIII APs for proper hydrolysis. Loss of this platform leads to decreases in kinetics, particularly to the kcat of FXIII V34L AP. E217 also plays a supporting role, but the E217A mutation is not as detrimental as W215A. W215A/E217A is unfavorable for both activation peptides and its coupling effect has been characterized. This mutant can readily bind the peptides but cannot orient them for effective hydrolysis. Kinetic studies with I174A indicate that this thrombin residue is more crucial for interactions with the larger V34L AP segment. The L99A mutation causes deleterious effects to binding and hydrolysis of both APs. The V34L, however, is able to partially compensate for the loss perhaps by increasing contact within the aryl and apolar sites. Understanding how specific FXIII and thrombin residues participate in binding and control hydrolysis may lead to the design of coagulation enzymes whose degree of activation and optimal target site can be controlled. PMID- 17286391 TI - Enthalpies of formation, bond dissociation energies and reaction paths for the decomposition of model biofuels: ethyl propanoate and methyl butanoate. AB - The complete basis set method CBS-QB3 has been used to study the thermochemistry and kinetics of the esters ethyl propanoate (EP) and methyl butanoate (MB) to evaluate initiation reactions and intermediate products from unimolecular decomposition reactions. Using isodesmic and isogeitonic equations and atomization energies, we have estimated chemically accurate enthalpies of formation and bond dissociation energies for the esters and species derived from them. In addition it is shown that controversial literature values may be resolved by adopting, for the acetate radical, CH3C(O)O(.-), DeltaH(o)(f)298.15K) = -197.8 kJ mol(-1) and for the trans-hydrocarboxyl radical, C(.-)(O)OH, -181.6 +/- 2.9 kJ mol(-1). For EP, the lowest energy decomposition path encounters an energy barrier of approximately 210 kJ mol(-1) (approximately 50 kcal mol(-1)), which proceeds through a six-membered ring transition state (retro-ene reaction) via transfer of the primary methyl H atom from the ethyl group to the carbonyl oxygen, while cleaving the carbon-ether oxygen to form ethene and propanoic acid. On the other hand, the lowest energy path for MB has a barrier of approximately 285 kJ mol(-1), producing ethene. Other routes leading to the formation of aldehydes, alcohols, ketene, and propene are also discussed. Most of these intramolecular hydrogen transfers have energy barriers lower than that needed for homolytic bond fission (the lowest of which is 353 kJ mol(-1) for the C(alpha) C(beta) bond in MB). Propene formation is a much higher energy demanding process, 402 kJ mol(-1), and it should be competitive with some C-C, C-O, and C-H bond cleavage processes. PMID- 17286390 TI - Phosphorylation and functions of inhibitor-2 family of proteins. AB - Protein phosphatase-1 (PP1) is an essential protein Ser/Thr phosphatase that is extraordinarily conserved from yeast to human, and Inhibitor-2 (I-2) is the most ancient of the heat-stable proteins specific for PP1. We identified novel I-2 homologues in Caenorhabditis elegans (Ce) and Xenopus laevis (Xe) and compared them to the I-2 proteins from Homo sapiens (Hs), Saccharomyces cerevisiae (GLC8), and Drosophila melanogaster (Dm). The Ce I-2 and Dm I-2 showed the highest potency inhibition of rabbit PP1 with IC50 near 5 nM compared to Hs I-2 and Xe I 2 with IC50 between 10 and 50 nM and GLC8 with >100-fold lower activity. Inhibition of PP1 bound to Nek2 kinase activated the kinase to phosphorylate a C Nap1 domain substrate. All the species of I-2 except GLC8 activated the Nek2::PP1 to the same extent as microcystin-LR. Only Hs I-2 and Xe I-2, not the I-2 proteins more divergent in sequence, directly activated human Aurora-A kinase. Various species of I-2 have a common PxTP phosphorylation site that showed a wide range of reactivity with GSK3, ERK, or CDC2/cyclinB1 kinases. The Suc1 subunit of CDC2/cyclinB1 enhanced reactivity with I-2, consistent with this being a site of mitotic phosphorylation. The results show species specificity among the I-2 family within the context of conserved PP1 inhibitory activity and variable phosphorylation by Pro-directed kinases. PMID- 17286392 TI - Synthesis and characterization of a platinum(II) complex tethered to a ligand of the peripheral benzodiazepine receptor. AB - A peripheral benzodiazepine receptor (PBR) ligand (TZ6, 5) has been selected as receptor-mediated carrier for antitumor cisplatin-like compounds. Compound 5, containing a thiazole ring in position 2 of the imidazopyridine nucleus, is able to act as a dinitrogen chelate toward platinum. The resulting complex, cis [PtCl2(5)], that is, compound 8, has been fully characterized by NMR techniques and has been shown to possess affinity and selectivity for the PBR comparable to those of 5 (IC50 of 4.6 and 2.81 nM for 8 and 5, respectively; selectivity indexes for PBR greater than 10,000 for both compounds). Hence, a platinum moiety cross-linking the imidazopyridine and the thiazole aromatic rings does not alter the affinity for PBR. The same cross-linking could be responsible for the tendency of 8 to associate in dimers. The equilibrium between monomer and dimer has been investigated by NMR spectroscopy and the corresponding constant determined. PMID- 17286393 TI - Potent antitubulin tumor cell cytotoxins based on 3-aroyl indazoles. AB - A series of 3-aroyl indazoles was synthesized. Modification of the C-7 position resulted in a significant structure-activity relationship (SAR) with acetylene modifications conferring unusual potency in a tumor cell cytotoxicity assay. The most potent compounds exceeded the activity of combretastatin A4 (CA-4), showing single digit nM IC50 values against all cell lines tested including those with known efflux resistance pumps. The inhibition of in vitro tubulin polymerization was comparable to CA-4, consistent with tubulin being the target for these compounds. Competition binding experiments employing [3H]colchicine and purified tubulins demonstrated that the compound specifically binds to the colchicine site. PMID- 17286395 TI - Clustering and rule-based classifications of chemical structures evaluated in the biological activity space. AB - Classification methods for data sets of molecules according to their chemical structure were evaluated for their biological relevance, including rule-based, scaffold-oriented classification methods and clustering based on molecular descriptors. Three data sets resulting from uniformly determined in vitro biological profiling experiments were classified according to their chemical structures, and the results were compared in a Pareto analysis with the number of classes and their average spread in the profile space as two concurrent objectives which were to be minimized. It has been found that no classification method is overall superior to all other studied methods, but there is a general trend that rule-based, scaffold-oriented methods are the better choice if classes with homogeneous biological activity are required, but a large number of clusters can be tolerated. On the other hand, clustering based on chemical fingerprints is superior if fewer and larger classes are required, and some loss of homogeneity in biological activity can be accepted. PMID- 17286396 TI - First-row transition-metal complexes based on a carboxylate polychlorotriphenylmethyl radical: trends in metal-radical exchange interactions. AB - We report the synthesis, crystal structures, and magnetic properties of a series of mononuclear, metal-radical complexes with first-row transition-metal ions using a new class of radical-based ligands, the polychlorinated triphenylmethyl (PTM) radicals. Crystal structures of three new PTM-based complexes of general formula M(PTMMC)2(py)4-x(H2O)x [PTMMC = PTM radical functionalized at the para position with one carboxylic group; M = Zn(II), x = 2 (1); M = Ni(II), x = 1 (2); M = Co(II), x = 1 (3)] show similar molecular structures in which mononuclear complexes are formed by an octahedral metal ion coordinated by two monodentated PTMMC units. From a magnetic point of view, these similar configurations describe a quasilinear, trimeric magnetic model (PTMMC-M(II)-PTMMC), in which the metal [Ni(II) or Co(II)]-radical magnetic-exchange coupling constants have been determined for the first time. In all of these complexes, the temperature dependence of the magnetic susceptibility reveals moderate antiferromagnetic exchange coupling constants between the PTMMC radicals and Ni(II) (2J/kB = -47.1 K) and Co(II) ions (2J/kB = -15.2 K) based on the exchange Hamiltonian H = 2JSM(Srad1 + Srad2). PMID- 17286397 TI - Three guest-including coordination solids from a single crystallization: a discrete cage and open-channel networks from 1-d ladders and 1-d ribbons. AB - A study of the coordination assemblies that result from the complexation of 1,3,5 tri(4-sulfophenyl)benzene, L3-, with copper(II) in the presence of pyridine is presented. The present results offer some insights into the subtleties of designing coordination polymers and open-channel solids. From an initial crystallization, three different single crystalline solids, 1-3, are obtained. Compounds 1 and 2 are Cu pyridyl complexes of the trianionic form of the ligand whereas compound 3 is a Cu pyridyl complex of the monoprotonated form, HL2-. Compound 1 is a discrete cage complex. Compound 2 is a 1-D ladder structure that has open channels, and compound 3 is a 1-D ribbon structure that assembles into open channels. All three complexes form from the same crystallization in a ratio of 90:9:1, and all three have the same Cu coordination sphere. The exact ratio of products can be altered by varying the Cu counterion or by the addition of methanol. Addition of hexamethylenetetramine results in the exclusive formation of a different network, 4, which is structurally almost identical to the minor product 3. Single-crystal structures of all four solids are presented along with thermal analysis and IR data for the major products. A number of insights into formation of coordination assemblies are obtained. Compound 3 is discussed as an intermediate to 2, and compounds 3 and 4 offer a design paradigm for the formation of open-channel solids from 1-D building blocks. PMID- 17286399 TI - Synthesis and characterization of copper(II) complexes of nonfacially coordinating heteroscorpionate ligands (4-carboxyphenyl)bis(3,5 dimethylpyrazolyl)methane and (3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane. AB - Complexes of Cu(II) derived from two new nonfacially coordinating heteroscorpionate ligands, (4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane (L4c) and (3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane (L3c), have been synthesized and characterized by X-ray diffraction, ESI-MS, IR, and UV-vis spectroscopy, electrochemistry, and magnetic susceptibility. The use of these new complexes as building blocks for the construction of supramolecular architectures is discussed. PMID- 17286398 TI - Characterization of Co-C bonding in dichlorovinylcobaloxime complexes. AB - This study combines theory and experiment in an examination of Co-C bonding and reductive Co-C cleavage in cobalt dichlorovinyl complexes. It is motivated by the role of dichlorovinyl complexes as intermediates in the dechlorination of trichloroethylene by cobalamin and cobalamin model complexes. A series of seven cis-1,2-dichlorovinyl(L)cobaloxime complexes were prepared (L = m- and p substituted pyridines; cobaloxime = bis(dimethylglyoximato)cobalt). The complexes were characterized using 1H NMR, 13C NMR, cyclic voltammetry, and X-ray crystallography. Examination of the metrical parameters of the Co-C=C unit across the series shows very little change in the C=C bond length and a slight increase in the Co-C bond length with increasing electron-donating ability of the pyridine ligand. These structural changes along with electronic structure calculations indicate that Co-C pi-bonding is not important in these complexes. The stronger Co-C bonds of vinylcobaloximes compared to those of alkylcobaloximes are best explained by the higher s character at C. Changes in the reduction potential across the series indicate that the pyridine-bound form is the primary electrochemically active species. Theoretical examination of the Co-C cleavage following reduction supports the direct formation of the cis-1,2-dichlorovinyl anion and not the cis-1,2-dichlorovinyl radical. PMID- 17286400 TI - Fe(II) mononuclear complexes with a new aminopyridyl ligand bearing a pivaloylamido arm. Preparation and spectroscopic characterizations of a Fe(III) hydroperoxo complex with oxygen and nitrogen donors. AB - Two new mononuclear FeII complexes, [(L52aH)FeII](PF6)2 (1-(PF6)2) and [(L52a)FeII]BPh4 (2-(BPh4)) have been synthesized with the new aminopyridyl ligand bearing a pivaloylamido arm L52aH (2,2-dimethyl-N-[6-({[2-(methyl-pyridin 2-ylmethyl-amino)-ethyl]-pyridin-2-ylmethyl-amino}-methyl)-pyridin-2-yl] propionamide), or its deprotonated form L52a-. The structures of the ferrous complexes have been determined by X-ray analysis. The mononuclear FeII is in a pseudo-octahedral environment in both complexes, the six positions around the metal center being occupied by five nitrogen atoms and one oxygen atom from the ligand. Whatever the protonation state of the amide function, the structures are very similar, the FeII being 6-fold coordinated by the two amines, three pyridines, and the oxygen atom from the ligand. These two complexes exhibit an acid/base equilibrium in solution that has been studied by UV-vis spectroscopy and cyclic voltammetry in acetonitrile. The reactivity of 1-(PF6)2 with H2O2 in methanol affords the formation of a new low-spin FeIII(OOH) intermediate in which the oxygen atom is retained in the coordination sphere of the metal. PMID- 17286401 TI - Electronic structure of ferric heme nitrosyl complexes with thiolate coordination. AB - The effect of trans thiolate ligation on the coordinated nitric oxide in ferric heme nitrosyl complexes as a function of the thiolate donor strength, induced by variation of NH-S(thiolate) hydrogen bonds, is explored. Density functional theory (DFT) calculations (BP86/TZVP) are used to define the electronic structures of corresponding six-coordinate ferric [Fe(P)(SR)(NO)] complexes. In contrast to N-donor-coordinated ferric heme nitrosyls, an additional Fe-N(O) sigma interaction that is mediated by the dz2/dxz orbital of Fe and a sigma*-type orbital of NO is observed in the corresponding complexes with S-donor ligands. Experimentally, this is reflected by lower nu(N-O) and nu(Fe-N) stretching frequencies and a bent Fe-N-O moiety in the thiolate-bound case. PMID- 17286402 TI - Reactions of monomeric [1,2,4-(Me3C)3C5H2]2CeH and CO with or without H2: an experimental and computational study. AB - Addition of CO to [1,2,4-(Me3C)3C5H2]2CeH,Cp'2 CeH, in toluene yields the cis (Cp'2Ce)2(mu-OCHCHO), in which the cis-enediolate group bridges the two metallocene fragments. The cis-enediolate quantitatively isomerizes intramolecularly to the trans-enediolate in C6D6 at 100 degrees C over 7 months. When the solvent is pentane, Cp'2Ce(OCH2)CeCp'2 forms, in which the oxomethylene group or the formaldehyde dianion bridges the two metallocene fragments. The cis enediolate is suggested to form by insertion of CO into the Ce-C bond of Cp'2Ce(OCH2)CeCp'2, generating Cp'2CeOCH2COCeCp'2. The stereochemistry of the cis enediolate is determined by a 1,2-hydrogen shift in the OCH2CO fragment that has the OC(H2) bond anti-periplanar relative to the carbene lone pair. The bridging oxomethylene complex reacts with H2, but not with CH4, to give Cp'2CeOMe, which is also the product of the reaction between Cp'2CeH and a mixture of CO and H2. The oxomethylene complex reacts with CO to give the cis-enediolate complex. DFT calculations on C5H5 model metallocenes show that the reaction of Cp2CeH with CO and H2 to give Cp2CeOMe is exoergic by 50 kcal mol-1. The net reaction proceeds by a series of elementary reactions that occur after the formyl complex, Cp2Ce(eta2-CHO), is formed by further reaction with H2. The key point that emerges from the calculated potential energy surface is the bifunctional nature of the metal formyl in which the carbon atom behaves as a donor and acceptor. Replacing H2 by CH4 increases the activation energy by 17 kcal mol-1. PMID- 17286403 TI - Concerted molecular displacements in a thermally-induced solid-state transformation in crystals of DL-norleucine. AB - Martensitic transformations are of considerable technological importance, a particularly promising application being the possibility of using martensitic materials, possibly proteins, as tiny machines. For organic crystals, however, a molecular level understanding of such transformations is lacking. We have studied a martensitic-type transformation in crystals of the amino acid DL-norleucine using molecular dynamics simulation. The crystal structures of DL-norleucine comprise stacks of bilayers (formed as a result of strong hydrogen bonding) that translate relative to each other on transformation. The simulations reveal that the transformation occurs by concerted molecular displacements involving entire bilayers rather than on a molecule-by-molecule basis. These observations can be rationalized on the basis that at sufficiently high excess temperatures, the free energy barriers to concerted molecular displacements can be overcome by the available thermal energy. Furthermore, in displacive transformations, the molecular displacements can occur by the propagation of a displacement wave (akin to a kink in a carpet), which requires the molecules to overcome only a local barrier. Concerted molecular displacements are therefore considered to be a significant feature of all displacive transformations. This finding is expected to be of value toward developing strategies for controlling or modulating martensitic-type transformations. PMID- 17286404 TI - Design, synthesis, and characterization of binuclear Ni(II) complexes with inherent helical chirality. PMID- 17286405 TI - Enhanced sensitized NIR luminescence from gold nanoparticles via energy transfer from surface-bound fluorophores. PMID- 17286407 TI - Synthesis and characterization of donor-acceptor chromophores for unidirectional electron transfer. AB - [reaction: see text] A series of electron-transfer chromophores containing a donor and acceptor linked by an alkyl spacer were synthesized, and their electronic spectra were investigated. By inclusion with amylose, the supramolecularly encapsulated chromophores exhibit enhanced fluorescence quenching with discrete distance dependence and acquire the ability to sustain self-assemblies of a densely packed supramolecular array on a SiOH/Si substrate. PMID- 17286408 TI - Exploiting nucleotidylyltransferases to prepare sugar nucleotides. AB - [reaction: see text] Enzymatic approaches to prepare sugar nucleotides are gaining in importance and offer several advantages over chemical synthesis including high yields and stereospecificity. We report the cloning, expression, and purification of two new wild-type thymidylyltransferases and observed catalysis with a wide variety of substrates. Significant product inhibition was not observed with the enzymes studied over a 24 h period, enabling the efficient preparation of 15 sugar nucleotides, clearly demonstrating the synthetic utility of these biocatalysts. PMID- 17286409 TI - A spirodiepoxide-based strategy to the A-B ring system of pectenotoxin 4. AB - [reaction: see text] A synthesis of a pectenotoxin 4 C1-C15 segment is reported. Suitable C1-C7 and C8-C15 segments were prepared, coupled, converted to I and the C3-hydroxy variant, and then cyclized. Key findings include the stereoselective conversion of the allene to the corresponding spirodiepoxide, oxidative cleavage of the p-methoxybenzyl ether, and cyclization of the spirodiepoxide to spiroketal II. PMID- 17286410 TI - Click chemistry in CuI-zeolites: the Huisgen [3 + 2]-cycloaddition. AB - [reaction: see text] CuI-exchanged solids based on zeolite materials were investigated for the first time as catalysts in organic synthesis. The catalytic potential of these materials was evaluated in the Huisgen [3 + 2]-cycloaddition. Five CuI-exchanged zeolites were examined and CuI-USY proved to be a novel and efficient heterogeneous ligand-free catalyst for this "click chemistry"-type transformation. PMID- 17286411 TI - Rhodamine-based Hg2+-selective chemodosimeter in aqueous solution: fluorescent OFF-ON. AB - [reaction: see text] N-(Rhodamine-6G)lactam-N'-phenylthiourea-ethylenediamine (1) was developed as a fluorescent and colorimetric chemodosimeter in aqueous solution with a broad pH span (5 approximately 10) and high selectivity toward Hg2+ but no significant response toward other competitive cations, such as Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Pb2+, Cd2+, Ca2+, Mg2+, K+, Na+, etc. The Hg2+-promoted ring opening of spirolactam of the rhodamine moiety induced cyclic guanylation of the thiourea moiety, which resulted in the dual chromo- and fluorogenic observation (OFF-ON). PMID- 17286413 TI - Utilization of restaurant waste oil as a precursor for sophorolipid production. AB - Approximately 100 billion liters of oil is generated per week as waste from restaurants around the country. Because of health, environmental, and economic factors, current methods of disposal are ineffective for disposal of the restaurant oil wastes. In this study we have investigated the ability of Candida bombicola to fermentatively transform the restaurant oil waste into glycolipids called sophorolipids. Batch and fed-batch studies were carried out using oil waste as the lipid feedstock in Erlenmeyer flasks and in a fermentor. Batch fermentation in a fermentor gave the highest yield of sophorolipids of 34 g L-1. Fermentation using oleic acid as control feedstock were also carried out. Batch fermentation in the fermentor using this pure fatty acid gave a highest yield of 42 g L-1. The difference in the sophorolipid yield was attributed to the fatty acid composition of restaurant oil waste. PMID- 17286412 TI - Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. AB - Dietary polyphenols have been associated with reduced risk of chronic diseases, but the precise molecular mechanisms of protection remain unclear. This work was aimed at studying the effect of (-)-epicatechin (EC) and chlorogenic acid (CGA) on the regulation of apoptotic and survival/proliferation pathways in a human hepatoma cell line (HepG2). EC or CGA treatment for 18 h had a slight effect on cell viability and decreased reactive oxygen species formation, and EC alone promoted cell proliferation, whereas CGA increased glutathione levels. Phenols neither induced the caspase cascade for apoptosis nor affected expression levels of Bcl-xL or Bax. A sustained activation of the major survival signals AKT/PI-3 kinase and ERK was shown in EC-treated cells, rather than in CGA-exposed cells. These data suggest that EC and CGA have no effect on apoptosis and enhance the intrinsic cellular tolerance against oxidative insults either by activating survival/proliferation pathways or by increasing antioxidant potential in HepG2. PMID- 17286414 TI - Transformation from ordered islands to holes in phase-separating P2VP/PS blend films by adding Triton X-100. AB - Our previous investigation showed that the ordered hexagonal island pattern in the phase-separating polymeric blend films of polystyrene and poly(2 vinylpyridine) (PS/P2VP) formed due to the convection effect by proper control of PS molecular weight, solvent evaporation rate, and the weight ratio of PS to P2VP. In this paper, we further illustrate that, by adding a proper amount of the surfactant Triton X-100 to the PS/P2VP toluene solution, the ordered hexagonal island pattern can be transformed to the ordered honeycomb pattern. The effects of the amount of Triton X-100 on the surface morphology evolution and the pattern transformation are discussed in terms of the collapse of Triton X-100, phase separation between Triton X-100/P2VP and PS, the interfacial interaction between Triton X-100/P2VP and the mica substrate, and the Benard-Marangoni convection. PMID- 17286415 TI - Adsorption of plasmid DNA to a natural organic matter-coated silica surface: kinetics, conformation, and reversibility. AB - A quartz crystal microbalance with dissipation (QCM-D) has been used to determine the adsorption rate of ampicillin-resistant linear and supercoiled plasmid DNA onto a silica surface coated with natural organic matter (NOM). The structure of the resulting adsorbed DNA layer was determined by analyzing the viscoelastic properties of the adsorbed DNA layers as they formed and were then exposed to solutions of different ionic composition. The QCM-D data were complemented by dynamic light scattering measurements of diffusion coefficients of the DNA molecules as a function of solution ionic composition. The obtained results suggest that electrostatic interactions control the adsorption and structural changes of the adsorbed plasmid DNA on the NOM-coated silica surface. The adsorption of DNA molecules to the NOM layer took place at moderately high monovalent (sodium) electrolyte concentrations. A sharp decrease in solution ionic strength did not result in the release of the adsorbed DNA, indicating that DNA adsorption on the NOM-coated silica surface is irreversible under the studied solution conditions. However, the decrease in electrolyte concentration influenced the structure of the adsorbed layer, causing the adsorbed DNA to adopt a less compact conformation. The linear and supercoiled DNA had similar adsorption rates, but the linear DNA formed a thicker and less compact adsorbed layer than the supercoiled DNA. PMID- 17286416 TI - Stability of 2-D colloidal particle aggregates held against flow stress in an ultrasound trap. AB - The formation of a two-dimensional aggregate of 25 microm latex particles in a 1.5 MHz ultrasound standing wave (USW) field and its disintegration in a flow were studied. The aggregate was held in the pressure node plane, which allowed continuous microscope observation and video recording of the processes. The trajectories and velocities of the particles approaching the formation site were analyzed by particle image velocimetry (PIV). Since the direct radiation force on the particles dominated the drag due to acoustic streaming, the acoustic pressure profile in the vicinity of the aggregate was quantifiable. The drag coefficients D(coef) for 2- to 485-particle aggregates were estimated from the balance of the drag force FD and the buoyancy-corrected gravitational force during sedimentation on termination of the ultrasound when the long axis of the aggregate was in the vertical plane. D(coef) were calculated from FD as proportional to the aggregate velocity. Experiments on particle detachment by flow (in-plane velocity measured by PIV) from horizontal aggregates suspended in deionized water and CaCl2 solution of different concentrations showed that the mechanical strength of the aggregates depended on the acoustic pressure amplitude P0 and ionic strength of the solution. In deionized water the flow velocity required to detach the first single particle from an aggregate increased from 1 mm s-1 at P0 = 0.6 MPa to 4.2 mm s-1 at P0 = 1.4 MPa. The balance of forces acting on particles in a USW trap is discussed. The magnitude of the shear stress employed ( approximately 0.05 Pa) and separation forces suggests that this technique can be applied to studying the mechanical responses of cell aggregates to hydrodynamic flow, where cell-cell interaction can be separated from the effects of solid substrata. PMID- 17286417 TI - Interactive adsorption behavior of NAD+ at a gold electrode surface. AB - The adsorption of an oxidized form of nicotinamide adenine dinucleotide, NAD+, on a polycrystalline gold electrode surface and the subsequent surface conformation of the molecule were investigated over a wide temperature and potential range, using electrochemical differential capacitance and PM-IRRAS techniques. The adsorption process was described by the Langmuir adsorption isotherm. The corresponding thermodynamic parameters were determined: the Gibbs energy, enthalpy, and entropy of adsorption. The large negative Gibbs energy of adsorption (-43 +/- 4 kJ mol-1 and -39 +/- 2 kJ mol-1 on a positively and negatively charged surface, respectively) confirms that the NAD+ adsorption process is highly spontaneous, while the large entropy gain (285 J K-1 mol-1 and 127 J K-1 mol-1 on a positively and negatively charged surface, respectively) was found to represent the adsorption driving force. It was demonstrated that the energetics of the adsorption process is surface-charge controlled, while its kinetics is both mass-transport and surface-charge controlled. A surface-charge dependent conformation model for the adsorbed NAD+ molecule is proposed. These findings suggest that the origin of the NAD+ reduction overpotential is related to the surface conformation of the adsorbed NAD+ molecule, rather than to the electrode Fermi level position. PMID- 17286418 TI - Adsorbed gels versus brushes: viscoelastic differences. AB - It is of fundamental importance to be able to easily distinguish between the viscoelastic properties of a molecular gel (noncovalent cross-linked three dimensional polymer structure) and a brush (polymer structure that emanates from a surface in three dimensions without cross-linking). This has relevance in biology and in designing surfaces with desired chemical and viscoelastic properties for nano and genomic technology applications. Agarose and thiol-tagged poly(ethylene glycol) were chosen as model systems, as they are known, on adsorption, to behave like a molecular gel and brush, respectively. Here, we focus on their viscoelastic differences using a quartz crystal microbalance with dissipation monitoring (QCM-D). Changes in resonance frequency and dissipation for three overtones using QCM-D were fitted with the Voigt viscoelastic model to calculate the shear viscosity and shear modulus for the adsorbed agarose gel and the PEG brush. At a surface coverage of 500 ng/cm2, the shear viscosities and shear moduli were 0.0025 +/- 0.0002 Pa-s and 2.0 +/- 0.17 x 105 Pa and 0.0010 +/- 0.0001 Pa-s and 5.0 +/- 0.3 x 104 Pa for the gel and brush, respectively. Thus, the adsorbed agarose gel layer was far more rigid than that of the covalently bound PEG brush due to its cross-linked network. Also, the diffusivity of agarose and PEG in solution was compared during adsorption onto a bare gold surface. The estimated value for the effective diffusivity of the PEG (without a thiol tag) and of the agarose gel was on the order of 10(-11) and 10(-15) m2/s, respectively. This low diffusivity for agarose supports the contention that it exists as a molecular gel with a H-bonded cross-linked network in aqueous solution. With the methods used here, it is relatively easy to distinguish the differences in viscoelastic properties between an adsorbed gel and brush. PMID- 17286420 TI - Colloidal complexes from poly(vinyl amine) and carboxymethyl cellulose mixtures. AB - The phase behaviors of polyelectrolyte complexes formed from dilute solutions of poly(vinyl amine) (PVAm) and carboxymethyl cellulose (CMC) were determined as a function of overall composition and pH. The phase diagram included regions with soluble complexes, colloidal complexes, and macroscopic precipitates. Colloidal complexes were stable when either polymer was in sufficient excess to give electrosteric stabilization. The polymer mixing ratios giving complexes with an isoelectric point of 7 could be predicted from a simple model using the degree of ionization vs pH data for PVAm and CMC. The model failed at extreme pH values because not all added polymer was incorporated into the complexes. At pH 7, essentially all the added polymer was incorporated into the colloidal complex or precipitate, as long as the mixing ratio was within +/-10% of charge stoichiometry. The interaction of PVAm and CMC at pH 7 was endothermic, supporting the generally accepted viewpoint that the interaction of oppositely charged polyelectrolytes is entropy-driven. Although the colloidal complexes had a broad particle size distribution, the average particle size was rather insensitive to mixing ratio. By contrast, complex size was sensitive to electrolyte concentration with no complex formation when the NaCl concentration was > or =2 M. PMID- 17286419 TI - Formation and activity of template-assembled receptor signaling complexes. AB - Problems in membrane biology require methods to recreate the interactions between receptors and cytoplasmic signaling proteins at the membrane surface. Here, unilamellar vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine and a nickel-chelating lipid were used as templates to direct the assembly of proteins from the Escherichia coli chemotaxis signaling pathway. The bacterial chemoreceptors are known to form clusters, which promote the binding of the adaptor protein (CheW) and the kinase (CheA). When CheA was incubated with vesicles, CheW, and a histidine-tagged cytoplasmic domain fragment of the aspartate chemoreceptor (CF), the kinase activity was stimulated approximately 300-fold. Activity and pull-down assays were used with dynamic light scattering and electron microscopy to characterize the protein-vesicle compositions that were correlated with the high levels of activity, which demonstrated that CF-CheW CheA complexes on the vesicle surface were the active entities. Assembly and stimulation occurred with vesicles of different sizes and CFs in different extents of glutamine substitution (in place of glutamate) at physiologically relevant sites. An exception was the combination of sonicated vesicles with the unsubstituted CF, which displayed lower CheA activity. The lower activity was attributed to the high curvature of the sonicated vesicles and a weaker tendency of the unsubstituted CF to self-assemble. Electron micrographs of the vesicle protein assemblies revealed that protein binding induced pronounced changes in vesicle shape, which was consistent with the introduction of positive curvature in the outer leaflet of the bilayer. Overall, vesicle-mediated template-directed assembly is shown to be an effective way to form functional complexes of membrane associated proteins and suggests that significant changes in membrane shape can be involved in the process of transmembrane signaling. PMID- 17286421 TI - RNA-mediated fluorescent Q-PbS nanoparticles. AB - RNA-mediated fluorescent PbS nanoparticles have been synthesized in the quantum confined region of a face-centered cubic phase. The binding of RNA to the surface of PbS nanoparticles has been exploited to tailor its size and to improve the stability and electronic properties. These particles display excitonic features and a relatively strong narrow emission band (fwhm 70 nm) at 675 nm with a broad excitation range extending from 330 to 620 nm. The manipulation of experimental conditions could control the relaxation dynamics of charge carriers in the illuminated particles. The multifunctionality of the RNA structure contributes to the observed electronic properties in a cooperative manner. Such biopolymeric nanostructures may find tremendous applications in the fabrication of solar cells, fluorescence imaging, and detection devices. PMID- 17286422 TI - Self-assembly of a hexagonal boron nitride nanomesh on Ru(0001). AB - Hexagonal boron nitride (h-BN) nanostructures were grown on Ru(0001), and are very similar to those previously reported on Rh(111). They show a highly regular 12 x 12 superstructure, comprising 2 nm wide apertures with a depth of about 0.1 nm. Valence band photoemission reveals two distinctly bonded h-BN species, and X ray photoelectron spectroscopy indicates an h-BN monolayer film. The functionality of the h-BN/Ru(0001) nanomesh is demonstrated by using this structure for the assembly of gold nanoclusters. PMID- 17286423 TI - Phase relations and binary clathrate hydrate formation in the system H2-THF-H2O. AB - Experimentally determined equilibrium phase relations are reported for the system H2-THF-H2O as a function of aqueous tetrahydrofuran (THF) concentration from 260 to 290 K at pressures up to 45 MPa. Data are consistent with the formation of cubic structure-II (CS-II) binary H2-THF clathrate hydrates with a stoichiometric THF-to-water ratio of 1:17, which can incorporate modest volumes of molecular hydrogen at elevated pressures. Direct compositional analyses of the clathrate phase, at both low (0.20 mol %) and stoichiometric (5.56 mol %) initial THF aqueous concentrations, are consistent with observed phase behavior, suggesting full occupancy of large hexakaidecahedral (51264) clathrate cavities by THF, coupled with largely complete (80-90%) filling of small dodecahedral (512) cages by single H2 molecules at pressures of >30 MPa, giving a clathrate formula of (H2) < or =2.THF.17H2O. Results should help to resolve the current controversy over binary H2-THF hydrate hydrogen contents; data confirm recent reports that suggest a maximum of approximately 1 mass % H2, this contradicting values of up to 4 mass % previously claimed for comparable conditions. PMID- 17286424 TI - Detection of single ion channel activity on a chip using tethered bilayer membranes. AB - Membrane-bound ion channels are promising biological receptors since they allow for the stochastic detection of analytes at high sensitivity. For stochastic sensing, it is necessary to measure the ion currents associated with single ion channel opening and closing events. However, this calls for stability, high reproducibility, and long lifetimes. A critical issue to overcome is the low stability of the ion channel environment, that is, the bilayer membrane. A promising technique to surmount this is to connect the lower part of the membrane to a surface forming a tethered bilayer membrane. By reconstituting the synthetic ion channel, gramicidin A, into a tethered bilayer as part of a microchip design, we have been able to record the activity of single ion channels. The observed activity was compared with that obtained by a conventional electrophysiology method, tip dipping, to confirm its authenticity. These findings allow for the construction of stable biosensors based on ion channels and provide a novel technique for the characterization of ion channel activity. PMID- 17286425 TI - Development of reagents for differential protein quantitation by subtractive parent (precursor) ion scanning. AB - We present a generic approach for quantitative differential proteomics that reduces data complexity in proteome analysis by automated selection of peptides for MS/MS analysis according to their isotope-labeling ratio. Isotopic reagents were developed that give products which fragment easily to generate a unique pair of signature ions. Using the ion-pair ratio, we show that it is possible to select only BSA peptides (with a 3:1 light heavy isotope ratio) for MS/MS when spiked in a whole yeast extract using Parent (precursor) Ion Quantitation Scanning (PIQS) for MS/MS. PMID- 17286426 TI - Organization and dynamics of NBD-labeled lipids in membranes analyzed by fluorescence recovery after photobleaching. AB - Lateral diffusion of membrane constituents plays an important role in membrane organization and represents a central theme in current models describing the structure and function of biological membranes. Fluorescence recovery after photobleaching (FRAP) is a widely used approach that provides information regarding dynamic properties and spatial distribution of membrane constituents. On the basis of the unique concentration-dependent fluorescence emission properties of a fluorescently labeled cholesterol analogue modified at the tail region, 25-[N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-methyl]amino]-27 norcholesterol (25-NBD-cholesterol), we have previously shown that it exhibits local organization even at very low concentrations in membranes. In this paper, we address aspects regarding the molecular size and dynamics of such an organized assembly of 25-NBD-cholesterol by monitoring its lateral diffusion characteristics using FRAP. To obtain a comprehensive understanding of the organization and dynamics of 25-NBD-cholesterol in the membrane, we compare its diffusion properties to that of a fluorescent phospholipid analogue 1,2 dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-(1,3-benzoxadiazol-4 yl)) (NBD-PE). Our results indicate significant differences in the membrane dynamics of these NBD-labeled lipids. Importantly, on the basis of a novel wavelength-selective FRAP approach, our results show that the organization of 25 NBD-cholesterol is heterogeneous, with the presence of fast- and slow-diffusing species which could correspond to predominant populations of monomers and dimers of 25-NBD-cholesterol. The potential application of the wavelength-selective FRAP approach to monitor the organization and dynamics of molecules in membranes therefore represents an exciting possibility. PMID- 17286427 TI - Directed assembly of binary monolayers with a high protein affinity: infrared reflection absorption spectroscopy (IRRAS) and surface plasmon resonance (SPR). AB - Infrared reflection absorption spectroscopy (IRRAS) and surface plasmon resonance (SPR) techniques have been employed to investigate human serum albumin (HSA) binding to binary monolayers of zwitterionic dipalmitoylphosphatidylcholine (DPPC) and cationic dioctadecyldimethylammonium bromide (DOMA). At the air-water interface, the favorable electrostatic interaction between DPPC and DOMA leads to a dense chain packing. The tilt angle of the hydrocarbon chains decreases with increasing mole fraction of DOMA (X(DOMA)) in the monolayers at the surface pressure 30 mN/m: DPPC ( approximately 30 degrees ), X(DOMA) = 0.1 ( approximately 15 degrees ), and X(DOMA) = 0.3 ( approximately 0 degrees ). Negligible protein binding to the DPPC monolayer is observed in contrast to a significant binding to the binary monolayers. After HSA binding, the hydrocarbon chains at X(DOMA) = 0.1 undergo an increase in tilt angle from 15 degrees to 25 approximately 30 degrees , and the chains at X(DOMA) = 0.3 remain almost unchanged. The two components in the monolayers deliver through lateral reorganization, induced by the protein in the subphase, to form multiple interaction sites favorable for protein binding. The surfaces with a high protein affinity are created through the directed assembly of binary monolayers for use in biosensing. PMID- 17286428 TI - New insights into the reaction mechanism catalyzed by the glutamate racemase enzyme: pH titration curves and classical molecular dynamics simulations. AB - The mechanism of the reactions catalyzed by the pyridoxal-phosphate-independent amino acid racemases and epimerases faces the difficult task of deprotonating a relatively low acidicity proton, the amino acid's alpha-hydrogen, with a relatively poor base, a cysteine. In this work, we propose a mechanism for one of these enzymes, glutamate racemase (MurI), about which many controversies exist, and the roles that its active site residues may play. The titration curves and the pK1/2 values of all of the ionizable residues for different structures leading from reactants to products have been analyzed. From these results a concerted mechanism has been proposed in which the Cys70 residue would deprotonate the alpha-hydrogen of the substrate while, at the same time, being deprotonated by the Asp7 residue. To study the consistency of this mechanism classical molecular dynamics (MD) simulations have been carried out along with pK1/2 calculations on the MD-generated structures. PMID- 17286430 TI - Special issue in honor of Professor Kenneth L. Rinehart. PMID- 17286429 TI - Search for cell motility and angiogenesis inhibitors with potential anticancer activity: beauvericin and other constituents of two endophytic strains of Fusarium oxysporum. AB - Wound-healing assay-guided fractionation of an EtOAc extract of the fungal strain Fusarium oxysporum EPH2RAA endophytic in Ephedra fasciculata afforded beauvericin (1), (-)-oxysporidinone (2), and two new N-methyl-2-pyridones, (-)-4,6' anhydrooxysporidinone (3) and (-)-6-deoxyoxysporidinone (4). Beauvericin (1) inhibited migration of the metastatic prostate cancer (PC-3M) and breast cancer (MDA-MB-231) cells and showed antiangiogenic activity in HUVEC-2 cells at sublethal concentrations. Cytotoxicity-guided fractionation of an EtOAc extract of F. oxysporum strain CECIS occurring in Cylindropuntia echinocarpus afforded rhodolamprometrin (5), bikaverin (6), and the new natural product 6 deoxybikaverin (7). All compounds were evaluated for cytotoxicity in a panel of four sentinel cancer cell lines, NCI-H460 (non-small-cell lung), MIA Pa Ca-2 (pancreatic), MCF-7 (breast), and SF-268 (CNS glioma), and only beauvericin (1) and bikaverin (6) were active, with 1 and 6 showing selective toxicity toward NCI H460 and MIA Pa Ca-2, respectively. Interestingly, 6-deoxybikaverin (7) was completely devoid of activity, suggesting the requirement of the C-6 hydroxy group of bikaverin for its cytotoxic activity. PMID- 17286431 TI - Cinnamacrins A-C, cinnafragrin D, and cytostatic metabolites with alpha glucosidase inhibitory activity from Cinnamosma macrocarpa. AB - Two new monomeric and two new dimeric drimane sesquiterpenes, cinnamacrins A-C (1 3) and cinnafragrin D (4), along with bemadienolide (5), capsicodendrin (6), cinnamodial (7), cinnamolide (8), isopolygodial (9), and delta-tocotrienol (10), were isolated from Cinnamosma macrocarpa. The structures of the new compounds were determined by physical, chemical, and spectroscopic evidence. Capsicodendrin (6) and/or cinnamodial (7) are the major compounds in C. fragrans and C. macrocarpa, which are both widely used in Malagasy traditional medicine. The cytostatic activity as well as alpha-glucosidase inhibition and antiviral activities of the major constituents 6 and 7 and the compounds previously isolated from C. fragrans were evaluated. PMID- 17286432 TI - On the use of 3,5-O-benzylidene and 3,5-O-(di-tert-butylsilylene)-2-O benzylarabinothiofuranosides and their sulfoxides as glycosyl donors for the synthesis of beta-arabinofuranosides: importance of the activation method. AB - A 2-O-benzyl-3,5-O-benzylidene-alpha-d-thioarabinofuranoside was obtained by reaction of the corresponding diol with alpha,alpha-dibromotoluene under basic conditions. On activation with 1-benzenesulfinyl piperidine, or diphenyl sulfoxide, and trifluoromethanesulfonic anhydride in dichloromethane at -55 degrees C, reaction with glycosyl acceptors affords anomeric mixtures with little or no selectivity. The analogous 2-O-benzyl-3,5-O-(di-tert-butylsilylene)-alpha-d thioarabinofuranoside also showed no significant selectivity under the 1 benzenesulfinyl piperidine or diphenyl sulfoxide conditions. With N iodosuccinimide and silver trifluoromethanesulfonate the silylene acetal showed moderate to high beta-selectivity, independent of the configuration of the starting thioglycoside. High beta-selectivity was also obtained with a 2-O-benzyl 3,5-O-(di-tert-butylsilylene)-alpha-arabinofuranosyl sulfoxide donor on activation with trifluoromethanesulfonic anhydride. The high beta-selectivities obtained by the N-iodosuccinimide/silver trifluoromethanesulfonate and sulfoxide methods are consistent with a common intermediate, most likely to be the oxacarbenium ion. The poor selectivity observed on activation of the thioglycosides with the 1-benzenesulfinyl piperidine, or diphenyl sulfoxide, and trifluoromethanesulfonic anhydride methods appears to be the result of the formation of a complex mixture of glycosyl donors, as determined by low temperature NMR work. PMID- 17286433 TI - Carbonyl allenylation/free radical cyclization sequence as a new regio- and stereocontrolled access to bi- and tricyclic beta-lactams. AB - A novel approach to racemic and enantiopure nonconventional fused bi- and tricyclic beta-lactams has been developed by using regio- and stereocontrolled intramolecular free radical reactions in monocyclic 2-azetidinone-tethered allenynes and haloallenes. The access to allene cyclization precursors was achieved by metal-mediated carbonyl allenylation of appropriately substituted 4 oxoazetidine-2-carbaldehydes in an aqueous environment. The tin-promoted radical cyclizations of allene-beta-lactams are totally regioselective for the central allenic carbon, providing bi- and tricyclic beta-lactams containing a seven membered ring. PMID- 17286434 TI - Efficient syntheses of a series of trehalose dimycolate (TDM)/trehalose dicorynomycolate (TDCM) analogues and their interleukin-6 level enhancement activity in mice sera. AB - We found an IL-6 level-enhancing compound during our synthetic study of trehalose 6,6'-dimycolate (1, TDM, formerly called cord factor) analogues. TDM is a glycolipid distributed in the cell wall of Mycobacterium tuberculosis and shows significant antitumor activity based on an immunoadjuvant activity. However, due to its significant toxicity, TDM is not yet applicable for practical use. In 1993, Datta and Takayama reported the purification of trehalose-6,6' dicorynomycolate (2c, TDCM) from Corynebacterium spp. We have previously reported the synthesis of four diastereomeric TDCMs and showed that the synthetic (2R,3R,2'R,3'R)-TDCM (2c, hereafter abbreviated RRRR-TDCM-C14) is identical to natural TDCM; we also demonstrated that 2c and SSSS-TDCM-C14 (3c) showed significant antitumor activity as well as inhibitory activity in experimental lung metastasis based on the immunoadjuvant activity. Furthermore, we found that the significant lethal toxicity in mice by TDM (1) was no longer observed with the shorter-chain analogues of TDCMs. Therefore, we have elucidated that the 2,3 antistereochemistry (RR or SS) of the fatty acid residue is promising for biological activities. The chain length of the fatty acid residue should also be important for the biological activity, and thus, we designed a general synthetic procedure for trehalose diesters with 2,3-antistereochemistry and a series of chain lengths by using Noyori's asymmetric reduction of beta,beta-ketoesters followed by antiselective alkylation according to Frater to give beta,beta hydroxy alcohols as the key steps. Thus, we prepared trehalose diesters (TDCM) 2a d, 3a-d, and 4a-d as well as monoesters (TMCM) 5a-d and 6a-d. Immunological activities of TDCMs and TMCMs were evaluated by determining IL-6 level enhancement in mouse serum, and we found that RRRR-TDCM-C14 (2c) and RRSS-TDCM C14 (4c) showed significant IL-6 level enhancement activities. PMID- 17286435 TI - Chiral helicenoid diarylethene with large change in specific optical rotation by photochromism. AB - A diarylethene possessing one [4]thiaheterohelicene and one benzothiophene, the latter with a chiral methoxymethoxyethyl group on its C-3 position, was proved to work as a switch of specific optical rotation at a wavelength at which both colored and colorless forms have no absorption in solution. The difference of the specific optical rotation was 1300 degrees between the open form and the photostationary state. The specific optical rotation of one of the isolated optically active major colored forms was -4680 degrees. The conversion to the colored form was 64%, and the diastereomeric excess of photocyclization was 47%. PMID- 17286436 TI - Chiral helicenoid diarylethene with highly diastereoselective photocyclization. AB - A novel photochromic helicenoid diarylethene (R)-1-[1-(1-methoxymethoxyethyl)-2 naphtho[2,1-b]thienyl]-2-(2,4,5-trimethyl-3-thienyl)hexafluorocyclopentene was synthesized enantioselectively. It showed highly diastereoselective photocyclization (90% de) and a large change (950 degrees) in the specific optical rotation value at 633 nm upon UV light irradiation in ethyl acetate. PMID- 17286437 TI - Synthesis of 1,3,5-tricarbonyl derivatives by condensation of 1,3-bis(silyl enol ethers) with acid chlorides. AB - A variety of 1,3,5-tricarbonyl derivatives were prepared by reaction of 1,3 bis(silyl enol ethers) with acid chlorides under mild conditions. This includes reactions of both aromatic and aliphatic acid chlorides and bis(acid chlorides). The yields vary depending on the type of acid chloride employed. PMID- 17286438 TI - Nitrile biotransformations for the efficient synthesis of highly enantiopure 1 arylaziridine-2-carboxylic acid derivatives and their stereoselective ring opening reactions. AB - Catalyzed by the Rhodococcus erythropolis AJ270 whole cell catalyst under very mild conditions, biotransformations of racemic 1-arylaziridine-2-carbonitriles proceeded efficiently and enantioselectively to produce highly enantiopure S-1 arylaziridine-2-carboxamides and R-1-arylaziridine-2-carboxylic acids in excellent yields. Although the nitrile hydratase exhibits no selectivity against all nitrile substrates, the amidase is highly R-enantioselective towards 1 arylaziridine-2-carboxamides. When treated with benzyl bromide, 1-phenylaziridine 2S-carboxamide underwent a highly regioselective and enantiospecific ring-opening reaction to afford an almost quantitative yield of R-beta-[(benzyl)phenylamino] alpha-bromopropanamide (C-2 attack) and R-alpha-[(benzyl)phenylamino]-beta bromopropanamide (C-3 attack) in a 10.5:1 ratio. Further treatment of the resulting ring-opening products with an N-nucleophilic reagent such as amine and azide led to, through most probably the aziridinium intermediate, the formation of S-alpha-substituted-beta-[(benzyl)phenylamino]propanamides in good chemical yields with high enantiomeric purity. PMID- 17286439 TI - General strategy for the synthesis of B1 phytoprostanes, dinor isoprostanes, and analogs. AB - The synthesis of the phytoprostane B1 types I and II is achieved in high overall yield (35-53%) by only two principal transformations starting from 1,3 cyclopentanedione. The first side chain is attached via O-acylation of the 1,3 dione followed by rearrangement and reduction to give the 2-alkyl-1,3-diones 4a c. After conversion into the corresponding vinylic iodides 5a-c, the second side chain is introduced by transition metal catalysis following Heck- or Sonogashira type protocols. The whole spectrum of the phytoprostane B1 types I, II, and the dinor isoprostane B1 type III and some structural analogs are rapidly accessible along the same general protocol. PMID- 17286440 TI - CuI-catalyzed suzuki-miyaura and sonogashira cross-coupling reactions using DABCO as ligand. AB - In the presence of TBAB, CuI-catalyzed Suzuki-Miyaura cross-coupling of vinyl halides and aryl halides with arylboronic acids was conducted smoothly to afford the corresponding diarylethenes and polyaryls in moderate to good yields using DABCO (1,4-diazabicyclo[2.2.2]octane) as the ligand. We also found that the inexpensive CuI/DABCO catalytic system was effective for Sonogashira cross couplings of aryl halides and vinyl halides. A variety of aryl halides and vinyl halides including activated aryl chlorides underwent the coupling with terminal alkynes in moderate to excellent yields. PMID- 17286442 TI - How to compute isomerization energies of organic molecules with quantum chemical methods. AB - The reaction energies for 34 typical organic isomerizations including oxygen and nitrogen heteroatoms are investigated with modern quantum chemical methods that have the perspective of also being applicable to large systems. The experimental reaction enthalpies are corrected for vibrational and thermal effects, and the thus derived "experimental" reaction energies are compared to corresponding theoretical data. A series of standard AO basis sets in combination with second order perturbation theory (MP2, SCS-MP2), conventional density functionals (e.g., PBE, TPSS, B3-LYP, MPW1K, BMK), and new perturbative functionals (B2-PLYP, mPW2 PLYP) are tested. In three cases, obvious errors of the experimental values could be detected, and accurate coupled-cluster [CCSD(T)] reference values have been used instead. It is found that only triple-zeta quality AO basis sets provide results close enough to the basis set limit and that sets like the popular 6 31G(d) should be avoided in accurate work. Augmentation of small basis sets with diffuse functions has a notable effect in B3-LYP calculations that is attributed to intramolecular basis set superposition error and covers basic deficiencies of the functional. The new methods based on perturbation theory (SCS-MP2, X2-PLYP) are found to be clearly superior to many other approaches; that is, they provide mean absolute deviations of less than 1.2 kcal mol-1 and only a few (<10%) outliers. The best performance in the group of conventional functionals is found for the highly parametrized BMK hybrid meta-GGA. Contrary to accepted opinion, hybrid density functionals offer no real advantage over simple GGAs. For reasonably large AO basis sets, results of poor quality are obtained with the popular B3-LYP functional that cannot be recommended for thermochemical applications in organic chemistry. The results of this study are complementary to often used benchmarks based on atomization energies and should guide chemists in their search for accurate and efficient computational thermochemistry methods. PMID- 17286441 TI - 1,1-dioxonaphtho[1,2-b]thiophene-2-methyloxycarbonyl (alpha-Nsmoc) and 3,3 dioxonaphtho[2,1-b]thiophene-2-methyloxycarbonyl (beta-Nsmoc) amino-protecting groups. AB - Of the three theoretically possible, Bsmoc-related, naphthothiophene sulfone based amino-protecting groups, the two most readily available derivatives, the alpha- and beta-Nsmoc analogues, have been examined as substitutes for the Bsmoc residue in cases where the latter lead to oily protected amino acids or amino acid fluorides. All of the naphtho systems gave easily handled solid amino acid derivatives. The intermediate sulfone alcohol 11 used as the key reagent for introduction of the alpha-Nsmoc protecting group was readily made from alpha tetralone (Scheme 1). The corresponding beta-analogue 17 was made similarly on a small scale, but due to the high cost of beta-tetralone, an alternate route involving reaction of rhodanine with alpha-naphthaldehyde was used for large scale work (Scheme 2). All proteinogenic amino acids were converted to their alpha- and beta-Nsmoc derivatives. Deblocking studies showed that the reactivity toward deblocking by piperidine followed the order alpha-Nsmoc > Bsmoc > beta Nsmoc. 1H NMR experiments showed that deblocking of the two new systems was mechanistically similar to that previously established for the Bsmoc derivative in that the reaction is initiated by Michael addition to the beta-carbon atom of the alpha,beta-unsaturated sulfone system. Application of alpha- and beta-Nsmoc amino acids to the solid-phase synthesis of two model peptides was examined. An advantage of the alpha-Nsmoc system over the long-known Bsmoc system proved to be the milder conditions needed for the deblocking step relative to the Bsmoc case, which is itself more readily deblocked than the classic Fmoc analogue. PMID- 17286443 TI - Interaction of halide and carboxylate ions with 4,5-diacetamidoacridine-9(10H) one: thermodynamics of association and deprotonation events. AB - 4,5-Diacetamidoacridine-9(10H)-one was prepared, and its interactions with halide and benzoate anions were studied using a combination of NMR, fluorescence, and isothermal titration calorimetry experiments. Whereas chloride and bromide exhibited simple association, both fluoride and benzoate exhibited initial entropy-driven association followed by an enthalpically favorable deprotonation of the receptor by a second equivalent of the anion. PMID- 17286444 TI - Crotylation versus propargylation: two routes for the synthesis of the C13-C18 fragment of the antibiotic branimycin. AB - The C13-C18 fragment 3 of the novel antibiotic branimycin was prepared along two highly stereocontrolled routes. The first one uses a standard Roush crotylation protocol, whereas the second one proceeds via an allenyl silane propargylation with unexpected stereochemical consequences, which are discussed in detail. PMID- 17286445 TI - Array-based split-pool combinatorial screening of potential catalysts. AB - A new method for screening split-pool combinatorial libraries for catalytic activity is described. Site-selective detection of catalytic activity for solution-based reactions was made possible without cofunctionalizing beads or adding diffusion-limiting matrixes. This was done by spatially separating resin bound catalysts on an adhesive array on a microscope slide and introducing the reacting liquid to the top of the slide. Convective mixing and evaporation was controlled using a cover slide and imaging both the formation of products within active beads and the diffusion of products out of the beads. Colored reaction products and pH-sensitive indicators were used to visually detect catalytically active beads in the presence of inactive ones. Quantitative analyses of the images support the assumption that color intensities can be used to assess the quality of hits from a combinatorial screen. The Knoevenagel condensation reaction catalysis as well as esterase screening using methyl red were used to validate the approach. Using the esterase data, it was shown that some information on activity could also be extracted from the colored plume surrounding individual beads although the precision is not as good as that from direct measurement of absorbance through the bead. It was also found that the distribution of products within a single bead can also be gleaned from the absorbance data for different-sized beads. PMID- 17286447 TI - The BiolAD-DB system : an informatics system for clinical and genetic data. AB - The Biology of Addictive Diseases-Database (BiolAD-DB) system is a research bioinformatics system for archiving, analyzing, and processing of complex clinical and genetic data. The database schema employs design principles for handling complex clinical information, such as response items in genetic questionnaires. Data access and validation is provided by the BiolAD-DB client application, which features a data validation engine tightly coupled to a graphical user interface. Data integrity is provided by the password-protected BiolAD-DB SQL compliant server and database. BiolAD-DB tools further provide functionalities for generating customized reports and views. The BiolAD-DB system schema, client, and installation instructions are freely available at http://www.rockefeller.edu/biolad-db/. PMID- 17286448 TI - Identification of leukemia-specific fusion gene transcripts with a novel oligonucleotide array. AB - BACKGROUND: Identification of specific chromosomal translocations is essential for the diagnosis and prognosis of leukemia. In this study, we employ DNA microarray technology to detect chromosomal aberrations in patients with chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), as well as in leukemic cell lines. METHODS: Reverse transcription using a random 9-mer primer was performed with total RNA from patients and leukemic cells lines. Multiplex PCR reactions using four groups of primer sets were then performed for amplification of cDNA from reverse-transcribed total RNA samples. Normal and fusion sequences were distinguished by hybridization of the amplified cDNA to a selective oligonucleotide array (SOA) containing 20-30mer synthetic probes. A total of 23 sets of oligomers were fabricated on glass slides for the detection of normal and fusion genes, as follows: BCR/ABL, AML/EAP, AML/ETO, AML/MDS, PML/RARA, NUMA1/RARA, PLZF/RARA, and CBFB/MYH. RESULTS: Gene translocation in leukemia was effectively identified with the SOA containing various leukemia-specific fusion and normal control sequences. Leukemic fusion sequences from patients and cell lines hybridized specifically to their complementary probes. The probe sets differing by approximately 50% at their 5' or 3' ends could distinguish between normal and fusion sequences. The entire process of detection was completed within 8 hours using the SOA method. CONCLUSIONS: Probe sets on SOA can effectively discriminate between leukemia-specific fusion and normal sequences with a chip hybridization procedure. The oligonucleotide array presents several advantages in identifying leukemic gene translocations, such as multiplex screening, relatively low cost, and speed. PMID- 17286446 TI - A generic research paradigm for identification and validation of early molecular diagnostics and new therapeutics in common disorders. AB - Genetically complex disorders continue to confound investigators because of their many underlying factors, both genetic and environmental. In order to tease apart the heritable from the non-heritable contributions to disease, clinicians are relying on researchers in the rapidly expanding fields of high-throughput genomics to identify surrogate clinical endpoints, called biomarkers, that provide a measure of the probability that an individual will succumb to the disease in question. The goals of current biomedical research into complex disorders are to identify and utilize these biomarkers, not only for early detection, but also for personalized treatment with knowledge-guided therapeutics. As the identification of these biomarkers is basically a problem of discovery, we discuss new insights into biomarker detection utilizing the most current genomic technologies available. Additionally, we present here a generic paradigm for the validation of such molecular diagnostics as well as new treatment modalities for complex and increasingly common diseases. Lastly, we delve into the ways genomic biomarkers might be implemented in a clinical setting to allow the subsequent application of targeted therapeutics, which can help the ever expanding groups of individuals experiencing these insidious diseases. PMID- 17286450 TI - RB1 germ-line deletions in Argentine retinoblastoma patients. AB - BACKGROUND: Retinoblastoma (RB) is a malignant tumor originating in the retinal cell precursors and can be presented as a unilateral or bilateral form in childhood (one or both eyes affected). Development of this tumor is caused by mutations in the RB1 gene on chromosome 13q14; the first mutation may occur in the germ line (hereditary RB) or in somatic cells (non-hereditary RB). The hereditary form of RB is transmitted with a high penetrance to offspring (90%). Because early diagnosis is necessary for implementing effective treatment and preserving vision, it is important to identify the mutations in the affected family. AIM: The aim of this study was to identify large and small RB1 germ-line mutations and to correlate them with the RB phenotype. METHODS: Constitutional RB1 gene gross deletions were studied in 40 patients with bilateral or unilateral familial RB by a segregation assay of four intragenic polymorphisms located in introns 1, 4, 17, and 20 of the RB1 gene, along with fluorescence in situ hibridization (FISH) analysis. Small mutations were ascertained in a subgroup of ten patients by heteroduplex/sequence analysis of RB1-exons. RESULTS: In the course of our study, we have found three large deletions, which probably represent whole gene deletions, and two small deletions of 1bp in length. One large deletion was found in a family with several members affected. This represents a rare case of familial RB, which is usually caused by small mutations. Phenotype analysis of the family revealed a low penetrance inheritance, with an 'affected eyes : number of mutation-carriers' ratio of approximately 1.0, whereas this ratio in families with small loss-of-function mutations is 1.5-2.0. CONCLUSIONS: Our results emphasize the usefulness of a combined methodology that includes segregation of polymorphisms, FISH, and heteroduplex/sequence analyses for detection of gross and small DNA rearrangements in familial and sporadic RB. Identification of mutations in sporadic cases is important for risk-assessment in patients' relatives. The degree of penetrance in the inheritance of RB not only depends on the occurrence of the second mutation in the RB1 gene but also on the extent of inactivation of the first mutation. PMID- 17286449 TI - Diagnostic impact of molecular lineage analysis on paraffin-embedded tissue in hematolymphoid neoplasia reclassified by current WHO criteria. AB - BACKGROUND AND OBJECTIVE: By current WHO criteria, most - though not all - cases of hematolymphoid neoplasm can be diagnosed immunomorphologically, diminishing the role of molecular tests for lymphoid antigen receptor clonality in lymphoma diagnosis. Hence, our objective was to glean immunomorphological and molecular correlates from hematolymphoid neoplasms that had remained unresolvable without diagnostic molecular input. METHODS: Thirty-five such cases were reviewed histologically and with standard immunoperoxidases. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNAs (EBER) was performed on selected cases. PCR amplification of genes encoding T-cell receptors (TcR) and immunoglobulin heavy chains (IgH) [TR and IGH genes, respectively] was performed on whole tissue in all cases, and on microdissected cells in two cases. RESULTS: Twenty-five cases (71%) requiring diagnostic molecular genotyping had some form of peripheral T cell lymphoma (PTCL). Twenty (80%) of these were complicated by a proliferation of B-lineage cells, either within the same tissue ('syntopic') as large B cells (LBC) or Reed-Sternberg (RS)-like cells (17 cases), florid lymphoid hyperplasia (two cases, one also with syntopic LBC) or monotypic plasma cells (one case), or at a separate ('metatopic') site as a B-cell lymphoma (two cases, one of which also had syntopic LBC) or Hodgkin lymphoma (HL; one case, also showing syntopic LBC). Fifteen (75%) of these 20 PTCLs with B-lineage proliferation yielded monoclonal TR gene rearrangements, and only two (10%) showed IGH monoclonality, which was transient in one case. Three (18%) of the PTCLs with LBC had originally been misinterpreted as some form of HL. Conversely, of the remaining cases, three of four (75%) that had been diagnosed initially as some form of large cell non-HL (NHL), including two of three that were called 'anaplastic', had to be revised to grade II/syncytial nodular sclerosing (NS) HL, yielding polyclonal TcRgamma gene (TRG) rearrangements, with one case, in addition, disclosing a biallelic clonal IGH gene rearrangement that excluded anaplastic large cell lymphoma. DISCUSSION/CONCLUSION: Paradoxically, monoclonality of TR rather than IGH gene rearrangement may more often be detectable in a predominantly dispersed ('hodgkinoid'), large B-lineage cell proliferation, consistent with release from immune regulation in the milieu of impaired immunosurveillance within a PTCL. This is compounded by the difficulty in ascertaining clonal IGH gene rearrangements resulting from (1) poor consensus primer hybridization due to somatic hypermutations, and (2) 'dilution' in a T-cell-rich milieu. These same difficulties also account for the long-elusive identification of the RS cell lineage. Conversely, anaplastic lymphoma, which is of non-B lineage, may be mimicked by NSHL, which is of B lineage. PMID- 17286452 TI - The simplest all-nitrogen ring: photolytically filling the cyclic-N3 well. AB - We report evidence that cyclic-N(3) is exclusively produced in the 157-nm photolysis of ClN(3). Photoproduct translational energy measurements reveal a single-peaked distribution for an N(3)-formation channel with maximum and minimum translational energies matching the theoretically predicted minimum and maximum binding energies of cyclic-N(3), respectively. The absence of linear-N(3) greatly simplifies the data analysis. The zero-Kelvin heat of formation of cyclic-N(3) is derived experimentally (142+/-3.5 kcal/mol) and is in excellent agreement with the best existing determinations from other studies. PMID- 17286451 TI - Retinoblastoma in India : microsatellite analysis and its application in genetic counseling. AB - OBJECTIVES: This study was conducted with two objectives. The first was to estimate the frequency of loss of heterozygosity (LOH) of the RB1 gene as a mechanism in disease causation in tumors of patients from India. The second objective was to employ RB1 molecular deletion and microsatellite-based linkage analysis as laboratory tools, while counseling families with a history of retinoblastoma (RB). METHODS: DNA was extracted from peripheral blood and tumors of 54 RB patients and their relatives. Eight fluorescent microsatellite markers, both intragenic and flanking the RB1 gene, were used. After PCR amplification, samples were run on an ABI PRISM 310 genetic analyzer for LOH, deletion detection, and haplotype generation. RESULTS: LOH was found in conjunction with tumor formation in 72.9% of RB patients (39/54 patients; p=0.001; 95% CI 0.6028, 0.8417); however, we could not associate various other clinical parameters of RB patients with the presence or absence of RB1 LOH. Seven germline deletions (13% of RB patients) were identified, and the maternal allele was more frequently lost (p=0.01). A disease co-segregating haplotype was detected in two hereditary autosomal dominant cases. CONCLUSION: LOH of the RB1 gene could play an important role in tumor formation. Large deletions involving RB1 were observed, and a disease co-segregating haplotype was used for indirect genetic testing. This is the first report from India where molecular testing has been applied for RB families in conjunction with genetic counseling. In tertiary ophthalmic practice in India, there is an emerging trend towards the application of genetical knowledge in clinical practice. PMID- 17286453 TI - Classical treatment of molecular collisions: striking improvement of the description of recoil energy distributions using Gaussian weighted trajectories. AB - The Gaussian weighting (GW) procedure, recently used in the classical treatment of molecular collisions, is a practical way of taking into account quantization of product vibrational actions. The goal of this brief communication is to show that the GW procedure may drastically improve the predictions of the recoil energy distribution between final fragments, an observable frequently measured in molecular beam experiments. PMID- 17286454 TI - Differential scattering cross-sections for CN A2Pi+Ar. AB - We present the first results from a novel experimental approach to the measurement of state-to-state differential scattering cross-sections for inelastic scattering of electronically excited CN A(2)Pi with Ar. Photodissociation of ICN with linearly polarized 266 nm radiation generates CN X(2)Sigma(+) (upsilon(")=0,J(")) with a near mono-energetic speed distribution and large anisotropy. Saturated optical pumping of the nascent CN X(2)Sigma(+) transfers this speed distribution without distortion to selected rotational quantum states of the A(2)Pi (upsilon(')=4) level. The products of rotational energy transfer within the A(2)Pi (upsilon(')=4) level into the J(')=0.5, F(2), f, state are probed using frequency modulated stimulated emission spectroscopy on the A-X (4,2) band with a single frequency external cavity tunable diode laser. Doppler profiles of transitions from individual rotational, spin-orbit and lambda doublet specific levels are acquired for different geometrical arrangements of photolysis polarization and probe propagation directions. The resulting Doppler profiles, which for this J(')=0.5 state cannot display a rotational angular momentum alignment, are combined to yield composite Doppler profiles depending on speed and translational anisotropy, which are analyzed to determine fully state to-state resolved differential scattering cross-sections. PMID- 17286455 TI - Geometry of phenylene motion in polycarbonate from NMR spectroscopy and neutron scattering. AB - In view of the importance of molecular dynamics in condensed matter both time scale and geometry of such processes should be determined experimentally. Whereas many techniques are available for the former, only NMR spectroscopy and neutron scattering can provide detailed information on the latter. Because of the different time scales of the dynamics, which the two techniques can detect best, direct comparisons of probing the geometry of the dynamics in the same system are scarce. Here we present such a comparison for the complex rotational motion of the phenylene groups in amorphous polycarbonate based on published (2)H NMR and newly recorded (13)C NMR data covering a wide temperature range, and recent quasielastic neutron scattering (QENS) data. We show that the results of the two techniques are in remarkable agreement, provided the data are consistently analyzed. No evidence is found for additional motions characterized by 90 degrees flips recently deduced from QENS data alone. Instead, the phenylene motion in the glassy state displays a broad heterogeneous distribution of rotational angles, about 80 degrees in width, centered at a flip angle of 180 degrees , which stays essentially constant over a wide temperature range. Thus, the phenylene motion that can consistently be observed in NMR and neutron scattering experiments is sensitive to the local packing. PMID- 17286456 TI - Stochastic thermodynamics of chemical reaction networks. AB - For chemical reaction networks in a dilute solution described by a master equation, the authors define energy and entropy on a stochastic trajectory and develop a consistent nonequilibrium thermodynamic description along a single stochastic trajectory of reaction events. A first-law like energy balance relates internal energy, applied (chemical) work, and dissipated heat for every single reaction. Entropy production along a single trajectory involves a sum over changes in the entropy of the network itself and the entropy of the medium. The latter is given by the exchanged heat identified through the first law. Total entropy production is constrained by an integral fluctuation theorem for networks arbitrarily driven by time-dependent rates and a detailed fluctuation theorem for networks in the steady state. Further exact relations such as a generalized Jarzynski relation and a generalized Clausius inequality are discussed. The authors illustrate these results for a three-species cyclic reaction network which exhibits nonequilibrium steady states as well as transitions between different steady states. PMID- 17286457 TI - Quantum similarity study of atomic density functions: insights from information theory and the role of relativistic effects. AB - A novel quantum similarity measure (QSM) is constructed based on concepts from information theory. In an application of QSM to atoms, the new QSM and its corresponding quantum similarity index (QSI) are evaluated throughout the periodic table, using the atomic electron densities and shape functions calculated in the Hartree-Fock approximation. The periodicity of Mendeleev's table is regained for the first time through the evaluation of a QSM. Evaluation of the information theory based QSI demonstrates, however, that the patterns of periodicity are lost due to the renormalization of the QSM, yielding chemically less appealing results for the QSI. A comparison of the information content of a given atom on top of a group with the information content of the elements in the subsequent rows reveals another periodicity pattern. Relativistic effects on the electronic density functions of atoms are investigated. Their importance is quantified in a QSI study by comparing for each atom, the density functions evaluated in the Hartree-Fock and Dirac-Fock approximations. The smooth decreasing of the relevant QSI along the periodic table illustrates in a quantitative way the increase of relativistic corrections with the nuclear charge. PMID- 17286459 TI - On the locus of points of conical intersection: seams near seams. AB - The existence of a seam of conical intersection, the reference seam, does not rule out the existence of additional disjoint seams of conical intersection. These disjoint seams intersect the g-h planes of the reference seam, a region usually assumed to be devoid of intersections, potentially leading to unexpected points of degeneracy in close proximity to the original conical intersection. Here the authors show how the locus of these disjoint seams can be predicted employing a Hamiltonian derived from second-order perturbation theory. Dramatic differences between the g-h planes of the reference and disjoint seams are found and are expected to have a profound impact on nuclear dynamics. Numerical studies of both high symmetry (D(3h), C(3)H(3)) and low symmetry (C(2v), C(2)H(2)N) species are presented. PMID- 17286458 TI - London dispersion forces by range-separated hybrid density functional with second order perturbational corrections: the case of rare gas complexes. AB - A satisfactory account of the van der Waals (vdW) (London dispersion) forces is, in general not possible by the Kohn-Sham method using standard local, semilocal generalized gradient approximation (GGA), or meta-GGA density functionals. The recently proposed range-separated hybrid (RSH) approach, supplemented by second order perturbational corrections (MP2) to include long-range dynamic correlation effects, offers a physically consistent, seamless description of dispersion forces. It is based on a rigorous generalization of the Kohn-Sham method, where long-range exchange and correlation effects are treated by wave function methods, while short-range electron exchange and correlation are handled by local or semilocal functionals. The method is tested on a series of rare gas dimers in comparison with standard wave function theory and density functional theory approaches. In contrast to the most successful exchange correlation functionals, which describe at best the vdW minimum, the RSH+MP2 approach is valid also in the asymptotic region and the potential curve displays the correct 1/R(6) behavior at large internuclear separations. In contrast to usual MP2 calculations, the basis set superposition error is considerably reduced, making RSH+MP2 an ideal tool for exploring the potential energy surface of weakly bound molecular complexes. PMID- 17286460 TI - Direct dynamics simulations using Hessian-based predictor-corrector integration algorithms. AB - In previous research [J. Chem. Phys. 111, 3800 (1999)] a Hessian-based integration algorithm was derived for performing direct dynamics simulations. In the work presented here, improvements to this algorithm are described. The algorithm has a predictor step based on a local second-order Taylor expansion of the potential in Cartesian coordinates, within a trust radius, and a fifth-order correction to this predicted trajectory. The current algorithm determines the predicted trajectory in Cartesian coordinates, instead of the instantaneous normal mode coordinates used previously, to ensure angular momentum conservation. For the previous algorithm the corrected step was evaluated in rotated Cartesian coordinates. Since the local potential expanded in Cartesian coordinates is not invariant to rotation, the constants of motion are not necessarily conserved during the corrector step. An approximate correction to this shortcoming was made by projecting translation and rotation out of the rotated coordinates. For the current algorithm unrotated Cartesian coordinates are used for the corrected step to assure the constants of motion are conserved. An algorithm is proposed for updating the trust radius to enhance the accuracy and efficiency of the numerical integration. This modified Hessian-based integration algorithm, with its new components, has been implemented into the VENUS/NWChem software package and compared with the velocity-Verlet algorithm for the H(2)CO-->H(2)+CO, O(3)+C(3)H(6), and F(-)+CH(3)OOH chemical reactions. PMID- 17286461 TI - Atomic quantum similarity indices in position and momentum spaces. AB - Quantum similarity for atoms is investigated using electron densities in position and momentum spaces. Contrary to the results in position space, the analysis in the momentum space shows how the momentum density carries fundamental information about periodicity and structure of the system and reveals the pattern of Mendeleev's table. A global analysis in the joint r-p space keeps this result. PMID- 17286462 TI - Efficient global biopolymer sampling with end-transfer configurational bias Monte Carlo. AB - We develop an "end-transfer configurational bias Monte Carlo" method for efficient thermodynamic sampling of complex biopolymers and assess its performance on a mesoscale model of chromatin (oligonucleosome) at different salt conditions compared to other Monte Carlo moves. Our method extends traditional configurational bias by deleting a repeating motif (monomer) from one end of the biopolymer and regrowing it at the opposite end using the standard Rosenbluth scheme. The method's sampling efficiency compared to local moves, pivot rotations, and standard configurational bias is assessed by parameters relating to translational, rotational, and internal degrees of freedom of the oligonucleosome. Our results show that the end-transfer method is superior in sampling every degree of freedom of the oligonucleosomes over other methods at high salt concentrations (weak electrostatics) but worse than the pivot rotations in terms of sampling internal and rotational sampling at low-to-moderate salt concentrations (strong electrostatics). Under all conditions investigated, however, the end-transfer method is several orders of magnitude more efficient than the standard configurational bias approach. This is because the characteristic sampling time of the innermost oligonucleosome motif scales quadratically with the length of the oligonucleosomes for the end-transfer method while it scales exponentially for the traditional configurational-bias method. Thus, the method we propose can significantly improve performance for global biomolecular applications, especially in condensed systems with weak nonbonded interactions and may be combined with local enhancements to improve local sampling. PMID- 17286463 TI - Density functional theory optimized basis sets for gradient corrected functionals: 3d transition metal systems. AB - Density functional theory optimized basis sets for gradient corrected functionals for 3d transition metal atoms are presented. Double zeta valence polarization and triple zeta valence polarization basis sets are optimized with the PW86 functional. The performance of the newly optimized basis sets is tested in atomic and molecular calculations. Excitation energies of 3d transition metal atoms, as well as electronic configurations, structural parameters, dissociation energies, and harmonic vibrational frequencies of a large number of molecules containing 3d transition metal elements, are presented. The obtained results are compared with available experimental data as well as with other theoretical data from the literature. PMID- 17286464 TI - Electronic absorption spectra of the protonated polyacetylenes HC2nH2+ (n=3,4) in the gas phase. AB - A new approach has been developed for the purpose of measuring the electronic transitions to bound exited states for cations that have been collisionally relaxed to low vibrational and rotational temperatures. This has been used to obtain the first gas phase electronic spectra of the protonated polyacetylenes using a two-color ion-photodissociation approach. Specifically, the origin bands in the B (1)A(1)<-- X(1)A(1) transitions of HC(6)H(2) (+) and HC(8)H(2) (+) (C(2v) geometry) were observed at 26,403.3 and 21,399.8 cm(-1). Data on such cooled systems allow a direct comparison between laboratory and astrophysical measurements. PMID- 17286465 TI - Butterfly C2H2++: new way for the decomposition of the acetylene dication. AB - Using highly correlated ab initio methods, a new transition state is characterized in the lowest singlet potential energy surface of HCCH(++). This transition state possesses a dibridged (or "butterfly") form not observed yet for any acetylic compound. It can be reached either directly or after spin-orbit conversion of triplet HCCH(++) ions. In light of these calculations, a reaction pathway for the proton pair formation (i.e., HCCH(++)-->C(2)+H(+)+H(+)) is proposed. PMID- 17286466 TI - Structure and properties of polycoordinate planar boron compounds. AB - Polycoordinate planar B compounds BX(n) (X=B, Al, C, N and Si; n=3-8) are optimized at B3LYP/6-311++G (3df,p) theoretical level. For X=B, center B atom can coordinate three to eight atoms, while for X=Al, C, Si, and N, it can only coordinate three to five atoms. The natural bond orbital analysis shows that the center B atom does not violate the octet rule, though the numbers of coordinated atom even reach 8. According to molecular orbital analysis and nucleus independent chemical shift value calculation, it seems that these polycoordinate planar B compounds BX(n) (X=B, Al, C, N, and Si; n=3-8) hold twofold (alpha and pi) aromatic, which play an important role in their stability and keeping all atoms in one plane. PMID- 17286467 TI - Photolysis of allene and propyne in the 7-30 eV region probed by the visible fluorescence of their fragments. AB - The photolysis of allene and propyne, two isomers of C(3)H(4), has been investigated in the excitation energy range of 7-30 eV using vacuum ultraviolet synchrotron radiation. The visible fluorescence excitation spectra of the excited neutral photofragments of both isomers were recorded within the same experimental conditions. Below the first ionization potential (IP), this fluorescence was too weak to be dispersed and possibly originated from C(2)H or CH(2) radicals. Above IP, three excited photofragments have been characterized by their dispersed emission spectra: the CH radical (A (2)Delta-X (2)Pi), the C(2) radical (d (3)Pi(g)-a (3)Pi(u), "Swan's bands"), and the H atom (4-2 and 3-2 Balmer lines). A detailed analysis of the integrated emission intensities allowed us to determine several apparition thresholds for these fragments, all of them being interpreted as rapid and barrierless dissociation processes on the excited potential energy surfaces. In the low energy range explored in this work, both isomers exhibit different intensity distributions in their fragment emission as a function of the photolysis energy, indicating that mutual allene<-->propyne isomerization is not fully completed before dissociation occurs. The effect of isomerization on the dissociation into excited fragments is present in the whole excitation energy range albeit less important in the 7-16 eV region; it gradually increases with increasing excitation energy. Above 19 eV, the fragment distribution is very similar for the two isomers. PMID- 17286468 TI - Microcanonical statistical study of ortho-para conversion in the reaction H3+ + H2-->(H5+)*-->H3+ + H2 at very low energies. AB - The ortho-para conversion of H(3) (+) and H(2) in the reaction H(3) (+)+H(2)- >(H(5) (+))(*)-->H(3) (+)+H(2) in interstellar space is possible by scrambling the five protons via (H(5) (+))(*) complex formation. The product distribution of the ortho-para conversion reaction can be given by ratios of cumulative reaction probabilities (CRP) calculated by microcanonical statistical theory with conservation of energy, motional angular momentum, nuclear spin, and parity. A statistical method to calculate the state-to-state reaction probabilities for given initial nuclear spin species, rotational states, and collision energies is developed using a simple semiclassical approximation of tunneling and above barrier reflection. A new calculation method of branching ratios for given total nuclear spins and scrambling mechanisms is also developed. The anisotropic long range electrostatic interaction potential of H(2) in the Coulomb field of H(3) (+) is taken into account using the first-order perturbation theory in forming the complex. The CRPs and the product distribution of the ortho-para conversion reaction at very low energies with reactants in their ground vibronic and lowest rotational states for given initial nuclear spin species are presented as a function of collision energy assuming complete proton scrambling or incomplete proton scrambling. The authors show that the product distribution at very low energies (or very low temperatures) differs substantially from the high energy (or high temperature) limit branching ratios. PMID- 17286469 TI - Electronic excitations of fluoroethylenes. AB - Several lowest-lying singlet electronic states of vinyl fluoride, trans-, cis-, and 1,1-difluoroethylene, trifluoroethylene, and tetrafluoroethylene were investigated by using symmetry-adapted cluster configuration interaction theory. Basis sets up to Dunning's aug-cc-pVTZ augmented with appropriate Rydberg functions were utilized for the calculations. Calculated excitation energies show a good agreement with the available experimental values. Even in the troublesome pi-->pi(*) transitions, the excitation energies obtained in the present study agree well with the experimental values except in one or two fluoroethylenes. Strong mixing between different states was noticed in a few fluoroethylenes; especially the mixing is very strong between pi-pi(*) and pi-3ppi states in trifluoroethylene. No pure pi-sigma(*) excited state was found in almost all the fluoroethylenes. Several assignments and reassignments of features in the experimental spectra were suggested. The present study does not support the existing argument that the interaction between the pi-pi(*) and sigma-sigma(*) states is the reason behind the blueshift of around 1.25 eV in the pi-pi(*) excitation energy of tetrafluoroethylene. Possible reasons, including structural changes, for this shift are discussed in detail. Several low-lying triplet excited states were also studied. PMID- 17286470 TI - Laser-induced fluorescence and pure rotational spectroscopy of the CH2CHS (vinylthio) radical. AB - Laser-induced fluorescence (LIF) excitation spectra of the B-X (2)A(") electronic transition of the CH(2)CHS radical, which is the sulfur analog of the vinoxy (CH(2)CHO) radical, were observed under room temperature and jet-cooled conditions. The LIF excitation spectra show very poor vibronic structures, since the fluorescence quantum yields of the upper vibronic levels are too small to detect fluorescence, except for the vibrationless level in the B state. A dispersed fluorescence spectrum of jet-cooled CH(2)CHS from the vibrationless level of the B state was also observed, and vibrational frequencies in the X state were determined. Precise rotational and spin-rotation constants in the ground vibronic level of the radical were determined from pure rotational spectroscopy using a Fourier-transform microwave (FTMW) spectrometer and a FTMW millimeter wave double-resonance technique [Y. Sumiyoshi et al., J. Chem. Phys. 123, 054324 (2005)]. The rotationally resolved LIF excitation spectrum for the vibronic origin band of the jet-cooled CH(2)CHS radical was analyzed using the ground state molecular constants determined from pure rotational spectroscopy. Determined molecular constants for the upper and lower electronic states agree well with results of ab initio calculations. PMID- 17286471 TI - Probing the O2 (a 1Delta g) photofragment following ozone dissociation within the long wavelength tail of the Hartley band. AB - The technique of resonance enhanced multiphoton ionization (REMPI) has been used in conjunction with time-of-flight mass spectrometry (TOFMS), to investigate the dynamics of ozone photolysis in the long wavelength region of the Hartley band (301-311 nm). Specifically, both the translational anisotropy and the rotational angular momentum orientation of the O(2) (a (1)Delta(g); nu=0, J=16-20) fragments have been measured as a function of photolysis wavelength. Within this region, the thermodynamic thresholds for the formation of these products in combination with O ((1)D(2)) are approached and passed, and consequently these studies have allowed an investigation into the effects on the dynamics of slowing fragment recoil velocities and the increasing importance of vibrationally mediated photolysis. The determined beta parameters for all the J states probed follow a similar trend, decreasing from a value typical for the initial (1)B(2)<--(1)A(1) excitation responsible for the Hartley band [for example, beta=1.40+/-0.12 for the O(2) (a (1)Delta(g); J=18) fragment], to a much lower value beyond the thermodynamic threshold for the fragment's production (for example, beta=0.63+/ 0.19 for the J=18 fragment following photolysis at 311 nm). This trend, similar to that observed when probing the atomic fragment in a previous set of experiments, [Horrocks et al., J. Chem. Phys. 125, 133313 (2006); Denzer et al., Phys. Chem. Chem. Phys. 16, 1954 (2006)] is consistent with the photodissociation of vibrationally excited ozone molecules beyond the threshold wavelengths and we estimate approximately 1/3 of this to be from excitation in the nu(3) asymmetric stretching mode. These observations are substantiated by the values of the beta(0) (2)(2,1) orientation moment measured, which for photolysis at 301 nm are negative, indicating that a bond opening mechanism provides the key torque for the departing O(2) fragment. The orientation moment becomes positive again for photolysis beyond threshold, however, as the increasing impulsive dissociation again begins to dominate the nature of the rotation of the departing molecular fragment. In addition, a (2+2) REMPI scheme has been utilized to probe the O(2) (a (1)Delta(g)) "low" J fragments, where the majority of the population resides following photolysis within this region. The REMPI-TOFMS technique has been used to confirm the rotational character of a spectral feature through examination of the signal line shapes obtained using different experimental geometries. The dynamical information subsequently obtained, probing the "low" J O(2) (a (1)Delta(g)) fragments on these rotational transitions, has unified previous translational anisotropy results obtained by detecting the O ((1)D(2)) atomic fragment with data for the O(2) (a (1)Delta(g); J=16-20) fragments. PMID- 17286472 TI - Simple systematization of vibrational excitation cross-section calculations for resonant electron-molecule scattering in the boomerang and impulse models. AB - Vibrational excitation (nu(f)<--nu(i)) cross-sections sigma(nu(f)<--nu(i) )(E) in resonant e-N(2) and e-H(2) scattering are calculated from transition matrix elements T(nu(f),nu(i) )(E) obtained using Fourier transform of the cross correlation function , where psi(nu(i))(R,t) approximately =e(-iH(A(2))-(R)t/h phi(nu(i))(R) with time evolution under the influence of the resonance anionic Hamiltonian H(A(2) (-))(A(2) (-)=N(2)(-)/H(2) (-)) implemented using Lanczos and fast Fourier transforms. The target (A(2)) vibrational eigenfunctions phi(nu(i))(R) and phi(nu(f))(R) are calculated using Fourier grid Hamiltonian method applied to potential energy (PE) curves of the neutral target. Application of this simple systematization to calculate vibrational structure in e-N(2) and e-H(2) scattering cross-sections provides mechanistic insights into features underlying presence/absence of structure in e N(2) and e-H(2) scattering cross-sections. The results obtained with approximate PE curves are in reasonable agreement with experimental/calculated cross-section profiles, and cross correlation functions provide a simple demarcation between the boomerang and impulse models. PMID- 17286473 TI - N-level Li2 multiphoton rotational wave packets: alignment effects in resonant multiphoton coherent excitation. AB - Using one color ultrafast pump-probe spectroscopy, the authors create N-level multiphoton rotational wave packets via resonant optical pumping between the A((1)Sigma(u) (+)) and E((1)Sigma(g) (+)) electronically bound states of Li(2) from a single optically state-selected rovibrational state |nu(A)=11, j(A)=28>. The authors find that excitation with a single amplitude shaped femtosecond pulse allows the direct observation of up to a six photon absorption, which generates a coherent superposition of 13 rotational states. The multilevel rotational wave packet is theoretically treated with the multipole moment formalism in order to characterize the experimentally observed time-dependent alignment. In particular, the authors find that the magnetic state distributions measured among coherently excited rotational states generated by the resonant multiphoton pumping reduces the measured coherence amplitudes by as much as 40%. PMID- 17286475 TI - Unimolecular thermal fragmentation of ortho-benzyne. AB - The ortho-benzyne diradical, o-C(6)H(4) has been produced with a supersonic nozzle and its subsequent thermal decomposition has been studied. As the temperature of the nozzle is increased, the benzyne molecule fragments: o C(6)H(4)+Delta--> products. The thermal dissociation products were identified by three experimental methods: (i) time-of-flight photoionization mass spectrometry, (ii) matrix-isolation Fourier transform infrared absorption spectroscopy, and (iii) chemical ionization mass spectrometry. At the threshold dissociation temperature, o-benzyne cleanly decomposes into acetylene and diacetylene via an apparent retro-Diels-Alder process: o-C(6)H(4)+Delta-->HC triple bond CH+HC triple bond C-C triple bond CH. The experimental Delta(rxn)H(298)(o-C(6)H(4)-->HC triple bond CH+HC triple bond C-C triple bond CH) is found to be 57+/-3 kcal mol( 1). Further experiments with the substituted benzyne, 3,6-(CH(3))(2)-o-C(6)H(2), are consistent with a retro-Diels-Alder fragmentation. But at higher nozzle temperatures, the cracking pattern becomes more complicated. To interpret these experiments, the retro-Diels-Alder fragmentation of o-benzyne has been investigated by rigorous ab initio electronic structure computations. These calculations used basis sets as large as [C(7s6p5d4f3g2h1i)H(6s5p4d3f2g1h)] (cc pV6Z) and electron correlation treatments as extensive as full coupled cluster through triple excitations (CCSDT), in cases with a perturbative term for connected quadruples [CCSDT(Q)]. Focal point extrapolations of the computational data yield a 0 K barrier for the concerted, C(2v)-symmetric decomposition of o benzyne, E(b)(o-C(6)H(4)-->HC triple bond CH+HC triple bond C-C triple bond CH)=88.0+/-0.5 kcal mol(-1). A barrier of this magnitude is consistent with the experimental results. A careful assessment of the thermochemistry for the high temperature fragmentation of benzene is presented: C(6)H(6)-->H+[C(6)H(5)]-->H+[o C(6)H(4)]-->HC triple bond CH+HC triple bond C-C triple bond CH. Benzyne may be an important intermediate in the thermal decomposition of many alkylbenzenes (arenes). High engine temperatures above 1500 K may crack these alkylbenzenes to a mixture of alkyl radicals and phenyl radicals. The phenyl radicals will then dissociate first to benzyne and then to acetylene and diacetylene. PMID- 17286474 TI - Conformational dependence of intramolecular vibrational redistribution in methanol. AB - Previous state-selected spectra of methanol in the 5nu(1) OH stretch overtone region [O. V. Boyarkin, T. R. Rizzo, and D. S. Perry, J. Chem. Phys. 110, 11346 (1999)] revealed a structure indicating an intramolecular vibrational redistribution on three time scales. Whereas in that work, methanol in the 5nu(1) bright state was prepared close to the staggered conformation, methanol in the "partially eclipsed" conformation is prepared here by double resonance excitation through a torsionally excited intermediate state. The excited molecules are detected by infrared laser assisted photofragment spectroscopy. In partially eclipsed methanol, the strong coupling of the nu(1) OH stretch to the nu(2) CH stretch becomes weaker, but the coupling responsible for the widths of the narrowest features becomes stronger. PMID- 17286476 TI - The vibrational structure of the X 1A1 - A 1B1 and A 1B1 - B 1A1 band systems of GeH2/GeD2 based on global potential energy surfaces. AB - Transition probabilities were evaluated for the X (1)A(1)-A (1)B(1) and A (1)B(1) B (1)A(1) systems of GeH(2) and GeD(2) to analyze the X-->A-->B photoexcitation. Franck-Condon factors (FCFs) and Einstein's B coefficients were computed by quantum vibrational calculations using the three-dimensional potential energy surfaces (PESs) of the X (1)A(1), A (1)B(1), and B (1)A(1) electronic states and the transition dipole moments for the X-A and A-B systems. The global PESs were determined by the multireference configuration interaction calculations with the Davidson correction and the interpolant moving least squares method combined with the Shepard [Proceedings of the 1968 23rd ACM National Conference (ACM, New York, 1968)] interpolation. The barriers to linearity correcting the spin-orbit interaction are evaluated to be 22,000 cm(-1) for the X state, 6300 cm(-1) for the A state, and 560 cm(-1) for the B state. The obtained FCFs for the X-A and A B systems indicate that the bending mode is strongly enhanced in the excitation since the equilibrium bond angle greatly varies within the three states. The photoexcitation and fluorescence spectra calculated for the X-A system agree well with the observed spectra. The theoretical lifetimes for lower vibrational levels of the A and B states were calculated from the fluorescence decay rates for the A X, B-A, and B-X emissions, and the lifetimes for the A state are in good agreement with the observed values except those affected by predissociation. PMID- 17286477 TI - Energy dependence of the roaming atom pathway in formaldehyde decomposition. AB - Recently, a new mechanism of formaldehyde decomposition leading to molecular products CO and H(2) has been discovered, termed the "roaming atom" mechanism. Formaldehyde decomposition from the ground state via the roaming atom mechanism leads to rotationally cold CO and vibrationally hot H(2), whereas formaldehyde decomposition through the conventional molecular channel leads to rotationally hot CO and vibrationally cold H(2). This discovery has shown that it is possible to have multiple pathways for a reaction leading to the same products with dramatically different product state distributions. Detailed investigations of the dynamics of these two pathways have been reported recently. This paper focuses on an investigation of the energy dependence of the roaming atom mechanism up to 1500 cm(-1) above the threshold of the radical channel, H(2)CO- >H+HCO. The influence of excitation energy on the roaming atom and molecular elimination pathways is reported, and the branching fraction between the roaming atom channel and molecular channel is obtained using high-resolution dc slice imaging and photofragment excitation spectroscopy. From the branching fractions and the reaction rates of the radical channel, the overall competition between all three dissociation channels is estimated. These results are compared with recent quasiclassical trajectory calculations on a global H(2)CO potential energy surface. PMID- 17286478 TI - Reaction of Cl with CD4 excited to the second C-D stretching overtone. AB - The effects of vibrational excitation on the Cl+CD(4) reaction are investigated by preparing three nearly isoenergetic vibrational states: mid R:3000 at 6279.66 cm(-1), |2100> at 6534.20 cm(-1), and |1110> at 6764.24 cm(-1), where |D(1)D(2)D(3)D(4)> identifies the number of vibrational quanta in each C-D oscillator. Vibrational excitation of the perdeuteromethane is via direct infrared pumping. The reaction is initiated by photolysis of molecular chlorine at 355 nm. The nascent methyl radical product distribution is measured by 2+1 resonance-enhanced multiphoton ionization at 330 nm. The resulting CD(3) state distributions reveal a preference to remove all energy available in the most excited C-D oscillator. Although the energetics are nearly identical, the authors observe strong mode specificity in which the CD(3) state distributions markedly differ between the three Cl-atom reactions. Reaction with CD(4) prepared in the |3000> mode leads to CD(3) products populated primarily in the ground state, reaction with CD(4) prepared in the |2100> mode leads primarily to CD(3) with one quantum of stretch excitation, and reaction with CD(4) prepared in the |1110> mode leads primarily to CD(3) with one quantum of C-D stretch excitation in two oscillators. There are some minor deviations from this behavior, most notably that the Cl atom is able to abstract more energy than is available in a single C D oscillator, as in the case of |2100>, wherein a small population of ground state CD(3) is observed. These exceptions likely result from the mixings between different second overtone stretch combination bands. They also measure isotropic and anisotropic time-of-flight profiles of CD(3) (nu(1)=1,2) products from the Cl+CD(4) |2100> reaction, providing speed distributions, spatial anisotropies, and differential cross sections that indicate that energy introduced as vibrational energy into the system essentially remains as such throughout the course of the reaction. PMID- 17286479 TI - Ionization and dissociation of CH3I in intense laser field. AB - The ionization-dissociation of methyl iodide in intense laser field has been studied using a reflection time-of-flight mass spectrometry (RTOF-MS), at a laser intensity of < or =6.6x10(14) W/cm(2), lambda=798 nm, and a pulse width of 180 fs. With the high resolution of RTOF-MS, the fragment ions with the same M/z but from different dissociation channels are resolved in the mass spectra, and the kinetic energy releases (KERs) of the fragment ions such as I(q+) (q=1-6), CH(m) (+) (m=0-3), C(2+), and C(3+) are measured. It is found that the KERs of the fragment ions are independent of the laser intensity. The fragments CH(3) (+) and I(+) with very low KERs (<1 eV for CH(3) (+) and <0.07 eV for I(+)) are assigned to be produced by the multiphoton dissociation of CH(3)I(+). For the fragments CH(3) (+) and I(+) from CH(3)I(2+), they are produced by the Coulomb explosion of CH(3)I(2+) with the interaction from the covalent force of the remaining valence electrons. The split of the KER of the fragments produced from CH(3)I(2+) dissociation is observed experimentally and explained with the energy split of I(+)((3)P(2)) and I(+)((3)P(0,1)). The dissociation CH(3)I(3+)-->CH(3) (+)+I(2+) is caused by Coulomb explosion. The valid charge distance R(c) between I(2+) and CH(3) (+), at which enhanced ionization of methyl iodide occurs, is obtained to be 3.7 A by the measurements of the KERs of the fragments CH(3) (+) and I(2+). For the CH(3)I(n+) (n> or =3), the KERs of the fragment ions CH(3) (p+) and I(q+) are attributed to the Coulomb repulsion between CH(3) (p+) and I(q+) from R(c) approximately 3.7 A. The dissociation of the fragment CH(3) (+) is also discussed. By the enhanced ionization mechanism and using the measured KER of I(q+), all the possible Coulomb explosion channels are identified. By comparing the abundance of fragment ions in mass spectrum, it is found that the asymmetric dissociation channels with more charges on iodine, q>p, are the dominant channels. PMID- 17286480 TI - Effect of the geometric phase on the dynamics of the hydrogen-exchange reaction. AB - A recent puzzle in nonadiabatic quantum dynamics is that geometric phase (GP) effects are present in the state-to-state opacity functions of the hydrogen exchange reaction, but cancel out in the state-to-state integral cross sections (ICSs). Here the authors explain this result by using topology to separate the scattering amplitudes into contributions from Feynman paths that loop in opposite senses around the conical intersection. The clockwise-looping paths pass over one transition state (1-TS) and scatter into positive deflection angles; the counterclockwise-looping paths pass over two transition states (2-TS) and scatter into negative deflection angles. The interference between the 1-TS and 2-TS paths thus integrates to a very small value, which cancels the GP effects in the ICS. Quasiclassical trajectory (QCT) calculations reproduce the scattering of the 1-TS and 2-TS paths into positive and negative deflection angles and show that the 2 TS paths describe a direct insertion mechanism. The inserting atom follows a highly constrained "S-bend" path, which allows it to avoid both the other atoms and the conical intersection and forces the product diatom to scatter into high rotational states. By contrast, the quantum 2-TS paths scatter into a mainly statistical distribution of rotational states, so that the quantum 2-TS total ICS is roughly twice the QCT ICS at 2.3 eV total energy. This suggests that the S bend constraint is relaxed by tunneling in the quantum system. These findings on H+H(2) suggest that similar cancellations or reductions in GP effects are likely in many other reactions. PMID- 17286482 TI - Recovering the Crooks equation for dynamical systems in the isothermal-isobaric ensemble: a strategy based on the equations of motion. AB - The Crooks equation [Eq. (10) in J. Stat. Phys. 90, 1481 (1998)] relates the work done on a system during a nonequilibrium transformation to the free energy difference between the final and the initial state of the transformation. Recently, the authors have derived the Crooks equation for systems in the canonical ensemble thermostatted by the Nose-Hoover or Nose-Hoover chain method [P. Procacci et al., J. Chem. Phys. 125, 164101 (2006)]. That proof is essentially based on the fluctuation theorem by Evans and Searles [Adv. Phys. 51, 1529 (2002)] and on the equations of motion. Following an analogous approach, the authors derive here the Crooks equation in the context of molecular dynamics simulations of systems in the isothermal-isobaric (NPT) ensemble, whose dynamics is regulated by the Martyna-Tobias-Klein algorithm [J. Chem. Phys. 101, 4177 (1994)]. Their present derivation of the Crooks equation correlates to the demonstration of the Jarzynski identity for NPT systems recently proposed by Cuendet [J. Chem. Phys. 125, 144109 (2006)]. PMID- 17286481 TI - On the influence of solute polarizability on the hydrophobic interaction. AB - The authors have performed molecular dynamics simulations of polarizable solutes in water to investigate how solute polarizability affects solute-solute hydrophophic interactions. A degree of polarization similar to the one expected in biomolecules, corresponding to a dielectric response of epsilon=2-20, results in dramatic changes in the hydrophobic forces. They find that this degree of polarizability is enough to inhibit drying between hydrophobic solutes and to stabilize a reduced water density phase whose density is smaller than the bulk water density. The hydrophobic forces associated with such reduced density states are still very significant with values of the order of several tens of piconewtons. Their results suggest that polarizability plays an important role in determining the hydrophobic force acting between weakly polar surfaces. PMID- 17286483 TI - Local density augmentation and dynamic properties of hydrogen-and non-hydrogen bonded supercritical fluids: a molecular dynamics study. AB - The local density inhomogeneities in neat supercritical fluids were investigated via canonical molecular dynamics simulations. The selected systems under investigation were the polar and hydrogen-bonded fluid methanol as well as the quadrupolar non-hydrogen-bonded carbon dioxide one. Effective local densities, local density augmentation, and enhancement factors were calculated at state points along an isotherm close to the critical temperature of each system (T(r)=1.03). The results obtained reveal strong influence of the polarity and hydrogen bonding upon the intensity of the local density augmentation. It is found that this effect is sufficiently larger in the case of the polar and associated methanol in comparison to those predicted for carbon dioxide. For both fluids the local density augmentation values are maximized in the bulk density region near 0.7rho(c), a result that is in agreement with experiment. In addition, the local density dynamics of each fluid were investigated in terms of the appropriate time correlation functions. The behavior of these functions reveals that the bulk density dependence of the local density reorganization times is very sensitive to the specific intermolecular interactions and to the size of the local region. Also, the estimated local density reorganization time as a function of bulk density of each fluid was further analyzed and successfully related to two different time-scale relaxation mechanisms. Finally, the results obtained indicate a possible relationship between the single-molecule reorientational dynamics and the local density reorganization ones. PMID- 17286484 TI - Statistical-mechanical theory of ultrasonic absorption in molecular liquids. AB - We present results of the theoretical description of ultrasonic phenomena in molecular liquids. In particular, we are interested in the development of a microscopical, i.e., statistical-mechanical, framework capable of explaining the long living puzzle of excess ultrasonic absorption in liquids. Typically, an ultrasonic wave in a liquid can be generated by applying a periodically alternating external pressure with an angular frequency that corresponds to the ultrasound. If the perturbation introduced by such a process is weak, its statistical-mechanical treatment can be done with the use of a linear response theory. We treat the liquid as a system of interacting sites, so that all the response/aftereffect functions as well as the energy dissipation and generalized (wave-vector and frequency-dependent) ultrasonic absorption coefficient are obtained in terms of familiar site-site static and time correlation functions such as static structure factors or intermediate scattering functions. To express the site-site intermediate scattering functions, we refer to the site-site memory equations in the mode-coupling approximation for first-order memory kernels, while equilibrium properties such as site-site static structure factors, and direct and total correlation functions are deduced from the integral equation theory of molecular liquids known as RISM, or one of its generalizations. All of the formalism is phrased in a general manner, hence the results obtained are expected to work for arbitrary types of molecular liquids including simple, ionic, polar, and nonpolar liquids. PMID- 17286485 TI - Concentration fluctuations and collective properties in mixed liquid systems: Rayleigh-Brillouin spectra of tert-butyl alcohol/2,2'-dimethylbutane liquid mixture. AB - Rayleigh-Brillouin spectra have been measured in a range of temperatures and compositions of t-butyl alcohol/2,2(')-dimethylbutane liquid mixture. The mixture mole fraction has been varied from pure alkane (x(TBA)=0) to pure alcohol (x(TBA)=1) at temperatures between 283 and 323 K. In the same composition and temperature ranges the authors also executed measurements of mass density, shear viscosity, and refractive index. From light scattering spectra the authors have extracted the hypersound velocities and adiabatic compressibilities and evaluated their excess values. Moreover, the authors attempted to evaluate the isothermal (40 degrees C) Landau-Placzek ratios at various mole fractions, but these values proved to be subject to significant errors due to great uncertainty in the central component intensity measurements. Thus, in discussing the results, this latter quantity was considered only from a qualitative point of view. These results highlight a nonideal behavior of the studied liquid mixture with a probable azeotropic composition around x(TBA)=0.7 due to formation of small clusters of hydrogen-bonded alcohol tetramers that are completely surrounded by solvent molecules and analogous or smaller clusters. These clusters, shaped as inverse micelles, offer their hydrophobic moiety towards the molecules that constitute the solvation shell, resulting in a low polarity solution structure that minimizes the solute-solvent interactions. Differences in thermal and compositional behavior of excess molar volumes and adiabatic compressibilities have been interpreted by attributing different weights to the solute-solvent interaction forces and to the hydrogen bond connectivity effects. PMID- 17286486 TI - Molecular dynamics simulation of planar elongational flow at constant pressure and constant temperature. AB - Molecular dynamics simulations of liquid systems under planar elongational flow have mainly been performed in the NVT ensemble. However, in most material processing techniques and common experimental settings, at least one surface of the fluid is kept in contact with the atmosphere, thus maintaining the sample in the NpT ensemble. For this reason, an implementation of the Nose-Hoover integral feedback mechanism for constant pressure is presented, implemented via the SLLOD algorithm for elongational flow. The authors test their procedure for an atomic liquid and compare the viscosity obtained with that in the NVT ensemble. The scheme is easy to implement, self-starting and reliable, and can be a useful tool for the simulation of more complex liquid systems, such as polymer melts and solutions. PMID- 17286488 TI - Manipulating multidimensional electronic spectra of excitons by polarization pulse shaping. AB - A simulation study demonstrates how coherent control, combined with adaptive polarization pulse shaping and a genetic algorithm, may be used to simplify femtosecond coherent nonlinear optical signals of excitons. Cross peaks are amplified and resolved, and diagonal peaks are suppressed in the heterodyne detected two-pulse echo signal from the Soret band of a porphyrin dimer coupled to a Brownian oscillator bath. Various optimization strategies involving the spectral, temporal, and polarization profiles of the second pulse are compared. PMID- 17286487 TI - Quantum confinement effect on Gd2O3 clusters. AB - The evolution of the gap of a nanoscaled insulator material, namely, Gd(2)O(3), has been observed by means of vacuum ultraviolet excitation spectra of a dopant (Eu(3+)). The nanoparticles have been synthesized by the low energy cluster beam deposition technique and grown afterward by different annealing steps. A gap shift towards the blue is observed, similar to what is observed in semiconductor nanoparticles. Despite the strong ionic character of the material, the evolution exhibits a behavior similar to covalent materials. The evolution of the gap for Gd(2)O(3) follows the same empiric rule that has been derived for semiconductors (ZnO, CuBr, Si, and CdS). It shows that, in spite of the strong ionic character of the material (0.9 on the scale of Phillips), the amount of covalency is important enough for creating a significant delocalization of the electron with regard to its hole. PMID- 17286489 TI - Effective potentials for 1:1 electrolyte solutions incorporating dielectric saturation and repulsive hydration. AB - Implicit water potentials are developed for the study of thermodynamic and structural properties of solutions of NaCl, LiCl, and KCl. The interaction potential between cations and anions is parametrized from the ionic crystal potential. Two short-range corrections were added to the system to account for the water solvent. The first is due to dielectric saturation which reduces the dielectric permittivity in the vicinity of an ion. The second is a repulsive Gaussian potential which represents the first hydration shell around the ions. Grand canonical Monte Carlo simulations were performed to calculate the mean ionic activity coefficients. Molecular dynamics simulations were performed to calculate the radial distribution functions of 1.0 molal solutions at 298 K which were used to compare the structure of the explicit and implicit water simulations. The implementation of dielectric saturation and a repulsive hydration potential results in an excellent description of the mean activity coefficient and is able to capture structural features of contact ion pairs and solvent separated ions. PMID- 17286490 TI - Phase separation in H2O:N2 mixture: molecular dynamics simulations using atomistic force fields. AB - A class II atomistic force field with Lennard-Jones 6-9 nonbond interactions is used to investigate equations of state (EOS) for important high explosive detonation products N(2) and H(2)O in the temperature range of 700-2500 K and pressure range of 0.1-10 GPa. A standard sixth order parameter-mixing scheme is then employed to study a 2:1 (molar) H(2)O:N(2) mixture, to investigate, in particular, the possibility of phase separation under detonation conditions. The simulations demonstrate several important results, including (i) the accuracy of computed EOS for both N(2) and H(2)O over the entire range of temperature and pressure considered, (ii) accurate mixing-demixing phase boundary as compared to experimental data, and (iii) the departure of mixing free energy from that predicted by ideal mixing law. The results provide comparison and guidance to state-of-the-art chemical kinetic models. PMID- 17286491 TI - Propagation, beam geometry, and detection distortions of peak shapes in two dimensional Fourier transform spectra. AB - Using a solution of Maxwell's equations in the three-dimensional frequency domain, femtosecond two-dimensional Fourier transform (2DFT) spectra that include distortions due to phase matching, absorption, dispersion, and noncollinear excitation and detection of the signal are calculated for Bloch, Kubo, and Brownian oscillator relaxation models. For sample solutions longer than a wavelength, the resonant propagation distortions are larger than resonant local field distortions by a factor of approximately L/lambda, where L is the sample thickness and lambda is the optical wavelength. For the square boxcars geometry, the phase-matching distortion is usually least important, and depends on the dimensionless parameter, L sin(2)(beta)Deltaomega/(nc), where beta is the half angle between beams, n is the refractive index, c is the speed of light, and Deltaomega is the width of the spectrum. Directional filtering distortions depend on the dimensionless parameter, [(Deltaomega)w(0) sin(beta)/c](2), where w(0) is the beam waist at the focus. Qualitatively, the directional filter discriminates against off diagonal amplitude. Resonant absorption and dispersion can distort 2D spectra by 10% (20%) at a peak optical density of 0.1 (0.2). Complicated distortions of the 2DFT peak shape due to absorption and dispersion can be corrected to within 10% (15%) by simple operations that require knowledge only of the linear optical properties of the sample and the distorted two-dimensional spectrum measured at a peak optical density of up to 0.5 (1). PMID- 17286492 TI - High-frequency dynamic nuclear polarization using mixtures of TEMPO and trityl radicals. AB - In a previous communication [Hu et al., J. Am. Chem. Soc. 126, 10844 (2004)], an approach was demonstrated that improves the efficiency of the cross-effect polarization mechanism employed in high field dynamic nuclear polarization (DNP) experiments. Specifically, it was shown that tethering two TEMPO (2,2,6,6 tetramethylpiperidin-1-oxyl) radicals increases the electron-electron dipole coupling from approximately 1 MHz in solutions of monomeric TEMPO to approximately 25 MHz in a tethered biradical. The larger coupling resulted in an increase in the DNP enhancements by a factor of approximately 3-4, from 45-50 to approximately 165. Here, a second approach to improving the efficiency of the polarization process is described that involves approximately satisfying the matching condition |omega(2e)-omega(1e)|=omega(n), where omega(2e) and omega(1e) are two frequencies in the electron paramagnetic resonance (EPR) spectrum and omega(n) is the Larmor frequency of the nuclear spins being polarized. Specifically, in a mixture of TEMPO and trityl [tris (8-carboxy-2,2,6,6 tetramethyl(-d3)-benzo[1,2d:4,5-d']bis(1,3)dithiol-4-yl) methyl] radicals, the intensity maxima in the EPR spectra of these two species are approximately separated by the (1)H NMR frequency. In this case the frequency difference between the g(yy) value of TEMPO and the narrow pseudo-isotropic g-value of trityl is approximately 224 MHz and the (1)H Larmor frequency is 211 MHz. The optimal magnetic field for DNP using the mixtures was found to coincide with the trityl EPR resonance. At 90 K and 5 T, a mixture of 20 mM TEMPO and 20 mM trityl enhanced the (1)H polarization by a factor of approximately 160, an improvement over the enhancement of approximately 50 with 40 mM TEMPO. The reasons for the improvement are discussed and evidence is presented suggesting that DNP enhancement can be improved further by tethering TEMPO and trityl or two similar radicals. PMID- 17286494 TI - Dynamics of supercooled water in various mesopore sizes. AB - Double-quantum-filtered NMR and T(1) inversion-recovery spectroscopy were employed to exploit the temperature-dependent dynamics of D(2)O confined in MCM 41. Samples with three pore sizes of 1.58, 2.03, and 2.34 nm and two D(2)O contents were investigated. The reorientation correlation times of confined D(2)O in variously sized pores exhibit different temperature dependencies. The results reveal that the D(2)O molecules at fast motion site remain mobile below approximately 225 K and a liquid-liquid phase transition occurs around this temperature for all samples studied. This temperature is thought to be unreachable for supercooled D(2)O. Particularly, in 20 wt % D(2)O loaded samples with pore diameters of 1.58 and 2.03 nm, the reorientational correlation times of D(2)O at fast motion site exhibit Arrhenius behavior between 225 and 290 K, while other samples show power law dependency. Thus, a liquid phase of the fragile type in bigger pores changes to the strong type in samples with smaller pores. PMID- 17286493 TI - Influence of bond flexibility on the vapor-liquid phase equilibria of water. AB - The authors performed Gibbs ensemble simulations on the vapor-liquid equilibrium of water to investigate the influence of incorporating intramolecular degrees of freedom in the simple point charge (SPC) water model. Results for vapor pressures, saturation densities, heats of vaporization, and the critical point for two different flexible models are compared with data for the corresponding rigid SPC and SPC/E models. They found that the introduction of internal vibrations, and also their parametrization, has an observable effect on the prediction of the vapor-liquid coexistence curve. The flexible SPC/Fw model, although optimized to describe bulk diffusion and dielectric constants at ambient conditions, gives the best prediction of saturation densities and the critical point of the examined models. PMID- 17286495 TI - How much carbon dioxide can be stored in the structure H clathrate hydrates?: a molecular dynamics study. AB - The stability of structure H (sH) carbon dioxide clathrate hydrates at three temperature-pressure conditions are determined by molecular dynamics simulations on a 3x3x3 sH unit cell replica. Simulations are performed at 100 K at ambient pressure, 273 K at 100 bars and also 300 K and 5.0 kbars. The small and medium cages of the sH unit cell are occupied by a single carbon dioxide guest and large cage guest occupancies of 1-5 are considered. Radial distribution functions are given for guests in the large cages and unit cell volumes and configurational energies are studied as a function of large cage CO(2) occupancy. Free energy calculations are carried out to determine the stability of clathrates for large cage occupancies at three temperature/pressure conditions stated above. At the low temperature, large cage occupancy of 5 is the most stable while at the higher temperature, the occupancy of 3 is the most favored. Calculations are also performed to show that the CO(2) sH clathrate is more stable than the methane clathrate analog. Implications on CO(2) sequestration by clathrate formation are discussed. PMID- 17286496 TI - CO oxidation reaction on Pt(111) studied by the dynamic Monte Carlo method including lateral interactions of adsorbates. AB - The dynamics of adsorbate structures during CO oxidation on Pt(111) surfaces and its effects on the reaction were studied by the dynamic Monte Carlo method including lateral interactions of adsorbates. The lateral interaction energies between adsorbed species were calculated by the density functional theory method. Dynamic Monte Carlo simulations were performed for the oxidation reaction over a mesoscopic scale, where the experimentally determined activation energies of elementary paths were altered by the calculated lateral interaction energies. The simulated results reproduced the characteristics of the microscopic and mesoscopic scale adsorbate structures formed during the reaction, and revealed that the complicated reaction kinetics is comprehensively explained by a single reaction path affected by the surrounding adsorbates. We also propose from the simulations that weakly adsorbed CO molecules at domain boundaries promote the island-periphery specific reaction. PMID- 17286497 TI - Stability of silicon-doped C60 dimers. AB - A theoretical investigation on the structure, stability, and thermal behaviors of the smallest polymeric units, the dimers, formed from substitutionally Si-doped fullerenes is presented. A density functional based nonorthogonal tight-binding model has been employed for describing the interatomic interactions. The study focuses on those polymeric structures which involve Si-Si or Si-C interfullerene bonds. The binding energy of the dimers increases with their Si content from about 0.25 eV in C(60)-C(60) to about 4.5 eV in C(58)Si(2)-C(58)Si(2). Moreover, the C(59)SiC(59) dimer, linked through the sharing of the Si atom between the two fullerenes, has been also considered. Upon heating, the dimers eventually fragment into their constituent fullerene units. The fragmentation temperature correlates with the strength of the interfullerene bonds. C(58)Si(2)-C(58)Si(2) exhibits a higher thermal stability (fragmentation temperature of approximately 500 K) than the pure carbon C(60)-C(60) dimer (with a fragmentation temperature of approximately 325 K). Given the higher structural and thermal stabilities of the Si-doped fullerene dimers, the authors propose the use of substitutionally Si doped fullerenes as the basic units for constructing new fullerene-based polymers. PMID- 17286498 TI - Reassessment of the molecular mechanisms for H2 thermal desorption pathways from Si(1-x)Gex(001)-(2x1) surfaces. AB - One of the aims of temperature-programmed desorption experiments is to facilitate identification of molecular pathways for desorption. The authors provide a rigorous assessment of the difficulty of doing this for H(2)/Si((1-x))Ge(x)(100) (2x1). An extensive series of density functional calculations using both cluster and slab methods is performed. The resulting desorption barriers are used to compute thermal desorption spectra. A mean-field approximation is used to treat the populations of the various adsites present on the surface. The authors find a number of significant results. First, slab and cluster calculations do not appear to predict consistent differences in desorption barriers between intradimer and interdimer channels. Second, they find that a germanium atom affects the desorption barrier significantly only if it is present at the adsite. A germanium atom adjacent to an adsite or in the second layer influences the desorption barrier negligibly. Both cluster and slab calculations consistently predict a decrease of approximately 0.3-0.4 eV per germanium atom at the adsite. Third, current analysis of thermal desorption spectra in the literature, although yielding good fits to experimental data, is not rigorous. The authors' calculated spectra can be fitted rather well by assuming, as in current analysis of experimental data, three independent second-order channels, even though the underlying molecular pathways used to calculate the spectra are considerably different. Fourth, the authors' results highlight the importance of treating the rearrangement of hydrogen and germanium atoms at the surface during the thermal desorption process. This is generally not taken into account in kinetics modeling of desorption spectra. PMID- 17286499 TI - Colloidal dynamics near a wall studied by evanescent wave light scattering: experimental and theoretical improvements and methodological limitations. AB - The dynamics of colloidal spheres near to a wall is studied with an evanescent wave scattering setup that allows for an independent variation of the components of the scattering wave vector normal and parallel to the wall. The correlation functions obtained with this novel instrumentation are interpreted on the basis of an expression for their short time behavior that includes hydrodynamic interactions between the colloidal spheres and the wall. The combination of the evanescent wave scattering setup and the exact expression for the short time behavior of correlation functions allows for an unambiguous measurement of the particle mobility parallel and normal to the wall by means of light scattering. It is possible to measure the viscous wall drag effect on the dynamics of particles with radii as small as 27 nm, where, however, the method reaches its limits due to the low scattering intensities of such small particles. PMID- 17286500 TI - Atomistic nature of NaCl nucleation at the solid-liquid interface. AB - The early stage of heterogeneous nucleation of NaCl from supersaturated NaCl aqueous solution at the water-NaCl (001) interface has been investigated by molecular dynamics simulations. The critical size of the nuclei for spontaneous growth was found to be as small as two atoms (a Na(+)-Cl(-) ion pair) at high supersaturation. Due to the presence of a relatively stable water network and the effect of the hydration force at the interface, the stable nuclei formed on the NaCl (001) are found to contain more Na(+) ions than Cl(-) ions. The different deposition characteristics of the Na(+) and Cl(-) solutes lead to a positively charged substrate and thus may introduce another driving force for nucleation besides the level of solution supersaturation. The role of water was further confirmed by comparison with NaCl epitaxy growth in the vacuum. PMID- 17286501 TI - Phase separation in potassium-doped ZnPc thin films. AB - In this study synchrotron radiation was used to investigate the electronic properties of a thin film of zinc-phthalocyanine (ZnPc) deposited on Si(001)-2x1 and progressively doped with K atoms. The molecular orientation was probed by angular-dependent x-ray absorption spectroscopy and the molecules were found to lie with the macrocycle plane roughly perpendicular to the surface. The evolution of the electronic properties of the film was then followed by measuring the photoemission spectra upon in situ evaporation of K atoms on the pristine ZnPc film. The results show that doping proceeds through charge donation from the K atoms to the molecular units whose lowest unoccupied molecular orbital (LUMO) becomes progressively filled. Despite the fact that the LUMO spectral weight increases as the stoichiometry x in the K(x)ZnPc compound varies from about 1 to 4 (as determined by core level photoemission), no detectable density of states was observed at the Fermi level, showing that the film remains insulating for all the investigated stoichiometries. On the other hand the C 1s spectra, which appear merely broadened at the earliest stages of doping (x approximately 1), clearly develop two distinct components when x exceeds 2, suggesting that the charge state is not the same for all the molecules. At the same time, the modification of the valence band points towards the coexistence of two distinct phases with x=2 and x=4. PMID- 17286502 TI - Theory of C2Hx species on Pt{110} (1x2): reaction pathways for dehydrogenation. AB - A complete reaction sequence for molecular dissociation at a surface has been characterized using density functional theory. The barriers for sequential ethane dehydrogenation on Pt{110} are found to fall into distinct energy sets: very low barriers, with values in the range of 0.29-0.42 eV, for the initial ethane dissociation to ethene and ethylidene at the surface; medium barriers, in the range of 0.72-1.10 eV, for dehydrogenation of C(2)H(4) fragments to vinylidene and ethyne; and high barriers, requiring more than 1.45 eV, for further dehydrogenation. For dissociation processes where more than one pathway has been found, the lowest energetic route links the most stable reactant adsorbed state at the surface to a product state involving the hydrocarbon moiety adsorbed in its most stable configuration at the surface. Hence there is a clear link between surface stability and kinetics for these species. PMID- 17286503 TI - Hydrodynamic interaction in polymer solutions simulated with dissipative particle dynamics. AB - The authors analyzed extensively the dynamics of polymer chains in solutions simulated with dissipative particle dynamics (DPD), with a special focus on the potential influence of a low Schmidt number of a typical DPD fluid on the simulated polymer dynamics. It has been argued that a low Schmidt number in a DPD fluid can lead to underdevelopment of the hydrodynamic interaction in polymer solutions. The authors' analyses reveal that equilibrium polymer dynamics in dilute solution, under typical DPD simulation conditions, obey the Zimm [J. Chem. Phys. 24, 269 (1956)] model very well. With a further reduction in the Schmidt number, a deviation from the Zimm model to the Rouse model is observed. This implies that the hydrodynamic interaction between monomers is reasonably developed under typical conditions of a DPD simulation. Only when the Schmidt number is further reduced, the hydrodynamic interaction within the chains becomes underdeveloped. The screening of the hydrodynamic interaction and the excluded volume interaction as the polymer volume fraction is increased are well reproduced by the DPD simulations. The use of soft interaction between polymer beads and a low Schmidt number do not produce noticeable problems for the simulated dynamics at high concentrations, except for the entanglement effect which is not captured in the simulations. PMID- 17286504 TI - Long-time tails of translational and rotational Brownian motion in a suspension of hard spheres. AB - The long-time translational and rotational Brownian motion of a sphere in a suspension of hard spheres is studied on the basis of the linearized Navier Stokes equations and the fluctuation-dissipation theorem. It is shown that for the rotational long-time coefficient an effective medium conjecture is incorrect. There are short-range velocity correlations that decay at the same rate as the macroscopic flow pattern used in the effective medium conjecture. An estimate of the short-range correction is made on the basis of the pair term in the cluster expansion of the rotational admittance. PMID- 17286505 TI - Static polarizability and second hyperpolarizability of closed- and open-shell pi conjugated polymers. AB - The static longitudinal linear polarizability (alpha) and second order hyperpolarizability (gamma) for neutral and charged, closed- and open-shell trans polyacetylene (PA) chains C(2n)H(2n+2), C(2n-1)H(2n+1), C(2n-1)H(2n+1) (+), C(2n)H(2n+2) (+), and C(2n)H(2n+2) (2+) are systematically investigated and compared. The polarizabilities are calculated within the Pariser-Parr-Pople model, and the electron correlation effect is included through density matrix renormalization group. It turns out that for both alpha, and gamma, two neutral PA chains C(2n)H(2n+2) and C(2n-1)H(2n+1) give similar values, while both singly charged and doubly charged systems present significantly larger magnitude of alpha and gamma values than the two neutral chains. The two singly charged PA chains C(2n-1)H(2n+1) (+) and C(2n)H(2n+2) (+) give more apparent nonlinear optical responses than doubly charged case C(2n)H(2n+2) (2+) and both present negative second order hyperpolarizabilities for short to medium sized oligomers. The sign inversion of gamma values in singly charged PA molecules is anticipated to take place at the much longer length than ever observed due to the significant effects of electron correlation and geometry. PMID- 17286506 TI - Theoretical model based on the memory effect for the strange photoisomerization kinetics of diarylethene derivatives dispersed on polymer films. AB - In the present paper the authors present a theoretical model to explain the kinetics involving the induction period observed by Irie et al. [Nature (London) 420, 759 (2002)] for photoisomerization of diarylethene derivatives dispersed on polymer films at a single molecular level. In the model we assume that both ground state and excited state free energy landscapes which result from the interaction between the photochromic molecule and the surrounding polymer are rugged and have several local minima along the pathway to the critical point at which isomerization actually occurs. We assume that after one photoexcitation a fraction of the photochromic molecule moves to a new local minimum and stays there, although the other fraction returns to the original local minimum. The former effect is referred to as the memory effect. After repeated photoexcitations the photochromic molecule moves gradually from one local minimum to another in the pathway to the isomerization point. It finally reaches the isomerization point, where isomerization occurs. Their model successfully reproduces the kinetics of photoisomerization of diarylethene derivatives dispersed on polymer films observed experimentally. PMID- 17286507 TI - A computer simulation study of the formation of liquid crystal nanodroplets from a homogeneous solution. AB - The aggregation of liquid crystal nanodroplets from a homogeneous solution is an important but not well understood step in the preparation of various advanced photonic materials. Here, the authors performed molecular dynamics computer simulations of the formation of liquid crystalline nanodroplets, starting from an isotropic and uniform binary solution of spherical Lennard-Jones (solvent) and elongated ellipsoidal Gay-Berne (solute) rigid particles in low (<10%) concentration. They studied the dynamics of demixing and the mesogen ordering process and characterized the resulting nanodroplets assessing the effect of temperature, composition, and specific solute-solvent interaction on the morphology, structure, and anisotropy. They find that the specific solute-solvent interaction, composition, and temperature can be adjusted to tune the nanodroplet growth and size. PMID- 17286508 TI - How does the coupling of secondary and tertiary interactions control the folding of helical macromolecules? AB - The authors study how the simultaneous presence of short-range secondary and long range tertiary interactions controls the folding and collapse behavior of a helical macromolecule. The secondary interactions stabilize the helical conformation of the chain, while the tertiary interactions govern its overall three-dimensional shape. The authors have carried out Monte Carlo simulations to study the effect of chain length on the folding and collapse behavior of the chain. They have calculated state diagrams for four chain lengths and found that the physics is very rich with a plethora of stable conformational states. In addition to the helix-coil and coil-globule transitions, their model describes the coupling between them which takes place at low temperatures. Under these conditions, their model predicts a cascade of continuous, conformational transitions between states with an increase in the strength of the tertiary interactions. During each transition the chain shrinks, i.e., collapses, in a rapid and specific manner. In addition, the number of the transitions increases with increasing chain length. They have also found that the low-temperature regions of the state diagram between the transition lines cannot be associated with specific structures of the chain, but rather, with ensembles of various configurations of the chain with similar characteristics. Based on these results the authors propose a mechanism for the folding and collapse of helical macromolecules which is further supported by the analysis of configurational, configurational, and thermodynamic properties of the chain. PMID- 17286509 TI - Numerical study of the gel transition in reversible associating polymers. AB - Four temperatures to characterize the gel transition in reversible associating polymers have been calculated in a novel mixed molecular dynamics/Monte Carlo model. (1) The temperature below which relaxation times no longer show Arrhenius dependence on temperature; (2) the Vogel-Fulcher temperature at which the structural relaxation time extrapolates to infinity; (3) the micelle formation temperature at which the number of reversible bonds sharply increases; and (4) a crossover temperature at which the viscosity exhibits a power law divergence as predicted by mode coupling theory. These specific temperatures are obtained from measurements of diffusivity, specific heat, and network topology. PMID- 17286510 TI - On attractive interaction of a colloid pair of like charge at infinite dilution. AB - Numerical data on the potential of mean force W(r) at infinite dilution of a highly charged colloid pair embedded in a 1:1 electrolyte are reported. The authors obtain attractive minima (W<0) at short interparticle distance in these potential functions in hypernetted chain (HNC) approximation, as salt concentration is increased. These minima, however, disappear in all system sets studied when a self-consistent Zerah-Hansen (ZH) closure is used. The authors infer that the attractive minima obtained in a HNC closure are spurious and result from the neglect of bridge diagrams in HNC approximation. An expression of bridge function, which the ZH closure in effect incorporates in W(r) to remove attractive minima, is derived in terms of modification of correlation functions. Features of repulsive pair potentials obtained using the ZH closure, their dependence on particle charge and salt concentration, and their agreement with those of the Derajguin-Landau-Verwey-Overbeek theory are investigated. PMID- 17286511 TI - Effects of the environmental factors on the casein micelle structure studied by cryo transmission electron microscopy and small-angle x-ray scattering/ultrasmall angle x-ray scattering. AB - Casein micelles are colloidal protein-calcium-transport complexes whose structure has not been unequivocally elucidated. This study used small-angle x-ray scattering (SAXS) and ultrasmall angle x-ray scattering (USAXS) as well as cryo transmission electron microscopy (cryo-TEM) to provide fine structural details on their structure. Cryo-TEM observations of native casein micelles fractionated by differential centrifugation showed that colloidal calcium phosphate appeared as nanoclusters with a diameter of about 2.5 nm. They were uniformly distributed in a homogeneous tangled web of caseins and were primarily responsible for the intensity distribution in the SAXS profiles at the highest q vectors corresponding to the internal structure of the casein micelles. A specific demineralization of casein micelles by decreasing the pH from 6.7 to 5.2 resulted in a reduced granular aspect of the micelles observed by cryo-TEM and the existence of a characteristic point of inflection in SAXS profiles. This supports the hypothesis that the smaller substructures detected by SAXS are colloidal calcium phosphate nanoclusters rather than putative submicelles. PMID- 17286512 TI - Computational spectroscopy of ubiquitin: comparison between theory and experiments. AB - Using the constrained molecular dynamics simulation method in combination with quantum chemistry calculation, Hessian matrix reconstruction, and fragmentation approximation methods, the authors have established computational schemes for numerical simulations of amide I IR absorption, vibrational circular dichroism (VCD), and two-dimensional (2D) IR photon echo spectra of the protein ubiquitin in water. Vibrational characteristic features of these spectra in the amide I vibration region are discussed. From the semiempirical quantum chemistry calculation results on an isolated ubiquitin, amide I local mode frequencies and vibrational coupling constants were fully determined. It turns out that the amide I local mode frequencies of ubiquitin in both gas phase and aqueous solution are highly heterogeneous and site dependent. To directly test the quantitative validity of thus obtained spectroscopic properties, they compared the experimentally measured amide I IR, 2D IR, and electronic circular dichroism spectra with experiments, and found good agreements between theory and experiments. However, the simulated VCD spectrum is just qualitatively similar to the experimentally measured one. This indicates that, due to delicate cancellations between the positive and negative VCD contributions, the prediction of protein VCD spectrum is critically relied on quantitative accuracy of the theoretical model for predicting amide I local mode frequencies. On the basis of the present comparative investigations, they found that the site dependency of amide I local mode frequency, i.e., diagonal heterogeneity of the vibrational Hamiltonian matrix in the amide I local mode basis, is important. It is believed that the present computational methods for simulating various vibrational and electronic spectra of proteins will be of use in further refining classical force fields and in addressing the structure-spectra relationships of proteins in solution. PMID- 17286513 TI - Free energy landscape of receptor-mediated cell adhesion. AB - Receptor-mediated cell adhesion plays a critical role in cell migration, proliferation, signaling, and survival. A number of diseases, including cancer, show a strong correlation between integrin activation and metastasis. A better understanding of cell adhesion is highly desirable for not only therapeutic but also a number of tissue engineering applications. While a number of computational models and experimental studies have addressed the issue of cell adhesion to surfaces, no model or theory has adequately addressed cell adhesion at the molecular level. In this paper, the authors present a thermodynamic model that addresses receptor-mediated cell adhesion at the molecular level. By incorporating the entropic, conformational, solvation, and long- and short-range interactive components of receptors and the extracellular matrix molecules, they are able to predict adhesive free energy as a function of a number of key variables such as surface coverage, interaction distance, molecule size, and solvent conditions. Their method allows them to compute the free energy of adhesion in a multicomponent system where they can simultaneously study adhesion receptors and ligands of different sizes, chemical identities, and conformational properties. The authors' results not only provide a fundamental understanding of adhesion at the molecular level but also suggest possible strategies for designing novel biomaterials. PMID- 17286514 TI - Probing irradiation induced DNA damage mechanisms using excited state Car Parrinello molecular dynamics. AB - Photoinduced proton transfer in the Watson-Crick guanine (G)-cytosine (C) base pair has been studied using Car-Parrinello molecular dynamics (CP-MD). A flexible mechanical constraint acting on all three hydrogen bonds in an unbiased fashion has been devised to explore the free energy profile along the proton transfer coordinate. The lowest barrier has been found for proton transfer from G to C along the central hydrogen bond. The resulting charge transfer excited state lies energetically close to the electronic ground state suggesting the possibility of efficient radiationless decay. It is found that dynamic, finite temperature fluctuations significantly reduce the energy gap between the ground and excited states for this charge transfer product, promoting the internal conversion process. A detailed analysis of the internal degrees of freedom reveals that the energy gap is considerably reduced by out-of-plane molecular vibrations, in particular. Consequently, it appears that considering only the minimum energy path provides an upper-bound estimate of the associated energy gap compared to the full-dimension dynamical reaction coordinate. Furthermore, the first CP-MD simulations of the G-C base pair in liquid water are presented, and the effects of solvation on its electronic structure are analyzed. PMID- 17286515 TI - Simulations of edge behavior in a mixed-lipid bilayer: fluctuation analysis. AB - Coarse-grained molecular dynamics simulations of lipid bilayer ribbons consisting of a mixture of lipids of different tail lengths have been performed to gain insight into bicelle mixtures. The line tension of the bilayer edge decreases as the mole fraction of short-chain lipids in the system is increased, dropping below zero between 30% and 35%. The mole fraction of short-chain lipids in the ribbon interior is lower than the total mole fraction, as the short-chain lipids segregate towards the edge, but continues to rise even after the line tension vanishes, in contrast to predictions of a two-component two-phase model. The fluctuations of the bilayer edge in both high and low line tension regimes have been analyzed to extract information about the factors that influence the length and shape of the edge. At high line tension the wavelength-dependent in-plane fluctuations of the edge are predicted quantitatively using a simple analytical model using only the line tension as input. Where line tension is vanishing, the fluctuations can be modeled as arising from a combination of harmonic fluctuations around a minimum energy contour length and an in-plane bending elasticity. The estimated value of the in-plane bending modulus is of order 10( 29) J m, placing the intrinsic persistence length for the edge near the bilayer thickness of 4 nm. PMID- 17286516 TI - Smart resolution replica exchange: an efficient algorithm for exploring complex energy landscapes. AB - A coarse-grained representation of a condensed phase system can significantly reduce the number of system degrees of freedom, making coarse-grained simulations very computationally efficient. Moreover, coarse graining can smoothen the free energy landscape of the system. Thus coarse-grained dynamics is usually faster than its fully atomistic counterpart. In this work, the smart resolution replica exchange method is introduced that incorporates the information from coarse grained simulations into atomistic simulations in order to accelerate the sampling of rough, complex atomistic energy landscapes. Within this methodology, interactions between particles are defined by a potential energy that interpolates between a fully atomistic potential and a fully coarse-grained effective potential according to a parameter lambda. Instead of exchanging the configurations from neighboring resolutions directly, as has been done in the resolution replica exchange methods [E. Lyman et al., Phys. Rev. Lett. 96, 028105 (2006); M. Christen and W. F. v. Gunsteren, J. Chem. Phys. 124, 154106 (2006)], the configuration described at the coarser resolution is first relaxed before an exchange is attempted, similar to the smart walking method [R. Zhou and B. J. Berne, J. Chem. Phys. 107, 9185 (1997)]. This approach greatly increases the acceptance ratio of exchange and only two replicas, one at the atomistic level and one at the coarse-grained level, are usually required (although more can be implemented if desired). This new method can approximately obtain the correct canonical sampling if the exchange interval is sufficiently large to allow the system to explore the local energy landscape. The method is demonstrated for a two-dimensional model system, where the ideal population distribution can be recovered, and also for an alanine polypeptide (Ala(15)) model with explicit water, where its native structure, an alpha helix, is obtained from the extended structure within 1 ns. PMID- 17286517 TI - Short-time dynamics of polypeptides. AB - The authors study the short-time dynamics of helix-forming polypeptide chains using an all-atom representation of the molecules and an implicit solvation model to approximate the interaction with the surrounding solvent. The results confirm earlier observations that the helix-coil transition in proteins can be described by a set of critical exponents. The high statistics of the simulations allows the authors to determine the exponent values with increased precision and support universality of the helix-coil transition in homopolymers and (helical) proteins. PMID- 17286518 TI - Statistical properties and kinetics of end-end contact formation of unfolded polypeptides: a systematic molecular dynamics study. AB - The authors have systematically examined the statistical properties of the unfolded states of series of polypeptides and the kinetics of their end-to-end contact (ring closure) formation by molecular dynamics simulations. The formation of an end-to-end contact follows a single-exponential decay as measured by the first-passage time. It is shown that the shifted Gaussian chain model can be applied to describe the dimensions of glycine-rich polypeptides at high temperature. However, notable deviation from the ideal Gaussian chain model was observed at lower temperatures particularly for those polypeptides without glycines, due to the tendency to form local structures. PMID- 17286519 TI - Amide I two-dimensional infrared spectroscopy of beta-hairpin peptides. AB - In this report, spectral simulations and isotope labeling are used to describe the two-dimensional IR spectroscopy of beta-hairpin peptides in the amide I spectral region. 2D IR spectra of Gramicidin S, PG12, Trpzip2 (TZ2), and TZ2 T3(*)T10(*), a dual (13)C(') isotope label, are qualitatively described by a model based on the widely used local mode amide I Hamiltonian. The authors' model includes methods for calculating site energies for individual amide oscillators on the basis of hydrogen bonding, nearest neighbor and long-range coupling between sites, and disorder in the site energy. The dependence of the spectral features on the peptide backbone structure is described using disorder-averaged eigenstates, which are visualized by mapping back onto the local amide I sites. beta-hairpin IR spectra are dominated by delocalized vibrations that vary by the phase of adjacent oscillators parallel and perpendicular to the strands. The dominant nu(perpendicular) band is sensitive to the length of the hairpin and the amount of twisting in the backbone structure, while the nu(parallel) band is composed of several low symmetry modes that delocalize along the strands. The spectra of TZ2-T3(*)T10(*) are used to compare coupling models, from which we conclude that transition charge coupling is superior to transition dipole coupling for amide groups directly hydrogen bound across the beta strands. The 2D IR spectra of TZ2-T3(*)T10(*) are used to resolve the redshifted amide I band and extract the site energy of the labeled groups. This allows the authors to compare several methods for calculating the site energies used in excitonic treatments of the amide I band. Gramicidin S is studied in dimethyl sulfoxide to test the role of solvent on the spectral simulations. PMID- 17286520 TI - A common, avoidable source of error in molecular dynamics integrators. PMID- 17286521 TI - Introduction: evaluating the evidence: Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and beyond. PMID- 17286522 TI - The roles of efficacy, safety, and tolerability in antipsychotic effectiveness: practical implications of the CATIE schizophrenia trial. AB - The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) series of studies has set a standard for trials in schizophrenia. Included in the 3-phase National Institute of Mental Health-sponsored series were 1460 patients drawn from 57 sites in 24 states. This was designed as a "real-world" practical clinical trial, including a broad array of patients and asking straightforward, clinically relevant questions. The primary aim was to compare the available atypical agents olanzapine, quetiapine, risperidone, and ziprasidone-to each other and to the typical agent perphenazine-with regard to drug effectiveness and tolerability. In general, the various agents studied were similar, with olanzapine being relatively the most effective, as measured by treatment discontinuation. This might be due in part to the more optimal dosing of olanzapine compared with the other antipsychotics. In the study arm that included clozapine, that agent was shown to be more effective than olanzapine, quetiapine, or risperidone. Perphenazine tended to perform as well as the atypical agents. Except for clozapine, olanzapine clearly had the greatest metabolic side effect burden, and ziprasidone, the least. Perphenazine had the most motor side effects, although the rate was modest. PMID- 17286523 TI - Discontinuing and switching antipsychotic medications: understanding the CATIE schizophrenia trial. AB - A new standard in effectiveness research on schizophrenia medications has been established by the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. The study used an innovative approach to determining relative effectiveness of medications by using time until medication discontinuation or switch as the primary outcome criterion. The study is perhaps best known for the overall high proportion of subjects (74%) meeting all-cause discontinuation (ACD) criteria within the 18-month time frame of being assigned to their phase 1 antipsychotic. However, some of the drawbacks of the ACD approach are not well understood, in part because of unfamiliarity with the way ACD was assessed and problems with the use of hierarchical criteria to establish the primary reason for medication discontinuation. Using the time until ACD as an endpoint cannot by itself capture the complexity of the trajectory of a patient's response to a new medication. In particular, it is quite plausible that switching medications upon entering CATIE phase 1 would reduce some symptoms, which then would lead to a greater desire to make another medication switch. Using ACD criteria, a comparison with CATIE subjects who coincidentally remained on treatment with their preswitch medication would make it seem that switching was detrimental when in fact it could have been helpful. Another major limitation of the ACD was omitting the recording of the reason for stopping study medication whenever the ACD was considered to be a "patient-decision" discontinuation. This means that patient-initiated discontinuations could never be classified as a tolerability discontinuation. Since the ACD was done by the patients' clinicians, this approach may have underestimated the proportion of side effect discontinuations whenever the patient disagreed with his or her clinician. Moreover, retaining the "patient-decision" discontinuation subgroup in the attributable risk estimates of tolerability discontinuations further minimizes the attributable risk estimate of the role of side effects relative to other causes of discontinuation. For these assumptions to be valid would require the very optimistic assumption that CATIE clinicians never underestimated tolerability concerns in their patients. Otherwise, this mutually exclusive approach will lead to significant underestimation of the proportion of CATIE discontinuations caused by tolerability problems. It can be argued that excluding the "patient decision" subgroup from the attributable risk estimate of role of tolerability in medication discontinuation is a better approach to mitigate against these biases. A reanalysis using an adjusted N of 1061 evaluable subjects changes the attributable portion of tolerability discontinuations from 14.9% to 38.5%. Regarding specific side effect-medication pairs of interest, the attributable risk of extrapyramidal symptoms as a reason for discontinuing perphenazine increases from 8% to 21%, and weight-related discontinuations from olanzapine from 9% to 28%. Therefore, the clinical implications of the CATIE phase 1 findings may depend, in part, on the underlying assumptions of the ACD outcome measure. PMID- 17286524 TI - Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. AB - Compared with the general population, persons with schizophrenia have up to a 20% shorter lifespan, with cardiovascular disease as the leading cause of death. In addition, persons with schizophrenia have increased prevalence of the metabolic syndrome (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), increased prevalence of risk factors such as smoking, poverty, and poor nutrition, and reduced access to medical care. Results from the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) provide further evidence of the metabolic risk associated with different atypical antipsychotics. Based on this study and a growing number of other randomized clinical trials, clozapine and olanzapine treatment can produce substantial mean changes in weight and an increased risk of associated metabolic disturbances. Risperidone and quetiapine treatment can produce intermediate changes in mean weight in comparison to treatment with other atypical antipsychotics, with discrepant results with respect to metabolic risk. Aripiprazole and ziprasidone treatment induced the lowest mean changes in weight gain and had no effect on risk for adverse metabolic changes, among currently available atypical agents. Considerable evidence indicates that mentally ill patients often do not receive adequate recognition of, monitoring of, or care for their medical illnesses. There is a critical need for psychiatrists and primary care professionals to increase awareness of and attention to the physical health problems of persons with mental illness, including appropriate management of metabolic adverse events associated with psychiatric medications. PMID- 17286525 TI - Strategies for the long-term treatment of schizophrenia: real-world lessons from the CATIE trial. AB - Patients with schizophrenia have a chronic illness necessitating a biopsychosocial model of care that addresses the multiple dimensions of the disease, including coordinated primary care. Current research, including the lessons learned from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, shows that in addition to education, adherence, and minimizing adverse effects of psychopharmacologic agents, multimodal long-term treatment strategies are needed to address medical comorbidities, substance abuse, and both cognitive and social deficits. Health care professionals have the responsibility to monitor and help prevent adverse medical outcomes related to treatment with antipsychotics, in light of evidence that patients with schizophrenia are at risk for metabolic disorders and are undertreated for highly prevalent cardiovascular risk factors. These medical problems are particularly challenging in this population due to the chronicity of symptoms, cognitive limitations, social and financial challenges, and compliance issues with recommended medication treatment and therapeutic lifestyle changes. Mental health providers in the United States are now studying models that support the integration of psychiatric and nonpsychiatric medical treatment to address the complexity of multimodal schizophrenia care. PMID- 17286526 TI - Minor depression and health status among US adults with diabetes mellitus. AB - OBJECTIVE: To determine whether diabetes mellitus (DM) with minor depression is associated with poorer levels of mental and physical functioning compared with DM without depression. STUDY DESIGN: Retrospective database study. METHODS: US adults participating in the 2001 Medical Expenditure Panel Survey were included in these analyses. Main outcome measures were differences in health status, physical and cognitive limitations, and the Short-Form 12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS) for US adults with DM stratified by minor depression status and evaluated using univariate and multivariate analyses to control for demographic, behavioral, and clinical covariates. RESULTS: A total of 1572 respondents with DM were included (1443 without depression, 129 with depression). Compared with people with DM and without depression, those with DM and minor depression were younger (P = .04); were more likely to be female, white, and smokers; and to have physical and cognitive limitations and lower SF-12 MCS and PCS scores (all P < .01). In multivariate analyses, minor depression was independently associated with lower self-reported health status, MCS scores, and more cognitive limitations. CONCLUSION: People with DM and minor depression have lower mental functional scores, more cognitive limitations, and lower self-reported health status scores compared with people with DM and without depression, differences that may adversely affect self-care activities. Primary and DM care providers should screen for and be aware of depression in their patients with DM. PMID- 17286527 TI - Facility variation in utilization of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with diabetes mellitus and chronic kidney disease. AB - OBJECTIVE: To evaluate facility-level variation in prescription rates of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) medications for patients with diabetes mellitus (DM) and chronic kidney disease (CKD). STUDY DESIGN: Retrospective database analysis from 143 Veterans Health Administration facilities. METHODS: Subjects with DM aged 18 to 75 years were identified as having stage 2-4 CKD using estimated glomerular filtration rate (eGFR) based on an index eGFR in 1999 and a subsequent eGFR 90-365 days later. Whether ACEI/ARB medications were prescribed within 1 year after the index eGFR was determined. Variation in facility-level rates was evaluated separately for subjects age <65 years and 65 to 75 years from facilities with more than 50 subjects per age group. RESULTS: A total of 103 853 subjects had stage 2 CKD; 51 728, stage 3; and 3233, stage 4. However, 25% of facilities had fewer than 50 patients age <65 years with either stage 3 or 4 CKD. The median (range) facility level prescription rates of ACEI/ARB for stage 2 and combined stage 3-4 CKD were 58.5% (44.3%-71.2%) and 73.3% (51.7%-84.6%), respectively, for subjects age <65 years; and 56.5% (38.1%-71.4%) and 68.4% (51.6%-80.1%), respectively, for subjects aged 65 to 75 years. Spearman rank correlation between facility rankings by age group was 0.72 for stage 2 (139 facilities) and 0.49 for stage 3-4 (111 facilities) (P < .001). CONCLUSION: Although ascertainment of prescription rates of ACEI/ARB to CKD patients is feasible using electronic health records, small sample size at the healthcare-system level preclude their utility for public reporting. PMID- 17286528 TI - Patient-centered management of complex patients can reduce costs without shortening life. AB - OBJECTIVE: To determine the effect of intensive patient-centered management (PCM) on service utilization and survival. STUDY DESIGN: Prospective cohort study of 756 patients in California who had a life-limiting diagnosis with multiple comorbid conditions (75% were oncology patients) and who were covered by a large commercial health maintenance organization from February 2003 through December 2004. METHODS: Group membership determined assignment to the PCM cohort versus the usual-management cohort after blindly screening for clinical complexity. Both cohorts accessed the same delivery system, utilization management practices, and benefits. Intervention was intensive PCM, involving education, home visits, frequent contact, and goal-oriented care plans. RESULTS: Roughly half (358) of the 756 patients received PCM. Fewer PCM oncology patients elected either chemotherapy or radiation (42% increase over usual-management oncology patients). PCM patients had reductions in inpatient diagnoses indicative of uncoordinated care: nausea (-44%), anemia (-33%), and dehydration (-17%). PCM patients had utilization reductions: -38% inpatient admissions (95% confidence interval [CI] = -37%, -38%), -36% inpatient hospital days (95% CI = -35%, -37%), and -30% emergency department visits (95% CI = -29%, -31%). PCM patients had utilization increases: 22% more home care days (95% CI = 20%, 23%) and 62% more hospice days (95% CI = 56%, 67%). Overall costs were reduced by 26% (95% CI = 25%, 27%). Patients' lives were not shortened (26% of PCM patients died vs 28% of patients who received usual management) (P = .80). CONCLUSION: Comprehensive PCM can sharply reduce utilization and costs over usual management without shortening life. PMID- 17286529 TI - Reducing the number of emergency department visits and costs associated with anxiety: a randomized controlled study. AB - OBJECTIVE: To demonstrate the economic effects of an intervention for members discharged from the emergency department (ED) with anxiety diagnoses. STUDY DESIGN: Randomized controlled study. METHODS: Adults with commercial, Medicare, or Medicaid insurance coverage enrolled in a health maintenance organization and discharged from an ED with anxiety diagnoses were randomly assigned to receive usual care (n = 300) or a stepped-care intervention (n = 307). Psychiatric ED and outpatient visit utilization and cost data identified by claims were collected for 6 months following the initial ED visit. RESULTS: Members assigned to receive the intervention demonstrated significantly fewer ED visits and lower associated facility costs in the 6 months following discharge compared with those assigned to usual care. No significant differences in psychiatric outpatient visit costs were observed. Members receiving usual care made 117 visits to the ED for a psychiatric condition during the follow-up period, for a mean of 0.39 visits per member and a mean facility cost of 118.15 dollars per member, while members receiving case management services made 79 visits to the ED for a psychiatric condition during the follow-up period, for a mean of 0.26 visits per member and a mean facility cost of 70.63 dollars per member. The intervention resulted in a savings of 7.92 dollars in ED costs per member per month for all psychiatric diagnoses during the 6-month study period. CONCLUSION: The case management-based intervention effectively reduced psychiatric ED recidivism and costs for members discharged from the ED with an anxiety diagnosis, without significantly affecting psychiatric outpatient visit costs. PMID- 17286530 TI - The association of antidepressant medication adherence with employee disability absences. AB - OBJECTIVE: To evaluate the relationship between antidepressant medication adherence and short-term disability (STD) in an employed population. STUDY DESIGN: Retrospective observational cohort study of 2112 employees with a new episode of treatment with an antidepressant medication (selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors). METHODS: Both Health Plan Employer Data and Information Set (HEDIS) acute and continuation treatment guidelines were applied to categorize patients' medication adherence. STD events were followed for 365 days after the date that an initial antidepressant medication prescription was filled. The association between STD and adherence was analyzed with multiple logistic regression models, adjusting for demographic and other confounding factors. RESULTS: A total of 1301 employees (61.6% of 2112) adhered to acute phase treatment, and 966 (45.7% of 2112) remained adherent to continuation phase treatment. After adjusting for sociodemographic factors, employees nonadherent with acute treatment were 38.7% more likely to have STD claims than adherent employees (odds ratio [OR] = 1.387; 95% confidence interval [CI] = 1.025, 1.876; P = .0339); and employees nonadherent with continuation treatment were 46.1% more likely to have STD claims than adherent employees (OR = 1.461; 95% CI = 1.071, 1.993; P = .0167). CONCLUSIONS: A higher incidence of STD was associated with antidepressant medication nonadherence in both acute and continuation treatment phases. Employers may save indirect costs by providing assistance to encourage employees to adhere to their antidepressant medication treatment. PMID- 17286531 TI - Heat shock protein-receptor-based pharmacogenomics: the search for new cancer antigens. PMID- 17286532 TI - Nutrigenomics and the prevention of colon cancer. PMID- 17286533 TI - Unraveling hypertension: epigenomics comes of age. PMID- 17286534 TI - Gene-expression profiling in lung cancer: still early days. PMID- 17286536 TI - The diverse and informative future of microarray applications. PMID- 17286537 TI - Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients. AB - The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. The glutamates are released from MTX by activity of the enzyme gamma-glutamyl-hydrolase (GGH), thereby allowing the efflux of MTX. GGH 452C>T has been associated with decreased catalytic activity and higher accumulation of long-chain MTX-polyglutamate. However, single nucleotide polymorphisms (SNPs) in FPGS and GGH genes have not yet been explored for association with MTX efficacy or toxicity. We selected for SNPs with frequencies higher than 10% or, in case of FPGS 114G>A, causing an amino acid change with no known frequencies. In this study, frequencies of two SNPs in FPGS (1994A>G and 114G>A, rs10106 and rs10760502, respectively) and GGH genes (452C>T and 16T>C, rs11545078 and rs1800909, respectively), were determined using a newly developed method in rheumatoid arthritis patients (n = 352) and in a group of healthy controls (n = 360). Next, the SNPs were associated with response to MTX in rheumatoid arthritis patients treated with MTX monotherapy. In rheumatoid arthritis patients, allele frequencies of FPGS 1994A>G were 0.534 (A) and 0.466 (G), and for FPGS 114G>A 0.714 (G) and 0.286 (A). Allele frequencies of GGH 16T>C were 0.737 (T) and 0.263 (C) and for GGH 452C>T 0.912 (C) and 0.088 (T). No significant differences in allele frequencies between rheumatoid arthritis patients and healthy controls were found. In addition, the SNPs were not associated with good clinical response to MTX. Only patients with the GGH 16C allele and one or no copies of the GGH 452C-16T haplotype were associated with good clinical improvement at 3 months upon treatment with MTX. No associations with efficacy at 6 months and MTX-induced toxicity were found. Therefore we conclude that despite the positive association of the GGH 16C-allele and one or no copies of the GGH 452C-16T haplotype with good clinical improvement at 3 months upon treatment with MTX, the tested SNPs in GGH and FPGS genes are suggested not to be clinically important for MTX treatment outcome. PMID- 17286538 TI - CYP2A6 polymorphisms: is there a role for pharmacogenomics in preventing coumarin induced hepatotoxicity in lymphedema patients? AB - Lymphedema is a chronic progressive and significantly disabling disease that affects over 150 million people worldwide. Coumarin is an effective pharmacological treatment, but is banned in some countries due to incidences of hepatotoxicity in rats and mice, and the rare finding of similar hepatotoxicity in humans. Cytochrome P450 (CYP)2A6 is the major enzyme involved in metabolizing coumarin to 7-hydroxycoumarin. A reduction in CYP2A6 activity will lead to shunting of coumarin into other metabolic pathways. In particular, coumarin is metabolized by CYP3A4 to form 3-hydroxycoumarin, the major metabolite in mice and rats. It has been shown that an increase in the 3-hydroxycoumarin ratio is associated with an increased production of the significant cytotoxic product o hydroxyphenylacetylacetaldehyde (o-HPA), suggesting that a shunting of coumarin metabolism away from 7-hydroxylation is the cause of the toxicity. Hence, poor CYP2A6 metabolizers are more likely to metabolize coumarin via the cytotoxic pathway. Identifying these patients, and not treating them with coumarin, may reduce the incidence of toxicity associated with this drug. The technology to do so exists, but more information is required regarding the mechanism of coumarin toxicity. PMID- 17286539 TI - Pharmacogenetics of antiparkinsonian drug treatment: a systematic review. AB - Pharmacotherapy is the mainstay in the treatment of Parkinson's disease and the armamentarium of drugs available for the therapy of this disease is still expanding. Anti-Parkinson's disease drugs are effective in reducing the physical symptoms, such as hypokinesia, bradykinesia, rigidity and tremor. However, there is a large interindividual variability in response to anti-Parkinson's disease drugs with respect to both drug efficacy and toxicity. It is thought that genetic variability in genes encoding drug-metabolizing enzymes, drug receptors and proteins involved in pathway signaling is an important factor in determining interindividual variability in drug response. Pharmacogenetics aims at identifying genetic markers associated with drug response. Ideally, knowledge of these genetic markers will enable us to predict an individual's drug response in terms of both efficacy and toxicity. The role of pharmacogenetics in the treatment of Parkinson's disease is relatively unexplored. Therefore, we aim to present a systematic review of the published pharmacogenetic studies in Parkinson's disease and to describe polymorphic genes of interest for future research. PMID- 17286540 TI - Mapping translational research in personalized therapeutics: from molecular markers to health policy. AB - Translational research is frequently used in the bioscience literature to refer to the translation of basic science into practical applications at the point of patient care. With the introduction of theragnostics, a new medical subspecialty that fuses therapeutics and diagnostic medicine with the goal of providing individualized pharmacotherapy, we suggest that the focus of translational research is shifting. We identify two bottlenecks or gaps in translational research for theragnostics: GAP1 translation from basic science to first-in-human proof-of-concept; and GAP2 translation from clinical proof-of-concept to development of evidence-based personalized treatment guidelines. GAP1 translational research in theragnostics is usually performed in traditional craft based studies with small sample sizes and led by independent academic or industry researchers. In contrast, GAP2 translational investigations typically rely on large research consortiums and population-based biobanks that couple biomarker information with longitudinal 'real-life' observational data on a broad range of pharmacological phenotypes. Despite an abundance of research on the use of biobanks in disease gene discovery, there has been little conceptual work on whether and to what extent population biobanks can be utilized for translating genomics discoveries to practical treatment guidelines for theragnostic tests. PMID- 17286541 TI - CYP2C8 and antimalaria drug efficacy. AB - Malaria is a major infectious disease. In the last 10 years it has killed more than 20 million people, mainly small children in Africa. The highly efficacious artemisinine combination therapy is being launched globally, constituting the main hope for fighting the disease. Amodiaquine is a main partner in these combinations. Amodiaquine is almost entirely metabolized by the polymorphic cytochrome P450 (CYP) isoform 2C8 to the pharmacologically active desethylamodiaquine. The question remains whether the efficacy of amodiaquine is affected by the gene polymorphism. Genotype-inferred low metabolizers are found in 1-4% of African populations, which corresponds to millions of expected exposures to the drug. In vivo pharmacokinetic data on amodiaquine is limited. By combining it with published in vitro pharmacodynamic and drug metabolism information, we review and predict the possible relevance, or lack of, of CYP2C8 polymorphisms in the present and future efficacy of amodiaquine. Chloroquine and dapsone, both substrates of CYP2C8, are also discussed in the same context. PMID- 17286543 TI - Anxiety sensitivity: selective review of promising research and future directions. PMID- 17286545 TI - Paroxetine: current status in psychiatry. AB - Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with antidepressant and anxiolytic properties. It is commercially available in both an immediate release (paroxetine) and a controlled-release formulation (paroxetine CR). The latter product was developed to improve gastrointestinal tolerability. Paroxetine is the most potent inhibitor of the reuptake of serotonin among the available SSRIs. It has approved indications for the treatment of major depression, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, post traumatic stress disorder and social phobia in adults. Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults. While the overall efficacy of paroxetine appears to be comparable with other SSRIs in the treatment of major depression, it is approved for use in a wider variety of anxiety disorders than any other antidepressant. Long-term data suggest that paroxetine is effective in preventing relapse or recurrence of depression for up to 1 year. Limited data show that paroxetine maintains a therapeutic response over 1 year in obsessive compulsive disorder and up to 6 months in panic disorder. The side-effect profile of paroxetine is largely similar to that of the other SSRIs, although paroxetine tends to be more sedating and constipating in some patients, perhaps due to its anticholinergic activity. The potential for discontinuation syndrome and weight gain appears to be slightly higher with paroxetine than with other SSRIs. This review focuses on the immediate release and controlled-release formulations of paroxetine. It summarizes the efficacy and tolerability data for both formulations, with a particular emphasis on paroxetine CR which was introduced in 2002. It also discusses emerging evidence in other clinical areas and recent data that have led to modifications in the safety profile of paroxetine. PMID- 17286546 TI - Varenicline for smoking cessation. AB - Varenicline is a selective alpha(4)beta(2) nicotinic acetylcholine receptor partial agonist and the first non-nicotine-containing medication developed with the sole purpose of treating nicotine addiction. To date, four published clinical trials have demonstrated the efficacy and safety of varenicline for smoking cessation in healthy adults who were ready to make a quit attempt. One additional trial found that extended use of varenicline effectively reduced relapse to smoking. One trial to date published as a poster documented the 1-year safety of the drug. Varenicline was more efficacious than bupropion 24 weeks after randomization to a 12-week treatment course and 1 year after randomization in an identical trial. It has no contraindications except hypersensitivity and is well tolerated. This article reviews the available information on varenicline and discusses its clinical use. PMID- 17286547 TI - Physiological evaluation of psychological treatments for anxiety. AB - Classification of mental disorders has been greatly influenced by a medical model postulating biological abnormalities that underlie its divisions. Particularly in anxiety disorders, physiological symptoms are part of the Diagnostic and Statistical Manual criteria. Therefore, successful therapy should influence physiological as well as cognitive-verbal expressions of anxiety. Nevertheless, despite the well-known limitations of self-report, physiological outcome measures have only occasionally been employed. We searched the literature for treatment studies that attempted to make a physiological argument for the efficacy of a psychological treatment for anxiety. Our search found only a few methodologically sound examples, where normalization of self-report and physiological measures corresponded. The most convincing studies dealt with the treatment of specific phobias and post-traumatic stress disorder. PMID- 17286548 TI - Endovascular management of acute ischemic stroke: advances in patient and treatment selection. AB - Selection of patients for acute-stroke therapy has traditionally been based on rigid time criteria in clinical trials. Recent advances in radiographic imaging have allowed clinicians to estimate brain physiology and thus utilize radiographic parameters to select patients for acute-stroke therapies. Both a better understanding and the quantification methods of salvageable tissue versus irreversibly injured tissue can help guide clinicians to which treatment modality to utilize. The evolution of endovascular techniques to treat acute stroke has resulted in treatment modalities that include mechanical and chemical methods to revascularize occluded cerebral arteries. Prior technical limitations to accessing distal-cerebral arteries have been partially overcome by modifications in technology. Patient and treatment-modality selection can help reduce hemorrhagic complication rates and also potentially increase revascularization rates, which may translate into improved clinical outcomes. We review the recent advances in radiographic imaging that have advanced patient selection in treating acute ischemic stroke and also consider current endovascular treatment options that are available to interventionalists performing these procedures. PMID- 17286550 TI - New advances in the rehabilitation of CNS diseases applying rTMS. AB - Transcranial magnetic stimulation (TMS) can directly stimulate the CNS, modifying the brain's plasticity to enhance the behavior of the paretic extremities. Studies with low-frequency repetitive TMS (rTMS) on the intact hemisphere and those with high frequencies on the affected hemisphere could increase the speed of movement in the hand affected by CNS injury. Stimulation of the motor pathway may contribute to faster improvement in patients with spinal cord injury. Symptoms of Parkinson's disease (such as cognition and working memory, neglect syndrome and global aphasia) can be influenced by rTMS. However, the site of stimulation and the parameters of rTMS are different. Processes that contribute to the behavior of rTMS include the modification of brain plasticity, induction of neurogenesis, growth of new fibers in the spinal cord or all of these together. According to previous research, rTMS may be suitable as an add-on therapy to rehabilitation in CNS diseases. PMID- 17286549 TI - Therapeutic hypothermia in acute ischemic stroke. AB - Increased body temperatures are common in the acute phase of stroke. Experimental and clinical studies have suggested that increased body temperatures are related to poor outcome. In animal studies of focal cerebral ischemia, early hypothermia consistently reduced infarct volume. Based on these findings, several Phase II clinical trials have been performed to study physical methods to reduce body temperature in patients with acute stroke. The feasibility and safety of these methods have not yet been established with sufficient certainty. Pharmacological lowering of body temperature may be an attractive alternative approach. In guidelines for the treatment of acute stroke, antipyretics are generally recommended to reduce fever, although their effect on functional outcome is unknown. There is currently no evidence from randomized trials to support routine use of physical or pharmacological cooling in acute stroke. Large randomized clinical trials are needed to study the effect of both physical and medical cooling on functional outcome after stroke. PMID- 17286551 TI - Antiepileptic drug treatment in children. AB - Epilepsy is one of the most common neurological disorders of childhood, and antiepileptic drugs represent the main component of its treatment. The current emphasis in epilepsy treatment is to improve quality of life, not only by suppressing seizure, but also by minimizing the side effects of medications. The last 15 years have been characterized by significant advances in the development of new agents that have helped us to get closer to this goal. Knowledge of the essential properties, key indications and interactions of each antiepileptic drug will help to optimize efficacy and reduce adverse reactions. Age is also a determining factor of the epilepsy phenotype and its treatment. This review addresses the principles of pediatric epilepsy treatment, summarizes the profile of each of the commonly used antiepileptic drugs, and provides a treatment paradigm for particular seizures and epilepsy syndromes of childhood. PMID- 17286552 TI - Pharmacotherapy of attention-deficit/hyperactivity disorder: nonstimulant medication approaches. AB - Attention-deficit/hyperactivity disorder (ADHD) is one of the most common chronic health conditions and mental disorders affecting school-aged children. Prevalence with a conservative estimate is reported to be 3-5% of this population. Boys are approximately three-times more likely to be diagnosed than girls. The diagnosis refers to a family of related chronic neurobiological disorders that interfere with an individual's capacity to regulate activity level, inhibit behavior and attend to tasks in developmentally appropriate ways. Signs and symptoms of ADHD are typically present during the preschool period or in the early elementary school years, and the diagnosis requires that difficulties were present at or before age 7 years and create problems or impairment in at least two areas of the child's life (e.g., at school, on the playground, on the bus, at home or socially with peers). Stimulants are the first-line medication in the psychopharmacological treatment of ADHD. Between 10 and 30% of those affected with ADHD may not respond to stimulants or may not be able to tolerate associated side effects, such as appetite suppression, sleep disturbance, mood difficulties or exacerbation of comorbid tic disorders. In such instances, or when families are unwilling to consider a stimulant, nonstimulant medications may be appealing. Several nonstimulant medications that affect noradrenergic and/or dopaminergic pathways have demonstrated efficacy in the treatment of ADHD, although effect sizes are comparable with methylphenidate, fewer data have accumulated regarding the safety profile of nonstimulants in general. This review focuses on etiology, assessment and treatment of ADHD, in particular alternative treatment approaches with various nonstimulant agents, especially atomoxetine. PMID- 17286553 TI - Emerging treatments for major depression. AB - Antidepressant drugs were introduced into clinical practice in the mid-20th Century. While for the most part they have proven effective for the amelioration of depressive symptoms, they are associated with significant deficiencies. These well-recognized shortcomings have given impetus to the pursuit of new molecules that seek to improve on the efficacy, tolerability and safety of existing medications. The following article reviews several new compounds that may have antidepressant potential. Some are more advanced in development, having undergone clinical trials, whereas the clinical potential of others is yet to be explored. For this latter group of compounds, the antidepressant potential relies on their activity in validated animal models. Agomelatine and duloxetine are in the first category, having shown antidepressant efficacy in clinical trials. The blockade of cortisol secretion continues to be a focus of attention for the development of new antidepressants. Thus, synthesis inhibitors, nonpeptide antagonists of corticotropin-releasing factor and glucocorticoid receptor antagonists show some promise in clinical and preclinical tests. Antagonists of the neuropeptide substance P, vasopressin and neuropeptide Y represent a departure of approach from traditional monoamine receptor-based mechanisms. While the clinical results with one substance P antagonist have led to the cessation of further trials, other molecules are in development. Approaches to treatment based on glutamatergic transmission arose from observations in animal models. The clinical evaluation of such compounds awaits further development. The extent to which new agents can be judged to have met the goals of efficacy, tolerability and safety rely not only acute treatment trials but also on longer-term outcomes and postmarketing surveillance. Whether any of the new agents canvassed here prove to be significantly better than existing agents is clearly a judgement for the future. PMID- 17286554 TI - Phage passage after extended processing in small-virus-retentive filters. AB - Retention of a two small phages (PhiX-174 and pp7) by direct-flow small-virus retentive filters [Viresolve NFP (normal-flow parvovirus), Virosart CPV (canine parvovirus), Ultipor DV20 and Planova 20N] was studied using a commercial-process fluid. Phage passage occurred in each filter type, particularly when overloaded with phage. Clearances of pp7 and PhiX-174 were similar for any given filter brand, arguing that the two phages are equivalent for testing small-virus retentive filters. The patterns of flux under constant pressure and instantaneous LRV (log reduction value) in relationship to cumulative phage load differed between brands, consistent with the current industry understanding that each brand possesses specific performance attributes. Phages are a powerful and universal tool for evaluating filter performance. Validation of filter performance with phages such as pp7 or PhiX-174 as models for small mammalian viruses represents an attractive alternative to the current practice. PMID- 17286555 TI - Characterization of novel non-nucleoside reverse transcriptase (RT) inhibitor resistance mutations at residues 132 and 135 in the 51 kDa subunit of HIV-1 RT. AB - Several rare and novel NNRTI [non-nucleoside reverse transcriptase (RT) inhibitor] resistance mutations were recently detected at codons 132 and 135 in RTs from clinical isolates using the yeast-based chimaeric TyHRT (Ty1/HIV-1 RT) phenotypic assay. Ile132 and Ile135 form part of the beta7-beta8 loop of HIV-1 RT (residues 132-140). To elucidate the contribution of these residues in RT structure-function and drug resistance, we constructed twelve recombinant enzymes harbouring mutations at codons 132 and 135-140. Several of the mutant enzymes exhibited reduced DNA polymerase activities. Using the yeast two-hybrid assay for HIV-1 RT dimerization we show that in some instances this decrease in enzyme activity could be attributed to the mutations, in the context of the 51 kDa subunit of HIV-1 RT, disrupting the subunit-subunit interactions of the enzyme. Drug resistance analyses using purified RT, the TyHRT assay and antiviral assays demonstrated that the I132M mutation conferred high-level resistance (>10-fold) to nevirapine and delavirdine and low-level resistance (approximately 2-3-fold) to efavirenz. The I135A and I135M mutations also conferred low level NNRTI resistance (approximately 2-fold). Subunit selective mutagenesis studies again demonstrated that resistance was conferred via the p51 subunit of HIV-1 RT. Taken together, our results highlight a specific role of residues 132 and 135 in NNRTI resistance and a general role for residues in the beta7-beta8 loop in the stability of HIV-1 RT. PMID- 17286557 TI - Use of eyedrops in glaucoma: how can we help to reduce non-compliance? PMID- 17286558 TI - Gene expression profiling of the pH response in Shigella flexneri 2a. AB - The pH response of Shigella flexneri 2a 301 was identified by gene expression profiling. Gene expression profiles of cells grown in pH 4.5 or 8.6 were compared with the profiles of cells grown at pH 7.0. Differential expression was observed for 307 genes: 97 were acid up-regulated, 102 were acid down-regulated, 91 were base up-regulated, and 86 were base down-regulated. Twenty-seven genes were found to be both acid and base up-regulated, and 29 genes were both acid and base down regulated. This study showed that (1) the most pH-dependent genes regulate energy metabolism; (2) the RpoS-dependent acid-resistance system is induced, while the glutamate-dependent acid resistance system is not; (3) high pH up-regulates some virulence genes, while low pH down-regulates them, consistent with Shigella infection of the low gut; and (4) several cross-stress response genes are induced by pH changes. These results also illustrate that many unknown genes are significantly regulated under acid or basic conditions, providing researchers with important information to characterize their function. PMID- 17286556 TI - Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes. AB - Adiponectin is intimately involved in the regulation of insulin sensitivity, carbohydrate and lipid metabolism, and cardiovascular functions. The circulating concentration of adiponectin is decreased in obesity and Type 2 diabetes. The present study attempts to elucidate the mechanisms underlying the regulation of adiponectin secretion and expression in rat primary adipocytes. The beta-agonist, isoprenaline, decreased adiponectin secretion and expression in a dose-dependent manner in primary adipocytes. Importantly, such an inhibitory effect could be blocked by insulin. The opposing effects of isoprenaline and insulin could be explained by differential regulation of intracellular cAMP levels, since cAMP analogues suppressed adiponectin secretion and expression in a fashion similar to isoprenaline, and insulin blocked the inhibitory effects of the cAMP analogue hydrolysable by PDE (phosphodiesterase). A specific PDE3 inhibitor, milrinone, and PI3K (phosphoinositide 3-kinase) inhibitors abolished the effects of insulin on adiponectin secretion and expression. In the same studies, leptin secretion and expression displayed a similar pattern of regulation to adiponectin. We conclude that insulin and beta-agonists act directly at the adipocytes in opposing fashions to regulate the production of adiponectin and leptin, and that a PI3K-PDE3B-cAMP pathway mediates the effects of insulin to restore beta agonist/cAMP-suppressed secretion and expression of these two adipokines. PMID- 17286559 TI - Ogataea thermophila sp. nov., the teleomorph of Candida thermophila. AB - Ascospore formation was observed in the type strain of Candida thermophila Shin K S, Shin YK, Yoon and Park on some yeast sporulation media. In addition, a further sporulating strain was found that proved to be conspecific with C. thermophila on the basis of sequences of the D1/D2 domain of the large-subunit (26S) rRNA gene and the internal transcribed spacer (ITS)1-5.8S rRNA gene - ITS2 region. Therefore, Ogataea thermophila Peter, Tornai-Lehoczki, Shin K-S & Dlauchy sp. nov. is proposed as the teleomorph of C. thermophila. The type strain is Y94(T)=JCM 10994(T)=KCCM 50661(T)=KCTC 17233(T). PMID- 17286560 TI - The F1-ATPase inhibitor Inh1 (IF1) affects suppression of mtDNA loss-lethality in Kluyveromyces lactis. AB - Loss of mtDNA by the petite-negative yeast Kluyveromyces lactis is lethal (rho(o) lethality). However, mutations in the alpha, beta and gamma subunits of F(1) ATPase can suppress lethality by increasing intramitochondrial hydrolysis of ATP. Increased hydrolysis of ATP can also occur on inactivation of Inh1, the natural inhibitor of F(1)-ATPase. However, not all strains of K. lactis show suppression of rho(o)-lethality on inactivation of INH1. Genetic analysis indicates that one or more alleles of modifying factors are required for suppression. Papillae showing enhanced resistance to ethidium bromide (EB) in INH1 disruptants have mutations in the alpha, beta and gamma subunits of F(1)-ATPase. Increased growth of double mutants on EB has been investigated by disruption of INH1 in previously characterized atp suppressor mutants. Inactivation of Inh1, with one exception, results in better growth on EB and increased F(1)-ATPase activity, indicating that suppression of rho(o)-lethality is not due to atp mutations preventing Inh1 from interacting with the F(1)-complex. By contrast, in suppressor mutants altered in Arg435 of the beta subunit, disruption of INH1 did not change the kinetic properties of F(1)-ATPase or alter growth on EB. Consequently, Arg435 appears to be required for interaction of Inh1 with the beta subunit. In a previous study, a mex1-1 allele was found to enhance mgi(atp) expression. In accord with results from double mutants, it has been found that mex1-1 is a frameshift mutation in INH1 causing inactivation of Inh1p. PMID- 17286561 TI - Indole-3-acetic acid enhances the biocontrol of Penicillium expansum and Botrytis cinerea on pear fruit by Cryptococcus laurentii. AB - This study evaluated the efficacy of indole-3-acetic acid (IAA) alone or with a biocontrol yeast, Cryptococcus laurentii, in the inhibition of blue and gray mold diseases (Penicillium expansum and Botrytis cinerea) on pear fruit. The results demonstrated that a combination of C. laurentii with IAA at 100 microg mL(-1) was more effective in suppressing blue and gray mold infections on pear fruit than application of C. laurentii alone. IAA alone or with C. laurentii stimulated catalase, peroxidase and polyphenol oxidase activities of pear fruit, indicating that IAA can induce fruit-mediated resistance, although this agent alone had no direct antifungal activity. PMID- 17286562 TI - Induction of apoptosis in Vero cells by Aeromonas veronii biovar sobria vacuolating cytotoxic factor. AB - Recently, a cytotoxin named vacuolating cytotoxic factor (VCF) in Aeromonas sobria and Aeromonas veronii biovar sobria was described. We have now purified this factor using ion metallic affinity chromatography. The VCF is a nonhemolytic enterotoxin that acts as a serine protease. The toxin can be partially neutralized by serum antiaerolysin and it induced not only cytoplasmatic vacuole formation, but also mitochondrial disorders that must be signaling the apoptotic pathways, leading to Vero (African green monkey kidney) cell death. These results suggest that the VCF is a virulence factor of these bacteria, participating in the processes of human disease provoked by preformed toxins in food and infection. PMID- 17286563 TI - Gender differences in Brugada syndrome. PMID- 17286564 TI - An a "MAZE"ing arrhythmia. PMID- 17286565 TI - Atrial arrhythmia after a first atrial fibrillation ablation: what is the mechanism? PMID- 17286566 TI - Monophasic action potential recordings in humans. AB - Bridging basic and clinical electrophysiology has been facilitated by monophasic action potential recordings. The electrocardiogram is a useful clinical approach in detecting abnormal repolarization, but falls short in depicting local repolarization details. The MAP waveform is a reflection of local transmembrane action potentials. We hope to convey a basic understanding of monophasic action potential recording and highlight the clinical utility in both ventricular and atrial arrhythmias. PMID- 17286567 TI - Left atrial appendage exclusion and the risk of thromboembolic events following mitral valve surgery. AB - OBJECTIVES: We aimed to evaluate left atrial appendage (LAA) exclusion in patients undergoing mitral valve surgery with respect to thromboembolic events. BACKGROUND: LAA is the predominant source of emboli in patients with atrial fibrillation. Prophylactic LAA exclusion at the time of heart surgery has been recommended to reduce the risk of future thromboembolism. METHODS: An observational cohort of 136 patients undergoing LAA exclusion during mitral valve surgery was identified between May 1993 and November 1998 at our institution. RESULTS: During a mean follow-up of 3.6 +/- 1.3 years, there were 14 (12.3%) thromboembolic events. Compared with patients who received warfarin upon hospital discharge, there were more thromboembolic events in patients not prescribed warfarin upon hospital discharge (n = 7/67, 10% vs n = 6/40, 15%, respectively). The warfarin status was not known for one patient. The majority of thromboembolic events (n = 10/14, 71%) occurred in those who underwent mitral valve repair. CONCLUSION: In this observational study, patients who undergo LAA exclusion during mitral valve surgery to reduce the risk of thromboembolism have a significant incidence of thromboembolic events, especially when warfarin therapy is not prescribed upon hospital discharge. PMID- 17286568 TI - Focal atrial tachycardias arising from the right atrial appendage: electrocardiographic and electrophysiologic characteristics and radiofrequency ablation. AB - OBJECTIVE: To characterize the electrocardiographic and electrophysiological features and frequency of focal atrial tachycardia (AT) originating from the right atrial appendage (RAA). BACKGROUND: The RAA has been described as a site of origin of AT, but detailed characterization of these tachycardias is limited. METHODS: Ten patients (3.8%) of 261 undergoing radiofrequency ablation (RFA) for focal AT are reported. Endocardial activation maps (EAM) were recorded from catheters at the CS (10 pole), tricuspid annulus (20 pole Halo catheter), and His positions. P waves were classified as negative, positive, isoelectric, or biphasic. RESULTS: The mean age was 39 +/- 20 years, nine males, with symptoms for 4.1 +/- 5.1 years. Tachycardia was incessant in seven patients, spontaneous in one patient, and induced by programmed extrastimuli in two patients. These foci had a characteristic P wave morphology. The P wave was negative in lead V(1) in all patients, becoming progressively positive across the precordial leads. The P waves in the inferior leads were low amplitude positive in the majority of patients. Earliest EAM activity occurred on the Halo catheter in all patients. Mean activation time at the successful RFA site =-38 +/- 15 msec. Irrigated catheters were used in six patients, due to difficulty achieving adequate power. RFA was acutely successful in all patients. Long-term success was achieved in all patients over a mean follow up of 8 +/- 7 months. CONCLUSIONS: The RAA is an uncommon site of origin for focal AT (3.8%). It can be suspected as a potential anatomic site of AT origin from the characteristic P wave and activation timing. Irrigated ablation catheters are often required for successful ablation. Long term success was achieved with focal ablation in all patients. PMID- 17286570 TI - Ibutilide-induced cardioversion of atrial fibrillation during pregnancy. AB - We present two cases of successful cardioversion of atrial fibrillation using intravenous ibutilide during pregnancy. One patient had atrial fibrillation, complicating the Wolff-Parkinson-White syndrome and the other had a history of nonobstructive hypertrophic cardiomyopathy. No adverse maternal or fetal effects were observed during or after pregnancy in either case. PMID- 17286569 TI - Clinical implications of reconnection between the left atrium and isolated pulmonary veins provoked by adenosine triphosphate after extensive encircling pulmonary vein isolation. AB - INTRODUCTION: Dormant pulmonary vein (PV) conduction can be provoked by adenosine triphosphate (ATP) after extensive encircling pulmonary vein isolation (EEPVI). However, the clinical implication of reconnection between the left atrium (LA) and isolated PVs provoked by ATP (ATP-reconnection) remains unknown. METHODS AND RESULTS: We studied the clinical consequences of ATP-reconnection during intravenous isoproterenol infusion (ISP-infusion). EEPVI severs conduction between the LA and ipsilateral PVs at their junction. Radiofrequency energy is applied at a distance from the PV ostia guided by double Lasso catheters placed within the ipsilateral superior and inferior PVs. This study comprised 82 patients (67 men, 56 +/- 9 years old) with atrial fibrillation (AF) who underwent injection of ATP during ISP infusion after successful EEPVI (ATP(+) group). We compared clinical characteristics of 170 patients who underwent earlier EEPVI prior to our use of ATP injection after successful EEPVI (ATP(N/D) group) with those of ATP(+) group patients who underwent one session of EEPVI. ATP reconnection occurred in 34 (41%) of 82 ATP(+) group patients. Additional radiofrequency applications were performed to eliminate ATP-reconnection in all ipsilateral PVs. Continuous ATP-reconnection of more than 20 seconds duration occurred in six (7.3%) of 82 patients. A total of 102 (60%) of 170 patients in the ATP(N/D) group had no recurrence of AF, whereas 60 (73%) of 82 ATP(+) group patients who underwent only one EEPVI session have had no recurrence of AF in a 6.1 +/- 3.3-month follow-up period (P = 0.04). CONCLUSION: Radiofrequency application for provoked ATP-reconnection may reduce clinical AF recurrence. PMID- 17286571 TI - Isolation and characterization of an amiloride-resistant mutant of Methanothermobacter thermautotrophicus possessing a defective Na+/H+ antiport. AB - A spontaneous mutant of Methanothermobacter thermautotrophicus resistant to the Na+/H+ antiporter inhibitor amiloride was isolated. The Na+/H+ exchanger activity in the mutant cells was remarkably decreased in comparison with wild-type cells. Methanogenesis rates in the mutant strain were higher than wild-type cells and resistant to the inhibitory effect of 2 mM amiloride. In contrast, methanogenesis in wild-type cells was completely inhibited by the same amiloride concentration. ATP synthesis driven by methanogenic electron transport or by an electrogenic potassium efflux in the presence of sodium ions was significantly enhanced in the mutant cells. ATP synthesis driven by potassium diffusion potential was profoundly inhibited in wild-type cells by the presence of uncoupler 3,3',4',5- tetrachlorosalicylanilide and sodium ions, whereas c. 50% inhibition was observed in the mutant cells under the same conditions. PMID- 17286573 TI - Protein biogenesis in Archaea: addressing translation initiation using an in vitro protein synthesis system for Haloferax volcanii. AB - Translation initiation in Archaea combines aspects of the parallel process in Eukarya and Bacteria alongside traits unique to this domain. To better understand translation initiation in Archaea, an in vitro translation system from the haloarchaeon Haloferax volcanii has been developed. The ability to translate individual mRNAs both under the conditions used in previously developed poly(U) dependent poly(Phe) synthesis systems as well as under physiological conditions was shown. Using the H. volcanii system, mRNAs proceeded by either 'strong' or 'weak' Shine-Dalgarno (SD) motifs, or completely lacking leader sequences were effectively translated. The in vitro haloarchaeal system also successfully translated mRNA from Bacteria, again either presenting a SD initiation motif or completely lacking a leader sequence. Thus, the ability to translate individual mRNAs in vitro offers a system to address translation initiation as well as other aspects of protein biogenesis in Archaea. PMID- 17286572 TI - Mycosporines and mycosporine-like amino acids: UV protectants or multipurpose secondary metabolites? AB - Mycosporines and mycosporine-like amino acids (MAAs) are low-molecular-weight water-soluble molecules absorbing UV radiation in the wavelength range 310-365 nm. They are accumulated by a wide range of microorganisms, prokaryotic (cyanobacteria) as well as eukaryotic (microalgae, yeasts, and fungi), and a variety of marine macroalgae, corals, and other marine life forms. The role that MAAs play as sunscreen compounds to protect against damage by harmful levels of UV radiation is well established. However, evidence is accumulating that MAAs may have additional functions: they may serve as antioxidant molecules scavenging toxic oxygen radicals, they can be accumulated as compatible solutes following salt stress, their formation is induced by desiccation or by thermal stress in certain organisms, they have been suggested to function as an accessory light harvesting pigment in photosynthesis or as an intracellular nitrogen reservoir, and they are involved in fungal reproduction. Here, the evidence for these additional roles of MAAs as 'multipurpose' secondary metabolites is reviewed, with special emphasis on their functions in the microbial world. PMID- 17286574 TI - The Escherichia coli protein YjjG is a house-cleaning nucleotidase in vivo. AB - House-cleaning enzymes protect cells from the adverse effects of noncanonical metabolic chemical compounds. The Escherichia coli nucleotide phosphatase YjjG (B4374, JW4336) functions as a house-cleaning phosphatase in vivo. YjjG protects the cell against noncanonical pyrimidine derivatives such as 5-fluoro-2' deoxyuridine (5-FdUridine), 5-fluorouridine, 5-fluoroorotic acid (5-FOA), 5 fluorouracil, and 5-aza-2'-deoxycytidine. YjjG prevents the incorporation of potentially mutagenic nucleotides into DNA as shown for 5-bromo-2'-deoxyuridine (BrdU). Its enzymatic activity in vitro towards noncanonical 5-fluoro-2' deoxyuridine monophosphate (5-FdUMP) is higher than towards canonical thymidine monophosphate (dTMP). The closest homolog in humans, HDHD4, does not show a protective effect against noncanonical nucleotides, excluding an involvement of HDHD4 in resistance against noncanonical nucleotides used for cancer chemotherapy. The substrate spectrum of YjjG suggests that its in vivo substrates are noncanonical pyrimidine derivatives, which might also include oxidized nucleobases such as 5-formyluracil and 5-hydroxyuracil. PMID- 17286575 TI - Evidence for association of polymorphisms in CYP2J2 and susceptibility to essential hypertension. AB - OBJECTIVE: Evidence from animal models and human studies suggests that CYP2J2 plays a mechanistic role in the development of hypertension. The present study aims to investigate the potential genetic contribution of the CYP2J2 gene to the etiology of essential hypertension (EH) and individual blood pressure. METHODS: We selected eight polymorphisms in/or around the CYP2J2 gene and performed a case control association study involving 841 Han Chinese subjects, including 415 unrelated hypertensives and 426 age-, gender- and area-matched normotensives. RESULTS: Three functionally identified variants (CYP2J2 *2, *7 and CYP2J2 *8) and SNP rs11572182 represented rare polymorphisms in Han Chinese. However, the difference in rs1155002 genotype distribution between hypertensive and healthy subjects was close to significance (P = 0.06) in the whole sample. Interestingly, significant evidence for an association with rs1155002 was found in females when stratified by gender. In females, the TT homozygote of rs1155002 seems to be a risk factor for hypertension (p = 0.014). In addition, ANOVA analysis suggested TT carriers had significantly higher systolic blood pressure (p = 0.016). The genotype frequencies for rs10493270, rs1180273 and rs1324491 revealed no statistically significant differences. Likewise, four-marker haplotype frequencies showed no significant differences between cases and controls. CONCLUSION: Our data provide strong evidence that the CYP2J2 gene is a susceptibility factor for essential hypertension, especially in females, and influences individual systolic blood pressure in the Chinese Han population. PMID- 17286576 TI - Molecular basis for the subunit assembly of the primase from an archaeon Pyrococcus horikoshii. AB - Archaeal/eukaryotic primases form a heterodimer consisting of a small catalytic subunit (PriS) and a large subunit (PriL). The heterodimer complex synthesizes primer oligoribonucleotides that are required for chromosomal replication. Here, we describe crystallographic and biochemical studies of the N-terminal domain (NTD) of PriL (PriL(NTD); residues 1-222) that bind to PriS from a hyperthermophilic archaeon, Pyrococcus horikoshii, at 2.9 A resolution. The PriL(NTD) structure consists of two subdomains, the helix-bundle and twisted strand domains. The latter is structurally flexible, and is expected to contain a PriS interaction site. Pull-down and surface plasmon resonance analyses of structure-based deletion and alanine scanning mutants showed that the conserved hydrophobic Tyr155-Tyr156-Ile157 region near the flexible region is the PriS binding site, as the Y155A/Y156A/I157A mutation markedly reduces PriS binding, by 1000-fold. These findings and a structural comparison with a previously reported PriL(NTD)-PriS complex suggest that the presented alternative conformations of the twisted-strand domain facilitate the heterodimer assembly. PMID- 17286577 TI - Neuroglobin and cytoglobin expression in mice. Evidence for a correlation with reactive oxygen species scavenging. AB - Although essentially unknown, several functions are hypothesized for neuroglobin and cytoglobin, two new members of the globin family. In this article, we try to shed more light on their possible roles in hypoxia and detoxification of reactive oxygen species in vivo. The relative transcriptional changes of neuroglobin and cytoglobin in a situation of chronic hypoxia in mice were examined using real time quantitative PCR. The kinetics of the hypoxic expression of neuroglobin (brain, eyes) and cytoglobin (brain, eyes, liver, heart, skeletal muscle) is organ-specific. Moreover, reactive oxygen species production is higher in liver than in the other tissues. In eyes, the negative correlation, after reoxygenation, between neuroglobin protein level and H(2)O(2) concentration is a first proof of a reactive oxygen species-scavenging function for neuroglobin. In addition, apoptotic cell death after hypoxia is for the first time demonstrated in heart and liver. PMID- 17286578 TI - Phosphorylation of the large subunit of replication factor C is associated with adipocyte differentiation. AB - Adipocyte differentiation is an ordered multistep process requiring the sequential activation of several groups of adipogenic transcription factors, including CCAAT/enhancer-binding protein-alpha and peroxisome proliferator activated receptor-gamma, and coactivators. Here we show that replication factor C 140, which was known to act as a coactivator for CCAAT/enhancer-binding protein alpha in our previous study, was phosphorylated on the proliferating cell nuclear antigen-bindng domain during the adipocyte differentiation process. Calmodulin dependent protein kinase II was responsible for phosphorylating replication factor C 140 in the process of adipocyte differentiation. Ser518 of replication factor C 140 was identified as a major target of calmodulin-dependent protein kinase II phosphorylation in vitro. Calmodulin-dependent protein kinase II inhibitor attenuated phosphorylation of replication factor C 140 by differentiation inducers and blocked replication factor C 140-derived transcriptional activation. Taken together, these findings demonstrate that calmodulin-dependent protein kinase II signaling leads the cooperative transactivation of CCAAT/enhancer-binding protein-alpha and replication factor C 140 through an increase in replication factor C 140 phosphorylation, and subsequently enhances the transcriptional activation of target genes involved in adipocyte differentiation. PMID- 17286579 TI - Direct detection of stereospecific soman hydrolysis by wild-type human serum paraoxonase. AB - Human serum paraoxonase 1 (HuPON1; EC 3.1.8.1) is a calcium-dependent six-fold beta-propeller enzyme that has been shown to hydrolyze an array of substrates, including organophosphorus (OP) chemical warfare nerve agents. Although recent efforts utilizing site-directed mutagenesis have demonstrated specific residues (such as Phe222 and His115) to be important in determining the specificity of OP substrate binding and hydrolysis, little effort has focused on the substrate stereospecificity of the enzyme; different stereoisomers of OPs can differ in their toxicity by several orders of magnitude. For example, the C+/-P- isomers of the chemical warfare agent soman (GD) are known to be more toxic by three orders of magnitude. In this study, the catalytic activity of HuPON1 towards each of the four chiral isomers of GD was measured simultaneously via chiral GC/MS. The catalytic efficiency (k(cat)/K(m)) of the wild-type enzyme for the various stereoisomers was determined by a simultaneous solution of hydrolysis kinetics for each isomer. Derived k(cat)/K(m) values ranged from 625 to 4130 mm(-1).min( 1), with isomers being hydrolyzed in the order of preference C+P+ > C-P+ > C+P- > C-P-. The results indicate that HuPON1 hydrolysis of GD is stereoselective; substrate stereospecificity should be considered in future efforts to enhance the OPase activity of this and other candidate bioscavenger enzymes. PMID- 17286581 TI - Molecular phylogenetic diversity of the microbial community associated with a high-temperature petroleum reservoir at an offshore oilfield. AB - The microbial community and its diversity in production water from a high temperature, water-flooded petroleum reservoir of an offshore oilfield in China were characterized by 16S rRNA gene sequence analysis. The bacterial and archaeal 16S rRNA gene clone libraries were constructed from the community DNA and, using sequence analysis, 388 bacterial and 220 archaeal randomly selected clones were clustered with 60 and 28 phylotypes, respectively. The results showed that the 16S rRNA genes of bacterial clones belonged to the divisions Firmicutes, Thermotogae, Nitrospirae and Proteobacteria, whereas the archaeal library was dominated by methanogen-like rRNA genes (Methanothermobacter, Methanobacter, Methanobrevibacter and Methanococcus), with a lower percentage of clones belonging to Thermoprotei. Thermophilic microorganisms were found in the production water, as well as mesophilic microorganisms such as Pseudomonas and Acinetobacter-like clones. The thermophilic microorganisms may be common inhabitants of geothermally heated specialized subsurface environments, which have been isolated previously from a number of high-temperature petroleum reservoirs worldwide. The mesophilic microorganisms were probably introduced into the reservoir as it was being exploited. The results of this work provide further insight into the composition of microbial communities of high-temperature petroleum reservoirs at offshore oilfields. PMID- 17286583 TI - Glutamate-induced activation of nitric oxide synthase is impaired in cerebral cortex in vivo in rats with chronic liver failure. AB - It has been proposed that impairment of the glutamate-nitric oxide-cyclic guanosine monophosphate (cGMP) pathway in brain contributes to cognitive impairment in hepatic encephalopathy. The aims of this work were to assess whether the function of this pathway and of nitric oxide synthase (NOS) are altered in cerebral cortex in vivo in rats with chronic liver failure due to portacaval shunt (PCS) and whether these alterations are due to hyperammonemia. The glutamate-nitric oxide-cGMP pathway function and NOS activation by NMDA was analysed by in vivo microdialysis in cerebral cortex of PCS and control rats and in rats with hyperammonemia without liver failure. Similar studies were done in cortical slices from these rats and in cultured cortical neurons exposed to ammonia. Basal NOS activity, nitrites and cGMP are increased in cortex of rats with hyperammonemia or liver failure. These increases seem due to increased inducible nitric oxide synthase expression. NOS activation by NMDA is impaired in cerebral cortex in both animal models and in neurons exposed to ammonia. Chronic liver failure increases basal NOS activity, nitric oxide and cGMP but reduces activation of NOS induced by NMDA receptors activation. Hyperammonemia is responsible for both effects which will lead, independently, to alterations contributing to neurological alterations in hepatic encephalopathy. PMID- 17286584 TI - The beta-amyloid protein of Alzheimer's disease binds to membrane lipids but does not bind to the alpha7 nicotinic acetylcholine receptor. AB - Accumulation of the amyloid protein (Abeta) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism by which Abeta exerts its neurotoxic effect is largely unknown. It has been suggested that the peptide can bind to the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). In this study, we examined the binding of Abeta1-42 to endogenous and recombinantly expressed alpha7nAChRs. Abeta1-42 did neither inhibit the specific binding of alpha7nAChR ligands to rat brain homogenate or slice preparations, nor did it influence the activity of alpha7nAChRs expressed in Xenopus oocytes. Similarly, Abeta1-42 did not compete for alpha-bungarotoxin-binding sites on SH-SY5Y cells stably expressing alpha7nAChRs. The effect of the Abeta1-42 on tau phosphorylation was also examined. Although Abeta1-42 altered tau phosphorylation in alpha7nAChR-transfected SH-SY5Y cells, the effect of the peptide was unrelated to alpha7nAChR expression or activity. Binding studies using surface plasmon resonance indicated that the majority of the Abeta bound to membrane lipid, rather than to a protein component. Fluorescence anisotropy experiments indicated that Abeta may disrupt membrane lipid structure or fluidity. We conclude that the effects of Abeta are unlikely to be mediated by direct binding to the alpha7nAChR. Instead, we speculate that Abeta may exert its effects by altering the packing of lipids within the plasma membrane, which could, in turn, influence the function of a variety of receptors and channels on the cell surface. PMID- 17286585 TI - The 20S proteasome isolated from Alzheimer's disease brain shows post translational modifications but unchanged proteolytic activity. AB - Chronic neurodegenerative diseases are characterized by the accumulation of aggregated protein species, and functional impairment of the ubiquitin proteasome system has been hypothesized to contribute to neuronal cell loss. Decreased proteolytic activity of the 20S proteasome has been shown postmortem in crude brain lysates from Alzheimer's disease (AD) patients. In the present study, we demonstrate, however, that catalytic activity of the 20S proteasome increases during chromatographic purification from AD brains as compared with age-matched controls. By two-dimensional difference gel electrophoresis we detected pI shifts in several proteasome subunits in AD samples pointing to differential post translational modifications. Moreover, we identified N-terminal acetylation and dephosphorylation of subunit alpha7 in AD by tandem mass spectrometry. Thus, reduced peptidase activity in AD brain extracts is not an intrinsic property of the 20S proteasome, but may be resulting from the presence of endogenous inhibitory proteins or substrates. Post-translational modifications of non catalytic subunits in situ may contribute to the trend towards enhanced hydrolytic activity of the isolated 20S proteasome after removal of the endogenous inhibitors. PMID- 17286586 TI - Formation of glycerol from glucose in rat brain and cultured brain cells. Augmentation with kainate or ischemia. AB - An increase in the concentration of glycerol in the ischemic brain is assumed to reflect degradation of phospholipids of plasma membranes. However, glycerol could, theoretically, be formed from glucose, which after glycolytic conversion to dihydroxyacetone phosphate, could be converted to glycerol-3-phosphate and hence to glycerol. We show here that (13)C-labeled glycerol accumulate in incubation media of cultured cerebellar granule cells and astrocytes incubated with [(13)C]glucose, 3 mmol/L, demonstrating the formation of glycerol from glucose. Co-incubation of cerebellar granule cells with kainate, 50 micromol/L, led to increased glucose metabolism and increased accumulation of [(13)C]glycerol. Accumulation of [(13)C]glycerol and its precursor, [(13)C]glycerol-3-phosphate, was evident in brain, but not in serum, of kainate treated rats that received [U-(13)C]glucose, 5 micromol/g bodyweight, intravenously and survived for 5 min. Global ischemia induced by decapitation also caused accumulation of [(13)C]glycerol and [(13)C]glycerol-3-phosphate. These results show that glycerol can be formed from glucose in brain; they also demonstrate the existence of a cerebral glycerol-3-phosphatase activity. Ischemia induced increases in brain glycerol may, in part, reflect an altered metabolism of glucose, in which glycerol formation, like lactate formation, acts as a redox sink. PMID- 17286587 TI - Melanocortin receptor 4 is induced in nerve-injured motor and sensory neurons of mouse. AB - We previously identified melanocortin receptor 4 (MC4R) in a search for genes associated with hypoglossal nerve regeneration. As melanocortins promote nerve regeneration after axonal injury, we investigated whether MC4R functions as a key receptor for peripheral nerve regeneration. In situ hybridization revealed that MC4R mRNA is induced in mouse hypoglossal motor neurons after axonal injury, whereas mRNAs for MC1R, MC2R, MC3R, and MC5R are not expressed either before or after nerve injury. This result was confirmed by RT-PCR. The level of MC4R mRNA expression increased significantly from day 3 after axotomy, reached a peak on day 5, and decreased to the control level on day 14. Similar induction of MC4R was observed in axotomized mouse dorsal root ganglia (DRGs). MC4R mRNA expression was induced exclusively among the MCR family in the L4-6 DRG after sciatic nerve injury. We further examined whether alpha-melanocortin stimulating hormone (alpha MSH) promotes neurite elongation via MC4R. In mouse DRG neuron culture, alpha-MSH significantly promoted neurite outgrowth at a concentration of 10(-8) mol/L. This neurite-elongation effect was entirely inhibited by the addition of a selective MC4R blocker, JKC-363. Therefore, it is concluded that alpha-MSH could stimulate neurite elongation via MC4R in DRG neurons. The present results suggest that induction of MC4R is crucial for motor and sensory neurons to regenerate after axonal injury. PMID- 17286588 TI - Dopaminergic neurons intrinsic to the striatum. AB - The striatum -- the largest integrative component of the basal ganglia -- harbors a population of neurons that express the enzyme tyrosine hydroxylase (TH), a faithful marker of dopaminergic neurons. The dopaminergic nature of these neurons is further supported by the fact that they express the dopamine (DA) transporter (DAT) and the nuclear orphan receptor Nurr1, a transcription factor essential for the expression of the DA phenotype by midbrain neurons. The vast majority of these neurons are morphologically similar to the medium-sized aspiny striatal interneurons and they all express the enzyme GAD(65). The striatal TH-positive neurons increase markedly in number in animal models of Parkinson's disease (PD), where striatal DA concentrations are low, but this increase is abolished by L dopa treatment. Hence, local DA concentrations appear to regulate the numerical density of this ectopic neuronal population, a phenomenon that is more likely the result of a shift in the phenotype of preexistent striatal interneurons rather than the recruitment of newborn neurons that will develop a DA phenotype. Altogether, these findings suggest that striatal TH-positive neurons act as a local source of DA and, as such, are part of a compensatory mechanism that could be artificially enhanced to alleviate or delay PD symptoms. PMID- 17286589 TI - Mechanisms involved in the formation of dopamine-induced intracellular bodies within striatal neurons. AB - Recent studies demonstrated that methamphetamine (METH) produces intracellular bodies which are reminiscent of those occurring during degenerative disorders. In vivo studies demonstrate the occurrence of these morphological alterations both in the dopamine (DA) neurons of the substantia nigra and striatal cells. These consist of neuronal bodies staining for a variety of antigens belonging to the ubiquitin-proteasome pathway. The formation of these intracellular bodies both in the substantia nigra and PC12 cells depends on the presence of endogenous DA. In the present study, we analyze the mechanisms which lead to METH-induced intracellular bodies within non-dopaminergic striatal neurons. We found that METH is no longer able to produce inclusions in vivo, in striatal cells, when striatal DA is lost. Similarly, in vitro, in primary striatal cell cultures which do not possess DA, METH administration does not produce inclusions. On the other hand, administration of DA to striatal cell cultures produces neuronal inclusions and cell death, which are both related to the inhibition of the ubiquitin-proteasome system and activation of specific-DA receptors. In line with this, we produced subcellular alterations by administering dopamine agonists. PMID- 17286590 TI - A beta oligomers - a decade of discovery. AB - Converging lines of evidence suggest that progressive accumulation of the amyloid beta-protein (A beta) plays a central role in the genesis of Alzheimer's disease, but it was long assumed that A beta had to be assembled into extracellular amyloid fibrils to exert its cytotoxic effects. Over the past decade, data have emerged from the use of synthetic A beta peptides, cell culture models, beta amyloid precursor protein transgenic mice and human brain to suggest that pre fibrillar, diffusible assemblies of A beta are also deleterious. Although the precise molecular identity of these soluble toxins remains unsettled, accumulating evidence suggests that soluble forms of A beta are indeed the proximate effectors of synapse loss and neuronal injury. Here we review recent progress in understanding the role of soluble oligomers in Alzheimer's disease. PMID- 17286591 TI - Possible involvement of protease-activated receptor-1 in the regulation of morphine-induced dopamine release and hyperlocomotion by the tissue plasminogen activator-plasmin system. AB - We have previously demonstrated that tissue plasminogen activator (tPA)-plasmin system participates in the rewarding effect of morphine, by regulating dopamine release in the nucleus accumbens (NAc). However, it is unclear how plasmin increases the morphine-induced release of dopamine and hyperlocomotion. In the present study we investigated whether protease activated receptor-1 (PAR-1) is involved in the regulation of acute morphine-induced dopamine release by the tPA plasmin system. Morphine significantly but transiently increased extracellular tPA activity in the NAc, which was completely blocked by naloxone. Microinjection of a PAR-1 antagonist, (tyr(-1))-thrombin receptor activating peptide 7, into the NAc significantly reduced morphine-induced dopamine release in the NAc and hyperlocomotion although the treatment had no effect on basal dopamine release and spontaneous locomotor activity. Furthermore, the PAR-1 antagonist blocked the ameliorating effect of plasmin on the defect of morphine-induced dopamine release in the NAc of tPA-deficient mice. In contrast, intracerebroventricular injection of the PAR-1 antagonist had no effect on the antinociceptive effects of morphine in mice. These results suggest that PAR-1 is a target for the tPA-plasmin system in the regulation of acute morphine-induced dopamine release in the NAc. PMID- 17286592 TI - CB1 receptors diminish both Ca(2+) influx and glutamate release through two different mechanisms active in distinct populations of cerebrocortical nerve terminals. AB - We have investigated the mechanisms by which activation of cannabinoid receptors reduces glutamate release from cerebrocortical nerve terminals. Glutamate release evoked by depolarization of nerve terminals with high KCl (30 mmol/L) involves N and P/Q type Ca(2+)channel activation. However, this release of glutamate is independent of Na(+) or K(+) channel activation as it was unaffected by blockers of these channels (tetrodotoxin -TTX- or tetraethylammonium TEA). Under these conditions in which only Ca(2+) channels contribute to pre-synaptic activity, the activation of cannabinoid receptors with WIN55,212-2 moderately reduced glutamate release (26.4 +/- 1.2%) by a mechanism that in this in vitro model is resistant to TTX and consistent with the inhibition of Ca(2+) channels. However, when nerve terminals are stimulated with low KCl concentrations (5-10 mmol/L) glutamate release is affected by both Ca(2+) antagonists and also by TTX and TEA, indicating the participation of Na(+) and K(+) channel firing in addition to Ca(2+) channel activation. Interestingly, stimulation of nerve terminals with low KCl concentrations uncovered a mechanism that further inhibited glutamate release (81.78 +/- 4.9%) and that was fully reversed by TEA. This additional mechanism is TTX-sensitive and consistent with the activation of K(+) channels. Furthermore, Ca(2+) imaging of single boutons demonstrated that the two pre-synaptic mechanisms by which cannabinoid receptors reduce glutamate release operate in distinct populations of nerve terminals. PMID- 17286593 TI - Activation of stress-related hypothalamic neuropeptide gene expression during morphine withdrawal. AB - Morphine withdrawal results in serious affective and somatic symptoms including activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. To reveal secretory, activational and transcriptional changes in the hypothalamus of morphine-dependent rats during naloxone precipitated opioid withdrawal, we measured corticosterone secretion, c-Fos induction and heteronuclear (hn)RNA levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in naive and morphine dependent animals injected with saline or 5 mg/kg naloxone. Naloxone precipitated morphine withdrawal resulted in a significant increase in corticosterone secretion and induction of neuronal activation in the hypothalamic paraventricular nucleus (PVH) 2 h after challenge. Using probes complementary to intronic sequences of genes encoding neuropeptides in parvocellular neurosecretory neurons of the PVH, we found robust increases in CRH and AVP hnRNAs in morphine dependent rats during naloxone precipitated withdrawal. Naive rats and animals that were implanted with morphine pellets for 8 days did not display significant up-regulation of ongoing neuropeptide expression in the parvocellular compartment of the PVH. In addition to hypophyseotropic neurons, naloxone precipitated withdrawal resulted in a marked activation in autonomic related projection neurons in PVH and in the magnocellular neurons in the PVH and supraoptic nuclei. These activations however were not associated with induction of CRH or AVP hnRNAs. PMID- 17286594 TI - Serotonin and neuronal growth factors - a convergence of signaling pathways. AB - Monoamines, including serotonin (5-HT), have traditionally been associated with short-term signaling pathways in neurons, such as the modulation of cAMP and Ca(2+) levels. In contrast, neuronal growth factors, such as neurotrophins, have been traditionally associated with signaling pathways, such as those for activation of extracellular-regulated kinase (ERK) and Akt (protein kinase B), which are known to induce long-term protective changes. It has therefore been unclear how antidepressants that increase serotonin (5-HT), induce such changes as hippocampal neuroprotection and neurogenesis. It has been hypothesized, that the actions of 5-HT may be mediated indirectly through increased synthesis of peptide growth factors. However, there is increasing evidence that some subtypes of 5-HT receptors can directly couple to activation of the ERK and Akt pathways. Such coupling suggests a more direct potential role for 5-HT in mediating the long-term actions induced by antidepressants. PMID- 17286595 TI - Propionate increases neuronal histone acetylation, but is metabolized oxidatively by glia. Relevance for propionic acidemia. AB - In propionic acidemia, propionate acts as a metabolic toxin in liver cells by accumulating in mitochondria as propionyl-CoA and its derivative, methylcitrate, two tricarboxylic acid cycle inhibitors. Little is known about the cerebral metabolism of propionate, although clinical effects of propionic acidemia are largely neurological. We found that propionate was metabolized oxidatively by glia: [3-(14)C]propionate injected into mouse striatum or cortex, gave a specific activity of glutamine that was 5-6 times that of glutamate, indicating metabolism in cells that express glutamine synthetase, i.e., glia. Further, cultured cerebellar astrocytes metabolized [3-(14)C]propionate; cultured neurons did not. However, both cultured cerebellar neurons and astrocytes took up [3H]propionate, and propionate exposure increased histone acetylation in cultured neurons and astrocytes as well as in hippocampal CA3 pyramidal neurons of wake mice. The inability of neurons to metabolize propionate may be due to lack of mitochondrial propionyl-CoA synthetase activity or transport of propionyl residues into mitochondria, as cultured neurons expressed propionyl-CoA carboxylase, a mitochondrial matrix enzyme, and oxidized isoleucine, which becomes converted into propionyl-CoA intramitochondrially. The glial metabolism of propionate suggests astrocytic vulnerability in propionic acidemia when intramitochondrial propionyl-CoA may accumulate. Propionic acidemia may alter both neuronal and glial gene expression by affecting histone acetylation. PMID- 17286596 TI - Follicular epithelia and dermal papillae of mouse vibrissal follicles qualitatively change their hair-forming ability during anagen. AB - We studied the hair-forming ability of epithelium and the relevant activity of dermal papilla (DP) in mouse vibrissal follicles during the hair cycle. Follicles were transversely cut into four pieces and each of them was associated with an isolated DP and grafted beneath the kidney capsule to induce hair formation. Various hair-cycle combinations of the fragments and DPs were examined. Hairs were generated not only in the follicle fragment containing the bulge (fragment III) but also in the fragment between the bulge and hair bulb (fragment II). The hair-forming frequencies were affected by the hair cycle stages of both the follicle fragments and DPs. Fragment III at late anagen (LA) and fragment II at catagen frequently generated hairs when associated with early anagen (EA)-DPs, but infrequently with mid-anagen (MA)-DPs. Oppositely, anagen fragment II produced hairs at a high frequency with MA-DPs and at a low frequency with EA DPs. Hair generation in anagen fragment II is an unexpected finding because previous studies suggested that, during anagen, this region does not contain clonogenic epithelial cells that have been believed to be crucial for hair formation. Therefore, non-clonogenic epithelial cells would be able to generate hairs as well as clonogenic ones, and they should have a latent hair-forming ability that could be more effectively awakened by MA-DP than by EA-DP stimuli. Non-clonogenic epithelial cells might be a dormant phase of hair precursor cells. Proliferating follicular epithelial cells were detected in the middle and lower outer root sheath throughout the hair cycle but scarcely at LA. These findings suggest that the hair inductivity of DPs should be altered between EA and MA, and follicular epithelial cells would change their DP stimuli-directed hair-forming ability around LA, probably linked to the proliferative activity. PMID- 17286597 TI - Differentiation of liver cells from human primordial germ cell-derived progenitors. AB - In previous studies, progenitor embryoid body-derived (EBD) cells have been derived from human embryonic germ cells. These cells express lineage markers of three primary germ layers, although their potential to produce true fetal cells of various types has yet to be tested. To this end, we have transplanted EBD cells into the fetal sheep liver. We show that these cells respond appropriately to environmental cues and give rise to hepatocytes and well-structured bile ducts. These results suggest that EBD cells are relatively uncommitted early progenitors capable of effective incorporation and differentiation in vivo. The ability to generate functional liver cells makes EBD cells potentially useful for cell therapy. PMID- 17286598 TI - Wnt10a regulates dentin sialophosphoprotein mRNA expression and possibly links odontoblast differentiation and tooth morphogenesis. AB - We have explored the role of Wnt signaling in dentinogenesis of mouse molar teeth. We found that Wnt10a was specifically associated with the differentiation of odontoblasts and that it showed striking colocalization with dentin sialophosphoprotein (Dspp) expression in secretory odontoblasts. Dspp is a tooth specific non-collagenous matrix protein and regulates dentin mineralization. Transient overexpression of Wnt10 in C3H10T1/2, a pluripotent fibroblast cell line induced Dspp mRNA. Interestingly, this induction occurred only when transfected cells were cultured on Matrigel basement membrane extracts. These findings indicated that Wnt10a is an upstream regulatory molecule for Dspp expression, and that cell-matrix interaction is essential for induction of Dspp expression. Furthermore, Wnt10a was specifically expressed in the epithelial signaling centers regulating tooth development, the primary and secondary enamel knots. The spatial and temporal distribution of Wnt10a mRNA demonstrated that the expression shifts from the secondary enamel knots, to the underlying preodontoblasts in the tips of future cusps. The expression patterns and overexpression studies together indicate that Wnt10a is a key molecule for dentinogenesis and that it is associated with the cell-matrix interactions regulating odontoblast differentiation. We conclude that Wnt10a may link the differentiation of odontoblasts and cusp morphogenesis. PMID- 17286599 TI - In vitro differentiation of murine embryonic stem cells toward a renal lineage. AB - Embryonic stem (ES) cells have the capacity to differentiate into all cells of the developing embryo and may provide a renewable resource for future cell replacement therapies. The addition of bone morphogenetic protein 4 (BMP4) to serum-free ES cell culture has previously been shown to induce transcription factors, signaling molecules, and cell adhesion proteins expressed during mesoderm specification of the embryo. Here, we show the dynamics of primitive streak mesoderm differentiation in ES cells is comparable between serum and serum free embryoid body (EB) cultures, supplemented with BMP4. Furthermore, we show a delayed wave of expression of a cohort of genes (Pax2, WT1, podocalyxin, pod-1, and nephrin), which play important roles during embryonic kidney development. The paired box transcription factor, Pax2, is one of the earliest genes expressed during kidney organogenesis and is required for normal urogenital development. ES cell lines containing either a modified Pax2 promoter-lacZ or bacterial artificial chromosome-green fluorescent protein (GFP) transgene were generated, which enabled the quantitative analysis of kidney rather than neuronal Pax2 expression within EBs. Both beta-galactosidase activity and GFP expression were detected by immunohistochemical and flow cytometric analysis following 16 days of EB culture, which correlated with an increase in Pax2 transcript levels. Together, these results suggest a spontaneous kidney gene expression program develops in mature EBs grown in both serum and serum-free conditions, when supplemented with BMP4. Further, the recombinant growth factors BMP2, BMP4, and BMP7 strongly influence gene expression within mesoderm induced EBs. BMP4 promotes ventral (blood) and intermediate (kidney) mesoderm gene expression, whereas BMP2 and BMP7 promote kidney outcomes at the expense of hematopoietic commitment. This induction assay and these unique ES cell lines will be useful for the generation of mesoderm-derived cell populations with implications for future cell therapeutic/integration assays. PMID- 17286600 TI - Drosophila Anaplastic Lymphoma Kinase regulates Dpp signalling in the developing embryonic gut. AB - The Drosophila melanogaster gene Anaplastic Lymphoma Kinase (Alk) regulates a signal transduction pathway required for founder cell specification within the visceral muscle of the developing embryonic midgut. During embryonic development, the midgut visceral muscle is lined by the endodermal cell layer. In this paper, we have investigated signalling between these two tissues. Here, we show that Alk function is required for decapentaplegic (Dpp) expression and subsequent signalling via the Mad pathway in the developing gut. We propose that not only does Alk signalling regulate founder cell specification and thus fusion in the developing visceral muscle, but that Alk also regulates Dpp signalling between the visceral muscle and the endoderm. This provides an elegant mechanism with which to temporally coordinate visceral muscle fusion and later events in midgut development. PMID- 17286601 TI - Early molecular effects of ethanol during vertebrate embryogenesis. AB - Fetal alcohol spectrum disorder (FASD) is the combination of developmental, morphological, and neurological defects that result from exposing human embryos to ethanol (EtOH). Numerous embryonic structures are affected, leading to a complex viable phenotype affecting among others, the anterior/posterior axis, head, and eye formation. Recent studies have provided evidence suggesting that EtOH teratogenesis is mediated in part through a reduction in retinoic acid (RA) levels, targeting mainly the embryonic organizer (Spemann's organizer) and its subsequent functions. EtOH-treated Xenopus embryos were subjected to an analysis of gene expression patterns. Analysis of organizer-specific genes revealed a transient delay in the invagination of gsc- and chordin-positive cells that eventually reach their normal rostro-caudal position. Dorsal midline genes show defects along the rostro-caudal axis, lacking either their rostral (Xbra and Xnot2) or caudal (FoxA4b and Shh) expression domains. Head-specific markers like Otx2, en2, and Shh show abnormal expression patterns. Otx2 exhibits a reduction in expression levels, while en2 becomes restricted along the dorsal/ventral axis. During neurula stages, Shh becomes up-regulated in the rostral region and it is expressed in an abnormal pattern. These results and histological analysis suggest the existence of malformations in the brain region including a lack of the normal fore brain ventricle. An increase in the size of both the prechordal plate and the notochord was observed, while the spinal cord is narrower. The reduction in head and eye size was accompanied by changes in the eye markers, Pax6 and Tbx3. Our results provide evidence for the early molecular changes induced by EtOH exposure during embryogenesis, and may explain some of the structural changes that are part of the EtOH teratogenic phenotype also in FASD individuals. PMID- 17286602 TI - Culture and differentiation of preadipocytes in two-dimensional and three dimensional in vitro systems. AB - Adipogenesis is a complex process that involves the differentiation of preadipocytes into mature adipocytes. We have developed two-dimensional (2D) and three-dimensional (3D) cell culture systems for the purpose of culturing and differentiating primary preadipocytes in vitro. Differentiating preadipocytes show multiple lipid droplet accumulation and comparable protein expression patterns to mature adipocytes in vivo. We report that in both in vitro systems terminally differentiated adipocytes show characteristics similar to those of mature adipocytes in vivo, assessed by the expression of the S100alpha/beta protein, insulin receptor and caveolin-1, and receptors for inflammatory mediators, namely tumor necrosis factor-alpha receptors I and II (TNFRI and TNFRII) and chemokine receptor 5 (CCR5). Our results demonstrate that the S100 protein, caveolin-1, and insulin receptor are expressed and up-regulated in differentiating and terminally differentiated cells. In addition, the receptors for TNFalpha are not present in preadipocytes but are expressed in differentiating preadipocytes and in differentiated adipocytes. Similarly, CCR5 was exclusively expressed in differentiating preadipocytes and terminally differentiated adipocytes, but not in preadipocytes. Both 2D and 3D culture models are highly robust and reproducible and offer the potential to study adipogenesis and cellular interactions closely resembling and comparable to those in vivo. Our 3D collagen system offers a distinct advantage over the 2D system in that the adipocytes remain confined within the matrix and remain intact during biochemical analysis. Moreover, the collagen matrix allows adipocytes to closely simulate morphological characteristics and behavior as in vivo whilst permitting manipulation of the microenvironment in vitro to study adipogenesis. PMID- 17286603 TI - Neural crest and mesoderm lineage-dependent gene expression in orofacial development. AB - The present study utilizes a combination of genetic labeling/selective isolation of pluripotent embryonic progenitor cells, and oligonucleotide-based microarray technology, to delineate and compare the "molecular fingerprint" of two mesenchymal cell populations from distinct lineages in the developing embryonic orofacial region. The first branchial arches-bi-lateral tissue primordia that flank the primitive oral cavity-are populated by pluripotent mesenchymal cells from two different lineages: neural crest (neuroectoderm)- and mesoderm-derived mesenchymal cells. These cells give rise to all of the connective tissue elements (bone, cartilage, smooth and skeletal muscle, dentin) of the orofacial region (maxillary and mandibular portion), as well as neurons and glia associated with the cranial ganglia, among other tissues. In the present study, neural crest- and mesoderm-derived mesenchymal cells were selectively isolated from the first branchial arch of gestational day 9.5 mouse embryos using laser capture microdissection (LCM). The two different embryonic cell lineages were distinguished through utilization of a novel two component transgenic mouse model (Wnt1Cre/ZEG) in which the neural crest cells and their derivatives are indelibly marked (i.e., expressing enhanced green fluorescent protein, EGFP) throughout the pre- and post-natal lifespan of the organism. EGFP-labeled neural crest-derived, and non-fluorescent mesoderm-derived mesenchymal cells from the first branchial arch were visualized in frozen tissue sections from gestational day 9.5 mouse embryos and independently isolated by LCM under epifluorescence optics. RNA was extracted from the two populations of LCM-procured cells, and amplified by double stranded cDNA synthesis and in vitro transcription. Gene expression profiles of the two progenitor cell populations were generated via hybridization of the cell type specific cRNA samples to oligo-based GeneChip microarrays. Comparison of gene expression profiles of neural crest- and mesoderm-derived mesenchymal cells from the first branchial arch revealed over 140 genes that exhibited statistically significant differential levels of expression. The gene products of many of these differentially expressed genes have previously been linked to the development of mesoderm- or neural crest-derived tissues in the embryo. Interestingly, however, hitherto uncharacterized coding sequences with highly significant differences in expression between the two embryonic progenitor cell types were also identified. These lineage-dependent mesenchymal cell molecular fingerprints offer the opportunity to elucidate additional mechanisms governing cellular growth, differentiation, and morphogenesis of the embryonic orofacial region. The chemokine stromal cell-derived factor 1, (SDF-1), was found to exhibit greater expression in mesoderm-derived mesenchyme in the branchial arch when compared with neurectoderm, suggesting a possible chemotactic role for SDF-1 in guiding the migratory neural crest cells to their destination. The novel combination of genetic labeling of the neural crest cell population by EGFP coupled with isolation of cells by LCM for gene expression analysis has enabled, for the first time, the generation of gene expression profiles of distinct embryonic cell lineages. PMID- 17286604 TI - MEK/ERK signaling contributes to the maintenance of human embryonic stem cell self-renewal. AB - MEK/ERK signaling plays a crucial role in a diverse set of cellular functions including cell proliferation, differentiation and survival, and recently has been reported to negatively regulate mouse embryonic stem cell (mESC) self-renewal by antagonizing STAT3 activity. However, its role in human ESCs (hESCs) remains unclear. Here we investigated the functions of MEK/ERK in controlling hESC activity. We demonstrated that MEK/ERK kinases were targets of fibroblast growth factor (FGF) pathway in hESCs. Surprisingly, we found that, in contrast to mESCs, high basal MEK/ERK activity was required for maintaining hESCs in an undifferentiated state. Inhibition of MEK/ERK activity by specific MEK inhibitors PD98059 and U0126, or by RNA interference, rapidly caused the loss of self renewal capacity. We also showed that MEK/ERK signaling cooperated with phosphoinositide 3-kinase (PI3K)/AKT signaling in maintaining hESC pluripotency. However, MEK/ERK signaling had little or no effect on regulating hESC proliferation and survival, in contrast to PI3K/AKT signaling. Taken together, these findings reveal the unique and crucial role of MEK/ERK signaling in the determination of hESC cell fate and expand our understanding of the molecular mechanisms behind the FGF pathway maintenance of hESC pluripotency. Importantly, these data make evident the striking differences in the control of self-renewal between hESCs and mESCs. PMID- 17286606 TI - Influence of surface modification on vitality and differentiation of Caco-2 cells. AB - It is widely accepted that the functional and morphological differentiation of cells is initiated and determined by the interaction of molecules of the extracellular matrix and adhesion molecules of the cell membrane. To assess the influence of the underlying matrix on the characteristics of cells, enterocyte like Caco-2 cells were cultivated on substrates commonly used for cell culture as well as on glass coated with hydrophobic layers. Providing the same starting conditions for growth, the parameters investigated on preconfluent Caco-2 cells were the number of adhering cells, the proliferative activity and the degree of differentiation indicated by the expression of three brush border enzymes. Whereas tissue culture treated polystyrene elicited highest rates of adhesion, proliferation, and differentiation, even glass altered the pattern of brush border enzyme expression. The hydrophobic surfaces strongly decreased the adhesion and the proliferation but the surviving cells exhibited a pronounced higher degree of differentiation. Interestingly, each sub-type of hydrophobic matrix triggered a different pattern of brush border enzyme expression. Thus, the development of a certain phenotype of a cell can not only be triggered by certain components of the extracellular matrix but also by artificially prepared surface coatings of the underlying matrix. In the future it seems to be feasible that cells can be programmed by tailoring the surface of the underlying substrate. PMID- 17286605 TI - Dynamics of expression of growth differentiation factor 15 in normal and PIN development in the mouse. AB - Growth differentiation factor (GDF15) is a distant member of the transforming growth factor-beta superfamily, a diverse group of structurally related proteins that exert multiple effects on cell fate such as on cell growth and differentiation but little is known about GDF15 in these processes. Previously we observed the mature GDF15 to be associated with human prostate carcinogenesis hence prompting us to study GDF15 further. Here we report gdf15 expression both at the RNA and protein levels, in normal prostatic tissues of wild type (wt) and prostatic intraepithelial neoplasia (PIN) of transgenic (Tg) 12T-7s model mice during embryonic, postnatal, and adult prostate formation up to 15 weeks after birth. Dynamic changes in expression, at both the mRNA and protein level, correlated with cell proliferation and differentiation during distinct phases of normal mouse prostate development and alterations in the dynamics of gdf15 expression correlated with the changes in development resulting in PIN formation. Most notably mature gdf15 protein was significantly elevated during hyperplasia and PIN development. Changes in the protein levels did not always correlate well with the mRNA levels. This was more prominent during PIN than during normal prostate development suggesting that this may also be an indicator of disturbed regulation of gdf15 in PIN. We propose that gdf15 is a growth factor with dual function either promoting proliferation or growth arrest and differentiation due most likely to differences in cellular differentiation. Because of the differentiation defect in PIN its epithelium no longer responds to gdf15 by cellular growth arrest as does the normal epithelium and gdf may even stimulate proliferation. The data supports our hypothesis that GDF15 plays a role in the early stages of human prostate cancer. PMID- 17286607 TI - Human bone marrow-derived mesenchymal stem cells differentiate into epidermal like cells in vitro. AB - Human bone marrow-derived mesenchymal stem cells (hMSCs) are a population of pluripotent cells. They can differentiate into different embryonic layer cells as osteoblasts, adipocytes, chondrocytes, myoblasts, neurocytes, etc. However, there are only few reports with regard to differentiate hMSCs into epidermal cells in vitro. In this study, we want to investigate the feasibility of inducing hMSCs into epidermal-like cells under specific medium in vitro. hMSCs in specific inducing medium expressed the early markers of epidermal cell lineage, P63, cytokeratin19 (CK19), the late differentiated marker, the pan-cytokeratin, and another early marker, the beta1-integrin, which up-regulated remarkably in inducing medium. Their morphologies were changed from spindle-like fibroblastic appearances to oblate or irregular shapes under phase contrast microscopy. The hemidesmosome structure was found using the transmission electron microscope. All these data suggested that, under certain conditions, hMSCs have the potential to differentiate into epidermal-like cells. It will be of great accordance in the study of the multipotential property of hMSCs. PMID- 17286608 TI - Thalidomide-dexamethasone plus pegylated liposomal doxorubicin vs. thalidomide dexamethasone: a case-matched study in advanced multiple myeloma. AB - OBJECTIVES: Nearly all patients with multiple myeloma (MM) relapse or become refractory to front-line therapy. Several salvage therapies have been explored, but the optimal combination regimen has not been defined. We performed a case matched study comparing patients with relapsed/refractory MM receiving thalidomide-dexamethasone alone or the combination thalidomide-dexamethasone liposomal pegylated doxorubicin. METHODS: Forty-seven patients received thalidomide (100 mg/d), dexamethasone (40 mg p.o. on days 1-4 and 9-12), and pegylated liposomal doxorubicin (40 mg/m(2) on day 1 every 28 d) (ThaDD). Their clinical outcome was compared with that of 47 pair mates selected from patients treated at relapse with thalidomide (100 mg/d) and dexamethasone (40 mg p.o. on days 1-4) (Thal-Dex) and matched for age, beta2-microglobulin and previous therapy. RESULTS AND CONCLUSIONS: Overall response rate was significantly higher in ThaDD group (92% vs. 63.5%; P < 0.0001) as partial response rate (> or =PR) (75.5% vs. 59.5%; P = 0.077), very good partial response rate (> or =VGPR) (36% vs. 15%; P = 0.018) and near complete remission rate (> or =nCR) (30% vs. 10.5%; P = 0.002). Non-hematologic toxicity was similar in the two groups of patients whereas hematologic toxicity and infections were significantly higher in ThaDD patients. Median progression-free survival, event-free survival, and overall survival were significantly longer in patients receiving ThaDD than in those treated with Thal-Dex. ThaDD regimen significantly improved response rate and overall survival in comparison with Thal-Dex. Although the frequency of hematologic toxicity and infections resulted higher in ThaDD group compared with control group, they were not particularly frequent after adequate prophylaxis was added and were easily managed when occurred. PMID- 17286609 TI - Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas. AB - Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin. PMID- 17286610 TI - Dramatic age-related changes in nuclear and genome copy number in the nematode Caenorhabditis elegans. AB - The nematode Caenorhabditis elegans has become one of the most widely used model systems for the study of aging, yet very little is known about how C. elegans age. The development of the worm, from egg to young adult has been completely mapped at the cellular level, but such detailed studies have not been extended throughout the adult lifespan. Numerous single gene mutations, drug treatments and environmental manipulations have been found to extend worm lifespan. To interpret the mechanism of action of such aging interventions, studies to characterize normal worm aging, similar to those used to study worm development are necessary. We have used 4',6'-diamidino-2-phenylindole hydrochloride staining and quantitative polymerase chain reaction to investigate the integrity of nuclei and quantify the nuclear genome copy number of C. elegans with age. We report both systematic loss of nuclei or nuclear DNA, as well as dramatic age-related changes in nuclear genome copy number. These changes are delayed or attenuated in long-lived daf-2 mutants. We propose that these changes are important pathobiological characteristics of aging nematodes. PMID- 17286611 TI - Abnormalities of mitochondrial functioning can partly explain the metabolic disorders encountered in sarcopenic gastrocnemius. AB - Aging triggers several abnormalities in muscle glycolytic fibers including increased proteolysis, reactive oxygen species (ROS) production and apoptosis. Since the mitochondria are the main site of substrate oxidation, ROS production and programmed cell death, we tried to know whether the cellular disorders encountered in sarcopenia are due to abnormal mitochondrial functioning. Gastrocnemius mitochondria were extracted from adult (6 months) and aged (21 months) male Wistar rats. Respiration parameters, opening of the permeability transition pore and ROS production, with either glutamate (amino acid metabolism) or pyruvate (glucose metabolism) as a respiration substrate, were evaluated at different matrix calcium concentrations. Pyruvate dehydrogenase and respiratory complex activities as well as their contents measured by Western blotting analysis were determined. Furthermore, the fatty acid profile of mitochondrial phospholipids was also measured. At physiological calcium concentration, state III respiration rate was lowered by aging in pyruvate conditions (-22%), but not with glutamate. The reduction of pyruvate oxidation resulted from a calcium dependent inactivation of the pyruvate dehydrogenase system and could provide for the well-known proteolysis encountered during sarcopenia. Matrix calcium loading and aging increased ROS production. They also reduced the oxidative phosphorylation. This was associated with lower calcium retention capacities, suggesting that sarcopenic fibers are more prone to programmed cell death. Aging was also associated with a reduced mitochondrial superoxide dismutase activity, which does not intervene in toxic ROS overproduction but could explain the lower calcium retention capacities. Despite a lower content, cytochrome c oxidase displayed an increased activity associated with an increased n-6/n-3 polyunsaturated fatty acid ratio of mitochondrial phospholipids. In conclusion, we propose that mitochondria obtained from aged muscle fibers display several functional abnormalities explaining the increased proteolysis, ROS overproduction and vulnerability to apoptosis exhibited by sarcopenic muscle. These changes appear to be related to modifications of the fatty acid profile of mitochondrial lipids. PMID- 17286612 TI - Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence. AB - The adaptive immune response requires waves of T-cell clonal expansion on contact with altered self and contraction after elimination of antigen. In the case of persisting antigen, as occurs for example in cytomegalovirus or Epstein-Barr virus infection, this critical process can become dysregulated and responding T cells enter into a dysfunctional senescent state. Longitudinal studies suggest that the presence of increased numbers of such T-cells is a poor prognostic factor for survival in the very elderly. Understanding the nature of the defects in these T-cells might facilitate intervention to improve immunity in the elderly. The process of clonal expansion under chronic antigenic stress can be modelled in vitro using continuously cultured T-cells. Here, we have used cDNA array technology to investigate differences in gene expression in a set of five different T-cell clones at early, middle and late passage in culture. Differentially expressed genes were confirmed by real-time polymerase chain reaction, and relationships between these assessed using Ingenuity Systems evidence-based association analysis. Several genes and chemokines related to induction of apoptosis and signal transduction pathways regulated by transforming growth factor beta (TGFbeta), epidermal growth factor (EGF), fos and beta-catenin were altered in late compared to early passage cells. These pathways and affected genes may play a significant role in driving the cellular senescent phenotype and warrant further investigation as potential biomarkers of aging and senescence. These genes may additionally provide targets for intervention. PMID- 17286614 TI - Lessons from the CAESAR Study: calcineurin inhibitors--can't live with them and can't live without them. PMID- 17286615 TI - Invasive pneumococcal disease in solid organ transplant recipients--10-year prospective population surveillance. AB - Prospective population-based surveillance to assess the incidence and impact of invasive pneumococcal disease (IPD) in organ transplant patients is lacking. By using a population-based Invasive Bacterial Diseases Network surveillance program, we studied the incidence, clinical significance, serotypes and antimicrobial resistance pattern of IPD in a large cohort of adult transplant patients and the general population. Streptococcus pneumoniae isolates and patient data were collected prospectively from 1995 to 2004. We identified 21 cases of IPD (based on sterile-site isolates) in our organ transplant population over a 10-year period. This translated to an incidence rate of 146 infections per 100,000 persons per year. This compared to an incidence of 11.5 per 100,000 persons per year in the general population (R(R)=12.8; 95% CI 8.1-19.9, p<0.00001). If nonsterile-site isolates (respiratory tract) were included, the incidence rate in transplant patients was 419 of 100 000 persons per year. Serotypes 23F and 22F were most common, and 85.0% had a serotype included in the 23-valent pneumococcal vaccine. The antimicrobial resistance rates were high, especially for penicillin and trimethoprim-sulfamethoxazole (TMP/SMX), but were not significantly different from the general population. Solid organ transplant recipients are at significantly greater risk for IPD than the general population. Preventative strategies are necessary. PMID- 17286616 TI - Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection. AB - The localization and significance of regulatory T cells (Treg) in allograft rejection is of considerable clinical and immunological interest. We analyzed 80 human renal transplant biopsies (including seven donor biopsies) with a double immunohistochemical marker for the Treg transcription factor FOXP3, combined with a second marker for CD4 or CD8. Quantitative FOXP3 cell counts were performed and analyzed for clinical and pathologic correlates. FOXP3(+) cells were present in the interstitium in acute cellular rejection (ACR) type I and II, at a greater density than in acute humoral rejection or CNI toxicity (p < 0.01). Most FOXP3(+) cells were CD4(+) (96%); a minority expressed CD8. FOXP3(+)CD4(+) cells were concentrated in the tubules (p < 0.001), suggesting a selective attraction or generation at that site. Considering only patients with ACR, a higher density of FOXP3(+) correlated with HLA class II match (p = 0.03), but paradoxically with worse graft survival. We conclude that infiltration of FOXP3(+) cells occurs in ACR to a greater degree than in humoral rejection, however, within the ACR group, no beneficial effect on outcome was evident. Tregs concentrate in tubules, probably contributing to FOXP3 mRNA in urine; the significance and pathogenesis of 'Treg tubulitis' remains to be determined. PMID- 17286618 TI - Primary nonfunction (PNF) in the MELD Era: An SRTR database analysis. AB - PNF following liver transplantation (LT) is an infrequent but life-threatening complication. Liver allocation under MELD is based upon recipient severity of illness, a known risk factor for the occurrence of PNF. The incidence of PNF since the application of MELD has not previously been reported. The SRTR database was studied since inception of MELD until September 2004 for all adult recipients of deceased donor LT. PNF was defined as graft loss or death within 14 days of LT secondary to PNF or without defined cause. A total of 10545 transplants met inclusion criteria and PNF occurred in 613 (5.81%) of recipients. Univariate analysis demonstrated donor age, serum creatinine >1.5 mg/mL, hypertension and CVA as risk factors for PNF. Recipient factors included life support, mechanical ventilation, use of inotropes, hemodialysis, initial status 1 and use of a shared transplant. In the multivariate model only donor age and recipient serum creatinine, bilirubin, on life support and status 1 at transplant were significant risk factors for PNF. In this analysis of PNF in the MELD era the incidence of PNF does not appear to have increased from prior reports. Risk factors for PNF are related to donor age and severity of recipient illness. PMID- 17286617 TI - Depletion of CD8 memory T cells for induction of tolerance of a previously transplanted kidney allograft. AB - Heterologous immunologic memory has been considered a potent barrier to tolerance induction in primates. Induction of such tolerance for a previously transplanted organ may be more difficult, because specific memory cells can be induced and activated by a transplanted organ. In the current study, we attempted to induce tolerance to a previously transplanted kidney allograft in nonhuman primates. The conditioning regimen consisted of low dose total body irradiation, thymic irradiation, antithymocyte globulin, and anti-CD154 antibody followed by a brief course of a calcineurin inhibitor. This regimen had been shown to induce mixed chimerism and allograft tolerance when kidney transplantation (KTx) and donor bone marrow transplantation (DBMT) were simultaneously performed. However, the same regimen failed to induce mixed chimerism when delayed DBMT was performed after KTx. We found that significant levels of memory T cells remained after conditioning, despite effective depletion of naive T cells. By adding humanized anti-CD8 monoclonal antibody (cM-T807), CD8 memory T cells were effectively depleted and these recipients successfully achieved mixed chimerism and tolerance. The current studies provide 'proof of principle' that the mixed chimerism approach can induce renal allograft tolerance, even late after organ transplantation if memory T-cell function is adequately controlled. PMID- 17286619 TI - The impact of treatment of portopulmonary hypertension on survival following liver transplantation. AB - Pulmonary hypertension in the setting of cirrhosis and portal hypertension is known as portopulmonary hypertension (PPHTN). Moderate or severe PPHTN is uncommon, but has a poor prognosis and is considered to be a contraindication to liver transplantation. We assessed the impact of vasodilation therapy on pulmonary hemodynamics and outcome after liver transplant in these patients. Eighty-six patients evaluated for liver transplant between 1997 and 2005 had an estimated right ventricular systolic pressure >40 mm Hg or a clinical suspicion of PPHTN. Right heart catheterization confirmed PPHTN in 30 patients (ten mild, eight moderate, and 12 severe). Sixteen of the 20 with moderate-to-severe pulmonary hypertension (mPAP >or= 35) were otherwise considered suitable liver transplant candidates and were treated with vasodilation therapy. mPAP fell to less than 35 mm Hg in 12 patients (75%) and 11 of them then underwent orthotopic liver transplantation. One- and five-year survivals in the transplanted patients were 91% and 67%, respectively. Nine of 11 were off vasodilator therapy after a median of 9.2 months following transplantation. None of the patients who failed vasodilator therapy survived (median survival, 8 months). Effective pharmacologic control of PPHTN before liver transplant is associated with excellent posttransplant survival that is similar to patients transplanted for other indications. PMID- 17286620 TI - Acute pyelonephritis represents a risk factor impairing long-term kidney graft function. AB - Urinary tract infections (UTIs) and acute pyelonephritis (APN) often occur after renal transplantation, but their impact on graft outcome is unclear. One hundred and seventy-seven consecutive renal transplantations were investigated to evaluate the impact of UTIs and APN on graft function. The cumulative incidence of UTIs was 75.1% and that of APN was 18.7%. UTIs occurred mainly during the first year after transplantation and Escherichia coli, Pseudomonas aeruginosa and Enteroccocus sp. were the most frequent pathogens identified. The risk of developing APN was higher in female (64%) than in male recipients, and was correlated with the frequency of recurrent UTIs (p < 0.0001) and rejection episodes (p = 0.0003). APN did not alter graft or recipient survival, however, compared to patients with uncomplicated UTIs, patients with APN exhibited both a significant increase in serum creatinine and a decrease in creatinine clearance, already detected after 1 year (aMDRD-GFR: APN: 39.5 +/- 12.5; uncomplicated UTI: 54.6 +/- 21.7 mL/min/1.73 m(2), p < 0.01) and still persistent ( approximately - 50%) 4 years after transplantation. Multivariate analysis revealed that APN represents an independent risk factor associated with the decline of renal function (p = 0.034). Therefore, APN may be associated with an enduring decrease in renal graft function. PMID- 17286621 TI - Engaging the private sector for tuberculosis control: much advocacy on a meagre evidence base. PMID- 17286622 TI - Tuberculosis in intra-urban settings: a Bayesian approach. AB - OBJECTIVE: To model the effect of socio-economic deprivation and a few transmission-related indicators of the tuberculosis (TB) incidence at small area level, to discuss the potential of each indicator in targeting places for developing preventive action. METHODS: Ecological spatial study of TB incidence in Olinda, a city in the north-east of Brazil, during the period 1996-2000. Three socio-economic indicators (mean number of inhabitants per household; percentage of heads of household with <1 year's formal education; percentage of heads of households with monthly income lower than the minimum wage) and two transmission related indicators (number of cases of retreatment; number of households with more than one case during the period under study), all calculated per census tract, were used. We adopted four different full hierarchical Bayesian models to estimate the relative risk of the occurrence of TB via Markov chain Monte Carlo. RESULTS: The best specified model includes all the selected covariates and the spatially structured random effect. The gain in goodness-of-fit statistic when the spatial structure was included confirms the clustered spatial pattern of disease and poverty. In this model, the covariates within the non-zero credibility interval were the number of persons per house, the number of cases of retreatment and the number of households with more than one case (all with relative risk > or = 1.8) in each census tract. CONCLUSIONS: The possibility to estimate in the same framework both the contribution of covariates at ecological level and the spatial pattern should be encouraged in epidemiology, and may help with establishing Epidemiological Surveillance Systems on a territorial basis, that allows rational planning of interventions and improvement of the Control Programme effectiveness. PMID- 17286623 TI - The Third Stroke Registry in Tartu, Estonia, from 2001 to 2003. AB - OBJECTIVES: The main goal of the Third Stroke Registry in Tartu was to determine the incidence and 28-day case-fatality of first-ever stroke in an Estonian population. SUBJECTS AND METHODS: Stroke registry was conducted from 1 December 2001 to 30 November 2003. RESULTS: The registry included 451 patients. The incidence rate of first-ever stroke age-standardized to the European population was 188/100,000. Among younger patients, the rates for men dominated. The incidence among men aged 0-44 years was 18/100,000, for women 9/100,000. In the age group 45-54 years, the corresponding rates were 143/100,000 and 98/100,000 respectively. The overall 28-day case-fatality rate was 26%. CONCLUSIONS: The total stroke incidence in Tartu is comparable with other European studies, but the rates for younger patients are higher. This may be associated with lower quality of life, less attention to public health, high prevalence and/or poor control of stroke risk factors. The 28-day case-fatality is somewhat higher than in other European centres. PMID- 17286624 TI - Long-term safety and tolerability of oxcarbazepine in painful diabetic neuropathy. AB - BACKGROUND: Painful diabetic neuropathy is a common complication of diabetes and often resistant to treatment with standard analgesics. Treatment of diabetic neuropathy with antiepileptic drugs may provide pain relief. AIM: To evaluate the long-term safety and tolerability of oxcarbazepine in two studies investigating the treatment of diabetic neuropathy. OBJECTIVES: Patients with diabetes and a history of neuropathic pain were included. Study 1 was a multicenter, open-label study comprising a screening and 12-month treatment phase. Study 2 was a multicenter, open-label extension to a double-blind, randomized study. Oxcarbazepine was initiated at 300 mg/day and titrated over 4 weeks to tolerability or a maximum dose of 900 mg b.i.d. Safety was assessed by monitoring adverse events (AEs), serious AEs (SAEs), hematology, blood chemistry, urinalysis values, and vital signs. RESULTS: Adverse events were most frequently reported in the nervous and gastrointestinal systems; 20.5% and 21.6% of patients withdrew because of AEs in study 1 and study 2, respectively. SAEs were reported in 13.7% and 14.4% of patients in study 1 and study 2, respectively. CONCLUSIONS: Long term treatment with oxcarbazepine is generally well tolerated in patients with painful diabetic neuropathy. Rapid titration of oxcarbazepine may be responsible for discontinuations resulting from AEs during early stages of treatment. PMID- 17286625 TI - Qualitative data analysis for health services research: developing taxonomy, themes, and theory. AB - OBJECTIVE: To provide practical strategies for conducting and evaluating analyses of qualitative data applicable for health services researchers. DATA SOURCES AND DESIGN: We draw on extant qualitative methodological literature to describe practical approaches to qualitative data analysis. Approaches to data analysis vary by discipline and analytic tradition; however, we focus on qualitative data analysis that has as a goal the generation of taxonomy, themes, and theory germane to health services research. PRINCIPLE FINDINGS: We describe an approach to qualitative data analysis that applies the principles of inductive reasoning while also employing predetermined code types to guide data analysis and interpretation. These code types (conceptual, relationship, perspective, participant characteristics, and setting codes) define a structure that is appropriate for generation of taxonomy, themes, and theory. Conceptual codes and subcodes facilitate the development of taxonomies. Relationship and perspective codes facilitate the development of themes and theory. Intersectional analyses with data coded for participant characteristics and setting codes can facilitate comparative analyses. CONCLUSIONS: Qualitative inquiry can improve the description and explanation of complex, real-world phenomena pertinent to health services research. Greater understanding of the processes of qualitative data analysis can be helpful for health services researchers as they use these methods themselves or collaborate with qualitative researchers from a wide range of disciplines. PMID- 17286626 TI - On the ocular refractive components: the Reykjavik Eye Study. AB - PURPOSE: To study the correlation between ocular refraction and the refractive components (corneal power, lens power and axial length) in a population-based sample of normal subjects. METHODS: We analysed the refractive and biometric findings for 723 right eyes (325 males and 398 females) comprising a population based random sample of citizens 55 years and older participating in the Reykjavik Eye Study. Measurements of refraction, corneal curvature (by keratometry), anterior chamber depth, lens thickness and axial length (all by ultrasound biometry) were used to calculate crystalline lens power. The correlation and regression between refraction and ocular refractive components (corneal power, anterior chamber depth, lens power and axial length) were studied by distributional statistical methods. RESULTS: Refraction (spherical equivalent) showed a significant negative correlation with axial length (r = -0.59, P < 0.0001), lens power (r = -0.26, P < 0.0001) and corneal power (r = -0.16, P < 0.0001). There were significant negative correlations between axial length and corneal power (r = -0.44, P < 0.0001) and between axial length and lens power (r = -0.44, P < 0.0001). Based on multiple linear regression analysis, refraction could be correlated with corneal power, lens power and axial length in combination with a correlation coefficient of 0.98 (P < 0.0001). CONCLUSION: This study confirms that ocular refraction is statistically significantly correlated with not only axial length but also lens power and (to a lesser extent) corneal power. The variation and correlations of crystalline lens power were considerable -- possibly indicating this component's modulatory effect on ocular refraction during growth. We conclude the refractive error of the eye to be a multifactorial condition involving a complex interplay between the cornea, the lens and the length of the eye. PMID- 17286627 TI - Lovastatin attenuates nerve injury in an animal model of Guillain-Barre syndrome. AB - Statins, widely used as clinically effective inhibitors of 3-hydroxy-3 methylglutaryl coenzyme A reductase, exhibit anti-inflammatory properties that may be of therapeutic benefit for the management of some neurological disorders. In this study, a short-term course of lovastatin treatment is shown to markedly inhibit the development of experimental autoimmune neuritis (EAN) in the absence of hepatotoxic or myotoxic complications. Independent of cholesterol reduction, lovastatin treatment prevented EAN-induced peripheral nerve conduction deficits and morphologic nerve injury. Co-administration with mevalonate neutralized the prophylactic effects of lovastatin. When administered therapeutically, lovastatin significantly shortened the disease course. Autoreactive immunity, measured in vitro by myelin-stimulated proliferation of splenocytes, was significantly diminished by in vivo lovastatin treatment. Th1-dominant immune responses, measured by cytokine profiling, however, were not affected by lovastatin. Sciatic nerves of lovastatin-treated immunized rats showed markedly reduced levels of cellular infiltrates. Treating peripheral nerve endothelial monolayers with lovastatin significantly inhibited the in vitro migration of autoreactive splenocytes. Together, these data demonstrate that a short-term course of lovastatin attenuates the development and progression of EAN in Lewis rats by limiting the proliferation and migration of autoreactive leukocytes. PMID- 17286628 TI - Truncated tyrosine kinase B brain-derived neurotrophic factor receptor directs cortical neural stem cells to a glial cell fate by a novel signaling mechanism. AB - During development of the mammalian cerebral cortex neural stem cells (NSC) first generate neurons and subsequently produce glial cells. The mechanism(s) responsible for this developmental shift from neurogenesis to gliogenesis is unknown. Brain-derived neurotrophic factor (BDNF) is believed to play important roles in the development of the mammalian cerebral cortex; it enhances neurogenesis and promotes the differentiation and survival of newly generated neurons. Here, we provide evidence that a truncated form of the BDNF receptor tyrosine kinase B (trkB-t) plays a pivotal role in directing embryonic mouse cortical NSC to a glial cell fate. Expression of trkB-t promotes differentiation of NSC toward astrocytes while inhibiting neurogenesis both in cell culture and in vivo. The mechanism by which trkB-t induces astrocyte genesis is not simply the result of inhibition of full-length receptor with intrinsic tyrosine kinase activity signaling. Instead, binding of BDNF to trkB-t activates a signaling pathway (involving a G-protein and protein kinase C) that induced NSC to become glial progenitors and astrocytes. Thus, the increased expression of trkB-t in the embryonic cerebral cortex that occurs coincident with astrocyte production plays a pivotal role in the developmental transition from neurogenesis to gliogenesis. Our findings suggest a mechanism by which a single factor (BDNF) regulates the production of the two major cell types in the mammalian cerebral cortex. PMID- 17286629 TI - Updates from the British Association of Dermatologists 86th annual meeting, 4-7 July 2006, Manchester, U.K. AB - Here we provide a synopsis of the main clinical and research advances in clinical, epidemiological and biological dermatology that were presented at the meeting of the British Association of Dermatologists (BAD) held during 4-7 July 2006, in Manchester, U.K. Only the more important advances or summaries of findings are mentioned. The meeting was held at the Manchester International Conference Centre (Fig. 1). The annual dinner was held at Manchester Town Hall, in the Great Hall decorated with magnificent murals by Ford Madox Brown, with Dr Susan Burge as host. PMID- 17286630 TI - Treatment of axillary hyperhidrosis with botulinum toxin type A reconstituted in lidocaine or in normal saline: a randomized, side-by-side, double-blind study. AB - BACKGROUND: Botulinum toxin type A represents a safe and effective treatment for primary axillary hyperhidrosis. One of the most troublesome disadvantages associated with this therapy is pain at the injection sites. Reconstitution of botulinum toxin A in a solution of lidocaine could be an easy alternative procedure to reduce the discomfort associated with those injections. However, the current recommendations are that botulinum toxin A should be reconstituted in normal saline. OBJECTIVES: To compare the efficacy and tolerance profile of saline-diluted botulinum toxin A and lidocaine-diluted botulinum toxin A in patients with axillary hyperhidrosis. METHODS: In a double-blind, side-by-side, controlled, randomized clinical trial, 29 patients were injected with 100 mouse units of botulinum toxin A (Botox); Allergan Pharmaceuticals Ireland, Westport, Ireland) reconstituted in lidocaine into one axilla and with the same dosage of the toxin, reconstituted in an equal volume of saline, into the other axilla. The patients were followed up for 8 months. Quantification of sweat production was performed by iodine-starch tests and by the patients' own rating of sweating. The intensity of pain associated with the botulinum toxin intracutaneous injections was self-assessed by the patients and was evaluated using a 100-mm visual analogue scale. RESULTS: Botulinum toxin A diluted in normal saline and botulinum toxin A diluted in lidocaine were similarly effective in terms of control of onset of sweat production, duration of effect and subjective percentage of mean decrease in sweating. Both treatments were well tolerated, and there were no lasting or severe adverse effects. However, the mean +/- SD pain score during the procedure was significantly lower in the axillae treated with lidocaine reconstituted botulinum toxin than in the axillae treated with saline reconstituted botulinum toxin (29.3 +/- 20.1 vs. 47.5 +/- 24.0; P = 0.0027). CONCLUSIONS: Short- and long-term results show the equal effectiveness of botulinum toxin A reconstituted in saline or in lidocaine. However, because injections of botulinum toxin A reconstituted in lidocaine are associated with significantly reduced pain, lidocaine-reconstituted botulinum toxin A may be preferable for treating axillary hyperhidrosis. PMID- 17286632 TI - Do we need a revised public health policy on sun exposure? PMID- 17286633 TI - Bortezomib-associated rash: a new recognizable and avoidable side-effect. PMID- 17286634 TI - Folliculotropic Sezary syndrome: a new variant of cutaneous T-cell lymphoma. PMID- 17286635 TI - Successful treatment of scalp actinic keratoses with photodynamic therapy using ambient light. PMID- 17286636 TI - Primary cutaneous peripheral T-cell lymphoma, unspecified, that completely regressed after skin biopsy. PMID- 17286637 TI - Examination of the association between syringe exchange program (SEP) dispensation policy and SEP client-level syringe coverage among injection drug users. AB - AIM: To determine whether syringe exchange programs' (SEPs) dispensation policy is associated with syringe coverage among SEP clients. DESIGN: Cross-sectional samples of SEPs and their clients. SETTING: SEPs in California, USA. PARTICIPANTS: Twenty-four SEPs and their injection drug using (IDU) clients (n = 1576). MEASUREMENTS: Clients were classified as having adequate syringe coverage if they received at least as many syringes from the SEP as their self-reported injections in the last 30 days. SEPs were classified based on their syringe dispensation policy. Dispensation schemes ranging from least restrictive to most are: unlimited needs-based distribution; unlimited one-for-one exchange plus a few additional syringes; per visit limited one-for-one plus a few additional syringes; unlimited one-for-one exchange; and per visit limited one-for-one exchange. FINDINGS: Adequate syringe coverage among SEP clients by dispensation policy is as follows: unlimited needs-based distribution = 61%; unlimited one-for one plus = 50%; limited one-for-one plus = 41%; unlimited one-for-one = 42%; and limited one-for-one = 26%. In multivariate analysis, adequate syringe coverage was significantly higher for all dispensation policies compared to per visit limited one-for-one exchange. Using propensity scoring methods, we compared syringe coverage by dispensation policies while controlling for client-level differences. Providing additional syringes above one-for-one exchange (50% versus 38%, P = 0.009) and unlimited exchange (42% versus 27%, P = 0.05) generally resulted in more clients having adequate syringe coverage compared to one-for-one exchange and per visit limits. CONCLUSION: Providing less restrictive syringe dispensation is associated with increased prevalence of adequate syringe coverage among clients. SEPs should adopt syringe dispensation policies that provide IDUs sufficient syringes to attain adequate syringe coverage. PMID- 17286638 TI - Alcohol and the preventive paradox: serious harms and drinking patterns. AB - AIMS: The preventive paradox prevails if the majority of alcohol problems accrue to the lesser-drinking majority of population, not to heavy drinkers. Evidence for the paradox has been criticized for being based on self-report. The aim was to examine whether the paradox also applies to deaths and hospital admissions. DESIGN: Data from four surveys representing the Finnish population aged 15-69 years in 1969, 1976, 1984 and 1992 were pooled; those from 1969, 1976 and 1984 (n = 6726) to study alcohol-related hospital admissions and alcohol-related deaths, and those from 1984 and 1992 (n = 5558) to study self-reported problems. The former data were linked with register data on hospital admission and death up to the end of 2002. METHODS: Comparisons were made separately for men and women (1) between the 10% of population with the highest average alcohol consumption and the remaining 90% of drinkers and (2) between those who reported and those who did not report drinking to intoxication. RESULTS: A total of 3025 men and 2693 women were available for the study of self-reported problems and 2945 men and 2615 women for deaths and hospital admissions. Seventy per cent of all self reported problems, 70% of alcohol-related hospitalizations, 64% of alcohol related deaths and 64% of the premature life-years lost before the age of 65 occurred among the 90% of men consuming less. The respective figures for women were 64%, 60%, 93% and 98%. Drinking five or more drinks per occasion was related to more harm than not drinking that much. CONCLUSIONS: In men, the "prevention paradox" appears to apply to a broadly similar degree to hospitalizations and deaths as self-report alcohol-related problems; in women the phenomenon was apparent to a greater degree for deaths than for other markers of harm. PMID- 17286639 TI - The acute effects of exercise on cigarette cravings, withdrawal symptoms, affect and smoking behaviour: a systematic review. AB - AIM: To review the effects of a single session of exercise on cigarette cravings, withdrawal symptoms and smoking behaviour. METHODS: A systematic search and critical appraisal of all 14 relevant studies. RESULTS: All 12 studies that compared a bout of exercise with a passive condition reported a positive effect on cigarette cravings, withdrawal symptoms and smoking behaviour. Two other studies that compared two intensities of exercise revealed no differences in outcomes. Single and multi-item measures of cigarette cravings, withdrawal symptoms and negative affect decreased rapidly during exercise and remained reduced for up to 50 minutes after exercise. Effect sizes for seven studies that assessed "strength of desire to smoke" showed a mean reduction, 10 minutes after exercise, of 1.1 (SD 0.9). Four studies reported a two- to threefold longer time to the next cigarette following exercise. Cravings and withdrawal symptoms were reduced with an exercise intensity from as high as 60-85% heart rate reserve (HRR) (lasting 30-40 minutes) to as low as 24% HRR (lasting 15 minutes), and also with isometric exercise (for 5 minutes). All but one study involved participants temporarily abstaining for the purposes of the experiment. Distraction was probably not the primary reason for the effects. CONCLUSIONS: Relatively small doses of exercise should be recommended as an aid to managing cigarette cravings and withdrawal symptoms. Further research to understand the mechanisms involved, such as stress reduction or neurobiological mechanisms, could lead to development of more effective and practical methods to reduce withdrawal phenomena. PMID- 17286640 TI - Does childhood sexual abuse have an effect on young adults' nicotine disorder (dependence or withdrawal)? Evidence from a birth cohort study. AB - AIMS: To examine whether there is evidence of an independent association between childhood sexual abuse (CSA) and nicotine disorder in youth and to explore the mechanisms underlying this association in a prospective cohort study. DESIGN: Birth cohort study followed-up to 21 years. SETTING: One of two major obstetric hospitals in Brisbane, Australia. PARTICIPANTS: The Mater-University of Queensland Study of Pregnancy involves a prospective birth cohort from a population-based sample involving 7223 singletons whose mothers were enrolled between 1981 and 1984 at the first antenatal visit. The present cohort consisted of a subgroup of 2571 youth who completed the life-time version of the Composite International Diagnostic Interview--computerized version (CIDI-Auto) at the 21 year follow-up. MEASUREMENTS: Nicotine disorder was measured based on Diagnostic and Statistical Manual version IV (DSM-IV) diagnostic criteria and measures of CSA, including retrospective self-reports of rape, were obtained at 21 years. Results Of 2571 young adults, 16.6% met the criteria for either dependence (12.8%) or withdrawal (8.5%). Non-penetrative sexual abuse was reported by 15.5% of respondents and 8.0% reported penetrative sexual abuse. For any types of sexual abuse including non-penetrative, penetrative and self-reported rape before age 16 years, young adults had significantly higher rates of nicotine disorder than young adults who did not experience CSA. This relationship was independent and appeared direct after adjustment for a range of potential confounding and mediating factors. CONCLUSIONS: This study shows that CSA is associated with young adult nicotine disorder. The results extend the public health significance of findings in this area and highlight the importance of not only intensifying public health efforts to address substance use problems among those who have experienced CSA, but of early intervention, so that emerging risky behaviours may be targeted in the earliest stages. PMID- 17286642 TI - Trajectories of adolescent alcohol and cannabis use into young adulthood. AB - BACKGROUND: Both alcohol and cannabis use carry health risks. Both are commonly initiated in adolescence. To date little research has described trajectories of adolescent cannabis or alcohol use or compared their respective consequences in young adulthood. METHODS: The design was a 10-year eight-wave cohort study of a state-wide community sample of 1943 Victorians initially aged 14-15 years. Moderate- and high-risk alcohol use was defined according to total weekly alcohol consumption. Moderate- and high-risk cannabis use were defined as weekly and daily use, respectively. RESULTS: Around 90% of young adults used either alcohol or cannabis. Although an association existed between alcohol and cannabis use, there was a tendency for heavy users to use one substance predominantly at any one time. Weekly or more frequent cannabis use in the absence of moderate-risk alcohol use in teenagers predicted a sevenfold higher rate of daily cannabis use in young adults but only a twofold increase in high-risk alcohol use. Conversely, moderate-risk adolescent alcohol use in the absence of weekly cannabis predicted an approximately threefold increased rate of both high-risk drinking and daily cannabis use in young adulthood. Selective heavy cannabis use in both adolescence and young adulthood was associated with greater illicit substance use and poorer social outcomes in young adulthood than selective alcohol use. CONCLUSIONS: Heavier teenage cannabis users tend to continue selectively with cannabis use. Considering their poor young adult outcomes, regular adolescent cannabis users appear to be on a problematic trajectory. PMID- 17286641 TI - Concurrent buprenorphine and benzodiazepines use and self-reported opioid toxicity in opioid substitution treatment. AB - AIMS: To examine concurrent buprenorphine and benzodiazepine consumption and to compare opioid toxicity symptoms induced by methadone and buprenorphine, examining factors associated with the reporting of these symptoms. DESIGN: Self report cross-sectional survey. SETTING: Five needle syringe programmes and five opioid substitution treatment services in Melbourne, Australia. PARTICIPANTS: A total of 250 people who had experience with methadone or buprenorphine. Eligibility criteria were current or previous methadone or buprenorphine use. MEASUREMENTS: Structured questionnaire covering: demographic characteristics; current treatment and drug use; concurrent use of buprenorphine and benzodiazepines, including route of administration and source of medications; and opioid toxicity symptoms reported in association with methadone and buprenorphine consumption. FINDINGS: Of those reporting buprenorphine use, two-thirds reported concurrent benzodiazepine use, with a median dose reported of 30 mg diazepam equivalents. A greater number of opioid toxicity symptoms were reported in relation to methadone consumption compared with buprenorphine. Those reporting opioid toxicity with buprenorphine were more likely to report intravenous use compared with those reporting opioid toxicity with methadone. CONCLUSIONS: The risk of opioid toxicity appeared greater with methadone compared with buprenorphine, despite high levels of benzodiazepine consumption and injection being reported in relation to buprenorphine use. The prevalence of buprenorphine injection and the normalization of methadone-induced sedation are two findings that merit further investigation. Establishing recommendations as to the safest and most effective way to manage benzodiazepine-using people in opioid substitution treatment is necessary for the optimization of treatment for opioid dependence in polydrug-using individuals. PMID- 17286643 TI - A Swedish alcohol ignition interlock programme for drink-drivers: effects on hospital care utilization and sick leave. AB - AIMS: This project evaluates health outcomes following an alcohol ignition interlock programme (AIIP) by assessing hospital care utilization and sick-leave register data relative to controls with revoked licences, but with no comparable opportunity to participate in an AIIP. SETTING: In Sweden, driving while impaired (DWI) offenders can now select voluntarily a 2-year AIIP in lieu of 12 months' licence revocation. The AIIP includes regular medical check-ups designed to alter alcohol use. DESIGN: The study is a quasi-experimental intent-to-treat design; accordingly, the intervention group includes 48% of the participants who were dismissed from the AIIP before completion. FINDING: The control group (865 individuals) showed increased hospital care and sick leave after licence revocation following the DWI. Among the 1266 people in the AIIP, however, significantly fewer needed hospital care relative to controls, and relative to their own care utilization before the DWI offence. This occurred whether care reflected all diagnosis or only alcohol-related diagnosis. Also, sick-leave data showed significantly fewer AIIP group individuals using sick leave relative to the control group, and relative to their own pre-treatment period. These significant health benefits disappear in the post-treatment period. However, among those who actually do complete the entire AIIP, sustained positive health effects are observed 3 and 4 years after the DWI offence. CONCLUSIONS: Voluntary participation in an AIIP has favourable effects with less need for hospital care or sick leave. This is probably linked to reduced alcohol consumption during the programme and to the ability to continue driving. PMID- 17286644 TI - New terminology of the cardiac walls and new classification of Q-wave M infarction based on cardiac magnetic resonance correlations. PMID- 17286646 TI - Interatrial block: a novel risk factor for embolic stroke? AB - BACKGROUND: Interatrial block (IAB; P wave > or = 110 ms) is highly prevalent and is strongly associated with atrial tachyarrhythmias and left atrial dysfunction, making it a potential embolic risk. METHODS AND RESULTS: Among 293 neurological admissions over 2 years, 85 patients were diagnosed with embolic strokes and 208 with nonembolic strokes. Patients were then matched for stroke risk factors and evaluated for IAB. Eighty-eight percent of probable embolic stroke patients showed sinus rhythm, demonstrating a 61% IAB prevalence. Only hypertension (P < 0.001; r = 0.3) and IAB (P < 0.006; r = 0.2) were significant and directly correlated. CONCLUSION: IAB could indeed be a novel risk for embolic strokes and further investigation is warranted. PMID- 17286645 TI - Comparison of different methods of ST segment resolution analysis for prediction of 1-year mortality after primary angioplasty for acute myocardial infarction. AB - BACKGROUND: Resolution of ST segment elevation corresponds with myocardial tissue reperfusion and correlates with clinical outcome after ST elevation myocardial infarction. Simpler method evaluating the extent of maximal deviation persisting in a single ECG lead was an even stronger mortality predictor. Our aim was to evaluate and compare prognostic accuracy of different methods of ST segment elevation resolution analysis after primary percutaneous coronary intervention (PCI) in a real-life setting. METHODS: Paired 12-lead ECGs were analyzed in 324 consecutive and unselected patients treated routinely with primary PCI in a single high-volume center. ST segment resolution was quantified and categorized into complete, partial, or none, upon the (1) sum of multilead ST elevations (sumSTE) and (2) sum of ST elevations plus reciprocal depressions (sumSTE+D); or into the low-, medium-, and high-risk groups by (3) the single-lead extent of maximal postprocedural ST deviation (maxSTE). RESULTS: Complete, partial, and nonresolution groups by sumSTE constituted 39%, 40%, and 21% of patients, respective groups by sumSTE+D comprised 40%, 39%, and 21%. The low-, medium-, and high-risk groups constituted 43%, 32%, and 25%. One-year mortality rates for rising risk groups by sumSTE were 4.7%, 10.2%, and 14.5% (P = 0.049), for sumSTE+D 3.8%, 9.6%, and 17.6% (P = 0.004) and for maxSTE 5.1%, 6.7%, and 18.5% (P = 0.001), respectively. After adjustment for multiple covariates only maxSTE (high vs low-risk, odds ratio [OR] 3.10; 95% confidence interval [CI] 1.11-8.63; P = 0.030) and age (OR 1.07; 95% CI 1.02-1.11; P = 0.002) remained independent predictors of mortality. CONCLUSIONS: In unselected population risk stratifications based on the postprocedural ST resolution analysis correlate with 1-year mortality after primary PCI. However, only the single-lead ST deviation analysis allows an independent mortality prediction. PMID- 17286647 TI - Potential factors that affect electrocardiographic progression of interatrial block. AB - INTRODUCTION: Interatrial block (IAB; P wave > or = 110 ms) is associated with atrial tachyarrhythmias and left atrial electromechanical dysfunction. This subtle abnormality is highly prevalent and may exist as partial (pIAB) or advanced IAB (aIAB). Indeed, theoretically pIAB could progress to aIAB with worsening interatrial conduction over time. However, this has been poorly investigated. We retrospectively appraised this phenomenon and also evaluated the influence of common clinical factors such as coronary artery disease (CAD), hypertension (HTN), and use of antihypertensive medications. METHODS: Between January 2003 and June 2004, 27 patients who had aIAB on routine 12-lead ECGs were identified. Past serial ECGs of each patient were evaluated for evidence of change in IAB type. Medical records of respective patients were then reviewed for HTN, type of antihypertensive medication used, and other common comorbidities. RESULTS: Median progression time from pIAB to aIAB was shorter (42 months; mean +/- SD = 39.2 +/- 30.5) compared to that of normal P wave (P-normal) to aIAB (66 months; mean +/- SD = 64.2 +/- 25.6). Use of angiotensin-converting enzyme inhibitors (ACEIs) appeared to significantly delay the progression time in patients who progressed from pIAB to aIAB (50.1 +/- 28.3 vs 10 +/- 10.4 months; P = 0.04). Beta-adrenergic blocker use alone did not significantly affect either progression time but when used in conjunction with ACEIs, appeared to slow such progression. CONCLUSION: Progression time from pIAB to aIAB is shorter compared to that of P-normal to aIAB. Given the consequences of IAB, awareness of such progression could be important for clinicians in anticipating potential sequelae. PMID- 17286648 TI - Impaired functional status and echocardiographic abnormalities signifying global dysfunction enhance the prognostic significance of previously unrecognized myocardial infarction detected by electrocardiography. AB - BACKGROUND: The relationship between electrocardiographic unrecognized myocardial infarction (UMI), abnormal functional status, echocardiographic abnormalities, and mortality has not been evaluated. METHODS: A population-based random sample of 2042 Olmsted County residents, age > or = 45 years, was studied by self administered questionnaire, chart review, ECG and echocardiogram, and 5 year follow-up for all-cause mortality. UMI (n = 81) was diagnosed if ECG-MI criteria were met without previous documented myocardial infarction. Functional Status was assessed by the Goldman Specific Activity Scale. RESULTS: UMI subjects had an increased prevalence of abnormal functional status compared to no MI controls (22% vs 11%, P < 0.05). This association was independent of sex, obesity, smoking, diabetes, and pulmonary disease. It became insignificant after stratifying for echocardiographic abnormalities. Compared to no MI controls, UMI subjects with impaired functional status had a higher mortality hazard ratio (HR 7.2; P<0.0001) than those without impaired functional status (HR 2.7; P = 0.02). In UMI subjects with impaired functional status and any echocardiographic abnormality signifying global ventricular dysfunction (systolic or diastolic dysfunction, left atrial or left ventricular enlargement), the mortality risk was even higher (HR 9.5; P<0.001) and persisted in multivariate analyses. This increased mortality risk was unaffected by adjustment for regional wall motion abnormalities. CONCLUSIONS: The assessment of impaired functional status and echocardiographic abnormalities improves the prognostic significance of UMI. Even in the absence of regional wall motion abnormalities, structural abnormalities of global dysfunction may play a role in mediating the increased mortality associated with UMI. PMID- 17286649 TI - Evaluation of effects of intra aortic balloon counterpulsation on autonomic nervous system functions by heart rate variability analysis. AB - BACKGROUND: In patients with acute myocardial infarction (AMI), intraaortic balloon counterpulsation (IABC) may improve cardiac performance, decrease the incidence of recurrent ischemia, and improve survival. Although there have been several reports concerning circulatory maintenance with the IABC, response of the autonomic nervous system to these hemodynamic changes is not clear. Heart rate variability (HRV) analysis has been extensively used to evaluate autonomic modulation of sinus node and to identify patients at risk for an increased cardiac mortality. In this study, we evaluated effects of the IABC on autonomic nervous system functions by HRV analysis. METHODS: The study group was composed of 32 consecutive patients (13 female, 19 male aged 61.8 +/- 8.8 years) undergoing IABC. Transthoracic echocardiography and 1-hour Holter recordings for HRV analysis in each IAB pumping mode were obtained. RESULTS: The IABC improved left ventricular diastolic and systolic functions as well as caused an increase in SDNN1, PNN50(1), RMSSD1, and HF1 and a decrease in LF1, LF/HF1, mean heart rate, and the number of ventricular extrasystoles. The improvements in HRV parameters were correlated with some hemodynamic changes such as the increase in MAP and CO during counterpulsation. The only independent factors affecting in hospital mortality were the change in LF/HF1 ratio (DeltaLF/HF1) and the change in the number of ventricular extrasystole (DeltaVES). The decrease in LF/HF1 > or = 4.9 decreased the mortality by 1.7-folds (RR = 0.6, P = 0.04, 95% CI: 0.1-2.3). The decrease in VES > or = 27/15 minutes resulted in mortality reduction by 16 folds (RR = 0.06, P = 0.02, 95% CI: 0.01-0.4). CONCLUSIONS: As a result, the IABC, especially in 1:1 support, causes an increase in HRV, decrease in sympathetic overactivity, and improvement in sympathovagal balance besides the favorable hemodynamic changes, and these electrophysiologic changes may explain the role of the IABC in the treatment of ventricular arrhythmias. PMID- 17286650 TI - QT dispersion significantly increases after implantable cardioverter defibrillator shocks. AB - OBJECTIVE: To determine whether QT dispersion (QTd), a noninvasive electrocardiographic parameter of ventricular tachyarrhythmia risk assessment, is changed by implantable cardioverter-defibrillator (ICD) shocks delivered during implantation process, to analyze the duration of these changes, and to further evaluate the effect of amiodarone on these parameters. METHODS: Twenty-six consecutive patients who are scheduled to undergo ICD implantation for aborted sudden cardiac death or documented symptomatic sustained ventricular tachycardia were enrolled into the study. A simultaneous 12-lead electrocardiogram (ECG) was recorded after the ICD implantation just before starting the testing shock when the patients were under general anesthesia (baseline record) and at 1st, 5th, 10th, 15th, 20th, 25th, and 30th minutes after the successful shocks. RR interval, QT interval, corrected QT interval (QTc), QTd, and corrected QTd (QTcd) were all measured and calculated on ECG. RESULTS: At 1st minute after the successful shock, an abrupt increase (from 67.0 +/- 13.8 ms to 94.8+/-21 ms, P < 0.0001) was observed in QTcd, which was followed by a gradual return to the preshock values at 20th minute. Analysis of patients with and without long-term oral amiodarone treatment showed that in amiodarone-pretreated patients QTcd returned to the baseline value earlier than in patients without amiodarone treatment (15 minutes vs 20 minutes, respectively). CONCLUSIONS: ICD shocks cause an increase in QTcd lasting for up to 20th minute, which may predominate in some important clinical problems like electrical storm. Amiodarone, with the desirable effect on QTcd, may reduce the proarrhythmic effects of ICD shocks. PMID- 17286651 TI - The relationship between heart rate variability and heart rate turbulence dynamics after primary coronary angioplasty. AB - BACKGROUND: The application of heart rate turbulence (HRT) analysis for risk assessment after pharmacologically treated myocardial infarction (MI) was described in 1999. The aim of the present study was to evaluate the dynamics of HRT changes in long-term observation after MI treated with primary coronary angioplasty (PTCA). Moreover, the usefulness was assessed of early postinfarction heart rate variability (HRV) analysis for predicting HRT dynamics. METHODS: The study group consisted of 96 patients with MI treated with primary PTCA. Holter monitoring with HRV and HRT analysis was performed 3 days after the procedure and 1 year later. RESULTS: Twelve months after primary PTCA, an improvement (Type I HRT dynamics) was noted in 51 patients, and the worsening of both the HRT parameters (Type II HRT dynamics) in 34 patients. Fourteen patients showed the worsening of only one HRT parameter (Type III HRT dynamics). The following HRV parameters recorded in early postinfarction Holter monitoring had a significant influence on the risk of Type II HRT dynamics: SDNN, RMSSD, Triangle Index and Delta LF/HF (mean day-time LF/HF - mean night-time LF/HF). Only the latter was found in the multivariate analysis as significantly connected with worsened HRT. During the follow-up, SDNN and Triangular Index improved in all the patients. CONCLUSIONS: HRT after myocardial infarction treated with primary PTCA presents a significant dynamics, which is different than dynamics of HRV. An abnormal circadian pattern of autonomic activity is a finding that helps identify patients who need to have HRT analysis repeated during a long-term follow-up, due to the tendency for HRT to change with time toward the prognostically unfavorable values. PMID- 17286652 TI - Significance of lead strength during exercise testing. AB - BACKGROUND: The aim of the study was to evaluate the contribution of relative lead strengths to exercise-induced ECG changes (ST depression) to predict the degree of myocardial ischemia as compared to the angiograms. This was accomplished by comparing the magnitude of ST depression to the ST/R ratio. Studies have shown that the diagnostic strength of a lead is directly related to the R wave amplitude and that sensitivity is significantly improved. METHODS: Three hundred patients, who underwent treadmill exercise testing and coronary angiography revealing significant coronary narrowing (> or = 70% luminal diameter narrowing), were studied, along with 150 patients clear of significant coronary artery disease (<70% luminar diameter narrowing). Our goal was to determine the correlation between the relative lead strengths, using a constructed ST/R ratio, to exercise induced ECG changes (ST depression) to predict the presence of myocardial ischemia as compared to angiographic findings. Using a cutoff of 0.1 for the ST/R ratio, our data were compared to the sensitivity and specificity of 1.0 mm ST depression. RESULTS: Overall sensitivity was improved for the ST/R ratio (84% vs 78%), while specificity was slightly decreased (81% vs 92%) in comparison to standard ST depression. When differentiating between R wave amplitudes, those with R wave < or = 10 mm showed significantly improved sensitivity (88% vs 54%) and a minor decrease in specificity (90% vs 92%). In those with R wave > or = 20 mm, the sensitivity of ST depression was higher (88% vs 71%) but the ST/R ratio was much more specific (88% vs 46%). No significant difference was observed when differentiating between male and female patients. CONCLUSION: We found that the correction of ST depression for R wave amplitude results in improved sensitivity in patients with low R waves and specificity in patients with very tall R waves (R > or = 20 mm). PMID- 17286653 TI - Slow delayed rectifier potassium current (IKs) and the repolarization reserve. AB - The aim of this review is to present the properties of the slow component of the delayed rectifier potassium current (IKs) in the human ventricle. The review gives a detailed description of the physiology, molecular biology and pharmacology of the IKs current, including kinetic properties, genetic structures, agonists and antagonists. The authors also present the role of the IKs current in the human cardiac repolarization focusing on several pathophysiological situations, such as the LQT syndrome and the Torsade de Pointes arrhythmia. PMID- 17286654 TI - Introductory Note to Alfred Nobel's Will. PMID- 17286655 TI - Alfred Nobel's Will. PMID- 17286656 TI - The ECG pattern of isolated right ventricular infarction during percutaneous coronary intervention. AB - Isolated right ventricular infarction (RVI) is a rare event. The electrocardiographic (ECG) pattern of RVI, ST-elevation in lead V4R and in anterior chest leads V1-3 is similar to that of a proximal occlusion of a small, nondominant right coronary artery (RCA). The ECG changes may be misinterpreted as signs of infarction of the anterior wall. This paper describes a case of isolated temporary occlusion of the major side branches of the RCA during percutaneous coronary intervention, recognized by angiography findings and typical ECG changes. This case demonstrates how one might avoid wrong decisions even in the catheterization laboratory by putting attention to the anatomical interpretation of the ECG. PMID- 17286657 TI - 'Not guilty' but not necessarily 'innocent': a clinician's guide to negative trial results in the veterinary literature. PMID- 17286658 TI - Vedaprofen therapy in cats with upper respiratory tract infection or following ovariohysterectomy. AB - OBJECTIVES: The antipyretic and analgesic efficacy of vedaprofen (at a dose of 0.5 mg/kg) was evaluated after repeated once-daily administration (for three or five days) to 80 cats with upper respiratory tract disease or 302 cats undergoing ovariohysterectomy. METHODS: Both clinical trials were randomised, double blinded and placebo controlled. RESULTS: In the upper respiratory tract disease trial, vedaprofen produced a significant reduction in rectal temperature when compared with cats administered antimicrobial treatment only. This antipyretic activity lasted at least four hours after administration on the first day of treatment (day 0) and at least eight hours on day 1 and day 2. Significantly more cats in the treatment group were classified as having returned to normal on day 5, day 6 and day 7 compared with the placebo group. In the ovariohysterectomy trial, scores for behaviour (on day 1, day 2 and day 3) and appetite (on day 1 and day 2) were significantly better in the vedaprofen group than in the placebo-treated cats. CLINICAL SIGNIFICANCE: Vedaprofen produced a clinically relevant reduction in body temperature and a more rapid return to normality in cats with upper respiratory tract disease. Vedaprofen treatment also resulted in more rapid recovery, presumably through the relief of pain and inflammation, in cats that had undergone soft tissue surgery. PMID- 17286659 TI - Sample size and statistical power in the small-animal analgesia literature. AB - OBJECTIVE: To document the power and required sample sizes to achieve certain treatment objectives in the veterinary analgesia literature. METHODS: Pubmed's MEDLINE database and selected journals were searched. Only publications produced between 1994 and 2004 that reported 'no difference' between experimental groups in the abstract, results or conclusion sections and those that were randomised, prospective and blinded were reviewed. The data reported in the publications were then subjected to power analyses to determine the power and necessary sample size (to achieve a power of 0.8) to allow detection of 20 per cent, 50 per cent and 80 per cent treatment effects. RESULTS: Twenty-two studies provided sufficient data for analysis. Five out of 22 (23 per cent) had sufficient power to detect a 20 per cent treatment effect, 12 of 22 (54 per cent) had sufficient power to detect a 50 per cent treatment effect and 18 of 22 (82 per cent) had sufficient power to detect an 80 per cent treatment effect. The mean number of animals required per group to document a 20 per cent, 50 per cent and 80 per cent treatment effect were 90, 15 and 7, respectively. CLINICAL SIGNIFICANCE: Publications that report no significant difference between analgesic regimens may have committed a Type II error. The reader may inappropriately conclude that there is no difference between treatments when there may, in fact, be a superior analgesic regimen. Clinical practice based on the principles of evidence-based medicine could therefore result in suboptimal care for patients. PMID- 17286660 TI - Transcatheter embolisation of patent ductus arteriosus using an Amplatzer vascular plug in six dogs. AB - OBJECTIVES: The objective of this study was to assess the feasibility of transcatheter embolisation of a patent ductus arteriosus using an Amplatzer vascular plug (Amplatzer Medical UK) in six dogs. METHODS: The Amplatzer vascular plug is a self-expandable, cylindrical device attached to a delivery cable. In all the dogs, the device was delivered transvenously. Successful device implantation was defined as firm anchorage of the device squarely within the distal part of the ductus arteriosus with no intra- or postoperative dislodgement. Successful occlusion of the ductus arteriosus occurred if a disappearance of the continuous murmur was achieved 24 hours after placement of the Amplatzer vascular plug. RESULTS: The age of the dogs ranged from 16 weeks to 7.5 years. Their weights ranged from 2.9 to 27.6 kg (median 6 kg). Two dogs had congestive heart failure before embolisation. Successful device implantation was achieved in all dogs. Successful occlusion of the ductus arteriosus was achieved in four of the six dogs. Complications included mild lameness, residual shunting, and bruising and pruritus around the surgical wound site. At follow-up, two dogs had a continuous murmur and one required treatment for congestive heart failure. CLINICAL SIGNIFICANCE: This technique may represent a clinically effective and less expensive alternative to the use of an Amplatzer duct occluder (Amplatzer Medical UK) in dogs with medium-sized patent ductus arteriosus. Further investigations are required to fully evaluate its efficacy and safety in various sizes and types of patent ductus arteriosus, and to determine the optimal device size in relation to the size of the ductus. PMID- 17286661 TI - Influence of surgical approach on the efficacy of the intervertebral disk fenestration: a cadaveric study. AB - OBJECTIVES: To investigate the influence of different approach angles on the amount of nucleus pulposus removed during intervertebral disc fenestration in dogs. METHODS: Twenty cadavers of beagle dogs were randomly divided into four groups: a control group and three treatment groups in which intervertebral fenestration was performed using either a dorsal, dorsolateral or lateral approach between the 12th thoracic and second lumbar spaces. The volume of nucleus pulposus, the weight of the residual nucleus pulposus and the angle of the working sector were measured. The ratio of the residual nucleus pulposus weight to the nucleus pulposus volume was used to evaluate the efficacy of the performed fenestration. Data were analysed with Kruskal-Wallis analysis of variance between groups on ranks with correction for ties and Bonferroni correction for multiple comparisons. Correlation between ratio and working angle was calculated using a Spearman's rank test (P<0.05). RESULTS: The calculated ratio of nuclear weight to volume was significantly less in the lateral approach group than that in the other groups. The working sector was widest in the dorsolateral approach group, but this did not correlate with efficient fenestration. CLINICAL SIGNIFICANCE: Using the lateral approach for intervertebral disc fenestration may increase the efficiency of the fenestration procedure. PMID- 17286662 TI - The anti-emetic efficacy of maropitant (Cerenia) in the treatment of ongoing emesis caused by a wide range of underlying clinical aetiologies in canine patients in Europe. AB - OBJECTIVES: The efficacy of maropitant (Cerenia; Pfizer Inc.) as an anti-emetic for use in dogs with ongoing emesis was evaluated in a two-phase multi-centric study conducted at veterinary clinics in France, Italy, Slovakia and the UK. METHODS: In phase I, dogs with ongoing emesis were randomised in a 1:1 ratio to either maropitant (32 dogs) or metoclopramide (34 dogs). In phase II, dogs were randomised in a 2:1 ratio to maropitant (77 dogs) or metoclopramide (40 dogs). Maropitant was administered subcutaneously at 1 mg/kg/day for up to five days. Metoclopramide was administered as recommended on the product labels as licensed at 0.5 to 1 mg/kg/day subcutaneously or orally with the daily dose divided over two to three administrations per day for up to three to five days. RESULTS: In phase I, 97 per cent of dogs treated with maropitant and 71 per cent of dogs treated with metoclopramide did not vomit after treatment (P<0.01). The mean number of emetic events after maropitant treatment was significantly reduced compared with that after metoclopramide treatment (P=0.01). In phase II, the occurrence of emesis was lower for maropitant during the first 24 hours (P<0.0001) and for each day thereafter. CLINICAL SIGNIFICANCE: A single daily dose of maropitant was more effective than metoclopramide administered two or three times daily in the treatment of emesis caused by various aetiologies in dogs. PMID- 17286663 TI - Hypertrophic osteopathy associated with infective endocarditis in an adult boxer dog. AB - A 20-month-old, entire male boxer dog was presented with lethargy and intermittent shifting limb lameness. Diagnostic tests revealed aortic valve vegetations suggestive of infective endocarditis causing severe aortic outflow obstruction, and hypertrophic osteopathy of all four limbs. The dog was treated symptomatically and euthanised four days later. The association of infective endocarditis and hypertrophic osteopathy has been poorly documented in the veterinary literature. The pathogenesis of hypertrophic osteopathy is unknown; however, four theories have been put forth to explain this disease: pulmonary shunting, vagal nerve stimulation, humoral substances produced by neoplastic cells and megakaryocyte/platelet clump hypothesis. PMID- 17286665 TI - Bilateral parieto-occipital dermoid sinuses in a Rottweiler. AB - Bilateral dermoid sinuses were identified on the parieto-occipital region of a Rottweiler. Diagnosis was confirmed by histological examination after successful complete surgical resection. The dermoid sinuses were independent with separate tracts. This unusual parasagittal location can be explained by craniofacial development: dermoid sinuses on the head could occur along the lines of embryological fusion and not only in the sagittal plane. A hypothesis of an origin at the level of the suture between the parietal and interparietal bones is possible in this case. PMID- 17286664 TI - Treatment of a case of refractory feline chronic gingivostomatitis with feline recombinant interferon omega. AB - Chronic gingivostomatitis is a common debilitating disease in cats, which is often refractory to medical and surgical treatment. An eight-year-old, neutered female domestic shorthair cat with a history of gingivitis was presented with chronic gingivostomatitis. Initial treatment by extraction of all premolars and molars was unsuccessful. However, the condition resolved within six weeks of treatment with feline recombinant interferon omega (Virbagen; Virbac). PMID- 17286666 TI - Successful closure of feline axillary wounds by reconstruction of the elbow skin fold. AB - This report describes the successful closure of five chronic feline axillary wounds. The aetiology was known to be forelimb entrapment in a neck collar in three cases and was suspected in the others. Each cat underwent a single surgical procedure during which the wound was debrided, the normal structure of the elbow skin fold was restored and the remaining skin defect was closed primarily. None of the cats had undergone any previous reconstruction attempts. No postoperative complications were observed and the wounds healed uneventfully. Cats have well developed elbow skin folds, allowing a wide range of limb motion to occur. Having a forelimb trapped in a neck collar not only creates a wound in the axilla but also disrupts the normal anatomy of the skin fold. This report demonstrates that restoring the elbow skin fold before closing the wound may improve the chances of a successful reconstruction at the first surgical intervention. PMID- 17286667 TI - Extradural spinal juxtafacet (synovial) cysts in three dogs. AB - Three dogs were presented for investigation of spinal disease and were diagnosed with extradural spinal juxtafacet cysts of synovial origin. Two dogs that were presented with clinical signs consistent with pain in the lumbosacral region associated with bilateral hindlimb paresis were diagnosed using magnetic resonance imaging. Both cysts were solitary and associated with the L6-7 dorsal articulations; both the dogs had a transitional vertebra in the lumbosacral region. A third dog that was presented with progressive paraparesis localised to T3-L3 spinal cord segments and compression of the spinal cord at T13-L1 was diagnosed using myelography. A solitary multiloculated cyst was found at surgery. Decompressive surgery resulted in resolution of the clinical signs in all three dogs. Immunohistological findings indicated that one to two layers of vimentin positive cells consistent with synovial origin lined the cysts. PMID- 17286668 TI - What is your diagnosis? Paracetamol poisoning. PMID- 17286671 TI - Home-based palliative care in Sydney, Australia: the carer's perspective on the provision of informal care. AB - The provision of home-based palliative care requires a substantial unpaid contribution from family and friends (i.e. informal care). The present cross sectional descriptive study, conducted between September 2003 and April 2004, describes this contribution and the impact it has on those providing informal care. The participants were 82 informal carers of patients registered with two community palliative care services in Sydney, Australia (40% of eligible carers). Carers were interviewed to assess the care recipient's care needs, the care provided by the informal carer and the health status of the carer (using the 36 Item Short Form Health Survey). A number of open-ended questions asked about the impact of providing care and the type of support that carers would find helpful. Most carers reported that care recipients required help with household tasks and many needed assistance with personal activities of daily living, taking medications and organisational tasks. In the majority of cases, the principal carer provided all or most of this help. Although, on average, the physical health of carers was similar to that of the Australian population, their mental health scores were lower. Many carers reported effects on social and family relationships, restrictions on their participation in work and leisure activities, and a range of emotional reactions to their caring situation. The support carers said they would like included information and advice, in-home respite, help with household tasks, and financial support. The present study supports the view that effective support for carers must recognise the pre existing relationship between carer and recipient, and the differing needs of individual carers. PMID- 17286672 TI - Can a publicly funded home care system successfully allocate service based on perceived need rather than socioeconomic status? A Canadian experience. AB - The present quantitative study evaluates the degree to which socioeconomic status (SES), as opposed to perceived need, determines utilisation of publicly funded home care in Ontario, Canada. The Registered Persons Data Base of the Ontario Health Insurance Plan was used to identify the age, sex and place of residence for all Ontarians who had coverage for the complete calendar year 1998. Utilisation was characterised in two dimensions: (1) propensity - the probability that an individual received service, which was estimated using a multinomial logit equation; and (2) intensity - the amount of service received, conditional on receipt. Short- and long-term service intensity were modelled separately using ordinary least squares regression. Age, sex and co-morbidity were the best predictors (P < 0.0001) of whether or not an individual received publicly funded home care as well as how much care was received, with sicker individuals having increased utilisation. The propensity and intensity of service receipt increased with lower SES (P < 0.0001), and decreased with the proportion of recent immigrants in the region (P < 0.0001), after controlling for age, sex and co morbidity. Although the allocation of publicly funded home care service was primarily based on perceived need rather than ability to pay, barriers to utilisation for those from areas with a high proportion of recent immigrants were identified. Future research is needed to assess whether the current mix and level of publicly funded resources are indeed sufficient to offset the added costs associated with the provision of high-quality home care. PMID- 17286673 TI - A health inequalities perspective on violence against women. AB - The present paper argues that the physical and mental health consequences of gender-based violence constitute a major public health problem in the UK and a source of significant health inequality. The concept of violence against women is explored alongside brief examples of the mental and physical health impact of this violence. While the impact on women's health is relatively uncontested, the extent to which social divisions such as poverty, class and minority ethnic status create specific vulnerabilities to violence are more controversial. A widely held view within the movement to support survivors within the UK has been that violence against women cuts across class and ethnicity, and is found in all communities and classes. A more nuanced discussion of the way in which poverty and ethnic background may create particular vulnerabilities is explored. Disentangling cause and consequence, and also the barriers to help-seeking for minority ethnic women are discussed. The role of social workers in addressing the way in which violence against women is both ubiquitous but marginal in their caseloads is discussed, and appropriate interventions to respond to health inequality issues are proposed. PMID- 17286674 TI - Employment support agencies in the UK: current operation and future development needs. AB - Disabled people are amongst the most excluded in society, while people with learning disability have the lowest rates of employment. Supported employment promises to address the gaps, but it is a new approach, one whose development has been incremental. The present authors explore some of the features of agencies providing employment support to disabled people, together with their managers' views. This paper describes semistructured telephone interviews with the managers of 31 employment support agencies. The survey sought to understand the types of service provided, the staff and caseload numbers, the training offered, and the targets used. The authors also asked the managers what would help them in delivering employment opportunities to disabled people. The responses of the managers highlight gaps between current policy and practice. Particular attention is given to the use of targets, fragmented funding and what managers consider is required to improve employment opportunities for disabled people. Managers endorsed the vision expressed in current policy, and identified numerous obstacles to its implementation in employment support. Taken together, their views can be used to guide the development of supported employment. PMID- 17286675 TI - Assessing the Registered Nursing Care Contribution for older people in care homes: issues of reliability and validity. AB - The present paper reports on a study designed to investigate the validity and reliability of the Registered Nursing Care Contribution (RNCC) tool for assessing the level of nursing care required by care home residents. Care plan data from 186 residents in participating care homes were assessed by multiple assessors using the RNCC tool (i.e. care home registered nurses, a nurse researcher, an external care home expert and a nurses consultant). The Minimum Data Set (MDS) rating was used as a validated comparison. The findings from the study indicated that there were disparities between the RNCC and MDS bandings, and between different raters, with the external care home expert achieving the closest agreement with the MDS. This suggests that the use of the RNCC tool varies considerably according to the assessor, which also suggests that training of users is needed to ensure consistency and reliability. However, the difference between the outcomes of using the RNCC tool and the MDS suggests that assessment of nursing need may need to be re-examined to ensure validity. PMID- 17286676 TI - The organisation, form and function of intermediate care services and systems in England: results from a national survey. AB - This paper reports the results of a postal survey of intermediate care coordinators (ICCs) on the organisation and delivery of intermediate care services for older people in England, conducted between November 2003 and May 2004. Questionnaires, which covered a range of issues with a variety of quantitative, tick-box and open-ended questions, were returned by 106 respondents, representing just over 35% of primary care trusts (PCTs). The authors discuss the role of ICCs, the integration of local systems of intermediate care provision, and the form, function and model of delivery of services described by respondents. Using descriptive and statistical analysis of the responses, they highlight in particular the relationship between provision of admission avoidance and supported discharge, the availability of 24-hour care, and the locations in which care is provided, and relate their findings to the emerging evidence base for intermediate care, guidance on implementation from central government, and debate in the literature. Whilst the expansion and integration of intermediate care appear to be continuing apace, much provision seems concentrated in supported discharge services rather than acute admission avoidance, and particularly in residential forms of post-acute intermediate care. Supported discharge services tend to be found in residential settings, while admission avoidance provision tends to be non-residential in nature. Twenty-four hour care in non-residential settings is not available in several responding PCTs. These findings raise questions about the relationship between the implementation of intermediate care, and the evidence for and aims of the policy as part of National Health Service modernisation, and the extent to which intermediate care represents a genuinely novel approach to the care and rehabilitation of older people. PMID- 17286677 TI - Networks and governance: the case of intermediate care. AB - The present paper describes a novel approach to the study of services conceptualised as networks. It uses data collected as part of a case study evaluation of intermediate care, a 'joined-up government' policy that was explicitly intended to dissolve the boundaries between health and social care services. The evaluation was undertaken in five localities in England. Routine service use data were collated and standardised for the 12-month period from November 2002 to October 2003. A cohort of 258 service users was recruited during a census month (June 2003), and more detailed data on their personal characteristics and experiences prior to and during their intermediate care episode were collected. Information was obtained for 153 of these people, covering their experience during the 6 months following discharge. A graphical method of depicting individuals' movements between services was devised and a number of measures were used to investigate the network-like features of the data. User outcomes were explored by examining the relationship of characteristics of service users to their location at 6 months after discharge. The results of the analyses show that the five sites were developing service configurations that facilitated transitions between health, social care and other services, and that individual needs were taken into account in the decisions made about which people transferred into which services. While the results cannot be said to show that joined-up government works, they are consistent with the argument that joined-up government goes beyond partnership-type concepts, and in practice, involves the creation of what might be termed integrated service networks. PMID- 17286678 TI - Choice in the context of informal care-giving. AB - Extending choice and control for social care service users is a central feature of current English policies. However, these have comparatively little to say about choice in relation to the informal carers of relatives, friends or older people who are disabled or sick. To explore the realities of choice as experienced by carers, the present paper reviews research published in English since 1985 about three situations in which carers are likely to face choices: receiving social services; the entry of an older person to long-term care; and combining paid work and care. Thirteen electronic databases were searched, covering both the health and social care fields. Databases included: ASSIA; IBSS; Social Care Online; ISI Web of Knowledge; Medline; HMIC; Sociological Abstracts; INGENTA; ZETOC; and the National Research Register. The search strategy combined terms that: (1) identified individuals with care-giving responsibilities; (2) identified people receiving help and support; and (3) described the process of interest (e.g. choice, decision-making and self-determination). The search identified comparatively few relevant studies, and so was supplemented by the findings from another recent review of empirical research on carers' choices about combining work and care. The research evidence suggests that carers' choices are shaped by two sets of factors: one relates to the nature of the care giving relationship; and the second consists of wider organisational factors. A number of reasons may explain the invisibility of choice for carers in current policy proposals for increasing choice. In particular, it is suggested that underpinning conceptual models of the relationship between carers and formal service providers shape the extent to which carers can be offered choice and control on similar terms to service users. In particular, the exercise of choice by carers is likely to be highly problematic if it involves relinquishing some unpaid care-giving activities. PMID- 17286690 TI - Stereological estimation of surface area and barrier thickness of fish gills in vertical sections. AB - Previous morphometric methods for estimation of the volume of components, surface area and thickness of the diffusion barrier in fish gills have taken advantage of the highly ordered structure of these organs for sampling and surface area estimations, whereas the thickness of the diffusion barrier has been measured orthogonally on perpendicularly sectioned material at subjectively selected sites. Although intuitively logical, these procedures do not have a demonstrated mathematical basis, do not involve random sampling and measurement techniques, and are not applicable to the gills of all fish. The present stereological methods apply the principles of surface area estimation in vertical uniform random sections to the gills of the Brazilian teleost Arapaima gigas. The tissue was taken from the entire gill apparatus of the right-hand or left-hand side (selected at random) of the fish by systematic random sampling and embedded in glycol methacrylate for light microscopy. Arches from the other side were embedded in Epoxy resin. Reference volume was estimated by the Cavalieri method in the same vertical sections that were used for surface density and volume density measurements. The harmonic mean barrier thickness of the water-blood diffusion barrier was calculated from measurements taken along randomly selected orientation lines that were sine-weighted relative to the vertical axis. The values thus obtained for the anatomical diffusion factor (surface area divided by barrier thickness) compare favourably with those obtained for other sluggish fish using existing methods. PMID- 17286691 TI - Identification of the three-dimensional gel microstructure from transmission electron micrographs. AB - Mass transport in gels depends crucially on local properties of the gel network. We propose a method for identifying the three-dimensional (3D) gel microstructure from statistical information in transmission electron micrographs. The gel strand network is modelled as a random graph with nodes and edges (branches). The distribution of edge length, the number of edges at nodes and the angles between edges at a node are estimated from transmission electron micrographs by image analysis methods. The 3D network is simulated by Markov chain Monte Carlo, with a probability function based on the statistical information found from the micrographs. The micrographs are projections of stained gel strands in slices, and we derive a formula for estimating the thickness of the stained gel slice based on the total projected gel strand length and the number of times that gel strands enter or exit the slice. PMID- 17286692 TI - Geometric approach to segmentation and protein localization in cell culture assays. AB - Cell-based fluorescence imaging assays are heterogeneous and require the collection of a large number of images for detailed quantitative analysis. Complexities arise as a result of variation in spatial nonuniformity, shape, overlapping compartments and scale (size). A new technique and methodology has been developed and tested for delineating subcellular morphology and partitioning overlapping compartments at multiple scales. This system is packaged as an integrated software platform for quantifying images that are obtained through fluorescence microscopy. Proposed methods are model based, leveraging geometric shape properties of subcellular compartments and corresponding protein localization. From the morphological perspective, convexity constraint is imposed to delineate and partition nuclear compartments. From the protein localization perspective, radial symmetry is imposed to localize punctate protein events at submicron resolution. Convexity constraint is imposed against boundary information, which are extracted through a combination of zero-crossing and gradient operator. If the convexity constraint fails for the boundary then positive curvature maxima are localized along the contour and the entire blob is partitioned into disjointed convex objects representing individual nuclear compartment, by enforcing geometric constraints. Nuclear compartments provide the context for protein localization, which may be diffuse or punctate. Punctate signal are localized through iterative voting and radial symmetries for improved reliability and robustness. The technique has been tested against 196 images that were generated to study centrosome abnormalities. Corresponding computed representations are compared against manual counts for validation. PMID- 17286693 TI - Grey-scale conversion X-ray mapping by EDS of multielement and multiphase layered microstructures. AB - A procedure for grey-scale conversion of energy dispersive spectroscopy X-ray maps has been developed, which is particularly useful for the plotting of line composition profiles across modified layered engineering surfaces. The method involves (a) the collection of grey-scale elemental maps, (b) the calculation of mean grey-scale levels along strips parallel to the layered microstructure and (c) the conversion of grey-scale line profiles into composition line profiles. As an example of the grey-scale conversion method and its advantages for multielement and multiphase layered microstructures, the procedure has been applied to a layered microstructure that results from a plasma-sprayed metallic MCrAlY coating onto a nickel-superalloy turbine blade. As a further demonstration of the accuracy and amount of compositional data that can be obtained with this procedure, measured compositional profiles have been obtained for several long term isothermal heat treatments in which significant interdiffusion has taken place. The resulting composition profiles have greatly improved counting statistics compared to traditional point-by-point scans for the same scanning electron microscope time and may be considered as a rapid alternative to energy dispersive spectroscopy spectrum imaging. The composition profiles obtained may be conveniently compared with results of multicomponent thermodynamic modelling of interdiffusion. PMID- 17286694 TI - Fluctuation X-ray microscopy: a novel approach for the structural study of disordered materials. AB - Measuring medium-range order is a challenging and important problem in the structural study of disordered materials. We have developed a new technique, fluctuation x-ray microscopy, that offers quantitative insight into medium-range correlations in disordered materials at nanometre and larger length scales. In this technique, which requires a spatially coherent x-ray beam, a series of speckle patterns are measured at a large number of locations in a sample using various illumination sizes. Examination of the speckle variance as a function of the illumination spot size allows the structural correlation length to be measured. To demonstrate this technique we have studied polystyrene latex spheres, which serve as a model for a dense random-packed glass, and for the first time have measured the correlation length in a disordered system by fluctuation X-ray microscopy. We discuss data analysis and procedures to correct for shot noise and detector noise. This approach could be used to explore medium range order and subtle spatial structural changes in a wide range of disordered materials, from soft matter to nanowire arrays, semiconductor quantum dot arrays and magnetic materials. PMID- 17286695 TI - Fluorescence relaxation in 3D from diffraction-limited sources of PAGFP or sinks of EGFP created by multiphoton photoconversion. AB - The relaxation of fluorescence from diffraction-limited sources of photoactivatable green fluorescent protein (PAGFP) or sinks of photobleached enhanced GFP (EGFP) created by multiphoton photo-conversion was measured in solutions of varied viscosity (eta), and in live, spherical Chinese hamster ovary (CHO) cells. Fluorescence relaxation was monitored with the probing laser fixed, or rapidly scanning along a line bisected by the photoconversion site. Novel solutions to several problems that hamper the study of PAGFP diffusion after multiphoton photoconversion are presented. A theoretical model of 3D diffusion in a sphere from a source in the shape of the measured multiphoton point-spread function was applied to the fluorescence data to estimate the apparent diffusion coefficient, D(ap). The model incorporates two novel features that make it of broad utility. First, the model includes the no-flux boundary condition imposed by cell plasma membranes, allowing assessment of potential impact of this boundary on estimates of D(ap). Second, the model uses an inhomogeneous source term that, for the first time, allows analysis of diffusion from sources produced by multiphoton photoconversion pulses of varying duration. For diffusion in aqueous solution, indistinguishable linear relationships between D(ap) and eta( 1) were obtained for the two proteins: for PAGFP, D(aq)= 89 +/- 2.4 microm2 s(-1) (mean +/- 95% confidence interval), and for EGFP D(aq)= 91 +/- 1.8 microm2 s(-1). In CHO cells, the application of the model yielded D(ap)= 20 +/- 3 microm2 s(-1) (PAGFP) and 19 +/- 2 microm2 s(-1) (EGFP). Furthermore, the model quantitatively predicted the decline in baseline fluorescence that accompanied repeated photobleaching cycles in CHO cells expressing EGFP, supporting the hypothesis of fluorophore depletion as an alternative to the oft invoked 'bound fraction' explanation of the deviation of the terminal fluorescence recovery from its pre bleach baseline level. Nonetheless for their identical diffusive properties, advantages of PAGFP over EGFP were found, including an intrinsically higher signal/noise ratio with 488-nm excitation, and the requirement for approximately 1/200th the cumulative light energy to produce data of comparable signal/noise. PMID- 17286696 TI - Direct probing of solvent-induced charge degradation in polypropylene electret fibres via electrostatic force microscopy. AB - Electrostatic force microscopy was used to directly probe solvent-induced charge degradation in electret filter media. Electrostatic force gradient images of individual polypropylene electret fibres were used to quantify the extent of charge degradation caused by the immersion of the fibres into isopropanol. Electrostatic force gradient images were obtained by monitoring the shifts in phase and frequency between the oscillations of the biased atomic force microscopy (AFM) cantilever and those of the piezoelectric driver. Electrostatic force microscopy measurements were performed using non-contact scans at a constant tip-sample separation of 75 nm with varied bias voltages applied to the cantilever. Mathematical expressions, based on the capacitance of the tip-sample system, were used to model the phase and frequency shifts as functions of the applied bias voltage to the tip and the offset voltage due to the fibre's charge. Quantitative agreement between the experimental data and the simplified model was observed. PMID- 17286697 TI - Size-selective colloidal-gold localization in transmission X-ray microscopy. AB - Colloidal gold is a useful marker for functional-imaging experiments in transmission X-ray microscopy. Due to the low contrast of gold particles with small diameters it is necessary to develop a powerful algorithm to localize the single gold particles. The presented image-analysis algorithm for identifying colloidal gold particles is based on the combination of a threshold with respect to the local absorption and shape discrimination, realized by fitting a Gaussian profile to the identified regions of interest. The shape discrimination provides the possibility of size-selective identification and localization of single colloidal gold particles down to a diameter of 50 nm. The image-analysis algorithm, therefore, has potential for localization studies of several proteins simultaneously and for localization of fiducial markers in X-ray tomography. PMID- 17286698 TI - Characterization of uniform ultrathin layer for z-response measurements in three dimensional section fluorescence microscopy. AB - Layer-by-layer technique is used to adsorb a uniform ultrathin layer of fluorescently labelled polyelectrolytes on a glass cover slip. Due to their thickness, uniformity and fluorescence properties, these ultrathin layers may serve as a simple and applicable standard to directly measure the z-response of different scanning optical microscopes. In this work we use ultrathin layers to measure the z-response of confocal, two-photon excitation and 4Pi laser scanning microscopes. Moreover, due to their uniformity over a wide region, i.e. cover slip surface, it is possible to quantify the z-response of the system over a full field of view area. This property, coupled with a bright fluorescence signal, enables the use of polyelectrolyte layers for representation on sectioned imaging property charts: a very powerful method to characterize image formation properties and capabilities (z-response, off-axis aberration, spherical aberration, etc.) of a three-dimensional scanning system. The sectioned imaging property charts method needs a through-focus dataset taken from such ultrathin layers. Using a comparatively low illumination no significant bleaching occurs during the excitation process, so it is possible to achieve long-term monitoring of the z-response of the system. All the above mentioned properties make such ultrathin layers a suitable candidate for calibration and a powerful tool for real-time evaluation of the optical sectioning capabilities of different three dimensional scanning systems especially when coupled to sectioned imaging property charts. PMID- 17286699 TI - A simple technique of image analysis for specific nuclear immunolocalization of proteins. AB - Colocalization of fluorescent signals in confocal microscopy is usually evaluated by inspecting merged images from different colour channels or by using commercially available software packages. We describe in this paper a simple method for assessment of nuclear localization of proteins in tissue sections through confocal immunolocalization, propidium iodide counterstaining and image analysis. Through a macro command developed for the public domain, Java-based software imagej, red, green, blue (RGB) images are automatically split in the red and green channels and a new image composed of the nonblack pixels coincident in both channels is created and inverted for better visualization. This method renders images devoid of both, extranuclear staining and background, thus emphasizing the nuclear signal. The resulting images can easily be used for comparison or quantification of the results. Given the simplicity of the technique and the worldwide diffusion of the software utilized, we think that this method could be useful in order to define standards of colocalization in confocal microscopy. PMID- 17286700 TI - Saccharomyces cerevisiae samples stained with FUN-1 dye can be stored at -20 degrees C for later observation. AB - FUN-1, a fluorescent vital dye, has been observed to form cylindrical intravacuolar structures within the vacuoles of metabolically active yeast cells. FUN-1 staining, which begins as a diffuse pool of fluorescent cytoplasmic stain, uses an unknown endogenous biochemical processing mechanism to compact and form orange-red cylindrical intravacuolar structures within the cell vacuole. In the clinical setting, FUN-1 is primarily used for identification of fungal infection. FUN-1 is utilized in the laboratory to distinguish between metabolically active and dead fungal cells. Although this stain is useful for distinguishing between live and dead fungal dead cells, few studies have utilized this chemical. This lack of use in the scientific community may be due to the requirement that cells are visualized directly after staining. Thus, it would be of interest to be able to stain cells and store them for later use. Our lab examined the longevity of cylindrical intravacuolar structures in two strains of Saccharomyces cerevisiae stained with FUN-1 and stored at -20 degrees C. We found that cylindrical intravacuolar structures could be reliably observed and imaged utilizing differential interference contrast microscopy and fluorescence microscopy for 21 days. We also observed that cells stained with FUN-1 would resume propagation on yeast extract, peptone, dextrose (YPD) plates after being frozen at -20 degrees C for 21 days. These modifications to the published procedure for FUN-1 dye staining should allow for a more prevalent and less time sensitive use of this important biological tool. PMID- 17286701 TI - Comments on the paper 'A novel 3D wavelet-based filter for visualizing features in noisy biological data', by Moss et al. AB - Moss et al. (2005) describe, in a recent paper, a filter that they use to detect lines. We noticed that the wavelet on which this filter is based is a difference of uniform filters. This filter is an approximation to the second-derivative operator, which is commonly implemented as the Laplace of Gaussian (or Marr Hildreth) operator. We have compared Moss' filter with (1) the Laplace of Gaussian operator, (2) an approximation of the Laplace of Gaussian using uniform filters and (3) a few common noise reduction filters. The Laplace-like operators detect lines by suppressing image features both larger and smaller than the filter size. The noise reduction filters only suppress image features smaller than the filter size. By estimating the signal-to-noise ratio and mean square difference of the filtered results, we found that the filter proposed by Moss et al. does not outperform the Laplace of Gaussian operator. We also found that for images with extreme noise content, line detection filters perform better than the noise reduction filters when trying to enhance line structures. In less extreme cases of noise, the standard noise reduction filters perform significantly better than both the Laplace of Gaussian and Moss' filter. PMID- 17286703 TI - Gender, pregnancy and the uptake of antenatal care services in Pakistan. AB - An integrated analysis of detailed ethnography and large-scale survey data is presented to explore the gendered influences on women's uptake of antenatal care (ANC) services in Punjab, Pakistan. Pregnancy and its associated decisions were shown to be normatively the older women's domain, with pregnant women and their husbands being distanced from the decision-making process. Women who successfully claimed ANC did so not by overtly challenging the dominant construction of young femininity, but rather by using existing gendered structures and channels of communication to influence authority figures. The quality of a woman's inter personal ties, particularly with her mother-in-law and husband, were found to be important in accessing resources, including ANC. Gendered influences were moderated by social class. Family finances were an important determinant of ANC use, as was women's education. Wealthier, higher status women also found it easier to circumvent gendered proscriptions against their mobility while pregnant. As well as illuminating the ways in which the sociocultural construction of gender acts to constrain women's access to ANC, the empirical findings are used to highlight significant inadequacies in the 'autonomy paradigm' that has dominated much of the research into women's reproductive health in South Asia. PMID- 17286704 TI - Chronic illness, expert patients and care transition. AB - During the last century demographic and epidemiological transitions have had a radical impact upon health and health service provision. A considerable body of research on the sociological aspects of living with chronic illness has accumulated. Debate has focused on how social environments shape disability related experiences, and the extent to which individual responses define health outcomes. Through the establishment of the Expert Patients Programme (EPP) in 2001, the Department of Health has sought to enhance NHS patients' self management capacities. This paper discusses three areas relevant to this: the policy formation process leading up to the EPP's present stage of development; the evidence base supporting claims made for its effectiveness; and the significance of psychological concepts such as self-efficacy in approaches to improving public health. The conclusion discusses NHS developments in primary care and public involvement in health and healthcare, and the implications that initiatives such as the EPP carry for the future. It is argued that to facilitate a constructive process of 'care transition' in response to epidemiological and allied change, awareness of cognitive/psychological factors involved in illness behaviours should not draw attention away from the social determinants and contexts of health. PMID- 17286705 TI - Avian flu: the creation of expectations in the interplay between science and the media. AB - This paper examines the emerging cultural patterns and interpretative repertoires in reports of an impending pandemic of avian flu in the UK mass media and scientific journals at the beginning of 2005, paying particular attention to metaphors, pragmatic markers ('risk signals'), symbolic dates and scare statistics used by scientists and the media to create expectations and elicit actions. This study complements other work on the metaphorical framing of infectious disease, such as foot and mouth disease and SARS, tries to link it to developments in the sociology of expectations and applies insights from pragmatics both to the sociology of metaphor and the sociology of expectations. PMID- 17286706 TI - The linear medical model of disability: mothers of disabled babies resist with counter-narratives. AB - This paper draws on the narratives of parents of disabled babies in order to conceptualise notions of enabling care. This analysis emerges from the Sheffield site of an ESRC research project Parents, Professionals and Disabled Babies: Identifying Enabling Care, which brings together the Universities of Sheffield and Newcastle-upon-Tyne. The linear heroic narrative is a dominant theme within Western culture. It is competitive and individualistic and tends to be future orientated in that actions conducted in the present are evaluated according to later outcomes. This linear narrative places much store on modernist interventions such as medicine, and tends to uphold professional boundaries and hierarchies. In the lifeworlds of parents, usually mothers, of disabled babies, this narrative can reinforce disempowering interpretations of disability and impairment. On the basis of 25 in-depth interviews, accompanying stories and ethnographic data, this paper suggests that parents are developing counter narratives which, at times, resist linear life models and free parents to enjoy their children as they are. If life is perceived as an open book rather than as a concluding chapter, parents are able to develop stories that are neither linear nor heroic but present and becoming. PMID- 17286707 TI - 'A politics of what': the enactment of peritoneal dialysis in indigenous Australians. AB - This paper explores, on the one hand, the requirements of the technologies and practices that have been developed for a particular type of renal patient and health network in Australia. On the other, we examine the cultural and practical specificities entailed in the performance of these technologies and practices in the Indigenous Australian context. The praxiographic orientation of the actor network approach - which has been called 'the politics of what' (Mol 2002) - enabled us to understand the difficulties involved in translating renal healthcare networks across cultural contexts in Australia; to understand the dynamic and contested nature of these networks; and to suggest possible strategies that make use of the tensions between these two disparate networks in ways that might ensure better healthcare for Indigenous renal patients. PMID- 17286708 TI - Public health and the cult of humanity: a neglected Durkheimian concept. AB - Public health researchers have used a number of concepts derived from the work of Durkheim, such as anomie and social capital. One concept that has not been deployed in public health discourses is that of the cult of humanity - Durkheim's religion in a society organised around organic solidarity. This paper discusses Durkheim's views on religion and science, and the cult of humanity. The cult of humanity is characterised as having humanity at the centre of worship and combining elements of religion and science. Medicine and complementary therapies are identified as possible candidates to fulfil the role of the cult of humanity, but the institution of public health seems to be a particularly apt candidate. The paper concludes by discussing the way in which this analysis provides insight into the dual advocacy and academic functions of public health, the tension between individual choice and constraint and the buffering role of public health in relation to other social institutions. PMID- 17286709 TI - Unhealthy prisons: exploring structural determinants of prison health. AB - Prisoner health is influenced as much by structural determinants (institutional, environmental, political, economic and social) as it is by physical and mental constitutions of prisoners themselves. Prison health may therefore be better understood with greater insight into how people respond to imprisonment - the psychological pressures of incarceration, the social world of prison, being dislocated from society, and the impact of the institution itself with its regime and architecture. As agencies of disempowerment and deprivation, prisons epitomise the antithesis of a healthy setting. The World Health Organisation's notion of a 'healthy prison' is in this sense an oxymoron, yet the UK government has signalled that it is committed to WHO's core health promotion principles as a route to reducing health inequalities. This paper reports on the findings of an ethnographic study which was conducted in an adult male training prison in England, using participant observation, group interviewing, and one-to-one semi structured interviews with prisoners and prison officers. The paper explores how different layers of prison life impact on the health of prisoners, arguing that health inequalities are enmeshed within the workings of the prison system itself. PMID- 17286710 TI - Diets and discipline: the narratives of practice of university students with type 1 diabetes. AB - Type 1 diabetes is one of the most common chronic conditions of adolescence and young adulthood. It is characterised by a demanding and complex management regime. Individuals with diabetes must engage in continual self-care actions such as eating healthily and exercising if they are to minimise their risks of developing long-term diabetes' complications. Research has demonstrated, however, that many young adults experience difficulties with exercising and eating healthily. Narrative approaches could provide important insights into the reasons why young people do or do not experience difficulties here. In this article I examine the food consumption and exercise narratives of a particular group of young adults with type 1 diabetes, university students, to see what personal, social and cultural factors influence their practices. PMID- 17286717 TI - Evaluating psychodiagnostic decisions. AB - RATIONALE: Several frameworks can be used to evaluate decision making. These may relate to different aspects of the decision-making process, or concern the decision outcome. Evaluations of psychodiagnostic decisions have shown diagnosticians to be poor decision makers. In this essay we argue that this finding results from the evaluation of only one part of the diagnostic process. METHOD: We put forward that evaluations are typically carried out by comparing clinicians' behaviour to one of several normative models, for example hypothetico deductive reasoning. These models make strong assumptions about human reasoning capabilities, which make it almost impossible for people to measure up to them. The subsequent two parts of the psychodiagnostic process (causal explanation and treatment decisions), are typically not included in these evaluation studies. Treatment decisions are evaluated in effectiveness studies; that is, they are evaluated in terms of their outcomes, not in terms of the diagnosticians' decision processes. Psychodiagnosticians' causal explanation has hardly ever been the subject of evaluation. We argue that in order to achieve clinical excellence, this part of the psychodiagnostic process should also be well understood. RESULTS AND CONCLUSIONS: In this essay we first describe evaluation of psychodiagnostic decision making. We then propose a framework to describe causal explanation, that is, a situation assessment in terms of a causal schema or a story or script. We identify and discuss the tools available for evaluating this part of the psychodiagnostic process. PMID- 17286716 TI - An analysis of the evidence-practice continuum: is surgery for obstructive sleep apnoea contraindicated? AB - RATIONALE, AIMS AND OBJECTIVES: Currently there are multiple surgical interventions utilized in the treatment of adult obstructive sleep apnoea (OSA). The role of these operations remains controversial, with perspectives on treatment efficacy varying considerably. Despite this, their use is proliferating. OBJECTIVES: In this paper, we present the degree of variability that occurs in the application of these procedures, and examine the effectiveness of surgical intervention as a treatment for OSA. METHOD: A multi-centre retrospective clinical audit of consecutive, unselected surgical cases presenting at the sleep disorder clinics of two teaching hospitals in a major Australian city. Patients acted as their own historical controls, undergoing polysomnography pre and post surgery to gauge effectiveness. RESULTS: On variability demonstrate 94 individuals in this cohort received 220 individual upper airway surgical procedures, 184 occurred in their first operation (mean 2.5 per person; range 1 7) and 36 occurred in a second operation (n=18; cumulative mean of 4 per person; range 3-7). These 94 individuals received 41 varying combinations of surgery. Results on effectiveness demonstrate an overall physiological success rate of 13% (87% fail). One operation reduced OSA severity by 20% (patients still had severe OSA), and two operations by 35% (still moderate OSA). In contrast, conventional Continuous Positive Airway Pressure therapy controlled OSA (n=64). CONCLUSIONS: This case study demonstrates substantial procedural variability and limited effectiveness. This raises questions as to the quality of care, the treatment derived health outcomes of this population and of efficient resource allocation. This issue requires greater policy attention. PMID- 17286718 TI - Does a Cesarean section delivery always cost more than a vaginal delivery? AB - There is evidence that average total charges per episode of child birth depend on maternal plus child length of stay, neonatal intensive care unit (NICU) utilization, maternal race and mode of delivery. In particular, when maternal and child records are linked, this study suggests that when adjusted for maternal characteristics, the cost of vaginal deliveries followed by NICU utilization may be higher than the cost of Cesarean sections and NICU utilization. OBJECTIVE: Cesarean section, one of the most frequently performed surgical procedures on women, is rising globally and in the USA. Much of the current Cesarean section literature focuses on reporting geographic and hospital-specific variations, but little has been published about the clinical and demographic characteristics of the patients, and even less about the economic consequences of a Cesarean section delivery compared with a vaginal delivery [e.g. the total hospital charges and length of neonatal intensive care unit-NICU-stay] of a birth episode. To examine these relationships further, three urban Baltimore hospitals volunteered in 2004 to participate in a retrospective chart review that linked mother and child hospital records. METHODS: 1172 mother-child records were randomly selected and data regarding maternal co-morbidities, age, infant weight along with transfer to neonatal intensive care units, and economic data were extracted from the mother and child charts. CONCLUSION: Average total charges for vaginal deliveries [maternal plus total baby charges that includes NICU utilization (X=$17 624.38)] may be higher than average total charges for Cesarean sections [maternal plus total baby charges that includes NICU utilization (X=$13 805.47)]. Specifically, maternal race--being African American--was indirectly associated with overall charges through its association with mode of delivery and NICU utilization patterns. The presence of maternal co-morbidities--Herpes Simplex Virus, hypertension and diabetes--most probably influenced babies' hospital stay charges as well as NICU charges when transferred to NICU following both vaginal and Cesarean section deliveries. Thus, prenatal care targeting co-morbidities management may reduce the odds of a newborn's transfer to NICU thus avoiding greater lengths of stay, medical care and charges. Recommendations for obstetrical practices as well as health care policy on their charges should not assume that Cesarean section deliveries are always costlier than vaginal deliveries. PMID- 17286719 TI - The inappropriate use of HbA1c testing to monitor glycemia: is there evidence in laboratory data? AB - RATIONALE, AIMS AND OBJECTIVES: Diabetes is a chronic illness and have relatively high prevalence. Glycemic control is fundamental to the management of diabetes. Hemoglobin A1c (HbA1c) is a commonly used laboratory test to monitor glycemia and to manage diabetes. This study aimed to assess the appropriateness of the frequency of HbA1c test order with respect to the commonly approved guidelines for monitoring glycaemia of patients. METHODS: To assess the rate of inappropriate test orders, laboratory records of HbA1c tests ordered between 2002 and 2004 were evaluated. Inappropriate orders were defined as any order for a given patient that takes place within a 29- or 89-day-period following the previous HbA1c order. The effects of various parameters, like ordering clinics, the first HbA1c level, or the on-line availability of test results on test ordering were evaluated. RESULTS: Evaluation of test intervals showed that 10.3% of all orders and 33.8% of the inpatients' orders were performed within 29 days, 35.5% of all orders and 55% of the inpatients' orders were within 89 days. CONCLUSIONS: Inappropriate laboratory utilization of HbA1c testing is very common especially in the inpatient clinics. We think that the application of the guidelines may decrease unnecessary health expenditure. PMID- 17286720 TI - Diurnal variation of prescribing pattern of primary care doctors in Bahrain. AB - RATIONALE, AIMS AND OBJECTIVES: To evaluate the variation in prescribing by primary care doctors during the morning and the evening clinics and to determine whether these prescribing patterns are influenced by doctors' training background. METHODS: A retrospective prescription-based study was carried out in 17 out of 20 primary care health centres in Bahrain distributed across the Kingdom. RESULTS: A total of 4472 prescriptions containing 10 588 drug-items covering the prescribing practice of approximately 90% primary care doctors were analysed. Paracetamol was the most commonly prescribed drug in both clinics. Drugs such as diclofenac sodium, amoxycillin, ibuprofen, chlorpheniramine, hyoscine butylbromide, Actifed, Benylin and xylometazoline were the most commonly prescribed drugs to patients attending morning and evening clinics with a considerable variation in ordinal ranking of proportions. As regards morning clinic, chlorpheniramine and Fefol were prescribed by the family doctors (FDs) more often than by the general practitioners (GPs) (P<0.05), whereas, multivitamins were prescribed by the GPs more often than by the FDs (P=0.001). During the evening clinic, however, ibuprofen, chlorpheniramine, bromhexine and xylometazoline were prescribed by the FDs in a rate significantly higher than that prescribed by the GPs (P<0.05). The prevalence of acute and/or chronic morbidities in patient attending clinics was estimated based on the therapeutic indication for drugs used. The mean number of drugs per prescription was 2.41+/ 1.3. Prescriptions containing three or more drugs comprised 41.7% of all prescriptions. The GPs had a greater tendency to practice polypharmacy than the FDs. CONCLUSION: A significant diurnal variation in prescribing, and polypharmacy practice were related to the training background of the doctors. This quantitative study provides the baseline data for monitoring primary care prescribing practices in Bahrain. To further evaluate the underlying factors that influence drug use indicators, a qualitative study is needed. PMID- 17286721 TI - The Patient Satisfaction Scale--an empirical investigation into the Finnish adaptation. AB - RATIONALE AND AIMS: The aim of this paper is to empirically investigate the performance characteristics of the Finnish adaptation PSS-Fin of the Patient Satisfaction Scale (PSS) intended to measure patient satisfaction with nursing care. The PSS-Fin includes three sub-scales: technical-scientific, informational and interaction/support care-needs. METHODS: The PSS-Fin was used in a cross sectional survey measuring the satisfaction of Finnish surgical patients (n=454) with the nursing care they received. The feasibility, internal consistency, stability, equivalence and construct validity of the measure were investigated. Evaluation was based on statistical methods. RESULTS: The PSS is brief and easy to use, and it produced low missing data. Cronbach's alpha coefficient ranged from 0.79 to 0.89 for the sub-scales. The items correlated strongly with the sub scales and the sub-scales with the total PSS as well. Test-retest reliability of 0.7 showed reasonable stability over time. Three factor analytic procedures supported for the three-factor solution with a technical-scientific, informational and interaction/support factors, explaining approximately 77% of the variance. The PSS had some equivalence with another satisfaction instrument, but also exhibited the ability to discriminate between each other. In multiple regression analysis the informational care-needs sub-scale was the most significant factor explaining patient satisfaction. CONCLUSION: The PSS-Fin demonstrated good psychometric properties and conceptual rigour and is thus reliable tool for examining patient satisfaction with nursing care. PMID- 17286722 TI - Seven reasons why health professionals search clinical information-retrieval technology (CIRT): toward an organizational model. AB - RATIONALE AND AIM: Clinical Information-Retrieval Technology (CIRT) is increasingly used, for example in accessing drug databases. However, no comprehensive framework exists to understand why health professionals search for information using CIRT. The present article aims to propose such organizational framework. BACKGROUND: Our literature review suggests six reasons, of which three refer to cognitive objectives (C1, C2, C3) and three to organizational objectives (O1, O2, O3): (C1) to answer-solve-support a clinical question-problem-decision; (C2) to fulfil an educational-research objective; (C3) to search in general or for curiosity; (O1) to share information with patients; (O2) to exchange information with other health professionals; (O3) to plan-manage-monitor tasks with other health professionals. METHODS: The case study examined the use and impact of the InfoRetriever software on handheld computers in a Canadian family practice centre. Using the Critical Incident Technique, six family doctors were interviewed on specific events. A thematic analysis assigned extracts of interviews to reasons for use. FINDINGS AND CONCLUSION: Findings illustrate the six reasons, and suggest a seventh reason that refers to a cognitive objective, namely (C4) to overcome the limits of health professional memory. These seven reasons are interpreted according to the literature on information science and organization studies, which suggest ordering reasons at three levels of stimulation of learning and knowledge: none (objective not achieved), moderate (cognitive objective achieved), and high (organizational objective achieved). This paves the way toward a new evaluation of relevance of CIRT in everyday practice (judgement based on professionals' objective achievement) using an organizational model of information-retrieving processes. PMID- 17286723 TI - The Finnish national asthma programme: communication in asthma care--quality assessment of asthma referral letters. AB - AIMS AND OBJECTIVES: The Finnish National Asthma Programme, which was launched in year 1994, considered the management of asthma as a community problem. The role of the primary health care in the management of asthma was emphasized. Optimal asthma management includes good communication between health care professionals. Referral letters are an accepted tool for evaluation of the communication process. The aim of this study was to assess the quality of asthma-related referral letters. METHODS: All non-acute referral letters (n=3176) to three pulmonary departments were screened in 2001 and all those related to asthma were included (n=1289). The 14 previously derived asthma-specific criteria were applied: occupation, smoking, known allergies, current medication, other diseases, onset of symptoms, wheezing, dyspnoea, specified dyspnoea, cough, specified cough, use of asthma medication, peak-flow follow-up or spirometry with bronchodilatation test as an attachment. The study group was prepared to accept the maximum of 30% of the referral letters to be of poor quality. RESULTS: Twenty one per cent of the referral letters were graded good, 34% satisfactory and 45% poor. Information on wheezing, smoking habits and current medication was mentioned in 44%, 42% and 41% of asthma letters respectively. CONCLUSIONS: The Finnish National Asthma Programme calls for optimizing communication between doctors. The proportion of poor letters was 50% higher than the preset standard and clearly indicates a need for improvement. We found several issues, which need to be better communicated (smoking, lung function tests, wheezing, medication) when referring a patient with suspected asthma. PMID- 17286724 TI - Groups or teams in health care: finding the best fit. AB - RATIONALE: In the evolution of the team concept, clear distinctions between 'groups' and 'teams' were made. In this paper we argue that these distinctions were not made explicit in the translation of team structures to health care. Even though teams are appropriate for many health care settings, this paper explores the notion that when teams may not be working, it is the concept of team that may not be appropriate, not the functioning of the team itself. METHODS: This paper reviews the differences between teams and groups, and identifies how these differences are expressed in health care settings using urban and rural examples from the UK and Australia. RESULTS: Some suggestions about matching structures to suit the unique nature of health care provision, particularly in community health settings, are made. DISCUSSION: Instead of concentrating on improving the process of teams, the focus could be better directed to ensure that whatever structure is utilized best facilitates the necessary outcomes in the most effective way. The team approach may not always be the best approach, and sometimes referring to a number of people working together as a group is sufficient. PMID- 17286725 TI - Quality evaluation of total parenteral nutrition in an acute care setting. AB - OBJECTIVE: To analyse the degree of compliance with internationally accepted standards defined for total parenteral nutrition (TPN) quality control in our hospital. The problems of quality which exist must be detected and possible solutions put into practice. PATIENTS AND METHOD: Retrospective study of critically ill patients treated with TPN during two years in a university teaching hospital (n=92). Assessment of quality was performed through measurements of compliance using 20 criteria. These were evaluated both individually and gathered in three categories: appropriate, safe and accurate TPN. Three summary/indicators were also established which assessed simultaneous compliance with all the criteria in each group. Criteria compliance was compared to standards values. Patient (age, sex, diabetes) and process (TPN indication, patient's outcome, type of diet used) variables were analysed (using logistic regression models) as factors potentially associated with compliance with the quality criteria. Corrective measures aimed at resolving the quality problem were applied to the deficient criteria, paying particular attention to those criteria which presented the highest percentage of errors in the study carried out using a Pareto analysis. RESULTS: Compliance of six criteria was significantly below standard values. Simultaneous compliance of all criteria by group was 17% in adjusted TPN, 38% in safe TPN and 94% in exact TPN. There was a negative association between an age over 65 years and both a correct indication of TPN (OR: 9.4) and the indicator compliance of all criteria in the adjusted TPN group (OR: 2.9). The absence of metabolic complications was influenced (P<0.05) by the use of standardized diets (OR: 0.3). Effects of the change: the simultaneous compliance with all the criteria of a group improved in all three groups, but this was statistically significant in the 'appropriate' TPN and 'safe' TPN groups. The criteria analysed individually improved after the corrective measures in five of the six criteria which had been below standard in the first evaluation. CONCLUSIONS: The correct understanding and application of the indications, physiology and potential complications of TPN constitute the hub of the improvement process. PMID- 17286726 TI - Economic analysis for clinical practice--the case of 31 national consensus guidelines in the Netherlands. AB - RATIONALE, AIMS AND OBJECTIVE: Evidence on the cost-effectiveness of health interventions in the development of practice guidelines has become of interest in many countries. Challenges are the quality of economic data, the use of cost effectiveness criteria, and the consensus process. Our paper aims to assess the quality and use of economic information in the formulation of consensus guidelines in a Dutch pilot programme and to recommend improvements. METHODS: Retrospective qualitative review of economic evaluations and formulated recommendations, using a checklist based on international standards. RESULTS: The national programme to support the development of guidelines with economic analysis in multidisciplinary consensus groups run from 1998 to 2002. It has included 31 medical guidelines, addressing 23 conditions across seven International Classification of Diseases (ICD)-disease groups. Experts in health technology assessment have participated in the guidelines groups. Economic information in all guidelines varies by all criteria in the level of evidence used. Information on quality-adjusted life years gained is limited as is statistical analysis in most studies. Highest cost-effectiveness ratios reported are between Euros 20,000 and Euros 30,000. However, there is no uniformity in the definitions of acceptable cost-effectiveness ratios. CONCLUSIONS: Economic recommendations can be included in guidelines. Interaction between clinicians and health economists promotes a balance between medical and economic arguments. Among panellists there appears to be agreement on the level of the cost effectiveness ratios that is acceptable. It is recommended that economic analysis is used to strengthen the evidence-base of guidelines. An evidence-grading system should include the quality of economic evaluation. Roles of policymakers and providers need to be defined. PMID- 17286727 TI - A novel method for evaluation of improved survival trend for common cancer: early detection or improvement of medical care. AB - RATIONALE, AIMS AND OBJECTIVES: The improvement of survival with time for cancers has been observed worldwide. However, whether and to what extent such an improvement is attributed to early detection or the advance in medical technology is barely addressed. METHOD: We developed a novel graphic method to calculate attributable proportions related to two factors. This graphic method was first to calculate adjusted survival curve by the application of direct standardized epidemiological method to tumour staging. The crude survival curve was then compared with the adjusted survival curve. RESULTS: Cumulative survival curves of two time epochs, 1989-1993 (period 1) and 1994-1998 (period 2), on six common cancers collected from cancer registry of National Taiwan University between 1989 and 1998, were compared. The attributable proportions due to early detection and medical care were 77% and 23% for breast cancer, 50% and 50% for cervical cancer, 52% and 48% for colorectal cancer, 76% and 24% for gastric cancer, 66% and 34% for liver cancer, and 30% and 70% for prostate cancer respectively. CONCLUSION: Distinguishing between early detection from advance in medical care associated with the improvement of survival trend using our graphic method has a significant implication for secondary and tertiary prevention of common cancers. PMID- 17286728 TI - Attitudes of genetic clinicians in Wales to the future development of cancer genetics services. AB - RATIONALE: Cancer genetics is one of the fastest-growing areas of clinical genetics and it is imperative to identify how services should be organized and delivered in the future. METHODS: A qualitative study utilizing focus group methodology which explored the attitudes of clinicians working in the Medical Genetics Service for Wales to a number of possible models for future service delivery. RESULTS: There was no consensus for any particular model. Greater involvement of primary care practitioners is anticipated, but this requires investment in information, education and professional development initiatives. Self-referrals were not encouraged, though the promotion of genetic literacy amongst the general population was supported, particularly in conjunction with pharmacists. CONCLUSION: As demand for cancer genetics services continues to increase, some consensus about the future delivery of such services is necessary. Consultation with other stakeholder groups, especially primary care practitioners and patients, should also contribute to service planning. PMID- 17286730 TI - The patient experience of community hospital--the process of care as a determinant of satisfaction. AB - AIMS AND OBJECTIVES: We report findings from a qualitative study to identify patient views of community hospital care. We consider how far these were in accord with the hospital staffs' views. This constituted part of a wider randomized controlled trial (RCT). The methodological challenges in seeking to identify patient satisfaction and in linking qualitative findings with trial results are explored. DESIGN: A sample of 13 patients randomized to the community hospital arm of the RCT joined the qualitative study. Official documentation from the hospital were accessed and six staff interviewed to identify assumptions underlying practice. RESULTS: Analysis of interviews identified a complex picture concerning expectations These could be classified as ideal, realistic, normative and unformed. The hospital philosophy and staff views about service delivery were closely in harmony, they delivered rehabilitation in a home-based atmosphere. The formal, or 'hard', process of rehabilitation was not well understood by patients. They were primarily concerned with 'soft' or process issues--where and how care was delivered. CONCLUSIONS: We identify a model of community hospital care that incorporates technical aspects of rehabilitation within a human approach that is welcomed by patients. If patients are to be able to participate in making informed decisions about care, the rationale for the activities of staff need to be more clearly explained. Recommendations are made about the appropriate scope of qualitative findings in the context of trials and about techniques to access patient views in areas where they have difficulty in expressing critical impressions. PMID- 17286729 TI - Evaluation of a service development to implement the top three process indicators for quality stroke care. AB - RATIONALE, AIM AND OBJECTIVE: Stroke mortality remains unacceptably high with up to 30% of patients dying within 1 month. Early swallow screen and computerized tomography (CT) brain scan, facilitate delivery of aspirin, which together are recognized as the top three process indicators for quality stroke care. Evidence indicates that treatment with aspirin (300 mg) saves lives and should commence within 48 h of stroke onset. However, many hospitals find it difficult to meet this timescale. We aimed to evaluate whether reorganization of services could improve aspirin delivery following acute ischaemic stroke. METHOD: A retrospective audit was carried out to determine the time to swallow screen, CT scan and aspirin administration. A service review was conducted and the findings disseminated. A decision was made to reorganize services by enhancing the role of senior nursing staff to: (1) admit patients, (2) request CT brain scans, (3) screen for swallowing abnormality, and (4) prescribe the first dose of aspirin. A second audit was conducted to evaluate the impact of the new service. RESULTS: Before reorganization, 30% had swallowing screened and 38% had CT scans within 24 h. Thirty-one per cent received their first dose of aspirin within 48 h. After reorganization, 68% had their swallowing screened and 80% had a CT scan within 24 h. Ninety per cent of patients received their first dose of aspirin within 48 h. CONCLUSIONS: Modernizing service delivery by changing traditional roles can offer quality solutions ensuring that aspirin delivery is expedited by early swallow screen and CT scan. These initiatives could be used more widely to improve patient care and implement the top three process indicators for stroke. PMID- 17286731 TI - Racial differences in treatment preferences: oral health as an example. AB - RATIONALE, AIMS AND OBJECTIVES: Recent analyses from the Florida Dental Care Study found that response to a hypothetical scenario at baseline strongly predicted: (a) tooth loss during follow-up; and (b) subsequent receipt of either a dental extraction or Root Canal Therapy (RCT). The scenario ('CHOICE') required choosing either to: (1) extract the tooth before even knowing the cost of treatments; (2) extract, but after knowing the cost of all treatments; or (3) have RCT despite knowing costs. OBJECTIVE: The purpose of this study was to identify factors associated with CHOICE and quantify their effects. METHODS: As part of the baseline phase of the study, 873 subjects with at least one tooth and who were 45 years or older participated for an interview and dental examination. A multinomial multivariable regression of CHOICE quantified effects due to hypothesized predictors. RESULTS: CHOICE was strongly associated with race (African-Americans were significantly less likely to choose RCT). Results from the multivariable regression suggest that the race effect could be explained by racial differences in patient preference, treatment acceptability and ability to afford treatment. CONCLUSIONS: There were substantial racial differences in treatment preference even in this hypothetical scenario where racial differences in patient-provider interaction and clinical factors were not relevant. Certain predisposing and enabling variables explained these racial differences in treatment preference. PMID- 17286732 TI - The usefulness and feasibility of a reflexivity method to improve clinical handover. AB - OBJECTIVE: The evaluation of the usefulness and feasibility of the reflexivity method (RM), which encourages dialogue and reflections between doctors, and enables change. METHODS: On the basis of literature research into effective medical professional learning and reflection, essential elements that stimulate reflection and learning were distinguished and converted into the basic elements of a method developed for this purpose, the RM. The method is used as a tool to stimulate reflection processes, which, in turn, will enable change. It was used 20 times in a large university medical centre in the Netherlands. Clinical handovers were the subject of reflection. The evaluation of the usefulness and feasibility of the RM is based on analysing the improvements realized by using the method, and a questionnaire to measure the experiences of the users of the method. RESULTS: Each of the 17 departments evaluated received 10 recommendations on average. Fifty-eight per cent of these were realized after 6-9 months, and 18% were in the working-out phase. Improvements in the structure, rules and protocols concerning handovers were realized as well as in the atmosphere. The users of the method evaluated the method overall positively: they appreciated the created context for reflection, that is, having a dialogue with a colleague working at the same hierarchical level, the non-normative character of the method and the 'doctor-ownership' of the method. They also reported an effect on their handling and thinking regarding handovers. CONCLUSIONS: The RM seems to be a useful and feasible method to stimulate the doctors' reflection processes, resulting in implemented improvements. PMID- 17286733 TI - Using semantic differentials in fieldwork. AB - RATIONALE: A large project was undertaken to examine attitudes and opinions of health staff and parents about the care of hospitalized children in four countries. A simple scoring system, which allowed comparisons between results from each country, was needed to examine concepts under investigation. AIMS AND OBJECTIVES: This paper describes how, after trialling a range of methods, semantic differentials (SD) were found to be easy for the subjects to use. They translated well into other languages and provided scores which were easy to analyse and compare. RESULTS: Semantic differentials are based on a series of line scores using adjectives and their antonyms for a set of characteristics. They are a particularly useful method for fieldwork analysis, as they can be done by hand with no computer support. CONCLUSIONS: Semantic differentials were found to be useful for cross-cultural, quantitative studies of this kind. I discuss SDs, how they work, their trialling, reliability and validity and their usefulness in cross-cultural research. PMID- 17286734 TI - Parent implemented early intervention for young children with autism spectrum disorder: a systematic review. AB - BACKGROUND: Recent estimates concerning the prevalence of autism spectrum disorder (ASD) suggest that at least one in 200 children is affected. This group of children and families have important service needs. The involvement of parents in implementing intervention strategies designed to help their autistic children has long been accepted as helpful. The potential benefits are increased skills and reduced stress for parents as well as children. METHODS: This research review focused on interventions for children aged 1-6 years, and was carried out using systematic methodology: a comprehensive search of psychological, educational and biomedical databases, as well as bibliographies and reference lists of key articles, contact with experts in the field, and hand search of key journals. Only studies which involved a concurrent element of control were included. RESULTS: The review found very few studies that had adequate research design from which to draw conclusions about the effectiveness of parent-implemented early intervention. Both randomized and controlled studies tended to suggest that parent training leads to improved child communicative behaviour, increased maternal knowledge of autism, enhanced maternal communication style and parent child interaction, and reduced maternal depression. CONCLUSION: It seems that parent training can successfully contribute to intervention for young children with ASD. However, the review highlights the need for improved research in this area. PMID- 17286735 TI - Recording of drug allergies: are we doing enough? AB - OBJECTIVE: To assess the implementation of local and national guidelines concerning documentation of drug/clinical hypersensitivities. DESIGN: Audit with retrospective and prospective components used to assess the process of drug hypersensitivity documentation. PATIENTS: Fifty surgical inpatients' notes were retrospectively analysed followed by 63 patients prospectively. SETTING: West London teaching hospital. MAIN OUTCOME MEASURES: Drug hypersensitivity status correctly indicated on clinical notes, drug 'Kardex' charts, and anaesthetic records; these three documents were to concur. Hypersensitivities qualified according to symptoms experienced. RECOMMENDATIONS: Standardization of preoperative clinical notes and multidisciplinary responsibility for records between doctor, nurse and pharmacist. RESULTS: Hypersensitivity documentation in clinical notes improved by 7% after the introduction of a formalized history sheet for preoperative clinics. These were based upon the anaesthetic charts, which had demonstrated 100% documentation previously. Considerable improvements (70.8%) in the clarification of adverse reaction symptoms post recommendation were shown; this was also attributed to the new history sheet. Concurrence improved by 2%. CONCLUSIONS: The original study revealed areas for improvement and provided part of the solution--a more standardized preoperative assessment tool. Multidisciplinary cooperation in addition to formalizing the assessment process has led to a more efficient and safer service for patient and medicolegally for health care professionals. KEY MESSAGES: (1) Standardized forms, for the recording of clinical information preoperatively, ensure relevant guidelines are implemented in practice. (2) Multidisciplinary teams provide a vital safety net for their patients and colleagues. PMID- 17286736 TI - Diagnostic errors and reflective practice in medicine. AB - BACKGROUND: Adverse effects of medical errors have received increasing attention. Diagnostic errors account for a substantial fraction of all medical errors, and strategies for their prevention have been explored. A crucial requirement for that is better understanding of origins of medical errors. Research on medical expertise may contribute to that as far as it explains reasoning processes involved in clinical judgements. The literature has indicated the capability of critically reflecting upon one's own practice as a key requirement for developing and maintaining medical expertise throughout life. OBJECTIVES: This article explores potential relationships between reflective practice and diagnostic errors. METHODS: A survey of the medical expertise literature was conducted. Origins of medical errors frequently reported in the literature were explored. The potential relationship between diagnostic errors and the several dimensions of reflective practice in medicine, brought to light by recent research, were theoretically explored. RESULTS AND DISCUSSION: Uncertainty and fallibility inherent to clinical judgements are discussed. Stages in the diagnostic reasoning process where errors could occur and their potential sources are highlighted, including the role of medical heuristics and biases. The authors discuss the nature of reflective practice in medicine, and explore whether and how the several behaviours and reasoning processes that constitute reflective practice could minimize diagnostic errors. Future directions for further research are discussed. They involve empirical research on the role of reflective practice in improving clinical reasoning and the development of educational strategies to enhancing reflective practice. PMID- 17286737 TI - Accessing rural populations: role of the community pharmacist in a breast and cervical cancer screening programme. AB - RATIONALE: Community pharmacists are one of the most frequently visited health care providers in the USA. The article describes a demonstration project which used community pharmacists to educate and enrol low to moderate income and medically under-served women into a statewide breast and cervical cancer screening programme. METHODS: The Nebraska Department of Health programme entitled, 'Every Woman Matters', funded through the Centers of Disease Control and Prevention, provided no cost or low cost mammography and pap smears to eligible women. Patient enrolment packets were distributed to 91 pharmacies expressing an initial interest in participating. These were reduced to 28 pharmacies based on their commitment level during the initial 3 months of the study. RESULTS: One hundred and fourteen patient referrals were generated from the 28 network pharmacies; two from pharmacies in urban areas, and 112 referrals from rural sites. All referrals were from the 22 independently owned pharmacies in the study. CONCLUSIONS: Results suggest that the use of independent community pharmacies in the rural setting can be an effective method of recruiting women into public health programmes. PMID- 17286739 TI - Patients' preferences shed light on the murky world of guideline-based medicine. AB - Concordance--that is, shared decision-making between doctors and patients--is nowadays accepted as an integral part of good clinical practice. It is of particular importance in the case of treatments with only marginal benefits such as those recommended in guidelines for the management of common, chronic diseases. However, the implementation of guideline-based medicine conflicts with that of concordance. Studies indicate that patients are not adequately informed about their treatment. Clinical guidelines for conditions such as cardiovascular disease are based on large-scale randomized trials and the complex nature of the data limits effective communication especially in an environment characterized by time constraints. But other factors may be more relevant, notably pressures to comply with guidelines and financial rewards for meeting targets: it is simply not in the interests of doctors to disclose accurate information. Studies show that patients are far from impressed by the small benefits derived from large scale trials. Indeed, faced with absolute risk reductions, patients decline treatment promoted by guidelines. To participate in clinical decisions, patients require unbiased information concerning outcomes with and without treatment, and the absolute risk reduction; they should be told that most patients receiving long-term medication obtain no benefit despite being exposed to adverse drug reactions; furthermore, they should be made aware of the questionable validity of large-scale trials and that these studies may be influenced by those with a vested interest. Genuine concordance will inevitably lead to many patients rejecting the recommendations of guidelines and encourage a more critical approach to clinical research and guideline-based medicine. PMID- 17286738 TI - Overall self-rated health: a new quality indicator for primary care. AB - RATIONALE, AIMS AND OBJECTIVES: Patient 'empowerment' gives patients choices about their own care and about the outcomes they would most prefer. Many patients can be presumed to regard overall self-rated health as an important outcome. Therefore, overall self-rated health can be considered a relevant and important outcome measure for a patient-centred medical clinic. The purpose of this study was to use this new outcome measure as a dependent variable and to test the hypothesis that patients who are confident about their ability to manage their health will have better health, in comparison to more dependent patients. METHODS: We conducted a randomized cross-sectional postal survey of 500 veteran patients from the Panhandle of Texas and the surrounding areas; and 302 participated in the study. Multiple logistic regression analysis was used to test the hypothesis that health confidence is positively related to self-rated health, controlling for obesity, cigarette smoking and participation in recreational activities. RESULTS: Veterans who strongly disagreed with the statement that they usually could overcome illnesses on their own were less likely to report good, very good or excellent self-rated health (adjusted odds ratio=0.25). CONCLUSIONS: Overall self-rated health as measured by a single question proved to be significantly related to behavioural risk factors in this sample of primary care patients, attesting to its validity as an outcome indicator. Furthermore, health confidence was associated with better health. Most primary providers believe that they can, through good communication and providing self-care tools, increase healthy behaviours in their patients. If we are indeed able to increase health confidence in our patients, this study would suggest that self-rated health would improve. PMID- 17286740 TI - Melatonin decreases nitric oxide production and lipid peroxidation and increases interleukin-1 beta in the brain of mice infected by the Venezuelan equine encephalomyelitis virus. AB - Melatonin, a potent antioxidant, has shown to be beneficial in murine Venezuelan equine encephalomyelitis (VEE) virus infection. In addition, melatonin can induces the production of interleukin-1 beta (IL-1beta), a cytokine capable of inducing increased expression of inducible nitric oxide synthase; the activity of this enzyme is increased in the brain of mice infected with VEE virus. The aim of this study was to determine the effect of VEE virus on the nitric oxide (NO) production, lipid peroxidation and IL-1beta production in the brain and serum of mice infected with VEE virus, and to investigate the modulatory role of melatonin during this viral infection. Mice were infected with 10 LD(50) of VEE virus and treated with melatonin (500 microg/kg of body weight) starting 3 days before and continuing for 5 days after virus inoculation. Mice were sacrificed on days 1, 3 and 5 postinfection and brains and blood samples were obtained. NO and IL-1beta production and lipid peroxidation levels were measured in perfused brain homogenates and serum. Increased production of brain nitrite was found on days 1, 3 and 5 postinfection and lipid peroxidation products were increased at day 5. Levels of serum nitrite were found elevated on days 3 and 5 postinfection; however, lipid peroxidation products remained similar to basal levels. Melatonin treatment decreased nitrite concentration in brain and serum of infected mice as well as the lipid peroxidation products in the brain. IL-1beta was found to be increased in the brain and serum of infected animals, and melatonin treatment induced higher levels of this cytokine (brain: about 4-fold; serum: about 8 fold). These results may be related to the beneficial effect of melatonin in the VEE experimental disease and address the possible therapeutic potential of the indoleamine in human VEE virus infection. PMID- 17286741 TI - Ventricular cerebrospinal fluid melatonin concentrations investigated with an endoscopic technique. AB - The role of melatonin in humans still remains unclear. Uncertainties persist about its effects on neurophysiology regarding its levels in human cerebrospinal fluid (CSF), as the bulk of knowledge on this subject mainly derives from studies conducted on animals. In this study, CSF was micro-sampled with a simple, new method from each cerebral ventricle of patients undergoing neuroendoscopy for hydrocephalus. Our purpose was to measure CSF melatonin levels and determine possible differences in its concentration among various significant areas in the cerebral ventricles (e.g. pineal recess, pituitary recess, lateral ventricle, fourth ventricle) and lumbar cistern. From 2002 to 2004, 10 hydrocephalic patients were operated on using a neuroendoscopic technique. The CSF specimens were investigated for melatonin concentrations (free plus protein-bound) after deproteinization; the measurement technique was high-performance liquid chromatography. The preliminary data obtained with this endoscopic micro-sampling technique (applied to humans for the first time) suggest that melatonin is more concentrated within the ventricles and its highest concentration is found in the third ventricle (IIIv), although the difference detected between the CSF of the IIIv and that of the pineal recess was not significant. PMID- 17286742 TI - Increased melatonin concentrations in children with growth hormone deficiency. AB - A relationship between melatonin and growth hormone (GH) is poorly understood. We compare circadian melatonin rhythms in short children with normal and decreased GH secretion. The analysis included 22 children (20 boys and 2 girls) aged 11.1 16.9 yr (mean +/- S.E.M. = 14.1 +/- 0.3 yr) with short stature (height SDS below 2.0). Based on the GH peak in stimulation tests patients were divided into two groups: idiopathic short stature (ISS, n = 11; GH peak > or = 10 ng/mL) and GH deficiency (GHD, n = 11; GH peak < 10 ng/mL). In all patients the circadian melatonin rhythm was assessed on the basis of nine blood samples, collected in 4 hr intervals during the daytime and 2-hr intervals at night, with dark period lasting from 22:00 to 06:00 hr. Magnetic resonance imaging examination excluded organic abnormalities in central nervous system in all patients. Melatonin concentration at 24:00, 02:00 and 04:00 hr as well as the area under curve of melatonin concentrations (AUC) were significantly higher in the patients with GHD than in individuals with ISS. Significant correlations between GH secretion and melatonin concentrations at 24:00, 02:00 and 04:00 hr, and AUC were also observed. On the basis of these data it seems that the assessment of nocturnal melatonin secretion might be a valuable diagnostic tool used for the improvement of the difficult diagnosis of short stature in children. PMID- 17286743 TI - Melatonin inhibits maneb-induced aggregation of alpha-synuclein in rat pheochromocytoma cells. AB - Melatonin, a secretory product of the pineal gland, is involved in the regulation of circadian and seasonal rhythms, in oncostasis, and in inducing osteoblast differentiation. Furthermore, melatonin is a scavenger of a number of reactive oxygen and reactive nitrogen species both in vitro and in vivo. In this study, the antioxidant nature of melatonin was shown to prevent cultured neural cells from apoptosis induced by endocrine-disrupting chemical, maneb. The neurotoxicity of the fungicide, maneb (1 microg/mL), on the PC12 cells was elicited through apoptotic cell death, concomitant with aggregation of alpha-synuclein, a feature of Parkinson's disease. Activation of caspase-3/7 was associated with this process. A fluorescence rationing technique using a mitochondrial dye revealed that maneb altered the mitochondrial membrane potential of the neural cells. However, melatonin (1 nm) largely prevented the neural cells from the neural toxicant by inhibition of both caspase-3/7 activation and disruption of the mitochondrial transmembrane potential. Furthermore, aggregation of alpha synuclein by maneb was also inhibited by melatonin. Thus, melatonin prevents maneb-induced neurodegeneration at a nighttime physiological blood concentration, most likely by inhibiting the aggregation of alpha-synuclein as well as preventing mitochondrial dysfunction in PC 12 cells. PMID- 17286744 TI - Inhibition of proliferation and induction of apoptosis by melatonin in human myeloid HL-60 cells. AB - Melatonin is an indoleamine that is synthesized in the pineal gland and has an extensive repertoire of biological activities. In the present study, we found that melatonin reduced the growth of the human myeloid leukemia cells HL-60, inhibiting progression from G(1) to S phase of the cell cycle and increasing apoptotic cell death. Furthermore, melatonin treatment elevated cytochrome c release from mitochondria and augmented caspase-3 and caspase-9 activities. Upregulation of Bax and downregulation of Bcl-2 was also observed upon melatonin treatment. The effects of melatonin were found not to be mediated by membrane receptors for the indoleamine. Together, our results suggest that melatonin reduces the viability of HL-60 cells via induction of apoptosis primarily through regulation of Bax/Bcl-2 expression. PMID- 17286745 TI - Long-term morphological and functional evaluation of the neuroprotective effects of post-ischemic treatment with melatonin in rats. AB - Consensus on neuroprotection has pointed out the relevance of the long-term morphological and functional evaluation of the effectiveness of putative neuroprotective procedures. In the present study, place learning (Morris water maze) and working memory (eight-arm Olton radial maze) were evaluated in adult male rats 90 days after 15 min of global cerebral ischemia (four-vessel occlusion) followed by continuous i.v. infusion (10 mg/kg/hr) of melatonin (Isch + Mel) or vehicle (Isch + Veh) for 6 hr, and the pyramidal neuron population of the cornus Ammoni (CA) of the hippocampus and layers III and V of the medial prefrontal cortex was assessed at the end of the behavioral testing period (120 days after ischemia). Impairment of place learning, a significant delay in working memory acquisition, and a significant loss of pyramidal neurons in the Ammon's horn (CA1: 23%, CA2: 52% CA3: 73%, hilus: 64% remaining neurons), were observed in the Isch + Veh group. By contrast, a similar performance of the Isch + Mel group to that in the Intact and Sham groups and better than that of the Isch + Veh group, besides a significant reduction of pyramidal neuron loss in the CA subfields (CA1: 79%, CA2: 88% CA3: 86%, hilus: 72% remaining neurons), documented that melatonin treatment led to a long-term preservation of both the neural substrate, and the capability for integration of spatial learning and memory, mainly dependent on a normal hippocampal functioning. Overall the results emphasize the efficacy of melatonin in counteracting the pathophysiological processes induced by ischemia, by exerting its actions during a short but critical period early after the ischemic episode. PMID- 17286746 TI - Melatonin promotes adventitious- and lateral root regeneration in etiolated hypocotyls of Lupinus albus L. AB - Melatonin is a well-known animal substance, which has recently been detected in plant tissues. However, there are only a few studies concerning its possible physiological role in plants. In this paper, we investigate the possible effect of melatonin on the regeneration of lateral and adventious roots in etiolated hypocotyls of Lupinus albus L. compared with the effect of indole-3-acetic acid. We performed this study by measuring both molecules in roots. Six-day-old derooted lupin hypocotyls immersed in several melatonin or indole-3-acetic acid concentrations were used to induce roots. A macro- and microscopic study of the histological origin of the adventitious and lateral roots was made, while melatonin and indole-3-acetic acid in the roots were quantified using liquid chromatography with fluorescence detection. The data show that both melatonin and indole-3-acetic acid induced the appearance of root primordia from pericicle cells, modifying the pattern of distribution of adventitious or lateral roots, the time-course, the number and length of adventitious roots, and the number of lateral roots. Melatonin and indole-3-acetic acid were detected and quantified in lupin primary roots, where both molecules were present in similar concentrations. The physiological effect of exogenous melatonin as root promoter was demonstrated, its action being similar to that of indole-3-acetic acid. PMID- 17286747 TI - Effect of melatonin on the oxidative stress in erythrocytes of healthy young and elderly subjects. AB - The disturbances in pro- and antioxidant balance may play an important role in the pathomechanism of aging. The pineal hormone melatonin, which exerts effective antioxidative properties, is suggested to be involved in the aging process. The aim of this study was to compare the oxidative stress in erythrocytes of healthy young adults and elderly people, and to determine the influence of melatonin supplementation on measured parameters in both examined groups. The malondialdehyde (MDA) and reduced glutathione levels as well as Cu-Zn superoxide dismutase (SOD-1), catalase, glutathione peroxidase (GSH-Px), glutathione S transferase (GST) and glutathione reductase (GR) activities in erythrocytes and morning serum melatonin concentration in 14 healthy young adults and 14 healthy elderly people at baseline and after the 30th day of melatonin (5 mg daily) supplementation were determined. A significant age effect on increasing the MDA level and decreasing SOD-1, GSH-Px and GR activities as well as melatonin concentration was observed. Melatonin supplementation resulted in a significant increase in melatonin concentration, SOD-1 and GR activities and a decrease in the MDA level in both examined groups. These data indicate an age-related augmentation of oxidative stress in erythrocytes and the improvement of erythrocytic antioxidative defense by melatonin administration. These results might suggest melatonin supplementation to prevent age-related diseases and to prolong the lifespan and improve the quality of life of elderly people. PMID- 17286748 TI - Melatonin attenuates disruption of serum cholesterol status in rats with a single alpha-naphthylisothiocyanate treatment. AB - The present study was performed to examine whether melatonin attenuates disruption of serum cholesterol status in rats treated once with alpha naphthylisothiocyanate (ANIT). In the serum of rats treated with ANIT (75 mg/kg, i.p.), increases in total cholesterol, free cholesterol (F-Chol), low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and total bile acid concentrations and a decrease in the ratio of esterified cholesterol concentration to F-Chol concentration occurred 24 hr, but not 12 hr, after the treatment. In the liver of ANIT-treated rats, a decrease in cholesterol concentration and an increase in total bile acid concentration occurred 24 hr, after 12 hr, after the treatment. When melatonin (10 or 100 mg/kg, p.o.) was administered to ANIT-treated rats at 12 hr after the treatment, all these changes found in the serum and liver at 24 hr after the treatment were significantly attenuated at the higher dose. Melatonin (100 mg/kg) administered to ANIT untreated rats in the same manner increased the serum F-Chol and high-density lipoprotein cholesterol concentrations significantly. These results indicate that orally administered melatonin attenuates the disruption of serum cholesterol status in rats treated once with ANIT possibly by maintaining cholesterol metabolism and transport in the serum and liver. PMID- 17286749 TI - Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment. AB - The bipyridyl herbicide, diquat, is a potent prooxidant that generates superoxide anions through redox cycling in vivo. Exposure to elevated levels of this compound causes acute hepatic and renal toxicity as well as death in rodents. In the present study, we investigated whether melatonin, a free radical scavenger and antioxidant, could protect against diquat-induced hepatic and renal damage and whether the indole would improve survival of Kunming mice given a lethal dose of diquat. When mice were intraperitoneally (i.p.) given a single dose of diquat (50 mg/kg body weight), liver and kidney injuries were observed at 6 hr as indicated by elevated serum levels of both alanine aminotransferase (ALT) activity and blood urea nitrogen (BUN). In addition, lipid peroxidation levels in both liver and kidney showed significant increases as shown by elevated concentrations of F(2)-isoprostanes. The administration of melatonin (20 mg/kg) 30 min before the diquat injection resulted in a significant reduction in serum levels of ALT and BUN as well as hepatic and renal F(2)-isoprostanes levels. For the survival study, 75 mg/kg diquat was administered i.p. into mice to induce acute death. Without melatonin treatment, 10 of 23 (43.5%) mice died within 24 hr after diquat injection. Pretreatment with melatonin (20 mg/kg) 30 min prior to the injection of diquat and thereafter at 4-hr intervals until the end of the observation period (24 hr), reduced the death rate to two of 22 (9.1%) mice. Chi squared test revealed a significant difference with P < or = 0.05. In conclusion, melatonin, a broad spectrum antioxidant, reduces hepatic and renal damage and lowers the death rate in diquat-treated mice. PMID- 17286750 TI - Antiproliferative effects of melatonin on the growth of rat pituitary prolactin secreting tumor cells in vitro. AB - Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the growth of pituitary prolactin-secreting tumor cells. Primary cultured prolactinoma cells from E(2)-induced rat pituitary prolactin-secreting tumor were treated with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days. Apoptosis was evaluated using flow cytometry and the TdT-mediated dUTP nick-end labeling (TUNEL) method. In addition, cell viability was analyzed by (3,4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that incubation of prolactinoma cells with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days inhibited cell growth and increased cell apoptosis. Furthermore, melatonin increased caspase-3 activity, Bax mRNA expression, and cytochrome c protein expression. Conversely, Bcl-2 mRNA expression and mitochondrial membrane potential were inhibited by melatonin treatment. Our results further suggest that melatonin inhibits tumor growth by inducing apoptosis of rat pituitary prolactin secreting tumor directly via the damage of mitochondria. PMID- 17286751 TI - Melatonin increases stress fibers and focal adhesions in MDCK cells: participation of Rho-associated kinase and protein kinase C. AB - Melatonin cyclically modifies water transport measured as dome formation in MDCK cells. An optimal increase in water transport, concomitant with elevated stress fiber (SF) formation, occurs at nocturnal plasma melatonin concentrations (1 nm) after 6 hr of incubation. Blockage in melatonin-elicited dome formation was observed with protein kinase C (PKC) inhibitors. Despite, this information on the precise mechanism by which melatonin increases SF formation involved in water transport is not known. Focal adhesion contacts (FAC) are cytoskeletal structures, which participate in MDCK membrane polarization. SF organization and vinculin phosphorylation are involved in FAC assembly and both processes are mediated by PKC, an enzyme stimulated by melatonin; in these processes also involved is Rho-associated kinase (ROCK). Thus, we studied FAC formation and the ROCK/PKC pathway as the mechanism by which melatonin increases SF formation and water transport. The results showed that 1 nM melatonin and the PKC agonist phorbol-12-miristate-13-acetate increased FAC. The PKC inhibitor GF109203x, and the ROCK inhibitor Y27632, blocked increased FAC caused by melatonin. ROCK and PKC activities, vinculin phosphorylation and FAC formation were increased with melatonin. The PKC inhibitor, GF109203x, abolished both melatonin stimulated FAC in whole cells and ROCK activity, indicating that ROCK is a downstream kinase in the melatonin-stimulated PKC pathway in MDCK cultured cells that causes an increase in SF and FAC formation. Data also document that melatonin modulates water transport through modifications of the cytoskeletal structure. PMID- 17286752 TI - Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: implications for prostate cancer chemoprevention. AB - There is an unmet clinical demand for safe and effective pharmaceuticals/nutraceuticals for prostate cancer prevention and hormone refractory prostate cancer treatment. Previous laboratory and human studies of our laboratory demonstrated an association between the antiproliferative action of melatonin and melatonin MT(1) receptor expression in prostate cancer. The aim of this study was to determine, using a pharmacological approach, the signaling mechanisms of melatonin in hormone-refractory 22Rv1 human prostate cancer cell antiproliferation. Both immunoreactive MT(1) and MT(2) subtypes of G protein coupled melatonin receptor were expressed in 22Rv1 cells. Melatonin inhibited, concentration dependently, cell proliferation, upregulated p27(Kip1) gene transcription and protein expression, and downregulated activated androgen signaling in 22Rv1 cells. While the effects of melatonin were mimicked by 2 iodomelatonin, a high-affinity nonselective MT(1) and MT(2) receptor agonist, melatonin effects were blocked by luzindole, a nonselective MT(1) and MT(2) receptor antagonist, but were unaffected by 4-phenyl-2-propionamidotetraline, a selective MT(2) receptor antagonist. Importantly, we discovered that the antiproliferative effect of melatonin exerted via MT(1) receptor on p27(Kip1) gene and protein upregulation is mediated by a novel signaling mechanism involving co-activation of protein kinase C (PKC) and PKA in parallel. Moreover, we also showed that a melatonin/MT(1)/PKC mechanism is involved in melatonin induced downregulation of activated androgen signal transduction in 22Rv1 cells. Taken together with the known molecular mechanisms of prostate cancer progression and transition to androgen independence, our data provide strong support for melatonin to be a promising small-molecule useful for prostate cancer primary prevention and secondary prevention of the development and progression of hormone refractoriness. PMID- 17286753 TI - Melatonin is more effective than taurine and 5-hydroxytryptophan against hyperglycemia-induced kidney-cortex tubules injury. AB - The antioxidative effects of melatonin (Mel), 5-hydroxytryptophan (5-HTP) and taurine (TAU) on hyperglycemia-induced oxidative stress was investigated in primary cultures of kidney-cortex tubule cells grown in metabolically and hormonally defined medium. In the presence of 30 mm glucose (hyperglycemic conditions), cell viability was decreased by about 35% in comparison with that estimated in the glucose-depleted medium probably as a result of induction of apoptosis, as concluded from: (i) chromatin condensation and DNA fragmentation assays, (ii) a significant enhancement of reactive oxygen species (ROS) production, (iii) 8-hydroxydeoxyguanosine (8-OHdG) generation, (iv) an increased protein peroxidation and (v) a decline of reduced glutathione (GSH) levels leading to a disturbed glutathione redox state. The addition of 100 microm Mel to the hyperglycemic medium resulted in a twofold decrease in both 8-OHdG accumulation and protein peroxidation as well as restoration of the control intracellular ROS levels accompanied by a substantial increase in GSH/oxidized glutathione (GSSG) ratio due to a decline in GSSG content. ROS elimination was also achieved in the presence of 1 mm TAU which diminished protein and DNA injuries by about 25% and 30%, respectively. On the contrary, the action of 100 microm 5-HTP on ROS level, 8-OHdG generation, protein peroxidation and GSH/GSSG ratio was negligible. Thus, in contrast to 5-HTP and TAU, Mel might be considered as beneficial for diabetes therapy, particularly in terms of reduction of hyperglycemia-induced kidney injury. PMID- 17286754 TI - Safety considerations for the use of blue-light blocking glasses in shift workers. PMID- 17286756 TI - Clinical significance of autoantibodies recognizing Sjogren's syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sjogren's syndrome. AB - The aim of our study was (i) to compare the clinical and biological characteristics of 148 (137 women, 11 men) primary Sjogren's syndrome (pSS) patients at diagnosis as a function of their sex and (ii) to assess the prognostic value of anti-calpastatin and anti-alpha-fodrin autoantibodies. In addition, the presence of anti-nuclear antibodies (ANA), anti-52- and 60-kDa Sjogren's syndrome A (SSA), anti-Sjogren's syndrome B (SSB), anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factors (RF) of IgA, IgG and IgM isotypes was sought in sera collected at pSS onset. Raynaud's syndrome, significantly more frequent in women, was the only systemic manifestation of pSS whose frequency differed significantly as a function of the patient's sex (P = 0.02). ANA (P = 0.001) and anti-60-kDa SSA autoantibodies (P = 0.03) were significantly more common in women, while men never synthesized detectable levels of anti-SSB, anti-calpastatin or IgG anti-alpha-fodrin autoantibodies. In addition, anti-CCP autoantibodies were found in low percentages of pSS patients (4% F/18% M). The absence of autoantibodies does not exclude the diagnosis of pSS in men that will be based mainly on the anatomopathological findings of a minor salivary gland biopsy. Positivity of anti-60-kDa SSA, anti-SSB, anti-calpastatin, IgA and IgG anti-alpha-fodrin antibodies is not associated with pSS clinical and biological severity. PMID- 17286757 TI - Longitudinal changes in epitope recognition of autoantibodies against glutamate decarboxylase 65 (GAD65Ab) in prediabetic adults developing diabetes. AB - We analysed the beta cell-specific autoimmunity reflected in autoantibodies to the smaller isoform of glutamate decarboxylase (GAD65Ab) in the prediabetic period of GAD65Ab-positive healthy adults who developed Type 2 diabetes (T2D) during a follow-up period of 10 years. We found that of the adults that tested GAD65Ab-positive at baseline (n=25), six developed T2D and one developed Type 1 diabetes (T1D). Of the subjects that tested GAD65Ab-negative at baseline (n=2209), 81 developed T2D, one developed T1D and four developed unclassified diabetes, indicating that the risk for GAD65Ab-positive healthy adults to develop diabetes is increased sixfold. The GAD65Ab epitopes were characterized in a competition radioligand binding assay using recombinant Fab derived of GAD65 specific monoclonal antibodies. We observed that the GAD65Ab epitope specificities in the prediabetic period changed dynamically. Specifically, the binding to a middle and a C-terminal epitope increased during the follow-up period (P=0 x 03), causing a significant increase in the number of epitopes recognized (P=0 x 03). These findings are similar to previous observations of dynamic changes in the prediabetic period of schoolchildren at high risk for T1D development. However, the character of the epitopes differs between the two populations, suggesting differences in the beta cell-specific autoimmune response in the prediabetic period of patients with latent autoimmune diabetes in adults (LADA) and T1D. PMID- 17286758 TI - Ultraviolet B irradiation selectively increases the production of interleukin-8 in human cord blood-derived mast cells. AB - UVB irradiation modulates immune responses in the skin and is a major cause of sunburn, during which neutrophils accumulate in the skin. Because of their abundance in skin and ability to produce a variety of proinflammatory mediators, we propose that mast cells may play a key role in ultraviolet B (UVB)-induced skin inflammation. Cord blood-derived human mast cells were treated in vitro with varying doses of UVB and production of multiple cytokines was measured in culture supernatants. UVB exposure significantly increased the release of interleukin (IL)-8 and modestly increased IL-1alpha production, but cytokines such as IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma were unaffected. Cycloheximide reduced the UVB-mediated induction of IL-8 by 30-40%, suggesting that new protein synthesis contributed to IL-8 production. In line with this, UVB treatment of mast cells significantly increased IL-8 mRNA. In contrast to its effect on IL-8 production, optimal doses of UVB did not provoke histamine or tryptase release, indicating little effect on degranulation. Our data suggest that mast cells may play a major role during UVB induced acute inflammation by selectively inducing cytokines involved in neutrophil recruitment. PMID- 17286759 TI - Interleukin-6 expression and gene polymorphism are associated with severity of periodontal disease in a sample of Brazilian individuals. AB - Interleukin (IL)-6 is an inflammatory mediator involved in bone resorption. G/C polymorphism at position -174 of the IL-6 gene has been reported to influence IL 6 expression, with the G allele associated with higher expression levels. The aims of this study were to investigate the expression of IL-6 as well as the incidence of IL-6 (-174) gene polymorphism and their correlation to the severity of periodontitis in Brazilians. Peripheral blood mononuclear cells were collected from 12 non-smoker individuals with periodontitis for evaluation of IL-6 expression using flow cytometry. We observed a positive correlation between the mean clinical attachment loss and intensity of expression of IL-6, in which the greater the attachment loss, the higher the expression of IL-6 (P=0 x 007, R2=0 x 52). Also, patients with severe periodontitis displayed a higher intensity of IL 6 expression compared to moderate periodontitis (P=0 x 04). To determine the occurrence of IL-6 gene polymorphism, DNA was obtained from oral swabs of 209 Brazilian individuals with and without periodontitis. Polymerase chain reaction, restriction endonuclease digestion and electrophoresis were performed, allowing for detection of the IL-6 (-174) polymorphism. We observed that non-smokers with moderate periodontitis (P=0 x 05) and control (P=0 x 04) groups displayed a higher incidence of the G genotype when compared to severe periodontitis. This suggests that the G genotype may represent a protective role in severity of periodontitis. Thus, the increased expression of IL-6 and IL-6 (-174) polymorphism are associated with periodontal disease severity in Brazilian individuals. PMID- 17286760 TI - Increased CD11b expression on polymorphonuclear leucocytes and cytokine profiles in patients with Kawasaki disease. AB - Clinical evidence implicates polymorphonuclear leucocytes in the pathogenesis of vasculitis in Kawasaki disease. We examined modulation of expression of adhesion molecules (CD11b and CD62L) on polymorphonuclear leucocytes and how this expression is related to serum cytokine concentrations. In 18 patients with Kawasaki disease and 15 control subjects, adhesion molecule expression was determined by two-colour immunofluorescence staining of blood leucocytes and flow cytometry. Eight cytokines and chemokines were also measured. In patients with Kawasaki disease, mean fluorescence intensity for CD11b before giving intravenous immunoglobulin was significantly higher than in normal subjects (P<0 x 005). After intravenous immunoglobulin, mean fluorescence intensity for CD11b decreased significantly. With coronary artery lesions present, mean CD11b fluorescence intensity was significantly higher than without coronary artery lesions (P=0 x 005 before intravenous immunoglobulin; P=0 x 024 after intravenous immunoglobulin). No differences were seen in CD62L expression on polymorphonuclear leucocytes between patients with Kawasaki disease and normal subjects. CD11b expression on polymorphonuclear leucocytes correlated positively with serum interleukin (IL)-6, IL-10, granulocyte colony-stimulating factor, percentage of neutrophils among white cells and C-reactive protein. Polymorphonuclear leucocytes from patients with Kawasaki disease showed increased CD11b expression, which was associated with increased serum cytokines and appeared to be related to coronary artery lesions. PMID- 17286761 TI - Mannan-binding lectin is a determinant of survival in infective endocarditis. AB - Mannan-binding lectin (MBL) is a collectin plasma protein activating the lectin pathway of the complement system, enhancing opsonophagocytosis and modulating the cytokine response to inflammation. Deficiency of MBL, caused by structural mutations or promoter polymorphisms in the MBL2 gene, has been associated with increased susceptibility to infection and autoimmune disease. Thus, as infective endocarditis remains a severe disease requiring intensive and long-term treatment with antibiotics, we examined whether there was an association between MBL and clinical outcome in 39 well-characterized patients with infective endocarditis. Five patients (13%) had MBL concentrations < 100 microg/l and were considered MBL deficient. This proportion was similar to that in a healthy control group of blood donors. Mortality 3 months after diagnosis was 20% in patients with MBL deficiency and 9% in patients with normal MBL. The 5-year mortality was 80% and 25%, respectively. MBL-deficiency was on univariate survival statistics associated with significantly higher mortality on follow-up (P=0 x 03). In conclusion, this is the first report of an association between MBL-deficiency and survival in infective endocarditis. The present observation is important, as replacement therapy in MBL-deficient patients is possible. For certain high-risk subgroups, it opens new perspectives for improvement of treatment and outcome in infective endocarditis. PMID- 17286762 TI - Cutaneous and other lupus-like symptoms in carriers of X-linked chronic granulomatous disease: incidence and autoimmune serology. AB - The objective of this study was to determine the utility of anti-nuclear antibody (ANA) testing in the investigation of cutaneous and other lupus symptoms in female carriers of X-linked chronic granulomatous disease (CGD). We undertook a prospective study of 19 carrier mothers attending our institution, with direct questioning of carriers concerning symptoms and testing for anti-nuclear and anti phospholipid antibodies. A total of 58% reported significant photosensitive skin rashes, 42% reported mouth ulcers and 37% complained of joint pains that could not be attributed to other known causes. Anti-nuclear antibody (ANA) testing was negative in 73% of all carriers. The five positive ANAs were of low titre (maximum 1 : 320 on Hep 2 cells in two women) and only one weak positive double stranded DNA antibody and no extractable nuclear antibodies were found. Several of the mothers, despite negative serology, benefited from referral to a specialist, and in some cases to specific treatment. A history of skin rashes, joint pain, fatigue and mouth ulcers should be sought actively in the female relatives of X-CGD patients but negative lupus serology should not preclude referral to appropriate dermatology or rheumatology services. as symptoms may respond well to appropriate treatment. PMID- 17286763 TI - Pharmacovigilance studies in haemophilia. PMID- 17286764 TI - ReFacto and Advate: a single-dose, randomized, two-period crossover pharmacokinetics study in subjects with haemophilia A. AB - ReFacto is a recombinant B-domain-deleted, monoclonal antibody-purified, solvent detergent-treated factor VIII (BDDrFVIII) with no albumin added to the final formulation. Although ReFacto has been shown to be bioequivalent to a plasma derived FVIII product (Hemophil-M) in a randomized, crossover pharmacokinetic (PK) study, the comparability of ReFacto with the full-length (complete sequence) recombinant FVIII (FLrFVIII, Advate) product has not been previously examined in this manner. The primary objective of this study was to compare the PKs of ReFacto with those of Advate in patients with severe haemophilia A. This was a third-party unblinded, randomized, multicentre, two-period crossover PKs study of ReFacto and Advate in subjects with severe haemophilia A (FVIII:C < or =1%). Blood samples were collected over a 48-h period after i.v. administration of each of the FVIII products. FVIII:C was determined using the chromogenic substrate assay (CSA) in a central laboratory. The plasma FVIII:C PK parameters of ReFacto and Advate were determined using non-compartmental analysis. Bioequivalence was assessed on maximum plasma concentration (C(max)) and the area under the plasma concentration vs. time curves (AUCs) using an anova. The two products were judged to be equivalent if the 90% confidence limits of the ratio of the geometric mean values of C(max) and AUCs fell within the interval of 80-125%. Results from this PKs comparison of two different rFVIII products, using chromogenic substrate assay to measure FVIII:C, showed that ReFacto and Advate are bioequivalent to each other. PMID- 17286765 TI - Efficacy, safety and tolerability of recombinant factor VIII (REFACTO) in patients with haemophilia A: interim data from a postmarketing surveillance study in Germany and Austria. AB - An open-label, multicentre, postmarketing surveillance study conducted in Germany and Austria with recombinant factor VIII (REFACTO) has enrolled 217 patients (mean age 26.3 years) from 38 haemophilia centres during the first 4.8 years. Most patients (188/217; 86.6%) had severe to moderately severe haemophilia A, of whom 153 completed sufficient diary information for the main efficacy analysis. These 153 patients experienced a median of 6.6 (interquartile range 1.4-18.6) bleeding episodes per year. Patients treated with prophylaxis experienced a median of 4.4 (1.1-9.3) bleeds per year, while patients treated on-demand experienced a median of 22.8 (11.3-29.0) bleeds per year. Overall, most physicians (41/43 [95.3%]) were 'very satisfied' or 'satisfied' with the efficacy of REFACTO in the treatment of bleeding episodes. A total of 137 non-serious adverse events have been reported in 52/217 patients (24.0%) to date. In addition, 129 serious adverse events in 87 patients (40%) were reported, including 41 cases of 'less than expected therapeutic effect' (LETE). Of these, 39 LETE cases were reported in one centre; however, patients in this centre experienced considerably fewer bleeding episodes per year than patients outside this centre. Overall, six patients (2.8%) have developed de novo inhibitors, three of which were considered high titre. Four of these patients were at high risk (0-50 exposure days [ED]) of inhibitor formation, one was at intermediate risk (51-100 ED) and one was at low risk (>100 ED). These results emphasize the benefit of postmarketing surveillance and, overall, this study confirms the efficacy, safety and tolerability of REFACTO in the treatment of patients with haemophilia A. PMID- 17286766 TI - Efficacy and safety of a high purity, double virus inactivated factor VIII/von Willebrand factor concentrate (Biostate) in patients with von Willebrand disorder requiring invasive or surgical procedures. AB - Biostate is a double virally inactivated, plasma derived coagulation factor VIII (FVIII)/von Willebrand factor (VWF) concentrate registered and used in Australia, New Zealand and Asia for the treatment of patients with haemophilia A. Although Biostate has been well characterized for FVIII and VWF (ratio 1:2 respectively) and shows a similar VWF multimeric pattern to normal plasma, limited published data is available on its clinical efficacy and safety in patients with von Willebrand disorder (VWD) who require surgical procedures. We retrospectively assessed the efficacy and safety of Biostate in all VWD patients treated at three Australian haemophilia treatment centres undergoing invasive procedures or surgery over a 29-month period between April 2003 and September 2005. A chart review of 43 VWD patients (26 VWD type 1, 12 VWD type 2, 5 VWD type 3; 21 male, 22 female; mean age 52 years, range 19-80 years) undergoing 58 surgical procedures (24 major, 34 minor) was performed. For each procedure, data were collected on Biostate dosage and administration, adverse reactions, haemostatic efficacy and bleeding events. Haemostatic efficacy of Biostate was assessed as excellent in 78% or good in 22% of procedures. There were no bleeding events attributable to lack of efficacy in any patients. No adverse reactions related to the administration of Biostate were observed. These results suggest that Biostate is both safe and efficacious for the prevention of excessive bleeding in VWD patients undergoing surgery or invasive procedures. PMID- 17286768 TI - Hepatitis C virus genotypes among patients with thalassemia and inherited bleeding disorders in Markazi province, Iran. AB - Hepatitis C virus (HCV) genotypes, multiple genotypes infection and HCV seroprevalence were investigated among 98 thalassemia patients and 76 haemophiliacs in Markazi province, Iran. HCV antibody was detected in 5 (5.1%) of the first group and 33 (43.4%) of the latter. Risk factors associated with anti HCV antibody were also determined. Anti-HCV positivity in thalassemiacs were related to the number of blood transfusion units, splenectomy and duration of thalassemia. Analysis of risk factors in haemophiliacs revealed that seropositivity was significantly associated with duration of transfusion (P =0.009) and severity of disease (P = 0.000). The prevalence of HCV antibody in thalassemia subjects dropped from 8.1% to 0% after implementation of anti-HCV screening (1996). It was found that higher prevalence of HCV antibody in haemophiliacs (43.4%) compared with thalassemia patients (5.1%) correlated with clotting factor concentrates. Of the 34 seropositive haemophilia patients, HCV RNA was detected in 23 (67.7%). HCV genotype distribution was one in 50%, three in 18.2%, two in 4.54% and mixed in 27.3% (1 + 2 in 9.1%, 1 + 3 in 4.54%, 1 + 4 in 9.2% and 2 + 3a in 4.54%) cases. Among the five anti-HCV-positive thalassemiacs, two (40%) were positive for HCV RNA and one sample was found to be subtype 3a. This study confirms that multitransfused patients in Markazi province had similar genotype distribution as those previously reported form some other regions of Iran. Considering the possibilities of HCV mixed genotype among patients with haemophilia and thalassemia, accuracy and precision should be highly concerned in the detection of genotypes and their subsequent treatment. PMID- 17286767 TI - Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. AB - Recent reports have suggested that the incidence of inhibitors in haemophilia is the highest in those first exposed to factor VIII under 6 months of age. In this study, we investigated inhibitor development in children first exposed to FVIII as neonates and also examined the effect of other genetic and environmental variables. Three hundred and forty-eight children with severe haemophilia A were investigated. Inhibitors developed in 68 of 348 (20%), with 34 of 348 (10%) high titre inhibitors. The incidence in relation to initial FVIII exposure was: <1 month nine of 35 (26%), 1-6 months 13 of 51 (25%), 6-12 months 27 of 130 (21%), 12-18 months 13 of 66 (20%) and >18 months six of 66 (9%). While we observed a significant difference in inhibitor development and age at first exposure across all age groups (P = 0.018), no significant difference was observed in children treated at different time points during the first year of life (P = 0.44). Similar results were obtained for high titre inhibitors. There was also no difference in the incidence of inhibitors in relation to initial FVIII exposure in a subgroup of 144 children with the intron 22 mutation. Inhibitors developed more frequently in those initially treated with recombinant when compared with plasma-derived FVIII (P = 0.006) and in those with a major molecular defect (P = 0.009). In this study, exposure to FVIII during the neonatal period was not associated with a higher incidence of inhibitors than those treated later during the first year of life. Initial treatment with recombinant FVIII and the presence of a major molecular defect were the most important variables affecting inhibitor development. PMID- 17286769 TI - Percutaneous liver biopsy in adult haemophiliacs with hepatitis C virus: safety of outpatient procedure and impact of human immunodeficiency virus coinfection on the spectrum of liver disease. AB - Both HCV and HIV are common in haemophiliacs previously treated with non-viral inactivated clotting factor concentrates. Because of increased bleeding risks, little data are available on the safety of percutaneous outpatient liver biopsy (LBx) and impact of HIV coinfection in this population. This study aims at reporting our experience with percutaneous LBx in a cohort of haemophiliacs infected with HCV and describe the spectrum of disease and impact of HIV coinfection. A retrospective review of consecutive patients with haemophilia and HCV who underwent percutaneous LBx was performed. All patients were positive for HCV RNA by commercial assay and received factor concentrate prior to biopsy. A total of 29 male patients (mean age 36, 24 haemophilia A, five haemophilia B, and 44% coinfected with HIV) underwent successful outpatient percutaneous LBx without bleeding complication. Histologic activity index was 6.44 with advanced fibrosis (bridging fibrosis/cirrhosis) in 31%. When patients were stratified by HIV positive (n = 13) vs. HIV negative (n = 16), coinfected patients had higher fibrosis scores and higher proportion advanced fibrosis (54% vs. 12%; P = 0.0167) with no differences in age, demographic or other laboratory parameters. Multivariate logistic regression found that HIV positivity was independently associated with advanced fibrosis (OR = 3.7; 95% CI: 1.17-11.8; P = 0.026). Outpatient percutaneous LBx can be safely performed in patients with haemophilia. Despite similar age, HIV coinfection was an independent predictor of advanced fibrosis. These data support the hypothesis that HIV accelerates fibrosis progression in those coinfected with HCV and highlights the importance of liver histology in this population. PMID- 17286771 TI - Is primary postpartum haemorrhage a good predictor of inherited bleeding disorders? AB - A study was conducted to evaluate the value of screening for inherited bleeding disorders in women with primary postpartum haemorrhage (PPH). Over a 2-year period, women identified to have PPH (defined as >500 mL blood loss for spontaneous vaginal delivery, >700 mL for instrumental deliveries and >1000 mL for caesarean sections within 24 h of delivery) were invited to participate in this study testing for a possible underlying bleeding disorder at 3-9 months post delivery. Women known to have an inherited bleeding disorder were excluded. Of the 5744 deliveries in our unit during the study period, 152 (3%) fulfilled the criteria for primary PPH and 50 women agreed to participate in the study. Of these, 25 (50%) had a spontaneous vaginal delivery, 8 (16%) had an instrumental delivery and 17 (34%) had a caesarean section. Half of the women were multiparous and five (20%) had PPH in their previous pregnancy. Nineteen (38%) and 12 (24%) reported at least one significant personal and family bleeding history, respectively. One (2%) woman was identified to have von Willebrand disease. In conclusion, primary PPH does not appear to be a strong predictor of inherited bleeding disorders. Further studies are required to assess the prevalence of inherited bleeding disorders among these women. PMID- 17286770 TI - Robustness of factor assays following cordocentesis in the prenatal diagnosis of haemophilia and other bleeding disorders. AB - Prenatal diagnosis is the generally accepted option for genetic disorders including haemophilias and other bleeding disorders. Cord blood analysis between 17.4 and 20.6 weeks of gestation was performed in 172 confirmed carriers belonging to families of haemophilia A, haemophilia B, von Willebrand disease (VWD), factor VII and X deficiency; 133 were carriers for haemophilia A, 30 for haemophilia B, six for type 3 VWD, two for FX deficiency and one for FVII deficiency. The approach to the cord was either transabdominal or transamniotic. The volume of blood collected varied between 1 and 2 mL. In case of haemophilias, the diagnosis was offered by factor VIII/IX:C activity and antigen assays wherever required. In case of VWD, the diagnosis was based on von Willebrand factor antigen assays as detected by ELISA along with FVIII:C assay while in cases of FVII and FX deficiency, the diagnosis was based on FVII:C and FX:C respectively. The factor levels were compared with the normal range established in the laboratory for different coagulation factors between 18 and 21 weeks of gestation in women tested for other haematological disorders. Only in two cases, the procedure had to be repeated for reasons of extensive maternal contamination. All the deliveries have been followed up and the diagnoses reconfirmed by repeat clotting factor assays and DNA analysis whenever informative. Simple precautions like collection of fetal blood samples in smaller volumes in separate tubes, assaying multiple coagulation factors in the fetal blood samples helped us to offer diagnoses in all the women analysed. No fetal death or abortion was reported following the procedure. We suggest that accurate fetal blood sampling is a safe technique for the diagnosis of many of the bleeding disorders in places where genetic diagnostic services are not available. PMID- 17286772 TI - (32)P colloid radiosynovectomy in treatment of chronic haemophilic synovitis: Iran experience. AB - Repeated intra-articular bleeding with subsequent development of chronic synovitis and cartilage changes, leading to haemophilic arthropathy, is one the most debilitating problems in haemophilic patients. Radiosynovectomy is a familiar therapeutic choice in management of chronic synovitis in haemophilia. We report the treatments results of synoviorthesis with (32)P chromic phosphate with emphasis on clinical aspects. Between 2002 and 2006 we performed 66 procedures in 53 patients. Seven patients were excluded. The remaining 46 patients were followed for an average of 31 months. The mean age of patients at the time of injection was 15.9 years (range: 6-28). There were three repeat injections. According to Fernandez-pallazi and Cavilgia clinical classification (Table 1) [23], nine joints were Stage II and 46 were Stage III. In latest follow-up, 77% of patients reported at least a 50% decrease in bleeding frequency after treatment (P < 0.0001). The need for antihaemophilic factor consumption dropped by about 74% postradiosynovectomy (P < 0.0001). In most of the injected joints, the range of motion remained stable or improved. A trend was found for the number of haemarthrosis to increase after a period of considerable improvement. Synoviorthesis using (32)P effectively reduces the intra-articular bleeding rate and factor concentrate use. Durability of the response seems to be unpredictable, perhaps attributable to the late intervention. An early radiosynovectomy might be more helpful in terms of stability of response to treatment. PMID- 17286773 TI - Communicating about haemophilia within the family: the importance of context and of experience. AB - This study examines communication within families affected by haemophilia, focusing especially on communication about carrier status. A qualitative study using semi-structured interviews with family members in the UK revealed recurrent patterns in communication strategies and styles. Participants drew a marked contrast between the nature of communication within the clinic and within the home. In families, it is notable that communication usually occurs within the context of concrete experience of the condition. Noticeable differences existed in families with obligate carriers when compared with families with non-obligate carrier daughters. In families with affected sons, daughters may have more experience of haemophilia and consequently more understanding of their possible carrier status than in families with an affected father. Families also typically make value judgements and comments on coping strategies when they communicate about the condition. Readiness to receive information is very variable, and depends upon factors such as personality and life stage. Information may seem to be successfully communicated but the recipient may sometimes actually comprehend much less, only understanding more fully later or when the information becomes directly relevant to them. Periodic checking of understanding of different family members, and the provision of written information, may be helpful. PMID- 17286774 TI - Multicentric giant cell tumours in an adolescent with haemophilia. AB - ''Multicentric giant cell tumour (GCTs) of the extremity is prone to be distributed over the age range of 20-40 years, but is rare in haemophilia and in the age before 20. We report a case of a 15-year-old haemophilia boy who presented initially with two radiolucent loci in the right femur and tibia revealed from the X-ray films and then another lesion in the posterior femoral shaft shown from MRI by one year. Differential diagnosis of GCTs should be appraised in various aspects. Radiological diagnostic pitfall was avoided by the pathology disclosed GCTs without malignancy. The early diagnosis of GCTs in haemophilia may be delayed unless appearance of symptoms of pathologic fracture. Coincident multicentric GCTs do occur in haemophilic patients and their incidence might be underestimated, as it might not be judged because immediate symptoms of pain would resolve with appropriate factor replacement." PMID- 17286775 TI - Different clinical phenotype in triplets with haemophilia A. AB - Although many patients with haemophilia may have exactly the same residual clotting factor level, the clinical disease phenotype may vary greatly. This variation may be related to different genetic mutations responsible for haemophilia, environmental influences and co-inheritance of polymorphisms affecting the coagulation system. The study of siblings with haemophilia offers the opportunity to examine additional factors, other than genetic mutation and environment that may impact on the clinical phenotype of haemophilia. We present the unusual case of haemophilia occurring in fraternal triplets. Each of the triplets had a slightly different pattern of bleeding and response to treatment. PMID- 17286776 TI - Inhibitor development in one patient and laboratory discrepancies in several families with both mild haemophilia and Arg531Cys mutation. AB - Certain mutations in mild haemophilia A have been associated with a greater risk of inhibitor development, especially when associated with intense treatment. We present a patient with both mild haemophilia A and Arg531Cys mutation, which developed lowtitre inhibitors and was not seen to be related to the intense substitute treatment. The inhibitor has a greater effect on the exogenous factor VIII, permiting an adequate response to treatment with desmopressin. A discrepancy exists in the factor VIII activity in this our patient and in the haemophiliacs of another two families with the same mutation when determination is performed with one-stage or chromogenic method. PMID- 17286777 TI - Successful combination therapy of a proximal haemophilic pseudotumour with surgery, radiation and embolization in a child with mild haemophilia A. AB - We describe the management of a young boy with mild haemophilia A and a massive iliac pseudotumour with a multi modality approach involving factor replacement, radiation therapy, embolization and surgery. The patient was initially treated with recombinant factor VIII and radiation therapy. Because of inadequate response and worsening of bony erosion, the patient had a preoperative embolization followed by surgical excision. The surgical procedure was associated with minimal blood loss and the patient had a relatively smooth postoperative course with no physical morbidity. This case illustrates successful aggressive management of a large, proximally located pelvic pseudotumour, which resulted in an excellent outcome despite the need for a normally morbid operation. PMID- 17286778 TI - Factor VIII inhibitor associated with peginterferon--a follow up. PMID- 17286779 TI - Successful concurrent triple surgery in an adolescent patient with haemophilia A and inhibitors treated with recombinant factor VIIa. PMID- 17286780 TI - The haemophilic pseudotumour - surgical treatment by excision and filling the defect with calcium-phosphate cement granules. PMID- 17286781 TI - Molecular characterization of a novel mutation in the factor XIII A subunit gene associated with a severe defect and an adulthood diagnosis. PMID- 17286782 TI - The coagulation laboratory needs to move out of the middle age. PMID- 17286783 TI - Blastocystis hominis colitis in a haemophilic patient as a cause of lower gastrointestinal bleeding. PMID- 17286785 TI - Pharmacokinetics of quinine and its metabolites in pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria. AB - OBJECTIVES: The study was conducted in New Halfa teaching hospital, eastern Sudan to investigate the pharmacokinetics of quinine in pregnant Sudanese women. METHODS: Sixteen (eight pregnant and eight non-pregnant) Sudanese women infected with Plasmodium falciparum malaria were given a single dose of quinine hydrochloride (10 mg/kg body weight) as intravenous infusion over 2 h. The women were treated with intramuscular artemether. Plasma was collected before quinine administration and up to 72 h thereafter. These were analysed for quinine and its metabolites, 3-hydroxyquinine, (10R)-10,11-dihydroxyquinine and (10S)-10,11 dihydroxyquinine using high-performance liquid chromatography. RESULTS: The two groups were well matched in their basic characteristics. There was no significant difference in the mean maximum plasma concentration attained (C(max)), the mean time at which C(max) was attained, the elimination half-life (t(1/2)) and the total area under the plasma concentration vs. time curve (AUC) of quinine and its metabolites between the pregnant in non-pregnant women. CONCLUSION: There was no significant difference in quinine metabolism between pregnant and non-pregnant women and there is no need to adjust quinine dose when treating pregnant women. PMID- 17286786 TI - The impact of pharmacist-managed oral anticoagulation therapy in older veterans. AB - BACKGROUND: Older adults frequently have conditions requiring oral anticoagulation. Although clearly benefiting from oral anticoagulation, they are at increased risk for bleeding complications. Regular monitoring to optimize anticoagulation and to reduce the chance of major bleeding complications is required. The impact of oral anticoagulation monitoring by pharmacists in patients older than 75 years of age has not been described well. OBJECTIVE: To compare warfarin therapy prescribed and monitored by physicians to a pharmacist monitored anticoagulation service in a cohort of older veterans. METHODS: Retrospective chart review utilizing the Houston VA Medical Center's pharmacy database. Among all outpatients aged 75 years or older filling warfarin prescriptions between 1 March 2003 to 1 March 2005, and who were either monitored in a pharmacist's clinic or not, 103 patients per group were randomly selected. Information on demographics, indication for and length of warfarin therapy, INR values, and thromboembolic and bleeding events were abstracted. Differences were analysed using chi-squared test, Fisher's Exact test, and unpaired Student t test. RESULTS: A total of 1521 patients (440 in the pharmacist-monitored group, 1081 in the traditionally monitored group) met our inclusion criteria. One hundred and three patients per group were randomly selected for chart review. Although no significant difference in percentage of therapeutic INR values (48.1% pharmacist group, 46.4% conventional group) or in the incidence of major bleeding events was found, thromboembolic events occurred significantly less frequently in the pharmacist-monitored group (2 events vs. 12 events, P = 0.01). Minor bleeding events were more frequent in the pharmacist-monitored group (50 vs. 17, P < 0.01). However, time to follow-up after a sub- or supra-therapeutic INR was significantly shorter in the pharmacist monitored group (22 days vs. 68 days, and 14 days vs. 32 days, respectively). CONCLUSION: Pharmacist-monitored anticoagulation was associated with reduced thromboembolic events, an increase in minor bleeding events, and no difference in major bleeding events. Overall such monitoring by pharmacists should be recommended for older adults. PMID- 17286787 TI - Different effects of light food on pharmacokinetics and pharmacodynamics of three benzodiazepines, quazepam, nitrazepam and diazepam. AB - OBJECTIVE: Quazepam, nitrazepam and diazepam are administered under fed or fasted conditions for insomnia or anxiety disorder. Light bedtime food may have clinically relevant effects on the plasma levels of those drugs and hence on psychomotor performance. This study assessed the effect of light food on the pharmacokinetics and pharmacodynamics of these drugs. METHOD: Twenty-one eligible subjects were randomized to one of three groups of seven subjects: quazepam 20 mg, diazepam 5 mg or nitrazepam 5 mg. Each healthy subject took a single oral dose of the assigned drug after overnight fasting and after light food, on a separate occasion. Blood samples were collected until 72 h after dosing. The plasma samples were assayed using high-pressure liquid chromatography with spectrophotometric detection. Reaction time, critical flicker fusion test and visual analogue scales were conducted. RESULTS: The peak plasma concentration (C(max)) and area under the concentration-time curve (AUC) of quazepam with light food were 1.2-fold [90% confidence interval (CI): 1.1-1.5; P < 0.05] and 1.5-fold (90% CI: 1.3-1.9; P < 0.05) higher than that without light food, respectively. For nitrazepam and diazepam, the time to peak was delayed about 1 h in fed condition (P > 0.05). However it had no effect on their C(max) and AUC. Reaction time of quazepam with light food was prolonged at 4 and 6 h after dosing and its area under the effect-time curve from 0 to 10 h was increased (P < 0.05). CONCLUSION: Light food increased the bioavailability of quazepam and affected psychomotor performance. Light food delayed T(max) of nitrazepam and diazepam but had no effect on C(max) and AUC. PMID- 17286784 TI - Bevacizumab, a humanized anti-angiogenic monoclonal antibody for the treatment of colorectal cancer. AB - Angiogenesis is the process by which new blood vessels are created from pre existing vessels. It is essential for the growth and development of normal cells and tissues during embryonic and neonatal development and of tumour cells. Solid tumours rely on having an extensive network of blood vessels for growth and survival. The key mediator of angiogenesis, vascular endothelial growth factor-A (VEGF-A), is critical for the growth of tumours and their subsequent metastasis and is known to initiate angiogenesis. Bevacizumab is a humanized immunoglobulin G monoclonal antibody that binds to VEGF with high specificity, thereby blocking VEGF-mediated signalling pathways and thus angiogenesis. Clinical trials have shown that bevacizumab is effective in prolonging survival in patients with metastatic colorectal cancer (CRC) when combined with standard chemotherapy. Consequently, bevacizumab has been approved in combination with 5-fluorouracil based chemotherapy for first-line treatment of patients with metastatic CRC. Bevacizumab is generally well tolerated in most patients and does not exacerbate the adverse events associated with conventional chemotherapy. Bevacizumab-related side effects are generally manageable; however, monitoring for hypertension, gastrointestinal perforation, bleeding, proteinuria and thromboembolism is advised, especially in patients with predisposing factors. In addition to demonstrated survival benefits, the convenient dosing schedule and lack of interactions should ensure the successful integration of this novel agent into clinical practice. PMID- 17286789 TI - Nifedipine capsules may provide a viable alternative to oral powders for paediatric patients. AB - BACKGROUND AND OBJECTIVE: To compare content uniformities between different sizes of extemporaneously compounded nifedipine oral powders and capsules, in order to find out if capsules could be used instead of oral powders as paediatric medications. METHODS: Actual content and content uniformity of extemporaneously compounded 1-mg nifedipine oral powders and capsules were evaluated by a high performance liquid chromatographic assay. Capsules and powders were prepared by triturating 10-mg nifedipine tablets with different amounts of lactose or microcrystalline cellulose with a mortar and pestle using a standard geometric dilution technique. Oral powders were weighed individually and capsules were filled by a hand-operated capsule-filling machine. Four different sizes of powders (500, 300, 100 and 50 mg) and three different sizes of capsules (numbers 1, 3 and 4) were prepared. Ten oral powders and 10 capsules from each batch were randomly selected and individually assayed for nifedipine amount. RESULTS AND DISCUSSION: The extemporaneously prepared nifedipine oral powders and capsules were within acceptable limits for content uniformity, as defined by the European Pharmacopoeia, but the results indicate that the loss of nifedipine during the preparation process may be considerable for both preparations. The concentration on nifedipine decreased while the total mass of the oral powder decreased. These results demonstrate that nifedipine oral powders can be replaced by capsules, whose contents are emptied for use, in paediatric medications. Compounding small capsules, such as size number 3 or 4, is acceptable when considering the average drug content. The total weight of the oral powder should be at least 300 mg. CONCLUSION: The preparation of nifedipine in all studied capsule sizes was safe with either lactose monohydrate or microcrystalline cellulose as excipients. Thus, emptied capsules seem to be a good choice for delivering a paediatric medication. The loss of nifedipine was considerable in oral powders with low total weight. PMID- 17286788 TI - The effect of paclitaxel-loaded nanoparticles with radiation on hypoxic MCF-7 cells. AB - BACKGROUND AND OBJECTIVE: The inability of radiotherapy to eradicate completely certain human tumours may be due to the presence of resistant hypoxic cells. Several studies have confirmed the radiosensitizing effect of paclitaxel, a microtubular inhibitor. The object of this study was to evaluate the physicochemical characteristics of paclitaxel-loaded nanoparticles, and determine the ability of the released paclitaxel to radiosensitize hypoxic human breast carcinoma cells (MCF-7) with respect to radiation dose. METHODS: The poly(d,l lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. The morphology of the paclitaxel loaded nanoparticles was investigated by scanning electron microscopy. The drug encapsulation efficiency (EE) and in vitro release profile were measured by high performance liquid chromatography. Cell cycle was evaluated by flow cytometry. Cell viability was measured by the ability of single cells to form colonies in vitro. RESULTS: The prepared nanoparticles were spherical with diameter between 200 and 800 nm. The EE was 85.5%. The drug release pattern was biphasic with a fast release rate followed by a slow one. Co-culture of human breast carcinoma cells (MCF-7) with paclitaxel-loaded nanoparticles demonstrated that released paclitaxel retained its bioactivity to block cells in the G2/M phase of the cell cycle and effectively sensitized hypoxic MCF-7 cells to radiation with radiosensitivity shown to be dependent of radiation dose at levels of dosages studied. The sensitizer enhancement ratio for paclitaxe-loaded nanoparticles at 10% survival is approximately 1.4. CONCLUSION: This work has demonstrated that paclitaxel can be effectively released from a biodegradable PLGA nanoparticle delivery system while maintaining potent combined cytotoxic and radiosensitizing abilities for hypoxic tumour cells. PMID- 17286790 TI - Applications of population pharmacokinetics in current drug labelling. AB - BACKGROUND AND OBJECTIVE: The application of population pharmacokinetics (PopPK) appears increasingly in drug labelling. The current study was to examine the use of PopPK in dose recommendation in drug-product labels. METHOD: PopPK information was identified in the data sheets included in the physician desk reference (PDR). Electronic key word searches were conducted in the electronic library of PDR. The use of PopPK in the prescribing information, including the determination of dosing regimen, dosing in special populations and dose-adjustments was summarized and evaluated. The reliability and criteria for integrating the information derived from PopPK studies into the product labelling were discussed. RESULTS AND DISCUSSION: Among more than 2500 items listed in the PDR, 88 listings were found to have PopPK information in the labelling. The information included general data (Gen) on pharmacokinetics (PK) and the effects of gender (sex), age, race, drug drug interactions (DDI), smoking (Smk), alcohol consumption (Alc), disease state (Dis), renal impairment (Ren) and metabolic status (Met) on the PK parameters (Table). Whether there was an effect (+) or not (-) is also shown. Appendix 1 lists the products included in each category. Searches conducted at different times suggest an increase in both quantity and quality of PopPK data in drug development. PopPK is widely used in paediatric studies and the sample sizes in these studies are sometimes too small. The application of PopPK to protein drugs is increasing rapidly (Appendix 2). Several precautions should be exercised when PopPK is applied to protein drugs. When considering gender effects, different normalization methods for body weight have been used. The number of subjects included in the PopPK analysis should be given and the influence of the imbalance in any covariate should be investigated. PopPK-DDI results are particularly difficult to evaluate unless details about potentially influential factors such as dosing and sampling information for both drug and interacting drugs are given. CONCLUSIONS: The use of PopPK to aid optimal dosing is increasing. Several noticeable problems raised usually avoid the acceptability of PopPK studies. More investigations are needed to inform the development of consensuses on these issues. There is an accelerating shift from PopPK to PopPK/PD. The limitations of such modelling should be recognized. PMID- 17286791 TI - Development of an intelligent decision support system for medication review. AB - BACKGROUND AND OBJECTIVE: The aim was to develop and evaluate a pilot version of a knowledge-based system that can identify existing and potential medication related problems from patient information. This intelligent system could directly support pharmacists and other health professionals providing medication reviews. METHODS: Rather than being based on static rules to trigger alerts, this system utilizes a multiple classification ripple-down rules approach, which allows the user to build rules incrementally and improve the accuracy of the knowledge base in identifying medication-related problems while the system is in use, with no outside assistance or training. The system contextualizes the potential drug therapy problems by taking into consideration the patient's demographics, and other medical condition and drugs. The system is capable of both being instructed in the domain of medication review through its routine use by an expert, and acting similarly to the expert when analysing genuine medication review cases. The system was handed over to an experienced clinical pharmacist (expert), with no knowledge or conclusions preloaded into the system. The expert was then able to add the case details and generate the rules required for 126 actual medication review cases. RESULTS: Over 250 rules were generated from the review cases, incorporating demographics, medical history, symptoms, medications and pathology results from these cases. At the completion of the cases, more than 80% of the potential medication-related problems identified by the expert were also detected by the system. The false positive rate, or number of incorrect medication-related problems identified by the system, was <10% overall and was zero for the last 15 cases analysed. The system found significantly more potential medication-related problems than the expert, with the system consistently remaining at least one finding ahead. There was a high incidence of missed potential medication-related problems by the expert, which were automatically repaired by the system. CONCLUSIONS: The knowledge-based system has already demonstrated that the technique employed is well suited to a domain of this nature and has furthermore demonstrated that it is capable of improving the quality of service that the medication reviewer can provide. The system will be further enhanced and tested prior to use in the field. It should help pharmacists in the provision of medication reviews, improving their clinical and time management capabilities, and enhancing their ability to contribute to the quality use of medications. PMID- 17286792 TI - Genetic polymorphisms in MDR1 and CYP3A5 and MDR1 haplotype in mainland Chinese Han, Uygur and Kazakh ethnic groups. AB - BACKGROUND AND OBJECTIVE: The drug transporter MDR1 and the drug metabolizing enzyme CYP3A are the two major biological factors determining the pharmacokinetics of many drugs. The functional MDR1 single nucleotide polymorphisms (SNPs) and a prevalent CYP3A5 SNP show marked interethnic variation among Orientals, Caucasians and Africans. In this study, we investigated the distribution of MDR1 and CYP3A5 SNPs among mainland Chinese Han, Uygur and Kazakh ethnic groups. METHODS: Genotypes of the MDR1 C1236T, G2677T/A and C3435T, and CYP3A5*3, CYP3AP1*3 SNPs were determined in 434 unrelated healthy subjects (165 Chinese Han, 161 Chinese Uygur and 108 Chinese Kazakh) using polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS AND DISCUSSION: A significantly higher MDR1 3435T variant frequency was observed in Uygur (52.8%), than in Kazakh (39.8%) and Han (37.9%) Chinese (P < 0.01, Fisher's exact test). There was no significant difference in MDR1 1236T and 2677T/A variant frequencies between Han, Uygur and Kazakh. CYP3A5*3 (G) allele was observed at intermediate frequencies in Uygur (84.8%) and Kazakh (86.6%), relative to Han (72.7%) and values previously reported in Caucasians (91.7%). The CYP3AP1*3 (A) allele was strongly linked to CYP3A5*3 in Chinese Han, Uygur and Kazakh. CONCLUSION: Significant interethnic differences in MDR1 haplotype and CYP3A5 variant frequencies exist between mainland Chinese Han and Caucasians, and the intermediate frequencies observed in Chinese Uygur and Kazakh might be due to the genetic admixture of Eurasians and Orientals. PMID- 17286793 TI - Amisulpride augmentation after the failure of citalopram for depression: a case report. AB - This case report describes a 35-year-old woman with a first depressive episode. She was treated with the serotonergic antidepressant citalopram for 12 weeks without therapeutic response. Low-dose amisulpride augmentation resulted in a significant clinical improvement. We hypothesize that the dopaminergic properties of amisulpride might augment the effects of serotonergic antidepressants in refractory patients. PMID- 17286794 TI - Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine-zinc): a case of decompensated liver cirrhosis in Wilson's disease. AB - OBJECTIVES: To report a case of early-decompensated liver cirrhosis secondary to discontinuation of penicillamine therapy in a patient with Wilson's disease. CASE SUMMARY: A 33-year-old Chinese female patient was diagnosed with Wilson's disease, for which penicillamine 250 mg p.o. once daily was prescribed. However, the patient developed intolerance and penicillamine was discontinued without alternative treatment. Five months later, she developed decompensated liver cirrhosis with hepatic encephalopathy. Eventually, the patient died because of the complications of sepsis and decompensated liver failure. DISCUSSION: Chelating agent is the mainstay of treatment in Wilson's disease, which is an inherited disorder of hepatic copper metabolism. Therapy must be instituted and continued for life once diagnosis is confirmed. Interruption of therapy can be fatal or cause irreversible relapse. Penicillamine given orally is the chelating agent of first choice. However, its unfavourable side-effects profile leads to discontinuation of therapy in 20-30% of patients. In most case reports, cessation of penicillamine without replacement treatment causes rapid progression to fulminant hepatitis, which is fatal unless liver transplantation is performed. CONCLUSION: In this, we highlight a case of discontinuation of penicillamine in a patient with Wilson's disease without substitution with alternative regimen. This was caused by unavailability of the alternative agents such as trientine in our country. Consequently, the patient progressed to decompensated liver cirrhosis with encephalopathy and eventually passed-away within 5 months. One recent study supports a combination of trientine and zinc in treating patient with decompensated liver cirrhosis. This combination is capable of reversing liver failure and prevents the need of liver transplantation. Both trientine and zinc are not registered in Malaysia. Therefore, liver transplantation was probably the only treatment option for this patient. Hence, non-availability of orphan drugs in clinical practice is certainly a subject of serious concern. Systems for better management of patients with rare diseases need to be instituted by all the institutions concerned. PMID- 17286795 TI - Alternate venlafaxine kinetics in overdose patients. PMID- 17286796 TI - Msp2 variation in Anaplasma phagocytophilum in vivo does not stimulate T cell immune responses or interferon-gamma production. AB - Msp2 is Anaplasma phagocytophilum's immunodominant protein. Antigenic variability with msp2 gene conversion may drive differential immunopathology with infection by bacteria of different in vitro passage intervals. We examined msp2 transcript variation and its relationship to histopathology, T-cell and antibody responses in mice infected with differentially passaged A. phagocytophilum. Hepatic inflammation peaked on day 2-4 with low passage bacteria and on day 4-7 with high passage bacteria infection. Nineteen msp2 variant transcripts were identified. The low and high passage inocula shared four, but differed in one and two msp2 transcript variants, respectively. After infection, three and two msp2 variants were only identified in low or high passage infected mice. However, per mouse, msp2 variant profiles were unique with no evident expression program. In low and high passage bacteria-infected mice, splenocytes proliferated to whole A. phagocytophilum at day 7-10, diminishing thereafter. Weak mitogenic responses to whole bacteria were detected in mock and infected mice at d0 and sporadically thereafter. Essentially no lymphoproliferation or IFN-gamma production resulted from stimulation by six Msp2 hypervariable region proteins, although antibodies were detected to all, including cross-reactions. Differential A. phagocytophilum Msp2 expression is unrelated to T-cell response and unlikely to induce the cellular immunopathology underlying disease manifestations. PMID- 17286798 TI - The C-terminus of pokeweed antiviral protein has distinct roles in transport to the cytosol, ribosome depurination and cytotoxicity. AB - Pokeweed antiviral protein (PAP) produced by pokeweed plants is a single-chain (type I) ribosome-inactivating protein (RIP) that depurinates ribosomes at the alpha-sarcin/ricin loop of the large rRNA, resulting in inhibition of translation. Unlike the type II RIPs, which have an active and a binding moiety, PAP has only the active moiety. The mechanism by which toxins without a binding moiety gain access to cytosolic ribosomes is not known. We set up yeast as a simple and genetically tractable system to investigate how PAP accesses ribosomes and showed that the mature form of PAP is targeted to the cytosol from the endomembrane system in yeast. In the present study, we performed a systematic deletion analysis to identify the signal required for transport of PAP to the cytosol. We demonstrate here that processing of the C-terminal extension and sequences at the C-terminus of the mature protein are critical for its accumulation in the cytosol. Using a series of PAP mutants, we identified the C terminal signal and demonstrated that it is distinct from the sequences required for ribosome depurination and cytotoxicity. The C-terminal motif showed sequence similarity to type II RIPs that retrotranslocate from the endoplasmic reticulum to the cytosol. These results demonstrate that a conserved sequence at the C terminus of a type I RIP mediates its transport to the cytosol and suggest that type I and II RIPs may use a common signal to enter the cytosol. PMID- 17286797 TI - Sugar-inducible expression of the nucleolin-1 gene of Arabidopsis thaliana and its role in ribosome synthesis, growth and development. AB - Animal and yeast nucleolin function as global regulators of ribosome synthesis, and their expression is tightly linked to cell proliferation. Although Arabidopsis contains two genes for nucleolin, AtNuc-L1 is the predominant if not only form of the protein found in most tissues, and GFP-AtNuc-L1 fusion proteins were targeted to the nucleolus. Expression of AtNuc-L1 was strongly induced by sucrose or glucose but not by non-metabolizable mannitol or 2-deoxyglucose. Sucrose also caused enhanced expression of genes for subunits of C/D and H/ACA small nucleolar ribonucleoproteins, as well as a large number of genes for ribosomal proteins (RPs), suggesting that carbohydrate availability regulates de novo ribosome synthesis. In sugar-starved cells, induction of AtNuc-L1 occurred with 10 mM glucose, which seemed to be a prerequisite for resumption of growth. Disruption of AtNuc-L1 caused an increased steady-state level of pre-rRNA relative to mature 25S rRNA, and resulted in various phenotypes that overlap those reported for several RP gene mutants, including a reduced growth rate, prolonged lifetime, bushy growth, pointed leaf, and defective vascular patterns and pod development. These results suggest that the rate of ribosome synthesis in the meristem has a strong impact not only on the growth but also the structure of plants. The AtNuc-L1 disruptant exhibited significantly reduced sugar-induced expression of RP genes, suggesting that AtNuc-L1 is involved in the sugar inducible expression of RP genes. PMID- 17286799 TI - Affinity maturation of immunoglobulin A anti-tissue transglutaminase autoantibodies during development of coeliac disease. AB - Coeliac disease (CD) is an immune-mediated enteropathy triggered by ingestion of wheat gluten and related cereals in genetically predisposed individuals. Circulating immunoglobulin A (IgA) class autoantibodies against tissue transglutaminase (IgA-TGA) are highly specific and sensitive serological markers for CD, which is ultimately confirmed by duodenal biopsy. Although CD is considered a life-long disorder, transient or fluctuating IgA-TGA seropositivity has been observed in asymptomatic individuals on a gluten-containing diet. We set out to explore possible differences in the maturation of IgA-TGA avidity between individuals progressing to CD and subjects remaining healthy despite occasional expression of autoantibodies. We developed a time-resolved fluorometric IgA-TGA assay based on human recombinant tissue transglutaminase (tTG), and further modified the method to also measure urea-dependent avidity of the autoantibodies. We measured the autoantibody titres and avidities of sequential serum samples from 10 children developing CD and 10 children presenting transient or fluctuating autoantibodies. Both the initial titres at seroconversion and peak values of transient/fluctuating IgA-TGA were significantly lower than corresponding autoantibody titres in samples drawn from individuals with progressing CD (P = 0.004 and P = 0.0002, respectively). However, there were no statistically significant differences in the initial or peak avidity index values between the two groups of children. The avidity index values increased during the follow-up period (P = 0.013 for both groups) with no significant difference in the rate of avidity maturation between children with transient/fluctuating IgA TGA and children developing CD. According to our results, high autoantibody titres have a higher predictive value than avidity maturation of TGA-IgA in screening for CD. PMID- 17286800 TI - Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. AB - The mechanism of action of methotrexate (MTX) in autoimmune diseases (AID) is unclear. A pro-apoptotic effect has been demonstrated in mitogen-stimulated peripheral blood mononuclear cells (PBMC), but studies employing conventional antigens have disputed a pro-apoptotic effect. CD4+ T helper (Th) cells play a significant role in most AID. We therefore examined directly, by flow cytometry, the uptake of MTX by the T helper (Th) cells stimulated for 6 days with Candida albicans (CA) or tetanus toxoid (TT), and its consequences with respect to induction of apoptosis. While none of the resting Th cells took up MTX, nearly all the dividing Th cells did, and this abrogated further cell division. Among dividing Th cells, MTX induced an approximately sixfold increase over baseline levels in the proportion of apoptotic cells. This proportion could be reverted to baseline by the addition of folic acid. Exposure of CA-stimulated PBMC to MTX significantly increased their level of cleaved poly(ADP-ribose) polymerase (PARP), and a similar tendency was observed in TT-stimulated cells. Unlike CA and TT, the mitogen phytohaemagglutinin (PHA) induced proliferation of both CD4- and CD4+ T cells, and induced apoptosis in both undivided and divided Th cells. PHA induced apoptosis involved activation of caspase-3 and the anti-apoptotic protein Bcl-2 in addition to PARP cleavage, suggesting that PHA induces apoptosis via different pathways than CA and TT. We suggest that the latter are more representative of stimulation with self-antigens in AID, and that a pro-apoptotic effect of MTX on self-antigen-stimulated Th cells contributes to the effect of MTX in the treatment of AID. PMID- 17286801 TI - Different temporal expression of immunodominant Ro60/60 kDa-SSA and La/SSB apotopes. AB - Opsonization of apoptotic cardiocytes by maternal anti-Ro/SSA and anti-La/SSB antibodies contributes to tissue injury in the neonatal lupus syndrome. The objective of the current study was to quantify the surface membrane expression of Ro/La components during different phases of apoptosis and map the Ro/La apotopes (epitopes expressed on apoptotic cells) bound by cognate antibodies. Multi parameter flow cytometry was used to define early and late apoptotic populations and their respective binding by monospecific anti-Ro and anti-La IgGs. Anti-Ro60 bound specifically to early apoptotic Jurkat cells and remained accessible on the cell surface throughout early and late apoptosis. In contrast, anti-La bound exclusively to late apoptotic cells in experiments controlled for non-specific membrane leakage of IgG. Ro52 was not accessible for antibody binding on either apoptotic population. The immunodominant NH2-terminal and RNA recognition motif (RRM) epitopes of La were expressed as apotopes on late apoptotic cells, confirming recent in vivo findings. An immunodominant internal epitope of Ro60 that contains the RRM, and is recognized by a majority of sera from mothers of children with congenital heart block (CHB) and patients with primary Sjogren's syndrome, was also accessible as an apotope on early apoptotic cells. The distinct temporal expression of the immunodominant Ro60 and La apotopes indicates that these intracellular autoantigens translocate independently to the cell surface, and supports a model in which maternal antibody populations against both Ro60 and La apotopes act in an additive fashion to increase the risk of tissue damage in CHB. PMID- 17286803 TI - C-terminal prenylation of the CLN3 membrane glycoprotein is required for efficient endosomal sorting to lysosomes. AB - Mutations in the polytopic lysosomal membrane glycoprotein CLN3 result in a severe neurodegenerative disorder. Previous studies identified two cytosolic signal structures contributing to lysosomal targeting. We now examined the role of glycosylation and the C-terminal CAAX motif in lysosomal transport of CLN3 in non-neuronal and neuronal cells. Mutational analysis revealed that in COS7 cells, CLN3 is glycosylated at asparagine residues 71 and 85. Both partially and non glycosylated CLN3 were transported correctly to lysosomes. Mevalonate incorporation and farnesyltransferase inhibitor studies indicate that CLN3 is prenylated most likely at cysteine 435. Substitution of cysteine 435 reduced the steady-state level of CLN3 in lysosomes most likely because of impaired sorting in early endosomal structures, particularly in neuronal cells. Additionally, the cell surface expression of CLN3 was increased in the presence of farnesyltransferase inhibitors. Alteration of the spacing between the transmembrane domain and the CAAX motif or the substitution of the entire C terminal domain of CLN3 with cytoplasmic tails of mannose 6-phosphate receptors have demonstrated the importance of the C-terminal domain of proper length and composition for exit of the endoplasmic reticulum. The data suggest that co operative signal structures in different cytoplasmic domains of CLN3 are required for efficient sorting and for transport to the lysosome. PMID- 17286804 TI - Meeting report--Imaging membrane dynamics, 14-17 September, Royal Holloway- University of London, UK. PMID- 17286802 TI - Bronchoalveolar neutrophils, interferon gamma-inducible protein 10 and interleukin-7 in AIDS-associated tuberculosis. AB - During advanced AIDS tuberculosis (TB) often presents atypically with smear negative and non-cavitary disease, yet immune features associated with this change are poorly characterized. We examined the local immune response in a cohort of Tanzanian AIDS-associated TB patients who underwent bronchoalveolar lavage. TB infection was confirmed in bronchoalveolar lavage (BAL) fluid by culture, probe and polymerase chain reaction (PCR). Among TB patients CD4 count correlated positively with the extent of cavitary disease as well as BAL TB load (qPCR C(T)). TB patients had significantly higher granulocyte-macrophage colony stimulating factor (GM-CSF) than non-TB patients, and those with non-cavitary TB had significantly higher BAL interferon gamma-inducible protein (IP-10) and interleukin (IL)-7 than those with cavities. BAL neutrophils were as prevalent as monocytes/macrophages or epithelial cells, and immunohistochemistry revealed that neutrophils, monocytes/macrophages, and epithelial cells were major sources of the IP-10 and IL-7. These data suggest a dysregulated cytokine profile may contribute to the TB of advanced AIDS. PMID- 17286806 TI - Epidermal keratinocytes as the forefront of the sensory system. AB - Various sensors that respond to physical or chemical environmental factors have been identified in the peripheral nervous system. Some of them, which respond to mechanical stress, osmotic pressure, temperature and chemical stimuli (such as pH), are also expressed in epidermal keratinocytes. Neurotransmitters and their receptors, as well as receptors that regulate the neuroendocrine system of the skin, are also present in keratinocytes. Thus, broadly speaking, epidermal keratinocytes appear to be equipped with sensing systems similar to those of the peripheral and central nervous systems. It had long been considered that only nerve C-terminals in the epidermis play a role in skin surface perception. However, building on earlier work on skin receptors and new findings introduced here, we present in this review a novel hypothesis of skin sensory perception, i.e. first, keratinocytes recognize various environmental factors, and then the information is processed and conveyed to the nervous system. PMID- 17286805 TI - Nucleocytoplasmic trafficking is required for functioning of the adaptor protein Sla1p in endocytosis. AB - Dual localization of proteins at the plasma membrane and within the nucleus has been reported in mammalian cells. Among these proteins are those involved in cell adhesion structures and in clathrin-mediated endocytosis. In the case of endocytic proteins, trafficking to the nucleus is not known to play a role in their endocytic function. Here, we show localization of the yeast endocytic adaptor protein Sla1p to the nucleus as well as to the cell cortex and we demonstrate the importance of specific regions of Sla1p for this nuclear localization. A role for specific karyopherins (importins and exportins) in Sla1p nuclear localization is revealed. Furthermore, endocytosis of Sla1p-dependent cargo is defective in three strains with karyopherin mutations. Finally, we investigate possible functions for nuclear trafficking of endocytic proteins. Our data reveal for the first time that nuclear transport of endocytic proteins is important for functional endocytosis in Saccharomyces cerevisiae. We determine the mechanism, involving an alpha/beta importin pair, that facilitates uptake of Sla1p and demonstrate that nuclear transport is required for the functioning of Sla1p during endocytosis. PMID- 17286807 TI - Immunohistochemistry and in situ hybridization in the study of human skin melanocytes. AB - Although keratinocytes are the most numerous type of cell in the skin, melanocytes are also key players as they produce and distribute melanin that protects the skin from ultraviolet (UV) radiation. In vitro experiments on melanocytic cell lines are useful to study melanogenesis and their progression towards melanoma. However, interactions of melanocytes with keratinocytes and with other types of cells in the skin, such as fibroblasts and Langerhans cells, are also crucial. We describe two techniques, immunohistochemistry (IHC) and tissue in situ hybridization (TISH), that can be used to identify and study melanocytes in the skin and their responses to UV or other stimuli in situ. We describe a practical method to localize melanocytic antigens on formalin-fixed, paraffin-embedded tissue sections and in frozen sections using indirect immunofluorescence with conjugated secondary antibodies. In addition, we detail the use of TISH and its combination with IHC to study mRNA levels of genes expressed in the skin at cellular resolution. This methodology, along with relevant tips and troubleshooting items, are important tools to identify and study melanocytes in the skin. PMID- 17286808 TI - Oxymetazoline modulates proinflammatory cytokines and the T-cell stimulatory capacity of dendritic cells. AB - The nasal decongestant oxymetazoline (OMZ) is frequently used in the topical treatment of rhinitis/sinusitis. As proinflammatory cytokines play a critical role in the development and maintenance of local inflammation, the aim of this study was to investigate the influence of OMZ on immune cells in order to diminish the mucosal infiltration of the nose. Peripheral blood mononuclear cells (PBMC) from buffy coats of healthy volunteers were isolated and stimulated in the presence or absence of OMZ. In addition, monocyte-derived dendritic cells (DC) were generated and different concentrations of OMZ were added. DC phenotype and their T-cell stimulatory properties were analysed. The vasoactive substance OMZ showed a concentration dependent inhibitory effect on T-cell activation as well as a dominant effect on T-cell stimulatory properties of DC. Low concentrations of OMZ inhibited the proliferation of polyclonally activated T cells. In addition, secretion of proinflammatory mediators such as the cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF alpha), IL-6 and IL-8 were inhibited in the presence of physiological doses of OMZ. Interestingly, the addition of IL-6 to DC-T-cell co-culture was able to completely restore T cell proliferation. In conclusion, these findings indicate that the anti inflammatory properties of OMZ are partially mediated by the inhibition of proinflammatory cytokines as well as reduced T-cell stimulatory capacity of DC resulting in a repressed stimulation of T cells. Therefore, the therapeutic benefit of OMZ can be explained in part by its immunomodulating effects in the topical treatment of nasal inflammation. PMID- 17286809 TI - Expression patterns of programmed cell death 4 protein in normal human skin and some representative skin lesions. AB - Expression of a tumor suppressor gene, programmed cell death 4 (PDCD4), was investigated at the protein level in the human skin. Immunohistochemically, PDCD4 protein expressed mainly in suprabasal layers, while PDCD4-positive and -negative areas were observed discontinuously in the basal cell layer of the epidermis. In hair follicles, the suprabulbar area including the hair and inner root sheath was immunoreactive, while the bulbar area, containing germinative cells which were strongly proliferating cell nuclear antigen (PCNA)-positive, was not or less. PDCD4 therefore appears to be important in the differentiation of hair follicles. PDCD4-positive cells were localized in the inside layers while PCNA-positive cells were located in the basal layer in the outer root sheath of hair follicles. The cells of sebaceous glands and sweat glands also were PDCD4-positive. The PDCD4 protein was localized mostly in nuclei of cutaneous cells. PDCD4 expression was found to be suppressed in the epidermis overlying an adult T-cell lymphoma (ATL), possibly reflecting a paracrine effect of factors produced by ATL cells. PDCD4 expression was suppressed in the keratinocyte cell line HaCaT by exposure of cultures to epidermal growth factor, transforming growth factor-beta1 or hepatocyte growth factor. Immunohistochemically, various skin cancers tended to show less PDCD4 expression than normal skin. Promotion of expression might prove useful in preventing or treating certain skin cancers. PMID- 17286810 TI - Rapid, high-quality and epidermal-specific isolation of RNA from human skin. AB - As global transcriptome analyses with a growing demand on layer-specific applications are widely used in cutaneous biology, we investigated the effect of established and optimized dermo-epidermal separation methods on the quality of RNA. We compared enzymatic separation with dispase, chemical separation with 1 M sodium chloride and heat separation to a treatment with 3.8% ammonium thioyanate. The impact of freezing as well as the addition of 10 mM aurintricarboxylic acid was considered in the evaluation of the amount and quality of isolated RNA from dermis and epidermis. Using the low abundant gene kallikrein 12 for real-time PCR analysis, we were able to demonstrate the superior RNA quality after dermo epidermal separation using 3.8% ammonium thiocyanate. In addition to the time effectiveness this separation technique promises dermal and epidermal purity and is therefore the method of choice for producing high-quality RNA for genome-wide dermal and epidermal transcriptional analysis. PMID- 17286813 TI - Cutting-edge international tree research in New Phytologist. PMID- 17286814 TI - Towards a rhizo-centric view of plant-microbial feedbacks under elevated atmospheric CO2. PMID- 17286815 TI - From the inside out: fungal endophyte-grass associations and grassland communities. PMID- 17286816 TI - A diversity of scales. PMID- 17286817 TI - Towards forest community and ecosystem genomics. PMID- 17286818 TI - Zinc in plants. AB - Zinc (Zn) is an essential component of thousands of proteins in plants, although it is toxic in excess. In this review, the dominant fluxes of Zn in the soil-root shoot continuum are described, including Zn inputs to soils, the plant availability of soluble Zn(2+) at the root surface, and plant uptake and accumulation of Zn. Knowledge of these fluxes can inform agronomic and genetic strategies to address the widespread problem of Zn-limited crop growth. Substantial within-species genetic variation in Zn composition is being used to alleviate human dietary Zn deficiencies through biofortification. Intriguingly, a meta-analysis of data from an extensive literature survey indicates that a small proportion of the genetic variation in shoot Zn concentration can be attributed to evolutionary processes whose effects manifest above the family level. Remarkable insights into the evolutionary potential of plants to respond to elevated soil Zn have recently been made through detailed anatomical, physiological, chemical, genetic and molecular characterizations of the brassicaceous Zn hyperaccumulators Thlaspi caerulescens and Arabidopsis halleri. PMID- 17286819 TI - Plant resistance to parasitic plants: molecular approaches to an old foe. AB - Parasitic weeds pose severe constraint on major agricultural crops. Varying levels of resistance have been identified and exploited in the breeding programmes of several crops. However, the level of protection achieved to date is either incomplete or ephemeral. Resistance is mainly determined by the coexistence of several mechanisms controlled by multigenic and quantitative systems. Efficient control of the parasite requires a better understanding of the interaction and their associated resistance mechanisms at the histological, genetic and molecular levels. Application of postgenomic technologies and the use of model plants should improve the understanding of the plant-parasitic plant interaction and drive not only breeding programmes through either marker-assisted selection (MAS) or transgenesis but also the development of alternative methods to control the parasite. This review presents the current approaches targeting the characterization of resistance mechanisms and explores their potentiality to control parasitic plants. PMID- 17286820 TI - Guard cell-specific inhibition of Arabidopsis MPK3 expression causes abnormal stomatal responses to abscisic acid and hydrogen peroxide. AB - MAP kinases have been linked to guard cell signalling. Arabidopsis thaliana MAP Kinase 3 (MPK3) is known to be activated by abscisic acid (ABA) and hydrogen peroxide (H(2)O(2)), which also control stomatal movements. We therefore studied the possible role of MPK3 in guard cell signalling through guard cell-specific antisense inhibition of MPK3 expression. Such transgenic plants contained reduced levels of MPK3 mRNA in the guard cells and displayed partial insensitivity to ABA in inhibition of stomatal opening, but responded normally to this hormone in stomatal closure. However, ABA-induced stomatal closure was reduced compared with controls when cytoplasmic alkalinization was prevented with sodium butyrate. MPK3 antisense plants were less sensitive to exogenous H(2)O(2), both in inhibition of stomatal opening and in promotion of stomatal closure, thus MPK3 is required for the signalling of this compound. ABA-induced H(2)O(2) synthesis was normal in these plants, indicating that MPK3 probably acts in signalling downstream of H(2)O(2). These results provide clear evidence for the important role of MPK3 in the perception of ABA and H(2)O(2) in guard cells. PMID- 17286821 TI - Role of light and jasmonic acid signaling in regulating foliar phloem cell wall ingrowth development. AB - Phloem cells adjacent to sieve elements can possess wall invaginations. The role of light and jasmonic acid signaling in wall ingrowth development was examined in pea companion cells (CCs), Arabidopsis thaliana phloem parenchyma cells (PCs), and in Senecio vulgaris (with ingrowths in both cell types). Features characterized included wall ingrowths (from electron microscopic images), foliar vein density and photosynthetic capacity. In Arabidopsis, wall ingrowths were bulky compared with finger-like invaginations in pea and S. vulgaris. Relative to low light (LL), wall invagination in both CCs and PCs was greater in high light (HL). Treatment with methyl jasmonate in LL had no effect on CCs, but increased PC wall ingrowths. LL-to-HL transfer resulted in significantly less wall ingrowth in the fad7-1 fad8-1 (jasmonate-deficient) Arabidopsis mutant relative to the wild type. These results suggest that chloroplast oxidative status, via chloroplast-derived jasmonates, may modulate phloem structure and function. While CC wall ingrowths facilitate phloem loading by expanding the membrane area available for active uptake, one can speculate that phloem PC ingrowths may have two potential roles: to increase the efflux of sugars and/or protons into the apoplast to augment phloem loading; and/or to protect the phloem against pathogens and/or insects. PMID- 17286822 TI - Plant growth, biomass partitioning and soil carbon formation in response to altered lignin biosynthesis in Populus tremuloides. AB - We conducted a glasshouse mesocosm study that combined (13)C isotope techniques with wild-type and transgenic aspen (Populus tremuloides) in order to examine how altered lignin biosynthesis affects plant production and soil carbon formation. Our transgenic aspen lines expressed low stem lignin concentration but normal cellulose concentration, low lignin stem concentration with high cellulose concentration or an increased stem syringyl to guaiacyl lignin ratio. Large differences in stem lignin concentration observed across lines were not observed in leaves or fine roots. Nonetheless, low lignin lines accumulated 15-17% less root C and 33-43% less new soil C than the control line. Compared with the control line, transformed aspen expressing high syringyl lignin accumulated 30% less total plant C - a result of greatly reduced total leaf area - and 70% less new soil C. These findings suggest that altered stem lignin biosynthesis in Populus may have little effect on the chemistry of fine roots or leaves, but can still have large effects on plant growth, biomass partitioning and soil C formation. PMID- 17286823 TI - Calcium nutrition has a significant influence on wood formation in poplar. AB - To test the effects of calcium on wood formation, Populus tremula x Populus tremuloides clones were supplied with Hoagland solution modified in its calcium contents. Energy-dispersive X-ray analysis (EDXA) revealed an increase in calcium in the phloem, the cambium and the xylem elongation zone with increasing Ca(2+) supply in the nutrient solution. Using light and electron microscopy, a strong impact was shown on the cambial and the elongation zones under calcium starvation. Using Fourier transform infrared (FTIR) spectroscopy on wood and bark cells formed under calcium starvation, we detected a reduction of some absorptions, such as carbonyl and methoxy groups from S-lignin. Also, a significant reduction in fiber length was detected with decreasing calcium supply in the nutrient solution. High-performance liquid chromatography (HPLC) analysis revealed a large increase in sugar concentrations in the leaves, but reduced concentrations in the bark under Ca(2+) deficiency. In conclusion, our results show a significant influence of calcium on the structure, chemistry and physiology of wood formation. Thus, efficient Ca(2+) supply has to be considered a decisive factor in wood formation. PMID- 17286824 TI - Hydraulic redistribution of soil water in two old-growth coniferous forests: quantifying patterns and controls. AB - Although hydraulic redistribution of soil water (HR) by roots is a widespread phenomenon, the processes governing spatial and temporal patterns of HR are not well understood. We incorporated soil/plant biophysical properties into a simple model based on Darcy's law to predict seasonal trajectories of HR. We investigated the spatial and temporal variability of HR across multiple years in two old-growth coniferous forest ecosystems with contrasting species and moisture regimes by measurement of soil water content (theta) and water potential (Psi) throughout the upper soil profile, root distribution and conductivity, and relevant climate variables. Large HR variability within sites (0-0.5 mm d(-1)) was attributed to spatial patterns of roots, soil moisture and depletion. HR accounted for 3-9% of estimated total site water depletion seasonally, peaking at 0.16 mm d(-1) (ponderosa pine; Pinus ponderosa) or 0.30 mm d(-1) (Douglas-fir; Pseudotsuga menziesii), then declining as modeled pathway conductance dropped with increasing root cavitation. While HR can vary tremendously within a site, among years and among ecosystems, this variability can be explained by natural variability in Psi gradients and seasonal courses of root conductivity. PMID- 17286825 TI - The fate of photosynthetically-fixed carbon in Lolium perenne grassland as modified by elevated CO2 and sward management. AB - Prediction of the impact of climate change requires the response of carbon (C) flow in plant-soil systems to increased CO(2) to be understood. A mechanism by which grassland C sequestration might be altered was investigated by pulse labelling Lolium perenne swards, which had been subject to CO(2) enrichment and two levels of nitrogen (N) fertilization for 10 yr, with (14)CO(2). Over a 6-d period 40-80% of the (14)C pulse was exported from mature leaves, 1-2% remained in roots, 2-7% was lost as below-ground respiration, 0.1% was recovered in soil solution, and 0.2-1.5% in soil. Swards under elevated CO(2) with the lower N supply fixed more (14)C than swards grown in ambient CO(2), exported more fixed (14)C below ground and respired less than their high-N counterparts. Sward cutting reduced root (14)C, but plants in elevated CO(2) still retained 80% more (14)C below ground than those in ambient CO(2). The potential for below-ground C sequestration in grasslands is enhanced under elevated CO(2), but any increase is likely to be small and dependent upon grassland management. PMID- 17286826 TI - Elevated CO2 increases nitrogen rhizodeposition and microbial immobilization of root-derived nitrogen. AB - With this study, we aimed to determine how elevated CO(2) affects rhizodeposition and the cycling of rhizodeposited nitrogen (N) in the soil under C(3) and C(4) plants. In addition, we examined how cultivated genotypes of wheat (Triticum turgidum) and maize (Zea mays) responded to elevated CO(2) in comparison with their wild relatives. By constructing an N-transfer experiment we could directly assess cycling of the rhizodeposited N and trace the fate of rhizodeposited N in the soil and in receiver plants. Biomass production, rhizodeposition and cycling of root-borne N in maize genotypes were not affected by elevated CO(2). Elevated CO(2) stimulated above- and below-ground biomass production of the wheat genotypes on average by 38%, and increased rhizodeposition and immobilization of root-derived N on average by 30%. Concurrently, elevated CO(2) reduced mineral (15)N and re-uptake of the root-derived N by 50% in wheat. This study shows that elevated CO(2) may enhance N limitation by increasing N rhizodeposition and subsequent immobilization of the root-derived N. PMID- 17286827 TI - High nitrogen supply and carbohydrate content reduce fungal endophyte and alkaloid concentration in Lolium perenne. AB - The relationship between cool-season grasses and fungal endophytes is widely regarded as mutualistic, but there is growing uncertainty about whether changes in resource supply and environment benefit both organisms to a similar extent. Here, we infected two perennial ryegrass (Lolium perenne) cultivars (AberDove, Fennema) that differ in carbohydrate content with three strains of Neotyphodium lolii (AR1, AR37, common strain) that differ intrinsically in alkaloid profile. We grew endophyte-free and infected plants under high and low nitrogen (N) supply and used quantitative PCR (qPCR) to estimate endophyte concentrations in harvested leaf tissues. Endophyte concentration was reduced by 40% under high N supply, and by 50% in the higher sugar cultivar. These two effects were additive (together resulting in 75% reduction). Alkaloid production was also reduced under both increased N supply and high sugar cultivar, and for three of the four alkaloids quantified, concentrations were linearly related to endophyte concentration. The results stress the need for wider quantification of fungal endophytes in the grassland-foliar endophyte context, and have implications for how introducing new cultivars, novel endophytes or increasing N inputs affect the role of endophytes in grassland ecosystems. PMID- 17286828 TI - Interactions between extraradical ectomycorrhizal mycelia, microbes associated with the mycelia and growth rate of Norway spruce (Picea abies) clones. AB - Despite their ecological relevance, field studies of the extraradical mycelia of ectomycorrhizal (ECM) fungi are rare. Here we examined in situ interactions between ECM mycelia and host vigour. Ectomycorrhizal mycelia were harvested with in-growth mesh bags buried under Norway spruce (Picea abies) clones planted in 1994 in a randomized block design. Mycelial biomass was determined and fungal species were identified by denaturing gradient gel electrophoresis (DGGE) and sequencing of the internal transcribed spacer 1 (ITS1) region. Microbial community structure in the mycelium was investigated by phospholipid fatty acid (PLFA) profiling. Compared to slow-growing spruce clones, fast-growing clones tended to support denser mycelia where the relative proportions of Atheliaceae fungi and PLFAs indicative of Gram-positive bacteria were higher. Ascomycetes and PLFAs representative of Gram-negative bacteria were more common with slow-growing clones. In general, the ECM mycelial community was similar to the ECM root-tip community. Growth rate of the hosts, the ECM mycelial community and the microbes associated with the mycelium were related, suggesting multitrophic interactions between trees, fungi and bacteria. PMID- 17286829 TI - How does arbuscular mycorrhizal symbiosis regulate root hydraulic properties and plasma membrane aquaporins in Phaseolus vulgaris under drought, cold or salinity stresses? AB - Here, we evaluated how the arbuscular mycorrhizal (AM) symbiosis regulates root hydraulic properties and root plasma membrane aquaporins (PIP) under different stresses sharing a common osmotic component. Phaseolus vulgaris plants were inoculated or not with the AM fungus Glomus intraradices, and subjected to drought, cold or salinity. Stress effects on root hydraulic conductance (L), PIP gene expression and protein abundance were evaluated. Under control conditions, L in AM plants was about half that in nonAM plants. However, L was decreased as a result of the three stresses in nonAM plants, while it was almost unchanged in AM plants. At the same time, PIP2 protein abundance and phosphorylation state presented the same trend as L. Finally, the expression of each PIP gene responded differently to each stress and was dependent on the AM fungal presence. Differential expression of the PIP genes studied under each stress depending on the AM fungal presence may indicate a specific function and regulation by the AM symbiosis of each gene under the specific conditions of each stress tested. PMID- 17286830 TI - Conservation and divergence of both phosphate- and mycorrhiza-regulated physiological responses and expression patterns of phosphate transporters in solanaceous species. AB - Here, orthologous genes of six phosphate transporter (PiT) genes, which are members of the Pht1 and Pht2 families in tomato and potato, have been cloned from the solanaceous species pepper, eggplant and tobacco. Overall, expressions of these genes in pepper, eggplant and tobacco showed similar patterns to those in tomato and potato: P-starvation enhancement in both leaves and roots for Pht1;1, P-depletion induction exclusively in roots for Pht1;2, mycorrhizal enhancement for Pht1;3, and mycorrhizal induction for both Pht1;4 and Pht1;5. In the roots of nonmycorrhizal eggplant, SmPht1;3, SmPht1;4 and SmPht1;5 were also expressed under extreme P starvation. Mycorrhizal symbiosis under high-P supply conditions reduced plant growth, with concurrent enhancement of Pht1;2 expression in the roots of pepper as well as eggplant. In addition, the mycorrhizal symbiosis down regulated the expression of Pht2;1 genes greatly in the leaves of pepper and tobacco. The discrepancies between the evolutionary distances of the PiT genes and their expression patterns among the five species suggest greater complexity in function of PiT in plants than previously expected. PMID- 17286831 TI - Stomatal deregulation in Plasmopara viticola-infected grapevine leaves. AB - In grapevine, the penetration and sporulation of Plasmopara viticola occur via stomata, suggesting functional relationships between guard cells and the pathogen. This assumption was supported by our first observation that grapevine (Vitis vinifera cv. Marselan) cuttings infected by P. viticola wilted more rapidly than healthy ones when submitted to water starvation. Here, complementary approaches measuring stomatal conductance and infrared thermographic and microscopic observations were used to investigate stomatal opening/closure in response to infection. In infected leaves, stomata remained open in darkness and during water stress, leading to increased transpiration. This deregulation was restricted to the colonized area, was not systemic and occurred before the appearance of symptoms. Cytological observations indicated that stomatal lock open was not related to mechanical forces resulting from the presence of the pathogen in the substomatal cavity. In contrast to healthy leaves, stomatal closure in excised infected leaves could not be induced by a water deficit or abscisic acid (ABA) treatment. However, ABA induced stomatal closure in epidermal peels from infected leaves, indicating that guard cells remained functional. These data indicate that the oomycete deregulates guard cell functioning, causing significant water losses. This effect could be attributed to a nonsystemic compound, produced by the oomycete or by the infected plant, which inhibits stomatal closure or induces stomatal opening; or a reduction of the back-pressure exerted by surrounding epidermal cells. Both hypotheses are under investigation. PMID- 17286832 TI - A multicomponent, elicitor-inducible cystatin complex in tomato, Solanum lycopersicum. AB - We assessed the ability of the fungal elicitor arachidonic acid to induce cystatin genes in tomato (Solanum lycopersicum), using a cDNA expression library from arachidonate-treated leaves. The cDNAs of two novel cystatins were isolated, coding for an approx. 11-kDa protein, SlCYS10; and for a 23.6-kDa protein, SlCYS9, bearing an N-terminal signal peptide and a long, 11.5-kDa extension at the C terminus. Both genes were induced by arachidonate but not by methyl jasmonate, an inducer of the 88-kDa eight-unit cystatin, multicystatin, accumulated in the cytosol of leaf cells upon herbivory. A truncated form of SlCYS9, tSlCYS9, was produced by deletion of the C-terminal extension to assess the influence of this structural element on the cystatin moiety. As shown by kinetic and stability assays with recombinant variants expressed in Escherichia coli, deleting the extension influenced both the overall stability and inhibitory potency of SlCYS9 against cysteine proteases of herbivorous organisms. These findings provide evidence for a multicomponent elicitor-inducible cystatin complex in tomato, including at least 10 cystatin units produced via two metabolic routes. PMID- 17286833 TI - Chemical facilitation and induced pathogen resistance mediated by a root-secreted phytotoxin. AB - The flavonol (+/-)-catechin is an allelochemical produced by the invasive weed Centaurea maculosa (spotted knapweed). The full effects of (+/-)-catechin on plant communities in both the native and the introduced ranges of C. maculosa remain uncertain. Here, by supplementing plant growth media with (+/-)-catechin, we showed that low (+/-)-catechin concentrations may induce growth and defense responses in neighboring plants. Doses of the allelochemical lower than the minimum inhibitory concentration (MIC) induced growth in Arabidopsis thaliana; plants treated with 25 microg ml(-1) (+/-)-catechin accumulated more than twice the biomass of untreated control plants. Further, pretreatment of A. thaliana roots with low concentrations of (+/-)-catechin induced resistance to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 in A. thaliana leaves. Low doses of (+/-)-catechin resulted in moderate increases in reactive oxygen species (ROS) in the meristems of treated plants, which may have loosened the cell walls and thus increased growth. Experiments with A. thaliana mutants indicated that (+/-)-catechin induces pathogen resistance by up-regulating defense genes via the salicylic acid (SA)/nonexpressor of pathogenesis related protein 1 (NPR1)-dependent pathway. Our results suggest that the growth and defense-inducing effects of (+/-)-catechin are concentration dependent, as (+/-) catechin at higher concentrations is phytotoxic, thus suggesting the potential for hormesis to occur in nature. PMID- 17286834 TI - Is the ability of biocontrol fluorescent pseudomonads to produce the antifungal metabolite 2,4-diacetylphloroglucinol really synonymous with higher plant protection? AB - The antifungal compound 2,4-diacetylphloroglucinol (Phl) contributes to biocontrol in pseudomonads, but whether or not Phl(+) biocontrol pseudomonads display higher plant-protecting activity than Phl(-) biocontrol pseudomonads remains to be demonstrated. This issue was addressed by assessing 230 biocontrol fluorescent pseudomonads selected from a collection of 3132 bacterial isolates obtained from 63 soils worldwide. One-third of the biocontrol pseudomonads were Phl(+) and almost all Phl(+) isolates also produced hydrogen cyanide (HCN). The only Phl(+) HCN(-) strain did harbor hcn genes, but with the deletion of a 134 bp hcnC fragment corresponding to an ADP-binding motif. Statistical analysis of biocontrol isolate distributions indicated that Phl production ability was associated with superior disease suppression activity in the Pythium-cucumber and Fusarium-tomato pathosystems, but this was also the case with HCN production ability. However, HCN significance was not as strong, as indicated both by the comparison of Phl(-) HCN(+) and Phl(-) HCN(-) strains and by correlation analyses. This is the first population-level demonstration of the higher plant protecting activity of Phl(+) biocontrol pseudomonads in comparison with Phl(-) biocontrol pseudomonads. PMID- 17286835 TI - Mycothiol-dependent proteins in actinomycetes. AB - The pseudodisaccharide mycothiol is present in millimolar levels as the dominant thiol in most species of Actinomycetales. The primary role of mycothiol is to maintain the intracellular redox homeostasis. As such, it acts as an electron acceptor/donor and serves as a cofactor in detoxification reactions for alkylating agents, free radicals and xenobiotics. In addition, like glutathione, mycothiol may be involved in catabolic processes with an essential role for growth on recalcitrant chemicals such as aromatic compounds. Following a little over a decade of research since the discovery of mycothiol in 1994, we summarize the current knowledge about the role of mycothiol as an enzyme cofactor and consider possible mycothiol-dependent enzymes. PMID- 17286836 TI - Pointing out new news, old news, and absent referents at 12 months of age. AB - There is currently controversy over the nature of 1-year-olds' social-cognitive understanding and motives. In this study we investigated whether 12-month-old infants point for others with an understanding of their knowledge states and with a prosocial motive for sharing experiences with them. Declarative pointing was elicited in four conditions created by crossing two factors: an adult partner (1) was already attending to the target event or not, and (2) emoted positively or neutrally. Pointing was also coded after the event had ceased. The findings suggest that 12-month-olds point to inform others of events they do not know about, that they point to share an attitude about mutually attended events others already know about, and that they can point (already prelinguistically) to absent referents. These findings provide strong support for a mentalistic and prosocial interpretation of infants' prelinguistic communication. PMID- 17286837 TI - Risk-taking and the adolescent brain: who is at risk? AB - Relative to other ages, adolescence is described as a period of increased impulsive and risk-taking behavior that can lead to fatal outcomes (suicide, substance abuse, HIV, accidents, etc.). This study was designed to examine neural correlates of risk-taking behavior in adolescents, relative to children and adults, in order to predict who may be at greatest risk. Activity in reward related neural circuitry in anticipation of a large monetary reward was measured with functional magnetic resonance imaging, and anonymous self-report ratings of risky behavior, anticipation of risk and impulsivity were acquired in individuals between the ages of 7 and 29 years. There was a positive association between accumbens activity and the likelihood of engaging in risky behavior across development. This activity also varied as a function of individuals' ratings of anticipated positive or negative consequences of such behavior. Impulsivity ratings were not associated with accumbens activity, but rather with age. These findings suggest that during adolescence, some individuals may be especially prone to engage in risky behaviors due to developmental changes in concert with variability in a given individual's predisposition to engage in risky behavior, rather than to simple changes in impulsivity. PMID- 17286838 TI - Listening to language at birth: evidence for a bias for speech in neonates. AB - The nature and origin of the human capacity for acquiring language is not yet fully understood. Here we uncover early roots of this capacity by demonstrating that humans are born with a preference for listening to speech. Human neonates adjusted their high amplitude sucking to preferentially listen to speech, compared with complex non-speech analogues that controlled for critical spectral and temporal parameters of speech. These results support the hypothesis that human infants begin language acquisition with a bias for listening to speech. The implications of these results for language and communication development are discussed. For a commentary on this article see Rosen and Iverson (2007). PMID- 17286839 TI - Constructing adequate non-speech analogues: what is special about speech anyway? AB - Vouloumanos and Werker (2007) claim that human neonates have a (possibly innate) bias to listen to speech based on a preference for natural speech utterances over sine-wave analogues. We argue that this bias more likely arises from the strikingly different saliency of voice melody in the two kinds of sounds, a bias that has already been shown to be learned pre-natally. Possible avenues of research to address this crucial issue are proposed, based on a consideration of the distinctive acoustic properties of speech. This is a commentary on Vouloumanos and Werker (2007). PMID- 17286841 TI - Looking compensates for the distance between mother and infant chimpanzee. AB - The development of visual interaction between mother and infant has received much attention in developmental psychology, not only in humans, but also in non-human primates. Recently, comparative developmental approaches have investigated whether the mechanisms that underlie these behaviors are common in primates. In the present study, we focused on the question of whether chimpanzee mother and infant replace physical contact with visual contact. To test this hypothesis, we measured non-synchronous looking ('looking') between mother and infant. A unique setting, in which the mother chimpanzee stayed in one location and the infant chimpanzee moved freely, allowed us to analyze the relation between the visual interaction and the distance of a mother-infant pair during the first year of life. Our results showed that 'looking' increased when body contact decreased or when the distance between mother and infant increased. We also show a behavioral sequence of typical 'secure base' behavior, a behavior characterized by the infant regularly returning to its mother when exploring the environment. These findings imply that attachment between mother and infant chimpanzee appears to develop in a similar fashion as in humans. PMID- 17286842 TI - Crawling is associated with more flexible memory retrieval by 9-month-old infants. AB - In the present experiment, we used a deferred imitation paradigm to explore the effect of crawling on memory retrieval by 9-month-old human infants. Infants observed an experimenter demonstrate a single target action with a novel object and their ability to reproduce that action was assessed after a 24-hr delay. Some infants were tested with the demonstration stimulus in the demonstration context and some infants were tested with a different stimulus in a different context. Half of the infants in each test condition were crawling at the time of participation and half were not. Both crawling and non-crawling infants exhibited retention when tested with the demonstration stimulus in the demonstration context, but only infants who were crawling by 9 months of age exhibited retention when tested with a different stimulus in a different context. These findings demonstrate that the onset of independent locomotion is associated with more flexible memory retrieval during the first year of life. PMID- 17286843 TI - Acquisition of early words from single-word and sentential contexts. AB - Toddlers 15 and 18 months of age were exposed to audiovisual recordings of two novel words paired with novel toys. The words were presented in familiar sentence frames or in isolation. Linguistic context had a greater effect on younger than on older infants. Specifically, 15-month-old boys exhibited successful learning only in the context of single words, and 15-month-old girls did so only for words presented in sentences. Older infants acquired the new words from both contexts, and they learned more rapidly than younger infants. Receptive and expressive vocabulary made no independent contribution to performance. PMID- 17286844 TI - Now I see it but you don't: 14-month-olds can represent another person's visual perspective. AB - Twelve- and 14-month-old infants' ability to represent another person's visual perspective (Level-1 visual perspective taking) was studied in a looking-time paradigm. Fourteen-month-olds looked longer at a person reaching for and grasping a new object when the old goal-object was visible than when it was invisible to the person (but visible to the infant). These findings are consistent with the interpretation that infants 'rationalized' the person's reach for a new object when the old goal-object was out of sight. Twelve-month-olds did not distinguish between test conditions. The present findings are consistent with recent research on infants' developing understanding of seeing. PMID- 17286845 TI - The informative value of emotional expressions: 'social referencing' in mother child pretense. AB - Mothers begin to pretend with their children during the second year, when children still have much to learn about the real world. Although it would be easy to confuse what is pretend with what is real, children at this young age often demonstrate comprehension during pretense situations. It is plausible that social referencing, in which the child uses the mother's emotional expression as a guide to behavior, might facilitate this emerging knowledge by signaling to the child not to take the pretend situation seriously. Data from 32 pairs of mothers and their 18-month-olds who had engaged in pretend and real snack behaviors were subjected to a sequential analysis to investigate a social referencing interpretation. Consistent with our hypothesis, behaviors suggestive of a baby's understanding pretense were more likely to follow a specific combination of behaviors consistent with social referencing than other combinations of behaviors. These results provide support for the possibility that children use information obtained through social referencing to assist understanding during pretense interactions. PMID- 17286847 TI - The role of type and token frequency in using past tense morphemes correctly. AB - Type and token frequency have been thought to be important in the acquisition of past tense morphology, particularly in differentiating regular and irregular forms. In this study we tested the role of frequency in two ways: (1) in bilingual children, who typically use and hear either language less often than monolingual children and (2) cross-linguistically: French and English have different patterns of frequency of regular/irregular verbs. Ten French-English bilingual children, 10 French monolingual and 10 English monolingual children between 4 and 6 years watched a cartoon and re-told the story. The results demonstrated that the bilingual children were less accurate than the monolingual children. Their accuracy in both French and English regular and irregular verbs corresponded to frequency in the input language. These results are consistent with the hypothesis that children learn past tense morphemes by analogy with other words in their vocabularies. We propose a developmental sequence based on conservative generalization across a growing set of verbs. PMID- 17286848 TI - Social grooming in the kindergarten: the emergence of flattery behavior. AB - The present study examined the emergence of flattery behavior in young children and factors that might affect whether and how it is displayed. Preschool children between the ages of 3 and 6 years were asked to rate drawings produced by either a present or absent adult stranger (Experiments 1 and 2), child stranger (Experiments 2 and 3), classmate, or the children's own teacher (Experiment 3). Young preschoolers gave consistent ratings to the same drawing by the person regardless of whether the person was absent or present. In contrast, many older preschoolers gave more flattering ratings to the drawing when the person was present than in the person's absence. Also, older preschoolers displayed flattery regardless of whether the recipient was an adult or a child. However, they displayed flattery to a greater extent towards familiar individuals than unfamiliar ones, demonstrating an emerging sensitivity to social contexts in which flattery is used. These findings suggest that preschoolers have already learned not to articulate bluntly their true feelings and thoughts about others. Rather, they are able to manipulate their communications according to social context. PMID- 17286849 TI - Impairments in monkey and human face recognition in 2-year-old toddlers with Autism Spectrum Disorder and Developmental Delay. AB - Face recognition impairments are well documented in older children with Autism Spectrum Disorders (ASD); however, the developmental course of the deficit is not clear. This study investigates the progressive specialization of face recognition skills in children with and without ASD. Experiment 1 examines human and monkey face recognition in 2-year-old children with ASD, matched for nonverbal mental age (NVMA) with developmentally delayed (DD) children, and typically developing children (TD), using the Visual Paired Comparison (VPC) paradigm. Results indicate that, consistent with the other-species effect, TD controls show enhanced recognition of human but not monkey faces; however, neither the ASD nor the DD group show evidence of face recognition regardless of the species. Experiment 2 examines the same question in a group of older 3- to 4-year-old developmentally disabled (ASD and DD) children as well as in typical controls. In this experiment, both human and monkey faces are recognized by all three groups. The results of Experiments 1 and 2 suggest that difficulties in face processing, as measured by the VPC paradigm, are common in toddlers with ASD as well as DD, but that these deficits tend to disappear by early preschool age. In addition, the experiments show that higher efficacy of incidental encoding and recognition of facial identity in a context of passive exposure is positively related to nonverbal cognitive skills and age, but not to overall social interaction skills or greater attention to faces exhibited in naturalistic contexts. PMID- 17286846 TI - Infant information processing and family history of specific language impairment: converging evidence for RAP deficits from two paradigms. AB - An infant's ability to process auditory signals presented in rapid succession (i.e. rapid auditory processing abilities [RAP]) has been shown to predict differences in language outcomes in toddlers and preschool children. Early deficits in RAP abilities may serve as a behavioral marker for language-based learning disabilities. The purpose of this study is to determine if performance on infant information processing measures designed to tap RAP and global processing skills differ as a function of family history of specific language impairment (SLI) and/or the particular demand characteristics of the paradigm used. Seventeen 6- to 9-month-old infants from families with a history of specific language impairment (FH+) and 29 control infants (FH-) participated in this study. Infants' performance on two different RAP paradigms (head-turn procedure [HT] and auditory-visual habituation/recognition memory [AVH/RM]) and on a global processing task (visual habituation/recognition memory [VH/RM]) was assessed at 6 and 9 months. Toddler language and cognitive skills were evaluated at 12 and 16 months. A number of significant group differences were seen: FH+ infants showed significantly poorer discrimination of fast rate stimuli on both RAP tasks, took longer to habituate on both habituation/recognition memory measures, and had lower novelty preference scores on the visual habituation/recognition memory task. Infants' performance on the two RAP measures provided independent but converging contributions to outcome. Thus, different mechanisms appear to underlie performance on operantly conditioned tasks as compared to habituation/recognition memory paradigms. Further, infant RAP processing abilities predicted to 12- and 16-month language scores above and beyond family history of SLI. The results of this study provide additional support for the validity of infant RAP abilities as a behavioral marker for later language outcome. Finally, this is the first study to use a battery of infant tasks to demonstrate multi-modal processing deficits in infants at risk for SLI. PMID- 17286850 TI - Two-dimensional tracking and TDI are consistent methods for evaluating myocardial longitudinal peak strain in left and right ventricle basal segments in athletes. AB - BACKGROUND: Myocardial contractility can be investigated using longitudinal peak strain. It can be calculated using the Doppler-derived TDI method and the non Doppler method based on tissue tracking on B-mode images. Both are validated and show good reproducibility, but no comparative analysis of their results has yet been conducted. This study analyzes the results obtained from the basal segments of the ventricular chambers in a group of athletes. METHODS: 30 regularly-trained athletes were submitted to an echocardiography at rest and after handgrip. Starting from the four-chamber view, overall myocardial function and regional velocities were evaluated. The images obtained were processed to determine strain in left and right ventricle basal segments. Strain was calculated using the TDI method and a validated "speckle tracking" or, more correctly, "feature tracking" algorithm. The statistical analysis included a Student's t-test (p < 0.05). RESULTS: The range of strain values obtained is in agreement with the data reported in the literature. In the left ventricle (LV) the average strain values of the basal segments calculated with TDI on IVS and LW at rest and after stress were: -21.05 +/- 3.31; -20.41 +/- 2.99 and -20.05 +/- 2.61; -21.20 +/- 2.37, respectively. In the right ventricle (RV) the same method gave IVS and LW strain values at rest of -22.22 +/- 2.58 ; -24.42 +/- 5.84, and after HG of -22.02 +/- 5.20 ;-23.93 +/- 6.34. The values obtained using feature tracking were: LV at rest -20.48 +/- 2.65 for IVS, and -21.25 +/- 2.85 for LW; LV after HG: -19.48 +/- 3 for IVS and -21.69 +/- 3.85 for LW. In RV at rest: -21.46 +/- 3.25 for IVS and 24.13 +/- 5.86 for LW; RV after HG: -24.79 +/- 7.9 for IVS and -24.13 +/- 7.0 for LW. Tissue Doppler and "feature tracking" methods showed the respective consistency of the results in the basal segments of myocardial ventricle walls. CONCLUSION: Provided that echographic imaging is good, strain can be computed in athletes by both Doppler-derived and tracking methods. It is technically feasible to use both -interchangeably, at least in basal segments. PMID- 17286853 TI - Error-threshold exists in fitness landscapes with lethal mutants. AB - BACKGROUND: One of the important insights of quasi-species theory is an error threshold. The error-threshold is the error rate of replication above which the sudden onset of the population delocalization from the fittest genotype occurs despite Darwinian selection; i.e., the break down of evolutionary optimization. However, a recent article by Wilke in this journal, after reviewing the previous studies on the error-threshold, concluded that the error-threshold does not exist if lethal mutants are taken into account in a fitness landscape. Since lethal mutants obviously exist in reality, this has a significant implication about biological evolution. However, the study of Wagner and Krall on which Wilke's conclusion was based considered mutation-selection dynamics in one-dimensional genotype space with the assumption that a genotype can mutate only to an adjoining genotype in the genotype space. In this article, we study whether the above conclusion holds in high-dimensional genotype space without the assumption of the adjacency of mutations, where the consequences of mutation-selection dynamics can be qualitatively different. RESULTS: To examine the effect of mutant lethality on the existence of the error-threshold, we extend the quasi-species equation by taking the lethality of mutants into account, assuming that lethal genotypes are uniformly distributed in the genotype space. First, with the simplification of neglecting back mutations, we calculate the error-threshold as the maximum allowable mutation rate for which the fittest genotype can survive. Second, with the full consideration of back mutations, we study the equilibrium population distribution and the ancestor distribution in the genotype space as a function of error rate with and without lethality in a multiplicative fitness landscape. The results show that a high lethality of mutants actually introduces an error-threshold in a multiplicative fitness landscape in sharp contrast to the conclusion of Wilke. Furthermore, irrespective of the lethality of mutants, the delocalization of the population from the fittest genotype occurs for an error rate much smaller than random replication. Finally, the results are shown to extend to a system of finite populations. CONCLUSION: High lethality of mutants introduces an error-threshold in a multiplicative fitness landscape. Furthermore, irrespective of the lethality of mutants, the break down of evolutionary optimization happens for an error rate much smaller than random replication. PMID- 17286852 TI - Loss of Parp-1 affects gene expression profile in a genome-wide manner in ES cells and liver cells. AB - BACKGROUND: Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation of various genes as a coactivator or a corepressor by modulating chromatin structure. However, the impact of Parp-1-deficiency on the regulation of genome-wide gene expression has not been fully studied yet. RESULTS: We employed a microarray analysis covering 12,488 genes and ESTs using mouse Parp-1-deficient (Parp-1-/-) embryonic stem (ES) cell lines and the livers of Parp-1-/- mice and their wild-type (Parp-1+/+) counterparts. Here, we demonstrate that of the 9,907 genes analyzed, in Parp-1-/- ES cells, 9.6% showed altered gene expression. Of these, 6.3% and 3.3% of the genes were down- or up-regulated by 2-fold or greater, respectively, compared with Parp-1+/+ ES cells (p < 0.05). In the livers of Parp-1-/- mice, of the 12,353 genes that were analyzed, 2.0% or 1.3% were down- and up-regulated, respectively (p < 0.05). Notably, the number of down-regulated genes was higher in both ES cells and livers, than that of the up-regulated genes. The genes that showed altered expression in ES cells or in the livers are ascribed to various cellular processes, including metabolism, signal transduction, cell cycle control and transcription. We also observed expression of the genes involved in the pathway of extraembryonic tissue development is augmented in Parp-1-/- ES cells, including H19. After withdrawal of leukemia inhibitory factor, expression of H19 as well as other trophoblast marker genes were further up-regulated in Parp-1-/- ES cells compared to Parp-1+/+ ES cells. CONCLUSION: These results suggest that Parp-1 is required to maintain transcriptional regulation of a wide variety of genes on a genome-wide scale. The gene expression profiles in Parp-1-deficient cells may be useful to delineate the functional role of Parp-1 in epigenetic regulation of the genomes involved in various biological phenomena. PMID- 17286851 TI - Fluxome analysis using GC-MS. AB - Fluxome analysis aims at the quantitative analysis of in vivo carbon fluxes in metabolic networks, i. e. intracellular activities of enzymes and pathways. It allows investigating the effects of genetic or environmental modifications and thus precisely provides a global perspective on the integrated genetic and metabolic regulation within the intact metabolic network. The experimental and computational approaches developed in this area have revealed fascinating insights into metabolic properties of various biological systems. Most of the comprehensive approaches for metabolic flux studies today involve isotopic tracer studies and GC-MS for measurement of the labeling pattern of metabolites. Initially developed and applied mainly in the field of biomedicine these GC-MS based metabolic flux approaches have been substantially extended and optimized during recent years and today display a key technology in metabolic physiology and biotechnology. PMID- 17286854 TI - Reliable allele detection using SNP-based PCR primers containing Locked Nucleic Acid: application in genetic mapping. AB - BACKGROUND: The diploid, Solanum caripense, a wild relative of potato and tomato, possesses valuable resistance to potato late blight and we are interested in the genetic base of this resistance. Due to extremely low levels of genetic variation within the S. caripense genome it proved impossible to generate a dense genetic map and to assign individual Solanum chromosomes through the use of conventional chromosome-specific SSR, RFLP, AFLP, as well as gene- or locus-specific markers. The ease of detection of DNA polymorphisms depends on both frequency and form of sequence variation. The narrow genetic background of close relatives and inbreds complicates the detection of persisting, reduced polymorphism and is a challenge to the development of reliable molecular markers. Nonetheless, monomorphic DNA fragments representing not directly usable conventional markers can contain considerable variation at the level of single nucleotide polymorphisms (SNPs). This can be used for the design of allele-specific molecular markers. The reproducible detection of allele-specific markers based on SNPs has been a technical challenge. RESULTS: We present a fast and cost-effective protocol for the detection of allele-specific SNPs by applying Sequence Polymorphism-Derived (SPD) markers. These markers proved highly efficient for fingerprinting of individuals possessing a homogeneous genetic background. SPD markers are obtained from within non-informative, conventional molecular marker fragments that are screened for SNPs to design allele-specific PCR primers. The method makes use of primers containing a single, 3'-terminal Locked Nucleic Acid (LNA) base. We demonstrate the applicability of the technique by successful genetic mapping of allele-specific SNP markers derived from monomorphic Conserved Ortholog Set II (COSII) markers mapped to Solanum chromosomes, in S. caripense. By using SPD markers it was possible for the first time to map the S. caripense alleles of 16 chromosome-specific COSII markers and to assign eight of the twelve linkage groups to consensus Solanum chromosomes. CONCLUSION: The method based on individual allelic variants allows for a level-of-magnitude higher resolution of genetic variation than conventional marker techniques. We show that the majority of monomorphic molecular marker fragments from organisms with reduced heterozygosity levels still contain SNPs that are sufficient to trace individual alleles. PMID- 17286855 TI - Mapping of transcription start sites of human retina expressed genes. AB - BACKGROUND: The proper assembly of the transcriptional initiation machinery is a key regulatory step in the execution of the correct program of mRNA synthesis. The use of alternative transcription start sites (TSSs) provides a mechanism for cell and tissue specific gene regulation. Our knowledge of transcriptional initiation sequences in the human genome is limited despite the availability of the complete genome sequence. While genome wide experimental and bioinformatic approaches are improving our knowledge of TSSs, they lack information concerning genes expressed in a restricted manner or at very low levels, such as tissue specific genes. RESULTS: In this study we describe the mapping of TSSs of genes expressed in human retina. Genes have been selected on the basis of their physiological or developmental role in this tissue. Our work combines in silico analysis of ESTs and known algorithm predictions together with their experimental validation via Cap-finder RACE. We report here the TSSs mapping of 54 retina expressed genes: we retrieved new sequences for 41 genes, some of which contain un-annotated exons. Results can be grouped into five categories, compared to the RefSeq; (i) TSS located in new first exons, (ii) splicing variation of the second exon, (iii) extension of the annotated first exon, (iv) shortening of the annotated first exon, (v) confirmation of previously annotated TSS. CONCLUSION: In silico and experimental analysis of the transcripts proved to be essential for the ultimate mapping of TSSs. Our results highlight the necessity of a tissue specific approach to complete the existing gene annotation. The new TSSs and transcribed sequences are essential for further exploration of the promoter and other cis-regulatory sequences at the 5'end of genes. PMID- 17286856 TI - PlnTFDB: an integrative plant transcription factor database. AB - BACKGROUND: Transcription factors (TFs) are key regulatory proteins that enhance or repress the transcriptional rate of their target genes by binding to specific promoter regions (i.e. cis-acting elements) upon activation or de-activation of upstream signaling cascades. TFs thus constitute master control elements of dynamic transcriptional networks. TFs have fundamental roles in almost all biological processes (development, growth and response to environmental factors) and it is assumed that they play immensely important functions in the evolution of species. In plants, TFs have been employed to manipulate various types of metabolic, developmental and stress response pathways. Cross-species comparison and identification of regulatory modules and hence TFs is thought to become increasingly important for the rational design of new plant biomass. Up to now, however, no computational repository is available that provides access to the largely complete sets of transcription factors of sequenced plant genomes. DESCRIPTION: PlnTFDB is an integrative plant transcription factor database that provides a web interface to access large (close to complete) sets of transcription factors of several plant species, currently encompassing Arabidopsis thaliana (thale cress), Populus trichocarpa (poplar), Oryza sativa (rice), Chlamydomonas reinhardtii and Ostreococcus tauri. It also provides an access point to its daughter databases of a species-centered representation of transcription factors (OstreoTFDB, ChlamyTFDB, ArabTFDB, PoplarTFDB and RiceTFDB). Information including protein sequences, coding regions, genomic sequences, expressed sequence tags (ESTs), domain architecture and scientific literature is provided for each family. CONCLUSION: We have created lists of putatively complete sets of transcription factors and other transcriptional regulators for five plant genomes. They are publicly available through http://plntfdb.bio.uni-potsdam.de. Further data will be included in the future when the sequences of other plant genomes become available. PMID- 17286857 TI - Predictive modeling of plant messenger RNA polyadenylation sites. AB - BACKGROUND: One of the essential processing events during pre-mRNA maturation is the post-transcriptional addition of a polyadenine [poly(A)] tail. The 3'-end poly(A) track protects mRNA from unregulated degradation, and indicates the integrity of mRNA through recognition by mRNA export and translation machinery. The position of a poly(A) site is predetermined by signals in the pre-mRNA sequence that are recognized by a complex of polyadenylation factors. These signals are generally tri-part sequence patterns around the cleavage site that serves as the future poly(A) site. In plants, there is little sequence conservation among these signal elements, which makes it difficult to develop an accurate algorithm to predict the poly(A) site of a given gene. We attempted to solve this problem. RESULTS: Based on our current working model and the profile of nucleotide sequence distribution of the poly(A) signals and around poly(A) sites in Arabidopsis, we have devised a Generalized Hidden Markov Model based algorithm to predict potential poly(A) sites. The high specificity and sensitivity of the algorithm were demonstrated by testing several datasets, and at the best combinations, both reach 97%. The accuracy of the program, called poly(A) site sleuth or PASS, has been demonstrated by the prediction of many validated poly(A) sites. PASS also predicted the changes of poly(A) site efficiency in poly(A) signal mutants that were constructed and characterized by traditional genetic experiments. The efficacy of PASS was demonstrated by predicting poly(A) sites within long genomic sequences. CONCLUSION: Based on the features of plant poly(A) signals, a computational model was built to effectively predict the poly(A) sites in Arabidopsis genes. The algorithm will be useful in gene annotation because a poly(A) site signifies the end of the transcript. This algorithm can also be used to predict alternative poly(A) sites in known genes, and will be useful in the design of transgenes for crop genetic engineering by predicting and eliminating undesirable poly(A) sites. PMID- 17286858 TI - Perceived efficacy of herbal remedies by users accessing primary healthcare in Trinidad. AB - BACKGROUND: The increasing global popularity of herbal remedies requires further investigation to determine the probable factors driving this burgeoning phenomenon. We propose that the users' perception of efficacy is an important factor and assessed the perceived efficacy of herbal remedies by users accessing primary health facilities throughout Trinidad. Additionally, we determined how these users rated herbal remedies compared to conventional allopathic medicines as being less, equally or more efficacious. METHODS: A descriptive cross sectional study was undertaken at 16 randomly selected primary healthcare facilities throughout Trinidad during June-August 2005. A de novo, pilot-tested questionnaire was interviewer-administered to confirmed herbal users (previous or current). Stepwise multiple regression analysis was done to determine the influence of predictor variables on perceived efficacy and comparative efficacy with conventional medicines. RESULTS: 265 herbal users entered the study and cited over 100 herbs for the promotion of health/wellness and the management of specific health concerns. Garlic was the most popular herb (in 48.3% of the sample) and was used for the common cold, cough, fever, as 'blood cleansers' and carminatives. It was also used in 20% of hypertension patients. 230 users (86.8%) indicated that herbs were efficacious and perceived that they had equal or greater efficacy than conventional allopathic medicines. Gender, ethnicity, income and years of formal education did not influence patients' perception of herb efficacy; however, age did (p = 0.036). Concomitant use of herbs and allopathic medicines was relatively high at 30%; and most users did not inform their attending physician. CONCLUSION: Most users perceived that herbs were efficacious, and in some instances, more efficacious than conventional medicines. We suggest that this perception may be a major contributing factor influencing the sustained and increasing popularity of herbs. Evidence-based research in the form of randomized controlled clinical trials should direct the proper use of herbs to validate (or otherwise) efficacy and determine safety. In the Caribbean, most indigenous herbs are not well investigated and this points to the urgent need for biomedical investigations to assess the safety profile and efficacy of our popular medicinal herbs. PMID- 17286860 TI - Single nucleotide polymorphisms (SNPs) distinguish Indian-origin and Chinese origin rhesus macaques (Macaca mulatta). AB - BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis. RESULTS: We surveyed the 3' end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of 661 SNPs, 457 of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs. Of those, 38 SNPs were confirmed as being population-specific. CONCLUSION: This study demonstrates that the 3' end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs. These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations. PMID- 17286859 TI - Dissecting the determinants of depressive disorders outcome: an in depth analysis of two clinical cases. AB - Clinicians face everyday the complexity of depression. Available pharmacotherapies and psychotherapies improve patients suffering in a large part of subjects, however up to half of patients do not respond to treatment. Clinicians may forecast to a good extent if a given patient will respond or not, based on a number of data and sensations that emerge from face to face assessment. Conversely, clinical predictors of non response emerging from literature are largely unsatisfactory. Here we try to fill this gap, suggesting a comprehensive assessment of patients that may overcome the limitation of standardized assessments and detecting the factors that plausibly contribute to so marked differences in depressive disorders outcome. For this aim we present and discuss two clinical cases. Mr. A was an industrial manager who came to psychiatric evaluation with a severe depressive episode. His employment was demanding and the depressive episode undermined his capacity to manage it. Based on standardized assessment, Mr. A condition appeared severe and potentially dramatic. Mrs. B was a housewife who came to psychiatric evaluation with a moderate depressive episode. Literature predictors would suggest Mrs. B state as associated with a more favourable outcome. However the clinician impression was not converging with the standardized assessment and in fact the outcome will reverse the prediction based on the initial formal standard evaluation. Although the present report is based on two clinical cases and no generalizability is possible, a more detailed analysis of personality, temperament, defense mechanisms, self esteem, intelligence and social adjustment may allow to formalize the clinical impressions used by clinicians for biologic and pharmacologic studies. PMID- 17286861 TI - Ranked Adjusted Rand: integrating distance and partition information in a measure of clustering agreement. AB - BACKGROUND: Biological information is commonly used to cluster or classify entities of interest such as genes, conditions, species or samples. However, different sources of data can be used to classify the same set of entities and methods allowing the comparison of the performance of two data sources or the determination of how well a given classification agrees with another are frequently needed, especially in the absence of a universally accepted "gold standard" classification. RESULTS: Here, we describe a novel measure--the Ranked Adjusted Rand (RAR) index. RAR differs from existing methods by evaluating the extent of agreement between any two groupings, taking into account the intercluster distances. This characteristic is relevant to evaluate cases of pairs of entities grouped in the same cluster by one method and separated by another. The latter method may assign them to close neighbour clusters or, on the contrary, to clusters that are far apart from each other. RAR is applicable even when intercluster distance information is absent for both or one of the groupings. In the first case, RAR is equal to its predecessor, Adjusted Rand (HA) index. Artificially designed clusterings were used to demonstrate situations in which only RAR was able to detect differences in the grouping patterns. A study with larger simulated clusterings ensured that in realistic conditions, RAR is effectively integrating distance and partition information. The new method was applied to biological examples to compare 1) two microbial typing methods, 2) two gene regulatory network distances and 3) microarray gene expression data with pathway information. In the first application, one of the methods does not provide intercluster distances while the other originated a hierarchical clustering. RAR proved to be more sensitive than HA in the choice of a threshold for defining clusters in the hierarchical method that maximizes agreement between the results of both methods. CONCLUSION: RAR has its major advantage in combining cluster distance and partition information, while the previously available methods used only the latter. RAR should be used in the research problems were HA was previously used, because in the absence of inter cluster distance effects it is an equally effective measure, and in the presence of distance effects it is a more complete one. PMID- 17286862 TI - A gene-based radiation hybrid map of the gilthead sea bream Sparus aurata refines and exploits conserved synteny with Tetraodon nigroviridis. AB - BACKGROUND: Comparative teleost studies are of great interest since they are important in aquaculture and in evolutionary issues. Comparing genomes of fully sequenced model fish species with those of farmed fish species through comparative mapping offers shortcuts for quantitative trait loci (QTL) detections and for studying genome evolution through the identification of regions of conserved synteny in teleosts. Here a comparative mapping study is presented by radiation hybrid (RH) mapping genes of the gilthead sea bream Sparus aurata, a non-model teleost fish of commercial and evolutionary interest, as it represents the worldwide distributed species-rich family of Sparidae. RESULTS: An additional 74 microsatellite markers and 428 gene-based markers appropriate for comparative mapping studies were mapped on the existing RH map of Sparus aurata. The anchoring of the RH map to the genetic linkage map resulted in 24 groups matching the karyotype of Sparus aurata. Homologous sequences to Tetraodon were identified for 301 of the gene-based markers positioned on the RH map of Sparus aurata. Comparison between Sparus aurata RH groups and Tetraodon chromosomes (karyotype of Tetraodon consists of 21 chromosomes) in this study reveals an unambiguous one to-one relationship suggesting that three Tetraodon chromosomes correspond to six Sparus aurata radiation hybrid groups. The exploitation of this conserved synteny relationship is furthermore demonstrated by in silico mapping of gilthead sea bream expressed sequence tags (EST) that give a significant similarity hit to Tetraodon. CONCLUSION: The addition of primarily gene-based markers increased substantially the density of the existing RH map and facilitated comparative analysis. The anchoring of this gene-based radiation hybrid map to the genome maps of model species broadened the pool of candidate genes that mainly control growth, disease resistance, sex determination and reversal, reproduction as well as environmental tolerance in this species, all traits of great importance for QTL mapping and marker assisted selection. Furthermore this comparative mapping approach will facilitate to give insights into chromosome evolution and into the genetic make up of the gilthead sea bream. PMID- 17286863 TI - Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2. AB - BACKGROUND: The mechanisms underlying protein function and associated conformational change are dominated by a series of local entropy fluctuations affecting the global structure yet are mediated by only a few key residues. Transitional Dynamic Analysis (TDA) is a new method to detect these changes in local protein flexibility between different conformations arising from, for example, ligand binding. Additionally, Positional Impact Vertex for Entropy Transfer (PIVET) uses TDA to identify important residue contact changes that have a large impact on global fluctuation. We demonstrate the utility of these methods for Cyclin-dependent kinase 2 (CDK2), a system with crystal structures of this protein in multiple functionally relevant conformations and experimental data revealing the importance of local fluctuation changes for protein function. RESULTS: TDA and PIVET successfully identified select residues that are responsible for conformation specific regional fluctuation in the activation cycle of Cyclin Dependent Kinase 2 (CDK2). The detected local changes in protein flexibility have been experimentally confirmed to be essential for the regulation and function of the kinase. The methodologies also highlighted possible errors in previous molecular dynamic simulations that need to be resolved in order to understand this key player in cell cycle regulation. Finally, the use of entropy compensation as a possible allosteric mechanism for protein function is reported for CDK2. CONCLUSION: The methodologies embodied in TDA and PIVET provide a quick approach to identify local fluctuation change important for protein function and residue contacts that contributes to these changes. Further, these approaches can be used to check for possible errors in protein dynamic simulations and have the potential to facilitate a better understanding of the contribution of entropy to protein allostery and function. PMID- 17286864 TI - Patterns of gene recombination shape var gene repertoires in Plasmodium falciparum: comparisons of geographically diverse isolates. AB - BACKGROUND: Var genes encode a family of virulence factors known as PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) which are responsible for both antigenic variation and cytoadherence of infected erythrocytes. Although these molecules play a central role in malaria pathogenesis, the mechanisms generating variant antigen diversification are poorly understood. To investigate var gene evolution, we compared the variant antigen repertoires from three geographically diverse parasite isolates: the 3D7 genome reference isolate; the recently sequenced HB3 isolate; and the IT4/25/5 (IT4) parasite isolate which retains the capacity to cytoadhere in vitro and in vivo. RESULTS: These comparisons revealed that only two var genes (var1csa and var2csa) are conserved in all three isolates and one var gene (Type 3 var) has homologs in IT4 and 3D7. While the remaining 50 plus genes in each isolate are highly divergent most can be classified into the three previously defined major groups (A, B, and C) on the basis of 5' flanking sequence and chromosome location. Repertoire-wide sequence comparisons suggest that the conserved homologs are evolving separately from other var genes and that genes in group A have diverged from other groups. CONCLUSION: These findings support the existence of a var gene recombination hierarchy that restricts recombination possibilities and has a central role in the functional and immunological adaptation of var genes. PMID- 17286866 TI - Rev-dependent lentiviral expression vector. AB - BACKGROUND: HIV-responsive expression vectors are all based on the HIV promoter, the long terminal repeat (LTR). While responsive to an early HIV protein, Tat, the LTR is also responsive to cellular activation states and to the local chromatin activity where the integration has occurred. This can result in high HIV-independent activity, and has restricted the use of LTR-based reporter vectors to cloned cells, where aberrantly high expressing (HIV-negative) cells can be eliminated. Enhancements in specificity would increase opportunities for expression vector use in detection of HIV as well as in experimental gene expression in HIV-infected cells. RESULTS: We have constructed an expression vector that possesses, in addition to the Tat-responsive LTR, numerous HIV DNA sequences that include the Rev-response element and HIV splicing sites that are efficiently used in human cells. It also contains a reading frame that is removed by cellular splicing activity in the absence of HIV Rev. The vector was incorporated into a lentiviral reporter virus, permitting detection of replicating HIV in living cell populations. The activity of the vector was measured by expression of green fluorescence protein (GFP) reporter and by PCR of reporter transcript following HIV infection. The vector displayed full HIV dependency. CONCLUSION: As with the earlier developed Tat-dependent expression vectors, the Rev system described here is an exploitation of an evolved HIV process. The inclusion of Rev-dependency renders the LTR-based expression vector highly dependent on the presence of replicating HIV. The application of this vector as reported here, an HIV-dependent reporter virus, offers a novel alternative approach to existing methods, in situ PCR or HIV antigen staining, to identify HIV-positive cells. The vector permits examination of living cells, can express any gene for basic or clinical experimentation, and as a pseudo-typed lentivirus has access to most cell types and tissues. PMID- 17286865 TI - WeederH: an algorithm for finding conserved regulatory motifs and regions in homologous sequences. AB - BACKGROUND: This work addresses the problem of detecting conserved transcription factor binding sites and in general regulatory regions through the analysis of sequences from homologous genes, an approach that is becoming more and more widely used given the ever increasing amount of genomic data available. RESULTS: We present an algorithm that identifies conserved transcription factor binding sites in a given sequence by comparing it to one or more homologs, adapting a framework we previously introduced for the discovery of sites in sequences from co-regulated genes. Differently from the most commonly used methods, the approach we present does not need or compute an alignment of the sequences investigated, nor resorts to descriptors of the binding specificity of known transcription factors. The main novel idea we introduce is a relative measure of conservation, assuming that true functional elements should present a higher level of conservation with respect to the rest of the sequence surrounding them. We present tests where we applied the algorithm to the identification of conserved annotated sites in homologous promoters, as well as in distal regions like enhancers. CONCLUSION: Results of the tests show how the algorithm can provide fast and reliable predictions of conserved transcription factor binding sites regulating the transcription of a gene, with better performances than other available methods for the same task. We also show examples on how the algorithm can be successfully employed when promoter annotations of the genes investigated are missing, or when regulatory sites and regions are located far away from the genes. PMID- 17286867 TI - APP-BP1 inhibits Abeta42 levels by interacting with Presenilin-1. AB - BACKGROUND: The beta-amyloid precursor protein (APP) is sequentially cleaved by the beta- and then gamma-secretase to generate the amyloid beta-peptides Abeta40 and Abeta42. Increased Abeta42/Abeta40 ratios trigger amyloid plaque formations in Alzheimer's disease (AD). APP binds to APP-BP1, but the biological consequence is not well understood. RESULTS: We report that when the endogenous APP-BP1 was suppressed by small interfering RNAs (siRNAs), cell-associated Abeta42 was dramatically increased in APP695 expressing primary neurons. The accumulation of Abeta42 was accompanied by significant increases in APP and APP-CTF in APP-BP1 siRNA expressing neurons. In contrast, APP-BP1 overexpression in primary neurons significantly decreased the levels of Abeta and endogenous APP but not APLPs. We also investigated the potential mechanism of APP-BP1-mediated APP processing. APP BP1 co-precipitated with Presenilin-1 (PS1) in native rat brain extracts, co migrated with the gamma-secretase components in brain membrane extracts in glycerol gradient centrifugation, and colocalized in primary neurons. Further, the endogenous PS1-CTF was significantly downregulated by APP-BP1 expression. CONCLUSION: Our data suggest that APP-BP1 may inhibit Abeta42 production by interacting with PS1 under physiological conditions. PMID- 17286868 TI - Examining correlates of treatment satisfaction for injectable insulin in type 2 diabetes: lessons learned from a clinical trial comparing biphasic and basal analogues. AB - BACKGROUND: Successfully managing diabetes is a complex process that includes addressing issues of drug efficacy, safety and treatment satisfaction. Additionally, the combined impact of patient/disease characteristics and treatment outcomes on treatment satisfaction is not well understood. The purpose of this study was to examine the impact of age, weight, gender, co-morbid conditions, diabetes history, treatment burden, efficacy (HbA1c) and side effects (weight gain, hypoglycemic events) on patients' appraisal of treatment satisfaction using linear regression models. METHODS: Data from a multi-center, randomized clinical trial comparing the efficacy/safety of biphasic insulin aspart 70/30 (BIAsp 70/30) vs. glargine (Glar) among insulin naive type 2 patients were analyzed. Subjects were between ages 18-75, with baseline HbA1c > 8% and BMI < or = 40 kg/m2 (N = 233). Treatment satisfaction was assessed by the Insulin Treatment Satisfaction Questionnaire (ITSQ). RESULTS: When factors were examined independently, multiple significant relationships (age, co-morbidity, hypoglycemic events, and weight gain) with overall and/or domains of treatment satisfaction were found. However, when all significant relationships were examined together, only neuropathy, treatment efficacy, and number of hypoglycemic events maintained their previous significance. CONCLUSION: By examining predictors independently, significant relationships were identified. However, not all findings remained significant when examined in combination with each other. Thus, to more accurately characterize the impact of factors on treatment satisfaction, a more comprehensive approach may be necessary. By improving patient treatment satisfaction, the efficacy of treatments, as well as critical treatment outcomes such as compliance and cost of care should be improved. PMID- 17286870 TI - Interactions of viruses in Cowpea: effects on growth and yield parameters. AB - The study was carried out to investigate the effects of inoculating three cowpea cultivars: "OLO II", "OLOYIN" and IT86D-719 with three unrelated viruses: Cowpea aphid-borne mosaic virus (CABMV), genus Potyvirus, Cowpea mottle virus (CMeV), genus Carmovirus and Southern bean mosaic virus (SBMV), genus Sobemovirus singly and in mixture on growth and yield of cultivars at 10 and 30 days after planting (DAP). Generally, the growth and yield of the buffer inoculated control plants were significantly higher than those of the virus inoculated plants. Inoculation of plants at an early age of 10 DAP resulted in more severe effect than inoculations at a later stage of 30 DAP. The average values of plant height and number of leaves produced by plants inoculated 30 DAP were higher than those produced by plants inoculated 10 DAP. Most of the plants inoculated 10 DAP died and did not produce seeds. However, " OLOYIN" cultivar was most tolerant and produced reasonable yields when infected 30 DAP. The effect of single viruses on growth and yield of cultivars showed that CABMV caused more severe effects in IT86D-719, SBMV had the greatest effect on "OLO II" while CMeV induced the greatest effect on "OLOYIN". Yield was greatly reduced in double infections involving CABMV in combination with either CMeV or SBMV in "OLOYIN" and "OLO II", however, there was complete loss in yield of IT86D-719. Triple infection led to complete yield loss in all the three cultivars. PMID- 17286869 TI - Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer. AB - BACKGROUND: YKL-40 has been implicated as a mediator of collagen synthesis and extracellular matrix re-modeling as well as mitogenesis. Elevated serum levels of YKL-40 have been associated with worse survival in a variety of malignancies including breast cancer. We wished to determine if immunohistochemically detected expression had prognostic implications in breast cancer. METHODS: A prospectively collected database of breast cancer patients treated at the University Hospital of Newark was used for analysis. Immunohistochemistry was performed on archived tumor tissue from 109 patients for whom full clinical information and follow up was available. RESULTS: YKL-40 expression was noted in 37 patients (34%). YKL-40 immunoreactivity significantly correlated with larger tumor size, poorer tumor differentiation, and a greater likelihood of being estrogen and/or progesterone receptor negative. No significant correlation was demonstrated between YKL-40 status and nodal stage. At a mean follow up of 3.2 years, disease-free survival was significantly worse in the subset of patients whose tumors demonstrated YKL 40 expression compared to the non-expressors. In multivariate analysis, YKL-40 status was independent of T-stage and N-stage in predicting disease recurrence. CONCLUSION: Immunoreactivity for YKL-40 was a significant predictor of breast cancer relapse in this subset of patients. This was independent of T or N-stage and suggests that tumor immunohistochemistry for this protein may be a valuable prognostic marker in breast cancer. PMID- 17286871 TI - Continued spread of HIV among injecting drug users in southern Sichuan Province, China. AB - OBJECTIVE: To estimate HIV prevalence among injecting drug users (IDUs) in a drug trafficking city in southwest Sichuan Province, China. METHODS: A total of 314 IDUs was invited to participate in the cross-sectional survey in 2004 through community outreach recruitment and peer referrals. Blood sample was taken for HIV antibody testing and a structured questionnaire was administered to collect information on socio-demographics, drug using and sexual behaviors. RESULTS: HIV prevalence among IDUs was 17.8% (56/314), about one half higher than that in previous survey in 2002 (11.3%, 43/379). Yi and other minority ethnicity (Odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.8; P < 0.001), and total times of sharing injecting equipment 1-9 times versus none, OR, 2.7; 95% CI 1.2 6.2; P = 0.02; and > or = 10 times versus none, OR, 7.5; 95% CI, 3.2-17.7; P < 0.001) were independent risk factors for HIV infection. CONCLUSION: IDUs with high prevalence rates of HIV and equipment sharing behavior in the drug trafficking city may serve a source for further spread of HIV to other areas in China. The increasing trend of HIV epidemic among IDUs underscores the urgency of scaling up interventions. PMID- 17286872 TI - Hon-yaku: a biology-driven Bayesian methodology for identifying translation initiation sites in prokaryotes. AB - BACKGROUND: Computational prediction methods are currently used to identify genes in prokaryote genomes. However, identification of the correct translation initiation sites remains a difficult task. Accurate translation initiation sites (TISs) are important not only for the annotation of unknown proteins but also for the prediction of operons, promoters, and small non-coding RNA genes, as this typically makes use of the intergenic distance. A further problem is that most existing methods are optimized for Escherichia coli data sets; applying these methods to newly sequenced bacterial genomes may not result in an equivalent level of accuracy. RESULTS: Based on a biological representation of the translation process, we applied Bayesian statistics to create a score function for predicting translation initiation sites. In contrast to existing programs, our combination of methods uses supervised learning to optimally use the set of known translation initiation sites. We combined the Ribosome Binding Site (RBS) sequence, the distance between the translation initiation site and the RBS sequence, the base composition of the start codon, the nucleotide composition (A rich sequences) following start codons, and the expected distribution of the protein length in a Bayesian scoring function. To further increase the prediction accuracy, we also took into account the operon orientation. The outcome of the procedure achieved a prediction accuracy of 93.2% in 858 E. coli genes from the EcoGene data set and 92.7% accuracy in a data set of 1243 Bacillus subtilis 'non y' genes. We confirmed the performance in the GC-rich Gamma-Proteobacteria Herminiimonas arsenicoxydans, Pseudomonas aeruginosa, and Burkholderia pseudomallei K96243. CONCLUSION: Hon-yaku, being based on a careful choice of elements important in translation, improved the prediction accuracy in B. subtilis data sets and other bacteria except for E. coli. We believe that most remaining mispredictions are due to atypical ribosomal binding sequences used in specific translation control processes, or likely errors in the training data sets. PMID- 17286875 TI - The bilingual effect on Boston Naming Test performance. AB - The present study aimed to determine how older bilingual subjects' naming performance is affected by their knowledge of two languages. Twenty-nine aging (mean age = 74.0; SD = 7.1) Spanish-English bilinguals were asked to name all pictures in the Boston Naming Test (BNT) first in their dominant language and then in their less-dominant language. Bilinguals with similar naming scores in each language, or relatively balanced bilinguals, named more pictures correctly when credited for producing a correct name in either language. Balanced bilinguals also named fewer pictures in their dominant language than unbalanced bilinguals, and named more pictures correctly in both languages if the pictures had cognate names (e.g., dart is dardo in Spanish). Unbalanced bilinguals did not benefit from the alternative (either-language) scoring procedure and showed cognate effects only in their nondominant language. These findings may help to guide the interpretation of neuropsychological data for the purpose of determining cognitive status in older bilinguals and can be used to develop models of bilingual language processing. Bilinguals' ability to name pictures reflects their experience with word forms in both languages. PMID- 17286873 TI - The spectrum of Apert syndrome: phenotype, particularities in orthodontic treatment, and characteristics of orthognathic surgery. AB - In the PubMed accessible literature, information on the characteristics of interdisciplinary orthodontic and surgical treatment of patients with Apert syndrome is rare. The aim of the present article is threefold: (1) to show the spectrum of the phenotype, in order (2) to elucidate the scope of hindrances to orthodontic treatment, and (3) to demonstrate the problems of surgery and interdisciplinary approach.Children and adolescents who were born in 1985 or later, who were diagnosed with Apert syndrome, and who sought consultation or treatment at the Departments of Orthodontics or Craniomaxillofacial Surgery at the Dental School of the University Hospital of Munster (n = 22; 9 male, 13 female) were screened. Exemplarily, three of these patients (2 male, 1 female), seeking interdisciplinary (both orthodontic and surgical treatment) are presented. Orthodontic treatment before surgery was performed by one experienced orthodontist (AH), and orthognathic surgery was performed by one experienced surgeon (UJ), who diagnosed the syndrome according to the criteria listed in OMIM. In the sagittal plane, the patients suffered from a mild to a very severe Angle Class III malocclusion, which was sometimes compensated by the inclination of the lower incisors; in the vertical dimension from an open bite; and transversally from a single tooth in crossbite to a circular crossbite. All patients showed dentitio tarda, some impaction, partial eruption, idopathic root resorption, transposition or other aberrations in the position of the tooth germs, and severe crowding, with sometimes parallel molar tooth buds in each quarter of the upper jaw.Because of the severity of malocclusion, orthodontic treatment needed to be performed with fixed appliances, and mainly with superelastic wires. The therapy was hampered with respect to positioning of bands and brackets because of incomplete tooth eruption, dense gingiva, and mucopolysaccharide ridges. Some teeth did not move, or moved insufficiently (especially with respect to rotations and torque) irrespective of surgical procedures or orthodontic mechanics and materials applied, and without prognostic factors indicating these problems. Establishing occlusal contact of all teeth was difficult. Tooth movement was generally retarded, increasing the duration of orthodontic treatment. Planning of extractions was different from that of patients without this syndrome.In one patient, the sole surgical procedure after orthodontic treatment with fixed appliances in the maxilla and mandible was a genioplasty. Most patients needed two- jaw surgery (bilateral sagittal split osteotomy [BSSO] with mandibular setback and distraction in the maxilla). During the period of distraction, the orthodontist guided the maxilla into final position by means of bite planes and intermaxillary elastics.To our knowledge, this is the first article in the PubMed accessible literature describing the problems with respect to interdisciplinary orthodontic and surgical procedures. Although the treatment results are not perfect, patients undergoing these procedures benefit esthetically to a high degree.Patients need to be informed with respect to the different kinds of extractions that need to be performed, the increased treatment time, and the results, which may be reached using realistic expectations. PMID- 17286876 TI - Bilingualism and naming: implications for cognitive assessment. AB - The article by Gollan, Fennema-Notestine, Montoya, and Jernigan (2007, this issue) raises important issues about the, effects of bilingualism on naming test performance in older adults. In particular, proficiency in their two languages determines the ability with which older bilingual adults can name pictures in each of those languages. This observation is important if cognitive status is inferred from naming performance. In this commentary we largely endorse the arguments made by Gollan and colleagues, although we point to some limitations in their experimental design. PMID- 17286877 TI - Performance on the Boston Naming Test in English-Spanish bilingual older adults: some considerations. AB - Gollan, Fennema-Notestine, Montoya, and Jernigan (this issue) present a timely and clinically relevant study that examines the impact of bilingualism on the performance on the Boston Naming Test in older adults. In light of the methodology employed, we weigh different potential interpretations of the findings and make recommendations for future studies. PMID- 17286879 TI - Preserved memory monitoring but impaired memory control during episodic encoding in patients with schizophrenia. AB - Metamemory awareness refers to the ability to monitor and control how well information is processed depending on the loads and needs of the task at hand. There is some evidence that metamemory functions are impaired in schizophrenia at the time of memory retrieval. This study investigated whether patients with schizophrenia exhibit metamemory abnormalities during the encoding of new information. The frequency of item presentation was varied. Both memory control and memory monitoring were assessed using study-time allocation and Judgments of Learning (JOL), respectively. Repeated items were recalled better by both groups, but memory performance was lower in patients than controls. Patients' behavior patterns were abnormal in terms of the study-time allocated for each item according to presentation frequency. Patients' JOLs were lower than those of controls but remained sensitive to item repetition. Patients' predictive values on memory accuracy were no different to those measured in controls. In addition, none of the patients reported using efficient strategies to help memorize target items. The results show a dissociation between memory control, which was impaired, and memory monitoring, which was spared, in patients with schizophrenia during encoding of new information. PMID- 17286880 TI - Do reading tests measure the same construct in multiethnic and multilingual older persons? AB - A critical focus of neuropsychological research is to identify unbiased ways to compare heterogeneous groups on background variables relevant to neuropsychological performance. Whereas recent work has pointed to single word reading as a less culturally biased measure of educational experience than years of education, the extent to which reading score captures a broad range of educational experience and does so consistently across ethnic and language groups is unknown. The current study evaluated reading in relation to years of education in English-speaking Whites, Blacks, and Hispanics, and Spanish-speaking Hispanic older persons (n = 342). Consistent with previous work, reading scores at each grade level were lower in English speaking ethnic minorities than in Whites, supporting the idea that variables related to lifetime educational experience are often confounded with ethnicity. Standardized reading scores were highest in the Spanish speakers; however, interpretation of this difference is limited because scores were necessarily derived using separate normative samples. Importantly, the slopes of reading score by years of education were comparable across all groups. That is, reading scores rose consistently with years of education independently of ethnicity or language, suggesting that such scores can be treated comparably for theoretical and statistical purposes in multiethnic and multilingual samples. PMID- 17286881 TI - A longitudinal study of language decline in Alzheimer's disease and frontotemporal dementia. AB - Language decline is usually the fastest and predominant change in primary progressive aphasia (PPA). In Alzheimer's disease (AD), it is usually associated with global cognitive deficits. Decreased speech output, reduced conversational initiation, echolalia, and changes in the pragmatics of conversation are seen in the behavioral variant of frontotemporal dementia (FTD-bv), however, the evolution of language disturbance in FTD-bv patients is rarely examined systematically with a standardized language battery. We aimed to longitudinally track the nature of language change in FTD-bv, PPA, and AD using a standardized measure of language functioning. We also explored the nature of language deficits between semantic dementia (SD) patients and the fluent subgroup of PPA patients. The Western Aphasia Battery was administered to 105 AD, 20 FTD-bv, 54 PPA, and 10 SD patients on 2 occasions with approximately 1 year between assessments. Ninety nine of these patients were examined an additional year. FTD-bv and PPA patients showed a faster language decline than AD patients. The eventual overlap in language functioning in FTD-bv and PPA suggests that these syndromes belong to the same spectrum of disorders. In conclusion, longitudinal language assessment provides us with a unique understanding of the evolution and progression of language deterioration in various dementias. PMID- 17286882 TI - Motor and gestural performance in children with autism spectrum disorders, developmental coordination disorder, and/or attention deficit hyperactivity disorder. AB - Motor and gestural skills of children with autism spectrum disorders (ASD), developmental coordination disorder (DCD), and/or attention deficit hyperactivity disorder (ADHD) were investigated. A total of 49 children with ASD, 46 children with DCD, 38 children with DCD+ADHD, 27 children with ADHD, and 78 typically developing control children participated. Motor skills were assessed with the Bruininks-Oseretsky Test of Motor Proficiency Short Form, and gestural skills were assessed using a test that required children to produce meaningful gestures to command and imitation. Children with ASD, DCD, and DCD+ADHD were significantly impaired on motor coordination skills; however, only children with ASD showed a generalized impairment in gestural performance. Examination of types of gestural errors revealed that children with ASD made significantly more incorrect action and orientation errors to command, and significantly more orientation and distortion errors to imitation than children with DCD, DCD+ADHD, ADHD, and typically developing control children. These findings suggest that gestural impairments displayed by the children with ASD were not solely attributable to deficits in motor coordination skills. PMID- 17286883 TI - Predictors of cognitive function in candidates for coronary artery bypass graft surgery. AB - Candidates for coronary artery bypass graft surgery have been found to exhibit reduced cognitive function prior to surgery. However, little is known regarding the factors that are associated with pre-bypass cognitive function. A battery of neuropsychological tests was administered to a group of patients listed for bypass surgery (n = 109). Medical, sociodemographic and emotional predictors of cognitive function were investigated using structural equation modeling. Medical factors, namely history of hypertension and low ejection fraction, significantly predicted reduced cognitive function, as did several sociodemographic characteristics, namely older age, less education, non-English speaking background, manual occupation, and male gender. One emotional variable, confusion and bewilderment, was also a significant predictor whereas anxiety and depression were not. When significant predictors from the three sets of variables were included in a combined model, three of the five sociodemographic characteristics, namely age, non-English speaking background and occupation, and the two medical factors remained significant. Apart from sociodemographic characteristics, medical factors such as a history of hypertension and low ejection fraction significantly predicted reduced cognitive function in bypass candidates prior to surgery. PMID- 17286885 TI - Inhibition of inappropriate responses is preserved in the Think-No-Think and impaired in the random number generation tasks in schizophrenia. AB - We examined the ability of 23 schizophrenia patients and 24 healthy controls to exert intentional inhibition of prepotent responses in the Think-No-Think (TNT) paired-associate learning paradigm (Anderson & Green, 2001). TNT manipulates the frequency (1, 8, 16 times) of intentional attempts to suppress (inhibit) some target words and to respond to most cue words. Following a TNT practice-phase, recall of suppressed words was tested in two ways, using the same cue words initially learned, and the category name plus letter-stem of the target words. Inhibition of prepotent responses was also examined in a random number generation (RNG) task. In TNT, speed results showed longer reaction times after 16 suppress attempts in patients, not in controls, reflecting increased difficulty with retrieving the memory traces of the overridden items. In accuracy, no between groups differences were evidenced, and overall patterns replicated those of Anderson & Green. In RNG, patients produced more stereotyped responses and ascending and descending counting than controls, pointing to on-line failures to inhibit prepotent responses. These findings suggest that schizophrenia patients' difficulties to inhibit prepotent responses appear specific, not widespread, the intentional inhibition addressed in TNT being preserved, and on-line inhibition in RNG being impaired. PMID- 17286884 TI - Testing neuropsychological hypotheses for cognitive deficits in psychopathic criminals: a study of global-local processing. AB - Competing hypotheses about neuropsychological mechanisms underlying psychopathy are seldom examined in the same study. We tested the left hemisphere activation hypothesis and the response modulation hypothesis of psychopathy in 172 inmates completing a global-local processing task under local bias, global bias, and neutral conditions. Consistent with the left hemisphere activation hypothesis, planned comparisons showed that psychopathic inmates classified local targets more slowly than nonpsychopathic inmates in a local bias condition and exhibited a trend toward similar deficits for global targets in this condition. However, contrary to the response modulation hypothesis, psychopaths were no slower to respond to local targets in a global bias condition. Because psychopathic inmates were not generally slower to respond to local targets, results are also not consistent with a general left hemisphere dysfunction account. Correlational analyses also indicated deficits specific to conditions presenting most targets at the local level initially. Implications for neuropsychological conceptualizations of psychopathy are considered. PMID- 17286886 TI - A detailed profile of cognitive dysfunction and its relation to psychological distress in patients with type 2 diabetes mellitus. AB - Type 2 diabetes mellitus (DM2) is a common metabolic disorder. DM2 is associated with cognitive impairments, and with depressive symptoms, which occur in about one third of patients. In the current study we compared the cognitive profile and psychological well-being of 119 patients with DM2 (mean age: 66 +/- 6; mean duration: 9 +/- 6 years) with 55 age and education matched-control participants. Groups were compared on cognitive performance in five major cognitive domains, psychological wellbeing [assessed by Symptom Checklist (SCL)-90-R and the Beck Depression Inventory (BDI-II)] and abnormalities on brain MRI. We hypothesized an interrelationship between cognition, MRI abnormalities, and psychological well being. DM2 patients performed significantly worse than controls on cognitive tasks, especially on tasks that required more mental efficiency, although the differences were modest (effect sizes Cohen d < .6). We speculate that DM2 patients have a diminished ability to efficiently process unstructured information. Patients with DM2 had significantly higher scores on the SCL-90-R (p < .001) and on the BDI-II (p < .001) and worse MRI ratings than controls, but psychological distress did not correlate with cognition, MRI ratings or biomedical characteristics. Contrary to our hypothesis, cognitive disturbances and psychological distress thus seem independent symptoms of the same disease. PMID- 17286887 TI - Self-regulation as a mediator of the effects of childhood traumatic brain injury on social and behavioral functioning. AB - This study builds on our earlier investigation (see Ganesalingam et al., 2006). We showed previously that children with moderate to severe traumatic brain injuries (TBI) had poorer self-regulation and social and behavioral functioning than their uninjured peers and that self-regulation predicted significant variance in parent- and teacher-rated social and behavioral outcomes, regardless of the presence or absence of TBI. In this study, we examine self-regulation as a mediator of the relationship between TBI and the outcomes. Participants included 65 children with moderate to severe TBI and 65 children without TBI matched for age and gender. Participants were between 6 and 11 years of age. Children completed an assessment of cognitive, emotional, and behavioral self-regulation, and social and behavioral functioning. Mediation was assessed using a bootstrapping approach (a relatively novel statistical method for assessing specific indirect effects in models with multiple mediators). Analyses indicated that, after controlling for socioeconomic status (SES), aspects of self regulation accounted for individual variation in the outcomes, and acted as a significant mediator of the effects of TBI on the outcomes. Self-regulatory deficits may reflect the relative vulnerability of the prefrontal cortex to TBI and may help account for post-injury difficulties in social and behavioral functioning. PMID- 17286888 TI - Prospective, declarative, and nondeclarative memory in young adults with spina bifida. AB - The consequences of congenital brain disorders for adult cognitive function are poorly understood. We studied different forms of memory in 29 young adults with spina bifida meningomyelocele (SBM), a common and severely disabling neural tube defect. Nondeclarative and semantic memory functions were intact. Working memory was intact with low maintenance and manipulation requirements, but impaired on tasks demanding high information maintenance or manipulation load. Prospective memory for intentions to be executed in the future was impaired. Immediate and delayed episodic memory were poor. Memory deficits were exacerbated by an increased number of lifetime shunt revisions, a marker for unstable hydrocephalus. Memory status was positively correlated with functional independence, an important component of quality of life. PMID- 17286889 TI - Executive functions and adaptive functioning in young adult attention deficit/hyperactivity disorder. AB - Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in occupational, social, and educational functioning in adults. This study examined relations of adaptive impairment to ADHD symptom domains (inattentive disorganized and hyperactive-impulsive) and to deficits in executive functioning (EF) in 195 well-characterized adults (105 ADHD, 90 non-ADHD, between ages 18 and 37). Participants completed a battery of EF measures as well as assessments of adaptive functioning. Confirmatory factor analyses were used to validate latent factors for adaptive functioning and EF. In a measurement model, weaker EF was associated with poorer adaptive functioning (r = -.30). When multi-informant composite variables for current inattentive-disorganized and hyperactive impulsive ADHD symptoms were included in the structural model, EF no longer predicted adaptive functioning. While both symptom composites were similarly related to EF (inattentive-disorganized r = .36; hyperactive-impulsive r = .29), inattentive-disorganized symptoms accounted for more variance in adaptive functioning (67.2% vs. 3.6%). Furthermore, for retrospectively reported childhood symptoms of ADHD, only the inattentive-disorganized symptom domain was related to EF or adaptive impairment. These results suggest that, in adults with ADHD, inattentive-disorganized symptoms may be the primary contributor to key aspects of poorer adaptive function and may be the behavioral path through which EF deficits lead to adaptive impairment. PMID- 17286890 TI - Autobiographical memory of adolescence and early adulthood events: an investigation in schizophrenia. AB - The reminiscence bump corresponds to a marked increase in autobiographical memories of events that occurred when normal people were aged 10 to 30 years, a critical period for the formation of identity. The reminiscence bump was studied in 27 patients diagnosed with schizophrenia and 27 control participants. They were asked to recall 20 specific autobiographical events that had occurred during their lifetime and to indicate the subjective states of awareness associated with the recalled memories using the Remember/Know procedure. Finally, participants were asked to state whether recalled memories related to private or public events. Patients diagnosed with schizophrenia recalled less specific memories than controls and exhibited an earlier reminiscence bump. They recalled more public, and less private events than controls, and they gave fewer Remember responses. The reminiscence bump peaked in the 16 to 25-year period for patients and the 21 to 25-year period for controls. These findings indicate that patients diagnosed with schizophrenia exhibit an early and abnormal reminiscence bump, with an impairment of conscious recollection associated with memories highly relevant to personal identity. They suggest that schizophrenia is associated with an impairment of autobiographical memories of events that had occurred during the last stage of personal identity development. PMID- 17286891 TI - Differential impact of age on verbal memory and executive functioning in chronic kidney disease. AB - We compared aspects of verbal memory and executive functioning in 51 community dwelling persons with chronic kidney disease (CKD) and 55 healthy controls matched on age and education. Depressive symptoms were assessed with the Centre for Epidemiological Studies-Depression Scale (CES-D), and illness variables included glomerular filtration rate (GFR) and hemoglobin. Findings indicate that persons with CKD exhibited poorer performance on measures of memory (CVLT-II) and executive functioning (DKEFS Trailmaking Test B and Color-Word Interference Tests) in comparison with healthy controls. Furthermore, performance decrements were magnified in older CKD participants on measures of verbal memory and inhibition. Nearly half of CKD participants aged 61 and older exhibited significant impairments in verbal memory and inhibition in comparison to matched controls. Cognitive performance in CKD was not associated with measures of illness severity. The differences observed were not accounted for by depressive symptoms, which were only weakly associated with cognitive performance, and negatively associated with age. Findings highlight the need for further exploration of the etiologies and functional consequences of the neuropsychological presentation of CKD. PMID- 17286892 TI - Utility of California Verbal Learning Test, Second Edition, recall discriminability indices in the evaluation of traumatic brain injury. AB - The performance of 23 patients with moderate-severe traumatic brain injury on the California Verbal Learning Test, Second Edition (CVLT-II; Delis et al., 2000) was compared with that of 23 matched healthy controls to determine whether recall discriminability indices, which take into account both correct target recall and intrusive errors, would provide better diagnostic classification than traditional variables that are based exclusively on correct recall. Patients with traumatic brain injury recalled fewer correct words, and also made more intrusive errors, on CVLT-II short and long delay, free and cued recall trials (p < .02 for all variables after Stepdown Bonferroni correction). However, recall discriminability indices yielded a classification of clinical versus control participants (72%) that was not significantly different from one based on traditional variables (74%). We conclude that CVLT-II recall discriminability indices do not routinely provide an advantage over traditional variables in patients with traumatic brain injury. PMID- 17286893 TI - The impact of reading and writing skills on a visuo-motor integration task: a comparison between illiterate and literate subjects. AB - Previous studies have shown a significant association between reading skills and the performance on visuo-motor tasks. In order to clarify whether reading and writing skills modulate non-linguistic domains, we investigated the performance of two literacy groups on a visuo-motor integration task with non-linguistic stimuli. Twenty-one illiterate participants and twenty matched literate controls were included in the experiment. Subjects were instructed to use the right or the left index finger to point to and touch a randomly presented target on the right or left side of a touch screen. The results showed that the literate subjects were significantly faster in detecting and touching targets on the left compared to the right side of the screen. In contrast, the presentation side did not affect the performance of the illiterate group. These results lend support to the idea that having acquired reading and writing skills, and thus a preferred left to-right reading direction, influences visual scanning. PMID- 17286894 TI - Memory for intentions in amnestic mild cognitive impairment: time- and event based prospective memory. AB - Amnestic mild cognitive impairment (aMCI) is associated with neuropathological changes in medial-temporal and frontal-system structures. By definition, retrospective memory is mildly impaired in aMCI. We examined whether prospective memory (PM) is also impaired, in particular time-based PM, which requires considerable self-initiation and inhibition. We administered time- and event based PM tasks to 42 healthy older adults, 45 individuals with aMCI, and 24 individuals with Alzheimer's disease (AD). The healthy group performed better than the aMCI group, and the aMCI group performed better than the AD group on both PM tasks. Importantly, the aMCI group performed more poorly on the time- than event-based task, whereas the other groups performed comparably on both tasks. Findings suggest that PM, particularly time-based PM, is sensitive to the earliest cognitive changes associated with aMCI, possibly reflecting decreased self-initiation, attention switching, and/or inhibition on memory tasks because of early involvement of the frontal system. PMID- 17286895 TI - Inappropriate use of covariate analysis renders meaningless results. PMID- 17286897 TI - [Expression and refolding of a HLA-A*0203-BSP fusion protein and identification of its tetramers]. AB - AIM: To optimize expression condition of HLA-A*0203 heavy chain ectodomain fused with a BirA substrate peptide (BSP) (HLA-A*0203-BSP) for E.coli BL21(DE3) transformant and to prepare a functional HLA-A*0203 tetramer loaded with an antigenic peptide derived from EBNA3(596-604) of Epstein-Barr virus (EBV). METHODS: The temperature, IPTG concentration and inductive duration of HLA-A*0203 BSP fusion protein expressed for E.coli BL21(DE3) transformant were optimized. SDS-PAGE and Western blot analyses were employed to detect the expressed fusion protein. The monomer of soluble HLA-A*0203-peptide was generated from the fusion protein by in vitro refolding of washed inclusion bodies in the presence of beta2 microglobulin (beta2m) and HLA-A*0203 restricted EBV EBNA3(596-604) peptide (SVRDRLARL, SVR). Refolded and purified monomer was then biotinylated with BirA. Following the purification of the obtained biotinylated monomer, the tetramer was formed by incubation with streptavidin-PE at a ratio of 4:1. Flow cytometry (FCM) analysis was performed to determine its binding activity with specific cytotoxic T lymphocytes (CTL). RESULTS: SDS-PAGE and Western blot showed that the optimized expression condition was overnight induction at 37 degrees C with 0.4 mmol/L IPTG. The expressed protein of about 34 kDa in the form of inclusion bodies accumulated up to about 30% of total bacterial protein under the optimized expression condition. The monomer of soluble HLA-A*0203/SVR was successfully generated and purified. Non-reducing SDS-PAGE analysis showed that the biotinylation was above 85%. HLA-A*0203/SVR tetramer was constructed by mixing the monomer with streptavidin-PE at a ratio of 4:1. FCM analysis indicated that this tetramer could bind specific CTL from HLA-A2+ donors. CONCLUSION: HLA-A*0203 BSP fusion protein was overexpressed in E.coli under the optimized condition. The tetramers of HLA-A*0203/SVR were prepared from this fusion protein and it possessed binding activity with specific CTL, which provided a powerful tool for direct visualization and quantification of specific CTL from HLA-A*0203 donors. PMID- 17286898 TI - [Effect of extracellular-signal regulated kinase 1/2 specific repressor PD98059 on murine lymphocyte proliferation]. AB - AIM: To investigate the effect of PD98059, a specific repressor of extracellular signal regulated kinase 1/2 (ERK1/2), on the proliferation of the murine lymphocytes. METHODS: Lymphocytes were isolated from lymphoid nodes of BALB/c mouse. After stained with carboxy fluorescein diacetate, succinimidyl ester(CFDA SE), the cells were stimulated with polyclonal activators, concanavalin(ConA) and phorbol 12,13-dibutyrate(PDB) plus ionomycin(Ion). The proliferation and cell cycle of lymphocytes were analyzed using flow cytometry(FCM). RESULTS: CFDA-SE staining showed that 5, 10, 20, 30 and 40 micromol/L PD98059 could significantly inhibit the proliferation of murine lymphocytes induced by ConA. The inhibitory effect was dose-dependent(r=0.985, P<0.01). The optimal concentration of 30 micromol/L PD98059 was selected and its inhibitory effect was significantly decreased with prolongation of time (P<0.01); but the inhibitory rate increased. Analysis of the cell cycle induced by ConA revealed that the cells was blocked into S and G2/M phases as the concentration of PD98059 increased. However, the cell number in sub-G0/G1 peak (apoptotic peak) had no significant change under the concentration range used. PD98059 had the similar effect on the cells treated with PDB plus Ion, but S and G2/M phases were more distinct. CONCLUSION: PD98059 can inhibit the proliferation of the murine lymphocytes and blocked them into S and G2/M phases, indicating the activation of ERK1/2 signaling pathway plays an important role in the proliferation of lymphocytes. PMID- 17286899 TI - [Inhibiton of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99]. AB - AIM: To explore the synergistic effect of MBP 68-86 and 87-99, on the inhibition of experimental autoimmune encephalomyelitis (EAE) in Lewis rat by nasal administration. METHODS: Three different MBP peptides(MBP 68-86, 87-99, and the non-encephalitogenic peptide 110-128) were synthesized and administrated nasally to Lewis rat on day-11, -10, -9, -8 and -7 prior to immunization with the guinea pig MBP (gp-MBP)+CFA, which was used to induce EAE. The protective effect on Lewis rat from EAE by the MBP peptides was evaluated. RESULTS: Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 used alone conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP induced EAE even at lower dosage than being used alone. Rats tolerized with MBP 68-86+87-99 nasally showed decreased T cell responses to MBP, reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68 86+87-99 also had abrogated MBP-reactive IFN-gamma and TNF-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive TGF-beta and IL-4 mRNA expressing cells were observed in the two groups. CONCLUSION: Nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration. PMID- 17286900 TI - [Prokaryotic expression and characterization of N-terminal truncated glycoprotein gp85 of Epstein-Barr virus]. AB - AIM: To construct a prokaryotic recombinant vector of Epstein-Barr virus (EBV) membrane protein gp85, to express the protein in E.coli and characterize the antigenicity of this non-glycosylated protein. METHODS: The BXLF2 gene coding 5' terminal truncated of EBV gp85 was amplified from the EBV strain B95-8 cell line with specific primers. After identification by the restriction digestion with Hind III and Xho I, the PCR product was inserted into the prokaryotic expression plasmid pGEX-5T and confirmed by sequencing. The constructed prokaryotic expression vector pGEX5T-85N was transformed into the competent E.coli BL21. The expressed recombinant protein gp85N was purified by affinity chromatography, characterized by Western blot, and used immunize BALB/c mice. The titer of antiserum from the immunized mice was detected by ELISA. RESULTS: Sequencing analysis revealed that the obtained truncated BXLF2 gene was identical to that published in GenBank and successfully cloned into pGEX-5T. SDS-PAGE showed that the expressed recombinant protein was partially soluble with a relative molecular mass of 45,000. ELISA results indicated that the expressed gp85N was recognized by that the anti-gp85 mAb and contiserum with high titer was obtained from the immunized mice. CONCLUSION: The obtained recombinant gp85N with an excellent antigenicity should provide preliminary data for characterization of the antibody produced by the immunized mice. PMID- 17286902 TI - [Specific cytotoxicity of CTL which was induced by DC pulsed with mannosylated antigen]. AB - AIM: To investigate the role of mannosylated tumor antigen in the course of anti tumor response. METHODS: L2 domain of HER-2/neu (ErbB2) ectodomain was expressed in E.coli, purified and mannosylated. Dendritic cells(DCs) were induced from human peripheral blood mononuclear cell by GM-CSF and IL-4. The maturation and functional capacity of DCs pulsed with mannosylated L2 (mL2) protein was investigated. RESULTS: L2 protein could induce DC maturation, which was accompanied by elevated expression of MHC and costimulatory molecules. The effect of mL2 protein on DC maturation was more remarkable than that of non-mannosylated L2 protein. Furthermore, DCs pulsed with mL2 could stimulate high tumor cell lysis by CTL. CONCLUSION: Our experiment provide the foundation for the study of new tumor vaccine by mannosylation. PMID- 17286901 TI - [Expression of predicted B cell epitope peptide in S2 subunit of SARS coronavirus spike protein in E.coli and identification of its mimic antigenicity]. AB - AIM: To study the expression of predicted B cell epitope peptide in S2 subunit of SARS coronavirus spike protein in E.coli and its mimic antigenicity to S2 protein. METHODS: B cell epitopes in S2 subunit of SARS coronavirus spike protein was predicted using DNAStar software. The cDNA sequence encoding the B cell epitope peptide was constructed artificially by PCR and then cloned into the downstream of chaperone 10 gene in vector pET28a(+) to construct pET28-chap10 S2epi plasmid. The fusion protein, chap10-S2epi, was expressed in E.coli BL21(DE3) and identified by SDS-PAGE and Western blot. The rabbit was immunized by purified Chap10-S2epi for the preparation of antiserum, which was used to identify the mimic antigenicity of Chap10-S2epi to S2 protein by ELISA. RESULTS: Chap10-S2epi fusion protein was successfully constructed and expressed in E.coli. The antiserum from the animal immunized by Chap10-S2epi recognized full length of SARS coronavirus S2 spike protein. CONCLUSION: The predicted B cell epitope peptide of SARS coronavirus S2 spike protein can induce the antigenicity of S2 protein, which provides some fundamental data for developing engineering vaccine against SARS coronavirus infection. PMID- 17286903 TI - [Enhancement of glioma cell apoptosis induced by anti-human DR5/DR4 monoclonal antibodies by sub-toxic dose of doxorubicin in human]. AB - AIM: To study the cytotoxic effects of doxorubicin on apoptosis in glioma cell lines U343, U138, U373 induced by anti-human DR4/DR5 monoclonal antibodies (FMU1.4/FMU1.5) and the underlying mechanism. METHODS: Expression of DR4/DR5 was quantitated by flow cytometry. Cytotoxicity exerted by FMU1.4/FMU1.5 on three cell lines was measured by MTT colorimetry and the induced apoptosis was determined by agarose gel electrophoresis. The expression of cytochrome C, FLIP and Ca2+ concentration were also measured. RESULTS: Following the treatment of doxorubicin DR4 and DR5 were highly expressed on the cell surface; The apoptosis of U138 and U373 induced by FMU1.4 and FMU1.5 was stronger. expression of cytochrome C and Ca2+ concentration were enhanced, whereas the expression of FLIP was downregulated. CONCLUSION: Subtoxic doxorubicin applied with antibodies caused higher cell death rate of glioma cells, which may be relevant to DR4/DR5, the release of cytochrome C and FLIP and Ca2+ concentration. PMID- 17286904 TI - [Serum IL-21 level in patients with primary Sjogren's syndrome and clinical significance of IL-21]. AB - AIM: To investigate the relation between the change of serum IL-21 level and other laboratory indexes by detecting serum IL-21 level from patients with primary Sjogren's syndrome (pSS) and explore the role of IL-21 in pSS. METHODS: The level of serum IL-21 from 40 pSS patients diagnosed according to 2002 revised international classification criteria for pSS and 30 healthy persons were detected by enzyme-linked immunosorbent assay(ELISA) respectively. Meanwhile, FT3, FT4, TSH, TgAb, TPOAb were detected by Immunochemiluminescent technique. Double diffusion method, Westergren and automatic gel method detected ant-SSA and ant-SSB antibody, ESR and serum protein electrophoresis respectively. The relationship between serum IL-21 level and other clinical symptom of the patients was analyzed. RESULTS: The level of serum IL-21 in patients with pSS (1051+/-335) ng/L was obviously higher than that in healthy control (466+/-90 ng/L), (P<0.05). The levels of serum IL-21 in the self-antibody positive group, parotid gland swelling pain group, rash group and incorporating hypothyroidism group were higher than those in their negative control groups, and there were significant differences(P<0.05). In addition, The level of serum IL-21 level in pSS patients showed positive correlation with gamma-globulin (r=0.719, P<0.05) and ESR level(r=0.745, P<0.05). CONCLUSION: The evident increase of serum IL-21 level in pSS patients has positive correlation with the levels of gamma-globulin and ESR, which suggests that IL-21 may play a critical role in the pathogenesis of pSS. PMID- 17286905 TI - [Effect of insulin-like growth factor I on the transdifferentiation and collagen synthesis of human renal tubular epithelial cells]. AB - AIM: To investigate the role of insulin-like growth factor I(IGF-I) in transdifferentiation and collagen synthesis of human renal tubular epithelial cell line HK2 in vitro. METHODS: Cultured HK2 cells were divided into two groups: (1) control group; (2) IGF-I-treated group(25, 50, 100, 200 microg/L, respectively). The cell morphological changes were traced with inverted microscope, and the expression of alpha-smooth muscle actin (alpha-SMA), collagen I alpha and collagen III alpha mRNA was detected by RT-PCR. Concentration of collagen I secreted into the culture supernatant was determined by ELISA. RESULTS: In HK2 cells, IGF-I stimulated the morphological oval-to-fusiform transdifferentiation of the cells, and upregulated alpha-SMA, collagen I alpha and collagen III alpha mRNA expression(P<0.05). Secreted collagen I level was also up-regulate by IGF-I in the concentration of 100 and 200 microg/L, respectively. CONCLUSION: IGF-I can promote the transdifferentiation of human renal tubular epithelial cells and stimulate the synthesis of collagen. PMID- 17286906 TI - [Immunogenicity of experimentally combined hepatitis A and hepatitis E vaccine at different dosage ratio]. AB - AIM: To evaluate the immunogenicity of experimentally combined hepatitis A and hepatitis E (cHA+E) vaccine and analyze the interactions between the two antigenic components in vaccine. METHODS: Nine different dosage ratio of the cHA+E vaccine, A500 + E200, A500 + E100, A500 + E50, A250 + E200, A250 + E100, A250 + E50, A125 + E200, A125 + E100 and A125 + E50 (U+mg)/L, was prepared from an inactivated hepatitis A (HA) vaccine and a hepatitis E (HE) vaccine. 120 mice were immunized with the cHA+E vaccine, HA vaccine and HE vaccine alone in different doses, respectively. Mice were bled before immunization and 2, 4, 6, 8, 10, 12 and 14 weeks post immunization. Specific antibodies against hepatitis A and E viruses were detected by ELISA and neutralization assay. RESULTS: After immunization with different dosages of cHA+E vaccine, all animals developed hepatitis A virus antibody (anti-HAV) and hepatitis E virus antibody (anti-HEV). Anti-HAV responses increased with the concentration of the HA vaccine component in the cHA+E vaccine. Anti-HAV neutralizing antibody titers reached 1:1 024 when mice were immunized with cHA+E vaccine prepared from higher dosage (500 U/mL) of the HA vaccine. The titers only reached 1:512 when lower dosages (250 and 125 U/mL) of HA vaccine were applied. However, different dosages (200, 100 and 50 mg/L) of the HE vaccine component in the cHA+E vaccine developed no effects on the production of anti-HAV neutralizing antibody. In addition, comparing with the single HE vaccine, the cHA+E vaccine induced higher level of anti-HEV response. The anti-HEV level increased with the concentration of HA vaccine component in the cHA+E vaccine. However, there was no obvious relationship between the anti HEV levels and the different dosages (200, 100 and 50 mg/L) of the HE vaccine component in the cHA+E vaccine. Immune sera elicited by the cHA+E vaccine neutralized HEV infectivity when detected by an in vitro RT-nPCR-based HEV neutralization assay. CONCLUSION: In cHA+E vaccine, the HA vaccine component can increase the immunogenicity of the HE vaccine component, and the HE vaccine component plays no adverse effects on the immunogenicity of the HA vaccine component. PMID- 17286907 TI - [Expression and preliminary study of HCV F protein gene]. AB - AIM: To express HCV F protein gene fragment in E.coli and detect if there is its antibody in HCV patients. METHODS: RNA of the virus identified as genetype 1b was choosed as template, the F protein gene was amplified by RT-PCR. This gene fragment was inserted into plasmid vector pGEM simple T. F gene was digested by EcoR I and BamH I from pGEM and cloned into plasmid vector pGEX-4T-2. The ligation mixture was transformed into E.coli. TG1 and F fragment expression was induced by IPTG. The expressed protein was purified from lysates with Glutathione Sepharose 4B. The purified protein was used to identify whether there was anti-F antibody in the patients which HCV RNA was positive by ELISA. RESULTS: After IPTG induction, a positive band about 43 kD was detected. 82 of 120 HCV RNA positive's sera had anti-F antibody by ELISA. CONCLUSION: It is possible to efficiently express the HCV F protein in E.coli. The positive rate of anti-F antibody in HCV RNA positive patients was 68%. PMID- 17286909 TI - [Synthesis of dominant epitopes on N-terminal part of BPI and preparation of corresponding antisera]. AB - AIM: To synthesize B cell dominant epitopes on N-terminal part of bactericidal/permeability increasing protein (BPI) and prepare the corresponding antisera. METHODS: The antigenicity, hydrophilicity, flexibility, surface probability and secondary structure of N-terminal amino acids 1-199 on BPI were predicted by bioinformatics applications. Two antigen peptides TA/IK were designed and synthesized on the basis of the above analysis. Then the TA/IK were respectively conjugated to keyhole limpet hemocyanin (KLH) and injected into rabbits to prepare corresponding antisera. Indirect ELISA was performed to analyze the antigenicity of TA/IK and to test the titer of the antisera. And Western blot was used to identify the specificity of the antisera. RESULTS: (1) Two B cell epitope-based peptides TA/IK were successfully synthesized; (2) the peptides could bind to commercial polyclonal antibody, anti-BPI(55); (3) titers of the antisera against TA/IK were up to 1:51,200, 1:25,600, respectively; (4) Western blot analysis revealed that these antisera could specifically react with the standard sample of BPI(55). CONCLUSION: The two synthetic antigen peptides TA/IK are indeed dominant epitopes of BPI N-terminal part, and the corresponding antisera are competent for detecting and identifying the N-terminal fragments of BPI. PMID- 17286908 TI - [Effects of aldosterone on synthesis of fibronectin and expression of transforming growth factor-beta1 mRNA in cultured rat mesangial cells]. AB - AIM: To evaluate the effect of aldosterone (ALD) and spironolactone (SPI, one of the aldosterone receptor antagonists) on synthesis and secretion of fibronectin (FN) and expression of transforming growth factor-beta1 (TGF-beta1) mRNA in cultured rat mesangial cells. METHODS: (1) Mesangial cells were treated with medium containing different concentrations of ALD (10(-11), 10(-9), 10(-7) mol/L) and/or 10(-7) mol/L SPI for 48 h, while control cells were treated with vehicle only. The levels of FN in the supernatants were measured by ELISA method. The expressions of FN mRNA and TGF-beta1 mRNA were detected by semi-quantitative RT PCR. (2) Mesangial cells were treated with 10(-9) mol/L ALD for 24, 48, 72 h. The levels of FN in the supernatants were measured by ELISA method. The expressions of FN mRNA and TGF-beta1 mRNA were detected by semi-quantitative RT-PCR. RESULTS: ELISA method showed that the level of FN in the supernatant of cultured rat mesangial cells stimulated with ALD increased significantly in a dose- and time dependent manner. Also the expressions of FN mRNA and TGF-beta1 mRNA were increased significantly by ALD in a dose- and time-dependent manner by semi quantitative RT-PCR. SPI inhibited the stimulating effect of ALD on synthesis of FN and expressions of FN mRNA and TGF-beta1 mRNA in cultured rat mesangial cells. CONCLUSION: ALD up-regulates the protein synthesis and mRNA expression of FN, and up-regulates the mRNA expression of TGF-beta1 in cultured rat mesangial cells. SPI inhibits the effect of ALD, and thus implication in the treatment of Glomerulosclerosis. PMID- 17286910 TI - [Preparation and characterization of monoclonal antibody against human carboxylesterases-II]. AB - AIM: To prepare monoclonal antibody(mAb) against human carboxylesterases-II (hCE II) and characterize its properties. METHODS: BALB/c mice were immunized with human liver microsome protein which contained hCE-II. The mAb was prepared by hybridoma technique and purified by protein-G affinity chromatography. The titer and specificity of mAb was detected by ELISA and Western blot respectively. Tissue localization of antigen was detected by immunohistochemical staining. Antigen was appraised by peptide mass fingerprint (PMF) matched with Mascot human protein database. PMF was obtained by immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: One clone of hybridoma secreting specific mAb against hCE-II was obtained. The Ig subclass of the mAb was IgG1(kappa). The titer of the mAb was 1 x 10(-7). Western blot analysis showed one clear belt in the Mr of 62,000. Immunohistochemistry demonstrated that the mAb had special combination with the liver cytoplasm protein, but not with the vascular smooth muscle cell protein. Immunoprecipitation showed one clear band in the Mr of 62,000, which was in conformity with the Mr of hCE-II and the antigen was confirmed to be hCE-II after being analyzed with mass spectrometry. CONCLUSION: The mAb against hCE-II with high titer and specificity has been obtained, which lays the foundation for investigation of hCE-II function and diagnosis and therapy of liver cancer. PMID- 17286911 TI - [Construction and screening of the specific Fab phage antibody library against Raji cell strain]. AB - AIM: To construct and screen the specific Fab phage antibody library against human Raji cell strain in B-lymphoma. METHODS: BALB/c mice were immunized with Raji cells, and the antibody light chain kappa genes and heavy chain genes Fd from the spleen cells were amplified by RT-PCR. After restrictive digestion with Sac I/Xba I and Xho I/Spe I, the light chain kappa genes and heavy chain genes Fd were inserted into the phagemid vector pComb3H-SS successively and then electroporated into E.coli XL1-Blue. The specific Fab phage antibody library against Raji cell strain in human B-lymphoma was constructed by infection of helper phage VCSM13. The specific antibodies against Raji cells were obtained after selected with Raji cells. The binding activity with antigens was identified by ELISA and the positive clones were sequenced. RESULTS: The Fab phage antibody library with 2.18 x 10(7) volume was constructed and eight positive clones which specifically recognized Raji cell strain were isolated. Sequence analysis of the two positive clones showed that the variable heavy domains (VH) and variable light domains (VL) were highly homologous with the registered murine Ig heavy chain V region sequences and kappa light chain sequences, respectively. CONCLUSION: Fab phage antibody library was successfully constructed and specific antibodies against membrane antigens in Raji cells were obtained, which will provide an experimental foundation for the further investigation of B-lymphoma immunotherapy. PMID- 17286912 TI - [Study on the cytotoxicity of spleen lymphocytes and immune mechanisms in mice immunized by Mycobacterium tuberculosis H37Ra]. AB - AIM: To explore the specific cytotoxicity of spleen lymphocytes and the immune mechanisms in mice immunized by Mycobacterium tuberculosis(MTB) H37Ra. METHODS: At the various interval (30 days, 60 days) after the mice were immunized by MTB H37Ra, BCG and PBS, the spleen lymphocytes of the immunized mice were used as the effector cells while the Sp2/0 cells expressing the secreted protein Ag85B were used as the target cells, and the cytotoxicity of spleen lymphocytes in the immunized mice was measured by MTT assay. Spleen lymphocytes were collected at 60 days after immunization and stimulated with PPD, and the expression of perforin, granzyme B on mRNA level was detected by RT-PCR. RESULTS: The cytotoxicity of spleen lymphocytes in the group immunized by MTB H37Ra was significantly higher than that of PBS control group (P<0.05), and slightly higher than that of BCG group. The mRNA expression of perforin, granzyme B in H37Ra group and BCG group was significantly higher than that in PBS control group (P<0.05); the expression of perforin mRNA in H37Ra group was significantly higher than that in BCG group (P<0.05), but there was no obvious difference with regard to the expression of granzyme B mRNA between H37Ra group and BCG group. CONCLUSION: The cytotoxicity of spleen lymphocytes is enhanced after mice were immunized by MTB H37Ra, which may be related to the expression of perforin and granzyme B. PMID- 17286913 TI - [Cytokine expression of CD4+ and CD8+ T cells induced by different stimuli under different culture conditions]. AB - AIM: To investigate the effect of different stimuli and different culture conditions on the cytokine expression of CD4+ and CD8+ T cells. METHODS: PBMCs were isolated from normal human peripheral blood and cultured with three kinds of stimuli (PHA, anti-CD3 and anti-CD28 mAbs, PMA and ionomycin) under four different culture conditions (room temperature, 37 degrees C water bath, 37 degrees C incubator, 37 degrees C and 50 mL/L CO2 incubator) for 4.5 ~ 5 h and intracellular cytokines (IL-2, IFN-gamma and TNF-alpha) in T cells were assessed by flow cytometry (FCM). RESULTS: Cytokine expression of CD4+ and CD8+ T cells varied when treated with different stimuli under different conditions. PMA had the strongest stimulative effect on cytokine expression of PBMC, while the effect of anti-CD3 mAb was weaker, and that of PHA was the weakest. Different culture conditions did not greatly change the cytokine expression profile of T cells (P>0.05) except that there were very few cytokine producing cells when PBMCs were cultured at room temperature. CONCLUSION: Anti-CD3 and anti-CD28 mAbs, PMA and ionomycin are recommended for the stimulation of PBMCs and detection of intracellular cytokine using FCM. Culture temperature but not the concentration of CO2 is the most important factor during the short term T cell stimulation. PMID- 17286914 TI - [Biological characteristics and effect of TNF-alpha binding peptide and TNFR blocking peptide in vitro]. AB - AIM: To investigate the biological characteristics and effect of TNF-alpha binding peptide (TBP) and TNFR blocking peptide (TRBP) in vitro. METHODS: The binding specificity of TBP or TRBP was tested by competition experiment using GFP TNF fusion protein and detected by FCM and fluorescent microscope. The interaction between TBP and TRBP was determined by non-denatured PAGE and the inhibitory effect of TBP and TRBP on TNF-alpha cytotoxicity against U937 was carried out by MTT colorimetry. The effects of TBP and TRBP on the functions of human monocytes activated by TNF-alpha and IFN-gamma in vitro were detected by nitrotetrazolium blue chloride (NBT) reduction assay for evaluating respiratory burst and by RT-PCR for evaluating IL-1beta and IL-8 mRNA transcription. RESULTS: It was showed that TBP and TRBP was able to block the GFP-TNF binding to the TNFR on the surface of cells and no binding interaction took place between TBP and TRBP. Both TBP and TRBP were able to inhibit the TNF-alpha cytotoxicity against U937 and this inhibitory effect was dose-dependent and the combination of TBP and TRBP (pep.38+X4) was able to inhibit the TNF-alpha cytotoxicity more efficiently than the individual peptide at all tested concentrations. The combination of TBP and TRBP was able to obviously inhibit both respiratory burst of monocytes induced by TNF-alpha and IFN-gamma and transcription level of IL-1beta and IL-8 mRNA induced by TNF-alpha. CONCLUSION: TBP or TRBP can bind with their ligands specifically and don't interact with each other. They can also block the biological activity of the TNF-alpha in vitro, and the combination of TBP and TRBP is able to inhibit the biological activity of the TNF-alpha more efficiently. This research will provide an experimental basis for the clinical treatment of the inflammatory disease. PMID- 17286915 TI - [Home care: walking towards excellence]. PMID- 17286916 TI - [Complementary medicines in oncology]. PMID- 17286917 TI - [Social profiles, diet, and prediction of eating disorders in urban andalusian adolescents]. AB - OBJECTIVE: To know the social profile of Andalusian urban adolescents and analyse the similarities and differences they have with those at risk of presenting with eating disorders. DESIGN: Cross-sectional community study. Stratified cluster sampling. SETTING: Public and private education institutions in Andalusian cities with more than 100 000 inhabitants (Sevilla, Malaga, Granada, Cordoba, Cadiz, Huelva, Almeria, Jaen, Algeciras, and Jerez). PARTICIPANTS: Pupils from 12 to 16 years, attending an academic course in the year 2002-2003 (N=1667). MAIN MEASUREMENTS: To compare the results of the sample with adolescents who are at risk of presenting with eating disorders (those who scored more than 20 in the 26 item Eating Attitudes Test [EAT-26]) we used the chi2 test for the nominal variables and the Spearman rho for the interval variables, with a significance level of P=.05. RESULTS: There were no differences between either group as regards family structure, friend relationships, academic performance, and sporting activities. The differences centred on disciplinary practices, the number of friends diagnosed with an eating behavioural disorder, the objectives for practicing sports, and the type of diet that they followed. The subjects who scored highest on the EAT-26 were those who had a higher body mass index and a lower social status. CONCLUSIONS: It appears that diet changes are a response to certain social conditions. It would be speculative to include subjects who obtain high EAT-26 scores in the population at risk of anorexia. PMID- 17286918 TI - [Care of adolescents and detection of disorders in eating behaviour: we have to take a step forward]. PMID- 17286919 TI - [A systematic review of therapy coordination between primary and specialist care]. AB - OBJECTIVES: To evaluate existing information on questions of therapy coordination between primary and hospital care and to identify activities with positive results that could be adapted at the local level. DESIGN: Systematic review. DATA SOURCES: MEDLINE, SIETES, and Cochrane systematic review databases were searched for articles published between January 1990 and August 2005. SELECTION OF STUDIES: Those conducted in countries with a National Health Service. Thirty-six studies were included: a) observational studies on drug prescription for patients moving between primary and specialist care (18 studies); b) studies of the views of health professionals: review and consensus articles and editorials (7 articles); qualitative studies (4 articles); c) intervention studies (7 studies). Four-hundred and thirty-one studies were excluded. RESULTS: The most common problems were: lack of information for patient follow-up, disagreement in drug selection, increases in costs due to hospital stays and difficulties in assuming clinical responsibilities. The solution put forward was that a unified policy of common medicines and budgets is essential. Little information was available on the studies that posed or evaluated interventions to improve therapy coordination. Conditions with the most information available were heart failure, diabetes mellitus, asthma, high blood pressure, and anticoagulant treatment. CONCLUSIONS: The creation of pharmacotherapy committees, involving professionals belonging to both primary and specialist care, was proposed. These committees would adapt for local use protocols and clinical practice guidelines, in line with the prescription quality standards of primary care. PMID- 17286920 TI - [Attitudes of family doctors to patients' rights]. AB - OBJECTIVES: To examine the attitudes of family doctors to patients' rights and to ascertain the social and professional variables that influence these views. DESIGN: Descriptive, cross-sectional study based on a questionnaire. SETTING: Primary care, Murcia, Spain. PARTICIPANTS: Two-hundred and twenty-seven family physicians, who filled in a postal questionnaire. INTERVENTIONS: The questionnaire included social and professional variables, evaluation of job satisfaction (by Likert scale 1-5), evaluation of patients' rights (Likert scale 1-5). MAIN MEASUREMENTS AND RESULTS: The most valued right in the overall view of the doctors questioned was the right to suitable health care within a humane framework (4.86; 95% CI, 4.81-4.91), while the least valued right was the access to medical records (3.91; 95% CI, 3.76-4.05). Mean job satisfaction was 2.79 (95% CI, 2.71-2.87). We found: statistically significant differences in the assessment of patients' rights, which depended on various social and professional factors; direct associations between doctors' satisfaction and their views on patients' rights; and a significant correlation between overall evaluation of rights and total satisfaction (P=.039). CONCLUSIONS: Overall, family doctors attach a lot of importance to patients' rights. However, social and professional characteristics seem to have some influence on their attitudes: older doctors, those working in an urban context, those with few patients on their lists, in teaching centres, and those feeling the greatest professional satisfaction tend to attach greater importance to patients' rights. PMID- 17286921 TI - [Treatment of chronic osteomuscular pain]. AB - OBJECTIVE: To describe the prevalence of use of the 3 analgesic steps of the WHO in patients with chronic osteomuscular pain at 2 primary care centres, by means of personal interviews during the second semester of 2003 and first of 2004. DESIGN: Cross-sectional, observational, descriptive study. SETTING: Health centres of Puerto de Sagunto (Valencia) and Alto Palancia (Castellon), Spain. PARTICIPANTS: Three-hundred and twenty users of the above centres with chronic osteomuscular pain. METHOD: Systematic random sampling of the patients. Data collected from clinical histories and personal interviews. RESULTS: Thirty-eight percent (38.7%) of the patients did not take medication to control pain or did so at insufficient doses; 54.7% used drugs of the first step of the WHO; and 6.6%, of the second. There were no patients in treatment with strong opioids. Significant differences at the time of prescribing the different analgesic treatments existed, depending on sex, educational background and patients' job. The characteristics of chronic pain (aetiology and duration of symptoms) also affected the therapy decision. There was a tendency to prescribe more analgesic as pain intensified. CONCLUSIONS: There is a high percentage of the population without any treatment for chronic osteomuscular pain. Opioid analgesics are under used to treat pain. PMID- 17286923 TI - [Framework of competences of family doctors: clinics or people?]. PMID- 17286922 TI - [Proposal for presbycusis screening in a primary care clinic]. AB - OBJECTIVES: Presbycusis is one of the causes of deafness that has increased most in our society. To show the levels of presbycusis in people over 60 who attend our health centre for other reasons and to assess the utility of certain tests employed in primary care to detect hearing problems. PATIENTS AND METHOD: One hundred and ten people. EXCLUSION CRITERIA: prior specialist diagnosis, lack of consent or impossibility of running the tests. Assessment of auditory invalidity: otoscopy, Weber, Rinne, whispered voice, auditory disability test. Audiological validation by audiometry assessed by ORL. Results analysed with SPSS statistical packet. RESULTS: Mean age 714 (6.1). Otoscopy was normal in 81.8%. Weber's test had no significant relationship with the otoscopy, but did with the Rinne. Presbycusis was seen in 68.2% of the audiometries. Everyone (100%) who had worked in a noisy environment had audiometric deficit. CONCLUSIONS: There were high figures (87%) for hypoacusis in our population of elderly people. In 68.2%, this was due to presbycusis. The sensitivity and negative predictive value (Vp-) of most of the tests used in primary care to detect auditory disorders are low. PMID- 17286924 TI - [Palliative sedation and euthanasia]. PMID- 17286925 TI - [Primary care centres as generators of information on organ donation]. PMID- 17286926 TI - [Chronic auricular fibrillation: can it be controlled in primary care?]. PMID- 17286927 TI - [Behaviour of the diagnosis 127-related group on cardiac failure in Andalusia during 2002]. PMID- 17286928 TI - [Genetics and metabolic syndrome: a further opportunity for conducting integrated health interventions]. PMID- 17286942 TI - [After 25 years, new challenges]. PMID- 17286943 TI - [Treatment of Graves-Basedow's disease with 131I. Assessment of a "modulated fixed activity" protocol]. AB - PURPOSE: The purpose of this study was to retrospectively evaluate the hypothyroidism rate, persistence of hyperthyroidism and the complications after the administration of 131I in 3 cohorts defined according to the activity of 131I administered. METHODS: We consecutively treated 659 patients diagnosed with Graves-Basedow disease (GBD) with 131I. The activity was determined on the basis of a protocol that we called "modulated fixed activity". A total of 45 patients (Group 1) who had previously undergone surgery were given small 131I activities of between 111-185 MBq (3-5 mCi), 247 patients (Group 2) with normal or almost normal-sized thyroids were given activities of between 222-333 MBq (6-9 mCi) and the 367 patients with diffuse goiters (Group 3) activities of between 370-555 MBq (10-15 mCi). RESULTS: A total of 69.2 % of the patients presented hypothyroidism at the end of the follow-up period. By groups, the percentages of hypothyroidism at the end of the follow-up period were 69 %, 68.8 % and 69.6 % respectively. The average time for the patients to present hypothyroidism was 2.7 years with a maximum de 12.3 years and a minimum of 2 months. No severe precocious complications after the administration of 131I were noted. CONCLUSION: The choice of the modulated fixed doses of 131I for treatment of the GBD is a simple method and permit treatment in only one day. PMID- 17286944 TI - [Assessment of cortical brain blood flood by brain perfusion spect in patients with a diagnosis of eating behavior disorders]. AB - OBJECTIVE: To evaluate cortical brain blood flow by 99mTc-HMPAO SPECT in patients with Eating Disorders (ED): restrictive anorexia (RA) and purgative bulimia (PB). MATERIAL AND METHOD: The study included 7 women with diagnostic criteria of RA and 12 with PB. The control group was made up of 12 healthy women. All subjects underwent brain 99mTc-HMPAO SPECT. The SPECT studies were quantified, yielding semiquantitative indexes relating to cerebellar activity in different regions. Body dissatisfaction was assessed by means of the BSQ (Body Shape Questionnaire). The results were analyzed with the ANOVA variance and had a statistical significance of p < 0.05. RESULTS: Mean BSQ scores were 98.28 (range 71-159) in the RA group, 145.05 (range 73-191) in the PB group, and 57.4 (range 37-88) in the control group. All patients in the sample (i.e., both RA and PB) showed global cerebral hypoperfusion versus the controls, although the difference only reached statistical significance in the RA group in the left parietal lobe (p = 0.02) and in the right (p = 0.004) and left temporal lobes (p = 0.015). In the PB group, the significantly hypoperfused regions were the right (p < 0.001) and left (p = 0.008) superior frontal lobe, the right inferior frontal lobe (p = 0.042), the right (p = 0.042) and left (p = 0.002) parietal lobes, and the right temporal lobe (p = 0.002). CONCLUSION: The results obtained showed that patients with ED had cerebral hypoperfusion compared with healthy subjects. This pattern is common in parietotemporal regions for both PB and AR although with temporal and parietal predominance in RA and PB, respectively. In addition, patients with PB had frontal region involvement. PMID- 17286945 TI - [Meta-analysis of the diagnostic performance of 18F-FDG PET in renal cell carcinoma]. AB - AIM: Renal cell carcinoma is the most frequent solid kidney tumor. At present, PET is not the imaging test of choice, the helical CT being the best method to assess these patients. The aim of the study was to perform a meta-analysis of the literature to evaluate the performance and accuracy of 18F-FDG PET in the detection of primary disease, recurrence and metastasis of renal cell carcinoma. MATERIALS AND METHODS: A systematic search was done of the available literature in primary and secondary databases published until October 2004 indexed in MEDLINE and CANCERLIT. Exclusion/inclusion criteria were applied. Their quality was evaluated using the Flynn criteria and joint estimators of sensitivity (S), specificity (Sp), likelihood ratios (LR), diagnostic odds ratio (DOR) and summary ROC (SROC) curve were obtained. The presence of the threshold effect was evaluated and the summary ROC (SROC) curve was calculated. RESULTS: Seven out of 46 studies fulfilled the inclusion criteria and were analyzed. Three studies evaluated the use of 18F-FDG PET in the differential diagnosis of renal masses. Two studies analyzed restaging and two analyzed the role of 18F-FDG PET in the detection of metastatic disease. All the selected studies were classified according to Flynn's criteria. We found the highest S in restaging with S 0.87 (95 % CI, 0.75-0.95) and in metastases detection with S 0.72 (95 % CI, 0.56-0.85) as well as the high Sp in differential diagnosis of renal masses. CONCLUSIONS: The results of this meta-analysis suggest that 18F-FDG PET can be useful in restaging and detection of metastatic disease, based on its acceptable S and Sp. However, the performance of 18F-FDG PET in the detection of primary disease is limited, but this may improve with the new PET/CT systems. PMID- 17286946 TI - [Evaluation of efficacy and clinical impact of positron emission tomography with 18F fluoro-deoxyglucose in patients with suspicion of recurrent head and neck cancer or distant metastases]. AB - AIMS: To evaluate the efficacy and clinical impact of Positron Emission Tomography with FDG (FDG-PET) in patients with suspected recurrent head and neck cancer or distant metastases. MATERIALS AND METHODS: Sixty patients (12 women and 48 men) with suspicion of recurrent head and neck cancer and ambiguous conventional imaging modalities. In all patients a whole body scan was performed with FDG-PET in fasting patients following i.v. administration of 370-444 MBq FDG. The results were confirmed by histology and clinical evolution (follow-up period > 12 months) and imaging test. RESULTS: Prevalence of recurrence was 66.6 %. FDG-PET was positive in 40/60 patients, with confirmation in 39 cases, and 18 were true negative (TN). We have found 2 false positive and 1 false negative. Overall sensitivity, specificity, PPV, NPV and accuracy were 97.5 %, 90 %, 95.12 %, 94.7 % and 95 %, respectively. FDG-PET changed the modality of treatment in 34 patients (clinical impact 56.6 %) CONCLUSIONS: FDG-PET has high clinical impact in patients with suspicion of recurrent head and neck cancer, and should be incorporated in the diagnostic protocols before making a therapy decision. PMID- 17286947 TI - Follicular dendritic sarcoma within a focus of Castleman's disease. Serial FDG PET/CT in the follow up of recurrence with histopathologic confirmation. AB - We report the case of a 30 year-old man with previous history of melanoma and new diagnoses of localized abdominal Castleman's disease with a focus of follicular dendritic sarcoma within the Castleman's tumor. He presented soon after with a single enlarged abdominal lymph node characterized and followed-up by FDG PET/CT as a low grade malignancy consistent with Castleman's recurrence. However, other imaging techniques raised the possibility of sarcoma/ melanoma recurrence. Final surgical resection allowed histological confirmation of the FDG PET/CT findings. To our knowledge, this is one of the few cases in the literature of Castleman's disease and follicular dendritic sarcoma association in the same focus. This is the first paper to our knowledge to use FDG PET/CT as the follow-up imaging tool for serial characterization of recurrence of Castleman's disease and follicular dendritic sarcoma. FDG PET/CT may be useful in the differentiation between Castleman's disease and malignancies associated with this disease. PMID- 17286948 TI - A possible cause of misinterpretation on radionuclide imaging: Chilaiditi's syndrome. AB - The authors of this work present two patients, diagnosed with lymphoma and prostate cancer, referred to nuclear medicine department for a gallium-67 scan and a bone scan, respectively. The abnormal accumulation of the radioactivity gave rise suspicion for possible other pathologies. Successive computed tomographic imaging revealed that the patients had had Chilaiditi's syndrome. The authors present these cases to draw attention for the possibility of misinterpretation of the scans due to distribution of radioactivity in this syndrome. PMID- 17286949 TI - [Foreign body granulomatous inflammation in PET/CT scan study with FDG in a patient with tumor recurrence of colorectoral carcinoma]. PMID- 17286950 TI - [Atypical uptake of gallbladder as cause of False-positive iodine-131 in post surgical removal scanning of thyroid remains]. PMID- 17286951 TI - [Nomenclator of the Nuclear Medicine procedures]. PMID- 17286952 TI - Histone H4 acetylation dynamics determined by stable isotope labeling with amino acids in cell culture and mass spectrometry. AB - This paper describes an integrated approach that couples stable isotope labeling with amino acids in cell culture to acetic acid-urea polyacrylamide gel electrophoresis (AU-PAGE) and matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOF MS) for the quantitation and dynamics of histone H4 acetylation. The 697 acute lymphoblastic cell lines were grown in regular medium and in medium in which lysine was substituted with deuterium labeled lysine. Histone deacetylase (HDAC) activity was inhibited by addition of the HDAC inhibitor depsipeptide to the culture medium for different exposure times. Histones were extracted from cells pooled from unlabeled, untreated cells and from labeled, treated cells, followed by AU-PAGE separation. Gel bands corresponding to different acetylation states of H4 were excised, in-gel digested with trypsin, and analyzed by MALDI-TOF MS. Detailed information was obtained for both the change of histone H4 acetylation specific to the N terminus and the global transformation of H4 from one acetylation state to another following treatment with the HDAC inhibitor depsipeptide. The kinetics of H4 acetylation was also assessed. This study provides a quantitative basis for developing potential therapies by using epigenetic regulation and the developed methodology can be applied to quantitation of change for other histone modifications induced by external stimuli. PMID- 17286953 TI - Determination of platinum in human subcellular microsamples by inductively coupled plasma mass spectrometry. AB - A fast and robust method for the determination of platinum in human subcellular microsamples by inductively coupled plasma mass spectrometry was developed, characterized, and validated. Samples of isolated DNA and exosome fractions from human ovarian (2008) and melanoma (T289) cancer cell lines were used. To keep the sample consumption to approximately 10 microl and obtain a high robustness of the system, a flow injection sample introduction system with a 4.6-microl sample loop was used in combination with a conventional pneumatic nebulizer and a spray chamber. The system was optimized with respect to signal/noise ratio using a multivariate experimental design. The system proved to be well suited for routine analysis of large sample series, and several hundreds of samples could be analyzed without maintenance or downtime. The detection limit of the method was 0.12 pg (26 pg/g) platinum. To avoid systematic errors from nonspectral interferences, it was necessary to use reagent matched calibration standards or isotope dilution analysis. An uncertainty budget was constructed to estimate the total expanded uncertainty of the method, giving a quantification limit of 2.3 pg (0.5 ng/g) platinum in DNA samples. The uncertainty was sufficiently low to study quantitative differences in the formation of Pt-DNA adducts after treatment with cisplatin using different exposure times and concentrations. PMID- 17286954 TI - Quantification of protein thiols and dithiols in the picomolar range using sodium borohydride and 4,4'-dithiodipyridine. AB - Experimental determination of the number of thiols in a protein requires methodology that combines high sensitivity and reproducibility with low intrinsic thiol oxidation disposition. In detection of disulfide bonds, it is also necessary to efficiently reduce disulfides and to quantify the liberated thiols. Ellman's reagent (5,5'-dithiobis-[2-nitrobenzoic acid], DTNB) is the most widely used reagent for quantification of protein thiols, whereas dithiothreitol (DTT) is commonly used for disulfide reduction. DTNB suffers from a relatively low sensitivity, whereas DTT reduction is inconvenient because the reagent must be removed before thiol quantification. Furthermore, both reagents require a reaction pH > 7.0 where oxidation by ambient molecular oxygen is significant. Here we describe a quick and highly sensitive assay for protein thiol and dithiol quantification using the reducing agent sodium borohydride and the thiol reagent 4,4'-dithiodipyridine (4-DPS). Because borohydride is efficiently destroyed by the addition of acid, the complete reduction and quantification can be performed conveniently in one tube without desalting steps. Furthermore, the use of reverse phase high-performance liquid chromatography for the thiol quantification by 4 DPS reduces the detection limit to the picomolar range (equivalent to 1 microg of a 50-kDa protein containing 1 thiol) while at the same time maintaining low pH throughout the procedure. PMID- 17286955 TI - Angiogenic activity of syndecan-binding laminin peptide AG73 (RKRLQVQLSIRT). AB - The AG73 peptide (RKRLQVQLSIRT, mouse laminin alpha 1 chain 2719-2730) promotes cell adhesion and tumor metastasis, and interacts with transmembrane syndecan proteoglycans. Here, we demonstrate AG73 peptide angiogenic activity using in vitro, ex vivo, and in vivo models. AG73 induced murine endothelial cell (SVEC4 10) tube formation on Cultrex Basement Membrane Extract (Cultrex BME) and stimulated sprouting of aortic rings. None of the homologous sequences from the laminin alpha2, alpha3, alpha4, or alpha5 chains was as active as AG73 in promoting sprouting formation. AG73 also mediated angiogenesis in the chick chorioallantonic membrane (CAM) assay. Using subcutaneously injected Cultrex BME supplemented with AG73, we observed a large angiogenic response. Furthermore, AG73-conjugated to a chitosan membrane promoted a strong angiogenic response in the CAM assay. These results indicate that the AG73 peptide is a potent syndecan binding angiogenesis stimulator and may be useful for therapeutic application to treat ischemic injuries. PMID- 17286956 TI - Involvement of over-expressed BMP4 in pentylenetetrazol kindling-induced cell proliferation in the dentate gyrus of adult rats. AB - The dentate gyrus (DG) of the hippocampus is one of a few regions in the adult mammalian brain characterized by ongoing neurogenesis. Proliferation of neural precursors in the granule cell layer of the DG has been identified in pentylenetetrazol (PTZ) kindling epilepsy model, however, little is known about the molecular mechanism. We previously reported that the expression pattern of bone morphogenetic proteins-4 (BMP4) mRNA in the hippocampus was developmentally regulated and mainly localized in the DG of the adult. To explore the role of BMP4 in epileptic activity, we detected BMP4 expression in the DG during PTZ kindling process and explore its correlation with cell proliferation combined with bromodeoxyuridine (BrdU) labeling technique. We found that dynamic changes in BMP4 level and BrdU labeled cells dependent on the kindling stage of PTZ induced seizure-prone state. The number of BMP4 mRNA-positive cells and BrdU labeled cells reached the top level 1 day after PTZ kindled, then declined to base level 2 months later. Furthermore, there was a significant correlation between increased BMP4 mRNA expression and increased number of BrdU labeled cells. After effectively blocked expression of BMP4 with antisense oligodeoxynucleotides(ASODN), the BrdU labeled cells in the dentate gyrus subgranular zone(DG-SGZ) and hilus were significantly decreased 16d after the first PTZ injection and 1, 3, 7, 14d after kindled respectively. These findings suggest that increased proliferation in the DG of the hippocampus resulted from kindling epilepsy elicited by PTZ maybe be modulated by BMP4 over-expression. PMID- 17286957 TI - Potential role of WISP3 (CCN6) in regulating the accumulation of reactive oxygen species. AB - Several mutations and atypical splice variants of WISP3 (CCN6) have been linked to connective tissue disorders and different forms of malignancies. Functional studies have suggested that WISP3 contributes to tissue maintenance/homeostasis. The precise molecular mechanism of WISP3 function in different cell types, however, remains unresolved. The present study was conducted to investigate the potential impact of WISP3 on the accumulation of reactive oxygen species (ROS) and oxidative stress, which are central to cell/tissue maintenance. Our experimental results suggest that WISP3 regulates the accumulation of cellular ROS, and mutations in WISP3 or loss of expression of WISP3 compromise this function. PMID- 17286958 TI - Salt stress enhances proline utilization in the apical region of barley roots. AB - Accumulation of an osmoprotectant, proline, is enhanced in response to salinity in plants. Here, by immunohistochemical analysis, we demonstrated that proline transporter (HvProT) was highly expressed in the apical region of barley roots under salt stress. Free proline was accumulated more in the basal region than in the apical region of barley roots under salt stress, although expression level of HvProT was higher in the apical region. On the other hand, salt stress increased proline and hydroxyproline contents in the cell wall fraction of the root apical region, suggesting increment of proline utilization. Expression of the genes encoding cell wall proteins (proline rich protein and extensin) and cellulose synthase was induced in barley roots by salt stress. These findings indicated that free proline transported by HvProT presumably behaved as a component of cell wall synthesis in the apical region of barley roots under salt stress. PMID- 17286960 TI - Pillar cell and erythrocyte localization of fugu ET(A) receptor and its implication. AB - Endothelin, a vasoconstrictor peptide, plays important roles not only in the mammalian circulatory system but also in non-mammalian systems, such as the gill lamellar vascular network with complex structural characteristics. Here, we show that (i) the contraction of pillar cells that delimit the lamellar vasculature is controlled by endothelin through the type A endothelin receptor (ET(A)) linked to the intracellular calcium signaling system and (ii) ET(A) receptor is also highly expressed on fugu erythrocytes, a hitherto unexpected finding. Database mining revealed the presence of five endothelin receptor (ETR) sequences in the fugu genome. By Northern blotting, cDNA cloning, and fura-2 monitoring, the branchial ETR subtype was shown to be ET(A) able to induce a Ca(2+) transit. Immunohistochemistry revealed its pillar cell and erythrocyte localization. These results suggest an endothelin/ET(A)-mediated coordinated regulation of the pillar cell shape and erythrocyte membrane flexibility. PMID- 17286959 TI - Expression of skeletal muscle Na(V)1.4 Na channel isoform in canine cardiac Purkinje myocytes. AB - BACKGROUND AND AIM: The action potential plateau of Purkinje fibers is particularly sensitive to tetrodotoxin (TTX) and this could be due to a TXX sensitive Na(+) current. The expression of TTX-sensitive neuronal Na(V)1.1 and Na(V)1.2 isoforms has been reported in canine Purkinje myocytes. Our aim was to investigate by means of biochemical and functional techniques whether the TTX sensitive skeletal Na(V)1.4 isoform is also expressed in canine cardiac Purkinje myocytes. METHODS AND RESULTS: Using Na(V)1.4 specific primers, a PCR product corresponding to Na(V)1.4 was amplified from canine Purkinje fibers RNA and confirmed by sequencing and megablast of the gene bank. Confocal indirect immunostaining using anti-Na(V)1.4 antibody demonstrates distinct sarcolemmal staining pattern compared to that of the cardiac isoform Na(V)1.5. Expression of Na(V)1.4 in tsA201 cells yielded a TTX-sensitive Na(+) current with an IC(50) of 10nM. CONCLUSIONS: These results demonstrate the expression of the TTX-sensitive Na(V)1.4 channel in canine cardiac Purkinje myocytes. This novel finding suggests a role of Na(V)1.4 channel in Purkinje myocytes and thus has important clinical implications for the mechanisms and management of ventricular arrhythmias originating in the Purkinje network. PMID- 17286961 TI - Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division. AB - BRCA2 is responsible for familial breast and ovarian cancer, and its gene product is linked to DNA repair and transcriptional regulation. The BRCA2 protein exists mainly in the nucleus. Here, we show that BRCA2 has a centrosomal localization signal (CLS), localizes also to centrosomes during S and early M phases, and may regulate duplication and separation of the centrosomes. Green fluorescent protein (GFP) fused to the CLS peptides from BRCA2 (GFP-CLS) localizes to centrosomes and prevents endogenous BRCA2 from localizing to centrosomes. In addition, expression of GFP-CLS in cells leads to the abnormal duplication and positioning of centrosomes, resulting in the generation of multinuclear cells. These results thus implicate BRCA2 in the regulation of the centrosome cycle, and provide new insight into the aneuploid nature of many breast cancers. PMID- 17286962 TI - Efficient capture of cardiogenesis-associated genes expressed in ES cells. AB - Cardiogenesis can be induced in vitro in ES cells, though it is difficult to distinguish cardiac-specific genes, since embryoid bodies simultaneously differentiate into multiple lineages. In the present study, transient serum removal during culture greatly enhanced cardiogenesis, and reduced generation of endothelial and hematopoietic cells. Using DNA microarray analysis of 24 differentiated sample cultures including cardiogenesis-enhanced cells, we successfully selected genes up-regulated in embryoid bodies that had undergone cardiogenic differentiation. Besides contractile protein genes, cardiac transcriptional regulatory genes, such as Nkx2-5, Gata4/5, Mef2c, and Myocd, were primary constituents of the first 100 genes chosen as cardiogenesis-associated genes. Further, whole mount in situ hybridization analysis of 13 genes containing non-characterized ones confirmed that most of them were specifically expressed in the heart region of mouse embryos from E9.5-10.5. Based on our results, we consider that the present profiling method may be useful to identify novel genes important for cardiac development. PMID- 17286963 TI - P2X(7) receptor activation causes phosphatidylserine exposure in human erythrocytes. AB - Activation of cation channels causes erythrocyte phosphatidylserine (PS) exposure and cell shrinkage. Human erythrocytes express the P2X(7) receptor, an ATP-gated cation channel. The two most potent P2X(7) agonists, BzATP and ATP, stimulated PS exposure in human erythrocytes. Other nucleotides also induced erythrocyte PS exposure with an order of agonist potency of BzATP>ATP>2MeSATP>ATPgammaS; however neither ADP nor UTP had an effect. ATP induced PS exposure in erythrocytes in a dose-dependent fashion with an EC(50) of approximately 75 microM. BzATP- and ATP induced erythrocyte PS exposure was impaired by oxidised ATP, as well as in erythrocytes from subjects who had inherited loss-of-function polymorphisms in the P2X(7) receptor. ATP-induced PS exposure in erythrocytes was not significantly altered in the presence of EGTA excluding a role for extracellular Ca(2+). These results show that P2X(7) activation by extracellular ATP can induce PS exposure in erythrocytes. PMID- 17286964 TI - Novel substrates of Mycobacterium tuberculosis PknH Ser/Thr kinase. AB - PknH Ser/Thr protein kinase of Mycobacterium tuberculosis controls the expression of a variety of cell wall related enzymes and regulates the in vivo growth in mice. Therefore, we predicted that the PknH kinase could phosphorylate several substrates controlling different metabolic and physiological pathways. Using a bioinformatic approach, we identified 40 potential substrates. Two substrates were shown to be phosphorylated by recombinant PknH kinase in vitro. Point mutation studies verified that substrates are phosphorylated at the in silico predicted sites. Kinetic studies revealed a similar relative-phosphorylation rate (V(max)) of PknH towards two new substrates and the only previously known substrate, EmbR. Unlike the EmbR protein, the Rv0681 and DacB1 proteins do not contain an FHA domain and are possible participants of new signaling pathways mediated by the PknH kinase in M. tuberculosis. PMID- 17286965 TI - Reversal of multidrug resistance by 4-chloro-N-(3-((E)-3-(4-hydroxy-3 methoxyphenyl)acryloyl)phenyl)benzamide through the reversible inhibition of P glycoprotein. AB - Overexpression of P-glycoprotein (P-gp) is one of the major obstacles to successful cancer chemotherapy. In this study, we examined the ability of 4 chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide (C-4) to reverse multidrug resistance (MDR) in P-gp expressing KBV20C cells. Treatment of KBV20C cells with C-4 led to a dramatic increase in paclitaxel- or vincristine induced cytotoxicity without any cytotoxicity by itself. In parallel, C-4 treatment caused an increase in apoptotic cell death by paclitaxel or vincristine. Furthermore, C-4 treatment significantly increases in intracellular accumulation of fluorescent P-gp substrate rhodamine 123, indicating that C-4 treatment leads to reversal of the MDR phenotype resulting from an increased accumulation of anticancer drugs by inhibiting drug efflux function of P-gp. This notion is further supported by the observation that C-4 treatment potentiates paclitaxel-induced G(2)/M arrest of the cell cycle. In addition, the drug efflux function of P-gp was reversibly inhibited by C-4 treatment, while the expression level of P-gp was not affected. Collectively, our results describe the potential of C-4 to reverse the P-gp-mediated MDR phenotype through reversible inhibition of P-gp function, which may make it an attractive new agent for the chemosensitization of cancer cells. PMID- 17286967 TI - Synthesis of the four 1-(1-deoxy-D-pentitol-1-yl)thymines and conformational properties of the acyclic sugar chain. AB - Acetylated D-pentose diethyl dithioacetals were coupled by way of 1-bromo-1 ethylthio derivatives with 2,4-bis(trimethylsilyl)thymine to afford diastereomeric pairs of acyclic-sugar nucleoside analogues bearing a thymin-1-yl and an ethylthio group at C-1. Free-radical desulfurization by the action of tributylstannane removed the ethylthio group to afford the corresponding acetylated 1-(1-deoxy-d-pentitol-1-yl)thymines and subsequently the free title compounds in the arabino, lyxo, ribo, and xylo series. Conformations of the intermediates and products were studied in detail and the final products were evaluated for their potential as agents active against plant viruses and rice blast fungus. PMID- 17286968 TI - Innovative crystal transformation of dihydrate trehalose to anhydrous trehalose using ethanol. AB - The crystal transformation of dihydrate trehalose to anhydrous trehalose was investigated using ethanol and a new type of crystal particle with porous structure could be obtained. The specific surface area of the anhydrous crystal transformed at 50 degrees C was 3.3 m(2)/g, with a median pore diameter of 0.21 microm, and void volume of 0.22 mL/g. The crystal transformation was monitored by measuring the crystal moisture content. The crystal transformation rates could be correlated with the Avrami equation, using the mechanism parameter n=11.5, suggesting that the change of surface area occurred during crystal transformation from dehydrate to anhydrous trehalose. The apparent activation energy of the crystal transformation was 132 kJ/mol. PMID- 17286966 TI - Mechanism of dopamine mediated inhibition of neuropeptide Y release from pheochromocytoma cells (PC12 cells). AB - In rat pheochromocytoma (PC12) cells the dopamine D(2) receptor agonists apomorphine (APO) and n-propylnorapomorphine (NPA) produced a concentration dependent inhibition of K(+)-evoked neuropeptide Y release (NPY-ir). The effect of APO was blocked by the dopamine D(2)-receptor antagonist, eticlopride, but not the D(1)/D(3) or the D(4)/D(2) antagonists, SCH23390 or clozapine, respectively. The D(1)/D(5) receptor agonist, SKF38393 or the D(3) agonists PD128907 and 7-OH DPAT had no effect. Selective N and L-type voltage gated Ca(2+) channel blockers, omega-conotoxin GVIa (Ctx-GVIa) and nifedipine, respectively, produced a concentration dependent inhibition of NPY-ir release but were not additive with APO. The Ca(2+)/calmodulin-dependent protein kinase (CaM kinase) II inhibitor KN 62 produced a concentration-dependent inhibition of NPY-ir release but the combination of KN-62 and APO produced no further inhibition. PMA-mediated protein kinase C stimulation significantly increased both basal and K(+)-evoked release of NPY-ir, and in the presence of PMA APO had no inhibitory effect. The PKC antagonist, chelerythrine, inhibited K(+)-evoked NPY-ir release but was not additive with APO. Neither forskolin-mediated adenylate cyclase activation and the active cAMP analog Sp-cAMPS, nor the adenylate cyclase inhibitor SQ 22536, and the competitive inhibitor of cAMP-dependent protein kinases Rp-cAMPS, had any significant effect on K(+)-evoked NPY-ir release. This suggests the inhibitory effect of APO on K(+)-evoked release of NPY-ir from PC12 cells is most likely mediated through activation of dopamine D(2) receptors leading to direct inhibition of N and L-type voltage gated Ca(2+) channels, or indirect inhibition of PKC, both of which would reduce [Ca(2+)](i) and inactivate CaM kinase. PMID- 17286970 TI - Anchors aweigh: a demonstration of cross-modality anchoring and magnitude priming. AB - Research has shown that judgments tend to assimilate to irrelevant "anchors." We extend anchoring effects to show that anchors can even operate across modalities by, apparently, priming a general sense of magnitude that is not moored to any unit or scale. An initial study showed that participants drawing long "anchor" lines made higher numerical estimates of target lengths than did those drawing shorter lines. We then replicated this finding, showing that a similar pattern was obtained even when the target estimates were not in the dimension of length. A third study showed that an anchor's length relative to its context, and not its absolute length, is the key to predicting the anchor's impact on judgments. A final study demonstrated that magnitude priming (priming a sense of largeness or smallness) is a plausible mechanism underlying the reported effects. We conclude that the boundary conditions of anchoring effects may be much looser than previously thought, with anchors operating across modalities and dimensions to bias judgment. PMID- 17286969 TI - P2X7 receptor expression levels determine lethal effects of a purine based danger signal in T lymphocytes. AB - Contact of T lymphocytes with nicotinamide adenine dinucleotide (NAD) or ATP causes cell death that requires expression of purinergic receptor P2X(7) (P2X(7)R). T cell subsets differ in their responses to NAD and ATP, which awaits a mechanistic explanation. Here, we show that sensitivity to ATP correlates with P2X(7)R expression levels in CD4 cells, CD8 cells and CD4(+)CD25(+) cells from both C57BL/6 and BALB/c mice. But P2X(7)R ligands do not only induce cell death but also shedding of CD62L. It is shown here that in CD62L(high) T cells, CD62L shedding correlates with low expression of P2X(7)Rs and lower cell death, whereas in CD62L(low) cells P2X(7)R expression and death are higher. The possibility is therefore investigated that P2X(7)Rs induce T cell activation. Experiments show that spontaneous T cell proliferation is somewhat higher in cells expressing P2X(7)Rs, but this effect we suggest is caused by P2X(7)R expression on accessory cells. PMID- 17286971 TI - DNA damage and nitric oxide synthesis in experimentally infected Balb/c mice with Trypanosoma cruzi. AB - This study aimed to evaluate whether experimental Chagas disease in acute phase under benznidazole therapy can cause DNA damage in peripheral blood, liver, heart, and spleen cells or induce nitric oxide synthesis in spleen cells. Twenty Balb/c mice were distributed into four groups: control (non-infected animals); Trypanosoma cruzi infected; T. cruzi infected and submitted to benznidazole therapy; and only treated with benznidazole. The results obtained with the single cell gel (comet) assay showed that T. cruzi was able induce DNA damage in heart cells of both benznidazole treated or untreated infected mice. Similarly, T. cruzi infected animals showed an increase of DNA lesions in spleen cells. Regarding nitric oxide synthesis, statistically significant differences (p<0.05) were observed in all experimental groups compared to negative control, the strongest effect observed in the T. cruzi infected group. Taken together, these results indicate that T. cruzi may increase the level of DNA damage in mice heart and spleen cells. Probably, nitric oxide plays an important role in DNA damaging whereas benznidazole was able to minimize induced T. cruzi genotoxic effects in spleen cells. PMID- 17286972 TI - Effects of in vivo exposure to DEET on blood feeding behavior and fecundity in Anopheles quadrimaculatus (Diptera: Culicidae). AB - This study determined the effects of contact with DEET on guinea pig skin on mortality, probing time, blood feeding rate, engorgement time, and fecundity responses in female Anopheles quadrimaculatus Say. Exposure, in this manner, to 10% DEET (in ethanol) for 5 min, resulted in 98% mortality in mosquitoes after 24h. The median probing time (PT(50)) required by females, when exposed to 0.1%, 1.0%, and 10% DEET, was significantly (P<0.0001) longer (12.5, 12.1, and 19.1s, respectively) than the 6.8s required by females to probe ethanol-treated skin (control). Similarly, mean blood feeding rates in populations of females exposed to 1.0% DEET for < or = 5 min (14.4%) was 6x lower (P<0.001) (85.5%) than in females exposed to ethanol-treated skin, whereas the mean engorgement time on skin treated with 1.0% DEET (66.3s) was significantly shorter (P<0.0001) than for females feeding on the control guinea pigs (105.9s). The mean number of mature oocytes per female (fecundity) in treatment (1.0% DEET) and control mosquitoes was not significantly different. The responses to DEET observed in this study suggest that repeated exposure of female A. quadrimaculatus populations to this repellent, in laboratory bioassays, could result in confounding of toxicant and repellent effects and inaccurate estimates of DEET repellency. PMID- 17286973 TI - DNA polymerase beta catalytic efficiency mirrors the Asn279-dCTP H-bonding strength. AB - Ternary complexes of wild type or mutant form of human DNA polymerase beta (pol beta) bound to DNA and dCTP substrates were studied by molecular dynamics (MD) simulations. The occurrences of contact configurations (CC) of structurally important atom pairs were sampled along the MD trajectories, and converted into free-energy differences, DeltaG(CC). DeltaG(CC) values were correlated with the experimental binding and catalytic free energies for the wild type pol beta and its Arg183Ala, Tyr271Ala, Asp276Val, Lys280Gly, Arg283Ala, and Glu295Ala mutants. The correlation coefficients show that the strength of the H-bond between dCTP and Asn279 is a strong predictor of the mutation-induced changes in the catalytic efficiency of pol beta. This finding is consistent with the view that enzyme preorganization plays a major role in controlling DNA polymerase specific activity. PMID- 17286974 TI - Changes of PACAP levels in the brain show gender differences following short-term water and food deprivation. AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide exerting diverse actions in the central and peripheral nervous systems. A few studies indicate that PACAP is involved in the regulation of feeding and water homeostasis. The aim of the present study was to investigate changes in PACAP38 concentrations in different brain areas following food or water deprivation in male and female rats. Rats were sacrificed 12, 36 and 84h after water or food removal. PACAP levels were determined by radioimmunoassay. Our results show that levels of PACAP decreased in the hypothalamus in both sexes after water deprivation, with a more marked, significant decrease in females at 12h. A decrease was observed also in the telencephalon, with a similar pattern in both genders: levels were lowest after 12h, and showed a gradual increase at the other two time-points. PACAP levels increased in the brainstem of male rats, while females had a decrease 12h after water deprivation. The pattern of changes in PACAP levels was very different after food deprivation. In male rats, PACAP levels showed a significant increase in the hypothalamus, telencephalon and brainstem 12h after the beginning of starvation. In females, a less marked increase was observed only in the hypothalamus while no changes were found in the other brain areas. Our results show a sensitive reaction in changes of endogenous PACAP levels to water and food deprivation in most brain areas, but they are differentially regulated in male and female rats. PMID- 17286975 TI - Neuroendocrine control of growth hormone in fish. AB - The biological actions of growth hormone (GH) are pleiotropic, including growth promotion, energy mobilization, gonadal development, appetite, and social behavior. Accordingly, the regulatory network for GH is complex and includes many endocrine and environmental factors. In fish, the neuroendocrine control of GH is multifactorial with multiple inhibitors and stimulators of pituitary GH secretion. In fish, GH release is under a tonic negative control exerted mainly by somatostatin. Sex steroid hormones and nutritional status influence the level of brain expression and effectiveness of some of these GH neuroendocrine regulatory factors, suggesting that their relative importance differs under different physiological conditions. At the pituitary level, some, if not all, somatotropes can respond to multiple regulators. Therefore, ligand- and function specificity, as well as the integrative responses to multiple signals must be achieved at the level of signal transduction mechanisms. Results from investigations on a limited number of stimulatory and inhibitory GH-release regulators indicate that activation of different but convergent intracellular pathways and the utilization of specific intracellular Ca(2+) stores are some of the strategies utilized. However, more work remains to be done in order to better understand the integrative mechanisms of signal transduction at the somatotrope level and the relevance of various GH regulators in different physiological circumstances. PMID- 17286977 TI - Profiles of alpha-melanocyte-stimulating hormone in the Japanese flounder as revealed by a newly developed time-resolved fluoroimmunoassay and immunohistochemistry. AB - Profiles of alpha-melanocyte-stimulating hormone (alpha-MSH) in the Japanese flounder were examined by a newly developed time-resolved fluoroimmunoassay (TR FIA) and immunohistochemistry. A TR-FIA for alpha-MSH was newly developed, and its levels in the pituitary gland and plasma of Japanese flounder reared in a white or black tank for 5 months were compared. A competitive assay using two antibodies was performed among secondary antibodies in the solid phase, alpha-MSH antibodies, samples, and europium-labeled Des-Ac-alpha-MSH. The sensitivity of the assay, defined as twice the standard deviation at a zero dose, was 0.98 ng/ml (49 pg/well). The intra- and interassay coefficients of variation of the assay were 8.8% (n=8) and 17.3% (n=5), respectively, at about 50% binding. Cross reactivities of Des-Ac-alpha-MSH and Di-Ac-alpha-MSH were about 100%. Cross reactivities of adrenocorticotropic hormone, salmon gonadotropin-releasing hormone (sGnRH), and chicken GnRH-II were less than 0.2%, and that of melanin concentrating hormone was less than 2.0% at 50% binding. Displacement curves of serially twofold-diluted hypothalamus extract, pituitary gland extract, and plasma extract of Japanese flounder with the assay buffer were parallel to the alpha-MSH standard curve. Moreover, displacement curves of serially twofold diluted hypothalamus and/or pituitary gland extract of masu salmon, goldfish, red seabream, Japanese eel, tiger puffer, and barfin flounder with the assay buffer were also parallel to the alpha-MSH standard. In Japanese flounder, total immunoreactive (ir)-alpha-MSH levels in the pituitary gland were lower in the black tank, whereas those in the plasma tended to be higher in the black tank, suggesting that the synthesis and release of alpha-MSH are higher in the black tank. alpha-MSH-ir cells were detected in the pars intermedia and a small part of the pars distalis of the pituitary gland. alpha-MSH-ir cell bodies were located in the basal hypothalamus and alpha-MSH-ir fibers were distributed not only in the hypothalamus but also in the telencephalon, midbrain, cerebellum, and medulla oblongata, suggesting that alpha-MSH functions as a neuromodulator in the brain. PMID- 17286976 TI - Molecular evolution of neuropeptide receptors with regard to maintaining high affinity to their authentic ligands. AB - Recently, we cloned many of the bullfrog neuropeptide G protein-coupled receptors (GPCRs), including receptors for vasotocin (VT), mesotocin, gonadotropin releasing hormone (GnRH), neurotensin, apelin, and metastin. Bullfrog GPCRs usually have high affinity for bullfrog ligands but relatively low affinity for mammalian ligands. Reciprocally, synthetic agonists and antagonists developed based upon mammalian ligands display lower affinity at bullfrog receptors. Studies using chimeric or domain-swapped receptors indicate that the motifs responsible for differential ligand selectivity usually reside within transmembrane domain 6 (TMD6)-extracellular loop 3 (ECL3)-transmembrane domain 7 (TMD7). Triple mutation of mammalian V1aR (Phe(6.51) to Tyr, Ile(6.53) to Thr, and Pro(7.33) to Thr) increases VT affinity but greatly reduces arginine vasopressin affinity. This binding profile is similar to that of bullfrog VT1R. Changing just three amino acids in the bullfrog GnRH receptor-1 (i.e. Ser-Gln-Ser in the ECL3) to those found in the type-I mammalian GnRH receptor (i.e. Ser-Glu Pro) reverses GnRH selectivity. In conclusion, specific receptor motifs that govern ligand selectivity can be determined by comparative molecular analyses of GPCRs and their ligands. Such analysis provides clues for understanding how GPCRs maintain high affinity to their authentic ligands. PMID- 17286978 TI - Glucose-6-phosphate dehydrogenase activity in pre-eclampsia. PMID- 17286979 TI - Uterine artery embolization in the treatment and prevention of postpartum hemorrhage. AB - OBJECTIVES: The study was conducted to evaluate the efficacy of superselective transcatheter uterine artery embolization for control of obstetric hemorrhage. METHODS: Between January 2002 and December 2005, 14 consecutive patients underwent uterine artery embolization to control postpartum hemorrhage, and two to prevent hemorrhage before second-trimester therapeutic abortion. RESULTS: Embolization was performed by transfemoral arterial catheterization. Pieces of absorbable gelatin sponge were used in all cases, with the addition of platinum coils in two cases for complete vessel occlusion. Optimal bleeding control was achieved in all cases but one--a patient who underwent hysterectomy due to embolization failure. No severe complications were observed. CONCLUSIONS: The high success rate, low morbidity rate, and possibility of preserving reproductive function have made superselective uterine artery embolization the technique of choice to control life-threatening, intractable postpartum hemorrhage in hemodynamically stable patients, provided multidisciplinary medical teams are promptly available. PMID- 17286980 TI - Early identification in maternal blood of fetal sex in the presence of fetal DNA from previous pregnancies. PMID- 17286981 TI - Low-energy-loss EFTEM imaging of thick particles and aggregates. AB - Electron spectroscopy imaging is a powerful tool for the elucidation of colloidal particle morphology and microchemistry, but it normally requires the use of very thin samples, typically less than 50 nm, to avoid the effects of multiple scattering. This work shows that many aspects of the internal morphology of thick particles and aggregates and the chemical component distribution are revealed using low-energy-loss electron imaging in the transmission electron microscope, benefiting from multiple scattering as well as small but significant differences in the low-energy-loss spectra of aggregate constituents. Low-loss images reveal morphological details of thick aggregates made out of colloidal polymers (natural rubber and styrene-acrylic latex) and inorganic particles (silica, montmorillonite, and aluminum phosphate) at a spatial resolution close to that achieved in the bright-field images and much better than in the elemental maps, showing the advantages of the simultaneous use of low-loss images and standard thin-cut elemental maps. PMID- 17286982 TI - Transformations of gamma-alumina in aqueous suspensions 1. Alumina chemical weathering studied as a function of pH. AB - Hydration of gamma-Al2O3 is often reported to occur via the superficial transformation of the alumina surface into aluminum hydroxide-like layers. However, very little evidence has been given so far to support this hypothesis. It is demonstrated here by X-ray diffraction, TEM, electron diffraction, and solubility studies that a second process of hydration takes place that involves the dissolution of alumina and subsequent precipitation of well-shaped Al(OH)3 particles from supersaturated alumina aqueous solution. This process can be observed on a macroscopic scale (XRD, TEM) for any pH5, provided that the contact time between alumina and water exceeds 10 h. The least thermodynamically stable phase of aluminum hydroxide, bayerite, becomes favored compared with gibbsite when the pH of the solution is increased. It is assumed that the rate of formation of bayerite germs is greater than that of gibbsite due to variations in aluminum speciation in solution as a function of pH. PMID- 17286983 TI - Polypeptide multilayer films on colloidal particles: an in situ electro-optical study. AB - The buildup of poly(L-glutamic acid) (PGA) and poly(L-lysine) (PLL) multilayers on beta-FeOOH colloidal particles was investigated by means of electro-optics and electrophoresis. The films were built at different (acidic) pH in the absence of salt. We found that the thickness of the film grows linearly when the fully charged PLL (at pH 5.5) is combined with almost fully charged PGA (at pH 6.5), with a thickness of about 2 nm per single layer. When the fully charged PLL is combined with weakly charged PGA (at pH 4.5), the film thickness increases exponentially with the number of deposited layers. The thickness of the exponentially growing film increases to 300 nm after deposition of 16 layers. The exponential film growth is attributed to the ability of the PLL to diffuse "in" and "out" of the film bulk at each deposition step. The variation in the electrical polarizability of the film-coated particles was also monitored as a function of the number of adsorbed layers. The result reveals that the PLL chains, which can diffuse into the film bulk, have no measurable contribution to the electro-optical effect of the films terminated with PLL. It is only due to the polarization of counterions of the PLL adsorbed on the film surface. PMID- 17286984 TI - Formation of nanoparticles in water-in-oil microemulsions controlled by the yield of hydrated electron: the controlled reduction of Cu2+. AB - In the water-in-oil (W/O) microemulsions based on nonionic surfactants, i.e., Brij 30, Brij 56, or Triton X-100, the omega value (molar ratio of water to surfactant), anion, and surfactant could remarkably affect the radiolytic reduction of Cu2+ and the morphologies of the reduction products simultaneously. The addition of toluene or naphthalene could transform the reduction products from copper to cuprous oxide in the Brij 56-based microemulsion, and the efficiency of naphthalene was obviously higher than that of toluene. After the effects of pH value and cosurfactant were excluded, it could be concluded that the effects of the omega value, the anion, and the structure of the surfactant on the yield of hydrated electrons (eaq-) play a key role in the radiolytic reduction of Cu2+. It was also suggested that the morphology of the reduction product may be controlled by the yield of eaq-. PMID- 17286985 TI - Pain as the presenting symptom of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). AB - Numerous clinical forms of CIDP have been described, but pain is generally considered a rare or secondary sign. We describe here the clinical, electrophysiological and neuropathological characteristics of five patients with CIDP and pain as the main presenting symptom, and their course with treatment. Between January 2003 and December 2004, we selected five patients with prominent or isolated pain among 27 patients diagnosed with CIDP. All patients were subjected to clinical and electrophysiological examinations, and had a complete laboratory work up to exclude other causes of neuropathy. In view of the atypical clinical presentation, all five patients underwent nerve biopsy. There were two men and three women. The mean age at onset of neuropathy was 70+/-7.39 years. All patients initially presented with pain in the lower limbs associated with modest motor impairment (1 case), distal paresthesia (4 cases), cramps (1 case) and fatigue (2 cases). CSF was normal in three cases. On electrophysiological examination, three patients had nerve conduction abnormalities with subtle or clear signs of demyelination: three (case 1, 2 and 4) fulfilled the criteria of Rotta et al. and two (case 2 and 4) the criteria of both Nicolas et al and the INCAT group. Patients were all given symptomatic treatment and four patients received an immunomodulatory treatment, which was constantly effective. Pain may be a major and disabling symptom in patients with CIDP, so this diagnosis has to be considered in patients referred for a painful polyneuropathy. Moreover, immunomodulatory treatment has to be considered in such patients as symptomatic therapy may be ineffective. PMID- 17286986 TI - The dynamics of luminal depletion and the stochastic gating of Ca2+-activated Ca2+ channels and release sites. AB - Single channel models of intracellular calcium (Ca(2+)) channels such as the 1,4,5-trisphosphate receptor and ryanodine receptor often assume that Ca(2+) dependent transitions are mediated by constant background cytosolic [Ca(2+)]. This assumption neglects the fact that Ca(2+) released by open channels may influence subsequent gating through the processes of Ca(2+)-activation or inactivation. Similarly, the influence of the dynamics of luminal depletion on the stochastic gating of intracellular Ca(2+) channels is often neglected, in spite of the fact that the sarco/endoplasmic reticulum [Ca(2+)] near the luminal face of intracellular Ca(2+) channels influences the driving force for Ca(2+), the rate of Ca(2+) release, and the magnitude and time course of the consequent increase in cytosolic domain [Ca(2+)]. Here we analyze how the steady-state open probability of several minimal Ca(2+)-regulated Ca(2+) channel models depends on the conductance of the channel and the time constants for the relaxation of elevated cytosolic [Ca(2+)] and depleted luminal [Ca(2+)] to the bulk [Ca(2+)] of both compartments. Our approach includes Monte Carlo simulation as well as numerical solution of a system of advection-reaction equations for the multivariate probability density of elevated cytosolic [Ca(2+)] and depleted luminal [Ca(2+)] conditioned on each state of the stochastically gating channel. Both methods are subsequently used to study the role of luminal depletion in the dynamics of Ca(2+) puff/spark termination in release sites composed of Ca(2+) channels that are activated, but not inactivated, by cytosolic Ca(2+). The probability density approach shows that such minimal Ca(2+) release site models may exhibit puff/spark-like dynamics in either of two distinct parameter regimes. In one case, puffs/spark termination is due to the process of stochastic attrition and facilitated by rapid Ca(2+) domain collapse [cf. DeRemigio, H., Smith, G., 2005. The dynamics of stochastic attrition viewed as an absorption time on a terminating Markov chain. Cell Calcium 38, 73-86]. In the second case, puff/spark termination is promoted by the local depletion of luminal Ca(2+). PMID- 17286987 TI - Nicotine-induced vascular endothelial growth factor release via the EGFR-ERK pathway in rat vascular smooth muscle cells. AB - Cigarette smoke has been firmly established as an independent risk factor for atherosclerosis and other vascular diseases. The proliferation and migration of vascular smooth muscle cells (VSMC) induced by growth factors have been proposed to play an important role in the progression of atherosclerosis. In the present study, we investigated the effects of nicotine, which is one of the important constituents of cigarette smoke, on vascular endothelial growth factor (VEGF) release, in rat VSMC. The stimulation of cells with nicotine resulted in a time- and concentration-dependent release of VEGF. Hexamethonium, an antagonist of nicotinic acetylcholine receptor (nAChR), inhibited nicotine-induced VEGF release. We next investigated the mechanisms by which nicotine induces VEGF release in the cells. The nicotine-induced VEGF release was inhibited by treatment with U0126, a selective inhibitor of MEK, which attenuated the nicotine induced ERK phosphorylation. Nicotine induced a transient phosphorylation of ERK. Furthermore, AG1478, a selective inhibitor of epidermal growth factor receptor (EGFR) kinase, inhibited nicotine-induced ERK phosphorylation and VEGF release. These data suggest that nicotine releases VEGF through nAChR in VSMC. Moreover, VEGF release induced by nicotine is mediated by an EGFR-ERK pathway in VSMC. VEGF may contribute to the risk of cardiovascular diseases in cigarette smokers. PMID- 17286989 TI - Immune system expression of SLURP-1 and SLURP-2, two endogenous nicotinic acetylcholine receptor ligands. AB - A novel transduction pathway via which apoptosis of keratinocytes is regulated through nicotinic acetylcholine (ACh) receptors (nAChRs) has emerged in studies of secreted mammalian Ly6/urokinase plasminogen-type activator receptor-related protein-1 and-2 (SLURP-1 and SLURP-2, respectively). SLURP-1 reportedly binds to alpha7 nAChRs and enhances the amplitude of macroscopic currents induced by ACh, leading to facilitation of apoptosis, whereas SLURP-2 binds to alpha3 nAChRs and prevents apoptosis. These observations prompted us to test whether SLURPs are expressed in immune cells and are involved in the regulation of immune function. We initially used reverse transcription-polymerase chain reaction analysis to characterize the expression profiles of SLURP mRNAs in several murine tissues and organs. Although SLURP-1 mRNA was not expressed in the pancreas, all other tissues and organs tested, including spleen and thymus, expressed both SLURP-1 and SLURP-2 mRNAs. Expression of both mRNAs also was detected in T and B cells, bone marrow-derived dendritic cells (DCs) and macrophages. Moreover, as in keratinocytes, stimulation of MOLT-3 human leukemic T cells with recombinant human SLURP-1 evoked intracellular Ca(2+) signaling. These results suggest that both SLURP-1 and SLURP-2 are expressed in various immune cells and organs, and that not only ACh but also SLURPs may be involved in regulating lymphocyte function via nAChR-mediated pathways. PMID- 17286988 TI - Analysis of CD8+ T cell-mediated anti-viral responses in mice with targeted deletions of the M1 or M5 muscarinic cholinergic receptors. AB - A number of studies have demonstrated that non-neuronal acetylcholine can play a role in the regulation of T cell function. Recently, we reported that CD8(+) T cells, from mice with a targeted deletion of the M(1) muscarinic receptor, had a defect in differentiating into cytolytic T lymphocytes when stimulated in vitro. In the current report, we analyze the in vivo function of CD8(+) T cells from mice with targeted deletions of either M(1) or M(5) muscarinic receptors. M(1) or M(5) knockout mice were infected with either lymphocytic choriomeningitis virus or vesicular stomatitis virus. Expansion of anti-viral CD8(+) T cells was monitored by staining with tetramer reagents specific for the immunodominant peptides of the viruses. No defect in expansion of CD8(+) T cells was observed in either M(1) or M(5) knockout mice. The extent to which one can draw a generalized conclusion that M(1) and M(5) are not involved in anti-viral immunity depends upon issues of antigen strength, genetic background, induction of redundant receptors, and the potential for qualitative defects in the expanded CD8(+) T cells. PMID- 17286990 TI - The non-neuronal cholinergic system in peripheral blood cells: effects of nicotinic and muscarinic receptor antagonists on phagocytosis, respiratory burst and migration. AB - Peripheral blood cells express the complete non-neuronal cholinergic system. For example synthesis of acetylcholine and nicotinic as well muscarinic receptors have been demonstrated in leucocytes isolated from human peripheral blood. In the present experiments mononuclear cells and granulocytes were isolated from the peripheral blood to investigate content and synthesis of acetylcholine as well as phenotypic functions like respiratory burst, phagocytosis and migration. Mononuclear cells (T-cells and monocytes) contained 0.36 pmol/10(6) cells acetylcholine, whereas acetylcholine content in granulocytes was 100-fold lower. Acetylcholine synthesis amounted to 23.2+/-4.7 nmol/mg protein/h and 2.90+/-0.84 in CD15+ (granulocytes) and CD3+ cells (T-lymphocytes), respectively. Neither atropine (blockade of muscarinic receptors) nor tubocurarine (blockade of nicotinic receptors) exerted an effect on the respiratory burst. Tubocurarine (30 muM), alone or in combination with atropine (1 microM), reduced phagocytosis in granulocytes by 13% and 19%, respectively (p<0.05). Spontaneous transwell migration of granulocytes was doubled by tubocurarine combined with atropine (p>0.05). Also alpha-bungarotoxin (10 microg/ml) enhanced spontaneous granulocyte migration, but hexamethonium (300 microM) was without effect. The present experiments demonstrate a cholinergic modulation of immune functions in peripheral leucocytes under in vitro conditions, i.e. in the absence of a neuronal innervation. Blockade of nicotine receptors (alpha1 muscular subtype) facilitates spontaneous migration of granulocytes. PMID- 17286991 TI - Anti-inflammatory effects of a triterpenoid isolated from Wilbrandia ebracteata Cogn. AB - Wilbrandia ebracteata (WE), a Brazilian medicinal plant used in folk medicine for the treatment of rheumatic diseases, displays anti-inflammatory properties and constitutes a rich source of cucurbitacins and cucurbitacin-related compounds. The current study investigated the potential anti-inflammatory properties of Dihydrocucurbitacin B (DHCB), a cucurbitacin-derived compound isolated from roots of WE, in some in vivo and in vitro experimental models. Intraperitoneal treatment of mice with DHCB reduced both carrageenan-induced paw edema (0.3, 1 and 3 mg/kg caused inhibitions of 26, 44 and 56 % at 2 h after stimulation, respectively) and pleurisy (10 mg/kg inhibited leukocyte numbers and LTB(4) levels in the pleural fluid by 51 and 75% at 6 h after cavity challenge, respectively). In vitro, DHCB (up to 10 microg/mL) failed to modify LTB(4) production by human neutrophils or PGE(2) production by COS-7 cells transfected with COX-1, but PGE(2) production by COX-2 transfected COS-7 cells was markedly inhibited (by 72%). The levels of COX-1 or COX-2 proteins in IL-1alpha-stimulated NIH3T3 cells were unaffected by DHCB. The results corroborate the potential anti inflammatory properties ascribed to W. ebracteata Cogn. in folk medicine and suggest that they might be attributed, at least in part, to the capacity of one of this plants main constituents, DHCB, to inhibit COX-2 activity (but not its expression) during inflammation. PMID- 17286992 TI - Do visual illusions probe the visual brain? Illusions in action without a dorsal visual stream. AB - Visual illusions have been shown to affect perceptual judgements more so than motor behaviour, which was interpreted as evidence for a functional division of labour within the visual system. The dominant perception-action theory argues that perception involves a holistic processing of visual objects or scenes, performed within the ventral, inferior temporal cortex. Conversely, visuomotor action involves the processing of the 3D relationship between the goal of the action and the body, performed predominantly within the dorsal, posterior parietal cortex. We explored the effect of well-known visual illusions (a size contrast illusion and the induced Roelofs effect) in a patient (IG) suffering bilateral lesions of the dorsal visual stream. According to the perception-action theory, IG's perceptual judgements and control of actions should rely on the intact ventral stream and hence should both be sensitive to visual illusions. The finding that IG performed similarly to controls in three different illusory contexts argues against such expectations and shows, furthermore, that the dorsal stream does not control all aspects of visuomotor behaviour. Assuming that the patient's dorsal stream visuomotor system is fully lesioned, these results suggest that her visually guided action can be planned and executed independently of the dorsal pathways, possibly through the inferior parietal lobule. PMID- 17286993 TI - Redirection of anthocyanin synthesis in Osteospermum hybrida by a two-enzyme manipulation strategy. AB - Modern biotechnology has developed powerful tools for genetic engineering and flower colours are an excellent object to study possibilities and limitations of engineering strategies. Osteospermum hybrida became a popular ornamental plant within the last 20 years. Many cultivars display rose to lilac flower colours mainly based on delphinidin-derived anthocyanins. The predominant synthesis of delphinidin derivatives is referred to a strong endogenous flavonoid 3',5' hydroxylase (F3'5'H) activity. Furthermore, since dihydroflavonol 4-reductase (DFR) of Osteospermum does not convert dihydrokaempferol (DHK) to leucopelargonidin, synthesis of pelargonidin-based anthocyanins is naturally not realised. In order to redirect anthocyanin biosynthesis in Osteospermum towards pelargonidin derivatives, we introduced cDNAs coding for DFRs which efficiently convert DHK to LPg. But neither the expression of Gerbera hybrida DFR nor of Fragaria x ananassa DFR - the latter is characterised by an unusual high substrate preference for DHK - altered anthocyanin composition in flowers of transgenic plants. However, chemical inhibition of F3'5'H activity in ray florets of dfr transgenic plants resulted in the accumulation of pelargonidin derivatives. Accordingly, retransformation of a transgenic plant expressing Gerbera DFR with a construct for RNAi-mediated suppression of F3'5'H activity resulted in double transgenic plants accumulating predominantly pelargonidin derivatives in flowers. PMID- 17286994 TI - Anti-Candida metabolites from endophytic fungi. AB - Submerged cultures of some 1500 Ascomycota and Basidiomycota isolated from their fruit-bodies or as soil-borne, coprophilous or endophytic fungi were screened for activity against Candida albicans and a range of other pathogenic and saprotrophic fungi. Considerably more Ascomycota (11-16%) than Basidiomycota (3.5%) produced metabolites with activity against C. albicans. From five species of endophytes, six bioactive compounds were isolated and identified, viz. cerulenin (1), arundifungin (2), sphaeropsidin A (3), 5-(1,3-butadiene-1-yl)-3 (propene-1-yl)-2-(5H)-furanone (4), ascosteroside A (formerly called ascosteroside; 5) and a derivative of 5, ascosteroside B (6). 1, 3 and 5 were isolated from fungi belonging to different orders than previously described producers. Antifungal activities of 2 and 4-6 in the agar diffusion test were comparable with those of amphotericin B. Compound 6 exhibited a similar antifungal activity as 5 but its cytotoxicity towards Hep G2 cells was considerably lower. This study points to endophytic fungi related to hemibiotrophic or latent plant pathogens as an important source of bio- and chemodiversity. PMID- 17286995 TI - Genital chlamydial infection among male attendees at a sexually transmitted disease clinic in urban Taiwan. AB - OBJECTIVE: The aim of this study was to examine the epidemiology of genital Chlamydia trachomatis infection among male patients attending a sexually transmitted disease (STD) clinic in urban Taiwan. METHODS: From July 2003 to June 2004, all male attendees at an STD clinic were invited to participate in this study. Attendees provided a first-void urine sample for examination for C. trachomatis using polymerase chain reaction (PCR) assay. RESULTS: A total of 390 patients provided first-void urine specimens for testing for C. trachomatis. The overall prevalence of C. trachomatis was 17.7% (95% CI 16.3-19.1%). The age specific prevalence was higher among patients aged under 20 years and lowest among those aged over 30 years. Approximately 40% of the infections were asymptomatic or subclinical. Younger age (aged 7% at 25 degrees C and 1atm) resulted in an increasingly detrimental effect on the adsorption and photocatalytic decomposition rate of CB. Mechanistic analysis indicates that the relative hydrophilic/hydrophobic nature of a given chemical should dictate adsorption onto or penetration through water to the TiO(2) surface. It is suggested that multiple layers of water molecules are formed at the TiO(2) interface with air, even at low relative humidities. The multiple-layered film of water retards/prevents CB from reaching the reactive TiO(2) surface or contacting radical species in the boundary layer. PMID- 17287006 TI - Volatile chlorinated hydrocarbons in Antarctic superficial snow sampled during Italian ITASE expeditions. AB - In order to detect the presence of some volatile chlorinated hydrocarbons (VCHCs) and to understand their transport and deposition mechanism, superficial snow was sampled during two Italian ITASE (International Trans Antarctic Scientific Expedition) expeditions: the first traverse was carried out in 1998/1999 from Terra Nova Bay to Dome Concordia; the second traverse was carried out in 2001/2002 through Adelie, George V, Oates and Northern Victoria Lands. Some VCHCs (chloroform; 1,1,1-trichloroethane; tetrachloromethane; 1,1,2-trichloroethylene; tetrachloroethylene) were analysed using a highly sensitive and selective hyphenated technique composed of a purge-and-trap injector coupled to a gas chromatograph with a mass spectrometric detector (PTI-GC-MS) operating in SIM mode. Investigated VCHCs were present in all analysed snow samples with concentration levels of several units, tens, or sometimes hundreds of ng kg(-1). VCHC snow concentration levels remained approximately constant with changing distance from the coast and the comparison between fresh and aged snow did not show any substantial differences; on the basis of this evidence marine aerosol and dry deposition may be rejected as principal VCHC transport and deposition mechanism hypotheses. VCHC concentration levels in Antarctic snow samples were comparable to or greater than those found in snow from temperate zones. PMID- 17287007 TI - Temporal variability in particle-associated pesticide exposure in a temporarily open estuary, Western Cape, South Africa. AB - This study assesses the risk of current-use pesticides in a temporarily open estuary in South Africa by developing probabilistic risk estimates. Particle associated pesticides (chlorpyrifos, prothiofos, cypermethrin, fenvalerate, endosulfan and p,p-DDE) and physicochemical parameters (salinity, temperature, flow, and total organic content (TOC)) were measured in the Lourens River estuary (Western Cape) twice a month over a period of two years and equilibrium partitioning theory was applied to calculate concentrations of pesticides in the water. The 90th percentile concentrations of pesticides associated to suspended particles and the calculated concentrations in water were 34.0microg kg(-1) and 0.15microg l(-1) for prothiofos, 19.6microg kg(-1) and 0.45microg l(-1) for chlorpyrifos and 18.6microg kg(-1) and 0.16microg l(-1) for endosulfan. Highest average concentrations were found around the summer season due to higher application rates and as a result of the low flow during this season. Species sensitivity distribution indicated a 1.5-2.8 times higher toxicity (hazardous concentration HC5) for marine organisms compared to freshwater organisms. The calculated concentrations in the water exceeded all threshold values suggested by international water guidelines. Chlorpyrifos and endosulfan posed the highest acute risk to the Lourens River estuary. No sufficient toxicity data and threshold values were found for prothiofos. PMID- 17287008 TI - VOC destruction by water diluted hydrogen mild combustion. AB - This study represents a preliminary numerical evaluation of the effect of steam dilution and hydrogen addition on the oxidation of formaldehyde and benzene, chosen as representative of the volatile organic compounds (VOC), in mild condition by evaluating the autoignition time and the steady state attainment. These parameters are important in the design of thermal VOC destruction plants since they influence the abatement efficiency and, therefore, the plant dimension. It has come out that, in comparison with the system diluted in nitrogen, steam induces lower autoignition times and, on the other hand, longer times for the attainment of the steady state. In contrast, for very high water content the autoignition time slightly increases. In particular results have shown that is possible to identify an optimum value of steam content that allows for the attainment of the steady state condition by the lowest residence time. Hydrogen addition to systems diluted in nitrogen promotes the oxidation reactions and anticipates the steady state condition. In steam diluted systems hydrogen delays the autoignition of the mixtures even though anticipates the attainment of the complete destruction of the VOC. The rate of production analysis has showed that the H(2)/O(2) reactions, that promote the ignition and the destruction of VOC, are sensibly modified by the presence of water and hydrogen. PMID- 17287010 TI - Evolution of some physical properties related to soil quality in the degraded ecosystems of "rana" formations from SW Spain. AB - The dynamics of some physical properties of the soil: bulk density, porosity and percentage of water stable aggregates, which usually are taken as indicators for evaluation of soil quality, have been studied on the flat surfaces of the Canamero's "rana" formation (Caceres, SW Spain). The study shows a high relationship between all these physical soil parameters, the degradation level of the natural vegetation, and years of the soil under tillage. As the deterioration of the natural soil increases the bulk density of the fine earth is increased, diminishing porosity, field capacity moisture content, percentage of water stable aggregates in soil and water infiltration. PMID- 17287009 TI - Impact of climate variability on tropospheric ozone. AB - A simulation with the climate-chemistry model (CCM) E39/C is presented, which covers both the troposphere and stratosphere dynamics and chemistry during the period 1960 to 1999. Although the CCM, by its nature, is not exactly representing observed day-by-day meteorology, there is an overall model's tendency to correctly reproduce the variability pattern due to an inclusion of realistic external forcings, like observed sea surface temperatures (e.g. El Nino), major volcanic eruption, solar cycle, concentrations of greenhouse gases, and Quasi Biennial Oscillation. Additionally, climate-chemistry interactions are included, like the impact of ozone, methane, and other species on radiation and dynamics, and the impact of dynamics on emissions (lightning). However, a number of important feedbacks are not yet included (e.g. feedbacks related to biogenic emissions and emissions due to biomass burning). The results show a good representation of the evolution of the stratospheric ozone layer, including the ozone hole, which plays an important role for the simulation of natural variability of tropospheric ozone. Anthropogenic NO(x) emissions are included with a step-wise linear trend for each sector, but no interannual variability is included. The application of a number of diagnostics (e.g. marked ozone tracers) allows the separation of the impact of various processes/emissions on tropospheric ozone and shows that the simulated Northern Hemisphere tropospheric ozone budget is not only dominated by nitrogen oxide emissions and other ozone pre-cursors, but also by changes of the stratospheric ozone budget and its flux into the troposphere, which tends to reduce the simulated positive trend in tropospheric ozone due to emissions from industry and traffic during the late 80s and early 90s. For tropical regions the variability in ozone is dominated by variability in lightning (related to ENSO) and stratosphere-troposphere exchange (related to Northern Hemisphere Stratospheric dynamics and solar activity). Since tropospheric background chemistry is regarded only, the results are quantitatively limited with respect to derived trends. However, the main results are regarded to be robust. Although the horizontal resolution is rather coarse in comparison to regional models, such kind of simulations provide useful and necessary information on the impact of large-scale processes and inter annual/decadal variations on regional air quality. PMID- 17287011 TI - A simple methodology for the evaluation of groundwater pollution risks. AB - Groundwater represents a very significant source of fresh water for irrigation and drinking purposes and therefore preserving the availability and quality of this resource is extremely important. A first assessment of the amount of pollutants that can be exported to groundwater via soil drainage can be made by a) measuring the amount of contaminants present in the soil solution at the bottom of the soil after a prolonged simulated rainfall event, and b) estimating the amount of drainage water passing the soil bottom during a period of time long enough to include sufficient instances of both, wet and dry episodes inherent to the local climate. Drainage water was estimated by means of a simple infiltration model ("bucket model") which computes on a daily basis the inputs and outputs of soil water through rainfall and evapotranspiration generated by a stochastic model of the local climate along a period of 50-100 years. The methodology was applied in the Guadiamar valley after the toxic spill of a pyrite mine in Aznalcollar (Spain). The results show that Zn is the dominant contaminant at the site with a 1.2 g m(-2)year(-1) contribution to groundwater. The presence of a gravel rich horizon below 50 cm depth reveals an increase in drainage and the threat to groundwater. PMID- 17287012 TI - Relationships between ten-year trends of tropospheric ozone and temperature over Taiwan. AB - The analyses of ten-year ozonesonde observations from 1993 till 2002, over Taipei, Taiwan show influences of climate change. Despite huge increases in its precursor emissions in this region, there were little variations in tropospheric ozone. Results indicate a warmer troposphere, a statistically insignificant rising tropopause, 79+/-206 m per decade, and decreasing tropopause temperature at -1.0+/-0.89 K per decade. The derived mean tropospheric ozone is 40.58+/-10.99 DU, and has a statistically insignificant small trend of -0.78+/-1.7 DU per decade. The derived ten-year vertical trends of temperature and ozone are inversely correlated with each other from the middle troposphere up to the lower stratosphere. The averaged monthly vertical temperature trends show a generally warmer middle troposphere. The tropospheric ozone monthly trend has small increases only in the lower troposphere during winter and spring. Strong decreases occur in summer, from the surface up into the stratosphere. For ozone variation, results suggest that influences of climate forcing are stronger than those from precursor increases. More frequent and/or intense convection in summer and other climate-induced effects may contribute to the less than expected ozone observed in the troposphere. PMID- 17287013 TI - Total copper content and its distribution in acid vineyards soils developed from granitic rocks. AB - Total and extractable (5 extractants) Cu concentrations were determined in thirteen acid vineyards soils. Mean total copper concentration was 259 mg kg(-1) and most of the soil samples (87%) were above the upper limit allowed by the European Union for this element in soils. The largest Cu fraction was found to be that bound to soil organic matter, which accounted for 49% of the total Cu. None of the Cu fractions showed significant differences with depth. Nevertheless, bioavailable Cu (extracted in Na(2)-EDTA) was found to show a strong correlation with Cu bound to soil organic matter, which may indicate that Na(2)-EDTA is able to extract part of the organically bound Cu, resulting in an overestimation of bioavailable Cu. However, practices associated to soil use change and management affecting the stability of Cu organic complexes could induce an increase in bioavailable Cu levels in these soils. PMID- 17287014 TI - Soil management effects on aggregate dynamics in semiarid Aragon (NE Spain). AB - During decades, in semiarid rainfed Aragon, intensive soil tillage and low crop residue input have led to the loss of soil structure and soil degradation. Conservation tillage and cropping intensification can improve soil structure in these areas. The objective of this study was to determine the influence of three different tillage systems (traditional tillage, reduced tillage and no-tillage) under two cropping systems (fallow-barley rotation and barley monoculture) on soil aggregation dynamics during a cropping season. A decrease in tillage intensity resulted in a higher mean size of dry aggregates and a greater water aggregate stability in both cropping systems particularly under no-tillage. PMID- 17287015 TI - Performance of a high-volume cascade impactor in six European urban environments: mass measurement and chemical characterization of size-segregated particulate samples. AB - The performance of a modified Harvard high-volume cascade impactor (HVCI) was evaluated in six field campaigns with size-segregated particulate samplings for chemical and toxicological characterization. The 7-week sampling campaigns in 2002-2003 in Duisburg (autumn), Prague (winter), Amsterdam (winter), Helsinki (spring), Barcelona (spring), and Athens (summer) were selected to represent contrasting urban environments and seasons of public health interest due to high particulate concentrations or previous findings in epidemiological studies. Particulate samples were collected in parallel with the HVCI (PM(10-2.5), PM(2.5 1), PM(1-0.2), PM(0.2)), a virtual impactor (VI; PM(10-2.5), PM(2.5)), and a Berner low-pressure impactor (BLPI; 10 stages between 0.035 and 10 mum in particle diameter) using a 3- or 4-day sampling duration. The campaigns exhibited different profiles with regard to particulate mass concentration, size distribution, chemical composition and meteorological conditions, thus providing a demanding setup for an overall field comparison of the HVCI with the VI and BLPI reference samplers. Size-segregated particulate mass concentration could be reasonably well measured with the present HVCI configuration. The coarse (PM(10 2.5)) and fine (PM(2.5)) particulate mass agreed within 10% with the low-volume reference samplers, and the four-stage size distribution of the HVCI followed the modal pattern of urban aerosol. The concentrations of chemical constituents measured and integrated especially for the HVCI-PM(2.5) differed to some extent from those measured from the corresponding VI-PM(2.5) samples. This implies that when investigating the association of toxicological responses with the chemical constituents of particulate matter, it is necessary to use the chemical composition data of the same samples as used in toxicological experiments. PMID- 17287016 TI - Platelet activation in acute, decompensated congestive heart failure. AB - BACKGROUND: Congestive heart failure (CHF) is associated with increased risk of venous thromboembolism, stroke and sudden death. This may be related to abnormalities of thrombogenesis and platelet activation. A comprehensive assessment of platelet (dys)function in acute decompensated heart failure (AHF) is lacking, and we hypothesised that such patients would show greater abnormalities in platelet indices, compared to stable CHF and healthy controls. METHODS: We measured soluble P-selectin (sP-sel, by ELISA); platelet surface P selectin (CD62P%G) and CD63%G expression by flow cytometry; and platelet structural indices [mean platelet volume (MPV), mean platelet mass (MPM) and mean platelet component (MPC)] in 22 patients with AHF (pre- and posttreatment), who were compared to 68 patients with stable congestive heart failure (CHF, all with left ventricular ejection fraction (LVEF) <50%) and 23 healthy controls. RESULTS: There were significant differences between the 3 study groups in MPV (p<0.001), MPC (p=0.001), platelet surface P-selectin (CD62P%G, p<0.0001) and platelet surface CD63P%G (p=0.017). On post-hoc analyses, AHF patients had higher platelet surface P-selectin (CD62P%G) compared to stable CHF patients and healthy controls (Tukey's test, all p<0.05), whilst CD63%P was similarly high in both disease groups, compared to healthy controls. Platelet surface P-selectin (p=0.032), CD63 (p=0.024) and CD40L (p=0.024) were significantly reduced following treatment of AHF, though platelet morphology and sP-sel levels were not significantly changed. CONCLUSION: AHF patients demonstrate some abnormalities of platelet activation compared to stable CHF patients and healthy controls. These platelet abnormalities are modified by treatment, raising the possibility that platelets may partly contribute to the pathophysiology of adverse complications associated with AHF. PMID- 17287017 TI - Taurine ameliorates stress-induced degeneration of the urinary bladder. AB - We studied the potential effects of taurine, a free radical scavenger, on chronic water avoidance stress (WAS)-induced degeneration of the mucosa of the urinary bladder in experimental rats. Wistar albino rats were exposed to WAS for 2h/day, for 5 days (WAS group). Before exposing them to WAS, taurine (50mg/kg) (WAS+taurine group) was injected intraperitonally into the animals. Samples of urinary bladder were then investigated by light and scanning electron microscopy. Lipid peroxidation and gluthathione levels were also measured in the urinary bladder. In the WAS-only group, inflammatory cell infiltration, increased number of mast cells in the mucosa and ulcerated areas were observed. In the WAS+taurine group, relatively normal urothelial topography with microvilli, moderate inflammatory cell infiltration and decreased numbers of mast cells in the mucosa were observed. The increased lipid peroxidation and decreased glutathione levels in WAS rats were reversed by taurine treatment. We conclude that taurine protects against WAS-induced oxidant urinary bladder injury, and thus may be a possible therapeutic agent against interstitial cystitis, the symptoms of which are aggravated by stress conditions. PMID- 17287018 TI - Nodularin induces oxidative stress in the Baltic Sea brown alga Fucus vesiculosus (Phaeophyceae). AB - In the Baltic Sea regular, intensive cyanobacterial blooms rich in the cyanobacterium Nodularia spumigena occur during the summer season. N. spumigena is known to produce the cyclic pentapeptide nodularin (NOD) in high concentrations. Marine macroalgae, together with sea-grass meadows, are an extremely important habitat for life in the sea. In addition to this, the decaying macroalgae substantially contribute to the substrate for the microbial loop in coastal food webs. Uptake of nodularin into the brown macroalga Fucus vesiculosus was assessed using an ELISA technique resulting in an uptake of up to 45.1 microg kg(-1) fresh weight (fw). Nodularin was also detected in the reproductive part of the algae (receptacle) at 14.1 microg kg(-1) fw. The induction of oxidative stress in F. vesiculosus, after exposure to NOD, was also shown by monitoring cellular damage as changes in lipid peroxidation and the activation of antioxidative defence systems (antioxidative capacity, superoxide dismutase and soluble glutathione S-transferase). PMID- 17287019 TI - Identification of immune-relevant genes in histoincompatible rejecting colonies of the tunicate Botryllus schlosseri. AB - The colonial ascidian Botryllus schlosseri manifests a unique allorecognition system that is controlled by a single histocompatibility haplotype, the Fu/HC locus. When two allogeneic incompatible colonies come into direct contact, they develop inflammatory-like rejection lesions, called points of rejection (POR). While screening for differentially expressed genes during POR formation, we developed and analyzed a cDNA library of expressed sequence tags (ESTs) with 1693 unique ESTs that were clustered and assembled into 217 contigs and 1476 singlets. About 51% of these ESTs showed high similarity (E-value 0.005) to known database sequences, of which 123 matches were identified as immune-relevant genes encoding for stress proteins, pattern recognition receptors and complement proteins, proteases and protease inhibitors, cell adhesion and coagulation proteins, cytokine-related proteins, programmed cell death and proteasome-associated proteins. This first EST wide-screening analysis of the Botryllus allorecognition effector arm reveals a complex innate immune system, hallmarked by a whole genome response to allorecognition challenge. PMID- 17287020 TI - Preliminary characterization of hemolymph coagulation in Anopheles gambiae larvae. AB - Hemolymph coagulation is a first response to injury, impeding infection, and ending bleeding. Little is known about its molecular basis in insects, but clotting factors have been identified in the fruit fly Drosophila melanogaster. Here, we have begun to study coagulation in the aquatic larvae of the malaria vector mosquito Anopheles gambiae using methods developed for Drosophila. A delicate clot was seen by light microscopy, and pullout and proteomic analysis identified phenoloxidase and apolipophorin-I as major candidate clotting factors. Electron microscopic analysis confirmed clot formation and revealed it contains fine molecular sheets, most likely a result of lipophorin assembly. Phenoloxidase appears to be more critical in clot formation in Anopheles than in Drosophila. The Anopheles larval clot thus differs in formation, structure, and composition from the clot in Drosophila, confirming the need to study coagulation in different insect species to learn more about its evolution and adaptation to different lifestyles. PMID- 17287021 TI - Drosophila C-type lectins enhance cellular encapsulation. AB - C-type lectins are calcium-dependent carbohydrate binding proteins, and animal C type lectins participate in innate immunity and cell-cell interactions. In the fruit fly Drosophila melanogaster, more than 30 genes encode C-type lectin domains. However, functions of Drosophila C-type lectins in innate immunity are not well understood. This study is to investigate whether two Drosophila C-type lectins, CG33532 and CG33533 (designated as DL2 and DL3, respectively), are involved in innate immune responses. Recombinant DL2 and DL3 were expressed and purified. Both DL2 and DL3 agglutinated Gram-negative Escherichia coli in a calcium-dependent manner. Though DL2 and DL3 are predicted to be secreted proteins, they were detected on the surface of Drosophila hemocytes, and recombinant DL2 and DL3 also directly bound to hemocytes. Coating of agarose beads with recombinant DL2 and DL3 enhanced their encapsulation and melanization by Drosophila hemocytes in vitro. However, hemocyte encapsulation was blocked when the lectin-coated beads were pre-incubated with rat polyclonal antibody specific for DL2 or DL3. Our results suggest that DL2 and DL3 may act as pattern recognition receptors to mediate hemocyte encapsulation and melanization by directly recruiting hemocytes to the lectin-coated surface. PMID- 17287022 TI - In utero exposure to DDT and performance on the Brazelton neonatal behavioral assessment scale. AB - We investigated whether decrements in neonatal neurodevelopment, as determined by the Brazelton neonatal behavioral assessment scale (BNBAS), were associated with in utero exposure to dichlorodiphenyltrichloroethane (DDT): p,p'-dichlorodiphenyl trichloroethane (p,p'-DDT), o,p'-dichlorodiphenyl trichloroethane (o,p'-DDT) and p,p'-DDT's primary breakdown product p,p'-dichlorodiphenyl dichloroethylene (p,p' DDE) (heretofore collectively referred to as DDT/DDE). Our subjects were a birth cohort of 303 infants whose mothers were low-income Latinas living in the Salinas Valley, an agricultural community in California. We assessed neonates < or =2 months old using the seven BNBAS clusters (habituation, orientation, motor performance, range of state, regulation of state, autonomic stability, and reflex) and examined performance in relationship to DDT/DDE measures in maternal serum samples collected during pregnancy. We did not find any detrimental associations between in utero DDT/DDE levels and neonatal performance on the BNBAS. In this same cohort, we previously demonstrated that exposures to DDT/DDE were related to decrements in neurodevelopment at 6-24 months of age. The failure to observe effects on the BNBAS in these same children may be due to limited sensitivity of a single BNBAS assessment or a delay in the manifestations of neurodevelopmental effects of DDT/DDE until after the neonatal period. PMID- 17287024 TI - Simple Windows-based software for the control of laser scanning confocal microscopes. AB - Rapid advances in computer processing power and the appearance of low cost, high speed multifunction data acquisition hardware makes the control of confocal laser scanning microscopes (CLSMs) with standard laboratory hardware a potentially straightforward task. This paper describes software designed to control a Biorad MRC 600 scan head under Windows 2000 or XP. Using a single high speed, multifunction data acquisition board running under the Igor Pro software environment, waveforms required to drive the scan head galvanometers can be generated and up to two channels of images (768 x 512 pixels at 8 or 12 bit levels) captured live or at set intervals. Image averaging, zooming, panning and cropping are supported as is live region of interest measurements over time. The software can trigger or be triggered by external devices via TTL signals and, with the addition of a commercial focus controller, Z scans can also be made. Control of the original neutral density and emission filters of multiple laser based systems is also supported via serial control. The software should be easily adaptable to control custom designed scanning systems or other older makes of CLSM and it can be integrated with additional acquisition boards for simultaneous electrophysiological recording. PMID- 17287023 TI - Lipid-lowering therapy with statins, a new approach to antiarrhythmic therapy. AB - Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) are the most effective and best-tolerated drugs to treat elevated levels of low density lipoprotein cholesterol (LDL-C). In addition, they exhibit other effects unrelated to their lipid lowering effects (pleiotropic actions). In recent years, experimental and clinical evidence demonstrates that statins exert antiarrhythmic properties, reducing the recurrences of supraventricular and life-threatening ventricular arrhythmias both in patients with and without coronary artery disease (CAD). Thus, statins may constitute a novel therapeutic approach to cardiac arrhythmias. This article reviews the antiarrhythmic properties of statins as well as the possible mechanisms involved, including the lowering of LDL-C levels, the improvement of endothelial dysfunction and autonomic function, the stabilization of the atherosclerotic plaques, the antioxidant, antiinflammatory, antithrombotic and cardioprotective properties and the modulation of transmembrane ion fluxes. PMID- 17287025 TI - Measurement of neuronal activity of individual neurons after stroke in the rat using a microwire electrode array. AB - BACKGROUND AND PURPOSE: Ischemic stroke induces spreading depression of brain waves and ischemic depolarizations, suggesting electrical activity of neurons is sensitive to stroke. The present study was designed to measure the electrophysiological response of an array of individual neurons to ischemic stroke in rats. METHODS: A custom-made microwire electrode array (16 channels) was implanted in the cortical area supplied by the middle cerebral artery, spanning the core and boundary of the ischemic lesion. The electrophysiological activity of individual neurons was simultaneously recorded before, during and one week after middle cerebral artery occlusion (MCAo). RESULTS: Neuronal activities were significantly reduced immediately after MCAo. Intermittent silent periods (SP) appeared within minutes or hours after MCAo and lasted variable times. Between intermittent SP, neurons fired irregular bursting spikes (BS) with small magnitudes. Intermittent SP and irregular BS progressed in one day post stroke to persistent SP in channels close to the ischemic core or to regular BS with small amplitudes in the penumbral zone. Both persistent SP and regular BS persisted for at least seven days. CONCLUSIONS: Electrode array can be used to simultaneously record multiple individual neurons in response to ischemic stroke. This study provides the first evidence that the primary electrophysiological activity of multiple individual neurons to ischemic stroke is reduced in the lesion boundary and/or stopped in and adjacent to the lesion core. PMID- 17287026 TI - Neurochemical and behavioral consequences of striatal injection of 5,7 dihydroxytryptamine. AB - It is known that central serotonin (5HT) is involved in anxiety, but the behavioral results of many studies have been inconsistent. A prevalent research approach is to destroy 5HT neurotoxically. Such lesions were mostly generated by injecting 5,7-dihydroxytryptamine into ventricles or raphe nuclei, leading to rather global losses of 5HT in the brain. However, there is evidence for differential effects of 5HT in different brain structures regarding anxiety. Therefore, we decided to study the effects of injecting 5,7-dihydroxytryptamine into the forebrain. We chose the ventral striatum as the site of injection, since there is evidence that 5HT may be involved in anxiety there. We administered the neurotoxin bilaterally in adult rats, and analyzed neurochemical and behavioral consequences in three experiments. The first one showed that the toxin dose dependently (10-50 microg) depleted 5HT in the ventral striatum, neostriatum, frontal cortex, and amygdala. Besides 5HT, dopamine was also partly depleted there. This dopaminergic lesion was prevented in a second experiment, where rats were pre-treated systemically with the dopamine reuptake inhibitor nomifensine. In the final experiment, the functional consequences of such 5HT lesions were tested, which yielded moderate anxiogenic effects in the elevated plus maze and in the open field. Also, there were lesion effects on aversively motivated ultrasonic vocalization during an active avoidance test. In contrast, active avoidance performance itself and general activity in the open field were not affected. Lesion effects became discernible there when challenging rats with MDMA. The psycho-stimulatory effectiveness of this drug, which acts largely via the availability of 5HT in the brain, was reduced to degrees that depended on the size of 5HT lesion. These results are discussed with respect to factors such as severity of lesion, anatomical specificity, and the role of 5HT in anxiety. PMID- 17287027 TI - Psychosis-proneness and socially relevant reasoning. AB - Reasoning biases have been suggested as having a role in the formation and maintenance of delusions, in particular when the content is personal or social. The present study investigated whether biases when making logical inferences about neutral and personally relevant statements may be seen in individuals hypothetically prone to psychosis. Sixty-one participants completed a multi dimensional measure of psychosis-proneness (Oxford-Liverpool Inventory of Feelings and Experiences) and a conditional inference task. It was found that highly anhedonic participants made more invalid inferences both when reasoning about the consequences of others' emotions and implications for their own self state. Impulsive Non-conformity was also associated with poor reasoning when 'deducing consequences from others emotions'. The findings suggest that individuals with impulsive and/or anhedonic traits may tend to ignore alternative information when reasoning about personally relevant emotional statements leading to poorer reasoning. PMID- 17287028 TI - Associations between schizotypal personality traits and the facilitation and inhibition of the speed of contextually cued responses. AB - This study measured schizotypal personality traits in a sample of 33 healthy participants using the Oxford-Liverpool Inventory of Feelings and Experiences. These traits were correlated with measures of inhibition and facilitation of response times (RTs) within a cued letter-comparison task. It was expected that scores on a measure of positive schizotypy, reflecting unrealistically distorted perceptions and beliefs, would be negatively associated with inhibition of RTs to targets that were unexpected in the context of the preceding letter cue. No specific predictions were made for the facilitation of RTs to targets expected in the context of the cues. The predicted negative association for positive schizotypy and inhibition of RTs was confirmed. There was no significant association between positive schizotypy and facilitation of RTs; however, there was an unpredicted finding that facilitation of RTs was increased in individuals with higher levels of disorganized schizotypy. The findings for positive schizotypy were consistent with Hemsley's model, in that high positive schizotypy results from a weakening of contextually elicited inhibitory processes, and is associated with altered functioning of a monitoring system. The normal functioning of the monitoring system is to generate mismatch signals that interrupt information processing when a contextually unexpected stimulus occurs. PMID- 17287029 TI - Clinical value of anti-Leishmania (Leishmania) chagasi IgG titers detected by flow cytometry to distinguish infected from vaccinated dogs. AB - Leishmune vaccination covers a broader number of endemic areas of canine visceral leishmaniasis (CVL) and therefore the development of new serological devices able to discriminate CVL from Leishmune vaccinees becomes an urgent need considering the post-vaccine seroconversion detected throughout conventional methodologies. Herein, we have described the establishment of a flow cytometry based methodology to detect anti-fixed L. (L.) chagasi promastigotes antibodies (FC-AFPA-IgG, FC AFPA-IgG1 and FC-AFPA-IgG2) in sera samples from Leishmania (Leishmania) chagasi infected dogs and Leishmune vaccinees. The results of FC-AFPA were reported along the sera titration curve (1:128-1:524,288), as percentage-of-positive-fluorescent parasite (PPFP). The use of PPFP=20% as a cut-off edge to segregate negative and positive results at sera dilution 1:2048 revealed outstanding performance indexes that elect FC-AFPA-IgG and IgG2 (both detected by polyclonal FITC-labeled second step reagent) applicable to the serological diagnosis of CVL, with 100% of specificity for both IgG and IgG2 and 97 and 93% of sensitivity, respectively. Moreover, FC-AFPA-IgG, applied at sera dilution 1:2048, also appeared as a useful tool to discriminate L. chagasi infected dogs from Leishmune vaccinees, with 76% of specificity. Outstanding likelihood indexes further support the performance of FC-AFPA-IgG for exclusion diagnosis of CVL in Leishmune vaccinees. Analysis of FC AFPA-IgG at sera dilution 1:8192 revealed the most outstanding indexes, demonstrating that besides the ability of PPFP or=30.2 cm3 (diameter approximately 4 cm) and or having any overlap with hilum, the median EUDs were 9.6, 22.6, and 62.9 Gy for ipsilateral lower paratracheal, subcarinal, and ipsilateral hilar regions, respectively. The corresponding median V40 were 32.5%, 39.3%, and 97.6%, respectively. CONCLUSIONS: Although incidental nodal irradiation dose is low in the whole group, the dose to high-risk nodal regions is considerable in patients with T1-3N0 NSCLC when the primary is large and/or centrally located. PMID- 17287042 TI - Current topics in food microbiology. PMID- 17287041 TI - A cholinergic model synapse to elucidate protein function at presynaptic terminals. AB - A large number of proteins have been identified at nerve terminals and a cascade of protein-protein interactions has been suggested to be involved in cycling of synaptic vesicle states. To explore protein function in presynaptic terminals, only a few unique synapses such as the squid giant synapse, the calyx of Held synapse and the hippocampal neuron autapse have been used. The squid giant synapse and the calyx of Held are useful to introduce reagents into their large presynaptic terminals and the hippocampal neuron autapse is a good system to modify a protein level by exogenous DNA or RNA. The cholinergic synapse formed between superior cervical ganglion (SCG) neurons in long-term culture is a useful model for a fast synapse. The axon of the large cell body contacts with soma of neighboring neurons. The architecture of synaptic connections makes it possible to introduce reagents into the presynaptic terminals by diffusion from a cell body within a short time. Introduction of exogenous cDNA or siRNA performed by microinjection into a SCG neuron allows us to modulate the level of the protein of interest or to express mutant proteins in the neuron. Here, we describe use of the model SCG neuronal synapse to elucidate function of presynaptic proteins in mediating synaptic transmission. PMID- 17287043 TI - The physiology analysis system: an integrated approach for warehousing, management and analysis of time-series physiology data. AB - The physiology analysis system (PAS) was developed as a resource to support the efficient warehousing, management, and analysis of physiology data, particularly, continuous time-series data that may be extensive, of variable quality, and distributed across many files. The PAS incorporates time-series data collected by many types of data-acquisition devices, and it is designed to free users from data management burdens. This Web-based system allows both discrete (attribute) and time-series (ordered) data to be manipulated, visualized, and analyzed via a client's Web browser. All processes occur on a server, so that the client does not have to download data or any application programs, and the PAS is independent of the client's computer operating system. The PAS contains a library of functions, written in different computer languages that the client can add to and use to perform specific data operations. Functions from the library are sequentially inserted into a function chain-based logical structure to construct sophisticated data operators from simple function building blocks, affording ad hoc query and analysis of time-series data. These features support advanced mining of physiology data. PMID- 17287044 TI - Extrinsic mortality and the evolution of senescence. PMID- 17287045 TI - Palaeobiology: the origin and evolution of a scientific discipline. PMID- 17287046 TI - Verification of the "first flush" phenomenon in mine water from coal mines in the Upper Silesian Coal Basin, Poland. AB - Case studies of Grodziec and Siersza mines in the Upper Silesian Coal Basin confirm that mine water accumulating in and over-flowing from abandoned coal mines is subject to a "first flush" phenomenon. The accumulated products of sulphide oxidation are dissolved in the rising mine water and flushed out at concentrations several times those observed during mine operation. Following the first overflow, sulphate concentration and hydrogen ion activity decay exponentially. In the case of workings in Siersza, decay constants of -0.003 to 0.005 day(-1) are observed, corresponding to flushing times of 480 to 820 days, some 10-20 times the period required for the workings to flood. Quantities of leachable sulphur in the abandoned workings of 0.02-0.03% are adequate to explain the observed concentrations of sulphate in the first flush, and this figure is tentatively supported by laboratory analyses. PMID- 17287047 TI - A sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro apoptogenic. AB - Targeting chemotherapeutic agents directly to sites of DNA replication and repair within cancerous cells is problematic. This study attempts to address the issue of nuclear delivery of biologically active peptides with the potential to disrupt cancer cell growth. Herein, the protein transduction domain of the HIV-1 transactivator of transcription, Tat (Tat(48-60)), is used to deliver a cytotoxic peptide mimic of the cyclin-dependent kinase inhibitor, p21(WAF1/CIP1) into the nucleus. This construct, which we designate as Tat(48-60)-P10, contains the PCNA interacting protein (PIP) box. We demonstrate the utility of Tat(48-60) for peptide delivery to the nucleus and show that Tat(48-60)-P10 induces apoptosis specific to the inclusion of the wild type PIP box containing sequence. Colocalization of Tat(48-60)-P10 with nuclear PCNA was observed by immunofluorescence analysis, supporting the hypothesis that cytotoxicity is potentially related to disruption of nuclear PCNA function. The U251 and U373 glioma cell lines exhibited particular sensitivity to the construct. PMID- 17287048 TI - Prevenar vaccination: review of the global data, 2006. AB - The 7-valent pneumococcal conjugate vaccine, Prevenar, was first licensed in the United States in 2000 for the prevention of invasive pneumococcal disease (IPD) caused by the serotypes included in the vaccine. It is presently approved in more than 70 countries, and more than 100 million doses of vaccine have been distributed to date. Within 1 year of routine use in the US, incidence of vaccine serotype IPD had fallen dramatically among children younger than 2 years, with indirect effects noted among other age groups as well. The most recent data available from the US demonstrates that vaccine-serotype IPD has declined by 94% among the age group recommended for vaccination, and indirect effects have been documented in every unvaccinated age group, including among neonates and young infants. Additionally, declines in other pneumococcal-associated respiratory tract diseases have been reported, highlighting the extended benefits of a Prevenar vaccination program. Subsequently, the vaccine has been introduced into the national immunization programs of several other countries, including Canada, Australia, and The Netherlands. While an increase in disease caused by serotypes not included in the vaccine has been observed ("replacement disease"), the overall impact of this increase has, to date, been small in comparison to the substantial reduction in overall disease burden that has resulted since Prevenar introduction. PMID- 17287049 TI - ADP-ribosylation activity in pertussis vaccines and its relationship to the in vivo histamine-sensitisation test. AB - Pertussis toxin (PTx) is a major virulence factor produced by Bordetella pertussis. In its detoxified form (PTd), it is an important component of acellular pertussis vaccines although some residual PTx activity may likely be present because of the limitations of the detoxification processes used. Furthermore, different detoxification procedures have been shown to result in different amino acid side-chain modifications for the resulting PTd. The histamine-sensitisation test (HIST) in mice is currently used for the safety testing of these vaccines. However, an alternative test is needed because of large assay variability and ethical concerns. The ADP-ribosylation enzyme activity of PTx is thought to be the major factor responsible for the histamine sensitising activity detected in vivo. In the present study, the ADP-ribosylation activity in different acellular pertussis-based combination vaccine formulations was measured and compared with reactivity in the HIST. The results indicated that different products showed differences in ADP-ribosylation activity and a level which would be significant in relation to the reactivity seen in the HIST could not be defined, except for vaccines that contain genetically detoxified PTx, which do not have enzymatic activity nor in vivo toxicity. Different detoxification procedures as well as formulation factors could contribute to this variation. Relying solely on the residual enzyme activity of PTx in vaccines containing chemically detoxified PTd may not fully reflect the in vivo reactivity observed by the HIST. Refinement of the in vitro test to include a step which monitors the B-subunit activity of PTx may provide a better correlation with the in vivo HIST. PMID- 17287050 TI - Intragastric immunization with recombinant Lactobacillus casei expressing flagellar antigen confers antibody-independent protective immunity against Salmonella enterica serovar Enteritidis. AB - A recombinant Lactobacillus casei expressing a flagellar antigen from Salmonella enterica serovar Enteritidis was constructed and evaluated as a mucosal vaccine. Intragastric immunization of the recombinant strain conferred protective immunity against Salmonella infection in mice. This immunization did not result in antigen specific antibody in either feces or sera but induced the release of IFN-gamma on restimulation of primed lymphocytes ex vivo. The results suggested that the protective efficacy provided by flagellin-expressing L. casei is mainly attributable to cell-mediated immune responses. In addition, an adjuvant-type effect of the antigen delivery system with L. casei was also observed. PMID- 17287051 TI - Monitoring of ELISA-reactive antibodies against anthrax protective antigen (PA), lethal factor (LF), and toxin-neutralising antibodies in serum of individuals vaccinated against anthrax with the PA-based UK anthrax vaccine. AB - The human anthrax vaccines currently licensed contain the protective antigen (PA) of Bacillus anthracis as main antigen together with traces of some other bacillus components, e.g. lethal factor (LF). The present study aimed at monitoring the course of specific antibody titres against PA and LF by enzyme linked immunosorbent assays (ELISA), as well as the levels of toxin-neutralising antibodies, in 11 volunteers vaccinated with the human anthrax vaccine UK. After an initial seroconversion in all vaccinees, a significant reduction of both antibody titres against PA and LF, and of neutralising antibodies, was detected just prior to a vaccine boost 6 months after completion of the basic immunisation. Following the booster injection, titres increased again to levels comparable to those after the fourth immunisation. ELISA titres against PA correlated significantly with neutralising antibodies (r=0.816, p<0.001). Therefore, the less work- and time-consuming ELISA should be favoured to monitor the efficacy of an anthrax vaccination. PMID- 17287052 TI - Site-specific UBITh amyloid-beta vaccine for immunotherapy of Alzheimer's disease. AB - The UBITh AD immunotherapeutic vaccine for Alzheimer's disease uses an amyloid beta (Abeta) immunogen having two designer peptides that have been engineered to elicit anti-N terminal Abeta(1-14) antibodies while minimizing potential for the generation of adverse anti-Abeta immune responses. The vaccine has been further designed for minimization of inflammatory reactivities through the use of a proprietary vaccine delivery system that biases Th2 type regulatory T cell responses in preference to Th1 pro-inflammatory T cell responses. In vitro studies and in vivo studies in small animals, baboons and macaques show that anti Abeta antibodies are generated with the expected N-terminus site-specificity, and that these antibodies have functional immunogenicities to neutralize the toxic activity of Abeta and promote clearance of plaque deposition. The antibodies appear to draw Abeta from the CNS into peripheral circulation. Results indicate that the UBITh AD vaccine did not evoke anti-Abeta cellular responses in a transgenic mouse model for AD. The vaccine was safe and well tolerated in adult Cynomolgus macaques during a repeat dose acute and chronic toxicity study. PMID- 17287053 TI - Safety review: two outer membrane vesicle (OMV) vaccines against systemic Neisseria meningitidis serogroup B disease. AB - MenBvac is an OMV vaccine against systemic serogroup B Neisseria meningitidis disease. MenBvac was developed for control of a B:15:P1.7,16 subtype epidemic in Norway and administered to 180,000 subjects in 28 clinical studies. MeNZB, a daughter vaccine of MenBvac, was developed for a clonal B:4:P1.7b,4 epidemic in New Zealand and administered to 1 million people <20 years. The vaccines were similar regarding reactogenicity profile. Serious adverse events (SAEs) in general and particularly neurologic SAEs were very rare. Despite frequently reported local reactions and fever in those under 5 years, these OMV-based vaccines containing 25 microg antigen can be considered safe for use in all age groups. PMID- 17287054 TI - Active immunization against Alzheimer's beta-amyloid peptide using phage display technology. AB - Beta-amyloid peptide (AbetaP) aggregation, an essentially early event in Alzheimer's disease (AD) pathogenesis, became a target for therapeutics. We developed an immunization procedure, using as antigen the EFRH peptide located at the N-terminal region of AbetaP displayed on the filamentous phage, to raise anti beta-amyloid peptide antibodies. Data demonstrated that a bacteriophage displaying different numbers of copies of self-epitope modulates the intensity of the immuno response. This immunization procedure led to improvement in cognitive functions and alleviated amyloid pathology in a transgenic mouse (Tg) model of AD. PMID- 17287055 TI - A plant-produced plague vaccine candidate confers protection to monkeys. AB - Production of vaccine antigens in plants has received considerable attention over the last decade. However, despite many antigens being expressed in plant systems, and promising efficacy data with rodent models, few vaccine candidates have advanced into studies in non-human primates or human clinical trials. Here, we report on the transient expression of the F1 and LcrV antigens of Yersinia pestis in Nicotiana benthamiana. The antigens were expressed as fusions to the thermostable enzyme of Clostridium thermocellum. When administered to Cynomolgus Macaques the purified plant-produced antigens induced serum IgG and IgA responses specific to F1 and LcrV, and conferred complete protection against lethal challenge with Y. pestis. This study clearly demonstrates the efficacy of a plant produced plague vaccine candidate in a primate model. PMID- 17287056 TI - DNA vaccines expressing glycoprotein complex II antigens gM and gN elicited neutralizing antibodies against multiple human cytomegalovirus (HCMV) isolates. AB - Human cytomegalovirus (HCMV) glycoprotein complex II (gcII) consists of two glycoproteins, gM and gN. Although gcII specific IgG purified from HCMV positive patient sera can neutralize HCMV, there has been no report describing the generation of virus-neutralizing antibodies by immunization with individual recombinant gM or gN antigens. In the current study, gM and gN antigens were expressed by the mammalian expression vector pJW4303 and used as DNA vaccines to determine the immunogenicity of these proteins. Sera from mice or rabbits immunized with individual or combinations of gM and gN DNA vaccines contained gM and gN specific antibodies as confirmed by ELISA and Western blot analyses. The combined gM and gN antigens induced the strongest antibody responses that recognized both gM and gcII complex while gM DNA vaccine alone could only elicit antibody specific for gM antigen. When given alone, the gN DNA vaccine did not induce detectable gcII specific antibody even though in vitro gN expression was confirmed by the formation of gM/gN complex in FSK cells using a gN-specific monoclonal antibody 14-16A. The neutralizing antibody titer of anti-gM/gN sera (1:128) was higher than that of anti-gM sera (1:32) against the autologous virus, HCMV AD169. Heterologous HCMV strains including Towne and Davis could also be neutralized by the anti-gM/gN antisera. Our data supported the rationale for the use of the HCMV gM/gN protein complex as protective antigens for subunit based HCMV vaccine development. DNA vaccination is an effective approach to express the gM/gN antigen complex in vivo without the need to express and purify these highly insoluble and structurally complicated antigens. PMID- 17287057 TI - Histological examination of drill sites in bovine rib bone after grinding in vitro with eight different devices. AB - The way in which bone is processed may affect the quality of the specimen and how much information may be gleaned on histological examination. We investigated eight widely used rasps and drills and compared the results. All large chip cutters damaged the bed and marrow of the bone. The tool that caused the least damage was the wet grinding diamond tool. PMID- 17287058 TI - Clinical results of dermofasciectomy for Dupuytren's disease in Japanese patients. AB - The surgical outcomes of dermofasciectomy for Dupuytren's disease were evaluated in nine hands of eight patients in a Japanese population. The patients were examined for postoperative complications, problems associated with the skin graft, evidence of recurrent disease, sensation over the graft and pre- and postoperative range of motion at the metacarpophalangeal and the proximal interphalangeal joints. The mean two-point discrimination over the skin graft was 14 mm. The mean remaining flexion contracture at the metacarpophalangeal joint was 5 degrees and that at the proximal interphalangeal joint was 34 degrees . Recurrence occurred in two patients: one had a minor nodule and the other a natatory cord, which did not result in the redevelopment of a contracture. This study supports the use of dermofasciectomy for the treatment of recurrent Dupuytren's disease, as well as for the treatment of primary disease in those patients with a strong Dupuytren's diathesis in this population. PMID- 17287059 TI - Material and social deprivation and health and social services utilisation in Quebec: a local-scale evaluation system. AB - Very few studies have employed local-scale analyses to evaluate how well primary health care and social services reach the most socially and economically deprived individuals. This paper describes a project, conducted in close partnership with decision-makers and practitioners at selected local community service centres (in French, CLSCs) in Quebec, Canada, that developed a system for assessing primary care and social services utilisation by applying deprivation levels defined at the local scale (i.e., according to the distribution of deprivation in individual CLSC service areas). More than 25 years ago, Quebec started setting up a province wide network of publicly financed CLSCs whose mission was to offer first-line health and social services at the local level. Now approximately one Quebecer in four receives at least one service a year from a CLSC. The evaluation system presented in this article is built on deprivation profiles for each CLSC service area and comprises maps, relative indices of service utilisation, and an interpretation framework that facilitates the integration of new data into the decision-making and services planning processes. Study results show that deprivation levels, when defined using local perspectives, correspond more closely to decision-makers' perceptions, that relative indices are sensitive to key determinants of services provision and utilisation, and that the interpretation framework is useful for reassessing intervention strategies. PMID- 17287060 TI - Dibenzanthracenes and benzochrysenes elicit both genotoxic and nongenotoxic events in rat liver 'stem-like' cells. AB - Polycyclic aromatic hydrocarbons (PAHs) with molecular weight 278 are a group of PAHs that are mostly not covered by the current monitoring programs, despite their relative abundance in environmental samples and possible carcinogenicity. Although benzo[g]chrysene (BgChry) and dibenz[a,h]anthracene (DBahA) have been for a long time studied as genotoxic, tumour-initiating compounds, little is known about the potential tumour-promoting effects of this group of PAHs. In the present study, we investigated their impact on activation of the aryl hydrocarbon receptor (AhR), induction of enzymes involved in metabolic activation of PAHs, disruption of cell cycle control in confluent cell population and inhibition of gap junctional intercellular communication (GJIC), using the rat liver epithelial cell line WB-F344 as a model of liver progenitor cells. We found that BgChry was the weakest inducer of the AhR-mediated activity, while relative potencies of benzo[b]chrysene (BbChry) and benzo[c]chrysene (BcChry) were comparable to the previously reported values for dibenzanthracenes. All compounds increased expression of cytochromes P450 1A1 and 1B1, and aldo-keto reductase 1C9. BgChry was found to induce high amounts of DNA adducts, which corresponded with induction of p53 phosphorylation at Ser15, apoptosis and accumulation of cells in S-phase of cell cycle, leading to a decrease in cell numbers. All other compounds were found to stimulate cell proliferation in contact-inhibited WB-F344 cells in a dose-dependent manner. We found that only BgChry, and to a lesser extent also BcChry, inhibited GJIC at high concentrations. Taken together, dibenzanthracenes and benzochrysenes, with exception of BgChry, seem to act primarily through deregulation of cell proliferation in liver epithelial cells, which is related to their relatively high AhR-mediated activity. The disruption of cell cycle control might contribute to their carcinogenic effects, as well as to carcinogenicity of complex environmental mixtures containing high levels of PAHs with molecular weight 278. PMID- 17287061 TI - Death in correctional facilities: opportunities for automated external defibrillation. AB - BACKGROUND: Death due to cardiovascular disease occurs more frequently in prisons than the national average. Due to close surveillance 24 h/day, the ability to reach the patient within 3 min and time consuming access for the EMS crews, it was hypothesised that the deployment of automated external defibrillators (AEDs) might make improvements regarding Call-to-the-First-AED-Prompt (CTP) interval and formed the aim of this study. METHODS: Our investigation was analysed on an intention to treat basis and conducted in a prospective, open and observational design. As the primary outcome, the CTP-intervals were compared to the arrival intervals of the EMS. As a secondary outcome, an analysis of all deceased inmates was described. RESULTS: The average daily population of inmates in Austrian correctional facilities is 7714. During a period of 13 months, 10 instances in which an AED was activated and electrodes attached to a collapsed inmate, were reported. The CTP-interval (median+/-S.D.) was 2.3+/-1.6 S.D. min. It took the EMS 10.0+/-4.3 S.D. min. to arrive at the patient's side. Four out of 10 cases of cardiac arrest occurred due to myocardial infarction. Of 39 deceased inmates, a post mortem examination was completed in 34 cases. In 13 cases, cardiovascular disease was the cause of death. DISCUSSION: The main finding was a four-fold reduction of the CTP-interval. This fact indicates the potential improvements which could be achieved with the deployment of AEDs. Our secondary objective revealed that death due to cardiovascular disease was found in a high proportion and could be considered to be a strong incentive to initiate programmes to counter cardiovascular death in prison. PMID- 17287062 TI - Comparison of ventilation and cardiac compressions using the Impact Model 730 automatic transport ventilator compared to a conventional bag valve with a facemask in a model of adult cardiopulmonary arrest. AB - PURPOSE: To determine the performance of two person CPR on an instrumented manikin by registered nurses using conventional bag valve mask (BVM) ventilation or the Impact Model 730 automatic transport ventilator (Impact 730, Impact Instrumentation, Inc., West Caldwell, NJ) in CPR mode using a face mask. DESIGN: Randomized crossover quasi-experimental. SETTING: Laboratory simulation. SUBJECTS: Twenty-eight registered nurses trained in performing adult cardiopulmonary resuscitation (CPR). INTERVENTIONS: Basic Life Support was provided by subjects using a conventional bag valve mask (BVM) ventilation or mask ventilation with an automatic transport ventilator, the Impact 730, which incorporates a metronome to facilitate chest compression timing. Subjects alternated performing 4min of CPR using the BVM or Impact 730 to deliver breaths with a mask while the other subject performed compressions. MEASUREMENTS AND MAIN RESULTS: Flow, volume and pressure were measured using a pneumotachograph and pressure transducer, and ease of use was measured using a 10cm visual analogue scale. There was no statistical or clinical difference between the actual and recommended tidal lung volume (mean+/-S.D.) delivered by the Impact 730 (-120.4+/ 91.5ml) versus the BVM (-119.8+/-187.3+/-ml). Ventilation with the BVM resulted in more (137.7+/-143.9ml) air per breath passing through the simulated lower esophageal sphincter compared to the Impact 730 (14.0+/-16.8ml, p<0.05). The reduced mask leak per breath with the Impact 730 (176.1+/-98.3ml) compared to the BVM (367.6+/-337.7ml, p<0.05) is likely to have resulted from the subject being able to manage the mask with two rather than one hand and is reflected in the higher ease of use score on a 10cm visual analogue scale with the Impact 730 (8.06+/-1.35cm) versus the BVM (6.46+/-2.46cm, p<0.05). Subjects tended to deliver slightly more compressions and breaths when using the BVM. CONCLUSION: Compared to the BVM, the Impact 730 is as effective, easier to use and limits the amount of gas entering the stomach when used during adult CPR in a simulated setting. PMID- 17287063 TI - Prediction of countershock success using single features from multiple ventricular fibrillation frequency bands and feature combinations using neural networks. AB - Targeted defibrillation therapy is needed to optimise survival chances of ventricular fibrillation (VF) patients, but at present VF analysis strategies to optimise defibrillation timing have insufficient predictive power. From 197 patients with in-hospital and out-of-hospital cardiac arrest, 770 electrocardiogram (ECG) recordings of countershock attempts were analysed. Preshock VF ECG features in the time and frequency domain were tested retrospectively for outcome prediction. Using band pass filters, the ECG spectrum was split into various frequency bands of 2-26 Hz bandwidth in the range of 0-26 Hz. Neural networks were used for single feature combinations to optimise prediction of countershock success. Areas under curves (AUC) of receiver operating characteristics (ROC) were used to estimate prediction power of single and combined features. The highest ROC AUC of 0.863 was reached by the median slope in the interval 10-22 Hz resulting in a sensitivity of 95% and a specificity of 50%. The best specificity of 55% at the 95% sensitivity level was reached by power spectrum analysis (PSA) in the 6-26 Hz interval. Neural networks combining single predictive features were unable to increase outcome prediction. Using frequency band segmentation of human VF ECG, several single predictive features with high ROC AUC>0.840 were identified. Combining these single predictive features using neural networks did not further improve outcome prediction in human VF data. This may indicate that various simple VF features, such as median slope already reach the maximum prediction power extractable from VF ECG. PMID- 17287064 TI - Introduction of a treatment algorithm can improve the early management of emergency patients in the resuscitation room. AB - INTRODUCTION: Successful management of emergency patients with multiple trauma in the hospital resuscitation room depends on the immediate diagnosis and rapid treatment of the most life-threatening injuries. In order to reduce the time spent in the resuscitation room, an in-hospital algorithm was developed in an interdisciplinary team approach with respect to local structures. The aim of the study was to analyse whether this algorithm affects the interval between hospital admission and the completion of diagnostic procedures and the start of life saving interventions. Moreover, in-hospital mortality was investigated before and after the algorithm was introduced. MATERIAL AND METHODS: In this prospective study, all consecutive trauma patients in the resuscitation room were investigated before (group I, 01/04-10/04) and after (group II, 01/05-11/05) introduction of the algorithm. The times between hospital admission and the end of the diagnostic procedures (ultrasound [sono], chest X-ray [CF], and cranial computed tomography [CCT]), and between hospital admission and the start of life saving interventions were registered and in-hospital mortality analysed. RESULTS: In the study period, 170 patients in group I and 199 patients in group II were investigated. Injury severity score (ISS) were comparable between the two groups. The intervals between admission and completion of diagnostic procedures were significantly lower after the algorithm was introduced (mean+/-S.D.): sono (11 +/ 10 min versus 7 +/- 6 min, p < 0.05), CF (21 +/- 12 min versus 12 +/- 9 min, p < 0.01), and CCT (55 +/- 27 min versus 32 +/- 14 min, p < 0.01). Moreover, the interval to the start of life-saving interventions was significantly shorter (126 +/- 90 min versus 51 +/- 20 min, p < 0.01). After introducing the algorithm, in hospital mortality was reduced significantly from 33.3% to 16.7% (p < 0.05) in the most severely injured patients (ISS>or=25). CONCLUSION: The introduction of an algorithm for early management of emergency patients significantly reduced the time spent in the resuscitation room. The periods to completion of sono, CF, and CCT, respectively, and the start of life-saving interventions were significantly shorter after introduction of the algorithm. Moreover, introduction of the algorithm reduced mortality in the most severely injured patients. Although further investigations are needed to evaluate the effects of the Heidelberg treatment algorithm in terms of outcome and mortality, the time reduction in the resuscitation room seems to be beneficial. PMID- 17287065 TI - Customized birthweight standards for a Spanish population. AB - OBJECTIVE: To analyse the biological factors affecting birthweight and to derive customized birthweight standards for a Spanish population. METHODS: A retrospective cohort was created with all the singleton pregnancies delivered at term and free of pathology in our Institution. Birthweight was modeled by multiple linear regression from maternal (ethnic origin, maternal height, booking weight, smoking, and parity), and fetal (gender, gestational age) characteristics. RESULTS: In addition to gestational age and sex, height, booking weight, ethnic origin, parity, and smoking all have significant and independent effects on birthweight. Women from East-Asia, Morocco and South-America had newborns on average 83 g, 74 g and 95 g heavier than White-European Spanish women. The effect of smoking was found to be dose-related. CONCLUSION: We found the relative effect of the maternal and fetal characteristics to be very similar to that reported in previous studies. We report coefficients for ethnic groups that account for a sizeable proportion of the population composition of several European countries. PMID- 17287066 TI - Alterations of estrogen receptor-alpha and -beta in the anterior vaginal wall of women with urinary incontinence. AB - OBJECTIVES: The objective was to investigate the alterations in estrogen receptor alpha and -beta (ER-alpha and ER-beta) in the anterior vaginal wall of women with stress urinary incontinence (SUI). STUDY DESIGN: Samples of the anterior vaginal wall were taken from 57 women, including 12 women with premenopausal SUI (pre-M SUI), 12 with premenopausal control (pre-M control), 19 with postmenopausal SUI (post-M SUI), and 14 with postmenopausal control (post-M control). The expressions of ER-alpha and ER-beta were assayed by immunohistochemistry and quantified with the H-score method. RESULTS: Serum estradiol was significantly lower in the pre-M SUI than in the pre-M control group (P<0.01), but the difference between the post-M SUI and post-M control groups was not significant (P>0.05). ER-alpha in endothelia, smooth muscle cells, and fibrocytes were significantly lower in pre-M SUI than in pre-M control (P<0.01), but there were no significant differences of ER-alpha between the post-M SUI and post-M control groups (P>0.05). ER-beta in endothelia and fibrocytes were significantly lower in the pre-M SUI than in the pre-M control group (P<0.01), and ER-beta in fibrocytes was significantly lower in the post-M SUI than in the post-M control group (P<0.01). CONCLUSIONS: Alterations in serum estradiol and its receptors (ER-alpha and ER-beta) in the anterior vaginal wall were demonstrated, suggesting their involvement in the occurrence of female SUI. PMID- 17287067 TI - Interleukin-13 stimulates the secretion of vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 by human oviductal epithelial cells. AB - OBJECTIVE: The aim of this study is to evaluate the effects of interleukin (IL) 13, a Th2 cytokine, on the production of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in human oviductal cells in vitro. STUDY DESIGN: Human oviductal epithelial cells (OECs) were isolated from five premenopausal patients. The secretion of VEGF(165) and sFlt-1 by cultured OECs in response to IL-13 was measured using an enzyme-linked immunosorbent assay. RESULTS: The secretion of VEGF(165) and sFlt-1 was detected in cultured OECs under untreated conditions. IL-13 enhanced the secretion of VEGF(165) and sFlt-1 by OECs in a dose-dependent manner. CONCLUSION: The present findings suggest that IL-13 is a regulatory factor of VEGF and sFlt-1 production in the human fallopian tubes. IL-13 in the local environment may stimulate oviductal vascular permeability by inducing the production of VEGF by oviductal cells. The modulation of VEGF secretion by IL-13 secreted by the peri implantation embryo may contribute to the normal and pathological processes of human reproduction during the peri-implantation period. PMID- 17287068 TI - Assessment of spatial-temporal patterns of surface and ground water qualities and factors influencing management strategy of groundwater system in an urban river corridor of Nepal. AB - This study examined the spatial-temporal variations and factors influencing the management of groundwater along a section of the Bagmati river corridor in the Kathmandu valley (Nepal). The results showed that rural areas were less polluted than urban areas. In urban areas, the biochemical oxygen demand (BOD), total nitrogen (TN) and total phosphorus (TP) concentrations ranged from 8.41 to 29.74 mg/L, 6.7 to 128.96 mg/L and 0.06 to 1.5 mg/L, respectively. In rural areas, the BOD, TN and TP concentrations ranged from 0.78 to 18.25 mg/L, 4.8 to 11.56 mg/L and 0.07 to 0.65 mg/L, respectively. The level of organics was higher in the pre monsoon season, while the level of nutrients was higher in post-monsoon season. A comparison of the groundwater and surface water in the upstream rural areas revealed that the TP concentration was higher in the groundwater than in the surface water, which was attributed to the sorption of phosphorus on iron, aluminum or calcium compounds contained in the surface water, which depends upon the temperature, pH and dissolved oxygen. In urban areas, a few wells were found at groundwater levels lower than the corresponding surface water levels and were subjected to a high risk of pollution. Overall, these findings reinforce the notion that the management of surface and ground waters in an integrated approach is essential for attaining sustainable development of groundwater systems. PMID- 17287069 TI - Environmental regulatory failure and metal contamination at the Giap Lai pyrite mine, Northern Vietnam. AB - The causes for the failure in enforcement of environmental regulations at the Giap Lai pyrite mine in northern Vietnam are considered and the environmental impacts that are associated with this mine are evaluated. It is shown that sulphide-rich tailings and waste rock in the mining area represent significant sources of acid rock drainage (ARD). The ARD is causing elevated metal levels in downstream water bodies, which in turn, represent a threat to both human health and to aquatic ecosystems. Metal concentrations in impacted surface waters have increased after mine closure, suggesting that impacts are becoming progressively more serious. No post-closure, remediation measures have been applied at the mine, in spite of the existence of environmental legislation and both central and regional institutions charged with environmental supervision and control. The research presented here provides further emphasis for the recommendation that, while government institutions may need to be strengthened, and environmental regulations need to be in place, true on the ground improvement in environmental quality in Vietnam and in many other developing countries require an increased focus on promoting public awareness of industrial environmental issues. PMID- 17287070 TI - Environmental restoration of invaded ecosystems: how much versus how often? AB - This paper derives the optimal level of restorative efforts required to restore environments degraded by invasive species invasion. Specific attention is focused on a case when restoration faces the risk of failure through relapse of the restored environment caused by repeat invasions. The level of restored environment may also play a role in its future improvement or susceptibility to failure. The tradeoff between the optimal level of environmental quality and number of restorative efforts required to attain that given environmental quality is highlighted. PMID- 17287071 TI - Removal of o-nitrophenol from water by electrochemical degradation using a lead oxide/titanium modified electrode. AB - This study examined o-nitrophenol removal from aqueous solutions by electrochemical oxidation employing a modified electrode. The modified electrode was produced by electrodepositing lead oxide onto a titanium substrate. Following electrochemical oxidation of o-nitrophenol-containing solutions, the remaining o nitrophenol concentration and chemical oxygen demand (COD) values were determined. The optimum parameters were current density of 40 mA cm(-2), pH of 2.47, 60 min of electrolysis time, 4 g L(-1) NaCl electrolyte solution and temperature of 30 degrees C. Under these optimum conditions of electrochemical degradation using a lead oxide/titanium modified electrode complete removal of o nitrophenol and COD was achieved. PMID- 17287072 TI - Editorial Comment on: Associations of single nucleotide polymorphisms in the vascular endothelial growth factor gene with the characteristics and prognosis of renal cell carcinomas. PMID- 17287074 TI - Nephron-sparing surgery in renal cell carcinoma: did we sacrifice too many kidneys in the past? PMID- 17287075 TI - Determination of the fraction of active inputs required by a neuron to fire. AB - What fraction of the inputs to a neuron in the primary visual cortex (V1) need to be active for that neuron to reach its firing threshold? The paper describes a numerical method for estimating the selectivity of visual neurons, in terms of the required fraction of active excitatory inputs, from standard data produced by intracellular electro-physiological recordings. The method also provides an estimate of the relative strength of the feedforward inhibition in a push-pull model of the inputs to V1 simple cells. The method is tested on two V1 cells described in Carandini and Ferster [Carandini, M., Ferster, D., 2000. Membrane potential and firing rate in cat primary visual cortex. J. Neurosci. 20, 470 484]. The results indicate that the maximum strength of feedforward inhibition is around 30% of the maximum strength of feedforward excitation. The two V1 neurons investigated fire if more than around 40% of their excitatory LGN inputs are active. PMID- 17287073 TI - Associations of single nucleotide polymorphisms in the vascular endothelial growth factor gene with the characteristics and prognosis of renal cell carcinomas. AB - OBJECTIVES: Vascular endothelial growth factor (VEGF) is considered to play critical roles in tumor development and progression, especially in renal cell carcinoma (RCC) via von Hippel-Lindau gene inactivation. Although VEGF -2578CC, 1154GG, and -634CC genotypes are reportedly correlated with higher levels of VEGF production, no previous studies have reported on the associations of these polymorphisms with RCCs. This study was aimed to clarify the effects of these functional polymorphisms on RCC progression and prognosis. METHODS: We investigated the associations of three polymorphisms (-2578C/A, -1154G/A, and 634C/G) in the VEGF gene with the clinicopathologic parameters and survival of 213 patients with RCC. The -2578C/A and -634C/G polymorphisms were genotyped using a polymerase chain reaction (PCR) restriction fragment length polymorphism technique and the -1154G/A polymorphism was genotyped by an amplification refractory mutation system PCR technique. RESULTS: The GA+AA genotypes of 1154G/A were weakly associated with smaller tumors, lower tumor stage, and lower stage grouping (p=0.028, p=0.012, and p=0.028, respectively). The CA and CA+AA genotypes of -2578C/A were weakly associated with less frequent lymph node metastasis (p=0.029 and p=0.034, respectively) and were significantly associated with favorable cancer-specific survival (p=0.047 and p=0.048, respectively). There was no apparent clinical effect of the -634C/G polymorphism. CONCLUSIONS: These results suggest that some VEGF genotypes may have effects on RCC progression or prognosis, possibly through altered VEGF expression. This finding might help in clarifying the mechanisms of RCC development and progression. PMID- 17287076 TI - Ion channel density and threshold dynamics of repetitive firing in a cortical neuron model. AB - Modifying the density and distribution of ion channels in a neuron (by natural up and down-regulation, by pharmacological intervention or by spontaneous mutations) changes its activity pattern. In the present investigation, we analyze how the impulse patterns are regulated by the density of voltage-gated channels in a model neuron, based on voltage clamp measurements of hippocampal interneurons. At least three distinct oscillatory patterns, associated with three distinct regions in the Na-K channel density plane, were found. A stability analysis showed that the different regions are characterized by saddle-node, double-orbit, and Hopf bifurcation threshold dynamics, respectively. Single strongly graded action potentials occur in an area outside the oscillatory regions, but less graded action potentials occur together with repetitive firing over a considerable range of channel densities. The presently found relationship between channel densities and oscillatory behavior may be relevance for understanding principal spiking patterns of cortical neurons (regular firing and fast spiking). It may also be of relevance for understanding the action of pharmacological compounds on brain oscillatory activity. PMID- 17287077 TI - Application and interpretation of FISH in biomarker studies. AB - Emerging genomic and proteomic data is creating new opportunities to identify novel biomarkers that will have pathway-specific therapeutic impact on cancer progression. Molecular cytogenetic and fluorescence in situ hybridization (FISH) methods have been primarily used in discovery genetic research laboratories until recently. New automated analytical platforms based on FISH technologies and tissue microarray methods are providing a rapid means to determine the impact of consistent genomic aberrations in clinical trials, and in studies designed to investigate differential chemotherapeutic response. PMID- 17287078 TI - Synthesis of photocatalytic TiO2 thin films via the high-pressure crystallization process at low temperatures. AB - TiO2 thin films with a monophasic anatase structure were synthesized via a high pressure crystallization (HPC) process which successfully lowered the crystallization temperature of TiO2 films from 350 to 150 degrees C. The thermal budget and energy consumption during the crystallization process were markedly reduced and dense films without cracks were obtained. During the HPC process, crystallization took place throughout the films and TiO2 films with uniform crystallinity were obtained. The HPC process also led to an enhancement in the wettability of TiO2 thin films. The hydrophilicity of the films increased with heating temperatures via high-pressure annealing. In comparison with the conventional annealing, the HPC process not only produced TiO2 films with superior photo-induced super-hydrophilicity, but also led to higher photocatalytic activity of the films. The HPC process was confirmed to provide a new route for synthesizing well-crystallized anatase TiO2 thin films with high photocatalytic activity and good wettability at low temperatures. PMID- 17287079 TI - Chemical and physicochemical profile of wastewaters produced from the different stages of Spanish-style green olives processing. AB - The main purpose of the processing of table olives is the removal, at least partially, of the natural bitterness of the fruit in order to render it edible. The preparation of Spanish-style green olives after harvesting involves cleaning followed by debittering using NaOH solution, washing with water, a lactic acid fermentation step and finally canning. Wastewaters originating from table olives processing industries pose an important environmental threat, as they are characterized by a very high organic load and high concentration of phenolic compounds, which are toxic to living organisms. In this communication, the chemical and physicochemical profile of wastewaters produced from the different stages of Spanish-Style green olives processing was investigated. Phenolic compounds, organic acids, amino acids and total sugars along with common physicochemical parameters were determined in order to appraise the specific features of each individually produced wastewater. PMID- 17287080 TI - Response of risperidone treatment may be associated with polymorphisms of HTT gene in Chinese schizophrenia patients. AB - Serotonin transporter (5-HTT) is a key component of the serotonergic neurotransmitter system. Few studies have focused on polymorphisms of the serotonin transporter and antipsychotic response and, in particular, there have so far been no published studies on the association between the serotonin transporter and response to risperidone. This study examined the relationship between two polymorphisms of the serotonin transporter and the efficacy of risperidone treatment in 129 patients with schizophrenia. Our results revealed that patients with l allele of HTTRLP showed a greater improvement than those without l allele on the overall brief psychiatric rating scale (BPRS) (P=0.025). But no such relationship was found for the HTTVNTR. In haplotype analysis, the frequency of L-12 haplotype showed a significant difference between the responder group and the non-responder group (P=0.005). Our study has, for the first time, produced evidence that the potential for therapy in patients with schizophrenia is related to the HTTRLP polymorphism in the HTT gene and haplotype L-12 may help to predict risperidone treatment efficiency. PMID- 17287081 TI - The colocalization of CGRP receptor and AMPA receptor in the spinal dorsal horn neuron of rat: a morphological and electrophysiological study. AB - Both the calcitonin gene-related peptide (CGRP) receptor and alpha-amino-3 hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor are involved in the transmission of sensory information from primary afferent to the spinal cord. The present study found that there was a colocalization of CGRP receptor and AMPA receptor in a single spinal dorsal horn neuron in rat determined by double immunofluorescence labeling image methods. Furthermore, our results showed that the evoked discharge frequency of the wide dynamic range (WDR) neuron, one type of the dorsal horn neurons, increased significantly after micro-iontophoretic delivery of CGRP or AMPA alone tested by extracellular recording, indicating a functional colocalization of CGRP receptor and AMPA receptor in a single spinal dorsal horn neuron. The results of the present study found a morphological and functional colocalization of the CGRP receptor and AMPA receptor in a single dorsal horn neuron that involved in the transmission and modulation of sensory information from primary afferent to the spinal cord in rats. PMID- 17287082 TI - Gene expression in the peripheral leukocytes and association analysis of PDLIM5 gene in schizophrenia. AB - PDLIM5 modulates neuronal calcium signaling, co-localizes with synaptic vesicles of neurotransmitters and positive association between its gene and schizophrenia was reported but its relation is still ambiguous. The differential expression of the PDLIM5 gene both in the brain and in the lymphoblasts has been found in schizophrenia compared to control subjects. In this study, we measured the expression level of the PDLIM5 gene transcripts in the peripheral leukocytes from 19 medication-free and 21 chronically medicated schizophrenic patients as well as age- and sex-matched control subjects using a quantitative real-time PCR method. The mRNA levels of the PDLIM5 gene in the leukocytes of medication-free schizophrenic patients were significantly higher than those of control subjects. On the other hand, our group has previously shown that its mRNA expression in the leukocytes of medication-free major depressive patients was significantly lower compared with controls. There was no difference in the PDLIM5 mRNA levels between chronic schizophrenic patients with antipsychotic medication and their controls. Further, we failed to find any genetic association between the PDLIM5 gene and schizophrenia with six single nucleotide polymorphics (SNPs) of the PDLIM5 gene in Japanese subjects (279 subjects each) and there was no significant relation between PDLIM5 gene and schizophrenia with the haplotype analysis (P=0.48), either. We suggest that the higher expression levels of the PDLIM5 mRNA in the peripheral leukocytes may be a candidate marker for medication-free schizophrenic patients. PMID- 17287083 TI - iNOS expression in rat aorta is increased after spinal cord transection: a possible cause of orthostatic hypotension in man. AB - Orthostatic hypotension commonly occurs in persons with spinal cord injury (SCI), limiting rehabilitation and independence. Findings of increased production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) after exposure to simulated microgravity suggest that increased iNOS expression contributes to OH in persons with SCI. To test this possibility, male Wistar rats underwent surgical transection of the spinal cord (T10) or sham-SCI surgery followed by euthanasia 3, 7 or 14 days later. Expression in thoracic aortic of inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) NOS was then determined. In SCI rats, expression of iNOS mRNA was decreased at 3 days, had returned to normal levels of expression at 7 days and was increased at 14 days post-SCI (1.8-fold). In contrast, levels of eNOS mRNA were increased at 3 days (1.4-fold), then declined over time reaching levels by day 14 that were reduced compared to sham SCI (0.23-fold). There were no significant effects of SCI on nNOS expression. These findings suggest a possible role for increased iNOS expression in the pathogenesis of OH in persons with SCI. PMID- 17287084 TI - The operand-order effect in single-digit multiplication: an ERP study of Chinese adults. AB - Unlike those used in the West, a typical Chinese multiplication table includes only smaller-operand-first entries (e.g., 3 x 7=21, but not 7 x 3=21). Due to this unique feature, multiplication for Chinese subjects has been found to show an operand-order effect. The present study aims to investigate the neural bases of the operand-order effect. Subjects were 20 Mainland Chinese subjects who learned as children the half multiplication table (i.e., smaller-operand-first entries only) and 20 Hong Kong and Macao Chinese subjects who learned as children the whole multiplication table (i.e., both smaller- and larger-operand-first entries) under the British and Portuguese educational systems, respectively. ERP data showed that, for those who learned the half table (Mainland Chinese), but not for those who learned the whole table (Hong Kong and Macao Chinese), the larger-operand-first problems elicited greater negative potentials across representative electrodes of the whole scalp, emerging at about 120 ms after the onset of the second operand and lasting until around 750 ms. These results suggest that the particular experience of acquiring multiplication facts had pronounced impact on their representations in the brain. PMID- 17287085 TI - Induction of IP-10 (CXCL10) in astrocytes following Japanese encephalitis. AB - Chemokines and their receptors are important elements for the selective attraction and activation of various subsets of leukocytes. Interferon-gamma inducible protein (IP-10 or CXCL-10) is a potent chemoattractant and has been suggested to enhance the severity of virus infection and neuronal injury. In order to assess functional importance of this chemokine in viral encephalitis, we have exploited an experimental model of Japanese encephalitis. We report for the first time that in Japanese encephalitis, astrocytes are the predominant source of IP-10. A progressive increase in IP-10 induction following viral infection is concomitant with the increase in IFN-gamma a known inducer of IP-10. However, this increase in IFN-gamma level is not sufficient to confer protection as animals eventually succumb to the infection. PMID- 17287086 TI - Prevalence of Cryptosporidium species and genotypes in mature dairy cattle on farms in eastern United States compared with younger cattle from the same locations. AB - Feces collected from 541 milking cows on two dairy farms each in Vermont, New York, Pennsylvania, Maryland, Virginia, North Carolina, and Florida were examined for the presence of Cryptosporidium oocysts. Oocysts were concentrated from 15 g of feces from each cow and DNA was extracted. A two-step nested PCR protocol was used to amplify an 830 base pair fragment of the SSUrRNA gene. PCR-positive products were purified and sequenced. PCR-positive findings were obtained from cows in all seven states and from 11 of 14 farms. Cryptosporidium parvum, Cryptosporidium bovis, and Cryptosporidium andersoni were found on 2, 6, and 8 farms, and infected 0.4, 1.7, and 3.7% of the 541 cows, respectively. The overall lower prevalence of Cryptosporidium in these cows was very highly significant (p< or =0.0001) compared with younger cattle and the relative prevalence of each species of Cryptosporidium also differed when compared with younger cattle previously examined on most of these same farms. The very low level of infection with C. parvum, the major species pathogenic to both cattle and humans, suggests that mature dairy cattle are a relatively low risk source of infection for humans. PMID- 17287087 TI - Rationale and clinical application of alkylphospholipid analogues in combination with radiotherapy. AB - Concurrent treatment with radiotherapy and chemotherapy has emerged as an effective strategy to improve clinical outcome of cancer. In addition to combining radiation with classical anticancer agents, several new biological response modifiers are under investigation in pre-clinical and clinical studies. Synthetic alkylphospholipids are anticancer agents that in contrast to most anticancer drugs, do not target DNA, but insert in the plasma membrane and subsequently induce a broad range of biological effects, ultimately leading to cell death. Alkylphospholipids kill tumor cells directly by induction of both apoptotic and non-apoptotic cell death, and indirectly by interference with critical signal transduction pathways involved in phospholipid metabolism and survival. Due to their distinct mode of action, these drugs are considered as attractive candidates to combine with radiotherapy. In this review, we will discuss several alkylphospholipids that reached clinical application. These include first-generation alkyl-lysophospholipids edelfosine and ilmofosine, second-generation alkylphosphocholine-prototype miltefosine and more recently developed analogues perifosine and erucylphosphocholine. We focus on mechanisms of action and the rationale to combine these agents with radiotherapy. The preclinical results on molecular targeting underlying this approach will be reviewed, concluded with first clinical data on combined treatment of radiotherapy with perifosine. PMID- 17287088 TI - Cortisol and severe fatigue: a longitudinal study in adolescent girls. AB - Fatigue is a common complaint among adolescents, especially in girls, and is associated with high rates of school absenteeism. Severe fatigue is often accompanied by psychological and physical symptoms. In the chronic fatigue syndrome (CFS) functioning of the hypothalamic-pituitary-adrenal (HPA)-axis has previously been found to be altered. The aim of the present study was to investigate whether cortisol production is deviant in fatigued adolescent girls from the general population and to study longitudinal changes in fatigue in association with possible changes in HPA-axis functioning. In the cross-sectional part of the study the cortisol response to awakening (CAR) and to a low-dose oral dexamethasone were examined in a group of fatigued adolescent girls (n=87) in comparison to a non-fatigued control group (n=77). Questionnaires regarding fatigue, depression, anxiety, sleep quality, somatic symptoms and CFS-related symptoms were filled out. Follow up measurements were performed after 6 and 12 months. While the fatigued and non-fatigued group differed remarkably on all symptom self-reports, no differences between groups in CAR and response to dexamethasone were observed. Girls in the fatigued group remained fatigued over time and reported high levels of other psychological and physical symptoms during the whole year of the study. The CAR varied between time points but correlated non-systematically with situational characteristics or symptom reports. We conclude that trait-like fatigue, as measured in a sample of adolescent girls from a high school population, is not reflected in a dysregulation as assessed on the level of salivary cortisol after awakening. PMID- 17287090 TI - A measure of nicotine dependence for smokeless tobacco users. AB - The objective of the present study was to examine the properties of a modification of the Fagerstrom Test of Nicotine Dependence in a large sample of smokeless tobacco (ST) users. The subjects for this study included 256 males who were recruited for a tobacco cessation intervention that involved a visit with a dentist and advice to quit smoking during the exam. At baseline, the modified dependence scale was administered to the participants and a saliva sample was collected to measure cotinine. The correlation between the total score and salivary cotinine was moderate among the ST only users (r=0.34), whereas it was lower (r=0.19) among the ST+cigarette users. Among ST only users, the coefficient alpha was 0.40; however it was considerably higher among the ST+cigarettes group (alpha=0.61). In both cases, the coefficient alpha was lower than the recommended value of 0.70. Future research should focus on refining questionnaires that more precisely measure nicotine dependence in smokeless tobacco users. PMID- 17287089 TI - Assessment of motivation to change substance use in dually-diagnosed schizophrenia patients. AB - Assessment of motivation to change substance use can be helpful in evaluating treatment readiness and outcome. However, the utility of self-report measures of motivation with schizophrenia patients is questionable. In the current study patients with schizophrenia and either concurrent cocaine dependence or remitted dependence completed the University of Rhode Island Change Assessment-Maryland (URICA-M), a self-report inventory that assesses motivation, and an analogous cartoon instrument at baseline and 6-months follow-up. Results demonstrate that the cartoon readiness to change score was related to increased treatment utilization and decreased substance use; results were not as favorable for the URICA-M. Findings suggest that the cartoon measure may be a suitable alternative to assess motivation to change substance use with cognitively impaired patients. PMID- 17287091 TI - Impulsivity and expectancy in risk for alcohol use: comparing male and female college students in Taiwan. AB - This was a longitudinal study designed to examine whether gender differences would exist in acquired preparedness model (APM) for explaining the risk of alcohol use in Chinese college students. Impulsivity was assessed for 3,584 students in 2002. In 2003, 1,377 students were traced and assessed in alcohol outcome expectancy, drinking behavior, and alcohol related problems, with 1,122 valid data (male=438). Separated by gender, the data was analyzed with the Structural Equation Model. Results showed that positive, not negative, outcome expectancy for alcohol mediated impulsivity's effect on alcohol use, and alcohol use had a direct effect on alcohol related problems in both males and females. In males, both negative and positive outcome expectancies failed to mediate impulsivity and alcohol related problems. In females, only positive outcome expectancy mediated the relation between impulsivity and alcohol related problems. This longitudinal data supported the acquired preparedness model for the risk in alcohol use among Chinese college students, providing a reference for designing prevention and intervention strategies guided towards both genders. PMID- 17287092 TI - Lithium and antidepressants: stimulating immune function and preventing and reversing infection. AB - The ability to safely and economically stimulate immune function would transform the humanitarian and economic landscapes of nosocomial, surgical and antibiotic resistant infections, as well as reduce the burden of epidemics, pandemics and bioterrorism. Such stimulation is widely held to be beyond our reach, an unfortunate misconception. As early as the mid 1980s sufficient evidence had accumulated to be able to state with conviction that lithium and antidepressants have these properties. Excessive production of prostaglandin E2 activates microorganisms and suppresses immune function, and lithium and antidepressants oppose prostaglandin E2. Immunostimulation is non-specific, possibly relevant to all infections, pertinent to one, two, or more concurrent infections, and highly cost/effective. In controlled studies an antidepressant would be relevant to that agent and only that agent, rendering such studies worthless. Over the past twenty years 22 drug companies have declined interest in developing antidepressants as antiinfectives. It would be unethical to deny the infected these well documented benefits. PMID- 17287093 TI - Wound healing in the context of mechanical strain: "Coupled pendulums" hypothesis. PMID- 17287094 TI - Epidural anaesthesia with levobupivacaine in patients undergoing major abdominal surgery. PMID- 17287095 TI - A critical damping approach for assessing the role of marrow fat on the mechanical strength of trabecular bone. AB - Several clinical findings revealed that post-menopausal osteoporosis and age related osteopenia are accompanied by trabecular bone marrow fat (BMF) increase. To help understand this phenomenon, a vibrating string model is proposed, based on the hypothesis that, when bone marrow properties change, the trabecular bone structure remodels itself to preserve its critical damping state. It is found that an inverse relationship holds between trabecular average length and marrow damping coefficient. Such a result leads us to hypothesize the following bone weakening mechanism. Since fat-rich bone marrow is a worse damper, a BMF increment causes an increase of trabecular average length, which is accomplished by the absorption of horizontal trabeculae (structurally less important than vertical trabeculae). The resulting bone patterns are in excellent agreement with clinical observations of osteoporotic bone. A definitive confirmation of the proposed mechanism will support a therapeutical approach to widespread osteopenic diseases aimed at avoiding, or limiting, BMF increase. PMID- 17287096 TI - Psychiatric predictors of adolescent and young adult drug use and abuse. PMID- 17287097 TI - Testosterone and cognitive function in ageing men: data from the Florey Adelaide Male Ageing Study (FAMAS). AB - OBJECTIVES: Recent evidence suggests that declining testosterone levels in ageing males may be associated with both normal and pathological cognitive ageing. The aim of the present analyses was to investigate whether endogenous gonadal steroid levels in males mediate or moderate the associations between age and performance on neuropsychological measures of verbal memory, executive function, and processing speed. METHODS: A cross-sectional analysis of the baseline data from 1046 community-dwelling men aged 35-80 years participating in the Florey Adelaide Male Ageing Study (FAMAS). Multiply adjusted analyses included participants' history of medical conditions, anthropometric measurements, medication use, smoking status, alcohol use and mood. Hormone measurements included total testosterone (TT), bioavailable testosterone (BT), calculated free testosterone (cEFT), oestradiol (E2), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH), and lutenising hormone (LH). Neuropsychological tests included the Fuld Object Memory Evaluation (FOME), Trails A and Trails B. RESULTS: In multiply adjusted analyses, higher cEFT and TT levels were associated with both poorer verbal memory and executive function performance and faster processing speed. cEFT levels were found to moderate the relationship between age and verbal memory performance quadratically and to mediate the relationship between age and processing speed. CONCLUSION: The results from this study suggest that higher levels of endogenous testosterone, particularly in the elderly, may have deleterious effects on cognitive functioning in men. PMID- 17287098 TI - Analytical detection and biological assay of antileukemic drug 5-fluorouracil using gold nanoparticles as probe. AB - Gold nanoparticles are reported and evaluated as probes for the detection of anticancer drug 5-fluorouracil (5FU). The nature of binding between 5FU and gold nanoparticles via complexation is investigated using ultraviolet visible spectrophotometry, cyclic voltammetry, transmission electron microscopy, fluorescence and Fourier transform infrared (FTIR) spectroscopy. The bound antileukemic drug is fluorescent and the quenching property of gold nanoparticles could be exploited for biological investigations. The 5FU-colloidal gold complex (Au@5FU) is observed to have appreciable antibacterial and antifungal activity against Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Aspergillus fumigatus, and Aspergillus niger. The experimental studies suggest that gold nanoparticles have the potential to be used as effective carriers for anticancer drugs. PMID- 17287099 TI - Formulation and characterization of curcuminoids loaded solid lipid nanoparticles. AB - Curcuminoids loaded solid lipid nanoparticles (SLNs) have been successfully developed using a microemulsion technique at approximately 75 degrees C. It was found that variation in the amount of ingredients had profound effects on the curcuminoid loading capacity, the mean particle size, and size distribution. At optimized process conditions, lyophilized curcuminoids loaded SLNs showed spherical particles with a mean particle size of approximately 450nm and a polydispersity index of 0.4. Up to 70% (w/w) curcuminoids incorporation efficacy was achieved. In vitro release studies showed a prolonged release of the curcuminoids from the solid lipid nanoparticles up to 12h following the Higuchi's square root model. After 6-month storage at room temperature in the absence of sunlight, the physical and chemical stabilities of the lyophilized curcuminoids loaded SLNs could be maintained, i.e. the mean particle size and the amount of curcuminoids showed no significant changes (P>0.05) compared to the freshly prepared SLNs. In addition, the chemical stability of curcuminoids incorporated into SLNs was further investigated by dispersing them into a model cream base. The results revealed that after storage in the absence of sunlight for 6 months, the percentages of the remaining curcumin, bisdemethoxycurcumin and demethoxycurcumin were 91, 96 and 88, respectively. PMID- 17287101 TI - Serum levels of cytokines and EEG findings in children with influenza associated with mild neurological complications. AB - We studied the relation among serum cytokine levels, EEG changes, and mild neurological complications (delirium and febrile seizure) in children with influenza. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble tumor necrosis factor receptor-1 (sTNFR-1) were measured in 27 children with proven influenza infection with mild neurological complications (10 patients with delirium and 17 with febrile seizures) and seven control children. EEG was recorded in 14 children with neurological complications. EEG showed focal slowing in four of nine patients with delirium and in four of five with febrile seizures. Generalized slowing was observed in one patient with delirium. The median serum IL-6 level was 31.2+/-15.1 pg/ml (range, 7.5-64.5 pg/ml) in the delirium group, 42.3+/-44.0 pg/ml (range, 8.0 196.0 pg/ml) in the febrile seizure group, and 15.4+/-7.0 pg/ml (range, 7.2-28.0 pg/ml) in the control group. Serum TNF-alpha and sTNFR-1 levels were not different among three groups. Mild neurological complications associated with influenza were related to the mildly abnormal serum IL-6 levels and EEG findings. The combination of these parameters will be useful for early diagnosis and differentiation of neurological complications in children with influenza. Further studies will be necessary for investigating that IL-6 has the diagnostic value for differentiation between severe encephalopathy and mild neurological complications in children with influenza. PMID- 17287100 TI - Pharmacological and toxicological studies of Drimys angustifolia Miers. (Winteraceae). AB - Drimys angustifolia Miers. (Winteraceae) is a Brazilian medicinal plant used as analgesic, antiulcer and anti-inflammatory without studies to assure its efficacy and safety Leaf and stem bark extracts were evaluated to determine the antiulcer, analgesic, antiinflammatory and antioxidant activities. Preliminary toxic effects and qualitative phytochemical profile were also performed. The antiulcer activity was detected in both extracts. Administration of the leaf extract at 250 mg/kg inhibited total lesion area by 76.50% (p < 0.01 in ethanol/HCl method), while carbenoxolone at 250 mg/kg reduced lesions by 69.48%. Stem bark extract (250 mg/kg) inhibited lesion by 81.42%, while carbenoxolone by 74.10%. Similar effects were observed in the ethanol-induced ulcer method, but no activity was observed in piroxican model. The effects involve nitric oxide in gastric protection, since the L-NAME treatment reversed the protection given by the extracts. Antioxidant effects suggest an involvement against oxidative stress. In the pain (writhing, tail-flick and hot-plate tests) and inflammation (carrageenan-induced paw edema) models, the extracts did not present any effect. The phytochemical studies demonstrated that both extracts contain flavonoids, saponins, glycosilated triterpenoids, fixed acids, cyanogenic glycosides, quinones, tannins, xanthone and steroidal aglycones. Toxicological studies showed that the extracts are safe at the effective antiulcer doses. PMID- 17287102 TI - Quantification of nitrated tryptophan in proteins and tissues by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. AB - Aromatic amino acids are targets of reactive nitrogen species (RNS) such as peroxynitrite (ONOO(-)) and nitrogen dioxide. It is known that tryptophan (Trp) as well as tyrosine is nitrated, generated isomers. However, no quantitative method to determine nitrotryptophan (NO(2)Trp) in proteins has been developed so far. In this study, we have developed a method for the quantification of Trp and NO(2)Trp isomers, 2-, 4- and 6-NO(2)Trp, which uses liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). In order to confirm the applicability of our method to in vitro and in vivo system, we measured protein-bound NO(2)Trp levels in ONOO(-) treated bovine serum albumin (BSA) and in liver of B6C3F1 mice at 2, 4, and 8h after administration of 300 mg/kg acetaminophen (APAP). A mass spectrometer equipped with an electrospray ionization source using a crossflow counter electrode and ran in the positive ion mode (ESI(+)) was used for multiple reaction monitoring (MRM) of transitions 205- >188, 250-->130, 250-->159 and 250-->233 for Trp, 2-, 4- and 6-NO(2)Trp, respectively. The recoveries from mice liver samples were 98.3-105.9% for each compound. The limits of quantification were 50, 3.0, 10 and 4.0 nM for Trp, 2-, 4 and 6-NO(2)Trp, respectively. In in vitro experiments demonstrated that all isomers of NO(2)Trp were detectable from BSA treated with ONOO(-) and the amount generated decreased in the order of 6-, 4- and 2-NO(2)Trp. In in vivo experiments, 4- and 6-NO(2)Trp were detected in the liver of mice administered APAP. The concentration range of 4- and 6-NO(2)Trp per mol of Trp in the sample was 2.24-3.92 and 26.96-32.71 nmol/mol of Trp, and its existence in vivo was confirmed for the first time with our method. The LC-ESI-MS/MS method was able to determine protein-bound NO(2)Trp in a small amount of tissue sample, and is therefore applicable not only as a biomarker of RNS, but also as a mean to clarify novel mechanisms underlying RNS-related tissue damage. PMID- 17287103 TI - Ultrastructural identification of oligodendrocyte/myelin proteins in corpus callosum of hypothyroid animals. AB - Thyroid hormone (T3) deficiency impairs the development of the CNS, particularly myelination. We have previously described an increase in the frequency of morphological abnormalities in the central myelin sheath in a hypothyroidism model, which reinforced the hypothesis of a role for T3 in myelin compaction. However, there are no data concerning the cellular distribution of myelin proteins in hypothyroid animals. In the present work, we describe the distribution of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin basic protein (MBP) and proteolipid protein (PLP) throughout the central myelin sheath of a hypothyroidism model. We used euthyroid and hypothyroid adult rats at 90 days of age. In order to induce hypothyroid status, animals received 0.02% methimazol from the 19th gestation day onwards. After perfusion with a fixative mixture, small pieces of corpus callosum were obtained, dehydrated and embedded in LR White resin. Ultrathin sections were immunoreacted, using specific antibodies revealed by a secondary antibody coupled to colloidal gold particles of 10nm. Gold particle density per region of myelin sheath for each one of these proteins was obtained. In normal animals, CNPase, PLP and MBP were identified in sites that had already been described in previous studies. In hypothyroid animals, CNPase was identified in the region corresponding to compact lamellae, which normally does not contain this protein, while, in this same region, PLP and MBP immunolabeling were decreased. These results suggest that thyroid hormone deficiency impairs the distribution of the major oligodendrocyte/myelin markers. This effect may justify the reduction in myelin sheath compaction previously demonstrated in a similar model of hypothyroidism. PMID- 17287104 TI - Incidence and prognostic influence of lymph node micrometastases in rectal cancer. AB - AIMS: The aim of this study was to determine the rate of lymph node micrometastases and evaluate their prognostic significance in rectal cancer. METHODS: Patients with either Dukes A or B rectal carcinoma who had undergone curative resection by either low anterior resection or abdominal perineal resection between 1991 and 2000 were selected from a prospectively collated database. None of the patients had metastasis at the time of surgery and none received adjuvant or neoadjuvant therapy. A single section from each lymph node was stained with haematoxylin and eosin (H+E) and with CAM 5.2 by immunohistochemistry. Statistical analyses were performed with Chi-square test. RESULTS: A total of 774 lymph nodes with a median of 14 lymph nodes per patient were examined, from a cohort of 56 patients with a median age of 66 years. In the 56 patients in whom lymph node metastases were not detected by haematoxylin-eosin staining, cytokeratin staining was positive in 15 lymph nodes from 10 patients. Nine patients had disease recurrence at a median follow-up of 98 months. The presence of lymph node micrometastases by immunohistochemistry did not predict either disease-free (p=0.44) or overall survival (p=0.63). CONCLUSION: Immunohistochemical staining detects micrometastases in rectal cancer which are not observed with H+E staining. However, no significant relationship was observed between disease relapse and rectal micrometastases detected by immunohistochemistry. PMID- 17287105 TI - Lymphoplasmacytic lymphoma associated with polyradiculoneuritis and cryoglobulinemia mimicking polyarteritis nodosa. AB - INTRODUCTION: Systemic vasculitis is sometimes associated with malignant blood disease. CASE: We describe the case of a 77-year-old woman who had extensive livedo racemosa, acute polyradiculoneuritis, and meningeal hemorrhage. The skin biopsy showed evidence of necrotizing angiitis. This vascular involvement resembled polyarteritis nodosa (PAN). Despite corticosteroid and cyclophosphamide treatment, the polyradiculoneuritis worsened and the patient died of acute respiratory failure. Type II cryoglobulinemia was detected late, and the autopsy revealed lymphoplasmacytic lymphoma involving the spleen and infiltrating nerve roots, together with necrotizing angiitis involving small-sized arteries. CONCLUSION: This case shows that necrotizing angiitis involving small arteries may occur with type II cryoglobulinemia. PMID- 17287106 TI - [Submitting studies without significant results]. AB - When a study finds that no exposure factor or therapy is significantly related to a given effect, researchers legitimately wonder if the results should be submitted for publication and to what journal. Clinical trials that report significant associations have a higher probability of publication, a phenomenon known as selective publication. The principal reasons of this selective publication include author self-censorship, peer-reviewing, trials not intended for publication, interpretation of the p value, cost of journal subscriptions, and policies. Subsequent reviews and meta-analyses are biased by the unavailability of nonsignificant results. Suggestions for preventing this risk include university training, trial registries, an international standard randomised controlled trial number (ISRCTN), Cochrane collaboration, and the gray literature. Journals (including electronic journals) interested in studies with nonsignificant results are listed. New technologies are changing the relations between publishers, libraries, authors and readers. PMID- 17287107 TI - [Treatment trial methodology in internal medicine]. AB - Clinical trials are the foundation of therapeutic evaluation. Their interpretation and usefulness depend on their compliance with strict methodological rules. Departments of internal medicine admit patients with many different diseases, a variety that makes it difficult to organize and conduct clinical trials in their standard form. This article reviews the rules of clinical trials that are essential to their validity and reliability. The prospective randomized double-blinded clinical trial is the most scientifically rigorous method for assessing treatment. Rare diseases and those involving several specialties can and should be performed in accordance with the standard methodological rules, despite their particular aspects. This article considers ways to improve the participation of departments of internal medicine to future clinical trials. PMID- 17287108 TI - Intra-uterine growth retardation after prenatal administration of Ginkgo biloba to rats. AB - Ginkgo biloba is a plant used in the treatment of Alzheimer's disease, cerebrovascular insufficiency and peripheral vascular diseases that showed reproductive toxicity in vitro and in the mouse model. In this study, pregnant Wistar rats received 0, 3.5, 7 and 14mg/kgbodyweight/day of G. biloba, by gavage, from the 8th to 20th day of pregnancy. Rats were killed on the 21st day and the following parameters were evaluated: maternal body weight; food and water intake; maternal's liver, kidney and ovary weights; resorption index; post-implantation loss; mean of live fetuses; fetuses and placenta mean weight; fetuses' liver, kidney, lung and brain weights; fetuses' external malformations. No significant alteration was observed in maternal parameters of toxicity, but the treatment with 7 and 14mg/kg/day of G. biloba caused significant decrease in the fetuses mean weights. The results indicated that G. biloba was not toxic to mothers, although it caused fetal intra-uterine growth retardation. PMID- 17287109 TI - Shp2 in PC12 cells: NGF versus EGF signalling. AB - The balance between specific signals from different growth factors dictates the biological response of mammalian cells including cell proliferation, differentiation and survival. PC12 cells represent a model of choice to compare the signalling of differentiative growth factors, as NGF, and of mitogenic growth factors, as EGF. In these cells the prolonged activity of the ERK kinase dictates the decision of cells to differentiate. Here we focused on the cytosolic tyrosine phosphatase Shp2 as an established regulator of the Ras-ERK cascade, to elucidate its involvement in determining the stimulation-dependent PC12 cell fate. To this end, we generated PC12 derived cell lines that express the interfering mutant of Shp2 under a tetracycline-inducible promoter. Our findings show that Shp2 participates to the opposite effects induced in PC12 cells by EGF and NGF and that the interactions with the multidocking Gab2 protein mediate such effects. PMID- 17287110 TI - Tracheostomy tape: more trouble than it's worth? AB - In many units where microvascular free-tissue transfer in the head and neck region is practised, tracheostomy is completed with the suturing of the tube in place and the removal of the supporting struts from the tube flange. The thinking is that in removing the struts the risk of occlusion of the vascular pedicle of the free flap, as it lies in the neck, is reduced as the cervical tape cannot be applied. The evidence base for vascular obstruction resulting from a correctly positioned tape is lacking. Presented here is a case in which potential flap failure, as a result of a cervical tracheostomy tape, was avoided by early detection of ischaemia using microdialysis. PMID- 17287111 TI - Widespread distribution of tetracycline resistance genes in a confined animal feeding facility. AB - We sought to determine the distribution of resistance and the tetracycline resistance genes among bacteria isolated from a swine confined animal feeding facility where tetracycline-containing feed had been in use for over 20 years. Samples collected from feed, hogs, hog houses, waste lagoon, soil, surface water and well water were screened for the presence of (a) resistant Escherichia coli and enterococci and (b) tetracycline-resistant strains of all species. Genomic DNA was extracted from the latter strain collection and fragments from 16S rDNA and ten tetracycline resistance genes (tetA, tetB, tetC, tetE, tetH, tetL, tetM, tetS, tetT and rumB) were polymerase chain reaction-amplified and a partial nucleotide sequence was obtained. In this environment, 77% of E. coli and 68% of enterococci isolated were tetracycline resistant. Tetracycline resistance was found in 26 different bacterial genera and in 60 species. Single resistance gene alleles (as defined by nucleotide sequence) were present in multiple species. There was evidence of gene recombination and multiple different tetracycline resistance genes were present in single bacterial isolates. These data provide further evidence for the widespread distribution of resistance genes in microbial populations in settings in which there is ongoing subtherapeutic antimicrobial use. PMID- 17287112 TI - Mutual physiological genetic mechanism of plant high water use efficiency and nutrition use efficiency. AB - Water deficiency and lower fertilizer utilization efficiency are major constraints of productivity and yield stability. Improvements of crop water use efficiency (WUE) and nutrient use efficiency (NUE) is becoming an important objective in crop breeding. With the introduction of new physiological and biological approaches, we can better understand the mutual genetics mechanism of high use efficiency of water and nutrient. Much work has been done in past decades mainly including the interactions between different fertilizers and water influences on root characteristics and crop growth. Fertilizer quantity and form were regulated in order to improve crop WUE. The crop WUE and NUE shared the same increment tendency during evolution process; some genes associated with WUE and NUE have been precisely located and marked on the same chromosomes, some genes related to WUE and NUE have been cloned and transferred into wheat and rice and other plants, they can enhance water and nutrient use efficiency. The proteins transporting nutrient and water were identified such as some water channel proteins. The advance on the mechanism of higher water and nutrient use efficiency in crop was reviewed in this article, and it could provide some useful information for further research on WUE and NUE in crop. PMID- 17287113 TI - Lipid composition greatly affects the in vitro surface activity of lung surfactant protein mimics. AB - A crucial aspect of developing a functional, biomimetic lung surfactant (LS) replacement is the selection of the synthetic lipid mixture and surfactant proteins (SPs) or suitable mimics thereof. Studies elucidating the roles of different lipids and surfactant proteins in natural LS have provided critical information necessary for the development of synthetic LS replacements that offer performance comparable to the natural material. In this study, the in vitro surface-active behaviors of peptide- and peptoid-based mimics of the lung surfactant proteins, SP-B and SP-C, were investigated using three different lipid formulations. The lipid mixtures were chosen from among those commonly used for the testing and characterization of SP mimics--(1) dipalmitoyl phosphatidylcholine:palmitoyloleoyl phosphatidylglycerol 7:3 (w/w) (PCPG), (2) dipalmitoyl phosphatidylcholine:palmitoyloleoyl phosphatidylglycerol:palmitic acid 68:22:9 (w/w) (TL), and (3) dipalmitoyl phosphatidylcholine:palmitoyloleoyl phosphatidylcholine:palmitoyloleoyl phosphatidylglycerol:palmitoyloleoyl phosphatidylethanolamine:palmitoyloleoyl phosphatidylserine:cholesterol 16:10:3:1:3:2 (w/w) (IL). The lipid mixtures and lipid/peptide or lipid/peptoid formulations were characterized in vitro using a Langmuir-Wilhelmy surface balance, fluorescent microscopic imaging of surface film morphology, and a pulsating bubble surfactometer. Results show that the three lipid formulations exhibit significantly different surface-active behaviors, both in the presence and absence of SP mimics, with desirable in vitro biomimetic behaviors being greatest for the TL formulation. Specifically, the TL formulation is able to reach low-surface tensions at physiological temperature as determined by dynamic PBS and LWSB studies, and dynamic PBS studies show this to occur with a minimal amount of compression, similar to natural LS. PMID- 17287114 TI - [HIV-1 drug resistance in French infected-children: from newborn to adolescent]. AB - Limit of antiretroviral treatment success is the emergence of drug-resistant virus. As reported in adult population, prevalence of resistance was high in treated HIV-infected children with detectable HIV viral load. Resistance increased with number of prior antiretroviral treatments, particularly with protease inhibitors. Adolescent boys seem at greater risk to harbor multi-classes resistant virus. In HIV-infected newborns, prevalence of resistance was 20%. Most of resistance mutations detected were in accord to perinatal antiretroviral exposition. Principal mechanism of resistance acquisition in newborns was transmission of resistant viruses from mother to child with early archive in cellular reservoir and long term persistence with or without treatment. Consequences of long term therapeutic strategies in children are major. PMID- 17287115 TI - RNAi for revealing and engineering plant gene functions. AB - RNA interference (RNAi) is now widely used in plant biotechnology, both as a useful tool for discovering or validating gene functions as well as a quick way of engineering specific reductions in expression of chosen genes. Although the amazing popularity of RNAi as a biotechnology tool is certainly justified, the underlying biology is still being worked out and the relative advantages and disadvantages of the approach are only now becoming clear. Recent breakthroughs in elucidating the multiple pathways of RNA-based post-transcriptional control and preliminary results from the first large-scale uses of RNAi in plants will make it easier to gauge the usefulness of the technique. To fully capitalize on the potential of RNAi, we need to become better at predicting and controlling its effects. PMID- 17287116 TI - Expression of splice variants of 1alpha-hydroxylase in mcf-7 breast cancer cells. AB - 1,25-Dihydroxyvitamin D(3) (calcitriol) is the most active natural metabolite of Vitamin D(3). It has strong antiproliferative and differentiating effects on various cell types including breast cancer cells. 25-Hydroxyvitamin D(3)-1alpha hydroxylase (1alpha-hydroxylase, CYP27B1) is one of the key enzymes in the formation of calcitriol. It has been found in breast cancer cells suggesting an autocrine regulation of formation of calcitriol in these cells. Alternative splicing of the encoding genes for this enzyme can possibly play a role in regulating the enzyme level and can explain tissue specific variations of 1alpha hydroxylase activity. Splice variants containing intron 1 may encode for truncated proteins with deletion of protein domains which are essential for its enzymatic activity. In order to obtain more information on the abundance of 1alpha-hydroxylase splice variants, we performed a highly specific nested touchdown PCR in MCF-7 cells. The full-length sequence of 1alpha-hydroxylase and two different splice variants of this enzyme containing intron 1 were isolated. By Western blot technique we then confirmed the protein products of the full length enzyme and its splice variants. We hypothesize that that the expression of splice variants can lead to a quantitatively lower expression of the mRNA of the full-length enzyme. The abundance of less active 1alpha-hydroxylase protein variants can alter the local synthesis of calcitriol in the cells and may explain variations of enzymatic activity in different cells and tissues. PMID- 17287117 TI - Vitamin D status and nutrition in Europe and Asia. AB - Vitamin D status is highly different in various countries of Europe, the Middle East and Asia. For this review, vitamin D deficiency is defined as serum 25 hydroxyvitamin D (25(OH)D) <25 nmol/l. Within European countries, serum 25(OH)D is <25 nmol/l in 2-30% of adults, increasing in the elderly and institutionalized to more than 80% in some studies. A north-south gradient was observed for serum 25(OH)D in the Euronut and MORE studies with higher levels in Scandinavia and lower levels in Italy and Spain and some Eastern European countries. This points to other determinants than sunshine, e.g. nutrition, food fortification and supplement use. Mean vitamin D intake in Scandinavia is 200-400IU/d, twice that in other European countries. Very low serum 25(OH)D levels have been reported in the Middle East, e.g. Turkey, Lebanon, Jordan and Iran. In these countries serum 25(OH)D was lower in women than in men and associated with clothing habits. In a Lebanese survey, vitamin D deficiency was observed in the majority and occurred mainly in veiled women. In India, vitamin D deficiency was observed in more than 30%, vitamin D status being poor in school children, pregnant women and large cities. Vitamin D status was much better in Malaysia and Singapore, but lower serum 25(OH)D was observed in Japan and China. Rickets and osteomalacia appear quite common in India, but precise data are lacking. Immigrants in Europe from the Middle East and Asia carry a high risk for vitamin D deficiency, pregnant women being especially at risk. Comparison of vitamin D status between countries is hampered by interlaboratory variation of serum 25(OH)D measurement. In addition, there is a need of population-based data. In conclusion, vitamin D deficiency is common in Southern Europe, the Middle East, India, China and Japan. It is less common in Northern Europe and Southeast Asia. Risk groups are young children, the elderly, pregnant women and non-western immigrants in Europe. Important determinants are skin type, sex, clothing, nutrition, food fortification, supplement use, BMI and degree of urbanization. PMID- 17287118 TI - Eleven years of experience reveals that fine-needle aspiration cytology is still a useful method for preoperative diagnosis of breast carcinoma. AB - Fine needle aspiration cytology (FNAC) has been used extensively for the diagnosis of breast lesions over the past 15 years. More recently, large gauge needle biopsy such as core biopsy has been used and the clinical value of FNAC has therefore been questioned. To answer this clinical question, we performed an 11-year study in which 1238 aspirates from patients with a breast lump were involved. In total, 1071 breast carcinomas were diagnosed with postoperative histological diagnosis. One thousand and forty-six of these 1071 breast carcinomas were definitely diagnosed by FNAC. Only one breast carcinoma identified by FNAC was not finally verified by histological diagnosis postoperatively. The diagnostic sensitivity, diagnostic specificity, overall accuracy, and the pseudo-negative and pseudo-positive results of FNAC for diagnosing breast carcinoma are 97.72%, 99.4%, 97.94%, 2.28%, and 0.6%, respectively. The method is rapid, accurate, and essentially complication-free, particularly in patients for neoadjuvant chemotherapy or endocrine therapy. The results suggest that FNAC is still a useful and reliable method for the preoperative diagnosis of breast carcinoma. PMID- 17287119 TI - Clinical research 1: Research questions and design. AB - This research series is aimed at clinicians who wish to develop research skills, or who have a particular clinical problem that they think could be addressed through research. The series aims to provide insight into the decisions that researchers make in the course of their work, and to also provide a foundation for decisions that nurses may make in applying the findings of a study to practice in their own Unit or Department. The series emphasises the practical issues encountered when undertaking research in critical care settings; readers are encouraged to source research methodology textbooks for more detailed guidance on specific aspects of the research process. PMID- 17287120 TI - The synthesis of alpha,beta-unsaturated carbonyl derivatives with the ability to inhibit both glutathione S-transferase P1-1 activity and the proliferation of leukemia cells. AB - Ethacrynic acid (EA), an alpha,beta-unsaturated carbonyl compound, is a glutathione S-transferase P1-1 (GSTP1-1) inhibitor. Twenty-one novel EA derivatives have been synthesized. The effects of these compounds on GSTP1-1 activity and on the proliferation of human leukemia HL-60 cells have been determined. Compounds with a halogen substitution at the 3'-position of the aromatic ring have greater inhibitory effects on GSTP1-1 activity than those of compounds with a methyl substitution there. Compounds with substitutions at both the 2'- and 3'-positions of the aromatic ring have more antiproliferative ability than those with one substitution at 3'-position. Esterification of the carboxyl group appears to increase the antiproliferative ability. PMID- 17287121 TI - Design, synthesis, inhibitory activity, and SAR studies of pyrrolidine derivatives as neuraminidase inhibitors. AB - A series of pyrrolidine derivatives were synthesized and evaluated for their ability to inhibit neuraminidase (NA) of influenza A virus (H3N2). All compounds were synthesized in good yields starting from commercially 4-hydroxy-L-proline using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A neuraminidase. Within this series, five compounds, 6e, 9c, 9e, 9f, and 10e, have good potency (IC(50)=1.56-2.71 microM) which are compared to that the NA inhibitor Oseltamivir (IC(50)=1.06 microM), and could be used as lead compoundS in the future. PMID- 17287122 TI - Discovery of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of potent and selective checkpoint kinase 1 inhibitors. AB - A new class of checkpoint kinase 1 (CHK-1) inhibitors bearing a 1,4 dihydroindeno[1,2-c]pyrazole core was developed after initial hits from high throughput screening. The efficient hit-to-lead process was facilitated by X-ray crystallography and led to potent inhibitors (<10nM) against CHK-1. X-ray co crystal structures of bound inhibitors demonstrated that two sub-series of this class of compounds, exemplified by 21 and 41, exhibit distinctive hydrogen bonding patterns in the specificity pocket of the active site. Two compounds, 41 and 43, were capable of potentiating doxorubicin and camptothecin, both DNA damaging agents, in cell proliferation assays (MTS and soft agar assays) and abrogating G2/M checkpoint in a mechanism-based FACS assay. PMID- 17287123 TI - Second generation of 5-ethenylbenzofuroxan derivatives as inhibitors of Trypanosoma cruzi growth: synthesis, biological evaluation, and structure activity relationships. AB - In vitro growth inhibitory activity of 21 new 5-ethenylbenzofuroxan derivatives against the protozoan parasite Trypanosoma cruzi, the causative agent of American trypanosomiasis, was studied. The designed compounds possess the previously described exigencies for optimal anti-parasite activity, the 5 ethenylbenzofuroxanyl moiety with different substituents. The synthetic key for preparing the derivatives was the Wittig procedure, that when 5 formylbenzofuroxan was used as the electrophile the corresponding deoxygenated products were marginally generated. Four of the new derivatives displayed remarkable in vitro activities against the epimastigote form of three strains of T. cruzi, Tulahuen 2, CL Brener, and Y. While the three deoxygenated analogues biologically assayed resulted inactives. Unspecific cytotoxicity was evaluated using human macrophages and active derivatives were not toxic at a concentration at least 13 times that of its IC(50) against T. cruzi (CL Brener strain). From the preliminary structure-activity relationship studies lipophilicity and electronic requirements were found relevant to anti-T. cruzi activity. Active compounds are more lipophilic than inactive ones and it was also identified that an optimum value of R Swain-Lupton's descriptor is required for optimal activity. PMID- 17287124 TI - Synthesis of dioxane-based antiviral agents and evaluation of their biological activities as inhibitors of Sindbis virus replication. AB - The crystal structure of the Sindbis virus capsid protein contains one or two solvent-derived dioxane molecules in the hydrophobic binding pocket. A bis dioxane antiviral agent was designed by linking the two dioxane molecules with a three-carbon chain having R,R connecting stereochemistry, and a stereospecific synthesis was performed. This resulted in an effective antiviral agent that inhibited Sindbis virus replication with an EC(50) of 14 microM. The synthesis proceeded through an intermediate (R)-2-hydroxymethyl-[1,4]dioxane, which unexpectedly proved to be a more effecting antiviral agent than the target compound, as evidenced by its EC(50) of 3.4 microM as an inhibitor of Sindbis virus replication. Both compounds were not cytotoxic in uninfected BHK cells at concentrations of 1mM. PMID- 17287125 TI - Synthesis of S-dialkylarsino-3-mercapto-1,2-propanediols and evaluation of their anticancer activity. AB - Some new S-dialkylarsenic compounds, S-dialkylarsino-3-mercapto-1,2-propanediol (3a-3d) and their derivatives (4a,4b), have been synthesized. They were screened at the National Cancer Institute (NCI) for their anticancer activity against a panel of about 60 human tumor cell lines. Most of them display anticancer activity having GI(50) and LC(50) values at low concentrations and are sensitive to leukemia, renal cancer and prostate cancer cell lines and in which the compound 3c is the most active. PMID- 17287126 TI - Synthesis of DL-standishinal and its related compounds for the studies on structure-activity relationship of inhibitory activity against aromatase. AB - DL-Standishinal (1), an aromatase inhibitor isolated from Thuja standishii, was synthesized in 15 steps from p-formylanisole via aldol reaction of 12-hydroxy-6,7 secoabieta-8,11,13-trien-6,7-dial (2). In the present study, we found that the aldol condensation of 2 proceeded in excellent yield with the protonic catalyst such as d-camphorsulfonic acid in CH(2)Cl(2). Moreover, structure-activity relationship of 1 and its related compounds was studied and it was revealed that the isomers having cis-configuration on the A/B-ring generally exhibited more potent inhibitory activities against aromatase than those with trans configuration. PMID- 17287127 TI - Identification of tyrosinase inhibitors from Marrubium velutinum and Marrubium cylleneum. AB - Tyrosinase is a key enzyme in the production of melanins in plants and animals. Forty-five secondary metabolites isolated from Marrubium velutinum and Marrubium cylleneum belonging to the classes of flavonoids, phenylethanoid glycosides, phenolic acids and lignan glycosides were screened for their inhibitory activity against mushroom tyrosinase. Flavonoids and phenylethanoid glycosides showed moderate inhibitory activity, while phenolic acids were less active than phenylethanoid glycosides, suggesting that both phenolic groups are important for the activity. PMID- 17287128 TI - A multi-centre additive and logistic risk model for in-hospital mortality following aortic valve replacement. AB - OBJECTIVE: To develop a multivariate prediction model for in-hospital mortality following aortic valve replacement. METHODS: Retrospective analysis of prospectively collected data on 4550 consecutive patients undergoing aortic valve replacement between 1 April 1997 and 31 March 2004 at four hospitals. A multivariate logistic regression analysis was undertaken, using the forward stepwise technique, to identify independent risk factors for in-hospital mortality. The area under the receiver operating characteristic (ROC) curve was calculated to assess the performance of the model. The statistical model was internally validated using the technique of bootstrap resampling, which involved creating 100 random samples, with replacement, of 70% of the entire dataset. The model was also validated on 816 consecutive patients undergoing aortic valve replacement between 1 April 2004 and 31 March 2005 from the same four hospitals. RESULTS: Two hundred and seven (4.6%) in-hospital deaths occurred. Independent variables identified with in-hospital mortality are shown with relevant co efficient values and p-values as follows: (1) age 70-75 years: 0.7046, p<0.001; (2) age 75-85 years: 1.1714, p<0.001; (3) age>85 years: 2.0339, p<0.001; (4) renal dysfunction: 1.2307, p<0.001; (5) New York Heart Association class IV: 0.5782, p=0.003; (6) hypertension: 0.4203, p=0.006; (7) atrial fibrillation: 0.604, p=0.002; (8) ejection fraction<30%: 0.571, p=0.012; (9) previous cardiac surgery: 0.9193, p<0.001; (10) non-elective surgery: 0.5735, p<0.001; (11) cardiogenic shock: 1.1291, p=0.009; (12) concomitant CABG: 0.6436, p<0.001. Intercept: -4.8092. A simplified additive scoring system was also developed. The ROC curve was 0.78, indicating a good discrimination power. Bootstrapping demonstrated that estimates were stable with an average ROC curve of 0.76, with a standard deviation of 0.025. Validation on 2004-2005 data revealed a ROC curve of 0.78 and an expected mortality of 4.7% compared to the observed rate of 4.1%. CONCLUSIONS: We developed a contemporaneous multivariate prediction model for in hospital mortality following aortic valve replacement. This tool can be used in day-to-day practice to calculate patient-specific risk by the logistic equation or a simple scoring system with an equivalent predicted risk. PMID- 17287129 TI - Pharmacokinetics of rituximab and its clinical use: thought for the best use? AB - Rituximab (MabThera, Rituxan) is a chimaeric monoclonal antibody increasingly used in the treatment of B-lymphoproliferative disorders and autoimmune diseases. Rituximab is now associated with chemotherapy for the treatment of non-Hodgkin's lymphoma and should be approved soon in maintenance strategies. During its rapid clinical development, rituximab schedules were dictated more often by logistical rather than by scientific considerations. In addition, early clinical phases have shown that rituximab exposure was variable in patients receiving similar doses and that clinical response was related to rituximab concentrations. There is however limited information on rituximab pharmacokinetics and on factors influencing individual exposure to this monoclonal antibody, although a better understanding of these factors is needed to optimise its dosing regimen. This review focuses on the current knowledge on rituximab pharmacokinetics and on factors influencing individual exposure and suggests ways to improve its clinical use. PMID- 17287130 TI - Soybean disease resistance protein RHG1-LRR domain expressed, purified and refolded from Escherichia coli inclusion bodies: preparation for a functional analysis. AB - Introduction and expression of foreign genes in bacteria often results accumulation of the foreign protein(s) in inclusion bodies (IBs). The subsequent processes of refolding are slow, difficult and often fail to yield significant amounts of folded protein. RHG1 encoded by rhg1 was a soybean (Glycine max L. Merr.) transmembrane receptor-like kinase (EC 2.7.11.1) with an extracellular leucine-rich repeat domain. The LRR of RHG1 was believed to be involved in elicitor recognition and interaction with other plant proteins. The aim, here, was to express the LRR domain in Escherichia coli (RHG1-LRR) and produce refolded protein. Urea titration experiments showed that the IBs formed in E. coli by the extracellular domain of the RHG1 protein could be solubilized at different urea concentrations. The RHG1 proteins were eluted with 1.0-7.0M urea in 0.5M increments. Purified RHG1 protein obtained from the 1.5 and 7.0M elutions was analyzed for secondary structure through circular dichroism (CD) spectroscopy. Considerable secondary structure could be seen in the former, whereas the latter yielded CD curves characteristic of denatured proteins. Both elutions were subjected to refolding by slowly removing urea in the presence of arginine and reduced/oxidized glutathione. Detectable amounts of refolded protein could not be recovered from the 7.0M urea sample, whereas refolding from the 1.5M urea sample yielded 0.2mg/ml protein. The 7.0M treatment resulted in the formation of a homogenous denatured state with no apparent secondary structure. Refolding from this fully denatured state may confer kinetic and/or thermodynamic constraints on the refolding process, whereas the kinetic and/or thermodynamic barriers to attain the folded conformation appeared to be lesser, when refolding from a partially folded state. PMID- 17287132 TI - Human stratum corneum lipid organization as observed by atomic force microscopy on Langmuir-Blodgett films. AB - The barrier function of skin ultimately depends on the physical state and structural organisation of the stratum corneum extracellular lipid matrix. Ceramides, cholesterol and a broad distribution of saturated long-chain free fatty acids dominate the stratum corneum lipid composition. Additionally, smaller amounts of cholesterol sulfate and cholesteryl oleate may be present. A key feature determining skin barrier capacity is thought to be whether or not different lipid domains coexist laterally in the stratum corneum extracellular lipid matrix. In this study, the overall tendency for lipid domain formation in different mixtures of extracted human stratum corneum ceramides, cholesterol, free fatty acids, cholesterol sulfate and cholesteryl oleate were studied using atomic force microscopy (AFM) on Langmuir-Blodgett (LB) films on mica. It is shown that the saturated long-chain free fatty acid distribution of human stratum corneum prevents hydrocarbon chain segregation. Further, LB-films of human stratum corneum ceramides express a pattern of connected elongated domains with a granular domain interface. The dominating effect of both cholesterol and cholesterol sulfate is that of increased ceramide domain dispersion. This effect is counteracted by the presence of free fatty acids, which preferentially mix with ceramides and not with cholesterol. Cholesteryl oleate does not mix with other skin lipid components, supporting the hypothesis of an extra-endogenous origin. In the system composed of endogenous human ceramides and cholesterol plus 15 wt% stratum corneum distributed free fatty acids, i.e., the system mimicking most closely the lipid composition of the stratum corneum extracellular space, LB films on mica express lateral domain formation. PMID- 17287131 TI - Purification of recombinant human interferon-epsilon and oligonucleotide microarray analysis of interferon-epsilon-regulated genes. AB - Recently identified interferon-epsilon (IFN-epsilon) belongs to type I interferons. IFN-epsilon is highly and constitutively expressed in the brain, but its biochemical and biological characteristics are poorly understood. In this study, full-length IFN-epsilon cDNA was cloned from human peripheral blood lymphocyte by RT-PCR, and was expressed in Escherichia coli (E. coli). Reverse phase high pressure liquid chromatography was used to purify recombinant human IFN-epsilon (rhIFN-epsilon) and to facilitate refolding of the protein. About 0.8mg of highly purified rhIFN-epsilon protein was obtained from 100ml of E. coli culture. Functional study of rhIFN-epsilon demonstrated that the antiviral activity of rhIFN-epsilon was 6+/-0.5x10(5)IU/mg, which was lower than that of rhIFN-alpha-2b in the WISH-VSV (WISH cells infected with vesicular stomatitis virus) assay system. As for the activity to promote NK cytotoxicity and antiproliferation activities, rhIFN-epsilon was about 60 times less potent than rhIFN-alpha-2b. However, oligonucleotide microarray analyses revealed dramatic differences in gene expression profiles of cultured human cells treated with IFN epsilon and IFN-alpha-2b. Particularly, differential regulation of genes related to central nervous system by rhIFN-epsilon suggests a role for IFN-epsilon in maintenance of the structure and function of brain. PMID- 17287133 TI - Fatigue-induced changes in muscle fiber action potentials estimated by wavelet analysis. AB - We aimed to investigate fatigue-induced changes in the spectral parameters of slow (SMF) and fast fatigable muscle fiber (FMF) action potentials using discrete wavelet (DWT) and fast Fourier (FFT) transforms. Intracellular potentials were recorded during repetitive stimulation of isolated muscle fibers immersed in Ca(2+)-enriched medium, while extracellular potentials were obtained from muscle fibers pre-exposed to electromagnetic microwaves (MMW, 2.45 GHz, 20 mW/cm(2)). The changes in the frequency distribution of the action potentials during the period of uninterrupted fiber activity were used as criteria for fatigue assessment. The wavelet coefficients' changes in the calculated frequency scales demonstrated a contribution of the increased [Ca(2+)](0) to an earlier compression of the frequency spectrum towards lower ranges. Root mean square (RMS) analysis of the wavelet coefficients calculated from SMF potentials showed a reduction of the higher frequencies (scale 1) by 90% in elevated [Ca(2+)](0) vs. 55% in controls and an increase of low frequencies (scale 5) by 323% vs. 187%, respectively. For FMF potentials a decrease of 71% vs. 59% for high frequencies (scale 1, elevated [Ca(2+)](0) vs. control) and an increase of 386% vs. 295% in scale 5, respectively, were observed. MMW pre-exposure resulted in increased muscle fiber resistance to fatigue. The fatigue-induced decrease of potential high frequencies (SMF: 59% vs. 96%, MMW vs. control; FMF: 30% vs. 92%, respectively), and the increase of low frequencies (SMF: 200% vs. 207%, MMW vs. control; FMF: 93% vs. 314%, respectively) were significantly smaller and delayed in exposed muscle fibers. Data from RMS analysis indicate that DWT provides a reliable method for estimation of muscle fatigue onset and progression. PMID- 17287135 TI - Cystic fibrosis presenting with bilateral facial palsy. AB - A 15-week old male infant presented with bilateral lower motor neuron facial palsy of unknown cause. Subsequently his growth deteriorated and he developed progressively worsening cough and wheeze. A diagnosis of cystic fibrosis was confirmed and hypovitaminosis A detected. Improvement of the facial palsy was noted following standard management of cystic fibrosis including vitamin A supplementation. PMID- 17287136 TI - Beta-adrenergic activation of solute coupled water uptake by toad skin epithelium results in near-isosmotic transport. AB - Transepithelial potential (V(T)), conductance (G(T)), and water flow (J(V)) were measured simultaneously with good time resolution (min) in isolated toad (Bufo bufo) skin epithelium with Ringer on both sides. Inside application of 5 microM isoproterenol resulted in the fast increase in G(T) from 1.2+/-0.3 to 2.4+/-0.4 mS x cm(-2) and slower increases in equivalent short circuit current, I(SC)(Eqv) = -G(T) x V(T), from 12.7+/-3.2 to 33.1+/-6.8 microA cm(-2), and J(V) from 0.72+/ 0.17 to 3.01+/-0.49 nL cm(-2) s(-1). Amiloride in the outside solution abolished I(SC)(Eqv) (-1.6+/-0.1 microA cm(-2)) while J(V) decreased to 0.50+/-0.15 nL cm( 2) x s(-1), which is significantly different from zero. Isoproterenol decreased the osmotic concentration of the transported fluid, C(osm) approximately 2 x I(SC)(Eqv)/J(V), from 351+/-72 to 227+/-28 mOsm (Ringer's solution: 252.8 mOsm). J(V) depicted a saturating function of [Na+]out in agreement with Na+ self inhibition of ENaC. Ouabain on the inside decreased I(SC)(Eqv) from 60+/-10 to 6.1+/-1.7 microA cm(-2), and J(V) from 3.34+/-0.47 to 1.40+/-0.24 nL cm(-2) x s( 1). Short-circuited preparations exhibited a linear relationship between short circuit current and J(V) with a [Na+] of the transported fluid of 130+/-24 mM ([Na+]Ringer's solution = 117.4 mM). Addition of bumetanide to the inside solution reduced J(V). Water was transported uphill and J(V) reversed at an excess outside osmotic concentration, deltaC(S,rev) = 28.9+/-3.9 mOsm, amiloride decreased deltaC(S,rev) to 7.5+/-1.5 mOsm. It is concluded that water uptake is accomplished by osmotic coupling in the lateral intercellular space (lis), and hypothesized that a small fraction of the Na+ flux pumped into lis is recirculated via basolateral NKCC transporters. PMID- 17287134 TI - Sleep disturbances in caregivers of persons with dementia: contributing factors and treatment implications. AB - Estimates suggest that there are more than 10 million adult caregivers of persons with dementia, two-thirds of who experience some form of sleep disturbance during the course of their caregiving career. Health care professionals are in the best position to detect and address this significant public health problem. Three major contributors to caregiver sleep disturbance are discussed in this paper: (1) the presence of caregiver disrupted sleep routines; (2) caregiver burden and depression; and, (3) the caregiver's physical health status. Successful treatment of a caregiver's sleep disturbance requires careful consideration of each of these contributors. We review and analyze the scientific literature concerning the multiple complex factors associated with the development and maintenance of sleep disturbances in caregivers. We provide a clinical vignette that illustrates the interplay of these contributing factors, and close by providing recommendations for clinicians and researchers treating and investigating the development and maintenance of sleep problems in family caregivers. PMID- 17287137 TI - Expression analysis of two types of transcripts from circadian output gene lark in Bombyx mori. AB - We analyzed expression patterns of lark (Bmlark) in Bombyx mori. Southern blot analysis demonstrated that Bmlark was a single copy gene. Northern blot analyses revealed two types of Bmlark transcripts, one being of 1.38 kb (Bmlark-PA) and the other of 0.85 kb (Bmlark-PB). Both transcripts were detected in the eggs, larval and adult heads, testes, ovaries and flight muscles. Both types of transcripts are constitutively expressed with no clear rhythmicity in the adult heads under light:dark (LD) cycles but the amount of the Bmlark-PA transcript was twice as much as that of the Bmlark-PB transcript in the adult heads throughout a day. Real-Time PCR assays also indicated constant expressions of the two types of Bmlark in the pupal brains under LD12:12 and LD16:8. PMID- 17287138 TI - Metabolic fates of yolk lipid and individual fatty acids during embryonic development of the coot and moorhen. AB - There is currently little information regarding the metabolic fates of yolk lipid and individual fatty acids during embryonic development of free-living avian species. Here we report the pattern of lipid utilization during embryonic development of the coot (Fulica atra) and the moorhen (Gallinula chloropus), two related species producing precocial offspring from eggs with a distinctive fatty acid composition and with an incubation period similar to that of the chicken. By the time of hatching, the proportions of the initial yolk lipid that had been transferred to the embryo were 88.2% and 79.8% for the coot and moorhen respectively. During the whole incubation period, 42.9% and 40.0% of the initial yolk lipid of the coot and moorhen respectively were lost from the system due to oxidation for energy, equating to 47.8% and 50.0% respectively of the actual amount of lipid transferred over this time. Thus, the lipid received by the embryos of both species is partitioned almost equally between the alternative fates of energy metabolism and incorporation into tissue lipids. In the coot, this 50:50 split between oxidation and tissue formation was maintained during the hatching process. The proportions of arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) in the yolk lipids of these species were 2.5-3.5 times higher than in eggs of domestic poultry. In contrast to the situation in the chicken, there was no preferential uptake of 22:6n-3 from the yolk during coot and moorhen development. The fatty acid compositions of the whole body lipids of the coot and moorhen hatchlings were almost identical to those of the initial yolks indicating that, unlike the chicken, these species display relatively little overall biomagnification of 20:4n-6 and 22:6n-6 during development. It is suggested that the yolk fatty acid profiles of the coot and moorhen are particularly well matched to the requirements of the embryo, reducing the need for selective uptake of 22:6n-3 and for the overall biomagnification of 22:6n-3 and 20:4n-6. PMID- 17287139 TI - S18Y in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) associated with decreased risk of Parkinson's disease in Sweden. AB - Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that removes ubiquitin from the C-terminal end of substrates and a component of the ubiquitin-proteasome system. A protective effect of a UCH-L1 variant, S18Y, was suggested since the common variant was found to be inversely associated with sporadic Parkinson's disease (PD). We investigated the association of S18Y in our Swedish PD material. The tyrosine variant was significantly inversely associated with PD (P=0.049) and with a low age of onset (50 years) (P=0.017) in the case control material, supporting the hypothesis of a protective function. PMID- 17287140 TI - Task-specific focal hand dystonia with usage of a spoon. AB - We describe a 30-year-old woman who suffered from an unusual task-specific focal hand dystonia, which dominantly occurred with use of a spoon; there were no other activities affected, except for mild writer's dystonia on same side. This is the first report of a spoon-related focal dystonia. PMID- 17287141 TI - Stress-induced morphogenic responses: growing out of trouble? AB - Plants exposed to sub-lethal abiotic stress conditions exhibit a broad range of morphogenic responses. Despite the diversity of phenotypes, a generic 'stress induced morphogenic response' can be recognized that appears to be carefully orchestrated and comprises three components: (a) inhibition of cell elongation, (b) localized stimulation of cell division and (c) alterations in cell differentiation status. It is hypothesized that the similarities in the morphogenic responses induced by distinct stresses, reflect common molecular processes such as increased ROS-production and altered phytohormone transport and/or metabolism. The stress-induced morphogenic response (SIMR) is postulated to be part of a general acclimation strategy, whereby plant growth is redirected to diminish stress exposure. PMID- 17287143 TI - The experiences of teenagers and young adults with cancer--results of 2004 conference survey. AB - In 2004, 350 teenagers and young adults (TYAs) attended the third Find Your Sense of Tumour Conference for cancer patients. This provided a unique opportunity to survey a large group of patients regarding their cancer experience. Analysis of the results showed that delegates had both positive and negative experiences of the cancer journey and had clear views regarding service provision. The survey showed that the majority of TYAs with or who have had cancer would like to be treated on a specialist unit. There are currently 7 Teenage and Young Adult Units developed by Teenage Cancer Trust within the UK; however, a large number of patients do not have access to these specialist services. Despite the increased attention to TYA health needs there are still a number of issues relating to cancer services that need addressing as a matter of urgency in order to ensure that future patients receive a timely diagnosis, together with appropriate care that meets the specific needs of this unique client group. PMID- 17287142 TI - One, two, three--p53, p63, p73 and chemosensitivity. AB - Molecular links between apoptosis, tumorigenesis and drug resistance provide starting points for new therapeutic approaches and for a targeted cancer therapy. The discovery of the p53-related genes p63 and p73 raised the possibility that they may be cancer-associated genes and as a consequence that p53 is not the only component in predicting prognosis and response to chemotherapy, but instead the status of a network that contains p53, p73 and p63. This review focuses on the status and interrelationship of the p53 family members in human cancer as critical elements for tumor progression and response to therapy. Literature up to December 2006 is reviewed. p63 and p73--as well as p53--each use multiple promoters and alternative splicing to generate an array of isoforms, including full-length isoforms with a transactivation (TA-) domain homologous to that of full-length p53, and amino-terminally truncated (DeltaN-) isoforms. Whereas the full-length TA isoforms of p63 and p73 can activate downstream target genes and induce apoptosis, the DeltaN isoforms which lack the transactivation domain can act as dominant inhibitors of the full-length forms of p53, p63 and p73, inhibiting transactivation of target genes and induction of apoptosis. Deregulated dominant negative p63 and p73 isoforms play an oncogenic role in human cancer and contribute to chemoresistance. Thus, therapeutic modulation of TAp63/DeltaNp63, TAp73/DeltaNp73 and mutant p53 levels might be used to target the large percentage of human tumors that harbor p53 mutations and/or overexpress DeltaNp63 or DeltaNp73. Interfering with the expression or function of DeltaNp63 and/or DeltaNp73 and/or mutant p53 in tumor cells may render such tumors more responsive to therapy and reduce their aggressiveness and metastatic capacity. PMID- 17287144 TI - Unusual features of the cell cycle in mycobacteria: polar-restricted growth and the snapping-model of cell division. AB - Cell division patterns in mycobacteria have been examined in order to further our understanding of how these important organisms grow in the apparent absence of key systems required for the growth of rod-shaped bacteria. Analysis of the distribution of cell lengths in the population during different phases of growth showed that the modal cell length decreases during later phases of growth, declining from 3.5 to 2.5 microm for Mycobacterium bovis BCG cells sampled in log phase and stationary phase, respectively. The population also became more homogeneous, as indicated by the proportion of cells in the most common class increasing from 15% to 28%. Similar patterns were observed for Mycobacterium smegmatis and Mycobacterium tuberculosis. Consistent with other actinomycetes, and in contrast to most rod-shaped bacteria, the deposition of newly synthesised peptidoglycan in mycobacteria is restricted to the poles of the cell, as evidenced by staining with fluorescently labelled vancomycin. A "V-form" of bacteria was observed in cultures at all stages of growth, but the proportion decreased in older cultures. The V-shape appears to be a result of the uneven splitting of the exterior cell envelope at the new septum; this exposes the new peptidoglycan which is illustrated by spots of fluorescent vancomycin staining associated with the exterior side of the "V", and supports the 'snapping division model'. The restriction of growth to the poles of the cell differs from the pattern observed in other rod-shaped bacteria, in which the cell poles are inert and lateral growth occurs by deposition of peptidoglycan along the body of the cylinder. The mechanisms that maintain the shape of mycobacteria and that identify the mid-point for cell division remain to be determined. PMID- 17287145 TI - Walker 256 tumor-bearing rats as a model to study cancer pain. AB - An animal model of cancer pain induced by injection of Walker 256 carcinoma cells into the plantar surface of rat hind paw is described. Tumor growth and the occurrence of metastasis were investigated by histopathological analysis. Tumor cell growth was also analyzed plethysmographically by the increase in paw volume. For characterization of pain symptoms, hyperalgesia, allodynia, and spontaneous pain were evaluated 5 to 8 days after cell injection. The volume of the inoculated paw started to increase on day 2 after inoculation, being 40% higher on day 5 after injection. At this time, there was a marked proliferation of tumor cells, with the presence of anaplastic and pleomorphic cells, nucleoli, and atypical mitotic features. On days 7 and 8 after injection, histopathological analysis of popliteal lymph nodes showed the presence of tumor cells. The intraplantar injection of Walker 256 cells caused hyperalgesia at day 5 after cell inoculation. Low-threshold mechanical allodynia was significant 2 days after cell injection, being increased on day 5. In addition, inoculation of tumor cells induced gross behavior, characterized by a significant increase in licking and lifting of the injected paw 5 days after injection. The pain-enhancing effect caused by cell inoculation was partially inhibited by indomethacin on day 2 after cell injection, whereas morphine blocked allodynia on days 2 and 5. These results indicate that intraplantar injection of Walker 256 cells cause pain symptoms characteristic of cancer pain. This experimental model can then be used to investigate new analgesic or anti-tumor drugs. PERSPECTIVE: This article presents a new animal model for studying cancer pain and metastasis. This model could help in understanding the mechanisms involved in cancer pain symptoms and may be used for the investigation of new analgesic or anti-tumor drugs. PMID- 17287147 TI - Changes in tissue defence system in white spot syndrome virus (WSSV) infected Penaeus monodon. AB - The present study examined the changes occurring in the pro phenoloxidase system and antioxidant defence status in haemolymph, hepatopancreas and muscle tissue of white spot syndrome virus (WSSV) infected Penaeus monodon. Tiger shrimps (P. monodon) were infected with white spot virus by intramuscular injection of the virus inoculum. Levels of lipid peroxides and the activities of phenoloxidase, glutathione-dependent antioxidant enzymes [glutathione peroxidase (GPX), glutathione-S-transferase (GST)] and antiperoxidative enzymes [superoxide dismutase (SOD) and catalase (CAT)] were determined. WSSV infection induced a significant increase in lipid peroxidation in haemolymph, muscle and hepatopancreas of experimental P. monodon compared to normal controls. This was paralleled by significant reduction in the activities of phenol oxidase, glutathione-dependent antioxidant enzymes and antiperoxidative enzymes. The results of the present study indicate that the tissue antioxidant defence system in WSSV infected P. monodon is operating at a lower rate, which ultimately resulted in the failure of counteraction of free radicals, leading to oxidative stress as evidenced by the increased level of lipid peroxidation. PMID- 17287146 TI - Rodent brain and heart catecholamine levels are altered by different models of copper deficiency. AB - Limiting dopamine beta-monooxygenase results in lower norepinephrine (NE) and higher dopamine (DA) concentrations in copper-deficient Cu- tissues compared to copper-adequate Cu+ tissues. Mice and rat offspring were compared to determine the effect of differences in dietary copper Cu deficiency started during gestation or lactation on catecholamine, NE and DA, content in brain and heart. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu- diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 12 and 27. For both rat and mouse Cu- tissue, NE and DA changes were greater at later ages. Though Cu restriction began earlier in rats than mice in the gestational model, brain NE reduction was more severe in Cu mice than Cu- rats. Cardiac NE reduction was similar in Cu- rodents in the gestation models. In the lactation model, mouse catecholamines were altered more than rat catecholamines. Furthermore, following lactational Cu deficiency Cu- mice were anemic and exhibited cardiac hypertrophy, Cu- rats displayed neither phenotype. Within a species, changes were more severe and proportional to the length of Cu deprivation. Lactational Cu deficiency in mice had greater consequences than in rats. PMID- 17287148 TI - Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. AB - BACKGROUND & AIMS: Insulin resistance has been implicated in the pathogenesis of both nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). We hypothesized that NAFLD would be common in both obese and nonobese women with PCOS. The aim of this study was to estimate the prevalence of and identify associated factors for hepatic steatosis in women with PCOS. METHODS: This is a retrospective study of 88 consecutive premenopausal women with PCOS. Clinical history, height, weight, and laboratory values were obtained. Fasting measurements of serum glucose and insulin were used to calculate homeostasis model assessment of insulin resistance (HOMA-IR). Abdominal ultrasonography was used to determine the presence and severity of hepatic steatosis. RESULTS: Of the 88 women (median age, 31.4 years), 48 (55%) had steatosis; 15 (39%) of them were lean women. The presence of steatosis was associated with a greater body mass index (BMI) (P = .005) and HOMA-IR (P = .033), a lower fasting high-density lipoprotein (P = .003), and a greater prevalence of impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus (P = .013). Only 7 (15%) subjects with hepatic steatosis had abnormal liver chemistries. CONCLUSIONS: Fatty liver was identified in 55% of subjects with PCOS, nearly 40% of whom were lean women. High BMI and insulin resistance appeared to be important associated factors. Early recognition of NAFLD in this group of young patients is warranted, and further investigation including liver biopsy might be indicated. PMID- 17287149 TI - Effects of an exercise intervention on other health behaviors in overweight/obese post-menopausal women. AB - BACKGROUND: Little is known about whether initiating physical activity induces change in other health-related behaviors. If other behaviors do change with increasing physical activity, this would complicate interpretation of differences in study outcomes in exercise intervention trials. DESIGN: Randomized controlled trial. SETTING/PARTICIPANTS: 173 sedentary, overweight (body mass index between 24.0 and 25.0 kg/m2 with body fat>33% or BMI>or=25.0 kg/m2), postmenopausal women, ages 50 to 75 years, not using hormone therapy, and living in the Seattle, WA area. INTERVENTION: Participants were randomly assigned to an exercise intervention (n=87) or a stretching-control group (n=86). The exercise intervention included facility and home-based moderate-intensity exercise. MAIN OUTCOME MEASURES: Changes in dietary intake, alcohol consumption, and medication and supplement use were compared from baseline to 3- and 12-month follow-up between exercise and control groups, and by tertiles of exercise adherence. Data were collected between January 1998 and July 2001. RESULTS: In general, changes in dietary intake between the exercise and control group were not statistically different. The exercise group had a greater increase in the proportion of participants who used multivitamins (+5%) compared to the control group (-10%) at 3 months (p-interaction=0.04), but not at 12 months (p-interaction=0.58). Furthermore, there were few differences when comparing changes in health behaviors across exercise adherence tertiles. CONCLUSIONS: Our results suggest that participation in a year-long exercise intervention trial among post menopausal women has little effect on other health behaviors. These findings suggest that additional behavior changes in exercise trials are minimal and unlikely to bias primary study results. PMID- 17287150 TI - The medication Adherence and Blood Pressure Control (ABC) trial: a multi-site randomized controlled trial in a hypertensive, multi-cultural, economically disadvantaged population. AB - The Medication Adherence and BP Control Trial (ABC Trial) is a randomized, controlled, multi-site, medication adherence and blood pressure (BP) control trial in an economically disadvantaged and multi-cultural population of hypertensive patients followed in primary care practices. To date, no other such trial has been published in which objective measures of adherence (electronic pill bottles) were used to assess the effectiveness of these behavioral interventions for hypertension. This study tested a combination of commercially available interventions that can be easily accessed by health care providers and patients, and therefore may provide a real-world solution to the problem of non adherence among hypertensives. The aim of the ABC Trial was to test the effectiveness of a stepped care intervention in improving both medication adherence to an antihypertensive medication regimen and BP control. Step 1 of the intervention employed home Self-BP Monitoring (SBPM); at this stage, there were two arms: (1) Usual Care (UC) and (2) Intervention. At Step 2, patients in the intervention arm whose BP had not come under control after 3 months were further randomized to one of two conditions: (1) continuation of SBPM (alone) or (2) continuation of SBPM plus telephone-based nurse case management (SBPM+NCM). Electronic Medication Event Monitoring (MEMS) was the primary measure of medication adherence, and in-office BP was the primary measure of hypertension control. We present an overview of the study design, details of the administrative structure of the study and a description of clinical site recruitment, patient recruitment, and follow-up assessments. PMID- 17287151 TI - Implementation of electronic data capture systems: barriers and solutions. AB - Although increasing in pace, the conversion to Electronic Data Capture (EDC) has been a slow progression. The use of EDC systems should confer improved data integrity, cost savings and a shorter time to study database closure. This will reduce the time to market and cost of new medications. With the current sentiment of the industry suggesting the cost analysis has been accepted to be in favor of EDC, the likely limitation to disseminated use is an inability to implement these systems. If the leadership at the sponsor, clinical research organization and investigator site is cognizant of the barriers to implementation, they can anticipate and mitigate them prior to the users becoming disgruntled and resistant to the new method of data capture. Once understood, barriers such as user input, technical support, user motivation, regulatory requirements, communication with users, timing of implementation, software installation, graphical user interface, identification of bridgers, patient participation, availability of technology, and costs can be better addressed at the beginning of the implementation process and successfully averted. This review discusses these barriers and potential solutions that can assist the clinical trial industry in achieving more wide-spread EDC use and the resulting improvement in operating efficiencies. PMID- 17287152 TI - Identifying four Trypanosoma cruzi I isolate haplotypes from different geographic regions in Colombia. AB - Trypanosoma cruzi has been classified into the groups T. cruzi I and T. cruzi II. The latter is subdivided into five smaller lineages based on multilocus enzyme electrophoresis and random amplified polymorphic DNA, designated as IIa-IIe, which shows correspondence with rRNA/mini-exon lineages. Twelve previously characterised T. cruzi isolates from different hosts, including humans, Didelphis marsupialis, and triatomines were analysed to establish genetic variability in T. cruzi group T. cruzi I isolates from different geographical regions of Colombia. DNA samples were sequenced based on the mini-exon gene intergenic region. Sequences were analysed using Clustal W, Staden 1.5 and MEGA3 software, and using reported sequences from the GenBank as reference. The genetic distances were analysed using Kimura's two-parameter model. The isolates' joint alignment was of 350bp, and the calculated nucleotide divergence was of 17.5%. The differences consisted of 23 transitions (7.2%), 14 transversions (4.4%) and 19 insertion deletions (5.9%). The Colombian T cruzi I isolates revealed sufficient genetic variability for us to propose the existence of four haplotypes identified through single nucleotide polymorphism (SNP) and insertion/deletion found in the mini exon gene's non-transcribed spacer intergenic region. PMID- 17287153 TI - Aqueous micellar two-phase system composed of hyamine-type hydrophobically modified ethylene oxide and application for cytochrome P450 BM-3 separation. AB - The hydrophobically modified ethylene oxide polymer, HM-EO, was modified with an alkyl halide to prepare a hyamine-type HM-EO, named N-Me-HM-EO, which could be used for forming N-Me-HM-EO/buffer aqueous micellar two-phase system. The critical micelle concentration of N-Me-HM-EO solution and the phase diagrams of N Me-HM-EO/buffer systems were determined. By using this novel aqueous micellar two phase system, the separation of cytochrome P450 BM-3 from cell extract was explored. The partitioning behavior of P450 BM-3 in N-Me-HM-EO/buffer systems was measured. The influences of some factors such as total proteins concentration, pH, temperature and salt concentration, on the partitioning coefficients of P450 BM-3 were investigated. Since the micellar aggregates in the N-Me-HM-EO enriched phase were positively charged, it was possible to conduct the proteins with different charges to top or bottom phases by adjusting pH and salt concentration in the system. A separation scheme consisting of two consecutive aqueous two phase extraction steps was proposed: the first extraction with N-Me-HM-EO/buffer system at pH 8.0, and the second extraction in the same system at pH 6.0. The recovery of P450 BM-3 was 73.3% with the purification factor of 2.5. The results indicated that the aqueous micellar two-phase system composed of hyamine modified polysoap has a promising application for selective separation of biomolecules depending on the enhanced electrostatic interactions between micelles and proteins. PMID- 17287154 TI - Determination of mildronate in human plasma and urine by liquid chromatography tandem mass spectrometry. AB - A sensitive and selective analytical method based on liquid chromatography-triple quadrupole mass spectrometer has been developed to determine mildronate in human plasma and urine. The aim of this work was to find a valid method to study the pharmacokinetic profiles of mildronate in humans. Mildronate is a heart protection medicine, a carnitine's structural analogue, so levocarnitine was used as an internal standard for quantification. Under the electrospray ionization source positive ion mode, calibration curves with good linearities (r=0.9998 for plasma sample and r=0.9999 for urine sample) were obtained in the range of 1.0 20,000 ng ml(-1) for mildronate. The detection limit was 1 ng ml(-1). Recoveries were around 90% for the extraction from human plasma, and good precision and accuracy were achieved. This method is feasible for the evaluation of pharmacokinetic profiles of mildronate in humans, and to the best of our knowledge, this is the first report on LC-MS-MS analysis of mildronate in plasma and urine. PMID- 17287155 TI - Urban land rights and child nutritional status in Peru, 2004. AB - Advocates of land-titling programs in developing countries posit that these programs lead to a multitude of benefits, including health improvements. This paper presents the results of a child health survey of several Lima communities after various time exposures to Peru's urban land-titling program. The results provide suggestive evidence that improved property rights increase children's weight but not their height, which is consistent with previous work on the topic. However, titles also appear to raise children's risk of being overweight or obese, implying that the observed weight gain is not necessarily an improvement in nutritional status. PMID- 17287156 TI - Galactomannan antigen enzyme-linked immunosorbent assay for diagnosis of invasive aspergillosis after hematopoietic stem cell transplantation. AB - Invasive aspergillosis is difficult to diagnose in patients undergoing hematopoietic stem cell transplantation (HSCT). In 2003, a serum enzyme-linked immunosorbent assay (ELISA) test for the detection of galactomannan (a glycoprotein found on the Aspergillus cell wall) became available in the United States. In 2004, patients undergoing HSCT were screened biweekly with the galactomannan ELISA at our institution. We performed a retrospective chart review of 121 SCT patients who underwent galactomannan testing. Thirteen of the patients (10.7%) had at least 1 positive galactomannan ELISA, and 4 had multiple positive tests. When calculated in reference to a proved or probable diagnosis of aspergillosis, the galactomannan ELISA had a sensitivity of 0.50 and a specificity of 0.94. The positive predictive value was 0.46, and the negative predictive value was 0.94. Galactomannan ELISA had fewer false-positive and false negative results in pediatric patients than in adult patients. In 4 of the 12 cases of invasive aspergillosis, the galactomannan ELISA was positive before other microbiologic evidence of aspergillosis was available. In these cases, a positive ELISA predated culture and cytologic evidence of invasive aspergillosis by a mean of 5 days (range, 1-8 days). Our findings indicate that a biweekly serum galactomannan ELISA is a highly specific diagnostic tool for detecting invasive aspergillosis in patients undergoing HSCT. When used regularly, the ELISA may allow for earlier diagnosis of invasive aspergillosis in some patients. The test is troubled by a low sensitivity and high frequency of false-negative tests. PMID- 17287158 TI - Hepatoma-related gamma-glutamyl transferase in laboratory or clinical diagnosis of hepatocellular carcinoma. PMID- 17287159 TI - Liver graft preservation: an overview. AB - BACKGROUND: The quality of liver graft and outcome of liver transplantation is affected by the length of ischemia time during the donor operation. The retrieved graft may have a serious damage during the time of stoppage of the circulation in the donor until revascularization in the recipient. It is very important to develop a suitable preservation fluid to minimise the damage caused by the ischemic period and to make the surgical procedure semi-elective. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1960-2006) on liver preservation solution, liver transplantation, kidney transplantation and other related subjects. RESULTS: Since 1960 until 2006 many preservation solutions have been introduced. Most of them are based on the effect of hypothermia to minimise the metabolic pathway in the liver graft. In the earlier studies electrolyte solutions were used to perfuse the liver through the portal vein. The first modification in preservation solution was done by Collins who was able to extend the kidney preservation time up to 30 hours. In recent years, the introduction of University of Wisconsin (UW) preservation solution has made a revolution in the field of organ preservation. The UW solution is based on lactobionate and raffinose as impermeants to suppress hypothermic-induced tissue swelling, replacing glucose and mannitol in Collin's solution and hypertonic citrate respectively. Recently a research group in Kyoto University works to produce a more reliable preservation solution. They investigated the importance of saccharides and electrolytes in lung preservation and developed their original ET-Kyoto solution. However, more studies are still needed to evaluate the new ET Kyoto solution. CONCLUSIONS: The development of new preservation solutions represents a corner stone in the field of organ transplantation. In the future we might be able to extend the time of organ preservation from hours to days. PMID- 17287160 TI - Progress in pancreas transplantation and combined pancreas-kidney transplantation. AB - BACKGROUND: Pancreas transplantation (PT) has proved effective but it is associated with a high risk of surgical complications and technical failure. Duct management and venous drainage are identified as major issues. Improvements in immunosuppression and prophylaxis greatly have contributed to surgical progress. DATA SOURCES: A literature search of the PubMed database (1996-2005) was conducted and research articles on PT reviewed. RESULTS: More than 23 000 PTs have been performed throughout the world. The majority (83%) were performed in combination with kidney transplantation [simultaneous pancreas-kidney transplantation (SPK)]. Pancreas graft survival rates at one year were 85% for 2001-2003 SPK cases, 79% for pancreas after kidney transplantation (PAK) cases, and 76% for pancreas transplantation alone (PTA) cases. For the 1999-2003 cases, enteric drainage was done in 79% of the SPK cases and bladder drainage in 21%. Patient survival rates, pancreas and kidney graft survival rates, and pancreas graft immunological failure rates did not differ significantly in enteric versus bladder drainage cases. All the available data fail to demonstrate a definitive advantage of portal drainage over systemic drainage. From 1993 to 2002, the use of rabbit antithymocyte globulin increased from 0 to 37%; the use of daclizumab increased from 0 to 16%; and the use of basiliximab increased from 0 to 25%. In 1993, 98% of SPK recipients received cyclosporine; but this was decreased to 9% in 2002. Tacrolimus (FK506) usage has increased from 0 (1993) to 87% (2002) of SPK recipients. Sirolimus (SIR) usage has increased from 0 (1993) to 18% (2002) of SPK recipients. CONCLUSIONS: PT remains an effective therapy for treatment of type I diabetes mellitus. Enteric drainage is currently predominant in SPK, but bladder drainage is still largely used. Portal drainage is as safe as systemic drainage, but there is still no convincing evidence about whether it is immunologically or metabolically convenient. The combined of FK506 and mycophenolate mophetil (MMF) is the preferred maintenance immunosuppression in PT. Sirolimus may be a good alternative as a second agent in recipients of PT under FK506 therapy. PMID- 17287161 TI - Liver transplant for 70 patients with end-stage liver diseases. AB - BACKGROUND: Liver transplantation has evolved as a successful treatment for patients with end-stage liver cirrhosis and acute liver failure. Postoperative survival rates have increased to 90% in 1 year and 80% in 5 years as a result of improvements in immunosuppression, perioperative management and surgical techniques. However, a wide range of postoperative complications are of technical or medical origin. This study was undertaken to determine the relationship between the technical improvements and optimal timing of surgery and its outcome. METHODS: From April 1999 to October 2005, typical orthotopic or piggyback liver transplantation was performed in 70 patients (58 men and 12 women, aged 19-74 years). Twenty-four patients had liver carcinoma and cirrhosis, and 46 had benign liver disease. RESULTS: All patients survived the operation and 14 died in the first month after surgery because of respiratory failure (6), respiratory failure accompanied by acute renal failure (4), intra-abdominal hemorrhage and infection (2), and cerebral edema (2). A total of 76 complications occurred in the 70 patients after operation: pneumonia (34), right pleural effusion (11), bile leakage (7), postoperative intra-abdominal hemorrhage and infection (4), acute renal failure (4), acute rejection (3), wound infection (2), biliary tract stenosis (2), severe cholangitis derived from cholelith (2), morphological alteration of biliary tree (2), cerebral edema (2), empyema (1), chronic rejection (1), and wound hematoma (1). Finally, 33 patients survived more than 6 months, 16 more than 1 year, 4 more than 2 years, and 2 more than 6 years after operation. The perioperative survival rate was 80% in this series. CONCLUSIONS: Liver transplantation is an effective treatment for patients with end-stage liver disease. To obtain good results, improvements of surgical technique, optimal timing and better postoperative care are needed. PMID- 17287157 TI - Nonmyeloablative unrelated donor hematopoietic cell transplantation to treat patients with poor-risk, relapsed, or refractory multiple myeloma. AB - The purpose of this study was to determine long-term outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in patients with poor risk multiple myeloma. A total of 24 patients were enrolled; 17 patients (71%) had chemotherapy-refractory disease, and 14 (58%) experienced disease relapse or progression after previous autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43-135 days later with unrelated transplantation, whereas 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m(2)) and 2 Gy of total body irradiation before HLA-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced nonfatal graft rejection. The incidences of acute grades II and III and chronic graft-versus-host disease were 54%, 13%, and 75%, respectively. The 3-year nonrelapse mortality (NRM) was 21%. Complete responses were observed in 10 patients (42%); partial responses, in 4 (17%). At 3 years, overall survival (OS) and progression-free survival (PFS) rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior OS and PFS (77% and 51%) compared with patients proceeding directly to unrelated donor transplantation (44% and 11%) (PFS P value = .03). In summary, for patients with poor-risk, relapsed, or refractory multiple myeloma, cytoreductive autologous HCT followed by nonmyeloablative conditioning and unrelated HCT is an effective treatment approach, with low NRM, high complete remission rates, and prolonged disease-free survival. PMID- 17287162 TI - Endoscopic diagnosis and treatment of biliary leak in patients following liver transplantation: a prospective clinical study. AB - BACKGROUND: Orthotopic liver transplantation has been widely used in patients with end-stage liver disease within the last two decades. However, the prevalence of biliary complications after liver transplantation remains high. The most common short-term biliary complication may be biliary leak. So, we examined 13 patients with biliary leak after liver transplantation, attempting to evaluate the role of endoscopic diagnosis and treatment of biliary leak and the incidence of bile duct stricture after healing of the leak. METHODS: Six cases of T-tube leak and seven cases of anastomosis leak complicating liver transplantation were enrolled in this prospective study. Six patients were treated by endoscopic plastic stent placement, two by nasobiliary catheter drainage, two by papillosphincterotomy, and three by nasobiliary catheter drainage combined with plastic stent placement. Some patients received growth hormone treatment. RESULTS: The bile leak resolution time was 10-35 days in 10 patients with complete documentation. The median time of leak resolution was 15.3 days. Four cases of anastomosis stricture, three cases of common hepatic duct and one case of multiple bile duct stenosis were detected by follow-up nasobiliary catheter cholangiography or endoscopic retrograde cholangiopancreatography. CONCLUSIONS: Endoscopic nasobiliary catheter or plastic stent placement is a safe and effective treatment for bile duct stricture occurring after bile leak resolution in most liver transplantation patients. Nasobiliary catheter combined with plastic stent placement may be the best choice for treating bile leak, because, theoretically, it may prevent the serious condition resulting from accidental nasobiliary catheter dislocation, and it may have prophylactic effects on upcoming bile duct stricture, although this should be further confirmed. PMID- 17287163 TI - Infusion of donor hepatic non-parenchymal cells prolongs survival of skin allografts in mice: role of microchimerism and IL-4. AB - BACKGROUND: In the mouse skin allograft model, specific immune tolerance to the donor was induced by injection of donor hepatic non-parenchymal cells (NPCs). This markedly prolonged the survival time of the allograft. The mechanism of the induction of immune tolerance with donor hepatic NPCs is thought to be related to microchimerism and the IL-4 level. This work aimed at exploring the way of inducing immune tolerance and understanding the mechanism. METHODS: C57BL/6 (B6) mice were primed by intravenous injection of 2 x 10(7) NPCs from C3H mice. Cyclophosphamide (200 mg/kg) was injected intraperitoneally 48 hours later. Eighteen days after the NPC injection, skin from C3H mice was transplanted to B6 mice and the survival of the grafts was assessed. The immune reaction of splenocytes from the treated B6 mice to donor-specific T-cells was measured by 3H TdR incorporation. Microchimerism in the spleen was determined by flow cytometric analysis sytem (FCAS) analysis, and the serum level of IL-4 was assayed by ELISA at designed times. RESULTS: The survival time of the skin graft was markedly prolonged from 10 days to 70 days in controls. Microchimerism in the spleen was found as early as day 1 post-NPC injection, then it increased steadily, and there was a positive relationship between graft survival and the quantity of microchimerism. The ELISA results showed that NPC infusion enhanced IL-4 production, especially in the mice with longer graft survival. CONCLUSION: Donor NPC infusion pre-transplant can prolong the survival of the skin graft and microchimerism and high levels of IL-4 may be involved. PMID- 17287164 TI - Detection of hepatitis E virus RNA in sera of patients with hepatitis E by polymerase chain reaction. AB - BACKGROUND: The duration of viremia during hepatitis E virus (HEV) infection has rarely been reported. This study was undertaken to detect HEV RNA in sera of patients with hepatitis E and to understand the process of HEV infection more thoroughly. METHODS: HEV RNA was detected in the serum samples of hospitalized patients with acute hepatitis E by reverse transcriptase-nested polymerase chain reaction (RT-nPCR) using two pairs of primers from open reading frame (ORF) 1 of the HEV genome. RESULTS: The serum samples from 44 (70%) of 62 patients were positive for HEV RNA. Thirty-two of these patients, with 288 serial serum specimens, were followed up for the whole process, and 24 patients (75%) were positive for HEV RNA. The positive rates declined with the course of the disease, serum HEV RNA persisting for 20.6 days on average after onset of illness. Serum HEV RNA remained positive in 36 (81.8%) of the 44 patients at the time their alanine aminotransferase (ALT) began to decrease. There was no difference in HEV RNA positivity between serum with high levels of HEV antibody (peak P/N ratio > or =4.0) and that with low levels (peak P/N ratio <4.0), with 25 out of 35 and 19 out of 27 (71.4% vs. 70.4%, P>0.05), respectively. CONCLUSIONS: There is a relatively long period of HEV viremia in patients with hepatitis E. The proportion of HEV viremia and its duration are not directly related to serum ALT values or HEV antibody levels. PMID- 17287165 TI - Autologous transfusion with modified total hepatic vascular exclusion for extracapsular resection of giant hepatic cavernous hemangioma. AB - BACKGROUND: This paper was to review the effects of intraoperative autologous transfusion during modified, normal-temperature, total hepatic vascular exclusion (THVE) for extracapsular resection of giant hepatic cavernous hemangioma. METHODS: The clinical data from 28 patients, who underwent hepatic resection requiring intraoperative autologous transfusion with the cell-saver apparatus, were analyzed retrospectively. The tumors in the 28 patients involved the proximal hepatic veins and inferior vena cava. The volume of these hemangiomas ranged from 12 x 15 cm to 18 x 40 cm. All patients had varying degrees of THVE. RESULTS: The 28 patients with hemangioma received integrated resection and recovered. One patient had rupture of tumors resulting in massive hemorrhage of 6000 ml during liver resection; 4 patients had blood transfusions of 400-800 ml; the other 23 patients had no blood transfusion. Only 6 patients underwent the Pringle maneuver with resection. The other 22 patients underwent THVE during the liver resection. The interval of THVE was 5-30 minutes (mean 16 minutes). CONCLUSIONS: Intraoperative autologous transfusion during modified, normal temperature THVE for extracapsular resection of huge hepatic cavemous hemangioma is feasible. PMID- 17287166 TI - Ruptured hepatocellular carcinoma following chemoembolization: a western experience. AB - BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a recommended first line therapy for unresectable hepatocellular carcinoma (HCC). Serious complications such as neutropenic sepsis and hepatic decompensation are well known, but rupture of HCC following TACE is a rare and potentially fatal complication. The aim of this study was to identify the incidence of ruptured HCC following TACE and the associated risk factors. METHODS: A retrospective analysis was performed using our liver database with key words "chemoembolization", "ruptured HCC" covering the patients who received chemoembolization from January 1995 to December 2005. There were no exclusions. RESULTS: A total of 294 patients received chemoembolization in 530 sessions during the 10-year period. Of these, 2 ruptured following treatment (incidence 0.68%). The mean age was 65 years and the interval between the treatment and rupture was 2 and 24 days. The common factors were male sex, large tumor size (range 11-13 cm), and exophytic tumor growth. One patient died 2 days after rupture with hepatic decompensation while the second is alive after a 6-month follow up without tumor recurrence. CONCLUSIONS: Ruptured HCC following TACE is a rare but serious complication. Large tumor size, male sex, and exophytic growth of tumor may be predisposing factors for rupture. PMID- 17287167 TI - Focal nodular hyperplasia of the liver in 86 patients. AB - BACKGROUND: Focal nodular hyperplasia (FNH), the second most common benign hepatic tumor after hemangioma, is characterized by a stellate central scar and hyperplastic nodules. Although some large FNH may be associated with significant symptoms, more frequently they are discovered incidentally on physical examination or the work-up of unrelated symptoms. Since its nature and pathogenesis are still controversial, accurate diagnosis of FNH based on clinical presentation and radiographic studies is difficult. The purpose of this study was to explore the diagnosis and treatment of FNH. METHODS: Eighty-six FNH patients confirmed pathologically were treated at the Liver Cancer Institute in our hospital from 1996 to 2006. Their clinical manifestations, imaging presentation, pathological findings, and surgical results were analyzed retrospectively. RESULTS: Of the 86 patients with 99 foci, 54 were male and 32 female, with a mean age of 37 years. Eighty patients had a single solitary focus and 6 had multiple foci. Tumor diameter was less than 5 cm in 69 patients, 5-10 cm in 15, and more than 10 cm in 2. The overall rate of correct preoperative diagnosis was 59.3% (51/86) including 32.9% (26/79) by color Doppler flow imaging (CDFI), 60.3% (35/58) by CT, and 77.4% (24/31) by MRI. All the 86 patients underwent resection with good curative effect. CONCLUSIONS: CT and MRI are important diagnostic methods for FNH but it is difficult to make a definite preoperative diagnosis for partial classical and all non-classical FNH patients. We suggest that patients with clinical symptoms or with indefinite diagnosis should accept surgical removal. PMID- 17287168 TI - Factors related to pleural effusion following hepatectomy for primary liver cancer. AB - BACKGROUND: Pleural effusion frequently complicates hepatectomy and multiple factors contribute to its development following hepatectomy for primary liver cancer. The purpose of this study was to evaluate these factors. METHODS: From March 2003 to May 2005, 228 consecutive patients with primary liver cancer underwent hepatectomy in our department were evaluated retrospectively to identify factors related to postoperative pleural effusion. RESULTS: Among the 228 patients, postoperative pleural effusions arose in 58 (25.4%). Univariate analysis showed significant differences in postoperative ascites, subphrenic collection, Pringle manoeuvre length, drainage amount on postoperative day 1, albumin level on postoperative day 7, alanine aminotransferase (ALT) level on postoperative days 1 and 3, prealbumin level on postoperative days 3 and 7, and tumor size (P<0.05). Ordinal regression analysis revealed that subphrenic collection, drainage on postoperative day 1 and ALT plus prealbumin on postoperative days 1 and 3 were statistically significantly related to postoperative pleural effusion (P<0.05). CONCLUSION: Subphrenic collection and operative injury to the liver appeared to be significantly related to pleural effusion after hepatectomy for primary liver cancer. PMID- 17287169 TI - Predominant expression of Th1-type cytokines in primary hepatic cancer and adjacent liver tissues. AB - BACKGROUND: Research has revealed a shift towards Th2 in many types of malignant tumor, but the state of Th1/Th2 is not clear in patients with primary hepatic cancer (PHC). This study was designed to determine the expression of Th1- versus Th2-type cytokines in primary hepatic cancer and the adjacent liver tissue in order to provide evidence for treatment of the Th1/Th2 shift. METHODS: Samples were collected from 11 patients with PHC. The gene expression of Th1/Th2 cytokines was detected by reverse transcriptase polymerase chain reaction (RT PCR) using IFN-gamma and IL-2 as Th1-type cytokine genes, and IL-4 and IL-10 as Th2-type cytokine genes. RESULTS: Th1-type cytokines were expressed in 7/11 PHCs and 9/11 adjacent liver tissues, while Th0 type cytokines occurred in 4/11 PHCs and 2/11 adjacent liver tissues. CONCLUSION: Th1-type cytokines are expressed predominantly in primary hepatic cancer and the adjacent liver tissue. PMID- 17287170 TI - Recurrent lithiasis after surgical treatment of elderly patients with choledocholithiasis. AB - BACKGROUND: The recurrence rates of choledocholithiasis depend on the type of the disease. This study was undertaken to examine recurrent lithiasis after surgical treatment of elderly patients with choledocholithiasis, especially with primary common bile duct stones, and thereby to determine the best treatment modality for choledocholithiasis in the elderly. METHODS: The recurrence rates of choledocholithiasis were calculated from the records of 193 outpatients who had been treated from January 1993 to January 2005 and monitored for periods ranging from 1 to 12 years (mean 6.7 years). The patients were divided into 3 groups: 81 who had undergone choledocholithotomy and T-tube drainage, 41 who had had choledochoduodenostomy, and 71 patients who had received choledochojejunostomy. RESULTS: Since the 41 choledochoduodenostomy cases had only one recurrence of choledocholithiasis, the recurrence rate was analyzed for the remaining 152 cases, which were divided into two groups: group A with recurrent lithiasis (13 cases), and group B without recurrence (139 cases). The recurrence was found in 7 patients after choledocholithotomy and T-tube drainage (7/81, 8.6%), and in 6 patients after choledochojejunostomy (6/71, 8.5%). The recurrence rates for these procedures were higher than for choledochoduodenostomy (1/41, 2.4%, P<0.05). Moreover, stones recurred in 4 of the 11 patients with primary bile duct stones who underwent choledocholithotomy and T-tube drainage (4/11, 36.4%), and in 5 of the 34 patients who had choledochojejunostomy (5/34, 14.7%). The recurrence rates for these procedures were higher than for choledochoduodenostomy (1/39, 2.6%, P<0.05). The diameter of the common bile duct was more dilated in group A (14.6+/ 3.9 mm) than in group B (10.8+/-4.5 mm, P<0.05). Primary bile duct stones were found in 9 cases of group A (69.2%), and in 36 cases of group B (25.9%, P<0.01). CONCLUSION: Choledochoduodenostomy should be recommended for elderly patients with primary bile duct stones to prevent postoperative recurrent lithiasis. PMID- 17287171 TI - Inhibitory effect of norcantharidin on the growth of human gallbladder carcinoma GBC-SD cells in vitro. AB - BACKGROUND: Gallbladder carcinoma is a lethal malignant neoplasm with dismal surgical results. Unfortunately, the adjuvant therapies for gallbladder carcinoma such as chemotherapy and radiotherapy are also disappointing. We reported that norcantharidin (NCTD), a demethylated form of cantharidin, which is an active ingredient of the Chinese medicine Mylabris, was used against human gallbladder carcinoma GBC-SD cells. In the present study, we further studied the mechanism underlying the inhibitory effect of NCTD on growth of human gallbladder carcinoma GBC-SD cells in vitro. METHODS: Human gallbladder carcinoma GBC-SD cells were grown in cell culture and divided into a NCTD group and a control group. The inhibitory effect of NCTD on growth of GBC-SD cells was investigated by evaluation of proliferation, cell cycle, apoptosis and morphological changes of the cells. Cell proliferation was assessed by tetrazolium-based colorimetric assay. The induction of cell cycle arrest and apoptosis was measured by flow cytometry. The morphological changes of the cells were observed by light- and electron-microscopy. To elucidate the anticancer mechanism of NCTD, expression of the proliferation-related gene proteins PCNA, Ki-67, cyclin-D1 and p27 and the apoptosis-related gene proteins Bcl-2, Bax and Survivin were determined by the streptavidin-biotin complex method and RT-PCR. RESULTS: NCTD inhibited the proliferation of GBC-SD cells in a dose- and time-dependent manner, with an IC50 of 56.18 microg/ml at 48 hours. The flow cytometric profiles revealed that NCTD (at the IC50 for 48 hours) significantly increased the proportion of cells in G2/M phase and significantly decreased the proportion of cells in S phase, with a significantly increased rate of cell apoptosis. After treatment with the 48-hour IC50 dose of NCTD, cell shrinkage, vacuolar cytoplasm, membrane budding, karyorrhexis, karyolysis, chromosome condensation and chromatin aggregation in some GBC-SD cells were observed by light-microscopy; decreased microvilli, Golgiosome atrophy, mitochondrial swelling, nuclear shrinkage, chromosome condensation and typical apoptosis bodies were seen by electron-microscopy, and the morphological changes of apoptosis occurred in GBC-SD cells. The expression of PCNA, Ki-67 and Bcl-2 proteins decreased significantly; the Pix or relative levels of PCNA mRNA, cyclin-D1 mRNA, Bcl-2 mRNA and Survivin mRNA decreased significantly, whereas the Pix or relative levels of p27 mRNA and Bax mRNA increased significantly. CONCLUSIONS: NCTD inhibits the growth of human gallbladder carcinoma GBC-SD cells in vitro. Its anticancer mechanism may correlate with inhibition of cell proliferation, arrest of the cell cycle, blockage of DNA synthesis, influence on cell metabolism, induction of cell apoptosis and influence on expression of the proliferation-related genes PCNA, Ki 67, cyclin-D1 and p27, and the apoptosis-related genes Bcl-2, Bax and Survivin in human gallbladder carcinoma GBC-SD cells. PMID- 17287172 TI - Distribution of natural killer cells and T-lymphocyte subsets in peripheral blood, gallbladder cancer and surrounding tissue. AB - BACKGROUND: The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to define the relationship between the immune function of local cells and cancer development by investigating the distribution of natural killer (NK) cells and T-lymphocyte subsets in peripheral blood, the cancer tissue and the tissue surrounding gallbladder carcinoma. METHODS: The numbers of CD4+ and CD8+ T-lymphocytes and NK cells were measured by flow cytometry in samples taken from gallbladder cancer tissue, the surrounding tissues and peripheral blood of 38 patients, and compared with the numbers in the peripheral blood and gallbladder tissue of 30 patients with cholecystitis as controls. RESULTS: The numbers of CD4+ and CD8+ T-cells and NK cells in gallbladder cancer tissues were significantly higher than those in the surrounding tissue and gallbladder with gallstone. However, the ratio of CD4+/CD8+ was lower in the cancer tissue than that in the surrounding tissue and tissue from gallbladders with gallstones. The distribution of CD4+ and CD8+ T cells and NK cells in mucous membrane of cholecystitis gallbladder and that in the tissue surrounding gallbladder cancer were significantly different. CONCLUSIONS: Disproportionate and imbalanced distribution of NK cells and subsets of T-lymphocytes occurs in the mucous membrane proper of gallbladder cancer and surrounding tissue. Although gallbladder cancer tissue has higher expressions of CD4+, CD8+ and NK cells, the immune function is low or in an inhibited state. In gallbladder cancer immunization therapy, local cellular immunological function should be enhanced and the protective barrier improved. PMID- 17287173 TI - Improved early diagnosis of cystadenocarcinoma of the pancreas. AB - BACKGROUND: Cystadenocarcinoma of the pancreas is insensitive to radiotherapy and chemotherapy, and surgery is at present the definitive treatment. Early and accurate diagnosis of cystadenocarcinoma is crucial for increasing the five-year survival rate and the resectable rate. There is no definitive and effective method of early diagnosis of cystadenocarcinoma of the pancreas in China and other countries. METHODS: We compared endoscopic ultrasonography-guided (EUS guided) fine needle aspiration biopsy combined with cyst fluid carcinoembryonic antigen (CEA), CA19-9 examination with computed tomography (CT), B ultrasonography (B-US) and serum CEA and CA19-9, to explore methods of early diagnosis of cystadenocarcinoma of the pancreas. Retrospective analysis was made on the clinical data of 126 cases of benign pancreatic lesion (90 cases) and cystadenocarcinoma (36). RESULTS: The sensitivity of B-US and CT for cystadeno carcinoma was 52.8% and 77.8%, while the specificity was 78.9% and 86.7%, respectively. When measurement of CEA and CA19-9 of cyst fluid was combined with EUS-guided fine needle aspiration biopsy, the sensitivity was 94.4%, higher than that of B-US and CT (P<0.05). The sensitivity of cyst fluid CEA, CA19-9 examinations was considerably higher than that of serum CEA, CA19-9 (P<0.05). Upper gastrointestinal barium meal and endoscopic retrograde cholangiopancreatography (ERCP) had low sensitivity and specificity. CONCLUSIONS: EUS-guided fine needle aspiration biopsy combined with examination of cyst fluid CEA, CA19-9 is a credible means for early diagnosis of cystadenocarcinoma of the pancreas. B-US, CT and serum CEA, CA19-9 measurements are in common use, their findings are also very important. PMID- 17287174 TI - Detection of tumor stem cell markers in pancreatic carcinoma cell lines. AB - BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real-time RT PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non-pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels. CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments. PMID- 17287175 TI - A successful pregnancy following liver transplantation. AB - BACKGROUND: The safety and possibility of pregnancy following liver transplantation has been the hot topic in transplant. A case is reported with a review of the literature. METHOD: The data of a 22-year-old pregnant patient with end-stage liver disease who had undergone orthotopic liver transplantation in September 28, 2000 were analyzed retrospectively. RESULTS: After surgery, the patient was uneventfully recovered and was pregnant at the time of the 33rd month postoperation. The patient experienced a rejection on the 8th week of pregnancy and was successfully treated at this hospital. The patient was closely monitored throughout her pregnancy, and received routine antenatal care with respect to sonographic screening. Caesarean section was performed in March 18, 2004, and a health live-born infant weighing 2000 g was delivered at full-term. After the delivery, the patient was satisfactory with her health and the baby was healthy. CONCLUSION: Under close monitoring, successful pregnancy following liver transplantation is possible and safe in women with end-stage liver diseases. PMID- 17287176 TI - Giant mucinous biliary cystadenoma: a case report. AB - BACKGROUND: Biliary cystadenoma is a very rare cystic neoplasm of the liver. Its clinical features, diagnosis, pathologic characteristics, and optimal surgical management have not been defined clearly. In this article we describe the details of this rare disease. METHODS: A 40-year-old woman with a mass of the liver was verified by ultrasonography and LT. Ultrasonography showed a mixed echo of 18.4 cm x 14.72 cm x 15.54 cm in the left lobe of the liver. CT showed a vesicula of 19.9 cm x 13.5 cm in the right epigastrium, with a low density, clear edge, uneven density, and calcified shadow. The patient received successfully a left hepatectomy. Laboratory examination showed an elevation of CA125 to 62.62 U/ml and CA199>1000 U/ml. RESULTS: After the left hepatectomy, the patient was fully recovered. Her biliary cystadenoma was characterized by specific histological findings. During operation, a large cystic lesion was seen in the left hepatic lobe; its surface was dark red with abundant blood supply. Gross examination showed that the tumor almost occupied. The whole left lobe with a small amount of normal liver tissue close to the deltoid ligament. Pathologically, additional lobulated spaces were seen in the tumor with a lot of mucusa. The interior wall was lined with bile duct tissue, indicating a benign mucinous biliary cystadenoma. CONCLUSIONS: Ultrasonography and CT are the major methods for the diagnosis of mucinous biliary cystadenoma liver. Operation is the best way of treatment. PMID- 17287177 TI - Pancreaticoduodenectomy in the elderly over 80 years: a case report. AB - BACKGROUND: An increasing number of elderly patients have been considered for major surgical procedures, such as pancreaticoduodenectomy. The decision to recommend this operation for localized pancreatic cancer or other periampullary process in a very elderly patient is complicated by the frailty of the patient and the poor prognosis of the disease. Moreover, increased surgical experience associated with better patient selection may reduce the mortality rate, even in very elderly patients (over 80 years of age), after pancreaticoduodenectomy. METHODS: An 84-year-old woman underwent pancreaticoduodenectomy for ampullary adenocarcinoma. The tumor was classified pT3N0M0. RESULT: A good postoperative outcome was obtained. The patient is still alive, 18 months after operation. CONCLUSIONS: Radical resection of periampullary tumors is safe in selected patients of advanced age, with morbidity and mortality rates approaching those observed in younger patients. Age alone should not be a contraindication for pancreatic resection. PMID- 17287178 TI - Bile duct hamartomas--the von Meyenburg complex. AB - Hamartomas of the bile duct (von Meyenburg complex) are benign neoplasms of the liver, constituted histologically cystic dilatations of the bile duct, encompassed by fibrous stroma. We report a 42-year-old female patient with symptomatic cholecystitis, whose gross and ultrasonic appearance suggestive of multiple liver metastases. Magnetic resonance imaging and liver biopsy are the gold standards for diagnosis of this rare hepatobiliary condition. PMID- 17287179 TI - Social common mole-rats enhance outbreeding via extra-pair mating. AB - Females in many species engage in matings with males that are not their social mates. These matings are predicted to increase offspring heterozygosity and fitness, and thereby prevent the deleterious effects of inbreeding. We tested this hypothesis in a cooperative breeding mammal, the common mole-rat Cryptomys hottentotus hottentotus. Laboratory-based studies suggested a system of strict social monogamy, while recent molecular studies indicate extensive extra-pair paternity despite colonies being founded by an outbred pair. Our data show that extra-pair and within-colony breeding males differed significantly in relatedness to breeding females, suggesting that females may gain genetic benefits from breeding with non-resident males. Extra-colony male mating success was not based on heterozygosity criteria at microsatellite loci; however, litters sired by extra-colony males exhibited increased heterozygosity. While we do not have the data that refute a relationship between individual levels of inbreeding (Hs) and fitness, we propose that a combination of both male and female factors most likely explain the adaptive significance of extra-pair mating whereby common mole rats maximize offspring fitness by detecting genetic compatibility with extra pair mates at other key loci, but it is not known which sex controls these matings. PMID- 17287180 TI - Early learning influences species assortative mating preferences in Lake Victoria cichlid fish. AB - The Lake Victoria 'species flock' of cichlids is puzzling because reproductive isolation often occurs in the absence of substantial ecological differences among species. Theory predicts that this cannot evolve with most genetic mechanisms for mate choice. We provide the first evidence that learning, in the form of sexual imprinting, helps maintain reproductive isolation among closely related cichlid species. Using a cross-fostering experiment, we show that young females develop a sexual preference for males of their foster mothers' species, even reversing species assortative mating preferences. We suggest that learning creates favourable conditions for reproductive isolation to evolve. PMID- 17287181 TI - Is there the potential for an epidemic of variant Creutzfeldt-Jakob disease via blood transfusion in the UK? AB - The discovery of three individuals suspected to have contracted variant Creutzfeldt-Jakob disease (vCJD) through blood transfusions has heightened concerns that a secondary epidemic via human-to-human transmission could occur in the UK. The Department of Health responded immediately to this threat by banning those who had received blood transfusions since 1980 from donating blood. In this paper, we conduct a sensitivity analysis to explore the potential size of a blood borne vCJD epidemic and investigate the effectiveness of public health interventions. A mathematical model was developed together with an expression for the basic reproduction number (R0). The sensitivity of model predictions to unknown parameters determining the transmission of vCJD via infected blood was assessed under pessimistic modelling assumptions. We found that the size of the epidemic (up until 2080) was bounded above by 900 cases, with self-sustaining epidemics (R0>1) also possible; but the scenarios under which such epidemics could arise were found to be biologically implausible. Under optimistic assumptions, public health interventions reduced the upper bound to 250 and further still when only biologically plausible scenarios were considered. Our results support the belief that scenarios leading to large or self-sustaining epidemics are possible but unlikely, and that public health interventions were effective. PMID- 17287184 TI - Shifting Ground(s): Surveying the contested terrain of LGBT studies and queer theory. AB - While queer theory initially grew out of lesbian, gay, bisexual, and transgender (LGBT) studies, there are numerous points of contestation between these two approaches, originating mostly from their disparate positions on (sexual) identity politics. To describe, analyze, and contextualize this contested terrain, we begin this piece by providing some historical notes on LGBT studies and queer theory. Next, we turn to an explication of some enduring tensions to identify the criticisms generated by LGBT scholars toward queer theory approaches and vice versa. What follows is our rationale for producing LGBT Studies and Queer Theory: New Conflicts, Collaborations, and Contested Terrain. In this section we discuss how this project originated and the specific objectives we hope this volume will meet. The contributions of the individual articles in this volume are identified and summarized next. Finally, in the context of LGBT studies' and queer theory's similar qualities and points of difference, we offer ideas for potential directions of scholarship in the future that would explore three major areas: identity and difference; community and community organizing; and political engagement and social change. PMID- 17287185 TI - Queer theory, late capitalism, and internalized homophobia. AB - The emergence of queer theory represents a transformation in the approach to lesbian, gay, bisexual and transgendered peoples. It has claimed new ground for treating sexuality and gender as worthy subjects in their own rights, rather than offshoots of gay and lesbian studies or of general cultural theory. The author contends, however, that it is doubtful that this approach can lead to social change. Queer theory has dismissed the usefulness of the disciplines that were the foundation of the social movements that initiated gay and lesbian studies, such as political economy, and in doing so, it has surreptitiously mirrored the social relations of reproduction that constitute late capitalism. This mirroring has had unseen consequences for the individual in society, and with queer theory's insistence on the relativity of experience and the dismissal of identity, has set the stage for a benign reinforcement of internalized homophobia. The author argues that this approach can be mediated by recognizing that identity is fluid, and that by focusing on identifying with social movements rather than centering analyses on the problems associated with identifying as a particular category of status and being, we can refocus our energies on the building and maintenance of mutual support and collective recognition that can lead to resolving the stagnation now dominating attempts to develop coalitions around issues that matter. PMID- 17287186 TI - Anti-homosexual prejudice . . . as opposed to what? Queer theory and the social psychology of anti-homosexual attitudes. AB - This article uses Sedgwick's distinction between minoritizing and universalizing theories of sexuality to analyze variability in social psychologists' studies of anti-homosexual prejudice, focusing on studies of attitudes. Anti-homosexual prejudice was initially defined in conversation with gay liberationists and presumed, among other things, that fear of homoerotic potential was present in all persons. Later social psychologists theorized anti-homosexual prejudice in strict minoritizing terms: as prejudice towards a distinct out-group. In the first section of this paper we discuss corresponding shifts in the conceptualization of anti-homosexual attitudes. Next, using a universalizing framework, we re-interpret experiments on behavioral aspects of anti-homosexual attitudes which were originally conceptualized using a minoritizing framework, and suggest avenues for future research. Finally, we examine how queer theory might enrich this area of social psychological inquiry by challenging assumptions about the politics of doing scientific work and the utility of identity-based sexual politics. PMID- 17287188 TI - A queer anxiety: assimilation politics and cinematic hedonics in Relax . . . It's Just Sex. AB - This essay explores the commodification of queer identities in independent cinema, offering particular attention to P. J. Castellaneta's 1998 film, Relax . . . It's Just Sex. Like many contemporary queer independent productions, Relax is ensnared in a representational cinematic hedonics, aspiring to sustain a traditional gay and lesbian politics and simultaneously produce pleasure for multiple audiences. While Relax attempts to position itself as a queer film that resists normative conceptions of sexuality, the feature inadvertently appropriates more essentialized understandings of identity closely aligned to liberation rhetoric. PMID- 17287187 TI - Outlaws or in-laws? Queer theory, LGBT studies, and religious studies. AB - Many queer theorists, like many queer activists and perhaps many LGBT people in general, regard religion as so inimical to their purposes and lives that it is not even worthy of critique; references to religion in queer theory, queer studies, and even LGBT studies are usually sparse, brief, and generally derogatory. Likewise, within most of the field of religious studies, queerness is rarely an issue of concern or even consciousness except in the context of organizational tensions over the proper roles of "homosexuals." While there is a growing body of work that brings these two fields together, the study of religion seems to be adapting only haltingly and partially to contemporary developments inLGBTstudies and queer theory. This essay assesses the current state of the "proto-fields" of LGBT studies and queer studies in religion, offers suggestions for new directions in the future, and considers the potential benefits of the interaction of these fields. PMID- 17287189 TI - Historicizing (bi)sexuality: a rejoinder for gay/lesbian studies, feminism, and queer theory. AB - One of the principal aims of queer theory has been to challenge heteronormative constructions of sexuality and to work the hetero/homosexual structure to the point of critical collapse. Despite an epistemic location within this very structure, however, the category of bisexuality has been largely marginalized and even erased from the deconstructive field of queer theory. This article explores some of the factors behind this treatment of bisexuality and suggests that bisexuality's marginalization and erasure brings into relief the strained relationship between the fields of gay/lesbian history, feminism, and queer theory. In exploring some early influential queer deconstructionist texts, it argues that in overlooking the role the category of bisexuality has played in the formation of the hetero/homosexual structure, the project of queer deconstruction has in important ways fallen short of its goals. The author concludes with a call to rethink conventional deconstructive reading practices. PMID- 17287190 TI - Troubling the canon: bisexuality and queer theory. AB - This essay explores the notion that bisexuality and contemporary bisexual political movements both align and trouble canons of queer theories of sexuality and gender. This project provides an historical review and assessment of recent bisexual theorizing to highlight key themes in its evolution as well as a discussion of how these themes have shaped the relationship of bisexuality and queer theory. Drawing on this assessment and a wider discussion of GLBT scholarship, we invite critical inquiry regarding the implications of bisexual theorizing on queer theory and vice versa. We address questions of bisexual epistemologies, its discursive roles within queer theory, and its impact on queer politics and organizing. Noting bisexuality's absence in much of this research and scholarship, we suggest these projects have been limited in their ability to fully and effectively address sexual subjectivity both in theory and in its everyday lived experience. PMID- 17287191 TI - Cape queer? A case study of Provincetown, Massachusetts. AB - Cape Queer is a case study that details how sexuality intersects with race, gender, and class in the development of the gay and lesbian resort community, Provincetown, Massachusetts. It asks scholars to pay closer attention to the ways in which methodologies and practices utilizing LGBT studies and queer theory can combine rather than separate to interrogate LGBT and queer histories, politics and communities. In the process, it assesses how the global mechanics of capitalism led to the local queering and eventually un-queering of a gentrified, white, gay and lesbian enclave. PMID- 17287193 TI - Desiring mates. AB - The discourse of gay liberation reads silence surrounding personal participation in same-sex sexualized pleasures as a sign of repression, oppression and a positioning in the closet. In contrast, coming out is an important step towards accepting one's true homosexual self. The demand for the emancipation of the homosexual type further suggests that all same-sex sexualized contact signifies the homosexuality of the subjects involved, regardless of whether they recognize this or not. This compulsory homosexualization of men who have sexualized contact with men does not apply to relationships between male friends ("mates"). A "mateship" union grants a level of privacy otherwise eradicated by a gay liberation movement insistent on the public confession of a homosexual orientation. To remain silent about corporeal pleasures poses a threat to the modernist preference for control of bodies and to the established gay identity. Silence offers a space for the construction of new modes of same-sex intimate relationships within a queer framework. PMID- 17287192 TI - Jewish disappearing acts and the construction of gender. AB - In this essay I propose to investigate the interarticulation of race/ethnicity and gender at two fin de siecle moments: the conceptualization of the Oedipus complex at the turn of the twentieth century and the conceptualization of gender as performative in contemporary queer theory. Though these gender constructions contrast strikingly with one another-queer theory opposes and calls into question the heteronormativity of the Oedipal itinerary-both theories are produced through the displacement of racial/ethnic difference onto sexual and gender difference. One line of investigation in this essay is to relate their difference to the distinct situations of ethnic in-betweenness in which they were produced. Freud's situation as a Jew undergoing assimilation to Western European customs has been compared to that of the post-colonial subject. Judith Butler's and Eve Kosofsky Sedgwick's theories of queer performativity have been located in a post assimilationist situation in the U.S. of the 1990s. At both moments a doubling takes place but with a radical shift in perspective. Whereas the post-colonial subject undergoes a psychic splitting in which the point of view of the colonizer predominates and promotes assimilation via mimicry, the post-assimilation subject performatively constructs difference, often by a reverse mimicry that involves identification with a subaltern group. Finally, in both situations the notion of "queer incoherence" is deployed not to negate gay and lesbian specificity, but rather to articulate such specificity as historically emergent, on the verge of definition. PMID- 17287194 TI - Teaching queer theory at a Normal School. AB - This article presents a case study of the ongoing struggle to queer West Chester University at the level of the institution, the curriculum, and the classroom. Part of that struggle includes an effort to establish a policy for free speech that accommodates the values of the institution toward diversity. Another part involves attempts to introduce LGBT Studies into the curriculum, and the resulting debates over whether the curriculum should be "gayer" or "queerer." I discuss the personal struggle to destabilize ready-made categories and encourage non-binary thinking, while honoring the identities we live, and perform, in the classroom. In the last four years, WCU has hired half a dozen out gay or lesbian faculty members, some of whom identify as "queer." In many ways, those faculty members have entered a climate open to new ideas for adding LGBT content to the curriculum and to queering the structure and curriculum of the university. But as faculty, staff, and students engage this cause-along with the broader cause of social justice at the University- we have found that our enemies are often closer than we might have guessed. Detailing the tensions that have characterized the landscape at WCUduring my three years and half years there, this essay elaborates on the epistemological and pedagogical issues that arise when queer Theory meets LGBT Studies in the process of institutional, curricular, and pedagogical reform. I argue that questions about content and method, inclusion and exclusion, and identity and performance can be answered only with a concerted effort and continued attention to the cultural tendency to re-assert binaries while simultaneously learning from them. What is true of West Chester, I argue, is true of the larger social system where the contested terrain of the queer has implications for the choices we make as both stakeholders and deviants in the systems we chronicle and critique. PMID- 17287195 TI - Containing uncertainty: sexual values and citizenship. AB - This essay reflects on one dimension of the challenge of being a queer ethicist. Can we have norms/values without liberal assumptions that might undo the important contributions of queer theory? The reemergence of appeals to "citizenship" in lbgt and queer debates serves as illustrations of this question. Reading Weeks's Invented Moralities: Sexual Values in an Age of Uncertainty(1995), while considering various scholars who have engaged the issue of sexual citizenship since, enables me to illustrate some of the issues that emerge around ethics and queerness at this particular moment. My argument is that attempts to offer constructive ethical engagement in the end often contain challenges rather than successfully address them. Critically examining Weeks's intervention into what he sees as our "loss" of moral authority and ethical concerns to the right wing is helpful for queer ethical conversations that consider available theoretical and philosophical models of claiming citizenship as a way of claiming values in uncertain times. Weeks (1995; 1998), Richardson (2000), Bell and Binnie (2000), and Phelan (2001) provides helpful guides to the struggle with tensions that faces us in lbgt/queer debates of citizenship. PMID- 17287196 TI - Ferment in LGBT studies and queer theory: personal ruminations on contested terrain. AB - The tensions between queer and gay rights theorists, not surprisingly, have grown as queer theory has developed and matured. In this self-reflexive essay, the "contested terrain" between these distinct perspectives is explored, particularly within the discipline of communication studies. The assumptions of queer theory are summarized briefly, and the author takes an autoethnographic approach to demonstrate the constant interplay between lived experience and the basic assumptions of queer theory. The author challenges both LGBT theorists and queer theorists to always consider the implications of their theories and practices. PMID- 17287197 TI - Inorganic mercury interacts with cysteine residues (C451 and C474) of hOCT2 to reduce its transport activity. AB - Human organic cation transporter 2 (hOCT2) is essential for the renal tubular secretion of many toxic organic cations. Previously, of the cysteines (C437, C451, C470, and C474) that occur within transmembrane helices that comprise the hydrophilic cleft (proposed site of substrate binding), only C474 was accessible to maleimide-PEO(2)-biotin (hydrophilic thiol-reactive reagent), and covalent modification of this residue caused lower transport rates (Pelis RM, Zhang X, Dangprapai Y, Wright SH, J Biol Chem 281: 35272-35280, 2006). Thus it was hypothesized that the environmental contaminant Hg(2+) (as HgCl(2)) would interact with C474 to reduce hOCT2-mediated transport. Uptake of [(3)H]tetraethylammonium (TEA) into Chinese hamster ovary cells stably expressing hOCT2 was reduced in a concentration-dependent manner by HgCl(2), with an IC(50) of 3.9 +/- 0.11 microM. Treatment with 10 microM HgCl(2) caused a sixfold reduction in the maximal rate of TEA transport but did not alter the affinity of hOCT2 for TEA. To determine which cysteines interact with Hg(2+), a mutant with all four cleft cysteines converted to alanines (quadruple mutant), and four variants of this mutant, each with an individual cysteine restored, were created. The quadruple mutant was less sensitive to HgCl(2) than wild-type, whereas the C451- and C474-containing mutants were more sensitive than the quadruple mutant. Consistent with the HgCl(2) effect on transport, MTSEA-biotin only interacted with C451 and C474. These data indicate that C451 and C474 of hOCT2 reside in the aqueous milieu of the cleft and that interaction of Hg(2+) with these residues causes reduced TEA transport activity. PMID- 17287198 TI - NHE8 mediates amiloride-sensitive Na+/H+ exchange across mosquito Malpighian tubules and catalyzes Na+ and K+ transport in reconstituted proteoliposomes. AB - Following a blood meal, the mosquito Aedes aegypti will have acquired an enormous sodium load that must be rapidly excreted to restore ion homeostasis. It is a process that demands robust sodium and fluid transport capabilities. Even though the identities of the components involved in this ion transport across the mosquito Malpighian tubule epithelia have not been completely determined, electrophysiological studies suggest the contribution of a Na(+)/H(+) exchanger extruding cations into the lumen driven secondarily by the proton gradient created by the V-type H(+)-ATPase in the tubules' apical membrane. We have identified the putative exchanger and designated it AeNHE8. Immunolocalization studies demonstrated that AeNHE8 is expressed in the apical membranes of Malpighian tubules, gastric caecae, and rectum. When heterologously expressed in salt-sensitive yeast cells lacking Na(+) extrusion and Na(+)/H(+) exchange proteins, AeNHE8 rescues the salt-sensitive phenotype and restores the cells' ability to grow in high NaCl media. Furthermore, heterologous expression of AeNHE8 in NHE-deficient fibroblast cells results in an amiloride-sensitive (22)Na(+) uptake. To determine the exchanger's kinetic properties, we reconstituted membranes from yeast cells expressing the protein into lipid proteoliposomes and assayed for cation-dependent H(+) exchange by fluorimetric methods. Our results indicate that AeNHE8 mediates saturable exchange of Na(+) and K(+) for H(+). We propose that AeNHE8 may be coupled to the inward H(+) gradient across the Malpighian tubules and plays a role in the extrusion of excess sodium and potassium while maintaining steady intracellular pH in the principal cells. PMID- 17287199 TI - Spinal glutamatergic NMDA-dependent pelvic nerve-to-external urethra sphincter reflex potentiation caused by a mechanical stimulation in anesthetized rats. AB - The current study investigates whether the spinal pelvic nerve-to-external urethra sphincter (EUS) reflex potentiation can be induced by a mechanical stimulation and whether the glutamatergic mechanism is involved in yielding such a reflex potentiation. The external urethra sphincter electromyogram (EUSE) activity, evoked by a single or by repetitive pelvic nerve stimulation, in 30 anesthetized rats was recorded with/without bladder saline distension. Without saline distension (0 cmH(2)O), a single pulse nerve stimulation evoked a single action potential in the reflex activity, whereas repetitive pelvic stimulation and saline distension (6 approximately 20 cmH(2)O) both elicited a long-lasting reflex potentiation (20.05 +/- 3.21 and 75.01 +/- 9.87 spikes/stimulation, respectively). The saline distension-induced pelvic nerve-to-EUS reflex potentiation was abolished by D-2-amino-5-phosphonovalerate [APV; a glutamatergic N -methyl-D-aspartic acid (NMDA) receptor antagonist; 100 microM, 10 microl, 1.72 +/- 0.31 spikes/stimulation] and attenuated by 2,3-dihydroxy-6-nitro-7-sulfamoyl benzo (F) quinoxaline [NBQX; a glutamatergic alpha-amino-3-hydroxy-5-methyl-4 isoxazoleproprionate (AMPA) receptor antagonist; 100 microM, 10 microl, 26.16 +/- 7.27 spikes/stimulation], but was not affected by bicuculline (a GABAergic antagonist; 100 microM, 10 microl, 53.62 +/- 15.54 spikes/stimulation). Intrathecal administration of glutamate (31.12 +/- 8.25 spikes/stimulation, 100 microM, 10 microl) and NMDA (26.25 +/- 4.12 spikes/stimulation, 100 microM, 10 microl) both induced a long-lasting pelvic nerve-to-EUS reflex potentiation without saline distension, which was similar to the findings observed from saline distension only. The duration of the contraction wave of the urethra was elongated by the saline distension-induced pelvic nerve-to-EUS reflex potentiation, whereas the peak pressure of the contraction wave was not affected. Our findings suggest that saline distension in the bladder elicits a pelvic nerve to-EUS reflex potentiation and the glutamatergic mechanism contributes to the presence of such a reflex potentiation. PMID- 17287201 TI - A murine transgenic model for transcriptional regulation of the Na/Pi-IIa major renal phosphate cotransporter. AB - Levels of the type IIa Na/P(i) (Na/Pi-IIa) cotransporter, which serves as the principal mediator of phosphate reabsorption in the kidney, can be modulated through posttranscriptional or posttranslational mechanisms by dietary, hormonal, and pharmacological influences. Previous studies have not demonstrated clear-cut evidence for modulation of Na/Pi-IIa cotransporter levels through transcriptional mechanisms. We have previously demonstrated that a 4.7-kb rat genomic fragment upstream of the rodent Npt2 gene encoding the Na/Pi-IIa cotransporter, is sufficient to mediate its transcriptional activity in vitro (Shachaf C, Skorecki KL, Tzukerman M. Am J Physiol Renal Physiol 278: F406-F416, 2000). Accordingly, we have established an in vivo experimental model in which this Npt2 genomic fragment fused upstream of a Lac Z reporter gene was expressed as a transgene in mice. The nine independent transgenic founder lines generated exhibited Lac Z reporter gene expression specifically in the renal cortex. This renal cortical specific expression driven by the Npt2 promoter was confirmed at the mRNA and protein levels using RT-PCR, histochemistry, and Lac Z enzymatic activity. Furthermore, the expression of the transgene correlated with expression of the endogenous Npt2 gene during embryonic and early postnatal development. Thus we have generated a transgenic mouse model which will enable in vivo investigation of the contribution of transcriptional mechanisms to the overall regulation of Na/Pi-IIa expression under physiological and pathophysiological conditions. PMID- 17287202 TI - History of personal dosimetry performance testing in the United States. AB - The basis for personal dosimetry performance testing in the United States is ANSI/HPS N13.11 (2001). Now in its third edition, this standard has been in place since 1983. Testing under this standard is administered by the National Voluntary Accreditation Program (NVLAP), and accreditation of dosimetry processors under this program is required by US Nuclear Regulatory Commission (NRC) regulations. The US Department of Energy (DOE) also maintains a testing program for its laboratories and contractors, administered by the Department of Energy Laboratory Accreditation Program (DOELAP). A focus in recent years has been the modification of ANSI/HPS N13.11 to allow acceptance by both testing programs in order to bring harmonisation to US personal dosemeter processing testing. Since there is no type testing program in the US for personal dosemeters, the testing philosophy of ANSI N13.11 has always combined elements of type testing and routine performance testing. This philosophy is explored in detail in this presentation, along with trends in the development of the document to its present state. In addition, a look will be taken at what the future holds for the next revision of the document, scheduled to begin in 2005. PMID- 17287200 TI - Alix (AIP1) is a vasopressin receptor (V2R)-interacting protein that increases lysosomal degradation of the V2R. AB - The vasopressin type 2 receptor (V2R) is a G protein-coupled receptor that plays a central role in renal water reabsorption. Termination of ligand (vasopressin) stimulation is an important physiological regulatory event, but few proteins that interact with the V2R during downregulation after vasopressin (VP) binding have been identified. Using yeast two-hybrid screening of a human kidney cDNA library, we show that a 100-kDa protein called ALG-2-interacting protein X (Alix) interacts with the last 29 amino acids of the V2R COOH terminus. This was confirmed by pull-down assays using a GST-V2R-COOH-tail fusion protein. Alix was immunolocalized in principal cells of the kidney, which also express the V2R. The function of the Alix-V2R interaction was studied by transfecting Alix into LLC PK(1) epithelial cells expressing V2R-green fluorescent protein (GFP). Under basal conditions, V2R-GFP localized mainly at the plasma membrane. On VP treatment, V2R-GFP was internalized into perinuclear vesicles in the nontransfected cells. In contrast, V2R-GFP fluorescence was virtually undetectable 2 h after exposure to VP in cells that coexpressed Alix. Western blotting using an anti-GFP antibody showed marked degradation of the V2R after 2 h in the presence of VP and Alix, a time point at which little or no degradation was detected in the absence of Alix. In contrast, little or no degradation of the parathyroid hormone receptor was detectable in the presence or absence of Alix and/or the PTH ligand. The VP-induced disappearance of V2R-GFP was abolished by chloroquine, a lysosomal degradation inhibitor, but not by MG132, a proteosome inhibitor. These data suggest that Alix increases the rate of lysosomal degradation of V2R and may play an important regulatory role in the VP response by modulating V2R downregulation. PMID- 17287204 TI - The microdosimetry of low-energy photons in radiotherapy. AB - Low energy photons are more and more in use in clinical practice, for treatment in radiotherapy as well as for imaging purposes. Their relative biological effectiveness is however still debated. In this paper, some microdosimetric parameters have been calculated for different sources: (125)I, (103)Pd, (131)Cs, an electronic brachytherapy source and various clinical mammography X-ray qualities. These parameters have been used to deduce the quality factors as defined in ICRU 40. PMID- 17287203 TI - Challenges and progress in predicting biological responses to incorporated radioactivity. AB - Prediction of risks and therapeutic outcome in nuclear medicine largely rely on calculation of the absorbed dose. Absorbed dose specification is complex due to the wide variety of radiations emitted, non-uniform activity distribution, biokinetics, etc. Conventional organ absorbed dose estimates assumed that radioactivity is distributed uniformly throughout the organ. However, there have been dramatic improvements in dosimetry models that reflect the substructure of organs as well as tissue elements within them. These models rely on improved nuclear medicine imaging capabilities that facilitate determination of activity within voxels that represent tissue elements of approximately 0.2-1 cm(3). However, even these improved approaches assume that all cells within the tissue element receive the same dose. The tissue element may be comprised of a variety of cells having different radiosensitivities and different incorporated radioactivity. Furthermore, the extent to which non-uniform distributions of radioactivity within a small tissue element impact the absorbed dose distribution is strongly dependent on the number, type, and energy of the radiations emitted by the radionuclide. It is also necessary to know whether the dose to a given cell arises from radioactive decays within itself (self-dose) or decays in surrounding cells (cross-dose). Cellular response to self-dose can be considerably different than its response to cross-dose from the same radiopharmaceutical. Bystander effects can also play a role in the response. Evidence shows that even under conditions of 'uniform' distribution of radioactivity, a combination of organ dosimetry, voxel dosimetry and dosimetry at the cellular and multicellular levels can be required to predict response. PMID- 17287206 TI - Improved measurements of neutron dose equivalent rates using a dual instrument technique. AB - A dual instrument technique, employing a neutron area survey meter and a tissue equivalent proportional counter, has been developed to improve the measurement of neutron dose equivalent rates in workplace fields. A simple algorithm estimates the ambient dose equivalent response of the area survey meter from the ratio of the dose equivalent rates measured by the two instruments. This estimate can then be used to adjust the reading from the area survey meter, providing a better measure of the neutron ambient dose equivalent rate in the workplace. The technique was tested on 225 spectra from the neutron spectrum catalogue SPKTBIB. PMID- 17287205 TI - Integration of external and internal dosimetry in Switzerland. AB - Individual monitoring regulations in Switzerland are based on the ICRP60 recommendations. The annual limit of 20 mSv for the effective dose applies to the sum of external and internal radiation. External radiation is monitored monthly or quarterly with TLD, DIS or CR-39 dosemeters by 10 approved external dosimetry services and reported as Hp(10) and Hp(0.07). Internal monitoring is done in two steps. At the workplace, simple screening measurements are done frequently in order to recognise a possible incorporation. If a nuclide dependent activity threshold is exceeded then one of the seven approved dosimetry services for internal radiation does an incorporation measurement to assess the committed effective dose E50. The dosimetry services report all the measured or assessed dose values to the employer and to the National Dose Registry. The employer records the annually accumulated dose values into the individual dose certificate of the occupationally exposed person, both the external dose Hp(10) and the internal dose E50 as well as the total effective dose E=Hp(10)+E50. Based on the national dose registry an annual report on the dosimetry in Switzerland is published which contains the statistics for the total effective dose, as well as separate statistics for external and internal exposure. PMID- 17287207 TI - Comparing alcohol consumption in central and eastern Europe to other European countries. AB - AIMS: To give an overview of the volume of alcohol consumption, beverage preference, and patterns of drinking among adults (people 15 years and older) in central and eastern Europe (Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia) and to compare it to southern and western Europe, Russia and Ukraine. METHODS: Secondary data analysis. Consumption and preferred beverage type data for the year 2002 were taken from the WHO Global Status Report on Alcohol and the WHO Global Alcohol Database. RESULTS: Average consumption in central and eastern Europe is high with a relatively large proportion of unrecorded consumption ranging from one litre in Czech Republic and Estonia to 10.5 l in Ukraine. The proportion of heavy alcohol consumption (more than 40 g of pure alcohol per day) among men was the lowest in Bulgaria (25.8%) and the highest in Czech Republic (59.4%). Among women, the lowest proportion of heavy alcohol consumption was registered in Estonia (4.0%) and the highest in Hungary (16.0%). Patterns of drinking are detrimental with a high proportion of binge drinking, especially in the group of countries traditionally drinking vodka. In most countries, beer is now the most prevalent alcoholic beverage. CONCLUSIONS: Other studies suggest that the population drinking levels found in central and eastern Europe are linked with higher levels of detrimental health outcomes. Known effective and cost-effective programs to reduce levels of risky drinking should, therefore, be implemented, which may, in turn, lead to a reduction of alcohol-attributable burden of disease. PMID- 17287210 TI - Mannose foraging by Bacteroides thetaiotaomicron: structure and specificity of the beta-mannosidase, BtMan2A. AB - The human colonic bacterium Bacteroides thetaiotaomicron, which plays an important role in maintaining human health, produces an extensive array of exo acting glycoside hydrolases (GH), including 32 family GH2 glycoside hydrolases. Although it is likely that these enzymes enable the organism to utilize dietary and host glycans as major nutrient sources, the biochemical properties of these GH2 glycoside hydrolases are currently unclear. Here we report the biochemical properties and crystal structure of the GH2 B. thetaiotaomicron enzyme BtMan2A. Kinetic analysis demonstrates that BtMan2A is a beta-mannosidase in which substrate binding energy is provided principally by the glycone binding site, whereas aglycone recognition is highly plastic. The three-dimensional structure, determined to a resolution of 1.7 A, reveals a five-domain structure that is globally similar to the Escherichia coli LacZ beta-galactosidase. The catalytic center is housed mainly within a (beta/alpha)8 barrel although the N-terminal domain also contributes to the active site topology. The nature of the substrate binding residues is quite distinct from other GH2 enzymes of known structure, instead they are similar to other clan GH-A enzymes specific for manno-configured substrates. Mutagenesis studies, informed by the crystal structure, identified a WDW motif in the N-terminal domain that makes a significant contribution to catalytic activity. The observation that this motif is invariant in GH2 mannosidases points to a generic role for these residues in this enzyme class. The identification of GH-A clan and GH2 specific residues in the active site of BtMan2A explains why this enzyme is able to harness substrate binding at the proximal glycone binding site more efficiently than mannan-hydrolyzing glycoside hydrolases in related enzyme families. The catalytic properties of BtMan2A are consistent with the flexible nutrient acquisition displayed by the colonic bacterium. PMID- 17287209 TI - A Novel TRAF6 binding site in MALT1 defines distinct mechanisms of NF-kappaB activation by API2middle dotMALT1 fusions. AB - The recurrent translocation t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue (MALT) lymphoma results in the expression of an API2.MALT1 fusion protein that constitutively activates NF-kappaB. The first baculovirus IAP repeat (BIR) domain of API2 and the C terminus of MALT1, which contains its caspase-like domain, are present in all reported fusion variants and interact with TRAF2 and TRAF6, respectively, suggesting their contribution to NF-kappaB signaling by API2.MALT1. Also, the involvement of BCL10 has been suggested via binding to BIR1 of API2 and via its interaction with the immunoglobulin domains of MALT1, present in half of the fusion variants. However, conflicting reports exist concerning their roles in API2.MALT1-induced NF-kappaB signaling. In this report, streptavidin pulldowns of biotinylated API2.MALT1 fusion variants showed that none of the fusion variants interacted with endogenous BCL10; its role in NF kappaB signaling by API2.MALT1 was further questioned by RNA interference experiments. In contrast, TRAF6 was essential for NF-kappaB activation by all fusion variants, and we identified a novel TRAF6 binding site in the second immunoglobulin domain of MALT1, which enhanced NF-kappaB activation when present in the fusion protein. Furthermore, inclusion of both immunoglobulin domains in API2.MALT1 further enhanced NF-kappaB signaling via intramolecular TRAF6 activation. Finally, binding of TRAF2 to BIR1 contributed to NF-kappaB activation by API2.MALT1, although additional mechanisms involving BIR1-mediated raft association are also important. Taken together, these data reveal distinct mechanisms of NF-kappaB activation by the different API2.MALT1 fusion variants with an essential role for TRAF6. PMID- 17287211 TI - Deactivation and proton transfer in light-induced metarhodopsin II/metarhodopsin III conversion: a time-resolved fourier transform infrared spectroscopic study. AB - Vertebrate rhodopsin shares with other retinal proteins the 11-cis-retinal chromophore and the light-induced 11-cis/trans isomerization triggering its activation pathway. However, only in rhodopsin the retinylidene Schiff base bond to the apoprotein is eventually hydrolyzed, making a complex regeneration pathway necessary. Metabolic regeneration cannot be short-cut, and light absorption in the active metarhodopsin (Meta) II intermediate causes anti/syn isomerization around the retinylidene linkage rather than reversed trans/cis isomerization. A new deactivating pathway is thereby triggered, which ends in the Meta III "retinal storage" product. Using time-resolved Fourier transform infrared spectroscopy, we show that the identified steps of receptor activation, including Schiff base deprotonation, protein structural changes, and proton uptake by the apoprotein, are all reversed. However, Schiff base reprotonation is much faster than the activating deprotonation, whereas the protein structural changes are slower. The final proton release occurs with pK approximately 4.5, similar to the pK of a free Glu residue and to the pK at which the isolated opsin apoprotein becomes active. A forced deprotonation, equivalent to the forced protonation in the activating pathway, which occurs against the unfavorable pH of the medium, is not observed. This explains properties of the final Meta III product, which displays much higher residual activity and is less stable than rhodopsin arising from regeneration with 11-cis-retinal. We propose that the anti/syn conversion can only induce a fast reorientation and distance change of the Schiff base but fails to build up the full set of dark ground state constraints, presumably involving the Glu(134)/Arg(135) cluster. PMID- 17287208 TI - Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. AB - Increased transcriptional activity of beta-catenin resulting from Wnt/Wingless dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation is poorly understood. We have demonstrated that AKT, which is activated downstream from epidermal growth factor receptor signaling, phosphorylates beta-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of beta-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3zeta via a binding motif containing Ser552. Phosphorylation of beta-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT dependent regulation of beta-catenin plays a critical role in tumor invasion and development. PMID- 17287212 TI - The role of AMPK and mTOR in nutrient sensing in pancreatic beta-cells. AB - The AMP-activated protein kinase (AMPK) is a central regulator of the energy status of the cell, based on its unique ability to respond directly to fluctuations in the ratio of AMP:ATP. Because glucose and amino acids stimulate insulin release from pancreatic beta-cells by the regulation of metabolic intermediates, AMPK represents an attractive candidate for control of beta-cell function. Here, we show that inhibition of AMPK in beta-cells by high glucose inversely correlates with activation of the mammalian Target of Rapamycin (mTOR) pathway, another cellular sensor for nutritional conditions. Forced activation of AMPK by AICAR, phenformin, or oligomycin significantly blocked phosphorylation of p70S6K, a downstream target of mTOR, in response to the combination of glucose and amino acids. Amino acids also suppressed the activity of AMPK, and this at a minimum required the presence of leucine and glutamine. It is unlikely that the ability of AMPK to sense both glucose and amino acids plays a role in regulation of insulin secretion, as inhibition of AMPK by amino acids did not influence insulin secretion. Moreover, activation of AMPK by AICAR or phenformin did not antagonize glucose-stimulated insulin secretion, and insulin secretion was also unaffected in response to suppression of AMPK activity by expression of a dominant negative AMPK construct (K45R). Taken together, these results suggest that the inhibition of AMPK activity by glucose and amino acids might be an important component of the mechanism for nutrient-stimulated mTOR activity but not insulin secretion in the beta-cell. PMID- 17287213 TI - Crystal structure of the RNA polymerase domain of the West Nile virus non structural protein 5. AB - Viruses of the family Flaviviridae are important human and animal pathogens. Among them, the Flaviviruses dengue (DENV) and West Nile (WNV) cause regular outbreaks with fatal outcomes. The RNA-dependent RNA polymerase (RdRp) activity of the non-structural protein 5 (NS5) is a key activity for viral RNA replication. In this study, crystal structures of enzymatically active and inactive WNV RdRp domains were determined at 3.0- and 2.35-A resolution, respectively. The determined structures were shown to be mostly similar to the RdRps of the Flaviviridae members hepatitis C and bovine viral diarrhea virus, although with unique elements characteristic for the WNV RdRp. Using a reverse genetic system, residues involved in putative interactions between the RNA-cap methyltransferase (MTase) and the RdRp domain of Flavivirus NS5 were identified. This allowed us to propose a model for the structure of the full-length WNV NS5 by in silico docking of the WNV MTase domain (modeled from our previously determined structure of the DENV MTase domain) onto the RdRp domain. The Flavivirus RdRp domain structure determined here should facilitate both the design of anti-Flavivirus drugs and structure-function studies of the Flavivirus replication complex in which the multifunctional NS5 protein plays a central role. PMID- 17287214 TI - Crystal structure of the heme-IsdC complex, the central conduit of the Isd iron/heme uptake system in Staphylococcus aureus. AB - Pathogens such as Staphylococcus aureus require iron to survive and have evolved specialized proteins to steal heme from their host. IsdC is the central conduit of the Isd (iron-regulated surface determinant) multicomponent heme uptake machinery; staphylococcal cell-surface proteins such as IsdA, IsdB, and IsdH are thought to funnel their molecular cargo to IsdC, which then mediates the transfer of the iron-containing nutrient to the membrane translocation system IsdDEF. The structure of the heme-IsdC complex reveals a novel heme site within an immunoglobulin-like domain and sheds light on its binding mechanism. The folding topology is reminiscent of the architecture of cytochrome f, cellobiose dehydrogenase, and ethylbenzene dehydrogenase; in these three proteins, the heme is bound in an equivalent position, but interestingly, IsdC features a distinct binding pocket with the ligand located next to the hydrophobic core of the beta sandwich. The iron is coordinated with a tyrosine surrounded by several non-polar side chains that cluster into a tightly packed proximal side. On the other hand, the distal side is relatively exposed with a short helical peptide segment that acts as a lip clasping onto almost half of the porphyrin plane. This structural feature is argued to play a role in the mechanism of binding and release by switching to an open conformation and thus loosening the interactions holding the heme. The structure of the heme-IsdC complex provides a template for the understanding of other proteins, such as IsdA, IsdB, and IsdH, that contain the same heme-binding module as IsdC, known as the NEAT (near transporter) domain. PMID- 17287215 TI - Crystal structure of the serine protease domain of prophenoloxidase activating factor-I. AB - A family of serine proteases (SPs) mediates the proteolytic cascades of embryonic development and immune response in invertebrates. These proteases, called easter type SPs, consist of clip and chymotrypsin-like SP domains. The SP domain of easter-type proteases differs from those of typical SPs in its primary structure. Herein, we report the first crystal structure of the SP domain of easter-type proteases, presented as that of prophenoloxidase activating factor (PPAF)-I in zymogen form. This structure reveals several important structural features including a bound calcium ion, an additional loop with a unique disulfide linkage, a canyon-like deep active site, and an exposed activation loop. We subsequently show the role of the bound calcium and the proteolytic susceptibility of the activation loop, which occurs in a clip domain-independent manner. Based on biochemical study in the presence of heparin, we suggest that PPAF-III, highly homologous to PPAF-I, contains a surface patch that is responsible for enhancing the catalytic activity through interaction with a nonsubstrate region of a target protein. These results provide insights into an activation mechanism of easter-type proteases in proteolytic cascades, in comparison with the well studied blood coagulation enzymes in mammals. PMID- 17287216 TI - Lysophosphatidic acid induces interleukin-13 (IL-13) receptor alpha2 expression and inhibits IL-13 signaling in primary human bronchial epithelial cells. AB - Interleukin-13 (IL-13), a Th2 cytokine, plays a pivotal role in pathogenesis of bronchial asthma via IL-13 receptor alpha1 (IL-13Ralpha1) and IL-4 receptor alpha (IL-4Ralpha). Recent studies show that a decoy receptor for IL-13, namely IL 13Ralpha2, mitigates IL-13 signaling and function. This study provides evidence for regulation of IL-13Ralpha2 production and release and IL-13-dependent signaling by lysophosphatidic acid (LPA) in primary cultures of human bronchial epithelial cells (HBEpCs). LPA treatment of HBEpCs in at imedependent fashion increased IL-13Ralpha2 gene expression without altering the mRNA levels of IL 13Ralpha1 and IL-4Ralpha. Pretreatment with pertussis toxin (100 ng/ml, 4 h) or transfection of c-Jun small interference RNA or an inhibitor of JNK attenuated LPA-induced IL-13Ralpha2 gene expression and secretion of soluble IL-13Ralpha2. Overexpression of catalytically inactive mutants of phospholipase D (PLD) 1 or 2 attenuated LPA-induced IL-13Ralpha2 gene expression and protein secretion as well as phosphorylation of JNK. Pretreatment of HBEpCs with 1 microM LPA for 6 h attenuated IL-13-but not IL-4-induced phosphorylation of STAT6. Transfection of HBEpCs with IL-13Ralpha2 small interference RNA blocked the effect of LPA on IL 13-induced phosphorylation of STAT6. Furthermore, pretreatment with LPA (1 microM, 6 h) attenuated IL-13-induced eotaxin-1 and SOCS-1 gene expression. These results demonstrate that LPA induces IL-13Ralpha2 expression and release via PLD and JNK/AP-1 signal transduction and that pretreatment with LPA down-regulates IL 13 signaling in HBEpCs. Our data suggest a novel mechanism of regulation of IL 13Ralpha2 and IL-13 signaling that may be of physiological relevance to airway inflammation and remodeling. PMID- 17287217 TI - Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. AB - CD26 is a widely distributed 110-kDa cell surface glycoprotein with an important role in T-cell costimulation. We demonstrated previously that CD26 binds to caveolin-1 in antigen-presenting cells, and following exogenous CD26 stimulation, Tollip and IRAK-1 disengage from caveolin-1 in antigen-presenting cells. IRAK-1 is then subsequently phosphorylated to up-regulate CD86 expression, resulting in subsequent T-cell proliferation. However, it is unclear whether caveolin-1 is a costimulatory ligand for CD26 in T-cells. Using soluble caveolin-1-Fc fusion protein, we now show that caveolin-1 is the costimulatory ligand for CD26, and that ligation of CD26 by caveolin-1 induces T-cell proliferation and NF-kappaB activation in a T-cell receptor/CD3-dependent manner. We also demonstrated that the cytoplasmic tail of CD26 interacts with CARMA1 in T-cells, resulting in signaling events that lead to NF-kappaB activation. Ligation of CD26 by caveolin 1 recruits a complex consisting of CD26, CARMA1, Bcl10, and IkappaB kinase to lipid rafts. Taken together, our findings provide novel insights into the regulation of T-cell costimulation via the CD26 molecule. PMID- 17287219 TI - Children in handcuffs and detained behind bars. Where in the world? PMID- 17287218 TI - Nephroprotective effect of the HMG-CoA-reductase inhibitor cerivastatin in a mouse model of progressive renal fibrosis in Alport syndrome. AB - BACKGROUND: Alport syndrome is caused by mutations in genes encoding for the alpha3, alpha4 or alpha5 chain of type IV collagen leading to excessive production of fibrotic tissue and end-stage renal failure. HMG-CoA-reductase inhibitors exhibit pleiotropic effects by which they modulate the production of connective tissue. The aim of this study was to examine the anti-fibrotic effect of the HMG-CoA-reductase-inhibitor, cerivastatin, in COL4A3 knockout mice, an animal model of Alport syndrome with progressive renal fibrosis. METHODS: Forty homozygous COL4A3 knockout mice received cerivastatin, starting 28 or 49 days after birth. Mice were sacrificed at day 52 or 66 after birth. Immunohistochemistry against laminin and fibronectin was performed. Inflammatory cell infiltration was determined by F4/80- and CD3-staining. Myofibroblasts were identified by an alpha-smooth muscle actin staining. Expression of the profibrotic cytokines, TGF-beta1 and CTGF, were determined by immunoblot. RESULTS: The lifespan of treated COL4A3 knockout mice was increased by 28% compared with untreated animals (71+/-6 vs 91+/-9 days, P<0.01). Early cerivastatin treatment reduced cholesterol levels (113+/-13 vs 141+/-19 mmol/l in untreated animals, P<0.05) and serum urea (164 vs 235 mmol/l, day 66, P<0.05). Treatment also decreased proteinuria (5.5 vs 12 g/l at day 66, P<0.05). Deposition of laminin and fibronectin, expression of TGF-beta and CTGF was reduced. Infiltration of T-cells and macrophages as well as myofibroblasts appeared to be reduced in kidneys from cerivastatin-treated mice. CONCLUSION: Cerivastatin prolongs the lifespan of COL4A3 knockout mice, reduces proteinuria and delays uraemia. These effects are associated with decreased renal fibrosis and a reduction of inflammatory cell infiltration. PMID- 17287220 TI - Revisiting Goffman's Stigma: the social experience of families with children requiring mechanical ventilation at home. AB - This article argues for a sociologically grounded theoretical orientation for the study of selected health phenomena. Erving Goffman's theory of stigma provides a framework for better understanding the social dimension of the lives of disabled children and their families. First, the principal tenets of this theory are reviewed. Then, the findings from a study of the moral experience of families with children requiring mechanical ventilation at home are re-examined in light of Goffman's Stigma. This analysis highlights how a sociological framework can help advance our understanding of medical problems as social problems and shed light on socialization processes that can help resolve the discrediting, isolation and distress lived by disabled children and their families. PMID- 17287221 TI - Development of children's assent documents using a child-centred approach. AB - The call for researchers to obtain children's informed assent, prior to their participation in medical procedures and research, has increased over recent years and parallels moves to implement child-centred approaches to health care. This article describes the processes used to include children in developing a research information sheet and assent form for use in future research into children's understandings of their surgery and hospital experiences. The process involved primary school children aged between six and 12 years. Children worked in small groups to consider information to include in these documents. Their words were collated to construct the research information sheet and assent form. Working with children resulted in documents that were more understandable for their intended audience. The article includes discussion of 'language', 'understandability' and 'readability'; concepts that researchers seeking to work with children need to come to terms with if they are to obtain 'informed assent'. PMID- 17287222 TI - 'If I was in my daughter's body I'd be feeling devastated': women's experiences of mothering an overweight or obese child. AB - Overweight and obesity in children is a major and ongoing public health concern and the negative physical, social, and psychological sequelae of childhood obesity are well documented. Parents, particularly mothers, are implicated in discourses around childhood obesity; however, little is known about women's experiences of mothering an overweight or obese child. This article reports findings from a narrative-based study that sought to develop understandings into women's experiences of mothering an overweight or obese child. The findings provide insights into the experiences of mothering an overweight or obese child, and reveals how the climate of blame associated with mothering an overweight or obese child complicated the mothering experience for the women in this study. These insights can assist health, welfare and child care workers to understand the importance of establishing supportive and no-blame relationships with mothers of obese and overweight children, in order to develop supportive therapeutic alliances better. PMID- 17287223 TI - Caring for a child with Juvenile Huntington's Disease: helpful and unhelpful support. AB - There has been little research into the psychosocial impact of Juvenile Huntington's Disease on the child and family. This study investigates the social and health care needs of those affected by Juvenile Huntington's Disease. Ten semi-structured interviews with carers were analysed using the qualitative methodology interpretative phenomenological analysis. This article reports three themes on the social support that families received. The first theme describes how parents perceived the support that they received from family and friends. The second and third themes describe how parents perceived helpful and unhelpful experiences of professional support. This corresponds to the view that social support is a 'double-edged sword', which can both ameliorate the effects of, and be a source of, stress. This information should be useful to those supporting the family of a child with a chronic or terminal illness. PMID- 17287224 TI - Care of hospitalized children in Mozambique: nurses' beliefs and practice regarding family involvement. AB - This study aims to describe nurses' beliefs and practice regarding family involvement in the care of hospitalized children in Mozambique. Ethnographic fieldwork was used. The data production consisted of field descriptions from observations and interviews with 36 nurses. Through qualitative content analysis the findings show that nurses' practice of family involvement reflects a society that is poor, hierarchical, family-oriented but at the same time still adaptive. Four themes are identified: family members' presence in order to assist the nurses in care; nurses' support and education of family members to be involved in care; nurses' shielding of family members from family involvement; difficulties and conditional dilemmas in the nurses' involvement of families. It is concluded that emphasizing culturally congruent nursing care is necessary if families' way of life is to be accommodated. However, to empower family involvement in everyday practice, the Mozambican nurses themselves need to be empowered. PMID- 17287225 TI - Consent in severely disabled children: informed or an infringement of their human rights? AB - In this article the issue of consent in children is examined with particular reference to disabled children and young people. It is demonstrated that gaining informed consent from disabled children is still a long way off and that the issues are not clear. The law delivers contradictory rulings, parents and families are becoming more vocal in challenging doctors, and the courts are becoming increasingly involved in decision-making on treatment options. The Human Rights Act 1998 is becoming more prominent in informing these decisions. The article concludes that these developments may not be in the best interests of disabled children and that strategies are needed to help them communicate their views. PMID- 17287227 TI - Consumers with an intellectual disability and carers: perceptions of interactions with banks. AB - As more people with an intellectual disability reside independently in the community, there is both the need and the opportunity for them to use financial services, including banks and credit unions, and products such as cash machine cards, credit cards and loans. There is a dearth of information about interactions between consumers with intellectual disabilities and their carers, and financial service providers. This study investigated the perceptions of 94 consumers with an intellectual disability and 53 carers regarding interactions with financial service providers. Consumers and carers mentioned a number of problems with banks, and reported a low rate of successful resolution of these difficulties. Carers mentioned more problems than consumers, and more frequently reported intangible problems such as discrimination. The 'digital divide' was evident, with few consumers having access to Internet or telephone banking. People with intellectual disabilities need education programmes about electronic banking, their rights as consumers and their access to problem resolution strategies. PMID- 17287228 TI - Assessing learning styles of adults with intellectual difficulties. AB - The development of an electronic inventory to assess learning styles of adults with intellectual difficulties was seen as an inclusion strategy to aid learning and achievement. Some argue for the 'centrality of e-learning to educational diversity', for example. The use of VAK inventories (whether electronic or paper based), however, has been derogated as leading to theory-practice pedagogy that is misinterpreted and ill-informed. The focus here is dual in that the vigour and 'user friendliness' of the tool developed is analysed in the midst of a critical appraisal of its use. Assessments conducted using the inventory developed showed 34 percent of the participants have visual preferences, 34 percent have auditory, 23 percent have kinaesthetic, and 9 percent have multimodal learning preferences. Thus, this participant group requires a varied and diverse learning programme. The inventory was found to be user friendly but in need of further development, and would best be used as part of a self-reflective learning package. PMID- 17287229 TI - Care staff attributions toward self-injurious behaviour exhibited by adults with intellectual disabilities. AB - Challenging behaviours may elicit negative emotional reactions and increase stress within care staff. The Leeds Attributional Coding System (LACS) was used to elicit spontaneous causal attributions of staff toward hypothetical clients with challenging behaviours. It was hypothesized that there would be relationships (1) between staff exposure to challenging behaviours and burnout, and (2) between staff cognitions and burnout. Using a cross-sectional correlational design, 41 care staff took part in a 10 minute interview about two vignettes depicting self-injurious behaviour. Staff also completed measures of demographic information and burnout. Participants made attributions toward self injurious behaviour that were typically internal to the client, uncontrollable, unstable and specific. There was a significant association between number of clients cared for and emotional exhaustion and personal accomplishment. Staff who made fewer stable attributions had higher levels of burnout. There were no other relationships found between staff cognition and burnout. The LACS can be successfully employed in this context, and may have some benefits over other methods. Future research is required to explore the relationship between cognition and burnout. PMID- 17287230 TI - Working on person-centred planning: from amber to green light? AB - This article reviews the practice and policy based literature on person-centred planning in learning disability services in England. Its aim is to identify the implications for the workforce in practice.The analysis found that implementation is often described as partial or slow and characterizes reasons for this at a number of levels, including the slow pace of change in service culture and power relations, immutable funding structures, services' inflexible infrastructures, high levels of staff turnover and lack of training, inexperience among service management, inadequate staff supervision, and ambiguity among some stakeholders. Little substantial critique exists of the model itself. Analysis of the literature further reveals that the implementation of person-centred planning in practice is assisted by policy encouragement, service development and investment, favourable case reports and personal accounts, practitioner enthusiasm and positive evaluations. This article explores these to consider what facilitates the adoption of new elements of practice. PMID- 17287231 TI - A tale of two White Papers: policy documents as indicators of trends in UK services. AB - Cross-cultural differences in governance and policies for learning disability services are of interest. This article focuses on two UK government policy documents issued in 1971 and 2001. Their context, creation, principles, proposals and proposed implementation are examined, and lessons are drawn for an international audience as to the changing nature of services in the UK. The analysis reveals a move from a detailed and prescriptive policy in 1971, largely defined by professionals and bureaucrats, and aimed primarily at families with a disabled member, to statements of broad principles in 2001, devised in consultation with and aimed at a range of groups, including disabled people themselves. The article acknowledges progress in individual rights and choices for people with learning disabilities, but raises doubts about how significant this is in achieving a qualitative improvement in their lives. Some of these doubts relate to the governance process itself. PMID- 17287232 TI - Restraint and self-injury in people with intellectual disabilities: a review. AB - Most of the recent debate concerning the ethics of physical interventions has focused on the management of aggressive and destructive behaviours, neglecting the management of self-injurious behaviour. This is an important omission, given the extremely serious consequences that can arise from this form of challenging behaviour. The present article reviews types of restraint used to manage self injury, prevalence of use, and main and side effects of restraint use. It describes some good practice standards and highlights the need for further research and debate in this complex area. PMID- 17287234 TI - Imaging of vertebral artery stenosis: a systematic review. AB - BACKGROUND AND PURPOSE: Posterior circulation stroke accounts for 20% of ischaemic strokes. Recent data suggest that the early stroke recurrence risk is high and comparable with carotid artery disease. Vertebral artery stenosis accounts for approximately 20% of posterior circulation stroke, and with endovascular treatment available accurate diagnostic imaging is important. We performed a systematic literature review to validate the accuracy of the non invasive imaging techniques Duplex ultrasound (DUS), magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) in detecting severe vertebral artery stenosis, with intra-arterial angiography (IAA) as the reference standard. METHODS: We identified studies that used non-invasive imaging and IAA as the reference standard to determine vertebral artery stenosis and provided adequate data to calculate sensitivity and specificity. We analysed the quality of these studies, looked for evidence of heterogeneity and performed subgroup analysis for different degrees of stenosis. RESULTS: 11 studies categorised stenosis into 50-99%. The sensitivity of CTA (single study) and pooled sensitivities of contrast enhanced MRA (CE-MRA) and colour duplex were 100% (95% CI 15.8 to 100), 93.9% (79.8 to 99.3) and 70.2% (54.2 to 83.3), respectively. The specificities for CTA, CE-MRA and colour duplex were 95.2% (83.8 to 99.4), 94.8% (91.1 to 97.3) and 97.7% (95.2 to 99.1). However, specificities for CE-MRA and colour duplex demonstrated significant heterogeneity (p = 0.003 and p = 0.002, respectively). CONCLUSIONS: CE-MRA and possibly CTA may be more sensitive in diagnosing vertebral artery stenosis than DUS. However, data are limited and further high quality studies comparing DUS, MRA and CTA with IAA are required. PMID- 17287235 TI - Magnetisation transfer ratio in the normal appearing white matter predicts progression of disability over 1 year in early primary progressive multiple sclerosis. AB - BACKGROUND: Progression rates in primary progressive multiple sclerosis (PPMS) vary widely and brain magnetisation transfer imaging (MTI) has potential as an early prognostic indicator. We investigated the predictive value of MTI and the longitudinal changes developing over 1 year in early PPMS. AIMS: To determine (1) whether baseline brain MTI parameters in early PPMS predict clinical changes over 1 year, independent of brain volume and (2) whether a change in magnetisation transfer (MT) parameters occurs over 1 year, independent of atrophy. METHODS: 30 patients with PPMS within 5 years of symptom onset and 15 controls underwent MT and volumetric imaging studies, at baseline and at 1 year. Patients underwent clinical assessment using the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC), including the timed walk subtest (TWT). Normalised MT histograms were generated for whole brain, normal appearing brain tissue (NABT) and normal appearing white and grey matter (NAWM and NAGM) segments. Multiple regression analyses were performed to investigate whether baseline MTR parameters predicted clinical change over 1 year, adjusting for baseline brain volume. MTR changes over 1 year were assessed using paired t tests. RESULTS: In patients, lower baseline NAWM MTR predicted greater deterioration in EDSS and MSFC, particularly in walking ability measured by the TWT, independent of NAWM baseline volume (p = 0.001). NAGM MTR mean (p<0.001), and to a lesser extent NAWM mean (p = 0.011) and lesion MTR (p = 0.03), decreased over 1 year. CONCLUSIONS: NAWM MTR may provide information on short term clinical prognosis in early PPMS. MTI is sensitive to brain tissue changes over 1 year in early PPMS, which were primarily seen in the NAGM. PMID- 17287236 TI - Profile of cognitive impairment in dementia associated with Parkinson's disease compared with Alzheimer's disease. AB - OBJECTIVE: To compare the profile of cognitive impairment in Alzheimer's disease (AD) with dementia associated with Parkinson's disease (PDD). METHODS: Neuropsychological assessment was performed in 488 patients with PDD and 488 patients with AD using the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Logistic regression analysis was used to investigate whether the diagnosis could be accurately predicted from the cognitive profile. Additionally, the cognitive profiles were compared with a normative group using standardised effect sizes (Cohen's d). RESULTS: Diagnosis was predicted from the cognitive profile, with an overall accuracy of 74.7%. Poor performance of the AD patients on the orientation test in ADAS-cog best discriminated between the groups, followed by poor performance of the PDD patients on the attentional task in MMSE. Both groups showed memory impairment, AD patients performing worse than PDD patients. CONCLUSION: The cognitive profile in PDD differs significantly from that in AD. Performance on tests of orientation and attention are best in differentiating the groups. PMID- 17287237 TI - Apolipoprotein E and traumatic brain injury in a military population: evidence of a neuropsychological compensatory mechanism? AB - OBJECTIVE: Although research has implicated the apolipoprotein E (APOE) epsilon-4 genotype as having a negative effect on neuropsychological outcomes following traumatic brain injury (TBI), the potentially negative role of the epsilon4 allele on TBI outcomes has recently been challenged. In light of this debate, the present study served to examine the role of APOE genotype on neuropsychological outcomes approximately 1 month following mild to moderate TBI in a military population. Because of the well documented role of the APOE-epsilon4 allele in increasing the risk of Alzheimer's disease, we predicted that persons with the APOE-epsilon4 genotype would display relatively greater deficits in cognition than their non-epsilon4 counterparts. METHODS: 78 participants were consecutively recruited following a mild to moderate TBI and were divided into two groups based on the presence or absence of an APOE epsilon4 allele. Groups were comparable on demographic characteristics and psychosocial outcomes. Participants were administered a comprehensive neuropsychological battery. RESULTS: Analyses revealed comparable performances on most neuropsychological measures and better performances by epsilon4 carriers on select measures of attention, executive functioning and episodic memory encoding. Furthermore, differences remained after accounting for the effects of TBI severity. CONCLUSIONS: Evidence from these analyses supports current literature refuting the notion of relatively poorer neuropsychological functioning associated with the APOE-epsilon4 genotype among young adult participants shortly following mild or moderate brain injury. Neuropsychological performance differences by APOE genotype following TBI are discussed in terms of the importance of considering severity of injury, timing of postinjury assessment and possible neurocognitive compensatory mechanisms. PMID- 17287238 TI - Hippocampal activation in patients with mild cognitive impairment is necessary for successful memory encoding. AB - BACKGROUND: Episodic memory enables us to consciously recollect personally experienced past events. Memory performance is reduced in patients with mild cognitive impairment (MCI), an at-risk condition for Alzheimer's disease (AD). PATIENTS AND METHODS: We used functional MRI (fMRI) to compare brain activity during memory encoding in 29 healthy elderly subjects (mean age 67.7 (SD 5.4) years) and 21 patients with MCI (mean age 69.7 (SD 7.0) years). Subjects remembered a list of words while fMRI data were acquired. Later, they had to recognise these words among a list of distractor words. The use of an event related paradigm made it possible to selectively analyse successfully encoded items in each individual. We compared activation for successfully encoded words between healthy elderly subjects and patients with MCI. RESULTS: The main intergroup difference was found in the left hippocampus and surrounding medial temporal lobe (MTL) regions for the patients with MCI compared with healthy subjects during successful encoding. CONCLUSION: These results suggest that in patients with MCI, an increase in MTL activation is necessary for successful memory encoding. Hippocampal activation may help to link newly learned information to items already stored in memory. Increased activation in MTL regions in MCI may reflect a compensatory response to the beginning of AD pathology. PMID- 17287239 TI - Focal cortical dysplasia: long term seizure outcome after surgical treatment. AB - BACKGROUND: Studies of long term outcome after epilepsy surgery for cortical malformations are rare. In this study, we report our experience with surgical treatment and year to year long term outcome for a subgroup of patients with focal cortical dysplasia (FCD). METHODS: We retrospectively analysed the records of 49 patients (females n = 26; males n = 23; mean age 25 (11) years) with a mean duration of epilepsy of 18 years (range 1-45). Preoperative MRI, histological results based on the Palmini classification and clinical year to year follow-up according to the International League Against Epilepsy (ILAE) classification were available in all patients. RESULTS: 98% of patients had a lesion on preoperative MRI. In addition to lobectomy (n = 9) or lesionectomy (n = 40), 14 patients had multiple subpial transections of the eloquent cortex. The resected tissue was classified as FCD type II b in 41 cases with an extratemporal (88%) and FCD type II a in 8 cases with a temporal localisation (100%). After a mean follow-up of 8.1 (4.5) years, 37 patients (76%) were seizure free, a subgroup of 23 patients (47%) had been completely seizure free since surgery (ILAE class 1a) and 4 patients (8%) had only auras (ILAE class 2). Over a 10 year follow-up, the proportion of satisfactory outcomes decreased, mainly within the first 3 years. During long term follow-up, 48% stopped antiepileptic drug treatment, 34% received a driver's license and 57% found a job or training. CONCLUSION: Surgical treatment of epilepsy with FCD is not only successful in the short term but also has a satisfying long term outcome which remains constant after 3 years of follow up but is not associated with better employment status or improvement in daily living. PMID- 17287240 TI - Visual recognition memory differentiates dementia with Lewy bodies and Parkinson's disease dementia. AB - OBJECTIVE: To compare cognitive impairments in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), to discriminate between the two entities. METHODS: 10 DLB and 12 PDD consecutive patients performed a neuropsychological battery designed to assess several cognitive domains: verbal and visual memory (Delayed Matching to Sample (DMS)-48), language, gnosia, praxia and executive functions. RESULTS: DLB patients had poorer performances in orientation (p<0.05), Trail Making Test A (p<0.05) and reading of names of colours in the Stroop Test (p<0.05). Their scores were also lower in the visual object recognition memory test (DMS-48), in both immediate (p<0.05) and delayed recognition (p<0.05). No differences were observed in the other tests. CONCLUSION: Despite global similarities in cognitive performances between DLB and PDD patients, we observed important differences: in particular, DMS-48, a test of visual object recognition memory and visual storage capacity, was poorer in DLB patients. PMID- 17287241 TI - Eyelid ptosis from sympathetic nerve dysfunction mistaken as myopathy: a simple test to identify this condition. AB - Acquired isolated unilateral or bilateral blepharoptosis has many aetiologies. When the pupils are normal, a myasthenic syndrome or myopathy has to be ruled out. If the tests for myasthenia gravis are negative, the next step is to perform a muscle biopsy to establish a diagnosis. Muscle examination may show a mitochondrial disorder, non-specific abnormalities or be quite normal. We identified three patients, who had previously undergone various investigations, including a muscle biopsy, whose lid ptosis disappeared using eye drops containing naphazoline nitrate, a sympathomimetic drug, thus suggesting partial Horner's syndrome. We emphasise the usefulness of this simple and cheap test before performing more traumatic and expensive investigations. PMID- 17287242 TI - Estimates of the cancer incidence and mortality in Europe in 2006. AB - BACKGROUND: Monitoring the evolution of the cancer burden in Europe is of great value. Estimates of the cancer burden in Europe have been published for 2004 and estimates are now being presented for cancer incidence and mortality in Europe for 2006. METHODS: The most recent sources of cancer incidence and mortality data have been collected and projections have been carried out using short-term prediction methods to produce estimated rates for 2006. Additional estimation was required where national incidence data were not available, and the method involved the projection of the aggregations of cancer incidence and mortality data from representative cancer registries. The estimated 2006 rates were applied to the corresponding estimated country population to obtain the best estimates of the cancer incidence and mortality in Europe in 2006. RESULTS: In 2006 in Europe, there were an estimated 3,191,600 cancer cases diagnosed (excluding nonmelanoma skin cancers) and 1,703,000 deaths from cancer. The most common form of cancers was breast cancer (429,900 cases, 13.5% of all cancer cases), followed by colorectal cancers (412,900, 12.9%) and lung cancer (386,300, 12.1%). Lung cancer, with an estimated 334,800 deaths (19.7% of total), was the most common cause of death from cancer, followed by colorectal (207,400 deaths), breast (131,900) and stomach (118,200) cancers. CONCLUSIONS: The total number of new cases of cancer in Europe appears to have increased by 300,000 since 2004. With an estimated 3.2 million new cases (53% occurring in men, 47% in women) and 1.7 million deaths (56% in men, 44% in women) each year, cancer remains an important public health problem in Europe and the ageing of the European population will cause these numbers to continue to increase even if age-specific rates remain constant. Evidence-based public health measures exist to reduce the mortality of breast and colorectal cancer while the incidence of lung cancer, and several other forms of cancer, could be diminished by improved tobacco control. PMID- 17287243 TI - Contribution of viruses, Chlamydia spp. and Mycoplasma pneumoniae to acute respiratory infections in Iranian children. AB - The study reports the frequency and clinical presentation of respiratory syncytial virus (RSV), human metapneumovirus, influenza (Inf V), parainfluenza, adenovirus (Adv), Chlamydia spp. and Mycoplasma pneumoniae in children with acute respiratory infections (ARI) in Rasht, Iran. Nasopharyngeal aspirates and swabs were collected from 261 children in 2003 and 2004. Pathogens were detected using polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR), confirmed with sequence analysis. Ninety-three pathogens were detected in 83 children. RSV was present in 39 (15%), Adv in 37 (14%), Inf A in 11 (4%), C. trachomatis in 4 (2%) and M. pneumoniae, in 2 (1%) children. Neither parainfluenza nor metapneumovirus were detected. RSV, Inf A and C. trachomatis were more frequent in children with lower respiratory infections. Adv presented more frequently as upper respiratory infection. All pathogens, except M. pneumoniae, were detected in children with severe pneumonia. Viruses play a significant role in Iranian children with community-acquired ARI. PMID- 17287244 TI - Increasing burden of childhood severe malaria in a Nigerian tertiary hospital: implication for control. AB - Malaria remains an important public heath concern in Nigeria because of its impact on child and maternal health, but the contribution of severe malaria to morbidity among Nigerian children was scantly reported. This study was undertaking to document the hospital-burden of severe malaria among children in Ibadan in order to reflect on the impacts and health implications of the current malaria control strategies. A review of 6-year case records of all children admitted to the emergency ward of the University College Hospital Ibadan was carried out. Cases of severe malaria were defined as those children in whom parasitaemia were confirmed with blood film microscopy and any of the WHO case definitions for severe malaria was documented. Severe malaria cases constituted 11.3% of 16 031 admissions (2000-05) with 89.1% being children <5 years old. Cerebral malaria accounted for about one-fifth (19.7%) of all severe malaria cases. The yearly proportional morbidity rate from severe malaria ranged from 8.7% to 13.2% with significant increase from 2000 to 2004 (X2 = 48.49; df = 5; P < 0.001). Severe malaria accounted for 12.4% of all paediatric deaths with an estimated overall case fatality rate of 9.6%. Deaths from malaria were significantly associated with wasting (Z-score for weight-for-height two TAMs > four TAMs = M184V > K65R. In undifferentiated monocytes, WT virus replication could be detected in three of six donors, but replication of all mutant viruses remained undetectable. Altogether, our results confirm that nucleoside reverse transcriptase inhibitors (NRTIs) are powerful antiviral agents in differentiated macrophages, reveal that HIV resistance to some NRTIs may be less efficient in these cells, and indicate that resistance-associated loss of RC is more pronounced in macrophages than in high-dNTP content cell systems. PMID- 17287265 TI - Inhibition of airway Na+ transport by respiratory syncytial virus. AB - In previous studies, we have shown that two major respiratory pathogens, influenza virus and parainfluenza virus, produce acute alterations in ion transport upon contacting the apical membrane of the respiratory epithelium. In the present study, we examine the effects on ion transport by the mouse tracheal epithelium of a third major respiratory pathogen, respiratory syncytial virus (RSV). RSV infections are associated with fluid accumulation in the respiratory tract and cause illnesses that range in severity from rhinitis, sinusitis, otitis media, and bronchitis to bronchiolitis and pneumonia. We find that within minutes of RSV contacting the apical membrane; it inhibits amiloride-sensitive Na+ transport by the epithelium. This effect is mediated by protein kinase C and is reproduced by recombinant viral F (fusion) protein. Since this inhibition is not accompanied by any alteration in the epithelial responses to carbachol or to forskolin plus 3-isobutyl-1-methylxanthine (IBMX), it is not due to a nonspecific toxic action of the virus. The inhibition also appears to require Toll-like receptor 4 and the presence of asialogangliosides in the apical membrane. Since the concentration range over which this inhibition is observed (10(2) to 10(5) PFU/ml) is comparable to the viral concentrations observed in clinical and experimental RSV infections, it seems likely that direct inhibition by the virus of epithelial Na+ transport may contribute to the fluid accumulation that is observed in RSV infections. PMID- 17287266 TI - Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. AB - Dysfunctional CD8+ T cells present in chronic virus infections can express programmed death 1 (PD-1) molecules, and the inhibition of the engagement of PD-1 with its ligand (PD-L1) has been reported to enhance the antiviral function of these T cells. We took advantage of the wide fluctuations in levels of viremia which are typical of chronic hepatitis B virus (HBV) infection to comprehensively analyze the impact of prolonged exposure to different virus quantities on virus specific T-cell dysfunction and on its reversibility through the blocking of the PD-1/PD-L1 pathway. We confirm that chronic HBV infection has a profound effect on the HBV-specific T-cell repertoire. Despite the use of a comprehensive panel of peptides covering all HBV proteins, HBV-specific T cells were rarely observed directly ex vivo in samples from patients with chronic infection, in contrast to those from patients with acute HBV infection. In chronic HBV infection, virus specific T cells were detected mainly in patients with lower levels of viremia. These HBV-specific CD8+ T cells expressed PD-1, and their function was improved by the blocking of PD-1/PD-L1 engagement. Thus, a broad spectrum of anti-HBV immunity is expressed by patients with chronic HBV infection and this spectrum is proportional to HBV replication levels and can be improved by blocking the PD 1/PD-L1 pathway. This information may be useful for the design of immunotherapeutic strategies to complement and optimize available antiviral therapies. PMID- 17287268 TI - Distinct sites on the Sindbis virus RNA-dependent RNA polymerase for binding to the promoters for the synthesis of genomic and subgenomic RNA. AB - Sindbis virus-infected cells make two positive-strand RNAs, a genomic (G) RNA and a subgenomic (SG) RNA. Here we report the amino acid sequence in nonstructural protein 4 (nsP4), the viral RNA-dependent RNA polymerase, that binds to the promoter for the synthesis of G RNA. In addition, using a cell-free system that makes both G and SG RNA, we show that specific amino acid changes in nsP4 that abolish the synthesis of SG RNA have no effect on the synthesis of G RNA. Our findings indicate that nsP4 has distinct sites for the recognition of the G and SG promoters. PMID- 17287267 TI - Multiple roles of Epstein-Barr virus SM protein in lytic replication. AB - The effect of Epstein-Barr virus (EBV) SM protein on EBV gene expression was examined using a recombinant EBV strain with the SM gene deleted and DNA microarrays representing all known EBV coding regions. Induction of lytic EBV replication in the absence of SM led to expression of approximately 40% of EBV genes, but a block in expression of over 50% of EBV genes. Contrary to previous findings, several early genes were SM dependent, and lytic EBV DNA replication did not occur in the absence of SM. Notably, two genes essential for lytic EBV DNA replication, BSLF1 and BALF5, encoding EBV DNA primase and polymerase, respectively, were SM dependent. Lytic DNA replication was partially rescued by ectopic expression of EBV primase and polymerase, but virion production was not. Rescue of DNA replication only enhanced expression of a subset of late genes, consistent with a direct requirement for SM for late gene expression in addition to its contribution to DNA replication. Therefore, while SM is essential for most late gene expression, the proximate block to virion production by the EBV SM deletion strain is an inability to replicate linear DNA. The block to DNA replication combined with the direct effect of SM on late gene expression leads to a global deficiency of late gene expression. SM also inhibited BHRF1 expression during productive replication in comparison to that of cells induced into lytic replication in the absence of SM. Thus, SM plays a role in multiple steps of lytic cycle EBV gene expression and that it is transcript-specific in both activation and repression functions. PMID- 17287269 TI - PATJ, a tight junction-associated PDZ protein, is a novel degradation target of high-risk human papillomavirus E6 and the alternatively spliced isoform 18 E6. AB - The E6 protein from high-risk human papillomavirus types interacts with and degrades several PDZ domain-containing proteins that localize to adherens junctions or tight junctions in polarized epithelial cells. We have identified the tight junction-associated multi-PDZ protein PATJ (PALS1-associated TJ protein) as a novel binding partner and degradation target of high-risk types 16 and 18 E6. PATJ functions in the assembly of the evolutionarily conserved CRB PALS1-PATJ and Par6-aPKC-Par3 complexes and is critical for the formation of tight junctions in polarized cells. The ability of type 18 E6 full-length to bind to, and the subsequent degradation of, PATJ is dependent on its C-terminal PDZ binding motif. We demonstrate that the spliced 18 E6* protein, which lacks a C terminal PDZ binding motif, associates with and degrades PATJ independently of full-length 18 E6. Thus, PATJ is the first binding partner that is degraded in response to both isoforms of 18 E6. The ability of E6 to utilize a non-E6AP ubiquitin ligase for the degradation of several PDZ binding partners has been suggested. We also demonstrate that 18 E6-mediated degradation of PATJ is not inhibited in cells where E6AP is silenced by shRNA. This suggests that the E6 E6AP complex is not required for the degradation of this protein target. PMID- 17287270 TI - Model for T-antigen-dependent melting of the simian virus 40 core origin based on studies of the interaction of the beta-hairpin with DNA. AB - The interaction of simian virus 40 (SV40) T antigen (T-ag) with the viral origin has served as a model for studies of site-specific recognition of a eukaryotic replication origin and the mechanism of DNA unwinding. These studies have revealed that a motif termed the "beta-hairpin" is necessary for assembly of T-ag on the SV40 origin. Herein it is demonstrated that residues at the tip of the "beta-hairpin" are needed to melt the origin-flanking regions and that the T-ag helicase domain selectively assembles around one of the newly generated single strands in a manner that accounts for its 3'-to-5' helicase activity. Furthermore, T-ags mutated at the tip of the "beta-hairpin" are defective for oligomerization on duplex DNA; however, they can assemble on hybrid duplex DNA or single-stranded DNA (ssDNA) substrates provided the strand containing the 3' extension is present. Collectively, these experiments indicate that residues at the tip of the beta-hairpin generate ssDNA in the core origin and that the ssDNA is essential for subsequent oligomerization events. PMID- 17287271 TI - Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1) specific CD8+ T cells after early HIV-1 infection. AB - Human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells in early infection are associated with the dramatic decline of peak viremia, whereas their antiviral activity in chronic infection is less apparent. The functional properties accounting for the antiviral activity of HIV-1-specific CD8+ T cells during early infection are unclear. Using cytokine secretion and tetramer decay assays, we demonstrated in intraindividual comparisons that the functional avidity of HIV-1-specific CD8+ T cells was consistently higher in early infection than in chronic infection in the presence of high-level viral replication. This change of HIV-1-specific CD8+ T-cell avidity between early and chronic infections was linked to a substantial switch in the clonotypic composition of epitope specific CD8+ T cells, resulting from the preferential loss of high-avidity CD8+ T-cell clones. In contrast, the maintenance of the initially recruited clonotypic pattern of HIV-1-specific CD8+ T cells was associated with low-level set point HIV-1 viremia. These data suggest that high-avidity HIV-1-specific CD8+ T-cell clones are recruited during early infection but are subsequently lost in the presence of persistent high-level viral replication. PMID- 17287273 TI - Duplicated sequence motif in the long terminal repeat of maedi-visna virus extends cell tropism and is associated with neurovirulence. AB - Maedi-visna virus (MVV) is a lentivirus of sheep causing chronic inflammatory disease of the lungs (maedi) and the nervous system (visna). We have previously shown that a duplicated sequence in the long terminal repeat (LTR) of MVV is a determinant of cell tropism. Here, we demonstrate that deletion of a CAAAT sequence from either one of the repeats resulted in poor virus growth in sheep choroid plexus cells. A duplication in the LTR encompassing the CAAAT sequence was found in four neurological field cases that were sequenced, but no duplication was present in the LTRs from seven maedi cases; one maedi isolate was mixed. These results indicate that the duplication in the LTR is associated with neurovirulence. PMID- 17287272 TI - An affinity-enhanced neutralizing antibody against the membrane-proximal external region of human immunodeficiency virus type 1 gp41 recognizes an epitope between those of 2F5 and 4E10. AB - The membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 bears the epitopes of two broadly neutralizing antibodies (Abs), 2F5 and 4E10, making it a target for vaccine design. A third Ab, Fab Z13, had previously been mapped to an epitope that overlaps those of 2F5 and 4E10 but only weakly neutralizes a limited set of primary isolates. Here, libraries of Fab Z13 variants displayed on phage were engineered and affinity selected against an MPER peptide and recombinant gp41. A high-affinity variant, designated Z13e1, was isolated and found to be approximately 100-fold improved over the parental Fab not only in binding affinity for the MPER antigens but also in neutralization potency against sensitive HIV-1. Alanine scanning of MPER residues 664 to 680 revealed that N671 and D674 are crucial for peptide recognition as well as for the neutralization of HIV-1 by Z13e1. Ab competition studies and truncation of MPER peptides indicate that Z13e1 binds with high affinity to an epitope between and overlapping with those of 2F5 and 4E10, with the minimal peptide epitope WASLWNWFDITN. Still, Z13e1 remained about an order of magnitude less potent than 4E10 against several isolates of pseudotyped HIV-1. The sum of our molecular analyses with Z13e1 suggests that the segment on the MPER of gp41 between the 2F5 and 4E10 epitopes is exposed on the functional envelope trimer but that access to the specific Z13e1 epitope within this segment is limited. Thus, the ability of MPER-bearing immunogens to elicit potent HIV-1-neutralizing Abs may depend in part on recapitulating the particular constraints that the functional envelope trimer imposes on the segment of the MPER to which Z13e1 binds. PMID- 17287276 TI - Processing of RNAs of the family Avsunviroidae in Chlamydomonas reinhardtii chloroplasts. AB - The family Avsunviroidae comprises four viroid species with the ability to form hammerhead ribozymes that mediate self-cleavage of the multimeric plus and minus strands resulting from replication in the chloroplast through a symmetric rolling circle mechanism. Research on these RNAs is restricted by their host range, which is limited to the plants wherein they were initially identified and some closely related species. Here we report cleavage and ligation in transplastomic Chlamydomonas reinhardtii expressing plus- and minus-strand dimeric transcripts of representative members of the family Avsunviroidae. Despite the absence of viroid RNA-RNA transcription, the C. reinhardtii-based system can be used to address intriguing questions about viroid RNA processing and, in particular, about the cellular factors involved in cleavage and ligation. PMID- 17287274 TI - Molecular characterization of the rhesus rhadinovirus (RRV) ORF4 gene and the RRV complement control protein it encodes. AB - The diversity of viral strategies to modulate complement activation indicates that this component of the immune system has significant antiviral potential. One example is the Kaposi's sarcoma-associated herpesvirus (KSHV) complement control protein (KCP), which inhibits progression of the complement cascade. Rhesus rhadinovirus (RRV), like KSHV, is a member of the subfamily Gammaherpesvirinae and currently provides the only in vivo model of KSHV pathobiology in primates. In the present study, we characterized the KCP homologue encoded by RRV, RRV complement control protein (RCP). Two strains of RRV have been sequenced to date (H26-95 and 17577), and the RCPs they encode differ substantially in structure: RCP from strain H26-95 has four complement control protein (CCP) domains, whereas RCP from strain 17577 has eight CCP domains. Transcriptional analyses of the RCP gene (ORF4, referred to herein as RCP) in infected rhesus macaque fibroblasts mapped the ends of the transcripts of both strains. They revealed that H26-95 encodes a full-length, unspliced RCP transcript, while 17577 RCP generates a full length unspliced mRNA and two alternatively spliced transcripts. Western blotting confirmed that infected cells express RCP, and immune electron microscopy disclosed this protein on the surface of RRV virions. Functional studies of RCP encoded by both RRV strains revealed their ability to suppress complement activation by the classical (antibody-mediated) pathway. These data provide the foundation for studies into the biological significance of gammaherpesvirus complement regulatory proteins in a tractable, non-human primate model. PMID- 17287275 TI - Kaposi's sarcoma-associated herpesvirus induces sustained NF-kappaB activation during de novo infection of primary human dermal microvascular endothelial cells that is essential for viral gene expression. AB - In vitro Kaposi's sarcoma-associated herpesvirus (KSHV) infection of primary human dermal microvascular endothelial (HMVEC-d) cells and human foreskin fibroblast (HFF) cells is characterized by the induction of preexisting host signal cascades, sustained expression of latency-associated genes, transient expression of a limited number of lytic genes, and induction of several cytokines, growth factors, and angiogenic factors. Since NF-kappaB is a key molecule involved in the regulation of several of these factors, here, we examined NF-kappaB induction during de novo infection of HMVEC-d and HFF cells. Activation of NF-kappaB was observed as early as 5 to 15 min postinfection by KSHV, and translocation of p65-NF-kappaB into nuclei was detected by immunofluorescence assay, electrophoretic mobility shift assay, and p65 enzyme linked immunosorbent assay. IkappaB phosphorylation inhibitor (Bay11-7082) reduced this activation significantly. A sustained moderate level of NF-kappaB induction was seen during the observed 72 h of in vitro KSHV latency. In contrast, high levels of ERK1/2 activation at earlier time points and a moderate level of activation at later times were observed. p38 mitogen-activated protein kinase was activated only at later time points, and AKT was activated in a cyclic manner. Studies with UV-inactivated KSHV suggested a role for virus entry stages in NF-kappaB induction and a requirement for KSHV viral gene expression in sustained induction. Inhibition of NF-kappaB did not affect target cell entry by KSHV but significantly reduced the expression of viral latent open reading frame 73 and lytic genes. KSHV infection induced the activation of several host transcription factors, including AP-1 family members, as well as several cytokines, growth factors, and angiogenic factors, which were significantly affected by NF-kappaB inhibition. These results suggest that during de novo infection, KSHV induces sustained levels of NF-kappaB to regulate viral and host cell genes and thus possibly regulates the establishment of latent infection. PMID- 17287277 TI - Induction of endoplasmic reticulum stress in thymic lymphocytes by the envelope precursor polyprotein of a murine leukemia virus during the preleukemic period. AB - Infection of thymic lymphocytes by a mink cell focus-forming murine leukemia virus induces apoptosis during the preleukemic period of lymphomagenesis. In this study, we observed that during this period, the viral envelope precursor polyprotein accumulated to high levels in thymic lymphocytes from mice inoculated with virus. Envelope accumulation occurred with the same kinetics as the induction of endoplasmic reticulum (ER) stress, which resulted in the upregulation of the 78-kDa glucose-regulated protein (GRP78). In thymic lymphomas, GRP78 levels were higher than those in virus-infected preleukemic cells, and GRP58 was upregulated. These results suggest that Env precursor accumulation induces ER stress, which participates in thymic lymphocyte apoptosis. The subsequent upregulation of ER chaperone proteins GRP78 and GRP58 may contribute to rescuing cells from virus-induced apoptosis. PMID- 17287278 TI - Kaposi's sarcoma-associated herpesvirus promotes angiogenesis by inducing angiopoietin-2 expression via AP-1 and Ets1. AB - Infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is required for the development of Kaposi's sarcoma (KS), a highly inflammatory angiogenic tumor of endothelial cells commonly found in untreated AIDS patients. Angiopoietin 2 (Ang 2) modulates the vasculature during inflammation and angiogenesis, but the mechanism by which KSHV regulates Ang-2 expression has not been investigated. Here, we show that KSHV infection of primary human umbilical vein endothelial cells induced the expression and release of Ang-2, which in turn was required for KSHV-induced paracrine-dependent angiogenesis in vivo. Ang-2 was strongly expressed in small vessels and spindle tumor cells in KS tumors. Mechanistically, KSHV activated the Ang-2 promoter via AP-1 and Ets1 transcriptional factors, which were mediated by ERK, JNK, and p38 mitogen-activated protein kinase (MAPK) pathways. Our findings demonstrate the importance of Ang-2 in KS angiogenesis and define a novel role for AP-1 and MAPK pathways in regulating angiogenesis. This study also illustrates a distinct mechanism by which a tumor virus modulates vasculature to promote tumorigenesis and exemplifies the convergence of oncogenesis and angiogenesis pathways in tumor development. PMID- 17287279 TI - Phenotypic and genotypic comparisons of human T-cell leukemia virus type 1 reverse transcriptases from infected T-cell lines and patient samples. AB - It is well established that cell-free infection with human T-cell leukemia virus type 1 (HTLV-1) is less efficient than that with other retroviruses, though the specific infectivities of only a limited number of HTLV-1 isolates have been quantified. Earlier work indicated that a post-entry step in the infectious cycle accounted for the poor cell-free infectivity of HTLV-1. To determine whether variations in the pol gene sequence correlated with virus infectivity, we sequenced and phenotypically tested pol genes from a variety of HTLV-1 isolates derived from primary sources, transformed cell lines, and molecular clones. The pol genes and deduced amino acid sequences from 23 proviruses were sequenced and compared with 14 previously published sequences, revealing a limited number of amino acid variations among isolates. The variations appeared to be randomly dispersed among primary isolates and proviruses from cell lines and molecular clones. In addition, there was no correlation between reverse transcriptase sequence and the disease phenotype of the original source of the virus isolate. HTLV-1 pol gene fragments encoding reverse transcriptase were amplified from a variety of isolates and were subcloned into HTLV-1 vectors for both single-cycle infection and spreading-infection assays. Vectors carrying pol genes that matched the consensus sequence had the highest titers, and those with the largest number of variations from the consensus had the lowest titers. The molecular clone from CS-1 cells had four amino acid differences from the consensus sequence and yielded infectious titers that were approximately eight times lower than those of vectors encoding a consensus reverse transcriptase. PMID- 17287281 TI - The nucleocytoplasmic rabies virus P protein counteracts interferon signaling by inhibiting both nuclear accumulation and DNA binding of STAT1. AB - Rabies virus P protein inhibits alpha interferon (IFN-alpha)- and IFN-gamma stimulated Jak-STAT signaling by retaining phosphorylated STAT1 in the cytoplasm. Here, we show that P also blocks an intranuclear step that is the STAT1 binding to the DNA promoter of IFN-responsive genes. As P is a nucleocytoplasmic shuttling protein, we first investigated the effect of the cellular distribution of P on the localization of STAT1 and consequently on IFN signaling. We show that the localization of STAT1 is correlated with the localization of P: in cells expressing a nuclear form of P (the short P3 isoform or the complete P in the presence of the export inhibitor leptomycin B), STAT1 is nuclear, whereas in cells expressing a cytoplasmic form of P, STAT1 is cytoplasmic. However, the expression of nuclear forms of P inhibits the signaling of both IFN-gamma and IFN alpha, demonstrating that the retention of STAT1 in the cytoplasm is not the only mechanism involved in the inhibition of IFN signaling. Electrophoretic mobility shift analysis indicates that P expression in the cell extracts of infected cells or in stable cell lines prevents IFN-induced DNA binding of STAT1. The loss of the DNA binding of STAT1 and ISGF3 was also observed when purified recombinant P or P3 was added to the extracts of IFN-gamma- or IFN-alpha-treated cells, indicating that P directly affects the DNA binding activity of STAT1. Then products of the rabies virus P gene are able to counteract IFN signaling by creating both cytoplasmic and nuclear blocks for STAT1. PMID- 17287280 TI - Superinfection exclusion in cells infected with hepatitis C virus. AB - Superinfection exclusion is the ability of an established virus infection to interfere with infection by a second virus. In this study, we found that Huh-7.5 cells acutely infected with hepatitis C virus (HCV) genotype 2a (chimeric strain J6/JFH) and cells harboring HCV genotype 1a, 1b, or 2a full-length or subgenomic replicons were resistant to infection with cell culture-produced HCV (HCVcc). Replicon-containing cells became permissive for HCVcc infection after treatment with an HCV-specific protease inhibitor. With the exception of cells harboring a J6/JFH-FLneo replicon, infected or replicon-containing cells were permissive for HCV pseudoparticle (HCVpp) entry, demonstrating a postentry superinfection block downstream of primary translation. The surprising resistance of J6/JFH-FLneo replicon-containing cells to HCVpp infection suggested a defect in virus entry. This block was due to reduced expression of the HCV coreceptor CD81. Further analyses indicated that J6/JFH may be toxic for cells expressing high levels of CD81, thus selecting for a CD81(low) population. CD81 down regulation was not observed in acutely infected cells, suggesting that this may not be a general mechanism of HCV superinfection exclusion. Thus, HCV establishes superinfection exclusion at a postentry step, and this effect is reversible by treatment of infected cells with antiviral compounds. PMID- 17287282 TI - Sulfated homologues of heparin inhibit hepatitis C virus entry into mammalian cells. AB - The mechanism of entry of hepatitis C virus (HCV) through interactions between the envelope glycoproteins and specific cell surface receptors remains unclear at this time. We have previously shown with the vesicular stomatitis virus (VSV)/HCV pseudotype model that the hypervariable region 1 of the HCV E2 envelope glycoprotein helps in binding with glycosaminoglycans present on the cell surface. In this study, we have examined the binding of HCV envelope glycoproteins with chemically modified derivatives of heparin. Furthermore, we have determined the functional relevance of the interaction of heparin derivatives with HCV envelope glycoproteins for infectivity by using a human immunodeficiency virus (HIV)/HCV pseudotype, a VSV/HCV pseudotype, and cell culture-grown HCV genotype 1a. Taken together, our results suggest that the HCV envelope glycoproteins rely upon O-sulfated esters of a heparin homologue to facilitate entry into mammalian cells. PMID- 17287283 TI - The adenovirus E4 ORF3 protein binds and reorganizes the TRIM family member transcriptional intermediary factor 1 alpha. AB - One of the most interesting functions attributed to the adenovirus early region 4 open reading frame 3 (E4 ORF3) protein is its reorganization of promyelocytic leukemia (PML) protein nuclear bodies. These normally punctate structures are reorganized by E4 ORF3 into tracks that eventually surround viral replication centers. PML rearrangement is an evolutionarily conserved function of E4 ORF3, yet its cause and functional relevance remain mysteries. The E4 ORF3 protein coimmunoprecipitates with the PML protein, yet E4 ORF3 still forms tracks in cells that lack PML. The PML protein is a member of a larger protein family termed tripartite motif (TRIM) proteins. TRIM proteins contain a tripartite domain structure in proximity to their N termini that consists of a RING finger domain, followed by one or two B box domains and a C-terminal coiled-coil domain (collectively termed the RBCC domain). The order and spacing of these domains are evolutionarily conserved and thought to mediate protein-protein interactions and other functions. We implemented a proteomic approach to isolate cellular proteins that bind to E4 ORF3. We identified a novel interaction between E4 ORF3 and another TRIM family member, transcriptional intermediary factor 1 alpha (TIF1alpha). TIF1alpha functions by recruiting coactivators and/or corepressors to modulate transcription. The interaction between E4 ORF3 and TIF1alpha was validated by coimmunoprecipitation and binding of recombinant proteins. Indirect immunofluorescence assays demonstrated that TIF1alpha is reorganized into track structures that contain PML upon E4 ORF3 expression. The RBCC domain of TIF1alpha is sufficient for E4 ORF3-induced rearrangement, and TIF1alpha reorganization is conserved across adenovirus serotypes. PMID- 17287284 TI - Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains. AB - In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains. PMID- 17287285 TI - Characterization of a replication-competent, integrase-defective human immunodeficiency virus (HIV)/simian virus 40 chimera as a powerful tool for the discovery and validation of HIV integrase inhibitors. AB - Integrase is actively studied as an antiviral target, but many inhibitors selected from biochemical screens fail to inhibit human immunodeficiency virus (HIV) replication or primarily affect off-site targets. Here we develop and validate a replication-competent, simian virus 40-HIV integrase mutant chimera as a novel tool to classify the mechanism of action of potential integrase inhibitors. Whereas the mutant was more susceptible than the wild type to entry, reverse transcriptase, and protease inhibitors, it specifically resisted the action of integrase inhibitor L-870,810. We furthermore demonstrate inhibition of integration by GS-9137 and GS-9160 and off-site targeting by the 6-aminoquinolone antibiotic WM-5. PMID- 17287286 TI - Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations. AB - We have identified 12 patients with autosomal recessive mitochondrial encephalomyopathy with elevated methylmalonic acid. The disorder has a high incidence of 1 in 1700 in the Faroe Islands due to a founder effect, and a carrier frequency of 1 in 33. The symptoms comprise hypotonia, muscle atrophy, hyperkinesia, severe hearing impairment and postnatal growth retardation. Neuroimaging showed demyelination and central and cortical atrophy, including atrophy of the basal ganglia, and some of the patients fulfilled the criteria for Leigh syndrome. Urine and plasma methylmalonic acid were elevated. Homozygosity mapping with the Affymetrix 10 K array revealed a homozygous region on chromosome 13q14 harbouring the SUCLA2 gene. Mutations in SUCLA2 were recently shown to cause a similar disorder in a small Israeli family. Mutation analysis identified a novel splice site mutation in SUCLA2, IVS4 + 1G --> A, leading to skipping of exon 4. The SUCLA2 gene encodes the ATP-forming beta subunit of the Krebs cycle enzyme succinyl-CoA ligase. The hallmark of the condition, elevated methylmalonic acid, can be explained by an accumulation of the substrate of the enzyme, succinyl-CoA, which in turn leads to elevated methylmalonic acid, because the conversion of methylmalonyl-CoA to succinyl-CoA is inhibited. PMID- 17287287 TI - Specific influences of cerebellar dysfunctions on gait. AB - Cerebellar ataxic gait is characterized by unsteady movements and variable gait patterns. Previous studies have successfully identified pathological changes of balance-related gait parameters. However, it has been difficult to demonstrate deficits of joint coordination and the control of limb dynamics. This has motivated the hypothesis that cerebellar ataxic gait might be affected predominantly by balance impairments. We investigated the influences of different types of cerebellar dysfunction on the gait patterns of patients suffering from degenerative cerebellar disease (13 patients, five females, 50.4 +/- 14.4 years). Walking patterns were quantitatively analysed combining standard gait measures and novel measures for the characterization of the spatial and the temporal variability of intra-joint coordination patterns. The temporal variability of gait patterns was significantly correlated with a subscale of the clinical ataxia scale (ICARS) that rates deficits of the control of limb dynamics and intra-limb coordination for goal-directed movements. This suggests that common cerebellar mechanisms might be involved in coordination during voluntary limb control and ataxic gait. The tested standard gait parameters correlated predominantly with clinical measures for balance-related abnormalities. These results imply that ataxic gait is influenced by both balance-related impairments and deficits related to limb control and intra-limb coordination. Applying the same analysis to gait patterns from patients with peripheral vestibular failure (six patients, four females, 47.8 +/- 14.3 years) and Parkinson's disease (eight patients, two females, 60.7 +/- 10.6 years), we found comparable abnormalities in balance related gait parameters and general gait variability, but significantly lower increases of temporal variability. This implies that increased temporal variability of intra-limb coordination is a specific characteristic of cerebellar dysfunction, which does not arise for other movement disorders that also cause balance deficits and increased gait variability. PMID- 17287288 TI - Dual priming oligonucleotide system for the multiplex detection of respiratory viruses and SNP genotyping of CYP2C19 gene. AB - Successful PCR starts with proper priming between an oligonucleotide primer and the template DNA. However, the inevitable risk of mismatched priming cannot be avoided in the currently used primer system, even though considerable time and effort are devoted to primer design and optimization of reaction conditions. Here, we report a novel dual priming oligonucleotide (DPO) which contains two separate priming regions joined by a polydeoxyinosine linker. The linker assumes a bubble-like structure which itself is not involved in priming, but rather delineates the boundary between the two parts of the primer. This structure results in two primer segments with distinct annealing properties: a longer 5' segment that initiates stable priming, and a short 3'-segment that determines target-specific extension. This DPO-based system is a fundamental tool for blocking extension of non-specifically primed templates, and thereby generates consistently high PCR specificity even under less than optimal PCR conditions. The strength and utility of the DPO system are demonstrated here using multiplex PCR and SNP genotyping PCR. PMID- 17287289 TI - Rapid coupling of Surface Plasmon Resonance (SPR and SPRi) and ProteinChip based mass spectrometry for the identification of proteins in nucleoprotein interactions. AB - We compared coupling approaches of SPR to LC-MS and ProteinChip-based mass spectrometry (SELDI) as a means of identifying proteins captured on DNA surfaces. The approach we outline has the potential to allow multiple, quantitative analysis of macromolecular interactions followed by rapid mass spectrometry identification of retained material. PMID- 17287290 TI - Exocyclic amino groups of flanking guanines govern sequence-dependent adduct conformations and local structural distortions for minor groove-aligned benzo[a]pyrenyl-guanine lesions in a GG mutation hotspot context. AB - The environmental carcinogen benzo[a]pyrene (BP) is metabolized to reactive diol epoxides that bind to cellular DNA by predominantly forming N2-guanine adducts (G*). Mutation hotspots for these adducts are frequently found in 5'- ... GG ... dinucleotide sequences, but their origins are poorly understood. Here we used high resolution NMR and molecular dynamics simulations to investigate differences in G* adduct conformations in 5'- ... CG*GC ... and 5'- ... CGG* C... sequence contexts in otherwise identical 12-mer duplexes. The BP rings are positioned 5' along the modified strand in the minor groove in both cases. However, subtle orientational differences cause strong distinctions in structural distortions of the DNA duplexes, because the exocyclic amino groups of flanking guanines on both strands compete for space with the BP rings in the minor groove, acting as guideposts for placement of the BP. In the 5'- ... CGG* C ... case, the 5' flanking G . C base pair is severely untwisted, concomitant with a bend deduced from electrophoretic mobility. In the 5'- ... CG*GC ... context, there is no untwisting, but there is significant destabilization of the 5'-flanking Watson Crick base pair. The minor groove width opens near the lesion in both cases, but more for 5'- ... CGG*C.... Differential sequence-dependent removal rates of this lesion result and may contribute to the mutation hotspot phenomenon. PMID- 17287291 TI - Motif programming: a microgene-based method for creating synthetic proteins containing multiple functional motifs. AB - The presence of peptide motifs within the proteins provides the synthetic biologist with the opportunity to fabricate novel proteins through the programming of these motifs. Here we describe a method that enables one to combine multiple peptide motifs to generate a combinatorial protein library. With this method, a set of sense and antisense oligonucleotide primers were prepared. These primers were mixed and polymerized, so that the resultant DNA consisted of combinatorial polymers of multiple microgenes created from the stochastic assembly of the sense and antisense primers. With this motif-mixing method, we prepared a protein library from the BH1-4 motifs shared among Bcl-2 family proteins. Among the 41 clones created, 70% of clones had a stable, presumably folded expression product in human cells, which was detectable by immunohistochemistry and western blot. The proteins obtained varied with respect to both the number and the order of the four motifs. The method enables homology independent polymerization of DNA blocks that coded motif sequences, and the frequency of each motif within a library can be adjusted in a tailor-made manner. This motif programming has a potential for creating a library with a large proportion of folded/functional proteins. PMID- 17287292 TI - Small ncRNA transcriptome analysis from kinetoplast mitochondria of Leishmania tarentolae. AB - Gene expression in mitochondria of kinetoplastid protozoa requires RNA editing, a post-transcriptional process which involves insertion or deletion of uridine residues at specific sites within mitochondrial pre-mRNAs. Sequence specificity of the RNA editing process is mediated by oligo-uridylated small, non-coding RNAs, designated as guide RNAs (gRNAs). In this study, we have analyzed the small ncRNA transcriptome from kinetoplast mitochondria of Leishmania tarentolae by generating specialized cDNA libraries encoding size-selected RNA species. Through this screen, a significant number of novel oligo-uridylated RNA species, which we have termed oU-RNAs, has been identified. Most novel oU-RNAs are present as stable RNA species in mitochondria as assessed by northern blot analysis. Thereby, novel oU-RNAs show similar expression levels and sizes as previously reported for canonical gRNAs. Several oU-RNAs are transcribed from both strands of the maxicircle and minicircles components of the mitochondrial genome, from regions where up till now no transcription has been reported. Two stable oU-RNAs exhibit an anchor sequence in antisense orientation to known gRNAs and thus might regulate editing of respective pre-mRNAs. A number of oU-RNAs map in antisense orientation to non-edited protein-coding genes suggesting that they might function by a different mechanism. In addition, our screen shows that all kinetoplast-derived RNAs are prone to some degree of uridylation. PMID- 17287293 TI - Quantitative and mechanism-based investigation of post-nuclear delivery events between adenovirus and lipoplex. AB - Quantitative and mechanism-based information on differences in transfection efficiency between viral and non-viral vectors would be highly useful for improving the effectiveness of non-viral vectors. A previous quantitative comparison of intracellular trafficking between adenovirus and LipofectAMINE PLUS (LFN) revealed that the three orders of magnitude lower transfection efficiency of LFN was dominantly rate limited by the post-nuclear delivery process. In the present study, the contribution of transcription and translation processes to the overall differences in the transgene expression efficiency of nucleus-delivered DNA was independently evaluated by quantifying mRNA. As a result, transcription efficiency (E(transcript)) of LFN, denoted as transgene expression divided by the amount of nuclear pDNA was about 16 times less than that for adenovirus. Furthermore, translation efficiency (E(translate)), denoted as transfection activity divided by mRNA expression was approximately 460 times less in LFN. Imaging of the decondensed form of DNA by in situ hybridization revealed that poor decondensation efficiency of LFN is involved in the inferior E(transcript). Moreover, the inferior translation efficiency (E(translate)) of LFN was mainly due to electrostatic interactions between LFN and mRNA. Collectively, an improvement in nuclear decondensation and the diminution of the interaction between vector and mRNA is essential for the development of new generations of non-viral vectors. PMID- 17287296 TI - Chimmitecan, a novel 9-substituted camptothecin, with improved anticancer pharmacologic profiles in vitro and in vivo. AB - PURPOSE: This study aimed to evaluate antitumor activities and pharmacologic profiles of chimmitecan, a novel 9-small-alkyl-substituted lipophilic camptothecin, in comparison with irinotecan (CPT-11) and topotecan. EXPERIMENTAL DESIGN: The in vitro cytotoxities of chimmitecan in human tumor cell lines and multidrug resistance (MDR) cells were evaluated by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide and sulforhodamin B assays. DNA relaxation, cleavage assays, and cellular band depletion assay were combined to delineate its effects on topoisomerase I. DNA damage, cell cycle arrest, and apoptosis were assessed using comet assay, flow cytometry, and DNA ladder analysis, respectively. The in vivo antitumor activities were measured in nude mice bearing human tumor xenografts. RESULTS: Chimmitecan displayed more potent cytotoxicity than SN38 and topotecan. Neither a cross-resistance to chimmitecan in MDR cells nor an influence of human serum albumin in its cytotoxity was observed. Chimmitecan exhibited comparable effects on topoisomerase I compared with the reference drugs, including inhibiting topoisomerase I catalytic activity and trapping and stabilizing covalent topoisomerase I-DNA complexes. Furthermore, nanomolar levels of chimmitecan caused impressive DNA damage, G(2)-M phase arrest, and apoptosis in human leukemia HL60 cells. I.v. administration of chimmitecan inhibited the growth of HCT-116, MDA-MB-435, BEL-7402, and A549 human carcinoma xenografts in nude mice, with greater potency than CPT-11 against the latter two tumors models. Chimmitecan presented potent efficacy in A549 tumor model when given orally. CONCLUSIONS: Chimmitecan is a potent inhibitor of topoisomerase I and displays outstanding activity in vitro and in vivo. The substitution at the 9-position benefits chimmitecan a salient anti-MDR activity, stability in human serum albumin, improved solubility, and oral availability, which might favorably promise its therapeutic potential in clinical settings. PMID- 17287294 TI - Rabies virus matrix protein interplay with eIF3, new insights into rabies virus pathogenesis. AB - Viral proteins are frequently multifunctional to accommodate the high density of information encoded in viral genomes. Matrix (M) protein of negative-stranded RNA viruses such as Rhabdoviridae is one such example. Its primary function is virus assembly/budding but it is also involved in the switch from viral transcription to replication and the concomitant down regulation of host gene expression. In this study we undertook a search for potential rabies virus (RV) M protein's cellular partners. In a yeast two-hybrid screen the eIF3h subunit was identified as an M-interacting cellular factor, and the interaction was validated by co immunoprecipitation and surface plasmon resonance assays. Upon expression in mammalian cell cultures, RV M protein was localized in early small ribosomal subunit fractions. Further, M protein added in trans inhibited in vitro translation on mRNA encompassing classical (Kozak-like) 5'-UTRs. Interestingly, translation of hepatitis C virus IRES-containing mRNA, which recruits eIF3 via a different noncanonical mechanism, was unaffected. Together, the data suggest that, as a complement to its functions in virus assembly/budding and regulation of viral transcription, RV M protein plays a role in inhibiting translation in virus-infected cells through a protein-protein interaction with the cellular translation machinery. PMID- 17287295 TI - Eukaryotic ribosomal protein RPS25 interacts with the conserved loop region in a dicistroviral intergenic internal ribosome entry site. AB - The intergenic region-internal ribosome entry site (IGR-IRES) of dicistroviruses binds to 40S ribosomal subunits in the absence of eukaryotic initiation factors (eIFs). Although the conserved loop sequences in dicistroviral IGR-IRES elements are protected from chemical modifications in the presence of the 40S subunit, molecular components in the 40S subunit, which interacts with the loop sequences in the IRES, have not been identified. Here, a chemical crosslinking study using 4-thiouridine-labeled IGR-IRES revealed interactions of the IGR-IRES with several 40S proteins but not with the 18S rRNA. The strongest crosslinking signal was identified for ribosomal protein S25 (rpS25). rpS25 is known to be a neighbor of rpS5, which has been shown to interact with a related IGR-IRES by cryo-electron microscopy. Crosslinking analysis with site-directed mutants showed that nucleotides UU(6089-6090), which are located in the loop region in conserved domain 2b in the IRES, appear to interact with rpS25. rpS25 is specific to eukaryotes, which explains why there is no recognition of the IGR-IRES by prokaryotic ribosomes. Although the idea that the IGR-IRES element may be a relict of a primitive translation system has been postulated, our experimental data suggest that the IRES has adapted to eukaryotic ribosomal proteins. PMID- 17287297 TI - Dipeptidyl peptidase 8/9-like activity in human leukocytes. AB - The proline-specific dipeptidyl peptidases (DPPs) are emerging as a protease family with important roles in the regulation of signaling by peptide hormones. Inhibitors of DPPs have an intriguing, therapeutic potential, with clinical efficacy seen in patients with diabetes. Until now, only recombinant forms of DPP8 and DPP9 have been characterized. Their enzymatic activities have not been demonstrated in or purified from any natural source. Using several selective DPP inhibitors, we show that DPP activity, attributable to DPP8/9 is present in human PBMC. All leukocyte types tested (lymphocytes, monocytes, Jurkat, and U937 cells) were shown to contain similar DPP8/9-specific activities, and DPPII- and DPPIV specific activities varied considerably. The results were confirmed by DPPIV/CD26 immunocapture experiments. Subcellular fractionation localized the preponderance of DPP8/9 activity to the cytosol and DPPIV in the membrane fractions. Using Jurkat cell cytosol as a source, a 30-fold, enriched DPP preparation was obtained, which had enzymatic characteristics closely related to the ones of DPP8 and/or -9, including inhibition by allo-Ile-isoindoline and affinity for immobilized Lys-isoindoline. PMID- 17287299 TI - Development and validation of database indexes of asthma severity and control. AB - BACKGROUND: The use of administrative databases to perform epidemiological studies in asthma has increased in recent years. The absence of clinical parameters to measure the level of asthma severity and control is a major limitation of database studies. A study was undertaken to develop and validate two database indexes to measure the control and severity of asthma. METHODS: Database indexes of asthma severity and control were derived from definitions in the Canadian Asthma Consensus Guidelines based on dispensed prescriptions and on medical services recorded in two large administrative databases from the Canadian province of Quebec (Regie de l'Assurance Maladie du Quebec (RAMQ) and MED-ECHO) over 12 months. The database indexes of asthma severity and control were validated against the pulmonary function test results of 71 patients with asthma randomly selected from two asthma clinics, and they were also applied to a cohort of patients with asthma followed up for 139 283 person-years selected from the RAMQ and MED-ECHO databases between 1 January 1997 and 31 December 2004. RESULTS: According to the database indexes, 49.3%, 29.6% and 21.1% of patients recruited at the asthma clinics were found to have mild, moderate and severe asthma, respectively, while 53.5% were found to have controlled asthma. The mean predicted value of the forced expiratory volume in 1 s (FEV(1)) ranged from 89.8% for mild asthma to 61.5% for severe asthma (p<0.001), whereas the range from controlled to uncontrolled asthma was 89.5% to 67.3% (p<0.001). The ratio of the FEV(1) to the forced vital capacity (FEV(1)/FVC ratio) measured in 56 patients ranged from 75.8% for mild asthma to 61.8% for severe asthma (p = 0.030), whereas the range from controlled to uncontrolled asthma was 75.3% to 65.7% (p<0.001). CONCLUSION: In the absence of clinical data, these database indexes could be used in epidemiological studies to assess the severity and control of asthma. PMID- 17287298 TI - Patients with ARDS show improvement but not normalisation of alveolar surface activity with surfactant treatment: putative role of neutral lipids. AB - BACKGROUND: Extensive biochemical and biophysical changes of the pulmonary surfactant system occur in the acute respiratory distress syndrome (ARDS). METHODS: The effect of intrabronchial administration of a recombinant surfactant protein C-based surfactant preparation (Venticute) on gas exchange, surfactant composition and function was investigated in 31 patients with ARDS in a randomised controlled phase I/II clinical pilot trial. Bronchoalveolar lavage fluids for surfactant analysis were obtained 3 h before and 48 and 120 h after the first surfactant application. Potentially deleterious effects of surfactant neutral lipids in patients with ARDS were also identified. RESULTS: Before treatment all patients had marked abnormalities in the surfactant phospholipid and protein composition. In response to surfactant treatment, gas exchange improved and surfactant phospholipid and protein content were almost normalised. Alveolar surface activity was dramatically impaired before treatment and only partially improved after surfactant administration. Further analysis of the bronchoalveolar lavage fluids revealed a twofold increase in neutral lipid content and altered neutral lipid profile in patients with ARDS compared with healthy controls. These differences persisted even after administration of large amounts of Venticute. Supplementation of Venticute or natural surfactant with a synthetic neutral lipid preparation, mimicking the profile in ARDS, caused a dose dependent deterioration of surface activity in vitro. CONCLUSION: Intrabronchial surfactant treatment improves gas exchange in ARDS, but the efficacy may be limited by increased concentration and altered neutral lipid profile in surfactant under these conditions. PMID- 17287300 TI - Demographic features, BMPR2 status and outcomes in distal chronic thromboembolic pulmonary hypertension. AB - BACKGROUND: Although pulmonary endarterectomy (PEA) is potentially curative in chronic thromboembolic pulmonary hypertension (CTEPH), some patients have distally distributed disease that is not amenable to surgery. The aetiology and characteristics of this patient group are currently not well understood. OBJECTIVES: This study compares the baseline demographic features and outcomes in subjects with distal CTEPH, those with proximal CTEPH and those with idiopathic pulmonary arterial hypertension (IPAH) to determine whether these conditions represent separate entities or whether they exist along the same spectrum of disease. METHODS: The medical history, clinical characteristics, bone morphogenetic protein receptor type II (BMPR2) mutation status and outcomes of 96 subjects with IPAH, 35 with distal CTEPH and 68 with proximal CTEPH referred to a single specialist centre between 1994 and 2005 were reviewed. RESULTS: There were significant differences between the distal CTEPH, proximal CTEPH and IPAH groups in age (55.9 years vs 54.8 years vs 46.2 years, p<0.001), proportion who were male (43% vs 69% vs 29%, p<0.001), previous deep vein thrombosis (28.6% vs 30.9% vs 3.1%, p<0.001), positive BMPR2 status (0% vs 0% vs 15%, p = 0.018), mean pulmonary artery pressure (47.3 mm Hg vs 45.4 mm Hg vs 54.8 mm Hg, p<0.001) and total pulmonary resistance (12.9 WU vs 12.4 WU vs 18.1 WU, p<0.001). Patients with distal CTEPH and those with IPAH were managed similarly and had comparable survival characteristics (1 year survival 77% vs 86%; 3 year survival 53% vs 60%; p = 0.68). CONCLUSIONS: Patients with distal CTEPH share certain demographic features with patients with proximal CTEPH that not only indicate a common aetiology but also help to differentiate them from patients with IPAH. Despite more favourable haemodynamic parameters in those with distal CTEPH, patients in this group had a poor long-term outcome which was similar to that of patients with IPAH. PMID- 17287301 TI - Sarcopaenia in chronic obstructive pulmonary disease. PMID- 17287303 TI - Screening for lung cancer: yet another problem. PMID- 17287302 TI - Chronic obstructive pulmonary disease exacerbation and risk of pulmonary embolism. PMID- 17287304 TI - Further evidence that the wealthier are healthier: negative life events and asthma-specific quality of life. PMID- 17287306 TI - Computed tomography and cystic fibrosis: promises and problems. AB - Computed tomography (CT) has two potential roles in the evaluation of patients with cystic fibrosis (CF) lung disease: as a diagnostic test primarily for the detection of supervening complications and as a monitoring tool in clinical research. Interest in the latter role has gained momentum in the last 5 years because of two factors: (1) therapeutic options for CF lung disease are developing rapidly, hence the need for an outcome measure that can be applied in clinical intervention trials; and (2) it has become clear that traditional outcome measures such as pulmonary function tests are relatively insensitive to the early structural damage that occurs in CF. Several recent studies have shown that CT can be used as a potential surrogate outcome measure, although its suitability for this specific role is controversial and still under investigation. This review summarises current concepts relating to the research applications of CT in CF, with particular emphasis on the evidence supporting the use of CT as a surrogate outcome measure in clinical trials. PMID- 17287305 TI - Population screening for lung cancer using computed tomography, is there evidence of clinical effectiveness? A systematic review of the literature. AB - Lung cancer is the leading cause of death among all cancer types in the UK, killing approximately 34 000 people per year. By the time symptoms develop, the tumour is often at an advanced stage and the prognosis is bleak. Treatment at a less advanced stage of disease by surgical resection has been shown to substantially reduce mortality. Screening would be attractive if it could detect presymptomatic lung cancer at a stage when surgical intervention is feasible but has been the subject of scientific debate for the past three decades. The aim of this review was to examine the current evidence on the clinical effectiveness of screening for lung cancer using computed tomography. A systematic literature review searching 15 electronic databases and Internet resources from 1994 until December 2004/January 2005 was carried out. Information was summarised narratively. A total of 12 studies of computed tomography screening for lung cancer were identified including two RCTs and 10 studies of screening without comparator groups. The two RCTs were of short duration (1 year). None examined the effect of screening on mortality compared with no screening. The proportion of people with abnormal computed tomography findings varied widely between studies (5-51%). The prevalence of lung cancer detected was between 0.4% and 3.2% (number needed to screen to detect one lung cancer = 31 to 249). Incidence rates of lung cancer were lower (0.1-1%). Among the detected tumours, a high proportion were stage I or resectable tumours, 100% in some studies. Currently, there is insufficient evidence that computed tomography screening is clinically effective in reducing mortality from lung cancer. PMID- 17287307 TI - A chronic pneumothorax and fitness to fly. AB - According to Boyle's law, as the pressure falls, the volume of gas rises in an inversely proportional manner. This means that during an aircraft flight, the volume of trapped air in gas filled body chambers will increase. As a consequence, it is fairly well established that individuals with an untreated pneumothorax should not participate in commercial flying due to the risk of it enlarging and the possible development of tension. However, whether this also applies to individuals who have a long-standing, clinically stable pneumothorax is uncertain. The following article describes two adult patients each with a chronic pneumothorax who asked whether they would be fit to fly in an aircraft. We outline their histories and subsequent evaluation which consisted of clinical assessment, computed tomographic imaging, a hypoxic challenge test and exposure to a hypoxic hypobaric environment in a decompression chamber. PMID- 17287308 TI - When in doubt should we cut it out? The role of surgery in non-small-cell lung cancer. PMID- 17287309 TI - Prevalence of non-cancer-related abnormalities on low-dose spiral computer tomography versus chest radiograph in a screening population. PMID- 17287310 TI - Multiple thoracic osteophytes presenting as mediastinal mass. PMID- 17287311 TI - Traditional Chinese medicine--is the grass always greener? PMID- 17287312 TI - Avidity of the immunoglobulin G response to a Neisseria meningitidis group C polysaccharide conjugate vaccine as measured by inhibition and chaotropic enzyme linked immunosorbent assays. AB - Antibody avidity, the strength of the multivalent interaction between antibodies and their antigens, is an important characteristic of protective immune responses. We have developed an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antibody avidity for the capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC) and determined the avidity constants (K(D)s) for 100 sera from children immunized with an MnC PS conjugate vaccine. The avidity constants were compared to the avidity indices (AI) obtained for the same sera using a chaotropic ELISA protocol. After the primary immunization series, the geometric mean (GM) K(D) was 674 nM and did not change in the months following immunization. However, the GM avidity did increase after the booster dose (GM K(D), 414 nM 1 month after booster immunization). In contrast, the GM AI increased from an initial value of 118 after the primary immunization series to 147 6 months after the completion of the primary immunization series and then further increased to 178 after booster immunization. At the individual subject level, the avidity constant and AI correlated after the primary immunization series and after booster immunization but not prior to boosting. This work suggests that the AI, as measured by the chaotropic ELISA, in contrast to the K(D), reflects changes that render antibody populations less susceptible to disruption by chaotropic agents without directly affecting the strength of the binding interactions. PMID- 17287313 TI - Immunogenicity, reactogenicity, and immune memory after primary vaccination with a novel Haemophilus influenzae-Neisseria meningitidis serogroup C conjugate vaccine. AB - We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [www.ClinicalTrials.gov]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM(197) plus DTPa HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharide challenge with meningococcal polysaccharide C plus a DTPa-HBV-IPV/Hib booster. Immune responses were assessed 1 month after dose 2, 1 month after dose 3, and prior to and 1 month after the booster. After primary vaccination, there was no difference between groups in seroprotection rates as measured by titers of serum bactericidal antibody (SBA) to MenC (> or = 1:8) or concentrations of anti polyribosyl ribitol phosphate (PRP) antibody (> or = 0.15 microg/ml). Prior to the booster, there was no difference between groups in SBA seroprotection rates, whereas anti-PRP seroprotection rates were significantly higher after priming with Hib-MenC-TT. Booster doses induced large increases in SBA and anti-PRP antibodies in primed groups, indicating successful priming with induction of immune memory. Reactogenicity and safety were similar in all groups during the primary and booster phases. A novel combined Hib-MenC-TT conjugate vaccine induced MenC and Hib responses comparable to those induced by licensed monovalent vaccines. A Hib-MenC-TT conjugate vaccine provides vaccination against two major pathogens in a single injection and is a suitable candidate for use in primary or booster vaccination schedules. PMID- 17287314 TI - Generation and characterization of monoclonal antibodies against dengue virus type 1 for epitope mapping and serological detection by epitope-based peptide antigens. AB - Dengue virus (DEN), the pathogen behind dengue hemorrhagic fever, remains a public health problem in Asia and South America. In this study, monoclonal antibodies (MAbs) against DEN serotype 1 (DEN-1) were generated by fusing NSI/1 Ag4-1 mouse myeloma cells with lymphocytes from BALB/c mice immunized with DEN-1. Twelve MAbs were found to react specifically to the DENs by enzyme-linked immunosorbent assay, immunofluorescence analysis, and immunoblotting analysis. Five MAbs, namely, DA4-7, DA6-7, DA9-5, DA10-2, and DA11-13, were found to react with envelope proteins of DEN-1. Two serotype-specific MAbs of DEN-1, DA6-7 and DA11-13, were further shown to neutralize DEN-1 infection by a plaque reduction neutralization test. The neutralizing epitopes of these MAbs were further identified from a random peptide library displayed on phage. Immunopositive phage clones reacted specifically with these MAbs and did not react with normal mouse serum. Epitope-based peptide antigens were proved able to detect antibodies in serum samples collected from DEN-1-infected patients but not in those taken from DEN-2-infected patients or healthy controls. We believe that these MAbs and neutralizing epitopes will provide information that will lead to the development of DEN-1 serotype-specific diagnostic reagents and vaccines. PMID- 17287315 TI - An immunomagnetic single-platform image cytometer for cell enumeration based on antibody specificity. AB - Simplification of cell enumeration technologies is necessary, especially for resource-poor countries, where reliable and affordable enumeration systems are greatly needed. In this paper, an immunomagnetic single-platform image cytometer (SP ICM) for cell enumeration based on antibody specificity is reported. A chamber/magnet assembly was designed such that the immunomagnetically labeled, acridine orange-stained cells in a blood sample moved to the surface of the chamber, where a fluorescent image was captured and analyzed for cell enumeration. The system was evaluated by applying one kind of antibody to count leukocytes and one kind for each leukocyte subpopulation: CD45 for leukocytes, CD3 for T lymphocytes, and CD19 for B lymphocytes. Excellent precision and linearity were achieved. Moreover, these cell counts, each from blood specimens of 42 to 52 randomly selected patients, were compared with those obtained by SP (TruCount) and dual-platform (DP) flow cytometry (FCM) technologies. The cell counts obtained by our system were in between those obtained from the TruCount and DP FCM methods; and good correlations were achieved (R > or = 0.95). For CD4(+) counts, as we expected, the cell count by our system was significantly higher than the CD4(+) T-lymphocyte counts obtained by SP and DP FCM methods. Immunophenotyping of the immunomagnetically selected CD4(+) cells showed that, besides CD4(+) T lymphocytes, a proportion of the CD4(+) dim monocytes was also selected. Our system is a simple immunomagnetic SP ICM, which can potentially be used for enumeration of CD3(+) CD4(+) T lymphocytes in resource-poor countries if an additional CD3 immunofluorescent label is applied. PMID- 17287316 TI - Immunoblot assay using recombinant antigens as a supplemental test to confirm the presence of antibodies to Trypanosoma cruzi. AB - The diagnosis of chronic Chagas' disease is generally made by detecting antibodies to Trypanosoma cruzi. Most conventional serological tests are based on lysates of whole parasites or semipurified antigen fractions from T. cruzi epimastigotes grown in culture. The occurrence of inconclusive and false-positive results has been a persistent problem with the conventional assays, and there is no universally accepted gold standard for confirmation of positive test results. We describe here an immunoblot assay for detecting antibodies to T. cruzi in which four chimeric recombinant antigens (rAgs), designated FP3, FP6, FP10, and TcF, are used as target antigens. Each of these rAgs is composed of several antigenically distinct regions and includes repetitive as well as nonrepetitive sequences. Each rAg is coated as a discrete line on a nitrocellulose strip. Assay sensitivity was assessed by testing 345 specimens known to be positive for antibodies to T. cruzi. All 345 of these samples showed two to four reactive test bands in addition to the three on-board control bands that are on each strip. Assay specificity was determined by testing 500 specimens from random U.S. blood donors, all of which gave negative results. Based on the results obtained in this study, we propose the following scheme for interpretation of test results: (i) no bands or a single test band = a negative result; (ii) two or more test bands with at least one band showing intensity of 1+ or higher = a positive result; and (iii) multiple faint test bands (+/-) = indeterminate result. Based on this scheme, the prototype immunoblot assay showed sensitivity of 100% (n = 345) and specificity of 100% (n = 500). Additionally, all 269 potentially cross-reacting and T. cruzi antibody-negative specimens tested negative in our immunoblot assay. The rAg-based immunoblot assay has potential as a supplemental test for confirming the presence of antibodies to T. cruzi in blood specimens and for identifying false-positive results obtained with other assays. PMID- 17287318 TI - Real-time PCR assay using specimens on filter disks as a template for detection of cytomegalovirus in urine. AB - Since congenital cytomegalovirus (CMV) infection causes late-onset sequelae, the identification of CMV-infected newborns is important. For this purpose, we established a simple real-time PCR assay using a filter disk. Combined with the collection of urine using filter papers placed in the diaper, this assay can make CMV screening more feasible and cost-effective. PMID- 17287317 TI - Development of a sensitive and specific enzyme-linked immunosorbent assay based on recombinant antigens for rapid detection of antibodies against Mycoplasma agalactiae in sheep. AB - We developed a new recombinant enzyme-linked immunosorbent assay (rELISA) for serodiagnosis of contagious agalactia (CA), a disease caused by Mycoplasma agalactiae in sheep and goats. The assay is based on two M. agalactiae surface proteins, namely, P80 and P55. Identification of these immunodominant and common antigens was accomplished by examining the antibody response elicited in sheep during experimental infection and comparing it to the protein expression profiles of 75 M. agalactiae field strains. Our rELISA was tested with 343 sera, collected from sheep with a laboratory-confirmed diagnosis of CA (n = 223) and from healthy animals (n = 120). All sera had previously been tested by Western blotting (WB) for reactivity against M. agalactiae. In addition, our rELISA was compared with a commercial routine ELISA based on inactivated antigens (CHEKiT). Among the 223 samples that were WB positive for M. agalactiae, 209 (93.7%) tested positive for rP80-P55 with our ELISA, whereas only 164 (73.8%) tested positive with the CHEKiT ELISA. Among the 120 samples tested that were WB negative for M. agalactiae, 96.7% were confirmed as negative with our rELISA, while only 75.8% were confirmed as negative with the CHEKiT ELISA. A comparison of the results with receiver operating characteristic curves indicated that the differences observed between our rELISA and the CHEKiT ELISA are statistically significant. The use of recombinant peptides instead of inactivated antigens could significantly improve the discrimination of positive and negative animals, bringing significant advantages in controlling the import/export of live animals and helping in eradication of this economically detrimental disease. PMID- 17287319 TI - The operon encoding SubAB, a novel cytotoxin, is present in shiga toxin-producing Escherichia coli isolates from the United States. PMID- 17287320 TI - Controlled evaluation of the IDI-MRSA assay for detection of colonization by methicillin-resistant Staphylococcus aureus in diverse mucocutaneous specimens. AB - Rapid and reliable detection of methicillin-resistant Staphylococcus aureus (MRSA) carriers is crucial for the effective control of MRSA transmission in healthcare facilities. The aim of this study was to verify the performance of the IDI-MRSA real-time PCR assay for direct MRSA detection in diverse mucocutaneous swabs from hospitalized patients. Swabs from nares (n = 522) and skin or other superficial sites (n = 478) were prospectively collected for MRSA screening from 466 patients admitted to an 858-bed teaching hospital. Swabs were inoculated onto selective chromogenic MRSA-ID agar, buffer extraction solution for IDI-MRSA assay, and enrichment broth. MRSA was detected by culture in 100 specimens from 47 patients. Compared to enrichment culture, the sensitivity and specificity of the PCR assay were 81.0 and 97.0%, respectively, and its positive and negative predictive values were 75.0 and 97.9%, respectively. The IDI-MRSA assay was more sensitive on swabs from nares (90.6%) than from other body sites (76.5%, P < 0.01). The PCR assay detected MRSA in 42 of 47 patients with culture positive study samples. Of 26 patients with culture-negative but PCR-positive study samples, 11 were probable true MRSA carriers based on patient history and/or positive culture on a new sample. The median turnaround time for PCR results was 19 h versus 3 days for agar culture results and 6 days for enrichment culture results. These data confirm the value of IDI-MRSA assay for rapid screening of MRSA mucocutaneous carriage among hospitalized patients. Cost-effectiveness studies are warranted to evaluate the impact of this assay on infection control procedures in healthcare settings. PMID- 17287321 TI - Milk of cow (Bos taurus), buffalo (Bubalus bubalis), and goat (Capra hircus): a better alternative than fetal bovine serum in media for primary isolation, in vitro cultivation, and maintenance of Leishmania donovani promastigotes. AB - Tyndalized milk of goat, cow, and buffalo was found to be a potential substitute for fetal bovine serum (FBS) in the medium for the cultivation of Leishmania donovani promastigotes. The numbers (means) of promastigotes reached 2.6 x 10(7), 2.3 x 10(7), and 2.1 x 10(7)/ml, respectively, in the medium supplemented with 10% milk of goat, cow, and buffalo, in comparison to 1.9 x 10(7)/ml in the control with 10% FBS. In primary isolation, the milk-supplemented medium showed that 22 out of 26 samples were positive for promastigotes (84.6%) and the cells were maintained successfully during the observed period of 6 months. PMID- 17287322 TI - Characterization of class I Newcastle disease virus isolates from Hong Kong live bird markets and detection using real-time reverse transcription-PCR. AB - Newcastle disease viruses isolated from Hong Kong live bird markets (LBMs) were not detected by a USDA-validated matrix gene real-time reverse transcription-PCR (RT-PCR) assay. Based upon phylogenetic analysis of the fusion gene, these viruses were related to lentogenic class I viruses found in U.S. LBMs and wild waterfowl. An alternative real-time RT-PCR assay which complements the matrix gene assay was developed to efficiently detect class I viruses. PMID- 17287323 TI - Molecular identification of Cryptococcus neoformans serotypes. AB - Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections primarily in immunocompromised hosts. Based on the genetic characteristics and serologic properties of capsular polysaccharides, three varieties and five serotypes have been defined: C. neoformans var. neoformans (serotype D), C. neoformans var. grubii (serotype A), hybrid serotype AD, and C. neoformans var. gattii (serotypes B and C). Epidemiologic features, such as geographic distribution and ecologic niche, and clinical characteristics have been shown to be associated with serotypes. At the present time, serotyping is based on agglutination tests with either commercial or "homemade" antisera or on immunofluorescence assays using a monoclonal antibody directed against the capsule polysaccharide. In this paper, we describe two molecular methods (PCR restriction enzyme analysis and length polymorphism analysis) for C. neoformans serotype identification. Both are based on the sequence characteristics of a fragment of the CAP59 gene required for capsule biosynthesis. Testing of 72 C. neoformans strains including representatives of the five serotypes demonstrated the reliability of these methods. PMID- 17287325 TI - Gluconate-containing intravenous solutions: another cause of false-positive galactomannan assay reactivity. PMID- 17287324 TI - Detection of genes encoding internalization-associated proteins in Streptococcus pyogenes isolates from patients with invasive diseases and asymptomatic carriers. AB - A total of 161 Streptococcus pyogenes isolates from patients with invasive infections or from asymptomatic carriers were examined for genes (prtF1, prtF2, and fba) coding for fibronectin-binding proteins to evaluate their involvement in the pathogenesis of different streptococcal manifestations. We found no significant differences in the presence of these three genes between the two groups. Overall, the prtF2 gene was present in similar percentages among strains from both sources (61% versus 63%). Strains carrying the gene fba were slightly more common among those isolated from asymptomatic carriers (72.6% versus 65%). Also, the prtF1 gene was present in a higher, but not significant, percentage among strains from throat swabs than among isolates from invasive infections (75% versus 64.9%). However, this more detailed characterization of the genes encoding fibronectin-binding proteins allowed us to identify a strong association of genes of the erm class, coding for macrolide resistance, with prtF1 and prtF2 rather than with prtF1 alone. Since macrolide resistance was significantly associated with throat swab isolates, it may be hypothesized that proteins coded by prtF1 and prtF2 genes may be synergic in providing support for cell invasion and/or colonizing or persistence efficiency. PMID- 17287326 TI - Zoonotic vaccinia virus infection in Brazil: clinical description and implications for health professionals. AB - Bovine vaccinia virus outbreaks have been occurring in different regions of Brazil. We report here the time course of natural human infection by vaccinia virus and describe important clinical and epidemiological aspects of this zoonotic infection. The diagnosis of vaccinia virus infection was based on clinical, serological, and molecular procedures. PMID- 17287327 TI - A prospective, randomized, double-blind study of vaginal microflora and epithelium in women using a tampon with an apertured film cover compared with those in women using a commercial tampon with a cover of nonwoven fleece. AB - Healthy women with normal menstrual cycles were randomly assigned to use either a test tampon during cycle 1 and a reference tampon during cycle 2 or a reference tampon during cycle 1 and a test tampon during cycle 2. Tampons were identical except for their cover materials: apertured film for the test tampon and nonwoven fleece for the reference tampon. Product use was doubly blinded. Qualitative and quantitative analyses of vaginal cultures were done pre-, mid-, and postmenstrually for a broad panel of microorganisms, colposcopy was performed, and diary reports were collected; 101 of 105 enrolled subjects completed the study. Midmenstrual findings for a variety of organisms differed from pre- and postmenstrual observations whether subjects were using test or reference tampons. No statistically significant differences were noted in prevalence or colony counts at premenstrual versus mid- and postmenstrual visits for most microorganisms. Prevalences of Gardnerella and anaerobic gram-negative rods were significantly different between tampons at the premenstrual visit, when unusually low values were observed for the test and reference tampons, respectively. None of the changes or differences in microflora were considered to be clinically significant. It is noteworthy, however, that declines in the prevalence and abundance of Lactobacillus during the menstrual periods were less pronounced during the use of both test and reference tampons than those reported from previous studies. Colposcopy showed no abnormal findings with either tampon and no changes in vaginal or cervical epithelial integrity. Thus, all evidence from both microbiological and colposcopic evaluations indicates that the apertured film cover of the test tampon is as safe as the nonwoven cover of the reference tampon. PMID- 17287329 TI - Detection of extended-spectrum beta-lactamases among Enterobacteriaceae by use of semiautomated microbiology systems and manual detection procedures. AB - Three commercially available microbiology identification and susceptibility testing systems were compared with regard to their ability to detect extended spectrum beta-lactamase (ESBL) production in Enterobacteriaceae, i.e., the Phoenix Automated Microbiology System (BD Diagnostic Systems, Sparks, MD), the VITEK 2 System (bioMerieux, Marcy l'Etoile, France), and the MicroScan WalkAway 96 System (Dade Behring, Inc., West Sacramento, CA), using routine testing panels. One hundred fifty putative ESBL producers were distributed blindly to three participating laboratories. Conventional phenotypic confirmatory tests such as the disk approximation method, the CLSI double-disk synergy test, and the Etest ESBL were also evaluated. Biochemical and molecular characterization of beta-lactamases performed at an independent laboratory was used as the reference method. One hundred forty-seven isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Serratia marcescens, Proteus mirabilis, Proteus vulgaris, and Morganella morganii were investigated. Of these isolates, 85 were identified as ESBL producers by the reference method. The remaining isolates were identified as non-ESBL producers; they were either hyperproducers of their chromosomal AmpC, Koxy, or SHV enzymes or lacked any detectable beta-lactamase activity. The system with the highest sensitivity for the detection of ESBLs was the Phoenix (99%), followed by the VITEK 2 (86%) and the MicroScan (84%); however, specificity was more variable, ranging from 52% (Phoenix) to 78% (VITEK 2). The performance of the semiautomated systems differed widely with the species investigated. The sensitivities of the conventional test methods ranged from 93 to 94%. The double disk synergy test showed the highest specificity and positive predictive value among all test methods, i.e., 97% and 98%, respectively. PMID- 17287330 TI - Multicenter evaluation of a commercial PCR-enzyme-linked immunosorbent assay diagnostic kit (Onychodiag) for diagnosis of dermatophytic onychomycosis. AB - We prospectively evaluated a new PCR-enzyme-linked immunosorbent assay kit (Onychodiag; BioAdvance, France) for the diagnosis of dermatophytic onychomycosis by testing nail samples from 438 patients with suspected onychomycosis and from 108 healthy controls in three independent laboratories. In two laboratories, samples were collected by trained mycologists as close as possible to the lesions (proximal samples). In one laboratory, samples were collected by other physicians. All samples were processed by conventional mycological techniques and by Onychodiag, blindly to the mycological results. An additional distal sample, collected by clipping the nail plate, was obtained from 75 patients and tested with Onychodiag alone. In patients with culture-proven dermatophytic onychomycosis, the sensitivity of Onychodiag was 83.6% (87.9% including the gray zone) and ranged from 75 to 100% according to the laboratory and the sampling conditions. The specificity was 100% when healthy subjects were considered true negative controls. Onychodiag was positive on 68 patient samples that were sterile or yielded nondermatophyte species in culture. Based on the results of Onychodiag for mycologically proven positive samples and true-negative samples, these results were considered true positives, and the poor performance of mycology on these samples was attributed to inconvenient sampling conditions or to contaminants. When tested on distal samples, Onychodiag was positive in 49/53 (92%) cases of proven dermatophytic onychomycosis. Finally, with either proximal or distal samples, Onychodiag provided a diagnosis of dermatophytic onychomycosis within 24 to 48 h after sampling, and its sensitivity was close to that of mycological techniques applied to proximal samples. PMID- 17287331 TI - Retrospective species identification of microsporidian spores in diarrheic fecal samples from human immunodeficiency virus/AIDS patients by multiplexed fluorescence in situ hybridization. AB - In order to assess the applicability of multiplexed fluorescence in situ hybridization (FISH) assay for the clinical setting, we conducted retrospective analysis of 110 formalin-stored diarrheic stool samples from human immunodeficiency virus (HIV)/AIDS patients with intestinal microsporidiosis collected between 1992 and 2003. The multiplexed FISH assay identified microsporidian spores in 94 of 110 (85.5%) samples: 49 (52.1%) were positive for Enterocytozoon bieneusi, 43 (45.8%) were positive for Encephalitozoon intestinalis, 2 (2.1%) were positive for Encephalitozoon hellem, and 9 samples (9.6%) contained both E. bieneusi and E. intestinalis spores. Quantitative spore counts per ml of stool yielded concentration values from 3.5 x 10(3) to 4.4 x 10(5) for E. bieneusi (mean, 8.8 x 10(4)/ml), 2.3 x 10(2) to 7.8 x 10(4) (mean, 1.5 x 10(4)/ml) for E. intestinalis, and 1.8 x 10(2) to 3.6 x 10(2) for E. hellem (mean, 2.7 x 10(2)/ml). Identification of microsporidian spores by multiplex FISH assay was more sensitive than both Chromotrope-2R and CalcoFluor White M2R stains; 85.5% versus 72.7 and 70.9%, respectively. The study demonstrated that microsporidian coinfection in HIV/AIDS patients with intestinal microsporidiosis is not uncommon and that formalin-stored fecal samples older than 10 years may not be suitable for retrospective analysis by techniques targeting rRNA. Multiplexed FISH assay is a reliable, quantitative fluorescence microscopy method for the simultaneous identification of E. bieneusi, E. intestinalis, and E. hellem, as well as Encephalitozoon cuniculi, spores in fecal samples and is a useful tool for assessing spore shedding intensity in intestinal microsporidiosis. The method can be used for epidemiological investigations and applied in clinical settings. PMID- 17287332 TI - Identification of "Haematobacter," a new genus of aerobic Gram-negative rods isolated from clinical specimens, and reclassification of Rhodobacter massiliensis as "Haematobacter massiliensis comb. nov.". AB - Twelve strains of gram-negative, nonfermenting rods recovered mainly from septicemic patients were studied using conventional and molecular methods. The phenotypic profiles of these strains most closely resembled Psychrobacter phenylpyruvicus. They produced catalase, oxidase, urease, and H(2)S (lead acetate paper) but did not produce indole, reduce nitrate or nitrite, or hydrolyze gelatin or esculin. No acid production was observed in a King's oxidation fermentation base containing d-glucose, d-xylose, d-mannitol, sucrose, lactose, or maltose. All strains were nonmotile and nonpigmented. Most strains produced green discoloration on blood agar. All strains grew at 25 degrees C and 35 degrees C and most grew on MacConkey agar. They shared a common cellular fatty acid (CFA) profile characterized by large amounts (56% to 90%) of 18:1omega7c and the presence of 3-OH-10:0, 16:1omega7c, 16:0, and 19:0cycomega8c that overall was most similar to that of Rhodobacter species but was quite distinct from that of P. phenylpyruvicus. The MICs for most beta-lactams, fluoroquinolones, aminoglycosides, and carbapenems were low. MICs for aztreonam and piperacillin were higher, with MICs for some strains of > 64 mg/liter and > 128 mg/liter, respectively. Polyphasic analysis of these strains, including morphological, biochemical, CFA composition, DNA-DNA hybridization, 16S rRNA gene sequencing, and percent guanine-plus-cytosine (G+C) content analysis, demonstrated that these strains and Rhodobacter massiliensis represent a new genus, "Haematobacter" (proposed name), with the species H. missouriensis (type strain H1892(T) = CCUG 52307(T) = CIP 109176(T)) and H. massiliensis comb. nov. (type strain Framboise(T) = CCUG 47968(T) = CIP 107725(T)) and an unnamed genomospecies. PMID- 17287333 TI - Evaluation of VITEK 2 and RapID yeast plus systems for yeast species identification: experience at a large clinical microbiology laboratory. AB - A total of 750 clinical yeast isolates were evaluated by two identification systems, VITEK 2 and RapID Yeast Plus, using sequence analysis of the rRNA gene internal transcribed spacer regions as the reference method. The VITEK 2 and RapID systems correctly identified 737 (98.2%) and 716 (95.5%) isolates, respectively. PMID- 17287334 TI - Epidemiologic analysis of reactivated cytomegalovirus antigenemia in patients with cancer. AB - The epidemiologic features of reactivated cytomegalovirus (CMV) antigenemia were studied among 4,382 cancer patients who were cared for and tested at the University of Texas M. D. Anderson Cancer Center from 2001 to 2004. The effects of stem cell transplant (SCT) status, underlying disease, age, sex, ethnicity, and antibody status (prior to CMV exposure) on the incidence of CMV antigenemia were determined; and the CMV burdens were quantified. Antigenemia occurred in 9.3% of patients with non-SCT (n = 2511), 12.0% with autologous SCT (n = 582), and 39.1% with allogeneic SCT (n = 1289). Non-SCT patients with lymphoid tumors had a significantly higher rate of antigenemia than those with myeloid tumors (13.6% versus 3.9%) (P < 0.001); however, after allogeneic SCT, the underlying diseases had little effect, except for multiple myeloma (56.8%) (P = 0.014). Among the allogeneic SCT recipients, higher CMV antigenemia rates were also associated with female sex, older age, and positivity for pre-SCT CMV antibody. Depending on the underlying disease and its associated initial CMV risk, allogeneic SCT increased the risk by 2.6- to 29.6-fold (overall, 4.0-fold). With or without SCT, Asians had the highest CMV antigenemia rates and burdens, followed by blacks, Hispanics, and whites, and these partially correlated with antibody prevalence. Among the 808 patients with antigenemia, the circulating peak CMV burden was significantly higher among non-SCT patients (geometric mean, 18.7 positive cells per 10(6) leukocytes) than among allogeneic SCT patients (geometric mean, 7.7 positive cells per 10(6) leukocytes) or autologous SCT patients (geometric mean, 7.0 positive cells per 10(6) leukocytes) who underwent monitoring for CMV. Together, these results allow stratification of CMV risks and suggest a substantial CMV reactivation among non-SCT cancer patients and, thus, the need for better diagnosis and control. PMID- 17287328 TI - Use of sequence analysis of the NS5B region for routine genotyping of hepatitis C virus with reference to C/E1 and 5' untranslated region sequences. AB - Nucleotide sequence analysis of the NS5B region was performed to identify genotypes of 8,479 hepatitis C virus (HCV) RNA-positive patient samples collected in the Canadian province of Quebec. Genotypes could be determined for 97.3% of patients. Genotypes 1 to 6 were found in 59.4, 9.0, 25.7, 3.6, 0.6, and 1.8% of patients, respectively. Two isolates did not classify within the six genotypes. The subtype 1 distribution was 76.7% 1a, 22.6% 1b, and 0.7% others, while the subtype 2 distribution was 31.8% 2a, 47.6% 2b, 10.9% 2c, 4.1% 2i, and 5.6% others. Subtype 3a accounted for 99.1% of genotype 3 strains, while all genotype 5 samples were of subtype 5a. The subtype 4 distribution was 39.2% 4a, 15.4% 4k, 11.6% 4d, 10.2% 4r, and 23.6% others. The subtype 6 distribution was 40.4% 6e, 20.5% 6a, and 39.1% others. The 5' untranslated region (5'UTR) sequences of subtype 6e were indistinguishable from those of genotype 1. All samples that did not classify within the established subtypes were also sequenced in C/E1 and 5'UTR. C/E1 phylogenetic reconstructions were analogous to those of NS5B. The sequences identified in this study allowed the provisional assignments of subtypes 1j, 1k, 2m, 2r, 3i, 4q, 6q, 6r, and 6s. Sixty-four (0.8%) isolates classifying within genotypes 1 to 6 could not be assigned to one of the recognized subtypes. Our results show that genotyping of HCV by nucleotide sequence analysis of NS5B is efficient, allows the accurate discrimination of subtypes, and is an effective tool for studying the molecular epidemiology of HCV. PMID- 17287335 TI - High frequencies of clindamycin and tetracycline resistance in methicillin resistant Staphylococcus aureus pulsed-field type USA300 isolates collected at a Boston ambulatory health center. AB - Individual or multiple resistance to clindamycin, tetracycline, erythromycin, levofloxacin, or mupirocin was detected in a large proportion of methicillin resistant Staphylococcus aureus pulsed-field type USA300 isolates collected at an ambulatory health center in Boston. The clindamycin, tetracycline, and mupirocin resistance genes identified in these isolates are commonly associated with plasmids. PMID- 17287336 TI - Deletion of fetA gene sequences in serogroup B and C Neisseria meningitidis isolates. AB - The immunogenic iron-regulated FetA outer membrane protein of Neisseria meningitidis is one of various outer membrane proteins that have been considered potential meningococcal vaccine candidates. In this report, we describe the characterization of three meningococcal isolates that have deleted fetA sequences through genetic recombination at repetitive elements. PMID- 17287337 TI - Therapeutic anticancer efficacy of a synthetic diazonamide analog in the absence of overt toxicity. AB - Blocking cell division through the inhibition of mitosis is one of the most successful clinical strategies for the treatment of cancer. Taxanes and vinca alkaloids are in widespread use and have demonstrated substantive therapeutic efficacy. Both classes of compounds bind directly to tubulin, a structural component of the mitotic spindle. The ubiquitous utilization of tubulin in cell division in both cancerous and normal cells, however, tempers the broad spectrum of activity of currently used antimitotics by significant toxicities in normal dividing tissue. Moreover, peripheral nerve cells that rely on microtubules to shuttle cargo along axonal processes are also damaged by tubulin-binding drugs. Thus, neutropenia and peripheral neuropathy are the most frequently cited dose limiting toxicities of this class of chemotherapeutics. Here we report the preclinical assessment of AB-5, a structural and functional analog of the natural product diazonamide A. AB-5, like taxanes and vinca alkaloids, blocks cell division during mitosis. However, AB-5 works not by binding tubulin but rather through inhibition of a newly discovered role for ornithine-delta aminotransferase in mitosis. We hereby report that, unlike other antimitotics, AB 5 is extremely well tolerated by mice when administered under conditions where the drug cures xenografted tumors as effectively as taxanes and vinca alkaloids. AB-5-treated mice show no weight loss, no change in overall physical appearance, and no evidence of neutropenia. These observations raise the possibility that AB 5 may have clinical utility for cancer therapy under conditions largely devoid of chemotherapeutic toxicity and suggest that further preclinical evaluation of AB-5 is warranted. PMID- 17287338 TI - 1-Methyl-4-phenylpyridinium affects fast axonal transport by activation of caspase and protein kinase C. AB - Parkinson's disease (PD), a late-onset condition characterized by dysfunction and loss of dopaminergic neurons in the substantia nigra, has both sporadic and neurotoxic forms. Neurotoxins such as 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine and its metabolite 1-methyl-4-phenylpyridinium (MPP+) induce PD symptoms and recapitulate major pathological hallmarks of PD in human and animal models. Both sporadic and MPP+-induced forms of PD proceed through a "dying-back" pattern of neuronal degeneration in affected neurons, characterized by early loss of synaptic terminals and axonopathy. However, axonal and synaptic specific effects of MPP+ are poorly understood. Using isolated squid axoplasm, we show that MPP+ produces significant alterations in fast axonal transport (FAT) through activation of a caspase and a previously undescribed protein kinase C (PKCdelta) isoform. Specifically, MPP+ increased cytoplasmic dynein-dependent retrograde FAT and reduced kinesin-1-mediated anterograde FAT. Significantly, MPP+ effects were independent of both nuclear activities and ATP production. Consistent with its effects on FAT, MPP+ injection in presynaptic domains led to a dramatic reduction in the number of membranous profiles. Changes in availability of synaptic and neurotrophin-signaling components represent axonal and synaptic-specific effects of MPP+ that would produce a dying-back pathology. Our results identify a critical neuronal process affected by MPP+ and suggest that alterations in vesicle trafficking represent a primary event in PD pathogenesis. We propose that PD and other neurodegenerative diseases exhibiting dying-back neuropathology represent a previously undescribed category of neurological diseases characterized by dysfunction of vesicle transport and associated with the loss of synaptic function. PMID- 17287339 TI - 1-Methyl-4-phenylpyridinium induces synaptic dysfunction through a pathway involving caspase and PKCdelta enzymatic activities. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration has been used, in various mammalian species, as an experimental model of Parkinson's disease. The pathogenesis for such pharmacologically induced Parkinson's disease involves 1 methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine. This metabolite produces rapid degeneration of nigrostriatal dopaminergic neurons, which causes the parkinsonian syndrome. In this work, we show that injection of MPP+ into the presynaptic terminal of the squid giant synapse blocks synaptic transmission without affecting the presynaptic action potential or the presynaptic calcium currents. These effects of MPP+ were mimicked by the injection of an active form of caspase-3 and prevented by inhibitors of caspase-3 and protein kinase C delta. Ultrastructurally, MPP+-injected synapses showed a dramatic reduction in the number of neurotransmitter vesicles at the presynaptic active zone, as compared with control synapses. Otherwise, normal docking and clathrin-coated vesicles were observed, albeit at much reduced numbers. These results indicate that MPP+ acutely reduces presynaptic vesicular availability, not release, and that MPP+ induced pathogenesis results from presynaptic dysfunction that leads, secondarily, to dying-back neuropathy in affected neurons. PMID- 17287340 TI - Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. AB - Electron transfer dissociation (ETD) is a recently introduced mass spectrometric technique that provides a more comprehensive coverage of peptide sequences and posttranslational modifications. Here, we evaluated the use of ETD for a global phosphoproteome analysis. In all, we identified a total of 1,435 phosphorylation sites from human embryonic kidney 293T cells, of which 1,141 ( approximately 80%) were not previously described. A detailed comparison of ETD and collision-induced dissociation (CID) modes showed that ETD identified 60% more phosphopeptides than CID, with an average of 40% more fragment ions that facilitated localization of phosphorylation sites. Although our data indicate that ETD is superior to CID for phosphorylation analysis, the two methods can be effectively combined in alternating ETD and CID modes for a more comprehensive analysis. Combining ETD and CID, from this single study, we were able to identify 80% of the known phosphorylation sites in >1,000 phosphorylated peptides analyzed. A hierarchical clustering of the identified phosphorylation sites allowed us to discover 15 phosphorylation motifs that have not been reported previously. Overall, ETD is an excellent method for localization of phosphorylation sites and should be an integral component of any strategy for comprehensive phosphorylation analysis. PMID- 17287341 TI - Uniformity amid diversity in RNase P. PMID- 17287342 TI - Assessment of nitric oxide signals by triiodide chemiluminescence. AB - Nitric oxide (NO) bioactivity is mainly conveyed through reactions with iron and thiols, furnishing iron nitrosyls and S-nitrosothiols with wide-ranging stabilities and reactivities. Triiodide chemiluminescence methodology has been popularized as uniquely capable of quantifying these species together with NO byproducts, such as nitrite and nitrosamines. Studies with triiodide, however, have challenged basic ideas of NO biochemistry. The assay, which involves addition of multiple reagents whose chemistry is not fully understood, thus requires extensive validation: Few protein standards have in fact been characterized; NO mass balance in biological mixtures has not been verified; and recovery of species that span the range of NO-group reactivities has not been assessed. Here we report on the performance of the triiodide assay vs. photolysis chemiluminescence in side-by-side assays of multiple nitrosylated standards of varied reactivities and in assays of endogenous Fe- and S-nitrosylated hemoglobin. Although the photolysis method consistently gives quantitative recoveries, the yields by triiodide are variable and generally low (approaching zero with some standards and endogenous samples). Moreover, in triiodide, added chemical reagents, changes in sample pH, and altered ionic composition result in decreased recoveries and misidentification of NO species. We further show that triiodide, rather than directly and exclusively producing NO, also produces the highly potent nitrosating agent, nitrosyliodide. Overall, we find that the triiodide assay is strongly influenced by sample composition and reactivity and does not reliably identify, quantify, or differentiate NO species in complex biological mixtures. PMID- 17287343 TI - Spinal cholinergic interneurons regulate the excitability of motoneurons during locomotion. AB - To effect movement, motoneurons must respond appropriately to motor commands. Their responsiveness to these inputs, or excitability, is regulated by neuromodulators. Possible sources of modulation include the abundant cholinergic "C boutons" that surround motoneuron somata. In the present study, recordings from motoneurons in spinal cord slices demonstrated that cholinergic activation of m2-type muscarinic receptors increases excitability by reducing the action potential afterhyperpolarization. Analyses of isolated spinal cord preparations in which fictive locomotion was elicited demonstrated that endogenous cholinergic inputs increase motoneuron excitability during locomotion. Anatomical data indicate that C boutons originate from a discrete group of interneurons lateral to the central canal, the medial partition neurons. These results highlight a unique component of spinal motor networks that is critical in ensuring that sufficient output is generated by motoneurons to drive motor behavior. PMID- 17287344 TI - Kinetic models of redox-coupled proton pumping. AB - Cytochrome c oxidase, the terminal enzyme of the respiratory chain, pumps protons across the inner mitochondrial membrane against an opposing electrochemical gradient by reducing oxygen to water. To explore the fundamental mechanisms of such redox-coupled proton pumps, we develop kinetic models at the single-molecule level consistent with basic physical principles. We demonstrate that pumping against potentials >150 mV can be achieved purely through electrostatic couplings, given an asymmetric arrangement of charge centers; however, nonlinear gates are essential for highly efficient real enzymes. The fundamental requirements for proton pumping identified here highlight a possible evolutionary origin of cytochrome c oxidase pumping. The general design principles are relevant also for other molecular machines and suggest future applications in biology-inspired fuel cells. PMID- 17287345 TI - Amelioration of progressive renal injury by genetic manipulation of Klotho gene. AB - Klotho, an antiaging gene with restricted organ distribution, is mainly expressed in the kidney tubules; the mutant mice have shortened life span, arteriosclerosis, anemia, and osteoporesis, features common to patients with chronic renal failure. Conceivably, the reduction of the Klotho gene expression may contribute to the development of kidney failure; alternatively, its overexpression may lead to the amelioration of renal injury in an ICR-derived glomerulonephritis (ICGN) mouse model with subtle immune complex-mediated disease. To address this issue, four different strains of mice were generated by cross-breeding: ICGN mice without the Klotho transgene (ICGN), ICGN mice with the Klotho transgene (ICGN/klTG), wild-type mice with the Klotho transgene (klTG), and wild-type mice without the Klotho transgene (control). At 40 weeks old, the survival rate was approximately 30% in ICGN mice, and approximately 70% in the ICGN/klTG group. This improvement was associated with dramatic improvement in renal functions, morphological lesions, and cytochrome c oxidase activity but a reduction in beta-galactosidase activity (a senescence-associated protein), mitochondrial DNA fragmentation, superoxide anion generation, lipid peroxidation, and Bax protein expression and apoptosis. Interestingly, improvement was seen in both the tubular and glomerular compartments of the kidney, although Klotho is exclusively confined to the tubules, suggesting that its gene product has a remarkable renoprotective effect by potentially serving as a circulating hormone while mitigating the mitochondrial oxidative stress. PMID- 17287346 TI - Deletion of CASK in mice is lethal and impairs synaptic function. AB - CASK is an evolutionarily conserved multidomain protein composed of an N-terminal Ca2+/calmodulin-kinase domain, central PDZ and SH3 domains, and a C-terminal guanylate kinase domain. Many potential activities for CASK have been suggested, including functions in scaffolding the synapse, in organizing ion channels, and in regulating neuronal gene transcription. To better define the physiological importance of CASK, we have now analyzed CASK "knockdown" mice in which CASK expression was suppressed by approximately 70%, and CASK knockout (KO) mice, in which CASK expression was abolished. CASK knockdown mice are viable but smaller than WT mice, whereas CASK KO mice die at first day after birth. CASK KO mice exhibit no major developmental abnormalities apart from a partially penetrant cleft palate syndrome. In CASK-deficient neurons, the levels of the CASK interacting proteins Mints, Veli/Mals, and neurexins are decreased, whereas the level of neuroligin 1 (which binds to neurexins that in turn bind to CASK) is increased. Neurons lacking CASK display overall normal electrical properties and form ultrastructurally normal synapses. However, glutamatergic spontaneous synaptic release events are increased, and GABAergic synaptic release events are decreased in CASK-deficient neurons. In contrast to spontaneous neurotransmitter release, evoked release exhibited no major changes. Our data suggest that CASK, the only member of the membrane-associated guanylate kinase protein family that contains a Ca2+/calmodulin-dependent kinase domain, is required for mouse survival and performs a selectively essential function without being in itself required for core activities of neurons, such as membrane excitability, Ca2+ triggered presynaptic release, or postsynaptic receptor functions. PMID- 17287347 TI - Internal strain regulates the nucleotide binding site of the kinesin leading head. AB - In the presence of ATP, kinesin proceeds along the protofilament of microtubule by alternated binding of two motor domains on the tubulin binding sites. Because the processivity of kinesin is much higher than other motor proteins, it has been speculated that there exists a mechanism for allosteric regulation between the two monomers. Recent experiments suggest that ATP binding to the leading head (L) domain in kinesin is regulated by the rearward strain built on the neck-linker. We test this hypothesis by explicitly modeling a Calpha-based kinesin structure whose motor domains are bound on the tubulin binding sites. The equilibrium structures of kinesin on the microtubule show disordered and ordered neck-linker configurations for the L and trailing head, respectively. The comparison of the structures between the two heads shows that several native contacts present at the nucleotide binding site in the L are less intact than those in the binding site of the rear head. The network of native contacts obtained from this comparison provides the internal tension propagation pathway, which leads to the disruption of the nucleotide binding site in the L. Also, using an argument based on polymer theory, we estimate the internal tension built on the neck-linker to be f approximately 12-15 pN. Both of these conclusions support the experimental hypothesis. PMID- 17287348 TI - Absence of metabotropic glutamate receptor-mediated plasticity in the neocortex of fragile X mice. AB - Fragile X syndrome is a common heritable form of mental retardation in humans. Recent neuroanatomical studies indicate an apparent immature appearance of neurons in fragile X syndrome patients and fragile X mental retardation protein (FMRP)-knockout mice, an animal model of this condition. In this work, we investigated possible alterations in synaptic plasticity in the neocortex of FMRP knockout mice. Extracellular field potentials were recorded from the deep-layer visual neocortex. Long-term potentiation (LTP) was severely attenuated in brain slices from knockout mice relative to that observed in slices from wild-type mice. Considering that neocortical LTP can involve both NMDA receptor-dependent and -independent mechanisms, we attempted to distinguish the nature of LTP attenuated in the knockout condition. In slices from wild-type mice, LTP was partially attenuated by the NMDA receptor antagonist 3-[(+/-)-2-carboxypiperazin 4-yl]-propyl-1-phosphate (CPP); however, the general metabotropic glutamate receptor (mGluR) antagonist alpha-methyl-4-carboxyphenylglycine (MCPG) strongly attenuated LTP, resulting in a response indistinguishable from that observed in slices from knockout mice. The selective mGluR5 antagonist 2-methyl-6 (phenylethynyl)-pyridine (MPEP) attenuated LTP to a similar degree as did MCPG in wild-type slices, but MPEP did not alter the reduced potentiation in knockout slices. Our results suggest that LTP in layer V visual neocortex depends primarily on mGluR5 activation. Our data also indicate that mGluR5-mediated synaptic plasticity is absent in the neocortex of FMRP-knockout mice. Such an alteration may contribute to the cognitive and learning deficits exhibited in these mice as well as in fragile X syndrome. PMID- 17287349 TI - O-specific [corrected] polysaccharide conjugate vaccine-induced [corrected] antibodies prevent invasion of Shigella into Caco-2 cells and may be curative. AB - The O-specific polysaccharide (O-SP) domain of Shigella LPS is both an essential virulence factor and a protective antigen for this genus. A critical level of serum IgG anti-O-SP was shown to confer immunity to shigellosis, likely by complement-mediated bacteriolysis of the inoculum. Conjugate Shigella O-SP vaccines were shown to be safe and immunogenic in children, and, in a preliminary study, Shigella sonnei vaccine was protective in young adults. Characteristic of shigellosis is bacterial invasion of intestinal cells. Incubation of shigellae with postimmunization but not preimmunization sera of children vaccinated with S. sonnei or Shigella flexneri 2a O-SP conjugate vaccines inhibited in a type specific and dose-dependent manner in vitro invasion of intestinal epithelial cells (Caco-2) and the infection-associated increases in IL-1beta and IL-8 mRNA and extracellular cytokine levels. Pretreatment of these sera or of Caco-2 cells with O-SP abrogated these effects also in a type-specific and dose-dependent manner. Confocal microscopy demonstrated antibody-specific inhibition of bacterial adhesion to HeLa cells. These protective effects were duplicated by IgG purified from these sera. These results suggest a dual role for IgG anti-O-SP. In addition to lysis of the inoculum in immune individuals, the newly synthesized IgG anti-O-SP in patients may terminate an established infection by inhibiting shigellae released from epithelial cells from invading new ones. A critical level of IgG anti-O-SP could, therefore, have a protective as well as a curative role in shigellosis. PMID- 17287350 TI - Diazonamide toxins reveal an unexpected function for ornithine delta-amino transferase in mitotic cell division. AB - We have studied a naturally occurring small-molecule antimitotic called diazonamide A. Diazonamide A is highly effective at blocking spindle assembly in mammalian cell culture and does so through a unique mechanism. A biotinylated form of diazonamide A affinity purifies ornithine delta-amino transferase (OAT), a mitochondrial enzyme, from HeLa cell and Xenopus egg extracts. In the latter system, the interaction between diazonamide A and OAT is regulated by RanGTP. We find that specific OAT knockdown in human cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death, the effects largely phenocopying diazonamide A treatment in these cell lines. Our experiments reveal an unanticipated, paradoxical role for OAT in mitotic cell division and identify the protein as a target for chemotherapeutic drug development. PMID- 17287351 TI - The PsbQ protein defines cyanobacterial Photosystem II complexes with highest activity and stability. AB - Light-induced conversion of water to molecular oxygen by Photosystem II (PSII) is one of the most important enzymatic reactions in the biosphere. PSII is a multisubunit membrane protein complex with numerous associated cofactors, but it continually undergoes assembly and disassembly due to frequent light-mediated damage as a result of its normal function. Thus, at any instant, there is heterogeneity in the subunit compositions of PSII complexes within the cell. In particular, cyanobacterial PSII complexes have five associated extrinsic proteins, PsbO, PsbP, PsbQ, PsbU, and PsbV. However, little is known about the interactions of the more recently identified PsbQ protein with other components in cyanobacterial PSII. Here we show that PSII complexes can be isolated from the cyanobacterium Synechocystis sp. PCC 6803 on the basis of the presence of a polyhistidine-tagged PsbQ protein. Purification of PSII complexes using a tagged extrinsic protein has not been previously described, and this work conclusively demonstrates that PsbQ is present in combination with the PsbO, PsbU, and PsbV proteins in cyanobacterial PSII. Moreover, PsbQ-associated PSII complexes have higher activity and stability relative to those isolated using histidine-tagged CP47, an integral membrane protein. Therefore, we conclude that the presence of PsbQ defines the fully assembled and optimally active form of the enzyme. PMID- 17287352 TI - Dynamic oligomeric conversions of the cytoplasmic RCK domains mediate MthK potassium channel activity. AB - The crystal structure of the RCK-containing MthK provides a molecular framework for understanding the ligand gating mechanisms of K+ channels. Here we examined the macroscopic currents of MthK in enlarged Escherichia coli membrane by patch clamp and rapid perfusion techniques and showed that the channel undergoes desensitization in seconds after activation by Ca2+ or Cd2+. Additionally, MthK is inactivated by slightly acidic pH only from the cytoplasmic side. Examinations of isolated RCK domain by size-exclusion chromatography, static light scattering, analytical sedimentation, and stopped-flow spectroscopy show that Ca2+ rapidly converts isolated RCK monomers to multimers at alkaline pH. In contrast, the RCK domain at acidic pH remains firmly dimeric regardless of Ca2+ but restores predominantly to multimer or monomer at basic pH with or without Ca2+, respectively. These functional and biochemical analyses correlate the four functional states of the MthK channel with distinct oligomeric states of its RCK domains and indicate that the RCK domains undergo oligomeric conversions in modulating MthK activities. PMID- 17287353 TI - Substrate product equilibrium on a reversible enzyme, triosephosphate isomerase. AB - The highly efficient glycolytic enzyme, triosephosphate isomerase, is expected to differentially stabilize the proposed stable reaction species: ketone, aldehyde, and enediol(ate). The identity and steady-state populations of the chemical entities bound to triosephosphate isomerase have been probed by using solid- and solution-state NMR. The 13C-enriched ketone substrate, dihydroxyacetone phosphate, was bound to the enzyme and characterized at steady state over a range of sample conditions. The ketone substrate was observed to be the major species over a temperature range from -60 degrees C to 15 degrees C. Thus, there is no suggestion that the enzyme preferentially stabilizes the reactive intermediate or the product. The predominance of dihydroxyacetone phosphate on the enzyme would support a mechanism in which the initial proton abstraction in the reaction from dihydroxyacetone phosphate to D-glyceraldehyde 3-phosphate is significantly slower than the subsequent chemical steps. PMID- 17287354 TI - Queen pheromone modulates brain dopamine function in worker honey bees. AB - Honey bee queens produce a sophisticated array of chemical signals (pheromones) that influence both the behavior and physiology of their nest mates. Most striking are the effects of queen mandibular pheromone (QMP), a chemical blend that induces young workers to feed and groom the queen and primes bees to perform colony-related tasks. But how does this pheromone operate at the cellular level? This study reveals that QMP has profound effects on dopamine pathways in the brain, pathways that play a central role in behavioral regulation and motor control. In young worker bees, dopamine levels, levels of dopamine receptor gene expression, and cellular responses to this amine are all affected by QMP. We identify homovanillyl alcohol as a key contributor to these effects and provide evidence linking QMP-induced changes in the brain to changes at a behavioral level. This study offers exciting insights into the mechanisms through which QMP operates and a deeper understanding of the queen's ability to regulate the behavior of her offspring. PMID- 17287355 TI - Structure of the cooperative Xis-DNA complex reveals a micronucleoprotein filament that regulates phage lambda intasome assembly. AB - The DNA architectural protein Xis regulates the construction of higher-order nucleoprotein intasomes that integrate and excise the genome of phage lambda from the Escherichia coli chromosome. Xis modulates the directionality of site specific recombination by stimulating phage excision 10(6)-fold, while simultaneously inhibiting phage reintegration. Control is exerted by cooperatively assembling onto a approximately 35-bp DNA regulatory element, which it distorts to preferentially stabilize an excisive intasome. Here, we report the 2.6-A crystal structure of the complex between three cooperatively bound Xis proteins and a 33-bp DNA containing the regulatory element. Xis binds DNA in a head-to-tail orientation to generate a micronucleoprotein filament. Although each protomer is anchored to the duplex by a similar set of nonbase specific contacts, malleable protein-DNA interactions enable binding to sites that differ in nucleotide sequence. Proteins at the ends of the duplex sequence specifically recognize similar binding sites and participate in cooperative binding via protein-protein interactions with a bridging Xis protomer that is bound in a less specific manner. Formation of this polymer introduces approximately 72 degrees of curvature into the DNA with slight positive writhe, which functions to connect disparate segments of DNA bridged by integrase within the excisive intasome. PMID- 17287356 TI - Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae. AB - Respiratory metabolism plays an important role in energy production in the form of ATP in all aerobically growing cells. However, a limitation in respiratory capacity results in overflow metabolism, leading to the formation of byproducts, a phenomenon known as "overflow metabolism" or "the Crabtree effect." The yeast Saccharomyces cerevisiae has served as an important model organism for studying the Crabtree effect. When subjected to increasing glycolytic fluxes under aerobic conditions, there is a threshold value of the glucose uptake rate at which the metabolism shifts from purely respiratory to mixed respiratory and fermentative. It is well known that glucose repression of respiratory pathways occurs at high glycolytic fluxes, resulting in a decrease in respiratory capacity. Despite many years of detailed studies on this subject, it is not known whether the onset of the Crabtree effect is due to limited respiratory capacity or is caused by glucose-mediated repression of respiration. When respiration in S. cerevisiae was increased by introducing a heterologous alternative oxidase, we observed reduced aerobic ethanol formation. In contrast, increasing nonrespiratory NADH oxidation by overexpression of a water-forming NADH oxidase reduced aerobic glycerol formation. The metabolic response to elevated alternative oxidase occurred predominantly in the mitochondria, whereas NADH oxidase affected genes that catalyze cytosolic reactions. Moreover, NADH oxidase restored the deficiency of cytosolic NADH dehydrogenases in S. cerevisiae. These results indicate that NADH oxidase localizes in the cytosol, whereas alternative oxidase is directed to the mitochondria. PMID- 17287357 TI - Adaptations to fluctuating selection in Drosophila. AB - Time-dependent selection causes the adaptive evolution of new phenotypes, and this dynamics can be traced in genomic data. We have analyzed polymorphisms and substitutions in Drosophila, using a more sensitive inference method for adaptations than the standard population-genetic tests. We find evidence that selection itself is strongly time-dependent, with changes occurring at nearly the rate of neutral evolution. At the same time, higher than previously estimated levels of selection make adaptive responses by a factor 10-100 faster than the pace of selection changes, ensuring that adaptations are an efficient mode of evolution under time-dependent selection. The rate of selection changes is faster in noncoding DNA, i.e., the inference of functional elements can less be based on sequence conservation than for proteins. Our results suggest that selection acts not only as a constraint but as a major driving force of genomic change. PMID- 17287358 TI - Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry. AB - We present a strategy for the analysis of the yeast phosphoproteome that uses endo-Lys C as the proteolytic enzyme, immobilized metal affinity chromatography for phosphopeptide enrichment, a 90-min nanoflow-HPLC/electrospray-ionization MS/MS experiment for phosphopeptide fractionation and detection, gas phase ion/ion chemistry, electron transfer dissociation for peptide fragmentation, and the Open Mass Spectrometry Search Algorithm for phosphoprotein identification and assignment of phosphorylation sites. From a 30-microg (approximately 600 pmol) sample of total yeast protein, we identify 1,252 phosphorylation sites on 629 proteins. Identified phosphoproteins have expression levels that range from <50 to 1,200,000 copies per cell and are encoded by genes involved in a wide variety of cellular processes. We identify a consensus site that likely represents a motif for one or more uncharacterized kinases and show that yeast kinases, themselves, contain a disproportionately large number of phosphorylation sites. Detection of a pHis containing peptide from the yeast protein, Cdc10, suggests an unexpected role for histidine phosphorylation in septin biology. From diverse functional genomics data, we show that phosphoproteins have a higher number of interactions than an average protein and interact with each other more than with a random protein. They are also likely to be conserved across large evolutionary distances. PMID- 17287359 TI - Lifelong accumulation of bone in mice lacking Pten in osteoblasts. AB - Bone formation is carried out by the osteoblast, a mesenchymal cell whose lifespan and activity are regulated by growth factor signaling networks. Growth factors activate phosphatidylinositol 3-kinase (PI3K), which enhances cell survival and antagonizes apoptosis through activation of Akt/PKB. This process is negatively regulated by the Pten phosphatase, which inhibits the activity of PI3K. In this study, we investigated the effects of Akt activation in bone in vivo by conditionally disrupting the Pten gene in osteoblasts by using Cre mediated recombination. Mice deficient in Pten in osteoblasts were of normal size but demonstrated a dramatic and progressively increasing bone mineral density throughout life. In vitro osteoblasts lacking Pten differentiated more rapidly than controls and exhibited greatly reduced apoptosis in association with markedly increased levels of phosphorylated Akt and activation of signaling pathways downstream of activated Akt. These findings support a critical role for this tumor-suppressor gene in regulating osteoblast lifespan and likely explain the skeletal abnormalities in patients carrying germ-line mutations of PTEN. PMID- 17287360 TI - Retrolinkin, a membrane protein, plays an important role in retrograde axonal transport. AB - Retrograde axonal transport plays an important role in the maintenance of neuronal functions, but the mechanism is poorly defined partly because the constituents of the retrograde transport system and their interactions have yet to be elucidated. Of special interest is how dynein/dynactin motor proteins interact with membrane cargoes. Here, we report that an endosomal vesicle protein, termed retrolinkin, functions as a receptor tethering vesicles to dynein/dynactin through BPAG1n4. Retrolinkin, a membrane protein highly enriched in neuronal endosomes, binds directly to BPAG1n4. Deletion of retrolinkin membrane-association domains disrupts retrograde vesicular transport, recapitulating the BPAG1 null phenotype. We propose that retrolinkin acts with BPAG1n4 to specifically regulate retrograde axonal transport. Our work lays the foundation for understanding fundamental issues of axonal transport and provides insights into the molecular mechanisms underlying human neurodegenerative disorders. PMID- 17287361 TI - Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI). AB - Dynamic manganese-enhanced magnetic resonance imaging (MEMRI) detects neuronal activity based on the passage of Mn(2+) into active neurons. Because this mechanism is independent of any hemodynamic response, it is potentially ideal for pharmacological studies and was applied to investigate the acute CNS effects of cocaine in the rat. Dose-dependent, region-specific MEMRI signals were seen mostly in cortical and subcortical mesocorticolimbic structures. To verify the spatial accuracy and physiological mechanisms of MEMRI, neuronal activation following electrical forepaw stimulation revealed somatotopic signal enhancement in the primary and secondary somatosensory cortices, which was blocked by diltiazem, a Ca2+ channel antagonist. These data suggest that MEMRI may serve as a tool for investigating the effects of pharmacological agents and opens an application of MRI to study CNS drug effects at a systems level. PMID- 17287363 TI - Intracellular distribution of the lysyl oxidase propeptide in osteoblastic cells. AB - Lysyl oxidase plays a critical role in the formation of the extracellular matrix, and its activity is required for the normal maturation and cross-linking of collagen and elastin. An 18-kDa lysyl oxidase propeptide (LOPP) is generated from 50-kDa prolysyl oxidase by extracellular proteolytic cleavage during the biosynthesis of active 30-kDa lysyl oxidase enzyme. The fate and the functions of the LOPP are largely unknown, although intact LOPP was previously observed in osteoblast cultures. We investigated the spatial localization of molecular forms of lysyl oxidase, including LOPP in proliferating and differentiating osteoblasts, by using confocal immunofluorescence microscopy and Western blots of cytoplasmic and nuclear extracts. In the present study, a stage-dependent intracellular distribution of LOPP in the osteoblastic cell was observed. In proliferating osteoblasts, LOPP epitopes were principally associated with the Golgi and endoplasmic reticulum, and mature lysyl oxidase epitopes were found principally in the nucleus and perinuclear region. In differentiating cells, LOPP and mature lysyl oxidase immunostaining showed clear colocalization with the microtubule network. The subcellular distribution of LOPP and its temporal and physical association with microtubules were confirmed by Western blot and far Western blot studies. We also report that N-glycosylated and nonglycosylated LOPP are present in MC3T3-E1 cell cultures. We conclude that LOPP has a stage dependent intracellular distribution in osteoblastic cells. Future studies are needed to investigate whether the LOPP associations with microtubules or the osteoblast nucleus have functional effects for osteoblast differentiation and bone formation. PMID- 17287364 TI - Cellular trafficking of phospholamban and formation of functional sarcoplasmic reticulum during myocyte differentiation. AB - Phospholamban (PLB) associates with the Ca(2+)-ATPase in sarcoplasmic reticulum (SR) membranes to permit the modulation of contraction in response to beta adrenergic signaling. To understand how coordinated changes in the abundance and intracellular trafficking of PLB and the Ca(2+)-ATPase contribute to the maturation of functional muscle, we measured changes in abundance, location, and turnover of endogenous and tagged proteins in myoblasts and during their differentiation. We found that PLB is constitutively expressed in both myoblasts and differentiated myotubes, whereas abundance increases of the Ca(2+)-ATPase coincide with the formation of differentiated myotubes. We observed that PLB is primarily present in highly mobile vesicular structures outside the endoplasmic reticulum, irrespective of the expression of the Ca(2+)-ATPase, indicating that PLB targeting is regulated through vesicle trafficking. Moreover, using pulse chase methods, we observed that in myoblasts, PLB is trafficked through directed transport through the Golgi to the plasma membrane before endosome-mediated internalization. The observed trafficking of PLB to the plasma membrane suggests an important role for PLB during muscle differentiation, which is distinct from its previously recognized role in the regulation of the Ca(2+)-ATPase. PMID- 17287365 TI - Salutary effects of 17beta-estradiol on T-cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-alpha. AB - Although 17beta-estradiol (E2) administration following trauma-hemorrhage prevents the suppression in splenocyte cytokine production, it remains unknown whether the salutary effects of 17beta-estradiol are mediated via estrogen receptor (ER)-alpha or ER-beta. Moreover, it is unknown which signaling pathways are involved in 17beta-estradiol's salutary effects. Utilizing an ER-alpha- or ER beta-specific agonist, we examined the role of ER-alpha and ER-beta in E2 mediated restoration of T-cell cytokine production following trauma-hemorrhage. Moreover, since MAPK, NF-kappaB, and activator protein (AP)-1 are known to regulate T-cell cytokine production, we also examined the activation of MAPK, NF kappaB, and AP-1. Male rats underwent trauma-hemorrhage (mean arterial pressure 40 mmHg for 90 min) and fluid resuscitation. ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), 17beta-estradiol (50 microg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four hours thereafter, splenic T cells were isolated, and their IL-2 and IFN-gamma production and MAPK, NF-kappaB, and AP-1 activation were measured. T-cell IL-2 and IFN-gamma production was decreased following trauma-hemorrhage, and this was accompanied with a decrease in T-cell MAPK, NF-kappaB, and AP-1 activation. PPT or 17beta-estradiol administration following trauma-hemorrhage normalized those parameters, while DPN administration had no effect. Since PPT, but not DPN, administration following trauma-hemorrhage was as effective as 17beta-estradiol in preventing the T-cell suppression, it appears that ER-alpha plays a predominant role in mediating the salutary effects of 17beta-estradiol on T cells following trauma-hemorrhage, and that such effects are likely mediated via normalization of MAPK, NF-kappaB, and AP-1 signaling pathways. PMID- 17287362 TI - New VMD2 gene mutations identified in patients affected by Best vitelliform macular dystrophy. AB - PURPOSE: The mutations responsible for Best vitelliform macular dystrophy (BVMD) are found in a gene called VMD2. The VMD2 gene encodes a transmembrane protein named bestrophin-1 (hBest1) which is a Ca(2+)-sensitive chloride channel. This study was performed to identify disease-specific mutations in 27 patients with BVMD. Because this disease is characterised by an alteration in Cl(-) channel function, patch clamp analysis was used to test the hypothesis that one of the VMD2 mutated variants causes the disease. METHODS: Direct sequencing analysis of the 11 VMD2 exons was performed to detect new abnormal sequences. The mutant of hBest1 was expressed in HEK-293 cells and the associated Cl(-) current was examined using whole-cell patch clamp analysis. RESULTS: Six new VMD2 mutations were identified, located exclusively in exons four, six and eight. One of these mutations (Q293H) was particularly severe. Patch clamp analysis of human embryonic kidney cells expressing the Q293H mutant showed that this mutant channel is non-functional. Furthermore, the Q293H mutant inhibited the function of wild-type bestrophin-1 channels in a dominant negative manner. CONCLUSIONS: This study provides further support for the idea that mutations in VMD2 are a necessary factor for Best disease. However, because variable expressivity of VMD2 was observed in a family with the Q293H mutation, it is also clear that a disease linked mutation in VMD2 is not sufficient to produce BVMD. The finding that the Q293H mutant does not form functional channels in the membrane could be explained either by disruption of channel conductance or gating mechanisms or by improper trafficking of the protein to the plasma membrane. PMID- 17287366 TI - Phenylephrine hypertrophy, Ca2+-ATPase (SERCA2), and Ca2+ signaling in neonatal rat cardiac myocytes. AB - We endeavored to use a basic and well-controlled experimental system to characterize the extent and time sequence of sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) involvement in the development of cardiac hypertrophy, including transcription, protein expression, Ca(2+) transport, and cytoplasmic Ca(2+) signaling. To this end, hypertrophy of neonatal rat cardiac myocytes in culture was obtained after adrenergic activation with phenylephrine (PE). Micrographic assessment of myocyte size, rise of [(14)C]phenylalanine incorporation and total protein expression, and increased transcription of atrial natriuretic factor demonstrated unambiguously the occurrence of hypertrophy. An early and prominent feature of hypertrophy was a reduction of the SERCA2 transcript, as determined by RT-PCR with reference to a stable marker such as glyceraldehyde-3-phosphate dehydrogenase. Reduction of Ca(2+)-ATPase protein levels and Ca(2+) transport activity to approximately 50% of control values followed with some delay, evidently as a consequence of a primary effect on transcription. Cytosolic Ca(2+) signaling kinetics, measured with a Ca(2+)-sensitive dye after electrical stimuli, were significantly altered in hypertrophic myocytes. However, the effect of PE hypertrophy on cytosolic Ca(2+) signaling kinetics was less prominent than observed in myocytes subjected to drastic SERCA2 downregulation with small interfering RNA or inhibition with thapsigargin (10 nM). We conclude that SERCA2 undergoes significant downregulation after hypertrophic stimuli, possibly due to lack of SERCA gene involvement by the hypertrophy transcriptional program. The consequence of SERCA2 downregulation on Ca(2+) signaling is partially compensated by alternate Ca(2+) transport mechanisms. These alterations may contribute to a gradual onset of functional failure in long-term hypertrophy. PMID- 17287367 TI - ROS scavenging before 27 degrees C ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state. AB - We have shown that cold perfusion of hearts generates reactive oxygen and nitrogen species (ROS/RNS). In this study, we determined 1) whether ROS scavenging only during cold perfusion before global ischemia improves mitochondrial and myocardial function, and 2) which ROS leads to compromised cardiac function during ischemia and reperfusion (I/R) injury. Using fluorescence spectrophotometry, we monitored redox balance (NADH and FAD), O(2)(*-) levels and mitochondrial Ca(2+) (m[Ca(2+)]) at the left ventricular wall in 120 guinea pig isolated hearts divided into control (Con), MnTBAP (a superoxide dismutase 2 mimetic), MnTBAP (M) + catalase (C) + glutathione (G) (MCG), C+G (CG), and N(G) nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) groups. After an initial period of warm perfusion, hearts were treated with drugs before and after at 27 degrees C. Drugs were washed out before 2 h at 27 degrees C ischemia and 2 h at 37 degrees C reperfusion. We found that on reperfusion the MnTBAP group had the worst functional recovery and largest infarction with the highest m[Ca(2+)], most oxidized redox state and increased ROS levels. The MCG group had the best recovery, the smallest infarction, the lowest ROS level, the lowest m[Ca(2+)], and the most reduced redox state. CG and L-NAME groups gave results intermediate to those of the MnTBAP and MCG groups. Our results indicate that the scavenging of cold-induced O(2)(*-) species to less toxic downstream products additionally protects during and after cold I/R by preserving mitochondrial function. Because MnTBAP treatment showed the worst functional return along with poor preservation of mitochondrial bioenergetics, accumulation of H(2)O(2) and/or hydroxyl radicals during cold perfusion may be involved in compromised function during subsequent cold I/R injury. PMID- 17287369 TI - Splitting and pill splitting. PMID- 17287368 TI - Thiol-oxidant monochloramine mobilizes intracellular Ca2+ in parietal cells of rabbit gastric glands. AB - In Helicobacter pylori-induced gastritis, oxidants are generated through the interactions of bacteria in the lumen, activated granulocytes, and cells of the gastric mucosa. In this study we explored the ability of one such class of oxidants, represented by monochloramine (NH(2)Cl), to serve as agonists of Ca(2+) accumulation within the parietal cell of the gastric gland. Individual gastric glands isolated from rabbit mucosa were loaded with fluorescent reporters for Ca(2+) in the cytoplasm (fura-2 AM) or intracellular stores (mag-fura-2 AM). Conditions were adjusted to screen out contributions from metal cations such as Zn(2+), for which these reporters have affinity. Exposure to NH(2)Cl (up to 200 microM) led to dose-dependent increases in intracellular Ca(2+) concentration ([Ca(2+)](i)), in the range of 200-400 nM above baseline levels. These alterations were prevented by pretreatment with the oxidant scavenger vitamin C or a thiol-reducing agent, dithiothreitol (DTT), which shields intracellular thiol groups from oxidation by chlorinated oxidants. Introduction of vitamin C during ongoing exposure to NH(2)Cl arrested but did not reverse accumulation of Ca(2+) in the cytoplasm. In contrast, introduction of DTT or N-acetylcysteine permitted arrest and partial reversal of the effects of NH(2)Cl. Accumulation of Ca(2+) in the cytoplasm induced by NH(2)Cl is due to release from intracellular stores, entry from the extracellular fluid, and impaired extrusion. Ca(2+) handling proteins are susceptible to oxidation by chloramines, leading to sustained increases in [Ca(2+)](i). Under certain conditions, NH(2)Cl may act not as an irritant but as an agent that activates intracellular signaling pathways. Anti-NH(2)Cl strategies should take into account different effects of oxidant scavengers and thiol-reducing agents. PMID- 17287371 TI - Innovations: psychotherapy: what creates and sustains commitment to the practice of psychotherapy? AB - Qualitative methods were used to identify characteristics of "passionately committed psychotherapists" (experienced psychotherapists who would describe themselves as having found the vocation that suits them better than any other) identified by peers in the Utah public mental health system. Six themes were identified by all 15 interviewees: balance between work and nonwork passions, adaptiveness and openness, transcendence (the belief that the practice of psychotherapy has extraordinary significance), intentional learning, personal fit with the role, and passion-supporting beliefs. These are characteristics that psychotherapists should nurture in themselves, that program supervisors should seek in potential employees, and that training programs should develop in trainees. PMID- 17287370 TI - Multifamily group treatment in a program for patients with first-episode psychosis: experiences from the TIPS project. AB - Psychoeducational multifamily group treatment based on the McFarlane model was implemented for adult patients experiencing a first episode of psychosis and for the families of 301 patients. Patients were participants in a research project in Norway and Denmark. Of 301 patients 246 were invited to participate and 147 agreed. Patients' reluctance to participate increased with age. Most had to wait between six and 12 months until a sufficient number was gathered to start a group. Treatment was well received by patients and families. Care should be taken to prevent a long delay before group commencement at this stressful period in the lives of patients and families. PMID- 17287372 TI - Personal accounts: invisible on judgment day. PMID- 17287374 TI - Don'T forget the workforce. PMID- 17287373 TI - Direct care workers in the National Drug Abuse Treatment Clinical Trials Network: characteristics, opinions, and beliefs. AB - OBJECTIVE: Individuals with direct care responsibilities in 348 drug abuse treatment units were surveyed to obtain a description of the workforce and to assess support for evidence-based therapies. METHODS: Surveys were distributed to 112 programs participating in the National Drug Abuse Treatment Clinical Trials Network (CTN). Descriptive analyses characterized the workforce. Analyses of covariance tested the effects of job category on opinions about evidence-based practices and controlled for the effects of education, modality (outpatient or residential), race, and gender. RESULTS: Women made up two-thirds of the CTN workforce. One-third of the workforce had a master's or doctoral degree. Responses from 1,757 counselors, 908 support staff, 522 managers-supervisors, and 511 medical staff (71% of eligible participants) suggested that the variables that most were most consistently associated with responses were job category (19 of 22 items) and education (20 of 22 items). Managers-supervisors were the most supportive of evidence-based therapies, and support staff were the least supportive. Generally, individuals with graduate degrees had more positive opinions about evidence-based therapies. Support for using medications and contingency management was modest across job categories. CONCLUSIONS: The relatively traditional beliefs of support staff could inhibit the introduction of evidence-based practices. Programs initiating changes in therapeutic approaches may benefit from including all employees in change efforts. PMID- 17287376 TI - Impact of splitting risperidone tablets on medication adherence and on clinical outcomes for patients with schizophrenia. AB - OBJECTIVE: Tablet splitting is a strategy aimed at reducing the cost of prescriptions. Some clinicians question whether patients with psychosis can understand and follow tablet-splitting instructions. The clinical impact of tablet splitting for individuals with severe mental illness is unknown. The research objectives were to determine whether risperidone tablet splitting is associated with changes in medication adherence, service utilization, or clinical outcomes. METHODS: The study was a retrospective analysis of administrative data from the New York-New Jersey region of the Veterans Health Administration for 2,436 individuals with schizophrenia or schizoaffective disorder who were prescribed risperidone from January 2001 through March 2003. Antipsychotic medication adherence was measured by medication possession ratio (MPR). Clinical outcomes included attendance at scheduled and unscheduled outpatient appointments and psychiatric and medical admission rates. RESULTS: The MPR increased from .83 to .90 (p<.001) after initiating tablet splitting. The rate of unscheduled mental health appointments increased significantly, particularly in the first 60 days after initiating splitting; attendance at scheduled outpatient mental health appointments was unchanged. Psychiatric admission and general medical admission rates were unchanged. CONCLUSIONS: The results provide some assurance that prescribing tablet splitting for patients with schizophrenia does not result in poor outcomes as measured by psychiatric and medical inpatient admissions. Increased MPRs and unscheduled appointments suggest that some patients may have experienced minor difficulty, especially early on (crumbled tablets or misunderstood splitting instructions). Patients should be instructed carefully when tablet splitting is prescribed. Future studies should address longer-term clinical outcomes and systemwide costs. PMID- 17287375 TI - Alcohol use disorders and the use of treatment services among college-age young adults. AB - OBJECTIVES: This study examined the utilization of and the perceived need for alcohol treatment services among college-age young adults (18-22 years) according to their educational status: full-time college students, part-time college students, noncollege students (currently in school with the highest grade level below college), and nonstudents (N=11,337). This breakdown of young adults had not been addressed previously. METHODS: Secondary analyses were conducted on data from the 2002 National Survey on Drug Use and Health. RESULTS: Full-time college students (21%) were as likely to have an alcohol use disorder as nonstudents (19%), but were more likely than part-time college students (15%) and noncollege students (12%). Only 4% of full-time college students with an alcohol use disorder received any alcohol services in the past year. Of those with an alcohol use disorder who did not receive treatment services, only 2% of full-time college students, close to 1% of part-time college students, and approximately 3% of young adults who were not in college reported a perceived need for alcohol treatment. Full-time college students were less likely than noncollege students to receive treatment for alcohol use disorders. All young adults with an alcohol use disorder were very unlikely to perceive a need for alcohol treatment or counseling. CONCLUSIONS: College-age adults have a high prevalence of alcohol use disorders, yet they are very unlikely to receive alcohol treatment or early intervention services or to perceive a need for such services. Underutilization of alcohol-related services among college-age young adults deserves greater research attention. PMID- 17287377 TI - Differential medication adherence among patients with schizophrenia and comorbid diabetes and hypertension. AB - OBJECTIVES: Global patient characteristics may affect adherence across all medications in a regimen, making medication-specific risk factors for adherence problems less important. Medication adherence was examined among patients with schizophrenia and comorbid physical conditions for consistency across therapeutic classes. METHODS: A national sample of veterans was selected according to use of medication for schizophrenia, diabetes, and hypertension (N=1,686). Adherence to each medication type was assessed with medication possession ratios (MPRs). Multilevel logistic models were used to study the impact of medication type on adherence, as well as the effect of other medication characteristics (such as the average days of medication supplied per refill), health service use, and patients' sociodemographic characteristics. RESULTS: Adherence was only modestly correlated across types of medication. Information about antipsychotic adherence explained only 13% and 16% of the variance in patients' antihypertensive and hypoglycemic MPRs, respectively. In unadjusted analyses, patients were more likely to have poorer adherence (MPR less than .8) to their antipsychotics (35%) than to their hypoglycemic (29%) or antihypertensive medications (26%) (p<.001). However, when analyses controlled for the average days' supply and other regimen characteristics, hypoglycemic and antihypertensive medications were associated with an increased risk of poor adherence relative to antipsychotics (both adjusted odds ratios=1.5, p<.001). CONCLUSIONS: Patients with schizophrenia and comorbid physical conditions demonstrated important differences in adherence across medications in their regimen, reinforcing the importance of medication specific factors in determining adherence behavior. The lower levels of adherence observed for antipsychotics may be associated with the shorter refill intervals for these medications. PMID- 17287378 TI - Differences in lifetime use of services for mental health problems in six European countries. AB - OBJECTIVE: In Europe mental health services vary somewhat in the level of resources available and in their organization. The purpose of this study was to describe lifetime use of mental health services in six European countries, especially by individuals with a DSM-IV-defined psychiatric disorder (psychotic disorders were excluded), and to assess differences between countries as a function of resource availability. METHODS: Data were obtained from 8,796 noninstitutionalized adults of six European countries by computer-assisted interviews with the Composite International Diagnostic Interview, version 3.0. RESULTS: Lifetime consultation rates varied between countries and according to mental health status. For depression, lifetime consultation rates ranged from 37.0% in Italy to 71.0% in the Netherlands. Among users of services, general practitioners were the professionals most frequently consulted in all countries (64.2% on average), followed by psychiatrists (consultation ranged from 25.5% in the Netherlands to 43.8% in Spain) and psychologists (consultation ranged from 23.3% in France to 64.8% in the Netherlands). The lowest rates were in the countries with the lowest availability of professionals, but the countries with the highest density of professionals did not necessarily have the highest consultation rates. CONCLUSIONS: Although there are important differences in mental health care between European countries, they seem to be only partially related to differences in overall health care provision. PMID- 17287379 TI - Reductions in postdischarge suicide after deinstitutionalization and decentralization: a nationwide register study in Finland. AB - OBJECTIVE: This study analyzed trends in suicides occurring after a psychiatric hospitalization during more than a decade of significant structural changes in mental health services in Finland-that is, deinstitutionalization, downsizing of inpatient care, and decentralization. METHODS: Retrospective register data on completed suicides and psychiatric inpatient treatments were collected for the periods 1985-1991 and 1995-2001, representing service provision before and after significant structural changes. The data were used to produce an estimate for a change in postdischarge suicide risk. RESULTS: In both periods, a fifth of suicide victims had been psychiatrically hospitalized within the preceding year. Among persons hospitalized, the risk of suicide was greater in 1985-1991 than in 1995-2001 for both one week after discharge (risk ratio [RR]=1.50, 95% confidence interval [CI]=1.38-1.62) and one year after discharge (RR=1.25, CI=1.19-1.30). When types of disorders were analyzed separately, the relative risk of suicide one year postdischarge for those hospitalized in the earlier period was greater for patients with schizophrenia (RR=1.26, CI=1.17-1.36) and patients with affective disorders (RR=1.60, CI=1.48-1.73). In parallel with general development of inpatient psychiatric services, in 1995-2001 the inpatient treatment periods preceding suicides were significantly shorter (a mean+/-SD of 45+/-340 days in 1995-2001, compared with a mean of 98+/-558 days in 1985-1991), the number of individual patients treated in the hospital for schizophrenia spectrum disorders was lower (26% compared with 36%), and the number treated for affective disorders was higher (45% compared with 35%). CONCLUSIONS: The restructuring and downsizing of mental health services was not associated with any increase in suicides immediately (one week) or one year postdischarge. Instead, the risk of these suicides decreased significantly between the two time periods among several diagnostic categories. Although the role of psychiatric hospitalization in general may have changed over time, patients who are hospitalized now may be less suicidal after discharge. Our results indicate, in terms of postdischarge suicides, that the downsizing of psychiatric hospitals has been a success. However, there is still a substantial need for better recognition of suicidal risk among psychiatric patients. PMID- 17287380 TI - Consent form readability and educational levels of potential participants in mental health research. AB - OBJECTIVES: Poor readability of informed consent forms has been a persistent problem in clinical research. The low educational attainments of many patients with mental illness might suggest a still greater problem in mental health settings. To explore this potential disparity, this study sought to determine whether the informed consent forms used in research approved by the Massachusetts Department of Mental Health were written at a grade level that was higher than that achieved by potential study participants. METHODS: The readability (grade level necessary to read text) of informed consent forms for 154 studies was calculated with several standard formulas. Readability scores were stratified on the basis of the risk level of the study from which the consent form was taken. These data were then compared with data on the maximum attained grade level of potential participants aged 19 years or older. RESULTS: The overall mean readability scores for the informed consent forms, as determined by the four methods, ranged from grade levels 12 to 14.5. Furthermore, the mean readability scores increased with higher risk levels of the studies. Approximately 35% of potential participants had not graduated from high school, 37% had graduated from high school or obtained a GED, and 28% had some education beyond the 12th grade. CONCLUSIONS: These data demonstrate poor readability of informed consent forms used in research approved by the Massachusetts Department of Mental Health and highlight a mismatch between consent form readability and the educational level of potential study participants. The findings suggest that methods of reducing the complexity of forms, as part of improving the overall consent process, are much needed. PMID- 17287381 TI - Psychotic disorders, eating habits, and physical activity: who is ready for lifestyle changes? AB - OBJECTIVES: Significant weight gain is a serious side effect of many antipsychotic medications, yet successful strategies for significant weight loss are lacking. The transtheoretical model for weight management can be used to identify people who are ready to change (contemplation-preparation group) their eating habits and physical activity. This study compared characteristics of patients in Canada who had a psychotic disorder and were ready to make lifestyle changes with characteristics of patients who were not considering lifestyle changes. METHODS: Participants were surveyed to determine their stages of change for eating habits and physical activity, and various characteristics were measured, including body mass index, body image, nutritional intake, and level of physical activity. RESULTS: A total of 101 participants (64 men) (mean+/-SD age 35+/-11 years) were taking antipsychotic medications. Seventy-one percent had schizophrenia spectrum disorders, and 15% had affective psychosis. The prevalence of patients identified as being ready for change was higher than expected: 68% for eating habits and 54% for physical activity. Participants who were ready to change eating habits were also ready to change physical activity habits (p<.04). Stages of change for eating habits were associated with body mass index (p<.004), whereas stages of change for physical activity were associated with self-reported vigorous (p<.001) and moderate (p<.005) physical activity but not mild physical activity. CONCLUSIONS: Clinicians may help patients develop healthier eating and physical activity habits by using the transtheoretical model, because it identifies patients who are ready to change to healthier lifestyle strategies and may help patients with antipsychotic-induced weight gain. PMID- 17287382 TI - Use of qualitative methods to explore the quality-of-life construct from a consumer perspective. AB - OBJECTIVE: This study explored the construct of quality of life from the perspective of adults diagnosed as having severe and persistent mental illness, such as schizophrenia. METHODS: Qualitative research strategies, specifically in depth interviews (N=18) and focus groups (N=35), were used to collect data. Interviews and focus groups took place in hospitals, community clinics, community agencies, and clients' homes. A convenience, snowball sampling strategy was utilized. RESULTS: Analysis using the constant comparative method resulted in the identification of two dominant themes. These themes permeated the results, crossed all domains, influenced the linkages between domains, and clearly influenced how individuals frame their expectations regarding quality of life. The first theme was the presence of stigma and its effects on everyday life and future planning, and the second was the pervasive fear of the return of major positive symptoms of psychosis, such as hallucinations, delusions, and general loss of contact with reality. In addition, four quality-of-life domains were identified-the experience of illness, relationships, occupation, and sense of self. CONCLUSIONS: Many persons with mental illness simply wish for the basics in life-mental and physical health, supportive relationships, meaningful occupations, and a positive sense of self-believing that acquisition of these basics will lead to a more satisfactory quality of life. Ensuring that they are able to obtain the basics requires action on their part, by those who support them, by service providers that interact with them, and by a more accepting society. PMID- 17287383 TI - Correlates of adverse childhood events among adults with schizophrenia spectrum disorders. AB - OBJECTIVE: Multiple studies have found that childhood adversity is related to a range of poor mental health, substance abuse, poor physical health, and poor social functioning outcomes in the general population of adults. However, despite the high rates of childhood adversity in schizophrenia, the clinical correlates of these events have not been systematically evaluated. This study evaluated the relationship between adverse experiences in childhood and functional, clinical, and health outcomes among adults with schizophrenia. METHODS: The authors surveyed 569 adults with schizophrenia regarding adverse childhood events (including physical abuse, sexual abuse, parental mental illnesses, loss of a parent, parental separation or divorce, witnessing domestic violence, and foster or kinship care). The relationships between cumulative exposure to these events and psychiatric, physical, and functional outcomes were evaluated. RESULTS: Increased exposure to adverse childhood events was strongly related to psychiatric problems (suicidal thinking, hospitalizations, distress, and posttraumatic stress disorder), substance abuse, physical health problems (HIV infection), medical service utilization (physician visits), and poor social functioning (homelessness or criminal justice involvement). CONCLUSIONS: The findings extend the results of research in the general population by suggesting that childhood adversity contributes to worse mental health, substance abuse, worse physical health, and poor functional outcomes in schizophrenia. PMID- 17287384 TI - The genomic era and serious mental illness: a potential application for psychiatric genetic counseling. AB - Genetic counseling is an important clinical service that is routinely offered to families affected by genetic disorders or by complex disorders for which genetic testing is available. It is not yet routinely offered to individuals with serious mental illnesses and their families, but recent findings that beliefs about the cause of mental illness can affect an individual's adaptation to the illness suggest that genetic counseling may be a useful intervention for this population. In a genetic counseling session the counselor discusses genetic and environmental contributors to disease pathogenesis; helps individuals explore conceptions, fears, and adaptive strategies; and provides nondirective support for decision making. Expected outcomes may include reductions in fear, stigma, and guilt associated with a psychiatric diagnosis; improvements in adherence to prescribed medications; declines in risk behaviors; and reductions in misconceptions about the illness. The authors endorse a multidisciplinary approach in which a psychiatrist and genetic counselor collaborate to provide comprehensive psychiatric genetic counseling. PMID- 17287385 TI - The importance of holiday trips for people with chronic mental health problems. AB - Although research findings point to the importance of leisure activities for people with severe mental illness, there is no research into the specific effects of holiday trips. This Open Forum describes the experience of going on holiday trips for people with chronic mental health problems in the Netherlands. A qualitative research design was used. Material for the research was collected by participant observation on two trips and in-depth interviews of 11 travelers and four psychiatric nurses who accompanied the travelers. The trips contributed to rehabilitation by promoting and supporting, among other things, community participation, social relations, skill development, and new perceptions of identity. The trips also helped travelers to maintain balance in everyday life. For the nurses the trips provided a learning environment outside of medical institutions. PMID- 17287386 TI - How are substance use disorders addressed in VA psychiatric and primary care settings? Results of a national survey. AB - OBJECTIVE: This study examined interventions for substance use disorders within the Department of Veterans Affairs (VA) psychiatric and primary care settings. METHODS: National random samples of 83 VA psychiatry program directors and 102 primary care practitioners were surveyed by telephone. The survey assessed screening practices to detect substance use disorders, protocols for treating patients with substance use disorders, and available treatments for substance use disorders. RESULTS: Respondents reported extensive contact with patients with substance use problems. However, a majority reported being ill equipped to treat substance use disorders themselves; they usually referred such patients to specialty substance use disorder treatment programs. CONCLUSIONS: Offering fewer specialty substance use disorder services within the VA may be problematic: providers can refer patients to specialty programs only if such programs exist. Caring for veterans with substance use disorders may require increasing the capacity of and establishing new specialty programs or expanding the ability of psychiatric programs and primary care practitioners to provide such care. PMID- 17287387 TI - Relationship between diabetes and mortality among persons with co-occurring psychotic and substance use disorders. AB - OBJECTIVE: Individuals with diabetes and individuals with serious mental illness are more likely than the general population to die prematurely. The study examined the impact of diabetes on mortality among 197 individuals with co occurring psychotic and substance use disorders who participated in a randomized controlled study of integrated mental health and substance abuse treatment. METHODS: The authors examined Medicaid claims for evidence of diabetes and applied survival analyses to examine whether time from study entry until death was different for individuals with and without evidence of diabetes. RESULTS: Of individuals with co-occurring psychotic and substance use disorders, 21% had evidence of diabetes. In a 12-year period, 41% of those with evidence of diabetes died compared with 10% of those without evidence of diabetes. CONCLUSIONS: Interventions targeted for diabetes prevention and diabetes management are critical for persons with serious mental illness, particularly among those who also abuse substances. PMID- 17287389 TI - Identification of N-acetyltransferase 2 (NAT2) transcription start sites and quantitation of NAT2-specific mRNA in human tissues. AB - Human N-acetyltransferase 2 (NAT2) genetic polymorphism is associated with drug toxicity and/or carcinogenesis in various tissues. Knowledge of NAT2 gene structure and expression is critical for understanding these associations. Previous findings suggest that human NAT2 expression is highest in liver and gut but expressed at functional levels in other tissues. A sensitive and specific TaqMan reverse transcriptase-polymerase chain reaction (RT-PCR) assay with intron spanning primers was developed and used, together with a second TaqMan RT-PCR assay based on amplification of a NAT2 open reading frame (ORF) exon segment, to measure NAT2 mRNA in 29 different human tissues. Cap-dependent amplification of mRNA 5' termini and review of public database information were done to more precisely define the NAT2 promoter(s) and to validate the quantitative RT-PCR assay design. The great majority (40/41) of NAT2 liver cDNAs had 5' termini between 8682 and 8752 nucleotides upstream of the NAT2 ORF exon, and 34 of 40 5' termini were at the -8711 and -8716 adenines. All 59 NAT2 cDNAs with 5' termini in this vicinity, including 40 of the liver isolates and 19 cDNAs in public databases from liver and other sources, showed direct splicing to the ORF exon, with no other noncoding exon detected. NAT2 mRNA was highest in liver, small intestine, and colon and was readily detected in most other tissues, albeit at much lower levels. NAT2 expression in diverse human tissues provides further mechanistic support underlying associations between NAT2 genetic polymorphism, drug toxicity, and/or chemical carcinogenesis. PMID- 17287390 TI - Resveratrol in human hepatoma HepG2 cells: metabolism and inducibility of detoxifying enzymes. AB - trans-Resveratrol is a polyphenol present in several plant species. Its chemopreventive properties against several diseases have been largely documented. To validate a model for the study of the factors influencing its biological fate at the hepatic level, the metabolism and the efflux of resveratrol were studied in the human hepatoblastoma cell line, HepG2. Comparative high-performance liquid chromatography analysis of cell culture media before and after deconjugation showed that resveratrol was rapidly conjugated; at the concentration of 10 microM, it was entirely metabolized at 8 h of incubation. Two main resveratrol metabolites, monosulfate and disulfate, were identified by atmospheric pressure chemical ionization-mass spectrometry, thanks to their quasi-molecular ion and their characteristic fragmentation. To correlate with the auto-induction of resveratrol metabolism evidenced in HepG2 cells after a pretreatment for 48 h with 10 microM resveratrol, the inducibility of phase II enzymes by resveratrol was studied by real-time quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. Observed, in particular, were an increase in mRNA expression levels of three metabolizing enzymes, two isoforms of UDP glucuronosyltransferases, UGT1A1 and UGT2B7 (5-fold increased), and a sulfotransferase, ST1E1, in cells pretreated for 24 h with 10 microM resveratrol. These results were correlated with an increase in protein expression, especially after 48 h of treatment. On the other hand, the intracellular resveratrol retention in cells treated with MK571 (3-[[3-[2-(7-chloroquinolin-2 yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid), a multidrug resistance-associated protein inhibitor, strongly suggests the involvement of this ABC transporter family in the efflux of resveratrol conjugates from human liver. PMID- 17287391 TI - Addendum to "Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations: a medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology": public safety issues in patients with implantable defibrillators: a scientific statement from the American Heart Association and the Heart Rhythm Society. AB - OVERVIEW: In 1996, the American Heart Association developed a scientific statement entitled "Personal and Public Safety Issues Related to Arrhythmias That May Affect Consciousness: Implications for Regulation and Physician Recommendations." Since then, multiple trials have established the role of implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden cardiac death in patients at risk for life-threatening ventricular arrhythmias. OBJECTIVE: The issue of driving for patients with ICDs implanted for primary prevention was briefly discussed in the original statement, with the recommendation that such patients not be restricted from driving beyond the initial phase of healing. This scientific statement has been developed to extend the original 1996 recommendations and to provide specific recommendations on driving for individuals with ICDs implanted for primary prevention. SUMMARY OF RECOMMENDATIONS: (1) Patients receiving ICDs for primary prevention should be restricted from driving a private automobile for at least 1 week to allow for recovery from implantation of the defibrillator. Thereafter, these driving privileges should not be restricted in the absence of symptoms potentially related to an arrhythmia. (2) Patients who have received an ICD for primary prevention who subsequently receive an appropriate therapy for ventricular tachycardia or ventricular fibrillation, especially with symptoms of cerebral hypoperfusion, should then be considered to be subject to the driving guidelines previously published for patients who received an ICD for secondary prevention. (3) Patients with ICDs for primary prevention must be instructed that impairment of consciousness is a possible future event. (4) These recommendations do not apply to the licensing of commercial drivers. PMID- 17287392 TI - Neuronal and non-neuronal functions of the AP-3 sorting machinery. AB - Vesicles selectively exchange lipids, membrane proteins and luminal contents between organelles along the exocytic and endocytic routes. The repertoire of membrane proteins present in these vesicles is crucial for their targeting and function. Vesicle composition is determined at the time of their biogenesis by cytosolic coats. The heterotetrameric protein adaptor protein complex 3 (AP-3), a coat component, participates in the generation of a diverse group of secretory organelles and lysosome-related organelles. Recent work has shed light on the mechanisms that regulate AP-3 and the trafficking pathways controlled by this adaptor. Phenotypic analysis of organisms carrying genetic deficiencies in the AP 3 pathway highlight its role regulating the targeting of lysosomal, melanosomal and synaptic vesicle-specific membrane proteins. Synaptic vesicles from AP-3 deficient mice possess altered levels of neurotransmitter and ion transporters, molecules that ultimately define the type and amount of neurotransmitter stored in these vesicles. These findings reveal a complex picture of how AP-3 functions in multiple tissues, including neuronal tissue, and expose potential links between endocytic sorting mechanisms and the pathogenesis of psychiatric disorders such as schizophrenia. PMID- 17287393 TI - Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs. AB - Cargo selectivity is a hallmark of clathrin-mediated endocytosis. A wide range of structurally unrelated internalization signals specify the preferential clustering of transmembrane cargo into clathrin coats forming on the plasma membrane. Intriguingly, the classical endocytic adaptor AP-2 appears to recognize only a subset of these endocytic sorting signals. New data now reveal the molecular basis for recognition of other internalization signals, including post translationally appended ubiquitin, by clathrin-coat-associated sorting proteins (CLASPs). Curiously, structurally related ubiquitin-recognition modules are shared by select CLASPs and the 26S proteasome, and recent work indicates that both display similar requirements for ubiquitin binding. During endocytosis, these modules engage oligoubiquitylated cargo in the form of polyubiquitin chains and/or multiple single ubiquitin molecules appended to different acceptor lysines. Functional separation between clathrin-mediated endocytosis and proteasome-dependent proteolysis is probably ensured by temporally regulated, local assembly of ubiquitin-tagged membrane cargo at sorting stations on the cell surface, shielding ubiquitin sorting signals from the proteasome. Thus, an expanded repertoire of CLASPs couples the process of clathrin-coat assembly with high-fidelity incorporation of assorted, cargo-specific sorting signals. PMID- 17287394 TI - Evolution of a tumorigenic property conferred by glycophosphatidyl-inositol membrane anchors of carcinoembryonic antigen gene family members during the primate radiation. AB - GPI membrane anchors of cell surface glycoproteins have been shown to confer functional properties that are different from their transmembrane (TM)-anchored counterparts. For the human carcinoembryonic antigen (CEA) family, a subfamily of the immunoglobulin superfamily, conversion of the mode of membrane linkage from TM to GPI confers radical changes in function: from tumor suppression or neutrality toward inhibition of differentiation and anoikis and distortion of tissue architecture, thereby contributing to tumorigenesis. We show here that GPI anchorage in the CEA family evolved twice independently in primates, very likely from more primitive TM anchors, by different packages of mutations. Both mutational packages, one package found in many primates, including humans, and a second, novel package found only in the Cebidae radiation of New World monkeys, give rise to efficiently processed GPI-linked proteins. Both types of GPI anchors mediate inhibition of cell differentiation. The estimated rate of nonsynonymous mutations (Ka) in the anchor-determining domain for conversion from TM to GPI anchorage in the CEA family that were fixed during evolution in these primates is 7 times higher than the average Ka in primates, indicating positive selection. These results suggest therefore that the functional changes mediated by CEA GPI anchors, including the inhibition of differentiation and anoikis, could be adaptive and advantageous. PMID- 17287395 TI - Apical epidermal growth factor receptor signaling: regulation of stretch dependent exocytosis in bladder umbrella cells. AB - The apical surface of polarized epithelial cells receives input from mediators, growth factors, and mechanical stimuli. How these stimuli are coordinated to regulate complex cellular functions such as polarized membrane traffic is not understood. We analyzed the requirement for growth factor signaling and mechanical stimuli in umbrella cells, which line the mucosal surface of the bladder and dynamically insert and remove apical membrane in response to stretch. We observed that stretch-stimulated exocytosis required apical epidermal growth factor (EGF) receptor activation and that activation occurred in an autocrine manner downstream of heparin-binding EGF-like growth factor precursor cleavage. Long-term changes in apical exocytosis depended on protein synthesis, which occurred upon EGF receptor-dependent activation of mitogen-activated protein kinase signaling. Our results indicate a novel physiological role for the EGF receptor that couples upstream mechanical stimuli to downstream apical EGF receptor activation that may regulate apical surface area changes during bladder filling. PMID- 17287396 TI - Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascades. AB - During embryonic lymphatic development, a homeobox transcription factor Prox1 plays important roles in sprouting and migration of a subpopulation of blood vessel endothelial cells (BECs) toward VEGF-C-expressing cells. However, effects of Prox1 on endothelial cellular behavior remain to be elucidated. Here, we show that Prox1, via induction of integrin alpha9 expression, inhibits sheet formation and stimulates motility of endothelial cells. Prox1-expressing BECs preferentially migrated toward VEGF-C via up-regulation of the expression of integrin alpha9 and VEGF receptor 3 (VEGFR3). In mouse embryos, expression of VEGFR3 and integrin alpha9 is increased in Prox1-expressing lymphatic endothelial cells (LECs) compared with BECs. Knockdown of Prox1 expression in human LECs led to decrease in the expression of integrin alpha9 and VEGFR3, resulting in the decreased chemotaxes toward VEGF-C. These findings suggest that Prox1 plays important roles in conferring and maintaining the characteristics of LECs by modulating multiple signaling cascades and that integrin alpha9 may function as a key regulator of lymphangiogenesis acting downstream of Prox1. PMID- 17287397 TI - Conserved actin cysteine residues are oxidative stress sensors that can regulate cell death in yeast. AB - Actin's functional complexity makes it a likely target of oxidative stress but also places it in a prime position to coordinate the response to oxidative stress. We have previously shown that the NADPH oxidoreductase Oye2p protects the actin cytoskeleton from oxidative stress. Here we demonstrate that the physiological consequence of actin oxidation is to accelerate cell death in yeast. Loss of Oye2p leads to reactive oxygen species accumulation, activation of the oxidative stress response, nuclear fragmentation and DNA degradation, and premature chronological aging of yeast cells. The oye2Delta phenotype can be completely suppressed by removing the potential for formation of the actin C285 C374 disulfide bond, the likely substrate of the Oye2p enzyme or by treating the cells with the clinically important reductant N-acetylcysteine. Because these two cysteines are coconserved in all actin isoforms, we theorize that we have uncovered a universal mechanism whereby actin helps to coordinate the cellular response to oxidative stress by both sensing and responding to oxidative load. PMID- 17287398 TI - Muscle satellite cells and endothelial cells: close neighbors and privileged partners. AB - Genetically engineered mice (Myf5nLacZ/+, Myf5GFP-P/+) allowing direct muscle satellite cell (SC) visualization indicate that, in addition to being located beneath myofiber basal laminae, SCs are strikingly close to capillaries. After GFP(+) bone marrow transplantation, blood-borne cells occupying SC niches previously depleted by irradiation were similarly detected near vessels, thereby corroborating the anatomical stability of juxtavascular SC niches. Bromodeoxyuridine pulse-chase experiments also localize quiescent and less quiescent SCs near vessels. SCs, and to a lesser extent myonuclei, were nonrandomly associated with capillaries in humans. Significantly, they were correlated with capillarization of myofibers, regardless to their type, in normal muscle. They also varied in paradigmatic physiological and pathological situations associated with variations of capillary density, including amyopathic dermatomyositis, a unique condition in which muscle capillary loss occurs without myofiber damage, and in athletes in whom capillaries increase in number. Endothelial cell (EC) cultures specifically enhanced SC growth, through IGF-1, HGF, bFGF, PDGF-BB, and VEGF, and, accordingly, cycling SCs remained mainly juxtavascular. Conversely, differentiating myogenic cells were both proangiogenic in vitro and spatiotemporally associated with neoangiogenesis in muscular dystrophy. Thus, SCs are largely juxtavascular and reciprocally interact with ECs during differentiation to support angio-myogenesis. PMID- 17287399 TI - Subcellular relocalization of a trans-acting factor regulates XIAP IRES-dependent translation. AB - Translation of the X-linked inhibitor of apoptosis (XIAP) proceeds by internal ribosome entry site (IRES)-mediated initiation, a process that is physiologically important because XIAP expression is essential for cell survival under conditions of compromised cap-dependent translation, such as cellular stress. The regulation of internal initiation requires the interaction of IRES trans-acting factors (ITAFs) with the IRES element. We used RNA-affinity chromatography to identify XIAP ITAFs and isolated the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). We find that hnRNP A1 interacts with XIAP IRES RNA both in vitro and in vivo and that hnRNP A1 negatively regulates XIAP IRES activity. Moreover, XIAP IRES dependent translation is significantly reduced when hnRNP A1 accumulates in the cytoplasm. Osmotic shock, a cellular stress that causes cytoplasmic accumulation of hnRNP A1, also leads to a decrease in XIAP levels that is abrogated by knockdown of hnRNP A1 expression. These results suggest that the subcellular localization of hnRNP A1 is an important determinant of its ability to negatively regulate XIAP IRES activity, suggesting that the subcellular distribution of ITAFs plays a critical role in regulating IRES-dependent translation. Our findings demonstrate that cytoplasmic hnRNP A1 is a negative regulator of XIAP IRES-dependent translation, indicating a novel function for the cytoplasmic form of this protein. PMID- 17287400 TI - Death receptor-induced apoptosis reveals a novel interplay between the chromosomal passenger complex and CENP-C during interphase. AB - Despite the fact that the chromosomal passenger complex is well known to regulate kinetochore behavior in mitosis, no functional link has yet been established between the complex and kinetochore structure. In addition, remarkably little is known about how the complex targets to centromeres. Here, in a study of caspase-8 activation during death receptor-induced apoptosis in MCF-7 cells, we have found that cleaved caspase-8 rapidly translocates to the nucleus and that this translocation is correlated with loss of the centromere protein (CENP)-C, resulting in extensive disruption of centromeres. Caspase-8 activates cytoplasmic caspase-7, which is likely to be the primary caspase responsible for cleavage of CENP-C and INCENP, a key chromosomal passenger protein. Caspase-mediated cleavage of CENP-C and INCENP results in their mislocalization and the subsequent mislocalization of Aurora B kinase. Our results demonstrate that the chromosomal passenger complex is displaced from centromeres as a result of caspase activation. Furthermore, mutation of the primary caspase cleavage sites of INCENP and CENP-C and expression of noncleavable CENP-C or INCENP prevent the mislocalization of the passenger complex after caspase activation. Our studies provide the first evidence for a functional interplay between the passenger complex and CENP-C. PMID- 17287401 TI - Protean agonism at the dopamine D2 receptor: (S)-3-(3-hydroxyphenyl)-N propylpiperidine is an agonist for activation of Go1 but an antagonist/inverse agonist for Gi1,Gi2, and Gi3. AB - A range of ligands displayed agonism at the long isoform of the human dopamine D(2) receptor, whether using receptor-G protein fusions or membranes of cells in which pertussis toxin-resistant mutants of individual Galpha(i)-family G proteins could be expressed in an inducible fashion. Varying degrees of efficacy were observed for individual ligands as monitored by their capacity to load [(35)S]GTPgammaS onto each of Galpha(i1),Galpha(i2),Galpha(i3), and Galpha(o1). By contrast, (S)-(-)-3-(3-hydroxyphenyl)-N-propylpiperidine was a partial agonist when Galpha(o1) was the target G protein but an antagonist/inverse agonist at Galpha(i1),Galpha(i2), and Galpha(i3). In ligand binding assays, dopamine identified both high- and low-affinity states at each of the dopamine D(2) receptor-G protein fusion proteins, and the high-affinity state was eliminated by guanine nucleotide. (S)-(-)-3-(3-hydroxyphenyl)-N-propylpiperidine bound to an apparent single state of the constructs in which the D(2) receptor was fused to Galpha(i1),Galpha(i2), or Galpha(i3). However, it bound to distinct high- and low affinity states of the D(2) receptor-Galpha(o1) fusion, with the high-affinity state being eliminated by guanine nucleotide. Likewise, although dopamine identified guanine nucleotide-sensitive high-affinity states of the D(2) receptor when expression of pertussis toxin-resistant forms of each of Galpha(i1), Galpha(i2), Galpha(i3), and Galpha(o1) was induced, (S)-(-)-3-(3-hydroxyphenyl)-N propylpiperidine identified a high-affinity site only in the presence of Galpha(o1). p-Tyramine displayed a protean ligand profile similar to that of (S) (-)-3-(3-hydroxyphenyl)-N-propylpiperidine but with lower potency. These results demonstrate (S)-(-)-3-(3-hydroxyphenyl)-N-propylpiperidine to be a protean agonist at the D(2) receptor and may explain in vivo actions of this ligand. PMID- 17287402 TI - Solute-inhibitor interactions in the plasmodial surface anion channel reveal complexities in the transport process. AB - Human red blood cells infected with the malaria parasite Plasmodium falciparum have markedly increased permeabilities to diverse organic and inorganic solutes. The plasmodial surface anion channel (PSAC), recently identified with electrophysiological methods, contributes to the uptake of many small solutes. In this study, we explored the effects of known PSAC antagonists on transport of different solutes. We were surprised to find that the transport of two solutes, phenyltrimethylammonium and isoleucine, was only partially inhibited by concentrations of three inhibitors that abolish sorbitol or alanine uptake. Residual uptake via endogenous transporters could not account for this finding because uninfected red blood cells (RBCs) do not have adequate permeability for these solutes. In infected RBCs, the residual uptake of these solutes could be abolished by higher concentrations of specific and nonspecific PSAC antagonists. Adding sorbitol or alanine, permeant solutes that do not exhibit residual uptake, could also abolish it. The residual uptake did not exhibit anomalous mole fraction behavior and had a steep activation energy. These observations exclude uptake via unrelated pathways and instead point to differences in how PSAC recognizes and transports various solutes. We propose a possible model that also may help explain the unique selectivity properties of PSAC. PMID- 17287403 TI - What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. AB - Prolactinoma is the most common pituitary tumour in adults. Macroprolactinomas, particularly in men, may occasionally exhibit a very aggressive clinical course as evidenced by progressive growth, invasion through bone into the sphenoid sinus, cavernous sinus, suprasellar region or the nasopharynx. Some may even progress to pituitary carcinoma with craniospinal or systemic metastases. Aggressive tumours have low cure rates despite appropriate medical and surgical treatment. The mechanisms underlying this aggressive biological behaviour have not yet been fully clarified. Recent immunohistochemical, molecular and genetic studies have provided some insight in this respect. Invasive prolactinomas may be associated with a high Ki-67/MIB-1 labelling index indicating increased cell proliferation, although this is not a universal finding. The AA polymorphism in the cyclin adenine (A)/guanine (G) gene is more frequently detected in invasive prolactinomas. Increased expression of the polysialylated neural cell adhesion molecule (NCAM) and reduced expression of the E-cadherin/catenin complex implies a contribution of altered cell-to-cell adhesion and cellular migration. Extracellular matrix components (ECM), matrix metalloproteinases (MMPs) and their inhibitors play important roles in the context of angiogenesis and invasion. The induction of fibroblast growth factor and vascular endothelial growth factor via oestrogen-induced overexpression of novel genes (PTTG, hst and Edpm5) enhance cell growth, proliferation and angiogenesis contributing to invasiveness in prolactinomas. Although mutations in proto-oncogenes like Ras are uncommon, loss of tumour suppressor genes at loci 11q13, 13q12-14, 10q and 1p seem to be associated with invasiveness. Of the described mechanisms, only reduced E cadherin/catenin expression and overexpression of hst gene seem to be relatively specific markers for prolactinoma invasiveness compared with other pituitary adenomas. Further research is needed to clarify the molecular mechanisms behind the aggressive course of some prolactinomas to predict those with a potentially poor clinical outcome, and to devise treatments that will eventually enable the cure of these challenging tumours. PMID- 17287405 TI - Hypogonadotropic hypogonadism in an adult female with a heterozygous hypomorphic mutation of SOX2. AB - OBJECTIVE: Heterozygous SOX2 mutations have recently been reported to cause isolated hypogonadotropic hypogonadism (HH), in addition to ocular and brain abnormalities. Here, we report a further case with a heterozygous hypomorphic SOX2 mutation and isolated HH. PATIENT: The patient was a 28-year-old Japanese female with congenital right anophthalmia and poor pubertal development, who was found to have HH by a gonadotropin-releasing hormone test (peak serum LH, 2.3 mIU/ml; peak serum FSH, 2.9 mIU/ml). Other pituitary hormones were normal. METHODS: We performed mutation analysis of SOX2 and functional studies of mutant SOX2 protein using the core enhancer sequence of the chicken delta-1-crystallin gene (DC5) and that of the mouse nestin gene (Nes30). RESULTS: A heterozygous missense mutation (224T > A, Leu75Gln) was identified in the DNA-binding domain. The mutant SOX2 protein had a severely reduced (approximately 10%) DNA-binding affinity and a markedly diminished (20-30%) transactivation potential with no dominant negative effect. CONCLUSIONS: The results provide further support for the positive role of SOX2 in the regulation of gonadotropin production. PMID- 17287404 TI - Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation. AB - OBJECTIVE: STAT5b is a component of the GH signaling pathway. Recently, we described a 31-year-old male patient (height, -5.9 SDS) with a novel homozygous inactivating mutation in the STAT5b gene. The purpose of this study is to describe the phenotype in detail, including GH secretion and immunological function. In addition, we report four family members of this patient, all heterozygous carriers of the mutation. DESIGN AND METHODS: Twenty-four hour GH and prolactin secretion characteristics were assessed by blood sampling at 10-min intervals. An IGF-I generation test was performed. Monocyte function was tested by stimulation of whole blood with lipopolysaccharide (LPS) in the presence or absence of Interferon-gamma (IFN-gamma). In addition, T cell function was determined by measuring proliferative responses of peripheral blood mononuclear cells (PBMC) after stimulation by various polyclonal activators and Interleukin-2 (IL-2). Clinical and biochemical characteristics were determined in the carriers of the mutation. RESULTS: GH secretory parameters were comparable with that of healthy male controls (mean fat percentage 25), but likely increased in relation to the patient's 40% body fat. The regularity of GH secretion was diminished. Prolactin secretion was increased by sixfold. The IGF-I generation test showed a small increase in IGF-I and IGF-binding protein-3 on lower GH doses and an increase in IGF-I to -2.4 SDS on the highest dose of GH. In vitro, IL-12p40, IL 10, and tumour necrosis factor-alpha (TNF-alpha) production rates by PBMC increased to values within the normal range upon stimulation of LPS. Heterozygous carriers of the mutation did not show abnormalities, although the height of the males was below the normal range. CONCLUSIONS: This report shows that GH and prolactin secretion were increased in this patient homozygous for a new STAT5b mutation. Although STAT5b plays a role in signaling within immune cells, clinical immunodeficiency is not an obligatory phenomenon of STAT5b deficiency per se. Heterozygous carriers of a STAT5b mutation show no signs of GH insensitivity. PMID- 17287406 TI - Thyroid hormone state and quality of life at long-term follow-up after randomized treatment of Graves' disease. AB - OBJECTIVE: In a 14-21 year follow-up of health-related quality of life (HRQL) outcome of 179 patients after randomized treatment of Graves' disease (GD) with surgical, medical or radioiodine, we found no differences. The HRQL for Graves' patients, however, was lower compared with a large age- and sex-matched Swedish reference population. We have now studied whether the reported HRQL-scores by Medical Outcome Study 36-item Short-Form Health Status Survey (SF36) and quality of life 2004 (QoL2004) answers were related to the thyroid hormone state of the patient. METHODS: This report comprises 91 of the original patients in which both the results of SF36 and QoL2004 questionnaire as well as serum thyroid hormones and current use of l-thyroxine treatment were available. RESULTS: A large number of the patients had low or undetectable serum TSH concentrations. SF36 scores and answers to QoL2004 questionnaires were not correlated to TSH levels or associated with suppressed TSH. A low free triiodothyronine was weakly associated with a low GH score (P < 0.02) and elevated thyrotropin receptor antibody with a low physical component summary (P < 0.02). CONCLUSION: HRQL do not seem to be influenced by the thyroid hormone state of the patient including subclinical thyrotoxicosis. It is possible that the personality of GD patients as such may have resulted both in the development of GD and lower HQRL scores later on in life. Alternatively, the generic SF36 may not be a proper instrument to detect relevant differences in HRQL related to the thyroid state. PMID- 17287407 TI - The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. AB - OBJECTIVE: The association between TSH and serum lipids in people with no apparent thyroid disease is insufficiently understood. We have studied the association between normal thyroid function, defined as TSH within the reference range of a general population, and concentrations of serum lipids. DESIGN: Cross sectional, population-based study with 30,656 individuals without known thyroid disease. METHODS: Using general linear models, we calculated mean concentrations of total serum cholesterol, low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, HDL cholesterol and triglycerides across categories of TSH. RESULTS: Within the reference range of TSH, there was a linear and significant (P for trend <0.001) increase in total serum cholesterol, LDL cholesterol, non-HDL cholesterol and triglycerides, and a linear decrease (P for trend <0.001) in HDL cholesterol with increasing TSH. Subgroup analyses showed statistically significant associations for all lipids in men above 50 years of age, and for triglycerides in all age groups. For women, associations were statistically significant in all age groups except for HDL cholesterol in women below 50 years of age. The associations with triglycerides and HDL cholesterol were stronger among overweight than normal weight individuals. CONCLUSIONS: Within the range of TSH that is considered clinically normal, we found that increasing level of TSH was associated with less favourable lipid concentrations. The association with serum lipids was linear across the entire reference range of TSH. PMID- 17287408 TI - Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer. AB - OBJECTIVE: Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). DESIGN: Hospital-based case-control study. METHODS: In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. RESULTS: In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH-IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. CONCLUSIONS: These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors. PMID- 17287409 TI - Effect of 2 years of high-dose growth hormone therapy on cognitive and psychosocial development in short children born small for gestational age. AB - OBJECTIVE AND DESIGN: Children born small for gestational age (SGA) are not only at risk for short stature, but also for neurodevelopmental and behavioral problems. In this study, we analyzed the effects of high-dose GH therapy on cognitive development and psychosocial functioning in 34 prepubertal (3-8 years) short SGA children, equally randomized into a GH-treated group (TRG) and an untreated group (UTRG). METHODS: At start and after 2 years, children underwent standardized tests measuring the intellectual abilities (Wechsler Preschool and Primary Scale of Intelligence-Revised, or Wechsler Intelligence Scale for Children-Revised); their parents completed a standardized questionnaire evaluating psychosocial functioning (Child Behavior Checklist; CBCL). RESULTS: At start, total IQ scores were significantly (P < 0.05) lower in the SGA group than in the general population: 32% of the SGA patients had scores below 85. After 2 years, IQ scores remained unchanged in the TRG, but increased significantly (P < 0.05) in the UTRG. After exclusion of children with developmental problems, however, no significant changes in IQ scores occurred in the UTRG as well as the TRG. At baseline, 24% (8/34) children had problematic CBCL total problems scores, equally distributed among the two groups; no significant changes in the different subscale scores occurred after 2 years. CONCLUSION: No beneficial effect of 2 years of GH therapy on cognitive and behavioral profile could be observed in a cohort of rather young short SGA children presenting a variable degree of developmental delay and behavioral problems. Subsequent follow-up could reveal potential long-term effects of GH therapy on development and behavior. PMID- 17287410 TI - Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. AB - In 1996, the German Registry of Pituitary Tumors was founded by the Pituitary Section of the German Society of Endocrinology as a reference center for collection and consultant pathohistological studies of pituitary tumors. The experiences of the first 10 years of this registry based on 4122 cases will herein be reported. The data supplement former collections of the years 1970-1995 with 3480 surgically removed tumors or lesions of the pituitary region. The cases were studied using histology, immunostainings and in some cases also molecular pathology or electron microscopy. The adenomas were classified according to the current World Health Organization classification in the version of 2004. From 1996 on 3489 adenomas (84.6%), 5 pituitary carcinomas (0.12%), 133 craniopharyngiomas (3.2%), 39 meningiomas (0.94%), 25 metastases (0.6%), 22 chordomas (0.5%), 115 cystic non-neoplastic lesions (2.8%), and 46 inflammatory lesions (1.1%, 248 other lesions or normal tissue (6.0%)) were collected by us. The adenomas (100%) were classified into densely granulated GH cell adenomas (9.2%), sparsely granulated GH cell adenomas (6.3%), sparsely granulated prolactin (PRL) cell adenomas (8.9%), densely granulated PRL cell adenomas (0.3%), mixed GH/PRL cell adenomas (5.2%), mammosomatotropic adenomas (1.1%), acidophilic stem cell adenomas (0.2%), densely granulated ACTH cell adenomas (7.2%), sparsely granulated ACTH cell adenomas (7.9%), Crooke cell adenomas (0.03%), TSH cell adenomas (1.5%), FSH/LH cell adenomas (24.8%), null cell adenomas (19.3%), null cell adenoma, oncocytic variant (5.8%), and plurihormonal adenomas (1.3%). Following the WHO classification of 2004, the new entity 'atypical adenoma' was found in 12 cases in 2005. Various prognostic parameters and clinical implications are discussed. PMID- 17287411 TI - The natural course of non-functioning pituitary macroadenomas. AB - OBJECTIVE: The natural history of non-functioning pituitary macroadenomas (NFMA) has not been completely elucidated. Therefore, we evaluated pituitary function, visual fields, and tumor size during long-term follow-up of non-operated patients with NFMA. DESIGN: Follow-up study. PATIENTS: Twenty-eight patients (age 55 +/- 3 years) with NFMA, not operated after initial diagnosis, were included. RESULTS: Initial presentation was pituitary insufficiency in 44%, visual field defects in 14%, apoplexy in 14%, and chronic headache in 7% of the patients. The duration of follow-up was 85 +/- 13 months. Radiological evidence of tumor growth was observed in 14 out of 28 patients (50%) after duration of follow-up of 118 +/- 24 months. Six patients (21%) were operated, because tumor growth was accompanied by visual field defects. Visual impairments improved in all the cases after transsphenoidal surgery. Spontaneous reduction in tumor volume was observed in eight patients (29%). No independent predictors for increase or decrease in tumor volume could be found by regression analysis. CONCLUSION: Observation alone is a safe alternative for transsphenoidal surgery in selected NFMA patients, without the risk of irreversibly compromising visual function. PMID- 17287412 TI - Effectiveness of long-term cabergoline treatment for giant prolactinoma: study of 12 men. AB - OBJECTIVE: To review our experience with cabergoline, a D2-selective dopamine agonist, for the treatment of giant prolactinomas. DESIGN: A retrospective case series; descriptive statistics. METHODS: The study group included 12 men aged 24 52 years (mean 39.2 years) treated for giant prolactinoma at our centers from 1997 to 2006. Cabergoline was started at a dose of 0.5 mg/three times a week and progressively increased as necessary to up to 7 mg/week. Patients were followed by hormone measurements, sellar magnetic resonance imaging, and visual examinations. RESULTS: In ten patients, cabergoline served as first-line therapy. The other two patients had previously undergone transsphenoidal partial tumor resection because of visual deterioration. Mean serum prolactin level before treatment was 14,393 +/- 14,579 ng/ml (range 2047-55,033 ng/ml; normal 5-17 ng/ml). Following treatment, levels normalized in ten men within 1-84 months (mean, 25.3 months) and decreased in the other two to 2-3 times of normal. Tumor diameter, which measured 40-70 mm at diagnosis, showed a mean maximal decrease of 47 +/- 21%; response was first noted about 6 months after the onset of treatment. Nine patients had visual field defects at diagnosis; vision returned to normal in three of them and improved in five. Testosterone levels, initially low in all patients, normalized in eight. There were no side effects of treatment. CONCLUSION: Cabergoline therapy appears to be effective and safe in men with giant prolactinomas. These findings suggest that cabergoline should be the first line therapy for aggressive prolactinomas, even in patients with visual field defects. PMID- 17287413 TI - Significant GH deficiency after long-term cure by surgery in adult patients with Cushing's disease. AB - OBJECTIVE: Impaired GH secretion usually accompanies Cushing's syndrome and a variable proportion of patients reportedly fail to recover normal GH secretion after successful treatment. This wide variability is most probably due to differences in the treatment (i.e. surgery and/or radiotherapy), timing of patient re-evaluation after surgery and dynamic tests employed to challenge GH secretion, and hinders a precise assessment of risk of GH deficiency after cure. The aim of the present study is to evaluate GH secretory status after long-term cure of Cushing's disease achieved by surgery alone. DESIGN AND METHODS: We studied 34 patients (27 females and 7 males, age range 21-68 years) formerly affected by Cushing's disease. Patients were studied 2-20 years (median 3.3 years) following remission of hypercortisolism; all patients underwent transsphenoidal surgery with the removal of an ACTH-secreting adenoma; repeat pituitary surgery for relapse was performed in two patients while bilateral adrenalectomy was necessary in two patients. In all subjects, the GH response to GHRH+arginine stimulation was evaluated. At the time of testing, 13 patients were still on steroid replacement therapy. RESULTS: In long-term surgical remission, 22 patients (65.0%) presented subnormal GH secretion; partial GH deficiency (GH peak <16.5 microg/l) was found in 11 patients and severe GH deficiency (GH peak <9 microg/l) in another 11. Male gender and length of hypercortisolism were risk factors for postsurgical GH deficiency. CONCLUSIONS: This study demonstrates the presence of GH deficiency in a high percentage of patients with Cushing's disease after long-term remission of hypercortisolism obtained by surgery alone. Male gender and length of hypercortisolism are the most significant predictors of postsurgical GH deficiency. This finding is significant as it highlights that even the most favourable therapeutical course, i.e. remission achieved by surgery alone, is accompanied by impaired GH secretion. Assessment of GH secretion is therefore recommended for all patients cured from Cushing's disease, even if not submitted to radiotherapy. Studies on the clinical impact of GH deficiency and the use of GH replacement therapy seem warranted in patients cured from Cushing's disease. PMID- 17287415 TI - Functional characterization of naturally occurring NR3C2 gene mutations in Italian patients suffering from pseudohypoaldosteronism type 1. AB - OBJECTIVE: The renal form of pseudohypoaldosteronism type 1 (PHA1) is a rare disease caused by mutations in the human mineralocorticoid receptor gene (NR3C2). DESIGN: Aim of the study was to analyze the NR3C2 gene in three Italian patients with clinical signs of renal PHA1 and to evaluate the distribution of the -2G > C, c.538A > G, and c.722C > T single nucleotide polymorphism (SNP) pattern in the PHA1 patients and in 90 controls of the same ethnic origin. METHODS: Analysis of the NR3C2 gene sequence and of the polymorphic SNP markers. Functional characterization of the detected novel NR3C2 mutations utilizing aldosterone binding assays and reporter gene transactivation assays. RESULTS: One novel nonsense (Y134X) and one novel frameshift (2125delA) mutation were detected. They exhibited no aldosterone binding and no transactivation abilities. No mutation was detected in the third patient. Haploinsufficiency of NR3C2 was ruled out by microsatellite analysis in this patient. The c.722T SNP was detected in 97% of alleles in the Italian population which is significantly different from the general German or US population. CONCLUSIONS: Molecular analysis of the NR3C2 gene in PHA1 patients is warranted to detect novel mutations in order to clarify the underlying genetic cause, which may extend the insight into relevant functional regions of the hMR protein. The effect the different distribution of the c.722T SNP is not clear to date. Further studies are necessary to provide evidence as to a possible advantage of a less sensitive hMR in southern countries. PMID- 17287414 TI - The usefulness of combined biochemical tests in the diagnosis of Cushing's disease with negative pituitary magnetic resonance imaging. AB - OBJECTIVE: The etiological diagnosis of ACTH-dependent Cushing's syndrome is often a problem. In fact, no endocrine or radiological examination can conclusively distinguish the ectopic from the pituitary source of disease. The aim of our study was to evaluate the role of stimulation and suppression endocrine tests in the diagnostic and therapeutic approach of patients with Cushing's disease (CD) and negative pituitary magnetic resonance imaging (MRI), considering their post-surgical outcome in comparison with patients with CD and positive MRI. PATIENTS AND METHODS: We retrospectively analyzed 31 patients (25 women and 6 men, median age 40 +/- 15 years) with a confirmed diagnosis of CD who underwent transsphenoidal pituitary surgery by the same neurosurgeon between 2001 and 2005. Preoperative endocrine assessment included corticotropin-releasing hormone (CRH), desmopressin (dDAVP), and overnight 8 mg dexamethasone suppression tests (8-DST) in all patients. Fifteen patients had a normal pituitary MRI and sixteen had a clearly evident pituitary microadenoma. Bilateral inferior petrosal sinus sampling (BIPSS) was performed in patients with discordant biochemical results or with signs and symptoms highly suggestive of an ectopic source of ACTH. Post-surgical median follow-up was 38.4 +/- 22.0 months. RESULTS: Among patients with negative MRI, 60% had concordant positive endocrine tests and underwent neurosurgery without other examinations. BIPSS was performed in three other patients prompted by discordant endocrine tests (negative dDAVP) and in two patients with clinical suspicion of ectopic disease. Among patients with positive MRI, 87% underwent neurosurgery without BIPSS that was performed in two patients because of negative concomitant response to dDAVP and CRH tests. A pituitary adenoma, confirmed by pathological examination, was found in 40 and 81% of patients with negative and positive MRI respectively (P<0.05), corticotroph hyperplasia resulted more frequent in the group with negative MRI. Remission rate was not different between patients with negative and positive MRI (73 and 75% respectively; P=0.61) and between patients with negative MRI who did not undergo BIPSS and patients with positive MRI (P=0.56). The recurrence rate was also similar between groups (P=0.64), but higher, although not statistically different (P=0.07) in patients with corticotroph hyperplasia at histology. CONCLUSIONS: An accurate evaluation of presurgical endocrine tests results enabled us to reduce the number of BIPSS in patients with a negative MRI without any fallout on their post-surgical outcome. In the hands of an expert pituitary surgeon, the outcome after surgeryand the subsequent recurrence rate are much the same in patients with negative or positive MRI. PMID- 17287416 TI - Tissue inhibitor of metalloproteinase-1 predicts adiposity in humans. AB - OBJECTIVE: Tissue inhibitor of metalloproteinase (TIMP)-1 is upregulated in fat of obese rodents and promotes adipose tissue development in these animals. However, it is unclear whether TIMP-1 independently predicts adiposity in humans and whether serum levels are increased in s.c. and visceral obesity. DESIGN: Twenty-four lean, 16 s.c. obese, and 20 visceral obese subjects were studied. METHODS: Plasma TIMP-1 concentrations were quantified using ELISAs and correlated to clinical parameters. RESULTS: Plasma TIMP-1 levels were significantly different between lean (156 +/- 42 microg/l), s.c. obese (186 +/- 52 microg/l), and visceral obese (198 +/- 42 microg/l) subjects (P < 0.01). Furthermore, TIMP-1 correlated positively with body mass index (BMI), waist-to-hip ratio (WHR), % body fat, fasting insulin, free fatty acids, cholesterol, leptin, interleukin-6, and negatively with adiponectin (P < 0.05). Moreover, TIMP-1 serum levels predicted % body fat but not WHR independent of age, sex, and plasma insulin. CONCLUSIONS: We demonstrate that increased TIMP-1 serum levels are found with increased adiposity in humans. PMID- 17287417 TI - Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study. AB - OBJECTIVE: Abdominal obesity, insulin resistance and compensatory hyperinsulinaemia play a central role in the pathogenesis of the polycystic ovary syndrome (PCOS). Abdominal adipose tissue is a source of adipokines, such as adiponectin and resistin, both of which may be involved in the development of insulin resistance and chronic inflammation in PCOS. Ghrelin, an important regulatory peptide of food intake, may also play a role in metabolic disturbances related to PCOS. The aim of this study was to examine the effects of 4 months of treatment with the insulin sensitizer rosiglitazone on plasma adiponectin, resistin and ghrelin levels in overweight women with PCOS. DESIGN: A randomised placebo-controlled study. METHODS: Thirty overweight/obese women with PCOS (body mass index>25 kg/m(2), mean age 29.1+/- 1.2 (S.E.M.) years) were randomly allocated to either rosiglitazone (Avandia, 4 mg twice a day) or placebo treatment. Plasma levels of adiponectin, resistin and ghrelin and their correlation to serum levels of insulin, C-peptide and steroid hormones, and insulin sensitivity (euglycaemic hyperinsulinaemic clamp) were assessed. RESULTS: Adiponectin and ghrelin levels correlated significantly with most metabolic markers of insulin resistance and with serum levels of DHEA and 17 hydroxyprogesterone. Plasma levels of adiponectin increased from 9.26+/-0.90 (S.E.M.) to 22.22+/-3.66 microg/ml (P<0.001) and those of resistin decreased from 12.57+/-1.63 to 9.21+/-0.53 ng/ml (P=0.009) at 4 months of treatment, but plasma ghrelin levels did not change. CONCLUSIONS: Rosiglitazone had beneficial effects on serum levels of adiponectin and resistin, suggesting that these adipocytokines may contribute to the improvement in insulin sensitivity observed during the treatment. PMID- 17287418 TI - Serum adiponectin levels, insulin resistance, and lipid profile in children born small for gestational age are affected by the severity of growth retardation at birth. AB - OBJECTIVE: Insulin resistance has been linked to intrauterine growth retardation (IUGR); adiponectin is a protein with insulin-sensitizing properties. This study was designed to test whether being born small for gestational age (SGA) has an effect on blood levels of adiponectin and leptin, insulin resistance parameters, and lipid profile in pre-puberty, taking into consideration the severity of IUGR. METHODS: Serum levels of adiponectin, leptin, total cholesterol (t-CHOL), high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, apolipoproteins A-1 (Apo A-1), Apo B and Apo E, lipoprotein(a) (Lp(a)), fasting glucose, and insulin (Ins), the homeostasis model assessment insulin resistance index (HOMA-IR) and anthropometric indices were evaluated in 70 children aged 6-8 years, born appropriate for gestational age (AGA; n = 35) and SGA (n = 35), matched for age, gender, height, and BMI. SGA children were divided into two subgroups according to the severity of IUGR: SGA<3rd percentile (n = 20), and SGA 3rd-10th percentile (n = 15). They were also subdivided in two subgroups, those with (n = 25) and those without (n = 10) catch-up growth, considering their actual height corrected for mid-parental height. RESULTS: SGA children had higher Ins and HOMA-IR than AGA children (Ins, 42 +/- 23 vs 32 +/- 11 pmol/l; HOMA-IR, 1.30 +/- 0.8 vs 0.92 +/- 0.3; P<0.05). No significant difference in serum leptin was found between the SGA and the AGA groups but adiponectin showed a trend to be higher in SGA children (13.6 +/- 5.7 vs 10.8 +/- 5.9 microg/ml respectively). SGA children without catch-up growth had higher adiponectin (15.6 +/- 8.5 microg/ml, P<0.05) than AGA children. Among the SGA children, the subgroup <3rd percentile had higher Lp(a) than the subgroup 3rd 10th percentile (P<0.05). An independent positive correlation between adiponectin and Lp(a) was observed in SGA children (R = 0.59, P<0.01). CONCLUSION: SGA children, although more insulin resistant, had similar or higher adiponectin levels than matched AGA children in pre-puberty. The severity of IUGR appears to affect their metabolic profile during childhood. PMID- 17287419 TI - Plasma resistin levels correlate with determinants of the metabolic syndrome. AB - OBJECTIVE: The role of resistin in insulin sensitivity and obesity is controversial. Some authors suggest that increased serum resistin levels are associated with obesity, visceral fat, insulin resistance, type 2 diabetes and inflammation, while others failed to observe such correlations. The aim of the present study was to investigate the relationship of plasma resistin levels with markers of the metabolic syndrome and atherosclerosis in a large population-based study. DESIGN AND PATIENTS: Plasma resistin levels were determined in 1090 subjects free of any medication selected from the PLIC study (designed to verify the presence of atherosclerotic lesions and progression intima-media thickness (IMT) in the common carotid artery in the general population) and related to the presence of obesity, metabolic syndrome, metabolic abnormalities, cardiovascular risk, and progression of IMT. RESULTS: Plasma resistin levels were highly positively correlated with triglycerides, waist circumference, waist/hip ratio, systolic blood pressure, and ApoAI/ApoB ratio, while they were inversely correlated with high density lipoprotein and ApoAI levels. This finding was gender specific (mainly in women). Plasma resistin levels were significantly higher in women with the metabolic syndrome compared with controls (4.90 (0.24) ng/ml vs 3.90 (0.11) ng/ml; P<0.01), while no difference was observed in obese subjects. Finally, plasma resistin levels were significantly correlated with cardiovascular risk calculated according to the Framingham algorithm (P<0.01). CONCLUSION: Plasma resistin levels are increased in presence of the metabolic syndrome and are associated with increased cardiovascular risk. PMID- 17287421 TI - A plea for transparency in Canada's "new government". PMID- 17287422 TI - New reproductive technology board belies expert selection process. PMID- 17287424 TI - Regulatory T cells and T cell depletion: role of immunosuppressive drugs. AB - Allogeneic immune responses are modulated by a subset of host T cells with regulatory function (Treg) contained within the CD4(+)CD25(high) subset. Evidence exists that Treg expand after peritransplantation lymphopenia, inhibit graft rejection, and induce and maintain tolerance. Little, however, is known about the role of Treg in the clinical setting. IL-2 and activation by T cell receptor engagement are instrumental to generate and maintain Treg, but the influence of immunosuppressants on Treg homeostasis in humans in vivo has not been investigated. This study monitored Treg phenotype and function during immune reconstitution in renal transplant recipients who underwent profound T cell depletion with Campath-1H and received sirolimus or cyclosporine (CsA) as part of their maintenance immunosuppressive therapy. CD4(+)CD25(high) cells that expressed FOXP3 underwent homeostatic peripheral expansion during immune reconstitution, more intense in patients who received sirolimus than in those who were given CsA. T cells that were isolated from peripheral blood long term after transplantation were hyporesponsive to alloantigens in both groups. In sirolimus- but not CsA-treated patients, hyporesponsiveness was reversed by Treg depletion. T cells from CsA-treated patients were anergic. Thus, lymphopenia and calcineurin dependent signaling seem to be primary mediators of CD4(+)CD25(high) Treg expansion in renal transplant patients. These findings will be instrumental in developing "tolerance permissive" immunosuppressive regimens in the clinical setting. PMID- 17287423 TI - DEC-205-mediated internalization of HIV-1 results in the establishment of silent infection in renal tubular cells. AB - HIV-1 infection of renal cells has been proposed to play a role in HIV-1 associated nephropathy. Renal biopsy data further suggest that renal tubular cells may serve as reservoir for HIV-1. The mechanism by which HIV-1 enters these cells has not been identified. Renal tubular cells do not express any of the known HIV-1 receptors, and our results confirmed lack of the expression of CD4, CCR5, CXCR4, DC-SIGN, or mannose receptors in tubular cells. The aim of this study, therefore, was to determine the mechanism that enables viral entry into renal tubular cells. An in vitro model was used to study the HIV-1 infection of human kidney tubular (HK2) cells and to identify the receptor that enables the virus to enter these cells. Results of these studies demonstrate that the C-type lectin DEC-205 acts as an HIV-1 receptor in HK2 cells. Interaction of HIV-1 with DEC-205 results in the internalization of the virus and establishment of a nonproductive infection. HIV-1-specific strong-stop DNA is detected in the infected HK2 cells for at least 7 d, and the virus can be transmitted in trans to sensitive target cells. HIV-1 entry is blocked by pretreatment with specific anti DEC-205 antibody. Moreover, expression of DEC-205 in cells that lack the DEC-205 receptors renders them susceptible to HIV-1 infection. These findings suggest that DEC-205 acts as an HIV-1 receptor that mediates internalization of the virus into renal tubular cells, from which the virus can be rescued and disseminated by encountering immune cells. PMID- 17287425 TI - Presentation of the Goodpasture autoantigen requires proteolytic unlocking steps that destroy prominent T cell epitopes. AB - The most abundant autoreactive T cells in patients with Goodpasture's disease are specific for peptides in the autoantigen that have high affinity for the disease associated HLA class II molecule, DR15. How can such T cells escape self tolerance mechanisms? This study showed that these peptides are highly susceptible to destruction in the earliest stages of antigen processing, and some must be cleaved for antigen digestion to be possible ("unlocking"). Goodpasture autoantigen [collagen alpha3(IV)NC1; approximately 31 kD] that was incubated with B cell lysosomes was cleaved within a few minutes to form approximately 9- and approximately 22-kD fragments, then increasing quantities of smaller peptides. The processing was completely abrogated by pepstatin A, a specific inhibitor of cathepsin D/E, even though lysosomal extracts contain a rich array of proteases. Purified cathepsin D generated the same major alpha3(IV)NC1 fragments as entire lysosomes, suggesting that cathepsin D cleavages are required to initiate alpha3(IV)NC1 processing. The initial unlocking cleavages destroyed two major self-epitopes, and subsequent preferred cleavages destroyed all of the other T cell epitopes that are recognized by most patients' autoreactive T cells. The responses of T cell clones that are specific for a major disease-associated peptide to antigen-pulsed intact antigen-presenting cells were substantially enhanced by pepstatin A treatment. Therefore, cathepsin D activity significantly diminishes presentation of alpha3(IV)NC1 peptides that are recognized by patients' T cells by destroying the peptides in early processing. These observations can explain why the mature T cell repertoire includes reactivity toward these self-peptides and suggests that a key factor in disease initiation is likely to be a shift in antigen processing. PMID- 17287426 TI - Insulin induces renal vasodilation, increases plasma renin activity, and sensitizes the renal vasculature to angiotensin receptor blockade in healthy subjects. AB - Insulin stimulates the renin-angiotensin system and induces renal vasodilation. The relationship between these opposing influences of insulin on renal vascular tone has not been explored. A hyperinsulinemic euglycemic clamp and sham insulin clamp each of 270 min duration were performed in 15 healthy individuals during high sodium balance. An angiotensin receptor blocker was administered at time 180 min. Renal plasma flow and plasma renin activity were measured serially. The response to insulin or sham insulin infusion was defined as the change from time 0 to 180 min; the response to angiotensin receptor blockade (ARB) was defined as the change from time 180 to 270 min. Insulin infusion increased plasma renin activity (P < 0.01) and renal plasma flow (P < 0.01); the latter effect plateaued by time 150 min. ARB caused a greater vasodilator response during insulin infusion compared with during sham insulin infusion (P = 0.02). Increasing renin response to insulin predicted blunting of the renal vasodilator response to insulin infusion (R(2) = 0.36, P = 0.02) and sensitizing of the renal vasodilator response to ARB during insulin infusion (R(2) = 0.59, P < 0.01). Insulin-induced activation of the renin-angiotensin system modulates insulin-induced renal vasodilation in healthy individuals. Further studies are warranted to address this balance in states of insulin resistance and the possible implications for the association of insulin resistance with risk for chronic kidney disease. PMID- 17287427 TI - Active focal segmental glomerulosclerosis is associated with massive oxidation of plasma albumin. AB - The basic mechanism for idiopathic FSGS still is obscure. Indirect evidence in humans and generation of FSGS by oxidants in experimental models suggest a role of free radicals. In vitro studies demonstrate a main role of plasma albumin as antioxidant, its modification representing a chemical marker of oxidative stress. With the use of complementary liquid chromatography electron spray ionization tandem mass spectrometry (LC-ESI-MS/MS) and biochemical methods, plasma albumin was characterized in 34 patients with FSGS; 18 had received a renal transplant, and 17 had IgM mesangial deposition. Patients with FSGS that was in remission or without recurrence after transplantation had normal plasma albumin, and the same occurred in patients with primary and secondary nephrites and with chronic renal failure. In contrast, patients with active FSGS or with posttransplantation recurrence had oxidized plasma albumin. This finding was based on the characterization of albumin Cys 34 with an mass-to-charge ratio of 511.71 in triple charge that was consistent with the formation of a cysteic acid carrying a sulfonic group (alb-SO(3)(-)). The exact mass of albumin was increased accordingly (+48 Da) for incorporation of three oxygen radicals. Direct titration of the free sulfhydryl group 34 of plasma albumin and electrophoretic titration curves confirmed loss of free sulfhydryl group and formation of a fast-moving isoform in all cases with disease activity. This is the first demonstration of in vivo plasma albumin oxidation that was obtained with an adequate structural approach. Albumin oxidation seems to be specific for FSGS, suggesting some pathogenetic implications. Free radical involvement in FSGS may lead to specific therapeutic interventions. PMID- 17287428 TI - Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in experimental glomerulonephritis in mice. AB - The role of thrombospondin 2 (TSP2) was investigated in an anti-glomerular basement membrane (GBM) nephritis model that compared TSP2-null mice with wild type (WT) controls. TSP2-null mice were analyzed for kidney function, renal cortical matrix expansion, influx of inflammatory cells, proliferation, and apoptosis, as well as for capillary rarefaction after induction of anti-GBM disease. Whereas the renal cortex of normal control WT mice did not show any detectable TSP2 staining above background, TSP2 protein expression was clearly upregulated in anti-GBM disease. TSP2 deficiency led to an accelerated and enhanced inflammatory response, as indicated by the influx of CD4(+) and CD8a(+) cells and monocytes/macrophages. Glomerular fibrin deposition and a matrix remodeling response were also observed, as indicated by collagens I and IV staining and a proliferative response within the renal interstitium. These changes were accompanied by increased matrix metalloproteinase 2 activity and enhanced alpha-smooth muscle actin staining in the TSP2-null mice. Neither a compensatory increase in TSP1 nor increased phosphorylation of Smad 2/3, an indicator for TGF-beta activity, was observed. The proliferative response of the peritubular endothelium was accelerated and enhanced, leading to a reversal of capillary rarefaction in TSP2-null mice, whereas interstitial cell death was equivalent to that in WT mice. In conclusion, the lack of the matricellular protein TSP2 in mice accelerates and enhances several responses to renal injury and reveals an important role for TSP2 as a major endogenous antiangiogenic and matrix metalloproteinase 2-regulating factor in renal disease. PMID- 17287429 TI - Distribution of alpha-galactosidase A in normal human kidney and renal accumulation and distribution of recombinant alpha-galactosidase A in Fabry mice. AB - Deficiency of lysosomal alpha-galactosidase A (alpha-Gal A) in Fabry disease results in cellular accumulation of globotriaosylceramide (Gl3), often leading to end-stage renal failure. Gl3 accumulates in endothelial, glomerular, and tubular cells. Replacement therapy with recombinant alpha-Gal A to some extent reduces cellular accumulation of Gl3 in the kidney. This study shows high lysosomal expression of alpha-Gal A in all tubular segments and interstitial cells of normal human kidney. However, glomeruli and endothelial cells did not express the enzyme to any significant extent. Recombinant enzyme was taken up by rat yolk sac cells in a receptor-associated protein-inhibitive manner, and surface plasmon resonance experiments revealed binding to megalin, indicating a possible mechanism for uptake of alpha-Gal A in the tubular cells. After infusion into experimental animals or patients, alpha-Gal A was recovered in the urine, indicating glomerular filtration. Recombinant alpha-Gal A was also found in kidneys of normal and alpha-Gal A knockout mice by Western blotting and localized to endosomes and lysosomes in proximal tubules, interstitial cells, and glomerular podocytes by immunocytochemistry and autoradiography but not in vascular endothelial cells. In conclusion, intravenously administered enzyme is taken up by interstitial cells, is to some extent filtered in glomeruli, and is taken up by podocytes and reabsorbed by receptor-mediated endocytosis in proximal tubule cells, directly indicating a potential beneficial effect of enzyme replacement therapy for these cells. PMID- 17287430 TI - Long-term, high-dosage candesartan suppresses inflammation and injury in chronic kidney disease: nonhemodynamic renal protection. AB - Recent evidence suggests that higher-than-usual antihypertensive dosages of renin angiotensin-aldosterone system blockers may provide additional protection from progression of chronic renal disease; however, there have been few long-term studies, and the underlying mechanisms remain uncertain. This study examined the effects of long-term (14 mo) administration of ultrahigh dosages of the angiotensin receptor blocker candesartan on the progression of renal injury in spontaneously hypertensive rats (SHR). Beginning 8 wk after birth, SHR underwent unilateral nephrectomy and were given vehicle (control), or candesartan at a standard 5 mg/kg per d (T5), high 25 mg/kg per d (T25), or ultrahigh 75 mg/kg per d dosage (T75). After 2 wk, BP was reduced in all treated groups; however, it was better controlled in the high-dosage groups (T25 and T75). Urinary protein was significantly reduced in T75 after 2 wk of treatment and was also declined in the other two treatment groups but only after 2 mo. Exogenous angiotensin II test showed that complete angiotensin receptor blockade was achieved only in the high dosage groups. Renal inflammation and macrophage (ED-1) infiltration were significantly ameliorated in both T25 and T75 but not in T5 rats. This was associated with the changes of tubular expression of monocyte chemoattractant protein-1, RANTES (regulated upon expression normal T cell expressed and secreted), and the phosphorylated NF-kappaB, a marker for activation. Suppression of ED-1, monocyte chemoattractant protein-1, and RANTES expression and NF-kappaB activation were greater in T75 as compared with T25. These findings suggest that candesartan has dosage-dependent, anti-inflammatory effects that are mediated by suppression of NF-kappaB activation and chemokine expression. Renal protection with high-dosage therapy may depend on these nonhemodynamic effects. PMID- 17287431 TI - Lack of endothelial nitric oxide synthase promotes endothelin-induced hypertension: lessons from endothelin-1 transgenic/endothelial nitric oxide synthase knockout mice. AB - Endothelin-1 (ET-1) is one of the most potent biologic vasoconstrictors. Nevertheless, transgenic mice that overexpress ET-1 exhibit normal BP. It was hypothesized that vascular effects of ET-1 may be antagonized by an increase of the endothelial counterpart of ET-1, nitric oxide (NO), which is produced by the endothelial NO synthase (eNOS). Therefore, cross-bred animals of ET transgenic mice (ET+/+) and eNOS knockout (eNOS-/-) mice and were generated, and BP and endothelial function were evaluated in these animals. Endothelium-dependent and independent vascular function was assessed as relaxation/contraction of isolated preconstricted aortic rings. The tissue ET and NO system was determined in aortic rings by quantitative real-time PCR and Western blotting. Systolic BP was similar in ET+/+ and wild-type (WT) mice but was significantly elevated in eNOS-/- mice (117 +/- 4 mmHg versus 94 +/- 6 mmHg in WT mice; P < 0.001) and even more elevated in ET+/+ eNOS-/- cross-bred mice (130 +/- 4 mmHg; P < 0.05 versus eNOS-/ ). Maximum endothelium-dependent relaxation was enhanced in ET+/+ mice (103 +/- 6 versus 87 +/- 4% of preconstriction in WT littermates; P < 0.05) and was completely blunted in eNOS-/- (-3 +/- 4%) and ET+/+ eNOS-/- mice (-4 +/- 4%), respectively. Endothelium-independent relaxation was comparable among all groups. Quantitative real-time PCR as well as Western blotting revealed an upregulation of the aortic ET(A) and ET(B) receptors in ET+/+ eNOS-/-, whereas eNOS was absent in aortic rings of eNOS-/- and ET+/+ eNOS-/- mice. ET-1 aortic tissue concentrations were similar in WT mice and ET+/+ eNOS-/- mice most probably as a result of an enhanced clearance of ET-1 by the upregulated ET(B) receptor. These data show for the first time that in transgenic mice that overexpress human ET-1, additional knockout of eNOS results in a further enhancement of BP as compared with eNOS-/- mice. The human ET+/+ eNOS-/- mice therefore represent a novel model of hypertension as a result of an imbalance between the vascular ET-1 and NO systems. PMID- 17287432 TI - Cystic fibrosis is associated with a defect in apical receptor-mediated endocytosis in mouse and human kidney. AB - Inactivation of the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) causes cystic fibrosis (CF). Although CFTR is expressed in the kidney, no overwhelming renal phenotype has been documented in patients with CF. This study investigated the expression, subcellular distribution, and processing of CFTR in the kidney; used various mouse models to assess the role of CFTR in proximal tubule (PT) endocytosis; and tested the relevance of these findings in patients with CF. The level of CFTR mRNA in mouse kidney approached that found in lung. CFTR was located in the apical area of PT cells, with a maximal intensity in the straight part (S3) of the PT. Fractionation showed that CFTR co distributed with the chloride/proton exchanger ClC-5 in PT endosomes. Cftr(-/-) mice showed impaired (125)I-beta(2)-microglobulin uptake, together with a decreased amount of the multiligand receptor cubilin in the S3 segment and a significant loss of cubilin and its low molecular weight (LMW) ligands into the urine. Defective receptor-mediated endocytosis was found less consistently in Cftr(DeltaF/DeltaF) mice, characterized by a large phenotypic heterogeneity and moderate versus mice that lacked ClC-5. A significant LMW proteinuria (and particularly transferrinuria) also was documented in a cohort of patients with CF but not in patients with asthma and chronic lung inflammation. In conclusion, CFTR inactivation leads to a moderate defect in receptor-mediated PT endocytosis, associated with a cubilin defect and a significant LMW proteinuria in mouse and human. The magnitude of the endocytosis defect that is caused by CFTR versus ClC 5 loss likely reflects functional heterogeneity along the PT. PMID- 17287433 TI - Multiple saccades are more automatic than single saccades. AB - In this paper, we demonstrate that when a peripheral object is foveated by a sequence of multiple saccades, the initial saccade in the sequence is initiated markedly faster than a single accurate saccade to the same object. We suggest that multiple saccades represent a more automatic form of oculomotor planning that may be the result of a reduced influence from the cerebral cortex. To test this, we compared single and multiple saccade characteristics across development. We find that in contrast to the reduction in the latency of single saccades that is observed across development, the latency of initial saccades in multiple saccade sequences is remarkably stable across all age groups. Moreover, the longer the latency of this initial saccade, the more accurate it is, suggesting that there is a relation between the degree of procrastination and the accuracy of the response. Finally, the frequency with which multiple saccades occurred within each age group was positively correlated with the tendency to generate erroneous saccades during a fixation control task. Taken together, the present data suggest that multiple saccades are generated in a more automatic manner than single saccades. PMID- 17287434 TI - Signaling mechanisms of angiotensin II-induced attenuation of GABAergic input to hypothalamic presympathetic neurons. AB - The hypothalamic paraventricular nucleus (PVN) is an important site for the regulation of sympathetic outflow. Angiotensin II (Ang II) can activate AT(1) receptors to stimulate PVN presympathetic neurons through inhibition of GABAergic input. However, little is known about the downstream pathway involved in this presynaptic action of Ang II in the PVN. In this study, using whole cell recording from retrogradely labeled PVN neurons in rat brain slices, we determined the signaling mechanisms responsible for the effect of Ang II on synaptic GABA release to spinally projecting PVN neurons. Bath application of Ang II reproducibly decreased the frequency of GABAergic miniature postsynaptic inhibitory currents (mIPSCs) in fluorescence-labeled PVN neurons. Ang II failed to change the frequency of mIPSCs in labeled PVN neurons treated with pertussis toxin. However, Ang II-induced inhibition of mIPSCs persisted in the presence of either CdCl(2), a voltage-gated Ca(2+) channel blocker, or 4-aminopyridine, a blocker of voltage-gated K(+) channels. Interestingly, inhibition of superoxide with superoxide dismutase or Mn(III) tetrakis (4-benzoic acid) prophyrin completely blocked Ang II-induced decrease in mIPSCs. By contrast, inhibition of hydroxyl radical formation with the ion chelator deferoxamine did not significantly alter the effect of Ang II. These findings suggest that the presynaptic action of Ang II on synaptic GABA release in the PVN is mediated by the pertussis toxin-sensitive G(i/o) proteins but not by voltage-gated Ca(2+) and K(+) channels. Ang II attenuates GABAergic input to PVN presympathetic neurons through reactive oxygen species, especially superoxide anions. PMID- 17287435 TI - Differential effects of opioids on sacrocaudal afferent pathways and central pattern generators in the neonatal rat spinal cord. AB - The effects of opioids on sacrocaudal afferent (SCA) pathways and the pattern generating circuitry of the thoracolumbar and sacrocaudal segments of the spinal cord were studied in isolated spinal cord and brain stem-spinal cord preparations of the neonatal rat. The locomotor and tail moving rhythm produced by activation of nociceptive and nonnociceptive sacrocaudal afferents was completely blocked by specific application of the mu-opioid receptor agonist [d-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin acetate salt (DAMGO) to the sacrocaudal but not the thoracolumbar segments of the spinal cord. The rhythmic activity could be restored after addition of the opioid receptor antagonist naloxone to the experimental chamber. The opioid block of the SCA-induced rhythm is not due to impaired rhythmogenic capacity of the spinal cord because a robust rhythmic activity could be initiated in the thoracolumbar and sacrocaudal segments in the presence of DAMGO, either by stimulation of the ventromedial medulla or by bath application of N-methyl-d-aspartate/serotonin. We suggest that the opioid block of the SCA-induced rhythm involves suppression of synaptic transmission through sacrocaudal interneurons interposed between SCA and the pattern-generating circuitry. The expression of mu opioid receptors in several groups of dorsal, intermediate and ventral horn interneurons in the sacrocaudal segments of the cord, documented in this study, provides an anatomical basis for this suggestion. PMID- 17287436 TI - Limits of linear rate coding of dynamic stimuli by electroreceptor afferents. AB - We estimated the frequency-intensity (f-I) curves of P-unit electroreceptors using 4-Hz random amplitude modulations (RAMs) and using the covariance method (50-Hz RAMs). Both methods showed that P units are linear encoders of stimulus amplitude with additive noise; the gain of the f-I curve was, on average, 0.32 and 2.38 spikesxs(-1)xmicroV(-1) for the low- and high-frequency cutoffs, respectively. There were two sources of apparent noise in the encoding process: the first was the variability of baseline P-unit discharge and the second was the variation of receptor discharge due to variability of the stimulus slope independent of its intensity. The covariance method showed that a linear combination of eigenvectors representing the time-weighted stimulus intensity (E1) and its derivative (E2) could account for, on average, 92% of the total response variability; E1 by itself accounted for 76% of the variability. The low gain of the low-frequency f-I curve implies that detection of small (1 microV) signals would require integration over many receptors ( approximately 1,200) and time (200 ms); even then, signals that elicit behavioral responses could not be detected using rate coding with the estimated gain and noise levels. Weak signals at the limit of behavioral thresholds could be detected if the animal were able to extract E1 from the population of responding P units; we propose a tentative mechanism for this operation although there is no evidence as to whether it is actually implemented in the nervous system of these fish. PMID- 17287438 TI - Control of hand impedance under static conditions and during reaching movement. AB - It is known that humans can modify the impedance of the musculoskeletal periphery, but the extent of this modification is uncertain. Previous studies on impedance control under static conditions indicate a limited ability to modify impedance, whereas studies of impedance control during reaching in unstable environments suggest a greater range of impedance modification. As a first step in accounting for this difference, we quantified the extent to which stiffness changes from posture to movement even when there are no destabilizing forces. Hand stiffness was estimated under static conditions and at the same position during both longitudinal (near to far) and lateral movements using a position servo technique. A new method was developed to predict the hand "reference" trajectory for purposes of estimating stiffness. For movements in a longitudinal direction, there was considerable counterclockwise rotation of the hand stiffness ellipse relative to stiffness under static conditions. In contrast, a small counterclockwise rotation was observed during lateral movement. In the modeling studies, even when we used the same modeled cocontraction level during posture and movement, we found that there was a substantial difference in the orientation of the stiffness ellipse, comparable with that observed empirically. Indeed, the main determinant of the orientation of the ellipse in our modeling studies was the movement direction and the muscle activation associated with movement. Changes in the cocontraction level and the balance of cocontraction had smaller effects. Thus even when there is no environmental instability, the orientation of stiffness ellipse changes during movement in a manner that varies with movement direction. PMID- 17287439 TI - Identification and dynamics of spontaneous burst initiation zones in unidimensional neuronal cultures. AB - Spontaneous activity is typical of in vitro neural networks, often in the form of large population bursts. The origins of this activity are attributed to intrinsically bursting neurons and to noisy backgrounds as well as to recurrent network connections. Spontaneous activity is often observed to emanate from localized sources or initiation zones, propagating from there to excite large populations of neurons. In this study, we use unidimensional cultures to overcome experimental difficulties in identifying initiation zones in vivo and in dissociated two-dimensional cultures. We found that spontaneous activity in these cultures is initiated exclusively in localized zones that are characterized by high neuronal density but also by recurrent and inhibitory network connections. We demonstrate that initiation zones compete in driving network activity in a winner-takes-most scenario. PMID- 17287440 TI - Functional regulation of T-type calcium channels by s-nitrosothiols in the rat thalamus. AB - Although T-type Ca(2+) channels in the reticular thalamic nucleus (nRT) have a central function in tuning neuronal excitability and are implicated in sensory processing, sleep, and epilepsy, the mechanisms involved in their regulation are poorly understood. Here we recorded T-type Ca(2+) currents from intact nRT neurons in brain slices from young rats and investigated the mechanisms of T-type channel modulation by S-nitrosothiols (SNOs). We found that extracellular application of S-nitrosoglutathione (GSNO), S-nitrosocysteine (CSNO) and S nitroso-N-acetyl-penicillamin (SNAP) rapidly and reversibly reduced T-type currents. The effects of SNOs are strongly stereoselective at physiological concentrations: (L)-CSNO was fourfold more effective in inhibiting T-type current than was (D)-CSNO. The effects of GSNO were abolished if cells had been treated with free hemoglobin or N-ethylmaleimide, an irreversible alkylating agent but not by 8-bromoguanosine-3',5'-cyclomonophosphate sodium salt, a membrane-permeant cGMP analogue or 1H-(1,2,4) oxadiazolo (4,3-a) quinoxalin-1-one, a specific soluble guanylyl cyclase inhibitor. In addition, bath applications of GSNO inhibited T-type currents in nucleated outside-out patches and whole cell recordings to a similar extent, with minimal effect on cell-attached recordings, suggesting a direct effect of GSNO on putative extracellular thiol residues on T type channels. Biophysical studies indicate that GSNO decreased the availability of T-type channels at physiological potentials by modifying gating and stabilizing inactive states of the channels. In current-clamp experiments, GSNO diminished the amplitude of low-threshold calcium spikes and frequency of spike firing with minimal effects on the passive membrane properties. Collectively, the results indicate that SNOs may be a class of endogenous agents that control the functional states of the thalamus. PMID- 17287437 TI - Beta rhythms (15-20 Hz) generated by nonreciprocal communication in hippocampus. AB - Generation of gamma rhythms in reciprocally connected areas of cortex produces synchronous neuronal firing, although little is known about the consequences of gamma rhythms when generated in nonreciprocally connected regions. This nonreciprocity exists in hippocampus, where gamma rhythms are generated in area CA3 in vitro and in vivo and nonreciprocally projected to area CA1 by the Schaffer collateral pathway. Here we demonstrate how this CA3 gamma rhythm generates two different patterns of local CA1 oscillation dependent on the degree of output from area CA1. 1) In conditions where activity projected to area CA1 produces only very low principal cell recruitment the local population rhythm mimics the gamma rhythm projected from CA3. This activity is generated predominantly by recruitment of CA1 basket cells in a manner dependent on phasic, feedforward excitation of this interneuron subclass. Interneurons in stratum oriens, not receiving CA3 feedforward input, fired at theta frequencies. 2) In the presence of serotonin CA1 principal cell recruitment was appreciably enhanced, resulting in dual activation of CA1 basket cells through both feedforward and feedback excitations. Feedback excitation to CA1 stratum oriens interneurons was also enhanced. The resulting change in interneuron network dynamics generated a beta-frequency CA1 rhythm (as a near-subharmonic of the gamma rhythm projected from CA3). These findings demonstrate that in nonreciprocally connected networks, the frequency of population rhythms in target areas serves to code for degree of principal cell recruitment by afferent input. PMID- 17287441 TI - Heat sensitization in skin and muscle nociceptors expressing distinct combinations of TRPV1 and TRPV2 protein. AB - Recordings were made from small and medium diameter dorsal root ganglia (DRG) neurons that expressed transient receptor potential (TRP) proteins. Physiologically characterized skin nociceptors expressed either TRPV1 (type 2) or TRPV2 (type 4) in isolation. Other nociceptors co-expressed both TRP proteins and innervated deep tissue sites (gastrocnemius muscle, distal colon; type 5, type 8) and skin (type 8). Subpopulations of myelinated (type 8) and unmyelinated (type 5) nociceptors co-expressed both TRPs. Cells that expressed TRPV1 were excellent transducers of intense heat. Proportional inward currents were obtained from a threshold of approximately 46.5 to approximately 56 degrees C. In contrast, cells expressing TRPV2 alone (52 degrees C threshold) did not reliably transduce the intensity of thermal events. Studies were undertaken to assess the capacity of skin and deep nociceptors to exhibit sensitization to repeated intense thermal stimuli [heat-heat sensitization (HHS)]. Only nociceptors that expressed TRPV2, alone or in combination with TRPV1, exhibited HHS. HHS was shown to be Ca(2+) dependent in either case. Intracellular Ca(2+) dependent pathways to HHS varied with the pattern of TRP protein expression. Cells co-expressing both TRPs modulated heat reactivity through serine/threonine phosphorylation or PLA(2) dependent pathways. Cells expressing only TRPV2 may have relied on tyrosine kinases for HHS. We conclude that heat sensitization in deep and superficial capsaicin and capsaicin-insensitive C and Adelta nociceptors varies with the distribution of TRPV1 and TRPV2 proteins. The expression pattern of these proteins are specific to subclasses of physiologically identified C and A fiber nociceptors with highly restricted tissue targets. PMID- 17287442 TI - Noncommutative updating of perceived self-orientation in three dimensions. AB - After whole body rotations around an earth-vertical axis in darkness, subjects can indicate their orientation in space with respect to their initial orientation reasonably well. This is possible because the brain is able to mathematically integrate self-velocity information provided by the vestibular system to obtain self-orientation, a process called path integration. For rotations around multiple axes, however, computations are more demanding to accurately update self orientation with respect to space. In such a case, simple integration is no longer sufficient because of the noncommutativity of rotations. We investigated whether such updating is possible after three-dimensional whole body rotations and whether the noncommutativity of three-dimensional rotations is taken into account. The ability of ten subjects to indicate their spatial orientation in the earth-horizontal plane was tested after different rotational paths from upright to supine positions. Initial and final orientations of the subjects were the same in all cases, but the paths taken were different, and so were the angular velocities sensed by the vestibular system. The results show that seven of the ten subjects could consistently indicate their final orientation within the earth horizontal plane. Thus perceived final orientation was independent of the path taken, i.e., the noncommutativity of rotations was taken into account. PMID- 17287443 TI - Roles of ionic currents in lamprey CpG neurons: a modeling study. AB - The spinal network underlying locomotion in the lamprey consists of a core network of glutamatergic and glycinergic interneurons, previously studied experimentally and through mathematical modeling. We present a new and more detailed computational model of lamprey locomotor network neurons, based primarily on detailed electrophysiological measurements and incorporating new experimental findings. The model uses a Hodgkin-Huxley-like formalism and consists of 86 membrane compartments containing 12 types of ion currents. One of the goals was to introduce a fast, transient potassium current (K(t)) and two sodium-dependent potassium currents, one faster (K(NaF)) and one slower (K(NaS)), in the model. Not only has the model lent support to the interpretation of experimental results but it has also provided predictions for further experimental analysis of single-network neurons. For example, K(t) was shown to be one critical factor for controlling action potential duration. In addition, the model has proved helpful in investigating the possible influence of the slow afterhyperpolarization on repetitive firing during ongoing activation. In particular, the balance between the simulated slow sodium-dependent and calcium dependent potassium currents has been explored, as well as the possible involvement of dendritic conductances. PMID- 17287445 TI - Visual and auditory alertness: modality-specific and supramodal neural mechanisms and their modulation by nicotine. AB - Alertness is a nonselective attention component that refers to a state of general readiness that improves stimulus processing and response initiation. We used functional magnetic resonance imaging (fMRI) to identify neural correlates of visual and auditory alertness. A further aim was to investigate the modulatory effects of the cholinergic agonist nicotine. Nonsmoking participants were given either placebo or nicotine (NICORETTE gum, 2 mg) and performed a target-detection task with warned and unwarned trials in the visual and auditory modality. Our results provide evidence for modality-specific correlates of visual and auditory alertness in respective higher-level sensory cortices and in posterior parietal and frontal brain areas. The only region commonly involved in visual and auditory alertness was the right superior temporal gyrus. A connectivity analysis showed that this supramodal region exhibited modality-dependent coupling with respective higher sensory cortices. Nicotine was found to mainly decrease visual and auditory alertness-related activity in several brain regions, which was evident as a significant interaction of nicotine-induced decreases in BOLD signal in warned trials and increases in unwarned trials. The cholinergic drug also affected alerting-dependent activity in the supramodal right superior temporal gyrus; here the effect was the result of a significant increase of neural activity in unwarned trials. We conclude that the role of the right superior temporal gyrus is to induce an "alert" state in response to warning cues and thereby optimize stimulus processing and responding. We speculate that nicotine increases brain mechanisms of alertness specifically in conditions where no extrinsic warning is provided. PMID- 17287444 TI - Motor strategies used by rats spinalized at birth to maintain stance in response to imposed perturbations. AB - Some rats spinalized P1/P2 achieve autonomous weight-supported locomotion and quiet stance as adults. We used force platforms and robot-applied perturbations to test such spinalized rats (n = 6) that exhibited both weight-supporting locomotion and stance, and also normal rats (n = 8). Ground reaction forces in individual limbs and the animals' center of pressure were examined. In normal rats, both forelimbs and hindlimbs participated actively to control horizontal components of ground reaction forces. Rostral perturbations increased forelimb ground reaction forces and caudal perturbations increased hindlimb ground reaction forces. Operate rats carried 60% body weight on the forelimbs and had a more rostral center of pressure placement. The pattern in normal rats was to carry significantly more weight on the hindlimbs in quiet stance (roughly 60%). The strategy of operate rats to compensate for perturbations was entirely in forelimbs; as a result, the hindlimbs were largely isolated from the perturbation. Stiffness magnitude of the whole body was measured: its magnitude was hourglass shaped, with the principal axis oriented rostrocaudally. Operate rats were significantly less stiff--only 60-75% of normal rats' stiffness. The injured rats adopt a stance strategy that isolates the hindlimbs from perturbation and may thus prevent hindlimb loadings. Such loadings could initiate reflex stepping, which we observed. This might activate lumbar pattern generators used in their locomotion. Adult spinalized rats never achieve independent hindlimb weight-supported stance. The stance strategy of the P1 spinalized rats differed strongly from the behavior of intact rats and may be difficult for rats spinalized as adults to master. PMID- 17287446 TI - Facilitating sensory responses in developing mouse somatosensory barrel cortex. AB - The sensory responses in the barrel cortex of mice aged postnatal day (P)7-P12 evoked by a single whisker deflection are smaller in amplitude and spread over a smaller area than those measured in P13-P21 mice. However, repetitive 10-Hz stimulation or paired pulse whisker stimulation in P7-P12 mice evoked facilitating sensory responses, contrasting with the depressing sensory responses observed in P13-P21 mice. This facilitation occurred during an interval ranging 300-1,000 ms after the first stimulus and was measured using whole cell recordings, voltage-sensitive dye imaging, and calcium-sensitive dye imaging. The facilitated responses were not only larger in amplitude but also propagated over a larger cortical area. The facilitation could be blocked by local application of pharmacological agents reducing cortical excitability. Local cortical microstimulation could substitute for the first whisker stimulus to produce a facilitated sensory response. The enhanced sensory responses evoked by repetitive sensory stimuli in P7-P12 mice may contribute to the activity-dependent specification of the developing cortical circuits. In addition, the facilitating sensory responses allow long integration times for sensory processing compatible with the slow behavior of mice during early postnatal development. PMID- 17287447 TI - The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. AB - BACKGROUND: Factors that may obscure the diagnosis of varicella zoster virus (VZV) vasculopathy include the absence of rash before TIAs or stroke as well as similar clinical features and imaging, angiographic, and CSF abnormalities to those of other vasculopathies. Diagnosis relies on virologic confirmation that detects VZV DNA, anti-VZV IgG antibody, or both in the CSF. METHODS: We reviewed our current 14 cases of patients diagnosed with VZV vasculopathy based on combined clinical, imaging, angiographic, or CSF abnormalities. All CSFs must have been tested for VZV DNA by PCR and for anti-VZV IgG antibody by enzyme immunoassay and found to be positive for either or both. Of the 14 subjects, 8 had a history of recent zoster, whereas 6 had no history of zoster rash before developing vasculopathy. RESULTS: All 14 subjects (100%) had anti-VZV IgG antibody in their CSF, whereas only 4 (28%) had VZV DNA. The detection of anti VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). CONCLUSIONS: In varicella zoster virus (VZV) vasculopathy, the diagnostic value of detecting anti-VZV IgG antibody in CSF is greater than that of detecting VZV DNA. Although a positive PCR for VZV DNA in CSF is helpful, a negative PCR does not exclude the diagnosis of VZV vasculopathy. Only when the CSF is negative for both VZV DNA and anti-VZV IgG antibody can the diagnosis of VZV vasculopathy be excluded. PMID- 17287448 TI - Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. AB - OBJECTIVE: To investigate the neurocognitive measures that best predict progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD). METHODS: We evaluated 539 participants with aMCI from the Alzheimer's Disease Cooperative Study clinical drug trial of donepezil, vitamin E, or placebo. During the study period of 36 months, 212 aMCI participants progressed to AD. Using progression from aMCI to AD within 36 months as the dependent variable, a generalized linear model was fit to the data using the least absolute shrinkage and selection operator. Independent variables included in this analysis were age, sex, education, APOE-e4 (APOE4) status, family history of dementia, Mini-Mental State Examination score, Digits Backwards (Wechsler Memory Scale), Maze Time and Errors, Number Cancellation, Delayed Recall of Alzheimer's Disease Assessment Scale Word List, New York University Paragraph Recall Test (Immediate and Delayed), Boston Naming Test, Category Fluency, Clock Drawing Test, and the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog). RESULTS: The model that best predicted progression from aMCI to AD over 36 months included APOE4 status, the Symbol Digit Modalities Test, Delayed 10-Word List Recall, New York University Paragraph Recall Test (Delayed), and the ADAS-cog total score. When APOE4 was removed from the analysis the resulting model had a similar estimated predictive accuracy as the full model. As determined by cross validation, the estimated predictive accuracy of the final model was 80%. CONCLUSION: Progression from amnestic mild cognitive impairment to Alzheimer disease in this cohort was best determined by combining four common, easily administered, cognitive measures. PMID- 17287449 TI - NMO-IgG in the diagnosis of neuromyelitis optica. PMID- 17287450 TI - Symptomatic dysferlin gene mutation carriers: characterization of two cases. AB - OBJECTIVE: To describe two symptomatic dysferlin gene mutation carriers. METHODS: One patient had limb girdle weakness. His brother was diagnosed with limb girdle muscular dystrophy 2B with two mutations in the dysferlin gene (D625Y and E1734G). The second patient had distal weakness. He had two sons with Miyoshi myopathy with a homozygous mutation (G519R). We performed immunofluorescence (dystrophin, DAG proteins, dysferlin, caveolin-3), Western blot (dysferlin, caveolin-3, calpain-3), and real-time PCR (dysferlin) using skeletal muscle samples. We also studied dysferlin in peripheral blood monocytes (PBMs) by Western blot. RESULTS: In addition to the muscle weakness, both patients showed elevated creatine kinase and abnormal muscle MRI. They presented a mutation in only one allele after screening of the whole gene (skeletal muscle and monocyte mRNA and genomic DNA). A muscle biopsy specimen showed moderate dystrophic changes and patchy dysferlin expression in the sarcolemma. Western blot of both PBMs and skeletal muscle demonstrated a significant reduction in dysferlin. All the other proteins including caveolin-3 and calpain-3 were normal. Real-time PCR showed normal levels of dysferlin mRNA vs the patients' affected relatives. CONCLUSIONS: The diagnosis of symptomatic carriers of dysferlin mutations should be considered when a pathologic pattern of dysferlin protein is observed. PMID- 17287451 TI - Downmodulation of mitochondrial F0F1 ATP synthase by diazoxide in cardiac myoblasts: a dual effect of the drug. AB - Similar to ischemic preconditioning, diazoxide was documented to elicit beneficial bioenergetic consequences linked to cardioprotection. Inhibition of ATPase activity of mitochondrial F(0)F(1) ATP synthase may have a role in such effect and may involve the natural inhibitor protein IF(1). We recently documented, using purified enzyme and isolated mitochondrial membranes from beef heart, that diazoxide interacts with the F(1) sector of F(0)F(1) ATP synthase by promoting IF(1) binding and reversibly inhibiting ATP hydrolysis. Here we investigated the effects of diazoxide on the enzyme in cultured myoblasts. Specifically, embryonic heart-derived H9c2 cells were exposed to diazoxide and mitochondrial ATPase was assayed in conditions maintaining steady-state IF(1) binding (basal ATPase activity) or detaching bound IF(1) at alkaline pH. Mitochondrial transmembrane potential and uncoupling were also investigated, as well as ATP synthesis flux and ATP content. Diazoxide at a cardioprotective concentration (40 muM cell-associated concentration) transiently downmodulated basal ATPase activity, concomitant with mild mitochondria uncoupling and depolarization, without affecting ATP synthesis and ATP content. Alkaline stripping of IF(1) from F(0)F(1) ATP synthase was less in diazoxide-treated than in untreated cells. Pretreatment with glibenclamide prevented, together with mitochondria depolarization, inhibition of ATPase activity under basal but not under IF(1)-stripping conditions, indicating that diazoxide alters alkaline IF(1) release. Diazoxide inhibition of ATPase activity in IF(1)-stripping conditions was observed even when mitochondrial transmembrane potential was reduced by FCCP. The results suggest that diazoxide in a model of normoxic intact cells directly promotes binding of inhibitor protein IF(1) to F(0)F(1) ATP synthase and enhances IF(1) binding indirectly by mildly uncoupling and depolarizing mitochondria. PMID- 17287452 TI - Noninvasive assessment of left ventricular and myocardial contractility in middle aged men and women: disparate evolution above the age of 50? AB - End-systolic elastance (E(es)) is a frequently used index of left ventricular (LV) contractility. However, because of its inherent dependence on LV geometry, E(es) cannot be used to compare myocardial contractile state between ventricles with different geometries, which is the case in any cross-sectional study. Various normalization methods for E(es) have been proposed in the literature, but a standardized method is still lacking. In this study, we introduced a novel alternative normalization technique and compared it with three previously suggested methods. We tested all normalization methods to assess the age- and sex related differences in myocardial contractility in a large population sample of 2,184 middle-aged (ages, 35-55 yr) untreated subjects free from overt cardiovascular disease. Ventricular contractility E(es) was determined using a previously validated noninvasive single-beat method, based on two-dimensional echocardiographic and brachial blood pressure measurements. Myocardial contractility was estimated as 1) E(es).end-diastolic volume (EDV); 2) E(es).LV mass (LVM); 3) 0.433.E(es).LVM/relative wall thickness (RWT), based on a theoretical LV model; and 4) 0.0941.E(es).LVM(0.455).RWT(-0.159), a novel semiempirical expression derived in this study. Because of the difference in their underlying assumptions, the various myocardial contractility indexes do not provide consistent information with respect to sex differences. Despite these discrepancies, it was found that myocardial contractility in women appears to be better preserved after the age of 50 yr compared with that in men. The physiological mechanisms behind this potentially clinically important phenomenon at population level require further investigation. PMID- 17287453 TI - Altered autonomic control in conscious transgenic rabbits with overexpressed cardiac Gsalpha. AB - Both enhanced sympathetic drive and altered autonomic control are involved in the pathogenesis of heart failure. The goal of the present study was to determine the extent to which chronically enhanced sympathetic drive, in the absence of heart failure, alters reflex autonomic control in conscious, transgenic (TG) rabbits with overexpressed cardiac Gsalpha. Nine TG rabbits and seven wild-type (WT) littermates were instrumented with a left ventricular (LV) pressure micromanometer and arterial catheters and studied in the conscious state. Compared with WT rabbits, LV function was enhanced in TG rabbits, as reflected by increased levels of LV dP/dt (5,600 +/- 413 vs. 3,933 +/- 161 mmHg/s). Baseline heart rate was also higher (P < 0.05) in conscious TG (247 +/- 10 beats/min) than in WT (207 +/- 10 beats/min) rabbits and was higher in TG after muscarinic blockade (281 +/- 9 vs. 259 +/- 8 beats/min) or combined beta-adrenergic receptor and muscarinic blockade (251 +/- 6 vs. 225 +/- 9 beats/min). Bradycardia was blunted (P < 0.05), whether induced by intravenous phenylephrine (arterial baroreflex), by cigarette smoke inhalation (nasopharyngeal reflex), or by veratrine administration (Bezold-Jarisch reflex). With veratrine administration, the bradycardia was enhanced in TG for any given decrease in arterial pressure. Thus the chronically enhanced sympathetic drive in TG rabbits with overexpressed cardiac Gsalpha resulted in enhanced LV function and heart rate and impaired reflex autonomic control. The impaired reflex control was generalized, not only affecting the high-pressure arterial baroreflex but also the low-pressure Bezold Jarisch reflex and the nasopharyngeal reflex. PMID- 17287454 TI - Simultaneous observation of DNA fragmentation and protein loss in the boar spermatozoon following application of the sperm chromatin dispersion (SCD) test. AB - DNA fragmentation and the nuclear protein matrix in boar spermatozoa were simultaneously assessed using a specific variant of the sperm chromatin dispersion (SCD) test that allows direct visualization of DNA and nuclear proteins under standard conditions of chemical lysis. Nuclear proteins remaining after lysis were stained with the fluorochrome 2,7-dibrom-4-hydroxy-mercury fluorescein for specific protein staining. DNA and nuclear protein were stained in control-untreated (no lysis) and treated sperm cells (lysis), resulting in the identification of 3 cell types: type 1: nonlysed (control-untreated) cells; type 2: lysed cells showing nonfragmented DNA; and type 3: lysed cells showing fragmented DNA. DNA damage was also purposely induced by incubating the sperm in 0.015% H(2)O(2) for 48 hours at 37 degrees C; the cells were correspondingly stained for DNA fragmentation and protein. Nonlysed control sperm (type 1) nuclei showed no halos and stained strongly for protein in the postacrosomal region. Lysed spermatozoa with nonfragmented DNA (type 2) showed evidence of restricted DNA loop dispersions at the caudal extremity of the sperm head and a more homogenous but similar distribution of protein matrix in comparison with untreated spermatozoa. Lysed spermatozoa with fragmented DNA (type 3) exhibited large halos of DNA loops and a loss of the nuclear protein matrix component. Sperm cells exposed to 48 hours' incubation at 37 degrees C and then treated with the lysing agent showed a concurrent and progressive loss of nuclear protein in association with correspondingly increased levels of DNA fragmentation. Discriminant analysis of quantitative fluorescence using digital image analysis and conducted after SCD processing revealed that DNA fragmentation and protein could be evaluated in an automated system. Ninety-seven percent of the total analyzed cells were accurately classified according to previously defined cell types (1, 2, and 3). The results of the current study demonstrated a synergistic relationship between that of nuclear protein alteration and DNA damage in the boar sperm cell. The importance of abnormal nuclear protein alteration to DNA fragmentation and any related effect on fertility remains to be investigated. PMID- 17287455 TI - Sperm DNA integrity from sperm to egg. PMID- 17287457 TI - Epigenetics in male germ cells. PMID- 17287456 TI - Late hormonal levels, semen parameters, and presence of antisperm antibodies in patients treated for testicular torsion. AB - In spite of prompt diagnosis and either orchiectomy or preservation of the affected testis, infertility remains a significant sequel to testicular torsion. The objective of this study was to evaluate the late endocrine profile, seminal parameters, and antisperm antibody levels after testicular torsion. We also analyzed the impact of orchiectomy or detorsion on the organ fate. Of 24 patients evaluated after testicular torsion, 15 were treated with orchiectomy (group 1) and 9 were treated with orchiopexy (group 2). All subjects were assessed by semen analysis, endocrine profile (levels of follicle-stimulating hormone, luteinizing hormone, and testosterone), and seminal antisperm antibody levels. A group of 20 proven fertile men was used as the control. Median ischemia time in group 1 (48 hours) was significantly higher than in group 2 (7 hours). Both groups demonstrated decreases in sperm count and morphology compared with controls. Group 1 showed a significantly higher motility than group 2 (P = .02). Group 1 also showed a significantly better morphology by World Health Organization and Kruger criteria than group 2 (P = .01). All patients presented endocrine profiles within the normal range, and no significant differences in antisperm antibody levels were detected between the groups. However, a trend for higher levels was found in patients treated for testicular torsion, regardless of the fate of the testis. Moreover, no significant correlation was found between antisperm antibody levels and age at torsion, ischemia time, seminal parameters, or treatment applied. In conclusion, we found that after torsion patients maintain late hormonal levels within the normal range. Testicular fate did not have any correlation with the formation of antisperm antibodies. Although sperm quality was preserved in most of the patients with the exception of sperm morphology, patients treated with orchiectomy presented better motility and morphology compared with the detorsion group. Further studies may clarify whether maintenance of a severely ischemic testicle may impair testicular function. PMID- 17287458 TI - Seminal plasma cobalamin significantly correlates with sperm concentration in men undergoing IVF or ICSI procedures. AB - Mild hyperhomocysteinemia is caused by B vitamin deficiencies. We hypothesize that these biochemical derangements detrimentally affect spermatogenesis. Therefore, the aim of this study was to investigate the folate, cobalamin, pyridoxine, and homocysteine concentrations in blood and seminal plasma and the associations between these biomarkers and semen parameters in men participating in an in vitro fertilization or intracytoplasmic sperm injection program. From 73 men (median age [range]: 37 years [28-53]), blood and semen samples were obtained for the determination of serum and red blood cell (RBC) folate, serum total cobalamin, whole-blood pyridoxal-5'-phosphate, plasma total homocysteine (tHcy), and serum total testosterone. Semen analysis included sperm concentration, motility, and morphology according to World Health Organization criteria. The B vitamins and tHcy concentrations were significantly correlated in blood but not in seminal plasma. The serum and RBC folate concentrations were significantly correlated also with the total folate concentration in seminal plasma (r = .44; P < .001 and r = .39; P < .001, respectively). Likewise, the total cobalamin concentration in serum and seminal plasma was significantly correlated (r = .55; P = .001). Of interest is that the total cobalamin concentration in seminal plasma was significantly correlated with the sperm concentration (r = .42; P < .001). This is in contrast to the absence of significant associations between the other vitamins and tHcy in blood and seminal plasma and any of the semen parameters. These findings suggest that folate and cobalamin are transferred from the blood to the male reproductive organs and emphasize the role of cobalamin in spermatogenesis in human. PMID- 17287459 TI - Biphasic effects of postnatal exposure to diethylhexylphthalate on the timing of puberty in male rats. AB - Phthalate esters such as di(2-ethylhexyl)phthalate (DEHP), which are commonly found in cosmetics and in flexible plastics distributed by the food, construction, and medical products industries, have been classified as anti androgens. High-dose DEHP exposure in utero is associated with decreased androgen levels. However, when administered after birth, low doses of DEHP (eg, 10 mg/kg body weight) may stimulate androgen production. In the present study, the potential of phthalate exposure to advance or delay the timing of puberty was assessed. Male Long-Evans rat pups were chronically subjected to low or high doses of DEHP, with the androgen-driven process of preputial separation serving as an index of pubertal timing. Rats were treated with 0, 10, 500, or 750 mg/kg body weight DEHP for 28 days starting at day 21 postpartum. The average age at which the animals completed preputial separation was measured in each group. The age of preputial separation was 41.5 +/- 0.1 days postpartum in controls (vehicle). The 10 mg/kg DEHP dose advanced pubertal onset significantly to 39.7 +/- 0.1 days postpartum, whereas the 750 mg/kg DEHP dose delayed pubertal onset to 46.3 +/- 0.1 days postpartum. The 10 mg/kg DEHP dose also significantly increased serum testosterone (T) levels (3.13 +/- 0.37 ng/mL) and seminal vesicle weights (0.33 +/- 0.02 g) compared with control serum T (1.98 +/- 0.20 ng/mL) and seminal vesicle weight (0.26 +/- 0.02 g), while the 750 mg/kg dose decreased serum T (1.18 +/- 0.18 ng/mL) as well as testes and body weights. Direct action of the DEHP metabolite, monoethylhexylphthalate (MEHP), on Leydig cell steroidogenic capacity was investigated in vitro. MEHP treatment at a low concentration (100 microM) increased luteinizing hormone-stimulated T production, whereas 10 mM concentrations were inhibitory. In conclusion, data from the present study indicate that DEHP has a biphasic effect on Leydig cell function, with low-dose exposure advancing the onset of puberty. High doses of DEHP, which are anti-androgenic, may also be outside the range of real environmental exposure levels. PMID- 17287461 TI - Novel insights into the regulation of the bound and diffusible glucokinase in MIN6 beta-cells. AB - A stable MIN6 beta-cell clone overexpressing glucokinase as an enhanced cyan fluorescent protein (ECFP) fusion construct was generated for analysis of glucokinase regulation in these glucose-responsive insulin-secreting cells. A higher glucokinase enzyme activity accompanied by an improved glucose-induced insulin secretion indicated the integration of ECFP-glucokinase into the functional pool of glucokinase protein in MIN6-ECFP-glucokinase cells. Fluorescence recovery after photobleaching experiments of MIN6-ECFP-glucokinase cells and photoactivation of a transiently transfected photoswitchable cyan fluorescent protein (PS-CFP)-glucokinase construct in MIN6 cells indicate a higher motility of the diffusible glucokinase fraction at high glucose concentrations. In agreement with previous studies, we observed significant binding of ECFP-glucokinase to insulin secretory granules. Using fluorescence lifetime imaging, we obtained evidence for an association between glucokinase and alpha-tubulin in MIN6-ECFP-glucokinase cells. Furthermore, immunohistochemistry and fluorescence resonance energy transfer analysis by acceptor photobleaching showed distinct association between endogenous glucokinase and alpha-tubulin as well as beta-tubulin in MIN6 cells. Interestingly, glucokinase was also colocalized with kinesin, a motor protein involved in insulin secretory granule movement. Therefore, we suggest a role of a bound glucokinase protein fraction in the regulation of insulin granule movement along tubulin filaments. PMID- 17287460 TI - Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity. AB - A growing body of evidence implicates ceramide and/or its glycosphingolipid metabolites in the pathogenesis of insulin resistance. We have developed a highly specific small molecule inhibitor of glucosylceramide synthase, an enzyme that catalyzes a necessary step in the conversion of ceramide to glycosphingolipids. In cultured 3T3-L1 adipocytes, the iminosugar derivative N-(5'-adamantane-1'-yl methoxy)-pentyl-1-deoxynojirimycin (AMP-DNM) counteracted tumor necrosis factor alpha-induced abnormalities in glycosphingolipid concentrations and concomitantly reversed abnormalities in insulin signal transduction. When administered to mice and rats, AMP-DNM significantly reduced glycosphingolipid but not ceramide concentrations in various tissues. Treatment of ob/ob mice with AMP-DNM normalized their elevated tissue glucosylceramide levels, markedly lowered circulating glucose levels, improved oral glucose tolerance, reduced A1C, and improved insulin sensitivity in muscle and liver. Similarly beneficial metabolic effects were seen in high fat-fed mice and ZDF rats. These findings provide further evidence that glycosphingolipid metabolites of ceramide may be involved in mediating the link between obesity and insulin resistance and that interference with glycosphingolipid biosynthesis might present a novel approach to the therapy of states of impaired insulin action such as type 2 diabetes. PMID- 17287462 TI - Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients. AB - Insulin resistance is the best predictor for the development of diabetes in offspring of type 2 diabetic patients, but the mechanism responsible for it remains unknown. Recent studies have demonstrated increased intramyocellular lipid, decreased mitochondrial ATP synthesis, and decreased mitochondrial density in the muscle of lean, insulin-resistant offspring of type 2 diabetic patients. These data suggest an important role for mitochondrial dysfunction in the pathogenesis of type 2 diabetes. To further explore this hypothesis, we assessed rates of substrate oxidation in the muscle of these same individuals using (13)C magnetic resonance spectroscopy (MRS). Young, lean, insulin-resistant offspring of type 2 diabetic patients and insulin-sensitive control subjects underwent (13)C MRS studies to noninvasively assess rates of substrate oxidation in muscle by monitoring the incorporation of (13)C label into C(4) glutamate during a [2 (13)C]acetate infusion. Using this approach, we found that rates of muscle mitochondrial substrate oxidation were decreased by 30% in lean, insulin resistant offspring (59.8 +/- 5.1 nmol x g(-1) x min(-1), P = 0.02) compared with insulin-sensitive control subjects (96.1 +/- 16.3 nmol x g(-1) x min(-1)). These data support the hypothesis that insulin resistance in skeletal muscle of insulin resistant offspring is associated with dysregulation of intramyocellular fatty acid metabolism, possibly because of an inherited defect in the activity of mitochondrial oxidative phosphorylation. PMID- 17287463 TI - Cell-permeable pentapeptide V5 inhibits apoptosis and enhances insulin secretion, allowing experimental single-donor islet transplantation in mice. AB - OBJECTIVE: Treatment of diabetic patients by pancreatic islet transplantation often requires the use of islets from two to four donors to produce insulin independence in a single recipient. Following isolation and transplantation, islets are susceptible to apoptosis, which limits their function and probably long-term islet graft survival. RESEARCH DESIGN AND METHODS: To address this issue, we examined the effect of the cell-permeable apoptosis inhibitor pentapeptide Val-Pro-Met-Leu-Lys, V5, on pancreatic islets in a mouse model. RESULTS: V5 treatment upregulated expression of anti-apoptotic proteins Bcl-2 and XIAP (X-linked inhibitor of apoptosis protein) by more than 3- and 11-fold and downregulated expression of apoptosis-inducing proteins Bax, Bad, and nuclear factor-kappaB-p65 by 10, 30, and nearly 50%, respectively. Treatment improved the recovered islet mass following collagenase digestion and isolation by 44% and in vitro glucose-responsive insulin secretion nearly fourfold. Following transplantation in streptozotocin-induced diabetic mice, 150 V5-treated islet equivalents functioned as well as 450 control untreated islet equivalents in normalizing blood glucose. CONCLUSIONS: These studies indicate that inhibition of apoptosis by V5 significantly improves islet function following isolation and improves islet graft function following transplantation. Use of this reagent in clinical islet transplantation could have a dramatic impact on the number of patients that might benefit from this therapy and could affect long-term graft survival. PMID- 17287465 TI - Characterization of donor dendritic cells and enhancement of dendritic cell efflux with CC-chemokine ligand 21: a novel strategy to prolong islet allograft survival. AB - Dendritic cells (DCs) are the most potent antigen-presenting cells, yet little data are available on the differential characteristics of donor and recipient DCs (dDCs and rDCs, respectively) during the process of islet allograft rejection. DTR-GFP-DC mice provide a novel tool to monitor DC trafficking and characteristics during allograft rejection. We show rapid migration of dDCs to recipient lymphoid tissues as early as 3 h post-islet allotransplantation. Compared with rDCs, dDCs express different patterns of chemokine receptors, display differential proliferative capacity, and exhibit a higher level of maturity; these findings could be attributed to the effects of injury that dDCs undergo during islet cell preparation and engraftment. Intriguingly, we detected dDCs in the spleen of recipients long after rejection of islet allografts. Given that dDCs express high levels of CCR7, islets were cultured before transplant with the ligand for CCR7 (CCL21). This novel method, which enabled us to enhance the efflux of dDCs from islet preparations, resulted in a prolongation of islet allograft survival in immunocompetent recipients. This study introduces dDCs and rDCs as two distinct types of DCs and provides novel data with clinical implications to use chemokine-based DC-depleting strategies to prolong islet allograft survival. PMID- 17287464 TI - Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells. AB - Adiponectin protects the vascular system partly through stimulation of endothelial nitric oxide (NO) production and endothelium-dependent vasodilation. The current study investigated the role of two recently identified adiponectin receptors, AdipoR1 and -R2, and their downstream effectors in mediating the endothelium actions of adiponectin. In human umbilical vein endothelial cells, adiponectin-induced phosphorylation of endothelial NO synthase (eNOS) at Ser(1177) and NO production were abrogated when expression of AdipoR1 and -R2 were simultaneously suppressed. Proteomic analysis demonstrated that the cytoplasmic tails of both AdipoR1 and -R2 interacted with APPL1, an adaptor protein that contains a PH (pleckstrin homology) domain, a PTB (phosphotyrosine binding) domain, and a Leucine zipper motif. Suppression of APPL1 expression by RNA interference significantly attenuated adiponectin-induced phosphorylation of AMP-activated protein kinase (AMPK) at Thr(172) and eNOS at Ser(1177), and the complex formation between eNOS and heat shock protein 90, resulting in a marked reduction of NO production. Adenovirus-mediated overexpression of a constitutively active version of AMPK reversed these changes. In db/db diabetic mice, both APPL1 expression and adiponectin-induced vasodilation were significantly decreased compared with their lean littermates. Taken together, these results suggest that APPL1 acts as a common downstream effector of AdipoR1 and -R2, mediating adiponectin-evoked endothelial NO production and endothelium dependent vasodilation. PMID- 17287466 TI - Pathogenesis of spinally mediated hyperalgesia in diabetes. AB - Hyperalgesia to noxious stimuli is accompanied by increased spinal cyclooxygenase (COX)-2 protein in diabetic rats. The present studies were initiated to establish causality between increased spinal COX-2 activity and hyperalgesia during diabetes and to assess the potential involvement of polyol pathway activity in the pathogenesis of spinally mediated hyperalgesia. Rats with 1, 2, or 4 weeks of streptozotocin-induced diabetes exhibited significantly increased levels of spinal COX-2 protein and activity, along with exaggerated paw flinching in response to 0.5% paw formalin injection. Increased flinching of diabetic rats was attenuated by intrathecal pretreatment with a selective COX-2 inhibitor immediately before formalin injection, confirming the involvement of COX-2 activity in diabetic hyperalgesia. Chronic treatment with insulin or ICI222155, an aldose reductase inhibitor (ARI) previously shown to prevent spinal polyol accumulation and formalin-evoked hyperalgesia in diabetic rats, prevented elevated spinal COX-2 protein and activity in diabetic rats. In contrast, the ARI IDD676 had no effect on spinal polyol accumulation, elevated spinal COX-2, or hyperalgesia to paw formalin injection. In the spinal cord, aldose reductase immunoreactivity was present solely in oligodendrocytes, which also contained COX 2 immunoreactivity. Polyol pathway flux in spinal oligodendrocytes provides a pathogenic mechanism linking hyperglycemia to hyperalgesia in diabetic rats. PMID- 17287467 TI - Direct free fatty acid uptake into human adipocytes in vivo: relation to body fat distribution. AB - We sought to assess whether direct uptake of circulating free fatty acids (FFAs) by adipocytes occurs in vivo in overnight postabsorptive humans and, if so, whether there are regional differences in uptake between lean and obese women and men. We used bolus injections of radiolabeled FFA tracers followed by carefully timed adipose tissue biopsies. First, we validated a method to measure direct adipocyte FFA uptake and then quantitated this process using the modified methods in normal-weight postabsorptive men and women. We then used a continuous infusion of radiolabeled FFA to measure direct and indirect (VLDL) regional adipose tissue uptake in obese men and women. Direct FFA uptake was greater in women than men: 8.2 +/- 0.6 vs. 4.0 +/- 0.5% (P < 0.0001) of FFAs were taken up by subcutaneous adipose tissue, respectively. Abdominal subcutaneous fat took up FFAs more avidly than femoral fat in men, but this did not occur in women. Similar sex and regional difference were found to occur in obese women and men. Gene expression of fatty acid transporters was greater in abdominal than femoral fat in men (P < 0.05) but not in women (P = 0.80). We observed sex- and site-specific recycling of circulating FFAs into subcutaneous fat. This is a novel FFA disposal pathway that may also play a role in the development or maintenance of body fat distribution. Regional variations in facilitated fatty acid transport may contribute to this process. PMID- 17287468 TI - Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. AB - Although excess visceral fat is associated with noninfectious inflammation, it is not clear whether visceral fat is simply associated with or actually causes metabolic disease in humans. To evaluate the hypothesis that visceral fat promotes systemic inflammation by secreting inflammatory adipokines into the portal circulation that drains visceral fat, we determined adipokine arteriovenous concentration differences across visceral fat, by obtaining portal vein and radial artery blood samples, in 25 extremely obese subjects (mean +/- SD BMI 54.7 +/- 12.6 kg/m(2)) during gastric bypass surgery at Barnes-Jewish Hospital in St. Louis, Missouri. Mean plasma interleukin (IL)-6 concentration was approximately 50% greater in the portal vein than in the radial artery in obese subjects (P = 0.007). Portal vein IL-6 concentration correlated directly with systemic C-reactive protein concentrations (r = 0.544, P = 0.005). Mean plasma leptin concentration was approximately 20% lower in the portal vein than in the radial artery in obese subjects (P = 0.0002). Plasma tumor necrosis factor-alpha, resistin, macrophage chemoattractant protein-1, and adiponectin concentrations were similar in the portal vein and radial artery in obese subjects. These data suggest that visceral fat is an important site for IL-6 secretion and provide a potential mechanistic link between visceral fat and systemic inflammation in people with abdominal obesity. PMID- 17287469 TI - Ca2+/calmodulin-dependent protein kinase kinase-alpha regulates skeletal muscle glucose uptake independent of AMP-activated protein kinase and Akt activation. AB - Studies in nonmuscle cells have demonstrated that Ca(2+)/calmodulin-dependent protein kinase kinases (CaMKKs) are upstream regulators of AMP-activated protein kinase (AMPK) and Akt. In skeletal muscle, activation of AMPK and Akt has been implicated in the regulation of glucose uptake. The objective of this study was to determine whether CaMKKalpha regulates skeletal muscle glucose uptake, and whether it is dependent on AMPK and/or Akt activation. Expression vectors containing constitutively active CaMKKalpha (caCaMKKalpha) or empty vector were transfected into mouse muscles by in vivo electroporation. After 2 weeks, caCaMKKalpha was robustly expressed and increased CaMKI (Thr(177/180)) phosphorylation, a known CaMKK substrate. In muscles from wild-type mice, caCaMKKalpha increased in vivo [(3)H]-2-deoxyglucose uptake 2.5-fold and AMPKalpha1 and -alpha2 activities 2.5-fold. However, in muscles from AMPKalpha2 inactive mice (AMPKalpha2i), caCaMKKalpha did not increase AMPKalpha1 or -alpha2 activities, but it did increase glucose uptake 2.5-fold, demonstrating that caCaMKKalpha stimulates glucose uptake independent of AMPK. Akt (Thr(308)) phosphorylation was not altered by CaMKKalpha, and caCaMKKalpha plus insulin stimulation did not increase the insulin-induced phosphorylation of Akt (Thr(308)). These results suggest that caCaMKKalpha stimulates glucose uptake via insulin-independent signaling mechanisms. To assess the role of CaMKK in contraction-stimulated glucose uptake, isolated muscles were treated with or without the CaMKK inhibitor STO-609 and then electrically stimulated to contract. Contraction increased glucose uptake 3.5-fold in muscles from both wild-type and AMPKalpha2i mice, but STO-609 significantly decreased glucose uptake (approximately 24%) only in AMPKalpha2i mice. Collectively, these results implicate CaMKKalpha in the regulation of skeletal muscle glucose uptake independent of AMPK and Akt activation. PMID- 17287470 TI - The ATP-binding cassette transporter A1 R230C variant affects HDL cholesterol levels and BMI in the Mexican population: association with obesity and obesity related comorbidities. AB - Although ATP-binding cassette transporter A1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation, it is expressed in various tissues, where it may have different functions. Because hypoalphalipoproteinemia is highly prevalent in Mexico, we screened the ABCA1 coding sequence in Mexican individuals with low and high HDL cholesterol levels to seek functional variants. A highly frequent nonsynonymous variant (R230C) was identified in low-HDL cholesterol but not in high-HDL cholesterol individuals (P = 0.00006). We thus assessed its frequency in the Mexican-Mestizo general population, seeking possible associations with several metabolic traits. R230C was screened in 429 Mexican Mestizos using Taqman assays, and it was found in 20.1% of these individuals. The variant was significantly associated not only with decreased HDL cholesterol and apolipoprotein A-I levels but also with obesity (odds ratio 2.527, P = 0.005), the metabolic syndrome (1.893, P = 0.0007), and type 2 diabetes (4.527, P = 0.003). All of these associations remained significant after adjusting for admixture (P = 0.011, P = 0.001, and P = 0.006, respectively). This is the first study reporting the association of an ABCA1 variant with obesity and obesity related comorbidities as being epidemiologically relevant in the Mexican population. PMID- 17287472 TI - Images in clinical medicine. Hydrofluoric acid burn. PMID- 17287473 TI - Taking TRIPS to India--Novartis, patent law, and access to medicines. PMID- 17287471 TI - Variants in ARHGEF11, a candidate gene for the linkage to type 2 diabetes on chromosome 1q, are nominally associated with insulin resistance and type 2 diabetes in Pima Indians. AB - A prior genome-wide linkage scan in Pima Indians indicated a young-onset (aged <45 years) type 2 diabetes susceptibility locus on chromosome 1q21-q23. ARHGEF11, which encodes the Rho guanine nucleotide exchange factor 11, was analyzed as a positional candidate gene for this linkage because this protein may stimulate Rho dependent signals, such as the insulin signaling cascade. The ARHGEF11 gene, and two adjacent genes NTRK1 and INSRR, were sequenced in 24 Pima Indians who were not first-degree relatives. Sequencing of the coding regions, 5' and 3' untranslated regions and putative promoter regions of these genes, identified 28 variants in ARHGEF11, 11 variants in NTRK1, and 8 variants in INSSR. These 47 variants, as well as 84 additional public database variants within/between these genes, were genotyped for association analysis in the same group of Pima Indians who had participated in the linkage study (n = 1,228). An R1467H in ARHGEF11, and several additional noncoding variants that were in high linkage disequilibrium with this variant, were nominally associated with young-onset type 2 diabetes (P = 0.01; odds ratio 3.39) after adjusting for sex, family membership, and Pima heritage. The risk allele H had a frequency of 0.10. In a subgroup of 262 nondiabetic, full-heritage Pima Indians who had undergone detailed metabolic testing, the risk allele H also was associated with a lower mean insulin-mediated glucose disposal rate and a lower mean nonoxidative glucose storage rate after adjusting for age, sex, nuclear family membership, and percentage of body fat (P < or = 0.01). These findings suggest that variation within ARHGEF11 nominally increases risk of type 2 diabetes, possibly as a result of increased insulin resistance. PMID- 17287474 TI - Thailand and the compulsory licensing of efavirenz. PMID- 17287475 TI - Pulmonary alveolar proteinosis--is host defense awry? PMID- 17287476 TI - Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. AB - BACKGROUND: The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior. METHODS: We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery. RESULTS: The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combination-therapy group (P<0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group. The rates of first-trimester pregnancy loss did not differ significantly among the groups. However, the conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combination-therapy group (46.0%, P<0.001). With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. CONCLUSIONS: Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861 [ClinicalTrials.gov].). PMID- 17287477 TI - GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis. AB - BACKGROUND: Increased mortality from infection in patients with pulmonary alveolar proteinosis occurs in association with high levels of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). We tested the hypothesis that neutrophil functions are impaired in patients with pulmonary alveolar proteinosis and that GM-CSF autoantibodies cause the dysfunction. METHODS: We studied 12 subjects with pulmonary alveolar proteinosis, 61 healthy control subjects, and 12 control subjects with either cystic fibrosis or end stage liver disease. We also studied GM-CSF-/- mice and wild-type mice. We evaluated basal neutrophil functions, neutrophil functions after priming by GM CSF to augment antimicrobial functions, and the effects of highly purified GM-CSF autoantibodies on neutrophil functions in vitro and in vivo. RESULTS: Neutrophils from subjects with pulmonary alveolar proteinosis had normal ultrastructure and differentiation markers but impaired basal functions and antimicrobial functions after GM-CSF priming. GM-CSF-/- mice also had reduced basal neutrophil functions, but functions after GM-CSF priming were unimpaired. The neutrophil dysfunction characteristic of pulmonary alveolar proteinosis was reproduced in a dose dependent fashion in blood specimens from healthy control subjects after incubation with affinity-purified GM-CSF autoantibodies isolated from patients with pulmonary alveolar proteinosis. The injection of mouse GM-CSF antibodies into wild-type mice also caused neutrophil dysfunction. CONCLUSIONS: The antimicrobial functions of neutrophils are impaired in patients with pulmonary alveolar proteinosis, owing to the presence of GM-CSF autoantibodies. The effects of these autoantibodies show that GM-CSF is an essential regulator of neutrophil functions. PMID- 17287478 TI - A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. AB - BACKGROUND: Skin-infiltrating lymphocytes expressing type 1 cytokines have been linked to the pathophysiology of psoriasis. We evaluated the safety and efficacy of a human interleukin-12/23 monoclonal antibody in treating psoriasis. METHODS: In this double-blind, placebo-controlled trial, 320 patients with moderate-to severe plaque psoriasis underwent randomization to treatment with the interleukin 12/23 monoclonal antibody (one 45-mg dose, one 90-mg dose, four weekly 45-mg doses, or four weekly 90-mg doses) or placebo; 64 patients were randomly assigned to each group. Patients assigned to the interleukin-12/23 monoclonal antibody received one additional dose at week 16 if needed. Patients assigned to placebo crossed over to receive one 90-mg dose of interleukin-12/23 monoclonal antibody at week 20. RESULTS: There was at least 75% improvement in the psoriasis area-and severity index at week 12 (the primary end point) in 52% of patients who received 45 mg of the interleukin-12/23 monoclonal antibody, in 59% of those who received 90 mg, in 67% of those who received four weekly 45-mg doses, and in 81% of those who received four weekly 90-mg doses, as compared with 2% of those who received placebo (P<0.001 for each comparison), and there was at least 90% improvement in 23%, 30%, 44%, and 52%, respectively, of patients who received the monoclonal antibody as compared with 2% of patients who received placebo (P<0.001 for each comparison). Adverse events occurred in 79% of patients treated with the interleukin-12/23 monoclonal antibody as compared with 72% of patients in the placebo group (P=0.19). Serious adverse events occurred in 4% of patients who received the monoclonal antibody and in 1% of those who received placebo (P=0.69). CONCLUSIONS: This study demonstrates the therapeutic efficacy of an interleukin-12/23 monoclonal antibody in psoriasis and provides further evidence of a role of the interleukin-12/23 p40 cytokines in the pathophysiology of psoriasis. Larger studies are needed to determine whether serious adverse events might limit the clinical usefulness of this new therapeutic target. (ClinicalTrials.gov number, NCT00320216 [ClinicalTrials.gov].). PMID- 17287480 TI - Clinical practice. The incidentally discovered adrenal mass. PMID- 17287479 TI - Religion, conscience, and controversial clinical practices. AB - BACKGROUND: There is a heated debate about whether health professionals may refuse to provide treatments to which they object on moral grounds. It is important to understand how physicians think about their ethical rights and obligations when such conflicts emerge in clinical practice. METHODS: We conducted a cross-sectional survey of a stratified, random sample of 2000 practicing U.S. physicians from all specialties by mail. The primary criterion variables were physicians' judgments about their ethical rights and obligations when patients request a legal medical procedure to which the physician objects for religious or moral reasons. These procedures included administering terminal sedation in dying patients, providing abortion for failed contraception, and prescribing birth control to adolescents without parental approval. RESULTS: A total of 1144 of 1820 physicians (63%) responded to our survey. On the basis of our results, we estimate that most physicians believe that it is ethically permissible for doctors to explain their moral objections to patients (63%). Most also believe that physicians are obligated to present all options (86%) and to refer the patient to another clinician who does not object to the requested procedure (71%). Physicians who were male, those who were religious, and those who had personal objections to morally controversial clinical practices were less likely to report that doctors must disclose information about or refer patients for medical procedures to which the physician objected on moral grounds (multivariate odds ratios, 0.3 to 0.5). CONCLUSIONS: Many physicians do not consider themselves obligated to disclose information about or refer patients for legal but morally controversial medical procedures. Patients who want information about and access to such procedures may need to inquire proactively to determine whether their physicians would accommodate such requests. PMID- 17287481 TI - Images in clinical medicine. Urine fluorescence in ethylene glycol poisoning. PMID- 17287483 TI - Treating the polycystic ovary syndrome the old-fashioned way. PMID- 17287482 TI - Case records of the Massachusetts General Hospital. Case 4-2007. A 56-year-old woman with rapidly progressive vertigo and ataxia. PMID- 17287484 TI - Regulatory and judicial oversight of nonprofit hospitals. PMID- 17287485 TI - Colonoscopy screening for detection of advanced neoplasia. PMID- 17287487 TI - DHEA and testosterone in the elderly. PMID- 17287489 TI - Medical education--professionalism. PMID- 17287488 TI - Spinal epidural abscess. PMID- 17287486 TI - Antithymocyte globulin versus basiliximab in renal transplantation. PMID- 17287490 TI - Thoracentesis. PMID- 17287492 TI - Ethnicity and diet of children: development of culturally sensitive measures. AB - Obesity is a growing global concern. Examining dietary habits of individuals can facilitate the development of important prevention approaches, which are needed to decrease the incidence of obesity and other related diseases and improve quality of life indices. Because food preferences and dietary habits vary across cultures, it is essential that prevention programs are based on specific populations. Using both ethnographic and quantitative methods, food-consumption patterns were investigated among 1,125 children in the Commonwealth of the Northern Mariana Islands. Differences were observed related to food frequency, age of children, and grade level. Exploratory factor analyses suggested that the individual foods were best organized into food-consumption groups that reflected cultural characteristics rather than more commonly referenced food organizational systems. In addition to developmental differences in food consumption patterns, results suggest that the ethnicity of parents may play a role in the diet of children. PMID- 17287491 TI - Elderly survivors with homozygous sickle cell disease. PMID- 17287495 TI - Positive association, in local release, of luteal oxytocin with endothelin 1 and prostaglandin F2alpha during spontaneous luteolysis in the cow: a possible intermediatory role for luteolytic cascade within the corpus luteum. AB - Luteolysis is caused by a pulsatile release of prostaglandin F(2alpha) (PGF(2alpha)) from the uterus in ruminants, and a positive feedback between endometrial PGF(2alpha) and luteal oxytocin (OXT) has a physiologic role in the promotion of luteolysis. The bovine corpus luteum (CL) produces vasoactive substances, such as endothelin 1 (EDN1) and angiotensin II (Ang II), that mediate and progress luteolysis. We hypothesized that luteal OXT has an additive function to ensure the CL regression with EDN1 and Ang II, and that it has an active role in the luteolytic cascade in the cow. Thus, the aim of the present study was to observe real-time changes in the local secretion of luteal OXT and to determine its relationship with other local mediators of luteolysis. Microdialysis system (MDS) capillary membranes were implanted surgically into each CL of six cyclic Holstein cows (18 lines total among the six cows) on Day 15 (estrus == Day 0) of the estrous cycle. Simultaneously, catheters were implanted to collect ovarian venous plasma ipsilateral to the CL. Although the basal secretion of OXT by luteal tissue was maintained during the experimental period, the intraluteal PGF(2alpha) secretion gradually increased up to 300% from 24 h after the onset of luteolysis (0 h; time in which progesterone started to decrease). In each MDS line (microenvironment) within the CL, the local releasing profiles of OXT were positively associated with PGF(2alpha) and EDN1 within the CL in all 18 MDS lines implanted in the six CLs (OXT vs. PGF(2alpha), 50.0%; OXT vs. EDN1, 72.2%; P < 0.05). On the other hand, the intraluteal OXT was weakly related to Ang II (OXT vs. Ang II, 27.7%). In the ovarian vein, the peak concentration of PGF(2alpha) increased significantly when the peak of PGF(2alpha) coincided with the peak of OXT after the onset of spontaneous luteolysis (P < 0.05). In conclusion, intraluteal OXT may locally modulate secretion of vasoactive substances, particularly EDN1 and PGF(2alpha) within the CL, and thus might be one of the luteal mediators of spontaneous luteolysis in the cow. PMID- 17287494 TI - Gene expression profiling and its relevance to the blood-epididymal barrier in the human epididymis. AB - The luminal environment along the epididymal duct is important for spermatozoal maturation. This environment is unique and created by the blood-epididymal barrier, which is formed by tight and adhering junctions. For the human epididymis, little information exists on the proteins that comprise these junctions. Our objectives were to assess the gene expression profiles in the different segments of the human epididymis and to identify the proteins that make up the blood-epididymal barrier. Using microarrays, we identified 2980 genes that were differentially expressed by at least 2-fold between the various segments. Of the many genes involved in diverse functions, were those that encoded adhesion proteins (cadherins and catenins) and tight junctional proteins (claudins [CLDN] and others). PCR analyses confirmed the microarray data. Immunolocalization of CLDNs 1, 3, 4, 8, and 10 revealed that the localization of CLDNs differed along the epididymis. In all three segments, CLDNs 1, 3, and 4 were localized to tight junctions, along the lateral margins of adjacent principal cells, and at the interface between basal and principal cells. CLDN8 was localized to tight junctions in all three segments, in addition to being localized in the caput along the lateral margins of principal cells, and in the corpus, at the interface between principal and basal cells. CLDN10, tight junction protein 1, and occludin were localized exclusively to tight junctions in all three epididymal segments. These data indicate that the epididymis displays a complex pattern of gene expression, which includes genes that are implicated in the formation of the blood-epididymal barrier, which suggests complex regulation of this barrier. PMID- 17287496 TI - Allocation of gamma-tubulin between oocyte cortex and meiotic spindle influences asymmetric cytokinesis in the mouse oocyte. AB - In oocytes, asymmetric cytokinesis represents a conserved strategy for karyokinesis during meiosis to retain ooplasmic maternal factors needed after fertilization. Given the role of gamma-tubulin in cell cycle progression and microtubule dynamics, this study focused on gamma-tubulin as a key regulator of asymmetric cytokinesis in mouse oocytes. Gamma-tubulin properties were studied using multiple-label digital imaging, Western blots, quantitative RT-PCR, and microinjection strategies in mouse oocytes matured in vivo (IVO) or in vitro (IVM). Quantitative image analysis established that IVO oocytes extrude smaller first polar bodies (PBs), contain smaller spindles, and have more cytoplasmic microtubule organizing centers (MTOCs) relative to IVM oocytes. Maturation in culture was shown to alter gamma-tubulin distribution, as evidenced by incorporation throughout the meiotic spindle and within the first PB. Western blot analysis confirmed that total gamma-tubulin content remained elevated in IVM oocytes compared with IVO oocytes. Analysis of gamma-tubulin mRNA during maturation revealed fluctuations in IVO oocytes, whereas IVM oocytes maintained relatively stable at lower levels for the time points examined (0-16 h). Selective reduction of gamma-tubulin mRNA by injection of siRNA diminished both spindle and PB size, whereas overexpression of enhanced green fluorescent protein gamma-tubulin had the opposite effect. Together, these studies reinforce the notion that limiting gamma-tubulin availability during meiotic maturation ensures coordination of karyokinesis and cytokinesis and conservation of gamma-tubulin as an embryonic reserve. PMID- 17287497 TI - Recurrent circuits in layer II of medial entorhinal cortex in a model of temporal lobe epilepsy. AB - Patients and laboratory animal models of temporal lobe epilepsy display loss of layer III pyramidal neurons in medial entorhinal cortex and hyperexcitability and hypersynchrony of less vulnerable layer II stellate cells. We sought to test the hypothesis that loss of layer III pyramidal neurons triggers synaptic reorganization and formation of recurrent, excitatory synapses among layer II stellate cells in epileptic pilocarpine-treated rats. Laser-scanning photo uncaging of glutamate focally activated neurons in layer II while excitatory synaptic responses were recorded in stellate cells. Photostimulation revealed previously unidentified, functional, recurrent, excitatory synapses between layer II stellate cells in control animals. Contrary to the hypothesis, however, control and epileptic rats displayed similar levels of recurrent excitation. Recently, hyperexcitability of layer II stellate cells has been attributed, at least in part, to loss of GABAergic interneurons and inhibitory synaptic input. To evaluate recurrent inhibitory circuits in layer II, we focally photostimulated interneurons while recording inhibitory synaptic responses in stellate cells. IPSCs were evoked more than five times more frequently in slices from control versus epileptic animals. These findings suggest that in this model of temporal lobe epilepsy, reduced recurrent inhibition contributes to layer II stellate cell hyperexcitability and hypersynchrony, but increased recurrent excitation does not. PMID- 17287501 TI - Similar neural representations of the target for saccades and perception during search. AB - Are the body's actions and the mind's perceptions the result of shared neural processing, or are they performed largely independently? The brain has two major processing streams, and some have proposed that this division segregates visual processing for action and perception. The ventral pathway is claimed to support conscious experience (perception), whereas the dorsal pathway is claimed to support the control of movement (action). Others have argued that perception and action share much of their visual processing within the primate cortex. During visual search, the brain performs a sophisticated deployment of eye movements (saccadic actions) to gather information to subserve perceptual judgments. The relationship between the neural mechanisms mediating perception and action in visual search remains unexplored. Here, we investigate the visual representation of target information in the human brain, both for perceptual decisions and for saccadic actions during visual search. We use classification image analysis, a form of reverse correlation, to estimate the behavioral receptive fields of the visual mechanisms responsible for saccadic and perceptual responses during the same visual search task. Results show that the behavioral receptive fields mediating the perceptual decisions are indistinguishable from those driving the oculomotor decisions, suggesting that similar neural mechanisms are responsible for both perception and oculomotor action during search. Diverging target representations would result in an inefficient coupling between eye movement planning and perceptual judgments. Thus, a common target representation would be more optimal and might be expected to have evolved through natural selection in the neural systems responsible for visual search. PMID- 17287493 TI - Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. AB - Aging-related erectile dysfunction is characterized by a loss of smooth muscle cells (SMCs) and fibrosis in the corpora cavernosa, and functionally by corporal veno-occlusive dysfunction (CVOD). Phosphodiesterase 5 (PDE5A) inhibitors, in part via upregulating inducible nitric oxide synthase (NOS2A), have antifibrotic properties in penile tissues. We aimed to determine whether in the aged rat the chronic long-term treatment with sildenafil ameliorates corporal SMC loss and fibrosis, stimulates NOS2A induction, and corrects the associated CVOD. Aged male rats (20 mo old) received sildenafil in their drinking water (20 mg/kg per day) or plain water for 45 days, and untreated young rats (5 mo old) served as controls (n = 8 per group). CVOD was assessed by dynamic infusion cavernosometry (DIC). Collagen:SMC (Masson trichrome) and collagen III:I (picrosirius red) ratios, SMC content (alpha-smooth muscle actin [ACTA2]), cell proliferation (proliferating nuclear antigen [PCNA]), apoptotic death (TUNEL), and NOS2A induction were measured by histochemistry and immunohistochemistry followed by quantitative image analysis. Collagen content was determined by hydroxyproline assay, and transforming growth factor beta-1 (TGFB1); xanthine oxidoreductase (XDH); ACTA2; NOS2A; and the Rho kinase inhibitor protein tyrosine phosphatase, nonreceptor type 11 (PTPN11), and activator, VAV, were measured by quantitative Western blot. In the aged rats treated with sildenafil, the erectile response by DIC was normalized, and the corporal SMC:collagen ratio and SMC number were increased. In addition, sildenafil reduced the corporal collagen content without affecting the collagen III:I ratio, increased the PCNA:apoptosis ratio, and stimulated NOS2A induction, although there was no effect on XDH, TGFB1, PTPN11, or VAV levels. These data show that long-term PDE5A treatment corrected CVOD in the aged rat and partially reversed the aging-related fibrosis and loss of SMC in the corpora cavernosa without affecting TGFB1 or PTPN11 levels, which are markers of oxidative stress. It may be speculated that similar effects may be achieved with this paradigm in men. PMID- 17287500 TI - Smelling a single component of male sweat alters levels of cortisol in women. AB - Rodents use chemosignals to alter endocrine balance in conspecifics. Although responses to human sweat suggest a similar mechanism in humans, no particular component of human sweat capable of altering endocrine balance in conspecifics has yet been isolated and identified. Here, we measured salivary levels of the hormone cortisol in women after smelling pure androstadienone (4,16-androstadien 3-one), a molecule present in the sweat of men that has been suggested as a chemosignal in humans. We found that merely smelling androstadienone maintained significantly higher levels of the hormone cortisol in women. These results suggest that, like rodents, humans can influence the hormonal balance of conspecifics through chemosignals. Critically, this study identified a single component of sweat, androstadienone, as capable of exerting such influence. This result points to a potential role for synthetic human chemosignals in clinical applications. PMID- 17287498 TI - The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. AB - The anesthetic isoflurane has been reported to induce apoptosis and increase Abeta generation and aggregation. However, the molecular mechanism underlying these effects remains unknown. We therefore set out to assess whether the effects of isoflurane on apoptosis are linked to amyloid beta-protein (Abeta) generation and aggregation. For this purpose, we assessed the effects of isoflurane on beta site amyloid beta precursor protein (APP)-cleaving enzyme (BACE) and gamma secretase, the proteases responsible for Abeta generation. We also tested the effects of inhibitors of Abeta aggregation (iAbeta5, a beta-sheet breaker peptide; clioquinol, a copper-zinc chelator) on the ability of isoflurane to induce apoptosis. All of these studies were performed on naive human H4 neuroglioma cells as well as those overexpressing APP (H4-APP cells). Isoflurane increased the levels of BACE and gamma-secretase and secreted Abeta in the H4-APP cells. Isoflurane-induced Abeta generation could be blocked by the broad-based caspase inhibitor Z-VAD. The Abeta aggregation inhibitors, iAbeta5 and clioquinol, selectively attenuated caspase-3 activation induced by isoflurane. However, isoflurane was able to induce caspase-3 activation in the absence of any detectable alterations of Abeta generation in naive H4 cells. Finally, Abeta potentiated the isoflurane-induced caspase-3 activation in naive H4 cells. Collectively, these findings suggest that isoflurane can induce apoptosis, which, in turn, increases BACE and gamma-secretase levels and Abeta secretion. Isoflurane also promotes Abeta aggregation. Accumulation of aggregated Abeta in the media can then promote apoptosis. The result is a vicious cycle of isoflurane induced apoptosis, Abeta generation and aggregation, and additional rounds of apoptosis, leading to cell death. PMID- 17287499 TI - Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain. AB - Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth. PMID- 17287502 TI - Spike timing-dependent synaptic depression in the in vivo barrel cortex of the rat. AB - Spike timing-dependent plasticity (STDP) is a computationally powerful form of plasticity in which synapses are strengthened or weakened according to the temporal order and precise millisecond-scale delay between presynaptic and postsynaptic spiking activity. STDP is readily observed in vitro, but evidence for STDP in vivo is scarce. Here, we studied spike timing-dependent synaptic depression in single putative pyramidal neurons of the rat primary somatosensory cortex (S1) in vivo, using two techniques. First, we recorded extracellularly from layer 2/3 (L2/3) and L5 neurons, and paired spontaneous action potentials (postsynaptic spikes) with subsequent subthreshold deflection of one whisker (to drive presynaptic afferents to the recorded neuron) to produce "post-leading-pre" spike pairings at known delays. Short delay pairings (<17 ms) resulted in a significant decrease of the extracellular spiking response specific to the paired whisker, consistent with spike timing-dependent synaptic depression. Second, in whole-cell recordings from neurons in L2/3, we paired postsynaptic spikes elicited by direct-current injection with subthreshold whisker deflection to drive presynaptic afferents to the recorded neuron at precise temporal delays. Post-leading-pre pairing (<33 ms delay) decreased the slope and amplitude of the PSP evoked by the paired whisker, whereas "pre-leading-post" delays failed to produce depression, and sometimes produced potentiation of whisker-evoked PSPs. These results demonstrate that spike timing-dependent synaptic depression occurs in S1 in vivo, and is therefore a plausible plasticity mechanism in the sensory cortex. PMID- 17287503 TI - The spatial organization of long-term synaptic plasticity at the input stage of cerebellum. AB - The spatial organization of long-term synaptic plasticity [long-term potentiation (LTP) and long-term depression (LTD)] is supposed to play a critical role for distributed signal processing in neuronal networks, but its nature remains undetermined in most central circuits. By using multielectrode array recordings, we have reconstructed activation maps of the granular layer in cerebellar slices. LTP and LTD induced by theta-burst stimulation appeared in patches organized in such a way that, on average, LTP was surrounded by LTD. The sign of long-term synaptic plasticity in a given granular layer region was directly correlated with excitation and inversely correlated with inhibition: the most active areas tended to generate LTP, whereas the least active areas tended to generate LTD. Plasticity was almost entirely prevented by application of the NMDA receptor blocker, APV. This suggests that synaptic inhibition, through a control of membrane depolarization, effectively regulates NMDA channel unblock, postsynaptic calcium entry, and the induction of bidirectional synaptic plasticity at the mossy fiber-granule cell relay (Gall et al., 2005). By this mechanism, LTP and LTD could regulate the geometry and contrast of network computations, preprocessing the mossy fiber input to be conveyed to Purkinje cells and molecular layer interneurons. PMID- 17287505 TI - Age-related differences in neuromagnetic brain activity underlying concurrent sound perception. AB - Deficits in parsing concurrent auditory events are believed to contribute to older adults' difficulties in understanding speech in adverse listening conditions (e.g., cocktail party). To explore the level at which aging impairs sound segregation, we measured auditory evoked fields (AEFs) using magnetoencephalography while young, middle-aged, and older adults were presented with complex sounds that either had all of their harmonics in tune or had the third harmonic mistuned by 4 or 16% of its original value. During the recording, participants were asked to ignore the stimuli and watch a muted subtitled movie of their choice. For each participant, the AEFs were modeled with a pair of dipoles in the superior temporal plane, and the effects of age and mistuning were examined on the amplitude and latency of the resulting source waveforms. Mistuned stimuli generated an early positivity (60-100 ms), an object-related negativity (ORN) (140-180 ms) that overlapped the N1 and P2 waves, and a positive displacement that peaked at approximately 230 ms (P230) after sound onset. The early mistuning-related enhancement was similar in all three age groups, whereas the subsequent modulations (ORN and P230) were reduced in older adults. These age differences in auditory cortical activity were associated with a reduced likelihood of hearing two sounds as a function of mistuning. The results reveal that inharmonicity is rapidly and automatically registered in all three age groups but that the perception of concurrent sounds declines with age. PMID- 17287506 TI - Developmental cell death is enhanced in the cerebral cortex of mice lacking the brain vesicular monoamine transporter. AB - Neurotransmitters have emerged as important players in the control of programmed cell death in the cerebral cortex. We report that genetic depletion of serotonin, dopamine, and norepinephrine in mice lacking the vesicular monoamine transporter (VMAT2 KO mice) causes an increase in cell death in the superficial layers of the cingulate and retrosplenial cortices during early postnatal life (postnatal days 0-4). Electron microscopy and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling indicated that this represents a form of apoptosis. Caspase-3 and -9 are over activated in the VMAT2 KO cortex and Bcl X(L) is downregulated, whereas the apoptosis-inducing factor caspase-8 and FasL/FasR pathway are not involved. Partial inhibition of serotonin or/and catecholamine synthesis by pharmacological treatments or genetic reduction of serotonin neuron number in mice lacking the transcription factor Pet-1 (pheochromocytoma 12 E26 transformation-specific) did not modify the cell death ratios in the cerebral cortex. However, when monoamine oxidase type A was invalidated in the VMAT2 KO background (VMAT2-MAOA DKO mice), increases in 5-HT levels coincided with a reduction of cell death and a normalization of Bcl-X(L) expression. trkB signaling is not implicated in the anti-apoptotic effects of MAOA inhibition because BDNF mRNA levels were unchanged in VMAT2-MAOA DKO mice and because the massive cell death in the cerebral cortex of trkB KO mice is also reverted by genetic invalidation of the MAOA gene. Finally the broad 5-HT2 receptor agonist (-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride prevented the increase in cell death of VMAT2 KO mice. Altogether, these results suggest that high levels of serotonin, acting through 5-HT2 receptors, have neuroprotective action on cortical neurons by controlling Bcl-X(L) mRNA levels and that this action is independent of trkB signaling. PMID- 17287504 TI - The nociceptin/orphanin FQ receptor antagonist J-113397 and L-DOPA additively attenuate experimental parkinsonism through overinhibition of the nigrothalamic pathway. AB - By using a battery of behavioral tests, we showed that nociceptin/orphanin FQ receptor (NOP receptor) antagonists attenuated parkinsonian-like symptoms in 6 hydroxydopamine hemilesioned rats (Marti et al., 2005). We now present evidence that coadministration of the NOP receptor antagonist 1-[(3R,4R)-1 cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H benzimidazol 2-one (J-113397) and L-DOPA to 6-hydroxydopamine hemilesioned rats produced an additive attenuation of parkinsonism. To investigate the neurobiological substrates underlying this interaction, in vivo microdialysis was used in combination with behavioral measurements (bar test). J-113397 and L-DOPA alone reduced the time on bars (i.e., attenuated akinesia) and elevated GABA release selectively in the lesioned substantia nigra reticulata. J-113397 also reduced nigral glutamate levels, whereas L-DOPA was ineffective. J-113397 and L-DOPA coadministration produced additive antiakinetic effect, which was associated with additive increase in nigral GABA release but no additional reductions in glutamate levels. To investigate whether the increase in nigral GABA release could translate to changes in nigrothalamic transmission, GABA release was monitored in the ventromedial thalamus (one of the main target areas of the nigrothalamic projections). J-113397 and L-DOPA decreased thalamic GABA release and attenuated akinesia, their combination resulting in a more profound effect. These actions were prevented by perfusing the voltage-dependent Na+ channel blocker tetrodotoxin or the GABA(A) receptor antagonist bicuculline in the substantia nigra reticulata. These data demonstrate that J-113397 and L-DOPA exert their antiparkinsonian action through overinhibition of nigrothalamic transmission and suggest that NOP receptor antagonists may be useful as an adjunct to L-DOPA therapy for Parkinson's disease. PMID- 17287507 TI - Retrograde regulation of GABA transmission by the tonic release of oxytocin and endocannabinoids governs postsynaptic firing. AB - The probability of neurotransmitter release at the nerve terminal is an important determinant of synaptic efficacy. At some central synapses, the postsynaptic, or target, neuron determines neurotransmitter release probability (P(r)) at the presynaptic terminal. The mechanisms responsible for this target-cell dependent control of P(r) have not been elucidated. Using whole-cell patch-clamp recordings from magnocellular neurosecretory cells in the paraventricular and supraoptic nuclei of the hypothalamus, we demonstrate that inhibitory, GABA synapses specifically onto oxytocin (OT)-producing neurosecretory cells exhibit a low P(r) that is relatively uniform at multiple synapses onto the same cell. This low P(r) results from a two-step process that requires the tonic release of OT from the postsynaptic cell. The ambient extracellular levels of neuropeptide are sufficient to activate postsynaptic OT receptors and trigger the Ca2+-dependent production of endocannabinoids, which act in a retrograde manner at presynaptic cannabinoid CB1 receptors to decrease GABA release. The functional consequence of this tonic inhibition of GABA release is that all inhibitory inputs facilitate uniformly when activated at high rates of activity. This causes inhibition in the postsynaptic cell that is sufficiently powerful to disrupt firing. Blockade of CB1 receptors increases P(r) at these synapses, resulting in a rapid depression of IPSCs at high rates of activity, thereby eliminating the ability of afferent inputs to inhibit postsynaptic firing. By playing a deterministic role in GABA release at the afferent nerve terminal, the postsynaptic OT neuron effectively filters synaptic signals and thereby modulates its own activity patterns. PMID- 17287508 TI - Altered effective connectivity within the language network in primary progressive aphasia. AB - Primary progressive aphasia (PPA) is a neurodegenerative dementia syndrome principally characterized by the gradual dissolution of language functions, especially in the early stages of disorder. In a previous functional neuroimaging study, PPA patients were found to activate core language areas similarly to control subjects when performing semantic and phonological processing tasks (Sonty et al., 2003). In the present study, functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) were used to study multiregional effective connectivity in early-stage PPA (n = 8) and control (n = 8) subjects performing semantic word matching and visual letter matching tasks. fMRI analysis showed semantic task-specific activations in the left inferior frontal (Broca's area) and posterior superior temporal (Wernicke's area) regions, in addition to other language regions, in both groups. Using a model language network consisting of six left hemisphere regions, the DCM analysis demonstrated reduced language specific effective connectivity between Wernicke's and Broca's areas in the PPA patient group. Furthermore, this decrement in connectivity was predictive of semantic task accuracy. These results demonstrate for the first time that dysfunctional network interactions (effective connectivity), rather than hypoactivity within individual brain regions, may contribute to the emergence of language deficits seen in PPA. PMID- 17287509 TI - A reevaluation of the inverse dynamic model for eye movements. AB - To construct an appropriate motor command from signals that provide a representation of desired action, the nervous system must take into account the dynamic characteristics of the motor plant to be controlled. In the oculomotor system, signals specifying desired eye velocity are thought to be transformed into motor commands by an inverse dynamic model of the eye plant that is shared for all types of eye movements and implemented by a weighted combination of eye velocity and position signals. Neurons in the prepositus hypoglossi and adjacent medial vestibular nuclei (PH-BT neurons) were traditionally thought to encode the "eye position" component of this inverse model. However, not only are PH-BT responses inconsistent with this theoretical role, but compensatory eye movement responses to translation do not show evidence for processing by a common inverse dynamic model. Prompted by these discrepancies between theoretical notions and experimental observations, we reevaluated these concepts using multiple-frequency rotational and translational head movements. Compatible with the notion of a common inverse model, we show that PH-BT responses are unique among all premotor cell types in bearing a consistent relationship to the motor output during eye movements driven by different sensory stimuli. However, because their responses are dynamically identical to those of motoneurons, PH-BT neurons do not simply represent an internal component of the inverse model, but rather its output. They encode and distribute an estimate of the motor command, a signal critical for accurate motor execution and learning. PMID- 17287510 TI - Gender-specific left-right asymmetries in human visual cortex. AB - The structural correlates of gender differences in visuospatial processing are essentially unknown. Our quantitative analysis of the cytoarchitecture of the human primary visual cortex [V1/Brodmann area 17 (BA17)], neighboring area V2 (BA18), and the cytoarchitectonic correlate of the motion-sensitive complex (V5/MT+/hOc5) shows that the visual areas are sexually dimorphic and that the type of dimorphism differs among the areas. Gender differences exist in the interhemispheric asymmetry of hOc5 volumes and in the right-hemispheric volumetric ratio of hOc5 to BA17, an area that projects to V5/MT+/hOc5. Asymmetry was also observed in the surface area of hOc5 but not in its cortical thickness. The differences give males potentially more space in which to process additional information, a finding consistent with superior male processing in particular visuospatial tasks, such as mental rotation. Gender differences in hOc5 exist with similar volume fractions of cell bodies, implying that, overall, the visual neural circuitry is similar in males and females. PMID- 17287511 TI - GABAergic interneurons facilitate mossy fiber excitability in the developing hippocampus. AB - Profound activity-dependent synaptic facilitation at hippocampal mossy fiber synapses is a unique and functionally important property. Although presynaptic ionotropic receptors, such as kainate receptors, contribute partially to the facilitation in the hippocampus, the precise mechanisms of presynaptic regulation by endogenous neurotransmitters remain unclear. In this study, we report that axonal GABA(A) receptors on mossy fibers are involved in the activity-dependent facilitation during development. In immature mouse hippocampal slices, short train stimulation (five pulses at 25 Hz) caused frequency-dependent facilitation of not only postsynaptic responses but also presynaptic fiber volleys that represent presynaptic activities. This fiber volley facilitation was inhibited by selective GABA(A) receptor antagonists, or by enkephalin that selectively suppresses excitability of interneurons. Furthermore, we directly demonstrated that this facilitation resulted from depolarization of mossy fibers in imaging experiments using a voltage-sensitive dye. This increased mossy fiber excitability caused by depolarizing action of GABA gradually decreased with development and eventually disappeared at around postnatal day 30. These results suggested that GABA released from interneurons acted on axonal GABA(A) receptors on mossy fibers and contributed at least partially to the activity- and age dependent facilitation in the hippocampus. PMID- 17287512 TI - Erbin enhances voltage-dependent facilitation of Ca(v)1.3 Ca2+ channels through relief of an autoinhibitory domain in the Ca(v)1.3 alpha1 subunit. AB - Ca(v)1.3 (L-type) voltage-gated Ca2+ channels have emerged as key players controlling Ca2+ signals at excitatory synapses. Compared with the more widely expressed Ca(v)1.2 L-type channel, relatively little is known about the mechanisms that regulate Ca(v)1.3 channels. Here, we describe a new role for the PSD-95 (postsynaptic density-95)/Discs large/ZO-1 (zona occludens-1) (PDZ) domain containing protein, erbin, in directly potentiating Ca(v)1.3. Erbin specifically forms a complex with Ca(v)1.3, but not Ca(v)1.2, in transfected cells. The significance of erbin/Ca(v)1.3 interactions is supported by colocalization in somatodendritic domains of cortical neurons in culture and coimmunoprecipitation from rat brain lysates. In electrophysiological recordings, erbin augments facilitation of Ca(v)1.3 currents by a conditioning prepulse, a process known as voltage-dependent facilitation (VDF). This effect requires a direct interaction of the erbin PDZ domain with a PDZ recognition site in the C-terminal domain (CT) of the long variant of the Ca(v)1.3 alpha1 subunit (alpha1 1.3). Compared with Ca(v)1.3, the Ca(v)1.3b splice variant, which lacks a large fraction of the alpha1 1.3 CT, shows robust VDF that is not further affected by erbin. When coexpressed as an independent entity with Ca(v)1.3b or Ca(v)1.3 plus erbin, the alpha1 1.3 CT strongly suppresses VDF, signifying an autoinhibitory function of this part of the channel. These modulatory effects of erbin, but not alpha1 1.3 CT, depend on the identity of the auxiliary Ca2+ channel beta subunit. Our findings reveal a novel mechanism by which PDZ interactions and alternative splicing of alpha1 1.3 may influence activity-dependent regulation of Ca(v)1.3 channels at the synapse. PMID- 17287513 TI - Primed vesicles can be distinguished from docked vesicles by analyzing their mobility. AB - Neurotransmitters are released from nerve terminals and neuroendocrine cells by calcium-dependent exocytosis of vesicles. Before fusion, vesicles are docked to the plasma membrane and rendered release competent through a process called priming. Electrophysiological methods such as membrane capacitance measurements and carbon fiber amperometry accurately measure the fusion step of exocytosis with high time resolution but provide only indirect information about priming and docking. Total internal reflection fluorescence microscopy (TIRFM) enables the real-time visualization of vesicles, near the plasma membrane, as they undergo changes from one molecular state to the other. We devised a new method to analyze the mobility of vesicles, which not only allowed us to classify the movement of vesicles in three different categories but also to monitor dynamic changes in the mobility of vesicles over time. We selectively enhanced priming by treating bovine chromaffin cells with phorbol myristate acetate (PMA) or by overexpressing Munc13-1 (mammalian Unc) and analyzed the mobility of large dense-core vesicles. We demonstrate that nearly immobile vesicles represent primed vesicles because the pool of vesicles displaying this type of mobility was significantly increased after PMA treatment and Munc13-1 overexpression and decreased during tetanus toxin expression. Moreover, we showed that the movement of docked but unprimed vesicles is restricted to a confined region of approximately 220 nm diameter. Finally, a small third population of undocked vesicles showed a directed and probably active type of mobility. For the first time, we can thus distinguish the molecular state of vesicles in TIRFM by their mobility. PMID- 17287514 TI - Differential spatial representation of taste modalities in the rat gustatory cortex. AB - Discrimination between foods is crucial for the nutrition and survival of animals. Remarkable progress has been made through molecular and genetic manipulations in the understanding of the coding of taste at the receptor level. However, much less is known about the cortical processing of taste sensation and the organizing principles of the gustatory cortex (GC). Using genetic tracing, it has recently been shown that sweet and bitter taste are processed through segregated neuronal circuitries along the gustatory pathway up to the cortical level. This is in disagreement with the evidence that GC neurons recorded in both anesthetized and behaving animals responded to multiple taste modalities (including sweet and bitter). To investigate the functional architecture of the GC in regard to taste modalities, we used in vivo intrinsic optical imaging, a technique that has been successfully applied to explore the organization of other neocortical regions. We found that four of the primary taste modalities (sweet, bitter, salty, and sour) are represented by distinctive spatial patterns but that no region was specific to a single modality. In addition, we found that two tastants of similar hedonic value (pleasant or unpleasant) activated areas with more common regions than two tastants with opposite hedonic value. In summary, we propose that these specific cortical patterns can be used to discriminate among various tastants. PMID- 17287515 TI - Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. AB - Lewy bodies, the pathological hallmark of dementia with Lewy bodies (DLB), are large juxtanuclear inclusions of aggregated alpha-synuclein. However, the small number of cortical Lewy bodies relative to the total neuron count does not correlate with the extent of cognitive impairment. In contrast to dopaminergic neurons in Parkinson's disease, nerve cell loss is usually less prevalent in the cortex of DLB, suggesting a different mechanism of neurodegeneration. Because antibodies used for immunodetection per se do not generally differentiate the aggregated from the physiological and monomeric isoform of alpha-synuclein, we developed the paraffin-embedded tissue (PET) blot and the protein aggregate filtration (PAF) assay for the sensitive and selective detection of alpha synuclein aggregates in tissue slides and brain homogenates, respectively. In contrast to common immunohistochemistry, the PET blot detected an enormous number of small alpha-synuclein aggregates, which, in contrast to the few Lewy bodies, may explain the cognitive impairment in DLB. Using the PAF assay, we demonstrate that the absolute majority of alpha-synuclein aggregates are located at presynaptic terminals, suggesting a severe pathological impact on synaptic function. Indeed, parallel to the massive presynaptic accumulation of alpha synuclein aggregates, we observed significant synaptic pathology with almost complete loss of dendritic spines at the postsynaptic area. Our results provide strong evidence for a novel concept of neurodegeneration for DLB in which synaptic dysfunction is caused by presynaptic accumulation of alpha-synuclein aggregates. This concept may also be valid for Parkinson's disease. PMID- 17287516 TI - G alpha(q)-coupled muscarinic acetylcholine receptors enhance nicotinic acetylcholine receptor signaling in Caenorhabditis elegans mating behavior. AB - In this study, we address why metabotropic and ionotropic cholinergic signaling pathways are used to facilitate motor behaviors. We demonstrate that a G alpha(q) coupled muscarinic acetylcholine receptor (mAChR) signaling pathway enhances nicotinic acetylcholine receptor (nAChR) signaling to facilitate the insertion of the Caenorhabditis elegans male copulatory spicules into the hermaphrodite during mating. Previous studies showed that ACh (acetylcholine) activates nAChRs on the spicule protractor muscles to induce the attached spicules to extend from the tail. Using the mAChR agonist Oxo M (oxotremorine M), we identified a GAR 3(mAChR)-G alpha(q) pathway that promotes protractor muscle contraction by upregulating nAChR signaling before mating. GAR-3(mAChR) is expressed in the protractor muscles and in the spicule-associated SPC and PCB cholinergic neurons. However, ablation of these neurons or impairing cholinergic transmission reduces drug-induced spicule protraction, suggesting that drug-stimulated neurons directly activate muscle contraction. Behavioral analysis of gar-3 mutants indicates that, in wild-type males, GAR-3(mAChR) expression in the SPC and PCB neurons is required for the male to sustain rhythmic spicule muscle contractions during attempts to breach the vulva. We propose that the GAR-3(mAChR)/G alpha(q) pathway sensitizes the spicule neurons and muscles before and during mating so that the male can respond to hermaphrodite vulva efficiently. PMID- 17287517 TI - Estrogen regulates Bcl-w and Bim expression: role in protection against beta amyloid peptide-induced neuronal death. AB - Estrogen is neuroprotective against a variety of insults, including beta-amyloid peptide (Abeta); however, the underlying mechanism(s) is not fully understood. Here, we report that 17beta-estradiol (E2) selectively regulates neuronal expression of the Bcl-2 family (bcl-2, bcl-x, bcl-w, bax, bak, bad, bik, bnip3, bid, and bim). In primary cerebrocortical neuron cultures under basal conditions, we observe that E2 upregulates expression of antiapoptotic Bcl-w and downregulates expression of proapoptotic Bim in an estrogen receptor (ER) dependent manner. In the presence of toxic levels of Abeta, we observe that E2 attenuates indices of neuronal apoptosis: c-Jun N-terminal kinase (JNK)-dependent downregulation of Bcl-w and upregulation of Bim, mitochondrial release of cytochrome c and Smac, and cell death. These neuroprotective effects of E2 against Abeta-induced apoptosis are mimicked by the JNK inhibitor SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one). In addition, E2 attenuates Abeta-induced JNK phosphorylation in an ER-dependent manner, but does not affect basal levels of JNK phosphorylation. These results suggest that E2 may reduce Abeta-induced neuronal apoptosis at least in part by two complementary pathways: (1) ER dependent, JNK-independent upregulation of Bcl-w and downregulation of Bim under basal conditions, and (2) ER-dependent inhibition of Abeta-induced JNK activation and subsequent JNK-dependent downregulation of Bcl-w and upregulation of Bim, resulting in mitochondrial release of cytochrome c and Smac and eventual cell death. These data provide new understanding into the mechanisms contributing to estrogen neuroprotection, a neural function with potential therapeutic relevance to Alzheimer's disease. PMID- 17287518 TI - p19(Ink4d) and p21(Cip1) collaborate to maintain the postmitotic state of auditory hair cells, their codeletion leading to DNA damage and p53-mediated apoptosis. AB - Sensory hair cells of the auditory organ are generated during embryogenesis and remain postmitotic throughout life. Previous work has shown that inactivation of the cyclin-dependent kinase inhibitor (CKI) p19(Ink4d) leads to progressive hearing loss attributable to inappropriate DNA replication and subsequent apoptosis of hair cells. Here we show the synergistic action of another CKI, p21(Cip1), on cell cycle reactivation. The codeletion of p19(Ink4d) and p21(Cip1) triggered profuse S-phase entry of auditory hair cells during a restricted period in early postnatal life, leading to the transient appearance of supernumerary hair cells. In addition, we show that aberrant cell cycle reentry leads to activation of a DNA damage response pathway in these cells, followed by p53 mediated apoptosis. The majority of hair cells were absent in adult cochleas. These data, together with the demonstration of changing expression patterns of multiple CKIs in auditory hair cells during the stages of early postnatal maturation, show that the maintenance of the postmitotic state is an active, tissue-specific process, cooperatively regulated by several CKIs, and is critical for the lifelong survival of these sensory cells. PMID- 17287519 TI - Roles of volume-sensitive chloride channel in excitotoxic neuronal injury. AB - Excitotoxicity is associated with stroke, brain trauma, and a number of neurodegenerative disorders. In the brain, during excitotoxic insults, neurons undergo rapid swelling in both the soma and dendrites. Focal swellings along the dendrites called varicosities are considered to be a hallmark of acute excitotoxic neuronal injury. However, it is not clear what pathway is involved in the neuronal anion flux that leads to the formation and resolution of excitotoxic varicosities. Here, we assessed the roles of the volume-sensitive outwardly rectifying (VSOR) Cl- channel in excitotoxic responses in mouse cortical neurons. Whole-cell patch-clamp recordings revealed that the VSOR Cl- channel in cultured neurons was activated by NMDA exposure. Moreover, robust expression of this channel on varicosities was confirmed by on-cell and nystatin-perforated vesicle patch techniques. VSOR channel blockers, but not blockers of GABA(A) receptors and Cl- transporters, abolished not only varicosity resolution after sublethal excitotoxic stimulation but also necrotic death after sustained varicosity formation induced by prolonged NMDA exposure in cortical neurons. The present slice-patch experiments demonstrated, for the first time, expression of the VSOR Cl- channels in somatosensory pyramidal neurons. NMDA-induced necrotic neuronal death in slice preparations was largely suppressed by a blocker of the VSOR Cl- channel but not of the GABA(A) receptor. These results indicate that VSOR Cl- channels exert dual, reciprocal actions on neuronal excitotoxicity by serving as major anionic pathways both for varicosity recovery after washout of an excitotoxic stimulant and for persistent varicosity formation under prolonged excitotoxic insults leading to necrosis in cortical neurons. PMID- 17287520 TI - Identification of an intersubunit cross-link between substituted cysteine residues located in the putative ATP binding site of the P2X1 receptor. AB - P2X receptors are ATP-gated nonselective cation channels. Functional receptors are assembled as homotrimers or heterotrimers of seven cloned subunits. Each subunit contains two transmembrane domains linked by a large extracellular loop that is required for agonist binding. So far, there is no direct evidence indicating whether the agonist binding site is formed within one subunit or at the interface of two neighboring subunits. Here we used a disulfide cross-linking approach to identify pairs of residues that are in close proximity within the ATP binding site of the P2X1 homotrimer. Eight amino acid residues that have previously been shown to be essential for high ATP potency (K68, K70, F185, K190, F291, R292, R305, and K309) were substituted by cysteine residues, and the respective mutant subunits were pairwise expressed in Xenopus laevis oocytes. Nonreducing SDS-PAGE analysis of the purified receptors revealed a spontaneous and specific dimer formation between the K68C and F291C mutants. An almost complete cross-link into trimers was achieved with the K68C/F291C double mutant, consistent with the formation of intersubunit disulfide bridges. In support of this interpretation, two-electrode voltage-clamp analysis of the K68C/F291C mutations introduced into a nondesensitizing P2X(2-1) chimera showed only small ATP-activated currents that, however, increased approximately 60-fold after extracellular application of the reducing agent dithiothreitol. In addition, we show that a K68C/K309C double mutant is nonfunctional and can be functionally rescued by coexpression with nonmutated subunits. Our data are consistent with loops from neighboring P2X subunits forming the ATP-binding site in P2X receptors. PMID- 17287521 TI - Early life stress alters adult serotonin 2C receptor pre-mRNA editing and expression of the alpha subunit of the heterotrimeric G-protein G q. AB - Infant maternal separation, a paradigm of early life stress in rodents, elicits long-lasting changes in gene expression that persist into adulthood. In BALB/c mice, an inbred strain with spontaneously elevated anxiety and stress reactivity, infant maternal separation led to increased depression-like behavioral responses to adult stress and robustly increased editing of serotonin 2C receptor pre-mRNA. Chronic fluoxetine treatment of adult BALB/c mice exposed to early life stress affected neither their behavioral responses to stress nor their basal 5-HT2C pre mRNA editing phenotype. However, when fluoxetine was administered during adolescence, depression-like behavioral responses to stress were significantly diminished in these mice, and their basal and stress-induced 5-HT2C pre-mRNA editing phenotypes were significantly lower. Moreover, when BALB/c mice exposed to early life stress were raised in an enriched postweaning environment, their depression-like behavioral responses to adult stress were also significantly diminished. However, their 5-HT2C pre-mRNA editing phenotype remained unaltered. Hence, the similar behavioral effects of enrichment and fluoxetine treatment during adolescence were not accompanied by similar changes in 5-HT2C pre-mRNA editing. Enriched and nonenriched BALB/c mice exposed to early life stress also exhibited significantly increased expression of mRNA and protein encoding the G alpha q subunit of G-protein that couples to 5-HT2A/2C receptors. In contrast, G alpha q expression levels were significantly lower in fluoxetine-treated mice. These findings suggest that compensatory changes in G alpha q expression occur in mice with persistently altered 5-HT2C pre-mRNA editing and provide an explanation for the dissociation between 5-HT2C receptor editing phenotypes and behavioral stress responses. PMID- 17287522 TI - Sphingosine 1-phosphate (S1P) signaling is required for maintenance of hair cells mainly via activation of S1P2. AB - Hearing requires the transduction of vibrational forces by specialized epithelial cells in the cochlea known as hair cells. The human ear contains a finite number of terminally differentiated hair cells that, once lost by noise-induced damage or toxic insult, can never be regenerated. We report here that sphingosine 1 phosphate (S1P) signaling, mainly via activation of its cognate receptor S1P2, is required for the maintenance of vestibular and cochlear hair cells in vivo. Two S1P receptors, S1P2 and S1P3, were found to be expressed in the cochlea by reverse transcription-PCR and in situ hybridization. Mice that are null for both these receptors uniformly display progressive cochlear and vestibular defects with hair cell loss, resulting in complete deafness by 4 weeks of age and, with complete penetrance, balance defects of increasing severity. This study reveals the previously unknown role of S1P signaling in the maintenance of cochlear and vestibular integrity and suggests a means for therapeutic intervention in degenerative hearing loss. PMID- 17287523 TI - The neural code of auditory phantom perception. AB - Tinnitus is defined by an auditory perception in the absence of an external source of sound. This condition provides the distinctive possibility of extracting neural coding of perceptual representation. Previously, we had established that tinnitus is characterized by enhanced magnetic slow-wave activity (approximately 4 Hz) in perisylvian or putatively auditory regions. Because of works linking high-frequency oscillations to conscious sensory perception and positive symptoms in a variety of disorders, we examined gamma band activity during brief periods of marked enhancement of slow-wave activity. These periods were extracted from 5 min of resting spontaneous magnetoencephalography activity in 26 tinnitus and 21 control subjects. Results revealed the following, particularly within a frequency range of 50-60 Hz: (1) Both groups showed significant increases in gamma band activity after onset of slow waves. (2) Gamma is more prominent in tinnitus subjects than in controls. (3) Activity at approximately 55 Hz determines the laterality of the tinnitus perception. Based on present and previous results, we have concluded that cochlear damage, or similar types of deafferentation from peripheral input, triggers reorganization in the central auditory system. This produces permanent alterations in the ongoing oscillatory dynamics at the higher layers of the auditory hierarchical stream. The change results in enhanced slow-wave activity reflecting altered corticothalamic and corticolimbic interplay. Such enhancement facilitates and sustains gamma activity as a neural code of phantom perception, in this case auditory. PMID- 17287524 TI - Xenopus vocalizations are controlled by a sexually differentiated hindbrain central pattern generator. AB - Male and female African clawed frogs (Xenopus laevis) produce rhythmic, sexually distinct vocalizations as part of courtship and mating. We found that Xenopus vocal behavior is governed by a sexually dimorphic central pattern generator (CPG) and that fictive vocalizations can be elicited from an in vitro brain preparation by application of serotonin or by electrical stimulation of a premotor nucleus. Male brains produced fictive vocal patterns representing two calls commonly produced by males in vivo (advertisement and amplectant call), as well as one call pattern (release call) that is common for juvenile males and females in vivo but rare for adult males. Female brains also produced fictive release call. The production of male calls is androgen dependent in Xenopus; to test the effects of androgens on the CPG, we examined fictive calling in the brains of testosterone-treated females. Both fictive male advertisement call and release call were produced. This suggests that all Xenopus possess a sexually undifferentiated pattern generator for release call. Androgen exposure leads to a gain-of-function, allowing the production of male-specific call types without prohibiting the production of the undifferentiated call pattern. We also demonstrate that the CPG is located in the brainstem and seems to rely on the same nuclei in both males and females. Finally, we identified endogenous serotonergic inputs to both the premotor and motor nuclei in the brainstem that may regulate vocal activity in vivo. PMID- 17287525 TI - Hypo-osmolar stress induces p75NTR expression by activating Sp1-dependent transcription. AB - Injury-induced expression of the p75 neurotrophin receptor (p75NTR) in the CNS facilitates neuronal apoptosis and prevents neuronal regrowth, but the mechanisms regulating p75NTR expression are poorly characterized. In this study, we showed that hypo-osmolarity induces p75NTR expression in primary neurons, and, using a comparative genomics approach, we identified conserved elements in the 25 kb upstream sequences of the rat, mouse, and human p75NTR genes. We found that only one of these, a proximal region rich in Sp1 sites, responds to changes in hypo osmolarity. We then showed that Sp1 DNA binding activity is increased in cells exposed to hypo-osmolarity, established that hypo-osmolarity enhanced Sp1 binding to the endogenous p75NTR promoter, and showed that Sp1 is required for p75NTR expression induced by hypo-osmolarity. We examined how Sp1 is regulated to effect these changes and established that Sp1 turnover is strongly inhibited by hypo osmolarity. We propose that stress-induced Sp1 accumulation that results from reductions in Sp1 turnover rate contributes to injury-induced gene expression. PMID- 17287526 TI - Ssh4, Rcr2 and Rcr1 affect plasma membrane transporter activity in Saccharomyces cerevisiae. AB - Nutrient uptake in the yeast Saccharomyces cerevisiae is a highly regulated process. Cells adjust levels of nutrient transporters within the plasma membrane at multiple stages of the secretory and endosomal pathways. In the absence of the ER-membrane-localized chaperone Shr3, amino acid permeases (AAP) inefficiently fold and are largely retained in the ER. Consequently, shr3 null mutants exhibit greatly reduced rates of amino acid uptake due to lower levels of AAPs in their plasma membranes. To further our understanding of mechanisms affecting AAP localization, we identified SSH4 and RCR2 as high-copy suppressors of shr3 null mutations. The overexpression of SSH4, RCR2, or the RCR2 homolog RCR1 increases steady-state AAP levels, whereas the genetic inactivation of these genes reduces steady-state AAP levels. Additionally, the overexpression of any of these suppressor genes exerts a positive effect on phosphate and uracil uptake systems. Ssh4 and Rcr2 primarily localize to structures associated with the vacuole; however, Rcr2 also localizes to endosome-like vesicles. Our findings are consistent with a model in which Ssh4, Rcr2, and presumably Rcr1, function within the endosome-vacuole trafficking pathway, where they affect events that determine whether plasma membrane proteins are degraded or routed to the plasma membrane. PMID- 17287527 TI - Reduced X-linked diversity in derived populations of house mice. AB - Contrasting patterns of X-linked vs. autosomal diversity may be indicative of the mode of selection operating in natural populations. A number of observations have shown reduced X-linked (or Z-linked) diversity relative to autosomal diversity in various organisms, suggesting a large impact of genetic hitchhiking. However, the relative contribution of other forces such as population bottlenecks, variation in reproductive success of the two sexes, and differential introgression remains unclear. Here, we survey 13 loci, 6 X-linked and 7 autosomal, in natural populations of the house mouse (Mus musculus) subspecies complex. We studied seven populations of three different subspecies, the eastern house mouse M. musculus castaneus, the central house mouse M. m. musculus, and the western house mouse M. m. domesticus, including putatively ancestral and derived populations for each. All populations display lower diversity on the X chromosomes relative to autosomes, and this effect is most pronounced in derived populations. To assess the role of demography, we fit the demographic parameters that gave the highest likelihood of the data using coalescent simulations. We find that the reduction in X-linked diversity is too large to be explained by a simple demographic model in at least two of four derived populations. These observations are also not likely to be explained by differences in reproductive success between males and females. They are consistent with a greater impact of positive selection on the X chromosome, and this is supported by the observation of an elevated K(A) and elevated K(A)/K(S) ratios on the rodent X chromosome. A second contribution may be that the X chromosome less readily introgresses across subspecies boundaries. PMID- 17287528 TI - The sex-determining locus in the tiger pufferfish, Takifugu rubripes. AB - The tiger pufferfish (fugu), Takifugu rubripes, is a model fish that has had its genome entirely sequenced. By performing genomewide linkage analyses, we show that the sex of fugu is determined by a single chromosomal region on linkage group 19 in an XX-XY system. PMID- 17287529 TI - Analysis of a triple testcross design with recombinant inbred lines reveals a significant role of epistasis in heterosis for biomass-related traits in Arabidopsis. AB - Primary causes of heterosis are still unknown. Our goal was to investigate the extent and underlying genetic causes of heterosis for five biomass-related traits in Arabidopsis thaliana. We (i) investigated the relative contribution of dominance and epistatic effects to heterosis in the hybrid C24 x Col-0 by generation means analysis and estimates of variance components based on a triple testcross (TTC) design with recombinant inbred lines (RILs), (ii) estimated the average degree of dominance, and (iii) examined the importance of reciprocal and maternal effects in this cross. In total, 234 RILs were crossed to parental lines and their F1's. Midparent heterosis (MPH) was high for rosette diameter at 22 days after sowing (DAS) and 29 DAS, growth rate (GR), and biomass yield (BY). Using the F2-metric, directional dominance prevailed for the majority of traits studied but reciprocal and maternal effects were not significant. Additive and dominance variances were significant for all traits. Additive x additive and dominance x dominance variances were significant for all traits but GR. We conclude that dominance as well as digenic and possibly higher-order epistatic effects play an important role in heterosis for biomass-related traits. Our results encourage the use of Arabidopsis hybrid C24 x Col-0 for identification and description of quantitative trait loci (QTL) for heterosis for biomass related traits and further genomic studies. PMID- 17287530 TI - Identification of quantitative trait loci and environmental interactions for accumulation and remobilization of water-soluble carbohydrates in wheat (Triticum aestivum L.) stems. AB - Genetic analyses of nine traits associated with stem water-soluble carbohydrate (SWSC) accumulation and remobilization at grain-filling period under drought stress (DS) and well-watered (WW) conditions were undertaken using doubled haploid lines (DHLs) derived from two Chinese common wheat cultivars. Some significantly and very significantly positive correlation was observed among nine traits associated with SWSC. Higher phenotypic values for most traits were detected under DS. Broad sense heritabilities (h(B)(2)) of the traits showed wide fluctuations between two water treatments. A total of 48 additive and 62 pairs of epistatic QTL for nine traits were identified as distributing on all 21 chromosomes. A majority of QTL involved significant additive and epistatic effects with interactions of QTL and environments (QEIs). Two additive and two pairs of epistatic loci involved only QEIs without corresponding significant additive or epistatic effects. The contributions of the additive QEIs were two- to fourfolds higher than those of their corresponding additive QTL. Most of the additive QEIs for traits associated with SWSC interacted with DS. In addition, some QTL for the grain-filling efficiencies and thousand-grain weight were colocated in the same or adjacent chromosome intervals with QTL for accumulation and remobilization efficiency of SWSC before 14 days after flowering. PMID- 17287531 TI - Valproic acid affects membrane trafficking and cell-wall integrity in fission yeast. AB - Valproic acid (VPA) is widely used to treat epilepsy and manic-depressive illness. Although VPA has been reported to exert a variety of biochemical effects, the exact mechanisms underlying its therapeutic effects remain elusive. To gain further insights into the molecular mechanisms of VPA action, a genetic screen for fission yeast mutants that show hypersensitivity to VPA was performed. One of the genes that we identified was vps45+, which encodes a member of the Sec1/Munc18 family that is implicated in membrane trafficking. Notably, several mutations affecting membrane trafficking also resulted in hypersensitivity to VPA. These include ypt3+ and ryh1+, both encoding a Rab family protein, and apm1+, encoding the mu1 subunit of the adaptor protein complex AP-1. More importantly, VPA caused vacuolar fragmentation and inhibited the glycosylation and the secretion of acid phosphatase in wild-type cells, suggesting that VPA affects membrane trafficking. Interestingly, the cell-wall-damaging agents such as micafungin or the inhibition of calcineurin dramatically enhanced the sensitivity of wild-type cells to VPA. Consistently, VPA treatment of wild-type cells enhanced their sensitivity to the cell-wall-digesting enzymes. Altogether, our results suggest that VPA affects membrane trafficking, which leads to the enhanced sensitivity to cell-wall damage in fission yeast. PMID- 17287532 TI - Evolutionary strata on the X chromosomes of the dioecious plant Silene latifolia: evidence from new sex-linked genes. AB - Despite its recent evolutionary origin, the sex chromosome system of the plant Silene latifolia shows signs of progressive suppression of recombination having created evolutionary strata of different X-Y divergence on sex chromosomes. However, even after 8 years of effort, this result is based on analyses of five sex-linked gene sequences, and the maximum divergence (and thus the age of this plant's sex chromosome system) has remained uncertain. More genes are therefore needed. Here, by segregation analysis of intron size variants (ISVS) and single nucleotide polymorphisms (SNPs), we identify three new Y-linked genes, one being duplicated on the Y chromosome, and test for evolutionary strata. All the new genes have homologs on the X and Y chromosomes. Synonymous divergence estimated between the X and Y homolog pairs is within the range of those already reported. Genetic mapping of the new X-linked loci shows that the map is the same in all three families that have been studied so far and that X-Y divergence increases with genetic distance from the pseudoautosomal region. We can now conclude that the divergence value is saturated, confirming the cessation of X-Y recombination in the evolution of the sex chromosomes at approximately 10-20 MYA. PMID- 17287533 TI - Highly variable patterns of linkage disequilibrium in multiple soybean populations. AB - Prospects for utilizing whole-genome association analysis in autogamous plant populations appear promising due to the reported high levels of linkage disequilibrium (LD). To determine the optimal strategies for implementing association analysis in soybean (Glycine max L. Merr.), we analyzed the structure of LD in three regions of the genome varying in length from 336 to 574 kb. This analysis was conducted in four distinct groups of soybean germplasm: 26 accessions of the wild ancestor of soybean (Glycine soja Seib. et Zucc.); 52 Asian G. max Landraces, the immediate results of domestication from G. soja; 17 Asian Landrace introductions that became the ancestors of North American (N. Am.) cultivars, and 25 Elite Cultivars from N. Am. In G. soja, LD did not extend past 100 kb; however, in the three cultivated G. max groups, LD extended from 90 to 574 kb, likely due to the impacts of domestication and increased self fertilization. The three genomic regions were highly variable relative to the extent of LD within the three cultivated soybean populations. G. soja appears to be ideal for fine mapping of genes, but due to the highly variable levels of LD in the Landraces and the Elite Cultivars, whole-genome association analysis in soybean may be more difficult than first anticipated. PMID- 17287534 TI - Observations on the "Lausanne Recommendations" on sudden cardiovascular death in sport. PMID- 17287535 TI - Always look on the bright side.... PMID- 17287536 TI - Manufactured arguments: turning consensus into controversy does not advance science. PMID- 17287539 TI - Fractured fairy tales: hyponatraemia and the American College of Sports Medicine fluid recommendations. PMID- 17287541 TI - Exercise-associated hyponatraemia: facts and myths. PMID- 17287543 TI - India & China: time to catch up. PMID- 17287544 TI - Post-emergency: providing effective, sustainable, life-long care to everyone with AIDS. PMID- 17287545 TI - Capacity building for clinical trials in India. PMID- 17287546 TI - Participation in HIV vaccine trials: listening to participant & community concerns. PMID- 17287547 TI - Iron deficiency in healthy blood donors exposes vulnerability of the nation to iron deficiency. PMID- 17287548 TI - Autologous transplantation in the central nervous system. AB - Cell transplantation has been proposed to replace lost neurons in the diseased brain, and after injuries to the central nervous system (CNS). Strategies for cellular therapy in the CNS consist primarily in heterologous transplantations. Despite the CNS being an immunologically privileged site, immune rejection of intracerebral transplants remains a concern. In addition, the use of immunosuppressive drugs, like cyclosporine, is a major constraint associated with heterologous transplantations. Autologous transplantation is therefore viewed as the model of choice for cellular therapy. With the recent progress in somatic cell nuclear transfer (SCNT) research, and the confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the adult CNS, new opportunities for autologous transplantations are being considered for the CNS, and are promising. PMID- 17287549 TI - Emergence of chronic obstructive pulmonary disease as an epidemic in India. AB - Chronic obstructive pulmonary disease (COPD), hitherto underdiagnosed in India, is now recognized in 4-10 per cent of adult male population of India and several other Asian countries. The Regional COPD Working Group for 12 Asia Pacific Countries and Regions used a COPD prevalence model and estimated an overall prevalence rate of 6.3 per cent with a range from 3.5 to 6.7 per cent. The smoking associations with COPD were high from most countries i.e., 2.65 in India, 2.57 in China and 2.12 in Japan. In a large, multicentric study from India, the population prevalence of COPD was 4.1 per cent of 35295 subjects with a male to female ratio of 1.56:1. Almost all forms of smoking products such as cigarettes and 'bidis' used in different States were found to be significantly associated with COPD. In non-smokers, especially women, exposures to indoor air pollution from domestic combustion of solid fuels was an important factor. More significantly the exposure to environmental tobacco smoke (ETS) was an established cause for COPD. The odds ratio for risk from ETS exposure in non smokers (1.535) was on significant during both the childhood and the adulthood. On an average, an Indian COPD patient spent about 15 per cent of his income on smoking products and up to 30 per cent on disease management. Tobacco smoking was also the most frequent cause of chronic cor pulmonale which occurred as a long term complication of COPD both amongst men and women. PMID- 17287550 TI - A pilot study on willingness to participate in future preventive HIV vaccine trials. AB - BACKGROUND & OBJECTIVES: In India, phase-I human clinical trials for a preventive HIV vaccine are being conducted at Pune and Chennai Centres. In order to find out the willingness of populations at risk to participate in future preventive HIV vaccine trials (HIVVTs) and to assess the factors that enhance or deter them from participation, a study was conducted at Chennai and Madurai in Tamil Nadu. METHODS: This cross-sectional study was conducted among transport workers, people attending sexually transmitted infection clinics, injection drug users, men having sex with men, women in sex industry and a representative sample of monogamous married women, by employing measurement scales. A structured questionnaire on knowledge and attitudes about the HIV vaccine was used to measure the participants' knowledge and attitudes about HIV vaccine and HIVVTs. RESULTS: Of the 112 participants, 67 (60%) were men. Mean age of the respondents was 32 yr; 68 per cent were high school educated. Majority of respondents were willing to participate in a future HIVVT and the reasons were altruism, protection from HIV, and support for the researchers. Major concerns were vaccine efficacy, side effects of the vaccine and the impact of a HIV vaccine on the participants' lives. Majority (85%) agreed that sex without condom would not be safe despite the availability of an HIV vaccine. INTERPRETATION & CONCLUSION: It is likely that high-risk volunteers will be willing to enroll in HIVVTs. Barriers and concerns should be dealt with carefully by providing correct information. Also there is a need for more education to ensure participants' understanding of key concepts of HIV vaccine trial. PMID- 17287551 TI - Evaluation of iron stores in blood donors by serum ferritin. AB - BACKGROUND & OBJECTIVES: Regular blood donation can lead to pre-clinical iron deficiency as well as iron deficiency anaemia. There is a need to increase the national voluntary blood donation for safe blood supply. However, there is paucity of data in the country regarding impact of regular voluntary blood donation on iron status of donors. Hence, iron stores were evaluated by serum ferritin estimation in the voluntary blood donors at Chandigarh. METHODS: 400 voluntary blood donors included in the study were divided into four groups depending upon their periodicity of blood donations. Pre-donation haemoglobin assessment was done by copper sulphate method. Serum ferritin was estimated by indirect ELISA. RESULTS: The number of female donors with deficient iron stores was more as compared to male donors. First time donors had higher mean serum ferritin levels than that in repeat donors. The frequency of donations per year was more predictive of decreased iron stores rather than the number of lifetime donations. An increase in donation frequency was accompanied by a significant decrease in serum ferritin; values <15 microg/l were found in 21 and 46 per cent of male and female donors respectively who donated once per year, in 29 and 27 per cent in those who donated twice per year and in 49 and 100 per cent in those who donated thrice per year. INTERPRETATION & CONCLUSION: Haemoglobin estimation alone in regular blood donors may not be adequate; serum ferritin estimations may need to be done to detect pre-clinical iron deficiency states. Also, iron supplementation needs to be considered in regular, repeat voluntary blood donors. PMID- 17287552 TI - Impact of iron deficiency anaemia on T lymphocytes & their subsets in children. AB - BACKGROUND & OBJECTIVES: While there is evidence of an altered immune profile in iron deficiency, the precise immunoregulatory role of iron is not known. Information particular in children who are vulnerable to iron deficiency and infection, is lacking. We undertook this study with the aim of documenting the changes in T cell subsets in children in the age group of 1 to 5 yr with iron deficiency. METHODS: The levels of T lymphocytes, their CD4+ and CD8+ subsets and the CD4 : CD8 ratio were evaluated in 40 iron deficient and 30 healthy children. The impact of oral iron supplementation for three months on the same parameters was also noted in 30 children. RESULTS: Significantly lower levels of T lymphocytes as well as CD4+ cells was observed in the iron deficient children (P<0.01 and 0.002 respectively). The CD4 : CD8 ratio was also significantly lower in this group (P<0.05). Iron supplementation improved the CD4 counts significantly. INTERPRETATION & CONCLUSION: Our study demonstrated quantitatively altered T cell subsets in iron deficiency in children, and a relationship between the severity of haematological and immunological compromise. The clinical and epidemiological implications of this relationship have topical relevance since ID is the most common micronutrient deficiency worldwide. PMID- 17287553 TI - Cultivation of human corneal limbal stem cells in Mebiol gel--A thermo-reversible gelation polymer. AB - BACKGROUND & OBJECTIVES: Cultivated limbal stem cell transplantation is being used as a current treatment modality for limbal stem cell deficiency. However, use of allogenic biological material as substrate is associated with risks of transmission of certain diseases and allograft rejection. Therefore development of non-toxic biodegradable synthetic polymers is important. We undertook this study to evaluate the use of a synthetic polymer Mebiol gel as a substrate for the growth of limbal phenotype cells and cornea phenotype cells from limbal explants. METHODS: Human cadaveric limbal explants cells were cultivated on Mebiol gel. The proliferative capacity of cultivated cells was analyzed with thymidine incorporation studies. Immunostaining for presumed limbal stem cell association markers and cornea differentiation markers was performed and confirmed with reverse transcription (RT-PCR). RESULTS: The limbal explants underwent proliferation in vitro. The cultivated cells expressed the presumed limbal stem cell association markers (ABCG2 and p63), the transient amplifying cell markers (connexin 43, integrin alpha9) and the cornea differentiation marker (K3). RT PCR confirmed the immunohistochemical data. INTERPRETATION & CONCLUSION: Our findings showed that the synthetic polymer Mebiol gel was able to support limbal explant proliferation. The cultured cells expressed presumed limbal stem cell association markers, transient amplifying cells and cornea phenotype markers. Mebiol Gel can be used as a scaffold for growing limbal explants. PMID- 17287554 TI - Measurement of 24 h energy expenditure in male tuberculosis patients. AB - BACKGROUND & OBJECTIVES: The total daily energy expenditure in patients with infectious disease is presumed to be high because of an increase in the basal metabolic rate (BMR), a reason for the weight loss observed in these patients. A reduction in daily physical activity, which may reduce the total daily energy expenditure. The aim of this study was to measure the free living total daily energy expenditure and physical activity of newly diagnosed hospitalized patients with tuberculosis using the labelled bicarbonate method. METHODS: In 6 healthy volunteers and 6 patients with newly diagnosed tuberculosis, 13C labelled bicarbonate method was used to measure free living total daily energy expenditure and physical activity. The 13C sodium bicarbonate (NaH13CO3) tracer was infused intravenously over a 48 h period and breath samples collected at regular intervals to estimate expired 13CO2. RESULTS: The patients had a 14 per cent increase in their BMR although they were not febrile at the time of measurement. However, their total daily energy expenditure was lower than that of the controls (mean value of 8.3 and 10.3 mJ/day respectively) and their physical activity level was also lower (mean 1.4 and 1.6 units respectively). INTERPRETATION & CONCLUSION: The total daily energy expenditure of afebrile patients with newly diagnosed tuberculosis is not higher than that of sedentary controls, despite an increased basal metabolic rate. It is possible that the observed weight loss in patients with tuberculosis is due to a reduced energy intake linked to anorexia associated with the disease. These findings may have relevance in nutritional treatment of chronic infections. PMID- 17287555 TI - Association between subclinical inflammation & fasting insulin in urban young adult north Indian males. AB - BACKGROUND & OBJECTIVES: Elevated levels of c-reactive protein (CRP) are known to be associated with insulin resistance and metabolic syndrome in adults. A substantial prevalence of hyperinsulinaemia and elevated CRP levels have been shown in Indian young adults. We therefore studied the association of serum high sensitivity C-reactive protein (hs-CRP) with fasting insulin and insulin resistance in urban adolescent and young adult males in north India. METHODS: In this cross-sectional study 324 healthy males, 14-25 yr of age were selected randomly and their clinical and anthropometric profile [body mass index (BMI), waist and hip circumferences, waist-to-hip circumference ratio (W-HR), and skinfold thickness at four sites], percentage of body fat (%BF) and biochemical (fasting blood glucose, lipoprotein profile, fasting insulin and hs-CRP) parameters were recorded. Insulin resistance was assessed by the homeostasis model of assessment (HOMA-IR). RESULTS: Fasting insulin and hs-CRP levels correlated significantly with BMI, waist circumference, and triceps and subscapular skinfold thickness. Fasting insulin also correlated with %BF, and hs- CRP correlated with W-HR. No correlation was observed between hs-CRP and fasting insulin levels or insulin resistance. In multiple logistic regression analysis different independent risk factors for hyperinsulinaemia and elevated hs-CRP levels were observed; hypercholesterolaemia, overweight and high subscapular skinfold thickness for the former, and high triceps skinfold thickness for the latter. INTERPRETATION & CONCLUSION: Lack of correlation between hs-CRP and surrogate markers of insulin resistance and different risk factors for each, in young Indian males are unique observations of our study. Further studies on a larger sample of both genders need to be done to confirm these findings. PMID- 17287556 TI - Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran. AB - BACKGROUND & OBJECTIVES: Endo-derived nitric oxide (NO) is synthesized from L arginine by endothelium nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7. Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; polymorphisms of NOS gene might be associated with increased susceptibility to this disorder and coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in Iranian patients. METHODS: We studied the 27 base pair tandem repeat polymorphism in intron4 of the endothelial nitric oxide synthase (eNOS) gene in 141 unrelated CAD patients with positive coronary angiograms and 159 age matched control subjects without a history of symptomatic CAD. The eNOS gene intron4a/b VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. RESULTS: The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 68.8, 29.1 and 2.1 per cent in CAD subjects, and 81, 18.4 and 0.6 per cent in control subjects, respectively. The genotype frequencies differed significantly (P<0.05) between the two groups. The frequency of the a allele was 16.7 per cent in CAD subjects and 9.8 per cent in control subjects and was significantly higher in the patients (P<0.05, Odds ratio=1.84). Plasma lipids, except HDL-C were also significantly increased in CAD group. INTERPRETATION & CONCLUSION: Though the genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a, also 'a' allele frequency differed significantly between the CAD patients and controls, this polymorphism was not an independent risk factor for the development of CAD in Iranian patients. Further studies with larger samples need to be done to confirm these findings. PMID- 17287557 TI - Role of anti cyclic citrullinated peptide antibodies in erosive disease in patients with rheumatoid arthritis. AB - BACKGROUND & OBJECTIVES: Antibodies to cyclic citrullinated peptide (CCP) are a recently described marker in rheumatoid arthritis (RA), which are said to connote aggressive disease. No data on these antibodies are available from India. We undertook this study to evaluate the role of second generation anti CCP antibodies (anti CCP-2) in predicting erosive disease in Indian patients with rheumatoid arthritis and to define their role in seronegative RA. METHODS: A total of 211 patients with established RA were evaluated in this cross-sectional study for radiographic erosions. A high percentage of seronegative RA patients (40%) were included to assess the role of anti CCP-2 antibodies in this subgroup. Radiographic damage was quantified using modified Sharp score. Apart from anti CCP-2 antibodies, other factors evaluated for their ability to predict erosions included rheumatoid factor (RF) positivity, disease duration, and disease modifying anti rheumatic drugs (DMARD) naive period. RESULTS: Anti CCP-2 antibodies were seen in 80 per cent patients with RA. Predictors of erosive disease included anti CCP-2 antibody positivity and DMARD naive period. Patients positive for both RF and anti CCP-2 antibodies had a higher prevalence of erosions as compared to patients positive for only one antibody or negative for both. In seronegative RA (RF absent), anti CCP-2 antibodies were seen in over 50 per cent patients and were associated with a higher incidence of erosive disease. INTERPRETATION & CONCLUSION: Our finding showed that anti CCP-2 antibodies were present in 80 per cent patients with established RA. These have an independent role in predicting erosive disease, especially in the seronegative subgroup. PMID- 17287558 TI - Hypolactasia & lactose intolerance among three ethnic groups in Malaysia. AB - BACKGROUND & OBJECTIVES: Prevalence of adult-type hypolactasia is known to vary among different countries and in different ethnic populations in the same country. The present study was undertaken to evaluate the prevalence of hypolactasia and lactose intolerance in three different ethnic populations living in similar environmental conditions in Malaysia. The correlation between different symptoms and lactose intolerance test was also studied. METHODS: A total of 300 Malaysian subjects from three different ethnic populations: Malays, Chinese and Indians (100 volunteers in each group, 18-49 yr old working or studying in a University) were included. Urine galactose excretion and gastrointestinal symptoms were measured after lactose intake (50 g). RESULTS: Based on galactose excretion, 88 per cent of the Malays, 91 per cent of the Chinese and 83 per cent of the Indians were hypolactasic. The differences were statistically not significant. When the symptoms were also considered, prevalence of lactose intolerance appeared to be significantly lowest among the Indians. When the subjects were divided into low, middle and high galactose excretion groups some correlation was found between the symptoms and galactose excretion. INTERPRETATION & CONCLUSION: There was no clear association between hypolactasia and gastrointestinal symptoms in all the study groups. However, the lactose intolerance was high in all the study groups indicating the increasing demand for low lactose dairy products in the Asian countries. PMID- 17287559 TI - Prevention of opportunistic infections in HIV infection by pentoxiphylline. AB - BACKGROUND & OBJECTIVES: Levels of tumour necrosis factor (TNF) are increased in patients with HIV infection leading to increased apoptosis and reduced CD4 cell life. Pentoxiphylline is a TNF inhibitor with properties that might make it useful for the treatment of HIV infection. These include improved cell mediated immunity and inhibition of viral replication. We carried out this study to determine the therapeutic utility of pentoxiphylline in improving constitutional manifestations, preventing opportunistic infections and sustaining CD4 counts among asymptomatic HIV infected individuals (i.e., those with no opportunistic infection). METHODS: Individuals with HIV infection who were over 18 yr of age and free of opportunistic infections were recruited in the study and followed up 4 weekly. CD4 counts were measured using a flowcytometer using anti-human CD4 intervals. Pentoxiphylline was prescribed in a dose of 400 mg thrice daily. RESULTS: Thirty three (18 males) patients with HIV infection were studied. During their follow up (mean 12.5 +/- 5.6 months) one patient each developed cryptococcal meningitis and fibrocavitary tuberculosis. Weight increased from 51.3 +/- 7.4 kg at baseline to 55.3 +/- 7.4 kg (P<0.05). Malaise, fatigue and appetite improved in all those with these complaints, except the two with opportunistic infections. Mean CD4 counts were 184 +/- 36.4/microl at baseline and increased to 210 +/- 28.6/microl3 at four weeks (P<0.05). The patients had stable CD4 counts over the follow up period since then, i.e., within 25 per cent of the previous levels. INTERPRETATION & CONCLUSION: Pentoxiphylline therapy in HIV infected individuals, who were free of opportunistic infections, improved their body weight, minimized opportunistic infections, increased and sustained CD4 counts. Given the low cost of the drug it could be recommended for the use in individuals who are at a high risk of developing opportunistic infections. PMID- 17287560 TI - The role of allopurinol in experimental acute necrotizing pancreatitis. AB - BACKGROUND & OBJECTIVES: Acute pancreatitis (AP) in its severe form can lead to severe complications and death. Translocation of bacteria from the gut is one of the most important factors in the development of septic complications and mortality in acute pancreatitis. Oxygen-derived free radicals have been suggested to play a major role in the pathogenesis of AP. Xanthine oxidase enzyme is an important source of reactive oxygen metabolites. We undertook this study to evaluate the effect of allopurinol on bacterial translocation, oxidative stress and the course of AP in a rat model. METHODS: Male Sprague-Dawley rats (n=48) were randomly allocated into three equal groups. Acute pancreatitis (AP) was induced in group II (AP+Saline), and group III (AP+allopurinol) by retrograde infusion of taurocholate into the common biliopancreatic duct. Group I rats (Sham) received normal saline infusion into the common biliopancreatic duct for mimicking pressure effect. Group III rats were treated with allopurinol intraperitoneally for 48 h after induction of pancreatitis. Blood samples were drawn from all animals for biochemical analyses and pancreatic tissues were examined for bacterial translocation. RESULTS: Acute pancreatitis was developed in all groups, but not in group I (Sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Pathologic score of the pancreatitis in the allopurinol group (14.0 +/- 0.5) was lower when compared with group II (19.2 +/- 0.6) (P<0.001). Bacterial translocation to pancreas in group treated with allopurinol was significantly lower when compared with control group (p<0.02). Plasma glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were higher and malondialdehyde (MDA) levels were lower in allopurinol group when compared with those in control groups. INTERPRETATION & CONCLUSION: Our findings suggested that addition of allopurinol to the treatment protocol in the acute pancreatitis might improve the pathologic score, bacterial translocation and oxidative stress parameters. However, more studies need to be done to confirm these findings. PMID- 17287561 TI - Synergistic effect of alcohol & fructose administration on blood urate & biochemical indices of insulin resistance in albino rabbits. PMID- 17287562 TI - Seroepidemiology of a focal outbreak of dengue in Tamil Nadu. PMID- 17287563 TI - [Physiological function of arginine and its metabolites in plants]. AB - L-arginine is an important and unique amino acid in plants. It serves not only as an important nitrogen reserve and recycling, but also as a precursor of the biosynthesis of polyamines, nitric oxide and so on. Polyamines and nitric oxide are important messengers involved in almost all physiological and biochemical processes, growth & development, and adaptation of plants to stress. Arginine decarboxylase, arginase and nitric oxide synthase are the key enzymes in L arginine catabolism, in which polyamines are formed through ADC or arginase-ODC pathway while nitric oxide is formed through the NOS pathway. The relative activity of these three enzymes can control the direction of arginine metabolism. Arginine content keeps higher level in roots during overwinter period. The arginine metabolism plays important role in perception and adaptation of plant to environmental disturbances. PMID- 17287564 TI - [Dehydration-induced intracellular solute changes and acquisition of plant desiccation tolerance]. AB - Some desiccation-tolerant plants can survive the loss of water even when the water content becomes as low as 0.3 g H2O/g dry weight, and can still repair quickly their cellular structures and function damages by desiccation when they get access to enough moisture again. While moderate dehydration, the tissue could accumulate some special proteins, small molecules, carbohydrate etc. which can protect the original structure and function of macromolecule and membrane through themselves' natural characteristics. Mean-while, water loss results in increased activities of reactive-oxygen-scavenging enzymes (SOD, CAT, APX and GR). For the acquisition of desiccation tolerance, water in the plants or seeds must be induced to enter the glassy state, a change which can be induced by many compounds. The crucial protective means also include the increased formation of endogenous antioxidants and the partitioning of amphiphilic substances in the lipid phase to protect the membrane. The resurrection plants and seeds are good materials for desiccation tolerance research. PMID- 17287565 TI - Changes in proteins within germinating seeds of transgenic wheat with an antisense construct directed against the thioredoxin. AB - Thioredoxin h is closely related to germination of cereal seeds. The mechanism of transgenic wheat seeds with antisense trxs gene, which is responsible for low germination rate was studied through analyzing the changes in proteins of wheat seeds during germination. The antisense trxs could weaken the metabolism of wheat seeds by decreasing the quantity of proteins involved in metabolism, while chloroform-methanol (CM) protein fraction consisted mostly of some low molecular weight proteins (<20 kD). Compared with wild-type wheat seeds, the folding of glutenin in transgenic wheat ones was affected during the wheat maturating. Big glutenin macropolymers could be formed more easily in transgenic wheat seeds than in wild-type wheat ones. Therefore, the degradation speed of glutenin in transgenic wheat seeds was slower than that in wild-type wheat ones during seed germination. In addition, the degradation of some proteins in transgenic wheat embryos was also delayed during germination. PMID- 17287566 TI - Comparison of starch synthesis and related enzyme activities in developing grains among different types of maize. AB - The relationships between the rates of starch synthesis and the activities of enzymes responsible for starch biosynthesis in developing grains of normal, pop, sweet and waxy corns were investigated and compared throughout the grain filling period. The results indicated that the rates of starch synthesis and the activities of sucrose synthase (SS), soluble starch synthase (SSS), granule-bound starch synthase (GBSS), starch-branching enzyme (SBE) and starch-debranching enzyme (DBE) each exhibited a single peak during grain filling period. Normal corn showed significantly higher SS activity than other genotypes between 30 and 40 DAP. The mean and maximum activities of SSS were in the following order: normal corn>waxy corn>pop corn>sweet corn. GBSS activities were significantly higher in normal corn, and significantly lower in waxy corn at late filling period. SBE activity of waxy corn was significantly higher than other lines after 10 DAP. DBE activity of sweet corn was extremely low and completely lost at 40 DAP. The rates of starch synthesis had some correlation with the activities of SS, SSS, GBSS and SBE during the grain filling process. No correlation was found between the rates of starch synthesis and the activities of ADP-glucose pyrophosphorylase (AGPase) and DBE. SS activity appears to play a major role in starch biosynthesis in maize. GBSS is responsible for amylose synthesis especially in the later period. SSS and SBE are associated with amylopectin biosynthesis. PMID- 17287567 TI - Histological observation of somatic embryogenesis from cultured embryos of Quercus variabilis Bl. AB - Immature zygotic embryos of Quercus variabilis Bl. were excised and cultured on MS basal medium containing 0.25 mg/L 2,4-dichlorophenoxyacetic acid and 0.5 mg/L 6-benzyl aminopurine. Callus was initiated from these embryos within 6 weeks. Two types of embryogenic calluses were formed: one was the white mucilaginous callus and the other was light yellow to translucent, glossy, mucilaginous. Histological examination showed that the non-embryogenic cells derived from zygotic embryos were large in size, with small nuclei, thin cytoplasm, and the embryogenic cells were small in size, with large nuclei, thick cytoplasm and denser arrangement. Somatic embryos were induced from embryogenic masses (EMS) cultured on a medium not containing plant growth regulators (PGRs). The histological origin of somatic embryos was single epidermal or subepidermal cells. Somatic embryos displayed a standard development pattern, from globular ones to heart-like and torpedo-shaped ones and finally to embryo with two cotyledons, which was similar to the development of zygotic embryo in vivo. Secondary proembryos were formed on the axis and cotyledon of existing embryos and originated from single, densely stained cells of the epidermis at all stages. PMID- 17287568 TI - Stimulatory effect of phytosulfokine-alpha on the proliferation of tobacco 'Bright Yellow 2' suspension cells. AB - 'Bright Yellow 2' ('BY-2') tobacco (Nicotiana tabacum L.) suspension cells could not proliferate even with proper 2, 4-D concentration (0.6 mg/L) in the medium, when the initial cell density is low. However, the cells could divide and grow normally if conditioned medium (CM) was added to the medium, and the rate of proliferation of cells was proportional to the quantities of CM supplied. The same results were obtained, when the CM was replaced by synthesized phytosulfokine-alpha (PSK-alpha), a sulfated pentapeptide, PSK-alpha was found in CM of 'BY-2' cells by MS identification. From the significant linear relationship between rate of cell proliferation (measured by OD600 value) and concentrations (0.05 nmol/L-10 micromol/L) of PSK-alpha, it can be seen that the 'BY-2' suspended cells are the ideal plant material for bioassay of PSK-alpha. This result suggests that the PSK-alpha might be involved in promoting the proliferation of 'BY-2' suspension cells. PMID- 17287569 TI - [Relationship between chloride tolerance and polyamine accumulation in Glycine max, Glycine soja, and their hybrid seedlings]. AB - The seedlings of the F4 hybrid strain 'JB185' selected for salt tolerance generation by generation, their parents Glycine max cv. Jackson and Glycine soja population 'BB52' were treated with different NaCl concentrations and iso-osmotic (-0.53 MPa) PEG-6000, NaCl, Na+ (without Cl-) and Cl- (without Na+) solutions for 6 d. The results showed that: (1) The relative electrolyte leakage and malondialdehyde (MDA) content in leaves of the above three soybean seedlings showed an increase trend when the NaCl concentration was elevated, but chlorophyll contents decreased except the significant increase in 'BB52' and 'JB185' under NaCl 50 mmol/L stress. The change in 'JB185' was between its parents. (2) Under different iso-osmotic stresses, the relative electrolyte leakage and MDA contents in leaves of three soybean seedlings also increased mostly, the changes in 'BB52' and 'JB185' under Na+ (without Cl-) stress were more than those under Cl- (without Na+) stress. The free and bound Put, Spd and Spm contents in leaves all increased when compared with the control, the ratios of free (Spd+Spm)/Put and total bound polyamines in 'BB52' and 'JB185' seedlings under Na+ (without Cl-) treatment were the lowest one among three iso-osmotic salt stresses. The results indicate that the F4 hybrid strain 'JB185' is more sensitive to Na+ than Cl- as its wild parent 'BB52' population. PMID- 17287570 TI - Effects of iron deficiency on photosynthesis and photosystem II function in soybean leaf. AB - Gas exchange and chlorophyll a fluorescence in soybean plants were investigated to explore the effects of iron deficiency on photosynthesis and photosystem II function in vivo. Iron deficiency induced a drastic decrease in net photosynthesis (Pn). Compared with normal plants, the maximal quantum yield of PSII photochemistry (psipo) in iron-deficient plants was only slightly lower; whereas, the efficiency with which a trapped exciton can move an electron into the electron transport chain further than QA-(Psio) and quantum yield of electron transport beyond QA (psiEo) were significantly depressed. Iron deficiency also caused a clear enhancement of the relative variable fluorescence at K step (VK). When exposed to light, iron-deficient plants had considerably lower efficiency of excitation energy capture by open PSII reaction centers (Fv'/Fm'), quantum yield of PSII electron transport (PhiPSII), and photochemical quenching coefficient (qP), but markedly higher non-photochemical quenching (NPQ). In addition, post illumination transient increase in chlorophyll fluorescence was clearly enhanced in iron-deficient plants. Basing on these data, we suggest that both the donor and the acceptor sides of PSII complex were damaged by iron deficiency; cyclic electron transport around PSI in iron-deficient soybean plants might play an important role in inducing the excitation energy dissipation and meeting the demand for extra ATP as a compensation for the loss of phosphorylation capability. PMID- 17287571 TI - Molecular identification of two new self-incompatible alleles (S-alleles) in Chinese pear (Pyrus bretschneideri). AB - Self-incompatibility (SI) is an important intraspecific reproductive barrier in flowering plants. To identify the S-alleles of Chinese pear species (Pyrus pyrifolia, P. bretschneideri, P. ussuriensis and P. sinkiangenis etc.), S-RNase specific PCR amplification, sequence analyses and field pollination tests were performed using two cultivars 'Jingxiang' and 'Esu' of P. bretschneideri as materials. Two new S-RNase genes were identified from the two cultivars. They were 1,122 bp and 1,058 bp in length, and designated as S37-RNase (GenBank accession no. DQ839238) and S38-RNase (GenBank accession no. DQ839239). By comparison of their deduced amino acid sequences with those of S1-to S36-alleles of Oriental pear, it can be seen that both the two new S-alleles had their conserved regions C1 and C2, but their hypervariable regions (HV) were quite different from those of the others. S37 showed a higher similarity (96%) to S38 in the amino acid sequences deduced from them, whereas both of them displayed the highest similarity (98%) to S15 and the lowest (63%) to S32. The two S-alleles had introns of 786 bp and 723 bp, respectively, similar in size to that of S15 (777 bp). Finally, the S-genotypes of 'Jinxiang' and 'Esu' were unambiguously determined as S34S37 and S15S38, respectively. PMID- 17287572 TI - [Construction and preliminary analysis of subtractive library for peel pitting of 'Fengjie' navel orange fruit]. AB - In this study, the pitted peel and non-pitted peel of 'Fengjie' navel orange fruits were used as experimental materials to construct and screen the peel pitting related genes by suppression subtractive hybridization (SSH). The results showed that suppression subtractive hybridization was very effective. A cDNA library of differentially expressed genes was constructed. The library included about 200 clones with an average insert size of around 300 bp. Part of the positive clones were picked up randomly and sequenced. Six of the 50 clones had no homologous sequences being found and three had unknown functions in GenBank. According to the analysis of the homology, four homologous (Ca2+ binding protein, cysteine proteinase, NAC-domain protein and expansin) genes were chosen to examine their expressions through semi-quantitative RT-PCR analysis in pitted and non-pitted navel orange fruits. The expression of four genes were all higher in pitted peel than that in non-pitted peel. It suggests that these genes in the SSH cDNA library may be involved with peel pitting and can be subject of future investigation to explore the molecular biological mechanism of the pitting of citrus fruit. PMID- 17287573 TI - [An analysis of genetic diversity of different ecotypes of reed (Phragmites communis Trin.) by molecular marker techniques]. AB - ISSR (inter-simple sequence repeat) and RAPD (random-amplified polymorphic DNA) markers were used to detect genetic diversity of 4 different ecotypes of reed (Phragmites communis Trin.) growing in Hexi Corridor, Gansu province. Nine effective primers were screened from 30 ISSR arbitrary primers, and a total of 99 DNA bands were amplified, among which 51 (51.5%) were polymorphic. Thirteen effective primers were screened from 45 RAPD 10-oligonucleotide arbitrary primers, and a total of 195 DNA bands were amplified, among which 87 (44.6%) were polymorphic. Genetic identity based on ISSR and RAPD data showed a positive correlation (r=0.845, P<0.05). Based on unweighted pair-group method with arithmetic averages (UPGMA) cluster analysis on DNA bands amplified, together with the correlation analysis between genetic distance and soil water contents and soluble salt contents as well, the present results suggest that the genetic diversity occurs among the four ecotypes of reed in adaptation to long term natural drought and salinity, showing an obvious evolutional tendency from swamp reed via salt meadow reed to dune reed. PMID- 17287574 TI - Sequential amplification of flanking sequences by Y-shaped adaptor dependent extension using multiple templates. AB - Y-shaped adaptor dependent extension (YADE) method is a useful tool to amplify the flanking sequence of a known DNA sequence, but its efficiency is frequently limited by the restriction sites around the known sequence. In this paper, we demonstrated that using multiple templates derived from several restrictions and ligations could dramatically increase the efficiency of YADE method and render it suitable for sequential amplification of flanking sequences. With templates originating from 7 digestions, a 2,228-bp 5'-upstream sequence of a cotton small GTPase gene was obtained by two rounds of sequential YADE amplifications. The results demonstrated that the YADE method with multiple templates may be a useful tool for sequential PCR walking in complex genomes. PMID- 17287575 TI - Development of fungiform papillae: patterned lingual gustatory organs. AB - The fungiform papilla is a gustatory organ that provides a specific tissue residence for taste buds on the anterior tongue. Thus, during development there must be a progressive differentiation to acquire papilla epithelium, then taste cell progenitor epithelium, and finally taste cells within the papilla apex. Arranged in rows, the patterned distribution of fungiform papillae requires molecular regulation not only to induce papillae, but also to suppress papilla formation in the between-papilla tissue. Intact sensory innervation is not required to initiate papilla development or pattern. However, members of several molecular families have now been identified with specific localization in developing papillae. These may participate in papilla development and pattern formation, and subsequently in taste progenitor and taste cell differentiation. This review focuses on development of fungiform papillae in embryonic rat and mouse. Basic morphology, cell biology and molecular phenotypes of developing papillae are reviewed. Regulatory roles for molecules in several families are presented, and a broad schema is proposed for progressive epithelial differentiation to form taste cell progenitors in parallel with the temporal course, and participation of lingual sensory innervation. PMID- 17287576 TI - Cell lineage and differentiation in taste buds. AB - Mammalian taste buds are maintained through continuous cell renewal so that taste bud cells are constantly generated from progenitor cells throughout life. Taste bud cells are composed of basal cells and elongated cells. Elongated cells are derived from basal cells and contain taste receptor cells (TRC). Morphologically, elongated cells consist of three distinct types of cells: Types I, II and III. In contrast to the remarkable progress in understanding of the molecular basis for taste reception, the mechanisms of taste bud maintenance have remained a major area of inquiry. In this article, we review the expression of regulatory genes in taste buds and their involvement in taste bud cell differentiation. Three major topics include: 1) the Sonic hedgehog (Shh)-expressing cell in the basal cell in taste buds as a transient precursor of elongated cells and as a signal center for the proliferation of progenitor cells; 2) the Mash1-expressing cell as an immature cell state of both Type II and Type III cells and as a mature cell state of Type III cell; and 3) the nerve dependency of gene expression in taste buds. Problems in the application of NCAM for the type III cell marker are also discussed. PMID- 17287577 TI - Acid-sensing ion channels in taste buds. AB - Taste receptor cells detect gustatory stimuli using a complex arrangement of ion channels, G protein-coupled receptors, and signaling cascades. Sour and salty tastes are detected by ion channels in the rat. Using a combination of homology screening and functional expression approaches, we screened a rat circumvallate papilla cDNA library and identified acid-sensing ion channel-2a (ASIC2a) and ASIC2b as candidates for the rat sour-sensing channels. In situ hybridization and reverse transcription-polymerase chain reaction experiments revealed that ASIC2a and ASIC2b transcripts were localized in taste bud cells. Immunohistochemistry and immunoprecipitation also revealed that both subunits were expressed in a subset of taste cells and that some of the cells expressed ASIC2a/ASIC2b heteromeric assemblies. Electrophysiological studies demonstrated that stimulation of acetic acid produced larger ASIC2 currents than did hydrochloric acid at the same pH. ASIC2a/ ASIC2b channels generated maximal inward currents at pH Mn2+, Ni2+ in normal Ca2+ solution. In contrast, the frequency of I(sc) was unchanged over the range of concentrations of the Ca2+ channel antagonists used. Our results show that the oscillatory I(sc) evoked by Ba2+ involves L-type voltage gated Ca2+ channels. We conclude that L-type Ca2+ channels play a key role in the oscillation at the neuroepithelial junctions of guinea pig colon. PMID- 17287600 TI - Neuroendocrine system response modulates oxidative cellular damage in burn patients. AB - Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn. PMID- 17287601 TI - Contamination of the Shinano River water with mutagenic substances after the Niigata Chuetsu Earthquake. AB - While normally monitoring the Shinano River water quality, including examinations for mutagenicity, the Niigata Chuetsu Earthquake suddenly occurred on October 23, 2004. However, the influence of this earthquake on the mutagenicity of river water has not yet been well studied. To clarify the regional and seasonal changes in mutagenicity of the Shinano River water, blue rayon was suspended for 24 hrs at 4 sampling sites, once a month from September 2004 through August 2005. Mutagenicity was evaluated by the Ames test using Salmonella typhimurium TA98 (TA98) and TA100 with or without metabolic activation by S9 mixture. To detect and identify poly-aromatic hydrocarbons that may be responsible for the mutagenicity of the river water, we analyzed benzo[a]pyrene, benzophenone, 4 nitrotoluene, or other compounds using gas chromatography-mass spectrometry and total ion chromatogram spectra. Positive manifestations of TA98 with S9 mixture were observed at the 4 sampling sites throughout the 12-month test, showing a tendency to be higher at the downstream site and in winter. However, the highest mutagenicity was observed in the sample collected at the most upstream sampling site in December 2004, and fluoranthene or pyrene consisting mainly in coal tar was detected only in the samples collected in December 2004. Although benzo[a]pyrene, benzophenone, and 4-nitrotoluene were below the detection limits, non-mutagens such as aliphatic hydrocarbons or esters were frequently detected. Our findings indicate that either fluoranthene or pyrene was mainly responsible for the mutagenicity of the river water in December 2004, suggesting the possibility of oil contamination caused by the Niigata Chuetsu Earthquake. PMID- 17287602 TI - Treatment with unsaponifiable extracts of avocado and soybean increases TGF-beta1 and TGF-beta2 levels in canine joint fluid. AB - Avocado and soya unsaponifiables (ASU) are plant extracts used as a slow-acting antiarthritic agent. ASU stimulate the synthesis of matrix components by chondrocytes, probably by increasing the production of transforming growth factor beta (TGF-beta). TGF-beta is expressed by chondrocytes and osteoblasts and is present in cartilage matrix. This study investigates the effect of ASU treatment on the levels of two isoforms of TGFbeta, TGF-beta1 and TGF-beta2, in the knee joint fluid using a canine model. Twenty-four outbred dogs were divided into three groups. The control animals were given a normal diet, while the treated animals were given 300 mg ASU every three days or every day. Joint fluid samples were obtained prior to treatment, and at the end of every month (up to three months). TGF-beta1 and TGF-beta2 levels were measured using a quantitative sandwich enzyme immunoassay technique. ASU treatment caused an increase in TGF beta1 and TGF-beta2 levels in the joint fluid when compared to controls. The different doses did not cause a significant difference in joint fluid TGF levels. TGF-beta1 levels in the treated animals reached maximum values at the end of the second month and then decreased after the third month, while TGF-beta2 levels showed a marginal increase during the first two months, followed by a marked increase at the end of the third month. In conclusion, ASU increased both TGF beta1 and TGF-beta2 levels in knee joint fluid. PMID- 17287603 TI - Nicotine potentiates the electrical field stimulation-evoked contraction of non pregnant rabbit myometrium. AB - The women who smoke have lower fertility rates which might be due to harmful effects of nicotine on tubal function and menstrual cycle. Although the uterine contractility of the non-pregnant uterus plays an important role in the human reproduction process, the influence of nicotine on the contractile responses in uterus is not known. Nicotine increases the release of neurotransmitters following nerve stimulation both in the central and peripheral nervous system through acting on nicotinic acetylcholine receptors (nAchRs). The aim of this study was to examine whether the electrical field stimulation (EFS)-evoked contraction is altered in rabbit myometrium strips in the presence of nicotine to evaluate the changes in contractility. EFS-evoked contractile responses were recorded from myometrium strips obtained from non-pregnant rabbits in the absence and presence of nicotine. Nicotine led to the increase in the amplitudes of the EFS-evoked contractile responses in a dose-dependent manner. Therefore, the effects of hexamethonium, cadmium, indomethacin, atropine, and N(omega)-Nitro-L arginine methyl ester hydrochloride were tested on the EFS-evoked contractions in the absence or presence of nicotine to clarify the mechanisms of nicotine-induced potentiation in EFS-evoked contractile responses. Indomethacin, a non-selective cyclooxygenase inhibitor, and hexamethonium, a ganglionic blocker, inhibited nicotine-induced increase in EFS-evoked responses, whereas other chemicals produced no effect. These results suggest that nicotine-induced potentiation may be mediated by nAchRs and prostaglandins. In conclusion, failure of quiescence in the uterus due to increased contractility by nicotine might be one of the factors contributing to infertility in female smokers. PMID- 17287604 TI - Steroid-resistant late acute rejection after a living donor liver transplantation: case report and review of the literature. AB - The majority of acute cellular rejection occurs in the first few months after liver transplantation. It has been, however, reported that some recipients experience late acute rejection, which occurs more than 3 months after transplantation. We herein report a case of late acute rejection that occurred nearly 10 years after liver transplantation. The patient is a 27-year-old male who underwent a living donor liver transplantation when he was 17 years old. At 9 years 6 months after transplantation, the patient presented with the elevated serum levels of liver enzymes and total bilirubin. A liver biopsy showed acute cellular rejection. Steroid bolus therapy was not effective, but we successfully used deoxyspergualin as a rescue therapy. Late acute cellular rejection that occurs nearly 10 years after transplantation has so far been rarely reported. It is generally believed that late acute rejection may be more resistant to treatment and be associated with a higher rate of graft loss, as well being associated with the development of chronic ductopenic rejection. In this report, we have shown that deoxyspergualin is safe and effective for treatment of steroid resistant late acute rejection, preventing from graft loss of chronic rejection. PMID- 17287605 TI - ADA*2 allele of the adenosine deaminase gene may protect against coronary artery disease. AB - BACKGROUND/AIMS: The common G22A polymorphism in the adenosine deaminase (ADA) gene leads to substitution Asp8Asn. The lower activity of the enzyme encoded by A22 (ADA*2) allele may increase tissue concentrations of adenosine, a potent cardioprotective agent. In a case-control study, we investigated the association between ADA polymorphism and coronary artery disease (CAD). METHODS: A hundred and seventy-one CAD patients from the north-western part of Poland and 200 consecutive newborns from the same population were genotyped by PCR-RFLP. RESULTS: Twenty-five ADA*1/*2 heterozygotes (12.5%) and 2 ADA*2/*2 homozygotes (1%) were found in the control group, while only 10 *1/*2 heterozygotes (5.9%) and no *2/*2 homozygotes were found in the CAD group. Frequencies of ADA*2 carriers (5.9% vs. 13.5%, p = 0.015) and ADA*2 allele (2.9% vs. 7.3%, p = 0.0083) were lower in CAD patients than in controls. Among CAD patients, a significantly lower proportion of *2 allele carriers was treated with diuretics and ACE inhibitors when compared to *1/*1 wild-type homozygotes. CONCLUSION: ADA*2 allele may decrease genetic susceptibility to CAD. ADA should be added to the list of candidate genes modifying the risk of cardiovascular diseases. PMID- 17287606 TI - Quality of life in women with urinary stress incontinence and evaluation of tension-free vaginal tape treatment. AB - OBJECTIVES: Assessment of quality of life in women stress urinary incontinence (USI) and evaluation of tension-free vaginal tape (TVT) treatment. MATERIAL AND METHODS: The research included a group of 112 women aged 33-78 years. Before as well as 3 and 6 months after the TVT operation, patients were asked to fill in quality of life questionnaires. RESULTS: After 3 months 87.25% of the women reported full regression of USI symptoms, 7.8% an insignificant improvement, and 4.9% did not observe any change. After 6 months 85.71% reported full regression, 9.18% an insignificant improvement, and 5.1% did not observe any change. USI is responsible for a decrease in physical activity. The most uncomfortable symptom is involuntary urine leakage occurring mainly during an effort or sleep. After the TVT procedure, the majority of women confirmed a significant improvement in quality of life. CONCLUSIONS: The TVT procedure is an effective method of treating USI in women: it significantly improves quality of life, with a recovery rate of 85-87%, and a low rate of complications. PMID- 17287607 TI - Detection of Mycobacterium leprae in ocular tissues by histopathology and real time polymerase chain reaction. AB - AIM: To report detection of leprosy in ocular tissue by histopathology and its confirmation by genetic analysis. METHODS: Excised tissue from a clinically suspected ocular leprosy patient was processed and analyzed histopathologically. The DNA from the paraffin-embedded tissue was extracted, an 85 A-C intergenic region of Mycobacterium leprae was amplified using specific primers and analyzed by conventional as well as real-time polymerase chain reaction (RT-PCR). RESULTS: With periodic acid-Schiff-hematoxylin (PAS-H) staining the specimen showed presence of a thin fibrinous layer of inflammatory cells. The majority of the tissue was fibrovascular with extensive infiltration by histiocytes having reticulated cytoplasm. Modified PAS-H and acid-fast staining (AFS) showed the presence of several acid-fast organisms within the cytoplasm of histiocytes and mast cells. Conventional PCR showed a 250-bp DNA from excised conjunctival tissue, which was in agreement with the positive controls for M. leprae. Through RT-PCR, it was calculated that the suspected tissue had 44.68 pg of M. leprae DNA, which is 8937.06 genome copies of M. leprae. CONCLUSIONS: Presence of inflammatory cells and AFS bacilli in tissue presented a typical picture of leprosy. M. leprae DNA can be detected using RT-PCR in ocular tissues when acid fast bacteria are seen in histopathological sections. And when the diagnosis of leprosy is inconclusive and acid-fast bacteria are seen, RT-PCR for M. leprae DNA could be used as a rapid confirmatory test to identify the presence of M. leprae and, therefore, the diagnosis of leprosy. PMID- 17287608 TI - A suggestive association of fuchs heterochromic cyclitis with cytotoxic T cell antigen 4 gene polymorphism. AB - BACKGROUND: Fuchs heterochromic cyclitis (FHC) is a chronic inflammatory eye disease, usually presenting as unilateral anterior uveitis. Up to date no disease susceptibility genes have been described for FHC. METHODS: The allele frequency of HLA DRB1 and DQB1, polymorphisms of the tumour necrosis factor (TNF) alpha promoter region (-376, -308, -238), the promoter (-318), first exon (+49) and (AT)n repeat polymorphism of the cytotoxic T cell antigen 4 (CTLA4) gene were analysed in 44 FHC patients and 139 healthy controls. RESULTS: The CTLA4 -318 C/T genotype was increased in FHC patients [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.4-6.5], as well as long CTLA4 (AT)n microsatellite alleles with more than 16 AT repeats (OR 2.6, 95% CI 1.3-5.3). A trend towards the -308 G/A TNF-alpha genotype was found in the patient cohort, whereas no difference in HLA class II allele distribution was observed. CONCLUSION: CTLA4 but not TNF-alpha or HLA class II DRB1 and DQB1 may represent a candidate gene for disease susceptibility in FHC. PMID- 17287609 TI - Academic skills: focusing. PMID- 17287611 TI - Production and Characterization of Monoclonal Antibodies for Immunoassay of the Lung Cancer Marker proGRP. AB - Progastrin-releasing peptide (proGRP) is a precursor of gastrin-releasing peptide, a hormone which is secreted from neuroendocrine cells. It has been shown to be a useful serum marker for small cell lung cancer. We raised monoclonal antibodies (MAbs) against proGRP with the primary aim of establishing a sensitive immunoassay. Immunization was performed with recombinant proGRP (amino acids 31 98) conjugated to thyroglobulin or with a DNP-modified peptide. Seven of the MAbs recognizing both recombinant and cell line-derived peptide were characterized and epitope-mapped. Based on cross-inhibition studies the antibodies could be categorized into three main groups. The molecular epitope assignment was studied by using phages displaying proGRP peptides, random peptide libraries displayed on phage and by pepscan analysis utilizing 10-mer biotinylated peptides. Two of the MAbs (E146, E172) bound to a defined region on the N-terminal part of proGRP(31 98), three recognized conformational-dependent epitopes in the middle of the peptide (E179, E180, E181) and two bound to the C-terminal part (E149, E168). Consensus sequences were obtained for MAbs E146, E149 and E168. The binding kinetics of the MAbs was determined by surface plasmon resonance, and a time resolved immunofluorometric assay was established. PMID- 17287612 TI - Induction of apoptosis signal-regulating Kinase 1 by E2F-1 may not be essential for E2F-1-mediated apoptosis in melanoma cells. AB - OBJECTIVES: In the present study, we investigate the role of apoptosis signal regulating kinase 1 (ASK1) mitogen-activated protein (MAP) kinase signal pathways in E2F-1-mediated apoptosis. METHODS: A gene expression profile in response to E2F-1 overexpression was performed by cDNA microarray analysis and confirmed by real-time reverse-transcription polymerase chain reaction. Kinase activities were assayed by Western blot analysis or kinase assay. Apoptosis was assessed by morphologic inspection and flow-cytometric analysis. Cytotoxicity was monitored by MTT assay. RESULTS: E2F-1 upregulated the expression of ASK1 8-fold compared to the Ad-LacZ-infected control in SK-MEL-2 melanoma cells, which was confirmed by reverse-transcription polymerase chain reaction. Sequence analysis showed that there are 2 putative E2F-1 DNA binding sites in the ASK1 promoter region. Truncated E2F-1 protein, which lacks the transactivation domain, failed to upregulate ASK1, suggesting that ASK1 was regulated at the transcriptional level by E2F-1. E2F-1 overexpression resulted in the transient activation of c-Jun N terminal kinase (JNK); however, dominant negative mutant ASK1 had no effect on E2F-1 cytotoxicity and JNK activation. p38 was not activated by E2F-1, and inhibition of p38 had no effect on E2F-1-mediated cell death. The ASK1 kinase assay showed that ASK1 activity was not upregulated in response to E2F1 overexpression. The inhibition of ASK1 upstream kinase-AKT can enhance E2F-1 mediated cell death. Moreover, an adenovirus expressing truncated E2F-1 keeps the ability of inducing apoptosis in melanoma cells. CONCLUSIONS: ASK1 expression is upregulated by E2F-1 at the transcription level, but the upregulation of ASK1 expression by E2F-1 was not coordinated with an increased ASK1 activity. The ASK1 JNK/p38 pathway does not appear to play a crucial role in E2F-1-induced apoptosis. PMID- 17287617 TI - Burns or pressure ulcers in the surgical patient? 1988. PMID- 17287618 TI - The NPUAP: look who else is turning 20! PMID- 17287620 TI - An update on wound care in Mexico. PMID- 17287621 TI - The edge effect: current therapeutic options to advance the wound edge. PMID- 17287623 TI - Does heart failure etiology, New York Heart Association class, or ejection fraction affect the ability of clopidogrel to inhibit heightened platelet activity? AB - The ability of clopidogrel to inhibit platelet function in patients with congestive heart failure (CHF) was proved by the PLUTO-CHF trial. We retrospectively analyzed platelet characteristics with respect to CHF etiology, class, and ejection fraction in patients enrolled in the PLUTO-CHF study. Twenty five patients were divided by CHF etiology, severity, and ejection fraction. All patients received aspirin 325 mg for at least 1 month prior to screening. Platelet function studies were performed at baseline and after 30 days of therapy. There were no differences in platelet parameters dependent on clinical characteristics of CHF, except for a significant (P = 0.023) decrease in platelet/endothelial cell adhesion molecule 1 (PECAM-1) expression in the New York Heart Association class III-IV due to the higher baseline values. Therapy with clopidogrel resulted in a significant inhibition of platelet activity assessed by ADP-induced and epinephrine-induced aggregation, closure time, expression of PECAM-1, glycoprotein Ib, glycoprotein IIb/IIIa antigen, glycoprotein IIb/IIIa activity with PAC-1, CD151, and reduced formation of platelet-leukocyte conjugates when compared with baseline. Clopidogrel provides antiplatelet protection in the broad spectrum of patients with CHF independently of its etiology, severity, or myocardial contractility. This uniform platelet inhibition with clopidogrel may be an important consideration in designing future large-scale clinical trials. PMID- 17287624 TI - Differential effects of direct thrombin inhibitors and antithrombin-dependent anticoagulants on the dynamics of clot formation. AB - New anticoagulants, including the direct thrombin inhibitors (DTIs) and fondaparinux, are increasingly replacing unfractionated heparin and enoxaparin. We examined the effects of argatroban (n = 60), bivalirudin (n = 44), heparin (n = 14), enoxaparin (n = 22), and fondaparinux (n = 24) on clot formation utilizing thromboelastography. Blood samples containing anticoagulants at clinically relevant concentrations were prepared ex vivo and analyzed using kaolin or tissue factor activation. Thromboelastography parameters of clot initiation (R), clot propagation (K and angle), clot rigidity (maximum amplitude) and clot elasticity (G) were compared between anticoagulants. Thromboelastography was also performed on blood from eight patients receiving anticoagulants. Each anticoagulant exerted significant concentration-dependent effects on R, K and angle. Only heparin, enoxaparin, and fondaparinux significantly affected maximum amplitude and G. Significant differences existed for all parameters between heparin and each anticoagulant and between fondaparinux and each DTI (P < 0.001), and for angle, maximum amplitude, and G between enoxaparin and each DTI (P < 0.008). Thromboelastography responses in ex-vivo samples and patient samples were comparable. In conclusion, whereas argatroban, bivalirudin, heparin, enoxaparin and fondaparinux each delay clot formation, the DTIs do not alter clot rigidity or elasticity. The reduced bleeding reported with DTIs versus heparin may relate to the fact that clots form with normal rigidity and elasticity. PMID- 17287625 TI - Influence of coagulation factors on extrinsic thrombin generation. AB - The extrinsic coagulation activity assay (EXCA) is a new thrombin generation test for the tissue factor pathway of coagulation. The EXCA was performed with 10 parts citrated plasma of different contents of fibrinogen. One part tissue factor, 250 mmol/l CaCl(2), generating about 1 IU/ml thrombin within 1 min (37 degrees C). After 0-30 min 2.5 mol/l arginine (pH 8.6) Generated thrombin was detected by addition of CHG-Ala-Arg-pNA and measurement of triangle upA/t. The EXCA is dependent on factors 10% of the factor VII norm in the sample achieves 70 80% of the thrombin generation norm. The EXCA is not dependent on factors VIII, IX, XI and XII. Even in antithrombin III-deficient plasma, a phase of thrombin inhibition appears after the thrombin peak. Supplemented purified fibrinogen resulted in decreased thrombin generation in the important. Fibrinogen seems to act as antithrombin I; thrombin might be entrapped in the nascent fibrin. The EXCA is suitable to diagnose the level of extrinsic factors in patient plasma. PMID- 17287626 TI - Hyperhomocysteinemia and the compound heterozygous state for methylene tetrahydrofolate reductase are independent risk factors for deep vein thrombosis among South Indians. AB - To investigate the role of methylene tetrahydrofolate reductase (MTHFR) (677 C- >T and 1298 A-->C), factor V (1691 G-->A), factor II (20210 G-->A) genetic polymorphisms and hyperhomocysteinemia in the aetiology of deep vein thrombosis (DVT) in 163 cases and 163 controls. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping, reverse-phase high performance liquid chromatography for plasma homocysteine, and Student's t-test and Fisher exact tests were used for statistical analysis. Elevated mean plasma homocysteine levels were observed in DVT cases irrespective of gender differences. Homocysteine elevation above the 95th percentile of the control group associated with 9.4-fold and 7.6-fold increased risk for DVT in men and women, respectively. Genotyping showed the MTHFR 677CT/1298AC genotype (i.e. compound heterozygosity) is associated with 3.5-fold risk for thrombosis. The factor V Leiden mutation frequency was higher in DVT cases, but not statistically significant; however, genetic predisposition to this mutation was associated with early age of DVT onset. Factor II mutation was absent in cases and controls. Co segregation of two or more risk factors was associated with 11.7-fold increased risk for thrombosis. This study projects that hyperhomocysteinemia and compound heterozygous state for MTHFR are independent risk factors for DVT among South Indians. PMID- 17287627 TI - A functional clotting assay to monitor the hirudin dosage. AB - Hirudin, a direct thrombin inhibitor, has potential advantages over indirect thrombin inhibitors and is increasingly used in clinical settings. There are, however, large variations in individual responses to this drug and no recognized clinical laboratory tests used to monitor its anticoagulant effects. We evaluated the use of the thromboelastograph, a common clinical coagulation instrument, to monitor the effects of hirudin in vitro. We developed a novel, whole blood clotting assay that utilizes the tissue factor stimulating properties of mercuric ion to measure the anticoagulant potential of therapeutic doses of hirudin. At doses equivalent to those found in the therapeutic range, the thromboelastograph was capable of showing significant changes when compared with control and different concentrations of hirudin (P < 0.05). A linear relationship was observed between increasing concentrations of recombinant hirudin and clotting times. In conclusion, the use of this test system warrants further investigation for monitoring hirudin. PMID- 17287628 TI - Increased factor VIII coagulant activity levels in male carriers of the factor V R2 polymorphism. AB - A common factor V gene haplotype, the FVR2 haplotype (FVHR2), has been associated with a reduced cofactor activity in activated protein C-mediated activated factor VIII inactivation. Our aim was to investigate the role of FVHR2 as a possible determinant of factor VIII levels in a population study. A total of 516 individuals (401 men, 115 women; mean age 58.4 +/- 10.8 years) were enrolled within the frame of a regional cardiovascular survey, characterized for factor VIII coagulant activity (FVIII:c) and factor V coagulant activity (FV:c) levels, and genotyped for factor V polymorphisms. In men without signs of overt inflammation, FVHR2 carriers had higher levels of FVIII:c than noncarriers (154 IU/dl, 95% confidence interval = 143-166 versus 142 IU/dl, 95% confidence interval = 138-147; P = 0.045) and were more represented in individuals with high (> or = 150 IU/dl) FVIII:c levels (21.2 versus 10.8%; odds ratio = 2.27, 95% confidence interval = 1.17-4.39 after adjustment for age, blood group and high sensitivity C-reactive protein levels). In conclusion, this clinical report suggests the common FVHR2 as a possible independent determinant of FVIII:c levels. The report concomitantly addresses the relationship between factor V and factor VIII levels and supports the hypothesis of a mild prothrombotic role of FVHR2 by means of increased factor VIII levels. PMID- 17287629 TI - Efficacy of elastic compression stockings used early or after resolution of the edema on recanalization after deep venous thrombosis: the COM.PRE Trial. AB - Elastic compression stockings are useful for preventing post-thrombotic syndrome after deep venous thrombosis (DVT). Less is known about their effects on thrombus recanalization and the optimal timing for starting compression. This study investigated whether compression applied early was more effective than when started 2 weeks after DVT. Seventy-three patients with DVT were randomly assigned to elastic compression hosiery starting either immediately after diagnosis or 2 weeks later. After 14 and 90 days the residual thrombus was measured by compression ultrasonography, and venous patency and any pathological reflux were recorded. There were significantly more recanalized venous segments in the group treated with early compression. Recanalization of popliteal DVT veins, expressed as the reduction of vein diameter, was also better in the early compression group than controls (day 14, 6.5 +/- 3 versus 5 +/- 2 mm, P = 0.035; day 90, 3.7 +/- 3 versus 2.1 +/- 1.7 mm; P = 0.014). On day 14 the mean score for popliteal patency was significantly better for the early compression patients (1.0 +/- 0.6 versus 1.5 +/- 0.5, P = 0.0015). In conclusion, elastic compression applied immediately at diagnosis of DVT was safe and effective on the surrogate end-points investigated in this study. Longer follow-up in larger series is needed to verify the patterns of recurrence of DVT and post-thrombotic syndrome. PMID- 17287630 TI - Age estimates of ancestral mutations causing factor VII deficiency and Dubin Johnson syndrome in Iranian and Moroccan Jews are consistent with ancient Jewish migrations. AB - Factor VII (FVII) deficiency and Dubin-Johnson syndrome (DJS) are rare autosomal recessive disorders caused by mutations in F7 and MRP2 genes, respectively. Both disorders are relatively frequent among Iranian and Moroccan Jews. FVII deficiency in both populations is caused by a founder A244V mutation in the F7 gene and DJS is caused by two founder mutations, I1173F and R1150H in the MRP2 gene that are specific for Iranian and Moroccan Jewish patients, respectively. We estimated the age of FVII A244V and MRP2 I1173F by analysis of microsatellite markers flanking F7 and MRP2 genes, respectively, in 13 Iranian Jewish homozygotes for the I1173F mutation and 21 Iranian and Moroccan Jewish homozygotes for the A244V mutation. Dating of the mutations was estimated by the DMLE+2.0 program employing observed linkage disequilibria of multiple genetic markers. The estimated age of the I1173F mutation was approximately 1500 years, and the age of the A244V mutation was approximately 2600 years. These estimates suggest that I1173F causing DJS in Iranian Jews occurred after the separation of Iranian Jews from Moroccan Jews 2000-2600 years ago, while A244V causing FVII deficiency in Iranian and Moroccan Jews occurred prior to the divergence of these two populations. PMID- 17287631 TI - Thrombelastographic method to quantify the contribution of factor XIII to coagulation kinetics. AB - Factor XIII (FXIII) plays a critical role in clot strength, and FXIII deficiency or excess is associated with hemorrhage or thrombosis, respectively. Our goal was to design a thrombelastography-based method to characterize the effects of FXIII on plasma clot strength. Normal human plasma was exposed to 0 or 200 mug/ml anti FXIII antibodies for 20 min prior to celite activation and calcium addition. Other plasma had addition of fibrinogen (625 mg/dl)/FXIII (2 U/ml) or 30% dilution with hydroxyethyl starch before exposure to 0 or 200 mug/ml anti-FXIII antibodies. Thromboelastography was performed and data were collected until stable clot strength was observed. The exposure of normal plasma to anti-FXIII antibodies resulted in a significant (P < 0.05) decrease in clot strength (63%) compared with plasma without antibodies. Further samples exposed to anti-FXIII antibodies had clot strength no different from FXIII-deficient plasma. The FXIII mediated clot strength varied between 44 and 50% in hypercoagulable and hypocoagulable plasma, respectively. In conclusion, the present investigation successfully demonstrated a novel method to detect the impact of FXIII activity in plasma samples. Further actuarial investigation will be required to determine the utility of this approach in the diagnosis and treatment of patients with either acquired FXIII deficiency or excess and concordant coagulopathy. PMID- 17287632 TI - A new nitrate derivative of piperazine: its influence on platelet activity. AB - Nitric oxide (NO) is a potent vasodilator and inhibitor of platelet activation. Its donors, organic nitrates, are still a main group of drugs administered in ischaemic heart disease. The aim of this study was to investigate the effect of a new NO-donor analogue, 1-(3-piperidinepropionyl)-4-(2-nitrooxy-3 piperidinepropyl) piperazine trihydrochloride (NO-P), on platelet activity. Its influence on the main mechanisms of human platelet activation (adhesion, shape change, secretion and aggregation) was evaluated with the use of a pharmacological model produced on the basis of known platelet activation measuring methods and our computer program. Our experiments revealed that the new NO derivative of piperazine favourably influences platelet activity, and decreases adhesion (spontaneous and induced by ADP) and aggregation. NO-P shows the same direction of action as nitroglycerin (used as a model compound), and is even stronger in the case of ADP-induced and collagen-induced aggregation. These findings broaden the possibility of using NO-P in cardiovascular diseases. Furthermore, our computer program, used to evaluate kinetic parameters of platelet aggregation, shape change, and the adhesion measuring method, provides a simple and accessible experimental model. This model can be useful in in-vitro screening studies, estimating the influence of new compounds (potential drugs) on platelet activity. PMID- 17287633 TI - Lipopolysaccharide down-regulates the thrombomodulin expression of peripheral blood monocytes: effect of serum on thrombomodulin expression in the THP-1 monocytic cell line. AB - Thrombomodulin has a central role in the regulation of coagulation through its abilities to promote generation of the potent anticoagulant activated protein C. Because little is known about monocyte thrombomodulin expression and its regulatory mechanism by lipopolysaccharide, we investigated the effect of lipopolysaccharide on monocyte's thrombomodulin expression. Lipopolysaccharide reduced the surface thrombomodulin expression of human peripheral blood monocytes in a dose-dependent and time-dependent manner, regardless of the addition of serum. The surface thrombomodulin activity was comparably decreased in monocytes incubated with lipopolysaccharide. Blocking nuclear factor-kappaB by MG132 or aurine tricarboxylic acid effectively inhibited the lipopolysaccharide-induced surface thrombomodulin down-regulation of monocytes. Lipopolysaccharide inactivation by polymyxin B in the supernatants from the lipopolysaccharide stimulated cultures still reduced the surface thrombomodulin expression of monocytes, suggesting a role for soluble mediators in the down-regulation of thrombomodulin. The lipopolysaccharide-induced thrombomodulin surface expression and the mRNA levels of the monocytic leukemic cell line (THP-1) were decreased in serum-depleted culture, while they were increased in medium containing 10% serum. We conclude that lipopolysaccharide down-regulates the thrombomodulin expression of monocytes and that nuclear factor-kappaB is a critical mediator of the repression of thrombomodulin by lipopolysaccharide. Regulation of the THP-1 thrombomodulin expression by lipopolysaccharide depends on the presence of serum. PMID- 17287634 TI - Premature compared with late onset of coronary artery disease: young patients show a severe defect in fibrinolytic response to venous occlusion. AB - Inflammatory processes play a role in the onset of acute cardiovascular events associated with activation of the coagulation system whereas the fibrinolytic system may prevent local thrombus formation. We compared 25 patients with premature coronary artery disease (CAD) (first ST-elevation myocardial infarction, < 55 years old) with 25 sex-matched patients older than 55 years at their first myocardial infarction. Six months after the acute event, patients with late onset of CAD showed a significantly higher increase of tissue-type plasminogen activator activity during venous occlusion compared with patients with premature CAD (P < 0.005). Prothrombin fragment 1+2 was higher in patients with late-onset CAD (P < 0.05), whereas the inflammatory markers C-reactive protein and soluble intercellular cell adhesion molecule-1 were not different in both groups. A multivariate analysis including cardiovascular risk factors showed that the tissue-type plasminogen activator response to venous occlusion was independently associated with patient age at onset of first ST-elevation myocardial infarction. Although in our series high age was associated with a prothrombotic state, a high fibrinolytic capacity might have some beneficial effect and contribute to a delayed onset of adverse cardiovascular events in these patients. PMID- 17287635 TI - Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism. AB - This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38 4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization. PMID- 17287636 TI - Analysis of hemostasis alterations in sepsis. AB - This laboratory study tested new methods to analyze hemostasis alterations in septic patients. Samples of ethylenediamine tetraacetic acid (EDTA) plasma and citrated plasma were collected from 62 patients with clinical diagnosis of sepsis. Additionally, a subset of EDTA-plasma samples from each patient was stabilized 1 + 1 with 2.5 mol/l arginine, pH 8.6, to conserve the real hemostasis activation state. EDTA-arginine plasma, EDTA plasma and citrated plasma samples were tested in duplicate. The patients at admission to the intensive care unit had 36 +/- 26 (normal, 0.8 +/- 0.2) ng/ml global endotoxin reactivity, 188 +/- 66% (normal, 100 +/- 20%) fibrinogen function, 179 +/- 66% (normal, 100 +/- 20%) fibrinogen antigen, 4.0 +/- 3.6 (normal, 0.049 +/- 0.025) microg/ml D-dimer, 313 +/- 307% (normal, 100 +/- 30%) plasmin-antiplasmin complex, 8.7 +/- 11.4 (normal, 1.1 +/- 0.7) U/ml plasminogen activator inhibitor-1, 12.1 +/- 10.5 (normal, 1.3 +/- 0.4) ng/ml thrombin-antithrombin III complex, 173 +/- 62% (normal, 100 +/- 20%) thrombin, 568 +/- 225 (normal, 140 +/- 42) pg/ml tissue factor, and 2.56 +/- 2.48 (normal, 0.19 +/- 0.04) microg/ml soluble intercellular adhesion molecule-1. Endotoxin (lipopolysaccharide and/or beta-glucan) reactivity (EDTA plasma), fibrinogen function + antigen + ratio and plasminogen activator inhibitor-1 (citrated plasma), and D-dimer, soluble intercellular adhesion molecule-1, thrombin activity (EDTA-arginine-stabilized plasma) presented large aberrations in septic patients when compared with normal values and may therefore be particularly interesting as markers of hemostasis alteration. Whether the observed alterations are of clinical significance has to be determined in well defined patient groups. PMID- 17287637 TI - Clinical relevance of aspirin resistance in patients with stable coronary artery disease: a prospective follow-up study (PROSPECTAR). AB - Aspirin resistance may increase the risk of major adverse cardiac events (MACE) more than threefold in patients with stable coronary artery disease (CAD). This study aimed to determine the prevalence of aspirin resistance in patients with stable CAD, the role of aspirin resistance on outcome in the follow-up, and the effect of clopidogrel therapy in MACE prevention in aspirin-resistant individuals. We detected the prevalence of aspirin resistance in 234 patients with stable CAD. Platelet function was determined by PFA-100 with collagen and/or epinephrine and collagen and/or ADP cartridges. The mean follow-up time was 20.6 +/- 6.9 months. The primary endpoints of the study were occurrence of myocardial infarction, unstable angina, stroke and cardiac death. Of patients, 22.2% (n = 52) were aspirin resistant by PFA-100. During follow-up, MACE occurred in eight patients (15.4%) with aspirin resistance and in 20 patients (11.0%) with aspirin sensitive platelet aggregation (P = 0.269). MACE increased in aspirin-resistant patients after termination of clopidogrel therapy. Eleven patients experienced MACE after cessation of clopidogrel therapy (P < 0.001). The MACE risk in patients with stable CAD having detected aspirin resistance was similar compared with patients having aspirin-sensitive platelet aggregation by PFA-100. The MACE prevalence increased during follow-up, however, just after cessation of clopidogrel therapy. PMID- 17287638 TI - Feasibility of treating hyperfibrinogenemia with intermittently administered batroxobin in patients with ischemic stroke/transient ischemic attack for secondary prevention. AB - This study evaluated the safety and efficacy of batroxobin in treating hyperfibrinogenemia for secondary stroke prevention. Patients with ischemic stroke or transient ischemic attack (TIA) were measured for plasma fibrinogen levels. Selected participants had concomitant hyperfibrinogenemia (plasma fibrinogen > or = 3.0 g/l). Patients enrolled between 1 July 2003 and 31 December 2004 were treated with batroxobin; patients enrolled between 1 January 2002 and 30 June 2003 were treated without batroxobin. Batroxobin was administered intermittently via intravenous injection at 3-monthly intervals. Patients in both groups were followed for 1 year. Any cerebrovascular events and suspected adverse events were recorded. In total, 112 ischemic stroke/TIA patients with concomitant hyperfibrinogenemia were enrolled, 52 being treated with batroxobin and 60 without batroxobin. Six patients (11.5%) with batroxobin and 16 patients (26.7%) without batroxobin had recurrent cerebral ischemic events during follow-up. Stroke/TIA recurrence in patients without batroxobin was higher than that in patients with batroxobin (P < 0.05). Two patients with batroxobin and two patients without batroxobin developed hemorrhagic stroke during follow-up. There were five deaths (9.6%) in the batroxobin group, and seven deaths (11.7%) in the nonbatroxobin group during follow-up (P > 0.05). Intermittent intravenous injection of batroxobin can efficiently reduce the risk for stroke/TIA recurrence in patients with concomitant hyperfibrinogenemia. PMID- 17287639 TI - Recombinant activated factor VII for hemostatic cover of orthopedic interventions in a girl with thrombocytopenia with absent radii syndrome. AB - Over the past 10 years recombinant activated factor VIIa (rFVIIa) has been successfully used for treatment and prophylaxis of bleeding in patients with platelet defects, including thrombocytopenia and congenital and acquired platelet function abnormalities. Most reported data concern patients with Glanzmann's thrombasthenia and the information available is still limited, especially for surgery. We report on a 15-year-old girl with thrombocytopenia ( approximately 60,000/microl) and platelet dysfunction (bleeding time 30 min, absent platelet aggregation and ATP secretion in response to collagen), related to thrombocytopenia with absent radii syndrome, undergoing two surgical interventions on the upper limbs due to forearm deformities, with prolonged postoperative revisions. In both surgeries rFVIIa was successfully employed as a bolus administration (80 microg/kg every 4 h during the first day, then every 6 h over the following 5 and 3 days, respectively; tranexamic acid was associated from the second day, administered for 2 weeks), avoiding the need for blood products. This report highlights rFVIIa as an attractive, alternative approach to secure hemostasis in patients with platelet defects; on the other hand, the heterogeneity of reported rFVIIa treatment regimens and, in particular, the lack of definite and easily available parameters (or assays) for monitoring rFVIIa efficacy and safety are the main open issues in this setting. PMID- 17287640 TI - A new case of combined factor V and factor VIII deficiency further suggests that the LMAN1 M1T mutation is a frequent cause in Italian patients. AB - Combined factor V and factor VIII deficiency (F5F8D) is an extremely rare worldwide congenital hemorrhagic disorder that is more prevalent in the Mediterranean area. We report the clinical presentations and the identification of a LMAN1 mutation in a 3-year-old Italian boy who was diagnosed with F5F8D. The mutation identified (M1T) has already been found in several Italian patients. Since the LMAN1 M1T mutation has been identified in most patients with F5F8D, we suggest that the search for this mutation should be the first step in the molecular characterization of patients from an Italian ethnic background. PMID- 17287641 TI - Successful management of intra-abdominal hemorrhage in the presence of severe alcoholic liver disease with activated recombinant factor VII (rFVIIa; NovoSeven): a case report and review of the literature on approved and off-label use of rFVIIa. AB - A 37-year-old male with history of alcohol abuse presented to us with nausea, vomiting, and abdominal pain with ascites. He was diagnosed with alcoholic liver disease with coagulopathy and pancreatitis. During hospitalization, the patient developed intra-abdominal hemorrhage. He was treated with platelets, packed red blood cells and fresh frozen plasma without any improvement. Following this he was treated with activated recombinant factor VII (90 microg/kg), which resulted in normalization of the prothrombin time and the activated partial thromboplastin time and stabilization of hematocrit within a few hours. We review the current literature on the approved and off-label use of activated recombinant factor VII. PMID- 17287642 TI - The anticoagulant capacity of plasmatic unfractionated heparin decreases at 23 degrees C. AB - Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are important clinical anticoagulants. As polynegative molecules they are potential triggers of the contact phase of coagulation. An incubation temperature lower than the physiological 37 degrees C favours intrinsic haemostasis activation by the polynegative molecule SiO2. The efficiency of UFH and LMWH after a plasmatic preincubation at 37 or at 23 degrees C is therefore studied. Samples (150 mul) of unfrozen pooled normal plasma supplemented with 0, 0.01, 0.1, or 1 IU/ml heparin or dalteparin in 5-ml polystyrole tubes were incubated for 10-70 min at 37 or at 23 degrees C. The extrinsic coagulation activity assay (EXCA) was then performed. Preincubation at 37 degrees C of 0.1 IU/ml plasmatic UFH does not result in any thrombin generation in EXCA-1, whereas preincubation at 23 degrees C results in a thrombin generation of about 0.1 IU/ml thrombin. Plasmatic UFH (0.01 IU/ml) at 23 degrees C acts nearly half as efficiently as 0.01 IU/ml plasmatic LMWH. Polynegatively charged niches particularly in the larger UFH molecule might trigger the contact system of haemostasis, especially at 23 degrees C. In contrast, the anticoagulant capacity of LMWH does not change significantly with temperature. PMID- 17287643 TI - Specific determination of plasmatic plasmin activity. PMID- 17287644 TI - Effect of the arterial input function on the measured perfusion values and infarct volumetric in acute cerebral ischemia evaluated by perfusion computed tomography. AB - OBJECTIVES: We sought to evaluate the accuracy of the perfusion computed tomography (PCT) deconvolution-based brain perfusion measurements and the lesions' (infarct and penumbra) volumetric with regard to arterial input function (AIF) selection in patients with acute stroke. MATERIALS AND METHODS: Eighteen consecutive patients with symptoms of acute stroke underwent PCT at admission. Follow-up magnetic resonance imaging was obtained in all patients after 3.6 +/- 1.7 days (range, 1.5-6 days). PCT maps were generated focusing on the anterior cerebral artery (ACA) and branches of the middle cerebral artery (MCA) ipsilateral and contralateral to the ischemic lesion as AIFs. Infarct, penumbra, and total ischemic lesion were delineated on cerebral blood flow (CBF) maps. CBF, cerebral blood volume (CBV), and mean transit time (MTT) were calculated in the ischemic regions as provided by the 3 different AIFs, the normality test was applied for the obtained parameters, and the values were correlated (Pearson's correlation coefficient). Volumes of the ischemic regions (as obtained by the different AIFs) also were correlated and compared (paired t test) to the follow up infarct volume. RESULTS: The CBF and CBV values obtained by the different AIFs in the infarct, penumbra, and total ischemic lesion were significantly correlated (r=0.94-0.96, P0.05). In the preliminary in vivo experiments, RFA created spherical coagulations at interprobe distances of 2 cm and 3 cm but at larger distances than 3 cm, RFA created partially confluent coagulation zones. In our principal experiments, switching RFA created areas of well-defined coagulation, ie, at a 2-cm interprobe distance, the volume and short axis coagulation diameter were 35.5+/- 5.7(3) cm and 4.6 +/- 0.5 cm, respectively, whereas at 3 cm, they were 40.7 +/- 12.8(3) cm and 4.8 +/- 0.8 cm, respectively. The mean values of the circularity (isometric ratio) of the coagulation at the 2- and 3-cm interprobe distances were 0.95 +/- 0.02, and 0.85+/- 0.06, respectively. CONCLUSIONS: Our study demonstrated that switching monopolar RFA using the multichannel RF system at a 2- or 3-cm interprobe distance and at a 30-second switching time can create a large, confluent coagulation zone in the liver within a clinically acceptable time frame. We believe that this technology will provide a useful tool for the treatment of large liver tumors. PMID- 17287647 TI - Quantitative measurements of perfusion and permeability of oropharyngeal and oral cavity cancer, recurrent disease, and associated lymph nodes using first-pass contrast-enhanced computed tomography studies. AB - OBJECTIVES: We sought to evaluate the routine clinical use of perfusion computed tomography in the detection and differentiation of primary and recurrent oropharynx and oral cavity tumors as well as of nodal disease. MATERIALS AND METHODS: A total of 77 patients with primary cancer as well as suspected recurrent disease and lymph nodes were evaluated. A dynamic acquisition (4 x 6-mm slices) of the largest axial tumor surface was performed and the tumor blood flow (BF), blood volume (BV), and mean transit time (MTT) were calculated by using a modified deconvolution-based analysis taking into account the extravasation of the contrast agent for permeability surface area product imaging (PS). Tumor volume was calculated and region of interest analysis was performed on the pathologic and normal tissue. RESULTS: The mean BF, BV, and PS values in the primary tumors (77.48 mL/min/100 g tissue; 5.29 mL/min; 13.33 mL/min/100 g tissue, respectively) were highly significantly different (P < 0.01) than those obtained in the normal structures. Mean MTT values (9.01 seconds) also were significantly lowered in the tumors compared with normal tissue (P < 0.05). There was no statistical difference in the perfusion values between the primary and the recurrent tumors. Recurrent disease could be differentiated on the basis of BF (P < 0.05) from tissue changes after chemo-radiation-treatment (mean BF: 69.71 versus 45.31 mL/min/100 g tissue, respectively). Differentiation of the lymph nodes was not possible by means of perfusion values. Tumor volume did not significantly correlate with any perfusion parameter. CONCLUSIONS: Perfusion CT of oropharyngeal and oral cavity cancer in clinical routine is feasible and helps outlining the malignant tissue as well as differentiating recurrent disease from nonspecific post-therapeutic changes. PMID- 17287648 TI - Cardiac phase-resolved blood oxygen-sensitive steady-state free precession MRI for evaluating the functional significance of coronary artery stenosis. AB - OBJECTIVE: This study investigates whether cardiac phase-resolved steady-state free precession (SSFP) magnetic resonance imaging can be used to detect regional myocardial oxygen deficits (MODs) and other functional changes (wall motion and ejection fraction) caused by coronary artery stenosis in a canine model. MATERIALS AND METHODS: Subsequent to changing the degree of stenosis of the left circumflex arteries of 8 dogs, cardiac phase-resolved SSFP images were acquired at baseline, prestensois (with adenosine), and at different stenosis levels and were correlated against true flow changes. Wall motion and ejection fraction changes also were assessed under the different stenosis levels. RESULTS: MODs caused by coronary stenosis were observed with the SSFP-based technique and were strongly correlated with microsphere-based regional flow measurements (r=0.80, P<0.01). From the phase-resolved SSFP images, statistically significant (P < 0.01) changes in wall motion and ejection fraction were also observed at severe stenosis. CONCLUSION: The SSFP method can simultaneously detect MODs, wall motion changes, and left ventricular dysfunction caused by coronary artery stenosis within a single scan in a controlled canine model. PMID- 17287649 TI - Influence of a lipid-lowering therapy on calcified and noncalcified coronary plaques monitored by multislice detector computed tomography: results of the New Age II Pilot Study. AB - PURPOSE: Multislice detector computed tomography (MSCT) is an accurate noninvasive modality to detect and classify different stages of atherosclerosis. The aim of the New Age II Study was to detect coronary lesions in men without established coronary artery disease (CAD) but with a distinct cardiovascular risk profile. We also sought to assess the effect after 1 year of a lipid-lowering therapy (LLT) using 20 mg of atorvastatin. METHODS: Forty-sixe male patients (mean, 61 +/- 10 years) with an elevated risk for CAD (PROCAM score >3 quintile) without LLT were included. Native and contrast-enhanced scans were performed in all patients. A total of 27 of 46 patients received a follow-up scan (after 488 +/- 138 days). Coronary plaque burden (CPB) was assessed volumetrically. RESULTS: The prevalence of CAD was 83% (38/46 patients), and 11% (5/46) without coronary calcifications still had noncalcified plaques. Total cholesterol and low-density lipoprotein cholesterol levels decreased significantly under LLT (225 +/- 41 mg/dL vs. 162 +/- 37 mg/dL, P < 0.0001 and 148 +/- 7 mg/dL vs. 88 +/- 5 mg/dL, P < 0.001, respectively). On follow-up, calcium score and CPB remained unchanged (Agatston score: 261 +/- 301 vs. 282 +/- 360; CPB: 0.149 +/- 0.108 vs. 0.128 +/- 0.075 mL, P > 0.05), whereas mean plaque volume of noncalcified plaques decreased significantly from 0.042 +/- 0.029 mL versus 0.030 +/- 0.014 mL (P < 0.05, mean reduction 0.012 +/- 0.017 mL or 24 +/- 13%). CONCLUSIONS: Statin therapy led to a significant reduction of noncalcified plaque burden that was not reflected in calcium scoring or total plaque burden. This finding might explain the risk reduction after the initiation of statin therapy. Using multislice detector computed tomography, physicians have the potential to monitor medical treatment in patients with coronary atherosclerosis. PMID- 17287650 TI - Dual-source computed tomography: advances of improved temporal resolution in coronary plaque imaging. AB - OBJECTIVES: The aim of this study was to quantify image quality gains of a moving coronary plaque phantom using dual-source computed tomography (DSCT) providing 83 milliseconds temporal resolution in direct comparison to 64 slice single-source multidetector CT (MDCT) with a temporal resolution of 165 milliseconds. MATERIALS AND METHODS: Three cardiac vessel phantoms with fixed 50% stenosis and changing plaque configurations were mounted on a moving device simulating cardiac motion. Scans were performed at a simulated heart frequency of 60 to 120 bpm. Image quality assessment was performed in different anatomic orientations inside a thoracic phantom. RESULTS: A significant improvement of image quality using the DSCT could be found (P=0.0002). Relevant factors influencing image quality aside from frequency (P=0.0002) are plaque composition (P<0.0001), as well as orientation (P<0.0001). CONCLUSION: Scanning with 83 milliseconds temporal resolution improved image quality of coronary plaque at higher heart frequencies. PMID- 17287651 TI - High-resolution complementary spatial modulation of magnetization (CSPAMM) rat heart tagging on a 1.5 Tesla Clinical Magnetic Resonance System: a preliminary feasibility study. AB - The purpose of this study was to assess the feasibility of cardiac magnetic resonance (MR) tagging in rats on a standard clinical 1.5T MR system. Small animal models have been largely used as an experimental model in cardiovascular disease studies but mainly on high field systems (>4T) dedicated to research. Given the larger availability of routine clinical MR systems in centers with active cardiac research programs, it is of great interest to perform small animal imaging on whole-body MR systems of moderate field strength. The feasibility study was performed on 7 rats within 6 to 8 hours after myocardial infarction and 3 normal control rats. Myocardial strain was measured successfully in normal rats using the harmonic phase (ie, HARP) method, and a transmural gradient was demonstrated. In a rat model of acute occlusion/reperfusion, the myocardial circumferential strains were decreased, but the transmural strain gradient was preserved. This study demonstrated the feasibility of cardiac MR tagging in rats with a subendocardial resolution using a clinical 1.5T system. PMID- 17287652 TI - Secondary intracanalicular extension of a primary intracochlear schwannoma. PMID- 17287654 TI - Long-lasting deviation of the subjective visual horizontal after complete unilateral vestibular deafferentation by subtotal resection of the temporal bone. AB - OBJECTIVE: This study examined whether subjective visual horizontal (SVH) could be compensated in patients with complete loss of unilateral vestibular function. PATIENTS: Patients comprised two men and three women who underwent subtotal resection of the unilateral temporal bone due to squamous cell carcinoma of the middle or external ear. Mean patient age was 63.2 years (range, 59-69 yr). INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Patients were tested postoperatively (mean, 4 yr 5 mo after the surgery; range, 2 yr 9 mo to 8 yr 6 mo). The task for patients involved adjusting a laser projection bar four times to SVH in darkness. RESULTS: All patients displayed marked deviation of SVH toward the operated side-down. Mean deviation from four trials for each subject was 4.5, 2.9, 3.7, 3.0, and 3.4 degrees. CONCLUSION: Deviation of SVH in patients with definite unilateral vestibular deafferentation can be long term, lasting more than 2 years at least. PMID- 17287657 TI - Delayed facial palsy in a patient with a bifid facial nerve lending support for viral theory of facial palsy. AB - OBJECTIVE: To describe the level of neurologic impairment in a case of delayed facial palsy occurring after cochlear implantation surgery. PATIENT: A 58-year old man undergoing cochlear implantation who was found intraoperatively to have congenital bifurcation of the facial nerve just distal to the second genu. INTERVENTION: Cochlear implantation was performed through a facial recess approach. RESULTS: The lateral branch of the nerve impinged on the posterior tympanotomy slot and was uncovered during the procedure, rendering it vulnerable to direct thermal or mechanical injury or to the effects of local tissue injury products. The patient developed facial palsy 9 days later, affecting all facial muscle groups equally. CONCLUSION: Theories regarding the cause of delayed facial palsy after cochlear implantation include direct thermal or mechanical injury to the nerve, local effects of blood breakdown products or other mediators causing vasospasm, and reactivation of latent herpes virus, leading to neural inflammation and neuropathy of the geniculate and labyrinthine segments of the nerve. The fact that the patient developed weakness that affected all facial muscle groups equally suggests that the level of neurologic impairment was proximal to the nerve bifurcation, so distant to the actual site of surgery. This finding lends support for the viral hypothesis of delayed nerve palsy. PMID- 17287658 TI - Intracanalicular meningioma: clinical features, radiologic findings, and surgical management. AB - OBJECTIVE: Intracanalicular meningiomas are extremely rare, and only 36 cases have been reported to date. The aim of this study is to describe the clinical, radiologic, and histopathologic features of 13 intracanalicular meningiomas highlighting important aspects of tumor diagnosis and treatment. STUDY DESIGN: Retrospective study. SETTING: Quaternary referral otology and cranial base private center. PATIENTS: Thirteen consecutive patients with pathologically confirmed intracanalicular meningioma surgically treated between December 1988 and July 2006. The follow-up of the series ranged from 13 to 60 months. INTERVENTIONS: Nine patients with unserviceable hearing were operated on through the translabyrinthine approach. Four patients underwent enlarged middle cranial fossa approach with the intention of preserving their hearing. RESULTS: Total tumor removal was achieved in all cases. The postoperative facial nerve function was either excellent or good (House-Brackmann Grade I or II) in 10 cases (77%) and acceptable (Grade III) in one case. Two patients with preoperative facial paresis showed no improvement in their facial nerve function. In patients who underwent surgery via the enlarged middle cranial fossa, hearing was preserved at the preoperative level in two cases, but serviceable hearing was lost in the remaining two. CONCLUSION: Primary meningiomas of the internal auditory canal are extremely rare. On account of a lack of specific symptoms and the limited diagnostic findings, preoperative diagnosis of intracanalicular meningioma still represents a diagnostic challenge. Intraoperative findings may help in differentiating meningiomas from other intracanalicular lesions. PMID- 17287659 TI - Bony sheathed chorda tympani: a unique case of incudomalleolar fixation. AB - OBJECTIVE: To describe a unilateral conductive hearing loss caused by restriction of the movements of malleus and incus due to chorda tympani in a bony sheath. PATIENT: A 23-year-old man with a stable mild conductive hearing loss in the left ear and mild sensorineural hearing loss in the right ear. INTERVENTION: An exploratory tympanotomy was performed. MAIN OUTCOME MEASURE: Immobility of the ossicles due to a bony structure, which was found to be chorda tympani encircled in a bony sheath. Ossicular system regained its mobility with the severance of the chorda tympani. RESULTS: Hearing was improved both subjectively and audiographically. CONCLUSION: This is the second case of chorda tympani with a bony sheath and the first case of this pathologic finding affecting both malleus and incus. Bony sheathed chorda tympani is considered to be a congenital anomaly of the chorda tympani that causes incudomalleolar fixation and behaves as posterior bony bars. PMID- 17287660 TI - Ear canal keratinocyte culture: clinical perspective. AB - HYPOTHESIS: Autologous epidermal sheets obtained by cultivating keratinocytes of the external auditory meatus can be used to repair cutaneous defects of the ear canal. The Rheinwald and Green method has been used to know whether the produced epidermal layer preserves its specificities after the culture. BACKGROUND: Using a split-thickness skin graft during a functional ear atresia surgery does not allow for the restitution of external auditory canal self-cleaning. Some authors cultivated external auditory meatus keratinocytes and showed migration capacities of these colonies. METHODS: Samples of preauricular skin and of the bony part of the external auditory canal were harvested from 10 patients. Keratinocytes were extracted and cultured until an epidermal sheet was obtained. The output, the keratinocyte plating efficiency, and the production delay were measured during the culture. Culture product sections and biopsy sections were examined using optical microscopy after standard coloration and indirect immunohistochemistry. RESULTS: Nine epidermal layers from 10 biopsies were obtained in each group. A significant difference between external auditory meatus and preauricular keratinocyte plating efficiency was highlighted. The average production delay of 23 cm2 external auditory canal and preauricular epidermal layers was 21 days. There was no difference in the cytokeratine expression between external auditory canal and preauricular skin, nor between external auditory canal and preauricular culture products. All cultures expressed the cytokeratine 5 characteristic of stratifying epithelium. CONCLUSION: The Rheinwald and Green keratinocyte culture method allows the production of ear canal-stratified epidermal sheets, which can be used for external ear reconstruction. PMID- 17287662 TI - Three-dimensional morphology of the vestibular cleft and its potential application. AB - HYPOTHESIS: To delineate quantitatively the spatial relationships of the utricle, saccule, and stapedial footplate, to locate the hole on the footplate, and to analyze the insertion depth into the vestibule and the direction of the piston during stapedotomy. BACKGROUND: The quantitative three-dimensional (3D) configuration of the utricle, saccule, and stapedial footplate is undetermined, and the stapedotomy procedures should be improved. METHODS: Four temporal bones were extracted from the fresh cadavers and were undecalcified polymer-embedded. The specimens were sectioned into serial 50-mum-thickness slices. After image processing and 3D reconstruction, a cartesian coordinate system was established to display the spatial relationships of the utricle, saccule, and stapedial footplate in the 3D Studio Max scene. The configuration of the utricle, the saccule, and the "vestibular cleft" was delineated quantitatively with the contour map method. With this contour map, any distance between one point at the surface of the footplate and another point at the surface of the utricle or saccule and its orientation can be measured. RESULTS: There was a V-shaped cleft between the utricle and the saccule named vestibular cleft. The angle of the cleft was 50.30 degrees +/- 19.90 degrees . The apex of the cleft always directed anterosuperiorly, whereas beneath the posteroinferior part of the footplate was an open and deep "seabed." The vertical distances between points on the tympanic surface of the footplate and points on the surface of the utricle or saccule were measured. The vertical distance from the center point of footplate to the vestibular end organs was 2.20 +/- 0.548 mm, the maximum distance being 3.0 mm, whereas the minimum distance was 1.6 mm. CONCLUSION: The posteroinferior area near the central point of the footplate is the optimal position for the fenestra through which the piston can be inserted relatively safely into a depth of 0.8 to 1.0 mm in the vestibule. If the deep end of the piston is inclined inferiorly and posteriorly by 8 to 10 degrees, respectively, the piston will be farther from the vestibular end organs. These manipulations may enhance surgical safety and efficiency in stapedotomy. PMID- 17287663 TI - [Gillespie syndrome: an uncommon presentation of congenital aniridia]. AB - We report here the case of a patient suffering from Gillespie syndrome (GS) (partial aniridia, mental retardation, and cerebellar ataxia). The typical presentation is based on fixed dilated pupils in a hypotonic child. Iris abnormalities distinguish GS from other forms of aniridia. At the time of initial presentation, neurological involvement and radiologic abnormalities could be absent or delayed. Genetic determinism is still unknown. The pattern of inheritance seems to be heterogeneous, according to the autosomal recessive and autosomal dominant forms previously described. PMID- 17287664 TI - [Oguchi disease or stationary congenital night blindness: a case report]. AB - INTRODUCTION: Oguchi disease, originally described in Japanese people, is a rare form of stationary night blindness in patients with normal acuity. OBSERVATION: We report the case of an 8-year-old girl who presented with an abnormal terrified behavior in the dark. Thorough questioning revealed hemeralopia. Her clinical examination (visual acuity, Goldmann visual field, and color vision) were normal. The fundus examination showed golden-brown color, grayish, almost greenish yellow discoloration in the peripheral area with no osteoclast. This abnormality disappeared after prolonged dark adaptation. The electroretinogram showed a reduced b wave amplitude under scotopic conditions. Her parents were cousins. CONCLUSION: This diagnosis should be suggested when hemeralopia is associated with typical fundus aspect resolving after dark adaptation (so called Mizuo Nakamura phenomenon). The long-term prognosis in these patients is good in the absence of clinical progression. This is a genetic autosomal recessive disease caused by mutations in the gene coding for arrestin located in 2q37.1. PMID- 17287666 TI - [Long-term changes in pupil size after implantation of an Artisan phakic intraocular lens for correction of high myopia]. AB - PURPOSE: To evaluate the long-term changes in pupil size after implantation of an Artisan phakic intraocular lens for correction of high myopia. PATIENTS AND METHODS: Fourteen myopic eyes of seven patients were included in the study. Pupil size was measured under photopic conditions, under scotopic conditions after 10 min of dark adaptation, and after topical medical mydriasis. The pupil size was measured using the eye image of the OPD scan (Nidek). RESULTS: The mean follow-up was 46 months after surgery. The mean photopic pupil diameter was 2.94+/-0.33 mm (range, 2.54-3.6 mm). The diameter of the scotopic pupil remained less than 6.0 mm in all patients (4.68+/-0.59 mm, with maximal pupil diameter of 5.67 mm). The mean pupil diameter after pharmacological dilation was also reduced (5.39+/-1.08 mm; range, 4.19-7.59 mm), with pupil dilation more than 7 mm in only one patient. CONCLUSION: The iris-fixated intraocular lens mechanically limited pupil dilation in our patients. The long-term reduction in pupil size after Artisan phakic intraocular lens implantation may contribute to the maintenance of the quality of vision in scotopic conditions. PMID- 17287665 TI - [Eyelid chondroid syringoma: a case report]. AB - Chondroid syringoma is a rare benign skin tumor of the head and neck. Only 15 cases presenting on the eyelid have been described in the literature. An 84-year old patient presented with an 8-mm nodule on the right inferior eyelid that had grown over 5 years. The lesion was surgically removed, and the histopathological examination showed a chondroid syringoma. Knowledge of this disease is important because malignant transformations do occur. PMID- 17287667 TI - [Ex-PRESS miniature glaucoma implant inserted under a scleral flap in open-angle glaucoma surgery: a retrospective study]. AB - PURPOSE: (1) To present the Ex-PRESS device implanted under a scleral flap in open-angle glaucoma patients and to report its safety and efficacy; (2) to compare the results obtained without a scleral flap in a glaucoma group. PATIENTS AND METHODS: The case series studied included the eyes of Caucasian patients (82 patients, 99 eyes) with open-angle glaucoma, operated on between January 2003 and June 2004. The Ex-PRESS devices were inserted under the scleral flap in the anterior chamber; if necessary a combined surgery was performed (28 eyes). Each patient underwent ophthalmic examinations (IOP, visual field, gonioscopy, cup/disc ratio) before and after the operation. The surgical procedure lasted between 10 and 20 min with topical anesthesia. An antimetabolite was used under the scleral flap for all patients. The mean follow-up was 7.5+/-4.6 months; 40% had 12 months follow-up (40 eyes). RESULTS: The IOP decreased from 22.9+/-5.3 mmHg preoperatively to 14+/-2 mmHg at 6 months and 14.3+/-2.3 mmHg at 1 year. The success rate was 86.9% (IOP below 21 mmHg with or without drugs). Complete success was achieved in 62.6% (IOP below 21 mmHg without anti-glaucoma drops or medications). In 13 eyes, IOP was not controlled with eye drops, and nine eyes had to be reoperated. Six cases presented athalamia but recovered without surgical treatment. We did not observe any infection, corneal erosion, or Ex PRESS extrusion. There were no statistical differences between results obtained with and without scleral flap regarding IOP or early complications (athalamia). CONCLUSION: Both the safety and the efficacy of the device under a scleral flap were showed in glaucoma surgery in this retrospective study. Using the scleral flap reduces the risk of erosion but confirmation with a longer follow-up is needed. PMID- 17287668 TI - [Ultrasound biomicroscopy and physiopathology of congenital iris cysts]. AB - AIMS: Iris epithelial cysts, congenital or acquired, are rare tumors of the anterior chamber. The use of ultrasound biomicroscopy (UBM) and high-resolution echography (50 MHz) specified the diagnosis and confirmed the developmental hypothesis. METHODS: UBM examination with general anesthesia can provide very good vision of cysts and iris structure similar to histological examination. Successive slices are systematically produced. We report two cases: one in a 3 month-old boy with a pupillary type of pigment epithelial cyst and one in a 23 month-old boy with stromal iris cyst provides new information on iris cysts. RESULTS: UBM can clearly differentiate two types of cyst, with results similar to histological slice examination. UBM slices of iris edge cysts show small cellular parietal groups with stromal echogenicity, with no visible tissular continuity. The stromal cyst has no particularity and no echogenicity. DISCUSSION: The pupillary type of pigment epithelial cyst was generally recognized very early. The great majority of primary iris cysts, particularly those that arise from the iris pigment epithelial layers, are stable lesions that rarely progress or cause visual complications. Their slow progression could be explained by embryological history. Based on a comparison between the aspects of the two observations, the absence of enlargement of the cyst could be explained by the developmental mechanism. CONCLUSION: The advantage of the UBM in diagnosis is confirmed for very young patients, but also in developmental investigations. These case reports also corroborate the migration cellular theory during eye development to explain the appearance of the pupillary type of pigment epithelial cyst. PMID- 17287669 TI - [Treatment of diabetic macular edema with intravitreal triamcinolone acetonide injection: functional and anatomical outcomes]. AB - PURPOSE: This prospective study aimed to investigate the effectiveness and safety of intravitreal triamcinolone acetonide (TA) injection in diabetic macular edema unresponsive to an initial argon laser photocoagulation procedure. MATERIAL: and methods: Fifty-six eyes of fifty patients were included in this study. All the eyes had refractory and clinically significant diabetic macular edema with a central macular thickness (CMT) greater than 300 microm. All the eyes were injected 4 mg/0.1 ml TA intravitreally. The main outcome parameters were best corrected visual acuity (BCVA) and CMT. Elevation of intraocular pressure (IOP) and other potential complications were monitored carefully. All the patients were followed at least 9 months. RESULTS: Preinjection mean BCVA was 0.128+/-0.11 and statistically significant improvement in BCVA started in the 1st week and was observed during the first 6 months of the follow-up period. BCVA reached 0.289+/ 0.19 at the 2nd month and decreased gradually to 0.169+/-0.1 at the 9th month. However, clinically significant improvement after TA injection in BCVA (> or =0.2) was observed in 50%, 67.8%, 67.8%, 28.5%, and 12.5% of the eyes in the 1st, 2nd, 3rd, 6th, and 9th months, respectively. The central macular thickness measured by OCT, which was reduced by 45% at the 3rd month, returned nearly to its initial level at the 9th month. High IOP was observed in 35.7% of eyes and appeared between the 1st week and the 2nd month. Other complications were cataract development and progression (7.1%), pseudoendophthalmitis (3.56%), and bacterial endophthalmitis (1.78%). CONCLUSION: Intravitreal TA injection is a relatively safe and beneficial therapeutic method for intractable diabetic macular edema. The recurrence of edema warrants reinjections, even though the risk of complication is higher, especially infectious endophthalmitis, which might be devastating. Further studies should be conducted with newer, slow corticosteroid release methods such as intravitreal devices in the treatment of diabetic macular edema. PMID- 17287670 TI - [Clinical and angiographic characteristics of Bietti's corneoretinal dystrophy: a case study of an 8-year-old girl]. AB - INTRODUCTION: Bietti's crystalline corneoretinal dystrophy is a tapetoretinal degeneration, characterized by the presence of refringent crystals in the corneal limbus and the retina with sclerosis of choroidal vessels. We report the clinical and angiographic features of an 8-year-old girl affected with Bietti's crystalline dystrophy. CASE REPORT: This 8-year-old girl was a sporadic case, born of consanguineous parents. She was referred to our hospital for intermittent strabismus. Her visual acuity was 4/10 at the right eye and 3/10 at the left eye. Biomicroscopy revealed very fine crystals in the limbal area bilaterally. Mydriatic funduscopic examination showed bilateral macular pigment mottling and depigmentation, numerous tiny refractile yellow dots scattered throughout the posterior pole and the mid-periphery associated with diffuse retinal pigment epithelial atrophy and pigment accumulation. Fluorescein angiography revealed retinal pigmentary epithelium alterations. Indocyanine green (Infracyanin) angiography showed areas of choroidal atrophy. The electroretinogram noted a reduction in the number of both types of photoreceptors. COMMENTS: Ophthalmological lesions normally occur between 20 and 30 years of age. The particularity of our case report is the manifestation of the disease at an earlier age (8 years). The progression is characterized by a centrifuge expansion of lesions. PMID- 17287671 TI - [Glaucoma with aniridia and isolated congenital glaucoma in siblings: contribution and limits of genetics]. AB - INTRODUCTION: Congenital glaucoma associated with aniridia and primary congenital glaucoma are regarded as different entities. Indeed, the abnormalities of the angle's structures as well as the genes involved are different. We report the observation of two sisters presenting these two types of glaucoma with particular attention paid to the importance and the difficulty of genetic counseling. OBSERVATIONS: Child L, with no particular family history, had presented bilateral aniridia complicated by bilateral glaucoma since birth. In addition to medical and surgical treatment, general and genetic investigations were undertaken that revealed no abnormalities. No microdeletion of the gene PAX6 responsible for the aniridia was found. Consequently, the genetic advice was in favor of a second pregnancy for this couple. At birth, L's sister also presented bilateral congenital glaucoma, which was isolated, without aniridia. New genetic investigations were carried out but no abnormalities in PAX6, nor in FOXC1 or PITX2 involved in the development of the anterior chamber, were found. Moreover, the haplotypes for aniridia locus AN2 inherited by the two sisters were different, proof that this gene could not be responsible for the glaucoma. DISCUSSION: At L's birth, the hypothesis retained was that she was a sporadic case whose gene mutation could not be identified (which happens in 50% of sporadic cases). The risk for the second pregnancy was negligible, although not null. The primary congenital glaucoma presented by L's sister remains unexplained in the context of aniridia and the role of the PAX6 gene was eliminated. The study of PITX2 and FOXC1 genes involved in anterior segment dysgenesis proved that they were also not involved. Thus, this observation evokes the responsibility of a gene other than PAX6 in aniridia, which could also have a role in isolated congenital glaucoma. CONCLUSION: Analysis of congenital pathologies from a more genetic than clinical point of view seems to progressively break down the barriers established between the various phenotypes of hereditary congenital anomalies. Even if the association of aniridia and primary congenital glaucoma in siblings is reported here for the first time, it does not appear so extraordinary if one considers the complexity of the anterior chamber's development, which involves many genes, most of them still unidentified to date. PMID- 17287672 TI - [Cortisone glaucoma: epidemiological, clinical, and therapeutic study]. AB - INTRODUCTION: Cortisone glaucoma is a secondary glaucoma induced by local or oral steroids used to treat chronic inflammatory diseases. PATIENTS AND METHODS: Retrospective study including 43 eyes of 23 patients (three patients were monophthalmos). We present epidemiological and clinical features with evaluation of functional damage (visual acuity, visual field), and therapeutic results with a follow-up period ranging from 2 to 10 years. RESULTS: Topical steroids were incriminated in 15 of 23 cases (self-medication), whereas general steroids (for chronic diseases) were used by eight patients. Visual function was seriously affected (visual acuity<1/10 in 23/43 eyes at the first visit with pronounced visual field abnormalities). Surgery was necessary in 16 of 43 eyes (deep sclerectomy with or without implant, trabeculectomy). DISCUSSION: Cortisone glaucoma is rather frequent in Tunisia where conjunctival allergy and self medication are common. Young adults are concerned, making it a high surgical risk usually requiring surgical devices such as a T Flux implant. CONCLUSION: Cortisone glaucoma is a serious complication of steroid therapy that usually affects young adults. The disease is usually detected late, explaining the severe functional damage. PMID- 17287673 TI - [Macular hole surgery with and without infracyanine-green-guided removal of the internal limiting membrane]. AB - PURPOSE: To investigate the possibility of an adverse effect of infracyanine guided internal limiting membrane (ILM) removal on functional results of macular hole surgery. PATIENTS AND METHODS: A retrospective study of two consecutive groups of patients operated for macular hole between January 1998 and December 2001. In group 1 (21 patients), no attempt was made to remove the internal limiting membrane. In group 2 (21 patients), the ILM was peeled using infracyanine green (ICG). RESULTS: In group 1, 17 of 21 (81%) macular holes were closed by one surgery and 20 of 21 (95%) in group 2; however, this was not statistically significant. Mean preoperative visual acuity was close to 1 on the Logmar scale in both groups. Postoperative visual acuity was 0.6 in group 1 and 0.5 in group 2: four Snellen lines of improvement in group 1 and five lines in group 2. Postoperative visual acuity was the same or better in 16 of 21 patients in group 1 and in 18 of 21 in group 2. These differences were not statistically significant. Late reopening of the hole was statistically less frequent in group 2. Three cases of atrophic patterns at the level of foveal pigment epithelium were noted in each group as was one case of phototraumatism in group 1. These results were stable after more than 18 months of follow-up. All eyes became pseudophakic. CONCLUSION: In this study, infracyanine-guided removal of the internal limiting membrane did not significantly improve the results of macular hole surgery. No adverse effect of infracyanine on visual function or retinal toxicity was found and late reopening was less frequent. PMID- 17287674 TI - [Hemorrhagic complications of drusen of the optic disk]. AB - INTRODUCTION: The hemorrhagic complications of the optic disk drusen are rare and interesting because of their functional implications, the difficulty of the differential diagnosis and the uncertain pathogeny. MATERIAL: and methods: Retrospective study of 6 cases with a complete general and ophthalmological examination, followed between 2 and 9 years. RESULTS: The average age of the cases was 38.5 years (9-62 years). The visual acuity was slightly affected and reversible in the papillary hemorrhages (1 case), low and partial reversible in the extended hemorrhages (4 cases), severe affected and irreversible in the associations with a choroidal neovascular membrane with macular implications (1 case). We found three types of hemorrhages: papillary (1 case), peripapillary associated with choroidal neovascular membrane in acute (2 cases) and cicatricial stage (1 case), extended subretinal (2 cases). The papillary drusen were profound (4 cases) and superficial (2 cases). Ultrasonography showed the presence of the optic disk drusen in both eyes in all cases. The evolution followed on a period from 2 to 9 years, revealed the resorbtion of the hemorrhages between 3 and 6 months, the reversible visual acuity in the cases without macular implication, and the absence of recidiva or bilateralisation. DISCUSSIONS AND CONCLUSIONS: The authors are presenting a number of clinical cases of papillary drusen complicated with hemorrhages, some of the cases being associated with choroidial neovascular membrane. Because of the clinical appearance, aspects of differential diagnosis with papillary edema of other etiologies are discussed. A role in the pathogeny is attributed to the direct or progressive compression of the retinal vascularisation which can provoke the erosion of the vessels and in some cases the appearance of the choroidal neovascular membrane. The suggested therapy is medical, surgical, or by photocoagulation, but the results are contradictory. PMID- 17287675 TI - [Ocular biometric values of the black African patient and theoretical consideration of the role of these values in various pathologies: analysis of 325 eyes]. AB - INTRODUCTION: The international literature seldom refers to eye measurements of the black African patient. Therefore, the various patterns where biometry elements are used as constituents deserve reconsideration as they may not correspond to the eye of the black patient of our region. This study provides true measurements for the black African patient in Ivory Coast. It also establishes hypotheses by extrapolating the role of measurements in pathologies such as glaucoma. MATERIAL: and method: The study included 325 eyes of 217 male and female patients. All the patients underwent ocular keratometrics and echo biometrics to measure the depth of the anterior chamber, the width of the lens, and the total axial length with the ultrascan biometer using the contact method in A echometrics. RESULTS: The mean keratometry in women was significantly higher than in men (43.99 +/- 1.62 diopters vs 43.46 +/- 1.45 diopters). The anterior chamber was deeper in men (2.69 mm +/- 0.54 vs 2.53 mm +/- 0.48). The men's eyes were significantly longer, with an axial length of 23.26 mm +/- 1.07 vs 22.56 mm +/- 0.90. CONCLUSION: Significant biometric differences between men's and women's eyes, on the one hand, and between black African and white patients' eyes, on the other hand, can be observed. The reasons for these differences are several: they are natural, socioeconomic, and technical. If standard implant of a different power for black and white patients can be imagined, can we also infer that the biometrics of a black African patient predisposes him to a disorder such as glaucoma more than a white patient? Further in-depth studies could provide an answer to this question. PMID- 17287676 TI - [Ocular surface investigations in dry eye]. AB - Dry eye is a complex clinicopathological entity involving tear film, lacrimal glands, eyelids, and a wide spectrum of ocular surface cells, including epithelial, inflammatory, immune, and goblet cells. From the tightly regulated lacrimal film functions and structure, a large variety of investigations have been developed, including tear meniscus measurements, fluorophotometry, meibometry, interference pattern analysis, evaporation rate, tear osmolarity, and thermography. Dry eye conditions also interfere with the ocular surface, causing corneal irregularities that may be explored using the techniques of videokeratography and in vivo confocal microscopy, or optical impairment, as confirmed by aberrometry. At the level of ocular surface cells, impression cytology remains a standard for assessing cell alterations. It has greatly benefited from new confocal microscopy, molecular biology, and flow cytometry techniques. Biological assessment of tear proteins or other mediators is also useful. Major limits should be acknowledged, however, such as technical issues in tear film collection, especially in dry eyes, and the lack of standardization of most measurements. Tear osmolarity, electrophoresis, and dosage of normal tear proteins, such as lysozyme or lactoferrin, remain the most useful tests. Finally, some extraocular explorations such as accessory gland biopsy or serum antinuclear antibody dosage may be useful for assessing the diagnosis of Sjogren's syndrome. PMID- 17287677 TI - [Macroscopic and histological data in the prognosis of malignant choroidal melanoma]. AB - The macroscopic study of choroidal melanoma gives information on tumor extension and tumor size, which help in determining the prognosis and in making the therapeutic choice. Numerous microscopic changes observed in melanomas are also important in the prognosis. However, the number of available histologic specimens has dramatically decreased since the generalized use of conservative radiation treatment. Except in cases of enucleation or choroidectomy, the histologic criteria to establish the prognosis are not available in many cases and cannot be used for wide-range statistical studies. PMID- 17287678 TI - [Eye anterior segment envenomation following a hymenopteran corneal sting]. PMID- 17287679 TI - Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions. Clinical and angiographic results of the ENDEAVOR II Trial. AB - AIM: The use of the Endeavor stent might reduce restenosis and stent thrombosis at 9 months. METHODS: Patients (n =1,197) treated for single coronary artery stenosis were enrolled in a prospective, randomized, double-blind study and randomly assigned to receive the Endeavor zotarolimus-eluting phosphorylcholine polymer-coated stent (n= 598) or the same bare metal stent but without the drug or the polymer coating (n=599). RESULTS: The 2 groups were well matched in baseline characteristics. Diabetes was present in 20.1% of patients; the mean reference vessel diameter was 2.75 mm; and the mean lesion length was 14.2 mm. The primary end point of target vessel failure at 9 months was reduced from 15.1% with the bare metal stent to 7.9% with the Endeavor (P=0.0001), and the rate of major adverse cardiac events was reduced from 14.4% with the bare metal stent to 7.3% with the Endeavor (P=0.0001). Target lesion revascularization was 4.6% with Endeavor compared with 11.8% with the bare metal stent (P=0.0001). The rate of stent thrombosis was 0.5% with the Endeavor, which was not significantly different from 1.2% with the bare metal stent. In 531 patients submitted to angiographic follow-up, late loss was reduced from 1.03+/-0.58 to 0.61+/-0.46 (P<0.001) in stent and from 0.72+/-0.61 to 0.36+/-0.46 (P<0.001) in segment. The rate of in-segment restenosis was reduced from 35% to 13.2% with Endeavor (P<0.0001). There was no excessive edge stenosis, aneurysm formation, or late acquired malposition by intravascular ultrasound imaging. Differences in clinical outcome were maintained at 12 and 24 months (P<0.0001). CONCLUSIONS: Compared with bare metal stents, the Endeavor stent is safe and reduces the rates of clinical and angiographic restenosis at 9, 12, and 24 months. PMID- 17287680 TI - Carotid angioplasty and stenting under protection. State of the art. AB - A carotid stenosis is responsible for about 30% of strokes occurring. Carotid endarterectomy (CEA) is considered to be the gold standard treatment of a carotid stenosis. Carotid angioplasty and stenting (CAS) is emerging as a new alternative treatment for a carotid artery stenosis, but the risk of neurological complications and brain embolism remain the major drawback to this procedure. So as to reduce the risk, we need: good indications, good patient and lesion selection; correct techniques; brain protection devices (cerebral protection devices should be routinely used and are mandatory for any procedure. Three types of protection devices are available: filters are the most commonly used. Nevertheless, all protection devices have limitations and cannot prevent from embolic events. However neurological complications can be reduced by 60%. New protection devices will be discussed); good choice of the stent and correct implantation (all stents are not equivalent and have different geometrical effects); pharmacological adjuncts; good team. Indications are well accepted for high-risk patients and recent studies have shown that CAS has superior short-term outcomes than CEA in this group of patients. Indications for low-risk and asymptomatic patients are controversial. New selection criteria have to be discussed. But there are enough reported data to conclude that CAS is also not inferior to CEA in low-risk and asymptomatic patients. In our series of 844 procedures, without protection (n = 187) 30-day death and stroke rate was 3.7% and with protection (n = 657) 1% (1.3% for symptomatic patients, 0.9% for asymptomatic patients, 1.4% in high-risk patients, 0.4% in low-risk patients). CAS under protection is the standard of care and is maybe becoming the gold standard treatment of a carotid stenosis at least in some subgroups of patients. PMID- 17287681 TI - Percutaneous coronary intervention of bifurcation coronary disease. AB - Bifurcation coronary artery disease is a frequent problem faced by interventional cardiologists and it affects approximately 15-20% of patients undergoing percutaneous coronary intervention (PCI). The application of drug-eluting stents (DES) technology to prevent restenosis after PCI represents one of the success stories in cardiology, but DES have not resolved the bifurcation PCI challenge. Bifurcation PCI remains associated with higher procedural failure and worse outcomes compared with PCI of non-bifurcated lesions even in DES era. A dependable strategy for PCI of bifurcation lesions has yet to be established, which is likely due to the paucity of studies evaluating the anatomical intricacies of the bifurcation as well as the lack of large scale randomized therapeutic trials. Further, bifurcation has many anatomical variants and it is unlike that one technique will fit all. Currently, we are left with the option of a tailor-made strategy for each patient and bifurcation anatomy and make the most of the limited evidence available to support our therapeutic decisions. In this review, we attempted to describe the current understanding of bifurcation anatomy and corresponding PCI strategies. PMID- 17287682 TI - Acute myocardial infarction interventional procedures: primary percutaneous coronary intervention versus facilitated percutaneous coronary intervention, rescue angioplasty, rescue excimer laser. AB - ST-elevation myocardial infarction is due to the occlusion of a coronary artery, mainly due to a rupture of an atherosclerotic plaque with superimposed thrombosis. The main therapeutic goal is to restore the blood flow within the culprit artery as quickly as possible. In this review we discussed the several approaches which have been employed to reach this target. Primary percutaneous coronary intervention (PCI) is considered the best treatment option, as it is associated to lower in-hospital mortality, reduced risk of reinfarction and stroke, lower rate of intracranial bleeding and ventricular rupture from myocardial hemorrhage compared with fibrinolytic therapy. Also, it is superior to facilitated PCI, i.e. immediate planned PCI after i.v. thrombolytic therapy administration, because of lower mortality, reinfarction rate, strokes and bleedings. Rescue PCI after failed thrombolysis was associated with a reduction of early severe heart failure and improved survival at 1 year, in patients with moderate to large infarctions, compared to conservative medical therapy, in a pooled analysis of 9 randomized trials, carried out in the balloon era. Also in the stent era, a meta-analysis of 5 randomized trials found a significant 36% reduction in the risk of 30-day mortality, a trend to lower risk of heart failure, although a marginally increased risk of thromboembolic stroke, in the rescue PCI arm. However, rescue PCI is not associated with a better long-term clinical outcome. Laser thrombectomy before PCI could be a useful additional strategy which might be compared to standard stenting in future randomized studies. PMID- 17287683 TI - Advances in the percutaneous treatment of aortic and mitral valve disease. AB - The healthcare burden of valvular heart disease continues to increase as our population ages. Because of advances in operative techniques and cardiac anesthesiology, surgery has excellent safety and durability for many patients, and surgery remains the gold standard for treating valvular heart disease. Because many patients have comorbidities that increase operative risk, interest in catheter-based valve repair and replacement has grown. Early human experience with aortic stent-valve prostheses has been quite encouraging. For mitral regurgitation, percutaneous annuloplasty and leaflet repair are being developed by numerous companies, and early human studies have demonstrated feasibility of percutaneous repair. Continuing advances in technology and experience promise to expand the role of percutaneous repair and replacement in the treatment of valvular heart disease. Ongoing trials will help define long-term durability and safety, along with appropriate patient selection for percutaneous treatment. PMID- 17287684 TI - Integration of computed tomographic coronary angiography into the invasive laboratory and into interventional coronary procedures. AB - Computed tomographic coronary angiography (CTA) has rapidly evolved to a level where it can be used not only for the diagnosis or exclusion of coronary artery disease, but also to a stage at which the value of CTA derived images in the catheterization laboratory during invasive procedures is under examination. This review will examine the possible role of CTA in selection of patients for invasive coronary angiography (ICA), in the planning of diagnostic ICA in patients who have undergone previous revascularization and the role of CTA in planning percutaneous interventional and surgical procedures. PMID- 17287685 TI - Usefulness of cardiac magnetic resonance imaging for coronary artery disease detection. AB - Cardiac magnetic resonance imaging (cMRI) is a promising non-invasive technique to assess the presence of coronary artery disease (CAD), which is free of ionizing radiation and iodine contrast. cMRI can detect CAD by angiographic methods or indirectly by perfusion stress techniques. While coronary angiography by cMRI remains limited to research protocols, stress perfusion cMRI is currently being applied worldwide in the clinical setting. Studies have shown good correlation between adenosine-induced stress myocardial perfusion cMRI and single photon-emission computed tomography or positron emission tomography to detect CAD. Quantitative methods to analyze cMRI perfusion data have been developed in an attempt to provide a more objective imaging interpretation. Standardization of such quantitative methods, with minimal operator dependency, would be useful for clinical and research applications. Myocardial perfusion reserve (MPR), calculated using Fermi deconvolution technique, has been compared with well established anatomical and physiological CAD detection techniques. MPR appears to be the most accurate quantitative index to detect anatomical and hemodynamically significant CAD. Beyond physiological assessment of CAD, cMRI provides information regarding regional and global left ventricular function and morphology, myocardial infarction size, transmurality and viability. Such comprehensive information would require the performance of multiple tests if other modalities were used. This article describes current applications of cMRI for evaluation of patients with CAD. PMID- 17287686 TI - Clinical implications, technique and outcome of endovascular treatment of renal artery stenosis. AB - Renal artery stenosis (RAS) may cause or deteriorate arterial hypertension and/or renal insufficiency. Moreover, RAS seems to affect structural heart disease. Technical improvements of diagnostic and interventional endovascular tools have led to a more widespread use of endoluminal renal artery revascularization and extension of the indications for this type of therapy. Since the first renal artery angioplasties performed by Mahler and Gruntzig in 1978, mostly single center studies have reported in the majority of patients beneficial effects of percutaneous transluminal renal angioplasty, and since the early 1990's of stenting RAS. Due to reports upon post procedural impairment of renal function in a reasonable number of patients, the role of protection devices has been raised recently. This article summarizes the current technique of endovascular treatment of RAS and the clinical impact on blood pressure control, renal function, and structural heart disease. The results discussed are based mainly on registry data because randomized studies comparing stent-supported angioplasty with best medical therapy are still missing. PMID- 17287687 TI - Endovascular treatment of femoro-popliteal obstructive disease. AB - The systemic nature of vascular atherosclerosis is beginning to involve not only the angiologists and the vascular surgeons, but also the clinical and the invasive cardiologists. Femoral occlusive disease is one of the most challenging field due to the particular anatomical morphology of the femoral arterial wall that is prone to obstructive disease and high restenosis rate after percutaneous revascularization. Acute and chronic arterial diseases are the main clinical scenario involving femoral vessels. Percutaneous techniques include endoluminal recanalization, subintimal recanalization, stent implantation, mechanical and rheolytic thrombectomy, laser angioplasty, and cryoplasty. In this review the authors propose an overview and an update of the most recent advances in techniques and results in the field of endovascular treatment of femoral artery occlusive disease. PMID- 17287688 TI - [The Nissen-Rossetti fundoplication: outcomes and lessons learned in 35 years experience with the same procedure]. AB - AIM: The total fundoplication achieves most effective long-term control of gastro esophageal reflux disease (GERD). However, the different types of total fundoplication lead to heterogeneous outcomes. In 1972, we standardized a personally modified Nissen-Rossetti which includes the routine use of intraoperative manometry and endoscopy to calibrate and check the wrap. This paper aims to describe the technical details and the outcomes of this procedure adopted since 35 years without modifications as a unique procedure to treat all patients with GERD. METHODS: The study population consisted of all patients affected by GERD who underwent laparoscopic Nissen-Rossetti fundoplication by a single surgeon with one year minimum of follow-up. Technical details of the procedure and data from clinical and instrumental follow-up are described. RESULTS: Clinical follow-up (median 83 months; range 1-13 years) was achieved in 96% of the patients. Ninety-two percent of the patients were satisfied of the procedure and would undergo the same operation. At 12 months, lower esophageal sphincter pressure increased to 27+/-5 mmHg (P<0.05), 24-h monitoring became negative in 91.6% of the patients (P<0.05). DeMeester score was 4.1+/-0.7 (P <0.05). CONCLUSIONS: The laparoscopic Nissen-Rossetti fundoplication with the routine use of the intraoperative manometry and endoscopy, adopted as a unique procedure to treat all the patients with GERD, achieved long-term patient satisfaction in the great majority of the cases. Meticulous preoperative investigation together with a correct surgical technique are needed in securing these results. PMID- 17287689 TI - A retrospective review of the histopathology and clinicopathologic correlates of appendices removed from patients of acute appendicitis. AB - AIM: Appendicitis is the most common intra-abdominal condition requiring emergency surgery, with a life time risk of about 6%. Although considerable data are available in the literature regarding the histopathology of appendicectomy specimens, such information from the Indian subcontinent remains unreported. METHODS: A total of 348 consecutive appendices removed because of clinical suspicion of acute appendicitis were selected. Three sections from each specimen were submitted for histopathology. Histopathologic acute appendicitis if present was further classified into 3 subcategories. A retrospective analysis was performed on all these specimens. RESULTS: The male female ratio was 2.6:1 with highest number of cases in the age group 21-30 years; 282 specimens out of 348 showed features consistent with acute appendicitis with an overall higher occurrence in males. Statistically significant association was obtained between perforation and male sex, older age and acute suppurative appendicitis. CONCLUSIONS: Present study shows that acute appendicitis in India is a disease of young males. The negative appendicectomy rate is about 10.9%. On further subclassification of acute appendicitis, uncomplicated acute appendicitis seems to be the most common followed by acute suppurative appendicitis. PMID- 17287690 TI - [Postoperative acute pancreatitis: our experience and review of the literature]. AB - AIM: Acute postoperative pancreatitis is a rare event, but, at the same time, it represents one of the most frightening complications, because it is associated with high mortality risk. METHODS: From January 1985 to December 2005, we observed 30 cases (12 males, 18 females) of acute postoperative pancreatitis. Twenty cases of low and medium gravity have been treated with only medical therapy, 10 cases, instead, have requested surgical therapy (necrosectomy and application of abdominal drains in 7 cases, necrosectomy and ileostomy in 1 case, necrosectomy and colostomy in 1 case, ligation of pancreatic vessels in 1 case of haemorrhagic pancreatitis). RESULTS: In the form of low and medium gravity, fast and pharmacological support (somatostatin and gabexate mesilate) are enough to resolve the event. In the form of high gravity the early surgical treatment has represented the clinical solution in 7 patients, while 3 others patients have died for septic and metabolic complication. CONCLUSIONS: Still today acute postoperative pancreatitis represents a frightening complication associated with high mortality risk that the surgeon has to treat with great care to avoid each bilio-pancreatic injury. PMID- 17287691 TI - [Abdominal tuberculosis: clinical features, diagnosis and role of surgery]. AB - AIM: Nowadays the incidence of tuberculosis is increasing in some population groups (subjects immigrated from developing countries, affected from HIV infection, or undergoing immunosuppressive therapy) and to the development of multidrug-resistance. The clinical manifestations, routine laboratory and radiographic analyses of abdominal tuberculosis are nonspecific and surgery plays a fundamental role because 25-75% of such patients are operated. METHODS: Six patients, 4 male and 2 female (age 23-62 years) underwent laparotomy or laparoscopy. Five patients were not European, 1 was Italian. The surgical indications were: intestinal occlusion in 3 patients; perforation in 1 patient; peritonitis in 2 patients. RESULTS: The most frequent clinical manifestations were pyrexia, weight loss, anemia, ascites. Chest X-ray was normal in all patients. All patients were found ARB-negative in sputum and in ascitic fluid, while 1 was positive to culture of sputum and 3 of ascitic fluid. In all patients histopathologic examination showed typical findings of tuberculosis. CONCLUSIONS: The surgical indication is made for diagnostic aim or due to the presence of complications. Laparoscopy is the gold standard in the diagnosis,since it allows whole exploration of abdomen and taking of sample for biopsy and ascitic fluid to find micobacterium. In fact, abdominal tuberculosis is a paucibacillar disease and rarely it is possible to demonstrate the direct presence of M. Tuberculosis, but nowadays the methods of the genome amplification allow to demonstrate the sequence of the chromosomial DNA of M. Tuberculosis from small fragments of bioptic material. PMID- 17287692 TI - [Primary breast lymphoma: case report and review of literature]. AB - Primary non-Hodgkin's lymphoma of the breast is a rare entity representing 0.04 0.5% of all malignant female breast tumors, less than 1% of all patients with non Hodgkin lymphoma and approximately 1.7-2.2% of all patients with extranodal non Hodgkin lymphomas. A 75 years old patient presented with masses in the lateral part of the left breast for 6 weeks. Ultrasound detected 3 masses suggesting fibroadenomas while mammography set the suspicion of breast multicentric carcinoma. Fine needle aspiration cytology of one mass showed low grade lymphoma subsequently confirmed with histopathology which diagnosed extranodal non-Hodgkin lymphoma MALT type CD 20+/CD 79a+/CD 3-/Bcl 2- and index of proliferation Ki 67=30% (stage IE). Primary non-Hodgkin lymphomas of the breast, though rare, should be considered in the differential diagnosis of breast malignancies. At present, a standard treatment doesn't exist yet; low grade lymphomas should be managed with excision biopsy and/or local radiation therapy, while high grade lymphomas should be managed with chemotherapy in association with radiation therapy. PMID- 17287693 TI - Extralobar pulmonary sequestration showing high CA 19-19 levels. AB - We report a case of 40 year-old woman with left thoracic pain who was diagnosed as having a cystic mass located posteriorly at the basis of the left pleural cavity. The preoperative serum CA 19-9 level was increased (2 900 IU/mL). Further investigations did not find neoplastic lesions in the gastrointestinal tract. The intraoperative finding of an anomalous systemic arterial supply to the mass suggested the diagnosis of extralobar sequestration, confirmed at the histopathological examination. The association between pulmonary sequestration and increased tumor markers levels is overlooked in western literature, but it is often reported by many Japanese authors. This case report would underline the practical usefulness for preoperative diagnosis of pulmonary sequestration, when the CT-scan does not demonstrated an anomalous systemic vessel. The common embryogenic origin of both respiratory and digestive apparatus can explain the increased levels of tumor markers such as CA 19-9 and carcinoembryonic antigen in bronchogenic cyst, intestinal duplication and pulmonary sequestration. PMID- 17287694 TI - Heart lymphoma 6 years after a prosthetic ascending aorta replacement: related or unrelated? AB - An highly malignant B-cell lymphoma developed acutely 6 years after replacement of the aortic root with a Dacron prosthesis, involving the heart and the adjacent mediastinum. Rapid clinical deterioration and absence of early histological confirmation led to exploratory unsuccessful surgery. This case illustrates the rapid evolution of some of these tumours and raises again the hypothesis of the carcinogenic potential of Dacron material. PMID- 17287695 TI - Cholecystoduodenal fistula in a nonagenarian. Can laparotomy play a role in the era of laparoscopic? Case report. AB - Cholecystoduodenal fistula, a rare complication of biliary lithiasis, occurs in 0.5% to 3% of patients affected by cholelithiasis. Diagnosis is not easy and is usually incidental at surgery. The literature guidelines call for a laparoscopic approach to treating these patients; here, however, we report a case of a very elderly patient in which, among other reasons, open surgery was the treatment of choice to decrease morbidity and mortality. PMID- 17287696 TI - Acute gastric anisakiasis: an Italian experience. AB - Anisakidosis is a parasitic disease of the human gastrointestinal tract caused by ingestion of larvae of marine nematodes such as Anisakis spp. or, rarely, Pseudoterranova spp., present in raw or undercooked fish. We report the first series of gastric Anisakis infection (anisakiasis) from a single centre in Italy. In our department, we observed 3 cases, all in women who were urgently hospitalized following intense epigastric pain and vomiting, developed after the ingestion of raw fish. The patients underwent urgent gastroscopy within a few hours. In each, a worm was extracted from the gastric mucosa by means of biopsy forceps. This was followed by prompt clinical improvement. The worm was identified by its macroscopic and microscopic characteristics as an Anisakis spp. larva (L3). In 2 cases, laboratory tests revealed marked leukocytosis and eosinophilia in the peripheral blood 3-4 days after ingestion of the raw fish. The diagnosis of anisakiasis can be made by endoscopy, radiology and abdominal ultrasound, but is often made only at surgery. In the gastric form of the disease, urgent gastroscopy has both a diagnostic and a therapeutic role, because the worm can be removed by means of biopsy forceps. PMID- 17287697 TI - [Anastomotic configuration as a risk factor in the recurring onset after intestinal resection for Crohn's disease: our point of view]. AB - Crohn's disease is an inflammatory chronic intestinal disease characterized of an high level of postoperative recurrence. Actually surgical treatment is not decisive; patients can undergo several operations during their lives, running the risk of coming up against the syndrome of short bowel. The main disease frequently appears in the segment ileo-caecal, while the site more often affected by the recurrence seems to be the stump close to the anastomosis. General, local and not specific factors should influence the recurrence level. Among the general factors, cigarette smoking would have a leading role in the recurrences onset. Giving up smoking and a treatment with 5-ASA (amino-salicylic acid) help to reduce the risk of Crohn's recurrences after surgery. During the treatment of this pathology the wide intestinal resections are not justified because the anastomotic recurrence after resection seems to be influenced not by the presence of remaining lesions but by the type of realized anastomosis. Although they disagree about the type of anastomosis to adopt, the authors agree identifying the anastomotic stenosis as the main factor which determines the recurrences. Stenosis, in fact, determining fecal stasis and, therefore, the increase of the pressure at the intestinal wall level, causes ischemia of this same wall. Ischemia puts up the risk of fistulas and anastomotic dehiscence. The mechanical or manual ileo-colic side-to-side anastomosis, assuring a wide lumen, drops to the minimum the risk of stenosis compared with the end-to-end and end-to-side configurations. And then, the side-to-side ileo-colic anastomosis avoiding the intestinal compartmentation between ileo and colon, guarantees less reflow in the small bowel of bacteria and colic metabolite. In this way the inflammatory process which brings to the fresh outbreak of the disease on the mucosa of the near anastomotic head faints. In the light of this thesis, most of the authors, including the writer, agree about making the side-to-side anastomoses in the intestinal resections for the Crohn's disease. PMID- 17287698 TI - [Late complication after colon self-expandable metal stent placement: a case report]. AB - Treatment of acute colorectal malignant obstruction, by using self-expandable metallic stents is useful for both palliative and decompressive therapy before the final surgical treatment. In this case, the patient may be benefit from a period of medical optimization prior to undergoing planned surgical resection by a colorectal surgeon. This is a minimally invasive procedure, relatively safe, which obviates the need for colostomy for evacuation relieving physical and psychological burden and contributing the improvement of quality of life. Furthermore, this method also has the advantage of being cost-effective. The previous experience in the benign biliary stenosis allowed the extension of using the metallic stents also for the treatment of benign colorectal diseases (diverticular occlusion, anastomotic strictures, colonic endometriosis). Complications of colon self-expandable metallic stents placement may occur during the procedure and soon after placement (early complications) or, rarely, late after insertion (late complications). These include bleeding, re-obstruction, pain, tenesmus, stent migration, and perforation. The authors report a case of an 81 year-old woman with inoperable rectal carcinoma with liver metastasis who underwent palliative treatment of self-expanding metallic stent endoscopic placement. One month later, the patient presented with acute abdomen at Accidents and Emergencies Department. The diagnosis was a late rectosigmoid junction perforation by stent placement. PMID- 17287699 TI - [Use of Tachosil in splenectomy in patients with clotting and blood composition disorders]. AB - Splenectomy in patients suffering from onco-haematological conditions presents clotting-related problems which make correct haemostasis more difficult. Using operative haemostasis during splenectomy for onco-haematological conditions as a starting point, the authors report their personal clinical experience of the use of Tachosil, comparing it with other similar products and drawing some personal CONCLUSIONS: To complete their reflexions on clotting problems during splenectomy in the course of onco-haematological diseases, the comparison with its use in oncological pathologies in other parenchymas, such as the kidney and liver, which also present operative haemostatic difficulties of a technical nature, is pointed out and the soundness of the results indicated. The cases of 3 patients suffering from severe clotting disturbances and treated with splenectomy and 1 patient suffering from clear cell renal carcinoma and subjected to nephrectomy in which Tachosil was used as an aid to haemostasis are reported. In the light of these cases, it can be stated that, albeit with the persistence of difficulties related to the changed clotting capacities resulting from the basic disease, the use of Tachosil has proved effective as an aid in haemostasis and suggests the validity of its use in elective and emergency splenectomy, in these types of patient. PMID- 17287700 TI - Successful transplantation of an eighty-one-year-old liver with proper hepatic artery aneurysm. PMID- 17287702 TI - Augmentation of keratinized gingiva through bilaminar connective tissue grafts: a comparison between two techniques. AB - AIM: A mucogingival deficiency is considered a potential risk factor for periodontal disease. In particular, mucogingival deficiency can lead to gingival recession, which is a pathological entity per se, due to the increased risk for dental hypersensitivity and root caries. The aim of this study was to evaluate and compare 2 bilaminar grafting techniques normally employed to achieve root coverage. METHODS: Thirty-five patients were divided into 2 groups. Group 1 included 19 patients with 49 gingival recessions treated by Nelson technique (as modified by Harris), while group 2 included 15 patients with 40 recessions treated by Langer technique. Clinical evaluation was performed at preoperative level (T0), after 1 month (T1) and after 1 year (T2). Statistical analysis was performed by means of Friedmann and Wilcoxon test and U-Mann-Whitney test. RESULTS: The statistical analysis did not reveal any significant difference between groups, both in terms of percentage of root coverage and of width of keratinizaed gingiva gain. A significant difference was only observed within each group, for the amount of keratinized gingiva at T1 vs T0 and at T2 vs T1. CONCLUSIONS: This study did not show any statistical difference between the Nelson and the Langer technique as to root coverage and gain in keratinized gingiva. PMID- 17287703 TI - The effect of levosulpiride in burning mouth syndrome. AB - AIM: This paper evaluated the efficacy of the systemic administration of levosulpiride, an antipsychotic and antidepressant drug, in the management of burning mouth syndrome. METHODS: Forty-four subjects suffering from idiopathic burning mouth syndrome were enrolled in the study. Patients underwent a thorough clinical examination, including salivary flow rate measurements, laboratory tests (complete blood cell counts, blood glucose levels, serum iron and transferrin levels, serum vitamin B(12), and folate levels), patch tests for contact allergy to denture materials, and isolation of Candida species from oral mucosal scrapes. Oral symptoms before and after treatment were assessed using a visual analogue scale. All the patients used systemic levosulpiride (100 mg/daily) for 8 weeks. RESULTS: Of the 39 patients who completed the protocol, none reported complete remission of the oral burning sensation. However, 28 patients reported at least some improvement, and these patients had had oral symptoms for significantly less time than those who reported no improvement. CONCLUSIONS: These preliminary data suggest that levosulpiride is more effective in patients who have recently developed burning/stinging oral sensation. PMID- 17287704 TI - Effect of superpulsed laser irradiation on bone formation in a human osteoblast like cell line. AB - AIM: The effect superpulsed of low-level laser therapy (SLLLT) on bone regeneration has been the focus of recent research. This preliminary study investigated the effect of superpulsed laser irradiation on proliferation and bone formation in human osteoblast-like cells MG-63. METHODS: Human osteoblast like cells MG-63 were exposed every 24 h to superpulsed low-level laser produced by the device Lumix 2 HFPL Dental (Fisioline s.n.c., Verduno, Cuneo, Italy); the experimental protocol comprised 4 days of treatment. At each experimental time, cell proliferation and some markers of osteoblast activity were evaluated. RESULTS: Numbers of laser-treated cells increased starting from day 2 of treatment. The ability of SLLLT irradiation to stimulate bone production was evaluated by determining the expression of osteocalcin and alkaline phosphatase, proteins involved in calcium nodule formation. These proteins increased markedly after 3 days of laser treatment. CONCLUSIONS: These preliminary results show that repeated SLLLT irradiation stimulates cell proliferation in human osteoblast-like cells and, importantly, increases the expression of proteins essential for bone formation. PMID- 17287705 TI - Root resorption and orthodontic treatment. Review of the literature. AB - The aim of this paper was to provide a systematic review of the literature on the root resorption caused by orthodontic treatment. Original papers on this subject, published in English from January 2000 until December 2005, were located in the MEDLINE/PubMed database. Other sources were taken from the references of the selected papers. Root resorption is the most common sequela of the orthodontic treatment. It is an inflammatory process that leads to an ischemic necrosis localized in the periodontal ligament when the orthodontic force is applied. The onset and progression of root resorption are associated with risk factors related to the orthodontic treatment such as the duration of treatment, the magnitude of the force applied, the direction of the tooth movement, the method of force application (continuous versus intermittent), the orthodontic movement. Patient related risk factors are the individual susceptibility on a genetic basis, some systemic diseases, anomalies in root morphology, dental trauma, and previous endodontic treatment. The prevention of root resorption during the orthodontic treatment may be performed controlling the risk factors. The periodic radiographic control during the treatment is necessary in order to detect the occurrence of root damages and quickly reassess the treatment goals. PMID- 17287706 TI - Esthetics and implantology: medico-legal aspects. AB - In recent years the high number of malpractice lawsuits in dentistry has attracted closer attention of dental practitioners to its medico-legal aspects. Implantology, in particular, presents many points of medico-legal concern connected with the difficulties inherent to dental procedures and objectives (both functional and esthetic), as well as full patient collaboration as an essential part of successful treatment. An accurate assessment of each case by the clinician is fundamental, especially in circumstances where esthetic considerations are preponderant as, for instance, in the frontal sectors. In such cases, the options of implantology or of a traditional fixed prosthesis need to be carefully weighed in light of the patient's anatomic condition. The patient should therefore receive complete information and be made fully aware of the risk of treatment failure, as well as possible complications, limits to the procedures, and the fact that successful outcome will also depend on her/his scrupulous observance of the practitioner's instructions. In short, the aim is to make the patient an active ''accomplice'' in treatment. To this end, the use of an extremely detailed information leaflet is strongly advised; after careful clarification of any doubts the patient may have, the patient's written informed consent should be obtained. Nevertheless, there is the risk that excessive intrusion of bureaucracy into medical procedures in defence of the practitioner against malpractice suits may hinder the principal aim of traditional medicine, i.e. to provide the best care for the patient through mutual trust fostered within the doctor-patient relationship. PMID- 17287707 TI - Retrieval of blade implants with piezosurgery: two clinical cases. AB - In this work an ultrasound device was used to perform an ostectomy for the removal of blade implants in order to save as much bone tissue as possible, so that root form implants might later be inserted. Two patients underwent surgery for the removal of two blade implants (one maxillary, the other mandibular) that were no longer functional. The peri-implant ostectomy was carried out with a piezoelectric surgery device. The instrument demonstrated to be effective and precise during ostectomy, providing an extremely thin cutting line. During the course of the operation and at controls after 7 and 30 days, patients did not show any relevant complications and both still had sufficient alveolar bone to be treated with root form implants. The piezosurgery device proved to be an effective instrument in interventions requiring a significant saving of bone tissue, extreme precision in cutting, and respect of soft tissues. PMID- 17287708 TI - Bone grafting with platelet-rich plasma in alveolar cleft. Case report. AB - Bone grafting of the alveolus has become an essential part of the contemporary surgical management of oral clefts. The benefits of this procedure are the stabilization of the maxillary arch, elimination of oronasal fistulae, the reconstruction of the soft tissue nasal base support, creation of bony support for subsequent tooth eruption or, when they are not present or not preserved, for implants application. The authors show a case of bone grafting with the aid of platelet-rich plasma (PRP). Because of the difficulties due to the oral cleft and to its surgical reparation (big size of bone defect, hard scars and sclerotic soft tissue) the authors decided to add PRP to a bone graft taken from the chin. PRP contains a high concentration of growth factors and is able to stimulate both wound and bone regeneration. Infact, the authors have observed very good results both in bone integration and in soft tissue reparation. PMID- 17287709 TI - Traumatic ulcerative granuloma with stromal eosinophilia of the oral mucosa: histological and immunohistochemical analysis of three cases. AB - Traumatic ulcerative granuloma with stromal eosinophilia is an ulcerated oral lesion which pathogenesis is still unclear. Clinically, this disease is characterized by the presence of chronic ulcerative lesions with elevated and indurated borders in the oral mucosa. It usually develops rapidly and persists for several weeks or months, it presents mainly on the tongue but other areas such as gingival, cheek and vestibular mucosa may also be involved. We report three cases showing their clinical, histological and immunohistochemical analysis. In this study the authors underline the importance of a correct differential diagnosis and monitoring of these patients in order to prevent the development of possible serious complications. PMID- 17287712 TI - Unintentional poisoning deaths--United States, 1999-2004. AB - In 2004, poisoning was second only to motor-vehicle crashes as a cause of death from unintentional injury in the United States . Nearly all poisoning deaths in the United States are attributed to drugs, and most drug poisonings result from the abuse of prescription and illegal drugs. Previous reports have indicated a substantial increase in unintentional poisoning mortality during the 1980s and 1990s. To further examine this trend, CDC analyzed the most current data from the National Vital Statistics System. This report summarizes the results of that analysis, which determined that poisoning mortality rates in the United States increased each year from 1999 to 2004, rising 62.5% during the 5-year period. The largest increases were among females (103.0%), whites (75.8%), persons living in the southern United States (113.6%), and persons aged 15-24 years (113.3%). Larger rate increases occurred in states with mostly rural populations. Rates for drug poisoning deaths increased 68.3%, and mortality rates for poisonings by other substances increased 1.3%. The largest increases were in the "other and unspecified," psychotherapeutic, and narcotic drug categories. The results suggest that more aggressive regulatory, educational, and treatment measures are necessary to address the increase in fatal drug overdoses. PMID- 17287713 TI - Foodborne botulism from home-prepared fermented tofu--California, 2006. AB - In December 2006, the Orange County Health Care Agency (OCHCA) and California Department of Health Services (CDHS) were notified of two potential cases of foodborne botulism in an older Asian couple. This report summarizes the subsequent investigation, which identified home-prepared fermented tofu (soybean curd) as the source. The public should be aware of the risk for botulism when preparing fermented tofu at home. PMID- 17287714 TI - Prevalence of autism spectrum disorders--autism and developmental disabilities monitoring network, six sites, United States, 2000. AB - PROBLEM/CONDITION: Data from a population-based, multisite surveillance network were used to determine the prevalence of children aged 8 years with autism spectrum disorder (ASD) in six areas of the United States and to describe the characteristics of these children. REPORTING PERIOD: 2000. METHODS: Children aged 8 years were identified as having an ASD through screening and abstraction of evaluation records at multiple sources, with clinician review of abstracted records to determine case status. Children whose parent(s) or legal guardian(s) resided in one of the six surveillance areas during 2000 and whose records documented behaviors consistent with the American Psychiatric Association's criteria for diagnosing 1) autistic disorder, 2) pervasive developmental disorder not otherwise specified, or 3) Asperger disorder were classified as having an ASD. RESULTS: For 2000, across six sites, a total of 1,252 children aged 8 years were identified as having an ASD. The overall prevalence of ASDs per 1,000 children aged 8 years ranged from 4.5 in West Virginia to 9.9 in New Jersey. With the exception of one surveillance site (Georgia), no statistically significant (p<0.05) differences were identified in the rate of ASDs between non-Hispanic black and non-Hispanic white children. The ratio of male-to-female prevalence varied (range: 2.8:1.0-5.5:1.0). The majority of children with ASDs received special education services and had a documented history of concerns regarding their development before age 3 years. The prevalence of children with a previously documented ASD classification varied across sites, but the median age of earliest documented ASD diagnosis was similar across sites (age 52-56 months). For three sites with sufficient data on intelligence quotient (IQ), cognitive impairment (i.e., IQ of lemongrass > clove, palmarose, peppermint, lavender > geranium Bourbon, tea tree > thyme geraniol oils. MFCs were further reduced to 1/2 - 1/8 by the addition of 10% sodium chloride. The salt effect was explained, at least partly, by an increase in mycelial adsorption of antifungal constituents in the presence of sodium chloride. Considerable hyphal damage was done at 27 degrees C by the essential oils, but no further alteration in morphology of the hyphae treated at 42 degrees C with or without oil was observed by SEM. The inhibitory effect of heat and oils was also observed against mycelia of T. rubrum and conidia of T. mentagrophytes. Thermotherapy combined with essential oils and salt would be promising to treat tinea pedis in a foot bath. PMID- 17287721 TI - Molecular phylogenetics of multiple genes on Aspergillus section Fumigati isolated from clinical specimens in Japan. AB - A phylogenetic study based on sequence analysis of the beta-tubulin, hydrophobin and calmodulin genes was performed in 19 strains of Aspergillus fumigatus and related species isolated from clinical specimens in Japan. Correlations between detailed morphology and phylogeny were examined. Species in the section Fumigati were divided into five clades: clade I, typical strains of A. fumigatus; clade II, species including A. lentulus and A. fumisynnematus; clade III, species including A. fumigatiaffinis and A. novofumigatus, clade IV, atypical strains of A. fumigatus including A. viridinutans; and clade V, species including A. brevipes, A. duricaulis and A. unilateralis. Most of the examined strains from clinical specimens in Japan clustered together in clade I and exhibit globose conidia with lobate-reticulate ornamentation. Other strains from clinical specimens were divided into two clades (clades II and IV). The strains in clades II and the six strains in clade IV exhibit conidia with microtuberculate ornamentation, while A. viridinutans-complex in clades IV and the strains in clade V have conidia with lobate-reticulate ornamentation. The six strains are clearly distinguished from A. viridinutans-complex and are considered to be related to Neosartorya udagawae. The maximal growth temperatures of clades I, II, IV and V were above 50 degrees C, 45 degrees C, 42 degrees C and 42 degrees C, respectively. These data are useful for classification of species within the Aspergillus section Fumigati. PMID- 17287722 TI - In-vitro antifungal activities of sulfa drugs against clinical isolates of Aspergillus and Cryptococcus species. AB - In vitro susceptibilities of ten clinical isolates, including five strains of Cryptococcus neoformans var. grubii and five strains of Aspergillus fumigatus, were determined against nine sulfa drugs using a microdilution method. Among the five tested media, minimum inhibitory concentration (MIC) values were observed only in YNB medium: no detectable level MIC value of less than 125 microg/ml was observed in the four remaining media against Cryptococcus species. Of the nine sulfa drugs, of which sulfaphenazole showed the highest antifungal activity, the MIC values for A. fumigatus and C. neoformans var. grubii were, respectively, 64 microg/ml and 4-8 microg/ml, suggesting high susceptibility of C. neoformans to sulfa drugs. PMID- 17287723 TI - A recurrent mutation in PALB2 in Finnish cancer families. AB - BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer. Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified. The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity. Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development. PMID- 17287724 TI - Continental ice in Greenland during the Eocene and Oligocene. AB - The Eocene and Oligocene epochs (approximately 55 to 23 million years ago) comprise a critical phase in Earth history. An array of geological records supported by climate modelling indicates a profound shift in global climate during this interval, from a state that was largely free of polar ice caps to one in which ice sheets on Antarctica approached their modern size. However, the early glaciation history of the Northern Hemisphere is a subject of controversy. Here we report stratigraphically extensive ice-rafted debris, including macroscopic dropstones, in late Eocene to early Oligocene sediments from the Norwegian-Greenland Sea that were deposited between about 38 and 30 million years ago. Our data indicate sediment rafting by glacial ice, rather than sea ice, and point to East Greenland as the likely source. Records of this type from one site alone cannot be used to determine the extent of ice involved. However, our data suggest the existence of (at least) isolated glaciers on Greenland about 20 million years earlier than previously documented, at a time when temperatures and atmospheric carbon dioxide concentrations were substantially higher. PMID- 17287726 TI - Female fur seals show active choice for males that are heterozygous and unrelated. AB - Much debate surrounds the exact rules that influence mating behaviour, and in particular the selective forces that explain the evolution of female preferences. A key example is the lek paradox, in which female choice is expected rapidly to become ineffective owing to loss of additive genetic variability for the preferred traits. Here we exploit a remarkable system in which female fur seals exert choice by moving across a crowded breeding colony to visit largely static males. We show that females move further to maximize the balance between male high multilocus heterozygosity and low relatedness. Such a system shows that female choice can be important even in a strongly polygynous species, and at the same time may help to resolve the lek paradox because heterozygosity has low heritability and inbreeding avoidance means there is no single 'best' male for all females. PMID- 17287727 TI - Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. AB - At least five arenaviruses cause viral haemorrhagic fevers in humans. Lassa virus, an Old World arenavirus, uses the cellular receptor alpha-dystroglycan to infect cells. Machupo, Guanarito, Junin and Sabia viruses are New World haemorrhagic fever viruses that do not use alpha-dystroglycan. Here we show a specific, high-affinity association between transferrin receptor 1 (TfR1) and the entry glycoprotein (GP) of Machupo virus. Expression of human TfR1, but not human transferrin receptor 2, in hamster cell lines markedly enhanced the infection of viruses pseudotyped with the GP of Machupo, Guanarito and Junin viruses, but not with those of Lassa or lymphocytic choriomeningitis viruses. An anti-TfR1 antibody efficiently inhibited the replication of Machupo, Guanarito, Junin and Sabia viruses, but not that of Lassa virus. Iron depletion of culture medium enhanced, and iron supplementation decreased, the efficiency of infection by Junin and Machupo but not Lassa pseudoviruses. These data indicate that TfR1 is a cellular receptor for New World haemorrhagic fever arenaviruses. PMID- 17287728 TI - TRAPPI tethers COPII vesicles by binding the coat subunit Sec23. AB - The budding of endoplasmic reticulum (ER)-derived vesicles is dependent on the COPII coat complex. Coat assembly is initiated when Sar1-GTP recruits the cargo adaptor complex, Sec23/Sec24, by binding to its GTPase-activating protein (GAP) Sec23 (ref. 2). This leads to the capture of transmembrane cargo by Sec24 (refs 3, 4) before the coat is polymerized by the Sec13/Sec31 complex. The initial interaction of a vesicle with its target membrane is mediated by tethers. We report here that in yeast and mammalian cells the tethering complex TRAPPI (ref. 7) binds to the coat subunit Sec23. This event requires the Bet3 subunit. In vitro studies demonstrate that the interaction between Sec23 and Bet3 targets TRAPPI to COPII vesicles to mediate vesicle tethering. We propose that the binding of TRAPPI to Sec23 marks a coated vesicle for fusion with another COPII vesicle or the Golgi apparatus. An implication of these findings is that the intracellular destination of a transport vesicle may be determined in part by its coat and its associated cargo. PMID- 17287725 TI - An African origin for the intimate association between humans and Helicobacter pylori. AB - Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, although H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation, the age of an association between these bacteria with humans remains highly controversial. Here we show, using sequences from a large data set of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from east Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from east Africa around 58,000 yr ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli Sforza and colleagues. Taken together, our results establish that anatomically modern humans were already infected by H. pylori before their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since. PMID- 17287730 TI - Hearts and minds. AB - The nonprofit Pew Initiative on Food and Biotechnology is closing, but the need for an independent and neutral body to facilitate dialog on US biotech policy has never been greater. PMID- 17287729 TI - CD38 is critical for social behaviour by regulating oxytocin secretion. AB - CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders. PMID- 17287731 TI - Life support for life science innovation? AB - think tank and an investment bank have proposed solutions to address the lack of funding to carry biotech companies through the early stages of clinical development. PMID- 17287732 TI - Commercial interest grows in glycan analysis. PMID- 17287733 TI - Chinese biotech hamstrung by production issues. PMID- 17287734 TI - Next-generation sequencing outpaces expectations. PMID- 17287735 TI - Democrats prioritize pricing, generics and drug safety. PMID- 17287737 TI - Profile: Jean-Paul Clozel. PMID- 17287738 TI - 2006: a stellar year for financing. PMID- 17287739 TI - Reality check for device-drug convergence. PMID- 17287741 TI - Blame factory farming, not organic food. PMID- 17287742 TI - The fit between organic and pharma crops in North Carolina. PMID- 17287744 TI - Genetically modified lignin below ground. PMID- 17287745 TI - Model for tuning GMO detection in seed and grain. PMID- 17287746 TI - ATP and FRET--a cautionary note. PMID- 17287747 TI - Bringing antivenoms to Sub-Saharan Africa. AB - To reduce unacceptably high death rates from snakebite envenomation, sub-Saharan Africa must adopt not only a new generation of multivalent biotech antivenoms, but also an infrastructure to deliver them. PMID- 17287749 TI - Turning biodefense dollars into products. AB - Five years after the US anthrax attacks, and more than two years after BioShield legislation was ratified, a survey reveals that biodefense funding has thus far produced only a handful of products for clinical development. PMID- 17287751 TI - Recent patent applications in biomedical devices. PMID- 17287750 TI - DNA patenting: the end of an era? AB - Debates on patenting DNA must evolve to reflect the global decline in filings and regional disparities in patenting activity. PMID- 17287752 TI - The genome of an industrial workhorse. PMID- 17287753 TI - Lentiviruses to the placental rescue. PMID- 17287754 TI - Calreticulin exposure increases cancer immunogenicity. PMID- 17287755 TI - Targeting brain-tumor stem cells. PMID- 17287757 TI - Relating protein pharmacology by ligand chemistry. AB - The identification of protein function based on biological information is an area of intense research. Here we consider a complementary technique that quantitatively groups and relates proteins based on the chemical similarity of their ligands. We began with 65,000 ligands annotated into sets for hundreds of drug targets. The similarity score between each set was calculated using ligand topology. A statistical model was developed to rank the significance of the resulting similarity scores, which are expressed as a minimum spanning tree to map the sets together. Although these maps are connected solely by chemical similarity, biologically sensible clusters nevertheless emerged. Links among unexpected targets also emerged, among them that methadone, emetine and loperamide (Imodium) may antagonize muscarinic M3, alpha2 adrenergic and neurokinin NK2 receptors, respectively. These predictions were subsequently confirmed experimentally. Relating receptors by ligand chemistry organizes biology to reveal unexpected relationships that may be assayed using the ligands themselves. PMID- 17287758 TI - Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. AB - The application of human embryonic stem cells (HESCs) to provide differentiated cells for regenerative medicine will require the continuous maintenance of the undifferentiated stem cells for long periods in culture. However, chromosomal stability during extended passaging cannot be guaranteed, as recent cytogenetic studies of HESCs have shown karyotypic aberrations. The observed karyotypic aberrations probably reflect the progressive adaptation of self-renewing cells to their culture conditions. Genetic change that increases the capacity of cells to proliferate has obvious parallels with malignant transformation, and we propose that the changes observed in HESCs in culture reflect tumorigenic events that occur in vivo, particularly in testicular germ cell tumors. Further supporting a link between culture adaptation and malignancy, we have observed the formation of a chromosomal homogeneous staining region in one HESC line, a genetic feature almost a hallmark of cancer cells. Identifying the genes critical for culture adaptation may thus reveal key players for both stem cell maintenance in vitro and germ cell tumorigenesis in vivo. PMID- 17287762 TI - Strength in diversity: a cross-disciplinary approach to graduate training in chemical biology. AB - Chemical biology graduate programs that are jointly organized by chemistry and life science departments can offer a stimulating 'bicultural' training environment for students from diverse backgrounds. However, communication, flexibility and responsiveness are crucial for effectively structuring such programs. PMID- 17287765 TI - Veterinary epidemiology: vaccination strategies for foot-and-mouth disease. AB - When foot-and-mouth disease struck the United Kingdom in 2001, the traditional 'stamping out' policy of 1967-68 was supplemented by the pre-emptive culling of animals in premises contiguous to infected premises. A model proposed by Tildesley et al. indicates that the introduction of vaccination should at least halve the number of premises that would need to be subjected to culling in the event of another outbreak. We contest, however, that the overlapping confidence intervals of the outputs of their model, and the inconsistency of their results compared with those from previous models, call into question the model's value as a decision tool, while adding little to the recognized tenet of ring vaccination. PMID- 17287769 TI - Light at the end of the tunnel. PMID- 17287770 TI - Welcome home. PMID- 17287771 TI - Steady progress. PMID- 17287773 TI - Bush and Congress set debate on priorities. PMID- 17287774 TI - Dig links Stonehenge to circle of life. PMID- 17287776 TI - Virus paper reignites prion spat. PMID- 17287777 TI - Africa pursues goal of scientific unity. PMID- 17287779 TI - Special report: from words to action. PMID- 17287780 TI - Climate change 2007: what they're saying. PMID- 17287781 TI - Climate change 2007: what we don't know about climate change. PMID- 17287782 TI - Climate change 2007: data keep flooding in. PMID- 17287784 TI - Climate change 2007: climate sceptics switch focus to economics. PMID- 17287783 TI - Climate change 2007: what price a cooler future? PMID- 17287785 TI - Carbon copies. PMID- 17287788 TI - Energy efficiency: super savers: meters to manage the future. PMID- 17287789 TI - Energy efficiency: super savers: experimenting with efficiency. PMID- 17287791 TI - Colour-blindness: how to alienate a grant reviewer. PMID- 17287792 TI - Getting that first scent of life while we're in the womb. PMID- 17287793 TI - How important is immune memory to invertebrates? PMID- 17287794 TI - Is the global carbon market working? PMID- 17287795 TI - Climate change 2007: lifting the taboo on adaptation. PMID- 17287800 TI - A clash of two cultures. PMID- 17287801 TI - Quantum physics: indistinguishable from afar. PMID- 17287802 TI - Palaeoclimate: when the world turned cold. PMID- 17287803 TI - Evolutionary biology: out of thin air. PMID- 17287804 TI - Coherent control of optical information with matter wave dynamics. AB - In recent years, significant progress has been achieved in manipulating matter with light, and light with matter. Resonant laser fields interacting with cold, dense atom clouds provide a particularly rich system. Such light fields interact strongly with the internal electrons of the atoms, and couple directly to external atomic motion through recoil momenta imparted when photons are absorbed and emitted. Ultraslow light propagation in Bose-Einstein condensates represents an extreme example of resonant light manipulation using cold atoms. Here we demonstrate that a slow light pulse can be stopped and stored in one Bose Einstein condensate and subsequently revived from a totally different condensate, 160 mum away; information is transferred through conversion of the optical pulse into a travelling matter wave. In the presence of an optical coupling field, a probe laser pulse is first injected into one of the condensates where it is spatially compressed to a length much shorter than the coherent extent of the condensate. The coupling field is then turned off, leaving the atoms in the first condensate in quantum superposition states that comprise a stationary component and a recoiling component in a different internal state. The amplitude and phase of the spatially localized light pulse are imprinted on the recoiling part of the wavefunction, which moves towards the second condensate. When this 'messenger' atom pulse is embedded in the second condensate, the system is re-illuminated with the coupling laser. The probe light is driven back on and the messenger pulse is coherently added to the matter field of the second condensate by way of slow-light-mediated atomic matter-wave amplification. The revived light pulse records the relative amplitude and phase between the recoiling atomic imprint and the revival condensate. Our results provide a dramatic demonstration of coherent optical information processing with matter wave dynamics. Such quantum control may find application in quantum information processing and wavefunction sculpting. PMID- 17287805 TI - Molecular fingerprinting with the resolved modes of a femtosecond laser frequency comb. AB - The control of the broadband frequency comb emitted from a mode-locked femtosecond laser has permitted a wide range of scientific and technological advances--ranging from the counting of optical cycles for next-generation atomic clocks to measurements of phase-sensitive high-field processes. A unique advantage of the stabilized frequency comb is that it provides, in a single laser beam, about a million optical modes with very narrow linewidths and absolute frequency positions known to better than one part in 10(15) (ref. 5). One important application of this vast array of highly coherent optical fields is precision spectroscopy, in which a large number of modes can be used to map internal atomic energy structure and dynamics. However, an efficient means of simultaneously identifying, addressing and measuring the amplitude or relative phase of individual modes has not existed. Here we use a high-resolution disperser to separate the individual modes of a stabilized frequency comb into a two-dimensional array in the image plane of the spectrometer. We illustrate the power of this technique for high-resolution spectral fingerprinting of molecular iodine vapour, acquiring in a few milliseconds absorption images covering over 6 THz of bandwidth with high frequency resolution. Our technique for direct and parallel accessing of stabilized frequency comb modes could find application in high-bandwidth spread-spectrum communications with increased security, high resolution coherent quantum control, and arbitrary optical waveform synthesis with control at the optical radian level. PMID- 17287806 TI - Patterning of sodium ions and the control of electrons in sodium cobaltate. AB - Sodium cobaltate (Na(x)CoO2) has emerged as a material of exceptional scientific interest due to the potential for thermoelectric applications, and because the strong interplay between the magnetic and superconducting properties has led to close comparisons with the physics of the superconducting copper oxides. The density x of the sodium in the intercalation layers can be altered electrochemically, directly changing the number of conduction electrons on the triangular Co layers. Recent electron diffraction measurements reveal a kaleidoscope of Na+ ion patterns as a function of concentration. Here we use single-crystal neutron diffraction supported by numerical simulations to determine the long-range three-dimensional superstructures of these ions. We show that the sodium ordering and its associated distortion field are governed by pure electrostatics, and that the organizational principle is the stabilization of charge droplets that order long range at some simple fractional fillings. Our results provide a good starting point to understand the electronic properties in terms of a Hubbard hamiltonian that takes into account the electrostatic potential from the Na superstructures. The resulting depth of potential wells in the Co layer is greater than the single-particle hopping kinetic energy and as a consequence, holes preferentially occupy the lowest potential regions. Thus we conclude that the Na+ ion patterning has a decisive role in the transport and magnetic properties. PMID- 17287807 TI - Tibetan plateau aridification linked to global cooling at the Eocene-Oligocene transition. AB - Continental aridification and the intensification of the monsoons in Asia are generally attributed to uplift of the Tibetan plateau and to the land-sea redistributions associated with the continental collision of India and Asia, whereas some studies suggest that past changes in Asian environments are mainly governed by global climate. The most dramatic climate event since the onset of the collision of India and Asia is the Eocene-Oligocene transition, an abrupt cooling step associated with the onset of glaciation in Antarctica 34 million years ago. However, the influence of this global event on Asian environments is poorly understood. Here we use magnetostratigraphy and cyclostratigraphy to show that aridification, which is indicated by the disappearance of playa lake deposits in the northeastern Tibetan plateau, occurred precisely at the time of the Eocene-Oligocene transition. Our findings suggest that this global transition is linked to significant aridification and cooling in continental Asia recorded by palaeontological and palaeoenvironmental changes, and thus support the idea that global cooling is associated with the Eocene-Oligocene transition. We show that, with sufficient age control on the sedimentary records, global climate can be distinguished from tectonism and recognized as a major contributor to continental Asian environments. PMID- 17287808 TI - Large temperature drop across the Eocene-Oligocene transition in central North America. AB - The Eocene-Oligocene transition towards a cool climate (approximately 33.5 million years ago) was one of the most pronounced climate events during the Cenozoic era. The marine record of this transition has been extensively studied. However, significantly less research has focused on continental climate change at the time, yielding partly inconsistent results on the magnitude and timing of the changes. Here we use a combination of in vivo stable isotope compositions of fossil tooth enamel with diagenetic stable isotope compositions of fossil bone to derive a high-resolution (about 40,000 years) continental temperature record for the Eocene-Oligocene transition. We find a large drop in mean annual temperature of 8.2 +/- 3.1 degrees C over about 400,000 years, the possibility of a small increase in temperature seasonality, and no resolvable change in aridity across the transition. The large change in mean annual temperature, exceeding changes in sea surface temperatures at comparable latitudes and possibly delayed in time with respect to marine changes by up to 400,000 years, explains the faunal turnover for gastropods, amphibians and reptiles, whereas most mammals in the region were unaffected. Our results are in agreement with modelling studies that attribute the climate cooling at the Eocene-Oligocene transition to a significant drop in atmospheric carbon dioxide concentrations. PMID- 17287809 TI - Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models. AB - The striatum is a major forebrain nucleus that integrates cortical and thalamic afferents and forms the input nucleus of the basal ganglia. Striatal projection neurons target the substantia nigra pars reticulata (direct pathway) or the lateral globus pallidus (indirect pathway). Imbalances between neural activity in these two pathways have been proposed to underlie the profound motor deficits observed in Parkinson's disease and Huntington's disease. However, little is known about differences in cellular and synaptic properties in these circuits. Indeed, current hypotheses suggest that these cells express similar forms of synaptic plasticity. Here we show that excitatory synapses onto indirect-pathway medium spiny neurons (MSNs) exhibit higher release probability and larger N methyl-d-aspartate receptor currents than direct-pathway synapses. Moreover, indirect-pathway MSNs selectively express endocannabinoid-mediated long-term depression (eCB-LTD), which requires dopamine D2 receptor activation. In models of Parkinson's disease, indirect-pathway eCB-LTD is absent but is rescued by a D2 receptor agonist or inhibitors of endocannabinoid degradation. Administration of these drugs together in vivo reduces parkinsonian motor deficits, suggesting that endocannabinoid-mediated depression of indirect-pathway synapses has a critical role in the control of movement. These findings have implications for understanding the normal functions of the basal ganglia, and also suggest approaches for the development of therapeutic drugs for the treatment of striatal based brain disorders. PMID- 17287810 TI - Direct control of shoot meristem activity by a cytokinin-activating enzyme. AB - The growth of plants depends on continuous function of the meristems. Shoot meristems are responsible for all the post-embryonic aerial organs, such as leaves, stems and flowers. It has been assumed that the phytohormone cytokinin has a positive role in shoot meristem function. A severe reduction in the size of meristems in a mutant that is defective in all of its cytokinin receptors has provided compelling evidence that cytokinin is required for meristem activity. Here, we report a novel regulation of meristem activity, which is executed by the meristem-specific activation of cytokinins. The LONELY GUY (LOG) gene of rice is required to maintain meristem activity and its loss of function causes premature termination of the shoot meristem. LOG encodes a novel cytokinin-activating enzyme that works in the final step of bioactive cytokinin synthesis. Revising the long-held idea of multistep reactions, LOG directly converts inactive cytokinin nucleotides to the free-base forms, which are biologically active, by its cytokinin-specific phosphoribohydrolase activity. LOG messenger RNA is specifically localized in shoot meristem tips, indicating the activation of cytokinins in a specific developmental domain. We propose the fine-tuning of concentrations and the spatial distribution of bioactive cytokinins by a cytokinin-activating enzyme as a mechanism that regulates meristem activity. PMID- 17287811 TI - Sheets, ribbons and tubules - how organelles get their shape. AB - Most membrane-bound organelles have elaborate, dynamic shapes and often include regions with distinct morphologies. These complex structures are relatively conserved throughout evolution, which indicates that they are important for optimal organelle function. Various mechanisms of determining organelle shape have been proposed - proteins that stabilize highly curved membranes, the tethering of organelles to other cellular components and the regulation of membrane fission and fusion might all contribute. PMID- 17287812 TI - Molecular mechanism of the nuclear protein import cycle. AB - The nuclear import of proteins through nuclear pore complexes (NPCs) illustrates how a complex biological function can be generated by a spatially and temporally organized cycle of interactions between cargoes, carriers and the Ran GTPase. Recent work has given considerable insight into this process, especially about how interactions are coordinated and the basis for the molecular recognition that underlies the process. Although considerable progress has been made in identifying and characterizing the molecular interactions in the soluble phase that drive the nuclear protein import cycle, understanding the precise mechanism of translocation through NPCs remains a major challenge. PMID- 17287814 TI - Intelligently designed clinical studies. PMID- 17287815 TI - An unusual renal colic: a tribute to Joseph Hyrtl (1810-1894) and Max Brodel (1870-1941). PMID- 17287816 TI - Vascular calcification: not so crystal clear. AB - Patients with renal failure are predisposed to calcification of the medial layer of arteries. This calcification is far more complex than simple precipitation of calcium and phosphate and involves multiple forms of calcium phosphate. Like bone, calcification in the vessels also involves biologic events. The two are necessarily linked and unraveling the pathophysiology will require an understanding of both. PMID- 17287817 TI - The not-so-minimal lesions of the idiopathic nephrotic syndrome of childhood. AB - Dijkman et al. describe a unique form of glomerular involution in children with idiopathic nephrotic syndrome (INS). These lesions are small and sclerotic but retain their podocyte and parietal epithelial cell constituents. Multicenter studies are needed to address the clinical implications of the changing histological pattern of INS in children. PMID- 17287818 TI - Vasopressin: a look at dialysis hypertension and autonomic dysfunction. AB - Dialysis hypertension is a complex disorder in which ambient vascular resistance is too high for the blood volume. van der Zee et al. remind us that this is contingent upon the endothelium itself, and that endothelial dysfunction is integral to uremia. Thus, while vasopressin may not abolish dialysis hypotension, its effects highlight the influence of uremia on the autocrine and neuroendocrine control of cardiovascular physiology. PMID- 17287821 TI - Cellular mechanisms underlying the anxiolytic effect of low doses of peripheral Delta9-tetrahydrocannabinol in rats. AB - We investigated the effect of low doses of intraperitoneal Delta(9) tetrahydrocannabinol (THC) on anxiety behavior in rats using the elevated plus maze (EPM). An anxiolytic effect was obtained in a range of doses between 0.075 and 1.5 mg/kg, the 0.75 dose being the most effective. Pretreatment with the CB1 receptor antagonist AM251 fully reversed THC's effect, suggesting CB1 receptors were involved. In order to elucidate the neuroanatomical substrates underlying the effect of the maximal effective dose of THC, we investigated cFos expression in anxiety-related brain regions (prefrontal cortex, nucleus accumbens, amygdala, and hippocampus) of rats exposed to the EPM. THC significantly lowered the amount of cFos in prefrontal cortex and amygdala without affecting the other cerebral areas. As there is increasing evidence that CREB function regulates anxiety-like behavior in rats, the second biochemical parameter we measured was phosphorylated CREB in the same brain areas. Rats treated with THC showed a significant increase in CREB activation in the prefrontal cortex and hippocampus. In the prefrontal cortex this increased activation was linked to an increase in ERK activation, whereas in the hippocampus there was a drop in the activity of CAMKII, a kinase with inhibitory effect on CREB activation. All these effects were reversed by AM251 pretreatment, suggesting that stimulation of CB1 receptors is fundamental for triggering the biochemical events. Our results suggest that the stimulation of these receptors in the prefrontal cortex, amygdala, and hippocampus with the subsequent activation of different signaling pathways is the first event underlying the effects of cannabinoids on anxious states. PMID- 17287822 TI - Mapping the effects of three dopamine agonists with different dyskinetogenic potential and receptor selectivity using pharmacological functional magnetic resonance imaging. AB - The mechanisms underlying dopamine agonist-induced dyskinesia in Parkinson's disease remain poorly understood. Similar to patients, rats with severe nigrostriatal degeneration induced by 6-hydroxydopamine are more likely to show dyskinesia during chronic treatment with unselective dopamine receptor agonists than with D2 agonists, suggesting that D1 receptor stimulation alone or in conjunction with D2 receptor stimulation increases the chances of experiencing dyskinesia. As a first step towards disclosing drug-induced brain activation in dyskinesia, we examined the effects of dopamine agonists on behavior and blood oxygenation level-dependent (BOLD) signal in the striatum and motor cortex of rats with unilateral nigrostriatal lesions. Rats were rendered dyskinetic before pharmacologic functional magnetic resonance imaging by means of a repeated treatment regime with dopamine agonists. The unselective agonist apomorphine and the selective D1/D5 agonist SKF-81297 induced strong forelimb dyskinesia (FD) and axial dystonia and increased BOLD signal in the denervated striatum. Besides, SKF 81297 produced a significant but smaller BOLD increase in the intact striatum and a symmetric bilateral increase in the motor cortex. The D2 family agonist quinpirole, which induced mild dyskinesia on chronic treatment, did not produce BOLD changes in the striatum or motor cortex. Further evidence to support an association between BOLD changes and dyskinesia comes from a direct correlation between scores of FD and magnitude of drug-induced BOLD increases in the denervated striatum and motor cortex. Our results suggest that striatal and cortical activation induced by stimulation of D1/D5 receptors has a primary role in the induction of peak dose dyskinesia in parkinsonism. PMID- 17287823 TI - High-affinity CRF1 receptor antagonist NBI-34041: preclinical and clinical data suggest safety and efficacy in attenuating elevated stress response. AB - There is an extensive evidence that corticotropin releasing factor (CRF) is hypersecreted in depression and anxiety, and blockade of CRF could have therapeutic benefit. We report preclinical data and the results of a clinical Phase I study with the novel nonpeptide CRF(1) antagonist NBI-34041/SB723620. Preclinical data conducted with different cell lines expressing human CRF receptors and in Wistar and Sprague-Dawley rats indicate that NBI-34041 is effective in reducing endocrine responses to pharmacological and behavioral challenge mediated by CRF(1) receptors. These specific properties and its well documented safety profile enabled a clinical Phase I study with 24 healthy male subjects receiving NBI-34041 (10, 50, or 100 mg) or placebo for 14 days. Regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis was evaluated by intravenous stimulation with 100 microg of human CRF. Psychosocial stress response was investigated with the Trier Social Stress Test (TSST). Treatment with NBI-34041 did not impair diurnal adrenocorticotropic hormone (ACTH) and cortisol secretion or CRF evoked ACTH and cortisol responses but attenuated the neuroendocrine response to psychosocial stress. These results suggest that NBI 34041 is safe and does not impair basal regulation of the HPA system but improves resistance against psychosocial stress. NBI-34041 demonstrates that inhibition of the CRF system is a promising target for drug development against depression and anxiety disorders. PMID- 17287824 TI - Acetaldehyde, a major constituent of tobacco smoke, enhances behavioral, endocrine, and neuronal responses to nicotine in adolescent and adult rats. AB - We have previously shown that acetaldehyde, a constituent of tobacco smoke, increases nicotine self-administration in adolescent, but not adult, rats. The aim of this study was to determine whether acetaldehyde influences other behavioral, endocrine, or neuronal responses to nicotine at either age. Juvenile (postnatal day (P) 27) and adult (P90) male Sprague-Dawley rats were treated with saline, acetaldehyde (16 microg/kg/injection x 2, i.v.), nicotine (30 microg/kg/injection x 2, i.v.) or a combination of acetaldehyde and nicotine. Locomotion and center time were evaluated for 30 min in a novel open field, before measurement of plasma corticosterone levels and brain c-fos mRNA. Nicotine increased locomotor activity in juveniles but decreased it in adults; in contrast, center time was increased at both ages. Acetaldehyde potentiated nicotine's locomotor effects, but not center time. Nicotine induced c-fos expression in the bed nucleus of the stria terminalis, the central nucleus of the amygdala (CeA), nucleus accumbens, and the superior colliculus (SC) at both ages, whereas it activated the hypothalamic paraventricular nucleus (PVN) and consequent corticosterone secretion only in adults. Acetaldehyde potentiated nicotine-induced c-fos in CeA and SC, and activation of PVN c-fos expression/plasma corticosterone release; however, this drug interaction was only observed in behaviorally tested animals, not those that were minimally stressed. Thus, acetaldehyde may modulate the interaction of nicotine and stress. Although pharmacokinetic studies showed that acetaldehyde did not change nicotine levels in either brain or serum, nicotine penetration into the brain was slower in juveniles as compared to adults. PMID- 17287825 TI - Defining 'response' in antipsychotic drug trials: recommendations for the use of scale-derived cutoffs. AB - Scale-derived cutoff points are frequently used to define 'response' in antipsychotic drug trials. This procedure is useful, because responder rates can be understood more intuitively than a difference in means of rating scales. As various definitions of response have been used, we examined original participant data to assess whether the choice of the Brief Psychiatric Rating Scale-based response cutoff had an impact on the results of seven (n=1870) antipsychotic drug trials in schizophrenia. We also analyzed whether the chronicity of the illness has an impact on the question of which cutoff is most sensitive in detecting differences between drugs. The results in terms of p-values and response rate differences varied substantially in dependence on the cutoff chosen. The use of response rate ratios attenuated the variability. In contrast to a widely held belief, low response cutoffs were not more sensitive in detecting differences between drugs than higher cutoffs. In more chronic, less responsive participants, there was a trend for higher cutoffs to be less sensitive in detecting differences between drugs than lower ones. The results of clinical trials depend considerably on the response cutoff chosen. Therefore, the cutoff should never be chosen post hoc, a large range of cutoffs should be presented and the a priori choice of the primary cutoff should be based on clinical relevance. The use of ratios rather than differences attenuates the variability. Cutoffs need to be calculated on the basis of 0-6 rather than on 1-7 scoring systems. We suggest a table presenting responder rates in 25 percent steps covering the whole range up to 100% reduction from baseline, which could be displayed together with recently presented criteria for remission. PMID- 17287826 TI - Inhibiting transient protein-protein interactions: lessons from the Cdc25 protein tyrosine phosphatases. AB - Transient protein-protein interactions have key regulatory functions in many of the cellular processes that are implicated in cancerous growth, particularly the cell cycle. Targeting these transient interactions as therapeutic targets for anticancer drug development seems like a good idea, but it is not a trivial task. This Review discusses the issues and difficulties that are encountered when considering these transient interactions as drug targets, using the example of the cell division cycle 25 (Cdc25) phosphatases and their cyclin-dependent kinase (CDK)-cyclin protein substrates. PMID- 17287827 TI - Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis. AB - The pathogenesis of viral myocarditis is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a model of infection with coxsackievirus B3 (CVB3) to characterize the contribution of host genetics to viral myocarditis in mice of different genetic backgrounds but with a common H2 haplotype: A/J and B10.A-H2(a). Here we have used Evans blue dye as a quantitative biomarker for susceptibility to CVB3 induced myocarditis in addition to histopathological semiquantitative measures. We have found evidence of linkage between susceptibility to viral myocarditis and three loci. A locus on chromosome 1 centered on D1Mit200 was linked to sarcolemmal disruption in males (P=0.00005), a second locus on chromosome 4 centered on D4Mit81 was also linked to sarcolemmal disruption in males (P=0.0022). A third locus on distal chromosome 3 centered on D3Mit19 was linked to myocardial infiltration, with a logarithm of odds (LOD) score of 4.7 (P=0.0045), as well as sarcolemmal disruption in females (P=0.0015). These results provide strong evidence for the presence of loci contributing to the susceptibility of mice to viral myocarditis. PMID- 17287828 TI - Nuclear reprogramming: the strategy used in normal development is also used in somatic cell nuclear transfer and parthenogenesis. AB - Somatic cell nuclear transfer (SCNT) and parthenogenesis are alternative forms of reproduction and development, building new life cycles on differentiated somatic cell nuclei and duplicated maternal chromatin, respectively. In the preceding paper (Sun F, et al., Cell Res 2007; 17:117-134.), we showed that an "erase-and rebuild" strategy is used in normal development to transform the maternal gene expression profile to a zygotic one. Here, we investigate if the same strategy also applies to SCNT and parthenogenesis. The relationship between chromatin and chromatin factors (CFs) during SCNT and parthenogenesis was examined using immunochemical and GFP-fusion protein assays. Results from these studies indicated that soon after nuclear transfer, a majority of CFs dissociated from somatic nuclei and were redistributed to the cytoplasm of the egg. The erasure process in oogenesis is recaptured during the initial phase in SCNT. Most CFs entered pseudo-pronuclei shortly after their formation. In parthenogenesis, all parthenogenotes underwent normal oogenesis, and thus had removed most CFs from chromosomes before the initiation of development. The CFs were subsequently re associated with female pronuclei in time and sequence similar to that in fertilized embryos. Based on these data, we conclude that the "erase-and-rebuild" process observed in normal development also occurs in SCNT and in parthenogenesis, albeit in altered fashions. The process is responsible for transcription reprogramming in these procedures. The "erase" process in SCNT is compressed and the efficiency is compromised, which likely contribute to the developmental defects often observed in nuclear transfer (nt) embryos. Furthermore, results from this study indicated that the cytoplasm of an egg contains most, if not all, essential components for assembling the zygotic program and can assemble them onto appropriate diploid chromatin of distinct origins. PMID- 17287829 TI - Nuclear reprogramming: the zygotic transcription program is established through an "erase-and-rebuild" strategy. AB - Oocytes display a maternal-specific gene expression profile, which is switched to a zygotic profile when a haploid set of chromatin is passed on to the fertilized egg that develops into an embryo. The mechanism underlying this transcription reprogramming is currently unknown. Here we demonstrate that by the time when transcription is shut down in germinal vesicle oocytes, a range of general transcription factors and transcriptional regulators are dissociated from the chromatin. The global dissociation of chromatin factors (CFs) disrupts physical contacts between the chromatin and CFs and leads to erasure of the maternal transcription program at the functional level. Critical transcription factors and regulators remain separated from chromatin for a prolonged period, and become re associated with chromatin shortly after pronuclear formation. This is followed temporally by the re-establishment of nuclear functions such as DNA replication and transcription. We propose that the maternal transcription program is erased during oogenesis to generate a relatively naive chromatin and the zygotic transcription program is rebuilt de novo after fertilization. This process is termed as the "erase-and-rebuild" process, which is used to reset the transcription program, and most likely other nuclear processes as well, from a maternal one to that of the embryo. We further show in the accompanying paper (Gao T, et al., Cell Res 2007; 17: 135-150.) that the same strategy is also employed to reprogram transcriptional profiles in somatic cell nuclear transfer and parthenogenesis, suggesting that this model is universally applicable to all forms of transcriptional reprogramming during early embryogenesis. Displacement of CFs from chromatin also offers an explanation for the phenomenon of transcription silence during the maternal to zygotic transition. PMID- 17287830 TI - Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair. AB - The partitioning-defective 3 (Par3), a key component in the conserved Par3/Par6/aPKC complex, plays fundamental roles in cell polarity. Herein we report the identification of Ku70 and Ku80 as novel Par3-interacting proteins through an in vitro binding assay followed by liquid chromatography-tandem mass spectrometry. Ku70/Ku80 proteins are two key regulatory subunits of the DNA dependent protein kinase (DNA-PK), which plays an essential role in repairing double-strand DNA breaks (DSBs). We determined that the nuclear association of Par3 with Ku70/Ku80 was enhanced by gamma-irradiation (IR), a potent DSB inducer. Furthermore, DNA-PKcs, the catalytic subunit of DNA-PK, interacted with the Par3/Ku70/Ku80 complex in response to IR. Par3 over-expression or knockdown was capable of up- or downregulating DNA-PK activity, respectively. Moreover, the Par3 knockdown cells were found to be defective in random plasmid integration, defective in DSB repair following IR, and radiosensitive, phenotypes similar to that of Ku70 knockdown cells. These findings identify Par3 as a novel component of the DNA-PK complex and implicate an unexpected link of cell polarity to DSB repair. PMID- 17287831 TI - Developmental expression of cyclin H and Cdk7 in zebrafish: the essential role of cyclin H during early embryo development. AB - Cyclin-dependent kinase 7 (Cdk7) is the catalytic subunit of the metazoan Cdk activating kinase (CAK). Activation of Cdk7 requires its association with a regulatory subunit, Cyclin H. Although the Cdk7/Cyclin H complex has been implicated in the regulation of RNA polymerase in several species, the precise function of their orthologs in zebrafish has not been fully elucidated. In this study, we isolated from zebrafish blastula embryos two cDNAs encoding the orthologs of human Cyclin H and Cdk7, and examined the role of Cdk7/Cyclin H in zebrafish embryogenesis. Sequence analysis showed that the zebrafish Cyclin H and Cdk7 cDNAs encode proteins with 65% and 86% identity to the respective human orthologs. RT-PCR and whole-mount in situ hybridization analyses of their expression in unfertilized eggs, embryos and organs of adult fish suggested that Cyclin H and Cdk7 messages are maternally loaded. Our data also showed that their transcripts were detected throughout development. Distribution of Cyclin H transcripts was found to be ubiquitous during early stages of development and become restricted to the anterior neural tube, brain, eyes, procreate tissues, liver and heart by 5 days post-fertilization. Expression of a dominant-negative form of Cyclin H delayed the onset of zygotic transcription in the early embryo, resulting in apoptosis at 5 hours post-fertilization and leading to sever defects in tissues normally exhibiting high levels of Cyclin H expression. These results implicate Cyclin H in the regulation of the transcriptional machinery during midblastula transition and suggest that it is an essential gene in early zebrafish larval development. PMID- 17287832 TI - Association of body weight with sexual function in women. AB - Sexual difficulties in women appear to be widespread in society; the relationship between female sexual function and obesity is unclear. This study aimed to investigate the relationship between body weight, the distribution of body fat and sexual function in women. Fifty-two, otherwise healthy women with abnormal values of female sexual function index (FSFI) score (< or =23) were compared with 66 control women (FSFI >23), matched for age and menopausal status. All women were free from diseases known to affect sexual function. FSFI strongly correlated with body mass index (BMI) (r=-0.72, P=0.0001), but not with waist-to-hip ratio (r=-0.09, P=0.48), in women with sexual dysfunction. Of the six sexual function parameters, desire and pain did not correlate with BMI, while arousal (r=-0.75), lubrication (r=-0.66), orgasm (r=-0.56) and satisfaction (r=-0.56, all P<0.001) did. FSFI score was significantly lower in overweight women as compared with normal weight women, while cholesterol and triglyceride levels were higher. On multivariate analysis, both age and BMI explained about 68% of FSFI variance, with a primacy of BMI over age (ratio 4:1). In conclusion, obesity affects several aspects of sexuality in otherwise healthy women with sexual dysfunction. PMID- 17287833 TI - Mode of delivery and subsequent long-term sexual function of primiparous women. AB - Minimal information exists on unintended health consequences following childbirth, particularly in relation to mode of delivery. This study aimed to evaluate the impact of mode of delivery on long-term sexual satisfaction of women by using a validated questionnaire. Forty-five primiparous women who had cesarean deliveries and 90 primiparous women who had vaginal deliveries with mediolateral episiotomies enrolled in the study. Quality of sexual relations and sexual satisfaction were self-reported by using Golombock-Rust Inventory of Sexual Satisfaction. Prevalence of sexual dissatisfaction was compared between the two groups and logistic regression analysis was carried out to identify the predictors of sexual dissatisfaction. The prevalence of overall sexual dissatisfaction was 4.4% in cesarean group while it was 14.4% in vaginal delivery group (P=0.081). Vaginal delivery group demonstrated a trend toward higher prevalence of dissatisfaction in all subscales except sensuality area than cesarean group, however, differences between two groups did not reach to statistical significance. Degree of pleasure for relationship with the spouse was identified as a significant predictor for overall sexual dissatisfaction (P=0.008). Our findings suggest that sexual dissatisfaction should not be assumed simply a product of the delivery mode. Individual, socio-demographic, lifestyle and marital characteristics should also be taken into account. PMID- 17287834 TI - Post-marketing surveillance study of the efficacy and safety of vardenafil among patients with erectile dysfunction in primary care. AB - To evaluate the safety and efficacy of vardenafil in primary care, we undertook a post-marketing surveillance study in 384 men with erectile dysfunction (ED), enrolled by 22 family physicians in Korea, from July 2004 to August 2005. Of the 384 patients enrolled, 343 (89.3%) returned for efficacy assessment and safety evaluation. Among the latter, 279 patients (81.3%) reported that their erectile function improved, 292 (92.1%) showed enhanced IIEF (International Index of Erectile Function)-5 scores and 265 (77.9%) responded that they were 'very satisfied' or 'satisfied' with vardenafil treatment. The most frequent reason for patient satisfaction with vardenafil was erectile potency (62.4%), followed by safety (42.4%), rapid onset (35.3%), adequate duration of efficacy (28.5%) and easy administration (25.9%). A total of 23 adverse events were observed in 18 patients, with the most frequent being hot flushes (3.2%), followed by headache (1.2%), nasal congestion (0.6%), color vision disturbance (0.3%), dizziness (0.3%), dry mouth (0.3%), dyspepsia (0.3%), nausea (0.3%) and diarrhea (0.3%). Only one patient discontinued vardenafil as a direct result of an adverse event. These results suggest that vardenafil prescribed by primary care physicians improved erectile function and was well tolerated by patients with ED. PMID- 17287836 TI - The methionine synthase polymorphism c.2756A>G (D919G) influences diastolic blood pressure. PMID- 17287837 TI - Endothelial function in normotensive and high-normal hypertensive subjects. AB - To evaluate the impact of a mild increment in blood pressure level on endothelial function, we evaluated 61 healthy volunteers (24 women, 37 men, and aged 35-50 years). All subjects underwent a blood chemistry panel to exclude any metabolic abnormalities and were submitted to a Doppler ultrasound of the brachial artery to assess endothelial function. We assessed the endothelial response to reactive hyperaemia and exogenous nitric oxide administration considering an increase in systolic blood pressure (SBP) at each 10-mm Hg interval. Our study population was divided as follows: SBP <115 mm Hg (SG1, n=13), SBP > or =115 mm Hg and <125 mm Hg (SG2, n=20), SBP > or = 125 mm Hg and <135 mm Hg (SG3, n=13) and SBP > or = 135 mm Hg and < 140 mm Hg (SG4, n=15). We found a significant difference in flow mediated dilation among SG2, SG3 and SG4, 16.2+/-5.6, 13.4+/-5.2 and 11.5+/-3.6%, P<0.05, respectively). After nitrate administration, we observed a nonsignificant decrease in brachial artery dilation among groups, P=0.217. Our data showed in a healthy normotensive population, without any risk factor for atherosclerotic disease that small increases in SBP but not in diastolic blood pressure may impair endothelial function even in subjects considered as high-normal, meaning that this population deserves more attention than usually ascribed to intervene and prevent complications, as endothelial dysfunction may represent an early change in those who develop hypertension later in life. PMID- 17287835 TI - Ageing causes cytoplasmic retention of MaxiK channels in rat corporal smooth muscle cells. AB - The MaxiK channel plays a critical role in the regulation of corporal smooth muscle tone and thereby erectile function. Given that ageing results in a decline in erectile function, we determined changes in the expression of MaxiK, which might impact erectile function. Quantitative-polymerase chain reaction demonstrated that although there is no significant change in transcription of the alpha- and beta-subunits that comprise the MaxiK channel, there are significant changes in the expression of transcripts encoding different splice variants. One transcript, SV1, is 13-fold increased in expression in the ageing rat corpora. SV1 has previously been reported to trap other isoforms of the MaxiK channel in the cytoplasm. Correlating with increased expression of SV1, we observed in older rats there is approximately a 13-fold decrease in MaxiK protein in the corpora cell membrane and a greater proportion is retained in the cytoplasm (approximately threefold). These experiments demonstrate that ageing of the corpora is accompanied by changes in alternative splicing and cellular localization of the MaxiK channel. PMID- 17287838 TI - Baroreflex sensitivity is impaired in essential hypertensives with central obesity. AB - Recently, much interest has focussed on the potential interaction between sympathetic nervous system and global cardiovascular risk. We investigated how baroreflex sensitivity (BRS), an index of autonomic function, interacts with central obesity (CO) in an essential hypertensive (EH) population. We selected 170 EHs and 43 normotensives (NT), (median age 47.3+/-11.3 and 49.1+/-13 years, respectively). Anthropometric parameters were measured for each and BRS was evaluated by a non-invasive method using Portapres TNO. The BRS evaluation was made using the sequences method. Systolic blood pressure (SBP) and heart rate were significantly higher in EH (P<0.001 and P=0.007, respectively). BRS was significantly greater in NT (P=0.02), and was associated inversely with waist circumference (WC) (P=0.005), but not with SBP or with other metabolic risk factors. Body mass index, total and high-density lipoprotein cholesterol, age and WC were not significantly different between the two groups. These results were confirmed by age pounded analysis. Finally, a separate analysis of the hypertensive group with CO (n=84) demonstrated a significantly lower BRS compared with the other hypertensive patients (n=86) (P<0.001). BRS is associated with WC but not with arterial pressure values and metabolic risk factors. Hypertensive subjects with CO show an impairment of BRS. Owing to its association with abdominal fat distribution and subsequently insulin resistance, BRS could represent a further and reliable index for evaluation of global cardiovascular risk in hypertensive patients. PMID- 17287839 TI - New insights into complement C3 and inflammation in hypertension. PMID- 17287840 TI - Systolic blood pressure and cardiac mortality over 24 years after venous coronary bypass surgery. PMID- 17287841 TI - Attitudes to and application of the concept of overall cardiovascular risk: comparison of male and female primary care providers. AB - The aim of this observational study was to assess whether there were differences in perception of overall cardiovascular risk (OCVR) in hypertensive patients depending on the gender of the primary care provider (PCP). We performed this study in 2003: 2979 male PCPs (MPCPs) and 562 female PCPs (FPCPs) participated throughout France. The patients included were hypertensive either treated or untreated, uncontrolled (blood pressure (BP) >or=140/90 mm Hg) with at least one other cardiovascular risk factor (CVRF) associated. OCVR of patients was both calculated according to French Agence Nationale d'Accreditation et d'Evaluation en Sante guidelines for uncontrolled hypertensive patients and subjectively estimated by the PCP as 'low', 'moderate', 'high' or 'very high'. About 11 770 patients were included, mean age was 63.7+/-11.2 years and 54.1% were men. Mean BP was 157+/-13/90+/-9 mm Hg. According to French guidelines, the calculated OCVR was 'moderate' in 23.7% of patients, 'high' in 47.5% and 'very high' in 28.8%. The PCP perceived OCVR was that 9.1% of patients were considered to be at 'low risk', 40.7% at 'moderate risk', 38.1% at 'high risk', and only 11.2% at 'very high risk' (OCVR was not estimated for 0.9% of patients). The overall agreement rate between the PCPs' estimation of OCVR and its calculation was 43.5%. Thus, in spite of extensive diffusion of ANAES guidelines, we found that PCPs in France generally underestimated OCVR though there were no significant differences between male and female physicians (45% for FPCPs and 43.2% for MPCPs). PMID- 17287842 TI - Reducing the burden of arterial hypertension: what can be expected from an improved access to health care? Results from a study in 2420 unemployed subjects in the Caribbean. AB - High prevalence and poor control of hypertension have been observed in populations with low-socioeconomic status. Comparing an unemployed population with another employed population sharing the same culture, and another employed population living in another environment might enlighten the effects of factors accessible to primary prevention on the one hand and access to health care on the other hand. The objectives are, first, to describe blood pressure (BP) prevalence and control in an unemployed Caribbean population benefiting from State financial support and good access to health care and second, compare the results in this population with those observed, with the same methodology in two employed populations, one in the Caribbean and one in metropolitan France. A cross sectional study of 2420 consecutive unemployed subjects referred for check-up in the two health centres of Guadeloupe, a French Caribbean island. Hypertension prevalence was 25.2% in men and 22.1% in women. BP was controlled in 17.3% of men and 37.2% of women receiving antihypertensive medication. Among women, 58% were overweight and 29% obese. Prevalence of hypertension was higher among the unemployed and employed Caribbean population, than among an employed metropolitan French population. A high prevalence of obesity was observed in the two Caribbean populations suggesting the interest of primary prevention in the Caribbean. Burden of hypertension in a population relates to the development of hypertension (primary prevention) and control of hypertension (secondary prevention). Identifying hypertensive patients and controlling blood pressure are both important to reduce the disease burden. PMID- 17287843 TI - Shear stress increases Cu/Zn SOD activity and mRNA expression in human endothelial progenitor cells. AB - Endothelial progenitor cells (EPCs) are involved in endothelial repair. However, the function of EPCs is impaired in the presence of cardiovascular risk factors. Therefore, upregulation of functional gene expression and bioactive substance production such as superoxide dismutase (SOD) activity and mRNA expression in EPCs may contribute to the maintenance of EPC-related endothelial repair. EPCs from human peripheral blood mononuclear cells were exposed to in vitro 5, 15 and 25 dyn/cm(2) shear stress for 5, 15 and 25 h, respectively. Shear stress in a dose- and time-dependent fashion increased Cu/Zn SOD activity of human EPCs. Shear stress also upregulated the Cu/Zn SOD mRNA expression of human EPCs, indicating that an increase in Cu/Zn SOD activity induced by shear stress was mediated by enhanced transcription. Our data are the first time to show that in vitro shear stress enhances mRNA expression and activity of Cu/Zn SOD in human EPCs, suggesting that shear stress can be used as a novel Means of manipulation to improve functional potential of EPCs. The augmentation in copper/zinc containing enzyme (Cu/Zn SOD), with subsequent accelerated superoxide anion (O(2)(-)) inactivation, might increase locally nitric oxide (NO) biological availability, which contributes to EPC-related vascular protection. PMID- 17287844 TI - Coronary heart disease and associated risk factors in sub-Saharan Africans. PMID- 17287845 TI - Hypertension in the elderly: a compelling contraindication for beta-blockers? PMID- 17287846 TI - Pulse transit time ratio as a potential marker for paediatric crural and brachial blood pressure index. PMID- 17287847 TI - Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. AB - Our objective was to review all published trials of coenzyme Q10 for hypertension, assess overall efficacy and consistency of therapeutic action and side effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study and eight open label studies. In the randomized controlled trials (n=120), systolic blood pressure in the treatment group was 167.7 (95% confidence interval, CI: 163.7-171.1) mm Hg before, and 151.1 (147.1-155.1) mm Hg after treatment, a decrease of 16.6 (12.6-20.6, P<0.001) mm Hg, with no significant change in the placebo group. Diastolic blood pressure in the treatment group was 103 (101-105) mm Hg before, and 94.8 (92.8-96.8) mm Hg after treatment, a decrease of 8.2 (6.2 10.2, P<0.001) mm Hg, with no significant change in the placebo group. In the crossover study (n=18), systolic blood pressure decreased by 11 mm Hg and diastolic blood pressure by 8 mm Hg (P<0.001) with no significant change with placebo. In the open label studies (n=214), mean systolic blood pressure was 162 (158.4-165.7) mm Hg before, and 148.6 (145-152.2) mm Hg after treatment, a decrease of 13.5 (9.8-17.1, P<0.001) mm Hg. Mean diastolic blood pressure was 97.1 (95.2-99.1) mm Hg before, and 86.8 (84.9-88.8) mm Hg after treatment, a decrease of 10.3 (8.4-12.3, P<0.001) mm Hg. We conclude that coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side effects. PMID- 17287848 TI - Use of beta-blockers for uncomplicated hypertension in the elderly: a cause for concern. AB - Beta-blockers are less beneficial than other antihypertensive drugs in the elderly with hypertension. All elderly patients in Ontario, Canada (population over 3.5 million elderly) without co-morbidities who were first treated for hypertension with a beta-blocker were studied in a retrospective population-based cohort study (1994-2002) to determine the characteristics of those prescribed beta-blockers. Of the 194,761 patients in our cohort, 25 485 (13%) were prescribed a beta-blocker as their first antihypertensive agent. On multivariate analysis, factors significantly associated with being prescribed a beta-blocker as first-line therapy included male sex (adjusted odds ratio (OR) 1.06 [95% CI 1.03-1.09] vs women), younger age (adjusted OR 1.67 [95% CI 1.55-1.79] for patients aged 66-69 vs those aged 85 or older), residence in a long-term care facility (adjusted OR 1.19 [95% CI 1.04-1.35] vs living in the community) and lower socioeconomic status (adjusted OR 1.07 [95% CI 1.02-1.12], for lowest quintile vs highest quintile). Patients with diabetes were substantially less likely to be prescribed beta-blockers (adjusted OR 0.42 [95% CI 0.40-0.44]). Greater efforts are required to educate physicians to select other drugs for initial therapy in older patients with uncomplicated hypertension. PMID- 17287849 TI - Highly purified CD38+ and CD38- sub-clones derived from the same chronic lymphocytic leukemia patient have distinct gene expression signatures despite their monoclonal origin. AB - CD38 expression is an important prognostic marker in chronic lymphocytic leukemia (CLL) with high levels of CD38 associated with shorter overall survival. In this study, we used gene expression profiling and protein analysis of highly purified cell-sorted CD38(+) and CD38(-) chronic lymphocytic leukemia cells to elucidate a molecular basis for the association between CD38 expression and inferior clinical outcome. Paired CD38(+) and CD38(-) CLL cells derived from the same patient were shown to be monoclonal by V(H) gene sequencing but despite this, CD38(+) CLL cells possessed a distinct gene expression profile when compared with their CD38( ) sub-clones. Importantly, CD38(+) CLL cells relatively over expressed vascular endothelial growth factor (VEGF) and appeared to preferentially utilize an internal autocrine VEGF survival loop. Elevated VEGF expression was associated with increased expression of the anti-apoptotic protein Mcl-1. Inhibition of VEGF receptor signaling also resulted in a reduction in cell viability. In contrast, exogenous VEGF caused a significant increase in CD38(-) CLL cell viability and a marked induction of Mcl-1; both effects were less obvious in CD38(+) CLL cells. Taken together, our data provide a biological rationale for the poor prognosis of CD38(+) CLL and indicate that both VEGF and Mcl-1 may prove to be useful therapeutic targets. PMID- 17287850 TI - Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. AB - Most modern treatment protocols for acute lymphoblastic leukaemia (ALL) include the analysis of minimal residual disease (MRD). To ensure comparable MRD results between different MRD-polymerase chain reaction (PCR) laboratories, standardization and quality control are essential. The European Study Group on MRD detection in ALL (ESG-MRD-ALL), consisting of 30 MRD-PCR laboratories worldwide, has developed guidelines for the interpretation of real-time quantitative PCR-based MRD data. The application of these guidelines ensures identical interpretation of MRD data between different laboratories of the same MRD-based clinical protocol. Furthermore, the ESG-MRD-ALL guidelines will facilitate the comparison of MRD data obtained in different treatment protocols, including those with new drugs. PMID- 17287852 TI - Activation of the c-myc p1 promoter in Burkitt's lymphoma by the hs3 immunoglobulin heavy-chain gene enhancer. AB - The expression of c-myc is deregulated in Burkitt's lymphoma by the translocation t(8;14). Most of the increased c-myc expression is from the P1 promoter, which is normally a minor promoter. How the P1 promoter is activated by the immunoglobulin heavy chain gene enhancers is not understood. We identified a YY1 site in the immunoglobulin heavy-chain gene HS3 enhancer, which increased c-myc P1 promoter activity, and a MARE site, which decreased c-myc P1 activity. Small Maf proteins bound to the MARE site both in vitro and in vivo, recruited histone deacetylase 2, and resulted in deacetylation of histones H3 and H4 at the c-myc promoter region. In contrast, YY1 recruited CBP and increased histone acetylation at the c myc promoter. Rb interacts with YY1 to prevent DNA binding in normal B cells, but no significant interaction with YY1 was detected in Burkitt's cells, and binding of YY1 to the HS3 enhancer was observed by chromatin immunoprecipitaton. Increased expression of MafK and/or decreased expression of YY1 by silencing RNA downregulated endogenous c-myc mRNA levels and increased the sensitivity of the cells to doxorubicin. Mutation of the major active sites (nuclear factor-kappa B and YY1) in the enhancers prevented c-myc activation. PMID- 17287851 TI - HTLV-I infection of WE17/10 CD4+ cell line leads to progressive alteration of Ca2+ influx that eventually results in loss of CD7 expression and activation of an antiapoptotic pathway involving AKT and BAD which paves the way for malignant transformation. AB - Adult T-cell leukemia/lymphoma (ATLL) is a malignancy slowly emerging from human T-cell leukemia virus type 1 (HTLV-I)-infected mature CD4(+) T-cells. To characterize the molecular modifications induced by HTLV-I infection, we compared HTLV-I-infected WE17/10 cells with control cells, using micro-arrays. Many calcium-related genes were progressively downmodulated over a period of 2 years. Infected cells acquired a profound decrease of intracellular calcium levels in response to ionomycin, timely correlated with decreased CD7 expression. Focusing on apoptosis-related genes and their relationship with CD7, we observed an underexpression of most antiapoptotic genes. Western blotting revealed increasing Akt and Bad phosphorylation, timely correlated with CD7 loss. This was shown to be phosphatidylinositol 3-kinase (PI3K)-dependent. Activation of PI3K/Akt induced resistance to the apoptotic effect of interleukin-2 deprivation. We thus propose the following model: HTLV-I infection induces a progressive decrease in CD3 genes expression, which eventually abrogates CD3 expression; loss of CD3 is known to perturb calcium transport. This perturbation correlates with loss of CD7 expression and induction of Akt and Bad phosphorylation via activation of PI3K. The activation of the Akt/Bad pathway generates a progressive resistance to apoptosis, at a time HTLV-I genes expression is silenced, thus avoiding immune surveillance. This could be a major event in the process of the malignant transformation into ATLL. PMID- 17287853 TI - A novel NUP98-PHF23 fusion resulting from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia. PMID- 17287854 TI - Acute lymphoblastic leukemia with t(4;11) in children 1 year and older: The 'big sister' of the infant disease? AB - The t(4;11)-positive acute lymphoblastic leukemia (ALL) is a rare disease in children above the age of 1 year. We studied the clinical and biological characteristics in 32 consecutively diagnosed childhood cases (median age 10.0 years, range 1.0-17.1 years). Immunophenotyping revealed a pro-B and a pre-B stage in 24 and eight cases, respectively. IGH genes were rearranged in 84% of leukemias with a predominance of incomplete DJ(H) joints. Whereas IGK-Kde and TCRD rearrangements were rare, TCRG rearrangements were present in 50% of cases and involved mainly Vgamma11 or Vgamma9 together with a Jgamma1.3./2.3 gene segment, an unusual combination among t(4;11)-negative B-cell precursor ALL. Oligoclonality was found in about 30% as assessed by heterogeneous IGH and TCRG rearrangements. Our data are in line with transformation of a precursor cell at an early stage of B-cell development but retaining the potential to differentiate to the pre-B cell stage in vivo. Although a distinct difference between infant and older childhood cases with t(4;11) became evident, no age-related biological features were found within the childhood age group. In contrast to infants with t(4;11)-positive ALL, childhood cases had a relatively low cumulative incidence of relapse of 25% at 3.5 years with BFM-based high-risk protocols. PMID- 17287855 TI - Fatigue in older adults with acute myeloid leukemia: predictors and associations with quality of life and functional status. PMID- 17287856 TI - IgM-expressing Waldenstrom's macroglobulinemia tumor cells reveal a potential for isotype switch events in vivo. PMID- 17287857 TI - Optimization of PCR-based minimal residual disease diagnostics for childhood acute lymphoblastic leukemia in a multi-center setting. AB - Minimal residual disease (MRD) diagnostics is used for treatment stratification in childhood acute lymphoblastic leukemia. We aimed to identify and solve potential problems in multicenter MRD studies to achieve and maintain consistent results between the AIEOP/BFM ALL-2000 MRD laboratories. As the dot-blot hybridization method was replaced by the real-time quantitative polymerase chain reaction (RQ-PCR) method during the treatment protocol, special attention was given to the comparison of MRD data obtained by both methods and to the reproducibility of RQ-PCR data. Evaluation of all key steps in molecular MRD diagnostics identified several pitfalls that resulted in discordant MRD results. In particular, guidelines for RQ-PCR data interpretation appeared to be crucial for obtaining concordant MRD results. The experimental variation of the RQ-PCR was generally less than three-fold, but logically became larger at low MRD levels below the reproducible sensitivity of the assay (<10(-4)). Finally, MRD data obtained by dot-blot hybridization were comparable to those obtained by RQ-PCR analysis (r(2)=0.74). In conclusion, MRD diagnostics using RQ-PCR analysis of immunoglobulin/T-cell receptor gene rearrangements is feasible in multicenter studies but requires standardization; particularly strict guidelines for interpretation of RQ-PCR data are required. We further recommend regular quality control for laboratories performing MRD diagnostics in international treatment protocols. PMID- 17287858 TI - Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients. AB - The spectrum of CBFB-MYH11 fusion transcripts in acute myeloid leukemia (AML) M4eo with inv(16)/t(16;16) is heterogeneous. Approximately 85% show type A CBFB MYH11 fusion transcripts. In addition, more than 10 different fusion transcripts have been reported. The prognostic impact and biological background of rare fusion transcripts remain open. In this study, a molecular characterization of CBFB-MYH11 transcripts in 162 patients with CBFB-MYH11 positive AML at diagnosis was performed. In total, 128 patients (79.0%) showed the fusion transcript type A, whereas nine different rare CBFB-MYH11 fusion genes were detected in 34 cases (21.0%). Rare fusion transcripts were found more frequently in therapy-related AML (P=0.0106). Numerical gains of the chromosomes 8, 21 and 22 were more frequently associated with type A (28.3%) than with rare fusions (12.9%) (P=0.012). Median white blood cell (WBC) count was higher in type A (35.4 G/l; range=1.1-279 G/l) than in cases with rare types (7.8 G/l; range=0.8-148.0 G/l) (P<0.0001). Rare fusion transcripts were correlated with an atypical cytomorphology not primarily suggestive for the FAB subtype M4eo (P=0.0203). Immunophenotype revealed lower CD2, CD13, CD33 and CD90 levels than in type A fusion cases (P=0.036, 0.002, 0.029 and 0.045, respectively). However, the type of fusion was not an independent prognostic parameter. PMID- 17287859 TI - Bifunctional compounds for targeted hepatic gene delivery. AB - A series of bifunctional compounds with galactosyl residues as targeting ligand for asialoglycoprotein receptors on hepatocytes and various dendrimers as the DNA binding domain was synthesized. When mixed with plasmid DNA, these compounds self assembled into particles that exhibited high transfection activity both in vitro and in vivo. Optimal activity in liver cells was observed with compounds containing three galactosyl residues and 16 dendrimer arms. These results suggest that domain-based design is an effective strategy for development of a new generation of synthetic gene carriers. PMID- 17287860 TI - Isolated limb perfusion: a novel delivery system for wild-type p53 and fiber modified oncolytic adenoviruses to extremity sarcoma. AB - Isolated limb perfusion (ILP) is a limb salvage surgical modality used to deliver chemotherapy and biologic agents to locally advanced and recurrent extremity soft tissue sarcoma (STS), and may be readily tailored for delivery of gene therapy. We set out to test the feasibility of delivering AdFLAGp53 (replication incompetent adenovirus bearing FLAG-tagged wild-type p53) and Ad.hTC.GFP/E1a.RGD (a fiber-modified, replication selective oncolytic adenovirus) into human leiomyosarcoma xenografts by ILP. Nude rats bearing SKLMS-1 tumors in their hind limbs underwent ILP with escalating doses of AdLacZ or AdFLAGp53 (study 1), or with Ad.CMV.GFP.RGD or Ad.hTC.GFP/E1a.RGD (study 2) following in vitro confirmation of therapeutic potential in STS cell lines and strains. Seventy-two hours after delivery, reverse transcription-polymerase chain reaction confirmed FLAGp53 expression, and immunohistochemistry confirmed diffuse upregulation of p21CIP1/WAF1 in ILP-treated tumors. Ad.hTC.GFP/E1a.RGD perfused tumors demonstrated robust macroscopic transgene expression throughout their substance, but not in perfused normal tissues, 21 days after delivery. Intra-tumoral viral replication was confirmed by immunohistochemical staining for early (E1a) and late (hexon) viral protein expression. Terminal deoxynucleotidyl transferase mediated-digoxigenin nick end-labeling staining identified foci of cell death within regions of viral replication. In conclusion, therapeutic adenoviral gene therapy against limb borne human STS can be successfully delivered by ILP and warrants further investigation. PMID- 17287862 TI - Live surgical demonstration: is it worthwhile? PMID- 17287861 TI - Mannan-modified adenovirus as a vaccine to induce antitumor immunity. AB - Tumor vaccine is a useful strategy for cancer therapy. However, priming of the immune system requires the relevant antigen to be presented by antigen-presenting cells (APCs). Here, we employed telomerase reverse transcriptase as a model antigen to explore the feasibility of using mannan-modified adenovirus as a tumor vaccine. We found that tumor immunogene therapy with the vaccine was effective at protective antitumor immunity in mice. The antigen-specific cytotoxic T lymphocytes were found in in vitro cytotoxicity assay. The elevation of the killing activity could be abrogated by anti-CD8 or anti-major histocompatibility complex-I antibodies. Adoptive transfer of purified CD8+ cells, and CD4+ cells to a less extent, was effective at antitumor activity. In vivo antitumor activity could be abrogated by depleting CD4+ T lymphocytes. A possible explanation for the antitumor effects may be the antigen was transferred to APCs in the presence of mannan. These observations provide insights into the design of novel vaccine strategies and might be important for the future application of antigens identified in other diseases. PMID- 17287863 TI - Mapping studies and modified templates in nonseminomatous germ cell tumors. PMID- 17287864 TI - Promise for patients with metastatic renal cell carcinoma. PMID- 17287865 TI - Antiangiogenic therapy in renal cell carcinoma: from concept to reality. PMID- 17287866 TI - Does periprostatic nerve block with local anesthetic reduce pain during prostate biopsy? PMID- 17287867 TI - Can a restaging transurethral resection predict early progression in patients with superficial bladder cancer? PMID- 17287868 TI - Is sentinel node biopsy indicated in penile cancer? PMID- 17287869 TI - Biologic agents as adjunctive therapy for prostate cancer: a rationale for use with androgen deprivation. AB - The prevalence of prostate cancer emphasizes the need for improved therapeutic options, particularly for metastatic disease. Current treatment includes medical or surgical castration, which initially induces apoptosis of prostate cancer cells, but ultimately an androgen-independent subpopulation emerges. In addition to a transient therapeutic effect, androgen-deprivation therapy (ADT) can initiate biochemical events that may contribute to the development of and progression to an androgen-independent state. This transition involves multiple signal transduction pathways that are accompanied by many biochemical changes resulting from ADT. These molecular events themselves are therapeutic targets and serve as a rationale for adjunctive treatment at the time of ADT. PMID- 17287870 TI - The medical management of Peyronie's disease. AB - There are a wide variety of medical treatments that are available to the practicing urologist, including oral agents, topical creams and gels with or without iontophoresis, intralesional injection therapy, radiation therapy, extracorporeal shockwave therapy, and laser therapy. Medical management of Peyronie's disease might be a valuable treatment option for this debilitating disorder, especially in the early symptomatic stages of the disease. Although no single modality has been demonstrated to have superior efficacy, intralesional therapy appears to confer some benefit. Multicenter, large-scale, randomized, controlled studies are necessary to fully establish the efficacy of the available treatments. Until such trials are conducted, a rational approach involving combination therapy is the most appropriate method to treat these patients. In this Review, the current medical treatment options available for the management of Peyronie's disease are discussed and a management algorithm is proposed. PMID- 17287871 TI - Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer. AB - Renal cell carcinoma (RCC) represents a group of diseases linked by their primary site of origin, the kidney. Studies of families with a genetic predisposition to the development of kidney cancer have revealed that multiple genes are involved in the molecular pathogenesis of RCC. Germline mutations in a gene that encodes a Krebs cycle enzyme have been found to result in a distinct clinical entity referred to as hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is inherited in an autosomal-dominant fashion. Affected individuals in HLRCC families are at risk for the development of leiomyomas of the skin and uterus as well as renal cancers. HLRCC-associated kidney tumors are often biologically aggressive. Linkage analysis has identified germline alterations in the fumarate hydratase (FH) gene associated with HLRCC. While the mechanisms of molecular carcinogenesis are not entirely understood, several lines of evidence derived from clinical and basic research suggest that pseudohypoxia might drive cellular transformation. The role of FH mutations in sporadic tumors seems to be limited. Nevertheless, continued investigation of HLRCC should provide further insight into the mechanisms of kidney cancer development, and could potentially identify targets for new therapeutic approaches to RCC. PMID- 17287872 TI - A case of prostatitis due to Burkholderia pseudomallei. AB - BACKGROUND: A 67-year-old male, with a history of stable lower urinary tract symptoms, diabetes mellitus, benign prostatic hyperplasia, gonococcal urethritis, and excessive alcohol consumption, presented to the emergency room with sepsis and acute bacterial prostatitis. He had recently returned from a visit to Indonesia, where he had been a first-hand witness to the 2004 tsunami. INVESTIGATIONS: Complete blood cell count, urine analysis, blood, urine, and prostatic abscess cultures, chest X-ray, contrasted CT of the abdomen and pelvis, and (18)F-fluorodeoxyglucose PET. DIAGNOSIS: Melioidosis. MANAGEMENT: Broad spectrum empiric antibiotics were administered initially; therapy was then changed to intravenous imipenem plus cilastatin with slow initial clinical improvement. (18)F-fluorodeoxyglucose PET localized the prostate as the only nidus of infection. Ultrasound-guided fine needle aspiration of a small fluid collection of the prostate also grew Burkholderia pseudomallei. The patient improved clinically and was discharged to complete a 2-week course of intravenous imipenem plus cilastatin followed by a 3-month course of oral trimethoprim plus sulfamethoxazole. This medication was switched to co-amoxiclav and doxycycline to complete the 3-month course. The patient was well at his last follow-up, 3 months following hospital discharge. PMID- 17287873 TI - Ultrafast dynamics of halogens in rare gas solids. AB - We perform time resolved pump-probe spectroscopy on small halogen molecules ClF, Cl2, Br2, and I2 embedded in rare gas solids (RGS). We find that dissociation, angular depolarization, and the decoherence of the molecule is strongly influenced by the cage structure. The well ordered crystalline environment facilitates the modelling of the experimental angular distribution of the molecular axis after the collision with the rare gas cage. The observation of many subsequent vibrational wave packet oscillations allows the construction of anharmonic potentials and indicate a long vibrational coherence time. We control the vibrational wave packet revivals, thereby gaining information about the vibrational decoherence. The coherence times are remarkable larger when compared to the liquid or high pressure gas phase. This fact is attributed to the highly symmetric molecular environment of the RGS. The decoherence and energy relaxation data agree well with a perturbative model for moderate vibrational excitation and follow a classical model in the strong excitation limit. Furthermore, a wave packet interferometry scheme is applied to deduce electronic coherence times. The positions of those cage atoms, excited by the molecular electronic transitions are modulated by long living coherent phonons of the RGS, which we can probe via the molecular charge transfer states. PMID- 17287874 TI - Scanning electrochemical microscopy in the 21st century. AB - The fundamentals of and recent advances in scanning electrochemical microscopy (SECM) are described. The focus is on applications of this method to studies of systems and processes of active current interest ranging from nanoelectrochemistry to electron transfer reactions and electrocatalysis to biological imaging. PMID- 17287875 TI - Adsorption of carbon monoxide on Li-ZSM-5: theoretical study of complexation of Li+ cation with two CO molecules. AB - The Li+ cation complexes with one and two CO molecules have been studied computationally. The calculations reveal the conditions when two CO molecules could bind to one Li+ cation in zeolite Li-ZSM-5. In the absence of dicarbonyls (at low adsorbate coverage or at high temperatures), the IR absorption bands can be assigned only on the basis of the Li+ coordination number to the framework oxygen atoms. PMID- 17287876 TI - Theoretical investigation of the EPR hyperfine coupling constants in amino derivatives. AB - The HFCCs of the radical cations of a series of amines have been determined at different levels of approximation including the CISD, QCISD, and CCSD ab initio correlated methods and density functional theory approaches employing the B3LYP, PBE0, BHandHLYP, TPSS, and BLYP exchange-correlation functionals. Although quantitative differences with respect to experimental data have been noticed, these are mostly systematic within a given class of N and H atoms. As a consequence, these different levels of theory are reliable in most cases to account for the substituent and structure effects on the HFCCs of amines. Linear regression fits have then been performed to reach quantitative agreement between the theoretical and experimental values. This has finally been substantiated by considering the EPR signal of the recently synthesized radical cations of two derivatives of [10-(4-aminophenyl)-9-anthryl]aniline as well as in confirming a recent assignment of the EPR signal of n-propylamine. PMID- 17287877 TI - Evidence for a C-H...pi type weak interaction: 1 : 1 complex of styrene with acetylene studied by mass selective high-resolution UV spectroscopy and ab initio calculations. AB - The 1 : 1 complex of styrene with acetylene has been studied by mass selective low- and high-resolution UV resonance-enhanced two-photon ionisation (R2PI) spectroscopy combined with genetic-algorithm-based computer-aided fit of the spectra with partial rotational resolution, and high level ab initio quantum chemistry calculations. Two stable conformeric geometries of the 1 : 1 complex of styrene and acetylene have been theoretically found: one with acetylene binding to styrene as a proton donor, and one with acetylene acting as a proton acceptor. From the analysis of the vibronic structure of the S1<-- S0 spectrum and the fit of the highly resolved spectrum of the 0 origin band of the complex it is shown that the favoured conformation is the one in which acetylene binds to the benzene ring of styrene through formation of a non-conventional hydrogen bond of C-H...pi type with no marked change of the transition moment orientation of styrene. The styrene moiety remains planar and the acetylene molecule is tilted by a small angle of 4 degrees relative to the C6 symmetry axis of the benzene ring, most likely due to the reduced symmetry of the benzene ring pi electrons rather than to a direct interaction with the vinyl group. PMID- 17287878 TI - Small gas-phase dianions of Zn3O(4)(2-), Zn4O(5)(2-), CuZn2O(4)(2-), Si2GeO(6)(2 ), Ti2O(5)(2-) and Ti3O(7)(2-). AB - We have searched for new species of small oxygen-containing gas-phase dianions produced in a secondary ion mass spectrometer by Cs+ ion bombardment of solid samples with simultaneous exposure of their surfaces to O2 gas. The targets were a pure zinc metal foil, a copper-contaminated zinc-based coin, two silicon germanium samples (Si(1-x)Ge(x)(with x= 6.5% or 27%)) and a piece of titanium metal. The novel dianions Zn3O(4)(2-), Zn4O(5)(2-), CuZn2O(4)(2-), Si2GeO(6)(2-), Ti2O(5)(2-) and Ti3O(7)(2-) have been observed at half-integer m/z values in the negative ion mass spectra. The heptamer dianions Zn3O(4)(2-) and Ti2O(5)(2-) have been unambiguously identified by their isotopic abundances. Their flight times through the mass spectrometer are approximately 20 micros and approximately 17 micros, respectively. The geometrical structures of the two heptamer dianions Ti2O(5)(2-), and Zn3O(4)(2-) are investigated using ab initio methods, and the identified isomers are compared to those of the novel Ge2O(5)(2-) and the known Si2O(5)(2-) and Be3O(4)(2-) dianions. PMID- 17287879 TI - Calculation of the vibrationally non-relaxed photo-induced electron transfer rate constant in dye-sensitized solar cells. AB - In this paper we shall show how to calculate the single vibronic-level electron transfer rate constant, which will be compared with the thermal averaged one. To apply the theoretical results to the dye-sensitized solar cells, we use a simple model to describe how we model the final state of the electron-transfer process. Numerical calculations will be performed to demonstrate the theoretical results. PMID- 17287880 TI - Steady state voltammetry at non-uniformly accessible electrodes: a study of Tafel plots for microdisc and tubular flow electrodes in the reversible and irreversible limits of electron transfer. AB - Steady state concentration profiles are obtained via numerical solution for an electron transfer at the microdisc and tubular flow electrodes. The non-uniform flux profiles over the electrode surfaces and their effect on the voltammetric waveshape are discussed. An approach is suggested for the most appropriate way to estimate the charge transfer coefficient from an experimental voltammogram of an irreversible electron transfer. PMID- 17287881 TI - Thermodynamic and aggregation properties of aza- and imino-substituted gemini surfactants designed for gene delivery. AB - Improving the efficiency of gene delivery by using non-viral vectors is currently an area of considerable research interest. Novel derivatives of gemini surfactants having aza- (12-5N-12, 12-7N-12, 12-8N-12) and imino- (12-7NH-12) substituted spacer groups and C12 tails have been designed to improve DNA transfection. Physicochemical characterization of micelle and interfacial properties of these cationic compounds are reported. The effect of these substitutions on the aggregation properties of the gemini surfactants is discussed in the context of results for the 12-s-12 and 12-EOx-12 gemini series, previously reported in the literature. Aza substitution results in a spacer of intermediate hydrophobicity to the above series, reflected by the magnitude of both the critical micelle concentrations and head group areas. Enthalpy and apparent molar volume of micellization data illustrate the differences in the aggregation properties that result from the bulkier and more hydrophobic aza substituent in the spacer as compared to an ether oxygen (for the 12-EOx-12 series) containing spacer. The 12-7N-12 and 12-8N-12 compounds show aberrant features in the surface tension and enthalpy of dilution results that are not observed for the 12-5N-12 and 12-7NH-12 compounds. Premicelle association is considered to be a source of this behaviour. PMID- 17287882 TI - Cu/ZnO and Cu/ZrO2 interactions studied by contact angle measurement with TEM. AB - A technique of contact angle measurement was applied to the nano-scale oxide supported metal particles. For Cu supported on ZnO and ZrO2 the angles were found to increase and the work of adhesion to decrease with increasing particle size. Such a trend is interpreted as an effect of negative contact line tension of 2.1 x 10(-9) J m(-1) and 1.0 x 10(-9) J m(-1) in the Cu/ZnO and Cu/ZrO2 system, correspondingly. For the small-sized Cu particles the apparent work of adhesion on ZnO support is higher than that on ZrO2. PMID- 17287883 TI - Enantioselective hydrogenation of ethyl pyruvate over diop modified Pt nanoclusters. Determination of geometry of the ligand adsorption mode via DRIFTS. AB - Immobilization of chiral ligands on the surface of metal nanoparticles is one concept for heterogenation of enantioselective catalysts. Diop modified Pt nanoclusters were found to be able to induce enantioselectivity and enhancement of the reaction rate in hydrogenation of ethyl pyruvate. The model of geometry of the diop adsorption has been proposed based on DRIFTS and molecular modelling investigations. The ability of diop to induce enantioselectivity and enhanced reaction rate was explained through the adsorption geometry and comparison with known models of enantioselectivity established for the cinchonidine on Pt system. PMID- 17287884 TI - Nano-structured support materials, their characterisation and serum protein profiling through MALDI/TOF-MS. AB - In the bioanalytical era, novel nano-materials for the selective extraction, pre concentration and purification of biomolecules prior to analysis are vital. Their application as affinity binding in this regard is needed to be authentic. We report here the comparative application of derivatised materials and surfaces on the basis of nano-crystalline diamond, carbon nanotubes and fullerenes for the analysis of marker peptides and proteins by material enhanced laser desorption ionisation mass spectrometry MELDI-MS. In this particular work, the emphasis is placed on the derivatization, termed as immobilised metal affinity chromatography (IMAC), with three different support materials, to show the effectiveness of MELDI technique. For the physicochemical characterisation of the phases, near infrared reflectance spectroscopy (NIRS) is used, which is a well-established method within the analytical chemistry, covering a wide range of applications. NIRS enables differentiation between silica materials and different fullerenes derivatives, in a 3-dimensional factor-plot, depending on their derivatizations and physical characteristics. The method offers a physicochemical quantitative description in the nano-scale level of particle size, specific surface area, pore diameter, pore porosity, pore volume and total porosity with high linearity and improved precision. The measurement takes only a few seconds while high sample throughput is guaranteed. PMID- 17287885 TI - Transgenic cotton over-producing spinach sucrose phosphate synthase showed enhanced leaf sucrose synthesis and improved fiber quality under controlled environmental conditions. AB - Prior data indicated that enhanced availability of sucrose, a major product of photosynthesis in source leaves and the carbon source for secondary wall cellulose synthesis in fiber sinks, might improve fiber quality under abiotic stress conditions. To test this hypothesis, a family of transgenic cotton plants (Gossypium hirsutum cv. Coker 312 elite) was produced that over-expressed spinach sucrose-phosphate synthase (SPS) because of its role in regulation of sucrose synthesis in photosynthetic and heterotrophic tissues. A family of 12 independent transgenic lines was characterized in terms of foreign gene insertion, expression of spinach SPS, production of spinach SPS protein, and development of enhanced extractable V (max) SPS activity in leaf and fiber. Lines with the highest V (max) SPS activity were further characterized in terms of carbon partitioning and fiber quality compared to wild-type and transgenic null controls. Leaves of transgenic SPS over-expressing lines showed higher sucrose:starch ratio and partitioning of (14)C to sucrose in preference to starch. In two growth chamber experiments with cool nights, ambient CO(2) concentration, and limited light below the canopy, the transgenic line with the highest SPS activity in leaf and fiber had higher fiber micronaire and maturity ratio associated with greater thickness of the cellulosic secondary wall. PMID- 17287886 TI - Bovine subclinical ketosis in dairy herds in Iran. AB - Subclinical ketosis (SCK) is defined as elevated concentrations of ketone bodies in the absence of clinical signs of ketosis. It is an important metabolic disease in dairy cattle during early lactation and is associated with losses in milk production and several other periparturient diseases. Limited information is available regarding the prevalence of SCK in dairy herds in Iran. The objectives of this study were (i) to determine the incidence of SCK in the dairy herds in Kerman province of Iran using serum beta-hydroxybutyrate (BHB) concentrations, and (ii) to investigate the relationship between serum concentrations of BHB and glucose of cows with SCK. In the present study, 90 multiparous Holstein cows (4-6 years old) from 11 commercial dairy herds were evaluated 3-4 weeks after calving. The distribution of blood BHB concentrations seemed to suggest a cut-off point of 1200 micromol/L between cows with and without SCK. At this cut-off point, 14.4% of tested cows (13/90) were classified as subclinically ketotic, with the prevalence rate within herd ranging from 10% to 20%. Cows with SCK were detected in all the investigated dairies except one. Blood glucose concentrations in cows with SCK were significantly lower (p < or = 0.05) than in cows without SCK, and serum BHB and glucose concentration were inversely correlated (r = -0.43, p < or = 0.05). The results suggest that, using a cut-off of 1200 micromol/L, BHB concentrations can be used during early lactation for diagnosis and to make management decisions for prevention and treatment. PMID- 17287887 TI - Effect of an immunosuppressor (dexamethasone) on eperythrozoon infection. AB - The aim was to study the relationship between the infection rate of Eperythrozoon suis and the status of the immune system. Four pigs with chronic eperythrozoonosis were divided into experimental and control groups. Immunosuppression of the experimental group was accomplished by injecting with high-dose glucocorticoid (dexamethasone) on 3 consecutive days. Microscopic examination of blood smears was performed to observe the change of infection rate after administration. The blood samples of each group were collected on day 7 after administration for half-nested PCR assay. The microscopic results showed that the infection rate of the experimental group rose distinctly by 40 h late and remained at 90% in the days following administration. No changes were observed in the control group. PCR results showed a single expected 250 bp fragment in each group, which validated the positive microscopic results. This study demonstrated the significant effect of dexamethasone (DEX) on Eperythrozoon infection. PMID- 17287888 TI - Therapeutic potentials of combined use of DMSA with calcium and ascorbic acid in the treatment of mild to moderately lead intoxicated mice. AB - The aim of this study was to explore the therapeutic efficacies of combined use of meso-2,3-dimercaptosuccinic acid (DMSA) with calcium and ascorbic acid in the treatment of mild to moderately lead-intoxicated mice. Female albino mice were exposed to lead by drinking water contaminated with 0.1% (moderate lead exposure) or 0.05% (mild lead exposure) lead acetate. After the cessation of lead exposure, mice were supplemented by gavage with saline solution, 50 mg/kg body weight (b.w) DMSA, 100 mg/kg b.w DMSA, calcium and ascorbic acid, or 50 mg/kg b.w DMSA and calcium as well as ascorbic acid, respectively. Atomic absorption spectrophotometric method was used to analyze lead levels in blood, bone, liver, kidney and brain. Activities of blood delta-aminolevulinic acid dehydratase (ALAD) were determined by colorimetric method. DMSA supplemented alone could reduce lead levels in both soft tissues and bone and reverse lead-inhibited activities of blood ALAD in mild to moderately lead-intoxicated mice. On the other hand, combined use of DMSA with calcium and ascorbic acid achieved better therapeutic efficacies in mobilizing lead in blood, liver and kidney, and reversing lead-inhibited activities of blood ALAD in moderately lead intoxicated mice than DMSA supplemented alone. Moreover, the better therapeutic efficacies were also found in mildly lead intoxicated mice in mobilizing lead in blood and bone achieved by combined use of DMSA with calcium and ascorbic acid. Combined use of DMSA with calcium and ascorbic acid seems to be the better choice in the treatment of mild to moderate lead-intoxication. PMID- 17287889 TI - Characterization of ferric-anguibactin transport in Vibrio anguillarum. AB - The fish pathogen Vibrio anguillarum is the causative agent of a fatal hemorrhagic septicemia in salmonid fish. Many serotype O1 strains harbors a 65 Kbp plasmid (pJM1 encoding an iron sequestering system essential for virulence. The genes involved in the biosynthesis of the indigenous siderophore anguibactin are encoded by both the pJM1 plasmid and the chromosome, while those involved in the transport of the ferric-siderophore complex, including the outer membrane receptor, are plasmid-encoded. This work describes the role of specific amino acid residues of the outer membrane receptor FatA in the mechanism of transport of ferric-anguibactin. FatA modeling indicated that this protein has a 22 stranded beta-barrel blocked by the plug domain, the latter being formed by residues 51-154. Deletion of the plug domain resulted in a receptor unable to act as an open channel for the transport of the ferric anguibactin complex. PMID- 17287891 TI - Gametophyte contribution to sporophyte growth on the basis of carbon gain in the fern Thelypteris palustris: effect of gametophyte organic-matter production on sporophytes. AB - At an early stage of growth gametophytes support the sporophytes of ferns. Young sporophytes become independent of gametophytes when the first leaves develop. Although large fern gametophytes produce multiple archegonia simultaneously, only one sporophyte is typically established on one gametophyte. The number of sporophytes is believed to be controlled in two possible directions, from gametophyte to sporophyte or from preceding sporophyte to another sporophyte. To investigate the effects of gametophytes on their sporophytes, we studied the relationship between organic matter production by gametophytes and the growth of young sporophytes of Thelypteris palustris. We cut gametophytes in half (CGs) to reduce the gametophytes' production of matter. There was no significant difference between the growth of sporophytes on intact gametophytes (IGs) and that on CGs. According to our estimates, based on the rate of organic matter production, the large gametophyte was able to produce two or more sporophytes. The resources required for CGs to make similar-sized sporophytes was twice that for IGs. In polyembryony each of the multiple sporophytes was similar in size to the single sporophytes. Resource limitation does not seem to explain why fern gametophytes establish single sporophytes. PMID- 17287892 TI - Root and vascular tissue-specific expression of glycine-rich protein AtGRP9 and its interaction with AtCAD5, a cinnamyl alcohol dehydrogenase, in Arabidopsis thaliana. AB - The vascular tissue of roots performs essential roles in the physical support and transport of water, nutrients, and signaling molecules in higher plants. The molecular mechanisms underlying the function of root vascular tissue are poorly understood. In this study, we analyzed the expression pattern of AtGRP9, a salt stress-responsive gene encoding a glycine-rich protein, and its interacting partner, in Arabidopsis thaliana. Analysis of GUS or GFP expression under the control of the AtGRP9 promoter showed that AtGRP9 was expressed in the vascular tissue of the root; subcellular localization analysis further demonstrated that AtGRP9 proteins were localized in the cell wall and in the cytoplasm. Yeast two hybrid analysis revealed that AtGRP9 interacted with AtCAD5, a major cinnamyl alcohol dehydrogenase (CAD) involved in lignin biosynthesis, for which tissue specific distribution was comparable with that of AtGRP9. These results suggest that AtGRP9 may be involved in lignin synthesis in response to salt stress as a result of its interaction with AtCAD5 in A. thaliana. PMID- 17287893 TI - Does oxidative stress participate in the development of hepatocellular carcinoma? PMID- 17287895 TI - Extracellular signal-regulated kinase 1- and 2-mediated gastric mucosal injury and repair in gastric ischemia-reperfusion of rats. AB - BACKGROUND: The current study was undertaken to investigate the time course of gastric ischemia-reperfusion (GI-R)-induced gastric mucosal injury and repair and whether extracellular signal-regulated kinase 1/2 (ERK1/2) were involved in GI-R induced gastric mucosal injury and repair. METHODS: Immunohistochemistry and Western blot analyses were used. RESULTS: Gastric mucosal injury induced by ischemia alone was mild. However, the injury worsened after reperfusion, reaching a maximum at 1 h, and was accompanied by increased apoptotic cells and decreased proliferative cells. Then, the gastric mucosal cells began to repair the injury by enhanced proliferation, which peaked at 24 h after reperfusion, and by 72 h the damaged gastric mucosa was mostly repaired. The ERK1/2 (nonactivated ERK1/2) protein expression level and distribution profile showed no significant changes during the entire reperfusion phase, but the p-ERK1/2 (activated ERK1/2) level changed dramatically. The p-ERK1/2 protein level was decreased at 0.5 h after reperfusion began, and then gradually increased, peaking after 3 h of reperfusion; these changes in p-ERK1/2 occurred simultaneously in the cytoplasm and nucleus. On the other hand, inhibition of the activation of ERK1/2, induced by PD98059, a specific ERK1/2 upstream inhibitor, aggravated the gastric mucosal injury, and apoptosis was increased and proliferation was reduced in the gastric mucosal cells after the same duration of reperfusion. CONCLUSIONS: Serious gastric mucosal damage involving apoptotic cells occurred rapidly at an early stage of reperfusion and was closely related to the suppression of ERK1/2 activation. The activated ERK1/2 signaling transduction pathway played an important role. Activated ERK1/2 participated in the regulation of gastric mucosal injury and repair induced by GI-R, and might be mediated by the inhibition of apoptosis and the promotion of proliferation in gastric mucosal cells. PMID- 17287894 TI - Schedule-dependent cytotoxicity of 5-fluorouracil and irinotecan in a colon cancer cell line. AB - BACKGROUND: Our aim was to clarify the significance of widely accepted irinotecan (CPT-11)/5-fluorouracil (5-FU) combinations in colon cancer by investigating their sequential effect. METHODS: The sequential effect of CPT-11/5-FU in two colon cancer cell lines, LoVo and SW480, was evaluated by WST-8 colorimetric assay. The cell cycle distributions of each drug were analyzed by flow cytometry, and then the chemoresistant mechanisms and expression of a drug transporter (MDR1), the bcl-2 apoptotic pathway, metabolizing enzymes [carboxylesterase (CE), dihydropyrimidine dehydrogenase], and target enzymes (topoisomerase I, thymidine synthase) associated with sequence-dependent cytotoxicity were examined. RESULTS: The cytotoxicity of 5-FU (10, 100, 1000 microM) followed by CPT-11 (1 microM) was significantly greater than that of CPT-11 (1 microM) followed by 5-FU (10, 100, 1000 microM) (P < 0.05). Reverse transcription-polymerase chain reaction analysis revealed that exposure to 5-FU downregulated both MDR1 and bcl-2 mRNA and simultaneously upregulated CE2 mRNA expression, suggesting enhancement of subsequent CPT-11 cytotoxicity. CONCLUSIONS: The cytotoxic effects of the CPT 11/5-FU combinations were shown to be schedule-dependent in human colon cancer cells. The findings suggest that 5-FU followed by CPT-11 administration might be the optimal sequence for CPT-11/5-FU treatment of advanced colon cancer. PMID- 17287896 TI - Helicobacter pylori infection in combination with the serum pepsinogen I/II ratio and interleukin-1beta-511 polymorphisms are independent risk factors for gastric cancer in Thais. AB - BACKGROUND: Thailand has the lowest incidence of gastric cancer in the world. Helicobacter pylori infection, a low serum pepsinogen I/II ratio, and interleukin (IL)-1beta-511 polymorphisms are suspected to be risk factors for gastric cancer. METHODS: A total of 167 Thais, comprising 56 cancer patients and 111 volunteers without cancer, underwent an esophagogastroduodenoscopic examination and three fixed-point biopsies; a cancer tissue biopsy was also done, and blood samples were collected. The subjects without cancer were divided into normal subjects and chronic gastritis patients. IL-1beta-511 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism, and the serum levels of pepsinogen I and II were determined by a radioimmunoassay. Helicobacter pylori IgG antibody and tissue pathology were tested in all groups. RESULTS: The pepsinogen I/II ratio was significantly lower in the gastric cancer group than in the normal and chronic gastritis groups [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.10-4.80; P = 0.025]. Gastric cancer patients were positive for the H. pylori IgG antibody more frequently than negative (OR, 2.946; 95% CI, 1.4 6.39; P = 0.005). However, only 15 (27%) cancer patients were both positive for H. pylori IgG antibody and had low serum pepsinogen I/II. The C/C genotype was found more frequently in the gastric cancer group than in the group with a normal gastric mucosa (OR, 0.64; 95% CI, 0.50-0.81; P = 0.014). CONCLUSIONS: A low serum pepsinogen I/II ratio combined with positivity for H. pylori IgG, and a IL-1beta 511 C/C genotype may be independent risk factors for gastric cancer in Thais. PMID- 17287897 TI - Assessing the efficacy of famotidine and rebamipide in the treatment of gastric mucosal lesions in patients receiving long-term NSAID therapy (FORCE--famotidine or rebamipide in comparison by endoscopy). AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are major causes of gastric mucosal lesions. In Japan, histamine-2 receptor antagonists are frequently prescribed, but the literature regarding their efficacy is limited. In this study, we compare the effects of famotidine and rebamipide on NSAID-associated gastric mucosal lesions using upper gastrointestinal endoscopy. METHODS: This study examined 112 patients taking NSAIDs for either gastric hemorrhage or erosion. Before treatment, the patients were assessed by endoscopy. Using blind randomization, patients were divided into two groups: group F (famotidine, 20 mg/day) and group R (rebamipide, 300 mg/day). Efficacy was examined 4 weeks later using endoscopy. RESULTS: After treatment, the Lanza score decreased significantly in group F (P < 0.001) but not in group R (P = 0.478). The change in the Lanza score in group F was significantly greater (P = 0.002) than that in group R. CONCLUSIONS: Famotidine was superior to rebamipide in treating NSAID-associated mucosal lesions. PMID- 17287898 TI - Early genetic instability of both epithelial and stromal cells in esophageal squamous cell carcinomas, contrasted with Barrett's adenocarcinomas. AB - BACKGROUND: We have shown previously that stromal genetic alteration may make a greater contribution to early genesis of ulcerative colitis-associated tumors than sporadic colon cancers. We assessed whether similar differences in genetic alteration might exist between squamous cell carcinomas (SCCs) and Barrett's adenocarcinomas (BACs) of the esophagus. METHODS: We investigated epithelial and stromal genetic instability with five National Cancer Institute standard (NCI), four chromosome 17 (Chr. 17), and six tumor suppressor gene (TSG) microsatellite markers in 26 SCC and 12 BAC cases and in 11 normal controls, using a novel combination of microdissection, polymerase chain reaction, and GeneScan. RESULTS: Frequency of epithelial loss of heterozygosity (LOH) increased in the order background mucosa, to precursor lesions, to tumors with both types of carcinoma, especially for the Chr. 17 and TSG markers, while stromal LOH was relatively high but consistent from background mucosa to carcinoma. Epithelial LOH of D17S796 demonstrated a significantly higher frequency in SCCs than in BACs, without significant variation in p53 overexpression. The frequency of microsatellite instability (MSI) showed constant high levels in both epithelium and stroma of background, dysplasia, and carcinomas in the SCC series, and rather low frequencies in the BAC series. Although epithelial hMLH1 and hMSH2 expression decreased with tumor progression, no correlation was found with the individual MSI status. CONCLUSIONS: Although epithelial LOH exists similarly in both lesion types, whereas epithelial and stromal MSI may occur in a relatively early phase of SCC development, stromal MSI is rare in BACs, strongly suggesting differences in tumorigenesis between the two types. PMID- 17287899 TI - Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. AB - BACKGROUND: Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by high serum IgG4 concentrations and abundant IgG4-bearing plasma cell infiltration in the pancreatic lesion, and it has been reported to be associated with a variety of extrapancreatic lesions, leading us to postulate the concept of a systemic inflammatory disease. To confirm this, we clarified the exact distribution of these extrapancreatic lesions and provide a panoramic view of them. METHODS: The frequency, distribution, clinical characteristics, and pathology of five extrapancreatic lesions were determined in 64 patients with autoimmune pancreatitis by examining clinical and laboratory findings. RESULTS: The most frequent extrapancreatic lesion was hilar lymphadenopathy (80.4%), followed by extrapancreatic bile duct lesions (73.9%), lachrymal and salivary gland lesions (39.1%), hypothyroidism (22.2%), and retroperitoneal fibrosis (12.5%). No patients had all five types of lesions. Patients with hilar lymphadenopathy or lachrymal and salivary gland lesions were found to have significantly higher IgG4 levels than those without (P = 0.0042 and 0.0227, respectively). Patients with three lesions were found to have significantly higher IgG4 levels than those with no lesion, suggesting that patients with multiple extrapancreatic lesions have active disease. Similar to pancreatic lesions, extrapancreatic lesions have a characteristic histological finding of abundant IgG4-bearing plasma cell infiltration, and they respond favorably to corticosteroid therapy. CONCLUSIONS: Autoimmune pancreatitis was recognized as a systemic inflammatory disease. Furthermore, recognition of these characteristic findings will aid in the correct diagnosis of this disease. PMID- 17287900 TI - Interferon lowers tumor recurrence rate after surgical resection or ablation of hepatocellular carcinoma: a pilot study of patients with hepatitis B virus related cirrhosis. AB - BACKGROUND: Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) often recurs after surgical or medical treatment. METHODS: Eighty consecutive patients with HBV-positive cirrhosis and HCC who underwent potentially curative ablation for HCC were analyzed. Eleven patients received long-term interferon (IFN) therapy. HBV DNA was quantified at the time of HCC treatment. A DNA value of <6.0 log copies/ml was considered low. RESULTS: Initial DNA was low in 39 and high in 41 patients. HCC recurrence rates in the low DNA group and high DNA group were 46.9% and 82.6% at the fifth year, and 73.5% and 91.3% at the tenth year, respectively (P = 0.0103). Similarly, recurrence rates after treatment of HCC in the normal aspartate aminotransferase (AST) group (<38 IU/l, n = 42) and abnormal AST group (n = 38) were 50.6% and 84.0% at the fifth year, and 71.3% and 100% at the tenth year, respectively (P = 0.0003). Six of the 38 patients with abnormal AST, and 5 of 42 patients with normal AST, received IFN after confirmation of tumor ablation. In the subgroup of abnormal AST, tumor recurrence rates in the IFN and untreated groups were 16.7% and 37.9% at the end of the first year, 16.7% and 60.1% at the second year, and 16.7% and 83.4% at the third year, respectively (P = 0.0139). Multivariate analysis revealed that IFN significantly reduced the recurrence rate (hazard ratio = 0.21, P = 0.037) even after adjusting for background characteristics. CONCLUSIONS: IFN was inferred to decrease tumor recurrence after treatment of HCC in patients with HBV-related cirrhosis, especially in the subgroup with high AST. PMID- 17287902 TI - Clinical features of symptomatic primary biliary cirrhosis initially complicated with esophageal varices. AB - BACKGROUND: Esophageal varices (EV), one feature of portal hypertension, have been regarded as a late complication of liver diseases. However, accumulating evidence indicates that EV sometimes develop early during the course of primary biliary cirrhosis (PBC). The prognosis is usually poorer for patients with symptomatic PBC than for those with asymptomatic PBC. Nevertheless, the clinical features and prognosis of patients with PBC whose initial symptoms are EV have not been clarified. METHODS: The clinical features and the prognosis of patients who initially developed EV without other symptoms (v-PBC) were retrospectively investigated in 54 patients with symptomatic PBC. RESULTS: The leukocyte and platelet counts were lower in patients with v-PBC than in those with PBC accompanied by other symptoms (s-PBC). Liver function tests, autoantibodies, and histological stage did not differ between patients with v-PBC and those with s PBC. Although the prognosis did not differ, the incidence of hepatocellular carcinoma was significantly higher in v-PBC than in s-PBC (P = 0.0037). CONCLUSIONS: These data indicate that v-PBC is a hypercarcinogenic state and constitutes a new subgroup of PBC. PMID- 17287901 TI - Prognostic factors for portal venous invasion in patients with hepatocellular carcinoma. AB - BACKGROUND: Factors involved in portal venous invasion (PVI) must be clarified to enable better determination of therapeutic strategies and outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Of 365 patients with HCC who consulted our department between January 1999 and January 2003, 53 with PVI at the initial consultation were excluded, and the other 312 without PVI were included in this study. Of these patients, we compared liver function, tumor markers, and initial treatment between 287 patients without PVI during follow-up (until December 2004) and 25 patients who developed PVI, and investigated prognostic factors. RESULTS: Multivariate analysis using a COX regression model showed that a Lens culinaris A-reactive fraction of alpha-fetoprotein (AFP-L3) rate of 15% or more, a des-gamma-carboxy prothrombin (DCP) level of 100 mAU/ml or more, multiple tumors, and a platelet count of 130 000/mm(3) or more were correlated with PVI. CONCLUSIONS: HCC frequently infiltrated the portal vein in patients with a high rate of AFP-L3, a high level of DCP, or multiple tumors. Furthermore, the incidence of PVI was significantly higher in patients with a platelet count of 130 000/mm(3) or more. PMID- 17287903 TI - Atypically enhanced cavernous hemangiomas of the liver: centrifugal enhancement does not preclude the diagnosis of hepatic hemangioma. AB - The imaging features of an atypically enhanced hepatic hemangioma have not been well described in the literature, and the presence of such atypia may sometimes cause clinical problems in the differential diagnosis. Herein, we report a case of hepatic hemangioma demonstrating a previously unreported atypical enhancement pattern. On dynamic computed tomography during hepatic arteriography, a centrifugal enhancement pattern and subsequent peritumoral ring-shaped enhancement mimicking corona enhancement were found in cavernous hemangiomas of the liver in a 68-year-old Japanese man. Histopathological diagnosis of cavernous hemangioma of the liver was made on a biopsy specimen. Considering the importance of differentiating benign hepatic tumor from various forms of malignancy, radiologists and hepatologists should be aware of rare enhancement patterns sometimes seen in hepatic hemangioma. Establishing knowledge of the entire spectrum of atypical hepatic hemangioma may benefit the rational approach to future cases. PMID- 17287905 TI - Transnasal ERCP/ENBD using an ultrathin esophagogastroduodenoscope. PMID- 17287904 TI - A case of deep venous thrombosis associated with pegylated interferon alpha2b plus ribavirin treatment of chronic hepatitis C. AB - We present a case of deep venous thrombosis (DVT) during pegylated interferon (peg-IFN)-alpha2b plus ribavirin treatment of chronic hepatitis C (CHC). A 67 year-old man, who had been under treatment for hypertension and diabetes mellitus, was admitted to our hospital for peg-IFN-alpha2b plus ribavirin treatment for CHC. His serum hepatitis C virus (HCV) RNA level became undetectable 1 week after the initiation of peg-IFN-alpha2b plus ribavirin treatment. He suffered from severe pain, flare, and edema in both of his lower legs 6 weeks after the initiation of peg-IFN-alpha2b plus ribavirin treatment. He was diagnosed as having DVT because of the presence of a thrombus in the right soleus vein by ultrasonography. Peg-IFN-alpha2b plus ribavirin treatment was discontinued because a causal relationship between DVT and peg-IFN-alpha2b plus ribavirin treatment was suspected. DVT was not observed and the symptoms in both of his legs were improved after the administration of warfarin potassium. Subsequently, DVT has not recurred, and he has remained HCV-RNA negative. PMID- 17287906 TI - Smoothened gene mutations found in digestive cancer have no aberrant Hedgehog signaling activity. PMID- 17287907 TI - Is it time to reconsider autoimmune pancreatitis? PMID- 17287909 TI - Analysis of polymer adsorption onto colloidal particles. AB - The structure of the layer formed after polymer adsorption onto a spherical particle is numerically studied by means of the application of the Single-Chain Mean-Field theory. We have determined several overall layer properties including the monomer volume fraction profiles, the layer thickness, adsorbances related to loops and to tails, as well as the variation of the crossover distance between loops and tails for different particle radii and fixed polymer length. When the radius of the sphere is small enough to affect the loop layer, one enters a single-adsorbed-chain regime, characterized by a critical sphere radius. In this regime, structural changes in the adsorbed layer arise. For such small sphere, the loop layer is confined to a region whose thickness is of the order of the radius of the adsorbing sphere, and two long tails dominate the outer layer and the adsorbance due to tails dominates that due to loops. An analysis of the structure of the outer tail layer for this small sphere case is also presented. PMID- 17287908 TI - Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. AB - Vitamin K mediates the synthesis of proteins regulating bone metabolism. We have tested whether high vitamin K(2) intake promotes bone mineral density and bone strength. Results showed that K(2) improved BMC and femoral neck width, but not DXA-BMD. Hence high vitamin K(2) intake may contribute to preventing postmenopausal bone loss. INTRODUCTION: Vitamin K is involved in the synthesis of several proteins in bone. The importance of K vitamins for optimal bone health has been suggested by population-based studies, but intervention studies with DXA BMD as a clinical endpoint have shown contradicting results. Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake. METHODS: A randomized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K(2) (MK-4, menatetrenone) during three years. BMC and hip geometry were assessed by DXA. Bone strength indices were calculated from DXA-BMD, femoral neck width (FNW) and hip axis length (HAL). RESULTS: K(2) did not affect the DXA-BMD, but BMC and the FNW had increased relative to placebo. In the K(2)-treated group hip bone strength remained unchanged during the 3-year intervention period, whereas in the placebo group bone strength decreased significantly. CONCLUSIONS: Vitamin K(2) helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD. PMID- 17287910 TI - The role of intraoperative cholangiogram in the management of patients recovering from acute biliary pancreatitis. AB - BACKGROUND: Use of the standard management for gallstone-associated acute pancreatitis calls for cholecystectomy with cholangiography performed during the same hospitalization after acute symptoms has decreased. No previous studies, however, have objectively addressed the usefulness of intraoperative cholangiography (IOC) for the management of this condition. This study aimed to determine the incidence of common bile duct (CBD) stones after an acute episode of gallstone pancreatitis. METHODS: The medical records of all patients who underwent a cholecystectomy and IOC after an episode of gallstone pancreatitis during the same admission between 1999 and 2004 at the University of Alberta and Royal Alexandra hospitals were examined to determine the incidence of CBD stones after resolution of gallstone pancreatitis. RESULTS: After a chart review for a series of 86 patients, 63 met the inclusion criteria. All except for one patient had undergone successful IOC (98%). Among the patients who had no evidence of CBD obstruction on preoperative imaging or lab work, three were found to have a filling defect on IOC and stones on their postoperative endoscopic retrograde cholangiopancreatography (ERCP) (3/63, 5%). This is not significantly different from the 4.6% incidence of CBD stones among patients with cholelithiasis who had normal preoperative imaging and blood work. CONCLUSION: In the setting of normal preoperative imaging and lab work, the incidence of CBD stones among patients recovering from acute mild to moderate gallstone pancreatitis is not significantly higher than among patients with no history of pancreatitis. Therefore, an IOC for post-gallstone pancreatitis does not alter management. PMID- 17287911 TI - Efficacy of percutaneous treatment of biliary tract calculi using the holmium:YAG laser. AB - BACKGROUND: Few Western studies have focused on percutaneous techniques using percutaneous transhepatic choledochoscopy (PTHC) and holmium:yttrium-aluminum garnet (YAG) laser to ablate biliary calculi in patients unable or unwilling to undergo endoscopic or surgical removal of the calculi. The authors report the efficacy of the holmium:YAG laser in clearing complex biliary calculi using percutaneous access techniques. METHODS: This study retrospectively reviewed 13 non-Asian patients with complex secondary biliary calculi treated percutaneously using holmium:YAG laser. Percutaneous access was accomplished via left, right, or bilateral hepatic ducts and upsized for passage of a 7-Fr video choledochoscope. Lithotripsy was performed under choledochoscopic vision using a holmium:YAG laser with 200- or 365-microm fibers generating 0.6 to 1.0 joules at 8 to 15 Hz. Patients underwent treatment until stone clearance was confirmed by PTHC. Downsizing and subsequent removal of percutaneous catheters completed the treatment course. RESULTS: Seven men and six women with an average age of 69 years underwent treatment. All the patients had their biliary tract stones cleared successfully. Of the 13 patients, 3 were treated solely as outpatients. The average length of percutaneous access was 108 days. At this writing, one patient still has a catheter in place. The average number of holmium:YAG laser treatments required for stone clearance was 1.6, with no patients requiring more than 3 treatments. Of the 13 patients, 8 underwent a single holmium:YAG laser treatment to clear their calculi. Prior unsuccessful attempts at endoscopic removal of the calculi had been experienced by 7 of the 13 patients. Five patients underwent percutaneous access and subsequent stone removal as their sole therapy for biliary stones. Five patients were cleared of their calculi after percutaneous laser ablation of large stones and percutaneous basket retrieval of the remaining stone fragments. There was one complication of pain requiring admission, and no deaths. CONCLUSIONS: The use of PTHC with holmium:YAG laser ablation is safe and efficacious, but requires prolonged biliary access and often multiple procedures to ensure clearance of all calculi. PMID- 17287912 TI - Postural instability does not necessarily correlate to poor performance: case in point. AB - BACKGROUND: It is very important for surgeons who perform minimally invasive surgery (MIS) to maintain proper postural stability, which kinematic research can determine. Previous studies in surgical ergonomics have shown that postural stability is correlated to instrument type, task difficulty, and skill level. What should also be considered is that surgeons may strategically change stance or joint movement to achieve better surgical outcomes while potentially subjecting themselves to greater risk. Background information about subjects, e.g., joint impairment, should be considered an important surgical ergonomic element. Such information can lead to more realistic and accurate conclusions about postural stability and joint kinematics. METHODS: A highly experienced and skilled right-handed surgeon developing carpal tunnel syndrome in both wrists was recruited into a small (6 subjects) performance study of pegboard transfer and circle-cutting tasks from the Fundamentals of Laparoscopic Surgery (FLS) skill set. Joint kinematics and postural data were collected using two associated force plates and a motion capture system of 12 digital, high-resolution, high-speed, infrared cameras. RESULTS: Each task was completed in less than 90 s. In pegboard transfer, the subject increased shoulder abduction angle to align his hand and forearm and minimize wrist flexion. When circle-cutting required excessive wrist flexion, the subject maintained his lower body position and stance while twisting his torso, a strategy that appeared to stabilize tangential direction related to cutting while maintaining a fixed orientation of forearm, wrist, and hand. In another circle-cutting trial, the subject changed his stance primarily by shifting foot position as necessary to obtain better scissor approach angles. These compensatory, strategic movements caused an increase in overall postural sway but did not represent postural instability. CONCLUSION: This case study indicated that poor joint kinematics or postural stability does not necessarily correlate to poor performance. Instead, they may indicate positive compensatory or strategic movements. PMID- 17287913 TI - Electrothermal bipolar vessel sealing device vs. ultrasonic coagulating shears in laparoscopic colectomies: a comparative study. AB - BACKGROUND: Many devices are available for vascular control during laparoscopic colorectal procedures. Ultrasonic coagulating shears (UCS), vascular staplers, titanium or plastic clips, and electrothermal bipolar vessel sealing (EBVS) are currently used according to the surgeon's preference. This study aimed to compare EBVS Ligasure with UCS. METHODS: We report the outcome of 200 consecutive unselected patients who underwent laparoscopic colorectal resections of which 100 were performed with EBVS Ligasure (from September 2004 to December 2005, group 1) and 100 with UCS harmonic scalpel (from December 2002 to June 2004, group 2). Only the following three types of operation were performed: right colectomy (RC), left colectomy (LC), and low anterior resections (LAR). Emergency procedures have been excluded. The same attending surgical teams performed or supervised all procedures. Operating time, blood loss, complications, and postoperative hospital stay were investigated. RESULTS: Age, gender, previous surgical abdominal procedures, and ASA risk were similar between the two groups, as well as was the percentage of malignant cases (74% vs. 71%, respectively). There were 32 vs. 37 RC, 50 vs. 47 LC, and 18 vs. 16 LAR in groups 1 and 2, respectively. There was no mortality in either group. A conversion to open surgery and two major complications occurred in group 2. There were no statistically significant differences in mean operating time (111 vs. 133, 140 vs. 176, and 153 vs. 201 min) and in the mean postoperative hospital stay (5.2 vs. 6.1, 6.5 vs. 7.1, and 6.8 vs 7.3 days) for RC, LC, and LAR between group 1 and 2, respectively. We do report interesting data about statistically significant differences in the blood loss: 115 vs. 370, 150 vs. 455, and 185 vs. 495 ml for RC (p < 0.001), LC (p < 0.001), and LAR (p = 0.002) between group 1 and group 2, respectively. CONCLUSIONS: In our laparoscopic colorectal experience, EBVS Ligasure has proven safe and effective in vessel sealing. Patients in whom this device was used had less blood loss and slight advantages in operating time and postoperative hospital stay. PMID- 17287914 TI - Fixity of ports to the abdominal wall during laparoscopic surgery: a randomized comparison of cutting versus blunt trocars. AB - BACKGROUND: Dislodgement of ports from the abdominal wall is a common problem during laparoscopic surgery. The aim of this study was to evaluate port stability using either cutting or blunt-tipped trocars. METHODS: Patients undergoing laparoscopic surgery were randomized to have the secondary ports inserted using either cutting or blunt-tipped trocars. The fixity of ports to the abdominal wall was evaluated at the start and completion of surgery by measuring the total traction force required to displace the ports. Similarly, the friction forces required to displace instruments within the ports were measured. RESULTS: Thirty patients were randomized into two groups (15 patients in each group), and a total of 114 ports (cutting, n = 51; blunt, n = 63) were evaluated. The groups were comparable in age, gender, body mass index, and operating time. The total traction forces needed to displace the 5-mm and 10-mm ports were significantly lower when cutting trocars were used at both the beginning (2.6 vs. 11.8 N, p < 0.001, and 6.3 vs. 15.5 N, p = 0.014, respectively) and completion of surgery (1.3 vs. 6.7 N, p < 0.001, and 1.1 vs. 12.0 N, p = 0.001, respectively). The declines in the total traction forces from the start to the completion of surgery were significant for the 5-mm and 10-mm cutting-trocar ports (p = 0.031 and p = 0.043, respectively) but not for the blunt-trocar ports (p = 0.088 and p = 0.152, respectively). While no significant differences between the instruments' friction forces and the traction forces of the cutting-trocar ports were observed, the former were significantly lower than the traction force needed to displace the blunt-trocar ports. This explains the significantly greater frequency of spontaneous port dislodgements when cutting ports were employed (25.5% vs. 1.6%, p < 0.001). Port-site bleeding was encountered only in patients (n = 2, 13%) where cutting trocars were used. CONCLUSIONS: Port fixity to the abdominal wall during laparoscopic surgery declines with time. The insertion of ports using a blunt-tipped trocar is associated with significantly greater stability and fixity of the port to the abdominal wall. The use of blunt-tipped trocars is recommended for routine practice in laparoscopic surgery. PMID- 17287915 TI - A research agenda for gastrointestinal and endoscopic surgery. AB - BACKGROUND: Development of a research agenda may help to inform researchers and research-granting agencies about the key research gaps in an area of research and clinical care. The authors sought to develop a list of research questions for which further research was likely to have a major impact on clinical care in the area of gastrointestinal and endoscopic surgery. METHODS: A formal group process was used to conduct an iterative, anonymous Web-based survey of an expert panel including the general membership of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). In round 1, research questions were solicited, which were categorized, collapsed, and rewritten in a common format. In round 2, the expert panel rated all the questions using a priority scale ranging from 1 (lowest) to 5 (highest). In round 3, the panel re-rated the 40 questions with the highest mean priority score in round 2. RESULTS: A total of 241 respondents to round 1 submitted 382 questions, which were reduced by a review panel to 106 unique questions encompassing 33 topics in gastrointestinal and endoscopic surgery. In the two successive rounds, respectively, 397 and 385 respondents ranked the questions by priority, then re-ranked the 40 questions with the highest mean priority score. High-priority questions related to antireflux surgery, the oncologic and immune effects of minimally invasive surgery, and morbid obesity. The question with the highest mean priority ranking was: "What is the best treatment (antireflux surgery, endoluminal therapy, or medication) for GERD?" The second highest-ranked question was: "Does minimally invasive surgery improve oncologic outcomes as compared with open surgery?" Other questions covered a broad range of research areas including clinical research, basic science research, education and evaluation, outcomes measurement, and health technology assessment. CONCLUSIONS: An iterative, anonymous group survey process was used to develop a research agenda for gastrointestinal and endoscopic surgery consisting of the 40 most important research questions in the field. This research agenda can be used by researchers and research-granting agencies to focus research activity in the areas most likely to have an impact on clinical care, and to appraise the relevance of scientific contributions. PMID- 17287916 TI - Effect of robotic assistance on the "learning curve" for laparoscopic hand assisted donor nephrectomy. AB - BACKGROUND: The number of living-related donor kidney transplantations have increased since the advent of minimally invasive surgery. Robotic technology has emerged as a promising alternative to laparoscopic techniques. The authors reviewed their institution experience with robotic hand-assisted donor nephrectomies (RHADNs). METHODS: Between August 2000 and April 2006, 273 robotically assisted left donor nephrectomies were performed using a hand assisted technique. Prospectively collected information for 214 patients regarding complications, hospital stay, blood loss, warm ischemia time, operative time, and outcomes is presented. RESULTS: The cohort of donors included 110 men and 104 women with a mean age of 36 years (range, 18-61 years). These donors included 86 African Americans, 46 Caucasians, 74 Hispanics, and 8 of other races. Left renal artery anomalies were found in 61 patients (29%). Four patients underwent conversion to open surgery. The hospital stay was 2.3 days (range, 1-8 days), the blood loss 82 ml (range, 10-1,500 ml), and the mean warm ischemia time 98 s (range, 50-200 s). The operative time was 201 min (range, 100-320 min) for the first 74 cases, 129 min (range, 65-240 min) for the second 70 cases, and 103 min for the last 70 cases (p < 0.001), for an overall average of 150 min. Complications decreased significantly after the first 74 cases. The 1-year patient survival rate was 100%, and the 1-year graft survival rate was 98%. The average recipient creatinine at 6 months was 1.4 mg/dl. CONCLUSIONS: Specific changes in operative technique over time have improved patient safety and diminished complications with RHADN. Currently, RHADN can be performed expeditiously with a minimal rate of complications and conversion to open procedure by a surgical team with appropriate training and experience. PMID- 17287917 TI - Perioperative outcome after laparoscopic radiofrequency ablation of liver tumors: an analysis of 521 cases. AB - BACKGROUND: Radiofrequency thermal ablation (RFA) is gaining increased acceptance for the treatment of unresectable primary and metastatic liver tumors. Understanding the morbidity and laboratory changes after RFA is important for operative indications and perioperative management. METHODS: The authors prospectively analyzed the 30-day morbidity and mortality rates of patients undergoing laparoscopic RFA for liver tumors in a 10-year period. Laboratory studies included a complete blood count, electrolytes, liver function tests, prothrombin time/international normalized ratio (INR), and tumor markers obtained preoperatively, on postoperative days (PODs) 1 and 7, then at 3 months. RESULTS: A total of 521 RFA procedures were performed for 428 patients (286 men and 142 women) with a mean age of 61 years (range, 25-89 years). A total of 346 patients underwent a single operation, and 82 patients had two or more operations. The pathology was metastatic colon cancer for 244 patients (47%), hepatocellular cancer for 109 patients (21%), metastatic neuroendocrine cancer for 74 patients (14%), and other noncolorectal, nonneuroendocrine liver metastasis for 94 patients (18%). A total of 1,636 lesions (mean, 3.1 per patient; range, 1-16) were ablated. The mean tumor size was 2.7 +/- 1.6 cm (range, 0.3-11.5 cm). All cases were managed laparoscopically. The 30-day mortality rate was 0.4% (n = 2), and the morbidity rate was 3.8 % (n = 20). The average length of hospital stay was 1 day for RFA-only cases and 2.1 days when another surgical procedure was combined with RFA. Serum aspartate aminotransferase (AST) increased 14-fold, alanine aminotransferase (ALT) increased 10-fold, and bilirubin levels increased 2-fold on POD 1, with return to baseline in 3 months. Serum alkaline phosphatase and gamma-glutamyltransferase (GGT) levels showed a 25% increase on POD 7, with return to baseline in 3 months. There were no significant changes in platelet counts or prothrombin times postoperatively. CONCLUSIONS: This large series provides valuable insight into the perioperative period and allows the expected morbidity of the procedure to be understood. Despite significant patient comorbidities, this procedure was tolerated with low morbidity and mortality rates. Postoperative coagulopathy was not observed. A postoperative rise in liver function tests is expected, reflecting the liver injury response to RFA. This information can be used to expand the patient population that may benefit from laparoscopic RFA. PMID- 17287919 TI - Complications of laparoscopic radical hysterectomy and lymphadenectomy for invasive cervical cancer: experience based on 317 procedures. AB - BACKGROUND: This report presents the incidence of complications and conversions during laparoscopic radical hysterectomy and lymphadenectomy performed for invasive cervical carcinoma. The data are analyzed, and strategies to help prevent future complications are discussed. METHODS: From July 2000 to December 2005 at the authors' institution, 317 laparoscopic radical hysterectomy and lymphadenectomy procedures for invasive cervical carcinoma were performed. The authors reviewed the database of patients who underwent laparoscopic radical hysterectomy and lymphadenectomy to examine complications and analyze factors associated with conversion to an open surgical procedure. RESULTS: All but four surgical procedures were laparoscopically completed. Pelvic lymphadenectomy was performed for all the remaining 313 patients, 143 of whom underwent paraaortic lymphadenectomy. Major and minor intraoperative complications occurred for 4.4% (n = 14) of the patients. The overall conversion rate was 1.3% (n = 4), including 3 emergencies and 1 elective conversion. Seven patients had vessel injuries, five of which were repaired or treated laparoscopically. One left external iliac vein required laparotomy, and one patient underwent laparotomy to control bleeding sites. Operative cystotomies occurred in five patients, which were repaired laparoscopically. Two patients underwent laparotomy because of hypercapnia and ascending colon injury. Postoperative surgery complications occurred in 5.1% (n = 16) of the patients, including 5 patients with ureterovaginal fistula, 4 with vesicovaginal fistula requiring reoperation, 1 with ureterostenosis treated by placement of a double-J ureteral stent, and 6 with bladder dysfunctions (retention) that exhibited complete resolution within 3 to 6 months by intermittent training and catheterization. CONCLUSIONS: Laparoscopic radical hysterectomy and lymphadenectomy is becoming a routine procedure in the armamentarium of many gynecologists. Complications unique to laparoscopy do exist, but they decrease with repeated training of the procedure and gradually enriched experiences. PMID- 17287918 TI - Telerobotic gastrointestinal surgery: phase 2--safety and efficacy. AB - BACKGROUND: The Federal Drug Administration (FDA) approved the da Vinci surgical system for all abdominal operations in July 2000. In the past 6 years, virtually all gastrointestinal operations have been accomplished using telerobotic techniques. The purpose of this review is to summarize the short-term outcomes achieved with telerobotic gastrointestinal operations. METHODS: All case series of telerobotic gastrointestinal operations identified by PubMed searches are included in this review. RESULTS: Case series document the safety and efficacy of telerobotic cholecystectomy, fundoplication, Heller myotomy, gastric bypass, colectomy, gastrectomy, and pancreatectomy. The procedures were accomplished with low rates of conversion to laparoscopic operations, mortality, and morbidity. When comparison groups were available, the analysis shows that telerobotic operations required more time than the laparoscopic operations, although for telerobotic cholecystectomy and telerobotic fundoplication, this difference disappeared in 10 to 20 operations. Specific patient advantages were not identified for telerobotic operations compared with laparoscopic operations, except for a decreased esophageal perforation rate during telerobotic Heller myotomy. Surgeons benefited from the three-dimensional imaging, the handlike motions of the robotic instruments, and an ergonomically comfortable position. CONCLUSION: All telerobotic gastrointestinal operations are feasible and can be performed with safety and efficacy. It is difficult to demonstrate patient specific advantages of telerobotic surgery over laparoscopic operations. Nonetheless, telerobotic surgical systems offer distinct advantages to surgeons and may facilitate an increase in the number of surgeons performing advanced laparoscopic gastrointestinal operations. In addition, telerobotics offer a digital information platform that enables surgical simulation and augmented reality surgery. PMID- 17287920 TI - Evaluation of acellular human dermis reinforcement of the crural closure in patients with difficult hiatal hernias. AB - BACKGROUND: Biologic prosthetics may circumvent mesh-related complications at the esophageal hiatus by becoming remodeled by native cells. We present our experience with acellular human dermal matrix in the repair of difficult hiatal hernias (HH). METHODS: Records of 17 patients who underwent laparoscopic HH repair using acellular human dermis to buttress the crural closure were analyzed. Hernias were paraesophageal (PEH) in 12 patients, large type 1 in 1 patient, and recurrent after prior HH repair in 4 patients. Barium swallow (BAS) was obtained 6-12 months after surgery. (Data are presented as mean +/- standard deviation.) RESULTS: Mean patient age was 65 +/- 12 years and BMI was 31 +/- 4. Mean gastroesophageal (GE) junction distance above the diaphragm in the PEHs was 4.9 +/- 1.5 cm; 9 of 12 patients with PEH had more than 50% of the stomach in the chest. Mean operating time was 273 +/- 48 min. Average hiatal defect size was 4.7 x 2.7 cm, with 4.2 +/- 1.2 sutures used to close the crura. Nissen fundoplication was performed in all patients, esophageal lengthening in four patients, and anterior gastropexy in three patients. Mean hospital length of stay (LOS) was 2.3 +/- 0.8 days. Mean followup was 14.4 +/- 4.4 months. Postoperatively, only one (6%) patient had heartburn/regurgitation, one (6%) had mild dysphagia, and two (12%) take proton pump inhibitors. Followup BAS at 10.3 +/- 4.9 months after surgery showed small recurrent hernias in two patients (12%), but only one was symptomatic. In addition, there was one symptomatic failure of a redo Nissen in an obese patient. Reoperative gastric bypass 15 months later showed an intact crural closure with a remodeled buttress site. CONCLUSIONS: Acellular human dermal matrix may be an effective method to buttress the crural closure in patients with large hiatal hernias. Longer followup in larger numbers of patients is needed to assess the validity of this approach. PMID- 17287921 TI - Expression of ectonucleotide pyrophosphate phosphodiesterase and peroxisome proliferator activated receptor gamma in morbidly obese patients. AB - BACKGROUND: Recently, two genes, peroxisome proliferator activated receptor gamma (PPARgamma) and ectonucleotide pyrophosphate phosphodiesterase (ENPP1), have been localized and associated with diabetes and obesity. This report hypothesizes that there is a correlation between the genetic expression of ENPP1 and PPARgamma from gastrointestinal tissue and body mass index (BMI). METHODS: Preoperative demographic data were collected from 16 severely morbidly obese patients. Extraneous gastrointestinal tissue was obtained during laparoscopic gastric bypass and gastric banding procedures. The tissue was snap frozen in liquid nitrogen. Initially, RNA extraction was performed on the tissue, followed by reverse transcription using appropriate primers and controls. Subsequently, the samples were subjected to quantitative polymerase chain reaction (PCR). Preoperative demographic data were analyzed for their influence on ENPP1 and PPARgamma expression using multivariate analysis and logistic regression models. RESULTS: Expression of PPARgamma and ENPP1 was found in all samples. There was a higher level of PPARgamma expression in omental tissue than in enteric tissue. There was no significant difference in the expression of ENPP1 among the different tissue types. The relative level of PPARgamma expression in small bowel and gastric tissue was found to be inversely proportional to body mass index (BMI) using linear regression analysis (p = 0.01; r (2) = 0.586). Similarly, PPARgamma expression from omental tissue showed an inverse relationship with BMI (p = 0.04; r (2 )= 0.576). The levels of ENPP1 expression did not show a correlation with BMI (p = 0.25). CONCLUSION: The results suggest that increasing obesity correlates with a decrease in PPARgamma expression. This decrease may induce dysfunctional adipocyte differentiation, maturation, and function, leading to diabetes and the metabolic syndrome. Similarly, the increased volume of adipose tissue may lead to a downregulation of PPARgamma. The lack of correlation between ENPP1 and BMI may suggest that glucose metabolism is more complex than lipid metabolism. Further evaluation is warranted to establish metabolic pathways for glucose and lipid biomarkers. PMID- 17287922 TI - Italian multicentric survey on laparoscopic spleen surgery in the pediatric population. AB - BACKGROUND: Some technical aspects of laparoscopic spleen surgery still are debated, although efforts have been made to standardize them. The position of the patient, the approach to the spleen, vessel identification and division, and spleen extraction can vary from center to center. METHODS: This retrospective muticentric study led by the Societa Italiana di Videochirurgia Infantile (SIVI) examined indications, surgical details, and complications of laparoscopic spleen surgery in the pediatric population during a 5-year period. RESULTS: The study period from January 1999 to December 2003 (5 years) involved nine centers and included 85 patients with a mean age of 10 years (range, 2-17 years). Hypersplenism or severe hemolysis in cases of hematologic disorders represented the most important indications. More than 90% of the patients underwent total laparoscopic splenectomy. Specific technical details from each center were collected. Intraoperative complications occurred in 19% of the patients (hemorrhage in 8% and technical problems in 14%), and 6% of the patients required conversion to the open approach. No deaths occurred, and no reoperations were required. Postoperative complications were experienced by 2% of the patients. CONCLUSION: Laparoscopic spleen surgery is safe, reliable, and effective in the pediatric population. On the basis of the results, some technical details for laparoscopic spleen surgery can be suggested. The patient is preferably kept supine or lateral, approaching the spleen anteriorly. Moreover, the ilar vessels should be identified selectively and individually, with initial artery division performed to achieve spleen shrinking. Any hemostatic device proved to be effective in experienced hands. Once freed, the spleen is preferably extracted via a suprapubic cosmetic transverse incision (faster, easier, and safer), although a bag can be used. Finally, the size of the spleen does not represent a contraindication for a trained and experienced surgeon. Nevertheless, this parameter must be considered when laparoscopic spleen surgery is planned. PMID- 17287924 TI - Thickened fluids and water absorption in rats and humans. AB - Individuals with dysphagia are commonly provided with oral fluids thickened to prevent aspiration. Most thickening agents are either gum-based (guar or xanthan) or are derived from modified starches. There is evidence, predominantly anecdotal, that dysphagic individuals are subclinically dehydrated. Dysphagia has a particular impact on elderly individuals and there is justifiable concern for dehydration in this population. It has been speculated that dehydration may, in part, be the result of the water-holding capacity of these thickening agents decreasing water absorption from the gut. The aim of this study was to determine the rate of intestinal absorption of water from thickened fluids. The method used was a laboratory tracer study in rats and humans in vivo. We found that there were no significant differences in water absorption rates between thickened fluids or pure water irrespective of thickener type (modified maize starch, guar gum, or xanthan gum). These data provide no support for the view that the addition of thickening agents, irrespective of type, to orally ingested fluids significantly alters the absorption rate of water from the gut. PMID- 17287925 TI - Management of dysphagia in toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). AB - Toxic epidermal necrolysis (TEN) is a rare and potentially fatal skin disorder, precipitated by severe allergic drug reaction, and is one of a spectrum of conditions, which includes Stevens-Johnson syndrome (SJS). Mucosal involvement is common, resulting in extreme pain on swallowing and poor oral intake. The aim of this study was to describe swallow function in TEN and SJS and define the role of Speech Pathology in management. The Burns Unit database was reviewed for patients that presented over a five-year period with TEN and SJS. Diagnosis of TEN and SJS was confirmed by skin biopsy. Information specific to swallow function, treatment approaches, and adequacy of oral intake was collected. Fourteen patients' medical records were studied: eight TEN, two TEN/SJS spectrum, and four SJS. The majority had mucosal involvement causing odynophagia, poor oral intake, an ability to tolerate fluids more easily than solids, and increased aspiration risk. These symptoms were confirmed by Speech Pathology swallowing assessment. Severe mucosal involvement resulting in odynophagia, dysphagia, and poor oral intake is common in TEN and SJS. The speech pathologist is able to assess swallow function and provide recommendations to promote safe oral intake, minimize odynophagia, and facilitate nutritional input critical to optimizing recovery. PMID- 17287923 TI - Laparoscopic incisional hernia repair: are transfascial sutures necessary? A review of the literature. AB - BACKGROUND: Laparoscopic repair of incisional and ventral hernias is rapidly becoming more commonplace in the armamentarium of general surgeons. Its utility and low recurrence rates make it a very attractive option. As with all newer procedures, controversies exist with this approach. One significant aspect is the method of fixation for the biomaterial. Most authors add the use of transfascial sutures. Others, in the minority, do not. METHODS: A literature search using Medline and PubMed was used to evaluate the best practice for fixation in laparoscopic incisional and ventral hernia repair. RESULTS: This review of the current literature (including comparative series) seems to show that the recurrence rate is approximately 4% with the use of sutures and 1.8% without their use. However, these data do not show that there is tremendous variation in the method and manner of placing transfascial sutures or that long-term follow-up evaluation is inadequate in most series. No firm conclusions can be drawn about whether it is detrimental to omit the use of transfascial sutures. CONCLUSIONS: On the basis of this review, a larger overlap of the prosthesis (5 vs 3 cm) is necessary if sutures are not used. If sutures are used, they should be placed no more than 5 cm apart. Prospective randomized trials with and without of transfascial sutures using a consistent biomaterial are necessary to settle this issue. PMID- 17287926 TI - Hyoid bone and laryngeal movement dependent upon presence of a tracheotomy tube. AB - The aim of this prospective, consecutive study was to investigate the biomechanical effects, if any, of the presence of a tracheotomy tube and tube cuff status, tube capping status, and aspiration status on movement of the hyoid bone and larynx during normal swallowing. Seven adult patients (5 male, 2 female) with an age range of 46-82 years (mean = 63 years) participated. Criteria for inclusion were no history of cancer of or surgery to the head and neck (except tracheotomy), normal cognition, normal swallowing, and ability to tolerate decannulation. Digital videofluoroscopic swallowing studies were performed at 30 frames/s and with each patient seated upright in the lateral plane. Variables evaluated included maximum hyoid bone displacement and larynx-to-hyoid bone approximation under three randomized conditions: tracheotomy tube in and open with a 5-cc air-inflated cuff; tracheotomy tube in and capped with deflated cuff; and tracheotomy tube out (decannulated). Differences between maximum hyoid bone displacement and larynx-to-hyoid approximation (cm) based on presence/absence of a tracheotomy tube, tube cuff status, and tube capping status were analyzed with the Student's t test. Reliability testing with a Pearson product moment correlation was performed on 21% of the data. No significant differences (p > 0.05) were found for both maximum hyoid bone displacement and larynx-to-hyoid bone approximation during normal swallowing based on tracheotomy tube presence, tube cuff status, or tube capping status. Intraobserver reliability for combined measurements of maximum hyoid displacement and larynx-to-hyoid approximation was r = 0.97 and interobserver reliability for the absence of aspiration was 100%. For the first time with objective data it was shown that the presence of a tracheotomy tube did not significantly alter two important components of normal pharyngeal swallow biomechanics, i.e., hyoid bone movement and laryngeal excursion. The hypothesis that a tracheotomy tube tethers the larynx thereby preventing hyoid bone and laryngeal movement during normal swallowing is not supported. PMID- 17287927 TI - Are behavioral problems in childhood and adolescence associated with bipolar disorder in early adulthood? AB - Several recent studies have found an association between conduct problems and bipolar disorder in adolescents. However, prospective studies are rare and most do not apply multivariable analysis strategies to control for important variables (e.g. socio-demographics). The aim of this study was to test the association between certain conduct problems and bipolar disorders. The sample consisted of 591 adolescents (male and female) representative for 2,600 persons from the Canton of Zurich in Switzerland. Data were prospectively collected through an interviewing procedure, with the first screening taking place at the age of 19 20. The incidence rate was computed using sampling weights, and risk factors of bipolar II disorder were estimated using a multivariable logistic regression model. The 9-year incidence rate of bipolar II disorder in the canton of Zurich was 8.4% (n = 65). Adolescents and children showing behavior such as repeated running away from home and physical fighting were 2.6-3.5 times more likely to experience a bipolar II disorder than those with no indication of conduct problems. Sensitivity analysis showed that the conduct problems were not the result of low socio-economic status. PMID- 17287929 TI - A novel microfluidic flow-injection analysis device with fluorescence detection for cation sensing. Application to potassium. AB - A microfabricated device has been developed for fluorimetric detection of potassium ions without previous separation. It is based on use of a fluorescent molecular sensor, calix-bodipy, specially designed to be sensitive to and selective for the target ion. The device is essentially made of a Y-shape microchannel moulded in PDMS fixed on a glass substrate. A passive mixer is used for mixing the reactant and the analyte. The optical detection arrangement uses two optical fibres, one for excitation by a light-emitting diode, the other for collection of the fluorescence. This system enabled the flow-injection analysis of the concentration of potassium ions in aqueous solutions with a detection limit of 0.5 mmol L(-1) and without interference with sodium ions. A calibration plot was constructed using potassium standard solutions in the range 0-16 mmol L( 1), and was used for the determination of the potassium content of a pharmaceutical pill. Figure Photography of the microfluidic channel showing the ridges in the PDMS substrate at the top of the channel. PMID- 17287930 TI - Development and application of an ultratrace method for speciation of organotin compounds in cryogenically archived and homogenized biological materials. AB - An accurate, ultra-sensitive and robust method for speciation of mono, di, and tributyltin (MBT, DBT, and TBT) by speciated isotope-dilution gas chromatography inductively coupled plasma-mass spectrometry (SID-GC-ICPMS) has been developed for quantification of butyltin concentrations in cryogenic biological materials maintained in an uninterrupted cryo-chain from storage conditions through homogenization and bottling. The method significantly reduces the detection limits, to the low pg g(-1) level (as Sn), and was validated by using the European reference material (ERM) CE477, mussel tissue, produced by the Institute for Reference Materials and Measurements. It was applied to three different cryogenic biological materials-a fresh-frozen mussel tissue (SRM 1974b) together with complex materials, a protein-rich material (whale liver control material, QC03LH03), and a lipid-rich material (whale blubber, SRM 1945) containing up to 72% lipids. The commutability between frozen and freeze-dried materials with regard to spike equilibration/interaction, extraction efficiency, and the absence of detectable transformations was carefully investigated by applying complementary methods and by varying extraction conditions and spiking strategies. The inter-method results enabled assignment of reference concentrations of butyltins in cryogenic SRMs and control materials for the first time. The reference concentrations of MBT, DBT, and TBT in SRM 1974b were 0.92 +/ 0.06, 2.7 +/- 0.4, and 6.58 +/- 0.19 ng g(-1) as Sn (wet-mass), respectively; in SRM 1945 they were 0.38 +/- 0.06, 1.19 +/- 0.26, and 3.55 +/- 0.44 ng g(-1), respectively, as Sn (wet-mass). In QC03LH03, DBT and TBT concentrations were 30.0 +/- 2.7 and 2.26 +/- 0.38 ng g(-1) as Sn (wet-mass). The concentration range of butyltins in these materials is one to three orders of magnitude lower than in ERM CE477. This study demonstrated that cryogenically processed and stored biological materials are a promising alternative to conventional freeze-dried materials for organotin speciation analysis, because these are, at present, the best conditions for minimizing degradation of thermolabile species and for long term archival. Finally, the potential of the analytical method was illustrated by analysis of polar bear (Ursus maritimus) and beluga whale (Delphinapterus leuca) liver samples that had been collected in the Arctic and archived at the Marine Environmental Specimen Bank. Significant concentrations of butyltin compounds were found in the samples and provide the first evidence of the presence of this class of contaminant in the Arctic marine ecosystem. Figure Eye catch image. PMID- 17287931 TI - [On the centennial of Ernst von Bergmann's death]. AB - "dear aunt lina. i do not know any big letters yet, but i want to thank you in small letters for the beautiful pens. say hello to grandpa and to everybody. yours truly, ernst." These are the first surviving written words of Ernst von Bergmann. Between them and his last words about his suspected colon cancer on 25 March 1907 ("I diagnosed this 5 years ago, and now it has come to pass.") lie many years in a vigorous life characterised by untiring activity and creativity, self-discipline, and care for patients and his family. They were years of enormous success in surgery and private happiness but also of professional setbacks and tragic family loss. Ernst von Bergmann became a leading German surgeon not only because of his surgical and scientific achievements, particularly in the fields of asepsis and war surgery, but also due to his exemplary character, reliability, engaging personality, and commitment to medical training in various medical societies. Of these, the German Society of Surgery is most indebted to him. After assuming a chair in surgery in 1882, he continued to play a leading role in this society, not least as its five-time president from 1888 to 1890 and in 1896 and 1900. A worthy successor to Bernhard von Langenbeck, he was a full professor at the Berlin University Hospital for 25 years. He also taught at the Medical and Surgical Academy for the Military after being appointed there by Emperor Wilhelm I on 16 November 1882. This position was important to him and corresponded to his patriotic views. PMID- 17287932 TI - The probiotic Escherichia coli strain Nissle 1917 (EcN) stops acute diarrhoea in infants and toddlers. AB - In most cases, acute diarrhoea will become self-limiting during the first few days after onset. For young children, however, health risks may develop when the disease lasts longer than 3 days. The purpose of the present trial was to determine whether the stool frequency of infants and toddlers suffering from acute diarrhoea could be normalised more quickly by administering the probiotic Escherichia coli Nissle 1917 (EcN) solution than by administering a placebo. The safety of EcN were also assessed. A total of 113 children (aged 2-47 months) with acute diarrhoea (> three watery or loose stools in 24 h) were randomised to either a group receiving the probiotic EcN suspension (n = 55) or a group receiving the placebo suspension (n = 58) in a confirmative, double-blind clinical trial. Depending on the age of patients, 1-3 ml per day of verum suspension (10(8) viable EcN cells per millilitre) or placebo were administered orally. The causes of the diarrhoea were viral rather than bacterial, but they were mainly unspecific infections. The median onset of treatment response (reduction of daily stool frequency to 0.05). Administration of ICKT in postoperative BA patients appears to lower the serum levels of markers of fibrosis in the medium term. Whether this in fact correlates with prevention cannot be determined from this paper, but ICKT would appear to protect against liver fibrosis. Long-term studies are required to determine the exact role ICKT plays in prognosis of BA patients. PMID- 17287943 TI - Treves' field congenital hernias in children: an unsuspected rare cause of acute small bowel obstruction. AB - The Treves' field congenital hernias (TFCH) are an unusual cause of bowel obstruction that may result in irreversible damage of the small bowel or a fatal outcome, unless treated timely and properly. We analyzed retrospectively the medical records of four patients who underwent surgery for TFCHs over a period of 9 years. The types of TFCHs, only diagnosed at surgery, were identified as transmesenteric through a defect in Treves' field in three patients, and as hernia into Treves' field pouch in one patient. Patients had non-specific clinical manifestations, and imaging findings demonstrated only small bowel obstruction. Delay in accurate preoperative diagnosis, and especially patient related delay, led to a primary enterectomy-anastomosis for necrotic small bowel in the patients with transmesenteric hernias. One infant with necrotic bowel died postoperatively. It may be difficult to diagnose TFCHs in children preoperatively. Misdiagnosis of bowel obstruction caused by this type of internal hernia might lead to small bowel necrosis or death. The risk of this complication seems to be more influenced by pre-hospital delay. Awareness of the severe consequences of delay in diagnosis, high clinical suspicion, early recognition, and proper surgical intervention are essential in the successful management of TFCHs. PMID- 17287945 TI - Imatinib-induced Stevens-Johnson syndrome: recurrence after re-challenge with a lower dose. PMID- 17287944 TI - Incidence and management of the inguinal hernia during laparoscopic orchiopexy in palpable cryptoorchidism: preliminary report. AB - During the laparoscopic approach of undescended testis, an associated inguinal hernia is a frequent finding that must be treated at the same time. The objective of this presentation is to show the incidence and management of the inguinal hernia that were found during laparoscopic orchidopexy, reporting how the scar tissue will join the edges of the canal and the parietal peritoneum will grow above. Between January 1999 and December 2002, 31 patients with 33 palpable and nonpalpable undescended testes were treated by laparoscopic orchidopexy. Patients were between 6 months and 9 years. We used four ports, and 2 mm instrument. When an associated inguinal hernia were found we only removed the membranes of the processus vaginalis and did not close the defect. All cases were treated by the same surgeon. The average surgical time was 50 min that included the orchiopexy and the treatment of the associated inguinal hernia. We found inguinal hernia in 23 cases (69.9%). We did not find any inguinal hernia in the opposite side of the undescended testis. In two patients with bilateral undescended testis that were approached in two stages 3 months later we confirmed the closure of the hernia defect. These 23 patients have 21.5 months average follow up and confirm no recurrence. With an average follow up of 21.5 months, we found no inguinal hernia in any of the patients. A larger volume study with longer follow up is needed to confirm that there is no need for closure of the internal inguinal ring during laparoscopic orchidopexy. PMID- 17287946 TI - [Quantification of coronary artery stenoses: comparison of 64-slice and dual source CT angiography with cardiac catheterization]. AB - BACKGROUND: Until now stenoses of the coronary arteries have been evaluated visually with CT angiography. Therefore, the results were highly dependent on subjective factors inherent in the examiner. New software tools for semiquantitative analysis (CT-QCA, quantitative coronary assessment) might be adequate to improve the diagnostic accuracy und reproducibility. MATERIAL AND METHODS: CTAs of 20 patients were analyzed. Ten patients each were evaluated using 64-slice CT (64SCT) and dual source CT (DSCT) (Somatom Sensation 64 and Somatom Definition, Siemens Medical Solutions, Forchheim), respectively. Two radiologists independently evaluated the data visually and with the help of a software tool (Syngo Circulation, Siemens Medical Solutions, Forchheim). The results of the quantitative assessment of the invasive heart catheterization served as the reference standard. Sensitivity and specificity as well as the correlation coefficient, the systematic error, and the interobserver agreement (kappa) were determined. RESULTS: In each of both patient groups 12 stenoses were detected. For the detection of stenoses >75%, sensitivity and specificity for the visual evaluation using the 64SCT were 100% and 90%, and with the CT-QCA both were 100%. For the DSCT sensitivity and specificity were 100% for both the visual and semiautomated evaluation. The Bland-Altman plot of the results of the 64SCT showed an overestimation of 3.3% (+/-62.7%/56.2%) compared to the heart catheterization. The results of the DSCT exhibited an overestimation of 6.2% (+/ 33.1%/19.8%). The interobserver agreement of the CT-QCA and the visual evaluation showed a kappa value of 0.75 and for DSCT of 1.0. CONCLUSION: The results showed a good correlation of grading stenosis between the software-assisted evaluation and the results of the coronary catheter angiography. The promising results of the DSCT are due to a superior temporal resolution compared to the 64SCT. Confirmation of these data by trials in larger patient collectives is warranted. PMID- 17287948 TI - SP110 polymorphisms are not associated with pulmonary tuberculosis in a South African population. AB - Susceptibility to tuberculosis (TB) in mice has recently been attributed to the Ipr1 gene. Polymorphisms in the human homologue, SP110, have been investigated in various populations with only one study finding an association with TB susceptibility. We investigated eight SP110 polymorphisms in a South African population, including two novel polymorphisms. No significant association was found with any of the polymorphisms investigated, including two polymorphisms that were previously found to be associated with TB susceptibility in West African populations. PMID- 17287947 TI - Upregulation of leptin pathway correlates with abnormal expression of SERCA2a, phospholamban and the endothelin pathway in heart failure and reversal by CPU86017. AB - Emerging evidence indicates that leptin may be a potential new target in chronic heart failure (CHF) treatment. We hypothesized that hyperleptinemia may correlate with abnormal expression of SERCA2a, PLB (phospholamban), and the endothelin (ET) pathway in CHF. An activated ET pathway is involved in CHF that is suppressed by CPU86017 (p-chlorobenzyltetrahydroberberine chloride), a complex class III antiarrhythmic agent with an antioxidant effect. Thus, relief of CHF may be mediated by a reversal of abnormalities of the leptin system, the ET-reactive oxygen species (ROS) pathway, SERCA2a, and PLB by CPU86017. CHF was produced by coronary artery ligation for 6 weeks in rats. The rats were divided into 3 groups: sham, CHF untreated, and CHF+CPU86017 (4 mg/kg per day, s.c.). Hemodynamic changes, cardiac morphology, serum biochemistry, messenger ribonucleic acid (mRNA) and protein expression of the leptin pathway, ET pathway, and redox were measured. In CHF rats, hemodynamic abnormalities, cardiac remodeling, and histological changes with features of cardiac failure were associated with hyperlipidemia accompanied by oxidative stress and upregulated OB Rb, ECE, pp-ET-1, ET(A)R, and ET(B)R mRNA expression in the myocardium. Protein expression of leptin and ET(A)R in the myocardium was markedly increased in CHF rats. An activated leptin pathway was associated with downregulation of SERCA2a and upregulation of PLB in mRNA and protein expression in CHF. CPU86017 downregulated the leptin system and reversed the above changes in the myocardium. An activated leptin pathway correlates with abnormal expression of SERCA2a and PLB and an activated ET-ROS system in the affected myocardium. The multi-ion channel-blocking and antioxidative effects of CPU86017 downregulate the leptin pathway and ET system, resulting in reversal of the abnormalities of expression of SERCA2a and PLB and cardiac performance in CHF. PMID- 17287949 TI - Systematic screening of lysyl oxidase-like (LOXL) family genes demonstrates that LOXL2 is a susceptibility gene to intracranial aneurysms. AB - Four lysyl oxidase family genes (LOXL1, LOXL2, LOXL3, and LOXL4), which catalyze cross-linking of collagen and elastin, were considered to be functional candidates for intracranial aneurysms (IA) and were extensively screened for genetic susceptibility in Japanese IA patients. Total RNA was isolated from four paired ruptured IA and superficial temporal artery (STA) tissue and examined by real-time RT-PCR. The expression of LOXL2 in the paired IA and STA tissues was elevated in the IA tissue. A total of 55 single nucleotide polymorphisms (SNPs) of LOXL1-4 were genotyped for an allelic association study in 402 Japanese IA patients and 462 Japanese non-IA controls. Allelic associations were evaluated with the chi-square test and the permutation test especially designed for adjustment of multiple testing. SNPs of LOXL1 and LOXL4 were not significantly associated with IA, while several SNPs of LOXL2 and LOXL3 showed nominally significant associations in IA patients. We detected an empirically significant association with one SNP of LOXL2 in familial IA patients after adjustment for multiple testing [chi(2) = 10.23, empirical P = 0.023, OR (95% CI) = 1.49 (1.17, 1.90)]. Furthermore, multilocus interaction was evaluated by multifactor dimensionality reduction analysis. We found that the SNPs of LOXL2 have an interactive effect with elastin (ELN) and LIM kinase 1 (LIMK1) that have been previously found to be associated with IA. In conclusion, one SNP of LOXL2 showed a significant association with IA individually, and we also detected a gene-gene interaction of LOXL2 with ELN/LIMK1, which may play an important role in susceptibility to IA. PMID- 17287950 TI - Cholesteryl ester transfer protein gene haplotypes, plasma high-density lipoprotein levels and the risk of coronary heart disease. AB - High-density lipoprotein cholesterol (HDL-C) is a known inverse predictor of coronary heart disease (CHD) and is thus a potential therapeutic target. Cholesteryl ester transfer protein (CETP) is a key protein in HDL-C metabolism such that elevated CETP activity is associated with lower HDL-C. Currently available HDL-C raising drugs are relatively ineffective and evidence suggesting the role of CETP in HDL-C levels has promoted the development of CETP inhibitors as potential therapeutic agents for CHD. We investigated three SNPs in the CETP gene in two cross-sectional community-based populations (n = 1,574 and 1,109) and a population of 556 CHD patients to determine if reduced CETP activity due to genetic variations in the CETP gene would increase HDL-C levels and reduce the risk of CHD. CETP genotypes and haplotypes were tested for association with lipid levels, CETP activity and risk of CHD. Multivariate analysis showed the common AAB2 haplotype defined by the G-2708A, C-629A and TaqIB polymorphisms, was consistently associated with reduced CETP activity and increased HDL-C levels. A mean increase in HDL-C levels of 0.16-0.24 mmol/l was observed in individuals with two copies of the AAB2 haplotype relative to non AAB2 carriers across all three populations (P < 0.001). A case-control study of males indicated no association between single SNPs or haplotypes and the risk of CHD. These results suggest that raising HDL-C via CETP inhibition may not alter risk of CHD. Randomized control trials are needed to determine whether CETP inhibition will in reality reduce risk of CHD by raising HDL-C. PMID- 17287951 TI - Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. AB - Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by mutations in either of two genes, TSC1 and TSC2. Point mutations and small indels account for most TSC1 and TSC2 mutations. We examined 261 TSC DNA samples (209 small-mutation negative and 52 unscreened) for large deletion/duplication mutations using multiplex ligation-dependent probe amplification (MLPA) probe sets designed to permit interrogation of all TSC1/2 exons, as well as 15-50 kb of flanking sequence. Large deletion/duplication mutations in TSC1 and TSC2 were identified in 54 patients, of which 50 were in TSC2, and 4 were in TSC1. All but two mutations were deletions. Only 13 deletions were intragenic in TSC2, and one in TSC1, so that 39 (73%) deletions extended beyond the 5', 3' or both ends of TSC1 or TSC2. Mutations were identified in 24% of small-mutation-negative and 8% of unscreened samples. Eight of 54 (15%) mutations were mosaic, affecting 34-62% of cells. All intragenic mutations were confirmed by LR-PCR. Genotype/phenotype analysis showed that all (21 of 21) patients with TSC2 deletions extending 3' into the PKD1 gene had kidney cysts. Breakpoints of intragenic deletions were randomly distributed along the TSC2 sequence, and did not preferentially involve repeat sequence elements. Our own 20-plex probe sets gave more robust performance than the 40-plex probe sets from MRC-Holland. We conclude that large deletions in TSC1 and TSC2 account for about 0.5 and 6% of mutations seen in TSC patients, respectively, and MLPA is a highly sensitive and accurate detection method, including for mosaicism. PMID- 17287952 TI - Mucosubstance histochemistry and pathogenesis of acquired cholesteatoma. AB - Mucosubstance histochemical study of 33 cholesteatoma tissues was performed to clarify the distribution and character of mucin in the perimatrix. Mean density of glandular cysts was 0.18 per mm(2). Mean frequency of ruptured cysts was 0.16 per cyst. Glandular cysts as well as hollow spaces in the perimatrix were filled with sulfomucin and sialomucin. Fragments of mucin were found in some macrophages and multinucleated giant cells. Since phagocytosis is host defenses attempt, the process indicates that mucin in the perimatrix is a cause of inflammation. Sialomucin infiltrated in the subepidermis where the epidermis formed papillary proliferation without an apparent sign of inflammation. Six glandular cysts were found in the matrix and the debris. They may have been eliminated from the perimatrix as a sequel to cholesteatoma growth. These findings suggest that embedded mucosa in the perimatrix may play a crucial role in pathogenesis of acquired cholesteatoma. PMID- 17287953 TI - Fetal MRI demonstrates glioependymal cyst in a case of sonographic unilateral ventriculomegaly. AB - We report a fetus of 28 weeks' gestation in which ultrasonography demonstrated unilateral ventriculomegaly and microcephaly. Fetal MRI demonstrated a simple, left paramedian occipital cyst with rarefaction of the corpus callosum and thinning of the adjacent cortical mantle. Ischaemia was suggested as the underlying pathogenesis, but autopsy after termination of pregnancy revealed a glioependymal cyst. This case highlights consideration of the rare diagnosis of glioependymal cyst when a cystic lesion associated with cerebral malformations, particularly dysgenesis of the corpus callosum, is demonstrated and fetal MRI suggests an ischaemic origin. PMID- 17287954 TI - Interactions between gray-sided voles (Clethrionomys rufucanus) and bilberry (Vaccinium myrtillus), their main winter food plant. AB - We compared the abundance, population structure and palatability of bilberry ramets on vole-free islands, islands with voles but no predators (predator-free islands) and mainland sites with both voles and predators. As expected, bilberry biomass was strongly correlated with the herbivory pressure exerted by the voles, since it was significantly lower on the mainland, and much (>80%) lower on the predator-free islands, than on the vole-free islands. However, another finding, which conflicts with hypotheses postulating that herbivory generally induces plant defenses, was that voles preferred ramets from predator-free islands. Bilberry plants were fairly tolerant to grazing since they compensated for some of the lost tissue by producing more new ramets. This response should promote stability in the plant-herbivore interaction by reducing the impact of past grazing on current food production and thus minimizing time delays in the interactions that could potentially generate population cycles. PMID- 17287955 TI - Multiscale wolf predation risk for elk: does migration reduce risk? AB - While migration is hypothesized to reduce predation risk for ungulates, there have been few direct empirical tests of this hypothesis. Furthermore, few studies examined multiscale predation risk avoidance by migrant ungulates, yet recent research reveals that predator-prey interactions occur at multiple scales. We test the predation risk reduction hypothesis at two spatial scales in a partially migratory elk (Cervus elaphus) population by comparing exposure of migrant and resident elk to wolf (Canis lupus) predation risk. We used GPS and VHF telemetry data collected from 67 migrant and 44 resident elk over the summers of 2002-2004 in and adjacent to Banff National Park (BNP), Canada. We used wolf GPS and VHF telemetry data to estimate predation risk as a function of the relative probability of wolf occurrence weighted by a spatial density model that adjusted for varying pack sizes. We validated the predation risk model using independent data on wolf-killed elk, and showed that combining wolf presence and spatial density best predicted where an elk was likely to be killed. Predation risk on summer ranges of migrant elk was reduced by 70% compared to within resident elk summer ranges. Because wolves avoided areas near high human activity, however, fine-scale selection by resident elk for areas near high human activity reduced their predation risk exposure to only 15% higher than migrants, a difference significant in only one of three summers. Finally, during actual migration, elk were exposed to 1.7 times more predation risk than residents, even though migration was rapid. Our results support the hypothesis that large-scale migrations can reduce predation. However, we also show that where small-scale spatial variation in predation risk exists, nonmigratory elk may equally reduce predation risk as effectively as migrants under some circumstances. PMID- 17287956 TI - CPAP adherence and partial upper airway obstruction during sleep. AB - Nasal continuous positive airway pressure (CPAP) is the treatment of choice in severe obstructive sleep-disordered breathing (SDB). Partial obstruction is usually considered as mild SDB with poor CPAP adherence. In a retrospective study, we investigated the occurrence of partial obstruction in 233 age and BMI matched male-female pairs and its impact on CPAP adherence after one year using static-charge-sensitive bed. Women had less SDB compared with men (21.8 vs 31.7% of time in bed (TIB), p < 0.001), less periodic breathing (5.8 vs 15.6%, p < 0.001) but tended to have more partial obstruction (10.5 vs 7.5%, p = 0.174). In women, partial obstruction accounted for 50.2% of breathing abnormalities, in men 37.2% (p < 0.001). CPAP adherence was 60.5% in women and 56.9% in men. When taking into account the proportion of partial obstruction (< or = 5 vs > 5% of TIB) or periodic breathing, there were no differences in women's CPAP adherence (p = 0.130 and p = 0.148, respectively). Men with periodic breathing over 5% of TIB tended to be more adherent to CPAP, (p = 0.052). The high occurrence of partial obstruction in both genders and particularly in women suggests that the apnea-hypopnea index underestimates the occurrence of SDB. There are no concerns of low adherence when treating symptomatic partial obstruction during sleep. Partial obstruction may not represent mild SDB but a different entity. PMID- 17287959 TI - The basal ganglia matching tools package for striatal uptake semi-quantification: description and validation. AB - PURPOSE: To design a novel algorithm (BasGan) for automatic segmentation of striatal (123)I-FP-CIT SPECT. METHODS: The BasGan algorithm is based on a high definition, three-dimensional (3D) striatal template, derived from Talairach's atlas. A blurred template, obtained by convolving the former with a 3D Gaussian kernel (FWHM = 10 mm), approximates striatal activity distribution. The algorithm performs translations and scale transformation on the bicommissural aligned image to set the striatal templates with standard size in an appropriate initial position. An optimization protocol automatically performs fine adjustments in the positioning of blurred templates to best match the radioactive counts, and locates an occipital ROI for background evaluation. Partial volume effect correction is included in the process of uptake computation of caudate, putamen and background. Experimental validation was carried out by means of six acquisitions of an anthropomorphic striatal phantom. The BasGan software was applied to a first set of patients with Parkinson's disease (PD) versus patients affected by essential tremor. RESULTS: A highly significant correlation was achieved between true binding potential and measured (123)I activity from the phantom. (123)I-FP-CIT uptake was significantly lower in all basal ganglia in the PD group versus controls with both BasGan and a conventional ROI method used for comparison, but particularly with the former. Correlations with the motor UPDRS score were far more significant with the BasGan. CONCLUSION: The novel BasGan algorithm automatically performs the 3D segmentation of striata. Because co registered MRI is not needed, it can be used by all nuclear medicine departments, since it is freely available on the Web. PMID- 17287961 TI - Spatial dose distributions in solid tumors from 186Re transported by liposomes using HS radiochromic media. AB - PURPOSE: A procedure for the measurement of spatial dose rate distribution of beta particles emitted by 186Re-liposomes in tumoral tissue, using HS GafChromic films, is presented. METHODS: HNSCC xenografts were intratumorally injected with 3.7 or 11.1 MBq of 186Re-liposomes, and planar gamma camera images were acquired to determine the liposome retention in the tumor. After imaging, rats were sacrificed and tumors were excised and processed in slices; HS film sections were placed between slices and the tumor lobe was reassembled. Tumors and films were kept in the dark at 4 degrees C for 18 h. After irradiation, films were removed and response was read using a transmission scanner. Films were analyzed to determine two-dimensional spatial dose rate distributions and cumulative dose volume histograms. Dose rate distributions were quantified using a 60Co calibration curve, the 186Re physical half-life, and a perturbation factor that takes into account the effect of the film protective layer. RESULTS: Dose rate distributions are highly heterogeneous with maximal dose rates about 0.4 Gy h(-1) in tumors injected with 3.7 MBq and 1.3 Gy h(-1) in tumors injected with 11.1 MBq. Dose volume histograms showed dose distributed in more than 95% and 80% of the tumor when injected with the lower and the higher activity, respectively. CONCLUSION: The described procedures and techniques have shown the potential and utility of HS GafChromic film for determination of dose rate distributions in solid tumors injected intratumorally with 186Re-liposomes. The film's structure and the liposomes' biodistribution must be taken into account to obtain quantitative dose measurements. PMID- 17287962 TI - Percutaneous nephrolithotomy in patients with normal versus impaired renal function. AB - This study aimed to compare the results of percutaneous nephrolithotomy (PCNL) in patients with impaired renal function (IRF) and normal renal function (NRF). Records of 300 consecutive patients who underwent PCNL from July 2002 to July 2005 were retrospectively reviewed. Nineteen patients (6.3%) had serum creatinine values higher than 1.5 mg/dl before surgery (IRF Group). Nineteen gender and age matched patients with normal renal function were chosen as controls (NRF Group). The surgical parameters, outcome, and complication rates were compared. The effect of PCNL on the renal function was assessed in patients with IRF. There were 13 male and 6 female patients in both groups. In the IRF group, seven patients had a solitary kidney and three had bilateral stones. Thus, PCNL was performed on 22 kidneys. No patients in the NRF Group had solitary kidney or bilateral stones and PCNL was performed on 19 kidneys. There were no statistically significant differences between the two groups for success and complication rates (P = 0.376 and P = 0.184, respectively). In a mean follow-up of 15.6 months, mean serum creatinine decreased from 2.8 to 2.6 mg/dl (P = 0.273) in patients of the IRF group. Similar stone clearance and complication rates were obtained with PCNL in patients with impaired and normal renal function. Surgery does not cause biochemical deterioration in patients with compromised renal function before treatment. PMID- 17287960 TI - Novel 111In-labelled bombesin analogues for molecular imaging of prostate tumours. AB - PURPOSE: It has been shown that some primary human tumours and their metastases, including prostate and breast tumours, overexpress gastrin-releasing peptide (GRP) receptors. Bombesin (BN) is a neuropeptide with a high affinity for these GRP receptors. We demonstrated successful scintigraphic visualisation of BN receptor-positive tumours in preclinical studies using the radiolabelled BN analogue [(111)In-DTPA-Pro(1),Tyr(4)]BN. However, the receptor affinity as well as the serum stability of this analogue leave room for improvement. Therefore new (111)In-labelled BN analogues were synthesised and evaluated in vitro and in vivo. METHODS AND RESULTS: The receptor affinity of the new BN analogues was tested on human GRP receptor-expressing prostate tumour xenografts and rat colon sections. Analogues with high receptor affinity (low nM range) were selected for further evaluation. Incubation in vitro of GRP receptor-expressing rat CA20948 and human PC3 tumour cells with the (111)In-labelled analogues resulted in rapid receptor-mediated uptake and internalisation. The BN analogue with the best receptor affinity and in vitro internalisation characteristics, Cmp 3 ([(111)In DTPA-ACMpip(5),Tha(6),betaAla(11),Tha(13),Nle(14)]BN(5-14)), was tested in vivo in biodistribution studies using rats bearing GRP receptor-expressing CA20948 tumours, and nude mice bearing human PC3 xenografts. Injection of (111)In labelled Cmp 3 in these animals showed high, receptor-mediated uptake in receptor positive organs and tumours which could be visualised using planar gamma camera and microSPECT/CT imaging. CONCLUSION: With their enhanced receptor affinity and their rapid receptor-mediated internalisation in vitro and in vivo, the new BN analogues, and especially Cmp 3, are promising candidates for use in diagnostic molecular imaging and targeted radionuclide therapy of GRP receptor-expressing cancers. PMID- 17287964 TI - [Therapy of follicular lymphoma]. AB - The treatment options for patients with follicular lymphoma have substantially improved in the last years, in particular with the development of innovative, antibody-based therapeutic strategies. Thus, the anti-CD20 antibody rituximab is one of the cornerstones in the therapy of follicular lymphoma today. It is used in combination with chemotherapy or as a single agent therapy for remission induction and as maintenance therapy. Encouraging results were also reported from monoclonal anti-CD20 antibodies, which are conjugated to radionuclides and exploit the high radiosensitivity of lymphomas. An example for this is the anti CD20 antibody ibritumomab tiuxetan, which is coupled to 90Yttrium and shows comparable activity to rituximab. Current trials are underway testing whether, for example, the sequential application of a rituximab/chemotherapy induction, myeloablative consolidation therapy followed by autologous stem cell transplantation and rituximab maintenance further improves the therapeutic outcome in follicular lymphoma, or even has curative potential in a subgroup of patients with this disease. PMID- 17287963 TI - RNR4 mutant alleles pso3-1 and rnr4Delta block induced mutation in Saccharomyces cerevisiae. AB - The PSO3 gene of Saccharomyces cerevisiae was molecularly cloned by complementing the cold-sensitivity phenotype of a pso3-1 mutant and was found to be allelic to RNR4, encoding one of the two DNA damage-inducible small subunits of the ribonucleotide reductase (RNR) complex. Compared to a rnr4Delta mutant that allows only very little mutation induction at very low doses of 254(nm) ultraviolet light (UVC), the pso3-1 mutant allele confers leakiness in that it permits some DNA damage-induced mutagenesis at low doses of UVC. Similarly, the pso3 mutant is slightly less sensitive to UVC than an rnr4Delta mutant. Cloning and sequencing of the RNR4 locus of the pso3-1 mutant revealed that its intermediate phenotype is attributable to a G --> A transition at nucleotide 352, leading to replacement of glycine by arginine [G118R] in the mutant's protein. Both RNR4 mutant alleles confer significantly less sensitivity to UVC than mutant alleles of non-UVC-mutable REV3, indicating that, apart from nucleotide excision repair, RAD6-dependent error-free DNA repair may still be functional. The phenotype of a strongly reduced UVC-induced mutagenesis for rnr4 mutant alleles has not yet been described; it suggests the importance of this gene for a fully functional RNR providing correct amounts of DNA precursor molecules, thereby, allowing translesion synthesis (error-prone) of UVC-damaged DNA. Stationary phase cells of the rnr4Delta mutant, but not of the original pso3-1 mutant, are swollen with a fourfold to eightfold increase in volume. The central role of RNR in DNA precursor metabolism and its complex regulation allow for several modes of suppression that may influence the phenotypes of RNR4 mutants, especially those containing the leaky pso3-1 mutant allele. PMID- 17287965 TI - [Asymptomatic 32 year old female smoker with persistent polyclonal lymphocytosis]. AB - A 32 year old female smoker (20 pack years) presented with an asymptomatic lymphocytosis of 13,000/nl and splenomegaly. The patient's blood smear showed an absolute lymphocytosis with 65% atypical lymphocytes. A total of 1% of the lymphocytes were bilobulated. Bone marrow histology and immunphenotyping of blood and bone marrow excluded leukemia and non-Hodgkin's lymphoma. IgH-CDR-3 PCR analysis revealed a polyclonal pattern. In summary, a persistent polyclonal B cell-lymphocytosis (PPBL) was diagnosed. The exact etiology of PPBL is still unclear, however, it is associated with a polyclonal raise in the lymphocyte count of CD27+IgD+-memory-B-lymphocytes due to a defect in apoptosis signaling and leukocyte homing to secondary lymphoid tissues. An association with cigarette smoking is obvious since all patients are smokers. From all published cases, only two developed a malignancy with an uncertain association with PPBL. We have been monitoring our patient for 6.5 years without any evidence of the development of a lymphoma. PMID- 17287966 TI - [Cardiac disease in patients with tumors and tumor therapy]. AB - Cardiac disease may occur as a direct complication of heart tumors or as an indirect complication of malignancies due to antineoplastic therapy. While primary cardiac neoplasias are rare, metastases to various cardiac structures are common. The cardiotoxicity of anticancer agents can lead to significant complications that may affect patients being treated for various non-cardiac neoplasias. The severity of such cardiovascular damage depends on many factors, such as the site of molecular action, the immediate and cumulative dose, the method of administration, and the presence of any underlying cardiac condition. Moreover, toxicity can be affected by concomitant radiation. Cardiotoxic effects can occur during the administration of the drug, but they may not manifest themselves until months or years after the patient has been treated. Since cardiovascular disease and cancer are both common, precise knowledge of therapeutic interactions and complications is necessary. PMID- 17287968 TI - [The Non-Contact Bridging Plate. A new fixed-angle device for the minimally invasive treatment of fractures of the proximal humerus--technique and preliminary results]. AB - BACKGROUND: Fractures of the proximal humerus are common in elderly patients, especially in osteoporotic bone. Requirements for surgical treatment are high primary stability to allow early functional physiotherapy. The Non-Contact Bridging (NCB) Plate for the proximal humerus (PH) is a new head locking system for treating fractures of the proximal humerus which allows minimally invasive surgery (MIS). METHODS: In this contribution, the implant and technique are described, as well as the analysis of the first clinical results after 61 procedures. RESULTS: In a mainly elderly patient population (mean: 73 years, range: 50-91 years) 61 minimally-invasive procedures were performed. The placement of screws led to a high primary stability. Primary implant failure occurred in one case (1.69%). The average constant score after 6 months was 62 points (age related mean 72). CONCLUSIONS: Using the MIS-technique, the NCB-PH plate provides high primary stability, allowing functional treatment without postoperative limitations. The first clinical results show a good functional outcome in a mainly elderly patient population. PMID- 17287967 TI - [Surgical management of vertebral column metastatic disease]. AB - The spine is the most frequent site of skeletal metastases. Among all spinal malignancies metastatic disease is most frequent and indicative of disseminating tumor disease. Depending on primary tumor entity, estimated survival time, general health status of the patient, presence of spinal instability and neurological deficits an oncological useful and patient-specific therapeutic intervention should be performed. New anterior approaches, resections and reconstruction techniques are making surgery a preferred method over radiation therapy. For differential indication of the multiple surgical treatment modalities prognostic scores are available to assist individual decision making. Indications for surgery include survival prognosis of minimum 3 months, intractable pain, progress of myelon compression and/or neurological deficits under radiochemotherapy, spinal instability and necessity for histological diagnosis. Resulting quality of life depends on efficient decompression of the spinal cord and restoration of spinal stability. To achieve these ultimate goals there are different anterior and posterior approaches, instrumentations and vertebral body replacement implants available. Preoperative embolization should be performed in hypervascular tumors, e.g., renal cell cancer. Vertebro /Kyphoplasty as a percutaneous intervention should be considered for painful multisegmental disease and symptomatic osteolysis without epidural tumor compression to reach analgesia and stability. A multidisciplinary approach in patient selection, decision making and management is an essential precondition for complication avoidance and acceptable quality of life. PMID- 17287969 TI - Endovascular optical coherence tomography ex vivo: venous wall anatomy and tissue alterations after endovenous therapy. AB - Endovascular optical coherence tomography (OCT) is a new imaging modality providing histology-like information of the venous wall. Radiofrequency ablation (RFA) and laser therapy (ELT) are accepted alternatives to surgery. This study evaluated OCT for qualitative assessment of venous wall anatomy and tissue alterations after RFA and ELT in bovine venous specimens. One hundred and thirty four venous segments were obtained from ten ex-vivo bovine hind limbs. OCT signal characteristics for different wall layers were assessed in 180/216 (83%) quadrants from 54 normal venous cross-sections. Kappa statistics (kappa) were used to calculate intra- and inter-observer agreement. Qualitative changes after RFA (VNUS-Closure) and ELT (diode laser 980 nm, energy densities 15 Joules (J)/cm, 25 J/cm, 35 J/cm) were described in 80 venous cross-sections. Normal veins were characterized by a three-layered appearance. After RFA, loss of three layered appearance and wall thickening at OCT corresponded with circular destruction of tissue structures at histology. Wall defects after ELT ranged from non-transmural punctiform damage to complete perforation, depending on the energy density applied. Intra- and inter-observer agreement for reading OCT images was very high (0.90 and 0.88, respectively). OCT allows for reproducible evaluation of normal venous wall and alterations after endovenous therapy. OCT could prove to be valuable for optimizing endovenous therapy in vivo. PMID- 17287970 TI - NOx (nitrite/nitrate) in patients with pediatric nephrotic syndrome. AB - To better understand the role of nitric oxide (NO) in pediatric nephrotic syndrome, we measured nitrite/nitrate (NOx) [NO2- and NO3-] in serum obtained from patients with several pediatric kidney diseases and investigated the locations of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). NOx in serum showed significantly higher levels than those in healthy controls (mean +/- SE: 297 +/- 55.7 vs. 158 +/- 13.1 pmol/10 microl). There was no significant difference between six patients with frequent relapse and five patients with nonfrequent relapse. The studies with immunostaining of iNOS and nitrotyrosine were negative for glomerulus in patients with nephrotic syndrome. Those findings suggest that NOx might indirectly influence disease progression in nephrotic syndrome. PMID- 17287971 TI - The founding and early history of the European Society for Paediatric Nephrology (ESPN). AB - The founding of the European Society for Paediatric Nephrology (ESPN) in 1967 was the milestone for pediatric nephrology in Europe. Now, at the beginning of the 21st century, more than 2,000 European pediatricians in 46 European countries work in the field of pediatric nephrology, and approximately 500 of these meet regularly at the annual ESPN meetings. Half of these 2,000 pediatricians work in about 200 specialized pediatric nephrology centers in tertiary care units, whereas the other half work in secondary pediatric care, with a special interest in common renal diseases. In this article the founding and early years of the ESPN are outlined and include the structure of the first ten annual ESPN meetings from 1967-1976. Historical reports are given by five pioneers who were first-hand witnesses of the development of pediatric renal care in Europe. PMID- 17287972 TI - Acute presentation of soft tissue vascular malformations: diagnosis with MR imaging. PMID- 17287973 TI - Negative effect of chromosome 1A on dough strength shown by modification of 1D addition in durum wheat (Triticum durum). AB - A monosomic addition line of Aegilops tauschii chromosome 1D in Triticum durum cv. PBW114 was produced in 1990. This line was self-pollinated and maintained for several generations while following the presence of chromosome 1D carrying the gene for red glume color. Cytological analysis indicated that two of the three derivative lines had substitution of chromosome 1D for 1A and another had substitution of chromosome 1D for 1B. One of these lines carried a pair of small chromosomes in addition to the 1D chromosome. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the derived lines showed the presence of high-molecular-weight (HMW) glutenin encoded by the Glu-D1 locus. The small chromosome found in one of the lines had nearly regular pairing and transmission to daughter nuclei. Fluorescent in situ hybridization (FISH) and analysis of molecular markers indicated that the small chromosome was derived from the short arm of chromosome 1A and carried the Glu-A3 locus. Microsatellite mapping based on the deletion bin map revealed that the small chromosome had terminal deletions on both the terminal and centromeric sides. The line with the small chromosome showed improvement of the sodium dodecyl sulfate (SDS) sedimentation value as compared to parent durum. However, the increase in SDS sedimentation value was more significant in the substitution line of chromosome 1D for 1A without the small chromosome. These facts suggest a negative effect of the Glu-A3 locus on dough strength. The sequence of the Glu-D1 locus from these lines showed that the HMW glutenin subunits were Ae. tauschii specific 2(t) + T2, which were previously found to be associated with poor rheological properties and bread loaf volume in synthetic hexaploid wheat by other workers. Thus, the significant improvement in the SDS-sedimentation value of the substitution line of 1D for 1A suggests that the absence of the negative effect of chromosome 1A on quality is more important than the presence of Glu-D1 of Ae. tauschii. PMID- 17287974 TI - The development of BAC-end sequence-based microsatellite markers and placement in the physical and genetic maps of soybean. AB - The composite map of soybean shared among Soybase, LIS and SoyGD (March 2006) contained 3,073 DNA markers in the "Locus" class. Among the markers were 1,019 class I microsatellite markers with 2-3 bp simple sequence repeats (SSRs) of >10 iterations (BARC-SSR markers). However, there were few class II SSRs (2-5 bp repeats with <10 iterations; mostly SIUC-Satt markers). The aims here were to increase the number of classes I and II SSR markers and to integrate bacterial artificial chromosome (BAC) clones onto the soybean physical map using the markers. Used was 10 Mb of BAC-end sequence (BES) derived from 13,473 reads from 7,050 clones constituting minimum tile path 2 of the soybean physical map ( http://www.soybeangenome.siu.edu ; SoyGD). Identified were 1,053 1-6 bp motif, repeat sequences, 333 from class I (>10 repeats) and 720 from class II (<10 repeats). Potential markers were shown on the MTP_SSR track at Gbrowse. Primers were designed as 20-24 bp oligomers that had Tm of 55 +/- 1 C that would generate 100-500 bp amplicons. About 853 useful primer pairs were established. Motifs were not randomly distributed with biases toward AT rich motifs. Strong biases against the GC motif and all tetra-nucleotide repeats were found. The markers discovered were useful. Among the first 135 targeted for use in genetic map improvement about 60% of class II markers and 75% of class I markers were polymorphic among on the parents of four recombinant inbred line (RIL) populations. Many of the BES based SSRs were located on the soybean genetic map in regions with few BARC-SSR markers. Therefore, BES-based SSRs represent useful tools for genetic map development in soybean. New members of a consortium to map the markers in additional populations are invited. PMID- 17287975 TI - Genetic variation of Bmy1 alleles in barley (Hordeum vulgare L.) investigated by CAPS analysis. AB - The enzyme beta-amylase is one of the most important hydrolytic enzymes in the grain of malting barley and is encoded by the gene Bmy1. To learn more about its structure and function, a total of 657 barley accessions including 541 Hordeum vulgare ssp. vulgare (HV), and 116 H. vulgare ssp. spontaneum (HS) were selected for the cleaved amplified polymorphic sequence (CAPS) analysis. These materials, covering all the 16 kinds of beta-amylase phenotypes screened from more than 8,500 accessions of the world barley germplasm, were classified into 13 CAPS types in the present study. A combined assay of phenotypes and CAPS types revealed extensive genetic variation at the Bmy1 locus, and in total 23 Bmy1 allele types were identified. The newly identified alleles (A-I-11, A-II-6, A-II 7, A-II-10, B-I-3, B-I-12 and B-I-13) provided us with a novel resource for barley breeding and Bmy1 study. In HV barley, six out of seven major allele types (C-II-1, B-II-2, B-Ia-3, A-II-5, A-II-6, and A-II-7) were shared with HS barley; the B-I-8 allele, which was predominant in north European cultivated barley, was found to be unique. Remarkably, very low Bmy1 genetic variation was detected in Tibetan barleys, which puts the validity of the hypothesis that Tibet is one of the original centers of cultivated barley into question. PMID- 17287976 TI - Two novel loci for pollen sterility in hybrids between the weedy strain Ludao and the Japonica variety Akihikari of rice (Oryza sativa L.). AB - Partial pollen sterility has been observed in hybrid progeny derived from a japonica cultivar, Akihikari and a weedy strain, Ludao, which naturally grows in Jiangsu province of east China. Cytological and histological analyses revealed that pollen abortion occurred largely at the bicellular pollen stage, primarily due to the gradual disaggregation of generative and vegetative cells. A genome wide analysis was further carried out in a backcross population of Akihikari //Ludao/Akihikari using a total of 118 simple sequence repeat (SSR) markers and an expressed sequence tag (EST) marker distributed on the entire rice linkage map. Two loci controlling hybrid pollen sterility, designated as S33(t) and S34(t), were located on chromosomes 3 and 11, respectively. Both loci were putatively different from all the previously reported gametophyte genes and hybrid pollen sterility loci. Interaction between the Ludao and Akihikari alleles at each of the two loci resulted in reduction of fertility in the pollens carring the Ludao alleles. To map the precise location of the major locus, S33(t), we selected 165 plants of the backcross population with pollen fertility higher than 80.0%, and assayed the recombinant events surrounding the S33(t) locus using newly developed SSR markers. The S33(t) was delimited to an 86 kb region between SSR markers RM15621 and RM15627. Sequence analysis of this region indicated that there were ten open reading frames. These results will be valuable for cloning this gene and marker-assisted transferring of the corresponding neutral allele in rice breeding programs. Furthermore, the origin of the weedy strain Ludao is discussed. PMID- 17287977 TI - Retinal pigment epithelial tear following intravitreal ranibizumab injections for neovascular age-related macular degeneration. AB - BACKGROUND: To report the development of retinal pigment epithelial (RPE) tear after intravitreal injection of ranibizumab (Lucentis, Novartis, Basel, Switzerland). METHODS: Case report with presentation of the fundus photography, fluorescein angiography (FA) and optical coherence tomography (OCT) findings. RESULTS: A 70-year-old man received intravitreal injections of ranibizumab for the treatment of occult choroidal neovascularisation (CNV) with fibrovascular pigment epithelial detachment due to age-related macular degeneration. One day after the third intravitreal ranibizumab injection, fundus examination showed a RPE defect at the foveal region. FA and OCT confirmed the presence of RPE tear sparing the fovea. No further progression of the RPE tear was observed after withholding subsequent ranibizumab injection and his right eye visual acuity remained at 20/100 at 3 months from the last injection. CONCLUSIONS: As with other anti-vascular endothelial growth factor treatment for CNV, RPE tear might occur after intravitreal ranibizumab injection even after previous uneventful intravitreal injections. PMID- 17287979 TI - The retinal arteriole to venule ratio: informative or deceptive? PMID- 17287980 TI - Twin pregnancy complicated with acute appendicitis and cholecystitis in the same gestational period. AB - INTRODUCTION: Acute appendicitis and symptomatic biliary stones are the most common indications for non-obstetrical surgical procedures during pregnancy. However, combination of these two clinical presentations in the same gestational period is anecdotal. CASE REPORT: A 30-year-old twin pregnant patient complicated with acute appendicitis followed by cholecystitis was reported with poor fetal outcomes. CONCLUSION: Despite appropriate management when two conditions, appendicitis and cholecystitis, occur in the same gestational period one after another complications might become inevitable. PMID- 17287981 TI - Pregnancy following oocyte donation in a woman with Noonan's syndrome and a balanced Robertsonian translocation a case report. AB - Successful pregnancy in Noonan's syndrome and balanced Robertsonian translocation women is extremely rare. This is because pregnancies in these women usually end in spontaneous miscarriage or termination before 24 weeks gestation due to severe congenital anomaly. In this article, we report the case of a 41-years-old woman with Noonan's syndrome and balanced Robertsonian translocation. She was delivered by an elective caesarean section at 38 weeks of a live male infant following a second attempt of in vitro fertilisation (IVF) and embryo transfer from donor oocytes. The use of donor eggs and IVF in these women means more of them will achieve successful term pregnancy as in this case. It is therefore important that Obstetricians understand this rare condition and optimise care. This case highlights some of the medical problems encountered by Obstetricians in managing patients in this high risk group. PMID- 17287982 TI - The effect of pregnancy on pre-existing osteopenia: a case report. AB - A 34-year-old Greek Cypriot lady (Mrs. AMC) P(2+0) booked at 10 weeks gestation with spontaneously conceived dizygotic twins. Her two previous uncomplicated pregnancies resulted in normal vaginal deliveries of male infants weighing 3.2 and 3.4 kg, respectively. Immediately following her second delivery, she underwent a manual removal of placenta (MRP) under general anaesthesia and sustained a fracture of the triquetral bone of her left wrist while being lifted off the operating table. Although she had complained of pain and restricted movement in her left hand after the MRP, the fracture remained undiagnosed for several weeks until an X-ray of her left wrist showed signs of delayed fracture healing of the triquetral bone. The pathological fracture was suggestive of osteoporosis during pregnancy but this was not investigated further at this stage. In 2004, she was referred to an orthopaedic surgeon with concern over a height loss of 3 cm in the preceding 6 months, as well as with generalised bony tenderness over her hips and lower back. Dual Energy X ray Absorptiometry (DEXA) to measure bone mineral density (BMD) revealed a T score of -1.6 SD (which is the WHO definition of osteopenia) in her right hip, which subsequently deteriorated to -1.8 SD (Table 1) PMID- 17287983 TI - The significance of intracardiac Doppler sonography in terms of fetal growth retardation. AB - INTRODUCTION: The proper function of the fetal heart is indispensable for the fetal development and the normal fetal growth. For prenatal medicine, Doppler sonography offers the possibility of a non-invasive method to examine the fetal cardiovascular function under normal and pathological circumstances. The role of the Doppler sonography is to identify those fetuses who have a high risk factor for developing a pre- or intrapartual asphyxia and therefore have to be delivered promptly. This study aimed at evaluating the clinical value of the intracardiac Doppler sonography (IDS) and at scrutinizing its usefulness during the supervision of the pregnancy of intrauterine growth restricted (IUGR) fetuses. MATERIALS AND METHODS: In a prospective research at the Medical School of Hanover, fetal IDS was applied to 174 pregnant women between the 21 and 37 weeks of gestation (WG). The e-wave and the a-wave, the E/A ratio, and the TVI (time velocity integral) were measured at the atrioventricular (AV) valves. The PV (peak velocity) as well as the TVI were determined at both the aortic and the pulmonary valve. Normal range curves were compiled for all measured parameters. RESULTS: Alongside a control group with untroubled gravidity, which consisted of 153 patients, IUGR fetuses, who formed a collective of 21 patients, were Doppler sonographically examined. While the gestational age advanced, an increase of both the e-wave and the a-wave above the AV-valves could be ascertained, which lead to an E/A ratio <1. Above the semilunar valves there was indicated a slight steady increase of the TPV, the PV as well as the TVI. Normal range curves, which largely correspond to those described in the literature, were compiled for the collective of the pregnancies without pathological findings (n = 153). In comparison to the standard collective, there were no significant differences from the collective of the growth restricted fetuses (n = 21). CONCLUSION: A temporal informational advantage of pathological intracardiac Doppler values for high risk pregnancies (IUGR) could not be retraced in the examined collective. Doppler sonography traces acute and chronic deficits, which are indicated by hemodynamic changes of the fetus's blood supply. The clinical importance of IDS as regards dystrophic fetuses has to be ascertained in continuative studies: In the stage of compensatory placental insufficiency (IUGR, arterial Doppler without ARED-flow, venous Doppler without pathological findings) the IDS cannot provide an informational advantage. Contrastingly, the diagnostic potential of the IDS as a screening method of fetal cardiac insufficiency during decompensative placental insufficiency (IUGR, arterial Doppler with ARED-flow, venous Doppler normal or pathological) remains indistinct and should therefore be prospectively evaluated within this high risk group and contrastingly compared to the significance of the venous Doppler sonography (informational advantage?). PMID- 17287984 TI - N terminus determinants of MinC from Neisseria gonorrhoeae mediate interaction with FtsZ but do not affect interaction with MinD or homodimerization. AB - While bacterial cell division has been widely studied in rod-shaped bacteria, the mechanism of cell division in round (coccal) bacteria remains largely enigmatic. In the present study, interaction between the cell division inhibitor MinC from Neisseria gonorrhoeae (MinC(Ng)) and the gonococcal cell division proteins MinD(Ng) and FtsZ(Ng) are demonstrated. Protein truncation and site-directed mutagenic approaches determined which N-terminal residues were essential for cell division inhibition by MinC(Ng) using cell morphology as an indicator of protein functionality. Truncation from or mutation at the 13th amino acid of the N terminus of MinC(Ng) resulted in loss of protein function. Bioinformatic analyses predicted that point mutations of L35P and L68P would affect the alpha-helical conformation of the protein and we experimentally showed that these mutations alter the functionality of MinC(Ng). The bacterial two-hybrid system showed that interaction of MinC(Ng) with FtsZ(Ng) is abrogated upon truncation of 13 N terminal residues while MinC(Ng)-MinD(Ng) interaction or MinC(Ng) homodimerization is unaffected. These data confirm interactions among gonococcal cell division proteins and determine the necessity of the 13th amino acid for MinC(Ng) function. PMID- 17287985 TI - Hyperthermic-induced hyperventilation and associated respiratory alkalosis in humans. AB - The purpose of this study was to determine if increased environmental heat leads to hyperthermic-induced hypocapnia and associated alkalosis during prolonged self paced cycling. Nine male cyclists completed three 100 km stochastic time trials in hot (34 degrees C), neutral (22 degrees C) and cold (10 degrees C) environments. Intermittent measurements of rectal and skin temperature, expired gases, blood pH, PaCO(2), PaO(2), and bicarbonate were made throughout. Rectal temperature increased significantly throughout all trials (P < 0.001) and was significantly correlated with increases in the ventilatory equivalent for carbon dioxide (Ve/ VCo2; r = 0.77; P < 0.001) and blood pH (r = 0.69; P < 0.05). Rectal temperature was also negatively correlated with a reduction in PaCO(2) (r = 0.80; P < 0.001). PaO(2) and bicarbonate concentration remained constant throughout all trials. This study has shown that prolonged self-paced cycling is associated with a hyperthermic-induced hyperventilation, causing a decrease in arterialized carbon dioxide tension and consequential respiratory alkalosis. PMID- 17287986 TI - Effect of prolonged unweighting of human skeletal muscle on neuromotor force control. AB - The purpose of this study was to determine the effect of 4 weeks of unilateral lower limb suspension (ULLS) on the fluctuations in motor output and the associated physiological changes. Subjects (n = 17) performed steady isometric plantarflexion (PF) and knee extension (KE) tasks, and KE shortening and lengthening contractions (intensity = 25% maximum). Spinal excitability of the soleus muscle was assessed via the H-reflex, muscle cross-sectional area (CSA) via MRI, along with EMG activity during the PF tasks. Following ULLS, isometric force fluctuations increased approximately 12% for the PF, and 22% for the KE (P < 0.05), with no difference in the pattern of PF muscle activation (P = 0.46). The unsteadiness of lengthening KE contractions increased 25% following ULLS (P = 0.03), while KE steadiness during shortening contractions was not altered (P = 0.98). Significant correlations were observed between the percent changes in PF isometric force fluctuations and H-reflex (r = 0.49, P = 0.04), and between the PF isometric force fluctuations and PF CSA (r = -0.61, P < 0.01). These findings suggest the effects of unweighting on neuromotor performance are muscle group and contraction type dependent, and that the disuse-paradigm altering muscle CSA and spinal excitability may serve to mediate the associated loss of steadiness. PMID- 17287987 TI - Y-chromosome genetic structure in sub-Apennine populations of Central Italy by SNP and STR analysis. AB - To define the Y-chromosome genetic structure in Apennine populations, 17 Y chromosome short tandem repeats (Y-STRs) and 37 Y-single nucleotide polymorphisms (Y-SNPs) were typed in 162 subjects living in the upland area of the Marches (Central Italy). A total number of 155 haplotypes (haplotype diversity was 0.9994) and 14 SNP haplogroups were observed. Testing high-resolution Y chromosome data sets, e.g. using Yfiler and SNPs, increases the discriminatory capacity in individual identification for forensic purposes. It is also useful in autochthonous population and micro-population studies to highlight the most informative loci for evolutionary aims. PMID- 17287988 TI - Interhemispheric interactions and redundancy gain: tests of an interhemispheric inhibition hypothesis. AB - In simple reaction time (RT) tasks, responses are faster when stimuli are presented to both the left and right visual hemifields than when a stimulus is presented to a single hemifield. Paradoxically, this redundancy gain with bilateral stimuli is enhanced in split-brain individuals relative to normals. This article reports three experiments testing an account of that enhancement in which normals' responses to bilateral stimuli are slowed by interhemispheric inhibition. In simple RT tasks, normal participants responded bimanually to left, right, or bilateral visual stimuli. In choice RT tasks, they responded to each stimulus with one hand, responding bimanually only when both stimuli were presented. Measurements of response forcefulness (Experiment 1) and electroencephalographic activity (Experiments 2 and 3) showed no evidence of the correlation patterns predicted by the hypothesis of interhemispheric inhibition. The results suggest that such inhibition is unlikely to be the explanation for enhanced redundancy gain in split-brain individuals. PMID- 17287989 TI - Motor unit conduction velocity during sustained contraction of the vastus medialis muscle. AB - The aim of the study was to analyze motor unit conduction velocity at varying force of the vastus medialis muscle during sustained contraction. Surface (8 electrode array) and intramuscular (two wire electrodes) EMG signals were recorded from the distal part of the dominant vastus medialis muscle of ten healthy male subjects. The subjects sat on a chair with the knee 90 degrees flexed and performed seven 180-s long contractions at forces in the range 2.5-30% of the maximal voluntary contraction force. For each force level, the discharge patterns of the newly recruited motor units with respect to the previous force level were identified from the intramuscular recordings and used as trigger for averaging the surface EMG signals. Motor unit conduction velocity was estimated from the averaged surface EMG. Average discharge rate at which motor units were analyzed was the same for each force level (mean +/- SD, 8.3 +/- 0.8 pulses per second). Motor unit conduction velocity at the beginning of the contraction and its rate of change over time increased with force (P < 0.05). Conduction velocity at the beginning of the contraction estimated from the interference surface EMG (4.44 +/- 0.66 m/s) and from single motor units (4.75 +/- 0.56 m/s) were positively correlated (R (2) = 0.46; P < 0.0001) but significantly different (P < 0.05). The results indicate that single motor unit conduction velocity and its rate of change during sustained contraction, assessed at a fixed discharge rate, depend on force level. PMID- 17287990 TI - Spatio-temporal contingency of saccade-induced chronostasis. AB - During fast, saccadic eye movements visual perception is suppressed. This saccadic suppression prevents erroneous and distracting motion percepts resulting from saccade induced retinal slip. Although saccadic suppression occurs over a substantial time interval around the saccade, there is no "perceptual gap" during saccades. The mechanisms underlying this temporal perceptual filling-in are unknown. When subjects are asked to perform temporal interval judgements of stimuli presented at the time of saccades, the time interval following the termination of the saccade appears longer than subsequent intervals of identical length. This illusion is known as "chronostasis", because a clock presented at the saccade target seemingly stops for a moment. We test whether chronostasis is a global mechanism that may compensate for the temporal gap associated with saccadic suppression. We show that a clock positioned halfway between the initial fixation point and the saccade target does not exhibit prolongation of the interval following the saccade. The characteristical distortion of temporal perception occurred only in the case of a clock being located at the saccade target. This result suggests a local, object-specific mechanism underlying the stopped clock illusion that might originate from a shift in attention immediately preceding the eye movement. PMID- 17287991 TI - Anisotropies in the gain of smooth pursuit during two-dimensional tracking as probed by brief perturbations. AB - Previous investigations suggest the gain of smooth pursuit is directionally anisotropic and is regulated in a task-dependent manner. Smooth pursuit is also known to be influenced by expectations concerning the target's motion, but the role of such expectations in modulating feedback gain is not known. In the present work, the gain of smooth pursuit was probed by applying brief perturbations to quasi-predictable two-dimensional target motion at multiple time points. The target initially moved in a straight line, then followed the circumference of a circle for distances ranging between 180 degrees and 270 degrees . Finally, the path reverted to linear motion. Perturbations consisted of a pulse of velocity 50 or 100 ms in duration, applied in one of eight possible directions. They were applied at the onset of the curve or after the target had traversed an arc of 45 degrees or 90 degrees . Pursuit gain was measured by computing the average amplitude of the response in smooth pursuit velocity over a 100 ms interval. To do so we used a coordinate system defined by the motion of the target at the onset of the perturbation, with directions tangential and normal to the path. Responses to the perturbations had two components: one that was modulated with the direction of the perturbation and one that was directionally nonspecific. For the directional response, on average the gain in the normal direction was slightly larger than the gain in the tangential direction, with a ratio ranging from 1.0 to 1.3. The directionally nonspecific response, which was more prominent for perturbations at curve onset or at 90 degrees , consisted of a transient decrease in pursuit speed. Perturbations applied at curve onset also delayed the tracking of the curved target motion. PMID- 17287992 TI - Laterality of interhemispheric inhibition depends on handedness. AB - There is some evidence that handedness is related to lateralisation of excitability in the motor system. We investigated lateralisation of interhemispheric inhibition (IHI), motor thresholds and short interval intracortical inhibition (SICI) and facilitation (SICF) in relation to handedness in 12 right (RH) and 13 left handed (LH) subjects. Because there is some controversy as to the optimal localisation to produce IHI we also compared IHI induced by conditioning the dorsal premotor cortex (dPM) versus primary motor cortex (M1) in ten RH. IHI was stronger following conditioning the motor dominant as compared to the motor non-dominant hemisphere in RH and LH. Motor thresholds were higher when elicited over the right hemisphere than over the left in both RH and LH, while SICI and SICF showed no differences between hemispheres or dependency from handedness. We hypothesize that IHI is a function of handedness perhaps reflecting predominant usage of the dominant hand, while lateralisation of thresholds and intracortical excitability are determined by other factors. PMID- 17287993 TI - Duration of the cue-to-pain delay increases pain intensity: a combined EEG and MEG study. AB - Expectation of pain is an important adaptive process enabling individuals to avoid bodily harm. It reflects the linking of past experience and environmental cues with imminent threat. In the present study, we examined changes in perceived pain contingent upon variation of the interval between an auditory cue and a subsequent painful laser stimulus. The duration of the cue-to-stimulus delay was systematically varied between 2, 4 and 6 s. Pain intensity and evoked brain responses measured by EEG and MEG recordings were analysed. Pain ratings from 15 subjects increased with longer cue-to-pain delays, accompanied by an increase in activity of the midcingulate cortex (MCC), as modelled from evoked EEG potential maps. On the other hand, MEG-based source activity in secondary somatosensory (SII) cortex remained unaffected by manipulation of the cue-to-stimulus interval. We conclude that activity in limbic structures such as MCC play a key role in the temporal dynamics of recruitment of expectation towards pain. Although this reaction is adaptive if the individual is able to avoid the stimulus, it is maladaptive if such opportunity is not present. PMID- 17287994 TI - Placebo analgesia: a PET study. AB - Placebo analgesia involves complex mechanisms and sometimes has a marked effect on patients in pain. In this study we examined changes in regional cerebral blood flow (rCBF) under three different conditions (resting, hot, painful) before and after placebo administration using H(2)(15)O and positron emission tomography in ten healthy subjects. In five subjects, placebo administration significantly decreased pain-intensity score (placebo responders), and rCBF in the medial prefrontal cortex (MPFC), posterior parietal cortex (PPC), and inferior parietal lobe (IPL) increased after placebo administration compared with before placebo administration under the painful condition. Furthermore, in the placebo responders, rCBF in the MPFC, PPC and IPL also increased under the resting condition (without sensory stimulation) after placebo administration compared with before placebo administration. However, there was no rCBF change under the rest condition in the placebo nonresponders after placebo administration. These results suggest that placebo analgesia has its effect under the resting condition and MPFC, IPL and PPC may have an important role in placebo analgesia. PMID- 17287995 TI - [Acute coronary syndrome. Guideline-conform management by regional and interregional care concepts]. AB - BACKGROUND: The acute coronary syndrome (ACS) with 16% is one of the most common indication for emergency missions. Care of ACS patients in the Heidelberg emergency service region has been carried out since the beginning of 2005 following an interdisciplinary developed concept based on the current guidelines of the German Society for Cardiology (DGK), the American College of Cardiology (ACC), the American Heart Association (AHA), the European Society of Cardiology (ESC) and the European Resuscitation Council (ERC). MATERIALS AND METHODS: Evaluation of the emergency diagnostic and therapeutic measures for the diagnosis of ACS before and after the introduction of the ACS care concept, was carried out retrospectively for the years 2004 (group 1) and 2005 (group 2) by electronic data processing of the records stored in the emergency medical services documentaion system (NADOK). RESULTS: In the years 2004 before (group 1, n=633) and 2005 after (group 2, n=628) introduction of the ACS care concept, there was a comparable basic diagnostic consisting of a 3-lead electrocardiogram (ECG; 95 versus 97%), manual blood pressure measurement (93 versus 95%) and pulse oxymetry (94 versus 91%) as well as a comparable proportion of patients who received a peripheral vene access (99 versus 100%). There were no significant differences between the two groups. However, after the introduction of the ACS concept, the 12-lead ECG was used significantly more often (49 versus 71%, p=0.0001). Furthermore, a guideline-conform medicinal treatment of ACS patients was used inceasingly more often for anticoagulation with heparin/acetylsalicylic acid (75 versus 84%,p=0.0001) and the use of beta-receptor blockers (32 versus 39%, p=0.009) after introduction of the ACS concept. CONCLUSIONS: The introduction of a regional care concept leads to an optimisation of guideline-conform prehospital treatment for ACS patients. PMID- 17287996 TI - Cognitive imitation in 2-year-old children (Homo sapiens): a comparison with rhesus monkeys (Macaca mulatta). AB - Here we compare the performance of 2-year-old human children with that of adult rhesus macaques on a cognitive imitation task. The task was to respond, in a particular order, to arbitrary sets of photographs that were presented simultaneously on a touch sensitive video monitor. Because the spatial position of list items was varied from trial to trial, subjects could not learn this task as a series of specific motor responses. On some lists, subjects with no knowledge of the ordinal position of the items were given the opportunity to learn the order of those items by observing an expert model. Children, like monkeys, learned new lists more rapidly in a social condition where they had the opportunity to observe an experienced model perform the list in question, than under a baseline condition in which they had to learn new lists entirely by trial and error. No differences were observed between the accuracy of each species' responses to individual items or in the frequencies with which they made different types of errors. These results provide clear evidence that monkeys and humans share the ability to imitate novel cognitive rules (cognitive imitation). PMID- 17287997 TI - A critical review of the physicalistic approaches of the mind and consciousness. AB - The aim of this paper is to construct a critical evaluation of the advantages and disadvantages of the physicalistic theory concerning mental phenomena and consciousness. Physicalism can, better than other theories, explain mental phenomena, such as intentionality and reasonability of human beings and other biological organisms. Modern neuroscience corroborates the conviction that the brain is a physical mind capable of giving meaning to, evaluating and further cognitively and behaviorally transforming complex aspects of the world. On the other hand, the emergence of consciousness from brain states seems to be a paradoxical, intransparent, physical coincidence hardly explained by the mental function of the brain at the physical level. Moreover, the intentionality and reasonability of psychic phenomena per se cannot be explained as a repercussion of the same attributes characterizing the brain function. In conclusion, the old debate between physicalism and other philosophical theories remains open. It can be expected that the progress of sciences will inspire novel approaches to the problem of the relations between matter, mind and consciousness. PMID- 17287998 TI - Intraoperative evaluation of sentinel lymph nodes for metastatic melanoma by imprint cytology. AB - BACKGROUND: Sentinel lymph node biopsy (SLN) has revolutionized nodal staging. Accurate intraoperative evaluation of SLN permits a single procedure, with lymphadenectomy being performed during the initial operative procedure when the SLN is positive. There is a paucity of literature on intraoperative imprint cytology (IIC) evaluation of the SLN in melanoma. The purpose of this article is to present an update to our experience with IIC for SLN in melanoma. METHODS: Melanoma patients had SLNs examined by IIC. SLNs were bisected, and imprints were made from each half. Imprints were stained with hematoxylin and eosin and with Diff-Quik. Paraffin-embedded sections were examined with multiple hematoxylin and eosin-stained sections from the SLNs in conjunction with immunohistochemical staining for S-100, Melan-A, and HMB-45 proteins. RESULTS: Metastases were identified in 40 (17%) of 229 patients. Of these, 13 patients were detected by IIC (sensitivity, 33%). The negative predictive value was 88%. No false-positive results were identified (specificity, 100%). The positive predictive value was 100%. The accuracy of IIC was 78%. The sensitivity for detecting macrometastases (>2 mm) was better than that for detecting micrometastases (< or =2 mm): 62% vs. 16% (P < .01). Patients with positive SLNs by IIC had lymphadenectomy under the same anesthetic. A total of 533 nonsentinel lymph nodes were identified in 42 patients. Only two patients (8%) had positive nonsentinel lymph nodes after a negative IIC. CONCLUSIONS: IIC is a viable alternative to frozen sectioning when intraoperative evaluation is desired. IIC is significantly more sensitive for macrometastases. IIC evaluation of SLNs in melanoma makes a single operative procedure possible for a significant proportion of patients with regional nodal metastases. PMID- 17288001 TI - Quality of life of patients operated on for lumbar stenosis: a long-term follow up. AB - BACKGROUND: We evaluated a sample of 28 patients surgically treated for lumbar stenosis (LS) four years after the first evaluation (length of the first follow up mean 44.6 months, range 15-88) in order to evaluate the long-term follow-up of Quality of Life (QoL) after surgical treatment as LS may greatly impair the patients' QoL. We previously assessed QoL in 30 patients operated on for LS four years before, by performing a retrospective follow-up through the Short-Form 36 Health Survey (SF-36). METHODS: In this current study we performed a phone call evaluation administering the SF-36 and the official Italian version of the North American Spine Society (NASS) lumbar spine outcome assessment instrument. FINDINGS: With regard to the SF-36 results at long term follow-up we observed a significant improvement of Physical Function, Bodily Pain, Mental Health and the Physical Composite Score with respect to the first follow-up. Conversely, Vitality worsened. Regarding the results of NASS an improvement of neurological symptoms was observed. Comparison of SF-36 mean scores in the current LS sample vs. the Italian normal population at the same age, showed similar QoL pattern. CONCLUSIONS: The long-term follow-up showed that patients operated on for LS continue to improve their QoL pattern even between the 4th and the 8th year after surgery. PMID- 17288002 TI - Kinetics of the cellular immune response following closed head injury. AB - BACKGROUND: The contribution of brain edema to brain swelling in cases of traumatic brain injury (TBI) remains a critical problem. We believe that inflammatory reactions may play a fundamental role in brain swelling following a head injury. Although possible roles of microglia activation and the release of mediators have been suggested, direct evidence of cellular immune reactivity in diffuse brain injury following closed head trauma is lacking. Accordingly, the objective of this study was to assess the temporal pattern of microglia activation and lymphocyte migration in an experimental model of TBI. METHOD: An impact acceleration TBI model was utilized to induce diffuse brain damage in adult Wistar rats. The animals were separated into three groups: unoperated controls, sham-operated controls and trauma group. At various times after TBI induction (5 min-24 h), rats were perfused transcardially. Sagittal brain sections were analyzed with immunohistochemical markers of CD3 to reveal the presence of T-lymphocytes, and by immunochemistry for the detection of CD11b to reveal microglia activation within the brain parenchyma. FINDINGS: In the control groups, scattered T-cells were found in the brain parenchyma. In the trauma group, TBI induced microglia activation and a transient biphasic T-cell infiltration of the brain parenchyma in all regions was found, beginning as early as 30 min post injury and reaching its maximum values at 45 min and 3 h after trauma induction. CONCLUSION: These results lead us to suggest that the acute response to severe head trauma with early edema formation is likely to be associated with inflammatory events which might be triggered by activated microglia and infiltrating lymphocytes. It is difficult to overestimate the clinical significance of these observations, as the early and targeted treatment of patients with severe head injuries with immunosuppressive medication may result in a far more favorable outcome. PMID- 17288003 TI - Broadband homonuclear chemical shift correlation at high MAS frequencies: a study of tanh/tan adiabatic RF pulse schemes without 1H decoupling during mixing. AB - At high magic angle spinning (MAS) frequencies the potential of tanh/tan adiabatic RF pulse schemes for 13C chemical shift correlation without 1H decoupling during mixing has been evaluated. It is shown via numerical simulations that a continuous train of adiabatic 13C inversion pulses applied at high RF field strengths leads to efficient broadband heteronuclear decoupling. It is demonstrated that this can be exploited effectively for generating through bond and through-space, including double-quantum, correlation spectra of biological systems at high magnetic fields and spinning speeds with no 1H decoupling applied during the mixing period. Experiments carried out on a polycrystalline sample of histidine clearly suggest that an improved signal to noise ratio can be realised by eliminating 1H decoupling during mixing. PMID- 17288004 TI - Learning to reason: a journey of professional socialisation. AB - One of the key attributes that health professional students and new graduates develop during professional socialisation is clinical reasoning ability. Clinical reasoning is a complex skill that is essential for professional practice. There is limited research specifically addressing how physiotherapists learn to reason in the workplace. The research reported in this paper addressed this gap by investigating how experienced physiotherapists learned to reason in daily practice. This learning journey was examined in the context of professional socialisation. A hermeneutic phenomenological research study was conducted using multiple methods of data collection including observation, written reflective exercises and repeated, semi-structured interviews. Data were analysed using phenomenological and hermeneutic strategies involving in-depth, iterative reading and interpretation to identify themes in the data. Twelve physiotherapists with clinical and supervisory experience were recruited from the areas of cardiopulmonary, musculoskeletal and neurological physiotherapy to participate in this study. Participants' learning journeys were diverse, although certain episodes of learning were common or similar. Role models, mentors and colleagues were found to be influential in the development of reasoning. An important implication for the professional socialisation of physiotherapists and other health professionals and for those involved in practice development is the need to recognise and enhance the role of practice communities in the explicit learning of clinical reasoning skills. PMID- 17288005 TI - Rhipicephalus appendiculatus and R. zambeziensis (Acari: Ixodidae) from Zambia: a molecular reassessment of their species status and identification. AB - The closely related species Rhipicephalus appendiculatus and R. zambeziensis co occur in a wide area in Zambia. In this area, specimens of both species have been collected on the same individual host at the same time. In addition, specimens that are morphologically intermediate between R. appendiculatus and R. zambeziensis have been found in this area. These observations cast some doubt on the species status of R. appendiculatus and R. zambeziensis. Because the two taxa have varied influences on the epidemiology of East Coast fever (ECF), a cattle disease for which they act as vectors, it is essential that their taxonomic status is clarified and their identification is accurate. Therefore a phylogenetic analysis of nucleotide sequences of the ITS2 and a fragment of the mitochondrial 12S rDNA was performed to reassess the specific status of both taxa. This revealed two well supported clades coinciding with R. appendiculatus and R. zambeziensis as two separate species. In order to facilitate species identification a PCR-RFLP diagnostic assay was developed based on BauI digestion of the ITS2 gene. This assay produced clear diagnostic banding patterns for the two species and is applicable over a wide range of both species' distribution. PMID- 17288006 TI - Arsenic mineralization, source, distribution, and abundance in the Kutahya region of the western Anatolia, Turkey. AB - Environmental exposure to arsenic (As) in the Kutahya region of the western Anatolia, Turkey has been reported to cause various types of arsenic-associated skin disorders (Dogan, Dogan, Celebi, & Baris, 2005). A geological and mineralogical study was conducted to find the sources and distribution of the As. Geogenic (background) levels were measured in samples collected from various sources in the Gediz, Simav, Tavsanli, Emet, Yoncali, Yenicekoy, and Muratdagi areas of the Kutahya region. Based on this analysis, we determined that natural sources are a domineering factor affecting the distribution of As, which was found: (1) mainly in evaporitic minerals, including colemanite (269-3900 ppm) and gypsum (11-99,999 ppm), but also in alunite (7-10 ppm) and chert (54-219 ppm); (2) in secondary epithermal gypsum, which has a high concentration of As in the form of realgar and orpiment along fracture zones of Mesozoic and Cenozoic carbonate aquifers; (3) in rocks, including limestone/dolomite (3-699 ppm) and travertine (5-4736 ppm), which are relatively more enriched in As than volcanics (2-14 ppm), probably because of secondary enrichment through hydrological systems; (4) in coal (1.9-46.5 ppm) in the sedimentary successions of the Tertiary basins; (5) in thermal waters, where As is unevenly distributed at concentrations varying from 0.0-0.9 mg/l. The highest As concentrations in thermal water (Gediz and Simav) correlate to the higher pH (7-9.3) and T (60-83 degrees C) conditions and to the type of water (Na-HCO3-SO4 with high concentration of Ca, Mg, K, SiO2, and Cl in the water). Changes in pH can be related to some redox reactions, such as the cation exchange reactions driving the dissolution of carbonates and silicates. Fe-oxidation, high pH values (7 9.3), presence of other trace metals (Ni, Co, Pb, Zn, Al), increased salinity (Na, Cl), high B, Li, F, and SiO, high Fe, SO4 (magnetite, specularite-hematite, gypsum), and graphite, and the presence of U, Fe, Cu, Pb, Zn, and B, especially in the Emet, Gediz, and Simav areas, are the typical indicators for the geothermally affected water with high As content. A sixth source of As in this region is the ground (0.0-10.7 mg/l) and the surface waters (0.0022-0.01 mg/l), which are controlled by water-rock interaction, fracture system, and mixing/dilution of thermal waters. The high As concentration in groundwater corresponds to the areas where pathological changes are greatest in the habitants. Arsenic in ground water also effects ecology. For example, only Juriperus oxycedrus and J. varioxycedrus types of vegetation are observed in locations with the highest concentration of As in the region. Branches and roots of these plants are enriched in As. PMID- 17288007 TI - Environmental radon studies in Mexico. AB - Radon has been determined in soil, groundwater, and air in Mexico, both indoors and outdoors, as part of geophysical studies and to estimate effective doses as a result of radon exposure. Detection of radon has mainly been performed with solid state nuclear track detectors (SSNTD) and, occasionally, with active detection devices based on silicon detectors or ionization chambers. The liquid scintillation technique, also, has been used for determination of radon in groundwater. The adjusted geometric mean indoor radon concentration (74 Bq m-3) in urban developments, for example Mexico City, is higher than the worldwide median concentration of radon in dwellings. In some regions, particularly hilly regions of Mexico where air pollution is high, radon concentrations are higher than action levels and the effective dose for the general population has increased. Higher soil radon levels have been found in the uranium mining areas in the northern part of the country. Groundwater radon levels are, in general, low. Soil-air radon contributing to indoor atmospheres and air pollution is the main source of increased exposure of the population. PMID- 17288008 TI - The investigation of metal concentrations in street dust samples in Aqaba city, Jordan. AB - The concentrations of metals (Fe, Zn, Cu, Cr, Pb, Cd, Ni, Mn and Co) in 140 street dust samples were collected from Aqaba city, Jordan. These samples were determined using flame atomic absorption spectrophotometry after digestion with aqua regia. The highest levels of metal concentrations were found in the samples from heavy traffic. While the lowest levels of metal ions were noted in the street dust samples from hospital and health centers and school gardens. The results of this study were compared with several cities around the world. The levels of the metal concentrations found were generally below the mean world-wide values of street dust samples. Metal values in urban street dust samples were several times higher than the control levels. The statistical analyses were applied to the data matrix to determine the analytical results and to identify the possible source of pollution in the studied area. Correlations between the metal concentrations of the street dust samples were obtained. Factor analysis showed that the area was mainly influenced by three sources, namely lithogenic, traffic, and industrial. PMID- 17288009 TI - Variations between rice cultivars in root secretion of organic acids and the relationship with plant cadmium uptake. AB - To attempt to understand certain mechanisms causing the variations between rice cultivars with regard to Cd uptake and accumulation, pot soil experiments were conducted with two rice cultivars at different levels of Cd, i.e., 0 (the control), 10, 50 mg Cd kg(-1 )soil. The two rice cultivars differ significantly with regard to Cd uptake and accumulation. Root secretions of low-molecular weight organic acids (LMWOA) for each treatment were measured with ion chromatography. The results showed that LMWOA concentrations in the soil planted with Shan you 63 (a high soil Cd accumulator) were all higher than those in the soil planted with Wu yun jing 7 (low soil Cd accumulator) at different soil Cd levels, although the magnitudes of the differences varied for individual LMWOA and depend on soil Cd concentrations. For all six LMWOA, there were significant differences at P < 0.05 or < 0.01 levels for soils treated with 10 and 50 mg kg( 1) Cd. The magnitude of the differences was greater under soil Cd treatments, especially at relatively low levels (for example, 10 mg Cd kg(-1) soil), than in the control. Acetic acid and formic acid constituted more than 96% of the total concentration of the six LMWOA, while citric acid constituted only about 0.1%. The rice cultivar with higher concentrations of LMWOA in soil accumulated more Cd in the plants. The results indicate that LMWOA secretion by rice root, especially in Cd-contaminated soils, is likely to be one of the mechanisms determining the plant Cd uptake properties of rice cultivars. PMID- 17288010 TI - Fluoride distribution in the environment along the gradient of a phosphate fertilizer production emission (southern Brazil). AB - Airborne fluoride was determined in the rainwater, surface soil and groundwater along a gradient of emission of a phosphate fertilizer factory in Rio Grande, southern Brazil. Concentrations of fluoride in rainwater and groundwater achieved 3 mg l(-1) and 5 mg l(-1), respectively, and were dependent on pH. The fluoride deposited from emissions accumulated in a superficial horizon of soil in quantities comparable to those in the manufactured end-products--up to 23,000 mg kg(-1). Fluoride distribution in the environment is controlled by physical chemical parameters of emission, rain intensity and soil properties. The highest fluoride concentrations were registered at a close distance of up to 2 km from the factory. The distribution of fluoride in groundwater resembled the same distribution in rainwater due to the high permeability of the local soils. Fluoride penetration to the groundwater also depended on the type of vegetation cover. The groundwater in woodland areas was less affected by contamination of fluoride than in the grassland areas, most probably because of the influence of eucalyptus throughfall, which increases the pH of wet precipitates. PMID- 17288013 TI - Retraction notice to: Facial expressions of emotion reveal neuroendocrine and cardiovascular stress responses. PMID- 17288012 TI - A preliminary study on the effect of pharmacist counseling on awareness of and willingness to quit smoking in Malaysian population. AB - OBJECTIVES: This paper presents an outcome of pharmacist counseling among Malaysian smokers for their awareness of and willingness to quit smoking. METHOD: It was a cross-sectional study during a 3-day public health campaign at a shopping complex. Each self-referred participant was asked to complete a questionnaire apart from the question regarding improvement, and if any in their awareness and willingness to quit smoking, were asked to respond after counseling. Pharmacists counseled each participant about smoking cessation strategies and smoking related diseases. The data were analyzed by chi2 test. RESULTS: Among respondents, 25.5% had been smoking for more than 10 years, 31% for 5-10 years, 25.4% for 2-5 years and 18.3% for 1-2 years. The participants declaring no awareness about smoking were 22.9%, with little awareness 44.3%, having moderate awareness 25.7% and with considerable awareness were 7.1%. After counseling, 4.1% revealed unawareness, 17.8% little awareness, 43.8% moderate and 34.2% had considerable awareness on the above aspects. The post counseling awareness on smoking was observed to be significantly higher (P < 0.01). Among smokers studied, 67% showed willingness to quit smoking. CONCLUSION: Increase in awareness of and willingness to quit smoking reflects that pharmacist counseling seems to be helpful in cessation of smoking. PMID- 17288014 TI - New Alzheimer's clinical trials to be undertaken by NIA nationwide consortium. PMID- 17288015 TI - Response to "The impact of tuberculosis on Zambia and the Zambian nursing workforce". PMID- 17288016 TI - Call light use. PMID- 17288017 TI - Giant cell arteritis and polymyalgia rheumatica. PMID- 17288018 TI - CMS plans changes in guidelines for consent, alcohol-based preps. PMID- 17288019 TI - Health plan termination--bankruptcy--automatic stay--COBRA. In re Health Management Limited Partnership. AB - Even though an insurer provided telephone notice of termination of a group health plan's insurance coverage for failure to pay the required premium on the same day the employer filed a bankruptcy petition and gave written notice after the petition was filed, it did not violate the bankruptcy code's automatic stay provision. This is because a special payment plan provided for an extended grace period and automatic termination upon failure to pay the premium in full by the end of that period, and the final due date was before the debtor filed the petition. Thus, termination occurred automatically before the bankruptcy petition was filed. The insurer is not the plan administrator and is not obligated to provide COBRA notice to the debtor's employees, especially since the employees could not elect to continue coverage under a group health plan when the insurance coverage had been terminated. An employee's right to elect to continue coverage under the employer's group plan presumes there is coverage available to continue. PMID- 17288020 TI - $4 billion problem. Hospitals protest proposed rule on medicaid transfers. PMID- 17288021 TI - Genes and lifestyle: are we victims of our own success? PMID- 17288022 TI - Low back pain: treatment and prevention. PMID- 17288023 TI - Mind and body: do music, imagery, touch, or prayer improve cardiac care? PMID- 17288024 TI - On call. Whenever I ride my bike for more than an hour or so, I notice numbness in my penis. I know that can lead to impotence, so I've stopped taking long rides. But now I see some policemen in my town patrolling on bikes all day long. Will they end up with problems? PMID- 17288025 TI - On call. I was recently diagnosed with high blood pressure. I reread your articles from December 2003 and January 2004 and found them very helpful. I was hoping that my doctor would prescribe a diuretic, but she said it would not be safe because I'm allergic to sulfa drugs. What do you think? PMID- 17288026 TI - Pediatricians advocate more playtime for children. PMID- 17288027 TI - Child health. In the news: a vaccine for hayfever?...and a new treatment for ear infections? PMID- 17288028 TI - A caution about breast feeding while using codeine. PMID- 17288029 TI - Child safety. Smoke alarm: parent's voice works better than the standard tone. PMID- 17288030 TI - A politics of eating: feasting in early Greek society. PMID- 17288031 TI - The times they are a-changing. New directions in HIV therapy. PMID- 17288033 TI - Side effect chart. An abbreviated at-a-glance guide to potential HIV drug side effects. PMID- 17288032 TI - The eleventh annual HIV drug guide. PMID- 17288034 TI - Drug interactions chart. An abbreviated at-a-glance guide to HIV drug interactions. PMID- 17288035 TI - Cloning and characterization of a novel sulfate transporter gene from radish (Raphanus sativus L.). AB - A putative sulfate transporter gene, RSultr3.2A, was identified from radish (Raphanus sativus L.). The RSultr3.2A gene encodes a polypeptide of 651 amino acids with a calculated molecular mass of 71701 Da. The deduced amino acid sequence preserves the common motifs of the sulfate transporters and exhibits a high degree of homology to other plant sulfate transporters. RSultr3.2A was not induced by sulfur starvation and was expressed in roots, stems, leaves, flowers and young pods, suggesting a possible need for the nonregulated and constitutive sulfate transport system of the plant. The RSultr3.2A is a single copy gene in the radish genome. A genomic sequence information corresponding to RSultr3.2A cDNA was found by PCR and sequencing. Comparison of cDNA and genomic sequences revealed that the coding sequence of RSultr3.2A consisted of 12 exons. In addition, another cDNA (RSultr3.2B) from radish young pods was found. As compared with RSultr3.2A, RSultr3.2B encodes a 499 amino acid protein with modifications in the carboxy-terminus. Sequence analysis suggested an occasional donor splicing site mutation (GT to TT) in the RSultr3.2A gene from radish young pods leading to the truncated cDNA RSultr3.2B. PMID- 17288036 TI - [Loss of weight and acute abdominal pain in a 38-year-old psychostimulant abuser]. AB - MATERIAL AND METHODS: A 38-year-old psychostimulant abuser was admitted to hospital after syncope. He had lost much of his weight over the last 6 months, had abdominal pain the last 10 days and bloody diarrhoea and hypotension upon admittance. The abdomen was soft and non-tender. Due to renal failure and metabolic acidosis with base excess of -16 to -22 mmol/L and lactate from 9.5 to 16 mmol/L, haemodialysis was given twice. Acidosis worsened. He suffered from respiratory arrest twice and was resuscitated once before a laparotomy 30 hours after admittance revealed total ischemia of the bowels. The patient died. At autopsy the coeliac trunk was compressed by thrombi in a dissecting space. A dissection was also found from the proximal aorta to the common iliac arteries. The heart was hypertrophic and weighed 640 g. DISCUSSION: Bowel ischemia due to dissecting arteries may have caused the dramatic weight loss. Cardiac hypertrophy is often found after cocaine and amphetamine misuse, and frequent hypertensive episodes may cause aortic dissection. INTERPRETATION: Abdominal pain and lactic acidosis should bring bowel ischemia to mind even if the abdomen is non-tender. Drug abuse also in young persons is associated with serious cardiovascular pathology. PMID- 17288037 TI - [Intestinal ischemia--often overlooked]. PMID- 17288038 TI - [Substance abuse and specialist health services]. PMID- 17288039 TI - Californian transplant conundrum. PMID- 17288040 TI - New initiatives improve cancer care for Native Americans. PMID- 17288041 TI - Finding better ways to deliver taxanes to cancer cells. PMID- 17288043 TI - 50% of some cancers in Europe are "avoidable". PMID- 17288042 TI - Fatigue with sunitinib-induced hypothyroidism. PMID- 17288044 TI - Octreotide: no benefit in advanced liver cancer. PMID- 17288045 TI - Consolidation treatment for ALL-which is best? PMID- 17288046 TI - Gene signature for predicting NSCLC outcome. PMID- 17288047 TI - 29th Annual Meeting of the San Antonio Breast Cancer Symposium, TX, USA; Dec 14 18, 2006. PMID- 17288048 TI - Comparing the implementation of CPOE in two Dutch hospitals revisited. PMID- 17288049 TI - Characterization of a lectin from Gonatanthus pumilus D. Don having anti proliferative effect against human cancer cell lines. AB - A monocot araceous lectin from tubers of Gonatanthus pumilus (GPL) wa earlier purified in our laboratory and reported as T-cell mitogen having homotetrameric structure with subunit molecular mass of 13 kDa. Besides asialofetuin as reported earlier, in the present study it was also inhibited by N-acetyl-D-lactosamine but was non-reactive towards mannose or its derivatives. The lectin is rich in acidic amino acids and cysteine is completely absent. Chemical modification of GPL revealed requirement of tryptophan and tyrosine for lectin sugar interaction. The secondary structure content of GPL, as estimated with CD spectrum in K2D programme, has 73% alpha-helix, 26% beta-sheet and 38% random contributions. Fluorescence spectrum of the lectin solution at 280 nm was typical for tryptophan residues buried inside the protein. Lectin activity decreased when treated with denaturants like guanidine-HCL, urea and thiourea. GPL inhibited the growth of three plant pathogenic fungi namely Colletotrichum lindemuthianum, Fusarium oxysporum and Botrytis cinerea. Out of 11 human cancer cell lines tested, GPL significantly inhibited proliferation of five lines viz. Colo-205, IMR-32, HCT 15, SK-N-SH and HT-29. PMID- 17288050 TI - Colonoscopy screening for detection of advanced neoplasia. PMID- 17288051 TI - DHEA and testosterone in the elderly. PMID- 17288052 TI - [A new Sumerian medical prescription]. PMID- 17288053 TI - [Sumerian medical prescriptions]. PMID- 17288054 TI - Medical education--professionalism. PMID- 17288055 TI - [New incursions in the vocabulary of Theodorus Priscianus: technical and late verbal forms]. PMID- 17288056 TI - [Perceptions of the plague in Christian Byzantium and the Muslim World]. PMID- 17288057 TI - [New evidence concerning Pelagonius' Ars veterinaria]. PMID- 17288058 TI - Plato and medical texts: Symposium 185c - 193d. PMID- 17288059 TI - Alchemy and medicine in the Middle Ages. PMID- 17288060 TI - [University courses in pharmacy in the Czech Republic]. AB - The paper analyzes and compares the interest of applicants for the admission to the university courses in Pharmacy in the Czech Republic from the viewpoint of their number, sex, and other indices. It also characterizes the courses and discusses the requirements for pharmacists (dispensing chemists) and their possible professional careers. PMID- 17288061 TI - [Measurement of adhesive properties of polymers in vitro]. AB - Adhesive force of branched oligoesters under the in vitro conditions was studied by measuring the maximal force necessary to separate the tested sample from the base (F(max)) under different testing conditions. Branched oligoesters were synthesized from lactic and glycolic acids in the molar ratio 1:1, and from mannitol or dipentaery thritol as the branching components in concentrations of 3%, 5% or 8%. To decrease viscosity and thus to facilitate the workability and administration, triethyl citrate (TEC) in a concentration of 30% was employed. Polymeric systems for adhesive force measurements were prepared by melting oligoesters in a micro oven and by homogenization with TEC. Adhesive force was measured on a material testing device T1-FR050TH.A1K Zwick/Roell at the set rate of separation 10 mm/min or 100 mm/min, contact force 10 N or 20 N, and a period of contact of the sample with the base of 5 s or 10 s. The adhesive force of branched oligoesters was found to be significantly higher than the adhesive force of gelatine gels, methylcellulose, carmelose sodium salt or sodium carbomer salt. Dipentaerythritol-branched oligoesters exerted higher adhesive force than mannitol-branched oligoesters. The value of adhesive force was increased with growing concentration of the branching component in the oligoester. Of the experimental parameters tested, a statistically significant influence of the separation rate of the sample from the base on the magnitude of F(max) was observed. The influence of different periods of contacts was manifested only in some samples, and the influence of different contact forces on F(max) value was not demonstrated in any sample. PMID- 17288062 TI - [Liquid ginger extract: technology of production and quality evaluation]. AB - The paper aimed to elaborate the technology of the production of a liquid ginger extract and to select and verify the methods of quality evaluation of the final preparation. The experiment revealed 70% ethanol as a suitable extraction agent. The optimal conditions for the development of an extract of good quality are established when the herbal drug is crushed to form particles passing through a sieve with a mesh size of 4000 microm, the extraction method is repercolation with the division of the charge of the drug in the relation 5:3:2, and the liquid flows from the percolator at a rate of 0.2ml/min/100 g of the drug. The presence of amino acids, saccharides, glycosides, reducing agents, phenolic substances, and alkaloids in the finished extract was demonstrated by means of colour or precipitation reactions. Thin-layer chromatography was employed to demonstrate gingerols and shogaols. Evaporation residue, ethanol concentration, and the amount of essential oils were determined quantitatively. PMID- 17288063 TI - [Potentiometric determination of aqueous dissociation constants of 2-,3-,4-{3-(4 benzhydryl-piperazine-1-yl)-2-hydroxy-propoxy}-phenylcarbamic acid alkylesters, water insoluble potential blockers of beta-adrenergic receptors]. AB - Apparent ionization constants (W(s)pK(a)) of potential drugs, a series of twelve protonated bases, 2-,3-,4-{3-(4-benzhydryl-piperazine-1-yl)-2-hydroxy-propoxy} phenylcarbamic acid alkylesters dihydrochlorides, were determined by automated potentiometric titrations in mixtures water - methanol. Aqueous pK were assessed by means of Yasuda-Shedlovsky equation. Approach for pKa determination was evaluated using trimecaine hydrochloride as the model compound. The first values of ionization constants ranged approximately from 2.7 to 3.2, the second ones from 6.5 to 7.2. Only a slight decrease in ionization constants with the number of carbon atoms was observed in homological series. Experimentally determined dissociation constants were compared with the values predicted by the computer program SPARC. PMID- 17288064 TI - [Continuous education of pharmacists in the Czech Republic. 2nd cycle 2002-2005]. AB - The paper deals with continuous education of pharmacists in the Czech Republic in 2002-2005 (2nd cycle). It surveys the seminars organized within the framework of continuous education, their number, topics, and lecturers. A total number of 232 professional seminars took place, which included 339 lectures, mainly on pharmacology (76.1%). PMID- 17288066 TI - Voluntary partial capitation: the Community Nursing Organization Medicare demonstration. AB - In a recently concluded Medicare demonstration, Community Nursing Organizations (CNOs) received capitated payment to provide a subset of Medicare services through a nursing case management delivery system. Demonstration participation was voluntary, both for CNOs and recruited beneficiaries, raising several challenging issues associated with selection. We investigate provider and beneficiary selection, as well as Medicare costs, using multiple evaluation methodologies. We find that CNO enrollment is associated with increased payment by Medicare for CNO-covered services. Results showing CNO enrollees to be more costly to Medicare for non-CNO services are consistent with cost shifting, but could also be accounted for by biased provider selection into the demonstration. PMID- 17288065 TI - Return on investment in disease management: a review. AB - The results of 44 studies investigating financial impact and return on investment (ROI) from disease management (DM) programs for asthma, congestive heart failure (CHF), diabetes, depression, and multiple illnesses were examined. A positive ROI was found for programs directed at CHF and multiple disease conditions. Some evidence suggests that diabetes programs may save more than they cost, but additional studies are needed. Results are mixed for asthma management programs. Depression management programs cost more than they save in medical expenses, but may save money when considering productivity outcomes. PMID- 17288067 TI - Estimating payment error for Medicare acute care inpatient services. AB - CMS recently assumed responsibility for estimating the Medicare fee-for-service (FFS) error rate from the Office of the Inspector General (OIG). Here, the method used to calculate national, by State, and by error type, estimates for the inpatient acute care portion of this rate is presented. For fiscal years (FYs) 1998 and 2000 discharges, national estimates for the net error rate were 2.6 and 2.8 percent, respectively, about $2 billion annually. Wide variation in State rates illustrates that estimates to the State level are essential for targeting and monitoring interventions to reduce improper Medicare inpatient acute care reimbursements. PMID- 17288068 TI - Evaluating the effect of translation on Spanish speakers' ratings of Medicare. AB - This study examined the equivalence of the English and Spanish versions of the Medicare Consumer Assessment of Health Plans Study (CAHPS) fee-for-service (FFS) survey among 2,996 Hispanic Medicare beneficiaries. Multigroup confirmatory factor analyses indicated that with few exceptions the factor structures were very similar for the English and Spanish surveys. However, item response theory based methods for investigating differential item functioning (DIF) revealed that several items demonstrated threshold-related DIF, suggesting that respondents in the two languages utilized the response options for the items differently. The results of this study suggest the need for future qualitative research to understand how respondents comprehend the response options in the two languages. PMID- 17288069 TI - Budget impact of Medicaid Section 1115 demonstrations for early HIV treatment. AB - A state-transition model of HIV disease was used to project the costs to Medicaid, Medicare, and AIDS Drug Assistance Programs of proposed Section 1115 Medicaid demonstration projects for the early treatment of HIV-infected patients in Georgia and Massachusetts. Neither demonstration project was projected to meet 5-year tests of no increase in Federal spending and in both States average patient costs to all payers were highest in the first year after enrollment. In assessing expanded health care access for patients with chronic diseases, government payers should consider overall budgetary effects and separately analyze costs for each year's enrollees to avoid creating incentives to cap enrollments. PMID- 17288070 TI - Low-income children's preventive services use: implications of parents' Medicaid status. AB - This article examines the effect of parents' Medicaid status on the use of preventive health services by young children. Using data from the 1996 Medical Expenditure Panel Survey (MEPS), we analyzed a logit model for receipt of any well-child visits (WCVs) that compared three groups of low-income children. The three groups, defined by the joint insurance status of children and their parents, involved Medicaid pairs (both the child and the parent had Medicaid throughout the year), mixed pairs (the child had Medicaid and the parent was uninsured), and uninsured pairs (both child and parent were uninsured). Medicaid coverage for children was positively associated with receipt of any WCVs. However, the utilization effect of Medicaid coverage for children was significantly larger when the parent was also on Medicaid instead of being uninsured. Considering uninsured children with uninsured parents in 1996, enrolling only the children in Medicaid would have increased the percentage with WCVs from 29 to 43 percent according to simulations with the logit model. If the parents were enrolled in Medicaid as well, the percentage of children with any WCVs would have increased to 67 percent. PMID- 17288071 TI - Children's service use during the transition to PCCM in two states. AB - This study examines whether use of primary, preventive, or emergency care changed as primary care case management (PCCM) programs for children were implemented in Alabama and Georgia. Using claims data we track the same children over time, and control for geographic availability of Medicaid providers, which also changed over this period. A decline in use of all three types of care was found to be associated with PCCM implementation, with use of primary and preventive care falling below national averages and recommended use rates. Family difficulties in shifting to exclusive use of unfamiliar providers is the primary reason for the decline in use rates. PMID- 17288072 TI - 2003 Medicaid versus commercial beneficiary experience with care. PMID- 17288073 TI - U.S. and German case studies in chronic care management: an overview. AB - In December 2004, the Bertelsmann Stiftung, The Commonwealth Fund, and AcademyHealth jointly sponsored a conference in Berlin, Germany on "Case Studies in Chronic Care Management." This conference assembled representatives from the U.S. and German Governments, several organizations that had developed chronic care management initiatives in the two countries, and other health care and policy experts to discuss clinical, organizational, and financing issues. The case studies discussed at the conference are presented in this issue of the Review; this article describes some relevant considerations that are common to the U.S. and German health systems. PMID- 17288074 TI - Care management in Germany and the U.S.: an expanded laboratory. AB - Germany and the U.S. share a keen interest in exploring the potential of care management programs for the chronically ill. Despite obvious health system differences, in both countries there has been a proliferation of disease management models, initiated by a variety of actors, paid for in different ways, targeting different types of population groups, and encompassing a broad menu of interventions and services. Comparison of three case studies from the U.S. and four from Germany reveals greater differences among models within countries than between them. PMID- 17288075 TI - Physician involvement in disease management as part of the CCM. AB - Phase I of the voluntary chronic care improvement (CCI-I) under traditional fee for-service Medicare initiative seeks to extend the benefits of disease management to an elderly population with comorbid chronic medical conditions. Active, sustained involvement of treating physicians, a historical deficit of disease management programs, is a CCI-I program goal. During the last decade, Kaiser Permanente, an integrated health care delivery system with more than 60 years of experience in managing the care of individuals and populations, has applied the chronic care model (CCM) to develop care management strategies for populations of patients with chronic medical conditions. Physician leadership and involvement have been key to successfully incorporating these practices into care. The scope of physician involvement in leading, developing, and delivering chronic illness care management at Kaiser Permanente is described as a basis for identifying opportunities to involve practicing physicians in the CCI-I. PMID- 17288076 TI - Managing chronic conditions for elderly adults: the VNS CHOICE model. AB - Chronic illness combined with functional impairment often results in an increased need for medical care and supportive long-term care (LTC) services. Navigating the health care system is challenging and complex, and even more so for patients with complex needs. Traditional fee-for-service care does not support and facilitate coordination and collaboration between providers and service settings. In New York State, managed LTC, a model of coordinated care for the chronically ill, endeavors to provide a bridge between primary, acute, home and community based, and institutional LTC services for a medically complex and functionally frail nursing home eligible population. PMID- 17288077 TI - Case study of American Healthways' diabetes disease management program. AB - Disease management has been defined as a system of coordinated health care interventions and communications for populations with conditions in which patient self-care efforts are significant (Disease Management Association of America, 2005). The purpose of this article is to provide an overview of the diabetes disease management program offered by American Healthways (AMHC) and highlight recently reported results of this program (Villagra, 2004a; Espinet et al., 2005). PMID- 17288078 TI - Continuous case management of a German statutory health insurance. AB - To support insured patients, especially those with chronic illnesses or disabilities, the German statutory health insurance Techniker Krankenkasse (TK) offers continuous case management (CCM) under a rehabilitation advisory program serving more than 150,000 insurees each year Rehabilitation advisors provide individual counseling, generally by telephone. They inform patients about treatment and rehabilitation options, about health care providers, and about other TK services. In a key feature, the model coordinates care across different health care sectors. Through the CCM approach, TK not only assures the best possible care for its insurees, but also safeguards its long-term financial sustainability. PMID- 17288079 TI - First German disease management program for breast cancer. AB - The first disease management program contract for breast cancer in Germany was signed in 2002 between the Association of Regional of Physicians in North-Rhine and the statutory health insurance companies in Rhineland. At the heart of this unique breast cancer disease management program is a patient-centered network of health care professionals. The program's main objectives are: (1) to improve the quality of treatment and post-operative care for breast cancer patients, (2) to provide timely information and consultation empowering the patient to participate in decisionmaking, (3) to improve the interface between inpatient and outpatient care, and (4) to increase the number of breast-conserving surgeries. PMID- 17288080 TI - Germany's disease management program: improving outcomes in congestive heart failure. AB - Hospital admissions among patients with congestive heart failure (CHF) are a major contributor to health care costs. A comprehensive disease management program for CHF was developed for private and statutory health insurance companies in order to improve health outcomes and reduce rehospitalization rates and costs. The program comprises care calls, written training material, telemetric monitoring, and health reports. Currently, 909 members from six insurance companies are enrolled. Routine evaluation, based on medical data warehouse software, demonstrates benefits in terms of improved health outcomes and processes of care. Economical evaluation of claims data indicates significant cost savings in a pre/post study design. PMID- 17288081 TI - PRO DEM: a community-based approach to care for dementia. AB - Physicians in a region south of Bremen, Germany, created PRO DEM (for patients with dementia), a service coordinating medical care and social intervention for patients with dementia. The program now serves about 125 outpatients and their families, along with 360 patients in nursing homes. Two nurse consultants coordinate patient care. Treatment strategies are decided during a multidisciplinary case conference among physicians, nurses, and other professionals. Social intervention modules include various care groups for patients and respite services for caregivers. PRO DEM aims to provide fully coordinated care for a better quality of life for patients and caregivers, delaying nursing home admission as long as possible. PMID- 17288082 TI - The safety and efficacy of a new adjustable plate used for proximal tibial opening wedge osteotomy in the treatment of unicompartmental knee osteoarthrosis. AB - Twenty opening wedge tibial osteotomies were performed using the Osteotrac plate, which consists of a two-piece plate with a one-way ratcheting mechanism with two degrees of freedom. A variety of concomitant procedures were performed including osteochondral transfer, tibial tubercle medialization, and anterior cruciate ligament reconstruction. The change in tibiofemoral alignment in the coronal plane and the shift in lower extremity mechanical axis were determined. The average lateral shift in the lower extremity mechanical axis was 24% of the tibial plateau width. The average change in the mechanical tibiofemoral angle was 7 degrees of valgus. Union rate at the osteotomy site was 95%. No deep infections, clinical deep venous thrombosis, or device failures occurred. The Osteotrac plate provides safe and effective fixation and intraoperative adjustability to achieve and maintain a lateral shift of the lower extremity mechanical axis and valgus correction of the tibiofemoral alignment in patients with varus knees undergoing proximal tibial opening wedge osteotomy and associated meniscal and chondral procedures. PMID- 17288083 TI - Histologic appearance of "pristine" articular cartilage in knees with unicompartmental osteoarthritis. AB - This prospective study evaluated the histologic appearance of the "unaffected" lateral compartment articular cartilage in 15 knees with medial compartment degenerative arthritis undergoing unicompartmental arthroplasty or total knee arthroplasty between the ages of 54 and 65 years. The biopsy specimens were compared to a control group of patients between the ages of 25 and 45 years who were having routine arthroscopic meniscectomy. These patients had an intercondylar notch biopsy at the time of their arthroscopic procedure. A decrease in proteoglycan, breakdown of calcification, clonal grouping of chondrocytes, and/or hypocellularity was noted in the biopsy specimens of the "pristine" appearing lateral compartment in patients with isolated medial compartment disease indicative of progressive osteoarthritis. PMID- 17288084 TI - Influence of joint area design on tibial component migration: comparison among a fixed symmetrical, asymmetrical, and moveable bearing. AB - Fifty-four knees (50 patients) were allocated to three different tibial polyethylene inserts (standard/rotating platform/FS1000) in the Freeman-Samuelson (Finsbury Orthopaedics Ltd, Surrey, United Kingdom) total knee arthroplasty. The FS1000 design has a spherical medial and a roller-in-trough configuration laterally. Radiostereometric examinations were done postoperatively and after 3, 12, and 24 months. The median migration of the metal-backing and the Hospital for Special Surgery scores did not differ between the three groups. At 2 years, the median external/ internal displacements for the rotating platforms were 2.8 degrees and 0.2 degrees, respectively (rotating platforms versus standard inserts/rotating platforms versus FS1000: P < .0005). Longitudinal rotations above the detection limits for radiostereometry were observed in some of the fixed implants (standard and FS1000 designs), indicating conditions for backside wear. PMID- 17288085 TI - Late hematogenous infections after total knee arthroplasty: experience with 3013 consecutive total knees. AB - Newer technologies have seen a gradual decline in mechanical causes for total knee arthroplasty (TKA) failures. As these mechanical mechanisms of failure have slowly diminished, infections have come to comprise an even larger proportion of complications in knee replacement surgery. This article presents a retrospective review of a single surgeon's incidence of late hematogenous infections after 3013 consecutive primary TKAs using a standard surgical technique. Fifteen late hematogenous infections were found in 14 (0.5%) patients at an average of 10 years postoperatively. The surgical protocol is reported and the late infections are analyzed for their etiologies and outcomes. PMID- 17288086 TI - Diagnosis and treatment of postarthroscopic synovial knee fistulae: a report of four cases and review of the literature. AB - Development of synovial knee fistulae following arthroscopic knee surgery is a rare but under-reported complication. The diagnosis and treatment of this complication is described in a series of four patients. Synovial knee fistula formation is a benign complication and in the majority of patients it can be treated conservatively with immobilization until healing occurs. The presence of infection should always be excluded. PMID- 17288087 TI - Integration of arthroscopic and C-arm imaging into the arthroscopic image management system: technical note. PMID- 17288088 TI - Periprosthetic pseudo-osteolysis and total knee arthroplasty: case report. PMID- 17288089 TI - Pigmented villonodular synovitis of the pes anserine bursa: case report. PMID- 17288090 TI - Locking plate technology: current concepts. AB - The management of fractures with traditional plating techniques has undergone a paradigm shift over the past 20 years. For many fractures, anatomic reduction using a dynamic compression plate has been the gold standard. However, minimally invasive approaches combined with biologically friendly internal fixation have become accepted methods of complex fracture treatment. The orthopedic literature has demonstrated advantages when comparing locking plate techniques with traditional compression plating techniques, particularly in fractures about the knee. The advantages of locking plates apply most directly to cases of highly comminuted fractures, unstable metadiaphyseal segments, and osteoporotic fractures. The biomechanical properties of locking plates have distinguished and defined their clinical use compared to traditional plates. A thorough understanding of these properties will assist the orthopedic surgeon in choosing the appropriate construct when faced with a difficult fracture. Compression plating requires absolute stability for bone healing. In contrast, locking plates function as "internal fixators" with multiple anchor points. This type of fixed angle device converts axial loads across the bone to compressive forces across fracture sites, minimizing gap length and strain. The strain theory demonstrates that anatomic reduction is not required for bone healing, and that tolerable strain (2%-10%) can promote secondary bone healing. Callus formation is further promoted when biologically friendly surgical approaches are combined with locking plate "internal fixators". In contrast, conventional plates function by creating an environment where primary bone healing occurs. This plate provides "absolute rigidity" and requires anatomic reduction fixed in compression. Primary bone healing occurs in this manner. In highly comminuted, segmentally deficient, or porotic bone, bone quality is poor and "absolute rigidity" does not exist. Furthermore, soft-tissue stripping adds a biologic insult to the poor bone quality. These disadvantages may lead to poor outcomes such as nonunion, implant failure, malunion, or even infection. These disadvantages remain theoretical, as no prospective studies clearly demonstrate a difference between plating methods in difficult metadiaphyseal or osteoporotic fractures. However, the overwhelming biomechanical evidence has led to a more biologically friendly approach to these fractures. The indications for use of locking plates are evolving. The literature demonstrates low rates of nonunion and overall complication rates with locking plates in difficult metaphyseal and diaphyseal fractures. Anatomic reduction of the articular surface remains paramount. Hybrid techniques that combine the benefits of compression plate fixation with the biological and biomechanical advantages of locking plates are the most likely end result of current locking plate applications. PMID- 17288091 TI - Distal femoral fractures. AB - Distal femoral fractures largely occur secondary to high-energy trauma in the younger population and as osteoporotic fractures in the elderly population, including periprosthetic fractures above a TKA. Attempts to gain satisfactory axial alignment, articular congruity, and knee range of motion with conservative treatment have been largely disappointing. Operative fixation options include open reduction and internal fixation, intramedullary nailing, and bridge plating or percutaneous submuscular plating techniques. As with any fracture, treatment choice must be individualized according to the nature of the injury, bone quality, and patient demand. Regardless of treatment method, goals include restoration of articular congruity, anatomical length, rotation, and axial alignment while establishing adequate fixation to initiate early and unrestricted range of motion. PMID- 17288092 TI - Complex fractures of the tibial plateau. PMID- 17288094 TI - New-age wound care solutions drive improved efficiency, outcomes, and patient satisfaction. PMID- 17288093 TI - Management of complications associated with fractures around the knee. PMID- 17288095 TI - Opportunities for improvement abound in the care of obstructive lung diseases. AB - There is ample room for improvement in COPD care. New research confirms that serious gaps remain in the care of patients with obstructive lung diseases such as COPD. However, experts believe that system-level interventions can go a long way toward correcting the problem. And they have identified some key areas to target for quality improvement. PMID- 17288096 TI - New approaches and unique partnerships take on childhood obesity. AB - Health plans, states, and DM vendors get serious about childhood obesity. Armed with data showing that inaction will be costly indeed, health plans are beginning to formulate comprehensive approaches to childhood obesity. Further, the state of Arkansas is making the issue a top priority with the help of DM vendors and other partners. PMID- 17288097 TI - Noninvasive approach to diabetes screening and monitoring shows promise. AB - Noninvasive screening device offers intriguing possibilities in diagnosing diabetes. Huge numbers of diabetics remain undiagnosed, and part of the problem is the fact that current screening methodologies are invasive and inconvenient. However, one potential new screening option has neither of those drawbacks, and early indications show that it is sensitive enough to even pick up prediabetes. PMID- 17288098 TI - Injury prevention and performance enhancement: a training program for basketball. AB - The purpose of this investigation was to determine the effectiveness of a training program for basketball. Effectiveness in this case was determined by the program's ability to decrease the rate of injury and to increase athletic performance on the basketball court. The search for a program to help prevent serious knee ligament injuries has resulted in a plyometric type of training program. The first stage began eight weeks before basketball season, the second three days before the season started. Upon completion of the second testing session, both male and female participants had improved in all tests administered. This shows that a supervised, scientifically developed program consisting of sports-specific material can result in an increase in sports performance. There were no injuries reported during the training period or during the season lending credence to the fact that a program of this type can result in injury reduction. PMID- 17288099 TI - Newborn screening coupled with comprehensive follow-up reduced early mortality of sickle cell disease in Connecticut. AB - To assess the impact of newborn screening (NBS) on the mortality of children with sickle cell anemia, we analyzed the Connecticut death certificates of all children less than 15 years old at death. We compared sickle cell-related deaths in three periods: 1970-1988 when there was no state NBS; between 1988 and 1990 when there was limited state NBS; and 1990-2002 when universal NBS was in effect in Connecticut. In the period 1988-2002, we identified all death certificate records in which sickle cell anemia was listed as a cause of death and compared these with children who were shown to have sickle cell anemia (Hb SS and sickle beta(o) thalassemia) by the state's NBS programs. In the 11-1/2 years after universal NBS was initiated in Connecticut in 1990, there were no reported deaths among infants diagnosed at birth with Hb SS or sickle-beta(o) thalassemia. In the 18 years before any State NBS (1970-1988) there were 13 deaths attributed to sickle cell diseases. The limited State NBS program conducted between 1988 and July 2000 missed testing five affected children who subsequently died. These results document a marked reduction in mortality since the introduction of NBS for hemoglobinopathies and suggest that the Connecticut NBS program, coupled with comprehensive follow-up care, greatly reduced mortality. PMID- 17288100 TI - Lung abscess in a patient with Kartagener syndrome. PMID- 17288101 TI - A comparison of different protease inhibitors on coronary heart disease risk. PMID- 17288103 TI - Whipple's disease redux. AB - Whipple's disease is an uncommon, multisystem disease that typically strikes middle-aged men causing abdominal pain, arthralgia and malabsorption. The characteristic patholological finding is infiltration of the small intestinal mucosa and accompanying lymph nodes with PAS positive macrophages. Similar histological findings can be found in other involved organs. Tropheryma whippleii, the causative organism, usually responds to antibiotic therapy. Polymerase chain reaction is used to confirm the diagnosis. This report summarizes, arguably, Connecticut's first documented case 50 years ago, and the saga of establishing its diagnosis and the subsequent attempt to publish it. PMID- 17288104 TI - The state of physician office-based health information technology in Connecticut: current use, barriers and future plans. AB - Qualidigm and the Connecticut State Medical Society-Independent Practice Association (CSMS-IPA), Inc. have conducted a survey of the physicians participating in the CSMS-IPA to assess current use of health information technology in their offices and their plans for future use. The survey was conducted to assist eHealth Connecticut, a Connecticut-based nonprofit organization, in its charge to promote electronic health information exchange in Connecticut. The survey was distributed to 2,366 medical offices representing 6,956 physicians in Connecticut. Survey results revealed that the most commonly utilized types of technology were practice management systems (70%) and e-mail (64%). The most common barriers to the adoption of new technologies were cost (71%) and time requirements (39%). Primary-care providers and small practices were more likely to cite cost as a barrier to technology implementation. Despite these challenges, many physicians reported plans to implement electronic medical records (25%) or electronic prescribing (20%) in the next year. PMID- 17288105 TI - Mindfulness meditation and public health. PMID- 17288106 TI - The diagnosis and treatment of some of the more common diseases of the knee joint. 1907. PMID- 17288107 TI - Epidemiology of accidental deaths among college students. 1957. PMID- 17288108 TI - Medicine in a changing world. 1957. PMID- 17288109 TI - A "perfect storm". PMID- 17288110 TI - Improving diabetes therapy through performance feedback and educational outreach. PMID- 17288111 TI - ABFM's recertification examination. PMID- 17288112 TI - Interview with Stuart H. Altman, Ph.D., HFACHE, dean and professor, The Heller School, Brandeis University. Interview by Kyle L. Grazier. PMID- 17288113 TI - The future of healthcare technology. PMID- 17288114 TI - Practical issues in the design and implementation of pay-for-quality programs. AB - Health plans, healthcare purchasers, and provider organizations throughout the United States are crafting pay-for-performance programs with the intent of improving the quality of care and with recognition of the need to restrain rapidly rising costs. Health plans and large, self-insured employers have typically led the movement toward using quality scorecards with which to gauge hospital and physician performance, coupled with the use of financial incentives directed at hospitals, physician group practices, and individual physicians and practice teams. In this article we provide a conceptual perspective for understanding the objectives and constraints of payers and providers as they wrestle with the next generation of pay-for-quality (P4Q) programs. We identify a set of practical issues that must be addressed in developing and conducting P4Q programs in different market environments. Those issues include specific strategies for choosing quality metrics, units of accountability, size of incentive, data and measurement systems, payout formulas, and collaboration among payers. We illuminate these issues by considering different approaches in light of real-world P4Q demonstrations underway in the Rewarding Results program, in Bridges to Excellence program, and in specific provider organizations we interviewed over the years. The discussion of practical issues highlights principles and examples directly relevant to hospitals and physician organizations that are considering participation in P4Q as well as to those reexamining their physician compensation mechanisms. PMID- 17288115 TI - A comparative performance scorecard for federally funded community health centers in North Carolina. AB - To make informed management decisions, healthcare executives must have timely and useful information about the performance of their organizations. A review of the methods used by the Health Resources and Services Administration's Bureau of Primary Health Care to evaluate the performance of community health centers (CHCs) revealed a lack of such information. This information gap motivated the development of a comparative performance scorecard for the federally funded CHCs in North Carolina. The scorecard includes 19 indicators in four performance dimensions (access to care, financial performance, human resources, and utilization and productivity). A survey of participating CHC executive directors showed that the comparative performance scorecard is a useful tool for managing and evaluating the performance of CHCs. PMID- 17288116 TI - Hospital administration in the early 1900s: visions for the future and the reality of daily practice. AB - This article explores the first vision of modern hospital management as it was advanced by the American Hospital Association in the early 1900s and compares it with the reality of daily practice at the time. The findings show a wide gap between vision and reality. They also show that many of the issues faced by hospital administrators a hundred years ago remain relevant today. They include the tension between adoption of new technology and the cost of hospital care, advocacy for business practices from the private sector, and the administrator's responsibility in the area of quality of care. PMID- 17288117 TI - The performance management system: applying and evaluating a pay-for-performance initiative. AB - The clinical operations and programs division at the University of Texas M. D. Anderson Cancer Center undertook an initiative, as part of a new performance management system, to determine the effectiveness in aligning individual performance goals to institutional goals and linking performance to rewards (i.e., distinguishing high performers from low performers). The initiative was completed in two phases--the first involved a pilot group of administrators and managers, and the second encompassed the entire clinical area of the institution. Progress was monitored using a survey specific to the performance management initiative, an institutional employee opinion survey, and employee performance review and merit data. We demonstrated support for both goals in the findings from our performance management survey and for our second goal with the institutional employee opinion survey results. Our correlation analysis of the linkage between performance and merit data provided further evidence that the initiative's implementation affected our goal of better distinguishing high performers from low performers. Although our results indicate that we made significant progress toward meeting our goals, we outlined limitations and implications of our results for other organizations to consider as they embark on their own performance management initiatives. Thinking of performance management as a complete system that encompasses goal alignment, education, communication, and continuous feedback can lead to the recognition of top performers. This recognition is important as organizations try to retain their top talent and improve the performance of all employees in an effort to positively influence the patient experience. PMID- 17288118 TI - A cultural diversity assessment and the path to Magnet status. AB - Magnet hospitals understand that healthcare providers no longer work with a homogeneous stakeholder population (including healthcare professionals, employees, and patients); thus, organizations must ensure that their practices accommodate the patients and employees of today and tomorrow. Although the medical center did not pursue its Magnet status goal, it is on the path to transforming its culture into a culturally competent environment. Such an environment allows the organization to be better poised for success when the time is right to, once again, pursue Magnet designation. PMID- 17288119 TI - Review of mortality and cardiovascular event rates in patients enrolled in clinical trials for claudication therapies. AB - Pharmacological and non-pharmacological interventions to improve function and quality of life in patients with claudication are being evaluated in clinical research trials. An important component of clinical development programs is assessing the safety of the intervention and monitoring for adverse impact of the therapy on research participants. The conduct of both of these safety assessments is facilitated by the ability to estimate the anticipated rates of cardiovascular events and death in the target population. To obtain estimates of these rates, data were abstracted from randomized, double-blind, placebo-controlled trials performed in patients with claudication and designed to show functional improvement, and which have been published since 1990. Patient-year exposures and the number of deaths, serious adverse events and cardiovascular serious adverse events in the placebo arms of these trials were tabulated, and summed event rates calculated. The mortality rate was 1.9 deaths per hundred patient-years (27 deaths observed in 1446 patient-years). The mortality rate in claudication trials is lower than that reported in natural history studies. Cardiovascular serious adverse events in claudication trials were observed at a rate of 8.5 per hundred patient-years (65 events in 762 patient-years). Thus, cardiovascular morbidity and mortality should be expected in clinical trials enrolling claudicants. The current analyses provide benchmark data for ensuring that development programs are large enough to allow meaningful safety conclusions, and to assist in data and safety monitoring of these trials. PMID- 17288120 TI - Functional status measured by walking impairment questionnaire and cardiovascular risk prediction in peripheral arterial disease: results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study. AB - The prognostic impact of the functional status of patients with intermittent claudication is still obscure. From the lists of seven general practitioners, we identified all subjects aged 40-80 years (n = 4352). Of those reporting leg symptoms while walking on the Rose questionnaire (n = 760), 60 had a qualifying diagnosis of peripheral arterial disease (PAD). All of them received the Walking Impairment Questionnaire (WIQ). For each patient affected by PAD, three sex- and age-matched controls were selected randomly. After a 24-month follow-up, survival curves showed that PAD patients with WIQ scores > median had a higher cardiovascular risk than controls, and patients with WIQ scores < median had an even poorer prognosis (p < 0.001 for all WIQ domains). In PAD, after adjustment for age, sex, ankle-brachial index and comorbidity, two WIQ domains (ie walking speed and stair-climbing) were associated with cardiovascular events. The cardiovascular risk of claudicants who had a score > median for at least three WIQ domains was intermediate versus the risk of controls and PAD patients with a WIQ score < median, also when adjusted for the covariates indicated above (RR = 3.26, p = 0.019). In intermittent claudication, a worse functional status entails a greater risk of ischemic events versus low functional impairment. PMID- 17288121 TI - Limb hemodynamics are not predictive of functional capacity in patients with PAD. AB - To the practicing clinician, it seems obvious that limb hemodynamics would be the primary determinant of walking distance. However, other determinants, such as skeletal muscle metabolism, may play a role. Accordingly, in the current study, we examined the relationship between measures of limb hemodynamics and walking capacity in patients with peripheral arterial disease (PAD). We measured toe and ankle pressures for calculation of toe- (TBI) and ankle (ABI)-brachial indices; basal and hyperemic calf blood flow (CBF; by plethysmography); and initial (ICT) and absolute (ACT) claudication time using the Skinner-Gardner protocol. As expected, PAD patients had impaired limb hemodynamics with reduced TBI, ABI and a reduction in ABI post-exercise. However, there was no relationship between any of the hemodynamic variables (including ABI, ABI reduction post-exercise, TBI, baseline or maximal CBF) and walking distance as assessed by ICT or ACT. A subset of PAD patients with an ACT >750s (n = 16; 'long claudicators') were compared with a subset of PAD patients with an ACT <260s (n = 16; 'short claudicators'). The average ACT in the long claudicants was over fivefold greater than the short claudicators. Surprisingly, there were no differences between the two groups in any of the hemodynamic variables. There was also no relationship between the initial ABI, TBI, toe pressure, baseline or hyperemic CBF, and the improvement in ACT over the 3-month course of the study. This study found little relationship between hemodynamic variables and functional capacity in PAD. Accordingly, to assess the response to therapeutic interventions, exercise performance and functional status need to be directly measured, and cannot be predicted from hemodynamic measurements. PMID- 17288122 TI - Acute right lower extremity iliofemoral deep venous thrombosis secondary to an anomalous inferior vena cava: a report of two cases. AB - A congenital anomaly of the inferior vena cava is an increasingly identified risk factor for iliocaval deep venous thrombosis in young patients. We present two cases of acute right lower extremity iliofemoral deep venous thrombosis in 16 and 18-year-old patients that were ultimately diagnosed with an underlying anomalous iliocaval venous system. In one patient, the inferior vena cava was congenitally absent and the right iliac vein was diffusely stenotic with a proximally located high-grade stricture. In the other subject, the infrarenal inferior vena cava and right iliac vein were diffusely hypoplastic. Compensatory venous flow in both subjects was via large perilumbar venous collateral veins and a prominent azygous system. Both patients were successfully treated with a combination of initial catheter-directed thrombolysis followed by balloon angioplasty and venous stent placement. PMID- 17288123 TI - Images in vascular medicine. Pseudoaneurysm as a result of peripheral arterial stent infection. PMID- 17288124 TI - Images in vascular medicine. Cross-clamp injury: an unusual cause of intermittent claudication. PMID- 17288125 TI - Images in vascular medicine. Mirror image artifact. PMID- 17288126 TI - SVMB presidential address. The time has come for vascular medicine. PMID- 17288128 TI - American society of echocardiography report. Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology. AB - Noninvasive measures of atherosclerosis have emerged as adjuncts to standard cardiovascular disease (CVD) risk factors in an attempt to refine risk stratification and the need for more aggressive preventive strategies. Two such approaches, carotid artery imaging and brachial artery reactivity testing (BART), are ultrasound based. Numerous carotid artery imaging protocols have been used, and methodologic aspects are described in detail in this review. The panel recommends that protocols: (1) use end-diastolic (minimum dimension) images for intimal-medial thickness (IMT) measurements; (2) provide separate categorization of plaque presence and IMT; (3) avoid use of a single upper limit of normal for IMT because the measure varies with age, sex, and race; and (4) incorporate lumen measurement, particularly when serial measurements are performed to account for changes in distending pressure. Protocols may vary in the number of segments wherein IMT is measured, whether near wall is measured in addition to far wall, and whether IMT measurements are derived from B-mode or M-mode images, depending on the application. BART is a technique that requires meticulous attention to patient preparation and methodologic detail. Its application is substantially more challenging than is carotid imaging and remains largely a research technique that is not readily translated into routine clinical practice. PMID- 17288127 TI - Guidelines for noninvasive vascular laboratory testing: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology. AB - Accompanying the rapid growth of interest in percutaneous vascular interventions, there has been increasing interest among cardiologists in performing noninvasive vascular testing using ultrasound. In an attempt to provide recommendations on the best practices in vascular laboratory testing, this report has been prepared by a writing group from the American Society of Echocardiography (ASE) and the Society for Vascular Medicine and Biology. The document summarizes principles integral to vascular duplex ultrasound--including color Doppler, spectral Doppler waveform analysis, power Doppler, and the use of contrast. Appropriate indications and interpretation of carotid artery, renal artery, abdominal aorta, and peripheral artery ultrasound imaging are described. A dedicated section summarizes noninvasive techniques for physiologic vascular testing of the lower extremity arteries--including measurement of segmental pressures and pulse volume plethysmography. The use of exercise testing in the evaluation of peripheral artery disease, ultrasound evaluation of the lower extremities after percutaneous revascularization, and the diagnosis and management of iatrogenic pseudoaneurysm (PSA) is also discussed. A section on the important topic of vascular laboratory accreditation is included. Finally, additional details regarding proper technique for performance of the various vascular tests and procedures are included in the Appendix. PMID- 17288129 TI - [Strategy of quality control for traditional Chinese medicines and chromatographic technology]. AB - The application of chromatography, a modern technology for highly efficient separation and analysis in the research of therapeutic basis matter and quality control of traditional chinese medicine (TCM), is summarized. A new strategy with metabonomics is put forward to achieve integral study on therapeutic basis matter and action mechanism of TCM, and to reveal and control the comprehensive quality of TCM. Modern chromatography and hyphenated techniques are one of the important technique platforms in quality control of TCM. PMID- 17288130 TI - [Application of liposomes in liquid chromatography and capillary electrophoresis]. AB - Liposome has similar lipid bilayer structure and fluid characteristics to real cell membrane, and plays an important role in mimetic biomembrane research. The preparation and characterization of liposome, studies on drug-liposome partitioning and protein-liposome interaction with immobilized liposome chromatography, application of liposome on drug separation, protein separation and protein interaction by capillary electrophoresis are reviewed. PMID- 17288132 TI - [Enrichment of nicotine in plasma with three-phase hollow fiber based liquid phase microextraction]. AB - A novel method for fast determination of nicotine in plasma was established by using high performance liquid chromatography (HPLC) coupled with a three-phase hollow fiber based liquid phase microextraction (TP-HF-LPME) technique for sample preparation. The microextraction was mediated by the pH difference between the environment inside and outside of an organic phase immobilized in the pores formed in the wall of a polypropylene hollow fiber. The pH value of the medium outside the organic phase was adjusted by adding a dilute KOH solution to form a basic donor phase while the pH value of the inner media was set to pH 3 to form an acceptor phase using a 10 mmol/L KH2PO4 solution. On working conditions, neutral nicotine molecules were firstly extracted from the original sample solution to the organic phase, and then the analyte was extracted from the organic phase to the acceptor phase. After described extraction time, 4 microL of acceptor phase was withdrawn and directly injected into HPLC system for analysis. Parameters related to TP-HF-LPME (organic solvent, pH of acceptor and donor phase, stirring rate, salt effect, methanol content in acceptor phase and extraction time) were also optimized experimentally. The proposed method integrates extraction, enrichment and clean-up into a single step, dramatically simplifying the traditional procedure to prepare a liquid sample with complex matrices such as plasma. It has been demonstrated to be a very fast, effective and virtually "green" sample preparation technique, which provided a good linear range (0.1 - 50 mg/L) with Nu of 0.999 6, a low detection limit (0.05 mg/L, S/N = 3) and a satisfactory relative standard deviation (< 5%). PMID- 17288131 TI - [Application of molecularly imprinted solid phase extraction in the assay of environmental samples]. AB - Molecularly imprinted polymers (MIPs) have already appeared as new selective sorbents for solid phase extraction (SPE) of organic compounds in different samples by extracting certain analytes selectively from complex matrices without matrix interference. This review aims to present a summary of the application of MIPs in the solid phase extraction and enrichment of analytes from the environmental samples. The target analytes include pesticides, herbicides, toxins, veterinary drugs, heavy metal ions, endocrine disruptor compounds and other environmental hazards. PMID- 17288133 TI - [Study on the retention behaviors and analytical methods of polysaccharides from Duanaliella salina by high performance size-exclusion chromatography]. AB - There are many polysaccharides with biological activities including anti-virus and anti-tumor in the residue produced by the extraction of beta-carotene from Duanaliella salina. In this paper, a method of high performance size-exclusion chromatography coupled with refractive index detection has been developed for the relative molecular mass analysis of the polysaccharides isolated from the residue. The effects of salt and pH values of mobile phase on retention behaviors of five polysaccharides fractions were investigated on two HPSEC columns (Waters Ultrahydragel Linear, 7.8 mm i. d. x 300 mm) connected in series. The results showed that 0. 1 mol/L NaAc buffer solution may be utilized as mobile phase during HPSEC under the conditions of column temperature of 45 degrees C and flow rate of 0.9 mL/min to minimize nonspecific interaction of sulfated polysaccharides fraction (PD4a), complex carbohydrate containing oligonucleic acid (PD4b) and acidic polysaccharide fraction (PD1) with the column matrix. In addition, under the conditions the association effect of the polysaccharide molecules was eliminated. Thereby, the polysaccharide molecules were eluted and separated following equilibrium exclusion mechanism mainly. The weight mean molecular masses (M(w)) of five polysaccharide fractions from D. salina determined under optimum chromatographic conditions were 1 548 000 for PD1, 33 000 for PD2, 67 000 for PD3, 424 000 for PD4a and 10 000 for PD4b. For sulfated polysaccharide fraction PD4a, the relative standard deviations were 1.7% and 0.88% for M(w) and peak area, respectively. PMID- 17288134 TI - [Determination of chlorhexidine acetate in chlorhexidine acetate suppositories by high performance liquid chromatography coupled with hollow fiber membrane solvent microextraction]. AB - A novel method was developed to determine the content of chlorhexidine acetate (CA) in chlorhexidine acetate suppositories by high performance liquid chromatography (HPLC) coupled with hollow fiber membrane solvent microextraction. The sample was extracted with 1.5 mol/L acetic acid solution five times, then a hollow fiber containing n-octanol was placed in the sample solution to perform microextraction for extracting 20 min. The extract was analyzed by HPLC with UV detection at 260 nm. The chromatographic conditions were as following: acetonitrile-redistilled water (29:71, v/v, containing 0.3% triethylamine, pH 3.0) as mobile phase with the flow rate of 1 mL/min. The calibration curve of CA was linear from 0.5 to 16 mg/L. The method recovery was over 98.0% with relative standard deviation less than 4.0%. By using hollow fiber membrane solvent microextraction, the enrichment of 24-fold was achieved. The method is specific, simple, fast, sensitive and suitable for the determination of chlorhexidine acetate. PMID- 17288135 TI - [Separation of isomeric compounds by high speed countercurrent chromatography]. AB - High speed countercurrent chromatography (HSCCC) was successfully used for the separation and preparation of isomeric compounds. The influence of various two phase solvent systems on the resolution of the natural catechin isomers of (-) epigallocatechin gallate (EGCG) and (-) -gallocatechin gallate (GCG) from green tea polyphenols and the synthetic isomeric compounds of para-, ortho-, meta bromoanilline was investigated. The results indicated that the catechin isomers of (-) -EGCG and (-) -GCG can be isolated through two runs of preparative HSCCC with two-phase solvent system composed of n-hexane-ethyl acetate-water (1: 10: 10 in volume ratio). The upper organic phase was used as stationary phase and the lower aqueous phase as mobile phase, while the mobile phase was operated at a flow rate of 3.5 mL/min, and the apparatus rotated at 800 r/min. High performance liquid chromatographic analysis of (-) -EGCG and (-) -GCG revealed that the purity was all over 98%. The isomeric compounds of para-, ortho-, meta bromoaniline can also be effectively isolated through a single run of preparative HSCCC with the mobile phase flow rate of 3.0 mL/min and the apparatus rotation speed of 800 r/min by using tetrachloromethane-chloroform-methanol-water (7: 3: 7: 3 in volume ratio) as two-phase solvent system, while the lower phase was selected as stationary phase and the upper phase as mobile phase. PMID- 17288136 TI - [Resolution of racemic 1, 1'-bi-2-naphthol and its derivatives by molecularly imprinted polymers]. AB - 1, 1'-Bi-2-naphthol is one of the most popular analytes in chiral separation since optically active 1,1'-bi-2-naphthol and its derivatives are frequently used as chiral auxiliaries and ligands in asymmetric synthesis. Therefore, it was employed as template for the preparation of molecularly imprinted polymer (MIP) which was used as liquid chromatographic stationary phase. In this study, the MIP was prepared by bulk polymerization using (R)-(+)-1 , 1'-bi-2-naphthol as template molecule, 4-vinyl pyridine, ethylene glycol dimethacrylate and acetonitrile as functional monomer, cross-linker and porogen respectively. High performance liquid chromatography (HPLC) was employed to study the chiral recognition properties of the resulting MIP. The effect of chromatographic conditions, such as the composition of mobile phase, flow rate and column temperature, on the enantioseparation were systematically investigated. It was experimentally shown that the MIP had specific interactions and high affinity with the template molecule. The MIP could effectively resolve the rac-1, 1'-bi-2 naphthol, and the separation factor was found to be 12.25 under the following conditions: mobile phase, acetonitrile-acetic acid (99: 1, v/v); flow rate, 1.2 mL/min; column temperature, 30 degrees C. The addition of acetic acid to the mobile phase can improve the peak shape, and the lower flow rate and lower column temperature is better for the separation. Further, other substrates which have the similar structure with 1, 1'-bi-2-naphthol, i. e, 5, 6, 7, 8, 5', 6', 7', 8' octahydro-1, 1'-bi-2-naphthol and 1, 1'-binaphthalenyl-2-amino-2'-ol were also resolved partly by optimizing the HPLC conditions, with separation factors of 1.51 and 2.40, respectively. PMID- 17288137 TI - [Separation and purification of 2-chloro-5-trichloromethylpyridine from products of photochemical chlorination of 3-methylpyridine using preparative liquid chromatography]. AB - A preparative high performance liquid chromatographic technique was used to separate and purify 2-chloro-5-trichloromethylpyridine from the products of photochemical chlorination with 3-methylpyridine as raw material. The elution mode, the flow rate of the mobile phase and injection volume were optimized. The optimum operation parameters were selected as follows: Zorbox-C,18 reversed-phase column with the flow rate gradient elution of 30% acetonitrile in water as the mobile phase (gradient elution program: 0 - 8 min at 4 mL/min, 8 - 14 min at 10 mL/min), and a diode array detector with wavelength set at 240 nm, injecting volume of 100 microL. The average recovery rate was 82.7% and relative standard deviation (RSD) was 4.0% (n = 5). High purity (99.01%) product was obtained. The effective and accurate method has been successfully applied to the preparation of pure 2-chloro-5-trichloromethylpyridine. PMID- 17288138 TI - [Simultaneous determination of aflatoxins, zearalenone and ochratoxin A in cereal grains by immunoaffinity column and high performance liquid chromatography coupled with post-column photochemical derivatization]. AB - A method was developed for the simultaneous determination of aflatoxins (AFs) (B1, B2, G1 and G2), zearalenone (ZEA) and ochratoxin A (OTA) in cereal grains by high performance liquid chromatography (HPLC) with fluorescence detection after immunoaffinity column clean-up and post-column derivatization. Cereal grain sample was extracted with methanol-water (80: 20, v/v). The extract was purified by immunoaffinity column and the toxins were separated by reversed-phase HPLC, and quantified with fluorescence detection after photochemical derivatization. The separation was performed on a Nova-Pak column (3.9 mm i. d. x 150 mm, 4 microm, Waters) with a linear gradient of methanol-acetonitrile-1% phosphoric acid mixture. The calibration curves for mycotoxins were made in the concentration range of 0.24 - 6.0 for AFs ( B1, B2, G1 and G2), 4.0 - 100.0 for ZEA and 0.5 - 40.0 microg/L for OTA. Recoveries of the different cereal grains (wheat, rice, rye) spiked with mycotoxins at levels ranged from 0.24 -1.0 microg/kg for AFs (B1, B2, G1 and G2), 4.0 -16.0 microg/kg for ZEA and 0.5 - 3.0 microg/kg for OTA were from 70.8% to 94.0% and relative standard deviations were between 2.79% and 9.38%. The limits of detection were 0.24 Rg/kg for AFs (B1, B2, G1 and G2), 0.5 microg/kg for OTA and 4.0 microg/kg for ZEA. PMID- 17288139 TI - [Simultaneous determination of residues of 12 amide herbicides in soybeans by high performance liquid chromatography]. AB - An analytical method was developed for the simultaneous determination of 12 amide herbicide residues in soybeans. The 12 amide herbicides were extracted with acetone from soybean samples. The extract was cleaned up using a Florisil cartridge, and then determined by high performance liquid chromatography. Kromasil 100-5 C18 column (4.6 mm i. d. x 250 mm, 5 microm) as analytical column, pure water-acetonitrile as mobile phase with a flow rate of 1.0 mL/min and gradient elution, and a diode array detector set at 210 nm were used. The recoveries of amide herbicides from soybeans spiked at levels of 0.05, 0.1 and 1.0 mg/kg were in the range of 75% - 102% with relative standard deviations of 1.9% - 16.1%. The method has good linear in the range of 0.05 - 1.0 mg/L for each analyte (nu > 0.999). The detection limit for each amide herbicide was less than 0.05 mg/kg. The method is simple, rapid and accurate. It can be used for the inspection of amide herbicide residues in soybeans. PMID- 17288140 TI - [Simultaneous determination of inhibitive components in anti-acne cosmetics by reversed-phase high performance liquid chromatography]. AB - The inhibitive components in anti-acne cosmetics including spironolactone, benzoyl peroxide, and tretinoin were simultaneously determined by reversed-phase high performance liquid chromatography (RP-HPLC). The cosmetics were extracted with methanol by microwave and analyzed by high performance liquid chromatography. The HPLC conditions were as follows: Kromasil C18 column (4.6 mm i. d. x 250 mm, 5 microm), methanol and phosphate buffer as mobile phase with gradient elution at a flow rate of 1.0 mL/min, UV detection at 265 nm. Three components were separated completely within 11 min. The calibration curves of the three compounds were linear (nu > 0.999 9) between 1 and 200 mg/L. The average recoveries were from 88.2% to 106.7% with relative standard deviations lower than 3. 1%. The detection limits (S/N = 3) were 0.101 mmicrog for spironolactone, 0.100 microg for benzoyl peroxide, and 0. 107 microg for tretinoin. The method is simple and rapid with high accuracy, and suitable for the determination of the 3 inhibitive components in anti-acne cosmetics. PMID- 17288141 TI - [Simultaneous analysis of theaflavins and catechins by capillary electrophoresis]. AB - In order to monitor the changes of theaflavins and catechins during the process of tea polyphenol oxidation, a rapid, accurate, sensitive and convenient analytical method was established. The optimum analytical conditions for simultaneous analysis of four theaflavins (TFs) and six catechins by capillary electrophoresis were investigated. The electrolyte solution consisted of 200 mmol/L boric acid (pH 7.7), 10 mmol/L potassium dihydrogenphosphate, 9 mmol/L beta-cyclodextrin and 27.5% acetonitrile. The experimental conditions of the instrument were selected as follows: voltage 25 kV, column temperature 30 degrees C, and detection wavelength 200 nm. Ten constituents could be separated from each other completely within 8 min and each one had a good linear relationship between its peak area and corresponding concentration (nu = 0.990 7 - 0.999 8). Furthermore, their detection limits were from 0.39 to 0.88 microg/mL, the mean recoveries varied from 91.5% to 113.5%. The relative standard deviations were less than 5%. All the above results showed that the developed method is especially suitable for the analysis of theaflavins and catechins. PMID- 17288142 TI - [Separation of phthalates in non-aqueous micelle using capillary electrokinetic chromatography]. AB - On the basis of non-aqueous capillary electrophoresis (NACE) and micellar electrokinetic chromatography (MEKC), a novel technique, non-aqueous micellar electrokinetic chromatography (NAMEKC), has been established. NAMEKC has the advantages of NACE and uses the separation mechanism of MEKC, showing special advantages for separation of hydrophobic compounds. Separation of three of the priority pollutants by U. S. Environmental Protection Agency (EPA), i. e. dimethyl phthalate (DMP), diethyl phthalate (DEP), and dibutyl phthalate (DBP), were realized in 15 min. Important factors on separation, such as the amount of water added in the electrophoretic running buffer, the acidity of water phase, the organic additive, and the concentration of sodium dodecyl sulfate (SDS), were investigated. The proportion of water in the electrophoretic running buffer could affect the current and the stability of SDS micelle. Organic additives and the acidity of water phase showed no effect on increasing resolution. The concentration of SDS was a dominant factor, affecting the partition of analytes in micelle. DMP, DEP, and DBP were separated in a short time under the optimized operation conditions using 20 mmol/L NaH2PO4 and 120 mmol/L SDS in formamide/water (9/1, v/v). The application of NAMEKC leads to successful separation of the three typical hydrophobic compounds, which provides a novel means to separate and analyze hydrophobic compounds. PMID- 17288143 TI - [Analysis of chemical components in tobacco flavors using stir bar sorptive extraction and thermal desorption coupled with gas chromatography-mass spectrometry]. AB - A novel method for the analysis of chemical components in tobacco flavors was established using stir bar sorptive extraction (SBSE) and thermal desorption coupled with gas chromatography-mass spectrometry (GC-MS). The different parameters affecting the extraction of the analytes from the samples to the poly (dimethylsiloxane) (PDMS) coated stir bars and the conditions affected thermal desorption were investigated. The optimized extraction conditions were that the sample was extracted with a stir bar (10 mm length and 0.5 mm thickness) at 1 100 r/min for 1 h at ambient temperature. Desorption was carried out from 20 degrees C ramped to 250 degrees C at 60 degrees C/min and hold for 2 min under a helium flow of 50 mL/min in the splitless mode while maintained the cryofocusing temperature of - 100 degrees C in a CIS-4 injector of the GC-MS system. Finally, the CIS-4 injector was raised to a temperature of 280 degrees C and the analytes were separated by GC and detected by MS using full scan mode (m/z 35 - 400). Under the described conditions, about 30 components were identified from the tobacco flavors, and the major components included esters, ketones, aldehydes, etc. The average relative standard deviation (RSD) of peak areas of 30 components for 6 determinations was less than 10%. The good repeatability made SBSE a powerful tool for the routine quality control analysis of chemical components in tobacco flavors. PMID- 17288144 TI - [Study of pyrolysates of flue-cured tobacco leaves and stems]. AB - To further understand the effect of tobacco stems in tobacco blend, a detailed comparative study of chemical components of tobacco leaves and stems before and after combustion was carried out. Pyrolysis of tobacco leaves and stems was carried out by a CDS Pyrolyser 2000 coupled to a Finnigan 8000(TOP) Gas Chromatograph and a Voyager Mass Spectrometer (GC-MS). A modified apparatus of pyrolysis was used to emulate the behavior of combustion of cigarette. A set of pyrolysis conditions was also developed that approximated those occurring in the pyrolysis region of the burning cigarette. The conditions included heating the sample at 20 degrees C/ms from 30 degrees C to 300 degrees C, 600 degrees C and 900 degrees C in air, and their pyrolysates were analyzed by GC-MS. The results indicated that the values of routine chemical constituents in tobacco leaves and stems were obviously different. The pyrolysates belonged to numerous classes of compounds such as hydrocarbons, alcohols, phenols, aldehydes, ketones, nitriles, alkaloids etc. The kinds of pyrolysates of tobacco leaves and stems were positively related to the pyrolysis temperature levels. On the other hand, at the same temperature level, the types of the pyrolysates from the tobacco leaves were much more than those from the tobacco stems. PMID- 17288145 TI - [Study of pyrolysates of beta-carotene in tobacco]. AB - Relationships between tobacco compounds and smoke products are complex and often difficult to unravel. Pyrolysis experiments have frequently been used to establish such relationships. The relevance of pyrolysis experiments to the behavior of tobacco constituent in a burning cigarette was studied. A set of pyrolysis conditions has been developed to study the effect of thermal degradation of beta-carotene to the cigarette smoke quality, and the conditions was approximated to those occurring in the pyrolysis region of the burning cigarette. The pyrolysates of beta-carotene were investigated in air, 10% O2 (in N2) and N2 at three temperature levels of 300 degrees C, 600 degrees C and 900 degrees C, respectively. The pyrolysates were adsorbed by solid-phase microextraction (SPME) and then analyzed by gas chromatography/mass spectrometry (GC/ MS). Under the different conditions, the major pyrolysates from beta carotene are hydrocarbon compounds such as toluene, p-xylene, 1, 2, 3, 4 tetrahydro-1, 1, 6-trimethyl-naphthalene and 2, 7-dimethyl-naphthalene, and some important flavors existing in cigarette smoke such as isophorone, 2, 6, 6 trimethyl-1-cyclohexene-1-carboxaldehyde, beta-ionone and 5, 6, 7, 7a-tetrahydro 4, 4, 7 a-trimethyl-2 (4H)-benzofuranone. The amount of these pyrolysates alters with the change of pyrolysis temperature levels and the concentration of oxygen. PMID- 17288146 TI - [Analysis of C9 fraction of pyrolysis gasoline by gas chromatography and gas chromatography/mass spectrometry]. AB - The constituents of C9 fraction of pyrolysis gasoline were analyzed by gas chromatography (GC) with flame ionization detector (FID) and gas chromatography/mass spectrometry (GC/MS). A 100 m x 0.25 mm i. d. x 0.5 microm PONA column was used to improve the separation efficiency and sample load compared with the standard PONA column of 50 m x 0.20 mm i. d. Identifications of compounds were based on the standards of n-alkanes and a few aromatics, high accuracy retention time simulation and live retention time database, and cross references with MS data. The search in live retention time database gives a few possible compounds that were co-eluting or adjacent from each other. While the MS search results for each peak always report 10 or even more compounds who has similar fragments. The cross-reference of the above method yields much more reliable identification results than normal GC/MS search. Quantitative analysis of each compound and the carbon number distribution were performed by GC with FID. Thirty-nine compounds with contents more than 0.2% in the C9 fraction were identified. The relative standard deviation of quantitative analysis was below 5%. It provides a reliable method for detailed analysis of C9 fraction. PMID- 17288147 TI - [Comparison of chemical components of essential oils in needles of Pinus massoniana Lamb and Pinus elliottottii Engelm from Guangxi]. AB - Essential oils were extracted by steam distillation from the needles of Pinus massoniana Lamb and Pinus elliottottii Engelm grown in Guangxi. Various factors such as pine needle dosage and extraction time which may influence the oil yield were investigated. The optimum conditions were found to be as follows: pine needle dosage 700 g, extraction time 5 h. The essential oil yields from the needles of Pinus massoniana Lamb and Pinus elliottottii Engelm were 0.45% and 0.19%, respectively. Moreover, the chemical compositions of the essential oils were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Sixty four components in the essential oil from needle of Pinus massoniana Lamb were separated and twenty of them (98.59%) were identified while seventy three components in the essential oil from needle of Pinus elliottottii Engelm were separated and twenty nine of them (94.23%) were identified. Generally, the compositions of the essential oils from needles of the two varieties were similar but the contents of some compounds differed greatly. Especially, the content of alpha-pinene in the essential oils from Pinus massoniana Lamb needles was 2.6 times as that from Pinus elliottottii Engelm needles, but the content of beta-pinene was less than the latter. Mono- and sesquiterpenes were the main composition of the essential oils from Pinus massoniana Lamb and Pinus elliottottii Engelm needles. PMID- 17288148 TI - [Determination of acrylamide in foods by gas chromatography-mass spectrometry]. AB - A confirmatory method is presented for the determination of acrylamide in different food products by gas chromatography-mass spectrometry (GC-MS). The method is based on the extraction of acrylamide with and methanol, and purification with Carrez I zinc sulfate) and Carrez II (potassium hexacyanoferrate) solution, followed by bromination onto the acrylamide double bond. The derivative was extracted with ethyl acetate/hexane (4: 1, v/v), and converted to the stable 2-bromopropenamide by dehydrobromination using 10% triethylamine, then analyzed by GC-MS, employing 13C3-acrylamide as internal standard. In-house validation data for flour and bread showed good accuracy and precision of the method. The recoveries of acrylamide in the French fries and bread were all in the range from 80% to 110% after correction of analyte loss by the internal standard at three spike levels of 0.02, 0.05 and 0.2 mg/kg, and relative standard deviations (RSDs) no more than 12.7%. The limits of detection for flour and bread were estimated at 5 microg/kg. PMID- 17288149 TI - [Determination of 25 organochlorine pesticides in tea by gas chromatography-mass spectrometry]. AB - A high performance gas chromatography-mass spectrometry (GC-MS) method for the determination of 25 organochlorine pesticides in tea has been developed. The samples of tea were extracted with n-hexane-acetone (2: 1, v/v). The extract was purified by using a Florisil column with n-hexane-ethyl acetate (9: 1, v/v) as elution solvent. Chromatographic analysis was performed on a DB-35MS capillary column. Satisfactory separation and sensitivity of 25 organochlorine pesticides were obtained with the proposed method. The analytical results show the working curves for 25 organochlorine pesticides were linear in the range of 0.010 - 0.500 mg/L by GC-MS on selective ion monitoring mode. The recoveries of 25 organochlorine pesticides at spiked levels of 0.01 -0.20 mg/kg were 70.8% - 105.5%, and relative standard deviations (RSDs) were 1.6% - 12.7%. The limits of quantitation were 0.01 mg/kg except that for endosulfan I and endosulfan II that were 0.02 mg/kg. PMID- 17288150 TI - [Determination of imidacloprid residues in vegetable and tea samples using liquid chromatography-mass spectrometry/mass spectrometry]. AB - A liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method was developed for the determination of imidacloprid in vegetable and tea samples. The sample was first extracted with acetonitrile and then cleaned up with Florisil and active charcoal column. The precursor ion/product ion transitions m/z 256.0/209.3 and m/z 256.0/175.2 were monitored, and m/z 209.3 was used for quantification. The good linearity was obtained in the range of 0.01 - 0.5 mg/L with the correlation coefficients (nu2) more than 0.997. The limit of quantification was 0.01 mg/kg. The recoveries were 76% - 90% at the spiked levels of 0.01, 0.05 and 0.2 mg/kg with the relative standard deviations of 7.4% - 11.0%. The method is rapid, sensitive and specific for imidacloprid analysis. PMID- 17288151 TI - [Simultaneous determination of residues of organochlorine and pyrethroid pesticides in tea by microwave assisted extraction solid phase microextraction gas chromatography]. AB - The issue of residues including organochlorine and pyrethroid pesticides in tea has made a great attention of researchers and customers in the world. Although some analytical methods have well been established to detect these pesticides, the sample preparations are generally laborious, time-consuming, and some of the procedures caused environmental pollution. Solid phase microextraction (SPME) is a novel sample preparation technique since it is of simplicity, high efficiency and solvent free. SPME was firstly developed to address the need to facilitate environment monitoring. In recent years, great efforts have been made in the analysis of pesticide residues in agricultural products by SPME. In this research, a microwave assisted extraction solid phase microextraction-gas chromatography (MAE-SPME-GC) was applied for the simultaneous determination of organochlorine and pyrethroid pesticides, such as benzene hexa chlorides (alpha BHC, beta-BHC, gamma-BHC and delta-BHC), 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2, 2, 2-trichloroethane (o, p'-DDT), 2, 2-bis (4-chlorophenyl)-1, 1-dichloroethylene (DDE), 2, 2-bis (4-chlorophenyl)-1, 1-dichloroethane (DDD), 2-(2-chlorophenyl)-2 (4-chlorophenyl)-1, 1, 1-trichloroethane (p, p'-DDT), cypermethrin and fenvalerate. All the tested pesticides were baseline separated under the experimental conditions, except for DDD and o, p'-DDT. The concentration of each pesticide was calibrated by external standard method. The linearities were found to be in the correlation coefficient range of 0.970 5 to 0.998 4 for the tested pesticides between the mass concentrations and peak areas, except for fenvalerate. The recoveries, relative standard deviations and detection limits for the 10 pesticides were 64% - 121%, 10.4% -22.9%, and 1 - 50 ng/L, respectively. The proposed method was successfully applied to the determination of organochlorine pesticide residues in three kinds of teas from the local market. The experimental results demonstrated that MAE-SPME-GC was a fast, sensitive and green technique for the analysis of trace quantity of pesticides in solid substrate foods. PMID- 17288152 TI - [Hollow fiber liquid phase microextraction of tramadol from water and biological samples]. AB - A novel technique of liquid phase microextraction supported by hollow fiber membrane (LPME-HFM) was applied to extract tramadol in tap water, urine and human plasma. At room temperature (20 degrees C), polyvinylidene fluoride hollow fiber membrane (PVDF-HFM) was employed. In the procedure of extraction, 4 microL of organic solvent (toluene) was used in individual extraction. Pethidine was used as the internal standard (IS) in the sample analysis by gas chromatography with flame ionization detector (GC-FID). The optimized conditions for tramadol extraction was as follows: toluene as organic solvent, 4 mL sample solution added with 0.1 mL of 1 mol/L NaOH solution, extraction time of 15 mm, and stirring speed of 300 r/min. The sample solutions, containing a series of concentrations of tramadol, 0.05, 0.10, 0.50, 1.0, 5.0, 10.0 mg/L, were analyzed. The good linearities were obtained for water, human urine and human plasma samples with the correlation coefficients of 0.999 7, 0.994 8 and 0.998 5, respectively. The detection limits can reach 0.01 mg/L for water and human urine and 0.05 mg/L for human plasma. The relative standard deviations (RSDs) were 10.6% and 5.15% for water, 18. 1% and 4. 03% for urine solution at the spiked levels of 0.1 and 1.0 mg/L. The RSDs were 16.6% and 4.15% for plasma solution at the spiked levels of 0.5 and 1.0 mg/L. In comparison with conventional method, this method is simple, sensitive, fast, inexpensive, and environmentally friendly. It can be applied to pharmaceutical and forensic analysis. PMID- 17288153 TI - [Analysis of cis-9, trans-11-conjugated linoleic acid in milk fat by capillary gas chromatography]. AB - Conjugated linoleic acid (CLA) is a term representing a mixture of positional and geometric isomers of octadecadienoic acid with a conjugated double bond system. Conjugated linoleic acid has attracted a great deal of interest among nutritionists because it is a natural fat component that appears to have a number of health improvement properties. The cis-9, trans-11-CLA is the major CLA isomer found in dairy products accounting for 75% to 90% of the total CLA in milk fat. A capillary gas chromatographic method equipped with a flame ionization detector for the analysis of the cis-9, trans-11-CLA in milk fat was developed. The cis-9, trans-11-CLA was extracted with hexane-isopropanol, methylated with methanol sodium methylate and cis-9, trans-11-CLA was separated and quantified using gas chromatography. Retention time of the peaks was used for qualitative analysis, while external standard method was used for quantitative analysis. The recovery of the cis-9, trans-11-CLA was 100.26%. The relative standard deviation was 1.9% (n = 6). This method presented is advantageous for high precision, high sensitivity analysis with smaller sample size and simpler pretreatment. It would be of significance for analyzing the contents of other fatty acids in the milk and milk products. PMID- 17288154 TI - [Simultaneous determination of triazine herbicide residues in maize by gas chromatography]. AB - A gas chromatographic method was developed for the determination of simeton, simazine, atrazine, propazine, terbumeton, terbuthylazine, cyprazine, simetryn, prometryn, terbutryn, methoprotryne, hexazinone residues in maize. The triazine herbicide residues were extracted with acetonitrile by blender and then cleaned up on a strong cation-exchange (SCX) solid-phase extraction cartridge. The SCX cartridge was conditioned with acetone, methylene chloride, washed with methylene chloride, acetone and eluted with methanol-water (9: 1, v/v) solution saturated potassium chloride. As a result, most interfering impurities were removed in the SPE cleanup procedure. The gas chromatographic analysis was performed on a capillary column (DB-5, 30 m x 0.25 mm i. d. x 0.25 microm) and determined by nitrogen phosphorus detector (NPD). Twelve triazine herbicides were effectively separated on this column. Diazinon was used as the internal standard for the determination. Linear correlation coefficients of the 12 herbicides were higher than 0.998 in the range of 0.01 to 2.0 mg/L. The limits of quantitation of the method were 0.01 mg/kg for these compounds. Average recoveries of these herbicides from spiked samples ranged from 84.0% to 106.8% at fortification levels of 0.01 - 0.5 mg/kg and the relative standard deviations (RSDs) were between 0.9% and 4.7%. The method is suitable for the simultaneous determination of a wide range of triazine herbicides in maize in commodities inspection. PMID- 17288155 TI - [Simultaneous determination of gallic acid and protocatechuic acid in Choerospondias axillaries by RP-HPLC]. PMID- 17288156 TI - [Simultaneous determination of sixteen hormones in cosmetics by RP-HPLC]. PMID- 17288157 TI - [Determination of swainsonine by ISC]. PMID- 17288158 TI - [Chiral separation of citalopram intermediate compounds by CE]. PMID- 17288159 TI - [Improved enantioseparation of basic drugs by CE using chemically bonded polyethyleneimine coated capillary]. PMID- 17288161 TI - [Study on the carrier gas used in GC-MS analysis]. PMID- 17288160 TI - [Determination of chloramphenicol in cosmetics by GC-MS]. PMID- 17288162 TI - [Rapid determination of bicarbonate in mineral waters by IEC]. PMID- 17288163 TI - [Tobacco in statistics at the turn of the new century]. AB - The paper presents the information about the tobacco products (cigarettes, rolled tobacco, pouch, cigars and non-commercial products) available in different countries of the world and the methods of their application. The popularity of smoking among the youth and adults as well as the differences resulting from tobacco smoking depending on the sex has been discussed. A particular attention was paid to the fact that the age of tobacco initiation is earlier and earlier, and also, that the number of smoking women, especially in the developing countries is growing. The growing significance of China, the main tobacco manufacturer, and China National Tobacco Corporation as the largest tobacco concern in the world, were indicated. The costs related to tobacco smoking, which are borne by the smoking person and the whole society was presented. PMID- 17288165 TI - [Passive smoking and frequency of occurrence of disease symptoms in the respiratory system in children aged 0-7]. AB - Passive smoking is the problem all of us but the most harmful is for health of the children. The work aims was the assessment of frequency of occurrence of disease symptoms in the respiratory system in children up to 7 years of age depending on exposure to passive smoking. 100 children admitted to the Regional Children's Hospital in Bydgoszcz were subject to research; all of them living in the Kujawsko-Pomorskie Voivodeship. Research was conducted from May until December 2003. Information concerning family and social situation of the group examined was gathered; also data on disease history and environment was taken. The most frequently occurring respiratory system diseases were: rhinitis--in 69 (69%) children, pharyngitis--in 59 (59%) patients, bronchitis--58 (58%) children, laryngitis--30 % cases, and pneumonia was observed in 23 (23%) children examined. The lowest number--only 3 (3%) persons had sinusitis. The effort was also taken to determine the relation between the frequency of occurrence of symptoms and chronic diseases in the respiratory system and exposure to passive smoking. Research showed that the frequency of occurrence of bronchitis and hoarseness remains in significant statistical relation with passive smoking. PMID- 17288164 TI - [Evaluation of infants and younger children passive smoking at home and prevalence of their lower respiratory tract infectious]. AB - The nicotine's metabolites were determined in urine of 92 children--59 children of smoking parents (SP) and 33 of non-smoking parents (NSP). The level of metabolites of nicotine and the ratio of the nicotine's metabolites to creatinine concentration were analyzed in infants (older than 5 months) and children 2-4 years old. Moreover the frequency of bronchitis and pneumonia in children was estimated on the basis of the interview with their parents. The nicotine's metabolites concentration was significantly higher in urine of children of SP than in urine of NSP children, as well in the group of infants as in children aged 2 to 4 years. Respiratory tract infections were frequent in 69.4% of SP children and in 21.1% of NSP children. In addition, the mean and the highest level of metabolites of nicotine in urine of SP children were multiple higher in comparison to the levels found in the group of NSP children suffering from the respiratory tract infections with equal frequency. PMID- 17288166 TI - [The expression of gene encoding folitropin receptor in granulosa cells in women smoking cigarettes and nonsmokers participating in vitro fertilization programme]. AB - This research was stated on the group of infertile patient taking part in in vitro fertilization. The whole group of 60 random patients was divided into two subgroups: 10 persons smoking cigarettes and 50 nonsmokers. The number of follicles obtained after controlled ovarian hiperstimulation, the number of mature and immature oocytes and concentration of 17beta-estradiol in serum at the hCG day were measured for all women. There was also calculated the number of granulosa cells and the relative expression of the gene encoding FSHR. Comparing all testing groups, in smokers the worse ovarian answer for hiper-stimulation was observed. It was characterized by both the lower number of follicles and oocytes and also the lower concentration of estradiol in serum at hCG day. There was also observed lower number of granulosa cells in fluid from all folicles at diameter > 12 mm in smoking patients compared with nonsmokers. Analizing the relative expression of gene coding FSHR in granulosa cells significant differences between these two groups were demonstrated. The evaluation of the expression level showed its reduction in smokers (2). To compare it the average level of expression in nonsmokers was 24. Smoking cigarettes is correlated with the lower number of granulosa cells and the lower expression level of the gene coding for folitropin receptor. PMID- 17288167 TI - [The impact of cigarette smoking on oocytes and embryos quality during in vitro fertilization program]. AB - The aim of the study was to investigate the influence of smoking on different parameters in woman treated by in vitro fertilization. Twenty-seven patients undergoing IVF were classified as smokers and 32 as non-smokers on the basis of medical history. Smokers had decreased number of retrieved oocytes compared with non-smokers (p < 0.05). Our study demonstrates that active cigarette smoking increases the zona pellucida thickness of oocytes and decreases a quality of oocytes. Cigarette smoking is associated with reduced number of embryo obtaining after classical in vitro fertilization in smokers compared to non-smokers, There was no significant difference in number embryos obtained after ICSI treatment in both groups. Women who smoked had also statistically significantly lower quality of embryos versus non-smokers patients. The clinical pregnancy rate per cycle in smokers was significantly lower. PMID- 17288168 TI - [Apoptosis of alveolar lymphocytes in sarcoidosis and in control group is more frequent in smokers than in nonsmoking persons]. AB - Cigarette smoking enhances apoptosis rate of alveolar macrophages. However, little is known about the appearance and extension of apoptosis in bronchoalveolar lavage (BAL) lymphocytes originating from smoker individuals, both in pulmonary sarcoidosis (the disease characterized by lymphocytic alveolitis) and in controls. BAL was carried out in 60 nontreated patients with pulmonary sarcoidosis, subdivided acc. smoking status and in 22 control persons, free of any lung pathology. BAL (alveolar) lymphocytes were a) stained for TUNEL; b) permeabilized and stained with PI for late apoptosis/cell cycle analyses; c) immunophenotyped, including CD95, CD95 Ligand, Bcl-2, Bcl-XL, Bak and insulin like growth factor-I (IGF-I) expression. BD FACSCalibure flow cytometer, PC Lysys and ModFit software were applied. The low number of AL entered apoptosis, which was confirmed by both techniques. Cigarette smokers were characterized by higher AL apoptosis percentage in respective subgroups (sarcoidosis: 0.6 +/- 0.13 in nonsmokers vs 0.9 +/- 0.23 in smokers; controls: 0.85 +/- 0.23 in nonsmokers vs 1.5 +/- 0.35 smokers, median +/- SEM, p < 0.05); the proliferation rate was lower. Decreased IGF-I expression in AL of sarcoidosis smokers was observed (13.5 +/- 9.2 vs 46.0 +/- 6.0 in nonsmokers, p < 0.05). No differences were found between studied groups in expression of Bcl-2, Fas and FasL molecules (except significantly declined ratio of CD8+FasL+ cells in sarcoidosis nonsmokers). AL apoptosis rate was positively correlated with respective alveolar macrophage results (Rs = +0.59, p < 0.00001) and negatively with CD4/CD8 ratio (Rs = -0.32, p < 0.001); no correlation was found with lung function test results and with Bcl 2, Fas and FasL expression in BAL cells. Apoptosis of alveolar lymphocytes was more frequent in nonsmokers both in pulmonary sarcoidosis and in controls; lower AL percentage proliferates. These phenomena seem to participate in lower AL percentage, observed in smoker subgroup of sarcoidosis. Some mechanisms of local apoptosis alterations in smokers may be common for alveolar lymphocytes and macrophages. PMID- 17288170 TI - The occurrence of chronic obstructive pulmonary disease (COPD) in cigarette smoking families. AB - Chronic Obstructive Pulmonary Disease (COPD), one of the most common respiratory problems of adults, is caused in 90% by cigarette smoking. The aim of this study was to evaluate the frequency of occurrence of COPD among cigarette smokers and among the passive smokers living with them. The research group consisted of 190 families in which at least one person was a smoker. A total of 500 adults were included, among them 290 were active smokers and 210 were passive smokers. The questionnaire including demographic and smoking habit data was used in the research. Additional tests, like spirometry, allowed diagnosing COPD and chest X ray allowed diagnosing emphysema. Chronic obstructive pulmonary disease (COPD) was diagnosed in case of 46.4% of active smokers and 28.0% of passive smokers. Respiratory symptoms, such as cough, expectoration and dyspnoea, occurred more frequently among active than passive smokers (p < 0.001). Changes in respiratory system in chest X-ray and obturation in spirometry were noticed at 114 of passive smokers as a result of long lasting smoke inhaling. Members of the families in which there is more than one active smoker more often suffer from COPD, smoke ten cigarettes per 24 hours more and smoke ten years longer than members of the families in which there is only one active smoker. Active smokers are more frequently affected by COPD than ex-smokers and passive smokers. Members of families in which there are two active smokers more often suffer from COPD than those who have only one active smoker in the family. Spirometry should be a stable element of early COPD diagnosis at the family members of an active smoker. PMID- 17288171 TI - [The comparative analysis: the occurrence of acute respiratory system infections and chronic diseases among active smokers and non-smokers]. AB - Cigarette smoking is one of the factors causing a lot of health problems. Breathing the smoke makes the development of arteriosclerosis and ischemic heart disease faster and the risk of myocardial infarction much higher. Toxic substances contained in the smoke induce inflammatory processes in bronchial tree, which finally leads to the destruction of lungs. One of the way of preventing complications in the circulatory system and stopping the inflammatory process in lungs is to give up the habit of smoking. Within the period of three years the group of more than 1000 people (smokers and non-smokers) was examined and the analysis of occurrence of acute respiratory system infections and chronic diseases was conducted. In the studies the questionnaire prepared by the author of the paper, some specialistic studies and medical reports were used. The achieved results show that more and more women smoke as many cigarettes as men and for as many years as they do. Both men and women who graduated either a grammar school or a university smoke more often than with elementary level of education. People who smoke suffer more often from numerous acute respiratory tract infections and must more often pay a visit to general practitioner. Considering the sex there are no statistically significant differences in the occurrence of chronic pulmonary diseases and the cardiovascular system. The achieved results show the changes of the attitude to smoking in Polish society. The increase of the consumption of cigarettes among women with high education is very worrying. It is a serious challenge for the whole medical staff. PMID- 17288172 TI - [Tobacco smoking and the frequency of arterial hypertension in adults]. AB - This study aimed to evaluate the influence of the tobacco smoking on the frequency of arterial hypertension in adults. This study involved 160 sub. jects, aged 30 to 60 years. Study group included hypertensive subjects and control group healthy adults. The arterial blood pressure was measured and tobacco smoking was evaluated based on the questionnaire. The obtained results were found the same percent of smokers in both groups. In study and control group, it was shown comparable values of blood pressure in smokers and nonsmokers. A farther study including more number of subjects and influence nutrition and nonnutrition factors on blood pressure in adults are necessary. PMID- 17288173 TI - [Tobacco smoking, physical inactivity and stress in 40-year-old patients with cardiovascular diseases]. AB - In the randomised study of 1037 40-year-old inhabitants of the City and the (former) Province of Poznan, born 1959, the occurrence of such cardiovascular diseases as arterial hypertension and ischemic heart disease was established in this subpopulation. Their association with the life-style of the subjects was also assessed. A structured questionnaire was developed for this study, comprising the basic socio-demographical data, the elements of life-style, a self assessment of one's health as well as subjective and objective medical examination, and the results of selected laboratory tests. The prevalence of arterial hypertension was established at 22.47%, while that of ischemic heart disease at 3.96%. Such negative to health behavioural patterns as tobacco smoking (36% of smokers were hypertensive, obesity--29% had BMI in excess of 30, physical inactivity in 52% of the hypertensive subgroup)--were revealed among those with cardiovascular diseases. Poor coping with emotional stress was also found among the latter group. The results indicate the necessity of more intensive health education, directed at both the healthy population and at those with cardiovascular diseases. PMID- 17288174 TI - [Significance of smoking and cigarette abstinence regarding anxiety in gynecologic patients in a perioperative period]. AB - Smoking cigarettes adds to risk of anesthesia and surgery, and also may influence anxiety. However, cigarette abstinence may increase preoperative stress. The study aimed at exploring the relationship between smoking and anxiety in gynaecologic patients in the perioperative period, and also finding out whether the abstinence and history of unsuccessful cessation attempts are connected with an anxiety pattern at that time. A relationship between anxiety and postoperative pain should be also examined. In 24 smokers and 24 non-smokers subjected to hysterectomy the anxiety level was examined by means of both Spielberger's state and trait inventory (STAI) and visual-analog scale (VAS) before and following surgery; maximal pain on the first postoperative day was also assessed by VAS scale. Smokers additionally completed an inventory of smoking behavior. Pre- and postoperatively the anxiety level was comparable in both groups. Before surgery but not after it, state anxiety overtopped the trait in both smokers and non smokers. Postoperatively state anxiety was connected with the trait and morphine consumption. Cigarette abstinence before surgery did not influence anxiety; however, state anxiety correlated with the length of abstinence. In smokers with the history of smoking cessation attempts, preoperative state anxiety was higher. Between smokers and non-smokers no differences in postoperative pain and no significant relationship with the anxiety could be found, Conclusions: 1) Perioperative anxiety is comparable in both smoking and non-smoking gynaecologic patients. 2) Cigarette abstinence before surgery is not connected with any significant anxiety differences. Smokers with the history of unsuccessful cessation attempts preoperatively present with higher state anxiety. PMID- 17288176 TI - [Tooth wear in Hindu betel nut chewers]. AB - Literature data describe the impact of certain factors on oral health. Very well known is habitual chewing of different plant products, including tobacco, which depending on the geographical area and the substances used, have various names. It has been estimated that approximately 200 million residents of the West Pacific Rim and South-East Asia indulge in betel chewing. Betel is composed of a leaf of the betel pepper, lime, tobacco and the nut of the areca palm. This study aimed to assess the degree of abrasive changes in residents of the Korunalaya Leprosy Care Center. The examinations were carried out on 85 patients (45 females and 40 males), aged 35-95 years, at the local dental surgery. Patients had their teeth assessed and they were further interviewed as to the duration of their habit with regard to their sex and age (35-44; 45-64 and > or = 65 years). The abrasive changes were evaluated using Gerasimov's 7-degree scale. Interview data indicate that 71.76% of the patients were habitual betel chewers. Among female patients, third-degree abrasion was the most frequent change while among males- fifth degree (53.3% and 45.0%, respectively). The abrasive changes, increasing with age, can be attributed to the duration of betel chewing. It is worth noticing that a vegetarian diet can be a contributing factor to abrasion as most of the food consumed by Hindus are plants. PMID- 17288175 TI - [An association between tobacco smoking and basic haemodynamic parameters during induction of anaesthesia in gynecologic patients--a pilot study]. AB - Cardiovascular risk is increased in cigarette smokers in the perioperative period and smoking cessation results in its decrease. The pilot study has been designed to assess an association between smoking and arterial blood pressure and heart rate during induction of anaesthesia in gynecologic patients. Significance of smoking cessation before operation in this respect should be also assessed. Systolic, diastolic and mean arterial blood pressures and heart rate were assessed before and after the induction of anaesthesia in gynecologic patients subjected to hysterectomy: 27 smokers and 27 non-smokers. Anxiety level and intraoperative fentanyl use were also analyzed. Examined parameters were compared between smokers who were abstinent for at least one day before operation and those who continued smoking. Arterial blood pressure and heart rate were comparable in both smokers and non-smokers and also in both groups before and after the induction of aneasthesia. Smoking did not result in any modulation of anxiety level and intraoperative fentanyl dosage. Smoking cessation was connected with lower mean arterial pressure before the induction (P = 0,037). Cigarette smoking does not modify values of basic haemodynamic parameters during induction of anaesthesia in gynecologic patients. Smoking abstinence for at least one day before surgery may be connected with a lower mean arterial blood pressure before the induction. PMID- 17288177 TI - [Effect of tobacco smoke on permeability of capillary of pregnant and non pregnant rats]. AB - From among 4200 chemical compounds contained in the tobacco smoke, nicotine and carbon monoxide are responsible for changes in the heart-vessel system to the greatest extent. Additionally, other toxic compounds, including the carcinogenic ones, have a significant impact on the biological activity in the tissues of blood vessels. A particularly complex picture of the detrimental impact of the tobacco smoke is presented in case of pregnant women, fetuses and newborns. The aim of the research was to assess the impact of tobacco smoke on the permeability of capillaries in different tissues of rats (lungs, brain, liver, kidneys) and testing of the potentially protective impact of rutine (3-rutinozide of quercetin). The research on the permeability of capillaries has been carried out applying Evans blue. The animals were divided into 8 research groups: pregnant animals--"control", "rutine", "tobacco smoke", "rutine+tobacco smoke", and non pregnant animals--"control", "rutine", "tobacco smoke", "rutine+tobacco smoke". In the first stage of research (pregnant, non-pregnant-- groups: "rutine" and "rutine+tobacco smoke"), the water rutine solution in a dose of 40 mg/kg of body weight was administered. The non-pregnant and pregnant animals from groups "tobacco smoke" and "rutine+tobacco smoke" were exposed to tobacco smoke via inhalation (1500 mg CO/m3 of air) for 21 days. All the animals were injected with the water Evans blue solution in a dose of 30 mg/kg of body weight. After 30 minutes, the animals were killed by cutting the abdominal aorta, and lungs, brain, liver and kidneys were taken for further testing. The cotinine in the urine was determined by the HPLC method, using norephedrine as the internal standard, after the preceding extraction by means of the liquid-liquid technique. The concentration of cotinine in case of non-pregnant and pregnant females was respectively 11.8 +/- 1.9 pg/ml of urine and 12.0 +/- 2.5 microg/ml of urine. In case of the rats, which received the rutine, the concentration of rutine in the group of non-pregnant females was 9.3 +/- 1.0 microg/ml of urine, and in the group of the pregnant ones 8.5 +/- 1.1 microg/ml of urine. In the lungs of non pregnant animals exposed to tobacco smoke, the decreased permeability of vessels for the albumin-Evans blue complex was proven. The administration of rutine to non-pregnant and pregnant animals did not exert influence on the permeability of vessels in lungs. A similar result was obtained for the lungs of rats receiving the rutine, as well as those exposed to tobacco smoke. In the brain tissue of non pregnant and pregnant animals, a slight decrease in the content of Evans blue was declared as a consequence of tobacco smoke impact. In the groups receiving the rutine, this flavonoid was declared to influence the blood supply of the brain tissue, and the permeability of the vascular walls. In the liver tissue of animals inhaling the tobacco smoke, the permeability of vascular walls for albumin-Evans blue complex was increased. The rutine did not affect significantly the permeability of vessels, whereas the exposure of pregnant females, which received rutine, to smoke decreased the content of Evans blue in the liver tissue. In the tissues of all tested females, no significant differences between the control groups and groups exposed to tobacco smoke as well as rutine+tobacco smoke were detected. The obtained results do not indicate, however, that in case of chronic exposure to tobacco smoke, the rutine has insignificant protective meaning. PMID- 17288179 TI - [Assessment of occurrence frequency of cotinine and trans-3'-hydroxycotinine in chosen body fluid samples]. AB - Kind of the main nicotine metabolites, occurrence frequency of trans-3' hydroxycotinine (HK) and cotinine (K) in mother and foetus serum, amniotic fluid and urine of chosen group of children (10 - 12 years old) determined by planar chromatography with densitometry as well as ratio of (HK)/(K) has been compared. The obtained data allowed to state, that the main nicotine metabolite concentrations (HK and K) were higher in foetus serum in comparison to mother serum. In the case of occurrence both of them ratio of (HK)/(K) was close to 1 in 20% of examined body fluid samples, but it was above this value in significant majority cases. It can be a prove that trans-3'-hydroxycotinine was dominating metabolite of nicotine in these samples and statistically significant more often occur in foetus serum, in the case when cotinine was determined in mother serum. PMID- 17288178 TI - [Determination of nicotine and cotinine in human biological materials and their significance in toxicological studies]. AB - The aim of this study was the preparation of reliable procedure of the determination of nicotine and cotinine both in classic (serum, urine) and alternative biological materials (hair, saliva) and evaluation of their significance for clinical and forensic toxicology. Biological material samples (blood, urine, saliva) were taken from patients after Percutaneous Trans-luminal Coronary Angioplasty (PTCA). The determination of cotinine and nicotine concentration in the biological material should be optimized depending on the aim of analysis. Liquid-liquid extraction procedure and high performance liquid chromatography HPLC/UV-DAD are reliable, specific and relatively cheap. Serum and saliva are valuable biological materials which allow to determine temporary nicotine and cotinine content on the similar level of concentrations. In the near future it will be able to replace blood with saliva sample because of an easy and non-invasive way of sampling. Evaluation of cotinine concentration in urine allows to distinguish the passive from the active tobacco smokers. Hair analysis allows to control a nicotine abstinence as well as a long-term evaluation of the history of smoking. However usage of hair is limited because of difficulty with sampling. Interpretation of results in analysis of alternative materials (hair, saliva) pose a problem because of lack of sampling standardization and lack of standardization of final analysis method. PMID- 17288180 TI - [Cotinine in urine of mother and their newborn and in cord serum and placenta as a biomarker of foetal exposure to tobacco smoke]. AB - In Poland, tobacco smoking by women in a procreational age as well as the pregnant women is a common phenomenon. The aim of the conducted research was to assess the usefulness of cotinine markers in different biological materials- mother and newborn's urine, cord blood se. rum, placenta--as a biomarker of tobacco smoking by delivering women, and dependence between these biomarkers and the newborn's health state. 218 pregnant women (117 smokers and 101 non-smokers), who were checked in at the Perinatology and Gynecology Clinic of the University of Medical Sciences in Poznan, took part in the first stage of the research (period between the twelfth and sixteenth week of pregnancy) carried out between years 2004-2006. In the second stage, 201 pairs of women (89 smokers and 112 non smokers) and their newborns were checked after the women came to hospital to deliver. The research that was conducted showed that both cotinine in the urine of delivering women and in the urine of newborns as well as in the cord blood serum may be used as a biomarker of exposure of a foetus to tobacco smoke. For practical reasons, it must be assumed that the delivering women urine should be the material from choice. The research did not indicate the usefulness of the determination of cotinine in the placenta, in order to assess the exposure of the foetus to the components of tobacco smoke. On the other hand, again it confirmed the influence of tobacco smoking on the newborn's birth parameters, a correlation between the birth weight, body length and cotinine concentration in the urine of a mother makes it possible to predict the lowering of the antropometric parameters of the newborn as a result of tobacco smoking by pregnant women. PMID- 17288181 TI - [Environmental tobacco smoke exposure in pregnancy and postpartum period]. AB - Among available methods to estimate the exposure to tobacco smoke, cotinine, a major metabolite of nicotine is considered the most accurate marker. The aim of this study was to evaluate environmental tobacco smoke exposure in pregnancy and postpartum period. The cohort study was conducted in 2004 and 2006 in public maternity units in Lodz, Poland. The study population consisted of women between 32-36 weeks of pregnancy who have quit smoking within 2 months before pregnancy or no later than three months prior to participation in the study. Women were interviewed twice: during pregnancy and three months after delivery. Self reported non-smoking status was verified using saliva cotinine level. Cotinine level in saliva sample was analyzed using Liquid Chromatography with Tandem Mass Spectrometry. We included into the analysis 62 women who, based on self-reported smoking status and saliva cotinine level were classified as non-smokers. There were no statistically significant differences in mean saliva cotinine level measured in pregnancy and postpartum period. Pregnant women who smoked more cigarettes per day before quitting smoking had significantly higher cotinine level comparing to women who smoked < or = 10 cigarettes per day (p = 0.03). Saliva cotinine level was significantly higher among women exposed to environmental tobacco smoke at home compared to non-exposed (p = 0.02). PMID- 17288182 TI - [The assessment of urinary nicotine metabolites concentration in children and teenagers with oesophagitis]. AB - Tobacco smoke is important pathogenetic agent of stomach digestive and duodenum ulcers, oesophagitis as well as gastro-oesophageal reflux disease. The aim of work was the assessment of urinary nicotine metabolites concentration in children and teenagers diagnosed and treated in Paediatrics Chair of Medical University of Silesia by chronic stomach pains, or oesophagitis and gastrooesophageal reflux disease symptoms. Urine was sampled from 54 persons before gastrofiberoscopy, in which the main nicotine metabolites concentration was determined by ELISA method and given per creatinine concentration. It was shown, that 30% of examined population was intensively exposed to tobacco smoke (actively or passively smoking), but 37% passively exposed to nicotine. Significant higher nicotine metabolites concentration was stated in the currently H. pylori infected sick, however without differences of these biomarkers concentrations between group with oesophagis in endoscopy as well as histopathologic examination and group without these features. PMID- 17288183 TI - [An assessment of active and passive exposure to cigarette smoking among patients after percuteneous transluminal coronary angioplasty (PTCA) with the usage of cotinine level in the serum, urine and saliva. Preliminary study]. AB - The aim of the study was an objective assessment of active and passive exposure to cigarette smoke among patients after percutaneous transluminal coronary angioplasty (PTCA). A questionnaire was answered by 24 patients (18 men and 6 women) aged 48 to 76 (av. 61.2) years. Cotinine (metabolite of nicotine) level was measured in blood, urine and saliva of the patients as objective verification of the questionnaire answers. CONCLUSIONS: 1. Among the PTCA patients 41.6% of them were active smokers. 2. 30% of smokers concealed the fact of active smoking. 3. We assume that smoking habit among the patients should be verified by measurement of cotinine in serum, saliva and urine. 4. The main motivations for smoking cessation were myocardial infarction, PTCA and hospitalizations. 5. All patients were aware of the harmful effects of smoking and were able to identify the main risks. PMID- 17288184 TI - [Tobacco smoking as a source of exposure of pregnant women and newborn on polycyclic aromatic hydrocarbons]. AB - An essential problem related to tobacco smoking is exposure of children in the foetal period and early childhood to toxic compounds. The aim of this paper was to assess the exposure of pregnant women and their newborns to polycyclic aromatic hydrocarbons as a consequence of tobacco smoking. The exposure to tobacco smoke was determined through surveys and cotinine measurement in the urine of pregnant women and newborns, and the exposure to polycyclic aromatic hydrocarbons has been determined by measure of 1-hydroxypyrene in the same biological material. The cotinine concentration in the urine of smoking women and their newborns was respectively 416.0 +/- 319.9 ng/mg of creatinine and 46.5 +/- 37.2 ng/mg of creatinine. In case of non-smoking as well as non-exposed patients and their newborns, the concentration of cotinine was 0. The correlation between the concentration of cotinine in the urine of smoking women and their newborns was shown. The mean concentration of 1-hydroxypyrene in the urine of smoking patients was 0.65 +/- 0.45 ng/mg of creatinine, whereas in the urine of newborns, it was 0.46 +/- 0.41 ng/mg of creatinine. The concentration of 1-hydroxypyrene in the urine of smokers was increased together with the increase of cotinine, and the correlation factor was 0.5128. Such dependence was not indicated for concentrations of these compounds in the urine of newborns of these women. Within the group of non-smoking women, the concentration of 1-hydroxypyene urine of women was 0.25 +/- 0.29 ng/mg of creatinine, whereas among children 0.20 +/- 0.23 ng/mg of creatinine. In both examined group (smoking and non-smoking women) there is a dependence between the concentration of 1-hydroxypyrene in the urine of women and their newborns. The research concerning the assessment of exposure of pregnant women and their newborns to polycyclic aromatic hydrocarbons was conducted, and at the same time it was proven, that the placenta does not constitute a barrier for these compounds, which may freely get into the fetus. Probably for the first time a relatively large group of patients took part in this research. The directly proportional dependence between the concentrations of 1-HP in a mother and a newborn and significantly lower concentrations of this biomarker among the persons who are not exposed to tobacco smoke, indicate that the pro-health behaviours of the future mother (no tobacco smoking) significantly lowers the exposure of foetus to the carcinogenic compounds. PMID- 17288185 TI - [Determination of urinary cotinine and 1-hydroxypyrene and blood carboxyhemoglobine as the biomarkers of tobacco smoke exposure]. AB - The following biomarkers: cotinine, 1-hydroxypyrene (1-OHP) and carboxyhemoglobin (HbCO) were used for the estimation of the tobacco smoke exposure. In our study urine and blood sampled from 98 volunteers were subjected to assessment of the biomarkers concentrations under investigation. According to the self-reports of the volunteers, all of the volunteers were divided into three groups: non smokers, passive and active smokers. The mean values of the biomarker concentrations were calculated for these groups. In order to verify the tobacco smoke exposure specified by volunteers, we tested the real urinary cotinine amount. Based on obtained values of this biomarker, the another volunteer's partition into the groups of nonsmokers, passive and active smokers were done. The new mean values for all of these groups were calculated. The mean values obtained for both group partitions differed. The latter partition gave opportunity to use 1-OHP for the estimation of the tobacco smoke exposure not only for the active smokers but also for the passive smokers. When HbCO was taken into consideration as the biomarker, the estimation of the tobacco smoke exposure of the passive smokers was not significant different, as compared with the group of nonsmokers. The analysis of the correlation between the concentrations of 1 OHP and cotinine gave opportunity for the estimation to tobacco smoke exposure of the passive and active smokers. The estimation of the correlation, between the HbCO and cotinine concentrations was restricted for this purpose. PMID- 17288186 TI - [Determination of 4-(methylnirosamino) -4-(3-pyridyl)-1-butanol (NNA) in urine of pregnant women by means of LC/MS/MS]. AB - An important problem, particularly from the point of view of the medicine, is active tobacco smoking and passive exposure to tobacco smoke of pregnant women and unfavourable health aftermath for the foetus and a newborns resulting from this. The aim of this study was to evaluate the exposure of smoking mothers to tobacco-specific N-nitrosamines, through the measurement of 4-(metylnitrosamino) 1-(3-pyridyl)-1-butanol (NNAL) in urine. The evaluation of tobacco smoking was performed on the basis of questionnaire studies and determination of cotinine in urine. The questionnaire studies that have been carried out, allowed the patients to be divided into two groups: women who do not smoke and are not exposed to ETS (17 women), and the ones who smoke (14 women). The women who smoked 11-15 cigarettes a day and more than 16 cigarettes constituted the largest percentage. The conformance of the declaration with the real exposure to tobacco smoke within the group of non-smoking women was 88%. Within the group of non-smoking women, the level of cotinine in 15 cases was 0 ng/ mg of creatinine, whereas in two cases, it amounted to 19.4 and 215.4 ng/mg of creatinine respectively. Among the persons, who were smoking, there were 4 cases, where the biomarker's level was 0 ng/mg of creatinine, and in 10 cases, the mean concentration of cotinine was 169.1 +/- 121.8 ng/mg of creatinine. The measurement of the content of tobacco specific N-nitrosamines (NNAL- metabolite of NNK) in the urine of pregnant woman was carried out by means of the liquid chromatography/tandem mass spectrometry (LC/MS/MS). The analysis of obtained results showed that the mean concentration of NNAL in urine of smoking women was 59.2 +/- 40.2 pg/ ml. In the case of two patients, who declared to be non-smokers, and in the case of whom, the presence of cotinine was detected (19.4 and 215.4 ng/mg of and 88.4 pg/ml. The presence of 4-(metylnitrosamino)-1-(3-pyridyl)-1-butanol in the mother's urine, speaks volumes for the possible risk of exposure of a foetus to the cancerogenic components of tobacco smoke. The applied LC/MS/ MS method of determination of NNAL in urine, which allows the quantity of several pg/ml of the smoker's urine to be determined, can be used to mark the biomarker of exposure to the tobacco specific N-nitrosamines. The lack of correlation between cotinine and NNAL concentration in urine, and the number of smoked cigarettes, speaks volumes for the lapse of quite a long time from the moment of cigarette smoking to the moment of collection of the biological material for research and the possible incredible declaration as to the number of smoked cigarettes. Only a slight tendency for the increase in the concentration of NNAL as well as the increase in the cotinine level could be caused by the difference in pharmacokinetic parameters of marked metabolites at the moment of smoking cessation. PMID- 17288187 TI - [Tobacco smoking related DNA and protein adducts and risk of degenerative diseases]. AB - Tobacco smoke contains many thousands of chemicals including a plethora of carcinogens. Most chemical carcinogens undergo metabolic activation leading to the formation of electrophilic metabolites. These highly reactive species interact with nucleophilic sites in DNA and cellular proteins. Thus as result of voluntary as well as passive tobacco smoking, the DNA and protein adducts are detected in human tissues and blood. Tobacco smoke induces also the oxidative DNA damage. This paper reviews the data indicating, that analysis of DNA and protein adducts provides mechanistic insight into association between tobacco smoke and neoplastic and degenerative diseases. PMID- 17288188 TI - [The quantitative evaluation of the serum acute phase proteins (APP) of patients undergoing a curative resection for non-small cell lung cancer (NSCLC)]. AB - The aim of this study was to quantitatively evaluate serum APP in patients undergoing the radical resection for NSCLC. The quantitative changes in APP were correlated with the cancer type, clinical staging and grading and the procedure type. Also, the impact of selected post-operative complications on the APP serum concentrations was evaluated. 46 patients undergoing surgery secondary to NSCLC in the years 2003-2004 were analyzed. The patients' age varied from 45 to 77 years with an average of 61.1. The most common pathological cancer type was the squamous cell cancer (24 patients) and adenocarcinoma (17 patients). The majority of the patients were stage IIB (15 patients) and IIIA (14 patients). The following APPs were evaluated in the patients' serum by Laurell rocket immunoelectrophoresis: C-reactive Protein (CRP), alfa-1 antichymotrypsine (alfa-1 ACT), alfa-1 antitrypsine (AT), alfa-2 macroglobuline (alfa2 M), ceruloplasmin (Cp), haptoglobine (Hp) and transferrin (Tf). Significantly higher serum AT level were found in patients with adenocarcinoma as compared to other pathology types. Patients with the squamous cell cancer had a significantly higher level of alfa-2 M and Cp. There was no significant difference in APP levels between the cancer grading types. In the group of patients with T3 or T4 stage the following five APPs were significantly elevated: CRP, AGP, alfa-1 ACT, alfa-2 M and Cp. Patients with regional lymph nodes metastasis (N2 or N2) had significantly higher level of AT, CRP and Hp. Patients undergoing more significant procedures (pneumonectomy, prolonged procedure time) and those with morbidities (rethoracotomy, blood transfusions) showed significantly higher levels of alfa-1 ACT, AGP and Cp. The most common post-operative complications were prolonged air-leak requiring probronchoscopy. In both complications a significantly higher level of AGP was observed. Patients with adenocarcinoma of the lung and regional lymph node metastasis have significantly higher serum levels of AT. This protein could be considered as one of the indicators of cancer involvement and could be a marker of the cancer recurrence. AGP is a protein that correlates positively with a more advanced clinical stage, and the extent of the surgical procedure as well as with the higher risk of morbidity. This could serve as a marker of higher post operative complication rate. PMID- 17288189 TI - [Immunohistochemical localization of p53 protein in smoking patients with chronic pancreatitis]. AB - Epidemiological studies show that smokers are at a significantly higher (70%) risk of getting affected by chronic pancreatitis and tumours of pancreas than non smokers. The aim of the study was to assess the effect of cigarette smoking on the expression of gene p53 in pancreas by defining immunohistochemical localization of p53 protein in tissue specimens of the pancreases derived from healthy persons and smoking and non-smoking patients with diagnosed chronic pancreatitis (CP). Patients underwent surgery in which tissue material was collected. Immunohistochemical localization of 53 protein in paraffin tissue specimens of the pancreas was performed using the LSAB2-HRP visual test (DAKO K0673) with monoclonal p53 protein (DAKO N1581) antibodies. Exposure to tobacco smoke was assessed by determining cotinine in the patients' serum using the ELISA method. The study revealed a expression of p53 protein in smoking CP patients. In non-smoking patients and healthy persons wasn't showed expression of protein. Smoking patients above the twenty cigarettes for day showed significantly higher expression of p53 protein in the pancreas compared to smoking patients less. Cigarette smoking increases the expression p53 protein in pancreas of smoking patients with chronic pancreatitis. Impairment of the gene p53 in pancreas is frequently manifested by complications in pancreatitis resulting among others from long-term smoking, and conducted by tumour proliferation. PMID- 17288190 TI - [Influence of tobacco smoking on the level of alfafetoprotein and circuleting immune complexes in serum of smokinig and nonsmoking women being in second trimester of pregnancy]. AB - In Poland 35% of women, 25% of them being in reproductive age, smoke cigarettes. Substances included in tobacco smoke have highly toxic properties. Their presence in the human organizm may affect immunological mechanisms which are an important element determining dynamic balance betwen the mother and the fetus. The aim of the article is to compare the level of AFP and circulating immune complexes (KKI) concentrations in smoking and non smoking pregnant women in the second trimester. The levels of immunological complexes in the women's sera were determined by means of the Elisa immuno-enzymatic method using DRG Instruments GmbH Germany tests. The levels and the properties of circulating immune complexes were estimated in sera of 27 women being in the second trimester of pregnancy by means of polyethylene glycol (PEG) precipitation test. Molecular weight of the proteins of CIC was studied by SDS/PAGE. In the group of smoking women AFP levers were higher and KKI levels were lower than in the non smoking women group. PMID- 17288191 TI - [The influence of tobacco smoking on homocysteine and glutathione levels in biological samples]. AB - The aim of this paper was to examine the effect of tobacco smoking on the level of homocysteine and glutathione in biological samples. The study comprised 30 people, who qualified into two groups--subjects who never smoke the cigarettes (n = 10) and currently smoking (n = 20). Smoking habit were assessed by questionnaire. Cotinine (major metabolite of nicotine) was determined in urine using high-performance liquid chromatography method (HPLC) with ultraviolet detection. The biothiols: glutathione in reduced and oxidized forms and homocysteine were determined by HPLC method using coulometric electrochemical detection. The concentrations of total and free plasma homocysteine were higher in active smoker. Glutathione levels in both groups were comparable. Observed differences should be explained in the further experiment. PMID- 17288192 TI - [In patients with coronary artery disease and left ventricular contractile insufficiency the pathogenicity of smoking associates with imbalance in metabolism of homocysteine]. AB - Development of the systolic left ventricular insufficiency in patients with coronary artery disease (CAD) markedly decreases the survival rates, so the factors affecting the clinical status of these patients should be reevaluated. The left ventricular contractile function has been assessed by measurements of the left ventricular ejection fraction (LVEF) values. The studied group of 160 males comprised 102 CAD patients diagnosed by coronarography, and 58 persons without CAD and left ventricular systolic insufficiency. The CAD patients were divided into 2 subgroups according to the LVEF values: 53 patients qualified to have normal left ventricular contractile function (with LVEF > 40%), and 49 patients, with LVEF < or = 40%, were considered as subgroup with the left ventricular contractile insufficiency. In the case-control set up the effects of smoking, concentrations of homocysteine (Hcy) and folic acid (FA) and of the known risk factors of the vascular diseases in the development of the left ventricular contractile insufficiency were assessed. Moreover, analysis was performed of the association between LV insufficiency and the statin therapy and the number of infarcts. LV insufficiency in CAD patients associated with increased diastolic pressure (p = 0.006) and with increased uric acid concentrations in plasma (p = 0.02). The smoking, decrease in HDL-C and increased index TC/HDLC were the risk factors of CAD, independent of the LV insufficiency. In comparison to the CAD patients with the preserved systolic function, in the group of CAD patients with LV systolic insufficiency, more persons had recurrent infarcts (34.7% vs. 5.7%), and less persons had no infarct (8.2% vs. 20.8%, p < 0.05). In CAD patients with LV systolic insufficiency smoking associated with the higher values of HC/FA index (p = 0.01), younger age of the patients (p = 0.01), the number of persons not treated with statins (0.01) and the number of persons not having had heart infarct before (p < 0.05). These findings confirm both the effects of infarcts on the development of LV insufficiency, and the presumed association between the pathogenicity of smoking in LV insufficiency and the unbalanced metabolism of Hcy. The straight of the effect of smoking on the development of LV insufficiency in susceptible persons is shown also by the findings of the younger age of the smoking CAD patients as compared to the nonsmoking patients with LV insufficiency. PMID- 17288193 TI - [Evaluation of plasma endothelin-1 concentration in tobacco smoking patients with essential hypertension]. AB - An evident influence of nicotine on vasoconstrictive and mitogenic peptide-- endothelin-1 (ET-1) synthesis and expression of its receptors was observed in experimental investigations. The aim of this study was ET-1 concentration assessment in patients with essential arterial hypertension, regarding nicotine action as ET-1 production stimulant. The investigation enrolled 27 patients with essential hypertension (degree I and II). This group was divided into 2 subgroups: A--11 tobacco smokers and B--16 non-smokers. Both subgroups did not differ as for basic laboratory investigations. Smokers had considerably higher ET 1 concentration than non-smokers. These results may be explained by presented in this paper mechanisms of nicotine on ET-1 influence. Thus smoking cessation in hypertensive patients is very important also because of interactions mentioned above. PMID- 17288194 TI - [The influence of smoking on plasma non-enzymatic antioxidant concentrations in active smokers (preliminary report)]. AB - Tobacco smoke contains many reactive oxygen species (ROS) that cause oxidative stress. Crucial role in defending the organism against ROS play vitamins E and A. The aim of the study was to investigate the influence of tobacco smoke on concentration of main ingredients of these vitamins alpha-tocopherol and gamma tocopherol, as well as retinol. The study population consisted of 104 healthy males between the age of 34 and 45 years. Survey questionnaire and determination of plasma cotinine concentration were used to divide the group into smokers (62 males) and non-smokers (42 males). The arbitrary threshold value of plasma cotinine concentration was set to 15 ng/ml. High performance liquid chromatography (HPLC) was used to estimate the plasma concentration of alpha- and gamma-tocopherol, retinol and cotinine. Within the smoking part of the study population a significantly lower (by 12.5%) concentration of alpha-tocopherol, and non-significantly higher (by 15.7%) concentration of gamma-tocopherol was ascertained, when compared to the plasma concentration of those compounds in the non-smoking group. Practically no difference in concentration of retinol was found between the two studied groups. In order to determine the magnitude of interdependency between the extensiveness of exposure to tobacco smoke and the concentration of analyzed antioxidants, correlations between their plasma concentrations and plasma concentration of cotinine were investigated. A significant, moderate and negative correlation of alpha-tocopherol versus cotinin was determined, in the smoking group as well as in the entire study population (r = -0.291 and r = - 0,317, respectively). Other relationship: gamma-tocopherol versus cotinine and retinol versus cotinine did not show any correlation. The obtained results suggest that tobacco smoke weakens the organism's antioxidant barrier by decreasing the concentration of plasma alpha-tocopherol, while not influencing significantly the plasma concentration of gamma-tocopherol and retinol. PMID- 17288195 TI - [The effect of tobacco smoking during pregnancy on concentration of vitamin A and beta-carotene in matched-maternal cord pairs]. AB - Tobacco smoking causes oxidant stress in pregnant women and may have a similar effect in fetus. Vitamin A and beta-carotene are natural factors protecting cells from damaging influence of free oxygen species.Therefore the aim of the study was to estimate the effect of tobacco smoking during pregnancy on concentration of vitamin A and beta-carotene in blood of mother and newborn. Healthy women in III trimester of pregnancy were divided into non-smoking (n = 40) and smoking group (n = 35) according to the concentration of cotinine in serum and urine. Level of carotenoids was measured by HPLC (high pressure liquid chromatography) method in plasma of matched-maternal cord pairs. We observed that, in smoking women group concentration of vitamin A was lower in plasma of mothers as well as in cord blood of newborn (p < 0.001) and amounted respectively only 80% and 70% of that observed in non-smoking mother and their child. In smoking group plasma level of beta-carotene was significantly lower (by 30%; p < 0.0001) as compared with non smoking matched-maternal cord pairs. Plasma level of vitamin A was significantly correlated with concentration of pcarotene both in smoking and non-smoking pregnant women (r = 0.70, p < 0.001; r = 0.57, p < 0.001). The similar correlation was observed in umbilical cord blood in both groups (r = 0.81 and r = 0.82; p < 0.001). Reduced concentration of vitamin A and beta-carotene in matched maternal cord pairs suggest that consumption of this antioxidant for neutralization of free radicals present in cigarette smoking is enhanced. PMID- 17288196 TI - [Activities of superoxide dismutase, catalase, glutathione peroxidase and reductase in umbilical cord blood of newborns from mothers smoking during pregnancy]. AB - In pregancy complicated by cigarette smoking prooxidant-antioxidant imbalance may have a pathomorphological and pathophysiological effect in fetus. Efficient enzymatic antioxidant systems are natural factors protecting cells from damaging by free oxygen species. Therefore the aim of the study was to estimate the effect of tobacco smoking during pregnancy on activities of superoxide dismutase, catalase, glutathione peroxidase and reductase in umbilical cord blood of newborns. Healthy matched-maternal cord pairs (65) were divided into non-smoking (n = 35) and smoking group (n = 30) according to the concentration of cotinine in serum and urine. We observed that, in umbilical cord blood from newborns of smoking women activities of catalase, glutathione peroxidase and reductase were lower by 30%, 15% and 37% respectively than in non-smoking. The differences were statistically significant (p < 0.0001; p < 0.01; p < 0.0001). Activity of superoxide dismutase was similar in both studied group. In erythrocytes of newborns from smoking mothers activity of superoxide dismutase was significantly correlated with concentration of cotinine (r = 0.61; p < 0.01). The similar correlation was not observed in red blood cells of non-smoking ones. Our results indicate that tobacco smoking during pregnancy may have a negative effect on enzymatic antioxidant systems in umbilical cord blood. PMID- 17288197 TI - [The comparison of ascorbic acid concentration in smokers with diabetes mellitus type II scheduled for coronary artery bypass grafting (CABG) to ascorbic acid concentration during postoperative and convalescence period]. AB - Cardiovascular disease is the main cause of increased mortality in diabetes patients. Myocardial infraction and stroke is in 60% to 80% causes reason of death in patients with type 2 diabetes mellitus. The main risk factor of cardiovascular disease is hyper-glycemia, hyperinsulinaemia and hypertension. The other arteriosclerosis risk factors are for example smoking. We measure the concentration of ascorbic acid in smokers' diabetes patients with type 2 diabetes mellitus with stable coronary disease scheduled for coronary artery bypass grafting (CABG). Vitamin C is assumed to be a basic antioxidant although its role in pathological conditions is controversial. However, it seems that the complexity of the oxidant-antioxidant system makes the question of participation of ascorbic acid in pathogenesis of diseases still open. Determination of the role of ascorbic acid concentration in pathogenesis of diabetic angiopathy may be of significant importance in the their effective therapy. PMID- 17288198 TI - [The influence of tobacco smoke on plasma atherogenic compounds levels in active smokers (preliminary report)]. AB - The aim of the study was to evaluate the influence of tobacco smoke on plasma concentration of atherogenic compounds, namely total homocysteine (tHcy), symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). The study population consisted of 104 healthy males between the age of 34 and 45 years. Survey questionnaire and determination of plasma cotinine concentration were used to divide the group into smokers (62 males) and non-smokers (42 males). The arbitrary threshold value of plasma cotinine concentration was set to 15 ng/ml. High performance liquid chromatography (HPLC) was used to estimate the plasma concentration of tHcy, ADMA, SDMA and cotinine. Significantly higher (by 38.5%) plasma concentration of tHcy in the group of active smokers in comparison with non-smokers was observed. The concentration of ADMA and SDMA was found out to be higher by 12.8% and 13.5% respectively, however those differences were highly non-significant. Positive significant correlation between concentration of tHcy and cotinine was determined, in the smoking group as well as in the entire study population (r = 0.303, P = 0.017; r 0.257, P = 0.009 respectively). There was no evidence, however, of correlation between the concentration of both ADMA and SDMA and cotinine. Correlation between the concentrations of atherogenic parameters showed weak but significant correlations for tHcy versus ADMA and tHcy versus SDMA and high for the ADMA versus SDMA correlations (r = 0.671 in the smoking group and r = 0.672 in the entire population). The results obtained indicate that tobacco smoke probably has a weak influence on smokers' plasma ADMA and SDMA concentration, while significant rising the concentration of homocysteine, an independent risk factor of atherosclerosis. PMID- 17288199 TI - [The influence of tobacco smoking on the lead and cadmium concentration in the urine of pregnant women and the health state of newborn]. AB - The purpose of the study was to measure the concentration of lead and cadmium in urine of women who smoked, were exposed to environmental tobacco smoke (ETS) and were unexposed during pregnancy. The correlations between exposition to tobacco smoke and socioeconomic factors, course of pregnancy and health status of newborns were estimated. The subjects of the study were 231 pregnant women. Information about exposition to tobacco smoke, socioeconomic state, course of pregnancy and health status of newborns was collected from self-created questionnaire. The estimation of tobacco smoke exposition of the women was based on the questionnaire data and their urine cotinine concentration. The urine concentration of lead and cadmium was measured by atomic absorption spectrometry with graphite furnace. The mean urine lead concentration of women who smoked, were exposed to ETS and unexposed to tobacco smoke during pregnancy were respectively: 38.2 +/- 59.1; 36.2 +/- 50.1; 32.7 +/- 53.5 ng/ mg of creatinine, and mean cadmium concentration were respectively: 1.9 +/- 1.6; 1.1 +/- 1.2; 1.3 +/- 1.5 ng/mg of creatinine. The correlation between the urine concentration of cadmium and cotinine was statistically significant. Increased frequency of tobacco smoking was in the group of the women aged less than 25 years, that finished primary or vocational school, had monthly income less tan 500 zl/family member, and have smoking partners. In the group of women who smoked during pregnancy the childbirth was statistically more often by caesarian and supported delivery. The newborns of mothers who smoked and were exposed to ETS had birth weight respectively 348.5 g and 281.1 g smaller than newborns of unexposed mothers. The length of newborns of smoking and ETS exposed mothers were respectively 2.8 cm and 0.7 cm shorter then newborns of unexposed mothers. PMID- 17288200 TI - [Smoking influence on cadmium, lead, selenium and zinc level in placenta, cord blood and maternal blood of women at delivery from Gdansk region]. AB - Cadmium, lead, selenium and zinc levels were determined in placenta, maternal blood and cord blood of 53 women at delivery from Gdansk region. Non-smokers [NS], passive smokers [PS] and smokers [S] were identified by the questionnaire. Our results suggest that there is no smoking impact on the levels of determined elements in placenta. Smoking women have higher Cd and Pb blood levels than mothers who never smoked (p < 0.01). Selenium levels in maternal and cord blood were higher in non-smoking group than in smokers (maternal blood NS vs S p < 0.01; cord blood NS vs S p < 0.001), but there is no smoking impact on the zinc levels in the study tissues. We also investigated the negative influence of tobacco smoke exposure on the distribution of the micro-elements in the feto placental unit and that the ratio of Zn/Cd and Se/ Pb is higher in all tissues of non-smoking than smoking women. PMID- 17288201 TI - [Determination of cadmium level in passive tobacco smokers schizophrenia patients]. AB - Schizophrenia is a long-term illness which concerns 1.4% of human population. It has been known as periodical or continuous, emotional or social disorder and it could cause substantial mental disability often leading to suicidal behavior or various other life threatening situations. Schizophrenic patients can not be classified as a homogenous group. The differences are caused by various psychopathological symptoms, different course of illness and different reactions to neuroleptic drugs among patients. Often these differences as well as connections with patients characteristics and symptoms of illness suggest the common name to the illness as "schizophrenia group" which includes mental illness of various etiopatogenesis and different psychobiological basis. Schizophrenia patients belong to the group of highest level of dependency on nicotine. It has been found that dependency on nicotine in this group is 1.5-2 times higher than in general population. Modern pharmacology started in 1952 when chlorpromazine was given for the first time to the mentally ill patients in St. Anne hospital in Paris. This breakthrough allowed mentally ill patients keep on undertaking treatments outside the hospital. The possibility of getting significant improvement in treatment of incurable, until now, illness paved the way for changes in general opinion about mental illness, particularly schizophrenia. Derivate of phenothiazine have been the oldest and most frequently used psychotropic drugs in Poland. They belong to the most numerous group of heterocyclic organic compounds which contains an aromatic triple-ring complex with atoms of sulfur and nitrogen. Therapeutic monitoring of drugs started at the end of sixties. Necessity of individualization of drugs in order to keep effectiveness and safety on proper level was an immediate answer to differences in intensity of pharmacological reaction to the drugs dosages among patients. Therapeutic monitoring is a method which anticipates a certain model of treatment depending on the results of clinical and pharmacological medical research. Therapy monitored by concentration of drug (TDM) is a mean to conduct therapy simultaneously with measuring concentration of drug in biological fluid. The results of lab research directly influence the dosages of drug. PMID- 17288202 TI - [Effect of passive smoking on the level of selected metals in deciduous teeth]. AB - The cigarette smoke is a significant source of heavy metals, which after being absorbed into the human organism, may be accumulated in a calcified tissue. The accumulation process may be also a result of a passive exposure to the cigarette smoke. As the hard tissues of deciduous teeth are relatively stable in chemical composition, they are widely used as the indicators of the exposure to heavy metals in children. This project is aimed to estimate the effect of passive smoke on the levels of selected toxic and essential elements in deciduous teeth. The research material consisted of 386 deciduous teeth. Out of this, 205 teeth were from the children exposed to the cigarette smoke in the apartments. The levels of cadmium, copper, iron, manganese, lead, zinc, calcium and magnesium were determined using atomic absorption spectrometer with flame atomization. It was concluded that the exposure to the cigarette smoke in children is a factor producing the changes in the levels of selected toxic and essential elements in deciduous teeth. This particularly results in the higher levels of cadmium, copper, lead and zinc, which are the permanent constituents of the cigarette smoke, and the lower levels of manganese, calcium and magnesium. Moreover, the disturbed gradient of lead levels dependent on the tooth type is observed in the children exposed to the cigarette smoke in the apartments. PMID- 17288203 TI - [Aluminum in hydroxyapatites of gallstones from smoking and non smoking women]. AB - The investigation on the aluminum changes in gallstones from 149 women, including 49 smokers and 79 non-smokers women was carried out. All patients were inhabitants of Southern Poland. Aluminum concentration was determined using Inductively Coupled Plasma - Atomic Emission Spectroscopy (ICP-AES) with the measurement precision of 1-3% and the detectability of 0.01 microg/g. Arithmetical mean was statistically significantly higher for non-smoking women (33.39 microgAI/g) in comparison to smoking women (20.30 microgAI/g). The changes of given elements were different for smoking women in comparison to non-smoking women. PMID- 17288204 TI - [The changes of barium and strontium content in gallstones from smoking and non smoking women]. AB - The problem of statistical characteristics of occurrence barium and strontium content in gallstones from smoking and non-smoking women living in southern Poland is presented in the work. The subjects of the research were gallstones, gained intraoperatively from 146 women (49 smoking, 97 non-smoking). The content of barium and strontium was determined using atomic emission spectroscopy with inductive coupled plasma (ICP-AES). The statistical characteristic of barium and strontium content in gallstones shows that smoking does not decide about content level of these elements in gallstones. Content of barium (2.32 microgBa/g) as well as strontium (3.23 microgSr/g) in gallstones from non smoking women are higher in comparison to content of these elements in gallstones from smoking women (1.91 microgBa/g and 2.76 microgSr/g). PMID- 17288205 TI - [Analysis of participation of mercury in gallstones from smoking and non smoking people]. AB - Mercury concentration in gallstones of 146 women (49 smoking, 97 non-smoking) and 24 men (11 smoking, 13 non-smoking) was determined employing Inductively Coupled Plasma - Atomic Emission Spectroscopy (ICP-AES). The possibility of mercury accumulation in concretions in the gallbladder was confirmed by the study. The changes of given elements were different in comparison for smoking and non smoking women and men. The research of mercury occurrence in gallstones shows the presence of higher concentration at smoking both women (0.16 microgHg/g) and men (0.22 microgHg/g) in comparison to non smoking women (0.12 microgHg/g) and men (0.06 microgHg/g). PMID- 17288206 TI - [Metabolism of chromium in femur head in aspect of cigarette smoking]. AB - The objective of this study was qualification of content chromium in femur head in aspect of smoking cigarette. Investigated of femur head from habitants of Upper Silesian Region. The content of chromium was marked at non-smoking persons, smoking in past and smoking at present. Determination of contents chromium realized by ASA method (Pye Unicam SP-9) in flame acetylene-oxygen. Higher contents of chromium were observed for smoking people. The most of the correlations described by large values of the correlation factors were concerned Cr with Ni, Cu, Zn, Na. PMID- 17288207 TI - [The assessment of toxic components from tobacco/ smoke in working students]. AB - The aim of presented study was to assess the basic toxic components intake by working students. The questionnaire study was curried out on 82 students (52 women and 30 men) aged 26 +/- 6 years. However, the percentage of non-smokers in the studying group was 71 (61% of women and 87% of men), the approximately 90% of both analyzing sub-populations: non-smokers and smokers, rank themselves among passive smokers with accompanying of other smokers by mean 2,3 +/- 2,0 hours per day. The estimating daily toxic components intake in active and passive smoker groups, were following respectively: nicotine--4.9 +/- 3.4 vs. 2.0 +/- 1.5; tar- 60.3 +/- 42.0 vs. 24.4 +/- 18.0; carbon monoxide--62.4 +/- 43.5 vs. 25.2 +/- 18.7 mg/day. In conclusions, the non-smokers are exposed on toxic components of tobacco smoke in the half parts of these what smokers intake. PMID- 17288208 TI - [Does second-hand smoking get children's and adolescents' quality of life worse?]. AB - The aim of the study was to evaluate the relationship between second-hand smoking and health-related quality of life in children and adolescents (HRQL). Data was obtained through KIDSCREEN survey conducted in Poland in 2003. The subsample of 1045 school-children aged 10-16 yrs was selected. HRQL was measured by KIDSCREEN 27 child version indexed in five domains. Results showed that 48.4% of school children lives with at least one parent smoking at all, and 15.5% with both parents smoking every day. About 80% of smoking parents reported smoking in the presence of child, while 44% at least often. Overall, 22% of adolescents at this age are at high risk of second-hand smoking because of parental behaviors. Children having parents smoking on the regular basis reported lower quality of life, especially in the domain describing family and school environment. Multivariate linear regression models indicated that smoking by mother is the most important predictor of low HRQL. Parental smoking could be recognized as social determinant of low HRQL, in some domains even more evident than lower parental education level. PMID- 17288209 TI - [The phenomenon of spreading smoking cigarettes among the first year course students in the Medical Academy]. AB - The World Health Organization declared the addiction of tobacco smoking as a separate disease unit requiring adequate recognition and treatment. In the International Classification of Diseases, it has been registered with F17 as mental and behavioral disorders caused by tobacco smoking. As some research shows, an estimated 4 million people die every year (about 11 thousand a day), because of smoking-related illnesses and the number has been expected to rise until 10 million in 2030. The health service workers such as nurses and midwives play a huge part in establishing pro-health attitudes. They are expected to participate in campaigns promoting a tobacco-free lifestyle. It is important that the persons mentioned were non-smokers, otherwise the information regarding the negative effects will be unconvincing. The main goal of the study was to estimate the phenomenon of spreading smoking cigarettes among the first year course students in the Medical Academy, and accomplishing their knowledge and awareness about threats resulting from tobacco smoking. All information was collected from the poll questionnaire, which was filled in by each person independently. The group (n = 100) consisted of 50 interviewed females (n = 50) and 50 interviewed males (n = 50) at the age between 18 and 20. The poll questions were carried among the first year course students in the Medical Academy, in May and June 2006. They were guaranteed anonymity. The results subdued to statistic analysis showed no statistic dependence between the gender of the interviewed and tobacco smoking. The basic study questions referred to the number of young people who have already experienced smoking, and to the intensity degree of the experience. The study aimed also in identifying factors influencing the popularity of the phenomenon in question. The research touched such questions as conviction about damage caused by smoking, the source of information, causes and effects of smoking, about the environment of the interviewed people (family members, friends -whether they are smokers or non-smokers). Other questions concerned the time of the first experience with smoking- whether it was childhood, puberty or adolescence time, the interviewee's smoking preventive activities in their future work place and their opinion about themselves as non-smokers. All the questions were subdued to quantitative measurement due to estimation of all interviewed population. PMID- 17288210 TI - [Tobacco smoking among students]. AB - Tobacco smoking is accompanying people for many years. Last century it accompanied inseparable not only adult part of our society--3 of young people smoked. They attempted one or many times to smoke, and this way they often started regular smoking. The aim of this study was analysis of spread of tobacco smoking among 90 first year midwifery students. The study was conducted in the University of Medical Sciences in Poznan. The questionnaire included 13 questions, The Fagerstom- and the Schneider-Tests. The results show that only 3 (3.33%) persons regularly smoke cigarettes. Most of the students are conscious (aware) of threat of nicotine dependence. PMID- 17288211 TI - [Attitudes and behaviour concerning cigarette smoking among the students of the first year at the Health Department]. AB - Smoking is still very common in Poland. Our country is among the leading countries with the greatest consumption of cigarettes. It is estimated that currently, there are about 40% smokers among men and 20% among women. In the future, most of the graduates from the Health Department will take care of the promotion of healthy life style and health education in the society. It is important that their theoretical knowledge be supported by proper health bases. A health centre worker who is inhaling smoke and at the same time encouraging quitting smoking is by no means credible. The aim of this work was to establish the participation of those students who are inhaling tobacco smoke that is among the students of the three departments of daily students of the Health Department. There were 108 female students who underwent the survey among the first year students of the Heath Department of Medical University of Lodz. The tool used was a survey. In the research carried out between 1st and 15th March 2006, 104 students (96.3%) took part. Among those who handed the surveys back, there were 32 males (30.8%) and 72 women (69.2%). In the group of respondents, which included 104 people, 33 (31.7%) stated that in January and February 2006 smoked cigarettes and 71 people (68.3%) claimed that within that time they did not smoke a single cigarette. Among the smokers, there were 11 males (f = 0.33) and 22 women (f = 0.67), whereas in the non-smokers' group, there were 21 male students (f = 0.30) and 50 female students (f = 0.70). In the past, there were 55 surveyed who inhaled tobacco smoke (52.9%), whereas 49 surveyed (47.1%) stated that they had never smoked in the past. In the smokers' group, there were 18 male students (f = 0.30) and 37 female students (f = 0.70). Among those who claimed they had never smoked before, there were 14 male students (f = 0.30) and 35 female students studies of the Health Department of Medical University of Lodz inhaled tobacco smoke. In comparison with the studies carried out at other universities in Poland, the received result in the worst. It is necessary to undertake actions that would lead to some changes in the behaviour of the students of the first year of Heath Department in order to achieve the greatest possible ratio of non smokers before their graduation. PMID- 17288212 TI - [Students of midwifery and nicotine dependence]. AB - Tobacco smoking is one of the principal public health problems. Therefore, at present, many new methods of prevention are being introduced. That is why education programs in Universities of Medical Sciences are very important. The aim of the study was to evaluate tobacco smoking among students of Midwifery. The study was performed among 73 students. They answered 16 questions concerning smoking and knowledge about nicotine dependence. PMID- 17288213 TI - [Students of nursing and nicotine dependence]. AB - Tobacco smoking is a significant part of life stile and the factor, which determinates state of health in a high rate. It is a very important social problem in Poland, because in spite of relative extensive knowledge about tobacco influence on bio-, psycho-, socio-well being, percentage of smokers is still high. These remarks should lead to creation "the fashion of no smoking" among future health care workers. According to organized activity cycle in the first stage this research we decided to diagnose the environment of the students and then to plane and implement health promotion and disease prevention activities, and finally evaluate them. The aim of the study was to analyze tobacco smoking among students of Nursing. The problems concerned level of dependence, readiness to stop smoking and knowledge about harmfulness of nicotine. PMID- 17288214 TI - [Problems in tobacco smoking in opinion of VI year of medical students]. AB - The aim of our study was the evaluation of tobacco smoking among students of VI year of Medical University of Gdansk. Anonymous questionnaire was done among one hundred and ten students including 70 women and 40 men in the age from 23 to 29 (24.82 +/- 1.03) years. CONCLUSIONS: 1. There were 12.7% of daily smoking students including 8.6% women and 15% men. 2. Almost 79% volunteers ineffectively attempted to give up smoking within last year. 3. The smoking students abused alcohol (with high likelihood) and used recreational drugs twice more than nonsmoking colleagues. 4. Almost all volunteers (96.4%) want to use smoking cessation intervention in their patients. 5. Above 75% students declared to broaden their knowledge about diagnostic and smoking cessation therapy. PMID- 17288215 TI - [Internal locus of control of health and smoking cigarettes in young adults]. AB - Disturbances connected with nicotine lead to abuse on physical and psychological level, they are the reason of harm in individual and global perspective as well. They may be a reason of behavioural disturbances additionally. The aim of the study was to estimate the locus of health control in young adults-- students of Poznan University of Medical Sciences. Forty-six students aged 20-39 yrs. of age smoking and non-smoking participated in the study. MHLC Scale and questionnaire of own idea used in the study. Hypothesis verified with the statistical analysis test T, correlation analysis with help of SPSS program. The significance level p = 0.05 was stated as significant. The results show that most of students have internal locus of health control. The conclusion stated independently from the factor of smoking cigarettes. Respondents with smoking habits underline the influence of chance on health as well. The results confirm the data from the research studies in population of the students. The hypothesis on the lower level of internal control in people with smoking habits did not confirm in the study. However MHLC estimates as good tool for the estimation of the internal factors determining activities for health. PMID- 17288216 TI - [Tobacco smoking and psychoactive substances use among students--a preliminary report]. AB - Tobaccos smoking, and psychoactive substances use in the student environment, both legal and illegal, have always come with many controversies. The problem extent have appeared as much bigger then it had been previously thought and now it affects all social and professional communities. In the research, authors have centered on medical students to assess their knowledge, attitudes and awareness of the problem and not only analyze the problem dimension. This is very important because of their further professional attitude to those problems, and their behaviors that have been created during the studies and will have an impact on perception of phenomena that appear in health of the public. PMID- 17288217 TI - [Smoking and drug use among students of selected univerities]. AB - Smoking, drinking alcohol and drugs are still actual social and health problems in Poland and in the world as well. Conducted studies, considering health behaviours among children and youth, indicate high percentage (between 20-30%) of smokers in mentioned population, depending on age, gender and environment. Health effects caused by smoking occur usually in adulthood as smoking related diseases, despite the addiction leading to the health problem begins earlier, even in childhood. Statistics, considering drinking alcohol and drugs abuse among young people are also frightening. The aim of the study was to evaluate and compare the state of knowledge about harmful effects of smoking, drinking alcohol and drugs use among students of Silesian Medical University, Silesian University of Technology and Academy of Physical Education and to evaluate and compare health attitudes towards mentioned addictions among students of different Universities. 315 students at age between 19-24 years took part in the study and filled in the anonymous questionnaire prepared by authors. Surveyed population included 108 students of Silesian Medical University, 110 students of Silesian University of Technology and 97 students of Academy of Physical Education in Katowice. Knowledge, presented by all students, about harmful effects of smoking, drinking alcohol and drugs use is not put into practice and does not result in healthy behaviours in examined part of life style. Students of Silesian Medical University demonstrate the highest state of knowledge about drugs. Students of Academy of Physical Education in Katowice have the most improper behaviours in the area of addictions. There is a necessity of preparing and spreading efficacious prophylactic programmes in order to raise awareness about the harmfulness of smoking, drinking and drugs use. PMID- 17288218 TI - [Smoking prevalence during pregnancy and exposition of infants to environmental tobacco smoke]. AB - Harmful influence of tobacco smoke on mother and child comprises many effects, among which the best known are: impaired fecundability, increased risk of pregnancy and perinatal period complications, increased morbidity of neonates and respiratory, circulatory and neurological disorders in neonates, infants and older children. The aim of this study was to assess smoking prevalence among pregnant women and young mothers and to assess the degree of exposition of infants to environmental tobacco smoke (ETS). The study was carried out among 74 women after delivery in the F. Raszeja City Hospital in Poznan, Poland, between December 2005 and May 2006. Smoking prevalence among pregnant women was 8.1% (women with high educational level--2.6%, others--14.3%). Smoking prevalence among mothers within the first year after delivery was 4.05% (women with high educational level--0%, others--8.6%). 17.6% infants (10.3% children of mothers with high educational level and 25.7% children delivered by the other mothers) were exposed to ETS because of smokers at home (other than mother); 10 infants exposed to ETS had non-smoking mother. PMID- 17288219 TI - [Tobacco smoking among patients from outpatient clinic of Institute of Cardiology]. AB - Smoking is well-recognized risk factor for heart diseases. The aim of a study was to evaluate incidence of smoking among patients of Outpatient Department of Institute of Cardiology. A questionnaire was given to 53 randomly chosen patients. Smoking and health habits were main questions asked. There was statistically significant correlation between age and profession and smoking. In this small group of patients with frequent contacts with medical profession health promotion was insufficient to eliminate smoking completely. PMID- 17288220 TI - [Evaluation of quality of life and knowledge about tobacco smoking toxicity among patients hospitalized in Department of Pneumonology]. AB - The aim of the study was to evaluate knowledge about tobacco toxicity among patients hospitalized in Department of Internal Diseases, Pneumonology and Allergology in Warsaw and to examine their quality of life. The study comprised 51 people at age between 18-80 years, from Warsaw and its environs. They were hospitalized because of many reasons like: COPD or asthma exacerbation, cough and focal pulmonary lesions diagnostics, follow-up examinations because of sarcoidosis or pulmonary fibrosis. Data for analysis were achieved from anonymous questionnaire prepared by authors and filled by patients. Quality of life was assessed with EQ-5D Questionnaire. The tobacco addiction rate was assessed with the Fagerstrom questionnaire, and the motivation to quit smoking with the Schneider test. It was found that only 14% of hospitalized patients have never smoked cigarettes, 86% smoked in the past, and 29% declare regularly smoking in present. The most common pointed tobacco-related diseases were lung cancer and hearth diseases. People hospitalized because of COPD exacerbation (CHPOChP) had significantly lower level of quality of life than patients hospitalized because of asthma exacerbation (CHA) (p = 0.03), and this both groups had significantly lower level of quality of life than persons without obstructive pulmonary diseases (NCH) (NCH - CHPOChP p = 0.0004; NCH - CHA p = 0.04). The motivation to quit smoking in COPD smokers group was significantly lower than in group treated in the hospital because of other reasons (p = 0.004). PMID- 17288221 TI - [Smoking addiction and patients' motivation to quit it among attenders of the Saldent 2006 conference]. AB - This paper presents the results of a survey carried out among those attending the Saldent 2006 conference. The questionnaire used for this purpose included questions concerning smoking among dentists, permission to smoke in the dental surgery, patients motivation to quit smoking, knowledge regarding the harmful effect of smoking on the oral cavity and the possible need for teaching preventive measures on the subject during under- and postgraduate education. The results showed that when compared with those obtained 6 years ago smoking among the dentists has declined. Answers to the questions concerning the influence of smoking on oral cavity showed a high awareness of this danger among the questionnaire respondents. Also the high number of dentists who are motivating patients against smoking confirms the opinion that in the planning of antismoking programs dentists can play a significant role. PMID- 17288222 TI - [Smoking of the tobacco by the parents of hospitalized children at the Pediatric Department of the Provincional Hospital in Opole]. AB - Nonsmoking children who live with smoking parents are exposed to many harmful chemicals of cigarette smoke. This situation is called "passive smoking". Unfortunately this situation is very often because 25% women and 40% men smoke. Cigarette smoke has bad effect on respiratory mucous membrane because it destroys its histological structure. Result of epidemiological studies provides that 45% parents and 54% children in pulmonological departments of pediatric hospitals are passive smokers. This indicates the necessity of pro-health education as well as the necessity of banning smoking from hospital area. PMID- 17288223 TI - [Anti-nicotine education applied in relation of parents of the diseased children on chronic allergic diseases of respiratory system]. AB - The allergies of respiratory system are at children the frequent illnesses. Among favorable them factors, risk on passive smoking tobacco can be also. Passive smoking is defined as risk non-smoking on tobacco smoke in environment. Recent reports represent that smoking in home environment tobacco increase on passive smokers' asthma morbidity, especially children in school age. It in it was report the necessity of leadership of anti-nicotine education was underlined in the face of smoking parents. It bets that she should motivate she better parents to cessation smoking, using authority of doctor and love parental. Acting we decided with these principles to analyze effectiveness two year anti-nicotine education which be applied in the face of all treated smoking parents of children with reason of chronic allergic diseases of respiratory system in out-patients. The study comprised parents of 146 children at the Allergy out-Patients clinic, who were diagnosed and cured in years 2003-2005. Generally were 292 persons. The children be treated with reason of bronchial asthma and allergic rhinitis. It the data on subject of smoking of tobacco were collected was on basis of interview got from parents during visits at information bureau on beginning the treatment the children, in his track as well as after two years of education. The anti nicotine education was applied by whole period of observation during routine medical visits. In moment beginning of treatment in studied group the parents' and education children (n = 292) it 79 the parents' couple did not smoke. Smoking parents among remaining 67 steams were. From among them parents 13 children smoked both, only father in 36 cases smoked and mother in remaining 18 parents' couple smoked. 80 parents smoked with generally. 63 persons after two years of anti-nicotine education the nonsmoking committed one from group smoking. 22 persons among them were from among 24 fathers and 17 mothers' peer in which smoked both parents. Remaining smoking and non-smoking parents granted that children tried to restrain to minimum stay in environment smoking. We on basis of received results to affirm that child's disease has on parents' behaviour essential influence can. It in child was affirmed was all analyzed situations characteristic decrease number with diseased child of smokers' families. Recapitulating anti-nicotine education of the children's parents diseased on chronic allergic diseases of respiratory system is very good restrictive agent their exposition on smoking the tobacco. Contemporaneously in effective way influences on decisions of adults about cessation smoking and the healthy style of life promotes. PMID- 17288224 TI - [The parents' awareness about threats for adolescents caused by tobacco smoking]. AB - Avoiding of children's and young people staying in smoky rooms and by adult people's consciousness of harmfulness of tobacco smoking is one of the most important factors affecting correct psychophysical development, physical activity, emotional state and mood of the young organism. The purpose of the paper was the estimation of consciousness of family, particularly parents, threats to the young organism caused by tobacco smoking by adult people and children's staying in the rooms full of the tobacco smoke. The group of 590 families of lower Silesian province dwellers, possessing basic, average and professional education was examined. A questionnaire was the basic research method, containing 25 of shut questions which parents were filling in. Obtained effects showed that parents who smoke cigarettes present the very low standard of knowledge for the subject of unfavourable consequences of the tobacco smoke on young organism development and functioning. PMID- 17288225 TI - [Economic status of smoking family]. AB - The tobacco smoking is a common phenomenon contributing not only to the occurrence of serious system diseases but before everything seriously depleting the budget of family. The paper presents the effects of the analysis of the material status of 605 families in which at least single one of its members is a habitual smoker. In examinations were participating only the lower-Silesian country provinces dwellers families' possessing basic, average and professional education. A questionnaire was the basic research method, containing 25 of shut questions was filled by accidentally present at home members of the family. Obtained effects showed that smokers' family were presenting the very low material status in the majority spending more than once around 1/3 of all one's monthly income (single persons) for cigarettes. However they are still lacking the motivation to discontinue smoking. PMID- 17288226 TI - [Preliminary analysis of smoking habit in firefighters of Wielkopolska region]. AB - Professional performance of firefighters causes high level of stress. This results in certain activities meant to lower a stress level, some of which are harmful to individuals health per se--smoking is a classical example here. This work was aimed at assessment of prevalence and style of smoking in the group of 69 professional firefighters of Wielkopolska region. Parameters studied were: prevalence, awareness of health-hazard, extent of nicotin addiction, motivation to quit with habit. Motivation to start smoking and further development of smoking habit as well as influence of environment was also studied. Since smoking presents a medical and social problem in this group of professionals, educative measures aimed at reduction of stress level and bad habit fighting should be undertaken. PMID- 17288227 TI - [Subjective and objective health status ex-smokers among elderly persons. CINDI WHO survey]. AB - Smoking tobacco increases the risk of numerous diseases as well as death due to tumours, cardiovascular and respiratory system diseases. It has been estimated that one of three smokers will die prematurely because of complications induced by smoking tobacco. Quitting smoking after turning 65 years old decreases the risk of chronic diseases and increases the estimated life expectancy. The aim of the research conducted within CINDI WHO Programme is exploring the influence of quitting smoking on subjective health perception and its objective condition among people of 65 and older depending on demographic and social factors as well as analysis of the reasons for quitting smoking by long-time tobacco smokers. The research included a group of 828 people of 65 years old and older living in an urban population. 10.7% of the senior citizen group were ex-smokers. Men more frequently than women quit smoking. A vast majority of ex-smokers (87.4%) quit before turning 65, however, 12.6% did it when they are above that age. The average age of quitting smoking was 45.9 +/- 15.8 years and the average smoking period was 26.9 +/- 15 years. The motivation for quitting smoking was mainly health reasons. Only 1/3 of ex-smokers assessed their health condition as poor or rather poor in spite of frequent risk factors such as hypertension, type 2 diabetes, obesity, lipid disorders. PMID- 17288228 TI - [How to decrease smoking among people? The experience of international anti tobacco campaign Quit&Win in Poland in 2000-2006]. AB - Findings imply the importance of smoking cessation at all ages, including those over the age of 65. Quitting reduces risks of dying from cardiovascular disease and several smoking-related cancers, improves mobility and quality of life among the elderly. Since 1994 all adult smokers over the world have been encouraged to quit by attending the Quit&Win contest, supported by WHO CINDI Program. The aim of our study was to analyze participation and effectiveness of quitting smoking among elderly (> or = 65 years) men and women in Poland. Data of Quit&Win contests from 2000 to 2006 in Poland among the elderly participants. One-year follow up survey of a random sample (640 respondents, response rate = 66%) in 2001. In Poland 508 elderly smokers have participated in Quit&Win from 2000 to 2006 (3.4% of 14.465 total number of participants). The oldest participants were more likely to be men than women (72% and 28% respectively), inhabitants of big cities than small towns or villages (66% and 34% respectively). Participants' history of smoking before the contest was as following: mean = 21 cigarettes/ day, higher consumption rates among elderly men than among elderly women (p < 0.05) and more years of smoking among men than among women (p < 0.001). The participants attended the contests sending press entry forms or printing entries mostly, but only 3% via the Internet. In one-year follow up the oldest participants were more likely than the younger participants: being the complete continuos abstains (p < 0.01), choosing the contest as a way of quitting (p < 0.001), having the support from family during their attempt to quit (p < 0.05). Attendance of the oldest smokers in Quit&Win is unsatisfied for organizers in Poland. To improve an access for the elderly the organizers, sponsors and media should maintain the traditional ways of entries distribution by newspapers and magazines. The Internet hasn't been popular so far among elderly people in Poland as a source of information and communication. Given the projected increase in the elderly population the medical and economic consequences of smoking will become a greater burden in the next decades. Therefore, focusing attention on cessation among the elderly is an immediate and urgent priority for public health professionals and physicians. PMID- 17288229 TI - [How often and how much have Polish centenarians smoked?]. AB - The data concerning tobacco smoking in the elderly subjects in Poland are spare and in case of the oldest individuals even unavailable. The aim of the study was to characterize it in polish centenarians. The study is the part of the multicenter centenarian program (PolStu 2001) coordinated by the International Institute of Molecular and Cellular Biology in Warsaw. In this paper we analyzed the information concerning tobacco smoking. In case of the answer YES for the question about smoking, the number of cigarettes smoked during whole life was calculated and expressed in pack-years (1 pack-year = smoking 20 cigarettes daily during 1 year). Among 336 analyzed centenarians 31 declared to have active exposure to tobacco. Men have declared to be smokers much more often than women (21 men 44.7% of all analyzed men and 10 women--3.5% of all women, p < 0.0001). During our analysis only 4 centenarians were still smokers, more often men tahn women (3 men--6.4% and 1 woman--0.3%, p < 0.005). The mean number of pack-years was 28.4 +/- 19.8 (median: 26.0; range: 1.0-90.0) per smoker. The mean number of pack-years was statistically higher in men than in women (33.8 +/- 18.0, median: 30.0, range 8.0-90.0 vs. 16.6 +/- 20.5, median: 10.5, range 1.0-63.0, p < 0.02). In conclusion, tobacco smoking in analyzed centenarians is rare phenomenon. However, almost one of ten centenarians declared to be smoker in the past. Tobacco smoking in our study was gender dependent--almost one of two men declared to be smoker in the past. PMID- 17288230 TI - [Alternative method of smoking cessation--reduce to stop]. AB - The new method of treatment of addiction to nicotine "Reduce to Stop" constitutes new possibilities of using the Nicotine Replacement Therapy (NRT). This type of therapy consisting in a significant restriction of the number of cigarettes smoked per day with a simultaneous taking of nicotine preparations constitutes a chance of giving up a habit for smokers who want to quit smoking, but cannot do it or are not ready for it. The clinical research confirmed the effectiveness of this method not only in restricting smoking, but also in increasing the motivation to stop smoking or even total giving up of the habit. PMID- 17288231 TI - [Smoking problem in developmental age]. AB - In this paper major health and psychosocial problems, including smoking habits, in children and adolescents in Poland are presented. Among other threats that accompanies nicotinism, diverse social pathologies depending on age, geographical region and economical conditions according to polish children from country and urban regions are discussed. Distant, negative influence caused by early onset of smoking on morbidity and mortality in adulthood is revealed. PMID- 17288232 TI - [New prospects of nicotine dependence treatment--vaccines]. AB - Smoking is considered to be one of the main threats to health in many societies around the world. Despite carrying out numerous large-scale campaigns promoting a healthy life-style and stimulant avoidance, nicotine dependence still concerns a huge group of people. What is more, almost half of the population is exposed to passive contact with tobacco smoke. At present, there is a whole range of pharmaceutical and non-pharmaceutical means of fighting nicotine dependence. The dramatic development of medical sciences in recent years, especially of the fields connected with biotechnology, resulted in working out of a new method of nicotinism treatment--antinicotinic vaccines. The starting point for working out of such drugs was the mechanism of nicotine action on central nervous system. The idea behind the vaccine is to prevent nicotine from passing through the blood brain barrier. Nicotine molecules, due to their size and lipophilic character, can easily enter the brain. The mechanism of the antinicotinic vaccine's action consists in producing specific antibodies, which combined with nicotine in the bloodstream are to create immune complexes big enough not to enter the brain. Currently, clinical trails of three vaccines are being carried out: TA-NIC (Xenova Group, UK), NicVAX (NABI Biopharmaceuticals, USA), CYT002-NicQb (Cytos Biotechnology, Switzerland). The results indicate that this form of treatment is interesting when it comes to its effectiveness and in the future may become a routine method of nicotine dependence treatment. PMID- 17288233 TI - [Problems of abuse of and dependence on Nicotine Replacement Therapy (NRT)]. AB - Smoking addiction consists in co-existence of pharmacological nicotine dependence and behavioral dependence. The most commonly used nicotine dependence pharmacotherapy is the Nicotine Replacement Therapy (NRT). At first, NRT preparations in many countries have been available on prescription only. Gradual introduction of NRT into over-the-counter sale involved the possibility of abuse. As a consequence, patients could become dependent on nicotine contained in the preparations, which are meant to be therapeutic. The analysis of results of current studies indicates that a small fraction of NRT patients (0.4-17%) uses it for a time longer than recommended. Thorough research assessing particular dependence symptoms do not, however, reveal such symptoms as: pleasure or satisfaction connected with taking the NRT preparations, subjective sense of dependence, difficulty in ceasing using NRT or occurrence of withdrawal symptoms. Thus, it has been suggested that NRT dependence occurs extremely rare is often times confused with chronic use. On the other hand, numerous studies show increased effectiveness of prolonged Nicotine Replacement Therapy, especially in heavy smokers. It is believed that a prolonged therapy using one NRT preparation does not pose any threat of severe side effects, just like simultaneous using of two NRT preparations or using NRT while continuing smoking. Conclusions drawn from current studies are reflected in the state-of-the-art guidelines concerning NRT use. PMID- 17288234 TI - [European experiences concerning schedules of the fight against the tobacco addiction]. AB - It was estimated that current cigarette smoking will cause about 450 million deaths worldwide in the next fifty years. Reducing current smoking by 50% would avoid 20 to 30 million premature deaths in the first quarter of the century and about 150 million in the second. Preventing young people from starting smoking would cut tobacco-related death but not until after 2050. Quitting by current smokers is therefore the only way in which tobacco-related mortality can be reduced in the medium-term. There is evidence that some form of treatment aids an increasing number of successful quit attempts. European experiences concerning schedules of the fight against the tobacco addiction with the use of the treatment aids were described in the paper. PMID- 17288235 TI - [The history of antitobacco actions in the last 500 years. part. 1. Non-medical actions]. AB - Tobacco was brought to Europe by Christopher Columbus, who discovered it in Cuba in October, 1492. Spread of tobacco consumption was initiated by the French diplomat Jean Nicot de Villemain, who in 1560 recommended it in the form of powdered tobacco leaves to the French Queen Catherine de Medice to combat her migraine headaches, and introduced the term Nicotiana tobaccum. Tobacco consumption greatly rose after the I World War, and after the II World War it became very common, especially among man. In the first half of the 20th century the sale of tobacco products rose by 61%, and cigarettes dominated the market of tobacco products. At the beginning of the 20th century cigarettes constituted only 2% of the total sale of tobacco products, while in the middle of the 20th century--more than 80%. Although the first epidemiological papers indicating that "smoking is connected with the shortening of life span" were published in the first half of the 20th century, not until 1950 did Hill and Doll in Great Britain, and Wynder and Graham in USA in 1951 show a statistically significant correlation between cigarettes smoking and lung cancer occurrence. Many controversies according the use of tobacco accompanied it from the beginning of its presence in Europe. The conflicting opinions according to its influence to health coexisted in the 16th to 19th centuries. In this period, especially in the 19th century dominated moral and religious arguments against tobacco. In the 20th century however, and particularly in its second part, development in medical research was enhanced by civil voluntary actions against advertisement and passive smoking. This lead to the significant limitation of tobacco expansion in Europe, USA and Canada in the end of the 20th century. PMID- 17288236 TI - [The history of antitobacco actions in the last 500 years. Part. II. Medical actions]. AB - Tobacco was brought to Europe by Christopher Columbus, who discovered it in Cuba in October, 1492. Spread of tobacco consumption was initiated by the French diplomat Jean Nicot de Villemain, who in 1560 recommended it in the form of powdered tobacco leaves to the French Queen Catherine de Medice to combat her migraine headaches, and introduced the term Nicotiana tobaccum. Tobacco consumption greatly rose after the I World War, and after the II World War it became very common, especially among man. In the first half of the 20th century the sale of tobacco products rose by 61%, and cigarettes dominated the market of tobacco products. At the beginning of the 20th century cigarettes constituted only 2% of the total sale of tobacco products, while in the middle of the 20th century--more than 80%. Although the first epidemiological papers indicating that "smoking is connected with the shortening of life span" were published in the first half of the 20th century, not until 1950 did Hill and Doll in Great Britain, and Wynder and Graham in USA in 1951 show a statistically significant correlation between cigarettes smoking and lung cancer occurrence. Many controversies according the use of tobacco accompanied it from the beginning of its presence in Europe. The conflicting opinions according to its influence to health coexisted in the 16th to 19th centuries. In this period, especially in the 19th century dominated moral and religious arguments against tobacco. In the 20th century however, and particularly in its second part, development in medical research was enhanced by civil voluntary actions against advertisement and passive smoking. This lead to the significant limitation of tobacco expansion in Europe, USA and Canada in the end of the 20th century. PMID- 17288237 TI - [Influence of tobacco smoking to development of the fetus, newborn and child--a review]. AB - Maternal smoking during pregnancy is associated with not only low birth weight and intrauterine fetal growth retardation or sudden infant death syndrome but also causes complications in postnatal growth and development. The aim of the study was to estimate the effect of tobacco smoking during pregnancy on development of the fetus, newborn and child. We conclude that active and passive smoking during pregnancy is a risk factor for the child. PMID- 17288238 TI - [Is COPD an autoimmune disease caused by smoking?]. AB - Cigarette smoking is the main trigger for the development of chronic obstructive pulmonary disease (COPD). For years the inflammatory reaction in COPD was focused on neutrophils, macrophages and protease-antiprotease balance. The concept of inflammation has been changed since the findings in the bronchoalveolar lavage (BAL) of smokers and COPD patients. It is now evident that the inflammatory reaction composed of neutrophils and macrophages represents the innate immunity reaction. This reaction will proceed over time to damage the lung, producing peptides and modified proteins from matrix destruction, cell necrosis and cell apoptosis. These products have the potential to act as antigen determinants. Dendritic cells which are abundantly present in smokers' lungs are important link between innate and adaptive immunity involving T-cells. These cells mature and migrate to draining lymphatic organs, where they could present antigens to CD-4+ and CD-8+. T-cells that induce their activation and differentiation. As a result T-cells are important component of the chronic inflammation in smokers and in COPD patients. So one of the possible conclusions could be that COPD is a disease produced, at least in part, by self-antigens from the lung secondary to smoking. PMID- 17288239 TI - [Selected respiratory, digestive and urinary system diseases as causes of hospital treatment in the lower Silesia region in aspect smoking-related diseases]. AB - Extensive smoking is impairing function of respiratory, digestive and urinary system. MATERIALS AND METHODS: Analysis was made using data describing hospitalizations in years 2003-2005 caused by respiratory, digestive and urinary system diseases, especially malignant neoplasmas. In analyzed period the count of Lower Silesia region citizens treated in hospitals because of respiratory, digestive and urinary system diseases connected with smoking has dropped. Outside the positive trend stay malignant neoplasms of pancreas, renal pelvis and ureter, lip, oral cavity and pharynx, and bronchiectases. Positive changes in hospitalization because of respiratory, digestive and urinary system diseases could to some extent be assigned as a success of health promotion activities, including anti-smoking actions. PMID- 17288240 TI - [Analysis of changes in most common circulatory system diseases related hospitalizations in the Lower Silesia region in aspect smoking-related diseases]. AB - Cigarette smoking is a risk factor of circulatory system diseases and causes many hospital admissions. Existing data describing hospitalizations because of cardiovascular system diseases in years 2003-2005 were analyzed using statistical methods. In the analyzed years the count of hospitalizations caused by angina pectoris, heart failure, hypertension, atherosclerosis and strokes has dropped, minor changes were visible in frequency of hospital admissions because of acute myocardial infarction and the count of cerebral infarction cases slightly increased. ln the analyzed years in the Lower Silesia region there was visible slight improvement in the area of most main circulatory system diseases. Their hospital treatment is in much extent concentrated in bigger hospitals, because it needs specialized stuff and equipment. PMID- 17288241 TI - [The role of tobacco smoking in etiology of multiple sclerosis--review study]. AB - This article is focusing on the etiology of the multiple sclerosis (MS). MS is the disease of autoimmune origin, concerning mainly young people with its complicated nature. The course of the degenerative and inflammatory process is variable and unexpected, from featureless to the vast and rapidly progressing nature, leading to the considerable disability. The etiological factors are not still well known. We can distinguish different agents: genetic, immunological and environmental, among them tobacco smoking also. Authors survey the etiopathological basis of the disease. PMID- 17288242 TI - [Drug abuse as a menace--anthropological and ethical perspectives]. AB - Threats of drug habit have the multidirectional character. We see, they are connected with the threats of health and with the different social pathologies also, connection with crime closely as well as destructive influence on social reports. The object of article is few-known problems of threats seen in moral perspective. Authors' sentence drug habit acts in man's spiritual interior the largest ravages. Drug dependence leads to disorders perceptions in perspective of reality, lack of ability of sight world different men as well as not understanding only me. From one side the drug addict is a somatic ill (dependence), and from second side, he loses own subjectivity as human person. The basis of contained considerations in article--beside analysis of literature of--subject--were observations of persons dependent from the drugs. Seems, that in prophylaxis of drug habit, as and other dependences, legitimate is the position of larger pressure on aiming to limitation of drug experiments working, in this creating the attitude "I do not try first once". This type prophylaxis can in considerable degree reduce present drug threats. PMID- 17288243 TI - [Beldowski's "the love of fatherland"--patriotism and sale of paper for cigarette wraps]. AB - The tobacco industry has exploited many sophisticated marketing practices. In 1914 in Krakow producer of filters and paper for cigarette wraps published a book devoted to Polish nation history, which was dispensed free among peasants and workers. Advertisements created an association between choosing products from NORIS company and patriotism. PMID- 17288244 TI - [Common errors in analysis of the relationship between variables]. AB - One of the key research problems is the analysis of relationships between variables. Mathematical modeling is commonly used technique in quantification of these associations. This paper describes errors most frequently occurring in simple and complex models constructions such as assumption violation, influence of outliers, data clustering, influence of confounding variables, limited scope of model application. Mentioned problems were illustrated with appropriate examples. PMID- 17288245 TI - [Nanobiotechnology and nanomedicine]. AB - Nanobiotechnology is a new direction in the technological science, which plays a key role in creation of nanodevices for analysis of living systems on a molecular level. Nanomedicine is the application of nanotechnologies in medicine for maintenance and improvement of human life using the knowledge on human organism at a molecular level. Application of nanoparticles and nanomaterials for the diagnostic and therapeutic purposes is now significantly extended in nanomedicine. Use of nanotechnological approaches and nanomaterials opens new prospects for creation of drugs and systems for their directed transport. Implementation of optico-biosensoric, atomic-force, nanowire and nanoporous approaches into genomics and proteomics will significantly enhance the sensitivity and accuracy of diagnostics and will shorten the time of diagnostic procedures that will undoubtedly improve the efficiency of medical treatment. The review highlights data on application of nanobiotechnologies in the field of diagnostics and creation of new drugs. PMID- 17288246 TI - [Immunotoxicity of metals and protective function of pineal factors]. AB - Analysis of the literature data shows that different metals has immunotoxical properties. Biological active compounds of the pineal gland and especially its main hormone, melatonin decreased of toxic shifts through normalization of immune state. PMID- 17288247 TI - [Correction of mitochondrial respiration processes in rats with different resistance to hypoxia under stress by modulators of ATP-sensitive potassium channels]. AB - The effects of the activator of ATP-sensitive potassium channels (K(ATP)) pinacidil (0.06 mg/kg) and the blocker of these channels glibenclamide (1 mg/kg) were investigated using liver and heart mitochondria isolated from rats exhibiting high (HR) or low-resistance (LR) to hypoxia. The animals were subjected to emotional stress. Stress caused activation of mitochondrial succinate oxidation, the decrease of efficiency of alpha-ketoglutarate oxidation and intensification of lipid peroxidation (LPO). These changes were more pronounced in the LR-animals. Administration of pinacidil protected mitochondria under conditions of stress, of whereas glibenclamide abolished these changes. PMID- 17288248 TI - [The activity of 11beta-hydroxysteroid dehydrogenase of rat kidney and liver at inherited stress-induced arterial hypertension]. AB - 11beta-hydroxysteroid dehydrogenase (11beta-HSD) is the key enzyme of glucocorticoid metabolism, which catalyzes interconversion of corticosterone and 11-dehydrocorticosterone in rat. The activity of 11beta-HSD in kidneys of rats with inherited stress-induced arterial hypertension (ISIAH) was significantly (p < 0.05) higher than that in WAG rats. The opposite was observed in the activity of liver 11beta-HSD. Under stress condition no changes in the kidney 11beta-HSD activity of both strains were observed, but the liver 11beta-HSD activity in ISIAH rats was significantly (p < 0.05) higher as compared to basal level and stressed WAG rats. It is possible that the features of the 11beta-HSD activity in ISIAH rats may reflect the hypertensive status of ISIAH rats. PMID- 17288249 TI - [Antioxidant enzymes in skin experimental burn trauma]. AB - The effect of experimental burn trauma (20%) on myeloperoxidase (MPO) and antioxidant enzymes (catalase, glutathione peroxidase (GPO), glutathione-S transferase (GST)) was studied in unburned skin, epidermis (20 mm from the burned area) and the wound tissue of rats. The most common features were the increase of MPO on the 1st day and a delayed increase of GPO and GST after the 4th day. The additional operations (necrectomy) and lipopolysaccharide administration induced marked inflammatory reaction in skin and epidermis (evaluated by the increase in MPO and GPO/GST activities). PMID- 17288250 TI - [The role of small molecules in regulation of activity of cytoplasmatic dehydrogenases]. AB - The influence of silistrong on the activity of erythrocyte cytoplasmatic dehydrogenases and also purified glyceraldehyde-3-phosphate dehydrogenase (GAPH) was studied. Silistrong and its biologically active components (ethanol and silimarine) were found to activate GAPDH, lactate dehydrogenase (LDH), alpha glycerophosphate dehydrogenase (GPDH) both in lysates of erythrocytes and in isolated GAPDH. The compounds studied are able to protect these enzymes and also to restore their activity of enzymes modified by hydrogen peroxide. Maximal activity is a characteristic of silistrong. PMID- 17288251 TI - [Interaction investigation of trypsin inhibitor from sea anemone Radianthus macrodactylus with proteases]. AB - The interaction of inhibitor VJ (InhVJ), isolated from sea anemone R. macrodactylus, with different proteases was investigated. The following enzymes were tested: serine proteases (trypsin, alpha-chymotrypsin, plasmin, thrombin, kallikrein), cysteine protease (papain) and aspartic protease (pepsin). Inhibitor VJ interacted only with trypsin and 6-chymotrypsin. Kinetic and thermodynamics parameters of intermolecular complexes formation were determined: KD = 7,38 x 10( 8) M and 9,93 x 10(-7) M for pairs InhVJ/trypsin and InhVJ/alpha-chymotrypsin, respectively. PMID- 17288252 TI - [The estimation of the antioxidant activity of lacrimal fluid]. AB - A new approach for evaluation of the antioxidant activity of lacrimal fluid (LF) has been proposed. It is based on the method of the analysis of the antioxidant activity of blood and superoxide dismutase activity (Sirota T.V., 1999). In the present work, the method has been first used for examining the antioxidant properties of LF, which is estimated by the ability of LF to inhibit or activate the rate of adrenaline autooxidation in an alkaline medium. The method does not require expensive reagents and equipment; it is simple, accessible, and highly informative. LF of practically healthy people possesses a marked antioxidant activity. In people with symptoms of acute respiratory virus infections, complete loss of the antioxidant activity of LF and the appearance of prooxidant activity were observed. In people taking polyvitamins in prophylactic doses, a significant increase in the antioxidant activity of LF was observed. This method may be applicable in ophthalmology for the diagnosis, control of treatment efficiency, and prognosis of eye diseases. PMID- 17288253 TI - [Study of gene expression of cytokines and apoptotic factors in blood and tissues from patients with surgery infection by the method of real-time polymerase chain reaction]. AB - The expression of cytokines and markers of apoptosis was studied in the whole blood of 10 volunteers by means of reverse transcription method combined with real-time PCR. These factors were also measured in the whole blood, in inflammation nodus tissues and in amputation level nodal tissues taken from 17 patients with local surgical infection. No expression of examined factors in whole blood of volunteers has been observed. However, genes of cytokines and apoptotic markers were expressed in different levels in lymphocytes of whole blood for the case of patients with local surgery infection. This expression was lower in tissues from amputation level and was almost absent in tissues from inflammation nodus, except of the gene, encoding caspase-8. These results suggest that number of pro- and antiinflammating cytokines and apoptotic factors are expressed in peripheral blood and tissue lymphocytes at the formation of System Inflammation Response Syndrom. PMID- 17288254 TI - [Changes of some energy exchange parameters in the rat heart under insulin hypoglycemia]. AB - Hypoglycemic coma induced by administration of a large dose of insulin, was accompanied by the increased rates of glycolysis, glycogenolysis, activity of lactate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, and increased concentration of glycogen. Under these conditions triacylglycerol content decreased administration of the large dose of insulin to rats with alloxan diabetes increased not only rates of glycolysis, glycogenolysis and lactate dehydrogenase activity and also activities of aspartate transaminase and glutamate dehydrogenase. Data obtained suggest the increased utilization of amino acids for energy supply of myocardium under conditions of hypoglycemia induced by insulin adminisration to diabetic animals. PMID- 17288255 TI - [Stimulating effect of recombinant cytokine LIF on the mouse blastocysts during implantation]. AB - We studied the effect of recombinant cytokine LIF (Leukemia inhibitory factor) on the isolated mouse embryos at the stages of middle and late blastocyst. We showed that this agent is necessary at the formation stage of normal trophoblast after the leaving of blastocysts from z. pellucida in vitro. This cytokine (10 ng/ml) results in the intensification of adhesion and proliferative activity of trophoblast cells. It is important for intercellular interactions with endometrium and for invasion of embryos into the uterus. The recombinant LIF has not remarkable influence upon cells of intracellular mass. PMID- 17288256 TI - [Abdominal sepsis: intensive care strategy]. AB - Sepsis is one of the most urgent problems of modern surgery as a steady tendency for the number of patients and mortality rates to increase. Sepsis is the syndrome of a systemic inflammatory response to the invasion of microorganisms. Abdominal sepsis (AS) is inherently a systemic inflammatory response to a focal of infection in the abdomen or retroperitoneal space. Implementation of an individual program for intensive care and anesthetic support is also the same important component of the program for AS treatment as surgery. Intensive care for AS is based on the objective evaluation of the patients' condition, which makes it possible not only to determine the severity of the disease and the degree of organ dysfunction, but also to choose the most adequate intensive care program in terms of a specific clinical situation. The reasonable use of currently available intensive care means and methods substantially reduce mortality rates in patients with AS. PMID- 17288257 TI - [Nutritive support in sepsis: are arguments in favor of a special protocol?]. PMID- 17288259 TI - [Hemodynamics in patients with septic shock and acute lung lesion]. PMID- 17288258 TI - [Clinical pathogenetic types of blood-peritoneal barrier damage in abdominal sepsis]. AB - Many authors point to the peritoneum-blood barrier damage factor in the pathogenesis of abdominal sepsis and peritonitis. The study was undertaken to define the types of blood-peritoneal barrier damage, by providing evidence for a differential approach to intensive care. For this, immunochemical permeability markers and the clinical and laboratory criteria for sepsis were studied in 106 patients. The patients with generalized peritonitis from the sepsis group showed a compensated type of barrier damage. Those with septic shock exhibited its decompensated type. The described types may serve as a criterion for the differential correction of intensive care in abdominal sepsis. PMID- 17288260 TI - [Development of multiple organ dysfunction in sepsis]. AB - The authors studied bioelectrical millivolt-range potentials (omega potential), followed up the health status by the SAPS II and APACHE III scales and organ dysfunction by the MODS scale in patients with sepsis verified by the classification described by R. C. Bone. It was established that in patients with sepsis from the systemic inflammatory response syndrome (SIRS) to the multiple organ dysfunction syndrome (MODS), three main functional groups could be identified with their characteristic clinical course, the level of a lesion, and estimated mortality. In septic patients, the severest condition was noted in a decompensated state when septic shock developed, which was equal to 83 (79.3/ 83) scores by the SAPS II scale. In the patients whose condition was defined as sepsis and severe sepsis in the presence of a subcompensated state, the severity was equal to 55 (51/56.3) scores by the SAPS II scale. The mildest severity (51 (46.8/53.4) scores characterized the development of SIRS or sepsis in the presence of a compensated state. PMID- 17288261 TI - [Inflammatory markers in critically ill children during nutritive therapy]. PMID- 17288262 TI - [Replacement therapy for hepatic failure syndrome]. AB - The results of treatment were studied in 33 patients with hepatic failure syndrome. The patients received MARS therapy or hemodiafiltration as part of intensive care. Albumin dialysis (MARS) may replace hepatic detoxifying function and it is highly effective in diminishing cytolysis in patients with hepatic failure syndrome. Hepatic encephalopathy rapidly regressed with MARS therapy, except for patients with irreversible cerebral changes. The major effect of albumin dialysis is a prompt reducing cytolosis of hepatocytes and liver function stabilization. The most likely mechanisms of action of MARS are the elimination of hydrophobic toxins and the deligandization of albumin molecules, suggesting that MARS is effective in correcting osmotic and colloid ostomic pressures, acid base balance, microcirculation, and hemodynamics, resulting in a decrease in the concentration of proinflammatory cytokines. PMID- 17288263 TI - [Pulmonary extravascular water in patients with acute respiratory failure]. AB - The purpose of the investigation was to study pulmonary extravascular water levels and pulmonary vascular permeability (PVP) in the pathogenesis of acute respiratory failure (ARF)/acute respiratory distress syndrome (ARDS). Twenty-nine patients with ARF/ARDS and 10 healthy volunteers were examined. Central hemodynamics and oxygen transport were explored, by using a Swan-Ganz catheter. Intrathoracic volemic parameters were studied by the transpulmonary thermodilution technique. PVP was assessed by the pulmonary 67Ga-labelled transferrin leakage index. Plasma colloid osmotic pressure (COP) was measured on an osmometer. In most patients with ARF/ARDS, the pulmonary extravascular water index (PEVWI) was found to be higher (mean 16.9 +/- 1.5 ml/kg). At the same time its value was not greater than 10 ml/kg in 7 (24%) of 29 patients. There were no correlations between PEVWI and PaO2/FiO2 and between pulmonary extravascular water and AaDO2. The PVP index (PVPI) measured by transpulmonary thermodilution was 3.2 +/- 0.2, it being normal in 13 (45%) out of 29 patients. The pulmonary 67Ga-transferrin leakage index was higher in all the patients than in healthy individuals (23.2 +/- 2.9 x 10(-3) vs 5.7 +/- 9.9 x 10(-3)) and correlated with PaO2/FiO2 (r = 0.71; p = 0.01). In patients with ARF/ARDS, COP was lower (19.9 +/ 0.7 mm Hg). There were correlations between COP and PEVWI (r = -0.34; p = 0.01), COP and PVPI (r = -0.40; p = 0.044), COP and PaO2/FiO2 (r = 0.35; p = 0.02). PEVWI correlated with the COP-pulmonary wedge pressure gradient (r = -0.45; p = 0.0024). Hypoxemia correlated with intrapulmonary shunt (Qs/Qt). There was no relationship between Qs/Qt and PEVWI in the group as a whole. According to the ratio of Qs/Qt to PEVWI, the patients were divided into 2 groups. Group 1 comprised 11 patients with the ratio < or = 2; Group 2 included 18 patients with the ratio > or = 2, i.e. with an unproportional shunt enlargement as to the severity of pulmonary edema. A correlation between Qs/Qt and PEVWI was found in both groups: r = 0.82; p = 0.001 with the ratio < or = 2 and r = 0.48; p = 0.04 with the ratio > or = 2. Diverse causes of shunt formation were histologically detected. Thus, pulmonary edema was not identified in 24% of patients with ARF/ARDS. Arterial hypoxemia is associated with the increase in the shunt, but, in a portion of patients, the shunt was caused with atelectasis unassociated with pulmonary edema. Increased pulmonary permeability for transferrin is detectable in ARF/ARDS irrespective the severity of pulmonary edema. The pathogenetic features of lung lesions should be taken into account while choosing a treatment for ARF/ARDS. PMID- 17288264 TI - [Recruiting maneuver used in the treatment of respiratory heart failure in cardiosurgical patients]. AB - The possibility of performing the recruiting artificial ventilation technique with a high plateau and positive end-expiratory pressure was studied in 32 cardiosurgical patients, including those with cardiovascular insufficiency. The lung opening maneuver, by using the artificial ventilation adjustable by pressure and the monitoring peak pressure, PDKV, tidal volume, and dynamic compliance, by accurately determining the points of opening and closure is the method of choice in alveolar recruitment. This method permits a significant improvement of arterial oxygenation and dynamic compliance of the lung in patients with acute respiratory failure. This maneuver using the high airway pressures adversely affects hemodynamics particularly in patients with lowered reserves of the cardiovascular system. In this connection, a careful monitoring of hemodynamic parameters is required for the timely provision of cardiotonic and vasopressor support. PMID- 17288265 TI - [Alveolar mobilization maneuver (recruitment): solved and unsolved problems]. AB - Acute respiratory distress syndrome (ARDS) is a common complication in patients with critical condition. Studies of pathophysiological changes in the lung in this condition give rise to new methods of respiratory therapy, one of which is alveolar mobilization maneuver (recruitment). This procedure considerably improves oxygenation in patients with ARDS, but at the same time, there is a risk of developing various complications (barotraumas, lowered cardiac output). Further studies of the efficiency of this method and development of well-defined clinical guidelines that will be able to answer the most important questions: "who", "when", and "how" the alveolar recruiting maneuver should perform are currently under way. PMID- 17288266 TI - [Combined analgesia in early periods after cardiosurgical operations]. AB - The analgesic efficacy of a combination of two analgesic agents (zaldiar and xefocam) was evaluated in 40 patients in the early period after cardiosurgical operations. In Group 1 including 20 patients, analgesia was made with xefocam, 8 mg, every 12 hours. Group 2 received xefocam, 8 mg, twice daily and zaldiar as 2 tablets every 6 hours within the first 24 hours, then as 1 tablet every 6 hours. The intensity of pain was rated according to the verbal scale. Stimulating spirometry was applied to all the patients after extubation. A volumetric spirometer was used to measure the maximum inspiratory lung capacity. The administration of zaldiar and xefocam provides an effective analgesia that permits avoidance or a considerable reduction in the use of potent opioids in the early period after cardiosurgical operations. Stimulating spirometry may be used to evaluate the efficiency of analgesia when patients begin breathing spontaneously after cardiosurgical operations. PMID- 17288267 TI - [Intraoperative use of Xefocam at laparoscopic cholecystectomy]. AB - Xefocam was used in patients with calculous cholecystitis during laparoscopic cholecystectomy to prolong anesthesia and to reduce an inflammatory process in an area under operation. The agent was injected into the round ligament of the liver in a dose of 16 mg intraoperatively and in a dose of 8 mg postoperatively. The proposed method was applied to 52 patients operated on for acute and chronic calculous cholecystitis. Fifty patients receiving the conventional anesthesia with the narcotic analgesic promedol were examined to evaluate the efficiency of the new procedure of anesthesia; the later being effective in 96.2% of the patients. The findings indicated the high efficiency of the proposed procedure without side effects observing in the use of narcotic analgesics. Furthermore, the nonspecific anti-inflammatory activity of Xefocam promotes a reduction in the number of postoperative local inflammatory complications. PMID- 17288268 TI - [Clinical aspects of analgesia with intravenous paracetamol in the early postoperative period]. AB - This open one-center study included 40 patients operated on the abdomen and chest, who had moderate resting pain in the immediate postoperative hours. Paracetamol was used as a dropwise intravenous 1-g infusion for 10-15 min; the dose of the agent was 4 g. The interval of paracetamol re-infusion was not early than 4 hours. If additional analgesia was required, opioid analgesics (promedol, tramadol) were administered. As a whole, assessment of analgesia within 24 hours showed excellent and good results reported by patients in 85% of cases; and in 71% of the patients the intensity of postoperative pain was less than they had expected before surgery. The use of opioid analgesics was required in 65% of the patients and 25% did not need these agents. The remaining 10% of the patients received a combination of nonsteroidal anti-inflammatory drugs, paracetomol, and opioids. Postoperative analgesia based on the intravenous infusion of paracetamol in a single dose of 1 g (4 g/day) caused a reduction in the intensity and duration of pain. The intravenous formulation of paracetamol should be regarded as one of the essential nonopioid components of multimodality therapy for pain in patients in the early postoperative period. PMID- 17288269 TI - [Prediction of fatal outcome in severe injury]. AB - The paper reflects the results of a study to predict a fatal outcome in severe injury, by evaluating the condition by the APACHE II, SAPS II, MODS, SOFA, and Glasgow coma scale. Particular emphasis is laid on the assessment of the quality of an obtained prediction, by using the currently available tools--the resolving power of a prognostic model (area under the characteristic curve), choice of the prognostive value (division point), and calibration of the model. It was ascertained that the APACHE II and SAPS II scales could not significantly predict a fatal outcome in severe injury. Based on the scores obtained by the SOFA, MODS, and Glasgow coma scales, the authors developed prognostic indices that provide a high significance in predicting the fatal outcome in severe injury both within the first 24 hours and over time. The independent predictor of a fatal outcome (hypernatriemia) in severe injury was identified. PMID- 17288270 TI - [Transcutaneous dilation tracheostomy in the acute period in patients with penetrating craniofacial injury complicated by intracranial hypertension]. AB - Early tracheotomy is well founded in severe brain injury involving the facial skeleton and skull case. Intracranial hypertension interferes with the safe performance of an operation. The authors developed a procedure for safe paracentetic dilatation tracheostomy (PDT) in the acute phase of severe brain injury. The study covered 15 patients with severe brain craniofacial injury. Surgery was made under intravenous anesthesia (with hypnotics, myorelaxants, narcotic analgesics, and cholinolytic agents). PDT was performed by the combined procedure developed by Sigley and Griegse ("Portex and COOK") under endoscopic guidance (Karl Storz 11001 BN1), by displaying the images. The patient is put to bed, without placing a bolster under the shoulders, the bed head end being elevated at an angle of 30 degrees. Bronchoscopic monitoring was made discretely (20-60 sec) under artificial ventilation through a special connector. There were 3-6 sessions of bronchoscopies. Tracheostomy lasted as long as 24 hours in 5 patients, 48 hours in 12 patients; surgery was made in 7 patients on day 3 after injury. Prior to tracheostomy, a horizontalization test was conducted, which revealed an elevation of intracranial pressure (> or = 20 mm Hg). There were no episodes of intracranial hypertension during tracheostomy. PDT can be safely made in patients with intracranial hypertension when they are put to bed, without placing a bolster under the shoulder, the bed head end being elevated at an angle of 30 degrees under discrete bronchoscopic guidance. PMID- 17288271 TI - [A diagnosis and treatment protocol for brain injury]. AB - Brain injury is one of the main causes of death in 20-40-year-old persons. The main causes of fatal outcomes are progressive edema and cerebral ischemia. The strategic task of intensive care in patients with severe brain injury, who are critically ill, is to prevent and treat secondary ischemic brain damages. The major secondary damaging factors include arterial hypotension, hypoxemia, hyper- and hypocapnia, hypoosmolality, and hyperglycemia. This paper presents the advisable treatment protocol for patients with brain injury, which has been developed and used in a neurosurgical intensive care unit of the N. V, Sklifosofsky Research Institute of Emergency Care. The protocol is based on international guidelines and the authors' own studies. It outlines the basic lines of monitoring and intensive care in patients with severe brain injury. PMID- 17288272 TI - [Efficacy of intravenous immunoglobulins in bacterial infections]. PMID- 17288273 TI - [Artificial hypocoagulation during cardiosurgical operations and its monitoring]. PMID- 17288274 TI - [Pitfalls of polypharmacy, particularly in the elderly]. AB - Many patients, especially those aged over 70 years, receive variable types of polypharmacy in western countries. Polytherapy may be naturally in accordance with good clinical practice, or vice versa, it may be unjustified, whether it results from inappropriate prescribing or self-medication. Major causes of polytherapy include the presence of multiple disease states, thereby necessitating multiple drug therapy, particularly in patients with chronic debilitating disorders; increasing demand for health care; therapeutic advances as well as excessive prescribing (which may be related to poor coordination between practitioners). Polypharmacy may result in: increased rates of adverse drug reactions, as a frequent consequence of drug-drug interactions; errors in medication-taking, including poor compliance due to drug-associated untoward effects and medication errors; both direct and indirect additional costs for the health insurance scheme. Preventive measures of adverse drug reactions should include: appropriate clinical trials to improve knowledge of risks of polytherapy in elderly patients and other patients at high risk for developing drug-related side-effects; improved adverse drug reaction reporting to the pharmaco-vigilance systems provision of information about drug side-effects to all health care professionals as well as to patients. PMID- 17288275 TI - [Acute methanol intoxication: physiopathology, prognosis and treatment]. AB - Acute methanol poisoning is mainly the consequence of voluntary or accidental ingestion. The mortality and morbidity rates remain very high despite intensive care therapy. Methanol by itself is poorly toxic. Methanol is transformed in the liver into formaldehyde and thereafter formic acid. Metabolic acidosis is the main biological feature of poisoning. Acidosis is related to formic acid accumulation, and also to a less extent to lactate production. In contrast to rodents, primates are relatively deficient in tetrahydrofolate reductase and therefore formic acid is usually the final metabolite. Formic acid is able to inhibit cytochrome oxidase activity in the mitochondria, leading to histotoxic hypoxia. The most sensitive organs to the effects of formic acid are the brain and the visual pathway, while other organs may also be seriously damaged according to the severity of metabolic acidosis. Hemodialysis remains indicated for the removal of both methanol and formic acid. Fomepizole is a recently approved antidote. It appears safe and effective. Analysis of its cost effectiveness ratio is still ongoing in methanol poisoning. PMID- 17288276 TI - [A clinic and a paraclinic study of Tunisian population of children with autism. About 63 cases]. AB - Autistic disorder is a pervasive developmental disorder which starts before the age of 3. The clinic features of autism are variable; the autonomy degree, the speech quality, the mental retardation associated and specially the existence of an organic disease change its clinic expression. A good knowledge of the basic signs is important to put diagnosis. This work, propose to describe a clinic and a Para clinic profile of Tunisian population of children with autism. The study included 63 children referred to the child psychiatry department between January 1998 and September 2003 and diagnosed with autistic disorder according to DSMIV and ADI-R criteria. The population profile studied is drawn as following : The sex ratio was of 3/1, the average age was of 8 years+/-3 years. Parents were related in 39.3% of cases. On the clinical plan, 51.2% of children with autism studied did not have expressive speech. They presented a mental retardation associated in 60.8% of cases. Epilepsy was presented in 21 children out of 63. This profile links literature study except in 2 points: - The rate of relatives with autism (8.6%) is superior to the rate found in literature(3%). This result can be explained by the high rate of consanguinity in the Tunisian studied population (39.3%). - Importance of associated organic pathologies (mental retardation). PMID- 17288277 TI - [Evaluation of psychological disorders in Tunisian patients with inflammatory bowel disease. A comparative case-control study]. AB - AIM: To evaluate the psychological state in Tunisian patients with inflammatory bowel disease using the general health questionnaire in 12 items. METHODS: A prospective case-control study was performed, including 60 cases of Crohn's disease. 60 cases of ulcerative colitis and 60 healthy control subjects. The total score of the general health questionnaire was calculated on the basis of 0 0-1-1 system. RESULTS: The total score of the general health questionnaire was significantly higher in inflammatory bowel disease patients compared to control group (3.70+3,57 vs 0,16+ 0,52, p<0.0001). In inflammatory bowel disease patients, the total score of the general health questionnaire was significantly higher in Crohn's disease patients compared to ulcerative colitis patients (4,40+3,84 vs 3.01+3.18,p=0.03) and in case of active disease compared to quiescent disease (5,57+3.18 vs 1,64+2,78,p<0.0001). CONCLUSION: Psychological disorders are frequent in Tunisian patients with inflammatory bowel disease, essentially in patients with Crohn's disease or in case of active disease. PMID- 17288278 TI - [Chronic atrial fibrillation in adults: direct current cardioversion or medical cardioversion]. AB - To study cardioversion modalities of atrial fibrillation, we had a look to 100 cases hospitalized in Mongi slim cardiologic department during the period lasting from January 1993 to July 2001. Medical cardioversion (with amiodarone) was performed in 47 patients and electrical cardioversion in 53 patients. Atrial fibrillation was 17 months old. Vavular heart disease was the main etiology (65%). The primary success rate of medical cardioversion (73%) was equivalent to electrical cardioversion (70%). Oldness of atrial fibrillation was the only predictive factor of failure of cardioversion. PMID- 17288279 TI - [Mycobacterial infections in children in Central Tunisia. A study of 31 cases including 7 disseminated BCG-osis]. AB - In order to analyze the current epidemiological pattern of mycobacterial infection in children in Central Tunisia, we studied retrospectively the clinical feature of 31 children with mycobacterial infection enrolled in the pediatrics department of Sousse during eight years period (1994-2001). Twenty three boys and eight girls aged two months to 13 years (mean age: 4 years and 8 months) were investigated. Among them, 24 patients suffered of tuberculosis (TBC) and 7 of disseminated BCG-osis. Pleuropulmonary TBC was observed in 12 patients either isolated (7 cases) or in association with at least another localization (5cases). 17 patients had extrapulmonary TBC with variable localisation. The 7 patients with disseminated BCG-osis had an underlying primary immunodeficiency of the cell mediated immune response. CONCLUSION: The current epidemiology of mycobacterial infections in children in our region indicates a high frequency of severe adverse effects of BCG vaccination occurring in genetically immunodeficient children. PMID- 17288280 TI - [Beating heart coronary revascularisation. Report of 26 cases]. AB - The beating heart coronary artery bypass technique is becoming more popular in many cardiac units throughout the world. This relativity new technique has prompted surgeons and anaesthetists to review and analysed the routine approach to coronary surgery. In this study we reviewed 26 patients operated off pump technique group I (50 %) and the group II (50 %) operated on pump coronary artery bypass. The patients in the group II were more symptomatic with more heart function, than group I. The postoperative cause of the two groups was similar. This retrospective analysis shows that beating heart technique for coronary surgery can be offered to many patients with good out come and on pump technique can be more safety specially in case of poor myocardial function. PMID- 17288281 TI - [Results of laparoscopic treatement of common bile duct lithiasis. Report of 30 cases]. AB - AIM: The aim of this retrospective study was to report the results of the laparoscopic management of common bile duct stones in an unicentric series of 30 patients. METHODS: From January 2001 to April 2004. 30 patients: 23 women, 7 men (mean age: 54 years). underwent a common bile duct exploration for lithiasis through a laparoscopic approach. The patients were hospitalized for angiocholitis (n = 12), cholecystitis (n= 4), jaundice (n = 4), pancreatitis (n = 3), abnormality of hepatic tests (n = 7). All the patients underwent an intra operative cholangiography. Removal of the stones was tried in 30 cases through a choledochotomy. never through the cystic duct, using Dormia and Fogarty catheters. External biliary drainage with T tube (kehr) and postoperative cholangiography was done systematically. RESULTS: In 21 patients (70 %), removal of the stones was laparoscopically successful. The average diameter of the common bile duct was 10.5 mm (range 6-20 mm). The median number of stones was 5 (E: 1 12). The median operation time was 180mn (range 150-300mn). In 9 patients, a conversion into laparotomy was necessary for several reasons. In 2 patients with residual common bile duct, the stones were treated successfully by endoscopic sphincterotomy. There was no mortality and the morbidity rate was 10 %. The mean postoperative hospital stay was 14.7 days (range 7-18days) and 13.3 days in case of successful laparoscopic management. CONCLUSION: In 70 % of the patients, the treatment of the common bile-duct lithiasis could be achieved laparoscopically, but conventional approach and endoscopic sphincterotomy are still useful in case of failure of the laparoscopic management. PMID- 17288282 TI - [Association of benign prostatic hyperplasia and hernia inguinale. A report of 55 cas]. AB - THE AIM: of this study is to evaluate the results of combined surgery of prostatic disease and inguinal hernia repair. METHODS: We report a retrospective study of 55 patients operated in the same operating time for benign prostatic hyperplasia and hernia inguinale, and present our criteria for patient selection, operative technique, and postoperative results. RESULTS: The mean age of our patient was 69 years with a range of 56 to 85 years. Open suprapubic prostatectomy was done in 53% of cases, transurethral prostatic resection in 47% of cases and prothetic hernioplasty in 60% of cases. The incidence of postoperative wound infection and recurrent hernia was 5,4 % and 6% respectively, witch compares favorably to results of herniorraphy and prostatectomy performed separately. Simultaneous repair of inguinal hernias and surgery of prostatic disease is effective and technically feasible. PMID- 17288283 TI - [Bibliometric profile of Tunisians medicals publications indexed in Medline from 2000 to 2003 party 1: productivity and cartography]. AB - OBJECTIVE: The objective of this work is to quantify the Tunisian productivity in medical publications, and to determine its national cartography. METHODS: It turns about a descriptive bibliometric study of the Tunisian medical researches through the whole of the papers indexed in the Medline database, and this during the period of four years, between 2 000 and 2 003. We retained only the articles which satisfied the two following conditions: on the one hand the address is a tunisian health structure and on the other hand, the first and/ or the last author is a tunisian doctor. RESULTS: Among the 2057 medical articles found during of the request of Medline's database, I 248 papers were eligible to the study. The indicators of the national productivity in medical publications were 27.3 articles / 100 teacher / year, de 3,2 articles / 100 W(X) habitants / year et de 10,6 articles / billion dinars / year. In addition, 97.33% of the medical tunisian publications have been produced by the hospitalo-university structures. CONCLUSION: It results of this study that the tunisian medical research is characterized by a low productivity and an important hospitalo centrism. Its development requires on the one hand more formation of doctors in research's methodology and in medical writing, and the other hand a structured activity medical documentary wakefulness and bibliometric analysis. PMID- 17288284 TI - [Nevus lipomatosus cutaneous superficialis: a clinico-pathological study of 13 cases]. AB - Nevus lipomatosus cutaneous superficialis (NLCS) is a rare hamartomatous skin lesion histologically characterised by the presence of mature fat tissue within the dermis. Clinically, two types of NLCS can be distinguished: a multiple type of Hoffmann-Zurhelle and a solitary type. We report a retrospective study of 13 cases of NLCS seen in the Anatomopathological department of La Rabta hospital of Tunis during a period of 12 years (1992-2004). Two clinical forms were distinguished: the solitary form (11 cases) consisting of a unique papulo-nodular lesion and the multiple form (2 cases). Histologically, the tumor consisted in all cases on mature fat tissue. PMID- 17288285 TI - [Study of dyslexia within school kids that suffer from epilepsia]. AB - Dyslexia is a reading problem disorder. It can be a direct result of epilepsia for some kids. The researchers have done the study on 30 school kids that suffer from epilepsia. All the children had Audiometry which was normal in all cases. The orthophonic exam has done in all cases, founding a prononciation and speaker disorder also there is disorder at the psychometric test The purpose of the study research is to define the different profiles of dyslexia on the epileptics, then to check the importance of collaboration between Otorhinolaryngologists, Neurologists and Orthophonists to take care of the epileptic kids having dyslexia. PMID- 17288287 TI - [Image in clinical practice]. PMID- 17288286 TI - [Toxoplasmic infection in pregnancy. Report of 12 cases]. AB - The toxoplasmosis is a protozoal infection which is capable to induce an infection. Often fatal in the newborn babies infected by transplacental way, thus, the discovery of a toxoplasmic seroconversion during the follow up of the pregnant women had posed to the obstetrician some problems in the manegement. We reported 12 observations of toxoplasmic seroconversion during pregnancy with literature review. PMID- 17288288 TI - Vertebral tuberculosis revealed by thoracic manifestations. A study of five cases. AB - BACKGROUND: Spine is the most frequent location of bone tuberculosis, which can seldom be revealed by thoracic manifestations. METHODS: In a seven-years retrospective study, we reported radioclinical manifestations revealing Pott's disease, methods of diagnosis and the treatment outcome. RESULTS: Five non immunocompromised female patients were hospitalized between 1997 and 2003 in Clinical Department of Pulmonary Diseases in Abderrahmane Mami Hospital Ariana Tunisia, for thoracic manifestations that led to the diagnosis of Pott's disease, which represents 4.2% of extrapulmonary tuberculosis and 1.3% of all cases of tuberculosis cared for in the same period. The median age was 48.6 years. The disease was revealed by a paramediastinal radiographic shadow infiltrating the contiguous left lung in one case, abscesses of chest wall in two cases. Another patient was hospitalized for a tuberculous empyema. The last case had a diffuse miliary shadow in both lungs. All patients complained from thoracic or respiratory problems and constitutional symptoms, that evolved for an average of 5.6 months. Computed tomography (CT) and magnetic resonance imaging (MRI) of the spine identified monolevel spondylitis in two cases and multilevel disease in three cases. Diagnosis of tuberculous infection was confirmed in only one case by CT-guided biopsy of a perivertebral abscess, it was retained in three cases by bacteriological and or histopathological exams obtained from extra-vertebral lesions, and presumed in the fifth on a favorable treatment outcome. All patients had at least one extra-vertebral location of tuberculosis. Four patients were treated successfully with antituberculosis chemotherapy, prescribed for 18 to 22 months. Relapse occurred only in one patient, who received 12 months of treatment. CONCLUSION: Pott's disease can be observed in non immunocompromised patients. In the Lung Diseases Department, it is often revealed by thoracic manifestations and associated to pulmonary lesions, which makes the formal diagnosis easy. Here, vertebral tuberculosis does not have anatomical specificities; nevertheless, the multilevel forms are relatively frequent. It constitutes an index of bacillus dissemination, requiring the search for other extra-vertebral locations. PMID- 17288289 TI - [Melkersson-Rosenthal syndrome. Report of five cases and review of the literature]. AB - The goal of this work is to report five cases of Melkersson-Rosenthal syndrom with a literature review. It is a rare entity and is characterized in its complete presentation, by the association of reccurent orofacial swelling, peripheral facial palsy and plicated tongue. Incomplete forms are more frequent and more difficult to establish its diagnosis. This latter is based on major and minor clinical and histological critieria sorted in three levels. There is four forms of MRS. The pathogenesis of this syndrome is still unknown; treatment remains random. It is based on topical or systemic steroids with or without cheiloplastic procedure. We must think of MRS in presence of any recurrent peripheral facial palsy and/or chronic facial swelling. PMID- 17288290 TI - [Gliomatosis cerebri]. AB - The Gliomatosis Cerebri (GC) is an infiltrating and rare primitive tumour of the brain. It is characterized by diffuse neoplastic proliferation of glial cells involving of at least two lobes of the brain, without a distinct tumor mass and with the preservation of the anatomical and neuronal architecture. According to the WHO classification, GC is categorized as a high-grade neuroepithelial tumor of uncertain origin (GradelV). Now the diagnosis is facilitated via stereotactic biopsies of the representative lesion identified in magnetic resonance. Our objective is to present 4 new cases, and recall the clinical and radiological features and the prognosis. PMID- 17288291 TI - [Pseudotumor cerebri with all-trans retinoic acid. A case report]. AB - The diagnosis of pseudotumor cerebri (PC) is based on the triad of: (1) papilledema, (2) elevated intracranial pressure with a normal cerebrospinal constituency and (3) normal central nervous system imaging studies. It is an uncommon complication of all-trans-retinoic acid (ATRA) therapy in children treated for acute promyelocytic leukaemia (APL). Its occurrence is rare among adult patients with APL and treated with ATRA . We report a case of an adult with APL who developed PC during induction therapy with ATRA-PC was managed with repeated lumbar punctures and corticotherapy. PMID- 17288292 TI - [Renal adenocarcinoma in horseshoe kidney, report of a case]. AB - Tumors arising within horseshoe kidney are uncommon and may be difficult to identify. The incidence of tumor within horseshoe kidney is higher than in the normal one. Adenocarcinoma is the most common tumor. The nephrectomy is considered as partial and the patients need a strict follow up. Horseshoe kidneys show a lot of variety with regard to supporting arteries and veins. Therefore, a selective study of the renal vessels should be performed preoperatively. Abdominal angiography should be done to study this vasculature. PMID- 17288293 TI - [Rhinoscleroma]. AB - PURPOSE OF STUDY: Rhinoscleroma is a chronic infectious granuloma due to Klebsiella rhinoscleromatis. The aim of the study is to precise clinical. paraclinical and therapeutic aspects of rhinosclerome. MATERIAL AND METHODS: We propose a study about 3 cases of rhinosclerome collected in a period of 15 years. Nasal endoscopy was realised in all cases with a bacteriological sampling and a histological examination of nasal lesions. We realised nasosinusien scanner in all cases. RESULTS: All patients have a progressive and bilateral nasal obstruction. Cruts rhinitis was observed in 2 cases. Laryngal scleroma was observed in one case. The diagnosis was confirmed by histological examination and bacteriological sampling. All patients were treated with fluoroquinolones. The evolution was satisfactory in 2 cases. CONCLUSION: Sclerome is a cosmopolitan disease which requires early diagnosis and treatment. PMID- 17288294 TI - [Endometriosis with urinary manifestation. A case report]. AB - Endometriosis is an ectopic implantation of endometrial tissue. Authors report a case of a 33 year-old infertile women who presented a deep pelvic endometriosis infiltrating the right ureter with left ovarian endometrioma suspected by the ultrasonography and confirmed with MRI. The patient was treated with Gn-RH analogues with relief of symptoms and normalisation of the upper urinary tract. PMID- 17288295 TI - [A child elbow calcific bursitis: no hasty surgical option. A case report]. AB - We report the elbow calcific bursitis case of an 11 years old child. The imaging let us notice a lateral peri-articular calcifying and we planned a surgical biopsy. But the tumour spontaneous resolutive development in the clinical aspect and its ray disappearance led to a therapeutic abstention. The set of clinical elements, the imaging and the development let us come to a calcific bursitis diagnosis, exception for a child. These calcifyings are located in the sinew bursa. virtual cavities in a normal state. They are related to a sinew chronic antagonism with an anatomic bony ground and they generally develop in a spontaneous resolution with a macrophagic resorption. However their rare occurrence for a child must lead us to be extremely cautious in the diagnostic of child bony tumours in general and extra-bony calcifyings in particular: the rule must be the imaging result and the biopsy. PMID- 17288296 TI - The Johnston--Kennedy era. A quarter of a century of change. PMID- 17288297 TI - Are we failing those with 'The Falling Sickness'? Time to modernise the approach to epilepsy care. PMID- 17288298 TI - Proximate determinants of fertility and reproductive health. PMID- 17288299 TI - Chronic Myeloid Leukaemia in The 21st Century. PMID- 17288300 TI - Percutaneous coronary intervention in the elderly. AB - OBJECTIVE: To determine the clinical risks and procedural outcomes for elderly patients undergoing percutaneous coronary intervention (PCI). METHOD: A retrospective case-load analysis was performed of all patients over the age of 80 years, undergoing PCI, over a two-year period, in a tertiary referral hospital. Patient demographics, procedural details and in-hospital complications were obtained by reviewing patient notes. Twelve-month outcomes were obtained from telephone follow-up to the general practitioners and all surviving patients. RESULTS: There were 55 procedures. Procedural risk was high, with a median TIMI risk score of four (IQR 3-6) and a median additive EuroSCORE of nine (IQR 8-10). There was a 95% angiographic success rate. There were no in-hospital complications. Median Canadian Cardiovascular Society angina class fell from four (IQR 3-4) to one (IQR 0-1). At one year there were twelve deaths (10 cardiovascular), eight of these occurred in patients who had incomplete revascularisation. CONCLUSION: PCI can be performed in an elderly, high-risk population with a low in-hospital mortality and marked symptomatic benefit. However, there is a significant 1-year mortality, particularly in patients who are only suitable for partial revascularisation. PMID- 17288301 TI - The use of contrast-enhanced ultrasound in the characterisation of focal liver lesions. AB - PURPOSE: To determine the potential application of contrast-enhanced ultrasound in the characterisation of focal liver lesions encountered in radiological practice at a district general hospital. MATERIALS & METHODS: Retrospective analysis of 68 sequential patients undergoing contrast-enhanced ultrasound (CEUS) of liver. All patients were referred for CEUS following identification of 1 or more focal liver lesions on conventional ultrasound or CT imaging. After baseline US examination (Acuson), a bolus of 1.0-2.4 ml of SonoVue (Bracco, UK) was administered intravenously. CEUS images were obtained during arterial, portal venous and delayed phases. Patients were followed up for a mean period of 6 months. The CEUS diagnosis was compared to that indicated by other imaging modalities, histopathology, and clinical follow up. RESULTS: CEUS correctly identified malignant liver lesions in 19 patients, with the final diagnosis confirmed by histopathology in 5 cases and clinico-radiological follow up in 14 cases. 47 patients were correctly identified with benign liver lesions on CEUS imaging, with all these cases confirmed on clinico-radiological follow up. In the detection of malignancy, the sensitivity was 95.0% and the specificity was 97.9%. CONCLUSIONS: In our experience to date, contrast-enhanced ultrasound imaging is highly accurate in characterising malignant and benign focal liver lesions. It therefore has significant potential for utilisation in most general radiology departments. PMID- 17288302 TI - Medicine then and now. Presidential address to The Ulster Medical Society, 12th October 2006. PMID- 17288303 TI - The history of gastric surgery: the contribution of the Belfast School. PMID- 17288304 TI - Bowel perforation caused by swallowed chicken bones--a case series. PMID- 17288305 TI - Acute transverse myelitis following typhoid vaccination. PMID- 17288306 TI - Profuse per rectal bleeding due to erosion of the inferior epigastric artery following a catheter tube caecostomy. PMID- 17288308 TI - The new chief medical officer for Northern Ireland. Interview by Claire T Lundy. PMID- 17288307 TI - Peritoneal encapsulation: presenting as small bowel obstruction in an elderly woman. PMID- 17288310 TI - Local council shuns private sector and builds its own nursing homes. PMID- 17288311 TI - Know your limits or face increased threat of compensation claims. PMID- 17288312 TI - Held to account. tt. AB - Representatives of two nursing organisations offer a summary of nurses' legal position in relation to unsafe staffing levels. PMID- 17288313 TI - Is this the end of the branch system? AB - Changes in nurse education will need to take place if the more flexible workforce envisaged in Modernising Nursing Careers is to become reality. PMID- 17288314 TI - There is nothing soft about spirituality. PMID- 17288315 TI - Freedom to be unhealthy. PMID- 17288316 TI - Supporting nursing students with dyslexia in clinical practice. AB - AIMS: To determine whether pre-registration nursing students with dyslexia experience specific problems in developing clinical competence, identify what strategies they use and how they may be supported in clinical practice. METHOD: Qualitative case study methodology was used. Stage 1 involved semi-structured interviews with seven students, three support and eight teaching staff, postal questionnaires from nine mentors, in addition to a review of policy documentation. Stage 2 involved a two-year study of four students on their branch programme and included semi-structured interviews with seven mentors. FINDINGS: The students' difficulties in clinical practice fell into three categories: dealing with information; performing the role; and administering drugs. Specific supporting measures included: informal and formal support networks; portable information technology equipment; and personal strategies, for example, rehearsing difficult tasks such as the handover report. The students' relationships with their mentors and the type of environment they were working in were key to the successful development of clinical competence. CONCLUSION: Nursing students who have dyslexia have specific learning difficulties in practice. Their response to these difficulties is individual and support needs to be tailored to meet their specific needs. PMID- 17288317 TI - Developing a service for children with iron deficiency anaemia. AB - The IDEAS (Iron Deficiency Early Anaemia Services) project is a programme aimed at detecting and offering a system of care for children with iron deficiency anaemia. It is designed and run by health visitors and nurses in an inner-city area of Bradford. Children with low haemoglobin are referred by the health visitor to the specialist nurse-led clinic. Dietary advice consistent with tradition and culture is given and appropriate referrals made to the GP for iron supplementation, and to the consultant paediatrician or haemoglobinopathy adviser when appropriate. An important development has been the identification of a previously undiagnosed abnormal haemoglobin trait. PMID- 17288318 TI - Promoting sexual health: practical guidance on male condom use. AB - Condoms are the only form of contraception that, when used correctly, can reduce the risk of pregnancy and transmission of sexually transmitted infections. This article outlines strategies for promoting correct male condom use. The availability, variety and history of condoms are explored. Possible reasons for people not wanting to use condoms are examined and advantages of condom use are provided. The author suggests ways in which healthcare workers can promote condom use and improve the experience and efficacy of this contraceptive device. PMID- 17288319 TI - Osteoporosis. PMID- 17288320 TI - Safe in our hands. PMID- 17288321 TI - Highly prized. PMID- 17288322 TI - 10-year clinical evaluation of a self-etching adhesive system. AB - This study evaluated the long-term clinical performance of a self-etching adhesive system, Clearfil Liner Bond 2. Two operators placed a total of 87 restorations among 42 patients. Carious dentin was identified with the help of Caries Detector and was removed using only a low speed round bur. Clearfil Liner Bond 2 was applied following the manufacturer's directions, and the resin composite was then placed. The number of restorations placed by cavity classification were: 8-Class I, 11-Class II, 21-Class III, 2-Class IV and 45 Class V. The restorations were evaluated in 5 categories according to modified USPHS criteria: pulpal response, marginal integrity, marginal discoloration, retention and secondary caries. Assessments were done at baseline, immediately after placement and at 6-months and 1, 5, 7 and 10 years. Recall rates at each assessment period were 83.9% (6-months), 82.8% (1 year), 59.8% (5 years), 77.0% (7 years) and 50.6% (10 years). In terms of assessment categories, there were no recorded sensitivity, retention loss or secondary caries at any of the five recall periods. At the 10-year assessment, 40 out of 44 restorations (90.9%) were rated Bravo for marginal integrity and 39 restorations (88.6%) were rated Bravo for marginal discoloration (Wilcoxon signed-ranks test p < 0.05). This data demonstrates the retention rate and pulpal response of the self-etching adhesive system Clearfil Liner Bond 2 was excellent at 10 years. Most cases showed slight marginal changes during clinical function; however, these changes were not clinically severe by USPHS criteria. These data demonstrate that placement of the Clearfil Liner Bond 2 self-etching adhesive system was demonstrated to be acceptable for the clinical restoration of human teeth following 10 years of clinical function. PMID- 17288324 TI - Effect of various surface treatments on the microleakage and ultrastructure of resin-tooth interface. AB - This study evaluated the effect of collagen removal and sodium ascorbate treatment of acid-etched dentin on the microleakage and ultrastructure of resin tooth interface under moist and dry conditions using an acetone-based 1 bottle adhesive system. Class V cavities were made on the buccal surfaces of 90 premolars scheduled for orthodontic extraction. The cavities were etched with 37% phosphoric acid (DPI tooth conditioning gel/India) for 15 seconds. The teeth were divided into six groups with 15 teeth each. In Group 1, the etched surface was blot dried with a dry cotton pellet, leaving it visibly moist, and Prime & Bond NT (Dentsply Detrey/ Germany) was applied. In Group 2, after acid conditioning, the cavity surface was air dried for five seconds, followed by application of Prime & Bond NT. In Group 3, 3% NaOCl (Hyposol, Prevest Denpro Ltd/India) was applied to the acid-conditioned cavity surface for two minutes. The surface was blot dried before bonding. In Group 4, after NaOCl treatment, the surface was air dried for five seconds, followed by application of the bonding agent. In Group 5, 10% sodium ascorbate (chemically pure) was applied to the NaOCl-treated acid conditioned tooth surface for one minute. The surface was blot dried before bonding. In Group 6, after sodium ascorbate treatment as in Group 5, the cavity surface was air dried for five seconds before bonding. The cavities were restored with the hybrid composite Spectrum TPH (Dentsply Detrey, Konstanz, Germany). The teeth were extracted immediately after restoration, and the specimens were prepared for microleakage testing using 2% methylene blue dye and for scanning electron microscopic evaluation. The results of the dye penetration were analyzed with Kruskal-Wallis non-parametric analysis followed by the Mann-Whitney U test at a significance level of p = 0.05. After acid etching, the conventional acid etched groups and groups with NaOCl treatment demonstrated extensive leakage. Sodium ascorbate treatment of the NaOCl-treated dentin significantly reduced microleakage. No statistically significant difference between moist and dry bonding was observed in all groups. Although resin tag penetration improved in both the NaOCl-treated and NaOCl/ascorbate-treated groups, an absence of gap at the resin dentin interface was observed only for the NaOCl/ascorbate-treated groups. PMID- 17288323 TI - Clinical evaluation of three adhesive systems for the restoration of non-carious cervical lesions. AB - The use of adhesive materials to restore non-carious cervical lesions (NCCL) has become the standard practice. Until recently, the most reliable material for restoring NCCL is glass ionomer cement, but the esthetics can be problematic. This study compared the retention of a self-etching adhesive, Clearfil SE Bond, with Clearfil ST resin composite (SE), with the phosphoric acid-etch single bottle adhesive Single Bond with A110 resin composite (SB) and a resin-modified glass ionomer cement, Fuji II LC, (FJ). Ninety-two restorations in 20 patients (mean age 61 years) were placed. The teeth were restored randomly and manufacturers' instructions were followed. Patients were recalled at 6 months, 1, 2 and 3 years and the restorations were evaluated for marginal staining. The restorations were photographed at baseline and at recall periods. At one year, 80 restorations were available for evaluation; at 2 years, 65 restorations were evaluated and at 3 years, 55 restorations were evaluated. The cumulative retention rates at 1 year, 2 years and 3 years, respectively, were SE: 97%, 93%, 90%; SB: 86%, 77%, 77%; FJ: 100%, 100%, 97%. At 3 years, RM-GIC performed the best, followed by Clearfil SE Bond/Clearfil ST. Single Bond/A110's performance was significantly less than the other 2 materials (p = 0.012). PMID- 17288326 TI - Shear bond strength of two resin cements to human root dentin using three dentin bonding agents. AB - This study compared the bond strength of two resin cements to human root dentin when used with three bonding agents. The materials used were Rely X ARC and Perma Cem, two one-bottle bonding agents (Single Bond, Bond-1) and one self-etching bonding agent (Clearfil SE Bond). The dentin was obtained from single rooted human teeth, and the specimens were treated with either 15% EDTA or 37% phosphoric acid to remove the smear layer, except in groups where the self etching bonding agent was used. The resin cements were placed on dentin surfaces with the use of bonding agents. Shear bond strength (SBS) was tested using a single plane shear test assembly. The dentin specimens were divided into 10 groups. Eight groups were pre-treated with EDTA or phosphoric acid to remove the smear layer, followed by a bonding agent (Bond-1 or Single Bond) and resin cement (Rely X or Perma Cem). In the two remaining groups, the smear layer was left intact, and the two resins cements were used in combination with the self-etching bonding agent (Clearfil SE Bond). No statistically significant differences were observed among the eight groups treated with one-bottle bonding agents. The mean bond strengths of the two groups treated with the self-etching bonding agent did not differ significantly from each other but were both significantly greater than the bond strengths of all the other groups. The results of this study also showed that EDTA can be used as an alternative to phosphoric acid in bonding procedures for resin cements. However, the bond strengths of resin cements, in combination with a self-etching bonding agent, were significantly greater than those of the same cements when used with one-bottle bonding agents. PMID- 17288325 TI - Microtensile bond strength of resin composite bonded to caries-affected dentin with three adhesives. AB - This study evaluated the ability of two self-etching adhesives (a two-step and a one-step) and a conventional 3-step adhesive to bond composite to both intact and caries-affected dentin with and without thermocycling. Thirty extracted human teeth with occlusal caries were randomly assigned to three groups according to the adhesive used: Scotchbond Multi-purpose (3M) (SBMP), ClearfilSE Bond (Kuraray) (SE) and Xeno IV (Dentsply) (XEIV). The occlusal surfaces of the teeth were sectioned to expose dentin. The adhesives were applied according to manufacturers' instructions, and a composite material (Herculite XRV, Kerr) was applied and cured in increments to form a core 3 mm high. The teeth were stored in distilled water for 24 hours, then sectioned using a micro-slicing machine to obtain sections 1 mm thick. The sections were further cut to obtain rods 6 mm long and 1 x 1 mm in thickness, with dentin/composite interface located at the center. The specimens were examined microscopically to separate the caries affected (AD) and sound dentin (SD) into two groups. Half the specimens from each group were subjected to 3,000 thermocycles (5 degrees C to 55 degrees C) prior to testing. All the specimens were then subjected to microtensile bond strength (microTBS) testing in a special apparatus. Mean microTBS was determined for each group, and data were statistically analyzed with ANOVA and Tukey's tests. Mean microTBS and standard deviation values in MPa were: SBMP-SD = 22.19 (4.6), SBMP SD-thermocycled = 15.7 (5.55), SBMP-AD = 18.6 (2.89), SBMP-AD-thermocycled = 16.62 (6.23), SE-SD = 24.25 (5.7), SE-SD-thermocycled = 22.3 (6.7), SE-AD = 20.7 (5.55), SE-AD-thermocycled = 20.23 (6.1), XEIV-SD = 21.43 (7.6), XEIV-SD thermocycled = 18.3 (7.11), XEIV-AD = 15.45 (6.62), XEIV-AD-thermocycled = 14.8 (3.89). ANOVA revealed a significant difference among the groups (p < .0001). The two-step self-etch adhesive resulted in highest mean microTBS values under all test conditions. However, these mean values were significantly higher than the mean values obtained with the other two adhesives under some, but not all test conditions. PMID- 17288327 TI - Effect of curing mode on microtensile bond strength to dentin of two dual-cured adhesive systems in combination with resin luting cements for indirect restorations. AB - This study evaluated the microtensile bond strength (microTBS) of dual-cured adhesive systems when the different components were either light activated or left in the uncured state prior to cementation of an indirect composite restoration. Occlusal dentin surfaces of 40 human third molars were flattened. The teeth were randomly assigned to 8 groups (n = 5) according to the dual-cured systems (bonding agents/resin cements) and curing modes: All Bond 2/Duolink (AB2 BISCO Inc) and Optibond Solo Plus Dual Cure/Nexus 2 (SOLO-Kerr). Resin cements were applied to pre-cured resin composite discs (2 mm thick/Z-250/3M ESPE), which were fixed to dentin surfaces containing adhesive resin in either cured (LP) or uncured states (SP). The restored teeth were light activated according to the manufacturers' instructions (LRC-XL3000/3M ESPE) or allowed to self-cure (SRC). The restored teeth were water-stored at 37 degrees C for 24 hours. They were then both mesial-distally and buccal-lingually sectioned to obtain bonded specimens (1.2 mm2). Each specimen was tested in tension at a crosshead speed of 0.6 mm/minute until failure. Data (MPa (SD)) were analyzed by two-way ANOVA and Tukey's post-hoc test (p < .05). AB2/SP exhibited higher microTBS than AB2/LP (p = .00001); however, no significant differences were noted between SOLO/LP and SOLO/SP. Results suggested that dual-cured adhesive systems were as strong or even stronger when they were left in the uncured state prior to indirect resin composite cementation. PMID- 17288328 TI - Surface texture of four nanofilled and one hybrid composite after finishing. AB - This study evaluated the surface geometry of four nanocomposites and 1 hybrid composite after finishing with rigid rotary instruments. Four nanofilled composites (Premise, KerrHawe; Tetric EvoCeram, Ivoclar Vivadent; Filtek Supreme, 3M ESPE; Ceram X Duo, Dentsply) and one hybrid composite (Herculite XRV, KerrHawe) were used for the study. Sixty specimens were made of each product, 7 x 7 mm in size. Fifteen specimens of each composite were subjected to the following finishing procedures: a 30 microm diamond (FM 1), a sequence of a 30 microm and a 20 microm diamond (FM 2) and a 30 microm diamond followed by a 12-fluted tungsten carbide finishing bur (FM 3). As a reference, 15 other specimens of each material were treated with Sof-Lex discs. Evaluation of the surfaces was done with laser stylus profilometry. Roughness parameters were average roughness (Ra) and profile length ratio (LR). Statistical analysis of the data was performed by two-way and one-way ANOVA and post-hoc tests by Scheffe. Additional qualitative assessment of the finished composite surfaces was done by scanning electron microscopy (SEM) at a tension of 25 kV. The composite materials and the finishing methods had a significant effect on surface roughness (p < 0.001 for Ra and LR). There were significant interactions between the materials and the finishing methods (p < 0.001 for Ra and LR). Compared to Herculite XRV, three of the nanocomposites were significantly smoother after finishing, according to FM 1-3 and after application of the Sof-Lex discs. Ceram X Duo and Herculite XRV had similar surface roughness in terms of Ra and LR. Compared to a single 30 microm diamond and a sequence of two diamonds (FM 2), significantly lower roughness values on all composites were achieved by using a 30 microm diamond followed by a tungsten carbide instrument (p < 0.001 for Ra and LR). Ra- and LR-values after FM 3 were similar or, in some cases, even lower than surface roughness measured after application of Sof-Lex discs. Evaluation by SEM revealed that the use of a 30 microm diamond caused detrimental surface alteration on all types of composites. A remarkable number of porosities were detected on 1 of the nanofilled composites. PMID- 17288329 TI - Influence of water-storage time on the sorption and solubility behavior of current adhesives and primer/adhesive mixtures. AB - This study evaluated the effects of water-storage on the water sorption and solubility behavior of five commercially available dental adhesive systems and two primer/adhesive mixtures. The adhesives comprised three different approaches to bonding to hard tooth tissues: a one-step self-etching adhesive (One-up Bond F), two two-step self-etching primers (Clearfil SE Bond and Clearfil Protect Bond) and two etch-and-rinse systems: a water/ethanol-based (Single Bond) and an acetone-based filled adhesive (Prime&Bond NT). The bonding agents and primers of the two-step self-etching systems were mixed in a 1:1 volume ratio. Water sorption and solubility values were determined after 1, 7, 30, 90 and 180 days. The results showed that, except for SB, all adhesives presented increased water sorption with increased storage time. The one-step self-etching adhesive and self etching primer/adhesive mixtures presented the highest water sorption and solubility values. Equilibrium in the water sorption values was observed for all adhesives after 90 days of water-storage. However, solubility values continued to increase for some materials until 180 days. The sorption and solubility behavior of the materials tested seem to be related to hydrophilicity of the adhesive resin solution and might influence the long-term performance of resin-based composite restorations. PMID- 17288330 TI - Factors associated with microleakage in Class II resin composite restorations. AB - This in vitro study investigated the correlation between factors related to cavosurface marginal adaptation and microleakage in Class II cavities restored with a light- or chemical-activated resin composite. Standardized cavities were prepared in 40 molars that were randomly divided between both materials. Each of the groups was, in turn, divided, so that the restorations were placed by incremental and bulk techniques. The resultant four groups (n = 10), each with material/technique variations, had their marginal gaps measured by environmental scanning electron microscopy at randomly selected facial and lingual points of the proximal box of each restoration. After sectioning the teeth, interfacial dye penetration was assessed by light stereomicroscopy according to an ordinal scale at the same locations as for the marginal gaps. In a general linear model with microleakage as a dependent variable, no correlation between marginal gap size and microleakage was found (p = 0.802), although the interaction of the material and placement technique (p = 0.028) and material alone (p = 0.063) influenced microleakage. The model explained 63% of the variation in microleakage. It was concluded that, irrespective of the possible role of marginal gap in the occurrence of microleakage, the choice of material and placement technique are important determining factors in microleakage. PMID- 17288331 TI - Effect of single step adhesives on the marginal permeability of Class V resin composites. AB - This in vitro study evaluated the coronal and apical marginal microleakage of four self-etch, seventh generation adhesive systems. Sixty non-carious human molars were randomly assigned to four groups (n = 12). Class V cavities were prepared on the facial or lingual surface of each tooth with coronal margins in enamel and apical margins in cementum (dentin) at the cementoenamel junction. The preparations were restored using four self-etch adhesive systems (iBond, G-Bond, Xeno IV and Clearfil S3 Bond) and a control (no adhesive), followed by insertion of Gradia Direct microfilled hybrid resin composite. The teeth (specimens) were thermocycled 1,000 cycles, immersed in 1% methylene blue dye for 24 hours and invested in acrylic resin. The specimen blocks were then sectioned longitudinally, with dye penetration (microleakage) examined using a 20x binocular microscope. Coronal and apical margins were scored separately for microleakage using a 0-3 ordinal ranking system. Data were analyzed using non parametric tests at a p < 0.05 level of significance. A comparison of adhesive and control groups at the coronal and apical margins revealed that significant (p < .0001) differences were exhibited. At the coronal margin, Xeno IV revealed significantly less leakage than the other adhesives, with Clearfil S3 Bond exhibiting significantly less leakage at the apical margin. Groups with no adhesive treatment (control) showed significantly greater leakage at both the coronal and apical margin locations. A Wilcoxon signed rank test showed no significant differences at the coronal compared to the apical margins of the four adhesive systems and control tested. PMID- 17288332 TI - Influence of thermal cycling on dentin bond strengths of single-step self-etch adhesive systems. AB - This study investigated the influence of thermal cycling on the dentin bond strengths of single-step self-etch adhesive systems. The Absolute, Clearfil Tri-S Bond, G-Bond and One-Up Bond F Plus systems were used. Bovine mandibular incisors were mounted in self-curing resin, and the facial surfaces were wet ground with #600 SiC paper. Adhesives were applied to the prepared dentin surfaces, and they were light irradiated according to each manufacturer's instructions. Resin composites were condensed into a mold (4 mm in diameter and 2 mm in height) and light irradiated for 30 seconds. Bonded specimens were divided into three groups and subjected to different storage conditions as follows: 37 degrees C water for 24 hours; 37 degrees C water for 24 hours followed by 10,000 thermal cycles between 5 degrees C and 60 degrees C or 37 degrees C water for 24 hours followed by 20,000 thermal cycles between 5 degrees C and 60 degrees C. Ten samples per group were tested in a shear mode at a crosshead speed of 1.0 mm/minute. Analysis of variance and Tukey's HSD test at the 0.05 significance level were used to compare the three storage conditions for each adhesive system. After 24 hours storage in water, the mean dentin bond strengths ranged from 11.4 MPa to 17.1 MPa. The Clearfil Tri-S Bond system showed the highest bond strength. After 10,000 thermal cycles, the mean bond strengths remained unchanged except for those of the Clearfil Tri-S Bond system, which significantly increased. Significant decreases in bond strength were observed for the Absolute and One-Up Bond F Plus systems after 20,000 thermal cycles. Failure mode was commonly due to adhesive breakdown associated with partial cohesive failure of the adhesive resin. From the results of this study, in terms of simplifying the clinical procedure, the benefit of using single-step self-etch systems might be acceptable. PMID- 17288333 TI - Composite depth of cure obtained with QTH and LED units assessed by microhardness and micro-Raman spectroscopy. AB - This study analyzed the depth of cure of a composite assessed by microhardness and the degree of conversion as a function of the light cure unit (LCU) used. Two light cure units, one LED (Ultraled-Dabi Atlante) and one quartz-tungsten-halogen (QTH, Optilux 401-Demetron) unit were used to cure 4.0 x 4.0 mm and 5.0 mm deep composite specimens (Filtek Z250, 3M ESPE). After 24 hours storage at 37 degrees C, Knoop microhardness and degree of conversion were measured on the irradiated surface and at each millimeter of the sample's depth. The degree of conversion was determined by using micro-Raman spectroscopy. The specimens cured with the QTH unit presented uniform decay in microhardness up to 4 mm in depth. Beyond 4 mm, the drop was abrupt. With LED photoactivation, uniform decay was observed only up to 2 mm. At higher depths, the decay in microhardness increased rapidly, especially beyond 3 mm. Depth of cure assessed by micro-Raman revealed that the degree of conversion behaved similarly to microhardness for both LCUs. A strong linear regression between microhardness and the degree of conversion, including both LCUs, was established with R2 = 0.980. PMID- 17288334 TI - Influence of previous provisional cementation on the bond strength between two definitive resin-based luting and dentin bonding agents and human dentin. AB - This study evaluated the effect of two different types of provisional luting agents (RelyX Temp E, eugenol-based; RelyX Temp NE, eugenol-free) on the shear bond strengths between human dentin and two different resin-based luting systems (RelyXARC-Single Bond and Duo Link-One Step) after cementation with two different techniques (dual bonding and conventional technique). One hundred human molars were trimmed parallel to the original long axis, to expose flat dentin surfaces, and were divided into three groups. After related surface treatments for each specimen, the resin-based luting agent was applied in a silicone cylindrical mold (3.5 x 4 mm), placed on the bonding-agent-treated dentin surfaces and polymerized. In the control group (n = 20), the specimens were further divided into two groups (n = 10), and two different resin-based luting systems were immediately applied following the manufacturer's protocols: RelyX ARC-Single Bond (Group I C) and Duo Link-One Step (Group II C). In the provisionalization group (n = 40), the specimens were further divided into four subgroups of 10 specimens each (Group I N, I E and Group II N, II E). In Groups I N and II N, eugenol-free (RelyX NE), and in groups I E and II E, eugenol-based (RelyX E) provisional luting agents (PLA), were applied on the dentin surface. The dentin surfaces were cleaned with a flour-free pumice, and the resin-based luting systems RelyX ARC (Group I N and E) and Duo Link (Group II N and E) were applied. In the Dual bonding groups (n = 40), the specimens were divided into four subgroups of 10 specimens each (Group I ND, ED and Group II ND, ED). The specimens were treated with Single Bond (Groups I ND and ED) or One Step (Groups II ND and ED). After the dentin bonding agent treatment, RelyX Temp NE was applied to Groups I ND and II ND, and RelyX Temp E was applied to Groups I ED and II ED. The dentin surfaces were then cleaned as described in the provisionalization group, and the resin based luting systems were applied: RelyX ARC-Single Bond (Group I ND and ED) and Duo Link-One Step (Group II ND and ED). After 1,000 thermal cycles between 5 degrees C and 55 degrees C, shear bond testing was conducted at a crosshead speed of 0.5 mm/minutes. One-way ANOVA, followed by a post hoc Tukey test (alpha = 0.05) was done. The dentin-resin-based luting system interfaces were evaluated under a scanning electron microscope. There was a significant reduction in the mean shear bond strength values of groups subjected to the provisionalization compared to the control and dual bonding technique groups (p < 0.05). The composition of provisional luting did not create a significant difference with regard to reducing shear bond strength values (p > 0.05). With regard to resin based luting systems, the shear bond strength values of the double-bond technique groups were not significantly different from the controls (p > 0.05). PMID- 17288336 TI - American Academy of Gold Foil Operators Clinician of the Year award. Dr Daniel D Saucy. PMID- 17288335 TI - Composite veneering of complex amalgam restorations. AB - In large posterior cavities, indirect restorations could provide improved performance when compared to direct restorations, but with higher cost and removal of sound tooth structure. Improved mechanical properties have resulted in good clinical performance for amalgam in large cavities but without an esthetic appearance. Resin composites have become popular for posterior restorations, mainly because of good esthetic results. A restorative technique is presented that combines the esthetic properties of directly bonded resin composite and the wide range of indications for amalgam in stress-bearing areas. PMID- 17288337 TI - American Academy of Gold Foil Operators Distinguished Member Award. Dr Allan G Osborn. PMID- 17288339 TI - [New scientific arguments for further reducing the use of tobacco, also in the hotel, restaurant and catering business]. AB - The prohibition of smoking in public places that has been implemented in various European countries has led to a noticeable decrease in the number of hospital admissions for acute myocardial infarction. This effect became manifest within one year after the adoption of the measure. A significant proportion of the benefit can probably be ascribed to the reduction of passive smoking. The recently published INTERHEART study is a case-control study involving approximately 12,500 patients who had been admitted for an acute myocardial infarction and approximately 14,500 apparently healthy controls. The study was carried out in 52 countries and reveals that an increased risk of acute myocardial infarction as the result of tobacco use can be seen in all investigated countries and races. Smoking as well as the chewing or sniffing of tobacco are associated with an increased risk; there is also a clear proportional relationship between the level of tobacco use and the degree of risk. Moreover, passive smoking was again shown to be an important and avoidable cause ofacute myocardial infarction. In the Netherlands, smoking in public buildings has been prohibited since 1990, with the exception of the hotel, restaurant and catering industry. It would be a good thing if this exception were eliminated in our country as well. PMID- 17288338 TI - [Fatigue, loss of appetite and anuria due to retroperitoneal fibrosis]. AB - Two men aged 58 and 76, respectively, presented with fatigue and loss of appetite followed by anuria. Laboratory tests showed anaemia, elevated ESR and renal failure. CT of the abdomen revealed obstruction of the ureters by retroperitoneal fibrosis. The first patient had retroperitoneal fibrosis in combination with an aneurysm of the aorta; in the second patient, the image was suggestive of pancreatic carcinoma with secondary fibrosis, but eventually the retroperitoneal fibrosis proved to be idiopathic. Both patients were successfully treated with prednisone and temporary placement ofnephrostomy catheters. Retroperitoneal fibrosis is an often idiopathic disease that can cause compression of retroperitoneal structures such as the ureters. The clinical picture is aspecific so that the diagnosis is often delayed. Treatment with prednisone is preferable, followed by immunosuppressive therapy or tamoxifen in case of resistance to steroids. Relief of the obstruction by means of temporary nephrostomy catheters often makes surgery unnecessary. Retroperitoneal fibrosis is an uncommon disease that deserves more attention in view ofthe favourable therapeutic options following timely diagnosis. PMID- 17288340 TI - [Prevention of neonatal infection with group B streptococci: what the best strategy is remains unclear]. AB - Early-onset group B streptococcal disease (GBS disease) is an important cause of morbidity and mortality in newborn infants. There is no international agreement on the best strategy for selecting pregnant women for antibiotic prophylaxis during delivery in order to reduce the incidence of this disease. A cost effectiveness study of 4 strategies using a theoretical model showed that the risk strategy (antibiotics for women at risk) and combination strategy (antibiotics for GBS-positive women at risk) seemed more cost-effective than the current Dutch strategy (antibiotics for women at risk ifGBS positive) and the screening strategy (antibiotics for GBS-positive women). Balancing the possible effects, costs, unwanted side effects, and limitations of the implementation of either strategy in the Netherlands, the combination strategy may be a reasonable option. The possibly favourable introduction of PCR screening techniques and vaginal chlorhexidine flushing in Dutch obstetric practice deserves further scientific attention. PMID- 17288341 TI - [Vaccination against pneumococci and hepatitis B in the Dutch National Immunisation Programme]. AB - All infants in the Netherlands, which are born after March 2006, receive additional vaccinations at the age of 2, 3, 4 and 11 months to protect them against pneumococcal infections. During the same visit to a consultation bureau, the children also receive a combination vaccine against diphtheria, pertussis, tetanus, poliomyelitis and Haemophilus influenzae (DTPa-IPV-Hib). Children of which at least one parent was born in a country where hepatitis B occurs relatively often are also vaccinated in the Netherlands against hepatitis B. This currently pertains to about 15% of all newborns. These children now receive a new combination vaccine in which a hepatitis B component has been added to the DTPa IPV-Hib components. They will receive this combination vaccine 4 times. This combination vaccine is given during the same visit as the pneumococcal vaccination. Although pneumococcal vaccination may have a somewhat negative effect on the immune response to hepatitis B, it is expected that the new 4-fold vaccination schedule will induce good and long-lasting protection against hepatitis B in the vast majority of the children. About 700 children are born out of mothers infected with hepatitis B each year in the Netherlands. In the new vaccination schedule, they now receive 5 active vaccinations against hepatitis B and are examined serologically on an individual basis in order to detect breakthrough infections. This will also generate greater insight into the efficacy of the different vaccination schemes and intervention programmes to prevent vertical transmission of the virus. PMID- 17288342 TI - [A combined protocol using CT, CT perfusion and CT angiography for the evaluation of cerebral ischemia]. AB - Computed tomography (CT) is a widely available, rapid and readily accessible technique for imaging of the brain by means of which other disorders, such as haemorrhage, can be excluded in patients with the signs of an acute cerebral infarction. Recently, CT perfusion and CT angiography have become available for this clinical application. These investigations can be performed in the same session as conventional CT, without significant delay. A combined CT protocol provides information on both cerebral perfusion and the patency of the extra- and intracranial arteries and can therefore yield valuable additional information in the diagnostic work-up and treatment of patients with acute cerebral ischaemia. Current and future research will have to determine the definitive value of these techniques in clinical practice. PMID- 17288343 TI - [Diagnostic image (307). A man with dysphagia]. AB - A 51-year-old man suffered from longstanding dysphagia due to a large aneurysm of the thoracoabdominal aorta. PMID- 17288344 TI - [From gene to disease; the haemolytic uraemic syndrome can be caused by mutations in regulating factors of the alternative route of the complement system]. AB - Defective control of the alternative route of the complement system is an important cause of the non-diarrhoea haemolytic uraemic syndrome (HUS). On the endothelial surface, mutations in HF1, MCP and IF predispose to development ofHUS. Uncontrolled complement activation on the surface of endothelial cells will damage these cells extensively. Plasmapheresis can be an effective, although temporary, treatment for mutations in HF1 and IF. HUS frequently recurs after renal transplantation in patients with HF1 or IF mutations but not in patients with a mutation of MCP. These genetic defects can be detected by routine diagnostics. PMID- 17288346 TI - [Serious complications following removal of an ingested partial denture]. AB - Complications occurred in a 41-year-old woman following an attempt to remove a partial denture by oesophagoscopy. These were: laceration of the oesophagus with subsequent mediastinitis, pneumothorax, and pneumopericardium. At a second oesophagoscopy the denture was removed from the oesophagus using a flexible hood. Following antibiotic treatment the patient recovered. In a 45-year-old man who had also swallowed a denture, the denture could not initially be localized. It was eventually recovered from the antrum using a flexible scope with a flexible hood. The patient was discharged from hospital in a good condition. Psychiatric and mentally handicapped patients run a high risk of denture ingestion. Ingested dental prostheses are often radiolucent, and are difficult to visualize using radiological methods. Extraction of the ingested foreign objects can lead to severe complications. This is why in this type of case, we recommend the use of a flexible scope and a flexible hood attachment. PMID- 17288347 TI - [Indications for respiratory complications during the use of oral nifedipine as a tocolytic agent, especially in patients with multiple pregnancies]. AB - In 7 women with premature labour pains, severe dyspnoea developed that was possibly related to the use of nifedipine as an 'off-label' tocolytic. 6 of these women had a twin pregnancy. Diuretics and oxygen therapy had little effect, but the patients recovered after the administration of nifedipine was stopped. The efficacy and safety of nifedipine as a tocolytic agent has been investigated in a number of well-designed randomised studies. However, these studies were performed in a selected group of pregnant women and women with multiple pregnancies or prematurely ruptured membranes were mostly excluded. It can be hypothesised that the respiratory complications in these cases are due to unequal ventilation/perfusion of the lungs in the presence of a physiologically elevated diaphragm due to the pregnancy. These changes are more pronounced in multiple pregnancies. After administration ofnifedipine, there is perfusion of atelectatic areas of the lung that are not or not well ventilated, resulting in ventilation perfusion discrepancy and hence dyspnoea. Although case reports permit only limited extrapolation, these observations warrant caution with regard to the safety ofnifedipine as a tocolytic agent in patients with multiple pregnancies. The use of medication in groups of patients for which the agent has not been investigated, or which were explicitly excluded from the study, should be done with extreme caution. One should in any case be aware of the possible risks. PMID- 17288348 TI - [Bloodletting; a popular form of treatment that disappeared]. AB - Bloodletting, based on the humoural pathology of Hippocrates and Galen, was done in various ways for thousands of years: phlebotomy, cupping and the use of leeches. There were broad indications for applying this form of treatment. In the 19th century, P.C.A. Louis demonstrated that bloodletting was not an optimal form of treatment for pneumonia. His study was designed in accordance with the first principles of epidemiology. Epidemiology, together with the rise of Virchow's cellular pathology, contributed to the disappearance of bloodletting. The use of leeches still has a place in the medicine of the 21st century in the form of enzymes from the saliva of the leech. PMID- 17288350 TI - Tories may 'guarantee' work for new nurses. PMID- 17288349 TI - [Central congenital hypothyroidism due to Graves' disease in the mother]. PMID- 17288351 TI - Revolution in post-op nursing. AB - Hospital care at home is common practice in the United States and Australia. Now the practice is coming to the UK and can benefit patients, nurses and cash strapped trusts. PMID- 17288352 TI - Putting all the pieces together. AB - The move to a competence-based work system is investigated in the third article on the Modernising Nursing Careers: Setting the Direction document. PMID- 17288353 TI - Talking history. AB - Nurses' voices rarely feature when hospital histories are written. But an oral history project has captured the stories of more than 100 nurses from St George's Hospital, London. PMID- 17288354 TI - Pressing for action. PMID- 17288355 TI - Improving ward management. AB - This article describes the development, implementation and evaluation of an audit process--the nursing annual audit review--to improve nursing management systems on wards in a large NHS foundation trust. It is set in the context of healthcare governance and improving the quality of services provided by healthcare organisations. PMID- 17288356 TI - An overview of probiotics and prebiotics. AB - This article reviews the origins and background of probiotics. Evidence for the potential mechanisms of probiotics and prebiotics, and their interactions with the gastrointestinal tract and the immune system are discussed. Evidence is examined for the use of probiotics to treat infantile diarrhoea, irritable bowel syndrome, inflammatory bowel disease and atopic dermatitis. PMID- 17288358 TI - Clinical learning. PMID- 17288357 TI - Healthy Start: improving maternal, infant and child health. AB - Maternal health during pregnancy and children's nutrition in their early years can affect their future health. This article explains how health professionals can promote the health of future generations by informing low-income, vulnerable and excluded families about the government's Healthy Start scheme and by encouraging breastfeeding and sharing information on how mothers, infants and children can have a healthy diet and lifestyle. PMID- 17288359 TI - Can you tell write from wrong? PMID- 17288360 TI - The nurse is not for burning. PMID- 17288361 TI - Hydrogen-mediated C-C bond formation: a broad new concept in catalytic C-C coupling. PMID- 17288362 TI - Synthesis and structural and photoswitchable properties of novel chiral host molecules: axis chiral 2,2'-dihydroxy-1,1'-binaphthyl-appended stiff-stilbene. AB - Novel photoswitchable chiral hosts having an axis chiral 2,2'-dihydroxy-1,1' binaphthyl (BINOL)-appended stiff-stilbene, trans-(R,R)- and -(S,S)-1, were synthesized by palladium-catalyzed Suzuki-Miyaura coupling and low-valence titanium-catalyzed McMurry coupling as key steps, and they were fully characterized by various NMR spectral techniques. The enantiomers of trans-1 showed almost complete mirror images in the CD spectra, where two split Cotton effects (exciton coupling) were observed in the beta-transitions of the naphthyl chromophore at 222 and 235 nm, but no Cotton effect was observed in the stiff stilbene chromophore at 365 nm. The structures of (R)-10 and trans-(R,R)-1 were confirmed by X-ray structural analysis. The optimized structure of cis-1 by MO calculations has a wide chiral cavity of 7-8 A in diameter, whereas trans-1 cannot form an intramolecular cavity based on the X-ray data. Irradiation of (R,R)-trans-1 with black light (lambda = 365 nm) in CH3CN or benzene at 23 degrees C led to the conversion to the corresponding cis-isomer, as was monitored by 1H NMR, UV-vis, and CD spectra. At the photostationary state, the cis-1/trans 1 ratio was 86/14 in benzene or 75/25 in CH3CN. On the other hand, irradiation of the cis-1/trans-1 (75/25) mixture in CH3CN with an ultra-high-pressure Hg lamp at 23 degrees C (lambda = 410 nm) led to the photostationary state, where the cis 1/trans-1 ratio was estimated to be 9/91 on the basis of the 1H NMR spectra. The cis-trans and trans-cis interconversions could be repeated 10 times without decomposition of the C=C double bond. Thus, a new type of photoswitchable molecule has been developed, and trans-1 and cis-1 were quite durable under irradiation conditions. The guest binding properties of the BINOL moieties of trans- and cis-(R,R)-1 with F-, Cl-, and H2PO4- were examined by 1H NMR titration in CDCl3. Similar interaction with F- and Cl- was observed in trans-1 (host/guest = 1/1, Kassoc = (1.0 +/- 0.13) x 103 for F- and (4.6 +/- 0.72) x 102 M-1 for Cl-) and cis-1 (host/guest = 1/1, Kassoc = (1.0 +/- 0.13) x 103 for F- and (5.9 +/- 0.69) x 10 M-1 for Cl-), but H2PO4- interacted differently: the cis-isomer formed the 1/1 complex (Kassoc = (9.38 +/- 2.67) x 10 M-1), whereas multistep equilibrium was expected for the trans-isomer. PMID- 17288363 TI - Ketene-forming elimination reactions from aryl thienylacetates promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq). Effect of the beta-aryl group. AB - Ketene-forming eliminations from ArCH2CO2C6H3-2-X-4-NO2 (Ar = thienyl, 1) promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq) have been studied kinetically. When X = CF3 and NO2, the reactions exhibit second-order kinetics as well as beta = 0.30-0.64 and |betalg| = 0.31-0.52 that decrease with a better leaving group. Hence, an E2 mechanism is evident. As the leaving group is made poorer (X = H, OCH3, and Cl), E2 transition state becomes more skewed toward the proton transfer, as revealed by the increase in Bronsted beta to 0.5-0.64, and the E1cb mechanism competes. The changes in the k1 and k-1/k2 values with the reactant structure variation provide additional support for the competing E1cb mechanism. By comparing with existing data for 4-YC6H4CH2CO2C6H3-2-X-4-NO2, the effect of beta-aryl group on ketene-forming elimination is assessed. PMID- 17288364 TI - Effect of substitution on the intramolecular 1,3-dipolar cycloaddition of alkene tethered munchnones. AB - A sequence of chemoselective activation of N-acylaminoacids, munchnone generation, intramolecular 1,3-dipolar cycloaddition, and ring opening efficiently generated functionalized polycyclic structures such as cyclopenta[b]pyrroles or zwitterionic bicyclo[4.3.0]nonane or bicyclo[3.3.0]octanes in one operation is given. These zwitterionic species were isolated for the first time and were subsequently reduced to bicyclic aminoalcohols. The effect of the substitution of both the dipolarophile and the munchnone on the intramolecular cycloaddition outcome was examined. It was found that either nonactivated or electron-poor alkenes can react with the munchnone if these alkenes are tethered at position 4 on the munchnone (2, R2 = alkene tether), whereas only an electron-poor alkene at position 2 (2, R3 = alkene tether) could undergo successful cycloaddition. Also, munchnones substituted at position 2 with a phenyl (2, R3 = Ph) showed a dramatic increase in reactivity, whereas a phenyl at position 4 (2, R2 = Ph) had a very limited effect. PMID- 17288365 TI - Cyclization of 1,5-dienes: an efficient synthesis of beta-Georgywood. AB - In the acid-promoted 1,5-diene cyclization of pseudo- to beta-Georgywood, the cyclization product is obtained with high selectivity in spite of an unfavorable substituent at the C(2)-position of the diene precursor. Preisomerization of the cyclohexene double bond, which occurs in the presence of Bronsted acids, is suppressed with >1 equiv of MXn-type Lewis acids, whereas RAlX2-type Lewis acids such as >2 equiv of MeAlCl2 have the additional benefit of steering the double bond of the cyclized product into the desired beta-position. Mechanistic studies revealed a crucial participation or nonparticipation of the carbonyl group in the cyclization reaction, depending on the acid family employed, and allowed finally the development of a cyclization reaction catalyzed by MeAlCl2 that can be generated in situ from precatalyst AlMe3.1. PMID- 17288366 TI - Desaturase reactions complicate the use of norcarane as a mechanistic probe. Unraveling the mixture of twenty-plus products formed in enzyme-catalyzed oxidations of norcarane. AB - Norcarane, bicyclo[4.1.0]heptane, has been widely used as a mechanistic probe in studies of oxidations catalyzed by several iron-containing enzymes. We report here that, in addition to oxygenated products, norcarane is also oxidized by iron containing enzymes in desaturase reactions that give 2-norcarene and 3-norcarene. Furthermore, secondary products from further oxidation reactions of the norcarenes are produced in yields that are comparable to those of the minor products from oxidation of the norcarane. We studied oxidations catalyzed by a representative spectrum of iron-containing enzymes including four cytochrome P450 enzymes, CYP2B1, CYPDelta2B4, CYPDelta2E1, and CYPDelta2E1 T303A, and three diiron enzymes, soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath), toluene monooxygenase (ToMO) from Pseudomonas stutzeri OX1, and phenol hydroxylase (PH) from Pseudomonas stutzeri OX1. 2-Norcarene and 3 norcarene and their oxidation products were found in all reaction mixtures, accounting for up to half of the oxidation products in some cases. In total, more than 20 oxidation products were identified from the enzyme-catalyzed reactions of norcarane. The putative radical-derived product from the oxidation of norcarane, 3-hydroxymethylcyclohexene (21), and the putative cation-derived product from the oxidation of norcarane, cyclohept-3-enol (22), coelute with other oxidation products on low-polarity GC columns. The yields of product 21 found in this study are smaller than those previously reported for the same or similar enzymes in studies where the products from norcarene oxidations were ignored, and therefore, the limiting values for lifetimes of radical intermediates produced in the enzyme catalyzed oxidation reactions are shorter than those previously reported. PMID- 17288368 TI - Polycyclic benzenoids: why kinked is more stable than straight. AB - The enhanced stability of bent or kinked polycyclic benzenoids over linear ones is well established, phenanthrene and anthracene being archetypal representatives. The question why kinked is more stable than linear is, however, still a matter of discussion. Recently, it has been proposed that H-H bonding interactions between the two hydrogen atoms in the bay region of phenanthrene are responsible for the larger stability of this molecule as compared to anthracene. This conclusion conflicts with the vast body of evidence for nonbonded steric repulsion between these hydrogen atoms. In this work, we provide new, complementary evidence for the repulsive character of the H-H interactions in phenanthrene's bay region. We have traced the origin of phenanthrene's enhanced stability to the more efficient bonding in the pi-electron system using, among others, a quantitative energy decomposition analysis of the bonding between the two constituting 2-methtriyl-phenyl fragments in both phenanthrene and anthracene (i.e., C14H10 = C6H4*-CH** + C6H4*-CH**). The scope of our study is extended to polycyclic benzenoids by analyzing also hexacene and various bent isomers of the latter. Our results once more falsify one of the core concepts of the theory of atoms-in-molecules (AIM), namely, that the presence of bond paths and the presence of bond critical points (they exist indeed between the two bay H atoms in phenanthrene) are sufficient indicators for a stabilizing interaction. Instead, our results confirm that these AIM parameters merely diagnose the proximity or contact between charge distributions, be this contact stabilizing or destabilizing. PMID- 17288367 TI - Products from enzyme-catalyzed oxidations of norcarenes. AB - Recent studies revealed that norcarane (bicyclo[4.1.0]heptane) is oxidized to 2 norcarene (bicyclo[4.1.0]-hept-2-ene) and 3-norcarene (bicyclo[4.1.0]hept-3-ene) by iron-containing enzymes and that secondary oxidation products from the norcarenes complicate mechanistic probe studies employing norcarane as the substrate (Newcomb, M.; Chandrasena, R. E. P.; Lansakara-P., D. S. P.; Kim, H. Y.; Lippard, S. J.; Beauvais, L. G.; Murray, L. J.; Izzo, V.; Hollenberg, P. F.; Coon, M. J. J. Org. Chem. 2007, 72, 1121-1127). In the present work, the product profiles from the oxidations of 2-norcarene and 3-norcarene by several enzymes were determined. Most of the products were identified by GC and GC-mass spectral comparison to authentic samples produced independently; in some cases, stereochemical assignments were made or confirmed by 2D NMR analysis of the products. The enzymes studied in this work were four cytochrome P450 enzymes, CYP2B1, CYPDelta2E1, CYPDelta2E1 T303A, and CYPDelta2B4, and three diiron containing enzymes, soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath), toluene monooxygenase (ToMO) from Pseudomonas stutzeri OX1, and phenol hydroxylase (PH) from Pseudomonas stutzeri OX1. The oxidation products from the norcarenes identified in this work are 2-norcaranone, 3-norcaranone, syn and anti-2-norcarene oxide, syn- and anti-3-norcarene oxide, syn- and anti-4 hydroxy-2-norcarene, syn- and anti-2-hydroxy-3-norcarene, 2-oxo-3-norcarene, 4 oxo-2-norcarene, and cyclohepta-3,5-dienol. Two additional, unidentified oxidation products were observed in low yields in the oxidations. In matched oxidations, 3-norcarene was a better substrate than 2-norcarene in terms of turnover by factors of 1.5-15 for the enzymes studied here. The oxidation products found in enzyme-catalyzed oxidations of the norcarenes are useful for understanding the complex product mixtures obtained in norcarane oxidations. PMID- 17288369 TI - Calorimetric and computational study of 1,3- and 1,4-oxathiane sulfones. AB - The enthalpies of formation in the condensed and gas states, DeltafH degrees m(cd) and DeltafH degrees m(g), of 1,3- and 1,4-oxathiane sulfones were derived from their respective enthalpies of combustion in oxygen, measured by a rotating bomb calorimeter and the variation of vapor pressures with temperatures determined by the Knudsen effusion technique. Standard ab initio molecular orbital calculations at the G2(MP2) and G3 levels were performed, and a theoretical study on molecular and electronic structure of the compounds has been carried out. Calculated DeltafH degrees m(g) values at the G3 level using atomization reactions agree well with the experimental ones. These experimental and theoretical studies support that the destabilization found in 1,3-oxathiane sulfone, 11.2 kJ mol-1 respecting to 1,4-oxathiane sulfone, is due to the electrostatic repulsion between the negative charges of the axial oxygen of the sulfone and the oxygen of the ring and apparently masks any stabilization originating from the hyperconjugative nO --> sigma*C-SO2 stereoelectronic interaction. PMID- 17288370 TI - 26pi aromatic core-modified hexaphyrins: syntheses, characterization, and structural diversities. AB - Synthesis and characterization of several 26pi core-modified hexaphyrins are reported. The synthetic methodology involved a well-known acid-catalyzed MacDonald-type condensation reaction of the required tripyrrane with electron deficient pentafluorobenzaldehyde. The nature of the product and yield depends on the nature of the acid catalyst and its concentration. Dioxahexaphyrin 9 was isolated only when 0.5 equiv of TFA was used as a catalyst, while dithiahexaphyrin 10 and diselenahexaphyrin 11 were formed with TFA, PTSA, and even in the absence of catalyst. The detailed 1H and 2-D COSY as well as HSQC experiments reveal the solution structure as well as the conformational mobility of hexaphyrins. In the tetracationic state, 10 and 11 exhibit a four heterocyclic ring inverted structure, while only two completely inverted heterocyclic rings were observed for 9. The other four heterocyclic rings are only partially inverted in 9. All the hexaphyrins reported here show aromatic character inferred from large Deltadelta values (difference in chemical shift between the most shielded and the most deshielded protons). Electronic absorption spectral studies also support the conformational changes observed upon protonation. PMID- 17288371 TI - Multifunctional ferrocene-ruthenocene dyads linked by single or double aza containing bridges displaying metal-metal interactions and cation recognition properties. AB - The synthesis, electrochemical, electronic, and cation sensing properties of the ruthenocene-terminated 2-aza-1,3-butadiene 2, linear ferrocene-ruthenocene dyads 3 and 5, and the new structural motifs diaza[4.4]ruthenocenophane 7 and mixed ferrocene and ruthenocene metallocenophanes 8 and 10 are presented. The properties of these compounds have been systematically varied by introducing the ferrocene and ruthenocene moieties at the 1- or 4-position of the unsymmetrical 2 aza-1,3-butadiene bridge. Spectroelectrochemical studies of compounds 3 and 8, in which the ruthenocene unit appended at the 1-position of the bridge exhibits a rather unusual electrochemical behavior, revealed the presence of low-energy bands in the near-infrared (NIR) region in the partially oxidized forms, at 1070 and 1163 nm, respectively, which indicate the existence of intramolecular charge transfer between the iron and the ruthenium centers. The electrochemical and intermetallic charge-transfer (MMCT) studies (HAB, lambda and alpha parameters) indicate that the 3*+ and 8*+ systems belong to the Class II classification for a mixed-valence compound. In addition, the low-energy (LE) band of the absorption spectra of all compounds prepared, except compound 10, are red-shifted by complexation with divalent Mg2+, Zn2+, Cd2+, Hg2+, and Ni2+ metal ions. For open dyads, biruthenocene compound 2 exhibited the higher red-shift by 92 nm, whereas for closed compounds the [4.4]ruthenocenoferrocenophane 8 displayed a remarkable red-shift by about 180 nm for Zn2+, Cd2+, Hg2+, and Ni2+ metal ions and by about 146 nm for Mg2+ cation. The changes in the absorption spectra are accompanied by dramatic color changes which allow the potential for "naked eye" detection. The experimental data and conclusions are supported by DFT computations. PMID- 17288372 TI - Au-catalyzed reaction of propargylic sulfides and dithioacetals. AB - Propargylic sulfides and dithioacetals are found to undergo similar transformations as propargylic carboxylates when catalyzed by AuCl or AuCl3, affording indene derivatives through pentannulation of aromatic rings. The reaction presumably involves Au carbene as the reactive intermediate. PMID- 17288373 TI - Synthesis of 2'-C-alpha-(hydroxyalkyl) and 2'-C-alpha-alkylcytidine phosphoramidites: analogues for probing solvent interactions with RNA. AB - Nucleoside analogues bearing 2'-C-alpha-(hydroxyalkyl) and 2'-C-alpha-alkyl substitutes have numerous applications in RNA chemistry and biology. In particular, they provide a strategy to probe the interaction between the 2' hydroxyl group of RNA and water. To incorporate these nucleoside analogues into oligonucleotides for studies of the group II intron (Gordon, P. M.; Fong, R.; Deb, S.; Li, N.-S.; Schwans, J. P.; Ye, J.-D.; Piccirilli, J. A. Chem. Biol. 2004, 11, 237), we synthesized six new phosphoramidite derivatives of 2'-deoxy-2' C-alpha-(hydroxyalkyl)cytidine (36: R = -(CH2)2OH; 38: R = -(CH2)3OH; 40: R = (CH2)4OH) and 2'-deoxy-2'-C-alpha-alkylcytidine (37: R = -CH2CH3; 39: R = (CH2)2CH3; 41: R = -(CH2)3CH3) from cytidine or uridine via 2'-C-alpha allylation, followed by alkene and alcohol transformations. Phosphoramidites 36 and 37 were prepared from cytidine in overall yields of 14% (10 steps) and 7% (11 steps), respectively. Phosphoramidites 38 and 39 were prepared from uridine in overall yields of 30% (10 steps) and 13% (11 steps), respectively. Phosphoramidites 40 and 41 were synthesized from uridine in overall yields of 21% (13 steps) and 25% (14 steps), respectively. PMID- 17288374 TI - Convenient synthesis of unsymmetrical organochalcogenides using organoboronic acids with dichalcogenides via cleavage of the S-S, Se-Se, or Te-Te bond by a copper catalyst. AB - This article describes the methodology for a copper-catalyzed preparation of numerous monochalcogenides from dichalcogenides with organoboronic acids. Unsymmetrical diorgano-monosulfides, selenides, and tellurides can be synthesized by the coupling of dichalcogenides with aryl- or alkylboronic acids using a copper catalyst in air. The present reaction can take advantage of both organochalcogenide groups on dichalcogenide. PMID- 17288375 TI - Triflic acid-catalyzed additions of 2-alkoxycarbonyl allylboronates to aldehydes. Study of scope and mechanistic investigation of the reaction stereochemistry. AB - The substrate scope and the effect of substrate on the observed inversion of stereoselectivity in the triflic acid-catalyzed allylboration reaction between 2 alkoxycarbonyl allylboronates and aldehydes are presented. A mechanistic investigation is described so as to confirm the involvement of a carbocation intermediate as the source of stereochemical inversion. This methodology allows a facile access to beta,gamma-disubstituted five-membered ring lactones with an exo methylene at the alpha-position. PMID- 17288376 TI - Kinetics of the reactions of [p nitrophenoxy(phenyl)carbene]pentacarbonylchromium(0) with aryloxide ions, hydroxide ion, and water in aqueous acetonitrile. Concerted or stepwise? AB - The main question addressed in this paper is whether the nucleophilic substitution of the p-nitrophenoxy group in (CO)5Cr=C(OC6H4-4-NO2)Ph (1-NO2) by a series of substituted phenoxide ions is concerted or stepwise. Rate constants, kArO, for these substitution reactions were determined in 50% MeCN-50% water (v/v) at 25 degrees C. A Bronsted plot of log kArO versus pKa(ArOH) s consistent with a stepwise mechanism. This contrasts with reactions of aryl oxide ions with p-nitrophenyl acetate and with similar acyl transfers which are concerted. The reason for the contrast is that the tetrahedral intermediates formed in the reactions of 1-NO2 are much more stable than those in acyl transfers and the intrinsic barriers to their decomposition are higher than for the ester reactions. The points on the Bronsted plots for which pKa(ArOH) > or = pKa(PNP) define a straight line with beta(nuc) = -0.39, suggesting that bond formation has made very little progress at the transition state and that partial desolvation of the nucleophile is part of the activation process. The hydrolysis of 1-NO2 and of the unsubstituted analogue (1-H) has also been studied over a wide pH range, providing rate constants for nucleophilic attack by hydroxide ion (kOH), by water (kH2O), and by general base-catalyzed reaction with water (kB). Furthermore, kH2O values were obtained for the hydrolysis of (CO)5Cr=C(OC6H4X)Ph (1-X) as a byproduct of the reactions of 1-NO2 with aryl oxide ions. Structure-reactivity relationships for these reactions are discussed in terms of inductive, pi-donor, and steric effects. PMID- 17288377 TI - Lewis acid mediated asymmetric [2,3]-sigmatropic rearrangement of allylic amines. Scope and mechanistic investigation. AB - The first asymmetric [2,3]-sigmatropic rearrangement of achiral allylic amines has been realized by quaternization of the amines with an enantiomerically pure diazaborolidine and subsequent treatment with Et3N. The resultant homoallylic amines were obtained in good yields and excellent ee's. The observed diastereo- and enantioselectivities were rationalized by invoking a kinetically controlled process, and support for this model was obtained from an NMR spectroscopic investigation of the chiral Lewis acid-substrate complex. The structure of the Lewis acid-product complex was established by X-ray crystallographic analysis and supported the proposed mechanism. PMID- 17288378 TI - A biocatalytic approach to synthesizing optically active orthogonally protected trans-cyclopentane-1,2-diamine derivatives. AB - A straightforward chemoenzymatic synthesis of optically active trans-N,N dialkylcyclopentane-1,2-diamines has been efficiently developed starting out from their analogous (+/-)-trans-2-(N,N-dialkylamino)cyclopentanols. The route involves the one-pot stereospecific transformation of the racemic amino alcohols into racemic diamines and a subsequent kinetic resolution by means of lipase-B from Candida antarctica-catalyzed acylation reactions. The careful selection of both the alkyl substituents present in the diamine and the derivatization strategy applied to the enzymatic reaction enabled the easy preparation of other synthetically valuable optically active trans-cyclopentane-1,2-diamines derivatives. PMID- 17288379 TI - Organocatalysis with a fluorous tag: asymmetric reduction of imines with trichlorosilane catalyzed by amino acid-derived formamides. AB - Asymmetric reduction of ketimines 1 with trichlorosilane can be catalyzed by N methylvaline-derived Lewis-basic formamides 3a-d with high enantioselectivity (< or =95% ee) and low catalyst loading (1-5 mol %) at room temperature in toluene. Appending a fluorous tag, as in 5a-c, simplifies the isolation procedure, while preserving high enantioselectivity (< or =92% ee). PMID- 17288380 TI - Reaction of electron-deficient N=N, N=O double bonds, singlet oxygen, and CC triple bonds with acyloxyketenes or mesoionic 1,3-dioxolium-4-olates: generation of unstable mesoionic 1,3-dioxolium-4-olates from acyloxyketenes. AB - Reactions of azodicarboxylates and nitrosobenzene derivatives with acyloxyketenes generated from dehydrochlorination of alpha-acyloxyarylacetyl chlorides were carried out to give triacylbenzamidine and N-arylimide derivatives, respectively, in good yields. The same compounds were obtained from the reaction with mesoionic 1,3-dioxolium-4-olates generated by Rh2(OAc)4-catalyzed decomposition of aryldiazoacetic anhydride derivatives. Formation of the same compounds from the different starting materials indicates that their reactions involve the same intermediates. The formation of triacylbenzamidine and N-arylimide derivatives is explained by 1,3-dipolar cycloaddition between electron-deficient N=N or N=O bonds and mesoionic 1,3-dioxolium-4-olates following by decarboxylation, ring opening of the resultant carbonyl ylides, and subsequent Mumm rearrangement of the corresponding imidates. The reaction with singlet oxygen composed of more electronegative atoms than N=N and N=O bonds also gave products arising from the singlet oxygen adducts with 1,3-dioxolium-4-olates. The generation of less stable mesoionic 1,3-dioxolium-4-olates from acyloxyketenes was also confirmed by isolation of furandicarboxylates on generation of acyloxyketenes from alpha acyloxyarylacetyl chlorides in the presence of reactive dipolarophile dimethyl acetylenedicarboxylate. PMID- 17288381 TI - Tetrahydrothiophene-catalyzed synthesis of benzo[n.1.0] bicycloalkanes. AB - A catalytic intramolecular cyclopropanation for the preparation of benzobicyclic compounds with [n.1.0] units has been developed. In the presence of 20 mol % of tetrahydrothiophene, the reactions of compounds 2a-2h afford versatile benzo[n.1.0]bicycloalkanes with excellent stereoselectivity in moderate to good isolated yields. PMID- 17288382 TI - Synthesis of 3,4-disubstituted 2H-benzopyrans through C-C bond formation via electrophilic cyclization. AB - The electrophilic cyclization of substituted propargylic aryl ethers by I2, ICl, and PhSeBr produces 3,4-disubstituted 2H-benzopyrans in excellent yields. This methodology results in vinylic halides or selenides under mild reaction conditions and tolerates a variety of functional groups, including methoxy, alcohol, aldehyde, and nitro groups. PMID- 17288384 TI - Domino carbocationic rearrangement of alpha-[bis(methylthio)methylene]alkyl-2 (3/2-indolyl) cyclopropyl ketones. AB - Domino carbocationic rearrangement of a number of substituted 3- and 2 indolylcyclopropyl ketones with an alpha-bis(methylthio)methylene group in the presence of various protic/Lewis acids yields a variety of products, mainly the pentaleno fused indoles and the carbazole derivatives. PMID- 17288383 TI - Syntheses of novel chiral sulfinamido ligands and their applications in diethylzinc additions to aldehydes. AB - A novel class of sulfinamido alcohol ligands 1-6 was synthesized from (S)-tert butanesulfinamide. These ligands showed excellent catalytic activities and enantiomeric selectivities in asymmetric additions of diethylzinc to aromatic aldehydes. PMID- 17288385 TI - A new route to highly functionalized heterocyclic rings. AB - A novel cascade reaction has been developed for the rapid construction of heterocyclic rings. The cyclization is thermally induced and does not involve the use of metal ions. This highly efficient construction of furans has been developed during studies directed toward the synthesis of the antibiotic lactonamycin 1. PMID- 17288386 TI - Synthesis of a stereochemically defined 1,2-diazetine N,N'-dioxide and a study of its thermal decomposition. AB - Diazetine dioxide 1a has been synthesized in a single step via oxidation of meso 2,3-diphenyl-1,2-ethanediamine with dimethyldioxirane, albeit in low yield (7%). Thermal decomposition of 1a afforded predominantly either trans-stilbene or diphenyl glyoxime depending on solvent, temperature, and the presence of an amine catalyst. Reaction in chloroform at 69 degrees C favored elimination of NO and formation of trans-stilbene. The stereospecific formation of trans-stilbene suggests a mechanism of decomposition in which C-N bond cleavage leads to a diradical intermediate stabilized by the phenyl group. Bond rotation followed by cleavage of the second C-N bond accounts for the trans-stilbene. At 25 degrees C in chloroform, while trans-stilbene was still the major product, some diphenyl glyoxime was also observed (4% yield). However, 1a as a solution in chloroform in the presence of Et3N, or 1a as a solution in DMSO-d6, afforded predominantly diphenyl glyoxime. These results are interpreted in terms of two closely competing reactions subject to the effects of entropic contributions. PMID- 17288387 TI - Microwave-assisted asymmetric organocatalysis. A probe for nonthermal microwave effects and the concept of simultaneous cooling. AB - A series of five known asymmetric organocatalytic reactions was re-evaluated at elevated temperatures applying both microwave dielectric heating and conventional thermal heating in order to probe the existence of specific or nonthermal microwave effects. All transformations were conducted in a dedicated reactor setup that allowed accurate internal reaction temperature measurements using fiber-optic probes. In addition, the concept of simultaneous external cooling while irradiating with microwave power was also applied in all of the studied cases. This method allows a higher level of microwave power to be administered to the reaction mixture and, therefore, enhances any potential microwave effects while continuously removing heat. For all of the five studied (S)-proline catalyzed asymmetric Mannich- and aldol-type reactions, the observed rate enhancements were a consequence of the increased temperatures attained by microwave dielectric heating and were not related to the presence of the microwave field. In all cases, in contrast to previous literature reports, the results obtained either with microwave irradiation or with microwave irradiation with simultaneous cooling could be reproduced by conventional heating at the same reaction temperature and time in an oil bath. No evidence for specific or nonthermal microwave effects was obtained. PMID- 17288388 TI - Mechanism of metal chloride-promoted Mukaiyama aldol reactions. AB - Ab initio calculations (MP2/6-311+G**//B3LYP/6-31G*) were employed to investigate the mechanism of metal chloride-promoted Mukaiyama aldol reaction between trihydrosilyl enol ether and formaldehyde. The metal chlorides considered include TiCl4, BCl3, AlCl3, and GaCl3. In contrast to the concerted pathway of the uncatalyzed aldol reaction, the Lewis acid-promoted reactions favor a stepwise mechanism. Three possible stepwise pathways were located. The lowest energy pathway corresponds to a simultaneous C-C bond formation and a chlorine atom shift in the first (rate-determining) step. This process is calculated to have a low activation barrier of 12 kJ mol-1 for the TiCl4-promoted reaction. The alternative [2+2] cycloaddition and direct carbon-carbon bond formation pathways are energetically competitive. BCl3, AlCl3, and GaCl3 are predicted to be efficient catalysts for the silicon-directed aldol reaction as they strongly activate the formaldehyde electrophile. Formation of a stable pretransition state intermolecular pi-pi complex between enol silane and the activated formaldehyde (CH2=O...MCln) is a key driving force for the facile metal chloride-promoted reactions. PMID- 17288389 TI - DFT-based mechanism for the unexpected formation of dienes in the PtCl2 isomerization of propargylic acetates: examples of inhibition of the Rautenstrauch process. AB - The reactivity of the Pt(II)-mediated processes of unsaturated compounds strongly depends on the substrate structure, and the catalytic activation process may follow different reaction paths, such as skeletal rearrangements, cyclizations, and isomerizations. Herein, we analyze and report the striking effect of an ester group as an alkyne substituent on the reactivity of propargylic enynes, which has been shown to inhibit the expected Rautenstrauch process. The computed results agree with experimental evidence and provide a comprehensible rationalization. PMID- 17288390 TI - Organocatalytic cascade reactions based on push-pull dienamine platform: synthesis of highly substituted anilines. AB - A practical and novel one-pot organocatalytic selective process for the cascade synthesis of highly substituted o-hydroxydiarylamines and o-pyrrolidin-1 yldiarylamines is reported. Direct combination of amine-catalyzed cascade Knoevenagel/Michael/aldol condensation/decarboxylation and cascade enamine amination/isoaromatization of alkyl acetoacetates, aldehydes, and nitrosoarenes furnished the highly functionalized anilines with high yields. PMID- 17288391 TI - A novel strategy for the preparation of naturally occurring phosphocitrate and its partially esterified derivatives. AB - A novel method for the synthesis of phosphocitrate (1, PC) starting from triethyl ester of citric acid and MeOPCl2 is described. The method is based on selective stepwise hydrolysis of ester moieties from the intermediate Me-O-P(O)(Cl)(Z) (Z = triethylcitrate), 4a, which also allows one to prepare partially esterified derivatives of PC with good yield and purity without chromatographic purifications. PMID- 17288393 TI - In-plane aromaticity in double group transfer reactions. AB - The main features of double group transfer reactions have been studied under the density-functional theory framework. It is found that a wide range of structure types and processes including type II-dyotropic reactions and the Meerwein Ponndorf-Verley reduction take place via highly synchronous in-plane aromatic transition structures. Actually, the orbital topology of these saddle points is equivalent to that which corresponds to a D2h-symmetric aromatic molecule such as pyrazine. PMID- 17288392 TI - Phosphine-free palladium-catalyzed C-H bond arylation of free (N-H)-indoles and pyrroles. AB - This paper describes a phosphine-free palladium-catalyzed method for direct C arylation of free (N-H)-indoles and pyrroles with iodo- and bromoarene donors. Employing commercially available materials, this new and operationally simple procedure provides a rapid entry to a wide range of C-arylated (N-H)-indoles including derivatives of tryptamine. In the course of this study, a profound halide effect was uncovered, affecting both the efficiency and regioselectivity of indole arylation. PMID- 17288394 TI - Reagent-dependent regioselective control in multiple carbohydrate esterifications. AB - Regioselective control in organotin-mediated multiple acylation of carbohydrates is presented. The acylation reagent could be efficiently used to direct the product formation. Reagent-dependent thermodynamic and kinetic control and dynamic assistance mechanisms are suggested, resulting in the efficient preparation of building blocks that normally require many steps with traditional synthesis. PMID- 17288395 TI - Template effects in the formation of [2]pseudo-rotaxanes containing diazapyrenium units. AB - The template effects exerted by guests 14 and 15 in the ring closure reaction of 3 have been quantitatively evaluated. The rate largely increases in the presence of the two templates. The results are compared with those relative to the ring closure reaction of 1 yielding cyclobis(paraquat-p-phenylene), 2. The comparison indicates that the formation of tetracationic aromatic cycles templated by aromatic donors benefits from the use of extended pi surfaces both in the acceptor and in the donor components. PMID- 17288396 TI - Unexpected 1,5-dilithiation of chiral o-TMS blocked (dimethylamino)phenylmethylferrocene: an alternative approach to chiral ferrocenyl 1,5-diphosphanes. AB - The 1,5-dilithiation of o-TMS blocked (dimethylamino)phenylmethylferrocene 4 unexpectedly occurred even though one equimolar amount of t-BuLi was used and the 1,5-dilithiated ferrocene 6 was trapped by iodine followed by removal of the TMS group to give the 1,5-diiodoferrocene 11 in a reasonable yield. The 1,5 diiodoferrocene 11 was converted into the diastereomer of Taniaphos 12 by sequential dilithiation and trapping with Ph2PCl. The rhodium and copper complex of 12 catalyzed well the asymmetric allylic alkylation with a Grignard reagent and hydrogenation with the alpha-acetamidocinnamic acid ester, respectively, with high enantioselectivities. The methoxy 1,5-diphosphane 14, of which the enantiomer is known as a good ligand for the rhodium-catalyzed asymmetric hydrogenation, was obtained by the inversive substitution of the dimethylamino group of 11 by NaOMe and subsequent dilithiation and trapping with Ph2PCl. PMID- 17288397 TI - 2-Trimethylsilylethanesulfonyl (SES) versus tosyl (Ts) protecting group in the preparation of nitrogen-containing five-membered rings. A novel route for the synthesis of substituted pyrrolines and pyrrolidines. AB - The 2-trimethylsilylethanesulfonyl (or SES) protecting group was compared to the tosyl (Ts) group in the preparation of a nitrogen-containing five-membered ring obtained by the aza-Baylis-Hillman/alkylation/RCM route. While deprotection of Ts protected pyrrolines gave only pyrroles, deprotection of the same SES-protected compounds gave either pyrroles or free amine pyrrolines depending on the deprotection conditions. The SES-protected pyrrolines were hydrogenated to yield pyrrolidines with an excellent diastereoselectivity. Free amine pyrrolidines were obtained by HF-mediated deprotection of the SES group. PMID- 17288398 TI - Enantioselective amination of alpha-phenyl-alpha-cyanoacetate catalyzed by chiral amines incorporating the alpha-phenylethyl auxiliary. AB - Nineteen chiral amines and their derivatives were prepared and investigated as organocatalytic Lewis bases in the alpha-amination of ethyl alpha-phenyl-alpha cyanoacetate. For comparison purposes, a few natural products were also examined as catalysts in this study. Among the results obtained, (R)-N-benzyl-N-(1 phenylethyl)-amine and (R,R)-N,N'-bis(1-phenylethyl)-propane-1,3-diamine as the catalysts afforded the amination products in excellent yields and with up to 84% ee. By contrast, under comparable conditions the two derivatives of natural products (DHQ)2PYR and (DHQD)2PYR provided the product of amination with lower than 10% enantiomeric excess. PMID- 17288399 TI - Intramolecular PIFA-mediated alkyne amidation and carboxylation reaction. AB - The hypervalent iodine reagent PIFA promotes the intramolecular electrophilic cyclization of easily accessible alkynylamides and alkynyl carboxylic acids, leading to the formation of pyrrolidinone and lactone skeletons, respectively, in a very efficient way. A synthetic study and a mechanistic proposal for these transformations are presented. PMID- 17288400 TI - Reaction of allenyl esters with sodium azide: an efficient synthesis of e-vinyl azides and polysubstituted pyrroles. AB - The nucleophilic addition of sodium azide to 1,2-allenyl esters can generate vinyl azides in excellent yields with excellent regio- and stereoselectivities. Moreover, pyrroles are synthesized using 1-allyllic 1,2-allenyl esters as substrates in t-BuOH at 65 degrees C. The sequential reaction for pyrroles is developed on the basis of a novel domino process involving nucleophilic addition, cycloaddition, denitrogenation, and aromatization. PMID- 17288401 TI - Palladium-catalyzed carboannulation of propargylic carbonates and nucleophiles to 2-substituted indenes. AB - A new and efficient synthesis of 2-substituted indenes has been achieved via palladium-catalyzed carboannulation of propargylic carbonates with nucleophiles in good to excellent yields. A variety of nucleophiles were tolerated in this reaction. PMID- 17288402 TI - A tetramethoxybenzophenone as efficient triplet photocatalyst for the transformation of diazo compounds. AB - The aromatic ketone 2,2',4,4'-tetramethoxybenzophenone has a strong absorption band between 300 and 375 nm, and its pi,pi* triplet excited-state is selectively populated in methanol. Both facts make this aromatic ketone a versatile and efficient triplet photocatalyst for the transformation of alpha-diazo carbonyl compounds into mainly the cyclopropanation product. PMID- 17288403 TI - Rate-limiting hydrodynamic resistance for controlled reagent delivery for laboratory solution preparation. AB - The need for precise delivery of minute quantities of substances for solution preparation and other applications is well-known in research, clinical, industrial, and environmental settings. Currently available techniques for solution preparation in the laboratory include traditional transfer pipettes, micropipettes based on air displacement, and motorized devices using some form of a piston system. These techniques control the amount delivered by controlling the delivered volume. In this work we test the practicality of the concept of using a constant rate-limiting hydrodynamic resistance to achieve controlled reagent flow for solution preparation. The delivered amount is determined in this approach by time, pressure, flow resistance, or a combination of these. Good results are achieved comparable to conventional techniques without the use of fine mechanical instrumentation. This approach holds promise as an alternative to current methods of solution preparation and reagent delivery for routine laboratory use. PMID- 17288404 TI - Stochastic sensing on a modular chip containing a single-ion channel. AB - Engineered protein channels have many potential applications in biosensing at the single-molecule level. A future generation of biosensor could be an array of target-specific ion channels, where each protein pore acts as a sensor element. An important step toward this goal is to create a portable, durable, single protein channel-integrated chip device. Here we report a versatile, modular chip that contains a single-ion channel for single-molecular biosensing. The core of the device is a long-lived lipid membrane that has been sandwiched between two air-insulated agarose layers which gel in situ. A single-protein pore embedded in the membrane serves as the sensor element. The modular device is highly portable, allowing a single-ion channel to continuously function following detachment of the chip from the instrument and independent transportation of the device. The chip also exhibits high durability, which is evidenced from long-duration continuous observation of single-channel dynamics. Once engineered protein pores are installed, the chip becomes a robust stochastic sensor for real-time targeting such as detection of the second messenger IP3. This pluggable biochip could be incorporated with many applicable devices, such as a microfluidic system, and be made into a microarray for both biomedical detection and membrane protein research. PMID- 17288405 TI - Magnetophoretic immunoassay of allergen-specific IgE in an enhanced magnetic field gradient. AB - We demonstrate a novel magnetophoretic immunoassay of allergen-specific immunoglobulin E (IgE) based on the magnetophoretic deflection velocity of a microbead that is proportional to the associated magnetic nanoparticles under enhanced magnetic field gradient in a microchannel. In this detection scheme, two types of house dust mites, Dermatophagoides farinae (D. farinae) and Dermatophagoides pteronyssinus (D. pteronyssinus), were used as the model allergens. Polystyrene microbeads were conjugated with each of the mite extracts followed by incubation with serum samples. The resulting mixture was then reacted with magnetic nanoparticle-conjugated anti-human IgE for detection of allergen specific IgE by using sandwich immuno-reactions. A ferromagnetic microstructure combined with a permanent magnet was employed to increase the magnetic field gradient ( approximately 10(4) T/m) in a microfluidic device. The magnetophoretic velocities of microbeads were measured in a microchannel under applied magnetic field, and the averaged velocity was well correlated with the concentration of allergen-specific IgE in serum. From the analysis of pooled sera obtained from 44 patients, the detection limits of the allergen-specific human IgEs for D. farinae and D. pteronyssinus were determined to be 565 (0.045 IU/mL) and 268 fM (0.021 IU/mL), respectively. These values are 1 order of magnitude lower than those by a conventional CAP system. For evaluation of reproducibility and accuracy, unknown sera were subjected to a blind test by using the developed assay system, and they were compared with the CAP system. As a result, coefficient of variance was less than 10%, and the developed method enabled a fast assay with a tiny amount of serum ( approximately 10 microL). PMID- 17288406 TI - Fluorescence determination of nitric oxide production in stimulated and activated platelets. AB - Nitric oxide (NO) is quantitatively determined in platelets prior to, and after, stimulation with adenosine triphosphate (ATP) or activation with adenosine diphosphate (ADP). Platelets obtained from the whole blood of rabbits were loaded with the fluorescence probe diaminodifluorofluorescein diacetate (DAF-FM DA), and the subsequent NO production was measured as a fluorescent benzotriazole. Experiments were performed to determine the effect of probe concentration and probe incubation time in the platelets prior to measurement of the fluorescence. This information, combined with the method of multiple standard additions, was then employed to determine the moles of intracellular NO in the platelets (2.7 +/ 0.3) x 10(-16) mol of NO/platelet and the basal level of extracellular NO in the platelet sample (9.9 +/- 2.2) x 10(-18) mol of NO/platelet. Moreover, this method was used to quantitatively determine the amount of NO released from platelets whose NO production was stimulated with ATP (a nitric oxide synthase stimulus) or ADP, a substance known to result in NO production through platelet aggregation. When stimulated with ATP, the NO released from the platelets was determined to be (2.0 +/- 0.1) x 10(-17) mol of NO/platelet. When activated with ADP, the platelets released (2.8 +/- 0.3) x 10(-17) mol of NO/platelet. The difference between the extracellular basal levels of NO and that after stimulation with either ATP or ADP is in agreement with current estimates of NO release from platelets. Therefore, we conclude that a fluorescence determination of NO using the DAF family of probes, in combination with the method of multiple standard additions, can be employed to quantitatively determine the basal levels of NO in platelets, as well as the amount of NO released from stimulated and/or activated platelets. PMID- 17288408 TI - Application of global kinetic models to HMX beta-delta transition and cookoff processes. AB - The reduction of the number of reactions in kinetic models for both the HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) beta-delta phase transition and thermal cookoff provides an attractive alternative to traditional multi-stage kinetic models due to reduced calibration effort requirements. In this study, we use the LLNL code ALE3D to provide calibrated kinetic parameters for a two reaction bidirectional beta-delta HMX phase transition model based on Sandia instrumented thermal ignition (SITI) and scaled thermal explosion (STEX) temperature history curves, and a Prout-Tompkins cookoff model based on one dimensional time to explosion (ODTX) data. Results show that the two-reaction bidirectional beta-delta transition model presented here agrees as well with STEX and SITI temperature history curves as a reversible four-reaction Arrhenius model yet requires an order of magnitude less computational effort. In addition, a single-reaction Prout-Tompkins model calibrated to ODTX data provides better agreement with ODTX data than a traditional multistep Arrhenius model and can contain up to 90% fewer chemistry-limited time steps for low-temperature ODTX simulations. Manual calibration methods for the Prout-Tompkins kinetics provide much better agreement with ODTX experimental data than parameters derived from differential scanning calorimetry (DSC) measurements at atmospheric pressure. The predicted surface temperature at explosion for STEX cookoff simulations is a weak function of the cookoff model used, and a reduction of up to 15% of chemistry limited time steps can be achieved by neglecting the beta-delta transition for this type of simulation. Finally, the inclusion of the beta-delta transition model in the overall kinetics model can affect the predicted time to explosion by 1% for the traditional multistep Arrhenius approach, and up to 11% using a Prout Tompkins cookoff model. PMID- 17288407 TI - Synthesis, stability, and cellular internalization of gold nanoparticles containing mixed peptide-poly(ethylene glycol) monolayers. AB - Gold nanoparticles have shown great promise as therapeutics, therapeutic delivery vectors, and intracellular imaging agents. For many biomedical applications, selective cell and nuclear targeting are desirable, and these remain a significant practical challenge in the use of nanoparticles in vivo. This challenge is being addressed by the incorporation of cell-targeting peptides or antibodies onto the nanoparticle surface, modifications that frequently compromise nanoparticle stability in high ionic strength biological media. We describe herein the assembly of poly(ethylene glycol) (PEG) and mixed peptide/PEG monolayers on gold nanoparticle surfaces. The stability of the resulting bioconjugates in high ionic strength media was characterized as a function of nanoparticle size, PEG length, and monolayer composition. In total, three different thiol-modified PEGs (average molecular weight (MW), 900, 1500, and 5000 g mol-1), four particle diameters (10, 20, 30, and 60 nm), and two cell-targeting peptides were explored. We found that nanoparticle stability increased with increasing PEG length, decreasing nanoparticle diameter, and increasing PEG mole fraction. The order of assembly also played a role in nanoparticle stability. Mixed monolayers prepared via the sequential addition of PEG followed by peptide were more stable than particles prepared via simultaneous co-adsorption. Finally, the ability of nanoparticles modified with mixed PEG/RME (RME = receptor-mediated endocytosis) peptide monolayers to target the cytoplasm of HeLa cells was quantified using inductively coupled plasma optical emission spectrometry (ICP OES). Although it was anticipated that the MW 5000 g mol-1 PEG would sterically block peptides from access to the cell membrane compared to the MW 900 PEG, nanoparticles modified with mixed peptide/PEG 5000 monolayers were internalized as efficiently as nanoparticles containing mixed peptide/PEG 900 monolayers. These studies can provide useful cues in the assembly of stable peptide/gold nanoparticle bioconjugates capable of being internalized into cells. PMID- 17288409 TI - Calculations of the optical spectra of hydrocarbon radical cations based on Koopmans' theorem. AB - The first few bands in the optical spectra of radical cations can often be interpreted in terms of A-type transitions that involve electron promotions from doubly occupied to the singly occupied molecular orbital (SOMO) and/or B-type transition which involve electron promotion from the SOMO to virtual molecular orbitals. We had previously demonstrated that, by making use of Koopmans' theorem, the energies of A-type transitions can be related to orbital energy differences between lower occupied MOs and the highest occupied MO (HOMO) in the neutral molecule, calculated at the geometry of the radical cation. We now propose that the energies of B-type transitions can be related similarly to energy differences between the lowest unoccupied MO (LUMO) and higher virtual MOs in the dication, also calculated at the geometry of the radical cation, by way of an extension of Koopmans' theorem to virtual MOs similar to that used sometimes to model resonances in electron scattering experiments. The optical spectra of the radical cations of several polyenes and aromatic compounds, the matrix spectra of which are known (or presented here for the first time), and for which CASSCF/CASPT2 calculations are available, are discussed in terms of these Koopmans-based models. Then the spectra of five poly(bicycloalkyl)-protected systems and that of hexabenzocoronene, compounds not amenable to higher level calculations, are examined and it is found that the Koopmans-type calculations allow a satisfactory interpretation of most of the features in these spectra. These simple calculations therefore provide a computationally inexpensive yet effective way to assign optical transitions in radical ions. Limitations of the model are discussed. PMID- 17288410 TI - Inversed stability order in Keggin polyoxothiometalate isomers: a DFT study of 12 electron reduced alpha, beta, gamma, delta, and epsilon [(MoO4)Mo12O12S12(OH)12]2 anions. AB - Density functional theory calculations have been carried out to investigate 12 electron reduced alpha, beta, gamma, delta, and epsilon Keggin-like [(MoO4)Mo12O12S12(OH)12]2- polyoxothiometalates (POTMs), which show that the stability order is alpha < beta < gamma < delta < epsilon that is perfectly inverse to the well-known trend of the classical Keggin polyoxometalates. Energy decomposition analysis reveals that the enhanced stabilities of gamma, delta, and epsilon isomers originate the favorable arrangements of their Mo12O12S12(OH)12 shell, in which the edge-sharing [MoV2(mu-S)2O2] fragment plays a fundamental role in stabilizing the overall structure. Both frontier orbital analysis and Mayer indexes exhibit that a Mo-Mo single bond is formed inside the [MoV2(mu S)2O2] fragment, which leads to the localization of the two reduced electrons. As compared with experimentally discovered cyclic [(C9H3O6)@Mo12O12S12(OH)12]3-, all Keggin POTM structures are less stable due to their disfavored cage framework and the disadvantageous host-guest interaction. However, the epsilon-type Keggin POTM that has the largest similarity to the cyclic species is possibly available in the presence of appropriate templates. PMID- 17288411 TI - Energetics of C-F, C-Cl, C-Br, and C-I bonds in 2-haloethanols. enthalpies of formation of XCH(2)CH(2)OH (X = F, Cl, Br, I) compounds and of the 2-hydroxyethyl radical. AB - The energetics of the C-F, C-Cl, C-Br, and C-I bonds in 2-haloethanols was investigated by using a combination of experimental and theoretical methods. The standard molar enthalpies of formation of 2-chloro-, 2-bromo-, and 2-iodoethanol, at 298.15 K, were determined as Delta(f)H(degree)m(CH2CH2OH, l) = -315.5 +/- 0.7 kJ.mol-1, Delta(f)H(degree)mBrCH2CH2OH, l) = -275.8 +/- 0.6 kJ.mol-1, Delta(f)H(degree)m(ICH2CH2OH, l) = -207.3 +/- 0.7 kJ.mol-1, by rotating-bomb combustion calorimetry. The corresponding standard molar enthalpies of vaporization, Delta(vap)H(degree)m(ClCH2CH2OH) = 48.32 +/- 0.37 kJ.mol-1, Delta(vap)H(degree)m(BrCH2CH2OH) = 54.08 +/- 0.40 kJ.mol-1, and Delta(vap)H(degree)m(ICH2CH2OH) = 57.03 +/- 0.20 kJ.mol-1 were also obtained by Calvet-drop microcalorimetry. The condensed phase and vaporization enthalpy data lead to Delta(f)H(degree)m(ClCH2CH2OH, g) = -267.2 +/- 0.8 kJ.mol-1, Delta(f)H(degree)m(BrCH2CH2OH, g) = -221.7 +/- 0.7 kJ.mol-1, and Delta(f)H(degree)m(ICH2CH2OH, g) = -150.3 +/- 0.7 kJ.mol-1. These values, together with the enthalpy of selected isodesmic and isogyric gas-phase reactions predicted by density functional theory (B3LYP/cc-pVTZ) and CBS-QB3 calculations were used to derive the enthalpies of formation of gaseous 2-fluoroethanol, Delta(f)H(degree)m(FCH2CH2OH, g) = -423.6 +/- 5.0 kJ.mol-1, and of the 2 hydroxyethyl radical, Delta(f)H(degree)m(CH2CH2OH, g) = -28.7 +/- 8.0 kJ.mol-1. The obtained thermochemical data led to the following carbon-halogen bond dissociation enthalpies: DHo(X-CH2CH2OH) = 474.4 +/- 9.4 kJ.mol-1 (X = F), 359.9 +/- 8.0 kJ.mol-1 (X = Cl), 305.0 +/- 8.0 kJ.mol-1 (X = Br), 228.7 +/- 8.1 kJ.mol 1 (X = I). These values were compared with the corresponding C-X bond dissociation enthalpies in XCH2COOH, XCH3, XC2H5, XCH=CH2, and XC6H5. In view of this comparison the computational methods mentioned above were also used to obtain Delta(f)H(degree)m-594.0 +/- 5.0 kJ.mol-1 from which DHo(F-CH2COOH) = 435.4 +/- 5.4 kJ.mol-1. The order DHo(C-F) > DHo(C-Cl) > DHo(C-Br) > DHo(C-I) is observed for the haloalcohols and all other RX compounds. It is finally concluded that the major qualitative trends exhibited by the C-X bond dissociation enthalpies for the series of compounds studied in this work can be predicted by Pauling's electrostatic-covalent model. PMID- 17288412 TI - Evaluating virtual screening methods: good and bad metrics for the "early recognition" problem. AB - Many metrics are currently used to evaluate the performance of ranking methods in virtual screening (VS), for instance, the area under the receiver operating characteristic curve (ROC), the area under the accumulation curve (AUAC), the average rank of actives, the enrichment factor (EF), and the robust initial enhancement (RIE) proposed by Sheridan et al. In this work, we show that the ROC, the AUAC, and the average rank metrics have the same inappropriate behaviors that make them poor metrics for comparing VS methods whose purpose is to rank actives early in an ordered list (the "early recognition problem"). In doing so, we derive mathematical formulas that relate those metrics together. Moreover, we show that the EF metric is not sensitive to ranking performance before and after the cutoff. Instead, we formally generalize the ROC metric to the early recognition problem which leads us to propose a novel metric called the Boltzmann enhanced discrimination of receiver operating characteristic that turns out to contain the discrimination power of the RIE metric but incorporates the statistical significance from ROC and its well-behaved boundaries. Finally, two major sources of errors, namely, the statistical error and the "saturation effects", are examined. This leads to practical recommendations for the number of actives, the number of inactives, and the "early recognition" importance parameter that one should use when comparing ranking methods. Although this work is applied specifically to VS, it is general and can be used to analyze any method that needs to segregate actives toward the front of a rank-ordered list. PMID- 17288413 TI - Carboxylate coordination chemistry of a mononuclear Ni(II) center in a hydrophobic or hydrogen bond donor secondary environment: relevance to acireductone dioxygenase. AB - A series of Ni(II) carboxylate complexes, supported by a chelate ligand having either secondary hydrophobic phenyl groups (6-Ph2TPA, N,N-bis((6-phenyl-2 pyridyl)methyl)-N-((2-pyridyl)methyl)amine) or hydrogen bond donors (bnpapa, N,N bis((6-neopentylamino-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine), have been prepared and characterized. X-ray crystallographic studies of [(6 Ph2TPA)Ni(O2C(CH2)2SCH3)]ClO4.CH2Cl2 (4.CH2Cl2) and [(6 Ph2TPA)Ni(O2CCH2SCH3)]ClO(4).1.5CH2Cl2 (5.1.5CH2Cl2) revealed that each complex contains a distorted octahedral Ni(II) center and a bidentate carboxylate ligand. A previously described benzoate complex ([(6-Ph2TPA)Ni(O2CPh)]ClO4 (3)) has similar structural characteristics. Recrystallization of dry powdered samples of 3, 4.0.5CH2Cl2, and 5 from wet organic solvents yielded a second series of crystalline Ni(II) carboxylate complexes having a coordinated monodentate carboxylate ligand ([(6-Ph2TPA)Ni(H2O)(O2CPh)]ClO4 (6), [(6 Ph2TPA)Ni(H2O)(O2C(CH2)2SCH3)]ClO4.0.2CH2Cl2 (7.0.2CH2Cl2), [(6 Ph2TPA)Ni(H2O)(O2CCH2SCH3)]ClO4 (8)) which is stabilized by a hydrogen-bonding interaction with a Ni(II)-bound water molecule. In the cationic portions of 7.0.2CH2Cl2 and 8, weak CH/pi interactions are also present between the methylene units of the carboxylate ligands and the phenyl appendages of the 6-Ph2TPA ligands. A formate complex of the formulation [(6-Ph2TPA)Ni(H2O)(O2CH)]ClO4 (9) was isolated and characterized. The mononuclear Ni(II) carboxylate complexes [(bnpapa)Ni(O2CPh)]ClO4 (10), [(bnpapa)Ni(O2C(CH2)2SCH3)]ClO4 (11), [(bnpapa)Ni(O2CCH2SCH3)]ClO4 (12), and [(bnpapa)Ni(O2CH)]ClO4 (13) were isolated and characterized. Two crystalline solvate forms of 10 (10.CH3CN and 10.CH2Cl2) were examined by X-ray crystallography. In both, the distorted octahedral Ni(II) center is ligated by a bidentate benzoate ligand, one Ni(II)-bound oxygen atom of which accepts two hydrogen bonds from the supporting bnpapa chelate ligand. Spectroscopic studies of 10(-13) suggest that all contain a bidentate carboxylate ligand, even after exposure to water. The combined results of this work enable the formulation of a proposed pathway for carboxylate product release from the active site Ni(II) center in acireductone dioxygenase. PMID- 17288414 TI - Energy-resolved collision-induced dissociation cross sections of 2:1 bis oxazoline copper complexes. Nonbonded interactions and nonlinear effects. AB - Absolute ligand binding energies are determined for the 2:1 complexes of bis oxazoline ligands and Cu(I) in the gas phase by the fitting of energy-resolved collision-induced dissociation cross sections. The complexes were chosen for their occurrence in asymmetric catalysis for which the phenomenon of nonlinear effects is explained by differences in stability for homochiral and heterochiral complexes. Pseudo-enantiomeric ligands are used so that mass spectrometric measurements can be employed. The measurements find that the sterically similar, but electronically different, isopropyl versus phenyl substituents lead to a different stability ordering of the homo- versus heterochiral complexes, which then leads to the prediction of nonlinear effects in asymmetric catalysis by the complexes with isopropyl-substituted ligands. The origin of the difference in stability order is found in noncovalent interactions between the phenyl groups on the ligands, which are poorly described by DFT calculations. PMID- 17288415 TI - Dynamic recompartmentalization of supported lipid bilayers using focused femtosecond laser pulses. PMID- 17288416 TI - Effect of deuterium on the kinetics of 1,5-hydrogen shifts: 5-dideuteriomethylene 2,4,6,7,9-pentamethyl-11,11a- dihydro-12H-naphthacene. AB - To obtain a more reliable temperature dependence of the kinetic deuterium isotope effect in a 1,5-hydrogen shift, the title compound has been designed to repress compromising side reactions, arguably arising from second-order ene-ene unions. The values of kH/kD, 4.58-5.15, in the range 185.8-153.8 degrees C, on extrapolation by the derived Arrhenius equation, lead to 8-14 at 25 degrees C. Another goal is the evaluation of the effect on rates of the free rotation available to the phenyl groups in 2,4-diphenyl-1,3(Z)-pentadiene compared to the constraint to coplanarity of the phenyl groups in the title compound. The effect is insignificant. Incidental to the presence of the sterically effective methyl groups in the title compound, participation of the hydrogen atoms of an aromatic methyl group as part of the 1,3(Z)-pentadienyl system has been uncovered in 6,8 dimethyl-1-methylene-1,2,3,4-tetrahydronaphthalene. The rate of the rearrangement is too slow to compromise the kinetics of the hydrogen shifts in the title compound. A reassessment of the conventional procedure for estimating uncertainties in Arrhenius parameters based on a small number of rate constants has led to the proposal of an alternative procedure based on the statistically more significant uncertainties associated with the individual rate constants. PMID- 17288418 TI - Classification of water molecules in protein binding sites. AB - Water molecules play a crucial role in mediating the interaction between a ligand and a macromolecular receptor. An understanding of the nature and role of each water molecule in the active site of a protein could greatly increase the efficiency of rational drug design approaches: if the propensity of a water molecule for displacement can be determined, then synthetic effort may be most profitably applied to the design of specific ligands with the displacement of this water molecule in mind. In this paper, a thermodynamic analysis of water molecules in the binding sites of six proteins, each complexed with a number of inhibitors, is presented. Two classes of water molecules were identified: those conserved and not displaced by any of the ligands, and those that are displaced by some ligands. The absolute binding free energies of 54 water molecules were calculated using the double decoupling method, with replica exchange thermodynamic integration in Monte Carlo simulations. It was found that conserved water molecules are on average more tightly bound than displaced water molecules. In addition, Bayesian statistics is used to calculate the probability that a particular water molecule may be displaced by an appropriately designed ligand, given the calculated binding free energy of the water molecule. This approach therefore allows the numerical assessment of whether or not a given water molecule should be targeted for displacement as part of a rational drug design strategy. PMID- 17288417 TI - Formation of a cobalt(III) imido from a cobalt(II) amido complex. Evidence for proton-coupled electron transfer. PMID- 17288419 TI - Three-dimensional porous coordination polymer functionalized with amide groups based on tridentate ligand: selective sorption and catalysis. AB - To create a functionalized porous compound, amide group is used in porous framework to produce attractive interactions with guest molecules. To avoid hydrogen-bond formation between these amide groups our strategy was to build a three-dimensional (3D) coordination network using a tridentate amide ligand as the three-connector part. From Cd(NO3)2.4H2O and a three-connector ligand with amide groups a 3D porous coordination polymer (PCP) based on octahedral Cd(II) centers, {[Cd(4-btapa)2(NO3)2].6H2O.2DMF}n (1a), was obtained (4-btapa = 1,3,5 benzene tricarboxylic acid tris[N-(4-pyridyl)amide]). The amide groups, which act as guest interaction sites, occur on the surfaces of channels with dimensions of 4.7 x 7.3 A2. X-ray powder diffraction measurements showed that the desolvated compound (1b) selectively includes guests with a concurrent flexible structural (amorphous-to-crystalline) transformation. The highly ordered amide groups in the channels play an important role in the interaction with the guest molecules, which was confirmed by thermogravimetric analysis, adsorption/desorption measurements, and X-ray crystallography. We also performed a Knoevenagel condensation reaction catalyzed by 1a to demonstrate its selective heterogeneous base catalytic properties, which depend on the sizes of the reactants. The solid catalyst 1a maintains its crystalline framework after the reaction and is easily recycled. PMID- 17288421 TI - Gd-loaded liposomes as T1, susceptibility, and CEST agents, all in one. PMID- 17288420 TI - Mechanical stabilization effect of water on a membrane-like system. AB - The penetration resistance of a prototypical model-membrane system (HS-(CH2)11-OH self-assembled monolayer (SAM) on Au(111)) to the tip of an atomic force microscope (AFM) is investigated in the presence of different solvents. The compressibility (i.e., height vs tip load) of the HS-(CH2)11-OH SAM is studied differentially, with respect to a reference structure. The reference consists of hydrophobic alkylthiol molecules (HS-(CH2)17-CH3) embedded as nanosized patches into the hydrophilic SAM by nanografting, an AFM-assisted nanolithography technique. We find that the penetration resistance of the hydrophilic SAM depends on the nature of the solvent and is much higher in the presence of water than in 2-butanol. In contrast, no solvent-dependent effect is observed in the case of hydrophobic SAMs. We argue that the mechanical resistance of the hydroxyl terminated SAM is a consequence of the structural order of the solvent-SAM interface, as suggested by our molecular dynamics simulations. The simulations show that in the presence of 2-butanol the polar head groups of the HS-(CH2)11-OH SAM, which bind only weakly to the solvent molecules, try to bind to each other, disrupting the local order at the interface. On the contrary, in the presence of water the polar head groups bind preferentially to the solvent that, in turn, mediates the release of the surface strain, leading to a more ordered interface. We suggest that the mechanical stabilization effect induced by water may be responsible for the stability of even more complex, real membrane systems. PMID- 17288422 TI - Transition of ionic liquid [bmim][PF6] from liquid to high-melting-point crystal when confined in multiwalled carbon nanotubes. PMID- 17288424 TI - Heterogeneously catalyzed living cationic polymerization of isobutyl vinyl ether using iron (III) oxide. PMID- 17288423 TI - Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced two-photon absorbing fluorescent dye aggregates for two photon photodynamic therapy. AB - We report energy-transferring organically modified silica nanoparticles for two photon photodynamic therapy. These nanoparticles co-encapsulate two-photon fluorescent dye nanoaggregates as an energy up-converting donor and a photosensitizing PDT drug as an acceptor. They combine two features: (i) aggregation-enhanced two-photon absorption and emission properties of a novel two photon dye and (ii) nanoscopic fluorescence resonance energy transfer between this nanoaggregate and a photosensitizer, 2-devinyl-2-(1 hexyloxyethyl)pyropheophorbide. Stable aqueous dispersions of the co encapsulating nanoparticles (diameter < or = 30 nm) have been prepared in the nonpolar interior of micelles by coprecipitating an organically modified silica sol with the photosensitizer and an excess amount of the two-photon dye which forms fluorescent aggregates by phase separation from the particle matrix. Using a multidisciplinary nanophotonic approach, we show: (i) indirect excitation of the photosensitizer through efficient two-photon excited intraparticle energy transfer from the dye aggregates in the intracellular environment of tumor cells and (ii) generation of singlet oxygen and in vitro cytotoxic effect in tumor cells by photosensitization under two-photon irradiation. PMID- 17288425 TI - Critical importance of length-scale dependence in implicit modeling of hydrophobic interactions. AB - The existence of length-scale dependence of hydrophobic solvation has important implications in the equilibrium of disordered, partially folded, and folded protein conformations. Neglecting this dependence, such as in popular solute surface-area based implicit solvent models with fixed surface tension coefficients, severely limits the ability to accurately model protein conformational equilibrium. We illustrate such fundamental limitations by examining the potentials of mean force of forming dimeric and trimeric nonpolar clusters and propose a new empirical model that effectively captures the context dependence of the local effective surface tension. Further optimization of the new model with other components of the implicit solvent force fields provides promise to significantly improve one's ability to simulate protein folding and conformational transitions. The existence of length-scale dependence of hydrophobic solvation has important implications in the equilibrium of disordered, partially folded, and folded protein conformations. Neglecting this dependence, such as in popular solute surface-area based implicit solvent models with fixed surface tension coefficients, severely limits the ability to accurately model protein conformational equilibrium. We illustrate such fundamental limitations by examining the potentials of mean force of forming dimeric and trimeric nonpolar clusters and propose a new empirical model that effectively captures the context dependence of the local effective surface tension. Further optimization of the new model with other components of the implicit solvent force fields provides promise to significantly improve one's ability to simulate protein folding and conformational transitions. PMID- 17288426 TI - Shapes and noncovalent interactions of oligomers: the rotational spectrum of the difluoromethane trimer. AB - The trimer of difluoromethane, (CH2F2)3, has been characterized by supersonic jet Fourier transform microwave spectroscopy. The rotational spectrum displays all types (mu(a), mu(b), and mu(c)) of transitions, showing that the adduct does not possess any element of molecular symmetry. The investigation of the three 13C species in natural abundance indicates that the three carbon atoms form a triangle where the C-C distances are 3.648(2), 3.825(8), and 3.942(6) A, respectively. The three subunits are held together by nine CH...F weak hydrogen bonds. PMID- 17288427 TI - Spirodiepoxide reaction with cuprates. PMID- 17288429 TI - Total synthesis of khafrefungin using highly stereoselective vinylogous Mukaiyama aldol reaction. AB - [structure: see text] A convergent total synthesis of khafrefungin was accomplished on the basis of (1) the highly stereoselective TiCl4-mediated vinylogous Mukaiyama aldol reaction using vinylketene silyl N,O-acetal and (2) syn-selective aldol reaction of enal 5a and ethyl ketone 6 followed by anti dehydration under Mitsunobu conditions. PMID- 17288430 TI - Conjugate addition of 2- and 4-pyridylcuprates: an expeditious asymmetric synthesis of natural (-)-evoninic acid. AB - [reaction: see text] The scope and limitations of the conjugate addition of 2- and the first 4-pyridyl Gilman homocuprates to various alpha,beta-unsaturated Michael acceptors are delineated. The conjugate addition of the cuprate of 2 bromo-3-methylpyridine to (E)-methyl crotonate then diastereoselective enolate alkylation and lipase-mediated enantioselective ester hydrolysis have enabled an efficient four-step first asymmetric synthesis of the Celastraceae sesquiterpenoid esterifying ligand (-)-(1'S,2'S)-evoninic acid. PMID- 17288431 TI - Photochromism of arylchromenes: remarkable modification of absorption properties and lifetimes of o-quinonoid intermediates. AB - [reaction: see text] A significant pi-conjugation in 6- and 7-arylchromenes manifests dramatically in the absorption properties of their photogenerated o quinonoid intermediates. This in conjunction with facile synthesis via Suzuki coupling may render a myriad of photochromic arylchromenes with wide-ranging spectrokinetic properties readily accessible. PMID- 17288432 TI - Highly enantioselective Michael addition of aromatic ketones to nitroolefins promoted by chiral bifunctional primary amine-thiourea catalysts based on saccharides. AB - [reaction: see text] A new class of thiourea catalysts have been developed which integrate saccharide and primary amine moieties into one small organic molecule. These simple catalysts are shown to be highly enantioselective for direct Michael addition of aromatic ketones to a range of nitroolefins (up to 98% ee). PMID- 17288433 TI - Acetylation of soybean lecithin and identification of components for solubility in supercritical carbon dioxide. AB - There is a growing interest to develop environmentally friendly surfactants for utilization with supercritical carbon dioxide (scCO2), which is a "green" solvent with many industrial applications. The goal of the present work was to separate the commonly used soybean lecithin into a phospholipid-rich fraction, acetylate this fraction, and then test its solubility in scCO2 to gauge its suitability as a surfactant for potential scCO2-based applications. Soybean lecithin was first purified by fractionation using acetone and ethanol and then acetylated with acetic anhydride. The acetylated lecithin was further purified by fractionation with acetone to separate the acetylated fraction from the nonacetylated fraction. High-performance liquid chromatography and electrospray ionization mass spectrometry were utilized to characterize these fractions. The various acetylated phospholipid fractions were then tested for solubility in scCO2 under various pressures and temperatures using both a cloud-point and a Fourier transform infrared apparatus. Acetylation was found to increase the solubility of the phospholipids in scCO2, and N-acetylated phosphatidylethanolamine (NAc-PE) was found to be the most soluble component of the acetylated phospholipids. PMID- 17288434 TI - Role of phospholipase A2 in the induction of drip loss in porcine muscle. AB - The role of phospholipase A2 in the induction of drip loss from pig muscle has been investigated. In samples from porcine M. longissimus dorsi, total PLA2 activity as well as mRNA and protein levels of the group VIA iPLA2 (iPLA2-VIA) increased during the initial 4 h post-mortem period. Morphological studies of porcine muscle showed that at 4 h post-mortem, gaps had formed between muscle fibers and that the sarcolemma membrane borders appeared blurred. At the same time iPLA2-VIA protein levels were increased inside muscle fibers and at the sarcolemma. iPLA2-VIA mRNA abundance in samples from different breeds of pigs with variations in drip loss revealed no clear correlation between drip loss level and iPLA2-VIA expression. Together, these data indicate that during the post-mortem period, iPLA2-VIA expression and activity is increased at the muscle fiber membranes. PLA2 activity may affect membrane permeability and consequently the progression of drip formation in porcine muscle. PMID- 17288435 TI - Flavonoids of zoysiagrass (Zoysia spp.) cultivars varying in fall armyworm (Spodoptera frugiperda) resistance. AB - Flavonoid profiles of 12 zoysiagrass (Zoysia spp.) cultivars sampled six times in 1998 were correlated to fall armyworm (Spodoptera frugiperda J. E. Smith) larval weights and survival on replicated field-grown plant material and analyzed to determine genetic and seasonal variations of flavonoids among zoysiagrass cultivars. From multiple regression analyses and correlations, flavonoid peak 10 (luteolin-glucoside) had the greatest positive association with average fall armyworm weight; however, resistance appeared to be correlated with a number of other flavonoids. The flavonoid profiles of cultivars subjected to clustering procedures showed consistent genetic variability for five of six samplings and was used to genotype 23 cultivars. The dendrogram supported the results of the FASTCLUS procedure in clustering certain genotypes such as fall armyworm resistant Cavalier and Zeon together, as well as J-36 and Meyer. Flavonoid evaluations measure genetic relatedness among cultivars and could be used for selective breeding of resistance to fall armyworm. PMID- 17288436 TI - Homogenization conditions affect the oxidative stability of fish oil enriched milk emulsions: oxidation linked to changes in protein composition at the oil water interface. AB - Fish oil was incorporated into milk under different homogenization temperatures (50 and 72 degrees C) and pressures (5, 15, and 22.5 MPa). Subsequently, the oxidative stability of the milk and changes in the protein composition of the milk fat globule membrane (MFGM) were examined. Results showed that high pressure and high temperature (72 degrees C and 22.5 MPa) resulted in less lipid oxidation, whereas low pressure and low temperature (50 degrees C and 5 MPa) resulted in faster lipid oxidation. Analysis of protein oxidation indicated that especially casein was prone to oxidation. The level of free thiol groups was increased by high temperature (72 degrees C) and with increasing pressure. Furthermore, SDS-PAGE and confocal laser scanning microscopy (CLSM) indicated that high temperature resulted in an increase in beta-lactoglobulin adsorbed at the oil-water interface. This was even more pronounced with higher pressure. Less casein seemed to be present at the oil-water interface with increasing pressure. Overall, the results indicated that a combination of more beta-lactoglobulin and less casein at the oil-water interface gave the most stable emulsions with respect to lipid oxidation. PMID- 17288437 TI - Homogenization conditions affect the oxidative stability of fish oil enriched milk emulsions: lipid oxidation. AB - In this study fish oil was incorporated into commercial homogenized milk using different homogenization temperatures and pressures. The main aim was to understand the significance of homogenization temperature and pressure on the oxidative stability of the resulting milks. Increasing homogenization temperature from 50 to 72 degrees C decreased droplet size only slightly, whereas a pressure increase from 5 to 22.5 MPa decreased droplet size significantly. Surprisingly, emulsions having small droplets, and therefore large interfacial area, were less oxidized than emulsions having bigger droplets. Emulsions with similar droplet size distributions, but resulting from different homogenization conditions, had significantly different oxidative stabilities, indicating that properties of significance to oxidation other than droplet size itself were affected by the different treatments. In general, homogenization at 72 degrees C appeared to induce protective effects against oxidation as compared to homogenization at 50 degrees C. The results thus indicated that the actual composition of the oil water interface is more important than total surface area itself. PMID- 17288438 TI - Specific detection of potentially allergenic kiwifruit in foods using polymerase chain reaction. AB - Kiwifruit (Actinidia deliciosa and Actinidia chinensis) is allergenic to sensitive patients, and, under Japanese regulations, it is one of the food items that are recommended to be declared on food labeling as much as possible. To develop PCR-based methods for the detection of trace amounts of kiwifruit in foods, two primer pairs targeting the ITS-1 region of the Actinidia spp. were designed using PCR simulation software. On the basis of the known distribution of a major kiwifruit allergen (actinidin) within the Actinidia spp., as well as of reports on clinical and immunological cross-reactivities, one of the primer pairs was designed to detect all Actinidia spp. and the other to detect commercially grown Actinidia spp. (i.e., kiwifruit, Actinidia arguta, and their interspecific hybrids) except for Actinidia polygama. The specificity of the developed methods using the designed primer pairs was verified by performing PCR experiments on 8 Actinidia spp. and 26 other plants including fruits. The methods were considered to be specific enough to yield target-size products only from the target Actinidia spp. and to detect no target-size products from nontarget species. The methods were sensitive enough to detect 5-50 fg of Actinidia spp. DNA spiked in 50 ng of salmon testis DNA used as a carrier (1-10 ppm of kiwifruit DNA) and 1700 ppm (w/w) of fresh kiwifruit puree spiked in a commercial plain yogurt (corresponding to ca. 10 ppm of kiwifruit protein). These methods would be expected to be useful in the detection of hidden kiwifruit and its related species in processed foods. PMID- 17288439 TI - Acidolysis of tristearin with selected long-chain fatty acids. AB - Five lipases, namely, Candida antarctica (Novozyme-435), Mucor miehei (Lipozyme IM), Pseudomonas sp. (PS-30), Aspergillus niger (AP-12), and Candida rugosa (AY 30), were screened for their effect on catalyzing the acidolysis of tristearin with selected long-chain fatty acids. Among the lipases tested C. antarctica lipase catalyzed the highest incorporation of oleic acid (OA, 58.2%), gamma linolenic acid (GLA, 55.9%), eicosapentaenoic acid (EPA, 81.6%), and docosahexaenoic acid (DHA, 47.7%) into tristearin. In comparison with other lipases examined, C. rugosa lipase catalyzed the highest incorporation of linoleic acid (LA, 75.8%), alpha-linolenic acid (ALA, 74.8%), and conjugated linoleic acid (CLA, 53.5%) into tristearin. Thus, these two lipases might be considered promising biocatalysts for acidolysis of tristearin with selected long chain fatty acids. EPA was better incorporated into tristearin than DHA using the fifth enzymes. LA incorporation was better than CLA. ALA was more reactive than GLA during acidolysis, except for the reaction catalyzed by Pseudomonas sp., possibly due to structural differences (location and geometry of double bonds) between the two fatty acids. In another set of experiments, a combination of equimolar quantities of unsaturated C18 fatty acids (OA + LA + CLA + GLA + ALA) was used for acidolysis of tristearin to C18 fatty acids at ratios of 1:1, 1:2, and 1:3. All lipases tested catalyzed incorporation of OA and LA into tristearin except for M. miehei, which incorportaed only OA. C. rugosa lipase better catalyzed incorporation of OA and LA into tristearin than other lipases tested, whereas the lowest incorporation was obtained using Pseudomonas sp. As the mole ratio of substrates increased from 1 to 3, incorporation of OA and LA increased except for the reaction catalyzed by A. niger and C. rugosa. All lipases tested failed to allow GLA or CLA to participate in the acidolysis reaction, and ALA was only slightly incoporated into tristearin when M. miehei was used. PMID- 17288440 TI - Characterization of topical antiinflammatory compounds in Rosmarinus officinalis L. AB - The topical antiinflammatory activity of three extracts at increasing polarity (n hexane, chloroform, and methanol) from the leaves of Rosmarinus officinalis L. (Labiatae) has been tested using the croton oil ear test in mice. Both the n hexane and the chloroform (CE-1) extracts from the leaves showed a dose-dependent activity, the last one possessing an antiinflammatory potency similar to that of indomethacin, the nonsteroidal antiinflammatory drug used as a reference drug (ID50 = 83 and 93 microg/cm2, respectively). The bioassay-oriented fractionation of CE-1 led to the identification of tritepenes, ursolic acid, oleanolic acid, and micromeric acid as the main antiinflammatory principles. Furthermore, the CE 1 extract obtained from the residue of the steam distillation of the leaves (extract A) showed the same antiinflammatory potency of CE-1, suggesting this waste product as a source of antiinflammatory products. PMID- 17288441 TI - Development of an oat-based biorefinery for the production of L(+)-lactic acid by Rhizopus oryzae and various value-added coproducts. AB - A novel oat-based biorefinery producing L(+)-lactic acid and various value-added coproducts (e.g., beta-glucan, anti-irritant solution) is proposed. Pearling is employed for sequential separation of bran-rich fractions for the extraction of value-added coproducts. Lactic acid production is achieved via fungal fermentation of Rhizopus oryzae on pearled oat flour. Maximum lactic acid concentration (51.7 g/L) and starch conversion yield (0.68 g/g) were achieved when an oat flour concentration of 116.5 g/L was used. Oxygen transfer played a significant role with respect to lactic acid production and starch conversion yield. Rhizopus oryzae produced a range of enzymes (glucoamylase, protease, phosphatase) for the hydrolysis of cereal flour macromolecules. Enzyme production during fungal fermentation has been reported. The proposed biorefining strategy could lead to significant operating cost reduction as compared to current industrial practices for lactic acid production from pure glucose achieved by bacterial fermentations. PMID- 17288442 TI - Molecular docking and three-dimensional quantitative structure-activity relationship studies on the binding modes of herbicidal 1-(substituted phenoxyacetoxy)alkylphosphonates to the E1 component of pyruvate dehydrogenase. AB - Molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies on the title compounds were performed to explore the possible inhibitory mechanism. To determine the probable binding conformations of the title phosphonate derivatives, the most potent compound 12 was chosen as a standard template and docked into the active site of PDHc E1. On the basis of the binding conformations, highly predictive 3D-QSAR models were developed with q2 values of 0.872 and 0.873 for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), respectively. The predictive abilities of these models were validated by using a set of compounds that were not included in the training set. Both the CoMFA and the CoMSIA field distributions are in good agreement with the spatial and electronic structural characteristics of the binding groove of PDHc E1 selected in this work. Mapping the 3D-QSAR models to the active site of PDHc E1 provides new insight into the protein-inhibitor interaction mechanism, which is most likely valuable and applicable for designing highly active compounds in the future. PMID- 17288443 TI - Volatile profiles of dry-cured meat products from three different Iberian x Duroc genotypes. AB - Volatile profiles of two Iberian dry-cured products, dry-cured loin and ham, from three different Iberian x Duroc genotypes, was assessed. Three groups of 10 pigs, each (5 males and 5 females) from different genotypes, were studied: GEN1 = male Iberian x female Duroc1; GEN2 = male Duroc1 x female Iberian; and GEN3 = male Duroc2 x female Iberian. The genotype Duroc1 (DU1) corresponded to pigs selected for the production of dry-cured meat products (hams, loins, and shoulders), with a high level of fattening, while the genotype Duroc2 (DU2) corresponded to animals selected for meat production. Genotype slightly affected the volatile profiles of both dry-cured meat products, although dry-cured loin from GEN3 showed higher hexanal content. Dry-cured loin showed a volatile profile very different to that found in dry-cured ham. Volatile compounds of dry-cured meat products were mainly originated by lipid and protein degradation. Most of the volatile detected in both meat products came from lipid oxidation such as acids, aldehydes, ketones, alcohols, and hydrocarbons. In addition, a high proportion of volatile compounds from the Maillard reaction was found. Branched aldehydes and some sulfur and nitrogen compounds have their origin in the amino acids degradation by the Strecker reaction, while branched alcohols and acids come from the lipid oxidation of branched aldehydes. Dry-cured ham showed a higher number and a higher level of compounds with origin in protein and lipid degradation than dry-cured loin, which agrees with the longer ripening of the hams (24 months) with respect to the loins (4 months). In dry-cured loins, apart from these compounds, seasoning mixture provides high amount of volatiles, such as terpenes (from paprika and oregano) and sulfur compounds (from garlic), which have great importance in the overall aroma of this product. PMID- 17288444 TI - Biodegradation of Cry1Ab protein from Bt transgenic rice in aerobic and flooded paddy soils. AB - Degradation of Cry1Ab protein from Bt transgenic rice was examined under both aerobic and flooded conditions in five paddy soils and in aqueous solutions. The hydrolysis rate of Cry1Ab protein in aqueous solutions was correlated inversely with the solution pH in the range of 4.0 to 8.0, and positively with the initial concentration of Cry1Ab protein. Rapid degradation of Cry1Ab protein occurred in paddy soils under aerobic conditions, with half-lives ranging from 19.6 to 41.3 d. The degradation was mostly biotic and not related to any specific soil property. Degradation of the Cry1Ab protein was significantly prolonged under flooded conditions compared with aerobic conditions, with half-lives extended to 45.9 to 141 d. These results suggest that the toxin protein, when introduced into a paddy field upon harvest, will probably undergo rapid removal after the field is drained and exposed to aerobic conditions. PMID- 17288445 TI - Extraction of RNA from fresh, frozen, and lyophilized tuber and root tissues. AB - A method for isolating transcriptionally competent RNA from fresh, frozen, and lyophilized plant storage tissues containing high levels of starch and phenolics is described. The protocol avoids the use of guanidium salts, which often lead to the formation of a viscous gel during extraction of high starch-containing tissues, and instead uses a borate-Tris buffer in combination with high concentrations of NaCl, Na2SO3, and sodium dodecyl sulfate in the extraction medium. RNA was extracted from fresh, frozen, and lyophilized tissues of potato tubers, storage roots of sweet potato, radish, and turnip, and rhizomes of ginger. The yield of RNA from potato tubers averaged 281 microg g fresh weight( 1) and 1584 microg g dry weight(-1) from frozen and lyophilized samples, respectively. A260/A230 ratios of potato RNA extracts were 2.2 or greater, indicating minimal contamination by polyphenols and carbohydrates. Similarly, A260/A280 ratios exceeded 1.9, demonstrating minimal contamination of the RNA by tuber protein. While A260/A280 ratios of extracts from the other plant species were somewhat lower than those for potato (average = 1.56 and 1.80 for fresh and lyophilized samples, respectively), A260/A230 ratios averaged more than 2.0, and the RNA extracted from fresh and lyophilized samples of all species was intact, as demonstrated by denaturing agarose-formaldehyde gel electrophoresis. The protocol yielded RNA suitable for downstream molecular applications involving reverse transcription-polymerase chain reaction from all five species. Transcriptionally competent RNA was also recovered from lyophilized potato tuber tissue stored for 6 years (ambient temperature) by a simple modification to the protocol involving extraction in cold acetone. Lyophilization can thus be used to preserve RNA in high starch- and phenolic-containing plant tissues for studies on gene expression. PMID- 17288446 TI - Synthesis of 1-piperideine-6-carboxylic acid produced by L-lysine-epsilon aminotransferase from the Streptomyces clavuligerus gene expressed in Escherichia coli. AB - The gene (lat) encoding L-lysine epsilon-aminotransferase (LAT) in Streptomyces clavuligerus was cloned and expressed in Escherichia coli. Nucleotide sequence analysis of lat predicted a single open reading frame (ORF) of 1371 bp, encoding a polypeptide of 457 amino acids with calculated molecular mass of 49.89 kDa. S. clavuligerus LAT was grouped into aminotransferase subfamily II of alpha family on the basis of sequence homology. A model system composed of the recombinant LAT in phosphate buffer was set up to study the biosynthesis of 2 acetyltetrahydropyridine. Lysine was found to be transformed to 1-piperideine-6 carboxylic acid. 2-Acetyltetrahydropyridine was characterized from the mixture of 1-piperideine-6-carboxylic acid and methylglyoxal. For the first time, we demonstrated that the L-lysine epsilon-aminotransferase is responsible for the formation of 1-piperideine-6-carboxylic acid, which may react with methylglyoxal to generate the acylated N-heterocyclic odorant 2-acetyltetrahydropyridine. PMID- 17288447 TI - Shelf-life modeling of bakery products by using oxidation indices. AB - The aim of this work was to develop a shelf-life prediction model of lipid containing bakery products. To this purpose (i) the temperature dependence of the oxidation rate of bakery products was modeled, taking into account the changes in lipid physical state; (ii) the acceptance limits were assessed by sensory analysis; and (iii) the relationship between chemical oxidation index and acceptance limit was evaluated. Results highlight that the peroxide number, the changes of which are linearly related to consumer acceptability, is a representative index of the quality depletion of biscuits during their shelf life. In addition, the evolution of peroxides can be predicted by a modified Arrhenius equation accounting for the changes in the physical state of biscuit fat. Knowledge of the relationship between peroxides and sensory acceptability together with the temperature dependence of peroxide formation allows a mathematical model to be set up to simply and quickly calculate the shelf life of biscuits. PMID- 17288448 TI - Polycyclic aromatic hydrocarbons in marine organisms from the Gulf of Naples, Tyrrhenian Sea. AB - Polycyclic aromatic hydrocarbons (PAHs) were determined by an HPLC method with fluorescence detection in bivalves (Mitylus galloprovincialis), cephalopods (Todarodes sagittatus), crustaceans (Aristeus antennatus), and fish (Mullus surmeletus, Scomber scombrus, Micromesistius poutassou, and Merluccius merluccius) caught in the Gulf of Naples (Tyrrhenian Sea, Italy). Anthracene, fluoranthene, pyrene, benz(a)anthracene, chrysene, benzo(b)fluoranthene, and benzo(k)fluoranthene were detected, at different concentrations, in all of the examined marine organisms, whereas benzo(a)pyrene, dibenz(a,h)anthracene, benzo(g,h,i)perylene, and indeno(1,2,3-cd)pyrene were found only in Mediterranean mussels. Of mussels collected in winter 71.43% exceeded the maximum residual levels (MRL) fixed for the benzo(a)pyrene in European Regulation 208/2005/EC, whereas all samples collected in summer reported values lower than this limit. In comparison to the other marine organisms, the mussels showed the highest PAH concentrations (p < 0.01). Fish showed total PAH levels lower than those of cephalopods and, in particular, European hake showed the lowest values (6.06 ng/g of fresh weight). PMID- 17288449 TI - Nondestructive determination of oil content and fatty acid composition in perilla seeds by near-infrared spectroscopy. AB - Near-infrared reflectance spectroscopy (NIRS) was used as a rapid and nondestructive method to determine the oil content and fatty acid composition in intact seeds of perilla [Perilla frutescens var. japonica (Hassk.) Hara] germplasms in Korea. A total of 397 samples (about 2 g of intact seeds) were scanned in the reflectance mode of a scanning monochromator, and the reference values for the oil content and fatty acid composition were measured by gravimetric method and gas-liquid chromatography, respectively. Calibration equations for oil and individual fatty acids were developed using modified partial least-squares regression with internal cross validation (n = 297). The equations for oil and oleic and linolenic acid had lower standard errors of cross validation (SECV), higher R2 (coefficient of determination in calibration), and higher ratio of unexplained variance divided by variance (1-VR) values than those for palmitic, stearic, and linoleic acid. Prediction of an external validation set (n = 100) showed significant correlation between reference values and NIRS estimated values based on the standard error of prediction (SEP), r2 (coefficient of determination in prediction), and the ratio of standard deviation (SD) of reference data to SEP. The models for oil content and major fatty acids, oleic and linolenic acid, had relatively higher values of SD/SEP(C) and r2 (more than 3.0 and 0.9, respectively), thereby characterizing those equations as having good quantitative information, whereas those of palmitic, stearic, and linoleic acid had lower values (below 2.0 and 0.7, respectively), unsuitable for screening purposes. The results indicated that NIRS could be used to rapidly determine oil content and fatty acid composition (oleic and linolenic acid) in perilla seeds in the breeding programs for development of high-quality perilla oil. PMID- 17288450 TI - On the effect of tetraborate ions in the generation of colored products in thermally processed glycine-carbohydrate solutions. AB - The effect of tetraborate ions on Maillard browning was investigated in a series of monosaccharide-glycine reactions in aqueous bis-tris buffer at pH 7.2. Addition of borax (sodium tetraborate) in catalytic amounts led to enhanced browning measured by absorbance at 420 nm in the order xylose > arabinose > galactose approximately = fructose > ribose > mannose > rhamnose, and the degree of browning with borax was uniformly greater than that produced by phosphate on an equimolar basis. A mechanism is proposed for borax catalysis in which monosaccharide-borate complexation shifts carbohydrate equilibria to favor open chain (carbonyl) forms, thereby enhancing the rate of the Maillard reaction. PMID- 17288451 TI - RNA-p53 interactions in vitro. AB - The tumor suppressor protein p53 is mutated in over half of human cancers. Despite 25 years of study, the complex regulation of this protein remains unclear. After serendipitously detecting RNA binding by p53 in the yeast three hybrid system (Y3H), we are exploring the specificity and function of this interaction. Electrophoretic mobility shift assays show that full-length p53 binds equally to RNAs that are strongly distinguished in the Y3H. RNA binding blocks sequence-specific DNA binding by p53. The C-terminus of p53 is necessary and sufficient for strong RNA interaction in vitro. Mouse and human C-terminal p53 peptides have different affinities for RNA, and an acetylated human p53 C terminal peptide does not bind RNA. Circular dichroism spectroscopy of p53 peptides shows that RNA binding does not induce a structural change in the p53 C terminal peptide, and C-terminal peptides do not detectably affect the structure of RNA. These results demonstrate that p53 binds RNA with little sequence specificity, RNA binding has the potential to regulate DNA binding, and RNA-p53 interactions can be regulated by acetylation of the p53 C-terminus. PMID- 17288452 TI - Sodium-independent low-affinity D-glucose transport by human sodium/D-glucose cotransporter 1: critical role of tryptophan 561. AB - Although there is no evidence of significant Na-independent glucose flux in tissues naturally expressing SGLT1, previous kinetic and biophysical studies suggest that sodium/d-glucose cotransporter 1 (hSGLT1) can facilitate sodium independent d-glucose transport and may contain more than one sugar binding site. In this work, we analyze the kinetic properties and conformational states of isolated hSGLT1 reconstituted in liposomes by transport and fluorescence studies in the absence of sodium. In the transport studies with hSGLT1, significant sodium-independent phlorizin inhibitable alpha-methyl d-glucopyranoside (alpha MDG) uptake was observed which amounted to approximately 20% of the uptake observed in the presence of a sodium gradient. The apparent affinity constant for alpha-MDG was thereby 3.4 +/- 0.5 mM, a value approximately 10-fold higher than that in the presence of sodium. In the absence of sodium, various sugars significantly decreased the intrinsic Trp fluorescence of hSGLT1 in proteoliposomes exhibiting the following sequence of affinities: alpha-MDG > d glucose approximately d-galactose > 6-deoxy-d-glucose > 2-deoxy-d-glucose > d allose. Furthermore, significant protection effects of d-glucose or phlorizin against potassium iodide, acrylamide, or trichloroethanol quenching were observed. To locate the Trps involved in this reaction, we generated mutants in which all Trps were sequentially substituted with Phe. None of the replacements significantly affected sodium-dependent uptake. Uptake in the absence of sodium and typical fluorescence changes depended, however, on the presence of Trp at position 561. This Trp residue is conserved in all known SGLT1 forms (except Vibrio parahaemolyticus SGLT) and all SGLT isoforms in humans (except hSGLT3). If all these data are taken into consideration, it seems that Trp-561 in hSGLT1 forms part of a low-affinity sodium-independent binding and/or translocation site for d-glucose. The rate of sodium-independent translocation via hSGLT1 seems, however, to be tightly regulated in the intact cell by yet unknown factors. PMID- 17288453 TI - A structurally altered D,L-amino acid TCRalpha transmembrane peptide interacts with the TCRalpha and inhibits T-cell activation in vitro and in an animal model. AB - Protein-protein interactions in the membrane are pivotal for the cellular response to receptor-sensed stimuli. Recently, it has been demonstrated that an all-d-amino acids analogue of the TCRalpha transmembrane peptide (CP) is recruited to the TCR complex and inhibits T-cell activation in vitro and in vivo, similarly to the wild-type CP peptide. Here we investigated the relative contributions of the secondary structure of CP compared to its side chains in the association of CP with the TCR. We disrupted the secondary structure of CP by replacing two positive residues, needed for the interaction of CP with the TCR complex, by their d-enantiomers (2D-CP). Structure disruption was demonstrated by CD and FTIR spectroscopy, and molecular dynamics simulation in a bilayer environment. In vitro, 2D-CP colocalized with the TCR (visualized with confocal microscopy), immunoprecipitated with TCR but not MHC I, and inhibited T-cell activation. The peptide was effective also in vivo: it inhibited adjuvant arthritis in rats and delayed type hypersensitivity in BALB/c mice. Moreover, 2D CP manifested greater immunosuppressive activity than wild-type CP, both in vivo and in vitro, which can be attributed to the greater solubility and resistance to degradation of 2D-CP. In molecular terms, these findings suggest that, under certain conditions, protein-protein interactions within the membrane might be more dependent on side chain interactions than on a specific secondary structure. The new altered secondary structure probably determines how the Lys and the Arg are positioned with respect to each other, so they can interact with the TM domain of the receptor. In clinical terms, the increased solubility and resistance to degradation of d-stereoisomers might be exploited in the targeted inactivation of pathogenic signaling pathways such as those arising from TCR triggered activation of T-cells in immune-mediated disorders. PMID- 17288454 TI - Lymphoblasts of women with BRCA1 mutations are deficient in cellular repair of 8,5'-Cyclopurine-2'-deoxynucleosides and 8-hydroxy-2'-deoxyguanosine. AB - Mutations in breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 predispose women to a high risk of these cancers. Here, we show that lymphoblasts of women with BRCA1 mutations who had been diagnosed with breast cancer are deficient in the repair of some products of oxidative DNA damage, namely, 8 hydroxy-2'-deoxyguanosine and 8,5'-cyclopurine-2'-deoxynucleosides. Cultured lymphoblasts from 10 individuals with BRCA1 mutations and those from 5 control individuals were exposed to 5 Gy of ionizing radiation to induce oxidative DNA damage and then allowed to repair this damage. DNA samples isolated from these cells were analyzed by liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry to measure 8-hydroxy-2'-deoxyguanosine, (5'-S) 8,5'-cyclo-2'-deoxyadenosine, (5'-R)-8,5'-cyclo-2'-deoxyguanosine, and (5'-S) 8,5'-cyclo-2'-deoxyguanosine. After irradiation and a subsequent period of repair, no significant accumulation of these lesions was observed in the DNA from control cells. In contrast, cells with BRCA1 mutations accumulated statistically significant levels of these lesions in their DNA, providing evidence of a deficiency in DNA repair. In addition, a commonly used breast tumor cell line exhibited the same effect when compared to a relevant control cell line. The data suggest that BRCA1 plays a role in cellular repair of oxidatively induced DNA lesions. The failure of cells with BRCA1 mutations to repair 8,5'-cyclopurine-2' deoxynucleosides indicates the involvement of BRCA1 in nucleotide-excision repair of oxidative DNA damage. This work suggest that accumulation of these lesions may lead to a high rate of mutations and to deleterious changes in gene expression, increasing breast cancer risk and contributing to breast carcinogenesis. PMID- 17288455 TI - Glassy dynamics in the folding landscape of cytochrome c detected by laser photolysis. AB - Ferrocytochrome c liganded with CO refolds to a nativelike compact state, called the M state, where the non-native Fe2+-CO contact persists. The M state resembles the generic molten globule-like states and can be driven to the native state by pulsed laser photolysis of the CO ligand. The microsecond kinetics measured all across the guanidine hydrochloride unfolding transition of the protein produce a chevron plot with accentuated rollover in the folding limb, suggesting a glass transition of M en route to N. The rate of exit of the folding structure from the kinetic trap(s) limits the overall rate of folding of M to N. Sulfate-induced deceleration of the observed folding rate suggests that the folding structure indeed is transiently frozen in glassy traps. The results connect the post transition features of the funnel paradigm. PMID- 17288456 TI - Modulation of FXYD interaction with Na,K-ATPase by anionic phospholipids and protein kinase phosphorylation. AB - FXYD10 is a 74 amino acid small protein which regulates the activity of shark Na,K-ATPase. The lipid dependence of this regulatory interaction of FXYD10 with shark Na,K-ATPase was investigated using reconstitution into DOPC/cholesterol liposomes with or without the replacement of 20 mol % DOPC with anionic phospholipids. Specifically, the effects of the cytoplasmic domain of FXYD10, which contains the phosphorylation sites for protein kinases, on the kinetics of the Na,K-ATPase reaction were investigated by a comparison of the reconstituted native enzyme and the enzyme where 23 C-terminal amino acids of FXYD10 had been cleaved by mild, controlled trypsin treatment. Several kinetic properties of the Na,K-ATPase reaction cycle as well as the FXYD-regulation of Na,K-ATPase activity were found to be affected by acidic phospholipids like PI, PS, and PG. This takes into consideration the Na+ and K+ activation, the K+-deocclusion reaction, and the poise of the E1/E2 conformational equilibrium, whereas the ATP activation was unchanged. Anionic phospholipids increased the intermolecular cross-linking between the FXYD10 C-terminus (Cys74) and the Cys254 in the Na,K-ATPase A-domain. However, neither in the presence nor in the absence of anionic phospholipids did protein kinase phosphorylation of native FXYD10, which relieves the inhibition, affect such cross-linking. Together, this seems to indicate that phosphorylation involves only modest structural rearrangements between the cytoplasmic domain of FXYD10 and the Na,K-ATPase A-domain. PMID- 17288457 TI - An EPR spin label study of the quinol oxidase, E. coli cytochrome bo3: a search for redox induced conformational changes. AB - A search for conformational changes at the cytosolic entrance to the proton channels of the heme-copper quinol oxidase (QO), cytochrome bo3, E. coli, has been carried out using site directed nitroxide spin labeling (SDSL) of cysteine residues. These were positioned at R134 and R309, on loops that link helices II and III and VI and VII at the entrances to the D and K proton channels, respectively. The motional characteristics of both labels have been determined using X- and W-band EPR spectroscopy at room temperature in selected redox levels in the reaction sequence of QO with oxygen, namely, the mixed valence carbon monoxide form (COMV), the oxidized (O) and super-oxidized (PM) states. The O to PM step is accompanied by the uptake of protons through the K pathway. We find no evidence for changes in the motional characteristics of either label that are expected to be associated with helical motions at the entrances to the channels. Because kinetic studies of mutants show that the redox gating of protons occurs deep within the D channel close to the heme-copper site, the present study implies that no motion is transmitted to the ends of the helices. PMID- 17288458 TI - Mutations within the C-terminus of the gamma subunit of the photosynthetic F1 ATPase activate MgATP hydrolysis and attenuate the stimulatory oxyanion effect. AB - Two highly conserved amino acid residues near the C-terminus within the gamma subunit of the mitochondrial ATP synthase form a "catch" with an anionic loop on one of the three beta subunits within the catalytic alphabeta hexamer of the F1 segment [Abrahams, J. P., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628]. Forming the catch is considered to be an essential step in cooperative nucleotide binding leading to gamma subunit rotation. The analogous residues, Arg304 and Gln305, in the chloroplast F1 gamma subunit were changed to leucine and alanine, respectively. Each mutant gamma was assembled together with alpha and beta subunits from Rhodospirillum rubrum F1 into a hybrid photosynthetic F1 that carries out both MgATPase and CaATPase activities and ATP dependent gamma rotation [Tucker, W. C., Schwarcz, A., Levine, T., Du, Z., Gromet Elhanan, Z., Richter, M. L. and Haran, G. (2004) J. Biol. Chem. 279, 47415 47418]. Surprisingly, changing Arg304 to leucine resulted in a more than 2-fold increase in the kcat for MgATP hydrolysis. In contrast, changing Gln305 to alanine had little effect on the kcat but completely abolished the well-known stimulatory effect of the oxyanion sulfite on MgATP hydrolysis. The MgATPase activities of combined mutants with both residues substituted were strongly inhibited, whereas the CaATPase activities were inhibited, but to a lesser extent. The results indicate that the C-terminus of the photosynthetic F1 gamma subunit, like its mitochondrial counterpart, forms a catch with the alpha and beta subunits that modulates the nucleotide binding properties of the catalytic site(s). The catch is likely to be part of an activation mechanism, overcoming inhibition by free mg2+ ions, but is not essential for cooperative nucleotide exchange. PMID- 17288460 TI - Generation of improved gas linear velocities in a comprehensive two-dimensional gas chromatography system. AB - A comprehensive two-dimensional gas chromatography (GC x GC) system (for convenience defined as "split flow" GC x GC), which may be operated at improved gas linear velocities in both dimensions, has been developed. The setup is formed of an apolar 30 m x 0.25 mm i.d. column connected, by means of a Y press fit, to a detector-linked 1 m x 0.1 mm i.d. polar analytical column, which passes through the (cryogenic) modulator, and to a 0.3 m x 0.1 mm i.d. retention gap, which is connected to a manually operated split valve. The latter enables the regulation of gas flows through the second analytical column [e.g., 60:40 (FID) ratio, 50:50 ratio, 40:60 (FID) ratio, etc.], in order to generate the most appropriate gas linear velocity, which is related to each specific analysis. In the pre-sent investigation, two sets of traditional and split flow GC x GC analyses were carried out on a cod liver oil fatty acid methyl ester sample by using the same temperature programs [180-250 degrees C at (a) 3 degrees C/min and at (b) 1.3 degrees C/min] and at an average first-dimension linear velocity of approximately 35.0 cm/s; thus, primary column retention times (and therefore elution temperatures) were essentially maintained. The second-dimension linear velocity was calculated to be approximately 333 cm/s in the traditional applications, while it was split valve-regulated until the most appropriate values [(a) approximately 213 cm/s; (b) approximately 264 cm/s] were attained in the alternative applications. Substantial improvements were observed and measured in the chromatography along the y-axis, while the contour plot chemical class structure was maintained. PMID- 17288461 TI - Discrimination and evaluation of the effects of uncompensated resistance and slow electrode kinetics from the higher harmonic components of a fourier transformed large-amplitude alternating current voltammogram. AB - The influence of uncompensated resistance (also called the IRu effect, where I is current and Ru is uncompensated resistance) and slow electrode kinetics have been assessed for the dc and first five ac harmonics derived from Fourier transformed large-amplitude ac voltammetry. Resistance and rate constant conditions emphasized correspond to those where separation of effects attributable to either parameter is essentially impossible under conditions of dc cyclic voltammetry. Results derived from simulations and experiments demonstrate that it is relatively easy to discriminate and quantify contributions from these two effects over a wide range of values using the fourth and fifth harmonic ac components derived from single large-amplitude ac voltammetric measurement. Furthermore, these ac components also are essentially devoid of background charging current. Concepts developed initially from simulations are confirmed by experimental studies on the following: (a) the oxidation of ferrocene, in moderately resistive CH3CN and highly resistive CH2Cl2 (represents examples of IRu effect on a reversible electron-transfer process); (b) the reduction of a low 0.2 mM concentration of [Fe(CN)6]3- in the highly conductive 3 M KCl electrolyte media (case of slow kinetics with negligible IRu effect); (c) and reduction of a high 10 mM concentration of [Fe(CN)6]3- in less conductive aqueous 0.5 M KCl electrolyte media (example where the simultaneous effects of both IRu and slow kinetics need to be resolved). PMID- 17288462 TI - Direct electrochemical and spectroscopic assessment of heme integrity in multiphoton photo-cross-linked cytochrome C structures. AB - Multiphoton excitation (MPE) lithography offers an effective, biocompatible technique by which three-dimensional architectures comprised of proteins, enzymes, and other relevant materials may be fabricated for use in biological studies involving cellular signal transduction and neuronal networking. We present a series of studies designed to investigate the integrity of cytochrome c (cyt c) photo-cross-linked via MPE. Specifically, we have used electrochemical methods and surface-enhanced Raman spectroscopy (SERS) to determine whether photo cross-linked cyt c retains its well-characterized Fe(II/III) heme redox activity. Cyt c is observed to retain its native FeII/III electron-transfer properties, as the apparent electron-transfer rate constant, k0ET, for cyt c photo-cross-linked onto an indium-doped tin oxide (ITO) substrate was 8.4 +/- 0.2 s-1, on the same order of magnitude as literature values though somewhat slower than other immobilized cyt c studies, most likely due to unoptimized entrapment in the photo cross-linked matrix. SERS data reveals peaks corresponding to vibrational modes of an intact porphyrin ring with the Fe center intact. Cyt c has also been shown to demonstrate peroxidase-like activity, and we have evaluated the turnover rate of H2O2 at photo-cross-linked matrices relative to that at adsorbed monolayers of cyt c on glass substrates. The photo-cross-linked cyt c samples demonstrate apparent Michaelis-Menten parameters of Vm = 0.34 fmol/s and kcat/Km on the order of 104 s-1 M-1, in agreement with previously published results for aqueous cyt c. Fluorescence data obtained for mediated H2O2 turnover also indicated enzymatic activity specifically at photo-cross-linked cyt c structures. PMID- 17288463 TI - Comparison of atmospheric pressure photoionization and atmospheric pressure chemical ionization for normal-phase LC/MS chiral analysis of pharmaceuticals. AB - In this work, we compared APPI and APCI for normal-phase LC/MS chiral analysis of five pharmaceuticals. Performance was compared both by FIA and by on-column analysis using a ChiralPak AD-H column under optimized conditions. By comparison, APPI generated more reproducible signals and was less susceptible to ion suppression than APCI. APPI generated higher peak area and lower baseline noise, and therefore much higher S/N ratios. APPI sensitivity (i.e., S/N ratio) was approximately 2-130 times higher than APCI by FIA and was approximately 2.6-530 times higher than APCI by on-column analysis depending on specific compounds. The better APPI sensitivity as compared to APCI was more dramatic by on-column analysis than by FIA. APCI sensitivity was degraded by ion suppression caused by LC column bleeding components and by elevated APCI baseline noise relative to APPI. On-column APPI LODs (at S/N = 3) were 83, 16, 17, 95, and 7 pg for enantiomer #1, and 104, 23, 19, 122, and 17 pg for enantiomer #2 for benzoin, naringenin, mianserin, mephenesin, and diperodon, respectively, on a Waters ZQ. APPI offers no concern of explosion hazard relative to APCI corona needle discharge or ESI high voltage discharge when flammable solvents (e.g., hexane) are used as mobile phases. Whether APPI dopants are required depends on the IP(s) of mobile-phase solvent(s) and solvent complexes, and photon energies of VUV lamps. Dopant was not necessary for hexane-based mobile phases due to their self doping effects. Dopants did enhance Kr lamp APPI sensitivity when MeOH was used as the mobile phase. However, dopants became unnecessary for the MeOH mobile phase when the Ar lamp was used. PMID- 17288464 TI - Signal response of coexisting protein conformers in electrospray mass spectrometry. AB - Electrospray ionization mass spectrometry (ESI-MS) is a commonly used tool for characterizing conformational changes of proteins in solution. Different conformations can be distinguished on the basis of their ESI charge state distributions. ESI-MS studies carried out under semidenaturing conditions result in bi- or multimodal distributions that reflect the presence of coexisting conformers. This study explores whether the concentration ratios of these species in solution are reflected in the measured ion intensities. Experiments on two model proteins, lysozyme and myoglobin, reveal that non-native polypeptide chains tend to result in a much stronger signal response than natively folded species. The measured ion intensity ratios can differ from the actual concentration ratios by as much as 2 orders of magnitude. It is proposed that the higher ionization efficiency of unfolded proteins is due to their partially hydrophobic character, which results in a larger surface activity and facilitates protein transfer into ion-producing progeny droplets. Conversely, natively folded proteins have a lower affinity for the air/liquid interface, such that ionization of these conformers is suppressed. The extent of ion suppression is strongly dependent on the experimental conditions such as flow rate and protein concentration, which determine if ESI occurs in a charge deficient or a charge surplus regime. These aspects should be taken into account for the design of ESI-MS-based protein folding experiments and for studies that use ion intensity ratios for the determination of protein-ligand binding affinities. PMID- 17288465 TI - Determination of technetium and its speciation by surface-enhanced Raman spectroscopy. AB - Technetium-99 (Tc) is an important radionuclide of concern, and there is a great need for its detection and speciation analysis in the environment. For the first time, we report that surface-enhanced Raman spectroscopy (SERS) is capable of detecting an inorganic radioactive anion, pertechnetate (TcO4-), at approximately 10(-7) M concentration levels. The technique also allows the detection of various species of Tc such as oxidized Tc(VII) and reduced and possibly complexed Tc(IV) species by use of gold nanoparticles as a SERS substrate. The primary Raman scattering band of Tc(VII) occurs at about 904 cm-1, whereas reduced Tc(IV) and its humic and ethylenediaminetetraacetic acid (EDTA) complexes show scattering bands at about 866 and 870 cm-1, respectively. Results also indicate that Tc(IV) humic complexes are unstable and reoxidize to TcO4- upon exposure to oxygen. This study demonstrates that SERS could potentially offer a new tool and opportunity in studying Tc and its speciation and interactions in the environment at low concentrations. PMID- 17288466 TI - Collection and expansion of single cells and colonies released from a micropallet array. AB - The ability to selectively grow out individual cells possessing unique characteristics from within a mixed population is of widespread importance for biomedical investigations. Generation of genetically engineered cell lines, transformation studies, cell-based assays, and stem cell studies are examples where single-cell cloning is of immense value. The vast majority of mammalian cells grow adherent to a surface; therefore, positive selection followed by cloning of cells while the cells remain adherent to their growth surface is an important goal. We recently demonstrated a microfabricated cell array combined with laser-based release of individual array elements for positive selection of single cells. In the current work, a strategy to collect single cells for clonal expansion is described. The system enabled cloning of individual cells with 80 90% efficiency. Single cells were selected and cloned from small populations of fewer than 10,000 cells. Strategies used by cells to migrate from the pallets to form colonies on the surface of the collection device were examined. Implementation of encoded array elements made it possible to follow specific cells throughout the selection, collection, and cloning procedure. Thus, a particular cell can be identified by any number of imaging techniques, isolated, and clonally expanded to generate a homogeneous cell line or a pure sample for genetic or biochemical analysis. PMID- 17288467 TI - Colloidal graphite-assisted laser desorption/ionization mass spectrometry and MSn of small molecules. 1. Imaging of cerebrosides directly from rat brain tissue. AB - Graphite-assisted laser desorption/ionization (GALDI) mass spectrometry (MS) was investigated for analysis of cerebrosides in a complex total brain lipid extract. Conventional MALDI MS and GALDI MS were compared regarding lipid analysis by using high-vacuum (HV, <10-6 Torr) LDI time-of-flight mass spectrometry and intermediate-pressure (IP, 0.17 Torr) linear ion trap mass spectrometry. Cerebrosides were not detected or detected with low sensitivity in MALDI MS because of other dominant phospholipids. By using GALDI, cerebrosides were detected as intense mass peaks without prior separation from other lipid species while mass peaks corresponding to phosphatidylcholines (PCs) were weak. The signal increase for cerebrosides and the signal decrease for PCs in GALDI MS were more significant in HV than in IP. MSn experiments of precursor ions corresponding to cerebrosides and PCs in brain lipid extract were performed to identify the detected species and distinguish isobaric ions. Twenty-two cerebroside species were detected by GALDI whereas eight cerebroside species were detected by MALDI. Sulfatides in brain lipid extract were also easily detected by GALDI MS in the negative ion mode. By forming a colloidal graphite thin film on rat brain tissue, direct lipid profiling by imaging mass spectrometry (IMS) was performed. Chemically selective images for cerebrosides and sulfatides were successfully obtained. Imaging tandem mass spectrometry (IMS/MS) was performed to generate images of specific product ions from isobaric species. PMID- 17288468 TI - Automated process for improved uniformity and versatility of layer-by-layer deposition. AB - The recently developed practice of spraying polyelectrolyte solutions onto a substrate in order to construct thin films via the layer-by-layer technique has been further investigated and extended. Here we describe a fully automated system capable of depositing thin polymer films from atomized mists of solutions containing species of complementary functionality. Film growth is shown to be similar to that in conventional "dipped" LbL assembly, whereas the reported technology allows us to realize 25-fold decreases in process times. Furthermore, complete automation removes human interaction and the possibility of operator induced nonuniformities. We extend the versatility of the spray LbL technology by depositing both weak and strong polyelectrolyte films, hydrogen-bonded films, and dendritic compounds and nanoparticles, broadening its range of future applications. Finally, the technology is used to uniformly coat an otherwise hydrophobic substrate from aqueous solutions. ESEM images indicate that the atomization process produces a conformal coating of individual nanofibers within the substrate, dramatically changing the hydrophilicity of the macroscopic surface. Such an automated system is easily converted to an array of nozzle banks and could find application in the rapid, uniform coating of large areas of textile materials. PMID- 17288469 TI - Application of fluorescence correlation spectroscopy to the measurement of local temperature in solutions under optical trapping condition. AB - Fluorescence correlation spectroscopy (FCS) was applied to the quantitative evaluation of the local heating in small domains <1 microm in solutions under the laser trapping condition in the presence of a near-infrared (NIR) laser beam at 1064 nm. On the basis of the translational diffusion coefficient of fluorescent molecules obtained by FCS, the relationship between temperature rise and the incident NIR laser power, DeltaT/DeltaP, were determined to be 62 +/- 6, 49 +/- 7, and 23 +/- 1 deg K/W in ethylene glycol, ethanol, and water, respectively, while no remarkable temperature increase was observed for deuterated water. The value of DeltaT/DeltaP linearly increased as a function of alpha/lambda (alpha is the extinction coefficient of solvent at the wavelength and lambda is the thermal conductivity of the medium). The validity and the applicability of the present method for the measurement of the local temperature increase were discussed by comparing the present results with previous ones by other various methods. PMID- 17288470 TI - Broadband dielectric study of dynamics of polymer and solvent in poly(vinyl pyrrolidone)/normal alcohol mixtures. AB - Broadband dielectric measurements of poly(vinyl pyrrolidone) (PVP)-monohydroxyl alcohol mixtures of various normal alcohols with the number of carbon atoms per molecule ranging from 1 to 9 were made in the frequency range of 20 Hz to 20 GHz at 25 degrees C. Two relaxation processes due to the reorientation of dipoles on the PVP and alcohol molecules were observed. The relaxation process at frequencies higher than 100 MHz is the primary process of alcohols, and that at frequencies lower than 10 MHz is attributed to the local chain motion of PVP. For mixtures of alcohol molecules that are smaller than propanol, the relaxation time of the alcohol increases with increasing PVP concentration, whereas for mixtures of alcohol molecules larger than butanol, the relaxation time of the alcohol decreases with increasing PVP concentration. The increase in the density of hydrogen-bonding sites upon the addition of PVP reduces the relaxation time of alcohol in the mixture, and vice versa. The relaxation time of the local chain motion of PVP increases with PVP concentration and solvent viscosity. Different time scales of the molecular motions of polymer and solvent coexist in homogeneous mixtures with hydrogen-bonded polar solvent and polymer. PMID- 17288471 TI - New aspects of the low-concentrated aniline polymerization in the solution and in SiC nanocrystals dispersion. AB - Results of the simultaneous in-situ UV-vis and open-circuit potential (OCP) monitoring of the low-concentrated aniline (An) polymerization in the presence of camphorsulfonic acid (CSA) suggested that during the induction period (IP) step a transition state formed, which probably included anilinium cation and the oxidant anion, antecedent to a propagation step. No aniline oligomers were registered at this stage but they appeared at the beginning of the propagation step under the investigation conditions. The moments of formation of insoluble pernigraniline phase and appearance of emeraldine units in the growing pernigraniline chains were ascertained by the comparison of kinetic and OCP profiles of the polymerization process both in the solution and in SiC dispersion water mediums. It is deduced that pernigraniline reduction by aniline molecules begins earlier than it is generally accepted (i.e., earlier than OCP maximum is reached) and probably in parallel to a continuing appearance of pernigraniline units even in the same chains that undergo the reduction. It was found that an addition of the SiC dispersion phase into the polymerization mixture accelerates differently all stages of the aniline polymerization. Finally, this polymerization process leads to the formation of polyaniline (PANI)-CSA shell with thickness in the range from 0.5 nm to a few nm at the SiC nanocrystals surface. PMID- 17288472 TI - Model of fluorescence intermittency in single enzymes. AB - The intermittent emission of fluorescent light from single enzymes, quantum dots, and other nanoscale systems is often characterized by statistical correlations in the emitted signal. A one-dimensional model of such correlations in enzymes, based on a model of protein conformational fluctuations developed by Kou and Xie (Phys. Rev. Lett. 2004, 93, 180603), is formulated in the present paper in terms of the dynamics of a particle moving stochastically between "on" and "off" states under the action of fractional Gaussian noise. The model yields predictions for the short and long time behavior of the following quantities: the time correlation function, C(t), of the fluctuations of the signal intensity, the distribution, f(t), of time intervals between intensity fluctuations, and the Mandel parameter, Q(t), describing the extent of bunching or anti-bunching in the signal. At short times, C(t) and f(t) are found to decay exponentially, while, at long times, they are found to decay as power laws, the exponents being functions solely of the nature of the temporal correlations in the noise. The results are in good qualitative agreement with results from single-molecule experiments on fluorescence intermittency in the enzyme cholesterol oxidase carried out by Xie and co-workers (Science 1998, 282, 1877). The Mandel parameter, Q(t), for this model is positive at short and long times, indicating super-Poisson statistics in these limits, consistent with bunching of the fluorescent signal. PMID- 17288473 TI - Liquid crystal properties of the n-alkyl-cyanobiphenyl series from atomistic simulations with ab initio derived force fields. AB - Lengthy molecular dynamics (MD) simulations were performed at constant atmospheric pressure and different temperatures for the series of the 4-n-alkyl 4'-cyanobiphenyls (nCB) with n = 6, 7, and 8. The accurate atomistic force field (Bizzarri, M.; Cacelli, I.; Prampolini, G; Tani, A. J. Phys. Chem. A 2004, 108, 10336), successfully employed to reproduce thermodynamic and transport properties of the 5CB molecule, has here been extended to higher homologues. Nematic and isotropic phases were found for all members of the series, and also, a smectic phase was (tentatively) identified for 8CB at 1 atm and 300 K. Transition temperatures reproduce the experimental values within +/-10 K. Also, structural properties as second and fourth rank orientational order parameters are in good agreement with the corresponding experimental quantities. This means that the well-known odd-even effect, observed for many properties along the nCB series, is well reproduced, despite the narrow range of oscillations, e.g., in clearing temperatures. A detailed analysis of the correlation between molecular properties and odd-even effects is presented. PMID- 17288475 TI - Coarse-grained molecular dynamics modeling of associating fluids: thermodynamics, liquid structure, and dynamics in the limit of zero association strength. AB - A continuous coarse-grained potential model for associating fluids, consisting of an off-center specific site bonded with a harmonic potential to a center particle, has been developed and used in canonical molecular dynamics simulations. The thermodynamic, structural, and dynamic properties of the limiting nonassociating reference coarse-grained fluid are investigated as functions of the mass distribution and bond strength between center and site particles. It is theoretically shown and confirmed by simulation that in this limit variations in these potential parameters do not alter the equation of state of the reference coarse-grained fluid but that they have profound influences on both the translational and the rotational dynamics. From the simulation results we arrive at some guidelines that should be kept in mind in the selection of appropriate values for the model parameters. This work provides the precursory knowledge for the study of coarse-grained associating fluids using the conventional molecular dynamics method. PMID- 17288474 TI - Effect of coenzyme Q(10) incorporation on the characteristics of nanoliposomes. AB - Coenzyme Q(10) (CoQ(10)) is incorporated in nanoliposomes composed of egg yolk phospholipid, cholesterol, and Tween 80. Atomic force microscopy, performed to characterize vesicle surface topology, shows some visible influence of CoQ(10) on the nanoliposomal structure. CoQ(10) incorporation can suppress the increase of the z-average diameter of nanoliposomes during storage for 8 months at 4 degrees C. The liposomal lipid peroxidation caused by Fe(III)/ascorbate is also significantly inhibited. Perturbation of acyl chain motion of lipids due to the presence of CoQ(10) in the bilayer is examined by fluorescence probe diphenyl hexatriene and Raman spectroscopy. Fluorescence probe studies indicate that CoQ(10) incorporation results in the microviscosity increase of nanoliposomes. The steric structure of nanoliposomes reflected by Raman spectroscopy changes obviously and shows CoQ(10) content dependency. The order parameters for the lateral interaction between chains increase. The trans conformation decrease and the gauche conformation increase as the weight contents of CoQ(10) incorporation are at 1%, 5%, 10%, and 32.5%. However, the order parameters for the longitudinal interaction in chains was higher than that of pure nanoliposomes as the weight content of CoQ(10) is at 25%. Results suggest that CoQ(10)might intercalate between lipid molecules and perturb the bilayer structure. PMID- 17288476 TI - A molecular dynamics study of a nafion polyelectrolyte membrane and the aqueous phase structure for proton transport. AB - A molecular dynamics simulation study of hydrated Nafion at water contents ranging from 5 to 20 wt % was performed to examine the structure and dynamics of the hydrated polyelectrolyte system. The simulations show that the system forms segregated hydrophobic regions consisting primarily of the polymer backbone and hydrophilic regions with an inhomogeneous water distribution. We find that the water clustering strongly depends on the water content. At low water content, only isolated small water clusters are formed. As the water content increases, it becomes increasingly possible that a predominant majority of water molecules form a single cluster, suggesting that the hydrophilic regions become connected. We characterize the atomic structures formed within the system by various atomic pair correlation functions. The water structure factor shows a peak at q values corresponding to an intercluster distance about 2.5 nm and greater. With increasing water content, the distance moves to larger values, consistent with findings from scattering experiments. We find that the degree of solvation of hydronium ions by water molecules is a strong function of water content. At 5 wt %, a majority of the hydronium ions are hydrated by no more than two water molecules, prohibiting structural diffusion. As water content increases, the hydronium ions continue to become increasingly hydrated, resulting in structures capable of forming eigen ions, a necessary step in structural diffusion. Addressing the experimentally observed fact that conductivity in these membranes abruptly drops near 5 wt %, we find that both the local structure of the poorly hydrated hydronium ions and the disconnected nature of the global morphology of the water nanonetwork at low water content should contribute to poor conductivity. PMID- 17288477 TI - Adaptive partitioning in combined quantum mechanical and molecular mechanical calculations of potential energy functions for multiscale simulations. AB - In many applications of multilevel/multiscale methods, an active zone must be modeled by a high-level electronic structure method, while a larger environmental zone can be safely modeled by a lower-level electronic structure method, molecular mechanics, or an analytic potential energy function. In some cases though, the active zone must be redefined as a function of simulation time. Examples include a reactive moiety diffusing through a liquid or solid, a dislocation propagating through a material, or solvent molecules in a second coordination sphere (which is environmental) exchanging with solvent molecules in an active first coordination shell. In this article, we present a procedure for combining the levels smoothly and efficiently in such systems in which atoms or groups of atoms move between high-level and low-level zones. The method dynamically partitions the system into the high-level and low-level zones and, unlike previous algorithms, removes all discontinuities in the potential energy and force whenever atoms or groups of atoms cross boundaries and change zones. The new adaptive partitioning (AP) method is compared to Rode's "hot spot" method and Morokuma's "ONIOM-XS" method that were designed for multilevel molecular dynamics (MD) simulations. MD simulations in the microcanonical ensemble show that the AP method conserves both total energy and momentum, while the ONIOM-XS method fails to conserve total energy and the hot spot method fails to conserve both total energy and momentum. Two versions of the AP method are presented, one scaling as O(2N) and one with linear scaling in N, where N is the number of groups in a buffer zone separating the active high-level zone from the environmental low-level zone. The AP method is also extended to systems with multiple high-level zones to allow, for example, the study of ions and counterions in solution using the multilevel approach. PMID- 17288478 TI - Septocylindrins A and B: peptaibols produced by the terrestrial fungus Septocylindrium sp. LL-Z1518. AB - Two new peptaibols, septocylindrin A (1) and septocylindrin B (2), related to the well-studied membrane-channel-forming peptaibol alamethicin, were obtained from a terrestrial isolate of the fungus Septocylindrium sp. Both 1 and 2 are linear 19 amino acid peptides with a modified phenylalanine C-terminus. Analysis of the HRMS data indicated that they differ only in the 18th residue, where 1 contains Glu and 2 contains Gln. The structures of these two peptaibols were determined by extensive NMR and HRMS analysis. The absolute configurations of amino acids present in 1 were determined using Marfey's methodology. Both compounds were isolated through bioassay-guided fractionation and exhibited significant antibacterial and antifungal activity. PMID- 17288479 TI - Conformational and configurational dynamics of a highly fluorinated hydrazone. AB - The relative populations of two rotamers in the hydrazone of 2H-perfluoro-2 methyl-3-pentanone can be altered from one extreme to the other by increasing the Lewis basicity of the solvent, and the equilibrium E/Z ratio grows correspondingly. Both trends reflect an increase in the effective size of the amino group as a result of hydrogen bonding. The rate of E/Z interconversion is insensitive to the choice of solvent, consistent with the conclusion that the isomerization occurs via N-inversion and not C=N bond rotation. PMID- 17288480 TI - Synthesis, mechanism of formation, and dynamics of a highly fluorinated methylenecyclobutene. AB - Treatment of the hydrazone of 2H-perfluoro-2-methyl-3-pentanone with triethylamine at elevated temperatures yields a methylenecyclobutene via degradation to an acetylene followed by dimerization. The dimerization occurs even at -78 degrees C, and details of the reaction pathway have been elucidated. Both the acidity and the conformational dynamics of the methylenecyclobutene are influenced by buttressing effects in this crowded molecule. PMID- 17288481 TI - Catalytic [2+2+2] and thermal [4+2] cycloaddition of 1,2 bis(arylpropiolyl)benzenes. AB - We have determined that a cationic rhodium(I)/Segphos complex catalyzes an enantio- and diastereoselective intermolecular [2+2+2] cycloaddition of 1,2 bis(arylpropiolyl)benzenes with various monoalkynes at room temperature to give axially chiral 1,4-teraryls possessing an anthraquinone structure in good yields with good enantio- and diastereoselectivities. We have also determined that a thermal intramolecular [4+2] cycloaddition of 1,2-bis(arylpropiolyl)benzenes proceeds at 60 degrees C to give aryl-substituted naphthacenediones in moderate to good yields. PMID- 17288482 TI - Simplified synthesis of 3-(1-arylsulfonylalkyl) indoles and their reaction with Reformatsky reagents. AB - A simple procedure for the preparation of 3-(1-arylsulfonyl-alkyl) indoles by three-component condensation of indoles, carbonyls, and arenesulfinic acids is presented. The obtained products undergo a Reformatsky reaction leading to alkyl 3-(3-indolyl) alkanoates and (3-indolyl) ketones. PMID- 17288485 TI - Deformation-driven electrical transport of individual boron nitride nanotubes. AB - In contrast to standard metallic or semiconducting graphitic carbon nanotubes, for years their structural analogs, boron nitride nanotubes, in which alternating boron and nitrogen atoms substitute for carbon atoms in a graphitic network, have been considered to be truly electrically insulating due to a wide band gap of layered BN. Alternatively, here, we show that under in situ elastic bending deformation at room temperature inside a 300 kV high-resolution transmission electron microscope, a normally electrically insulating multiwalled BN nanotube may surprisingly transform to a semiconductor. The semiconducting parameters of bent multiwalled BN nanotubes squeezed between two approaching gold contacts inside the pole piece of the microscope have been retrieved based on the experimentally recorded I-V curves. In addition, the first experimental signs suggestive of piezoelectric behavior in deformed BN nanotubes have been observed. PMID- 17288486 TI - Mechanically responding nanovalves based on polyelectrolyte multilayers. AB - The alternate deposition of exponentially and linearly growing polyelectrolyte multilayers leads to the formation of multicompartment films. In this study, a new system consisting in nanometer-sized multilayer barriers deposited on or between multilayer compartments was designed to respond to mechanical stimuli and to act as nanovalves. The diffusion of polyelectrolytes through the barrier from one compartment to another can be switched on/off by tuning the mechanical stretching and thereby opening or closing nanopores in the barrier. This work represents a first step toward the design of chemically or biologically active films responding to mechanical stresses. PMID- 17288487 TI - Fabrication of field-effect transistors from hexathiapentacene single-crystal nanowires. AB - This paper describes a simple, solution-phase route to the synthesis of bulk quantities of hexathiapentacene (HTP) single-crystal nanowires. These nanowires have also been successfully incorporated as the semiconducting material in field effect transistors (FETs). For devices based on single nanowires, the carrier mobilities and current on/off ratios could be as high as 0.27 cm2/Vs and >103, respectively. For transistors fabricated from a network of nanowires, the mobilities and current on/off ratios could reach 0.057 cm2/Vs and >104, respectively. We have further demonstrated the use of nanowire networks in fabricating transistors on mechanically flexible substrates. Preliminary results show that these devices could withstand mechanical strain and still remain functional. The results from this study demonstrate the potential of utilizing solution-dispersible, nanostructured organic materials for use in low-cost, flexible electronic applications. PMID- 17288488 TI - Effect of spatial confinement on the glass-transition temperature of patterned polymer nanostructures. AB - Poly(methyl methacrylate) (PMMA) nanostructures embedded with a fluorescence tag are fabricated using electron beam lithography on oxidized silicon substrates. The glass transition temperatures (Tgs) of these one-dimensional (1-D) nanostructures (parallel lines) are measured by monitoring their temperature dependent fluorescence intensities, revealing substantial differences between the Tgs of the nanostructures and the thin films from which they were fabricated. For example, the Tg of 50-nm-wide PMMA nanolines on silica is approximately 15 K lower than that of a PMMA film on silica of the same 18 nm thickness. Attractive PMMA-silica interfacial interactions increase the Tg, while free surfaces decrease the Tg of PMMA in ultrathin films relative to bulk PMMA. Thus, the significant differences between the Tgs of the 1-D and two-dimensional (2-D) forms of PMMA on silica are the result of a substantial increase in the ratio of free-surface area to interfacial area in the PMMA nanolines relative to ultrathin films. PMID- 17288489 TI - Charge-associated effects of fullerene derivatives on microbial structural integrity and central metabolism. AB - The effects of four types of fullerene compounds (C60, C60-OH, C60-COOH, C60-NH2) were examined on two model microorganisms (Escherichia coli W3110 and Shewanella oneidensis MR-1). Positively charged C60-NH2 at concentrations as low as 10 mg/L inhibited growth and reduced substrate uptake for both microorganisms. Scanning electron microscopy (SEM) revealed damage to cellular structures. Neutrally charged C60 and C60-OH had mild negative effects on S. oneidensis MR-1, whereas the negatively charged C60-COOH did not affect either microorganism's growth. The effect of fullerene compounds on global metabolism was further investigated using [3-13C]L-lactate isotopic labeling, which tracks perturbations to metabolic reaction rates in bacteria by examining the change in the isotopic labeling pattern in the resulting metabolites (often amino acids).1-3 The 13C isotopomer analysis from all fullerene-exposed cultures revealed no significant differences in isotopomer distributions from unstressed cells. This result indicates that microbial central metabolism is robust to environmental stress inflicted by fullerene nanoparticles. In addition, although C60-NH2 compounds caused mechanical stress on the cell wall or membrane, both S. oneidensis MR-1 and E. coli W3110 can efficiently alleviate such stress by cell aggregation and precipitation of the toxic nanoparticles. The results presented here favor the hypothesis that fullerenes cause more membrane stress 4-6 than perturbation to energy metabolism.7. PMID- 17288490 TI - Quantum rod bioconjugates as targeted probes for confocal and two-photon fluorescence imaging of cancer cells. AB - Live cell imaging using CdSe/CdS/ZnS quantum rods (QRs) as targeted optical probes is reported. The QRs, synthesized in organic media using a binary surfactant mixture, were dispersed in aqueous media using mercaptoundecanoic acid (MUA) and lysine. Transferrin (Tf) was linked to the QRs to produce QR-Tf bioconjugates that were used for targeted in vitro delivery to a human cancer cell line. Confocal and two-photon imaging were used to confirm receptor-mediated uptake of QR-Tf conjugates into the HeLa cells, which overexpress the transferrin receptor (TfR). Uptake was not observed with QRs that lacked Tf functionalization or with cells that were presaturated with free Tf and then treated with Tf functionalized QRs. PMID- 17288491 TI - Rhodium nanoparticles from cluster seeds: control of size and shape by precursor addition rate. AB - The size-tunable synthesis of poly(vinylpyrrolidone)-stabilized cuboctahedral rhodium nanoparticles with mean diameters ranging between 3-7 nm and multipod structures was accomplished using seeded growth methods. Isotropic PVP-capped 2.9 nm seeds were prepared by ligand exchange on rhodium-triphenylphosphine metal organic clusters. Quantitative investigation of reaction parameters in ethylene glycol revealed that size and shape could be controlled at a single reaction temperature of 120 degrees C. The rate of rhodium monomer addition was found to be critical for monodispersity and shape control, regardless of thermodynamic factors. Solvent viscosity, varied by changing the polyol solvents, indicated that autocatalytic addition kinetics are responsible for isotropic versus anisotropic growth. PMID- 17288493 TI - Sodium fluoroacetate poisoning. AB - Sodium fluoroacetate was introduced as a rodenticide in the US in 1946. However, its considerable efficacy against target species is offset by comparable toxicity to other mammals and, to a lesser extent, birds and its use as a general rodenticide was therefore severely curtailed by 1990. Currently, sodium fluoroacetate is licensed in the US for use against coyotes, which prey on sheep and goats, and in Australia and New Zealand to kill unwanted introduced species. The extreme toxicity of fluoroacetate to mammals and insects stems from its similarity to acetate, which has a pivotal role in cellular metabolism. Fluoroacetate combines with coenzyme A (CoA-SH) to form fluoroacetyl CoA, which can substitute for acetyl CoA in the tricarboxylic acid cycle and reacts with citrate synthase to produce fluorocitrate, a metabolite of which then binds very tightly to aconitase, thereby halting the cycle. Many of the features of fluoroacetate poisoning are, therefore, largely direct and indirect consequences of impaired oxidative metabolism. Energy production is reduced and intermediates of the tricarboxylic acid cycle subsequent to citrate are depleted. Among these is oxoglutarate, a precursor of glutamate, which is not only an excitatory neurotransmitter in the CNS but is also required for efficient removal of ammonia via the urea cycle. Increased ammonia concentrations may contribute to the incidence of seizures. Glutamate is also required for glutamine synthesis and glutamine depletion has been observed in the brain of fluoroacetate-poisoned rodents. Reduced cellular oxidative metabolism contributes to a lactic acidosis. Inability to oxidise fatty acids via the tricarboxylic acid cycle leads to ketone body accumulation and worsening acidosis. Adenosine triphosphate (ATP) depletion results in inhibition of high energy-consuming reactions such as gluconeogenesis. Fluoroacetate poisoning is associated with citrate accumulation in several tissues, including the brain. Fluoride liberated from fluoroacetate, citrate and fluorocitrate are calcium chelators and there are both animal and clinical data to support hypocalcaemia as a mechanism of fluoroacetate toxicity. However, the available evidence suggests the fluoride component does not contribute. Acute poisoning with sodium fluoroacetate is uncommon. Ingestion is the major route by which poisoning occurs. Nausea, vomiting and abdominal pain are common within 1 hour of ingestion. Sweating, apprehension, confusion and agitation follow. Both supraventricular and ventricular arrhythmias have been reported and nonspecific ST- and T-wave changes are common, the QTc may be prolonged and hypotension may develop. Seizures are the main neurological feature. Coma may persist for several days. Although several possible antidotes have been investigated, they are of unproven value in humans. The immediate, and probably only, management of fluoroacetate poisoning is therefore supportive, including the correction of hypocalcaemia. PMID- 17288494 TI - Management of lithium toxicity. AB - Lithium salts have been used in the prophylaxis and treatment of depression and bipolar disorder for >50 years. Lithium has a narrow therapeutic range, and several well characterised adverse effects limit the potential usefulness of higher doses. Acute ingestion in lithium-naive patients is generally associated with only short-lived exposure to high concentrations, due to extensive distribution of lithium throughout the total body water compartment. Conversely, chronic toxicity and acute-on-therapeutic ingestion are associated with prolonged exposure to higher tissue concentrations and, therefore, greater toxicity. Lithium toxicity may be life threatening, or result in persistent cognitive and neurological impairment. Therefore, enhanced lithium clearance has been explored as a means of minimising exposure to high tissue concentrations. Although haemodialysis is highly effective in removing circulating lithium, serum concentrations often rebound so repeated or prolonged treatment may be required. Continuous arteriovenous haemodiafiltration and continuous venovenous haemodiafiltration increase lithium clearance, albeit to a lesser extent than haemodialysis, and are more widely accessible. Haemodiafiltration sustained for >16 hours allows effective removal of total body lithium, thereby avoiding rebound effects. Enhanced elimination should be considered in patients at greatest risk of severe poisoning: namely those with chronic or acute-on therapeutic toxicity, those with clinically significant features, and those with chronic toxicity whose serum lithium concentration is >2.5 mmol/L. The choice between haemodialysis and continuous haemodiafiltration techniques will depend on local accessibility and urgency of enhancing lithium elimination. Further research is required to establish the potential benefits of assisted elimination on clinical outcome in patients with lithium poisoning. PMID- 17288495 TI - Development of the bisquaternary oxime HI-6 toward clinical use in the treatment of organophosphate nerve agent poisoning. AB - The traditional therapeutic treatment of organophosphate cholinesterase inhibitor (nerve agents) poisoning consists of co-treatment with an antimuscarinic (atropine) and a reactivator of inhibited acetylcholinesterase (AChE), which contains a nucleophilic oxime function. Two oximes are presently widely available for clinical use, pralidoxime and obidoxime (toxogonin), but both offer little protection against important nerve agent threats. This has highlighted the real need for the development and availability of more effective oximes for human use, a search that has been going on for up to 30 years. However, despite the demonstration of more effective and safe oximes in animal experiments, no additional oximes have been licensed for human use. HI-6, (1-[[[4(aminocarbonyl) pyridinio]methoxy]methyl]-2(hydroxyimino)pyridinium dichloride; CAS 34433-31-3) has been studied intensively and has been proved effective in a variety of species including non-human primates and appears from clinical experience to be safe in humans. These studies have led to the fielding of HI-6 for use against nerve agents by the militaries of the Czech republic, Sweden, Canada and under certain circumstances the Organisation for the Prohibition of Chemical Weapons. Nevertheless HI-6 has not been granted a license for clinical use, must be used only under restricted guidelines and is not available for civilian use as far as is known. This article will highlight those factors relating to HI-6 that pertain to the licensing of new compounds of this type, including the mechanism of action, the clinical and pre-clinical demonstration of safety and its efficacy against a variety of nerve agents particularly in non-human primates, since no relevant human population exists. This article also contains important data on the use of HI-6 in baboons, which has not been available previously. The article also discusses the possibility of successful therapy with HI-6 against poisoning in humans relative to doses used in non-human primates and relative to its ability to reactivate inhibited human AChE. PMID- 17288496 TI - Nanotechnology and nanotoxicology: a primer for clinicians. AB - Nanotechnology is the manipulation of matter in dimensions <100 nm. At this size, matter can take on different chemical and physical properties, giving the products characteristics useful to industry, medicine and technology. Government funding and private investors provide billions of research dollars for the development of new materials and applications. The potential utility of these technologies is such that they are expected be a trillion-dollar industry within the next 10 years. However, the novel properties of nanoengineered materials lead to the potential for different toxicity compared with the bulk material. The field of nanotoxicology is still in its infancy, however, with very limited literature regarding potential health effects. Inhalational toxicity is to be expected, given the known effects of inhaled fine particulate matter. However, the degree to which most nanoparticles will aerosolise remains to be determined. It has been proposed that dermal exposure will be the most relevant route of exposure, but there is considerably less literature regarding dermal effects and absorption. Less defined still are the potential effects of nanoproducts on fetal development and the environment. PMID- 17288497 TI - Diacetyl-induced lung disease. AB - Diacetyl is a diketone flavouring agent that is commonly employed for buttery taste as well as other purposes. Industrial exposure to flavouring agents, particularly diacetyl, has recently been associated with bronchiolitis obliterans, a severe respiratory illness producing fibrosis and obstruction of the small airways. This has been most commonly reported in the microwave popcorn production industry, but it has occurred elsewhere. In addition to bronchiolitis obliterans, spirometry abnormalities (fixed airflow obstruction) and respiratory symptoms have been associated with exposure. A direct effect on the respiratory epithelium with the disorganised fibrotic repair appears most likely as the underlying mechanism. Current data suggest that diacetyl is the agent responsible, although it is possible that diacetyl is simply a marker for another causative agent. PMID- 17288498 TI - Therapeutic drug monitoring of digoxin: impact of endogenous and exogenous digoxin-like immunoreactive substances. AB - Digoxin is a cardioactive drug with a narrow therapeutic range. Therapeutic drug monitoring is essential in clinical practice for efficacy as well as to avoid digoxin toxicity. Immunoassays are commonly used in clinical laboratories for determination of serum or plasma digoxin concentrations. Unfortunately, digoxin immunoassays are affected by both endogenous and exogenous compounds. Endogenous compounds are termed 'digoxin-like immunoreactive substances' (DLIS), which are found in elevated concentrations in volume-expanded patients. Exogenous compounds that interfere with digoxin assays are various drugs such as spironolactone, potassium canrenoate as well as Digibind (Fab fragment of antidigoxin antibody), which is used in treating life-threatening digoxin overdose. Moreover, various Chinese medicines such as Chan Su, Lu-Shen Wan and oleander-containing herbal preparations also interfere with serum digoxin measurements by immunoassays. Monitoring unbound (free) digoxin concentration may under certain circumstances eliminate such interferences. Clinicians should be aware of limitations of therapeutic drug monitoring of digoxin using immunoassays. PMID- 17288499 TI - A critical reconsideration of the clinical effects and treatment recommendations for sodium channel blocking drug cardiotoxicity. AB - The cardiac sodium channel is comprised of proteins that span the cardiac cell membrane and form the channel pore. Depolarisation causes the proteins to move and open the sodium channel. Once the channel is open (active conformation), sodium ions move into the cell. The channel then changes from the active conformation to an inactive conformation - the channel remains open, but influx of sodium ions ceases. Recovery occurs as the channel moves from the inactive conformation back to the closed conformation and is then ready to open following the next depolarisation. Sodium channel blocking drugs (NCBDs) occupy receptors in the channel during the active and inactive conformations. The drug dissociates from most of the channel receptors during recovery, but the time it takes the drug to dissociate slows recovery. The slowed recovery prolongs conduction time, the main toxicity of NCBD overdose. Conduction time is further prolonged if heart rate increases as there are more available active and inactive conformations/unit time, which increases channel receptor binding sites for the NCBD. In addition to prolonging conduction time, NCBDs also decrease inotropy. Treatment of NCBD cardiotoxicity has been based on in vitro and animal experiments, and case reports. Assumptions based on this evidence must now be reassessed. For example, canines consistently develop ventricular tachycardia (VT) when tricyclic antidepressants (TCAs) are administered. Much of the literature discussing NCBD cardiotoxicity assumes that TCA poisoning induces VT in humans with the same regularity that occurs in canines. Seemingly, in support of this assumption was the finding that patients with remote myocardial infarction developed VT when therapeutically ingesting a NCBD. However, conduction is prolonged in myocardium that is or has been ischaemic. NCBD prolong conduction more in previously ischaemic myocardium than in normal myocardium, which causes nonuniform conduction and allows the development of re-entrant arrhythmias such as VT. Although some nonuniform conduction may occur in the healthy heart following a NCBD overdose, there is no evidence that nonuniform conduction occurs to the extent that it will cause re-entrant arrhythmias in this setting. Using various animal models and a variety of NCBDs, sodium ions, bicarbonate ions and alkalosis have been compared for the treatment of ventricular arrhythmias, hypotension and mortality. The results of these experiments have been extrapolated to NCBD overdose in humans. Animal models and single treatment approaches may have narrowed our scope. More recent evidence indicates that properties of each individual NCBD may require unique treatment. There is limited evidence that glucagon, which increases initial sodium ion influx into the cardiac cell, should be considered early in the treatment of cardiotoxicity. Another consideration may be treatment of NCBD with faster kinetics. Conduction time is decreased if a NCBD occupying the receptor is replaced by a NCBD that moves off and on the receptor more quickly. There is less evidence for this treatment, as risk may be greater. With greater understanding of the sodium channel and NCBDs, we must reassess our approach to the treatment of patients with healthy hearts who overdose on NCBD. PMID- 17288500 TI - The role of oximes in the treatment of nerve agent poisoning in civilian casualties. AB - There are important differences between on-target military attacks against relatively well protected Armed Forces and nerve agent attacks initiated by terrorists against a civilian population. In contrast to military personnel, civilians are unlikely to be pre-treated with pyridostigmine and protected by personal protective equipment. Furthermore, the time after exposure when specific therapy can first be administered to civilians is likely to be delayed. Even conservative estimates suggest a delay between exposure and the first administration of atropine/oxime of at least 30 minutes. The organophosphorus nerve agents are related chemically to organophosphorus insecticides and have a similar mechanism of toxicity, but a much higher mammalian acute toxicity, particularly via the dermal route. Nerve agents phosphonylate a serine hydroxyl group in the active site of the enzyme, acetylcholinesterase (AChE), which results in accumulation of acetylcholine and, in turn, causes enhancement and prolongation of cholinergic effects and depolarisation blockade. The rate of spontaneous reactivation of AChE is variable, which partly accounts for differences in acute toxicity between the nerve agents. With soman in particular, an additional reaction occurs known as 'aging'. This consists of monodealkylation of the dialkylphosphonyl enzyme, which is then resistant to spontaneous hydrolysis and reactivation by oximes. Monodealkylation occurs to some extent with all dialkylphosphonylated AChE complexes; however, in general, is only of clinical importance in relation to the treatment of soman poisoning, where it is a very serious problem. With soman, aging occurs so fast that no clinically relevant spontaneous reactivation of AChE occurs before aging has taken place. Hence, recovery of function depends on resynthesis of AChE. As a result, it is important that an oxime is administered as soon after soman exposure as possible so that some reactivation of AChE occurs before all the enzyme becomes aged. Even though aging occurs more slowly and reactivation occurs relatively rapidly in the case of nerve agents other than soman, early oxime administration is still clinically important in patients poisoned with these agents. Experimental studies on the treatment of nerve agent poisoning have to be interpreted with caution. Some studies have used prophylactic protocols, whereas the drugs concerned (atropine, oxime, diazepam) would only be given to a civilian population after exposure. The experimental use of pyridostigmine before nerve agent exposure, although rational, is not of relevance in the civilian context. With the possible exception of the treatment of cyclosarin (GF) and soman poisoning, when HI-6 might be preferred, a review of available experimental evidence suggests that there are no clinically important differences between pralidoxime, obidoxime and HI-6 in the treatment of nerve agent poisoning, if studies employing pre treatment with pyridostigmine are excluded. PMID- 17288501 TI - Overview of key data from the European Study of the Epidemiology of Mental Disorders (ESEMeD). AB - The European Study of the Epidemiology of Mental Disorders (ESEMeD) is the first large-scale survey to collect data comprehensively on the prevalence, risk factors, disability, and use of health care services associated with mood, anxiety, and alcohol-related disorders throughout Europe. Findings from the ESEMeD study are updated using a modified version of the Composite International Diagnostic Interview 3.0 in order to achieve the maximum diagnostic accuracy. The study is based on a sample of 21,425 noninstitutionalized adults, representative of an overall population of more than 212 million from Belgium, France, Germany, Italy, the Netherlands, and Spain. In total, 25.9% of participants reported a lifetime presence of any mental disorder, and 11.5% had experienced a mental disorder during the past 12 months. Females, younger participants, the unmarried, and the unemployed were more at risk, and comorbidity was prevalent. Associated levels of disability and reductions in quality of life exceeded levels seen in patients with chronic physical conditions. Nevertheless, only 36.8% of participants with a mood disorder and 20.6% with an anxiety disorder sought help from health care services; of these, 20.7% received no treatment. ESEMeD data provide an epidemiologic basis for reform of mental health policy within Europe. PMID- 17288503 TI - Barriers to help-seeking, detection, and adequate treatment for anxiety and mood disorders: implications for health care policy. AB - Recently, the focus of health policies and initiatives has been directed toward mental health. More precisely, depressive and anxiety disorders have received particular attention because of their disabling outcomes and prevalence among most populations. Despite this increased interest, numerous issues regarding patients' willingness to seek treatment and the adequate recognition and treatment of these disorders by clinicians remain to be addressed. This article considers the factors that influence patients and physicians in their reticence to acknowledge and adequately treat depression and anxiety disorders. It also reviews the impact of society and the media, together with other factors relating to health care organization and administration that affect the treatment of depression and anxiety. In view of the multifaceted challenge involved, efforts to achieve a consensus in determining treatment for those with depressive and anxiety disorders are essential. A consensus will require easy, measurable, and reliable disability indicators; evidence that treatment of patients with varying levels of need is cost effective; and that persons who most need and would benefit from care can be reliably identified among the highly prevalent population of persons with more transient symptoms. Governments and other policymakers should be encouraged to provide appropriate coverage for access to primary and secondary care, the treatments required, and sufficient resources so that care is available when necessary. An important aspect of the challenge is to incorporate these efforts within the realistic constraints of primary care. PMID- 17288504 TI - Underrecognition of anxiety and mood disorders in primary care: why does the problem exist and what can be done? AB - Despite current debate on the methodology of existing research into depression and anxiety disorders, there is still general agreement that recognition rates of these conditions in primary care could be improved. This review examines the factors that influence recognition of these disorders from both the patients' perspective and the primary care givers' perspective. Approaches and methods for improving recognition in primary care, including guidelines, mental health skills training, screening, and increasing public awareness, are considered in detail. PMID- 17288505 TI - Mental illness, stigma, and the media. AB - Society is ingrained with prejudice toward mental illness, and sufferers are often widely perceived to be dangerous or unpredictable. Reinforcement of these popular myths through the media can perpetuate the stigma surrounding mental illness, precipitating shame, self-blame, and secrecy, all of which discourage affected individuals from seeking treatment. Efforts aimed at countering stigma in mental illness are faced with the challenge of centuries of discrimination and must, therefore, replace existing stereotypes with coverage of positive outcomes, as a first step in achieving the daunting task of overcoming these negative stereotypes. Long-term anti-stigma campaigns that encompass human-rights-based, normalization, and educational approaches are needed. The involvement of the media is essential for success, but, in order for the media to be used effectively, its motivations and limitations must first be recognized and understood. PMID- 17288502 TI - The global burden of anxiety and mood disorders: putting the European Study of the Epidemiology of Mental Disorders (ESEMeD) findings into perspective. AB - This article compares the preliminary, descriptive European Study of The Epidemiology of Mental Disorders (ESEMeD) findings reported in this supplement with 8 broad patterns of results found in previous psychiatric epidemiologic surveys. It is a systematic review of the literature on community epidemiologic surveys of anxiety and mood disorders. It concludes that the ESEMeD findings are broadly consistent with the patterns found in previous surveys but faults the preliminary ESEMeD analyses for failing to distinguish cases by severity and to consider the effects of severity on need for treatment. The fact that the ESEMeD surveys collected much richer data than previous psychiatric epidemiologic surveys on role impairment, symptom severity, and episode duration makes it possible to develop more useful classifications of clinical severity in future analyses. Elaborations that feature such distinctions have the potential to substantially increase the relevance of the ESEMeD findings for European health care policy. PMID- 17288506 TI - Widespread underrecognition and undertreatment of anxiety and mood disorders: results from 3 European studies. AB - Data from the World Health Organization (WHO) Collaborative Study on Psychological Problems in General Health Care, which was conducted in 26,422 primary care attendees in 14 countries worldwide, and from the Institut National de la Sante et de la Recherche Medicale (INSERM) study, which was conducted in over 2400 consecutive primary care patients in France, demonstrate the high prevalence of major depression in general practice (13.7% and 14.0% in each study, respectively). These 2 studies are supported by the more recent European Study of the Epidemiology of Mental Disorders (ESEMeD), which was conducted in over 21,400 adults from the general populations of 6 European countries and which revealed a lifetime prevalence rate for major depression of 13.4%. Despite this high prevalence, both the WHO and INSERM studies revealed that only 54% to 58% of depressed patients were recognized as "psychiatric cases" by their general practitioner and only 15% to 26% were given a specific diagnosis of depression. Even when cases were recognized, treatment was frequently inappropriate. In the WHO study, only 43% of patients correctly diagnosed with depression by their general practitioner were prescribed an antidepressant, and only 31% of patients recognized as "anxious" received an anxiolytic agent (14% were prescribed an antidepressant). In the ESEMeD study, only 4.6% of adults diagnosed with depression were using antidepressants exclusively, and 18.4% had used anxiolytic medications exclusively. The willingness to prescribe antidepressants and anxiolytic agents is influenced, in part, by diagnosis, patient age and gender, comorbidity (and severity), and the number of spontaneous psychological complaints. PMID- 17288507 TI - Consensus statement on the benefit to the community of ESEMeD (European Study of the Epidemiology of Mental Disorders) survey data on depression and anxiety. AB - OBJECTIVE: To provide an overview of the importance of the data generated by the European Study of the Epidemiology of Mental Disorders (ESEMeD), which found that prevalence and burden of mood and anxiety disorders were high and that care of individuals with mental disorders was suboptimal. Thus, ESEMeD data, based on 21,425 noninstitutionalized adults from Belgium, France, Germany, Italy, the Netherlands, and Spain who underwent computer-assisted personal interviews, confirmed previous findings from epidemiologic studies performed in other locations. In addition, how this large and unique dataset may be utilized for maximum benefit to patients is outlined. PARTICIPANTS: The co-chairmen David J. Nutt, M.D., Ph.D., and Ronald C. Kessler, Ph.D., invited 6 faculty members to participate: Jordi Alonso, M.D., Ph.D.; Alastair Benbow, M.B., M.R.C.P.I.; Yves Lecrubier, M.D.; Jean-Pierre Lepine, M.D.; David Mechanic, Ph.D.; and Andre Tylee, M.D. EVIDENCE: The consensus statement is based on the 6 review articles published in this supplement, which include ESEMeD data and data from pertinent scientific literature. CONSENSUS PROCESS: The faculty met over a 2-day period: day 1 included discussion of the review articles, during which the chairmen identified issues for further debate; day 2 included discussion of key issues to arrive at a consensus view. The consensus view was drafted by the chairmen and approved by all attendees. CONCLUSIONS: ESEMeD provides a very important opportunity to improve knowledge on the epidemiology of mood and anxiety disorders. Despite a decade of educational initiatives, the diagnosis and treatment of mood and anxiety disorders remain suboptimal. Lack of awareness and stigma surrounding mental illness, variations in physicians' ability to diagnose and treat psychiatric conditions, and physician time pressures all contribute to the problem. Future education initiatives should include patients, primary care physicians, employers, and health policy influencers. Patients with mood and anxiety disorders may benefit from targeted antidepressant treatment, which should optimize the chance of patients' receiving appropriate therapy. In addition, depending on the patients' circumstances, psychotherapy, counseling, or social support may also be initiated. PMID- 17288509 TI - Proteomics in the study of organ dysfunction. PMID- 17288508 TI - Relationship between vaccine vial monitors and cold chain infrastructure in a rural district of India. AB - INTRODUCTION: The potency of oral polio vaccine (OPV), a heat-labile vaccine, is preserved by the cold chain. The Vaccine Vial Monitor, a heat-sensitive label, is critical to the monitoring and maintenance of the cold chain. This study was conducted to evaluate the relationship between the adequacy of cold chain infrastructure and the proper use of Vaccine Vial Monitor in a rural district of India. METHODS: Forty-six health centers in a rural district were included in our evaluation of the cold chain equipment and the Vaccine Vial Monitors. Cold chain equipment and vaccine vials within each health center were evaluated for adherence to WHO cold chain maintenance protocols and the Vaccine Vial Monitor stage, respectively. RESULTS: Among the 46 health centers, Vaccine Vial Monitor stage I was found at 58% of the health centers, 33% of the health centers reported stage II and 9% reported a stage III, indicating weaknesses in the cold chain mechanism CONCLUSION: Cold chain for the OPV was not adequately maintained at primary and sub-health centers in this rural district. Well maintained ice packs and vaccine carriers will help ensure delivery and availability of a safe and potent vaccine to children in rural areas of India. PMID- 17288511 TI - Clinical proteomics: opportunities for diagnostics, pharmaceuticals and the clinical laboratory. PMID- 17288512 TI - Quantitative proteomic approaches for studying phosphotyrosine signaling. AB - Protein tyrosine phosphorylation is a fundamental mechanism for controlling many aspects of cellular processes, as well as aspects of human health and diseases. Compared with phosphoserine and phosphothreonine, phosphotyrosine signaling is more tightly regulated, but often more challenging to characterize, due to significantly lower levels of tyrosine phosphorylation (i.e., a relative abundance of 1800:200:1 was estimated for phosphoserine/phosphothreonine/phosphotyrosine in vertebrate cells). In this review, we outline recent advances in analytical methodologies for enrichment, identification and accurate quantitation of tyrosine-phosphorylated proteins and peptides. Advances in antibody-based technologies, capillary liquid chromatography coupled with mass spectrometry, and various stable isotope labeling strategies are discussed, as well as non-mass spectrometry-based methods, such as those using protein/peptide arrays. As a result of these advances, powerful tools now have the power to crack signal transduction codes at the system level, and provide a basis for discovering novel drug targets for human diseases. PMID- 17288513 TI - Amino acid-coded tagging approaches in quantitative proteomics. AB - To improve the efficiency, accuracy, reproducibility, throughput and proteome coverage of mass spectrometry-based quantitative approaches, both in vitro and in vivo tagging of particular amino acid residues of cellular proteins have been introduced to assist mass spectrometry for global-scale comparative studies of differentially expressed proteins/modifications between different biologically relevant cell states or cells at different pathological states. The basic features of these methods introduce pair-wise isotope signals of each individual peptide containing a particular type of tagged amino acid (amino acid-coded mass tagging) that originated from different cell states. In this review, the applications of major amino acid-coded mass tagging-based quantitative proteomics approaches, including isotope-coded affinity tag, isobaric tags for relative and absolute quantification (iTRAQ) and stable isotope labeling by amino acids in cell culture are summarized in the context of their respective strengths/weakness in identifying those differentially expressed or post-translational modified proteins regulated by particular cellular stress on a genomic scale in a high throughput manner. Importantly, these gel-free, in-spectra quantitative mechanisms have been further explored to identify/characterize large-scale protein-protein interactions involving various functional pathways. Taken together, the information about quantitative proteome changes, including multiple regulated proteins and their interconnected relationships, will provide an important insight into the molecular mechanisms, where novel targets for diagnosis and therapeutic intervention will be identified. PMID- 17288514 TI - Urinary proteomics: a tool to discover biomarkers of kidney diseases. AB - There is intense interest in applying proteomics to urine analysis in order to promote a better understanding of kidney disease processes, develop new biomarkers for diagnosis and detect early factors that contribute to end-stage renal diseases. This interest creates numerous opportunities as well as challenges. To fulfill this task, proteomics requires, in its different stages of realization, various technological platforms with high sensitivity, high throughput and large automation ability. In this review, we will give an overview of promising proteomic methods that can be used for analyzing urinary proteome and detecting biomarkers for different kidney diseases. Furthermore, we will focus on the current status and future directions in investigating kidney diseases using urinary proteomics. PMID- 17288515 TI - Opportunities and limitations of SELDI-TOF-MS in biomedical research: practical advices. AB - Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, or surface-enhanced laser desorption/ionization ProteinChip technology, has been widely used in obtaining the quantitative profiles of tissue proteomes, particularly plasma proteomes. Its high-throughput nature and simplicity in its experimental procedures have allowed this technology to become a popular research tool for biomarker discovery in the past 5 years. After accumulating more research experiences, researchers now have a better understanding of the characteristics and limitations of this technology, as well as the pitfalls in biomarker research, by undertaking a comparative proteomic approach. This review provides an overview of the surface-enhanced laser desorption/ionization time-of flight mass spectrometry, discusses its limitations and provides some possible solutions to help apply this technology to biomarker research. PMID- 17288516 TI - Optimization of protein expression systems for modern drug discovery. AB - The expression of high levels of stable and functional proteins remains a bottleneck in many scientific endeavors, including the determination of structures in a high-throughput fashion or the screening for novel active compounds in modern drug discovery. Recently, numerous developments have been made to improve the production of soluble and active proteins in heterologous expression systems. These include modifications to the expression constructs, the introduction of new and/or improved pro- and eukaryotic expression systems, and the development of improved cell-free protein synthesis systems. The introduction of robotics has enabled a massive parallelization of expression experiments, thereby vastly increasing the throughput and, hopefully, the output of such experiments. In addition, the big challenges of recombinant overexpression of membrane and secreted proteins are tackled, and some new methods are reviewed. PMID- 17288517 TI - Production of membrane proteins using cell-free expression systems. AB - Different overexpression systems are widely used in the laboratory to produce proteins in a reasonable amount for functional and structural studies. However, to optimize these systems without modifying the cellular functions of the living organism remains a challenging task. Cell-free expression systems have become a convenient method for the high-throughput expression of recombinant proteins, and great effort has been focused on generating high yields of proteins. Furthermore, these systems represent an attractive alternative for producing difficult-to express proteins, such as membrane proteins. In this review, we highlight the recent improvements of these cell-free expression systems and their direct applications in the fields of membrane proteins production, protein therapy and modern proteomics. PMID- 17288518 TI - Bacterial outer membrane protein analysis by electrophoresis and microchip technology. AB - Outer membrane proteins are indispensable components of bacterial cells and participate in several relevant functions of the microorganisms. Changes in the outer membrane protein composition might alter antibiotic sensitivity and pathogenicity. Furthermore, the effects of various factors on outer membrane protein expression, such as antibiotic treatment, mutation, changes in the environment, lipopolysaccharide modification and biofilm formation, have been analyzed. Traditionally, the outer membrane protein profile determination was performed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Converting this technique to capillary electrophoresis format resulted in faster separation, lower sample consumption and automation. Coupling capillary electrophoresis with mass spectrometry enabled the fast identification of bacterial proteins, while immediate quantitative analysis permitted the determination of up- and downregulation of certain outer membrane proteins. Adapting capillary electrophoresis to microchip format ensured a further ten- to 100-fold decrease in separation time. Application of different separation techniques combined with various sensitive detector systems has ensured further opportunities in the field of high-throughput bacterial protein analysis. This review provides an overview using selected examples of outer membrane proteins and the development and application of the electrophoretic and microchip technologies for the analysis of these proteins. PMID- 17288519 TI - Systems biology approach to integrative comparative genomics. AB - As more and more systems biology approaches are used to investigate the different types of biological macromolecules, increasing numbers of whole genomic studies are now available for a large array of organisms. Whether it is genomics, transcriptomics, proteomics, interactomics or metabolomics, the full complement of genomic information on all different levels can be juxtaposed between different organisms to reveal similarities or differences, and even to provide consensus models. At the intersection of comparative genomics and systems biology lies great possibility for discovery, analysis and prediction. This paper explores this nexus and the relationship from four general levels: DNA, RNA, protein and extragenomic. For each level, we provide an overview of the methods, discuss the potential challenges and survey the current research. Finally, we suggest some organizing principles and make proposals for new areas that will be important for future research. PMID- 17288520 TI - Recent technical strategies to identify diagnostic biomarkers for ovarian cancer. AB - Ovarian cancer is the fifth leading cause of cancer deaths among North American women. Regrettably, there is currently no reliable circulating biomarker that can detect ovarian cancer in its early stages. The CA125 biomarker is very useful for treatment response monitoring, but its sensitivity is very low for early detection. Thus, there is an urgent need for the identification of new circulating biomarkers/panel of biomarkers that could be used to diagnose ovarian cancer before it becomes clinically detectable and advanced. Unfortunately, the strategies used in the past years to identify such biomarkers have not led to any outstanding candidate. This review summarizes the different approaches used in the last decade and suggests which strategies should be adopted in the near future in order to lead to the successful identification of new ovarian cancer diagnostic biomarkers. PMID- 17288522 TI - Clofarabine for the treatment of acute lymphoblastic leukemia. AB - A marked improvement in the outcome of patients with acute lymphoblastic leukemia has been achieved with chemotherapeutic agents developed between the 1950s and 1970s. As the limits of optimizing the use of old drugs are reached, most adults with acute lymphoblastic leukemia still succumb to their disease and leukemia remains the leading cause of nonaccidental death in children. Salvage regimens, based mostly on different combinations of the same agents used in front-line therapy, carry a high incidence of morbidity and dismal long-term survival rates. New therapeutic strategies are needed. Clofarabine, a next-generation deoxyadenosine analog, has demonstrated significant activity in children and adults with refractory lymphoid and myeloid leukemia in early clinical trials and was granted approval for use in children with acute lymphoblastic leukemia in second or higher relapse. This is the only anticancer drug to receive primary indication for use in children over the past decade. Ongoing studies are exploring the benefit of clofarabine combinations in less heavily pretreated patients and the use of different dose schedules in a variety of hematological malignancies. PMID- 17288523 TI - 7th annual International Conference on Ovarian Cancer. PMID- 17288524 TI - Partial-breast irradiation: towards a replacement for whole-breast irradiation? AB - Largely thanks to all of the investigators and patients who have participated in randomized breast-conservation trials, many women facing a diagnosis of breast cancer today can conserve their breast with the help of adjuvant radiation therapy. A standard course of radiation consists of 5-7 weeks of daily radiation treatments delivered to the whole breast. The success of this treatment has led investigators to attempt to determine whether the same control can be achieved while decreasing the volume of breast tissue irradiated, thus allowing treatment to be delivered in a shorter period of time. This approach could alleviate time and logistical problems faced by patients during their course of treatment as well as improving overall cost-effectiveness. It can also allow complete avoidance of the adjacent heart and lung tissue in the radiation treatment portal. Partial-breast irradiation (the delivery of radiation to the resection cavity, plus a safety margin) delivered in just hours or days, is currently under investigation. Although relatively new, its use is growing rapidly and many institutional and cooperative group trials are quickly enlisting patients, while physicians are gaining experience in a variety of partial-breast irradiation techniques. PMID- 17288525 TI - Biology and treatment of ductal carcinoma in situ. AB - Ductal carcinoma in situ (DCIS) is responsible for 25% of screen-detected breast cancers. Various prognostic classifications are in use, including the Van Nuys Prognostic Index and the European Organisation for Research and Treatment of Cancer grading system (well, intermediate or poorly differentiated) based on cytonuclear pattern. This has been modified in screening programs to low, intermediate and high grade. In comparison with normal epithelium, DCIS has a tenfold increase in growth and 15-fold increase in apoptosis. Patients with extensive or multifocal DCIS need mastectomy and sentinel node biopsy, together with reconstruction, if requested. Microinvasion associated with DCIS is an indication for sentinel node biopsy. Randomized trials have confirmed the value of breast irradiation after wide excision, in terms of DCIS relapse and progression to invasive disease. Patients with estrogen receptor-positive DCIS benefit from adjuvant tamoxifen after breast-conserving surgery. PMID- 17288526 TI - Cdc42: an effector and regulator of ErbB1 as a strategic target in breast cancer therapy. AB - ErbB1 and ErbB2 are often overexpressed in breast cancer. Overexpression of these receptors is correlated with poor prognosis. ErbB receptor-targeted therapies have been developed for the treatment of human breast cancer. While ErbB2 overexpression is usually caused by gene amplification, the mechanism for ErbB1 overexpression remains elusive. An important mechanism for the downregulation of ErbB1 is via Cbl-mediated receptor ubiquitination and degradation. Increasing evidence suggests that loss of Cbl-regulated ErbB1 degradation contributes to ErbB1 overexpression in cancer cells. Cdc42 is overexpressed in some breast cancers and evidence is accumulating that activated Cdc42 contributes to the accumulation of ErbB1 in cells through the regulation of c-Cbl function. Different therapeutic strategies targeting ErbB receptors and Cdc42 will be reviewed and discussed. PMID- 17288527 TI - Current concepts in multimodality therapy for retroperitoneal sarcoma. AB - Radical surgical resection currently represents the most effective therapy for patients with retroperitoneal sarcoma. Unfortunately, margin-negative resection often mandates extirpation of multiple retroperitoneal viscera, and such operations are nonetheless fraught with high rates of locoregional recurrence. In an attempt to improve local control and ultimately survival, adjuvant strategies of radiation and chemotherapy have been increasingly employed, with promising results. To date, however, the rarity of the disease has limited large, prospective studies investigating the efficacy of these adjuvant modalities. In this article, we review the current literature pertaining to the diagnosis, staging and treatment of retroperitoneal sarcoma and demonstrate the critical need for future large, multi-institutional studies to advance our knowledge of this uncommon disease. PMID- 17288528 TI - Recent advances in the management of osteosarcoma and forthcoming therapeutic strategies. AB - Osteosarcoma is the most frequent primary bone tumor and occurs mainly in young patients (average age: 18 years). No evolution of the survival rates has been recorded for two decades in response to current treatment, associating often toxic and badly tolerated cures of chemotherapy (given a significant rate of bad responders) with preserving surgery. Among the proposed innovative strategies, immune-based therapy, antiangiogenesis agents, tumor-suppressor or suicide gene therapy, or anticancer drugs not commonly used in osteosarcoma are presented. A further strategy is to target the tumor microenvironment rather than the tumor itself. PMID- 17288529 TI - Adult human sarcomas. II. Medical oncology. AB - Human sarcoma cells can be killed by radio- and chemotherapy, but tumor cells acquiring resistance frequently kill the patient. A keen understanding of the intracellular course of oncogenic cascades leads to the discovery of small molecular inhibitors of the involved phosphorylated kinases. Targeted therapy complements chemotherapy. Oncogene silencing is feasible by small interfering RNA. The restoration of some of the mutated or deleted tumor-suppressor genes (p53, Rb, PTEN, hSNF, INK/ARF and WT) by demethylation or reacetylation of their histones has been accomplished. Genetically engineered or naturally oncolytic viruses selectively lyse tumors and leave healthy tissues intact. Adeno- or retroviral vectors deliver genes of immunological costimulators, tumor antigens, chemo- or cytokines and/or tumor-suppressor proteins into tumor (sarcoma) cells. Suicide gene delivery results in apoptosis induction. Genes of enzymes that target prodrugs as their substrates render tumor cells highly susceptible to chemotherapy, with the prodrug to be targeted intracellularly. It will be combinations of sophisticated surgical removal of the nonencapsulated and locally invasive primary sarcomas, advanced forms of radiotherapy to the involved sites and immunotherapy with sarcoma vaccines that will cure primary sarcomas. Adoptive immunotherapy with immune lymphocytes will be operational in metastatic disease only when populations of regulatory T cells are controlled. Targeted therapy with small molecular inhibitors of oncogene cascades, the driving forces of sarcoma cells, alteration of the tumor stroma from a supportive to a tumor-hostile environment, reactivation or replacement of wild-type tumor-suppressor genes, and radio-chemotherapy (with much reduced toxicity) will eventually accomplish the cure of metastatic sarcomas. PMID- 17288530 TI - Kaposi sarcoma as a model of oncogenesis and cancer treatment. AB - Kaposi sarcoma is the most common cancer among HIV-infected individuals and one of the most common cancers in sub-Saharan Africa. Kaposi sarcoma lesions are highly vascularized, and comprised of spindle-shaped tumor cells. Kaposi sarcoma herpesvirus is etiologically linked to Kaposi sarcoma development and encodes genes that contribute to cellular transformation, evasion of apoptosis, aberrant angiogenesis and an inflammatory tumor microenvironment. The study of Kaposi sarcoma herpesvirus-driven malignancies has provided a model of oncogenesis and identified some of the key steps and, therefore, therapeutic targets of Kaposi sarcoma development. However, current Kaposi sarcoma treatments are not specific and rely on reconstitution of the immune system and systemic administration of cytotoxic agents. Recent studies have demonstrated that mechanism-based therapeutics, such as vascular endothelial growth factor A or mammalian target of rapamycin inhibitors, are promising therapeutic approaches bridging basic research with clinical practice. PMID- 17288531 TI - Key roles of the OPG-RANK-RANKL system in bone oncology. AB - Osteoprotegerin (OPG)-receptor activator of nuclear factor-kappaB (RANK) and RANK ligand (RANKL) have been identified as members of a ligand-receptor system that directly regulates osteoclast differentiation and osteolysis. RANKL may be a powerful inducer of bone resorption through its interaction with RANK, and OPG is a soluble decoy receptor that acts as a strong inhibitor of osteoclastic differentiation. Any dysregulation of their respective expression leads to pathological conditions. Furthermore, recent data demonstrate that the OPG-RANK RANKL system modulates cancer cell migration, thus controlling the development of bone metastases. This review describes the most recent knowledge on the OPG-RANK RANKL system, its involvement in bone oncology and the new therapeutic approaches based on this molecular triad. PMID- 17288532 TI - Management of tumor lysis syndrome in adults. AB - Spontaneous or treatment-induced tumor lysis syndrome (TLS) can cause significant morbidity and potential mortality. Vigorous hydration, alkalinization and inhibition of uric acid synthesis with allopurinol are the most frequently used methods for treatment and prevention of TLS. However, this approach fails to prevent renal insufficiency in up to 25% of high-risk patients. With the increased intensity and efficacy of cancer therapies, novel approaches for the management of TLS are needed. Unlike allopurinol, urate oxidase promptly reduces the existing uric acid pool, prevents accumulation of xanthine and hypoxanthine and does not require alkalinization, facilitating phosphorus excretion. A recombinant form of urate oxidase, rasburicase, is now registered for the treatment and prevention of TLS. This review provides an overview of rasburicase development and discusses the impact of rasburicase in the prevention and management of TLS. PMID- 17288534 TI - Oxidative modifications to cellular components in plants. AB - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced in many places in living cells and at an increased rate during biotic or abiotic stress. ROS and RNS participate in signal transduction, but also modify cellular components and cause damage. We first look at the most common ROS and their properties. We then consider the ways in which the cell can regulate their production and removal. We critically assess current knowledge about modifications of polyunsaturated fatty acids (PUFAs), DNA, carbohydrates, and proteins and illustrate this knowledge with case stories wherever possible. Some oxidative breakdown products, e.g., from PUFA, can cause secondary damage. Other oxidation products are secondary signaling molecules. We consider the fate of the modified components, the energetic costs to the cell of replacing such components, as well as strategies to minimize transfer of oxidatively damaged components to the next generation. PMID- 17288535 TI - Insights from crystallographic studies into the structural and pairing properties of nucleic acid analogs and chemically modified DNA and RNA oligonucleotides. AB - Chemically modified nucleic acids function as model systems for native DNA and RNA; as chemical probes in diagnostics or the analysis of protein-nucleic acid interactions and in high-throughput genomics and drug target validation; as potential antigene-, antisense-, or RNAi-based drugs; and as tools for structure determination (i.e., crystallographic phasing), just to name a few. Biophysical and structural investigations of chemically modified DNAs and RNAs, particularly of nucleic acid analogs with more significant alterations to the well-known base sugar-phosphate framework (i.e., peptide or hexopyranose nucleic acids), can also provide insights into the properties of the natural nucleic acids that are beyond the reach of studies focusing on DNA or RNA alone. In this review we summarize results from crystallographic analyses of chemically modified DNAs and RNAs that are primarily of interest in the context of the discovery and development of oligonucleotide-based therapeutics. In addition, we re-examine recent structural data on nucleic acid analogs that are investigated as part of a systematic effort to rationalize nature's choice of pentose in the genetic system. PMID- 17288536 TI - Single-molecule fluorescence analysis of cellular nanomachinery components. AB - Recent progress in proteomics suggests that the cell can be conceived as a large network of highly refined, nanomachine-like protein complexes. This working hypothesis calls for new methods capable of analyzing individual protein complexes in living cells and tissues at high speed. Here, we examine whether single-molecule fluorescence (SMF) analysis can satisfy that demand. First, recent technical progress in the visualization, localization, tracking, conformational analysis, and true resolution of individual protein complexes is highlighted. Second, results obtained by the SMF analysis of protein complexes are reviewed, focusing on the nuclear pore complex as an instructive example. We conclude that SMF methods provide powerful, indispensable tools for the structural and functional characterization of protein complexes. However, the transition from in vitro systems to living cells is in the initial stages. We discuss how current limitations in the nanoscopic analysis of living cells and tissues can be overcome to create a new paradigm, nanoscopic biomedicine. PMID- 17288537 TI - Functional diversification of a basic helix-loop-helix protein due to alternative transcription during generation of amphidiploidy in tobacco plants. AB - A plastid-resident basic helix-loop-helix protein, previously identified in Nicotiana tabacum and designated as NtWIN4 (N. tabacum wound-induced clone 4), has been converted from a nuclear transcription repressor into a plastid-resident regulatory factor through replacement of the DNA-binding domain with a plastid transit sequence during evolution. N. tabacum is a natural amphidiploid plant derived from Nicotiana tomentosiformis and Nicotiana sylvestris and immunoblot staining using anti-NtWIN4 antibodies identified two protein species, a 26 kDa form and a 17 kDa form, in N. sylvestris, whereas only the 17 kDa form was found in N. tabacum. The 26 kDa protein is produced when translation starts from the first AUG codon of the mRNA and is predominantly localized in the cytoplasm and nucleus, whereas the 17 kDa protein is derived from a 24 kDa precursor protein, synthesized from the second AUG codon, and localizes only to plastids. Subsequent analyses revealed that the lengths of the mRNAs vary in the two plant species. One major form lacks the first AUG, while minor populations possess variable 5' untranslated regions prior to the first AUG codon. Translation of the two types produces the 24 kDa and 26 kDa proteins respectively. In vitro translation assays indicated that initiation frequency from the first AUG codon is higher in mRNAs from N. sylvestris than from N. tabacum. In contrast, initiation from the second AUG codon was found to be equally efficient in mRNAs from both species. These results suggest that both mRNA populations and translation efficiency changed during the amphidiploidization responsible for generation of N. tabacum. This scheme could reflect a molecular mechanism of protein evolution in plants. PMID- 17288538 TI - Phylogenetic and specificity studies of two-domain GNA-related lectins: generation of multispecificity through domain duplication and divergent evolution. AB - A re-investigation of the occurrence and taxonomic distribution of proteins built up of protomers consisting of two tandem arrayed domains equivalent to the GNA [Galanthus nivalis (snowdrop) agglutinin] revealed that these are widespread among monotyledonous plants. Phylogenetic analysis of the available sequences indicated that these proteins do not represent a monophylogenetic group but most probably result from multiple independent domain duplication/in tandem insertion events. To corroborate the relationship between inter-domain sequence divergence and the widening of specificity range, a detailed comparative analysis was made of the sequences and specificity of a set of two-domain GNA-related lectins. Glycan microarray analyses, frontal affinity chromatography and surface plasmon resonance measurements demonstrated that the two-domain GNA-related lectins acquired a marked diversity in carbohydrate-binding specificity that strikingly contrasts the canonical exclusive specificity of their single domain counterparts towards mannose. Moreover, it appears that most two-domain GNA-related lectins interact with both high mannose and complex N-glycans and that this dual specificity relies on the simultaneous presence of at least two different independently acting binding sites. The combined phylogenetic, specificity and structural data strongly suggest that plants used domain duplication followed by divergent evolution as a mechanism to generate multispecific lectins from a single mannose-binding domain. Taking into account that the shift in specificity of some binding sites from high mannose to complex type N-glycans implies that the two-domain GNA-related lectins are primarily directed against typical animal glycans, it is tempting to speculate that plants developed two-domain GNA-related lectins for defence purposes. PMID- 17288539 TI - Expression of the Longin domain of TI-VAMP impairs lysosomal secretion and epithelial cell migration. AB - BACKGROUND INFORMATION: TI-VAMP (tetanus neurotoxin-insensitive vesicle associated membrane protein; also called VAMP7) belongs to the Longin subfamily of v-SNAREs (vesicular soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors). The regulatory N-terminal extension, called the Longin domain, of TI-VAMP has been shown previously to have a dual biochemical function: it inhibits the capacity of TI-VAMP to form SNARE complexes and it binds to the delta subunit of the AP-3 (adaptor protein 3) complex in early endosomes, thereby targeting TI-VAMP to late endosomes. RESULTS: We have generated MDCK (Madin-Darby canine kidney) cell lines expressing the Longin domain of TI-VAMP coupled to GFP (green fluorescent protein) in a doxycycline dependent manner. As expected, AP-3delta (AP-3 delta subunit) is not properly localized in Longin-expressing cells. We have shown that the expression of the Longin domain impairs lysosomal secretion, as determined by the release of a pre internalized fluorescent fluid-phase marker and by electron microscopy of the membrane-associated released particles. Membrane repair following mechanical wounding, a process requiring lysosomal secretion, is also impaired in cells expressing the Longin domain. Furthermore, cell migration, assessed by wound healing of MDCK monolayers, is also inhibited. CONCLUSIONS: The results of the present study suggest that the expression of the Longin domain of TI-VAMP regulates lysosomal secretion of epithelial cells and provide molecular evidence for a role of the late endocytic system in cell migration. PMID- 17288541 TI - Conserved patterns of nuclear compartmentalization are not observed in the chordate Oikopleura. AB - BACKGROUND INFORMATION: Recent results from a limited number of eukaryotic model organisms suggest that major principles governing spatial organization of the genome in functionally distinct nuclear compartments are conserved through evolution. RESULTS: We examined the in situ spatial organization of major nuclear components and nuclear patterns of gene loci with strictly defined expression patterns in endocycling cells of the transparent urochordate Oikopleura dioica, a complex metazoan with a very compact genome. Endocycling cells with different functions and similar DNA content displayed distinct topologies of nuclear components. However, the generation of the diverse nuclear architectures did not involve specific local organization of active genes or their preferential amplification. Interestingly, endocycling cells lacked nuclear-envelope associated heterochromatin and prominent splicing-factor domains, which in mammalian cells associate with transcriptionally silent and active loci respectively. In addition, no correlation was found between transcriptional activity of a locus and its association with chromatin domains rich in specific histone modifications. CONCLUSIONS: Together, these findings and the absence of typical eukaryotic replication patterns reveal a surprisingly limited functional compartmentalization of O. dioica endocycling nuclei. This indicates that robust cell-type-specific gene expression does not necessarily require high levels of spatial genome organization. PMID- 17288540 TI - Mapping binding sites for the PDE4D5 cAMP-specific phosphodiesterase to the N- and C-domains of beta-arrestin using spot-immobilized peptide arrays. AB - Beta2-ARs (beta2-adrenoceptors) become desensitized rapidly upon recruitment of cytosolic beta-arrestin. PDE4D5 (family 4 cAMP-specific phosphodiesterase, subfamily D, isoform 5) can be recruited in complex with beta-arrestin, whereupon it regulates PKA (cAMP-dependent protein kinase) phosphorylation of the beta2-AR. In the present study, we have used novel technology, employing a library of overlapping peptides (25-mers) immobilized on cellulose membranes that scan the entire sequence of beta-arrestin 2, to define the interaction sites on beta arrestin 2 for binding of PDE4D5 and the cognate long isoform, PDE4D3. We have identified a binding site in the beta-arrestin 2 N-domain for the common PDE4D catalytic unit and two regions in the beta-arrestin 2 C-domain that confer specificity for PDE4D5 binding. Alanine-scanning peptide array analysis of the N domain binding region identified severely reduced interaction with PDE4D5 upon R26A substitution, and reduced interaction upon either K18A or T20A substitution. Similar analysis of the beta-arrestin 2 C-domain identified Arg286 and Asp291, together with the Leu215-His220 region, as being important for binding PDE4D5, but not PDE4D3. Transfection with wild-type beta-arrestin 2 profoundly decreased isoprenaline-stimulated PKA phosphorylation of the beta2-AR in MEFs (mouse embryo fibroblasts) lacking both beta-arrestin 1 and beta-arrestin 2. This effect was negated using either the R26A or the R286A mutant form of beta-arrestin 2 or a mutant with substitution of an alanine cassette for Leu215-His220, which showed little or no PDE4D5 binding, but was still recruited to the beta2-AR upon isoprenaline challenge. These data show that the interaction of PDE4D5 with both the N- and C-domains of beta-arrestin 2 are essential for beta2-AR regulation. PMID- 17288542 TI - Zebrafish kidney marrow contains ABCG2-dependent side population cells exhibiting hematopoietic stem cell properties. AB - Zebrafish (Danio rerio) has emerged as a powerful genetic model for the study of vertebrate hematopoiesis. However, methods for detection and isolation of hematopoietic stem cells (HSCs) have not yet been reported. In mammals, the combination of Hoechst 33342 staining with flow cytometry can be used for separation of a bone marrow side population (SP), which is highly enriched for HSCs. We applied a similar procedure to hematopoietic kidney marrow cells from adult zebrafish, and identified a segregated cohort of SP cells, which demonstrate a set of features typical of stem cells. SP cells show extremely low scatter characteristics, and are small in size with a minimum of cytoplasm. Treatment of zebrafish kidney marrow cells with reserpine or fumitremorgin C, which inhibit the ABCG2 transporter responsible for Hoechst 33342 efflux, caused a clear reduction in the number of SP cells. Consistent with the quiescent state of HSCs, the SP cells are strongly resistant to the myelosuppressive agent 5 fluorouracil. In addition, SP cells specifically demonstrate higher expression of genes known to be markers of HSCs of mammals. Hence, our results show that the SP phenotype is conserved between mammals and teleosts, and the properties of the zebrafish SP cells indicate a significant enrichment for HSCs. These rapid flow cytometric methods for purification of HSCs from zebrafish may greatly facilitate genetic analysis of stem cells using the advantages of this vertebrate model. PMID- 17288543 TI - Vitamin D regulates the phenotype of human breast cancer cells. AB - 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the most active vitamin D metabolite, regulates proliferation, survival, and differentiation in many cell types. 1,25(OH)(2)D(3) and several less calcemic analogs are in clinical trials against various neoplasias. We studied the effects of 1,25(OH)(2)D(3) on a panel of human breast cancer cells, which show similar vitamin D receptor (VDR) content but variable transcriptional and anti-proliferative responsiveness. In MDA-MB-453 cells, one of the responsive lines, 1,25(OH)(2)D(3) increased cell and nuclear size and induced a change from a rounded to a flattened morphology. By phase contrast, laser confocal and electron microscopy, we found that 1,25(OH)(2)D(3) changed the cytoarchitecture of actin filaments and microtubules and nuclear shape, induced filopodia and lamellipodia, and promoted cell-to-cell contacts via large cytoplasmic extensions. However, although claudin-7 and occludin content in the cells increased upon exposure to 1,25(OH)(2)D(3), these proteins were not located at the plasma membrane probably due to the absence of E-cadherin expression. Additionally, 1,25(OH)(2)D(3) induced the accumulation of alpha(v) integrin, beta(5)-integrin, focal adhesion kinase (FAK), and paxillin in focal adhesion plaques, concomitant with the increased phosphorylation of the FAK. 1,25(OH)(2)D(3) enhanced MDA-MB-453 and MDA-MB-468 cell adhesion to plastic but decreased adhesion to laminin. The expression of the mesenchymal marker N cadherin and of the myoepithelial marker P-cadherin was down-regulated by 1,25(OH)(2)D(3) in several breast cancer cell lines. Other myoepithelial proteins such as alpha(6)-integrin, beta(4)-integrin, and smooth muscle alpha-actin (SMA) were also repressed by 1,25(OH)(2)D(3) in MDA-MB-453 and MDA-MB-468 cells. Accordingly, mice lacking VDR (Vdr(-/-)) showed abnormally high levels of SMA and P-cadherin in their mammary gland. These findings show that 1,25(OH)(2)D(3) profoundly affects the phenotype of breast cancer cells, and suggest that it reverts the myoepithelial features associated with more aggressive forms and poor prognosis in human breast cancer. PMID- 17288544 TI - Expression profiling of the mouse prostate after castration and hormone replacement: implication of H-cadherin in prostate tumorigenesis. AB - Mice have been used extensively for studying normal prostate development and for generation of transgenic or knock-out prostate cancer animal models. To understand systematically and thoroughly the androgen responsive program in the mouse prostate, we carried out microarray analysis to profile gene expression changes during prostate involution and re-growth triggered by castration and subsequent hormone replacement. Genes with significant changes in these two processes were identified and gene ontology analyses revealed that they were mainly involved in response mechanisms, cell adhesion, metabolism, protein metabolism, and cell-cycle progression. The changes observed during prostate involution were largely reversed during re-growth. Sixty-four genes, including Nkx3.1 and probasin, and 65 other genes, including insulin-like growth factor binding protein 3 and H-cadherin (H-Cad), were further identified respectively as androgen-responsive genes and genes inversely correlated with androgen, based on their down- or up-regulation following castration and up- or down-regulation following androgen replacement. Potential androgen-responsive elements were found in the 5' upstream promoter region of 47 of those 65 genes, suggesting a potential suppression mechanism by androgen receptor. Of these, the role of H-Cad in tumorigenesis was further evaluated. Reduction of H-Cad transcript level was found in the majority of human prostate cancer cell lines and prostatic adenocarcinoma samples examined. Furthermore, induced H-Cad expression in DU145 cells, and knock-down of H-Cad expression in BPH1 cells inhibited and facilitated tumorigenicity, respectively. Taken together, our study provides a molecular understanding of the mouse prostate involution and re-growth processes and identifies a set of genes that are inversely correlated with androgen and may be potentially suppressive for tumorigenesis. PMID- 17288546 TI - Prions and prion diseases. PMID- 17288545 TI - Human placenta and bone marrow derived MSC cultured in serum-free, b-FGF containing medium express cell surface frizzled-9 and SSEA-4 and give rise to multilineage differentiation. AB - Conventionally, mesenchymal stem cells (MSC) are generated by plating cells from bone marrow (BM) or other sources into culture flasks and selecting plastic adherent cells with fibroblastoid morphology. These cells express CD9, CD10, CD13, CD73, CD105, CD166, and other markers but show only a weak or no expression of the embryonic markers stage-specific embryonic antigen-4 (SSEA-4), Oct-4 and nanog-3. Using a novel protocol we prepared MSC from BM and non-amniotic placenta (PL) by culture of Ficoll-selected cells in gelatin-coated flasks in the presence of a serum-free, basic fibroblast growth factor (b-FGF)-containing medium that was originally designed for the expansion of human embryonic stem cells (ESC). MSC generated in gelatin-coated flasks in the presence of ESC medium revealed a four-to fivefold higher proliferation rate than conventionally prepared MSC which were grown in uncoated flasks in serum-containing medium. In contrast, the colony forming unit fibroblast number was only 1.5- to twofold increased in PL-MSC and not affected in BM-MSC. PL-MSC grown in ESC medium showed an increased surface expression of SSEA-4 and frizzled-9 (FZD-9), an increased Oct-4 and nestin mRNA expression, and an induced expression of nanog-3. BM-MSC showed an induced expression of FZD-9, nanog-3, and Oct-4. In contrast to PL-MSC, only BM-MSC expressed the MSC-specific W8B2 antigen. When cultured under appropriate conditions, these MSC gave rise to functional adipocytes and osteoblast-like cells (mesoderm), glucagon and insulin expressing pancreatic-like cells (endoderm), as well as cells expressing the neuronal markers neuron-specific enolase, glutamic acid decarboxylase-67 (GAD), or class III beta-tubulin, and the astrocyte marker glial fibrillary acidic protein (ectoderm). In conclusion, using a novel protocol we demonstrate that adult BM-and neonatal PL-derived MSC can be induced to express high levels of FZD-9, Oct-4, nanog-3, and nestin and are able of multi-lineage differentiation. PMID- 17288547 TI - The reconstitution of mammalian prion infectivity de novo. AB - The discovery of prion disease transmission in mammals, as well as a non Mendelian type of inheritance in yeast, has led to the establishment of a new concept in biology, the prion hypothesis. The prion hypothesis postulates that an abnormal protein conformation propagates itself in an autocatalytic manner using the normal isoform of the same protein as a substrate and thereby acts either as a transmissible agent of disease (in mammals), or as a heritable determinant of phenotype (in yeast and fungus). While the prion biology of yeast and fungus supports this idea strongly, the direct proof of the prion hypothesis in mammals, specifically the reconstitution of the disease-associated isoform of the prion protein (PrP(Sc)) in vitro de novo from noninfectious prion protein, has been difficult to achieve despite many years of effort. The present review summarizes our current knowledge about the biochemical nature of the prion infectious agent and structure of PrP(Sc), describes potential strategies for generating prion infectivity de novo and provides some insight on why the reconstitution of infectivity has been difficult to achieve in vitro. Several hypotheses are proposed to explain the apparently low infectivity of the first generation of recently reported synthetic mammalian prions. PMID- 17288548 TI - The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies. AB - Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that are caused by unconventional pathogens and affect the central nervous system of animals and humans. Several different forms of these diseases result from natural infection (i.e. exposure to transmissible spongiform encephalopathy agents or prions, present in the natural environment of the respective host). This holds true also for scrapie in sheep, bovine spongiform encephalopathy in cattle, chronic wasting disease in elk and deer, or variant Creutzfeldt-Jakob disease in humans, all of which are assumed to originate predominantly from peroral prion infection. This article intends to provide an overview of the current state of knowledge on the spread of scrapie, chronic wasting disease, bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease agents through the body in naturally affected hosts, and in model animals experimentally challenged via the alimentary tract. Special attention is given to the tissue components and spreading pathways involved in the key stages of prion routing through the body, such as intestinal uptake, neuroinvasion of nerves and the central nervous system, and centrifugal spread from the brain and spinal cord to peripheral sites (e.g. sensory ganglia or muscles). The elucidation of the pathways and mechanisms by which prions invade a host and spread through the organism can contribute to efficient infection control strategies and the improvement of transmissible spongiform encephalopathy diagnostics. It may also help to identify prophylactic or therapeutic approaches that would impede naturally acquired transmissible spongiform encephalopathy infections. PMID- 17288549 TI - Molecular basis of cerebral neurodegeneration in prion diseases. AB - The biochemical nature and the replication of infectious prions have been intensively studied in recent years. Much less is known about the cellular events underlying neuronal dysfunction and cell death. As the cellular function of the normal cellular isoform of prion protein is not exactly known, the impact of gain of toxic function or loss of function, or a combination of both, in prion pathology is still controversial. There is increasing evidence that the normal cellular isoform of the prion protein is a key mediator in prion pathology. Transgenic models were instrumental in dissecting propagation of prions, disease associated isoforms of prion protein and amyloid production, and induction of neurodegeneration. Four experimental avenues will be discussed here which address scenarios of inappropriate trafficking, folding, or targeting of the prion protein. PMID- 17288551 TI - ER stress and diseases. AB - Proteins synthesized in the endoplasmic reticulum (ER) are properly folded with the assistance of ER chaperones. Malfolded proteins are disposed of by ER associated protein degradation (ERAD). When the amount of unfolded protein exceeds the folding capacity of the ER, human cells activate a defense mechanism called the ER stress response, which induces expression of ER chaperones and ERAD components and transiently attenuates protein synthesis to decrease the burden on the ER. It has been revealed that three independent response pathways separately regulate induction of the expression of chaperones, ERAD components, and translational attenuation. A malfunction of the ER stress response caused by aging, genetic mutations, or environmental factors can result in various diseases such as diabetes, inflammation, and neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and bipolar disorder, which are collectively known as 'conformational diseases'. In this review, I will summarize recent progress in this field. Molecules that regulate the ER stress response would be potential candidates for drug targets in various conformational diseases. PMID- 17288550 TI - The bile/arsenite/riboflavin transporter (BART) superfamily. AB - Secondary transmembrane transport carriers fall into families and superfamilies allowing prediction of structure and function. Here we describe hundreds of sequenced homologues that belong to six families within a novel superfamily, the bile/arsenite/riboflavin transporter (BART) superfamily, of transport systems and putative signalling proteins. Functional data for members of three of these families are available, and they transport bile salts and other organic anions, the bile acid:Na(+) symporter (BASS) family, inorganic anions such as arsenite and antimonite, the arsenical resistance-3 (Acr3) family, and the riboflavin transporter (RFT) family. The first two of these families, as well as one more family with no functionally characterized members, exhibit a probable 10 transmembrane spanner (TMS) topology that arose from a tandemly duplicated 5 TMS unit. Members of the RFT family have a 5 TMS topology, and are homologous to each of the repeat units in the 10 TMS proteins. The other two families [sensor histidine kinase (SHK) and kinase/phosphatase/synthetase/hydrolase (KPSH)] have a single 5 TMS unit preceded by an N-terminal TMS and followed by a hydrophilic sensor histidine kinase domain (the SHK family) or catalytic domains resembling sensor kinase, phosphatase, cyclic di-GMP synthetase and cyclic di-GMP hydrolase catalytic domains, as well as various noncatalytic domains (the KPSH family). Because functional data are not available for members of the SHK and KPSH families, it is not known if the transporter domains retain transport activity or have evolved exclusive functions in molecular reception and signal transmission. This report presents characteristics of a unique protein superfamily and provides guides for future studies concerning structural, functional and mechanistic properties of its constituent members. PMID- 17288552 TI - Modulation of Ca2+ entry and plasma membrane potential by human TRPM4b. AB - TRPM4b is a Ca(2+)-activated, voltage-dependent monovalent cation channel that has been shown to act as a negative regulator of Ca(2+) entry and to be involved in the generation of oscillations of Ca(2+) influx in Jurkat T-lymphocytes. Transient overexpression of TRPM4b as an enhanced green fluorescence fusion protein in human embryonic kidney (HEK) cells resulted in its localization in the plasma membrane, as demonstrated by confocal fluorescence microscopy. The functionality and plasma membrane localization of overexpressed TRPM4b was confirmed by induction of Ca(2+)-dependent inward and outward currents in whole cell patch clamp recordings. HEK-293 cells stably overexpressing TRPM4b showed higher ionomycin-activated Ca(2+) influx than wild-type cells. In addition, analysis of the membrane potential using the potentiometric dye bis-(1,3 dibutylbarbituric acid)-trimethine oxonol and by current clamp experiments in the perforated patch configuration revealed a faster initial depolarization after activation of Ca(2+) entry with ionomycin. Furthermore, TRPM4b expression facilitated repolarization and thereby enhanced sustained Ca(2+) influx. In conclusion, in cells with a small negative membrane potential, such as HEK-293 cells, TRPM4b acts as a positive regulator of Ca(2+) entry. PMID- 17288553 TI - Structural studies of thymidine kinases from Bacillus anthracis and Bacillus cereus provide insights into quaternary structure and conformational changes upon substrate binding. AB - Thymidine kinase (TK) is the key enzyme in salvaging thymidine to produce thymidine monophosphate. Owing to its ability to phosphorylate nucleoside analogue prodrugs, TK has gained attention as a rate-limiting drug activator. We describe the structures of two bacterial TKs, one from the pathogen Bacillus anthracis in complex with the substrate dT, and the second from the food-poison associated Bacillus cereus in complex with the feedback inhibitor dTTP. Interestingly, in contrast with previous structures of TK in complex with dTTP, in this study dTTP occupies the phosphate donor site and not the phosphate acceptor site. This results in several conformational changes compared with TK structures described previously. One of the differences is the way tetramers are formed. Unlike B. anthracis TK, B. cereus TK shows a loose tetramer. Moreover, the lasso-domain is in open conformation in B. cereus TK without any substrate in the active site, whereas in B. anthracis TK the loop conformation is closed and thymidine occupies the active site. Another conformational difference lies within a region of 20 residues that we refer to as phosphate-binding beta-hairpin. The phosphate-binding beta-hairpin seems to be a flexible region of the enzyme which becomes ordered upon formation of hydrogen bonds to the alpha-phosphate of the phosphate donor, dTTP. In addition to descriptions of the different conformations that TK may adopt during the course of reaction, the oligomeric state of the enzyme is investigated. PMID- 17288554 TI - Crystal structure and solution characterization of the activation domain of human methionine synthase. AB - Human methionine synthase (hMS) is a multidomain cobalamin-dependent enzyme that catalyses the conversion of homocysteine to methionine by methyl group transfer. We report here the 1.6 A crystal structure of the C-terminal activation domain of hMS. The structure is C-shaped with the core comprising mixed alpha and beta regions, dominated by a twisted antiparallel beta sheet with a beta-meander region. These features, including the positions of the active-site residues, are similar to the activation domain of Escherichia coli cobalamin-dependent MS (MetH). Structural and solution studies suggest a small proportion of hMS activation domain exists in a dimeric form, which contrasts with the monomeric form of the E. coli homologue. Fluorescence studies show that human activation domain interacts with the FMN-binding domain of human methionine synthase reductase (hMSR). This interaction is enhanced in the presence of S-adenosyl methionine. Binding of the D963E/K1071N mutant activation domain to the FMN domain of MSR is weaker than with wild-type activation domain. This suggests that one or both of the residues D963 and K1071 are important in partner binding. Key differences in the sequences and structures of hMS and MetH activation domains are recognized and include a major reorientation of an extended 3(10)-containing loop in the human protein. This structural alteration might reflect differences in their respective reactivation complexes and/or potential for dimer formation. The reported structure is a component of the multidomain hMS : MSR complex, and represents an important step in understanding the impact of clinical mutations and polymorphisms in this key electron transfer complex. PMID- 17288555 TI - Activity of the plant peptide aglycin in mammalian systems. AB - A 37 residue peptide, aglycin, has been purified from porcine intestine. The sequence is identical to that of residues 27-63 of plant albumin 1 B precursor (PA1B, chain b) from pea seeds. Aglycin resists in vitro proteolysis by pepsin, trypsin and Glu-C protease, compatible with its intestinal occurrence and an exogenous origin from plant food. When subcutaneously injected into mice (at 10 microg.g(-1) body weight), aglycin has a hyperglycemic effect resulting in a doubling of the blood glucose level within 60 min. Using surface plasmon resonance biosensor technology, an aglycin binding protein with an apparent molecular mass of 34 kDa was detected in membrane protein extracts from porcine and mice pancreas. The polypeptide was purified by affinity chromatography and identified through peptide mass fingerprinting as the voltage-dependent anion selective channel protein 1. The results indicate that aglycin has the potential to interfere with mammalian physiology. PMID- 17288556 TI - TRPV1 at nerve endings regulates growth cone morphology and movement through cytoskeleton reorganization. AB - While the importance of Ca(2+) channel activity in axonal path finding is established, the underlying mechanisms are not clear. Here, we show that transient receptor potential vanilloid receptor 1 (TRPV1), a member of the TRP superfamily of nonspecific ion channels, is physically and functionally present at dynamic neuronal extensions, including growth cones. These nonselective cation channels sense exogenous ligands, such as resenifera toxin, and endogenous ligands, such as N-arachidonoyl-dopamine (NADA), and affect the integrity of microtubule cytoskeleton. Using TRPV1-transiently transfected F11 cells and embryonic dorsal root ganglia explants, we show that activation of TRPV1 results in growth cone retraction, and collapse and formation of varicosities along neurites. These changes were due to TRPV1-activation-mediated disassembly of microtubules and are partly Ca(2+)-independent. Prolonged activation with very low doses (1 nM) of NADA results in shortening of neurites in the majority of isolectin B4-positive dorsal root ganglia neurones. We postulate that TRPV1 activation plays an inhibitory role in sensory neuronal extension and motility by regulating the disassembly of microtubules. This might have a role in the chronification of pain. PMID- 17288557 TI - PACSIN 1 forms tetramers via its N-terminal F-BAR domain. AB - The ability of protein kinase C and casein kinase 2 substrate in neurons (PACSIN)/syndapin proteins to self-polymerize is crucial for the simultaneous interactions with more than one Src homology 3 domain-binding partner or with lipid membranes. The assembly of this network has profound effects on the neural Wiskott-Aldrich syndrome protein-mediated attachment of the actin polymerization machinery to vesicle membranes as well as on the movement of the corresponding vesicles. Also, the sensing of vesicle membranes and/or the induction of membrane curvature are more easily facilitated in the presence of larger PACSIN complexes. The N-terminal Fes-CIP homology and Bin-Amphiphysin-Rvs (F-BAR) domains of several PACSIN-related proteins have been shown to mediate self-interactions, whereas studies using deletion mutants derived from closely related proteins led to the view that oligomerization depends on the formation of a trimeric complex via a coiled-coil region present in these molecules. To address whether the model of trimeric complex formation is applicable to PACSIN 1, the protein was recombinantly expressed and tested in four different assays for homologous interactions. The results showed that PACSIN 1 forms tetramers of about 240 kDa, with the self-interaction having a K(D) of 6.4 x 10(-8) M. Ultrastructural analysis of these oligomers after negative staining showed that laterally arranged PACSIN molecules bind to each other via a large globular domain and form a barrel-like structure. Together, these results demonstrate that the N-terminal F-BAR domain of PACSIN 1 forms the contact site for a tetrameric structure, which is able to simultaneously interact with multiple Src homology 3 binding partners. PMID- 17288558 TI - Fast set-up of doxycycline-inducible protein expression in human cell lines with a single plasmid based on Epstein-Barr virus replication and the simple tetracycline repressor. AB - We have developed a novel plasmid vector, pEBTetD, for full establishment of doxycycline-inducible protein expression by just a single transfection. pEBTetD contains an Epstein-Barr virus origin of replication for stable and efficient episomal propagation in human cell lines, a cassette for continuous expression of the simple tetracycline repressor, and a cytomegalovirus-type 2 tetracycline operator (tetO2)-tetO2 promoter. As there is no integration of vector into the genome, clonal isolation of transfected cells is not necessary. Cells are thus ready for use 1 week after transfection; this contrasts with 3-12 weeks for other systems. Adequate regulation of protein expression was accomplished by abrogation of mRNA polyadenylation. In northern analysis of seven cDNAs coding for transport proteins, pools of transfected human embryonic kidney 293 cells showed on/off mRNA ratios in the order of 100:1. Cell pools were also analyzed for regulation of protein function. With two transport proteins of the plasma membrane, the on/off activity ratios were 24:1 and 34:1, respectively. With enhanced green fluorescent protein, a 23:1 ratio was observed based on fluorescence intensity data from flow cytometry. The unique advantage of our system rests on the unmodified tetracycline repressor, which is less likely, by relocation upon binding of doxycycline, to cause cellular disturbances than chimera of tetracycline repressor and eukaryotic transactivation domains. Thus, in a comprehensive comparison of on- and off-states, a steady cellular background is provided. Finally, in contrast to a system based on Flp recombinase, the set-up of our system is inherently reliable. PMID- 17288559 TI - Proteomics of Synechocystis sp. PCC 6803. Identification of novel integral plasma membrane proteins. AB - The cyanobacterial plasma membrane is an essential cell barrier with functions such as the control of taxis, nutrient uptake and secretion. These functions are carried out by integral membrane proteins, which are difficult to identify using standard proteomic methods. In this study, integral proteins were enriched from purified plasma membranes of Synechocystis sp. PCC 6803 using urea wash followed by protein resolution in 1D SDS/PAGE. In total, 51 proteins were identified by peptide mass fingerprinting using MALDI-TOF MS. More than half of the proteins were predicted to be integral with 1-12 transmembrane helices. The majority of the proteins had not been identified previously, and include members of metalloproteases, chemotaxis proteins, secretion proteins, as well as type 2 NAD(P)H dehydrogenase and glycosyltransferase. The obtained results serve as a useful reference for further investigations of the address codes for targeting of integral membrane proteins in cyanobacteria. PMID- 17288560 TI - Geranylgeranyl reductase involved in the biosynthesis of archaeal membrane lipids in the hyperthermophilic archaeon Archaeoglobus fulgidus. AB - Complete saturation of the geranylgeranyl groups of biosynthetic intermediates of archaeal membrane lipids is an important reaction that confers chemical stability on the lipids of archaea, which generally inhabit extreme conditions. An enzyme encoded by the AF0464 gene of a hyperthermophilic archaeon, Archaeoglobus fulgidus, which is a distant homologue of plant geranylgeranyl reductases and an A. fulgidus menaquinone-specific prenyl reductase [Hemmi H, Yoshihiro T, Shibuya K, Nakayama T, & Nishino T (2005) J Bacteriol187, 1937-1944], was recombinantly expressed and purified, and its geranylgeranyl reductase activity was examined. The radio HPLC analysis indicated that the flavoenzyme, which binds FAD noncovalently, showed activity towards lipid-biosynthetic intermediates containing one or two geranylgeranyl groups under anaerobic conditions. It showed a preference for 2,3-di-O-geranylgeranylglyceryl phosphate over 3-O geranylgeranylglyceryl phosphate and geranylgeranyl diphosphate in vitro, and did not reduce the prenyl group of respiratory quinones in Escherichia coli cells. The substrate specificity strongly suggests that the enzyme is involved in the biosynthesis of archaeal membrane lipids. GC-MS analysis of the reaction product from 2,3-di-O-geranylgeranylglyceryl phosphate proved that the substrate was converted to archaetidic acid (2,3-di-O-phytanylglyceryl phosphate). The archaeal enzyme required sodium dithionite as the electron donor for activity in vitro, similarly to the menaquinone-specific prenyl reductase from the same anaerobic archaeon. On the other hand, in the presence of NADPH (the preferred electron donor for plant homologues), the enzyme reaction did not proceed. PMID- 17288561 TI - Green fluorescent protein-tagging reduces the nucleocytoplasmic shuttling specifically of unphosphorylated STAT1. AB - Fluorescence recovery after photobleaching (FRAP) and related techniques using green fluorescent protein (GFP)-tagged proteins are widely used to study the subcellular trafficking of proteins. It was concluded from these experiments that the cytokine-induced nuclear import of tyrosine-phosphorylated (activated) signal transducer and activator of transcription 1 (STAT1) was rapid, while the constitutive shuttling of unphosphorylated STAT1 was determined to be inefficient. However, unrelated experiments came to different conclusions concerning the constitutive translocation of STAT1. Because these discrepancies have not been resolved, it remained unclear whether or not unphosphorylated STAT1 is a relevant regulator of cytokine-dependent gene expression. This study was initiated to examine the influence of GFP-tagging on the nucleocytoplasmic shuttling of phosphorylated and unphosphorylated STAT1. In accordance with previous findings our results confirm the undisturbed rapid nuclear import of GFP tagged activated STAT1. However, we reveal an inhibitory influence of GFP specifically on the constitutive nucleocytoplasmic cycling of the unphosphorylated protein. The decreased shuttling of unphosphorylated STAT1-GFP significantly reduced the activation level while nuclear accumulation was prolonged. Importantly, despite unimpaired nuclear import of activated STAT1 the transcription of a STAT1-dependent reporter gene was more than halved after GFP tagging, which could be linked directly to reduced nucleocytoplasmic shuttling. In conclusion, it is demonstrated that GFP-based techniques considerably underestimate the actual shuttling rate of unphosphorylated native STAT1. The results confirm that the activation of STAT1 and hence its transcriptional activity is proportional to the nucleocytoplasmic shuttling rate of the unphosphorylated protein. Moreover, our data indicate that GFP-tagging may differently affect the mechanistically distinct translocation pathways of a shuttling protein. PMID- 17288562 TI - Tissue expression and biochemical characterization of human 2-amino 3 carboxymuconate 6-semialdehyde decarboxylase, a key enzyme in tryptophan catabolism. AB - 2-amino 3-carboxymuconate 6-semialdehyde decarboxylase (ACMSD, EC 4.1.1.45) plays a key role in tryptophan catabolism. By diverting 2-amino 3-carboxymuconate semialdehyde from quinolinate production, the enzyme regulates NAD biosynthesis from the amino acid, directly affecting quinolinate and picolinate formation. ACMSD is therefore an attractive therapeutic target for treating disorders associated with increased levels of tryptophan metabolites. Through an isoform specific real-time PCR assay, the constitutive expression of two alternatively spliced ACMSD transcripts (ACMSD I and II) has been examined in human brain, liver and kidney. Both transcripts are present in kidney and liver, with highest expression occurring in kidney. In brain, no ACMSD II expression is detected, and ACMSD I is present at very low levels. Cloning of the two cDNAs in yeast expression vectors and production of the recombinant proteins, revealed that only ACMSD I is endowed with enzymatic activity. After purification to homogeneity, this enzyme was found to be a monomer, with a broad pH optimum ranging from 6.5 to 8.0, a K(m) of 6.5 microM, and a k(cat) of 1.0 s(-1). ACMSD I is inhibited by quinolinic acid, picolinic acid and kynurenic acid, and it is activated slightly by Fe(2+) and Co(2+). Site-directed mutagenesis experiments confirmed the catalytic role of residues, conserved in all ACMSDs so far characterized, which in the bacterial enzyme participate directly in the metallocofactor binding. Even so, the properties of the human enzyme differ significantly from those reported for the bacterial counterpart, suggesting that the metallocofactor is buried deep within the protein and not as accessible as it is in bacterial ACMSD. PMID- 17288563 TI - Direct identification of hydrophobins and their processing in Trichoderma using intact-cell MALDI-TOF MS. AB - Intact-cell MS (ICMS) was applied for the direct detection of hydrophobins in various species and strains of Hypocrea/Trichoderma. In both mycelia and spores, dominating peaks were identified as hydrophobins by detecting mass shifts of 8 Da of reduced and unreduced forms, the analysis of knockout mutants, and comparison with protein databases. Strain-specific processing was observed in the case of Hypocrea jecorina (anamorph Trichoderma reesei). An analysis of 32 strains comprising 29 different species of Trichoderma and Hypocrea showed hydrophobin patterns that were specific at both at the species and isolate (subspecies) levels. The method therefore permits rapid and direct detection of hydrophobin class II compositions and may also provide a means to identify Trichoderma (and other fungal) species and strains from microgram amounts of biomass without prior cultivation. PMID- 17288564 TI - Molecular characterization of the membrane-bound quinol peroxidase functionally connected to the respiratory chain. AB - Here, we report for the first time quinol peroxidase (QPO), an enzyme that uses ubiquinol-1 as an electron donor for the reduction of H(2)O(2) to water. We purified QPO to > 90% purity from the membrane fraction of Actinobacillus actinomycetemcomitans. QPO is a 53.6-kDa protein that contains three heme c molecules. The qpo gene was predicted to encode a putative bacterial cytochrome c peroxidase with N-terminal extensions containing an additional potential heme c binding motif. Although qpo has high sequence homology to bacterial cytochrome c peroxidases, QPO did not catalyze peroxidation in the presence of horse heart cytochrome c. In addition, the cytoplasmic membrane of A. actinomycetemcomitans had apparent QPO-dependent peroxidase activity in the presence of NADH or succinate, which are substrates for the respiratory chain. Based on these findings, we present a new mechanism for the scavenging of reactive oxygen species in which quinol in the respiratory chain is consumed. PMID- 17288565 TI - Regulation of tristetraprolin during differentiation of 3T3-L1 preadipocytes. AB - Tristetraprolin is a zinc-finger-containing RNA-binding protein. Tristetraprolin binds to AU-rich elements of target mRNAs such as proto-oncogenes, cytokines and growth factors, and then induces mRNA rapid degradation. It was observed as an immediate-early gene that was induced in response to several kinds of stimulus, such as insulin and other growth factors and stimulators of innate immunity such as lipopolysaccharides. We observed that tristetraprolin was briefly expressed during a 1-8 h period after induction of differentiation in 3T3-L1 preadipocytes. Detailed analysis showed that tristetraprolin mRNA expression was stimulated by fetal bovine serum and differentiation inducers, and was followed by rapid degradation. The 3'UTR of tristetraprolin mRNAs contain adenine- and uridine-rich elements. Biochemical analyses using RNA pull-down, RNA immunoprecipitation and gel shift experiments demonstrated that adenine- and uridine-rich element-binding proteins, HuR and tristetraprolin itself, were associated with tristetraprolin adenine- and uridine-rich elements. Functional characterization confirmed that tristetraprolin negatively regulated its own expression. Thus, our results indicated that the tight autoregulation of tristetraprolin expression correlated with its critical functional role in 3T3-L1 differentiation. PMID- 17288567 TI - Proceedings of the First International Conference on Phylogenomics. March 15-19, 2006. Quebec, Canada. PMID- 17288568 TI - Identifying dramatic selection shifts in phylogenetic trees. AB - BACKGROUND: The rate of evolution varies spatially along genomes and temporally in time. The presence of evolutionary rate variation is an informative signal that often marks functional regions of genomes and historical selection events. There exist many tests for temporal rate variation, or heterotachy, that start by partitioning sampled sequences into two or more groups and testing rate homogeneity among the groups. I develop a Bayesian method to infer phylogenetic trees with a divergence point, or dramatic temporal shifts in selection pressure that affect many nucleotide sites simultaneously, located at an unknown position in the tree. RESULTS: Simulation demonstrates that the method is most able to detect divergence points when rate variation and the number of affected sites is high, but not beyond biologically relevant values. The method is applied to two viral data sets. A divergence point is identified separating the B and C subtypes, two genetically distinct variants of HIV that have spread into different human populations with the AIDS epidemic. In contrast, no strong signal of temporal rate variation is found in a sample of F and H genotypes, two genetic variants of HBV that have likely evolved with humans during their immigration and expansion into the Americas. CONCLUSION: Temporal shifts in evolutionary rate of sufficient magnitude are detectable in the history of sampled sequences. The ability to detect such divergence points without the need to specify a prior hypothesis about the location or timing of the divergence point should help scientists identify historically important selection events and decipher mechanisms of evolution. PMID- 17288569 TI - Long-wavelength sensitive visual pigments of the guppy (Poecilia reticulata): six opsins expressed in a single individual. AB - BACKGROUND: The diversity of visual systems in fish has long been of interest for evolutionary biologists and neurophysiologists, and has recently begun to attract the attention of molecular evolutionary geneticists. Several recent studies on the copy number and genomic organization of visual pigment proteins, the opsins, have revealed an increased opsin diversity in fish relative to most vertebrates, brought about through recent instances of opsin duplication and divergence. However, for the subfamily of opsin genes that mediate vision at the long wavelength end of the spectrum, the LWS opsins, it appears that most fishes possess only one or two loci, a value comparable to most other vertebrates. Here, we characterize the LWS opsins from cDNA of an individual guppy, Poecilia reticulata, a fish that is known exhibit variation in its long-wavelength sensitive visual system, mate preferences and colour patterns. RESULTS: We identified six LWS opsins expressed within a single individual. Phylogenetic analysis revealed that these opsins descend from duplication events both pre dating and following the divergence of the guppy lineage from that of the bluefin killifish, Lucania goodei, the closest species for which comparable data exists. Numerous amino acid substitutions exist among these different LWS opsins, many at sites known to be important for visual pigment function, including spectral sensitivity and G-protein activation. Likelihood analyses using codon-based models of evolution reveal significant changes in selective constraint along two of the guppy LWS opsin lineages. CONCLUSION: The guppy displays an unusually high number of LWS opsins compared to other fish, and to vertebrates in general. Observing both substitutions at functionally important sites and the persistence of lineages across species boundaries suggests that these opsins might have functionally different roles, especially with regard to G-protein activation. The reasons why are currently unknown, but may relate to aspects of the guppy's behavioural ecology, in which both male colour patterns and the female mate preferences for these colour patterns experience strong, highly variable selection pressures. PMID- 17288570 TI - FlowerPower: clustering proteins into domain architecture classes for phylogenomic inference of protein function. AB - BACKGROUND: Function prediction by transfer of annotation from the top database hit in a homology search has been shown to be prone to systematic error. Phylogenomic analysis reduces these errors by inferring protein function within the evolutionary context of the entire family. However, accuracy of function prediction for multi-domain proteins depends on all members having the same overall domain structure. By contrast, most common homolog detection methods are optimized for retrieving local homologs, and do not address this requirement. RESULTS: We present FlowerPower, a novel clustering algorithm designed for the identification of global homologs as a precursor to structural phylogenomic analysis. Similar to methods such as PSIBLAST, FlowerPower employs an iterative approach to clustering sequences. However, rather than using a single HMM or profile to expand the cluster, FlowerPower identifies subfamilies using the SCI PHY algorithm and then selects and aligns new homologs using subfamily hidden Markov models. FlowerPower is shown to outperform BLAST, PSI-BLAST and the UCSC SAM-Target 2K methods at discrimination between proteins in the same domain architecture class and those having different overall domain structures. CONCLUSION: Structural phylogenomic analysis enables biologists to avoid the systematic errors associated with annotation transfer; clustering sequences based on sharing the same domain architecture is a critical first step in this process. FlowerPower is shown to consistently identify homologous sequences having the same domain architecture as the query. AVAILABILITY: FlowerPower is available as a webserver at http://phylogenomics.berkeley.edu/flowerpower/. PMID- 17288571 TI - RNase MRP and the RNA processing cascade in the eukaryotic ancestor. AB - BACKGROUND: Within eukaryotes there is a complex cascade of RNA-based macromolecules that process other RNA molecules, especially mRNA, tRNA and rRNA. An example is RNase MRP processing ribosomal RNA (rRNA) in ribosome biogenesis. One hypothesis is that this complexity was present early in eukaryotic evolution; an alternative is that an initial simpler network later gained complexity by gene duplication in lineages that led to animals, fungi and plants. Recently there has been a rapid increase in support for the complexity-early theory because the vast majority of these RNA-processing reactions are found throughout eukaryotes, and thus were likely to be present in the last common ancestor of living eukaryotes, herein called the Eukaryotic Ancestor. RESULTS: We present an overview of the RNA processing cascade in the Eukaryotic Ancestor and investigate in particular, RNase MRP which was previously thought to have evolved later in eukaryotes due to its apparent limited distribution in fungi and animals and plants. Recent publications, as well as our own genomic searches, find previously unknown RNase MRP RNAs, indicating that RNase MRP has a wide distribution in eukaryotes. Combining secondary structure and promoter region analysis of RNAs for RNase MRP, along with analysis of the target substrate (rRNA), allows us to discuss this distribution in the light of eukaryotic evolution. CONCLUSION: We conclude that RNase MRP can now be placed in the RNA-processing cascade of the Eukaryotic Ancestor, highlighting the complexity of RNA-processing in early eukaryotes. Promoter analyses of MRP-RNA suggest that regulation of the critical processes of rRNA cleavage can vary, showing that even these key cellular processes (for which we expect high conservation) show some species-specific variability. We present our consensus MRP-RNA secondary structure as a useful model for further searches. PMID- 17288572 TI - Comparative analysis of genome tiling array data reveals many novel primate specific functional RNAs in human. AB - BACKGROUND: Widespread transcription activities in the human genome were recently observed in high-resolution tiling array experiments, which revealed many novel transcripts that are outside of the boundaries of known protein or RNA genes. Termed as "TARs" (Transcriptionally Active Regions), these novel transcribed regions represent "dark matter" in the genome, and their origin and functionality need to be explained. Many of these transcripts are thought to code for novel proteins or non-protein-coding RNAs. We have applied an integrated bioinformatics approach to investigate the properties of these TARs, including cross-species conservation, and the ability to form stable secondary structures. The goal of this study is to identify a list of potential candidate sequences that are likely to code for functional non-protein-coding RNAs. We are particularly interested in the discovery of those functional RNA candidates that are primate-specific, i.e. those that do not have homologs in the mouse or dog genomes but in rhesus. RESULTS: Using sequence conservation and the probability of forming stable secondary structures, we have identified approximately 300 possible candidates for primate-specific noncoding RNAs. We are currently in the process of sequencing the orthologous regions of these candidate sequences in several other primate species. We will then be able to apply a "phylogenetic shadowing" approach to analyze the functionality of these ncRNA candidates. CONCLUSION: The existence of potential primate-specific functional transcripts has demonstrated the limitation of previous genome comparison studies, which put too much emphasis on conservation between human and rodents. It also argues for the necessity of sequencing additional primate species to gain a better and more comprehensive understanding of the human genome. PMID- 17288573 TI - Evolution of motif variants and positional bias of the cyclic-AMP response element. AB - BACKGROUND: Transcription factors regulate gene expression by interacting with their specific DNA binding sites. Some transcription factors, particularly those involved in transcription initiation, always bind close to transcription start sites (TSS). Others have no such preference and are functional on sites even tens of thousands of base pairs (bp) away from the TSS. The Cyclic-AMP response element (CRE) binding protein (CREB) binds preferentially to a palindromic sequence (TGACGTCA), known as the canonical CRE, and also to other CRE variants. CREB can activate transcription at CREs thousands of bp away from the TSS, but in mammals CREs are found far more frequently within 1 to 150 bp upstream of the TSS than in any other region. This property is termed positional bias. The strength of CREB binding to DNA is dependent on the sequence of the CRE motif. The central CpG dinucleotide in the canonical CRE (TGACGTCA) is critical for strong binding of CREB dimers. Methylation of the cytosine in the CpG can inhibit binding of CREB. Deamination of the methylated cytosines causes a C to T transition, resulting in a functional, but lower affinity CRE variant, TGATGTCA. RESULTS: We performed genome-wide surveys of CREs in a number of species (from worm to human) and showed that only vertebrates exhibited a CRE positional bias. We performed pair-wise comparisons of human CREs with orthologous sequences in mouse, rat and dog genomes and found that canonical and TGATGTCA variant CREs are highly conserved in mammals. However, when orthologous sequences differ, canonical CREs in human are most frequently TGATGTCA in the other species and vice-versa. We have identified 207 human CREs showing such differences. CONCLUSION: Our data suggest that the positional bias of CREs likely evolved after the separation of urochordata and vertebrata. Although many canonical CREs are conserved among mammals, there are a number of orthologous genes that have canonical CREs in one species but the TGATGTCA variant in another. These differences are likely due to deamination of the methylated cytosines in the CpG and may contribute to differential transcriptional regulation among orthologous genes. PMID- 17288574 TI - Assembly rules for protein networks derived from phylogenetic-statistical analysis of whole genomes. AB - BACKGROUND: We report an analysis of a protein network of functionally linked proteins, identified from a phylogenetic statistical analysis of complete eukaryotic genomes. Phylogenetic methods identify pairs of proteins that co evolve on a phylogenetic tree, and have been shown to have a high probability of correctly identifying known functional links. RESULTS: The eukaryotic correlated evolution network we derive displays the familiar power law scaling of connectivity. We introduce the use of explicit phylogenetic methods to reconstruct the ancestral presence or absence of proteins at the interior nodes of a phylogeny of eukaryote species. We find that the connectivity distribution of proteins at the point they arise on the tree and join the network follows a power law, as does the connectivity distribution of proteins at the time they are lost from the network. Proteins resident in the network acquire connections over time, but we find no evidence that 'preferential attachment'--the phenomenon of newly acquired connections in the network being more likely to be made to proteins with large numbers of connections--influences the network structure. We derive a 'variable rate of attachment' model in which proteins vary in their propensity to form network interactions independently of how many connections they have or of the total number of connections in the network, and show how this model can produce apparent power-law scaling without preferential attachment. CONCLUSION: A few simple rules can explain the topological structure and evolutionary changes to protein-interaction networks: most change is concentrated in satellite proteins of low connectivity and small phenotypic effect, and proteins differ in their propensity to form attachments. Given these rules of assembly, power law scaled networks naturally emerge from simple principles of selection, yielding protein interaction networks that retain a high-degree of robustness on short time scales and evolvability on longer evolutionary time scales. PMID- 17288575 TI - SCaFoS: a tool for selection, concatenation and fusion of sequences for phylogenomics. AB - BACKGROUND: Phylogenetic analyses based on datasets rich in both genes and species (phylogenomics) are becoming a standard approach to resolve evolutionary questions. However, several difficulties are associated with the assembly of large datasets, such as multiple copies of a gene per species (paralogous or xenologous genes), lack of some genes for a given species, or partial sequences. The use of undetected paralogous or xenologous genes in phylogenetic inference can lead to inaccurate results, and the use of partial sequences to a lack of resolution. A tool that selects sequences, species, and genes, while dealing with these issues, is needed in a phylogenomics context. RESULTS: Here, we present SCaFoS, a tool that quickly assembles phylogenomic datasets containing maximal phylogenetic information while adjusting the amount of missing data in the selection of species, sequences and genes. Starting from individual sequence alignments, and using monophyletic groups defined by the user, SCaFoS creates chimeras with partial sequences, or selects, among multiple sequences, the orthologous and/or slowest evolving sequences. Once sequences representing each predefined monophyletic group have been selected, SCaFos retains genes according to the user's allowed level of missing data and generates files for super-matrix and super-tree analyses in several formats compatible with standard phylogenetic inference software. Because no clear-cut criteria exist for the sequence selection, a semi-automatic mode is available to accommodate user's expertise. CONCLUSION: SCaFos is able to deal with datasets of hundreds of species and genes, both at the amino acid or nucleotide level. It has a graphical interface and can be integrated in an automatic workflow. Moreover, SCaFoS is the first tool that integrates user's knowledge to select orthologous sequences, creates chimerical sequences to reduce missing data and selects genes according to their level of missing data. Finally, applying SCaFoS to different datasets, we show that the judicious selection of genes, species and sequences reduces tree reconstruction artefacts, especially if the dataset includes fast evolving species. PMID- 17288576 TI - Inferring angiosperm phylogeny from EST data with widespread gene duplication. AB - BACKGROUND: Most studies inferring species phylogenies use sequences from single copy genes or sets of orthologs culled from gene families. For taxa such as plants, with very high levels of gene duplication in their nuclear genomes, this has limited the exploitation of nuclear sequences for phylogenetic studies, such as those available in large EST libraries. One rarely used method of inference, gene tree parsimony, can infer species trees from gene families undergoing duplication and loss, but its performance has not been evaluated at a phylogenomic scale for EST data in plants. RESULTS: A gene tree parsimony analysis based on EST data was undertaken for six angiosperm model species and Pinus, an outgroup. Although a large fraction of the tentative consensus sequences obtained from the TIGR database of ESTs was assembled into homologous clusters too small to be phylogenetically informative, some 557 clusters contained promising levels of information. Based on maximum likelihood estimates of the gene trees obtained from these clusters, gene tree parsimony correctly inferred the accepted species tree with strong statistical support. A slight variant of this species tree was obtained when maximum parsimony was used to infer the individual gene trees instead. CONCLUSION: Despite the complexity of the EST data and the relatively small fraction eventually used in inferring a species tree, the gene tree parsimony method performed well in the face of very high apparent rates of duplication. PMID- 17288577 TI - Suppression of long-branch attraction artefacts in the animal phylogeny using a site-heterogeneous model. AB - BACKGROUND: Thanks to the large amount of signal contained in genome-wide sequence alignments, phylogenomic analyses are converging towards highly supported trees. However, high statistical support does not imply that the tree is accurate. Systematic errors, such as the Long Branch Attraction (LBA) artefact, can be misleading, in particular when the taxon sampling is poor, or the outgroup is distant. In an otherwise consistent probabilistic framework, systematic errors in genome-wide analyses can be traced back to model mis specification problems, which suggests that better models of sequence evolution should be devised, that would be more robust to tree reconstruction artefacts, even under the most challenging conditions. METHODS: We focus on a well characterized LBA artefact analyzed in a previous phylogenomic study of the metazoan tree, in which two fast-evolving animal phyla, nematodes and platyhelminths, emerge either at the base of all other Bilateria, or within protostomes, depending on the outgroup. We use this artefactual result as a case study for comparing the robustness of two alternative models: a standard, site homogeneous model, based on an empirical matrix of amino-acid replacement (WAG), and a site-heterogeneous mixture model (CAT). In parallel, we propose a posterior predictive test, allowing one to measure how well a model acknowledges sequence saturation. RESULTS: Adopting a Bayesian framework, we show that the LBA artefact observed under WAG disappears when the site-heterogeneous model CAT is used. Using cross-validation, we further demonstrate that CAT has a better statistical fit than WAG on this data set. Finally, using our statistical goodness-of-fit test, we show that CAT, but not WAG, correctly accounts for the overall level of saturation, and that this is due to a better estimation of site-specific amino acid preferences. CONCLUSION: The CAT model appears to be more robust than WAG against LBA artefacts, essentially because it correctly anticipates the high probability of convergences and reversions implied by the small effective size of the amino-acid alphabet at each site of the alignment. More generally, our results provide strong evidence that site-specificities in the substitution process need be accounted for in order to obtain more reliable phylogenetic trees. PMID- 17288578 TI - Methods for selecting fixed-effect models for heterogeneous codon evolution, with comments on their application to gene and genome data. AB - BACKGROUND: Models of codon evolution have proven useful for investigating the strength and direction of natural selection. In some cases, a priori biological knowledge has been used successfully to model heterogeneous evolutionary dynamics among codon sites. These are called fixed-effect models, and they require that all codon sites are assigned to one of several partitions which are permitted to have independent parameters for selection pressure, evolutionary rate, transition to transversion ratio or codon frequencies. For single gene analysis, partitions might be defined according to protein tertiary structure, and for multiple gene analysis partitions might be defined according to a gene's functional category. Given a set of related fixed-effect models, the task of selecting the model that best fits the data is not trivial. RESULTS: In this study, we implement a set of fixed-effect codon models which allow for different levels of heterogeneity among partitions in the substitution process. We describe strategies for selecting among these models by a backward elimination procedure, Akaike information criterion (AIC) or a corrected Akaike information criterion (AICc). We evaluate the performance of these model selection methods via a simulation study, and make several recommendations for real data analysis. Our simulation study indicates that the backward elimination procedure can provide a reliable method for model selection in this setting. We also demonstrate the utility of these models by application to a single-gene dataset partitioned according to tertiary structure (abalone sperm lysin), and a multi-gene dataset partitioned according to the functional category of the gene (flagellar-related proteins of Listeria). CONCLUSION: Fixed-effect models have advantages and disadvantages. Fixed-effect models are desirable when data partitions are known to exhibit significant heterogeneity or when a statistical test of such heterogeneity is desired. They have the disadvantage of requiring a priori knowledge for partitioning sites. We recommend: (i) selection of models by using backward elimination rather than AIC or AICc, (ii) use a stringent cut-off, e.g., p = 0.0001, and (iii) conduct sensitivity analysis of results. With thoughtful application, fixed-effect codon models should provide a useful tool for large scale multi-gene analyses. PMID- 17288579 TI - Rapid divergence of codon usage patterns within the rice genome. AB - BACKGROUND: Synonymous codon usage varies widely between genomes, and also between genes within genomes. Although there is now a large body of data on variations in codon usage, it is still not clear if the observed patterns reflect the effects of positive Darwinian selection acting at the level of translational efficiency or whether these patterns are due simply to the effects of mutational bias. In this study, we have included both intra-genomic and inter-genomic comparisons of codon usage. This allows us to distinguish more efficiently between the effects of nucleotide bias and translational selection. RESULTS: We show that there is an extreme degree of heterogeneity in codon usage patterns within the rice genome, and that this heterogeneity is highly correlated with differences in nucleotide content (particularly GC content) between the genes. In contrast to the situation observed within the rice genome, Arabidopsis genes show relatively little variation in both codon usage and nucleotide content. By exploiting a combination of intra-genomic and inter-genomic comparisons, we provide evidence that the differences in codon usage among the rice genes reflect a relatively rapid evolutionary increase in the GC content of some rice genes. We also noted that the degree of codon bias was negatively correlated with gene length. CONCLUSION: Our results show that mutational bias can cause a dramatic evolutionary divergence in codon usage patterns within a period of approximately two hundred million years. The heterogeneity of codon usage patterns within the rice genome can be explained by a balance between genome-wide mutational biases and negative selection against these biased mutations. The strength of the negative selection is proportional to the length of the coding sequences. Our results indicate that the large variations in synonymous codon usage are not related to selection acting on the translational efficiency of synonymous codons. PMID- 17288580 TI - Phylogenetic signal and functional categories in Proteobacteria genomes. AB - BACKGROUND: A comprehensive evolutionary analysis of bacterial genomes implies to identify the hallmark of vertical and non-vertical signals and to discriminate them from the presence of mere phylogenetic noise. In this report we have addressed the impact of factors like the universal distribution of the genes, their essentiality or their functional role in the cell on the inference of vertical signal through phylogenomic methods. RESULTS: We have established that supermatrices derived from data sets composed mainly by genes suspected to be essential for bacterial cellular life perform better on the recovery of vertical signal than those composed by widely distributed genes. In addition, we show that the "Transcription" category of genes seems to harbor a better vertical signal than other functional categories. Moreover, the "Poorly characterized" category performs better than other categories related with metabolism or cellular processes. CONCLUSION: From these results we conclude that different data sets allow addressing different questions in phylogenomic analyses. The vertical signal seems to be more present in essential genes although these also include a significant degree of incongruence. From a functional perspective, as expected, informational genes perform better than operational ones but we have also shown the surprising behavior of poorly annotated genes, which points to their importance in the genome evolution of bacteria. PMID- 17288582 TI - Detecting non-coding selective pressure in coding regions. AB - BACKGROUND: Comparative genomics approaches, where orthologous DNA regions are compared and inter-species conserved regions are identified, have proven extremely powerful for identifying non-coding regulatory regions located in intergenic or intronic regions. However, non-coding functional elements can also be located within coding region, as is common for exonic splicing enhancers, some transcription factor binding sites, and RNA secondary structure elements affecting mRNA stability, localization, or translation. Since these functional elements are located in regions that are themselves highly conserved because they are coding for a protein, they generally escaped detection by comparative genomics approaches. RESULTS: We introduce a comparative genomics approach for detecting non-coding functional elements located within coding regions. Codon evolution is modeled as a mixture of codon substitution models, where each component of the mixture describes the evolution of codons under a specific type of coding selective pressure. We show how to compute the posterior distribution of the entropy and parsimony scores under this null model of codon evolution. The method is applied to a set of growth hormone 1 orthologous mRNA sequences and a known exonic splicing elements is detected. The analysis of a set of CORTBP2 orthologous genes reveals a region of several hundred base pairs under strong non coding selective pressure whose function remains unknown. CONCLUSION: Non-coding functional elements, in particular those involved in post-transcriptional regulation, are likely to be much more prevalent than is currently known. With the numerous genome sequencing projects underway, comparative genomics approaches like that proposed here are likely to become increasingly powerful at detecting such elements. PMID- 17288581 TI - The role of laterally transferred genes in adaptive evolution. AB - BACKGROUND: Bacterial genomes develop new mechanisms to tide them over the imposing conditions they encounter during the course of their evolution. Acquisition of new genes by lateral gene transfer may be one of the dominant ways of adaptation in bacterial genome evolution. Lateral gene transfer provides the bacterial genome with a new set of genes that help it to explore and adapt to new ecological niches. METHODS: A maximum likelihood analysis was done on the five sequenced corynebacterial genomes to model the rates of gene insertions/deletions at various depths of the phylogeny. RESULTS: The study shows that most of the laterally acquired genes are transient and the inferred rates of gene movement are higher on the external branches of the phylogeny and decrease as the phylogenetic depth increases. The newly acquired genes are under relaxed selection and evolve faster than their older counterparts. Analysis of some of the functionally characterised LGTs in each species has indicated that they may have a possible adaptive role. CONCLUSION: The five Corynebacterial genomes sequenced to date have evolved by acquiring between 8-14% of their genomes by LGT and some of these genes may have a role in adaptation. PMID- 17288583 TI - Depression in cancer patients: a critical review. AB - Cancer patients experience several stressors and emotional upheavals. Fear of death, interruption of life plans, changes in body image and self-esteem, changes in social role and lifestyle are all important issues to be faced. Moreover, Depressive Disorders may impact the course of the disease and compliance. The cost and prevalence, the impairment caused, and the diagnostic and therapeutic uncertainty surrounding depressive symptoms among cancer patients make these conditions a priority for research. In this article we discuss recent data, focusing on detection of Depressive Disorders, biological correlates, treatments and unmet needs of depressed cancer patients. PMID- 17288584 TI - Combining an SSRI with an anticonvulsant in depressed patients with dysphoric mood: an open study. AB - BACKGROUND: Several patients with unipolar depression present with prominent dysphoric mood. We aimed at examining the effectiveness of the combination of an SSRI with an anticonvulsant in such patients. METHODS: Thirty-five newly admitted outpatients with substantial anger, irritability, aggressiveness or hostility who were diagnosed a DSM-IV unipolar depressive disorder were rated on the Hamilton Depression Rating Scale (HDRS), the Clinical Global Improvement (CGI) scale, and a scale for the rapid dimensional assessment (SVARAD), were prescribed an SSRI and an anticonvulsant (usually valproate), and were followed up for 12 weeks. Repeated measures analysis of variance was used to test for within-subject changes in scale scores over time. RESULTS: Thirty-two and 23 patients attended the follow-up visits 4 and 12 weeks later, respectively. Significant decreases (p < .001) were observed in HDRS total score, HDRS and SVARAD anxiety factors, HDRS and SVARAD core depression factors, and SVARAD anger/irritability factor. Adjusting for age or gender did not change the results. Most patients (82%) were rated as improved or much improved on the CGI. CONCLUSION: Although our study has several limitations, we observed a remarkable improvement in most unipolar depressed outpatients with dysphoric mood treated with an SSRI and an anticonvulsant. The effectiveness of anticonvulsants might be linked to their action on symptoms of aggression and behavioural activation. PMID- 17288585 TI - Protein, iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study. AB - A recent prospective study showed that higher consumption of red meat and total protein was associated with increased risk for inflammatory polyarthritis. We therefore prospectively examined the relationship between diet (in particular, protein, iron, and corresponding food sources) and incident rheumatoid arthritis (RA) among 82,063 women in the Nurses' Health Study. From 1980 to 2002, 546 incident cases of RA were confirmed by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria for RA. Diet was assessed at baseline in 1980 and five additional times during follow up. We conducted Cox proportional hazards analyses to calculate the rate ratio of RA associated with intakes of protein (total, animal, and vegetable) and iron (total, dietary, from supplements, and heme iron) and their primary food sources, adjusting for age, smoking, body mass index, and reproductive factors. The multivariate models revealed no association between RA and any measure of protein or iron intake. In comparisons of highest with lowest quintiles of intake, the rate ratio for total protein was 1.17 (95% confidence interval 0.89-1.54; P for trend = 0.11) and for total iron it was 1.04 (95% confidence interval 0.77-1.41; P for trend = 0.82). Red meat, poultry, and fish were also not associated with RA risk. We were unable to confirm that there is an association between protein or meat and risk for RA in this large female cohort. Iron was also not associated with RA in this cohort. PMID- 17288587 TI - World Journal of Emergency Surgery (WJES), World Society of Emergency Surgery (WSES) and the role of emergency surgery in the world. PMID- 17288586 TI - Prognosis of chronic low back pain: design of an inception cohort study. AB - BACKGROUND: Although clinical guidelines generally portray chronic low back pain as a condition with a poor prognosis this portrayal is based on studies of potentially unrepresentative survival cohorts. The aim of this study is to describe the prognosis of an inception cohort of people with chronic low back pain presenting for primary care. METHODS/DESIGN: The study will be an inception cohort study with one year follow-up. Participants are drawn from a cohort of consecutive patients presenting with acute low back pain (less than 2 weeks duration) to primary care clinics in Sydney, Australia. Those patients who continue to experience pain at three months, and are therefore classified as having chronic back pain, are invited to participate in the current study. The cohort will be followed up by telephone at baseline, 9 months and 12 months after being diagnosed with chronic low back pain. Recovery from low back pain will be measured by sampling three different outcomes: pain intensity, interference with function due to pain, and work status. Life tables will be generated to determine the one year prognosis of chronic low back pain. Prognostic factors will be assessed using Cox regression. DISCUSSION: This study will determine the prognosis of chronic non-specific low back pain in a representative cohort of patients sourced from primary care. The results of this study will improve understanding of chronic low back pain, allowing clinicians to provide more accurate prognostic information to their patients. PMID- 17288588 TI - Alterated integrin expression in lichen planopilaris. AB - BACKGROUND: Lichen planopilaris (LPP) is an inflammatory disease characterized by a lymphomononuclear infiltrate surrounding the isthmus and infundibulum of the hair follicle of the scalp, that evolves into atrophic/scarring alopecia. In the active phase of the disease hairs are easily plucked with anagen-like hair-roots. In this study we focused on the expression of integrins and basement membrane components of the hair follicle in active LPP lesions. METHODS: Scalp biopsies were taken in 10 patients with LPP and in 5 normal controls. Using monoclonal antibodies against alpha3beta1 and alpha6beta4 integrins we showed the expression of these integrins and of the basement membrane components of the hair follicle in active LPP lesions and in healthy scalp skin. RESULTS: In the LPP involved areas, alpha3beta1 was distributed in a pericellular pattern, the alpha6 subunit was present with a basolateral distribution while the beta4 subunit showed discontinuous expression at the basal pole and occasionally, basolateral staining of the hair follicle. CONCLUSION: An altered distribution of the integrins in active LPP lesions can explain the phenomenon of easy pulling-out of the hair with a "gelatinous" root-sheath. PMID- 17288589 TI - Conserved intron positions in ancient protein modules. AB - BACKGROUND: The timing of the origin of introns is of crucial importance for an understanding of early genome architecture. The Exon theory of genes proposed a role for introns in the formation of multi-exon proteins by exon shuffling and predicts the presence of conserved splice sites in ancient genes. In this study, large-scale analysis of potential conserved splice sites was performed using an intron-exon database (ExInt) derived from GenBank. RESULTS: A set of conserved intron positions was found by matching identical splice sites sequences from distantly-related eukaryotic kingdoms. Most amino acid sequences with conserved introns were homologous to consensus sequences of functional domains from conserved proteins including kinases, phosphatases, small GTPases, transporters and matrix proteins. These included ancient proteins that originated before the eukaryote-prokaryote split, for instance the catalytic domain of protein phosphatase 2A where a total of eleven conserved introns were found. Using an experimental setup in which the relation between a splice site and the ancientness of its surrounding sequence could be studied, it was found that the presence of an intron was positively correlated to the ancientness of its surrounding sequence. Intron phase conservation was linked to the conservation of the gene sequence and not to the splice site sequence itself. However, no apparent differences in phase distribution were found between introns in conserved versus non-conserved sequences. CONCLUSION: The data confirm an origin of introns deep in the eukaryotic branch and is in concordance with the presence of introns in the first functional protein modules in an 'Exon theory of genes' scenario. A model is proposed in which shuffling of primordial short exonic sequences led to the formation of the first functional protein modules, in line with hypotheses that see the formation of introns integral to the origins of genome evolution. PMID- 17288591 TI - Impact of the 16th International Conference on AIDS: can these conferences lead to policy change? AB - This Commentary reflects on the success of the XVI International Conference on AIDS, that was held in Toronto between August 13-18, 2006. Not only was the Conference judged to have been a scientific success, it will probably also be recognized over time as having had important political impact. It is vital that scientists and policy-makers continue to be able to interact at these meetings as part of global efforts to combat the HIV epidemic. PMID- 17288590 TI - Low concentrations of transforming growth factor-beta-1 induce tubulogenesis in cultured mammary epithelial cells. AB - BACKGROUND: Formation of branching tubes is a fundamental step in the development of glandular organs. To identify extracellular cues that orchestrate epithelial tubulogenesis, we employed an in vitro assay in which EpH4-J3B1A mammary epithelial cells form spheroidal cysts when grown in collagen gels under serum free conditions, but form branching tubules in the presence of fetal calf serum (FCS). RESULTS: Initial experiments showed that the tubulogenesis-inducing activity of FCS was markedly increased by heating (70 degrees C) or transient acidification to pH3. We therefore hypothesized that the tubulogenic agent was transforming growth factor-beta (TGF-beta), a cytokine that is present in serum in latent form and can be activated by heat or acid treatment. We found indeed that the tubulogenic activity of acidified FCS is abrogated by addition of either SB-431542, a selective inhibitor of the TGF-beta type I receptor, or a neutralizing antibody to TGF-beta-1. On the other hand, addition of low concentrations (20-100 pg/ml) of exogenous TGF-beta-1 recapitulated the effect of acidified FCS in inducing morphogenesis of hollow tubes. In contrast, higher concentrations of TGF-beta-1 induced the formation of thin cellular cords devoid of a detectable lumen. To gain insight into the mechanisms underlying TGF-beta-1 induced tube formation, we assessed the potential role of matrix metalloproteinases (MMPs). By western blot and gelatin zymography, we observed a dose-dependent increase in MMP-9 upon TGF-beta-1 treatment. Tube formation was suppressed by a synthetic broad-spectrum metalloproteinase inhibitor, by recombinant tissue inhibitor of metalloproteinases-2 (TIMP-2) and by a selective inhibitor of MMP-9, indicating that this morphogenetic process requires the activity of MMP-9. CONCLUSION: Altogether, our results provide evidence that, at low concentrations, TGF-beta-1 promotes MMP-dependent branching tubulogenesis by mammary epithelial cells in vitro, and suggest that it plays a similar role during mammary gland development in vivo. PMID- 17288593 TI - Persistent problems of access to appropriate, affordable TB services in rural China: experiences of different socio-economic groups. AB - BACKGROUND: Large-scale Tuberculosis (TB) control programmes in China have been hailed a success. Concerns remain, however, about whether the programme is reaching all sections of the population, particularly poorer groups within rural communities, and whether there are hidden costs. This study takes a household perspective to investigate receipt of appropriate care and affordability of services for different socio-economic groups with TB symptoms in rural China. METHODS: Secondary analysis of Chinese National Household Health Survey for 2003: 40,000 rural households containing 143,991 individuals, 2,308 identified as TB suspects. OUTCOMES: use of services and expenditure of TB suspects, by gender and socio-economic position, indicated by household income, education, material assets, and insurance status. RESULTS: 37% of TB suspects did not seek any professional care, with low-income groups less likely to seek care than more affluent counterparts. Of those seeking care, only 35% received any of the recommended diagnostic tests. Of the 182 patients with a confirmed TB diagnosis, 104 (57%) received treatment at the recommended level, less likely if lacking health insurance or material assets. The burden of payment for services amounted to 45% of annual household income for the low-income group, 16% for the high income group. CONCLUSION: Access to appropriate, affordable TB services is still problematic in some rural areas of China, and receipt of care and affordability declines with declining socio-economic position. These findings highlight the current shortcomings of the national TB control programme in China and the formidable challenge it faces if it is to reach all sections of the population, including the poor with the highest burden of disease. PMID- 17288594 TI - Papillary glioneuronal tumor: a new entity awaiting inclusion in WHO classification. AB - Papillary glioneuronal tumor (PGNT) is a recently described lesion of the brain, which is still not included as a separate entity in WHO classification. To date 32 cases of PGNT have been reported in the world literature. We report the 33rd case, a 41-year-old male who presented with pain in the nape of the neck. MRI showed a large, predominantly solid mass involving the cerebral parenchyma of the left temporal and parieto-occipital lobes with extension across the midline. Histologically, it was a mixture of glial and neuronal components. Architecturally, the tumor was notable for its pseudopapillary pattern with hyalinized vessels. PGNT is considered as a low grade neoplasm and surgical excision has been curative in most of the cases. More cases of PGNT need to be reported as they may add further knowledge about its biologic behavior and allow its recognition and classification. PMID- 17288592 TI - Control of human trophoblast function. AB - The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane ligands and receptors, as well as by hormone and local factor release. During blastocyst implantation, generation of distinct trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal exchanges and the latter binds the placental body to the uterine wall. Physiological placentation is characterized by the invasion of the uterine spiral arteries by extravillous trophoblast cells arising from anchoring villi. Due to this invasion, the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells. This transformation establishes a low-resistance, high-capacity perfusion system from the radial arteries to the intervillous space, in which the villous tree is embedded. The physiology of pregnancy depends upon the orderly progress of structural and functional changes of villous and extravillous trophoblast, whereas a derangement of such processes can lead to different types of complications of varying degrees of gravity, including possible pregnancy loss and maternal life-threatening diseases. In this review we describe the mechanisms which regulate trophoblast differentiation, proliferation, migration and invasiveness, and the alterations in these mechanisms which lead to pathological conditions. Furthermore, based on the growing evidence that proper inflammatory changes and oxidative balance are needed for successful gestation, we explain the mechanisms by which agents able to influence such processes may be useful in the prevention and treatment of pregnancy disorders. PMID- 17288595 TI - "NeuroStem Chip": a novel highly specialized tool to study neural differentiation pathways in human stem cells. AB - BACKGROUND: Human stem cells are viewed as a possible source of neurons for a cell-based therapy of neurodegenerative disorders, such as Parkinson's disease. Several protocols that generate different types of neurons from human stem cells (hSCs) have been developed. Nevertheless, the cellular mechanisms that underlie the development of neurons in vitro as they are subjected to the specific differentiation protocols are often poorly understood. RESULTS: We have designed a focused DNA (oligonucleotide-based) large-scale microarray platform (named "NeuroStem Chip") and used it to study gene expression patterns in hSCs as they differentiate into neurons. We have selected genes that are relevant to cells (i) being stem cells, (ii) becoming neurons, and (iii) being neurons. The NeuroStem Chip has over 1,300 pre-selected gene targets and multiple controls spotted in quadruplicates (approximately 46,000 spots total). In this study, we present the NeuroStem Chip in detail and describe the special advantages it offers to the fields of experimental neurology and stem cell biology. To illustrate the utility of NeuroStem Chip platform, we have characterized an undifferentiated population of pluripotent human embryonic stem cells (hESCs, cell line SA02). In addition, we have performed a comparative gene expression analysis of those cells versus a heterogeneous population of hESC-derived cells committed towards neuronal/dopaminergic differentiation pathway by co-culturing with PA6 stromal cells for 16 days and containing a few tyrosine hydroxylase-positive dopaminergic neurons. CONCLUSION: We characterized the gene expression profiles of undifferentiated and dopaminergic lineage-committed hESC-derived cells using a highly focused custom microarray platform (NeuroStem Chip) that can become an important research tool in human stem cell biology. We propose that the areas of application for NeuroStem microarray platform could be the following: (i) characterization of the expression of established, pre-selected gene targets in hSC lines, including newly derived ones, (ii) longitudinal quality control for maintained hSC populations, (iii) following gene expression changes during differentiation under defined cell culture conditions, and (iv) confirming the success of differentiation into specific neuronal subtypes. PMID- 17288596 TI - Introduction of the Thin Prep Imaging System (TIS): experience in a high volume academic practice. AB - OBJECTIVE: Since the introduction of the liquid-based ThinPrep testing in 1996, most cytology laboratories across the country have adopted the liquid-based cytology (LBC) for Pap test screening. Subsequent to wide-spread adoption of the ThinPrep Pap test, the ThinPrep Imaging System (TIS) Cytyc Corp, Marlborough, MA was introduced to improve the accuracy and efficiency of screening interpretation. We report our initial experience with the TIS at Magee Women's Hospital. We introduced the TIS in December 2004. METHODS: The imager assisted Pap test results over the first 12 months (December 2004 to December 2005) of implementation were reviewed and analyzed. Our implementation protocol included each cytotechnologist manually prescreening 200 negative slides to gain experience with the imager slides and serve as a quality check for the TIS. We re screened 3400 slides (200 slides each for 17 cytotechnologists) manually which were initially determined to be negative using the TIS. 104,457 Pap tests were imaged on the TIS. 95,899 manually screened Pap tests, 12 months prior to the introduction of the TIS (December 2003-November 2004) are taken as the historic control group for our study. RESULTS: The mean ASC-US rate employing the automated imager was 8.70% [9088/104,457]. The mean LSIL detection rate was 4.22% [4409/104,457]. The imager did not miss any detectable high-grade lesions during these months, with a HSIL (+) detection rate of 0.68% in comparison to 0.60% by manual screening confirmed by follow-up biopsies. The difference is statistically significant with a p value of 0.022. The definition of false negative rate for purposes of this study is calculated as the number of false negative cases identified out of number of negatives re-screened. The TIS false negative rate was estimated at 0.012% [4/3400]. CONCLUSION: The overall performance of the TIS in our lab appears to be highly satisfactory in terms of improving sensitivity in screening cervical precursor lesions. The increased accuracy of detection of HSIL indicates a positive impact of the TIS in our laboratory. PMID- 17288597 TI - Dual roles of the transmembrane protein p23/TMP21 in the modulation of amyloid precursor protein metabolism. AB - BACKGROUND: Alzheimer's disease (AD) is characterized by cerebral deposition of beta-amyloid (Abeta) peptides. Abeta is released from ectodomain cleaved amyloid precursor protein (APP) via intramembranous proteolysis by gamma-secretase, a complex consisting of presenilin and a few other proteins. p23/TMP21, a member of the p24 family type I transmembrane proteins, was recently identified as a presenilin complex component capable of modulating gamma-secretase cleavage. The p24 family proteins form oligomeric complexes and regulate vesicular trafficking in the early secretory pathway, but their role in APP trafficking has not been investigated. RESULTS: Here, we report that siRNA-mediated depletion of p23 in N2a neuroblastoma and HeLa cells produces concomitant knockdown of additional p24 family proteins and increases secretion of sAPP. Furthermore, intact cell and cell-free Abeta production increases following p23 knockdown, similar to data reported earlier using HEK293 cells. However, we find that p23 is not present in mature gamma-secretase complexes isolated using an active-site gamma-secretase inhibitor. Depletion of p23 and expression of a familial AD-linked PS1 mutant have additive effects on Abeta42 production. Knockdown of p23 expression confers biosynthetic stability to nascent APP, allowing its efficient maturation and surface accumulation. Moreover, immunoisolation analyses show decrease in co residence of APP and the APP adaptor Mint3. Thus, multiple lines of evidence indicate that p23 function influences APP trafficking and sAPP release independent of its reported role in gamma-secretase modulation. CONCLUSION: These data assign significance to p24 family proteins in regulating APP trafficking in the continuum of bidirectional transport between the ER and Golgi, and ascribe new relevance to the regulation of early trafficking in AD pathogenesis. PMID- 17288599 TI - Improved precision and accuracy for microarrays using updated probe set definitions. AB - BACKGROUND: Microarrays enable high throughput detection of transcript expression levels. Different investigators have recently introduced updated probe set definitions to more accurately map probes to our current knowledge of genes and transcripts. RESULTS: We demonstrate that updated probe set definitions provide both better precision and accuracy in probe set estimates compared to the original Affymetrix definitions. We show that the improved precision mainly depends on the increased number of probes that are integrated into each probe set, but we also demonstrate an improvement when the same number of probes is used. CONCLUSION: Updated probe set definitions does not only offer expression levels that are more accurately associated to genes and transcripts but also improvements in the estimated transcript expression levels. These results give support for the use of updated probe set definitions for analysis and meta analysis of microarray data. PMID- 17288600 TI - Contemporary organosilicon chemistry. AB - Editorial for the Thematic Series on Contemporary Organosilicon Chemistry. PMID- 17288598 TI - Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish. AB - BACKGROUND: Attempts to develop a mechanistic understanding of the effects of environmental estrogens on fish are increasingly conducted at the level of gene expression. Appropriate application of real-time PCR in such studies requires the use of a stably expressed 'housekeeping' gene as an internal control to normalize for differences in the amount of starting template between samples. RESULTS: We sought to identify appropriate genes for use as internal controls in experimental treatments with estrogen by analyzing the expression of eight functionally distinct 'housekeeping' genes (18S ribosomal RNA [18S rRNA], ribosomal protein l8 [rpl8], elongation factor 1 alpha [ef1a], glucose-6-phosphate dehydrogenase [g6pd], beta actin [bactin], glyceraldehyde-3-phosphate dehydrogenase [gapdh], hypoxanthine phosphoribosyltransferase 1 [hprt1], and tata box binding protein [tbp]) following exposure to the environmental estrogen, 17alpha-ethinylestradiol (EE2), in the fathead minnow (Pimephales promelas). Exposure to 10 ng/L EE2 for 21 days down-regulated the expression of ef1a, g6pd, bactin and gapdh in the liver, and bactin and gapdh in the gonad. Some of these effects were gender specific, with bactin in the liver and gapdh in the gonad down-regulated by EE2 in males only. Furthermore, when ef1a, g6pd, bactin or gapdh were used for normalization, the hepatic expression of two genes of interest, vitellogenin (vtg) and cytochrome P450 1A (cyp1a) following exposure to EE2 was overestimated. CONCLUSION: Based on the data presented, we recommend 18S rRNA, rpl8, hprt1 and/or tbp, but not ef1a, g6pd, bactin and/or gapdh, as likely appropriate internal controls in real-time PCR studies of estrogens effects in fish. Our studies show that pre-validation of control genes considering the scope and nature of the experiments to be performed, including both gender and tissue type, is critical for accurate assessments of the effects of environmental estrogens on gene expression in fish. PMID- 17288601 TI - Reaction of benzoxasilocines with aromatic aldehydes: Synthesis of homopterocarpans. AB - Condensation of 2H-benzo[g][1,2]oxasilocines with aromatic aldehydes in the presence of boron trifluoride affords mixtures of cis/trans 2-phenyl-3 vinylchromans with moderate yields. These can be transformed into homopterocarpans, a synthetic group of substances homologous to the natural isoflavonoid pterocarpans. PMID- 17288602 TI - Tether-directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes. AB - BACKGROUND: Using a silyl tether to unite an aldehyde electrophile and allylsilane nucleophile into a single molecule allows a subsequent Lewis-acid mediated allylation to proceed in an intramolecular sense and therefore receive all the benefits associated with such processes. However, with the ability to cleave the tether post allylation, a product that is the result of a net intermolecular reaction can be obtained. In the present study, four diastereoisomeric beta-silyloxy-alpha-methyl aldehydes, which contain an allylsilane tethered through the beta-carbinol centre, have been prepared, in order to probe how the relative configuration of the two stereogenic centres affects the efficiency and selectivity of the intramolecular allylation. RESULTS: Syn-aldehydes, syn-4a and syn-4b, both react poorly, affording all four possible diastereoisomeric oxasilacycle products. In contrast, the anti aldehydes anti-4a and anti-4b react analogously to substrates that lack substitution at the alpha site, affording only two of the four possible allylation products. CONCLUSION: The outcome of the reaction with anti-aldehydes is in accord with reaction proceeding through a chair-like transition state (T.S.). In these systems, the sense of 1,3-stereoinduction can be rationalised by the aldehyde electrophile adopting a pseudoaxial orientation, which will minimise dipole-dipole interactions in the T.S. The 1,4-stereoinduction in these substrates is modest and seems to be modulated by the R substituent in the starting material. In the case of the syn-substrates, cyclisation through a chair T.S. is unlikely as this would require the methyl substituent alpha to the reacting carbonyl group to adopt an unfavourable pseudoaxial position. It is therefore proposed that these substrates react through poorly-defined T.S.s and consequently exhibit essentially no stereoselectivity. PMID- 17288603 TI - Generation of pyridyl coordinated organosilicon cation pool by oxidative Si-Si bond dissociation. AB - An organosilicon cation stabilized by intramolecular pyridyl coordination was effectively generated and accumulated by oxidative Si-Si bond dissociation of the corresponding disilane using low temperature electrolysis, and was characterized by NMR and CSI-MS. PMID- 17288604 TI - Pd-catalysed [3 + 3] annelations in the stereoselective synthesis of indolizidines. AB - A [3 + 3] annelation of enantiomerically pure aziridine 7 provides the functionalised piperidine 8 that can be elaborated to the indolizidine skeleton in only 4 steps with good stereocontrol. PMID- 17288605 TI - Conformational rigidity of silicon-stereogenic silanes in asymmetric catalysis: A comparative study. AB - In recent years, cyclic silicon-stereogenic silanes were successfully employed as stereoinducers in transition metal-catalyzed asymmetric transformations as exemplified by (1) the hydrosilylation of alkenes constituting a chirality transfer from silicon to carbon and (2) the kinetic resolution of racemic mixtures of alcohols by dehydrogenative silicon-oxygen coupling. In this investigation, a cyclic and a structurally related acyclic silane with silicon centered chirality were compared using the above-mentioned model reactions. The stereochemical outcome of these pairs of reactions was correlated with and rationalized by the current mechanistic pictures. An acyclic silicon-stereogenic silane is also capable of inducing excellent chirality transfer (ct) in a palladium-catalyzed intermolecular carbon-silicon bond formation yet silicon incorporated into a cyclic framework is required in the copper-catalyzed silicon oxygen bond forming reaction. PMID- 17288607 TI - Revealing the burden of maternal mortality: a probabilistic model for determining pregnancy-related causes of death from verbal autopsies. AB - BACKGROUND: Substantial reductions in maternal mortality are called for in Millennium Development Goal 5 (MDG-5), thus assuming that maternal mortality is measurable. A key difficulty is attributing causes of death for the many women who die unaided in developing countries. Verbal autopsy (VA) can elicit circumstances of death, but data need to be interpreted reliably and consistently to serve as global indicators. Recent developments in probabilistic modelling of VA interpretation are adapted and assessed here for the specific circumstances of pregnancy-related death. METHODS: A preliminary version of the InterVA-M probabilistic VA interpretation model was developed and refined with adult female VA data from several sources, and then assessed against 258 additional VA interviews from Burkina Faso. Likely causes of death produced by the model were compared with causes previously determined by local physicians. Distinction was made between free-text and closed-question data in the VA interviews, to assess the added value of free-text material on the model's output. RESULTS: Following rationalisation between the model and physician interpretations, cause-specific mortality fractions were broadly similar. Case-by-case agreement between the model and any of the reviewing physicians reached approximately 60%, rising to approximately 80% when cases with a discrepancy were reviewed by an additional physician. Cardiovascular disease and malaria showed the largest differences between the methods, and the attribution of infections related to pregnancy also varied. The model estimated 30% of deaths to be pregnancy-related, of which half were due to direct causes. Data derived from free-text made no appreciable difference. CONCLUSION: InterVA-M represents a potentially valuable new tool for measuring maternal mortality in an efficient, consistent and standardised way. Further development, refinement and validation are planned. It could become a routine tool in research and service settings where levels and changes in pregnancy-related deaths need to be measured, for example in assessing progress towards MDG-5. PMID- 17288606 TI - The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis. AB - BACKGROUND: Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60-70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels > or =200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. METHODS: We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein > or = 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. RESULTS: For an elevation of alpha fetoprotein > or= 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate > or =7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. CONCLUSION: The progressive elevation of alpha fetoprotein > or =7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach alphaFP levels > or =200 ng/mL. Prospective studies are required to confirm this observation. PMID- 17288608 TI - MetaQTL: a package of new computational methods for the meta-analysis of QTL mapping experiments. AB - BACKGROUND: Integration of multiple results from Quantitative Trait Loci (QTL) studies is a key point to understand the genetic determinism of complex traits. Up to now many efforts have been made by public database developers to facilitate the storage, compilation and visualization of multiple QTL mapping experiment results. However, studying the congruency between these results still remains a complex task. Presently, the few computational and statistical frameworks to do so are mainly based on empirical methods (e.g. consensus genetic maps are generally built by iterative projection). RESULTS: In this article, we present a new computational and statistical package, called MetaQTL, for carrying out whole genome meta-analysis of QTL mapping experiments. Contrary to existing methods, MetaQTL offers a complete statistical process to establish a consensus model for both the marker and the QTL positions on the whole genome. First, MetaQTL implements a new statistical approach to merge multiple distinct genetic maps into a single consensus map which is optimal in terms of weighted least squares and can be used to investigate recombination rate heterogeneity between studies. Secondly, assuming that QTL can be projected on the consensus map, MetaQTL offers a new clustering approach based on a Gaussian mixture model to decide how many QTL underly the distribution of the observed QTL. CONCLUSION: We demonstrate using simulations that the usual model choice criteria from mixture model literature perform relatively well in this context. As expected, simulations also show that this new clustering algorithm leads to a reduction in the length of the confidence interval of QTL location provided that across studies there are enough observed QTL for each underlying true QTL location. The usefulness of our approach is illustrated on published QTL detection results of flowering time in maize. Finally, MetaQTL is freely available at http://bioinformatics.org/mqtl. PMID- 17288609 TI - Protein sequence database for pathogenic arenaviruses. AB - BACKGROUND: Arenaviruses are a family of rodent-borne viruses that cause several hemorrhagic fevers. These diseases can be devastating and are often lethal. Herein, to aid in the design and development of diagnostics, treatments and vaccines for arenavirus infections, we have developed a database containing protein sequences from the seven pathogenic arenaviruses (Junin, Guanarito, Sabia, Machupo, Whitewater Arroyo, Lassa and LCMV). RESULTS: The database currently contains a non-redundant set of 333 protein sequences which were manually annotated. All entries were linked to NCBI and cited PubMed references. The database has a convenient query interface including BLAST search. Sequence variability analyses were also performed and the results are hosted in the database. CONCLUSION: The database is available at http://epitope.liai.org:8080/projects/arena and can be used to aid in studies that require proteomic information from pathogenic arenaviruses. PMID- 17288611 TI - How effective is tetracaine 4% gel, before a venipuncture, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial. AB - BACKGROUND: Procedural pain relief is sub-optimal in neonates. Topical tetracaine provides pain relief in children. Evidence of its efficacy and safety in neonates is limited. The objective of this study was to assess the efficacy and safety of topical tetracaine on the pain response of neonates during a venipuncture. METHODS: Medically stable infants greater than or equal to 24 weeks gestation, requiring a venipuncture, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. Participants received oral sucrose if they met local eligibility criteria. The venipuncture was performed according to a standard protocol. A medium effect size in the pain score (corresponding to about 2 point difference in the PIPP score) was considered clinically significant, leading to a sample size of 142 infants, with 80% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. RESULTS: One hundred and forty two infants were included, 33 +/- 4 weeks gestation, 2100 +/- 900 grams and 6 +/- 3 days of age. There was almost no difference in PIPP scores at 1 minute between groups (mean difference -0.09; 95% confidence interval [CI]: -1.68 to 1.50; P = . 91). Similarly, there were no differences in PIPP scores during the 2nd, 3rd and 4th minute. Duration of cry did not differ between the groups (median difference, 0; 95% CI, -3 to 0; P = . 84). The majority of infants in both groups received sucrose 24%. Sucrose had a significant effect on the PIPP score, as assessed by an ANOVA model (p = 0.0026). Local skin erythema was observed transiently in 11 infants (7 in the tetracaine and 4 in the placebo group). No serious side effect was observed. CONCLUSION: Tetracaine did not significantly decrease procedural pain in infants undergoing a venipuncture, when used in combination with routine sucrose administration. PMID- 17288612 TI - Phylogenetic analyses of complete mitochondrial genome sequences suggest a basal divergence of the enigmatic rodent Anomalurus. AB - BACKGROUND: Phylogenetic relationships between Lagomorpha, Rodentia and Primates and their allies (Euarchontoglires) have long been debated. While it is now generally agreed that Rodentia constitutes a monophyletic sister-group of Lagomorpha and that this clade (Glires) is sister to Primates and Dermoptera, higher-level relationships within Rodentia remain contentious. RESULTS: We have sequenced and performed extensive evolutionary analyses on the mitochondrial genome of the scaly-tailed flying squirrel Anomalurus sp., an enigmatic rodent whose phylogenetic affinities have been obscure and extensively debated. Our phylogenetic analyses of the coding regions of available complete mitochondrial genome sequences from Euarchontoglires suggest that Anomalurus is a sister taxon to the Hystricognathi, and that this clade represents the most basal divergence among sampled Rodentia. Bayesian dating methods incorporating a relaxed molecular clock provide divergence-time estimates which are consistently in agreement with the fossil record and which indicate a rapid radiation within Glires around 60 million years ago. CONCLUSION: Taken together, the data presented provide a working hypothesis as to the phylogenetic placement of Anomalurus, underline the utility of mitochondrial sequences in the resolution of even relatively deep divergences and go some way to explaining the difficulty of conclusively resolving higher-level relationships within Glires with available data and methodologies. PMID- 17288613 TI - A matched-pair cluster design study protocol to evaluate implementation of the Canadian C-spine rule in hospital emergency departments: Phase III. AB - BACKGROUND: Physicians in Canadian emergency departments (EDs) annually treat 185,000 alert and stable trauma victims who are at risk for cervical spine (C spine) injury. However, only 0.9% of these patients have suffered a cervical spine fracture. Current use of radiography is not efficient. The Canadian C-Spine Rule is designed to allow physicians to be more selective and accurate in ordering C-spine radiography, and to rapidly clear the C-spine without the need for radiography in many patients. The goal of this phase III study is to evaluate the effectiveness of an active strategy to implement the Canadian C-Spine Rule into physician practice. Specific objectives are to: 1) determine clinical impact, 2) determine sustainability, 3) evaluate performance, and 4) conduct an economic evaluation. METHODS: We propose a matched-pair cluster design study that compares outcomes during three consecutive 12-months "before," "after," and "decay" periods at six pairs of "intervention" and "control" sites. These 12 hospital ED sites will be stratified as "teaching" or "community" hospitals, matched according to baseline C-spine radiography ordering rates, and then allocated within each pair to either intervention or control groups. During the "after" period at the intervention sites, simple and inexpensive strategies will be employed to actively implement the Canadian C-Spine Rule. The following outcomes will be assessed: 1) measures of clinical impact, 2) performance of the Canadian C-Spine Rule, and 3) economic measures. During the 12-month "decay" period, implementation strategies will continue, allowing us to evaluate the sustainability of the effect. We estimate a sample size of 4,800 patients in each period in order to have adequate power to evaluate the main outcomes. DISCUSSION: Phase I successfully derived the Canadian C-Spine Rule and phase II confirmed the accuracy and safety of the rule, hence, the potential for physicians to improve care. What remains unknown is the actual change in clinical behaviors that can be affected by implementation of the Canadian C-Spine Rule, and whether implementation can be achieved with simple and inexpensive measures. We believe that the Canadian C-Spine Rule has the potential to significantly reduce health care costs and improve the efficiency of patient flow in busy Canadian EDs. PMID- 17288614 TI - Are upright lateral cervical radiographs in the obtunded trauma patient useful? A retrospective study. AB - BACKGROUND: The best method for radiographic "clearance" of the cervical spine in obtunded patients prior to removal of cervical immobilization devices remains debated. Dynamic radiographs or MRI are thought to demonstrate unstable injuries, but can be expensive and cumbersome to obtain. An upright lateral cervical radiograph (ULCR) was performed in selected patients to investigate whether this study could provide this same information, to enable removal of cervical immobilization devices in the multiple trauma patient. METHODS: We retrospectively reviewed our experience with ULCR in 683 blunt trauma victims who presented over a 3-year period, with either a Glasgow Coma Score <13 or who were intubated at the time of presentation. RESULTS: ULCR was performed in 163 patients. Seven patients had studies interpreted to be abnormal, of which six were also abnormal, by either CT or MRI. The seventh patient's only abnormality was soft tissue swelling; MRI was otherwise normal. Six patients had ULCR interpreted as normal, but had abnormalities on either CT or MRI. None of the missed injuries required surgical stabilization, although one had a vertebral artery injury demonstrated on subsequent angiography. ULCR had an apparent sensitivity of 45.5% and specificity of 71.4%. CONCLUSION: ULCR are inferior to both CT and MRI in the detection of cervical injury in patients with normal plain radiographs. We therefore cannot recommend the use of ULCR in the obtunded trauma patient. PMID- 17288615 TI - Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis. AB - BACKGROUND: Cigarette smoke disrupts the protective barrier established by the airway epithelium through direct damage to the epithelial cells, leading to cell death. Since the morphology of the airway epithelium of smokers does not typically demonstrate necrosis, the most likely mechanism for epithelial cell death in response to cigarette smoke is apoptosis. We hypothesized that cigarette smoke directly up-regulates expression of apoptotic genes, which could play a role in airway epithelial apoptosis. METHODS: Microarray analysis of airway epithelium obtained by bronchoscopy on matched cohorts of 13 phenotypically normal smokers and 9 non-smokers was used to identify specific genes modulated by smoking that were associated with apoptosis. Among the up-regulated apoptotic genes was pirin (3.1-fold, p < 0.002), an iron-binding nuclear protein and transcription cofactor. In vitro studies using human bronchial cells exposed to cigarette smoke extract (CSE) and an adenovirus vector encoding the pirin cDNA (AdPirin) were performed to test the direct effect of cigarette smoke on pirin expression and the effect of pirin expression on apoptosis. RESULTS: Quantitative TaqMan RT-PCR confirmed a 2-fold increase in pirin expression in the airway epithelium of smokers compared to non-smokers (p < 0.02). CSE applied to primary human bronchial epithelial cell cultures demonstrated that pirin mRNA levels increase in a time-and concentration-dependent manner (p < 0.03, all conditions compared to controls). Overexpression of pirin, using the vector AdPirin, in human bronchial epithelial cells was associated with an increase in the number of apoptotic cells assessed by both TUNEL assay (5-fold, p < 0.01) and ELISA for cytoplasmic nucleosomes (19.3-fold, p < 0.01) compared to control adenovirus vector. CONCLUSION: These observations suggest that up-regulation of pirin may represent one mechanism by which cigarette smoke induces apoptosis in the airway epithelium, an observation that has implications for the pathogenesis of cigarette smoke-induced diseases. PMID- 17288616 TI - The impact of admission diagnosis on gastric emptying in critically ill patients. AB - INTRODUCTION: Disturbed gastric emptying (GE) occurs commonly in critically ill patients. Admission diagnoses are believed to influence the incidence of delayed GE and subsequent feed intolerance. Although patients with burns and head injury are considered to be at greater risk, the true incidence has not been determined by examination of patient groups of sufficient number. This study aimed to evaluate the impact of admission diagnosis on GE in critically ill patients. METHODS: A retrospective review of patient demographics, diagnosis, intensive care unit (ICU) admission details, GE, and enteral feeding was performed on an unselected cohort of 132 mechanically ventilated patients (94 males, 38 females; age 54 +/- 1.2 years; admission Acute Physiology and Chronic Health Evaluation II [APACHE II] score of 22 +/- 1) who had undergone GE assessment by 13C-octanoic acid breath test. Delayed GE was defined as GE coefficient (GEC) of less than 3.20 and/or gastric half-emptying time (t50) of more than 140 minutes. RESULTS: Overall, 60% of the patients had delayed GE and a mean GEC of 2.9 +/- 0.1 and t50 of 163 +/- 7 minutes. On univariate analysis, GE correlated significantly with older age, higher admission APACHE II scores, longer length of stay in ICU prior to GE measurement, higher respiratory rate, higher FiO2 (fraction of inspired oxygen), and higher serum creatinine. After these factors were controlled for, there was a modest relationship between admission diagnosis and GE (r = 0.48; P = 0.02). The highest occurrence of delayed GE was observed in patients with head injuries, burns, multi-system trauma, and sepsis. Delayed GE was least common in patients with myocardial injury and non-gastrointestinal post-operative respiratory failure. Patients with delayed GE received fewer feeds and stayed longer in ICU and hospital compared to those with normal GE. CONCLUSION: Admission diagnosis has a modest impact on GE in critically ill patients, even after controlling for factors such as age, illness severity, and medication, which are known to influence this function. PMID- 17288617 TI - Association of six YFP-myosin XI-tail fusions with mobile plant cell organelles. AB - BACKGROUND: Myosins are molecular motors that carry cargo on actin filaments in eukaryotic cells. Seventeen myosin genes have been identified in the nuclear genome of Arabidopsis. The myosin genes can be divided into two plant-specific subfamilies, class VIII with four members and class XI with 13 members. Class XI myosins are related to animal and fungal myosin class V that are responsible for movement of particular vesicles and organelles. Organelle localization of only one of the 13 Arabidopsis myosin XI (myosin XI-6; At MYA2), which is found on peroxisomes, has so far been reported. Little information is available concerning the remaining 12 class XI myosins. RESULTS: We investigated 6 of the 13 class XI Arabidopsis myosins. cDNAs corresponding to the tail region of 6 myosin genes were generated and incorporated into a vector to encode YFP-myosin tail fusion proteins lacking the motor domain. Chimeric genes incorporating tail regions of myosin XI-5 (At MYA1), myosin XI-6 (At MYA2), myosin XI-8 (At XI-B), myosin XI-15 (At XI-I), myosin XI-16 (At XI-J) and myosin XI-17 (At XI-K) were expressed transiently. All YFP-myosin-tail fusion proteins were targeted to small organelles ranging in size from 0.5 to 3.0 mum. Despite the absence of a motor domain, the fluorescently-labeled organelles were motile in most cells. Tail cropping experiments demonstrated that the coiled-coil region was required for specific localization and shorter tail regions were inadequate for targeting. Myosin XI-6 (At MYA2), previously reported to localize to peroxisomes by immunofluorescence, labeled both peroxisomes and vesicles when expressed as a YFP tail fusion. None of the 6 YFP-myosin tail fusions interacted with chloroplasts, and only one YFP-tail fusion appeared to sometimes co-localize with fluorescent proteins targeted to Golgi and mitochondria. CONCLUSION: 6 myosin XI tails, extending from the coiled-coil region to the C-terminus, label specific vesicles and/or organelles when transiently expressed as YFP fusions in plant cells. Although comparable constructs lacking the motor domain result in a dominant negative effect on organelle motility in animal systems, the plant organelles remained motile. YFP-myosin tail fusions provide specific labeling for vesicles of unknown composition, whose identity can be investigated in future studies. PMID- 17288618 TI - Associations of work-family conflicts with food habits and physical activity. AB - OBJECTIVE: This study examines the relationship between family-work conflicts with food habits and physical activity, and whether the relationship is dependent on family structure and work-related factors. DESIGN AND SETTING: Cross-sectional postal surveys were carried out in 2001 and 2002 among employees of the City of Helsinki, Finland, aged 40-60 years (n = 5346, response rate 66%; for women 70% and for men 60%). Dependent variables in logistic regression analyses were nationally recommended food habits and physical activity. Independent variables were work-family conflicts and family-work conflicts. Covariates included age, marital status, number of children, occupational class, working hours, time travelling to work, and physical and mental work load. RESULTS: Women reporting strong work-family conflicts were more likely to follow recommended food habits (odds ratio (OR) and 95% confidence intervals 1.49 (1.19-1.86)), but this relationship weakened when adjusting for work-related factors (OR 1.20 (0.93 1.55)). Women and men with strong family-work conflicts were less likely to report recommended food habits after adjusting for family structure and work related factors (women OR 0.75 (0.61-0.92), men OR 0.57 (0.34-0.96)). Women and men with strong work-family conflicts were less likely to follow the recommended amount of physical activity (women OR 0.76 (0.60-0.96), men OR 0.54 (0.34-0.87)). Additionally, women with strong family-work conflicts were less likely to follow the recommended amount of physical activity (OR 0.77 (0.63-0.94)). Adjusting for family and work-related factors did not affect these associations. CONCLUSIONS: Conflicts between paid work and family life are likely to constitute barriers for a physically active lifestyle and possibly also for healthy food habits. Improving the balance between work and family may provide a route for promoting health-related behaviours. PMID- 17288620 TI - An objective examination of consumer perception of nutrition information based on healthiness ratings and eye movements. AB - OBJECTIVE: Previous research on nutrition labelling has mainly used subjective measures. This study examines the effectiveness of two types of nutrition label using two objective measures: eye movements and healthiness ratings. DESIGN: Eye movements were recorded while participants made healthiness ratings for two types of nutrition label: standard and standard plus the Food Standards Agency's 'traffic light' concept. SETTING: University of Derby, UK. SUBJECTS: A total of 92 participants (mean age 31.5 years) were paid for their participation. None of the participants worked in the areas of food or nutrition. RESULTS: For the standard nutrition label, participant eye movements lacked focus and their healthiness ratings lacked accuracy. The traffic light system helped to guide the attention of the consumer to the important nutrients and improved the accuracy of the healthiness ratings of nutrition labels. CONCLUSIONS: Consumers have a lack of knowledge regarding how to interpret nutrition information for standard labels. The traffic light concept helps to ameliorate this problem by indicating important nutrients to which to pay attention. PMID- 17288619 TI - Characteristics of misreporters of dietary intake and physical activity. AB - OBJECTIVE: To characterise misreporters of energy intake (EI) and energy expenditure (EE). DESIGN: Cross-sectional study, using a validated position and motion instrument, ActiReg, as the reference method to study misreporters of EI and of EE. EI was measured using a dietary record and EE using a physical activity questionnaire (PAQ). Misreporters were defined as subjects outside the 95% confidence limits of agreement between EI or EE reported/EE measured. SETTING: Free-living Danish volunteers. SUBJECTS: One hundred and thirty-eight volunteers aged between 20 and 59 years. RESULTS: Body mass index, smoking, 'try to eat healthily' and worries about weight were related to degree of under reported EI. The percentage energy from added sugar was lowest (P < 0.001) and the percentage energy from protein (P < 0.001) highest in under-reporters compared with acceptable reporters. Subjects who reported being very physically active at work or in leisure time reported a higher EE than measured EE compared with less physically active subjects (P < 0.05). Likewise, subjects who regard themselves as fit or very fit reported a higher EE than subjects who regard themselves as moderately fit (P < 0.05). Possible over-reporters reported less time as very light activity (P = 0.007), more time as moderate activity (P = 0.01) and more time as vigorous activity (P = 0.02) than acceptable reporters. CONCLUSIONS: Under-reporting of EI should always be taken into consideration; however, only a few characteristics of under-reporters are consistent among studies. Misreporting of EI was more prevalent than misreporting of EE. The level of physical activity more than the time spent involved in various activities was misreported. PMID- 17288621 TI - Separate estimates of portion size were not essential for energy and nutrient estimation: results from the Southern Community Cohort food-frequency questionnaire pilot study. AB - OBJECTIVE: A food-frequency questionnaire (FFQ) was developed to assess habitual dietary intake in the Southern Community Cohort Study (SCCS), a prospective epidemiological study to analyse disparities in cancer and other chronic diseases between African-Americans and Whites. DESIGN: Frequency and portion size estimates were obtained for each of 104 foods. Daily intakes of 13 food groups, energy and 18 nutrients were computed. Each participant's rank and quintile classification of nutrient intakes was determined with and without the use of the subject's reported portion size. SUBJECTS: The sample was obtained from the SCCS pilot study conducted in Tennessee, Mississippi and Florida, and consisted of 209 adults, 54% African-American, with a mean (standard deviation) age of 57.1 (12.5) years. RESULTS: Correlations between the ranks from the two methods of estimation were high, ranging from 0.66 to 0.94 for food groups and 0.81 to 0.94 for nutrients. Pearson correlations were similarly high for food groups and nutrients. Concordance in exact quintile rank across the nutrient indices ranged from 52 to 70%, rising to 90-99% for concordance within adjacent quintiles. CONCLUSIONS: To reduce the respondents' burden and to increase data completeness, the assignment of a uniform portion size when scoring the SCCS FFQ was considered acceptable. PMID- 17288622 TI - Trends in fruit, vegetable and salad intakes in 9-10-year-old schoolchildren living in Liverpool, 2000-2005. AB - OBJECTIVE: To report on the fruit, vegetable and salad intakes of Liverpool schoolchildren aged 9-10 years over a 5-year period (2000-2005). DESIGN: Cross sectional observational study. SETTING: Between 75 and 100 Liverpool primary schools took part in each survey year. SUBJECTS: Subjects consisted of five separate cohorts of 9-10-year-old children from all areas of the city. MAIN OUTCOME MEASURES: Number and proportion of boys and girls who reported eating fruit, vegetables and salad on the previous day. RESULTS: There was an upward trend in the reported intake of fruit between 2002 and 2005. Girls were more likely than boys to report eating fruit (P < 0.001). The trend in salad intake was positive. Between 2000 and 2005 there were significant increases in the number of boys (chi2 = 17.57, P = 0.001) and girls (chi2 = 80.56, P = 0.001) eating salad. Girls were significantly more likely to eat salad than boys in all years (chi2 = 58.75, P = 0.001). Trends in vegetable intake were similar to those for salad, with both sexes reporting yearly increases over the 5-year period. The increase in the number of boys who reported eating vegetables between 2000 and 2005 was 23.5% (chi2 = 32.9, P = 0.000). In girls there was a 44.8% increase over the same period (chi2 = 110.3, P < 0.000). CONCLUSIONS: The data reveal positive trends in the fruit, vegetable and salad intakes of Liverpool schoolchildren between 2000 and 2005. Further research is needed to elucidate the specific factors that have enabled the changes to take place. PMID- 17288623 TI - Which food-related behaviours are associated with healthier intakes of fruits and vegetables among women? AB - OBJECTIVE: To examine associations between shopping, food preparation, meal and eating behaviours and fruit and vegetable intake among women. DESIGN: Cross sectional survey. SETTING: Community-based sample from metropolitan Melbourne, Australia. SUBJECTS: A sample of 1136 women aged 18-65 years, randomly selected from the electoral roll. RESULTS: Food-related behaviours reflecting organisation and forward-planning, as well as enjoyment of and high perceived value of meal shopping, preparation and consumption were associated with healthier intakes of fruits and vegetables. For example, women who more frequently planned meals before they went shopping, wrote a shopping list, enjoyed food shopping, planned in the morning what they will eat for dinner that night, planned what they will eat for lunch, reported they enjoy cooking, liked trying new recipes and who reported they sometimes prepare dishes ahead of time were more likely to consume two or more servings of vegetables daily. Conversely, women who frequently found cooking a chore, spent less than 15 minutes preparing dinner, decided on the night what they will eat for dinner, ate in a fast-food restaurant, ate takeaway meals from a fast-food restaurant, ate dinner and snacks while watching television and who frequently ate on the run were less likely to eat two or more servings of vegetables daily. CONCLUSIONS: Practical strategies based on these behavioural characteristics could be trialled in interventions aimed at promoting fruit and vegetable consumption among women. PMID- 17288624 TI - The influence of fruit and vegetable intake on the nutritional status and plasma homocysteine levels of institutionalised elderly people. AB - OBJECTIVE: To determine the difference in the nutritional status of elderly people depending on their consumption of fruits and vegetables, and to study the possible association between the consumption of these foods and different cardiovascular risk factors, especially total plasma homocysteine (t-Hcys) levels. DESIGN, SETTING AND SUBJECTS: A cross-sectional study in 152 institutionalised older people from Madrid aged > or = 65 years. Food and nutrient intakes were recorded over 7 days using the 'precise individual weighing' method. The weight, height, and waist and hip circumferences of all subjects were recorded, as were their alpha-erythrocyte glutathione reductase, serum B6, B12 and folate levels, erythrocyte folate levels, t-Hcys levels, serum lipids and blood pressure. The experimental population was then divided into tertiles depending on the serving intake of fruit and vegetables (T1, < 2.29 servings day(-1); T2, 2.29-2.79 servings day(-1); and T3, >2.79 servings day( 1)). RESULTS: Compared with T1 subjects, T3 subjects showed consumptions of cereals, pulses, meat, fish and eggs closer to those recommended (P < 0.05). In addition, the contribution of their diet towards covering the recommended daily intake of vitamin B1, niacin, vitamin B6, folic acid, vitamin C, B12, vitamin A, and P, Mg, Zn and Fe was higher. The intake of fibre increased with consumption of fruit and vegetables (r = 0.6839, P < 0.001). T3 subjects also had better serum and erythrocyte folate levels than T1 and T2 subjects (P < 0.05). A positive correlation was found between the consumption of fruit and vegetables and serum folate (r = 0.2665, P < 0.01) and with erythrocyte folate levels (r = 0.2034, P < 0.05), and a negative correlation with t-Hcys (r = -0.2493, P < 0.01). CONCLUSIONS: Greater consumption of fruit and vegetables is associated with better food habits, increased vitamin and mineral intakes and lower t-Hcys levels. Considering that the fruit and vegetable intake in Spanish elderly people is very low, it is recommended that the consumption of fruits and vegetables by elderly people be increased. PMID- 17288625 TI - School-based internet-tailored fruit and vegetable education combined with brief counselling increases children's awareness of intake levels. AB - OBJECTIVE: Children's fruit/vegetable intake is still below recommended levels. This study applied Internet-tailored advice for schoolchildren and Internet supported brief dietary counselling (with child and parent) within preventive health care to promote fruit/vegetable intake. SETTING/SUBJECTS: The study involved 30 seventh-grade classes (16 in the intervention group and 14 in the control group) with a total of 675 children aged 9-12 years, of whom 495 were allowed to participate. DESIGN: A cluster-randomised baseline-post-test experimental design was applied. During school hours, all children completed Internet-administered questionnaires on fruit/vegetable intake and related determinants. Children in the intervention group received immediate online individually tailored nutrition feedback. For each child in the intervention group, a nurse received information concerning the assessment of fruit/vegetable intake via the Internet to support a 5 min counselling protocol to promote fruit/vegetable intake. Children completed a similar post-test questionnaire 3 months after the first assessment. Intention-to-treat analyses were conducted using multilevel regression analyses. RESULTS: A total of 486 children (98% of 495) participated (263 in the intervention group, 223 in the control group); 240 child-parent couples in the intervention group attended the counselling. Awareness of inadequate fruit intake (odds ratio (OR) = 3.0; 95% confidence interval (CI) = 1.8-5.3) and knowledge of recommended vegetable intake levels (OR = 2.7; 95% CI = 1.8-4.1) were significantly more likely at post-test in the intervention group than in the control group. No significant effects were found on intake or other determinants. CONCLUSIONS: A compact, integrated two-component intervention can induce positive changes in knowledge and awareness of intake levels of fruit/vegetables among schoolchildren. To induce changes in intake levels, more comprehensive interventions may be needed. PMID- 17288626 TI - Parent outcome expectancies for purchasing fruit and vegetables: a validation. AB - OBJECTIVE: To validate four scales -- outcome expectancies for purchasing fruit and for purchasing vegetables, and comparative outcome expectancies for purchasing fresh fruit and for purchasing fresh vegetables versus other forms of fruit and vegetables (F&V). DESIGN: Survey instruments were administered twice, separated by 6 weeks. SETTING: Recruited in front of supermarkets and grocery stores; interviews conducted by telephone. SUBJECTS: One hundred and sixty-one food shoppers with children (18 years or younger). RESULTS: Single dimension scales were specified for fruit and for vegetable purchasing outcome expectancies, and for comparative (fresh vs. other) fruit and vegetable purchasing outcome expectancies. Item Response Theory parameter estimates revealed easily interpreted patterns in the sequence of items by difficulty of response. Fruit and vegetable purchasing and fresh fruit comparative purchasing outcome expectancy scales were significantly correlated with home F&V availability, after controlling for social desirability of response. Comparative fresh vegetable outcome expectancy scale was significantly bivariately correlated with home vegetable availability, but not after controlling for social desirability. CONCLUSION: These scales are available to help better understand family F&V purchasing decisions. PMID- 17288627 TI - Comparison of buffet and a la carte serving at worksite canteens on nutrient intake and fruit and vegetable consumption. AB - OBJECTIVE: To evaluate the nutritional composition of worksite canteen lunches and to examine the impact of two meal serving systems on employee intake, i.e. buffet style with a fixed price for a varied number of dishes and a la carte style with a separate price for each item on the menu. DESIGN: Laboratory technicians observed employees' food selection and collected identical dishes. Food items were weighed separately to calculate the content of fruit and vegetables. The content of protein, fat and ash of each dish was chemically analysed and the carbohydrate and energy content calculated. SETTING: Fifteen randomly chosen worksite canteens in Denmark: eight canteens serving buffet style and seven canteens with an a la carte line. SUBJECTS: one hundred and eighty randomly chosen employees having lunch at the worksite canteens. RESULTS: The average percentage energy from fat was 37 +/- 12 among men and 33 +/- 12 among women. No association was found between the meal serving system and energy intake or macronutrient composition. Eating at canteens serving buffet style, on the other hand, was associated with an increased intake of fruit and vegetables, on average 76 g, and a lower energy density of the food for both genders. CONCLUSION: The results highlight the possibilities of promoting healthy food choices in the catering sector and the need to identify models of healthy catering practice. Serving buffet style appears to be a promising strategy in order to increase fruit and vegetable consumption in food served away from home. PMID- 17288629 TI - Lipid, protein and carbohydrate intake in relation to body mass index: an Italian study. AB - OBJECTIVE: To analyse the association between macronutrient intake and body mass index (BMI). DESIGN: A series of hospital-based case-control studies. SETTINGS: Selected teaching and general hospitals in several Italian regions. SUBJECTS: A total of 6619 subjects from the comparison groups of the case-control studies were included in the analysis. METHODS: We obtained data from a validated 78-item food-frequency questionnaire submitted between 1991 and 2002. For various macronutrients, the partial regression coefficient (variation of BMI (kg m(-2)) per 100 kcal increment of energy intake) was derived from multiple linear regression models, after allowance for age, study centre, education, smoking habits, number of eating episodes and mutual adjustment for macronutrients. RESULTS: BMI was directly associated with protein intake among women only (beta = 0.68) and with unsaturated fats in both genders (for monounsaturated fats beta = 0.27 for men and 0.26 for women; for polyunsaturated fats beta = 0.27 for men and 0.54 for women), and inversely related to carbohydrates (beta = -0.05 for men and -0.21 for women) and number of eating episodes in both genders (beta = -0.42 for men and -0.61 for women) and to saturated fats among women only (beta = -0.57). CONCLUSIONS: These results confirm and provide convincing evidence that, after allowance for selected covariates including total energy intake, a protein-rich diet is not inversely related to BMI, and a carbohydrate-rich diet is not directly related to BMI. PMID- 17288628 TI - Perceptions of weight and associated factors of adolescents in Jiangsu Province, China. AB - OBJECTIVE: To describe perceptions of weight of adolescents and associated factors. DESIGN: Cross-sectional survey in 2002. SETTING: Eight public middle schools in two distinct socio-economic areas of Jiangsu Province, China. SUBJECTS: Eight hundred and twenty-four adolescents (aged 12-14 years) and 628 of their parents. METHODS: Self-administered questionnaires for students and their parents were used to collect the data. Height and weight of the students were measured. RESULTS: One-third of the girls perceived themselves as overweight, while only 8.9% were actually overweight or obese according to the World Health Organization definition. On the other hand, 15.0% of the girls considered themselves underweight, while 5.6% were underweight according to the definition. Among the boys, one-fifth of those defined as overweight perceived their weight as normal. Furthermore, 23.9% perceived themselves as underweight when in fact only 4.9% were classified as underweight according to the definition. About one quarter of the students dieted in the past year. Adolescents who perceived themselves to be overweight dieted and skipped breakfast more often. They also had lower intake frequencies of animal foods, Western foods and milk/yoghurt. No disparity was observed in the intake frequency of fruits and vegetables between the groups of different weight perception. Parents' weight norms seemed to favour overweight in both genders, but especially among boys. CONCLUSIONS: Both overweight and underweight concerns were common among girls, while a higher body weight was favoured by normal-weight boys and their parents. Distorted weight perceptions in adolescents, as well as dieting, are problems that need appropriate intervention. PMID- 17288630 TI - Dietary intake among under-, normal- and overweight 9- and 15-year-old Estonian and Swedish schoolchildren. AB - OBJECTIVES: To determine the differences in macronutrient and food group contribution to total food and energy intakes between Estonian and Swedish under , normal- and overweight schoolchildren, and to estimate the association between diet and body mass index (BMI). DESIGN: Cross-sectional comparison between Estonian and Swedish children and adolescents of different BMI groups. SETTING: Twenty-five schools from one region in Estonia and 42 in two regions of central Sweden. SUBJECTS: In total 2308 participants (1176 from Estonia and 1132 from Sweden), including 1141 children with a mean age of 9.6 +/- 0.5 years and 1167 adolescents with a mean age of 15.5 +/- 0.6 years. RESULTS: Overweight was more prevalent among younger girls in Sweden (17.0 vs. 8.9%) and underweight among girls of both age groups in Estonia (7.9 vs. 3.5% in younger and 10.5 vs. 5.1% in older age group of girls). Compared with that of normal- and underweight peers, the diet of overweight Estonian children contained more energy as fat (36.8 vs. 31.7%) but less as carbohydrates, and they consumed more milk and meat products. Absolute BMI of Estonian participants was associated positively with energy consumption from eggs and negatively with energy consumption from sweets and sugar. Swedish overweight adolescents tended to consume more energy from protein and milk products. Risk of being overweight was positively associated with total energy intake and energy from fish or meat products. In both countries the association of overweight and biological factors (pubertal maturation, parental BMI) was stronger than with diet. CONCLUSION: The finding that differences in dietary intake between under-, normal- and overweight schoolchildren are country specific suggests that local dietary habits should be considered in intervention projects addressing overweight. PMID- 17288631 TI - Identification of taeniid eggs in the faeces from carnivores based on multiplex PCR using targets in mitochondrial DNA. AB - A multiplex polymerase chain reaction (PCR) was evaluated for the identification of morphologically indistinguishable eggs of the taeniid tapeworms from carnivores using primers targeting mitochondrial genes. The primers for Echinococcus multilocularis (amplicon size 395 bp) were species-specific as assessed by in silico analysis and in the PCR using well-defined control samples. The design of primers that specifically amplify DNA from E. granulosus or Taenia spp. was not possible. The primers designed for E. granulosus also amplified DNA (117 bp) from E. vogeli, and those designed for Taenia spp. amplified products (267 bp) from species of Mesocestoides, Dipylidium and Diphyllobothrium. Nevertheless, as our diagnostic approach includes the concentration of taeniid eggs by sequential sieving and flotation, followed by their morphological detection, this non-specificity has limited practical importance. Sequence analysis of the corresponding amplicon can identify most of the described E. granulosus genotypes. Taenia spp. can be identified by direct sequencing of the 267 bp amplicon, or, for most species, by restriction fragment length polymorphism (RFLP) analysis. The multiplex PCR was readily able to detect 1 egg (estimated to contain 7000 targets, as determined by quantitative PCR). Having been validated using a panel of well-defined samples from carnivores with known infection status, this approach proved to be useful for the identification of taeniid eggs from both individual animals and for epidemiological studies. PMID- 17288632 TI - Morphometric study of eosinophils, mast cells, macrophages and fibrosis in the colon of chronic chagasic patients with and without megacolon. AB - The mechanisms involved in the pathogenesis of chagasic megacolon are not completely characterized. Although autoimmunity may play a role in the pathogenesis of Chagas' disease, recent studies suggest a positive association of tissue parasitism, inflammation, and severity of lesions. The aim of this study was to evaluate the role of inflammatory cells and the occurrence of fibrosis in the colon of chagasic patients with and without megacolon. Samples from 26 patients were randomly selected and paraffin-embedded tissue blocks were sectioned and evaluated by histology and immunohistochemistry to analyse the occurrence and relation among eosinophils, mast cells, macrophages and fibrosis. Section analyses showed that the presence of eosinophils and mast cells in the analysed inflammatory cells has a direct correlation with fibrosis density in the chagasic megacolon. These data suggest that the megacolon's pathogenesis is based on a continuous process of cell damage. Our data propose that eosinophils, mast cells and macrophages may have a direct connection with the occurrence of fibrosis in the colon of chagasic patients. We believe that potential therapeutic agents against these cells could avoid the fibrosis process and contribute to prevent the development of chagasic megacolon. PMID- 17288633 TI - Haemoparasites of common shrews (Sorex araneus) in Northwest England. AB - The presence of haemoparasites belonging to the taxa Anaplasma, Bartonella and Trypanosoma was determined among 76 common shrews (Sorex araneus) from Northwest England. Anaplasma phagocytophilum DNA was recovered from the blood of 1 shrew (1.3%), with the amplified 16S rRNA sequence identical to one previously reported from a bank vole (Clethrionomys glareolus). Trypanosoma spp. DNA was detected in 9 shrews (11.8%), the amplified 18S rDNA fragments being indistinguishable from one another, and distinct from previously published data. This represents the first report of trypanosome infection in S. araneus and suggests they are susceptible to an uncharacterized Trypanosoma species. Blood from 11 shrews (14.5%) yielded Bartonella spp., with characterization of isolates using comparative sequence analysis of partial gltA and 16S-23S rRNA intergenic spacer regions revealing 2 different genotypes. Phylogenetic inference from alignment of partial gltA sequences found that both UK S. araneus types formed a well supported cluster with Bartonella sp. isolated from S. araneus in Sweden. No significant effect of host age, sex, or year of collection was found on prevalence of Bartonella or trypanosome infections. The results of this survey demonstrate that common shrews in the UK are susceptible to haemoparasitic infections, at prevalences similar to those reported from sympatric rodents. PMID- 17288634 TI - Endoparasitism in colonial hosts: patterns and processes. AB - This study begins to redress our lack of knowledge of the interactions between colonial hosts and their parasites by focusing on a novel host-parasite system. Investigations of freshwater bryozoan populations revealed that infection by myxozoan parasites is widespread. Covert infections were detected in all 5 populations studied and were often at high prevalence while overt infections were observed in only 1. Infections were persistent in populations subject to temporal sampling. Negative effects of infection were identified but virulence was low. Infection did not induce mortality in the environmental conditions studied. However, the production of statoblasts (dormant propagules) was greatly reduced in bryozoans with overt infections in comparison to uninfected bryozoans. Overtly infected bryozoans also grew more slowly and had low fission rates relative to colonies lacking overt infection. Bryozoans with covert infections were smaller than uninfected bryozoans. High levels of vertical transmission were achieved through colony fission and the infection of statoblasts. Increased fission rates may be a strategy for hosts to escape from parasites but the parasite can also exploit the fragmentation of colonial hosts to gain vertical transmission and dispersal. Our study provides evidence that opportunities and constraints for host-parasite co-evolution can be highly dependent on organismal body plans and that low virulence may be associated with exploitation of colonial hosts by endoparasites. PMID- 17288635 TI - Re-feeding rapidly restores protection against Heligmosomoides bakeri (Nematoda) in protein-deficient mice. AB - This study determined whether the timing of re-feeding of protein-deficient mice restored functional protection against the gastrointestinal nematode, Heligmosomoides bakeri. Balb/c mice were fed a 3% protein-deficient (PD) diet and then transferred to 24% protein-sufficient (PS) diet either on the day of primary infection, 10 days after the primary infection, on the day of challenge infection, or 7 days after the challenge infection. Control mice were fed either the PD or PS diet. Onset of challenge, but not primary, infection caused short term body weight loss, anorexia and reduced feed efficiency. Weight gain was delayed in mice when re-feeding commenced on the day of challenge infection; alkaline phosphatase (ALP) was also elevated in these mice on day 28 post challenge. In contrast, other re-feeding groups attained similar body weights to PS mice within 4 days and had similar ALP at day 28. Serum leptin was higher in PD than PS mice and positively associated with food intake. As expected, worm survival was prolonged in mice fed the PD diet. However, egg production and worm burdens were similar in all re-feeding groups to the PS mice, indicating that protein re-feeding during either the primary or challenge infection rapidly restored normal parasite clearance. PMID- 17288636 TI - Suicide ideation, plans and attempts in Ukraine: findings from the Ukraine World Mental Health Survey. AB - BACKGROUND: Because the suicide rates in Eastern Europe have increased, the epidemiology of suicide behaviors in this part of the world is in urgent need of study. Using data from the Ukraine site of the World Mental Health (WMH) Survey Initiative, we present the first population-based findings from a former Soviet country on the descriptive epidemiology of suicide ideation, plans and attempts, and their links to current functioning and service utilization. METHOD: In 2002, a nationally representative sample of 4725 adults in Ukraine was interviewed with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Risk factors included demographic characteristics, trauma, smoking, and parental and personal psychiatric disorders. Current functional impairments and recent service utilization were assessed. RESULTS: The lifetime prevalence of suicide ideation was 8.2%. The average age of onset was 31. The key risk factors were female sex, younger age, trauma, parental depression, and prior alcohol, depressive and intermittent explosive disorders, especially the presence of co morbidity. Ideators had poorer functioning and greater use of health services. One-third of ideators had a plan, and one-fifth made an attempt. Among ideators, young age, smoking and prior psychiatric disorders were risk factors for these behaviors. CONCLUSIONS: Together with the increasing suicide rate, these results suggest that suicide intervention programs in Ukraine should focus on the generation of young adults under 30. The associations with co-morbidity, impairments in current functioning and greater service use indicate that a physician education program on suicidality should be comprehensive in scope and a public health priority in Ukraine. PMID- 17288637 TI - Time since falling and fear of falling among community-dwelling elderly. AB - BACKGROUND: A fall experienced by an elderly person is of special note because it appears to hold a reciprocal causal association with the fear of falling. This study attempts to determine the temporal relationship between the fear of falling and falling among community-dwelling elderly. METHODS: Data on falls experienced during the previous three years were obtained from 732 community-dwelling elderly people. Participants were also asked to provide detailed information about their most recent fall, including the date, time of day, place, circumstances, consequences of the fall, fear of falling, and activity limitations due to fear of falling. RESULTS: Those who had fallen within the past six months had over four times greater odds of a fear of falling and approximately five times greater odds of activity restriction, compared with those who had not fallen. The association decreased linearly over time, and became nonsignificant for those who had not fallen during the past 25-36 months. CONCLUSIONS: The experience of a fall is strongly associated with an increased fear of falling, and the association appears to persist for at least two years. An elderly person who has experienced a fall requires continuous attention to prevent the development of fear as another problem, together with early intervention to counter the fear of falling. PMID- 17288638 TI - The temporal dynamics of relationships between cannabis, psychosis and depression among young adults with psychotic disorders: findings from a 10-month prospective study. AB - BACKGROUND: The aim was to examine the temporal relationships over 10 months between cannabis use and symptoms of psychosis and depression in people with schizophrenia and related disorders. The design was a prospective study of 101 patients with schizophrenia and related disorders who were assessed monthly over 10 months on medication compliance, cannabis and other drug use, symptoms of depression and symptoms of psychosis. METHOD: Linear regression methods to assess relationships between cannabis use and symptoms of psychosis and depression while adjusting for serial dependence, medication compliance and other demographic and clinical variables. RESULTS: Cannabis use predicted a small but statistically significant increase in symptoms of psychosis, but not depression, after controlling for other differences between cannabis users and non-users. Symptoms of depression and psychosis did not predict cannabis use. CONCLUSION: Continued cannabis use by persons with schizophrenia predicts a small increase in psychotic symptom severity but not vice versa. PMID- 17288639 TI - An outbreak of E. coli O157 associated with a swimming pool: an unusual vehicle of transmission. AB - Escherichia coli O157 causes a range of illnesses from mild diarrhoea to haemolytic uraemic syndrome (HUS) which carries a mortality rate of 3.7%. Infection is more common in the under-5s. Between 1995 and 2000, 106 outbreaks of E. coli O157 were reported in England and Wales. Recreational water is well documented as a transmission route for infectious diseases worldwide. In the United Kingdom there have been very few reported outbreaks associated with swimming pools due to the relative susceptibility of E. coli O157 to adequate levels of free chlorine. This report describes the investigation of an outbreak associated with a local leisure centre pool and makes recommendations about the safe management of such facilities. PMID- 17288640 TI - A community outbreak of Campylobacter jejuni infection from a chlorinated public water supply. AB - An outbreak of Campylobacter jejuni infection occurred in a South Wales Valleys housing estate. Illness in estate residents was associated with tap water consumption [population attributable risk (PAR) 50%, relative risk (RR) 2.53, 95% confidence interval (CI) 1.9-3.37] and residence in the upper estate (PAR 49%, RR 2.44, 95% CI 1.83-3.24). Amongst upper estate residents, rates of diarrhoeal illness increased with rates of water consumption (OR 18, 95% CI 3.5-92.4 for heaviest consumers, chi2 trend P<0.0001). The upper estate received mains water via a covered holding reservoir. A crack in the wall of the holding reservoir was identified. Contamination with surface water from nearby pasture land was the likely cause of this outbreak. Service reservoirs are common in rural communities and need regular maintenance and inspection. The role of water in sporadic cases of campylobacter enteritis may be underestimated. PMID- 17288641 TI - What happens to people diagnosed with tuberculosis? A population-based cohort. AB - We examined different patient outcomes following diagnosis of tuberculosis (TB). Incident cases were reported to the enhanced surveillance system in the East of England, between 2000 and 2003. For the 575 cases reported in 2001 and 2002, outcomes were assessed 1 year after initiating treatment. The crude clinical incidence rate of TB was 6.0 cases/100,000 person-years (pyr) [95% confidence interval (CI) 5.7-6.4], highest in the 25-29 years age group (14.9, 95% CI 12.9 17.1 cases/100,000 pyr) and among Black Africans (328.6, 95% CI 286.9-374.6 cases/100,000 pyr). Patients born abroad were 2.35 (95% CI 1.03-5.32) times more likely to be lost to follow-up than those born in the United Kingdom. Age at diagnosis (OR 1.05, 95% CI 1.04-1.07) and pulmonary disease (OR 2.73, 95% CI 1.21 6.15) were independently associated with mortality. Elderly patients and those with pulmonary TB appear to have worse outcomes despite treatment. Foreign-born patients may need closer follow-up to ensure favourable outcomes. PMID- 17288642 TI - Distribution of emm genotypes among group A streptococcus isolates from patients with severe invasive streptococcal infections in Japan, 2001-2005. AB - We surveyed emm genotypes of group A streptococcus (GAS) isolates from patients with severe invasive streptococcal infections during 2001-2005 and compared their prevalence with that of the preceding 5 years. Genotype emm1 remained dominant throughout 2001 to 2005, but the frequency rate of this type decreased compared with the earlier period. Various other emm types have appeared in recent years indicating alterations in the prevalent strains causing severe invasive streptococcal infections. The cover of the new 26-valent GAS vaccine fell from 93.5% for genotypes of isolates from 1996-2000 to 81.8% in 2001-2005. PMID- 17288643 TI - The impact of contact structure on infectious disease control: influenza and antiviral agents. AB - Planning adequate public health responses against emerging infectious diseases requires predictive tools to evaluate the impact of candidate intervention strategies. With current interest in pandemic influenza very high, modelling approaches have suggested antiviral treatment combined with targeted prophylaxis as an effective first-line intervention against an emerging influenza pandemic. To investigate how the effectiveness of such interventions depends on contact structure, we simulate the effects in networks with variable degree distributions. The infection attack rate can increase if the number of contacts per person is heterogeneous, implying the existence of high-degree individuals who are potential super-spreaders. The effectiveness of a socially targeted intervention suffers from heterogeneous contact patterns and depends on whether infection is predominantly transmitted to close or casual contacts. Our findings imply that the various contact networks' degree distributions as well as the allocation of contagiousness between close and casual contacts should be examined to identify appropriate strategies of disease control measures. PMID- 17288644 TI - Durability of antidepressant response to vagus nerve stimulation (VNS). AB - This study characterized the durability of improvement in patients who responded early or late while receiving vagus nerve stimulation (VNS). In both a pilot and pivotal study, patients were identified who had at least a 50% reduction in symptom scores 3 months (early responders) or 12 months (late responders) after starting VNS. Probabilities were determined for maintenance of response at 12 month and 24-month time-points. Consistency of improvement throughout the 24 month study period was evaluated, testing for change in serial depression ratings. In the pilot study, 30.5%, 23.7% and 45.8% were early responders, later responders, and non-responders, respectively. These rates were 14.6%, 19.5%, and 65.9% in the pivotal trial. The potential confound of alterations in antidepressant treatment was examined in the pivotal trial. In the pilot study, 72.2% and 61.1% of early responders (n=18) were responders at 12 and 24 months, respectively; 78.8% of late responders (n=14) were responders at 24 months. In the pivotal trial, of early responders (n=30), 63.3% and 76.7% maintained response at 12 and 24 months, respectively; of late responders (n=40), 65.0% maintained response at 24 months. Early and late responders had fewer changes in medication than non-responders across the pivotal study period. In both studies, analyses of serial depression ratings showed stable improvement in early and late responders. These samples had exceptional levels of chronicity and treatment resistance. Yet patients who showed substantial clinical benefit maintained the improvement at remarkably high rates. This durability of benefit was not attributable to alterations in other treatments. PMID- 17288645 TI - Mitochondrial DNA-dependent effects of valproate on mitochondrial calcium levels in transmitochondrial cybrids. AB - Calcium plays important roles in various cellular processes. Using transmitochondrial hybrid cells (cybrids) carrying fluorescent calcium indicators, we previously found two mitochondrial DNA (mtDNA) polymorphism sites, 8701 and 10398, that alter intracellular calcium signalling and mitochondrial pH. The 10398A polymorphism is reportedly associated with bipolar disorder, Parkinson's disease, Alzheimer's disease, and cancer, whereas 10398G is associated with longevity. In bipolar disorder, elevation of intracellular calcium levels in the platelets and lymphocytes is a well-replicated finding. Thus, we examined whether two mood stabilizers, lithium and valproate, affect the intracellular calcium signalling in cybrids with these mtDNA polymorphisms. After cybrids with 8701A/10398A and 8701G/10398G (three cell lines for each) derived from healthy controls were pretreated with lithium (0.75 mm or 1.5 mm) or valproate (0.6 mm or 1.2 mm) for 7 d, they were stimulated by 10 mum histamine. Valproate decreased mitochondrial calcium levels, compared with untreated cybrids, only in cybrids with 8701A/10398A. Moreover, valproate decreased cytosolic calcium levels at plateau after stimulation in cybrids with 8701A/10398A. These finding suggest that valproate may stabilize intracellular calcium only in cells with high mitochondrial calcium levels. PMID- 17288646 TI - Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness-persistence model. AB - BACKGROUND: Research suggests that low-grade psychotic experiences in the general population are a common but transitory developmental phenomenon. Using two independent general population samples, the hypothesis was examined that common, non-clinical developmental expression of psychosis may become abnormally persistent when synergistically combined with developmental exposures that may impact on behavioural and neurotransmitter sensitization such as cannabis, trauma and urbanicity. METHOD: The amount of synergism was estimated from the additive statistical interaction between baseline cannabis use, childhood trauma and urbanicity on the one hand, and baseline psychotic experiences on the other, in predicting 3-year follow-up psychotic experiences, using data from two large, longitudinal, random population samples from the Netherlands [The Netherlands Mental Health Survey and Incidence Study (NEMESIS)] and Germany [The Early Developmental Stages of Psychopathology (EDSP) study]. RESULTS: The 3-year persistence rates of psychotic experiences were low at 26% in NEMESIS and 31% in EDSP. However, persistence rates were progressively higher with greater baseline number of environmental exposures in predicting follow-up psychotic experiences (chi2=6.9, df=1, p=0.009 in NEMESIS and chi2=4.2, df=1, p=0.04 in EDSP). Between 21% and 83% (NEMESIS) and 29% and 51% (EDSP) of the subjects exposed to both environmental exposures and psychotic experiences at baseline had persistence of psychotic experiences at follow-up because of the synergistic action of the two factors. CONCLUSION: The findings suggest that environmental risks for psychosis act additively, and that the level of environmental risk combines synergistically with non-clinical developmental expression of psychosis to cause abnormal persistence and, eventually, need for care. PMID- 17288647 TI - The spectrum of suicidal ideation in Great Britain: comparisons across a 16-74 years age range. AB - BACKGROUND: Previous studies have examined suicidal ideation in older populations and emphasized the strong association with the presence of psychiatric disorder. However, associations with the presence of psychiatric disorder across the age range are unclear. Representative epidemiological estimates are needed. METHOD: In a national survey of psychiatric morbidity in Great Britain, 8580 randomly selected adults were interviewed. Three questions were asked to assess suicidal ideation, and psychiatric disorder was identified using the revised Clinical Interview Schedule (CIS-R). RESULTS: Suicidal ideation was up to three times commoner in younger adults than in those aged 55-74 years but the odds of depression in those with suicidal thoughts was significantly greater in the older age group (p<0.01). Tiredness with life (p<0.01) and thoughts of death (p<0.01) were also more strongly associated with depression in the older age group. Other major associations of suicidal ideation for all ages were: smaller social support group, being divorced or separated, poor self-rated general health, and limitations in activities of daily living (ADL). Being single was an important factor for younger age groups, and widowhood for older people. Life events were also important in younger people, but not in those aged 55-74 years. CONCLUSIONS: Suicidal thoughts and death wishes are comparatively more unusual in older people; however, they are more likely to be associated with clinical depression. In terms of suicide prevention this study emphasizes the importance of improving rates of recognition and treatment of depression in older people. PMID- 17288648 TI - Cerebral blood flow changes during retrieval of traumatic memories before and after psychotherapy: a SPECT study. AB - BACKGROUND: Traumatic memory is a key symptom in psychological trauma victims and may remain vivid for several years. Psychotherapy has shown that neither the psychopathological signs of trauma nor the expression of traumatic memories are static over time. However, few studies have investigated the neural substrates of psychotherapy-related symptom changes. METHOD: We studied 16 subthreshold post traumatic stress disorder (PTSD) subjects by using a script-driven symptom provocation paradigm adapted for single photon emission computed tomography (SPECT) that was read aloud during traumatic memory retrieval both before and after exposure-based and cognitive restructuring therapy. Their neural activity levels were compared with a control group comprising 11 waiting-list subthreshold PTSD patients, who were age- and profile-matched with the psychotherapy group. RESULTS: Significantly higher activity was observed in the parietal lobes, left hippocampus, thalamus and left prefrontal cortex during memory retrieval after psychotherapy. Positive correlations were found between activity changes in the left prefrontal cortex and left thalamus, and also between the left prefrontal cortex and left parietal lobe. CONCLUSIONS: Neural mechanisms involved in subthreshold PTSD may share neural similarities with those underlying the fragmented and non-verbal nature of traumatic memories in full PTSD. Moreover, psychotherapy may influence the development of a narrative pattern overlaying the declarative memory neural substrates. PMID- 17288650 TI - Human factors considerations in implementing telemedicine systems to accommodate older adults. AB - The number of older adults is increasing, and telemedicine has the potential to improve their access to health care. Telemedicine systems have been shown to benefit older adults by increasing peer support interactions, providing health care access to older adults in rural communities, reducing the cost of health care, increasing exercise, reducing pain and depression, and, perhaps most important, improving functional independence. However, older adults may have different needs from other users when interacting with telemedicine systems, because of age-related changes in perceptual, motor and cognitive abilities. The design of telemedicine technologies should, therefore, capitalize on older adults' strengths while minimizing their weaknesses. The field of human factors has much to offer in optimizing interactions between older adults and telemedicine technologies. Future research should take advantage of human factors methodologies to best design telemedicine technologies for an older population. PMID- 17288649 TI - Young males have a higher risk of developing schizophrenia: a Danish register study. AB - BACKGROUND: Gender differences are commonly reported in schizophrenia research, especially with regard to age at onset. Few studies have reported the age- and gender-specific incidence of schizophrenia in people aged up to 71 years, and no studies have reported the cumulative incidence of schizophrenia in people aged up to 71 years. METHOD: Two cohorts were established by linking data from the Danish Civil Registration System (DCRS) with data from the Danish Psychiatric Central Register (DPCR), which covers all incident cases of schizophrenia from 15 to 71 years. We estimated the gender- and age-specific incidence rates of schizophrenia for people aged up to 71 years. We also estimated the cumulative incidences. RESULTS: The incidence rates for males significantly exceeded those for females in the age range from 17 to 40 years. By their 72nd birthday, 1.59% of males and 1.17% of females had developed schizophrenia. CONCLUSION: Male sex is a major risk factor for the development of schizophrenia. PMID- 17288651 TI - Telemedicine for a Children's Field Hospital in Chechnya. AB - In 2001, the Children's Field Hospital in the Gudermes area of the Chechen Republic was connected to a telemedical centre at the Scientific Institute of Pediatrics and Children's Surgery in Moscow, via the Russian SCA HeliosNet satellite system. An asymmetric satellite link, in which there was a high-speed downlink from the satellite to Gudermes and a low-speed uplink from Gudermes to the satellite was used. In total, 179 teleconsultations were carried out from October 2001 until February 2002, when the field hospital was closed. Of the 179 teleconsultations, 26 were real-time, by videoconference and the rest were asynchronous, by email. Almost half of consultations were carried out for emergency or urgent reasons, thus demonstrating the value of providing access to the necessary experts. The use of satellite communication allowed telemedical support for medical decisions in a wide range of disease and trauma in children and teenage in a conflict situation. PMID- 17288652 TI - An economic analysis of the EHAS telemedicine system in Alto Amazonas. AB - Telemedicine systems providing voice communication and email by radio were installed at seven health centres (HCs) and 32 health posts (HPs) in the Alto Amazonas province of Peru during 2001. A cost analysis was performed to estimate the net effect on direct resource consumption from the perspective of society. Prior to the availability of the EHAS telemedicine system, there was a mean of 11.1 urgent patient referrals per year from the HPs and 14.0 referrals per year from the HCs. After the implementation of telemedicine, patient referrals fell to 2.5 per year from the HPs (P = 0.03) and to 8.4 per year from the HCs (P = 0.17). The net economic effect of the telemedicine programme over a four-year period was clearly positive, amounting to annual net savings of US$320,126 (using a 5% discounting rate). A one-way sensitivity analysis using a range of values for the discounting rate, and the number of urgent referrals, confirms that the programme was efficient (i.e. it made net financial savings) in all cases. From the restricted budgetary perspective of the health network, the results also demonstrate that the additional operational costs (telephone and maintenance) introduced by the telemedicine system were lower than the direct cost-savings produced for the health-care network. PMID- 17288653 TI - Post-surgical telehealth support for children and family care-givers. AB - Early discharge of children following surgery shifts the burden of care from professionals in hospital to family care-givers at home. We evaluated the relative effectiveness of telephone and videophone follow-up for children and families after a child's scoliosis surgery. Fourty-three patients and their families were enrolled in the study with 21 dyads receiving videophone and 22 dyads telephone support. At discharge, those in the intervention arm were provided with a videophone operating on the ordinary telephone network (PSTN). Data were gathered during telehealth contact on post-discharge day 3 and during extra calls with the clinic nurse, and during sessions with a research assistant comprising a follow-up call and an interview at the six-week post-surgical visit. Calls and interviews were recorded and transcribed. Data were analysed using constant comparative analysis. The results showed that videophone and telephone use provided care continuity for patients and their families following a child's back surgery. The relative effect of the videophone and telephone technology depended on the fit between the characteristics of the patients and families and the capacities of the technology. When implementing telehealth for follow-up care, a participatory process is recommended to ensure a fit between user characteristics and technology. PMID- 17288654 TI - Remote patient-provider communication and quality of life: empirical test of a dialogic model of cancer care. AB - We examined the feasibility of a Cancer Care Dialogues Model, with daily telehealth interactions between patients at home and their care coordinator, who acted as an adjunct to the oncologist. The patient and the care coordinator used a home messaging device, connected via the ordinary telephone network. Thirty four patients with a new diagnosis of cancer and whose treatment plan included chemotherapy taken at a single clinic were enrolled and followed for six months. The home messaging device collected information daily on common symptoms associated with chemotherapy. On average, the patients had the home messaging device for 120 days (range 30-180). The mean cooperation rate was 84% (range 4 100). No variables were significantly associated with patient cooperation in the dialogues over time. The health-related quality of life (HRQL) mean score at baseline was 73.9 (SD 15.4), and the mean score at six months was 78.4 (SD 14.5). After adjusting for demographic and clinical factors, there was a 6.5-point increase in HRQL score between the baseline and end of treatment, which represented an important clinical difference. Management of nervousness/worry over time through cancer care dialogues is important in maintaining HRQL and can be assisted by remote home messaging. PMID- 17288656 TI - Implementation and evaluation of a low-cost telemedicine station in the remote Ecuadorian rainforest. AB - A clinical workstation was developed to provide basic telemedicine services in a medical clinic in rural Ecuador. The unit cost was less than $1000. The system provided videoconferencing and a Spanish language electronic medical record (EMR) for clinic consultations. All partners participated in the development of the EMR. Over a six-month period, almost all new patient encounters and ultrasound studies were entered into the EMR. Of 2387 patient encounters, 572 were recorded in electronic format and 80% were transmitted over the Internet for consultation. Four hundred and eight ultrasound studies were filed with the EMR and 90% were transmitted over the Internet for shared evaluation. During the six months of the study, there were no serious software or hardware problems. The doctor in Ecuador was initially trained at the laboratory in the USA. The two sites were in contact by email almost daily. Without such interaction, the performance of the software and hardware would probably have been worse. When a structured programme of instruction, protocols, EMR and technology support is in place, telemedicine can support remote rural practice. PMID- 17288655 TI - Store-and-forward teledermatology results in similar clinical outcomes to conventional clinic-based care. AB - We compared the clinical outcomes after store-and-forward teledermatology with those following conventional clinic-based consultation. Subjects were randomized to either usual care (a conventional clinic-based dermatology appointment) or a store-and-forward teledermatology consultation. All subjects received baseline digital imaging and re-imaging was performed four months later. A total of 776 subjects were approached for inclusion, and a total of 508 image sets were reviewed, 236 in usual care and 272 in teledermatology. The image sets from both study arms were used to make clinical outcome assessments between baseline and four months. A dermatologist who was blinded to the randomization rated the clinical outcomes using a three-point clinical course rating scale (1 = improved, 2 = no change, 3 = worse). In the usual care group, 65% were rated as 'improved', 32% were rated as 'no change' and 3% were rated as 'worse'. For teledermatology, 64% were rated as 'improved', 33% as 'no change' and 4% as 'worse'. The results of the study indicate that store-and-forward teledermatology consultations produce similar clinical outcomes when compared with conventional clinic-based consultations. PMID- 17288657 TI - Perception of eye contact in video teleconsultation. AB - During patient consultations by videoconferencing, clinicians often sit as close as 1 m from the videoconferencing units, creating a significant eye gaze angle (i.e. the angle between the eye and the camera, and the eye and the centre of the display). Eye gaze angle may adversely affect the satisfaction with videoconferencing. Four videoconferencing environments were examined: desktop PC, portable telehealth unit, videoconferencing room, and a boardroom equipped with a ceiling-mounted camera and a projection screen. Two still images of each of the three subjects were captured: one at a 7 degrees eye gaze angle and the other at 15 degrees. Each of 53 observers ranked four pairs of images for each of the three subjects. In 87% of cases, the observers perceived better eye contact at an eye gaze angle of 7 degrees than 15 degrees. Also, 92% of observers responded that the difference in the perceived eye contact was important to them as patients. Improved eye contact can be realized by increasing the horizontal distance of participants from the videoconferencing unit. PMID- 17288658 TI - Equivalence of functional communication assessment in speech pathology using videoconferencing. AB - We examined the equivalence of videoconferencing assessment of communication by speech-language pathologists (SLPs). Using a randomized, double-crossover agreement study, 24 post-stroke patients were randomized to a remote or face-to face administration of a subset of the Boston Diagnostic Aphasia Examination and to remote or face-to-face assessment of speech comprehension, speech expression and motor speech. The videoconferencing equipment was operated at a transmission speed of 384 kbit/s. Each patient was simultaneously scored by both the face-to face and the remote SLPs. SLPs were blind to each other's results. Percentage agreement within the 95% limits of agreement ranged from 92% to 100% for each functional communication measure, regardless of assessment site and administration of the aphasia examination. The results suggest that assessment of a patient's functional communication using videoconferencing is equivalent to a face-to-face encounter. PMID- 17288659 TI - Home telecare during intensive insulin treatment--metabolic control does not improve as much as expected. AB - We examined the influence of the increased frequency of data reporting on metabolic control in patients with diabetes. Data reporting was via a home telecare system that stored blood glucose values and was integrated with a simple electronic logbook. The data collected by the patient were automatically transmitted via the telephone network every night. The study population consisted of 30 patients with type I diabetes, who were randomly allocated to the home telecare group or the control group. The control group was treated based on clinical examinations performed every three weeks. In the home telecare group, the patient-collected data were transmitted to hospital daily, enabling more frequent interventions by the doctor. The average study period was 180 days (SD 22) in the home telecare group and 176 days (SD 16) in the control group. The mean level of metabolic control and the insulin dose adjustment patterns were very similar in both groups regardless of the much higher (15 times) reporting frequency in the home telecare group. The patient-collected data were not fully utilized, mainly because of too high within-day variability in glycaemic control and the high workload connected with daily data analysis. PMID- 17288660 TI - Electrocardiogram transmission using GSM multimedia message service. PMID- 17288664 TI - The Cardiff dental study: a 20-year critical evaluation of the psychological health gain from orthodontic treatment. AB - OBJECTIVES: Despite the widespread belief that orthodontics improves psychological well-being and self-esteem, there is little objective evidence to support this (Kenealy et al., 1989a; Shaw, O'Brien, Richmond, & Brook, 1991). A 20 year follow-up study compared the dental and psychosocial status of individuals who received, or did not receive, orthodontics as teenagers. DESIGN: A prospective longitudinal cohort design with four studies of the effect of orthodontic treatment. Secondary analysis of outcome data incorporated orthodontic need at baseline and treatment received in a 2 x 2 factorial design. METHODS: A multidisciplinary research programme studied a cohort of 1,018, 11-12 year old participants in 1981. Extensive assessment of dental health and psychosocial well-being was conducted; facial and dental photographs and plaster casts of dentition were obtained and rated for attractiveness and pre-treatment need. No recommendations about orthodontic treatment were made, and an observational approach was adopted. At the third follow-up 337 (30-31 year olds) were re-examined in 2001. RESULTS: Participants with a prior need for orthodontic treatment as children who obtained treatment demonstrated better tooth alignment and satisfaction. However when self-esteem at baseline was controlled for, orthodontics had little positive impact on psychological health and quality of life in adulthood. Lack of orthodontic treatment where there was a prior need did not lead to psychological difficulties in later life. Dental status alone was a weak predictor of self-esteem at outcome explaining 8% of the variance. Self esteem in adulthood was more strongly predicted (65% of the variance) by psychological variables at outcome: perception of quality of life, life satisfaction, self-efficacy, depression, social anxiety, emotional health, and by self-perception of attractiveness. CONCLUSIONS: Longitudinal analysis revealed that the observed effect of orthodontic treatment on self esteem at outcome was accounted for by self esteem at baseline. Prior need for treatment assessed in childhood made a small contribution to the prediction of self-esteem 20 years later in adulthood. Dental status in adulthood, whilst statistically significant, appeared to be of minor importance in a model that included other psychological variables. When prior need for treatment was taken into account there was little objective evidence to support the assumption that orthodontics improves long-term psychological health. PMID- 17288663 TI - Trajectories of recovery of quality of life in women after an acute cardiac event. AB - OBJECTIVES: Female cardiac patients' health-related quality of life (HRQoL) during the first year after an acute cardiac event was compared with age-weighted Australian population norms. The impact of age, event type and cardiac rehabilitation (CR) programme attendance on recovery was assessed. METHODS: The short form 36-item health survey (SF-36) was administered to 229 women aged from 36 to 84 years consecutively admitted to 4 hospitals after acute myocardial infarction (AMI) or to undergo coronary artery bypass graft surgery (CABGS). Data were collected at 4 time points over 12 months. SF-36 subscale scores were compared with age-weighted norms for Australian women. Mplus was used to analyse growth trajectories for SF-36 subscales. RESULTS: Patients had impaired HRQoL at baseline (except in general health), with progressive improvement over time. Recovery to normative levels was fastest in the areas of bodily pain and mental health (by 2 months) and slowest in the area of physical functioning, and physical and emotional role limitations (by 12 months). By 4 months, general health scores had surpassed population norms. For all scales, most improvement occurred in the first 2 months, with little subsequent improvement. CABGS patients showed significantly more improvement than AMI patients in several areas, partly due to the poorer functioning of CABGS patients at baseline. Rate of improvement was not influenced by patients' age or frequency of CR attendance. CONCLUSIONS: Impairment of HRQoL in female cardiac patients is most pronounced at the time of the event, with most recovery occurring during early convalescence and full recovery in all domains by 12 months post-event. PMID- 17288665 TI - Gender power imbalance and differential psychosocial correlates of intended condom use among male and female adolescents from Venda, South Africa. AB - OBJECTIVES: In South Africa, a gender power imbalance exists which may prevent women from negotiating safe sexual encounters. In this study we tested which constructs from Protection Motivation Theory (PMT) and the Theory of Planned Behavior (TPB) under these circumstances were most related to condom use intention. We hypothesized that in a situation of gender power imbalance self efficacy would be a more salient correlate of intended condom use for females, while for males attitude to condoms and subjective norm would be more important. DESIGN: This study employed a cross-sectional questionnaire design. METHOD: Male participants (N=94) and female participants (N=101) from Venda, South Africa completed standard, multi-item, reliable measures of TPB constructs (condom related attitude, subjective norm, perceived behavioural control, intention) and PMT constructs (vulnerability, severity, fear, response-efficacy, self-efficacy) and reported their past condom use behaviour. RESULTS: Regression analysis indicated that among males attitude to condoms and subjective norm were significantly related to intended condom use. Among females attitude and self efficacy were significantly related to intended condom use. CONCLUSION: The findings indicate that in a situation of gender power imbalance psychosocial correlates of intended condom use differ for males and females. Gender-specific analysis of determinants of condom use may be more appropriate in a situation of gender power imbalance. PMID- 17288666 TI - Physical and psychological sequelae of critical illness. AB - OBJECTIVES: To measure levels of anxiety, depression and post-traumatic stress among survivors of a critical illness and to relate these symptoms to general health parameters. DESIGN: A prospective study of patients who had spent a minimum 3 days (median 9 days) in a general intensive care unit (ICU). Of these patients, 51 were interviewed 3 months after discharge and 45 of them were reviewed at 9 months. METHODS: General health was assessed by a physical symptom score, the EuroQol 'thermometer' and the Short Form 36 (SF-36) questionnaire. Physical and mental component summary measures (PCS, MCS) were calculated from the SF-36 data. Psychological health was assessed using both the Hospital Anxiety and Depression Scale and the Impact of Events Scale. RESULTS: At both 3 and 9 months after ICU discharge 24% of patients qualified as a 'case' of anxiety, while similar figures were seen for intrusion (24 and 20%). The incidence of depression (35 and 47%) and avoidance (36 and 38%) was higher on each occasion. Four of the eight SF-36 domains improved with time, as did PCS (from 29.0 to 35.4), but there was no significant difference in physical symptom score, EuroQol value or MCS. Strong correlations were seen between the physical and psychological parameters at each time point. CONCLUSIONS: A substantial proportion of patients who survive a critical illness show evidence of anxiety and depression up to 9 months later, and most of them also have symptoms indicative of post-traumatic stress. Delayed physical recovery may contribute to this psychological morbidity. ICU follow-up clinics should be able to detect patients suitable for psychological intervention. PMID- 17288667 TI - The influence of diabetes upon adolescent and young adult development: a qualitative study. AB - It is not clear how developmentally appropriate healthcare services for adolescents (11-15) and young adults (16-25) should be provided. AIMS: First, to describe and understand the influence of diabetes upon psychosocial development and second, to highlight the implications for healthcare teams. DESIGN: Given the heterogeneity of findings, lack of conceptual clarity and lack of quantitative measures, qualitative semi-structured interviews were used, to define more clearly the constructs significant to young people. METHODS: People aged 16-25 registered with one secondary care diabetes service, across two districts in north-east England were contacted. Nineteen interviews were conducted and analysed using a Framework Approach. RESULTS: Diabetes can impact upon personal identity and self-concept. Peer support can buffer from negative effects, especially if young people control the disclosure of their diabetes. In coming to rely more on peers, participants continue to value the safe base of their family, especially at times of change and challenge. A key challenge appears to be coming to terms with risk and mortality. CONCLUSIONS: Health care services need to support young people with self-care but must also understand and respond to the social and personal complexities of growing-up with a long-term health condition. Psychologists may have a role in promoting and supporting such an approach. PMID- 17288668 TI - Are beliefs elicited biased by question order? A theory of planned behaviour belief elicitation study about walking in the UK general population. AB - OBJECTIVES: To elicit salient beliefs about walking for an average of 30 minutes per day, with the aims of investigating whether the order of Theory of Planned Behaviour (TPB) belief elicitation questions affects the number and types of beliefs elicited and whether affective and instrumental questions elicit different beliefs. DESIGN: A 3 x 2 x 2 x 2 mixed factorial design was employed, with order of behavioural, normative and control questions, and affective and instrumental questions as between-subjects variables, and affective/instrumental and positive/negative questions as within-subjects variables. METHOD: Quota sampling with regards to age and gender (N=180) was employed to obtain a sample that was broadly representative of the adult general population. RESULTS: The order in which behavioural, normative and control beliefs were asked had little impact on the number or type of beliefs elicited. The affective/instrumental attitude distinction was supported. Few differences were apparent between older and younger respondents and between men and women. CONCLUSION: TPB belief elicitation studies are not biased by order effects. Interventions to promote walking should consider targeting affective beliefs, e.g. stress relief, in addition to beliefs about health, which is the traditional focus of health campaigns. Given the similarities in beliefs across demographic groups, 'one size fits all' interventions to promote walking are appropriate. PMID- 17288669 TI - A comparison of writing exercises to motivate young women to practise breast self examinations. AB - OBJECTIVES: This study investigated the novel use of written emotional disclosure procedures for motivating health behavior change, specifically engagement in breast self examination (BSE) among college-aged women. Writing instructions were tailored to a precontemplative stage of change in accordance with the transtheoretical model proposed by Prochaska and DiClemente (1983) to test the hypothesis that stage-matched writing strategy would facilitate greater contemplation than a stage-mismatched writing strategy and a control condition. DESIGN AND METHODS: Precontemplative women (N=55) were randomly assigned to one of three groups: (a) a stage-matched consciousness-raising writing exercise; (b) a stage-mismatched BSE action-oriented exercise; or (c) a control condition, and measured on contemplation, preparation, and action, as well as performance of BSEs. RESULTS: Analyses indicated that both the consciousness-raising writing exercise and the BSE action-oriented exercise increased participants' level of contemplation when compared to the control condition. Women assigned to the BSE action-oriented exercise endorsed more statements indicative of an action stage of change and exhibited a trend for greater performance of BSE compared to the other two conditions. CONCLUSIONS: The application of writing exercises and the relevance of stage-matching is discussed in the context of the stage of change model. PMID- 17288670 TI - Predicting stress in pre-registration nursing students. AB - OBJECTIVE: To determine which variables from a pool of potential predictors predict General Health Questionnaire 'caseness' in pre-registration nursing students. DESIGN: Cross-sectional survey, utilizing self-report measures of sources of stress, stress (psychological distress) and coping, together with pertinent demographic measures such as sex, ethnicity, educational programme and nursing specialty being pursued, and age, social class and highest qualifications on entry to the programme. METHODS: Questionnaire packs were distributed to all pre-registration nursing students (N=1,362) in a large English university. Completed packs were coded, entered into statistical software and subjected to a series of logistic regression analyses. RESULTS: Of the questionnaire packs 1,005 (74%) were returned, of which up to 973 were available for the regression analyses undertaken. Four logistic regression models were considered and, on the principle of parsimony, a single model was chosen for discussion. This model suggested that the key predictors of caseness in the population studied were self report of pressure, whether or not respondents had children (specifically, whether these children were pre-school or school-age), scores on a 'personal problems' scale and the type of coping employed. The overall caseness rate among the population was around one-third. CONCLUSIONS: Since self-report and personal, rather than academic, concerns predict stress, personal teachers need to play a key role in supporting students through 'active listening', especially when students self-report high levels of stress and where personal/social problems are evident. The work-life balance of students, especially those with child-care responsibilities, should be a central tenet in curriculum design in nurse education (and, indeed, the education of other professional and occupational groups). There may be some benefit in offering stress management (coping skills) training to nursing students and, indeed, students of other disciplines. PMID- 17288671 TI - Domestic dogs and human health: an overview. AB - PURPOSE: The domestic dog is one of the most commonly owned, and widely utilized, animals in today's society. This paper provides an overview of research that has explored the relationship between the domestic dog and human well-being. METHODS: The article initially concentrates on the value of dogs for physical health in humans, exploring the evidence that this species can prevent us from becoming ill, facilitate our recovery from ill-health, and even serve as an early warning system for certain types of underlying ailment including cancer, oncoming seizures and hypoglycaemia. The paper then examines the relationship between dogs and psychological health in humans, exploring the ability of this species to aid the disabled and serve as a therapist to those in institutional settings such as hospitals, residential homes and prisons. Weaknesses in the existing research in this area are highlighted throughout the article. CONCLUSIONS: Taken together, the studies reviewed suggest that dogs can have prophylactic and therapeutic value for people. PMID- 17288677 TI - Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial. AB - OBJECTIVE: This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10 mg/day with sertraline optimally dosed within its recommended dose range (50-200 mg/day) for the treatment of major depressive disorder. METHODS: In this multicenter trial, depressed patients (DSM-IV defined; baseline Montgomery-Asberg Depression Rating Scale [MADRS] 22) aged 18-80 years were randomly assigned to 8 weeks of double-blind treatment with escitalopram (10 mg/day) or sertraline (50-200 mg/day) following a 1-week single-blind placebo lead-in period. There was no placebo comparison arm. Sertraline was initiated at 50 mg/day, and could be increased by 50 mg/day at weekly intervals based on clinical need and tolerability at the lower dose level. The blind was maintained with matching double-blind placebo capsules for the escitalopram group. Change from baseline to endpoint in MADRS total score (last observation carried forward) was the primary efficacy measure. RESULTS: A total of 212 patients received double-blind medication. At week 8, the mean sertraline dosage was 144 mg/day (median = 150 mg/day). Mean changes from baseline to endpoint in MADRS scores were -19.1 and -18.4 for the escitalopram and sertraline groups, respectively. At endpoint, 75% and 70% of escitalopram- and sertraline-treated patients, respectively, were responders (> or =50% improvement from baseline in mean MADRS scores). Both treatments were generally well tolerated; only 2% and 4% of patients prematurely discontinued escitalopram and sertraline treatment, respectively, due to adverse events. CONCLUSION: No differences in efficacy were observed for fixed-dose escitalopram 10 mg/day and sertraline flexibly dosed from 50-200 mg/day. At these doses, both escitalopram and sertraline were generally well tolerated. PMID- 17288678 TI - Cost-utility comparison of escitalopram and sertraline in the treatment of major depressive disorder. AB - OBJECTIVE: To construct a cost-utility model comparing escitalopram with sertraline in the treatment of major depressive disorders. METHODS: A decision analytic model was created to compare the cost-utility of these two antidepressants from the perspective of a managed-care organization. The model was designed to compare 10-20 mg/day of escitalopram to 50-200 mg/day of sertraline. Benefits (utility) scores were calculated based on clinical and utility data obtained from the literature. Direct medical costs included costs of the antidepressants, titration, treatment failures, and adverse events. Costs and benefits were modeled for a 6-month period and the model was subjected to thorough sensitivity analyses. RESULTS: The estimated 6-month total cost was 919 dollars for escitalopram and 1351 dollars for sertraline. The estimated QALYs were 0.40296 for escitalopram and 0.39268 for sertraline. These differences were mostly due to differences in drug acquisition costs and adverse events. The robustness of the cost-utility model results were tested in a Monte Carlo simulation of 10 000 patients and it indicated an 88.5% probability that escitalopram was the dominant therapy, suggesting both lower costs and greater QALYs. CONCLUSION: This cost-utility model that incorporated the costs of titration and impact of side-effects comparing escitalopram 10-20 mg per day and sertraline 50-200 mg per day shows that escitalopram appeared to be less costly and produced efficacy (utility) at least as good as and maybe slightly better than that of sertraline. PMID- 17288679 TI - Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy. AB - OBJECTIVE: To compare blood pressure response and antihypertensive medication use visit-by-visit from baseline in patients receiving losartan-based or atenolol based therapy in the LIFE study. RESEARCH DESIGN: LIFE was a randomized, double blind trial comparing losartan-based and atenolol-based treatment regimens on the primary composite endpoint of death, myocardial infarction (MI), or stroke in 9193 patients aged 55-80 years with hypertension and left ventricular hypertrophy. Systolic and diastolic, pulse, and mean arterial pressures, blood pressure responder rates, distribution of open-label antihypertensive agents utilized, and the proportion of patients on randomized treatment were determined for each group at each clinic visit over a follow-up period of at least 4 years. RESULTS: Overall blood pressure reductions were comparable in the losartan-based and atenolol-based treatment groups. The mean reductions in sitting trough systolic and diastolic blood pressures from baseline to the end of follow-up (or last visit before a primary endpoint event) were 30.2/16.6 mmHg in the losartan group and 29.1/16.8 mmHg in the atenolol group. The time-averaged difference in overall mean arterial pressure was similar between groups. The proportion of patients on individual dose combinations varied visit by visit but was generally comparable between groups. During the entire study, 56% (2579/4605) of losartan treated patients received at least one dose of the combination of losartan 100 mg plus hydrochlorothiazide 12.5 mg and 51% of atenolol-treated patients received 100 mg of atenolol plus hydrochlorothiazide 12.5 mg at some time during the study. CONCLUSIONS: Differences in blood pressure or distribution of add-on medications between treatment groups were not evident in the LIFE trial and, thus, cannot account for the observed outcome difference in the primary endpoint of risk reduction of the composite of cardiovascular death, stroke and MI favoring losartan. PMID- 17288680 TI - ESPRIT study design and outcomes--a critical appraisal. AB - Evidence is needed to guide therapeutic decisions on patients who had ischaemic cerebral events. The recently published European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), an open-label randomised controlled study, compared long-term treatment of patients randomised to aspirin 30-325 mg daily with (n = 1363) or without (n = 1376) dipyridamole 200 mg twice daily. The study found the combination to be superior to aspirin alone (13% vs. 16% events in a composite endpoint of vascular death, non-fatal stroke, non-fatal myocardial infarction, or major bleeding; hazard ratio 0.8; 95% confidence interval 0.66 0.98). In the interpretation of the results, criticism has been raised related to the study design (open-label, change during the study), the study conduct (half of the aspirin patients underdosed, 33% drop-out rate in the combination group, missing information on potential confounders such as protective concomitant medication), and the outcomes (lack of differences in the efficacy outcomes between the intent-to-treat and the on-treatment populations, lack of differences in minor bleedings between treatment groups, borderline statistical significance of primary study endpoint). Further studies are needed to determine the place of aspirin/dipyridamole combinations in the secondary prevention of stroke. PMID- 17288681 TI - Pharmacokinetic model and simulations of dose conversion from immediate- to extended-release tramadol. AB - OBJECTIVE: Extended-release tramadol (tramadol ER) is a once-daily formulation of tramadol approved in the United States for moderate to moderately severe chronic pain in adults. This modeling and simulation analysis was conducted to support dosing recommendations for switching patients receiving immediate-release tramadol (tramadol IR) to tramadol ER. RESEARCH DESIGN AND METHODS: Monte Carlo simulations based on steady-state data from three Phase 1 studies predicted minimum plasma concentration (C(min)), maximum plasma concentration (C(max)), and area under the plasma-concentration-versus-time curve (AUC). MAIN OUTCOME MEASURES: Pharmacokinetic parameters were compared between 100-mg daily increments of tramadol ER every 24 h (Q24H) and corresponding 25-mg increments of tramadol IR every 6 h (Q6H), such as tramadol ER 200 mg Q24H versus tramadol IR 200, 225, 250, and 275 mg daily. RESULTS: Tramadol ER and IR were predicted to provide similar exposure (AUC) at a total daily dose of 100, 200, or 300 mg. Estimated exposure was comparable between tramadol IR 125-, 225-, and 325-mg and tramadol ER 100-, 200-, and 300-mg, respectively. Estimated exposure was 30-41% lower with tramadol ER 100 mg versus tramadol IR 150 and 175 mg daily, 15-26% lower with tramadol ER 200 mg versus tramadol IR 250 and 275 mg daily, and 8-19% lower with tramadol ER 300 mg versus tramadol IR 350 and 375 mg daily. CONCLUSIONS: This pharmacokinetic analysis supports switching patients from a total daily dose of tramadol IR 200 or 300 mg directly to tramadol ER 200 and 300 mg once daily, respectively. Patients who take other doses of tramadol IR may switch to the next lower 100-mg increment of tramadol ER (e.g., from tramadol IR 225, 250, or 275 mg daily in divided doses to tramadol ER 200 mg once daily). Confirmation of these findings would require clinical studies comparing the systemic exposure of tramadol upon switching from the IR to the ER formulation. PMID- 17288682 TI - Treatment options for patients with suboptimal response to surgery for stress urinary incontinence. AB - BACKGROUND: Many women with stress urinary incontinence (SUI) undergo surgery to relieve their symptoms. Currently, tension-free vaginal tape or transobturator tape sling procedures are the surgical treatments of choice. Although these procedures are often successful, a growing number of women experience suboptimal results ranging from improvement without cure to postoperative failure. Follow-up surgery often improves residual or recurrent symptoms but generally carries lower success rates and higher complication risks. Additionally, many women with suboptimal results are reluctant to undergo further surgery. SCOPE: A PubMed literature search for studies of SUI treatment options published from 1986 to 2006 was performed. FINDINGS: The literature revealed a gap in published studies addressing non-surgical options for patients with failed SUI surgeries. Studies of non-surgical treatments for SUI often exclude women who have had prior surgeries, or do not analyze this subgroup. It is, therefore, difficult to assess non-surgical treatment options for women with failed surgeries. Women whose residual or recurring SUI is attributable to intrinsic sphincter deficiency may instead elect the injection of a bulking agent. Bulking agents are associated with a low rate of complications but frequently require several injections to be successful. Women experiencing suboptimal surgical results whose SUI is attributable to hypermobility may select a new non-surgical treatment, radiofrequency collagen denaturation. This non-invasive procedure has also demonstrated a low rate of complications. CONCLUSIONS: Considering the effect of SUI symptoms on women's quality of life, and with more women experiencing suboptimal results after surgery for SUI, it is important to assess alternatives to further surgery. PMID- 17288683 TI - An analysis of which anti-osteoporosis therapeutic regimen would improve compliance in a population of elderly adults. AB - OBJECTIVE: Although medications to prevent osteoporotic fractures have been proven to be effective, compliance to these therapies is generally poor. Therapeutic regimens for different anti-osteoporotic medications differ widely and it is currently unknown which regimen would be most preferred by patients. RESEARCH DESIGN AND METHODS: We conducted a large, population-based study to discern which therapeutic attributes would be most preferable to a population representative of the age and sex distribution of patients with osteoporosis. RESULTS: Our study sample was restricted to persons aged 55 years and over and comprised 2485 individuals (mean age of 64.5 years). The study population was predominantly female (90.3%) and two-thirds of the respondents reported current daily medication use. Nearly half (45%) of the study population preferred to take medications daily, while one in five preferred weekly therapy and 30% preferred monthly therapy (p < 0.0001 for between proportion comparisons). When given the option of choosing between three different medication regimen scenarios, those subjects not currently using anti-osteoporotic medications preferred a theoretical regimen which was daily and did not involve subsequent fasting and maintaining an upright posture. CONCLUSIONS: Our data suggest that compliance with osteoporotic medications could be improved if patients are able to choose a therapeutic regimen best suited to their particular needs. The majority of subjects preferred a drug which was taken daily and with minimal inconvenience, rather than a weekly drug with slightly more inconvenience. Given that most physicians currently prescribe anti-osteoporotic therapy as a weekly regimen, at the time of diagnosis physicians should ascertain which regimen would be most preferable to patients prior to initiating therapy. PMID- 17288684 TI - Mistiming of intercourse as a primary cause of failure to conceive: results of a survey on use of a home-use fertility monitor. AB - OBJECTIVE: To assess demographics, fecundity characteristics and fertility history of couples who successfully conceived using a home-use Fertility Monitor. STUDY DESIGN: This was a retrospective US observational study of couples who successfully conceived using a Fertility Monitor. Data were self-reported by volunteers using a questionnaire supplied and collected by mail. Of 276 surveys distributed, 196 (71.0%) were returned and evaluated. RESULTS: Length of time trying to conceive was < 12 months for 70% of women; proportions were similar across age groupings. After switching to the Fertility Monitor, 49.5% and 91.9% of women had conceived within first and third cycles, respectively. Prior to Fertility Monitor use, conception aids were used by 84.2% and 64.3% had consulted a physician to seek help in attempting to conceive. Average costs of prior treatment were (in US dollars) 6637 dollars; median costs for infertility evaluation were 1075 dollars per cycle. Fertility Monitor costs ranged from 250 dollars for one cycle to 550 dollars after 10 cycles. CONCLUSIONS: A probable cause for failure to conceive appeared to be mistiming of intercourse. The issue of early intervention with tests and medications were highlighted, resulting in escalating costs and strain on the couple. The use of a home Fertility Monitor that identifies all fertile days of the cycle and allows couples to target intercourse accordingly, should be considered as an alternative choice for couples seeking to conceive during the first year, before other attempts at infertility diagnosis are made, unless there are conflicting clinical reasons. PMID- 17288685 TI - Epoetin delta, erythropoietin produced in a human cell line, in the management of anaemia in predialysis chronic kidney disease patients. AB - OBJECTIVE: To demonstrate safety and efficacy of epoetin delta for the management of anaemia in predialysis patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: This was a multicentre, open-label, uncontrolled study with predialysis CKD patients who had previously received subcutaneous epoetin therapy. Patients were switched to epoetin delta from their previous therapy, at an identical dose. Dose was subsequently titrated to maintain haemoglobin at 10.0 12.0 g/dL. Study duration was 52 weeks. MAIN OUTCOME MEASURES: The primary endpoint was average haemoglobin levels over Weeks 12, 16, 20 and 24. Secondary analyses were performed on the proportion of patients with haemoglobin and haematocrit levels over preset target levels, haemoglobin and haematocrit levels through to study end and dosing levels. RESULTS: Haemoglobin levels were maintained at 11.3 +/- 1.2 g/dL over Weeks 12-24. Over 80% of the haemoglobin measurements and 95% of the haematocrit measurements were above the predefined target level (haemoglobin > or = 10 g/dL; haematocrit > or = 30%). Weekly dose levels did not change significantly over the course of the trial. Epoetin delta was well tolerated, with adverse events occurring at frequencies expected for this patient population; no patient developed neutralizing anti-erythropoietin antibodies. CONCLUSIONS: Epoetin delta was an effective and well-tolerated agent for the management of anaemia in a subgroup of predialysis CKD patients. PMID- 17288686 TI - Effects of desloratadine and alcohol coadministration on psychomotor performance. AB - OBJECTIVE: This study was set up to evaluate the effects of desloratadine 7.5 mg daily, with and without alcohol, on sedation and psychomotor performance. RESEARCH METHODS: In a double-blind, placebo-controlled, four-way crossover trial, 25 adult patients were randomized to desloratadine 7.5 mg, desloratadine 7.5 mg plus alcohol, placebo, or placebo plus alcohol. Alcohol was weight adjusted to an average blood alcohol concentration of 0.1%. Assessments included the modified Romberg test, Stanford Sleepiness Scale, Digit Symbol Substitution Test, Serial Add Subtract Reaction Time Test, and the Psychomotor Vigilance Test. The primary variable was the mean score of each of the five tests averaged over the treatment period, expressed as the mean percent change from baseline. RESULTS: Across these assessments, differences between desloratadine alone or with alcohol versus placebo alone or without alcohol, were not significant, whereas most differences between desloratadine and placebo alone versus desloratadine and placebo with alcohol were significant (p < 0.01). Thus, with or without alcohol, desloratadine 7.5 mg does not increase sedation or impair psychomotor performance. Most adverse events (AEs) were mild-to-moderate in severity, with the most frequently reported individual AEs being headache, fatigue, nausea, vomiting, and dry mouth. The study does have potential limitations. The measures used are restricted to a particular profile of the known effects of alcohol only, and the relatively high doses of alcohol used alone demonstrate effects on psychomotor function and attention. CONCLUSIONS: A single dose of desloratadine does not potentiate alcohol-mediated CNS impairment. Desloratadine alone or in combination with alcohol was safe and well tolerated. PMID- 17288687 TI - Treatment of acute bronchitis with a liquid herbal drug preparation from Pelargonium sidoides (EPs 7630): a randomised, double-blind, placebo-controlled, multicentre study. AB - OBJECTIVE: The objective of this study was to examine the efficacy and safety of a herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) in the treatment of acute bronchitis in adults outside the very restricted indication for an antibiotic therapy. RESEARCH DESIGN AND METHODS: This was a randomised, double-blind, placebo-controlled, multicentre study with 217 patients aged between 18 and 66 years with acute bronchitis. One hundred and eight patients were given 30 drops of EPs 7630-solution three times daily and 109 patients 30 drops of placebo three times daily for a period of 7 days. MAIN OUTCOME MEASURES: Individual change in bronchitis symptom score (BSS) over 7 days, individual symptoms, patient satisfaction and adverse events. RESULTS: After 7 days of treatment, the BSS decreased by 7.6 +/- 2.2 points in the EPs 7630 group and by 5.3 +/- 3.2 points in the placebo group. The 95% confidence interval for the difference between the effects was calculated as 1.6-3.1, showing highly significant superiority for the EPs 7630 treatment (p < 0.0001). There were also marked improvements in the individual symptoms, which are the components of BSS - cough, chest pain on coughing, sputum, rales/rhonchi and dyspnoea - in the treatment group, relative to placebo. Patient satisfaction was very good. Only minor and transitory adverse events were recorded. No serious adverse events occurred during the trial. CONCLUSION: EPs 7630-solution is a well tolerated and effective treatment for acute bronchitis in adults outside the very restricted indication for an antibiotic therapy. PMID- 17288688 TI - Quetiapine augmentation of treatment-resistant depression: a comparison with lithium. AB - OBJECTIVE: The prevalence of and morbidity associated with treatment-resistant depression has motivated the exploration of treatment alternatives. In this study, quetiapine was compared with lithium in the augmentation of treatment resistant depression. RESEARCH DESIGN AND METHODS: Open-label, comparative study in 20 patients with major depression who had failed to respond after 4 weeks of treatment with an antidepressant at the maximal recommended dose. Patients were randomised to either lithium or quetiapine in addition to the maximally dosed antidepressant and any other concurrent medications. Lithium was initiated at 600 mg/day; quetiapine was titrated to 400 mg by day 7. RESULTS: Depression, measured by the Hamilton Depression Rating Scale (HAM-D), significantly improved from baseline in both quetiapine (F(1,90) = 25.11, p < 0.0001) and lithium (F(1,90) = 34.54, p < 0.0001). The difference in improvement between the two groups began at day 14 and was seen at all timepoints thereafter (p < 0.05), with the quetiapine group showing greater improvement than the lithium group. In the Montgomery Asberg Depression Rating Scale (MADRS) analysis, the difference between the quetiapine and lithium group was significant from day 28 onwards (p < 0.05), with subjects improving more in the quetiapine group than the lithium group. The treatment by week interaction showed a significant difference overall between the two groups (p < 0.0001). The severity of psychomotor retardation showed a significant decrease in the Widlocher Psychomotor Retardation Scale scores in the quetiapine (p < 0.0001) and lithium (p < 0.0001) groups. CONCLUSIONS: In this pilot study, quetiapine was an effective augmenting agent in treatment-resistant depression. PMID- 17288689 TI - Prevalence of anemia and correlation with biomarkers and specific antiretroviral regimens in 9690 human-immunodeficiency-virus-infected patients: findings of the Anemia Prevalence Study. AB - OBJECTIVE: To describe anemia prevalence and correlates with biomarkers and antiretroviral therapy (ART) in HIV/AIDS. METHODS: Multicenter, cross-sectional study; clinical laboratory data collected at single visits, including hemoglobin (Hb), CD4+ count, HIV-1 RNA. Patients receiving care at US physician offices during the year 2000. Main outcome measure was anemia (Hb < 14 g/dL [men]; < 12 g/dL [women]) and marked anemia (Hb < 11 g/dL [men]; < 10 g/dL [women]) prevalence. Multivariable models examined association of anemia prevalence with HIV-1 biomarkers and ART. RESULTS: Among 9690 patients, prevalence of anemia and marked anemia was 36% and 5%, respectively. Among 1721 patients receiving no ART, 39.7% were anemic; among 7252 receiving highly active antiretroviral therapy (HAART), 35.5% were anemic (p = 0.001). Anemia was most prevalent among men (37.3 vs. 32.3%; p = 0.0008), blacks (49 vs. 26% [whites]; p < 0.0001), patients with CD4+ < 200 cells/mm(3) (57 vs. 23% [> or = 500 CD4+]; p < 0.00001), and HIV-1 RNA > 30 000 copies/ml (53 vs. 30% [< 500 copies/ml]; p < 0.00001). Marked anemia was more common in women (6.8 vs. 4.3%; p < 0.0001). Among treated patients, logistic regression analysis controlling for CD4+, HIV-1 RNA, sex, and ethnicity, zidovudine (ZDV)-containing regimens (except combination with saquinavir/ZDV/lamivudine) were associated with increased overall anemia risk (odds ratio, 1.39 : 1.74). No regimen was associated with increased risk for marked anemia. Multivariable logistic regression showed CD4+, sex, and ethnicity more strongly associated with anemia than any ART regimen. CONCLUSION: This large, single-visit, cross-sectional, US-based study shows that anemia remains highly prevalent in HIV-infected patients. Data from this analysis suggest low CD4+ count, black ethnicity, and male sex are consistently strongest correlates of overall anemia; women are significantly more likely to have marked anemia. PMID- 17288690 TI - Erythropoietic therapy for the treatment of anemia in patients with cancer: a valuable clinical and economic option. AB - BACKGROUND: Healthcare organizations must evaluate the cost effectiveness of the alternative therapies that are available to treat anemia and improve quality of life (QoL) of patients with cancer, that is, erythropoietic protein therapy and blood transfusion. METHODS: Pharmacoeconomic studies that evaluated the cost of not treating anemia or treating with transfusion or erythropoietic protein therapy were reviewed and compared. Studies of individual erythropoietic proteins (epoetin alfa, epoetin beta or darbepoetin alfa) were also assessed. As no prospective trials have compared the erythropoietic proteins, retrospective studies and the results of separate trials were analyzed. The database searched for this review was PubMed (open date to August 2006). Recent conference abstracts were also searched (2003-July 2006). RESULTS: There is a high cost associated with anemia in cancer patients. Treatment of anemia is likely to lead to increased hemoglobin (Hb) levels and improved QoL as principal outcomes. Therefore, in assessing erythropoietic protein versus transfusion, it is more appropriate to use Hb or QoL as endpoint rather than quality adjusted life year. Studies with the former approach showed that erythropoietic protein therapy is more cost effective than transfusion. Also, its cost effectiveness should be improved with the use of evidence-based guidelines for patient selection and more tailored utilization. Increasing evidence suggests there might be differences among the erythropoietic proteins in terms of response rate, speed of response, and need for dose escalation. CONCLUSION: Significant costs are incurred when anemia in cancer is not treated. Erythropoietic protein therapy is more cost effective than blood transfusion for the treatment of cancer-related anemia. Transfusion should be reserved for patients with poor responses to erythropoietic protein or for the emergency setting, when rapid improvement in Hb is required. PMID- 17288691 TI - A psychometric comparison of three patient-based measures of asthma control. AB - OBJECTIVE: Asthma is a multidimensional disease, characterized by changes in pulmonary function, transient and chronic symptoms, and effects on quality of life. In this study, we compared the psychometric properties and screening accuracy of three patient-based asthma control instruments including: the Asthma Control Test (ACT), a brief instrument developed to assess asthma control of patients in a clinical setting; the Asthma Control Questionnaire (ACQ), an instrument developed for use in clinical research; and the 'Rules of Two', a tool that has been used in both settings. METHODS: Patients (N = 313) completed the ACT, ACQ, and Rules of Two during two asthma clinic visits 4-12 weeks apart. Office staff recorded pre- and post-bronchodilator FEV(1) measurements and asthma specialists provided a global rating of asthma control. Internal consistency reliability was computed and construct validity was evaluated using analysis of variance (ANOVA). Logistic regression and receiving operating characteristic (ROC) curve analysis was conducted to compare the screening accuracy of each measure in identifying patients with uncontrolled or moderate to severe asthma. The responsiveness of each measure to changes in asthma control and severity was tested using correlational and ANOVA methods. RESULTS: Results show that the ACT and ACQ have comparable reliability, validity, screening accuracy, and responsiveness. The Rules of Two, however, did not meet some standards and therefore has weaker psychometric properties. CONCLUSION: The ACT and ACQ are comparable asthma control questionnaires. The choice of which questionnaire to use should be informed by considering several factors, such as the intended purpose and setting where the questionnaire will be used, as well as the content, practicality, availability of benchmark scores, and adaptability to multiple administration modes of each questionnaire. One potential limitation of the study is that the data were collected in a clinical setting with limited demographic information. Hence, additional studies are needed to evaluate the psychometric properties of each instrument across demographic and clinical subgroups of the general population. PMID- 17288692 TI - A multi-centre, randomised, open-label study of atomoxetine compared with standard current therapy in UK children and adolescents with attention deficit/hyperactivity disorder (ADHD). AB - OBJECTIVE: To assess the broader efficacy (i.e., improvements in quality of life/functional outcomes) of atomoxetine compared with standard current therapy (SCT) in UK paediatric patients with ADHD and to explore clinician/parent/child perceptions of ADHD. RESEARCH DESIGN AND METHODS: A total of 201 patients with ADHD were randomised into this multi-centre, open-label study to receive atomoxetine (n = 104) or SCT (n = 97) for 10 weeks. Broader efficacy was assessed using the parent-rated Child Health and Illness Profile-Child Edition (CHIP-CE) total (global) t-score. Secondary outcome measures included the five CHIP-CE domains; parent-rated Family Burden of Illness Module (FBIM); investigator-rated ADHD-Rating Scale; investigator-rated Clinical Global Impression (CGI) Severity/Improvement scales; and child-rated Harter Self-Perception Profile (HSPP). RESULTS: Quality of life of children/adolescents with ADHD was extremely compromised at baseline (CHIP-CE total t-scores: atomoxetine, 23.2 +/- 12.2; SCT, 23.9 +/- 11.0), and improved during the 10-week study for both groups; the CHIP CE score was statistically significantly higher for patients treated with atomoxetine (38.4 +/- 1.3) compared with SCT (30.8 +/- 1.3) at week 10 (p < 0.001). ADHD-RS, CGI-Severity, and CGI-Improvement scores were significantly different between the groups in favour of atomoxetine (p < 0.001). There was a statistically significant difference between the groups in the HSPP Social Acceptance domain in favour of atomoxetine, but not in the five other HSPP domains or FBIM total score. Atomoxetine was well-tolerated. CONCLUSIONS: Results from this open-label trial show that atomoxetine is superior to SCT in addressing broader efficacy and functional outcomes in UK children/adolescents with ADHD. This study contributes to the understanding of broader efficacy in children with ADHD, and is timely in light of recent NICE guidance. PMID- 17288693 TI - Long-term trial of bosentan monotherapy for pulmonary arterial hypertension in Japanese patients. AB - OBJECTIVE: To determine the efficacy and safety of long-term bosentan monotherapy in Japanese patients with pulmonary arterial hypertension (PAH). RESEARCH DESIGN AND METHODS: The present study was an extension to a 12-week open-label trial of bosentan in which 21 Japanese patients with PAH received bosentan, 125 mg twice daily. Of the 21 patients in the initial trial, 20 elected to participate in the long-term study and to continue to receive bosentan for up to 3 years. MAIN OUTCOME MEASURES: The primary efficacy measure was comparison of World Health Organization (WHO) functional class for pulmonary arterial hypertension following long-term (> 2.5 years) therapy compared with baseline (prior to initiation of bosentan). Secondary outcomes included time from initiation of bosentan therapy to clinical worsening and safety assessments. RESULTS: Bosentan treatment was continued for a median of 2.7 years (range 0.4-3.0 years); 12 patients received bosentan monotherapy for at least 2.5 years. Following long-term treatment, improvement of WHO functional class compared with baseline was observed in 9/12 patients (75.0%) and in 3/12 patients (25.0%) the functional class remained stable; no patient experienced a worsening of WHO functional class compared with baseline. Overall, long-term treatment with bosentan was well tolerated. CONCLUSIONS: Long-term treatment with bosentan is well tolerated and is associated with sustained clinical improvement in Japanese patients with PAH. Bosentan, therefore, represents a valuable treatment option for Japanese patients with this devastating disease. PMID- 17288694 TI - Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. AB - OBJECTIVE: The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment. The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine (a dual serotonin and norepinephrine reuptake inhibitor) and escitalopram (a selective serotonin reuptake inhibitor). RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, placebo- and active comparator controlled study, in which patients (> or = 18 years) meeting DSM-IV criteria for Major Depressive Disorder (MDD) received duloxetine 60 mg once daily (QD; N = 273), escitalopram 10 mg QD (N = 274), or placebo (N = 137) for 8 weeks. The primary objective was to compare the onset of antidepressant efficacy, by testing the hypothesis that the percentage of duloxetine-treated patients achieving onset criteria at Week 2 was not inferior to that in the escitalopram group. MAIN OUTCOME MEASURES: Onset of efficacy was defined as a 20% decrease from baseline on the 17-item Hamilton Rating Scale for Depression (HAMD(17)) Maier subscale that was maintained or exceeded at all subsequent visits. RESULTS: Probabilities of meeting onset criteria at Week 2 for duloxetine- and escitalopram-treated patients were 42.6% versus 35.2%, respectively (treatment difference = 7.4%; 95% confidence interval, -1.3% to 16.2%; p = 0.097). Both drugs showed significant improvement compared with placebo (p < or = 0.05) on the primary efficacy measure (Maier subscale) at Week 1 and endpoint (Week 8). No differences were found between duloxetine, escitalopram, and placebo rates of remission or response at 8 weeks. Adverse events that occurred significantly more frequently among duloxetine-treated patients when compared with those receiving escitalopram were nausea, dry mouth, vomiting, yawning, and irritability. The rate of discontinuation due to adverse events did not differ significantly between treatment groups. LIMITATIONS: Given the difficulties in constructing appropriate dose comparisons, the results of this study should be interpreted specific to the doses tested and not extrapolated to the drug as a whole. This study employed a fixed-dose design; flexible-dose designs are more likely to find a difference between antidepressants and placebo. CONCLUSION: In this study, both duloxetine and escitalopram showed significantly greater improvement on the primary efficacy measure than placebo over the 8-week acute treatment period, while no differences were observed between drugs or between drugs and placebo on response and remission rates at 8 weeks. Escitalopram at a starting dose of 10 mg QD was better tolerated than duloxetine at a starting dose of 60 mg QD. This study met its pre-defined primary objective of assessing if duloxetine was non-inferior to escitalopram in antidepressant onset efficacy, and the results show that duloxetine is at least as fast as (non-inferior to) escitalopram. PMID- 17288695 TI - Comparison of health care costs and co-morbidities between men diagnosed with benign prostatic hyperplasia and cardiovascular disease (CVD) and men with CVD alone in a US commercial population. AB - OBJECTIVE: The purpose of this study was to compare costs and treatment patterns between men with concomitant benign prostatic hyperplasia (BPH) and CVD to men with CVD (but not BPH). STUDY DESIGN: A retrospective, matched cohort study was utilized to assess costs and treatment between two study populations. METHODS: The data source was administrative claims from managed care organizations between January 1, 1997 and December 31, 2004. A control group of men with CVD only was created matching by age, index CVD diagnosis date, and CVD diagnoses. Diagnosis and procedure codes identified men with BPH and CVD. Differences in medical costs, co-morbidities, and drug treatments were assessed. RESULTS: Approximately 39% of men identified with BPH also had some form of CVD at the time of BPH diagnosis. Men with BPH and CVD were more likely to have additional co morbidities, more frequently received medications for CVD and non-CVD disorders, had 44% higher total medical costs than men with CVD only (p < 0.001), and had 42% higher CVD-related costs (p < 0.001) than men with CVD only. LIMITATIONS: The population studied in this analysis was primarily working individuals with health benefits provided by managed care plans; therefore, the results may not generalize to other populations. CONCLUSIONS: This study demonstrates in a commercial payer population that men with concomitant BPH and CVD have more co morbidities, receive pharmacologic agents more frequently, and have higher health care resource utilization than men with CVD only. Due to the high prevalence of co-morbid BPH and CVD, screening for BPH in men presenting with CVD may assist with earlier disease identification and cost management over time. PMID- 17288696 TI - Resource utilization in asthma: combined fluticasone propionate/salmeterol compared with inhaled corticosteroids. AB - BACKGROUND: Asthma management guidelines recommend low-dose inhaled corticosteroids (ICS) for initial treatment of mild persistent asthma. Instead, data from primary care practice show that many patients start on combination therapy with fluticasone propionate/salmeterol (FPS) for mild asthma. The consequences of this variance from guideline recommendations are not well described. OBJECTIVE: Compare healthcare utilization and asthma-related outcomes for patients with mild asthma who began treatment with FPS or ICS alone. Design and data source: A retrospective analysis of asthma-related insurance claims. Patients initially treated with FPS or ICS were identified from an administrative health insurance claims database and followed for 1 year. Analyses of resource utilization 6 months before therapy initiation identified patients with mild asthma. Propensity score matching managed between-group differences in clinical characteristics and controlled for selection bias. OUTCOME MEASURES: Resource use was determined for asthma-related outpatient visits, emergency room services, hospitalizations, and medications. RESULTS: Demographic characteristics and comorbidities were similar for each group (FPS, n = 1888; ICS, n = 1888). During the 12-month follow-up period, total asthma-related costs were significantly higher for FPS versus ICS (1206 vs. 804 dollars; p < 0.0001), owing primarily to significantly higher drug costs for FPS versus ICS (677 vs. 357 dollars; p < 0.0001). The percentage of patients experiencing an exacerbation (14.0% FPS, 13.5% ICS) and the average number of exacerbations in each group (0.175 FPS, 0.164 ICS) were similar. CONCLUSIONS: Healthcare costs were found to be lower in patients receiving ICS than in those receiving FPS, with similar health outcomes in both groups. Study limitations included the use of claims data and a proxy definition of asthma severity, and potential confounding by unobserved factors. PMID- 17288697 TI - Effect of inhaled insulin on patient-reported outcomes and treatment preference in patients with type 1 diabetes. AB - OBJECTIVE: To compare patient-reported outcomes and treatment preference between preprandial inhaled insulin and preprandial subcutaneous (SC) insulin in the context of a clinical trial of crossover design with a primary objective of comparing HbA(1C) between groups. RESEARCH DESIGN AND METHODS: Multi-center, randomized, open-label, two-arm crossover trial conducted in the US and Canada with two 12-week periods comparing preference between preprandial human insulin inhalation powder (HIIP; AIR inhaled insulin) and preprandial SC insulin (regular human insulin or insulin lispro) in patients with type 1 diabetes. Patients received HIIP plus insulin glargine during period 1 and SC insulin plus insulin glargine during period 2, or the reverse sequence. MAIN OUTCOME MEASURES: SF-36 Vitality Subscale, Diabetes Symptom Checklist-Revised subscales, Diabetes Treatment Satisfaction Questionnaire, Insulin Delivery System Questionnaire, HIIP specific questionnaire, preference question. RESULTS: Of 137 patients entered, 119 completed the study (54% female, mean age 40.9 +/- 12.4 years, mean HbA(1C) 8.1 +/- 1.0%). Patients had significantly greater treatment satisfaction and more positive evaluation of their insulin delivery system (easier to control blood sugar, less lifestyle impact) with HIIP than with SC insulin (all p < 0.01). Patients preferring HIIP (80%) were significantly more confident about (p = 0.005) and comfortable with (p = 0.003) using the system than those preferring SC insulin. Results may not be generalizable to all patients with type 1 diabetes. CONCLUSIONS: Some patients desire alternatives to insulin injection. In this study 80% preferred HIIP to injected insulin. Other patients feel more comfortable with familiar insulin delivery. Healthcare providers should help patients find insulin delivery that corresponds to individual preferences. PMID- 17288698 TI - Potential mechanisms of stroke benefit favoring losartan in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. AB - INTRODUCTION: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study is the first, and, so far, the only endpoint trial in patients with hypertension and left ventricular hypertrophy (LVH) to show a divergent therapeutic outcome of one treatment modality over another with equivalent blood pressure control. The purpose of this article is to review post hoc sub-analyses of LIFE study data and other clinical studies that offer some insight into possible treatment-related differences contributing to the superior stroke outcome of losartan versus atenolol beyond blood pressure reduction. METHODS: Relevant randomized clinical trials and review articles were identified through a MEDLINE search of English-language articles published between 1990 and 2006 using the search terms losartan, atenolol, LIFE, hypertension, and LVH. Articles describing major clinical studies, new data, or mechanisms pertinent to the LIFE study were selected for review. RESULTS: Differences in blood pressure or in the distribution of add-on medications were not evident between study groups in the LIFE study. Thus, the observed outcomes benefits favoring losartan may involve other possible mechanisms, including differential effects of losartan and atenolol on LVH regression, left atrial diameter, atrial fibrillation, brain natriuretic peptide, vascular structure, thrombus formation/platelet aggregation, serum uric acid, albuminuria, new-onset diabetes, and lipid metabolism. Alternative explanations for the LIFE study findings have also been put forward, including the choice of atenolol as an appropriate active comparator and differential effects between treatment groups on central pulse pressure. Additional clinical trials are needed to determine if the beneficial effects of losartan seen in LIFE are shared by other inhibitors of the renin-angiotensin system. CONCLUSION: Sub-analyses of the LIFE study data suggest that losartan's stroke benefit may arise from a mosaic of mechanisms rather than a single action. Further studies are expected to continue to delineate the mechanisms of differential responses to treatments in LIFE. PMID- 17288699 TI - Role for 5-day, once-daily extended-release clarithromycin in acute bacterial exacerbation of chronic bronchitis. AB - BACKGROUND: Clarithromycin is commonly dosed for 7 or more days in patients with acute bacterial exacerbation of chronic bronchitis (ABECB). Studies with other antibiotics have shown equivalent efficacy, reduced/similar frequency of adverse events, improved adherence and patient satisfaction, and lower treatment costs with a shorter treatment course. PATIENTS AND METHODS: The study population was derived from two multicenter, randomized, double-blind (North America)/single blind (France) comparative trials in which outpatients at least 35 years old with a presumptive diagnosis of obstructive ABECB were randomized to receive clarithromycin extended-release (ER) 1000 mg once daily for 5 days or a comparator agent--clarithromycin immediate-release (IR) 500 mg twice daily for 7 days (in North America) or telithromycin 800 mg once daily for 5 days (in France). RESULTS: A total of 818 patients were randomized (411 to clarithromycin ER and 407 to a comparator agent). The clinical cure rate in clinically evaluable patients at the follow-up visit was 90% each for the clarithromycin ER group (318/353) and the comparator group (318/355). The patient bacteriological cure rate and the overall target pathogen eradication rate in clinically and bacteriologically evaluable patients were each 92% for the clarithromycin ER group (155/168 and 189/205, respectively) and 93% for the comparator group (147/158 and 183/197, respectively) at the follow-up visit. The study drugs were generally well tolerated, with < 2% of patients discontinuing their treatment prematurely due to a drug-related adverse event. The incidence of drug-related adverse events was 18% (73/411) in the clarithromycin ER group and 24% (97/407) in the comparator group. Clarithromycin ER-treated patients reported statistically significantly fewer episodes of abdominal pain than did patients treated with a comparator agent (0.2% vs. 1.7%, respectively; p = 0.037). This combined analysis is limited by differing blinding methods, comparator agents, and their duration of administration. Furthermore, many patients were excluded from the clinically and bacteriologically evaluable group due to lack of a pretreatment target pathogen. CONCLUSION: A once daily, 5-day clarithromycin ER regimen appears to be a suitable choice for treating patients with ABECB. PMID- 17288700 TI - Breaking the first law of informatics: the Quality and Outcomes Framework (QOF) in the dock. PMID- 17288701 TI - Prometheus: the implementation of clinical coding schemes in French routine general practice. AB - BACKGROUND: Clinical data are most useful, both at the individual level and collectively, if they are coded according to a standard classification system. However, clinicians often have little motivation to routinely code their consultation data. The main classification systems available in French primary care are the International Classification of Primary Care (ICPC) and the Dictionary of Consultation Results (DCR). OBJECTIVE: To assess the feasibility of using the ICPC-2 and the DCR for coding health problems managed in routine general practice in France. METHODS: Between December 2001 and June 2003, 61 volunteer general practitioners (GPs) from the Paris area prospectively recorded the health problems they managed at consultations, using either the ICPC (36 GPs) or the DCR (25 GPs), for a period of six months. They were equipped with one of three proprietary medical software applications specifically adapted for the study, or one open source utility, interfacing with five other, non-adapted, proprietary software programs. They had a two-day training session, were financially compensated, and were provided with electronic feedback. RESULTS: The mean reported coding time per consultation was 2.5 minutes, but 28 physicians (46%) judged the coding time excessive and reported a maximum acceptable time of 1.2 minutes. Coding consultation data was considered more useful at the collective level (by 95% of physicians) than at the individual practice level (by 69%). Only 34 physicians (56%) expressed willingness to carry on routine coding after the end of the study. Some results differed depending on the classification system used, especially due to confounding factors, as some physicians could have previously used the given system. CONCLUSIONS: Coding health problems on a routine basis proved to be feasible. However, this process can be used on a more widespread basis and linked to other management data only if physicians are specially trained and rewarded, and the software incorporates large terminologies mapped with classifications. PMID- 17288702 TI - Primary care oncology: addressing the challenges. AB - The last decade has seen an emerging clinical discipline known as 'primary care oncology' that describes the involvement of general practitioners (GPs) in preventing, diagnosing, treating and following up patients with cancer. This paper reports the experience of our team in investigating the information required to develop a shared electronic care record system to link GPs and cancer specialists in Wales in order to facilitate information sharing between them in a timely and effective manner. It identifies a potential minimum dataset that can provide the basis for the development of a Welsh primary care cancer dataset. It also addresses the associated challenges to be overcome at implementation, namely information, technical, cultural/organisational and management challenges. This work is a collaboration between the Department of Computer Science at Cardiff University and Velindre NHS Trust, the South East Wales Cancer Centre. PMID- 17288703 TI - Integrating data for learning disabilities service providers: are the barriers and solutions technical or organisational? AB - Since the publication of the Government White Paper 'Valuing People: a new strategy for learning disability for the 21st century', the responsibility for providing health care for people with learning disabilities has shifted rapidly to primary care. However, people with learning disabilities are supported by a disparate group of providers, from health care through local authorities to the voluntary sector, with resultant difficulties in providing seamless care. There would seem to be considerable potential for 'joined-up' data and information services to improve this situation, and Semantic Web technologies offer many enticing possibilities in this regard. However, to be effective, many organisational and policy issues have to be addressed; not least among these is the concern of patient confidentiality. This is particularly pertinent given that people with learning disabilities might be less able to make informed decisions. The approach that this paper takes is to review the policy and service scenarios that would benefit from 'joined-up' data, and then, based on user feedback from a series of seminars with stake-holders on these issues, explore what works well, what works less well, and to offer suggestions for future developments. PMID- 17288704 TI - The development and evaluation of alternative communication strategies to facilitate interactions with Somali refugees in primary care: a preliminary study. AB - The work reported in this paper forms part of a larger project to develop and evaluate alternative forms of communication to facilitate cross-cultural consultations in primary care. As a case study and proof-of-concept, work was conducted with Somali refugees who tend to experience significant communication difficulties in primary care consultations. The alternative communication methods developed in this study originate from the field of Augmentative and Alternative Communication (AAC). These methods may include non-verbal communication or aided communication using a mix of pictographic symbols, bilingual text and digitised (recorded) or synthetic speech. These can be delivered on a range of paper-based or computer-based devices. A paper-based and computer-based method was developed to assess whether a group of literate and illiterate Somalis were able to answer a set of questions using these tools. The purpose of this preliminary study was to assess whether either of these communication methods were suitable for further evaluation in primary care consultations. Twenty Somalis were presented with three communication tools and were asked a set of general questions in Somali which they had to answer using each tool: (1) a paper-based communication book containing symbols and bilingual text labels; (2) a laptop PC with mouse pad containing the same symbols, text labels and augmented with digitised Somali speech; (3) a tablet PC with touch screen containing the same software and digitised Somali speech. These two computer-based delivery platforms were compared for ease of use among a participant group who are likely to have little computing experience. Each task was timed and scored for level of correctness; feedback was gained from Somalis and experimenters' observations were noted. Participants clearly found the computerised devices with Somali speech output easier to use and more acceptable than the simpler paper-based device. PMID- 17288705 TI - Liverpool Telecare Pilot: telecare as an information tool. AB - The role of telecare systems is normally seen as identifying, and drawing attention to, situations of concern in the homes of service users. While this may currently be the primary reason for deploying such systems, the scope of telecare should not be limited to such an alarm generation role. The role of telecare in enhancing community-based care provision may be broadened by using similar, or identical, technology for providing relevant information to the carers of service users. In this paper we present a technical overview and discussion of an information provision approach to telecare which was trialled as one aspect of a pilot service in Liverpool, UK. The service used data collected by the telecare system to produce visual daily behavioural profiles and presented these to carers. The recipients for these profiles included social workers, occupational therapists and relatives of the service users. In this paper we discuss the visual profiles together with the benefits offered by such an information provision approach, including the perspective of a occupational therapist based in Liverpool. PMID- 17288706 TI - Liverpool Telecare Pilot: case studies. AB - Telecare services use information and communications technology (ICT) to support the provision of care to people in their own homes. This paper describes a pilot telecare service employed by Liverpool (UK) City Council to support a sample of their frail and elderly social services users. The pilot has been running for over two years and has been deployed for 21 individuals in Liverpool. In this paper we present the pilot system and provide real example cases which help to illustrate the benefits of such a system. PMID- 17288707 TI - Routinely collected general practice data: goldmines for research? A report of the European Federation for Medical Informatics Primary Care Informatics Working Group (EFMI PCIWG) from MIE2006, Maastricht, The Netherlands. AB - BACKGROUND: Much of European primary care is computerised and many groups of practices pool data for research. Technology is making pooled general practice data widely available beyond the domain within which it is collected. OBJECTIVE: To explore the barriers and opportunities to exploiting routinely collected general practice data for research. METHOD: Workshop, led by primary care and informatics academics experienced at working with clinical data from large databases, involving 23 delegates from eight countries. Email comments about the write-up from participants. OUTPUTS: The components of an effective process are: the input of those who have a detailed understanding of the context in which the data were recorded; an assessment of the validity of these data and any denominator used; creation of anonymised unique identifiers for each patient which can be decoded within the contributing practices; data must be traceable back to the patient record from which it was extracted; archiving of the queries, the look-up tables of any coding systems used and the ethical constraints which govern the use of the data. CONCLUSIONS: Explicit statements are needed to explain the source, context of recording, validity check and processing method of any routinely collected data used in research. Data lacking detailed methodological descriptors should not be published. PMID- 17288714 TI - It's teamwork...but it isn't easy. PMID- 17288716 TI - Localised periodontitis associated with an ectopic orthodontic separator. AB - A case of localised periodontitis associated with a subgingival orthodontic separator is presented. The presence of this object was related to quite severe periodontal breakdown around an upper right first premolar tooth in an otherwise unsusceptible individual. PMID- 17288717 TI - Do dental anxiety questionnaires raise anxiety in dentally anxious adult patients? A two-wave panel study. AB - OBJECTIVE: To test whether or not dentally anxious patients attending the dentist for an appointment become more anxious when completing a dental anxiety questionnaire. BASIC RESEARCH DESIGN: Patients were initially screened to include only those who were dentally anxious. A pre- and post-test was planned with the completion of the Modified Dental Anxiety Scale (MDAS) questionnaire as the intervention. CLINICAL SETTING: Two dental access centres in the North West of England. PARTICIPANTS: Initially, 583 patients were screened. Of these, 182 (31%) were found to be dentally anxious and were recruited into the study. MAIN OUTCOME MEASURES: State-Trait Anxiety Inventory Scale Short Form. RESULTS: State anxiety did not change with the completion of the MDAS questionnaire in either designated dental phobics (MDAS >or=19) or those classified as non-phobics (MDAS <19). CONCLUSIONS: The MDAS can be used to assess dental anxiety without raising anxiety in patients with or without self-reported dental phobia. PMID- 17288719 TI - Perceptions and attitudes to a fundamental reform of general dental services in Wales. AB - BACKGROUND: The greatest reform of state-funded dental care in England and Wales, since the inception of the National Health Service (NHS) in 1948, occurred on 1st April 2006. It encompassed the dissolution of a universal national contract and the introduction of locally commissioned primary dental care services in England and Wales. Suggested advantages included the elimination of the fee-for-item-of service 'treadmill', an increased emphasis on prevention, and improved access-at a time when many practitioners were opting to provide care outside the NHS system. OBJECTIVES: This study investigated the perceptions and attitudes to the new contract, in the three months immediately prior to its implementation. METHODOLOGY: Data were collected via a postal questionnaire, comprising a combination of 56 closed and open questions. The questionnaire was mailed to all general dental practitioners in Wales. RESULTS: 691 (64.5%) questionnaires were returned. Just 140 (23%) dentists agreed or strongly agreed that they would have more time to spend with patients under the new contract. The majority of respondents, 361 (59.3%), disagreed that they would be able to spend more time on prevention. Three hundred and sixty-six (60.2%) disagreed that they were strongly attracted by the new method of remuneration and only 62 (10.2%) perceived a reduced level of administration. Of the 608 dentists who provided NHS dental services, 418 (68.6%) indicated they would continue to do so, 130 (21.4) were undecided, and 55 (9%) stated that they would not take up the new contract. Allowing for the number of days worked per week and the percentage time spent on NHS patients, these equate to 72.3%, 21% and 5.9% of NHS capacity respectively. CONCLUSIONS: This study has established baseline perceptions of reform in state funded dental care in Wales. As the new contract evolves, it will be interesting to determine whether the largely negative perceptions of new ways of working expressed in this study are realised. PMID- 17288722 TI - Opportunities for prevention: more than 'just the mouth'. AB - This paper has been written by two dentists from Colombia who are currently waiting to take the International Qualifying Examination. They have been working as dental nurses in London and have gained insights into both NHS and non-NHS practice in London. They have a particular interest in preventive dentistry and have analysed recent developments in England with regard to the prevention of disease and oral disease in primary care. They propose a preventive approach which brings together recent policy developments in the United Kingdom and worldwide. They conclude that there are now potentially better opportunities than ever before to develop programmes to promote health and prevent oral disease, and to adopt a team approach to achieve these goals. PMID- 17288729 TI - Pharmaceutical prescribing for children. Part 6. The management of medical emergencies in children in dental practice. AB - This paper is the seventh in the series on prescribing medicines for child dental patients. Here, the authors aim to describe the medical emergencies that may occur in children presenting for dental treatment and to provide guidelines on their management, with particular reference to the use of emergency drugs. PMID- 17288731 TI - Osteonecrosis of the jaw after treatment with bisphosphonates is irreversible, so the focus must be on prevention. PMID- 17288732 TI - Reduced mRNA and protein expression of BCL-2 versus decreased mRNA and increased protein expression of BAX in breast cancer brain metastases: a real-time PCR and immunohistochemical evaluation. AB - OBJECTIVES: Brain metastases are an increasingly common complication in breast cancer patients. Apoptosis regulating genes are promising candidates for further treatment options. We examined the mRNA and protein expression of p53, BCL-2 and BAX in breast cancer brain metastases versus primary tumors. METHODS: In a two step approach p53, BCL-2 and BAX mRNA expression in ductal invasive breast cancer brain metastases was examined by: (1) reverse transcription-polymerase chain reaction (RT-PCR) mRNA expression screening (band appearance in relation to an internal standard) and (2) quantitative real-time RT-PCR (CT-values in relation to an internal standard). Protein expression using immunohistochemistry. Results were compared with primary tumors. RESULTS: We found significantly lower BCL-2 mRNA and protein expression in breast cancer brain metastases versus primary tumors. P53 mRNA and protein expression was also lower in metastases. However, this difference was only significant on mRNA but not on the protein level. BAX expression evaluation revealed was contradictory results: mRNA expression was significantly lower whereas protein expression was significantly higher in metastatic lesions. DISCUSSION: The mRNA and protein expression of p53 and BCL-2 seems to be reduced in breast cancer brain metastases. BAX mRNA and protein may be regulated differentially in metastatic lesions. PMID- 17288733 TI - Role of extracellular matrix components in facial nerve regeneration: an experimental study. AB - OBJECTIVE: The aim of this study is to evaluate the role of extracellular matrix components in nerve regeneration. Matrigel, a complex of extracellular matrix components such as laminin (the most abundant) heparan sulphate proteoglycans (HSPG), type IV collagen and fibronectin, was used. METHODS: Forty male rabbits, which had undergone section of the right facial nerve, were later treated by reinnervation through an artificial graft of expanded polytetrafluoroethylene (ePTFE). In 20 animals the tubes of ePTFE were filled with Matrigel; in 20 control animals the tubes were filled with saline solution. RESULTS: The Matrigel group showed a better axonal organization and a significantly higher number of regenerated axons in the early phases (at days 15 and 30 respectively) than the control group, whereas the difference of the axons number at day 60 was less significant; besides, the axon diameter and the myelin thickness were not significantly improved by Matrigel. DISCUSSION: Our data suggest that Matrigel is an important factor in promoting and enhancing the early phases of the regeneration after nerve injuries. Tree neurite promoting agents, such as laminin, fibronectin and collagen, allow a more systematic and agonized regeneration. Extracellular matrix components may represent a direction guidance for axonal pathway. PMID- 17288734 TI - The role of spinal tissue scarring in the pathogenesis of progressive post traumatic myelomalacia. AB - OBJECTIVES: Experimental spinal cord injury (SCI) with focal spinal tissue scarring was studied to better understand the progressive post-traumatic myelomalacia (PPM). METHODS: Using a stereotactic device, the authors developed an acute compression of spinal cord at Th-10 in the adult rat. In Group A, the rat thoracic spinal cord was compressed epidurally with preservation of local cerebrospinal fluid (CSF) dynamics. In Group B (spinal tissue scarring), the rat thoracic spinal cord was compressed directly after disruption of meninges of dura mater and arachnoid membrane, followed by gelatine sponge sealing. All rats were maintained for 12 weeks after injury. RESULTS: Imaging analysis revealed the significant increase of cystic cavitation in the contused spinal cord in Group B compared with Group A. Anterograde axonal tracing demonstrated that the labeled corticospinal axons had extended axonal sprouting into the nearby gray matter and displayed prominent dieback at the rostral interface of the spinal cord lesion in both groups. No significant difference in motor and sensory functions between the two groups was noted. DISCUSSION: The new experimental model of PPM formation was devised. Spinal tissue scarring at the injury site may cause a tethering effect on the spinal cord, which may lead to significant alteration of the spinal cord parenchyma. Although the devastating effect of PPM on motor and sensory functions is still not resolved completely, the results in the present study suggest the importance of careful analysis in the treatment of PPM after SCI. PMID- 17288735 TI - Coagulation factor XIII Val34Leu gene polymorphism and Alzheimer's disease. AB - Blood coagulation factor XIII (FXIII) plays a role in inflammatory processes and a pathogenetic role of inflammation in neurodegenerative disorders has been proposed. FXIIIa subunit was immunohistochemically detected in a subpopulation of reactive microglia in Alzheimer's disease (AD). Aim of the present study is to evaluate whether a common polymorphism of the FXIII gene is associated with sporadic AD. We examined 90 patients affected by sporadic AD and 139 age- and sex matched controls to assess the distribution of V/L alleles and genotypes of the FXIIIa-subunit gene. The LL genotype showed a significantly higher frequency in AD patients (p<0.05) with a significantly increased risk of AD in the presence of LL genotype at the logistic regression analysis [odds ratio: 3.6 (1.36-9.44), p<0.01]. This study shows for the first time an association between FXIII Val34Leu polymorphism and AD. PMID- 17288736 TI - The role of cerebral cyst formation in the intractability of epilepsy. AB - OBJECTIVES: The aims of the present study were: (1) to examine single focal, intractable epilepsy associated with gliotic changes and (2) to discuss the mechanisms underlying seizure intractability. PATIENTS AND METHODS: Records of 34 patients with surgically treated intractable epilepsy were analysed retrospectively. Thirteen out of 34 patients had single epileptic focus histologically identified as a gliotic change. Seizure types, neuroradiological findings including the location and size of the foci, the hemosiderin deposition and calcification, intra-operative findings, and pathological findings of 13 patients were analysed in this study. Whether cyst formation was presented was also recorded. Tailored resections of epileptogenic lesions were performed using electrocorticography and ultrasonography. RESULTS: Cyst formations were observed in 10 out of 13 patients. In eight of the patients with cyst formation, seizures initially were well controlled, but the subsequent seizures increased in both severity and frequency in a stepwise manner. All patients with cyst formation became seizure free after the removal of the cyst wall and surrounding gliotic tissue. CONCLUSIONS: Analyses of the clinical courses, pathological and hydrodynamic findings suggest that the gliotic changes secondarily induced by cystic changes in brain parenchyma appear to play an important role in seizure intractability. We adapted the 'Starling resistor model' of hydrodynamics as a hypothetical model for the intracranial cyst and fluid passage to explain the mechanisms of the formation of epileptogenic gliotic changes. PMID- 17288737 TI - Characterization of the eIF2-associated protein p67 during brain ischemia and reperfusion. AB - OBJECTIVES: Within the first few minutes of reperfusion after global brain ischemia, there is a severe depression of protein translation owing to phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2). There is a 67 kDa peptide (p67) that, in its glycosylated form, binds to eIF2 and protects eIF2alpha from phosphorylation. Moreover, cells with high p67 content exhibit enhanced resistance to eIF2alpha phosphorylation. To examine the possibilities that deglycosylation of brain p67 occurs during ischemia and/or early reperfusion or that p67 deglycosylation may be more extensive in the vulnerable neurons, these experiments were undertaken to characterize the localization and activation state of p67 during early brain reperfusion METHODS: Western blots using antibodies that recognize total p67, glycosylated p67 and phosphorylated eIF2alpha were used to characterize total p67 and glycosylated p67 during reperfusion-induced phosphorylation of eIF2alpha. We also characterized the immunohistochemical distribution of glycosylated p67 before and after brain ischemia and reperfusion. RESULTS: There was a large increase in phosphorylated eIF2alpha, but there was no decrease in the levels of total or glycosylated p67 from those observed in controls following 10 minutes complete brain ischemia and 10 or 60 minutes subsequent reperfusion. Furthermore, there was no reduction in localized immunostaining for glycosylated p67 in vulnerable neurons during ischemia and reperfusion. DISCUSSION: It does not appear that p67 plays a significant role in regulating the phosphorylation of eIF2alpha following transient brain ischemia. PMID- 17288738 TI - Different expression of low density lipoprotein receptor and ApoE between young adult and old rat brains after ischemia. AB - OBJECTIVES: Reduction of brain plasticity underlies the poor outcome of aged stroke patients. The molecular mechanism of plasticity reduction by aging is uncertain, but disturbed lipid metabolism may be implicated. METHODS: We investigated the expression of low density lipoprotein receptors (LDL-R) and apolipoprotein E (ApoE), both of which play active roles in lipid metabolism in young adult and old rat brains after ischemia. RESULTS: LDL-R, trivially expressed in the sham-operated brain neurons, was increased from day 1 and became prominent at days 7 and 21 at the peri-ischemic cortex. The magnitude was smaller in the old than in the young adult rats. ApoE was increased in the astrocytes and neurons of the peri-ischemic cortex at day 1, which became further pronounced in the neurons but not in the astrocytes at days 7 and 21. ApoE expression was again less prominent in the old animals at days 7 and 21. DISCUSSION: As ApoE containing lipoprotein is recruited via LDL-R, the present results suggest that old brains had less capability to induce LDL-R, which resulted in impaired recruitment of lipoprotein after the ischemic injury. Impaired lipid recruitment causes disturbance of synaptogenesis and thus brain plasticity reduction. This molecular mechanism may result in poor functional recovery of aged stroke patients. PMID- 17288739 TI - Acute neurovascular unit protection by simvastatin in transient cerebral ischemia. AB - Acute vascular- and neuroprotective effects of simvastatin were evaluated in a rat model of transient, focal cerebral ischemia. Male, Wistar rats (n=12) underwent transient middle cerebral artery (MCA) occlusion for 3 hours followed by 3 hours of reperfusion. After 30 minutes of MCA occlusion, four rats each were subcutaneously injected with either 20 or 40 mg/kg of simvastatin. At the end of 3 hours of reperfusion, tissue injury and blood-brain barrier (BBB) opening were quantified by histology and [(14)C]-alpha-aminoisobutyric acid (AIB)-based quantitative autoradiography (QAR), respectively. Compared with untreated rats, those treated with simvastatin (20 mg/kg) had reduced volumes of AIB leakage, tissue pallor and distribution space for AIB (p<0.05). No additional effects were seen with the higher drug dose (40 mg/kg). These data suggest that the acute neuroprotective effects of statins are in part owing to attenuation of stroke induced changes in BBB permeability. PMID- 17288740 TI - The effect of normothermic and hypothermic hypoxia-ischemia on brain hypoxanthine phosphoribosyl transferase activity. AB - OBJECTIVES: Cerebral hypoxia-ischemia leads to the depletion of ATP. Hypoxanthine, a degradation product of ATP, can be salvaged by hypoxanthine phosphoribosyl transferase (HPRT) and used to reform high-energy purines. Hypothermia conserves ATP in hypoxia-ischemia, possibly by preserving HPRT activity. We hypothesized that cerebral hypoxia-ischemia would decrease the activity of this enzyme, and that this reduction would be attenuated by moderate hypothermia. METHODS: Three groups of rabbits were evaluated. Normothermic rabbits were exposed to 8 minutes of hypoxia, 8 minutes of cerebral ischemia, and 30 minutes or 4 hours of cerebral reperfusion. Hypothermic rabbits were cooled to a brain temperature of 33-34 degrees C throughout identical injury and reperfusion periods. Control rabbits underwent the same preparation, without hypothermia or injury. HPRT activity in the cortex, hippocampus, thalamus, caudate, and cerebellum was measured spectrophotometrically. RESULTS: There were no significant differences (p>0.05) in enzymatic activity when comparing the three groups of animals, regardless of reperfusion time or brain temperature. Within the control group, some regional differences in enzyme activity were noted. DISCUSSION: The results indicate that brain HPRT activity is unaffected by hypoxia-ischemia, even after 4 hours of reperfusion and regardless of brain temperature. This study supports the importance of this enzyme in the conservation of brain purines after neurologic injury. PMID- 17288741 TI - Effects of laserneedle stimulation in the external auditory meatus on brainstem and very early auditory evoked potentials in humans. AB - OBJECTIVES: For the first time, brainstem auditory evoked potentials (BAEP) and very early auditory evoked potentials (EAEP) were investigated in 23 volunteers (mean age: 26.5 +/- 3.6 years) under resting conditions and during continuous and frequency modulated (2 Hz) laser stimulation in the external auditory meatus. METHODS: Using a new ear adapter, the outer region of the auditory canal was stimulated with laser light (685 nm, 4 x 30-40 mW, duration: 10 minutes). RESULTS: The EAEPs were significantly changed during continuous (p=0.019), as well as frequency modulated (p=0.014) laser stimulation compared with control measurements. DISCUSSION: Physiologic alterations of inner ear mechanism such as extra-cerebral changes in conductance or stimulation-dependent depolarization processes in extra-cerebral regions of the auditory system could be possible explanations for the significant difference in measurement parameters. PMID- 17288742 TI - The histopathological and electron-microscopic examination of the stereotactic pulsed radiofrequency and conventional radiofrequency thermocoagulation lesions in rat brain. AB - OBJECTIVE: Neurodestructive procedures have been used for treating intractable pain for a long time. Pulsed radiofrequency (RF) is a newly defined energy type. Pulsed RF may be used in the treatment of patients with some pain syndromes in whom the pain could not be controlled by the alternative techniques. The objective of the present study was to examine the histological and electron microscopical changes in rat brain after pulsed RF application. METHODS: Forty five male rats were used in these experiments. Lesions were applied stereotactically to the target areas of the rat brains. Two different RF energy type were used as representative models of pulsed-RF and conventional-RF procedures. The rats were kept alive for 21 days and then killed. The effect of pulsed RF lesions on cerebral tissue ultrastructure was studied. RESULTS: In the pulsed RF group, intracytoplasmic edema, clarity of the mitochondrial cristas and opening in the cell membrane pores were observed on the electron microscopic examination. In the conventional RF group, these findings were more prominent. In the pulsed RF group, the ratio of the effected neurons was 5.5% on light microscopic examination. In the conventional RF group, the ratio of the effected neurons was 14.26% and central necrosis was observed additionally. DISCUSSION: Pulsed RF caused ultrastructural changes in the neurons. The pulsed RF may possibly cause a depression on the cell membrane potential by opening the cell membrane pores and resulting in the ion entrance into the cell cytoplasm and intracytoplasmic edema. However, it seems that all these changes were reversible. PMID- 17288743 TI - Ictal SPECT in supplementary motor area seizures. AB - OBJECTIVES: We used ictal single photon emission computed tomography (SPECT) to clarify the propagation pathways of epileptic discharges in patients with supplementary motor area (SMA) seizure. METHODS: In four patients (four males, age range, 18-27 years) with SMA seizures, SPECT studies by radioisotope 99mTc ECD were performed as a preoperative evaluation. Two of the patients remained seizure-free after complete resection of the focal cortical dysplasia on magnetic resonance (MR) images including epileptic foci. In the other two patients, MR images were normal, but subdural electrode monitoring allowed for verifying the ictal onset in the left SMA. After partial resection of the SMA including epileptic foci, these patients experienced a significant (>90%) reduction of seizure frequency. Regional cerebral blood flow (rCBF) measurements obtained under ictal and interictal conditions were compared on a voxel-by-voxel basis by means of the SPM99 paired t-test option (uncorrected p<0.001). RESULTS: Significant increases in rCBF under ictal conditions were identified in the bilateral anterior cingulate cortex (ACC), the globus pallidus ipsilateral to epileptic foci and the contralateral cerebellar hemisphere. The right ACC included a cluster with a submaximum in the right primary sensorimotor area. DISCUSSION: In patients with SMA seizures, the hyperperfusion areas of ictal SPECT did not localize within the SMA but spread to the adjacent cortex such as the ACC and sensorimotor cortex ipsilateral to epileptic foci. Additionally, the epileptic discharges propagated to the remote areas such as the globus pallidus and cerebellum. We caution that ictal SPECT localization in patients with SMA seizures is not always concordant to epileptic focus but reveals already spread seizure activities. PMID- 17288744 TI - Initial motor impairment influences activation pattern of motor recovery. AB - OBJECTIVES: We investigated the functional magnetic resonance imaging (fMRI) activation pattern of a motor task in patients with acute subcortical lesions to examine the relationship between activation pattern and recovery of motor impairment. METHODS: Five patients (one with subcortical infarction and four with thalamic hemorrhage) were examined using fMRI 1 month after the insult. Impairment was assessed by the Medical Research Council motor strength classification (MRC). One patient with severe motor deficits was also studied at 4 months when her motor deficits improved up to MRC grade 4. RESULTS: Three patients with relatively mild deficits (MRC grade 3 or 4) at their onsets, improved fully up to grade 5 within 1 month. FMRI performed at 1 month showed activation in the contralateral primary motor cortex and supplementary motor area (SMA), but no significant activation was seen on the ipsilateral unaffected side. Two patients with severe motor impairment (MRC grade 1) improved up to 3 and 4 of MRC at 1 month or later. They showed activation of the ipsilateral premotor area as well as contralateral primary motor cortex and SMA. One of them, whose severe motor deficit improved at 4 month, also showed activation of the ipsilateral postcentral gyrus and the activated area expanded longitudinally corresponding with her functional recovery. DISCUSSION: Our study demonstrates that the fMRI pattern varies according to functional recovery, suggesting the importance of the ipsilateral premotor area and postcentral gyrus especially for those patients with severe motor impairment initially. PMID- 17288745 TI - Plasma homocysteine levels in patients treated with levodopa: motor and cognitive associations. AB - OBJECTIVE: The aim of this study was to determine whether hyperhomocysteinemia caused by levodopa used in idiopathic Parkinson's disease (IPD) is associated with cognitive or physical impairments. The role of folate and vitamin B12 levels in this context was also ascertained. METHODS: Thirty-nine patients who had been followed with the diagnosis of IPD in our clinic for > 2 years and 28 healthy control subjects with similar demographic features were included in the study. The homocysteine, folic acid and vitamin B12 levels and the results of the short test of mental status (STMS) and the clock drawing test of IPD patients were compared with those of the controls. Subsequently, the patients with a homocysteine level of >14 micromol/l were compared with those having a homocysteine level of <14 micromol/l by means of detailed neuropsychometric test batteries. RESULTS: Homocysteine levels were significantly higher in the patient group in comparison with the controls. There was a negative correlation between hyperhomocysteinemia and the levels of vitamin B12 and folate. On the other hand, a positive correlation between hyperhomocysteinemia and the levodopa dose was detected. There was a positive correlation between hyperhomocysteinemia and unified Parkinson's disease rating scale (UPDRS) motor section. The critical dose of levodopa was observed to be 300 mg/d. In terms of cognitive and frontal functions, no significant difference was detected between the patients and control group. The subgroup with a homocysteine level of >14 micromol/l had a significantly poorer performance in frontal and memory tests. DISCUSSION: In patients with IPD who are detected to have hyperhomocysteinemia, the assessment of the cognitive performance, folic acid and vitamin B12 levels and the supplementation of folic acid and vitamin B12 to the treatment regimen might be appropriate. PMID- 17288746 TI - The effect of mexiletine on the level of lipid peroxidation and apoptosis of endothelium following experimental subarachnoid hemorrhage. AB - OBJECTIVE: The role of apoptosis in etiopathogenesis of vasospasm is not clearly understood yet. It is widely accepted that protection of the endothelial cells from the process of apoptosis could have beneficial effects on cerebral vasospasm after subarachnoid hemorrhage (SAH). Mexiletine blocks sodium and calcium channels and activates ATP-sensitive K(+) channels. Moreover, mexiletine is known to have potent antioxidant effects through inhibiting free-radical production. METHODS: Twenty-one rabbits were allocated into three groups randomly. Group I was sham operated group (n=7). SAH occurred but no medication was given to the Group II rabbits (SAH only group) (n=7). Mexiletine (50 mg/kg, b.i.d., i.p.) was administered just before SAH and continued until 48 hours following SAH to the Group III rabbits (Mexiletine treated group) (n=7). The ApopTag peroxidase in situ apoptosis detection kit (Serologicals Corporation, former Intergen) was used to demonstrate apoptosis in a cross section of basillary arteries. Thiobarbituric acid reactive material was used to determine the lipid peroxidation levels. RESULTS: There was a statistically significant difference between lipid peroxidation product levels of the control and SAH only groups (p<0.05). The level of lipid peroxidation production in Mexiletine treated group was significantly lower compared with SAH only group (p<0.05) but not significantly higher than the control group (p>0.05). DISCUSSION: In the present study we investigated the antioxidant action of mexiletine on apoptosis of endothelium following a rabbit SAH model. This experimental study directly suggested that lipid peroxidation is an important step in development of apoptosis in endothelial cells and prevention of structural integrity of endothelial cell should play a beneficial role in attenuation of cerebral vasospasm. Mexiletine treatment prevented the increase in lipid peroxidation and cerebral vasospasm. Examination of endothelial cells by staining specific for apoptosis demonstrated significant protection of cell integrity in the treated group. PMID- 17288747 TI - Regional cerebral (18)FDG uptake during subarachnoid hemorrhage induced vasospasm. AB - OBJECTIVES: The aim was to elucidate whether aneurysmal subarachnoid hemorrhage (SAH)-induced vasospasm induces changes of regional glucose uptake in surgically treated, asymptomatic cases. METHODS: (18)FDG uptake (standardized uptake value, SUV) was analysed with PET in eight surgically treated aneurismal patients with a mean middle cerebral artery flow velocity >120 cm/seconds measured with transcranial Doppler ultrasound. Data were compared with a healthy control group using Statistical Parametric Mapping (SPM99b). RESULTS: Six of the eight patients had no focal neurological signs. The inhomogeneous bilateral increase in SUV (p<0.0001) was asymmetrical, with an almost 70% larger volume on the operated side. Reduced glucose uptake was found in the frontal and temporobasal regions of the two patients with neurological deficits (p<0.0001); the affected volume was 40% larger on the operated side. DISCUSSION: SAH-induced vasospasm results in widespread increase of glucose uptake-probably reflecting increased glycolysis. This was earlier than neurological focal signs appear. Decreased glucose uptake can be detected in severe cases of vasospasm reflected by neurological deficit. Although the changes are more prominent where surgery had taken place our results suggest that not only the surgery, but also subarachnoid blood might have resulted in our findings. PMID- 17288748 TI - Age-related changes in cerebral hemodynamics and their correlations with cardiac autonomic functions. AB - OBJECTIVES: This study was designed to evaluate the correlations between cerebral hemodynamics and cardiac autonomic functions in aging process using transfer function techniques. METHODS: Arterial blood pressure (ABP), middle cerebral artery flow velocity (MCAFV) detected by transcranial Doppler sonography and electrocardiogram were recorded simultaneously in 20 young (27.5 +/- 0.9 years) and 20 middle-old-aged (54.3 +/- 1.5 years) healthy volunteers. Variability of ABP, MCAFV and heart rate (HR) were diffracted into very low (VLF, 0.016-0.04 Hz), low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) components. Cerebral vasomotor reserve was quantified by specific ABP-MCAFV transfer function measurements. RESULTS: The young group had significantly higher LF transfer phase and HF transfer magnitudes of ABP-MCAFV transfer function; higher HF powers of HR variability; and higher baroreflex sensitivity than those of the middle-old-aged group. LF phase and HF magnitude of ABP-MCAFV transfer function were positively correlated with HF powers of HR variability. DISCUSSION: Although aging process is not obviously associated with changes in the static values of ABP, MCAFV and HR in this study, it is accompanied by significant declines in cerebral vasomotor reserve, cardiac vagal activity and baroreflex sensitivity. Besides, age-related changes in cerebral vasomotor reserve are positively related to those in cardiac vagal activity. PMID- 17288749 TI - Doppler ultrasonographic measurement of blood flow velocities in major cerebral arteries of the rat using triplex mode. AB - OBJECTIVE: In patients with subarachnoid hemorrhage, delayed cerebral ischemia caused by vasospasm of major cerebral arteries is an important factor of morbidity. While Doppler ultrasonographic monitoring of blood flow velocities is a routine bedside examination in these patients, the current rodent models of vasospasm do not include this technique. In this article, we present an extended craniectomy in rats, which allows for direct angle-corrected Doppler ultrasonographic examination of major cerebral vessels. METHODS: Ultrasonographic examination employs a triplex window displaying simultaneously B-mode, colour coded vessel rendering and Doppler-assessment of blood flow velocity. The animals receive anesthesia for the measurements, which are repeated several times a week. RESULTS: Mean flow velocities determined by 116 measurements in 16 animals are (cm/s): truncus cerebri anterius: 8.16, arteria pericallosa: 7.49, arteries (Aa.) cerebri anteriores: 7.76, Aa. carotides: 8.76, Aa. cerebri mediae: 8.55, Aa. cerebri posteriores: 5.27, artery (A.) basilaris: 5.90. DISCUSSION: We describe the direct intravital detection of blood flow velocities in major cerebral vessels of the rat. The technique allows for simultaneous visualization of intracranial structures, vessel diameters and cerebral blood flow velocities. Our ongoing research focuses on determining normal values in a larger population of animals and examining the feasibility of the technique regarding the rodent model of vasospasm. PMID- 17288751 TI - [Hope and challenge of drug-eluting stent]. PMID- 17288750 TI - Endovascular thrombolysis and stenting of a middle cerebral artery occlusion beyond 6 hours post-attack: special reference to the usefulness of diffusion perfusion MRI. AB - Intra-arterial thrombolysis and percutaneous angioplasty is feasible in patients with acute middle cerebral artery (MCA) occlusion limited to 6 hours post-ictus, but there are some limitations such as reocclusion or hemorrhagic complications. In this report, we describe a stent placement in the treatment of a refractory artherothrombotic MCA occlusion beyond 6 hours of symptom onset. A 57-year-old man presented with a progressive left-sided weakness and verbal disturbance resulting from an acute thrombotic occlusion of the right MCA superimposed on severe proximal atheromatous stenosis. Diffusion-perfusion magnetic resonance imaging (MRI) demonstrated the significant diffusion-perfusion mismatch. After chemical and mechanical thrombolysis of the clot, balloon angioplasty of the underlying MCA stenosis was performed 2 days post-attack, without significant angiographic improvement. Percutaneous endovascular deployment of a stent (Driver 2.5 x 12 mm, MTI, Irvine, CA) was subsequently performed, with excellent angiographic results. Follow-up diffusion-perfusion MRI showed improved perfusion in the hypoperfused area. The patient's National Institutes of Health Stroke Scale (NIHSS) score was increased from 12 to 3. Clot thrombolysis and subsequent stenting in patients with refractory proximal MCA occlusion is feasible and allows for a significant reduction in the amount of thrombolytic drug required. In selective patients with acute MCA occlusion, the therapeutic window for recanalization procedures can be safely and effectively extended beyond the 'traditional 6 hours'. Diffusion-perfusion MRI in acute MCA occlusion is important for indication of therapy. PMID- 17288752 TI - [Drug-eluting stent: is it safe?]. PMID- 17288753 TI - [Beyond the numerals: primary reports from Registry of PCI In China (ROPIC)]. AB - OBJECTIVE: The purpose of this registry is to collect data on percutaneous coronary interventions (PCI) performed in various provinces in mainland China in 2005. METHODS: Questionnaires were send to all hospitals in China and data on PCI, PCI case numbers and type of stents were collected. RESULTS: (1) PCI is available in 754 hospitals among the 30 provinces and there are more than 50 hospitals performing PCI in 4 provinces: Shandong (70), Beijing (60), Guangdong (60) and Shanghai (50); (2) A total of 95 912 PCIs were performed among the 30 provinces and about 50% of these procedures were finished in five provinces (Beijing: 20%, Shanghai: 8.9%, Shandong: 7.6%, Liaoning: 6.1% and Shanxi 6.0%; (3) PCI numbers were more 1000 in 7 hospitals, between 500 - 999 in 13 hospitals, between 300 - 499 in 41 hospitals, between 100 - 299 in 149 hospitals and less than 100 in more than 50% of all hospitals; (4) In several regions with higher GDP such as Jiangsu Province, Zhejiang Province, Guangdong Province, Shandong Province and Hainan Province, the rate of PCI/total population is significantly lower than other regions with comparable GDP and there is a potential for higher PCI numbers in the future; (5)Around 60% stents implanted were drug eluting stents. CONCLUSION: PCI procedures is popular in mainland China now, especially in regions with higher GDP. Around 60% implanted stents were drug eluting stents. PMID- 17288754 TI - [Safety and efficacy comparison between rapamycin-eluting stent with biodegradable polymer or permanent polymer in patients with coronary artery disease]. AB - OBJECTIVE: To evaluate the safety and efficacy of rapamycin-eluting stent with biodegradable polymer (EXCEL) or permanent polymer (Cypher) in patients with coronary artery disease (CAD). METHODS: In this prospective, non-random and comparative study, 60 patients with CAD were divided into EXCEL group (n = 32) and Cypher group (n = 28). The coronary angiography (CAG) and stenting procedure were identical. The safety and efficacy of EXCEL stent was evaluated by major adverse cardiac events (MACE), restenosis rate and percent diameter stenosis rate as well as late luminal loss (LLL) at six months post stenting. RESULTS: During follow-up (mean: 6.04 +/- 2.12 months), there was no MACE in the two groups. Quantitative coronary angiography (QCA) data at 6.0 +/- 2.1 months post stenting were available in 27 patients (84.38%) in EXCEL group and 10 patients (35.71%) in Cypher group. Restenosis rate was zero in both groups. Percent diameter stenosis rate (5.98% +/- 5.52% vs. 5.21% +/- 6.3%) and LLL (-0.02 +/- 0.09 mm vs. -0.01 +/ 0.07 mm) were similar between the 2 groups. CONCLUSIONS: EXCEL stent was safe for the treatment of CAD and comparable as Cypher stent in preventing MACE and restenosis at 6 months post stenting. PMID- 17288755 TI - [Clinical characteristics and management of patients with acute or subacute coronary in-stent thrombosis]. AB - OBJECTIVE: To determine risk factors and evaluate the efficacy of emergent PCI for acute or subacute coronary in-stent thrombosis. METHODS: Baseline and follow up data of 6977 patients who underwent stent implantation in our institution between January 2000 and May 2006 were analyzed. RESULTS: Of 6977 patients, acute or subacute coronary in-stent thrombosis was confirmed in 52 (0.75%) patients by coronary angiogram. The in-stent thrombosis occurred between 30 minutes to 20 days post PCI (mean 3.6 +/- 4.2 days). Predictive factors for in-stent thrombosis showed by multivariate analysis were AMI, B2/C type lesions, multi-vessel diseases, heart failure and target lesions on left anterior descending artery (LAD). Among these 52 patients, 43 presented recurrent chest pain or ST elevation AMI, 6 suffered from cardiac arrests, 1 manifested hypotension and 2 showed no typical clinical symptoms and were diagnosed during scheduled PCI for other diseased vessels. Emergent coronary angiogram evidenced total thrombotic occlusion in 48 patients and 70% - 95% thrombotic stenosis in 4 patients. All 52 patients were treated with emergent PCI. Forty-seven patients survived and 5 patients died (mortality 9.6%). CONCLUSION: The risk of developing in-stent thrombosis was higher in patients with AMI, B2/C type lesions, multi-vessel diseases, heart failure and target lesions on LAD. Emergent PCI is the most effective method for treating in-stent thrombosis and should be carried out as early as possible in order to improve outcomes of this severe complication post stenting. PMID- 17288756 TI - [Clinical and angiographic outcome in patients undergoing elective bare- metal stenting or drug-eluting stenting for total occlusion lesion]. AB - OBJECTIVE: To compare the clinical and angiographic outcome in patients with total occlusion lesion treated with drug-eluting stent (DES) or bare-metal stent (BMS). METHODS: A total of 155 (138 males) consecutive patients with total occlusion lesion underwent successful revascularization with DES (n = 74) or BMS (n = 81) in our hospital were included in this study. All patients received aspirin 300 mg and clopidogrel 75 mg once daily for at least 3 months after the procedure. Clinical and angiographic follow-up were completed in all patients at 6 months post stenting. RESULTS: Demographic data between the two groups were similar except there was more diabetic patients in DES group (33.8% vs. 18.5%, P < 0.05). A total of 232 stents for 159 target lesions (77 treated with DES, 82 treated with BMS) were implanted. There were 85.4% C ACC/AHA type lesions and 17.0% lesions were treated with overlapping stents. Six months post stenting, the incidence of restenosis (15.6% vs. 41.5%, P < 0.001), the cumulative rate of major adverse cardiac events (MACE) (1.4% vs. 11.1%, P = 0.032) and TLR (5.8% vs. 19.9%, P = 0.001) were significantly lower in DES group than that of BMS group. The incidence of local restenosis in DES group is higher in DES group than that in BMS group (58.3%, 17.6%, P < 0.001). Two DES treated patients developed late in-stent thrombosis. CONCLUSION: For patients with total occlusion lesion, the clinical and angiographic outcome 6 months post DES stenting is clearly superior to that of BMS stenting. PMID- 17288757 TI - [Effect of pre-angiography use of tirofiban in patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention]. AB - OBJECTIVE: To observe the safety and efficiency of ultra-early glycoprotein IIb/IIIa receptor blockade tirofiban use in patients with acute ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI). METHODS: From April 2005 to April 2006, 158 consecutive AMI patients (117 males, mean age of 58.8 +/- 25.2 years) were randomly received tirofiban (10 microg/kg bolus i.v. followed by 0.15 microgxkg(-1)xmin(-1) for 36 hours) before PCI in emergency room (early, n = 78) or immediately before PCI in catheterization lab (late, n = 80). Clinical and angiographic features between 2 groups before and after PCI were analyzed. RESULTS: Baseline clinical characteristics before PCI were similar between the two groups. Tirofiban was administered 39.8 minutes earlier in early group than that in the late group. The TIMI 3 flow rate (23.1% vs. 10.0%, P = 0.032) and the combined TIMI 2 or 3 flow rate (39.7% vs. 23.8%, P = 0.040) at initial angiography before PCI were significantly higher in early group than that in late group. However, TIMI 3 flow rate, myocardial Blush grade or corrected TIMI frames immediately after PCI were similar between the groups. The combined incidence of death or recurrent MI as well as bleeding complications or thrombocytopenia rate during early follow-up were similar between the groups (P > 0.05). CONCLUSIONS: Early initiation of tirofiban in patients with acute STEMI treated by primary PCI was safe. A better patency (TIMI 3 and TIMI 2-3 flow) in infarct related artery was obtained in patients with early tirofiban administration. PMID- 17288758 TI - [Morphological features of secundum atrial septal defect in adult and implications for transcatheter closure]. AB - OBJECTIVE: To study the morphological features of secundum atrial septal defect (ASD) in adult and the implications for transcatheter closure. METHODS: Transcatheter closure using Amplatzer duct occluder was performed in 272 adult patients with ASD from September 1997 to December 2005. The morphological features were evaluated by transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE). The size, length and thickness of rims, occluder diameter, the complete closure rate, residual shunt rate and complications were compared in patients with deficient and/or thin rims (Group A, n = 135) and patients with well-developed rims (Group B, n = 137). RESULTS: The complete closure rate was 97.8% (132/135) in group A and 99.3% (136/137) in group B. There were 74 cases with deficient rims, 39 cases with thin rims and 22 cases with both deficient and thin rims in group A. Gender distribution, age, operation successful rate, residual shunt rate and complication rate were similar between the 2 groups. The defect diameters measured by TTE (18.9 +/- 5.5 mm vs. 16.5 +/- 4.8 mm, P < 0.01), TEE (22.7 +/- 5.0 mm vs. 20.0 +/- 5.5 mm, P < 0.01) and occluder diameters used (29.1 +/- 5.7 mm vs. 26.0 +/- 5.9 mm, P < 0.01) were significantly larger in groups A than that in group B. The systolic pulmonary artery pressure was also significantly higher in groups A than that in groups B (36.9 +/- 11.9 mm Hg vs. 32.6 +/- 9.1 mm Hg, P < 0.01). There are significant correlations between occluder diameters and defects measured by either TTE or TEE in both groups (group A, TTE: r = 0.709, TEE: r = 0.850; group B, TTE: r = 0.716, TEE: r = 0.915, P all < 0.01). CONCLUSIONS: Poor residual rims were found in around 50% of adult patients with ASD. Transcatheter closure of these defects could be successfully performed with larger occluders. The defect diameters measured by TTE and TEE, especially the latter, could guide the occluder selection. PMID- 17288759 TI - [Early complications following transcatheter occlusion of perimembranous ventricular septal defects in children]. AB - OBJECTIVE: To evaluate the early complications during and after transcatheter closure of perimembranous ventricular septal defects (PMVSDs) in children. METHODS: A total of 223 patients received transcatheter closure of PMVSDs from March 2002 to December 2005 in our hospital were included in this retrospective study. RESULTS: The overall complications rate was 26.9% (60/223). Major complications occurred in 9 patients (4.0%) including III degrees atrioventricular block (AVB) in 2 (0.9%), hemolysis in 3 (1.3%) and surgical interventions in 4 patients (1.8%) because of device malposition (1), mild aortic regurgitation (2) and device embolization (1) and all 4 patients recovered without further complications. The 2 patients with III degrees AVB were completely recovered to normal sinus rhythm after 7 days treatment with temporary pacemaker and corticosteroid. Hemolysis in 3 patients disappeared after corticosteroid treatment. Minor complications occurred in 51 patients (22.8%) including bundle branch block (BBB) in 37 (16.6%), first-degree AVB in 2 (0.9%), second-degree AVB in 1 (0.4%), new-onset mild aortic regurgitation in 5 (2.2%) and new-onset mild to moderate tricuspid regurgitation in 6 patients (2.6%). Except for right bundle branch blocks, other BBBs were treated with albumin and corticosteroid and completely recovered. No treatment was applied for new-onset valve regurgitations. There was no death in all 223 patients. CONCLUSIONS: Early complications post PMVSDs in children are mostly minor with good prognosis and the prognosis for major complications post PMVSDs is good after proper treatment. PMID- 17288763 TI - [The relationship between TIMI (thrombolysis in myocardial infarction) risk score and efficacy of conservative or interventional strategy in patients with non-ST segment elevation acute coronary syndromes]. AB - OBJECTIVE: To investigate the relationship between thrombolysis in myocardial infarction (TIMI) risk score and efficacy of different treatment strategies in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS: From Oct. 2001 to Oct. 2003, 545 consecutive patients with NSTE-ACS were randomly assigned to early conservative strategy (n = 284) or early invasive strategy group (n = 261). The combined cardiovascular events (a combination of cardiac death, nonfatal myocardial infarction, nonfatal heart failure and re hospital admission due to recurrent ischemia angina) within 30 days and 6 months were analyzed and related to the TIMI risk score at admission. RESULTS: Rehospitalization due to recurrent ischemia angina of 30 days and the combined cardiovascular events of 30 days and 6 months were significantly lower in early invasive strategy group (3.5%, 10.0%, 21.1%) compared with early conservative strategy group (8.1%, 16.9%, 28.2%, all P < 0.05). Subgroup analysis indicated early invasive strategy could significantly decrease the 30 d incidence of the combined end point events in patients with high TIMI risk score and the 6 months incidence of the combined end point events in patients with moderate and high TIMI risk score (all P < 0.01), but the incidence was similar between the two different strategies in patients with low TIMI risk score. CONCLUSIONS: Early invasive strategy may significantly reduce combined cardiovascular events in NSTE ACS patients with moderate and high TIMI risk score compared with early conservative strategy. PMID- 17288765 TI - [Comparison between pre- and post-transplant diagnosis of end-stage dilated cardiomyopathy]. AB - OBJECTIVE: To evaluate the discrepancy between pre- and post-transplant diagnosis of end-stage dilated cardiomyopathy, a pre-transplantation diagnosis was compared with the diagnosis made after macroscopic and microscopic examination of the explanted hearts in 40 cardiac transplant recipients who had undergone cardiac transplantation at our institute. METHODS: Pre-operation echocardiograms were obtained in all patients and coronary angiogram was obtained in 9 patients who had significant risk factors for coronary heart disease (CHD). CHD was considered present when there was a 75% reduction in cross-sectional luminal area of >or= 1 major coronary artery. Idiopathic dilated cardiomyopathy (IDC) was diagnosed when ventricular dilation and global reduction in ventricular systolic function were present in the absence of any identifiable cause. IDC patients with an alcohol consumption of > 100 g/day during the last 12 months before the onset of congestive heart failure were classified as having alcoholic cardiomyopathy. The pathological diagnosis of arrhythmogenic right ventricular cardiomyopathy was formulated in the presence of gross/or histological evidence of regional or diffuse transmural fatty or fibrofatty infiltration of the right ventricular free wall. RESULTS: Before transplantation, 45.0%, 17.5%, 17.5% and 7.5% of patients were classified as IDC, CHD, alcoholic cardiomyopathy and hypertrophic cardiomyopathy. Post-transplant CHD diagnosis was made in all patients with a pre transplant diagnosis of CHD. Post-transplant CHD diagnosis was also established in 4 patients with a pre-transplant diagnosis of IDC, in 4 patients with presumptive alcoholic cardiomyopathy, in 1 patient with hypertensive cardiomyopathy and in 1 patient with a pre-transplant diagnosis of aortic valve disease. Post-transplant arrhythmogenic right ventricular cardiomyopathy diagnosis was made in 6 patients with a pre-transplant diagnosis of IDC or KaShan disease. Post-transplant giant cell myocarditis diagnosis was made in 1 patient with a pre-transplant diagnosis of IDC. CONCLUSION: Post-transplant CHD diagnosis is significantly higher than that of pre-transplant (42.5% vs. 17.5%, P < 0.05). Part of these patients might benefit from bypass surgery or PCI. Therefore, "in depth" search for a heart failure cause, especially the coronary angiography examination, should be conducted in all heart transplantation candidates due to heart failure, regardless of their clinical presentation. PMID- 17288766 TI - [Efficacy of implantable loop recorders in establishing symptom-rhythm correlation in patients with unexplained syncope]. AB - OBJECTIVE: To evaluate the efficacy of the implantable loop recorder (ILR) in establishing symptom-rhythm correlation in patients with unexplained syncope. METHODS: Implantable loop recorders (ILR, Reveal Plus(9526), Medtronic Inc.) were implanted in 10 patients [aged 14 - 78 (41 +/- 22) years, 6 female] with unexplained syncope from October 2002 to May 2005. Syncopal episodes were (4.5 +/ 1.4) patients. RESULTS: During the monitoring period [8 - 21 (15.3 +/- 3.6) months], there were 24 times syncopal episodes in 6 patients. A total of 211 arrhythmia events were documented by ILR in 7 patients and symptom-rhythm correlation could be established in these 7 patients. In 2 patients, there were no recurrent syncopes and no arrhythmia events could be recorded. In 1 patient, syncope was caused by reasons other than arrhythmia. CONCLUSION: ILR is useful in determining the presence or absence of an arrhythmia during symptoms of syncope when conventional diagnostic testing, such as electrocardiogram, Holter monitoring, and/or external loop recording, is inconclusive. PMID- 17288768 TI - [Relationship between sympathetic remodeling and electrical remodeling at infarcted border zone of rabbit with chronic myocardial infarction]. AB - OBJECTIVE: To investigate the relationship between sympathetic remodeling and electrical remodeling at the infarcted border zone (IBZ) of rabbit with chronic myocardial infarction (MI). METHODS: Thirty rabbits were randomly assigned into two groups: MI group (n = 20): ligation of the anterior descending coronary; sham operation (SO) group (n = 10): without contrary ligation. Eight weeks after surgery, transmural dispersion of repolarization (TDR) at baseline, during sympathetic nerve stimulation, TDR change (DeltaTDR) during sympathetic nerve stimulation and ventricular fibrillation threshold (VFT) were measured at the IBZ in MI group and corresponding zone in SO group. The distribution and densities of growth associated protein 43 (GAP43) and tyrosine hydroxylase (TH) positive nerves in ventricle were also detected with immunohistochemical techniques. RESULTS: Eighteen rabbits in the MI group and 10 in the SO group survived to the end of the study. The densities of GAP43 and TH at the IBZ in the MI group were significantly higher than that at the corresponding zone in the SO group (both P < 0.05). The densities of GAP43 and TH in MI rabbits positively correlated with TDR at baseline, TDR or DeltaTDR during sympathetic nerve stimulation (all P < 0.01) and both showed a weak negative correlation with VFT (r =-0.44, P = 0.07; r = -0.41, P = 0.09, respectively). CONCLUSION: Sympathetic remodeling is correlated with electrical remodeling at the IBZ in rabbits with chronic MI. PMID- 17288769 TI - [Sirolimus inhibits the differentiation, proliferation and migration of endothelial progenitor cells in vitro]. AB - OBJECTIVE: To investigate the effect of sirolimus on differentiation, proliferation, adhesion and migration of endothelial progenitor cells (EPC) in vitro. METHODS: (1) Mononuclear cells (MNC) were isolated from rat bone marrow by Ficoll density gradient centrifugation and cultured on fibronectin-coated culture dishes with or without sirolimus (0.01 - 100 ng/ml) for 12 days. (2) After 8 days cultured, attached cells were treated with sirolimus (0.1 - 200 ng/ml) or vehicle for various time points (12 h, 24 h, 48 h and 96 h). EPC were identified as adherent cells double positive stained for FITC-UEA-I and DiI-acLDL under laser confocal immunofluence microscope. EPC proliferation, migration were assayed with MTT assay and modified Boyden chamber assay respectively. RESULTS: EPC number differentiated from MNC at 12 days was significantly lower in sirolimus treated cells in a dose-dependent manner than that of vehicle-treated cells. Sirolimus also significantly inhibited the proliferative, migratory and adhesive capacity of EPC in a time and dose dependent manner. CONCLUSION: Present results suggested that sirolimus could inhibit EPC differentiation from MNC and reduce the proliferation, migration and adhesion capacities of EPC. PMID- 17288770 TI - [Relationship between aging and the number and function of bone marrow-derived endothelial progenitor cells in rats]. AB - OBJECTIVE: To investigate the relationship between aging and the number and function of bone marrow-derived endothelial progenitor cells (EPC) in rats. METHODS: The number and function of bone marrow-derived EPC were measured in 4, 10 and 18 months old rats (n = 10 in each group). Mononuclear cells (MNC) were isolated from rat bone marrow by Ficoll density gradient centrifugation and cultured for 7 days, EPC were identified as adherent cells double positive stained for FITC-UEA-I and DiI-acLDL under laser confocal immunofluence microscopy. Boyden chamber was used to determine the migration capacity of EPC and the number of recultured EPC was counted to test the adherent function of EPC. RESULT: The number (42.0 +/- 5.8 vs 30.8 +/- 4.7 vs 21.5 +/- 4.7 per field) and the migration and adhesion capacities of EPC were significantly reduced with aging. CONCLUSION: This study shows that the number and function of EPC are decreased with aging. PMID- 17288771 TI - [Effects of angiotensin II receptor antagonism on matrix metalloproteinases and fibronectin in rats with experimental myocardial infarction]. AB - OBJECTIVE: To investigate the effects of angiotensin II (AngII) receptor (AT(1), AT(2)) antagonists on myocardial matrix metalloproteinases (MMPs) and fibronectin (FN) in rats with myocardial infarction (MI). METHODS: Rat MI was induced by permanent ligation of the left coronary artery. Placebo, AT(1) receptor antagonist valsartan (10 mgxkg(-1)xd(-1)) or AT(2) receptor antagonist PD123319 (30 mgxkg(-1)xd(-1)) were given 7 days prior MI surgery. On the 1st, 3rd and 7th day after MI, Expressions of MMP-2, 3, 9, tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and FN at protein level were determined by Western blot in left ventricular free wall (LVFW), interventricular septum (IS) and right ventricular (RV). Myocardial FN distribution was also assayed by immunofluorescence. RESULTS: Typical myocardial remodeling was shown in IS and LVFW 7 days after MI. MMP-2, 3, 9 expressions at protein level were significantly increased whereas TIMP-1 and FN expressions significantly decreased in IS 1, 3, 7 days post MI in a time-dependent manner compared to that of sham operated hearts. MMP-2, 3, 9 expressions was significantly increased and TIMP-1 and FN expression significantly decreased in LVFW at the 1st post MI day and maintained up to 7th post MI day compared to that of sham operated hearts. Up-regulated expressions of MMP-2, 3, 9 and down-regulated TIMP-1 and FN expressions in IS and LVFW could be significantly attenuated by valsartan but not by PD123319. Valsartan but not PD123319 also significantly reduced MI sizes (40.4% +/- 2.1% vs 49.5% +/- 2.1%, P < 0.05). CONCLUSION: AT(1) receptor antagonist involves in the pathology procession of myocardial remodeling and might lead to the development and progression of congestive heart failure by the increasing expressions of MMP-2, 3, 9, which contribute to degradative extracellular matrix FN in myocardium. PMID- 17288772 TI - [Electrophysiological effects of acehytisine hydrochloride in a porcine model of acute coronary occlusion]. AB - OBJECTIVE: To observe the electrophysiological effect of Acehytisine Hydrochloride (AHH) in Wu Zhi Shan (WZS) micropigs with experimental acute coronary occlusion. METHODS: Adult WZS micropigs were randomized into group A: coronary ligation with AHH infusion (n = 9); group B: AHH infusion without coronary ligation (n = 9) and group C: coronary ligation with saline (NS) infusion (n = 9). Surface ECGs and cardiac electrophysiological data including atrium, atrium-ventricle junction and ventricle electrograms were collected by programmed electrical stimulation at ischemic baseline and after AHH (or NS) infusion. RESULTS: Compared to animals treated with AHH without ischemia, VARC ERP was significantly increased while QT, QTc intervals, VRRP and VFRP were significantly reduced in ischemic animals treated with AHH. Compared to ischemic animals treated with saline, AHH prolongs the P-wave duration and PR interval, shortens QTc interval, prolongs ARP and AEP, also prolongs V-A reverse conduction time and VARC-ERP but shortens VFRP. No proarrhythmia effect was found in both AHH treated groups. CONCLUSION: AHH resulted in significant electrophysiological effects on this porcine acute coronary ischemic model. PMID- 17288777 TI - [The current clinical application of percutaneous heart valve replacement]. PMID- 17288778 TI - [Application of cellular tracking technique in stem cells transplantation for heart disease]. PMID- 17288780 TI - [The research on chronic obstructive pulmonary disease more intensive, the prospect more promising]. PMID- 17288781 TI - [Future therapies for chronic obstructive pulmonary disease]. PMID- 17288782 TI - [Assessing the prognosis in patients with chronic obstructive pulmonary disease]. PMID- 17288783 TI - [Potential therapy for mucus hypersecretion in chronic obstructive pulmonary disease]. PMID- 17288784 TI - [Regulation of mucosal immunity by airway epithelium: the interleukin-17A paradigm]. PMID- 17288785 TI - [Cardiovascular and cerebrovascular disease prevention: pay attention to sleep disordered breathing]. PMID- 17288787 TI - [Endoscopic third ventriculostomy in treatment of obstructive hydrocephalus]. AB - OBJECTIVE: To explore the effects, influencing factors, and complications of endoscopic third ventriculostomy for obstructive hydrocephalus. METHODS: The clinical data of 55 patients with obstructive hydrocephalus, 29 males and 26 females, aged 18.4 (6 months - 59 years), who underwent endoscopic third ventriculostomy were analyzed retrospectively. RESULTS: Endoscopic third ventriculostomy was performed successfully in 54 patients, and one patient failed to undergo endoscopic third ventriculostomy because of densely distributed blood vessels at the bottom of the third ventricle. Satisfying post-operative results were obtained in 50 cases and no effect was seen in 4 cases that underwent V-P shunt 3 months later. Subdural hygroma occurred in 4 of the 55 cases, subscale hydrops in 8 cases, post-operative fever in 4 cases, epilepsy in 1 case, and epidural hemorrhage in 1 case. CONCLUSION: Endoscopic third ventriculostomy is safe and effective in the treatment of obstructive hydrocephalus. PMID- 17288786 TI - [Clinical and molecular genetic features of 17alpha-hydroxylase deficiency: study of a case]. AB - OBJECTIVE: To study the clinical and molecular genetic features of 17alpha hydroxylase deficiency and treatment of femoral neck fracture complicated therein. METHODS: A patient with 17alpha-hydroxylase deficiency with femoral neck fracture, with social sex as female, aged 19, underwent thorough clinical assessment, including history collection, physical examination, and laboratory test. Hormonal replacement therapy was applied and closed replacement was performed on the fractured femoral neck. Molecular genetic method was adopted to explore the gene mutation. RESULTS: The patient was diagnosed as 17alpha hydroxylase deficiency according to clinical assessment. Under spinal anesthesia, the displaced femoral neck was reduced closely and fixed using 3 cannulated screws. Ten-month follow-up showed that the function of the injured hip was recovered. Genetic examination showed homozygous mutation in the exon 6: 6436 - 6438 (TAC-->AA), causing amino acid missense mutation Y329K and 418X. CONCLUSION: Femoral neck fracture in 17alpha-hydroxylase deficiency patient can be treated successfully by operative method. 6436 - 6438 (TAC-->AA) mutation in CYP17A1 gene may be a prevalent mutation causing 17alpha-hydroxylase deficiency in China. PMID- 17288788 TI - [Microsurgical treatment of trigeminal neurinomas with middle fossa extradural approach]. AB - OBJECTIVE: To investigate the effect of microsurgical treatment of trigeminal neurinomas with middle fossa extradural approach. METHODS: Between January 1996 and December 2005, 27 patients with trigeminal schwannomas were treated by middle fossa extradural approach. The clinical data were retrospectively analyzed. RESULTS: Total resection was achieved in 25 patients and subtotal resection in the other 2 patients. The cranial nerve deficits were improved in 18 patients, unchanged in 4 patients and worsened in 5 patients postoperatively. New Incomplete paralysis of cranial nerve were observed in 4 patients. Cerebrospinal fluid leakages and bacterial meningitis occurred in 2 cases, which were cured by lumber draining and antibiotic therapy. There was not operative mortality. Twenty six patients were followed up for 6 - 48 months. Tumor recurrence was found in 1 case after 40 months and was excised again. CONCLUSION: This approach can provide better exposure of these tumors and multiple working angles with minimal brain retraction and can improve the surgical results in terms of increased complete tumor resection rate and reduced complications rate. PMID- 17288789 TI - [Quantitative detection of differential display code 3 mRNA in peripheral blood of patients with prostate cancer]. AB - OBJECTIVE: To investigate the expression of DD3 mRNA in the peripheral blood and its value in diagnostic of prostate cancer (Pca). METHODS: Thirty-five untreated Pca patients, aged 72 (53 - 83), 58 Pca patients treated with endocrinotherapy, aged 74 (53 - 86), and 59 patients with benign prostatic hyperplasia, aged 71 (48 - 85), underwent peripheral blood sample collection one week before or after digital examination. RT-PCR was used to examine the level of DD3 mRNA. The level of prostate specific antigen (PSA) was detected too. Ten healthy male frontiers, aged 33 (21 - 38), were used as controls. Receiver operating curve (ROC) was drawn to evaluate the diagnostic performance of DD3 mRNA. RESULTS: The DD3 mRNA level of the untreated Pca patients was 2741 copies/ml, significantly higher than those of the Pca patients treated with endocrinotherapy, patients with benign hyperplasia, and healthy persons (all < 24 copies, all P < 0.001). The DD3 mRNA level of the endocrinotherapy-treated Pca patients was significantly higher than those of the patients with benign hyperplasia, and healthy persons (both P < 0.001). ROC analysis showed that when the critical value was 846 copies/ml the area under curve of ROC (AUC-ROC) was 0.8233 (95% CI: 0.725 - 0.910). and the sensitivity was 74.34%, the specificity was 89.8%. The DD3 mRNA in the peripheral blood increased along with the increase of clinical staging (P < 0.01). CONCLUSION: The level of DD3 mRNA in the peripheral blood is an excellent marker for diagnosis pf Pca, and may help in monitoring of the curative effects of endocrinotherapy. PMID- 17288790 TI - [Effects of Notch-1 signaling in bone marrow mesenchymal stem cells differentiating into neurons: experiment in vitro]. AB - OBJECTIVE: To investigate the role of Notch-1 signaling in bone marrow mesenchymal stem cells (MSCs) differentiating into neurons. METHODS: Mice Notch-1 small hairpin RNA (mNotch-1 shRNA) was constructed and transfected into the MSCs obtained from the tibiae of BALB/c mice. MSCs transfected with glyceraldehyde-3 phosphate hydoxygenase (GADPH) shRNA and untransfected MSCs were used as controls. The cell survival rate was detected by ELISA. The MSCs of different groups were cultured in Neurobasal-A medium so as to be induced to differentiate into neurons. Apoptosis of the MSCs was detected by TUNEL. RESULTS: After induction of 6 days the MSCs transfected with mNotch-1 shRNA displayed typical neuronal morphology and high expression of neuron-specific markers: nestin, neuron-specific enolase (NSE), neurofilament 200 (NF 200), and Notch-1 protein, however, gilal fibrillary acidic protein (GFAP), the glia-specific marker, was not detected. The percentage of apoptotic cells in the MSCs transfected with mNotch-1 shRNA was 13.3% +/- 2.3%, significantly higher than those of the MSCs transfected with mGAPH shRNA and untransfected MSCs (4.7% +/- 0.5% and 4.5% +/- 0.4%, both P < 0.01). CONCLUSION: Block of the Notch signal pathway may increase the differentiation of MSCs into neurons. PMID- 17288791 TI - [Effects of insulin receptor substrate-1 and its serine phosphorylation and tyrosine phosphorylation on insulin resistance in skeletal muscle cells in the state of sepsis: experiment with rats]. AB - OBJECTIVE: To investigate the effects of insulin receptor substrate (IRS)-1 and its serine (Ser)(307) phosphorylation and tyrosine (Tyr) phosphorylation on insulin resistance in skeletal muscle cells in the state of sepsis. METHODS: 120 SD rats were randomly divided into 3 groups: 10% group, with 10% of the total cecal length ligated and punctured without use of antibiotic so as to make sepsis model; 30% group, with 30% of the total cecal length ligated and punctured; and control group, undergoing sham operation. Fasting venous blood samples were collected before the operation to detect the fasting plasma glucose (FPG). 0, 8, 16, 24, and 48 hours after the operation 8 rats in each group underwent fasting of food and without fasting of water for 8 hours, i.e., until the 8 th, 16 th, 24 th, 48 th, and 72 nd hours after the operation. Then the rats underwent anesthesia, with blood sample from the vena cava and specimen of gastrocnemius of the hind leg collected, and then killed. The levels of FPG, fasting plasma insulin (FINS), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were measured. HOMA method was used to calculate the insulin resistance index (Ig IRI). Immunohistochemistry was used to quantitatively examine the IRS-1 protein and its Ser(307) phosphorylation and Tyr phosphorylation in the gastrocnemius. Western blotting and immunoprecipitation were used to semi-quantitatively examine the changes in contents of IRS-1 and its Ser(307) phosphorylation and Tyr phosphorylation in the gastrocnemius respectively. RESULTS: The survival rates at different time points of the control group were all 100%, all significantly higher than those of the other 2 groups (all P < 0.01), and those of the 10% group were all significantly higher than those of the 30% group (all P < 0.01). The levels of TNF-alpha and IL-6 of the 10% and 30% groups at different time points were all significantly higher than those of the control group (all P < 0.01), and those of the 30% group were all significantly higher than those of the 10% group (all P < 0.01). The FPG, FINS, and IgIRI were not significantly different among the 3 groups before the operation, and those of the 10% and 30% groups at different time points after operation were all significantly higher than those of the control group (all P < 0.01) and peaked 8 h after the operation, with those of the 30% group all significantly higher than those of the 10% group (all P < 0.01). The degree of increase of FINS was remarkably higher than that of FPG. IRS-1 was positive and located in the cytoplasm of the gastrocnemius cells in both the control and 30% groups; IRS-1 Tyr phosphorylation was positive in the control group and sporadic positive in the 30% group. IRS-1 Ser(307) was negative in the control group and strong positive in the 30% group. Semi-quantitative examination showed that the IRS-1 level at different time points after operation of the 30% group were not significantly different from those of the control group (all P > 0.05), and IRS-1 Tyr phosphorylation degrees at different time points of the 30% group were all significantly lower than those of the control group (all P < 0.01), and the IRS-1 Ser(307) phosphorylation at different time points of the 30% group were all significantly higher than those of the control group (all P < 0.01). Spearman correlation analysis showed that IgIRI was significantly negatively correlated with IRS-1 Tyr phosphorylation (r = -0.957, P < 0.01), and significantly positively correlated with IRS-1 Ser(307) phosphorylation (r = -0.955, P < 0.01). CONCLUSION: Under the status of sepsis the IRS-1 content in the skeletal muscle cells is unchanged, the level of IRS-1 Tyr phosphorylation level is decreased, and the IRS-1 Ser phosphorylation is increased. The degrees of such changes are closely related with the degree of insulin resistance. PMID- 17288792 TI - [Genotype of TEM- and SHV-type beta-lactamase producing Klebsiella pneumoniae in Guangzhou area]. AB - OBJECTIVE: To determine the prevalence and genotypes of TEM- and SHV-type beta lactamase-producing Klebsiella pneumoniae in Guangzhou area. METHODS: Genotype determination of TEM- and SHV-type beta-lactamases were performed by PCR amplification followed by denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing among 57 strain of klebsiella pneumonia obtained from the hospitals in Guangzhou. RESULTS: The genes bla(TEM) and bla(SHV) were amplified from all strains. TEM-116 type ESBLs were found in 56.14% (32/57) of the isolates. SHV-12 (n = 19), -11 (n = 11), -2a (n = 6), -28 (n = 4), -26 (n = 1), -33 (n = 1) and five novel SHV-type beta-lactamases were identified among the SHV-type beta-lactamases. These novel enzymes were designated from SHV-64, -65, 66, -67 and SHV-69, which derived from SHV-1 beta-lactamase or SHV-12 ESBL. A total of 94.74% of the isolates (54/57) produced both TEM- and SHV-type beta lactamases simultaneously, in which 13.0% were TEM-116 and SHV-12 (n = 12). CONCLUSION: TEM-116 and SHV-12 are the predominant TEM- and SHV-type genotypes of Klebsiella pneumoniae producing beta-lactamases in Guangzhou. This area is confronted with the prevalence of the phenotypes of Klebsiella pneumoniae that simultaneously produce TEM- and SHV-type beta-lactamases. PMID- 17288802 TI - [Strategy for diagnosis and treatment of infections after hemopoietic stem cell transplantation]. PMID- 17288804 TI - [Etiology, diagnosis, and treatment of post-transplant lymphoproliferative disorders]. PMID- 17288805 TI - [Some experience on the diagnosis of "fever of unknown origin"]. PMID- 17288806 TI - [Killer cell immunoglobulin receptor plays an important role in cord blood transplantation for leukemia]. AB - OBJECTIVE: To investigate the role of killer cell immunoglobulin receptor (KIR) plays in treatment of leukemia by cord blood transplantation (CBT). METHODS: Peripheral blood samples were collected from 23 patients receiving CBT, and corresponding cord blood samples were collected too. Polymerase chain reaction with sequence-specific primers was used to examine the genotypes of KIR and HLA Cw of the samples. The rates of engraftment, relapse, and survival were followed up. RESULTS: Polymorphism of KIR genotype was found in the 23 cord blood samples. In the 17 cases of acute myelocytic leukemia (AML), the engraftment rate and overall survival rate of the donors/recipients with KIR/JHLA-C mismatch was 65% and 70%, both higher than those of the KIR/HLA-C matched group (50% and 50% respectively), and the relapse rate of those with KIR/JHLA-C mismatch was 9%, lower than that of the KIR/HLA-C matched group (16%). The engraftment rate and overall survival rate of those with homo-expression of HLA-Cw1 or Cw2 were 65% and 70% respectively, both higher than those of the patients with double expression (50% and 50% respectively). There was no significant difference in overall survival rate between the HLA-Cw8 (+) and HLA-Cw8 (-) groups. Four cases with the co-expression of KIR2DL2 and KIR2DS2 all survived disease-free. CONCLUSION: KIR plays an important role in CBT. KIR/HLA-C mismatch, homo expression of HLA-Cw1 or Cw2, and co-expression of KIR2DL2 and KIR2DS2 may predict good prognosis for CBT. PMID- 17288808 TI - [Polymorphism of human leukocyte antigen-A, B, and DRB1 genes in bone marrow registry donors of Shaanxi province analysis of 14 006 cases]. AB - OBJECTIVE: To analyze the polymorphism of human leukocyte antigen(HLA)-A, B, and DRB1 genes in Shaanxi province, China. METHODS: Peripheral blood samples were collected from 14 006 unrelated healthy voluntary bone marrow registry donors on Shaanxi province, aged 18 - 45, with a male to female ratio of nearly 1:1. Polymerase chain reaction sequence specific primer (PCR-SSP), polymerase chain reaction sequence specific oligonucleotide probes (PCR-SSO), and sequencing-based test (SBT) was used to analyze the polymorphism of HLA-A, B, and DRB1 genes. RESULTS: In these 14 006 unrelated donors, 18, 40 and 15 HLA alleles were identified on the HLA-A, B, and DRB1 loci respectively, including HLA-A25, B42, B53, B73, and DR3 that were rarely reported in Han population. The gene frequencies of HLA-A*02, A*11, A*24, A*33, B*13, B*46, B*4001 group (B60), B*1501 group (B62), DRB1*15, DRB1*09, DRB1*04, and DRB1*12 were all significantly higher in the Shaanxi population. Two novel alleles were identified and officially assigned by the WHO Nomenclature Committee as A*0290 and B*4814. CONCLUSION: The characteristics of the polymorphism of HLA-A, B, and DRB1 genes in Shaanxi province were established which will be helpful for patients to find matched donors and establish the foundation for further studying population genetics and HLA-related diseases. PMID- 17288807 TI - [The effect of matrix metalloproteinase-9 in granulocyte colony stimulation factor-induced stem cell mobilization]. AB - OBJECTIVE: To investigate the effects of matrix metalloproteinase-9 (MMP-9) on granulocyte colony stimulation factor (G-CSF)-induced hematopoietic stem/progenitor cell (HSPC) mobilization in healthy donors of hematopoietic stem cells. METHODS: Peripheral blood (PB) samples and bone marrow (BM) blood samples were collected from 12 healthy donors of hematopoietic stem cell before and 5 days after G-CSF-induced mobilization. CD34(+) cells were isolated and purified. ELISA was used to detect the protein expression of MMP-9 in the peripheral blood and BM blood of the healthy donors. The protein expression of MMP-9 in the BM blood was detected by ELISA and immunohistochemistry, and the stromal cell derived factor-1 (SDF-1) level in the BM blood was detected by ELISA. The mRNA expression of MMP-9 in the BM blood samples was detected by RT-PCR. HT1080 cells rich in MMP-9 were cultured. CD34(+) cells were co-cultured with the supernatant of HT1080 cell culture fluid. CD34(+) cells cultured in Iscove's modified Dulbecco's medium were used as control group. Fluorescence-activated cell sorter was used to detect the CXCR4 expression on the surface of the CD34(+) cells. In the transwell experiment CD34(+) cells were divided into 4 groups: control group, o-phenanthroline (MMP-9 chemical inhibitor, MPI) group, HT1080 sup group, and HT1080 + MPI group to be co-cultured with buffer, o-phenanthroline, supernatant of culture fluid of HT1080 cells, or supernatant of culture fluid of HT1080 cells Flow cytometry was used to calculate the cell migration capacity. RESULTS: The MMP-9 level of BM and PB of the healthy donors 5 days after G-CSF mobilization were 278 ng/ml +/- 34 ng/ml and 392 ng/ml +/- 284 ng/ml respectively, both significantly higher than those before G-CSF mobilization (42 ng/ml +/- 17 ng/ml and 27 ng/ml +/- 12 ng/ml respectively (P < 0.01 and P < 0.05). Western blotting showed that the SDF-1 level in the supernatant 5 days after G-CSF mobilization was 5.9 ng/ml +/- 1.0 ng/ml, significantly lower than that before G-CSF mobilization (7.2 ng/ml +/- 0.7 ng/ml, P < 0.05). The CXCR4 levels of the CD34(+) cell from both PB and BM blood were up-regulated after co-culture with the supernatant of HT1080 cells (both P < 0.05). The migration capacity of CD34(+) cells cultured in the supernatant of HT1080 cells was increased significantly (P < 0.05), however, this effect could be inhibited by MIP (P < 0.05). The PB WBC numbers of the G-CSF group and G-CSF + MPI group were 14.9 x 10(6)/L +/- 4.3 x 10(6)/L and 12.3 x 10(6)/L +/- 1.2 x 10(6)/L respectively, the PB WBC numbers of the G-CSF + MPI group was significantly lower than that of the G-CSF group (P < 0.05), however, significantly higher than that of the negative control group (6.8 x 10(6)/L +/- 2.5 x 10(6)/L, P < 0.05). The CFU of the G-CSF group was (84 +/- 10) U/2 x 10(5) MNC, significantly higher than that of the G-CSF + MPI group, (69 +/- 3) U/2 x 10(5) MNC (P < 0.05). The BM MNC number of the G-CSF group was 12.7 x 10(6)/L +/- 0.7 x 10(6)/L, not significantly different from that of the G-CSF + MPI groups (13.1 x 10(6)/L +/- 1.3 x 10(6)/L; P > 0.05). CONCLUSION: MMP-9 probably facilitates HSPC mobilization by degrading SDF-1, up-regulating CXCR4 expression on the CD34(+) cells, and increasing the migration ability of CD34(+) cells. PMID- 17288810 TI - [Primary application of spectral karyotyping in leukemia]. AB - OBJECTIVE: To establish a spectral karyotyping (SKY) technique and explore the value of SKY in leukemia research. METHODS: SKY technique was conducted on 2 samples of peripheral blood from 2 healthy volunteers, then on the samples from 8 patients with leukemia, including chronic myelocytic leukemia (CML) and acute myelocytic leukemia (AML) confirmed by R-banding. In addition, four patients underwent dual fusion-fluorescence in situ hybridization (DF-FISH) to detect the mixed lineage leukemia (MLL), PML/RARa, and BCR/ABL fusion genes. By comparing the results of SKY, R-band karyotyping, and DF-FISH, the stability and reliability of SKY was judged. RESULTS: All 10 samples were successfully hybridized and karyotyped. The 2 cases of healthy volunteers showed normal karyotypes, thus, a specific SKY technique was successfully established. In the 8 cases of leukemia patients, SKY identified aberrations including 9q-, t (9; 22), t (15; 17) and the complex karyotype 47, XY, +9?ins (1;5) (q23;q23), t (6;7) (q23?; p13), in addition, the SKY technique detected some number abnormalities. The results of SKY confirmed the results of R-band karyotyping and DF-FISH; moreover, the SKY technique provided more accurate karyotypes. CONCLUSION: With high stability, accuracy, and sensitivity, the SKY technique established by this study can be applied in leukemia research. PMID- 17288811 TI - [Detecting biomarkers from serum in nephroblastoma patients with support vector machine]. AB - OBJECTIVE: To find new biomarkers and to establish serum protein fingerprint models for early detection and diagnosis of nephroblastoma by SELDI-TOF-MS and bioinformatics tools. METHODS: Seventy five serum samples from 35 nephroblastoma patients, 30 children's abdominal solid tumor patients, and 20 healthy children were bound to WCX2 protein chip and tested by surface enhanced laser desorption/ionization time of flight-mass spectrometry (SELDI-TOF-MS). The data of spectra were analyzed by support vector machine(SVM). RESULTS: Four peaks with m/z of 6984.5, 6455.5, 6914.0, 3256.7 were selected as potential biomarkers. The detective model combined with 2 biomarkers could separate nephroblastoma from the healthy group with a sensitivity of 100%, and a specificity of 100%. The diagnostic model combined with 2 biomarkers could separate nephroblastoma from other child's abdominal solid tumors with a sensitivity of 93.3%, and a specificity of 100%. CONCLUSION: High sensitivity and specificity achieved by this method show great potential for early diagnosis of nephroblastoma, and screening for new tumor biomarkers. PMID- 17288812 TI - [Prospective investigation of annual bone loss rate in females in Changsha city, Hunan province]. AB - OBJECTIVE: To investigate prospectively the annual bone loss rate at spine, proximal femur and distal radius in females and its relationship to relevant factors. METHODS: The bone mineral density (BMD) at anteroposterior lumber, proximal femur and distal radius in 220 women of Mawangdui Township, aged 36 - 60, was measured twice, March to April 2000 and March to April 2004, using a Hologic QDR 4500A fan beam X-ray bone densitometer. RESULTS: The annual bone loss rate was the highest during the period of 1 to 5 years since menopause, showing an annual bone loss of 1.70% at the anteroposterior spine, and 2.21%, 1.92%, and 1.56% at the femoral neck, greater trochanter, and distal radius respectively. Even before menopause bone loss was found at the femoral neck and distal radius. BMD loss at the anteroposterior spine and greater trochanter was found in the peri-menopause group. The bone loss rate was the highest in the early menopause group (1.56%/year, P < 0.01), and became lower, however, not significantly in the late menopause group (0.38%/year, P > 0.05). Age was positively correlated with the annual bone loss rates at the anteroposterior spine, greater trochanter, and distal radius (gamma = 0.223 - 0.547, P < 0.05 - 0.01), and the number of year since menopause was also positively correlated with the annual bone loss rate at anteroposterior spine and greater trochanter (gamma = 0.432 - 0.569 P < 0.05 - 0.01). However, body weight and body mass index were negatively correlated with the annual bone loss rates at the anteroposterior spine, femoral neck, and greater trochanter (gamma = 0.239 - 0.466, P < 0.05 - 0.01). CONCLUSION: Annual bone loss varies at different skeletal region. Age, years since menopause, and body weight influence the bone loss at different skeletal regions in females. PMID- 17288813 TI - [Sample targeting under stereomicroscopy can raise the detection rate of early colorectal cancer]. AB - OBJECTIVE: To establish a set of pathological diagnosis method to raise the detection rate of early colorectal cancer. METHODS: All patients with colorectal tumor underwent ordinary electron enteroscopy in 2005. The lesions larger than 10 mm underwent indigo carmine staining and magnifying electron enteroscopy to observe the pit pattern. Endoscopic mucosal resection (EMR) or endoscopic piecemeal resection (EPMR) was performed on the suspected cases of cancer, such as laterally spreading tumor (LST). The resected specimens were stained with cresyl violet and observed by stereomicroscopy to determine the pit patterns. The parts showing the pit patterns associated with early colorectal cancer were targeted and biopsy specimens collected here to undergo pathohistological examination. Routine pathological examination was conducted on the other parts of the same specimen as control. The results of these specimens were compared with those of the specimens collected by ordinary methods from the patients with colorectal tumor in 2004. RESULTS: In 2005 40 patients with colorectal tumor were suspected as with cancer and underwent EMR or EPMR of which 16 were confirmed to be with early stage colorectal cancer, including severe dysplasia by sampling targeting (40%). And the routine pathohistological examination of the randomly collected parts from these same specimens showed 15 cases of mild or moderate dysplasia and only one case of severe dysplasia, with a detection rate of 2.5%, significantly lower than that of the result of sample targeting under stereomicroscopy (P < 0.01). In 2004, out of the 54 patients suspected to be with colorectal cancer only 4 cases of early cancer, including severe dysplasia were detected with a detection rate of 7.4%, significantly than that of the year 2005 (P < 0.01). CONCLUSION: Sample targeting and localized biopsy under stereomicroscopy raises the detection rate of early colorectal cancer. PMID- 17288814 TI - [Effects of Shenfu injection on hypoxic-ischemic brain damage: experiment with neonatal rats]. AB - OBJECTIVE: To investigate the effect of Shenfu (ginseng and aconite root) injection on hypoxic-ischemic brain damage (HIBD). METHODS: Sixty 7-day-old Sprague-Dawley rats undergoing ligation of left common carotid artery and then put into a container with 8% O2 and 92% N(2) for 2 h so as to establish HIBD models, were randomly divided into 3 groups: Shenfu injection pretreatment group (since 4 days before the experiment Shenfu injection 10 ml/kg was injected intraperitoneally once a day for 4 days), Shenfu injection treatment group [Shenfu injection 10 ml/kg was injected intraperitoneally immediately after hypoxic-ischemia (HI) insult once a day for 7 days], and control group (normal saline 10 ml/mg was injected intraperitoneally immediately after HI insult once a day for 7 days). Twenty neonatal rats underwent sham operation as control group. The 4 groups were further divided into subgroups of 6 rats according to the time points: 2 hours before and 2 hours, 12 hours, 24 hours, 3 days, 7 days, 14 days, and 28 days after HI insult. 3, 7, 14, and 28 days after the HI insult the body weight was observed and the survival rate was observed 28 d after the HI insult. At different time points the rats of different subgroups were killed and their brains were taken out. Flow cytometry was used to calculate the neuron apoptosis rate in the hippocampal CA1 region. RESULTS: The body weight increase levels 3, 7, 14 and 28 days after HI insult of the control group were all significantly less than those of the sham operation group (e.g 7 days: 8.8 g +/- 2.1 g vs 14.0 g +/- 2.9 g, all P < 0.01) and the body weight increase levels 3, 7, 14, and 28 days after HI insult of the control group were all significantly less than those of the Shenfu injection pretreatment group (e.g 7 d: 11.7 g +/- 3.3 g) and Shenfu injection treatment group (e.g 7 d: 10.9 g +/- 2.7 g, P < 0.01 or P < 0.05). The survival rate 28 d after HI insult of the control group was 60%, significantly less than those of other groups (all P < 0.05), and there was no significant difference in the survival rate among the other groups (all P > 0.05). Compared with the sham operation group the neuron apoptosis rates of the hippocampal CA1 region of the Shenfu injection treatment group and Shenfu injection pretreatment group began to increase 2 hours after HI insult, peaked 24 hours after, then gradually decreased, and recovered to normal 14 days after. The neuron apoptosis rates 2, 12, 24, 72 hours, and 7 days after HI insult of the Shenfu injection pretreatment group were all significantly lower than those of the control group (e.g 24 hours: 16.0% +/- 4.2% vs 11.9% +/- 2.3% vs 18.1%, P < 0.01 or P < 0.05), and the neuron apoptosis rates 72 hours and 7 days after HI insult of the Shenfu injection treatment group were significantly lower than those of the control group. CONCLUSION: Shenfu injection can enhance the physical development and elevate the survival rate of neonatal rats with HI insult, and significantly prevents apoptosis of the hippocampus neurons from HI insult. PMID- 17288815 TI - [Comparative study of gene mutation between Chinese patients with familial and sporadic hypertrophic cardiomyopathy]. AB - OBJECTIVE: To compare the gene mutation between Chinese patients with familial and sporadic hypertrophic cardiomyopathy (HCM). METHODS: Peripheral blood samples were collected from 36 patients with familial HCM (FHCM) and 50 patients with sporadic HCM (SHCM), all un-related and from different provinces of China. PCR was used to amplify the 26 protein-coding axons of beta-myosin heavy chain (MYH7), 16 exons for cardiac troponin T (TNNT2), and 38 exons for cardiac myosin binding protein C (MYBPC3). The amplified products were sequenced and compared with the standard sequence in the genBank so as to determine the potential mutation sites. RESULTS: (1) 13 of the 36 FHCM patients (36.1%) harbored 3 different mutations in MYH7 gene: Arg663His in exon18, Glu924Lys in exon 23, and Ile736Thr in exon 20. Of the 50 SHCM patients, only 1 (2%) harbored MYH7 gene missence mutation: Ile736Thr located in exon 20. (2) TNNT2 was not identified in all SHCM patients and FHCM patients. (3) MYBPC3 was not identified in all SHCM patients. Four FHCM patients harbored 2 different mutations: Arg502Trp in exon 18 and Arg346fs in exon 13 respectively. CONCLUSION: MYH7 and MYBPC3 may be the dominant disease-causing genes in Chinese familial HCM patients; however the mutation rate of MYH7 and MYBPC3 genes is significantly lower in the SHCM patients compared with the FHCM patients. TNNT2 seems not the predominant disease causing gene in all Chinese patients with HCM. PMID- 17288816 TI - [Causes of delaying diagnosis of primary hyperaldosteronism with adrenal adenoma and strategy therefore]. AB - OBJECTIVE: To analyze the causes of delaying diagnosis of primary hyperaldosteronism with adrenal adenoma and discuss corrective strategies. METHODS: The clinical data of 267 patients of primary hyperaldosteronism with adrenal adenoma confirmed by operation 1995 - 2005 were analyzed. RESULTS: Confirmed diagnosis was made after a duration of (92 +/- 64) months (3 - 40 years) after the first visit. 78.3% of the hospitals where the patients with hypertension made their first visits were grade II hospitals, and 21.3% of them were grade III hospitals. 95.9% of the patients were diagnosed as with primary hypertension at the first visit without receiving relevant imaging examination of adrenal and endocrine examination. 87.3% of the patients with extremity weakness numbness of finger tips were diagnosed as with hypokalemia and more than 10% of them failed to receive examination of blood potassium. Adrenal adenoma was discovered by computed tomography with thin coat screening in 267 patients and by ultrasonography in 151 patients. CONCLUSION: Primary hyperaldosteronism should be considered and screened in all young patients with hypertension. Plasma aldosterone/rennin ratio is an effective mark in screening. The first choice diagnostic means for primary hyperaldosteronism should be computed tomography with screening by coat 2 - 4 mm thin. PMID- 17288827 TI - [Minimally invasive orthopaedic surgery: a point of view]. PMID- 17288818 TI - [Time dependency of factors influencing survival of hepatocellular carcinoma patients with portal vein tumor thrombosis after surgery]. AB - OBJECTIVE: To investigate the surgical outcome of the hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) after surgery and the time-dependency of the factors influencing survival. METHODS: The clinicopathological data of 382 HCC patients with macroscopic PVTT who had undergone resection of HCC were analyzed. The survival rte was calculated using Kaplan-Meier method. Stratified Cox model was used to identify the factors independently influencing the short- and long-term survival rates. RESULTS: The 1 , 2-, 3-, 5-, and 10-year survival rates of the 382 patients were 47%, 23%, 16%, 12%, and 6% respectively. The 1-, 3-, and 5-year survival rates re-calculated from the time of re-resection because of recurrence within 2 years after the first operation were 36%, 14%, and 0% 1 respectively. However, the 1-, 3-, and 5 year survival rates re-calculated from the time of re-resection because of recurrence 2 years after the first operation were 85%, 53%, and 32%, all significantly higher than those re-calculated from the time of re-resection within 2 years after the first operation (all P < 0.05). Multivariate analysis showed that portal infusion chemotherapy, serum alpha-fetoprotein < 20 microg/L and negative surgical margin were significant favorable prognostic factors within 2 years after operation. Alanine aminotransferase > 80 U/L was the only significant unfavorable factor beyond 2 years after operation. CONCLUSION: The prognosis of the patients with macroscopic PVTT who suffer from liver tumor recurrence occurring more than 2 years after the first operation is much better than those with the recurrence occurring within 2 years. Evaluation of the time dependency of risk factors may have important clinical implication in determining the therapeutic strategy. PMID- 17288828 TI - [The disaster complication of percutaneous vertebroplasty and kyphoplasty: cement leakage and its prevention]. PMID- 17288829 TI - [Review on studies of response capacity assessment instruments for public health emergencies]. PMID- 17288830 TI - [Kyphoplasty for treatment of non-osteoporotic thoracolumbar compressive fractures: analysis of 17 cases]. AB - OBJECTIVE: To evaluate the efficacy and safety of kyphoplasty for treatment of non-osteoporotic compressive fractures of thoracolumbar vertebrae. METHODS: Seven patients of non-osteoporotic thoracolumbar compressive fractures confirmed by plain X-ray examination and CT scanning, 14 males and 3 females, aged 35.2, all suffering from one level fracture, at T9 in 1 case, T11 in 2 cases, T12 in 7 cases, L1 in 5 cases, L2 in 1 case, and L3 in 1 case were. treated with percutaneous kyphoplasty. Under local anesthesia Kypho-X vertebra expander was inserted into the vertebral body and polymethylmethacrylate (PMMA) bone cement was filled. Then the patients were followed up for 6 months (6-24 months) by using the visual analog scale, Oswestry disability index (ODI), and the vertebra height and kyphosis were analyzed. RESULTS: All patients underwent the procedure safely. Except for two cases with complication of para-vertebra cement leakage no other complication occurred. The average surgery time was 55 min. All patients became able to get up of bed 2 days and discharged 7 days postoperatively and continued to be protected by hard prosthesis for two weeks more. The average score of VAS was 8.7 before the operation, and then gradually decreased, to 3.2 and 2.7 1 and 4 weeks postoperatively, and became 2.1 at the last follow-up (all P < 0.05). The average ODI score was 72.3 before the operation, and then gradually decreased to 48.6 and 28.9 1 week and 4 weeks postoperatively, and became 22.4 at the last follow-up (all P < 0.05). The average height of the vertebra was 14.3 mm preoperatively, and increased to 24.7 mm 1 week postoperative and 22.4 mm at the last follow up (both P < 0.05). The kyphosis of the fractured vertebra was 31.1 degrees preoperatively and decreased to 9.6 degrees 1 week postoperatively and 10.9 degrees at the last follow up (both P < 0.05). All patients returned to their previous work and life within 2 months postoperatively. CONCLUSION: Percutaneous kyphoplasty is effective and safe in the treatment of non-osteoporotic thoracolumbar compressive fractures with the advantages of minimum invasiveness, fast pain relief and recovery, as well as restoration of vertebra height and correction of kyphosis. PMID- 17288832 TI - [Traumatic responses following microendoscopic discectomy: clinical analysis of 44 patients]. AB - OBJECTIVE: To compare the traumatic responses following microendoscopic discectomy (MED) and open discectomy. METHODS: Forty-four patients with single level lumbar disk herniation underwent MED (Group A, n = 22) or open discectomy (Group B, n = 22). The intra-operational blood loss, duration of operation, intra operative blood loss, and post-operational hospital stay were noted and the pain severity of incision was evaluated by visual analog scale (VAS). Serum levels of IL-6, C-reactive protein (CRP) and creatine kinase (CK) were measured before operation and 24 h and 48 h after operation. The clinical outcomes were evaluated by Oswestry disability index (ODI) before operation and 6 months after operation. RESULTS: The intra-operative blood loss of Group A was 47.50 +/- 11.62 ml, significantly less than that of Group B (129.11 +/- 71.75 ml, P < 0.01), the duration of operation of Group A was 64.77 +/- 17.83, significantly shorter than that of Group B (78.18 +/- 24.32, P < 0.05). The postoperative hospital stay of Group A was 6.09 +/- 2.22 days, significantly shorter than that of Group B (8.73 +/- 3.53, P < 0.01). The scores of VAS 1, 2, and 3 days after the operation were all significantly lower than those of Group B (all P < 0.001). The rate of remarkable symptomatic improvement of Group A was 94.7%, not significantly different from that of Group B (94.4%, P > 0.05) The serum IL-6 showed no significant difference between these 2 groups pre-operationally, and peaked 24 h after operation and decreased 48 h after operation in both groups, returning to the pre-operational level in Group A. The IL-6 level 24 h and 48 h post operationally of Group A was 31.6 +/- 9.88 pg/ml and 26.25 +/- 9.30 pg/ml respectively, both significantly lower than those of Group B (39.16 +/- 11.14 pg/ml and 32.55 +/- 8.83 pg/ml respectively, both P < 0.05) The serum CK showed no significant difference between these 2 groups pre-operationally, and peaked 24 h after operation and decreased 48 h after operation, but still higher than those before operation, in both groups. The serum CK 24 h and 48 h after operation of Group A were 167.91 +/- 51.85 and 131.50 +/- 52.70 U/L respectively, both significantly lower than those of Group B (401.55 +/- 108.86 and 260.32 +/- 64.98 U/L, both P < 0.01). The serum CRP level showed no significant difference between these 2 groups pre-operationally, and increased post-operationally, peaked 24 h after operation and then decreased in Group A, however, continued to increase in Group B. The serum levels of CRP 24 h and 48 h post-operationally of Group A were 12.68 +/- 7.10 and 10.77 +/- 5.25 pg/ml, both significantly lower than those of Group B (20.82 +/- 8.79 and 29.95 +/- 14.85 pg/ml, both P < 0.01). The clinical outcomes 6 months after operation of these two groups were all satisfying. CONCLUSION: Both MED and open discectomy show good clinical outcomes in treatment of single level lumbar disk herniation, however, the less responses of serum IL 6, CRP, and CK show that the MED procedure is less traumatic. PMID- 17288833 TI - [Clinical research of thoracoscopy-assisted mini-open surgery for anterior column reconstruction of thoracic spine tuberculosis]. AB - OBJECTIVE: To evaluate the clinic effects of thoracoscopy-assisted mini-open surgery for anterior column reconstruction of thoracic spine tuberculosis. METHODS: Sixty patients with thoracic spine tuberculosis, involving segments T4 to T12, with a kyphotic angle of 29.2 degrees (18-42 degrees), 38 males and 22 females, aged 47.4 (19-68), with large paraspinal abscess in 50 cases, pleurisy in 17, and dural compression in 42 cases shown by imaging examination, underwent thoracoscopic-assisted mini-open surgery, including radical debridement and anterior spinal reconstruction. According to Frankel's grade, the preoperative neurological function was judged as: Grade A in 1 case, Grade B in 4, Grade C in 6, Grade D in 19, and Grade E in 30. The patients were followed up for 3.6 years. The outcomes were evaluated retrospectively. RESULTS: The operation was accomplished successfully in all 60 patients. The average operative time was 230 min (180-320 min), the average blood loss during operation was 570 ml (350-1200 ml), the mean drainage duration was 3.6 d (3-5 d). Complications occurred in 18 patients (30%). 30 patients showed neurological improvement from 1 to 3 Grades at the last follow-up. The average correction rate of kyphotic angle was 36.6%, and no obvious correction loss was detected during the follow-up. No patient showed recurrence of tuberculosis. CONCLUSION: Thoracoscopy-assisted mini-open surgery provides a simple, safe, effective, and practical technology with minimal invasiveness for the treatment of thoracic spine tuberculosis. PMID- 17288834 TI - [Therapeutic effects and complications of percutaneous anterior screw fixation for odontoid fractures]. AB - OBJECTIVE: To investigate the therapeutic effects and complications of percutaneous anterior screw fixation for odontoid fractures. METHODS: Twenty eight patients with odontoid fractures, 21 males and 7 females, aged 38.6 (21 72), 12 with type II fractures and 16 with type III fractures, including 10 cases with shallow type III fractures, according to Anderson's classification system, underwent percutaneous anterior odontoid screw fixation with one screw implant. Five to seven days after the operation the patients got out of bed to conduct dirigation. Prostheses were used for 8-12 weeks post-operationally. The patients were followed up for 43.2 months (26-62 months). Radiological examination, including X-ray and CT examinations, and clinical examinations were carried out to observe the therapeutic effects. RESULTS: Radiological examination showed bony union in 25 cases (89.3%), and non-union developed in 2 cases, 1 case was switched to posterior fusion surgery because of redisplaced fracture. The union rate was 83.3% in the type II fracture, and was 93.8% in the type III. Majority of the patients resumed an excellent cervical motion. No severe complication such as esophagus and carotid artery injury related with puncture was found. One patient had temporary superior laryngeal nerve paralysis, The screw tail was detained at the superior margin of C3 vertebral body in 5 cases, the screw penetrate the tip of odontoid process in 1 case, and the screw thread failed to pass the fracture site entirely in 1 case. CONCLUSION: An innovative alternative method with the advantages of convenient procedure, less bleeding, gentle injury for surrounding tissue, and rapid recovery, percutaneous anterior odontoid screw fixation is similarly effective as open anterior odontoid screw fixation, for the treatment of odontoid fractures. Related complication is rare and not severe. The surgery has. PMID- 17288835 TI - [Correlation of chemokines and chemokine receptors with clinical features in newly diagnosed systemic lupus erythematosus]. AB - OBJECTIVE: To explore the correlation of chemokines and chemokine receptors with clinical features of newly diagnosed systemic lupus erythematosus (SLE). METHODS: Samples of venous blood were collected from 37 newly diagnosed SLE patients, 2 males and 35 females, aged 32.5 (15-54), and 20 healthy controls. The serum concentration of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta and reduced upon activation normal T cell expressed and secreted (RANTES) were measured by ELISA. Samples of anticoagulative serum were collected from 18 of the 37 newly diagnosed SLE patients and 10 healthy controls. The expression rates of CCR1, CCR3, and CCR5 on CD4+ T cells were detected by flow cytometry. Indirect immunofluorescence method was used to detect the anti-ds-DNA antibody, and blot immunoassay was used to detect the anti-RNP and anti-SSA antibodies. The associations of chemokines and chemokine receptors with the clinical features were analyzed. RESULTS: The serum concentration of MIP-1alpha of the SLE patients was (37 +/- 25) ng/L, significantly higher than that of the controls (8 +/- 9) ng/L (P < 0.001). The serum concentration of MIP-1beta of the SLE patients was (160 +/- 140) ng/L, significantly higher than that of the controls (76 +/- 41) ng/L (P = 0.003). The serum concentration of RANTES of the SLE patients was (184 +/- 22) ng/L, not significantly different from that of the controls (144 +/- 79) ng/L (P > 0.05). The serum concentration of MIP-1alpha of the SLE patients with fever was 52 ng/L +/- 27 ng/L, significantly higher than that of the SLE patients without fever (28 ng/L +/- 19 ng/L, P = 0.006). The serum concentration of MIP 1beta of the SLE patients with arthritis was 221 ng/L +/- 158 ng/L, significantly higher than that of the SLE patients without arthritis (95 ng/L +/- 83 ng/L, P = 0.008). The serum concentration of RANTES of the SLE patients with low blood platelet count was 130 ng/L +/- 122 ng/L, significantly lower than that of the SLE patients with normal blood platelet count (212 ng/L +/- 114 ng/L, P = 0.049). The percentage of CD4+ CCR3+ T cell subgroup in CD4+ T cell in peripheral blood of the SLE patients positive in anti-RNP antibody was 14.8% +/- 3.0%, significantly lower than that of the SLE patients negative in anti-RNP antibody (11.3% +/- 2.6%, P = 0.018). CONCLUSION: Abnormality of different chemokines and chemokine receptors may concern with different clinical features of SLE. PMID- 17288836 TI - [Inhibition of cartilage destruction in collagen-induced arthritis by altered CII 263-272 peptide: experiment with rats]. AB - OBJECTIVE: To study the inhibitory effect of altered collagen II (CII) 263-272 peptide (sub268-270) with three consecutive substitutions of TCR-contacting residues on joint inflammation and cartilage destruction in collagen-induced arthritis (CIA). METHODS: Thirty-two Lewis rats were injected intracutaneously with bovine collagen type II so as to establish models of arthritis and then were randomly divided into 4 equal groups to be injected intravenously with sub268-270 30 microg, 5 microg, or 1 microg and PBS twice a week for 3 weeks. The therapeutic effect of the altered peptide on arthritis was evaluated by arthritis score. After the treatment the rats were killed and their ankle joints were taken to undergo pathological examination to observe the existence of synovitis, pannus formation, cartilage damage, and bone erosion. Blood samples were collected to detect the serum cartilage oligomeric matrix protein (COMP). Cartilage proteoglycan-specific dye safranin O was used on the joint sections to observe the coloration of the dye in the cartilage. RESULTS: The arthritis score in rats treated by 30 microg altered CII peptide was (5.6 +/- 2.63), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(9.67 +/- 5.61), (10.02 +/- 5.06), and (11.8 +/- 5.34) respectively, all P < 0.01]. The synovitis score of the 30 microg group was (1.11 +/- 0.43), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.87 +/- 0.78), (2.11 +/- 0.83), and (2.25 +/- 0.73) respectively, all P < 0.01]. The pannus score of the 30 microg group was (1.11 +/- 0.43), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.83 +/- 0.79), (2.07 +/- 0.91), and (2.27 +/- 0.71) respectively, all P < 0.01]. The cartilage damage score of the 30 microg group was 0.56 +/- 0.23), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.91 +/- 0.83), (2.13 +/- 0.79), and (2.29 +/- 0.69) respectively, all P < 0.01]. The bone erosion score of the 30 microg group was (0.53 +/- 0.21), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.71 +/- 0.67), (1.88 +/- 0.93), and (2.01 +/- 0.93) respectively, all P < 0.01]. The serum COMP of the 30 microg group was (2.21 +/- 0.76), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(5.63 +/- 1.73), (6.04 +/- 1.76), and (7.00 +/- 1.46) respectively, all P < 0.01]. The content of safranin O (A value) in the joint section of the 30 microg group was (2.35 +/- 0.76), significantly higher than those of the 5 microg, 1 microg, and blank control groups [(1.57 +/- 0.63), (1.37 +/- 0.53), and (1.00 +/- 0.41) respectively, all P < 0.01]. CONCLUSION: The altered CII peptide sub268-270 effectively ameliorates CIA and inhibits the cartilage damage in CIA, and may modify the disease course of rheumatoid arthritis. PMID- 17288837 TI - [Correlation between an insertion-deletion polymorphism in the pepsinogen C gene and gastric cancer as well as its precursors]. AB - OBJECTIVE: To assess the relationship between the insert-deletion polymorphism in the Human pepsinogen (PGC) gene and susceptibility to gastric cancer, together with its precursors, and to investigate the interaction between PGC polymorphism and H. pylori infection in the development of gastric cancer. METHODS: PGC gene polymorphism in 141 patients with gastric cancer and 564 matched non-cancer controls were detected by polymerase chain reaction (PCR), and the relation between the PGC polymorphism and gastric cancer was examined. Serum H. pylori-IgG was determined with ELISA method. The odds ratios and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression model. The effect-modified model was used to evaluate the PGC-H. pylori interaction. RESULTS: No significant association between the frequency of homogenous allele 1 of PGC gene and the sex and age of the subjects was observed. The subjects with the homogenous allele 1 had an increased risk of developing atrophic gastritis (OR: 3.103, 95% CI: 1.440-6.686), and gastric cancer (OR: 2.962, 95% CI: 1.370 6.404), and Intestinal metaplasia (OR: 1.659, 95% CI: 0.998-2.757) comparing with those with the non-homogenous allele 1. For subjects carrying both homogenous allele 1 and H. pylori-IgG positive, there was an significant increased risk of developing atrophic gastritis and gastric cancer (likelihood test ratio test: P = 0.023, P = 0.005). CONCLUSION: PGC gene polymorphism may be associated with susceptibility to gastric cancer and atrophic gastritis. The PGC gene polymorphism and H. pylori infection seem to display an interaction in the development of gastric cancer. PMID- 17288838 TI - [Imatinib mesylate in the treatment of advanced gastrointestinal stromal tumors]. AB - OBJECTIVE: To evaluate the efficacy and safety of imatinib mesylate in the treatment of patients as preoperative supplement, or used alone for unresectable and/or metastatic gastrointestinal stromal tumors (GIST). METHODS: A total of 51 cases with advanced GIST were proved pathologically. Among them, CD117 was detected positive in 47 patients and negative in 4 patients; 4 patients received imatinib mesylate before operation and 47 patients with unresectable and (or) metastatic GIST received oral imatinib mesylate daily at dose of 300-800 mg. One patient was lost in follow-up and the objective effect was evaluated in 50 patients. RESULTS: 3 of the 50 patients (6.0%) achieved complete response (CR), 34 (68%) had partial response (PR), 5 (10.0%) had stable disease (SD) and 8 (20.0%) had progression disease (PD). The median time to progression (mTTP) was 16 months during which most of the patients experienced benefit. 32 patients had been followed up for more then 1 year. The 1-year and 2-year survival rate were 95.3%, 89% respectively. 50 patients were valuable for the toxicity assessment according to the WHO standard. The main toxicity included grade I-II edema of periorbital area and lower limb in 72.0% (36/50) patients, leukopenia was present in 46% (23/50) and intratumoral bleeding in 4.0% (2/50). Other toxicities included mild fatigue (28.0%), abdominal pain (14.0%), efflorescence (18.0%), nausea and vomiting (18.0%). CONCLUSIONS: As an inhibitor of tyrosine kinase, imatinib mesylate is generally well tolerated and has been proved to be effective and safe during prolonged treatment of patients with advanced gastrointestinal stromal tumors. Its toxicity is acceptable. PMID- 17288839 TI - [Clinicopathological features and surgical treatment of familial adenomatous polyposis]. AB - OBJECTIVE: To investigate the clinicopathological features and surgical treatment of familial adenomatous polyposis (FAP). METHODS: The clinical data of 51 patients with FAP, 29 males and 22 females, aged 36.6 (17-67), hospitalized Sep 1980-Dec 2005 were analyzed. RESULTS: Twenty-nine patients had family history of FAP and 7 of them were discovered during screened because of family history. The main clinical manifestations included rectal bleeding or bloody stool, diarrhea, abdominal pain, and general discomfort in the abdomen. Synchronous malignant changes were found in 28 patients while hospitalized. The incidence of colorectal cancer was 54.9%. The average age of those with colorectal cancer was 40.5 and the age of those without colorectal cancer was 31.9. 81.8% of the colorectal cancers occurred on the rectum and sigmoid colon. Different types of proctocolectomy were performed on 50 patients, and one patient received only pelvic radiotherapy. The follow-up rate was 74.5%. Only 27.5% of the patients received regular surveillance. Colorectal cancer was found in 8 patients after the first operation. So far 17 patients died. CONCLUSIONS: There were no specific clinical manifestations for FAP. Colonoscopy is the most important diagnostic procedure. Surgical treatment should be given as soon as possible. The specific operation type should be based on the individual aspects of patients. Life-time surveillance and follow-up are very important. PMID- 17288840 TI - [Neural apoptosis and apoptosis-related genes in intracerebral hemorrhage patients]. AB - OBJECTIVE: To observe the neural apoptosis and expression of apoptosis-related genes in brain in order to elucidate the regulation mechanism in the perihematomal region of intracerebral hemorrhage (ICH) patients. METHODS: Specimens of perihematomal region in human brain were obtained from 29 patients undergoing surgical evacuation of an intracerebral hematoma. Specimens of brain tissue were collected from the corpses of 6 persons within 3 hours after the accidental death. Neural apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5' triphosphate nick end labeling (TUNEL) method and immunohistochemistry was used to detect the expression of Bcl-2, Bax, P53, and caspase-3 genes. RESULTS: The apoptosis rates of the ICH group was 4.10 +/- 0.28, significantly higher than that of the control group (0.57 +/- 0.43, P < 0.01). The expression rate of Bcl-2 the ICH group was 2.68 +/- 0.52, significantly higher than that of the control group (1.54 +/- 0.56, P < 0.01). The expression rate of Bax of the ICH group was 3.49 +/- 0.18, significantly higher than that of the control group (0.96 +/- 0.27, P < 0.01). The expression of P53 was 4.12 +/- 0.63, significantly higher than that of the control group (0.96 +/- 0.71, P < 0.01). The expression of caspase-3 of the ICH group was 3.50 +/- 0.25, significantly higher than that of the control group (0.74 +/- 0.73, P < 0.01). The expression levels of Bcl-2 and P53 were negatively correlated with the apoptosis rate (both P < 0.01), while the expression levels of Bax and caspase-3, and the Bax/Bcl-2 ratio were positively correlated with the apoptosis rate in perihematomal region of ICH patients (all P < 0.01). CONCLUSION: Apoptosis is involved in the delayed brain injury after ICH in human and is the main factor of delayed neural death. Some of the genes take part in the regulation of neural apoptosis: Bax and caspase-3 hasten the apoptosis while Bcl-2 and P53 restrain it. PMID- 17288841 TI - [Regional specificity in proliferation capacity of neural stem cells from hippocampus and epithalamus: study with rats]. AB - OBJECTIVE: To compare the regional specificity in proliferation capacity of neural stem cells derived from hippocampus and epithalamus: study with rats. METHODS: Neural stem cells (NSCs) were separated mechanically from the hippocampus and the epithalamus of an embryo of SD rat respectively and cultured in serum-free medium to observe the growth status dynamically and their in vitro growth curves were drawn. Single cell clones were established and identified by immunofluorescence staining. The surface morphology of the clone balls were observed by using scanning electron microscope. The ultrastructure was observed by scanning electron microscopy. The 3D morphology was observed under a laser confocal microscope. NSCs were co-incubated with 5-bromodeoxyuridine (Brdu) and immunofluorescence staining was used to observe their in vitro proliferation potentials. Studies on. RESULTS: The in vitro growth of the hippocampus-derived NSCs was basically the same as that of the epithalamus-derived NSCs, however, the culture fluid of the epithalamus-derived NSCs became yellowish 18 hours after the inoculation, significantly earlier than that of the hippocampus-derived NSCs. Showing a faster multiplication rate of the latter. Scanning electron microscopy showed that these two types of NSCs had a similar ultrastructural feature. Phase contrast microscopy and laser confocal microscopy showed similar form in the NSCs from two different sources. Co-incubation with found that the Brdu positive rate of the epithalamus-derived NSCs was 74.87%, significantly higher than that of the hippocampus-derived NSCs (63.07%, P < 0.05). The cell growth curves of the NSCs from both sources displayed the same multiplication trend, however, the NSC count of the epithalamus-derived NSCs at the 8th, 12th, 16th, 20th, and 24th days after culture were all higher than those of the corresponding hippocampus-derived NSCs at the same time-points (all P < 0.05). CONCLUSION: Both embryonic hippocampus derived and epithalamus-derived NSCs can be acquired by using mechanical separation and serum-free culture method. The two types of cells have a similar morphological structure and possess the in vitro multiplication capacity. However, the multiplication rate of the epithalamus-derived NSCs is higher than that of the hippocampus-derived NSCs. PMID- 17288842 TI - [Effects of benzo(a)pyrene on the expression of gamma-glutamate-cysteine ligase: a primary study with rat alveolar epithelial cells]. AB - OBJECTIVE: To study the effect of benzo(a)pyrene [B(a)P] on the expression of gamma-glutamate-cysteine ligase (gamma-GCS) in rat alveolar epithelium cells (CCL 149 cell line). METHODS: Rat alveolar cells of the line CCL-149 were cultured and exposed to B(a)P of the concentrations of 0, 100, 500, and 5000 microg/L respectively for 24, 36, 48, and 72 hours respectively. Then the A values was measured to observe the influence of B(a)P on the growth of the CCL-149 cells. Another CCL-149 cells were exposed to B(a)P of the concentration of 200 microg/L for 6 h, then the nuclear protein was extracted. Electrophoretic mobility shift assays (EMSA) and antibody supershift assay were used to observe the specific binding of aryl hydrocarbon receptor nuclear translocator (ARNT) to the E-box element. CCL-149 cells were cultured to 95% confluent and transfected with GCLC luc and GCLC-delE-box-luc for 6 h, exposed to B(a)P of different concentrations (2, 20, and 200 microg/L) for 2, 6, 12, or 24 h, then the cells were harvested and the luciferase activity was measured. Cells treated with DMSO were used as negative control group. RESULTS: B(a)P of the concentrations over 5000 microg/L significantly influenced the growth of the CCL-149 cells (all P < 0.01). Treated with B(a)P induced binding of AHR/ARNT to E-box element was significantly increased by treatment of B(a)P. Treatment of B(a)P of different concentrations at different time points did not significantly influence the luciferase activity (all P > 0.05). CONCLUSION: B(a)P induces the binding of ARNT to the E-box element on the gamma-GCS gene, but this interaction between E-box and ARNT seems not to have effect on the gene expression of gamma-GCS. PMID- 17288843 TI - [Influence of various ventilation manier on rat's lung and the expression of lung endotoxin receptor CD14 mRNA]. AB - OBJECTIVE: To observe the influence of mechanical ventilation (MV) on rat's lung and the expression changes of lung endotoxin receptor CD14 mRNA. METHODS: Forty eight male SD rats weighing 330-360 g were randomly divided into 4 groups (n = 12 each): group R received no mechanical ventilation, group P received small MV (VT = 6 ml/kg, PEEP = 8 mm Hg), group M received conventional MV (VT = 12 ml/kg, PEEP = 0 mm Hg), and group N received large tidal volume mechanical ventilation (VT = 40 ml/kg, PEEP = 0 mm Hg). The animals were anesthetized with intraperitoneal pentobarbital 100 mg x kg(-1), tracheotomized and mechanically ventilated (I:E = 1:1, FiO2 = 21%). The respiratory rate (RR) of MV was adjusted to maintain the end-tidal carbon dioxide in the rang of 35-45 mm Hg throughout the procedure. Right carotid artery and left femoral vein were cannulated for BP monitoring and fluid and drug administration. 6 rats in each group were injected 50 mg/kg Evans Blue (EB). The experiment was culminated in 3 hours, then the rats were killed by exsanguination via arteria carotis interna. Morphologic change scores of the rats' lungs, wet/dry weight ratio of lung tissue (W/D), bronchial lavage fluid (BALF) inflammatory cell population, and permeability of vessel wall were evaluated. The concentration of TNF-alpha and MIP-2 in the plasma were determined by enzyme immunoassay method (ELISA). The expressions of lung tissue endotoxin receptor CD14 were detected by RT-PCR, macrophage CD14 in BALF was also detected by immunohistochemistry. RESULTS: pulmonary pathomorphology scores: there were no alteration in R group and P group, but it were slightly increased in M group, there was significantly elevated in N group as compare to M group (F = 8.0, P = 0.000). Pulmonary tissue wet/dry weight ratio (W/D): Compare with R group, There was no statistically significant difference in P group and M group; the elevation in N group (t = 4.103, P = 0.02), EB: Compare with R group, There was no statistically significant difference in P group and M group; the obviously elevation in N group (t = 36.634, P = 0.000). WBC in BALF: Compare with R group, there was no change in P group, the elevation in M group (t = 4.272, P = 0.02), there was significantly elevated in N group (F = 26.68, P = 0.000). TNF-alpha had no manifest variation in 4 groups. MIP-2: compare with R group (31.5 +/- 2.4), There was no statistically significant difference in P group (35.4 +/- 5.3), the elevation in M group (44.7 +/- 6.9, t = 7.85, P = 0.04), there was significantly elevated in N group (167.7 +/- 11.8, t = 27.779, P = 0.000). The expressions of macrophage CD14 protein in BALF and lung tissue CD14 mRNA were fundamentally coincident in R group and P group; the expressions of CD14 mRNA were elevated, but the expressions of CD14 protein were no change in M group; the expressions of CD14 in N group manifestly elevated (P = 0.000). CONCLUSIONS: Conventional MV induces minor injury in rat's lung and can up regulate the expression of CD14 mRNA in the lung, but not up regulate the expression of CD14 protein; large tidal volume MV induces injury of rat's lung and evidently up regulates CD14 expression in the lung. Protective MV can avoid the above mentioned variations in rat's lung. PMID- 17288847 TI - Revolution next--the multidetector CT. PMID- 17288848 TI - Inhibition of tryptophan pyrrolase activity in restraint female rats following medroxyprogesterone administration. AB - OBJECTIVE: To determine the effects of Medroxyprogesterone (hormonal contraceptive) in restraint stressed female rats in relation to tryptophan metabolism. DESIGN: Pre-clinical study. PLACE AND DURATION OF STUDY: Department of Biochemistry, University of Karachi. The investigation was carried out in the year 2003. MATERIALS AND METHODS: Female Albino Wistar rats (150-200 gm body wt) were selected and divided into four groups (n=5 in each group). Rats were injected intraperitoneally either vehicle or Medroxyprogesterone (25mg/kg/ml) and were immediately subjected to 2 hours restraint stress while respective controls remained in their home cages. RESULTS: In restraint stress group, hepatic holo and total tryptophan pyrrolase activities were increased. Liver tryptophan, total serum tryptophan and albumin concentration were decreased. Brain tryptophan, 5HT and 5HIAA concentrations were increased. Medroxyprogesterone administration in unrestraint rats inhibited holo, total and apo enzyme activities with increases in liver tryptophan concentrations. Effect of restraint stress following Medroxyprogesterone administration when compared with drug injected unrestrained group showed increase in holo and total tryptophan pyrrolase activities with decrease in liver tryptophan concentrations. Brain tryptophan, 5HT and 5HIAA levels were increased. Results when compared with vehicle injected stressed-rats showed that total and apo tryptophan pyrrolase activities were decreased. Liver tryptophan, serum tryptophan and albumin concentrations were increased but brain tryptophan metabolism was not effected. CONCLUSION: It is concluded that Medroxyprogesterone inhibits stress induce increases in peripheral tryptophan metabolism and increases plasma tryptophan. Although stress induced increases in brain indoles were not effected by the drug at two hours, further studies on time course effects of this drug will be needed to explore its possible anxiolytic effects. PMID- 17288849 TI - Comparison of heart rate and QTc duration in patients of cirrhosis of liver with non-cirrhotic controls. AB - OBJECTIVE: To compare QTc duration and Heart Rate (HR) in patients with cirrhosis with non-cirrhotic controls. DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Civil Hospital and Lyari General Hospital, Karachi, from March 2004 to February 2006. PATIENTS AND METHODS: Confirmed patients of cirrhosis were selected and allocated to Group-I. An equal number of non-cirrhotic patients were taken as control and were allocated to Group-II. ECG was recorded and values of HR and QTc were calculated. Comparison of increased frequency of HR and prolongation of QTc were done using Chi-square test or Fisher's Exact Test with significance level at /= 3.00 on routine HIV Ab testing were 100.0% positive by WB and/or repeatedly reactive by the second test. In samples with a S/CO ratio < 3.00, 11.1% were positive by WB and/or the majority were nonreactive by the second test. Among HIV-infected donors, 89.5% possessed risk factors (which had been denied previously), 56.5% were repeatedly reactive by other screening procedures and 88.6% were coinfected with other blood-transmissible viruses. CONCLUSIONS: When the EIA S/CO ratio is >/= 3.00, WB can be replaced by a second screening test. The pre-donation questionnaire should be improved to detect risk behavior in prospective donors. There was a high association between HIV and other blood transmissible viruses. PMID- 17288906 TI - Factors associated with reported hepatitis C and HIV among injecting drug users in ten European cities. AB - BACKGROUND: To analyze self-reported prevalence of HCV and HIV in a sample of socially excluded injecting drug users, as well as factors associated with the presence of these diseases. METHODS: Cross-sectional study. Data were collected with a structured, face-to-face questionnaire by outreach workers and privileged access interviewers in 1131 participants who had injected heroin and/or cocaine over the past year (71.5% men; mean age, 30 years) from Seville and Granada, Spain; Cologne, Germany; Vienna, Austria; Brussels, Belgium; Athens, Greece; Dublin, Ireland; London, England; Lisbon, Portugal and Perugia, Italy. RESULTS: Among the total sample, 595 (52.6%) participants reported HCV-positive status and 143 (12.6%) HIV-positive status. Multivariate analysis for HCV showed that women are at less risk than men, and that longer drug use, injecting while in prison, sharing needles, and reported positive status for tuberculosis, HBV, HIV or sexually-transmitted disease are positively associated with HCV. Participants reporting positive HIV status were generally older, had injected drugs while in prison, had completed less than 8 years of schooling, were divorced, had no regular employment, and declared infection with tuberculosis, sexually transmitted disease and HCV. CONCLUSIONS: The highest incidences of HCV and HIV were reported by participants in a poorer social and health situation. Drug addicts must cope not only with their addiction but also with the process of social exclusion they are immersed in. To the greatest extent possible, any course of action for this group should be built into integrated, coordinated plans that take a broad approach to the main issues involved. PMID- 17288907 TI - [Cost of nucleoside analogue reverse transcriptase inhibitor-related toxicity in HIV-1-infected patients]. AB - OBJECTIVE: To estimate the impact of toxicity related to nucleoside analogue reverse transcriptase inhibitors (NRTI) on the total cost of medical care in HIV 1-infected patients. METHODS: . A pharmacoeconomic model was developed from the data obtained by a prospective, observational, multicenter study performed in Spain (Recover). The study patients had developed one NRTI-associated adverse event (AE) that justified discontinuation of treatment with the drug. All costs derived from NRTI-associated AEs in the HAART regimens of HIV-1-infected patients over a period of one year were assessed. The cost assessment (2005 values) included direct medical costs (drugs and AE management) and indirect costs (loss of productivity). The healthcare resources used in AE management were estimated by an expert panel of clinicians. RESULTS: The use and cost of resources rose with increasing severity of all the AE. The average total cost per patient was estimated to be 4012 euro, which included 1789 euro in drug costs (NRTI associated with therapy discontinuation due to AE), and 2223 euro in direct and indirect costs of AE management (45% and 55% of total cost, respectively). Seventy-three per cent of AE-associated costs per patient came from lipoatrophy (560 euro), lipodystropy (535 euro) and peripheral neuropathy (533 euro). CONCLUSION: Management of NRTI-related toxicities is more costly than NRTI acquisition and produces a significant increase in the overall healthcare expenditure for HIV-1-infected patients. This fact should be taken into account when designing the most efficient antiretroviral treatment strategies. PMID- 17288909 TI - [Guidelines for the diagnosis and treatment of patients with bacteriemia. Guidelines of the Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica]. AB - Bacteremia is a complex clinical syndrome in constant transformation that is an important, growing cause of morbidity and mortality. Even though there is a great deal of specific information about bacteremia, few comprehensive reviews integrate this information with a practical AIM. The main objective of these Guidelines, which target hospital physicians, is to improve the clinical care provided to patients with bacteremia by integrating blood culture results with clinical data, and optimizing the use of diagnostic procedures and antimicrobial testing. The document is structured into sections that cover the epidemiology and etiology of bacteremia, stratified according to the various patient populations, and the diagnostic work-up, therapy, and follow-up of patients with bacteremia. Diagnostic and therapeutic decisions are presented as recommendations based on the grade of available scientific evidence. PMID- 17288908 TI - [Age distribution of serological profiles of Epstein-Barr virus infection: review of results from a diagnostic laboratory]. AB - INTRODUCTION: The objective of this study was to examine the distribution of serological profiles of Epstein-Barr virus (EBV) infection according to age. METHODS: We retrospectively review EBV specific antibody determinations performed at our hospital between 2003 and 2004. RESULTS: The distribution of acute EBV infection by age showed a bimodal pattern, with peaks at the age of 2-4 years and 14-18 years. Among the 21-30 year-old age group, there was a higher percentage of seronegative men than women. Seroprevalence in patients aged 31 years or more was 99%. CONCLUSIONS: Most primary EBV infections occur in early childhood or adolescence. The increase in seroprevalence takes place at an earlier age in females than in males. EBV seroprevalence in adult patients is very high. PMID- 17288910 TI - [Spanish recommendations for proper use of enfuvirtide]. AB - Enfuvirtide is a high-cost, parenterally administered drug commonly used in late phases of HIV infection, when its efficacy may be compromised. To optimize enfuvirtide use, consensus recommendations for this purpose have been formulated by 247 physicians attending patients with HIV infection in Spain. A literature review was performed in which grades of evidence and recommendations were defined according to the origin of the data (randomized clinical trials, non-randomized studies, expert opinion). Twenty-eight local consensus meetings were held between May and September 2005 to discuss the most important aspects related to the use of enfuvirtide, following a pre-established system used in all the meetings. The main conclusions were as follows: a) enfuvirtide use is often excessively delayed and is given to patients with little chance of treatment success; b) enfuvirtide is indicated in patients who require antiretroviral treatment and for whom an optimum treatment with three other fully effective drugs cannot be designed; c) the most important prognostic factor is the availability of at least one other completely active drug; d) there is no infallible method to avoid the development of local reactions, but measures are available to decrease their incidence and severity; and e) patient counseling and training for correct administration of the drug are essential to improve adherence, the repercussions of local reactions and, of course, the efficacy of the treatment. PMID- 17288911 TI - [Immunosuppression and infection in transplant recipients]. AB - Recognizing a foreign element is an inherent characteristic of living beings and guarantees their survival. Evading this defense mechanism is one of the most difficult requirements for transplant success, but it leads to a series of consequences, mainly related to infection. T lymphocytes are the cornerstone of the allogenic response. These cells recognize intracellular and extracellular antigens over HLA molecules in host cells. As a consequence, lymphocytic expansion occurring on several levels is produced, and a humoral or cellular response is the final result. The immunosuppression regimens used in transplantation include induction, maintenance and rescue therapy. Induction therapy serves primarily to decrease the proportion of T-cell precursors and to lower the efficacy of antigen presentation. With respect to maintenance therapy, cyclosporine and tacrolimus inhibit cytokine transcription, azathioprine, and mycophenolate mofetil inhibit nucleotide synthesis, and sirolimus and everolimus inhibit transduction of growth factor signals. As a consequence of immunosuppression, opportunistic microorganisms may appear with endogenic reactivation of latent infection or from an exogenous origin. Prevention of these infections by proper knowledge of the risk factors, rapid diagnosis, and adequate management are fundamental to guarantee the survival of the patient. PMID- 17288912 TI - [A 31-year-old woman with a mass in the thigh muscle]. PMID- 17288913 TI - [Cervical lymphadenitis, pancytopenia and fever in a patient with HIV infection]. PMID- 17288914 TI - [Cervical lymphadenitis due to Mycobacterium avium in an immunocompetent adult]. PMID- 17288915 TI - [Evolution of HIV resistance mutations in the Valme referral center]. PMID- 17288917 TI - [Mitral endocarditis due to Escherichia coli]. PMID- 17288916 TI - [Escherichia coli endocarditis: a report of two cases]. PMID- 17288918 TI - [Spontaneous pneumococcal peritonitis in a patient with an intrauterine device]. PMID- 17288919 TI - [Pneumococcal meningitis following spinal anesthesia]. PMID- 17288920 TI - [Gender differences in early reperfusion treatment after myocardial infarction]. AB - BACKGROUND AND OBJECTIVE: Clinical variability in myocardial infarction (MI) regarding age, comorbidities and atypical symptoms could determine gender differences in inhospital care. This study analyzes the magnitude and determinants of differences between men and women in early reperfusion therapy in people hospitalized after MI. PATIENTS AND METHOD: 2,836 patients who arrived to hospital with MI were studied (IBERICA-Basque Country study). The relative risk (RR) of receiving early reperfusion for men versus women, adjusted by age, clinical characteristics, risk factors, and pre-hospital delay was estimated. The effect decomposition methodology and the log binomial regression were applied. RESULTS: 29% of patients were women with a median age of 77 years. The RR of revascularization in men compared to women was different according to age. When factors such as hypertension diabetes, Killip III-IV at admission and atypical symptoms were taken into account, statistically significant differences between sexes were not detected at 45 years old (RR=0.91; 95% CI=0.77-1.07). However, for 64 years old and over, the RR of reperfusion was 1.24 (95% CI=1.05-1.47). Both the differences by sex and the sex-age interaction were no longer statistically significant after adjusting by pre-hospital delay. CONCLUSIONS: The delay to receive medical care in elderly women is responsible of gender differences in early reperfusion. It is necessary to analyze the reasons for treatment-seeking delay. PMID- 17288921 TI - [Cardiovascular risk profile of uncontrolled hypertensive patients. The Control Project study]. AB - BACKGROUND AND OBJECTIVE: To assess absolute cardiovascular risk and co morbidities in uncontrolled hypertensive patients (blood pressure [BP]>or=140/90 mmHg or>or=130/80 mmHg in diabetics) attending Primary Care Physicians in Spain, and to determine the attitudes of these physicians towards this problem. PATIENTS AND METHOD: Cross-sectional, multicenter study involving 356 general practitioners around Spain. Absolute cardiovascular risk was assessed according to ESH-ESC 2003 Guidelines in a sample of 1,710 patients. RESULTS: Two hundred ninety seven patients were excluded by several reasons and a total of 1,413 hypertensive patients were valuable (mean age: 65.3+/-11.4 years; 56.7% women). Normal BP values (<140/90 mmHg) were exhibited by 0.2%, high-normal BP (120 139/80-89 mmHg) were exhibited by 2.8%, grade 1 hypertension (140-159/90-99 mmHg) by 49.9%, grade 2 hypertension (160-179/100-109 mmHg) by 39.3%, and grade 3 hypertension (>or=180/110 mmHg) by 7.9%. Associated cardiovascular risk factors were observed in 96.0% of patients (95% CI=94.7-97.2%), target organ damage in 34.5% (95% CI=31.6-36.5%), and cardiovascular clinical disease in 36.0% (95% CI=33.5-38.5%). According to ESH-ESC 2003 Guidelines 34.0% (CI=31.5-38.2%) were at very-high risk; 29.4% (95% CI=26.4-32.8%) at high risk; 30.4% (95% CI=27.2 33.7%) at moderate risk and 5.4% (95% CI=3.9-7.2%) at low risk of cardiovascular disease. Despite the high absolute risk, physicians did not do any therapeutic change in 30.4% (95% CI=28.2-33.5%) of uncontrolled hypertensive patients. Most of them (64.26%) considered that bad compliance to life style changes was the reason for inadequate BP control. The most frequent measure introduced was the association of additional drugs. CONCLUSIONS: Absolute cardiovascular risk in uncontrolled hypertensive patients attending Primary Care Physicians in Spain is very relevant. Sixty-five percent of these patients are at high or very high risk with a high prevalence of target organ damage or associated cardiovascular clinical disease. Therapeutic attitudes towards these patients are still very conservative although they are improving compared with previous studies. PMID- 17288922 TI - [Ankle-brachial index to detect peripheral arterial disease: concordance and validation study between Doppler and an oscillometric device]. AB - BACKGROUND AND OBJECTIVE: To evaluate the sensitivity and specificity of ankle brachial index (ABI) determined by oscillometry, using a Doppler ultrasound probe as a gold standard. We also aimed to evaluate the agreement between both methods. PATIENTS AND METHOD: Right and left ABI measurements (ABIr,ABIl) with oscillometric (OMRON-705-CP) and Doppler (DIADOP-50) devices in hypertensive patients without peripheral arterial disease. RESULTS: One hundred patients, 61 women, 66.4 (SD 10.9) year-old, smokers 16%, diabetics 38%. Oscillometric and doppler ABI could be calculated in 83% and 93% of patients, respectively. Oscillometric ABIr and ABIl measurements were <0.9 in 9.6% (CI 95%, 4.2-18.1) and 8.4% (CI 95%, 3.4-16.6), respectively, and Doppler measurements were 10.8% (CI 95%, 5.3-18.9) and 15.4% (CI 95%, 8.7-24.5) respectively. The oscillometric ABIr and ABIl sensitivity was 37.5% (CI 95%, 13.7-69.4) and 20.0% (CI 95%, 5.7-51.0) respectively, and the specificity was 93.0% (CI 95%, 84.6-97.8) and 97.1% (CI 95%, 89.9-99.2), respectively. The intraclass correlation (index Doppler/oscillometric device) was 0.64 (CI 95%, 0.44-0.77) for ABIr and 0.62 (CI 95%, 0.41-0.76) for ABIl. CONCLUSIONS: About 8.4-15.4% of hypertensive patients attended have an abnormal Doppler ABI measurement. There is not a good concordance between Doppler and oscillometric ABI measurements. This oscillometric device does not seem useful as an ABI screening method. PMID- 17288923 TI - [What to do to improve the survival of patients with systemic lupus erythematosus?]. PMID- 17288924 TI - [Female vulnerability in myocardial infarction]. PMID- 17288925 TI - [Guidelines for the development and evolution of therapeutic guides: recommendations for design and elaboration]. PMID- 17288926 TI - [A 73-year-old male with protracted fever and alteration of hepatic parameters]. PMID- 17288927 TI - [Seroprevalence of antibodies against Chlamydophila pneumoniae in the adult population of Lanzarote Island, Spain]. PMID- 17288928 TI - [The autonomy principle and the advance directives]. PMID- 17288929 TI - [Acute disseminated encephalomyelitis associated to overdose of cocaine]. PMID- 17288930 TI - [Diagnosis: pericardial fat necrosis]. PMID- 17288931 TI - [Effectivity of thalidomide and dexamethasone for the treatment of refractory multiple myeloma: a retrospective study of 36 consecutive cases]. AB - BACKGROUND AND OBJECTIVE: Multiple myeloma (MM) is a plasm-cell neoplasm characterized by a monoclonal protein in the serum or urine. Thalidomide is effective as second line treatment. PATIENTS AND METHOD: We performed a retrospective study of 36 consecutive patients with refractory MM treated with thalidomide and dexamethasone as second line therapy, with the objective of analyzing the rate of response (primary end point), progression-free survival (PFS) and toxicity profiles (second end points). RESULTS: In our study the overall response rate was 55.6%, with a median of PFS of 12.6 months (95% confidence interval: 4-21 months). PFS at 6, 12 and 18 months was 61.11%, 50% and 22.22% respectively. 30.6% of the patients had neuropathy, 11.11% had rash and 5.55% had deep vein thrombosis. CONCLUSIONS: The combination of thalidomide and dexamethasone is an effective and safe second line treatment for refractory MM, with a manageable toxicity. PMID- 17288932 TI - [Treatment of atrial fibrillation at different levels of health care]. AB - BACKGROUND AND OBJECTIVE: Atrial fibrillation is managed in multiple settings by different specialists. We sought to analyze treatment and compliance of the prevailing guidelines of patients with atrial fibrillation attended at different levels of health care and to quantify interventions to correct treatment inadequacies. PATIENTS AND METHOD: We included all adult patients with atrial fibrillation who presented during a 14 day-period to different levels of health care of a tertiary hospital and a related primary care clinic (family physician, cardiologist, emergency department, hospitalization). In all of them, clinical and epidemiological data in relation to atrial fibrillation, and all data referring to treatment and compliance of guidelines, were recorded prospectively. RESULTS: 293 patients were included. Clinical and epidemiological data were similar in the different settings. A great diversity in atrial fibrillation treatment was observed. In 30 and 33% of the patients, antiarrhythmic and antithrombotic treatment, respectively, did not meet the recommendations of the prevailing guidelines. The adequacy was inferior in primary care. The adequacy percentages increased slightly after the medical attention (2 and 3% respectively, p non significant) with no differences in this increase between the different settings. CONCLUSIONS: There are no epidemiological differences between patients with atrial fibrillation treated at different levels of health care. An important number of patients do not follow the recommendations of the prevailing guidelines. There is a clear medical abstention in incorrectly treated cases. PMID- 17288933 TI - [Incidence of pneumonia in HIV-infected patients in the highly active antiretroviral therapy era]. AB - BACKGROUND AND OBJECTIVE: There is scant data comparing the incidence of pneumonia in the community and in the human immunodeficiency virus (HIV) population in highly active antiretroviral therapy (HAART) era. PATIENTS AND METHOD: Prospective study during 18 months. Data were obtained by the means of the electronic clinical record. Incidence rate was compared between HIV positive and negative patients. RESULTS: There were 529 pneumonia episodes in global population (n = 220,000), 1.6 cases/1000 person-year. HIV-infected patients (n = 170) suffered 12 episodes of pneumonia; 46 cases/1000 person-year (relative risk = 29.3, 95% confidence interval, 16.34-51.4; p < 0.01). HIV infected patients with pneumonia have a lower CD4 count (mean 434 versus 230 cells/ml; p = 0.04), higher viral load (4.1 versus 3.2 log copies/ml; p = 0.07) and received antiretroviral treatment in a similar proportion compared to HIV without pneumonia (62 versus a 66.7%, p = 0.5). CONCLUSIONS: Pneumonia in HIV infected patients may be about 30 times more frequent than general population in HAART era. Prevention measures should be reinforced. PMID- 17288934 TI - [Thalidomide and dexamethasone in the treatment of multiple myeloma: progressing step by step]. PMID- 17288935 TI - [Primary care and early identification of high cardiovascular risk]. PMID- 17288936 TI - [Dyggve-Melchior-Clausen syndrome: presentation of a case with a mutation of possible Spanish origin]. AB - BACKGROUND AND OBJECTIVE: The Dyggve-Melchior-Clausen syndrome is a progressive spondyloepimetaphyseal dysplasia characterized by a short trunk dwarfism, barrel chest, sternal protrusion, kyphoscoliosis, severe platyspondyly, with a central constriction, irregular iliac wings with a lacy appearance, rhizomelic shortening of the limbs, microcephaly, coarse face, and variable mental retardation. This condition is extremely rare and the diagnosis is difficult without any previous experience on it. It is inherited as an autosomal recessive condition, its gene (DYM) having been mapped in the 18q12-21.1 chromosomal region. At least 21 different mutations of this gene have been reported. MATERIAL AND METHODS: We describe an affected Spanish child and include his molecular analysis. We also review the current knowledge on this syndrome. RESULTS: The diagnosis of this patient, based on his clinical and radiological features, was later confirmed by analysis of the DYM gene mutations. The patient had two different mutations, one inherited from the mother and the other inherited from the father. CONCLUSIONS: One of the mutations of this patient (exon 8) is extremely rare and has mostly been reported in patients with Spanish ancestors (from Chile, Argentina, Guam islands and a French patient with Spanish ancestors). These observations, together with that of the patient described here, led us to consider this mutation as having a possible Spanish/Portuguese origin. This condition may be more frequent in Spain than previously thought, especially due to misdiagnosis. This is important in order to undertake quaternary prevention, which is quite necessary for rare syndromes with polysystemic affectation. PMID- 17288937 TI - [Dialectics between Internal Medicine and other medical specialties from the professional perspective]. PMID- 17288938 TI - [Prevention of atrial fibrillation in hypertensive patients]. AB - A large percentage of patients with hypertension suffer from atrial fibrillation (AF). The presence of hypertension increases the risk of AF, which in turn aggravates hypertension. The ability of drugs to interfere with specific signal transduction pathways easing the presence of AF in hypertensive patients is promising. To date, the most effective mechanism appears to be the inhibition of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs). This approach is under active investigation. Several trials have assessed the effectiveness of these drugs in the prevention of AF. Data show that both, ACEIs and ARBs, appear effective to prevent AF. However, a lack of prospective randomized double-blind trials data limits their application in absence of any other indication. PMID- 17288939 TI - [Chronic periaortitis presenting with primary arthropathy]. PMID- 17288940 TI - [Residual limb pain and chronic phantom sensation 50 years after amputation]. PMID- 17288941 TI - [Sweet's syndrome and erythema nodosum in a Crohn's disease patient]. PMID- 17288942 TI - [Endoscopic ultrasonography-guided fine needle aspiration in the diagnosis of ganglionic tuberculosis]. PMID- 17288943 TI - [Cesarean section in a patient with Sebastian syndrome]. PMID- 17288944 TI - [Hemidystonia secondary to HIV encephalopathy]. PMID- 17288945 TI - [Pain evaluation as the fifth vital parameter]. PMID- 17288946 TI - [Thoraco-abdominal colateral circulation]. PMID- 17288947 TI - [What is late gadolinium enhancement in hypertrophic cardiomyopathy?]. PMID- 17288948 TI - [Infectious endocarditis: "the microbe makes the difference"]. PMID- 17288949 TI - [Intranodal tachycardia ablation: when physiology is important in the anatomy era]. PMID- 17288950 TI - [Detection and quantification of myocardial fibrosis in hypertrophic cardiomyopathy by contrast-enhanced cardiovascular magnetic resonance]. AB - INTRODUCTION AND OBJECTIVES: Severity of hypertrophic cardiomyopathy has been associated with the amount of myocardial fibrosis in autopsy studies. Cardio vascular magnetic resonance allows, by means of the delayed contrast-enhancement technique, an in vivo detection of focal myocardial fibrosis. Our aim was to study myocardial fibrosis in patients with hypertrophic cardiomyopathy by means of contrast-enhance cardio-vascular magnetic resonance. METHODS: 43 patients (30 males; mean age 47 [18] years) were studied by cardio-vascular magnetic resonance. In all patients left ventricular function and mass was analyzed. Total mass of myocardial fibrosis, as identified by delayed contrast-enhancement, was also calculated. RESULTS: In 63% of patients some degree of myocardial delayed contrast-enhancement was observed, total mass of myocardial fibrosis ranging between 1 and 59 g (mean: 17 g). There was a positive correlation between the amount of myocardial fibrosis and the degree of hypertrophy. Maximal wall thickness was higher in patients with myocardial fibrosis (23 [7] vs 18 [4] mm, respectively, P=.04). Familial cases were also more prevalent among this group (48% vs 13%, respectively), as well as conventional clinical risk factors. CONCLUSIONS: Myocardial fibrosis as detected by contrast-enhanced cardio-vascular magnetic resonance is highly prevalent in hypertrophic cardiomyopathy patients, particularly in familial cases with severe hypertrophy and associated risk factors. PMID- 17288951 TI - [Clinical significance of late gadolinium enhancement on cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy]. AB - INTRODUCTION AND OBJECTIVES: In patients with hypertrophic cardiomyopathy, myocardial fibrosis can be detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. We investigated the relationships between the extent of LGE, left ventricular morphology and function, and clinical characteristics. METHODS: Both cine and gadolinium-enhanced magnetic resonance imaging were performed in 104 patients with hypertrophic cardiomyopathy. RESULTS: Fifty patients (48%) showed LGE (range: 1-11 segments). The extent of LGE was positively correlated with maximum left ventricular wall thickness (r=0.53, P< .001), left ventricular mass (r=0.41, P< .001), and the number of hypokinetic segments (r=0.51, P< .001), and inversely correlated with ejection fraction (r= 0.32, P=.001), the magnitude of the subaortic gradient increase during exercise echocardiography (r=-0.26, P=.023), and age at diagnosis (r=-0.20, P=.04). Four of the five patients with an ischemic response on exercise echocardiography had > or =3 segments showing LGE (P=.003). Severe hypertrophy (i.e., > or =30 mm) and nonsustained ventricular tachycardia occurred more frequently as the number of LGE segments increased (P< .001 and P=.04, respectively). CONCLUSIONS: Extensive LGE reflects greater disease expression. It is associated with more severe myocardial damage (i.e., a lower ejection fraction and a larger number of hypokinetic segments) and with adverse clinical characteristics (e.g., young age at diagnosis, severe hypertrophy, nonsustained ventricular tachycardia, and an ischemic response on exercise), suggesting that it may be closely linked to prognosis. PMID- 17288952 TI - [Acute coronary syndrome in infective endocarditis]. AB - INTRODUCTION AND OBJECTIVES: To describe the clinical, microbiologic, echocardiographic characteristics, and disease progression in patients who experience an acute coronary syndrome during an episode of endocarditis. METHODS: The study included 586 consecutive patients who were diagnosed of infective endocarditis (481 left-sided) at one of five hospitals between 1995 and 2005. RESULTS: Overall, 14 patients (2.9%) had an acute coronary syndrome. Their mean age was 50 (17) years, and 50% had a prosthetic valve. For 11 episodes of endocarditis, laboratory cultures tested positive, with Staphylococcus aureus being the most frequently isolated microorganism. Vegetations were detected by transesophageal echography in 12 cases. The infection was located in the aortic valve in 12 cases. In the 14 patients, periannular complications were found more frequently (11 [78.6%] vs 172 [36.8%]; P=.03), and their size was greater than in other patients. Thirteen had moderate-to-severe valvular regurgitation. In most patients, acute coronary syndrome was an early complication of endocarditis. Myocardial ischemia was due to an embolism in three cases and to coronary artery compression in eight. During follow-up, patients with acute coronary syndrome had higher incidences of heart failure (6 [42.85%] vs 77 [16.48%]; P=.021), cardiogenic shock (5 [35.7%] vs 71 [15.2%]; P=.038), complete atrioventricular block (4 [28.57%] vs 43 [9.2%]; P=.039), and mortality (9 [64.29%] vs 151 [32.33%]; P=.019). CONCLUSIONS: Acute coronary syndrome is usually an early complication of infective endocarditis. It is associated with virulent microorganisms, aortic valve infection, severe valvular regurgitation, extensive periannular complications, and increased mortality. The most frequent cause of myocardial ischemia was coronary artery compression secondary to periannular complications. PMID- 17288953 TI - [Usefulness of incremental atrial pacing for evaluating the effectiveness of the ablation of the slow perinodal pathway]. AB - INTRODUCTION AND OBJECTIVES: To study the usefulness of incremental atrial pacing for evaluating the effect of radiofrequency catheter ablation on slow pathway conduction in patients with atrioventricular (AV) nodal reentrant tachycardia. METHODS: A prospective study was carried out in patients either with (i.e., AV nodal reentrant tachycardia group) or without (i.e., control group) inducible AV nodal reentrant tachycardia who were referred for electrophysiologic study. Incremental atrial pacing involved gradually decreasing the pacing cycle length until the PR interval exceeded the R-R interval (i.e., PR>RR) or AV nodal block occurred. The presence of dual anterograde AV nodal physiology was assessed during programmed atrial stimulation using standard criteria. In the AV nodal reentrant tachycardia group, electrophysiologic study was repeated 30 minutes after successful catheter ablation. RESULTS: In the AV nodal reentrant tachycardia group (n=85), 52 patients (61%) exhibited dual AV nodal physiology during programmed atrial stimulation and 66 (78%) had a PR>RR during incremental atrial pacing. In the control group, the corresponding proportions were 10/56 (18%) and 7/56 (12%), respectively. After successful slow pathway catheter ablation (81/85), 37/81 exhibited dual AV nodal physiology during programmed atrial stimulation while 1/81 had a PR>RR during incremental atrial pacing. The positive predictive value of successful slow pathway ablation for the absence of a PR>RR was 98%. CONCLUSIONS: Incremental atrial pacing demonstrated that the PR interval exceeded the R-R interval in the majority of patients with inducible AV nodal reentrant tachycardia. This technique could provide a fast and simple way of evaluating the effect of radiofrequency catheter ablation on slow pathway conduction. PMID- 17288954 TI - [How many patients admitted for heart failure are eligible for cardiac resynchronization therapy? Analysis of the Andalusian Heart Failure Registry (RAIC) study]. AB - INTRODUCTION AND OBJECTIVES: The objective was to determine what percentage of patients admitted for heart failure met criteria for cardiac resynchronization therapy. METHODS: The study involved registry data on heart failure admissions at 16 public hospitals in Andalusia, Spain between May and July 2004. Criteria for cardiac resynchronization therapy from American College of Cardiology and American Heart Association guidelines were applied: a left ventricular ejection fraction < or = 0.35, New York Heart Association functional class III or IV, and a QRS interval > 120 ms. Outcome was evaluated at 3 months. Multivariate (i.e., logistic regression) analysis was used to identify independent variables associated with meeting resynchronization therapy criteria. RESULTS: The study included 674 patients (43.3% women, mean age 71[11] years). Of these, 5.6% met resynchronization therapy criteria at admission. There was no significant difference in the cardiovascular event rate at 3 months between patients who met resynchronization therapy criteria and those who did not (34.2% vs 23.4%, respectively). Admitting hospital (odds ratio [OR]=0.30, 95% confidence interval [CI], 0.11-0.79), ischemic etiology (OR=2.71, 95% CI, 1.26-5.81), the presence of left bundle branch block (OR=14.97, 95% CI, 5.95-37.64), and mitral regurgitation (OR=4.18, 95% CI, 1.93-9.04) were all independently associated with meeting resynchronization therapy criteria at both admission and short-term follow-up. CONCLUSIONS: The percentage of patients who met cardiac resynchronization therapy criteria was small, but their short-term prognosis was poor. A number of clinical variables associated with meeting resynchronization therapy criteria were identified. PMID- 17288955 TI - [Aortic valve replacement with a Cryolife O'Brien stentless bioprosthesis]. AB - INTRODUCTION AND OBJECTIVES: The Cryolife O'Brien xenograft is a stentless bioprosthesis constructed from noncoronary leaflets from three porcine aortic valves. The aim of this study was to investigate short-term results after aortic valve replacement with this composite xenograft. METHODS: Since October 1993, Cryolife O'Brien bioprostheses have been implanted in 210 patients. The patients' mean age was 70.9 (7.5) years (range 23-83 years). The indication was aortic stenosis in 132 cases, aortic insufficiency in 25 cases, and both lesions in 53 cases. Valve function was studied by echocardiography preoperatively, at discharge, and 6 and 12 months postoperatively. RESULTS: The 30-day mortality rate was 5.2% (11/210). Over time, the mean gradients decreased and the effective area index increased. In addition, the left ventricular mass index, wall thickness, and septum thickness also decreased shortly after surgery. CONCLUSIONS: Use of the Cryolife O'Brien stentless bioprosthesis demonstrated satisfactory results at 1-year follow-up. Additional follow-up is required to assess the performance of this bioprosthesis over the long term. PMID- 17288956 TI - [Acute right atrial and ventricular infarction]. AB - Acute coronary syndromes involving the right side of the heart are associated with increased mortality, a complex clinical course, and lengthy hospitalization, as well as with frequent mechanical and electrical complications. It is important that the signs and symptoms associated with the spread of ischemic disease to the right heart chambers are recognized so that the patient can be given appropriate treatment, which can improve short-term and long-term prognosis. The purpose of this review was to summarize key aspects of the diagnosis, prognosis and treatment of this condition. PMID- 17288957 TI - [Postpartum coronary dissection]. PMID- 17288958 TI - [The superior vena cava as a site of ectopic foci in atrial fibrillation]. AB - Radiofrequency catheter ablation of ectopic foci that trigger atrial fibrillation has been established as a curative method for patients with symptomatic paroxysmal atrial fibrillation. Although the majority of these foci are located in and around the pulmonary veins, other less common locations have been identified. Recognition that foci can lie outside the pulmonary veins is important for ensuring therapeutic success. The most frequently reported foci of ectopic activity outside the pulmonary veins are in the superior vena cava and the posterior wall of the left atrium. Here we report our experience with the ablation of ectopic foci located in the superior vena cava in patients with symptomatic paroxysmal atrial fibrillation. PMID- 17288959 TI - [Ventricular assist devices as a bridge to transplantation]. AB - We carried out an analysis of the results obtained in patients (n=23) who received a ventricular assist device before heart transplantation between 1988 and 2005. Their mean age was 52.5 (8.4) years. Reasons for inclusion in the transplantation waiting list were postcardiotomy referral (n=10), myocardial infarction (n=5), primary graft dysfunction (n=7), and dilated cardiomyopathy (n=1). Different types of ventricular assist device were used: the Abiomed 5000 (n=13), the Biomed Comunidad de Madrid (n=9), and the BioMedicus (n=1). The mean transplantation waiting time was 3.0 (2.4) days. In-hospital complications were neurological (n=7), infectious (n=12), renal (n=3), hemorrhagic (n=3), and respiratory (n=2). In-hospital mortality was 39.1% (n=9). Kaplan-Meier analysis gave a 1-year survival rate of 55.2% and a 5-year survival rate of 32.2%. In patients who were discharged home, the 1-year survival rate was 92.3%. Careful patient selection is essential for obtaining good results. PMID- 17288960 TI - [Axillary artery cannulation with a Dacron graft for surgery of the aortic arch and ascending aorta]. AB - Cannulation of the axillary artery is one possible means of establishing cardiopulmonary bypass during surgery of the ascending aorta and aortic arch. Use of a Dacron graft for cannulation has a number of advantages. In this article, we report our experience with this technique in seven consecutive patients in whom we performed an ascending aorta replacement. The associated procedures involved were aortic root reconstruction using David's procedure in two patients, the Bentall procedure in one, the hemi-arch technique in two, the complete arch and elephant trunk technique in one, aortic valve repair in one, and Valsalva sinus reconstruction in one. Circulatory arrest with antegrade cerebral perfusion was carried out in three cases. There was no in-hospital mortality, and there were no vascular or infectious complications related to axillary access. One patient presented with transient paresthesia of the brachial plexus. In all cases, cardiopulmonary bypass flow was adequate. PMID- 17288961 TI - [Transseptal catheterization using electrophysiological landmarks in ablation procedures]. AB - Since the development of radiofrequency catheter ablation for the treatment of atrial fibrillation, electrophysiology laboratories have experienced a significant rise in the number of transseptal catheterization procedures. Traditionally, the procedure requires the presence of a interventional cardiologist who carries out transseptal catheterization following arterial puncture and placement of a reference pigtail catheter in the aortic root. Use of His bundle and coronary sinus catheters to provide anatomical and electrophysiological landmarks enables transseptal catheterization to be carried out without the need for arterial puncture or intracavity pressure measurement. We report our experience with transseptal catheterization in an electrophysiology laboratory using only electrophysiological landmarks. The procedure was carried out on 68 occasions and was successful in all patients except one, in whom catheterization could not be performed for anatomical reasons and because the patient had previously received anticoagulation therapy. One other patient developed transient ST elevation, which was probably due to an air embolism. PMID- 17288962 TI - [Pseudoaneurysm of the pulmonary autograft following the Ross procedure]. PMID- 17288963 TI - [Hemolytic uremic syndrome due to sirolimus in a heart transplant recipient. Case report]. PMID- 17288964 TI - [Coronary artery disease and percutaneous coronary intervention in a set of twins]. PMID- 17288965 TI - [Arrhythmogenic right ventricular dysplasia in the elderly]. PMID- 17288966 TI - [Kearns-Sayre syndrome: recurrent syncope and atrial flutter]. PMID- 17288968 TI - Epidemiology of osteoporosis. AB - Osteoporotic fractures represent a significant public health burden, which is set to increase in future generations. Lifetime risk is high and lies within the range of 40% to 50% in women and 13% to 22% in men. Life expectancy is increasing worldwide, and it is estimated that the number of individuals aged 65 years and older will increase from the current figure of 323 million to 1555 million by the year 2050. These demographic changes alone can be expected to cause the number of hip fractures occurring worldwide to increase from 1.66 million in 1990 to 6.26 million in 2050. Based on current trends, hip fracture rates might increase in the United Kingdom from 46,000 in 1985 to 117,000 in 2016. The societal cost of these fractures is high; cost-effectiveness analyses showed cost-effectiveness in treating high-risk patients with antiresorptive drugs, particularly if administered as soon as possible after a first fragility fracture. PMID- 17288969 TI - Epidemiology of osteoporosis in rheumatic diseases. AB - Much work has been directed at establishing the impact of osteoporosis and related fragility fractures in rheumatic diseases. Several cross-sectional studies reported that disability and reduced motility that are due to functional impairment are among the most important determinants of bone loss in different rheumatic diseases. At the same time, longitudinal studies have confirmed the detrimental effect of uncontrolled disease activity on bone density. In this perspective, the suppression of inflammation probably remains the main concern when considering treatment options. Besides these variables, pharmacologic agents that are used commonly in the treatment of these conditions probably have an adjunctive effect on bone loss in rheumatic patients. Large epidemiologic studies have demonstrated clearly that patients who have RA, SLE, or AS are at an increased risk for fragility fractures. Further studies are required to investigate the effective impact of osteoporosis and fragility fractures in other rheumatic diseases, and to define the relationship between OA and osteoporosis. A better appreciation of the impact and mechanisms of osteoporosis in rheumatic diseases by rheumatologists represents a clinical challenge; however, a greater understanding of this frequent complication will improve the quality of health care and the lives of patients who have rheumatic diseases. PMID- 17288970 TI - Genetics and osteoporosis. AB - Over the past 10 years, many advances have been made in understanding the mechanisms by which genetic factors regulate susceptibility to osteoporosis. It has become clear from studies in man and experimental animals that different genes regulate BMD at different skeletal sites and in men and women. Linkage studies have identified several chromosomal regions that regulate BMD, but only a few causative genes have been discovered so far using this approach. In contrast, significant advances have been made in identifying the genes that cause monogenic bone diseases, and polymorphic variation is some of these genes has been found to contribute to the genetic regulation of BMD in the normal population. Other genes that have been investigated as possible candidates for susceptibility to osteoporosis because of their role in bone biology, such as vitamin D, have yielded mixed results. Many candidate gene association studies have been underpowered, and meta-analysis has been used to try to confirm or refute potential associations and gain a better estimate of their true effect size in the population. Most of the genetic variants that confer susceptibility to osteoporosis remain to be discovered. It is likely that new techniques such as whole-genome association will provide new insights into the genetic determinants of osteoporosis and will help to identify genes of modest effect size. From a clinical standpoint, genetic variants that are found to predispose to osteoporosis will advance our understanding of the pathophysiology of the disease. They could be developed as diagnostic genetic tests or form molecular targets for design of new drugs for the prevention and treatment of osteoporosis and other bone diseases. PMID- 17288971 TI - Recommendations for measurement of bone mineral density and identifying persons to be treated for osteoporosis. AB - Clinical practice guidelines exist for the diagnosis and treatment of osteoporosis in men and postmenopausal women. These guidelines present a uniform set of recommendations. Unfortunately, studies have shown a low rate of screening and treatment, particularly in high-risk groups, such as patients who have experienced a fracture. It is hoped that quality improvement projects, such as that being conducted by the American Medical Association in conjunction with numerous specialty societies, will lead to an improvement in physician practices in this area that will result in a reduction in morbidity and mortality from osteoporotic fractures. PMID- 17288972 TI - Emerging issues with bisphosphonates. AB - Bisphosphonates are the most commonly used agents in the management of metabolic bones diseases. Despite their established therapeutic value, a number of points of uncertainty remain, particularly in connection with their optimal long-term use. It is likely that definitive clinical trial data will not become available to resolve these questions, so careful clinical observation and caution are needed in patients who require treatment over periods of more than 10 years. PMID- 17288973 TI - Parathyroid hormone update. AB - PTH is an exciting new treatment option for postmenopausal women and hypogonadal men who have osteoporosis. As an anabolic agent that affects bone metabolism, it represents an entirely new class of medication for osteoporosis and a novel approach to reducing fracture risk. Numerous clinical trials have demonstrated increases in trabecular and cortical BMD (trabecular more than cortical) in men and women, and reduction in vertebral and nonvertebral fractures in postmenopausal women. Studies suggest that it is safe for use for up to 2 years, but further studies are needed to tes longer intervals of use. Although the combination of PTH and bisphosphonates does not seem to be additive, sequential therapy of PTH followed by bisphosphonate yields maximum gains in BMD compared with combined use or monotherapy with antiresorptive agents. As our knowledge of PTH grows, this is an exciting time for researchers, clinicians, and patients who study, treat, and live with the devastating consequences of progressive osteoporosis. PMID- 17288974 TI - Adherence to medications for the treatment of osteoporosis. AB - Although there is a wide variety of osteoporosis medications with varying dosing intervals, adherence to therapies for postmenopausal- or glucocorticoid-induced osteoporosis remains poor. It is associated with long-term consequences, such as increased osteoporotic fractures, including nonvertebral hip fractures. There is a lack of understanding about why patients are not staying on therapy. Potential solutions include newer medications with extended dosing intervals, monitoring, and an open physician-patient relationship. PMID- 17288975 TI - Glucocorticoid-induced osteoporosis: mechanisms and therapeutic approach. AB - GCs constitute a therapeutic class largely used in clinical medicine for the curative or supportive treatment of various conditions involving the intervention of numerous medical specialties. Beyond their favorable therapeutic effects, GCs almost invariably provoke bone loss and a rapid increase in bone fragility, with its host of fractures. Men and postmenopausal women constitute a preferential target for the bone complications of GCs. The premenopausal status is not, however, a shelter; bone loss also happens in young women who are on GCs. Exposure to GCs yields a fracture risk exceeding the risk conferred by a low BMD per se. Therefore, some reason exists to settle the BMD threshold for therapeutic intervention not at -2.5 T-scores but at -1.0 or -1.5 T-scores, even if no prospective randomized trial so far endorses that opinion. Nowadays, bisphosphonate therapy should be proposed to every patient at risk for fragility fracture, along with calcium and vitamin D supplementation. Studies of other therapeutic modalities (eg, promoters of bone formation) are in progress. PMID- 17288977 TI - Predominance of Trypanosoma cruzi I among Panamanian sylvatic isolates. AB - Trypanosoma cruzi is throughout Panama, which is in agreement with the widespread of the sylvatic vectors implicated in the transmission. Eco-epidemiological changes in some regions of the country have led to a successful dissemination of the palm-tree Attalea butyracea and a possible adaptation of the primary vector of Chagas' disease to human settlements. These facts might increase both vector human contact and human infection with different potentials T. cruzi genotypes and make therefore necessary a study to disclose Panamanian T. cruzi make-up. In this study, 71 T. cruzi isolates from Rhodnius pallescens were analyzed using mini-exon gene and sequence-characterized amplified region markers. The analyzed strains were T. cruzi lineage I. This finding along with prior results indicates that T. cruzi I is the principal genotype circulating in both sylvatic and domestic/peridomestic cycles and consequently responsible for the disease in the country. PMID- 17288976 TI - Inflammation-induced bone loss: can it be prevented? AB - Inflammatory synovitis induces profound bone loss and OCLs are the instrument of this destruction. TNF blockers have an established role in the prevention of inflammatory bone loss in RA; however, not all patients respond to anti-TNF therapy and side effects may prevent long-term treatment in others. The B-cell- depleting antibody rituximab and the T-cell costimulation blocker abatacept are emerging as major treatment options for patients who are resistant to anti-TNF [96,97]. Proof-of-concept studies demonstrate that targeting RANK-mediated osteoclastogenesis prevents inflammatory bone loss and clinical application has only just begun. The efficacy of RANKL inhibition has been witnessed in trials of Denosumab, and RANKL-neutralizing antibodies are likely to become the treatment of choice for blocking RANKL in RA [77,78]. A major limitation of RANKL antagonism is that it does not treat synovitis. Therefore, anti-RANKL therapy most likely will be used in the context of MTX therapy. There is uncertainty about the possible extraskeletal adverse effects of long-term effects of long term RANKL blockade. In particular, anti-RANKL therapy could jeopardize dendritic cell function or survival. The demonstrable role of OCLs in inflammation-induced bone loss also invites a reconsideration of the new BPs for bone protection [98]. Studies of ZA in preclinical models indicate that bone protection is comparable to that afforded by OPG. One possible caveat is that intravenous BPs are linked to jaw osteonecrosis [99], although the incidence is confined mainly to intensive treatment in the oncology setting. Although pulsed PTH stimulated bone formation in arthritic models, it has yet to be proven clinically in the context of powerful OCL inhibition with TNF or RANKL antagonists. With strategies that normalize OCL numbers, clinicians are poised to accomplish effective prevention of inflammation-induced bone loss. PMID- 17288978 TI - Combination of peptide nucleic acid beacon and nuclease S1 for clear-cut genotyping of single nucleotide polymorphisms. PMID- 17288979 TI - Affinity profiling using the peptide microarray technology: a case study. AB - Little about the reliability of measurements obtained using synthetic peptide microarrays is known. We report results from a study on the quantitative reliability of microarrays manufactured by robot-supported immobilization of presynthesized peptides for different microarray platforms. Technological precision is assessed for inter- and intra-device readout comparisons. Correlations between measured signals and known dissociation constants using a phenomenological model derived from the mass action law are discussed. Special emphasis is on discussing the pitfalls of high-throughput affinity measurements. We show that the quantitative determination of binding affinities is prone to be biased toward a mean affinity of around 10(-7)M, while the classification of peptides into either "binders" or "nonbinders" provides very high prediction accuracy. The experimental requirements needed to obtain reliable binding affinity predictions are discussed. PMID- 17288980 TI - A fluorescence-resonance-energy-transfer-based protease activity assay and its use to monitor paralog-specific small ubiquitin-like modifier processing. AB - Dynamic modification of proteins with the small ubiquitin-like modifier (SUMO) affects the stability, cellular localization, enzymatic activity, and molecular interactions of a wide spectrum of protein targets. We have developed an in vitro fluorescence-resonance-energy-transfer-based assay that uses bacterially expressed substrates for the rapid and quantitative analysis of SUMO paralog specific C-terminal hydrolase activity. This assay has applications in SUMO protease characterization, enzyme kinetic analysis, determination of SUMO protease activity in eukaryotic cell extracts, and high-throughput inhibitor screening. In addition, while demonstrating such uses, we show that the SUMO-1 processing activity in crude HeLa cell extracts is far greater than that of SUMO 2, implying that differential maturation rates of SUMO paralogs in vivo may be functionally significant. The high degree of structural conservation across the ubiquitin-like protein superfamily suggests that the general principle of this assay should be applicable to other post-translational protein modification systems. PMID- 17288981 TI - Natural substrate assay for chitinases using high-performance liquid chromatography: a comparison with existing assays. AB - The determination of kinetic parameters of chitinases using natural substrates is difficult due to low K(m) values, which require the use of low substrate concentrations that are hard to measure. Using the natural substrate (GlcNAc)(4), we have developed an assay for the determination of k(cat) and K(m)values of chitinases. Product concentrations as low as 0.5 microM were detected using normal-phase high-performance liquid chromatography (HPLC) with an amide 80 column (0.20 x 25 cm) using spectrophotometric detection at 210 nm. By means of this assay, k(cat) and K(m)values for chitinases A (ChiA) and B (ChiB) of Serratia marcescens were found to be 33+/-1s(-1) and 9+/-1 microM and 28+/-2s(-1) and 4+/-2 microM, respectively. For ChiB, these values were compared to those found with commonly used substrates where the leaving group is a (nonnatural) chromophore, revealing considerable differences. For example, assays with 4 methylumbelliferyl-(GlcNAc)(2) yielded a k(cat) value of 18+/-2s(-1) and a K(m) value of 30+/-6 microM. For two ChiB mutants containing a Trp --> Ala mutation in the +1 or +2 subsites, the natural substrate and the 4-methylumbelliferyl (GlcNAc)(2) assays yielded rather similar K(m) values (5-fold difference at most) but showed dramatic differences in k(cat) values (up to 90-fold). These results illustrate the risk of using artificial substrates for characterization of chitinases and, thus, show that the new HPLC-based assay is a valuable tool for future chitinase research. PMID- 17288982 TI - A plate reader method for the measurement of NAD, NADP, glutathione, and ascorbate in tissue extracts: Application to redox profiling during Arabidopsis rosette development. AB - Glutathione, NAD, and NADP are key nonprotein redox couples in the aqueous phase of virtually all cells, whereas in plant cells ascorbate also plays an important role in redox homeostasis. This work presents the development and validation of plate reader assays that allow rapid analysis of these four redox couples in extracts of Arabidopsis leaves. Analytical methods were adapted and validated for specific measurement of oxidized and reduced forms. Oxidized and reduced forms of glutathione and ascorbate, as well as NAD(+) and NADP(+), were measured in HCl extracts, NADH, and NADPH in parallel alkaline extracts. Both standards and extracts gave linear assay responses, and recovery quotients of added metabolites through the extraction procedure were generally high. The plate reader method was validated against more conventional spectrophotometric assays and also, for glutathione, by HPLC analysis. The method was shown to yield quantitative data for six independent extracts with a total sample preparation and analysis time of 4h. Analysis of the four redox couples throughout Arabidopsis rosette development showed that redox states were relatively constant but that total pools of NAD, glutathione, and ascorbate were significantly modified by day length and developmental stage. PMID- 17288983 TI - A sensitive nonenzymatic glucose sensor in alkaline media with a copper nanocluster/multiwall carbon nanotube-modified glassy carbon electrode. AB - Copper (Cu) nanoclusters were electrochemically deposited on the film of a Nafion solubilized multiwall carbon nanotube (CNTs)-modified glassy carbon electrode (CNTs-GCE), which fabricated a Cu-CNTs composite sensor (Cu-CNTs-GCE) to detect glucose with nonenzyme. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used for the characterization of the distribution of the Cu nanoclusters on the CNTs matrix. The composite of the Cu-CNTs was investigated by the electrochemical characterization of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The preliminary study shows that the nonenzymatic sensor has synergistic electrocatalytic activity to the oxidation of glucose in alkaline media. A well applicable sensor was constructed to use for the analysis of the glucose in real blood serum samples due to the large number of electrons taking part in the oxidation process, the high apparent kinetic rate constant, and the stable operation of the electrode. The linear range for the detection of the glucose is 7.0 x 10(-7) to 3.5 x 10(-3) M with a high sensitivity of 17.76 microA mM(-1), a low detection limit of 2.1 x 10(-7) M, and a fast response time of within 5s. Experiment results also showed that the sensor has good reproducibility and long-term stability and is interference free. PMID- 17288984 TI - A technique to isolate DNA from woody and herbaceous plants by using a silica based plasmid extraction column. PMID- 17288985 TI - Translational control of apolipoprotein B mRNA via insulin and the protein kinase C signaling cascades: evidence for modulation of RNA-protein interactions at the 5'UTR. AB - The link between hepatic insulin signaling and apolipoprotein B (apoB) production has important implications in understanding the etiology of metabolic dyslipidemia commonly observed in insulin-resistant states. Recent studies have revealed important translational mechanisms of apoB mRNA involving the 5' untranslated region (5'UTR) and insulin-mediated translational suppression via an insulin-sensitive RNA binding protein. Here, we have investigated the role of the protein kinase C (PKCs) signaling cascade in the regulation of apoB mRNA translation, using a series of chimeric apoB UTR-luciferase constructs, in vitro translation of UTR-luciferase cRNAs, and metabolic labeling of intact HepG2 cells. The PKC activator, phorbol 12-myristate 13-acetate (PMA), increased luciferase expression of constructs containing the apoB 5' UTR whereas treatment with Bis-I, a general PKC inhibitor or Go6976, a more specific PKC alpha/beta inhibitor, decreased expression, under both basal and insulin-treated conditions. These effects were confirmed to be translational in nature based on in vitro translation studies of T7 apoB UTR-luciferase constructs transcribed and translated in vitro in the presence of HepG2 cytosol treated with insulin or signaling modulators. Mobility shift experiments using cytosol treated with either PKC inhibitor (Bis-I) or activator (PMA) showed parallel changes between translation of apoB 5'UTR-luciferase constructs and the binding of a protein(s) complex migrating around 110 kDa to the apoB 5' UTR. ApoB mRNA levels were unaltered under these conditions based on real-time PCR analysis. Bis-I and Go6976 were both able to significantly decrease newly synthesized apoB100 protein in the presence or absence of insulin. Overall, the data suggests that PKC activation may induce increased mRNA translation and synthesis of apoB100 protein through a mechanism involving the interaction of trans-acting factors with the apoB 5'UTR. We postulate potential links between PKC activation as seen in insulin-resistant/diabetic states, enhanced translation of apoB mRNA, and hepatic VLDL-apoB overproduction. PMID- 17288987 TI - Activated alpha(2)-macroglobulin induces cell proliferation and mitogen-activated protein kinase activation by LRP-1 in the J774 macrophage-derived cell line. AB - The low-density lipoprotein receptor-related protein-1 (LRP-1) is an endocytic receptor of activated forms of the proteinase inhibitor alpha(2)-macroglobulin (alpha(2)M*). It has been proposed that alpha(2)M* and LRP-1 modulate diverse cellular processes, including cell adhesion, proliferation, and migration, which are involved in inflammation and tumor progression. However, relatively little is known about the role of alpha(2)M*/LRP-1 interaction on these processes. In this work, we demonstrate that alpha(2)M* binding to LRP-1 induces cell proliferation and MAPK activation in the J774 macrophage-derived cell line, which were blocked by RAP, an antagonist of LRP-1-binding ligands, and by PD980059, a specific inhibitor for the Mek1-ERK1/2 pathway. In addition, we demonstrate that LPS, a bacterial product that it is known to down-regulate the LRP-1 expression on macrophage, abrogated the signaling activity triggered by alpha(2)M* on LPS treated J774 cells. These results suggest that alpha(2)M*/LRP-1 interaction constitutes a key role in the macrophage functioning during inflammation and cancer. PMID- 17288986 TI - An architectural perspective of vitamin D responsiveness. AB - Vitamin D serves as a principal modulator of skeletal gene transcription, thus necessitating an understanding of interfaces between the activity of this steroid hormone and regulatory cascades that are functionally linked to the regulation of skeletal genes. Physiological responsiveness requires combinatorial control where coregulatory proteins determine the specificity of biological responsiveness to physiological cues. It is becoming increasingly evident that the regulatory complexes containing the vitamin D receptor are dynamic rather than static. Temporal and spatial modifications in the composition of these complexes provide a mechanism for integrating regulatory signals to support positive or negative control through synergism and antagonism. Compartmentalization of components of vitamin D control in nuclear microenvironments supports the integration of regulatory activities, perhaps by establishing thresholds for protein activity in time frames that are consistent with the execution of regulatory signaling. PMID- 17288988 TI - Influence of jaw gape on EMG of jaw muscles and jaw-stretch reflexes. AB - The influence of jaw gapes on jaw-stretch reflexes and jaw muscles activity was studied in order to test the sensitivity of human muscle spindle afferents in various jaw muscles. Twelve healthy men (mean age+/-S.E.M.: 25.0+/-1.2yr) participated in the study. Short-latency excitatory reflex responses were evoked by a custom-made stretch device with the subjects biting on a jaw-bar with their front teeth. Surface electromyographic (sEMG) recordings from right masseter (MAR), and right temporalis (TAR), intramuscular EMG (imEMG) recordings from right lateral pterygoid (LPR) and right anterior digastric (ADR) muscles were made. The reflex at different jaw gapes of 6, 10, 14, 18, 22, 26, 30, 34, and 38mm were examined in random order with standard stretch conditions of 1mm displacement and 10ms ramp time. Twenty sweeps of the reflex were recorded at each level with at least 5s interval between each sweep with online monitoring of the visual feed back at 15% of maximum voluntary contraction (MVC) of each jaw gape from MAR. The results showed that the peak-to-peak amplitude of the jaw stretch reflex in MAR was significantly higher at 14mm compared to 30, 34, and 38mm (P<0.038), whereas the reflex amplitude in TAR increased with jaw gape until a maximum at 34mm. There was no significant effect of jaw gape in LPR muscles (P=0.825) and no obvious stretch reflex was observed in ADR. When the amplitude was normalised to the pre-stimulus EMG at each jaw gape, the highest normalised amplitude was observed at 14mm jaw gape in MAR, however there was no significant effect of jaw gape on the normalised amplitude in TAR and LPR. In addition, masseter EMG at MVC significantly decreased with the increase of the gapes, i.e. biting at 6, 14, and 18mm gapes had a significantly higher MVC compared to 26, 30, 34, and 38mm (ANOVA: P<0.013). It is concluded that the jaw gapes influence the sensitivity of the human muscle spindle afferents in jaw-closing muscles with a distinct peak, which is within normal jaw gapes during function. PMID- 17288989 TI - Pain and the rate of dentinal fluid flow produced by hydrostatic pressure stimulation of exposed dentine in man. AB - OBJECTIVE: To determine the relationship between pain intensity and the rate of fluid flow through dentine in human subjects. DESIGN: The experiments were carried out on 16 premolars in 13 human subjects (aged 15-25 years). Dentine was exposed at the tip of the buccal cusp, etched with acid and covered with saline. A series of 5 s hydrostatic pressure stimuli between 400 mmHg above and 400 mmHg below atmospheric were applied to the dentine, in steps of 50 mmHg. The subject indicated the intensity of any pain produced on a visual analogue scale (VAS). The fluid flow through dentine during application of the same stimuli was measured in vitro within 3 h after tooth extraction. RESULTS: The median pain threshold with negative (subatmospheric) stimuli was -125 mmHg and, with positive pressure stimuli, 200 mmHg, which corresponded to dentinal fluid flow rates of 3.29 nL/(s mm(2)) exposed dentine and 5.75 nL/(s mm(2)), respectively. Both the median pressure and the mean rate of flow at threshold with negative pressures were significantly lower than with positive pressures. The curves relating VAS score to stimulus intensity were similar with both negative and positive pressures. CONCLUSION: The sensory transduction mechanism for pain in human teeth is more sensitive to outward than inward flow through dentinal tubules. The difference in sensitivity was however much less than that of the hydrodynamic receptors in the cat, which respond very much more strongly to negative than positive pressure stimuli. PMID- 17288990 TI - Narrative exposure therapy for political imprisonment-related chronic posttraumatic stress disorder and depression. AB - The psychological consequences of traumatic stress may last even into old age. In persons in their 60s and 70s who had been victims of political detention and torture four decades ago, we compared the outcome of narrative exposure therapy (NET) to that of psychoeducation (PED) only. From a group of 59 former political detainees, 18 who fulfilled the full PTSD criteria according to the Composite International Diagnostic Interview (CIDI) were offered and accepted participation in the treatment study. The participants were randomly assigned to either one session of PED (n=9) or five sessions of NET (n=9). Symptoms of PTSD (CIDI) and depression (Beck Depression Inventory, BDI) were assessed prior to treatment and after a 6-month follow-up. NET but not PED produced a significant reduction in post-traumatic symptoms and depression scores. Four out of 9 of those who completed NET, compared to 8/9 of those within the PED group, still had PTSD 6 months after the treatment had ended. These results indicate that NET may lead to the alleviation of post-traumatic and depression symptoms even when the conditions persist for excessive time periods. PMID- 17288991 TI - HuR binds to a single site on the C/EBPbeta mRNA of 3T3-L1 adipocytes. AB - HuR is a ligand for nuclear mRNAs containing adenylate-uridylate rich elements in the 3'-untranslated region. Once bound to the mRNA, HuR is recognized by adapter proteins which then facilitate nuclear export of the complex. In the cytosol HuR is thought to function to control stability and translation of its ligand message. In the 3T3-L1 cells HuR is constitutively expressed and localized predominantly to the nucleus in the preadipocytes. However within 30 min of exposure to the differentiation stimulus, the HuR content in the cytosol increases consistent with HuR regulating the availability of relevant mRNAs for translation. Using in vitro RNA gel shifts, we have demonstrated that the C/EBPbeta message is a ligand for HuR and that the single binding site is an adenylate-uridylate rich element in the 3'-untranslated region. PMID- 17288992 TI - Plant protein phosphorylation monitored by capillary liquid chromatography- element mass spectrometry. AB - Many essential cellular functions such as growth rate, motility, and metabolic activity are linked to reversible protein phosphorylation, since they are controlled by signaling cascades based mainly on phosphorylation/dephosphorylation events. Quantification of global or site specific protein phosphorylation is not straightforward with standard proteomic techniques. The coupling of capillary liquid chromatography (microLC) with ICP-MS (inductively coupled plasma-mass spectrometry) is a method which allows a quantitative screening of protein extracts for their phosphorus and sulfur content, and thus provides access to the protein phosphorylation degree. In extension of a recent pilot study, we analyzed protein extracts from the model organisms Arabidopsis thaliana and Chlamydomonas reinhardtii as representatives for multicellular and unicellular green photosynthetically active organisms. The results indicate that the average protein phosphorylation level of the algae C. reinhardtii is higher than that of A. thaliana. Both the average phosphorylation levels were found to be between the extreme values determined so far for prokaryotes (C. glutamicum, lowest levels) and eukaryotes (Mus musculus, highest levels). Tissue samples of A. thaliana representing different stages of plant development showed varying levels of protein phosphorylation indicating a different adjustment of the kinase/phosphatase system. We also utilized the microLC-ICP-MS technology to estimate the efficiency of a novel phosphoprotein enrichment method based on aluminum hydroxide, since the enrichment of phosphorylated species is often an essential step for their molecular characterization. PMID- 17288993 TI - Crystal structure and RNA-binding analysis of the archaeal transcription factor NusA. AB - The transcription factor NusA functions in transcriptional regulation involving termination in bacteria. A NusA homolog consisting of only the two KH domains is widely conserved in archaea, but its function remains unknown. We have found that Aeropyrum pernix NusA strongly binds to a certain CU-rich sequence near a termination signal. Our crystal structure of A. pernix NusA revealed that its spatial arrangement is quite similar to that of the KH domains of bacterial NusA. Thus, we consider archaeal NusA to have retained some functions of bacterial NusA, including the ssRNA-binding ability. Remarkable structural differences between archaeal and bacterial NusA exist at the interface with RNAP, in connection with the different NusA-binding sites around the termination signals. Transcriptional termination in archaea could differ from all of the known bacterial and eukaryal mechanisms, in terms of the combination of a bacterial factor and a eukaryal-type RNAP. PMID- 17288994 TI - 3D model of RNA polymerase and bidirectional transcription. AB - In the in vitro mitochondrial (mt) transcription initiation system with mt RNA polymerase fraction and mt lysate, the transcription initiation products were shown to be synthesized bidirectionally from the only H-strand-promoter (HSP)/L strand-promoter region (LSP) of the mitochondrial D-loop genome segment. These transcription products ranged between >100 and >800 bp with the purified mitochondrial RNA polymerase fraction, but were larger (>2030-4000 bp) in size with the mitochondrial lysate in both human and mouse. In this brief report, an in vitro reconstituted mitochondrial transcription system purified by affinity chromatography (heparin-Sepharose) from mouse hypotetraploid letter Ehrlich ascites tumor cell mitochondria was shown to initiate transcription bidirectionally from the mitochondrial D-loop region (HSP/LSP), as evidenced by in vitro generated transcription products. The in vitro generated transcription products were separated by sequencing gel. But this in vitro reconstituted transcription system was not studied beyond the D-loop region. A 3D model of the enzyme RNA polymerase was docked with both ATP and CTP. PMID- 17288995 TI - The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders. AB - Brain histaminergic neurons play a prominent role in arousal and maintenance of wakefulness (W). H(3)-receptors control the activity of histaminergic neurons through presynaptic autoinhibition. The role of H(3)-receptor antagonists/inverse agonists (H(3)R-antagonists) in the potential therapy of vigilance deficiency and sleep-wake disorders were studied by assessing their effects on the mouse cortical EEG and sleep-wake cycle in comparison to modafinil and classical psychostimulants. The H(3)R-antagonists, thioperamide and ciproxifan increased W and cortical EEG fast rhythms and, like modafinil, but unlike amphetamine and caffeine, their waking effects were not accompanied by sleep rebound. Conversely, imetit (H(3)R-agonist) enhanced slow wave sleep and dose-dependently attenuated ciproxifan-induced W, indicating that the effects of both ligands involve H(3) receptor mechanisms. Additional studies using knockout (KO) mice confirmed the essential role of H(3)-receptors and histamine-mediated transmission in the wake properties of H(3)R-antagonists. Thus ciproxifan produced no increase in W in either histidine-decarboxylase (HDC, histamine-synthesizing enzyme) or H(1)- or H(3)-receptor KO-mice whereas its waking effects persisted in H(2)-receptor KO mice. These data validate the hypothesis that H(3)R-antagonists, through disinhibition of H(3)-autoreceptors, enhancing synaptic histamine that in turn activates postsynaptic H(1)-receptors promoting W. Interestingly amphetamine and modafinil, despite their potent arousal effects, appear unlikely to depend on histaminergic mechanism as their effects still occurred in HDC KO-mice. The present study thus distinguishes two classes of wake-improving agents: the first acting through non-histaminergic mechanisms and the second acting via histamine and supports brain H(3)-receptors as potentially novel therapeutic targets for vigilance and sleep-wake disorders. PMID- 17288997 TI - Catalog of the Neurological Mutants of Mouse revisited: honoring the 40th anniversary of its initial publication. PMID- 17288996 TI - Spatial attention facilitates selection of illusory objects: evidence from event related brain potentials. AB - The relationship between spatial attention and object-based attention has long been debated. On the basis of behavioral evidence it has been hypothesized that these two forms of attention share a common mechanism, such that directing spatial attention to one part of an object facilitates the selection of the entire object. In a previous study (Martinez, A., Teder-Salejarvi, W., Vazquez, M., Molholm, S., Foxe, J.J., Javitt, D.C., Di Russo, F., Worden, M.S., Hillyard, S.A., 2006. "Objects are highlighted by spatial attention." J. Cogn. Neurosci. 18(2): 298-310) we used recordings of event-related potentials (ERPs) during a paradigm modeled after that of Egly et al. (Egly, R., Driver, J., Rafal, D.R., 1994. Shifting visual attention between objects and locations: evidence from normal and parietal lesion subjects. J. Exp. Psychol. Gen. 123(2) 161-77) to investigate this relationship. As reported in numerous studies of spatial attention, we found the typical pattern of enhanced neural activity in visual cortex elicited by attended stimuli. Unattended stimuli belonging to the same object as the attended stimuli elicited a very similar spatiotemporal pattern of enhanced neural activity that was localized to lateral occipital cortex (LOC). This similarity was taken as evidence that spatial- and object-selective attention share, at least in part, a common neural mechanism. In the present study we further investigate this relationship by examining whether this spread of spatial attention within attended objects can be guided by objects defined by illusory contours. Subjects viewed a display consisting of two illusory rectangular objects and directed attention to continuous sequences of stimuli (brief onsets) at one end of one of the objects. Stimuli occurring at irrelevant locations but belonging to the same attended object elicited larger posterior N1 amplitudes than that elicited by unattended objects forming part of a different object. This object-selective N1 enhancement was localized to lateral occipital cortex. The present data support the hypothesis that the allocation of spatial attention can be guided by illusory object boundaries and that this allocation strengthens the perceptual representations of attended objects at the level of visual area LOC. PMID- 17288998 TI - The central amygdala regulates sodium intake in sodium-depleted rats: role of 5 HT3 and 5-HT2C receptors. AB - In the present paper, we have evaluated the participation of 5-HT(3) and 5-HT(2C) receptors in the central amygdala (CeA) in the regulation of water and salt intake in sodium-depleted rats. m-CPBG-induced pharmacological activation of 5 HT(3) receptors located in the CeA resulted in a significant reduction in salt intake in sodium-depleted rats. This antinatriorexic effect of m-CPBG was reverted by pretreatment with the selective 5-HT(3) receptor antagonist ondansetron. The injection of ondansetron alone into the CeA had no effect on sodium-depleted and normonatremic rats. Conversely, pharmacological stimulation of 5-HT(2C) receptors located in the central amygdala by the selective 5-HT(2C) receptor agonist m-CPP failed to modify salt intake in sodium-depleted rats. Additionally, the administration of a selective 5-HT(2C) receptor blocker, SDZ SER 082, failed to modify salt intake in rats submitted to sodium depletion. These results lead to the conclusion that the pharmacological activation of 5 HT(3) receptors located within the CeA inhibits salt intake in sodium-depleted rats and that 5-HT(2C) receptors located within the CeA appear to be dissociated from the salt intake control mechanisms operating in the central amygdala. PMID- 17288999 TI - Effects of acute heat exposure on prosencephalic c-Fos expression in normohydrated, water-deprived and salt-loaded rats. AB - In the present study, the distribution pattern of c-Fos protein immunoreactivity (Fos-IR) in prosencephalic areas of the brain involved in thermoregulatory and osmoregulatory responses was investigated, in rats exposed or not exposed to a hyperthermic environment, under three different conditions: normohydration, dehydration induced by water deprivation and hyperosmolarity induced by an acute intragastric salt load. Normohydrated, water-deprived or salt-loaded male Wistar rats (270+/-30 g) were submitted or not to acute heat exposure (33 degrees C for 45 min). A separate group of animals was submitted to the same experimental protocol and had blood samples collected before and after the heating period to measure serum osmolarity and sodium. The brains were processed for c-Fos immunohistochemistry using the avidin-biotin peroxidase method. After analyzing Fos-IR in the brains of animals in the present study, three different types of prosencephalic areas were identified: (1) those that respond to hydrational and to heat conditions, with an interaction between these two factors (PaMP and SON); (2) those that respond to hydrational and to heat conditions, but with no interaction between these factors (MnPO, LSV and OVLT); and (3) those that respond only to hydrational status (SFO and PaLM). PMID- 17289000 TI - Role of the amygdala in ethanol withdrawal seizures. AB - Ethanol withdrawal (ETX) after induction of ethanol dependence results in a syndrome that includes enhanced seizure susceptibility. During ETX in rodents, generalized audiogenic seizures (AGS) can be triggered by intense acoustic stimulation. Previous studies have implicated specific brainstem nuclei in the neuronal network that initiates and propagates AGS during ETX. Although ethanol and ETX are known to affect amygdala neurons, involvement of the amygdala in the network subserving AGS is unclear. Since ethanol and ETX affect N-methyl-d aspartate (NMDA) receptors in the amygdala, the present study evaluated the effect of focally microinjecting a NMDA antagonist into the amygdala of rats treated with a binge protocol (intragastric administration of ethanol 3 times daily for 4 days). Separate experiments examined extracellular neuronal firing in the amygdala. Cannulae or microwire electrodes were chronically implanted into the amygdala, and changes in seizure behaviors and/or extracellular action potentials were evaluated. Bilateral focal microinjection of a NMDA antagonist, 2 amino-7-phosphonoheptanoate (AP7), into either central nucleus or lateral nucleus of the amygdala (LAMG) significantly reduced AGS. The doses of AP7 and time course of effect were similar in each site, suggesting that both amygdala nuclei participate in the AGS network. Acoustic responses of LAMG neurons were significantly decreased 1 h after the first ethanol dose and also during ETX, as compared to pre-binge controls. However, LAMG neurons consistently exhibited rapid tonic firing during the generalized tonic convulsions of AGS. These findings suggest a critical role of the amygdala in the ETX seizure network in generating tonic convulsions during AGS. PMID- 17289002 TI - Estrogen regulation of neurotrophin expression in sympathetic neurons and vascular targets. AB - We hypothesize that estrogen exerts a modulatory effect on sympathetic neurons to reduce neural cardiovascular tone and that these effects are modulated by nerve growth factor (NGF), a neurotrophin that regulates sympathetic neuron survival and maintenance. We examined the effects of estrogen on NGF and tyrosine hydroxylase (TH) protein content in specific vascular targets. Ovariectomized, adult Sprague-Dawley rats were implanted with placebo or 17beta-estradiol (release rate, 0.05 mg/day). Fourteen days later, NGF levels in the superior cervical ganglia (SCG) and its targets, the heart, external carotid artery, and the extracerebral blood vessels, as well as estrogen receptor alpha (ERalpha) content levels in the heart, were determined using semi-quantitative Western blot analysis. TH levels in the SCG and extracerebral blood vessels were determined by Western blotting and immunocytochemistry, respectively. Circulating levels of 17beta-estradiol and prolactin (PRL) were quantified by RIA. Estrogen replacement significantly decreased NGF protein in the SCG and its targets, the external carotid artery, heart and extracerebral blood vessels. TH protein associated with the extracerebral blood vessels was also significantly decreased, but ERalpha levels were significantly increased in the heart following estrogen replacement. These results indicate that estrogen reduces NGF protein content in sympathetic vascular targets, which may lead to decreased sympathetic innervations to these targets, and therefore reduced sympathetic regulation. In addition, the estrogen induced increase in ERalpha levels in the heart, a target tissue of the SCG, suggests that estrogen may sensitize the heart to further estrogen modulation, and possibly increase vasodilation of the coronary vasculature. PMID- 17289001 TI - Selective septohippocampal - but not forebrain amygdalar - cholinergic dysfunction in diencephalic amnesia. AB - A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), was used to investigate diencephalic-limbic interactions. In-vivo acetylcholine (ACh) efflux, a marker of memory-related activation, was measured in the hippocampus and the amygdala of PTD-treated and pair-fed (PF) control rats while they were tested on a spontaneous alternation task. During behavioral testing, all animals displayed increases in ACh efflux in both the hippocampus and amygdala. However, during spontaneous alternation testing ACh efflux in the hippocampus and the alternation scores were higher in PF rats relative to PTD treated rats. In contrast, ACh efflux in the amygdala was not suppressed in PTD treated rats, relative to PF rats, prior to or during behavioral testing. In addition, unbiased stereological estimates of the number of choline acetyltransferase (ChAT) immunopositive neurons in the medial septal/diagonal band (MS/DB) and nucleus basalis of Meynert (NBM) also reveal a selective cholinergic dysfunction: In PTD-treated rats a significant loss of ChAT immunopositive cells was found only in the MS/DB, but not in the NBM. Significantly, these results demonstrate that thiamine deficiency causes selective cholinergic dysfunction in the septo-hippocampal pathway. PMID- 17289003 TI - Injection of mouse and human neural stem cells into neonatal Niemann-Pick A model mice. AB - Cloned mouse C17.2 neural stem cells (NSCs) or human NSCs were injected into five CNS sites in very large numbers (100,000 cells/site, or a total of 500,000 cells) into 18 neonatal mice homozygous for a targeted deletion (knockout) of the acid sphingomyelinase (ASM) gene (called ASMKO mice), a faithful model of human Niemann-Pick type A (NP-A) disease, and into 10 wild-type mice, all on the C57BL/6J background. Injected mice were not immunosuppressed, and all survived to adulthood. Non-injected ASMKO controls had developed widespread neuronal and glial vacuolation and lysosomal accumulation of sphingomyelin and cholesterol when examined histologically at 16 weeks of age. Unlike children with NP-A disease, the ASMKO mice also lose cerebellar Purkinje neurons progressively, are ataxic, and show parallel progressive declines in rotorod performance. At 16 weeks NSC-injected mice showed a dramatic decrease in neuronal and glial vacuolation (by standard histological staining) and in cholesterol accumulation (by filipin fluorescence staining) throughout the cerebral neocortex, hippocampal formation, striatum and cerebellum, with lesser but clear improvement throughout the brainstem. Improvement was modestly but consistently better in human HFT13 injected than in mouse C17.2-injected ASMKO mice. Improvement in the ASMKO brains was more widespread than the distribution of NSCs, an indication that ASM must have been secreted and diffused at therapeutic concentrations beyond the territory occupied by NSCs. However, though Purkinje cell rescue has been achieved with NSCs in some other disease models, loss of Purkinje neurons and decline in rotorod performance were still present in injected ASMKO mice. PMID- 17289005 TI - Spatial distributions of Kv4 channels and KChip2 isoforms in the murine heart based on laser capture microdissection. AB - OBJECTIVE: Regional differences in repolarizing K(+) current densities and expression levels of their molecular components are important for coordinating the pattern of electrical excitation and repolarization of the heart. The small size of hearts from mice may obscure these interventricular and/or transmural expression differences of K(+) channels. We have examined this possibility in adult mouse ventricle using a technology that provides very high spatial resolution of tissue collection. METHODS: Conventional manual dissection and laser capture microdissection (LCM) were utilized to dissect tissue from distinct ventricular regions. RNA was isolated from epicardial, mid-myocardial and endocardial layers of both the right and left ventricles. Real-time RT-PCR was used to quantify the transcript expression in these different regions. RESULTS: LCM revealed significant interventricular and transmural gradients for both Kv4.2 and the alpha-subunit of KChIP2. The expression profile of a second K(+) channel transcript, Kir2.1, which is responsible for the inwardly rectifying K(+) current I(k1), showed no interventricular or transmural gradients and therefore served as a negative control. CONCLUSIONS: Our findings are in contrast to previous reports of a relatively uniform left ventricular transmural pattern of expression of Kv4.2, Kv4.3 and KChIP2 in adult mouse heart, which appear to be different than that in larger mammals. Specifically, our results demonstrate significant epi- to endocardial differences in the patterns of expression of both Kv4.2 and KChIP2. PMID- 17289004 TI - Down-regulation of ERK but not MEK phosphorylation in cultured endothelial cells by repeated changes in cyclic stretch. AB - OBJECTIVE: Effects of cyclic stretch on endothelial cells are studied usually by exposing cells cultured under stretch-free conditions to some levels of cyclic stretch, but in vivo these cells experience both increase and decrease in stretch. Experiments were designed to study how endothelial cells maintained under certain levels of cyclic stretch responded to shifts in stretch frequencies and amplitudes. METHODS: Confluent endothelial cells cultured on flexible silicone membranes with or without pre-stretching for 2-12 h were exposed to various levels of stretch amplitude or frequency and assayed for extracellular signal-regulated kinase 1/2 (ERK) phosphorylation. RESULTS: When endothelial cells without pre-stretching were cyclically stretched, ERK phosphorylation increased, peaking approximately 15 min and slowly decreased. In contrast, when pre-stretched cells were exposed to either higher or lower stretch condition, ERK phosphorylation transiently decreased within 5 min, indicating that some mechanism which down-regulated ERK phosphorylation was activated. Because phosphorylation of ERK kinase (MEK) was not inhibited in these cells, this mechanism targeted ERK directly, not the upstream kinases of the Ras-Raf-MEK-ERK cascade. Furthermore, this ERK down-regulation in pre-stretched cells was not induced by agonists, was inhibited by Na(3)VO(4) but not okadaic acid, and was detected in the cytosolic fraction. Repeated shifts in stretch conditions induced continuous down-regulation of ERK but not MEK phosphorylation. CONCLUSIONS: Endothelial cells are capable of down-regulating ERK phosphorylation in a cyclic stretch- and tyrosine phosphatase-dependent manner. Frequent changes in stretch conditions constitutively activated this ability, which could play some role in regulating ERK activity in endothelial cells in vivo. PMID- 17289006 TI - The KCNQ1 potassium channel is down-regulated by ubiquitylating enzymes of the Nedd4/Nedd4-like family. AB - OBJECTIVE: The voltage-gated KCNQ1 potassium channel regulates key physiological functions in a number of tissues. In the heart, KCNQ1 alpha-subunits assemble with KCNE1 beta-subunits forming a channel complex constituting the delayed rectifier current I(Ks). In epithelia, KCNQ1 channels participate in controlling body electrolyte homeostasis. Several regulatory mechanisms of the KCNQ1 channel complexes have been reported, including protein kinase A (PKA)-phosphorylation and beta-subunit interactions. However, the mechanisms controlling the membrane density of KCNQ1 channels have attracted less attention. METHODS AND RESULTS: Here we demonstrate that KCNQ1 proteins expressed in HEK293 cells are down regulated by Nedd4/Nedd4-like ubiquitin-protein ligases. KCNQ1 and KCNQ1/KCNE1 currents were reduced upon co-expression of Nedd4-2, the isoform among the nine members of the Nedd4/Nedd4-like family displaying the highest expression level in human heart. In vivo expression of a catalytically inactive form of Nedd4-2, able to antagonize endogenous Nedd4-2 in guinea-pig cardiomyocytes, increased I(Ks) significantly, but did not modify I(K1). Concomitant with the reduction in current induced by Nedd4-2, an increased ubiquitylation as well as a decreased total level of KCNQ1 proteins were observed in HEK293 cells. Pull-down and co immunoprecipitation experiments showed that Nedd4-2 interacts with the C-terminal part of KCNQ1. The Nedd4/Nedd4-like-mediated regulation of the KCNQ1 channel complexes is strictly dependent on a PY motif located in the distal part of the C terminal domain. When this motif was mutated, the current and ubiquitylation levels were unaffected by Nedd4-2, and Nedd4-2 proteins were neither pulled-down nor co-immunoprecipitated. CONCLUSIONS: These results suggest that KCNQ1 internalization and stability is physiologically regulated by its Nedd4/Nedd4 like-dependent ubiquitylation. This mechanism may thereby be important in regulating the surface density of the KCNQ1 channels in cardiomyocytes and other cell types. PMID- 17289007 TI - Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats. AB - OBJECTIVE: A reduction of the Ca(2+)-independent transient outward potassium current (I(to)) in epicardial but not in endocardial myocytes of the left ventricle has been observed in cardiac hypertrophy and is thought to contribute to the electrical vulnerability associated with this pathology. METHODS: In the present study we investigated the molecular mechanisms underlying regional alterations in I(to) in hypertrophied hearts of spontaneously hypertensive rats (SHR) using the whole-cell patch-clamp technique, quantitative RT-PCR and heterologous expression of underlying ion channel subunits. RESULTS: I(to) was significantly smaller in epicardial myocytes of SHR than in Wistar-Kyoto (WKY) controls (11.1+/-0.9 pA/pF, n=20 vs. 16.8+/-1.7 pA/pF, n=20, p<0.01), but not different in endocardial myocytes from both groups. Quantitative RT-PCR analysis of the genes encoding I(to) revealed significantly lower levels of Kv4.2 and Kv4.3 mRNA in the epicardial region of SHR rats compared to WKY rats. In contrast, mRNA expression levels of all three splice variants of the beta-subunit KChIP2 were significantly higher in both endo- and epicardial myocytes from SHR than from WKY rats. In parallel, inactivation of I(to), which is negatively modulated by KChIP2, was slowed down in SHR while recovery from inactivation remained unchanged. Heterologous co-expression of increasing amounts of KChIP2b together with a fixed amount of Kv4.2 in Xenopus laevis oocytes revealed a hyperbolic relation of recovery from inactivation and inactivation time constant, demonstrating that KChIP2 preferentially affects inactivation, if its expression level is high. CONCLUSION: These results suggest that downregulation of I(to) in the left ventricle of SHR is mediated by a reduced expression of Kv4.2 and Kv4.3 (but not of KChIP2), whereas the slower inactivation of I(to) can be explained by increased expression levels of KChIP2 in SHR. PMID- 17289008 TI - Effect of Cassia fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats. AB - The hepatoprotective and antioxidant effect of Cassia fistula Linn. leaf extract on liver injury induced by diethylnitrosamine (DEN) was investigated. Wistar rats weighing 200+/-10g were administered a single dose of DEN (200mg/kg b.w., i.p.) and left for 30 days. For hepatoprotective studies, ethanolic leaf extract (ELE) of C. fistula Linn. (500mg/kg b.w., p.o.) was administered daily for 30 days. AST, ALT, ALP, LDH, gamma-GT and bilirubin were estimated in serum and liver tissue. Lipid peroxidation (LPO), SOD and CAT were also estimated in liver tissue as markers of oxidative stress. DEN induced hepatotoxicity in all the treated animals were evident by elevated serum ALT, AST, ALP and bilirubin levels and a simultaneous fall in their levels in the liver tissue after 30 days. Induction of oxidative stress in the liver was evidenced by increased LPO and fall in the activities of SOD and CAT. ELE administration for 30 days prevented the DEN induced hepatic injury and oxidative stress. In conclusion, it was observed that ELE of C. fistula Linn. protects the liver against DEN induced hepatic injury in rats. PMID- 17289009 TI - Different mechanisms involved in apoptosis following exposure to benzo[a]pyrene in F258 and Hepa1c1c7 cells. AB - The present study compares and elucidates possible mechanisms why B[a]P induces different cell signals and triggers apparently different apoptotic pathways in two rather similar cell lines (hepatic epithelial cells of rodents). The rate and maximal capacity of metabolic activation, as measured by the formation of B[a]P tetrols and B[a]P-DNA adducts, was much higher in mouse hepatoma Hepa1c1c7 cells than in rat liver epithelial F258 cells due to a higher induced level of cyp1a1. B[a]P increased intracellular pH in both cell lines, but this change modulated the apoptotic process only in F258 cells. In Hepa1c1c7 cells reactive oxygen species (ROS) production appeared to be a consequence of toxicity, unlike F258 cells in which it was an initial event. The increased mitochondrial membrane potential found in F258 cells was not observed in Hepa1c1c7 cells. Surprisingly, F258 cells cultured at low cell density were somewhat more sensitive to low (50nM) B[a]P concentrations than Hepa1c1c7 cells. This could be explained partly by metabolic differences at low B[a]P concentrations. In contrast to the Hepa1c1c7 model, no activation of cell survival signals including p-Akt, p-ERK1/2 and no clear inactivation of pro-apoptotic Bad was observed in the F258 model following exposure to B[a]P. Another important difference between the two cell lines was related to the role of Bax and cytochrome c. In Hepa1c1c7 cells, B[a]P exposure resulted in a "classical" translocation of Bax to the mitochondria and release of cytochrome c, whereas in F258 cells no intracellular translocation of these two proteins was seen. These results suggest that the rate of metabolism of B[a]P and type of reactive metabolites formed influence the resulting balance of pro-apoptotic and anti-apoptotic cell signaling, and hence the mechanisms involved in cell death and the chances of more permanent genetic damage. PMID- 17289010 TI - Analysis of human bone alkaline phosphatase isoforms: comparison of isoelectric focusing and ion-exchange high-performance liquid chromatography. AB - BACKGROUND: Several isoforms of alkaline phosphatase (ALP) can be identified in human tissues and serum after separation by anion-exchange HPLC and isoelectric focusing (IEF). METHODS: We purified four soluble bone ALP (BALP) isoforms (B/I, B1x, B1 and B2) from human SaOS-2 cells, determined their specific pI values by broad range IEF (pH 3.5-9.5), compared these with commercial preparations of bone, intestinal and liver ALPs and established the effects of neuraminidase and wheat germ lectin (WGA) on enzyme activity. RESULTS: Whilst the isoforms B1x (pI=4.48), B1 (pI=4.32) and B2 (pI=4.12) resolved as well-defined bands, B/I resolved as a complex (pI=4.85-6.84). Neuraminidase altered the migration of all BALP isoforms to pI=6.84 and abolished their binding to the anion-exchange matrix, but increased their enzymatic activities by 11-20%. WGA precipitated the BALP isoforms in IEF gels and the HPLC column and attenuated their enzymatic activities by 54-73%. IEF resolved the commercial BALP into 2 major bands (pI=4.41 and 4.55). CONCLUSIONS: Migration of BALP isoforms is similar in IEF and anion-exchange HPLC and dependent on sialic acid content. HPLC is preferable in smaller scale research applications where samples containing mixtures of BALP isoforms are analysed. Circulating liver ALP (pI=3.85) can be resolved from BALP by either method. IEF represents a simpler approach for routine purposes even though some overlapping of the isoforms may occur. PMID- 17289011 TI - Maternal serum C-reactive protein concentrations in early pregnancy and subsequent risk of preterm delivery. AB - OBJECTIVE: To examine the relation between maternal early pregnancy serum C reactive protein (CRP) and preterm delivery (PTD). DESIGN AND METHODS: Women were recruited before 20 weeks gestation and were followed up until delivery. Maternal serum CRP was measured by competitive immunoassay. Logistic regression procedures were used to calculate adjusted odds ratio (OR) and 95% confidence intervals (95%CI). RESULTS: Elevations in CRP concentrations were associated with the risk of PTD overall. After adjusting for confounding, the OR for highest quartile (> or = 7.5 vs. < 2.0 mg/L) of CRP was 2.04 (95%CI: 1.13-3.69). Stratified analyses indicated that elevated CRP was associated with an increased risk of spontaneous preterm labour (OR=2.15, 95%CI: 0.85-5.42), medically indicated preterm delivery (OR=3.29, 95%CI: 0.98-11.02), and very preterm delivery (OR=20.6, 95%CI: 2.53 168.03), but not with preterm premature rupture of membranes (OR=1.48, 95%CI: 0.56-3.86). CONCLUSIONS: Elevated CRP concentrations in early pregnancy are associated with an increased risk of PTD, particularly medically indicated PTD and very PTD. PMID- 17289012 TI - Iron-dependent vs. iron-independent cold-induced injury to cultured rat hepatocytes: a comparative study in physiological media and organ preservation solutions. AB - We previously described the entity of cold-induced apoptosis to rat hepatocytes and characterized its major, iron-dependent pathway. However, after cold incubation in some solutions, e.g. cell culture medium, hepatocytes show an additional, yet uncharacterized component of cold-induced injury. We here assessed the effects of organ preservation solutions on both components of cold induced injury and tried to further characterize the iron-independent component. None of the preservation solutions (University of Wisconsin, histidine-tryptophan ketoglutarate, Euro-Collins, histidine-lactobionate, sodium-lactobionate-sucrose and Celsior solutions) provided significant protection against cold-induced cell injury (LDH release after 24-h cold incubation/3h rewarming >65% for all solutions); three solutions even enhanced cold-induced injury. However, when the predominant iron-dependent mechanism was eliminated by the addition of iron chelators, all preservation solutions yielded hepatocyte protection that was clearly superior to the one obtainable in cell culture medium or Krebs-Henseleit buffer with iron chelators (LDH release after 24-h cold incubation/3h rewarming 0.98, p<0.0001). The fully automated headspace trap procedure requires only minimal sample preparation and is easy to apply. PMID- 17289059 TI - Supercritical fluid extraction of quinolizidine alkaloids from Sophora flavescens Ait. and purification by high-speed counter-current chromatography. AB - Supercritical fluid extraction (SFE) was used to extract quinolizidine alkaloids from Sophora flavescens Ait. (Kushen). An orthogonal test L(9)(3)(4) including pressure, temperature, flow rate of CO(2) and the amount of modifier was performed to get the optimal conditions. The process was then scaled up by 30 times with a preparative SFE system under 25 MPa, 50 degrees C and a flow rate of CO(2) (2l/min) and the amount of modifier (0.04 ml/min). The crude extracts were separated and purified by high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of chloroform-methanol-2.3 x 10(-2)M NaH(2)PO(4) (27.5:20:12.5, v/v), and the collected fractions were analyzed by high-performance liquid chromatography (HPLC). Three kinds of quinolizidine alkaloids were obtained, yielding 10.02 mg of matrine, 22.07 mg of oxysophocarpine and 79.93 mg of oxymatrine with purities of 95.6, 95.8, 99.6% in one-step separation, respectively. PMID- 17289060 TI - Simultaneous determination of anthraquinones in rhubarb by high-performance liquid chromatography and capillary electrophoresis. AB - High-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) were compared to simultaneously determine and separate 11 anthraquinones from rhubarb, including emodin, chrysophanol, rhein and their glucosides, aloe-emodin, sennoside A, and sennoside B. A UV-diode array detector (DAD) at 254 nm with a gradient elution of acetonitrile/water (method A: 0 min 6:94, 12 min 12:88, 15 min 20:80, 40 min 25:75, 53 min 55:45, 55 min 100:0; method B: 0 min 5:95, 2 min 15:85, 5 min 20:80, 12 min 25:75, 15 min 50:50, 19 min 98:2) at 28(+/-1) degrees C (method A) and 30-60 degrees C (method B) in HPLC or with 0.03 M borate buffer (pH 10.0) containing 25% (v/v) acetonitrile with 0.002 M 2,6-di-O-methyl-beta cyclodextrin (CD) and 0.005 M alpha-CD in CE effectively detected this separation in 25 min. The detection limits of anthraquinones from rhubarb were in the 0.02 0.2 microg/mL and 0.1-0.8 microg/mL ranges for HPLC and CE, respectively. The established HPLC and CE methods are suitable for quantitative determination of emodin, chrysophanol, aloe-emodin, emodin-1-beta-d-glucoside, emodin-8-beta-d glucoside, chrysophanol-1-beta-d-glucoside, chrysophanol-8-beta-d-glucoside, and rhein-8-beta-d-glucoside. PMID- 17289061 TI - Protein separation and enrichment by counter-current chromatography using reverse micelle solvent systems. AB - A protein mixture consisting of myoglobin, cytochrome c, and lysozyme was separated by high-speed counter-current chromatography using a two-phase aqueous/reverse micelle-containing organic solvent system. About 50% stationary phase retention ratio was obtained in most chromatographic experiments. Separations were manipulated mainly by pH gradients that controlled the electrostatic interactions between the protein molecules and reverse micelles. Separations were further improved by incorporating an ionic strength gradient along with the pH gradient. Control of ionic strength in the aqueous solution helped fine-tune protein partitioning between the stationary and mobile phases. Although non-specific protein interactions affected baseline resolution, recovery of cytochrome c and lysozyme reached 90% and 82%. Furthermore, concentration or enrichment of these two proteins was achieved from a large-volume sample load. This technique can potentially be employed in the recovery and enrichment of proteins from large-volume aqueous solutions. PMID- 17289062 TI - On the use of solid phase ion exchangers for isolation of amino acids from liquid samples and their enantioselective gas chromatographic analysis. AB - This work focuses on the development of a suitable working procedure for preconcentration of amino acids enantiomers from water samples using a solid phase extraction. The three types of ion exchangers with various capabilities have been used. The effect of experimental conditions in SPE procedure employing strong anion exchange (SAX), weak (WCX) and strong cation exchange (SCX) cartridges (such as sample volume, pH, origin of elution solvent and its volume) on effective preconcentration of the model set of amino acids has been studied in detail. The enantiomers of isolated and preconcentrated amino acids have been analysed by GC on three capillary columns coated with chiral selectors. The different amino acids derivatives have been investigated in order to achieve optimal resolution of biogenic amino acids and their enantiomers. The best separation of amino acid enantiomers has been obtained on a Chirasil-L-Val column analysing their N-TFA methyl esters. It has been shown that SCX-SPE cartridge with sulfonic groups attached on silicagel support is most suitable for isolation and preconcentration of amino acids from water samples. For this sample treatment procedure, the overall recovery of extraction process has been calculated as an average value from three measurements. It has been found, that recoveries are practically identical for both enantiomers of a particular amino acid and varies in the range 75-99% depending on the type of amino acid. The effectivity of this sample preparation and GC method has been verified by preconcentration of amino acids from orange juice fortified by racemic mixture of some selected amino acids. PMID- 17289063 TI - Separation of Liquiritin by simulated moving bed chromatography. AB - Liquiritin was extracted from the natural product Licorice, and then purified using a three-zone simulated moving bed set up in our laboratory, with a C(18) bonded silica as the stationary phase and an aqueous solution of ethanol as the mobile phase. The isotherm parameters of Liquiritin and of the only closely eluting impurity were obtained using the inverse method, fitting the experimental elution profiles to calculated elution profiles, assuming a binary Langmuir isotherm model as an approximation. The operating parameters of the simulated moving bed were selected according to the Equilibrium Theory. This allowed the preparation of 85% pure Liquiritin. Finally, 99% pure Liquiritin was obtained through a last step of recrystallization. PMID- 17289064 TI - Gas chromatographic-mass spectrometric fragmentation study of flavonoids as their trimethylsilyl derivatives: analysis of flavonoids, sugars, carboxylic and amino acids in model systems and in citrus fruits. AB - The fragmentation patterns and quantitation possibilities of three anthocyanidins (pelargonidin, cyanidin, malvidin), one flavonol (quercetin), two flavones (apigenin, luteolin) and two flavanones (naringenin, hesperetin) have been investigated as trimethylsilyl and as trimethylsilyl (oxime) derivatives by gas chromatography-mass spectrometry. Results proved that anthocyanidins and flavanones form trimethylsilyl (oximes), while flavonol and flavones provide simple trimethylsilyl derivatives. In all cases, characteristic fragments of high masses are formed proper for quantitation purposes. Hydrolysis conditions for naringin, hesperidin and rutin have been optimized, resulting in the quantitative release of naringenin, hesperetin and quercetin together with their corresponding saccharides. These basic studies made possible the identification and quantification of the flavonoid, carboxylic-/amino acid and sugar constituents of citrus fruit juices and albedos, without any extraction/enrichment procedure. In total 33 compounds have been determined in hydrolyzed samples, such as 2 flavonoids (naringenin and hesperetin), 6 phenolic acids (trimethoxybenzoic, 4 hydroxybenzoic, vanillic, quinic, chlorogenic and rosmarinic acids), 3 aliphatic carboxylic acids (levulinic, malic, citric acids), phosphoric acid, 4 amino acids (aspartic, glutamic acids, alanine, proline), 9 monosaccharides (xylose, arabinose, rhamnose, fucose, fructose, galactose, glucose, galacturonic acid, sedoheptulose), inositol, sugarphosphate, 5 disaccharides and tocopherol. Measurements were carried out as the trimethylsilyl (oxime) ether/ester derivatives of constituents, in the concentration range of 2 x 10(-3) to 49.9%. Identification level of samples varied between 26.4 and 77.5%, expressed in dry matter content of juices and albedos. PMID- 17289065 TI - Ground, sieved, and C18 modified monolithic silica particles for packing material of microcolumn high-performance liquid chromatography. AB - We here report a new type of stationary phase for microcolumns. C18 modified silica monolith particles were prepared by grinding and sieving the silica monolith followed by C18 modification and end-capping, and were used as packing material. Ground silica monolith particles were not spherical but irregular with some residual monolithic network structure. The separation efficiency of the stationary phase made of sieved monolith particles (5-10 microm) was better than that of the stationary phase made of unsieved particles. The microcolumn packed with the sieved C18 ground monolith particles (5-10 microm) showed quite good separation efficiency (height equivalent to theoretical plate, HETP, as low as 15 microm) and it was even superior to the microcolumn packed with a commercial spherical 5 microm C18 stationary phase. The column pressure drop of C18 monolith particles was about two-third of that of the commercial spherical C18 phase. The preparation method of C18 stationary phase with ground and sieved silica monolith particles presumably suggests advantages of simplicity and convenience in modification and washing procedures compared to bulk silica monolith. It also showed both improved separation efficiency and low back pressure. PMID- 17289066 TI - Comparison of general rate model with a new model--artificial neural network model in describing chromatographic kinetics of solanesol adsorption in packed column by macroporous resins. AB - Herein, two models, the general rate model taking into account convection, axial dispersion, external and intra-particle mass transfer resistances and particle size distribution (PSD) and the artificial neural network model (ANN) were developed to describe solanesol adsorption process in packed column using macroporous resins. First, Static equilibrium experiments and kinetic experiments in packed column were carried out respectively to obtain experimental data. By fitting static experimental data, Langmuir isotherm and Freundlich isotherm were estimated, and the former one was used in simulation coupled with general rate model considering better correlative coefficients. The simulated results showed that theoretical predictions of general rate model with PSD were well consistent with experimental data. Then, a new model, the ANN model, was developed to describe present adsorption process in packed column. The encouraging simulated results showed that ANN model could describe present system even better than general rate model. At last, by using the predictive ability of ANN model, the influence of each experimental parameter was investigated. Predicted results showed that with the increases of particle porosity and the ratio of bed height to inner column diameter (ROHD), the breakthrough time was delayed. On the contrary, an increase in feed concentration, flow rate, mean particle diameter and bed porosity decreased the breakthrough time. PMID- 17289067 TI - Aggregation behavior of polypropylene oxide end-capped by positive charges. AB - We investigated the aggregation behavior of poly(propylene oxide) with positive charges at both ends in aqueous solution by means of solution turbidity, dynamic light-scattering, solubilization of fluorescence probe, and optical microscopic observation. The positive charges were produced by protonation of terminal NH2 groups attached to the polymer composed of 33 PO units. It was found that the polymer exists as unimers at low temperature and as micelles at high temperature, whereas at intermediate temperature, there appear different aggregation states depending on the polymer concentration; i.e., 100-nm size aggregates which might be vesicles, 1-microm size particles (oil droplets), and a certain turbid phase showing a characteristic texture under optical microscopic observation. Filtration experiments to remove the oil droplets showed that the insoluble components with less hydrophilic property included in the polymer sample are responsible for the formation of oil droplets. Comparison of the phase diagrams obtained for the polymer/H2O mixtures before and after the filtration treatment suggests that the formation of 100 nm size aggregates and some unidentified phase in between unimer and micellar regions is an intrinsic property of the poly(propyrene oxide) chain end-capped by electrical charges. PMID- 17289068 TI - Controllable preparation of magnetic polymer microspheres with different morphologies by miniemulsion polymerization. AB - Magnetic poly(styrene-co-acrylic acid-co-acrylamide) microspheres were prepared by water-in-oil-in-water (W/O/W) miniemulsion polymerization of monomers in the presence of Fe3O4 nanoparticles. The copolymerizable monomers of acrylic acid and acrylamide were used not only to modify the surfaces of the microspheres with functional groups, but also to act as viscosity regulators to control the morphology and size of these microspheres. It was experimentally observed that the surfaces of these microspheres were functionalized with NH2 groups produced by copolymerization, the morphologies (sphere, ringlike, and one-hole) of the microspheres were controlled by the concentration of copolymerizable monomers, and all samples prepared were superparamagnetic. The possible mechanism of formation of these magnetic microspheres is also discussed. PMID- 17289069 TI - Direct synthesis of fct-structured FePt nanoparticles at low temperature with assistance of poly(N-vinyl-2-pyrrolidone). AB - Direct synthesis of fct-structured FePt nanoparticles was successfully achieved by using poly(N-vinyl-2-pyrrolidone) as a protective reagent at lower temperature than the case using low molecular weight ligands as a protective reagent. Experimental data suggest that a transformation of FePt nanoparticles from face centered cubic to face-centered tetragonal (fct) structure takes place at reaction temperature of 261 degrees C. The results of XRD and the magnetic properties exhibit that the FePt nanoparticles synthesized at 261 degrees C have partially ordered fct-structure and a ferromagnetic behavior at room temperature. PMID- 17289070 TI - A new standardized lipolysis approach for characterization of emulsions and dispersions. AB - A new standardized lipolysis approach is presented where the focus is on the initial rate of lipolysis. An advantage is that data obtained in this way reflect degradation before growing amounts of lipolysis products retard the process. The method can be used to rank different lipase substrates. In particular, the method can be used to obtain information about the susceptibility to degradation of various emulsions and dispersions that are used in technical applications. We present how the method is standardized to facilitate comparison of various substrates. This involves (i) lipase substrate in excess, i.e., the amount of lipase is rate limiting, and (ii) expressing rate of degradation relative to that of a reference substrate, tributyrin. Under such conditions, with the amount of lipase substrate held constant, an increase in enzymatic activity will generate a proportional increase in the lipolysis rate. This enables comparison of results obtained from different enzyme batches and corrects for day-to-day variability. Examples illustrating the potential of the method to discriminate and rank different lipase substrates with regard to enzymatic degradation are presented. PMID- 17289072 TI - Quantitative analysis of eosinophil chemotaxis tracked using a novel optical device -- TAXIScan. AB - We have reported previously the development of an optically accessible, horizontal chemotaxis apparatus, in which migration of cells in the channel from a start line can be traced with time-lapse intervals using a CCD camera (JIM 282, 1-11, 2003). To obtain statistical data of migrating cells, we have developed quantitative methods to calculate various parameters in the process of chemotaxis, employing human eosinophil and CXCL12 as a model cell and a model chemoattractant, respectively. Median values of velocity and directionality of each cell within an experimental period could be calculated from the migratory pathway data obtained from time-lapse images and the data were expressed as Velocity-Directionality (VD) plot. This plot is useful for quantitatively analyzing multiple migrating cells exposed to a certain chemoattractant, and can distinguish chemotaxis from random migration. Moreover precise observation of cell migration revealed that each cell had a different lag period before starting chemotaxis, indicating variation in cell sensitivity to the chemoattractant. Thus lag time of each cell before migration, and time course of increment of the migrating cell ratio at the early stages could be calculated. We also graphed decrement of still moving cell ratio at the later stages by calculating the duration time of cell migration of each cell. These graphs could distinguish different motion patterns of chemotaxis of eosinophils, in response to a range of chemoattractants; PGD(2), fMLP, CCL3, CCL5 and CXCL12. Finally, we compared parameters of eosinophils from normal volunteers, allergy patients and asthma patients and found significant difference in response to PGD(2). The quantitative methods described here could be applicable to image data obtained with any combination of cells and chemoattractants and useful not only for basic studies of chemotaxis but also for diagnosis and for drug screening. PMID- 17289071 TI - Hereditary long QT syndrome due to autoimmune hypoparathyroidism in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. AB - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type I, is a rare autosomal recessively inherited disorder characterized by variable combinations of endocrine and nonendocrine symptoms. In this report, we describe two 20- and 17 year-old Turkish siblings presenting with typical symptoms of APECED, including Addison disease, alopecia, vitiligo, and hypopituitarism, in whom electrocardiographic examinations demonstrated an abnormal prolongation of the QT interval. In both cases, excessive hypocalcemia due to primary hypoparathyroidism was identified as the underlying cause of the long QT syndrome. Sequencing the gene coding for the autoimmune regulator revealed a homozygous missense mutation in exon 14 with a C-to-T transition that resulted in the substitution of proline 539 for leucine in the carboxy-terminal protein molecule. Our data show that a single point mutation in the transcriptional active autoimmune regulator protein is associated with inherited alterations in calcium metabolism resulting from autoimmune reactions against the parathyroid glands. This finding defines a congenital autoimmune disease as a hereditary long QT syndrome. PMID- 17289073 TI - The promiscuous nature of the cardiac sodium current. AB - Voltage-gated sodium channels (Na(V)s) are essential in propagating neuronal electrical impulse and triggering muscle contraction. In the heart, the Na(+) channel isoform Na(V)1.5 is strongly expressed and in the past was thought to be solely responsible for generating the cardiac Na(+) current (I(Na)). Recent studies, however, revealed that neuronal and skeletal muscle Na(+) channel isoforms are also expressed in the heart and contribute to cardiac I(Na). Amongst the findings is that many neuronal type Na(V)s are expressed in specific areas of the conduction system and ventricles. The contribution of these TTX-sensitive channels to normal cardiac function remains unclear but these data raise the possibility of a more prominent role of TTX-sensitive channels in conduction. Moreover, cardiac arrhythmias are commonly observed in many neuronal and musculoskeletal diseases despite their exclusive linkage to mutations in the neuronal and skeletal muscle sodium channel isoforms. The cause for these arrhythmias remains poorly understood. These recent findings indicate that neuronal and skeletal muscle sodium channels are expressed in areas of the heart that may be involved in the clinical phenotypes observed. The purpose of this review is to give an overview of the evidence for the presence of TTX-sensitive Na(V) isoforms in the heart and present the hypothesis brought forward so far for their direct role in cardiac function. These data demonstrate the promiscuous nature of the cardiac sodium current at the molecular level and should help us to bridge the gap that exists between our understanding of cardiac physiology and arrhythmias associated to brain and myotonic diseases. PMID- 17289074 TI - Crystal structure of the Anabaena sensory rhodopsin transducer. AB - We present crystal structures of the Anabaena sensory rhodopsin transducer (ASRT), a soluble cytoplasmic protein that interacts with the first structurally characterized eubacterial retinylidene photoreceptor Anabaena sensory rhodopsin (ASR). Four crystal structures of ASRT from three different spacegroups were obtained, in all of which ASRT is present as a planar (C4) tetramer, consistent with our characterization of ASRT as a tetramer in solution. The ASRT tetramer is tightly packed, with large interfaces where the well-structured beta-sandwich portion of the monomers provides the bulk of the tetramer-forming interactions, and forms a flat, stable surface on one side of the tetramer (the beta-face). Only one of our four different ASRT crystals reveals a C-terminal alpha-helix in the otherwise all-beta protein, together with a large loop from each monomer on the opposite face of the tetramer (the alpha-face), which is flexible and largely disordered in the other three crystal forms. Gel-filtration chromatography demonstrated that ASRT forms stable tetramers in solution and isothermal microcalorimetry showed that the ASRT tetramer binds to ASR with a stoichiometry of one ASRT tetramer per one ASR photoreceptor with a K(d) of 8 microM in the highest affinity measurements. Possible mechanisms for the interaction of this transducer tetramer with the ASR photoreceptor via its flexible alpha-face to mediate transduction of the light signal are discussed. PMID- 17289075 TI - Visualization of functional rotor proteins of the bacterial flagellar motor in the cell membrane. AB - The bacterial flagellar motor is a rotary motor driven by the electrochemical potentials of specific ions across the cell membrane. Direct interactions between the rotor protein FliG and the stator protein MotA are thought to generate the rotational torque. Here, we used total internal reflection fluorescent microscopy to observe the localization of green fluorescent protein (GFP)-fused FliG in Escherichia coli cells. We identified three types of fluorescent punctate signals: immobile dots, mobile dots that exhibited simple diffusion, and mobile dots that exhibited restricted diffusion. When GFP-FliG was expressed in a DeltafliG background, most of the cells were not mobile. When the cells were tethered to a glass side, however, rotating cells were commonly observed and a single fluorescent dot was always observed at the rotational center of the tethered cell. These fluorescent dots were likely positions at which functional GFP-FliG had been incorporated into a flagellar motor. Our results suggest that flagellar basal bodies diffuse in the cytoplasmic membrane until the axial structure and/or other structures assemble. PMID- 17289076 TI - Loading a ring: structure of the Bacillus subtilis DnaB protein, a co-loader of the replicative helicase. AB - Loading of the ring-shaped replicative helicase is a critical step in the initiation of DNA replication. Bacillus subtilis has adopted a two-protein strategy to load its hexameric replicative helicase: DnaB and DnaI interact with the helicase and mediate its delivery onto DNA. We present here the 3D electron microscopy structure of the DnaB protein, along with a detailed analysis of both its oligomeric state and its domain organization. DnaB is organized as an asymmetric tetramer that is comprised of two stacked components, one arranged as a closed collar and the other as an open sigma shape. Intriguingly, the 3D map of DnaB exhibits an overall architecture similar to the structure of the Escherichia coli gamma-complex, the loader of the ring-shaped processivity factor. We propose a model whereby each DnaB monomer participates in both stacked components of the tetramer and displays a different overall shape. This asymmetric quaternary organization could be a general feature of ring loaders. PMID- 17289078 TI - Evolution of programmable zinc finger-recombinases with activity in human cells. AB - Site-specific recombinases are important tools for genomic engineering in many living systems. Applications of recombinases are, however, constrained by the DNA targeting endemic of the recombinase used. A tremendous range of recombinase applications can be envisioned if the targeting of recombinase specificity can be made readily programmable. To address this problem we sought to generate zinc finger-recombinase fusion proteins (Rec(ZF)s) capable of site-specific function in a diversity of genetic contexts. Our first Rec(ZF), Tn3Ch15(X2), recombined substrates derived from the native Tn3 resolvase recombination site. Substrate Linked Protein Evolution (SLiPE) was used to optimize the catalytic domains of the enzymes Hin, Gin, and Tn3 for resolution between non-homologous sites. One of the evolved clones, GinL7C7, catalyzed efficient, site-specific recombination in a variety of sequence contexts. When introduced into human cells by retroviral transduction, GinL7C7 excised a 1.4 kb EGFP cassette out of the genome, diminishing fluorescence in approximately 17% of transduced cells. Following this template of rational design and directed evolution, Rec(ZF)s may eventually mediate gene therapies, facilitate the genetic manipulation of model organisms and cells, and mature into powerful new tools for molecular biology and medicine. PMID- 17289079 TI - Lorentzian model of roots for understory yellow birch and sugar maple saplings. AB - Total 66 small (<50m(2)), 24 medium (101-200m(2)) and 36 large (201-500m(2)) canopy gaps at the three sites of yellow birch (Betula alleghaniensis Britton) and sugar maple (Acer saccharum Marsh) forests were established in southern Quebec, Canada. Half of the gaps were covered by 8x8m(2) shading cloths to mimic a closed canopy. From these gaps, 46 understory yellow birch and 46 sugar maple saplings with different tree ages and sizes were sampled. Single- and multi variable linear and nonlinear models of root biomass and traits (root surface area, volume, length and endings) were developed and examined. Lorentzian model as a multi-variable nonlinear model was firstly applied to the simulations using both base diameter and height, and performed the best fit to total root biomass in both species with the highest correlation coefficients (R(2)=0.96 and 0.98) and smallest root mean squared deviations (RMSD=7.85 and 7.02) among all the examined models. The model also accurately simulated small fine root (2.0mm in diameter), coarse fine root (>2.0-5.0mm) and coarse root (>5.0mm) biomass (R(2)=0.87-0.99; RMSD=2.24-6.41), and the root traits (R(2)=0.71-0.99; RMSD=0.19 19.38). The study showed yellow birch roots were longer, larger, had more endings (tips) and grew faster than sugar maple roots. The root traits were largely distributed to small fine roots, sharply decreased from small fine roots to coarse fine roots, the fewest in coarse roots except for root volume. When trees were large, coarse root biomass increased more rapidly than fine root biomass, but vise versa when the trees were small. PMID- 17289080 TI - Cancer onset and progression: a genome-wide, nonlinear dynamical systems perspective on onconetworks. AB - It is hypothesized that the many human cell types corresponding to multiple states is supported by an underlying nonlinear dynamical system (NDS) of transcriptional regulatory network (TRN) processes. This hypothesis is validated for epithelial cells whose TRN is found to support an extremely complex array of states that we term a "bifurcation nexus", for which we introduce a quantitative measure of complexity. The TRN used is constructed and analyzed by integrating a database of TRN information, cDNA microarray data analyzers, bioinformatics modules, a transcription/translation/post-translation kinetic model, and NDS analysis software. Results of this genome-wide approach suggest that a cell can be induced to persist in one state or to transition between distinct states; apparently irreversible transitions can be reversed when the high dimensional space of extracellular and intracellular parameters is understood. As conditions change, certain cellular states (cell lines) are no longer supported, new ones emerge, and transitions (cell differentiation or death) occur. The accumulation of simulated point mutations (minor changes which individually are insignificant) lead to occasional dramatic transitions. The genome-wide scope of many of these transitions is shown to arise from the cross-linked TRN structure. These notions imply that studying individual oncogenes may not be sufficient to understand cancer; rather, "onconetworks" (subsets of strongly coupled genes supporting multiple cell states) should be considered. Our approach reveals several epithelial onconetworks, each involving oncogenes and anti-tumor and supporting genes. PMID- 17289077 TI - Developmental regulators containing the I-mfa domain interact with T cyclins and Tat and modulate transcription. AB - Positive transcription elongation factor b (P-TEFb) complexes, composed of cyclin dependent kinase 9 (CDK9) and cyclin T1 or T2, are engaged by many cellular transcription regulators that activate or inhibit transcription from specific promoters. The related I-mfa (inhibitor of MyoD family a) and HIC (human I-mfa domain-containing) proteins function in myogenic differentiation and embryonic development by participating in the Wnt signaling pathway. We report that I-mfa is a novel regulator of P-TEFb. Both HIC and I-mfa interact through their homologous I-mfa domains with cyclin T1 and T2 at two binding sites. One site is the regulatory histidine-rich domain that interacts with CDK9 substrates including RNA polymerase II. The second site contains a lysine and arginine-rich motif that is highly conserved between the two T cyclins. This site overlaps and includes the previously identified Tat/TAR recognition motif of cyclin T1 required for activation of human immunodeficiency virus type 1 (HIV-1) transcription. HIC and I-mfa can serve as substrates for P-TEFb. Their I-mfa domains also bind the activation domain of HIV-1 Tat and inhibit Tat- and P-TEFb dependent transcription from the HIV-1 promoter. This transcriptional repression is cell-type specific and can operate via Tat and cyclin T1. Genomic and sequence comparisons indicate that the I-mf and HIC genes, as well as flanking genes, diverged from a duplicated chromosomal region. Our findings link I-mfa and HIC to viral replication, and suggest that P-TEFb is modulated in the Wnt signaling pathway. PMID- 17289081 TI - A mathematical model of breast cancer development, local treatment and recurrence. AB - Cancer development is a stepwise process through which normal somatic cells acquire mutations which enable them to escape their normal function in the tissue and become self-sufficient in survival. The number of mutations depends on the patient's age, genetic susceptibility and on the exposure of the patient to carcinogens throughout their life. It is believed that in every malignancy 4-6 crucial similar mutations have to occur on cancer-related genes. These genes are classified as oncogenes and tumour suppressor genes (TSGs) which gain or lose their function respectively, after they have received one mutative hit or both of their alleles have been knocked out. With the acquisition of each of the necessary mutations the transformed cell gains a selective advantage over normal cells, and the mutation will spread throughout the tissue via clonal expansion. We present a simplified model of this mutation and expansion process, in which we assume that the loss of two TSGs is sufficient to give rise to a cancer. Our mathematical model of the stepwise development of breast cancer verifies the idea that the normal mutation rate in genes is only sufficient to give rise to a tumour within a clinically observable time if a high number of breast stem cells and TSGs exist or genetic instability is involved as a driving force of the mutation pathway. Furthermore, our model shows that if a mutation occurred in stem cells pre-puberty, and formed a field of cells with this mutation through clonal formation of the breast, it is most likely that a tumour will arise from within this area. We then apply different treatment strategies, namely surgery and adjuvant external beam radiotherapy and targeted intraoperative radiotherapy (TARGIT) and use the model to identify different sources of local recurrence and analyse their prevention. PMID- 17289082 TI - Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia. AB - Delta(9)-tetrahydrocannabinol (Delta(9)-THC), a primary psychoactive constituent of cannabis, has been reported to act as a neuroprotectant via the cannabinoid CB(1) receptor. In this study, Delta(9)-THC significantly decreased the infarct volume in a 4 h mouse middle cerebral artery occlusion mouse model. The neuroprotective effect of Delta(9)-THC was completely abolished by SR141716, cannabinoid CB(1) receptor antagonist, and by warming the animals to 31 degrees C. Delta(9)-THC significantly decreased the rectal temperature, and the hypothermic effect was also inhibited by SR141716 and by warming to 31 degrees C. At 24 h after cerebral ischemia, Delta(9)-THC significantly increased the expression level of CB(1) receptor in both the striatum and cortex, but not in the hypothalamus. Warming to 31 degrees C during 4 h cerebral ischemia did not increase the expression of CB(1) receptor at the striatum and cortex in MCA occluded mice. These results show that the neuroprotective effect of Delta(9)-THC is mediated by a temperature-dependent mechanism via the CB(1) receptor. In addition, warming to 31 degrees C might attenuate both the neuroprotective and hypothermic effects of Delta(9)-THC through inhibiting the increase in CB(1) receptor in both the striatum and cortex but not in the hypothalamus, which may suggest a new thermoregulation mechanism of Delta(9)-THC. PMID- 17289083 TI - Extensive expression of markers for acetylcholine synthesis and of M2 receptors in tenocytes in therapy-resistant chronic painful patellar tendon tendinosis - a pilot study. AB - We have recently obtained evidence favoring the occurrence of an up-regulation of a non-neuronal cholinergic system in chronic painful patellar tendon tendinosis. It seems possible that this up-regulation to a certain degree may be involved in the manifestations of the disease. Today, there is a new, very successful, line of treatment of patellar tendinosis in the form of Doppler guided sclerosing injections. However, a few patients seem resistant to this therapy. Therefore, we have in this pilot study investigated biopsies from the patellar tendon of three such therapy-resistant patients, using immunohistochemistry. In situ hybridization was also applied. Comparisons were made with a material of specimens from both normal (n=16) and tendinosis (n=7) tendons, also previously examined. The study showed that there were extensive immunoreactions for choline acetyltransferase (ChAT) and vesicular acetylcholine transporter, as well as for the M(2) muscarinic acetylcholine receptor, in the overwhelming majority of the tenocytes. The immunoreactions were more pronounced than those generally obtained in the tendinosis tissue of the previously studied patients and clearly more pronounced than those of patellar tendon tissue of controls. Also, for the first time, we here present findings of mRNA for ChAT within tenocytes. In conclusion, it appears as if there is an excessive local acetylcholine (ACh) production and an occurrence of marked ACh effects in cases of severe tendinosis. An excessive production of local ACh might be related to pain sensation and the processes that occur in tendinosis development, such as cell proliferation. Thus, the results of this pilot study suggest that non-neuronal ACh is highly involved in the pathology of therapy-resistant patellar tendinosis. PMID- 17289084 TI - Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy. AB - Oxidative stress has been implicated in pathophysiology of diabetic neuropathy. All the pathways responsible for development of diabetic neuropathy are linked to oxidative stress in one way or the other. In the present study, we have targeted oxidative stress in diabetic neuropathy using resveratrol, a potent antioxidant. Eight weeks streptozotocin-diabetic rats developed neuropathy which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and increased thermal hyperalgesia. The 2-week treatment with resveratrol (10 and 20 mg/kg, i.p.) started 6 weeks after diabetes induction significantly ameliorated the alterations in MNCV, NBF, and hyperalgesia. Resveratrol also attenuated enhanced levels of malondialdehyde (MDA), peroxynitrite and produced increase in catalase levels in diabetic rats. There was marked reduction in DNA fragmentation observed after resveratrol treatment in diabetic rats as evident from decrease in Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) positive cells in sciatic nerve sections. Results of the present study suggest the potential of resveratrol in treatment of diabetic neuropathy and its protective effect may be mediated through reduction in oxidative stress and DNA fragmentation. PMID- 17289085 TI - Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. AB - In this study, we investigated the antidepressant-like effect of piperine in mice exposed to chronic mild stress (CMS) procedure. Repeated administration of piperine for 14 days at the doses of 2.5, 5 and 10 mg/kg reversed the CMS-induced changes in sucrose consumption, plasma corticosterone level and open field activity. Furthermore, the decreased proliferation of hippocampal progenitor cells was ameliorated and the level of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS stressed mice was up-regulated by piperine treatment in the same time course. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and lactic dehydrogenase (LDH) assays showed that piperine (6.25-25 microM) or fluoxetine (FLU, 1 microM) dose-dependently protected primary cultured hippocampal neurons from the lesion induced by 10 microM corticosterone (CORT). Reverse transcription-polymerase chain reaction (RT PCR) was used to detect the messenger ribonucleic acid (mRNA) level of BDNF in cultured neurons. Treatment with piperine (6.25-25 microM) for 72 h reversed the CORT-induced reduction of BDNF mRNA expression in cultured hippocampal neurons. In summary, up-regulation of the progenitor cell proliferation of hippocampus and cytoprotective activity might be mechanisms involved in the antidepressant-like effect of piperine, which may be closely related to the elevation of hippocampal BDNF level. PMID- 17289086 TI - Effect of long-term fluoxetine treatment on the human serotonin transporter in Caco-2 cells. AB - Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) broadly used in the treatment of human mood disorders and gastrointestinal diseases involving the serotoninergic system. The effectiveness of this therapy depends on repeated long term treatment. Most of the long-term studies in vivo of SSRI effects on serotoninergic activity have focused on their effects on autoreceptors or postsynaptic receptors. The chronic effect of SSRIs on the activity of the serotonin transporter (SERT) has been less studied and the results have been contradictory. The aim of this study was to determine the specific effect of long term fluoxetine treatment on human serotonin transporter (hSERT) in vitro, by using the human enterocyte-like cell line Caco-2. Results show that fluoxetine diminished the 5-HT uptake in a concentration-dependent way and that this effect was reversible. Fluoxetine affected mainly the hSERT transport rate by reducing the availability of the transporter in the membrane with no significant alteration of either the total hSERT protein content or the hSERT mRNA level. These results suggest that the effect of fluoxetine on the expression of hSERT is post-translational and has shown itself to be independent of PKC and PKA activity. This study may be useful to clarify the effect of the long-term fluoxetine therapy in both gastrointestinal and central nervous system disorders. PMID- 17289087 TI - Neuro-immune interactions via the cholinergic anti-inflammatory pathway. AB - The overproduction of TNF and other cytokines is associated with the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed "the cholinergic anti-inflammatory pathway" that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent excessive inflammation. Experimental evidence indicates that vagus nerve cholinergic anti-inflammatory signaling requires alpha7 nicotinic acetylcholine receptors expressed on non-neuronal cytokine-producing cells. Alpha7 nicotinic acetylcholine receptor agonists inhibit cytokine release and protect animals in a variety of experimental lethal inflammatory models. Knowledge related to the cholinergic anti-inflammatory pathway can be exploited in therapeutic approaches directed towards counteracting abnormal chronic and hyper-activated inflammatory responses. PMID- 17289088 TI - Roles played by lymphocyte function-associated antigen-1 in the regulation of lymphocytic cholinergic activity. AB - Lymphocytes possess the essential components of a cholinergic system, including acetylcholine (ACh); choline acetyltransferase (ChAT), its synthesizing enzyme; and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Stimulation of lymphocytes with phytohemagglutinin, which activates T cells via the T cell receptor/CD3 complex, enhances the synthesis and release of ACh and up-regulates expression of ChAT and M(5) mAChR mRNAs. In addition, activation of protein kinase C and increases in intracellular cAMP also enhance cholinergic activity in T cells, and lymphocyte function associated antigen-1 (LFA-1; CD11a/CD18) is an important mediator of leukocyte migration and T cell activation. Anti-CD11a monoclonal antibody (mAb) as well as antithymocyte globulin containing antibodies against CD2, CD7 and CD11a all increase ChAT activity, ACh synthesis and release, and expression of ChAT and M(5) mAChR mRNAs in T cells. The cholesterol-lowering drug simvastatin inhibits LFA-1 signaling by binding to an allosteric site on CD11a (LFA-1 alpha chain), which leads to immunomodulation. We found that simvastatin abolishes anti-CD11a mAb-induced increases in lymphocytic cholinergic activity in a manner independent of its cholesterol-lowering activity. Collectively then, these results indicate that LFA 1 contributes to the regulation of lymphocytic cholinergic activity via CD11a mediated pathways and suggest that simvastatin exerts its immunosuppressive effects in part via modification of lymphocytic cholinergic activity. PMID- 17289089 TI - Hepatic granulomas induced by Schistosoma mansoni in mice deficient for connexin 43 present lower cell proliferation and higher collagen content. AB - Granuloma formation involves a coordinated interaction between monocytes and macrophages, epithelioid cells, lymphocytes, eosinophils, neutrophils and fibroblasts. It has been established that extracellular communication via cytokines is important for the assembly of granulomas. However, the importance of gap junctions and intercellular communication to granuloma formation and development had never been assessed. Connexins are proteins that form gap junctions, and connexin 43 (Cx43) is present in macrophages, lymphoid cells, myelogenous cells, fibroblasts and others. We analyzed the effect of heterologous deletion of Gja1 (Cx43 gene) on the formation and development of hepatic granulomas induced by Schistosoma mansoni eggs. Heterozygous (Cx43(+/-)) and wild type (Cx43(+/+)) mice were infected subcutaneously with S. mansoni cercarie and evaluated after 6, 8 and 12 weeks. Granuloma cells express Cx43, as revealed by real-time PCR in isolated granulomas, and by immunohistochemistry. Cx43 expression was reduced in Cx43(+/-) mice, as expected. No differences in the average area of granulomas or number of cells per granuloma were observed between mice of different genotypes. However, granuloma cells from Cx43(+/-) mice displayed a reduced index of the proliferating cell nuclear antigen (PCNA) labeling at 8 and 12 weeks post-infection. Moreover, Cx43(+/-) granulomas unexpectedly presented a higher degree of fibrosis, quantified by morphometric analysis in Sirius Red-stained slides. Our results indicate that the deletion of one allele of the Cx43 gene, and possibly the reduced gap junction intercellular communication capacity (GJIC), may impair the interactions between granuloma cells, reducing their proliferation and increasing their collagen content, thereby modifying the characteristics of S. mansoni granuloma in mice. PMID- 17289090 TI - Particulate organic matter uptake rates of two benthic filter-feeders (Sabella spallanzanii and Branchiomma luctuosum) candidates for the clarification of aquaculture wastewaters. PMID- 17289091 TI - Ames test-negative carcinogen, ortho-phenyl phenol, binds tubulin and causes aneuploidy in budding yeast. AB - Ortho-phenyl phenol (OPP) is broad-spectrum of fungicides and antibacterial agents. OPP tested negative in an Ames system and positive with respect to the formation of tumors in the urinary bladder in rats when administered in diet, showing attributes of an Ames test-negative carcinogen. It has also been demonstrated that OPP does not bind or cleave DNA in vivo or in vitro, rather dose-dependent protein binding in OPP-treated rats was observed. OPP, however, generates chromosomal aberrations including aneuploidy. Thus, the steps by which Ames test-negative carcinogens exert their effects need to be elucidated. Here, we used an assay of loss of heterozygosity (LOH) in Saccharomyces cerevisiae to determine the biological effects of OPP and its hepatic metabolite phenyl hydroquinone (PHQ). LOH was found to be induced by OPP and PHQ because of a functional chromosome loss: aneuploidy. PHQ bound to and interfered with the depolymerization of tubulin in vitro and arrested the cell-cycle at M and G1. These results indicate that OPP and PHQ damaged tubulin to cause mis-segregation of chromosome by delaying cell-cycle progression through mitosis, and as a consequence caused aneuploidy. PMID- 17289092 TI - Barbiturate activation and modulation of GABA(A) receptors in neocortex. AB - We determined if anesthetic and anti-epileptic barbiturates inhibit neurons by different mechanisms. Current- and voltage-clamp recordings were made from somatosensory neurons of neocortex and some thalamocortical neurons in coronal brain slices of rats. We compared effects of pentobarbital, amobarbital, and phenobarbital on inhibitory postsynaptic currents (IPSCs) mediated by gamma aminobutyric acid (GABA), input conductance, and evoked action potential firing. In neocortex, pentobarbital (EC(50)=41 microM) and amobarbital (EC(50)=103 microM) increased the decay time constant of GABA(A)ergic IPSCs. At higher concentrations, pentobarbital and amobarbital shunted firing by increasing input conductance through agonism at GABA(A) receptors. At anti-epileptic concentrations, phenobarbital increased the IPSC decay time constant (EC(50)=144 microM), and shunted firing by agonism at GABA(A) receptors (EC(50)=133 microM). In thalamocortical neurons, similar concentrations of phenobarbital had negligible effects on GABA(A)ergic IPSCs, conductance, and firing. In contrast to their thalamic actions, barbiturates inhibit neocortical neurons mostly through GABA receptors. Neocortical enhancement of inhibition by pentobarbital and amobarbital, combined with actions on thalamocortical neurons, may contribute to redundant mechanisms of anesthesia. The ability of phenobarbital at anti epileptic concentrations to inhibit neocortical firing by direct activation and modulation of GABA(A) receptors relates to its specialized therapeutic effects. PMID- 17289094 TI - Oleanane-type triterpenes from the flowers, pith, leaves, and fruit of Tetrapanax papyriferus. AB - Four oleanane-type triterpenes, 3alpha,21beta,22alpha-trihydroxy-11,13(18) oleanadien-28-oic acid (1), 3-epi-papyriogenin C (2), 21-O-acetyl-21-hydroxy-3 oxo-11,13(18)-oleanadien-28-oic acid (3) and 3beta-hydroxy-21-oxo-11,13(18) oleanadien-28-oic acid methyl ester (4), together with four known triterpenes, were isolated from Tetrapanax papyriferus (Hook) K. Koch. Papyriogenin A (8) exhibited anti-HIV activity and low cytotoxicity in acutely infected H9 lymphocytes. Their structures were determined by analysis of spectroscopic data, including by 1D and 2D NMR. PMID- 17289093 TI - Hypothalamic and hindbrain NPY, AGRP and NE increase consummatory feeding responses. AB - Feeding behavior is comprised of both appetitive and consummatory responses to food. Appetitive responses include the motivated acquisition of food. Consummatory responses, including swallowing, are those that move the food from the mouth to the stomach. Intraoral delivery of liquid food bypasses the requirement for appetitive responses and has been used to examine consummatory responses directly in intact rats. In the present study, we administered neuropeptide Y (NPY), agouti-related protein (AGRP) and norepinephrine (NE), into the paraventricular nucleus of the hypothalamus (PVN) or into the fourth cerebral ventricle to examine their effects on the consummatory component of feeding behavior in the rat. To measure consummatory responses, milk (40% lactose free cow's milk diluted with water) was infused intraorally through a chronic cheek fistula (1 ml/min), using an alternating 5 min on -1 min off schedule, until rejection occurred. We found that both hypothalamic and fourth ventricle injections of NPY, AGRP and NE significantly increased consumption of the intraorally-delivered milk. Our results indicate that the circuitry for modulation of consummatory ingestive responses includes NE, NPY and AGRP receptors operating in both hypothalamic and hindbrain sites. PMID- 17289095 TI - Future public health delivery models for Native American tribes. AB - BACKGROUND: More and more Native American tribes are assuming control of their own public health care delivery systems by contracting the functions of the Indian Health Service (IHS) through the provisions of P.L. (public law) 93-638, the Indian Self-Determination and Education Assistance Act. In doing this, some Native American tribes are making decisions to create or plan their own departments of public health. In Arizona, the Gila River Indian Community has already established its own department of public health and the Navajo Nation is in the planning stages of establishing its own department of public health. METHODS AND RESULTS: This paper proposes three public health organizational delivery models to meet the public health needs of small, medium, and large Native American tribes. Information for these models was derived from interviews with officials associated with the Arizona Department of Health Services and leaders of Native American tribes. These models progress in size and complexity as we move from small to medium to large tribes. CONCLUSIONS: (a) service delivery should focus on both preventative and curative services; (b) services should be developed with input from the underserved population; (c) members of underserved populations should be trained to provide service to their communities; (d) one model of health service delivery will not be appropriate for all underserved populations; and (e) different models are required to respond to differing cultures, populations, and geographic locations. PMID- 17289096 TI - Accuracy of early fetal sex determination by ultrasonic assessment in goats. AB - The objective of this study was to determine the accuracy of early fetal sex determination by ultrasonic assessment of the relative location of the genital tubercle (GT) in goats at different stages of pregnancy as well as by the identification of fetal external genitalia. Pregnant animals were divided into three experimental groups (EI: n=21, EII: n=28, EIII: n=33). In EI, fetuses (n=27) were transrectally monitored daily from days 40 to 60 of pregnancy with a linear transducer (6.0 and 8.0MHz). In EII, fetuses (n=40) were examined once between days 45 and 70 of pregnancy by transrectal ultrasonography. In EIII fetuses (n=52) between days 100 and 120 of pregnancy, were submitted to a single transabdominal ultrasonography using a convex transducer (5.0 and 7.5MHz). Regardless of fetal sex diagnosis, 15/15 (EI), 13/16 (EII) and 9/14 (EIII) of single pregnancies and 10/12 (EI), 20/24 (EII) and 21/38 (EIII) of twin pregnancies were correctly identified. The accuracy of sex identification among EI (92.6%), EII (82.5%) and EIII (57.7%) was not statistically different (P>0.05). Identification of the GT in male fetuses was possible from day 45 onward. Changes in the GT position were not observed between days 53 and 60 of pregnancy. Accuracy of fetal sexing under field conditions is high in goats when ultrasound imaging is properly timed during pregnancy and when it is performed with proper equipment by experienced operators. PMID- 17289097 TI - [A text-book case of tropical facial elephantiasis]. AB - INTRODUCTION: Tropical facial elephantiasis is a nosological entity which can arise from various underlying causes: von Recklinghausen neurofibromatosis, lymphatic and cutaneodermal filarioses, deep mycosis. CASE REPORT: We report an exceptional case of tropical facial elephantiasis caused by onchocercosis and entomophtoromycosis (rhinophycomycosis). The patient's facial morphology was noted "hippopotamus-face" or "dog-face". DISCUSSION: Onchocercosis and entomophtoromycosis are two diseases known to cause facial elephantiasis. We have not however been able to find any case report in the literature of co-morbidity nor any information on factors predictive of concomitant occurrence. PMID- 17289098 TI - On the importance of dimensionality of space in models of space-mediated population persistence. AB - Spatially explicit models have become widely used in today's mathematical ecology to study persistence of populations. For the sake of simplicity, population dynamics is often analyzed with 1-D models. An important question is: how adequate is such 1-D simplification of 2-D (or 3-D) dynamics for predicting species persistence. Here we show that dimensionality of the environment can play a critical role in the persistence of predator-prey interactions. We consider 1-D and 2-D dynamics of a predator-prey model with the prey growth damped by the Allee effect. We show that adding a second space coordinate into the 1-D model results in a pronounced increase of size of the domain in the parametric space where predator-prey coexistence becomes possible. This result is due to the possibility of formation of a number of 2-D patterns, which is impossible in the 1-D model. The 1-D and the 2-D models exhibit different qualitative responses to variations of system parameters. We show that in ecosystems having a narrow width (e.g. mountain valleys, vegetation patterns along canals in dry areas, etc.), extinction of species is more probable compared to ecosystems having a pronounced second dimension. In particular, the width of a long narrow natural reserve should be large enough to guarantee nonextinction of species via interaction of 2 D population patches. PMID- 17289099 TI - The combination of donepezil and procyclidine protects against soman-induced seizures in rats. AB - Current treatment of nerve agent poisoning consists of prophylactic administration of pyridostigmine and therapy using atropine, an oxime and a benzodiazepine. Pyridostigmine does however not readily penetrate the blood-brain barrier giving ineffective protection of the brain against centrally mediated seizure activity. In this study, we have evaluated donepezil hydrochloride, a partial reversible inhibitor of acetylcholinesterase (AChE) clinically used for treating Alzheimer's disease, in combination with procyclidine, used in treatment of Parkinson's disease and schizophrenia, as prophylaxis against intoxication by the nerve agent soman. The results demonstrated significant protective efficacy of donepezil (2.5 mg/kg) combined with procyclidine (3 or 6 mg/kg) when given prophylactically against a lethal dose of soman (1.6 x LD(50)) in Wistar rats. No neuropathological changes were found in rats treated with this combination 48 h after soman intoxication. Six hours after soman exposure cerebral AChE activity and acetylcholine (ACh) concentration was 5% and 188% of control, respectively. The ACh concentration had returned to basal levels 24 h after soman intoxication, while AChE activity had recovered to 20% of control. Loss of functioning muscarinic ACh receptors (17%) but not nicotinic receptors was evident at this time point. The recovery in brain AChE activity seen in our study may be due to the reversible binding of donepezil to the enzyme. Donepezil is well tolerated in humans, and a combination of donepezil and procyclidine may prove useful as an alternative to the currently used prophylaxis against nerve agent intoxication. PMID- 17289100 TI - Biphasic effect of arsenite on cell proliferation and apoptosis is associated with the activation of JNK and ERK1/2 in human embryo lung fibroblast cells. AB - Biphasic dose-response relationship induced by environmental agents is often characterized with the effect of low-dose stimulation and high-dose inhibition. Some studies showed that arsenite may induce cell proliferation and apoptosis via biphasic dose-response relationship in human cells; however, mechanisms underlying this phenomenon are not well understood. In the present study, we aimed at investigating the relationship between biphasic effect of arsenite on cell proliferation and apoptosis and activation of JNK and ERK1/2 in human embryo lung fibroblast (HELF) cells. Our results demonstrated that cell proliferation may be stimulated at lower concentrations (0.1 and 0.5 microM) arsenite but inhibited at higher concentrations (5 and 10 microM). When cell apoptosis was used as the endpoint, the concentration-response curves were changed to U-shapes. During stimulation phospho-JNK levels were significantly increased at 3, 6, and 12 h after 0.1 or 0.5 microM arsenite exposure. Phospho-ERK1/2 levels were increased with different concentrations (0.1-10 microM) of arsenite at 6, 12, and 24 h. Blocking of JNK pathway with 20 microM SP600125 or ERK1/2 by 100 microM PD98059 significantly inhibited biphasic effect of arsenite in cells. Data in the present study suggest that activation of JNK and ERK1/2 may be involved in biphasic effect of arsenite when measuring cell proliferation and apoptosis in HELF cells. JNK activation seems to play a more critical role than ERK1/2 activation in the biphasic process. PMID- 17289101 TI - Modular architecture of the T4 phage superfamily: a conserved core genome and a plastic periphery. AB - Among the most numerous objects in the biosphere, phages show enormous diversity in morphology and genetic content. We have sequenced 7 T4-like phages and compared their genome architecture. All seven phages share a core genome with T4 that is interrupted by several hyperplastic regions (HPRs) where most of their divergence occurs. The core primarily includes homologues of essential T4 genes, such as the virion structure and DNA replication genes. In contrast, the HPRs contain mostly novel genes of unknown function and origin. A few of the HPR genes that can be assigned putative functions, such as a series of novel Internal Proteins, are implicated in phage adaptation to the host. Thus, the T4-like genome appears to be partitioned into discrete segments that fulfil different functions and behave differently in evolution. Such partitioning may be critical for these large and complex phages to maintain their flexibility, while simultaneously allowing them to conserve their highly successful virion design and mode of replication. PMID- 17289102 TI - Construction of an infectious cDNA clone for a Brazilian prototype strain of dengue virus type 1: characterization of a temperature-sensitive mutation in NS1. AB - To help understand the mechanism of pathogenesis of dengue virus (DV), we set out to create an infectious cDNA of the Brazilian prototype strain of DV serotype 1 (DV1-BR/90). PCR-amplified fragments of DV1-BR/90 cDNA were readily assembled into a subgenomic cDNA that could be used to produce replicating RNAs (replicons), lacking the structural protein-encoding regions of the genome. However, assembly of a cDNA capable of producing infectious virus was only possible using a bacterial artificial chromosome plasmid, indicating that DV1 sequences were especially difficult to propagate in E. coli. While characterizing our cDNA we discovered a fortuitous temperature-sensitive mutation in the NS1 encoding region. Using our infectious cDNA and a renilla luciferase-expressing replicon we were able to demonstrate that this mutation produced a defect in RNA replication at 37 degrees C, demonstrating that the DV1 NS1 protein plays an essential role in RNA replication. PMID- 17289103 TI - Infection of cells by Sindbis virus at low temperature. AB - Sindbis virus, which belongs to the family Togaviridae genus Alphavirus infects a variety of vertebrate and invertebrate cells. The initial steps of Sindbis virus infection involve attachment, penetration and uncoating. Two different pathways of infection have been proposed for Alphaviruses. One proposed mechanism involves receptor mediated virion endocytosis followed by membrane fusion triggered by endosome acidification. This virus-host membrane fusion model, well established by influenza virus, has been applied to other unrelated membrane-containing viruses including Alphaviruses. The other mechanism proposes direct penetration of the cell plasma membrane by the virus glycoproteins in the absence of membrane fusion. This alternate model is supported by both ultrastructural [Paredes, A.M., Ferreira, D., Horton, M., Saad, A., Tsuruta, H., Johnston, R., Klimstra, W., Ryman, K., Hernandez, R., Chiu, W., Brown, D.T., 2004. Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324(2), 373-386] and biochemical [Koschinski, A., Wengler, G., Wengler, G., and Repp, H., 2005. Rare earth ions block the ion pores generated by the class II fusion proteins of alphaviruses and allow analysis of the biological functions of these pores. J. Gen. Virol. 86(Pt. 12), 3311-3320] studies. We have examined the ability of Sindbis virus to infect Baby Hamster Kidney (BHK) cells at temperatures which block endocytosis. We have found that under these conditions Sindbis virus infects cells in a temperature- and time dependent fashion. PMID- 17289104 TI - Early cytokine mRNA expression profiles predict Morbillivirus disease outcome in ferrets. AB - Severe immunosuppression is a hallmark of Morbillivirus infections. To study the underlying mechanisms, we have developed a ferret model of canine distemper virus infection. The model reproduces all clinical signs of measles, but the lack of ferret-specific reagents has limited the characterization of the cellular immune response. Towards this, we cloned ferret cytokines and established semi quantitative real-time PCR assays. To demonstrate the utility of these assays we compared the cytokine profiles elicited by lethal and non-lethal strains during the prodromal phase. We observed a general lack of cytokine induction in animals that later succumbed to the disease, whereas survivors mounted a robust and sustained response. The newly developed cytokine assays strengthen and expand the ferret model not only for Morbillivirus pathogenesis studies but also for several other human respiratory viruses including influenza and SARS. PMID- 17289105 TI - A psychophysical investigation into the preview benefit in visual search. AB - In preview search, half of the distracters are presented ahead of the remaining distracters and the target. Search under these conditions is more efficient than when all the items appear together (Watson & Humphreys, 1997). We investigated the mechanisms contributing to this preview benefit using an orientation discrimination task. In a display of vertical Gabors (all equidistant from fixation) one Gabor (chosen at random) was tilted (left or right). When half the non-tilted Gabors were previewed, thresholds increased less with the number of Gabors, relative to when all the Gabors appeared together (a preview benefit). In a further experiment, orientation noise was added to some of the Gabors. When all Gabors were presented simultaneously, orientation thresholds for the target increased. The effects of noise on thresholds was reduced, however, when the noisy Gabors were presented as a preview. Furthermore, there was less effect of noise in the preview condition than when observers were cued to a subset of Gabors (with a cue presented prior to the Gabors, adjacent to their positions). Visual information can be effectively excluded from the previewed locations to a greater degree than when attention is directed to a subset of display items. The implications for understanding the mechanisms involved in preview search are discussed. PMID- 17289106 TI - The effects of aging on motion detection and direction identification. AB - Random dot cinematograms were used to probe motion perception in human observers ranging from 23 to 81 years of age. Stimuli were either broadband directional Noise, which produces no experience of global motion flow, or a narrower band directional Signal, which tended to produce experiences of coherent, global direction flow. On each trial, subjects rated their certainty that a Signal had been presented, and used a computer mouse to indicate the direction of perceived global flow. At all ages, sensitivity to motion and accuracy of perceived direction improved significantly as stimulus duration increased from 75 to 470 ms. However, older subjects (>70 years of age) were significantly less sensitive to motion, and were significantly less accurate at identifying the direction of movement. A control experiment, which found that older subjects accurately perceived and remembered the orientation of a line, ruled out the possibility that the observed deficits in motion perception were due to an inability on the part of older subjects to manipulate the computer mouse. Those control results also showed that both younger and older observers maintained robust visual representations over durations ranging from .24 to 6.0s. The motion detection and identification results obtained from subjects less than 70 years of age were well fit by a simple multichannel model of motion, although different levels of additive internal noise were needed to fit detection data and direction identification data, suggesting that motion direction and identification are constrained by different mechanisms. To fit the data from the oldest subjects, however, the values of model parameters had to be significantly altered, either by increasing the level of additive internal noise substantially, or by a smaller increase in noise coupled with an increase in the bandwidth of the model's directionally selective channels. These results are qualitatively consistent with recent neurophysiological studies showing weaker directional selectivity and higher spontaneous noise in visual neurons of senescent monkeys and cats. PMID- 17289107 TI - Detection of virulence genes in Escherichia coli of an existing metabolic fingerprint database to predict the sources of pathogenic E. coli in surface waters. AB - A collection of 366 Escherichia coli strains from 10 host groups and surface waters were tested for the presence of 15 virulence genes associated with strains causing intestinal and extra-intestinal infections. The virulence genes included eaeA, VT1, 2 and 2e, LT1, ST1 and 2, Einv gene, EAgg gene, CNF1 and 2, papC, O111 and O157 side chain LPS. Of the 262 strains obtained from nine different hosts, 39 (15%) carried one or more of these virulence genes. These included six strains from humans, two from horses, eight from dogs, two from ducks, five from cattle, seven from chickens, four from pigs, two from sheep and three from deer. Of the remaining 104 strains obtained from water samples, 10 (10%) also carried one or more of the tested virulence genes. Of these, six had identical biochemical phenotypes (BPTs) to strains isolated from humans (two strains), dogs (two strains), chickens (one strain) and sheep (one strain) with 4 BPTs also carrying same virulence genes. Our results indicate that the sources of clinically important E. coli strains found in surface waters due to faecal contamination can be predicted by using a combination of biochemical fingerprinting method and the detection of virulence genes. From the public health point of view this information will be of great importance for evaluating the risk associated with public use of the catchment. PMID- 17289108 TI - Thermochemical decomposition of sewage sludge in CO2 and N2 atmosphere. AB - In this study, the effect of CO(2) on the thermal conversion of sewage sludge was investigated by means of the thermogravimetric analysis and the batch-type thermal process. The results showed that the kinetics of sewage sludge during thermal treatment under both N(2) and CO(2) atmospheres are quite similar and can be described by a pseudo bi-component separated state model (PBSM). It was, however, noticed that under CO(2) atmosphere, the first reaction was significantly accelerated whereas the secondary reaction temperature was shifted to a lower temperature. The apparent activation energies for the first decomposition reaction under both N(2) and CO(2) atmosphere, corresponding to the main decomposition typically at 305 degrees C were similarly attained at ca. 72 kJ mol(-1), while that of the second decomposition reaction was found to decrease from 154 to 104 kJ mol(-1) under CO(2) atmosphere. The typical reaction order of the decomposition under both N(2) and CO(2) atmosphere was in the range of 1.0 1.5. The solid yield was slightly reduced while the gas and liquid yields were somewhat improved in the presence of CO(2). Furthermore, CO(2) was found to influence the liquid product by increasing the oxygenated compounds and lessening the aliphatic compounds through the insertion of CO(2) to the unsaturated compounds resulting in the carboxylics and the ketones formation. PMID- 17289109 TI - Emission, distribution and leaching of methyl isothiocyanate and chloropicrin under different surface containments. AB - The environmental fate of fumigants methyl isothiocyanate (MITC) and chloropicrin (CP) is of great concern for potential air and groundwater contamination while retaining sufficient concentrations for pest control efficacy. The emission, gas phase distribution, leaching, and persistence of MITC and CP were examined in repacked columns filled with sandy soils under three surface conditions: tarp without irrigation, tarp with limited irrigation, and 5-d irrigation without tarp cover. For MITC, cumulative emission constituted 62%, 36%, and 0.3% of the amount applied under tarp without irrigation, tarp with limited irrigation, and 5-d irrigation without tarp surface conditions, respectively. The corresponding cumulative emission losses were 45%, 30%, and 5.4% for CP. During the first 24h after injection, soil air concentrations of the two fumigants were much higher in the 15-25cm depth range than other depths in the soil profile. Small amounts of leaching occurred for both fumigants, indicating potential for groundwater contamination should heavy rain fall or irrigation occurs immediately after soil fumigation. Very small amounts of residual MITC and CP (<2%) were found in the soil 24 days after the experiment. The study clearly showed that atmospheric emission and degradation were the two primary pathways of MITC and CP dissipation during soil fumigation. Emission could be effectively reduced with 5-d irrigation if small leaching is acceptable or be prevented. PMID- 17289110 TI - Dissipation of sulfosulfuron in water - bioaccumulation of residues in fish - LC MS/MS-ESI identification and quantification of metabolites. AB - Dissipation study of sulfosulfuron in natural water and its bioaccumulation in fish was conducted at 25+/-2 degrees C and at two different concentration levels 1mgl(-1) and 2mgl(-1). The dissipation data in water showed the DT50 and DT90 values 67-76 and 222-253 days and followed first order kinetics. Bioaccumulation of sulfosulfuron in fish was conducted under static conditions exposing the fish at one-tenth of sub-lethal concentration 9mgl(-1) and at double the concentration 18mgl(-1), for a period of 56 days. On different occasions fish samples were collected and analyzed. A HPLC-RF method was used for the quantification of sulfosulfuron and aminopyrimidine with the limit of quantification 0.001microg ml(-1). Results showed the accumulation of residues of sulfosulfuron in fish over the concentration range 0.009-0.496microg g(-1). Both in water and fish samples, identified the presence of metabolites aminopyrimidine, desmethyl sulfosulfuron, guanidine, sulfonamide, ethyl sulfone and rearranged amine. The formations of these metabolites are confirmed by LC-MS/MS analysis. An LC-MS/MS electro spray ionization technique was used for this purpose. One of the metabolite Aminopyrimidine was identified at higher concentration levels (0.01-0.1microg ml( 1)) when compared with other metabolites. Subsequently dissipation of aminopyrimidine in water and its bioaccumulation was also studied at the concentration level 1mgl(-1) and 2mgl(-1). The calculated DT50 and DT90 values are 66-68 days and 218-226 days, respectively. This followed first order kinetics. Three hundred days after the exposure complete demineralization was observed. PMID- 17289111 TI - Effects of sewage sludge amendment on heavy metal accumulation and consequent responses of Beta vulgaris plants. AB - Use of sewage sludge, a biological residue produced from sewage treatment processes in agriculture is an alternative disposal technique of waste. To study the usefulness of sewage sludge amendment for palak (Beta vulgaris var. Allgreen H-1), a leafy vegetable and consequent heavy metal contamination, a pot experiment was conducted by mixing sewage sludge at 20% and 40% (w/w) amendment ratios to the agricultural soil. Soil pH decreased whereas electrical conductance, organic carbon, total N, available P and exchangeable Na, K and Ca increased in soil amended with sewage sludge in comparison to unamended soil. Sewage sludge amendment led to significant increase in Pb, Cr, Cd, Cu, Zn and Ni concentrations of soil. Cd concentration in soil was found above the Indian permissible limit in soil at both the amendment ratios. The increased concentration of heavy metals in soil due to sewage sludge amendment led to increases in heavy metal uptake and shoot and root concentrations of Ni, Cd, Cu, Cr, Pb and Zn in plants as compared to those grown on unamended soil. Accumulation was more in roots than shoots for most of the heavy metals. Concentrations of Cd, Ni and Zn were more than the permissible limits of Indian standard in the edible portion of palak grown on different sewage sludge amendments ratios. Sewage sludge amendment in soil decreased root length, leaf area and root biomass of palak at both the amendment ratios, whereas shoot biomass and yield decreased significantly at 40% sludge amendment. Rate of photosynthesis, stomatal conductance and chlorophyll content decreased whereas lipid peroxidation, peroxidase activity and protein and proline contents, increased in plants grown in sewage sludge-amended soil as compared to those grown in unamended soil. The study clearly shows that increase in heavy metal concentration in foliage of plants grown in sewage sludge-amended soil caused unfavorable changes in physiological and biochemical characteristics of plants leading to reductions in morphological characteristics, biomass accumulation and yield. The study concludes that sewage sludge amendment in soil for growing palak may not be a good option due to risk of contamination of Cd, Ni and Zn and also due to lowering of yield at higher mixing ratio. PMID- 17289112 TI - Enrichment and isolation of endosulfan degrading and detoxifying bacteria. AB - In the present study, degradation of endosulfan by a mixed culture isolated from a pesticide-contaminated soil was studied in batch experiments. After two weeks of incubation, the mixed culture was able to degrade 73% and 81% of alpha and beta endosulfan respectively. Endodiol was identified by GC/MS as degradation intermediate. The toxicity studies of endosulfan before and after degradation were carried out using micronucleus assay on human polymorphonuclear cells. The findings suggested that the metabolism of endosulfan isomers by the mixed culture was accompanied by significant reduction in the toxicity. Studies were also carried out to quantify the degradation potential of the individual species in the mixed bacterial culture. Two cultures identified by 16S rRNA as Stenotrophomonas maltophilia and Rhodococcus erythropolis were found to be responsible for majority of the degradation by the mixed culture. S. maltophilia showed better degradation efficiency compared to that by R. erythropolis. This is the first report of endosulfan degradation using the above-mentioned organisms. PMID- 17289113 TI - High adult mortality among Hiwi hunter-gatherers: implications for human evolution. AB - Extant apes experience early sexual maturity and short life spans relative to modern humans. Both of these traits and others are linked by life-history theory to mortality rates experienced at different ages by our hominin ancestors. However, currently there is a great deal of debate concerning hominin mortality profiles at different periods of evolutionary history. Observed rates and causes of mortality in modern hunter-gatherers may provide information about Upper Paleolithic mortality that can be compared to indirect evidence from the fossil record, yet little is published about causes and rates of mortality in foraging societies around the world. To our knowledge, interview-based life tables for recent hunter-gatherers are published for only four societies (Ache, Agta, Hadza, and Ju/'hoansi). Here, we present mortality data for a fifth group, the Hiwi hunter-gatherers of Venezuela. The results show comparatively high death rates among the Hiwi and highlight differences in mortality rates among hunter-gatherer societies. The high levels of conspecific violence and adult mortality in the Hiwi may better represent Paleolithic human demographics than do the lower, disease-based death rates reported in the most frequently cited forager studies. PMID- 17289114 TI - Fiber type distribution in the shoulder muscles of the tree shrew, the cotton-top tamarin, and the squirrel monkey related to shoulder movements and forelimb loading. AB - Muscle fiber type composition of intrinsic shoulder muscles was examined in tree shrews, cotton-top tamarins, and squirrel monkeys with respect to their shoulder kinematics and forelimb loading during locomotion. Enzyme- and immunohistochemical techniques were applied to differentiate muscle fiber types on serial cross-sections of the shoulder. In the majority of the shoulder muscles, the proportions of fatigue resistant slow-twitch fibers (SO) and fatigable fast-twitch fibers (FG) were inversely related to each other, whereas the percentage of intermediate FOG-fibers varied independently. A segregation of fatigue resistant SO-fibers into deep muscle regions is indicative of differential activation of histochemically distinct muscle regions in which deep regions stabilize the joint against gravitational loading. In all three species, this antigravity function was demonstrated for both the supraspinatus and the cranial subscapularis muscle, which prevent passive joint flexion during the support phase of the limb. The infraspinatus muscle showed a high content of SO fibers in the primate species but not in the tree shrew, which demonstrates the "new" role of the infraspinatus muscle in joint stabilization related to the higher degree of humeral protraction in primates. In the tree shrew and the cotton-top tamarin, a greater proportion of the body weight is carried on the forelimb, but the squirrel monkey exhibits a weight shift to the hind limbs. The lower amount of forelimb loading is reflected by an overall lower proportion of fatigue resistant muscle fibers in the shoulder muscles of the squirrel monkey. Several muscles such as the deltoid no longer function as joint stabilizers and allow the humerus to move beyond the scapular plane. These differences among species demonstrate the high plasticity of the internal muscle architecture and physiology which is suggested to be the underlying reason for different muscle activity patterns in homologous muscles. Implications for the evolution of new locomotor modes in primates are discussed. PMID- 17289115 TI - The role of free water surface constructed wetlands as polishing step in municipal wastewater reclamation and reuse. AB - In Europe, the last two decades witnessed growing water stress, both in terms of water scarcity and quality deterioration, which prompted many municipalities for a more efficient use of the water resources, including a more widespread acceptance of water reuse practices. Treatment technology encompasses a vast variety of options. Constructed wetlands are regarded as key elements in polishing conventionally treated wastewater for recreational and environmental applications. A survey was conducted to assess the performance of tertiary free water surface constructed wetlands in treating both key and emerging contaminant categories in the perspective of water reuse. A database was created with information concerning systems with emerging and free-floating macrophytes. The database includes results from both full- and pilot-scale systems, and considers a broad variety of operating conditions. This paper provides an overview of the treatment performances of the constructed wetlands in the database and discusses their significance in the optic of water reclamation and reuse practices. PMID- 17289116 TI - Effects of initial climatic conditions on growth and accumulation of fluoride and nitrogen in leaves of two tropical tree species exposed to industrial air pollution. AB - Saplings of Tibouchina pulchra and Psidium guajava, cultivated under standardized soil conditions, were placed in two sites at Cubatao (state of Sao Paulo, southeast Brazil) to study the effects of air pollution on growth, biomass allocation and foliar nitrogen and fluoride concentrations. Thirty-six potted plants were maintained over two periods of one year (Jul/00 to Jun/01; Dec/00 to Nov/01) at each of two experimental sites with distinct levels of air pollution: Piloes River Valley (PV) with vegetation virtually unaffected by air pollution; and Mogi River Valley (MV) severely affected by pollutants released mainly by chemical, fertilizer, iron and steel industries. For both species, saplings growing at MV showed alterations of growth and biomass allocation, as well as increased leaf concentrations of nitrogen and fluoride. Comparing both experimental periods, the one starting in winter (the driest season in Southeastern Brazil) seemed to affect the saplings more severely, the differences of the measured parameters between MV and PV being higher than in the second period. Multivariate analysis revealed two groups of data: one representing the MV and the other the PV saplings. For both species, saplings growing at MV showed differences in chemical composition, growth and biomass allocation, compared with the PV saplings. The results suggested that seasonal conditions of the first months of sapling exposure (summer or winter) modulate the intensity of responses to pollution stress. PMID- 17289117 TI - Arsenic fractionation in agricultural acid soils from NW Spain using a sequential extraction procedure. AB - Arsenic fractionation has been studied in nine vineyard soils from a wine producing area in Galicia (NW Spain) characterized by an unusually high As content. Total As concentrations are 7 to 10 times higher the maximum values allowed by the legislation, reaching maximum value of 200 mg kg(-1). The study of As fractionation revealed that those fractions showing strong correlations to crystalline Fe and Al hydrous oxides (r>0.69, p<0.01 and r>0.71, p<0.01 respectively) represented, on average, higher than the 80% of total As. The low levels of mobile and potentially toxic As fractions (<4% of total As) suggest that its toxicity is partially minimized in these soils, although the modifications induced by soil management could promote an increase of As availability. PMID- 17289118 TI - Estimation of soil water repellency of different particle size fractions in relation with carbon content by different methods. AB - The water repellency of soils with different texture under different types of plant cover was determined by applying the WDPT and MED methods to both whole samples and the following size fractions: 2-1, 1-0.5, 0.5-0.25, 0.25-0.05 and <0.05 mm. Based on the results, the soils under maize crop and grassland, which were mostly wettable in the whole samples, exhibited water repellency in the finest fraction (<0.05 mm) as a result of its higher organic carbon content. On the other hand, all fractions in the forest soils, which were extremely water repellent, contributed to the overall repellency; in any case, the MED test revealed that the finest fraction was strongly repellent in the forest soils as well. PMID- 17289119 TI - Seasonal changes in mRNA encoding for cell stress markers in the oyster Crassostrea gigas exposed to radioactive discharges in their natural environment. AB - The North Cotentin area (Normandy, France) hosts several nuclear facilities among which the AREVA reprocessing plant of La Hague is responsible for controlled discharges of liquid radioactive wastes into the marine environment. The resulting increase in radioactivity is very small compared to natural radioactivity. However, concerns about environment protection prompted the scientific community to focus on the effects of the chronic exposure to low concentrations of radionuclides in non-human biota. This study contributes to the evaluation of the possible impact of radioactive discharges on the oyster Crassostrea gigas in the field. Real-time polymerase chain reaction was used to quantify the expression levels of genes involved in cell stress in the oyster. They included members of the heat shock protein family (Hsp70, Hsc72, Hsp90), superoxide dismutase (SOD) and metallothionein (MT). Times series measurements were built from periodic samplings in the natural environment in order to characterize the natural variability as well as possible seasonal fluctuations. The genes studied exhibited a general seasonal expression pattern with a peak value in winter. The data inversely correlated with seawater temperature and the nature of the relationship between gene expression and temperature is discussed. In parallel, oysters were collected in four locations on the French shores, exposed or not to radioactive liquid wastes from the nuclear facilities hosted in the North Cotentin. The comparison of data obtained in the reference location on the Atlantic coast (not exposed) and data from oysters of the English Channel (exposed) gave no evidence for any statistical difference. However, because of the complexity of the natural environment, we cannot rule out the possibility that other parameters may have masked the impact of radioactive discharges. This dense set of data is a basis for the use of the expression levels of those genes as biomarkers to address the question of the possible effects of chronic exposure of the oyster to low concentrations of radionuclides in controlled laboratory experimental conditions. PMID- 17289120 TI - Assessment of olive cake as soil amendment for the controlled release of triazine herbicides. AB - Organic matter-rich agricultural by-products are being produced in huge quantities and can be applied to soil as a disposal strategy. The application of two different rates (2 and 8% w/w) of olive cake to a Mediterranean calcareous soil resulted in an increased sorption of four triazine herbicides, which was higher for the more hydrophobic compounds (terbuthylazine and prometryn) and lower for the more polar ones (simazine and cyanazine). However, when the sorption coefficients were normalised to the total soil organic carbon (K(oc)), the results did not significantly differ between simazine and cyanazine which is an indication that the olive cake did not exert different sorption capacity for both compounds. On the contrary, K(oc) values for terbuthylazine and prometryn increased in the amended soils. Our results from experiments using mixtures of several pesticides suggest that competition for sorption sites resulted in a decrease of herbicide sorption. Desorption was hysteretical both for the amended and unamended soils, but the addition of olive cake at the highest dose diminished desorption of most of the herbicides. In conclusion, the addition of olive cake behaves as a promising method for reducing the risk of groundwater pollution by pesticides. PMID- 17289121 TI - Changes in soil sealing in Guadalajara (Spain): cartography with LANDSAT images. AB - The great urban and industrial development of the towns surrounding Madrid has caused an irreversible and rapid soil loss. In this paper, soil sealed evolution in Guadalajara province during the past 15 years, mainly in the capital, industrial district and small municipalities near Madrid, has been studied. This province has experimented a sharp reduction of the most fertile soils, located on the Henares valley, due to the action of new models of local and regional development. The main goal of this paper is the mapping of the covered soils in a pilot area of Spain. Supervised classification of Landsat images from 1989 to 2002 has been carried out. Geo-referred image analysis allows us to detect precisely the amount of covered soils and where this phenomenon has taken place. PMID- 17289122 TI - Comparison of the structural stability of pasture and cultivated soils. AB - The structural properties of two neighbouring soils from the NW of Spain were evaluated in order to elucidate the effect of management on the soil structural quality and soil organic carbon turnover. The two soils were developed on granite under a warm and humid climate, but differed in land use (pasture and cultivation). The pasture soil had more favourable structural properties than the cultivated soil, showing lower bulk density, higher porosity and water retention. Also, the pasture soil showed a higher mean aggregate diameter and aggregate stability against mechanical agitation in water, as well as lower soil loss under simulated rainfall. This increased structural stability of the pasture soil could be attributed to its higher soil organic matter (SOM) content. The effect of soil use and aggregate size on SOM mineralization was also investigated. Laboratory incubation experiments were conducted with 1-5 mm aggregates and disaggregated <1 mm soil. More C-CO(2) was released by SOM mineralization in the pasture soil than in the cultivated soil, thus indicating a higher microbial activity in the pasture soil. The respiratory quotient (C-CO(2)/Corg) was also higher in the pasture soil, which means that SOM in this soil is more accessible to microbial decomposition. Nevertheless no significant differences were observed between organic C mineralization in the disaggregated <1 mm soil and the undisturbed 5-1 mm aggregates. The overall results demonstrate the need to maintain adequate levels of OM by adding organic amendments or adopting lower impact cultivation practices such as reduced tillage. PMID- 17289123 TI - Health benefit evaluation of the energy use scenarios in Beijing, China. AB - Air pollution is one of the important causal factors for excess cardiorespiratory deaths and diseases. However, little information is available on health gains from clean energy usage in developing countries. In this study the expected population exposed to air pollutants was estimated under the different energy use scenarios by the year 2010, 2020 and 2030, respectively, in the urban area of Beijing, China. The concentration-response functions between air pollutants and the health endpoints were established using meta-analysis and regression models. The decreased cardiorespiratory deaths and diseases of the exposed population were predicted as the health benefits from air pollution reduction. We used daily measurements of particulate matter less than 10 mum in aerodynamic diameter (PM(10)) and sulphate dioxide (SO(2)) as air pollution indicators. The percentage of population exposed to higher level of PM(10) will be decreased significantly under the clean energy use scenario than that under the Baseline Scenario (i.e., business-as-usual scenario). Compared with the Baseline Scenario there will be, by 2010, 2020, and 2030, respectively, a decrease of 29-152, 30-212 and 39-287 acute excess deaths; and 340-1811, 356-2529 and 462-3424 chronic excess deaths associated with the reduction of PM(10) level; also a decrease of 237-331, 285 371 and 400-554 short-term excess deaths associated with the decrease of SO(2) level. Meanwhile, the number of respiratory and cardiovascular hospital admissions, outpatient visits to internal and paediatrics departments, total emergency room visits and asthma attacks will be remarkably reduced with the reduction of air pollution. Energy structure improvement could reduce ambient air pollution and produce substantial health benefits to the population in Beijing. These findings may have significant implications for other metropolitan cities, particularly in developing countries. PMID- 17289124 TI - Phosphorus retention in a coastal salt marsh in SE Spain. AB - Total and inorganic soil P were extracted from a coastal salt marsh in SE Spain receiving eutrophicated water of urban and agricultural origin. The greatest P contents were obtained within the upper 10 cm of soil of those sectors of the salt marsh most affected by urban waste water effluents. Most of the P was extracted using HCl, indicating that it is mainly bonded to Ca compounds. Only in sites with low CaCO(3) content was the quantity of P associated with Fe and Al oxides and hydroxides (extracted with NaOH) noticeable. PMID- 17289125 TI - Effects of alimentary lipemia and inflammation on platelet CD40-ligand. AB - INTRODUCTION: In patients with chronic hypercholesterolemia, the CD40-CD40L dyad is upregulated, contributing to the initiation and progression of atherosclerosis. Our aim was to describe the role of postprandial lipemia and inflammatory stimulation on platelet and monocyte activation and CD40-ligand (CD40L) levels. METHODS AND RESULTS: Before and 2 h after consumption of a defined fatty meal, whole blood samples of 31 healthy subjects were incubated with endotoxin (LPS). CD40-ligand and CD62P expression on platelets, tissue factor expression on monocytes and platelet-monocyte aggregates were measured with flow cytometry. Soluble CD40-ligand plasma levels were measured with an ELISA. After the meal, serum triglyceride levels increased from 137.6+/-60.5 mg/dl to 201.5+/-75.0 mg/dl. Expression of CD40L and CD62P on platelets and plasma levels of soluble CD40L were significantly decreased. No significant changes after the meal were observed concerning tissue factor expression on monocytes and platelet-monocyte aggregates. Addition of LPS showed no significant effect concerning CD40L or CD62P expression on platelets, whereas the amount of platelet-monocyte aggregates significantly increased under LPS stimulation after the fatty meal. CONCLUSIONS: Acute alimenatry lipemia leads to a decreased expression of CD40L on platelets and a reduced plasma level of sCD40L, suggesting an increased turnover in the CD40L system. CONDENSED ABSTRACT: Before and after a fatty meal, blood samples of 31 healthy subjects were incubated with LPS. After the meal, expression of CD40L and CD62P on platelets and plasma levels of soluble CD40L were significantly decreased. Addition of LPS showed no effect concerning CD40L or CD62P expression, whereas the amount of platelet-monocyte aggregates significantly increased under LPS stimulation after the fatty meal. PMID- 17289126 TI - Joint effects of eNOS gene T-786C and ADH2 Arg47His polymorphisms on the risk of premature coronary artery disease. AB - INTRODUCTION: Both T-786C mutation in endothelial nitric oxide synthase (eNOS) gene and alcohol dehydrogenase (ADH) gene polymorphism such as ADH3 gamma1/gamma2 have been reportedly associated with coronary artery disease (CAD). Since ADH2 Arg47His polymorphism is common in Asian population, the aim of this present study was to assess the interaction between eNOS gene T-786C and ADH2 Arg47His polymorphisms on premature CAD risk. MATERIALS AND METHODS: Hospital-based case control study was conducted with 167 premature CAD and 235 late-onset CAD patients. Polymerase chain reaction restriction fragment length polymorphism was used to detect the polymorphisms. Multivariate logistic regression model was performed to adjust the potential confounders and estimate odds ratios (ORs) with 95% confidence intervals (CIs). Synergy index (S) was the measure to assess the interaction as departure from additivity. RESULTS: After the adjustment for the potential confounders, and compared with the carriers of TT and Arg/Arg as the reference, the ORs with 95% CIs in parentheses of premature CAD were that 1.13 (0.19-6.59) for CT or CC and Arg/Arg carriers; 2.24 (0.77-6.49) for TT and Arg/His or His/His carriers; 4.18 (1.32-13.22) for CT or CC and Arg/His or His/His carriers, respectively. Based on those ORs, S was 2.32 (95% CI: 0.37 14.72). CONCLUSIONS: The mutant genotypes of eNOS gene T-786C mutation and the fast form of ADH2 Arg47His polymorphism had an additive interaction on the risk of premature CAD in Chinese population. Further investigations with big sample size are necessary for confirming this additive interaction. PMID- 17289127 TI - Long-term follow-up after neoadjuvant chemotherapy for high-risk cervical cancer during pregnancy. AB - BACKGROUND: We report on a patient with a high-risk cervical cancer during pregnancy treated with neoadjuvant chemotherapy (NACT) followed by radical surgery. CASE: A 38-year-old woman was diagnosed with FIGO stage IIA cervical cancer at 19 weeks' gestation. She received four cycles of cisplatin (50 mg/m2) and vincristine (1 mg/m2) at 3-week intervals starting at 23 weeks' gestation. A cesarean section with radical hysterectomy and pelvic lymphadenectomy was performed at 33 weeks, delivering a 1920 g male newborn. Histology showed a poorly differentiated squamous cell carcinoma with lymph vascular invasion and pelvic lymph node metastases. The patient received three further cycles of chemotherapy. Both mother and child are healthy at 80 months after the primary diagnosis. CONCLUSION: NACT followed by radical surgery may be effective in selected patients with invasive cervical cancer during pregnancy. PMID- 17289128 TI - Cancer free survival after CIN treatment: comparisons of treatment methods and histology. AB - OBJECTIVE: Cervical cancer is one of the most lethal cancers among women worldwide. Women are treated and followed-up in several different manners. Long term studies of cancer or death risks after different methods of treatment or after different initial histology are scarce. METHODS: A retrospective cohort study with 7466 women treated of CIN between 1974 and 2001 in Helsinki University Hospital followed-up until the end of 2003. The Cox model was used to determine differences in cancer free or overall survival between women treated of CIN with different methods or after different initial grade of CIN. RESULTS: Twenty-two cases of invasive cervical cancer (ICC) and 57 cases of CIN 3 after treatment of CIN were observed. There were no statistically significant differences in ICC free survival between different treatment methods or initial grade of CIN. In CIN 3 free survival, the hazard ratios for the 57 cases of CIN 3, when cold knife coagulation (CKC) was set as the reference, were 0.22 for laser, 0.55 for cryotherapy and 0.31 for LEEP. In CIN 3+ (CIN 3 or ICC) free survival, the hazard ratios of 79 CIN 3+ cases (CKC reference) were 0.25 for laser, 0.50 for cryotherapy and 0.27 for LEEP. There were no differences in overall survival between different grades of initial CIN. CONCLUSIONS: The CKC seems to be the least favorable in terms of both further cancer and CIN 3 risk. The follow-up has to be well organized because the post-treatment cancer risk is independent of the initial grade of CIN. PMID- 17289129 TI - Vascular endothelial growth factor gene polymorphisms in ovarian cancer. AB - BACKGROUND: Polymorphisms within the vascular endothelial growth factor (VEGF) gene, the most important regulator of angiogenesis and vascular permeability, were shown to be independently associated with an impaired prognosis in various malignancies. No data have been reported in ovarian cancer. METHODS: In the present multi-center study, we examined three common polymorphisms within the VEGF gene (VEGF +405G/C, VEGF -460C/T, and VEGF +936C/T) in 553 Caucasian patients with ovarian cancer using pyrosequencing. RESULTS: The three investigated polymorphisms did not correlate with any of the investigated clinico pathological parameters. In univariate and multivariate models, only FIGO stage and patient's age at diagnosis, but not any polymorphism or any haplotype were correlated with patients' overall survival. CONCLUSIONS: In our large multi center study, the investigated VEGF gene polymorphisms were not associated with prognosis in patients with ovarian cancer. PMID- 17289130 TI - Behavioral sensitization produced by a single administration of apomorphine: implications for the role of Pavlovian conditioning in the mediation of context specific sensitization. AB - The present study examined the minimal number of exposures to the D1/D2 agonist apomorphine capable of producing behavioral sensitization. Rats received one (experiment 1) or two administrations on two successive days (experiment 2) of apomorphine (0.5 and 2.0 mg/kg) paired or unpaired to an open-field environment. After 2 days of drug withdrawal, the rats received a challenge injection with the same dose of apomorphine (sensitization test) and locomotion, rearing and sniffing were measured. The results of the first experiment showed that locomotor sensitization occurred after a single acute exposure to apomorphine and that 0.5 and 2.0 mg/kg treatments were equally effective. This sensitization effect was context-specific and was limited to locomotion. The second experiment revealed a differential dose effect on the sensitization test. Two treatments with 2.0 mg/kg potentiated locomotor sensitization as compared with a single treatment but two treatments with 0.5 mg/kg did not increase the sensitization effect more than the single 0.5 mg/kg treatment. This result indicates an interaction between drug dose and frequency of drug treatment for the induction of apomorphine locomotor sensitization. In that the sensitization effects are considered to be a core contributor to psychostimulant addiction, the present findings are of importance to understanding addiction because they indicate that sensitization processes can be initiated with a single drug experience and amplified with exposure to higher drug dosage levels. PMID- 17289131 TI - Baicalein improves cognitive deficits induced by chronic cerebral hypoperfusion in rats. AB - The aim of this study is to investigate the effects of baicalein on cognitive impairment and neuronal degeneration in a rat model of chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (2VO). It was found that baicalein (2 or 4 mg/kg/day, i.p.) significantly improved 2VO-induced cognitive deficits and neuropathological changes. Biochemical and histological examinations revealed that baicalein reduced the increased activities of superoxide dismutase (SOD) and malondialdehyde (MDA), and attenuated the decreased activities of glutathione peroxidase (GPx) and catalase in 2VO rats. The results of the present observation suggest that baicalein has therapeutic potential for the treatment of vascular dementia, which is most likely related, at least in part, to its antioxidant action. PMID- 17289132 TI - The correct methacholine challenge delivery method? PMID- 17289133 TI - Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge. AB - BACKGROUND: IL-13 is believed to be a central mediator of asthma, and TGF-beta1 is a key downstream mediator in the development of IL-13-mediated asthma phenotypes. OBJECTIVE: To evaluate the biological roles of basic fibroblast growth factor (FGF2) in phenotype expression in transgenic (TG) mice overexpressing lung-specific TGF-beta1, and the therapeutic effects of recombinant FGF2 in the development of asthma phenotypes. METHODS: To evaluate the roles of FGF2 in airway hyperresponsiveness (AHR) expression induced by high levels of TGF-beta1, TGF-beta1 TG (+) mice were bred with FGF2-deficient mice. To evaluate the therapeutic effects of recombinant FGF2 (rFGF2) in the development of asthma, mice were given 10 mug of rFGF2 subcutaneously once a day, 1 hour before the allergen challenge in an asthma mouse model. AHR was evaluated using noninvasive whole-body plethysmography, mucus production by diastase-resistant periodic acid Schiff (DPAS) staining, and lung inflammation using bronchoalveolar lavage (BAL) cellularity and lung histology. RESULTS: AHR decreased in TGF-beta1 TG (+) mice and was accompanied by the upregulation of FGF2 mRNA expression in lung tissues, when compared with littermate wild-type control mice. Interestingly, AHR was enhanced markedly in TGF-beta1 (+) mice with homozygous FGF2 gene disruption. In an asthma mouse model, AHR, mucus production, and lung inflammation were inhibited markedly by rFGF2 treatment. This inhibition was accompanied by downregulation of the allergen-induced proliferation of T cells from regional lymph nodes. CONCLUSION: FGF2 seems to be a key inhibitor in the development of AHR, and rFGF2 treatment constrains the development of asthma phenotypes. PMID- 17289134 TI - The use of imaging techniques for assessing severe childhood asthma. AB - Computed tomography (CT) scans are usually performed in children with asthma to exclude alternative diagnoses. Technical improvements of high-resolution CT (HRCT) scans have increased the spatial resolution sufficiently for the theoretical quantification of bronchial wall thickening of the proximal airways and the assessment of small airway disease by the extent and degree of low attenuation areas, which are believed to represent air trapping. In contrast with adults, very few studies have been performed in children. The results suggest that the HRCT scan might be useful as a noninvasive technique for airway inflammation and airway remodeling. In the future, the potential use of HRCT scans for determining optimal treatment should be evaluated. However, several issues remain to be resolved, including the validity of algorithm reconstruction, the imaging parameters to be used, and the application of this technique to young children. Furthermore, because of its cost and the irradiation involved, this examination is highly unlikely to be used routinely for the management and follow up of all children with asthma but will likely be restricted to patients with severe asthma. PMID- 17289135 TI - Probiotics during the first 7 years of life: a cumulative risk reduction of eczema in a randomized, placebo-controlled trial. PMID- 17289136 TI - The joint impact of cardiovascular risk factors upon medical costs. AB - OBJECTIVE: The joint impact of obesity, hypertension, and hyperglycemia upon medical costs is not well known. Our objective was to evaluate the joint impact of these cardiovascular risk factors upon medical costs in the rural Japanese population. METHODS: The data were derived from a 6-year prospective observation of National Health Insurance beneficiaries in rural Japan. Data on blood chemistry tests, blood pressure, weight, and height were obtained from an annual health check-up provided by the local municipalities in 1995. We prospectively collected data on medical costs over a 6-year period for 12,340 subjects (5306 men and 7034 women) without prior histories of cardiovascular disease or cancer. RESULTS: Mean medical costs for individuals being overweight/obese, hypertensive, and hyperglycemic were 91.0% higher than those for individuals without any of these three cardiovascular risk factors. In this cohort, 17.2% of total medical costs were attributable to these three risk factors. CONCLUSION: Overweight/obesity, hypertension, and hyperglycemia could have a large impact on health care resources in rural Japan. PMID- 17289137 TI - Materialist and post-materialist values and cannabis smoking among young adults: a population-based study in southern Sweden. AB - OBJECTIVES: The association between materialist, mixed and post-materialist values, and the experience of cannabis smoking among young adults was investigated. METHODS: The 2004 public health survey in Skane, southern Sweden, is a cross-sectional study with a 59% response rate. The 6787 persons aged 18-34 years included in this study answered a postal questionnaire. A logistic regression model was used to investigate the association between materialist, mixed and post-materialist values and ever having experienced cannabis smoking. The multivariate analysis was performed to investigate the importance of possible confounders (age and education) on the differences in ever having experienced cannabis smoking according to materialist, mixed and post-materialist values. RESULTS: 28% of the men and 17% of the women had ever experienced cannabis smoking. The experience of cannabis smoking was significantly and positively associated with post-materialist values among both men and women. The odds ratios were 2.4 (1.8-3.1) for men with post-materialist values compared to men with materialist values, and 3.1 (2.4-4.0) for women with post-materialist values compared to women with materialist values. CONCLUSIONS: This study suggests that post-materialist values are positively associated with the risk of ever smoking cannabis. Because this is a cross-sectional study, the direction of causality remains to be investigated. PMID- 17289138 TI - Quantification of DNA binding, uptake, transmission and expression in bovine sperm mediated gene transfer by RT-PCR: effect of transfection reagent and DNA architecture. AB - In this study, we compared the transfection effectiveness of liposomes with the new transfection reagent FuGene 6 in bovine sperm mediated gene transfer (SMGT). Furthermore, we examined whether plasmid architecture affects overall efficiency by comparing two plasmids, one of them bearing an additional murine nontranscribed spacer (nts) insert (CMV-INF-tau-IRES-EGFP versus CMV-INF-tau-IRES EGFP-nts). To accomplish that, we quantified plasmid binding and uptake to spermatozoon and transfer and expression of foreign DNA into embryos by real time PCR. More plasmids bound to spermatozoa when treated with FuGene 6 than with liposome treatment (p<0.05) reaching highest counts in plasmids bearing the nts sequence (p<0.05). Mean number of plasmids taken up was significantly (p<0.05) affected by transfection strategy (1-3 versus 15-81 versus 120-162) with plasmids bearing the nts sequence being 2-8 fold more effective (p<0.05). Culture of SMGT derived embryos up to day 9 did not result in any difference in terms of cleavage rate (64.2-84.2%) and development to blastocyst stage (18.8-26.3%) between different groups. Insert of the nts fragment significantly (p<0.05) affected mean number of transmitted plasmids to 4-cell stage embryos (44 versus 7) and relative INF-tau mRNA expression level in day 9 blastocysts (7-8 fold). However, only six blastocysts (3.6%) exhibited green fluorescence indicating low EGFP protein production. In conclusion, we were able to show effectiveness of sperm mediated gene transfer is significantly affected by choice of transfection reagent and by plasmid architecture. PMID- 17289139 TI - Developmental stage of the oocyte during antral follicle growth and cumulus investment determines in vitro embryo development of sow oocytes. AB - The aim of the study was to determine the contribution of cumulus cells on the developmental competence of porcine oocytes during follicle growth. Oocytes from large (5-8mm) and small (2-3mm) follicles were cultured with or without follicle stimulating hormone (FSH), subsequently examined for nuclear stage and spindle morphology, or fertilized and cultured for embryo development, or analyzed for glutathione content. Additionally, the significance of cumulus investment, corona radiata cells, cumulus cell number and origin of cumulus cells for oocyte maturation were investigated. Small follicle oocytes cultured without FSH exhibited the highest incidence of spindle aberrations. Oocytes cultured without FSH exhibited reduced sperm penetration and blastocyst rates, and a higher proportion monospermic oocytes developed to the blastocyst stage when derived from large follicles. The glutathione content in oocytes increased during follicle growth and oocyte maturation, but no direct correlation between oocyte glutathione content and oocyte developmental capacity was observed. Oocytes with a bigger cumulus investment exhibited better embryo development. Oocytes with a single corona radiata cell layer (CROs) exhibited similar progression through meiosis to oocytes with more cumulus cell layers, but showed reduced embryo development. More blastocysts were observed when CROs were cultured with disconnected cumulus cells during IVM, but no blastocyst increase was observed when CROs were cocultured with a higher number of cumulus cells or with cumulus cells from large follicles. We conclude that increased developmental capacity of oocytes during follicle growth is intrinsic and whether cumulus cells originate from large or small follicles, their contribution to oocyte maturation remains unchanged. Further, cumulus investment can be used as a variable to predict oocyte developmental capacity. PMID- 17289140 TI - Action naming in anomic aphasic speakers: effects of instrumentality and name relation. AB - Many studies reveal effects of verb type on verb retrieval, mainly in agrammatic aphasic speakers. In the current study, two factors that might play a role in action naming in anomic aphasic speakers were considered: the conceptual factor instrumentality and the lexical factor name relation to a noun. Instrumental verbs were shown to be better preserved than non-instrumental verbs in a group of anomic aphasic speakers but not in a group of Broca's aphasic speakers. Name relation to a noun improved the performance of the anomic aphasic speakers as well. Again, no effect was found in the group of Broca's aphasic speakers. Verbs with a name relation to a noun were better retrieved in action naming than verbs without a name relation. These findings are discussed in terms of the spreading activation theory of Dell. (Dell, G. S. (1986). A spreading activation theory of retrieval in sentence production. Psychological Review 93, 283-321.). PMID- 17289141 TI - The effect of genetically engineered spider silk-dentin matrix protein 1 chimeric protein on hydroxyapatite nucleation. AB - Spider silks exhibit remarkable mechanical properties while dentin matrix protein 1 provides controlled nucleation and hydroxyapatite growth. In the present work, these two attributes were combined via genetic engineering to form a chimera, a clone encoding consensus repeats from the major protein in the spider dragline silk of Nephila clavipes fused to the carboxyl terminal domain of dentin matrix protein 1 (CDMP1). The objective was to exploit the self-assembly and material properties of silk proteins with controlled hydroxyapatite (HA) formation from CDMP1, for novel biomaterial composites. The purified recombinant protein retained native-silk like self-assembly properties and beta-sheet structure when formed into films and treated with methanol. When the chimeric protein in solution was incubated with CaCl(2,) the secondary structure shifted from random coil to alpha-helix and beta-sheet, due to the interactions between the CDMP1 domain and Ca(2+). The control protein without the CDMP1 domain did not undergo a similar transition. Films formed from the recombinant protein were mineralized using simulated body fluids and induced the formation of calcium-deficient carbonated HA, Ca(10)(PO(4))(6)(OH)(2) based on SEM, EDS, FTIR and TEM analysis. This mineral phase was not formed on the films formed from the control spider silk protein without the CDMP1 domain. Considering the osteoconductivity of HA and the novel material features of spider silks, these new hybrid systems offer potential as biomaterials for a number of potential applications. PMID- 17289143 TI - Cytotoxicity of alkylphenols and alkylated non-phenolics in a primary culture of rainbow trout (Onchorhynchus mykiss) hepatocytes. AB - Alkylphenols are common aquatic pollutants originating from industrial use of the compounds themselves or as biodegradation products of alkylphenol polyethoxylates. The cytotoxicity of a range of alkylphenols and alkylated non phenolics were assessed in a primary culture of rainbow trout (Onchorhynchus mykiss) hepatocytes to construct a structure-toxicity relationship for this group of ubiquitous aquatic pollutants. Metabolic inhibition and loss of membrane integrity were used as cytotoxic endpoints through use of the cellular markers Alamar blue and 5-carboxyfluorescein diacetate acetoxymethyl ester, respectively. The results show that cytotoxicity increased with the hydrophobicity of the alkylphenols for compounds with logK(OW)<4.9. Normal chained alkylphenols, branched alkylphenols and multi-substituted alkylphenols with logK(OW)4.9 deviated clearly from this relationship. The alkylphenols displayed greater cytotoxicity than alkylated non-phenolics and it is proposed that most alkylated non-phenolic caused non-polar narcosis (baseline toxicity) whereas the alkylphenols caused polar narcosis. Observations that metabolic inhibition occurred at lower concentrations than loss of membrane integrity for most chemicals indicated that interference with cellular metabolic functions was the main cause of cytotoxicity. Metabolic inhibition corresponded better than loss of membrane integrity to reported acute toxicity to fish, although the in vivo acute toxicity of hydrophobic compounds (logK(OW)>2-3) was clearly underestimated by both endpoints. PMID- 17289142 TI - Intra-VTA CART 55-102 reduces the locomotor effect of systemic cocaine in rats: an isobolographic analysis. AB - CART (cocaine- and amphetamine-regulated transcript) peptides appear to be mediators or modulators of psychostimulant drugs. An interesting result in the nucleus accumbens has been that injection of CART peptide has no effect by itself on locomotor activity, but it reduces the locomotor activity induced by cocaine or amphetamine. However, in the ventral tegmental area (VTA), injections of CART peptide have been shown to increase locomotor activity, although to a lesser degree [Kimmel, H.L., Gong, W., Vechia, S.D., Hunter, R.G., Kuhar, M.J., 2000. Intra-ventral tegmental area injection of rat cocaine and amphetamine-regulated transcript peptide 55-102 induces locomotor activity and promotes conditioned place preference. J. Pharmacol. Exp. Ther. 294, 784-792]. This study was carried out to clarify the interaction of intra-VTA CART 55-102 and systemic cocaine on locomotor activity. The CART-cocaine interaction has been examined using the rigorous isobolographic approach. This type of analysis permits an assessment of additivity, subadditivity, or synergism of two substances. By measuring locomotor activity and using a range of doses of CART peptide and cocaine, both alone and together, with different dosing strategies, clear evidence of subadditivity was found. CART reduced the locomotor activating effects of systemic cocaine, especially at higher doses of CART. These results imply that intra-VTA CART is not simply acting in the same manner as cocaine, and is likely to oppose the action of cocaine. This has implications for the physiological significance of CART-DA (dopamine) interactions and for medications development. PMID- 17289144 TI - Strain difference in sensitivity to 3,4-dichloroaniline and insect growth regulator, fenoxycarb, in Daphnia magna. AB - Acute and reproductive toxicity tests were conducted on seven strains of Daphnia magna from six laboratories in five countries. 3,4-Dichloroaniline (DCA) and fenoxycarb were used as test chemicals. Acute toxicity tests revealed that estimated EC(50) (50% effective concentration) values for DCA varied by a factor of 2.1 among strains (310-640 microg/L), whereas the EC(50) values for fenoxycarb varied by a factor of 4 (210-860 microg/L). EC(50) values for reproductive toxicity tests with DCA ranged from 5.9 to 38 microg/L among strains. Fenoxycarb exposure induced the production of male neonates in all the strains used in the present study. Estimated EC(50) values for the induction of male offspring were highly variable among strains: sensitivity to fenoxycarb differed by a factor of approximately 23 overall (0.45-10 microg/L). The present pre-validation tests suggest that induction of male sex in neonates by a juvenile hormone analog is universal among genetically different strains. Decreased total numbers of neonates at increased concentrations of fenoxycarb as well as other juvenoids may, however, obscure the incidence of male neonates production in the 21-day reproduction tests due to the low statistical power. PMID- 17289145 TI - Perfluorinated chemicals in blood of residents in Catalonia (Spain) in relation to age and gender: a pilot study. AB - Fluorinated organic compounds (FOCs) are a group of chemicals widely used as surfactants, lubricants, polymers, and fire-fighting foams. Recent studies have shown the ubiquitous distribution of FOCs in the environment, wildlife, and humans. We here report the results of a pilot study conducted to provide preliminary data on the levels of 13 FOCs in the blood of 48 residents in Catalonia, Spain, in relation to gender and age (25+/-5 and 55+/-5 years). The highest mean concentration was obtained for perfluorooctane sulfonate (PFOS, 7.64 ng/ml), followed by perfluorohexane sulfonate (PFHxS, 3.56 ng/ml) and perfluorooctanoic acid (PFOA, 1.80 ng/ml). Four other FOCs showed mean levels between 0.30 and 0.44 ng/ml, whereas those of the remaining 6 compounds were below the detection limit. Regarding gender, the blood levels of PFHxS and PFOA were significantly higher (p<0.05) in men than in women, while differences according to age were only noted for PFHxS (p<0.05) and perfluorooctane sulfonamide (PFOSA) (p<0.001), for which the levels were higher in the younger (25+/-5 years) group of subjects. A significant correlation between PFOS levels and those of the remaining detected FOCs (except PFDA) was found. In general terms, the current FOC concentrations were lower than those found in recent studies concerning levels of these chemicals in human blood and serum of subjects from different countries. PMID- 17289146 TI - B7-1 mediated costimulation regulates pancreatic autoimmunity. AB - Costimulation by B7-1 and B7-2 molecules results in divergent biological effects. This is particularly striking in the NOD mouse, since the lack of B7-2 leads to complete protection from diabetes whereas the B7-1 deficiency causes exacerbation of disease. We tested the hypothesis that B7-1 costimulation suppresses pancreatic autoimmunity. We describe that the lack of B7-1 not only causes aberrant thymocyte maturation but also significantly enhances expansion, survival, and effector function of islet specific T cells in periphery. We also observed a significant reduction in the proportion of T-regulatory (T-regs) cells. Immunophenotypic analysis of T and APCs revealed a significantly lower frequency of T cells expressing the negative costimulatory receptor PD-1 in B7 1KO mice whereas the proportion of B7-H1 positive APCs was found to be significantly higher. Blocking studies in B7-1KO mice suggest that B7-H1 provides negative signals for anti islet CD4 and CD8 T-cell expansion but is differentially required for their priming. Our data demonstrate that deficiency of B7-1 mediated costimulation causes multitude of immunological defects, which involve reduction in T-regs and a concomitant enhancement of expansion, survival and effector potential of auto reactive T cells. PMID- 17289148 TI - Modified Jones' lacrimal bypass surgery with an angled extended Jones' tube. AB - PURPOSE: To analyze the outcome of modified Jones' lacrimal bypass surgery with an angled extended tube. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Patients with epiphora due to severe canalicular obstruction or dysfunction. Seventy-one Caucasian patients (90 tubes), operated between 1995 and 2005, were followed over a mean period of 3.2 years, ranging from 2 months to 10.4 years after surgery. INTERVENTION: A modified Jones' tube, with a 130-degree angled middle and extended length, was inserted using a transcaruncular technique without a dacryocystorhinostomy. In 6 tubes, an additional external dacryocystorhinostomy was performed for reasons of concurrent dacryomucocele. MAIN OUTCOME MEASURES: Patency and anatomic position of the tube and subjective relief of epiphora. RESULTS: The tube complications included nasal displacement in 12% of the tubes, lateral displacement in 11%, and nonpatency in 4%. The conjunctival complications were conjunctival overgrowth and caruncular granuloma, observed in 6% of the tubes. In all but 4 eyes, complications occurred within 2.7 months after the first tube implantation. After secondary surgery for a complication, 40% of the eyes needed a third intervention or more. The patients reported a comfortable relief of epiphora in 89% of the well-positioned patent tubes. CONCLUSION: The modified Jones' tube offers a good long-term outcome, with a tube displacement rate of 23%, mainly occurring within the first 3 months after surgery. PMID- 17289147 TI - Retinal nerve fiber layer thickness and visual sensitivity using scanning laser polarimetry with variable and enhanced corneal compensation. AB - PURPOSE: To compare the strength of the structure-function association between scanning laser polarimetry-measured retinal nerve fiber layer (RNFL) thickness and visual sensitivity. Two methods of corneal compensation were evaluated, variable corneal compensation (VCC) and enhanced corneal compensation (ECC). DESIGN: Observational case series. PARTICIPANTS: One hundred twenty-seven glaucoma (repeatable abnormal visual fields [VF] by pattern standard deviation and/or glaucoma hemifield test) or glaucoma suspect (glaucomatous-appearing discs by photograph assessment without field defects) participants in the University of California, San Diego Diagnostic Innovations in Glaucoma Study. METHODS: One eye of each participant was imaged using GDx VCC and GDx ECC on the same day. Visual fields tested using the Humphrey Field Analyzer (with Swedish interactive threshold algorithm) were obtained within 6 months of imaging. MAIN OUTCOME MEASURE: The associations (R2) using linear and logarithmic regression between RNFL thicknesses measured in 6 sectors (inferior, inferotemporal, temporal, superotemporal, superior, nasal) with VCC and ECC and VF sensitivities (decibel threshold measurements) measured in 6 corresponding sectors were compared. Comparisons were made using paired t tests on the log-transformed absolute values of regression residuals. RESULTS: Using GDx VCC, 32 scans had a typical scan score (TSS) < or = 78 (lowest quartile) and no ECC scans had TSS<86. Most RNFL thickness measurements obtained using GDx VCC were significantly greater than those measured using GDx ECC. Regional structure-function associations (R2) ranged from 0.03 (temporal RNFL) to 0.22 (superotemporal RNFL) for VCC and from 0.01 (temporal RNFL) to 0.26 (superotemporal RNFL) for ECC. Associations generally were slightly stronger for ECC than for VCC, although these differences were only significant for inferotemporal RNFL (R2 = 0.19 and 0.11, for ECC and VCC, respectively). CONCLUSION: The RNFL thickness associations with VF sensitivity are stronger using ECC compared with VCC, suggesting that ECC provides a better cross-sectional representation of visual function than VCC. PMID- 17289149 TI - Luminescence study of G-quadruplex formation in the presence of Tb3+ ion. AB - The interactions of Tb3+ with the quadruplex-forming oligonucleotide bearing human telomeric repeat sequence d(G(3)T(2)AG(3)T(2)AG(3)T(2)AG(3)), (htel21), have been studied using luminescence spectroscopy and circular dichroism (CD). Enhanced luminescence of Tb3+, resulting from energy transfer from guanines, indicated encapsulation of Tb3+ ion in the central cavity of quadruplex core. The ability of lanthanide ions (Eu3+ and Tb3+) to mediate formation of quadruplex structure has been further evidenced by the fluorescence energy transfer measurements with the use of oligonucleotide probe labeled with fluorescein and rhodamine FRET partners, FAM-htel21-TAMRA. The CD spectra revealed that Tb3+/htel21 quadruplex possesses antiparallel strand orientation, similarly as sodium quadruplex. Tb3+ binding equilibria have been investigated in the absence and the presence of competing metal cations. At low Tb3+ concentration (8 microM) Tb3+/htel21 quadruplex stability is very high (5 x 10(6) M(-1)) and stoichiometry of 5-7 Tb3+ ions per one quadruplex molecule is observed. Luminescence and CD titration experiments suggested that the cavity of quadruplex accommodates two Tb3+ ions and the remaining Tb3+ ions bind probably to TTA loops of quadruplex. Higher concentration of Tb3+ (above 10 microM) results in the excessive binding of Tb3+ ions that finally destabilizes quadruplex, which undergoes transformation into differently organized assemblies. Such assemblies (probably possessing multiple positive charge) exhibit kinetic stability, which is manifested by a very slow kinetics of displacement of Tb3+ ion by competing cations (Li+, Na+, K+). PMID- 17289150 TI - Conditional gene targeting in the mouse nervous system: Insights into brain function and diseases. AB - Conditional gene knockout represents an extremely powerful approach to study the function of single genes in the nervous system. The Cre-LoxP system is the most advanced technology for spatial and temporal control of genetic inactivation, and there is rapid progress using this methodology in neuroscience research. In this approach, mice with LoxP sites flanking the gene of interest (floxed mice) are bred with transgenic mice expressing Cre recombinase under the control of a selected promoter (Cre mice). This promoter is critical in that it determines the time and site of Cre expression. Cre enzyme, in turn, recombines the floxed gene and produces gene knockout. Here we review Cre mouse lines that have been developed to target either the entire brain, selected brain areas, or specific neuronal populations. We then summarize phenotypic consequences of conditional gene targeting in the brain for more than 40 genes, as reported to date. For many broadly expressed genes, brain-restricted knockout has overcome lethality of conventional knockout (KO) and has highlighted a specific role of the encoded protein in some aspect of brain function. In the case of neural genes, data from null mutants in specific brain sites or neurons has refined our understanding of the role of individual molecules that regulate complex behaviors or synaptic plasticity within neural circuits. Among the many developing functional genomic approaches, conditional gene targeting in the mouse has become an excellent tool to elucidate the function of the approximately 5000 known or unknown genes that operate in the nervous system. PMID- 17289151 TI - Behavioral evaluation of visual function of rats using a visual discrimination apparatus. AB - A visual discrimination apparatus was developed to evaluate the visual sensitivity of normal pigmented rats (n=13) and S334ter-line-3 retinal degenerate (RD) rats (n=15). The apparatus is a modified Y maze consisting of two chambers leading to the rats' home cage. Rats were trained to find a one-way exit door leading into their home cage, based on distinguishing between two different visual alternatives (either a dark background or black and white stripes at varying luminance levels) which were randomly displayed on the back of each chamber. Within 2 weeks of training, all rats were able to distinguish between these two visual patterns. The discrimination threshold of normal pigmented rats was a luminance level of -5.37+/-0.05 log cd/m(2); whereas the threshold level of 100-day-old RD rats was -1.14+/-0.09 log cd/m(2) with considerable variability in performance. When tested at a later age (about 150 days), the threshold level of RD rats was significantly increased (-0.82+/-0.09 log cd/m(2), p<0.03, paired t test). This apparatus could be useful to train rats at a very early age to distinguish between two different visual stimuli and may be effective for visual functional evaluations following therapeutic interventions. PMID- 17289152 TI - Monoamine oxidase (MAO) intron 13 polymorphism and platelet MAO-B activity in combat-related posttraumatic stress disorder. AB - BACKGROUND: The neurobiology of posttraumatic stress disorder (PTSD) involves alterations in multiple neuroendocrine and neurotransmitter systems. Platelet monoamine oxidase (MAO-B) has been associated with susceptibility to various psychiatric disorders, personality traits and behaviors. METHODS: Platelet MAO-B activity and MAO-B intron 13 polymorphism (a G/A substitution) were determined in male war veterans (n=106) with DSM-IV diagnosed current and chronic PTSD, divided into subgroups of PTSD patients with (n=28) or without (n=78) psychotic features, combat exposed veterans (n=41) who did not develop PTSD, and healthy control men (n=242). RESULTS: Two-way ANOVAs revealed a significant effect of diagnosis and smoking, a significant effect of smoking, no significant effect of genotype, and no significant interaction between genotype, smoking or diagnosis, on platelet MAO-B activity. One-way ANOVAs showed significantly lower platelet MAO-B activity in smokers than in nonsmokers. After controlling for smoking, veterans with psychotic PTSD had significantly higher platelet MAO-B activity than veterans with or without PTSD, or healthy subjects. LIMITATIONS: The results were obtained on peripheral biochemical marker, i.e. platelet MAO activity. CONCLUSIONS: The MAO-B intron 13 polymorphism was not functional, and did not affect platelet MAO B activity. The allele frequencies of the MAO-B genotype were similarly distributed among healthy controls and veterans with or without PTSD and/or psychotic symptoms. The results suggest that platelet MAO-B activity, controlled for smoking status, might be used as a peripheral marker of the psychotic symptoms in PTSD. PMID- 17289153 TI - Mismatch between self-reported quality of life and functional assessment in acute mania: a matter of unawareness of illness? AB - BACKGROUND: Studies addressing self-reported quality of life (QoL) in acute mania are scarce and inconsistent. While it has been suggested that there is some disagreement between objective measures and subjective QoL as reported by acutely manic patients, this issue has not been systematically studied. This study aims to investigate the self-reported QoL in manic, depressed, and euthymic BD subjects, as compared to matched healthy controls. METHODS: One-hundred and twenty type-I bipolar patients (40 manic, 40 depressed, and 40 euthymic) and 40 matched controls were studied. Self-reported QoL was assessed using the World Health Organization's Quality of Life Instrument-Short Version (WHOQOL-BREF). Objective functioning was assessed using the Global Assessment of Functioning (GAF), and depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale-17 items (HDRS) and the Young Mania Rating Scale (YMRS), respectively. RESULTS: Manic patients presented the lowest GAF measures but reported same overall QoL as euthymic patients and controls, and better QoL than depressed patients. Within the manic subgroup, there was a significant inverse correlation between psychological QoL and GAF scores (r=-0.54; p=0.001). LIMITATIONS: The cross-sectional design and the lack of control for potential comorbid conditions are the major limitations of the present study. CONCLUSIONS: Our findings suggest that this mismatch between objective and subjective measures during acute mania may be associated with a lack of insight or awareness of their own illness. PMID- 17289154 TI - L-thyroxine augmentation of serotonergic antidepressants in female patients with refractory depression. AB - BACKGROUND: Triiodothyronine (T3) augmentation in treatment-resistant depression had been successfully performed with both tricyclic as well as with SSRI antidepressants. In this paper, the efficacy of addition of moderate dose of l thyroxine (T4) to serotonergic antidepressants in refractory depression was evaluated. METHODS: The study included 17 female patients, aged 30-60 years, with treatment-resistant depressive episode in the course of unipolar or bipolar mood disorder. All patients had no history of thyroid axis disturbances and had T3, T4, and thyroid-stimulating hormone (TSH) values within the normal range. The antidepressants preceding thyroxine augmentation were serotonergic antidepressants (clomipramine - 11 patients, paroxetine - 5 patients, fluoxetine 1 patient). l-thyroxine was added in the dose of 100 microm daily for 4 weeks. RESULTS: After four weeks of l-thyroxine augmentation, the remission, assessed as 7 or less points on Hamilton Depression Rating Scale (HDRS) was obtained in eleven patients (64.7%). Five other patients (29.5%) had responded (reduction>50% on HDRS) and one patient did not show an improvement. The efficacy of augmentation did not show any correlation with laboratory tests' results performed before (T3, T4, TSH and TSH stimulation test) as well as with any clinical factors (age, diagnosis, duration of illness, duration of episode). CONCLUSIONS: The addition of moderate dose of l-thyroxine may be a successful augmentation strategy in female depressed patients in whom the effect of serotonergic antidepressant had been unsatisfactory. It may be efficient despite of the lack of disturbances of thyroid axis in such patients. PMID- 17289155 TI - Characteristics of smokers with a psychotic disorder and implications for smoking interventions. AB - Despite high rates of smoking among people with psychotic disorders, and the associated health and financial burden, few studies have investigated the characteristics of this group of smokers. This paper reports data from 298 smokers with an ICD-10 psychotic disorder residing in the community (56.7% with schizophrenia or schizoaffective disorder), including an examination of their demographic and clinical characteristics, smoking behaviours, severity of nicotine dependence, stage of change, and reasons for smoking and for quitting. Standardized self-report instruments were used, in conjunction with structured interviews, as part of the first phase of a randomized controlled trial. On average, participants smoked 30 cigarettes per day, commenced smoking daily at about 18 years of age (5 years before illness onset), and had made 2-3 quit attempts in their lifetime. Higher levels of nicotine dependence and concurrent hazardous use of alcohol or cannabis were associated with a younger age at smoking initiation. The present sample was also more likely to report stress reduction, stimulation and addiction as reasons for smoking, compared to a general sample of smokers. Males, precontemplators and participants with concurrent hazardous substance use cited fewer reasons for quitting smoking. These and other subgroup differences in smoking characteristics are used to illustrate potential implications for the nature and timing of smoking interventions among people with a psychotic disorder. PMID- 17289157 TI - Psychopathological and neuropsychological correlates of source monitoring impairment in schizophrenia. AB - Schizophrenic patients are known to show a deficit in the source monitoring function, which refers to the set of processes involved in the attribution of an origin to memories and beliefs. A failure in source monitoring was found to be associated with Schneiderian delusions in the recent literature. This study aimed to explore in a sample of schizophrenic patients and controls two aspects of the source monitoring process-recognition and source attribution- and their possible correlation with psychopathology and basic neuropsychological performances. A group of 45 stabilized schizophrenic patients and 54 normal volunteers were studied with a Source Monitoring Task and a battery of neurocognitive functions known to be disturbed in schizophrenia. Recognition of self-generated items was significantly worse than control values in Schneiderian delusional patients only, while source attribution of recognized self-generated items was significantly biased towards the external sources in all delusional patients in comparison to controls. Among schizophrenic patients, source misattribution of self-generated items was significantly correlated to an executive, planning performance. Both performances were correlated to verbal memory in controls. Results confirm an impairment of different subcomponents of source monitoring performance in schizophrenia, heterogeneously related to psychopathological features and neuropsychological performances known to be impaired in schizophrenia. PMID- 17289158 TI - Birth order effects on autism symptom domains. AB - Autism is predominantly genetically determined. Evidence supports familiality of the main sets of behavioral characteristics that define the syndrome of autism; however, possible non-genetic effects have also been suggested. The present study compared levels of autism symptom domains, as measured by the Autism Diagnostic Interview, and useful phrase speech scores between 106 pairs of first- and second born siblings from multiply affected families. In addition, the intercorrelations between the measures were compared between siblings. The overall mean repetitive behavior total score was significantly higher (worse) in first-born than in second-born siblings. In contrast, first-born siblings had significantly lower (better) useful phrase speech than their younger siblings. Autism social and non verbal communication scores were significantly correlated in first- and in second born siblings. However, there was a significant difference in the coefficients between first- and second-born siblings. Performance on the non-verbal communication domain was also significantly and positively correlated with useful phrase speech score in both first- and second-born siblings. It is unclear at this time whether these results are of biologic origin. Nevertheless, the findings suggest that genetic studies in autism using specific levels of familial autism traits as phenotypes should take into account their intercorrelations and birth order effects embedded in the instrument. PMID- 17289156 TI - Combined biological tests for suicide prediction. AB - Disturbances in serotonin neuroregulation and in hypothalamic-pituitary-adrenal axis activity are both likely, and possibly independent, factors in the genesis of suicidal behavior. This analysis considers whether clinically accessible measures of these two disturbances have additive value in the estimation of risk for suicide. Seventy-four inpatients with RDC major or schizoaffective depressive disorders entered a prospective follow-up study from 1978-1981, underwent a dexamethasone suppression test (DST) and had fasting serum cholesterol levels available in the medical record. As reported earlier, patients who had had an abnormal DST result were significantly more likely to commit suicide during follow-up. Serum cholesterol concentrations did not differ by DST result and low cholesterol values were associated with subsequent suicide when age was included as a covariate. These results indicate that, with the use of age-appropriate thresholds, serum cholesterol concentrations may be combined with DST results to provide a clinically useful estimate of suicide risk. PMID- 17289159 TI - Gene structure and transcription of IRF-1 and IRF-7 in the mandarin fish Siniperca chuatsi. AB - The genes of IRF-1 and IRF-7 have been cloned from the mandarin fish (Siniperca chuatsi). The IRF-1 gene has 4919 nucleotides (nt) and contains 10 exons and 9 introns, with an open reading frame (ORF) of 903nt encoding 301aa. The IRF-7 gene has 6057nt and also contains 10 exons and 9 introns, with an ORF of 1308nt encoding 436aa. The IRF-1 and IRF-7 genes have only one copy each in the genome. The transcription of IRF-1 and IRF-7 in different organs was analyzed by real time PCR, and both molecules were constitutively expressed. The IRF-1 and IRF-7 mRNAs were abundant in gill, spleen, kidney and pronephros. The temporal transcriptional changes for IRF-1, IRF-7 and Mx were investigated within 48h after poly I: C stimulation in liver, gill, spleen and pronephros. An increased transcription was detected for IRF-1 and IRF-7 12h post-stimulation, being earlier than the transcription of Mx protein; however, IRF-1 and IRF-7 transcription decreased while the Mx protein was stable at 48h post-stimulation. PMID- 17289160 TI - Analysis of antigen-stimulated B cell migration into germinal centers during the early stage of a T-dependent immune response. AB - The quasimonoclonal (QM) mouse provides a model to analyze B cell selection because major B cell antigen receptors (BCR) are composed of the knockin V(H)DJ(H) 17.2.25 (V(H)T) encoded H chain and the lambda1 or lambda2 L chain, thereby being specific for (4-hydoxy-3-nitrophenyl)acetyl (NP). We have reported that during a T-dependent antibody (Ab) response for a low-affinity NP analog p nitrophenylacetyl (pNP), although V(H)T/lambda1 and V(H)T/lambda2 IgM were equally produced, V(H)T/lambda2 IgG almost exclusively underwent affinity maturation toward pNP. The initial affinity of V(H)T/lambda2 B cells for pNP was approximately 50-100-fold higher than that of V(H)T/lambda1 B cells, suggesting a role of BCR affinity in recruiting B cells to affinity maturation processes. Here, we investigated whether the intensity of BCR signals could contribute to the selection of V(H)T/lambda2 B cells for affinity maturation. V(H)T/lambda2 B cells were more responsive to pNP than V(H)T/lambda1 B cells in vitro. When CFSE labeled QM B cells were transferred into the wild type mice where T cells had been primed with chicken gamma-globulin (CGG), QM B cells challenged by pNP conjugated CGG could be observed to get activated and migrate to GCs in the early phase of the T-dependent response to pNP-CGG. Adoptive transfer of sorted populations revealed that the V(H)T/lambda2 B cell population was more potent in migration into GCs than the V(H)T/lambda1 counterpart. Thus, it is suggested that the higher BCR affinity of V(H)T/lambda2 B cells may be an initial cue for their recruitment to GCs during a T-dependent Ab response. PMID- 17289161 TI - Toll-like receptor 2 and 4 combination engagement upregulate IL-15 synergistically in human rheumatoid synovial fibroblasts. AB - Toll-like receptors (TLRs) are pattern-recognition receptors that connect innate and adaptive immunity. Interleukin-15 (IL-15) is a proinflammatory, innate response cytokine that mediates pleiotropic effector functions in inflammatory synovitis of rheumatoid arthritis (RA). The aim of this study was to clarify whether stimulation of TLR2 and TLR4 by their specific ligands induces the production of IL-15 in fibroblast-like synoviocytes (FLS) from RA patients. FLS were isolated from RA synovial tissues and stimulated with the TLR2 ligand bacterial peptidoglycan (PGN) and the TLR4 ligand lipopolysaccharide (LPS). IL-15 in the culture supernatants was measured by ELISA, and mRNA levels were assessed by RT-PCR and real time PCR. The expression of TLR2, TLR4, and IL-15 in the RA synovium was quantified by immunohistochemistry and compared with values obtained in osteoarthritis synovium. IL-15 production increased in culture supernatants of RA FLS stimulated with PGN or PGN plus LPS, and this was upregulated at the transcriptional level. In contrast, LPS did not increase the level of IL-15 although it augmented the stimulatory effect of PGN on IL-15 production. Inhibition of nuclear factor (NF)-kappaB with a specific inhibitor abrogated the stimulatory effect of PGN or PGN plus LPS on IL-15. Neutralization of TLR2 with a blocking monoclonal antibody significantly reduced IL-15 production (P<0.05), reflecting the functional relevance of TLR2 activation in the induction of IL-15 production. These data suggest that TLR2 activation in RA FLS by microbial constituents is involved in the induction of IL-15 and that TLR2 promotes inflammation through NF-kappaB. TLR4 augmented the stimulatory effect of TLR2 on IL-15, possibly contributing to the maintenance of synovitis in patients with RA. PMID- 17289162 TI - A vitamin A deficient diet enhances proinflammatory cytokine, Mu opioid receptor, and HIV-1 expression in the HIV-1 transgenic rat. AB - The HIV-1 (HIV) transgenic (Tg) rat develops several immune abnormalities in association with clinical impairments that are similar to what are seen with HIV infection in humans. In HIV infection, retinoids and opioids can have separate and potentially combined effects on the clinical course of HIV disease. In these studies, the effects of a vitamin A deficient diet on T cell proinflammatory cytokine and mu opioid receptor (MOR) expression were examined in the Tg and in wild-type (WT) rats. The effects of the diet on HIV gene expression were also analyzed in the Tg rats. Phytohemagglutinin-stimulated T cells from WT rats on the vitamin A diet and from Tg rats on either diet were more likely to either produce increased percentages of T cells expressing intracytoplasmic IFN-gamma, secrete higher levels of TNF-alpha, and express higher levels of MOR mRNA and surface MOR. Mitogen stimulation also increased Tg rat HIV env, tat, and nef mRNA expression with even higher env and nef mRNA produced in association with the vitamin A deficient diet. All together, these data suggest that a vitamin A deficient diet can result in cellular effects that increase T cell proinflammatory responses and HIV expression, which may alter the course of disease in the HIV Tg rat model. PMID- 17289163 TI - The MHP36 line of murine neural stem cells expresses functional CXCR1 chemokine receptors that initiate chemotaxis in vitro. AB - Chemokines help to establish cerebral inflammation after ischemia, which comprises a major component of secondary brain injury. The CXCR4 chemokine receptor system induces neural stem cell migration, and hence has been implicated in brain repair. We show that CXCR1 and interleukin-8 also stimulate chemotaxis in murine neural stem cells from the MHP36 cell line. The presence of CXCR1 was confirmed by reverse transcriptase PCR and immunohistochemistry. Interleukin-8 evoked intracellular calcium currents, upregulated doublecortin (a protein expressed by migrating neuroblasts), and elicited positive chemotaxis in vitro. Therefore, effectors of the early innate immune response may also influence brain repair mechanisms. PMID- 17289164 TI - Regulation of IL-10 expression by upstream stimulating factor (USF-1) in glioma associated microglia. AB - Understanding the local CNS immune response to neoplasms is essential in the development of immune-based treatments for malignant brain tumors. Using rodent glioma models, we have recently found tumor-associated microglia/macrophages (MG/MP) to be less responsive to known MG/MP activators such as CpG, LPS and IFN gamma. To understand the mechanism of MG/MP suppression, nuclear extracts from rodent intracranial C6 gliomas, C6 glioma-associated MG/MP, normal brain, and normal MG/MP were obtained and studied using Electrophoretic Mobility Shift Assay (EMSA). Among the nuclear factors studied (AP-1, IRF, USF-1 and Stat-1) only USF 1, which is constitutively expressed in most cells, was down-regulated in tumor associated MG/MP, but not normal MG/MP. Because tumor-associated MG/MP had higher expression of IL-10 (but not TNF-alpha or TGF-beta), we evaluated the role of USF 1 on IL-10 expression. siRNA mediated inhibition of USF-1 expression in primary MG/MP cultures resulted in up-regulation of IL-10 mRNA but not TNF-alpha or TGF beta. These findings suggest that USF-1 may play a role in IL-10 regulation in MG/MP in brain tumors. PMID- 17289165 TI - Management of symptomatic tracheal pouches. AB - OBJECTIVE: Acquired tracheal pouches arise following tracheoesophageal fistula (TEF) repair, but are usually asymptomatic. Symptomatic tracheal pouches are rare, and the optimal management strategy debated. The evolution of our management to this challenging problem is presented. DESIGN: A case series over a 5-year period. SETTING: A tertiary care pediatric hospital. PATIENTS: Children with a past history of TEF repair in whom severity of pouch-related respiratory symptomatology warranted surgical intervention. MAIN OUTCOME MEASURES: Symptomatology, bronchoscopic findings, number and type of surgical interventions required, complications, and outcomes. RESULTS: Eleven patients required surgical intervention for a symptomatic tracheal pouch. Symptoms were due to stasis of secretions with associated pulmonary soiling in three children, severe tracheomalacia in six children, and respiratory obstruction related to the tip of a tracheotomy tube or endotracheal tube being displaced intermittently into the pouch in six children. Surgical management of the pouch included one fulguration with the CO(2) laser, one with microlaryngeal instruments, Bugbee cautery in two, open resection in one, and transcervical division in another. The final five children had endoscopic pouch division with Clickline biopsy forceps. All children have had resolution of their pouch-related symptoms, although two remain tracheotomy-dependent. CONCLUSIONS: Symptomatic tracheal pouches are rare. Surgical intervention to divide the common party wall between the trachea and the pouch may alleviate associated respiratory symptomatology. The Clickline biopsy forceps is a safe, rapid, and effective method of dividing a tracheal pouch. PMID- 17289166 TI - Effects of intra-accumbens NMDA and AMPA receptor antagonists on short-term spatial learning in the Morris water maze task. AB - Glutamatergic transmission within the nucleus accumbens (Nac) is considered to subserve the transfer of different types of information from the cortical and limbic regions. In particular, it has been suggested that glutamatergic afferences from the hippocampus and the prefrontal cortex provide the main source of contextual information to the Nac. Accordingly, several authors have demonstrated that the blockade of glutamate receptors within the Nac impairs various spatial tasks. However, the exact role of the different classes of glutamate receptors within the Nac in short-term spatial memory is still not clear. In this study we investigated the involvement of two major classes of glutamate receptors, NMDA and AMPA receptors, within the Nac in the acquisition of spatial information, using the Morris water maze task. Focal injections of the NMDA antagonist, AP-5 (0.1 and 0.15 microg/side), and the AMPA antagonist, DNQX (0.005, 0.01 microg/side), were performed before a massed training phase, and mice were tested for retention immediately after. NMDA and AMPA receptor blockade induced no effect during training. On the contrary, injection of the two glutamatergic antagonists impaired spatial localization during the probe test. These data demonstrate an involvement of the Nac in short-term spatial learning. Moreover, they prove that within this structure the short-term processing of spatial information needs the activation of both NMDA and AMPA receptors. PMID- 17289167 TI - Bioindicators and reproductive effects of prolonged 17beta-oestradiol exposure in a marine fish, the sand goby (Pomatoschistus minutus). AB - The effects of 17beta-oestradiol (E2) on mortality, growth rates, sexual maturation, hepatic vitellogenin (VTG) mRNA expression and reproductive success were investigated during an 8-month, water-borne exposure of a marine fish, the sand goby (Pomatoschistus minutus). Indicators of oestrogenic exposure were investigated as predictors of population-level reproductive success. E2 exposure concentrations were <5 (below limit of detection), 16+/-3, 97+/-20 and 669+/-151 ng l(-1) (bootstrap means and standard errors). The carrier solvent (<20 microl l(-1) propan-2-ol) significantly reduced the rate of egg production compared to untreated fish, but did not significantly affect male VTG mRNA expression, brood size, or the other studied parameters. Fish exposed to 16 ng l(-1) E2 showed few adverse effects compared with solvent only-exposed fish. Exposure to 97 ng l(-1) E2 significantly inhibited male sexual maturation, induced male VTG mRNA expression and delayed spawning. The 97 ng l(-1) E2 exposed population also produced fertile eggs at a significantly slower rate than solvent controls; however, brood size, fertility and overall reproductive success were not significantly affected. Exposure to 669 ng l(-1) E2 significantly increased mortality, adversely affected haematological parameters and caused an almost total lack of reproductive activity, with both sexes failing to mature. Reproductive failure following exposure to 669 ng l(-1) E2 was evident in both sexes when crossed with untreated animals. This work indicates that marine fish are similarly as sensitive to oestrogenic exposure as freshwater fish, that exposure biomarkers such as VTG are more sensitive to exposure than are reproductive effects, and that the use of carrier solvents in long-term reproductive studies should be avoided. PMID- 17289168 TI - The effects of anti-bacterials on the malaria parasite Plasmodium falciparum. AB - Many anti-bacterial drugs inhibit growth of malaria parasites by targeting their bacterium-derived endosymbiotic organelles, the mitochondrion and plastid. Several of these drugs are either in use or being developed as therapeutics or prophylactics, so it is paramount to understand more about their target of action and modality. To this end, we measured in vitro growth and visualized nuclear division and the development of the mitochondrion and apicoplast in Plasmodium falciparum treated with five drugs targeting bacterial housekeeping pathways. This revealed two distinct classes of drug effect. Ciprofloxacin, rifampicin, and thiostrepton had an immediate effect: slowing parasite growth, retarding organellar development and preventing nuclear division. Classic delayed-death, in which the drug has no apparent effect until division and reinvasion of a new host by the daughter merozoites, was only observed for two drugs: clindamycin and tetracycline. These cells had apparently normal division and segregation of organelles in the first cycle but severe defects in apicoplast growth, subtle changes in the mitochondrion and a failure to complete cytokinesis during the second cycle. In two cases, the drug response in P. falciparum directly conflicted with reported responses for the related parasite Toxoplasma gondii, suggesting significant differences in apicoplast biology between the two parasites. PMID- 17289169 TI - Cryptosporidium parvum spermidine/spermine N1-acetyltransferase exhibits different characteristics from the host enzyme. AB - Cryptosporidosis is a severe opportunistic infection of immuno-compromised individuals for which no reliable therapy exists. The parasite scavenges host derived polyamines, particularly spermine, which is then converted to the lower polyamines by the combined action of spermidine/spermine N(1)-acetyltransferase (SSAT) and polyamine oxidase (PAO). We have isolated and expressed the Cryptosporidium parvum SSAT for kinetic and molecular comparison with the host enzyme. The CpSSAT is a homotetramer with a subunit molecular mass of 18 kDa and low sequence similarity to higher eukaryotes but maintains the critical arginine residues in the active site. The CpSSAT had an activity of 299 nmol(-1)min(-1)(mg of protein)(-1) and exhibits an ordered Bi-Bi kinetics with preferred substrate specificity for spermine. Polyamine analogues having unsaturated central carbons were found to exhibit mixed inhibition kinetics of the CpSSAT. The cis-analogues were more effective inhibitors of the CpSSAT with lower K(i) values than the trans-analogues. Experiments aimed at determining the ratio of the time of the analogue in the enzyme active site to that spent out (in-out time: delta ln E/deltat) confirmed the higher efficiency of the cis-analogues as inhibitors of the CpSSAT. The results of this study reveal that the C. parvum SSAT may provide a rational target for drug design. PMID- 17289170 TI - Neurotensin receptor binding and neurotensin-induced growth signaling in prostate cancer PC3 cells are sensitive to metabolic stress. AB - Neurotensin (NT) stimulates the proliferation of prostate cancer PC3 cells, which express high levels of its G protein-coupled receptor NTS1. To shed light on mechanisms that might serve to coordinate mitogenic responses to metabolic status, we studied the effects of metabolic inhibitors on NTS1 function. We also related these effects to cellular ATP levels and to the activation of AMP activated protein kinase (AMPK). Glycolytic and mitochondrial inhibitors, at concentrations that reduced cellular ATP levels, altered NT binding to the cells, inhibited NT-induced inositol phosphate formation, and inhibited NT-induced DNA synthesis. For eight of the nine inhibitors, the potencies to alter NT receptor function correlated to the potencies to decrease cellular ATP levels. In keeping with its known role to oppose metabolic stress, AMPK was activated by the metabolic inhibitors. Accordingly, the AMPK activator AICAR elevated cellular ATP levels and produced effects on NTS1 function that were opposite to those for the metabolic inhibitors. These results indicate that metabolic stress inhibited NTS1 function by a mechanism that involved a fall in cellular ATP levels and that was opposed by activation of AMPK. In a broader context, these findings are compatible with the idea that one means by which cells might coordinate mitogenic signaling to metabolic status could involve changes in growth factor receptor function. PMID- 17289171 TI - Discordant expression of pro-B-type and pro-C-type natriuretic peptide in newborn infants of mothers with type 1 diabetes. AB - BACKGROUND: Maternal diabetes increases the risk of hypertrophic cardiomyopathy in the fetus. As signaling via the C-type natriuretic peptide (CNP) specific receptor protects against cardiac hypertrophy, we examined whether maternal type 1 diabetes affects the plasma concentrations of proCNP-derived peptides in newborn infants. METHODS: Plasma concentrations of proCNP-derived peptides were measured in umbilical cord plasma and human placental tissue extracts using sequence-specific radioimmunoassays raised against N-terminal and C-terminal proCNP regions, respectively. RESULTS: The median proCNP concentrations were similar in umbilical cord plasma from pregnant women with and without type 1 diabetes (17 pmol/L vs. 19 pmol/L, P not significant) and did not correlate with the proBNP concentrations in the same samples. However, the molar ratio between the proCNP and the CNP peptide was increased in umbilical cord plasma compared to adult plasma (4.6 vs. 1.1), which parallels our earlier findings for proBNP and BNP peptides. CONCLUSIONS: There is a discordant expression of CNP and BNP peptides in newborn infants of mothers with diabetes. Moreover, fetal metabolism of proCNP and CNP appears to differ from healthy adults. The precise mechanism underlying these differences warrants further investigation. PMID- 17289172 TI - ProANP and NT-proBNP levels to prospectively assess cardiac function in breast cancer patients treated with cardiotoxic chemotherapy. AB - BACKGROUND: Cardiac function impairment is a known side effect of epirubicin based chemotherapy. Activation of natriuretic peptides is demonstrated in patients with heart failure. AIMS: To identify prospectively the cardiotoxic profile of epirubicin-based chemotherapy in breast cancer patients and to evaluate the sensitivity of proANP and NT-proBNP as early biochemical markers of cardiac dysfunction. METHODS: Forty cancer patients divided in two nonrandomized groups received either epirubicin and paclitaxel (Group A, n=26) or mitoxantrone and docetaxel (Group B, n=14). Control groups, Group C (n=13) and Group D (n=20), consisted of female patients with heart failure and healthy women respectively. Natriuretic peptides and LVEF were determined in all patients. RESULTS: A statistically significant difference was recorded regarding LVEF before and after treatment in Group A patients (p=0.0001). Three patients had a significant LVEF decline between 10% and 18% from baseline values, while three reached an LVEF value below 50%. All of them presented an increase in proANP and NT-proBNP values (mean increase 270.31+/-124 fmol/ml and 303.57+/-108 fmol/ml, respectively). A significant correlation between the increase in plasma proANP (r=0.8, p<0.0001), as well as NT-proBNP (r=0.7, p<0.0001) and the decrease in LVEF was observed. Regarding Group A, levels of proANP increased from 192.25 fmol/ml before treatment to 287.84 fmol/ml after treatment (p=0.0001), whereas NT-proBNP increased from 152.50 to 242 fmol/ml (p<0.0001) respectively. During follow up, two Group A patients developed congestive heart failure twelve and fourteen months after the completion of chemotherapy respectively. A significant LVEF decline was recorded in both patients during the episode. Regarding Group B, no statistically significant differences were demonstrated. CONCLUSION: ProANP and NT-proBNP levels might be used as reliable and sensitive markers in the detection of early cardiac impairment caused by epirubicin-based chemotherapy. PMID- 17289173 TI - Impact of postprocedure minimum stent area on long-term results following abciximab-coated stent implantation: an intravascular ultrasound analysis. AB - BACKGROUND: Smaller postprocedural minimum stent areas (MSA) measured by intravascular ultrasound (IVUS) have been associated with higher restenosis rates. METHODS: This was a single-center, prospective, randomized trial and we assessed the predictive value of MSA for long-term patency and the incidence and extent of incomplete stent apposition (ISA) following abciximab-coated stent (n=69) compared to bare metal stent (BMS) implantation (n=69). All patients underwent IVUS follow-up at 6 months. RESULTS: At follow-up coronary angiogram, the restenosis rate and late loss were 12%, 0.30+/-0.24 mm in abciximab-coated stent group and 29%, 0.68+/-0.36 mm in BMS group (p=0.011, 0.010, respectively). At follow-up IVUS, intrastent lumen area was significantly larger and intrastent neointimal hyperplasia area was significantly smaller in abciximab-coated stent group than those in BMS group (5.9+/-1.6 mm(2) vs. 4.5+/-1.7 mm(2), p=0.001, and 1.9+/-1.5 mm(2) vs. 3.3+/-1.9 mm(2), p<0.001, respectively). Target lesion revascularization occurred in 9%, 0%, and 0% in abciximab-coated stent group and 19%, 4%, and 1% in BMS group in lesions with a MSA <6.0 mm(2), from 6 to 7.5 mm(2), and >7.5 mm(2), respectively. Late-acquired ISA at follow-up was observed in 7 patients and there was no difference in the incidence of ISA between both groups [abciximab-coated stent: n=3 (4%) vs. BMS: n=4 (6%), p=0.698]. CONCLUSION: Abciximab-coated stent reduced restenosis and had a considerably lower optimal MSA threshold compared to BMS and showed lower incidence of late-acquired ISA. PMID- 17289174 TI - Negative association between serum levels of matrix metalloproteinases-2 and -9 and aortic stiffness in healthy adults. AB - BACKGROUND: Arterial stiffness is a marker of cardiovascular disease and independent predictor of cardiovascular risk. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade components of the extracellular matrix, which is an important determinant of the arterial elastic properties. This study sought to investigate the association between MMP-2 and MMP-9 (gelatinase A and B respectively) and arterial stiffness in healthy human subjects. METHODS: A total of 213 apparently healthy subjects (mean age 41 years, range 18 to 60, 141 males and 72 females) were studied. Carotid-femoral pulse wave velocity (PWV) and aortic augmentation index (AIx) were measured as indices of aortic stiffness and wave reflections respectively. Associations with serum levels of total MMP-2, total MMP-9 and high-sensitivity C-reactive protein (hsCRP) were evaluated with multiple regression models. RESULTS: In these models, PWV exhibited a significant negative association with both MMP-2 (standardized b= 0.177, P=0.003) and MMP-9 (b=-0.122, P=0.032), after controlling for potential confounding factors such as age, gender, blood pressure, heart rate, body-mass index, smoking habits (pack-years), blood glucose, total cholesterol, and level of subclinical inflammation expressed by hsCRP (adjusted R2 of models 0.352 and 0.338 respectively). On the other hand, no relationship between MMP-2 or MMP-9 and AIx was found. CONCLUSIONS: Circulating MMP-2 and MMP-9 are inversely associated with large artery stiffness but not with wave reflections in healthy persons. This finding implies that these gelatinases may have a possible role in the determination of arterial function and has potential implications for their involvement in the pathophysiology of cardiovascular diseases. PMID- 17289175 TI - Value of VDD-pacing systems in patients with atrioventricular block: experience over a decade. AB - BACKGROUND: Even though current guidelines suggest the use of VDD pacemakers in patients with AV block and normal sinus node function, a DDD system is often preferred for fear of either long-term atrial undersensing or late sinus node dysfunction and the resultant need for system upgrades. METHODS: We evaluated the long-term follow-up of all VDD pacemakers implanted in our center between 1992 and 2001 regarding atrial sensing, maintenance of AV synchrony, incidence of atrial fibrillation (AF), or the need for system upgrade, respectively. RESULTS: 320 consecutive patients (56% men, age 75+/-13 years) received a VDD pacemaker for the following indications: third-degree AV block 54%, second-degree AV block 34%, fascicular block with first-degree AV block and syncope 6%, others 6%. 138 patients (43%) died during follow-up, 3.8+/-2.3 years after implantation. Follow up duration was 6.1+/-2.5 years in the remaining patients. At the last follow-up, 268 pacemakers (84%) were programmed to the VDD mode, 47 pacemakers (15%) were permanently programmed to the VVI mode (AF 36, undersensing 7, others 4, respectively). In five patients a DDD upgrade was necessary for sinus node dysfunction (3) or lead defect (2). Lead revision was performed in 19 patients (6%) (ventricular lead dislocation 7, atrial undersensing 6, lead fracture 3, others 2, respectively). CONCLUSION: VDD pacemakers have an excellent long-term performance in patients with AV block. They have a very low incidence of lead revisions for atrial undersensing (2%) and DDD upgrades for secondary sinus node dysfunction (1%). PMID- 17289177 TI - Accelerated streptokinase in ST-elevation myocardial infarction--a Romanian (ASK ROMANIA) multicenter registry. AB - BACKGROUND: The classical streptokinase regimen (1.5 M.U. over 60 min) may be too slow in patients with ST-elevation myocardial infarction (STEMI). OBJECTIVE: To compare the efficacy and safety of four streptokinase regimens in STEMI patients. METHODS: 1880 consecutive patients admitted within 6 h of STEMI onset were allocated one of the following four streptokinase regimens: 1.5 M.U. over 60 min (n=517); 1.5 M.U./30 min (n=355); 1.5 M.U./20 min (n=507); 0.75 M.U./10 min, repeated or not after 50 min if no electrocardiographic criteria of reperfusion (n=501). RESULTS: Rates of coronary reperfusion (non-invasively detected) for SK1.5/30 (72.39%), SK1.5/20 (75.34%) and SK0.75/10 (72.85%) were similar and higher than for SK1.5/60 (64.03%, p=0.019, p<0.0001, and p=0.006, respectively). In-hospital mortality was significantly lower for SK1.5/20 (7.10%) and SK0.75/10 (7.38%) and at the limit of significance for SK1.5/30 (7.60%) compared with SK1.5/60 (11.60%, p<0.0001, 0.006, and 0.053, respectively). Intracerebral haemorrhage and other major bleeding had similar incidence in the four groups. CONCLUSIONS: Compared to the classical 1.5 M.U. over 60 min streptokinase regimen, significantly higher rates of coronary reperfusion and lower in-hospital mortality can be obtained by infusing the same dose over only 20 min, or either one or two half doses over only 10 min, without risk increase. PMID- 17289176 TI - Angiographic and intravascular ultrasound study of the effects of overlapping sirolimus- and paclitaxel-eluting stents: comparison with same drug-eluting overlapping stents. AB - BACKGROUND: Although complete coverage of diffuse long coronary lesions has warranted the use of overlapping drug-eluting stents (DESs), the effect of stent overlap with different DESs on the neointimal hyperplasia and whether it would result in dose-related side effects are unknown. METHODS AND RESULTS: Forty-seven consecutive patients, from June 2003 to August 2004, underwent percutaneous coronary intervention (PCI) with 2 of the same or different overlapping DESs for diffuse long lesions. Out of the total of 47 patients, a nine-month angiographic examination and IVUS were performed in 40 (85.1%) patients. Of the 47 overlapping DESs utilized, 14 were overlapped using sirolimus- and paclitaxel-eluting stents (S-P group), 13 using two sirolimus-eluting stents (S-S group) and 20 using two paclitaxel-eluting stents (P-P group). In the follow-up, there was no difference between the three groups in the late loss or area of neointimal hyperplasia. All restenoses were noted at non-overlapping sites (2 at the proximal edge of the proximal stent, and 3 at the distal in-stent). There were no stent thromboses documented or aneurysmal formations at the overlapping site in any of the three groups. One late stent malapposition was observed not at an overlapping site, but in the distal single stent area. CONCLUSIONS: In conclusion, compared with using the same overlapping DESs, PCI with different overlapping DESs exhibited similar effects on the suppression of neointimal hyperplasia and did not increase the side effects of the DES. PMID- 17289179 TI - Isolated cleft of the posterior mitral valve leaflet. PMID- 17289178 TI - Accuracy of bedside tissue Doppler echocardiography for the prediction of in hospital mortality in elderly patients with acute heart failure with preserved left ventricular systolic function. comparison with B-type natriuretic peptide measurement. AB - According to recent studies, tissue Doppler echocardiography used as a non invasive surrogate for left ventricular diastolic pressures regardless of rhythm is likely to offer additional information beyond the clinical judgment and the B type natriuretic peptide (BNP) assay in the emergency diagnosis of acute heart failure with preserved left ventricular systolic function (HFPSF). The present study attempted to determine the usefulness of bedside tissue Doppler echocardiography as compared with BNP, both obtained at presentation before unloading therapy, for the prediction of in-hospital outcome in 75 consecutive elderly patients with acute HFPSF, of whom 16 died during their in-hospital stay. Unlike BNP (p=0.002), the spectral tissue Doppler-derived E/Ea ratio was not able to provide prognostic information in such patients before tailored therapy (p=0.9). PMID- 17289180 TI - Quibus cor palpitet: hyena cor. AB - The search for a genuine thought in ancient times makes medical archeology part of our contemporary knowledge, not to say a patrimony to be harbored. A Roman encyclopedia is a compilation of the prevailing knowledge of scientific and medical matters at the time. In this paper an original Roman prescription for a specific cardiac complaint is analyzed for its activity and efficaciousness. Further investigation of the effect of Selenium administration is warranted. PMID- 17289181 TI - Transient left ventricular apical ballooning syndrome (takotsubo cardiomyopathy) as a complication of permanent pacemaker implantation. AB - BACKGROUND: Takotsubo cardiomyopathy is a rare and newly described clinical entity characterized by transient left ventricular apical ballooning and left ventricular apical dyskinesis in the absence of angiographic evidence of significant coronary vessel disease found predominantly in post-menopausal women. It was first documented in the USA in 2004, and it has previously been described only in Japanese and Caucasian patients. CASE REPORT: A 77-year-old Native Hawaiian woman was admitted to the hospital for severe bradycardia. To the best of our knowledge, this is the first time that normal ventricular function has been documented by echocardiography just prior to the development of the syndrome of transient left ventricular apical ballooning. METHODS: Retrospective review of the reported patient's medical record, cardiac angiography and ventriculography, echocardiography, and ECGs. DISCUSSION: The patient reported manifested all of the diagnostic criteria for transient left ventricular apical ballooning syndrome proposed by the Mayo Clinic. The finding of normal cardiac morphology and contractility by echocardiography two days prior to diagnosis shows that this syndrome develops rapidly. The case reported here is the first time that transient left ventricular apical ballooning syndrome has been documented in a Native Hawaiian patient in a tropical location, suggesting that transient left ventricular apical ballooning likely occurs across all ethnic and geographical lines. PMID- 17289182 TI - A 45-year-old woman with fibromuscular dysplasia and celiac disease. PMID- 17289183 TI - Successful percutaneous treatment of anomalous left coronary artery from pulmonary artery. AB - Anomalous origin of the left main coronary artery from the pulmonary artery (ALCAPA) is an uncommon congenital condition seen in the adult population, with most patients developing symptoms in infancy. We describe successful closure of an ALCAPA in an adult using a percutaneous transcatheter approach in a patient with evidence of anterior wall ischemia believed to be the consequence of myocardial steal. A 30-year-old female was noted to have continuous flow in the right ventricular septum on transthoracic echocardiography, with subsequent imaging confirming the presence of an ALCAPA. Myocardial perfusion imaging confirmed anterior wall ischemia, and as a strategy to optimize coronary perfusion pressure, the patient underwent percutaneous ALCAPA closure using an Amplatzer vascular plug. The procedure was well tolerated, with no evidence of anterior ischemia or myocardial dysfunction. Follow up perfusion imaging demonstrated no residual anterior wall ischemia. Transcatheter closure of an ALCAPA is a potentially safe and effective alternative treatment strategy in this patient population. PMID- 17289185 TI - The association of hoof lesions at claw trimming with test-day milk yield in Danish Holsteins. AB - In a cross-sectional study, performed between October 2002 and April 2003 on 55 Danish dairy herds with 6161 predominantly Holstein Friesian cows the prevalence of 9 hoof lesions was determined. All test-day yields (TDY) of kg energy corrected milk (ECM) in the lactation of diagnosis were recorded. For the purpose of including hoof lesions in a decision support model an attempt was made to aggregate the lesions into digital dermatitis (DD), other interdigital diseases (OID, infectious diseases other than DD) and hoof horn diseases (HHD, related to metabolic disorders and trauma). A division was made based on the stage of lactation in which the lesions were diagnosed; during the first 100 days in milk, between days 101 and 200 and between days 201 and 305. Associations between the presence of hoof lesions at trimming and milk production were analyzed by linear mixed modeling at the cow level, clustered within herd. The data of primiparous cows was analyzed separately from the multiparous cows. Based on the associations between TDY and the individual lesions aggregated into HHD, this aggregation as initially planned could not be justified and was therefore not maintained. For OID the value of early diagnosis was apparent; an early diagnosis and early treatment (<101 DIM) was associated with either a positive value or a value less negative compared to a diagnosis and treatment in late lactation (201-305 DIM). This pattern was not as clearly present for the other lesions. PMID- 17289184 TI - NT-proBNP concentrations indicate cardiac disease in pediatric patients. AB - OBJECTIVE: To test the performance of N-terminal pro B-type natriuretic peptide to distinguish from cardiac and non-cardiac disease in the pediatric patient population. METHOD: NT-proBNP concentrations were retrospectively analysed in 102 pediatric patients (median age: 5.96 years; 0-18 years) with cardiac diseases comprising left-to-right-shunt lesions (n=42), left heart lesions (n=47) and right heart lesions (n=13) and in 65 pediatric patients (median age: 3.37 years; 0.03-18 years) with acute infection, minor trauma or neurological disorder. RESULTS: NT-proBNP levels between patients without heart disease and patients with heart disease differed significantly with a median NT-proBNP value of 224.9 ng/l, 108.7 ng/l-945.6 ng/l (25th-75th percentile) versus 76.7 ng/l, 35.0 ng/l 122.4 ng/l, p<0.0001. The diagnostic performance of NT-proBNP to differentiate between patients with and without cardiac diseases was high with an area under curve of 0.81 (95% confidence intervals 0.75-0.87). At a cut-off value of 134 ng/l the specificity was 83% (95% CI: 74-92%). The presence of heart failure (p<0.0001) had a significant impact on NT-proBNP concentrations. CONCLUSIONS: NT proBNP measurement is a helpful addition to identify pediatric patients with heart disease. PMID- 17289186 TI - Primary physician services-list size and primary physicians' service production. AB - The regular general practitioner scheme was introduced in Norway in 2001. A patient list system in combination with a partial per capita financing system for primary physician services was then introduced. The focus of this research was to study how the patient list system influences patients' accessibility to primary physicians, and how the system influences primary physicians' service production. We studied two possibilities: First, some physicians can have an incentive to acquire a long patient list in order to ensure a high unearned income from per capita payment. This can lead to rationing of consultations. Second, physicians with short lists can have an incentive to increase their service production per consultation in order to compensate for lack of income. This leads to increased costs. The research questions were investigated empirically using two large sets of national data. Two of the main findings were that long lists do not lead to rationing, and short lists do not increase service production per consultation. PMID- 17289187 TI - The long-term health and economic consequences of the 1959-1961 famine in China. AB - This paper, using a difference-in-differences method, tries to quantify the long term effects of China's 1959-1961 famine on the health and economic status of the survivors. We find that the great famine caused serious health and economic consequences for the survivors, especially for those in early childhood during the famine. Our estimates show that on average, in the absence of the famine, individuals of the 1959 birth cohort would have otherwise grown 3.03 cm taller in adulthood. The famine also greatly impacted the labor supply and earnings of the survivors with famine exposure during their early childhood. PMID- 17289188 TI - Staining of Chlamydia trachomatis elementary bodies: a suitable method for identifying infected human monocytes by flow cytometry. AB - Persistence of Chlamydia trachomatis (C. trachomatis) in the joint is the most frequent cause of reactive arthritis following urogenital tract infection. The resulting changes of host cell antigen- and cytokine-expression are not precisely understood. We developed and evaluated a direct cytometric approach to visualize in vitro C. trachomatis-infected monocytes. Infectious elementary bodies (EBs) of C. trachomatis serovar K were labelled by incubation with 5-(and-6) carboxyfluorescein diacetate succinimidyl ester (CFSE). Afterwards, human peripheral blood monocytes were cultured with the CFSE-labelled EBs and analysed by flow cytometry. Real-time polymerase chain reaction (PCR) was used to demonstrate intracellular uptake and viability of CFSE-labelled C. trachomatis by the determination of gene expression. Labelling EBs with CFSE may become a valuable tool for studying the interaction between C. trachomatis and the host cell. PMID- 17289189 TI - Archaeal diversity and community structure in a Swedish barley field: Specificity of the EK510R/(EURY498) 16S rDNA primer. AB - The aim of this study was to analyze a total euryarchaeal community at DNA and RNA levels in a Swedish barley field with relation to soil depth (0-10 and 20-30 cm layers), soil fraction (bulk soil and rhizosphere) and time (August and November sample collection). Amplification of 16S rRNA gene using the archaeal universal A2F and Euryarchaea specific EK510R/(EURY498) primer pair, combined with denaturing gradient gel electrophoresis (DGGE), revealed distinct differences between rDNA and rRNA DGGE profiles. The soil depth, time, or rhizosphere effects did not significantly influence Archaeal community structure. Surprisingly, sequence analysis of DGGE-derived amplicons revealed the presence of Euryarchaea as well as uncultured soil Crenarchaea affiliated with group 1. In agreement, sequence comparison analyses showed that the majority of uncultured Crenarchaea group 1 had almost 100% sequence complementarity to the 3' end of the EK510R/(EURY498) primer. Therefore, we propose that EK510R/(EURY498R) is a universal archaeal primer rather than a Euryarchaea specific SSUrRNA primer. Hence, considerable care should be taken during application of this primer in studies of euryarchaeal biodiversity in soil environments. PMID- 17289190 TI - On-line monitoring of changes in host cell physiology during the one-step growth cycle of Bacillus phage Bam35. AB - In this study an on-line electrochemical method was developed to examine the one step growth cycle (OSGC) of the bacteriophage Bam35. The on-line conditions for monitoring the OSGC and the effect of aeration on the duration of the OSGC were defined. The data indicate that binding of phenyldicarbaundecaborane anions to Bacillus thuringiensis cells infected with Bam35 can be used as a sensitive indicator of cell lysis. PMID- 17289191 TI - Rapid identification of gelatin and casein hydrolysis using TCA. AB - Using TCA as the developing agent we have identified the hydrolysis of gelatin and casein within 3 h. When compared with conventional gelatin and casein hydrolysis techniques we have found the results of the TCA enhancement to be more rapid and sensitive than the conventional methods. PMID- 17289192 TI - Anterior EEG asymmetries and opponent process theory. AB - The opponent process theory of emotion [Solomon, R.L., and Corbit, J.D. (1974). An opponent-process theory of motivation: I. Temporal dynamics of affect. Psychological Review, 81, 119-143.] predicts a temporary reversal of emotional valence during the recovery from emotional stimulation. We hypothesized that this affective contrast would be apparent in asymmetrical activity patterns in the frontal lobes, and would be more apparent for left frontally active individuals. The present study tested this prediction by examining EEG asymmetries during and after blocked presentations of aversive pictures selected from the International Affective Picture System (IAPS). 12 neutral images, 12 aversive images, and 24 neutral images were presented in blocks. Participants who were right frontally active at baseline did not show changes in EEG asymmetry while viewing aversive slides or after cessation. Participants left frontally active at baseline, however, exhibited greater relative left frontal activity after aversive stimulation than before stimulation. Asymmetrical activity patterns in the frontal lobes may relate to affect regulatory processes, including contrasting opponent after-reactions to aversive stimuli. PMID- 17289193 TI - Walking patterns change rapidly following asymmetrical lower extremity loading. AB - The purpose of this study was to determine the amount of time needed for individuals to become well accommodated to asymmetrical changes in lower extremity inertial properties. Participants walked at 1.57 m s(-1) during four separate data collection sessions over the period of eight days. On days 1 and 7, participants completed a 60 min treadmill protocol consisting of both overground (motion and ground reaction force recorded) and treadmill (vertical ground reaction force recorded) walking. On day 1, 1.95 kg was attached distally to one shank prior to the start of the 60 min treadmill protocol and was not removed until day 7. On day 7, the load was permanently removed prior to the 60 min treadmill protocol. On days 2 and 8 participants completed three overground walking trials and walked on the treadmill for approximately 5 min. Stance and swing time asymmetries appeared immediately and were complete following initial assessment after the load was attached. Net joint moments at the knee and hip were altered and continued to change beyond initial exposure to the load, but these changes were complete within 5 min. Overall, results suggest that changes in walking symmetry due to asymmetrical lower extremity loading are immediate and complete within 5 min of exposure to the load. We recommend that at least 5 min of walking or other normal activity be used to accommodate individuals to novel asymmetrical lower extremity loading. PMID- 17289195 TI - Is optimal vision required for the successful execution of an interceptive task? AB - The importance of optimal visual function in demanding interceptive tasks is far from established. The aim of the study was to determine whether induced myopic blur and hence sub-optimal visual function would give rise to a detrimental effect on performance in the execution of an interceptive task. The batting performance of grade level cricket players was assessed facing a bowling machine whilst wearing contact lenses of four different refractive conditions (plano (nil), +1.00, +2.00 and +3.00D over-refraction), inducing increasing amounts of myopic blur. Performance for each condition was assessed based both on the shot quality against each delivery judged by a qualified cricket coach blind to each condition, along with an evaluation of the quality of ball-bat contact for each delivery. No significant change was found in batting performance with the introduction of +1.00 and +2.00D of induced myopic blur. A +3.00D over-correction was required before any significant decrease in batting performance was detected, demonstrating that batters needed to be essentially legally blind (as simulated through the use of the +3.00D over-refraction) before there was any significant measurable decrement in batting performance. We concluded that optimal visual correction is not necessarily required for optimal performance in a demanding interceptive task, and that the human perceptual-motor system is capable of compensating for marked alterations in input. PMID- 17289194 TI - Velocity discrimination: reliability and construct validity in older adults. AB - The aim of this study was to determine whether a test of velocity discrimination is a reliable and valid measure of proprioception in healthy older adults. Results revealed excellent test-retest reliability over a 2-week period. Velocity discrimination also indicated good construct validity with modest correlations with center of pressure sway outcomes in eyes open and closed conditions as well as stair climbing time. Good construct validity was identified by velocity discrimination sensitivity to age with a higher mean value for the older participants than for the younger participants. These findings suggest velocity discrimination is a valid and reliable measure of velocity sense, which may be included with measures of position and movement sense to enhance the proprioceptive testing repertoire among researchers. Implications of these results are discussed in terms of evaluation of proprioceptive training programs aimed to enhance postural control. PMID- 17289196 TI - Memory performance of hypercholesterolemic mice in response to treatment with soy isoflavones. AB - The aim of this study is to investigate the memory performance of hypercholesterolemic mice in response to soy isoflavones (SI) treatment and the mechanism involved. In this study, 64 mice were randomly divided into four groups: control, high lipid diet without SI, high lipid diet with a low SI level (50 mg/kg bw) and high lipid diet with a high SI level (100 mg/kg bw). The experimental period was 30 days. The results indicated that the mice given the different treatments showed the different percentages of good, medium and poor memory performance. chi(2) analysis revealed significant difference in memory performance (P<0.05) between the high lipid diet without SI group and the high lipid diet with a low SI level group or high lipid diet with a high SI level group. Moreover, SI treatment resulted in a decrease in blood cholesterol (TC) level (high lipid diet without SI group versus high lipid diet with a low SI level group or high lipid diet with a high SI level group, P<0.05) and triglyceride (TG) level (high lipid diet without SI group versus high lipid diet with a low SI level group or high lipid diet with a high SI level group, P<0.05). In addition, SI treatment resulted in a significant decrease in acetylcholinesterase (AChE) activity and significant increases in glutamic acid and aspartic acid contents in the frontal cerebral cortex and hippocampus. The results suggest that SI improve the memory performance of hypercholesterolemic mice, and the mechanism underlying the improvement might closely correlate with its roles in decreasing high blood lipid levels and modulating the metabolism of neurotransmitters such as acetylcholine and amino acids in brain areas of hypercholesterolemic mice. PMID- 17289197 TI - Antibiotic resistance and Caco-2 cell invasion of Pseudomonas aeruginosa isolates from farm environments and retail products. AB - The potential pathogenicity of Pseudomonas aeruginosa isolates from food animals, retail meat products, and food processing environments was evaluated by determining their antibiotic resistance profiles and invasiveness into human intestinal Caco-2 cell. In general, the genomically diversified isolates of P. aeruginosa were resistant to beta-lactams (ampicillin, amoxicillin-clavulanic acid, cefoxitin, ceftiofur, and cephalothin), chloramphenicol, tetracycline, kanamycin, nalidixic acid, and sulfamethoxazole-trimethoprim. Acquisition of any other antibiotic resistance genes, such as class 1 integrons and other beta lactamase genes, was not found in the tested isolates. The expression of OprM membrane protein, which is associated with a multidrug efflux system, played a major role in their antibiotic resistance. Single mutation in the GyrA to confer resistance to nalidixic acids was also found in the tested isolates, indicating that these factors could synergistically affect the resistance of the P. aeruginosa isolates. The number of bacteria invading into the Caco-2 cells was 2.5 log(10) CFU/ml on average. Therefore, the public health concern of P. aeruginosa could be relevant since its occurrence in food animals could cross contaminate the retail meat products during food handling and processing. PMID- 17289198 TI - Characterization of the gene encoding the 16S rRNA of Enterobacter sakazakii and development of a species-specific PCR method. AB - The gene encoding the 16S rRNA of Enterobacter (E.) sakazakii (ATCC 29544, plus four strains isolated from powdered infant formula) was studied, and the sequence compared with those of other Enterobacteriaceae in aspects of genetic variability. Sequence differences between E. sakazakii and other Enterobacteriaceae within the hypervariable regions V1, V2, and V3, respectively, were used to develop two PCR methods for E. sakazakii. PCR1 employed a primer pair located in V1/V2, while PCR2 utilized a primer pair located in V1/V3, respectively. The two PCR methods were tested against a set of 57 E. sakazakii and 148 non-E. sakazakii isolates. PCR1 gave an amplicon with a size of 406 bp and resulted in 100% positive results for E. sakazakii, but also detected Citrobacter koseri/amalonaticus and all nine tested Salmonella enterica serovars. In contrast, PCR2 (amplicon size of 952 bp) gave positive results only for E. sakazakii, thus allowing specific identification of this species. PMID- 17289199 TI - Application of molecular methods for analysing the distribution and diversity of acetic acid bacteria in Chilean vineyards. AB - The presence of acetic acid bacteria populations on grape surfaces from several Chilean valleys is reported. The bacteria were analysed at both the species and the strain level by molecular methods such as RFLP-PCR 16S rRNA gene, RFLP-PCR ITS 16S-23S rRNA gene regions and Arbitrary Primed (AP) PCR. Our results show that there are limited numbers of species of acetic acid bacteria in the grapes and that there is a need for an enrichment medium before plating to recover the individual colonies. In the Northernmost region analysed, the major species recovered was a non-acetic acid bacteria, Stenotrophomonas maltophila. Following the North-South axis of Chilean valleys, the observed distribution of acetic acid bacteria was zonified: Acetobacter cerevisiae was only present in the North and Gluconobacter oxydans in the South. Both species were recovered together in only one location. The influence of the grape cultivar was negligible. Variability in strains was found to be high (more than 40%) for both Acetobacteraceae species. PMID- 17289200 TI - Pathogenesis of Helicobacter pullorum infections in broilers. AB - Four groups of 23 one-day-old broiler chickens were each inoculated by gavage with a different Helicobacter pullorum strain isolated from humans or poultry. As a control, a fifth group of eight animals was inoculated with phosphate-buffered saline. Faecal samples were collected weekly and tested for the presence of H. pullorum DNA using PCR. At 1, 8, 15, 22 and 42 days postinoculation, birds were euthanized and samples from the liver and intestinal tract were histologically, immunohistochemically and bacteriologically examined. The samples were also tested for the presence of H. pullorum DNA by PCR. All animals remained clinically healthy throughout the experiment although mild lesions in the caeca were present in animals inoculated with H. pullorum. In all H. pullorum inoculated groups, DNA of this bacterium was detected in faecal samples until 42 days postinoculation. The main site of colonization was the caecum. Immunohistochemical examination revealed that the bacterium was closely associated with the caecal epithelial cells. It was concluded that H. pullorum may colonize the caecum of broilers and is excreted in their faeces until slaughter age. This implies that chicken meat might constitute a source of infection for human beings. PMID- 17289201 TI - The S-layer proteins of Lactobacillus crispatus strain ZJ001 is responsible for competitive exclusion against Escherichia coli O157:H7 and Salmonella typhimurium. AB - Lactobacillus crispatus ZJ001, isolated from pig intestines and identified by sequencing analysis based on partial 16S rRNA gene, was examined in vitro for probiotic activity exerted by the surface layer proteins (S-layer). The characteristics of L. crispatus ZJ001 were compared to Lactobacillus acidophilus ATCC 4356 from the same genus which also produces the S-layer proteins. The strain ZJ001 was resistant to acidic condition and bile salt. Its antagonistic properties such as adhesion, inhibition of the pathogen growth and competitive exclusion against Escherichia coli O157:H7 and Salmonella typhimurium were apparently advantageous over L. acidophilus ATCC 4356. SDS-PAGE analysis of cell surface proteins revealed the presence of S-layer proteins, approximately at 42 kDa in L. crispatus ZJ001. Removal of the S-layer proteins reduced autoaggregation and adhesion to HeLa cells. The functional role of the S-layer proteins in adhesion was also confirmed by the antibody-mediated inhibition assay using the polyclonal antibody against the S-layer protein. The S-layer proteins from L. crispatus ZJ001 inhibited adhesion of S. typhimurium and E. coli O157:H7 to HeLa cells. These results suggest that L. crispatus ZJ001 possesses probiotic properties and the S-layer proteins are involved in the adhesion and competitive exclusion of pathogens to HeLa cells. PMID- 17289202 TI - Modeling rotavirus-like particles production in a baculovirus expression vector system: Infection kinetics, baculovirus DNA replication, mRNA synthesis and protein production. AB - Rotavirus is the most common cause of severe diarrhoea in children worldwide, responsible for more than half a million deaths in children per year. Rotavirus like particles (Rota VLPs) are excellent vaccine candidates against rotavirus infection, since they are non-infectious, highly immunogenic, amenable to large scale production and safer to produce than those based on attenuated viruses. This work focuses on the analysis and modeling of the major events taking place inside Spodoptera frugiperda (Sf-9) cells infected by recombinant baculovirus that may be critical for the expression of rotavirus viral proteins (VPs). For model validation, experiments were performed adopting either a co-infection strategy, using three monocistronic recombinant baculovirus each one coding for viral proteins VP(2), VP(6) and VP(7), or single-infection strategies using a multigene baculovirus coding for the three proteins of interest. A characteristic viral DNA (vDNA) replication rate of 0.19+/-0.01 h(-1) was obtained irrespective of the monocistronic or multigene vector employed, and synthesis of progeny virus was found to be negligible in comparison to intracellular vDNA concentrations. The timeframe for vDNA, mRNA and VP synthesis tends to decrease with increasing multiplicity of infection (MOI) due to the metabolic burden effect. The protein synthesis rates could be ranked according to the gene size in the multigene experiments but not in the co-infection experiments. The model exhibits acceptable prediction power of the dynamics of intracellular vDNA replication, mRNA synthesis and VP production for the three proteins involved. This model is intended to be the basis for future Rota VLPs process optimisation and also a means to evaluating different baculovirus constructs for Rota VLPs production. PMID- 17289203 TI - Cloning and characterization of penicillin V acylase from Streptomyces mobaraensis. AB - We report on the molecular cloning and characterization of penicillin V acylase (PVA) from an actinomycete, Streptomyces mobaraensis (Sm-PVA), which was originally isolated as an acylase that efficiently hydrolyzes the amide bond of various N-fatty-acyl-l-amino acids and N-fatty-acyl-peptides as well as capsaicin (8-methyl-N-vanillyl-6-nonenamide). In addition, the purified Sm-PVA hydrolyzed penicillin V with the highest activity (k(cat)) among the PVAs so far reported, penicillin G, and 2-nitro-5-phenoxyacetamide benzoic acid. The BLAST search revealed that the Sm-PVA precursor is composed of a polypeptide that is characteristic of enzymes belonging to the beta-lactam acylase family with four distinct segments; a signal sequence (43 amino acids), an alpha subunit (173 amino acids), a linker peptide (28 amino acids), and a beta subunit (570 amino acids). The mature, active Sm-PVA is a heterodimeric protein with alpha and beta subunits, in contrast to PVAs isolated from Bacillus sphaericus and B. subtilis, which have a homotetrameric structure. The amino acid sequence of Sm-PVA showed identities to PVA from S. lavendulae, N-acylhomoserine lactone-degrading acylase from Streptomyces sp., cyclic lipopeptide acylase from Streptomyces sp., and aculeacin A acylase from Actinoplanes utahensis with 68, 67, 67, and 41% identities, respectively. PMID- 17289204 TI - Retroviral integrases that are improved for processing but impaired for joining. AB - Retroviral integrase specifically trims (or processes) the ends of retroviral DNA, then inserts (or joins) these ends into cellular DNA nonspecifically. We previously showed that Rous sarcoma virus integrase with a serine-to-aspartate substitution at amino acid 124 was markedly improved for processing but dramatically impaired for joining, making it the first mutant to separate the activities of integrase in this way. We now show that placing glutamic acid at this residue has the same effect, whereas asparagine or glutamine, which resemble aspartate and glutamate but without the negatively charged acid group, improved processing and impaired joining to a lesser extent. Placing aspartic acid at either of the adjacent residues 123 or 125 also had an intermediate effect. Thus, the charge, structure, and position of the substitution all contribute to the properties of the S124D protein. Infectivity of virions containing these mutations paralleled the in vitro findings, with substitutions having the greatest effect on joining completely blocking replication. Additional studies indicated the replication-defective viruses were blocked at integration and that the S124D protein is impaired at binding nonviral DNA. These functional, biochemical, and genetic data implicate this particular integrase residue as a key part of the binding site for cellular DNA. PMID- 17289205 TI - Efficient gene silencing induction in tomato by a viral satellite DNA vector. AB - Virus-induced gene silencing (VIGS) in tomato (Lycopersicon esculentum Mill.) is currently routinely analysed using Tobacco rattle virus (TRV)-based vector. We recently reported a new vector system modified from DNA beta (DNAm beta) of Tomato yellow leaf curl China virus (TYLCCNV) for VIGS analysis in Solanaceous species including tomato. Here, we describe DNAm beta-induced gene silencing in tomato. We found that DNAm beta-induced gene silencing was initiated from vascular tissues, and later scattered to other tissues. Once initiated in seedlings, the silencing phenotype lasted for the entire life span of the plants, was expressed in a variety of tissues and organs including leaf, shoot, stem, flower and fruit, and could be achieved at any growth stage. It was insensitive to temperature as high as 32 degrees C and no symptoms were observed in silenced plants. The DNAm beta vector worked efficiently in at least seven tomato cultivars, indicating that this system has great potential as a versatile VIGS system for routine functional analysis of genes in tomato. PMID- 17289206 TI - Controlled-release of epidermal growth factor from cationized gelatin hydrogel enhances corneal epithelial wound healing. AB - We designed a new ophthalmic drug-delivery system for epidermal growth factor (EGF) from the biodegradable hydrogel of cationized gelatin. We placed a cationized gelatin hydrogel (CGH) with incorporated (125)I-labelled EGF in the conjunctival sac of mice and measured the residual radioactivity at different times to evaluate the in vivo profile of EGF release. Approximately 60-67% and 10 12% of EGF applied initially remained 1 and 7 days after application, respectively; whereas EGF delivered in topically applied solution or via EGF impregnation of soft contact lenses disappeared within the first day. We also placed CGH films with 5.0 mug of incorporated EGF on round corneal defects in rabbits to evaluate the healing process using image analysis software and to assess epithelial proliferation immunohistochemically by counting the number of Ki67-positive cells. The application of a CGH film with incorporated EGF resulted in a reduction in the epithelial defect in rabbit corneas accompanied by significantly enhanced epithelial proliferation compared with the reduction seen after the topical application of EGF solution or the placement of an EGF-free CGH film. The controlled release of EGF from a CGH placed over a corneal epithelial defect accelerated ocular surface wound healing. PMID- 17289207 TI - Delivery of ethinylestradiol from film forming polymeric solutions across human epidermis in vitro and in vivo in pigs. AB - Film forming polymeric solutions may present an alternative to the common transdermal dosage forms such as patches or gels. To evaluate the potential of these systems for transdermal drug delivery the permeation of ethinylestradiol from four formulations with different polymers was tested across heat separated human epidermis. The formulation with the best results was then modified by incorporating chemical enhancers to further increase the efficiency of the delivery system. Finally, drug delivery from the developed film forming systems was compared to a commercially available transdermal patch in vitro as well as in vivo in pigs. Among the tested preparations the formulation with polyurethane-14 AMP-acrylates copolymer (DynamX) showed the highest ethinylestradiol permeation. The drug transport was further increased with the incorporation of oleic acid as penetration enhancer, especially when used in combination with propylene glycol. The enhancing effect of oleic acid/propylene glycol was concentration-dependent and increased disproportionately with rising enhancer content. The film forming solution showed a higher ethinylestradiol permeation through heat separated human epidermis than the commercial EVRA patch in vitro and achieved measurable plasma concentrations of ethinylestradiol in vivo in pigs. These promising results encourage the further development of film forming polymeric solutions as novel transdermal dosage form. PMID- 17289209 TI - Reconstruction of health service systems in the post-conflict Northern Province in Sri Lanka. AB - Public health problems in armed conflicts have been well documented, however, effective national health policies and international assistance strategies in transition periods from conflict to peace have not been well established. After the long lasted conflicts in Sri Lanka, the Government and the rebel LTTE signed a cease-fire agreement in February 2002. As the peace negotiation has been disrupted since April 2003, a long-term prospect for peace is yet uncertain at present. The objective of this research is to detect unmet needs in health services in Northern Province in Sri Lanka, and to recommend fair and effective health strategies for post-conflict reconstruction. First, we compared a 20-year trend of health services and health status between the post-conflict Northern Province and other areas not directly affected by conflict in Sri Lanka by analyzing data published by Sri Lankan government and other agencies. Then, we conducted open-ended self-administered questionnaires to health care providers and inhabitants in Northern Province, and key informant interviews in Northern Province and other areas. The major health problems in Northern Province were high maternal mortality, significant shortage of human resources for health (HRH), and inadequate water and sanitation systems. Poor access to health facilities, lack of basic health knowledge, insufficient health awareness programs for inhabitants, and mental health problems among communities were pointed by the questionnaire respondents. Shortage of HRH and people's negligence for health were perceived as the major obstacles to improving the current health situation in Northern Province. The key informant interviews revealed that Sri Lankan HRH outside Northern Province had only limited information about the health issues in Northern Province. It is required to develop and allocate HRH strategically for the effective reconstruction of health service systems in Northern Province. The empowerment of inhabitants and communities through health awareness programs and the development of a systematic mental health strategy at the state level are also important. It is necessary to provide with the objective information of gaps in health indicators by region for promoting mutual understanding between Tamil and Sinhalese. International assistance should be provided not only for the post-conflict area but also for other underprivileged areas to avoid unnecessary grievance. PMID- 17289208 TI - A type of esophageal stent coating composed of one 5-fluorouracil-containing EVA layer and one drug-free protective layer: in vitro release, permeation and mechanical properties. AB - A type of esophageal stent coating was investigated, which consists of one 5 fluorouracil (5-FU)-containing ethylene-vinyl acetate (EVA) copolymer layer and one drug-free EVA protective layer. The amount of 5-FU permeated through the protective layer (100 mum) is thousands of times lower than that of 5-FU released from the drug-loaded layer, indicating that the coating releases drug molecules in a unidirectional fashion. The barrier of the protective layer can be attributed to a tiny flux of 5-FU through the EVA film. In vitro release profiles of the stent coatings with various drug contents were investigated in pH 6.5 phosphate buffer solution. The results show that, the burst effect is not obvious for the coatings with 20-50% of 5-FU and the release profiles can be characterized by a first faster release rate phase followed by a decrease in release rate. The release data in the early and late stages can all be well fitted with zero-order kinetics, and the possible reasons for the release profiles were discussed. The rate of 5-FU permeation through porcine esophageal mucosa from the coatings can be adjusted by changing drug content of the coatings. The increase of drug content of the coatings significantly leads to the decrease of the maximum elongation, maximum tensible strength and maximum tear strength, and the increase of the modulus of elasticity. The coatings with 20-60% of drug attached to a stent can endure repeated binding and liberation via a stent introducer. PMID- 17289210 TI - The MESH approach: strengthening public health systems for the MDGs. AB - This article addresses some of the complexities in the interactions both within the public health system and between that and civil society. It examines what needs to be done to improve the capacity of health systems, primarily through building relevant infrastructure (what is called MESH--management, economic, social and human - infrastructure) where this is lacking. This lack is most likely to occur in poorer communities and health districts. The problem of absorption and appropriate use of funds in disadvantaged areas has been highlighted as a critical bottleneck to the achievement of the millennium development goals (MDGs). MESH is defined as infrastructure which is built to improve the capacity of communities and other entities to implement health service programs efficiently. We employ this concept to determine how best to invest in health in poor areas so that they can better use any additional resources they receive. The article reviews some initial explorations of the relevance of MESH building strategies in South Africa. The research shows the usefulness of the MESH approach which requires inter alia a more developmental approach that goes beyond the vertical silos of much influential prioritization literature over the last two decades. In practice it is clear that MESH will vary from location to location which reflects the fact that investing in successful health strategies must take into account the voices of the local people with respect to what they want from their health services. PMID- 17289211 TI - Combining eigenvector methods and support vector machines for detecting variability of Doppler ultrasound signals. AB - In this paper, the multiclass support vector machines (SVMs) with the error correcting output codes (ECOC) were presented for detecting variabilities of the multiclass Doppler ultrasound signals. The ophthalmic arterial (OA) Doppler signals were recorded from healthy subjects, subjects suffering from OA stenosis, subjects suffering from ocular Behcet disease. The internal carotid arterial (ICA) Doppler signals were recorded from healthy subjects, subjects suffering from ICA stenosis, subjects suffering from ICA occlusion. Methods of combining multiple classifiers with diverse features are viewed as a general problem in various application areas of pattern recognition. Because of the importance of making the right decision, better classification procedures for Doppler ultrasound signals are searched. Decision making was performed in two stages: feature extraction by eigenvector methods and classification using the SVMs trained on the extracted features. The research demonstrated that the multiclass SVMs trained on extracted features achieved high accuracy rates. PMID- 17289212 TI - Multidimensional validation of a numerical model for simulating a DNAPL release in heterogeneous porous media. AB - A fixed-volume release of 1,2-DCE, tracked in space and time with a light transmission/image analysis system, provided a data set for the infiltration, redistribution, and immobilisation of a dense non-aqueous phase liquid (DNAPL) in a heterogeneous porous medium. The two-dimensional bench scale flow cell was packed with a spatially correlated, random heterogeneous distribution of six sand types. In order to provide the necessary modelling parameters, detailed constitutive relationships were measured at the local scale for the six sands. These experiments revealed that nonwetting phase (NWP) relative permeability saturation (k(rN)-S(W)) relationships are strongly correlated to sand type. Trends in the best-fit k(rN)-S(W) parameters reflected a positive correlation between mean grain diameter and the maximum NWP relative permeability, k(rN)(max). Multiphase flow simulations of the bench scale experiment best reproduced the experimental observations, producing excellent matches in both time and space, when the measured, correlated local scale k(rN)-S(W) relationships were employed. PMID- 17289213 TI - Gadolinium is quantifiable within the tissue of patients with nephrogenic systemic fibrosis. PMID- 17289214 TI - New prognostic relevant factors in primary cutaneous diffuse large B-cell lymphomas. AB - BACKGROUND: There is a growing body of literature that has enhanced our understanding of the biology of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) including in the context of gene profiling studies. Recent studies have demonstrated an activated proliferation profile associated with leg type lymphoma including overexpression of proto-oncogenes PIM1, PIM2, and cMYC, and the transcription factors MUM1 and OCT2. Although gene profiling is very useful in understanding the molecular basis of diffuse large B-cell lymphoma (LBCL), it is not practical from a routine diagnostic perspective. In this regard, the purpose of the study was to further define an armamentarium of easily applied immunohistochemical stains to accurately prognosticate PCDLBCL. METHODS: In all, 35 patients with PCDLBCL, 14 of follicle center and 21 of leg type, were analyzed using antibodies against CD5, CD138, BCL2, BCL6, OCT2, MUM1, FOXP1, and cMYC. Findings were correlated with clinical data. RESULTS: All cases stained negative for CD5 and CD138. Both subtypes differed in distinct staining patterns for BCL6, BCL2, OCT2, MUM1, and FOXP1. Staining for BCL2, OCT2, and/or MUM1 was associated with poor, and BCL6 with a favorable prognosis. Expression of cMYC was irrespective of prognosis or subtype, whereas ulceration or primary manifestation on the leg or multiple lesions was indicative for worse prognosis. LIMITATIONS: Case number was a limitation. CONCLUSION: Discriminating PCDLBCL supports the validity of the World Health Organization/European Organization for Research and Treatment of Cancer classification. To identify risk factors in patients with PCDLBCL we recommend thorough evaluation of clinical presentation and exploratory staining pattern for BCL2, BCL6, MUM1 and OCT2. PMID- 17289215 TI - Impact and cost of infection control measures to reduce nosocomial transmission of extended-spectrum beta-lactamase-producing organisms in a non-outbreak setting. AB - We evaluated the impact of infection control interventions to reduce nosocomial extended-spectrum beta-lactamase (ESBL) transmission in a non-outbreak setting. This study was conducted at a tertiary 1200-bed hospital in Canada. The incidence of ESBLs was based on recovery of clinical isolates and assessed prospectively from 1999 to 2005. The incidence increased significantly from 0.28 to 0.67 per 1000 admissions during this period (P<0.001), reflecting an increase in the regional ESBL incidence from 1.32 to 9.28 per 100 000 population (P<0.001). Despite this increase, nosocomial ESBL rates increased only marginally, suggesting that infection control measures had an impact on nosocomial transmission. Infection control measures consisted of isolating all ESBL patients, as well as implementing the use of contact precautions for those with a high risk for transmission. The cost of these measures was CN$138 046.00 per year and CN$3191.83 per case admitted. A combination of control measures including active surveillance cultures, contact precautions for all colonized or infected patients and antimicrobial stewardship is required to significantly reduce the incidence of ESBLs. PMID- 17289216 TI - Structure-activity study on the LH- and FSH-releasing and anticancer effects of gonadotropin-releasing hormone (GnRH)-III analogs. AB - GnRH-III was reported to have selective FSH-releasing activity in rats and significant anticancer potency on human breast cancer cells. To improve either of these effects, 14 analogs were synthesized and investigated for FSH/LH stimulation and breast cancer inhibition. Analogs with single amino acid changes in positions 5-7 or 10 showed small or no difference in the FSH- or LH-releasing activity compared with GnRH-III but their anticancer potency decreased significantly. Modification of the terminal amino acids, side chain cyclization at the 6-8 regions, or combined amino acid changes at positions 4, 6 and/or 8 resulted in the decrease of both effects. Gonadotropin-releasing activity of Arg(8)-GnRH-III was improved 3-11-fold. A copolymer conjugate of GnRH-III showed 2-3-fold anticancer activity while losing endocrine potency. CONCLUSION: The activation of GnRH-receptors on pituitary and breast cancer cells requires a specific structure and/or conformation that makes possible to improve the anticancer selectivity of GnRH analogs. PMID- 17289217 TI - Thymosin beta4 and thymosin beta4-derived peptides induce mast cell exocytosis. AB - The peptide thymosin beta4 (Tbeta4) promotes angiogenesis and wound healing. Mast cells are involved in these processes as well and therefore we investigated the effect of Tbeta4 on mast cells. Exposure to 0.2-2000nM Tbeta4 induced mediator release (up to 23%) in murine peritoneal and human HMC-1 mast cells in a concentration-dependent manner. While the peptide AcSDKP, matching the 4 N terminal amino acid residues of Tbeta4, mediated low but detectable mediator release, peptides corresponding to the Tbeta4 amino acid sequences 16-38 and 17 23 stimulated mast cells mediator release on a level equal to or higher than that observed with native Tbeta4. These observations and certain characteristics of Tbeta4-mediated mast cell activation suggest that the actin-binding motif LKKTET present in Tbeta4 (amino acid 17-22) might be implicated in this process. Thus, Tbeta4 activates mediator release in mast cells by a process that possibly involves an actin-binding motif and this could be important for understanding the mechanisms of Tbeta4-mediated effects in vivo. PMID- 17289218 TI - The identification of surface proteins of Burkholderia pseudomallei. AB - Burkholderia pseudomallei, the causative agent of the disease melioidosis is a human pathogen endemic in Northern Australia and South-East Asia. At present there is no available vaccine or effective treatment for this disease. Surface proteins play crucial roles in the host-pathogen interaction and have been exploited as vaccine candidates and diagnostic targets. Therefore, we wished to identify immunogenic surface proteins of B. pseudomallei. To this end we used two proteomic-based approaches in parallel: a biotinylation approach for the detection of surface located proteins identified 35 proteins, while screening with human sera identified 12 immunogenic proteins. Nine of these proteins were identified by both methods indicating that they may be both surface located and immunogenic: these proteins will be evaluated further as vaccine candidates and diagnostic targets. PMID- 17289219 TI - Formaldehyde treatment increases the immunogenicity and decreases the toxicity of Haemophilus ducreyi cytolethal distending toxin. AB - Haemophilus ducreyi cytolethal distending toxin (HdCDT) is a tripartite AB toxin, which causes DNA damage in affected cells. We investigated the effects of formaldehyde on the chemical, biological, and immunological properties of the HdCDT complex, which was purified by immobilizing the glutathione S-transferase (GST)-CdtB fusion protein, followed by binding of the CdtA and CdtC recombinant proteins. The HdCDT was treated with increasing concentrations of formaldehyde in the presence of lysine. The treatment of HdCDT at 1 and 0.1 mg protein/ml with 320 and 80 mM of formaldehyde, respectively, resulted in the complete abrogation of cytotoxic activity, loss of DNase activity, and loss of binding capacity to HeLa cells. The toxoid showed protein bands of 75-150 kDa in SDS-PAGE, composed of the three cross-linked CDT components detected by immunoblotting. Three doses of 10 microg protein/mouse of the formaldehyde-treated HdCDT elicited toxin neutralizing antibodies at titers about 200 times higher than those elicited by the native toxin. The described methodology may be applied to produce immunogenic toxoids from other CDTs, which might be used as candidate components in vaccines against CDT-producing bacteria, including H. ducreyi. PMID- 17289220 TI - Developing an HPV vaccine to prevent cervical cancer and genital warts. AB - The challenges of the journey from target identification through development of a prophylactic quadrivalent human papillomavirus (HPV) vaccine have been met in Gardasil. Cervical cancer is the second leading cause of cancer-related death in women worldwide. Approximately 70% of cervical cancer is caused by infection with HPV types 16 and 18 and approximately 90% of genital warts are caused by HPV types 6 and 11. The quadrivalent HPV vaccine was generated by expression of the major capsid protein (L1) of HPV types 16, 18, 6 and 11 in yeast. L1 proteins self assemble into pentamer structures and these pentamer structures come together to form virus-like particles (VLPs). The VLPs are antigenically indistinguishable from HPV virions. The VLPs contain no viral DNA and therefore the vaccine is non-infectious. Gardasil is composed of VLPs of HPV types 16, 18, 6 and 11 conjugated to a proprietary amorphous aluminum hydroxyphosphate sulfate adjuvant. The results of a rigorous clinical program have demonstrated that the vaccine is safe and highly efficacious in preventing dysplasias, cervical intraepithelial neoplasias (CIN 1-3) the precursors of cervical cancer and external genital lesions caused by vaccine-HPV types. In conclusion, Gardasil addresses a major medical need, that is, reduction of HPV-related disease including cervical cancer as a safe, immunogenic, and highly efficacious vaccine. PMID- 17289221 TI - Immunization with the heptavalent pneumococcal conjugate vaccine in Bangladeshi infants and effects of zinc supplementation. AB - BACKGROUND: Zinc deficiency is known to impair immunologic functions. However, the effect of zinc supplementation on immune response to polysaccharide vaccines is not known. OBJECTIVE: To determine the immunogenicity of the heptavalent Pneumococcal protein conjugate (PNC) vaccine in poor Bangladeshi infants and to assess the effect of zinc supplementation on immune response to the PNC vaccine. DESIGN: We immunized a sub-cohort of 241 infants who had previously received three doses of a Hib conjugate vaccine with three doses of the heptavalent PNC vaccine at 4 weeks intervals beginning at 18+/-1 weeks of age. The infants were supplemented with daily 5 mg zinc or placebo from 4 to 33 weeks of age. Response to each of the seven PNC serotypes were assessed at 4, 24 and 33 weeks of age. RESULTS: After three doses of PNC, at 29 weeks of age, geometric mean titres for the pneumococcal serotypes ranged from 3.68 to 13.34 microg/ml. Titres were significantly higher for infants who had received PNC compared to infants who had only received DTP-Hib. Zinc supplementation resulted in higher titres for serotype 9V (4.09 microg/ml; [95% CI: 3.27; 5.10] and 3.33 microg/ml; [95% CI: 2.79; 3.96] for zinc and placebo group, respectively; p<0.05) after three doses but had no effect on other serotypes. CONCLUSIONS: A heptavalent PNC vaccine proved to be safe and immunogenic in Bangladeshi infants. Zinc supplementation enhanced the immune response to only one of the serotypes (9V). However, there was no effect on other serotypes. PMID- 17289222 TI - GTU-MultiHIV DNA vaccine results in protection in a novel P815 tumor challenge model. AB - A novel animal model for testing the immunogenicity and protective immune response induced by HIV-1 DNA vaccines was developed. DBA/2 mice were immunized with GTU-MultiHIV DNA encoding multigene for Rev, Nef, Tat, optp17/24 and a stretch of Pol/Env epitopes. A single GTU-MultiHIV B-clade specific plasmid or Auxo-GTU-MultiHIV(mix) (mixture of four plasmids with A, B, C and FGH clade specific MultiHIV antigens) were administered via gene gun and cell-mediated and humoral immune responses were analysed. The protective efficacy of the immune response was evaluated by challenging the mice with syngeneic tumor cells (P815) stably transfected with the MultiHIV fusion gene. Our results show that the strong MultiHIV-specific immune response generated by the GTU-MultiHIV vaccines in DBA/2 mice was able to delay the tumor growth substantially, indicating that the CTL response detected in vitro confers protection in vivo. The model described here is a safe and feasible in vivo assay for assessment of the vaccine potency to induce protective cell-mediated immune responses. PMID- 17289224 TI - Enteral vaccination of rats against Fasciola hepatica using recombinant cysteine proteinase (cathepsin L1). AB - Cysteine proteinases released by Fasciola hepatica play a key role in parasite feeding, migration through host tissues and in immune evasion. Hence, a recombinant cysteine proteinase (CPFhW) expressed as inclusion bodies in Escherichia coli was used for enteral vaccination of rats against fasciolosis. We managed to activate this proteinase and found it to have cathepsin L1-like substrate preference. Enteral vaccination of rats induced a 78-80% protection against challenge with fluke metacercariae (mc). The immunised rats showed clear immunological response. The challenge with mc caused a remarkable infiltration of eosinophils into the peritoneal cavity of both the vaccinated rats and challenge control rats. However, CD8+ and CD4+ lymphocytes appeared in significantly higher numbers in the peritoneal fluid of vaccinated rats than in controls. PMID- 17289223 TI - Immunogenicity and safety of a strain-specific MenB OMV vaccine delivered to under 5-year olds in New Zealand. AB - To control the devastating group B meningococcal epidemic in New Zealand a strain specific OMV vaccine (MeNZB) was extensively tested before vaccination of >1,000,000 people under 20 years. After the three-dose course 75% of 6-8-month old infants and 16-24-month-old toddlers showed four-fold increases in bactericidal antibodies. In 6-10-week-old infants a fourth dose was needed to obtain similar results. After primary vaccination, the antibody titre decline was most pronounced among the youngest but both young infants and toddlers showed a clear booster response to a fourth dose. MeNZB was safe and well tolerated. The comprehensive post-licensure safety surveillance revealed no safety concerns. PMID- 17289225 TI - Development of vaccines and passive immunotherapy against SARS corona virus using SCID-PBL/hu mouse models. AB - We have investigated novel vaccine strategies against severe acute respiratory syndrome (SARS) CoV using cDNA constructs encoding the structural antigens: (S), (M), (E), or (N) protein, derived from SARS CoV. PBL from healthy human volunteers were administered i.p. into IL-2 receptor gamma-chain disrupted SCID mice, and SCID-PBL/hu mice were constructed. These mice can be used to analyze the human immune response in vivo. SARS M DNA vaccine and N DNA vaccine induced human CTL specific for SARS CoV antigens. Alternatively, SARS M DNA vaccines inducing human neutralizing antibodies and human monoclonal antibodies against SARS CoV are now being developed. These results show that these vaccines can induce virus-specific immune responses and should provide a useful tool for development of protective and therapeutic vaccines. PMID- 17289226 TI - Humanization and mammalian expression of a murine monoclonal antibody against Venezuelan equine encephalitis virus. AB - The murine monoclonal antibody 1A4A1 can strongly neutralize Venezuelan equine encephalitis virus and is a good candidate for development of humanized antibody. Humanization of 1A4A1 variable domains was achieved by grafting 1A4A1 complementarity-determining regions (CDRs) onto the frameworks of human immunoglobulin germline variable and joining gene segments, whose CDRs have the highest similarities to 1A4A1 ones. The humanized 1A4A1 variable domains were further grafted onto human heavy and light chain constant domains to assemble the whole antibody gene, which was then synthesized and cloned to an adenoviral vector. After expression in HEK 293 cells and purification by protein L column, the humanized antibody was demonstrated to retain antigen-binding specificity and neutralizing activity. PMID- 17289227 TI - Avian and pandemic influenza: an overview. AB - Influenza A/H5N1 (avian influenza) has now caused 258 human infections (as of November 13, 2006), with an approximate 50% mortality rate. Because the virus is novel in terms of antigenic type and causes infection and illness, and because humans have no pre-existing immunity, the conditions for a possible pandemic exist. Additionally, wild migratory birds appear to be spreading the virus across ever larger geographic areas, and newer clade 2 influenza A/H5N1 viruses have begun to emerge. The US Congressional Budget Office has formally modeled the likely consequences of pandemic influenza and estimates that up to 2 million of the US population might die, with up to 40% of all workers ill for as long as 3 or more weeks. This brief overview will review basic virologic, immunologic and epidemiologic information relevant to understanding and preparing for this threat. In particular, the role of avian influenza vaccines will be reviewed. PMID- 17289228 TI - Transfer of chlorine from the environment to agricultural foodstuffs. AB - The factors governing chlorine transfer from Phaeozem and Greyzem soils to various important crop species (foodstuff and forage) were determined in natural conditions in the Kiev region of Ukraine. The stable chlorine concentration ratio (CR) values were the lowest in apple (0.5+/-0.3) and strawberry (2+/-1), higher in vegetables (5+/-3), seeds (15+/-7) and reached a maximum in straw (187+/-90). The average CR values of 36Cl were estimated for the most important crops using all experimental data on 36Cl and stable chlorine transfer into plants from various soils. It was experimentally shown that boiling potatoes in water leads to an equilibrium between 36Cl specific content in the water and moisture in the cooked potato. The 36Cl processing factor (PF) for boiling various foodstuffs is equal to the ratio of water mass in the cooked foodstuff to the total water mass (in the food and the decoction). 36Cl PF for cereal flour can be estimated as 1. The 36Cl processing factor for dairy products is equal to the ratio of residual water mass in the product to initial water mass in milk. At a 36Cl specific activity in soil of 1 Bq kg-1, the estimated annual dietary 36Cl intake into human organism (adult man) is about 10 kBq. Sixty to seventy percent of the above amount will be taken in via milk and dairy products, 7-16% via meat, 14-16% via bread and bakery items and 8-12% via vegetables. The highest annual 36Cl intake, 10.7 kBq, is predicted for 1-year-old children. The expected effective doses from annual 36Cl intake are higher for younger age groups, increasing from 0.008 mSv in adults to 0.12 mSv in 1-year-old children. PMID- 17289229 TI - Optimisation of systems to locate discrete gamma-ray sources within a large search area. AB - Most systems used to locate discrete gamma-ray sources involve systematically passing a detector over the search area while seeking a significant increase in the observed count-rate. This paper discusses the ways in which such systems may be designed to maximise the probability of locating a source. It is shown that optimised systems use a collimated, energy-discriminating detector and overlapping counting intervals determined by the scanning geometry and speed. PMID- 17289230 TI - 'Collateral damage': the impact of war on the health of women and children in Iraq. PMID- 17289231 TI - Cryoglobulinemia. AB - Cryoglobulinemia refers to the presence in serum of immunoglobulins that precipitate at a cold temperature. Type I cryoglobulins are single monoclonal immunoglobulins usually associated with haematological disorders. Types II and III are mixed cryoglobulins, composed of monoclonal or polyclonal IgM respectively, having rheumatoid factor activity that bind to polyclonal immunoglobulins. Mixed cryoglobulinemia (MC) syndrome is a consequence of immune complex mediated vasculitis and is characterized by a typical clinical triad: purpura, weakness, arthralgias; many organs particularly kidney and peripheral nervous system may be involved. MC may be associated with infectious and systemic disorders and since 1990 studies have demonstrated that hepatitis C virus (HCV) may be considered the principal trigger of the disease. The relation between MC and HCV infection shows new insights in the interpretation of the link between viral infection, autoimmune phenomena and lymphoproliferative disorders evolution. In fact, the virus chronically stimulates B-cell polyclonal proliferation from which a monoclonal population may emerge. In symptomatic patients with HCV related MC therapeutic strategy should include an attempt at viral eradication. Antiviral therapy may also be effective in determining the regression of B-cell lymphoproliferative disorder. Rituximab could represent a safe and effective alternative to standard immunosuppression and exerts selective B-cell control. PMID- 17289232 TI - Fate of metal-associated POM in a soil under arable land use contaminated by metallurgical fallout in northern France. AB - Organic matter is a major metal-retaining constituent in soils. Among the diversity of organic components in soils, particulate organic matter (POM) accumulates large amounts of metals, but the fate of such metal-associated POM is unknown. We studied different POM size fractions and their corresponding mineral size-fractions isolated from the surface horizon of a soil affected by metallurgical fallout. Analyses of total and EDTA extractible metal contents performed on all size fractions demonstrated that with decreasing POM size, larger metal concentrations were observed but they were less extractable. Micromorphological study revealed the occurrence of opaque parts in decaying POM fragments and their individualization as fine, irregularly shaped opaque fragments in the soil matrix. This work suggested a mutual sequestration of metal pollutants and organic carbon as micro-meter sized, metal-enriched organic particles derived from POM, representing an original pathway for natural attenuation of risk related to metal contaminated soils. PMID- 17289234 TI - Effect of organic suspended solids and their sedimentation on the surrounding sea area. AB - A study of sediment contamination was made in one of the 23 specific designated important ports in Japan, the inner part of which had been used as wood pool. The study focused on the relationship between contaminants and organic matter in terms of ignition loss and the impact of the wood pool on the port area. Organic matter exists in the form of suspended solids and deposits. Sediment samples were taken from the mouths of the rivers feeding into Shimizu Port, from the wood pool and from Shimizu Port. Samples within Shimizu Port showed that as the ignition loss decreased with distance from the wood pool, other properties including the concentrations of trace metals, ignition loss and sulfide content also decreased with the distance. In conclusion, Shimizu Port seems to function as a buffer area between the wood pool and Suruga Bay. PMID- 17289233 TI - Biomonitoring in a clean and a multi-contaminated estuary based on biomarkers and chemical analyses in the endobenthic worm Nereis diversicolor. AB - Relationships between biochemical and physiological biomarkers (acetylcholinesterase [AChE], catalase, and glutathione S-transferase [GST] activities, thiobarbituric acid reactive substances, glycogen, lipids and proteins) and accumulated concentrations of contaminants (polychlorinated biphenyls [PCBs], polycyclic aromatic hydrocarbons and metals) were examined in the keystone species Nereis diversicolor. The chemical analyses of worms and sediments allowed the designation of the Seine estuary and the Authie estuary as a polluted and relatively clean site respectively. Worms from the Seine estuary exhibited higher GST and lower AChE activities. Generally, larger worms had higher concentrations of energy reserves. Principal component analyses clearly highlighted intersite differences: in the first plan, GST activities and chemical concentrations were inversely related to concentrations of energy reserves; in the second one, PCB concentrations and AChE activity were inversely related. Depleted levels of energy reserves could be a consequence of combating toxicants and might predict effects at higher levels of biological organization. The use of GST and AChE activities and energy reserve concentrations as biomarkers is validated in the field in this keystone species. PMID- 17289235 TI - Towards a theory of tiered testing. AB - Tiered testing is an essential part of any resource-efficient strategy for the toxicity testing of a large number of chemicals, which is required for instance in the risk management of general (industrial) chemicals, In spite of this, no general theory seems to be available for the combination of single tests into efficient tiered testing systems. A first outline of such a theory is developed. It is argued that chemical, toxicological, and decision-theoretical knowledge should be combined in the construction of such a theory. A decision-theoretical approach for the optimization of test systems is introduced. It is based on expected utility maximization with simplified assumptions covering factual and value-related information that is usually missing in the development of test systems. PMID- 17289236 TI - Clinical and social determinants of psychotropic drug prescription for schizophrenia outpatients in China. AB - To date, few studies have investigated prescription patterns of psychotropic drugs in Chinese patients with schizophrenia in general and outpatients in particular. This study examined the role that socio-demographic and clinical factors play in determining psychotropic drug prescriptions for schizophrenia outpatients in China. Two hundred and fifty-five and 250 clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong (HK) and Beijing (BJ) respectively, using standardized assessment instruments. Prescriptions of psychotropic drugs for all 505 subjects were collected at the time of the assessment. The relationship between antipsychotic drug prescription patterns and a host of socio-demographic and clinical variables was analyzed and compared between the two study sites. Prescription patterns were quite different for the two ethnically homogenous and clinically very similar samples. In multiple logistic regression analyses, the use of depot antipsychotics (DA) and site (HK vs BJ) both significantly predicted antipsychotic polypharmacy (APP), while symptoms of anxiety, use of clozapine and APP and site predicted use of DA. Age, number of hospitalizations, site, and use of DA predicted use of clozapine. No significant differences were found between the quality of life domains of patients with respect to APP, DA, and clozapine. A complex web of economic and clinical factors and health policies plays an important role in determining psychotropic drug prescription practices for Chinese outpatients with schizophrenia. PMID- 17289237 TI - Quality of life and subjective well-being during treatment with antipsychotics in out-patients with schizophrenia. AB - OBJECTIVE: To assess the Quality of Life (QOL) in outpatients with schizophrenia under antipsychotics from two perspectives: a "subjective" perspective as rated by the patient and an "objective" perspective as rated by the physician. METHOD: EASE (External Assessment of Quality of Life in Out-patients with Schizophrenia) is a 12-month, prospective, naturalistic study of the QOL in patients on antipsychotic treatment for schizophrenia in an out-patient setting in Germany. The study included 1462 patients who were initiated on a new antipsychotic or switched to another antipsychotic. The Subjective Well-being under Neuroleptics scale (SWN) and the Quality of Life Scale (QLS) were used to assess the QOL in these patients. The Clinical Global Impression (CGI) scale was used to assess overall symptom severity. Four cohorts were identified and evaluated: (a) patients treated with olanzapine monotherapy (N=1007), (b) another atypical antipsychotic as monotherapy (N=335), (c) a typical antipsychotic as monotherapy (N=32) and (d) combination therapy with more than one antipsychotic (N=88). RESULTS: QOL as assessed by both SWN and QLS improved in all treatment cohorts. SWN responses in the respective cohorts were (a) 52.3%, (b) 38.8%, (c) 31.3% and (d) 44.3%, whilst the QLS responses were (a) 58.2%, (b) 45.1%, (c) 59.4% and (c) 40.9%. Symptom severity as assessed by the CGI also improved over time regardless of the type of antipsychotic. An increase of one point on the CGI corresponded to a change in SWN total score of -9.67 points and a change in QLS total score of 13.36 points. CONCLUSIONS: Both QOL and symptom severity improved over the 12 month study period, regardless of the type of antipsychotic taken. QOL improvement as perceived both from a "subjective" and an "objective" perspective was greatest in the cohort on olanzapine monotherapy. PMID- 17289238 TI - Aripiprazole in delusional parasitosis: Case report. PMID- 17289239 TI - Striatal and nigral COX-2 expression after chronic typical and atypical neuroleptic administration in rats. AB - Haloperidol, but not clozapine, induces dopaminergic nigrostriatal degeneration. However, the mechanisms by which haloperidol causes neurotoxicity are not fully understood. An increase in cyclooxygenase-2 (COX-2) expression has been observed correlated with nigrostriatal degeneration. We investigated the modifications of striatal and nigral COX-2 expression induced by chronic haloperidol and clozapine administration. Rats were treated for 21 days with: haloperidol (1 mg/kg), clozapine (1 mg/kg) or saline. No significant differences were observed in striatal and nigral COX-2 expression between haloperidol and clozapine-treated animals. This observation might suggest that nigral COX-2 expression is not the underlying mechanisms involved in haloperidol-induced dopaminergic neurodegeneration. PMID- 17289240 TI - Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer's disease. AB - Neuropsychological deficits, such as poor episodic memory, are consistent features of mild cognitive impairment and also that of early stage of dementia. The aim of the present study was to detect cognitive dysfunction among patients with Alzheimer's disease or with mild cognitive impairment (MCI), which refers to a transitional state between the cognition of normal aeging and mild dementia regarded as a high-risk condition for the development of clinically probable Alzheimer's disease (AD). Computerized tests of memory, attention and executive functions were studied in groups of AD subjects (n=15) and MCI subjects (n=25). On all measures, the performance of the AD group was significantly weaker compared to healthy individuals or to the MCI group. The performance of both the AD and MCI patients in the Paired Associate Learning test was significantly impaired, which may suggest that MCI patients are already in the early stages of the disease. PMID- 17289241 TI - Fertility and early embryonic development toxicity of penequine hydrochloride in mice. AB - Penequine hydrochloride, a novel anticholinergic agent, was developed as an effective treatment for organophosphorus intoxication. The potential for penequine hydrochloride to induce fertility and early embryonic developmental toxicity was evaluated in AMMS-1 mice. Totally 320 healthy, sexual mature and nulliparous AMMS-1 mice were orally treated with the chemical in drinking water at dose levels of 0, 2.5, 12.5 and 62.5 mg/L from 60 days before cohabitation to successful copulation in 160 males and from two weeks before cohabitation to GD 6 in 160 females, respectively. All the parental mice were observed for body weights, water consumption and any abnormal change during treatment period. Caesarean sections were carried out on day 14 of pregnancy in half assumed pregnant females, and all the intrauterine data were recorded. Pups naturally delivered by the other half females were weighed, and examined for viability, sex ratio and gross malformations. About 7 days after cohabitation period, all the paternal males were examined for epididymal and testicular weights, sperm number and sperm motility. The decreases in fertility/fecundity indices and maternal weight gain were found at high-dose level in both caesarean sections and natural delivery observations. The primary developmental toxicity of the chemical included decreases in relative organ (epididymis, liver and lung) weights at mid- and high-dose levels in pups on postnatal day (PND) 35. The cause of both the decreased fertility/fecundity indices in F0 males and the decreased relative organ weights in F1 pups are not well known but are presently under investigation. Under the experimental conditions, penequine hydrochloride did not produce any adverse effects (expect the decreases in certain relative organ weights) up to and including 12.5 mg/L (2.53 mg/kg/day in males and 2.19 mg/kg/day in females) corresponding to approximately 72 times above anticipated dosage in human. PMID- 17289242 TI - Preventive effect of naringin on isoproterenol-induced cardiotoxicity in Wistar rats: an in vivo and in vitro study. AB - This study was aimed to evaluate the preventive role of naringin on heart weight, blood glucose, total proteins, albumin/globulin (A/G) ratio, serum uric acid, serum iron, plasma iron binding capacity and membrane bound enzymes such as sodium potassium-dependent adenosine triphosphatase (Na(+)/K(+) ATPase), calcium dependent adenosine triphosphatase (Ca(2+) ATPase) and magnesium-dependent adenosine triphosphatase (Mg(2+) ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats and in vitro free radical scavenging assay. Male albino Wistar rats were pretreated with naringin (10, 20 and 40 mg/kg, respectively) for a period of 56 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days. ISO-induced rats showed a significant (P<0.05) increase in the heart weight, blood glucose, serum uric acid, serum iron and a significant (P<0.05) decrease in the levels of total proteins, A/G ratio and iron binding capacity. A significant (P<0.05) decrease in the activity of Na(+)/K(+) ATPase and increase in the activities of Ca(2+) and Mg(2+) ATPase in the heart and a significant (P<0.05) increase in the levels of glycoproteins in serum and the heart were also observed in ISO-induced rats. Pretreatment with naringin for a period of 56 days exhibited a significant (P<0.05) effect and altered these biochemical parameters positively in ISO induced rats. Naringin also scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2' azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) and nitric oxide (NO) radicals in vitro. Thus, our study shows that naringin has cardioprotective role in ISO-induced MI in rats. PMID- 17289243 TI - Do trauma teams make a difference? A single centre registry study. AB - OBJECTIVE: To evaluate the association between trauma team activation according to well-established protocols and patient survival. METHODS: Single centre, registry study of data collected prospectively from trauma patients (who were treated in a trauma resuscitation room, who died or who were admitted to ICU) of a tertiary referral trauma centre Emergency Department (ED) in Hong Kong. A 10 point protocol was used to activate rapid trauma team response to the ED. The main outcome measures were mortality, need for ICU care, or operation within 6h of injury. RESULTS: Between 1 January 2001 and 31 December 2005, 2539 consecutive trauma patients were included in our trauma registry, of which 674 patients (mean age 43 years, S.D. 22; 71% male; 94% blunt trauma) met trauma call criteria. Four hundred and eighty two (72%) correctly triggered a trauma call, and 192 (28%) were not called ('undercall'). Patients were less likely to have a trauma call despite meeting criteria if they were aged over 64 years, had sustained a fall, had a respiratory rate <10 or >29 per minute, a systolic blood pressure between 60 and 89 mm Hg, or a GCS of 9-13. In a sub-group of moderately poor probability of survival (probability of survival, P(s), 0.5-0.75), the odds ratio for mortality in the undercall group compared with the trauma call group was 7.6 (95% CI, 1.1-33.0). CONCLUSIONS: In our institution, undercalls account for 28% of patients who meet trauma call criteria and in patients with moderately poor probability of survival undercall is associated with decreased survival. Although trauma team activation does not guarantee better survival, better compliance with trauma team activation protocols optimises processes of care and may translate into improved survival. PMID- 17289244 TI - Arterial base excess after CPR: the relationship to CPR duration and the characteristics related to outcome. AB - OBJECTIVE: We aimed (1) to determine the relationship between arterial base excess (BE) immediately after the restoration of spontaneous circulation (ROSC) and duration of cardiopulmonary resuscitation (CPR) and (2) to ascertain the value of admission BE data as a predictor of mortality in patients resuscitated from cardiac arrest (CA). DESIGN: Retrospective chart review. SETTING: An emergency department of a teaching hospital. PATIENTS: Eighty-seven patients who presented with non-traumatic out-of-hospital witnessed CA between January 2001 and December 2004 in whom arterial blood gas (ABG) analysis was performed within 10 min after ROSC. MEASUREMENTS AND MAIN RESULTS: Individual medical records were reviewed for demographic characteristics; cause of CA; electrocardiogram pattern at the scene; CPR duration; ABG data; outcome (survival to discharge or in hospital death). Significant correlations were observed between CPR duration and BE in all 87 patients (r = 0.51, p < 0.01) and in the 66 non-survivors (r = 0.46, p < 0.01), but not in the 21 survivors. Mean arterial BE in survivors was significantly higher than that observed in non-survivors (-15.3 +/- 5.7 mmol/L versus -19.1 +/- 6.3 mmol/L). Mean CPR duration was 34 +/- 16 min in non survivors and 18 +/- 10 min in survivors (p<0.01). Multivariate logistic analysis showed that significant predictors of survival included cardiac aetiology (odds ratio, 6.3; 95% confidence interval, 1.2-33; p<0.01), ventricular fibrillation at the scene (odds ratio, 7.4; 95% confidence interval, 1.4-39.9; p<0.01), and CPR duration GI (99.85) approximately BMI (99.85)>TIFU (99.80)>TIHHU (99.78)>TIDU (99.77)>>Ni-Cr PI (90.59). Sorption kinetic experiments were performed in order to investigate proper sorption time for Ni(II) removal from wastewater. Batch metal ion uptake capacity experiments indicated that sorption equilibrium reached much faster in case of industrial wastewater samples (480min) in comparison to synthetic wastewater (1440min) using same biosorbent. The kinetic data were analyzed in term of pseudo-first-order and pseudo-second-order expressions. Pseudo-second order model described well the sorption kinetics of Ni(II) onto C. fistula biomass from industrial effluents in comparison to pseudo-first-order kinetic model. Due to unique high Ni(II) sorption capacity of C. fistula waste biomass it can be concluded that it is an excellent biosorbent for Ni(II) uptake from industrial effluents. PMID- 17289259 TI - Modeling of adsorption isotherms of phenol and chlorophenols onto granular activated carbon. Part II. Models with more than two parameters. AB - The adsorption equilibrium isotherms of five phenolic compounds, phenol, 2 chlorophenol, 4-chlorophenol, 2,4-dichlorophenol, and 2,4,6-trichlorophenol, from aqueous solutions onto granular activated carbon were studied and modeled. In order to determine the best-fit isotherm, the experimental equilibrium data were analyzed using thirteen adsorption isotherm models with more than two-parameter; nine three-parameter equations - the Redlich-Peterson, Sips, Langmuir-Freundlich, Fritz-Schlunder, Radke-Prasnitz (three models), Toth, and Jossens isotherms - three four-parameter equation - the Weber-van Vliet, Fritz-Schlunder, and Baudu isotherms - and one five-parameter equation - the Fritz-Schlunder isotherm. The results reveal that the adsorption isotherm models fitted the experimental data in the order: Baudu (four-parameter)>Langmuir-Freundlich (three-parameter)>Sips (three-parameter)>Fritz-Schlunder (five-parameter)>Toth (three-parameter)>Fritz Schlunder (four-parameter)>Redlich-Peterson (three-parameter). The influence of solution pH on the adsorption isotherms of 4-CP was investigated. It was shown that the solution pH has not an effect on the adsorption isotherms for pH